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PMC10000212 | Myctophids, commonly vertical migrators, and partial and non-migrant stomiiforms constitute most of the mesopelagic biomass, and transport organic matter throughout the food web from the surface to the ocean's depths. Both the diet and trophic structure of twenty-nine species of mesopelagic fish collected around the Iberian Peninsula were studied through the analysis of stomach contents, quantifying food items with a high taxonomic resolution. The investigation covered oligotrophic to productive habitats, with sampling stations distributed in five discrete zones of the western Mediterranean Sea and the northeastern Atlantic Ocean. The geographic environmental conditions, migratory behavior, and species-specific body sizes allowed for the identification of some major feeding patterns for these fish communities. The trophic niche of migrant myctophids showed a high overlap, with copepods as the primary prey category. The diet composition of generalist myctophids (e.g., Ceratoscopelus maderensis and Hygophum benoiti) reflected the distinct zooplanktonic communities between zones. Large stomiiforms (Chauliodus spp., Sigmops elongatus) preferred feeding on micronekton, while the smallest stomiiforms (e.g., Argyropelecus spp., Cyclothone spp., Vinciguerria spp.) preyed on copepods and ostracods. Given the relevance of the mesopelagic fish communities for commercially exploited species and, therefore, for maintaining the sustainability of the fisheries' activity in the zones analyzed, the information provided in the present study is essential for a better understanding of the biology and ecology of these species. feeding ecology dietary niche partitioning stomach contents European Commission817806 This research was funded by The European Commission, DG Research. H2020, grant number 817806. The project was registered under the title "Sustainable Management of Mesopelagic Resources" (SUMMER). pmc1. Introduction Mesopelagic fishes (MFs) remain for most of their lives in the ocean twilight zone (200-1000 m depth), which contains more fish than almost any other part of the ocean. Thus, they form the largest biomass of teleosteans in the oceans, mainly composed of small and non-commercial species of the orders Myctophiformes and Stomiiformes. They include diverse families (Myctophidae, Gonostomatidae, Phosichthyidae, Sternoptychidae, and Stomiidae), with myctophids possessing the highest species richness (245 species belonging to 33 genera) and gonostomatids having the highest numerical abundance . Recent studies have estimated the worldwide MF biomass to be around 11-15 Gt , but this estimation is still quite imprecise, and scientists are trying to obtain more accurate approximations to robustly report biomass (e.g., objectives of the European project SUMMER accessed on 1 September 2021) and MEESO accessed on 1 September 2021). The most recent estimates, combining acoustics and modeling, downscaled this number from 3.8-8.3 billion tons to 2.4 billion tons . Interest in mesopelagic fish species has arisen as they may be a potential resource for a new pelagic fishery , contributing to the expansion of fish farming as food . Since 2016, Norway has been developing trial fisheries for mesopelagic fishes, such as Benthosema glaciale (Myctophidae) and Mauloricus muelleri (Sternopthychidae), along the mid-Atlantic Ridge and in the North Sea . Thus far, there has been no interest in collecting regular and extensive data that allows for a deeper understanding of their ecological role (e.g., energy and organic matter transport vectors, carbon sequestration, and food web position) across the oceans, as has been carried out for commercial species. Thus, there is still great uncertainty regarding the biological and ecological characteristics of many species. Moreover, the difficulty in observing their ecological behavior in situ, at depth (feeding patterns, daily rations, and migratory ascension, etc.), or keeping them alive in the laboratory, and the considerable fishing effort needed to capture them in large numbers, among other factors, are some of the reasons why their biological cycle and ecological role remain poorly understood. Most myctophids and some stomiiforms undertake diel vertical migrations (DVMs), moving across the water column like hot air balloons from the epipelagic shallow waters where they feed, to deep and less productive oceanic waters, where they rest and excrete organic matter . Diel vertical migrations render them energy and organic matter conduits between secondary producers and upper trophic level predators such as pelagic fish, marine mammals, and marine birds, connecting the horizontal strata from surface waters to the depths of the oceans, and in some cases, even reaching the bathyal environment . The ecological importance of mesopelagic organisms is attributed to the fact that primary production at depths greater than 200 m is negligible, and deep-living fauna depend, for feeding, on the active transport performed by migratory mesopelagic fish, micronekton, and zooplankton . These migrants are concentrated in specific water column layers: they remain in the epipelagic stratum at night and are associated with deep scattering layers during the daytime. These distribution patterns have been studied and it has been found that there is a strong correlation with the level of light penetration into the water column, although other environmental factors (i.e., temperature and oxygen) also influence their vertical distributions . Moreover, MFs play a major role in the biological carbon pump (i.e., the transformation of CO2 and nutrients into organic carbon that sinks to and decomposes in the ocean's depths), for which they may contribute between 8% and 40% of deep carbon flux, depending on the area . The magnitude of the active flux mediated by these fish has been estimated to be comparable to the gravitational flux , but it is still debated if their contribution is large or small . Their function in reducing CO2 emissions (carbon sequestration) is uncertain because we lack the accurate abundance, feeding rate (gut filling and evacuation), and dietary carbon content estimates. The lack of specific experimental designs focused on obtaining a large collection of MF samples for studying, in depth, their main feeding characteristics and the behavior of each fish species in the mesopelagic community, has resulted in the information being scattered and mostly dedicated to the adult and larval stages versus the transformation and juvenile stages. In addition, the information comes from dispersed locations instead of the study of trophic relationships at the community level. In particular, during transformation (i.e., the transition from larvae to juvenile), fish undergo radical modifications in their morphology and pigmentation, which is associated with changes in their habitat , as well as their feeding habits and trophic niches . The study of feeding habits and their related physiological changes with development is also a gap in the knowledge of the life cycle of these fish that needs to be filled. Moreover, previous analyses have outlined the existence of differences in feeding strategies and the resource exploitation of spatial niches and foraging areas, particularly between migrant and non-migrant species . Mesopelagic fishes vary their feeding strategies and dietary intake as they grow, in association with the development of specific physiological features, morphological variability, or bioluminescent patterns . Some myctophids are mostly defined as generalist zooplanktivores with a diet dominated by mesozooplankton, macrozooplankton, and micronekton . However, when considering the complete mesopelagic fish community, trophic differences within both prey dietary proportions and exploited trophic niches can be identified among the species . Extensive literature has been published on the feeding habits and diets of the most abundant species e.g., , but integrative studies analyzing the different components of pelagic food webs and determining the position of MFs at the community level are very limited, e.g., . The combined analysis of stomach contents and biomarkers such as stable isotopes has allowed for the delineation of feeding guilds for several species of the community. Trophic studies based on mesopelagic species are important for unraveling the functioning of open-ocean ecosystems, since myctophids are likely the greatest zooplankton consumers within the midwater fish assemblage, removing a considerable part of its biomass in some regions, e.g., . The Iberian Peninsula is surrounded by diverse marine ecosystems, from the cold and productive Atlantic waters off the western coast to the oligotrophic and warmer Mediterranean basins. The western Iberian region is affected by annual and seasonal upwelling, and the Gulf of Cadiz is affected by the circulation of the subtropical gyre and currents associated with the continental slope . The Mediterranean Sea is characterized by a long period of vertical water stratification, between May and November, and mixing of the water column for the rest of the year, with winter as the most productive season . There is an exchange of water between the Atlantic and the Mediterranean through the Strait of Gibraltar, with an inflow of well-oxygenated water and nutrients from the Atlantic. It is known that the richness of the MF species in the western Mediterranean is lower than that of those in the northeastern Atlantic , which is partly due to the poor adaptive capacity of the immigrants to the Mediterranean's warmer temperature and its higher salinity (temperature ca. 13.5 degC and salinity ca. 38.5, below 200 m) . The feeding habits of these species in the western Mediterranean (off the Balearic Islands and the Gulf of Lions) and the northeastern Atlantic (e.g., the northern Mid-Atlantic Ridge, Azores, and the Canary Islands) have been studied through the analysis of stomach contents and stable isotopes at the species and community levels, e.g., . These studies found that myctophids have overlapping diet compositions with segregated trophic niches throughout the water column. In addition, they found a variability in feeding times between myctophids, which feed in epipelagic waters at night, and gonostomatids and sternoptychids, which feed intermittently throughout the day near the deep scattering layer. Nevertheless, there are gaps in the knowledge of MF trophic ecology, particularly for species, that inhabit relatively deep waters and exhibit extruded stomachs when sampling nets reach the surface, such as those belonging to the Gonostomatidae, Sternoptychidae, and Stomiidae families. Additional uncertainties include the determination of their daily rations or their feeding guild within the community, among others. The analysis of their diet composition, via two different approaches, and the effect of the environmental factors across species and zones will allow for better insight into the quantitative assessment of feeding habits for trophic model parametrization and fisheries management. Diet compositions and food types in the environment can be modeled in the mesopelagic compartment and can simulate how the food web is driven by environmental variables (temperature and mixing processes, etc.). Fish diets represent an integration of many important ecological components that include behavior, condition, habitat use, energy intake, and intra-specific interactions, allowing for the understanding of the ecological aspects of these fish species, even at the population and community levels. The current study examines the relative importance of food categories in fish diets, both in terms of the abundance of different prey types and of their overall carbon content, which might be a prerequisite for the estimation of ingestion rates. Accurate data on the carbon content ingested by MF are important, since certain prey types might constitute a resource that is not abundantly consumed but has a high nutritional value. Moreover, carbon mass estimations, combined with the information on DVMs, will be useful for building future models of active carbon transport in oligotrophic and upwelling areas mediated by respiration and excretion. The present study aims to: (a) characterize the diet composition of 29 species of mesopelagic fish in terms of prey abundance, prey frequency, and prey carbon content, through indexes of relative importance; (b) distinguish the trophic guilds and feeding strategies among mesopelagic fish; (c) establish comparisons between migrant and non-migrant species; and (d) compare the feeding habits of the species in the contrasting areas surrounding the Iberian Peninsula (the western Mediterranean Sea and northeastern Atlantic Ocean), focusing on their particular environmental conditions (thermal and productive regimes) and the diversity of the zooplankton community. We considered the diet composition of the mesopelagic fish community, and migrant and non-migrant species, from the transformation to adult stages. 2. Materials and Methods 2.1. Study Area Sampling stations were predefined around the Iberian Peninsula within five adjacent zones, all with different environmental conditions and exposed to intense fishing activity. These zones were the Balearic Sea (Bal; general subarea GS5, 38.5deg N; 2.4-2.6deg W) and Alboran Sea (Alb; GS1, 35.9deg N; 3.8-3.9deg W) in the western Mediterranean basin, the pelagic waters off the Gulf of Cadiz (Cad; 36deg N; 8deg W), and Lisbon (Lis; 38.1-38.2deg N; 8-9.5deg W.) and Galicia (Gal; 42deg N; 9.5deg W) in the northeastern Atlantic Ocean . The western Mediterranean is a semi-enclosed basin where the number of mesopelagic fish species is much lower than in large oceans . The Balearic Sea is characterized by an oligotrophic condition, although the winter mixing of the water column allows for increasing productivity in the following months. However, the survey was run during the oligotrophic season, when the nutrients were depleted in the epipelagic layer after the long summer period of stratification . The Alboran Sea is the westernmost Mediterranean sub-basin, connected to the Atlantic Ocean by the Strait of Gibraltar, and is affected by intermittent, enriched deep water upwelling . This enrichment favors the presence of cores with a high phytoplankton and zooplankton abundance , where the biomass of the zooplankton community is larger in the core of the western anticyclonic gyre (WAG). Our sampling roughly corresponds to the core of the WAG, which tends to have a higher zooplankton biomass than along its edges . In contrast, the Lisbon and Galicia Atlantic stations are much more productive, and the zooplankton composition of these zones is very diverse and abundant, particularly during the summer biomass peak . For the Atlantic side, the survey took place at the end of the western Iberian Peninsula upwelling season . 2.2. Sampling Fish samples were collected in the Mediterranean Sea and the Atlantic Ocean during the SUMMER survey, run on board the R/V Sarmiento de Gamboa from the 30th of September 2020 to the 18th of October 2020. No commercial species were collected and experiments with living animals were not performed. Fish samples were obtained by using a midwater trawl (Mesopelagos) with a mouth opening of ca. 30 m2, and equipped with a graded mesh, from a 30 mm start to a 4 mm end, and SCANMAR and MARPORT sensors . The midwater trawl was deployed at 26 stations via oblique hauls at 7 depth layers (depth strata: 0-700 m, 700-600 m, 600-500 m, 500-400 m, 400-300 m, 300-200 m, 200-100 m, and 100-0 m) during the day and night to analyze the diversity and vertical migration patterns. The number of specimens analyzed for the present investigation in each zone and their body size ranges are given in Table 1. Ship speed was kept at 2 knots, and the deployment and retrieval speed of the nets was between 10 and 20 m/min. The mesopelagic fishes were sorted, identified on board, and then frozen (-20 degC). All the fish analyzed for the present investigation were measured in the laboratory to the nearest 0.1 mm of standard length (SL) and weighed (wet weight, WW, and eviscerated WW) to the nearest 0.01 g. The environmental factors used for the subsequent analysis, such as the sea surface temperature and integrated fluorescence (first 200 m of the water column), were obtained with an SBE 911 Plus CTD (Bellevue, WA, USA). 2.3. Stomach Content Analyses A total of 349 specimens from the 29 fish species were dissected to examine their stomach contents. The samples from the different stations and layers from the same zones were combined to ensure a minimum number of individuals per species, zone, and developmental stage (usually, 5 juveniles or adults, and 5 in the transformation stage). The minimum sample size established to run the statistical analysis was not reached for Photostomias guernei and Stomias boa; however, the diet compositions of both species were described, providing new information on the prey taxa consumed. For the same reason (small sample size), we considered the juvenile and adult fish stages together hereafter. The selection of individuals was performed by prioritizing night trawls between the depths of 0 and 200 m to ensure that most stomachs were full or contained at least one prey item, considering the premise that most mesopelagic fish migrate to the epipelagic layer to forage near the surface at night . The fishes were thawed, measured for standard length and wet weight, and eviscerated. Afterward, the stomachs were stored in 5% formalin, rinsed, and dissected under stereoscopic microscope for the taxonomic identification of prey items. Each identified prey organism was classified to the lowest taxonomic level allowed by its degree of digestion, then counted and grouped into a functional category. The maximum prey body length and width were measured to the nearest 0.1 mm using a binocular stereoscope (Leica MZ12, Boston, MA, USA) with an ocular micrometric scale. Different reference dimensions, depending on prey taxa, were taken as follows: the standard length for fishes; from the tip of the rostrum to the tip of telson for decapods and euphausiids; from the anterior end of the eyes to the tip of uropods for amphipods; the maximum valve length for ostracods and Bivalvia; the maximum shell length for pteropods; the maximum body length for salps; the trunk length for appendicularians; and the prosome length for copepods. The body dimensions of the identified prey categories were used to estimate the carbon mass, using algorithms compiled from the literature and our own data/calculations (Supplementary Material Table S1). Unlike large commercial fish, mesopelagic species generally prey on tiny organisms that would bias their contribution to the total mass if weighed individually. In these cases, it is desirable to estimate the individual prey weights from direct body length/width measurements using the formulae listed in Table S1. Carbon mass estimations were only carried out when prey items were whole, thus reducing the amount of data available to compare diet compositions in terms of their percentage of carbon mass (%C). For this reason, we did not consider the differences between the zones in this case (except for Myctophum punctatum), and described the main dietary outputs for each species by pooling the individual fish from all zones and obtaining the representative carbon weight proportion for each prey taxa and predator species. Rare prey types were either grouped into more general categories, from genus to family classifications, to increase the sample size, or they were included in a group under the designation of "other categories" (categories with <1% abundance in the diet composition) (see Results). In some stomiiforms, stomach content was mainly represented by particulate organic matter (POM) composed of highly heterogeneous components that varied from one sample to another, and, in some cases, was difficult to identify from the very digested remains. These samples were not used for the estimation of carbon due to the difficulty of estimating the C content of the POM and the risk of introducing a large bias (the composition of the POM cannot be determined). To take into account the presence of POM in stomachs, it was considered as one prey item each time it was detected in a fish stomach. Diet compositions and the importance of each prey category were expressed using different trophic indexes: the percentage frequency of the occurrence of a prey category in the total number of stomachs of a fish species (%F); the percentage number of prey items (%N), the percentage of carbon mass (%C); and two standardized Indexes of Relative Importance (%IRI and %IRIC). The first, %IRI, was calculated as the product of %F per %N, standardized as the percentage of total IRI (%IRI) for each prey item, and the percentage Index of Relative Importance in terms of carbon mass, %IRIC= [(%N + %C)/2] x %F , where %C is the relative contribution of each prey in carbon units, was also standardized as the percentage of total IRIC. 2.4. Statistical Analyses Non-metric multidimensional scaling (NMDS) analysis was used to verify the possible dietary differentiation between species and communities based on the mean prey count per species and zone. This ordination technique shows the distance between the considered objects following a previously calculated dissimilarity based on a Bray-Curtis square root transformed matrix. The goodness of fit of the ordination was assessed by the magnitude of the associated stress value, with a value of <0.2, corresponding to a good ordination . A permutational multivariate analysis of variance (PERMANOVA) with a Type III sum of squares was used to test for significant differences in the prey count among species and various influencing factors. The analytical design was composed of fish species (28 levels; random), zones (5 levels: Bal, Alb, Cad, Lis, Gal; random), the developmental stages nested within the species (2 levels: transformation and adult; fixed), and migratory behavior (3 levels; fixed). The migratory behavior of each fish species was defined as migrators (ascending to the first few meters of the water column), partial migrators (up to 100 m in depth), and non-migrators. A similarity percentage analysis (SIMPER) was applied to identify the mean diet dissimilarity between the developmental stages, between the migrant and non-migrant fishes, and between the individuals of the same species but dissimilar zones when significant. Unidentified material, prey categories accounting for less than 1% of the total diet composition, and empty stomachs were deleted from the prey abundance matrix, where the prey numbers of each taxon were considered per fish. The prey taxa were grouped into genus, family, or order for copepods, by the developmental stages in euphausiids, and into broader taxonomic groups for the remaining prey categories. In addition, cluster analyses were performed to assess the degree of similarity in diets (prey count) between the species for each geographical area. A SIMPROF test defined the significant clusters (p < 0.05). The significant clusters with >40% of similarity were described in the results section. In all the aforementioned tests, the statistical significance was determined by 999 permutations, and all the analyses were performed in Primer-E v6 + PERMANOVA . To ascertain the intra-specific and ontogenetic (transformation and adult stages) differences in prey number, we considered intervals with a minimum of 5 mm SL and at least 3 prey items per size class. Boxplots were built using the ggstastplot package in R . The advantage of this option was that the comparative analyses based on the analysis of variance (ANOVA) and t-tests were also obtained directly. The multivariate diet response of each predator species to the explanatory variables of environmental types (the integrated surface fluorescence between the depths of 0 and 200 m (Fl), the sea surface temperature measured at a 5 m depth (SST), and the temperature at a 450 m depth (T450)) was analyzed using a canonical correspondence analysis (CCA) on a matrix of the mean prey abundances per species and zone. The abundance prey matrix was square root transformed to normalize the data and reduce the heteroscedasticity. CCA is a routine used to perform an ordination of the biological assemblages and environmental variables. This routine is constrained to find the linear combinations between the variables that explain the greatest combination of the data cloud. A forward selection was used to rank the environmental variables and test their significance (p < 0.05). The coordinate scores associated with each axis provide information on how much the variability inherent in the resemblance matrix is explained by each successive axis. The results of the analysis are shown in an ordination diagram, where the length and direction of each vector indicate the strength and sign of the relationship between that explanatory variable and the axes. The CCA was performed with the software Canoco version 4.55 (Ithaca, NY, USA). All the environmental data were obtained from the CTD measurements throughout the water column. The diversity of the prey items in the diets was calculated using the Shannon index (H') and presented as the mean prey diversity per fish species. Only those individuals with at least 50% gut repletion and recognizable prey items were selected for the prey diversity calculations. The prey composition was analyzed here by grouping the species by their vertical migratory behavior, disregarding the zone but not the ontogeny, since even if it is presumed that both the adult and transformation stages of the same species share the same migratory pattern, they might not have the same capability to migrate across the water column and to ingest the same type of prey per size. 3. Results Empty stomachs occurred in 16% of the fish dissected (56 of the 349). A total of 42 prey categories were identified, ignoring the presence of the rare organisms that represented less than 1% of all items in fish stomachs. Copepods were present in the stomachs of most individuals, constituting 19 categories from the 42 identified and occurring in 63% of fish stomachs. Thus, a total 19,136 prey items were identified in the study. Calanoid copepods were the most common prey among myctophids, while they were nearly absent in the stomiid Chauliodus spp. The importance of each prey in the species' diet usually showed great variety, depending on the zone or if it was considered in terms of numerical abundance or carbon weight. The indexes of prey importance are listed in the Supplementary Material Table S2. 3.1. Prey Type 3.1.1. Intra-Specific Variability The nMDS ordination of the fish species according to the mean prey abundances showed a significant segregation of the stomiiforms Cyclothone braueri, C. pygmaea, C. pallida, C. pseudopallida, Chauliodus sloani, Chauliodus danae, and Sigmops elongatus. The myctophid Lampanyctus crocodilus was grouped with C. danae, Photostomias guernei, and S. elongatus, sharing over 50% of their diet compositions, and the myctophids L. alatus, Notolychnus valdiviae, and Lampanyctus pusillus, shared more than 40% of their diet compositions (p = 0.05). The remaining species of myctophids, the two phosyictids, and the three sternoptychids also shared over 40% of their diet compositions. Considering only fish diet similarity among zones , Galicia is the most dissimilar zone (<30% similarity; p = 0.05). However, this dissimilarity is masked by the fact that the number of species collected in this area was low, and they belonged to the stomiiforms Cyclothone spp. and C. danae, which have already been described as having different feeding compositions. Lisbon was also significantly dissimilar from Cadiz and the Mediterranean zones (49% similarity, p = 0.02), the three of which shared >50% similarity (p = 0.05). The PERMANOVA analysis indicated significant differences in the numerical prey abundance among the fish species (Pseudo-F = 4.667, p = 0.001), and for species depending on the zone (Pseudo-F = 2.503, p = 0.001), their development stage (Pseudo-F = 3.9033, p = 0.001), and their migratory behavior (Pseudo-F = 1.887, p = 0.02) (Table 2). At the zonal level, significant differences within species were only detected in some stomiiforms (Argyropelecus hemigymnus, Valenciennellus tripunctulatus, and Cyclothone braueri) and myctophids (Ceratoscopelus maderensis, Diaphus holti, Hygophum benoiti, Lobianchia dofleini, and Myctophum punctatum) (Table 3). The dominant prey categories (>10% diet contribution) exhibited a greater diet dissimilarity between the zones for each species, while the influence of the remaining categories was less pronounced. These dissimilarities were related to the different genus compositions of each zooplankton community. The main differences between the Alboran Sea and the other study zones were due to the consumption of appendicularians. According to the SIMPER analysis, the diet of A. hemigymnus from the Alboran Sea differed from both the Balearic (23%) and Cadiz (18%) zones due to the high contribution of appendicularians in the Alboran zone. The same occurred in the case of C. maderensis and H. benoiti between the Balearic and Alboran zones, in M. punctatum and L. dofleini between the Alboran and Lisbon zones, and within L. dofleini between the Alboran and Cadiz zones (Table 3). Other important feeding differences among fish species and zones were due to the higher consumption of the calanoid copepod Centropages in Lisbon, and also the different contribution of this calanoid to the diet of C. warmingii (17%), L. dofleini (8%), M. punctatum (11%), and V. tripunctulatus (10%) in the other zones (Table 3). Other taxa such as Conchoecia (ostracod) and Pleuromamma (calanoid) were characteristic prey in Cadiz for C. maderensis, D. holti, L. dofleini, and V. tripunctulatus. The differences between the zones could be masked by the variability in fish size of each sample cohort per zone, although this only seemed to occur in L. dofleini, where the individuals that ate euphausiids corresponded to larger SLs, and those that fed on the non-calanoid copepods (Oncaea spp. and Corycaeidae) to smaller SLs. The diet differences between the transformation and juvenile/adult stages were only obtained for A. hemigymnus (p = 0.045) and H. benoiti (p = 0.010) (Table 4). The transformation individuals of A. hemigymnus showed a greater within-group diet similarity (ca. 64%) than adults (ca. 31%), capturing mainly ostracods (Conchoecia spp.) and non-calanoid copepods (Oncaea spp.). In contrast, the adults expanded their diet with appendicularians (19% diet contribution), which might also be influenced by the zone. In H. benoiti, the transformation individuals showed a within-group similarity of ca. 41% due to the consumption of oncaeids and calanoids. The adults also presented a similar variability (38%), feeding on mainly copepods of the genera Pleuromamma and Oncaea. When the analysis focused on the species' migration behavior, significant differences were only detected between the migrant and non-migrant species (t= 1.32, p = 0.007). The dissimilarity between both groups was ca. 85%, with copepods and appendicularians as the most abundant prey in the diets of the migrant fish, although Eucarida (euphausiids and decapods) also influenced this dissimilarity (Table 5). 3.1.2. Community Analyses Individual cluster analyses for each zone were performed to establish the fish diet similarities among species. In the Balearic zone, there was only a significant cluster with low similarity (20%), grouping most of the fish together, and only the myctophids B. glaciale, C. maderensis, and L. pusillus, and the phosichthyid Vinciguerria attenuata, were non-significantly grouped with >80% similarity . This result indicates a high individual variability in the diet composition at the species level, revealing the complexity of the community's food web. A larger number of significant groups were detected in the Alboran Sea. The juvenile and adult individuals of Lampanyctus crocodilus shared a 100% diet similarity; M. punctatum ca. 70%, and C. maderensis and L. dofleini a 60% similarity . Moreover, there was a significant cluster containing the transformation individuals of H. benoiti and the adults of M. punctatum (60% similarity). Finally, M. punctatum, H. benoiti, C. maderensis, and L. dofleini shared a 47% diet similarity. In the Atlantic waters of the Gulf of Cadiz, three significant groups were detected. The transformation individuals of Chauliodus danae and the adults of Cyclothone braueri and C. pseudopallida shared the highest diet similarity at ca. 60%, while the other clusters contained a mixture of species from different families . The classification of the Lisbon samples yielded the highest number of significant groups. The juveniles and adults of the stomiids P. guernei and C. sloani, and the gonostomatid S. elongatus, constituted the cluster with the highest diet similarity (80%). There were also other significant clusters composed of the adults of M. punctatum (78%), L. dofleini (ca. 75%), and C. maderensis and Vinciguerria nimbaria (ca. 55%). In addition, two other significant clusters (>40% diet similarity) were formed by the mixed species of myctophids and stomiiforms . The results for the Galicia zone are not presented here, since the number of samples and species for that zone were underrepresented due to the unfavorable conditions for trawling. There were only fish individuals belonging to the genera Cyclothone and Chauliodus, which is a small representation of the diversity of the mesopelagic fish community. Moreover, the prey contributions to each significant cluster are not described here, as we already described them with the previous SIMPER analysis. 3.1.3. Environmental Influence on Diets The CCA ordination for mesopelagic fish diets explained 26% of the total variance of the fish diet-environment dataset. The relationship of the variables T450 and SST with fish diets was significant, while Fl was not (Table 6). The highest contributor to this relationship was T450 (12.6%) and then SST (11.3%). The first canonical axis significantly explained 50% of the species-environment correlation, and the second axis explained 35%. The variable T450 had a negative correlation with both axis 1 (-0.68) and axis 2 (-0.18), showing that the higher temperatures at a 450 m depth (ca. 13.4 degC) explained the diet of the Alboran fishes and the abundance and presence of cladocerans and appendicularians in their stomachs . A lower T450 level (11.3 degC) correlated with the stomiiforms from Galicia that contained a small number of individuals with a differential contribution of undetermined gelatinous prey in C. pallida. The sea surface temperature (SST) was also negatively correlated with axis 1 (-0.55), but positively correlated with axis 2 (0.35), explaining that the higher mean surface temperatures (23-24 degC) were related to the diet of the myctophids and stomiiforms from the Balearic Sea (with Pleuromamma, non-Calanoida, and Ostracoda as important prey), while the lowest SSTs (ca. 17-18 degC), characteristic of the highly productive Lisbon zone, explained the diet of both myctophids and stomiiforms, with Centropages and Candacia spp. as the main prey. 3.2. Prey Number The mean number of prey items (PN) for myctophids (29.9 +- 12.4) was significantly higher (Kruskal-Wallis chi-squared = 16.06, df = 1, p = 6.137 x 10-5) than for stomiiforms (22.3 +- 7.32). The PN per fish was greatest in M. punctatum (486 prey items in an adult with an SL of 34 mm), and the maximum number of taxonomic categories, identified to the lowest taxonomic level, was observed in L. dofleini (20 different taxa in an adult with an SL of 27 mm). The highest mean PN per stomach was found in the adults of the myctophid species M. punctatum (123 +- 117), L. dofleini (29 +- 28), and C. maderensis (19 +- 29), and both the transformation and adult individuals of H. benoiti (47 +- 56 and 19 +- 2, respectively) (Table S3). Due to the low number of individuals analyzed by size class, no significant intra-specific differences were detected, except for H. benoiti (t-test = -2.68, p = 0.02), which included the transformation stages (<18 mm). Nonetheless, a great variability and low PN values were observed by size class in stomiiforms such as A. hemigymnus and C. braueri , whereas V. nimbaria showed a noticeable increase in PN in larger specimens. A negative trend in the mean PN with size class seemed to occur in C. warmingii, L. dofleini, L. pusillus, and M. punctatum. In contrast, an increase was suggested for C. maderensis and D. holti. The species with the highest mean prey diversity (H' = 1.5-2.0) was L. dofleini for all four zones (Table S3). Some fish species such as B. suborbitale, C. warmingii, M. punctatum, and V. nimbaria attained H' values ranging from 1.5 to 1.8, likely reflecting the zonal diversity of the available prey. 3.3. Diet Composition 3.3.1. Geographic Analysis For most MFs, their diet compositions were more varied in the prey taxa in the Atlantic than in the Mediterranean. In the Balearic zone, calanoids represented 59%N (46%N were Pleuromamma), 47%, and 46%N of the diet of the myctophids D. holti, H. benoiti, and L. dofleini, respectively. Among the stomiiforms, the V. attenuata also fed predominantly on calanoids (62%N, of which 26% were Pleuromamma). Small copepods (cyclopoids), mainly comprising the genera Oncaea, Corycaeus, and Farranula, were the most abundant prey items for the myctophids H. benoiti (34%), C. maderensis (26%), and D. holti (15%), as well as for stomiiforms such as C. sloani (61.5%), V. nimbaria (46%), and A. hemigymnus (24%). Ostracoda was the second most abundant prey item in the Balearic Sea for the species A. hemigymnus (31%), V. attenuata (26%), and V. nimbaria (25%). Euphausiids represented 18% in both D. holti and L. dofleini. (Table S2). In the Alboran zone, appendicularians were the most abundant prey type for the myctophid species M. punctatum (95%), H. benoiti (70%), C. maderensis (57%), and L. dofleini (23%), and for the sternoptychid A. hemigymnus (32%). Calanoids were important for D. holti (58%, of which 48.5% were Pleuromamma), B. glaciale (47%), L. dofleini (39.2%), and L. pusillus (Balearic and Alboran zones together equaled 27%, of which 20% were Pleuromamma), and for the small-sized sternoptychids A. hemigymnus (52%) and M. muelleri (28%). Other abundant prey included cyclopoids for D. holti, B. glaciale, and M. muelleri (21%, 18%, and 39%, respectively). Euphausiids were important for S. elongatus (37.5%) and constituted nearly 50%N of the diet of Lampanyctus crocodilus from the Balear and Alboran zones (both zones were considered together in this case, because the species sample size per zone was low). The Gulf of Cadiz seemed to be the zone with the highest prey diversity, as reflected in the fish diets consisting of a mix of various prey in similar proportions, instead of the dominance of particular prey items, except for the genus Lampanyctus. Specifically, Lampanyctus alatus and L. pusillus had diets based mainly on the calanoid copepod Pleuromamma (63% and 47% N, respectively) and euphausiids (13% in both species). Both prey categories are vertical migrants that perform displacements all throughout the water column, increasing the likelihood of prey-predator encounters. Copepods were represented in the diets of all fish species, with the most preyed upon categories being the migratory, larger-sized calanoids Pleuromamma and Euchaeta in N. valdiviae (75% and 12.5%, respectively), the calanoids in B. suborbitale, D. holti, Cyclothone pseudopallida, and C. braueri (62%, 22%, 60%, and 37.5%, respectively), and the non-calanoids in L. dofleini (cyclopoids comprised more than half of its diet, at 54%), and Argyropelecus sladeni (21%). Unlike the Mediterranean, ostracods were particularly important in A. hemigymnus, C. warmingii (19% in both species), D. holti, Hygophum reinhardtii, and L. dofleini (ca. 15% for each of them), and appeared in the stomachs all the fish species in the Gulf of Cadiz aside from L. alatus. In A. hemigymnus, apart from Ciliophora (a taxon not usually reported as part of its diet, but reaching up to 38%N in one adult individual) and ostracods, cyclopoids were the next most abundant food item (10%). Ceratoscopelus warmingii and D. holti had diverse diets, with tunicates (appendicularians and salps) constituting 40% and 31% N, respectively (Table S2). In the Lisbon zone, calanoids and ostracods were, in general, the most abundant prey items in the diets. Ostracods represented relative abundances of 60% for A. hemigymnus and 14% for both C. braueri and H. reinhardtii, while calanoids represented 83%, 75%, 76%, 65%, 38%, and 20% for L. pusillus, N. valdiviae, L. dofleini, C. warmingii, H. reinhardtii, and L. alatus, respectively. The genus Centropages represented more than a third of the diet of L. pusillus and C. warmingii, and 25%, 23%, and 16% of the N. valdiviae, H. reinhardtii, and L. dofleini diets, respectively. Cyclopoids were more abundant in small and medium-sized stomiiforms (C. braueri: 57%; and A. hemigymnus: 20%) and were also found in small-sized myctophids such as H. reinhardtii, C. warmingii, L. dofleini, and L. pusillus (Table S2). The euphausiid abundance in L. alatus and L. pusillus diets (20% and 7%, respectively) was similar to that observed in the Gulf of Cadiz. Cyclothone spp. and C. danae were the only species analyzed in Galicia. Cyclothone braueri fed on calanoids (50%) and C. pallida on appendicularians (70%), while the stomachs of C. danae contained decapods (40%) and POM (40%). Considering a prey's relative importance to be >10%IRI, copepods had a high importance in the fish diets of all five studied zones, with calanoids more abundant in larger specimens and cyclopoids in smaller-sized ones. Appendicularians were particularly important for some species (C. maderensis, C. warmingii, D. holti, H. benoiti, L. dofleini, M. punctatum, and A. hemigymnus) in the Alboran Sea. Euphausiids, however, were linked to species-specific preferences in L. crocodilus (89% IRI) and S. elongatus (91%), which are large-bodied fishes. Ostracods were the most important prey category consumed by A. hemigymnus in the Balearic and Atlantic sites (Balearic: 57.5%; Cadiz: 67%; and Lisbon: 48.5%) and by Argyropelecus sladeni in Cadiz (34%), indicating that ostracods are the prey of choice of this genus. In contrast, the presence of ostracods was important in C. warmingii (33%), D. holti (27.5%), and L. dofleini (17%) in Cadiz. It is plausible to think that the differences between both Atlantic zones (Cadiz and Lisbon) could be addressed by the differences in the fish size range. 3.3.2. Species Diet Composition in Terms of Carbon Content Among myctophids, calanoids and euphausiids dominated the diet contributions in terms of their carbon content, with different proportions depending on the species. The differences between the congeneric species from the different zones were very noticeable. For example, the diet of B. glaciale from the Mediterranean Sea was dominated by calanoids (78% C and IRIC), while the genus Candacia constituted 65% of the estimated carbon mass, followed by euphausiids (20% C and 10% IRIC) . In contrast, the B. suborbitale inhabiting Atlantic waters preyed on small mesopelagic fish, which were by far their most important dietary item in terms of carbon (84% C and 36% IRIC). The diet of C. maderensis (Mediterranean Sea) was composed mainly of fish (53% C and 7.7% IRIC) and tunicates (appendicularians) (23% C and 44.6% IRIC), whereas calanoids (mainly Centropages, 19% C, and Pleuromamma, 11% C) constituted 40% C (53% IRIC) of the diet of C. warmingii (Atlantic waters), followed by euphausiids at 23.6% C (4.3% IRIC), ostracods (13.5% IRIC), and tunicates (15.4% IRIC). The diet of H. reinhardtii (Atlantic waters) differed from that of H. benoiti (Mediterranean Sea), mainly in its diversity and proportions of calanoids (87% vs. 33% C and 72% vs. 13% IRIC), particularly of the genera Candacia and Centropages consumed by H. reinhardtii. Finally, L. alatus and L. pusillus showed a similar diet, independent of the zone, mainly based on euphausiids (92% C and 43.5% IRIC; and 60% C and 29% IRIC, respectively), whereas fish constituted most of the dietary carbon in L. crocodilus (96% C and 27.3% IRIC). In D. holti, euphausiids (77% C and 27% IRIC) and gelatinous prey (12% C) were important in their diet. In Lepidophanes gaussi, Pleuromamma represented 68% C (81% IRIC) and Candacia represented 23% C (4% IRIC). Euphausiids and calanoids (mainly Candacia and Pleuromamma) constituted 51% C (30.3% IRIC) and 38% C (40.4% IRIC) of the diet of L. dofleini. No dissimilar diet composition was noted at a local scale in M. punctatum, which was dominated by tunicates (12.5% C and 26.2% IRIC) and calanoids (79% C and 63.4% IRIC) . Stomiiforms showed contrasting prey preferences. Large-bodied species such as C. danae, S. elongatus, and C. sloani preyed on large crustaceans, including decapods (99% C and 42% IRIC), euphausiids (97% C and 96% IRIC), and fish (92.5% C and 72.5% IRIC), respectively. Small-bodied species such as A. hemigymnus, A. sladeni, M. muelleri, and V. tripunctulatus commonly ingested calanoids (11-95% C) and ostracods (4-36% C), although gelatinous prey (72% C and 27% IRIC) were also important for A. hemigymnus. A similar pattern was also recorded for V. attenuata (63% C and 77% IRIC for calanoids; and 36% C and 19.5% IRIC for ostracods), whereas V. nimbaria fed mainly on calanoids (85% C and 60% IRIC). Conversely, the genus Cyclothone showed dissimilar diets among congeneric species, in terms of numerical prey abundance . The diet of C. braueri was dominated by copepods, calanoids, and non-calanoids, and that of C. pallida and C. pseudopallida by tunicates and calanoids, respectively. Notably, the stomachs of Cyclothone pygmaea contained mostly dietary remains in an advanced stage of their digestion. Finally, we think it is worth mentioning the presence of a few pieces of plastic in 3 individuals of L. pusillus and P. guernei. We found a pink plastic fiber in L. pusillus, a non-colored plastic fragment in P. guernei, and two plastic fragments (green and black) in the same stomach of another P. guernei. 4. Discussion 4.1. Study Constraints Dietary studies based on stomach contents can have limitations when trying to ascertain trends in the specific feeding strategies of mesopelagic fish, such as myctophids and stomiiforms, or other pelagic fish. The first limitation is the low number of samples per species due to the time-consuming process of prey identification with this classical method. To provide very specific information at the community level and among these communities is a chimera for many reasons, including monetary funding, the time needed for taxonomic identification, and the increasing need to publish research results quickly. This problem inevitably affects the power of statistical analyses and their conclusions. Even more so, differences in diet compositions are caused by many factors that influence resource partitioning, including the range of vertical distribution, migratory behavior, and feeding strategies . Acknowledging these limitations, in the present study, we provide a general idea of the dietary differences among species, which allows us to establish feeding guilds and relate their dietary preferences to the ecological environment. The second limitation, which is directly related to the first one, is the view that intra-specific variability is not relevant. Thus, individuals from the same haul should theoretically have similar prey compositions in their diets, since they are aggregated in the same water stratum. One of the most highlighted issues in the present study is precisely the intra-specific variability between and within the size ranges for many species, far from the regional dissimilarity described for some species. This is not novel , and the problem lies again in the difficulty of providing an accurate picture at the level of community. In this context, our study did not allow for inter-specific comparisons of some species of stomiids, such as Photostomias guernei and Stomias boa, due to the low number of specimens collected (only 4 and 2, respectively). The main reason is that both species inhabit very deep waters, ranging from below a depth of 1000 m to below the epipelagic layer (up to a 100 m depth), and are found in low abundances . There is a great difficulty in sampling deep water species in sufficiently large numbers to have an adequate sample size for statistical analysis. Despite this, we considered that it is advisable to include them to determine their role in the whole mesopelagic fish community. Other issues are related to a lack of consensus regarding the method of quantification and determination of the importance of diet composition. Here, we included a method of reconstructing prey carbon mass, usually using body length, similar to that employed by various authors e.g., . This is an interesting approximation of diet composition in terms of its application to biomass or energy flow, even when some biases need to be assumed with an underestimation of rapidly digested prey items, in contrast to slowly digested ones. Additionally, it is impossible to quantify the contribution of the POM by this method, which is quite important in deep-living species. 4.2. Feeding Guilds Our findings asserted that the principal food for the most common and frequent fish in the mesopelagic assemblage, in both the western Mediterranean and northeastern Atlantic ecosystems, was crustaceans, especially copepods. In general, previous investigations defined these fishes as zooplanktivorous and micronektivorous, filling the role of secondary consumers in pelagic waters . Copepods were by far the most consumed organisms by myctophiforms and some stomiiforms. Nevertheless, the prevalence of small prey in the diets of some fish species in the present investigation may be partly explained by the dominance of small-sized individuals and the lack of the largest adult stages (a constraint of our sampling methodology) . On the other hand, the inter-specific comparison of diet composition is more diverse when the prey items are identified to the lowest taxonomic level and expressed through different indexes (e.g., numerical abundance versus carbon content). Although some species of myctophids are considered generalists, the proportions of the ingested prey taxa varied from one species to another, and there was also a clear dietary shift throughout fish growth. Even so, our findings allow for the delineation of six trophic guilds, where some feeding characteristics and behaviors are shared at the family level, and for the comparisons of these species with the literature . Based on the results of this study and previous investigations , the species of myctophids analyzed can be ascribed to four main trophic guilds (Table 7): zooplanktivorous-mixed crustacean feeders (B. suborbitale and M. punctatum), generalists (L. dofleini, H. benoiti, C. maderensis, C. warmingii, and D. holti), micronektivorous (Lampanyctus spp.), and copepod feeders (B. glaciale, Lepidophanes gaussi, and N. valdiviae). However, some species (e.g., M. punctatum and H. benoiti) showed differences in their diet composition between locations, demonstrating the feeding plasticity of the species. Additionally, the small and medium-sized classes of myctophids (mostly the transformation and juvenile stages) (B. glaciale, C. maderensis, C. warmingii, D. holti, H. benoiti, L. dofleini, L. pusillus, and M. punctatum) fed on large numbers of mesozooplankton prey, whose importance decreased as the fish grew. An exception to this trend was observed in large individuals of D. holti that showed an intake of more nutritious and larger prey, although in lower numbers, indicating a shift towards a more specialized diet. Species-specific feeding preferences for euphausiids were detected in large specimens of L. crocodilus and S. elongatus (89% and 91% IRI, respectively). The larger specimens of Lampanyctus spp. and B. suborbitale fed mainly on micronekton and fish (apparently myctophids or stomiiforms). Some species can decrease their migrations to upper water layers in the adult-senescent phase, as occurs in L. crocodilus , changing their diet from epipelagic crustaceans during the pelagic life stage to fish in the deeper water living stage. The myctophids N. valdiviae and L. gaussi showed similar diets that were almost exclusively based on copepods. Another investigation , however, considered L. gaussi to be a mixed crustacean feeder. In total, two major patterns of feeding can be categorized within the stomiiforms (Table 7): zooplanktivorous for small species, feeding mostly on copepods (Cyclothone spp., M. muelleri, V. tripunctulatus, V. nimbaria, and V. attenuata) and ostracods (Argyropelecus spp.) ; and micronektivorous for larger species (Chauliodus spp., P. guernei, and S. elongatus) that feed on larger and more nutritious prey such as decapods and euphausiids, which, as a consequence, are generally estimated to have a higher trophic level . Furthermore, C. sloani is the only species in which copepods were absent, as it is a specialist feeder (mainly myctophids and other MFs). Moreover, not all the individuals of its population respond synchronously to diel variation in light intensity; thus, it may avoid resource competition with other fish individuals or species and contribute to its niche segregation from other co-inhabitants/mesopelagic species via depth and/or size, or through its specialized feeding on them . The stomiiform species studied here that do not migrate to the near-surface layers are segregated from the myctophids during feeding hours, which prevents direct competition . An interesting aspect that deserves further investigation is the presence of POM detected in the stomachs of the genera Chauliodus and Cyclothone. Finally, the contribution of fish to the diets or the exclusive piscivory of some stomiids and gonostomatids is also a relevant aspect, as they have a completely different feeding pattern to the other mesopelagic fish with a mixed diet, and might act as upper trophic level predators in the mesopelagial realm . 4.3. Comparison of the Diet Composition of Mesopelagic Species among Zones Factors such as the selection of specific prey items by fish predators, the vertical distribution ranges of consumers and their prey, and the migratory behaviors of these fish may contribute to a reduction in competition for the available resources . Among the myctophids studied here, L. dofleini showed great voracity (a high number of prey items in the stomach) and the highest diversity of prey categories in all the studied zones, revealing its non-selective and generalist feeding strategy. Additionally, M. punctatum, H. benoiti, and C. maderensis were quite voracious species. Specifically, M. punctatum attained a higher prey diversity in Atlantic waters (Lisbon), whereas H. benoiti and C. maderensis did so in the Mediterranean Sea (Balearic and Alboran zones, respectively). Nevertheless, M. punctatum and H. benoiti shared a highly similar diet composition (>66% similarity in Alboran), as did M. punctatum and L. dofleini (>40% in Lisbon). The fact that these species had a high prey diversity in their stomachs in different zones, and that they also shared a large portion of their diet compositions, suggests a certain adaptive intra-specific flexibility in their foraging behaviors (i.e., active feeding, dietary shifts depending on the regional or seasonal zooplankton availability, and generalist/facultative feeding), which might favor their survival, thus attaining them higher biomasses within myctophid communities . For instance, M. punctum fed on calanoids, mainly from the genera Euchaeta and Centropages, in the Lisbon zone, and it preyed mainly on appendicularians in the Alboran zone. Additionally, a high prevalence of appendicularians has been reported for the specimens from the Strait of Messina in the central Mediterranean . The environmental conditions in each zone may also act as a filter, preventing the competition by MFs over the same resources (the 'niche filtering hypothesis'; ). Nevertheless, predator-prey interactions are inherently size-dependent, and they also act as a factor limiting the overlapping of trophic niches . A clear example of this relationship is the different patterns found linked to the ontogenetic shift: B. glaciale, C. maderensis, D. holti, and H. benoiti ingested a smaller number of prey items in the medium-sized classes than in the larger ones. Regarding the ingested number of prey, the following species deserve special mention: C. warmingii showed an inverse model (smaller prey items in larger fish); the largest adults of L. dofleini and L. pusillus showed a noticeable decrease in the number of prey but a feeding preference for decapods, euphausiids, larger calanoids (Euchaeta, Centropages, or Pleuromamma), and even fish; and the transformation individuals of M. punctatum were unusually voracious. Among the stomiiforms, the non-migrant Cyclothone was the most abundant genus in our study , and the one with the highest numerical abundance in the twilight zone, although the Cyclothone species do not interact with the migratory species during feeding hours . There was geographical segregation of some of the Cyclothone species studied here, i.e., C. pygmaea is only distributed in the Mediterranean, while C. pallida and C. pseudopallida do not occur in Mediterranean waters , avoiding the congeneric competition for trophic resources. This congeneric competition may also be avoided to a certain degree by vertical segregation. In the Mediterranean Sea, C. braueri has a shallower distribution (mainly at 400-500 m) than C. pygmaea (600-700 m) , and in the Atlantic, C. braueri has a shallower distribution than C. pallida (500-600 m), although it partially overlaps with C. pseudopallida (400-600 m) . The diets of the Cyclothone species showed the lowest diversity among all the mesopelagic fish studied (small copepods and ostracods), and the number of prey consumed was usually limited to one or two (55% vacuity), except for the largest species, Cyclothone pallida, for which up to 26 prey items were found in the stomach. In general, the estimated amount of the diet carbon content is quite low for all the species. The other gonostomatid, S. elongatus, and the two sternoptychids, A. hemigymnus and A. sladeni, which feed on zooplankton, also segregate their foraging area with the near-surface migratory myctophids, as they only migrate up to 100 m (vertical spatial segregation). Some species such as A. hemigymnus can also feed during the daytime , thus reducing their interaction with the nocturnal mesopelagic predators while foraging. Studies based on isotopic signatures detected that the migrant fishes feeding on copepods were clearly distinguished from the partial and non-migrant copepod feeders, showing that the food web baseline differs between the epipelagic environment and deeper waters . The carbon content contribution of the prey items to fish diets is key to better understanding pelagic ecosystems. Certain prey types can constitute a resource that is not abundantly consumed, but has a high nutritional value, likely leading to a decrease in the predator's daily rations. Among the crustacean prey categories, the importance of each taxon in mesopelagic fish diets was contrasted when comparing their numerical abundance with their carbon mass. For instance, calanoid copepods usually dominated in the diet compositions of stomiiforms and myctophids in terms of the number of items ingested. However, larger crustaceans such as euphausiids and decapods constituted most of the estimated carbon weight in the larger-sized predators, as occurred in stomiiforms such as C. danae and S. elongatus, and myctophids such as L. dofleini, D. holti, and Lampanyctus spp. Another example is the migratory calanoid Pleuromamma, which is consumed in large numbers and constituted the major carbon bulk of myctophid copepod feeders such as L. gaussi and N. valdiviae, as well as stomiiforms such as V. attenuata, V. tripunctulatus, and Maurolicus muelleri. This calanoid is a vertical migrant that performs displacements all across the water column, which might increase the likelihood of prey-predator encounters. The most visible difference between the feeding patterns based on the prey carbon weight and the prey numerical biomass was found in the micronektivorous species of stomiids, and the largest adults of the Lampanyctus spp. These species fed on lower numbers of prey but showed a shift in the selection of large crustaceans (decapods or euphausiids) and fish with a higher carbon content. Lampanyctus crocodilus and L. pusillus from the western Mediterranean Sea preferred euphausiids . In particular, the more advanced adult stages of L. crocodilus have been reported to decrease their migratory displacements to the epipelagic layer and remain near the benthic domain, where they feed on these larger prey . The occurrence of copepods in the diet of myctophids and stomiiforms had a lower importance in terms of carbon, indicating that other prey categories were more important and contributed higher biomasses to their diets. We have mentioned the most evident difference in micronektivorous species, but other prey categories, for example, such as tunicates and other gelatinous organisms, were important in terms of their carbon weight (74% C) in the diet of A. hemigymnus. In this case, the tunicate-based diet of this sternoptychid is related to the peak occurrence of appendicularians in Alboran and Cadiz during the study period, although usually its diet is dominated by copepods and ostracods . In most dietary studies of mesopelagic fish, the contribution of particulate organic matter (POM) could not be quantified through stomach content analysis, although its presence was evident in Cyclothone spp. Although we were not able to assign any carbon weight to the POM, we accounted for the number of times that the POM appeared in the diet of a species (as a "prey" individual/item itself), and thus, %N, %F, and %IRI could be obtained. Usually, POM includes detritus and marine snow, and constitutes a nutritive resource in deep ocean waters for mesopelagic fish , especially for small fishes such as Cyclothone spp., which play an important role in the remineralization of organic carbon at depth . 4.4. Influence of Zone Patterns The environmental characteristics of each zone (e.g., the temperature, fluorescence, and zooplankton availability) influenced the fish diet composition, but other factors such as migratory behavior or individual body size might be masking the geographical influence. The highest values of fluorescence were found in Lisbon and Galicia, and to a lesser extent in Alboran. The highest temperatures were found in the two Mediterranean zones. The highest productivity of the upwelled influenced zones likely resulted in a higher zooplankton abundance, in turn enhancing the prey availability in these zones versus the more oligotrophic ones. For instance, in the productive Atlantic zones, the mesopelagics L. dofleini and Vinciguerria spp. had larger numbers of calanoid copepods, mainly represented by the genera Centropages and Clausocalanus/Paracalanus, than in the oligotrophic ones. This coincides with the results of a study during the late summer in the northwestern Atlantic off the Portuguese coast , where copepods were reported as forming >80% of the mesozooplankton community, with these species being among the most numerically abundant. The higher temperatures in the Mediterranean zones can be related to the presence of the cladoceran Penilia avirostris in the diet of several myctophids from Alboran, whereas these prey organisms were not found in Lisbon fishes. The diet compositions (identifying prey to the lowest taxonomic level) of the myctophids from Cadiz and Lisbon were more dissimilar to each other than to those from Alboran, which overlapped with the fish diets of the Balearic and Cadiz zones. The diversity of the zooplankton from Alboran is generally higher than those in eastern parts due to the influence of the Atlantic, and might have a species composition intermediate between that of the Gulf of Cadiz and the Balearic Sea. In general terms, there were more between-species dissimilarities in the myctophid diets from the Balearic Sea, which were more similar to the diets of the species from different zones. This might indicate that fish species have a strategy to avoid competition among themselves in the Balearic Sea, as it is the most oligotrophic studied zone, and might have a lower abundance of available food resources. The role of appendicularians in the diet also deserves comment. Appendicularians seemed important in the diet of the specimens captured in the Alboran zone (A. hemigymnus: 42.5% IRI; C. maderensis: 25% IRI; H. benoiti: 76% IRI; and L. dofleini: 23% IRI) and, to a lesser extent, in the species from the Gulf of Cadiz (C. warmingii: 25% IRI; and D. holti: 19% IRI). This fact might indicate that, during the study period, appendicularians were abundantly present in the zooplankton and were selected by some of the mesopelagic species (C. pallida), or captured by the generalist ones (e.g., H. benoiti or C. maderensis). Moreover, the consumption of appendicularians by these predators might suggest that they have higher trophic levels in the more productive zone of Alboran than in the oligotrophic Balearic Sea, where the baseline of the trophic web could be represented by copepods (in diets, mainly of Pleuromamma spp.). Cladocerans were numerically important in C. maderensis, L. dofleini, and H. benoiti in Alboran, which supports the idea that these species are generalist feeders that prey on a large number of organisms that present dominant biomasses in the environment, such as cladocerans that display strong population increases under favorable conditions , particularly Penilia avirostris during the summer-autumn period in Alboran . Cladocerans are epipelagic prey whose populations increase quickly under the favorable conditions of summer in the area. There is interest in returning to classical studies based on stomach content analyses to complement isotopic and molecular data. Either of these two techniques is good for establishing numerical relationships, with the calculation of the biomass consumed by these mesopelagic species. Moreover, there are other limitations to our current knowledge of the trophic ecology of MFs, as several traits remain unevaluated (e.g., How many hours does a predator stay in the feeding zone? How many times a day does it feed? Why do the different predator species of MFs feed on different functional groups? What is driving these differences?). To allow for assumptions about the functioning of pelagic ecosystems and to define accurate trophic models, quantitative data on predatory pressure and the contribution of mesopelagic fish to carbon cycling through dietary intake are of relevance. Evaluating the predation impact of the mesopelagic assemblage on zooplankton remains an issue to be addressed, as it needs information on the individual feeding rates of species, which are nowadays mostly lacking. The fishing grounds of the Iberian area have been intensely exploited. Mesopelagic fish are also food for commercially exploited species (e.g., tuna, hake); thus, to maintain the sustainability of fisheries' activities, it is also essential to design strategies for the protection and sustainable assessment of mesopelagic fish communities. The present study was carried out in important fishing areas, corresponding to different geographical subareas (GSA) of the Mediterranean basin (GS5. Balearic Islands; and GS1. The Alboran Sea) and the FAO fishing subarea 27.9.a (the Gulf of Cadiz, the waters off Lisbon, and Galician waters), and thus, the information provided in this study might be potentially useful for evaluating the future protection strategies of these fishing areas. 5. Conclusions Trophic studies on the mesopelagic fish community require a better understanding of species-specific feeding behaviors, well-planned experimental design, and high investment to be able to focus on the effect of the diverse factors that affect the community, since usually, there are many elements modulating mesopelagic fish feeding behavior: some species or individuals, depending on their ontogenetic development, are prey selective, or, on the contrary, are quite voracious, and consume a broad diversity of prey (e.g., L. dofleini and M. punctatum). We also found species with adaptive intra-specific flexibility in their foraging behavior (e.g., active feeding, a change of diet as a function of the regional or seasonal variability of zooplankton, and a large range of prey resources, etc.). The diet composition of generalist myctophids such as Hygophum benoiti and Ceratoscopelus maderensis reflects the different zooplanktonic communities among the zones. Moreover, geographic environmental conditions, migratory behavior, and body size are all factors that condition fish diets and allow for the identification of some major feeding patterns among these mesopelagic fish communities. The trophic niche of migrant myctophids showed a high overlap, with copepods as their primary prey category. The large stomiiforms (Chauliodus spp., Stomias boa, and Sigmops elongatus) preferred feeding on micronekton, while the smallest stomiiforms, Cyclothone spp. and Argyropelecus spp., preyed upon copepods and ostracods. Given the relevance of the mesopelagic fish communities to commercially exploited species and the maintenance of the sustainability of fisheries in the studied regions, the present study provides important information for a better understanding of the ecology of these species. Acknowledgments The authors thank the crew and scientists on board the research vessel "Sarmiento de Gamboa" and the technicians of the "Unidad de Tecnologia Marina" (UTM) for their support in the collection of oceanographic data and biological samples during the survey cruise and for the sorting and preparation of the samples. This work also acknowledges the Severo Ochoa Centre of Excellence accreditation (CEX2019-000928-S). Supplementary Materials The following supporting information can be downloaded at: Table S1: Length-weight relationships for specific prey taxa and their carbon mass estimations as a percentage of body dry weight. Source indicates the bibliographic reference used for the calculation of DM and CM. Locations 1 and 2 refer to the geographic areas of study, of the literature cited, for DM and CM relationships, respectively. DM: dry mass; CM: carbon mass; WM: wet mass; L: body length; SL: standard length; TL: total length and trunk length in the case of appendicularians; V: volume; W: body width. Own data: in this case, the measurements obtained from mesopelagic fish from previous survey cruises (Migrants and Active Flux in the Atlantic Ocean project, MAFIA; CTM2012-39587-C04-03)) , Table S2: Diet composition of myctophids and stomiiforms in terms of prey number, abundance (%N), frequency of occurrence (%F), and index of relative importance (%IRI). Cells with zeros indicate the absence of data, Table S3: Mean Shannon diversity index (H') and mean prey number per fish species. Click here for additional data file. Author Contributions M.P.O. conceived and promoted this study and acted as survey cruise leader. A.B. conducted the stomach content analyses and prepared the data for exploratory analysis and statistical treatment. Conceptualization, A.B. and V.M.T.; methodology, A.B.; formal analysis, A.B., M.P.O. and V.M.T.; investigation, M.P.O.; resources, M.P.O.; data curation, A.B. and V.M.T.; writing--original draft preparation, A.B.; writing--review and editing, V.M.T. and M.P.O.; visualization, A.B. and V.M.T.; supervision, M.P.O. and V.M.T.; project administration, M.P.O.; funding acquisition, M.P.O. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement This work was conducted in accordance with the provisions of the Royal Decree 53/2013, "de 1 de febrero, por el que se establecen las normas basicas aplicables para la proteccion de los animales utilizados en experimentacion y otros fines cientificos, incluyendo la docencia" (implemented by the European legislation on the use of animals described in Directive 2010/63/EU of the European Parliament and the Council of 22 September). The research involved vertebrate animals that are not endangered species. This legislation excludes the need to ask for specific permits for the collection of the mesopelagic and bathypelagic species that were used in this project. In addition, the collection of these species during the authorized survey cruise had previously been justified in the preceding European-granted project "SUMMER" (Grant agreement No: 817806). No research element intended for the project harmed the environment. Informed Consent Statement Not applicable. Data Availability Statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Figure 1 Map of the Iberian Peninsula, surrounded by the western Mediterranean Sea and the northeastern Atlantic Ocean, showing the five sampling areas (Bal: Balearic Sea; Alb: Alboran Sea; Cad: Gulf of Cadiz; Lis: off Lisbon; and Gal: off Galicia). Red diamonds indicate trawling stations with Mesopelagos nets. Figure 2 (a) Two-dimensional nMDS ordination plot of mesopelagic fish based on prey abundance (%N) and Bray-Curtis distances. Symbols refer to fish orders: triangle: Myctophiformes; and square: Stomiiformes. Colors refer to the 5 fish families: Ster: Sternoptychidae; Myct: Myctophidae; Cyc: only the genus Cyclothone within Gonostomatidae; Sto: Stomidae; Gonos: Gonostomatidae; and Phos: Phosycthidae. The species names have been abbreviated using the first three/four letters of the binomial scientific name (e.g., Myctophum punctatum has been shortened to Myc punc). (b) Two-dimensional nMDS plot based on %N and Bray-Curtis distances among zones. The similarity in the diet of species was established at >=50% and depicted by solid green circles, and >=60% by dotted blue circles. Figure 3 Four dendrograms showing significant groupings for fish diets in each zone, apart from Galicia, after applying cluster analyses to the Bray-Curtis similarity and transformed matrixes of prey abundances. Significant clusters are denoted by colored symbols and black lines (SIMPROF, p = 0.05). Dashed lines depict non-significant clusters. Labels indicate the shortened name of the species (first three/four letters of the genus and species) and the developmental attribution: T: transformation; and A: adult (including juveniles). Zones: (a) Balearic; (b) Alboran; (c) Cadiz; and (d) Lisbon. Figure 4 Canonical ordination plot (CCA) for the diet of mesopelagic species. The red arrows indicate the explanatory variables (SST: sea surface temperature; T450: temperature at the 450 m-depth strata; and FI: integrated fluorescence in the first 200 m of the water column). Labels with two or three letters indicate the species name, and the separated upper-case letter indicates the zone (B: Balearic; A: Alboran; C: Cadiz; G: Galicia; and L: Lisbon). Ah: A. hemigymnus; BG: B. glaciale; Bs: B. suborbitale; Cb: C. braueri; Cp: C. pallida; Cps: C. pseudopallida; Cm: C. maderensis; Cw: C. warmingii; Chs: C. sloani; Dh: D. holti; Hb: H. benoiti; Hr: H. reinhardtii; Lc: L. crocodilus; Lp: L. pusillus; Ld: L. dofleini; Mm: M. muelleri; Mp: M. punctatum; Nv: N. valdiviae; Va: V. attenuata; Vn: V. nimbaria; and Vt: V. tripunctulatus. Figure 5 Boxplots for each mesopelagic species showing mean prey number versus standard length (SL (mm)). The line in the box indicates the median value of the data and the upper and lower edges of the box, and the first and third quartiles, respectively. The whiskers extend to 1.5 times the interquartile range. The points outside the ends of the whiskers are outliers. The ticks on the X-axis indicate the end of the size interval for each species. Boxplots for the species are displayed in alphabetic order. Figure 6 Diet compositions of Myctophiformes and Stomiiformes, pooling individuals of the five zones studied by fish species and expressed as a percentage of carbon content (%C) and percentage of abundance (%N). Prey taxa were reduced to 20 categories; "Other categories" represents <1% N. The names of the fish species are abbreviated as the first three letters of each word of the binomial scientific name. animals-13-00886-t001_Table 1 Table 1 Summary of fish samples examined for stomach content analyses from the Mediterranean and Atlantic regions selected for the study. Migr: migratory behavior (VM: vertical migrant; PM: partial migrant; and NM: non-migrant); SL: standard length (mm); T: transformation stage; A: adult stage; and N st: number of analyzed stomachs. Sampling zones: Bal: Balearic; Alb: Alboran; Cad: Gulf of Cadiz; Lis: Lisbon; and Gal: Galicia. Species Migr Region Size Range (SL, mm) N st N with Prey Stomiiformes Gonostomatidae Cyclothone braueri NM Mediterranean Bal A: 23 5 5 Alb A: 16.50-23.50 5 4 Atlantic Cad A: 24-25 10 6 Lis A: 16-33 10 9 Gal A: 26-27 5 5 Cyclothone pallida NM Gal A: 32-52 12 8 Cyclothone pseudopallida NM Atlantic Cad A: 20-35 5 4 Lis A: 18-26 5 5 Gal A: 28 1 1 Cyclothone pygmaea NM Alb A: 18-35 5 5 Sigmops elongatus PM Atlantic Cad A: 116-140 6 6 Lis A: 106-125 5 4 Sternoptychidae Argyropelecus hemigymnus PM Mediterranean Bal T: 7-16.2 5 5 A: 22-27 3 3 Alb A: 20-35 11 11 Atlantic Cad A: 21.5-43 4 4 T: 9-14.5 4 4 Lis A: 18-31 4 0 Argyropelecus sladeni PM Cad T: 7-11 5 5 Maurolicus muelleri PM Alb T: 13-15 4 4 A: 16-26.5 6 6 Valenciennellus tripunctulatus NM Atlantic Cad A: 18.5-24.5 5 5 Lis A: 23-27.5 4 4 Phosichthyidae Vinciguerria attenuata VM Bal T: 16.5-19 5 5 Vinciguerria nimbaria VM Atlantic Cad T: 15-17.5 5 5 A: 26-33 5 5 Lis T: 16-23 5 4 A: 23.5-35.5 6 6 Stomiidae Chauliodus danae VM Atlantic Cad T: 28.5-38 5 3 A: 73-123 5 5 Gal A: 97-116 5 5 Chauliodus sloani VM Mediterranean Bal A: 61-73 3 2 Alb A: 200 1 1 Atlantic Cad A: 40-113 5 5 Lis A: 43-123 7 7 Photostomias guernei PM Lis A: 63-72 4 4 Stomias boa VM Cad A: 64-123 5 2 Myctophiformes Myctophidae Benthosema glaciale VM Mediterranean Bal T: 17.5-20 5 5 A: 22-29.5 5 5 Alb A: 31-32.5 5 5 Benthosema suborbitale VM Atlantic Cad A: 20-29 5 5 Lis A: 27 1 1 Ceratoscopelus maderensis VM Mediterranean Bal T: 16.5-18.5 5 5 A: 21-44 5 5 Ceratoscopelus warmingii VM Atlantic Cad A: 36-42 5 5 Lis A: 19-29 5 5 Diaphus holti VM Mediterranean Bal A: 33-38 5 5 Alb T: 16-18 4 4 Atlantic A: 43 1 1 Cad A: 45-50 5 5 Hygophum benoiti VM Mediterranean Bal T: 11.5-18 10 10 A: 19.5-20 2 2 Alb T: 15-19.4 8 7 Hygophum reinhardtii VM Lis A: 20-39 5 5 Lampanyctus alatus VM Atlantic Cad A: 28-52 4 4 Lis A: 46-70 4 4 Lampanyctus crocodilus VM Mediterranean Bal A: 35.5, 61.5 2 2 Alb A: 61-84 5 5 Lampanyctus pusillus VM Mediterranean Bal T: 10, 18 2 2 A: 10-57.5 4 4 Alb A: 31 1 1 Atlantic Cad A: 25.5-33 5 5 Lis A: 17.5-49 6 6 Lepidophanes gaussi VM Cad A: 18-24 5 5 Lobianchia dofleini VM Mediterranean Bal A: 30-33.5 5 5 Alb A: 25.5-28.5 5 5 Atlantic Cad A: 20.5-25 5 5 Lis A: 25-28 4 4 Myctophum punctatum VM Mediterranean Alb A: 32-49 14 14 Atlantic Lis A: 41.5-60 12 12 Notolychnus valdiviae VM Atlantic Cad A: 18.5-20 5 5 Lis A: 20, 21 2 2 animals-13-00886-t002_Table 2 Table 2 PERMANOVA analysis via the sum of squares Type III, with unrestricted permutations (999) of raw data. Dev: developmental stage; Migrator: migratory pattern; df: degrees of freedom; SS: mean of the sum of squares; MS: mean squares; and perm: permutations. Zone and Dev are nested in fish species. Source Levels df SS MS Pseudo-F-Statistic p (perm) Fish species 28 25 2.56 x 105 10,250 4.6669 0.001 Zone 5 4 51,261 12,815 5.8352 0.001 Zone (fish species) 34 2.07 x 105 6098.9 2.5025 0.001 Dev (fish species) 2 1 8572.6 8572.6 3.9033 0.001 Migrator 3 1 4143.3 4143.3 1.8866 0.02 animals-13-00886-t003_Table 3 Table 3 PERMANOVA pair-wise tests for mesopelagic fish species between zones (only significant results were listed). Bray-Curtis similarity resemblance. Sum of squares Type III. Unrestricted permutation of raw data (999). Sim %: percentage of average similarity between zones; perm: unique permutations; and cum %: cumulative percentage explained by the variable. Prey categories' contribution to average dissimilarity percentages (% diss) considering a 90% cut-off (similarity percentage analysis, SIMPER) is shown on the right side of the table. Groups Sim % t P perm Cum % Prey Categories (% diss) A. hemigymnus Alboran, Cadiz 14.71 1.88 0.03 35 57 Appendicularia (18); Calanoida (13); Clausocalanus + Paracalanus (10); Conchoecia (9) A. hemigymnus Balearic, Alboran 14.79 1.85 0.007 312 58 Appendicularia (23); Calanoida (14); Conchoecia (11); Clausocalanus + Paracalanus (10) C. braueri Lisbon, Galicia 0 1.93 0.046 12 57 Oncaea (22); Calanoida (21); POM (14) C. maderensis Balearic, Alboran 12.55 1.77 0.016 123 53 Appendicularia (21); Copepoda (12); Pleuromamma (11); Conchoecia (9) C. warmingii Cadiz, Lisbon 8.4 2.05 0.01 126 56 Centropages (17); Conchoecia (12); Appendicularia (10); Calanoida (9); Pleuromamma (6) D. holti Balear, Cadiz 19.5 1.83 0.012 126 52 Conchoecia (16); Pleuromamma (11), Oncaea (9); Euphausiacea (8); Chromista (8) D. holti Alboran, Cadiz 35.6 1.88 0.008 126 57 Conchoecia (13); Pleuromamma (12); Oncaea (12); Chromista (10); Appendicularia (10) H. benoiti Balearic, Alboran 23.59 2.05 0.001 987 54 Appendicularia (36); Oncaea (7); Corycaeidae (6); Evadne + Podon (5) L. dofleini Alboran, Cadiz 39.38 2.02 0.005 126 53 Appendicularia (12); Centropages (12); Calanoida (8); Corycaeidae (7); Conchoecia (6); Penilia (6) L. dofleini Balearic, Cadiz 33.78 2.23 0.008 126 50 Oncaea (16); Corycaeidae (14); Euphausiacea (11); Conchoecia (9) L. dofleini Alboran, Lisbon 37.8 1.42 0.024 126 35 Appendicularia (14); Centropages (8); Calanoida (7); Penilia (6) L. dofleini Balear, Lisbon 26.38 1.84 0.006 126 38 Calanoida (9); Euphausicea (8); Centropages (8); Calanus (7); Candacia (7); Larval Euphausiacea (5); Candacia (5); Calanus (5) L. dofleini Cadiz, Lisbon 29.33 2.28 0.01 126 57 Corycaeidae (13); Conchoecia (12); Oncaea (12); Calanoida (7); Centropages (7); Appendicularia (6) L. dofleini Balearic, Lisbon 39.67 1.79 0.006 126 52 Calanoida (9); Euphausiacea (8); Centropages (8); Calanus (7); Candacia (7); Pleuromamma (7); Conchoecia (6) M. punctatum Alboran, Lisbon 17.53 5.85 0.001 999 51 Appendicularia (21); Centropages (11); Euchaeta (10); Calanoida (9) V. tripunctulatus Cadiz, Lisbon 5.04 3.4 0.009 163 61 Pleuromamma (29), Calanoida (12), Conchoecia (11), Centropages (10) animals-13-00886-t004_Table 4 Table 4 PERMANOVA pair-wise tests between developmental stages (groups: transformation and adult including the juvenile stage) and within species. Only significant pair-wise tests are listed. Bray-Curtis similarity resemblance. Sum of squares Type III. Unrestricted permutation of raw data (999). t: t-statistic; df: degrees of freedom; perm: permutations; sim %: percentage of average similarity between and within groups; and prey categories' contribution to average dissimilarity percentages (% diss) considering a 90% cut-off (similarity percentage analysis, SIMPER) is shown on the right side of the table. Fish Species Groups t df p (perm) Sim % Prey Cat (% Diss) A. hemigymnus T, A 1.61 11 0.045 T: 63.9; A: 30.9 T, A: 34.1 Transformation Ostracoda 67.5 Non-Calanoida 30.1 Adult Ostracoda 53.5 Appendicularia 19.1 H. benoiti A T, A 1.75 15 0.01 T: 40.9; A: 38.2 T, A: 30.0 Transformation Oncaea 53.8 Calanoida 22.2 Appendicularia 15.1 Adult Pleuromamma 55.1 Oncaea 45.1 animals-13-00886-t005_Table 5 Table 5 Main contribution of prey categories to the dissimilarity between the diets of migrant and non-migrant mesopelagic fish (similarity percentage analysis, SIMPER). Values in the columns "M" and "NM" are average abundances of the migrant and non-migrant groups, respectively; Av Diss: average dissimilarity; SD: Standard deviation; and Contr: percentage of prey contribution to diet composition. Species M NM Av Diss SD Contr (%) Pleuromamma 0.78 0.33 12.55 0.85 14.75 Non-Calanoida 1.14 0.34 12.39 0.91 14.56 Other Calanoida 1.23 0.32 11.16 0.90 13.11 Eucarida (euphausiids and decapods) 0.36 0.27 8.70 0.61 10.22 Ostracoda 0.44 0.24 7.61 0.66 8.94 Appendicularia 1.16 0.00 7.18 0.50 8.44 Centropages 0.63 0.05 5.24 0.52 6.16 Euchaeta 0.44 0.14 4.70 0.50 5.52 Candacia spp. and Acartia spp. 0.36 0.05 4.24 0.46 4.98 Gelatinous 0.14 0.16 3.48 0.35 4.08 animals-13-00886-t006_Table 6 Table 6 Canonical correspondence analysis for the studied mesopelagic species and the environmental variables SST (sea surface temperature), T450 (temperature at a 450 m depth), and FI (integrated fluorescence). Var (%) is the proportion of variance explained for each variable. P is the significance for each variable. Perms is the number of permutations and inter-set correlations of environmental variables with the first two axes. Species Conditional Effects Inter-Set Correlations Variable Var (%) p Perms F Axis 1 Axis 2 T450 12.6 0.001 999 3.82 -0.6839 -0.1812 SST 11.3 0.003 999 2.96 -0.5571 0.3512 Fl 11.2 0.15 999 1.41 0.5537 0.3547 animals-13-00886-t007_Table 7 Table 7 Trophic guilds defined for the studied species are presented in combination with their migratory behavior and feeding patterns obtained from the estimation of prey carbon weight and prey abundance. The last two columns correspond to the guilds defined in previous studies . M: migrant; PM: partial migrant; and NM: non-migrant. * Predominance of the prey category indicated. ** The species analyzed in the study was the congener L. guentheri, not L. gaussi. Species Trophic-Migratory Guilds Feeding Patterns Based on Hopkins, Sutton, Lancraft (1996) Czujaz et al. (2020) Prey Carbon Weight Count of Prey Items Argyropelecus hemygimnus Zooplanktivore PM Gelatinous, crustaceans Mixed crustacean feeder Not analyzed Not analyzed Argyropelecus sladeni Zooplanktivore PM Mixed crustacean feeder Mixed crustacean feeder Not analyzed Not analyzed Maurolicus muelleri Zooplanktivore M Mixed crustacean feeder Copepod feeder 71% * Small crustaceans * Not analyzed Valenciennellus tripunctulatus Zooplanktivore PM Mixed crustacean feeder Copepod feeder 77% * Small crustaceans * Not analyzed Chauliodus danae Micronektivore M Decapod feeder Mixed crustacean, fish, micronekton, POM Piscivorous Not analyzed Chauliodus sloani Micronektivore M Piscivorous Micronektivore Piscivorous Not analyzed Photostomias guernei Micronektivore PM Other minor categories Euphausiida, Decapoda Decapod feeder Not analyzed Stomias boa [Two guts with prey] Gelatinous Gelatinous Not analyzed Not analyzed Cyclothone braueri Zooplanktivore NM Copepods (Pleuromamma, Euchaeta) * Copepod feeder 60% * Copepod 72% * Not analyzed Cyclothone pallida Gelatinous feeder NM Gelatinous and copepods Gelatinous (Tunicata) Copepod 72% * Not analyzed Cyclothone pseudopallida Zooplanktivore NM Mixed crustacean feeder Copepod feeder Copepod 72% * Not analyzed Cyclothone pygmaea Zooplanktivore NM Small copepod feeder Non-defined Not analyzed Not analyzed Sigmops elongatus Micronektivore PM Euphausiid feeder Euphausiid 61% * Euphausiids 40% * Mixed crustacean NM Vinciguerria attenuata Zooplanktivore M Mixed crustacean feeder Mixed crustacean feeder Small crustaceans Not analyzed Vinciguerria nimbaria Zooplanktivore M Mixed crustacean feeder Mixed crustacean feeder Crustaceans, fish Copepod feeders PM Benthosema glaciale Zooplanktivore M Mixed crustacean feeder Mixed crustacean feeder Not analyzed Not analyzed Benthosema suborbitale Zooplanktivore M Mixed crustacean feeder Micronektivorous Small crustaceans Not analyzed Ceratoscopelus maderensis Generalist M Crustaceans, gelatinous, fish Crustaceans and gelatinous 55% * Not analyzed Copepod feeder M Ceratoscopelus warmingii (Atl) Generalist M Mixed crustacean feeder Crustaceans and gelatinous 20% * Gelatinous 37% * Copepod feeder M Diaphus holti Generalist M Euphausiid feeder Mixed crustacean and gelatinous feeder Not analyzed Not analyzed Hygophum benoiti (Med) Generalist M Mixed crustacean and gelatinous feeder Mixed crustacean and gelatinous feeder Small crustaceans * Not analyzed Hygophum reindhardtii Zooplanktivore M Mixed crustacean feeder Mixed crustacean feeder Mixed crustacean * Not analyzed Lampanyctus alatus Micronektivore M Euphausiid Mixed crustacean feeder Mixed crustacean Not analyzed Lampanyctus crocodilus Micronektivore M Piscivorous Micronektivore Not analyzed Not analyzed Lampanyctus pusillus Micronektivore M Euphausiid feeder 60% Copepod feeder >80% Not analyzed Not analyzed Lobianchia dofleini Generalist M Mixed crustacean feeder (copepods, euphausiids) Mixed crustacean and gelatinous feeder Not analyzed Not analyzed Lepidophanes gaussi (Atl) Copepod feeder M Copepod feeder (Pleuromamma, Candacia) Mixed crustacean feeder Mixed crustacean feeder Copepod feeder M ** Myctophum punctatum Zooplanktivore M Mixed crustacean, gelatinous feeder Gelatinous and copepod feeder Not analyzed Not analyzed Notolychnus valdiviae (Atl) Copepod feeder M Copepod feeder Copepod feeder Small crustaceans * Not analyzed Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000213 | A total of 1039 non-dairy breed (Romney) ewes were enrolled in two studies to assess the changes in udder half defect status (hard, lump, or normal) over time and to predict the risk of future udder half defect occurrence. In the first study (study A), udder halves of 991 ewes were assessed utilizing a standardized udder palpation method and scored four times a year, for two successive years (pre-mating, pre-lambing, docking, and weaning). The second study (study B) assessed the udder halves at pre-mating, and at six weekly intervals in the first six weeks of lactation in 46 ewes that had defective and normal udder halves. Udder half defect change over time was visualized via lasagna plots, and multinomial logistic regression was used to predict the risk or probability of udder half defect occurrence. In the first study, the highest occurrence of udder halves categorised as hard was observed at either pre-mating or docking. Udder halves categorised as lump had their highest occurrence at either docking or weaning. Udder halves detected with a defect (hard or lump) at pre-mating were more likely (RRR: 6.8 to 1444) to be defective (hard or lump) at future examinations (pre-lambing, docking, or weaning) within the same year or pre-mating the following year, compared to udder halves categorised as normal. In the second study, the change of udder half defect type over the first six weeks of lactation was variable. However, it was observed that the udder half defects, particularly udder halves categorised as hard, decreased during lactation. Failure to express milk in udder halves in early lactation was associated with a higher occurrence and persistency of udder half defects. In conclusion, the occurrence of diffuse hardness or lumps in an udder half changed over time, and the risk of future occurrence of a defect was higher in udder halves previously categorised as either hard or lump. Hence, it is recommended that farmers identify and cull ewes with udder halves categorised as hard and lump. change over time culling diffusely hard udder non-dairy ewe palpable udder defect relative risk and udder lump Beef and Lamb New Zealand16MU07 This project was funded by Beef and Lamb New Zealand (16MU07). pmc1. Introduction Poor udder health can have serious impacts on the welfare of suckling lambs and reduce the longevity of ewes within the flock . In non-dairy ewes, defective udders are associated with lower lamb survival and decreased lamb live weight gain during the pre-weaning period . Udder defects are abnormalities of the udder, the causes of which can range from non-mechanical injury to infectious agents . Several terminologies have been used to describe defective udders such as "impaired udders", "imperfect udder", "unsound udder", "faulty udder", "udder with abnormality" and "defective udder" . Udder defects include abnormal secretion, inflammation, nodules or mammary masses, diffuse hardness, cysts, fibrosis, teat occlusion, teat canal cord formation, lumps, and ruptured abscesses on the udder . Clinically, ewe udder defects can be detected by physical palpation and, on occasion, visually . Standardized udder assessment is a useful tool to identify defective udders of ewes to provide timely selective treatment or make culling decisions . Udder defect assessment in non-dairy ewes usually takes place either at weaning or prior to mating when farmers are selecting ewes for the next breeding season . More than 75% of New Zealand farmers reportedly assess their ewes' udders at least once a year, which is assumed for the purpose of making culling decisions . Ridler, et al. recommended that ewe udders are examined at least four to six weeks post-weaning as issues not identified at weaning can be more easily identified. Palpable udder defects such as hardness within the udder and various-sized lumps have been reported during pregnancy, lactation, and/or the dry period in ewes . The hard udder has been described as a diffuse hard consistency of the udder upon palpation . Udder lumps (abscesses) have been described by several authors and have been reported to show phenotypic diversity in size, consistency, and location upon clinical and post-mortem examination of udders . Repeated udder examinations of the same flock of ewes within a season in New Zealand and across two seasons in the United Kingdom both showed phenotypic diversity and a varying percentage of udder defects on consecutive examinations. Ridler, et al. also reported changes in udder defects across two visits, where the first visit was on the day of weaning followed by the second visit four to six weeks later. In that study, ewes with hard udders at the first visit changed to normal or lump or remained hard while there was a small number of normal udder halves at the first visit that were subsequently found to have defects at the second visit. Bruce, et al. reported that "hard udder" typically occurred shortly after lambing and then appeared to regress, with involution of the gland occurring within 3-4 weeks of initial lesion detection. In addition, Peterson, et al. reported hard udders identified by palpation three weeks post-weaning had changed to normal palpation scores several months past weaning. Smith, et al. hypothesized that the phenotypic diversity of palpable udder lumps (abscesses) could be due to the maturation cycle of the abscesses. Combined these studies imply that udder defects can change over time. Further, Grant, et al. reported that ewes that were identified with palpable udder defects were three to five times more likely to have udder defects identified in the future. Understanding the dynamic nature of palpable udder defects over time could provide important information regarding when higher rates occur and the best possible time for an intervention. Additionally, such studies could provide reliable information regarding the appropriate culling of affected ewes, by predicting the likelihood of recurrence within the same or the following year/season. Therefore, the objectives of these studies were: to assess the changes in udder half defect status over time, both over two full years and during a single lactation; and to predict the risk of future udder half defect occurrence. 2. Materials and Methods This manuscript utilized data from two studies. Study A was undertaken under commercial conditions and utilised longitudinal data gathered over a two-year period from 2017 to 2018. Study B used data from 48 ewes with a history of either udder defects or normal udders. In study B, all ewes were presented for machine milking once followed by hand stripping according to Peterson, et al. in the first six weeks of lactation in 2019. In both studies, lambs were with their dams until weaning. 2.1. Study A: Ewe Selection and Management The study comprised the entire cohort of 2013 (n = 590) and 2014-born (n = 391) replacement ewes at Massey University Riverside farm (n = 981 on 17 February 2017, at pre-mating, Wairarapa, New Zealand). All ewes had lambed at least once prior to joining the study. Ewes were ear tagged with visual (VID; Allflex, Palmerston North, New Zealand) and electronic (EID; Allflex, Palmerston North, New Zealand) identification tags. In autumn each year (March), rams were introduced to the ewes for breeding at a ratio of approximately 1:150 for two oestrus cycles (34 days). Transabdominal ultrasonography was undertaken by a commercial practitioner during mid-pregnancy to diagnose pregnancy status and determine the number of foetuses. Throughout the study period, ewes were managed under commercial conditions with individual feeding decisions at the flock level, being at the discretion of the farm manager. The predominant pastures were ryegrass (Lolium perenne) and white clover (Trifolium repens). At pre-lambing (set-stocking), approximately 10 days before the expected start of lambing, the ewes were divided into three groups accounting for expected litter size (singleton-, triplet-bearing). Pasture measurements were not taken, but the ewes were allocated into different paddocks for lambing at a rate of approximately 7 to 12 ewes per hectare, based on the expected litter size. Lambing took place in spring and during lambing ewes were monitored twice daily to match lambs to their dams. Lambs were given an electronic identification tag and relevant information on newborn lambs was recorded: dam ID, date of birth, sex, birth rank, and birth weight. Ewes were culled based on routine farm practices such as feet and teeth; however, ewes were not culled based on udder health. Non-pregnant ewes were also culled each year. In addition, throughout the study, ewes that required euthanasia on welfare grounds were euthanised. 2.2. Study B: Ewe Selection and Management In December 2018, 80 ewes aged 5-6 years were obtained from Massey University's Riverside farm, Wairarapa, New Zealand. These ewes were selected based on udder traits evaluated during Study A. Sixty of these ewes had one or more udder half defects (hard and/or lump) or a history of udder half defects over the previous two years whereas 20 ewes had never been recorded as having an udder half defect. After selection, these ewes were moved to Massey University's Keeble farm, which is located 5 km southeast of Palmerston North, New Zealand. Ewe selection, reproductive management, pregnancy diagnosis, culling and lambing, and management were described in our previous publication . 2.3. Body Condition Scoring (BCS) and Live Weight In both studies, BCS was assessed by an experienced assessor by palpating the lumbar region and feeling the vertical (spine) and horizontal processes along the loin area. The body condition scoring system was a 5-point system (1-5, where: 1 = thin and 5 = obese) assessed at 0.5 intervals . Ewes were weighed by using static digital weighing scales (model XR5000, Tru-Test Group, Auckland, New Zealand) to the nearest 0.2 kg at each body condition scoring event. Body condition scoring and live weight measurement of each ewe were also assessed on udder scoring days. 2.4. Udder Scoring Ewe udders were assessed by trained and experienced assessors with ewes restrained by experienced sheep handlers in a sitting position. Udder halves were scored from 1-7 using the system described by Griffiths, et al. ; however, the scores were then collapsed down to three categories: normal (scores 1 and 2); hard (score 7); and lump (scores 3-6). In Study A, udders were assessed four times per year for two consecutive years (2017-2018) at pre-mating (February), pre-lambing (September), docking (3-8 weeks after lambing, November), and weaning (December). These time points were selected as they represent key management events when farmers traditionally interact with individual ewes. Four trained operators undertook the udder palpations in Study A. Previous studies on udder defects in ewes reported a higher occurrence in early lactation compared to weaning and post-weaning periods . According to the same authors, a change in udder defect status was observed shortly after lambing. Therefore, in Study B, udders were assessed at pre-mating and then once weekly in the first six weeks of lactation beginning from 4-10 days after parturition. In Study B a single operator undertook all udder palpations to avoid potential inter-operator variation. 2.5. Data Analysis In Study A, all 981 ewes (1962 udder halves) in 2017, 769 ewes (1538 udder halves) in 2018, and 704 ewes (1408 udder halves) in both years were included in the analysis. In Study B, 48 ewes (92 udder halves) were assessed weekly in the first six weeks of lactation. However, in both studies, only udder halves with complete data for all scoring events within a plot were considered for the lasagna plots. 2.5.1. Descriptive Analysis--Lasagna Plots To analyse the dynamic nature of udder defects the lasagna plot method was identified as the most suitable option. Lasagna plots allow visualization of the changes in the defect category (hard, lump, or normal) of udder halves over time (for the different udder scoring events). Within the plots, each bar shows a different udder scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of the plot designates the percentage of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. A change in the colour of each udder-half category at a different time event represents a change in the udder-half category. The lasagna plots were created using SAS Statistical software Version 9.4 (SAS Institute Inc., Cary, NC, USA) utilizing the methodology of Jones, et al. . Three lasagna plots were created using udder half data from Study A: (i) four udder examination events in 2017 comprising 1860 udder halves (930 ewes), (ii) four udder examination events in 2018 comprising 1428 udder halves (714 ewes), and (iii) all eight udder examination events across 2017 and 2018 comprising 1408 udder halves (704 ewes). Four lasagna plots were created for Study B, (i) pre-mating and six udder examination events during their single lactation which comprised data from udder halves from which milk was expressed during the once-weekly milking events (43 udder halves), (ii) pre-mating and six udder examination events during lactation which comprised data from udder halves from which milk was not expressed (37 udder halves), (iii) pre-mating and six udder examination events during their single lactation which comprised data from udder halves from which had a previous history of udder half defect (58 udder halves), (iv) pre-mating and six udder examination events during lactation which comprised data from udder halves from which milk had no previous history (i.e., normal) of udder half defect (22 udder halves). Udder halves that did not express milk were defined as those udder halves from which no milk was expressed from at least four of the six weekly milking events and expressed less than 100g/day in the rest, otherwise, an udder half was considered as expressed milk. 2.5.2. Multinomial Logistic Regression Study A. A series of multinomial logistic regression models were developed utilising data from 1962 udder halves in 2017, and 1562 udder halves in 2018 to predict the relative risk ratio of udder half defect status (hard, lump, or normal) at pre-lambing, docking, and weaning for the 2017 year and the 2018 year, based on the udder half defect status at pre-mating of each respective year being analysed. Two models were fitted from data of the 1426 udder halves that were measured across both years to predict the relative risk ratio of the udder half defect status at pre-mating in 2018 based on pre-mating and weaning data in 2017. Birth rank (singleton or twin ), rearing rank (no lambs reared , reared a single lamb or reared twin lambs ), udder half (right/left), age of ewes (2013 or 2014 year of birth) and ewe BCS and bodyweight at premating were included as covariates. For all the models developed, the probability of each udder half defect category at each udder scoring event was extracted. Study B. Several multinomial logistic regression models were fitted to assess weekly transitional probability using data from 48 ewes during the first six weeks of lactation, conditionally on the preceding udder palpation event (e.g., Day 7 udder defect status was used to predict Day 14 udder defect status, Day 14 for Day 21, and so forth for the six examinations during lactation). Birth rank (singleton or twin ), rearing rank (no lambs reared , reared a single lamb , or reared twin lambs ), udder half (right/left) and udder half milk expression status (yes/no) were included as covariates. A separate analysis, using the same model structure, was undertaken to predict the probability of each udder half defect category in the six examination events during lactation (Day 7 to Day 42) based on the pre-mating udder half defect status of the ewes at mating in 2019. All analyses were performed using a multinomial logistic regression approach with a 'multinomial' function from the 'net' package in R statistical software version 3.6.3 . Interactions between variables were tested. The model development process was based on the backward selection of the independent variables mentioned. The goodness of fit of the models was tested for significance by the likelihood ratio test (also called model chi-square). Variance inflation factor was applied to assess the multicollinearity while the goodness of fit was assessed by McFadden's pseudoR2. 3. Results 3.1. Study A: Lasagna Plots of Udder Half Defects in 2017 and 2018 Overall, at least 94.8% of udder halves were normal at each individual udder examination event, although new udder half defects were detected at each additional examination event from those udder halves previously categorised as normal . Amongst udder halves that had defects (hard or lump) or those that developed defects, the lasagna plots demonstrate that defects either remained the same over time, changed to normal, or changed to another defective category, i.e., all possible changes occurred although only a relatively small proportion of ewes had or developed defects. Only six (0.3%) udder halves in 2017 and 16 (1.0%) udder halves in 2018 stayed defective (remained in the same category or changed to another defective category) at all udder examination events within each year. However, none of the udder halves remained defective in all eight udder examinations throughout both years. In both years, the percentage of udder halves categorised as hard was higher at the pre-mating examination compared with pre-lambing (late-pregnancy). The percentage increased again at docking before slightly decreasing at weaning . Udder halves, categorised as lumps, were more commonly identified during lactation (i.e., identified at docking and weaning) compared to during the non-lactation periods . A comparison of the same examination periods across years showed that the percentage of udder halves that were defective was higher at pre-mating (0.4%) and docking (0.9%) in 2018 compared to 2017 . From eight udder examination events over the two-year period, the highest percentage of udder half defects was observed at docking 2018. Additional plots are included in Figure A1, Figure A2 and Figure A3, corresponding to Figure 1A-C, respectively, which show changes in the udder half defect category over time for those udder halves with a defect on at least one occasion. 3.2. Study A: Relative Risk Ratios of Udder Half Defects at Pre-Lambing, Docking, and Weaning in 2017 and 2018 Based on Pre-Mating Status If an udder half was categorised as hard at pre-mating, it was more likely to be categorised as hard at pre-lambing, docking, and weaning in both 2017 (Table 1) and 2018 (Table 2) compared to an udder half that was categorised as normal at pre-mating. The relative risk ratios (RRR) ranged from 14 to 1465 (p < 0.05) when other variables in the model were held constant. If an udder half was hard at pre-mating (within each respective year), the relative risk of it being categorised as a lump at the following pre-lambing in 2017 and pre-lambing, docking, and weaning in 2018 was higher (RRR range 14 to 1465 times) compared to an udder half that was categorised as normal at pre-mating while keeping all other variables constant. Udder halves categorised as a lump at pre-mating (within each year) were more likely (p < 0.05) to be categorised as hard at pre-lambing, docking, and at weaning in 2017 and at pre-lambing and docking in 2018, compared with udder halves that had been categorised as normal at pre-mating, when other variables were held constant in the model (RRR range 6 to 67, Table 1 and Table 2). In addition, udder halves categorised as lumps at pre-mating were more likely to be categorised as lumps at pre-lambing, docking, and weaning in both 2017 and 2018, compared to udder halves that had been categorised as normal at pre-mating, when other variables held constant in the model (RRR range from 6 to 333, Table 1 and Table 2). Among the covariates considered for models examining udder half defects across key management times, rearing rank was the only covariate that significantly (p < 0.05) influenced udder half defects and only at docking in both years. A rearing rank of zero (no lambs suckling) was associated with a higher relative risk of an udder half being categorised as a lump at docking in 2017 and both hard or lump at docking in 2018, compared with the reference rank of one lamb suckling. In both 2017 and 2018, ewes that reared twins were less likely to have udder halves categorised as hard (OR = 0.2, p < 0.05) compared to the reference of ewes that reared single lambs (Table 1 and Table 2). 3.3. Study A: Predicted Probabilities of Udder Half Defects at Pre-Lambing, Docking, and Weaning in 2017 and 2018 Based on Pre-Mating Status For udder halves categorised as normal at pre-mating, the vast majority remained normal at pre-lambing, docking, and weaning across both years (predicted probability (Pp) of 0.96-0.99, Table 3). In both years, the probability was highest at pre-lambing followed by docking and then weaning. For udder halves that were categorised as normal at pre-mating, the Pp that they would subsequently change to hard or lump was very low in both years (i.e., less than 0.036, Table 3). For those udder halves that were categorised as hard at pre-mating, the Pp of remaining hard or changing to hard was variable between years and time points; however, it was higher in 2018 than in 2017. In contrast, the Pp of these udder halves being categorised as normal ranged from 0.73 to 0.83 in 2017 but was much lower in 2018 (Table 3). For those udder halves that were categorised as lumps at pre-mating, the Pp of changing to normal was lowest at docking in both 2017 and 2018 (Table 3). The Pp of udder halves categorised as lump changing to hard was higher in 2017 compared to 2018, but the highest probability was observed at docking in both years. The Pp of udder halves categorised as lump remaining as lump ranged from 0.069 to 0.296. 3.4. Study A: Relative Risk Ratio of Udder Half Defects at Pre-Mating 2018 Based on Weaning and Pre-Mating 2017 If an udder half was categorised as defective (hard or lump) at pre-mating in 2017, the RRR of it still being categorised as defective (hard or lump) at pre-mating in 2018 was higher (RRR range 6.6 to 15.4, p < 0.05) compared with udder halves categorised as normal at pre-mating in 2017 (Table 4). Keeping all other covariates constant, for udder halves categorised as hard at weaning in 2017, the RRR of being categorised as hard or as a lump at pre-mating in 2018 was 141 and 53 times higher (p < 0.05) respectively, compared with an udder half that was categorised as normal at weaning in 2017. If an udder half was categorised as a lump at weaning in 2017, the RRR of it being categorised as hard or lump at pre-mating 2018 was 6 and 16 times higher (p < 0.05) respectively, compared with an udder half that was categorised as normal at weaning in 2017 (Table 4). 3.5. Study B: Lasagna Plots of Udder Half Defects at Pre-Mating and Day 7 to 42 of Lactation in Udder Halves with or without a Previous History of Udder Defect From a total of 22 udder halves that had no history of udder half defects in the previous two years (2017 to 2018), only 9 (41%) udder halves were found to be normal throughout all examinations. In contrast, in udder halves that had a history of udder half defects, 19% exhibited no udder half defects throughout all udder examinations. Udder half defects appeared to be highly variable with multiple changes over time, at pre-mating and during the first six weeks of lactation , particularly for those udder halves that had a previous history of defects . The percentage of udder half defects, and their persistence, appeared to be higher in udder halves that had a previous history of defects compared with those that had not . From a total of 22 udder halves that had no defect history, only one udder half (4.5%) was categorised as a lump on Day 7 of lactation while the rest were categorised as normal . The number of udder halves that had no defect history and were categorised as hard was highest on Day 14, and this was the only day that any of these 22 udder halves were categorised as hard. All udder halves categorised as hard on Day 14 had changed to normal by Day 21 and this persisted until Day 42; however, two (9%) udder halves changed to lump on Day 35. In udder halves with no defect history, only one new defect was observed on Day 35 and no new defect was observed in the following weeks. From a total of 62 udder halves that had a previous history of defect, the percentage that was categorised as normal over six weeks of lactation appeared to be lower compared with those that had no defect history . Fifty percent of udder halves that had a previous defect history were categorised as hard on Day 7, and over subsequent weeks, these udder halves changed category, such that no udder half remained consistently hard at all examinations. As the days in lactation increased, the percentage of udder halves categorised as hard decreased substantially. The percentage of udder halves that had a previous history of defects, and were subsequently categorised as lump, were higher on Day 14 compared with Day 7. At subsequent examinations, the percentage categorised as lump fluctuated over the weeks. 3.6. Study B: Lasagna Plots of Udder Half Defects at Pre-Mating and Day 7 to 42 of Lactation in Udder Halves That Did and Did Not Express Milk Milk expression status (yes/no) had a significant (p < 0.05) effect on the udder half defect. Compared to normal udder halves, those udder halves that did not express milk had higher RRR of being hard (OR = 7.9-35.4) on Days 14 and 21 and higher RRR of being lump (OR = 6-26, p < 0.05) on all six occasions during lactation compared to the normal udder halves. Except for one udder half, all udder halves that had no history of defect expressed milk whereas only 35% of udder halves that had a previous history of udder half defect expressed milk. Plots were made for udder halves that did express milk and those that did not . 3.7. Study B: Weekly Transitional Probability of Udder Half Defects from Day 7 to 42 of Lactation In the first six weeks post-lambing, weekly udder half defect category transitions (from Day 7 to 14, from Day 14 to 21, and so on) identified that all possible transitions across categories occurred . The probability of weekly transition of udder halves categorised as normal remaining normal increased as days in lactation advanced from Day 7 to 42. In contrast, the transitional probability of a normal udder half changing to an udder half categorised as either hard or lump declined . The weekly transitional probability of udder halves categorised as hard changing to normal was high (>0.8) during the first three weeks (Day 7 to 21) of lactation and remained steady until it declined from Day 28 . The weekly transitional probability of an udder half categorised as hard that remained hard, increased as lactation advanced from Day 7 to 42, whereas the probability of transition from hard to lump slightly decreased. The weekly transitional probability of udder halves categorised as lump transitioning to normal declined from day 7 to Day 35 but then started to rise at Day 42 . In contrast, the weekly transitional probability of udder halves categorised as lump remaining as lump increased from Day 7 to day 35 and then declined at Day 42. The probability of an udder half categorised as a lump transitioning to hard was variable among the udder scoring days, but it was generally low (Pp < 0.09). 3.8. Study B: Predicted Probability (Pp) of Udder Half Defect from Day 7 to 42 in Lactation Based on Pre-Mating Udder Half Defect The predicted probability (Pp) of udder half defect in the first six weeks of lactation (Day 7 to Day 42) based on pre-mating udder half defect status is summarized in Table 5. For udder halves that were normal at pre-mating, the Pp of an udder half remaining normal was high (Pp range 0.674-0.986) at all six events. For those that were categorised as normal at pre-mating, the Pp of being categorised as hard was highest on Day 7, before it dropped close to zero for the next four weeks and then rose again on Day 42. Whereas the Pp of an udder half being categorised as a lump was low on Day 7, peaked on Day 14, and then declined. Only three udder halves were categorised as hard at pre-mating but the Pp of them being normal on Day 7 was very high, then declined while the Pp of being categorised as hard declined over lactation. For those that were categorised as hard at pre-mating, the Pp of being categorised as a lump was very low on Day 7 and was then higher in the subsequent weeks. For udder halves categorised as lumps at pre-mating, the Pp of being normal increased with days in lactation, until Day 28, before declining in the following two weeks. For those udder halves that were categorised as lumps at pre-mating, the Pp of being categorised as hard was very high on Day 7 and then decreased from Day 14 while the Pp of being categorised as a lump was variable over time but was highest on Day 42. All three udder halves categorised as hard at pre-mating expressed no milk during the first 42 days in lactation, but due to low numbers, this was not significant (p < 0.05). Udder halves categorised as lumps at pre-mating were four times more likely (p < 0.05) not to express milk, compared to udder halves categorised as normal at pre-mating. 4. Discussion The objectives of the study were to assess the changes in udder half defects over time and determine the risk of future occurrence of udder half defects in non-dairy ewes. For this purpose, across two studies, a standardized udder assessment method was implemented at pre-mating, pre-lambing, docking, and weaning for two years or weekly in the first six weeks of lactation. The assessment was undertaken at the udder half level as each mammary gland is anatomically and/or physiologically independent. Lasagna plots were used to present the data as it enabled easy visualisation of changes in the udder half category over time. In Study A, which evaluated udder halves at eight time points over two years, most udder halves were categorised as normal, while only a low percentage of udder halves were categorised as hard or lump, matching previous studies when time-specific evaluations have been undertaken. However, the relatively large number of ewes included in the study still meant that meaningful analysis could be undertaken. Most udder halves categorised as having defects (either hard or lump) changed in category over time, while a small percentage of new defective udder halves (i.e., from udder halves previously categorised as normal) were observed at each time point. This approach demonstrated the dynamic nature of udder half defects and helps explain why repeated examinations of the same flock have previously resulted in different percentages of udder defects . The proportion of udder halves categorised as hard was higher at docking (Study A) or the first couple of weeks in lactation (Study B). Similarly, a higher occurrence of hard udder or other udder defects shortly after lambing has been reported by others and could be due to the peri-parturient relaxation of immunity which makes the udder susceptible to infection . The occurrence of udder halves categorised as hard was also higher at pre-mating. The post-lactation involution period has been associated with mammary gland susceptibility, increased risk of infection, or advancement of subclinical infection to clinical because of compromised mammary defences in this period . It can also be related to the occurrence of post-weaning chronic mastitis . Udder halves categorised as lumps were more commonly identified during lactation (i.e., identified at docking and weaning) compared to during the non-lactating period (i.e., identified at pre-mating and pre-lambing). This agrees with Grant, et al. who reported higher palpable udder defect occurrence in lactation compared to pregnancy. Lumps or intramammary abscesses usually occur following an intramammary infection (IMI) , which, in the case of this study, is likely to be first observed after early post-lambing infection or complication. Higher occurrence of lumps at weaning might be associated with physiological changes in early cessation of lactation and initiation of involution that compromise mammary gland immunity, particularly in those that did not express milk . Utilizing an objective udder assessment method and making rational culling decisions is important to improve the health and welfare of pre-weaned lambs . This can optimally be achieved by predicting the occurrence of udder defects in the next breeding season based on udder examination prior to mating at the time of ewes' selection (for retention or culling). Pre-mating udder examination has been suggested to be an appropriate time to identify ewes that are likely to be unsuitable for retaining in the breeding flock as ewes with udder halves categorised as hard or lump at pre-mating were associated with lower lamb survival and body weight gain in pre-weaned lambs . In this study, an udder half categorised as hard or lump at pre-mating was more likely to remain as hard or change to lump compared with the normal udder halves in at least one of the key management times in the same year (pre-lambing, docking, and weaning). The findings of this study support the practice of farmers culling ewes identified with defects at weaning or premating . A comparison of the same examination periods across years (Study A) showed that the percentage of udder halves that were defective at pre-mating and docking was higher in 2018 than in 2017. Similarly, palpable udder defects during a previous lactation were associated with an increased risk of udder defects in the current lactation in ewes in the United Kingdom . This is likely a function of time; in this study, ewes with udder defects were not culled, therefore, as more ewes developed udder defects over time the percentage of identified defects would have increased. Further, given the high reappearance rates in Study B and the impact on lamb performance, the results of these studies suggest that ewes with hardness or lump/s within one or both udder halves should be culled regardless of the apparent severity of the defect at the time of examination. In ewes with a previous history of udder half defects (Study B), the presence of udder half defects during the first six weeks of lactation was high and highly variable with numerous defect-type changes. The high occurrence in early lactation could be due to high production stress stimulating compromises in mammary defence systems following lambing . During lactation, the occurrence of udder half defect was higher and more consistent over time in those udder halves that did not express milk in comparison with udder halves from which milk was expressed. Smith, et al. reported that palpable udder defects are associated with abnormal secretions or abscesses in the mammary gland while abscesses take a couple of weeks to mature before spontaneously resolving or bursting . This could explain the high occurrence and persistency of defects over time in those udder halves that did not express milk. Others have reported that udder defects can also induce early involution which may further compromise mammary immunity . On the other hand, mammary emptying in those udder halves that do express milk might be helpful to prevent further health complications . The overall frequency of defective udder halves decreased as the days in lactation increased. Udder halves categorised as hard declined substantially, as an udder half categorised as hard was more likely (80%) to change to normal in the first five weeks of lactation. This result agrees with previous reports of a higher occurrence of "hard udder" shortly after lambing but within two to three weeks the udder appeared normal . Although the number of udder halves categorised as hard decreased significantly over time, if an udder half was still hard on Day 35, the probability of remaining hard was very high (>90%). This could be due to considerably decreased milk production or the initiation of early involution which compromises the mammary immunity as in the case of normal involution during drying off . An udder half categorised as a lump was more likely to change to normal in the first five weeks of lactation, but the probability declined as the days in lactation increased. The probability of an udder half categorised as a lump to remain lump increased for the first four weeks in lactation and started to decrease on Day 35. This might be associated with the development and maturation of an abscess that bursts a couple of weeks later . In the first six weeks of lactation, the probability of new defect development (normal to hard or lump) was very low, and it decreased as the days in lactation increased. Udder palpation scoring is an easy and practical method of udder assessment in ewes. Nevertheless, the technique could be relatively subjective depending on the physiological state of the udder (i.e., lactating or involuted) and the operators' skill. To minimize potential variation or misclassifications, in Study A, the same four trained operators undertook the udder palpations while in Study B the same person undertook all udder palpations. However, the outcomes may have been missed, misclassified, or over-interpreted, and therefore, results should be interpreted with this in mind. In conclusion, udder half defect status changed over key management times such as pre-mating, pre-lambing, docking, and weaning in a year, and also weekly in early lactation. The highest occurrence of udder halves categorised as hard was observed during the non-lactating period and early lactation (pre-mating or docking) whereas in udder halves categorised as lump, the highest occurrence was during lactation (docking and weaning). Udder half defects categorised as hard or lump at pre-mating were more likely to be defective (hard or lump) at future examinations at key management times in the year or pre-mating of the following year. Udder halves that did not express milk in early lactation had a higher occurrence and persistency of udder half defects compared with those that did express milk. Therefore, it is recommended that farmers identify and cull ewes with udder halves categorised as hard and lump. However, further consideration should be given to the dynamic pattern of udder half defect changes over time and their persistency, the status of the contralateral udder half, and the ultimate effect on whole udder milk production. Acknowledgments We want to thank Geoff Purchas, Dean Burnham, and Catriona Jenkinson for their technical support. Author Contributions Conceptualization, M.M.Z., A.L.R., K.J.F. and P.R.K.; data collection, M.M.Z., A.L.R. and K.J.F.; data analysis, M.M.Z.; data curation, M.M.Z., P.R.K. and K.J.F.; supervision, A.L.R., P.R.K., S.J.P. and D.A.; writing--review and editing, K.J.F., A.L.R., P.R.K., D.A. and S.J.P. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement All procedures involving the use of live animals were undertaken in accordance with animal welfare standards and approved by the Massey University Animal Ethics Committee (Application numbers: MUAEC 15/105 and 18/99). Data Availability Statement The data utilised by this study are available on request from the corresponding author. Conflicts of Interest The authors declare no conflict of interest. Appendix A Figure A1 Lasagna plot of palpable udder half defects (hard, lump and normal) from non-dairy Romney ewes identified during udder examination events occurring at key management times (pre-mating, pre-lambing, docking, and weaning; Study A). Lasagna plot of 231 udder halves in year 2017, excluding udder halves observed with no udder defect on all occasions. Note: Within each plot, each bar shows a different udder half scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of each plot designates the percentage (%) of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Figure A2 Lasagna plot of palpable udder half defects (hard, lump, and normal) from non-dairy Romney ewes identified during udder examination events occurring at key management times (pre-mating, pre-lambing, docking, and weaning; Study A). Lasagna plot of 109 udder halves in the year 2018, excluding udder halves observed with no udder defect on all occasions. Note: Within each plot, each bar shows a different udder half scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of each plot designates the percentage (%) of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Figure A3 Lasagna plot of palpable udder half defects (hard, lump, and normal) from non-dairy Romney ewes identified during udder examination events occurring at key management times (pre-mating, pre-lambing, docking, and weaning; Study A). Lasagna plot of 214 udder halves in the years 2017 and 2018, excluding udder halves observed with no udder defect on all occasions. Note: Within each plot, each bar shows a different udder half scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of each plot designates the percentage (%) of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Appendix B Figure A4 Lasagna plot of palpable udder half defects (hard, lump, and normal) in the first six weeks of lactation in non-dairy Romney ewes (Study B). Udder examination was undertaken at weekly intervals from 43 udder halves that did express milk. Note: Within each plot, each bar shows a different udder scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of the plot designates the percentage of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Note that an udder half that did not express milk refers to an udder half that did not express milk at all on at least four occasions and expressed less than 100 g/day on the other two occasions. Figure A5 Lasagna plot of palpable udder half defects (hard, lump, and normal) in the first six weeks of lactation in non-dairy Romney ewes (Study B). Udder examination was undertaken at weekly intervals from 37 udder halves that did not express milk. Note: Within each plot, each bar shows a different udder scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of the plot designates the percentage of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Note that an udder half that did not express milk refers to an udder half that did not express milk at all on at least four occasions and expressed less than 100 g/day on the other two occasions. Figure 1 Lasagna plot of palpable udder half defects (hard, lump, and normal) from non-dairy Romney ewes identified during udder examination events occurring at key management times (pre-mating, pre-lambing, docking, and weaning; Study A). (A) Lasagna plot of 1860 udder halves (930 ewes) in the year 2017; (B) 1428 udder halves (714 ewes) in the year 2018; (C) 1408 udder halves (704 ewes) from 2017 and 2018 combined. Note: Within each plot, each bar shows a different udder half scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of each plot designates the percentage (%) of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Figure 2 Lasagna plot of palpable udder half defects (hard, lump, and normal) in the first six weeks of lactation in non-dairy Romney ewes (Study B). Udder examination was undertaken at weekly intervals from 22 udder halves that had no history of defects in the previous two years (2017 and 2018); (A) and from 58 udder halves that had a history of defects (B). Note: Within each plot, each bar shows a different udder scoring event (i.e., time) while the different colours within each bar represent the defect categories. The data in the table at the top of the plot designates the percentage of each udder half defect category at each event, which corresponds to the percentage of each colour at each event. Change in defect category over time of each udder half can be tracked by following longitudinal transitions across the udder scoring events of stacked bars. Six ewes that missed the udder examination on Day 42 were excluded from the plot. Figure 3 Line graph of the transitional probability of udder half defects in the first six weeks of lactation from 92 udder halves (from 46 non-dairy Romney ewes) in 2019 (Study B). (A) Transitional probability of udder half defect from preceding normal state; (B) Transitional probability of udder half defect from preceding hard state; (C) Transitional probability of udder half defect from preceding lump state. Probabilities were predicted conditionally on the preceding udder palpation event (e.g., Day 7 udder defect status was used to predict Day 14 udder defect status, Day 14 for Day 21, and so forth for the six examinations during lactation). animals-13-00784-t001_Table 1 Table 1 Relative risk ratio (RRR +- standard error) of udder half defect category (normal, hard, or lump) at pre-lambing, docking, and weaning based on pre-mating udder half defect category from 1962 udder halves (from 981 non-dairy Romney ewes) in 2017 (Study A). Predictor Variables Category Udder Half Defect (2017) Hard Lump pre-lambing Pre-mating udder half defect Normal (Reference) - - Hard 52.9 (0.9) 13.8 (0.4) Lump 26.5 (1.2) 6.9 (0.6) Constant 0.002 (0.6) 0.002 (0.1) docking Pre-mating udder half defect Normal (Reference) - - Hard 14.1 (0.6) 1.01 NS (1.0) Lump 42.0 (0.55) 5.5 (0.65) Rearing rank Single (Reference) - - No lambs 1.8 NS (0.6) 3.6 (0.5) Twins 0.2 (0.65) 1.7 NS (0.3) Triplets 3.0 NS (0.8) 1.9 NS (0.8) Constant 0.01 (0.3) 0.02 (0.3) weaning Pre-mating udder half defect Normal (Reference) - - Hard 43.3 (0.6) 3.3 NS (0.6) Lump 26.0 (0.7) 6.7 (0.5) Constant 0.01 (0.3) 0.04 (0.1) Note: All relative risk ratios (RRR) were significant (p < 0.05), except those designated as NS (not significant, p > 0.05). animals-13-00784-t002_Table 2 Table 2 Relative risk ratio (RRR +- standard error) of udder half defect category (normal, hard, or lump) at pre-lambing, docking, and weaning based on pre-mating udder half defect category from 1538 udder halves (from 769 non-dairy Romney ewes) in 2018 (Study A). Predictor Variables Category Udder Half Defect (2018) Hard Lump pre-lambing Pre-mating udder half defect Normal (Reference) - - Hard 1465 (1.1) 1462 (1.0) Lump 66.6 (1.4) 333 (1.1) Constant 0.001 (1.00) 0.001 (0.9) docking Pre-mating udder half defect Normal (Reference) - - Hard 292.5 (0.7) 169.3 (0.6) Lump 6.2 (0.8) 16.7 (0.5) Rearing rank Single (Reference) No lambs 8.3 (0.8) 7.4 (0.5) Twins 0.2 (0.84) 0.7 NS (0.5) Triplets 0.9 NS (1.2) 1.3 NS (0.9) Constant 0.009 0.01 (0.4) weaning Pre-mating udder half defect Normal (Reference) - - Hard 84.7 (0.7) 76.0 (0.5) Lump 9.4 (1.1) 20.8 (0.5) Constant 0.006 (0.3) 0.02 (0.19) Note: All relative risk ratios (RRR) were significant (p < 0.05), except those designated as NS (not significant, p > 0.05). animals-13-00784-t003_Table 3 Table 3 Predicted probability (Pp) of udder half defect occurrence in non-dairy Romney ewes at pre-lambing, docking, and weaning based on pre-mating udder half defect category from 1962 udder halves (981 ewes) in 2017 and 1538 udder halves (769 ewes) in 2018 (Study A). Year Pre-Mating Udder Half Defect Category Change of Udder Half Defect Category Pre-Lambing Docking Weaning 2017 Normal Normal to Normal 0.987 0.968 0.959 Normal to Hard 0.002 0.012 0.005 Normal to Lump 0.024 0.020 0.036 Hard Hard to Normal 0.821 0.834 0.727 Hard to Hard 0.036 0.149 0.182 Hard to Lump 0.143 0.017 0.091 Lump Lump to Normal 0.797 0.608 0.714 Lump to Hard 0.060 0.323 0.107 Lump to Lump 0.143 0.069 0.179 2018 Normal Normal to Normal 0.999 0.969 0.973 Normal to Hard 0.001 * 0.010 0.001 * Normal to Lump 0.001 * 0.020 0.021 Hard Hard to Normal 0.333 0.160 0.320 Hard to Hard 0.333 0.440 0.160 Hard to Lump 0.333 0.400 0.520 Lump Lump to Normal 0.786 0.630 0.703 Lump to Hard 0.036 0.074 0.001 * Lump to Lump 0.178 0.296 0.296 Note: * indicates probability of 0.001 or less. A Predicted probability (Pp) of 0 indicates the impossibility of the defect category occurring, and 1 indicates certainty. animals-13-00784-t004_Table 4 Table 4 Predicted relative risk ratio (RRR +- standard error) of 2018 pre-mating udder half defect occurrence based on 2017 pre-mating and weaning udder half defect status from 1408 udder halves (from 704 non-dairy Romney ewes) (Study A). Predictor Variables Categories Pre-Mating Udder Half Defect (2018) Hard Lump 2017 Pre-mating udder half defect Normal (Reference) Hard 15.4 (0.6) 7.6 (0.8) Lump 6.6 (0.8) 13.4 (0.6) Pre-mating BCS 0.3 (0.4) 0.4 (0.4) Ewe age (Year born) 2013 (Reference) 2014 1.3 NS (0.4) 4.7 (0.6) Constant 0.4 NS (1.3) 0.1 NS (1.4) 2017 Weaning udder half defect Normal (Reference) Hard 141.2 (0.62) 53 (0.8) Lump 5.9 (0.5) 15.7 (0.5) Constant 0.011 (0.2) 0.011 (0.2) Note: All Relative Risk Ratios were significant (p < 0.05), except those designated as NS (not significant, p > 0.05). animals-13-00784-t005_Table 5 Table 5 Predicted probability (Pp) of udder half defects change over time from Day 7 to 42 of lactation based on pre-mating udder half defect category in 92 udder halves (from 46 non-dairy Romney ewes; Study B). Udder Half Defect Category Day 7 Day 14 Day 21 Day 28 Day 35 Day 42 Pre-Mating Lactation Normal Normal 0.864 0.674 0.904 0.986 0.961 0.883 Hard 0.113 0. 107 0.037 0.001 * 0.001 * 0.067 Lump 0.023 0.220 0.060 0.014 0.039 0.050 Hard |= Normal 0.907 0.001 * 0.674 0.297 0.001 * 0.001 * Hard 0.093 0.001 * 0.001 * 0.001 * 0.001 * 0.001 * Lump 0.001 * 0.999 0.326 0.999 0.999 0.999 Lump Normal 0.574 0.708 0.804 0.923 0.616 0.500 Hard 0.396 0.090 0.021 0.001 * 0.001 * 0.056 Lump 0.030 0.201 0.175 0.077 0.384 0.444 Note: The Predicted probability of each udder half defect category in the six examinations during lactation (Day 7 to Day 42) was undertaken based on the pre-mating udder half defect status of the ewes. |= Only three udder halves were categorised as hard at pre-mating. * indicates probability of 0.001 or less. A Predicted probability (Pp) of 0 indicates the impossibility of the defect category occurring and 1 indicates certainty. 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PMC10000214 | Equine leaky gut syndrome is characterized by gastrointestinal hyperpermeability and may be associated with adverse health effects in horses. The purpose was to evaluate the effects of a prebiotic Aspergillus oryzae product (SUPP) on stress-induced gastrointestinal hyperpermeability. Eight horses received a diet containing SUPP (0.02 g/kg BW) or an unsupplemented diet (CO) (n = 4 per group) for 28 days. On Days 0 and 28, horses were intubated with an indigestible marker of gastrointestinal permeability (iohexol). Half the horses from each feeding group underwent 60 min of transport by trailer immediately followed by a moderate-intensity exercise bout of 30 min (EX), and the remaining horses stayed in stalls as controls (SED). Blood was sampled before iohexol, immediately after trailering, and at 0, 1, 2, 4, and 8 h post-exercise. At the end of the feeding period, horses were washed out for 28 days before being assigned to the opposite feeding group, and the study was replicated. Blood was analyzed for iohexol (HPLC), lipopolysaccharide (ELISA), and serum amyloid A (latex agglutination assay). Data were analyzed using three-way and two-way ANOVA. On Day 0, the combined challenge of trailer transport and exercise significantly increased plasma iohexol in both feeding groups; this increase was not seen in SED horses. On Day 28, EX increased plasma iohexol only in the CO feeding group; this increase was completely prevented by the provision of SUPP. It is concluded that combined transport and exercise induce gastrointestinal hyperpermeability. Dietary SUPP prevents this and therefore may be a useful prophylactic for pathologies associated with gastrointestinal hyperpermeability in horses. leaky gut syndrome horses hyperpermeability prebiotics BioZyme Inc.054839 OMAFRAUG-T2-2020-100854 This research was funded by BioZyme Inc. (Grant Number 054839), and access to horses was subsidized by OMAFRA (Grant Number UG-T2-2020-100854). pmc1. Introduction Leaky gut syndrome (LGS) is characterized by gastrointestinal hyperpermeability and increased accessibility of the systemic environment to compounds that are normally sequestered within the gastrointestinal lumen . The contribution of LGS to equine disease is poorly understood, and its mitigation by dietary interventions has not been described in the literature. An MSc thesis from Michigan State University describes a study in which oral phenylbutazone contributed to the development of gastrointestinal hyperpermeability in 18 Arabian horses, suggesting that gastric ulceration, phenylbutazone administration, or both, contribute to the development of LGS in horses. Evidence also implicates diets high in starch as complicit in gastrointestinal hyperpermeability . Exercise is another likely candidate as an LGS risk factor but has not been clearly described in horses. Research in humans, however, provides evidence for a positive correlation between exercise intensity/duration and hyperpermeability of the gastrointestinal tract . A recent study in eight horses reports that the combination of exercise and trailer transport induces an increase in gastrointestinal permeability, as well as increased serum amyloid A and lipopolysaccharide . Whilst the pathophysiological consequences of LGS are as vaguely characterized as its triggers, there is evidence that, depending on the degree of inflammatory response to luminal toxins, LGS may impair skeletal muscle metabolism , and contribute to metabolic dysfunction , allergies , and inflammatory diseases such as arthritis . Dietary interventions with evidence for an ability to protect against the development or clinical consequences of LGS will make an important contribution to preserving robust equine health. Perhaps due (at least in part) to the incomplete picture defining the cause-and-effect of LGS, interventions tend to rely heavily on the management of downstream clinical consequences. To the authors' knowledge, there are currently no feed supplements or pharmaceutical drugs that have been evaluated against the gastrointestinal hyperpermeability that is the cornerstone of LGS. A commonly reported feature of LGS in non-equine species is gastrointestinal dysbiosis, and there is evidence that this dysbiosis contributes to the development of hyperpermeability . Dysbiosis is likely in horses receiving a high-starch diet , and in horses experiencing physiological stress . Thus, interventions with potential to stabilize gastrointestinal microbiota may protect against the development of hyperpermeability under conditions of stress. Aspergillus oryzae is a filamentous fungus, which has demonstrated the ability to amplify the abundance of probiotic microbes (particularly Bifidobacterium pseudolongum) whilst protecting DSS-challenged mice against colitis . The fermentation product of A. oryzae also promotes fiber-degrading bacteria in the rumen and hindgut when fed to lactating dairy cows . In addition to evidence for a prebiotic-like effect, A. oryzae also exerts a marked anti-inflammatory effect in LPS-stimulated polymorphonuclear cells and improves the structure of gastrointestinal lumen (i.e., villus height-crypt ratio) in broiler chickens . Furthermore, the administration of a postbiotic from A. oryzae to calves prevented the increase in intestinal permeability associated with exposure to high ambient temperature . These data support the hypothesis that A. oryzae protects against stress-induced hyperpermeability by amplifying the abundance of a healthy gastrointestinal microbiome. Accordingly, the purpose of the current study was to evaluate the effects of a fungal prebiotic produced through a proprietary fermentation process with A. oryzae (SUPP; BioZyme Inc.; St. Joseph, MO, USA) on equine gastrointestinal hyperpermeability induced by a combination of trailer transport and moderate-intensity exercise horses. The objectives were to characterize the effect of a dietary A. oryzae prebiotic on the appearance and disappearance of an oral permeability marker (iohexol) in the blood of horses challenged with combined transport and exercise stress, and to correlate observed effects with those on downstream evidence of inflammation (serum amyloid A (SAA)) and translocation of enteric endotoxin (lipopolysaccharide (LPS)). 2. Materials and Methods Care and use of animals was reviewed and approved by the University of Guelph Animal Care Committee in compliance with the guidelines published by the Canadian Council on Animal Care (Approval Number 3800). 2.1. Horses Eight (8) healthy mares (Age: 14.2 +- 3.7 years; body weight: 570 +- 47.4 kg) from the Arkell Equine Research Station, University of Guelph, were included in the randomized, partial cross-over trial. The horses were group-housed in an open turnout area, with unrestricted access to a large covered shelter bedded with straw, 1st cut Timothy hay, water, and trace mineral salt. Two hundred and fifty (250) g of a 12% maintenance pellet rationa was provided once per day (morning) (Table 1). Horses were all accustomed to a lifestyle that did not include forced exercise. At the beginning of the study, all 8 horses were randomized into one of two feeding groups (n = 4 per group): Group A: unsupplemented control diet (CO); Group B: diet containing A. oryzae prebioticb (SUPP; 0.02 g/kg BW). SUPP was a textured, unpelleted product and was top-dressed onto the horse's individual pelleted feed once per day. Horses consumed their pelleted ration with or without SUPP once per day in individual stalls. Once their feed was completely consumed, they were returned to the outdoor turnout area. Within each feeding group, horses were further divided into stress-challenged (EX--see below for details) or non-challenged sedentary controls (SED) (n = 2 per group per replicate). Horses received their assigned diet for 28 days. On Days 0 and 28, one SED and one EX horse were evaluated in the morning, and a second SED and second EX horse were evaluated in the afternoon. At the end of the 28-day feeding period, horses were washed out for 28 days, and then assigned to the opposite feeding group for an additional 28 days. The trial was then repeated, for a final 'n' of 8 per feeding group (i.e., 4 x EX and 4 x SED per feeding group). Horses were tested at the same time of day (morning or afternoon) in both study periods. On study days, horses remained in their turnout area with unrestricted water access, but from which all feed had been removed. Following 12 h of fasting, horses were stalled and administered via nasogastric tube an indigestible marker of gastrointestinal permeability (iohexolc; 5.6% solution, 1.0 mL/per kg BW; 56 mg/kg BW) by a licensed veterinary professional . The procedure was conducted in the absence of any sedation, so as not to interfere with normal gastrointestinal motility . 2.2. Stress Challenge Horses were challenged with combined trailer transport and exercise, which we have previously demonstrated to produce a measurable and significant increase in gastrointestinal hyperpermeability . Briefly, following the administration of iohexol, one EX horse was walked onto a 2-horse trailer for a 60 min drive to the Equine Sports Medicine and Reproduction Centre, University of Guelph. Once at the facility, a heart rate (HR) monitord was attached to the horse using a flexible belly-band, and the horse was free-lunged around an indoor arena (5 min' walk, 10 min trot (left), 10 min trot (right), and 5 min' walk) on a sand footing for 30 min. Horses were encouraged to achieve an exercise intensity that resulted in a HR of approximately 150 bpm during the trot, in order to encourage the horse to work at or beyond the anaerobic threshold . At the cessation of exercise, EX horses returned to the group housing yard directly and were turned out with unrestricted access to hay and water. This challenge has previously been demonstrated to produce gastrointestinal hyperpermeability in horses . Following the application of topical lidocaine at the jugular groove, blood was sampled from the jugular vein immediately before iohexol administration (P1), immediately after trailering (P2), immediately after exercise (P3), and then 1 (P4), 2 (P5), 4 (P6), and 8 h (P7) post-exercise. Blood samples were cooled on ice, centrifuged within 2 h of collection, and the recovered plasma was frozen (-20 degC) until analysis. Manure samples were collected within 2 min of voiding before the horse walked into the trailer, at the end of 60 min of transport, and the first manure after exercise. 2.3. Non-Challenged Controls SED horses received iohexol at the same time as the EX horses, and blood was sampled at the same time as the EX horses. After receiving iohexol they were returned to the group housing area with free access to water. Hay was provided upon return of the EX horse from transport and exercise. 2.4. Sample Analysis All chemicals and reagents were purchased from Sigma Aldrichf, unless otherwise stated. Plasma samples were analyzed for systemic inflammation (serum amyloid A and lipopolysaccharide (LPS)) biomarkers, and an exogenous marker of gastrointestinal permeability (iohexol). Plasma iohexol was determined via HPLC (Agilent 1200 series HPLC gradient system), which was used to quantify plasma iohexol (m g/mL) with UV detection at 254 nm, as previously described ( inter-assay CV: 3.106 and 4.217%, respectively). SAA was determined by Eiken Serum Amyloid A latex agglutination assay at a commercial laboratory (Animal Health Laboratory, University of Guelph). Plasma samples, acclimated at room temperature, were analyzed in duplicate for LPS (pg/mL) using an equine-specific quantitative sandwich ELISA kit according to manufacturerh instructions ( intra-assay coefficient of variability: 1.5 and 1.6%, respectively). A standard curve was used to generate a linear regression equation, which was used to calculate LPS concentrations in each sample. 2.5. Data Analysis Data analysis was conducted using SigmaPloti (Version 14.2). Data are presented as mean +- SD unless otherwise indicated. Normality of data was determined using the Shapiro-Wilk test. Three-way ANOVA was used to detect interactions between feeding groups, stress challenge, and time after iohexol administration. Two-way ANOVA was used to identify significant differences between feeding groups in SED and EX horses on Day 0 and Day 28 with respect to stress challenge and time after iohexol administration. The Holm-Sidak post-hoc test was used to identify significantly different means when a significant F-ratio was calculated. Significance was accepted at p < 0.05. 3. Results 3.1. Gastrointestinal Barrier Function 3.1.1. Control Diet Day 0: In SED horses receiving the CO diet, there was no significant change in plasma iohexol at any time between P1 (0.56 +- 0.02 ug/mL) and P7 (0.69 +- 0.04 ug/mL) (p = 0.26). EX horses demonstrated a significant increase in plasma iohexol between P1 (0.52 +- 0.03 ug/mL) and P3 (1.14 +- 0.08 ug/mL) (p = 0.02). Plasma iohexol was significantly higher in EX horses than in SED horses at P2 (SED: 0.71 +- 0.06 ug/mL; EX: 1.02 +- 0.18 ug/mL) (p = 0.04) and P3 (SED: 0.75 +- 0.09 ug/mL; EX: 1.14 +- 0.08 ug/mL) (p = 0.01) . Day 28: In SED horses receiving the CO diet, there was no significant change in plasma iohexol at any time between P1 (0.48 +- 0.04 ug/mL) and P7 (0.60 +- 0.06 ug/mL) (p = 0.44). EX horses demonstrated a significant increase in plasma iohexol between P1 (0.58 +- 0.09 ug/mL) and P3 (1.07 +- 0.06 ug/mL) (p = 0.006). Plasma iohexol was significantly higher in EX horses than in SED horses at P2 (SED: 0.54 +- 0.06 ug/mL; EX: 1.01 +- 0.12 ug/mL) (p < 0.001), P3 (SED: 0.56 +- 0.07 ug/mL; EX: 1.07 +- 0.12 ug/mL) (p < 0.001) and P4 (SED: 0.59 +- 0.04 ug/mL; EX: 1.00 +- 0.10 ug/mL) (p < 0.001) . Day 0 vs. Day 28: In SED horses, plasma iohexol was significantly higher on Day 0 than on Day 28 at P3 and P5 (p = 0.04 and 0.05, respectively). There were no significant differences between Day 0 and Day 28 in EX horses (p = 0.23) . 3.1.2. Supplemented Diet Day 0: In SED horses receiving the SUPP diet, there was a significant increase in plasma iohexol between P1 (0.51 +- 0.03 ug/mL) and P2 (0.87 +- 0.04 ug/mL) (p = 0.005), P3 (0.82 +- 0.06 ug/mL) (p = 0.02) and P4 (0.97 +- 0.09 ug/mL) (p < 0.001). EX horses demonstrated a significant increase in plasma iohexol between P1 (0.70 +- 0.15 ug/mL) and P3 (1.75 +- 0.19 ug/mL) (p = 0.01). Plasma iohexol was significantly higher in EX horses than in SED horses at P3 (SED: 0.82 +- 0.06 ug/mL; EX: 1.75 +- 0.19 ug/mL) (p < 0.001) . Day 28: In SED horses receiving the SUPP diet, there was no significant change in plasma iohexol at any time between P1 (0.49 +- 0.05 ug/mL) and P7 (0.70 +- 0.05 ug/mL) (p = 0.43). There was also no significant increase in plasma iohexol in EX horses at any time between P1 (0.87 +- 0.23 ug/mL) and P7 (0.56 +- 0.12 ug/mL) (p = 0.36) . 3.1.3. Day 0 and Day 28 in Supplemented and Control Diets On Day 0, iohexol tended to be higher in SUPP than CO horses (p = 0.053). Overall iohexol was significantly elevated in EX horses at P2, P3, (p < 0.001) and P4 (p = 0.02) compared with P1, but there were no differences between treatment groups On Day 28, iohexol was significantly higher overall in CO horses compared with SUPP horses (p = 0.008). Overall, iohexol was significantly higher at P3 than P1, but there were no significant differences between treatment groups . 3.2. Systemic Inflammation 3.2.1. Serum Amyloid A (SAA; Table 2) Control Diet Day 0: In SED horses receiving the CO diet, there was no significant change in SAA at any time between P1 (0.10 +- 0.1 mg/mL) and P7 (0.10 +- 0.1 mg/mL) (p = 0.78). There was also no significant change in EX horses in SAA between P1 (0.22 +- 0.16 mg/mL) and P7 (0.86 +- 0.56 mg/mL) (p = 0.70). Overall, SAA was significantly higher in EX than in SED horses (p = 0.01), but there were no significant differences between groups at any specific time point (Table 2). Day 28: In SED horses receiving the CO diet, there was no significant change in SAA at any time between P1 (0.0 +- 0.0 mg/mL) and P7 (0.10 +- 0.10 mg/mL) (p = 0.92). There was also no significant change in EX horses in SAA between P1 (0.15 +- 0.15 ug/mL) and P7 (0.20 +- 0.20 mg/mL) (p = 0.96). In horses receiving the CO diet, SED horses had significantly lower SAA than EX horses overall (p = 0.04), but there were no significant differences at individual time points (Table 2). Supplemented Diet Day 0: In SED horses receiving the SUPP diet, there was no significant change in SAA at any time between P1 (0.33 +- 0.33 mg/mL) and P7 (0.15 +- 0.15 mg/mL) (p = 0.71). There was also no significant change in EX horses SAA between P1 (0.08 +- 0.08 mg/mL) and P7 (0.30 +- 0.30 mg/mL) (p = 0.70). There were no significant differences between SED and EX at any specific time point on Day 0 (Table 2). Day 28: In SED horses receiving the SUPP diet, there was no significant change in SAA at any time between P1 (0.17 +- 0.17 mg/mL) and P7 (0.35 +- 0.15 mg/mL) (p = 0.59). There was also no significant change in EX horses in SAA between P1 (0.35 +- 0.25 mg/mL) and P7 (1.00 +- 0.53 mg/mL) (p = 0.96). Overall, SAA was significantly higher in EX than in SED horses (p = 0.02), but there were no significant differences between groups at specific time points (Table 2). Day 0 and Day 28 in Supplemented and Control Diets On Day 0, there were no differences in SAA between SUPP and CO horses (p = 0.257). Overall, SAA was significantly higher in EX than SED horses (p = 0.015), primarily owing to significantly higher SAA in EX than SED horses in CO horses (p = 0.002) that was not observed in SUPP horses (p = 0.826) (Table 2). On Day 28, SAA was significantly higher overall in SUPP horses compared with CO horses (p = 0.01). There was no significant difference in SAA between EX and SED horses overall, but SAA was significantly higher in SED horses than EX horses in horses receiving the supplemented diet (p = 0.05) (Table 2). 3.2.2. Lipopolysaccharide (LPS; Table 2) Control Diet Day 0: In SED horses receiving the CO diet, there was no significant change in LPS at any time between P1 (2.10 +- 0.09 pg/mL) and P7 (2.13 +- 0.12 pg/mL) (p = 0.71). There was also no significant change in EX horses in LPS between P1 (2.18 +- 0.06 pg/mL) and P7 (2.21 +- 0.10 pg/mL) (p = 0.99). Overall, LPS was significantly higher in EX than in SED horses (p = 0.02), but there were no significant differences between SED and EX at any specific time point (Table 2). Day 28: In SED horses receiving the CO diet, there was no significant change in LPS at any time between P1 (2.1 +- 0.09 pg/mL) and P7 (2.1 +- 0.05 pg/mL) (p = 0.94). There was also no significant change in EX horses in LPS between P1 (2.14 +- 0.03 pg/mL) and P7 (2.10 +- 0.08 pg/mL) (p = 0.94). Overall, LPS was significantly higher in EX than in SED horses (p = 0.004), but there were no significant differences between groups at specific time points (Table 2). Supplemented Diet Day 0: In SED horses receiving the SUPP diet, there was no significant change in LPS at any time between P1 (2.15 +- 0.04 pg/mL) and P7 (2.17 +- 0.04 pg/mL) (p = 0.91). There was also no significant change in EX horses LPS between P1 (2.06 +- 0.04 pg/mL) and P7 (2.13 +- 0.01 pg/mL) (p = 0.98). LPS was significantly higher in SED than EX horses (p = 0.03), but there were no significant differences between groups at specific time points (Table 2). Day 28: In SED horses receiving the SUPP diet, there was no significant change in LPS at any time between P1 (2.20 +- 0.08 pg/mL) and P7 (2.18 +- 0.07 pg/mL) (p = 0.90). There was also no significant change in EX horses in LPS between P1 (2.06 +- 0.04 pg/mL) and P7 (2.06 +- 0.05 pg/mL) (p = 0.97). LPS was significantly higher in SED than EX horses overall (p < 0.001), as well as at P5 (p = 0.01) and P6 (p = 0.05) (Table 2). Day 0 and Day 28 in Supplemented and Control Diets On Day 0, there were no differences in LPS between SUPP and CO horses (p = 0.346). There was also no significant difference between EX and SED horses overall (p = 0.268). LPS was significantly higher in EX than SED horses in the CO group (p = 0.003), but there were no significant differences in LPS between EX and SED horses in the SUPP group (p = 0.068) (Table 2). On Day 28, there were no differences in LPS between SUPP and CO horses (p = 0.674). There was also no significant difference between EX and SED horses overall (p = 0.392). LPS was significantly higher in EX than SED horses in the CO group (p = 0.004) and significantly lower in EX than SED in the SUPP group (p < 0.001) (Table 2). 4. Discussion The purpose of the current study was to quantify the effect of a dietary A. oryzae prebiotic on gastrointestinal permeability in horses challenged with combined transport and exercise stress. The main finding was that 28 days of supplementation with the A. oryzae prebiotic completely eradicated stress-induced gastrointestinal permeability in this group of horses. We have previously demonstrated that the combination of transport and exercise stress model utilized in the current study produces gastrointestinal hyperpermeability and an increase in blood biomarkers that evidence transient, low-grade systemic inflammation . Like our previous study, we report herein that 60 min of trailer transport immediately preceding half an hour of moderate-intensity exercise is a clear, reproducible model of gastrointestinal hyperpermeability. On Day 0 for both feeding groups, the stress model resulted in a significant uptick in the systemic appearance of orally administered iohexol that was not seen in unstressed controls. That this spike in the systemic appearance of iohexol was absent in stressed horses in the SUPP feeding group on Day 28 provides strong evidence for the role of A. oryzae prebiotic in protecting gastrointestinal barrier function in horses during stress. The mechanism for this blockade is not known but may be associated with an effect of A. oryzae prebiotic on the enteric microbiome. A. oryzae strongly increases the relative abundance of anti-inflammatory bacterial strains such as Bifidobacterium and important fiber-degrading bacteria such as Ruminococcaceae . Dietary provision of Bifidobacterium-based probiotics to obese humans results in a marked decrease in gastrointestinal hyperpermeability , which provides support for the hypothesis that A. oryzae prebiotic protects the enteric barrier from stress-induced hyperpermeability via its modulation of the gastrointestinal microbiome. This hypothesis should be tested in future studies. When dietary groups were combined, there was an overall increase in SAA in response to our stress challenge, consistent with our previous study , but this effect was not observed when analyzing dietary groups individually. SAA is the major acute phase protein in the horse. While it is a highly sensitive indicator of an inflammatory event, it is not specific, and its production can be markedly increased in the presence of almost any inflammatory challenge . The vast majority of SAA is produced by hepatocytes, but small amounts may also be produced by enterocytes . Our small sample size, together with SAA fluctuations in both EX and SED groups that were unrelated to our stress challenge, likely contributed to the lack of statistical increase in SAA within groups. Consequently, the effect of A. oryzae prebiotic on this biomarker remains unknown. Owing to the highly plastic nature of SAA in vivo, future studies to evaluate the effects of the A. oryzae prebiotic on this outcome measure may benefit from controlled in vitro assessment of enterocyte-specific production of SAA . The marked gastrointestinal hyperpermeability that was observed in the current study in EX horses in the control feeding group on Days 0 and 28 was not associated with a significant time-dependent increase in circulating LPS, and like SAA, this may have been due, at least in part, to our small sample size. But the overall serum LPS concentration of EX horses was significantly higher than SED horses. Surprisingly, however, serum LPS was significantly lower in EX than in SED horses for the A. oryzae feeding group. This result is probably not associated with the supplement because it was observed both on Day 0 (prior to beginning supplementation) and on Day 28, so instead is more likely an artifact of randomizing a small number of animals to the feeding groups. Furthermore, our maximum LPS concentration of 2.24 pg/mL in either feeding group is well within the reference interval for the normal flux of systemic LPS in healthy horses . Future studies designed to detect the effect of the dietary A. oryzae prebiotic on the translocation of enteric LPS at levels expected to be associated with disease will require a stronger stress challenge such as non-steroidal anti-inflammatory drugs . The current study had fewer animals in each treatment group than our previous study, which may have resulted in the current study being underpowered to detect the effects of stress and/or diet on SAA and LPS. 5. Conclusions In conclusion, the data presented herein provide compelling evidence for a protective effect of A. oryzae prebiotic on stress-induced gastrointestinal hyperpermeability. This supplement may be a useful dietary ingredient for horses undergoing combined transport and exercise stress as a prevention for gastrointestinal hyperpermeability. Future studies should explore the effects of A. oryzae prebiotic on the equine gastrointestinal microbiome as a potential mode of action. Author Contributions Conceptualization, W.P.; methodology, M.M., S.M., A.A., K.N.H., Y.L., E.J.S. and W.P. data curation, W.P.; writing--original draft preparation, W.P.; writing--review and editing, W.P., M.M., S.M., A.A., K.N.H., Y.L., E.J.S. and L.W.; supervision, W.P.; project administration, W.P.; funding acquisition, W.P. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was conducted in accordance with the Canadian Council on Animal Care, and approved by the Animal Care Committee of The University Of Guelph (Protocol Code 3800, 2020). Informed Consent Statement Not applicable. Data Availability Statement All processed data, final data, and figures will be available for sharing within the University of Guelph via the Agri-environmental research data repository. For access outside the University, users can contact the PI for special access to data. Conflicts of Interest This study received funding from Biozyme Inc. L.W. is employed by Biozyme Inc. and had the following involvement in the study and writing--review and editing. All other authors declare no competing interests. Figure 1 Plasma iohexol (mg/mL). Horses (n = 8) on the CO diet were administered an oral dose of iohexol (5.6% solution; 1 mL/kg BW) immediately prior to one hour of trailer transport followed by 30 min of moderate-intensity exercise (EX) on Day 0 (Panel (A)) and Day 28 (Panel (B)). Unchallenged horses (SED; n = 8) were maintained in stalls as controls and sampled at the same time intervals. Blood was sampled prior to iohexol administration (P1), immediately after trailering (P2), immediately after exercise (P3), and 1 (P4), 2 (P5), 4 (P6), and 8 h post-exercise (P7). * denotes significant change from baseline within a group; different letters denote significant differences between groups at a given time point. Figure 2 Plasma iohexol (mg/mL). Horses (n = 8) on the SUPP diet were administered an oral dose of iohexol (5.6% solution; 1 mL/kg BW) immediately prior to one hour of trailer transport followed by 30 min of moderate-intensity exercise (EX) prior to supplementation (Panel A) and after 28 days of supplementation (Panel B). Unstressed horses (SED; n = 8) were maintained in stalls as controls and sampled at the same time intervals. Blood was sampled prior to iohexol administration (P1), immediately after trailering (P2), immediately after exercise (P3), and 1 (P4), 2 (P5), 4 (P6), and 8 h post-exercise (P7). * denotes significant change from baseline within a group; different letters denote significant differences between groups at a given time point. animals-13-00951-t001_Table 1 Table 1 Horse ration pellets (12%). Nutritional Analysis (as Fed) Crude Protein 11.99% Lysine 0.49% Crude Fat 3.60% Crude Fiber 9.34% Dry Matter 89.09% Calcium (total) 0.74% Phosphorus (total) 0.52% Sodium 0.35% Chloride 0.53% Potassium 0.72% Magnesium 0.29% Sulfur 0.15% Iron 110.71 mg/kg Manganese 150.26 mg/kg Zinc 182.22 mg/kg Copper 36.46 mg/kg Iodine 0.98 mg/kg Selenium 0.40 mg/kg Cobalt 3.00 mg/kg Vitamin A 12.53 KIU/kg Vitamin D3 2.51 KIU/kg Vitamin E 200.00 KIU/kg Biotin 1640.00 mcg/kg D.E. Horse 3.06 Mcal/kg TDN Horse 72.31% Starch 23.21% animals-13-00951-t002_Table 2 Table 2 Serum amyloid A (SAA; ug/mL +- SEM) and Lipopolysaccharide (LPS; pg/mL +- SEM) in horses challenged with combined transport and exercise (EX) or maintained as unchallenged controls (SED), before (Day 0) or 28 days after (Day 28) receiving a diet containing an Aspergillus oryzae prebiotic (SUPP) or a control diet (CO). SAA LPS Day 0 CO SUPP CO SUPP SED a EX b p ** SED EX p ** SED a EX b p ** SED b EX a p ** P1 0.10 +- 0.10 0.22 +- 0.16 0.9 0.33 +- 0.33 0.08 +- 0.08 0.8 2.10 +- 0.09 2.18 +- 0.06 1.0 2.15 +- 0.04 2.06 +- 0.04 1.0 P2 0.03 +- 0.03 0.12 +- 0.10 0.9 0.03 +- 0.03 0.00 +- 0.00 0.8 2.09 +- 0.06 2.23 +- 0.06 1.0 2.14 +- 0.02 2.09 +- 0.02 1.0 P3 0.00 +- 0.00 0.52 +- 0.24 0.9 0.10 +- 0.10 0.23 +- 0.17 0.8 2.14 +- 0.06 2.22 +- 0.10 1.0 2.16 +- 0.05 2.13 +- 0.04 1.0 P4 0.00 +- 0.00 0.46 +- 0.30 0.9 0.20 +- 0.20 0.03 +- 0.03 0.8 2.10 +- 0.06 2.24 +- 0.13 1.0 2.19 +- 0.03 2.11 +- 0.05 1.0 P5 0.03 +- 0.03 0.74 +- 0.43 0.9 0.18 +- 0.18 0.10 +- 0.10 0.8 2.08 +- 0.04 2.19 +- 0.05 1.0 2.15 +- 0.04 2.10 +- 0.05 1.0 P6 0.03 +- 0.03 0.78 +- 0.45 0.9 0.08 +- 0.08 0.00 +- 0.00 0.8 2.09 +- 0.04 2.24 +- 0.08 1.0 2.18 +- 0.01 2.14 +- 0.05 1.0 P7 0.10 +- 0.10 0.86 +- 0.56 0.9 0.15 +- 0.15 0.30 +- 0.30 0.8 2.13 +- 0.12 2.21 +- 0.10 1.0 2.17 +- 0.04 2.13 +- 0.01 1.0 p * 0.78 0.70 0.92 0.96 0.71 0.99 0.91 0.98 Day 28 CO SUPP CO SUPP SED a EX b p ** SED EX p ** SED a EX b p ** SED b EX a p ** P1 0.00 +- 0.00 0.15 +- 0.15 1.0 0.17 +- 0.17 0.35 +- 0.25 0.8 2.10 +- 0.09 2.14 +- 0.03 0.68 2.20 +- 0.08 2.06 +- 0.04 0.11 P2 0.00 +- 0.00 0.15 +- 0.12 1.0 0.07 +- 0.07 0.50 +- 0.50 0.8 2.04 +- 0.04 2.15 +- 0.05 0.20 2.15 +- 0.08 2.04 +- 0.04 0.22 P3 0.00 +- 0.00 0.23 +- 0.17 1.0 0.23 +- 0.15 0.47 +- 0.37 0.8 2.07 +- 0.07 2.17 +- 0.05 0.26 2.13 +- 0.05 2.03 +- 0.03 0.26 P4 0.00 +- 0.00 0.08 +- 0.05 1.0 0.07 +- 0.07 1.33 +- 1.00 0.8 2.00 +- 0.05 2.17 +- 0.04 0.05 2.16 +- 0.07 2.05 +- 0.05 0.20 P5 0.03 +- 0.03 0.23 +- 0.23 1.0 0.03 +- 0.03 0.63 +- 0.41 0.8 2.04 +- 0.05 2.19 +- 0.07 0.10 2.24 +- 0.04 2.02 +- 0.03 0.01 P6 0.03 +- 0.03 0.35 +- 0.22 1.0 0.13 +- 0.09 0.45 +- 0.45 0.8 2.08 +- 0.08 2.18 +- 0.08 0.25 2.24 +- 0.10 2.06 +- 0.04 0.05 P7 0.10 +- 0.10 0.20 +- 0.20 1.0 0.35 +- 0.15 1.00 +- 0.53 0.8 2.07 +- 0.05 2.10 +- 0.08 0.68 2.18 +- 0.07 2.06 +- 0.05 0.17 p * 0.92 0.96 0.71 0.70 0.94 0.94 0.90 0.97 P1: before iohexol administration; P2: immediately after 1 h of trailer transport; P3 immediately after 30 min of moderate-intensity exercise; P4: after 1 h of exercise recovery; P5: after 2 h of exercise recovery; P6: after 4 h of exercise recovery; P7: after 8 h of e after 8 h of exercise recovery; different lower-case letters denote significant differences between SED and EX overall; p * = p-values for one-way ANOVA within treatment group; p ** p-values for 2-way ANOVA time x treatment group within diet. 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PMC10000215 | Large grazers are essential for nature conservation. In order to prevent grazers from moving to unintended areas, it may be necessary to keep them inside enclosures. Physical fences present a number of problems, such as fragmenting the landscape. Virtual fencing, however, is a possible replacement for physical fencing, making it possible to enclose grazers without physical boundaries. Virtual fencing systems utilise collars with GPS technology to track animals and deliver auditory warnings and electric impulses to keep animals within predefined boundaries. This study examines how effective the virtual fencing system Nofence(c) is at enclosing calves in a holistically managed setting. Holistic management is a rotational grazing technique where an enclosure is grazed in small strips at a time. It is investigated whether the calves become habituated to the virtual fence and whether there is a correlation between the number of warnings received by every two calves in order to explore potential herd behaviour. Finally, this study examines which calves interact the most with the virtual fence by investigating the relationship between physical activity and number of interactions. Seventeen calves were fitted with a GPS collar from the company Nofence(c) and placed in a holistically managed enclosure. Data were gathered from 4 July to 30 September 2022. The study found that virtual fence was able to contain calves inside the designated enclosure, and over time the calves received notably fewer electrical impulses compared to auditory warnings. The results of Pearson's correlation between auditory warnings received by two random calves were inconclusive, but the use of a sliding window analysis should be further explored. Lastly, the most physically active animals were the ones who received the most auditory warnings, but they did not receive more impulses. No significant correlation was found between the number of electric impulses received and the physical activity of the animals. animals virtual fencing grazing management Nofence(c) cattle holistic management 15. Juni Fonden, HedeselskabetMarkus Jebsens NaturpuljeThis research was funded by 15. Juni Fonden, Hedeselskabet and Markus Jebsens Naturpulje. We are grateful for the support, which made it possible to conduct this study. pmc1. Introduction Conservation of natural areas using grazers is required to reduce the loss of biodiversity . This often necessitates the use of physical fencing to keep grazers inside the desired area, as well as to prevent unwanted human encounters and traffic accidents . However, physical fencing presents a number of problems . Physical fences can thus have negative impacts on wildlife by creating artificial barriers in the landscape and limiting the free movement of other animals . These barriers can also lead to collisions, such as when low-flying bird species collide with fences with lethal consequences . An example of an affected species, which are comparable in size and ecology to native European red deer and fallow deer, are the North American white-tailed deer and mule deer, as described by Harrington et al., Burkholder et al. and Bishop et al. . These papers found that deer were prone to getting caught and dying when attempting to cross fences, with fence crossing success rates at around 75% and mortality rates upwards of 0.40/km/year for pasture fences . Moreover, physical fencing can be expensive to install and maintain . Even when fencing is used for nature conservation purposes, it can create new problems when trying to solve others, as physical fences fragment the landscape by preventing animals from moving around freely . Additionally, physical fencing poses a logistical and practical problem in terms of relocation . In some areas that are difficult to access or have challenging terrain, installing physical fences may not be feasible . Virtual fencing is a possible alternative to physical fencing, without many of the aforementioned problems of physical fencing . Virtual fencing is a GPS-based system that utilises auditory warnings and electrical impulses to keep livestock within a designated area. As the animal approaches the virtual boundary, warning signals and electrical impulses are administered by a collar fitted around the neck of each animal. This type of system is yet to be legalised in most countries in Europe, including Denmark, due to earlier concerns regarding animal welfare . However, several studies suggest that welfare is not compromised when utilising virtual fencing systems and livestock are effectively kept within enclosures . In a previous study on virtual fencing by Aaser et al. , it was hypothesised that a small enclosure size and regular moving of the virtual border could improve the effectiveness of virtual fencing systems. The reasoning behind the hypothesis was the cattle's constant interaction with the boundary, through which they would be reminded of the connection between warnings and impulses . According to the responsible veterinarian, the preliminary results of an experiment with holistically managed cattle on the island of Fano raised some concern, as the animals received a high number of warnings and impulses compared to animals kept in a larger stationary enclosure. Holistic management is a rotational grazing technique where an enclosure is grazed in small strips at a time. The strip is shifted a few metres at regular intervals, usually daily. To the best of our knowledge, little to no research has been conducted to examine the effectiveness of virtual fencing in a holistically managed setting. Cattle are, in general, gregarious and social creatures living in herds . They establish hierarchies, where some of the individuals lead the herd, while others are being lead . As suggested by by Aaser et al. , one might hypothesise that putting a collar on only some of the animals may be sufficient to keep the entire herd within a virtual enclosure, as has been shown to be the case for sheep . This could potentially help reduce the cost even further. The aim of this study was to investigate whether the Nofence(c) virtual fencing system is able to contain bull calves in a holistic management setting, whether the calves display herd behaviour and whether it is possible to predict which animals will interact most with the virtual boundary. To support this aim, the following four hypotheses were tested: (1) A virtual fence is capable of containing bull calves in a specific area during holistic management for more than 99% of the time. (2) Bull calves will receive fewer electrical impulses compared to warnings over time. (3) There is a positive correlation between the number of warnings received by any two bull calves in any given period. (4) Bull calves with the most physical activity receive the most warnings and impulses. 2. Materials and Method 2.1. Animals and Location This study took place on the Danish island of Fano. Seventeen Angus bull calves aged 9 to 12 months were placed in a holistically managed enclosure of 8.2 hectares . Some of these calves had previously been indirectly exposed to virtual fencing as their mothers were kept in another virtually fenced enclosure, though the bull calves themselves did not wear collars. The pasture was composed of flat cultural grassland. Due to the close proximity of a somewhat busy road, an electric fence was placed around the perimeter of the pasture. An artificial shelter and a water trough were provided in the northwestern side of the enclosure. Furthermore, the neighbouring farmer to the east had a herd of cattle adjacent to the pasture. 2.2. Virtual Fencing System Each animal was fitted with a cattle collar developed by Nofence(c). At the time of the experiment, each collar cost NOK 3050, while the system, regardless of the number of collars, cost a yearly digital service fee of NOK 669 (prices provided by Nofence(c) on 5 December 2022). The collars were the same as described by Aaser et al. . The collars were capable of registering five different types of messages with different information, which were sent to the official Nofence(c) server (Table 1). The position of the animal was logged every 15 min and the activity every 30 min. Activity was measured by a step counter developed for another species (sheep) and given as a unitless number. Whenever an animal received a warning or an electric impulse, or the fence status of the collar changed, this was logged at the time of the event along with the position of the animal. The different fence statuses are outlined in Table 2. With every message, the unique serial number of the collar was included. This number was used to reference the animal to which the collar was fitted. Each animal wore the same collar throughout the experiment. 2.3. Experimental Protocol The experiment began on 4 July 2022 and included seventeen Angus bull calves. Each calf was fitted with a collar and was let onto the western side of the field. During the initial days of the experiment, the calves were restricted to an inner enclosure of about 1 ha by an electric fence (Appendix B). This inner enclosure explains why the calves are located to the west during the beginning of the experiment (Appendix B). The virtual boundary was placed close to the electric fence, allowing the animals to receive auditory warnings when approaching the electric fence. The collars also administered electric impulses if the animals continued to move towards the electric fence after receiving a warning. On 9 July, one side of the internal fence was removed, meaning the calves would have to respect the virtual boundary to stay within the enclosure. On 10 July, the other side of the internal fence was removed, and on 11 July, all internal fences were removed. On 12 July, the enclosure size was doubled to 2 ha based on an assessment of the veterinarian associated with the project. At regular intervals, usually around every 24 h, the virtual enclosure was shifted 10-20 m. The fence was shifted eastwards in a circular motion, anchored at the water trough and resting shelters, until the physical boundary of the field was reached after 15 shifts and the procedure started over from the western boundary again (Appendix A). This method was used in order to maintain a balanced grazing intensity. Data collection began on 4 July 2022 and ended on 30 September 2022, totalling a period of 89 days. 2.4. Data and Statistical Analysis All data were downloaded from the official Nofence(c) servers. Five different message types, sent by the collars, were given as point data, and the virtual enclosure history was given as a polygon for each enclosure version. The start time and end time of each version of the enclosure was recorded. Poll messages were sent every 15 min and recorded the position of the animal, the time and the battery voltage in centivolts. Seq messages were sent every 30 min and described the activity of the animal and the solar charge accumulated by the collar in the last 30 min. Warning and Zap messages were sent whenever a warning or an electric impulse had been delivered to the animal. These messages provided the time and position of the animal. Warning messages also provided the length of the warning in milliseconds. Status messages were sent whenever the fence status of the collar changed, such as when an animal had escaped the enclosure (see Table 2). A total of 241,163 data points were collected. A total of 151,576 were Poll messages, 71,990 were Seq messages, 13,906 were Warning messages, 2153 were Status messages and 1538 were Zap messages. The data were subdivided by message type and individual. QGIS was used to plot and sort the data, while all statistical analyses were carried out in R version 4.0.3 . Only non-parametric tests were used, as the data did not follow a normal distribution. The collar fell off once for three of the calves, all in the month of August. One was refitted on the same day, while the other two were refitted after two and six days, respectively. 2.4.1. Effectiveness of Virtual Fencing To evaluate the effectiveness of the virtual fencing system, the number of Poll messages with the fence status Normal was compared to the number of Poll messages with fence status MaybeOutOfFence and fence status Escaped:NormalNormal+MaybeOutOfFence+Escaped Messages with the status MaybeOutOfFence were included to err on the side of caution with regard to the amount of time animals spent outside the enclosure. To visualise the movement of the animals, heatmaps were created for each version of the enclosure. Heatmaps were created for enclosures that were active for more than 12 h. This was done to exclude "intermediary" enclosures, where only one side of the enclosure had been shifted. The number of times an animal broke out of the enclosure was recorded, as well as the length of each breakout. The length of each breakout was determined as the duration of time between the Fence Status of the collar changing from Normal to Escaped and back to Normal again, rounded to the nearest half minute. 2.4.2. Habituation to Virtual Fencing The animals' habituation to the virtual fence was investigated by recording the number of auditory warnings and electric impulses received by each animal. The cumulative warnings and impulses were calculated and assessed, as well as the length of warnings over time. Furthermore, the number of electric impulses divided by the number of warnings was calculated over time, and the correlation between warnings and electric impulses was calculated using Pearson's product-moment correlation (rp). 2.4.3. Herd Behaviour The presence of herd behaviour was investigated by calculating the Pearson's correlation (rp) between the number of warnings received by a given calf and any other calf in an 8 h period (00-08 h, 08-16 h and 16-00 h). This was calculated for every pairwise comparison of the 17 animals, resulting in 136 correlations. A sliding window analysis was performed by repeating this calculation for shorter intervals. The correlation was calculated in an 18 period window, denoting the amount of consecutive 8 h periods included in each sliding window position. 2.4.4. Sliding Window Correlation To account for possible temporal variations in correlations between the animals, a sliding window correlation was used. A sliding window correlation is a way to assess a time series of data in smaller overlapping segments at a time, thus allowing for analysis of a long time series while still capturing short-range temporal variations in the correlation. In practice, the time series is tested one "window" at a time with a certain window size. The window is then shifted one position and the test is run again. As an example, if a window size of four is selected, the test is first run on data from day 1-4, then day 2-5, day 3-6 and so on. The results of these tests are recorded at the first point in the window, denoted the "sliding window position". The size of the window is increased until the median p-value of all correlations is below 0.05, and this is the included result. This way, more than half of the correlations were significant. 2.4.5. Predicting the Individuals with the Most Interactions with the Fence To determine whether the animals with the most physical activity received the most warnings, Spearman's rank correlation (rs) was calculated between the summed activity of an animal for the entire period and the summed number of warnings and impulses received by the same animal. The Spearman's correlation (rs) was also calculated for the summed number of warnings against the summed number of impulses the animals had received. Furthermore, the Spearman's correlation (rs) was calculated between the summed number of warnings an individual had received and the same individuals mean correlation to all the other animals, with regard to the number of warnings received in 8-h periods. 3. Results 3.1. Effectiveness of Virtual Fencing The virtual fencing system effectively kept the animals within the periodically moving enclosure during the 89-day period of data collection. In total, the animals spent 99.74% of the period inside the enclosure. The created heatmaps also indicated that the animals respected the virtual boundaries and stayed within the enclosure . Over the course of the 89-day period, 19 breakout events were recorded. If multiple animals escaped at the same time, this was counted as one event per escaped animal. The median escape time was 2 min and the most number of breakouts by an animal was three, with 12 of the 17 calves breaking out of the enclosure at least once . 3.2. Habituation to Virtual Fencing There was a noticeable variation in the number of warnings received by the animals. The lowest total number of warnings received by a calf was 237 (an average of 2.66 warnings per day), while the highest number received was 1874 (an average of 21.06 warnings per day). The frequency of warnings received by the animals seemed to decrease from late August . As with the number of warnings, the number of impulses received also varied between individuals. The lowest total number of impulses received by a single calf was 36 (an average of 0.40 impulses per day), while the highest number received was 181 (an average of 2.03 impulses per day). It is worth noting that for all calves, the frequency of impulses was highest at the start of the period and stagnated towards the end of the data collection period . During the the start of the experiment, the warning duration ranged from approximately 0.01 s to 65 s, with a wide spread and many outliers. Within the first couple of weeks, the spread reduced, as well as the median warning duration, which settled around 8-10 s . The median number of impulses an animal received per warning in the beginning was approximately 0.5, but immediately trended downwards before reaching a median of 0 in late August . The correlation between the number of daily warnings and impulses an animal received throughout the period showed considerable variation, with the weakest correlation being rp=0.43 (ID: 90754) and the strongest being rp=0.85 (ID: 89495). 3.3. Herd Behaviour The results of the correlation and sliding window correlation tests run in regards to analysing herd behaviour were inconclusive and have therefore been moved to Appendix C. 3.4. Predicting the Number of Warnings for Each Animal A moderate positive correlation between the summed activity and summed number of warnings an animal received throughout the data collection period was observed (rs=0.56, p<0.05). No correlation between summed activity and summed impulses was found. Equally, no significant correlation was found between the summed number of warnings a bull calf had received and the mean correlation between the number of warnings received by the same calf and all other calves. 4. Discussion 4.1. Effectiveness of Virtual Fencing Throughout the 89-day period, the virtual fence successfully kept the 17 calves inside the virtual enclosure zone 99.74% of the time, even with daily changes in the virtual boundary. This supports Hypothesis (1), which states that the system will contain the animals more than 99% of the time. This is comparable to another study, where 12 dairy cows were kept within a 0.83 hectare enclosure for 99% of the time in a six day period . The positional data of the calves clearly showed that they respected the virtual boundary (Appendix B). The calves spent most of their time near the sheltering facilities and the water trough located in the northwest of the enclosure. Moreover, the calves grazed close to the virtual boundary to the east, where fresh grass was available (Appendix B). The fact that the calves clearly respected the virtual boundary despite the higher feed availability outside the boundary corresponds with results from other studies where virtual fencing kept cattle away from feed attractants . A total of 19 breakouts were recorded between 12 of the animals; however, the fact that the median time before an escaped animal returned to the enclosure was just 2 min could indicate that the breakouts were not deliberate attempts to escape . The remaining five animals did not escape at all. According to the farmer, the calves would sometimes push each other outside the virtual boundary, which could explain some of the breakouts. The ease with which the animals were able to re-enter the enclosure after a breakout, due to the lack of a physical barrier, meant that the farmer did not have to shoo the escaped animals back into the enclosure. The gregarious nature of the bull calves could also explain the short time between an escape and the animal re-entering the enclosure, as they would seek to return to the herd . The five animals that did not escape the enclosure throughout the entire experiment were also the animals that had received the fewest number number of impulses . This could be an indication that these animals were less prone to be pushed around by their herdmates, or were simply less inquisitive regarding the enclosure border. 4.2. Habituation to Virtual Fencing The frequency of warnings and impulses received by the animals reduced over time, with the number being notably lower in September than in July . This indicates that the bull calves needed fewer warnings to learn where the virtual boundary was placed, despite the fact that it was shifted at regular intervals. However, in line with several other studies, the amount of warnings and impulses received varied considerably between individuals . Equally, the Pearson's correlation between the number of daily warnings and impulses received varied between individuals (Section 3.2). This variation could be an expression of different personalities among the bull calves or the hierarchical structure of the herd. Some calves continued to receive a relatively high number of warnings, albeit at a lower frequency, while others barely received any warnings in the latter half of the data collection period. This could indicate that those receiving many warnings are "testers" that determine where the new virtual boundary is placed for the rest of the herd. However, this hypothesis is not immediately supported by the observation that, throughout the data collection period, the correlation between the number of warnings received by any two calves was positive for all pair-wise comparisons . If negative correlations had been observed, this would clearly indicate that when these "testers" received warnings, the rest of the herd would actively avoid warnings. However, even if some animals tried to avoid warnings because they observed others interact with the virtual boundary, this would likely be masked by the gregarious nature of cattle. As such, even if they actively tried to avoid warnings by observing others, they would still receive more warnings whenever the herd moved closer to the virtual boundary, making positive correlations very likely, especially due to the narrowness of the virtual enclosure. Despite the inter-individual differences, it is clear that the bull calves became habituated to the virtual fencing system. As such, the amount of impulses compared to warnings decreased over time, which supports Hypothesis (2) . This hypothesis states that the animals would receive fewer impulses per warning over time. This indicates that the animals were increasingly able to react to the auditory warnings to avoid receiving an electric impulse. The median amount of impulses per warning even reached zero in late August. This is positive, as it clearly shows that the bull calves learnt to associate the warnings with impulses, and reacted favourably when receiving warnings. Another study indicated that increased stress does not occur among cows managed with virtual fencing . The decreasing trend in impulses per warning is in line with other studies, which found that the number of warnings and total impulses decreased significantly over time . The decrease in the median length of warnings supports the notion that the calves became habituated to the system and reacted to the warnings, turning away from the virtual boundary before receiving an impulse . The warning duration stabilised after a few weeks, which could mean the animals became so familiar with the system that they learnt how long they could safely wait before turning away from the virtual boundary without receiving an impulse. 4.3. Herd Behaviour As a new way of analysing temporal data gathered from animals, such as from these calves, a sliding window correlation was run on the number of warnings any two calves had received in subsequent 8 h periods. A sliding window correlation makes it possible to capture any variations or trends in time, rather than relying on a single result independent of time. In this study, it was decided that due to the large window size of 8 h, the results would be too inaccurate and any discussion of these too speculative. Therefore, the results are only included in Appendix C. The authors of this paper suggest that future studies should continue to explore the use of sliding window correlations and other sliding window analyses to better capture temporal changes and trends. 4.4. Predicting the Number of Warnings for Each Animal A moderate correlation between summed activity and summed number of warnings received was found (Section 3.4). This supports Hypothesis (4), that animals with higher activity receive more warnings. Animals that are more active tend to encounter the virtual fence more frequently than those that are more sedentary. This was expected, as an animal has to be moving to receive a warning. The fact that the correlation was only moderate may be explained by other confounders, such as risk tolerance, foraging and herd behaviour. However, no correlation was found between summed activity and summed number of impulses, indicating that overall activity is not a contributing factor in receiving more impulses (Section 3.4). This does not support our Hypothesis (4), that the most active calves receive the most impulses. Interestingly, the correlation between summed warning and activity and the lack of correlation between impulses and activity indicate that animals that move around more do not receive more impulses than more sedentary animals, despite receiving more warnings. It is possible that the more active animals are better at reacting to the warnings, as they receive them more frequently. It could also simply be that all the animals had learnt to avoid impulses, such that only the number of warnings was affected by the activity of the animal. Further research is required to ascertain which statement is most likely. Lastly, a moderate correlation between summed number of warnings and summed number of impulses was found, which was to be expected, as an animal cannot receive an impulse without first receiving a warning. The correlation is not strong because the animals can receive warnings without impulses. The correlation does support the notion that the animals are learning to react to the warnings when the lack of correlation between activity and impulses is taken into account. A correlation between warnings and impulses would indicate that more active animals receive more impulses due to receiving more warnings, but, as discussed, that is not the case. 5. Conclusions In conclusion, the Nofence(c) virtual fencing system was capable of keeping the bull calves in a holistically managed enclosure for more than 99% of the time, and the calves that escaped returned of their own accord after a short time. The bull calves became habituated to the virtual fencing system, receiving fewer warnings and impulses over time. Additionally, they learnt to respond favourably to auditory warnings, receiving fewer impulses compared to warnings over time, reaching a median of zero impulses per warning for the last month of the data collection period. The median warning length decreased at the beginning of the period but then stabilised, indicating that the calves became so used to the system that they did not react to warnings immediately, but had figured out when to turn away from the boundary to avoid impulses. A sliding window correlation was used to test for short range changes or temporal trends in the median correlation between the number of warnings received by any two calves, but the results were inconclusive. Some short-range fluctuations were shown using the analysis, showcasing a need for future studies to take temporal variations into account when analysing these types of data. The calves with the highest physical activity received the most warnings, but no other significant results were found when trying to predict which animals would receive the most warnings. Acknowledgments Special thanks to Dan Pode Poulsen and Michael Baun for providing data, consulting, continuously sharing information and for letting us carry out the experiment as part of the ongoing project of testing Nofence(c) virtual fencing on the Danish island of Fano. This project was conducted by a partnership consisting of landowner Dan Pode Poulsen, farmer Michael Baun, The Wadden Sea National Park, The Municipality of Fano and Hedeselskabet. Author Contributions Conceptualisation, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S., A.E.N., A.K.O.A., D.B., A.C.L., C.S., J.F. and C.P.; methodology, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S., A.E.N., A.K.O.A., D.B. and C.P.; formal analysis, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S. and A.E.N.; investigation, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S. and A.E.N.; data curation, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S. and A.E.N.; writing--original draft preparation, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S. and A.E.N.; writing--review and editing, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S., A.E.N., A.K.O.A., D.B., A.C.L., C.S., J.F. and C.P.; visualisation, S.K.S., M.F.A., J.N.S.J., I.Z., E.B.S. and A.E.N.; supervision, A.K.O.A., D.B., A.C.L., C.S., J.F. and C.P. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was conducted according to the institutional guidelines for animal research (directive 2010/63/EU), and approved by the Animal Experiments Inspectorate of Denmark (2020-15-0201-00588, approval date: 8 July 2020) prior to the start of the study. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available on request from the corresponding author. Conflicts of Interest The authors declare no conflict of interest. Appendix A. Maps of Virtual Enclosures Figure A1 Virtual enclosure version 1 dating from 4 July to 10 July. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A2 Virtual enclosure version 2 dating from 10 July to 18 July. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A3 Virtual enclosure version 3 dating from 18 July to 26 July. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A4 Virtual enclosure version 4 dating from 26 July to 3 August. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg'53.531'' N. Map data from OpenStreetMaps Figure A5 Virtual enclosure version 5 dating from 4 August to 11 August. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A6 Virtual enclosure version 6 dating from 11 August to 19 August. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A7 Virtual enclosure version 7 dating from 19 August to 27 August. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A8 Virtual enclosure version 8 dating from 27 August to 8 September. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Map data from OpenStreetMaps Figure A9 Virtual enclosure version 9 dating from 8 September to 25 September. The dashed black line represents the physical fence surrounding the 8.2 ha grazing area. The marked green area represents the virtual enclosure. Only virtual enclosures active for more than 12 h were included. The coordinates of the upper left corner of the map frame are 55deg25'23.131''E 8deg23'53.531''N. Map data from OpenStreetMaps Appendix B. Heatmaps of Cattle Movement in Virtual Enclosures Figure A10 Heatmap series 1 visualising all Poll messages sent during the period from 4 July to 10 July. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'3.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A11 Heatmap series 2 visualising all Poll messages sent during the period from 10 July to 18 July. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A12 Heatmap series 3 visualising all Poll messages sent during the period from 18 July to 26 July. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A13 Heatmap series 4 visualising all Poll messages sent during the period from 26 July to 3 August. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A14 Heatmap series 5 visualising all Poll messages sent during the period from 3 August to 11 August. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A15 Heatmap series 6 visualising all Poll messages sent during the period from 11 August to 19 August. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A16 Heatmap series 7 visualising all Poll messages sent during the period from 19 August to 27 August. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A17 Heatmap series 8 visualising all Poll messages sent during the period from 27 August to 8 September. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure A18 Heatmap series 9 visualising all Poll messages sent during the period from 8 September to 25 September. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour indicates the number of Poll messages within a 10 m radius. The brightest colour represents the areas with the lowest density of Poll messages, while the darkest colour represents the areas with 250 or more Poll messages within the radius. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Appendix C. Herd Behaviour Appendix C.1. Results of Herd Behaviour There was a positive correlation between the number of warnings received by each individual animal and all the other animals. The positive correlation indicated that one bull calf receiving an auditory warning would to some degree lead to another bull calf also receiving an auditory warning . There was notable variation in the correlation coefficients, with results ranging from 0.13<=rp<=0.6. Figure A19 Pearson's correlation coefficients of the pairwise number of warnings received by the bull calves. The colour ramp indicates the degree of correlation from white (0) to blue (1) with a darker blue indicating a stronger correlation. Correlation coefficients are only shown for significant results. The numbers around the edge of the matrix are the ID numbers of the bull calves. The median correlation between the number of warnings received by two individual calves in 8 h periods showed some temporal fluctuations, but seemed to be more or less constant over time. A linear regression model showed a slight increase in the median correlation (Pearson's r =-0.4+5.13*10-4*(8 h period)). The overall regression was statistically significant (R2 = 0.11, F(1,247) = 30.85, p < 0.001). However, due to the low R-squared value, the regression did not offer sufficient prediction accuracy to be accepted. Polynomial regression did not offer any significant increase in the R-squared value (R2 = 0.12, F(2,246) = 17.3, p < 0.001). Appendix C.2. Discussion of Herd Behaviour A positive Pearson's correlation between the amount of warnings received was found for every calf pair bar one . This supports Hypothesis (3), which states that there would be a positive correlation between the number of warnings received by two random calves in 8-h periods. The positive correlations indicate that the animals in question were more likely to receive a higher number of warnings in time periods where their herd mates received numerous warnings. This suggests that they exhibit herd behavior, which has also been documented by Hubbard et al. . If a negative correlation between the number of warnings received between two calves had been observed, it would mean that the animals were less likely to receive a warning whenever another calf had received a warning. Interestingly, the pairwise correlations varied considerably . One possible explanation for this variation could be the hierarchical structure of the herd, with any given calf mostly moving in close proximity to specific herd mates. However, a review of the existing literature on social dominance in beef cattle by Hubbard et al. found little to no evidence for herd movement being related to social dominance rank. It is not possible to tell with certainty whether a positive correlation means the calves actually follow each other, as the test was performed using long time periods of 8 h. A shorter time period might provide a clearer picture. Another explanation could be that the less correlated calf is relatively less interested in performing the same activity as the herd. It may be more likely to rest or graze at different times compared to the other animals. As all the correlations are still positive, it would, of course, still rest and graze mostly at the same time, but it is possible that it is less affected by the actions of the herd. This could also indicate a specific position in the hierarchy, or it could be down to the personality of the animal. As a new way of analysing temporal data gathered from animals, such as from these calves, a sliding window correlation was run on the number of warnings any two calves had received in subsequent 8-h periods. A sliding window correlation makes it possible to capture any variations or trends in time, rather than relying on a single result independent of time. In our study, the median correlation between the number of warnings received by two animals did not change significantly over time using a sliding window correlation . Despite that there were no significant trends in the median correlation over time, the median correlation did seem to fluctuate noticeably, indicating that a simple correlation could prevent researchers from getting the full picture when analysing temporal data. A likely explanation for these fluctuations could be the decision to sum the warnings in 8-h periods and not split the sliding window correlation into three, such that all periods from the same day were tested against each other. Additionally, it could be hypothesized that the 8-h periods themselves were too large to capture short time variations. When performing a sliding window correlation, one has to consider the trade-off between the size of the window and the significance of the results. A smaller window allows for higher fidelity, with larger windows smoothing out possible changes or fluctuations. In this study, it was decided to use the smallest window size, which gave a median significance value of less than 0.05, to ensure that more than half of the correlations run were significant. However, one might argue that the window should have been even larger to increase the predictive accuracy. Future studies should continue to explore the use of sliding window correlations and other sliding window analyses to better capture temporal changes and trends. Figure A20 Median sliding window correlation of the number of 8 hourly warnings between individuals over time with a window of 18 periods. The blue line is the result of linear regression (Pearson's r =-0.4+5.13*10-4*(8 h period)). Vertical dotted grey lines show the start time of each version of the virtual enclosure. Figure 1 The island of Fano located in the Wadden Sea of Denmark. The dashed black line represents the physical fence surrounding the 8.2 ha pasture. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. This dataset includes Intellectual Property from European National Mapping and Cadastral Authorities and is licensed on behalf of these by EuroGeographics. Original dataset is available for free at Terms of the licence available at All attribution statements can be found here. Figure 2 Heatmap visualising all Poll messages sent during the period from 25 September to 3 October. The green area shows the virtual enclosure area to which the bull calves were limited. The white to red colour scale indicates the number of Poll messages within a 10 m radius on a discrete scale, ranging from 1 point to above 250 points. The coordinates of the upper left corner of the map frame are 55deg25'23.131'' E 8deg23'53.531'' N. Contains data from the Agency for Data Supply and Infrastructure, Forarsbilleder Ortofoto-GeoDanmark, December 2022. Figure 3 Boxplot of the duration of time spent outside the virtual enclosure for each breakout event during the 89-day period. The points represent each breakout and the colours indicate the escaped individual's ID number. The boxplot shows min, Q1, median, Q3 and max. Outliers are calculated as 1.5 times IQR. The points are mainly clustered between 0 and 2 min with a few breakouts ranging from 13 to 33.5 min and a single breakout being an outlier at 66 min. Figure 4 Cumulative number of warnings received by each bull calf between 4 July 2022 and 30 September 2022. The ID Number refers to each of the 17 calves. Figure 5 Cumulative number of impulses received by each bull calf between 4 July 2022 and 30 September 2022. The ID Number refers to each of the 17 calves. Figure 6 Warning duration in seconds over time for all animals represented as a series of boxplots showing min, Q1, median, Q3 and max. Outliers calculated as 1.5 times IQR. Figure 7 Number of impulses per warning over time. Ratio shown as boxplots showing min, Q1, median, Q2 and max. Outliers calculated as 1.5 times IQR. animals-13-00917-t001_Table 1 Table 1 Overview of the different message types and description of frequency, data type and number of observations. Type Frequency Data Type No. of Obs. Poll Every 15 min Positional 151,576 Seq Every 30 min Activity 71,990 Warning After receiving warning Positional 13,906 Status Upon status change (see Table 2) Status 2153 Zap Upon receiving impulse Positional 1538 animals-13-00917-t002_Table 2 Table 2 Overview and description of the different fence statuses. Fence Status Description Normal The virtual enclosure is active Not Started The virtual enclosure is not active Maybe Out Of Fence The collar position is outside the enclosure, but the GPS accuracy is not adequate to a trigger warning Escaped The animal has escaped the enclosure Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000216 | The aim of this study was to evaluate the clinical outcomes of a large series of brain metastatic renal cell carcinoma (BMRCC) patients treated in three Italian centers. Methods: A total of 120 BMRCC patients with a total of 176 lesions treated were evaluated. Patients received surgery plus postoperative HSRS, single-fraction SRS, or hypofractionated SRS (HSRS). Local control (LC), brain distant failure (BDF), overall survival (OS), toxicities, and prognostic factors were assessed. Results: The median follow-up time was 77 months (range 16-235 months). Surgery plus HSRS was performed in 23 (19.2%) cases, along with SRS in 82 (68.3%) and HSRS in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy. The main total dose and fractionation used were 20-24 Gy in single fraction or 32-30 Gy in 4-5 daily fractions. Median LC time and 6 month and 1, 2 and 3 year LC rates were nr, 100%, 95.7% +- 1.8%, 93.4% +- 2.4%, and 93.4% +- 2.4%. Median BDF time and 6 month and 1, 2 and 3 year BDF rates were n.r., 11.9% +- 3.1%, 25.1% +- 4.5%, 38.7% +- 5.5%, and 44.4% +- 6.3%, respectively. Median OS time and 6 month and 1, 2 and 3 year OS rates were 16 months (95% CI: 12-22), 80% +- 3.6%, 58.3% +- 4.5%, 30.9% +- 4.3%, and 16.9% +- 3.6, respectively. No severe neurological toxicities occurred. Patients with a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, absence of EC metastases, and a combined local treatment (surgery plus adjuvant HSRS) had a better outcome. Conclusions: SRS/HSRS is proven to be an effective local treatment for BMRCC. A careful evaluation of prognostic factors is a valid step to manage the optimal therapeutic strategy for BMRCC patients. brain metastases renal cell carcinoma radiosurgery hypofractionated radiosurgery surgery This research received no external funding. pmc1. Introduction The increasing incidence of renal cell carcinoma (RCC) and the prolonged survival associated with development of more effective systemic therapies have led to a greater observation of metastatic spread, most commonly into lung, liver, or bone . Brain metastasis (BM) is a more infrequent event, ranging from 2% to 15%, occurring late during the disease course, and usually accompanied by a diffuse extracranial metastatic involvement . Notwithstanding the metastatic disease status, the outcome of extracranial metastatic RCC patients remains satisfactory with about 50% survival after 5 years, unlike the brain metastastic disease patients, characterized by a worse prognosis with an median overall survival (OS) time that does not exceed 10 months . The presence of BMs represents an exclusion criterion in a large part of randomized prospective trials due to the poor local control (LC) in employing systemic treatment and the poor outcome of these patients . Indeed, most of the available data come from retrospective observation, reflecting the difficulty in drawing any conclusions concerning the management of these patients. Currently, brain metastatic RCC (BMRCC) patients should receive brain-directed local therapy with radiation therapy and/or surgery, as suggested by international guidelines, considering the limited intracranial efficacy of the current systemic therapy agents . Surgical resection followed by adjuvant radiosurgery in single (SRS) or multiple fractions (HSRS) on the tumor bed is indicated in selected patients with single and large BMs, a good KPS, and limited systemic disease. Results of randomized trials showed a local control in site of treatment greater than 80% with improvement in neurocognitive functions . For patients with small and/or multiple BMs, or who are unsuitable for surgery, SRS or HSRS is able to provide excellent local control with negligible toxicity . Unfortunately, in studies leading to the current standard of care for brain metastatic patients, a small number (4-17%) of the included patients had a primary diagnosis of RCC, and, to date, there has been no prospective study analyzing the outcome of this subgroup. However, considering the availability of more effective systemic therapy able to obtain a better extracranial disease control, as well as the most common application of brain MRI to detect small brain lesions, an increase in BMRCC patients is expected in the next few years. Given the paucity of data in this setting, this is an important area for further research, and treating patients with mRCC harboring BMs remains a challenge. On the basis of this background, we evaluated the outcome of a large series of BMRCC patients treated in three Italian Institutions aiming to evaluate efficacy of local treatments (SRS/HSRS with or without surgery), and to identify prognostic factors eventually conditioning outcome. 2. Material and Methods 2.1. Patients and Procedures The present study includes patients with limited BMs (up to four) from RCC treated with single-dose SRS or HSRS (3-5 fractions) in relation to the number and cumulative tumor volume of the brain lesions. Single-dose SRS was employed in cases of small lesions (<=3 cm) or multiple BMs with a cumulative tumor volume up to 15 cm3; HSRS was administered for large BMs (>3 cm) unsuitable for surgical resection in relation to patient age, performance status, and diffuse and uncontrolled extracranial metastases. Surgical resection followed by SRS/HSRS was performed in select cases characterized by KPS 90-100, controlled extracranial disease, single BM with maximum diameter >=21 mm, presence of two BMs in which one was larger and conditioning a mass effect, life expectancy longer than 3 months, and progressive neurological deficits or seizures. All patients were treated in agreement with the Helsinki declaration. This study was based on a retrospective analysis of treatment charts and received approval by the local Ethics Committee. 2.2. Treatment: SRS/HSRS For target volume delineation, contrast-enhanced T1MRI and CT scans were acquired, and images were co-registered. For patient immobilization and repositioning, a frameless system was employed. The gross target volume (GTV) corresponded to the BM volume; the planning target volume (PTV) was generated by adding isotropic margins from GTV of 0-3 mm. The delineated organs at risk (OARs) were the brain, brainstem, optic nerves, chiasm, and lenses. The total doses and fractionation planned according to the maximum diameter of BMs were 24 Gy/1 fraction for lesions up to 2 cm, 20 Gy/1 fraction for lesions up to 2-3 cm, 32 Gy/4 fractions for BMs 3.1-5 cm, and 30 Gy/5 fraction for larger ones; following surgical resection, a dose of 30 Gy in three fractions on the tumor bed was administered. Patients were treated with the volumetric modulated arc technique RapidArc (LINAC or Cyber Knife); Exactrac (Brainlab) and/or cone beam CT imaging was performed daily for patient setup and positioning verification. 2.3. Systemic Therapy Some patients received systemic adjuvant therapy after local treatments of BMs. Different regimens were used in relation to previous treatments received, consisting of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or immune checkpoint inhibitors (ICIs) according to national and international guidelines. 2.4. Outcome Evaluation Clinical outcome was evaluated by neurological examination and brain MRI performed 2 months after RT and every 3 months thereafter. Local progression was defined as a radiographic increase in enhancing abnormalities in the irradiated volume on serial MR imaging according to RANO criteria, and BDF was defined as the presence of new BMs or leptomeningeal enhancement outside the irradiated volume . Toxicities were assessed during treatment at 2 months after RT and every 3 months thereafter, and then graded according to Common Terminology Criteria for Adverse Events version 4.0. Systemic disease was evaluated by contrast-enhanced total body CT scan and 18-FDG CT-PET. 2.5. Statistical Analysis Standard descriptive statistics were used to describe the general data behavior. Survival and recurrence time observations were computed according to the method of Kaplan and Meier, starting from the date of BM treatments. In order to investigate the prognostic role of different individual variables, the log rank test and univariate Cox regression were used, respectively, for categorical and numerical variables age, gender, KPS, stage at diagnosis, grade of primary tumor, interval time between primary tumor diagnoses and appearance of brain metastases, RCC-specific GPA score, IMDC score, presence of other metastatic site at time of BMs, number, site and size of BMs, type of local treatment performed, and systemic treatment administration. The multivariate Cox model was used as a method to estimate the independent association of a variable set with local control (LC), brain distant progression (BDF), progression-free survival (PFS), and overall survival (OS). Statistical analysis was performed using Medcalc software, v17.7 (MedCalc software, Ostend, Belgium). 3. Results 3.1. Patients and Treatments From April 2003 to July 2021, among 136 BMRCC patients treated, 120 were evaluable and, therefore, included in the present analysis. Eighty-eight (73.3%) were male and 32 (26.7%) were female. Patient, tumor, and treatment characteristics at diagnosis are shown in Table 1. Upon BM occurrence, a large number of patients had a good KPS (73.3%), presence of extracranial metastases (89.2%), an RCC-specific GPA (graded prognostic assessment) score 3.5-4 (47.5%), and an intermediate International Metastatic Database Consortium (IMDC) score (73.3%). The median interval time (IT) between the diagnosis of primary RCC and the appearance of BMs was 28 months (range 0-253 months); the total number of BMs irradiated was 176, and most patients had 1-2 BMs (91.7%). The treatments performed were surgical resection followed by SRS/HSRS on the tumor bed in 23 (19.2%) cases, SRS alone in 82 (68.3%), and HSRS only in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy after BM treatment consisting of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and/or immune checkpoint inhibitors (ICIs). The most frequent drugs employed were pazopanib, cabozantinib, sunitinib nivolumab, and ibilimumab. Details are shown in Table 2. Local control (LC), distant brain failure (BDF), progression-free survival (PFS), and overall survival (OS) analysis The median follow-up time from BM treatment was 77 months (range 16-235 months). Seven (5.8%) patients had local recurrence at the site of treatment at a median time of 9 months (range 7-16 months). The median LC time and 6 month and 1, 2, and 3 year LC rates were nr, 100%, 95.7% +- 1.8%, 93.4% +- 2.4%, and 93.4% +- 2.4%, respectively as shown in Figure 1. Brain distant failure (BDF) occurred in 35 (29.2%) patients at a median time of 10 months (range 1-113 months). The median BDF time and 6 month and 1, 2, and 3 year BDF rates were n.r., 11.9% +- 3.1%, 25.1% +- 4.5%, 38.7% +- 5.5%, and 44.4% +- 6.3%, respectively. The median PFS time and 6 month and 1, 2, and 3 year PFS rates were 5 months (95% CI: 4-8), 50% +- 4.5%, 30% +- 4.1%, 9.9% +- 2.8%, and 4.1% +- 2.1%, respectively. The median OS time and 6 month and 1, 2, and 3 year OS rates were 16 months (95% CI: 12-22), 80% +- 3.6%, 58.3% +- 4.5%, 30.9% +- 4.3%, and 16.9% +- 3.6%, respectively. At the last observation time, 17 (14.2%) patients were alive, and 103 (85.8%) were dead, three (2.9%) from intracranial progression, 90 (87.4%) from extracranial progression, eight (7.8%) from extracranial and brain progression, and two (1.9%) from a tumor-unrelated cause. Figure 2 shows the BDF, PFS, and OS for all patients treated. 3.2. Prognostic Factors Analysis Prognostic factors conditioning LC, BDF, PFS, and OS were analyzed. Gender, age, and stage at diagnosis were not recorded as the conditioning outcomes. LC was significantly influenced by the type of local treatment performed; in particular, patients receiving surgical resection followed by adjuvant HSRS had 6 month and 1, 2, and 3 year LC rates at treatment site of 100%, 100%, 96.2% +- 6.7%, and 96.2% +- 6.7 compared to 100%, 97.2% +- 1.9%, 95.2% +- 2.7%, and 95.2% +- 2.7% for SRS alone, and 100%, 80.8% +- 10.3%, 80.8% +- 10.3%, and 80.8% +- 10.3% for HSRS alone, respectively (p = 0.0258). No statistically significant factors were identified as impacting BDF. Patients harboring a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, and an absence of EC metastases, who received a combined local treatment (surgery plus adjuvant HSRS), had a better outcome. Among these patients, the administration of systemic treatment, particularly ICIs, influenced survival. Details about prognostic factors statistically relevant for PFS and OS are shown in Table 3. 3.3. Salvage Treatment for Intracranial/Local Progression Among seven local relapse patients, all received further treatments, consisting of surgery followed by adjuvant HSRS in two cases, HSRS in four cases, and SRS in one case. In almost all patients with BDP (32/35), a new local treatment was performed: 26 SRS, two HSRS, and four WBRT. 3.4. Toxicity Treatment-related toxicities occurred in 23 (19.2%) patients and consisted of nausea, vomit, and headache in six (5%), partial or generalized seizure in seven (6%), motor deficit in four (3.3%), and grade 2-3 radionecrosis in six (5%) patients. 4. Discussion The results of a retrospective multi-institution study assessing the role of local treatments in brain metastatic renal cell carcinoma (BMRCC) patients were provided. A total of 120 patients with 176 BMs treated were evaluated. SRS or HSRS alone was performed in 80% of patients, while 20% received surgical resection followed by SRS/HSRS on the tumor bed. Although RCC is considered a radioresistent tumor, the administration of SRS or HSRS, which enables the delivery of ablative RT doses in one or few fractions, led to satisfactory local control. Indeed, the 1 and 3 year LC rates were 96% and 93%, respectively, with only 7/176 (~4%) cases of relapse at the site of treatment. Our results are comparable to or better than published series . Wardak et al. analyzed 38 patients treated with radiosurgery on 243 brain metastases . The reported 1 and 2 year local control rates were 92% and 86%, respectively. Similarly, Klausner et al. treated 362 consecutive patients with single-dose SRS on brain metastases, using Gammaknife and Linac-based SRS mode . The 1 and 3 year LC rates were 94% and 92%, respectively; significant predictive factors were a minimal dose >17 Gy and concomitant TKI treatment, administered in about one-third of the patients. In our series, single-dose SRS using a median dose of 24 Gy proved to be more effective compared to the hypofractionated schedule employing a median dose of 30 Gy in five fractions, although these data may have been affected by the different volume of BMs treated (larger in the HSRS). A more beneficial effect on LC was recorded using a combined treatment (surgery plus HSRS on the tumor bed), obtaining a durable LC in almost all patients treated (96%). Nonetheless, accurate patient selection is essential to plan the optimal local approach, particularly when surgical resection is being considered. Several scores exist to predict survival . They involve some clinical features (KPS, age, extracranial metastatic spread, and interval time between initial RCC diagnosis and BM occurrence) and some BM characteristics (number of BMs, and cumulative intracranial tumor volume) associated with outcome. Patients with a single or limited BMs, controlled or limited systemic cancer, and active EC metastases suitable for local treatments would seem to be adequate candidates for a combined local treatment consisting of surgery followed by radiation therapy. In addition, although the patient's neurological status can represent a critical parameter for survival, surgical resection can lead to relief of neurological symptoms by improving patient QoL. In our series, surgery was performed only in patients with single BM, good KPS, and absence or limited/controlled EC metastases. However, considering the results obtained, a wider patient selection criteria could be advisable, including patients with limited BMs (up to four) in which SRS might be administered on the other lesions before surgery, as well as patients suitable for surgery or SBRT on the EC metastatic site, or patients in which a systemic therapy could be performed, aiming to optimally control the whole disease. Survival was also highly satisfactory, with 1, 2, and 3 year OS rates of 58%, 31%, and 17%, respectively. In other published papers, the occurrence of BMs compared to EC was recorded as negatively influencing survival. Zaorsky et al., in their meta-analysis, showed a 1 year survival rate of 87% for extracranial metastatic patients, in contrast to 50% in cases of intracranial disease . This better outcome could be related to a greater benefit observed when employing systemic therapy, which is less effective to control brain disease. Published series, assessing the role of systemic therapy rather than local treatment in BMRCC patients, failed to prove a clear beneficial effect on outcome. A phase II trial investigated the efficacy of sunitinib in 16 BMRCC patients ineligible for local treatment and naive to prior systemic therapy, showing no beneficial effect on objective response, median time to progression, and median OS . Similarly, data available using sunitinib and pazopanib, sorafenib, or axitinib have not proven any efficacy in brain disease control or survival . More promising results have been recorded using cabozantinib, a TKI able to easily penetrate the BBB, as documented by preclinical models, retrospective analysis, and the preliminary results of the ongoing prospective phase II CABRAMET study (NCT03967522) . The benefits and safety of ICIs have also been investigated . The interim results of the ongoing CheckMate 920 study, aiming to assess the role of nivolumab plus ipilimumab in BMRCC patients, showed an ORR of 28.6%, and a median PFS of 9.0 months. The small sample size and the short follow-up time do not allow clearly concluding to the benefit of this treatment, but the preliminary results seem encouraging. The challenge is now to assess the optimal therapeutic approach, able to control both cranial and EC metastatic disease. The combination of TKIs and local therapy has the advantage of allowing a better control of systemic disease, and the possibility of carrying out the systemic treatment before the occurrence of BMs. On the other hand, the combination of RT and ICIs, through a complex immunologic synergic action, might also potentially improve the antitumoral response . Chen et al., in a retrospective trial, assessed the outcome of 260 brain metastatic patients with a broad spectrum of malignancies (including 33 BMRCCs) . Patients were treated with HFSRT/SRS alone, concurrent HFSRT/SRS + ICIs, or nonconcurrent HFSRT/SRS + ICIs. A significant improvement in OS and BDF was observed for concurrent HFSRT/SRS + ICIs compared to other groups, but no advantage in LC was determined. In our analysis, the administration of systemic therapy after local treatment (SRS/HSRS or surgery plus HSRS) showed a favorable effect on survival, with 3 year OS rates of 9% without treatment, 18% with TKIs, and 37% using ICIs (p = 0.0540). Our results confirm the need for a multimodal treatment approach. Indeed, patients receiving surgery plus SRS/HSRS and/or systemic therapy had better outcomes with more than one-third of patients alive at 3 years. In addition, patients without EC metastases at BM occurrence had a major advantage in terms of survival, reaching 44% at 3 years, suggesting that the control of all metastatic sites might improve the outcome of these patients with a poor prognosis. Unlike what is documented in the literature in our population, patients with an IT from primary diagnosis to occurrence of BMs shorter than 1 year had the better outcome. These data have to be interpreted with caution, and they appear difficult to explain. This finding might be related to a low disease burden in this group of patients and/or an early administration of systemic therapy. We are aware that our analyses have all the limitations of a retrospective study, including selected patients characterized by limited brain disease (up to four BMs), mainly 1-2 BMs, limited EC metastases, good KPS (90-100), intermediate IDMC score, and good RCC-GPA score, whereby surgery was possible in about 20% of cases, along with systemic therapy, TKIs or ICIs, administered in more than 60% of cases after local treatment. Notwithstanding, in our series, the main selection criterion for surgical resection was related to BM characteristics and extracranial disease status, and not exclusively to patients' general conditions. In spite of this, to our knowledge, this is one of the larger series published in the literature evaluating the role of local treatments in BMRCC patients, and the results obtained are highly satisfactory, paving the way for new prospective approaches in patients, until now, considered to have a poor prognosis. 5. Conclusions The presence of BMs in primary RCC patients define a metastatic disease with poor outcome. The control of brain disease is fundamental in allowing an acceptable QoL, to proceed with systemic therapy, potentially impacting survival. Our results underlined that SRS/HSRS is a safe and feasible treatment with satisfactory local control and negligible toxicity. A multimodal treatment approach including surgery, radiosurgery, and systemic therapy provided the best outcome. Further prospective studies are needed to identify patients in which a multimodal treatment approach can be considered. Author Contributions Conceptualization, P.N. and F.P.; methodology, G.D. and G.R.; software, F.L. and G.R.; validation, P.N., F.P., and C.F.; formal analysis, P.N., F.P., C.F., and G.R.; investigation, B.M., L.R., and L.B.; resources, G.M., E.C., and V.P.; data curation, P.N., G.M., and C.F.; writing--original draft preparation, P.N. and F.P.; writing--review and editing, P.N., M.B., F.P., C.F., G.M., V.P., L.F., and M.S.; visualization, C.F. and D.F.; supervision, M.S., L.F., F.P., and G.M.; project administration, C.F. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Humanitas Research Hospital (Rozzano) Milano, Italy. Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement Data supporting the reported results are available in the dataset generated by Humanitas Research hospital and can be provided if required. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Local control (LC) of brain metastases in patients with renal cell carcinoma treated with radiosurgery in single or multifraction (SRS/HSRS) or surgery followed by HSRS. Figure 2 Brain distant failure (a), progression-free survival (b), and overall survival (c) from brain metastasis treatments (radiosurgery or surgery followed by radiosurgery), in patients with primary renal cell carcinoma. cancers-15-01393-t001_Table 1 Table 1 Baseline patient, tumor, and treatment characteristics. No. pts Total (%) 120 100 Patient variables Median age years (range years) 60 (25-83) Gender Male 88 73.3 Female 32 26.7 KPS 70 2 1.7 80 30 25 90-100 88 73.3 Grade of RCC Grade 2 47 39.2 Grade 3 57 47.5 Grade 4 16 13.3 Stage at diagnosis I-III 71 59.2 IV 49 40.8 Extracranial metastases only 37 Brain metastases only 5 Extracranial + brain metastases 7 Treatments Surgery alone 81 67.5 S + Adjuvant systemic therapy 39 32.5 No. = number; pts = patients; BMs = brain metastases; KPS = Karnofsky performance scale; RCC = renal carcinoma cancer. cancers-15-01393-t002_Table 2 Table 2 Patient, tumor, and treatment characteristics at BM occurrence. No. pts Total (%) 120 100 Patient variables Median age years (range years) 64 (37-84) KPS 70 2 1.7 80 30 25 90-100 88 73.3 Median IT diagnosis/BM occurrence (range months) 28 (0-253) EC metastases at BM treatments No 13 10.8 Yes 107 89.2 No EC metastatic site 1 30 28 2 37 34.6 3 22 20.6 4 15 14 5 2 1.9 >5 1 0.9 RCC-specific GPA score 1.5-2 11 9.2 2.5-3 52 43.3 3.5-4 57 47.5 IMDC score Favorable 30 25 Intermediate 88 73.3 Poor 2 1.7 No BMs 1 84 70 2 26 21.7 3 8 6.6 4 2 1.7 BMs treatment SRS 1 fraction 82 68.3 Median dose Gy (range Gy) 24 (13-25) HSRS 3-5 fractions 15 12.5 Median dose Gy (range Gy) 30 (21-32) Surgery + adjuvant SRS/HSRS 23 19.2 Systemic treatment after RT Yes 77 64.2 ICIs 22 VEGFR TKIs 55 No 43 35.8 No. = number; pts = patients; BMs = brain metastases; KPS = Karnofsky performance scale; IT = interval time; EC = extracranial; RCC = renal carcinoma cancer; GPA = graded prognostic assessment; IMDC = International Metastatic Database Consortium; SRS = stereotactic radiosurgery; HSRS = hypofractionated radiosurgery; RT = radiation therapy; ICIs = immune checkpoint inhibitors; VEGFR TKI = vascular endothelial growth factor receptor tyrosine kinase inhibitors. cancers-15-01393-t003_Table 3 Table 3 Kaplan-Meier progression-free survival (PFS) and overall survival (OS) according to subgroup analyses from BM treatments. No Pts Median PFS Months (Months 95%CI) 6-Months PFS (SE) 1-Year PFS (SE) 2-Year PFS (SE) 3-Year PFS (SE) p Value Univariable HR Multivariable (95%CI) p Value Multivariable Progression free survival (PFS) 120 5 (4-8) 50 (+-4.5) 30 (+-4.1) 9.9 (+-2.8) 4.1 (+-2.1) KPS 70 80 90-100 2 30 88 1 (1-2) 8 (4-14) 5 (3-7) 0 56.7 (+-9.0) 48.9 (+-5.3) 0 36.7 (+-8.8) 28.4 (+-4.8) 0 0 13.9 (+-3.8) 0)0 0 5.8 (+-2.9) 0.0630 - nr IDMC score Favorable Intermediate Poor 30 88 2 8 (5-15) 4 (3-5) 1 68 (+-9.3) 39 (+-5.3) 0 40 (+-9.8) 20.7 (+-4.4) 0 20 (+-8.0) 4.4 (+-2.4) 0 8 (+-5.4) 2.2 (+-2.0) 0 0.0196 - nr EC met at BMs treatments No Yes 13 107 13 (2-24) 5 (4-7) 69.2 (+-12.8) 47.7 (+-4.8) 53.8 (+-13.8) 27.1 (+-4.3) 23.1 (+-11.7) 8.3 (+-2.7) 23.1 (+-11.7) 3.1 (+-1.7) 0.0500 - nr Treatments SRS/HSRS S+SRS/HSRS 97 23 5 (3-7) 17 (12-32) 41.2 (+-5) 87 (+-7) 20.6 (+-4.1) 69.6 (+-9.5) 2.0 (+-1.4) 47.8 (+-10.4) 1.0 (+-1.0) 19.9 (+-20.7) <0.0001 20.0376 (0.1629-0.4919) <0.0001 No Pts Median OS months (months 95%CI) 6-months OS (SE) 1-year OS (SE) 2-year OS (SE) 3-year OS (SE) p value univariable HR multivariable (95%CI) p value multivariable Overall Survival (OS) 120 16 (12-22) 80 (+-3.6) 58.3 (+-4.5) 30.9 (+-4.3) 16.9 (+-3.6) IT <=12 months >12 months 34 86 22 (16-30) 14 (10-17) 82.4 (+-6.5) 79.1 (+-4.3) 73.5 (+-7.5) 52.3 (+-5.3) 42.7 (+-9.0) 26.4 (+-4.7) 29.9 (+-8.8) 12.4 (+-3.7) 0.0251 - nr EC met at BMs occurrence No Yes 13 107 26 (15-37) 16 (11-19) 100 77.6 (+-4.0) 92.3 (+-7.3) 54.2 (+-4.8) 52.7 (+-14.1) 28.3 (+-4.4) 44 (+-14.3) 13.8 (+-3.5) 0.0498 - nr RCC specific-GPA score 1.5-2 2.5-3 3.5-4 11 52 57 17 (7-23) 10 (7-15) 22 (16-26) 90.9 (+-8.6) 67.3 (+-6.5) 89.5 (+-4.0) 63.6 (+-14.5) 42.3 (+-6.8) 71.9 (+-5.9) 9.0 (+-8.6) 24.3 (+-6.0) 41.4 (+-6.7) 9.0 (+-8.6) 8.8 (+-4.1) 26.7 (+-6.2) 0.0191 0.7170 (0.5393-0.9533) 0.0221 Treatments SRS/HSRS S+SRS/HSRS 97 23 14 (9-16) 26 (18-83) 75.3 (+-4.3) 100 50.5 (+-5.0) 91.3 (+-5.8) 24.2 (+-4.4) 59.1 (+-10.6) 12.9 (+-3.6) 34.5 (+-10.4) 0.0014 0.4038 (0.2285-0.7137) 0.0018 Systemic treatment after SRS/HSRS No VEGFR TKIs ICIs 43 55 22 16 (11-19) 16 (10-22) 28 (8-29) 79.1 (+-6.2) 80 (+-5.3) 81.8 (+-8.2) 60.5 (+-7.4) 56.4 (+-6.6) 59.1 (+-10.5) 23.3 (+-6.4) 30.1 (+-6.2) 51.7 (+-11.5) 9.3 (+-4.4) 17.7 (+-5.3) 36.9 (+-12.1) 0.0540 - nr ST + LT SRS/HSRS +TKIs S+SRS/HSRS+TKIsSRS/HSRS+ICIs S+SRS/HSRS+ICIs 48 7 16 6 16 (8-22) 23 (10-83) 12 (5-23) 29 (28-29) 77.1 (+-6.0) 100 75.0 (+-10.8) 100 54.2 (+-7.1) 71.4 (+-17.1) 43.8 (+-12.4) 100 28.2 (+-6.6) 42.9 (+-18.7) 32.8 (+-13.3) 100 16.5 (+-5.5) 28.6 (+-17.1) 32.8 (+-13.3) 50.0 (+-25.0) 0.0740 - nr No. = number; pts = patients; IDMC = International Metastatic Database Consortium; KPS=Karnofsky performance scale; EC met = extracranial metastases; BMs = brain metastases; SRS = stereotactic radiosurgery; HSRS = hypofractionated radiosurgery; IT = interval time; EC = extracranial; RCC = renal carcinoma cancer; GPA = graded prognostic assessment; S=surgery; ICIs = immune checkpoint inhibitors; VEGFR TKIs = vascular endothelial growth factor receptor tyrosine kinase inhibitors; ST = systemic treatment; LT = local treatment. 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PMC10000217 | Rapid urban development poses a threat to global biodiversity. At the same time, urban green spaces offer opportunities for holding biodiversity in cities. Among biological communities, the soil fauna plays a crucial role in ecological processes but is often ignored. Understanding the effects of environmental factors on soil fauna is critical for ecological conservation in urban areas. In this study, five typical green space habitats were selected including bamboo grove, forest, garden, grassland, and wasteland in spring, for detecting the relationship between habitats and Armadillidium vulgare population characteristics in Yancheng, China. Results indicate that soil water content, pH, soil organic matter, and soil total carbon varied significantly among habitats, as well as the body length and body weight of pill bugs. The higher proportion of larger pill bugs was found in the wasteland and the lower proportion in the grassland and the bamboo grove. The body length of pill bugs was positively related to pH. Soil total carbon, soil organic matter, and the number of plant species were correlated with the body weight of pill bugs. soil macrofauna land cover urban green space soil environment Innovation and Entrepreneurship Training Programs for College Students in Jiangsu Province202210324055Y This work was funded by the Innovation and Entrepreneurship Training Programs for College Students in Jiangsu Province (202210324055Y). pmc1. Introduction Urban environmental degradation threatens the sustainable development of the human society worldwide, and the degradation occurs not only in developed regions with a high level of urbanization, but also in developing regions with an accelerated urbanization process . Nowadays, the human society is undergoing the most rapid urbanization in history; many native habitats have been changed to be suitable for human living and have resulted in the homogenization of urban biomes . As an important component of urban ecosystems, urban green spaces make an important contribution to biodiversity in urban areas. Meanwhile, urban green spaces also play a vital role in creating recreation for residents and visitors. Soil fauna is an important ecological indicator for assessing urban soil quality and is involved in many soil functions . Macrofauna presents an extremely important function in ecosystems, participating in soil carbon transformation, sequestration, nutrient turnover, and maintenance of soil structure, and can be used to evaluate soil and ecosystem quality as well as to assess urban ecosystems . With the variations in soil physical, chemical, and microbial properties, the ecological environment of soil macrofauna has changed . Recently, a few studies have proved that the macrofaunal population characteristics are closely related to soil environments, the population characteristics vary among different habitats, and that population conditions can be used as indicators for soil environmental assessment . Armadillidium vulgare (Isopoda: Armadillidae), also known as the pill bug, is distributed worldwide, with particularly dense populations in temperate climates, and is one of the most important soil macrofauna in urban green spaces . The pill bug population thrives in moist climates and damp soils . Pill bugs are considered to be detritivores, eating decaying dead leaves and the remains of small invertebrates, and having important functions in soil fertility maintenance, plant nutrient supply, and soil purification, while also feeding on the fine roots and young leaves of plants . They recycle nutrients back into the ecosystem with important ecological significance . Different plant coverage may affect soil environments, such as soil moisture, soil nutrient status, pH, and so on . Therefore, we speculate that the population characteristics of pill bugs may relate to soil properties and vegetation types. For instance, soil organic matter is an important food source for pill bugs which may directly affect the distribution of pill bugs , which is influenced by land use, land cover, and anthropogenic random factors . However, we did not fully understand the relationship between the pill bugs' body parameters and soil properties. In this study, we investigated and analyzed the population characteristics of pill bugs among different green spaces on a university campus in Yancheng City, Jiangsu Province. This study aims to address the following two questions: (1) What is the variation pattern of soil properties and population characteristics of pill bugs among different habitats? (2) Which environmental factors can be used to explain the variation in pill bugs' population? 2. Materials and Methods 2.1. Study Area We conducted this study on Xinchang campus of Yancheng Teachers University (33.372~33.383deg N, 120.193~120.378deg E), Jiangsu Province, China . The climate type is region subtropical monsoon, and an average annual temperature of 13.7 degC and an average annual rainfall of 1051 mm was recorded. The campus area is 58.8 ha with a human population of about 12,000. The sampling work was conducted at the beginning of May 2022 in different habitats and finished in a week. 2.2. Habitat Selection and Soil Sample Collection On the campus, we selected five different habitats of green spaces with different land covers, including bamboo grove, forest, garden, grassland, and wasteland. The bamboo grove was dominated by pale bamboo (Phyllostachys nigra) with lush growth and partial leaf cover on the ground surface. The forest was mainly dominated by cherry (Prunus subg. Cerasus sp.), privet (Ligustrum lucidum), and golden raintree (Koelreuteria paniculata). Chinese violet cress (Orychophragmus violaceus) was the main vegetation in the garden. The grassland was mainly covered by mascarene grass (Zoysia tenuifolia), bermudagrass (Cynodon dactylon), and cogongrass (Imperata cylindrica). The wasteland has been unmanaged for about 8 years and has more plant species, including Chinese tallow tree (Sapium sebiferum), paper mulberry (Broussonetia papyrifera), sweet woodruff (Galium odoratum), etc. Five replicates of separate patches were used as sampling sites in each habitat, with a minimum distance of 2 m among the patches in the same habitat. All sampling sites were distributed in an area with a radius of 250 m. The compact distribution of the sampling sites was designed to reduce spatial variability. Details of the habitats are shown in Table 1. Representative green spaces were selected and randomly sampled, and 5 replicate sample plots (50 cm x 50 cm) were set in each habitat. In each plot, debris such as surface plant and animal residues were removed, and three soil cores (100 cm3, depth 5 cm) were taken by using a soil loop cutter. The soil cores were mixed and immediately packed in polyethylene plastic bags. The vegetation coverage and the number of plant species at each sampling site were recorded. The height of the highest plant was measured as the habitat description in each habitat. A total of 25 soil samples were collected from five habitats. 2.3. Determination of Soil Properties Part of the fresh soil samples was used for the determination of soil water content (WC) after oven-drying the samples at 105 degC for 24 h. Part of the fresh soil samples was sieved through an 8-mm sieve and air-dried at room temperature (about 20 degC) for three weeks. The air-dried soils were then sieved through a 2-mm sieve to remove coarse debris and stones. Afterward, the soil samples were used for the determination of electrical conductivity (EC), pH, available phosphorous (AP), and available nitrogen (AN). Then each of the prepared soil samples was ground and passed a 0.149-mm nylon sieve for determination of soil organic matter (SOM), total carbon (TC), and total nitrogen (TN) using the method introduced in the literature . In this research, the used facilities were listed as: a spectrophotometer (LTD. G-9, Nanjing Filer Instrument Co., Nanjing, China) for SOM, AP, and AN, a pH meter (FE 28, Mettler-Toledo Inc. Columbus, OH, USA) for pH, a conductivity meter (Mettler-Toledo FE28, Switzerland) for EC, and a Carbon Nitrogen Elemental Analyzer (Vario Macro Cube, Elementar Analysensysteme GmbH Inc., Langenselbold, Germany) for TC and TN. 2.4. Population Survey of Pill Bugs Pill bugs were captured by searching under fallen leaves, rocks, and topsoil in the selected habitats. They were then placed in bottles in the field and labeled, and were killed and kept by freezing at -20 degC in a refrigerator. Then, every individual was thawed and flattened for measurements of body length (l) on 1 mm x 1 mm grid paper, and the wet weight (m) by an electronic balance. 2.5. Statistical Analysis One-way analysis of variance (ANOVA) was conducted to analyze the soil properties and population characteristics of pill bugs in various habitats. Multiple comparisons were performed using Tukey's test or Dunnett's T3 test depending on whether they passed Levene's test for homogeneity . Principal components analysis (PCA) was performed on soil properties. The applicability of the data to PCA was tested by using the Kaiser-Meyer-Olkin (KMO) sampling adequacy (>=0.500) and Bartlett's test of sphericity (<=0.050) . The grouping composition of body length and body weight among different habitats was analyzed by using a Chi-square test, and the post-hoc testing was employed . The relationships between environmental factors and physical measurements of pill bugs were analyzed by using Cramer's V. Mantel test analysis . The relationship between body length and body weight of pill bugs was derived by using regression analysis. In this study, no variables were transformed. Significant statistical differences were used as p < 0.05. A map of sampling sites was created using ArcGIS 10.5 and statistical analyses were performed using Microsoft Office Excel 2021, SPSS18.0, R version 4.2.1, and PAST 4.03 software . 3. Results 3.1. Soil Properties and Vegetation Soil properties varied considerably among habitats (Table 2). The WC was highest in the forest at 20.54% and lowest in the grassland at 10.39% (F4,20 = 5.908, p < 0.01). The forest had the highest pH while the bamboo grove and the garden had the lowest (F4,20 = 8.317, p < 0.001). There were similar results for SOM (F4,20 = 9.587, p < 0.001), and TC (F4,20 = 8.427, p < 0.001), which had their highest values in the bamboo grove and the lowest values in the wasteland. There were significant differences in the number of plant species among habitats, with higher values in the forest and wasteland (F4,20 = 16.460, p < 0.001). The coverage in the bamboo grove, garden, and grassland was higher, while the coverage in the forest was the lowest (F4,20 = 95.667, p < 0.001). There were no significant differences in soil TN (F4,20 = 1.222, p > 0.05), AN (F4,20 = 1.458, p > 0.05), EC (F4,20 = 2.082, p > 0.05) and AP (F4,20 = 0.594, p > 0.05). The overall KMO value of 0.719 (>0.500) demonstrated the adequacy of sampling in this study. The sphericity of Bartlett's test for PCA showed that these approximately normal data for multiple variables were acceptable (kh2 = 62.736, df = 15, p < 0.001). Results of PCA showed that soil samples could be classified by habitat characteristics, and pc1 and pc2 could respond to 53.97% and 21.73% of habitat differences . SOM, TC, and vegetation coverage were positively correlated with pc1, whereas WC, pH, and the number of plant species were negatively correlated. Then, pH, WC, SOM, and TC were positively correlated with pc2. However, the number of plant species and vegetation coverage were negatively correlated. The PCA showed that pH had the smallest angle with pc1 and WC had the smallest angle with pc2 The sample plots are clustered to some degree by the habitats in the PCA biplot. The forest is significantly apart from other habitats, and little overlap occurred between the bamboo grove and wasteland and forest. There was no significant separation between the garden, bamboo grove, and grassland. 3.2. Characteristics of Pill Bugs' Population In total, 1015 individuals of pill bugs were captured and measured in our study. The number of individuals was 366 in the grassland, 201 in the bamboo grove, 171 in the garden, and 145 and 132 in the forest and wasteland, respectively. There were significant differences in body length (F4,1010 = 61.439, p < 0.001) and body weight (F4,1010 = 84.835, p < 0.001) of pill bugs among habitats. The mean body length and weight of all individuals in the five habitats were (8.21 +- 2.07) mm and (48.06 +- 32.68) mg, respectively. The mean body length and weight in the bamboo grove and grassland were smaller (7.52 +- 1.89) mm (36.34 +- 24.15) mg, (7.58 +- 1.86) mm (37.96 +- 25.33) mg, while the average body length and body weight of wasteland were larger (10.30 +- 1.44) mm (87.27 +- 31.17) mg. The body length and body weight of pill bugs in the forest and the garden were on the medium level . As the specific data obtained from the statistics indicate that most pill bugs were of medium body length. As shown in Figure 4, in total, body length <=7 mm accounted for 35.5%, 7-10 mm accounted for 43.3%, and l > 10 mm accounted for 21.3%. The lighter individuals were the majority. Individuals with body weight <= 50 mg accounted for 58.8%, 50~100 mg accounted for 32.4%, and m >100 mg accounted for 8.8%. The Chi-square test indicated that the distribution of body length (kh2 = 209.325, df = 8, p < 0.001) and weight (kh2 = 241.131, df = 8, p < 0.001) were significantly different among different habitats. There was a moderate correlation between habitat type and body length (Cramer's V = 0.321, p < 0.001), and between habitat type and body weight (Cramer's V = 0.345, p < 0.001). The post-hoc testing of the grouping composition indicated a higher proportion of bigger individuals (l >10 and m >100) were found in the wasteland with the highest residuals (>12). Furthermore, the lower proportion of bigger individuals (l >10 and m >100) were found in the grassland and bamboo grove with the lower residuals (<-4). The variation of the proportion and the residuals are shown in Table 3. There was a significant positive regression relationship between body weight (m) and body length (l) of the pill bugs . The exponential function equation is obtained as m = 1.89exp0.36l (R2 = 0.89, p < 0.001) and the linear regression equation is obtained as m = 14.78 l - 73.22 (R2 = 0.88, p < 0.001). We found that the power function equation is better able to present the relationship between body weight and body length. There was a significant positive regression relationship between body length and body weight in the selected urban spaces . 3.3. Correlation of Environmental Factors with Population Characteristics The body length and body weight of pill bugs was correlated with environmental factors . Results show that pH was strongly related to body length; TC, SOM, and the number of plant species were strongly related to body weight. There was no significant correlation with other environmental factors. The number of plant species presented a significant negative correlation to TC, SOM, and vegetation coverage. A significant positive correlation between SOM and TC was detected in this study. 4. Discussion 4.1. Differentiation of Soil Properties among Different Habitats The impact of rapid urbanization on urban ecosystems has received widespread attention . Changes in urban land use patterns provide opportunities to modify the high heterogeneity of urban green spaces, by scattering different habitat vegetation across urban areas . This helps to mitigate the negative effects of urbanization on native ecosystem biomes, and different vegetation cover also impacts soil physicochemical properties . The distribution of some groups of macrofauna has been suggested as a bioindicator of soil quality in previous studies . Our study indicates that different vegetation species lead to significant differences in some soil properties, such as SOM and TC. However, soil may keep a high consistency on a relatively small scale, because the soil in the habitats was the same when the campus was constructed in 2005. Although some human activities such as irrigation and fertilization might affect soil properties, no significant differences in the properties of TN and EC among the selected habitats occurred in our study . These different manifestations of soil properties may be related to the fact that there are also higher similarities in land use management practices among green spaces . In the artificial environment, the characteristics of the environment tend to be suitable for human habitation and aesthetic needs. Thus, although there are some differences in vegetation in different habitats, the soil environment has not been particularly distinct, showing relatively similar characteristics . 4.2. Relationship between Environmental Factors and Population Characteristics There are environmental differences in soil physicochemical properties in urban green spaces , and pill bugs are more sensitive to environmental changes . Population characteristics can reflect the environmental condition of urban green spaces to a certain extent; hence, the organism can be used as an indicator for the condition of the urban green space ecosystem . Pill bugs play an important role in recycling nutrients back into the ecosystem, and present important ecological significance. Furthermore, food quality had important effects on the dynamics of the experimental pill bugs' populations . Populations of pill bugs exhibited different patterns of life history which may be related to their food resources in previous studies . Studies have shown that there is a certain distribution pattern of soil macrofauna in different habitats and that the soil macrofauna with larger body sizes in habitats received a weaker influence of anthropogenic activities than those with smaller body sizes . In this study, food resources and human disturbances may work together to affect the characteristics of populations. The average body length and weight of pill bugs in the grassland were smaller at (7.58 +- 1.86) mm and (37.96 +- 25.33) mg, respectively, while the average body length and weight of wasteland pill bugs were larger at (10.30 +- 1.44) mm and (87.27 +- 31.17) mg. Characteristics of the grassland and the wasteland were more distinct than those of other habitats . However, we did not collect evidence about the reproduction characteristics of the population, and the species' reproduction and life cycle may also affect the body size and weight structure of the population . Furthermore, rainfall and temperature also have been mentioned as the influencing factors in the reproduction of pill bugs . In this study, there was a moderately strong correlation between habitat type and pill bugs' body characteristics (p < 0.001), with the larger and heavier individuals in the wasteland (l > 10 mm, m > 100 mg adjusted labeling residuals all > 12) (Table 3). Meanwhile, soil pH was strongly correlated with body length. TC, SOM, and vegetation species were strongly correlated with body weight . Besides being a key component of good soil structure, increasing the soil capacity of water and nutrient retention, SOM is the primary source of food for the soil biota; it is the base of the soil trophic pyramid. Additionally, the life cycle may present characteristics among habitats because of the variation of the food condition and soil environment . The significant differences in body size and weight among different habitats indicated that the population distribution would be responsive to the soil environment. Especially, soil pH and SOM may be the most important soil properties indicating the distribution of pill bugs. The larger pill bugs tended to be found in habitats with higher soil pH and lower SOM or TC. Though it is a pity that we cannot detect the variations in the life cycle which is related to body size and weight in a single season. However, this should be our next research on variations of the pill bugs' population with habitat change. 5. Conclusions Changes in soil properties along the vegetation types have a significant effect on the population characteristics of pill bugs. Land use management influenced soil physicochemical properties in urban spaces, and population characteristics changed along with the variation of soil properties. There were significant differences in WC, pH, TC, and SOM of soils among selected habitats, and no significant differences in other soil properties. In addition, the regression equation between body length and body weight was set and well-fitted with a significant positive correlation. The larger pill bugs were found in the wasteland, which may relate to the lower SOM and TC and less disturbance; the smaller pill bugs were found in the grassland and the bamboo grove, which may relate to the lower pH. Furthermore, the food resource and human disturbance may also contribute to the variation of body size and weight among habitats. Acknowledgments We would like to thank Lin Jiang, Qinghao Wang, Ruotong Li, Jingyi Shi, and Jiawen Hu who helped with collecting, preparing the soil samples, and measuring the pill bugs. Author Contributions Conceptualization, B.G. and L.Y.; methodology, B.G., H.L. and L.Y.; software, S.W. and B.G.; validation, S.W., Z.Z. and B.G.; formal analysis, S.W. and Z.Z.; investigation, Z.Z. and S.W.; resources, B.G. and H.L.; data curation, S.W.; writing--original draft preparation, B.G., S.W. and Z.Z.; writing--review and editing, B.G. and L.Y.; visualization, S.W.; supervision, B.G. and H.L.; project administration, L.Y.; funding acquisition, Z.Z. and B.G. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available on request from the corresponding author. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Study area and sampling site of Yancheng City, Jiangsu Province. Figure 2 The PCA biplot on soil properties and vegetation. Figure 3 Length (A) and weight (B) of pill bugs (mean +- S.D.) among different habitats. Note: different letters mean significant differences. Figure 4 The averaged proportion of length (A) and weight (B) (mean +- S.D.) in total based on each habitat. Figure 5 Regressions between body length and body weight of pill bugs. Figure 6 Correlation of habitat environmental factors with physical characteristics of pill bugs (Edge widths indicate Mantel's r statistics corresponding to distance correlations, and edge colors indicate statistical significance based on 9999 permutations showing pairwise comparisons of physical characteristics with environmental factors. The color gradient in the box indicates Pearson's correlation coefficient, the magnitude of which is proportional to the r-value, and the number indicates Pearson's r-value. The "*" means p < 0.050; The "**" means p < 0.01 for Pearson correlation.) animals-13-00857-t001_Table 1 Table 1 Descriptions of vegetation types in the selected study area. Vegetation Types Plant Height (m) Main Plant Species Bamboo grove 6.0 Phyllostachys glauca Forest 5.0 Prunus subg. Cerasus, Ligustrum lucidum, Koelreuteria paniculata Garden 0.5 Orychophragmus violaceus Grassland 0.3 Zoysia tenu ifolia, Cynodon dactylon, Imperata cylindrica, Lolium perenne Wasteland 3.0 Sapium sebiferum, Broussonetia papyrifera, Galium odoratum, Vicia sativa, Sonchus asper animals-13-00857-t002_Table 2 Table 2 Soil properties and vegetation in different habitats (mean+- S.D.). Note: different letters in each row mean significant differences while no mark means no significant difference. Habitat Bamboo Grove Forest Garden Grassland Wasteland Total WC (%) 12.11 +- 7.36 ab 20.54 +- 3.43 a 18.06 +- 1.37 a 10.39 +- 1.75 b 13.73 +- 2.13 ab 14.97 +- 5.24 pH 6.93 +- 0.05 b 7.17 +- 0.11 a 6.91 +- 0.06 b 6.96 +- 0.15 b 7.12 +- 0.05 a 7.02 +- 0.14 SOM (g kg-1) 27.72 +- 1.89 a 22.04 +- 3.75 a 26.40 +- 4.04 a 24.90 +- 1.65 a 13.80 +- 6.59 b 22.96 +- 6.24 TC (g kg-1) 25.88 +- 4.76 a 18.90 +- 3.21 ab 25.50 +- 6.10 a 22.62 +- 1.36 a 13.66 +- 2.21 b 21.31 +- 5.89 TN (g kg-1) 3.28 +- 0.36 2.72 +- 0.23 3.50 +- 0.60 3.10 +- 0.14 2.94 +- 1.09 3.10 +- 0.61 EC (us cm-1) 17.13 +- 1.52 14.61 +- 2.57 16.02 +- 1.23 14.88 +- 3.31 13.53 +- 1.21 15.23 +- 2.32 AN (mg kg-1) 11.54 +- 1.40 11.93 +- 1.36 13.48 +- 2.08 10.58 +- 2.15 11.69 +- 2.45 11.84 +- 2.01 AP (mg kg-1) 22.38 +- 3.10 24.18 +- 2.63 26.69 +- 2.50 22.95 +- 1.14 22.95 +- 2.55 23.83 +- 2.75 Number of plant species(n) 1.40 +- 0.55 b 5.00 +- 0.71 a 1.60 +- 0.89 b 3.80 +- 0.84 ab 6.00 +- 0.20 a 3.56 +- 2.12 Vegetation coverage(%) 98.00 +- 4.47 a 56.00 +- 5.47 b 96.00 +- 2.24 a 97.00 +- 4.47 a 87.00 +- 2.73 a 86.80 +- 16.63 animals-13-00857-t003_Table 3 Table 3 The proportion and the residuals (in parentheses) of grouping composition by body length and body weight among different habitats. Habitat Bamboo Grove Forest Garden Grassland Wasteland Total Length/mm l <= 7 9.0% (3.2) 3.4% (-3.1) 5.6% (-0.6) 17.1% (6.0) 0.3% (-8.5) 35.5% 7< l <= 10 8.7% (0.2) 7.6% (2.6) 6.7% (-1.0) 15.6% (0.0) 4.7% (-1.7) 43.3% l > 10 2.2% (-4.0) 3.3% (0.5) 4.5% (2.0) 3.3% (-7.0) 8.0% (12.1) 21.3% Weight/mg m <= 50 14.3% (4.3) 8.3% (-0.2) 8.6% (-2.3) 25.6% (5.9) 2.1% (-10.7) 58.8% 50 < m <= 100 5.3% (-1.9) 3.9% (-1.3) 7.3% (3.3) 9.8% (-2.7) 6.1% (3.8) 32.4% m > 100 0.2% (-4.4) 2.1% (2.6) 1.0% (-1.5) 0.7% (-5.8) 4.8% (12.3) 8.8% Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000218 | The objective was to determine the effects of drying and blanching methods on the nutrient utilization of black soldier fly larva (BSFL; Hermetia illucens) meal by pigs using in vitro assays. Two-step and three-step in vitro assays were employed to simulate the gastrointestinal tract of pigs. Four BSFL meals were prepared using the following pretreatment methods: (1) microwave drying at 80 degC for 32 min, (2) hot-air drying at 60 degC for 17 h, (3) blanching for 5 min in boiling water and hot-air drying at 60 degC for 17 h, and (4) 2% citric acid solution blanching for 5 min in boiling solution and hot-air drying at 60 degC for 17 h. After the drying process, each BSFL was defatted and ground to obtain BSFL meals. The nitrogen (N) concentration in the test ingredients ranged from 8.5 to 9.4%, and the ether extract ranged from 6.9 to 11.5% on an as-is basis. The amino acid (AA) concentration in the BSFL meals ranged from 2.80 to 3.24% for Lys and 0.71 to 0.89% for Met on an as-is basis. Hot-air-dried BSFL meal had a greater in vitro ileal disappearance (IVID) of N compared with microwave-dried BSFL meal (p < 0.05). However, blanched BSFL meals in water or 2% citric acid solution before hot-air drying had a lower (p < 0.05) IVID of N compared with microwave-dried or hot-air-dried BSFL meal. Blanched BSFL meals in water or 2% citric acid solution before hot-air drying showed a lower (p < 0.05) in vitro total tract disappearance of dry matter and organic matter compared with microwave-dried or hot-air-dried BSFL meal. Microwave-dried BSFL meal had a lower (p < 0.05) IVID of indispensable AA, except for His, Lys, Met, and Phe, compared with hot-air-dried BSFL meals. However, blanched BSFL meals in water or 2% citric acid solution before hot-air drying showed a lower (p < 0.05) IVID of indispensable AA compared with microwave-dried or hot-air-dried BSFL meal. In conclusion, hot-air-dried BSFL meal presented greater nutrient utilization compared with microwave-dried BSFL meal for pigs. However, blanching in water or citric acid solution negatively affected the nutrient digestibility of BSFL meal based on in vitro assays. black soldier fly larva meal blanching method drying method in vitro assays pigs The research received no external funding. pmc1. Introduction Fish meal and soybean meal are widely used in the swine feed industry as protein sources due to their high concentrations of digestible amino acids (AA). However, the price fluctuation of fish meal and soybean meal has increased the demand for alternative feed ingredients such as an insect protein . Black soldier fly (Hermetia illucens) larva (BSFL) meal is considered as an alternative ingredient due to its high crude protein (CP) concentration. Research on BSFL meal as a protein source for pigs has increased . Black soldier fly larva meal is potentially contaminated with microorganisms including Salmonella, Escherichia coli, Staphylococcus aureus, and Bacillus cereus, because of their rearing conditions . Therefore, a disinfection process must precede the use of BSFL as a feed ingredient . Drying is widely used to prevent microbial growth and increase the shelf life of insect protein . Various drying methods have been conducted for producing insect protein, including hot-air drying, microwave drying, freeze drying, and roasting. Additionally, blanching is a pretreatment that is usually applied before the drying process to destroy microorganisms and inactivate enzymes . These processing procedures also affect the nutritional values of BSFL meal . However, the literature examining the influence of blanching and drying methods on the nutrient utilization of BSFL meals is scarce. In vitro assays have been widely used to determine the nutrient utilization of feed ingredients for pigs, and the in vitro results are highly correlated with in vivo experiments . To our knowledge, the effects of blanching and drying methods on the nutrient utilization of BSFL meal based on in vitro assays have not been documented. Therefore, the objective of the present study was to determine the effects of blanching and different drying methods on the nutrient utilization of BSFL meal by pigs based on in vitro assays. 2. Materials and Methods 2.1. Preparation of Black Soldier Fly Larva Meals The BSFL were reared at 25 to 32 degC and 60 to 70% relative humidity for 15 days at a commercial black soldier fly farm (Entomo Co. Ltd., Cheongju, Republic of Korea). Dried food waste was fed to BSFL once during the whole growth duration following Control of Livestock and Fish Feed Act No. 14481 in Korea. On day 15, the BSFL were divided into four batches and dried using four different slaughter and drying procedures: (1) microwave drying at 80 degC for 32 min using a microwave (M-200, Entomo Co. Ltd., Cheongju, Republic of Korea); (2) hot-air drying at 60 degC for 17 h using a forced-air drying oven (KAPD-195D; CNT Co. Ltd., Gwangju, Republic of Korea); (3) blanching for 5 min in boiling water and hot-air drying at 60 degC for 17 h using a drying oven; and (4) 2% citric acid solution blanching for 5 min in boiling solution and hot-air drying at 60 degC for 17 h using a drying oven. The hot-air drying time was used to obtain a similar degree of dryness compared to the microwave drying process for 32 min. The blanching of BSFL for 5 min was based on the suggestion of the IPIFF . After the drying process, oil was extracted from the BSFL at 45 degC using a screw-type cold press oil machine (NF-80; Karaerler Makina, Ankara, Republic of Turkiye). 2.2. In Vitro Procedures A 2-step in vitro procedure was performed to measure the in vitro ileal disappearance (IVID) of dry matter (DM), nitrogen (N), and AA in the BSFL meals by simulating the digestion and absorption in the stomach and the small intestine of pigs . In the first step of the procedure mimicking the digestion conditions of the pig stomach, 1 g of a BSFL sample was transferred into a 100 mL conical flask, and then 25 mL of sodium phosphate buffer solution (0.1 M, pH 6.0) and 10 mL of HCl (0.2 M, pH 0.7) were added to the flask. The pH was adjusted to 2.0 using 1 M HCl and 1 M NaOH solution, and 1 mL of freshly prepared pepsin solution (10 mg/mL; >= 250 units/mg solid, P7000, pepsin from porcine gastric mucosa; Sigma-Aldrich, St. Louis, MO, USA) was added to the flask. To inhibit microbial growth, 0.5 mL of chloramphenicol (C0378, chloramphenicol; Sigma-Aldrich, St. Louis, MO, USA) solution (5 g/L ethanol) was also added to the flask. The flasks sealed with a silicone cap were incubated in a shaking incubator (LSI-3016R; Daihan Labtech, Namyangju, Republic of Korea) at 39 degC for 6 h, and the incubator was set at 125 rpm. After the incubation, the second step of the in vitro procedure mimicking the digestion and absorption in the small intestine of pigs was performed. Firstly, 10 mL of phosphate buffer solution (0.2 M, pH 6.8) and 5 mL of 0.6 M NaOH solution were added to the flasks. Then, the pH was adjusted to 6.8 using 1 M HCl or NaOH solution, and 1 mL of freshly prepared pancreatin solution (50 mg/mL; 4 x USP, P1750, pancreatin from porcine pancreas; Sigma-Aldrich, St. Louis, MO, USA) was added. Thereafter, the flasks were incubated in the shaking incubator (LSI-3016R; Daihan Labtech, Namyangju, Republic of Korea) at 39 degC for 18 h, and the incubator was set at 125 rpm. After the incubation, 5 mL of 20% sulfosalicylic acid solution was added to the flasks, which were left for 30 min at room temperature to precipitate indigestible proteins. After the 30 min precipitation, undigested residues were filtered through dried glass filter crucibles (Filter Crucibles CFE Por. 2; Robu, Hattert, Germany) containing 500 mg of Celite, which helped to inhibit the plugging of the filter by the potentially gelatinous residues. The flasks were rinsed twice with 1% sulfosalicylic acid solution, and 10 mL of 95% ethanol and 10 mL of 99.5% acetone were added twice to the filter crucibles. The filter crucibles with undigested residues were dried at 80 degC for 24 h. After cooling in a desiccator for 1 h, the glass filter crucibles were weighed to calculate the IVID of DM in the BSFL meals. The undigested residues in filter crucibles were collected and analyzed for N contents to calculate the IVID of N. To determine the AA concentration of undigested residues of BSFL, the undigested residues obtained from 10 flasks were pooled within treatments to obtain a sufficient amount of residues for AA analysis. During the 2-step in vitro procedure, a blank was used to correct the DM, N, and AA contents in the residues that did not originate from the BSFL meals. To simulate total tract digestion and absorption, the in vitro total tract disappearance (IVTTD) of DM in the BSFL meals was measured using a 3-step in vitro technique that simulated the digestion and absorption in the stomach, the small intestine, and the large intestine of pigs . The first and second steps were similar to the IVID procedure, differing in the weight of the sample, the concentration of the enzymes, and the incubation time. For the IVTTD, 0.5 g of each sample was used, and the concentrations of pepsin and pancreatic solutions were increased to 25 and 100 mg/mL, respectively, while the incubation time for steps 1 and 2 were reduced to 2 and 4 h, respectively. In the third step of the IVTTD procedure, 10 mL of 0.2 M EDTA solution was added to the samples. The pH was then adjusted to 4.8. Samples were supplemented with 0.5 mL of multi-enzyme solution (V2010, Viscozyme; Sigma-Aldrich, St. Louis, MO, USA) as a substitute for microbial enzymes and incubated in a shaking incubator for 18 h at 39 degC, and the incubator was set at 125 rpm. After the 18 h incubation, the samples were filtered, and the undigested residues were collected and dried as previously described in the IVID procedure, except that the residues were dried at 130 degC for 6 h. In addition, ash concentrations in the undigested residues were measured to calculate the IVTTD of OM in the BSFL meals. During the 3-step in vitro procedure, a blank was used to correct the DM and OM contents in the residues that did not originate from the BSFL meals. All in vitro procedures were performed in 3 replicates. 2.3. Chemical Analyses The test ingredients and in vitro undigested residues were analyzed for DM . The nitrogen (method 976.05) and OM (method 942.05) in the test ingredients and in vitro undigested residues were also analyzed as described in AOAC . The test ingredients were also analyzed for ether extract (EE; method 920.39), ash (method 942.05), and acid detergent fiber (ADF; method 973.18), and chitin was calculated as the difference between the concentrations of ash-free ADF and ADF-linked protein . The AA concentrations of the test ingredients and in vitro undigested residues were determined by ion-exchange chromatography using post-column derivatization with ninhydrin. Before the analysis, samples were liberated from the protein by hydrolysis with 6 N HCl for 24 h at 110 degC, as described in AOAC (method 982.30) . Methionine and cystine were analyzed as methionine sulfone and cysteic acid after cold performic acid oxidation overnight before hydrolysis. All chemical analyses were performed in duplicate. 2.4. Calculations and Statistical Analyses The IVID or IVTTD of DM was calculated using the following equation from Choi et al. :IVID or IVTTD of DM (%) = [DMTI - (DMUR - DMBlank)] / DMTI x 100 where DMTI (g) is the amount of test ingredients on a DM basis, DMUR (g) is the amount of undigested residue on a DM basis after in vitro assays, and DMBlank (g) is the amount of DM residue on a DM basis after in vitro digestion procedures in the blank. After the 2-step in vitro assay, the undigested residues and celite were collected, weighed, and analyzed for N and AA. Then, the IVID of N or AA was calculated using the following equation modified from Kim et al. :IVID of N or AA (%) = [(DMTI x CTI) - {(DMUR x CUR) - (DMBlank x CBlank)}] / (DMTI x CTI) x 100 where CTI, CUR, and CBlank (g) are the N or AA concentration (%) expressed on a DM basis in the test ingredients, undigested residue after 2-step in vitro assays, and blank, respectively. After the 3-step in vitro assay, the undigested residues and celite were collected, weighed, and analyzed for OM. Then, the IVTTD of OM was calculated using the following equation:IVTTD of OM (%) = [(DMTI x OMTI) - {(DMUR x OMUR) - (DMBlank x OMBlank)}] / (DMTI x OMTI) x 100 where OMTI, OMUR, and OMBlank (g) are the OM concentration (%) expressed on a DM basis in the test ingredients, undigested residue after 3-step in vitro assays, and blank, respectively. Experimental data were analyzed using the GLM procedure of SAS (SAS Inst. Inc., Cary, NC, USA). The test ingredient was included as a fixed variable in the model. The least squares means were calculated for the IVID of DM, N, and AA and the IVTTD of DM and OM for each test ingredient and compared using the PDIFF option with Tukey's adjustment. Each flask was considered as the experimental unit for the in vitro disappearance of nutrients, and a pooled sample from 10 flasks was considered as the experimental unit for the IVID of AA. The statistical significance was declared at p < 0.05. 3. Results The ash and N concentrations in the four sources of BSFL meal ranged from 12.9 to 22.0% and from 8.5 to 9.4% (as-is basis), respectively (Table 1). The EE in the test ingredients ranged from 6.9 to 11.5%, and the chitin in the test ingredients ranged from 4.3 to 7.2%. The analyzed Lys concentrations in the four BSFL meals ranged from 2.80 to 3.24%, and the Met concentrations ranged from 0.71 to 0.89%. Hot-air-dried BSFL meal had a greater IVID of N compared with microwave-dried BSFL meal (p < 0.05; Table 2). However, blanched BSFL meal in water or 2% citric acid solution before hot-air drying had a lower IVID of N (p < 0.05) compared with microwave-dried or hot-air-dried BSFL meal. Blanched BSFL meal in water or 2% citric acid solution before hot-air drying showed a lower IVTTD of DM (p < 0.05) and OM (p < 0.05) compared with microwave-dried or hot-air-dried BSFL meal. The IVTTD of OM in blanched BSFL meal in 2% citric acid solution before hot-air drying was greater than that in blanched BSFL meal in water before hot-air drying. The IVID of Arg, Ile, Leu, and Thr in microwave-dried BSFL meal was lower (p < 0.05) than that in hot-air-dried BSFL meal without blanching but greater (p < 0.05) than that in blanched BSFL meals in water or 2% citric acid solution before hot-air drying (Table 3). The IVID of His, Lys, Met, and Phe in microwave-dried or hot-air-dried BSFL meal was greater (p < 0.05) compared with that in blanched BSFL meals in water or 2% citric acid solution before hot-air drying. The IVID of Ile in blanched BSFL meal in water before hot-air drying was greater (p < 0.05) than that in blanched BSFL meal in 2% citric acid before hot-air drying. 4. Discussion Black soldier fly larvae are regarded as a promising protein source due to their high N concentrations and the high gain-to-feed ratio of fly production . Considering the rearing conditions of black soldier fly, BSFL meals may be contaminated with microbial pathogens, and thus a disinfection process is necessary to produce safe feed ingredients. Various heat treatments are used to reduce the microbial risk and increase the shelf life of BSFL meals . However, these heat treatments potentially affect the physicochemical properties to varying degrees, depending on the drying temperature and time. In a previous study, microwave drying affected the AA profiles and increased the size of protein particles in BSFL meal . In addition, hot-air drying can stimulate the denaturation of proteins, lipid oxidation, and melanization . Blanching prior to drying can also cause the alteration of the nutrient composition and texture of insect protein . These changes in physicochemical properties might alter the nutrient utilization of BSFL meals, which can be evaluated using in vitro assays. To our knowledge, however, the effects of blanching and drying methods on the in vitro disappearance of nutrients in BSFL meal for pigs have not been documented. In the present work, the effects of blanching and drying methods on the nutrient utilization of BSFL meals by pigs were determined using an in vitro assay. The analyzed chemical compositions of BSFL meals in the current work were mostly within the ranges of previous studies . However, the ash concentrations of the four sources of BSFL meal were higher than the values in previous studies . In addition, the EE concentrations of the BSFL meals, except for the BSFL meal blanched in 2% citric acid solution before hot-air drying, were lower than in previous studies . The reason for this discrepancy may have been the different rearing conditions of the BSFL and the processing methods for euthanizing, drying, and oil extraction . Although the four BSFL meals were reared under the same environmental conditions and fed the same diets, the ash concentrations in the four BSFL meals varied in the present study. Bawa et al. reported that the ash concentration in microwave-dried crickets (Henicus whellani) was greater than that in hot-air-dried crickets. This finding is consistent with the results from the present study. Mshayisa et al. reported that the addition of acid to the solution decreased the pH of the solution and the protein solubility, which facilitated the layer separation of BSFL meal during the oil extraction process and the removal of the mineral fraction. Similarly, Soetemans et al. also reported that the use of organic acids improved the fractionation of the BSFL into protein factions. During blanching, potential losses of protein are minimized at pH 5, which was achieved in 2% citric acid in the present work. In terms of EE, the effects of the drying and blanching methods were also inconsistent. In a previous study , scalding in boiling water before hot-air drying for 4 min increased the EE concentration in BSFL meal. In another study , however, water blanching before freeze drying did not change the lipid content of the BSFL meal, in agreement with the present study. Although it is uncertain why water blanching did not affect the EE concentration of BSFL meal, the deviations in the EE concentrations may have been due to factors including the rearing conditions, oil extraction process, and storage conditions. The reason for the high ADF and chitin in BSFL meals blanched in water or 2% citric acid solution was unclear. Although examining a different species, Fox et al. reported that water blanching before drying increased the chitin concentration in shrimp head meal. Water blanching before hot-air drying increased the N and indispensable AA concentrations in BSFL meals. This observation was consistent with a previous study . The in vitro disappearance of nutrients in BSFL meals in the present work was within the range of previously reported values , but the IVID of N in BSFL meals blanched in water or 2% citric acid before hot-air drying was slightly lower than that in previous studies . The decreased IVID of N in BSFL meals after water or 2% citric acid blanching followed by hot-air drying was likely due to the high concentration of chitin in these BSFL meals. Chitin is poorly digested by the endogenous digestive enzymes of pigs and is negatively correlated with nutrient utilization . Additionally, chitin is a major fiber fraction in the exoskeleton of insects and contains chitinous N, which is one of the major reasons for the overestimation of CP concentrations in insect meals . The higher IVID of N in hot-air-dried BSFL meals than microwave-dried BSFL meal in the present work was in agreement with previous findings . Shorstkii et al. also reported that microwave drying denatured and polymerized the protein particles of BSFL, and it was harder for the digestive enzymes to digest the denatured proteins. The effects of blanching on the IVID of N varied among the studies. Manditsera et al. reported that boiling for 30 min did not affect the in vitro protein hydrolysis of roasted beetle (Eulepida mashona) and cricket (Henicus whellani). However, Zielinska et al. reported that 10 min boiling improved the degree of hydrolysis in mealworm (Tenebrio molitor) and desert locust (Schistocerca gregaria), and Singh et al. reported that blanching improved the in vitro CP digestibility of house cricket (Acheta domesticus). This discrepancy may be attributed to the differences in species, in vitro procedures, and boiling times. The ranking of the IVID of AA among the test ingredients was similar to that of the IVID of N for pigs. This finding indicated that the IVID of N in BSFL meal was positively correlated with the IVID of AA in BSFL meal. In a previous in vitro experiment simulating the human gastrointestinal tract conducted by Huang et al. , the in vitro digestibility of all AA in hot-air-dried BSFL meal was higher than that in microwave-dried BSFL meal. This finding was consistent with the IVID of some AA in the present study and indicates that BSFL meal dried using a microwave is harder to digest than hot-air-dried BSFL meal. Along with N digestibility, water or 2% citric acid blanching also decreased the IVID of indispensable AA in BSFL meal. To the best of our knowledge, the in vitro AA digestibility in BSFL meal for pigs was reported herein for the first time. Like the IVID of N, the decreased IVID of AA after blanching was likely due to the increased chitin concentration. Additionally, chitin may form aggregates with digestive enzymes and decrease the IVID of AA. The addition of 2% citric acid during the blanching before hot-air drying decreased the IVID of Ile. The reason for this decrease in the IVID of Ile after 2% citric acid solution blanching prior to hot-air drying was not clear, and further research is needed to clarify the effect of blanching in citric acid on the IVID of Ile. 5. Conclusions In conclusion, the addition of citric acid during blanching before hot-air drying increased the N concentration and decreased the ash concentration of BSFL meal. Hot-air-dried BSFL meal presented greater nutrient utilization by pigs compared with microwave-dried BSFL meal. However, blanching in water or citric acid solution negatively affected the nutrient digestibility of BSFL meal for pigs based on in vitro assays. Author Contributions Conceptualization, S.H.P., H.J.J. and B.G.K.; methodology, J.S. and B.G.K.; formal analysis, J.S. and S.J.Y.; investigation, J.S., S.H.P. and H.J.J.; data curation, J.S.; writing--original draft preparation, J.S.; writing--review and editing, S.H.P., H.J.J., S.J.Y. and B.G.K.; supervision, B.G.K. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data presented in the current work are available. Conflicts of Interest The authors declare no conflict of interest. animals-13-00858-t001_Table 1 Table 1 Analyzed chemical compositions of four black soldier fly larva meals with various drying and blanching methods, as-is basis 1. Item, % Drying Method: Microwave Hot-Air Hot-Air Hot-Air Blanching: - - Water 2% Citric Acid Solution Dry matter 96.8 96.1 97.4 97.6 Organic matter 74.8 80.6 81.8 84.7 Ash 22.0 15.5 15.6 12.9 Nitrogen 8.5 8.9 9.4 9.1 Ether extract 6.9 7.4 7.4 11.5 Acid detergent fiber 10.8 12.7 18.8 17.6 Chitin 2 4.3 4.8 7.1 7.2 Indispensable amino acids Arg 2.43 2.55 2.79 2.56 His 1.43 1.43 1.71 1.46 Ile 2.14 2.31 2.48 2.11 Leu 3.32 3.62 3.93 3.57 Lys 2.80 2.96 3.24 2.88 Met 0.71 0.86 0.89 0.88 Phe 1.99 2.28 2.42 2.10 Thr 1.96 2.12 2.23 2.09 Val 4.39 4.27 5.49 5.14 Dispensable amino acids Ala 3.39 3.82 3.56 3.43 Asp 4.42 4.76 5.11 4.85 Cys 0.38 0.42 0.38 0.36 Glu 6.42 6.06 6.59 6.39 Gly 2.69 2.65 3.08 2.89 Pro 3.15 3.08 3.45 3.23 Ser 2.19 2.23 2.49 2.32 Tyr 2.98 3.03 3.64 3.28 1 Samples were analyzed in duplicates. 2 Chitin (%) = ash-free acid detergent fiber (%)--acid detergent fiber-linked protein (%). animals-13-00858-t002_Table 2 Table 2 In vitro ileal disappearance (IVID) of dry matter (DM) and nitrogen (N) and in vitro total tract disappearance (IVTTD) of DM and organic matter (OM) in four black soldier fly larva meals with various drying and blanching methods for pigs 1. Item, % Drying Method: Microwave Hot-Air Hot-Air Hot-Air SEM p-Value Blanching: - - Water 2% Citric Acid Solution IVID of DM 84.6 a 84.8 a 80.1 b 82.9 ab 0.6 0.003 IVID of N 84.4 b 86.7 a 81.3 c 82.5 c 0.3 <0.001 IVTTD of DM 90.4 a 89.6 a 85.0 b 84.5 b 0.3 <0.001 IVTTD of OM 85.7 b 86.6 a 80.6 d 81.5 c 0.1 <0.001 SEM = standard error of the means. 1 Each least squares mean represents three observations. a-d Least squares means with a row without a common superscript letter differ (p < 0.05). animals-13-00858-t003_Table 3 Table 3 In vitro ileal disappearance of amino acids in four black soldier fly larva meals with various drying and blanching methods for pigs 1. Item, % Drying Method: Microwave Hot-Air Hot-Air Hot-Air SEM p-Value Blanching: - - Water 2% Citric Acid Solution Indispensable amino acids Arg 94.4 b 96.5 a 90.7 c 90.8 c 0.3 <0.001 His 93.8 a 95.6 a 89.6 b 87.7 b 0.5 <0.001 Ile 91.5 b 94.0 a 87.8 c 85.1 d 0.4 <0.001 Leu 90.7 b 92.8 a 85.7 c 86.5 c 0.4 <0.001 Lys 93.6 a 92.3 a 89.9 b 87.8 c 0.4 <0.001 Met 88.8 a 91.4 a 81.9 b 83.2 b 0.8 <0.001 Phe 89.1 a 89.7 a 85.0 b 83.1 b 0.9 0.002 Thr 90.8 b 92.7 a 86.7 c 87.7 c 0.4 <0.001 Dispensable amino acids Ala 92.5 b 94.2 a 88.3 d 89.7 c 0.3 <0.001 Asp 91.1 b 93.2 a 86.8 d 88.5 c 0.3 0.005 Cys 82.5 a 81.3 ab 77.3 bc 75.3 c 1.1 <0.001 Glu 94.2 a 94.5 a 91.3 c 92.3 b 0.2 <0.001 Gly 87.2 a 88.7 a 81.1 b 82.4 b 0.6 <0.001 Pro 94.3 a 94.3 a 90.3 b 90.6 b 0.3 <0.001 Ser 90.6 a 91.8 a 87.0 b 87.8 b 0.4 <0.001 Tyr 93.1 a 94.7 a 89.1 b 88.3 b 0.5 <0.001 SEM = standard error of the means. 1 Each least squares mean represents three observations. a-d Least squares means with a row without a common superscript letter differ (p < 0.05). Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000219 | The objective was to evaluate the effects of palm kernel cake (PKC) supplementation on voluntary feed intake, in situ rumen degradability and performance in the wettest (WS--January to June) and less rainy seasons (LR--July to December) in the eastern Amazon. A total of 52 crossbred buffaloes that were neither lactating nor gestating were used, with 24 for the LR, aged 34 +- 04 months and an initial average weight of 503 +- 48 kg, and 24 for the WS aged 40 +- 04 months with an average weight of 605 +- 56 kg. The four treatments (levels of PKC in relation to body weight) were distributed in a completely randomized design, with 0% (PKC0), 0.25% (PKC0.2), 0.5% (PKC0.5) and 1% (PKC1) with six repetitions. The animals were housed in Marandu grass paddocks, intermittently, with access to water and mineral mixture ad libitum. Degradability was evaluated by the in situ bag technique in four other crossbred buffaloes with rumen cannulae, in a 4 x 4 Latin square (four periods and four treatments). The inclusion of PKC increased supplement consumption and production of ether extracts and reduced the intake of forage and non-fibrous carbohydrates. The dry matter degradability of Marandu grass was not affected; however, the fermentation kinetics in neutral detergent fiber (NDF) differed between the treatments. The co-product dry matter colonization time was greater in PKC1 and the highest effective degradability rates were from PKC0, but the productive performance of the animals was not influenced. Supplementation of buffaloes with PKC is recommended for up to 1% of body weight. co-products oilseed nutrition buffaloes weight gain Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)--Brasil001 This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)--Brasil (Finance Code 001). pmc1. Introduction Livestock is seen as an intensifier of the deforestation process in the Amazon. As a result, strategies such as the supplementation of animals in an extensive management system has been improved, aiming to combine improvements in production with better use of available areas . In this sense, the use of by-products has proved to be an interesting alternative to corn or soybean meals, since in addition to making use of agro-industry residues, it has low market value and good nutritional potential as a replacement for traditional ingredients . Its inclusion in ruminant diets, in addition to reducing environmental impacts, promotes the intensification of animal management systems and can help to increase productivity per area . Among available co-products, palm kernel cake (PKC) from the dende palm (Elaeis guineensis) stands out, because, in addition to its low cost and increasing availability, it has a dry matter content between 88.11 and 97.7%, ash between 3.01 and 7.82%, ethereal extracts ranging from 5.7 to 13.55%, crude protein between 13.01 and 18.23%, and neutral detergent fiber from 64.09 to 81.85% . However, PKC has a high content of acid-detergent fiber, which is slowly degraded and can restrict feed intake, degradability, and animal performance . Thus, for better use in animal feed, it is important to know its behavior in the rumen environment, its effect on other ingredients in the diet, and its inclusion limit. The hypothesis of this study is that there exists a supplementation level of PKC in buffalo diets that can maximize productive performance in pasture-grazed animals. Thus, the objective of this study was to evaluate voluntary feed intake, in situ rumen degradability and productive performance of buffaloes in an intermittent stocking system supplemented with palm kernel cake in the eastern Amazon. 2. Materials and Methods 2.1. Ethics Committee and Experiment Location All procedures with the animals were performed with authorization from the Ethics Committee on the Use of Animals of Embrapa Eastern Amazon, under protocol No. 007/2015. The experiment was carried out at the Animal Research Unit "Dr. Felisberto Camargo" (01deg25' S and 48deg26' W), belonging to Embrapa Eastern Amazon, municipality of Belem, Para, Brazil. The climate is Afi in the Koppen classification, A--humid, tropical climate with no cold period and with average monthly temperature of the warmest month above 18 degC; f--tropical forest climate with rainfall relatively abundant throughout the year, and i--the amplitude between the average temperatures of the warmest and coldest months is less than 5 degC with an average rainfall of 3001 mm/year, well distributed over the months. The average annual temperature and relative humidity are 26 degC and 86%, respectively, with the wettest period (WS) between January and June and the least rainy (LR) from July to December. 2.2. Animals and Experimental Design To evaluate feed intake and performance, the study design used 24 buffaloes, non-lactating and not pregnant, with initial body weight of 503 +- 48 kg and approximately 34 months of age (LR), and another 24 with initial body weight of 605 +- 56 kg and 40 +- 04 months of age (WS), distributed in a completely randomized design, with 4 treatments (PKC levels), 6 repetitions (animals) and repeated measures in time (LR and WS). Inclusion levels were: 0% (control treatment), and 0.25; 0.50 and 1% of body weight (BW). For degradability, 4 buffaloes with rumen cannula, in a 4 x 4 Latin square (4 periods and 4 treatments) were used. 2.3. Experimental Diets and Chemical Analyses Supplementation was offered once a day, at 08:00 h, in a stable with individual stalls. Furthermore, the animals were kept in 8 paddocks (1.2 ha) of Urochloa brizantha grass (syn. Brachiaria brizantha) cv. Marandu (Marandu grass), totaling an area of 9.6 ha, and provided with water and mineral mixture ad libitum in an intermittent stocking system, with 4 days of occupation and 28 days of rest. For greater acceptance of the supplement, the animals underwent a period of adaptation to the diet and management (21 days), and 0.15% of body weight of wheat bran was included in all treatments (Table 1). The forage mass was measured using the double sampling method, where destructive estimates were associated with canopy height . Every 90 days, 60 height readings were measured and recorded, at random, in all experimental paddocks, using a graduated cane, and forage samples were collected at ground level at 9 predetermined points (3 of shortest height, 3 medium height and 3 tallest). In the laboratory, 2 samples composed of whole plants were generated (pool of samples of height), which were dried in an oven (55 degC for 72 h) and weighed again to determine the forage/picket mass and chemical composition. Subsequently, samples were ground in a Wiley mill using a 1 mm sieve for dry matter (DM; method 934.01), ash (Ash; method 930.05), crude protein (CP; method 981.10) and ether extract (EE; method 920.39) . The content of neutral detergent fiber (NDF) and fiber in acid detergent (ADF) was determined according to . Non-fibrous carbohydrates (NFC) in diets were calculated according to , where NFC% = 100% - [CP% + NDF% + EE% + Ash%]. Grass samples were collected by simulated grazing (every 90 days), performed by trained professionals, to evaluate the portion consumed by the animals . 2.4. Voluntary Feed Intake and Performance The feed intake of the supplement and nutritional components was determined by the difference between the amount contained in the provided feed and the amount contained in the leftovers. Daily, before the new portion of supplement was offered, the leftovers were collected and weighed to determine the dry matter consumption, and this was used to adjust the next portion to allow 15% of leftovers. To estimate fecal production (kg DM/feces/day), titanium dioxide (TiO2) was used as an external indicator (10 g/animal/day), applied directly into the esophagus through a probe. The indicator was given for 7 days for adaptation purposes to obtain a homogeneous plateau of excretion . The determination of TiO2 content was performed by collecting feces, directly from the rectal ampulla, in the 24 animals, during the 2 experimental periods (LR and WS), from the eighth day of administration. The samples were packed in plastic packaging and kept at -20 degC. At the end of the period, the samples from each animal were homogenized, constituting a composite sample (sample/animal) and then pre-dried, ground and packed in flasks. A sample of 0.5 g of feces was digested for 2 h at 400 degC and, soon after, 10 mL of H2O2 (30%) was slowly added and completed with distilled water until it reached twice the volume. Subsequently, the material was transferred to 100 mL flasks and 3 drops of H2O2 (30%) were added . Feces, simulated grazing material, supplements and leftovers were analyzed for DM, CP, EE and ash , for NDF and ADF by the sequential method , and in vitro dry matter digestibility (DIVDM), simulated grazing and PKC . Fecal excretion was calculated using the formula: FE = TiO2 (administered (g/day))/TiO2 (existing in fecal DM (g/kg)). The feces of each animal were weighed, dried (55 degC +- 5 degC, for 72 h) and ground to pass a 2 mm sieve to determine the indigestible neutral detergent fiber (NDFi) and, later, the material was ground to pass a 1 mm sieve to evaluate the chemical composition. To estimate individual forage consumption (FC) (DM), the internal marker (NDFi) was used . The estimation of dry matter consumption was carried out from the Equation:FC(g/dia)=[(EF(g/day) x FCNDFi(%) / 100) - ISNDFi (g/day)]CIFOR NDFi(%) x100 where FC = individual forage consumption in g/day; EF = fecal excretion in g/day; CIFNDFi = concentration of NDFi in feces in %; ISFDNi = NDFi intake via supplement in g/day; FCFDNi = NDFi concentration in forage in %. To assess the performance, weights were measured at time zero (day 1) and then every 28 days (after 16 h of fasting from solids and liquids). Total weight gain (TWG) was determined by the difference between final and initial weight. The average daily gain (ADG) was calculated by dividing the TWG by the number of days of duration of the experiment for each period (LR and WS). 2.5. Rumen Degradability The rumen in situ bag technique was used to measure rumen degradability . The study design used 4 crossbred buffaloes with ruminal cannulae, and an initial age and average weight of 34 +- 04 months and 503 +- 48 kg, respectively, in a 4 x 4 Latin square experimental design (4 treatments with 4 repetitions) with repeated measures in time. Buffaloes were supplemented with the same levels of PKC and access to Marandu grass paddocks (Table 2). There were 4 periods of 25 days, with 21 days of adaptation of the animals to the diets and in situ incubation of the feed for a period of 4 days. The incubation times were: 0, 6, 12, 24, 48, 72 and 96 h, except for wheat bran, which was incubated for 48 h, with the bags placed in reverse order for removal at the same time. For the incubation of Marandu grass, the samples were dried and ground in a knife mill with a 5 mm sieve. PKC and wheat bran (WB) samples were ground to pass a 2 mm sieve . Degradability was determined by the "in situ" technique, using 100% polyamide-nylon unresined bags (14 x 7 cm), with approximately 50-micrometer pores, containing 5 g of sample, at a rate of 20 mg DM/cm2. After removal, the bags were washed in cold water to remove excess rumen content, immersed for 30 min in ice water to stop microbial activity and subsequently frozen. At the end of the process, all bags were washed in a washing machine (5 cycles of 10 min). Unincubated bags containing the same amounts of samples were washed along with incubated bags to represent the zero hours of incubation. After washing, the bags were dried in a forced ventilation oven (55 degC for 72 h). The percentage of DM, NDF, ADF and CP by incubation time was calculated by the difference between the incubated and the remainder in the samples, thus generating the degradation curves. The effects of treatments and incubation times on the dependent variables were evaluated using the model of : p = a + b (1 - e - ct), where p is the disappearance in time (t); a (fraction soluble); b (degradable fraction); c (rate of degradation of b); and t (time in hours). Effective degradability was estimated using the equation ED = a + [(b x c)/(c + k)], where ED is the effective degradability of nutrients; a (rapidly soluble fraction); b (potentially degradable fraction); c (rate of degradation of parameter b); and k (rate of passage of digestate out of the rumen), considered for rates of 0.02 h-1, 0.05 h-1 and 0.08 h-1 . Colonization time was estimated by the equation: CT = - (1/c) x {ln [(a + b - S)/b]}, where a, b and c are the same parameters as in the previous equation and S is the soluble fraction at time zero . In the fibrous fractions (NDF and ADF), the soluble fraction "S" was considered zero. The nonlinear parameters a, b and c were estimated by the algorithmic procedure of Gauss-Newton. 2.6. Statistical Analysis The data were analyzed by means of analysis of variance and regression, with the degrees of freedom broken down into linear or quadratic effects, the significance of up to 5%, using the PROC GLIMMIX of the Statistical Analysis System--SAS version 9.1 (SAS, 2009), according to the statistical model below:Yij = m + NLi + Eij where Yij = value observed in the plot that received treatment i in repetition j; m = overall average; NLi = fixed effect of oil palm inclusion level i (i = 0, 0.25, 0.5 and 1%); and Eij = random experimental error associated with each observation assumed NID ~ (0, s2). 3. Results 3.1. Voluntary Feed Intake Supplement intake (Kg/DM) increased linearly with the inclusion of palm kernel cake, reaching 5.57 and 5.31 kg at the highest inclusion level (WS and LR, respectively), but it was not influenced by season, nor was there any interaction (Table 3). Forage consumption (Kg/DM) was reduced with the inclusion of the co-product and was influenced by the change of season, also with a reduction in consumption; however, there was no interaction. The total DM intake was influenced only by the periods, with a reduction during the LR. Supplement consumption (%LW) was influenced only by treatments, reaching 0.9 kg in the treatment with 1% inclusion of palm kernel cake compared to 0.15 kg in the control treatment. On the other hand, forage consumption between treatments and seasons was reduced; however, without interaction. Total consumption was influenced only by the season, being higher in WS, with an average of 1.778 compared to 1.640 in LR. In relation to metabolic weight, all intakes were influenced by the inclusion of PKC (p < 0.05). However, only forage consumption was influenced by the season, with a linear reduction as well as an interaction. The consumption of CP, NDF, EE and NFC per kg of DM was influenced by the season, increasing in WS (p < 0.05). However, only the consumption of EE and NFC was influenced by the treatment, increasing and decreasing, respectively, with the highest levels of PKC inclusion (Table 4). The seasons also influenced the consumption of all fractions (% BW), being higher in WS (p < 0.05). The treatments only influenced the consumption of EE and NFC, with an increase (136.7%) and a decrease (33.5%), respectively. For feed consumption in relation to metabolic weight, the results followed the same pattern, influencing all fractions (CP, NDF, EE and NFC) with the change of season, being higher in WS, with the inclusion of the PKC supplement only influencing the intake of EE and NFC, with an increase and a decrease, respectively. The consumption of NFC reduced linearly in the two seasons and, in the comparison between the two, there was also a reduction (p < 0.05). In the WS, the reduction reached 25% and, in the LR, it reached 42.2%, between the 0% and 1.0% treatments (Table 5). 3.2. Degradability The inclusion of palm kernel cake in the diets influenced the in situ degradation of DM and NDF (p < 0.05), while the CP degradation equations and curves were similar (p > 0.05) (Table 6). The values of the coefficient of determination (R2) were greater than 92%, indicating a good fit of the data to the model equation . The degradation of palm kernel cake NDF was different at the TP0.25 level compared to the others (p < 0.05), and this level displayed atypical behavior, with a higher soluble fraction (8.66%) and higher TC (6:43 h). There was no difference in the degradation (DM) of Marandu grass (p > 0.05); however, the degradation of NDF and CP differed (p < 0.05) (Table 7). The NDF degradation equations for Marandu grass for the TP0 and TP1 treatments are different (p < 0.05), highlighting the values of the soluble fraction (A) (1.17 and 1.71, respectively), which may have contributed to the result of the kinetic parameters of the curves. For CP degradation, Marandu grass equations (PKC treatments) were different from the control treatment (TP0) (p < 0.05). Wheat bran DM and CP degradation were influenced by the inclusion of the palm kernel cake but there was no difference in NDF degradation (p > 0.05) (Table 8). Wheat bran DM ruminal degradation equations were similar in terms of kinetic behavior at supplementation levels TP0.5 and TP1 (p > 0.05); however, treatments TP0 and TP0.2 were different (p < 0.05). The colonization time of wheat bran was longer in the treatments with palm kernel cake, with a difference of 101 and 140 min between the 0% and 1% treatments for DM and CP, respectively. With respect to NDF, since the potentially degradable fraction was the same, and the degradation rates were similar, it can be inferred that the proposed PKC levels do not promote any effect on the degradability of wheat bran fiber. In the wheat bran CP degradation equations, there was an increase in the potentially degradable fraction, from 55.44% in TP0 to 89.99 in TP1. The highest effective degradability rates were observed in TP0 (86.41%, 79.04% and 73.60%) for the rates of 2%/h-1, 5%/h-1 and 8%/h-1, respectively, as well as the shortest colonization time (0:14 h). 3.3. Performance Palm kernel cake did not influence performance variables (p > 0.05) (Table 9). However, the average daily gain ranged from 0.478 to 0.544 kg in LR and from 0.211 to 0.339 kg in WS. The total average gain varied between 86 and 98 kg in the LR and, in the WS, from 26 to 62 kg. 4. Discussion 4.1. Feed Intake Concentrated feeds usually have high acceptability by animals, with consumption varying according to the ingredients used . Thus, the inclusion of PKC was a determining factor for the increase in supplement intake, regardless of the season. However, pasture supplementation tends to reduce forage consumption, as it promotes greater nutrient intake and, consequently, increases efficiency in the use of forage energy . Levels of supplementation greater than 0.3% of body weight/day significantly reduces the consumption of pasture grass . This fact contributes to animal performance and allows for more efficient use of available pastures and areas . The reduction in dry matter consumption (kg*day-1) can also be attributed to the inclusion of the supplement since it is a feed with greater nutritional density. Additionally, the presence of palm kernel cake in the diets increased the levels of ether extract, which was observed at the highest levels of PKC inclusion (TP0.5 and TP1), which can cause a reduction in fiber digestibility (Table 4). The greater consumption of WS compared to LR provided a greater intake of the NDF, EE and NFC fractions per kg of DM, body weight and metabolic rate. The increase in EE consumption and reduction in NFC intake reflects the change caused by palm kernel cake in the nutritional composition of the diet. This co-product is high in fat and ADF but low in NFC, thus directly influencing the intake of these fractions (Table 2) . The lower values found in the LR season are probably a reflection of the lower DM consumption (Table 3). For digestible energy, the reduction possibly occurred by replacing pasture with concentrate, since there was a reduction in roughage consumption with supplementation, resulting in an increase in digestible energy intake. 4.2. Degradability Palm kernel cake, despite its good nutritional composition in protein and energy, raises ADF and lignin levels, promoting changes in the digestive process, such as longer degradation time, microorganism action and passage rate . These changes may reflect reduced intake, digestibility, and animal performance . The influence on fiber degradation, in turn, may have occurred due to the higher consumption of EE by animals (TP1), since the addition of lipids in ruminant diets may have this effect . Furthermore, the limitation in the degradation of palm kernel cake is due to the indigestible fraction associated with the endocarp residues present in this ingredient, a highly lignified and extremely hard tissue . Ruminal degradability and digestibility are key measures to consider when determining the nutritive value of new ingredients . As the potentially degradable fraction was the same and the degradation rates were similar, it can be inferred that, regardless of the TP level, there was no effect on wheat bran fiber degradability . The differences in the Marandu grass CP degradation equations may be due to the average increase in TC of 1:37h between the TP0 levels and the treatments with the inclusion of palm kernel cake. The effect of PKC on the degradation equations also possibly reflects the increase in the ADF and lignin fractions present in the co-product. Lignin, in addition to being indigestible, can make it impossible to digest other fractions, limiting access by microorganisms and causing longer colonization times. This may have occurred, for example, in the protein equations, where there was an average increase in TC of 107 min between the most distant levels. The influence on wheat bran degradation was probably due to the composition of the palm kernel cake and the changes caused in the rumen environment and digestive processes, such as the increase in colonization time for fiber degradation and the increase in fat. 4.3. Performance The equality observed in the results demonstrates that, despite the variations in consumption and nutritional components, the inclusion of the co-product provides an equivalent performance of the animals, as already observed in goats and cattle . Adequate pasture management conditions, with an average supply of 8 kg of DM/100 kg of BW, above the minimum requirement required by buffaloes for good productive performance, which is 1200 to 1600 kg of DM ha-1 , and supplementation with PKC may have contributed to the equality in the performance of the animals. 5. Conclusions Supplementation of buffaloes with palm kernel cake reduces forage consumption, thus reducing the necessity of increasing pasture area, and it influences diet degradability but does not interfere with performance. More studies are recommended to improve the use of this co-product as part of a sustainable feeding management strategy. Acknowledgments Embrapa Eastern Amazon, PECUS Network and collaborators from the Animal Research unit; Marborges Agroindustria S.A. by donating the co-product; Coordination for the Improvement of Higher Education Personnel (CAPES) and Dean of Research and Graduate Studies (PRO-PESP/UFPA). Author Contributions Conceptualization, J.M.d.A.-J., E.d.M. and A.C.S.L.; methodology, J.M.d.A.-J., A.C.S.L., L.F.S. and A.L.d.C.S.; software, L.G.M. and B.d.S.N.; validation, A.G.M.e.S., A.L.d.C.S., J.d.B.L.-J. and J.A.R.d.S.; formal analysis, J.M.d.A.-J., E.d.M., A.G.M.e.S. and J.d.B.L.-J.; investigation, J.M.d.A.-J., A.C.S.L., L.G.M., B.d.S.N., T.C.G.d.C.R. and A.L.d.C.S.; resources, J.M.d.A.-J., A.G.M.e.S., J.d.B.L.-J. and A.L.d.C.S.; data curation, J.M.d.A.-J. and A.G.M.e.S.; writing--preparation of the original draft, J.M.d.A.-J., T.C.G.d.C.R. and J.A.R.d.S.; writing--proofreading and editing, all authors; visualization, A.G.M.e.S.; supervision, J.M.d.A.-J., A.L.d.C.S., J.d.B.L.-J., A.C.S.L. and L.F.S.; project management, A.G.M.e.S., J.d.B.L.-J., L.G.M., B.d.S.N. and A.L.d.C.S.; acquisition of financing, A.G.M.e.S., J.d.B.L.-J., A.L.d.C.S., L.G.M. and B.d.S.N. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement All procedures with the animals were performed with authorization from the Ethics Committee on the Use of Animals of Embrapa/Eastern Amazon, under protocol No. 007/2015. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available on request from the corresponding author. Conflicts of Interest The authors Benjamin de Souza Nahum and Lucieta Guerreiro Martorano are employed by EMBRAPA (Brazilian Agricultural Research Corporation). They and other authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. animals-13-00934-t001_Table 1 Table 1 Chemical composition of the ingredients of the experimental diets. Items PKC WB MG LR 1 WS 2 LR WS LR WS DM 3% 90.47 89.30 88.32 89.70 31.10 27.90 CP 4 (%DM) 11.12 13.40 15.49 16.28 8.19 8.84 NDFcp 5 (%DM) 69.87 59.90 44.19 42.61 68.14 67.19 ADFcp 6 (%DM) 48.23 31.40 14.27 13.21 40.55 38.21 Ash (%DM) 4.61 4.26 5.88 5.03 6.76 6.44 EE 7 (%DM) 11.64 13.19 3.48 3.19 2.54 2.63 NFC 8 (%DM) 2.76 9.25 30.96 32.89 14.37 14.90 PKC = Palm kernel cake; WB = wheat bran; MG = Marandu grass; 1 Less rainy period (July to December); 2 Wettest period (January to June); 3 DM = dry matter; 4 CP = crude protein; 5 NDFcp = neutral detergent fiber corrected for ash and protein; 6 ADFcp = fiber in acid-detergent corrected for ash and protein; 7 EE = ether extract; 8 NFC = non-fibrous carbohydrates. animals-13-00934-t002_Table 2 Table 2 Chemical composition of the diets with the inclusion of palm kernel cake supplement based on dry matter. Items Supplement Treatments PKC 0 PKC 0.2 PKC 0.5 PKC 1 DM 1 (g/kg supplement) 883.2 883.0 899.0 902.0 CP 2 (g/kg DM) 154.9 127.0 121.0 117.0 NDFcp 3 (g/kg DM) 441.9 602.0 640.0 666.0 ADFcp 4 (g/kg DM) 142.7 355.0 405.0 439.0 Ash (g/kg DM) 58.8 50.8 48.9 47.7 EE 5 (g/kg DM) 34.8 85.8 97.9 106.0 NFC 6 (g/kg DM) 309.6 133.0 91.4 63.6 1 Dry matter; 2 Crude protein; 3 Neutral detergent fiber corrected for ash and protein; 4 Fiber in acid-detergent corrected for ash and protein; 5 Ether extract; 6 Non-fibrous carbohydrates. animals-13-00934-t003_Table 3 Table 3 Supplement, Marandu forage, and total feed intake by buffaloes in two seasons in the eastern Amazon. Period Inclusion PKC (% BW) Average 1 CV DMS SEM 3 p-Value 0.0 0.25 0.50 1.0 G p G x p Average supplement consumption (kg of DM) WS 4 0.98 d 2.56 c 4.15 b 5.57 a 3.31 A 10.8 0.406 0.142 <0.01 0.08 0.89 LR 5 0.91 d 2.40 c 3.93 b 5.31 a 3.14 A Average 2 0.94 d 2.48 c 4.04 b 5.44 a 0.287 0.100 Average forage consumption (kg of DM) WS 11.12 a 7.97 b 7.07 b 5.73 c 7.98 A 11.2 0.958 0.335 <0.01 <0.01 0.37 LR 9.17 a 7.15 b 5.97 c 4.27 d 6.64 B Average 10.15 a 7.56 b 6.52 c 4.99 d 0.677 0.237 Average of total consumption (kg of DM) WS 12.10 10.52 11.22 11.3 11.28 A 9.3 1.147 0.401 0.087 <0.01 0.58 LR 10.08 9.56 9.902 9.57 9.780 B Average 11.09 10.04 10.56 10.43 0.811 0.283 Supplement consumption (% LW) WS 0.15 d 0.400 c 0.650 b 0.900 a 0.525 A 1.7 0.010 0.003 <0.01 0.41 0.57 LR 0.15 d 0.400 c 0.650 b 0.908 a 0.527 A Average 0.15 d 0.400 c 0.650 b 0.904 a 0.007 0.002 Forage consumption (% LW) WS 1.726 a 1.247 b 1.109 bc 0.931 c 1.253 A 13.3 0.184 0.064 <0.01 <0.01 0.65 LR 1.533 a 1.195 b 0.987 c 0.738 d 1.113 B Average 1.629 a 1.221 b 1.048 c 0.834 d 0.130 0.045 Total consumption (% LW) WS 1.876 1.647 1.759 1.831 1.778 A 9.13 0.182 0.063 0.09 <0.01 0.66 LR 1.683 1.595 1.637 1.646 1.640 B Average 1.779 1.621 1.698 1.738 0.128 0.045 Supplement consumption (BW0.75) WS 0.042 d 0.113 c 0.183 b 0.252 a 0.147 A 3.53 0.003 0.001 <0.01 0.28 0.97 LR 0.041 d 0.111 c 0.181 b 0.250 a 0.146 A Average 0.042 d 0.112 c 0.182 b 0.251 a 0.004 0.001 Forage consumption (BW0.75) WS 259.6 aA 89.09 bA 54.95 cA 34.89 dA 109.6 A 9.0 10.59 3.706 <0.01 <0.01 <0.01 LR 214.0 aB 79.99 bA 46.40 cA 25.80 dA 91.56 B Average 236.8 a 84.54 b 50.68 c 30.34 d 7.490 2.620 Total Consumption (BW0.75) WS 45.47 c 50.20 c 58.59 b 67.64 a 55.48 A 11.1 7.03 2.459 <0.01 0.25 0.78 LR 41.67 c 47.20 c 56.34 b 68.58 a 53.45 A Average 43.57 d 48.70 c 57.46 b 68.11 a 4.97 1.73 1 Average of the period; 2 Average of treatment; 3 Standard error of the mean; 4 the wettest season; 5 the less rainy season; LW = live weight; BW = body weight; G = Treatment; p = Period; Equal lowercase letters in the same row means no significant difference. Different lowercase letters in the same row indicate a significant difference. Equal capital letters in the same column mean no significant difference. Different capital letters in the same column indicate a significant difference. animals-13-00934-t004_Table 4 Table 4 Chemical analysis of consumption as a function of increasing levels of palm kernel cake by buffaloes in two seasons in the eastern Amazon. Items Inclusion PKC Periods Effects R2 SEM 0.0 0.25 0.5 1.0 LR WS TREAT PER TREAT*PER Consumption (kg of DM) CP 1.017 0.981 1.085 1.120 0.929 B 1.172 A NS * NS - 0.005 NDF 7.266 6.516 6.824 6.747 6.498 B 7.179 A NS * NS - 0.045 EE 0.293 d 0.418 c 0.587 b 0.72 a 0.464 B 0.546 A * * NS 96.01 0.019 NFC 1.785 a 1.496 b 1.436 b 1.240 c 1.274 B 1.705 A * * NS 90.12 0.058 Consumption (% BW) CP 0.169 0.159 0.176 0.179 0.157 B 0.185 A NS * NS - 0.011 NDF 1.213 1.058 1.113 1.085 1.097 B 1.137 A NS * NS - 0.074 EE 0.049 d 0.067 c 0.095 b 0.116 a 0.078 B 0.086 A * * NS 95.74 0.006 NFC 0.298 a 0.242 b 0.233 b 0.20 b 0.215 B 0.270 A * * NS 88.44 0.015 Consumption (BW0.75) CP 8.394 7.928 8.784 8.971 7.738 B 9.301 A NS * NS - 0.498 NDF 59.999 52.695 55.34 54.12 54.09 B 56.983 A NS * NS - 3.230 EE 2.425 d 3.382 c 4.756 b 5.81 a 3.862 B 4.322 A * * NS 95.79 0.259 NFC 14.743 a 12.08 b 11.61 bc 9.89 c 10.62 B 13.545 A * * * 88.92 0.690 * Significant effect (p < 0.05); NS--not significant (p > 0.05) Student's t-test; Means in the same row followed by different uppercase and lowercase letters, respectively, differ from each other (p < 0.05) by Tukey's test; LR--the less rainy season; WS--the wettest season; R2 = determination coefficient; SEM--standard error of the mean; CP = Crude protein; NDF = neutral detergent fiber; EE = ether extract-y = 0.32 + 0.43x, y = 0.05 + 0.07x, y = 2.60 + 3.41x; NFC = non fiber nitrogen-y = 1.71 - 0.50x, y = 0.283 - 0.091x, y = 14.02 - 4.43x. animals-13-00934-t005_Table 5 Table 5 Intake of non-fiber carbohydrates under the effect of interaction between treatment and period in buffaloes in the Amazon eastern. Period Inclusion PKC p 1 R2 SEM 2 0 0.25 0.5 1.0 WS 3 16.0 aA 13.1 bA 13.1 bA 12.0 bA * 73.6 0.506 LR 4 13.5 aB 11.1 bB 10.1 bB 7.8 cB * 96.2 0.506 p * * * * 1p-value; 2 Standard error of the mean; 3 Rainiest season; 4 Less rainy season; R2 = determination coefficient; * Significant effect (p < 0.05); Means in the same row followed by different uppercase and lowercase letters, respectively, are significant (p < 0.05) by Tukey's test; Equations: WS-y = 15.07 - 3.47x; LR-y = 12.99 - 5.41x. animals-13-00934-t006_Table 6 Table 6 Equations for ruminal degradation, colonization time (CT) and effective degradability (ED) of dry matter (DM), fiber in neutral detergent (NDF) and crude protein (CP) of palm kernel cake by buffaloes in the eastern Amazon. Items Equations 1 R2 % CT (h:min) ED (2%/h) % ED (5%/h) % ED (8%/h) % Dry Matter TP0 p = 26.28 + 52.11 (1 - exp-0.0709t) A 97.70 3:54 50.30 39.06 35.96 TP0.2 p = 27.08 + 52.97 (1 - exp-0.0596t) A 96.10 4:46 50.59 39.10 35.89 TP0.5 p = 26.32 + 60.42 (1 - exp-0.0367t) A 97.30 6:39 50.85 39.29 35.14 TP1 p = 22.87 + 52.77 (1 - exp-0.0316t) B 98.60 7:04 50.98 39.79 34.09 Fiber in Neutral Detergent TP0 p = 6.31 + 72.06 (1 - exp-0.0227t) B 98.20 3:40 44.68 28.86 22.28 TP0.2 p = 8.66 + 84.38 (1 - exp-0.0145t) A 92.00 6:43 44.12 27.63 21.60 TP0.5 p = 6.23 + 70.97 (1 - exp-0.0236t) B 98.30 3:33 44.68 29.01 22.42 TP1 p = 5.61 + 75.08 (1 - exp-0.0220t) B 97.80 3:16 44.97 28.57 21.82 Crude Protein TP0 p = 39.05 + 60.12 (1 - exp-0.0193t) A 98.10 1:20 68.58 55.80 50.74 TP0.2 p = 36.82 + 64.30 (1 - exp-0.0196t) A 98.40 0:30 68.72 54.99 49.52 TP0.5 p = 26.32 + 60.42 (1 - exp-0.0367t) A 98.30 0:15 69.14 55.14 49.78 TP1 p = 22.87 + 52.77 (1 - exp-0.0316t) A 98.40 0:03 69.69 56.03 50.92 1 Orskov and McDonald's model (1979). p = Amount of substrate degraded in time (t); CT = Colonization time; R2 = determination coefficient; ED = Effective degradability; Equations accompanied by the same capital letters in the same column are identical by the parameter identity test at 5% probability of type I error . The highest supplementation level (PKC1) differed from the others in the behavior and distance from the DM degradation curves of palm kernel cake (p < 0.05). animals-13-00934-t007_Table 7 Table 7 Equations for ruminal degradation, colonization time (CT), effective degradability (ED) of dry matter (DM), fiber in neutral detergent (NDF) and crude protein (CP) of Marandu grass as a function of increasing levels of palm kernel cake for buffaloes in the eastern Amazon. Items Equations 1 R2 % CT (h:min) ED (2%/h) % ED (5%/h) % ED (8%/h) % Dry matter TP0 p = 16.64 + 73.96 (1 - exp-0.0265t) A 99.40 02:30 50.83 35.93 29.31 TP0.2 p = 17.43 + 71.66 (1 - exp-0.0273t) A 99.60 02:27 50.76 35.42 30.22 TP0.5 p = 18.60 + 82.04 (1 - exp-0.0226t) A 98.90 02:07 50.44 35.20 29.83 TP1 p = 16.20 + 77.93 (1 - exp-0.0254t) A 99.60 01:09 50.16 34.59 28.81 Fiber in neutral detergent TP0 p = 1.17 + 79.23 (1 - exp-0.0230t) B 99.20 00:37 43.62 26.20 18.91 TP0.2 p = 1.64 + 78.76 (1 - exp-0.0238t) AB 99.30 00:41 44.45 26.05 19.70 TP0.5 p = 1.48 + 81.01 (1 - exp-0.0243t) AB 99.20 00:48 44.21 26.49 19.15 TP1.0 p = 1.71 + 78.35 (1 - exp-0.0258t) A 99.50 00:51 45.15 27.75 20.30 Crude Protein TP0 p = 39.89 + 28.64 (1 - exp-0.0518t) B 97.10 00:40 60.56 54.47 51.15 TP0.2 p = 37.04 + 30.73 (1 - exp-0.0570t) A 97.30 02:08 59.85 53.49 49.90 TP0.5 p = 36.22 + 30.88 (1 - exp-0.0575t) A 97.70 02:18 59.57 52.74 48.91 TP1.0 p = 37.15 + 30.80 (1 - exp-0.0605t) A 95.90 02:27 60.31 54.03 50.42 1 Orskov and McDonald's Model (1979). p = Amount of substrate degraded in time (t); R2 = determination coefficient; CT = Colonization time; ED = Effective Degradability. The groups TP0.00; TP0.25; TP0.50 and TP1.00 correspond to treatments of 0.0%, 0.25%, 0.50% and 1.0% of palm kernel cake in relation to the BW of the buffaloes; Equations accompanied by equal capital letters in the same column are identical by the parameter identity test at 5% probability of type I error . animals-13-00934-t008_Table 8 Table 8 Equations of ruminal degradation, colonization time (CT), effective degradability (ED) of dry matter (DM), neutral detergent fiber (NDF) and crude protein (CP) of wheat bran as a function of increasing levels of palm kernel cake for buffaloes in the eastern Amazon. Items Equations 1 R2 % CT (h:min) ED (2%/h) % ED (5%/h) % ED (8%/h) % Dry Matter TP0 p = 48.77 + 30.31 (1 - exp-0.0886t) C 97.60 0:28 73.50 68.15 64.70 TP0.2 p = 57.19 + 23.84 (1 - exp-0.0368t) B 97.40 2:00 72.64 67.30 64.70 TP0.5 p = 59.62 + 24.85 (1 - exp-0.0358t) A 82.10 2:09 75.57 70.00 67.31 TP1 p = 59.90 + 23.18 (1 - exp-0.0380t) A 92.90 2:09 75.10 69.92 67.37 Neutral detergent fiber TP0 p = 1.32 + 89.99 (1 - exp-0.0492t) A 99.00 0:17 65.33 45.99 35.62 TP0.2 p = 1.85 + 89.98 (1 - exp-0.0452t) A 98.70 0:27 64.24 44.58 34.35 TP0.5 p = 1.12 + 89.99 (1 - exp-0.0487t) A 99.30 0:15 64.92 45.53 35.18 TP1 p = 1.96 + 89.99 (1 - exp-0.0484t) A 99.30 0:26 65.65 46.24 35.90 Crude Protein TP0 p = 37.54 + 55.44 (1 - exp-0.1488t) A 98.30 0:14 86.41 79.04 73.60 TP0.2 p = 27.19 + 64.46 (1 - exp-0.1991t) B 98.40 1:03 85.78 78.72 73.19 TP0.5 p = 17.18 + 74.82 (1 - exp-0.1898t) C 98.50 1:52 84.91 76.44 69.85 TP1 p = 21.95 + 89.99 (1 - exp-0.2088t) D 98.40 2:34 84.09 74.57 67.03 1 Orskov and McDonald's Model (1979). p = Amount of substrate degraded in time (t); R2 = determination coefficient; CT = Colonization time; ED = Effective Degradability. The groups TP0.00; TP0.25; TP0.50 and TP1.00 correspond to the treatments 0.0%, 0.25%, 0.50% and 1.0% of palm kernel cake in relation to the BW of the buffaloes; Equations accompanied by equal capital letters in the same column are identical by the parameter identity test at 5% probability of type I error . animals-13-00934-t009_Table 9 Table 9 Performance of female buffaloes under intermittent grazing of Marandu grass supplemented with different levels of palm kernel cake. Variables Treatments R2 SEM 1 CV 2 p TP0 TP0.25 TP0.5 TP1 LR 7 IW 3 (Kg) 508.0 494.0 502.0 508.0 - 57.27 0.11 0.94 FW 4 (Kg) 606.0 580.0 595.0 596.0 - 48.66 0.08 0.89 TAG 5 (Kg) 98.0 86.0 93.0 88.0 - 19.40 0.21 0.57 ADG 6 (Kg) 0.544 0.478 0.517 0.489 - 0.11 0.21 0.57 WS 8 IW (Kg) 612.0 604.0 603.0 601.0 - 57.01 0.09 0.76 FW (Kg) 673.0 656.0 629.0 639.0 - 56.72 0.09 0.29 TAG (Kg) 61.00 52.0 26.0 38.0 - 27.19 0.61 0.12 ADG (Kg) 0.339 0.289 0.144 0.211 - 0.15 0.61 0.12 1 Standard error of the mean; 2 Coefficient of variation; 3 Initial weight; 4 Final weight; 5 Total average gain (180 days); 6 ADG = Average daily gain; 7 Less rainy season; 8 Wetter season; R2 = determination coefficient; p = p-value. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000220 | In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (<=0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was <=12 months, or the Gleason score was >=7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p <= 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology. prostate cancer biochemical recurrence low serum prostate-specific antigen (PSA) concentration gallium-68 prostate-specific membrane antigen-11 positron emission tomography (68Ga-PSMA-11 PET/CT) detection rate PSA doubling time Gleason score This research received no external funding. pmc1. Introduction Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein that is overexpressed on the surface of malignant prostate cells , has rapidly emerged as an important target in imaging and treating this neoplasm . In men with biochemical recurrence of prostate cancer (BCR), positron emission tomography/computed tomography (PET/CT) with radiotracers built on PSMA ligands is gaining growing use to try to localize tumor as accurately and early as possible, thereby attempting to optimize salvage therapy. As with PET/CT using other PSMA-targeted radiotracers , the detection rate with gallium-68 (68Ga)-PSMA-11 PET/CT of lesions suspicious for prostate cancer is well known to rise along with PSA concentration . However, published data are relatively sparse regarding this imaging modality's performance in men with BCR and very low (ultrasensitive) PSA concentrations, i.e., <=0.2 ng/mL. To our knowledge, the literature regarding 68Ga-PSMA-11 PET/CT detection rates with this setting contains only two studies, including >100 patients with such very low PSA levels (those of Afshar-Oromieh et al. and Meredith et al. ); additional reports covering this topic, e.g., , have involved much smaller samples. Because the increasing use of PSMA-targeted PET/CT in prostate cancer is likely to be associated with greater use in earlier stages of BCR, it is important to characterize further 68Ga-PSMA-11 PET/CT performance in the very low PSA BCR setting. We, therefore, conducted the present analysis of our ~7-year "real-world" experience in a large dual-center cohort. 2. Patients and Methods 2.1. Study Design, Patients, and Endpoints This was a retrospective analysis of 68Ga-PSMA-11 PET/CT findings in 115 consecutive men with a history of radical prostatectomy and with BCR marked by increasing but very low PSA concentration (<=0.2 ng/mL), as determined by local laboratories. Patients were referred by their treating urologist. Scanning took place between 15 January 2015 and 28 September 2022 at the outpatient nuclear medicine clinics of either of two German academic institutions, the Saarland University Medical Center, Homburg (n = 70, 60.9%) or the Johannes Gutenberg-University Medical Center, Mainz (n = 45, 39.1%). The analysis had two main inclusion criteria. First, patients' PSA concentrations had to be > 0 to <= 0.2 ng/mL. Second, patients had to have 68Ga-PSMA-11 PET/CT undertaken to seek structural correlates of PSA increase following primary treatment with radical prostatectomy. Cohort characteristics are summarized in Table 1. The study sample tended to be in late middle age, and almost all had either an intermediate-risk (Gleason score = 7) or high-risk (Gleason score >= 8) histology of surgical samples (data available from 107/115 patients). At the time of scanning, the PSA concentration was <0.1 ng/mL, 0.1-0.15 ng/mL, or >0.15-0.2 ng/mL in about one-third of patients each. PSA doubling time was <=12 months in more than four-fifths of patients with available data regarding this variable (n = 83/115; in the remaining patients, doubling time could not be calculated due to missing data regarding earlier PSA measurements). Only a small minority (<10% for either intervention) had received radiation or androgen deprivation therapy in addition to radical prostatectomy. The primary endpoint of the analysis was the per-patient visual detection rate (positive scans/total scans) of any lesion(s) suspicious for prostate cancer. Secondary endpoints included the detection rate by lesion type (categorized as putative local recurrence, putative lymph node metastasis, or putative bone metastasis) and by PSA concentration, PSA doubling time, and Gleason score. Additional secondary endpoints included maximum standardized uptake values (SUVmax) for suspicious lesions overall and by type. The analysis was conducted according to the Declaration of Helsinki and approved by the Institutional Review Board of the Arztekammer des Saarlandes/Saarbrucken (approval number: 170/22, approval date: 13 September 2022) and the ethics committee of the Medical Association Rhineland-Palatinate (Laek Rlp) (approval number: 2018/13390, approval date: 29 October 2018). All patients provided written informed consent for the 68Ga-PSMA-11 PET/CT and for the use of their de-identified data for scientific analyses and publications. 2.2. 68Ga-PSMA-11 PET/CT All patients underwent whole-body scanning on 68Ga-PSMA-11 PET/CT ~60 min after intravenous injection (mean activity 157.8 +- 51.2 MBq) of the tracer followed by 0.9% NaCl, 500 mL; they were encouraged to void between the time of injection and that of data acquisition. PET/CT scans were performed on a Biograph 40 mCT PET/CT scanner (Siemens Healthineers, Erlangen, Germany; Homburg) or on a Gemini TF16 PET/CT scanner (Philips Medical Systems, Best, Netherlands; Mainz). The matrix was 200 x 200 (Homburg) or 168 x 168 (Mainz), the acquisition time was 3 min/bed position, the extended field-of-view was 21.4 cm (TrueV) (Homburg) or 18.0 cm (Mainz), and the slice thickness was 3.0 mm (Homburg) or 4.0 mm (Mainz). PET reconstruction was performed iteratively using a three-dimensional ordered-subset expectation maximization algorithm with three (Homburg) or two (Mainz) iterations, 24 (Homburg) or 33 (Mainz) subsets, Gaussian filtering, and 5.0 mm (Homburg) or 4.2 mm (Mainz) transaxial resolution at full-width at half maximum. CT was acquired for attenuation correction and anatomical localization using a low-dose scan. Aside from attenuation correction, decay correction, random correction, and scatter correction were performed. At each center, the PET/CT images were visually assessed by consensus of two board-certified nuclear medicine specialists, both of whom had extensive experience in interpreting 68Ga-PSMA-11 PET/CT images. 68Ga-PSMA-11 was produced in-house using PSMA-11 supplied by ABX advanced biochemical compounds GmbH (Radeberg, Germany) and 68Ga from a 68-germanium/68Ga generator (Eckert & Ziegler Medizintechnik AG, Berlin, Germany). The synthesis of 68Ga-PSMA-11 was performed according to published procedures . Quality control of the final product followed the rules of Good Manufacturing Practice (cGMP) guidelines. Radiopharmaceutical purity of >98% was required and tested by HPLC and iTLC. 2.3. Statistics Data on patient and imaging characteristics and scan findings are reported as descriptive statistics, as applicable. Statistical tests were performed on Prism version 8 (GraphPad Software, San Diego, CA, USA). p values < 0.05 were deemed to be statistically significant. The chi-square test was used to compare overall suspicious lesion detection rates among PSA, PSA doubling time, and Gleason score subgroups as well as between study centers. Differences in SUV depending on lesion category were compared using the Mann-Whitney U test. 3. Results Overall, 29/115 patients (25.2%) have lesions suspicious of prostate cancer on 68Ga-PSMA-11 (Table 2). The positive scans show 44 suspicious lesions altogether (median [minimum-maximum] 1 [1-4] per patient with positive scan). These include 11 putative local recurrences, 22 putative lymph node metastases, and 11 putative bone metastases. No lesions suspicious of visceral metastasis are detected. The lowest PSA value is 0.02 ng/mL for a positive scan and 0.03 ng/mL each for a scan with >=2 suspicious lesions (9/115, 7.8%). Representative images of positive scans are seen in Figure 1, and the specific anatomic sites of all detected lesions are depicted in Figure 2A. The SUVmax is similar (p = 0.87) between putative local recurrences and presumed lymph node metastases. However, the SUVmax is significantly lower (p < 0.01) for bone metastases than for the other two lesion classifications . Figure 3 illustrates overall detection rates according to categories of PSA concentration. The PSA detection rates are 21.1% (8/38 patients), 18.9% (7/37 patients), and 35.0% (14/40 patients) for PSA levels < 0.1 ng/mL, 0.1-0.15 ng/mL and >0.15 ng/mL, respectively. The rate is markedly higher in patients with PSA > 0.15 ng/mL than in their counterparts with lesser PSA concentrations, but the difference only shows a possible trend toward statistical significance (p = 0.07). Figure 1 Representative 68Ga-PSMA-11 PET/CT transversal slice PET images (upper right-hand scans) and PET/CT fusion images (left-hand and lower right-hand scans) of suspicious lesions: (A) putative local recurrence in a 71-year-old man with a PSA concentration of 0.10 ng/mL and (B) a putative left iliac lymph node metastasis in a 67-year-old man with a PSA concentration of 0.13 ng/mL. Figure 2 Characteristics of lesions suspicious for prostate cancer on 68Ga-PSMA-11 PET/CT in men with BCR and very low PSA concentration (N = 115). (A) Anatomic location and putative category of lesions (n = 44). Dots represent a single lesion and are color-coded as to putative category. (B) Descriptive statistics of SUVmax by suspicious lesion category. SUVmax does not differ (p = 0.87) between presumed local recurrences (n = 11) and lymph node metastases (n = 22) but is significantly lower (p < 0.01) for putative bone metastases (n = 11) than for the other lesion categories. Figure 3 Detection rate on 68Ga-PSMA-PET/CT of lesions suspicious for prostate cancer by PSA level subgroup in 115 men with BCR and very low serum PSA concentration. Panel A depicts the numbers of patients with scans positive or negative for suspicious lesions, while Panel B provides detection rates in percent (numbers atop the bars). Patients with PSA > 0.15-0.2 ng/mL have a substantially higher detection rate than their counterparts with PSA <= 0.15 ng/mL, but the difference does not reach statistical significance (p = 0.07). cancers-15-01376-t002_Table 2 Table 2 68Ga-PSMA-11 PET/CT findings in 115 men with BCR and very low PSA concentration. Variable Value Overall scan classification, % (n) Positive 25.2% (29) Negative 74.8% (86) Suspicious lesions on positive scans Total 44 Median (minimum-maximum) 1 (1-4) Number of lesions/positive scan, % (n) 1 69% (20/29) 2 14% (4/29) 3 14% (4/29) 4 3% (1/29) Type of lesions, % (n) Local recurrence 25% (11/44) Lymph node metastasis 50% (22/44) Bone metastasis 25% (11/44) Types of lesions on a positive scan, % (n) Local recurrence only 24% (7/29) Lymph node metastasis only 34% (10/29) Bone metastasis only 24% (7/29) Local recurrence + lymph node metastasis 10% (3/29) Local recurrence + bone metastasis 3% (1/29) Lymph node metastasis + bone metastasis 3% (1/29) SUVmax of suspicious lesions All suspicious lesions Median (minimum-maximum) 5.3 (2.1-26.3) Mean +- SD 7.2 +- 5.3 Local recurrence Median (minimum-maximum) 5.7 (2.5-19.4) Mean +- SD 8.2 +- 5.6 Lymph node metastasis Median (minimum-maximum) 6.6 (2.1-26.3) Mean +- SD 8.3 +- 5.8 Bone metastasis Median (minimum-maximum) 3.3 (2.3-7.7) Mean +- SD 3.9 +- 1.5 Percentages represent proportions of the overall study sample or the subgroup with available data regarding a variable, as applicable. Due to rounding, not all percentages may add up to exactly 100%. Abbreviations: 68Ga, gallium-68; PSMA, prostate-specific membrane antigen; SD, standard deviation; and SUVmax, maximum standardized uptake value. a Lesion classifications are putative and not biopsy-confirmed. Figure 4 shows overall detection rates according to PSA doubling time categories (n = 83) (Panels A-B) and Gleason score categories (n = 107) (Panels C-D). Scan positivity is significantly higher (p = 0.04) among men with doubling times <= 12 months than among those with slower doubling times. Indeed, only 1/16 patients (6%) in the latter subgroup have positive 68Ga-PSMA-11 PET/CT. The overall suspicious lesion detection rate is also significantly higher (p = 0.01) in men with Gleason scores >= 7b than in patients with lower Gleason scores. Of note, there is no significant difference in the positivity rate between the study centers (p = 0.24). Figure 4 Rate of detection on 68Ga-PSMA-11 PET/CT of lesions suspicious for prostate cancer in 115 men with BCR and very low PSA concentration (A,B) by PSA doubling time category (in months) (n = 83) and (C,D) by Gleason score of surgical specimen (n = 107). Panels (A,C) show numbers of patients with positive or negative scans, while panels (B,D) depict the overall suspicious lesion detection rate in percent (numbers atop the bars). Detection rates are significantly higher (p = 0.04) in patients with doubling time < 12 months (n = 67) than in their counterparts with doubling time > 12 months (n = 16). Additionally, detection rates are significantly higher (p = 0.01) in men with a Gleason score >= 7b (n = 62) than in those with a Gleason score of 6 or 7a (n = 45). 4. Discussion The present analysis provides, from everyday practice over a long term in a large cohort, further evidence of the value of 68Ga-PSMA-11 PET/CT in localizing lesions suspicious for prostate cancer in prostatectomized patients with BCR but very low PSA levels. All of our patients have PSA concentrations at or below the European Association of Urology threshold to define BCR, 0.2 ng/mL , which is also the recommended level above PSMA where PET/CT should be performed, according to the current joint SNM and EANM guideline . Notwithstanding those ultrasensitive PSA values and notwithstanding the well-established PSA concentration-dependence of 68Ga-PSMA-11 PET/CT , our per-patient scan positivity rate is 25.2% (29/115) by visual assessment. Our findings include multiple cases of one or more of not only putative local (prostate bed) recurrence but presumed lymph node and/or bone metastasis. Of interest, scan positivity is noted at PSA levels as low as 0.02 ng/mL and putative oligometastasis and/or bone metastasis at levels as low as 0.03 ng/mL. These detection rates are broadly in line with the 33% pooled rate reported for 68Ga-PSMA-11 PET/CT in 197 prostatectomized patients with PSA <= 0.19 ng/mL in the meta-analysis of Perera et al. but are substantially lower compared with the 43.4% detection rate (98/226) reported by Afshar-Oromieh et al. in the largest published cohort of prostatectomized men with PSA <= 0.2 ng/mL. In contrast, our scan positivity rates in the very low PSA BCR setting were a bit over twice those of Meredith et al. in patients with PSA < 0.2 ng/mL, 11.3% (14/124). This discrepancy may be attributable to those investigators using a rather strict requirement for positivity, i.e., focal 68Ga-PSMA-11 uptake had to correspond with suspicious CT findings that we did not apply. Unsurprisingly, the detection rate in our cohort is lower than those reported elsewhere in patients with higher PSA concentrations, e.g., 46% for 0.2-0.49 ng/mL, 57% for 0.5-0.99 ng/mL, 82% for 1-1.99 ng/mL, and 97% for >=2 ng/mL in the Perera et al. meta-analysis . However, analogous PSA concentration dependence of detection rates also appears to manifest within the very low PSA setting in our study. Scan positivity occurs 66% and 85% more frequently in our patients with PSA > 0.15 ng/mL than in their counterparts with PSA < 0.1 ng/mL or 0.1-0.15 ng/mL, respectively, albeit these differences approach but do not reach statistical significance (p = 0.07). This p-value was perhaps due to the relatively small size of the subgroups. In our cohort, faster PSA doubling time and higher Gleason scores were associated with a higher rate of scan positivity. Comparable observations regarding the Gleason score appear in the literature . Localization of prostate cancer recurrence may be expected to allow the selection of potentially less toxic and more effective fields and doses of radiation therapy. Such imaging results also could facilitate promising metastasis-directed approaches in cases of oligometastatic disease. Given these potential benefits related to 68Ga-PSMA-11 PET/CT positivity, our results suggest that this modality may be considered even in the very low PSA BCR setting, especially when PSA doubling time is <12 months and/or the Gleason score is >7a. When such scanning is negative, the reason(s) could be the short-lived 68Ga radionuclide (half-life ~68 min) precluding late acquisition of interpretable images, coupled with the presence of lesions internalizing the PSMA-targeted tracer unusually slowly and/or with persistent residual physiological activity due to protracted clearance of the radiopharmaceutical . Preliminary data have suggested that imaging >=24 h post-injection with PET tracers labeled with longer-lived radionuclides, such as zirconium-89 (half-life ~3.3 days), may frequently detect lesions missed by PET/CT using radiotracers labeled with 68Ga or other short-lived radionuclides, such as 18F (half-life ~110 min) . The strengths and limitations of this analysis should be considered. The former includes a large study sample, dual-center participation, and long-term (~7 years) data from "real-world" practice, all contributing to the generalizability of our findings. Additionally, the statistically similar detection rates for the two centers suggest consistency in our results. Among the downsides of the analysis were a retrospective study design, limited data on PSA doubling time, and above all, a lack of histological, clinical, or imaging follow-up data regarding suspicious lesions. These limitations decrease certainty as to whether the detected lesions indeed corresponded to prostate cancer. Nonetheless, the lesions' locations, the considerable experience of the scan readers in acquiring and interpreting PET/CT images of men with prostate cancer, and the well-established sensitivity and specificity of 68Ga-PSMA-11 PET/CT to detect prostate malignancy all lend plausibility to the lesions indeed comprising such tumor. Notably, our study focused only on men who had undergone radical prostatectomy as primary treatment and on a single PSMA-targeted radiotracer, 68Ga-PSMA-11. It will be of interest to perform analogous analyses in men receiving radiation therapy as primary treatment and/or undergoing PET/CT with other such radiopharmaceuticals, e.g., 18F-PSMA-1007, 18F-DCFPyL, or 68Ga-PSMA-I&T. Especially the detection rate of local recurrence, which may be higher by using 18F-PSMA-1007 due to the hepatobiliary excretion mechanism with almost complete absence of urinary activity. 5. Conclusions This was a retrospective analysis of a ~7-year, dual-center, "real world" experience with 68Ga-PSMA-11 PET/CT in a large group (n = 115) of post-prostatectomy patients with BCR and increasing but very low PSA levels of <=0.2 ng/mL. Even in this setting, such imaging demonstrates a 25.2% (29/115) patient-level detection rate of lesions suspicious of prostate cancer. Given the increasingly clear patient outcome benefits of accurately localizing prostate cancer lesions at the earliest stage of recurrence, our observations suggest a potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology. Author Contributions Conceptualization, C.B., M.A.H., S.E. and F.R.; methodology, C.B., M.A.H., M.F. and F.R.; formal analysis, C.B., M.F, F.K., H.-G.B. and F.R.; investigation, C.B., M.F., M.A.H. and F.R.; data curation, M.F. and F.K.; writing--original draft preparation, C.B., R.J.M. and F.R.; writing--review and editing, all authors; visualization, M.F. and F.R.; supervision, M.S. and S.E. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of the Arztekammer des Saarlandes/Saarbrucken (approval number: 170/22, approval date: 13 September 2022) and the ethics committee of the Medical Association Rhineland-Palatinate (Laek Rlp) (approval number: 2018/13390, approval date: 29 October 2018). Informed Consent Statement Informed consent was obtained from all subjects involved in this study. Data Availability Statement The datasets used and analyzed during the present study are available from the corresponding author upon reasonable request. Conflicts of Interest The authors declare no conflict of interest. Abbreviations 18F Fluorine-18 68Ga Gallium-68 BCR Biochemical recurrence of prostate cancer BM Bone metastasis LR Local recurrence LN Lymph node metastasis MIP Maximum intensity projection NA Not available PET/CT Positron emission tomography/computed tomography p.i. Post-injection PSA Prostate-specific antigen PSMA Prostate-specific membrane antigen SD Standard deviation cancers-15-01376-t001_Table 1 Table 1 Patient characteristics of 115 men with BCR and very low PSA concentration. Characteristic Value Age, yr Median (minimum-maximum) 67.6 (48.4-85.7) Mean +- SD 66.9 +- 8.0 PSA, ng/mL Median (minimum-maximum) 0.13 (0.01-0.2) Mean +- SD 0.13 +- 0.06 Category, ng/mL, % (n) <=0.1 33.0% (38) >0.1-0.15 32.2% (37) >0.15-0.2 34.8% (40) PSA doubling time, months n = 83 Median (minimum-maximum) 4.9 (0.75-24) Category, % (n) <3 23% (19) 3-6 29% (24) >6-12 29% (24) >12 19% (16) Gleason score, % (n) unless otherwise noted n = 107 Minimum-maximum 6-10 6 8.4% (9) 7a 33.6% (36) 7b 24.3% (26) 8 15.0% (16) 9 15.9% (17) 10 2.8% (3) Additional treatment besides radical prostatectomy, % (n) Radiation therapy 8.7% (10) Androgen deprivation therapy 8.7% (10) Percentages represent proportions of the overall study sample or the subgroup with available data regarding a variable, as applicable. Due to rounding, not all percentages may add up to exactly 100%. Abbreviations: PSA, prostate-specific antigen, and SD, standard deviation. 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PMC10000221 | Due to the occurrence of plastic impaction in ruminants and its deleterious effects on health and production, it is necessary to determine the suitability of biodegradable polymers to replace polyethylene-based agricultural plastics, such as hay netting. The objectives of this study were to evaluate the clearance of a polyhydroxyalkanoate (PHA) and poly(butylene succinate-co-adipate) (PBSA) melt-blend polymer from the rumen when fed to cattle and subsequent animal health. Twelve Holstein bull calves were dosed with an encapsulated 13.6 g of PBSA:PHA (Blend), 13.6 g of low-density polyethylene (LDPE), or four empty gelatin capsules (Control) for 30 d. The feed intake, body weight, and body temperature were evaluated, and hemograms were run on d 0 and d 30. On d 31, calves were euthanized to evaluate gross rumen measurements and pathology, papillae length, and polymer residues in rumen contents. No calves presented any signs related to plastic impaction. The feed intake; body weight; rectal temperature; hematological parameters; gross rumen measurements and pathology; and rumen pH and temperature were not affected by treatments. Calves dosed with LDPE had 27 g of undegraded polymer retained in the rumen while Blend calves had only 2 g of fragmented polymers that were 10% of their original size. Agricultural plastics developed from PBSA:PHA may be a suitable alternative to LDPE-based products in the case of animal ingestion and may reduce the incidence of plastic impaction. biodegradable polyhydroxyalkanoate poly(butylene succinate-co-adipate) rumen plastic impaction Virginia Agricultural Council781 This research was funded by the Virginia Agricultural Council, project number 781. pmc1. Introduction Plastic impaction is detrimental to ruminant health and should be a concern for the dairy industry as it unfavorably impacts the rumen environment and animal productivity. Though no surveys have yet evaluated occurrences in the United States, it is estimated that 20% of cattle are affected by plastic impaction, according to abattoir studies in the East . Plastic impaction occurs when large amounts of indigestible plastic materials are indiscriminately ingested by ruminants in either a single meal or over the lifetime of the animal. These materials may be introduced into cattle rations by chopping forages with intact netting. In this condition, it is estimated that 0.07% of the diet contains polyethylene-based plastics . When these materials enter the reticulorumen, they aggregate together to form large ball-like masses that press against rumen epithelium during rumination . With a long-term presence, plastics reduce rumen functionality and may impact feed efficiency. This is through decreasing ruminal movement and the methylene blue reduction time of rumen fluid, an indirect measure of microbial fermentation , and inducing pathological alterations to the rumen epithelium . To reduce the incidence of plastic impaction, it is crucial to identify biodegradable alternatives to polyethylene that will safely degrade within the rumen environment with no harmful effects on animal health. Potential alternative plastic materials include polyhydroxyalkanoates (PHAs) and other biodegradable polymers such as poly(butylene succinate-co-adipate) (PBSA). We previously evaluated the in vitro ruminal degradation of PHA, PBSA, PBSA:PHA melt-blend, and low-density polyethylene (LDPE) polymers in rumen fluid for 10 days. This study demonstrated the potential for biodegradable polymers to begin the degradation process within 24 h in rumen fluid . We further evaluated the in situ ruminal degradation of PHA, PBSA, PBSA:PHA, and LDPE films in dairy cattle for 150 d . The results of this experiment confirmed that polyethylene materials do not degrade within the rumen and that a PBSA:PHA blend may be the best material to replace LDPE for net wrap applications. Although mass loss did not occur until 120 d, the PBSA:PHA blend began to fragment to 29% of its original size by just 24 h of inclusion in the rumen . Thus, this polymer blend may fragment enough to pass through the reticulo-omasal orifice and through the rest of the digestive tract, decreasing the incidence of plastic accumulation within the rumen compared to polyethylene-based products. Before the development of plastic net wraps from a PBSA:PHA material can be considered, in vivo studies that evaluate the clearance of PBSA:PHA from the reticulorumen after feeding and subsequent influences on animal health are necessary. The objectives of this study were to (1) evaluate the clearance of a PBSA:PHA melt-blend polymer from the rumen compared to LDPE and (2) evaluate animal health when these materials are fed to cattle. We hypothesized that, unlike LDPE-fed cattle, PBSA:PHA would fragment in the rumen and pass through the reticulorumen and that health parameters would not differ from healthy control cattle. 2. Materials and Methods 2.1. Treatment Preparation A 10% PHA and 90% PBSA polymer blend (w/w) was developed by melt-blending and extruding a proprietary PHA-based polymer (Mirel P1004, Metabolix, Inc., Woburn, MA, USA) and PBSA (Bionolle 3001MD, Showa Denko America, Inc., New York, NY, USA) into a nurdle formation using a pilot-scale extruder at Alterra Plastics (Clifton, NJ, USA). Low-density polyethylene nurdles were purchased from Sigma-Aldrich, Inc. (St. Louis, MO, USA). Films were produced from polymer nurdles using a melt press (#SP210C-X351220, PHI Hydraulics, Inc., City of Industry, CA, USA). Nurdles were placed between two non-stick Kapton sheets on platens set to 174 degC and incremental pressure to 340 kg. The bottom platen was raised near the top platen, and the polymer nurdles were given roughly 30 s to soften before the bottom platen was raised entirely. The polymer nurdles were melted for approximately 30 s to form circular films 0.1 mm thick. Circular films were then run through a cross-cutting paper shredder (#ITSH-555, Innovative Technology Americas, Inc., Pewaukee, WI, USA) with 4 mm blades to produce PBSA:PHA and LDPE film strips that were 50.4 +- 19.1 mm long. To prepare daily boluses for treatments, 3.4 g of PBSA:PHA or LDPE films was packed in 7.5 mL Torpac gelatin capsules (Fairfield, NJ, USA). Three daily treatments were utilized in this study: 4 empty gelatin capsules (Control), 13.6 g of PBSA:PHA in 4 gelatin capsules (Blend), or 13.6 g of LDPE in 4 gelatin capsules (LDPE). 2.2. Calf Health and Management The Virginia Polytechnic Institute and State University Animal Care and Use Committee approved all animal procedures (IACUC #19-265). Calves were chosen as the subject for this study due to their heightened sensitivity to toxicities compared to fully mature cows. In this 6-week study, 12 weaned Holstein bull calves were purchased from a single farm (Floyd, VA, USA) and transported to Virginia Tech (Blacksburg, VA, USA). Upon arrival, calves were evenly grouped into 4 blocks by age (62 +- 9 d) and initial body weight (74.9 +- 8.0 kg). Calves were individually housed in tie-stall pens (122 cm x 183 cm) in temperature- (20 degC) and light-controlled rooms (12 h of light) for the duration of the study. Pens were placed on top of rubber mats (122 cm x 183 cm) and pine shavings were provided for bedding. Calves had visual and auditory contact with each other, as well as nose-to-nose contact between adjacent stalls. Calves were acclimated for 14 to 15 d before the start of the treatment period depending on the start of treatment administration as described below. Upon arrival, calves were offered 2.3 kg of calf starter (Producer's Pride, Brentwood, TN, USA), ad libitum mixed-grass hay, and ad libitum water. According to the manufacturer's specifications, the calf starter contained 16.2% crude protein, 1.6% crude fat, 13.0% crude fiber, and 17.0% acid detergent fiber. On a dry matter basis, the mixed-grass hay contained 12.7% crude protein, 61.6% neutral detergent fiber, 36.3% acid detergent fiber, and 3.8% lignin. Calves were acclimated to 2.7 kg of starter by d 0 and continued to receive ad libitum mixed-grass hay and water. Feeding occurred once daily at 07:00 and refusals for starter and hay were weighed separately the next morning before feeding. Calves were randomly assigned to treatments as a randomized complete block design such that within each of the four blocks one calf each was assigned to Control, Blend, or LDPE treatment. Treatment administration occurred directly after feeding via a plastic bolus gun from d 0 to d 30. Two blocks were randomly selected to start one day, and the remaining two blocks started the next to ensure treatments were administrated for 30 d before tissue collection on two consecutive dates. The treatment period of 30 d was chosen such that, if polymer did not escape the rumen, 408 g (approximately 0.5% of the calf body weight) would be retained in the rumen. It was hypothesized that this level of accumulation would cause histopathological damage as seen by Otsyina and colleagues . Calf health was assessed twice daily, at 07:00 with feeding and again at 15:00. Rectal temperature, fecal score, obvious treatment presence in fecal matter, bloat occurrence, eye score, nasal score, and activity were evaluated. According to the University of Wisconsin Madison School of Veterinary Medicine's Calf Health Scoring Chart, fecal score was evaluated with a 5-point scale: 1 = watery, 2 = loose, 3 = semi-formed and pasty, 4 = hard pellets, and 5 = normal. Eye score was evaluated with a 4-point scale: 1 = heavy ocular discharge, 2 = moderate bilateral discharge, 3 = limited discharge, and 4 = no discharge. Nasal score was evaluated with a 4-point scale: 1 = copious amounts of mucus discharge, 2 = bilateral cloudy mucus discharge, 3 = small amount of unilateral discharge, and 4 = no discharge. It was noted if a calf exhibited a fecal, nasal, or eye score equal to or below 2, lethargy with depressed ears, a cough or elevated respiration rate, a rectal temp above 40.0 degC, or a reduced feed or water intake. A veterinarian was sought if any of these signs presented for more than a day or if two or more of these symptoms occurred simultaneously. Every week, calves were weighed by walking onto scales, and average rectal temperature, daily grain intake, and daily hay intake were determined. 2.3. Hematological Evaluation Whole blood samples were collected from animals via the venipuncture of the jugular vein into 7 mL vacutainers containing potassium ethylenediaminetetraacetic acid (3EDTA) on d 0 and d 30 of bolus administration. Within an hour of collection, approximately 1 mL of blood mixed with EDTA was taken up by a syringe for determination of erythrocyte sedimentation rate (ESR) using the Wintrobe tube method to determine potential inflammatory activity. The blood was deposited into perpendicular Wintrobe tubes to the zero mark. After 24 h, the fall of red-packed cells was measured in millimeters. The remaining blood samples were delivered to the Virginia Tech Animal Laboratory Services (VITALS) within 2 h of collection for the determination of red blood cells (RBCs), hemoglobin (HB), hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), reticulocytes, white blood cells (WBC), neutrophils, monocytes, eosinophils, basophils, platelets, and mean platelet volume (MPV) via a Sysmex XN-1000 (Sysmex America, Inc., Lincolnshire, IL, USA). 2.4. Tissue Collection and Gross Rumen Measurements Calves were slaughtered via captive-bolt stunning followed by exsanguination on d 31 between 08:00 and 11:00, at least 2 h after feed was removed. The entire gastrointestinal tract was ligated and removed from the carcass. The full forestomach was removed, weighed in full, and then segmented at the reticulo-omasal orifice. The reticulorumen was then weighed in full before being opened to measure the pH and temperature of the rumen contents immediately. A small sample of total contents was strained with cheesecloth by hand to retrieve approximately 10 mL of rumen fluid to determine its methylene blue reduction time (MBRT). The MBRT was determined as the time for the blue coloration to disappear from the rumen fluid after 0.5 mL of 0.04% methylene blue solution was added . The total rumen contents were then thoroughly mixed by hand and a small sample was collected, approximately 200 g. The total weight of the sample was determined, and then the rumen solids were strained through two layers of cheesecloth and reweighed. Solids were flash-frozen until further analysis to determine the amount and size of polymer residues present. All solids were evacuated from the reticulorumen and then subjectively scored using a 5-point scale: 0 = no polymer present, 1 = small amount of degraded polymer present, 2 = degraded polymer present throughout contents, 3 = small amount of intact polymer present, and 4 = intact polymer present throughout contents. The empty reticulorumen was weighed to determine the total rumen contents and then rinsed to remove any remaining particles loosely attached. The reticulorumen was "butterfly-cut" for a full visual of the epithelium. The epithelium was grossly evaluated in the cranial dorsal, caudal dorsal, cranial ventral, and caudal dorsal regions using a 6-point scoring system following Jonsson et al. : 0 = no evidence of any damage, 1 = palm-size or smaller areas bare of papillae, 2 = large areas bare of papillae, 3 = areas of scarring, 4 = red/bloody areas, and 5 = areas of parakeratosis. Rumen epithelium samples for papillae measurements were obtained from the cranial dorsal and caudal ventral regions using a scalpel and a 3 cm x 10 cm stencil. Epithelium samples were stapled to wooden tongue depressors and immediately placed in 10% formalin to fix for 48 h. 2.5. Rumen Histological Measurement Epithelium sections of 0.5 cm were cut from fixed tissue samples, placed in cassettes in 10% formalin, and sent to VITALS for routine processing. This included embedding in paraffin, sectioning 5 mm thick sections and mounting them onto three positively charged microscope slides, and hematoxylin and eosin staining following standard procedure. Digital images of slides were taken at 4x using an Olympus BX43 microscope (Olympus Corporation of the Americas, Center Valley, PA, USA) fitted with a Retiga R6 camera (QImaging Corporation, Surrey, BC, Canada). Images were viewed in ImageJ (U.S. National Institutes of Health, Bethesda, MD, USA) for measurement of papillae length using the line tool. Three random papillae from each slide were selected and measured. 2.6. Polymer Residues Frozen rumen solids samples were thawed to room temperature and then dried in a forced-air oven at 55 degC for 48 h. The total dried sample weight was determined and polymer particles were manually removed with forceps. Residual polymers were weighed in total and then three random particles were selected, and their length was measured with digital calipers. The total residual polymer present within the rumen was estimated using the following:(1) Accumulation g=contents gxsolids %xDM %xpolymer % where contents indicates the total weight of all rumen contents, solids indicates the ratio of solids to total weight of rumen contents, DM indicates the dry matter content of solids, and polymer indicates the ratio of polymer to dry solids weight. 2.7. Statistical Analysis Unless otherwise mentioned, all data were analyzed using the MIXED procedure and least-squared differences were adjusted by Tukey's method in SAS 9.4 (SAS Institute, Cary, NC, USA). Following a Box-Cox transformation, the average daily grain intake was transformed by the power of 5, and the average daily hay intake was transformed by taking the square root to improve the normality of the data for statistical analysis. Grain intake, hay intake, body weight, and rectal temperature were analyzed with the fixed effects of treatment, week, the interaction, and the random effect of block. Weekly observations were the repeated measures and animals were the subjects. The autoregressive covariance structure was used according to the AIC criterion. Hematological parameters were analyzed with the fixed effects of treatment, sampling day, the interaction, and the random effect of block. The sampling day was the repeated measure and animals were the subjects. The autoregressive covariance structure was used according to the AIC criterion. Subjective scoring parameters of rumen contents and gross pathology of epithelium regions were analyzed using PROC FREQ and the fixed effect of treatment. Papillae length was analyzed with the fixed effects of treatment, region, the interaction, and the random effects of block and slaughter date. Forestomach weights, MBRT, rumen pH and temperature, estimated polymer accumulation, and polymer length were analyzed with the fixed effect of treatment and the random effects of block and slaughter date. Statistical significance was determined at p < 0.05 and statistical tendency was determined at p < 0.10. 3. Results 3.1. Animal Growth and Health Neither average daily grain nor hay intake were affected by the interaction of treatment and sampling day, nor treatment by itself . However, both daily feed intakes increased with time. On an as-fed basis, calves ate 1.77 kg of grain on average during the second acclimation week. Average daily grain intake increased by 16% by d 0 (p < 0.01) and this percent increase was maintained to d 7 (p < 0.01). The increase in grain intake slowed to an 11% increase from d 7 to d 14 at 2.66 kg (p < 0.01), after which the average daily grain intake was maintained through d 28. Meanwhile, the average daily hay intake increased throughout the study at a slower rate. Calves ate very little hay during the second acclimation week at only 0.05 kg. This increased threefold by d 0 (p < 0.01) and then nearly twofold by d 21 (p < 0.01). By d 28, the average daily hay intake reached 0.50 kg. The increased feed intake over time was accompanied by increased body weight. The body weight of bull calves was also not affected by the interaction or treatment by itself. The body weight increased linearly from week to week by approximately 5% . At d 7, calves were 79.01 kg, and by d 28, they increased to 104.55 kg with an average daily gain of 0.73 kg/d. Regarding calf health, rectal temperature was not affected by any of the fixed effects and averaged 38.1 degC. Calves did not demonstrate bloat, scours, absence of fecal matter, reduced feed intake, reduced body weight gain, or abnormal behaviors such as kicking at the stomach and stomping that would have indicated any gastrointestinal blockage due to polymer build-up in the tract. However, calves did develop signs of bovine respiratory disease shortly after arriving at Virginia Tech. All calves were blanket-treated with tulathromycin (IncrexxaTM, Elanco, Greenfield, IN, USA) and an intranasal bovine rhinotracheitis-parainfluenza 3-respiratory syncytial virus vaccine (Inforce 3(r), Zoetis, Parsippany, NJ, USA) by the attending veterinarian. By d 0, signs of illness subsided and calves were deemed healthy to begin the study. 3.2. Hematological Parameters Hematological parameters were unaltered by the administration of polymer treatments (Table 1). When comparing blood parameters from d 0 to d 30 within treatment groups, only WBC, neutrophil count, and platelet count seemed to be affected. The white blood cell count tended to decrease by 35% in LDPE calves (p = 0.08) but did not change for the other two groups. Neutrophil counts tended to decrease by 76% in Control calves (p = 0.07) and nearly halved in LDPE calves (p = 0.03) but did not change for Blend calves. The platelet count decreased by 30% for Control calves (p = 0.01) and decreased by 40% for LDPE calves (p < 0.01) but did not change for Blend calves. 3.3. Rumen Measurements Rumen measurements are displayed in Table 2. Gross rumen measurements of total forestomach weight, reticulorumen weight, empty reticulorumen weight, and total rumen contents did not differ among the treatment groups. Rumen temperature and pH also did not differ among treatments. However, there was a tendency for MBRT to be affected by treatment. Blend calves tended to have reduced MBRT compared to LDPE calves by 46 s (p = 0.06). Gross evaluation of epithelium in the cranial dorsal, caudal dorsal, cranial ventral, and caudal ventral regions of the reticulorumen epithelium did not reveal any significant differences between treatment groups (p = 0.34). In Control and LDPE calves, no region had evidence of any damage as indicated by a score of 0. One calf in the Blend group demonstrated a very small patch of bare papillae in both dorsal regions of the epithelium. However, these areas were not paired with any scarring, ulcerations, inflammation, or any other indicators of severe damage. 3.4. Papillae Measurements A treatment and epithelium region interaction existed for the lengths of papillae . Within samples taken from the caudal ventral region of the reticulorumen, papillae of Blend calves were 4.24 mm and 50% longer than those of Control calves (p = 0.04) but did not differ from those of LDPE calves at 3.56 mm. Papillae from LDPE calves also did not differ from those of Control calves, which were just 2.84 mm long. The papillae length of the cranial dorsal region was not affected by treatment and averaged 4.33 mm. However, papillae from the cranial dorsal region were significantly longer by 61% than those from the caudal ventral region in Control calves (p < 0.01). In gross evaluation of reticulorumen integrity, no apparent disruption of the epithelium was appreciated for any treatment or region. Neither atrophy, an obvious stunting of papillae, necrosis, the shredding of stratified epithelium, nor hyperplasia were detected. 3.5. Polymer Residues In subjective scoring of rumen contents for polymer residues, treatment had a significant influence (p < 0.01). All Control calves received a score of 0, indicating no polymer presence. Blend calves all received a score of 1 indicating a small amount of degraded polymer present. Half of the LDPE calves demonstrated a score of 3 and the other half demonstrated a score of 4, indicating small and large amounts of intact polymer present within rumen contents, respectively. Polymer residues within rumen contents presented as individual film strips or shards. No apparent aggregation of polymer residues was evident with any treatment group. This trend was reflected in the estimated polymer accumulation in the rumen and the length of residual polymers. Calves that received LDPE had significantly more polymer residues entrapped in the rumen compared to Blend calves . Calves that received LDPE polymers retained approximately two days' worth of polymer (7% of the total 408 g of polymer dosed), while Blend calves retained only 13% of a single day's dosage (0.4% of the total 408 g dosed). Lengths of polymer residues were also different between treatment groups . Polymers retained in the rumens of LDPE calves were 49.51 mm long, which was 10 times the length of Blend residues at just 4.81 mm long (p < 0.01). 4. Discussion To our knowledge, this is the first study to specifically evaluate if a PBSA and PHA biodegradable polymer blend would degrade and pass from the reticulorumen of dairy cattle if ingested compared to a polyethylene control. We hypothesized that LDPE, given its indigestible nature, would accumulate in the rumen and unfavorably impact animal health, while PBSA:PHA would fragment and not impact calf health. However, our findings demonstrated that neither a PBSA:PHA polymer melt-blend nor traditional LDPE influenced the health or growth of Holstein bull calves at approximately 0.5% inclusion of the diet, as fed, for 30 d. Due to increased rumen filling by the accumulation of plastics and other indigestible foreign materials in the rumen and subsequent activation of stretch receptors in rumen epithelium, satiety centers in the hypothalamus are stimulated and create a sense of fullness by the animal . A decreased feed intake would thereby reduce available energy for the animal and weight gain would theoretically decrease. Though limited studies evaluate plastic impaction in cattle in controlled environments, studies that evaluated animals diagnosed with plastic impaction at abattoirs demonstrated these characteristics. Animals with plastic foreign bodies within the rumen consumed less food and were subsequently 13% lighter than healthy animals . Animals similarly demonstrated poor body condition scores highly correlated to increased amounts of plastic materials trapped in the rumen . However, these studies were more observatory and evaluated animals after accumulation occurred over a productive lifetime. The depth at which plastic accumulation influences these parameters and a threshold value before the feed intake and body weight decrease in cattle cannot be estimated at this time. The calves utilized in this study were only 2 months old and presumably not exposed to plastic materials before this study. Only 27.42 g and 1.72 g of LDPE and PBSA:PHA were estimated to be maintained in the rumen after 30 d of daily ingestion. This is equivalent to 0.3% and 0.02% of total rumen contents. Likely, polymer accumulation in this study was not enough to stimulate rumen filling and satiety to reduce the feed intake and, subsequently, reduce growth. Previous observational and controlled studies of plastic impaction in ruminants demonstrated alterations in hematological parameters compared to healthy animals. Observational studies found that the WBCs , RBCs, and Hb were reduced in animals with plastic impaction while the MCV and MCHC were elevated . A controlled study in which sheep were implanted with plastic via rumenotomy for 42 d found, at just 129 g of plastic, or 0.5% body weight, sheep had reduced WBCs, RBCs, and HB and increased MCV. The MCHC was not elevated until 258 g of plastic implantation, and platelet counts were increased in animals implanted with 387 g . Our study found the WBC to change in LDPE calves with a 35% reduction rather than an increase as previously seen. All our calves exhibited signs of bovine respiratory disease during the acclimation period. Though calves were treated and deemed healthy to begin the experiment by d 0, The WBC count could have still been elevated from the disease. Initial WBC counts for LDPE calves were the greatest of the three treatments and slightly elevated compared to a reference value of 8 wk old calves . However, values still fell into the accepted range of 2.71 to 17.76 x 103 cells/uL as provided by VITALS. It is likely that the WBC count reduction after 30 d was due to recovery from the disease rather than LDPE administration as the Control and Blend groups also had slight reductions despite not being significant. Neutrophil counts also decreased for Control and LDPE calves after 30 d. However, neutrophil counts remained within the normal range of 0.7 to 6.9 x 103 cells/uL as given by VITALS. Again, the trend of decreasing over time is likely explained by the recovery of animals from bovine respiratory disease during the acclimation period rather than a treatment effect. This is especially so as Control animals displayed this trend. Platelet counts similarly decreased after 30 d for Control and LDPE calves. Platelets play a key role in the inflammatory response and counts increase during times of inflammation throughout the body . Bovine respiratory disease is highly associated with the inflammation of the respiratory tract. Elevated levels of platelets in this study may be due to this inflammatory response. Platelet counts returned to normal values after 30 d, indicating the recovery of the animals and a lack of rumenitis due to polymer presence. The absence of a true treatment effect, namely LDPE, on changing histological parameters can be explained by the small accumulation of polymer within the rumen contents and the short duration of the study. The gross rumen development was not affected by treatment; the total forestomach weight, total reticulorumen weight, and empty reticulorumen weight were not different among treatments. The influence of plastic impaction on rumen growth has not yet been evaluated in any ruminant species. As previously described, most studies evaluating plastic impaction are post-impaction observations of mature animals when rumen growth and development have ceased. Because polymer accumulation was slight in this study and only for 30 d, it is unknown if polymer presence would influence rumen development in growing animals. Severe plastic impaction in young animals may lead to a reduced feed intake and therefore decreased available nutrients to support the growth of the gastrointestinal tract. However, it is doubtful that a severe accumulation of plastics would occur in young animals in standard production conditions in the United States. Total mixed rations contain approximately 0.07% chopped net wrap on an as-fed basis when hay bales are ground with intact netting . Thus, accumulation may be slow enough that rumen development would be complete before a significant influence by LDPE-based materials. No studies to date have specifically evaluated this and further studies are needed to specifically evaluate the effect of plastic impaction on rumen growth in developing animals under normal feeding conditions. Similarly, internal rumen parameters did not differ among treatments. Previous observational studies indicate that animals with plastic foreign body impaction typically have an increased MBRT and rumen pH compared to healthy animals . The methylene blue reduction time is an important parameter to evaluate as it is indicative of the fermentation redox potential and activity of microbes in rumen fluid. Healthy animals typically have an MBRT of 180 s or less, while animals with plastic impaction may have fourfold increases depending on the level of accumulation . This increase in the MBRT is due to the decreased activity of microbes, likely due to the reduced rumen motility and reduced feed intake of animals with severe plastic impaction . The average MBRTs of Control, Blend, and LDPE calves were all under 180 s, and thus it can be concluded that microbial fermentation was not particularly diminished. A potential explanation for the reduced MBRT in Blend calves compared to LDPE calves could be degradation products released from the PBSA:PHA melt-blend, more specifically the PHA component. Although we have yet to evaluate specific degradation products released by this polymer in rumen fluid, butyrate concentrations within rumen fluid may increase due to the release of 3-hydroxybutyrate from PHA biodegradation . Depending on the extent of butyrate released into the rumen pool, total volatile fatty acid concentrations may increase and reduce the rumen redox potential . More negative rumen redox potential is highly associated with improved microbial fermentation activity . It may be through this mechanism that the MBRT is reduced in animals dosed with the PBSA:PHA melt-blend. However, if volatile fatty acid concentrations were increased in Blend animals, they were not sufficient enough to decrease pH as previously seen in feeding studies of poly(3-hydroxybutyrate) to aquatic species such as the European sea bass . Further studies with more animals fed a PBSA:PHA melt-blend should evaluate its biodegradation products, its influence on the microbial ecology, and the redox potential of the rumen to sufficiently determine the long-term influences of this polymer on ruminal fermentation. In gross evaluation of the epithelium, observational studies consistently found that animals with plastic foreign bodies present with rumenitis, hemorrhaging, erosion and sloughing of rumen mucosa, lesions, regions bare of papillae, and bent and stunted papillae . These observations were explained by the aggregation of plastic materials forming ball-like masses, which press against the rumen epithelium during rumination. These observations were not evident in the present study with either Blend or LDPE treatments in any of the four regions of the reticulorumen. Polymer residues in this study did not aggregate together to form masses of material and polymers seemed to be equally distributed among the rumen contents. The lack of aggregation of the limited polymer residues likely explains the absence of pathological damage to the rumen epithelium and mucosa. To fully appreciate if a PBSA:PHA blend polymer would induce pathological damages to the rumen compared to a LDPE polymer control, feeding studies of a longer duration with netting prototypes developed from these materials need to be conducted. Though gross pathological changes were not observed, papillae length was influenced by polymer introduction to the rumens of Holstein bull calves. A previous study measured the lengths of papillae from the dorsal rumens of goats and ewes that presented plastic foreign bodies. Compared to healthy animals, papillae from affected animals were 60% shorter . Additionally, papillae length was negatively correlated to the amount of foreign material present within the rumen. In the present study, papillae length within the cranial dorsal region of calves did not differ among those that received either a biodegradable polymer or LDPE compared to animals that did not receive any polymer. The drastic difference in accumulation between the previous study and this one likely explains this. Though the duration of accumulation in the referenced study is unknown, plastic accumulation was on average 2.75 kg . This is 100 times more than what accumulated in our study over 30 d. Interestingly, in the caudal ventral region, Blend calves' papillae were 50% longer than Control calves. It is possible that the degradation of the PHA component of the PBSA:PHA melt-blend introduces exogenous butyrate into the rumen. Butyrate is a vital modulator in the functional development of the rumen epithelium and is involved in cellular proliferation pathways . As such, butyrate potentially released from this polymer may have stimulated epithelium development and increased papillae lengths. However, Blend calves' papillae length in the caudal ventral region were not different from the papillae of LDPE calves. Repeated studies with more animals for a longer duration to accrue more polymer residues are necessary to further discern this relationship. Despite the apparent health of animals in the face of LDPE administration for 30 d, the characterization of residual polymers in rumen contents indicates PBSA:PHA may be a better material than LDPE for single-use agricultural plastics in the case of ingestion. Animals dosed with 13.6 g of LDPE daily had 16 times more polymer residues entrapped in the rumen than those dosed with 13.6 g of PBSA:PHA daily. This indicates that accumulation occurs at a much faster rate for LDPE than PBSA:PHA material. However, the accumulation of LDPE in the rumen was lower than expected. A study in which a total mixed ration containing 0.07% chopped plastic net wrap was fed to cattle for 7 months found that 47.2% of net wrap remains in the reticulorumen in ball-like masses . Our study found that only 6.7% of administered LDPE was retained. Given that this polymer is indigestible, as seen in our previous in situ results , polymers could have escaped the rumen and been excreted or regurgitated during rumination. The net wrap feeding study also found that plastic particles that were retained in the rumen were more than 70 mm long in mature cattle whereas the polymers utilized in this study were only 50 mm long. It is possible that some polymers were shorter than the average and escaped through the reticulo-omasal orifice. The lack of aggregation of polymer materials in the rumen also left polymers freely distributed among rumen contents. This could have increased the likelihood of ruminal escape. The absence of aggregation of the PBSA:PHA polymer may better be explained by the breakdown of the material as indicated by reduced fragment size. This reduced residual polymer size likely allowed PBSA:PHA to better escape the ruminal environment and thus decrease accumulation within the rumen. It is important to note that this study utilized young Holstein calves, and characteristics of polymer degradation may not entirely reflect degradation in a mature cow. The ruminal microbiome is moldable within the first few months with the rumen being newly inoculated. It takes approximately 90 d for the rumen microbiome to be established and to stabilize . As the ruminant matures, the microbiome continues to be inoculated with bacteria from the animal's environment, thus providing more opportunities for polymer-degrading bacteria to be hosted. The degradation of PHA and PBSA may be improved in older animals due to increased microbial concentrations and the greater likelihood of PBSA-degrading bacteria being present. Therefore, the passage of PBSA:PHA materials through the rumen may be improved in older animals that may consume these products. 5. Conclusions Based on these preliminary findings, we suggest that feeding LDPE or PBSA:PHA polymer films at 13.6 g/d to Holstein bull calves for 30 d does not negatively impact animal health or development. Due to the undegradable nature of LDPE in the rumen, LDPE accumulated more than PBSA:PHA. Biodegradable PBSA:PHA degraded to smaller fragments that more readily escaped the reticulorumen. Based on these results, we hypothesize that PBSA:PHA may be a suitable material to replace polyethylene in the development of net wraps in the case of animal ingestion due to its reduced aggregation within the rumen. Future studies with greater animal numbers should evaluate the long-term inclusion of net wrap materials developed from PBSA:PHA in total mixed rations. Histological parameters; rumen development, pathology, and morphology; volatile fatty acid concentrations; polymer degradation products and their transference throughout the body; rumen fluid redox potential; the distribution of a net wrap throughout the entire gastrointestinal tract; and the net wrap passage rate should all specifically be determined. Acknowledgments We thank Kayla Alward, John McGehee, Mingsi Liao, and other students for assistance in animal care and management. We also thank Jordan Wicks, Alyshia Talmage, and Con-Ning Yen for assistance in harvesting. Many thanks to Randy Chambers of William & Mary College (Williamsburg, VA, USA) for their assistance in the conceptualization of this work. The authors acknowledge that the data contained within this article was previously published in a MSc thesis, "Ruminal Degradation of Polyhydroxyalkanoate and Poly(butylene succinate-co-adipate" . Author Contributions Conceptualization, H.G., G.F., A.W., K.H., J.M. and R.C.; Methodology, H.G.; Validation, H.G.; Formal analysis, H.G.; Investigation, H.G.; resources, S.V., J.D., K.H. and J.M.; Data curation, H.G.; Writing--original draft preparation, H.G.; Writing--review and editing, H.G., J.D., G.F. and R.C.; Visualization, H.G.; Supervision, J.D., G.F., A.W., K.H., J.M. and R.C.; Project administration, H.G. and S.V.; Funding acquisition, G.F., A.W. and R.C. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The animal study protocol was approved by the Animal Care and Use Committee of Virginia Tech (protocol 19-265; approved 24 February 2020). Informed Consent Statement Not applicable. Data Availability Statement There are no publicly available data due to commercial restrictions of the products. Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Figure 1 Average daily feed intake determined on a weekly basis, as fed, of Holstein bull calves given either empty gelatin capsules (Control), 13.6 g of a poly(butylene succinate-co-adipate) and polyhydroxyalkanoate melt-blend (Blend), or 13.6 g of low-density polyethylene (LDPE) for 30 d, separated by average daily grain intake (A) and average daily hay intake (B). For grain intake, Treatment: p = 0.35; Day: p < 0.01; Treatment x Day: p = 0.61. For hay intake, Treatment: p = 0.84; Day: p < 0.01; Treatment x Day: p = 0.58. Data are shown as least-squared means of treatments within time (LSM +- SEM). Figure 2 Weekly body weights of Holstein bull calves given Control, Blend, or LDPE treatments for 30 d. Treatment: p = 0.70. Day: p < 0.01. Treatment x Day: p = 0.15. Data are shown as least-squared means of treatments within time (LSM +- SEM). Figure 3 Papillae length in the caudal ventral (CaV) and cranial dorsal (CrD) regions of the reticulorumens of Holstein bull calves after 30 d of Control, Blend, or LDPE treatment administration. Treatment: p = 0.19. Region: p < 0.01. Treatment x Region: p < 0.01. a,b Different letters indicate differences between treatments within epithelium region. * Indicates a significant difference between regions within treatments. Data are shown as least-squared means of treatments within region (LSM +- SEM). Figure 4 Characterization of polymer residues within rumen contents of Holstein bull calves given either Blend or LDPE treatment for 30 d, separated by (A) estimated total polymer accumulation and (B) average polymer length. For both parameters, treatment: p < 0.01. a,b Different letters indicate differences between treatments. Data are shown as least-squared means of treatments (LSM +- SEM). animals-13-00928-t001_Table 1 Table 1 Hematological parameters of Holstein bull calves at 0 d (Initial) and 30 d (Final) of administration of either 4 empty gelatin capsules (Control), 13.6 g of a poly(butylene succinate-co-adipate) and polyhydroxyalkanoate melt-blend in 4 gelatin capsules (Blend), or 13.6 g of low-density polyethylene in 4 gelatin capsules (LDPE). Parameter Control Blend LDPE SEM p < Initial Final Initial Final Initial Final 1 Trt 2 Ti Trt x Ti Red blood cell, cells/uL 10.63 10.33 11.57 11.24 10.54 10.71 0.50 0.25 0.66 0.80 Hemoglobin, g/dL 10.68 10.80 11.30 11.35 10.95 11.50 0.48 0.54 0.46 0.79 Hematocrit, % 36.03 35.80 38.03 37.23 36.65 38.18 1.48 0.47 0.89 0.72 Mean corpuscular volume, fL 33.88 34.78 32.90 33.10 34.83 35.65 0.68 0.02 0.06 0.62 Mean corpuscular hemoglobin concentration, g/dL 29.60 30.18 29.70 30.50 29.85 30.13 0.36 0.83 0.06 0.74 Red cell distribution width, % 27.63 26.18 27.95 27.75 26.88 26.33 1.16 0.72 0.03 0.26 Reticulocyte, cells/uL 0.85 1.75 1.15 1.98 1.80 1.63 0.58 0.81 0.16 0.40 White blood cell, cells/uL 9.67 8.13 9.19 8.43 10.17 7.55 x 0.96 1.00 0.01 0.35 Neutrophil, cells/uL 4.48 2.55 x 4.48 3.00 4.50 2.23 a 0.70 0.82 <0.01 0.68 Lymphocyte, cells/uL 3.73 4.05 3.53 3.90 3.95 4.03 0.39 0.83 0.17 0.77 Monocyte, cells/uL 1.30 1.40 1.03 1.40 1.53 1.18 0.17 0.59 0.72 0.06 Eosinophil, cells/uL 0.00 0.03 0.05 0.03 0.08 0.00 0.03 0.69 0.23 0.15 Basophil, cells/uL 0.10 0.15 0.10 0.13 0.13 0.10 0.02 0.74 0.29 0.16 Platelets, cells/uL 684.75 526.00 a 703.50 643.50 681.75 486.50 a 33.56 0.10 <0.01 0.08 Mean platelet volume, fL 7.03 7.15 7.30 7.38 7.18 7.05 0.22 0.42 0.81 0.57 Erythrocyte sedimentation rate, mm/24 h 4.52 4.34 4.98 4.08 4.11 4.11 0.49 0.50 0.35 0.59 1 Treatment effect; 2 sampling time effect; a indicates a significant difference from the initial value within treatment, p < 0.05; x indicates a tendency to differ between time points within treatment, p < 0.10; data shown are the least-squared means. animals-13-00928-t002_Table 2 Table 2 Rumen parameters of Holstein bull calves after 30 d of administration of either Control, Blend, or LDPE treatment. Parameter Control Blend LDPE SEM p < Forestomach, kg 16.04 14.57 16.19 1.29 0.24 Reticulorumen, kg 12.44 11.58 13.02 1.20 0.25 Empty reticulorumen, kg 2.11 2.08 2.20 0.18 0.63 Rumen contents, kg 10.33 9.50 10.82 1.09 0.35 Methylene blue reduction time, s 143 xy 108 y 154 x 17 0.06 Rumen pH 6.8 6.8 6.9 0.1 0.61 Rumen temperature, degC 37.8 38.3 38.3 0.7 0.58 x,y Different letter superscripts indicate tendencies for treatments to differ (p < 0.10); data shown are the least-squared means. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000222 | In human medicine, p53 immunohistochemistry (IHC) is a common method that is used for the identification of tumors with TP53 mutations. In veterinary medicine, several studies have performed IHC for p53 in canine tumors, but it is not known how well it actually predicts the mutation. The aim of this study was to estimate the accuracy of the IHC method for p53 (clone PAb240) using a lab-developed NGS panel to analyze TP53 mutations in a subset of malignant tumors in dogs. A total of 176 tumors were analyzed with IHC and then 41 were subjected to NGS analysis; among them, 15 were IHC positive and 26 were negative, and 16 out of 41 (39%) were found to be inadequate for NGS analysis. Excluding the non-evaluable cases at NGS, of the remaining eight IHC-positive cases, six were mutants and two were wild-type. Among the 17 IHC-negative cases, 13 were wild type, and 4 were mutants. The sensitivity was 60%, specificity was 86.7%, and the accuracy was 76%. These results suggest that when using IHC for p53 with this specific antibody to predict mutation, up to 25% wrong predictions can be expected. accuracy canine tumors immunohistochemistry NGS p53 sensitivity specificity TP53 tumors This research received no external funding. pmc1. Introduction TP53 is a well-known tumor suppressor gene that encodes the p53 protein, which is involved in cell cycle arrest in damaged cells that require DNA repair or, in cases of damage beyond repair, triggering apoptosis. Immunohistochemical detection of p53 is used in daily practice as a surrogate marker of mutation in various human cancers . However, there are conflicting opinions regarding the reliability of IHC to detect p53 anomalies. Mutant p53 protein has a significantly longer half-life and greater stability than its wild-type counterpart and is, therefore, detectable by immunohistochemical methods . It is reported that missense mutations lead to the production of a non-functional protein with a longer life span and is thus detected by IHC as strong and diffuse nuclear staining . In humans, it is reported that the majority of TP53 mutations are missense substitutions (75%) . On the contrary, there are null mutations or non-sense mutations that lead to no p53 protein expression at all, and this is reflected by a complete absence of immunostaining . Moreover, it is now known that certain types of mutations, such as truncating mutations, do not result in protein stabilization . Furthermore, it appears that wild-type p53 can also be stabilized in the absence of mutations, for example, with heat, oxidative stress, irradiation, or chemotherapeutic agents . Nevertheless, many studies in human medicine have validated the use of IHC for p53 to identify cases with mutations of the TP53 gene . Therefore, while IHC is a useful, cost-effective, and rapid tool to detect p53 accumulation, further analysis by gene sequencing is needed to confirm the mutational status in canine species and to correlate it with the biological behavior and prognosis of tumors. In the canine species, for which many studies are based on immunohistochemistry alone, altered p53 immunoexpression has been reported in different tumors, such as cutaneous hemangiosarcomas , mammary carcinomas , osteosarcomas , liposarcomas , mast cell tumors , squamous cell carcinomas , transmissible venereal tumors , prostate cancer , and epithelial colorectal tumors . Different monoclonal and polyclonal antibodies were used in these studies, and they had conflicting results in terms of both the extent of positivity and the correlation with prognosis. In a study by Zacchetti et al. (2007) on canine tumors, the authors compared the immunohistochemical expression of p53 with its mutational status in 6 sarcomas and 21 mammary carcinomas using six anti-p53 antibodies, then they compared the results with those of DNA analysis. Only the monoclonal PAb240 and PAb421 and the polyclonal CM1 antibodies were able to detect the expression of the canine p53 protein. CM1 had the highest concordance between positive expression of p53 protein by IHC and presence of a gene mutation, while the concordance of PAb240 was lower . Generally, in both human and veterinary medicine , a 10% cutoff for nuclear immunopositivity is used, but as there is disagreement among authors, where several cutoff values have been used for both humans and dogs . Next-generation sequencing (NGS) can be used to detect TP53 mutations, but this technique has a high working load and high costs. These disadvantages are compensated by the possibility of detecting a wide range of mutations and the high sensitivity of the technique, but due to its high cost, it cannot be used for routine analysis in veterinary medicine. Hence, the aim of the present study was to measure the accuracy of the immunohistochemical method for p53 using NGS (used as a gold standard) to analyze TP53 mutations in different types of canine tumors that were previously tested with IHC with the monoclonal antibody PAb240. Another aim of the work was to apply two IHC positivity cutoff values to identify which one would correlate better with NGS results. 2. Materials and Methods 2.1. Case Selection, Histological Classification, and Grading The study was based on 176 canine tumors that were identified in the archives of the Anatomic Pathology Section of the Department of Veterinary Medical Sciences of the University of Bologna and the Anicura Veterinary Hospital "I Portoni Rossi", Bologna, Italy, for which formalin-fixed paraffin-embedded (FFPE) specimens were available. Samples included 89 mammary carcinomas, 23 squamous cell carcinomas (SCCs), 19 soft tissue sarcomas (STSs), 19 amelanotic melanomas from skin and oral mucosa, 22 mast cell tumors, and 4 osteosarcomas. Whenever possible, we selected cases with the highest histological grades. Hematoxylin and eosin histological sections were reviewed by 2 board-certified authors (BBr, LM) until a consensus diagnosis was reached, and cases were classified according to the most recent classification and histological grading . 2.2. Immunohistochemistry Immunohistochemistry for p53 was performed in each case on 3 mm thick slides following a previously described method using a monoclonal antibody (clone PAb240, 1:200 dilution; BD Pharmigen). Cases were considered positive if >10% of the neoplastic cells displayed nuclear positivity, and cases with >50% neoplastic positive cells were recorded. Sections of canine mammary carcinoma in which the expression of p53 was known were used as positive controls. The PAb240 clone recognizes both wild-type and mutated TP53, and its cross-reactivity with canine tissues has already been demonstrated . 2.3. Next-Generation Sequencing (NGS) All immune-positive cases and 26 negative cases were analyzed with NGS. Sequencing with NGS was performed at the Molecular Pathology Laboratory of the Policlinico Sant'Orsola-Malpighi, Bologna, Italy. For each paraffin block, only tumor areas with a greater tumor cellular component were selected, avoiding non-tumor areas, necrotic areas, and areas rich in stroma. This selection was made by observing the slide under a microscope and selecting the areas to be removed from the paraffin block with a marker. Obviously in cases such as mammary comedocarcinoma in which the necrotic areas are closely associated with the tumor parenchyma, this was note possible. DNA was extracted from two to three 10 mm thick tissue sections, which were scratched manually with a sterile blade from two or three sections, depending on the amount of neoplastic tissue present. DNA extraction was performed using 50-70 mL of Quick Extract FFPE Kit (Lucigen, LGC Biosearch Technologies, Hoddesdon, UK) in order to allow the melting of paraffin and the degradation of cellular components. DNA was quantified using a Qubit 1.0 fluorometer (Thermo Fisher Scientific, Waltham, MA, USA), according to the manufacturer's recommendations. DNA was amplified using a laboratory-developed NGS panel (Molecular Pathology Laboratory of the Policlinico Sant'Orsola-Malpighi). The panel was designed using the Ion AmpliSeq Designer Tool (Thermo Fisher Scientific) and allowed amplification and sequencing of all the coding sequences (CDSs) of the TP53 gene (start chr5:32560598, end chr5:32565670; reference: Canis lupus familiaris 3). The panel included a total of 48 amplicons between 125 and 175 bp in length. A total of 30-40 ng of DNA was used for library amplification, using the AmpliSeq Plus Library Kit 2.0 (Thermo Fisher Scientific, Waltham, MA, USA). Briefly, 2 pools of the same sample were merged together and 2 mL of FUPA enzyme was added. At the end of the digestion step, 4 mL of Switch Solution, 2 mL of IonCode, and 2 mL of DNA ligase were added. A total of 45 mL of magnetic beads (AMPure, Beckman Coulter, Brea, CA, USA) were added to 30 mL of indexed libraries (beads/libraries = 1.5). The samples were then incubated on a magnetic plate for 5 min and washed with 150 mL of 70% ethanol. Finally, the samples were eluted with 50 mL of tris-EDTA. Quantification of the libraries was carried out by real-time PCR using a Quantitative IonQuant kit (Thermo Fisher Scientific, Waltham, MA, USA). The calibration curve was generated using E. coli DNA at concentrations of 6.8, 0.68, and 0.068 ng/mL. Amplicon libraries were diluted to 1:100 and quantified using the Ion TaqMan(r) Assay (Thermo Fisher Scientific, Waltham, MA, USA). Finally, the samples were diluted to a final concentration of 22 pM and loaded on the IonChef machine in a single pool for the emulsion PCR step. The sequencing was performed using the GeneStudio S5 Sequencer (Ion 530TM Chip) and the results were analyzed using Integrated Genome Viewer software (IGV v2.9.2, ). To avoid false positive results, only the nucleotide variants with a variant allele frequency (VAF) higher than 10% of the total number of analyzed sequences were used for the mutational call. The functional interpretation of the mutation was evaluated using the PolyPhen2 tool ) PolyPhen-2 score is a tool which predicts the possible impact of an amino acid substitution on the structure and function of a protein. 2.4. Statistics Accuracy was evaluated based on sensitivity, specificity, and predictive values using diagnostic testing accuracy . The accuracy of IHC compared to NGS was evaluated by calculating the sensitivity, specificity, and predictive value (and their 95% confidence interval (CI) . When a mutation of TP53 was detected, samples were considered true positives; on the contrary, wild-type TP53 samples were considered true negatives. Therefore, IHC-positive samples with wild-type TP53 were considered false positives, and samples with TP53 mutation and negative IHC were considered false negatives. Furthermore, differences in the percentage of immunoreactivity in IHC between wild-type and mutated TP53 were investigated with the Mann-Whitney test and by fitting an ordered logistic model. IHC immunoreactivity was evaluated based on 3 classes: <10%, >=10-50%, and >=50%. p-values < 0.05 were considered significant. Statistical analyses were carried out using STATA 17.0 statistical software (StataCorp, College Station, TX, USA). 3. Results 3.1. Histopathology and Grading A total of 89 cases of mammary carcinomas were classified as follows: 15 tubular carcinomas, 11 papillary carcinomas, 11 tubulo-papillary carcinomas, 18 solid carcinomas, 6 comedocarcinomas, 9 complex carcinomas, 5 ductal carcinomas, 6 mixed carcinomas, 1 adenosquamous carcinoma, 2 micropapillary carcinomas, and 5 intraductal carcinomas. Among them, 28.09% were Grade 1, 32.58% were Grade 2, and 31.46% were Grade 3. Among the 19 soft tissue sarcomas, 11 (57.89%) were Grade 2 and 8 (42.10%) were Grade 3. Among the 22 mast cell tumors, 5 were high grade (22.72%) and 17 were low grade (77.28%). The 23 squamous cell carcinomas, 19 amelanotic melanomas, and 4 osteosarcomas were not graded. 3.2. Immunohistochemistry Of the 176 canine tumors that were examined, only 15 (8.52%) were positive for p53 by immunohistochemistry. The three positive cases were mammary carcinomas (3.37% of 89 cases), of which one was a solid Grade 2 carcinoma, and two were Grade 3 comedocarcinomas . A total of six positive cases were squamous cell carcinomas (26.08% of 23 cases) , and three cases were soft tissue sarcomas (15.78% of 19 cases) , of which two cases were Grade 2 and one was Grade 3. There were two oral amelanotic melanomas (10.52% of 19) and one high-grade mast cell tumor (4.54% of 22 cases) that were positive. Osteosarcomas were all negative. Of the total positive cases, 11 had more than 50% positive cells and 4 had 10-50% (Table 1). 3.3. Next-Generation Sequencing (NGS) For the following scientific work, only the p53 panel was considered and was designed for all TP53 CDS from exon 1 to 10, therefore, it was expected to detect almost all possible protein domains. Exons 9 and 10 have lower coverage (less than 150x) in terms of "reads", therefore, any mutations on these exons may be undetectable. For the sequencing, 15 IHC-positive samples were selected and 7 of them (46.66%) were found to be non-evaluable due to high DNA degradation. Of the immune-negative cases, 9 out of 26 (34.6%) were non-evaluable. The non-evaluable (inadequate) cases were mostly mammary (10/18, 55.55%) and cutaneous (3/14, 21.42%). Following the analysis, two samples were wild-type (2/8, 25% false positives), while at least one mutation was identified in the remaining six samples (6/8, 75% true positives). Among the six mutated cases, three had single mutations, one had two mutations, and two had three p53 mutations. There were ten different types of mutations that were found; all were missense mutations except two cases, which had an identical non-sense mutation (Table 1). Furthermore, 26 IHC-negative cases were randomly selected among the tumors with the highest histological grade. A total of nine of these were non-evaluable (9/26, 34.6%). Among the remaining 17 samples, 13 were wild-type (76.47%) (Supplementary Table S1) and 4 had single mutations (23.52%), specifically 3 missense and 1 non-sense mutation (Table 2). The non-sense mutation was the same as the two true positive cases with non-sense mutation. 3.4. Statistics The accuracy results are reported in Table 3 and Table 4 and Scheme 1. Table 3 and Graph 1 show the results of p53 immunopositivity at values equal to or greater than 10%, while Table 4 shows the results that were obtained by setting the immunopositivity threshold to values equal or greater than 50%. The Mann-Whitney test results suggest a significant difference for IHC-positive cell classes between wild-type samples and samples with mutations (p-value = 0.0354). Furthermore, the ordered logistic model suggests an effect of the presence of mutations on the IHC-positive cell classes (OR = 8.9, 95%CI: 1.3-60.2) and a larger probability of mutation in IHC classes with immunoreactivity >=10% than in classes with immunoreactivity <10%. 4. Discussion TP53 is the most frequently mutated gene in human cancers, and its mutation affects about 50% of human malignancies, mainly in the form of missense mutations . In our series, the cases that were positive on immunohistochemistry accounted for 8.52% of the total number of analyzed cases. Based on tumor types, 3.37% of p53-positive cases were in mammary carcinomas, 26.08% in squamous cell carcinomas, 15.78% in soft tissue sarcomas, 10.52% in amelanotic melanomas, and 4.54% in mast cell tumors. As expected, these percentages are lower compared with data using a polyclonal antibody . In fact, previous studies that used polyclonal CM-1 antibody showed positivity in 22% of canine lymphomas , 37.5% of squamous cell carcinomas , and 44% of colorectal epithelial tumors . By contrast, immunohistochemical analysis with the polyclonal FL-393 antibody on canine cutaneous mast cell tumors showed only 17/71 p53-positive cases (23.94%). Studies in which monoclonal antibodies were used had lower positivity percentages, as these antibodies are more specific but less sensitive. In our previous study on 170 canine mammary carcinomas with PAb240, we found 4.7% positivity ; to confirm these data, in the present work on a different series of canine mammary carcinomas, we had similar positivity of 3.37%. A similar study on mammary carcinoma found 7 out of 35 positive cases (20%) . The polyclonal CM-1 antibody has also been employed in canine squamous cell carcinomas, showing p53 expression in 37.5% of cases , higher than the 26.08% in the present study. The lower percentages in our study may be due to different reasons: the use of different antibodies (monoclonal or polyclonal), the scoring method, or the pre-analysis variables. To date, only a few studies have compared the concordance between different clones of p53 antibodies and the presence of mutations . In a study by Zacchetti et al. (2007) , six monoclonal antibodies and one polyclonal antibody were tested in six sarcomas and 21 mammary carcinomas from 27 dogs, and the results were compared with the gene mutation analysis. The monoclonal PAb240 antibody was able to detect the expression of canine p53 protein with gene mutation with a concordance of 45.45% (5/11). As previously mentioned, CM1, which is polyclonal, was found to give the highest concordance (8/11). Currently, in human medicine there is no consensus as to which antibodies are most appropriate for evaluating mutation-associated p53 expression. In our study, the positivity of a small number of tumors allowed subsequent NGS analysis of a small number of cases. This was mostly due to the high degradation of FFPE tissues, which resulted in 16 inadequate samples (39% of cases sequenced). This obstacle is acknowledged in an article by Ihle et al. (2014) , which noted that one of the difficulties of PCR-based amplification methods is the fixation artifacts of FFPE samples. These artifacts seem to be due to post-mortem phenomena, including the deamination of cytosines and adenines, which result in uracil residues and hypoxanthine, respectively. The DNA contained in formalin-fixed tissue undergoes alterations with chemical modification and fragmentation, and this makes it difficult to obtain samples that are suitable for molecular analysis. Following NGS analysis, we compared the NGS and IHC methods applying a >=10% positivity threshold, and calculated a sensitivity of 60% and a specificity of 86.7%, with a total accuracy of 76%. These values are similar to those that were reported in human medicine, with concordance between p53 IHC and TP53 mutation status ranging from 55 to 89% in human gliomas (Grade I-IV) . Moreover, in the same studies, the false-positive rate (the incidence of p53 IHC positivity with the presence of wild-type TP53) ranged from 2 to 45%. One study on human glioblastomas found 66% true positives, which are similar to the results of the present study . In addition, another study found 6026/7878 IHC-positive cases (76.5%) with TP53 mutations in different human cancers . As shown in Table 3, the positive predictive value was 75% (95%CI 34.9-96.8%) using a >=10% threshold for p53 IHC positivity, with a corresponding false positive rate of 25%. This percentage can be explained by the antibody clone (PAb240), which does not discriminate between wild-type and mutant p53 proteins. In fact, false positivity occurs in cases where wild-type TP53 is either overexpressed or exhibits a prolonged half-life. There are several recognized causes of half-life prolongation, such as heat, oxidative stress, irradiation, and chemotherapeutic agents . The two false positive cases were an SCC (10-50% positivity) and an STS (>=50% positivity). The 50% threshold was applied to verify whether a higher threshold would prevent false positives, but in one case >50% positivity corresponded to wild-type TP53. Mutations were also found in cases that had 10 to 50% positivity, confirming that the 10% cutoff value is reliable. Using a >=50% threshold compared to >=10% does not seem to provide any benefits; in fact, the sensitivity drops by half (30%) even if the PPV is unchanged, the specificity is significantly increased (93%), the NPV drops by 10%, and the accuracy drops by 8%. For these results, the threshold of >=10% is, therefore, considered to be more accurate than >=50%. It is important to note that with the latter threshold, accuracy was moderate (76%); in fact, 25% false positives and false negatives is not a negligible proportion. On the other hand, the Mann-Whitney test and the ordered logistic model suggest that the higher the IHC immunoreactivity percentage, the greater the probability of mutation. Since IHC immunoreactivity was <10% for most cases (15 out of the 25 included in this statistical analysis), a more-in-depth IHC study using a larger case series with a >=10% threshold would be appropriate. The major limitation of the study was the small number of cases that were analyzed; however, it must be noted that the initial number of cases was extremely high, which demonstrates the difficulty of collecting larger amounts of p53-positive tumors. Furthermore, NGS is very expensive and not easily accessible, which are obstacles for current and future studies. Further studies will be needed to truly establish whether IHC for p53 can be a reliable substitute for genetic investigations in canine tumors. In our previous study on canine mammary carcinomas employing the same antibody (Pab240), the few positive cases were in fact related to a worse prognosis. A total of 13 types of mutations were found in this case series (nine TP, three FN, one in both); most of these were missense mutations in both groups. The PolyPhen2 score, which predicts the possible impact of an amino acid substitution on the structure and function of a human protein, was always 1 or very close to 1 in this study, indicating a high likelihood of damage to the protein. A single FN case had a non-sense mutation with a stop codon that probably generated a truncated protein that could not be detected with immunohistochemistry. As discussed earlier, FN cases may be due to the specific monoclonal antibody, because if the mutations are located outside of its binding site, they will not be recognized. Another explanation for the FN results may be the overexpression of MDM2 or CDK2NA homozygous deletions, which can cause degradation of mutant TP53, potentially resulting in a false-negative p53 IHC result . A proportion of FP cases can also be explained by the type of antibody used, as it is known that Pab240 detects both mutant and wild-type p53 protein. In addition, for both FP and FN cases, it must be considered that IHC and NGS are not performed exactly in the same tissue material, hence we assumed molecular homogeneity of TP53 mutations within a given tumor sample. As such, it is conceivable that mutational variability could exist within different sections of the same tumor specimen. Finally, the presence of many non-adequate (NE) cases for NGS was due to the inability to extract sufficient DNA from the FFPE material. This may be due to pre-analysis conditions, such as prolonged formalin fixation, which can be a significant issue in veterinary medicine . This highlights that sampling and fixation of tumor tissues are of critical importance for both immunohistochemical and molecular techniques. 5. Conclusions In this study, immunoexpression of p53 was compared to NGS analysis in order to verify whether p53 immunopositivity can predict TP53 gene mutations. The results suggest that when using IHC for p53 with the specific antibody in this study (clone PAb240, BD Pharmigen) to predict mutation, the sensitivity was 60%, specificity was 86.7%, and the accuracy was 76%, which means that up to 25% wrong predictions can be expected. Moving the IHC threshold to >=50%, the sensitivity was 30%, specificity was 93%, and the accuracy was 68%. Therefore, our results suggest that setting the threshold for the immunohistochemical evaluation of p53 at >=10% is the most appropriate. Supplementary Materials The following supporting information can be downloaded at: Table S1: List of 26 cases negative to p53 immunoistochemistry, showing that 4/26 cases had TP53 mutation by NGS. Click here for additional data file. Author Contributions Conceptualization, B.B. (Barbara Brunetti) and B.B. (Barbara Bacci); methodology, L.V.M., D.d.B. and G.D.; software, G.T.; validation, G.T., F.I. and D.d.B.; formal analysis, F.I.; investigation, B.B. (Barbara Brunetti) and B.B. (Barbara Bacci); resources, B.B. (Barbara Brunetti) and D.d.B.; data curation, F.I. and G.T.; writing--original draft preparation, B.B. (Barbara Brunetti), B.B. (Barbara Bacci) and D.d.B.; writing--review and editing, B.B. (Barbara Brunetti), B.B. (Barbara Bacci) and D.d.B.; visualization, B.B. (Barbara Brunetti); supervision, B.B. (Barbara Bacci); project administration, B.B. (Barbara Brunetti) and B.B. (Barbara Bacci); funding acquisition, B.B. (Barbara Brunetti) and D.d.B. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Informed consent was obtained from the owners of the animals. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Figure, Scheme and Tables Figure 1 Immunohistochemistry of dog anti-p53 antibody. (a) Mammary carcinoma; the majority of the nuclei were immunolabeled (4x). (b) Squamous cell carcinoma; the nuclei were strongly and diffusely immune-positive (20x). (c) Soft tissue sarcoma; about half the cells had an immune-positive nucleus (10x). (d) Amelanotic melanoma; all nuclei of tumor were immunolabeled (10x). animals-13-00899-sch001_Scheme 1 Scheme 1 Cases evaluated with IHC and NGS, considering p53 immunopositivity threshold equal or greater than 10%. animals-13-00899-t001_Table 1 Table 1 Tissue, tumor type, histological grade, immunohistochemical positivity, and TP53 mutation results for each p53-positive case (15/176) are reported. NE, non-evaluable; WT, wild-type; SCC, squamous cell carcinoma; MCT, mast cell tumor; STS, soft tissue sarcoma. Tissue Histotype Grade IHC Class TP53 (Ref. TP53-202) Mutation PolyPhen2 Score Mammary (3) Comedocarcinoma 3 >50% NE - - Solid carcinoma 2 10-50% NE - - Comedocarcinoma 3 >50% NE - - Skin (6) SCC - 10-50% p.C290Y Missense 1 SCC - 10-50% p.Y257F p.R265Stop p.C329F Missense Non-sense Missense 1 1 1 SCC - >50% p.P202L p.P203S p.R265Stop Missense Missense Non-sense 0.969 0.997 1 SCC - >50% p.P193L p.H230D Missense Missense 1 0.993 SCC - 10-50% WT - SCC - 10-50% NE - Skin (1) MCT high 10-50% p.R209S Missense 1 Oral (2) Amelanotic melanoma - >50% p.G318E Missense 1 Amelanotic melanoma - 10-50% NE - Subcutis (3) STS 2 >50% WT - STS 2 >50% NE - STS 1 10-50% NE - animals-13-00899-t002_Table 2 Table 2 p53-negative tumors with <10% positive cells. Only the four cases with TP53 mutations are reported (4/26). SCC, squamous cell carcinoma. Tissue Histotype Grade IHC Class TP53 (Ref. TP53-202) Mutation PolyPhen2 Score Mammary (2/15) Solid carcinoma 3 <10% p.C186Y Missense 1 Comedocarcinoma 3 <10% p.P372S Missense 0.997 Skin (1/5) SCC - <10% p.R265Stop Non-sense 1 Bone (1/1) Osteosarcoma - <10% p.R301P Missense 1 animals-13-00899-t003_Table 3 Table 3 Accuracy results and their 95% CI of TP53 genetic sequencing results versus p53 IHC staining results for >10% labelling threshold. NGS Mutations NGS WT Total IHC P53+ 6 (TP) 2 (FP) 8 PPV 75% (34.9-96.8%) IHC (FN) 13 (TN) 17 NPV 76.5% (50.1-93.2.4%) Total 10 15 25 Sensitivity 60% (26.2-87.8%) Specificity 86.7% (59.5-98.3%) Accuracy 76% (54.9-90.6%) TP, true positive; FP, false positive; FN, false negative; TN, true negative; PPV, positive predictive value; NPV, negative predictive value. Values in parentheses represent lower and upper bounds of 95% confidence. animals-13-00899-t004_Table 4 Table 4 Accuracy results and their 95% CI of TP53 genetic sequencing results versus p53 IHC staining results for >=50% labelling threshold. NGS Mutations NGS WT Total IHC P53+ 3 (TP) 1 (FP) 4 PPV 75% (19.4-99.4%) IHC (FN) 14 (TN) 21 NPV 66% (43-85.4%) Total 10 15 25 Sensitivity 30% (6.7-65.2%) Specificity 93% (68.1-99.8%) Accuracy 68% (46.5-85.1%) TP, true positive; FP, false positive; FN, false negative; TN, true negative; PPV, positive predictive value; NPV, negative predictive value. Values in parentheses represent lower and upper bounds of 95% confidence. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000223 | Compared with the history of seals in the Baltic Sea, the porpoise has received much less research attention. The harbor porpoise (Phocoena phocoena) has been quite rare in the eastern Baltic in recent centuries, but according to archaeological finds, its population was quite numerous here ca. 6000-4000 years ago (ca. 4000-2000 cal. BC). This paper deals with all known archaeological assemblages of porpoise so far discovered in the eastern Baltic (Estonia, Latvia and Lithuania), discusses the hunting strategies and studies the exploitation of this small cetacean by the Neolithic hunter-gatherers. Fauna historical aspects include new archaeological data in addition to those published previously. We consider whether these new data change the temporal and spatial pattern of porpoise hunting and examine how, in addition to the expected use of porpoise meat and blubber, the porpoise's toothed mandibles were used for patterning ceramics. harbor porpoise eastern Baltic Sea Neolithic ceramics Littorina Sea Estonian Research CouncilPRG29 Latvian Council of Sciencelzp-2021/1-0119 This research was funded by the Estonian Research Council, grant number PRG29 ("Foreign vs. local in the eastern Baltic Medieval and Modern Age foodways: tracing the changing food consumption through the provenance analysis") and the Latvian Council of Science, grant number lzp-2021/1-0119 ("Skills in synergy, crafts in context: an integrated study of eastern Baltic Stone Age technologies"). pmc1. Introduction The harbor porpoise (Phocoena phocoena Linnaeus, 1758) is one of the world's smallest cetaceans. As the name indicates, it stays close to coastal areas and is, thus, particularly visible to people interested in whale watching. The porpoise can swim up rivers and be found hundreds of kilometers from the sea. However, marine coastal waters constitute its most common environment, and the porpoise is a widespread species in cooler coastal waters of the Northern Hemisphere. In the eastern North Atlantic, the harbor porpoise is distributed along the coast of the Barents Sea, the west coast and fjords of Norway, the coasts of Iceland and the British Isles, in Danish waters and along the West European coast as far as north-western Africa . Our main interest is in its distribution in the Baltic Sea, and more specifically, its distribution in the eastern Baltic Sea, with an almost freshwater environment. Not that porpoises avoid freshwater as such, but the environment seems to be unsuitable for permanent habitation by this species. The reason is most probably the shallowness of the littoral zone, which this pelagic species does not like, and severe ice conditions in winter . The Baltic population of porpoise is not large nowadays. The population inhabiting the Baltic Proper has been classified as 'critically endangered', on the basis that the current population is likely to be fewer than 250 individuals . Some decades ago it was estimated that a maximum of 600 individuals occurred in the Baltic, mainly in the southern part of the sea . However, various studies and examinations of sighting and stranding data support the general view that numbers of harbor porpoises in the Baltic Sea have declined and that the distribution range has narrowed . Although studies of mitochondrial DNA and microsatellites show that the Baltic population of porpoises forms a separate geographical unit , the (seasonal) migrations between the Baltic and Kattegat/North Sea still exist. As there is no difference in the isotopic (13C) signature of the porpoises in the Baltic and the Kattegat/Skagerrak, migration between these areas is evident . Despite the low number of porpoises today, this species seems to have been a much more abundant inhabitant in the Baltic in the past. In the coastal waters of Estonia, Latvia and Lithuania, cetaceans have been rare visitors rather than permanent inhabitants. This applies to porpoise as well as other cetacean species (at least, the four species registered). Only recently, in September 2008, white-beaked dolphins (Lagenorhynchus albirostris Grey, 1846) were seen as far east as Tallinn Bay in northern Estonia. On 1 June 2020 a couple of dolphins (most probably bottlenose dolphins) were encountered in Kopli Bay (photographed by the captain of the boat Indrek Sulla), and a humpback whale (Megaptera novaeangliae Borowski, 1781) was seen off the coasts of Poland and Finland. Probably the same individual was finally found dead close to Skulte harbor on the Latvian coast of the Gulf of Riga in July 2006 (information from local newspapers). Older records provide more evidence of the presence of whales in the eastern Baltic. Besides humpback whales, white whales (Delfinapterus leucas Pallas, 1776) are also mentioned . The porpoise, which has permanently inhabited the Baltic for several millennia, can likewise be considered a very rare visitor in the eastern Baltic Sea today: only one or two proven observations per decade are known. It was not like this in the past. In the late 19th and early 20th century, the porpoise was encountered more regularly here (p. 487), (pp. 56-57), (p. 168). In the 1920s and 30s, the porpoise often made it into the newspapers: Ivar Jussi (in Ohtuleht, 29 September 2012) concluded that there are ca. 40 mentions from this period in Estonia, the best known being a picture of "fishermen from Virtsu with a strange fish" . In the Middle Ages and Early Modern Era, the porpoise (merswyn) is mentioned in accounting books among other animal products sold in Tallinn's markets (p. 9). The archaeological record of that period includes only one vertebra of porpoise, found in a mixed layer at 6A Tatari Street, Tallinn (identified in 2022). It seems that porpoise was more like an exotic import in towns of the eastern Baltic at that time, rather than being hunted by local people. In comparison with the history of seals in the Baltic (and references therein), especially the history of the harp seal (Phoca groenlandica Erxleben, 1777), the porpoise has received much less research attention. It has been considered as part of the hunted fauna in zooarchaeological studies, but has not been the subject of any special research in taphonomy. Even though the species has been quite rare in the last centuries, according to archaeological finds, its population was quite numerous ca. 6000-3500 years ago. Thus far, only one paper has summarized the post-glacial spatiotemporal distribution of porpoise in the Baltic Proper , but with insufficient data on porpoise finds from the eastern Baltic. An investigation by Aaris-Sorensen et al. focuses on finds of all cetaceans, but is geographically limited to the southern Scandinavian coast. Data on finds from the eastern Baltic are scattered in reports and papers having some other focus. Figure 1 Fishermen with a strange fish in Virtsu, West Estonia, in 1939. Photo from the Virtsu Hobby Museum--VHM-F0441 . This paper focuses on the archaeological finds of porpoise discovered in the eastern Baltic--Estonia, Latvia and Lithuania--and traces the faunal history of this species as well as its exploitation by humans, covering the period from the saline stage of the Baltic Sea (Littorina Sea) up to the brackish water (Limnea Sea, modern) stage. In cultural terms, the period under consideration corresponds to the New Stone Age or Neolithic. The exploitation of porpoise involved the use not only of hunting products for food but also of bones for practical purposes. Thus, the porpoise mandible with teeth still in place was widely utilized as a tool for decorating pottery. 2. Zooarchaeological Material Our study material for clarifying the history of the porpoise comes from archaeological contexts, as no finds of porpoise from geological contexts are known in Estonia, Latvia or Lithuania. Most of the material has been excavated and collected manually from Neolithic dwelling sites situated on islands, in addition to finds from coastal areas of the mainland , and is dated roughly to the time span 4000-2000 cal. BC. Porpoise has been identified in the archaeological material of Kunda Lammasmagi by Johannes Lepiksaar , at Riigikula I and III, Naakamae and Loona by Kalju Paaver , and in Tallinn (1 Vabaduse Sq.) and at Kopu XI, Riigikula IV and Silinupe by Lembi Lougas . Data on finds from Sventoji have been published by Linas Daugnora . The Naakamae and Loona bones have been re-examined by Lougas, since no anatomical division is given in Paaver . The taxonomic and anatomical determinations were performed using comparative skeletal collections and skeletal atlases. In addition, quantitative methods such as the number of identified specimens (NISP) and the minimum number of individuals (MNI) have been used in most cases (Table 1). Since mainly the vertebrae and/or vertebral bodies have been found, the MNI is not always counted, as the vertebrae assemblages provide no certainty as to the number of individuals present. From the Lammasmagi site at Kunda, which is considered mainly a Mesolithic site, at least one find of porpoise is recorded (thereafter Lougas ). However, it is not clear which bone this was, and the bone is not accessible or else has been lost from the collection. A brief report by Kalju Paaver (held in the archive of the Archaeological Research Collection, Tallinn University), which includes the results of animal bone identifications based inter alia on the material found at Kunda Lammasmagi in the 1930s, makes no mention of porpoise. Perhaps the find had already been lost by that time. An inventory of bone collections in 2022 did not clarify the existence of the porpoise find either. Thus, some doubt remains as to whether there was any porpoise at the site at all. The Mesolithic context of the site does not support the existence of a porpoise find there, but as has been ascertained earlier, Neolithic finds were also found at the Kunda Lammasmagi site, as confirmed by 14C (radiocarbon) dates, and both Narva and Comb ceramics have been recorded . However, because of the uncertainty, this porpoise record will not be discussed further. The most exceptional material in terms of porpoise bones come from the Neolithic site of Naakamae on Saaremaa Island in western Estonia. Here, a huge quantity of marine mammal remains were found in the 1960s. Although the material is dominated by harp seal, porpoise was also intensively hunted . At Naakamae, all body parts (skull fragments, vertebrae and limb bones) are represented in the zooarchaeological material, but only four fragments of mandibles are present. The Loona site is situated quite close to Naakamae, but is somewhat younger according to the archaeological context and 14C dates . Here, a huge amount of cod and seal bone was found. However, porpoise is represented by two vertebrae only . North of Saaremaa, another island--Hiiumaa--has also yielded a few porpoise bones. Many seal hunters' campsites are known on Kopu, the westernmost peninsula of Hiiumaa . The Neolithic site Kopu XI, situated in the southern part of the ancient Kopu Island, is similar to Naakamae and Loona, but in contrast to the Saaremaa sites, the bone material is very fragmented and most of it is burnt. Such preservation makes it difficult to identify bones for taxonomic purposes. However, there are five fragments of porpoise skeleton: burnt temporal bones (i.e., bulla tympanica), the hardest part of the skull, which preserves better than other bones of the skeleton. In addition, one unburnt fragment of a vertebral disk may come from a young porpoise, but this assumption is based on the disk's structure rather than its shape. Namely, the porpoise, like other cetaceans, has a special bone structure, which differs from that of terrestrial mammals. However, as the disk fragment is quite small, some doubt may still remain as to whether it comes from the seal or porpoise (Kopu XI finds were re-examined by Lougas in 2022). Two Neolithic sites on the coast of the mainland--Tallinn Vabaduse Sq. (Estonia) and Silinupe (Latvia)--are similar in terms of their geographical location and faunal evidence. Both are situated at the southern shore of a bay close to a river estuary and, besides terrestrial animals, have yielded considerable amounts of harp seal and porpoise bone . It is worth mentioning that only one ca. 6 cm fragment of a mandible is recorded at the Vabaduse Sq. site, and none at Silinupe. The mentioned geographical locations correspond to the old hunting method of driving the migrating porpoises into narrow and shallow bays, where hunters can slaughter them . The other sites considered here, Riigikula I, III and IV in north-eastern Estonia and Sventoji 2B and 3B in western Lithuania, are not very rich in porpoise bones . Only a few vertebrae have been found, although the hunting of harp seal was apparently also practiced by the settlers of Riigikula and Sventoji. The Riigikula finds are important, since they prove the occurrence of porpoise as far as the eastern part of the Baltic Sea, in the eastern Gulf of Finland. There is also one lumbar vertebra of porpoise from Tallinn found in mixed layers of medieval/modern age at 6A Tatari Street. In the absence of 14C dates, it does not provide definite confirmation of the occurrence of porpoise in the mentioned period. Thus, 6A Tatari Street is not far from the Vabaduse Sq. site (ca. 200 m), where the Stone Age finds are partly mixed with the medieval and early modern finds. Although Stone Age layers are absent in Tatari Street, a few finds indicating the Stone Age are known in the vicinity . Currently, in the absence of 14C dates and according to the archaeological context, we can relate this porpoise find to the medieval and/or modern period. 3. Porpoise Tooth Impressions as Decoration on Pottery In addition to the faunal remains testifying to the porpoise's importance as a source of meat and blubber for coastal communities in the Neolithic, a recent study has revealed that porpoise hunting also yielded a tool used to create a distinctive kind of pottery decoration. As described by Berzins and Dumpe , the elongated comb-like impressions consisting of a row of fine lenticular pits , previously documented as "fine teeth" or as a special kind of comb decoration , are, in reality, impressions made with a row of porpoise teeth. Experiments using a harbor porpoise mandible demonstrated convincingly how such impressions could be achieved using one half of the porpoise mandible. The ramus of the mandible provides a convenient handle, and a stamp with the desired number of teeth could be prepared by simply removing the superfluous teeth from the mandible. Since the dentition of the porpoise differs radically from that of all other members of the region's fauna, there is no possibility of confusion with tooth impressions of other animals. In cases where the imprints are clear, they may be unequivocally distinguished from impressions made with, for example, a denticulated shell edge or some other specially prepared stamp. The row of tooth imprints may be straight or somewhat curved. In general, the orientation of the long axis of individual tooth imprints tends to follow the overall direction of the row of imprints, although in many cases, individual teeth are somewhat obliquely oriented. In cases where a row of somewhat obliquely oriented porpoise teeth has been used to make a relatively deep imprint in the clay, it may resemble a cord impression; however, in such cases, the tooth imprints will be deeper than imprints left by windings of cord. In cases where the stamp has made a shallow impression, there will be short linear marks left by the tips of the teeth, whereby the overall impression of the stamp resembles a "dashed line" . Porpoise tooth decoration was first recognized on pottery from the Sarnate site, near the open-sea coast of north western Latvia, and has since been documented in the pottery assemblages from a number of eastern Baltic coastal habitation sites dated to the final part of the Stone Age. These include sites on the western shore of the Gulf of Riga (Gipka A and B, lower layer of Purciems C) and at the head of the gulf (Silinupe and Slocene), all in present-day Latvia, as well as the above-mentioned Estonian sites of Vabaduse Sq. and Naakamae . The pottery with porpoise tooth impressions from Latvia's coastal belt is classed as Early Sarnate Ware. Five 14C dates from Silinupe indicate a time span of 3640-2935 cal. BC for the Early Sarnate Ware phase at this site, which has also yielded abundant faunal remains of porpoise . Three dates from dwellings with Early Sarnate Ware at Sarnate itself give an interval of 3516-2880 cal. BC . One 14C date has now also been obtained for the lower layer of Purciems dwelling C, which has likewise produced Early Sarnate Ware, indicating the time interval 3636-3382 cal. BC (wood charcoal from the 1936 excavation; 4761 +- 30 BP; FTMC-UM96-6; 95.4% probability). The Vabaduse Sq. and Naakamae sites in Estonia yielded pottery classed as Typical Comb Ware and Late Comb Ware . The 14C dates from these two sites place them in the time interval 3300-2800 BC . Although ceramics from Estonian coastal sites have been thoroughly studied, experiments to replicate the impressed decoration have only been carried out using a specially made comb-like tool. Comprehensive study has been undertaken on the pottery from Sarnate, Silinupe and Rinnukalns. Porpoise tooth decoration is found on the exterior of 28% of the separate vessels identified from rim sherds recovered from dwellings of the Early Sarnate Ware phase at Sarnate, and on 9% of the vessels from area 7 at Silinupe (Table S1). The porpoise tooth stamp impressions in the Sarnate assemblage have an overall length of up to 29 mm, with imprints of four to eight individual teeth; at Silinupe, the overall length reaches 23 mm, with imprints of four to eight teeth. The pottery with decoration now identified as porpoise tooth, classed as belonging to Early Sarnate Ware in Latvia and to Late Comb Ware in Estonia , is viewed as manifesting a fusion of the Narva tradition of pottery-making, represented in the eastern Baltic already before 5000 cal. BC, and the Comb Ceramic tradition, which had spread to the region from the north-east at ca. 4000 cal. BC (pp. 40-41), . The pottery with porpoise tooth decoration, used primarily for cooking (p. 142), generally has a porous fabric with lamellar voids remaining from shell temper that has been leached away . The designs on vessel exteriors made with porpoise tooth stamps include horizontal rows of vertically or obliquely oriented impressions, rhombuses, herringbone patterns and zigzags, sometimes in combination with shallow pits . These designs essentially belong to the decorative repertoire of Comb Ceramics, the porpoise tooth stamp being utilized in place of a comb or cord stamp. Considering that the porpoise could only have been hunted at the coast and along the lower courses of rivers, a very significant discovery is the occurrence of porpoise tooth impressions also on pottery from inland sites; it has been found at Rinnukalns, located at the outlet of the River Salaca from Lake Burtnieks. At this site, 95 km upriver from the coast, porpoise tooth decoration occurs on the exteriors of 6% of the vessels assigned to the phase of midden accumulation (Table S1), dated to 3400-3200 cal. BC . A number of pottery sherds with such decoration are also known from approximately contemporaneous ceramic assemblages in the area around Lake Lubans , which would have been reached from the coast by traveling more than 200 km up the Rivers Daugava and Aiviekste. In this intensively researched area, porpoise tooth impressions have so far been identified on four sherds from Malmutas griva , two sherds from Piestina and 14 sherds derived from at least three vessels in the assemblage from Sulka. In all cases, porpoise tooth decoration occurs on pottery with characteristic lamellar pores indicative of shell temper. In this inland region, porpoise tooth is rarely encountered in comparison with other stamp forms, although it may be somewhat more common than it appears to be, because secure identification is not possible in the case of weathered or degraded sherds. As far as can be ascertained from the highly fragmented material, the designs executed in porpoise tooth stamps on the pottery vessels found at inland habitations resemble those seen on pottery from coastal sites. Various other similarities to the coastal pottery, such as the occasional occurrence of knot, plait and beaver metapodial impressions, indicate that some of the pottery occurring on the inland sites was made by people whose pottery-making techniques corresponded to those of the inhabitants of the coastal belt. 4. Discussion 4.1. The History of the Porpoise in the Eastern Baltic Sea According to Sommer et al. , the harbor porpoise is first encountered on the southern Baltic settlement sites of the Maglemose and Kongemose Cultures, i.e., ca. 7600-5000 cal. BC. However, as the opening of the Danish Straits and the inflow of saline water into the Baltic Proper took place after 7000 BC , porpoise could spread to the Baltic only after this geological event. Unfortunately, most of the early finds of porpoise considered in Sommer et al. were dated according to the archaeological context and not by using direct 14C dating (as in our study). The only exception seems to be a porpoise from the Stora Forvar site on the island of Gotland, Sweden, which has been dated to ca. 4080 cal. BC. This seems to be in accordance with the dates of the first harp seals found on Baltic settlement sites . Both species appear on the Neolithic settlement sites of the eastern Baltic approximately at the same time, and on all the sites where bones of porpoise were recorded, harp seal occurs in higher numbers. In the eastern Baltic, the Riigikula site provides the oldest archaeological context with porpoise bone finds, relating to the Narva and Typical Comb Ware cultures, i.e., ca. 4000 cal. BC . The association of the porpoise finds with the dated material is not very certain, and more evidence, such as a direct 14C date, is needed. The highest number of bones of this cetacean relates to the time span 3400-3000 cal. BC (Late Comb Ware, Early Sarnate Ware). This coincides with the period of highest salinity in the Baltic , probably offering a suitable environment for marine fauna. The abundance of porpoises in the eastern Baltic diminished after 3000 BC, when the salinity in this sea also decreased, since the outflow of brackish Baltic Sea water became more intense than the inflow of saline water from the Atlantic, and subsequently the visits by this small cetacean became rare. This assumption is also based on the evidence of faunal material from the Asva and Ridala sites (ca. 800-500 BC) on Saaremaa Island, where intensive seal hunting took place but no porpoise bones have been found so far . Certainly, more 14C-datings of porpoises are needed from the Baltic region in order to trace the history of the harbor porpoise in this sea. 4.2. The Role of the Porpoise in Human Lifeways In the middle and second half of the 4th millennium BC, porpoise tooth decoration came to be commonly applied on pottery in the eastern Baltic region. One half of the porpoise mandible, with its long, straight row of teeth, could be modified with minimal effort so as to furnish a pottery stamp comparable in length and width to the comb stamps that had already been very widely used to decorate pottery in the region for several centuries before this. Hence, impressed decoration with porpoise teeth could readily be accommodated within the established design grammar of pottery ornamentation, the porpoise tooth stamp taking the place of the comb stamp. However, we may also ask--given the porpoise's economic importance for certain coastal communities in this period--whether the stamping of pottery with an instrument fashioned from part of this animal also had a special meaning related to the animal's salience in the consciousness of the pottery-makers. There is practically no other evidence to suggest that the porpoise held a prominent position in the world-view of the Neolithic people in this region. In contrast to the large number of terrestrial mammal and bird representations in the form of figurines and zoomorphically carved artefact parts , so far, just one piece has been interpreted as a representation of a porpoise. This is a 36 mm long clay figurine from the north Estonian site Jagala Joesuu V, which appears to display characteristic porpoise features, notably the dorsal fin . In connection with this, we may note that the other marine mammals hunted in the region, namely seals, are likewise virtually absent from mobiliary art. On the other hand, seals are quite commonly represented by the use of their teeth for making tooth pendants, as found in graves at the Zvejnieki cemetery (pp. 83-89), (pp. 144-145), whereas the excavated burials in the eastern Baltic have not yielded any body parts of porpoise. It may actually be that decoration on pottery served as the main medium for expressing the value that coastal communities attached to the porpoise. Because of the distinctiveness of this animal's teeth and the imprints obtainable from them, such a message could be conveyed quite unambiguously. It is also possible to delineate the range of mental associations that the porpoise could have had. In the first place, of course, it would have been connected with the coastal and river-mouth environments that it inhabits. Further, the historical record indicates that a very important method of porpoise exploitation was mass hunting by coordinated drives, involving several boat crews with nets, as on the coast of Denmark, for example . If similar collective methods were being employed in antiquity, then the joint endeavors of porpoise hunting must have been significant for the formation and maintenance of social groups among the inhabitants of the coastal belt. Consequently, the porpoise may have had strong associations with coastal group identity and collective activities. A sense of seasonality must also have featured prominently in the perception of the porpoise among the communities involved in hunting it, given that the animal was present and accessible to hunters in the region only in summer. The warmer part of the year also offered the best conditions for pottery-making (vessels could be dried more quickly for firing), and, thus, the seasonal concurrence of the two tasks may have been a factor promoting their linkage through pottery decoration. It may be significant that mandibles--the bones utilized for this purpose--are absent among the faunal remains, except for a few small fragments. Presumably, they were being curated for this special use, rather than discarded along with other bones. Because of these probable associations--with coastal environments, hunting collectives and the summer season--pottery decoration with the porpoise tooth stamp could have been heavily laden with meaning for the coastal porpoise-hunting groups, potentially conveying a self-identity founded upon the pattern of subsistence activities in these coastal areas. No other examples of pottery decoration with marine mammal bone or tooth impressions are known to the authors outside of the Baltic region. However, the widespread practice of impressing pottery with the serrated edges of Cerastoderma shells in the Neolithic period in south-western Europe ("Cardial pottery") and the use of the tips of marine snail shells for pottery decoration in Norway (p. 111) might likewise be seen as reflecting the prominence of coastal resources in the world-view of the communities inhabiting these areas. However, how may we interpret the examples of pottery stamped with the teeth of this marine mammal that occur on inland sites? As discussed by Berzins and Dumpe , there are several possible explanations. The first possibility to consider is seasonal movement by groups from the inland lake basins to the coast for the purpose of exploiting seasonal resources (porpoise in the summer, but potentially also other resources at different times of the year), whereby pottery made at the coast during this season was being taken to inland sites along with other equipment and maybe used for transporting foodstuffs. However, the evidence from inland faunal assemblages and stable isotope data forces us to reject this hypothesis. The identified faunal remains from Neolithic sites in the Lubans area do not include any marine species, which is unsurprising, considering the long distance from the seacoast. There is evidence of marine resources from sites in the Lake Burtnieks basin, located much closer to the sea. Thus, the faunal assemblage from Rinnukalns, in addition to mass remains of freshwater and migratory fish, also includes a minor proportion of marine fish , and seal teeth are represented among the tooth pendants from Neolithic graves at Zvejnieki (pp. 144-147). However, the contact between this lake basin and coastal areas did not involve large-scale provision of marine food resources. This is demonstrated by the stable isotope data for human skeletal remains from the middle and second half of the 4th millennium BC at Rinnukalns and Zvejnieki, which indicate a diet based largely on freshwater fish, with no evidence for significant marine protein input in this period . If we reject seasonal coast-inland mobility as an explanation for the occurrence of porpoise tooth decoration on pottery from inland sites, then we must address the possibility that the pottery vessels were among the items being transferred within the regional exchange network of this period. The exchange of tools used for making the porpoise tooth decoration, although it cannot be ruled out, seems markedly less plausible, since it would not account for the occurrence on inland sites of other characteristic traits of pottery from the coastal sites, as described above. The idea that pottery was being exchanged in the Neolithic does run contrary to the traditional view that early prehistoric pottery was locally made and, thus, serves to characterize the material culture of that particular group. On the other hand, the Neolithic archaeological assemblages from the eastern Baltic and neighboring regions testify to the existence of a highly developed system of exchange, in the frame of which amber ornaments, flint and chopping tools of Karelian metatuff were distributed across a very wide area . Presumably, this exchange system also included a range of organic objects (e.g., skins of marine and land animals, honey and wax, plant materials) that have not been preserved. In this context, the idea that pottery could also have constituted an item of exchange seems entirely plausible, even if the focus may have been on other exchange items, the pottery vessels serving merely as containers for transportation. A third hypothesis to consider is that practices of exogamy contributed significantly to this pattern. If pottery-makers came to live with their spouses in inland lake basin communities, then they may have brought their own tools with them and may have applied their pottery production skills in the new place of residence. The latter two hypotheses are not mutually exclusive: both artefact exchange and exogamy could have functioned concomitantly in the maintenance of links between coastal and inland communities, and so we could potentially be dealing with the movement of potters (along with their decorating tools) as well as the movement of pottery vessels. Future petrographic and chemical analysis to characterize the clays and tempering materials of the region's Neolithic pottery should permit the isolation of non-locally made ceramics. In addition, we require a better understanding of the social relationships governing the long-distance movement of various materials and finished artefacts in the Neolithic period in the eastern Baltic and neighboring areas. Moreover, this should enable a clearer contextualization of the pottery stamped with porpoise teeth. 5. Conclusions The evidence from archaeological sites in the eastern Baltic region significantly enhances our understanding of the Holocene history of the harbor porpoise in the Baltic Sea basin. Seldom encountered in eastern Baltic waters in recent centuries, the porpoise was a common seasonal visitor, especially in the period ca. 3400-3000 cal. BC, when it had a major economic importance for the coastal communities of the Stone Age, as reflected by its representation in faunal assemblages. Additionally, the porpoise mandible was very commonly used as an instrument for decorating pottery, producing distinctive imprints that may have served as an expression of the value that coastal communities of that time attached to this animal. The occurrence of this kind of ornamentation also on pottery from inland sites is a very important marker of coast-inland contact, the nature of which remains to be further investigated. Acknowledgments The research on zooarchaeological finds from Estonia was conducted using the NATARC core infrastructure funded by the Estonian Research Council (TT14). Supplementary Materials The following supporting information can be downloaded at: Table S1: Data on vessels from Neolithic sites decorated with porpoise tooth impressions on the exterior. Click here for additional data file. Author Contributions Conceptualization, methodology, formal analysis, investigation, writing--original draft preparation, review and editing, L.L. and V.B. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Zooarchaeological data of Estonia will be available through the Estonian Archaeology dataset ArhIS accessed on 15 January 2023). During the improvement of the dataset, the access is available only for administrators and registered users. Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study, nor the collection and interpretation of data. Figure 2 Neolithic sites with bone finds of porpoise (marked with porpoise symbol) and/or pottery with porpoise tooth impressions. 1--Kunda Lammasmagi; 2--Riigikula; 3--Vabaduse Sq. in Tallinn; 4--Kopu; 5--Naakamae; 6--Loona; 7--Silinupe; 8--Slocene; 9--Sarnate; 10--Purciems; 11--Rinnukalns; 12--Zvejnieki; 13--Malmutas griva; 14--Sulka; 15--Piestina; 16--Sventoji. Figure 3 (a) Porpoise mandible in the collection of the Latvian Museum of Natural History used for the experiment; (b) tooth impressions obtained; (c) mode of holding the mandible for making impressions. Photos: V. Berzins. Figure 4 Pottery decorated with porpoise tooth impressions. 1--Naakamae (AI 4211: 1531); 2--Piestina (VI 90); 3, 8--Silinupe (VI 292); 4, 7--Rinnukalns (2018 excavation); 5--Malmutas griva (VI 101: 19); 6, 9--Sarnate (A 11417: 206, A 11417: 313). in the Archaeological Research Collection of Tallinn University; 2, 3, 5, 6, 8, 9--held at the National History Museum of Latvia; 4, 7--temporarily stored at the Institute of Latvian History, University of Latvia. animals-13-00909-t001_Table 1 Table 1 Bone finds of harbor porpoise (Phocoena phocoena) from archaeological sites of Estonia, Latvia and Lithuania. NISP (number of identified specimens) is presented, and where available, the MNI (minimum number of individuals) is added (values separated by "/"). Site Collection No. Skull Mandibles Atlas Vertebrae 1 Limb Bones Total Kunda Lammasmagi 1 Riigikula I HI-51 3/2 Riigikula III AI 4198/AZ 1/1 Riigikula IV AI 8304/AZ 1/1 Loona AI 4129/AZ 2 2/2 Naakamae AI 4211/AZ 4 16 431 19 470/35 Kopu XI AI 6106/AZ 5 1 6 Tallinn (Vabaduse Sq.) AI 6917/AZ 33 1 6 77 15 132/8 Tallinn (6A Tatari St.) AI 8636/AZ 1 1/1 Silinupe 29 105 2 136 Sventoji 2B 1 1 Sventoji 3B 3 3 1 Includes a few ribs. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000224 | The thermal environment is a major factor influencing amphibians. For example, amphibian reproduction occurs in specific temperatures, and minor changes in this aspect could have negative impacts on this biological process. Understanding the potential effects of temperature on reproductive output is important from both an ecological and captive breeding colony point of view. I examined temperature effects on reproduction in axolotl reared from egg to adult at 4 temperatures (15 degC, 19 degC, 23 degC, and 27 degC) These adult axolotls (n = 174) were measured and weighed, dissected, and their gonads were removed and weighed to obtain an individual's reproductive allocation. Female axolotls reared at 23 degC had a greater Gonadosomatic Index (GSI) compared to axolotl reared at each of the other temperatures with axolotls reared at 27 degC having the lowest reproductive output. Moreover, all GSI pair-wise comparisons in the four temperature treatments were significantly different from each other (ANOVA, F (3, 66) = 61.681, p < 0.0001). Additionally male rearing temperature significantly influenced GSI (ANOVA, F (3, 89) = 10.441, p < 0.0001). Male axolotls reared at 19 degC had significantly greater GSI compared to males reared at the three other temperatures. There were no statistical differences among each of the other pair-wise comparisons. As seen in this experiment, axolotls may be especially sensitive to climate-driven warming due to their highly permeable skin and paedomorphic life history. Understanding how axolotls and other amphibian species adjust to the challenges of climate change is important in the management of this imperiled taxa. Gonadosomatic Index gametogenesis climate change amphibian This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. pmc1. Introduction Caudates are especially sensitive to changing temperatures due to their lack of thermal regulation. Aquatic temperatures influence growth and development during the larval period and may impact sexual development and induce sex reversal . Two literature reviews examined the influence of temperature on the developmental plasticity of amphibian larvae and determined that age and size at the onset of metamorphosis were generally lowest at the warmest temperatures. Amphibian larvae that develop faster and metamorphose at a smaller body potentially impact fitness-related traits . Further, larval amphibians may be more vulnerable than adults to temperature variations and are likely to encounter higher variation in temperature living in the aquatic environment. Larval amphibians often prefer specific temperatures in lab experiments and this behavior can change depending on developmental stage . Temperature preference also occurs in adult obligatory aquatic salamanders (Amphiuma tridactylum) , and acclimation temperature can influence larval and adult preferred temperature. For example, aquatic salamanders, Cryptobranchus alleganiensis (hellbenders) and Necturus maculosus (mudpuppies), selected the lower temperatures in a gradient when acclimated at 5 degC and avoided warmer temperatures . In hellbenders, water temperature can impact the pH and PCO2 , and in Ambystoma texanum (small-mouth salamanders), water temperature can influence physiological immune function , and metabolic rates , Rearing temperature can reduce growth and survival of Andrias davidianus (the Chinese giant salamander) and play an important role in the initiation of reproductive cycles , with low temperatures inducing early timing of female gamete maturation, as shown in Siberian salamanders (Salamandrella keyserlingii) captured during breeding migrations . Thus, seasonal temperatures may affect spermatogenesis and ovulation in temperate salamander species and their endocrine e and exocrine control and constraints . Notwithstanding these studies, little is known whether and how water temperature affects gonads growth in urodeles. This information is of importance for the development of temperature regimes for rearing amphibians in captive colonies (including germplasm repository development), and in understanding the effects of climate induced changes on life histories traits including reproduction. The present study examines the effect of water temperature on the Gonadosomatic Index (GSI) in the Axolotl, Ambystoma mexicanum. These salamanders are imperiled and near extinction in nature because of invasive predatory fish, pollution, and urbanization . Axolotls are thriving in domestication--as exotic pets, or in laboratory colonies where they are used as model organisms for biological research. This species has been cultured in the lab as surrogates for wild Ambystoma species on the research of cold storage and cryopreservation of spermatophores and for examining temperature influence on reproductive physiology . Axolotls possess features typical of salamander larvae, including external gills, and are paedomorphic (i.e., retaining juvenile characteristics as adults), which allows them to exploit water throughout their entire lifespan. By living in water, however, the species may be more vulnerable to changes in water temperature or quality compared to amphibians that are both land and water dwelling. Thus, it is important to know how the effects of temperature can influence reproduction of this species and other cold-blooded vertebrates. 2. Materials and Methods 2.1. Animals This study took place at the Warm Springs Fish Technology Center, U. S. Fish and Wildlife Service, in Warm Springs, Georgia. Male and female adult axolotl originally obtained from the University of Kentucky's Ambystoma Genetic Stock Center (AGSC) were paired together in 20 degC water in three containers to obtain eggs for this experiment. Approximately 75 larvae (three weeks old) from each of three clutches were mixed and divided into four groups and put in four tanks (244 cm x 61 cm x 24 cm) that were filled with artesian spring water (pH x = 6.8 +- 0.2) and recirculated through a chiller/heater which maintained temperatures at 15 degC, 19 degC, 23 degC, and 27 degC. Temperatures were checked using a YSI Pro 20i digital meter every other day and thermostat was adjusted if needed. Rearing temperatures were within the range of temperatures (10 degC to 28 degC) that axolotl have been successfully cultured . Axolotls were exposed to a 12 h light and 12 h dark photoperiod and fed brine shrimp daily until larvae were approximately 5-6 cm in total length and thereafter fed ad libitum rations of a prepared pellet diet obtained from the AGSC. This feed was broadcast haphazardly throughout the tank 5-6 days a week and larvae ate freely. Periodically, the four systems were tested for ammonia (x < 0.1), nitrite (x = 0.05), and alkalinity (x = 15 mg/L). 2.2. Gonads Collection As axolotls matured in culture tanks, individuals were sampled starting at 12 months of age (starting in March 2022)--those not sampled remained exposed to culture temperatures until collected at a later date (up to 15.5 month of age). When collected, individuals were euthanized by adding 10.0 g of Tricaine Methane-Sulfonate (MS-222) and two parts of sodium bicarbonate to 1 L of water. Salamanders were placed in the solution and 10 min after visible breathing stopped, Snout-Vent-Length (SVL, distance from the tip of the snout to the anterior angle of the vent)) (mm) was measured, then individuals were dried with a paper towel, and weighed (body mass: BM) to within 0.1 g using an electronic balance. Individuals were dissected, testis or egg masses removed, and these were weighed to 0.1 g and photographed. All axolotls were subsequently frozen individually. 2.3. Statistical Analysis Gonadosomatic index (GSI) was obtained by the dividing testis or eggs mass versus the body mass (in grams). GSI is widely used in studies of reproductive cycles of different groups of animals . These data were arcsine square root transformed to minimize the heterogeneity of variances among treatments . Body size data were log-transformed before analysis. An ANOVA was performed on these data using the Excel2016.lnk software package (Microsoft, Redmond Washington, DC, USA) to analyze the effect of rearing temperature on the GSI (p = 0.05 level of significance). If the p-value from the ANOVA was less than the significance level, a Tukey-Kramer post hoc test was done to examine which groups are different from each other. 3. Results 3.1. Females Female body size was significantly affected by rearing temperature. Axolotls reared at 15 degC and 23 degC and had a greater SVL and body mass compared to axolotls reared at 19 degC and 27 degC temperatures (Table 1). These body size differences were statistically different. SVL: ((ANOVA, F (3, 65) = 13.625, p < 0.0001), Body mass: (ANOVA, F (3, 65) = 31.907, p < 0.0001). Additionally, female axolotls reared at 23 degC had a greater GSI compared to axolotl reared at each of the other temperatures . All pair-wise comparisons in GSI in the four temperature treatments were significantly different from each other (ANOVA, F (3, 66) = 61.681, p < 0.0001, Figure 1), with axolotls reared at 27 C having the lowest reproductive output. 3.2. Males Male body size was significantly affected by rearing temperature. Axolotls reared at 23 degC had a greater SVL (115.4 mm) and body mass (93.4 g) compared to axolotls reared at other temperatures (Table 1). These body size differences were statistically different. SVL: ((ANOVA, F (3, 86) = 4.572, p = 0.0052), Body mass: (ANOVA, F (3, 86) = 14.143, p < 0.0001). Rearing temperature significantly influenced GSI (ANOVA, F (3, 89) = 10.441, p < 0.0001). Male axolotls reared at 19 degC had significantly greater GSI compared to males reared at the three other temperatures . Males in the warmest water temperature (27 degC) had the smallest GSI compared to axolotls reared at 15 degC and 23 degC temperatures, but these differences were not statistically different. 4. Discussion 4.1. Females Body size of females and the growth development of gonads depended strongly on temperature regime. Axolotls were larger both in length and weight when reared at 15 and 23 degC. Interestingly, gonads size of axolotls reared at the coldest temperature (15 degC) did not increase in proportion to body mass. These salamanders may have the capacity to allocate food energy to growth rather than to reproduction as temperature conditions at 15 degC may not be ideal. Alternatively, if temperature environments are optimal, females will growth larger and produce more eggs. This likely occurred in females reared at 23 degC as axolotls were larger and the GSI was significantly greater compared to females at the three other temperatures. 4.2. Males Similar to females, male body size was greatest at 15 degC and 23 degC, however males reared at 19 degC had a significantly greater GSI compared to males reared at the three other temperatures. Again, the potential for an energy trade-off between growth and reproduction is likely for males reared at different temperatures. 4.3. Effects of High Rearing Temperature and Climate Warming Both females and males were smaller in body size and produced relatively a smaller percentage of gonads when reared at 27 degC. This was particularly true for females. High temperatures may influence not only gonads production but may also affect gamete maturation or increase gamete mortality as seen in fish and mammals . Seasonal temperature variation can influence spermatogenesis and ovulation is some salamander species . I4 nature, axolotl growth and reproduction could be affected by increased water temperatures that arise from climate change. This species originated in cold water (<16 degC) lakes in Mexico and ideal water temperatures for rearing axolotls in the lab is 16-18 degC. Water temperatures above 24 degC can put stress on the animals and result in a loss of appetite (personal observation) and may make axolotls more vulnerable to parasites. A previous study suggested that maintaining axolotl at 24 degC or below can accelerate growth without serious detrimental effects but rearing temperatures above that would reduce axolotl developmental rates. This occurred in the present experiment as rearing temperatures of 27 degC resulted in axolotl reduced body size and decreased the relative mass of testis and the number of eggs. It is possible that the 27 degC water temperature affected hormonal function in these salamanders and suppressed gametogenesis. Future studies are needed to address the role of temperature on hormones, gamete quality, and paternal investment in offspring. 5. Conclusions These results suggest that the reintroduction and translocation of axolotls into former and new habitats should identify water temperature as an important component in conservation efforts. Previous research that examined axolotl distribution found this species in water temperatures ranging between 16 to 23 degC . As seen in this experiment, males and females should be reared at different temperatures to optimize reproductive output and may be especially sensitive to high temperatures. Whether temperature influences other maternal contribution to offspring, i.e., input into other fitness-related qualities (e.g., egg or hatching size) is presently unknown. While this study examined the effects of constant temperatures on axolotl reproduction, additional research should focus on the consequences of variable thermal environments. The ability of species to adapt to this extrinsic factor behaviorally or physiologically is little known. Understanding how axolotls and other amphibian species adjust to the challenges of temperature variation is important in the management of this imperiled taxa. Acknowledgments I thank William Wayman for the construction of systems for rearing axolotls and thank William Wayman, Jackie Zelco, and Isabel Veith for their help in feeding animals. I especially thank Sam Figiel and Aria Foster for assistance in dissecting axolotls and Yue Liu for reviewing an earlier version of the manuscript. I gratefully acknowledge the AGSC which received financial support (P40-OD019794) from the Office of Research Infrastructure Programs at the National Institutes of Health. Institutional Review Board Statement All procedures involving animals were reviewed and approved by the Animal Care and Use Committee of the U.S. Fish and Wildlife Service Warm Springs Fish Technology Center. All the animals used in this study were cared for in accordance with the Institutional Animal Care and Use Committee guidelines at the Warm Springs Regional Fisheries Center that conformed to standards established by the United States Office of Lab Animal Welfare and the United States Department of Agriculture. Approval code: WSFC 2021-05. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available upon request from the corresponding author. Additionally, data files have been uploaded to FigShare on Gonadosomatic Index (GSI) of female axolotls, Ambystoma mexicanum. Different letters indicate statistically significant differences among temperatures. Mean +- standard deviation. Figure 2 Effects of rearing temperature (15 degC, 19 degC, 23 degC, and 27 degC) on Gonadosomatic Index (GSI) of male axolotls, Ambystoma mexicanum. Different letters indicate statistically significant differences among temperatures. Mean +- standard deviation. animals-13-00874-t001_Table 1 Table 1 Effects of rearing temperature (15 degC, 19 degC, 23 degC, and 27 degC) on snout-vent-length (SVL) (mm) and body mass (g) of female and male axolotls, Ambystoma mexicanum. Different letters indicate statistically significant differences among temperatures. Mean +- standard deviation. Females 15 degC 19 degC 23 degC 27 degC n 25 21 16 21 SVL 110.6 +- 12.6 a 103.8 +- 5.4 b 114.4 +- 5.4 a 101.6 +- 8.9 b Body Mass 95.9 +- 12.6 a 70.6 +- 7.9 b 93.1 +- 12.7 a 57.0 +- 18.3 b Males 15 degC 19 degC 23 degC 27 degC n 27 30 20 12 SVL 111.1 +- 4.1 a 109.5 +- 5.6 a 115.0 +- 6.1 b 109.2 +- 8.6 a Body Mass 86.5 +- 7.8 a 72.3 +- 12.3 a 92.1 +- 17.8 b 72.1 +- 13.1 a Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000225 | Autophagy is a fundamental cellular process implicated in the health of the cell, acting as a cytoplasmatic quality control machinery by self-eating unfunctional organelles and protein aggregates. In mammals, autophagy can participate in the clearance of intracellular pathogens from the cell, and the activity of the toll-like receptors mediates its activation. However, in fish, the modulation of autophagy by these receptors in the muscle is unknown. This study describes and characterizes autophagic modulation during the immune response of fish muscle cells after a challenge with intracellular pathogen Piscirickettsia salmonis. For this, primary cultures of muscle cells were challenged with P. salmonis, and the expressions of immune markers il-1b, tnfa, il-8, hepcidin, tlr3, tlr9, mhc-I and mhc-II were analyzed through RT-qPCR. The expressions of several genes involved in autophagy (becn1, atg9, atg5, atg12, lc3, gabarap and atg4) were also evaluated with RT-qPCR to understand the autophagic modulation during an immune response. In addition, LC3-II protein content was measured via Western blot. The challenge of trout muscle cells with P. salmonis triggered a concomitant immune response to the activation of the autophagic process, suggesting a close relationship between these two processes. autophagy skeletal muscle fish immune response Piscirickettsia salmonis Fondo Nacional de Desarrollo Cientifico y Tecnologico FONDECYT3200172 1191763 This research was funded by Fondo Nacional de Desarrollo Cientifico y Tecnologico FONDECYT, postdoctoral grant number 3200172, and FONDECYT, regular grant number 1191763. pmc1. Introduction Autophagy is a highly conserved catabolic process essential for cellular homeostasis, degrading cytosolic macromolecules and damaged organelles to guarantee energy supply and nutrient availability for the cell. Furthermore, autophagy can modulate innate and adaptative immunity, contributing to the clearance of pathogens from the cell . Under normal conditions, autophagy occurs at low levels in almost all cells, but is strongly induced under nutrient deprivation, amino acid starvation, cellular stress, cytokine exposure and pathogen infections . Additionally, autophagy can act through a noncanonical pathway in antigen processing and presentation for MHC-I and MHC-II, restricting intracellular pathogens and regulating adaptive immunity . At the molecular level, the autophagic pathway involves the concerted action of evolutionarily conserved ATG gene products involved in the initiation (atg9, atg13 and becn1), autophagosome formation (atg5, atg12 and atg16), the elongation of autophagic processes (atg7 and atg4), and autophagosome closure (gabarap and lc3) . Autophagy is triggered by activating a regulatory protein complex that recruits microtubule-associated light chain protein 3 (LC3) to the nascent autophagosome . The conversion of LC3 into its active form, LC3-II, through conjugation to phosphatidylethanolamine (PE), allows for the transformation of the membrane into a closed double-membrane system . Lastly, the autophagosome binds to the endosomal or lysosomal compartment, forming the autolysosome where organelles and macromolecules are degraded by a pool of proteolytic enzymes . In mammals, autophagic activation is associated with immune signals and molecular pathways, involving toll-like receptor (TLR) activation through different pathogen-associated molecular patterns (PAMPs) . For instance, autophagy activated by the endosomal TLR signaling pathway in macrophages plays a key role as a mechanism for Leishmania major infection resistance . Mammalian skeletal muscle, a nonclassical immune tissue, possesses several membrane-bound TLRs with the ability to detect different PAMPs, triggering signaling pathways to activate autophagy . These findings associate TLR signaling and autophagy, providing a potential molecular mechanism for the induction of autophagy in response to pathogen invasion. Therefore, the ability of TLR ligands to stimulate autophagy may be used to treat intracellular pathogens in mammals . Moreover, several proinflammatory cytokines, such as IFN-g, TNF-a, IL-1, IL-2, IL-6, and TGF-b induce autophagy, while anti-inflammatory cytokines such as IL-4, IL-10, and IL-13 display an inhibitory effect . All these data suggest a close relation between the immune response and autophagy in mammalian skeletal muscle. However, this interaction is unknown in fish, and only a few reports related to autophagy exist. Nevertheless, due to the direct relation of autophagy and growth, a key parameter for fish-industry productivity, autophagic markers have been studied under different diets and nutritional trials. Results showed a direct association between fish's energy requirement and the activation of autophagy . For instance, the autophagic flux and the overexpression of autophagic genes atg4, atg9, atg12, lc3, gabarap and becn1 was observed in vitro in epithelial gill cell line RT-gill-W1 of rainbow trout under nutrient restriction, and in the muscle of trout challenged with Flavobacterium psychrophilum . Nevertheless, the modulation of autophagy in fish muscle cells during an immune-like response against an intracellular pathogen has not been elucidated. This study aims to describe and characterize autophagic modulation through the immune response of fish muscle cells after a challenge with a critical bacterial pathogen for the salmon industry. Through the immune challenge of primary cultures of muscle cells with Piscirickettsia salmonis, a fastidious intracellular pathogen, we revealed the transcript upregulation and protein production of several immune markers and genes involved in autophagy. Results obtained in the present work give new insight into the role of autophagy in the immune response against bacterial pathogens in muscle cells. 2. Materials and Methods 2.1. Ethics Statement The present research was approved by the bioethics committee of Pontificia Universidad Catolica de Valparaiso (PUCV) BIOEPUCV-B 334-2020 and the Agencia Nacional de Investigacion y Desarrollo (ANID) of the Chilean government, and adhered to all animal welfare procedures. 2.2. Fish Husbandry In total, 24 rainbow trout (Oncorhynchus mykiss) with body weight of 10 +- 1.7 g and body length of 10 +- 1.5 cm were obtained from the Rio Blanco Aquaculture Center (Valparaiso, Chile). These fish were kept in 3 tanks at a density of 8 fish per 25-L tank, using 1 tank per trial. Fish were maintained at a temperature of 16 degC, fed daily with commercial feed, and provided with a photoperiod of 13 h of light and 11 h of darkness. 2.3. Primary Culture of Muscle Cells Muscular cells were prepared from 6-8 g of the skeletal muscle of four rainbow trout as previously reported . Briefly, the dorsal white muscle was collected and disintegrated in Dulbecco's Modified Eagle's Medium (DMEM) containing 9 mM NaHCO3, 20 mM HEPES, 10% horse serum at pH 7.4, 100 U/mL penicillin, and 100 mg/mL streptomycin (Sigma, St. Luis, MO, USA). After mechanical dissociation, the muscle was washed with DMEM and then digested with 0.2% collagenase solution in DMEM for 1 h at 18 degC. The suspension was centrifuged at 500 g for 5 min at 15 degC, and the resulting pellet was digested with a 0.1% trypsin solution in DMEM for 30 min at 18 degC. Trypsin was deactivated with complete medium (DMEM containing 10% fetal bovine serum, 100 U/mL penicillin, and 100 mg/mL streptomycin at pH 7.4), the suspension was filtered and centrifuged at 5000x g for 10 min at 18 degC, and 5 mL of DMEM was lastly added to the resulting pellet. The cell suspension was collected to count cells and evaluate viability with Trypan Blue 0.2%. Cells were seeded at a density of 5 x 105 per well in plates previously treated with poly-L-lysine (2 mg/cm2) and laminin (20 mg/mL). The cells were incubated at 18 degC for 14 days, 7 days in a proliferation medium containing DMEM, 9 mM NaHCO3, 20 mM HEPES, 10% fetal bovine serum, 100 U/mL penicillin, and 100 mg/mL streptomycin at pH 7.4, and 7 days in a differentiation medium composed of DMEM (9 mM NaHCO3, 20 mM HEPES, 100 U/mL penicillin, and 10 mg/mL streptomycin). This procedure was repeated three times (n = 3) per experimental trial described in the next sections. 2.4. Piscirickettsia salmonis Culture and Infection Protocol A P. salmonis field isolate, Psal-104a, was obtained from the Chilean National Piscirickettsia salmonis Strain Collection at Pontificia Universidad Catolica de Valparaiso (PUCV). The bacteria were cultured in basal medium (BM) broth composed of yeast extract (Merck, St. Louis, USA) 2.0 g L-1, peptone from meat (peptic digested, Merck) 2.0 g L-1, (NH4)2SO4 1.32 g L-1, MgSO4*7H2O 0.1 g L-1, K2HPO4 6.3 g L-1, NaCl 9.0 g L-1, CaCl2*2H2O 0.08 g L-1, FeSO4*7H2O 0.02 g L-1, and glucose 5 g L-1 at 18 degC at 100 rpm. Exponentially growing P. salmonis (O.D. 600 = 0.3) was recovered via centrifugation at 5000x g, washed three times with saline-buffered solution (SBS: 0.15 M NaCl, 7.3 mM KH2PO4, 11.5 mM K2HPO4, pH 6.0) supplemented with 4% lactose, and resuspended in DMEM containing 9 mM NaHCO3, 20 mM HEPES, at pH 7.4. Bacterial cells were counted using a Petroff-Hausser chamber. Muscular cells were infected at a multiplicity of infection (MOI) of 10 for 4, 6, 8, and, 24 h. After the experimental times, the pathogen was removed and then sampled. As a positive control for autophagic activation, muscle cells were treated with rapamycin (50 nm), and DMEM was used as a vehicle for control, sampled at the beginning of the experiment (0 hpi). 2.5. Quantitative Real Time PCR (qPCR) The total RNA from the primary culture of skeletal muscle was extracted according to the manufacturer's guidelines for E.Z.N.A total RNA Kit I (Omega Bio-tek, Norcross, GA, USA), and quantified with NanoDrop LITE spectrophotometer (Thermo Scientific, Rockford, IL, USA). Residual genomic DNA was removed, and 1 mg of RNA was used for cDNA synthesis via RevertAid First strain cDNA Synthesis Kit (Thermo Scientific, Rockford, IL, USA) according to the manufacturer's protocol. Real-time quantitative PCR (qPCR) assays were performed in a AriaMx Real-Time PCR System (Agilent Technologies, Santa Clara, CA, USA) with 15 mL volume reactions, of which 1 mL was cDNA (a 2-fold dilution), 0.2 ml of each primer (250 nM), and 8.8 mL of Takyon master mix (Eurogentec, Seraing, Belgium). The primers used in this study were designed and validated in our laboratory, and the sequence and efficiency of each primer are listed in Supplementary Table S1. Thermal cycling conditions were as follows: initial activation 95 degC for 10 min, 40 cycles of 30 s denaturation at 95 degC, 30 s annealing at 60 degC, and 30 s elongation at 72 degC, and each sample was loaded in duplicate. Relative expression analysis was conducted using geNorm software (accessed on 30 March 2021)), and the results are expressed as fold changes using EF-1a and b-actin as housekeeping reference genes. 2.6. Western Blot Total protein was extracted from primary culture cells in 150 mL Piercetm RIPA buffer (Thermo) supplemented with 8 mM EDTA, PMSF 1 mM, and a protease inhibitor cocktail (Calbiochem, San Diego, CA, USA), centrifuged at 12,000x g, and solubilized at 4 degC. Protein concentration was determined using a Pierce BCA Protein Assay Kit (Thermo Scientific, Hanover Park, IL, USA). The total protein (10 mg) was loaded into each line, separated with 18% SDS-PAGE, transferred to a nitrocellulose membrane, and blocked for 1 h at 37 degC in Tris-buffered saline (TBS-Tween) with 3% BSA. Primary antibody incubations (LC3A/B (D3U4C) XP(r) Rabbit mAb #12741, Actine (INVITROGEN), and ant-Rab7a, diluted 1:1000, 1:2000 and 1:500, respectively) were performed overnight at 4 degC. The anti-Rab7a polyclonal antibody was developed in our lab. Briefly, a recombinant Rab7a was used for specific antibody production . CF-1 mice (5 weeks old) were subcutaneously injected at 1, 14, and 28 days with 30 mg of peptide diluted 1:1 in FIS, as a T helper cell activator, and in 1:1 Freund's adjuvant (Thermo Scientific). The antiserum was collected on Day 42 and centrifuged at 700 g for 10 min, and the supernatant was stored at -20 degC. Antibody validation was determined via Western blot . Membranes were washed with 1X TBS and incubated for 1 h at room temperature with the appropriate secondary antibody. After washing, the membranes were visualized using commercial kit WESTAR SUPERNOVA from Cyanagen. Then, the membrane was visualized with the ChemiDoc Imaging Systems Bio-Rad system (Bio-Rad Laboratories, Hercules, CA, USA). Digitized images were used for the densitometric analyses of the bands in Image J software(National Institutes of Health, Bethesda, Maryland, USA). Differences are expressed as fold changes in protein content. Western blots were performed for all individual samples per experimental treatment; however, only one representative blot film is shown in the figures . 2.7. Immunofluorescence Adherent cells were washed with 1X PBS and fixed with 4% paraformaldehyde (PFA) (in 1x PBS) for 10 min and permeabilized/blocked with 3% BSA with 0.3% Triton in 1X TBS for 30 min, and the quenching solution (50 mM ammonium chloride) was added for 10 min. Then, the cells were incubated overnight with the anti-LC3 antibody diluted at 1:100 (LC3A/B (D3U4C) XP(r) Rabbit mAb #12741 in 1% BSA at room temperature. Samples were washed with 1X PBS and 0.02% TBST, and incubated with a commercial secondary antibody (1:750) (Invitrogen, Thermo Scientific) for 90 min at room temperature. Nuclear staining was performed with DAPI (Vector Laboratories) for conventional fluorescence microscopy, following the manufacturer's instructions. For image capture, the samples were placed in a Leica CTR5000fluorescence microscope (Leica Microsystems, Wetzlar, Germany). Western blots were analyzed using the LC3-II/actin and Rab7a/actin ratios. 2.8. Statistical Analysis All generated data were evaluated with one-way ANOVA and Student's t test. Data are expressed as the mean (n = 3 per treatment) +- standard error of the mean (SEM), and p < 0.05 was considered statistically significant. All analyses were performed using general linear models on Graph Prism 7.0 software (GraphPad Company, Boston, MA., USA). 3. Results 3.1. Immune-like Response of Skeletal Muscle Cells after P. salmonis Challenge To understand and characterize the response of muscle cells against bacterial pathogens, rainbow-trout skeletal muscle cells were challenged with P. salmonis for 6, 8, and 24 h. Next, immune molecular markers tlr3, tlr9, il-1b, tnfa, il-8, hepcidin, mhc-I and mhc-II were measured with RT-qPCR, and results showed a concomitant overexpression of toll-like receptors 3 and 9 after 6 h of challenge . Proinflammatory cytokines il-1b, tnfa and il-8 were modulated compared to the noninduced controls, where tnfa and il-8 were upregulated significantly after 6 and 8 h after the challenge, respectively . Antimicrobial peptide hepcidin increased after 6, 8, and 24 h after the challenge, but no statistical significance was observed . No changes were observed in the mRNA levels of mhc-I and mhc-II during the entire trial . 3.2. Autophagic Modulation in Muscle Cells after P. salmonis Challenge To describe the modulation of autophagy in muscle cells after bacterial challenge, autophagic markers were analyzed via RT-qPCR, Western blot, and immunofluorescence. Rapamycin was used as the positive control of autophagic activation. Autophagic genes associated with the induction of this process were upregulated, particularly becn1, of which the mRNA level was significantly increased after 6 and 24 h of the challenge . In the case of autophagosome formation genes, the overexpression of atg5 was observed after 6 h of treatment, while the transcript level of atg12 was downregulated after 8 h . The mRNA levels of atg4, an elongation of an autophagosome molecular marker, was downregulated after 8 h of challenge . Lastly, the transcript level of lc3 was significantly downregulated after 8 h of challenge . At the protein level, protein autophagic marker LC3-I/LC3-II was evaluated via immunofluorescence and Western blot. Agreeing with the gene expression of autophagic induction gene analysis, the protein content of LC3 showed an increase in fluorescence signal in the muscular cells challenged with P. salmonis compared with the control group at 6 h after challenge . An increase in the LC3-II protein content was observed through Western blot analysis after 6 h of stimuli . In addition, the mRNA levels of small GTPase proteins rab5a and rab7a were upregulated at 6 h after challenge, while the transcript level of rab11a was increased after 24 h . Lastly, the protein content of Rab7 showed an increasing trend through Western blot . 4. Discussion In mammals, the ability of muscles to respond and participate in the immune response against pathogens and in autoimmune events is well-characterized . This ability is represented by the immunocompetent attributes of muscle cells, such as the expression of costimulatory molecules, antigen-presenting machinery, proinflammatory cytokines, and pathogen recognition receptors . Moreover, the interaction between muscle cells and resident immune cells is an essential step for wound healing and damage regeneration in this tissue . In fish, the skeletal muscle appears as an active immunological organ, where immune reactions occur after an in vivo challenge with bacterial pathogens . However, the ability of a muscle cell to express classical immune-like molecules by itself is still under study, and only few reports address how this type of cells may respond against PAMPs and pathogens . For example, rainbow-trout myotubes responded against Piscirickettsia salmonis through the upregulation of tlr1, tlr22, and il-8 at 8 h after a challenge . In the present study, the immune response against P. salmonis generated a concomitant overexpression of tnfa, tlr3, and tlr9 after 6 h of challenge. Toll-like receptors 3 and 9 are associated with an intracellular/antiviral response where these receptors can detect double-strand RNA and CpG DNA, respectively . Reports in mammals showed how these receptors can be involved in diminishing the growth of intracellular bacterium Salmonella typhimurium . Salmon head kidney cells (SHK-1) respond to an infection with P. salmonis through the overexpression of tlr1 and tlr5s . Furthermore, P. salmonis could induce a flagellin-dependent TLR5 activation in Atlantic salmon, which resulted in the upregulation of proinflammatory genes . The overexpression of intracellular receptors suggests that intracellular defense mechanisms could be activated in response to P. salmonis infections. Despite the overexpression of markers associated with an intracellular response, the RNA levels of molecular markers DotA and DotB of P. salmonis were not detected via RT-qPCR (data not shown), which could indicate that, even though the bacterium does not enter the cell, the intracellular defense mechanisms are stimulated. On the other hand, proinflammatory cytokine tnfa represents an early response of muscular cells against bacterial pathogens. Indeed, an increase in NF-kB and TNFa at 48 h after a challenge against Vibrio anguillarum was observed on fish muscle . Additionally, at 8 h after a challenge, the mRNA level of il-8 was upregulated. In higher vertebrates, TNFa induces the expression of IL-8 . This kind of response may be associated with the need for muscle cells to recruit immune cells to the site of infection, since IL-8 is a chemoattractant for leukocytes . These results contribute to existing data confirming that the muscle cell responds to a bacterial challenge by itself. However, communication with the immune resident's cells is needed to deploy an effective and robust response. In mammals, the participation of autophagy in the immune response is well-characterized, where autophagy-related gene (ATG) proteins mediate direct pathogen degradation, inflammation restriction, antigen presentation on MHC molecules and survival of memory lymphocyte populations . This process has mainly been studied for its role in the internal quality control of the cell, and for its implication in metabolism and cancer. However, autophagy can participate through a noncanonical pathway to respond against other dangerous stimuli, such as pathogen infection . In fish, the modulation of this process in a pathological context is unclear, and only a few reports show how autophagy is modulated by nutrient restriction and pharmacological treatments . Transgenic zebrafish and zebrafish cell lines were used as research tools on the autophagic regulation process, highlighting its role on the protection against pathogen infection, development, and lipid degradation . Autophagy was also linked to development and extracellular matrix formation in zebrafish . Recently, the modulation of autophagic genes atg4, becn1, atg7, lc3, atg12, and gabarap has been evaluated in rainbow-trout liver and muscle under different functional treatments, fasting, and a posteriori F. psychrophilum infection, suggesting a possible role of this process in the resistance against pathogens . In the present work, autophagic genes were downregulated in a time-dependent and coordinated way. The upregulation of becn1 was observed at 6 h after challenge; becn1 is a protein that facilitates the de novo formation of the phagophore, and is critical for the autophagic initiation in embryogenesis and antiviral responses in fish . The next step in autophagy is autophagosome formation, where molecules atg5 and atg12 are directly involved . We observed the upregulation of atg5 at 6 h after a challenge with the subsequent downregulation of atg12 after 8 h. Both genes are associated with intracellular immune response against viruses in fish, where atg5 plays crucial roles in viral replication via promoting autophagy in orange-spotted grouper , while atg12 can induce both autophagy and the Type I IFN response in large yellow croaker . These two molecules are regulated by RAB5, a small GTPase, which facilitates the early formation of the autophagosome . Six hours after a challenge with P. salmonis, the mRNA levels of rab5a and rab7 increased significantly, suggesting the activation of vesicle traffic in response to the bacteria. In mammals, Rab7a is associated with the endocytic pathway ; in fish, this molecule is related with an antiviral response , suggesting the activation of different intracellular mechanisms in response to P. salmonis. Lastly, the genes involved in the elongation and closure of the autophagosome were downregulated after 8 h after challenge, particularly atg4 and lc3. Altogether, the present data suggest a tight relation between autophagy and intracellular innate immune response, and are consistent with the used intracellular bacterial pathogen and the evaluated immune markers in our study. A crosstalk between the immune response and autophagy has been reported in mammals. For example, TLRs were directly involved with autophagic activation after TLR ligand stimulations with poly I:C and LPS, among other PAMPs . In addition, the stimulation of TLR7 with different ligands activated autophagy, eliminating intracellular microorganisms even when the target pathogen had not been canonically associated with TLR7 signaling . In this context, the recognized ability of TLR ligands to stimulate autophagy was proposed as a prophylactic alternative to treat intracellular pathogens . In the present study, tlr3, tlr9, tnfa and autophagic genes becn1 and atg5 were upregulated at the same experimental time (6 h after challenge), suggesting a relation between the autophagy and immune response of muscle cells against P. salmonis. This relation was confirmed in mammals where TNFa and other cytokines could induce autophagy . Lastly, to corroborate the activation of autophagy in rainbow-trout muscle cells, we assessed the protein level of LC3-II, a classical protein marker for autophagy. Finding higher protein content of LC3-II in the treated cells added to the presented overall results and the background information, suggesting that the muscle cell deploys an immunelike response where autophagy may play an important role for the clearance of the pathogen. Deeper functional analysis and characterization are required to corroborate the dialogue and regulation between the two essential cellular functions. 5. Conclusions The skeletal muscle of fish is a fundamental energy source for the organism and a recurrent site of infection where immunelike responses against different bacterial pathogens occur. The present study described for the first time the modulation of the immune response and its possible connection with autophagy in rainbow-trout muscle cells. The challenge of trout muscle cells with P. salmonis, an intracellular pathogen, triggered an immune response concomitant to the activation of the autophagic process. Results suggest an early response by the muscle cells against the bacteria just after only 6 h of challenge, where both immune and autophagic markers were upregulated. Considering the obtained data and the available research information, two important questions arise regarding the possible implication of P. salmonis challenge in fish muscle: (1) is autophagy acting as an intracellular immune mechanism to fight this pathogen or is the bacterium using this mechanism to enter the cell and evade the immune response? These questions are relevant and represent a new line of research that must be answered. Due to the necessity of seeking and discovering new alternatives and strategies to fight intracellular pathogens in the salmon industry, a better understanding of how autophagy participates in immune system responses may lead to the development of new technologies that allow for the effective control of intracellular pathogens, improving animal welfare and contributing to the sustainability of the global fish industry. Acknowledgments The authors would like to thank German Olivares from the Piscicultura de Rio Blanco, Los Andes, Chile for providing the fish for the experiments. Supplementary Materials The following supporting information can be downloaded at: Figure S1: characterization of Rab7a from O. mykiss.; Table S1: primers used for qPCR. Supplementary Figure S2. Original Western blot of LC3-II in skeletal muscle cells after 6 h of challenge with P. salmonis. Supplementary Figure S3. Original Western blot of Rab7a in muscle cells after 6 h of challenge with P. salmonis. Original Western blots used for the analysis and representative blot composition . Click here for additional data file. Author Contributions Conceptualization, C.A.V.; methodology, C.A.V., C.A.A., N.O. and M.A.; formal analysis, C.A.V.; investigation, C.A.V.; resources, C.A.V. and L.M.; data curation, C.A.V.; writing--original draft preparation, C.A.V., P.S. and L.M.; writing--review and editing, C.A.V.; visualization, C.A.V.; supervision, C.A.V.; project administration, C.A.V.; funding acquisition, C.A.V. and L.M. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was approved by the bioethics committee of Pontificia Universidad Catolica de Valparaiso (PUCV) BIOEPUCV-B 334-2020. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Expression of immune molecular markers in rainbow-trout muscle cells after Piscirickettsia salmonis challenge. Primary cultures of fish skeletal muscle were challenge with P. salmonis (MOI 10) for 6, 8, and 24 h. As control group, cells were treated with a vehicle (DMEM + 10% FBS). (A) Toll-like receptors 3 and 9. (B) Proinflammatory cytokines il-1b and tnfa. (C) il-8 and the antimicrobial peptide hepcidin. (D) Major complex of histocompatibility I and II (mhc-I and mhc-II). qPCR analyses were normalized with the ef-1a and b-actin genes, and the results are presented as means +- SEMs of triplicates from three independent experiments, using fold change compared to the control values (n = 3). The difference in the transcript levels is denoted by asterisks (*) considering a p-value < 0.05 (*), p-value < 0,01 (**) and p-value < 0.001 (****) significant. Figure 2 Effect of P. salmonis challenge on the expression of autophagic genes in rainbow-trout muscle cells. Primary cultures of fish skeletal muscle were infected with P. salmonis at MOI 10 for 6, 8, and 24 h. As the control, cells without bacteria were sampled at the beginning of the trial (time 0). (A) Autophagic genes becn1 and atg9 involved in the induction of this process. (B) Autophagosome formation genes atg12 and atg5. (C) Gene atg4, involved in the elongation of the autophagosome. (D) Vesicle-completion-associated genes gabarap and lc3. The data are presented as means +- SEMs of triplicates from three independent experiments, using fold change compared to the values of the time 0 group (n = 3). qPCR analyses were normalized with the ef-1a and b-actin genes. The difference in transcript levels is denoted by asterisks (**) when the main effects were significant (p < 0.01). Figure 3 Effects of P. salmonis on the level of autophagy and Rab protein markers in muscle cells challenged. Fish skeletal muscle cells were cultured and challenge with P. salmonis at MOI 10 (resuspended in differentiation medium) for 6 h. (A) Immunofluorescence of LC3 (LC3-I and LC3-II). (B) Representative Western blot of LC3-II. (C) Rab small GTPases gene expression and, (D) Representative Western blot of Rab7a. The data are presented as the means +- SEMs of triplicates from three independent experiments, using fold change compared to the control values (untreated cells, n = 3). The measure of actin was used as load control for Western blots. qPCR analyses were normalized by the ef-1a and b-actin genes. The difference between the control group and treated groups is denoted by asterisks (*) when the main effects were significant (p < 0.05). Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000226 | The aim of this study is to evaluate a laparoscopically assisted percutaneous suture (LAPS) procedure to treat inguinal hernia (IH) while preserving testicles in rams. An ex vivo experiment with six ram cadavers and a report of three clinical cases are discussed. In cadavers, both internal inguinal rings (IIR) were partially closed by LAPS. Two LAPS methods were tested: (1) using a laparoscopic portal closure device and (2) using a suture loop inserted through needles in each IIR. After each procedure, the closure was laparoscopically evaluated and the number of was recorded. The procedure was also performed on three client-owned rams with unilateral non-strangulated IH and the occurrence of re-herniation was followed up. In cadavers, LAPS of the IIRs could be easily and satisfactorily performed with either of the two systems, requiring one to three U-sutures per IIR. No differences were observed between the two surgical procedures. In two clinical cases, the procedure was successfully performed without reoccurrence of herniation or alterations in reproductive behavior in the following 3 and 6 months. In the third case, the hernia was reduced but a retroperitoneal emphysema during laparoscopy prevented hernioplasty and the animal herniated again. In conclusion, LAPS of IIR can be used as a simple and feasible treatment to preserve testicles in rams with IH. ram hernioplasty inguinal hernia laparoscopy percutaneous suture cadaver case report This research received no external funding. pmc1. Introduction Unlike direct inguinal hernia, in which the bowel penetrates directly into the abdominal wall, indirect inguinal hernia (IIH) is characterized by the intestinal bundle protruding through the inguinal canal. This type of hernia accounts for up to 7% of congenital disorders and up to 15% of all hernias in sheep . It is caused by the large size of the internal inguinal ring (IIR) in this species . Despite these hernias usually being non-strangulated, this disorder can reduce the fertility by markedly interfering with the thermoregulatory function of the scrotum and testicles. Furthermore, depending on the herniated intestinal tract, affected animals may present serious digestive problems that can be life-threatening. Surgical treatment is required when inguinal hernias occur. In humans and horses, laparoscopic techniques have been developed to access the IIR and perform partial hernioplasty, avoiding recurrence of the hernia while preserving the testicle without altering its vascularization, thus allowing the animal to maintain reproductive capacity and, therefore, value . However, this procedure is not usually performed in rams, where the most common approach is herniorrhaphy with orchiectomy . In children, partial closure of the IIR has been described using laparoscopically assisted percutaneous suture (LAPS) techniques. This procedure allows the resolution of the hernia defect in a quick, simple manner and with low recurrence rates, avoiding the use of specific high-cost consumable materials, and, fundamentally, it can be performed without the use of complex laparoscopic techniques . Recently, a Polish multidisciplinary group of human medicine pediatricians and veterinary surgeons have also reported the use of this technique in the treatment of inguinal hernia in dogs and pigs . Sheep could also benefit from hernioplasty techniques. Although laparoscopy is not so extended in ovine species as in other species, mainly because of the high costs associated, its availability is spreading and is used for some artificial insemination techniques and intrabdominal surgeries . Therefore, developing or adapting laparoscopic techniques in sheep that are simple to perform is important to advance the standard point of care in these animals. The aim of this study was to evaluate the feasibility and efficacy of using a LAPS procedure to treat inguinal/scrotal hernias while preserving testicles in rams. We hypothesized that a modified procedure based on the LAPS technique used in children could be used to achieve partial closure of the vaginal ring in rams with IH. We first conducted a cadaveric study to assess the new technique and to overcome the initial learning curve, and subsequently evaluated the clinical performance of the procedure in three client-owed rams with naturally occurring unilateral non-strangulated IH. 2. Materials and Methods 2.1. Cadaveric Study 2.1.1. Animals Six cadavers of adult rams of Rasa Aragonesa breed without signs or history of IH or testicular abnormalities were used, making a total of n = 12 IIRs to test the LAPS technique. The number of animals was based on previous studies describing the development of laparoscopic techniques . The rams were euthanized for reasons unrelated to this study. All procedures were carried out under Project Licence PI63/22 approved by the Ethic Committee for Animal Experiments from the University of Zaragoza. The care and use of animals were performed accordingly with the Spanish Policy for Animal Protection RD53/2013, which meets the European Union Directive 2010/63 on the protection of animals used for experimental and other scientific purposes. 2.1.2. LAPS Surgical Procedure A wide caudal abdominal area and scrotum were clipped and washed. Cadavers were positioned in dorsal decubitus on a hydraulic surgical table that allowed for Trendelenburg positioning and were positioned as previously described . To create the first laparoscopic portal, a 1.5 cm skin incision was made about 5 cm cranial to the prepuce and 5 cm to the right of the midline. The abdominal wall was elevated with two Backhaus towel clamps while a reusable stainless steel 11 mm diameter and 15 cm long helical optic cannula was inserted. The trocarless cannula was introduced into the abdomen with a rigid 57 or 33 cm 0deg laparoscope inside to provide laparoscopic access control. Capnoperitoneum was created with an electronic insufflator until reaching an intra-abdominal pressure of 12-15 mm Hg. Two additional reused plastic disposable trocars and cannulas of 5 or 11 mm diameter were inserted under laparoscopic visualization. These portals were placed 10-15 cranial to each inguinal ring. Regarding needle insertion for placing sutures, an incision of 3-4 cm long was mSW in the skin directly over the inguinal ring. In this way, the knots of the percutaneous sutures remain in the subcutaneous space after the final suturing of the incision . In all cases, the intervention started on the right side. Two different suture methods were used to perform LAPS on each IIR of each cadaver. The method used on each side was randomly assigned (coin-flipping method performed by the first author). With both methods, sutures should be placed partially closing the flap of the IIR against the abdominal wall, close enough to the cord to prevent the possibility of herniation but not too close as to compress the vas deferens and testicular vessels. Laparoscopic forceps were used to push caudally the testicular cord. In the needle suture loop technique (NSLT) method, a 12 G 80 mm needle was used to pass a suture loop and a suture end to perform a U-suture. First, a suture thread (polyamide 0 USP) was passed through the needle and bent back to create the loop. Then, the needle with the suture loop was inserted through the skin incision and introduced in the abdominal cavity under laparoscopic control. Once the needle with the loop was properly placed, the loop was pushed further into the abdominal cavity and retained there with laparoscopic forceps, while the needle was removed. Subsequently, a second needle was inserted in the same way but used to introduce the distal end of a 0 USP polyamide suture through it. From inside the abdomen and using laparoscopic forceps, this suture end was passed through the initial loop . The needle was then removed and the loop was pulled from outside to create a U-suture stitch around the IIR. A video showing the main steps of the procedure is provided as supplementary material available for this article online (Video S1). In the second method, the EndoClose Trocar Site Closure Device (Medtronic, Madrid, Spain) was used. This device is designed for the closure of laparoscopic portals in human surgery. It is similar to a Veress needle. The main difference is that the retractable stylet has a notched tip which is used to capture and hold sutures. Similar to the first method, the device with the suture loop was punctured through the skin incision under laparoscopic guidance and laparoscopic forceps were used to retain the suture loop inside the abdomen while the device was withdrawn. With a second puncture of the EndoClose, the initial loop was grasped and externalized to create a U-suture in the IIR. 2.1.3. Assessment of IIR Partial Closure Proper partial closure of the IIR was confirmed by inserting a blunt laparoscopic trocar through an incision in the scrotum and tunica vaginalis. Prior to tightening the suture, the trocar should easily enter the abdomen (pre-closure control). After knotting the suture on the outside, it was checked whether it was possible to insert the trocar and the outcome was recorded (Supplementary Materials, Video S2). If necessary, an additional suture loop was performed using the same technique as for the first stitch. The number of suture stitches required was recorded. 2.2. Clinical Cases This part of the study was also approved by the Ethic Committee for Animal Experiments from the University of Zaragoza (Project Licence PI66/22) and informed owner (or an authorized agent for the owner) consent was obtained before enrolling any ram. Three cases of herniated rams referred to our surgical service and subjected to IIR hernioplasty using the LAPS approach were reported. Since owners preferred to preserve the affected testicle, this surgical option was offered. Informed owner consent was obtained after specifically communicating that this disorder could have a hereditary component in case the animals had an intended reproductive use. Follow-up was performed with owners or referrals via telephone calls between 3 to 6 months after surgeries. 3. Results 3.1. Cadaveric Study All six carcasses used were of the Rasa Aragonesa breed. The approximate age and weight of cadavers are shown in the Table 1. The surgical position allowed good visualization of the surgical area, although, in some cases, the cadaver slightly tilted with wedge-folded towels to work on each side. In the initial laparoscopic examination, no hernia or alterations in the IIR were detected in any of the cadavers. All the procedures were completed successfully. The mean number of U-sutures per IIR was 1.4 (range: 1-3, SD: 0.7). The mean was similar for both methods: 1.5 when using EndoClose (range: 1-3, SD: 0.8) and 1.3 when using NSLT (range: 1-2, SD: 0.5). It should be noted that for the first cadaver, a total of five sutures were necessary, three with EndoClose and two with NSLT. The characteristics of the cadavers and the findings during the procedures are summarized in the Table 1. Regarding potential adverse events of the surgical technique, complications related to the laparoscopic access, but not to the suture technique itself, were recorded in two cadavers. In one cadaver, the trocar reached the omental bursa during the placement of one of the additional portals. In another cadaver, the rumen was perforated when the first cannula was inserted. To prevent this complication, in two cadavers, part of the gas in the rumen was evacuated before the procedure using a 11 mm, 20 cm locking trocar percutaneously inserted into the rumen. 3.2. Clinical Cases 3.2.1. Case 1 A 6/7-year-old (87.5 Kg) Rasa Aragonesa ram was referred with a unilateral left IH. The hernia had appeared some weeks earlier. The ram was intended for breeding. Despite moderate posthitis, the ram had been otherwise healthy and had no history of trauma. General clinical examination and basic parameters were within normal limits. There was visible asymmetry to the scrotum, with left-sided large soft swelling in the scrotum , which could be reduced by palpation in dorsal recumbency. Ultrasonography confirmed the presence of an IH, with intestinal segments in the scrotal sac and hydrocele. Prior to surgery, food was withheld for 24 h and water was withheld for 12 h. A jugular venous catheter was placed and was used to administer flunixin meglumine (1.1 mg/kg IV, twice daily) and procaine penicillin G (15 mg/kg, once daily, IM). After the induction of general anesthesia, the ram was intubated and connected to an anesthetic machine with a system of positive pressure ventilation and oxygen supply. The ram was placed in dorsal decubitus and secured to the surgical table in the Trendelenburg position. A wide caudal abdominal area and scrotum were clipped and surgically prepared. The testicles were also surgically prepared but kept outside of the surgically draped field, placing the drapes to allow a gloved assistant to manipulate the testicles outside of the sterile area during the surgery, in case external maneuvers were necessary to reduce the hernia. Access to the abdominal cavity and placement of the laparoscopic portals were performed as described above for the cadaveric study. Laparoscopic examination confirmed the presence of an indirect IH in the left inguinal canal, with a very enlarged IIR. The hernia could be reduced with the combination of external manipulation, laparoscopic atraumatic grasping traction (Endo Clinch II and/or Endo Lung, Covidien), Trendelenburg position and capnoperitoneum (Supplementary Materials, Video S3). The LAPS of the left (herniated) IIR was carried out similarly to that described in the cadaveric study by combining both NSLT and the EndoClose device . Due to the large size of the IIR, three U-suture stitches were necessary for adequate partial closure of IIR. After knotting the percutaneous suture loops in the subcutaneous space, the skin was sutured with monofilar 2/0 USP glycinate in a simple interrupted pattern. The contralateral inguinal ring showed no signs of herniation, but a single percutaneous U-suture was performed using the same method as prophylaxis (Supplementary Materials, Video S4). There were no surgical complications other than a slight tear of the peritoneum adjacent to the IIR that occurred during the manipulations, which did not receive further intervention. The ram recovered from anesthesia without complication. The durations of anesthesia and surgery were 115 and 90 min, respectively. In the first few days after surgery, there was a marked enlargement of the scrotal sac on the left side, which progressively disappeared in the following weeks. Ultrasonography revealed a moderate amount of hypoechoic fluid but without evidence of a herniated bowel. The incisions healed properly and there was no recurrence of the scrotal hernia. After a 6 months follow-up, there was no recurrence of the hernia and the animal maintained normal sexual behavior. 3.2.2. Case 2 An 11-month-old (70 Kg) Dorper ram intended for show and breeding was referred with unilateral right IH occurring several weeks earlier, with no relevant changes after initial veterinary assessment. General clinical examination and vital parameters were within normal limits except for an asymmetry with right-sided large soft swelling in the scrotum. The hernia could be reduced externally. Conventional and color Doppler ultrasonography confirmed the presence of an IH, with intestinal segments and omentum in the scrotal sac, hydrocele and with adequate testicular perfusion . The animal underwent surgery under similar operative and perioperative conditions to Case 1. To reduce the hernia, it was necessary to perform a vigorous external scrotal massage (Supplementary Materials, Video S5). The vaginal ring was remarkably enlarged. During the procedure, after some unsuccessful LAPS attempts in the herniated side, subcutaneous and retroperitoneal emphysema developed, causing visibility to be progressively reduced, and the surgery had to be finished without being able to complete any U-sutures. Two days after reducing the hernia, the scrotal size had reduced considerably compared to admission and ultrasonography revealed a moderate amount of hypoechoic fluid but without evidence of a herniated bowel. The animal returned to his farm and re-intervention was scheduled in 15 days. However, a few days after discharge, the ram re-herniated again and the owner refused further intervention. The ram was sent to the slaughterhouse without the possibility of a necropsy. 3.2.3. Case 3 A 2/3-year-old (75 Kg) Rasa Aragonesa ram intended for breeding was referred for surgical treatment of a mild intermittent unilateral externally reducible left IH that appeared two weeks earlier. The ram was otherwise healthy and had no history of trauma. The animal was intervened under similar surgical and perioperative conditions to previous cases. The hernia was easily reduced by traction of the intestine from inside the abdomen using laparoscopic forceps. The amount of herniated bowel was more limited than in the two previous cases (Supplementary Materials, Video S6). On this occasion, a first U-suture was performed in the herniated IIR using a polyamide 1 USP suture with its own traumatic 30 mm, 3/8 circle needle, which was manually straightened and introduced percutaneously under laparoscopic control. With the aid of laparoscopic forceps, the needle was punctured outwards, creating the U-suture (Supplementary Materials, Video S7). Two additional suture loops combining the use of EndoClose and NSLT were necessary for partial closure of the IIR. The contralateral vaginal ring was closed with a single suture loop using NSLT as prophylaxis. The duration of anesthesia and surgery were 120 and 95 min. Three months after hospital discharge, no re-herniation had occurred and the animal maintained normal sexual behavior. 4. Discussion This article describes, for the first time, the LAPS technique of the IIR for repair of inguinal/scrotal hernias in rams. Traditionally, surgical treatment of IH in small ruminants has been performed by complete herniorrhaphy of the external inguinal ring, after castration. If the testicle must be spared, the surgical technique of choice is to partially close the IIR, which requires the use of laparoscopic surgery. The veterinary species in which the largest number of laparoscopic techniques have been described for this purpose is the horse, for which we can find several different approaches . The cost of laparoscopic procedures is often prohibitive for ruminant livestock. Despite this fact, different laparoscopic techniques have been reported in these animals . There are also two different case reports on rams with IH surgically treated by laparoscopic techniques. In the first of them, the authors combine different laparoscopic techniques described in other species, including the placement of polypropylene retroperitoneal meshes in a single case. Most of the techniques employed in this case require advanced laparoscopic training and/or the use of expensive consumables . In the second, most recent, case report, authors used barbed sutures in a ram. This is a technique used in horses which is simple to apply if using the EndoStitch device (Medtronic, Madrid, Spain), but can be technically more demanding if used with needle holders as described in this case report of one ram. In the present study, we used a technique based on a laparoscopic methodology developed in human pediatrics and which has also been successfully used in dogs and pigs . The advantage of this approach is that it reduces the duration of surgery, avoids the use of specific high-cost consumable materials and, fundamentally, it can be performed without the use of complex laparoscopic techniques, as it is based on extracorporeally applied knots . However, minimal laparoscopic equipment is still needed (laparoscope, laparoscopic cannula and forceps) and, although this type of material is often available in large animal hospitals (mainly for use in horses), this may be limiting in small ruminant practice. Nevertheless, and as mentioned previously, laparoscopic techniques are being developed in this species for different purposes such as artificial insemination , which may make this equipment available to some ovine veterinarians. Despite all the important advantages that laparoscopy can bring to small ruminant surgery, laparoscopic procedures in sheep present some adjunctive complications related to the placement of the first trocar, due to the possibility of accidentally puncturing the rumen or entering the omental bursa . To reduce the incidence of such unwanted events, a fasting period of at least 24 h prior to surgery is usually carried out. This could not be performed in the cadaveric study presented here and, actually, in one cadaver, there was a ruminal perforation and, in another animal, the second trocar entered the omental pouch. Such events did not occur in any of the three clinical cases, all of which included a fasting period. Additionally, regarding fasting to reduce the size of the rumen, the use of the EndoTIP (also known as Ternamian cannula) allows visually controlled insertion of this trocarless helical optical cannula and can minimize the incidence of such complications . In two of the three patients, the surgery was simple and fast to perform, without intraoperative complications except for a slight tearing of the peritoneum adjacent to the vaginal ring that occurred in Case 3. In our own experience with other species, these small peritoneal lacerations adjacent to the vaginal ring usually heal without causing problems or forming adhesions . In Case 2, another complication took place: a subcutaneous and retroperitoneal emphysema formed and prevented visibility; thus, it was not possible to safely performing the LAPS of the IIR. It could be thought that this complication is not directly related to the LAPS technique but to the laparoscopic procedure itself. However, it may also be possible that the formation of retroperitoneal emphysema was related to the incision over the inguinal ring and the first attempts to pass the needle percutaneously. In the development of a novel surgical technique, it is necessary to carry out pilot trials in order to be able to apply such technique in clinical cases, which is why many authors include in their work preliminary studies in which only experimental animals or cadavers are used . In our work, the described technique was performed on cadavers prior to the application to three clinical cases of rams with IH. As a result of the trial in cadavers, although three laparoscopic portals were placed in all of them, we believe that the procedure could be performed using only one portal for the optics, or with only one extra portal for instruments. In our hands, this was facilitated when using the EndoClose device. In the three clinical cases, however, having two work portals facilitated the hernia's reduction and LAPS maneuvers in both inguinal rings. In our opinion, the advantage of operating with only an optical portal is the main justification for using the commercial EndoClose device instead of the NSLT. However, as shown in dogs and pigs , the LAPS technique can be performed without any instrumental portal, even when using NSLT. According to our experience, the use of EndoClose does not bring any other additional benefit and increases the cost of the technique. In addition to being a more economic option, an additional advantage of NSLT over EndoClose is that it could facilitate making several entries with the needle around the margins of the ring to pass the suture several times through the same loop, thus creating a purse-string suture as described in children . This could be particularly useful when the ring is very large and requires several knots, to avoid having to pass several loops. However, a limitation of this study is that the cadaveric study was performed on animals without IH and with IIRs of smaller size than those observed in the three clinical cases. In these patients, however, we chose to use the U-suture and not the purse-string stitch described in human medicine. The rationale for this choice was to better control the tightness of the partial closure to prevent compromising testicular functionality. Thus, in Cases 1 and 3, up to three U-sutures were used for an adequate partial closure of the herniated IIR while in the original technique reported in children, only one loop is used, but with the aforementioned purse-string pattern . Works focusing on dogs and pigs using this LAPS technique also employed a U-suture, but in all cases, only one loop was used, without the need for additional sutures. This may be due to smaller IIR size in these species compared to sheep, or even to the greater experience of surgeons in previous animal studies. Another relevant point is the non-absorbable nature of the material used for suturing in this study. Several studies on laparoscopic hernioplasty in humans , dogs and horses recommend this type of non-absorbable material to maintain a mechanical closure over time, as this could provide additional security in the case of very large IIRs. Laparoscopic follow-up at 4 weeks in such studies showed no deleterious effects derived from the use of non-absorbable sutures such as infections, adhesions or other foreign body reactions . However, good results have also been obtained in porcine species with this technique, using absorbable sutures . Further studies can help to clarify the most suitable material in the longer term. The clinical cases described here presented acquired hernias for which it was not possible to identify a traumatic event that caused them. However, acquired traumatic scrotal hernias are usually much more common in rams than congenital hernias . Although the heritability of this condition is not well-understood, it is imperative to properly inform owners of affected animals if they intend to use them as breeding rams . In those cases where reproductive activity is to be maintained after surgery, it is imperative that the partial closure of the canal does not affect testicular perfusion and functionality. In the case described by Daniel et al. in 2015 , the animal was previously castrated from the unaffected testicle and sperm production of the affected testicle could be monitored up to 5 months post-surgery. In our Cases 1 and 3, a specific study of reproductive functionality was not carried out. The impossibility of long-term reproductive monitoring, the non-blinded interpretation of results, and the small number of animals constitute the main limitations of our study. Another limitation to this study was that a control group was not included to compare the outcome of the new technique. However, it should be noticed that there are currently no standardized or preferred techniques for partial closure of IIRs in rams, with only two single-animal reports so far. Therefore, this study is presented as a first step to describe the technique with the aims of developing it further and comparing it with other methodologies according to the advancement of the field. In addition to the value of the LAPS methodology for small ruminant surgery, our results open up the possibility to use this technique in foals with congenital IH. It should be considered that some of the techniques and devices developed for adult horses have not yet been tested in foals or have only been described for standing surgery , which is unfeasible with foals. It should also be noted that procedures under general anesthesia in neonates and foals have a higher anesthetic risk than in adult horses , so any technique that simplifies the procedure and shortens the intervention is desirable. The potential application of the LAPS technique in equine neonates requires studies in such animals, with a large number of cases to study the efficacy and possible influence on long-term testicular activity. 5. Conclusions Laparoscopically assisted percutaneous IIR suturing is a simple and feasible surgical procedure for rams with inguinal hernias when preservation of testicles is preferred. This laparoscopic hernioplasty technique can be considered as an alternative to herniorrhaphy with orchiectomy in rams. However, larger numbers of cases, as well as prospective, longer and more comprehensive follow-up would be required to evaluate long-term safety and effectiveness. Acknowledgments The authors would like to thank the staff of the Ruminant Clinic Service (SCRUM) of the Veterinary Hospital of the University of Zaragoza, Spain, for their collaboration in the study, referral of some cases and some patients' follow-up. The authors would also like to thank Jose L Mendez, DVM, MS, DACVS, PhD, for his help in performing the techniques on some of the cadavers and for his contribution to the initial concept of laparoscopically assisted percutaneous closure. We would also like to thank Maria Vazquez for drawing Figure 1. Supplementary Materials The following supporting information can be downloaded at: Video S1: Main steps of the needle suture loop technique (NSLT) for laparoscopically assisted percutaneous suture of the right internal inguinal ring in a cadaver. Video S2: Procedure to verify the adequacy of a right internal ring hernioplasty in a cadaver. A blunt laparoscopic trocar can be inserted through an incision in the scrotum and tunica vaginalis before the suture is tightened. After tightening and knotting the suture on the outside, it is not possible. Video S3: Laparoscopy of case 1. The hernia could be reduced with the combination of external manipulation, laparoscopic atraumatic grasping traction, Trendelenburg position and capnoperitoneum. Video S4: Laparoscopy of Case 1. The contralateral (right) internal ring showed no signs of herniation, but a single percutaneous U-suture was performed. In this occasion, a needle of 20 G and 70 mm was placed under laparoscopic control as a guide to insert the EndoClose device. Video S5: Laparoscopy of Case 2. To reduce the hernia, traction from the inside using laparoscopic forceps was unsuccessful and it was necessary a vigorous external scrotal massage. The hernia contents were found to include abundant loops of small bowel, omentum and fluid. Video S6: Laparoscopy of Case 3. The hernia was easily reduced by traction of the intestine from the inside with laparoscopic forceps. The amount of herniated bowel was less than in previous cases. Video S7: Laparoscopy of Case 3. A first U-suture was performed using a polyamide 1 USP suture with its own traumatic, 30 mm, 3/8 circle needle, stretched manually in order to obtain a reasonably straight needle and introduced percutaneously under laparoscopic control. Two additional U-sutures combining the use of EndoClose and needle suture loop technique were necessary for partial closure of the inguinal ring. Click here for additional data file. Author Contributions Conceptualization, F.J.V., A.R. and A.V.; data curation, F.J.V., A.R., S.F., L.B. and A.V.; formal analysis, F.J.V., A.R., S.F., L.B. and A.V.; investigation, F.J.V., A.R., S.F., L.B. and A.V.; methodology, F.J.V., A.R., S.F. and A.V.; project administration, A.R.; supervision, F.J.V. and A.V.; writing--original draft, F.J.V.; writing--review and editing, F.J.V., A.R., S.F., L.B. and A.V. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The animal study protocol was approved (Project Licences PI63/22 and PI66/22, 22 January 2022) by the Ethics Committee for Animal Experiments from the University of Zaragoza. Informed Consent Statement For clinical cases, informed owner (or an authorized agent for the owner) consent was obtained before enrolling any ram. Data Availability Statement Data are contained within the article or supplementary material. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Scheme of laparoscopic portal placement. Red circle: laparoscope portal, placed 5 cm cranial to the prepuce and 5 cm to the right of the midline. Green circles: instrumental portals, placed 10-15 cm cranial to each inguinal ring. Blue dotted lines: inguinal rings. Figure 2 Needle suture loop technique (NSLT) for laparoscopically assisted percutaneous suture of the right internal inguinal ring in a cadaver. (Top): 12 G 80 mm needle, with a suture loop through it, inserted through the skin incision into the abdominal cavity under laparoscopic control; asterisk: internal inguinal ring; black arrow: spermatic cord. (Bottom): distal end of a 0 USP polyamide suture introduced into the abdomen through the needle and passed into the initial loop with the assistance of laparoscopic forceps. Figure 3 Case 1: Rasa Aragonesa ram with large left scrotal hernia. Figure 4 Case 1: Laparoscopically assisted percutaneous suture using the EndoClose device in the first clinical case. (Top left): aspect of the left vaginal ring after hernia reduction. (Top in the middle): a needle was inserted percutaneously into the ventral aspect of the vaginal ring to introduce a 0-USP polyamide suture through it. (Top right): the EndoClose device inserted into the dorsal side of the vaginal ring was used to grasp and exteriorize the suture, completing the U-suture. (Bottom left): with the help of laparoscopic forceps, the suture is positioned to be held by the notched tip of the Endoclose. (Bottom in the middle): externalizing the suture to create the second U-suture; a slight peritoneal tear can be seen due to the manipulations on the cranial side of the vaginal ring. (Bottom right): final laparoscopic appearance of the inguinal ring after placement of three laparoscopically assisted U-sutures. Figure 5 Pulsed Doppler ultrasonography of right testicle in Case 2, showing perfusion parameters measured in an intratesticular artery. Within the ultrasonographic window, the testicle (asterisk) with herniated omentum and the bowel (arrows) and fluid (arrowhead) can be seen. animals-13-00836-t001_Table 1 Table 1 Characteristics of ram cadavers used in cadaveric study and findings during procedures with each method employed for laparoscopically assisted percutaneous internal ring suturing. Order Age (Months) Weight (kg) Incidences Related to Portal Placement EndoClose a NSLT b Total U Sutures Side U-Sutures Side U-Sutures 1 54 75 - Right 3 Left 2 5 2 48 75 1st portal: rumen puncture Left 1 Right 2 3 3 60 65 Previous ruminal trocar Right 1 Left 1 2 4 60 90 2nd portal: into omentum Right 2 Left 1 3 5 82 65 Previous ruminal trocar Right 1 Left 1 2 6 36 85 - Left 1 Right 1 2 Mean 56.7 75.8 1.5 1.3 2.8 SD 15.3 10.2 0.8 0.5 1.2 Total 9 8 17 a Grasping the suture with EndoClose.; b NSLT: Grasping the suture with a loop of polyamide suture passed thought a 12 G 80 mm needle. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000227 | Disentangling phylogenetic and phylogeographic patterns is fundamental to reconstruct the evolutionary histories of taxa and assess their actual conservation status. Therefore, in this study, for the first time, the most exhaustive biogeographic history of European wildcat (Felis silvestris) populations was reconstructed by typing 430 European wildcats, 213 domestic cats, and 72 putative admixed individuals, collected across the entire species' distribution range, at a highly diagnostic portion of the mitochondrial ND5 gene. Phylogenetic and phylogeographic analyses identified two main ND5 lineages (D and W) roughly associated with domestic and wild polymorphisms. Lineage D included all domestic cats, 83.3% of putative admixed individuals, and also 41.4% of wildcats; these latter mostly showed haplotypes belonging to sub-clade Ia, that diverged about 37,700 years ago, long pre-dating any evidence for cat domestication. Lineage W included all the remaining wildcats and putative admixed individuals, spatially clustered into four main geographic groups, which started to diverge about 64,200 years ago, corresponding to (i) the isolated Scottish population, (ii) the Iberian population, (iii) a South-Eastern European cluster, and (iv) a Central European cluster. Our results suggest that the last Pleistocene glacial isolation and subsequent re-expansion from Mediterranean and extra-Mediterranean glacial refugia were pivotal drivers in shaping the extant European wildcat phylogenetic and phylogeographic patterns, which were further modeled by both historical natural gene flow among wild lineages and more recent wild x domestic anthropogenic hybridization, as confirmed by the finding of F. catus/lybica shared haplotypes. The reconstructed evolutionary histories and the wild ancestry contents detected in this study could be used to identify adequate Conservation Units within European wildcat populations and help to design appropriate long-term management actions. European wildcat Felis silvestris divergence times glacial refugia mitochondrial DNA mito-nuclear discordances phylogeny phylogeography This research received no external funding. pmc1. Introduction Biogeographic and phylogeographic patterns are key factors in clarifying the evolutionary histories of taxa and identifying appropriate conservation management units (ESU and MU ) to be long-term preserved . Quaternary climate oscillations have significantly affected the current composition, distribution, and genetic diversity of species, subspecies, and populations, with local extinctions, replacements, and re-expansions with secondary contacts within the Palaearctic region . Additionally, the current Eurasian taxa distribution and genetic structure have been further altered by more recent anthropic factors, such as natural habitat fragmentation, domestication, and alien species invasions, which are heavily impacting biodiversity and ecosystem equilibria . The potential consequences of such past environmental changes and recent intense anthropic activities on the survival of natural taxa have been extensively investigated through a number of molecular studies, which allowed to reconstruct complex phylogeographic structures , identify local adaptations , trace migration routes , detect domestic or allochthonous introgression signals , and design sound conservation strategies, especially for populations affected by protracted demographic declines . Among Eurasian felids, the European wildcat (Felis silvestris), heterogeneously distributed throughout Europe, Caucasus, and Turkey, represents a challenging conservation priority, potentially threatened by habitat loss and anthropogenic hybridization, whose taxonomy and systematics are, however, still debated . Indeed, based on genetic and biogeographic information, Driscoll et al. included the European wildcat among the five subspecies of Felis silvestris (F. s. silvestris, F. s. lybica, F. s. catus, F. s. ornata, and F. s. cafra). Conversely, Kitchener et al. recently reclassified the European taxa as three separate species: the European wildcat, Felis silvestris, the African wildcat, Felis lybica, and the domestic cat, Felis catus. Fossil records and archaeological remains dated the first appearance of the European wildcat in the continent back to 450,000-200,000 years ago . Since then, both Pleistocene natural climatic oscillations and anthropogenic events, such as human persecution , deforestation, habitat modifications, and local decline of major prey , have continuously shaped current distribution patterns and genetic structure of the species . In particular, the European wildcat genetic structure has been further muddled by anthropogenic hybridization and subsequent introgression with domestic cats, which were human-spread from the Middle East through Europe after their domestication from the African wildcat . To shed light on the conservation status of the taxon, the European wildcat population genetic structure and patterns of domestic admixture have been deeply addressed, principally using nuclear molecular (STR and SNP) markers, detecting five main biogeographic groups and variable degrees of domestic introgression throughout Europe . However, only a few molecular studies have investigated phylogenetic and phylogeographic patterns of Felis silvestris in Europe so far, mainly using informative mitochondrial portions (such as the Control Region or the NADH Dehydrogenate Subunits) to distinguish domestic cat from European wildcat lineages, detecting the rough presence of a continental and Mediterranean clade among the latter . However, these studies also hightailed the occurrence of anomalous cases of F. catus/lybica mitochondrial lineages among nuclear-pure wildcat individuals, which might be interpreted as (i) the legacy of ancient natural , (ii) Neolithic human-mediated hybridization events between European and African wildcat populations, or (iii) a signal of a more recent anthropogenic admixture between European wildcats and domestic cats . Nevertheless, only a small number of individuals were typed in these studies, and the analyzed samples were collected across restricted geographical areas. Thus, an extensive and exhaustive analysis of the European wildcat mitochondrial diversity patterns across the continent is still missing and would be necessary to disentangle the complex evolutionary framework of the species and better understand the role played by natural and anthropogenic drivers. In this study, therefore, we analyzed variation patterns of a portion of the mitochondrial NADH dehydrogenase subunit 5 in a geographically representative set of European wildcat and domestic cat individuals with the scope to (1) accurately describe European wildcat phylogenetic and phylogeographic patterns in Europe, (2) date back divergence times among the main haplogroups in the European wildcat phylogenetic history, and (3) evaluate different likely biogeographic scenarios to clarify the origin of shared haplotypes between wild and domestic cats. 2. Materials and Methods 2.1. Sampling A total of 705 high-quality DNA cat samples, opportunistically collected from found dead animals between 1998 and 2010 in 12 sub-regions belonging to six European biogeographic macro-regions , were selected from the ISPRA Felis DNA biobank . Sampled individuals had been previously identified morphologically by collectors according to phenotype, life history traits, and biometric indices . Samples had also been previously genotyped at 31 microsatellites (STR) loci and genetically classified as domestic (Felis catus), wild (Felis silvestris), or putative wild x domestic admixed cats through Bayesian clustering analyses based on an assignment threshold of posterior probability proportion to belong to the wildcat cluster qi = 0.90 (Supplementary Table S1). According to these criteria, the selected samples were re-classified into 420 European wildcats, 213 domestic cats, and 72 putative admixed individuals (see Mattucci et al. for details about sampling, DNA extraction, genotyping, and assignment methods). Due to the high level of domestic introgression spread in Scotland and Hungary, felid samples from these two sub-regions were mainly represented by wild x domestic admixed cats . 2.2. Mitochondrial DNA Sequencing and Haplotype Identification Selected samples were sequenced for a portion of 835 bp of the mitochondrial NADH dehydrogenase subunit 5 (ND5; nucleotides 13,149-13,983 mapped on the mitochondrial genome of the domestic cat; NCBI Reference Sequence NC001700). This mtDNA region is particularly suitable for phylogeny reconstructions, because of the absence of nuclear mitochondrial segments (numts) and its reduced homoplasy, and is highly discriminating, since it contains seven diagnostic mutations useful to distinguish the European wildcat (F. silvestris) from the domestic/African cat (F. catus/lybica) lineages . Fragments were amplified using Polymerase Chain Reaction (PCR) primers F2B (5'-TGCCGCCCTACAAGCAAT-3') and R3B (5'-TAAGAGACGTTTAATGGAGTTGAT-3') . Each 10 mL PCR reaction contained 2 mL of DNA (c. 50 ng), 0.8 mL of 10X Taq Buffer advanced (Eppendorf) with self-adjusting Mg2+ (Eppendorf), 0.80 mL of 0.2% bovine serum albumin (Sigma-Aldrich, St. Louis, MO, USA), 0.36 mL of 2.5 mM dNTPs (Eppendorf), 0.15 mL of each 10 mM primer solution (Bionordika, Solna, Sweden), 0.04 mL of 5 U/mL HotStart Taq polymerase (Eppendorf, Tokyo, Japan), and 5.70 mL of purified water (Eppendorf, Milano, Italy). PCRs were performed in a Veriti Thermal Cycler (Life Technologies, Carlsbad, CA, USA) with the following thermal profile: 94 degC for 15 min for initial denaturation and Taq activation, followed by 50 cycles of 30 s at 94 degC, 60 s at 55 degC and 60 s at 72 degC. The PCR cycling was followed by a final extension for 10 min at 72 degC. PCR products were stored at 4 degC and then purified by exonuclease digestions (1 mL of EXO-SAP per sample, incubated at 37 degC for 30 min, then at 80 degC for 15 min). The purified amplicons were Sanger-sequenced in both directions. Each 10 mL reaction contained 1 mL of amplified DNA, 1 mL of BigDye v1.1 (Life Technologies), 0.2 mL of either the forward or reverse primer, and 7.8 mL of purified water. Sequencing was performed in a Veriti Thermal Cycler with 25 cycles of 10 s at 96 degC, 5 s at 55 degC, 4 min at 60 degC and storage at 4 degC. The purified products were added with 10 mL of Hi-DI formamide (Life Technologies), denatured for 3 min at 95 degC, and analyzed on an Applied Biosystems (ABI) 3130 XL DNA Analyzer. 2.3. Phylogenetic Analyses and Estimates of Divergence Times The 705 cat NAD5 sequences were aligned and corrected in SeqScape v2.5 (Life Technologies) and used to build a cat NAD5 dataset, which also included other 10 different European wildcat homologous sequences (accession numbers: EF587158, EF587164, EF587168, EF587166, EF587170, EF587169, EF587171, EF587156, EF587162, EF587159; ), retrieved from GenBank. All the 715 produced and downloaded cat sequences were consequently trimmed into equal sequences of 669 bp (positions 13,243-13,911) to maintain full-length, double-stranded, high-quality sequence data across all samples, using BioEdit v7.1.11 . Identical haplotypes were identified and collapsed using DnaSP v5.10.01 , and possible correspondences with haplotypes already published in GenBank were checked using Blast . The final dataset of unique cat NAD5 haplotypes was then used to perform all the downstream diversity, phylogeographic and phylogenetic analyses. Haplotype (Hd) and nucleotide diversity (p) were computed using DnaSP. The best nucleotide substitution model scheme was computed in PartitionFinder v2 by the Bayesian information criterion (BIC), and, subsequently, three phylogenetic trees were constructed through different computational approaches: (i) the neighbor-joining (NJ, ) method, using Smart Model Selection (SMS, ) algorithms implemented in Mega v11.0 and performing 10,000 random bootstrap replications; (ii) the maximum-likelihood method (ML, ) implemented in Phyml v3.0 with the heuristic search by topological rearrangement of an initial tree (Near-Neighbor-Interchange) and 5000 random bootstrap replications; (iii) the Bayesian method (BT) implemented in Beast v2.1.3 , which further allowed to estimate divergence times among nodes. Due to the strong relationship between taxa, a strict molecular clock model with a fixed mean substitution rate (2.28 x 10-8/site/year ) and constant population size as coalescent priors were selected. The Bayesian posterior probabilities (BPPs), as well as the high posterior densities for the node ages (HPDs), were extrapolated by performing three independent MCMC runs of 100,000,000 steps with a burn-in period of 10,000,000 steps and picking genealogies every 2000 steps. The results of the three chains were simultaneously analyzed in Tracer v1.7 . The corresponding portion of the ND5 sequence of Felis margarita retrieved from GeneBank (Accession number: EF587034) was used as an outgroup in NJ and ML tree reconstructions. Conversely, the BT tree was calculated without the inclusion of an outgroup, as suggested by Beast developers , and the tree rooting point was estimated using as a prior calibration point the time interval in which the common ancestor between F. silvestris and F. catus/lybica likely coalesced (230,000-173,000 years ago ). Each supported node was annotated with bootstrap values for NJ and ML trees and the highest posterior density (HPD) for the BT tree (e.g.: NJ/ML/HPD). 2.4. Demographic Analyses A median-joining (MJ) network analysis was performed in Network v4.6 (Fluxus Technology Ltd., Stanway, UK ) to corroborate tree reconstructions, and investigate haplotypes relationships, frequencies, and geographic repartitions, using an e = 10 and transversions/transition weighting of 3:1. Haplotype pairwise genetic distances among cat taxa and cat biogeographic clusters, assessed with an analysis of molecular variance (AMOVA), and the phST and phSC indexes for genetic differentiation , were computed in Arlequin v3.5.1.3 , running 10,000 permutations to evaluate the significance of each parameter. Further spatial analysis of molecular variance (SAMOVA) was performed using Samova v2.0 , which defines clusters of geographically homogeneous populations, based on an a priori definition of the number of K groups, and uses a simulated annealing procedure to maximize the proportion of total genetic variance between groups with an AMOVA approach. We tested a different number of groups (with K from 2 to 9), each time with the simulated annealing process repeated 10,000 times, starting with a different partition of the population samples into the K groups. The selection of the best K-repartitions was based on the highest significant values of the FCT genetic differentiation index. FCT estimates differentiation among those groups of populations. The closer FCT is to 1, the more divergent the groups are from each other. 2.5. Approximate Bayesian Computation Analyses The Approximate Bayesian Computation (ABC) simulations , implemented in Diyabc v2.1.0 , were run to model plausible demographic scenarios and estimate divergence times (in generations). We performed two types of ABC analyses: (a) considering only populations carrying wildcat mitochondrial haplotypes ; and (b) considering populations showing mito-nuclear discordance (see Results). In details, to avoid over-computation, we designed the smallest number of evolutionary scenarios using as prior populations the spatially geographical and genetically homogeneous clusters found through SAMOVA analyses. Successively, we simulated alternative evolutionary hypotheses using haplotype distribution and divergence times estimated from the reconstructed Bayesian phylogeny (see Results) and modeled population dynamics, taking into account the main phylogeographic findings reported in the literature . Therefore, we tested four demographic scenarios for the wildcat haplotypes , hypothesizing that the four clusters split sequentially (scenarios 1 and 3) or simultaneously (scenarios 2 and 4) and that Cluster 4 diverged by isolation (scenarios 1 and 2) or followed a gene flow with other European populations (scenarios 3 and 4). The haplogroup, including wildcats showing mito-nuclear discordances, was analyzed by testing three different scenarios: (a) the three clusters split in recent times from few common ancestral haplotypes (scenario 1); (b) the three clusters split in different sequential evolutionary events (scenario 2); (c) same as scenario 2 but considering longer coalescence time (scenario 3). We ran 4 x 106 simulations for each scenario using prior uniform distributions of the effective population sizes and time parameters with the gamma-distributed mutation model with Gamma shape = 4.0. Scenarios were compared by estimating posterior probabilities using the logistic regression method using 1% of the simulated datasets. For the best models, posterior distributions of the parameters were estimated with a logit-transformed linear regression on the 1% simulated datasets closest to the observed data. Scenario confidence was evaluated by comparing observed and simulated summary statistics. Finally, the goodness-of-fit of the posterior parameters for the best-performing scenarios was tested via the model checking option with default settings, and significance was assessed after Bonferroni correction for multiple testing. 3. Results Haplotype alignment did not show any indels or stop codons and the aminoacidic sequence was concordant with the domestic cat ND5 protein sequence (NCBI Reference Sequence NC001700). Thus, we excluded the amplification of numts or pseudogenes. After regrouping procedures, we identified 29 haplotypes among the 715 sequences, counting 32 polymorphic sites, including 23 parsimony informative sites, with a total haplotype diversity Hd = 0.862 +- 0.006 and a nucleotide diversity p = 0.870 +- 0.013 (Table 1). We compared the resulting haplotype sequences with the NCBI nucleotide database using the Blast algorithm founding 12 new unpublished haplotypes (Supplementary Table S2). 3.1. Phylogenetic Analyses and Divergence Time Estimates The best fit evolutionary model for the 29-haplotype alignment was Kimura's two-parameter (K80 ) model with invariable sites (I = 0.80) for the first and second codon positions, whereas the Hasegawa, Kishino, and Yano (HKY ) model with a gamma distribution and four discrete categories was selected for the third codon position. The NJ, ML, and BT phylogenetic trees showed very concordant topologies for the main clades ; thus, we described in detail directly the topology of the tree generated by Beast, which presented posterior probabilities of the main internodes > 0.90 . In the BT tree, haplotypes were clearly split into two main and strongly supported lineages (node 1, 100/100/1), diverging 197,500 years ago (95% HPD 173,002-226,274 years ago): (i) lineage D, including 15 haplotypes, shared in 448 (62.3%) individuals and (ii) lineage W, including 14 haplotypes, shared in 267 individuals (37.7%) (Table 1). Haplotypes were separated into three main categories according to the previous 31-STR Bayesian assignment tests performed by Mattucci et al. : (i) category "d" included haplotypes found only among domestic cats; (ii) category "dw" included haplotypes found either in domestic, wild or putative admixed individuals; and iii) category "w" included haplotypes found only among wildcats and putative admixed individuals. Lineage D included eight haplotypes, identified by the prefix "d", exclusively detected in 25 domestic cat genotypes, and other seven haplotypes, identified by the prefix "dw", found in 174 wildcat (41.4% of the wild), 188 domestic cats, and 61 putative admixed (84.7% of the wild) genotypes (Supplementary Table S3). In this lineage, we found the first highly supported split (node 2, 100/88/0.99) dating back about 80,000 years ago (95% HPD 31,561-145,850 years ago), distinguishing two major clade groups, I-II and III . A second split occurred at node 3 (63/65/0.54), about 50,000 years ago (95% HPD 16,756-97,189 years ago), separating clades I and II . A final third split appeared at node 4 (61/64/0.92), dating back 37,700 years ago (95% HPD 11,992-76,931 years ago) and dividing sub-clades Ia and Ib . Interestingly, most wild individuals showing discordant mtDNA variants (130 wildcats) shared dw4 and dw6 haplotypes within sub-clade Ia, and all 61 putative admixed individuals carried dw haplotypes. Lineage W included 14 haplotypes, identified by the prefix "w", and shared by 246 (58.6%) wildcats, 11 (15.3%) putative admixed individuals, and all the 10 GeneBank European wildcat reference sequences. It presented only one main supported diverging point (node 5, 96/100/1), dated back to 62,400 years ago (95% HPD 21,860-118,910 years ago), separating two clades, IV and V (see Supplementary Material and Supplementary Table S3 for details). 3.2. Phylogeographic Analyses of European Wildcat and Putative Admixed Individuals MJ network, reconstructed using the entire 29-haplotype alignment, was highly concordant with the topology of the BT tree , identifying two main haplogroups (D and W), which were clearly separated by seven diagnostic polymorphisms, previously described by Driscoll et al. , though one of them (D) included seven domestic-wild shared haplotypes . The AMOVA (Table 2), performed considering European wildcats, domestic cats, and putative admixed cats as different groups, detected a higher proportion of variation within (63.3%) than among (36.7%) populations and a significant differentiation index phst = 0.37 (p < 0.01). However, to avoid that domestic cat distribution, strongly linked to human activities, might inflate estimates, the initial dataset was pruned from samples genetically assigned to the domestic cat group and phylogeographic analyses were focused on wildcat and putative admixed populations. Thus, a further MJ network was reconstructed using ND5 sequences from 430 wildcats and 72 putative admixed individuals, corresponding to 21 haplotypes and characterized by 26 polymorphic sites and 21 parsimony informative sites . In the network, the presence of two main haplogroups, significantly differentiated (phST = 0.97, p < 0.01; Table 2) was still evident: (i) DW, cleaned from "d" haplotypes, including 174 wildcats and 61 putative admixed cats; and (ii) W, including 256 wildcats and 11 putative admixed individuals . Haplogroup DW showed a split, roughly corresponding to node 2 of the BT tree , which separated clades I-II and III. In particular, sub-clade Ia included haplotype dw4, which was the most frequent within haplogroup DW, was found in 146 individuals, and showed a spread distribution across central and southern Europe . Haplogroup W showed a split, roughly corresponding to node 5 of the BT tree , which separated a clade IV, shared among 85 individuals, most of them collected in Italy (63.2%) and the Iberian peninsula (18.2%) macro-regions and a clade V, shared among 182 individuals, mostly collected in Central Europe (62.6%), and in the Balkan (23%) macro-regions (see Supplementary Material and Supplementary Table S3 for details). The spatial analysis of molecular variance (SAMOVA) showed that the most statistically-supported geographic partition within haplogroup W corresponded to K = 4 population groups, with an overall FCT = 0.64 (p < 0.01) and 63.2% of variation explained among the detected repartitions. The four groups included Italy and South-Eastern Europe (Cluster 1), Central and North-Eastern Europe, the Balkans (Cluster 2), Scotland (Cluster 3), and the Iberian Peninsula (Cluster 4) . Conversely, haplogroup DW was optimally structured in K = 3 clusters, including Scotland (Cluster 1), the Iberian Peninsula (Cluster 2), and the remaining European populations (Cluster 3) , with a lower overall FCT = 0.28 (p < 0.05) and most of the variation explained within populations (63.06%). The independent AMOVAs performed considering six biogeographic repartitions , yielded concordant results but with a slightly lower proportion of variation explained among macro-regions (58.24%) for the haplogroup W and a higher proportion of variance within populations (82.8%) in haplogroup DW (Table 2). 3.3. Demographic Analyses A weak significant sign of population expansion was detected in the domestic cats of lineage D with a near bell-shaped curve in the mismatch plot , a Tajima's D = -0.413 (p = 0.078) and a Fu and Li's F = -2.337 (p < 0.05) (Table 2). The mismatch distribution curve and the slightly significant negative values of Tajima's and Fu and Li's estimators suggested a low degree of population expansion also for lineage W (Table 1). However, within this haplogroup, only Italy and the Balkan macro-regions presented an increasing trend in the mismatch plot consistent with significant negative values of Tajima and Fu and Li's statistics , although these values were lower than two, suggesting caution in considering a hypothesis of actual expansion . Among dw haplotypes, only those of Central Europe showed traces of an actual expansion trend with significant negative values of the statistics (Tajima's D = -2.002; p < 0.01 and FU and Li's F = -1.106; p < 0.05; Table 1) and a low peak in the mismatch plot . 3.4. Approximate Bayesian Computation Analyses ABC simulations for haplogroup W provided the best support for scenario 4 with a posterior probability of 0.372 (95% C.I. 0.000-0.796). Under this scenario, the median values of the divergence time showed that Cluster 1, Cluster 2, and Cluster 3 started isolating about 40,800 generations ago (5-95% quartile: 13,900-53,600). Considering a wildcat generation time of two years , the time from the most recent common ancestor (TMRCA) of these populations was estimated at about 81,600 years ago (5-95% quartile: 27,800-107,200 years ago). The following admixture event between Cluster 1 and Cluster 2 contributed to generating Cluster 4 approximately 8920 years ago. Simulations on the DW haplotype showed the best posterior probability for scenario 1 (simultaneous splitting in recent times) with a posterior probability of 0.748 (95% C.I. 0.367-1.000). Median values of the divergence time from TMRCA suggested 540 generations ago (5-95% quartile: 42.2-5250), corresponding to about 1080 years ago (5-95% quartile: 84.4-10,500). 4. Discussion Pleistocene climate oscillations significantly shaped the biogeographic patterns and genetic structure of many mammal species within the Palaearctic region . Several examples of shifts in the distribution and genetic composition of mammal populations following glacial and sea-level cycles have been clearly described, highlighting how recurring east-west colonization waves introduced new genetic variants, and subsequent post-glacial recolonizations from Mediterranean and extra-Mediterranean refugia further modified their genetic makeup . In addition, for some species affected by anthropogenic hybridization, such as the European wildcat (Felis silvestris), the wolf (Canis lupus), or the wild boar (Sus scrofa), the genetic mosaic has been further altered by the introgression of domestic variants . Therefore, here we describe phylogenetic and phylogeographic patterns obtained by analyzing a diagnostic fragment of the mtDNA on a wide sampling of European wildcats collected across Europe to (i) detect clear signs of genetic differentiation between central and southern European wildcat populations, likely resulting from glacial isolation and consequent post-glacial recolonization processes, and (ii) disentangle the origin of shared haplotypes between wild and domestic cats. 4.1. Phylogenetic Patterns Although based on partial ND5 sequences, our phylogenetic reconstructions on European wild and domestic cats well reflected their evolutionary relationships confirming previous studies on larger portions of the mitochondrial DNA , as well as entire mitogenomes . Indeed, we detected four main F. catus/lybica haplogroups (D: Ia, Ib, II, and III), showing an overall high level of haplotype diversity (0.735 +- 0.018) and originating about 80,000 years ago. According to Driscoll et al. , such clades might reflect the multiple origins of the F. catus/lybica lineage, whose estimated coalescence time, although older, is largely included within our confidential intervals. Whitin F. catus/lybica lineage, clades I and II showed a higher haplotype richness and frequency among samples (in particular, they included 58.2% of all domestic cats). Such haplogroups could be roughly associated with lineages A/B, previously found by Driscoll et al. and Ottoni et al. , which represent the Near Eastern Felis contribution to the mtDNA pool of present-day domestic cats. On the other hand, clade III, showing a basal phyletic position, might correspond to lineage C described by Driscoll et al. and Ottoni et al. , which includes north African wildcat haplotypes (possibly of ancient Egypt derivation) later spread in Europe . Concordant results with previous studies were further found for the F. silvestris lineage W, which showed two main clades, IV and V, dating back about 62,400 years ago. Similar divergent times and phylogenetic patterns have been observed also in other species, such as the pine marten (Martes martes) and the wolf (Canis lupus) and might be the result of Pleistocene climatic oscillations on mammal population distribution and evolution . 4.2. Phylogeographic Patterns A spatial analysis of molecular variance (SAMOVA) was performed to clarify phylogeographic patterns within the European wildcat lineage W, showing that its haplotypes were spatially clustered into at least four main geographic groups roughly concordant with the biogeographic regions previously detected analyzing nuclear markers : (1) a South-Eastern European cluster, spanning from Italy to Hungary; (2) a Central European cluster, spanning from the Italian and Balkan Alps to Germany; (3) a cluster including the isolated Scottish population; 4) a cluster including the Iberian population. In particular, Cluster 1 showed the overall lowest genetic variability. However, further analyses, including additional wildcat samples from other unsampled and formerly in contact with eastern Countries, such as Anatolia, might reveal increased genetic variability levels and shed light on the possible contributions of such populations in shaping the current European wildcat evolutionary history in eastern European populations, such as that living in Hungary. This cluster was mainly represented in clade IV with (a) the dominant haplotype w1, shared at low frequencies also with the Iberian Peninsula wildcats, which could be the result of a colonization wave from eastern Europe during glacial periods and subsequent isolation south of the Alps, which acted as a natural barrier to gene flow , and (b) the presence of a private haplotype w5 in Sicily, that could result from the long-lasting isolation of the Island from the Peninsula . These recolonization and subsequent isolation patterns are further confirmed by the presence of shared mtDNA haplotypes in other mammal species, such as the pine marten (Martes martes) , the red deer (Cervus elaphus) , the roe deer (Capreolus capreolus) , and the brown bear (Ursus arctos) in southern Europe. Cluster 2 showed a higher genetic variability, and was mainly represented in clade V, characterized by the predominance of haplotype w4, which might have originated in extra-Mediterranean or in the Dinaric-Alpine refugia and successively widespread in Central Europe, as hypothesized through molecular studies carried out also on the hedgehog (Erinaceus europaeus) , the Eurasian lynx (Lynx lynx) and the red deer (Cervus elaphus) and confirmed by the absence of Pleniglacial wildcat archaeological findings . Cluster 3 showed a single unique haplotype w3, which might be the legacy of the mtDNA gene pool of a continental wild ancestor which migrated to Britain via land bridge approximately 10,000 years ago and originated the Island population, which successively experienced recurrent bottlenecks during glacial maximums, more recent demographic declines, and a compromising anthropogenic admixture with domestic cats . Finally, Cluster 4 showed a) the balanced presence of haplogroups IV and V, which might derive from the Pleistocene population migration waves from Central Europe, as supported also by ABC analyses, and b) the occurrence of three private haplotypes, w9 and w12 in Spain and w8 in Portugal, which might have originated during the subsequent isolation south of the Pyrenes . 4.3. Mito-Nuclear Discordance and Evolutionary Hypotheses Our phylogenetic and phylogeographic history of the European wildcat assessed by partial mitochondrial sequences revealed the widespread presence of haplotypes shared between wild and domestic cat populations. Indeed, a consistent proportion of individuals previously assigned to the wildcat population through STR Bayesian clustering analyses were included in the mitochondrial lineage D. Cases of Felis mito-nuclear discordances have been already described and generally attributed to recent F. catus mitochondrial introgressions, which may have likely eroded domestic ancestry at the nuclear loci after a few backcrossing generations , leaving exogenous traces only at the mtDNA or at a small portion of the nuclear genome . Accordingly, our mtDNA data showed several shared haplotypes (dw1, dw2, dw3, dw5, dw7), mostly frequent within domestic cats, which seem to have recently differentiated and simultaneously split about 1000 years ago, as further revealed by the best ABC evolutionary scenario, supporting the hypothesis of an F. catus introgression. However, other two shared haplotypes, belonging to the D subclade Ia (dw4 and dw6), mostly frequent within wildcats, seem to have originated about 37,000 years ago, which, according to the last available archaeological and genetic findings, long pre-dated any evidence for cat domestication , thus suggesting their possible natural F. lybica derivation. This latter hypothesis fits well with the scenario of a late Pleistocene European wildcat migration toward the Levant and Anatolia regions already occupied by F. lybica populations . Such a syntopic event might have promoted a natural inter-taxon gene flow introgressing F. lybica mitochondrial signatures in some European wildcat individuals . A possible female-biased directionality of the admixture patterns might justify the high numbers of F. catus/lybica mtDNA hyplotypes found in the European wildcats analyzed in this study, though this hypothesis should be confirmed or denied by further Y-chromosome haplotype analyses. 5. Conclusions In this study, using a short but highly diagnostic portion of the mtDNA, we provide the first exhaustive description of the European wildcat phylogenetic and phylogeographic structure across the entire species' range in the continent. Our results suggest the presence of at least three main continental biogeographic clusters, roughly corresponding to the Iberian Peninsula, the South-Eastern European Mainland, and Central Europe, whose origin fits well with a model of species glacial isolation and post-glacial re-expansion from the Mediterranean and extra-Mediterranean refugia during the late Pleistocene. As expected, a fourth biogeographic cluster was identified in the isolated and almost genetically compromised Scotland wildcat population , which showed unique wild and domestic haplotypes. Based on their wild ancestry content, such biogeographic clusters could be used to identify four possible preliminary corresponding Conservation Units (CU, ) to be treated as different management priorities and preserved through well-planned conservation actions, depending on their wild genomic mito-nuclear concordance. Interestingly, our data also show the presence of mtDNA haplotypes shared between wild and domestic cat populations, likely resulting from two different independent evolutionary processes, historical natural gene flow among wild lineages, and recent wild x domestic anthropogenic hybridization. Future studies, based on the analyses of entire mitogenomes and whole nuclear genomes of early domesticated cats from museum collections, modern and ancient European and African wildcats collected also in their overlapping distribution ranges (from Turkey to the Near East), could undoubtedly help researchers to disentangle this complex biogeographic mosaic, clarify the evolutionary histories and admixture patterns, as well as shed light on the origin of the current mito-nuclear variability of the European wildcat populations and their long-term adaptive potential. Acknowledgments We thank all the colleagues who contributed over different years and numerous projects to collect the felid biological samples and who gave invaluable advice and support, in particular: Alvares F., Alves P.C., Bohle R., Bologna M.A., Delogu M., Duperon E., De Faveri A., Fabbri E., Giuliani A., Godinho R., Herrmann M., Hupe K., Knauze D., Lapini L., Liberek M., Lopez Bao J.V., Lucchesi M., Malsana M., Meleon M., Moes M., Mucci N., Oliveira R., Potocnik H., Randi E., Ribeiro A., Romy M.P., Ruiz-Gonzalez A., Sforzi A., Suchentrunk F., Tedaldi G., Vercillo F., Zsolt B. We are also indebted to Selvatici M.A., Cazzato M., Dotti R., and Morreale E. (ISPRA) for their precious support with the administrative practices needed for the publication of the manuscript. We also thank the Academic Editor and two anonymous referees for providing a straightforward revision process and helpful suggestions. We are infinitely grateful to Ragni B., who spent most of his life studying the European wildcat ssp in Italy, collecting a large part of the samples analyzed in this work; thus, we would like to dedicate this paper to his memory. Supplementary Materials The following supporting information can be downloaded at: Results from Phylogenetic and Phylogeographic Analyses; Figure S1: ABC simulated evolutionary scenarios; Figure S2: Neighbor-joining and maximum-likelihood topology trees; Table S1: Sample database; Table S2: NAD5 haplotype sequences; Table S3: NAD5 haplotype frequencies. Click here for additional data file. Author Contributions Conception and planning: E.V., R.C. and F.M.; Genetic analysis: E.V. and F.M.; Statistical analyses: E.V. and F.M.; Writing--Original Draft Preparation: E.V., R.C. and F.M.; Writing--Review and Editing E.V., R.C. and F.M. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Data presented in this study are available on request. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Map of the approximate cat sampling locations. Dark grey areas correspond to the most recently updated IUCN Felis silvestris distribution range . Macro-regions (Italy, Central Europe, Iberian Peninsula, Balkans, Eastern Europe, Scotland) are indicated in different colors. Each macro-region was further subdivided into sub-regions (It-cnt: Central Italy; It-Sicily: Sicily; Eu-cnt: Center-North Germany; Eu-sw: Southern and Western regions of Central Europe; Ib-prt: Portugal; Ib-sp: Spain; Balk-n: Northern Balkans; Balk-s: Southern Balkans; Balk-nw Eastern Italian Alps and North-Western Dinarides; East-n: Poland; East-s: Hungary). Samples from the North-Eastern Italian Alps were included in the Balkans group (blk-nw) according to the most recent genetic structure detected in Europe through Bayesian assignment procedures performed using nuclear microsatellite genetic profiles . Small circles indicate the approximate geographic locations within the main sampling areas. Each sub-region is provided with the number of analyzed samples classified on the base of their 31-STR assignment values : W = wildcat; D = domestic cat; H = putative admixed. Further details are available in Supplementary Table S1. Figure 2 (a) Bayesian mtDNA tree (BT) computed in Beast showing the phylogenetic relationships among ND5 haplotypes obtained from all the 715 analyzed cat samples. Capitalized letters (D, W) indicate the two main lineages. Roman numerals (I-V) in coloured box indicate the main clades. Grey cartoons indicate the estimated node divergence times, whose 95% posterior density confidential intervals are reported in brackets. Annotated nodes show the Bayesian highest posterior density values and also the respective bootstrap values derived from the NJ and ML trees. (b) MJ networks among ND5 haplotypes were obtained from all 715 analyzed cat samples. Haplotypes, according to the 31-STR Bayesian assignment values of their belonging samples , were partitioned and colored as domestic, wild, and putative admixed groups. (c) MJ networks among ND5 haplotypes, including only wildcats and putative admixed individuals (n = 502). Each haplotype was divided and colored according to the proportion of individuals belonging to each biogeographic macro-region. Small bars indicate the number of mutations (greater than one) between two different haplotypes. The frequency of each haplotype is proportional to the size of the circles. Figure 3 Distribution map of the main six haplogroup clades derived from the Bayesian tree. Donut charts show the proportional frequency of haplogroups of lineage W. The inscribed pie charts show the proportional frequency of lineage DW (lineage D pruned by domestic cats). Circles are approximately proportional to sample size. Black solid curved lines trace the geographical separations among genetic clusters detected in both lineages W and DW through SAMOVA analyses, while dotted line shows the additional genetic separation found for lineage W. Black numbers in white circles indicate the clusters found by SAMOVA analyses for lineage W. White numbers in black circles show the clusters found by SAMOVA analyses for lineage DW. Figure 4 Mismatch distribution plots computed using haplogroups showing significant values of Tajima's D and Fu and Li's F indexes. Larger plots show mismatch distribution results about lineage D (considering only domestic cat samples) and lineage W. Smaller plots show mismatch distribution results about different macro-regions within each of the two lineages. Figure 5 Graphical representation of the resulting population sizes and divergence times estimated for the two best-simulated scenarios inferred by ABC simulations, using a generation time g = 2 years. The width of branches is proportional to the inferred effective population sizes. (a) The best scenario was inferred using lineage W haplotypes. (b) The best scenario was inferred using lineage DW (lineage D pruned by domestic cats) haplotypes. Cluster numbers refer to the best K repartition obtained by SAMOVA analyses for each of the two lineages. animals-13-00953-t001_Table 1 Table 1 Summary of genetic variability statistics obtained by analyzing a portion of the mitochondrial ND5 gene and considering as sample groups: (a) STR Bayesian assignment cat populations ; (b) main phylogenetic lineages; and (c) biogeographic macro-regions within each phylogenetic lineage. For lineages W and DW (lineage D pruned by domestic cats), the statistics are also provided for each macro-region. N = number of samples; SD = standard deviation. N Number of Haplotypes Nucleotide Diversity (p +- SD) Haplotype Diversity (h +- SD) Tajima's D p-Value Fu and Li's F p-Value Overall 715 28 0.870 +- 0.013 0.862 +- 0.006 Domestic cats 213 12 0.230 +- 0.150 0.735 +- 0.018 -0.413 0.078 -2.337 0.026 Putative admixed 72 8 0.686 +- 0.378 0.797 +- 0.027 1.145 0.173 4.129 0.442 Wildcats 430 20 1.063 +- 0.552 0.813 +- 0.011 2.297 0.405 4.534 0.280 Lineage D 448 14 0.247 +- 0.161 0.746 +- 0.012 -0.347 0.067 -2.271 0.046 Lineage W 267 14 0.255 +- 0.166 0.720 +- 0.021 -0.452 0.059 -2.789 0.030 Italy 55 4 0.048 +- 0.055 0.173 +- 0.068 -1.025 0.043 -1.780 0.009 Central Europe 117 7 0.165 +- 0.121 0.676 +- 0.034 -0.359 0.098 -0.706 0.103 Iberian Peninsula 40 5 0.245 +- 0.164 0.637 +- 0.063 0.434 0.135 1.091 0.260 Balkans 43 2 0.014 +- 0.028 0.047 +- 0.044 -1.480 0.001 -0.723 0.042 Eastern Europe 8 4 0.230 +- 0.174 0.750 +- 0.139 1.347 0.234 -0.375 0.030 Scotland 7 1 Lineage DW 235 7 0.208 +- 0.142 0.581 +- 0.034 0.415 0.223 0.742 0.202 Italy 54 4 0.207 +- 0.144 0.461 +- 0.058 1.288 0.359 1.942 0.388 Central Europe 41 3 0.037 +- 0.047 0.096 +- 0.062 -2.002 0.000 -1.107 0.047 Iberian Peninsula 8 2 0.064 +- 0.073 0.429 +- 0.169 0.334 0.479 0.536 0.132 Balkans 61 5 0.260 +- 0.170 0.571 +- 0.055 1.461 0.366 1.828 0.341 Eastern Europe 64 4 0.199 +- 0.139 0.656 +- 0.035 1.235 0.384 1.993 0.406 Scotland 7 1 animals-13-00953-t002_Table 2 Table 2 Analysis of molecular variance (AMOVA) on a portion of the mitochondrial ND5 gene computed among and within three different sample groups: (a) the STR Bayesian assignment populations ; (b) the main phylogenetic lineages; and (c) the biogeographic macro-regions within each phylogenetic lineage. phST: differences among groups; phSC: differences among populations within a group. All values were highly significant (p < 0.05). Lineage DW represents lineage D pruned by domestic cats. Source of Variation Variance Components Percentage of Variation Differentiation Indexes Among wildcats, domestic cats, and putative admixed 1.51 36.66 phST = 0.37 Within wildcats, domestic cats, and putative admixed 2.60 63.34 Among lineages W/DW 5.68 86.68 phST = 0.92 Among macro-regions/within lineages 0.37 5.60 phSC = 0.42 Within macro-regions 0.51 7.72 Lineage W Among macro-regions 0.59 58.24 phST = 0.58 Within macro-regions 0.42 41.76 Lineage DW Among macro-regions 0.12 17.21 phST = 0.17 Within macro-regions 0.60 82.79 Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000228 | Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs. RNU UTUC transitional cell carcinoma treatment outcomes surgical approach This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. pmc1. Introduction Urothelial cancers are the sixth most common tumors in developed countries, of which upper tract urothelial cancers (UTUC) account for only 5-10% . Indeed, UTUC is a rare disease with a worse prognosis when compared to similarly staged bladder cancer . Treatment of high-risk, non-metastatic UTUC is mainly based on radical nephroureterectomy (RNU) with bladder cuff excision (BCE), with or without lymph node dissection (LND) . The growth of minimally invasive techniques for RNU has significantly changed the surgical treatment landscape of UTUC. The use of laparoscopic (LRNU) and robotic (RRNU) RNU increased from 36% to 54% between 2004 and 2013 . However, survival and perioperative outcomes of LRNU and RRNU (compared to ORNU) have been mostly assessed in small-cohort studies or from national databases with associated weaknesses in design. Therefore, the current evidence on the survival and perioperative outcomes remains weak, and the available studies show large heterogeneity in statistical approaches. Thus, the present work aimed to provide more robust data on the three different surgical approaches (ORNU, LRNU, and RRNU) and present their impact on survival and perioperative outcomes in patients with high-risk non-metastatic UTUC. 2. Materials and Methods 2.1. Cohort Description and Patient Management This was a retrospective, multicenter study involving 21 academic centers from Europe, Asia, and the United States. Patients' medical records were retrospectively screened to identify individuals with high-risk UTUC treated with open, laparoscopic, or robotic RNU with BCE between 1990 and 2020. Exclusion criteria were clinical metastatic disease (cM+ or cN+) at the time of surgery, history of prior cystectomy due to bladder cancer, and missing follow-up. A predefined data set was used to collect patient information from the medical records of each center, and data were anonymized prior to sharing. The study was approved by the local ethics committees of all participating institutions (protocol code 1566/2017). All RNU procedures were performed using standard techniques with BCE in all included patients. The decision to perform open, laparoscopic, or robot-assisted RNU, as well as a lymphadenectomy and its extent, was at the surgeon's discretion and was performed according to the standard templates described previously . Pathologic examinations of the surgical specimens were performed by genitourinary pathologists at each participating center. Tumor stage was evaluated using the 2002 Union for International Cancer Control's Tumor, Node, Metastasis Classification System. Tumor grade was assessed by the World Health Organization classification of 2004/2016. For cases before 2002 and 2004, a pathological review with restaging and regrading was performed. 2.2. Follow-Up and Outcome Measurement The primary objective of this study was to assess the impact of the surgical approach on survival outcomes, specifically with recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) as the primary endpoints. Recurrence was defined as any local or distant recurrence/metastasis after RNU, and RFS was defined as the time interval between RNU and the first detection of recurrence. Bladder recurrence was considered separately, and BRFS was defined as the time interval between the date of RNU and first detection of bladder recurrence at follow-up cystoscopy. CSS was defined as the time interval between the date of RNU and disease-related death. OS was defined as the time interval between the time of RNU and death of any cause. The schedule for follow-up was based on international recommendations at the time of treatment and on the physicians' preference. In general, surveillance included cross-sectional imaging and cystoscopy every three months for the first two years, semiannually from the second to the fifth year, and then annually. Cause of death was determined by the treating physicians and confirmed by a chart review and/or death certificates . The secondary objective was to evaluate the association of the surgical approach with perioperative characteristics. Secondary endpoints included intraoperative blood loss, hospital length of stay, overall complications within 30 days postoperative (Clavien-Dindo classification 1-5), and major postoperative complications (MPCs) within 30 days postoperative (Clavien-Dindo classification >= 3). 2.3. Statistical Analysis To assess the differences between categorical variables, Pearson's chi-squared or Fisher's exact test were used, and for continuous or ordinal variables, the Kruskal-Wallis rank-sum test was used. Missing data (Supplementary Table S1) were assumed to be missing at random and were replaced with a multiple imputation of chained equations by using 15 data sets to minimize the simulation error (Monte Carlo) . For the imputation of numerical data, predictive mean matching was used, and for binary data, logistic regression imputation was used. For categorical data, polytomous logistic regressions (factor data with unordered levels >2) or classification and regression trees (factor data with ordered levels >2) were performed. Strip plots were generated depicting the discrepancy between the observed and imputed data for verifying the plausibility of imputations . Next, a 1:1:1 propensity score matching (PSM) analysis was performed to reduce selection bias and adjust for the effects of unbalanced covariates. Adjusting variables were chosen which influence survival outcomes but do not relate to the exposure (surgical procedure) in order to increase the precision of the estimated exposure effect without increasing bias . The balance of covariates before and after propensity score matching was assessed by visual inspection using love plots to indicate mean differences . Kaplan-Meier curves were used to estimate survival outcomes, and pairwise log-rank tests were utilized to compare these between the three different surgical approaches. Univariable and multivariable Cox regression analyses were performed to examine the association between surgical approaches and survival outcomes. Univariable and multivariable linear and logistic regression analyses were performed to examine the association between surgical approaches and perioperative outcomes. In the multivariable analysis, all variables were included, which demonstrated a statistically significant association with the corresponding dependent variable in the univariable analysis. Statistical significance was set at p < 0.05. All tests were two-sided. All statistical analyses were performed using R (version 4.0.3, Vienna, Austria, 2020). 3. Results 3.1. Study Cohort and Clinicopathologic Characteristics A total of 2434 patients met our inclusion criteria. The median percentage of missing data for the variables was 11% (IQR 6.25, 23.1) (Supplementary Table S1). After PSM, we obtained a cohort of 756 patients, with 252 patients in each intervention group (ORNU, LRNU, and RRNU). Table 1 provides an overview of the clinicopathologic characteristics of the initial study population, the study population after multiple imputation, and the study population after propensity score matching. The PSM cohort's median age was 72 years (IQR 64, 78), and 251 (33%) patients were female. Clinical and pathological demographics were similar among the three different surgical approaches, except for a significant difference between the years of surgery performed (p < 0.001), with an increasing use of LRNU from 2000-2005 and RRNU from 2006-2010. Among the perioperative characteristics, RRNU presented less intraoperative blood loss (100 mL (IQR 60, 200) vs. 150mL (IQR 75, 250) in LRNU vs. 200 mL (IQR 50, 350) in ORNU; p < 0.001), a shorter inpatient stay (4 days (IQR 2, 6) vs. 8 days (IQR 5, 14) after LRNU vs. 10 days (IQR 6, 15) after ORNU; p < 0.001), fewer overall postoperative complications (25.4% vs. 36.1% in LRNU vs. 39.1% in ORNU; p = 0.02), and fewer major postoperative complications (7.9% vs. 16.7% in LRNU vs. 20.2% in ORNU; p < 0.001). 3.2. Association of the Surgical Approach with Survival Outcomes During a median follow-up among the PSM cohort of 32 months (IQR 15, 61), 191 patients experienced disease recurrence, 292 developed bladder recurrence, 111 patients died of disease, and 86 patients died from other causes. The 3-year estimates for RFS, BRFS, CSS, and OS, as well as the associated Kaplan-Meier curves and pairwise log-rank tests, are provided in Figure 1A-D. While there was no difference in the pairwise log-rank tests for the 3-year RFS, CSS, and OS between the three surgical approaches, improved BRFS was observed for ORNU (3-year BRFS: 73.5% (67.7-79.8)) compared to LRNU (3-year BRFS: 58.8% (52.5-65.8); pairwise log-rank: p < 0.001) and RRNU (3-year BRFS: 58.9% (51.9-66.7); pairwise log-rank: p < 0.001). Variables associated with RFS, BRFS, CSS, and OS are shown in Table 2. In the multivariable Cox regression analyses adjusted for possible confounders which were significantly associated with the according survival outcome in univariable regression analyses, both laparoscopic approaches (LRNU and RRNU) were independently associated with worse BRFS (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.22-2.28, p = 0.001 and HR 1.73, CI 1.22-2.47, p = 0.002, respectively). In the univariable and multivariable Cox regression analyses assessing the associations with RFS, CSS, and OS, the surgical approach was not shown to be associated with RFS, CSS, or OS in either the univariable or multivariable analyses. 3.3. Association of the Surgical Approach with Perioperative Outcomes Table 3 provides the associations of variables with perioperative outcomes. On multivariable regression analyses adjusted for possible confounders which were significantly associated with the according perioperative outcome in univariable regression analyses, the RRNU approach was independently associated with a shorter hospital stay (beta -6.1, CI -7.2-5.0; p < 0.001), fewer overall postoperative complications (odds ratio (OR) 0.53, CI 0.36-0.78; p = 0.001) and fewer MPCs (OR 0.27, CI 0.16-0.46; p < 0.001). Similarly, LRNU was independent associated with a shorter hospital stay (beta -1.1, CI -2.3-0.02; p = 0.047) and fewer MPCs (OR 0.50, CI 0.31-0.79; p = 0.003). There were no significant associations in the multivariable regression analyses between surgical approaches and intraoperative blood loss. 4. Discussion In the present study, we investigated the association of the surgical RNU approach with the survival and perioperative outcomes in a large, propensity-score-matched cohort of patients suffering from non-metastatic UTUC treated with either ORNU, LRNU, or RRNU. We found no differences in terms of RFS, CSS, and OS between the three approaches. In contrast, we identified minimally invasive procedures (LRNU and RRNU) as independent predictors of worse BRFS. Moreover, we found an independent association between the RRNU approach with a shorter hospital length of stay and lower rates of overall and major complications. Several previous studies investigated the impact of the surgical RNU approach on survival outcomes . Most of these retrospective studies reported similar outcomes in terms of progression-free survival (PFS), CSS, and OS between the three different surgical approaches despite their different statistical approaches, methods, and cohort sizes . The most recent meta-analysis by Vecchia et al., which investigated the effect of the surgical technique (ORNU, LRNU, or RRNU) on PFS and CSS in approximately 87,000 patients, observed no significant difference . Thus far, the only prospective study in the current literature that has investigated whether ORNU or LRNU has an impact on survival outcomes reported no differences in PFS and CSS between the two procedures . Overall, these homogeneous results from different studies are consistent with the findings in our study, and thus strengthen the previous evidence that the choice of surgical method does not seem to affect RFS/PFS, CSS, and OS. However, it should be noted that these survival measures contain mainly estimated 5-year survival data, and there is only little evidence on long-term survival outcomes after LRNU and RRNU. In the present study, we found a significant and independent association between LRNU and RRNU with a worse BRFS compared to ORNU. According to the current literature, BRFS as an endpoint related to the different surgical approaches has been investigated in only a few studies thus far, and the results are conflicting . Simone et al., who conducted the first and only small-scale prospective study comparing survival outcomes between LRNU and ORNU, found no differences in BRFS between the two approaches . Similar results were reported by Clements et al. in 2018, who found no difference among ORNU, LRNU, or RRNU in 3801 UTUC patients . In contrast, in a propensity-score-matched cohort of 1276 patients, Kim et al. 2019 demonstrated that LRNU has a favorable effect on BRFS . In the current literature, there are studies that identified predictors of worse BRFS and whose results partially support our findings . Xylinas et al. showed, in an extensive series of North American UTUC patients, that the laparoscopic surgical technique and endoscopic management of the distal ureter were independent predictors of worse BRFS, which was successfully validated in a European cohort . Shigeta et al. found that LRNU with a pneumoperitoneum time >150min was a strong, independent predictor of worse BRFS . In a series of ORNU, it was demonstrated that distal ureteral clipping prior to mobilization of the kidney and ureter has a positive impact on BRFS . Pizzighella et al. identified distal ureteral tumor localization as a risk factor for worse BRFS . Furthermore, BCE techniques used with open or laparoscopic approaches and their impact on BRFS have been investigated in a few small studies, with heterogenous results being obtained thus far . Therefore, the causes of bladder recurrence after RNU might be manifold, including not only the surgical approach but also the influence of the surgical technique with regard to distal ureteral management, surgery duration, and tumor location. Whether the surgeon's experience and dexterity, which may play a role in laparoscopic approaches, has an influence, has not been yet investigated. The fact that only about one-eighth of patients in the present study received perioperative intravesical chemotherapy further supports the previous recommendation that such a therapy should be performed, as it may improve BRFS, especially for minimally invasive approaches . In direct comparison, our PSM cohort showed increasingly better and significantly different perioperative parameters from ORNU to LRNU and to RRNU. Blood loss, the number and severity of postoperative complications, and the hospital length of stay were all better in the RRNU group, followed by LNRU, and worst after ORNU. In the multivariable regression analysis, we found a significant benefit for RRNU and LRNU compared to ORNU. Our findings regarding complications and hospital length of stay are consistent with previous larger-scale studies which performed a similar robust statistical analysis . However, the three surgical techniques had few major complications and, given the similar survival outcomes, all approaches can be considered as feasible treatment options for patients suffering from non-metastatic UTUC. Our study is not free of limitations. First, its retrospective and multicenter nature is characterized by the lack of strictly standardized protocols for patient selection and postoperative follow-up, which implies selection bias. Moreover, it should be noted that different surgeons with different surgical techniques and experiences may influence the present results. For example, we only had precise information on the BCE technique and if a ureter clipping was performed in a minority of patients; therefore, this could not have been augmented by multiple imputation. Furthermore, the retrospective setting means that patients are usually followed up by general practitioners after an average follow-up period of 2-3 years, which resulted in shorter survival data available to us. Future studies are required to assess the impact of BRFS on long-term survival as well on patient's quality of life. Despite the fact that the present data come from several developed countries from all over the world with well-equipped and medically trained centers, it must be noted that the results of this study probably cannot be generalized to developing countries. However, this is the first large-scale study comparing survival and perioperative outcomes between ORNU, LRNU, and RRNU, whereby detailed information on patient, preoperative, perioperative, postoperative, surgical, and pathological characteristics are available. Moreover, we were able to impute missing variables using a statistically powerful method which uses prediction models to create multiple data sets, and thus could impute meaningful values compared to other imputation methods, reducing the sizes of the standard errors at the same time. 5. Conclusions In the present study, we confirmed previous findings that ORNU, LRNU, and RRNU have comparable RFS, CSS, and OS. Moreover, minimal invasive procedures (LRNU and RRNU) were shown to have a significantly worse BRFS. In order to identify the associated factors that promote bladder recurrence, additional studies are warranted to further improve the minimal invasive techniques in the future. In terms of perioperative outcomes, LRNU and RRNU were independently associated with shorter hospital length of stay and fewer major complications. However, all surgical procedures appear to be generally safe treatment options. Acknowledgments Nico C. Grossmann is supported by the Zurich Cancer League. Pawel Rajwa and Ekaterina Laukhtina are supported by the EUSP Scholarship of the European Association of Urology (EAU). Supplementary Materials The following supporting information can be downloaded at: Table S1: Overview of the number of missing and imputed variables of the initial data set; Figure S1: Strip plots depicting the discrepancy between the observed and imputed data, specifying a maximum number of iterations of 50 and the number of imputation data sets of 15. The blue dots represent the original data and the red dots the imputed data; Figure S2: Love plot indicating the balance before and after propensity score matching across all 15 imputations. Click here for additional data file. Author Contributions Conceptualization, N.C.G., S.F.S. and B.P.; data curation, N.C.G., F.S., T.J., A.M.P., H.D., A.G., E.K., A.M., Z.-E.K., K.F., J.D.R., A.B., M.F., J.P.S., J.L.P., E.L., P.R., M.P., C.P., G.E.C., T.v.D., J.L.B., A.A., M.J., F.A., G.P., A.H., E.S., S.D., S.A.B., M.R. (Morgan Roupret), M.R. (Michael Rink), S.F.S. and B.P.; formal analysis, N.C.G. and B.P.; investigation, N.C.G. and B.P.; methodology, N.C.G., S.F.S. and B.P.; project administration, B.P. and S.F.S.; supervision, G.P., A.H., S.D., S.A.B., M.R. (Morgan Roupret), M.R. (Michael Rink), S.F.S. and B.P.; validation, F.S., T.J., A.M.P., H.D., A.G., E.K., A.M., Z.-E.K., K.F., J.D.R., A.B., M.F., J.P.S., J.L.P., E.L., P.R., M.P., C.P., G.E.C., T.v.D., J.L.B., A.A., M.J., F.A., G.P., A.H., E.S., S.D., S.A.B., M.R. (Morgan Roupret), M.R. (Michael Rink), S.F.S. and B.P.; visualization, N.C.G.; writing--original draft, N.C.G. and B.P.; writing--review and editing, F.S., T.J., A.M.P., H.D., A.G., E.K., A.M., Z.-E.K., K.F., J.D.R., A.B., M.F., J.P.S., J.L.P., E.L., P.R., M.P., C.P., G.E.C., T.v.D., J.L.B., A.A., M.J., F.A., G.P., A.H., E.S., S.D., S.A.B., M.R. (Morgan Roupret), M.R. (Michael Rink) and S.F.S. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board (or Ethics Committee) of each contributing institution (protocol code 1566/2017). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement The data presented in this study are available upon request from the corresponding author. The data are not publicly available due to privacy restrictions. Conflicts of Interest All authors have no conflict of interest to disclose. Figure 1 Kaplan-Meier analysis and log-rank tests for recurrence-free survival (A), bladder recurrence-free survival (B), cancer-specific survival (C), and overall survival (D) of a multiple-imputed and propensity-score-matched cohort of 756 patients treated with radical nephroureterectomy for UTUC stratified by the surgical approach. cancers-15-01409-t001_Table 1 Table 1 Baseline, peri-, and postoperative characteristics of patients with UTUC stratified by the type of surgical RNU approach in the original cohort, in the cohort after multiple imputation, and in the cohort after multiple imputation and propensity score matching. Original Cohort Multiple-Imputed Cohort Multiple-Imputed and Propensity-Score-Matched Cohort Total Cohort Surgical Approach Total Cohort Surgical Approach Total Cohort Surgical Approach Characteristic N = 2434 Open RNU, N = 1096 Laparoscopic RNU, N = 865 Robotic RNU, N = 473 p-Value N = 2434 Open RNU, N = 1096 Laparoscopic RNU, N = 865 Robotic RNU, N = 473 p-Value N = 756 Open RNU, N = 252 Laparoscopic RNU, N = 252 Robotic RNU, N = 252 p-Value Age 71 (64, 77) 70 (63, 77) 72 (65, 78) 71 (63, 77) <0.001 71 (64, 77) 70 (63, 77) 72 (65, 78) 71 (63, 77) <0.001 72 (64, 78) 73 (66, 78) 72 (65, 78) 70 (62, 77) 0.05 Missing 4 3 1 0 Female Gender 780 (32%) 326 (30%) 264 (31%) 190 (40%) <0.001 781 (32%) 327 (30%) 264 (31%) 190 (40%) <0.001 251 (33%) 85 (34%) 82 (33%) 84 (33%) >0.9 Missing 3 3 0 0 ASA <0.001 <0.001 0.5 1 129 (6.8%) 30 (4.0%) 62 (9.0%) 37 (8.0%) 172 (7.1%) 50 (4.6%) 85 (9.8%) 37 (7.8%) 45 (6.0%) 10 (4.0%) 14 (5.6%) 21 (8.3%) 2 863 (46%) 372 (50%) 292 (42%) 199 (43%) 1081 (44%) 534 (49%) 341 (39%) 206 (44%) 339 (45%) 116 (46%) 115 (46%) 108 (43%) 3 855 (45%) 323 (44%) 325 (47%) 207 (45%) 1107 (45%) 480 (44%) 418 (48%) 209 (44%) 346 (46%) 115 (46%) 115 (46%) 116 (46%) 4 48 (2.5%) 17 (2.3%) 10 (1.5%) 21 (4.5%) 74 (3.0%) 32 (2.9%) 21 (2.4%) 21 (4.4%) 26 (3.4%) 11 (4.4%) 8 (3.2%) 7 (2.8%) Missing 539 354 176 9 BMI 25.8 (23.0, 28.9) 25.4 (22.6, 28.7) 25.7 (23.0, 28.6) 26.2 (23.8, 29.6) <0.001 25.8 (23.0, 29.0) 25.6 (22.5, 29.0) 25.7 (22.9, 28.8) 26.2 (23.8, 29.6) 0.001 26 (23, 29) 25.6 (22.3, 28.9) 26.0 (23.0, 29.0) 26.0 (23.4, 29.0) 0.3 Missing 585 377 201 7 Previous bladder cancer 649 (29%) 284 (32%) 253 (30%) 112 (24%) 0.009 720 (30%) 342 (31%) 266 (31%) 112 (24%) 0.007 216 (29%) 75 (30%) 77 (31%) 64 (25%) 0.4 Missing 233 200 29 4 Hydronephrosis 846 (43%) 336 (42%) 300 (43%) 210 (45%) 0.5 1044 (43%) 447 (41%) 384 (44%) 213 (45%) 0.2 316 (42%) 91 (36%) 111 (44%) 114 (45%) 0.08 Missing 462 290 163 9 Tumor location <0.001 <0.001 0.5 Pelvicaliceal 1360 (64%) 617 (67%) 451 (62%) 292 (63%) 1611 (66%) 757 (69%) 558 (65%) 296 (63%) 487 (64%) 160 (63%) 163 (65%) 164 (65%) Ureter 683 (32%) 281 (30%) 257 (36%) 145 (31%) 746 (31%) 308 (28%) 290 (34%) 148 (31%) 244 (32%) 80 (32%) 81 (32%) 83 (33%) Both 66 (3.1%) 25 (2.7%) 14 (1.9%) 27 (5.8%) 77 (3.2%) 31 (2.8%) 17 (2.0%) 29 (6.1%) 25 (3.3%) 12 (4.8%) 8 (3.2%) 5 (2.0%) Missing 325 173 143 9 Diagnostic ureteroscopy performed 1376 (67%) 570 (70%) 528 (66%) 278 (66%) 0.1 1656 (68%) 602 (70%) 743 (68%) 311 (66%) 0.3 507 (67%) 172 (68%) 165 (65%) 170 (67%) 0.8 Missing 391 52 290 49 Neoadjuvant chemotherapy 122 (5.0%) 77 (7.0%) 27 (3.1%) 18 (3.8%) <0.001 122 (5.0%) 77 (7.0%) 27 (3.1%) 18 (3.8%) <0.001 18 (2.4%) 6 (2.4%) 6 (2.4%) 6 (2.4%) >0.9 Missing 1 1 0 0 Year of surgery <0.001 <0.001 <0.001 1990-1999 129 (5.7%) 128 (14%) 1 (0.1%) 0 146 (6.0%) 145 (13%) 1 (0.1%) 0 27 (3.6%) 27 (11%) 0 (0%) 0 (0%) 2000-2005 222 (9.8%) 127 (13%) 95 (11%) 0 238 (9.8%) 137 (12%) 101 (12%) 0 49 (6.5%) 22 (8.7%) 27 (11%) 0 (0%) 2006-2010 424 (19%) 232 (25%) 184 (22%) 8 (1.7%) 480 (20%) 285 (26%) 187 (22%) 8 (1.7%) 129 (17%) 73 (29%) 50 (20%) 6 (2.4%) 2011-2015 744 (33%) 277 (29%) 295 (35%) 172 (36%) 789 (32%) 320 (29%) 297 (34%) 172 (36%) 264 (35%) 81 (32%) 90 (36%) 93 (37%) 2016-2020 737 (33%) 179 (19%) 265 (32%) 293 (62%) 781 (32%) 209 (19%) 279 (32%) 293 (62%) 287 (38%) 49 (19%) 85 (34%) 153 (61%) Missing 178 153 25 0 Side of surgery 0.2 0.3 0.2 Left 1105 (50%) 483 (51%) 414 (49%) 208 (46%) 1199 (49%) 556 (51%) 423 (49%) 220 (47%) 367 (49%) 123 (49%) 132 (52%) 112 (44%) Right 1125 (50%) 459 (49%) 426 (51%) 240 (54%) 1235 (51%) 540 (49%) 442 (51%) 253 (53%) 389 (51%) 129 (51%) 120 (48%) 140 (56%) Missing 204 154 25 25 Lymphadenectomy performed 851 (37%) 412 (41%) 245 (30%) 194 (43%) <0.001 903 (37%) 444 (41%) 256 (30%) 203 (43%) <0.001 260 (34%) 86 (34%) 78 (31%) 96 (38%) 0.2 Missing 154 86 47 21 Blood loss (mL) 200 (100, 350) 300 (200, 500) 192 (100, 300) 100 (70, 200) <0.001 200 (90, 250) 200 (100, 400) 150 (75, 250) 100 (60, 200) <0.001 150 (75, 250) 200 (150, 350) 150 (751, 250) 100 (60, 200) <0.001 Missing 895 498 361 36 Surgery duration (min) 250.00 (190.25, 324.00) 245 (187, 320) 264 (210, 343) 240 (180, 310) <0.001 200 (196, 312) 200 (196, 305) 200 (196, 319) 240 (181, 312) 0.006 201 (196, 310) 200 (196, 305) 208 (196, 319) 240 (182, 308) 0.4 Missing 1232 666 487 79 Perioperative intravesical chemotherapy Instillation 240 (14%) 73 (11%) 112 (20%) 55 (13%) <0.001 394 (16%) 149 (14%) 183 (21%) 62 (13%) <0.001 100 (13%) 32 (13%) 30 (12%) 38 (15%) 0.5 Missing 762 408 306 48 Pathological tumor stage 0.007 0.007 0.8 <=pT1 1251 (51%) 525 (48%) 484 (56%) 242 (51%) 1251 (51%) 525 (48%) 484 (56%) 242 (51%) 411 (54%) 134 (53%) 144 (57%) 133 (53%) pT2 365 (15%) 172 (16%) 114 (13%) 79 (17%) 365 (15%) 172 (16%) 114 (13%) 79 (17%) 109 (14%) 39 (15%) 32 (13%) 38 (15%) pT3/pT4 818 (34%) 399 (36%) 267 (31%) 152 (32%) 818 (34%) 399 (36%) 267 (31%) 152 (32%) 236 (31%) 79 (31%) 76 (30%) 81 (32%) Pathological tumor grade 0.02 0.06 0.6 Low grade 571 (24%) 243 (23%) 228 (28%) 100 (21%) 599 (25%) 259 (24%) 236 (27%) 104 (22%) 187 (25%) 57 (23%) 64 (25%) 66 (26%) High grade 1784 (76%) 817 (77%) 600 (72%) 367 (79%) 1835 (75%) 837 (76%) 629 (73%) 369 (78%) 569 (75%) 195 (77%) 188 (75%) 186 (74%) Missing 79 36 37 6 Tumor multifocality 603 (26%) 295 (28%) 207 (24%) 101 (23%) 0.06 624 (26%) 304 (28%) 211 (24%) 109 (23%) 0.09 177 (23%) 57 (23%) 61 (24%) 59 (23%) >0.9 Missing 82 42 10 30 Number of lymph nodes removed 6.00 (3.00, 13.00) 6 (3, 12) 6 (2, 12) 8 (3, 14) 0.047 6 (3, 13) 6 (3, 12) 6 (2, 12) 8 (3, 14) 0.047 7 (3, 12) 6 (4, 11) 7 (3, 12) 7 (2, 14) 0.7 Missing 170 88 62 20 Lymph node involvement 264 (11%) 147 (13%) 68 (7.9%) 49 (10%) <0.001 264 (11%) 147 (13%) 68 (7.9%) 49 (10%) <0.001 59 (7.8%) 16 (6.3%) 21 (8.3%) 22 (8.7%) 0.8 Lymphovascular invasion 399 (16%) 177 (16%) 136 (16%) 86 (18%) 0.5 400 (16%) 178 (16%) 136 (16%) 86 (18%) 0.5 124 (16%) 41 (16%) 38 (15%) 45 (18%) 0.7 Missing 1 1 0 0 Concomitant carcinoma in situ 388 (16%) 170 (16%) 141 (16%) 77 (16%) 0.9 388 (16%) 170 (16%) 141 (16%) 77 (16%) 0.9 116 (15%) 37 (15%) 40 (16%) 39 (15%) >0.9 Positive soft tissue surgical margins 75 (3.9%) 37 (5.1%) 24 (3.4%) 14 (3.0%) 0.1 109 (4.5%) 66 (6.0%) 29 (3.4%) 14 (3.0%) 0.004 31 (4.1%) 16 (6.3%) 9 (3.6%) 6 (2.4%) 0.07 Missing 534 368 163 3 Variant histology 110 (5.1%) 38 (4.2%) 30 (3.7%) 42 (9.5%) <0.001 135 (5.5%) 54 (4.9%) 35 (4.0%) 46 (9.7%) <0.001 39 (5.2%) 13 (5.2%) 12 (4.8%) 14 (5.6%) >0.9 Missing 267 186 50 31 Highest complication (Clavien-Dindo classification) 0.1 <0.001 0.02 No complications 1345 (73%) 498 (72%) 510 (72%) 337 (78%) 1633 (67%) 703 (64%) 570 (66%) 360 (76%) 504 (67%) 153 (61%) 162 (64%) 189 (75%) 1 112 (6.1%) 38 (5.5%) 55 (7.8%) 19 (4.4%) 132 (5.4%) 50 (4.6%) 63 (7.3%) 19 (4.0%) 39 (5.2%) 12 (4.8%) 16 (6.3%) 11 (4.4%) 2 247 (13%) 98 (14%) 95 (13%) 54 (12%) 311 (13%) 139 (13%) 111 (13%) 61 (13%) 100 (13%) 36 (14%) 32 (13%) 32 (13%) 3a 25 (1.4%) 11 (1.6%) 7 (1.0%) 7 (1.6%) 70 (2.9%) 28 (2.6%) 34 (3.9%) 8 (1.7%) 25 (3.3%) 8 (3.2%) 10 (4.0%) 7 (2.8%) 3b 50 (2.7%) 19 (2.7%) 21 (3.0%) 10 (2.3%) 115 (4.7%) 62 (5.7%) 40 (4.6%) 13 (2.7%) 35 (4.6%) 13 (5.2%) 14 (5.6%) 8 (3.2%) 4a 33 (1.8%) 21 (3.0%) 9 (1.3%) 3 (0.7%) 109 (4.5%) 75 (6.8%) 27 (3.1%) 7 (1.5%) 32 (4.2%) 17 (6.7%) 11 (4.4%) 4 (1.6%) 4b 7 (0.4%) 2 (0.3%) 4 (0.6%) 1 (0.2%) 36 (1.5%) 23 (2.1%) 11 (1.3%) 2 (0.4%) 12 (1.6%) 8 (3.2%) 4 (1.6%) 0 (0%) 5 17 (0.9%) 8 (1.2%) 7 (1.0%) 2 (0.5%) 28 (1.2%) 16 (1.5%) 9 (1.0%) 3 (0.6%) 9 (1.2%) 5 (2%) 3 (1.2%) 1 (0.4%) Missing 598 401 157 40 Number of patients with major complications (Clavien-Dindo classification >=3) 132 (7.0%) 61 (8.5%) 48 (6.6%) 23 (5.1%) 0.08 358 (14.7%) 204 (18.6%) 121 (14%) 33 (7%) <0.001 113 (44.8%) 51 (20.2%) 42 (16.7%) 20 (7.9%) <0.001 Missing 540 375 143 22 Hospital length of stay (days) 7 (4, 10) 9 (6, 12) 7 (4, 12) 4 (3, 5) <0.001 8 (4, 13) 10 (7, 14) 7 (4, 13) 4 (3, 6) <0.001 7 (4, 13) 10 (6, 15) 8 (5, 14) 4 (2, 6) <0.001 Missing 789 489 272 28 Adjuvant chemotherapy 346 (14%) 160 (15%) 127 (15%) 59 (12%) 0.5 346 (14%) 160 (15%) 127 (15%) 59 (12%) 0.5 100 (13%) 34 (13%) 37 (15%) 29 (12%) 0.6 Missing 3 3 0 0 Adjuvant RT 44 (2.4%) 24 (3.2%) 13 (1.8%) 7 (2.0%) 0.2 88 (3.6%) 44 (4.0%) 21 (2.4%) 23 (4.9%) 0.05 34 (4.5%) 12 (4.8%) 6 (2.4%) 16 (6.3%) 0.1 Missing 588 341 123 124 Median (IQR); n (%), Kruskal-Wallis rank-sum test; Pearson's chi-squared test; Fisher's exact test. cancers-15-01409-t002_Table 2 Table 2 multivariable Cox regression analyses assessing the association of the three different surgical approaches with recurrence-free survival, bladder-recurrence-free survival, cancer-specific survival, and overall survival in a multiple-imputed and propensity-score-matched cohort of 756 patients treated with radical nephroureterectomy for UTUC. Recurrence-Free Survival Bladder-Recurrence-Free Survival Cancer-Specific Survival Overall Survival Univariable Multivariable Univariable Multivariable Univariable Multivariable Univariable Multivariable Characteristic HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value HR 95% CI p-Value Surgical approach (reference: open RNU) Laparoscopic RNU 0.93 0.67, 1.31 0.7 0.98 0.70, 1.39 >0.9 1.81 1.35, 2.42 <0.001 1.66 1.22, 2.28 0.001 0.91 0.60, 1.39 0.7 0.92 0.59, 1.41 0.7 0.88 0.64, 1.21 0.4 0.93 0.68, 1.28 0.6 Robotic RNU 1.07 0.75, 1.53 0.7 1.03 0.71, 1.49 0.9 2.05 1.51, 2.77 <0.001 1.73 1.22, 2.47 0.002 0.79 0.48, 1.31 0.4 0.65 0.39, 1.10 0.1 0.83 0.56, 1.22 0.3 0.81 0.55, 1.19 0.3 Age 1.01 1.00, 1.03 0.1 1.00 0.99, 1.01 0.7 1.01 0.99, 1.03 0.2 1.03 1.01, 1.05 <0.001 1.03 1.01, 1.04 0.002 ASA (reference: 1) 2 1.00 0.52, 1.94 >0.9 1.52 0.84, 2.74 0.2 1.54 0.85, 2.80 0.2 0.64 0.32, 1.32 0.2 0.69 0.39, 1.22 0.2 3 1.30 0.68, 2.50 0.4 1.50 0.83, 2.72 0.2 1.36 0.74, 2.50 0.3 0.86 0.42, 1.75 0.7 1.07 0.61, 1.88 0.8 4 1.73 0.70, 4.26 0.2 2.70 1.26, 5.77 0.01 1.88 0.84, 4.20 0.1 1.00 0.31, 3.26 >0.9 1.01 0.39, 2.63 >0.9 BMI 0.99 0.96, 1.01 0.4 1.03 1.01, 1.05 0.006 1.02 0.99, 1.04 0.1 0.97 0.94, 1.01 0.2 0.98 0.95, 1.01 0.2 Gender (reference: male) Female 1.08 0.80, 1.46 0.6 0.85 0.66, 1.09 0.2 1.00 0.68, 1.49 >0.9 1.03 0.77, 1.39 0.8 Previous bladder cancer 1.18 0.87, 1.61 0.3 1.16 0.90, 1.49 0.2 1.21 0.81, 1.81 0.4 1.40 1.04, 1.88 0.03 1.56 1.15, 2.12 0.004 Hydronephrosis 1.22 0.92, 1.63 0.2 1.08 0.86, 1.37 0.5 1.44 0.99, 2.10 0.06 1.15 0.87, 1.54 0.3 Tumor location (reference: pelvicaliceal) Ureter 1.03 0.76, 1.40 0.9 0.86 0.67, 1.10 0.2 1.02 0.68, 1.52 >0.9 0.82 0.60, 1.12 0.2 Both 0.71 0.31, 1.62 0.4 0.48 0.23, 1.02 0.06 1.00 0.40, 2.47 >0.9 0.65 0.30, 1.39 0.3 Diagnostic ureteroscopy performed 1.05 0.77, 1.42 0.8 1.34 1.03, 1.74 0.03 1.35 1.03, 1.78 0.03 1.02 0.68, 1.52 >0.9 0.99 0.73, 1.34 >0.9 Neoadjuvant chemotherapy 3.83 2.01, 7.27 <0.001 3.14 1.56, 6.29 0.001 0.64 0.24, 1.72 0.4 3.47 1.41, 8.57 0.007 2.28 0.89, 5.85 0.09 2.64 1.16, 5.97 0.02 1.62 0.69, 3.79 0.3 Year of surgery (reference: 1990-1999) 2000-2005 1.40 0.62, 3.14 0.4 1.54 0.72, 3.27 0.3 0.95 0.43, 2.10 0.9 1.54 0.60, 3.93 0.4 1.10 0.58, 2.09 0.8 2006-2010 1.12 0.53, 2.35 0.8 1.13 0.57, 2.24 0.7 0.86 0.42, 1.75 0.7 0.85 0.35, 2.09 0.7 0.66 0.36, 1.20 0.2 2011-2015 1.20 0.58, 2.48 0.6 1.31 0.68, 2.55 0.4 0.90 0.44, 1.84 0.8 0.86 0.36, 2.05 0.7 0.76 0.43, 1.36 0.4 2016-2020 1.41 0.67, 2.96 0.4 2.82 1.45, 5.48 0.002 1.72 0.83, 3.59 0.2 1.06 0.43, 2.66 0.9 1.12 0.60, 2.09 0.7 Perioperative intravesical chemotherapy instillation 1.17 0.77, 1.77 0.5 1.53 1.12, 2.10 0.008 1.51 1.08, 2.10 0.02 0.65 0.31, 1.33 0.2 0.80 0.48, 1.31 0.4 Lymphadenectomy performed 1.32 0.98, 1.78 0.07 1.29 0.96, 1.74 0.09 1.66 1.13, 2.42 0.009 1.87 0.73, 4.79 0.2 1.27 0.94, 1.72 0.1 Pathological tumor stage (reference: <=pT1) pT2 1.71 1.07, 2.74 0.03 1.48 0.91, 2.42 0.1 0.84 0.59, 1.19 0.3 0.89 0.62, 1.28 0.5 1.63 0.90, 2.94 0.1 1.20 0.65, 2.23 0.6 1.60 1.06, 2.43 0.03 1.23 0.80, 1.90 0.3 pT3/4 3.74 2.72, 5.13 <0.001 2.09 1.44, 3.03 <0.001 0.68 0.51, 0.90 0.006 0.71 0.53, 0.95 0.02 3.03 2.01, 4.55 <0.001 1.43 0.89, 2.31 0.1 2.11 1.55, 2.87 <0.001 1.21 0.85, 1.74 0.3 Pathological tumor grade (reference: low grade) High grade 3.00 1.93, 4.65 <0.001 1.72 1.07, 2.75 0.03 0.92 0.71, 1.19 0.5 3.62 1.94, 6.75 <0.001 2.16 1.10, 4.24 0.03 2.43 1.63, 3.61 <0.001 1.71 1.12, 2.63 0.01 Variant histology 1.88 1.11, 3.19 0.02 0.93 0.54, 1.63 0.8 0.89 0.50, 1.59 0.7 1.31 0.57, 2.98 0.5 0.99 0.49, 2.01 >0.9 Lymph node involvement 5.66 3.58, 8.93 <0.001 1.96 1.18, 3.27 0.009 0.44 0.22, 0.87 0.02 0.45 0.22, 0.90 0.02 8.30 4.63, 14.9 <0.001 3.48 1.83, 6.64 <0.001 6.00 3.69, 9.74 <0.001 3.31 1.96, 5.59 <0.001 Tumor multifocality 1.39 1.02, 1.91 0.04 1.31 0.94, 1.82 0.1 1.38 1.07, 1.78 0.02 1.32 1.01, 1.73 0.04 1.76 1.18, 2.61 0.005 1.61 1.06, 2.44 0.02 1.28 0.93, 1.76 0.1 Number of lymph nodes removed 1.01 0.99, 1.03 0.4 1.00 0.99, 1.02 0.6 1.01 0.99, 1.04 0.2 1.01 0.99, 1.03 0.5 Positive soft tissue surgical margins 3.04 1.82, 5.08 <0.001 2.01 1.15, 3.49 0.01 0.96 0.51, 1.80 0.9 2.80 1.42, 5.55 0.003 1.64 0.79, 3.39 0.2 1.73 0.91, 3.27 0.09 Lymphovascular invasion 3.85 2.84, 5.21 <0.001 1.73 1.20, 2.50 0.003 0.79 0.55, 1.12 0.2 3.93 2.64, 5.85 <0.001 1.91 1.19, 3.07 0.007 2.64 1.90, 3.67 <0.001 1.60 1.09, 2.35 0.02 Concomitant carcinoma in situ 1.52 1.07, 2.16 0.02 1.14 0.78, 1.66 0.5 1.47 1.10, 1.97 0.008 1.46 1.08, 1.97 0.01 1.60 1.02, 2.51 0.04 1.04 0.64, 1.69 0.9 1.37 0.96, 1.96 0.09 Adjuvant chemotherapy 4.52 3.32, 6.16 <0.001 2.33 1.62, 3.35 <0.001 1.02 0.71, 1.46 >0.9 4.42 2.97, 6.58 <0.001 2.10 1.30, 3.39 0.002 2.69 1.91, 3.78 <0.001 1.88 1.26, 2.81 0.002 Adjuvant radiotherapy 2.32 1.42, 3.77 <0.001 1.60 0.96, 2.67 0.07 0.43 0.21, 0.87 0.02 0.40 0.20, 0.82 0.01 1.57 0.77, 3.23 0.2 1.34 0.74, 2.40 0.3 HR = hazard ratio, CI = confidence interval. cancers-15-01409-t003_Table 3 Table 3 multivariable linear and logistic regression analyses predicting intraoperative blood loss, hospital length of stay, overall complications, and major complications in a multiple-imputed and propensity-score-matched cohort of 756 patients treated with radical nephroureterectomy for UTUC. Intraoperative Blood Loss Hospital Length of Stay Overall Postoperative Complications (Clavien-Dindo Classification 1-5 ) Major Postoperative Complications (Clavien-Dindo Classification >=3) Univariable Multivariable Univariable Multivariable Univariable Multivariable Univariable Multivariable Characteristic Beta 95% CI p-Value Beta 95% CI p-Value Beta 95% CI p-Value Beta 95% CI p-Value OR 95% CI p-Value OR 95% CI p-Value OR 95% CI p-Value OR 95% CI p-Value Surgical approach (reference: open RNU) Laparoscopic RNU 95 -66, 256 0.2 95 -64, 254 0.2 -1.2 -2.3, -0.06 0.04 -1.1 -2.2, -0.02 0.047 0.86 0.60, 1.23 0.4 0.89 0.62, 1.28 0.5 0.50 0.32, 0.79 0.003 0.50 0.31, 0.79 0.003 Robotic RNU -127 -289, 34 0.1 -140 -299, 20 0.09 -6.2 -7.3, -5.0 <0.001 -6.1 -7.2, -5.0 <0.001 0.52 0.35, 0.75 <0.001 0.53 0.36, 0.78 0.001 0.26 0.15, 0.44 <0.001 0.27 0.16, 0.46 <0.001 Age 6.1 -0.70, 13 0.08 0.06 0.01, 0.11 0.03 0.00 -0.05, 0.05 >0.9 1.01 0.99, 1.02 0.3 0.99 0.97, 1.01 0.4 ASA (reference: 1) 2 -232 -519, 55 0.1 1.0 -1.1, 3.2 0.4 1.82 0.85, 3.91 0.1 1.79 0.82, 3.90 0.1 2.54 0.76, 8.49 0.1 2.07 0.61, 7.04 0.2 3 -44 -331, 243 0.8 -1.0 -3.1, 1.2 0.4 2.12 0.99, 4.56 0.05 2.10 0.97, 4.56 0.06 2.53 0.76, 8.47 0.1 2.13 0.63, 7.22 0.2 4 -216 -662, 230 0.3 1.8 -1.5, 5.2 0.3 7.56 2.54, 22.45 <0.001 7.51 2.48, 22.78 <0.001 10.27 2.52, 41.89 0.001 8.16 1.95, 34.24 0.004 BMI -9.6 -22, 2.6 0.1 -0.23 -0.32, -0.14 <0.001 -0.20 -0.28, -0.11 <0.001 1.00 0.97, 1.03 >0.9 0.98 0.95, 1.02 0.4 Gender (reference: male) Female 192 52, 332 0.007 187 49, 326 0.008 0.65 -0.42, 1.7 0.2 0.71 0.51, 0.98 0.04 0.70 0.50, 0.98 0.04 0.85 0.56, 1.30 0.5 Side (reference: left) Right -45 -178, 87 0.5 -0.53 -1.5, 0.48 0.3 0.83 0.62, 1.13 0.2 0.59 0.39, 0.87 0.01 0.60 0.40, 0.91 0.02 Neoadjuvant chemotherapy -42 -475, 392 0.9 -4.6 -7.9, -1.3 0.006 0.39 0.11, 1.37 0.1 0.00 0.00, 0.00 >0.9 Surgery duration 0.76 0.11, 1.4 0.02 0.78 0.13, 1.4 0.02 0.00 0.00, 0.01 0.09 1.00 1.00, 1.00 0.7 1.00 1.00, 1.00 0.2 Lymphadenectomy performed 100 -39, 239 0.2 -0.05 -1.1, 1.0 >0.9 0.81 0.59, 1.12 0.2 0.80 0.52, 1.22 0.3 Number of lymph nodes removed 2.6 -6.5, 12 0.6 -0.04 -0.11, 0.03 0.3 0.99 0.97, 1.01 0.5 0.98 0.95, 1.01 0.2 Perioperative intravesical chemotherapy instillation - - - -1.9 -3.4, -0.46 0.01 -1.6 -3.0, -0.30 0.02 0.88 0.56, 1.39 0.6 0.78 0.42, 1.44 0.4 Pathological tumor stage (reference: <=pT1) pT2 102 -93, 296 0.3 109 -84, 301 0.3 1.3 -0.20, 2.7 0.09 1.0 -0.32, 2.4 0.1 1.59 1.03, 2.46 0.04 1.77 1.13, 2.77 0.01 1.17 0.68, 2.04 0.6 pT3/4 287 140, 435 <0.001 275 129, 421 <0.001 2.9 1.8, 4.0 <0.001 2.9 1.9, 4.0 <0.001 1.18 0.84, 1.66 0.3 1.20 0.84, 1.71 0.3 0.85 0.54, 1.34 0.5 Beta = regression coefficient, OR = odds ratio, CI = confidence interval. 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PMC10000229 | Human-animal bonds, by providing social support, have been shown to improve the health and wellbeing of pet owners, especially those experiencing a crisis situation. The human-animal bond for people in crisis situations is complex and multifaceted, as it has shown to improve health, whilst it can also discourage people from seeking help, due to fears of leaving their pet behind. The purpose of the study is to capture and to assess the role of the human-animal bond for people in crisis situations. Semi-structured interviews were conducted with pet owners involved in the RSPCA NSW Community Programs (n = 13) in 2021 and 2022. The findings of the study indicate that the human-animal bond is highly valued by people experiencing crisis situations, that the human-animal bonds can affect people's ability to seek help or refuge, and that the human-animal bond helps people to recover after a crisis. The findings suggest that community crisis support services, prison systems, hospital systems, emergency housing, and government legislation should recognize and aim to preserve this bond to provide the best help for people experiencing crisis situations. human-animal bonds companion animal pet crisis situations social support coping mental health multifaceted This research received no external funding. pmc1. Introduction Pet owners often regard their pets as friends, confidants, and family, with reference to their emotional and social intelligence . Human-animal bonds have been associated with improvements to human health . The social support hypothesis proposes that these improvements to health are the consequence of the support provided by the social connection to their pets . Pets directly provide their owners with social support themselves, or by promoting human social interactions . The mechanisms by which pets provide social support are hypothesized to be the catalyzation of interpersonal connections , companionship , and the encouragement of exercise . Research has shown that the most common household pet species include cats, dogs, reptiles, fish, birds, and rodents . These pets all provide companionship, and can catalyze interpersonal connections based on a common interest in that animal . However, dogs were shown to be more likely than other species to encourage physical activity in the form of exercise and interpersonal connections through chance interactions that occur on dog walks . Human-animal bonds have been associated with improvements to physical and mental health . The biopsychosocial model conceptualizes health as the disruption or enhancement to the interrelated social, biological, and psychological factors of health . Human-animal bonds provide social support to human beings, reducing anxiety, depression, and stress . This in turn prevents associated physical health responses such as the hyperactivity of the sympathoadrenal medulla system and the hypothalamic-pituitary-adrenal axis, which if prolonged, can encourage chronic disease and mortality . A broad range of investigations have found that human-animal bonds improve mental health by providing social support, which consequently improves physical health . However, as it is possible for the mechanisms for social support to differ between pet species, their contribution to health can also vary. While cats have been shown to provide better companionship to their HIV-positive owners than dogs , dogs have been associated with a significant increase in exercise and enhanced physical health for their owners . There are limited studies exploring how the species of a companion animal mediates the effect on human health . The human-animal bond can have both positive and negative influences on the health of people experiencing crisis situations. Crisis situations are short-term overwhelming situations that disrupt an individual's normal state, causing stress and social isolation . Key crisis situations relevant to the concept of the human-animal bond are homelessness , domestic violence survivorship , incarceration , and hospitalization . Research has indicated that the social support provided by pets is vital for the health of highly stressed or socially isolated people . Recent studies have illustrated that people experiencing any of these key crisis situations tend to be socially isolated and highly stressed, and that the social support provided by human-animal bonds can be pivotal for their health and coping . However, for people in crisis situations, caring for an animal can become a barrier to seeking help, as this may entail leaving their pet in a dangerous environment or surrendering them . If a pet is left behind when escaping a crisis situation, negative cognitions associated with their pet's safety can hinder a persons' recovery . People experiencing homelessness have profound emotional connections to their pets, and this social support is vital to their endurance in inhospitable environments . Studies have shown that people experiencing homelessness would rather forgo accommodation than relinquish their pet to a shelter indefinitely . Similarly, animal intervention programs have illustrated that a human-animal bond can motivate inmates to reduce recidivism and inmate violence, while promoting the development of life skills, a sense of self, and healthy behaviors, which improve coping and recovery after leaving jail . While there is limited literature assessing the impact of the human-animal bond on hospitalization, it has been shown that human-animal bonds are associated with improved cardiovascular recovery post-surgery . Furthermore, the responsibilities of pet ownership can delay an individual seeking healthcare . Domestic violence survivors' pets are crucial supporters, confidants, and allies . However, domestic violence perpetrators can use violence against pets as a coercive control measure, making the pet a barrier to escaping a domestic violence situation . The Royal Society for The Prevention of Cruelty to Animals New South Wales (RSPCA NSW) provides a range of community programs that provide temporary housing and care for pets whose owners are escaping crisis situations, allowing the pet owners to focus on their own wellbeing, recovery, and safety . Within the program, pets are placed in foster homes or emergency boarding through private pet boarding facilities or RSPCA NSW shelters for up to three months while their owner seeks refuge or recovers . These community programs also provide personalized case management, financial assistance, and access to veterinary treatment . Our study aims to develop a better understanding of the role of human-animal bonds for clients of the RSPCA NSW Community Programs experiencing crisis situations, through a qualitative research approach . This enhanced understanding will be used to better inform policy and service provision. This qualitative research creates the foundations of future investigations, and was developed to understand its research subject, rather than investigate predicted outcomes. Inductive studies have revealed nuanced insights into the accounts of people experiencing homelessness, domestic violence, and incarceration . To the author's knowledge, there are currently no studies that holistically explore and characterize the role of the human-animal bond for people in crisis situations by capturing both the positive benefits to health, and the negative effects on help-seeking behaviors. Our study aims to fill a gap in the existing literature by exploring the perspectives of people in crisis, to create a comprehensive and multifaceted understanding of the role of human-animal bonds for people experiencing crisis situations. 2. Materials and Methods 2.1. Sample All clients from the RSPCA NSW Community Programs were eligible to participate in the study, and they were invited by their case worker to participate as they were discharged from the program. Clients from three Community Programs were eligible to participate: (1) Domestic Violence, (2) Aged Care, and (3) Emergency Boarding and Homelessness. Participation was optional and was with informed consent. 2.2. Semi-Structured Interviews The semi-structured interviews were conducted to capture the interviewees' perspectives on the role of the human-animal bond for people experiencing crisis situations (Table 1). Interviews were conducted in two rounds and were completed via telephone by two members of the research team (GM and KO). The first-round interviews were conducted from March to May 2021. The second-round interviews were conducted between August and September 2022. 2.3. Qualitative Data Analysis Interview transcripts were subjected to a thematic analysis using an inductive approach. All interviews were transcribed in full, using the transcription tool provided by Microsoft Word. The interview audio was subsequently reviewed manually to correct any mistakes to the transcription. To analyze the interview transcripts, the data were coded using the computer-assisted qualitative data analysis software NVivo (released in March 2020) . The coding process was treated as a non-linear system and re-reviewed frequently to ensure that the interpretation privileged the perspectives of the respondents. The transcripts were manually assessed, line by line . Using NVivo, codes (subthemes) were created by attaching annotations, concepts, and thematic domains to specific words and excerpts from the interview transcript . Subsequently, relationships were identified between the created codes (subthemes), and these relationships were used to aggregate closely interrelated codes (subthemes) to develop major codes (themes). Afterwards, major codes (themes) were selected and integrated into meaningful summaries that address key components of the role of the human-animal bond for people in crisis situations. This complete non-linear coding process is depicted in Figure 1. Themes were then reviewed to determine whether they were distinct to the clients from a particular program (e.g., Homelessness) or a specific pet species, and addressed accordingly. Major codes and summaries were then organized to build a comprehensive report of theories that address the role of the human-animal bond for people experiencing crisis situations, as depicted in Figure 2. 2.4. Ethical Approval Ethical approval was granted by the University of Sydney Human Research Ethics Committee (Project Number 2020/856). 3. Results Thirteen clients participated in the study; one client who experienced domestic violence, one client who experienced homelessness and domestic violence, nine clients who had been hospitalized (six from the Aged Care program and three from the Emergency Boarding program), and two clients who had been incarcerated. Of these same 13 clients: seven clients had dogs, and six clients had cats. The thematic analysis identified three major themes; (1) the human-animal bond is highly valued by people experiencing crisis situations, (2) human-animal bonds can affect people's ability to seek help or refuge, and (3) the human-animal bond helps people to recover after crisis. Each theme is made up of 2-5 subthemes, which explore significant elements of their main theme. The themes and subthemes identified from the interviews related to the role of the human-animal bond are reported below, with illustrative quotes. Pseudonyms have been used to protect the identities of interview participants and their animals. 3.1. The Human-Animal Bond Is Highly Valued by People Experiencing Crisis Situations (Theme 1) Clients expressed that the human-animal bond was highly valuable during their crisis experience. Participants clearly identified that at the time of crisis, their animal's companionship improved and bolstered their mental health and ability to cope. Human-animal bonds also catalyzed interpersonal connections during crisis situations, which improved mental health and the ability to cope. In contrast, the absence of a pet during the crisis negatively affected mental health and coping. 3.1.1. Pet Companionship during a Crisis Situation Improves Mental Health and Coping (Theme 1, Subtheme 1) Participants reported that their animals provided social support in the form of companionship during their crisis situation. Participants' animal companions provided non-judgmental and unconditional love, which alleviated the social isolation caused by their crisis situation. Fraternal, friendly, and familial descriptors illustrate the strength and closeness of these connections. "Gosh, she's basically the only friend I have in the world. I don't have anybody else, I have Rosie--it's wonderful. Rosie listens to my sad stories, she listens to my happy stories. She jumps around joyously and barks when I'm happy and sits there and mopes with me when I'm not".--Barney "Well, that's what all animals do, unconditional love".--Susan "Ah, everything. It's just like a child. Just like one of my kids. I mean, of course my children are people, they're humans, but he thinks he's a human".--Anne Participants reported how companionship was associated with improvements to their mental health. Companionship from their pet was described as mentally grounding, alleviating stress and anxiety, and renewing mental strength, which allowed individuals to persevere and to cope with their crisis situation and life. "She's registered with the local council as a companion, and she's been a constant companion and she's been a constant form of support and she gives me so much occupational therapy that I actually rely on her and she's only a cat".--Sara "When you're in the situation I was in, you're sort of in a crisis situation--you're not connected to anything, you know? You're quite alone and even though there are services around you and that sort of stuff. The cats kept me focused on what I needed to do".--Susie "Well, it helps alleviate, that stuff <stress, depression, and anxiety>, like a great deal of it, yes".--Sole. 3.1.2. Interpersonal Connections Catalyzed by Pets Improve Mental Health during Crisis Situations (Theme 1, Subtheme 2) A participant who was incarcerated reported how pets can create social connections during a crisis situation. She described how these interpersonal connections were associated with improvements to mental health, by relieving stress and by being associated with positive cognitions such as joy and happiness. "I must have sounded freaking insane because you know I would make stories up about them, like them being an Olympic champion and stuff like that and my girlfriends would laugh. And I'd say, "I wonder what they're doing now?".--Susie 3.1.3. Separation from Pets during Crisis Can Cause Stress and Anxiety (Theme 1, Subtheme 3) Participants described how the absence of their pet while they were in a crisis situation caused them to be stressed or anxious because they were concerned about their animal's safety or wellbeing, and that this was detrimental to their mental health and physical health. "I was actually very, very distraught without him because he's the one I talk to and tell things to because he doesn't tell anybody else and he's not judgmental. He's just awesome".--Anne "When I'm not with her when I'm in hospital, I'm always worrying about how when she's like kept in the kennel with the RSPCA, I'm always worrying about her and asking about her. Asking about her and sometimes call the RSPCA and see how she is. Yeah so, I will always take care of her, and they will always take good care of her".--Sole "I get very lonely without them. I just spent seven weeks in hospital, and I hate to put them into RSPCA to look after them for me and I really missed them".--Daniel "But that's why straight away I got organized with the nurses they contact <RSPCA> and they were able to pick her up. Because when I'm worried, I'm stressed it's not good for my heart to get stressed, they said it's not good. That's the problem I have. But I'm handling it. I can look after her still you know?".--Gavin 3.2. Human-Animal Bonds Can Affect People's Ability to Seek Help or Refuge (Theme 2) Human-animal bonds can affect people's ability to seek help or refuge. Clients expressed how the safety of their pet was a key determinant in deciding to seek help, and that without the assured safety of their pet, they would not carry out help-seeking behaviors; for example, organizing to have surgery or seeking accommodation. A domestic violence survivor expressed how their pets were used as a form of coercion and control to prevent help-seeking behaviors, or the animals were used by the abuser to exact revenge. The RSPCA NSW and its community programs provided a trustworthy service which assured the safety of their pets and arranged payment programs which provided relief. This allowed participants to focus on seeking help or refuge for themselves. 3.2.1. Pet Ownership Can Dissuade Help-Seeking Behaviors (Theme 2, Subtheme 1) Participants described how their fear of losing or abandoning their pet made them reluctant or unable to seek help. Clients identified that they had a responsibility to their pets in looking after them, and therefore, seeking help that required surrendering them was associated with guilt and heartache. Clients reported that they would rather forgo necessary treatments or stay in unsafe situations, rather than lose their animal. "I had to have spinal surgery and of course I couldn't afford the $55 per night to have [her boarded]. So, it was either find someone who can look after her for next to nothing or surrender her and the second option just did not appeal to me in any way, shape, or form".--Barney "We all love our pets and the last thing that most of us want is to have to part with them because we're put in a situation for a while. That's the worst, because then we'll find a house and it'll be like "our dog is gone"".--Anne "I know it's forever. It's not, I'm not going to like you next week so I can give you back. The commitment you make to a dog has to be forever or not at all. That's my view anyway".--Angela "Yeah, it's just. It used to. I don't know, just used to get me a bit quite depressed over the number of times I've had to be going now to hospital and. Yeah, it's just the upset it creates in my house every time I go 'cause, I've always gotta find somebody to look after my dogs or find somewhere that'll take them while I'm in the hospital. And then I'll worry about them all the time I'm in hospital".--David Participants who were domestic violence survivors specifically identified how domestic violence perpetrators can use pets as a form of coercion and control to prevent help-seeking behaviors or exact revenge. "No [my perpetrator had not harmed my dogs previously], not that I'm aware of. No, definitely not. But he would lash out at me, basically. But I wasn't at home, so the next best thing was something that he knew that I really loved--my animals. He knew that's how he could get to me".--Daisy 3.2.2. RSPCA (Theme 2, Subtheme 2) Participants identified that RSPCA NSW was a key factor in encouraging the decision to seek help by keeping them connected to their pets and providing a payment plan. Similarly, participants reported that the assured safety of their pet provided by RSPCA NSW was associated with relief and the ability to focus on escaping from crisis and their own recovery. The safety of their pet was a major priority and requirement in the help-seeking process. "Really really happy. You have no idea how happy I am. And everyone I know, all my girlfriends all said I can't believe that you actually kept the cats. I said, you know if I'm paying this off until I'm 80 it doesn't matter. Right? Because what needed to happen, happened".--Susie "Yeah, yeah. I mean, 'cause, we spent so much time together. No, it was great when <my RSPCA case worker> sent me the photos over. I was like, I know she's OK. I know she's OK. You're looking after her, OK, looking out, or someone is looking after and she's not here by yourself all the time. That's what I was most worried about that she was here by herself".--Clementine Participants identified how the cost of boarding was associated with an inability to seek help, and how RSPCA NSW providing a payment program helped them to overcome this challenge. "Thank God, RSPCA is around, I can't believe the program, yeah it just covers everything it really does. It's good... I just walked out of the RSPCA that day and said "yeah cool, OK".... I knew that they'd be safe 24/7".--Susie "Because there would be an awful lot of people like me who adore animals who couldn't afford to pay $50 a night who needed surgery who would have had to either not have the surgery or release the animal to its fate, which usually little animals like that don't have a very good fate. So, there you go. But we don't have to go there because the RSPCA solved that problem for me".--Barney 3.3. Human-Animal Bonds Help People to Recover after Crisis (Theme 3) Clients expressed throughout their interviews that their relationships with their animals were important to their recovery after their crisis experience. Clients expressed that their relationship with their animals provided routine and companionship, and catalyzed connections with other people. Social support in general bolstered and improved their mental health, which aided recovery. 3.3.1. Pet Ownership Encourages Structure and Routine, Which Improves Recovery and Mental Health after Crisis (Theme 3, Subtheme 1) Participants reported that their relationships with their animals were important for their recovery from the crisis situation, because pet-related routines such as walking, feeding, or playing; and even basic chores such as cleaning food bowls and litter trays, provided structure to their life, post-crisis. Respondents identified how the requirements and routines associated with pet ownership motivated them to get through the day, and provided a sense of purpose. "They made me come home every night. Be there to feed them at you know--oh Lucy gets a bit whiny if it gets to about 10 past 4--she's like a Labrador! But you know, be fed by 6 o'clock every single dad. I'm up every single morning to put food in their bowls. Their bowls are washed out religiously. These are the things I've got to do every day. That's what the cats mean to me. They basically took the place of an antidepressant" .--Susie "Well, sometimes when I don't feel like going out and I can't be bothered going out today. I look at them and I think Oh, well I've gotta go. I've gotta go, gotta. I've gotta go and I've got to do this and that for them".--Clementine Participants reported that the structure and routines were therapeutic, and encouraged self-care behaviors. These self-care behaviors were described to have improved mental health by reducing stressors and improving mood, which aided recovery, post-crisis. "Well, they keep me on my toes and always give me something to do. And when you think of occupational therapy, that's just like second nature when you've got a pet you care for. It is an occupation in a way. It's not a chore but it's something you've got to do. It gives you an outlet.... Yeah! Structure! That's the word, yeah yeah. I know it's very beneficial as a therapy".--Sara "You know if you're stressed out, you might stay home. I might just want a lie around but I'm not that kind of guy. I like to get up early in the morning. Sometimes 5-6 o'clock. Get Bella breakfast for her. Yeah, it makes my day, you know? For me and her. You know some people stay in bed, they are done with that and don't care. But I care about Bella. I care about her, so I care about myself!".--Gavin 3.3.2. Pet Companionship Improves Recovery and Mental Health, Post-Crisis (Theme 3, Subtheme 2) Participants reported that the companionship provided by their animals was important to their recovery from their crisis situation. The presence of the animal was important to their wellbeing and recovery. Post-crisis participants identified that animal companionship was connected to their sense of self, and was like sharing their life with a person. "They've been my companions for the last 6-7 years, it's the reason why I get up in the morning to be honest... It wasn't all lost, like the girls were coming with me and that made it sort of better... [My cats] are the reason I feel carpet under my feet in the morning. Over the years my life got to the point where I've lost so much, and not just material stuff and money, but all the other shit that goes with it, and [my cats] were my anchor".--Susie "I just hope that I can keep going maybe say another 10 or 12 years, which will probably be roughly the life expectancy of a dog like Rosie and if that works out we'll both hopefully go somewhere at the same time. Hopefully together".--Barney Participants reported how this companionship was associated with mental health improvements by attenuating stressors, helping with the recovery of mental health post-crisis, and renewing internal strength and the desire to keep going with life. "Oh of course it does [improve my mental health]! My goodness gracious without a dog I really wouldn't be here. I actually wouldn't want to be here".--Barney "Well, I just appreciate them even more than I already did. It made the bond stronger between us, our little relationship, and I'm glad that they have each other as well. Because they helped each other through the healing process".--Daisy "They give me a pet to cuddle. They give me something to care for, to look after. I think that as you grow older--because I looked after my elderly parents for 12 years--as you get older you need something to look after, it keeps you going. They looked to me for food. I feed them, I cuddle them. I see to their hygiene. And they give me some sort of purpose in life. And that is so important as you get older. Something to do, someone to look after, someone to tend to. So you're not sitting, fixating on yourself all the time. Sort of like a diversional therapy".--Sara 3.3.3. Interpersonal Connections Catalyzed by Pet Ownership Improve Mental Health and Recovery Post-Crisis (Theme 3, Subtheme 3) Participants reported that interpersonal connections were promoted by human-animal bonds, post-crisis. "If you do have an animal or pet [it] increases your chance of having longer lasting relationships with a companion in the future".--Paul "Friends on the internet on Facebook, no there's lots of different Facebook pages. It's great, great. Not a great amount just personal friends on Facebook, but I've never met. But you know, really close because we had the same condition, some same health condition".--Sole "We started chatting one day about a year ago I guess when she sort of pulled me up when I was taking Rosie for a walk... But every afternoon, 2-3 km she used to take her and Rosie loves that and that's something that I can't do. So that 'fit' is very very good for all of us".--Barney Participants reported how interpersonal connections were associated with mental health improvements, because human connections created because of their relationship with their animal promoted positive emotions and elevated mood. "All the community, the people inside the community here, some of them get along with her, mostly all of them. The ones who are trusted and a few friends".--Gavin "People stop with their dogs... kids are coming up... Everybody knows him. Probably 'cause I've got a big mouth".--Simone "<It keeps me> mentally healthy, you know we laugh, we share funny names and pictures of cats and things like that. Cats doing strange things yeah".--Sole. 3.3.4. Pets Encourage Physical Exercise, Post-Crisis (Theme 3, Subtheme 4) Participants who owned dogs regularly reported how their pets encouraged them to go on walks in a post-crisis setting. "I push her to the park, but whenever she [was] in the park I let her go off-leash you know, let her run around and we go and do some shopping and come back with the stroller with her. It takes me like 1 h to the park, 1-2-3 h. It makes my day like when I have nothing to do. It makes me feel relaxed. You know stressed out all gone. Do you understand?".--Gavin A participant identified how their cat motivated them to care for their own physical health by discouraging smoking. "That's why I gave up smoking because they won't come near you, and why would they?".--Susie Despite a thorough discussion of physical health, clients frequently discussed physical health in terms of how much exercise their pet was encouraging them to do, rather than the physical condition of their body. "Physical health... I don't really go on as much walks because I've been struggling to breathe because of the chest infection".--Paul "I don't move around well so it's not much physical exercise, but mentally yeah, they've been absolutely great".--Arthur 3.3.5. Absence of Their Pet, Post-Crisis, Attenuates Recovery and Mental Health (Theme 3, Subtheme 5) Participants identified how the absence of their pets would be associated with worse mental health and limited recovery, commonly connected to a lack of desire to live. "If I hadn't had the dogs here, I don't know what would have happened. I think I just would have cut the top, the bundling, lost the plot completely. I just wouldn't have been able to cope".--Daniel "I probably wouldn't'... I probably would be dead if I didn't have her. She's my lifeline".--John 4. Discussion This explorative study examined the role of the human-animal bond for people experiencing crisis situations. Our thematic analysis of semi-structured interview transcripts identified three major themes: (1) human-animal bonds are highly valued by people experiencing crisis situations, (2) they can affect people's ability to seek help or refuge, and (3) they can help people recover after crisis. These major themes identify three distinct phases where human-animal bonds are important for people experiencing crisis. 4.1. Human-Animal Bonds Are Highly Valued by People Experiencing Crisis Situations (Theme 1) A key aspect of the role of human-animal bonds for people experiencing crisis situations is its ability to provide companionship and to catalyze interpersonal connections, which by improving mental health enhances an individual's ability to cope with the crisis. This highlights the importance of keeping pets connected to their owners throughout and beyond their crisis situations. Companionship provided by animal companions was found to be important for those experiencing crises, by providing non-judgmental and unconditional love, that alleviated the social isolation caused by their crisis situation. This finding corresponds with existing literature that has illustrated that people experiencing domestic violence and homelessness felt isolated and emotionally distressed. Furthermore, these studies highlighted how the non-judgmental and unconditional love provided by pet companionship was a profound form of emotional support that could attenuate these feelings of isolation and emotional distress . Our results indicate that animal companionship improved mental health, allowing individuals to persevere and to cope with their crisis situation and life. This result supports a broad range of investigations that illustrate that companionship provided by human-animal bonds can improve mental health by reducing anxiety, depression, and loneliness . Cleary et al.'s (2020) integrative review found that people experiencing homelessness described how animal companionship improved their mental health and their ability to cope with homelessness. Overall, our findings extend contemporary understandings of animal companionship by illustrating how companionship attenuates social isolation, improves mental health, and is an invaluable part of coping for people experiencing all crisis situations. Our study found that for a participant who was incarcerated, pets catalyzed social connections during their crisis situations. These interpersonal connections were associated with improvements to mental health, by relieving stress and by causing feelings of joy and happiness. To the author's knowledge, there is limited research investigating the importance of interpersonal connections for people experiencing crisis situations. However, this finding supports the literature that has demonstrated that pet ownership can act as a common quality that facilitates the creation of social support networks which protect against social isolation and that support the release of negative emotions which improve health . Our result of only being described by an individual experiencing incarceration is most likely due to the fact that during crisis situations such as hospitalization, homelessness, and domestic violence, making connections with new people is very difficult. This finding should be explored appropriately in future studies. Our findings demonstrate that the absence of a pet while a person is in a crisis situation caused them to be stressed or anxious, and that this was detrimental to their mental and physical health. A wide range of literature has similarly described that the fear of losing pets is highly traumatic and is associated with anxiety . Our findings extend this understanding to illustrate how the absence of a pet during a crisis intensifies fear and anxiety, and can make people focus on the uncertainty of the wellbeing of their pets. 4.2. Human-Animal Bonds Can Affect People's Ability to Seek Help or Refuge (Theme 2) Pet owners experiencing a crisis situation are reluctant or unable to seek help or refuge because they fear losing or abandoning their animal. Hence, it is important to include pets and to consider them as part of the family unit when helping people to access services during a crisis situation. The RSPCA NSW's Community Programs were a key factor in encouraging the decision to seek help by keeping pet owners connected to their pets and by providing a payment plan, allowing them to focus on themselves. This result supports a range of studies that have illustrated that the fear of losing a pet can dissuade people experiencing homelessness , domestic violence , and hospitalization from seeking help. Our results identified that domestic violence perpetrators can use pets as a form of coercion and control to prevent an individual seeking help or to exact revenge. This finding is corroborated by Haden et al. (2018) and Hardesty et al. (2013) that found that the abuse of companion animals is used as a coercive tactic by domestic violence perpetrators to control their partners by creating an environment of fear, dependency, and helplessness . The current study found that the RSPCA NSW provided a trustworthy service that by assuring the safety of their pet and arranging payment programs, provided relief, allowing people to focus on help-seeking behaviors. This finding extends previous research by highlighting how help-seeking behaviors can be encouraged by keeping people connected to their pet. 4.3. Human-Animal Bonds Help People Recover after a Crisis (Theme 3) A key benefit of human-animal bonds during crisis recovery are their ability to improve mental health and wellbeing by providing structure and routines, and companionship, and catalyzing interpersonal connections. The importance of pets encouraging routines and structures has been identified in research investigating the human-animal bond and elderly people . Hui Gan et al. (2020) highlighted how pet-related routines such as feeding, playing, and grooming provide structure to the lives of elderly pet owners. We found that this benefit was consistent amongst the clients of all the RSPCA NSW programs, and not just for elderly clients. Our results indicate that the structures and routines provided by human-animal bonds were therapeutic and encouraged self-care behaviors that improved mental health and recovery. This finding is supported by Hayden-Evans et al. (2018), which found that pets, by encouraging routine and structure, can provide a life purpose that aided in the development of recovery skills. There is limited research investigating the importance of routine for people experiencing crisis. However a key challenge for people post-crisis is recovering in an unfamiliar and confusing environment; therefore, pet-related routines are valuable in providing structure to navigate this new environment and to enhance recovery . Our study found that human-animal bonds were important for a recovery from crisis situations by providing companionship, which was connected to a sense of self. To our knowledge, there are no studies that identify the importance of animal companionship for an individual's sense of self, post-crisis. However, the importance of animal companionship to a sense of self has been described in studies of people in aged care. Hui Gan et al. (2020) highlighted how the importance of the human-animal bonds for people in aged care is connected to their perception of themselves and how they are to spend the rest of their life with another living being. Therefore, this finding extends the definition of animal companionship for people experiencing crisis situations to be connected to a sense of self and sharing a life with their pet. Our findings demonstrate that animal companionship by attenuating stressors was associated with mental health improvements, recovery post-crisis, and renewing internal strength and the desire to keep going with life. Studies such as Cleary et al.'s (2020) have found that people experiencing homelessness described how animal companionship was important to their recovery after finding accommodation because of positive effects on their mental health. However, there are currently no studies that identify the importance of animal companionship to a sense of self and the improvement of mental health. Overall, our findings extend contemporary understandings of animal companionship by illustrating how companionship is connected to a sense of self, improves mental health, and is an invaluable part of recovery for people experiencing all crisis situations. Our results indicate that human-animal bonds promote interpersonal connections post-crisis, and that this contributed to improved mental health. This finding supports the literature that demonstrates that pet ownership can act as a common quality that facilitates the creation of social support networks . Social support networks protect against social isolation and support the release of negative emotions, which improve health . Studies have shown that having a larger number of interpersonal connections or friends was associated with better mental health, and that this is connected to the creation of social support networks . Socially isolated individuals may still struggle with making connections in person, and participants highlighted the importance of online communities such as Facebook. This finding is corroborated by Newman et al. (2019) who found that online communities such as Facebook or online forums can allow socially isolated individuals to regain a sense of social inclusion and belonging. Unlike during crisis situations, for people recovering from crisis situations, this finding was described by all participants, demonstrating that in a post-crisis environment, people can more effectively create interpersonal connections promoted by their pets. Our findings indicate that post-crisis, dogs encouraged their owners to go on walks, whereas cats did not. Research has shown that dogs are more likely to encourage physical activity in the form of exercise than other common pet species . Furthermore, pets dissuaded cigarette smoking which would improve physical health. To this author's knowledge, this paradigm has not been explored and should be explored in future studies. A noteworthy, unexpected aspect of this finding is that participants did not identify any direct influences on their physical health. Despite thorough discussion, most participants interpreted physical health to mean how much exercise their pet was encouraging them to do, rather than the physical condition of their body. This could be due to the fact that social media and pop-culture reinforce an understanding of physical health to be connected to exercise and physical activities, such as going running or going to the gym . This finding was unlike a broad range of investigations that found that the human-animal bond improved physiological health markers such as blood pressure, serum triglycerides, heart rate variability, and cholesterol levels . The lack of responses indicating improvements to physical health could also be because qualitative studies are inadequate at perceiving the quantitative variables in the beforementioned studies that indicated the physical health of the body. Therefore, future studies could attempt a mixed-methods model to better address physical health. Ultimately, as descriptions of physical health were scarcer and more limited than mental health, this finding alludes to the fact that people experiencing crisis situations find that the role of human-animal bonds is more focused on mental health improvements rather than on physical health improvements. Our study found that the absence of a pet post-crisis was associated with predictions of worse mental health and connected to suicidal ideation and limited recovery. This reflects commonly reported phenomena in the crisis literature where people experiencing homelessness and domestic violence highlight that the absence of their pet would take away their life purpose and attenuate their recovery from their crisis situation . 5. Limitations A key limitation of the study is the possibility of sampling bias. A person who is going to accept an interview from the RSPCA NSW is likely going to have successfully, coped, escaped, and recovered from their crisis situation because of the RSPCA NSW Community Programs. Therefore, participants in this study were likely to endorse the RSPCA. Future studies could improve understandings of the human-animal bond for people experiencing crisis situations by interviewing people who did not successfully cope, seek help, or recover from crisis situations, and contrast this with people who were successful. There are unequal numbers of clients from different crisis situations, which may have led to the overrepresentation or underrepresentation of certain phenomena. Future studies should attempt to consolidate the perspectives of people who have experienced incarceration, homelessness, and domestic violence. Participants in this study tended to be older than 60 years of age and described phenomena common to research investigating human-animal bonds and elderly people. Future studies should investigate participants from a variety of age groups to determine whether the described phenomena are due to the ages of the participants. Participants in this study only owned cats and dogs, limiting the studies' generalizability to the roles of all pets. Companionship and the catalysis of interpersonal connections are not unique to only dogs and cats . Future studies could explore more pet species to see if there are differences in the way in which particular animal species provide social support. Our study found that participants interpreted physical health to mean how much exercise their pet was encouraging them to do, rather than the physical condition of their body. As this was a qualitative interview-based study, physical measures used in conceptually similar quantitative studies such as platelet activity, triglyceride levels, and hyperactivity of the hypothalamic-pituitary-adrenal axis could not be measured. Therefore, future studies could attempt to incorporate a mixed-methods model that incorporates both the perspectives of individuals in crisis situations and also the physical quantitative measures of their health. 6. Implications The human-animal bond is integral for coping, escaping, and recovering from crisis, and the social support that it provides is crucial for the mental wellbeing of their owners. This finding has important real-world applications. In Australia, most domestic violence shelters, homeless shelters, and rental accommodation do not accept pets , resulting in animal shelters being inundated with pets surrendered by owners who are unable to secure affordable or pet friendly accommodation . Furthermore, in Australia, a large percentage of individuals who had experienced crisis situations did not know about services that would provide them with aid . The findings of this study suggest that crisis support services, prison systems, hospital systems, animal welfare/health organizations, and government departments and agencies should collaborate to keep owners connected to their pets throughout their crisis situation, or incorporate better systems for managing pets. Moreover, government policy and community-based programs should aim to consider pets as part of the family unit in their planning or management of people in crisis, as the described impacts to their health and willingness to seek help could be fundamental to their health and survival. Programs such as the RSPCA NSW Community Programs protect the vital connections between pet owners and pets, and ultimately serve as a lifeline for the coping, escape, and recovery of people experiencing crisis situations. 7. Conclusions This study, by investigating and analyzing the accounts of people experiencing crisis situations, has created a comprehensive framework for understanding the role of human-animal bonds for people experiencing crisis situations. The social support of human-animal bonds provided through companionship and interpersonal connections is fundamental to the mental health and coping abilities of people during crisis situations. A fear of losing their pet or endangering them can discourage help-seeking behaviors. However, the provision of appropriate resources, in our case, through the RSPCA NSW, that mediate costs and that keep the individual connected to their pet, can encourage help-seeking behaviors. The social support of human-animal bonds provided through structure and routine, and through companionship and interpersonal connections, was important for mental health and their recovery from crisis. In contrast, the effects on physical health were inconclusive and should be explored further. Ultimately, the findings from our study clearly highlight the importance of keeping pet owners connected to their pets throughout and beyond their crisis experience. Services such as the RSPCA NSW Community Programs should be supported and expanded. Crisis support services, prison systems, hospital systems, animal welfare/health organizations, and government legislation should attempt to preserve and to strengthen the human-animal bond to best support the wellbeing, coping, and recovery of people experiencing crisis situations. Author Contributions Conceptualization, K.O. and G.M.; methodology, K.O., J.R. and G.M.; formal analysis, K.O., J.R. and G.M.; data curation, K.O. and G.M.; writing--original draft preparation, K.O.; writing--review and editing, J.R., S.L., B.H. and G.M.; supervision, S.L., B.H. and G.M. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study protocol was approved by the University of Sydney Human Research Ethics Committee (protocol code 2020/856, 19 January 2021). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement The data presented in this study (de-identified interview transcripts) are available on request from the corresponding author. The data are not publicly available to protect the privacy of research participants. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Non-linear qualitative coding process diagram. Figure 2 Qualitative coding and theory development diagram. animals-13-00941-t001_Table 1 Table 1 Examples of semi-structured interview questions. Questions What companion animals do you care for, and what do they mean to you? Can you tell me a bit about life before [ANIMAL] came to RSPCA? What is life like now? What difference has RSPCA made for you? What is the biggest difference in your life now? How has having a pet affected your health? What value could you put on this change? (Asked for a stated preference) What aspect of pet ownership is most important to your day-to-day life? What aspects and influences in your life impacted your decision to seek help? How much of this difference in your life is due to RSPCA? Can you estimate a percentage? What would have happened if it weren't for RSPCA? Are you aware of other organizations offering a similar service to the RSPCA program? Secondary Interview Questions Human-animal bonds are valuable to people during a crisis Could you tell me a bit about your story and how you came to be involved with the RSPCA program? Could you describe some instances where your pet has supported you during your crisis situation? How would you describe your wellbeing or state of mind during this situation, did your pet influence this in any way? Can you recall any instances where your pet improved your physical health, where physical health refers to the condition of your body? Help-seeking behaviors What helped you seek help? How did being a pet owner influence your ability and desire to seek help? What aspects and influences in your life impacted your decision to seek help from the RSPCA? Human-animal bonds are important to recovery, post-crisis How has having a pet affected your health? What aspects of pet ownership are most important to your day-to-day life? How has your pet affected you after your crisis situation? How would you describe your wellbeing or state of mind after your crisis situation, did your pet influence any of that? Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000230 | Since 2005, a mandatory L. Hardjo control programme (LHCP) has been in place for Dutch dairy herds. Almost 100 percent of dairy farms participate and have an L. Hardjo-free status. In 2020 and 2021, the number of outbreaks seemed to increase as compared to the previous years. In this study, we evaluated the effectiveness of the national LHCP in the Netherlands during 2017-2021. Cases of new infections in herds with an L. Hardjo-free status in the LHCP were described, including the role of risk factors for the introduction. Both the percentage of dairy herds with an L. Hardjo-free status that purchased cattle from herds without a free status and the number of purchased cattle increased over the years. A between-herd cluster evaluation showed that between 2017 and 2021, a suspected infection was detected 144 times in 120 dairy herds. In 26 cases (26 herds, 0.2%) new infections were identified, including within-herd transmission. No infection clusters were identified, indicating that infections never led to local transmission between dairy herds. The introduction of cattle from non-free herds appeared to be the cause of all L. hardjo infections in herds participating in the LHCP. Therefore, the national LHCP seems to be highly effective in the control of infections in dairy herds. leptospirosis Leptospira serovar hardjo control programme purchase risk factor disease control surveillance dairy serology import This research received no external funding. pmc1. Introduction Leptospirosis in cattle is predominantly caused by Leptospira interrogans serovar Hardjo type prajitno and Leptospira borgpetersenii serovar Hardjo type bovis. Both serovars have zoonotic potential, mainly for farmers and farm workers . To our knowledge, serovar Hardjo-type prajitno has not been reported in cattle in the Netherlands, but serovar Hardjo-type bovis has been described in both cattle and cattle farmers in the Netherlands . Leptospira infections can be acquired via direct or indirect contact with the urine of infected individuals or with contaminated water. The pathogen enters the body through mucous membranes, skin cuts, or abrasions . Possible clinical signs of leptospirosis in cattle include abortion, infertility, and a poor milk yield, but infections can also remain asymptomatic . The clinical signs of human L. Hardjo infections include febrile illness, pulmonary haemorrhage, and renal failure . L. Hardjo infections in cattle can be detected in body fluids, including serum, milk, and urine. Direct detection methods, such as culture and polymerase chain reaction (PCR), may fail to detect intermittent shedding of leptospires by chronically infected carriers. Antibody tests, including microscopic agglutination tests (MAT) and enzyme-linked immunosorbent assays (ELISA), are, therefore, more effective to support a clinical diagnosis in cattle and to determine disease prevalence in herds. MAT is the World Organization for Animal Health reference test for cattle, and is often required for export purposes, but serological responses can be missed in chronic cases. ELISA is a more sensitive method that shows persistent seroresponses, which can also be used to detect L. Hardjo antibodies in individual or bulk milk samples . The main risk factors for the introduction of L. Hardjo into dairy herds are contact with the urine of newly introduced infected animals into a herd (for example, after purchase) and indirect local transmission by, for example, contaminated surface water . In 1989, the herd seroprevalence of leptospirosis in dairy cattle in the Netherlands was 35% . A voluntary control programme with the aim to eliminate this zoonotic disease from individual cattle herds has been in place in the Netherlands since 1994 . This L. Hardjo-free control programme (LHCP) is based on testing for L. Hardjo antibodies in serum and bulk milk and is carried out by Royal GD (Deventer, the Netherlands). An L. Hardjo-certified free status has been required by the Dutch Dairy Board for herds delivering milk to Dutch dairy plants since 2005. Currently (2022), 99.9% of all Dutch dairy herds and 33% of non-dairy herds participate in the LHCP. The vast majority of these herds are classified as being L. Hardjo-free . Since L. Hardjo-free status became obligatory for dairy herds only sporadic introductions occurred , with the exception of the years 2020 and 2021, when an increased number of introductions of L. Hardjo were identified . Leptospirosis is a notifiable disease in the Netherlands. Therefore, introductions of L. Hardjo are registered in the Dutch Cattle Health Surveillance system (CHSS) . The aim of the study reported in this article was to evaluate the effectiveness of the national LHCP in the Netherlands in the context of early detection of new infections and prevention of transmission of L. Hardjo between herds between 2017 and 2021. Cases of new infections of L. Hardjo in dairy herds with an L. Hardjo-free status were described, including the role of known risk factors for introduction, such as livestock purchases and local between-herd transmission. 2. Materials and Methods 2.1. L. Hardjo-Free Control Programme Although both dairy and non-dairy herds participated in the LHCP, we focused on the population of approximately 15,000 participating Dutch dairy herds over the period from 2017 to 2021. In 2021 there were 1.57 million dairy cows registered in the Netherlands, with an average herd size of 110 cows (>2 years old). This included almost 100% of the Dutch dairy herds and only excluded a very small number of herds that did not sell their milk to dairy plants that are members of the Dutch Dairy Board. The total number of dairy herds in the Netherlands declined during the study period, resulting in a decreasing number of participants. The LHCP was described in detail by Santman-Berends et al. . In short, herds are assigned the L. Hardjo-free status after an initial assessment with all negative test results consisting of individual L. Hardjo antibody testing. Surveillance of the subsequent L. Hardjo-free dairy herds is based on L. Hardjo antibody testing of (1) bulk milk samples three times a year, (2) post-movement sera from cattle introduced from herds without L. Hardjo-free status, (3), and clinically suspected animals, including aborted cattle. Mandatory serum testing of introduced animals from non-free herds is assigned directly after the introduction of animals into the receiving herd and has to be completed within eight weeks. L. Hardjo antibody tests in bulk milk and sera are performed using the PrioCHECK L. Hardjo Ab Plate Kit (Thermo Fisher Scientific, Applied Biosystems, Lelystad, the Netherlands) . For both the serum and bulk milk ELISA, sensitivity is >95%, and specificity is >99%. In the event of a positive or inconclusive antibody test result of the introduced cattle or clinically suspect cattle, the L. Hardjo-free status of the receiving herd is suspended, and confirmatory testing is mandatory . Seropositive animals have to be removed from the herd, followed by a bulk milk test four weeks later or by serological testing of three contact animals, to attain certified-free status. In case of a positive or inconclusive outcome of this subsequent testing, individual testing of all animals in the herd is mandatory to investigate possible transmission of L. Hardjo within the receiving herd. In the event of a positive bulk milk screening test, the L. Hardjo-free status is suspended, and a second bulk milk sample is taken for confirmation of transmission. If the transmission is confirmed, the herd status is changed to 'infected', and all animals in the herd are treated on a single day with a single intramuscular dose of dihydrostreptomycin . All participating herds in the LHCP that purchased cattle from an infected herd are notified to perform post-movement serum testing of those cattle. After treatment, the herd status changes to 'controlled'. To survey for transmission of L. Hardjo in herds with a 'controlled' status, a seronegative sentinel group of five animals of >=2 years old are tested serologically every six months. A herd can retrieve the L. Hardjo-free status after a new assessment of individual serum tests of all animals >1 month of age. 2.2. Definitions The following definitions were used:Purchase: Introduction of an animal into a herd from a Dutch herd, whether or not a financial transaction occurred; Import: Introduction of an animal into a herd from a herd located outside the Netherlands; High risk animals: Animals introduced from herds not participating in the LHCP, or from herds participating in the LHCP without an L. Hardjo-free status; Suspended herd status: Temporary loss of a certified-free status requiring action to regain the herds' free status. There are multiple reasons for suspending the certified free status, such as a delay in submitting required samples, introduction of new cattle, or a positive test result; Suspected herd: A herd that is suspected to have an L. Hardjo infection, indicated by an antibody positive serum or bulk milk sample, and mandatory confirmatory testing to detect spread has not been completed yet; Infected herd: A herd in which spread of L. Hardjo was proven by two positive L. Hardjo antibody tests in consecutive bulk milk samples (within a period of eight weeks), or an L. Hardjo antibody positive serum test result followed by either a positive bulk milk test result, or three serum samples taken four weeks after removal of the positive animal . This is also referred to as a new infection in this manuscript; Neighbouring herds: Infected and/or suspected herds that were located within a 5 km radius of each other; Cluster: A group of neighbouring herds with an overlapping maximum potential infectious period (see Section 2.4 for more detail). 2.3. Data Collection and Study Period Herd data and L. Hardjo status were obtained from an automated certification administration system at GD. This system receives near real-time (daily) cattle movement information from the national identification and registration database (Netherlands Enterprise agency, Assen, the Netherlands). The movement data, combined with LHCP status data, enabled identification of cattle transfers from non-free herds during the period 2017-2021. L. Hardjo status of herds could change during the study period. The total number of participants of the programme, and status data of participants, were therefore described for the last day of each of the evaluated years. Risk factors, including purchase, import, and local transmission, were evaluated by using data on numbers of introduced cattle, the L. Hardjo status of the herds of origin, and dates of introduction. Herds of origin not participating in the LHCP could be located either outside or within the Netherlands. If the L. Hardjo status from the herd of origin was unknown, a possible positive L. Hardjo herd status was assumed, and the introduced cattle were characterized as high-risk animals. The proportion of certified L. Hardjo-free herds that introduced high risk animals, and the number of high-risk animals introduced per herd per year, are descriptively presented. A chi-square test was used to evaluate whether or not the average number of high-risk cattle introduced into a herd varied between years. 2.4. Cluster Evaluation Cluster evaluation was used to investigate transmission between neighbouring herds. Herds with a suspected and infected status were included. Herds within a 5 km radius of each other were classified as neighbouring herds. For each neighbouring herd the duration of the maximum potential infectious period was calculated. A herd was classified as suspected if either a milk sample or a serum sample tested positive. For herds with a positive bulk milk sample, the maximum potential infectious period was defined as one month before the last negative bulk milk sample until eight weeks after the last positive sample that was taken in response to the positive bulk milk sample . The limit of eight weeks was chosen because, in the LHCP, positive animals have to be removed from the herd within eight weeks after confirmation of an L. Hardjo infection. For herds where only positive serum samples were found, it was not known when the positive animals would have become infectious. Therefore, based on a best-case scenario, two maximum potential infectious periods were defined. In the best case, the start of the maximum potential infectious period was assumed to start on the day the first positive sample was taken. In the worst case, the start was assumed to be eight weeks earlier. This time frame was chosen because, in the LHCP, a high-risk animal must be tested within eight weeks after introduction. In both cases, the maximum potential infectious period ended eight weeks after the last positive serum sample was taken . Overlap in time and space of their maximum potential infectious periods were described for all neighbouring herds. If there was an overlap, both herds were grouped into the same cluster. The time of purchase or importation of cattle, particularly whether or not it occurred within the preceding year, was determined for each herd in the identified clusters. This indicated if the most probable route of introduction of infection was through purchase, import, or otherwise (for example, local transmission). It was also assessed whether or not the identified clusters remained if the 5 km radius was reduced to 3 km or 1 km. All analyses in the cluster evaluation were performed in R-studio version 4.1.3 with the aid of the libraries lubridate, data.table, and tidyverse for analytical purposes . 3. Results 3.1. Participation in the LHCP On average, 97% of the Dutch dairy herds participating in the LHCP had an L. Hardjo-free status between 2017 and 2021 . The remaining 3% of the herds had a temporary suspension of their free status due to the need to provide evidence of freedom, either because of the purchase of animals or a delay to comply with the LHCP surveillance scheme. In sporadic cases, herds temporarily lost their free status due to a new infection of L. Hardjo. Both the percentages of dairy herds with an L. Hardjo-free status that imported cattle, and the total number of imported or purchased cattle, increased over the investigated years, with a peak in 2019 . The proportion of purchases or importations of high-risk cattle, in relation to the total purchases and importations, did not change during the study period. Of all herds that purchased or imported high-risk cattle, 53% performed this only once, 21% twice, 25% 3-10 times, and 1,5% more than 10 times per year. The number of introduced high-risk cattle per event was significantly (kh2: p < 0.05) higher in 2019 (15.9), 2020 (13.9), and 2021 (12.9) compared to 2017 and 2018 (10.5 and 11.0, respectively) . 3.2. Cluster Evaluation During the study period, 120 dairy herds, out of approximately 15,000 participating dairy herds, were classified as a suspected or infected herd at, in total, 144 occasions (Table 1). Of all the 120 herds with either a suspected or infected status, 21 herds were identified as herds where the infection overlapped in time and space. This was the case for both the worst-case scenarios for herds with only positive serum samples. Therefore, the results are only presented once. Nine clusters of neighbouring herds were identified (<5 km) (Table 1). If this distance was reduced to 3 km, only four clusters remained, and with a distance of 1 kilometre, no clusters remained. Positive serum samples were taken from animals that were imported recently at 12 of the 21 clustering herds. In 7 other of these 21 herds, positive samples were taken from animals that were purchased from herds in the Netherlands that were not, or not yet, assigned L. Hardjo-free status. For the remaining two herds, no link could be found with the recent introduction of cattle. These two herds belonged to two different clusters. 3.3. New Infections with L. Hardjo Of the 120 herds that were suspected of infection or infected, 26 were classified as infected in the LHCP, given that within-herd transmission was observed. These 26 herds were not neighbouring herds and did not have L. hardjo infections that overlapped in time and space. Most of these were detected in 2020 and 2021. These 26 herds were not part of any cluster between 2017 and 2021 (Table 2). 3.3.1. Introduction of Animals from Herds Not Participating in the LHCP In twelve of the 26 cases, the infection was likely to be introduced into the herd by the introduction of imported animals. In seven of these cases, antibodies were detected by mandatory serological screening of recently introduced animals. In five other herds, the imported animals were all antibody-negative during mandatory screening, but the following bulk milk samples were antibody positive. Three of the infected herds had recently introduced cattle that were purchased from Dutch (non-dairy) herds that did not participate in the LHCP. The sera that were tested for mandatory screening tested L. Hardjo antibody-positive, and the spread of the infection occurred after the introduction of the antibody-positive animals. 3.3.2. Introduction of Animals from Dutch Herds Participating in the LHCP In nine cases, the introduction of leptospirosis occurred after the purchase of cattle from L. Hardjo-infected farms. Eight of these nine cases followed purchases from one single herd (Herd A). In this infected herd, imported cattle had been introduced previously and were screened four days after their introduction into the herd, resulting in negative tests. Therefore, the free status of Herd A was initially retained. However, in the next bulk tank screening of this herd L. Hardjo antibodies were detected. In the period between the last negative bulk milk screening and the result of this positive bulk milk test, the farm sold cows with L. Hardjo-free status. A herd receives the "infected" status only when a positive bulk milk sample is confirmed, and all purchasing herds are notified to serum test purchased cattle that might be infected with L. Hardjo. However, before receiving the result of the positive bulk milk test, the farmer stopped milking and sold all the cows, which were then moved to different herds. No confirmation of the first positive bulk milk sample could be performed. Without a confirmative test result, the herds' L. Hardjo status did not change from suspended to "infected", according to the LHCP regulations. The farmers that purchased cattle from Herd A during the L. Hardjo-free status were, therefore, not initially notified to screen the purchased animals for antibodies against L. Hardjo. However, after the detection of leptospirosis in one of these herds, all participants in the LHCP that purchased cattle from Herd A were advised to perform serological screening, which resulted in a total of eight infected farms. In the ninth case, a cow was imported and tested seropositive in the subsequent mandatory screening. This cow was then sold before treatment of the herd and introduced into another dairy herd. In both herds in which the animal was introduced, the infection was detected in the mandatory serum test and confirmed by a bulk milk test result. 3.3.3. Cases Not Related to Introduction of Cattle In two herds with new infections, no high-risk cattle were recently introduced. In the first case, a group of 30 heifers broke out to a neighbouring non-dairy herd that did not participate in the LHCP. In the second case, the herd was located at the same address as a non-dairy herd that did not participate in the LHCP. In both cases, leptospirosis may therefore have been introduced via local transmission. This hypothesis could unfortunately not be substantiated as the non-dairy herds were not screened for the presence of L. Hardjo. 4. Discussion The findings of this study showed that, during the five-year study period, a suspected introduction was detected 144 times in 120 dairy herds that participated in the LHCP. Due to the surveillance scheme in place in the LHCP and quick actions taken by farmers; furthermore, the within-herd transmission was prevented in the majority of these herds. In our study, imported vaccinated animals could have been marked as animals with suspected infection in the study period, which may have led to an overestimation of the number of suspected infections. Within-herd transmission occurred in 26 herds participating in the LHCP in the Netherlands in the five-year study period, which was only 0.2% of the total number of participants (approximately 15,000). In almost all cases, leptospirosis was found to be introduced into the herds via the introduction of high-risk cattle originating from herds that did not participate in the LHCP (import and purchase) or without an L. Hardjo-free status. The introduction of cattle from herds that were not certified-free thus appeared to be the most important risk factor for the introduction of L. hardjo in herds participating in the LHCP in the Netherlands. In the years 2019-2021, more herds either imported or purchased cattle from herds without an L. Hardjo-free status compared to 2017-2018, which was most likely associated with new Dutch legislation that resulted in less youngstock held per herd. The increased occurrence of importations and purchases led to a slight increase in the number of new infections. In the cluster evaluation, a standardized definition for the maximum potential infectious period was used. By using this standardized definition, a worst-case situation was assumed as measures taken by farmers to remove infected animals were not taken into account. Nevertheless, the fast removal of positive animals reduces the maximum potential infectious period. In the cluster evaluation for one cluster was seen that the introduction of leptospirosis could not be directly linked to importations or purchases from herds without an L. Hardjo-free status. Upon closer examination, it appeared that in the first herd of this cluster, measures were taken to remove infected animals, thus reducing the maximum potential infectious period. By reducing this period, the two suspected herds did not have an overlapping maximum potential period anymore. For all other herds in the clusters, the introduction of leptospirosis could be directly linked to importations or purchases from herds without an L. Hardjo-free status. Therefore, local transmission of leptospirosis (with serotype Hardjo) between dairy herds participating in the LHCP was not observed and appeared unlikely. This suggests that the role of neighbouring farms was negligible in the transmission of L. Hardjo between Dutch dairy herds participating in the LHCP between 2017 and 2021. The cluster evaluation only included dairy herds participating in the LHCP because the L. Hardjo status in non-participating herds was unknown. The non-dairy herds, for which participation in the LHCP was not required, often have an unknown L. Hardjo status and, therefore, could be a potential source of infection for local transmission. Nevertheless, the true L. Hardjo herd-level prevalence in the Dutch non-dairy sector is probably low. In the most recent national prevalence survey in 2013, only 0.8% of the non-dairy herds tested positive for L. Hardjo . The risk for transmission from the non-dairy to the dairy sector is also assumed to be limited due to regulations in the LHCP. Given the results of this study, we conclude that the LHCP is effective in the control of L. Hardjo in the Netherlands. Nevertheless, participation in the LHCP does not completely prevent new cases of leptospirosis. Therefore, some additional measures may be useful to minimize the risk of the introduction and spread of infection. For example, the interval and timing of testing could be optimized. Cattle infected and introduced from non-free herds may already transmit the pathogen before seroconversion and/or before the mandatory serum testing is performed , for example, when the animals contract the infection during the last month before the transfer or during transport. Moreover, it cannot be excluded that cattle may fail to respond serologically. In our study, we observed some cases in which the initial post-movement serological tests were negative after the introduction of high-risk animals. Nevertheless, at the subsequent routine surveillance sampling, which is part of the LHCP, the herd tested positive. As no other possible routes of infection were identified on these farms, the introduction of high-risk cattle seemed to be a plausible source of infection. In these cases, suspected infection was detected by regular bulk milk screening. Thus, if sera are taken <30 days after introduction, this may be too early to detect seroconversion . In these specific cases, infections could have been detected earlier if the animals would have been (re)-tested >30 days after introduction into the herd. It is advised (but not mandatory) in the LHCP to serologically screen cattle before introduction into a herd (pre-movement testing), in addition to the mandatory screening after introduction . It is, however, unknown how many herds perform pre-movement testing and how effective this would be. To further reduce the risk of transmitting the pathogen in the LHCP, animals might be quarantined until a negative test result of a second screening moment at >30 days after introduction into the herd. However, since testing twice and including additional quarantine measures is labour-intensive and costly, making these measures mandatory could reduce farmers' compliance with the programme rules. Therefore, it was decided that these measures are not mandatory, but are advised in the LHCP . If quarantine measures, in combination with testing at suggested times, would have been applied, the majority of the new infections found in 2017-2021 may have been prevented. However, these measures would probably not have been cost-efficient given the low prevalence and incidence of L. Hardjo in the Netherlands, resulting in only low economic losses. It was the first time since 2005 that a case such as Herd A, where multiple farms became infected by one single farm within the LHCP, was observed. An additional measure to the LHCP regulations could be to notify purchasing herds that previously bought cattle from an L. Hardjo-free herd where a single positive bulk milk test cannot be confirmed by a second bulk milk test. The specific herd that was mentioned in this paper, Herd A, stopped milking, and when the first bulk milk sample was found, this result could not be substantiated with a second sample given that the herd was no longer producing milk, and thus purchasing farms were not notified. If in such cases, a single positive test result of regular bulk milk sampling would have been followed up by notifying the purchasing herds, the infections in the other eight herds may have been detected earlier. The purchasing herds could have been notified at an earlier stage to test the serum of the purchased animals. This could have prevented the eight infections related to the purchase from Herd A. This case represents a calamity within the LHCP, which could be prevented by implementing the improvements listed above. However, this case is currently considered to be a very rare event where there was an unlikely succession of coincidences. Leptospirosis has a broad geographical distribution and, in some areas, for example, in tropical countries, it is an endemic disease, causing high mortality and morbidity . In this manuscript, we focused on L. Hardjo in cattle in the Netherlands, but risk factors for leptospirosis may be different in other countries, and therefore, control of leptospirosis may require a different approach. For example, Leptospira serovars that circulate may differ in different parts of the world . Survival of Leptospira in the environment may vary due to climate factors, surface water and soil composition, and different (vector) animal contact structures may exist . Although leptospirosis is a difficult disease to control in the tropics, components of the LHCP could be implemented to control and possibly eradicate the disease on a herd level. Vaccination is applied to control leptospirosis in cattle in several other countries . However, vaccines for cattle against L. Hardjo are not registered in the Netherlands, and it would not be a cost-effective intervention in a situation where almost all dairy farms are certified free, and the incidence is at a very low level. High costs for vaccination, added to the costs involved with testing for participation in the LHCP, could result in a major loss of support for the LHCP by farmers. Additionally, vaccination would interfere with the ELISA tests used in the LHCP. This also argues against vaccination as an option in the Netherlands, although it has been shown that vaccination may be an effective measure in the control of Leptospirosis in other countries. 5. Conclusions In this study, the effectiveness of the national LHCP in the Netherlands between 2017 and 2021 has been described with an emphasis on the early detection of new infections. Despite high numbers of imported and purchased cattle, the number of new infections remained low, with an incidence of 0.2% in the herds participating in the LHCP over a five-year period. Due to the early detection of new infections, the role of local between-herd transmission appeared minimal, as indicated by the fact that no clusters of infected herds in time and space were identified. It is therefore concluded that, although some calamities may occur sporadically, the national LHCP in the Netherlands is highly effective in the control of L. Hardjo infections. Acknowledgments The authors would thank Linda van Wuijckhuise for providing historical data on the LHCP and Bert de Roo, Maarten Weber and Paul Wever for critically reading this manuscript. Author Contributions Conceptualization, K.M.J.A.v.d.B., M.A., N.D.F. and I.M.G.A.S.-B.; methodology, K.M.J.A.v.d.B., M.A., N.D.F. and I.M.G.A.S.-B.; software, Stata and R.; K.M.J.A.v.d.B., N.D.F. and I.M.G.A.S.-B.; validation, K.M.J.A.v.d.B., N.D.F. and I.M.G.A.S.-B.; formal analysis, K.M.J.A.v.d.B., N.D.F. and I.M.G.A.S.-B.; investigation, K.M.J.A.v.d.B. resources, K.M.J.A.v.d.B.; data curation, K.M.J.A.v.d.B., N.D.F. and I.M.G.A.S.-B.; writing--original draft preparation, K.M.J.A.v.d.B., M.A., N.D.F. and I.M.G.A.S.-B.; writing--review and editing, K.M.J.A.v.d.B., M.A., N.D.F. and I.M.G.A.S.-B.; visualization, K.M.J.A.v.d.B., N.D.F. and I.M.G.A.S.-B.; supervision, I.M.G.A.S.-B.; project administration, K.M.J.A.v.d.B.; All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The herds or groups of herds included in this study may be identifiable from their unique combination of explanatory variables. Therefore, the datasets analysed in this study cannot, and will not, be made available to readers. Conflicts of Interest All authors work at GD Animal Health, which coordinates this control programme. Figure 1 Control actions following detection of antibody positive cattle or bulk milk screening in the Leptospira Hardjo Control Programme. Figure 2 Graphical depiction of the definition of the maximum potential infectious period of a herd, if it became suspected due to (A) a positive bulk milk sample or (B) a positive serum sample. Figure 3 Percentages of dairy herds participating in the Leptospira Hardjo Control Programme with the free status (light blue columns) and the percentage that temporarily lost the status from 2017 to 2021 (dark blue line). Figure 4 Percentages of dairy herds with a L. Hardjo-free status that purchased cattle from either herd with a lower L. Hardjo-free status and/or from herds abroad per year from 2017 to 2021. Figure 5 Box-and-Whisker plot of the numbers of introduced cattle per purchasing herd per year in L. Hardjo-free dairy herds originating from herds with a lower L. Hardjo status (including import). animals-13-00831-t001_Table 1 Table 1 Results of cluster evaluation of dairy herds participating in the L. Hardjo control programme. Clusters were classified according to the year in which the first positive sample occurred in the cluster. Year # Herds in LCHP # Herds with >=1 positive Test * Cluster < 5 km Cluster < 3 km Cluster < 1 km # Clusters # Herds per Cluster # Clusters # Herds per Cluster # Clusters # Herds per Cluster 2017 16.355 10 1 2 0 - 0 - 2018 15.792 15 0 - 0 - 0 - 2019 15.295 47 4 4 3 2 2 3 4 2 2 0 - 2020 14.919 31 3 2 2 2 0 - 0 - 2021 14.450 26 1 2 1 2 0 - * Herds with multiple positive tests per year were classified once in that year. Herds with positive test in multiple years were included in multiple years. Therefore, the sum of all herds with >=1 positive test during the study period (129) is higher than the total number of unique herds with >=1 positive test (120). animals-13-00831-t002_Table 2 Table 2 Number of new infections of L. Hardjo from 2017 to 2021 in the Netherlands classified by most plausible introduction route. Most Plausible Introduction Route 2017 2018 2019 2020 2021 2017-2021 Cattle purchased from herds not participating in LHCP * Import 0 1 2 6 3 12 Purchase 0 0 0 1 2 3 Cattle purchased from herds participating in the LHCP (regardless of status) * Purchase 0 0 1 6 2 9 Not related to introduction of cattle 0 1 0 1 0 2 Total of new infections 0 2 3 14 7 26 * In most cases, the introduction of cattle occurred in the same year as the detection of infection, for infections related to introduction of cattle. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000231 | Cancers (Basel) Cancers (Basel) cancers Cancers 2072-6694 MDPI 10.3390/cancers15051354 cancers-15-01354 Editorial Editorial: Autologous and Allogeneic Stem Cell Transplant in Cancer Therapy Sharma Nidhi 1* Efebera Yvonne A. 2* 1 Division of Hematology, The Ohio State University, Columbus, OH 43210, USA 2 Department of Hematology, Blood and Marrow Transplant, OhioHealth, Columbus, OH 43214, USA * Correspondence: [email protected] (N.S.); [email protected] (Y.A.E.) 21 2 2023 3 2023 15 5 135413 2 2023 15 2 2023 19 2 2023 (c) 2023 by the authors. 2023 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ). pmcOver the last 10 to 20 years, there have been significant improvements in the fields of both autologous and allogenic transplantation. The upper age limit for hematopoietic stem cell transplantation continues to increase for both autologous SCT (ASCT) and allogeneic HCT (allo-HCT). The improvement in supportive management and development of novel agents has led to increases in survival outcomes in patients undergoing ASCT for multiple myeloma and lymphoma. Advances in conditioning regimens, the expanding use of alternative donor stem cell sources such as haploidentical stem cells and cord blood, and the use of modern T-cell depletion strategies such as post-transplant cyclophosphamide have led to better survival outcomes and a reduced incidence of graft versus host disease in patients undergoing allo-HCT. This special issue, which comprises 12 papers, addresses various aspects outlining the roles of ASCT and allo-HCT in the treatment of hematological malignancies, new advancements pertaining to their use and the challenges they pose when deciding on the optimal practice. The paper by Jiang et al. was a retrospective analysis on patients who underwent allo-HCT to better understand how survival has changed over the years. The authors divided the patients into groups based on the year of transplant. The data showed that both progression free and overall survival increased over the years. Five-year graft-versus-host disease/relapse-free survival (GFRS) also increased from 6% to 14% in the latter years. The authors attributed this change to advances in supportive care and treatments focused on the mitigation of graft versus host disease (GVHD) and relapse . For allogenic transplantation, tacrolimus, a calcineurin inhibitor that prevents T-cell activation, is often used for GVHD prophylaxis. However, there is variability in the serum concentrations of tacrolimus (TAC), and little is known on the impact of early TAC levels on acute GVHD (aGVHD). The retrospective study (2002-2016) by the same group studied the effect of early post-transplantation tacrolimus concentration on the risk of acute GVHD. It was reported that achieving >=10 ng/mL during the first week of allo-HCT may mitigate the risk of aGVHD. However, levels of >11 ng/mL beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse . Graft versus host disease is a serious but common complication associated with allo-SCT as a result of donor T-cell mediated stem cells that attack immunocompromised host tissues. The treatment of aGVHD involves a high dose of corticosteroids, which suppress the immune system and put patients at an even greater risk of infectious complications , and potential viral reactivation complications. Despite this increased risk, there are little published data focused on the efficacy of cytomegalovirus (CMV) prophylaxis for patients who develop aGVHD. Wolfe et al. reported on the efficacy of letermovir to prevent clinically significant CMV infection (CS-CMVi) among allo-HCT patients who developed aGVHD in a single center retrospective study. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (p < 0.001), reduced non-relapsed mortality (p = 0.04) and improved overall survival (p = 0.04), suggesting that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD. Dybko et al. aimed to identify predictive and risk factors associated with the increased occurrence of the BK virus-related hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HCT). A significant correlation was observed between HC incidences after HCT, BK viremia and viruria, and aGVHD occurrence. Furthermore, the level of BK virus DNA in serum at day +21 (>0.75 x 103) significantly impacted the patients' survival time . Allo-HCT therapeutic efficacy is mainly dependent on immune alloreactivity mediated by donor lymphocytes infused with the stem cell graft, the so-called graft versus leukemia (GVL) effect. Disease recurrence is the major obstacle to the success of allo-HCT, as patients with high-risk acute leukemia and MDS have a high risk of relapse after allo-SCT . Prophylactic donor lymphocyte infusion (DLI) has been shown to reduce the relapse rate but at the cost of increased GVHD . Tsirigotis et al. tested the safety and efficacy of a novel method of prophylactic DLI based on prolonged repetitive administration of low lymphocyte doses. When extended for up to 3 years, low-dose pro-DLI administered every two months is safe and effective in reducing relapse rate in patients with high-risk acute leukemia (AL). The data showed that repeated and prolonged DLI administration resulted in relapse prevention, perhaps by inducing a long-lasting anti-leukemic effect . Gutierrez et al., in a retrospective analysis, showed that it may be a curative option in relapsed/refractory (R/R) mantle cell lymphoma with a low cumulative incidence of relapse (CIR). They showed that it might be a better option for fit patients, using human leukocyte antigen (HLA)-identical (related or unrelated) or haploidentical related donors and without previous transplantation. In another study, Tsai et al. compared the outcomes of post cyclophosphamide with or without anti-thymoglobulin and GCSF-primed bone marrow plus peripheral blood stem cells (GIAC). They showed that the mGIAC approach may be a preferential choice for patients with low/intermediate-risk diseases in the view of non-relapse mortality (NRM), CIR, or overall survival (OS) . For multiple myeloma (MM), ASCT is more commonly used compared to allo-HCT. In this issue, three papers were published (two original article and one review). Jordan et al. performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992 to 2016 . Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years, there was a statistically significant improvement in both progression-free-survival (PFS) and OS, which was primarily attributed to the inclusion of novel therapies and post-transplantation maintenance. Importantly, significant survival improvements were seen in patients <=65 years and >65 years old. Baertsch et al. reported on the outcome after salvage high-dose chemotherapy (HDCT)/ASCT following re-induction treatment with carfilzomib/lenalidomide/dexamethasone (KRD). The authors conducted a retrospective analysis of patients that had previously undergone frontline HDCT/ASCT and reported that KRD followed by salvage ASCT were associated with favorable PFS and the response was enhanced by maintenance treatment. Deep remissions achieved with KRD followed by salvage autologous transplantation were associated with favorable PFS and were enhanced by maintenance treatment . In the past years, the therapeutic approaches for patients diagnosed with MM and their respective prognoses have decisively changed with the development of highly efficient new anti-myeloma drugs, such as protosome inhibitors (PI), immunemodulatory drugs (IMID), monoclonal antibodies and CAR-T cells. The review by Greil et al. addresses the role of allo-HCT in MM. The authors discuss data showing that a decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Salvage allo-HCT is recommended, preferentially within clinical trials, for patients with early relapse after first-line therapy including ASCT, and in high risk (HR) constellations according to cytogenetics and stage . Severe acute or chronic GVHD, systemic signs of inflammation and endothelial dysfunction with fluid overload are relatively common posttransplant conditions that are associated with an adverse prognosis and decreased survival due to increased NRM in allotransplant recipients. Previously, it has been shown that there is an association between systemic metabolic profiles and the risk of GVHD, and fluid retention post allo-HCT . Hatfield et al. studied the potential associations between lipidomic profiles and pretransplant inflammation, early fluid overload and later development of aGVHD. Ninety-two consecutive patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were included in the analysis. The results showed that the pretransplant lipidomic profiles differed significantly when comparing patients with and without the risk factors: (i) pretransplant inflammation, (ii) early fluid overload, and (iii) patients with and without later steroid-requiring aGVHD . The pediatric population treated with allo-HCT most frequently develop endocrine complications. The treatments given, consequently, lead to impaired fitness, including exercise-induced shortness of breath, fatigue and reduced participation in physical activity . These symptoms may indicate frailty . Suominen et al. evaluated the physical fitness and prevalence of frailty in male long-term survivors of pediatric allo-transplant. Low muscle strength and a high incidence of frailty were observed in survivors of pediatric allo-HCT. There is a predominant risk of cardiovascular and metabolic diseases in the long-term . 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PMC10000232 | Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions. cardio-oncology cardioprotection cancer immune-checkpoint inhibitors atherosclerosis cholesterol inflammation Italian Ministry of Health Ricerca Corrente fundsThis work was supported by the Italian Ministry of Health Ricerca Corrente funds, titled "Cardiotossicita da chemioterapie, targeted therapies e immunoterapie, diagnosi precoce e cardioprotezione. Ricerca preclinica e clinica" (Linea 6/1). pmc1. Introduction Immune checkpoint inhibitors (ICIs) are increasingly used in oncology to treat multiple malignancies, including melanoma, non-small cell lung cancer, metastatic breast cancer, and others . In most cases, ICIs are monoclonal antibody antagonists of programmed death-ligand 1 (PDL-1) or programmed cell death protein 1 (PD-1) or cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) which are the main drivers of peripheral immune tolerance, even towards tumors . Briefly, ICIs antagonize the inhibition of lymphocyte uptake against tumors, resulting in a lymphocyte-mediated anticancer effect . Recent trials associate ICIs with radiotherapy , standard chemotherapy (anthracyclines or platinum-based anticancer drugs) , targeted therapies (HER-2 blocking agents, TKi and others) , and combination therapies (i.e., PD-1 and CTLA-4 blocking agents) . In brief, combination therapies involving ICIs and standard chemotherapies increase lymphocytic infiltration in neoplastic tissue in a pro-inflammatory microenvironment, which make CD56+ and granular lymphocytes more reactive against tumor cells . However, ICIs therapies are associated with a broad spectrum of endocrine diseases and, albeit, relatively rare cardiovascular side effects , including myocarditis , vasculitis , inflammatory endocrinopathies , mucositis , and arthritis . The main mechanisms of cardiotoxicity are not deeply understood, but NLRP-3/IL-1overexpression, My-D88/TLR4, and cytokine-mediated pathways are still considered to be key orchestrators in ICIs-mediated side effects in preclinical and clinical models . Very recently, atherosclerosis has emerged as a new considerable ICI-s mediated side effect in cancer patients . Briefly, exposure to PD-1 or PDL-1 or CTLA-4 blocking agents increases VCAM-1 and ICAM-1 expression in luminal membrane of vascular endotheliocytes, thus stimulating IL-1, IL-6, and TNF-a levels associated with instability of the atherosclerotic plaque. Interleukins 1 and 6 and TNF-a induce LDL uptake and their oxidation to OX-LDL in endothelial cells . A new key driver of the atherosclerosis process is proprotein convertase subtilisin/kexin type 9 (PCSK9) . Briefly, PCSK9 is a protein with key roles in hepatic low density lipoprotein (LDL) homeostasis, reducing the LDL-receptor density in hepatocytes . When PCSK9 binds LDL receptors, it prevents the correct recycling on the cell membrane after the natural bond with LDL particles. This effect increases plasma LDL levels and its associated cardiovascular risk . PCSK9 inhibitors (antibody-based blocking agents and miRNAs) are currently used in clinical practice to reduce LDL levels in high risk cardiovascular patients, intolerant to statins, in order to reduce cardiac risk . However, extrahepatic functions of PCSK9 are increasingly studied in the last three years, involving cardiomyocyte , endotheliocyte , macrophage, and cancer cell metabolism , shedding light on possible therapeutic uses of PCSK9 inhibitors to new off-label clinical applications in cardio-oncology. This review assesses the current knowledge about how PCSK9 interacts with the immune environment in cancer tissue and how PCSK9 inhibitors could be beneficial in patients treated with ICIs in primary prevention of atherosclerosis. First, we describe how PCSK9 is involved in cancer progression and immune escape. Then, we review current knowledge on how PCSK9 inhibitors reduce atherosclerosis initiation and progression in patients without cancer and the main molecular pathways involved. 2. ICIs Therapy, PCSK9, and Risk of Atherosclerotic Cardiovascular Diseases 2.1. ICIs-Mediated Atherosclerosis The use of ICIs can change the peripheral immune tolerance in different tissues, exposing patients to neuro-inflammatory diseases, visceral obesity, atherosclerosis, and leptin resistance . Preclinical models with deactivating mutations of PD-1 or PDL-1 or CTLA-4 genes are more exposed to atherosclerotic plaques characterized by high levels of VCAL-1, ICAM-1, galectine-3, oxLDL, high macrophage density, and pro-inflammatory cytokines . In brief, the lack of these immune repressor proteins increases atherogenic phenotype mediated by a high uptake of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes in atherosclerotic plaque . These findings led to the hypothesis that ICIs could increase the risk of atherosclerotic cardiovascular diseases (ASCD) in cancer patients . Recent clinical studies have confirmed this hypothesis: patients treated with ICIs for two years have a three times higher risk of developing atherosclerosis compared to other therapies . There are additional observational studies associated with the high risk of unstable atherogenic plaques in cancer patients treated with ICIs compared to the general population . However, more in-depth studies should be performed to clarify if combinatorial anti-PD-1 and CTLA-4 therapies could affect the ASCD risk more than a monotherapy regimen. 2.2. PCSK9 Role in Atherosclerotic Pathogenesis A close correlation between atherosclerosis and PCSK9 has also been observed . In a recent meta-analysis , eleven studies in patients with CVD were analyzed. Notably, patients with established CVD and high PCSK9 levels had a 52% higher risk of future total cardiovascular events than those with low PCSK9 concentrations. Patients with high levels of PCSK9 experienced more than 20% of cardiovascular events compared to low levels . Mechanistically, PCSK9 plays a key role in platelet aggregation and adherence to endothelial cells, endothelial dysfunctions, and atherosclerosis . Genetic studies associated loss of function mutation in PCSK9 gene with high LDL levels and high rates of heart failure . Other studies associated high serum PCSK9 levels to a more necrotic core of coronary atherosclerosis independently from LDL levels . These data indicate extra hepatic roles of PCSK9 that do not involve cholesterol homeostasis. However, Vlachopoulos et al. do not associate PCSK9 levels to cardiovascular events in high-risk patients; they only do so in the general population . Additionally, other research groups associated high PCSK9 levels to patients with stable CVD, but not in patients with ACS . However, there are several other associations between PCSK9 and cardiovascular diseases. First, during myocardial infarction, PCSK9 serum levels are upregulated due to pro-inflammatory processes . Moreover, other studies demonstrated that circulating PCSK9 levels rapidly rise after the initiation of statin therapy , and there is a sustained increase throughout statin use. Furthermore, it has recently been observed that PCSK9 could reduce the efficacy of statin treatment in patients with high cardiovascular risk, by reducing the LDL receptor density on hepatocytes . Furthermore, a recent gender study concluded that white people and Asian people have variants in the PCSK9 gene that may or may not be associated with different LDL concentrations . The main cardiovascular outcomes trials, which will be discussed in the next paragraph, called Evaluation of Cardiovascular Outcomes After an ACS During Treatment With Alirocumab (ODYSSEY) and Further CV Outcomes Research with PCSK9 Inhibition In subjects With Elevated Risk (FOURIER) , analyzed cardiovascular benefits of PCSK9 inhibitors in non-cancer patients, and recruited mostly only white patients. Being a minority in the makeup made up of ascitic patients, it is probable that the effects of PCSK9 inhibitors in white people are not the same due to variations in the genetic profile of different races . 2.3. PCSK9 in Cardiomyocyte and Endothelial Metabolism The PCSK9 gene is located on chromosome 1p32.3 that is expressed in several organs, including the liver, kidneys, small intestine, heart, and cancer cells . The encoded protein is of 692 aminoacids, characterized by three domains: signal domain, pro-domain, and V domain . Interestingly, the key process for maturation and secretion of active PCSK9 is secondary to the cleavage of pro-domain in the S 38 and P47 region . The first clinical evidence on the association between PCSK9 and CV events are based on loss of function or gain of function in PCSK9 gene: patients with gain of function mutations of PCSK9 gene experienced high levels of serum LDL-C, a reduction in LDL receptor levels on hepatocytes (by more than 35%), and premature cardiovascular events compared to non-mutated patients . Contrary, loss of function mutations are associated with low serum levels of PCSK9 and more than 40% reduction of LDL-C with consequent risk reduction in incidences of ischemic heart diseases . PCSK9 is also expressed in cardiomyocytes . Very recent studies described PCSK9 functions in cardiomyocyte autophagy, pyroptosis, ferroptosis, and apoptosis . Detrimental events such as hypoxia, acute inflammation, and heart failure can induce different types of cardiomyocyte cell death through PCSK9 overexpression . Specifically, high cholesterol and insulin levels induce overexpression of PCSK9, which activates DRP-1 in mitochondria triggering autophagy . Moreover, PCSK9 exacerbates mitochondrial ROS production, resulting in the activation of the LKB1-AMPK pathway . Moreover, in cases of OX-LDL intake in the cardiomyocyte, PCSK9 overexpression causes mitochondrial DNA damage, resulting in the activation of NLRP3 inflammasome/Caspase-1/Interleukin-1 pathway . This process activates cardiomyocyte pyroptosis. Increased serum levels of IL-1 and IL-6 directly result in PCSK9 overexpression, which also induces cardiomyocyte apoptosis via caspase-9 and 3 . Another biochemical mechanism of PCSK9 cardiac and endothelial toxicity is mediated by lipid peroxides . Lipid peroxidation, which can be induced by acute inflammation, smoking, and some chemotherapeutic drugs such as anthracyclines, leads to the formation of MDA and 4-HNA by the Fenton reaction . PCSK9 activates the Fenton reaction, whose gene expression is activated by the over-intake of Fe3+ in cardiomyocytes and endotheliocytes . Furthermore, intracellular overexpression of PCSK9 results in decreased FFA uptake and utilization through a specific mechanism: PCSK9 competes with FFAs for binding to the CD36/FAT receptor and reduces their membrane recycling, resulting in an increase in systemic FFA levels and a significant reduction in fatty acid beta oxidation and the Krebs cycle ; this is the primary driver of atherosclerosis and cardiomyocyte injury processes. Moreover, it is conceivable that PCSK9 has a role in heart failure, hypertrophy, and cardiac fibrosis. These effects could be mediated by TNF-a and some chemokines; in fact, TNF-a upregulates PCSK9 gene expression via Peroxisome proliferator-activated receptors (PPARs) and PPAR gamma coactivator-1a (PGC1) pathways . 3. PCSK9i in Cardiovascular Outcome Trials Current guidelines of the American College of Cardiology and American Heart Association recommend the addition of non-statin cholesterol-lowering therapies for patients at very high risk of major adverse cardiovascular events (MACE) when LDL-C levels remain >= 70 mg/dL . About half of coronary heart disease patients on high-dose statin therapies reduce LDL-C less than 70 mg/dL . In this category of patients, there could be an additional clinical benefit deriving from the addition or substitution with other cholesterol-lowering agents, such as PCSK9 inhibitors, and this is a point of discussion in cardiology. Some randomized clinical trials have demonstrated how the administration of PCSK9 inhibitors, evolocumab, alirocumab, bococizumab, or inclisirian, as monotherapy or in combination with statins can reduce systemic levels of atherogenic and pro-inflammatory lipoproteins . Notably, PCSK9i significantly reduces LDL-C and up to 25% lipoprotein a (Lpa) . Effects on LPa levels are of particular interest in cardiology, considering its well established strong atherogenic, pro-inflammatory, and pro-thrombotic effects . A recent trial concluded that among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core) . This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis . The most known CVOT including PCSK9i are the FOURIER and ODYSSEY Outcomes trials. Patients with established cardiovascular disease or acute coronary syndrome (ACS) and elevated levels of LDL-C, non-high-density lipoprotein cholesterol, or apolipoprotein B were enrolled in these studies . Patients treated with PCSK9i reduced MACE, coronary heart disease, peripheral artery disease, and venous thromboembolic events. Some of these beneficial effects were also associated with LPa reductions . A brief description of the clinical benefits of each PCSK9i is provided below and summarized in Table 1:- Evolocumab Patients treated with evolocumab halved LDL cholesterol values . Furthermore, a recent meta-analysis showed that patients treated with evolocumab also had a slight but significant increase in HDL cholesterol; on the other hand, total cholesterol levels decreased by about 35-37% but with great heterogeneity of age and sex . Evolocumab was not effective in reducing triglyceride levels. Regarding adverse cardiac events, a recent meta-analysis showed that evolocumab reduced myocardial infarction by 27% and stroke by approximately 21% . A further interesting finding concerns unstable angina requiring revascularization which was reduced by 16% in patients treated with evolocumab vs. placebo. A further recent meta-analysis showed that evolocumab treatment reduces composite or CV death, myocardial infarction, stroke, and unstable angina by 15%. Moreover, in HUYGENS (High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study) study , evolocumab administration stabilized coronary plaque, resulting in regression of atheroma volume in patients with ACS. - Alirocumab Alirocumab is an additional PCSK9 inhibitor that has been extensively studied in cardiovascular outcome trials . A recent meta-analysis showed that patients treated with alorocumab increased HDL cholesterol levels by approximately 5% . Similarly to evolocumab, alirocumab reduces total cholesterol levels without affecting triglyceride levels. Furthermore, alirocumab, similarly to evolocumab, reduced composite of MI, stroke, unstable angina, and CV death. In a biweekly administered regimen, Alirocumab lower LDL-C by 45 to 60% depending on the applied dose (75 mg vs. 150 mg) and by ~ 50% while given monthly in a 300-mg dose . Moreover, we now have evidence that evolocumab and alirocumab treatment, on top of statins, in patients with ACS modifies coronary plaque properties, leading not only to a significant thickening of the fibrous cap, thereby stabilizing it, but also resulting in regression of atheroma volume in PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) study . - Bococizumab Bococizumab is an additional PCSK9 blocking monoclonal antibody which, unlike the other antibodies, has shown beneficial effects on MACE only in high-risk patients . Two large studies called SPIRE I and II enrolled more than 27,000 low-risk and high-risk patients (LDL 70 and 100 mg/dl, respectively) treated with bococizumab (150mg) twice a week. In SPIRE I , bococizumab showed no significant effects on composite of myocardial infarction, stroke, hospitalization for unstable angina requiring urgent revascularization, and cardiovascular death. IN SPIRE II, however, bococizumab reduced the primary endpoint of the SPIRE studies by 11%. However, a serious problem occurred in these patients, namely the production of antibodies to bococizumab, which resulted in very frequent injection site adverse reactions . - Inclisiran Inclisiran is a novel, small, interfering RNA aimed to target PCSK9 . In detail, the molecule is a modified double-stranded RNA conjugated to triantennary N-acetylgalactosamine (GalNAc). Liver cells are rich in the asialoglycoprotein receptor that binds to GalNAc, therefore, after subcutaneous administration, inclisiran accumulates significantly in the liver . Inclisiran lowered PCSK9 and LDL-C levels in a dose-dependent manner . After 2 doses of inclisiran, LDL-C was reduced by up to 53% at day 180 . Three large, randomized trials evaluated the cardiovascular efficacy of incisiran; these were called ORION 9-10 and 11 trials . In the ORION-9 trial, HeFH patients halved LDL cholesterol after approximately 500 days of treatment with inclisirian. In ORION 10 and 11, LDL cholesterol levels were reduced by approximately 52 and 49% over 500 days of treatment with inclisirian. Furthermore, in all trials, inclisirian also significantly reduced levels of total cholesterol, apolipoprotein B, triglycerides, and lipoprotein (a), thereby reducing many cardiovascular risk factors . Another cardiovascular outcome trial, currently underway, called ORION-4 (NCT03705234) , recruited 15,000 patients with ASCVD treated with inclisirian (300 mg) administered as a SC injection at randomization, (3 months and then every 6 months) or placebo aimed to evaluate any reductions in coronary heart disease (CHD) death; these were myocardial infarction, fatal or non-fatal ischemic stroke, or urgent coronary revascularization procedures . cancers-15-01397-t001_Table 1 Table 1 Main cardiovascular benefits derived from PCSK9i therapies in randomized controlled trials. Drug Chemistry Cardiovascular Benefits References Evolocumab Antibody - 50% reduction in LDL levels - 35-37% reduction in total cholesterol; increases in HDL levels - 27% reduction of myocardial infarction; 21% reduction of stroke - 15% reduction in composite or CV death, myocardial infarction, stroke, and unstable angina events - Stabilization of coronary plaque in patients with ACS Alirocumab Antibody - 5% increase in HDL levels - 45/60% reduction in LDL levels - Reduction in composite of MI, stroke, unstable angina, and CV death - Stabilization of atherosclerotic plaque and regression of atheroma volume in patients with MI Bococizumab Antibody - No significant effects on composite of MI, stroke, hospitalization for unstable angina requiring urgent revascularization, and cardiovascular death - 11% reduction in composite of MI, stroke, hospitalization for unstable angina requiring urgent revascularization, and cardiovascular death Inclisiran siRNA - 53% reduction in LDL levels - 52 and 49% reduction in LDL levels - Significant reduction of total cholesterol, Apolipoprotein-B, Triglycerides, and Lipoprotein (a) 4. PCSK9i in Oncology: Mechanisms and Potential Application Inhibitors of PCSK9 have been approved for the treatment of atherosclerotic cardiovascular diseases associated with hypercholesterolemia, however, a central role on immune tolerance in oncology has recently been investigated . Mechanistically, PCSK9 inhibits the recycling of major histocompatibility complex type I (MHCI) to the cell surface by promoting MHC I degradation . The inhibition of PCSK9 increases the expression of MHC I on the tumor cell surface, promoting intratumoral infiltration of cytotoxic lymphocytes . To be more detailed, PCSK9 directly interacts with amyloid precursor-like protein 2 (APLP2) which literally bridges MHC-I towards lysosomal degradation . All of this blocks MHC-I recycling by inducing peripheral immune tolerance. The same mechanism of promotion of lysosomal degradation by MHC-1 occurs for CD81, CD36, and the LDL receptor . Consequently, the use of PCSK9i can didactically create peripheral immune tolerance against tumor cells by optimizing recognition by T lymphocytes . Furthermore, the reduction of plasma levels of total cholesterol would lead to the inhibition of the ACAT-1 enzyme (deputy for cholesterol esterification) with further enhancement of the antitumor immune response . These data reveal that PCSK9 may be a crucial regulator for cancer immunotherapy. Inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase are the most important and studied pharmacological treatments aimed to decrease total cholesterol and LDL . For every 38.6 mg/dl reduction in LDL-C, ASCVD events are reduced by 21% after 1 year of treatment with high-intensity statin therapy. Recent RCTs have demonstrated that statin therapy combined with either ezetimibe or PCSK9 inhibitors reduces ASCVD events in high-risk populations . As described in introduction, treatment with ICIs reduce cancer-induced immune tolerance, providing significant improvements in survival and prognosis of cancer patients at different stages of the disease . PCSK9 is a new key player of cancer immune tolerance . Recently, it was demonstrated that PCSK9 regulates proliferation and apoptosis in human cancer cells . For example, in neuroglioma and NSCLC, knockdown of PCSK9 gene activates cancer apoptosis through caspase-3 and XIAP/p-Akt pathways . Another preclinical study in melanoma-bearing mice concluded that PCSK9 gene silencing significantly increases the response to ICIs . PCSK9 is also expressed and released by cancer cells . It was also reported that lowering blood cholesterol levels could boost cancer immunotherapy based on adoptive T cells . Cholesterol regulates the recycling of MHC I in cell membrane . PCSK9 blocking agents reduce systemic levels of total cholesterol and LDL, affecting the risk of atherosclerosis but also reducing the supply of cholesterol by cancer cells through the enhancement of apolipoprotein E receptor, CD36, b-secretase 1, and others . A study on colon cancer reveals that PCSK9 expression is upregulated in tumor cells compared with non-tumor cells and correlates with the degree of tumor invasiveness. Downregulation of the PCSK9 gene reduces colonic epithelial-to-mesenchymal transition, n-cadherin, and type 9 metalloproteases via the PI3K/AKT pathway. Furthermore, PCSK9 regulates the polarization of colonic peritumor macrophages, resulting in a pro-inflammatory and pro-metastatic phenotype . PCSK9 blocking agents could therefore be studied in patients with metastatic colon cancer. An association study of 14 lobular or ductal breast cancer patients found that systemic levels of PCSK9 are significantly higher in the advanced stage (stage III) than in patients with less aggressive disease stages and in benign lesions (p < 0.05). However, this study involved only a few dozen patients, so studies on a larger cohort of breast cancer patients should be conducted soon . A study of colon-bearing mice treated with PD-1 blocking agents found that treatment with immunotherapy increased tissue expression and systemic levels of PCSK9, CD36, and TGF-b . Combination of PCSK9 and PD-1 blocking agents in these models significantly increased the antitumor efficacy with strong synergism compared to monotherapies . The use of PCSK9 blocking agents increased the levels of pro-inflammatory and immune-stimulant cytokines, of intra-tumoral CD3+CD8+ lymphocytes, reducing CD4+, FOXP3+, CD25+ lymphocyte density. In liver cancer models, researchers demonstrated that PCSK9 is involved in resistance to VEGFR, PDGFR, and RAF kinases inhibitor sorafenib by direct inhibition of phosphatase and tensin homolog (PTEN) and consequent upregulation of the AKT pathway. In another study in colorectal cancel model, authors founded that PCSK9 induces oncogenesis in APC/KRAS mutant models of colon cancer and that systemic PCSK9 levels correlate with reduced survival in this patient cohort. PCSK9 blocking agents, especially when combined with statins, inhibit the neoplastic growth of APC/KRAS mutant colon cancer xenograft models by suppressing the KRAS/MEK/ERK pathway. Thus, the investigators conclude that PCSK9 inhibition may be a valid adjuvant therapy for APC/KRAS mutant colorectal cancer by suppression of the KRAS/MEK/ERK oncogenic pathway. A recent review summarizes that PCSK9 blocking agents are able to reduce prostate, lung, colon, and glioblastoma cancer cell growth through the induction of apoptosis, pyroptosis, and necrosis. Moreover, PCSK9 gene silencing reduces liver metastasis in melanoma-bearing mice through induction of intra-tumoral CD3+CD8+ lymphocytes levels . In another recent meta-analysis, patients with PCSK9 loss of function mutation have a lower odds of prostate cancer compared to non-mutant PCSK9 subjects . Another study on ovarian cancer models , evidenced that PCSK9 is also upregulated in ovarian cancer cells and correlated with tumor invasiveness by direct stimulation of ERK/MEK pathways. The use of PCSK9 blocking monoclonal antibodies or SiRNAs suppresses the growth of ovarian cancer cells by reducing AKT phosphorylation by reducing endogenous lipogenesis in these cells . A clinical study of non-small cell lung cancer patients has shown that low systemic levels of PCSK9 (<95 ng/mL) predict better responsiveness to the Programmed Death-1 (PD-1) Inhibitor Nivolumab and have better overall survival than patients with higher blood levels (>120 ng/mL) . In a recent biochemical study , an aptamer PL1 and Pcsk9 siRNA were able to potentiate anti PD-1/PD-L1 therapies in human colorectal cancer cells through enhancement of IFN-g and Granzyme B expression. A preclinical research study concluded that PCSK9 inhibition is able to increase major histocompatibility protein class I (MHC-I) membrane density on different cancer cells through the inhibition MHC-I lysosomal degradation, thereby increasing the concentration of intratumoral cytotoxic CD3+ CD8+ lymphocytes . 5. PCSK9 Inhibitors in Cardio-Oncology: A Potential Therapy in ASCVD Cancer Patients Treated with ICIs Immune-related adverse events (irAEs) seen in cancer patients treated with ICIs includes myocarditis, myositis, myasthenia gravis-like syndrome, endocrinophaties, and visceral obesity . Moreover, immune-related atherosclerotic vascular events (irAVEs) are also still associated with ICIs therapy in preclinical and clinical trials. In a recently published retrospective study, ICIs therapies increased atherosclerotic plaques volume through the involvement of immune-related inflammation pathways. Other ongoing prospective studies (NCT04586894, NCT03709771, NCT04115410) are aimed to demonstrate if ICIs therapies could increase AVEs events and potential mechanisms involved . However, in cardio-oncology, the reduction of several cardiovascular and cancer risk factors should be strictly considered. Among the best known cardio-oncological risk factors, we have the reduction of hyperglycemia, hypercholesterolemia, especially OX-LDL, triglycerides, homocysteine, insulin levels, hs-CRP, visceral fat, and smoking. Based on this, patients should be encouraged to follow a diet that complies with the European anti-cancer code and the WCRF directives, a non-sedentary lifestyle where possible (which is difficult especially in metastatic patients), and avoid smoking. However, PCSK9i-based drugs could be key cardioprotective strategies to reduce ASCVD in cancer patients treated with ICIs. Based on this, it is conceivable that a target population that could benefit from PCSK9 therapy are cancer patients treated with ICIs therapies, especially those with confirmed ASCVD. To this end, therefore, the benefits would be multiple: 1. enhancement of immunotherapy efficacy; 2. inhibition of mechanisms of resistance to apoptosis; 3. reduction of the risk of destabilization of stenotic plaque; 4. reduction of the risk of atherosclerosis induced by ICIs. To date, no studies have evaluated if PCSK9 blocking agents could reduce ASCVD in cancer patients treated with ICIs. A potential clinical trial could therefore include patients treated with ICIs in monotherapy or in combination with, for example, Ipilimumab, Nivolumab, Pembrolizumab, Durvalumab, Avelumab, or Atezolizumab. 6. Conclusions Inhibition of PCSK9 has emerged as a novel therapy to treat hypercholesterolemia and related cardiovascular diseases. Recent preclinical and clinical evidence supports the anticancer and immune-stimulating properties of PCSK9 inhibition therapy through the inhibition of peritumoral peripheral immune tolerance and reduction of cytokines involved in cancer cell survival. Cancer patients treated with ICIs in monotherapy or in an association therapy regimen have a three times greater risk of developing atherosclerotic plaques than patients not treated with ICIs and represent a population category that requires close pharmacological monitoring of atherosclerotic risk factors, including systemic inflammation, LDL, and OX-LDL levels. Cancer patients who develop ICIs-related ASCVD could benefit from PCSK9 inhibition therapy in order to reduce atherosclerotic events, cardiovascular mortality, and improve overall survival. Therefore, cardioprotective properties of PCSK9 inhibitors should be urgently explored in randomized clinical trials in patients with cancer at high risk of ASCVD. Author Contributions Conceptualization, V.Q. and N.M.; methodology, V.Q.; software, V.Q.; validation, N.M., A.I. and M.L.C.; formal analysis, M.I. and V.G.; investigation, C.M. and M.B.; resources, N.M.; data curation, M.L.C. and I.B.; writing--original draft preparation, V.Q.; writing--review and editing, V.Q. and N.M.; visualization, A.I.; supervision, N.M. and A.P.; project administration, M.I.; funding acquisition, N.M. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Cancer patients treated with ICIs therapies (i.e., PD-1 or PDL-1 or CTLA-4 blocking agents or OX40 agonists) increases endothelial DAMPs, including Galectine-3, cytokines, chemokines, growth factors, and hs-CRP that are associated with plaque progression and instability. Figure 2 PCSK9 chemical structure. The structure of PCSK9 reveals four major components in the pre-processed protein: the signal peptide (residues 1-30); the N-terminal pro-domain (residues 31-152); the catalytic domain (residues 153-425); and the C-terminal domain (residues 426-692), which is further divided into three modules. Figure 3 PCSK9 role in cancer immune-recognition. PCSK9 induces lysosomal degradation of MHC-I after binding to a cancer antigen, thus reducing cancer membrane MHC-I density, making the tumor cell immune-irresponsive (peripheral immune tolerance). When PCSK9 is blocked by monoclonal antibodies, MHC-I is recycled after binding to a cancer antigen, therefore allowing the recognition of the MHC-I-Antigen complex by the TCR (signal 1) which, thanks to the type 2 signal (CD28-CD8 binding), allows the activation, proliferation, and survival of the T lymphocyte and the consequent rupture of the peripheral immune tolerance. 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PMC10000233 | Recently, circulating microRNAs (miRNAs) have emerged as potential non-invasive biomarkers for breast cancer (BC) management. In the context of BC patients undergoing neoadjuvant chemotherapy (NAC), the possibility of obtaining repeated, non-invasive biological samples from patients before, during, and after treatment is incredibly convenient and provides the opportunity to investigate circulating miRNAs as diagnostic, predictive, and prognostic tools. The present review aims to summarize major findings in this setting, thus highlighting their potential applicability in daily clinical practice and their possible limitations. In all the contexts (diagnostic, predictive, and prognostic), circulating miR-21-5p and miR-34a-5p have emerged as the most promising non-invasive biomarkers for BC patients undergoing NAC. Specifically, their high baseline level could discriminate between BC patients and healthy controls. On the other hand, in predictive and prognostic investigations, low circulating miR-21-5p and miR-34a-5p levels may identify patients with better outcomes, in terms of both treatment response and invasive disease-free survival. However, the findings in this field have been very heterogeneous. Indeed, pre-analytical and analytical variables, as well as factors related to patients, may explain the inconsistency among different study results. Thus, further clinical trials, with more precise patient inclusion criteria and more standardized methodological approaches, are definitely needed to better define the potential role of these promising non-invasive biomarkers. microRNAs circulating miRNAs breast cancer neoadjuvant chemotherapy pathological complete response This research received no external funding. pmc1. Introduction Breast cancer (BC) is the most prevalent neoplasm and the leading cause of cancer-related mortality among women globally, although improvements in early diagnostic procedures and advances in treatments have contributed to decreasing the mortality rate over time . Pathological variables such as tumor grade (G), TNM stage, proliferation index (Ki67), hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression, and molecular subtype are well-known features that strongly influence patients' prognoses. Together with clinical (e.g., menopausal status, age, and performance status) and biological (e.g., genomic signature) parameters, these pathological features are essential for the identification of the best-tailored treatment. In BC management, neoadjuvant chemotherapy (NAC) is a well-established therapeutic choice for selected high-risk early and locally advanced BC . However, before starting treatment, the individual response to NAC and the subsequent long-term prognosis has been almost unpredictable to date. Likewise, an early identification of patients with poor tumor response could be crucial for avoiding unnecessary treatments and related side effects. For this reason, there is an urgent clinical need for non-invasive prognostic/predictive biomarkers in the neoadjuvant setting. A biomarker is considered prognostic if it provides information about outcomes regardless of treatment, reflecting the underlying intrinsic behavior of the disease, whereas a biomarker is considered predictive if treatment outcomes are different for biomarker-positive patients compared to biomarker-negative patients . MicroRNAs (miRNAs) are highly conserved small noncoding RNAs formed by approximately 22 nucleotides which play key roles in gene regulatory networks. MiRNA biogenesis is a complex process involving several enzymes that first generate a primary miRNA, then a precursor miRNA (pre-miRNA) and finally a miRNA duplex composed of two strands: the 5p and the 3p (generating from the 5' end and 3' end of the pre-miRNA, respectively) . One of the strands (the guide strand) is then loaded into the Argonaute (AGO) family of proteins, generating the miRNA-induced silencing complex (miRISC) that is able to bind transcripts, thus leading to mRNA degradation, translational suppression, or, as has been more recently discovered, an increase in the translation of target mRNA . The other strand (the passenger strand) was initially thought to be degraded; however, it has been demonstrated that both strands can be incorporated into the miRISC complex depending on tissue or cell type . The miRBase database (a searchable database of published miRNA sequences and annotations) provides information on stem-loop and mature miRNA sequences, including which is the guide strand (for which the miRBase alias is the miRNA name without any specification: miR) and which is the passenger ones (also named star strand; miRBase alias: miR*). Thus, the lack of specific information about the miRNA strand under investigation in a research paper means that the authors refer to the miRBase alias used for the guide strand. However, for a few miRNAs (e.g., miR-718, -4516, -422a, -484), it has not yet been defined in the miRBase which is the guide strand. The discovery that miRNAs are differently expressed in normal tissue and several tumor types, including BC , has generated a great deal of interest in the scientific community. To date, miRNA signatures from normal tissues, cancer tissues, and metastases have been used to classify different types of cancer and have been shown to represent potential biomarkers for diagnosis, prognosis, and treatment response . In addition, different studies have shown that miRNAs can be released from cells and enter circulation . In fact, it has been demonstrated that miRNAs can be found in circulation as a passive consequence of apoptotic and necrotic cell death, or due to active secretion through regulated cellular processes . As a result, these molecules have also been found in several human bodily fluids (including blood, serum, plasma, urine, saliva, seminal fluid, and pleural effusion) , in a stable form protected from endogenous RNAses (i.e., in vesicles such as exosomes, microvesicles, and apoptotic bodies, or associated with proteins such as AGO2), thus making circulating miRNA levels well suited for non-invasive analysis in patient samples . Indeed, independent studies have reported the feasibility of using circulating miRNAs as potential disease biomarkers of tumor clinical-pathological variables and patient clinical outcomes, including for BC . In the context of NAC for early BC, the availability of non-invasive biological samples before, during, and after treatment is strongly convenient and provides the opportunity to investigate circulating miRNAs as prognostic and predictive biomarkers for daily clinical practice. This review aims to summarize the major findings regarding circulating miRNAs as diagnostic, predictive, and prognostic biomarkers in BC patients undergoing NAC, by highlighting their potential applicability in clinical practice and their possible limitations. 2. Diagnostic Potential of Circulating miRNAs In recent decades, several studies have thoroughly investigated circulating miRNAs as candidates for discriminating between BC patients and healthy controls, and possibly contributing to BC diagnosis in the case of incertitude. As reported in Table 1, the results of these case-control studies have been very heterogeneous and somewhat conflicting. The miRNAs most frequently cited in the literature for their potential diagnostic value are miR-21-5p and miR-155-5p (oncogene-like), and miR-let-7a-5p and miR-34a-5p (tumor suppressor-like). Strong and consistent data from multiple studies have shown that circulating miR-21-5p levels were significantly higher in the serum and plasma of BC patients compared to healthy women, regardless of subtypes . In addition, Rodriguez-Martinez et al. reported significantly higher miR-21-5p levels in advanced BC patients compared to early BC, suggesting that circulating miR-21-5p may be a promising candidate not only for early tumor detection but also as a marker of tumor burden . Similarly, the analyses of circulating miR-155-5p levels showed highly consistent results across studies, indicating a marked increase in serum miRNA levels in BC patients compared to healthy controls . In contrast, for the tumor suppressor-like miRNAs miR-let-7a-5p and miR-34a-5p inconsistent results have been reported among different studies. In fact, Marques et al. reported markedly lower levels of miR-let-7a-5p in plasma and serum samples from BC patients compared to healthy controls . However, in other studies significantly higher levels of miR-let-7a-5p were found in blood or serum of BC patients compared to healthy individuals . Similarly, circulating miR-34a-5p levels were significantly higher in BC women compared to healthy volunteers in several studies but, in the case-control series reported by Freres et al., the authors found opposing results . As part of diagnostic evaluation, many studies then analyzed the possible correlation among circulating miRNA levels and some of the key BC clinical-pathological features . The strongest evidence concerns tumor grade, tumor size (T), lymph node involvement, clinical stage, molecular subtypes, HR, and HER2 expression. Several miRNAs have been associated with tumor grade in different studies. In particular, serum miR-125b-5p levels were significantly increased in high pathologic grade compared to low-grade tumors in a series of Luminal B patients . Similarly, serum miR-155-5p, plasma miR-21-5p, and blood miR-195-5p levels were higher in G3 than in G2 tumors . Serum levels of miR-21-3p, miR-10b-3p, miR-145-3p, and miR-let-7a-3p were shown to correlate directly with T stage: higher levels were associated with higher tumor size . In addition, serum miR-21-5p and miR-34a-5p levels were significantly higher in T3-T4 stages compared to T1-T2 in BC patients. Similar results were observed by Heneghan et al., who reported a significant increase in the circulating levels of miR-195-5p in blood samples of BC patients with T3-T4 tumors compared to T1-T2 ones . Moreover, Stevic et al. reported that the plasma levels of six miRNAs (-185-5p, -376a-3p, -382-5p, -410-3p, -433-3p, and -628-5p) were significantly associated with a higher tumor stage (i.e., T3-T4 versus T1-T2) in a cohort of HER2-positive BC patients . Across different studies, several circulating miRNAs have been investigated in early BC patients in association with nodal involvement. Increased levels of circulating miR-210-3p in plasma and miR-125b-5p and miR-21-5p in serum directly correlated with the positivity of locoregional nodes. However, several other miRNAs in plasma (-24-3p, -92a-3p, -143-3p, -146-5p, -185-5p, -193b-3p, and -484) and serum (-155-5p , -182-5p , and -3200-3p ) have been found to be inversely related to nodal status, with lower levels found in patients with nodal involvement. Multiple circulating miRNAs were also assessed for their possible relationship with clinical stage. Among them, miR-21-5p , miR-155-5p , miR-182-5p , miR-373-3p , miR-221-3p , miR-125b-5p , and miR-10b-5p had significantly higher levels in both the serum and plasma of BC patients in advanced clinical stages compared to earlier stages (i.e., II versus III, or I-II versus III-IV). Several circulating miRNAs were found to have different levels depending on the BC molecular subtype. Serum circulating miR-200c-3p levels were lower in triple-negative breast cancer (TNBC) patients compared to estrogen receptor (ER)- and progesterone receptor (PgR)-positive BC patients . Conversely, Luminal-like tumors showed lower plasma miR-185-5p levels compared to TNBC . Finally, Rodriguez-Martinez et al. reported definite level profiles of miRNA-222-3p in serum samples according to molecular subtype: it was decreased in Luminal A compared to basal-like and Luminal B tumors . A large number of circulating miRNAs were investigated in relation to ER status. Indeed, high levels of circulating miR-221-3p in serum and miR-185-5p and miR-34a-5p in plasma were associated with the negative expression of both ER and PgR. Correlation among circulating miRNAs and ER was also observed for miR-195-5p (in blood samples) , miR-let-7a-5p , and miR-145-5p (in plasma samples), with higher levels directly related to higher ER expression. In addition to the aforementioned results, circulating miR-221-3p, miR-185-5p, and miR-34a-5p, and serum miR-21-5p were also found to be inversely correlated with ER positivity (i.e., low circulating levels were related to higher ER expression) in a study conducted by Al-Khanbashi M and colleagues . Concerning PgR expression, serum miR-222-3p and miR-10b-5p showed an inverse association with PgR positivity, with higher levels mostly found in PgR-negative BC. Finally, regarding HER2 status, Zhang et al. identified three circulating miRNAs that were significantly associated with HER2 expression: serum levels of miR-375-3p, miR-718, and miR-4516 were lower in patients with HER2-negative tumors than in those with HER2-positive BC . Moreover, higher plasmatic levels of miR-24-3p and miR-185-5p were associated with HER2-positive tumors . Currently, there are no data on the correlation between circulating miRNA levels and low HER2 status (i.e., tumors expressing HER2 protein at the 1+ or 2+ immunohistochemistry level without HER2 gene amplification). cancers-15-01410-t001_Table 1 Table 1 Circulating miRNAs with a potential diagnostic role in differentiating between BC patients and healthy controls, BC molecular subtypes, and disease stage. miRNA Sample BC Patients/ Healthy Controls BC Subtype Method Findings Ref 10b-3p Plasma 30/20 All qRT-PCR higher levels in BC vs. HC 10b-5p Serum 56/10 All qRT-PCR higher levels in BC vs. HC Serum 89/29 All qRT-PCR higher levels in advanced BC vs. HC 15a-5p Serum 8/20 TNBC qRT-PCR lower levels in TNBC vs. HC 17-5p Serum 8/20 TNBC qRT-PCR lower levels in TNBC vs. HC 18a-5p Serum 8/20 TNBC qRT-PCR lower levels in TNBC vs. HC 19a-3p Serum 118/30 -PCR higher levels in BC vs. HC 19b-3p Serum 16/20 All qRT-PCR lower levels in TNBC vs. HC 21-3p Plasma 30/20 All qRT-PCR higher levels in BC vs. HC 21-5p Serum 53/8 Not specified qRT-PCR higher levels in BC vs. HC higher levels in advanced BC vs. early BC Serum 8/20 All qRT-PCR higher levels in TNBC vs. HC Serum 127/19 HER2+ qRT-PCR higher levels in BC vs. HC Plasma 29/28 HER2+ qRT-PCR higher levels in BC vs. HC Serum 118/30 -PCR higher levels in BC vs. HC Serum 75/75 Not specified qRT-PCR higher levels in BC vs. HC 27a-3p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in BC vs. HC lower levels in TBNC vs. HER2 27b-3p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in BC vs. HC lower levels in TBNC vs. HER2 29a-3p Plasma 29/28 HER2+ qRT-PCR higher levels in BC vs. HC 29c-3p Serum 76/52 All qRT-PCR higher levels in BC vs. HC 30b-5p Serum 16/20 All qRT-PCR lower levels in TNBC vs. HC 34a-5p Serum 39/10 All qRT-PCR higher levels in BC vs. HC Plasma 59/20 All qRT-PCR lower levels in BC vs. HC Serum 86/20 -PCR higher levels in BC vs. HC Serum 89/29 All qRT-PCR higher levels in advanced BC vs. HC 105-5p Serum 53/8 Not specified qRT-PCR higher levels in BC vs. HC 122-5p Plasma 59/20 All qRT-PCR higher levels in BC vs. HC 125b-5p Serum 118/30 -PCR higher levels in BC vs. HC 126-3p Plasma 29/28 HER2+ qRT-PCR higher levels in BC vs. HC 145-3p Plasma 30/20 All qRT-PCR lower levels in BC vs. HC 155-5p Serum 56/10 All qRT-PCR higher levels in BC vs. HC Serum 118/30 -PCR higher levels in BC vs. HC Serum 89/20 All qRT-PCR higher levels in BC vs. HC 181a-3p Plasma 30/20 All qRT-PCR higher levels in BC vs. HC 195-5p Serum 210/102 All qRT-PCR lower levels in BC vs. HC Blood 83/63 Not specified qRT-PCR higher levels in BC vs. HC Serum 72/72 All qRT-PCR lower levels in BC vs. HC 199a-5p Serum 76/52 All qRT-PCR higher levels in BC vs. HC 205-5p Serum 118/30 -PCR higher levels in BC vs. HC 210-3p Serum 127/19 HER2+ qRT-PCR higher levels in BC vs. HC Plasma 29/28 HER2+ qRT-PCR higher levels in BC vs. HC 221-3p Plasma 93/32 All qRT-PCR higher levels in BC vs. HC 335-5p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in TNBC vs. HC higher levels in TNBC vs. HER2+ 365a-3p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in HER2+ BC vs. HC lower levels in TNBC vs. HER2+ 376c-3p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in TNBC vs. HC higher levels in TNBC vs. HER2+ 373-3p Serum 127/19 HER2+ qRT-PCR higher levels in BC vs. HC Serum 118/30 -PCR higher levels in BC vs. HC 382-5p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in TNBC vs. HC higher levels in TNBC vs. HER2+ 422a Plasma 435/20 HER2+ and TNBC qRT-PCR lower levels in HER2+ BC vs. HC higher levels in TNBC vs. HER2+ 424-5p Serum 76/52 All qRT-PCR higher levels in BC vs. HC 433-3p Plasma 435/20 HER2+ and TNBC qRT-PCR higher levels in TNBC vs. HC higher levels in TNBC vs. HER2+ 451-5p Serum 118/30 -PCR lower levels in BC vs. HC 628-5p Plasma 435/20 HER2+ and TNBC qRT-PCR lower levels in HER2+ vs. HC higher levels in TBNC vs. HER2+ let-7a-5p Serum 8/20 TNBC qRT-PCR higher levels in TNBC vs. HC Serum 72/72 All qRT-PCR lower levels in BC vs. HC Blood 83/63 Not specified qRT-PCR higher levels in BC vs. HC let-7a-3p Plasma 30/20 All qRT-PCR lower levels in BC vs. HC let-7e-5p Serum 8/20 TNBC qRT-PCR higher levels in TNBC vs. HC Abbreviations: BC: breast cancer; HC: healthy control; HER2: human epidermial growth factor 2; TNBC: triple-negative breast cancer; qRT-PCR: quantitative real-time polymerase chain reaction; Ref: reference. 3. Predictive Potential of Circulating miRNAs For the prediction of clinical and pathological outcomes in an NAC setting, a plethora of circulating miRNAs have been investigated (Table 2). Here, we report the most extensively researched ones, underlining their potential clinical relevance. Among them, miR-21-5p has emerged as an independent predictor of response in several studies. In fact, low levels of circulating miR-21-5p before NAC (based on paclitaxel and doxorubicin) have been associated with a higher likelihood of favorable response to NAC in HR-positive BC patients . Similarly, in a multicentric prospective study by McGuire and colleagues, which assessed a predefined panel of circulating miRNAs (selected on their reported relevance in BC) as a measure of NAC response in all BC subtypes, the whole-blood miR-21-5p levels of responders (defined as patients who had a complete response or >90% reduction in primary T) were considerably lower than those of non-responders (defined as patients with <90% reduction in primary T) in the HR-positive subtype (p = 0.048). On the contrary, in TNBC and HER2-positive BC, the response to NAC was not associated with circulating levels of miR-21-5p . Likewise, similar results were reported in a Ukrainian retrospective study, which included 182 patients with stage II-III HR-positive/HER2-negative BC undergoing NAC with polychemotherapy with fluorouracil, doxorubicin, and cyclophosphamide or doxorubicin/cyclophosphamide. Patients with chemo-sensitive tumors (evaluation of NAC response performed every two cycles by mammography) showed changing in serum baseline levels of miR-21-5p lower than two-fold, while those with resistant tumors had a change above three-fold . In the same study, serum miR-205-5p levels increased more than four-fold in chemotherapy-sensitive patients with the HR-positive/HER2-negative subtype and decreased lower than 2.5-fold in patients with a poorer response . In contrast, another observational study with a similar cohort of patients (68 luminal A stage II-III BC patients for the discovery group, and 56 patients for the validation one) revealed that serum miR-205-5p levels in patients undergoing paclitaxel-based NAC were higher in the resistant group (defined as no or minor reduction (<=30%)) compared to the sensitive group (defined as a decrease of >30% or no residual invasive cancer; p < 0.05) . Besides miR-21-5p and miR-205-5p, miR-375-3p has also been shown to be a promising predictive biomarker whose basal levels are associated with response. Zhang et al. prospectively investigated the role of several miRNAs in 37 luminal B BC patients undergoing NAC with /or anthracycline-based regimens, plus trastuzumab for HER2-positive cases. In luminal B HER2-negative patients, relatively low baseline serum levels of miR-375-3p were found to be associated with pathological complete response (pCR) (p = 0.043) and "comprehensive response", defined as partial or complete response in clinical evaluation and loss > 30% or no residual invasive cancer in pathological evaluation (p = 0.023) . Similar results were observed in the luminal A subtype in the abovementioned Ukrainian study, where decreased baseline levels predicted sensitivity to NAC with fluorouracil, doxorubicin, and cyclophosphamide, or doxorubicin and cyclophosphamide . On the contrary, in the study by Wu and colleagues, when applying de novo sequencing to identify circulating miRNAs associated with BC clinical outcome, lower levels of miR-375-3p significantly correlated with not achieving pCR in HER2-positive BC patients receiving doxorubicin/cyclophosphamide treatment followed by carboplatin and nab-paclitaxel plus trastuzumab . Multiple studies are concordant on the possible association between circulating miR-125b-5p and NAC response. In fact, circulating baseline levels of miR-125b-5p were found to be higher in non-responders (defined as stable or progressive disease) compared to responders (defined as partial or complete response; p = 0.008) in serum samples of 56 BC patients with invasive ductal carcinoma undergoing four to six cycles of NAC with 5-fluorouracil, epirubucin, and cyclophosphamide . Similarly, a Chinese study involving 118 patients diagnosed with stage II/III BC and undergoing four to six cycles of NAC with docetaxel, epirubicine, and cyclophosphamide showed that significantly higher levels of serum miR125b-5p were present in patients who had stable or progressive disease compared to those that had reached partial or complete response . The identification of biomarkers that can be repeatedly tested through non-invasive approaches could provide the possibility of analyzing real-time information on disease evolution during treatment (Table 3). In this context, many studies have aimed to identify the predictive biomarkers of NAC response by monitoring miRNA dynamic changes on multiple blood samples collected during therapy. Again, one of the most investigated circulating miRNAs is miR-21-5p. A prospective clinical trial by Davey MG et al. evaluated the possible role of circulating miRNAs in decision making for NAC . Blood miRNA levels were measured at diagnosis (Timepoint 1, or T1), and after two cycles of NAC (T2) in a total of 120 patients (59 luminal A, 21 luminal B, 15 HER2-positive, 25 TNBC). In the overall cohort, no circulating miRNAs were associated with response to NAC, but decreased or increased miR-21-5p levels trended to significance as associated with treatment response in specific BC subtypes. A second analysis evaluated levels of serum miRNAs during NAC in 83 HER2-positive early BC patients treated with four to six cycles of taxane-carboplatin plus trastuzumab . Serum samples were collected before treatment, at the end of the second cycle, and at the end of therapy. The results showed that serum miR-21-5p levels in clinical responders were significantly lower at the end of the second cycle and at the end of therapy compared to baseline level (p < 0.001 for both), while there was no significant difference in non-responders. Dynamic circulating miR-21-5p levels were also investigated by Liu B. et al. in 118 patients affected by early HER2-negative BC receiving four to six cycles of NAC with an association of docetaxel, epirubicin, and cyclophosphamide (TEC regimen). Blood samples were collected before treatment, at the end of the second cycle, and at the end of NAC. In line with the abovementioned results, the mean miR-21-5p level was lower during and after NAC than at baseline in responders (p = 0.016 for both), but not in non-responders. These results suggested that a decreased level of serum miR-21-5p detected after the second NAC cycle (compared to baseline) could be able to predict responder patients. Besides miR-21-5p, other circulating miRNAs have been investigated for their dynamic changes during NAC. The abovementioned prospective trial performed by Zhang Z. et al. evaluated circulating miRNAs in 37 luminal B early BC patients . Blood samples were collected at baseline, and after two/four cycles of NAC. The circulating miR-210-3p levels during NAC were increased in non-responders, while the authors did not find a significant change in responders. In addition, significantly higher plasma miR-210-3p levels were observed in the non-pCR group than in the pCR group. Circulating levels of miR-210-3p associated with sensitivity to trastuzumab were evaluated in another trial involving 29 patients with HER2-positive early BC . Patients received four cycles of taxanes followed by four cycles of anthracycline-based chemotherapy plus trastuzumab. Plasma samples were collected preoperatively and in the second postoperative week. The mean baseline level of plasma miR-210-3p was higher in samples from patients with residual disease than in the pCR group (p = 0.0359). In the above-mentioned study by Liu B. et al. analyzing the dynamic predictive role of circulating miR-125b-5p , a significant association was found between miRNA level and NAC response; miR-125b-5p level was higher at all timepoints in non-responders than in responders; however, treatment did not induce statistically significant changes in miRNA levels in either group. Moreover, the analysis by Zhang Z. et al. reported that, in the luminal B/HER2-positive cohort, the levels of circulating miR-125b-5p remained relatively stable from the baseline through the first two/four cycles of NAC, in patients with both complete and partial response . Recently, Todorova K. et al. performed RNA sequencing on plasma samples collected from 20 BC patients before and after the first cycle of NAC (combination of doxorubicin with cyclophosphamide). The authors showed an increased level of circulating miR-34a-5p after the first NAC dose in patients that did not achieve pCR . Similarly, another analysis reported that the miR-34a-5p levels were significantly increased after two/four cycles of NAC (compared to baseline level) in luminal B responder patients, regardless of HER2 status . A further study investigated serum miR-34a-5p levels during NAC in 86 HER2-negative BC patients . All patients received six cycles of chemotherapy (anthracycline plus taxane-based regimen). Serum samples were collected at baseline, at the end of the second cycle, and at the end of NAC. The authors found that changes in miR-34a-5p levels during NAC were significantly associated with the chemotherapeutic responses. At the end of the second cycle and at the end of NAC, almost all responders had decreased serum miR-34a-5p levels compared to baseline (p < 0.001 for both). Finally, Zhu W. et al. evaluated the dynamics of circulating miR-34a-5p during NAC (i.e., epirubicin-paclitaxel regimen) . In the HER2-positive and TNBC cohorts, plasma miR-34a-5p levels were significantly decreased in chemo-insensitive patients after the first two cycles of NAC (p = 0.027 and p = 0.006, respectively), while they remained stable throughout the course of treatment in chemo-sensitive patients (no statistically significant changes). In an analysis by Davey G.M. et al. , the authors found that increased miR-let-7a-5p levels (from baseline to after the second cycle of NAC) identified patients who achieved partial or complete response in the luminal HER2-positive cohort (p = 0.049), whereas in the luminal cohort reduced miR-let-7a-5p levels predicted achieving pCR (p = 0.037). Circulating miR-let-7a-5p was also analyzed in the NEOCENT trial, a phase III translational study in which 63 patients (ER-rich) were randomized 1:1 to receive chemotherapy (anthracycline-based regimen, followed by docetaxel in the case of poor response after the first three cycles) or endocrine therapy (letrozole) . Blood samples were collected at baseline, after 8 weeks, shortly before surgery, and 6-monthly for 2 years; miRNA markers were assessed from baseline to the end of treatment for both arms. An increase in circulating miR-let-7a-5p level was associated with objective radiological response in both arms, but it was statistically significant only in the chemotherapy arm (p = 0.008). cancers-15-01410-t002_Table 2 Table 2 Main findings on circulating miRNAs as predictive markers in BC patients undergoing NAC. miRNA Sample BC Patients BC Subtype Method Predictive Findings Ref 21-5p Whole blood 114 All qRT-PCR Independent predictor of responseIn HR+, reduced levels in responders vs. non responders Plasma 72 HR+ q-PCR Independent predictive factor of MP response to neoadjuvant chemotherapyReduced levels in responders vs. non-responders Serum 182 HR+, HER2+ qRT-PCR Reduced levels correlated with sensitivity to NACIncreased levels correlated with resistance to NAC 145-5p Whole blood 120 All qRT-PCR In +, lower levels predicted achievement of pCR (p = 0.027) Whole blood 114 All qRT-PCR In HR+, significantly lower levels in responders vs. non-responders (p = 0.033) 205-5p Serum 182 HR+, HER2+ qRT-PCR In HR+, increased levels predicted sensitivity to NACIn HER2+, low levels predicted resistance to NAC Serum 68 HR+ RT-PCR Increased levels predicted resistance to NAC based on epirubicin plus paclitaxel (p = 0.003) 210-3p Serum 37 Luminal B qRT-PCR Increased levels in pathological responders vs. non-responders (OR = 0.07, 95% CI = 0.01-0.45, p = 0.01) Plasma 29 HER2+ RT-PCR Increased levels in residual disease vs. pCR (p = 0.0359) 222-3p Plasma 109 All qRT-PCR In HR+ HER2-, upregulation predicted response to NAC (OR = 6.422, p = 0.049) Serum 65 HER2+ qRT-PCR Reduced levels predictors of pCR (OR = 0.258, p = 0.043) 375-3p Serum 37 Luminal B qRT-PCR In HER2-, lower levels predicted in pCR Serum 182 HR+, HER2+ qRT-PCR In HR+, reduced levels predicted sensitivity to NAC Serum 42 All qRT-PCR In HER2+, high levels predicted resistance to NAC 19a-3p Serum 68 HR+ RT-PCR Increased levels predicted resistance to NAC-based on epirubicin plus paclitaxel 19b-3p Serum 8 TNBC RT-PCR In TNBC, higher levels in no cCR to NAC 30b-5p Plasma 20 HR+, TNBC NGS Upregulation predicted pCR Serum 8 TNBC RT-PCR In TNBC, higher levels in no cCR to NAC 34a-5p Plasma 39 All qRT-PCR Higher levels in PD vs. SD/PR/CR (p = 0.03) 423-5p Plasma 20 HR+, TNBC NGS Downregulation predicted pCR (p = 0.0005) 718 Serum 37 Luminal B qRT-PCR Lower levels in clinical responders vs. non responders (p = 0.031) 4516 Serum 37 Luminal B qRT-PCR Lower levels in clinical responders vs. non responders (p = 0.016) 146a-5p Plasma 72 HR+ q-PCR Independent predictive factor of MP response to neoadjuvant chemotherapyReduced levels predictors of response 26a-5p Plasma 72 HR+ q-PCR Independent predictive factor of MP response to neoadjuvant chemotherapyReduced levels predictors of response 127-3p Plasma 20 HR+, TNBC NGS In TNBC, upregulation strongly predictor factor of pCR 195-5p Whole blood 114 All qRT-PCR Reduced levels in responders vs. non responders 221-3p Plasma 93 All RT-PCR Independent factor for chemoresistance 328-3p Plasma 20 HR+, TNBC NGS Downregulation predicted pCR (p = 0.0019) 125b-5p Serum 56 All qRT-PCR Higher levels in non-responders vs. responders (p = 0.008) BC: breast cancer; cCR, clinical complete response; HER2: human epidermial growth factor 2; MP: Miller-Payne; HR: hormone receptor; NAC: neoadjuvant chemotherapy; NGS: next-generation sequence; OR: odd ratio; qRT-PCR: quantitative real-time polymerase chain reaction; pCR: pathological complete response; PD: progression disease; PR: partial response; SD: stable disease; Ref: reference. cancers-15-01410-t003_Table 3 Table 3 Statistically significant dynamic changes in circulating miRNA levels in BC patients undergoing NAC and association with response to treatment (p < 0.05). Up arrow indicates increased level from baseline. Down arrow indicates decreased level from baseline. Responders Non-Responders miRNA BC Subtype After 1-4 Cycles of NAC At the End of NAC After 1-4 Cycles of NAC At the End of NAC Ref 21-5p HER2+ | | HER2- | | 145-5p All | in HER2+ 210-3p HER2+ | 222-3p Not specified | in HR+/HER2- 34a-5p HER2- | | All | in HER2+ | in TNBC | in HER2+ let-7a-5p All | in HR+ HER2+ | Luminal Abbreviations: BC: breast cancer; HER2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer; HR: hormone receptor; NAC: neoadjuvant chemotherapy; Ref: reference. 4. Prognostic Potential of Circulating miRNAs MiRNAs have been extensively investigated for their promising role as prognostic biomarkers. However, despite several analyses suggesting them as potential prognostic tools in BC, the clinical application of these findings has yet to be verified . A recent meta-analysis by Zhang et al. analyzed 39 miRNAs with a prognostic value from 23 studies and found that 26 miRNAs were associated with survival outcomes. Although the study did not distinguish between tissue and circulating miRNAs, they identified miR-125b-5p, miR-21-5p, and miR-7-5p as the most frequently investigated ones with significant results. After reviewing the most recent literature, we identified seven circulating miRNAs significantly associated with prognosis in BC patients treated with NAC (Table 4). cancers-15-01410-t004_Table 4 Table 4 Main findings on circulating miRNAs as prognostic markers in BC patients undergoing NAC. miRNA Sample BC Patients/ Healthy Controls BC Subtype Method Prognostic Findings Ref 21-5p Serum 127/19 HER2+ qRT-PCR Increased levels of circulating miR-21 before (p = 0.0091) and after (p = 0.037) NAC with trastuzumab and lapatinib showed a significant association with poor OS Serum 118/30 -PCR Decreased expression from BL to FEN and from BL to SEN during NAC had better DFS (p < 0.001) Serum, blood 83/30 HER2+ qRT-PCR Decreased serum expression from BL to the end of the second cycle and from BL to the end of NAC with trastuzumab correlated with better OS and DFS (p < 0.001) Serum 326/223 Not specified qRT-PCR High serum levels correlated with shorter RFS (p = 0.026) and DFS (p = 0.0033) Serum 75 Not specified qRT-PCR Increased expression (>nine-fold) was significantly associated with poor survival (p = 0.002) 34a-5p Serum 86/20 -PCR Decreased expression from the end of second cycle and the end of NAC to before NAC correlated with better DFS (p < 0.001) Blood 20 HR+, TNBC NGS Low level was prognostic for survival (p = 0.19) 125b-5p Serum 118/30 -PCR Lower expression at BL, FEN and SEN correlated with more favorable DFS (p < 0.001) 375-3p Serum 182 HR+, HER2+ qRT-PCR Low serum level (<0.15) correlated with lower 3-y RFS in luminal B patients 222-3p Serum 65 HER2+ qRT-PCR Low serum expression correlated with better DFS (p = 0.029) and OS (p = 0.0037) 4515p Serum 27/36 Not specified qRT-PCR High levels at the time of diagnosis were associated with better DFS (p = 0.046) 182-5p Serum 182 HR+, HER2+ qRT-PCR High serum level (>5.5) correlated with lower 3-y RFS in luminal A patients Abbreviations: BC: breast cancer; BL: baseline; DFS: disease-free survival; FEN: first evaluation during neoadjuvant chemotherapy; HER2: human epidermal growth factor 2; HR: hormone receptor; NAC: neoadjuvant chemotherapy; NGS: next-generation sequence; OS: overall survival; qRT-PCR: quantitative real-time polymerase chain reaction; RFS: recurrence free survival; SEN: second evaluation during neoadjuvant chemotherapy; Ref: reference. As for diagnosis and prediction, among prognostic miRNAs, circulating miR-21-5p is one of the most extensively studied with the most robust data . There is consistent evidence that low circulating miR-21-5p levels are associated with better outcomes, while higher levels are associated with worse outcomes. A study by Muller et al. was the first to investigate the effects of NAC with trastuzumab and lapatinib on serum levels of circulating miR-21-5p, miR-210-3p, and miR-373-3p in 129 HER2-positive BC patients compared with a cohort of 19 healthy controls. One of the aims of the study was to evaluate whether specific miRNA levels were associated with prognosis. Of the miRNAs investigated, only increased levels of circulating miR-21-5p before (p = 0.0091) and after (p = 0.037) NAC were associated with a statistically significantly worse overall survival (OS) . In a similar cohort of HER2-positive BC patients treated with NAC combined with trastuzumab, Liu et al. evaluated the association of circulating miR-21 levels with survival. The authors analyzed blood and serum samples from 83 HER2-positive BC patients during different phases of NAC (at baseline, after two cycles, and at the end of treatment). They demonstrated that changes in serum miR-21-5p levels were significantly associated with survival outcomes. In particular, patients in whom circulating miR-21-5p levels decreased from baseline to the end of the second cycle and to the end of NAC showed better OS and disease-free survival (DFS) than patients with increased levels of this miRNA . Similarly, an earlier study on HER2-negative BC confirmed that among the miRNAs investigated, a decrease in serum miR-21-5p and miR-125b-5p levels during NAC were associated with better DFS . MiR-21-5p has also been proven to be associated with survival outcomes in two other studies conducted on BC patients (any subtype) . In a study by Wang et al., conducted on more than 300 patients, high serum miR-21-5p levels were found to be an independent poor prognostic factor for both recurrence (HR 2.9; 95% CI 1.420-8.325; p = 0.008) and DFS (HR 2.7; CI 1.038-7.273; p = 0.003). In addition, patients with high miRNA levels had shorter recurrence-free survival (RFS) and disease relapse-free survival (DRFS) than patients with lower levels . Accordingly, in another study, elevated miR-21-5p levels in blood samples collected before and after NAC from 75 BC patients was found to be significantly associated with poor survival (p = 0.002) . It has been shown that circulating miR-34a-5p levels were associated with better survival outcomes in two studies conducted in HER2-negative BC. Liu et al. analyzed the serum miRNA levels of 86 patients during different phases of NAC and showed that changes in miR-34a-5p expression during treatment were significantly associated with treatment response and DFS. Furthermore, decreased miR-34a-5p levels between the end of the second cycle and the end of NAC compared to baseline levels were associated with improved DFS (p < 0.001) . In a more recent study, blood samples from 20 patients collected before and after the first cycle of NAC were evaluated to investigate whether circulating exosomal miRNAs could predict pCR. The authors showed that decreased levels of circulating exosomal miR-34a-5p were associated with better OS . Checkhun et al. analyzed the expression levels of circulating miRNAs in serum samples from 182 patients with luminal A and B BC undergoing NAC. The authors found that low serum miR-375-3p levels were associated with a lower rate of 3-year DRFS in luminal B patients. In contrast, higher levels of circulating miR-182-5p correlated with a lower 3-year DRFS rate in luminal A BC . Regarding the circulating miR-200 family in BC, a study evaluating serum miR-222-3p levels in a cohort of 65 HER2-positive patients receiving anti-HER2 NAC showed that low serum miRNA levels were associated with better DFS (p = 0.029) and OS (p = 0.0037). Moreover, the study aimed to assess the association between circulating miRNA levels and trastuzumab-related adverse events. For the first time, serum miR-222-3p levels were found to be an independent protective factor for cardiotoxicity (p < 0.05) and anemia (p = 0.013), although the mechanism of action remains to be elucidated . Finally, in a study conducted by Al-Khanbashi and colleagues, tissue and serum samples were collected from 27 BC patients undergoing NAC at four different timepoints (baseline, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, after the fourth cycle of docetaxel treatment) to assess the correlation between miRNA expression and different endpoints, including survival outcomes. The authors demonstrated that patients with high serum miR-451-5p levels at diagnosis were associated with better DFS (p = 0.046) . 5. Methodological Issues in Circulating miRNA Research The presented results reflect the heterogeneity of available data on this subject. Indeed, these findings mainly come from single studies, involving different BC subtypes and/or patient characteristics (ethnicity, age, tumor stage, grade), different therapeutic regimens, and different definitions of responders and non-responders, thus limiting result comparison. In addition, accordingly to the literature, the majority of the discrepancies could be due to pre-analytical and analytical variables, as well as to patient-related factors that can generate artifacts, thus prejudicing the quantification of circulating miRNAs . Specifically, one of the major critical issues is represented by the sample itself, including the type (plasma, serum, whole blood), collection (heparin, citrate, ethylenediaminetetraacetic acid, Paxgene tubes, sample handling), storage, processing (miRNA extraction method, timing of extraction), and blood cell contamination in sample preparation. In fact, it has been previously demonstrated that miRNAs contained in blood cells may have an influence on circulating miRNA analysis ; thus, different biological fluids show different circulating miRNA levels and whole blood may be strongly contaminated by blood cell miRNAs. In particular, the effect of haemolysis and the consequent release in the circulation of red cell miRNAs in impairing circulating miRNA analysis have been deeply investigated and proven . In addition, blood cell miRNA contamination may also occur during sample collection, due to different centrifugation protocols used to separate plasma and serum from whole blood and processing. For example, the correct choice of the anticoagulant for blood collection may, at least in part, prevent the lysis of red blood cells (e.g., citrate may trigger haemolysis) . Another critical issue in circulating miRNA analysis that may, at least in part, explain the inconsistency among studies is the detection method used and the lack of a robust and standardized method for data normalization . Since miRNA discovery, different quantification methods have been developed for miRNA analysis (e.g., quantitative real-time polymerase chain reaction (qRT-PCR), next-generation sequence (NGS), miRNA microarrays). Nowadays, qRT-PCR is the "gold standard" method since it allows a medium/high throughput and sensitive quantification of miRNAs. However, it can detect only annotated miRNAs, and the amplification step may affect miRNA quantification. NGS is a high-throughput method allowing the identification of both known and novel miRNAs with high sensitivity. However, it needs a larger quantity of each sample to be processed, it is the most expensive method, and it requires deep bioinformatics analyses. MiRNA microarrays are able to conduct high-throughput analysis on thousands of known and annotated miRNAs, but need to be constantly updated, thus impairing the comparison of results obtained with different platform versions. In addition, compared to NGS and qRT-PCR, miRNA microarrays show lower dynamic range and specificity . Normalization strategy is a key issue for all platforms used for circulating miRNA quantification. Different endogenous miRNAs have been proposed as possible intrinsic controls for circulating miRNA analysis , and, among them, miR-16-5p is the most commonly used. However, it has to be considered that erythrocytes have high levels of miR-16-5p; thus, haemolysis may impair its use as an internal control . Other normalization methods have been proposed (e.g., spiked-in synthetic RNAs, global normalization, quantile normalization); however, to date, a validated standardized normalization strategy has not yet been globally adopted. In addition, we have to consider that the normalization method may depend on the detection method used, thus further reducing the ability to compare results from different studies. Finally, we have to highlight that in some of the analyzed studies it is not specified which strand of miRNA (-3p or -5p) is under investigation and, therefore, the authors refer to the miRBase alias used for the guide strand. However, considering that it has been demonstrated that both strands can be incorporated into the miRISC complex depending on tissue or cell type and act in gene regulatory networks , specific information about the strand is fundamental for adequate result comparison across different studies. On the other hand, considering patient-related factors, as stated above, we should note that many results derived from single studies or from clinical studies enrolling a low number of patients, with no well-defined inclusion criteria , and with heterogeneous treatments. Moreover, we have to consider that circulating miRNA levels could be affected by various physiological conditions and/or comorbidities, such as obesity and diabetes, and these have to be taken into account during analysis . In addition, different studies have shown that circulating miRNA levels may be affected by individual factors, such as age, race, drug assumption, smoking habits, diet, and physical activity . Finally, we have to point out that BC is a heterogeneous disease, which may, at least in part, further explain the inconsistency of the results . 6. Conclusions To date, besides few clinical genomic classifiers , there is no validated predictor associated with NAC benefit in terms of pCR and, ultimately, DRFS. Our review pointed out that circulating miR-21-5p and miR-34a-5p are the most promising non-invasive biomarkers for BC patients in the NAC setting and deserve further investigations. The collection of miRNAs from biological fluids at the beginning of NAC is simple and may aid in the identification of patients who will receive the greatest benefit. On the other hand, assessing miRNA levels during NAC is straightforward and faster than radiological assessment and may serve as a red warning in cases of poor response, particularly when it is clinically challenging to assess. However, due to the disagreement between studies, further clinical trials with more precise patient inclusion criteria and more standardized methodological approaches are definitely needed to better define the predictive/prognostic ability of these promising non-invasive biomarkers in anticipating the treatment response and outcome of BC patients undergoing NAC. Author Contributions Conceptualization, R.D.S. and P.T.; methodology, R.D.S. and P.T.; investigation, P.T., C.B., F.J., M.G. and G.S.; writing--original draft preparation, C.B., F.J., M.G., G.S. and P.T.; writing--review and editing, P.T., S.P. and R.D.S.; supervision, R.D.S., A.Z. and A.S. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest The authors have no known competing financial interest or personal relationships that could have appeared to influence the work reported in the manuscript. Figure 1 Circulating miRNAs significantly associated with BC clinical-pathological features. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000234 | Rapidly changing environmental conditions (bioclimatic, anthropogenic, topographic, and vegetation-related variables) are likely to alter the spatial distribution of flora and fauna. To understand the influence of environmental variables on the Blue bull's distribution and to identify potential conflict zones, the habitat suitability analysis of the Blue bull was performed using ensemble modeling. We modelled the distribution of the Blue bull using an extensive database on the current distribution of the Blue bull and selected 15 ecologically significant environmental variables. We used ten species distribution modeling algorithms available in the BIOMOD2 R package. Among the ten algorithms, the Random Forest, Maxent, and Generalized linear model had the highest mean true skill statistics scores, ensuring better model performance, and were considered for further analysis. We found that 22,462.57 km2 (15.26%) of Nepal is suitable for the Blue bull. Slope, precipitation seasonality, and distance to the road are the environmental variables contributing the most to the distribution of Blue bull. Of the total predicted suitable habitats, 86% lies outside protected areas and 55% overlaps with agricultural land. Thus, we recommend that the future conservation initiatives including appropriate conflict mitigation measures should be prioritized equally in both protected areas and outside protected areas to ensure the species' survival in the region. ensemble modelling human-Blue bull conflict species distribution modelling environmental changes crop raiding retaliatory killing This research received no external funding. pmc1. Introduction The Blue bull (Boselaphus tragocamelus), commonly known as 'Nilgai', is Asia's largest antelope, a member of the Bovidae family listed as least concern globally . However, in Nepal, it is categorized as a nationally vulnerable species due to its declining population from suspected poaching, retaliatory killing, and habitat loss . It is the only sexually dimorphic ungulate of huge stature and distinctive color in the genus Boselaphus . This species has a wide distribution in the lowlands of Nepal and India, extending into the borders of Pakistan, and is now extinct from Bangladesh . The species has already been introduced in Texas, Mexico, South Africa, and Italy . In Nepal, it is distributed in protected and non-protected areas of the southern plains called 'Terai' across habitat types like grassy steppe forests, scrub areas, flood plains, dry deciduous forests, riverine forests, and the agricultural regions . It appears to thrive in Koshi Tappu Wildlife Reserve in the east, Parsa National Park in the middle, and Shuklaphanta and Bardia National Parks in the west . It prefers various habitat types, including hillsides, arid areas, grassy steppe forests, scrub areas, flood plains, dry deciduous forests, riverine forests, and agricultural areas . Due to its preference and dependency on agricultural land, it causes substantial financial losses and is now considered a pest in India and Nepal . As a result, retaliatory killing is prevalent, causing a drastic decline in the species' population in Nepal . In addition, its habitat is being fragmented and degraded due to increased human settlement, infrastructure development, overgrazing, and agricultural expansion, further threatening the country's population . Mapping and predicting potentially suitable habitats of threatened and conflict-creating taxa is critically essential from the monitoring and management perspective . The first step toward effective wildlife conservation is habitat assessment . It offers information on the quality and quantity of the habitat available for targeted species . Habitat modeling is primarily used in conservation planning to estimate the geographical distribution of appropriate habitats for species of interest in a landscape . Species distribution modeling (SDM), often referred to as ecological niche modeling, builds a species-environment relationship to explain and forecast the likely distribution of a species . SDM can be used as a conservation planning approach for threatened species by determining the species distribution range and ecological niche . Due to extensive data and multifaceted associations between species and ecological variables, the scope of machine learning methods such as SDM has increased to solve the problem of ecologists and statisticians . Besides, SDM helps to envisage the effects of climate change on species, which is essential to achieve the conservation goals of awareness of the species distribution . Several modeling techniques are assembled through the ensemble method in SDM to improve the projecting performance . However, a science-based conservation plan in Nepal needs to be improved to address these issues. Identifying suitable habitats across the region and mapping potential conflict zones help guide the conservation action for the long-term survival of this species. This study tried to explore the current suitable habitat and conflict zones across Nepal by applying the ensemble model. In this study, (a) we modeled the distribution of the Blue bull in Nepal based on bio-climatic, bio-physical, anthropogenic, and topographic variables using an ensemble modeling approach; (b) identified key factors affecting the Blue bull distribution; and (c) identified the potential conflict zones by combining the habitat suitability map with the land use and land cover map. We believe this study will be instrumental in prioritizing conflict zones and formulating proper conflict mitigation strategies to ensure the species' long-term conservation. 2. Materials and Methods 2.1. Study Area Nepal is a mountainous nation in South Asia. It covers an area of 147,516 km2 and is located between the latitudes of 26deg22'-30deg27' N and the longitudes of 80deg04'-88deg12' E. It is endowed with extensive biodiversity due to its variable climate and topography along a steep altitudinal gradient from 60 to 8848 m a.s.l. . Nepal can be divided into three main physiographic zones: the lowland (Terai and Siwalik), the mid-hills, and the high mountains . The climate is usually mild, with dry winters and rainy summers . Its mean annual precipitation is 1768 mm and the mean annual temperature is 18 degC . The Blue bull in Nepal is restricted to alluvial flood plains in the southern lowlands . The southern lowlands of Nepal are home to seven protected areas, including Shuklaphanta National Park (SNP), Bardia National Park (BNP), Banke National Park (BaNP), Krishnasar Conservation Area (KCA), Chitwan National Park (CNP), Parsa National Park (PNP), and Koshi Tappu Wildlife Reserve (KTWR) . 2.2. Data Collection 2.2.1. Blue Bull Presence Data The occurrence points of the Blue bull were obtained primarily from field-based surveys conducted between 2018 and 2021. The periodic data from the Department of National Park and Wildlife Conservation (DNPWC) and the Division Forest Offices (DFOs) obtained through personal communications were used as supplementary data. Direct observation, pellet droppings, and hoofmarks were used to confirm the Blue bull's presence in an area. In total, 179 occurrence points of the species were collected from the distribution range. The occurrence data were cleaned by removing duplicates and locations that tend to fall beyond the species' reported distribution area. We chose only one presence point if multiple presence points are available within a grid of 1 x 1 km using a SpThin package in R , given that environmental factors with a spatial resolution of 1 x 1 km were used to predict species habitat refugia. 2.2.2. Environmental Variables We used a combination of bioclimatic, anthropogenic, topographic, and vegetation-related variables for the habitat suitability model. We tried to include all the significant predictor variables because variable selection is an essential step in species distribution modeling (SDM) . We compiled 33 variables (Table 1) crucial for the Blue bull's habitat suitability modeling . Due to their ecological significance and ability to define annual patterns, seasonality, and extremes of temperature and precipitation, bioclimatic variables are widely employed in spatial modelling . To retrieve 19 bioclimatic variables, WorldClim-Global Climate Data ) was used . These data were obtained in a grid format with a spatial resolution of 1 x 1 km. The anthropogenic variables used in our model include distance to a human path, distance to roads, distance to settlements, human population density, livestock density, and land use land cover data. The data on the paths, roads, and buildings were extracted from Geofabrik's website . Data on settlements were assessed from the Nepalese Department of Survey, and a distance raster file was created using ArcGIS10.8.1 . The data on land use and land cover change was accessed from the ICIMOD . Similarly, human population density and livestock density data were accessed through the Humanitarian Data Exchange Dataset and Open Data Nepal . Topographic variables were included as predictor variables in our model. Using ArcMap 10.8.1 , elevation, aspect, and slope data were extracted from a Digital Elevation Model (DEM) with a 1 km spatial resolution that was downloaded from the US Geological Survey database . Water source shapefiles were collected from the Geobabrik website and transformed using ArcMap 10.8.1 into a distance raster file. The following four vegetation-related variables were collected for this study: forest cover, minimum Enhanced Vegetation Index (EVI), mean EVI, and maximum EVI. Forest cover was extracted from Earth engine partner Appspot . Moderate Resolution Imaging Spectroradiometer (MODIS) was used to download EVI time-series data. The Savitzky-Golay filter was used to smooth the data in the TIMESAT algorithm . This technique helped to reduce cloud cover in the surroundings and facilitated image visualization. Later, the average values of overall indices were calculated to obtain the final index of EVI. Next, the multi-collinearity test was performed among 33 environmental variables, and variables with correlation coefficients > 0.7 and variance inflation factor > 5 were removed to avoid multi-collinearity . After the multi-collinearity test, 15 predictor variables were left and used for habitat suitability modeling for the Blue bull in Nepal (Table 1). 2.3. Data Analysis 2.3.1. Blue Bull Habitat Suitability Modeling We used the overview, data, model, assessment, and prediction method described by Zurell et al. (2020) to develop habitat suitability models for the Blue bull in Nepal. Given its improved predictive accuracy , recent SDM exercises praise combining multiple models created using various modeling techniques into an ensemble map . Therefore, we also developed habitat suitability models for the Blue bull using an ensemble modeling approach. In order to generate ensemble models in R, the BIOMOD2 package was used (R Development Core Team 2020). Ten algorithms, including the artificial neural network (ANN), the classification tree analysis (CTA), the flexible discriminant analysis (FDA), the generalized additive model (GAM), the generalized boosting model (GBM), the generalized linear model (GLM), the multiple adaptive regression splines (MARS), the maximum entropy (MAXENT), the random forest (RF), and the surface range envelope (SRE) were used to create the ensemble models. We created 10,000 random pseudo-absence points, as postulated by Barbet-Massin et al. (2012) , by assigning equal weight to the presence and pseudo-absence datasets and repeating the pseudo-absence generation three times to minimize random bias. The Blue bull's presence and pseudo-absence data were split into training (70%) and testing (30%) data sets. Our modeling approach included ten algorithms, three pseudo-absence selection runs, and three evaluation runs. This yielded a total of 90 model runs. The receiver operating characteristics (ROC) curve, referred to as area under the curve (AUC) , and true skill statistics (TSS) are two independent techniques that are frequently used to evaluate the accuracy of predictive distribution models . Despite its widespread use as a model evaluation metric, AUC has been rebuked for its limitations . Therefore, the TSS evaluation criterion (-1 to +1) was used to assess our model's predictive performance. If the TSS value is +1, the model is considered perfect, whereas a TSS value between 0.7 and 0.9 indicates a good model . We used the weighted mean approach to build an ensemble model from all models with a TSS value greater than 0.6 . Three models (GMB, MaxEnt, and RF) have TSS value greater than 0.6 and hence were used to develop the weighted mean ensemble approach. 2.3.2. Potential Conflict Zones Mapping To map potential human-Blue bull conflict zones, we overlaid the suitable habitats over the cropland extracted from the LULC map downloaded from the ICIMOD website . The overlapped area was then extracted. 3. Results 3.1. Predicted Suitable Habitats for the Blue Bull The habitat suitability map generated using an ensemble modeling approach showed that 22,462.57 km2 (15.26%) of Nepal is suitable for the Blue bull . Of the total suitable habitat (22,462.57 km2), only 14.27% (3204.35 km2) falls inside the protected area management system, while 85.73% (19,257.16 km2) is located outside the protected area system. The buffer zone of Koshi Tappu Wildlife Reserve has the highest proportion of suitable area (100%), followed by Shukhlaphanta Buffer Zone (94%), Chitwan National Park (91%), and Shuklaphanta National Park (89%), out of all management systems. Protected areas, mainly covering the mid-hill area, had the lowest proportion of suitable habitat. Out of the total suitable habitat area included inside the protected areas, Chitwan National Park contained the highest proportion of suitable habitats (27%), followed by its buffer zone (16%, see Table 2 for more details). We also found that most of the predicted suitable habitat occurs in the Terai and the Siwalik regions of Eastern and Central Nepal . 3.2. Factors Affecting the Blue Bull's Distribution in Nepal Of the 15 predictor variables used to model the suitable habitats for the Blue bull, slope contributed the most to the model, followed by precipitation seasonality (see Table 3 for detail). The response curves of GLM, MaxEnt, and RF indicate that the probability of occurrence of the Blue bull decreases with an increase in slope; more specifically, areas with slope > 10 degrees are unsuitable for the Blue bull, whereas it peaks in areas with precipitation seasonality between 95 and 130 . Furthermore, the suitability decreases with an increase in distance to road . 3.3. Models Accuracy in Predicting the Current Suitable Habitat of the Blue Bull Among the ten algorithms, RF, Maxent, and GBM had the highest mean TSS scores, ensuring better model performance. Regarding predictive performance, the ensemble model surpassed (0.89) single algorithm models based on TSS . 3.4. Potential Human-Blue Bull Conflict Zones Upon layering the suitable habitat of the Blue bull over the LULC layer, we found that agricultural land overlaps with 54.8% of the total suitable area of the Blue bull and with 45.2% by other land use categories (forest 34%, shrubland 1%, grassland 2%, barren land 5%, water body 2%, and built-up areas 1%) . 4. Discussion In this study, we modeled the potential distribution and mapped the potential conflict zones of the Blue bull in Nepal. We found that 22,462.57 km2 (15.26%) of Nepal is suitable for the Blue bull . Slope, precipitation seasonality, and distance to the road are the environmental variables contributing the most to the Blue bull habitat suitability models. Almost 55% of the predicted suitable habitats fall under agriculture land use, suggesting that these areas could be potential human-Blue bull conflict zones . Below we discuss the mechanisms likely to underlie the aforementioned findings. 4.1. Predicted Suitable Habitats for the Blue Bull This study predicted that 22,462.57 km2 of Nepal is suitable for the Blue bull , which is 4200 km2 more than the area (18,213 km2) estimated by Jnawali et al. (2011) . In the last decade, Nepal's forest coverage, particularly outside the protected areas, increased from 37% to 44.74% , which might have contributed to this increase in the predicted suitable habitat for the Blue bull in Nepal. Besides, the predicted wider distribution of the Blue bull can be explained by its generalist nature. The Blue bull can survive in various habitats like arid areas, scrub, grassy plains, dry deciduous open forests, and agricultural areas . Ref. reported that the Blue bull is found in the protected areas (Chitwan National Park, Bardia National Park, Koshi Tappu Wildlife Reserve, Parsa National Park, and Shuklapanta National Park) as well as outside of them in Parsa, Rupandehi, Nawalparasi, Kailali, Kanchanpur, and Bardia districts. The presence of the Blue bull outside protected areas in Nepal was also documented by Ref. , who recorded 40 Blue bulls from grasslands and open forests of the Tinahu river of Rupandehi district; Ref. reported 303 Blue bulls from Rupandehi; Ref. reported 15 Blue bulls from Laljhadi Mohana Biological Corridor; Ref. documented Blue bulls from the fragmented habitats of the Sarlahi, Rautahat, and Kamala River of Central Nepal; and Ref. recently reported a Blue bull from the Jalthal forest of Jhapa in Eastern Nepal. In line with the findings of these studies, we also found that more than 85% of the predicted suitable habitats lie outside the protected areas. This suggests that the future conservation initiatives should not only prioritize protected areas (as most of the conservation initiatives in Nepal are) but also consider species conservation outside protected areas and establish corridors and connectivity among the forest patches outside of protected areas to ensure the species' survival in the region. 4.2. Factors Affecting the Blue Bull's Distribution in Nepal We found that slope, precipitation seasonality, and distance to the road are the environmental variables contributing the most to the Blue bull habitat suitability models . More specifically, we found that areas with slope < 10 degrees are suitable for the Blue bull. This is in line with , which suggest that flat areas and the marginal slopes are preferred by the Blue bull. About precipitation seasonality, the probability of occurrence of the Blue bull was found to be maximum in the areas with precipitation seasonality ranging between 95 and 130, suggesting that eastern and central lowlands of Nepal that receive heavy rainfall during monsoon and little or no rain during other seasons are more suitable for the Blue bull . This might have to do with the mixed feeding nature of the Blue bull, since it prefers to feed from various grass species , and precipitation seasonality favors the growth of mixed plant species and maintains seasonal grassland dynamics . With the increased rainfall, the forest becomes dense, with little grassland area to support the low-density terrestrial herbivores . Ref. reported that open habitats are preferred by the Blue bull, which coincides with our findings that suggest that areas closer to the roads are more suitable for the Blue bull. Ref. reported that despite having higher human disturbance near roads or human settlements, the Blue bull prefers to remain on the edge of the forests and agricultural land due to a higher species diversity in these regions. The Blue bull indeed has been reported to be more tolerant to human disturbances than other ungulates such as the Sambar and Chittal . Moreover, research has revealed that the Blue bull tends to avoid dense forests and to inhabit open grasslands, margins, and buffer zones with low-density forests to reduce the risk of predation, since it can have better visibility of tigers in open and low-density habitats . Such phenomena of avoiding dense forests could make them more likely to reside in the buffer zones and outside the protected areas, increasing the conflict with humans. Concerning precipitation seasonality, the probability of occurrence of the Blue bull was found to be maximum in areas with precipitation seasonality ranging between 95 and 130. The lowlands in Central and Eastern Nepal that receive heavy rainfall during monsoon and little or no rain during other seasons hold higher suitability. Additionally, precipitation influences the growth of plant species and grassland dynamics . The Blue bull is a mixed feeder that prefers to feed from various grass species . As precipitation rates increase, the forest ecosystem experiences an increase in vegetative density, resulting in a reduction of grassland habitats. This restricted availability of grassland resources may limit the carrying capacity of low-density terrestrial herbivores within the ecosystem . 4.3. Potential Human-Blue Bull Conflict Zones We found that almost 55% of the predicted suitable habitats overlap with agriculture land, suggesting that these areas could be potential human-Blue bull conflict zones . Such considerable overlap could be an indication of the phenomenon that the Blue bull tends to avoid dense forests and to occupy open grasslands, edges, and buffer zones with low-density forests to avoid predation risk. However, this might subsequently lead to increased human-Blue bull conflict. Indeed, human-Blue bull conflict, particularly crop damage, has been reported to cause substantial financial losses in India and Nepal. In response to such conflict, retaliatory killing is prevalent in India and Nepal . Importantly, illegal hunting, electric fencing, poisoning, and habitat deterioration have become significant threats to the Blue bull in a human-dominated landscape . Thus, proper conflict mitigation strategies should be adopted. In response to the ongoing human-Blue bull conflict, several mitigation measures have been employed by farmers. Fences, crop guards, night lights, drum beating, and dogs in the buffer zone of Bardia National Park , as well as firecrackers, trenches, electric fences, and scarecrows in Rupandehi have been used frequently. Similarly, Refs. have suggested that the cooperative guarding of crops during the harvesting season, changing cropping patterns, using (olfactory, acoustic, and visual) repellents, fencing, translocation, physical barriers, and sterilization could be beneficial to mitigate crop loss from the Blue bull and reduce the retaliatory killing. 5. Conclusions This study is the first of its kind to model the potential distribution and mapped the potential conflict zones of the Blue bull across Nepal. In this sense, it has established a baseline about the suitable habitats for the Blue bull and the potential human-Blue bull conflict zones in Nepal. We found that over 15% of the country's land is suitable for the Blue bull, which is much higher than earlier estimates. We also found that the majority of the predicted suitable areas lies outside of the protected areas, which in turn suggests that the future conservation initiatives should not only prioritize protected areas but also consider species conservation outside of them. Similarly, establishing corridors and connectivity among the forest patches outside of protected areas could ensure the species' survival in the region. We also found that the Blue bull prefers the flat lowlands of Eastern and Central Nepal with clear monsoon and dry season, and we confirm that it tends to avoid dense forests and to occupy edges and agricultural land around the forests. This in turn is likely to aggravate human-Blue bull conflict in future. Thus, proper conflict mitigation strategies should be adopted, and earlier studies have suggested that the cooperative guarding of crops during the harvesting season, changing cropping patterns, using (olfactory, acoustic, and visual) repellents, fencing, translocation, physical barriers, and sterilization could be beneficial to mitigate crop loss from the Blue bull and reduce retaliatory killing. Acknowledgments We thank Rabin KC of the National Trust for Nature Conservation, Bardia, Kamal Kafle and Suman Bhandari of Chitwan National Park, Navaneet Misthra of DFO Rautahat, Aavas Pradhan (Snake Conservation Society Nepal), and Prashant Rokka (Sarlahi) for their assistance in data collection, and the Tribhuvan University, Institute of Forestry, Pokhara Campus, for providing research facilities. Open access was funded by Helsinki University Library. Author Contributions Conceptualization, B.D., A.B. and H.A.; field data collection, B.D. and A.B.; methodology, B.D., A.B., B.A. and H.A.; laboratory work, B.A., B.D. and A.B.; software, B.A.; validation, B.D., H.A., S.K.M., A.B., B.A. and M.S.M.; formal analysis, B.A., H.A. and S.K.M.; investigation, A.B. and B.D.; resources, A.B. and B.D.; data curation, B.D. and A.B.; writing--original draft preparation, A.B., B.D., D.N., H.A. and S.M; writing--review and editing, B.D., H.A., D.N., S.K.M., A.B., B.A. and M.S.M. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data that support the findings of this study are available from the first author, [B.D.], and second author, [A.B.], upon reasonable request. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Map of Nepal showing the location of the protected areas of different categories. The blue dots show the current distribution locations of the Blue bull across Nepal. Figure 2 Predicted suitable habitats (orange color) for the Blue bull in Nepal. The protected areas of different categories across Nepal are also shown. Figure 3 Response curves indicating the effects of different environmental variables on the habitat suitability of the Blue bull in Nepal. Figure 4 Performance predictions of various modeling approaches used to develop a current suitable habitat model based on true skill statistics. Figure 5 Map showing the overlap between suitable habitats of the Blue bull and different land use categories. animals-13-00937-t001_Table 1 Table 1 A complete list of environmental variables compiled for this study. Environmental variables used for habitat suitability modeling for the Blue bull in Nepal are indicated by bold letters. Source Category Variable Unit WorldClim Bioclimatic BIO1 = Annual Mean Temperature degC BIO2 = Mean Diurnal Range (Mean of monthly (max temp-min temp)) degC BIO3 = Isothermality (BIO2/BIO7) (x100) % BIO4 = Temperature Seasonality (standard deviation x 100) degC BIO5 = Max Temperature of Warmest Month degC BIO6 = Min Temperature of Coldest Month degC BIO7 = Temperature Annual Range (BIO5-BIO6) degC BIO8 = Mean Temperature of Wettest Quarter degC BIO9 = Mean Temperature of Driest Quarter degC BIO10 = Mean Temperature of Warmest Quarter degC BIO11 = Mean Temperature of Coldest Quarter degC BIO12 = Annual Precipitation mm BIO13 = Precipitation of Wettest Month mm BIO14 = Precipitation of Driest Month mm BIO15 = Precipitation Seasonality (Coefficient of Variation) % BIO16 = Precipitation of Wettest Quarter mm BIO17 = Precipitation of Driest Quarter mm BIO18 = Precipitation of Warmest Quarter mm BIO19 = Precipitation of Coldest Quarter mm USGS Topographic Elevation km Aspect Degree Slope Degree GEOFABRIK Distance to water km Landsat Vegetation-related Mean EVI, Minimum EVI, Maximum EVI (Enhanced Vegetation Index) Dimensionless GFC Forest Dimensionless Department of Survey, Nepal Anthropogenic Distance to settlement km GEOFABRIK Distance to the motor road km Distance to path km HUMDATA Population density Dimensionless Livestock density Dimensionless ICIMOD LULC km animals-13-00937-t002_Table 2 Table 2 The significant protected areas and areas of predicted suitable habitats for the Blue bull in Nepal. Protected Areas (PAs) Total Area (Km2) Total Suitable Area (Km2) Area (%) of Suitable Habitat Out of the Total Area of Specific PA Area Covered within Specific PA Out of the Total Suitable Area within PA Shuklaphanta National Park 305 270.64 89% 8% Buffer Zone 243 228.78 94% 7% Bardia National Park 968 152.84 16% 5% Buffer Zone 327 162.67 50% 5% Banke National Park 550 111.29 20% 3% Buffer Zone 344 149.59 43% 5% Chitwan National Park 952 873.75 91% 27% Buffer Zone 750 518.83 69% 16% Parsa National Park 499 264.26 53% 8% Buffer Zone 298 51.14 17% 2% Koshi Tappu Wildlife Reserve 175 150.12 86% 5% Buffer Zone 173 173 100% 5% Annapurna Conservation Area 7629 34.63 0% Less than 1 Shivapuri National Park 159 26.23 16% Less than 1 Black buck Conservation Area 16 12.68 79% Less than 1 animals-13-00937-t003_Table 3 Table 3 Percentage contributions of environmental variables to the model. Environmental Variables Generalized Linear Model MAXENT.Phillips.2 Random Forest Ensemble Percentage Contribution Slope 0.598 0.71 0.142 0.483 31% Aspect 0.075 0.019 0.005 0.033 2% Mean diurnal range 0 0 0.023 0.008 0% Isothermality 0.212 0.043 0.005 0.087 6% Precipitation of driest month 0.209 0.102 0.021 0.111 7% Precipitation seasonality 0.492 0.027 0.03 0.183 12% Precipitation of warmest quarter 0.202 0.042 0.015 0.086 6% Precipitation of coldest quarter 0.095 0.049 0.045 0.063 4% Distance to path 0.252 0.122 0.002 0.125 8% Distance to the motor road 0.065 0 0.003 0.023 1% Distance to settlement 0.14 0.072 0.014 0.075 5% Distance to water 0.086 0.004 0.006 0.032 2% Forest 0.128 0.159 0.04 0.109 7% Population density 0.048 0.162 0.052 0.087 6% Livestock density 0.086 0.007 0.019 0.037 2% Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000235 | There is growing evidence for trained assistance dogs promoting the health, wellbeing, and quality of life of people in a variety of circumstances, including for those with dementia. Little is known about people with younger (early)-onset dementia (YOD) and family carers. As part of a larger study involving 14 people with YOD matched with trained assistance dogs over a two-year period, we report analyses of interviews with 10 family carers conducted on multiple occasions investigating their experience with an assistance dog. Interviews were recorded, transcribed and subjected to inductive thematic analysis. They told a range of experiences; the good and the challenging. Findings fell into three areas: the human-animal bond; relationship dynamics; and responsibility for caring. Concerns were raised with respect to the resources required of carers together with the financial resources needed to support an assistance dog. The study concludes that trained assistance dogs can play an important role promoting the health and wellbeing of both people with YOD and of their family carers. However, support needs to be in place as the circumstances of the family member with YOD changes and the role of the assistance dog as part of the family also changes. Practical (financial) support of a scheme such as the Australian National Disability Insurance Scheme (NDIS) could be important to sustaining such support. Alzheimer's assistance dogs animal-assisted therapy human-animal bond younger onset dementia early onset dementia carers wellbeing State Trustees Australia (Victoria), Gandel Philanthropy, and Petbarn AustraliaSeeing-eye Dogs Australia and Dementia AustraliaThe project received funding from State Trustees Australia (Victoria), Gandel Philanthropy, and Petbarn Australia. The project also received considerable in-kind support from Seeing-eye Dogs Australia and Dementia Australia. pmc1. Introduction In Australia, there are an estimated 487,500 people living with dementia , which is the second leading cause of death in Australia . Notably, rates of dementia are on the rise in Australia, with an average of 250 being reported every day, and an expected 318 per day by 2025. Similarly, in Japan, USA and UK it is expected that 1 in 3 people will develop dementia in their lifetime with the most common being Alzheimer's . Furthermore, research commissioned by Dementia Australia estimate there to be about 1.6 million Australians involved in the care of someone living with dementia. In the USA, this figure is estimated to be over 11 million . While the vast majority of people with dementia are over 65 years old when diagnosed, 5% to 6% of people with dementia will have younger-onset dementia (YOD), also known as early-onset dementia (EOD) . YOD is used to describe any form of dementia diagnosed in people who are younger than 65 years old. It is far less common than dementia diagnosed when an individual is over 65 and has been diagnosed in people as young as in their 30s. When diagnosed, these individuals are typically living at home with a partner and often have parental responsibilities for their children or younger family. Busted, Nielsen, & Birkelund report that individuals with YOD experience a range of emotions such as fear of a loss of control over oneself, becoming a burden on their family, fear of a humiliating future, and a loss of their sense of self and who they are as a partner, parent and person. Bannon et al. report that those diagnosed with YOD and their family carers experience a range of stressors that impact their health and wellbeing. These include: difficulty understanding the diagnosis and/or disease trajectory; life being "turned upside down"; a sense of loss of anticipated future and "golden years" together; negative emotions such as anxiety, anger, grief, despair, and hopelessness; feeling overwhelmed with information as they connect with support services; and a lack of acceptance or denial of one partner interfering in a couple's ability to adjust together. These can be exacerbated as the person with YOD deteriorates cognitively and physically (including loss of the ability to speak, walk and loss of continence), and their behaviors become erratic and at times aggressive. As there is no known cure for dementia, the primary focus of intervention and support is to maintain the person's quality of life. This is achieved through a combination of activities designed to maximize their engagement with and independence in daily activities, sustain recognition of their immediate environment and significant others, promote social engagement, and stabilize mood and behavior. Importantly, intervention and support are also needed to foster a safe living environment. Johannessen, Helvik, Engedal, and Thorsen report that as part of a holistic intervention, it is also very important to address the psychological and practical needs of partners providing care through individualized interdisciplinary support throughout the progression of YOD. The need to focus on the support of partners providing care is further highlighted by Werner, Spiegelman and Turgeman who identify several types of stigma adversely impacting carers of those with YOD; including public stigma reflected in social distancing and discrimination by others in the community, courtesy stigma where relatives and friends distance themselves, structural stigma where professionals decline to provide services, and personal negative emotions where partners report feeling embarrassment and shame and as a consequence guilt. Trained assistance dogs might offer one means of effective non-pharmacological intervention for those living with dementia and potentially also for family members providing care . Notably, potential benefits have been observed for both the person with dementia and their family, particularly in relation to the human-animal bond (i.e., the positive roles that animals can play in the integrated health of individuals, families and communities), relationship dynamics and the responsibilities of caring . Such findings reflect research in the general population, where interactions and activities with dogs have been shown to both promote behaviors known to increase wellbeing (e.g., walking), and to more directly affect human wellbeing . In particular, tactile interactions and playing with a dog have been found to be beneficial for hedonic wellbeing (i.e., that which is achieved through pleasurable experiences), while participating in activities such as dog training and caring for a dog have been found to contribute to eudemonic wellbeing (i.e., that which is achieved through pursuing self-improvement and realizing ones' best self) . This study was informed by a systematic review of peer-reviewed literature . The review focused on the efficacy of trained assistance dogs as an intervention and support for people experiencing dementia. However, the review was unable to identify literature specifically addressing the health and wellbeing of those with YOD, nor was it able to identify literature documenting the experience of family carers supporting a person with YOD. Since the publication of Marks and McVilly , Santaniello et al. have conducted a 7-year retrospective analysis of 127 Alzheimer's patients and concluded that animal-assisted therapy involving dogs has promising potential in its efficacy in the treatment of cognitive deficits arising from Alzheimer's disease. Furthermore, Ritchie et al. have undertaken an initial investigation based on the reports of carers exploring the effectiveness of canine-assisted interventions for people with dementia in Scotland. However, there is still no evident literature focusing on the experience and effect of trained dementia assistance dogs specifically for people with YOD and their family carers. Consequently, the project of which this study forms a part was among the first properly constituted longitudinal research into the efficacy of assistance dogs for people with YOD. It provided a framework within which to develop training for assistance dogs for use with people with YOD, safely place the dogs and investigate their impact on the lives of both people with YOD and on their families. This study, the first from a larger project, reports on the experience and impact of trained assistance dogs on family members in the carer role for persons with YOD. 2. Methodology 2.1. The Context for the Study The larger project was designed to evaluate the effects of assistance dogs on the quality of life, health and wellbeing of people with YOD and family members providing support and care. The methodology was developed which documented the extent to which people with YOD, if provided with a trained dementia assistance dog, would be able to sustain their physical and emotional wellbeing, and self-manage the behavioral sequelae associated with dementia. Furthermore, the project monitored the engagement of participants with YOD in a range of practical everyday tasks that fostered physical health, together with their exercise of choice and self-determination. Finally, the project examined the impact of the assistance dog program on the homeostatic wellbeing of a family member, identified as the 'primary carer' for the person with YOD. The term homeostatic wellbeing is derived from an analogy between the physiological management of, for example, body temperature by the autonomic nervous system and the maintenance of subjective wellbeing theorized to be managed as an interplay of neurological systems the result of which is experienced in mood states such as happiness and sadness . Both quantitative and qualitative data were gathered, though in this paper we focus on the qualitative analysis of the family members' narratives collected by means of individual semi-structured interview on multiple occasions. Data collection took place over a period of up to two years, depending upon the progression of the disease for individual participants and their family circumstances. As the YOD progressed, some participants declined in their ability to contribute to the interview process. 2.2. Ethics The protocol for this research was reviewed and approved by the supervising institution's Human Research Ethics Committee (HREC); approval number 1647054. An application was also made to the host institution's Animal Research Ethics Committee but was subsequently exempted from the need for formal approval with the Animal Ethics Committee satisfied that the wellbeing of the dogs was sufficiently addressed in the human research ethics protocol; including pre-checks on the prospective families with which the dogs were to be placed and the physical environment of the house and garden, follow up wellbeing checks were arranged for post placement, and a protocol for withdrawal of the dogs agreed to with families prior to placement. All data reported in the final analysis, such as descriptions and interpretations of induced themes, have been anonymized to protect the privacy of participants and carers. However, it is acknowledged that since several the participants have chosen to participate in documentaries, television broadcasts, newspaper reports, and present at conferences, as well as five families living in regional or rural communities, it may be possible for some participants to be identified. These participants and their cares were aware of this risk at the time data were collected and gave consent accordingly. 2.3. Participants The carers who are the primary focus of the current study were the partners and adult children of participants with YOD. Participants with YOD and their carer/partners were recruited into the program and matched with assistance dogs with the support of a national dementia advocacy organization. The protocol for this recruitment and matching process was developed by the assistance dogs training organization, with reference to the protocols used to match persons who are blind or with low vision to Seeing-eye (Guide) dogs. Importantly, this protocol also took into account the safety and wellbeing of the dog. Participants with dementia were medically diagnosed with YOD, occurring prior to 65 years of age, and of the Alzheimer's type. There were five women and five men. The mean age of participants with dementia was 61 years 1 month (ranging from 53 years to 65 years of age), and seven of the participants were urban residents, and the remainder lived in a regional or rural area. Their carers were predominantly life partners (n = 12), with the occasional adult offspring also providing primary carer support (n = 2). Three of these triads (i.e., the person with YOD, the carer and the assistance dog) subsequently left the program: one to travel overseas for a year, one because of later discovering dog hair allergies, and a third prior to the allocation of their dog. A fourth triad left the program when the dog needed to be repatriated due to ill health. Of the 10 remaining triads, whose data form the basis of the current analyses, three had a partner with dementia who went into care during the period of the research, and the final seven remained at home for the full two-year duration of the project. While the primary focus of the current study is on the carers, the experiences and consequently the stories of the carers, their partners with dementia, and the dogs were intertwined. The experience of the participants with dementia often gave important context to that of the carers' reported experiences. This intertwining of experience is consequently reflected in the data and subsequent analysis. As noted earlier, pseudonyms have been used to maintain participant anonymity. In the brief descriptions that follow, the pseudonym of the person with YOD comes first, followed by that of the family carer and then the assistance dog. 2.3.1. Participants who Went into Care during the Program Case study #1--Sandra, Peter and their dog Aspen. Sandra and her partner and carer Peter lived in the outer suburbs of a large city and withdrew from the program between the second and third interview because Sandra went into care and could not take the dog. The family spent considerable time equivocating about this, but Peter needed to seek full-time employment, and did not feel he could commit to providing support for the dog, consequently Aspen was returned to the program. Case study #2--Cathy, Michael and their dog Beth. The domestic situation for this couple was very different to that of other participants. The family lived in an apartment that required access by a keyed password to the building, and then to the lift. This made it impossible for Cathy to take the dog out by herself, although whether or not she would have been able to do so in different living circumstances was unclear. Cathy went into care, but the family kept Beth and Michael took Beth to see Cathy at the nursing home regularly. Case study #3--Stephen, Michelle and their dog Andrew. Stephen and Michelle lived in an inner suburb of a large city. At the time of the first interview, Stephen's dementia was already quite advanced, and Michelle was struggling to provide the necessary care. It was causing her a great deal of anxiety. It was reported that Andrew was too much stress and worry for Michelle to handle as Stephen's support needs increased and consequently Andrew was returned to the program. 2.3.2. Participants who Were in the Program for the Duration of the Interview Period (Two Years) Case study #4--Jason, Annabelle and their dog Maxwell. Jason and his partner Annabelle, were both in their 60s and had been together for over 30 years, were both tertiary educated, and had both worked in professional roles. They lived in a regional center and were very active socially and politically. They had additional paid care-workers to help meet Jason's relatively high support needs, and they made regular use of respite care for several weeks at a time. Case study #5--James, Sue and their dog George. James and his partner Sue had been married for forty years. James completed form 3 at high school and worked in retail until being diagnosed with YOD. This couple lived in a regional center, and had adult children and grandchildren, living both locally and in other states. Sue still worked almost full-time, and James was home alone most of the day. They also minded grandchildren on a regular basis, but not when James was home alone. Case study #6--Linda, Jeff and their dog Ellie. Jeff and Linda lived in a large regional city. They had three adult daughters who did not live at home. Both were very physically active. The couple had lived and worked overseas, and Jeff was of a European migrant family. This couple had always had dogs in their households. Case study #7--Marcus, Lynette and their dog Jasper. Marcus and his partner Lynette lived on the outskirts of a small rural town located on an island, where they had moved recently following Marcus' diagnosis. They both had teaching backgrounds in different disciplines, and had adult sons, and several grandchildren. They were both in their late 50s at the time of the first interview and had been married for nearly 40 years. Marcus came from a family that had never had dogs, so having a dog of his own was a new experience for him. Case study #8--Cassie, Chris and their dog Raymond. Cassie and Chris lived in a rural town, where they had lived for many years. Chris had been in a leadership role in a large regional school, was a highly qualified teacher with several master's level qualifications, and at the time of the first two interviews, was still working part-time within the school, despite his memory loss, and was still driving a car. Cassie worked in a government department at a senior level, but by the third interview had taken some extended leave. Close family ties existed, with Chris living in a nearby regional town, with one adult son living locally and working nearby. Case study #9--Hugh, Marlene and their dog Jones. Hugh and his wife Marlene emigrated to Australia some decades earlier. They lived in a unit on the outskirts of Melbourne, and their adult son lived nearby. Hugh had been a tradesman and an athlete when he was younger. Hugh's dementia was very advanced before the dog was allocated. At the start of their involvement in the research, Hugh's speech was very difficult to understand. He had trouble moving around the room and maintaining balance, and his sight was bad. Case study #10--Sandy, Damian and their dog Jessie. Sandy was in her 60s, and Damian in his early 70s. They had two adult children and had been married for over 40 years. At the time of the first interview, they were living in their long-standing family home in the outer suburbs of a large city but were in the process of transitioning to a property on the outskirts of a small rural town. Sandy was already spending several days a week at the property, while Damian was attending to business in the city. By the time of the third interview, they were both permanently living at the rural property. 2.3.3. The Assistance Dogs Assistance dogs have been defined in various jurisdictions across Europe, the USA and Australia . In the USA, they are referred to as 'service animals' in the Americans with Disability Act . They are distinguished from 'therapy dogs' in that assistance dogs are matched and placed with specific people for prolonged periods to help with identified needs. This is in contrast to therapy dogs that augment the work of practitioners across multiple clients for shorter-term interventions. They are also to be distinguished from 'companion dogs'. In Australia, assistance animals, including dogs, are defined in the Commonwealth Disability Discrimination Act , and there are state-based registration schemes. Similarly, in New Zealand, discrimination against persons relying on or training an Assistance Dog may be considered a breach of the Human Rights Act 1993 (S21) and/or the Dog Control Act 1996 . Generally, before being registered, an assistance dog must first pass a 'public access test' (i.e., the minimum standard an assistance animal must meet to be considered safe and effective in accessing public places and public passenger vehicles). Notably, as trained and registered assistance dogs, the dogs in the current project were able to accompany their owners on public transport and into cafes, restaurants, cinemas, and other public places where other dogs (pets) would not ordinarily be allowed. The dogs were sourced as puppies from breeding stock originally intended to be trained as Seeing-eye (guide) dogs for the blind and people of low vision. They were then trained by an organization experienced in the training of Seeing-eye (guide) dogs for people who are blind or of low vision. The training process took place when the dogs were around 12-14 months old. At that stage all of the dogs had passed their first year of basic Seeing-eye (guide) dog training, obedience and general management. Both the training and the placement protocols took into account what has subsequently been referred to by Salmon et al. as "the animal's right to flourish or to lead a life worth living where mutual benefit exists for both animal and human" (p. 3250). The protocol for training was developed in consultation with a national organization involved in the support of people with dementia, including those with YOD. Additionally, the dog trainers underwent dementia-specific training and consulted with a project reference group comprising people with YOD. Training tasks included: head on lap (on demand); fetch the carer; dog follows participant throughout the house unless commanded otherwise; find object (mobile telephone, glasses, etc.); stop at kerb; and tug and response games (i.e., where the dog waits for a command to take a toy and then waits for a commend to release the toy). All dogs were trained to walk in harness, and in the usual skills expected of Seeing-eye (guide) dogs for the blind. 2.4. Data Collection and Analysis This project utilized a multiple single case study approach. For the current study, all data were collected by semi-structured interviews conducted in the participants' homes. All interviews were conducted by the first author. While participants were typically interviewed in the presence of their family carer because of their communication support needs, family carers were usually interviewed separately. The current analyses focus on the qualitative data arising from the interviews with family carers. Interviews were conducted at three points: time 1 baseline assessment, which occurred about 6 weeks into the program once suitability had been ascertained and before participant-specific dog placement and training began (at between weeks 7 and 10); time 2 at about week 24, once dogs had been placed, participants trained, and participants, carers and dogs had been assessed as suitable and 'graduated'; and time 3, at least one year later, which in some cases took place at up to 18 months after the original placement. Interviews were audio recorded and transcribed for analysis. Interview transcripts were first analyzed using Inductive Thematic Analysis to pinpoint recurrent themes within and across the case studies. The coding of emergent themes within the thematic analysis enabled an understanding of their frequency and generated a complex picture of the value of dementia assistance dogs and associated challenges. The extent of these analyses took into account the relatively small sample size. However, because the data from the various case studies were gathered over a period of up to two years, it was possible to develop rich insight into the participants' circumstances. Data were initially analyzed by the first author and the formulation then reviewed by the second author. Any discrepancies were conciliated by means of discussion and the coding reviewed as required. The results were subsequently organized deductively, informed by the findings of Ritchie et al. , who observed that outcomes (for both participants and their carers) fell into three key areas: the human-animal bond; relationship dynamics; and responsibility for caring. We also found these categories emerged in our analysis. Additionally, we found evidence for the positive effects the assistance dogs had on carer wellbeing, which extended beyond the time when the person with dementia needed to move into out-of-home care. 3. Results and Discussion 3.1. Human-Animal Bond The bond between human and animal is regarded as both mutualistic and dynamic in that it influences the behavior and wellbeing of both the animal and the human. . Over history, the nature of this bond has evolved, especially in relation to the bond between the dog and humans. As Ritchie et al. discovered, we also found that each individual involved with the project, whether they are a partner/carer, family member, or people with dementia, developed their own, individually diverse relationship and bond with the assistance dog. These bonds were highly variable, not only between the carer/family members, and person with dementia, but also across the project within different families. An example of the way the human-animal bond worked was seen when Stephen (CS#3) went into full-time care, but his partner Michelle continued to bring Andrew (the assistance dog) to visit Stephen in the care facility. Stephen, it transpired, believed he was an employee of the care facility, and that he was earning money to support the dog and his family. Michelle reported "It makes him feel important!" This gave Stephen a renewed sense of purpose through his bond with the dog. Indeed, shortly before the time of the interview, Stephen had been having great difficulties with being in care, and according to his support worker, having the dog visit had been seen as one of the calming influences. As Michelle noted: "The bond between them. You can see it's great". The role of the dog in providing companionship, and the opportunity for tactile contact, were seen as highly significant in supporting Stephen. More pertinently, for this paper, seeing Stephen develop a human-animal bond with his assistance dog, and accordingly, a sense of purpose, gave his partner Michelle a greater bond with the dog, as she considered both she and the dog were working in consort, drawing on their human-animal bond, to strengthen Stephen's sense of wellbeing. The human-animal bond emerged as significant for this family in other ways too. The role of the dog with the remaining family is worthy of comment, as the dog seemed to be playing a part in assisting the family to grieve, and to move into a different phase in their lives. Michelle observed, that for the family (including their adult children in their mid-twenties still living at home): "I think [the dog] is replacing Stephen. He's helping the three of us at home, the children coping, and me coping. We've all become very attached to him". Michelle further reflected: So, it helps them too. Definitely. So, he virtually has not replaced Stephen, but they can, instead of being upset, they can cuddle [the dog] and interact. He has a special role for each one of us. He knows I'm, like, the mum, Stephen's the dad that I cuddle, L is his sister, so they'll cuddle a lot and L kisses them a lot, so they're snuggle bunnies, and D I'm allowed to play rough and play games with D. So, he has a role for each of us. Responses like this resonate with the discoveries of Ritchie et al. , who note that not only did the dogs reduce the stress of the carer's role, but also because (in the case of Michelle as a carer), the bond between the carer and the dog was "based on trust and appreciation of shared responsibility in the caring role". 3.2. Relationship Dynamic Relationship dynamics (i.e., the patterns of behavior between people and how they relate, interact and communicate with each other) varied, as already noted, across the 10 triads. These relationships often changed when the participant with YOD went into care, and this was commented on across all but one of cases of participants going into care full time. Before Cathy (CS#2) went into care, for example, her assistance dog Beth was largely treated as a pet in the home and was seldom in a harness. Once Cathy went into care, however, the dog was taken into the care facility nearly every day. Although Michael (Cathy's carer) noted that Cathy had deteriorated very rapidly, she still regularly asked for the dog, and Michael ensured that the dog and participant had the tactile contact that they both enjoyed. Michael described that "Beth [the dog] nuzzles up to her. Cathy tries to pet her, but she has no coordination. I take her hand and help her pet the dog. Beth sits at her feet". He also reported that other people in the care facility loved seeing the dog, and although she is not the only dog that visits: "they all love to see her, and she talks to them. Beth is delighted". For Michael, as a carer, this enabled a relationship dynamic between him and Cathy that had been lost when she was struggling at home with her dementia. Importantly too, for this family, the assistance dog provided family support in the transition process. Michael commented: "I have a 29-year-old daughter [who lives at home]. I think she has struggled seeing her mother decline. But she has a great rapport with the dog. Beth is a distraction when I look after her. The three of us sit in the courtyard in the sunshine. It's become part of the relationship". It was reported that the dog did her best work when Cathy went into care and the family was struggling emotionally to deal with the loss. This sort of shifting dynamic between dog and carers/family members was not uncommon across the project. As the program progressed, three participants moved from home into care. Subsequently, the assistance dog played some unexpected roles in supporting the family in the transition process. This was not possible in the case of Peter (the carer) (CS#1) having to return to work full time, which meant there would have been nobody home with the dog most of the time and consequently Aspen needed to be returned to the program. In the other two cases where the participant went into care (CS2 & #3), as reported by the family members, the dog played a significant role for the family both in connecting them to the participant and adjusting to their changing circumstances. Michelle (CS#3) for example, observed that with Stephen moving into full-time care, their relationship had changed for the better, following her difficulty in supporting his deteriorating condition, which included incontinence. She felt that at that point, she "sort of fell in a heap". With the additional support of the staff at the care facility, and the opportunity for Michelle to take over the management and responsibility of the dog, Michelle observed: "our relationship has completely changed again, like we're happy to see each other". As noted earlier, having the dog still living with them had an important impact on this family, as the dog appeared to be aware of the family's grief and provided each of the family members with individual support dealing with this, supporting the grieving process for the adult children in the family, as well as for Michelle. Ritchie et al. also noted in their project that the dog provided "a vital source of support to the spouse" when the partner passed away, facilitating the process of dealing with grief. 3.3. Responsibility for Caring The shared nature of the responsibility for caring between assistance dogs and family members providing support is particularly notable. Four family carers commented that the dogs maintaining a check on the participants with YOD provided reassurance to carers, and in three of these cases, they observed that they felt like they formed a care-giving team with the dog. Qualitative feedback from several of the carers confirmed they felt much greater confidence about the participants with dementia going out alone or being left alone in the house. This applied to both those participants who went into care during the program (specifically Sandra, Cathy, and Stephen), and those who stayed in the program, and in their homes, for the duration (Jason, James, Linda, Marcus, Cassie, Hugh, and Sandy). Others expressed this confidence in relation to leaving the home alone. When Lynette (CS#7) was first interviewed, she was very depressed about the wellbeing of Marcus, and her ability to provide him with the necessary support. They had only recently moved to the region, and at that stage did not know people who would visit regularly. She expressed hope that Marcus, who was a very shy man, would go out visiting once he had the dog, to help deal with his loneliness when she was at work. She explained why they moved to the island: "It was a place for Marcus to be happier in ... A place for Marcus to be safe. You know, if he does start losing his way, which he doesn't at all at the moment, it's an island ..." Lynette was lucid and reflective, and expressed her own sadness and grief, as well as reflecting on that of Marcus. She concluded: "And so I guess in terms of the dog, you know for me to know that he's got that company at home, and it's going to lessen his senses of grief and guilt and whatever." At the time of the second interview, Lynette observed: "I think they're doing very well together. They have a good bond". She also reiterated that Marcus and the dog spent considerable time having "long beach adventure walks" and noted that the three of them went to coffee shops and restaurants and went out visiting. When asked what was most important about Marcus having the dog, Lynette replied: "Look I think it's mostly companionship and confidence. Those two things". She added: "Well, I like the fact that when I go out to work that Marcus feels much more, much less lonely. Much more like he's got ... Having the dog has given him ... Sometimes gives him purpose, but also, it's just than companionship". Knowing that Marcus had this companionship and support had meant that Lynette's depression had decreased, because the bond between Marcus and the dog had relieved her of some of the responsibility of caring. Similarly, Sue (CS#5), who was still working three days a week, mentioned that she felt much safer about James out walking by himself, and being home alone when she was at work, now that he had the dog. In particular, she drew attention to the concern about James wandering out in front of cars when he went to cross the road, and she emphasized: "The biggest thing for me is that I know, I'm not worried when James is away from home", and she commented of George, the dog: "He's just such a blessing, such a blessing ... It gets him out and moving, it gives me security and confidence. I've cut down my hours, but I still work 3 days a week, so yeah, when I'm at work". In another case, Jeff (CS#6), for example, felt that prior to having the dog, he was uncertain about Linda going walking by herself to the supermarket, but she would now regularly go out shopping by herself, and return safely. By the end of the program, Jeff was so confident about Linda's ability to manage alone with the dog, that he was going away on overnight trips, and planning a fortnight away leaving Linda by herself. Linda was confident that she would cope, and Jeff felt she would too. Jeff observed with some relief that now he felt that he was not alone in doing the caring, and that rather being the two of them trying to manage day-to-day, they were now "a team of three". 3.4. Carer Wellbeing Of particular interest in this research was the impact of the presence of the assistance dogs on the wellbeing of the carers. While it was originally envisaged that this would be measured quantitatively, no clear consistent patterns were apparent in the data, possibly due to the heterogeneity of the families and their circumstances and the relatively small sample size. This reinforced the importance of the qualitative data and the narrative provided by the family carers to generate the insights needed to address this research question. This has important implications for the design and execution of future research in this area. The burden on carers emerged as an area that needed further consideration, with an evident risk of overloading family members and carers in some cases. The amount of available carer time and commitment was an issue raised by three of the carers who emphasized the demands of overseeing the care and maintenance of the dog. It was noted by some that the time and energy involved in participation in the program had not been part of the original briefing, and this was further exacerbated for those carers who were also working outside the home. The issue of keeping the house free of dog hair was raised frequently, and three carers also reported that taking the dog for long trips in the car was "more trouble than it was worth". Michelle (CS#3) observed that leaving the house with the dog was "like travelling with a baby because of all the equipment". Future programs need to ensure families are well briefed, especially where they might not have had previous experience of owning a dog. Veterinary and day-to-day costs were highlighted as an issue of wellbeing by several carers. At the time of this program, the Australian National Disability Insurance Scheme (NDIS) was not yet providing funding for assistance dogs for dementia participants. Being seriously out-of-pocket was of considerable concern, especially if providing care meant breadwinners were otherwise unable to work. Prescription foods, regular veterinary checks, vaccinations and so on proved costly, and medication and veterinary costs if the dog became ill sometimes proved to be prohibitive. In some cases, however, local veterinary practices chose not to charge at all for the care of assistance dogs. Lynette (CS#7) raised a concern about the accessibility of follow-up training when it was needed, or when they had questions about working with the dog. The paucity of available follow up appeared to impact her wellbeing. She described it as feeling "a little bit left", and suggested more regular contact with the dog trainer, as well as more frequent follow-up training, "especially in the first six months". She observed: "So, I know ... having the dogs for dementia is very new, but I think there are other programs with dementia dogs running and I'd be interested to know ... I knew there was no research. I just mean it would be interesting to see how similar or different the approach was from handing the dog over". The transition of participants with dementia into either respite or full-time care (CS#1, #2, & #3) required close liaison between the carers and the supporting organization and care facilities, and this proved to be an emotional burden for some carers. This is a new area of policy for many care facilities, and while some were well set up to have assistance dogs attend as part of respite care, others were very reluctant. Those that enabled the assistance dog to attend demanded a very high level of support from the carer as well as from the dementia support agency, but even with this support, it was found to be very problematic having the dog resident in the care facility. During this program, no dogs went into full-time care with their participant, but two attended on a regular basis at least several times a week, with the full-time attendance of the carer. Carer depression was noted as an issue that emerged regularly, but that was not necessarily evident consistently. The qualitative interviews suggested that the level of carer depression was tied much more to incidents related to the progression of dementia in their family members, than to the presence of the dog. Similarly, interviews suggested that sadness and grief were not necessarily consistently evident. This is something that warrants further exploration in carers of people with YOD. As Lynette (CS#7) noted: Obviously, the mental health of both of us is important, but what's behind that is a huge amount of grief, and loss and guilt. They all get thrown in together. The grief is huge ... there's all the plans that you had. There's both us having to leave jobs and friends behind ... He was teaching music. Instrumental teaching ... He misses playing and performing very much. So, you can talk about it in terms of depression and that kind of thing, and obviously depression can arise from all that, and has often done, but to me it's more layered and more complex. For most of the carers, this sense of loss was nuanced, but at times unmanageable, even with the support of the assistance dog. However, as Chris (CS#8) commented: "having the assistance dog is the best thing that has happened to us". 4. General Implications and Future Directions In this study, we investigated the impact of assistance dogs on family carers of people with YOD. Though the sample was relatively small, the data were collected over a two-year period and were rich and nuanced. These data reveal an important story of a diverse range of experiences; the good and the challenging. Many of the participants' experiences reflected and affirmed the findings of Ritchie et al. . This was particularly notable in the development of the human-animal bond, the relationship dynamics among the triads, the flexible nature of responsibility for caring, and the overall impact on carer wellbeing. Concerns were raised, however, by carers about the time and energy required of carers, and the financial impact of having an assistance dog (e.g., veterinarian expenses, grooming and food) in the absence of the support of a publicly funded scheme such as the Australian NDIS. When considering the placement of an assistance dog, it is not only the wellbeing of the primary owner that needs to be taken into consideration and that of the anyone who is likely to take on a primary care role, and as a consequence the care of the dog, but also importantly the wellbeing of the dog and the family's capacity to meet these needs . Furthermore, several cases in this study demonstrated the importance of sustaining the triadic relationship between the person with dementia, their carer and the dog when the person with dementia moved to out-of-home care. Regrettably, none of the dogs were able to transfer full-time to the out-of-home care facilities. In an effort to keep owners and their dogs together (or at least in regular contact) for as long as possible, this is a policy and practice issue that needs to be addressed by out-of-home / aged care facilities. A caveat of this research is the relatively small size of the sample. It also operated within a limited timeframe (albeit over two years). It would have been useful to be able to follow up the impact of the project on carers in the longer term. Additionally, it would have been useful to have further investigated how the assistance dogs managed both the demands of their working schedules on a long-term basis and the subsequent separation from their primary carer. Future research could investigate both the longer-term impact on carers and the longer-term wellbeing of the dogs (including their care and access to veterinary services, where dogs needed to be retired from the program or where they stayed with the family in the absence of their primary partner when the person with YOD needed to go into residential care or died). Since this project was completed, several participants with YOD have died, and others are now in long-term care. It would be valuable to have been able to formally follow up the impact of the assistance dogs on carers and families as circumstances changed over time. Anecdotally, Hugh died soon after the end of the study, and his assistance dog went to live with his son and grandchildren, as Hugh's partner/carer Marlene felt sad having the dog without Hugh. The dog had enabled the rebuilding of interactions between Hugh and his grandchildren, so the placement of the dog with them may well have enabled further family support. Similarly, Jason died (of an unrelated illness), but Annabelle chose to keep the dog with her as it provided her with great support and comfort. Despite its limitations, at the time of completion, this research project constituted the largest and longest project of its kind, and certainly the only one focusing on the circumstances surrounding assistance dogs for both people with YOD and their family carers. 5. Conclusions Trained assistance dogs can play an important role in promoting the health and wellbeing of people with YOD and that of their family carers, both in terms of hedonic wellbeing and eudemonic wellbeing. There is evidence of a strong human-animal bond not only between the assistance dog and the person with dementia, but also with the primary family carer and other family members. The relationship dynamics enabled and enhanced by the dog as part of the triad aided the carer in the practical execution of their role and in sustaining the wellbeing necessary for them to continue that role. Notably, our data suggests the positive effects of the relationship between the carer (and the wider family) and the assistance dog can continue beyond the move of the person with YOD into out-of-home care. However, support needs to be in place as the circumstances of the family member with YOD changes and the role and place of the assistance dog as part of a triad also changes. Policies need to be developed to support the dogs to have greater access to nursing homes, so they might continue a regular relationship with the person with YOD and thus continue to deliver on the benefits of the human-animal bond. Practical support with ongoing care of the dog, including follow-up from experienced trainers, and financial support of a scheme such as the Australian NDIS could also be important. Acknowledgments The authors wish to thank the individual participants for enabling this research to take place, and in particular acknowledging their willingness to have researchers visit their homes and to have shared their journey often at difficult times. The authors also acknowledge and thank the members of Dementia Australia's Young Onset Dementia Support Group for their contribution to the development of the research protocol and promoting the project. Author Contributions Conceptualization, K.R.M.; Methodology, K.R.M.; Formal analysis, G.M. and K.R.M.; Writing, K.R.M. and G.M.; Review and editing, K.R.M.; Project Administration, K.R.M.; funding acquisition, K.R.M. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement All procedures performed involving human participants were in accordance with the ethical standards of the institutional Human Research Ethics Committee (HREC), approval number 1647054 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The project was exempted from review by the host institution's Animal Research Ethics Committee. Informed Consent Statement Informed consent was obtained from all individual participants included in the study. Data Availability Statement Raw data not publicly available consistent with ethics approval. Inquiries to be directed to corresponding author, McVilly. Conflicts of Interest The authors confirm that there are no relevant financial or non-financial competing interests to report. 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PMC10000236 | A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity. LAT1 chemotherapy colorectal cancer comprehensive analysis tumor microenvironment JSPS KAKENHIJP 21K15925 This work was supported by JSPS KAKENHI Grant Number JP 21K15925 Grant-in-Aid for Early-Career Scientists. pmc1. Introduction Glucose and amino acid transporters are representative transporters that bring nutrients into cells . Among these, the large neutral amino acid transporter (LAT) plays a critical role in the cellular uptake of amino acids that are essential for human activity. Recently, it has been reported that the expression levels of the LAT family of proteins are correlated with cancer proliferation via mTOR pathway activation , angiogenic activity , and clinical prognosis in various carcinomas. LAT1 is strongly correlated with clinical prognosis and tumor-specific upregulation . Furthermore, it reportedly correlates with cisplatin resistance and is attracting attention as a therapeutic target and biomarker for biliary tract cancer and other cancers . LAT1 is expressed specifically in tumors and can be referred to as a "tumor cell type transporter", whereas LAT2 is mainly expressed in normal cells and can be referred to as "a normal cell type transporter." Since pan-LAT inhibitors also inhibit LAT2 simultaneously, their toxicity to normal cells has been reported . The association between LAT1 expression and prognostic factors in colorectal tumors and its association with proliferative potential in vitro using colorectal cancer (CRC) cell lines have been previously reported; however, the specific corresponding mechanisms of which have not yet been clarified . LAT1 inhibitors are unique agents that inhibit the growth of cancer cells. The pan-LAT inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which broadly inhibits LAT1-4, has mainly been used in previous reports, and its tumor growth inhibitory activity has been reported in vitro and in vivo in therapeutic experiments . However, because BCH also inhibits LAT family proteins other than LAT1, it is expected that LAT1 inhibitors will be superior to BCH in terms of fewer side effects. Recently, JPH203, a novel LAT1-specific inhibitor, was developed and reported to inhibit tumor growth . The high selectivity of JPH203 for LAT1 compared to that for BCH suggests that JPH203 is an effective drug with fewer side effects because it has less of an effect on normal tissues. Only one report directly compared BCH and JPH203 . This demonstrated the superiority of JPH203 by comparing both drugs in an in vitro experiment using an osteosarcoma cell line. Inhibition of LAT1, which has been reported to show tumor-dominant expression and an association with prognosis, is expected to suppress tumor progression by reducing tumor-specific amino acid uptake, leading to starvation, with minimal effect on normal cells. In this study, we aimed to elucidate the relationship between LAT1 expression and tumor progression and to investigate the anti-tumor effects and mechanism of LAT1 inhibition in CRC using clinical samples, in vitro and in vivo experiments, and comprehensive analyses of gene expression profiles. 2. Materials and Methods 2.1. LAT Expression Based on UCSC Cancer Genomics Browser Analysis UCSC Xena (accessed on 21 May 2020)) is a statistical mining tool used to explore functional genomic datasets for correlations between genomic and phenotypic variables . Using this platform, LAT1 expression in normal tissue and tumor tissues obtained from the colon and other organs was analyzed and evaluated in relation to the prognosis. The relative expression levels of LAT1 and LAT2 in the normal colorectal mucosa and colorectal tumors were also evaluated. 2.2. Patients In total, 154 consecutive patients with colon cancer who underwent surgical resection for CRC between 2013 and 2015 at Hiroshima University Hospital were enrolled. The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Hiroshima University Hospital (approval number [E2020-2051]). Although the Ethics Committee of Hiroshima University Hospital waived the requirement for informed consent because we used anonymized data, informed consent was obtained using an opt-out option. 2.3. Immunohistochemistry for LAT1 Expression in Human CRC Tissue To examine the proportion of LAT1 expression and its association with clinicopathological features, LAT1 immunostaining was performed in 154 surgically resected CRC specimens. Formalin-fixed, paraffin-embedded tumor tissues were cut into serial 4 mm sections and examined for LAT1 expression using immunohistochemistry. Staining intensity scores for LAT1 expression were evaluated as follows: 0, no staining; 1+, weak; 2+, moderate; 3+, strong reaction intensity. 2.4. Classification of Human Colon Cancer Tissue According to Microsatellite Status To examine the relationship between LAT1 efficacy and the microsatellite instability (MSI) status, CRC tissue samples were examined for the MSI status either by immunohistochemical staining for mismatch repair protein expression or by PCR amplification of microsatellite sequences using the resected specimens. MSI determination by PCR was performed using pentaplex PCR as described previously . 2.5. Evaluation of Human CRC Stromal Volume Formalin-fixed, paraffin-embedded tumor tissues were cut into serial 4 mm sections and immunostained with anti-vimentin antibodies to evaluate stromal volume in human CRC. After vimentin immunostaining, the proportion of vimentin-positive areas in the CRC was evaluated. The correlation between the number of vimentin-positive regions and LAT1 expression in CRC was also examined. Observations were made using a BZ-X710 all-in-one fluorescence microscope (KEYENCE, Osaka, Japan). Microscopic fields that included the foci were photographed at 400x magnification for each specimen and analyzed. All the micrographs were obtained under the same conditions (exposure time, gain, illumination light intensity, and aperture stop). The vimentin-positive areas were determined by arranging and quantifying the brightness thresholds using the BZ-H3C hybrid cell count application of the BZ-X analysis software, version 1.3.1.1 (KEYENCE). 2.6. RNA Extraction and Quantitative PCR to Evaluate LAT1 Expression in CRC Cell Lines As previously described , RNA extraction and quantitative PCR were performed using the RNeasy Kit (Qiagen), first-strand cDNA synthesis kit (Amersham Biosciences, Piscataway, NJ, USA), and LightCycler FastStart DNA Master SYBR Green I Kit (Roche Diagnostics, Basel, Switzerland). Reactions were performed in triplicate. To correct for differences in both RNA quality and quantity between samples, expression values were normalized to those of glyceraldehyde-3-phosphate dehydrogenase. Primer sequences were based on previous reports and are provided in Table S1. The relative LAT1 expression in each cell line was calculated according to the DDCT method, and the normal human/mouse colon mucosa was used as a control. 2.7. Cell Lines The Balb/c mouse colon cancer cell line CT26 was obtained from the American Type Culture Collection (Manassas, VA, USA). The human colon cancer cell lines DLD1, SW480, HCT116, KM12C, Lovo, HT29, WiDr, and Caco2 were obtained from the Health Science Research Resources Bank (Osaka, Japan), and KM12SM was kindly gifted by Dr. Isaiah J. Fidler (University of Texas, Austin, TX, USA). Balb/c mouse-derived mesenchymal stem cells (MSCs) were obtained from Cyagen Biosciences Inc. (Tokyo, Japan). 2.8. JPH203 Effects on Cancer Cell Proliferation In Vitro Cancer cells were maintained in Ham's F-12 Nutrient Mix medium (Life Technologies Corporation, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (Sigma-Aldrich, St. Louis, MO, USA) and penicillin-streptomycin mixture for in vitro experiments. Among human-derived 9 colon cancer cell lines (DLD1, SW480, HCT116, KM12C, Lovo, HT29, WiDr, Caco2, and KM12SM) and the mouse-derived colon cancer cell line (CT26), cell lines showing LAT1-high expression, as well as those showing LAT1-low expression, were used for the proliferation assay to evaluate the effect of JPH203 on LAT1 expression. Colon cancer cell lines (cell density, 6 x 104 cells per well) were seeded into 24-well plates (Essen ImageLock; Essen Bioscience, Ann Arbor, MI, USA). The cells were treated with various concentrations of JPH203. Growth curves were generated from a bright field image obtained using a label-free, high-content time-lapse assay system (Incucyte Zoom; E Essen BioScience, Ann Arbor, MI, USA) that automatically expresses cell confluence, as previously described . All experiments were performed in quadruplicate. 2.9. JPH203 Effects in CT26 and MSC Co-Culture System To distinguish CT26 from MSCs, green fluorescent protein (GFP) and puromycin resistance genes were transfected into CT26 colon cancer cells using copGFP control lentiviral particles (sc-108,084; Santa Cruz Biotechnology (Santa Cruz, CA, USA)) according to the manufacturer's protocol as previously described . The cells were maintained in a complete medium containing puromycin for two weeks after transduction. In the co-culture experiment, CT26-GFP and MSCs were maintained in RPMI1640 with 10% fetal bovine serum (Sigma-Aldrich, St. Louis, MO, USA), a penicillin-streptomycin mixture, and 1 ng/mL of fibroblast growth factor-2. CT26-GFP cells (cell density, 3 x 104 cells per well) cultured with MSCs (cell density, 3 x 104 cells per well) were seeded into 24-well plates (Essen ImageLock; Essen Bioscience, Ann Arbor, MI, USA). The cells were treated with JPH203 at a 1 mM concentration. The proliferation of CT26-GFP cells and MSCs was measured using a label-free, high-content time-lapse assay system (Incucyte Zoom; Essen BioScience, Ann Arbor, MI, USA). CT26 and MSCs proliferation abilities were calculated separately according to the difference in color. 2.10. Treatment Experiment Using JPH203 in an Orthotopic Implantation Tumor Model Female Balb/c mice were obtained from Charles River Japan (Tokyo, Japan). Animal experiments were approved by the Committee on Animal Experimentation at Hiroshima University (Approval number A20-26). Animal experiments were performed using the Balb/c mouse-derived CT26 CRC cell line with high LAT1 expression. As previously reported, CT26 alone transplantation forms stromal-poor tumors . Thus, we conducted animal experiments using a co-implantation model with cancer cells and MSCs in this study. MSCs are known to migrate to tumor sites and differentiate into carcinoma-associated fibroblasts (CAFs) upon interaction with cancer cells to form stromal-rich tumors . To reproduce the characteristics of stroma-rich colorectal tumors, 5 x 104 CT26 cells (stably expressing firefly luciferase) and 5x 105 Balb/c mouse-derived mesenchymal MSCs in 50 mL of Hank's balanced salt solution were co-transplanted into the cecal wall of mice to generate an allogeneic immune response and a stroma-rich CRC mouse model for treatment with JPH203. Starting 1 d after transplantation, mice were divided into two groups; one group received 1200 mg/kg/day sulfobutyletherb-cyclodextrin (SBECD) intraperitoneal injection (control group), and the other group received 50 mg/kg/day JPH203 intraperitoneal injection (treatment group). Orthotopically implanted tumor growth (CT-26/Luc cells) was monitored using bioluminescence imaging (BLI). BLI was carried out noninvasively on days 7 and 14 after treatment using a Lumina II in vivo imaging system (Xenogen, Alameda, CA, USA). After anesthetizing the mice with intraperitoneal anesthesia, 200 mL of D-luciferin was injected intraperitoneally into the mice (150 mg/kg), and images were acquired noninvasively . The experiment was continued for 14 days. On day 15, mice were euthanized and necropsied. 2.11. Necropsy Procedures and Histological Evaluation Mice with orthotopic tumors were euthanized, and their body weights were measured. Following necropsy, tumors were excised and weighed. Tumor volume was calculated as V = (W2 x L)/2 (V: volume, W: short diameter, L: long diameter). Regional (celiac and para-aortic) macroscopically enlarged lymph nodes were harvested, and histological analysis was performed to verify tumor metastasis. Tumor tissues were fixed with formalin-free zinc fixative (BD Pharmingen; BD Biosciences, CA, USA), paraffin-embedded, cut into serial 4 mm sections, and then examined by pathological and immunohistochemical evaluation. 2.12. Double Immunofluorescence for E-Cadherin and Vimentin Double immunofluorescence staining for E-cadherin and vimentin was conducted as previously reported using the Opal 4-color manual immunohistochemistry (IHC) kit (NEL810001KT; PerkinElmer). Observations were made using a BZ-X710 all-in-one fluorescence microscope (KEYENCE). Representative images were obtained from microscopic fields at 40x, 100x, and 200x magnification for each specimen. 2.13. RNA Sequencing and Gene Set Enrichment Analysis (GSEA) Orthotopically implanted tumors treated with JPH203 or SBECD were dissected and mechanically disrupted using a homogenizer. Total RNA was extracted from tissue homogenates using the Qiagen RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's protocol. Library construction and data processing were performed at Beijing Genome Institute (Beijing, China). The library was sequenced using the DNBSEQ-G400RS platform, and high-quality reads were obtained. Sequence alignment was conducted using the GRCm38 mouse reference genome version GCF_000001635.26_GRCm38.p6 (accessed on 10 March 2022)). The HOM_Mouse Human Sequence, downloaded from the Mouse Genome Informatics website (accessed on 19 May 2022)), was used to convert the mouse genes to human genes. After removing genes with FPKM = 0 from all samples, GSEA was performed as previously described to analyze the differential modulation of molecular pathways. 2.14. Functional Enrichment Analysis The differentially expressed gene (DEG) analyses of molecular pathways and gene ontology (GO) terms for cellular components were performed via Dr. Tom's web according to the path annotation classification from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and GO annotation classification, and the Phyper function in the R software was used for enrichment analysis. Upon calculating the p-value and false discovery rate correcting the p-value, the q-value was obtained, and a q-value of <0.05 was regarded as a significant enrichment. 2.15. Reagents JPH203 and SBECD were kindly provided by J-Pharma (Kanagwa, Japan). The primary antibodies used were as follows: monoclonal rabbit SLC7A5/LAT1 antibody NB100-734 from Novus Biologicals (Littleton, CO, USA), polyclonal rabbit E-cadherin antibody from Santa Cruz Biotechnology (Santa Cruz, CA, USA), and vimentin affinity-purified goat polyclonal antibody from Santa Cruz Biotechnology (Santa Cruz, CA, USA). 2.16. Statistical Analysis Clinicopathological features were analyzed using the kh2 test or Fisher's exact test to compare categorical data and Student's t-test or Welch's t-test to compare continuous data. In multiple comparisons for continuous data, one-way ANOVA was conducted. In the clinical data analyses, a post hoc power analysis was conducted to determine the power for the sample size. Spearman's rank correlation coefficient was used to index correlations. A log-rank test was used to compare the Kaplan-Meier curves and analyze overall survival. Statistical significance was set at p < 0.05. All statistical analyses were conducted using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan) . 3. Results 3.1. LAT1 Expression in Humans According to Database Analysis Using Xena In the database (GTEX and TCGA) analysis using the UCSC Xena platform, LAT1 expression in tumor tissues was markedly higher than that in normal tissues . Kaplan-Meier survival curves based on LAT1 expression in overall cancer showed that patients with high LAT1 expression had considerably poorer prognoses . LAT1 expression was higher in metastatic tumors, recurrent tumors, primary tumors, and normal tissues, in this order . The comparison of LAT1 expression according to cancer type revealed moderate-to-high LAT1 expression in CRC . Subsequently, an additional analysis was performed, focusing on LAT family expression in CRC. To confirm the specificity of LAT family gene expression in tumor tissues, we analyzed the expression levels of LAT family genes in normal and CRC tissues and found that the expression levels of LAT1 to LAT4 were similar in normal tissues, while LAT1 expression was clearly higher than that of LAT2, LAT3, and LAT4 in CRC tissues. This result indicates that LAT1 expression, but not LAT2, LAT3, and LAT4 expression, is dominant in CRC tissues . The Kaplan-Meier survival curves for CRC also showed that CRCs with higher LAT1 expression had a poor prognosis (p < 0.05) . In addition, a comparison of LAT1 expression in normal tissues and primary tumors in colon tissues showed that LAT1 expression was higher in primary tumors than in normal tissues . 3.2. Immunostaining in Human CRC Specimens Among 154 clinical CRC cases, LAT1 was positive in 68.8% of the cases, based on the scale shown in Figure 1h. LAT1 expression was evaluated by classifying LAT1 staining as 0, 1+, 2+, or 3+, with 0 and 1+ defined as negative and 2+ and 3+ as positive. LAT1 was positive in 68.8% of the cases. Post hoc power analysis of data from the 154 patients demonstrated a statistical power greater than 90% for LAT1-positive expression versus LAT1-negative expression (power = 0.99) for both subjective and objective evaluations. When comparing LAT1-positive and LAT1-negative patients, stage, T-classification, and N-classification were extensively higher in the LAT1-positive group. Other clinicopathological characteristics, such as sex, tumor location, histological type, budding grade, MSI, KRAS mutation, and BRAF mutation, were not significantly different (Table 1). 3.3. LAT1 Expression in Colon Cancer Cell Lines In human-derived 9 colon cancer cell lines (DLD1, SW480, HCT116, KM12C, Lovo, HT29, WiDr, Caco2, and KM12SM) and a Balb/c mouse-derived colon cancer cell line (CT26), LAT1 mRNA expression was high in HT29 and CT26 (relative expression: 17.8 and 22, respectively), intermediate in SW480 and HCT116, and low in DLD1 and Lovo (relative expression: 0.3 and 1.5, respectively). There was no significant difference in the LAT1 average expression between the MSS and MSI cell lines . 3.4. Proliferation Assay Using Colon Cancer Cell Lines with JPH203 In Vitro Using DLD1, Lovo, and SW480 as LAT1-low expression cell lines and HCT116, HT29, and CT26 as LAT1-high expression cell lines, we conducted in vitro experiments to evaluate the effect of JPH203. Each experiment was conducted with various concentrations of JPH203 in the range of 0-20 mM. The evaluation was performed by labeling the area of the cancer cell-occupying region and measuring the area using Incucyte Zoom (Ver. 2018A). As a representative example, the results for CT26 cells are demonstrated. All other cell lines were evaluated in the same manner. The results showed that JPH203 inhibited cell proliferation in a concentration-dependent manner, as shown in Figure 2c. This effect was pronounced when LAT1 expression was above a certain level. 3.5. JPH203 Administration Effect in a Congenic Mouse Tumor Model with Abundant Stroma A representative image of the tumors removed 14 days after transplantation is shown in Figure 3a. Luciferase activity in the tumors over time was measured and compared between the control and treatment groups. Luciferase activity was markedly lower in the treatment group than in the control group at 14 days post-transplantation . Images taken at sacrifice are shown in Figure 3c. Each group comprised 12 mice; however, one mouse in the treatment group showed no tumor incidence. Therefore, collectively, 12 tumors in the control group and 11 tumors in the treatment group were evaluated. The treatment group with JPH203 had an obviously reduced tumor size compared with that in the control group. A summary of the results from the 12 control and 11 treated animals is shown. Marked suppression of tumor weight, volume, and metastasis was observed in the treatment group (Table 2). 3.6. RNA Sequence To analyze the changes in gene expression profiles in mouse tumors induced by JPH203 treatment, RNA was extracted from orthotopically implanted tumors of mice in the control and treatment groups and analyzed using RNA sequencing. The significant DEGs detected were statistically plotted according to the gene expression level of each sample . JPH203 treatment upregulated 163 genes and downregulated 442 genes. A bubble chart of enrichment using the KEGG PATHWAY analysis is shown . The pathways with the highest variability were identified and classified. Remarkably, stroma-related pathways were greatly suppressed. Cancer growth pathways and amino acid metabolic pathways were also suppressed. In contrast, glutamine metabolism, which is a non-essential amino acid pathway, was activated. The results of the GO term analysis of the cellular components are shown in Figure 4c. The expression of genes related to the extracellular matrix was decreased. Similarly, in GSEA, the gene sets related to stromal responses were reduced. Proliferation-related gene sets were suppressed, consistent with previous reports. Amino acid-related gene sets were also suppressed, but the suppression of the stromal response was more remarkable . The results of RNA sequence analysis were validated in human specimens, mouse tumor tissues, and in vitro experiments. To validate the effect of tumor stromal suppression by JPH203 on RNA sequencing, immunohistochemical evaluation was performed on the mouse tumors. Evaluation with H&E staining of excised mouse tumors in the SBECD (control) group showed that the tumor exhibited infiltrative invasion and abundant stromal reaction. The co-implantation of CT26 and MSCs produced stroma-abundant tumors, as we expected. The tissue structure consisted of a mixed component of the epithelial phenotype area and mesenchymal phenotype with a spindle-shaped morphology area . In the group treated with JPH203, tumors developed expansively with poor stroma. The JPH203-treated group showed an epithelial phenotype and a homogeneous tissue structure with poor heterogeneity . The control group showed an abundant area positive for vimentin staining, a representative stromal marker, in the fluorescent double immunostaining of mouse tumors. Merged regions of E-cadherin and vimentin expression, indicating epithelial and mesenchymal transition (EMT), were broadly observed. In contrast, the JPH203 treatment group showed a poor stromal response, and the majority of tumors had an epithelial phenotype with dominant E-cadherin expression . The vimentin/DPAI-positive area rate was significantly lower in the JPH203 group than in the treatment group. The vimentin/E-cadherin-positive area rate was significantly lower in the JPH203 group than in the treatment group . We subsequently performed immunostaining for vimentin for validation in 154 human CRC tissue specimens and evaluated the stromal regions and quantified the occupied area, as shown in Figure 5e. Scatter plots for the LAT1 scores and vimentin area (area, %) are shown in Figure 5f. The LAT1 score was evaluated by immunostaining from 0 to 3+, according to the definition described in the Methods section. A correlation was observed between the LAT1 score and vimentin area, with higher LAT1 expression scores indicating higher vimentin expression. The correlation coefficient was 0.714, indicating a strong positive correlation. In vitro, JPH203 inhibited not only CT26 proliferation, but also MSC proliferation in an assay in which cancer cells (CT26) and MSCs were co-cultured . 4. Discussion In this study, we aimed to elucidate the relationship between LAT1 expression and tumor progression and investigate the anti-tumor effects and mechanism of LAT1 inhibition in CRC. LAT1 expression was higher in colorectal tissues than in normal tissues. LAT1 expression increases with tumor progression, and patients with abundant LAT1 expression have a poor prognosis. Immunostaining of CRC specimens revealed that 68.8% of cases showed LAT1 positive expression, which was dominant at the tumor site. In CRC cell lines, LAT1 was also highly expressed in most cell lines, compared to that in the normal mucosa. JPH203 effectively inhibited the proliferation of CRC cell lines and inhibited tumor growth and metastasis in a mouse model. Comprehensive analysis revealed the suppression of not only proliferative and amino acid metabolic pathways, but also stroma-related pathways upon the administration of an LAT1 inhibitor. Data-based analysis using UCSC Xena showed predominant expression of LAT1 compared to that of other LAT family members in various cancer types, and a similar trend was observed in CRC. These results were consistent with a previous report, which also found a correlation between LAT1 expression and CRC prognosis . The expression of LAT1 was higher in the following order: metastases, recurrent tumors, primary tumors, and normal tissues. This result suggests that it is a molecule involved in tumor progression and metastasis. It has been previously reported that LAT1 expression correlates with metastasis in CRC , and it is interesting to note that LAT1 is also highly expressed in recurrent tumors. In our study of clinical specimens, a similar correlation between LAT1 expression and tumor stage was confirmed. LAT1 is predominantly expressed in tumors of various carcinomas, including CRC . In contrast, LAT2 is expressed in normal tissues, such as renal epithelial cells, brain capillary endothelial cells, neuroendocrine cells , and the proximal tubules of the kidney ; however, few reports have evaluated LAT2 expression in human tissues. In our database analysis, only LAT1 expression was tumor-dominant, and LAT2, LAT3, and LAT4 were similarly expressed in tumor and non-tumor tissues. These results support the advantage of LAT1 specific inhibition. We evaluated LAT1 expression in multiple CRC cell lines. In most cell lines (9 of the 10 CRC cell lines), LAT1 expression was higher in cancer cell lines than in normal tissues. This suggests that LAT1 may serve as a potential therapeutic target. These results were almost consistent with a previous report that showed higher LAT1 expression in various cancer cell lines, such as HT29, than in normal tissue . We assumed that the effect of JPH203 was dependent on LAT1 expression; however, JPH203 was effective when LAT1 expression was above a certain level. The fact that JPH203 is a competitive inhibitor may be a contributing factor to this result. In the in vitro experiment using various cell lines, there was no clear difference in LAT1 expression or the effect of JPH203 depending on the MSI status. Similarly, there was no relationship between LAT1 expression and the MSI status in immunostaining studies of clinical specimens. Although the MSS status has been reported to be associated with resistance to immune checkpoint inhibitors and anticancer drugs such as 5-flurouracil , no clear relationship between the MSI status and the effects of LAT1 inhibitors was observed in this research. The IC50 of JPH230 in the CRC cell lines in our experiment was 2 to 10 mM , although the IC50 was higher than that of general chemotherapeutic agents, such as Paclitaxel (0.0000077 mM) and 5-FU (1.12 mM) . The IC50 of JPH203 for cell proliferation in the CRC cell line HT29 is reported to be 4.1 mM , which is similar to our observations. In the previous study, the plasm concentration of JPH203 was only 1000 ng/mL (approximately 2 mM), after administrating a clinically equivalent dose (25 mg/kg) of JPH203. However, the JPH203 administration exhibited 60-80% tumor growth inhibition against mouse tumors under in vivo conditions. These observations suggest that there may be some discrepancy between IC50 in plasma and in vitro conditions in JPH203 usage. The authors discussed that this discrepancy could be attributed to the difference in the substrate concentration (amino acid) between in vitro culture condition and plasma, given that JPH203 inhibits LAT1 by competing with its substrates. Furthermore, as conventional chemotherapeutic agents, such as Paclitaxel and 5-FU, exert cytotoxicity toward not only cancer cells, but also normal cells, untoward effects are unavoidable. In contrast, JPH203, despite its higher IC50, would be expected to exert weaker adverse effects on normal cells because of its higher cancer cell selectivity. These pharmacological properties could redeem the high IC50 of JPH203. In 2023, a phase 2 clinical study also showed effective results at a similar concentration of JPH203 . As the pharmacokinetics of this drug are inferred to be too complicated to be simply explained only based on blood concentrations, the detailed mechanism of pharmacokinetics is an issue to be addressed in future research. CRC has long been known to have abundant stroma ; however, in our previous study, tumors implanted with CT26 alone showed a poor stromal response in an orthoptic-implantation mouse model . We have previously reported that MSCs migrate to tumor sites and differentiate into CAFs through interaction with cancer cells; thus, co-transplantation of MSCs and cancer cells results in the formation of stromal-abundant tumors . Furthermore, co-implantation of MSCs with cancer cells by orthotopic implantation leads to the development of tumors with high-metastatic potential as we have previously reported . Based on these findings, in this study, we used an allogeneic immune-responsive, stromal-abundant, and highly metastatic colon cancer mouse tumor model created by orthotopic transplantation of CT26 and MSCs as a model that reflects the tumor microenvironment to evaluate the effects of drugs on the tumor microenvironment and metastasis. Histological and gene expression analyses performed in this study showed that JPH203 inhibited tumor stroma, amino acid metabolism, and proliferative pathways in allogeneic CRC lesions. These results are consistent with previous findings that JPH203 suppresses proliferative pathways, such as mTOR and amino acid metabolism , which is an intrinsic effect of the drug. Interestingly, while amino acid metabolism was suppressed, the metabolism of non-essential amino acids , such as glutamine, was activated, suggesting a compensatory effect for suppressing the essential amino acid pathway. In addition, there is a report showing that LAT1 is an essential molecule for the maintenance of the mesenchymal phenotype based on comprehensive analysis in in vitro experiments , but there have been few reports analyzing its value in vivo or in clinical specimens, a remarkable finding of this study. Other drugs with tumor-starving effects, such as glutaminase inhibitors and glucose transporter inhibitors, have also been reported to exert inhibitory effects on the stroma . Combining these previous reports and our results, we speculate that tumor starvation therapy may have inhibitory effects on EMT and tumor stromal activation. It is well known that the interaction between cancer and stroma plays an important role in the growth and metastasis of CRC . We focused on the interaction between cancer and stroma in the cancer microenvironment and showed that tumor stroma and stromal activation are associated with EMT in cancer progression, promoting tumor growth and metastasis . It is also shown that inhibiting cancer and tumor stroma is important for inhibiting tumor progression . In the clinical setting, the ability of LAT1 to inhibit both tumor cancer cell proliferation and stroma in colorectal tumors, which are considered to have abundant stroma, may be useful in inhibiting tumor progression. When using JPH203 in clinical practice, the possibility of causing side effects on normal stromal cells should be considered. However, immunohistochemistry of the clinical specimens in our study indicated that LAT1 expression on normal stromal cells is relatively low . It is possible that JPH203 dominantly inhibits tumor stroma with a mild side effect on normal stromal cells. The effect of JPH203 on normal stromal cells should be evaluated in future studies. In this study, we demonstrated the utility and mechanism of JPH203, a newly developed LAT1-specific inhibitor, to inhibit tumor progression using a unique stroma-abundant allogeneic immunoreactive mouse colorectal tumor created by the orthotopic transplantation of a mouse-derived CRC cell line and MSCs in the mouse cecum. The fact that JPH203 showed inhibitory activity not only on cancer cells, but also on the tumor stroma is considered an important finding and will be useful when considering its application to other stroma-abundant carcinomas and its use in combination with other drugs. This study has some limitations. First, animal experiments were performed using only one cell line, because there are only a few mouse-derived CRC cell lines that can be used in experiments to evaluate a therapeutic effect under allogeneic immune response conditions. Second, although our results showed that LAT1 inhibitors suppress tumor stroma, the mechanism by which amino acid transporter inhibition suppresses tumor stroma remains unclear and needs to be verified in further studies. 5. Conclusions LAT1 expression in CRC plays an important role in tumor progression. The LAT1 inhibitor JPH203 inhibits not only the proliferative pathway and amino acid metabolism, but also the tumor stromal reaction, and it may therefore serve as an effective novel therapeutic agent. Supplementary Materials The following supporting information can be downloaded at: Table S1: Primers used in this research. Click here for additional data file. Author Contributions Conceptualization: H.T. and R.Y.; methodology; H.T.; project administration: S.O. and S.T.; investigation: R.O., D.S., M.A., R.M., H.K., Y.H., R.H. and Y.U.; pathological analysis: A.I. and N.O.; writing--original draft preparation: R.O. and H.T.; writing--review and editing: R.Y.; supervision: Y.K., S.O. and S.T. All authors revised the manuscript, approved the manuscript to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Animal experiments were approved by the Committee on Animal Experimentation at Hiroshima University (Approval number A20-26). Informed Consent Statement The requirement for informed consent was waived by the institutional review board. Informed consent was obtained using the opt-out option. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Conflicts of Interest There are no conflict of interest to be declared for any of the authors. Figure 1 Database analysis based on UCSC cancer genomics browser analysis. (a) LAT1 expression in normal and tumor tissues (TCGA TARGET GTEx, 19,131 Samples). Welch's test was conducted. (b) The relationship between LAT1 expression and prognosis in Pan-Cancer (GDC Pan-Cancer, 9372 Samples). The cutoff was set at the median. A log-rank test was conducted. (c) LAT1 expression in normal tissue, primary tumor, recurrent tumor, and metastatic tumor (TCGA TARGET GTEx, 19,131 samples). (d) LAT1 expression according to the primary site of cancer (TCGA Pan-Cancer, 12,839 samples). (e) LAT family expression in normal tissue and colorectal cancer (GTEX, 9783 Samples; TCGA Colon Cancer, 571 samples). (f) Relationship between LAT1 expression and prognosis in colorectal cancer (GDC TCGA Colon Cancer (COAD), 571 Samples). The cutoff was set at the median. A log-rank test was conducted. (g) LAT1 expression in normal tissue, primary tumor, recurrent tumor, and metastatic tumor (colorectal cancer) (GDC TCGA Colon Cancer (COAD), 571 samples). (h) Immunostaining of LAT1 in surgically resected human colorectal cancer specimens. Figure 2 Expression of LAT1 in various cell lines, and the effect of the LAT1 inhibitor JPH203. (a) Relative LAT1 mRNA expression in colorectal cancer cell lines. * LAT1 expression was significantly lower compared to that in normal tissue (Student's t-test; p < 0.05). ** LAT1 expression was significantly higher compared to that in normal tissue (Student's t-test; p < 0.05). (b) The area of cells is evaluated upon its measurement using Incucyte. The upper panel shows the representative image of cancer cells labeled by the Incucyte software, whereas the lower panel shows the time-lapse image of CT26 cancer cell proliferation with and without JPH203 exposure (Drug concentration: 1 mM). (c) Inhibitory effect on cell proliferation by the LAT1 inhibitor JPH203. DLD1 was significantly more inhibited by JPH203 than by 20 mM (Student's t-test; p < 0.05). Lovo, SW480, HCT116, and CT26 were significantly more inhibited by JPH203 than by 1 mM (Student's t-test; p < 0.05). HT29 was significantly more inhibited by JPH203 than by 5 mM (Student's t-test; p < 0.05). Figure 3 Effect of JPH203 on orthotopic implanted tumor (Control group; n = 12 vs. JPH203 treatment group; n = 11). (a) Representative image of tumor obtained by luminescence observation (Days 7 and 14 post-transplantation). (b) Quantification of changes over time according to luminous intensity. Student's t-test was conducted for statistical analysis. (c) Macroscopic images of mouse tumors after sacrifice on day 14 post-transplantation. Figure 4 RNA extraction from a CT26 + MSC mouse cecal orthotopic tumor with and without JPH203. (a) Statistics of differentially expressed genes (DEGs). According to the gene expression level of each sample, the significant DEGs detected were statistically plotted. (b) Bubble chart based on KEGG pathway enrichment analysis. (c) GO cellular component enrichment bubble chart. (d) Gene set enrichment analysis (GSEA). Figure 5 Validation for results of RNA sequences with mouse tumor, human specimens, and in vitro analysis (a) Histological analysis of CT26 + MSC mouse cecal orthotopic tumor without JPH203. Control tumor showing infiltrating invasion manner (left and middle panels). Control tumor consists of a mixed component of epithelial phenotype and mesenchymal phenotype (right panel). Epi.; Epithelial phenotype (cobblestone shape), Mes.; Mesenchymal phenotype (Spindle shape). (b) Histological analysis of a CT26 + MSC mouse cecal orthotopic tumor with JPH203 (H&E staining). JPH203 showed expanding invasion manner (left and middle panels). Tumor treated with JPH203 consists of homogeneous type component showing epithelial phenotype (right panel). (c) Double fluorescence staining using tissue obtained from mouse orthotopic colon tumors. Expression of E-cadherin (red) and vimentin (green) in tumors generated by co-implantation of CT26 cells and MSCs. DAPI nuclear staining is shown in blue. The left panels show the control group, whereas the right panels show the JPH203 treatment group. First line represents merged images (x40), second line represents DAPI image (x100 and x200), third line represents E-cadherin (red) images (x100 and x200), fourth line represents vimentin (green) images (x100 and x200), and fifth line represents merged images (x100 and x200). (d) The quantitative data for double fluorescence staining. The E-cadherin/DAPI-positive area rate (upper graph). The Vimentin/DAPI-positive area rate (middle graph). The vimentin/E-cadherin-positive area rate (lower graph). Student's t-test was conducted for statistical analysis. (e) Immunohistochemistry for vimentin in surgically resected human colorectal cancer specimens. The left panel shows the H&E staining image with immunohistochemistry for vimentin. The vimentin-positive areas were determined by arranging and quantifying the brightness thresholds using the BZ-H3C hybrid cell count application of the BZ-X analysis software, version 1.3.1.1 (KEYENCE) (right panel). (f) Scatterplot for LAT1 expression and vimentin (Spearman's rank correlation was conducted to examine the correlation). (g) Inhibitory effect on cell proliferation by the LAT1 inhibitor, JPH203. Left panel shows the inhibitory effect of JPH203 on CT26 cells in the co-culture condition of CT26 and MSCs. The right panel shows the inhibitory effect of JPH203 on MSC under co-culture conditions of CT26 and MSCs. Student's t-test was conducted for statistical analysis. cancers-15-01383-t001_Table 1 Table 1 Association between LAT1 expression and clinicopathological features of human colorectal cancers. LAT1 Expression Positive Negative p * Number of patients 106 (68.8) 48 (31.2) Age (years) 68.8 +- 12.0 66.3 +- 11.9 0.222 Sex Male 65 (61.3) 26 (54.2) 0.480 Location Right side colon 34 (32.1) 20 (41.7) 0.277 Left side colon 72 (67.9) 28 (58.3) Histological Type tub1/2 95 (89.6) 44 (91.7) 0.778 Por/muc 11 (10.4) 4 (8.3) Stage I/II 46 (43.4) 32 (66.7) 0.009 III/IV 60 (56.6) 16 (33.3) T 1/2 26 (24.5) 22 (45.8) 0.014 3/4 80 (75.5) 26 (54.2) N N0 48 (45.3) 32 (66.7) 0.015 N1/2/3 58 (54.7) 16 (33.3) M 0 85 (82.3) 42 (79.4) 0.361 1 21 (17.7) 6 (20.6) Budding grade 1 21 (50.0) 9 (37.5) 0.732 2, 3 21 (50.0) 15 (62.5) Microsatellite instability MSS 98 (92.5) 43 (89.6) 0.545 MSI-high 8 (7.5) 5 (10.4) KRAS mutation + 42 (39.6) 19 (39.6) 1 BRAF mutation + 2 (1.9) 4 (8.3) 0.076 Data are represented as n (%). * kh2 test and Student's t-test were conducted for categorical and continuous data, respectively. cancers-15-01383-t002_Table 2 Table 2 Results of animal experiments (orthotopic implanted tumor). Group Tumor Incident Body Weight -Before (g) Body Weight -After (g) Tumor Weight (g) Tumor Volume (mm3) Lymph Node Metastasis Control (n = 12) 12/12 21.9 (21.0-23.5) 20.7 (19.0-21.2) 1.15 (0.27-1.58) 312.2 (108-650) 7/12 JPH203 (n = 11) 11/11 22.1 (21.5-22.8) 20.4 (18.1-22.6) 0.17 (0.15-0.27) 44.5 (32-108) 1/11 p-value * 1.00 0.37 0.49 <0.001 <0.001 0.027 * Fisher's exact test and Student's t-test were conducted for categorical and continuous data, respectively. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000237 | The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of our study was to retrospectively analyze 45 cases of canine and 47 cases of feline NSL and compare our results with previously reported data, also providing an extensive literature review. Breed, age, gender, clinical signs, type, and neurolocalization were recorded for each case. The pathological patterns and phenotype were assessed by histopathology and immunohistochemistry. The occurrence of central and peripheral NSL was similar between the two species in both primary and secondary types. NSL occurred with a slightly higher prevalence in Labrador Retrievers, and spinal cord lymphoma (SCL) was associated with young age in cats. The most frequent locations were the forebrain in dogs and the thoracolumbar segment in cats. Primary central nervous system lymphoma (CNSL) in cats most frequently involved the forebrain meninges, particularly as a B-cell phenotype. Peripheral NSL mostly affected the sciatic nerve in dogs and had no preferred location in cats. Nine different pathological patterns were identified, with extradural as the most prevalent SCL pattern in both species. Finally, lymphomatosis cerebri was described for the first time in a dog. cats central nervous system lymphoma dogs phenotype pathological pattern peripheral nervous system lymphoma This research received no external funding. pmc1. Introduction Primary central nervous system lymphoma (CNSL) is a relatively uncommon form of tumor in dogs and is rare in cats, accounting for approximately 4% of all canine lymphomas and less than 3% of cats with primary CNS tumors . Lymphoma within the CNS develops most commonly as part of a multicentric process in both species with a reported prevalence up to 12% or even nearly 30% in dogs, and 7.8% to 14.4% in cats. CNSL is believed to be more common in adult dogs with a mean age of onset of 7.4 years (range 3-11). Although there is no breed predisposition, Rottweiler dogs seem to have a slightly higher risk of developing CNS lymphoma . The mean age of cats with prevalent location in the spinal cord is reported to be 6.3 years (range 2-8) and no breed prevalence is recognized, with domestic shorthair cats being the most represented . Peripheral nervous system lymphoma (PNSL) is less commonly encountered than CNSL. In dogs, it is mostly secondary , whereas in cats the primary type is most frequently recorded and is considered the most common secondary tumor involving the PNS . However, the incidence of both CNS and PNS lymphoma may vary depending on the tumor location in the neuraxis and spinal and cranial nerves . The phenotype in canine CNSL is almost equally represented between B-cell and T-cell , and less than 4% are reported as non-B non-T cell. B-cell lymphoma, especially diffuse large B-cell lymphoma, predominates in secondary types . In cats, B-cell lymphoma is more frequently detected than T-cell lymphoma . Studies reporting a consistent number of cases with detailed neurolocalization and lesion distribution, as well as pathological patterns and immunophenotyping, are limited, with most of the existing literature being represented by case reports with fragmented information and therefore not always comparable. Given the lack of consistency in the evaluation of nervous system lymphoma in previous studies, the aims of this retrospective study were to determine the specific location, pathological patterns, phenotype, and prevalence of primary versus secondary, central and peripheral nervous system lymphomas in dogs and cats, evaluating 92 cases and comparing the results with the available literature. 2. Materials and Methods 2.1. Caseload Ninety-two cases of central and peripheral nervous system lymphoma diagnosed between 1994 and 2022 (45 in dogs and 47 in cats) were retrieved from the archive of the Neuropathology Laboratory of the Department of Veterinary Sciences of Pisa University. Signalments including breed, age, gender, main neurological signs, and tissue sample origin (biopsy or necropsy) are reported in Table 1. Specimens were obtained either from surgical biopsy or post-mortem examination and routinely formalin-fixed and paraffin wax-embedded and processed for histology. For each case, the type (primary or secondary/multicentric), the anatomical sites (intracranial, intraspinal, cranial, and spinal nerves), and the precise location and distribution were also recorded. In primary neoplasia cases, the extra-neural system involvement was assessed clinically or after complete post-mortem examination in case of death, as previously reported by other authors . 2.2. Histopathology and Immunohistochemistry Four-mm tissue sections were stained with hematoxylin and eosin (H&E), Luxol fast blue, and immunohistochemical methods. The histological classification and grading of the tumors were assessed according to the World Health Organization criteria . Immunoperoxidase was performed using a rabbit polyclonal antibody anti-human-CD20 (1:200, Thermoscientific, Fremont, CA, USA) and a rat monoclonal antibody anti-human-Paired Box 5 (PAX5, 1:250, Abcam, Cambridge, MA, USA) as B-cell markers, and a rabbit polyclonal antibody anti-human-CD3 (1:200, Dako, Glostrup, Denmark) as T-cell marker. Antigen retrieval for CD3 and PAX5 was performed by heat-induced epitope retrieval in citrate buffer at pH 6.0. No retrieval was performed for anti-CD20 antibody. Sections were pretreated with 1% H2O2 in PBS for 10 min to quench endogenous peroxidase activity, then rinsed with 0.05% Triton-X (TX)-100 in phosphate-buffered saline (PBS) (3 x 10 min) and blocked for 1 h with 5% normal horse serum (PK-7200, Vector Labs, Burlingame, CA, USA) in PBS. The sections were then incubated overnight at 4 degC in a solution of the antibodies with 2% normal horse serum and 0.05% TX-100 in PBS. Sections were then rinsed in PBS (3 x 10 min), incubated for 20 min with universal biotinylated anti-mouse/rabbit IgG (Vectastain Kit, PK-7200, Vector Labs), and then with ABC reagent (Vectastain Kit, PK-7200, Vector Labs). Sections were again rinsed in PBS (3 x 10 min). The immunoreactivity was detected by the streptavidin-biotin peroxidase method (Streptavidin Peroxidase, ThermoFisher Scientific, Fremont, CA, USA), using 3,3'-diaminobenzidine as chromogen. Negative controls were obtained by replacing the primary antibody with an irrelevant, isotype-matched antibody and with an anti-serum. Canine and feline normal lymph nodes were used as positive control. 2.3. Pathological Patterns Based on the histopathological location and distribution, the tumors were divided into the following pathological patterns: intraparenchymal mass (IP) (or intramedullary when in the spinal cord; IM), extraparenchymal (comprising both meningeal masses and leptomeningeal lymphomatosis; MM and LL, respectively), intravascular (IVL), lymphomatosis cerebri (LC), extradural (ED), intradural-extramedullary (ID-EM), and involving cranial and/or spinal nerves. In this latter condition, the term neurolymphomatosis (NL) was adopted, based on the presence of an infiltrating monomorphic population of malignant lymphoid cells within the endoneurium and perineurium of peripheral nerves . To compare our results with the literature, we grouped the affected nerves in four compartments: (1) cranial nerves; (2) brachial plexus and/or its branches; (3) spinal roots, spinal nerves, and spinal ganglia; and (4) sciatic plexus and/or its branches. Additional localization of neoplastic cells included choroid plexus, pituitary gland, and surrounding soft tissue of spinal cord and nerves. 3. Results Dogs affected by lymphoma had a mean age of 6.8 +- 3.8 years (ranging from 10 months to 14 years). There were 24/45 (53.3%) males and 21/45 (46.7%) females. Ten dogs were mixed breed, while the remaining were pure breed, namely Labrador Retriever (n = 5), Boxer (n = 4), German Shepherd (n = 3), Cane Corso (n = 3), Border Collie (n = 2), Hound (n = 2), Rottweiler (n = 2), and one of each of the following breeds: Epagneul Breton, Golden Retriever, Shih-tzu, Bulldog, West Highland White Terrier, Yorkshire Terrier, Dachshund, Beagle, Staffordshire Terrier, Bergamasco Shepherd, English Cocker Spaniel, Amstaff, Great Dane, and Pointer. Cats affected by lymphoma had a mean age of 8.3 +- 4.4 years (ranging from 3 months to 15 years). There were 22/47 males (46.8%) and 25/47 females (53.2%). Most of the cats were European Shorthair (n = 40), while the remaining seven cats belonged to the following breeds: Persian, Ragdoll, Maine Coon, Norwegian Forest Cat, Carthusian, Siamese, and European Longhair. The type, anatomical site, location, distribution, pathological pattern, nuclear size, grading, and immunophenotype of the lymphomas affecting the 92 animals are summarized in Table 2. In dogs, 22/45 (48.9%) lymphomas were intracranial, 14/45 (31.1%) were located within the spinal canal, and 9/45 (20%) were limited to the peripheral nervous system (PNS). In four cases, a simultaneous CNS and PNS involvement was observed. In cats, 24/47 (51%) lymphomas were located intracranially, 21/47 (44.7%) in the spinal canal, and 7/47 (14.9%) in the PNS. Within these cases, in three cats lymphoma was detected both in the brain and spinal cord, and in another two cats in the brain together with cranial and spinal nerves. A total of 24/45 (53.3%) canine lymphomas were classified as primary forms, and 21/45 (46.7%) had multicentric involvement. In cats, 27/47 (57.4%) and 20/47 (42.6%) lymphomas were classified as primary and multicentric forms, respectively. Regarding the phenotype, the majority (24/45; 53.3%) of canine lymphomas had a B-cell phenotype, while 15/45 (33.3%) a T-cell phenotype, and 6/45 (13.4%) were non-B non-T cell lymphoma. In feline lymphomas, 25/47 (53.2%), 18/47 (38.3%), and 4/47 (8.5%) had B-cell, T-cell, and non-B non-T cell phenotypes, respectively. 3.1. Intracranial Lymphoma The 27% (6/22) of canine and 20.8% (5/24) of feline intracranial lymphomas consisted of an intraparenchymal neoformation primarily but not exclusively located in the forebrain in both species , and mostly as part of multicentric lymphoma in both dogs (five out of six; 83.3%) and cats (three out of five; 60.0%). Grossly, focal or multifocal, whitish-grey masses accompanied by swelling of the peritumoral parenchyma and occasionally hemorrhagic areas were observed. The histopathological pattern was characterized by dense sheets of perivascularly arranged malignant cells that invaded the surrounding neuroparenchyma, creating highly cellular areas . In one cat (#46), the neoplastic infiltration involved both the optic nerves and extended into the diencephalon. B-cell, T-cell, and non-B non-T phenotypes were observed in both species. In dogs, four out of six (66.7%) cases were B-cell, one out of six (16.7%) was T-cell, and one out of six (16.7%) was non-B non-T cell lymphoma. In cats, three out of five (60.0%) were T-cell and two out of five (40.0%) were B-cell lymphomas. In one dog (#39), there was a grayish discoloration of large areas of the telencephalic white matter associated with bilateral loss of distinction between gray and white matter . Moreover, there was a blurring appearance of the hippocampal layers and cerebral sulci. No space-occupying lesions were detected in any areas of the brain. Histopathologically, the neoplastic cells diffusely infiltrated the white matter tracts and the perivascular spaces and showed large, round nuclei with a thin rim of slightly eosinophilic cytoplasm. Anisokaryosis was moderate with two to three mitoses for high power field (HPF, 400x, 2.37 mm2), and apoptotic figures were observed. Frequently, neurons were normal, even if extensively surrounded by neoplastic cells. Most malignant cells were positively immunolabelled with anti-CD3 marker and a small number of CD20-positive B-lymphocytes were observed within the perivascular cell infiltrate . Within the most severely affected areas, there was activation and proliferation of microglial cells. The morphological features of this case were consistent with lymphomatosis cerebri (LC). Almost half of the canine intracranial lymphomas (10/22; 45.4%) occurred as intravascular lymphoma (IVL), characterized by aggregation of neoplastic cells within the blood vessel lumen and scant invasion of the surrounding neuroparenchyma . Multifocal thrombosis, hemorrhage, and necrosis of different regions of the brain were consistently associated with IVL. Detailed features of these 10 cases were reported in a previous study . Intracranial lymphomas were characterized in many cases by prominent meningeal involvement, resulting in an extra-axial location (extra-axial lymphoma, EAL). Meningeal lymphoma was detected in 15/24 (58.3%) cats and in 2/22 (9.1%) dogs. These two canine tumors were multicentric, while 9/15 (60.0%) of feline cases were primary. This pathological pattern appeared as a well-defined, focal, irregular mass within the leptomeninges, resulting in a space-occupying lesion with compression of the underlying nervous tissue . The cells exhibited mild to severe pleomorphism and typical lymphoid appearance. In most cases, despite well-defined margins, the meningeal masses were found in association with perivascular aggregates of neoplastic lymphoid cells within the neuroparenchyma, showing an intraparenchymal pattern. Both B-cell and T-cell phenotypes were observed in the two canine tumors. In cats, 9/15 of lymphomas had a B-cell phenotype (60.0%), whereas 4/15 (26.7%) and 2/15 (13.3%) showed a T-cell and non-B non-T phenotype, respectively. With regard to location, all feline tumors involved the forebrain, mainly the leptomeninges of the frontal lobes. Additionally, in two feline cases, the meningeal masses were associated with an intradural-extramedullary (#77) and an extradural (#79) spinal cord lymphoma. Four cases of leptomeningeal lymphomatosis (LL) were observed; two were in dogs and two were in cats. In this pattern, neoplastic lymphocytes showed widespread diffusion predominantly within the subarachnoid space, infiltrating in some cases the subpial neuroparenchyma and perivascular spaces . The canine forms were a multicentric T-cell lymphoma affecting the brain (#40) and a multicentric B-cell lymphoma restricted to the spinal cord (#35). The feline forms were a primary T-cell intracranial neoplasia (#88) and a multicentric B-cell lymphoma affecting both the brain and the spinal cord . 3.2. Intraspinal Lymphoma Extradural (ED) and intramedullary (IM) pathological patterns of spinal cord lymphoma (SCL) were observed in both species. A total of 81% (17/21) of all feline SCL described in this study were ED lymphomas, represented by 47% (8/17) primary lymphomas and 53% (9/17) multicentric. The thoracolumbar segment was most affected (10 cases), including one cat (#79) with multifocal meningeal involvement of the brain and thoracic spinal cord. Canine ED lymphoma was recorded in 9/14 (64.3%) of all canine SCLs. A total of 33.3% (three out of nine) were primary, while 66.7% (six out of nine) were multicentric. The lesions were usually non-encapsulated, poorly defined, soft, grayish masses within the epidural fat, often with secondary severe spinal cord compression . In some cases, the tumor infiltrated and invaded the adjacent vertebral bodies or soft tissues. The meninges and spinal cord parenchyma were focally invaded. Most of the diffuse neoplastic infiltration in the epidural fat was composed of large, rounded to oval lymphoblastic cell sheets . B-cell lymphoma was the most frequently observed phenotype in primary types, both in dogs (three out of three; 100%) and in cats (six out of eight; 75.0%). As for secondary extradural lymphomas in dogs, four out of six (66.7%) were B-cell and two out of six (33.3%) were T-cell lymphomas. In cats, five out of nine (55.6%) were B-cell and four out of nine (44.4%) were T-cell. Intradural-extramedullary lymphoma was observed in only three (3/21; 14.3%) feline cases, either as a primary or multicentric form. They were all T-cell lymphomas located in the thoracolumbar segment. One of them was associated with a cerebral meningeal mass (#77). In one dog (#35), diffuse intradural-extramedullary neoplastic infiltration was observed throughout the entire spinal cord, showing a pattern consistent with LL. Intramedullary lymphoma was recorded in 4/14 (28.6%) of canine cases. Two intramedullary tumors were primary lymphoma B-cell and non-B non-T cell phenotypes, and two multicentric lymphomas showed sciatic nerve involvement and lumbosacral intra-medullary invasion (#5 and #9). A primary, non-B non-T cell lymphoma was observed in only one cat (#65). 3.3. Peripheral Nervous System Lymphoma Lymphoma of the peripheral nervous system (or neurolymphomatosis, NL) was observed in 13/45 dogs (28.9%), in two of which it was associated with an intracranial mass and one with concurrent spinal cord neoplasia. Of these cases, 7/13 (53.8%) were males and 6/13 (46.2%) were females. The mean age of dogs with NL was 7.4 +- 3.1 years (ranging from 2.5 to 14 years). There was no breed prevalence: four dogs were mixed breed, and the remaining dogs belonged to the following breeds: Great Dane, Hound, Golden Retriever, Bulldog, Staffordshire Terrier, Amstaff, Cane Corso, Rottweiler, and Labrador Retriever. Eight out of 13 cases (61.5%) were primary lymphomas, while the remaining 5/13 (38.5%) were multicentric. As for neurolocalization, in 7/13 (53.8%) cases the tumor involved the sciatic nerve and/or its branches, in 4/13 (30.8%) cases the spinal roots, spinal nerves and spinal ganglia (i.e., L1, L5, L6 nerves and one case multiple nerves), while in the remaining two cases (15.4%) it involved the trigeminal nerves . Histopathologically, NL was characterized by widespread infiltration of malignant lymphoid cells within the endoneurium and perineurium . By immunohistochemistry, 6/13 (46.2%) cases were T-cell lymphomas and 7/13 (53.8%) were B-cell lymphomas. In the feline cases, NL was detected in 7/47 (14.9%) cases, two of which were associated with an intracranial mass. Of these cases, three out of seven (42.9%) were males and four out of seven (57.1%) were females. The age of cats with NL varied widely, ranging from 3 months to 14 years; there was no breed prevalence, as four cats were European Shorthair and the remaining were a Ragdoll, a Carthusian, and an ELH cat. Five out of seven cases (71.4%) were primary lymphomas. As regards the localization, in two cases (#82 and #89) the neoplasm involved both the cranial and spinal nerves. Looking at each compartment individually, in three cases the neoplasm involved the sciatic plexus and/or its branches, and the same occurrence was recorded for spinal roots, spinal nerves, and spinal ganglia. In two cases, NL was observed in cranial nerves, and in another two cases the brachial plexus and/or its branches were involved. By immunohistochemistry, four out of seven (57.1%) cases were B-cell and three out of seven (42.9%) were T-cell lymphomas. 4. Discussion In our study, nervous system lymphoma occurred at any age in dogs and cats, from 3 months to 15 years, but was most common in middle-aged animals, as previously described . Similarly, our results support that there is no breed or gender predisposition, except in dogs, where five (11%) Labrador Retrievers were affected. Neurological signs were present in each patient and were highly variable, depending on the anatomical location of the tumor . Both peripheral and central nervous system involvement were identified, and nine different pathological patterns of nervous system lymphoma (intraparenchymal mass, lymphomatosis cerebri, intravascular lymphoma, meningeal mass, leptomeningeal lymphomatosis, extradural, intradural-extramedullary, intramedullary, and neurolymphomatosis) were recorded and will be discussed in this section. 4.1. Intracranial Lymphoma Intracranial lymphoma can involve the brain parenchyma and/or meninges as focal, multifocal, diffuse, and intravascular lesions, showing different histopathological patterns. 4.1.1. Intraparenchymal Patterns Intraparenchymal lymphomas (IPLs) are commonly reported in feline nervous system lymphomas and less frequently in the canine counterpart as either primary or multicentric types . There are currently insufficient data to support a different localization between primary and multicentric tumors; therefore, a thorough post-mortem examination remains mandatory to distinguish these two forms . Rostrotentorial regions such as the cerebral cortex , diencephalon , and the olfactory bulb are the most targeted brain sites. Although considered rarer, cerebellar location has also been described . In our study, canine IPL was observed in the occipital lobe, ponto-cerebellar angle, basal nuclei, thalamus, and parieto-occipital lobe with trigeminal nerve involvement. In cats, no preferred sites were identified, with both the forebrain and hindbrain regions involved. IPLs were mainly multicentric, and no breed or gender predisposition was identified in both species. The mean age of the dogs of our study was 6.8 years, in accordance with previously reported data (from 5.5 to 7.4 years) . As noted in this study, where the mean age at diagnosis was 10 years, affected cats are usually reported to be adult or elderly . The distribution of neoplastic cells and the invasion of the neuroparenchyma were similar to those reported in the literature . Lymphoma is usually composed of heterogeneous soft tissue with a whitish-gray appearance and is occasionally associated with small malacic foci . Adjacent tissue may be swollen, and multifocal lesions are described . Both T-cell and B-cell CNSLs have been described in the literature as in this study. 4.1.2. Lymphomatosis Cerebri The term "lymphomatosis cerebri" (LC) is used to describe an atypical neuroanatomical pattern of lymphoma cell spread . This variant is not so uncommon in the feline species . The absence of a cohesive mass is the most notable histological feature of LC. Lymphoid cells spread widely and diffusely mainly within the cerebral white matter from the frontal lobe to the brainstem and spinal cord . Focal leptomeningeal congestion and dilation of the lateral and third ventricles and central canal have also been described . Feline LC is always described as a T-cell primary form, although large granular T-cell lymphoma, presumably originating in the alimentary tract with a secondary diffuse infiltrate in the white matter of the brain, has been reported . No breed, age or gender predisposition has been identified . In human medicine, no differences in the distribution ratio between sexes have been reported and B-cell LC account for most cases . There are no reports of LC in dogs in the veterinary literature. In our case series we described a novel finding of a primary and diffuse infiltration of neoplastic T-cells within the white matter and leptomeninges in one dog that was consistent with LC. No cases of LC in cats were observed in our study. 4.1.3. Intravascular Lymphoma Intravascular lymphoma (IVL), also known as "angiotropic lymphoma", is a rare type of lymphoma that has been reported in both humans and animals . This form is characterized by the predominant growth of neoplastic cells within the lumen of blood vessels with little or no extension into the neuroparenchyma. Progressive occlusion of blood vessels with neoplastic cells leads to thrombosis, hemorrhage, and infarction. Various organs could be affected , but nervous system involvement is the most frequently reported in the literature, both in humans and domestic animals . In dogs, IVL has been described in 10 reports including a total of 51 dogs . In those IVL cases, there was either a restricted involvement of the brain or it was part of a multiorgan/multicentric IVL form. In our study, 10 cases of IVL were observed, representing almost half of the canine intracranial lymphomas. Affected animals were middle-aged dogs with a mean age of 8 years (ranging from 2.5 to 13 years), slightly above what was previously described in two studies (mean age of 7.25 and 6, respectively) . In accordance with the literature, no breed or sex predilection was observed in our cases. Although reported in previous studies , no spinal cord involvement was detected in our IVL cases, where the lesions were restricted to the brain. The histopathological lesions observed in the affected brain regions were similar to the ones described in previous studies on canine IVL . In our cases, the non-B non-T phenotype was identified in four IVL cases with a prevalence similar to that reported in a previous study . Although the T-cell IVL phenotype was the most prevalent in previous studies , in our remaining six cases there was an equal distribution of T-cell and B-cell IVL. There were four reports of IVL in cats . In two of them, the vascular lesions were limited to the brain , in one case to the brain and kidneys , and in only one case as systemic disease. No gender or breed predisposition for feline IVL was reported in those studies. No cases of feline IVL were recorded in our series. 4.1.4. Extraparenchymal Patterns Extraparenchymal (or extra-axial) lymphoma (EAL) may appear as a well-defined focal mass involving the meninges but may also diffusely invade the leptomeninges and choroid plexuses, resulting in "leptomeningeal lymphomatosis" and "lymphomatous choroiditis", respectively . Meningeal masses (MM), unlike intraparenchymal ones, are usually well-defined. They may be irregularly shaped with a whitish-gray appearance and soft texture. Sporadic malacic and hemorrhagic foci are mentioned . In this report, intracranial extraparenchymal lymphomas in cats were mainly characterized by meningeal location, usually accompanied by secondary infiltration of the neuroparenchyma. This is a frequent condition in cats, accounting for 30 to 100% of intracranial lymphomas , as a primary or multicentric type . Feline EAL was diagnosed more commonly than IPL in our series, primarily as primary types. This pathological pattern is less frequent in dogs and has been reported in a few cases . Additionally, in our series only two dogs had an occipito-temporal meningeal lymphoma and a multifocal meningeal infiltration also involving the thalamus, cerebellum, medulla oblongata, choroid plexus, and pituitary gland. In cats, most tumors described by Mandara et al. (2022) were within the cranial fossa. Interestingly, all feline MM in our study were in the forebrain, with the frontal lobe being the most common site. The median age of cats was 11 years (ranging from 4 to 17), with ESH as the main represented breed in accordance with the existing literature . Based on the immunohistochemistry results, most intracranial meningeal masses in our feline cases were B-cell lymphomas, as reported in previous studies . EAL may also develop in the choroid plexus (CP) and either grow to a recognizable mass or lead to diffuse neuroparenchymal infiltration . In both human and veterinary medicine, the latter variant, known as "lymphomatous choroiditis," is sporadically documented . In our series, four and two cases with CP involvement were observed in dogs and cats, respectively. However, neoplastic lesions within the CP were always associated with lymphoma spread to other CNS or PNS locations, both as primary and multicentric forms. An additional neuroanatomical growth pattern of extraparenchymal lymphoma is intradural lymphoma. In humans, an uncommon subtype of primary CNSL that develops from the dura mater and differs considerably from other CNSLs is called primary dural lymphoma. This tumor is classified as a mucosa-associated lymphoid tissue (MALT) lymphoma and is typically indolent . However, secondary involvement of the dura and leptomeninges is reported . In veterinary medicine, pachymeningeal lymphoma is poorly documented, and Mello et al. reported the lone occurrence of intradural lymphoma in cats. In our case series this pathological pattern was not observed. 4.1.5. Leptomeningeal Lymphomatosis When neoplastic lymphocytes show prevalent diffuse infiltration of the subarachnoid space, this pathological pattern is referred to as leptomeningeal lymphomatosis (LL), or lymphomatous meningitis, and has been reported in dogs and cats . In some reports it has been considered as a secondary evolution of an extra-nervous lymphoma , or as a primary form . Neoplastic lymphocytes are thought to directly extend from pre-existing primary or metastatic CNS tumors, from an extra-CNS mass invading the PNS, or through hematogenous dissemination into the leptomeningeal structures . However, since primary forms have been reported, the etiopathogenesis of LL remains unknown. Being frequently described alongside neoplastic infiltrates occurring in the nervous tissue, such as neurolymphomatosis or parenchymal and periventricular infiltrates , this form represents a diagnostic challenge . In the present study, two cases of canine LL (2/45; 4.4%) were detected as a multicentric form: one was found in the cerebral and cerebellar lobes, and the other involved the meninges of the entire spinal cord. Canine LL is reported to be composed of T-cell or B-cell phenotypes. Both T-cell and B-cell phenotypes were represented in our study. Recently, Mandara et al. (2022) described three cases of primary feline LL: one case with involvement limited to the brain, one to the spinal cord, and one with a pathological continuum between brain LL and neurolymphomatosis of the optic chiasm, all affecting DSH adult/elderly cats. Feline LL was also described in primary and in secondary brain lymphoma as the most frequent pathological intracranial pattern. In our study, two cases of LL were observed in cats with occasional leptomeningeal thickening. One of these was primary and limited to the brain meninges, while the second was a multicentric type affecting both the brain and spinal cord. The feline primary form described in our series was T-cell lymphoma. Notably, five out of seven primary LL described in the literature were classified as T-cell lymphoma . The two B-cell primary LL described in the literature showed rare oculo-cerebral involvement . Further studies are needed to assess whether there is an association between the phenotype and this location. Regarding LL as part of multicentric lymphoma in cats, both B-cell and T-cell phenotypes have been reported . 4.2. Intraspinal Lymphoma Lymphoma within the vertebral canal (or intraspinal lymphoma, SCL) can be categorized into three main forms with distinct biological characteristics based on anatomical location within the vertebral canal and spinal cord involvement . Extra-axial lesions may be external to the dura mater (extradural; ED) or internal to the dura mater but external to the pia and spinal parenchyma (intradural-extramedullary; ID-EM). The SCL may also be located within the spinal cord parenchyma (intramedullary; IM) . Most frequently, SCLs are reported as secondary ; however, primary forms are also described . The mechanism of primary SCL formation is not fully understood; hematopoietic tissues of extramedullary or vertebral bone have been suggested as the site of origin of spinal lymphoma . Spinal cord secondary lymphomas are thought to result from direct extension from the paravertebral regions through the vertebral foramen, or from hematogenous dissemination through the epidural venous system . Canine SCL occurs almost as frequently as in cats. The most common location is extradural , followed by intramedullary , and less commonly intradural-extramedullary location . In our study, SCL was more frequently detected in cats than in dogs, with the thoracolumbar location over-represented in both species. Cats with spinal lymphoma are often younger than those with other spinal cord tumors . In cats, the mean age at the time of diagnosis was highly variable, with 4.5 years (ranging from 8 months to 7 years) and 4 years (ranging from 1 to 11 years) for primary and secondary forms, respectively . Similarly, age at diagnosis was variable in our study, with a comparable mean age between primary (5 years; range 0.7-12 years) and secondary (6 years; range 0.7-13 years) types. No gender or breed predisposition was found in our study, as in the series reported in the literature. Clinical and pathological features of SCL may vary. It can manifest as a focal mass , multifocal masses, or extensively disseminated tumor . The lumbosacral and thoracic segments are the preferential site of onset , but lymphoma has the potential to involve any segment of the spinal cord . Furthermore, SCL is often reported in association with cranial or spinal nerves involvement, depending on the anatomical location. 4.2.1. Extradural Lymphoma Our findings on ED lymphoma are comparable to those of previous studies, where ED lymphoma was the most frequently reported pattern of SCL, described as both primary and secondary type . Both T-cell and B-cell phenotype were found, as previously reported . Most of the primary ED lymphoma in our cats and all primary types in dogs were B-cell lymphomas, whereas the B and T phenotypes were equally represented in the multicentric types. Further studies on feline SCL phenotyping and its possible association with neuroanatomical patterns are warranted. Based on the limited data available, B-cell lymphoma seems to be the most prevalent phenotype in cats. Although numerous cases have been reported in dogs, immunophenotyping was performed in only a few of them , showing that the most frequent phenotype was T-cell. 4.2.2. Intradural-Extramedullary Lymphoma In the present study, only one case of canine ID-EM lymphoma was found in a dog and three in adult cats. ID-EM has been reported in both species as an irregular mass that fills the subdural and subarachnoid spaces and tends to infiltrate contiguous segments of the spinal cord or nerve roots . In two primary intradural-extramedullary lymphomas, T-cell phenotypes were identified . In our case series, all tumors were T-cell, and in one case it was associated with intracranial meningeal involvement. 4.2.3. Intramedullary Lymphoma Intramedullary pattern is occasionally reported in dogs and cats, mainly as secondary SCL . The tumor may appear as a soft, poorly defined mass or may produce neuraxis enlargement, altering the parenchymal architecture . Hemorrhagic myelomalacia due to compression injury has been documented in cats in both intramedullary and extramedullary lymphomas . In our study, four tumors in dogs and only one tumor in a cat were classified as intramedullary SCL. Given the few cases, no differences between primary and secondary forms were identified in both species. The feline tumor was a non-B non-T lymphoma. Notably, no intramedullary B-cell lymphomas have been reported in cats . 4.3. Peripheral Nervous System Lymphoma Peripheral nerve lymphoma (or neurolymphomatosis, NL) is uncommon in dogs and rare in cats . They can involve any cranial nerve, spinal nerve roots, somatic, or autonomic nerves . The most frequently affected nerves are the trigeminal, those within the cervico-thoracic segment (C6-T2), and, more rarely, nerves of the lumbar intumescence . The neoplasms may be confined to or extend along the nerves, resulting in an intradural-extramedullary location with spinal cord compression . Multicentric NL is rarely reported in both human and animal species . Macroscopically, the affected peripheral nerve may be normal or homogeneously thickened , soft, and have yellowish discoloration , mimicking inflammatory infiltration or the less common chronic hypertrophic neuritis . Less frequently, a mass that focally deforms the nerve trunk can be observed, whereas in other cases, a large tumor mass is easily identifiable . These masses are commonly described as solid, whitish, irregularly bosselated, and non-symmetric . Complete nerve loss and replacement with a well-circumscribed white mass has also been reported . In several cases, moderate atrophy of the muscles innervated by the affected nerves was the most significant gross lesion associated with NL . In our study, the higher prevalence in dogs than in cats is in contrast with the data reported in the literature . Our results showed no breed or gender predisposition in either dogs or cats and that NL typically affected adults. The mean age of dogs and cats with NL was similar to that reported in the literature. In dogs, the prevalence of the primary type was higher than the secondary, unlike what was reported in other studies, in which all cases were secondary types. Regarding the feline species, NL was primary in most of the cases, accordingly with previous studies . The increase in the number of primary lymphoma diagnoses may be related to the development of veterinary neurology and neurosurgery referral services . In our dogs, the sciatic nerve and/or its branches was the most affected of the compartments, followed by the spinal roots, spinal nerves and spinal ganglia, and the trigeminal nerve. Similar findings have been reported in the literature . Results on the feline population showed that there was no predominance of one compartment over the others . Optic nerve involvement may be more frequent in cats . Moreover, PNS involvement with and without concurrent CNS involvement are findings similar to those reported in the literature . Data on phenotype are still fragmentary in veterinary medicine, as the only data are single case reports or small cohorts. Our results showed that there is no predominance of one phenotype over the other, but T-cells lymphomas are equally distributed among population in both dogs and cats. These results are in line with the literature . 5. Conclusions In this retrospective study we evaluated 92 cases of central and peripheral nervous system lymphoma in dogs and cats, which were studied on the basis of consistent histopathological and immunohistochemical examination. An extensive literature review was performed to collate available information on reported cases and reconcile fragmented clinical and pathological data so that our results could be compared with the available literature. In our study, no age, breed, or gender predisposition related to specific CNSL subtypes was seen in both species, even if in Labrador Retriever dogs it occurred with a slightly higher prevalence. The lone exception was the occurrence of SCL in juvenile cats, as previously reported. The overall anatomical locations of CNSL vs. PNSL, type (primary vs. secondary/multicentric), and phenotypes were similar across the species. Regarding CNSL, the forebrain was the most frequent site of lymphoma in dogs and the thoracolumbar segment was the most frequent site in cats. Primary CNSL in cats most frequently involved the forebrain meninges and, to a lesser extent, the optic nerves, especially as a B-cell phenotype. Extradural location was the most prevalent pathological pattern of SCL in both species. The B-cell phenotype predominated in primary lymphoma, whereas the B-cell and T-cell phenotypes were equally represented in the multicentric type. PNSL most frequently affected the sciatic nerves and its branches in dogs, whereas no prevalent compartment was recognized in cats. B-cell and T-cell phenotypes were equally represented in primary and multicentric PNSL in both species. Canine intravascular lymphoma mimicked a neurovascular condition rather than space-occupying or inflammatory lesions. Lymphomatosis cerebri can also occur in dogs. Clinicopathological features were variable in both species, particularly in neurolymphomatosis, due to different combinations of central and peripheral nervous system involvement. Acknowledgments We thank Lisa Baroncini for expert technical assistance in histopathology. This study follows the research topics as foreseen by the OSCAR project of the Department of Veterinary Sciences of the University of Pisa. Author Contributions Author Contributions: Conceptualization, C.C.; Methodology, N.F., F.P., C.A. and S.D.; Valida-tion, C.C.; Investigation, N.F., F.P., C.A. and S.D.; Data curation, N.F., F.P., C.A. and S.D.; Writing--original draft, N.F., F.P. and C.A.; Writing--review & editing, S.D. and C.C.; Supervision, C.C. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Ethical review and approval were waived for this study because the reported cases are descriptions of clinicopathological cases of spontaneous disease. Written informed consent was obtained from the owners for the participation of their animals in the diagnostic procedures. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Abbreviations I Primary form II Secondary/multicentric form C Cervical spinal cord cn Canine CNS Central nervous system CNSL Central nervous system lymphoma CP Choroid plexus CT Cervicothoracic spinal cord EAL Extra-axial lymphoma ED Extradural ELH European Longhair cat ESH European Shorthair cat F Female FL Forelimbs fn Feline HL Hindlimbs IC Intracranial ID-EM Intradural-extramedullary IM Intramedullary IP Intraparenchymal mass IPL Intraparenchymal lymphoma IVL Intravascular lymphoma L Lumbar spinal cord LC Lymphomatosis cerebri LL Leptomeningeal lymphomatosis M Male MM Meningeal mass NL Neurolymphomatosis NM Neutered male NSL Nervous system lymphoma PG Pituitary gland PNS Peripheral nervous system PNSL Peripheral nervous system lymphoma S Sacral spinal cord SC Intraspinal SCL Intraspinal lymphoma SF Spayed female T Thoracic spinal cord TL Thoracolumbar spinal cord Figure 1 Intracranial lymphoma: intraparenchymal pattern. (A) Case #11. Dog brain section at the level of the internal capsule. A focal extensive intraparenchymal lymphoma involves the diencephalic structures (open arrows). (B) Case #55. Feline brain section showing perivascular arrangement of intraparenchymal lymphoma with extensive infiltration of the corona radiata and diencephalic structures. Note tissue rarefaction in the central area of the neoplasia (H&E, bar = 2.5 mm). Figure 2 Intracranial lymphoma: lymphomatosis cerebri. Dog brain, case #39. (A) Dog brain section at the level of septal and basal nuclei. Bilaterally, large areas of the corona radiata and basal nuclei are grayish discolored (asterisks). The gray to white matter interface is also diffusely blurred. (B) Malignant cells diffusely infiltrate the neuroparenchyma (H&E, bar = 250 mm). (C) Neoplastic cells are immunoreactive with anti-CD3 antibody (IHC, bar = 250 mm). (D) Only a few perivascular and scattered lymphocytes within the surrounding neuroparenchyma are labelled with anti-CD20 antibody (IHC, bar = 150 mm). Figure 3 Intracranial lymphoma. (A) Intravascular lymphoma. Case #30. Dog brain section with blood vessel lumen filled with large neoplastic cells (H&E, bar = 100 mm). (B) Meningeal lymphoma. Case #58. Cat brain section with a focally extensive meningeal lymphoma (asterisk) accompanied by intraparenchymal invasion and perilesional edema causing enlargement of the right hemisphere and left shifting of the midline structures. Figure 4 Intracranial lymphoma: leptomeningeal lymphomatosis. (A) Case #40. Dog brain section in which neoplastic cells diffusely infiltrate the cerebellar leptomeninges and multifocally invade the molecular layer (H&E, bar = 100 mm). (B) Case #49. Cat brain, the surface of the cerebellum is covered by a whitish and thick layer histologically composed of neoplastic cells (asterisk). Figure 5 Feline intraspinal lymphoma. (A) Case #67. The thoracic spinal cord is focally compressed by an extradural lymphoma (open arrow). (B) Case #53. Lumbar spinal cord. Extradural accumulation of neoplastic lymphocytes with only minimal infiltration of the dura mater (H&E, bar = 1 mm). Figure 6 Peripheral nervous system lymphoma: neurolymphomatosis. (A) Case #21. Dog brain, ventral view. Both roots of the trigeminal nerve are enlarged due to infiltration of neoplastic cells (open arrows). (B) Case #89. Cat brain, ventral view. Ventral aspect of cat brain with neurolymphomatosis. All three branches of both trigeminal nerve roots (open arrows) and right optic nerve (black arrow) are enlarged due to infiltration of neoplastic cells. (C) Case #9. Canine sciatic nerve longitudinal section. Neoplastic cells extensively infiltrate the endoneurial tissue. Nerve fibers show diffuse myelin degeneration (H&E, bar = 100 mm). animals-13-00862-t001_Table 1 Table 1 Signalment, main neurological signs, and tissue sample origin of 92 cases of canine and feline central and peripheral nervous system lymphoma. Case# Species Breed Sex Age Neurological Signs Tissue Origin 1 cn Border Collie F 2 y no menace response, nystagmus, trigeminal paralysis necropsy 2 cn Mixed breed M 10 m paraparesis, back pain biopsy 3 cn German Shepherd F 8 y acute paraparesis necropsy 4 cn Cane Corso SF 5 y ataxia, depression, strabismus, left hemiparesis necropsy 5 cn Great Dane M 2.5 y monoparesis, cauda equina syndrome necropsy 6 cn Mixed breed F 6 y monoparesis biopsy 7 cn Cane Corso M 1 y paraparesis biopsy 8 cn Epagneul Breton M 2 y absent menace response, mydriasis, ataxia, head tilt necropsy 9 cn Hound F 7 y progressive weakness, ataxia, ascending paresis necropsy 10 cn Golden Retriever M 7 y multifocal intracranial syndrome necropsy 11 cn Shih-tzu M 8 y ataxia, tetraparesis, no menace response, absence of pupillary light reflex necropsy 12 cn Bulldog M 4 y right HL monoplegia biopsy 13 cn Mixed breed SF 7 y acute and progressive paraparesis biopsy 14 cn West Highland White Terrier M 4 y forebrain syndrome, blindness necropsy 15 cn Labrador Retriever NM 12 y paraplegia necropsy 16 cn Labrador Retriever M 6 y tetraparesis necropsy 17 cn Yorkshire Terrier M 7 y paraparesis necropsy 18 cn Border Collie SF 13 y right head tilt, brainstem syndrome necropsy 19 cn Beagle M 7 y acute paraparesis necropsy 20 cn Mixed breed M 10 y cervical pain, tetraparesis necropsy 21 cn Staffordshire Terrier F 6.5 y | menace response, masticatory muscles atrophy, | facial sensitivity necropsy 22 cn Labrador Retriever F 3 y left HL monoplegia, right HL monoparesis necropsy 23 cn Mixed breed M 4.5 y paraparesis biopsy 24 cn Rottweiler M 2 y depression, ataxia, no menace response, anisocoria, | facial sensitivity necropsy 25 cn Labrador Retriever M 7 y forebrain syndrome necropsy 26 cn Bergamasco Shepherd M 7 y paraparesis, severe depression necropsy 27 cn Boxer F 3.5 y forebrain syndrome necropsy 28 cn English Cocker Spaniel M 11 y forebrain syndrome necropsy 29 cn Boxer F 4 y intracranial multifocal syndrome, seizures necropsy 30 cn Pointer M 13 y paraparesis, depression necropsy 31 cn German Shepherd F 9 y tetraparesis, depression necropsy 32 cn Mixed breed SF 12 y right hemiparesis necropsy 33 cn Dachshund F 2.5 y depression, seizures necropsy 34 cn Boxer F 10.5 y seizures necropsy 35 cn Mixed breed F 4 y tetraplegia necropsy 36 cn Mixed breed M 14 y left HL monoparesis necropsy 37 cn Mixed breed M 9 y tetraparesis necropsy 38 cn German Shepherd F 3 y paraparesis necropsy 39 cn Hound F 2 y severe depression, tetraparesis necropsy 40 cn Boxer F 7 y neck pain, intracranial syndrome necropsy 41 cn Mixed breed M 14 y central vestibular syndrome necropsy 42 cn Amstaff M 3 y right HL progressive lameness biopsy 43 cn Cane Corso F 7 y monoplegia biopsy 44 cn Rottweiler F 4.5 y right HL monoparesis biopsy 45 cn Labrador Retriever M 10 y tetraparesis, paraplegia biopsy 46 fn ESH F 9 y bilateral blindness, depression, seizures, necropsy 47 fn ESH F 5 y ataxia, left HL monoparesis, strangury biopsy 48 fn Persian M 11 y seizures, ataxia, blindness necropsy 49 fn ESH M 6 y progressive paraparesis, ataxia necropsy 50 fn ESH F 14 y ataxia, depression necropsy 51 fn ESH M 9 y ataxia, depression, vertical nystagmus biopsy 52 fn ESH NM 14 y depression, compulsive gait necropsy 53 fn ESH M 11 y paraplegia necropsy 54 fn ESH M 8 y forebrain syndrome biopsy 55 fn ESH NM 17 y seizures, depression, tetraparesis, bilateral mydriasis necropsy 56 fn ESH M 8 y left FL monoplegia and muscle atrophy necropsy 57 fn ESH SF 5 y paraplegia biopsy 58 fn ESH F 12 y forebrain syndrome necropsy 59 fn ESH M 3 y paraplegia necropsy 60 fn ESH M 1 y back pain, paraparesis biopsy 61 fn ESH F 10 y prosencephalic syndrome necropsy 62 fn ESH NM 11 y depression, right drifting, compulsive gait biopsy 63 fn ESH NM 12 y compulsive gait, left circling necropsy 64 fn ESH NM 4 y seizures necropsy 65 fn ESH SF 12 y progressive tetraparesis necropsy 66 fn ESH M 11 y left blindness, forebrain syndrome necropsy 67 fn ESH M 4 y paraparesis necropsy 68 fn ESH SF 5 y progressive paraparesis biopsy 69 fn ESH SF 15 y blindness, forebrain syndrome necropsy 70 fn ESH SF 8 y ataxia, behavioral changes, mydriasis, left pleurothotonus necropsy 71 fn ESH NM 9 y brainstem syndrome necropsy 72 fn ESH SF 4 y paraplegia biopsy 73 fn ESH NM 1 y paraplegia, loss of deep pain sensation biopsy 74 fn Ragdoll F 3 m seizures necropsy 75 fn ESH SF 3 y paraplegia necropsy 76 fn ESH M 10 y paraplegia, back pain necropsy 77 fn Maine Coon F 13 y depression, paraparesis necropsy 78 fn ESH SF 8 m paraparesis biopsy 79 fn ESH M 8 m paraplegia, loss of deep pain sensation necropsy 80 fn Norwegian Forest cat SF 11 y depression, weakness, | left menace response and left pupillary light reflex necropsy 81 fn ESH F 12.5 y left circling, anisocoria, left miosis, right FL monoparesis necropsy 82 fn Carthusian M 6 y progressive paraparesis necropsy 83 fn ESH SF 10 y paraparesis necropsy 84 fn ESH F 2 y acute paraplegia necropsy 85 fn ESH SF 11 y tetraparesis necropsy 86 fn Siamese SF 7 y paraparesis, hyperesthesia, | pain sensation, ataxia, urinary loss necropsy 87 fn ESH F 7 y severe paraparesis biopsy 88 fn ESH M 14 y right hemiparesis necropsy 89 fn ESH SF 7 y acute tetraplegia, dysphagia, right Horner syndrome necropsy 90 fn ESH M 14 y progressive tetraparesis biopsy 91 fn ELH SF 12 y right HL monoplegia biopsy 92 fn ESH SF 11 y lameness and monoparesis biopsy cn = canine; fn = feline; ESH = European Shorthair cat; ELH = European Longhair cat; M = male; NM = neutered male; F = female; SF = spayed female; y = years; m = months; FL = forelimbs; HL = hindlimbs; | = reduced. animals-13-00862-t002_Table 2 Table 2 Type, anatomical site, location, distribution, pathological pattern, nuclear size, grading, and phenotype of nervous system lymphoma in 92 canine and feline cases. Ndeg Species Type Anatomical Site Location and Distribution Pathological Pattern Nuclear Size Grading Phenotype 1 cn II IC occipital lobe IP large medium B 2 cn I SC T10-T13 ED intermed. low B 3 cn II SC L3-L5 ED large high B 4 cn II IC occipito-temporal lobe IP, MM large high T 5 cn II SC, PNS cauda equina, sciatic nerve IM, NL small low B 6 cn I PNS L6 nerve root NL large high B 7 cn I SC T9 ED large high B 8 cn II IC occipital lobe IP large high non-B, non-T 9 cn II SC, PNS LS, sciatic nerves IM, NL large high T 10 cn I IC, PNS parieto-occipital lobes, V nerve root IP, NL large high B 11 cn II IC basal nuclei IP large high T 12 cn II PNS ischiatic nerve NL large high B 13 cn II PNS L1 nerve root NL large high B 14 cn II IC occipital lobe IP large high B 15 cn II SC L ED large high B 16 cn II SC C3-C6 ED large medium B 17 cn II SC T11-T13 ED small low T 18 cn II IC thalamus, cerebellum, m. obl., CP, PG IP, MM large high B 19 cn I SC T6-T7 IM large high non-B, non-T 20 cn I SC C3-C4 IM intermed. low B 21 cn I IC, PNS trigeminal nerves, CP NL intermed. low B 22 cn I SC L4-L7 ED large high B 23 cn II SC T12-L1 ED large high B 24 cn I IC thalamus IP large high B 25 cn I IC multifocal IVL large ND B 26 cn I IC multifocal IVL large ND non-B, non-T 27 cn I IC multifocal IVL large ND T 28 cn I IC multifocal, CP IVL large ND non-B, non-T 29 cn I IC multifocal IVL large ND B 30 cn I IC multifocal, CP IVL large ND B 31 cn I IC multifocal IVL large ND T 32 cn II IC multifocal IVL large ND non-B, non-T 33 cn I IC multifocal IVL large ND T 34 cn I IC multifocal IVL large ND non-B, non-T 35 cn II SC C, CT, TL, LS ID-EM, LL small medium B 36 cn I PNS L femoral nerve NL large high T 37 cn II PNS multiple spinal nerves NL intermed. low T 38 cn II SC T ED small medium T 39 cn I IC diffuse LC intermed. medium T 40 cn II IC frontal, temporal, cerebellar lobes LL large high T 41 cn II IC ponto-cerebellar angle IP large high B 42 cn I PNS L5 nerve root NL large low B 43 cn I PNS sciatic nerve NL large low T 44 cn I PNS sciatic nerve NL large medium T 45 cn I PNS sciatic nerves NL small low T 46 fn I IC optic nerves, diencephalon IP intermed. medium B 47 fn I SC L4-L5 ED intermed. low B 48 fn II IC parietal lobe IP intermed. medium T 49 fn II IC, SC cerebellar, T LL, ED large medium B 50 fn I IC frontal lobe IP, MM large high non-B, non-T 51 fn I IC frontal lobe IP, MM large high B 52 fn II IC frontal lobe, CP IP, MM large high B 53 fn II SC LS ED small medium T 54 fn I IC parietal lobe IP, MM large high B 55 fn I IC diencephalon, thalamus IP, MM small low T 56 fn II PNS brachial plexus NL large medium T 57 fn I SC T12-L1 ED small low B 58 fn I IC frontal lobe, diencephalon IP, MM large high T 59 fn I SC L5-L6 ED large medium B 60 fn II SC L1 ED large high B 61 fn II IC frontal lobe MM large medium non-B, non-T 62 fn I IC frontal lobe IP intermed. medium T 63 fn I IC frontal lobe IP, MM large high B 64 fn I IC frontal lobe IP, MM large high B 65 fn I SC CT IM large high non-B, non-T 66 fn II IC diencephalon IP, MM intermed. high B 67 fn II SC T8 ED large high B 68 fn I SC L3 ED large medium B 69 fn II IC diencephalon IP, MM large high B 70 fn II IC medulla oblongata IP intermed. low B 71 fn II IC medulla oblongata IP large low T 72 fn I SC L3-L4 ED small medium B 73 fn II SC T11 ED small medium T 74 fn I PNS cervical spinal nerves NL large low B 75 fn I SC TL ED small low T 76 fn II SC TL ID-EM intermed. low T 77 fn II IC, SC cerebral cortex, m. obl., T ID-EM, MM small medium T 78 fn I SC T5-T7 ED intermed. medium B 79 fn II IC, SC TL, CP MM, ED small low B 80 fn I IC olfactory lobe IP, MM large high B 81 fn I IC parietal lobe IP, MM intermed. medium T 82 fn II IC, PNS C and TL nerve roots NL small low B 83 fn II SC TL ED small low T 84 fn II SC TL ED small low B 85 fn II SC CT ED intermed. medium T 86 fn I SC LS ED intermed. low non-B, non-T 87 fn I SC T11-T12 ID-EM large medium T 88 fn I IC forebrain, midbrain LL large high T 89 fn I IC, PNS II, V cranial, brachial, sciatic nerves NL intermed. low B 90 fn I PNS C7 nerve root NL small low T 91 fn I PNS sciatic nerve NL small medium T 92 fn I PNS sciatic nerve NL large medium B cn = canine; fn = feline; I = primary form; II = secondary/multicentric form; IC = intracranial; SC = intraspinal; PNS = peripheral nervous system; C = cervical; CT = cervicothoracic; T = thoracic; L = lumbar; TL = thoracolumbar; S = sacral spinal cord; CP = choroid plexus; PG = pituitary gland; IP = intraparenchymal mass; MM = meningeal mass; LL = leptomeningeal lymphomatosis; IVL = intravascular lymphoma; LC = lymphomatosis cerebri; ED = extradural; ID-EM = intradural-extramedullary; IM = intramedullary; NL = neurolymphomatosis, ND = not determined. 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PMC10000238 | Evaluating the association between milk-containing diets and the microbiomes of young Asian elephants could assist establishing optimal breast milk supplementation to improve offspring survival rates. The microbiomes of young Asian elephants on different milk-containing diets (elephant milk only, elephant milk-plant mixed feed, and goat milk-plant mixed feed) were investigated using high-throughput sequencing of 16S rRNA genes and phylogenetic analysis. Microbial diversity was lower in the elephant milk-only diet group, with a high abundance of Proteobacteria compared to the mixed-feed diet groups. Firmicutes and Bacteroidetes were dominant in all groups. Spirochaetae, Lachnospiraceae, and Rikenellaceae were abundant in the elephant milk-plant mixed-feed diet group, and Prevotellaceae was abundant in the goat milk-plant mixed-feed diet group. Membrane transport and cell motility metabolic pathways were significantly enriched in the elephant milk-plant mixed-feed diet group, whereas amino acid metabolism and signal transduction pathways were significantly enriched in the goat milk-plant mixed-feed diet group. The intestinal microbial community composition and associated functions varied significantly between diets. The results suggest that goat milk is not suitable for young elephants. Furthermore, we provide new research methods and directions regarding milk source evaluation to improve elephant survival, wellbeing, and conservation. Asian elephant intestinal microbiota diet elephant milk goat milk National Natural Science Foundation of China32260015 Scientific Research Foundation of Education Department of Yunnan Province2023J0202 This research was funded by the National Natural Science Foundation of China, grant number 32260015 and Scientific Research Foundation of Education Department of Yunnan Province, grant number 2023J0202. pmc1. Introduction The Asian elephant (Elephas maximus) is a large phytophagous mammal that is mainly found in the Xishuangbanna region of Yunnan Province, China, south of 24.6deg north latitude, and in parts of south and southeast Asia . The Asian elephant is a Class I protected wildlife species in China and is listed as endangered by the International Union for Conservation of Nature Red List of Threatened SpeciesTM . Furthermore, these elephants are in Appendix I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora . There are only approximately 300 Asian elephants left in China . Although the Asian elephant population has rebounded after years of effort, its survival rate still requires improvement. Approximately 25.6% of elephant calves in Myanmar reportedly die before they reach 5 years of age, with a quarter of these deaths attributed to insufficient maternal milk or the inability of the calves to receive the milk properly . Similarly, in wild African elephant populations, an average of 19% of young elephants die before 5 years of age, with a proportion of these deaths attributed to maternal difficulties regarding meeting nursing needs . During droughts, maternal elephants struggle to maintain milk production, when the metabolic demands of young male elephants are greater, making it difficult for maternal elephants to meet their needs. Thus, young male elephants are more likely to die . A major reason for the high mortality rate of elephant calves in zoos, especially in Asia, is the refusal of mothers to nurse their young, resulting in the need for manual intervention to feed the young . Inadequate maternal milk in Asian elephants results in the poor survival rate of young elephants, and currently, staff at the Xishuangbanna Asian Elephant Sanctuary are using goat milk to supplement the feeding of rescued infants and young elephants. The large number of microbial communities present in the gastrointestinal tract of animals constitute the microbiota, which contribute to host nutrient acquisition and immune regulation and assist in maintaining host homeostasis in response to environmental changes . Diet, especially early nutrition, influences the composition and metabolic activity of the gut microbial community and is a key factor in the growth and healthy development of newborn elephants . Breastfeeding is considered an influential driver of the gut microbiota composition during infancy, potentially affecting the function thereof . The gut microbiota early in life is associated with physiological development, and early gut microbiota is involved in a range of host biological processes, particularly immunity, cognitive neurodevelopment, metabolism, and infant health . Early foods can promote the survival rate of infant and young elephants; therefore, it is vital to study the effects of different foods, especially different kinds of milk on the gut microbiota of infant and young elephants. In this study, the gut microbiota composition and function of young elephants fed an elephant milk-only diet, elephant milk-plant mixed-feed diet, and goat milk-plant mixed-feed diet were analyzed using 16S rRNA gene high-throughput sequencing technology. Although there have been studies regarding the use of non-breast milk dairy products for feeding endangered wildlife (e.g., Siberian tigers ), only few studies on the gut microbiota of Asian elephants on diets containing goat milk exist. To the best of our knowledge, this study is the first to describe the composition and function of the gut microbiota of young elephants fed a goat milk diet. 2. Materials and Methods 2.1. Fecal Sample Collection In March 2019, we collected fresh feces from eight young Asian elephants with different milk-containing diets at Wild Elephant Valley in Xishuangbanna: three in the elephant milk diet-only group (BF1, BF2, and BF2; they are healthy, aged about 6 months, and can freely shuttle below the abdomen of adult female elephants); three in the elephant milk-plant mixed feeding group (BPM1, BPM2, and BPM3; they are healthy, more than one year old, and tall to the base of the forelegs of adult female elephants); and two in the goat milk-plant mixed feeding group (GPM1 and GPM2; they are healthy, more than three year old, and height slightly higher than the previous group). The detailed sampling method was as follows : young elephants were accompanied by the breeder until defecation, samples were collected immediately from the center of fresh feces with sterile tweezers, placed in sterile centrifuge tubes, and stored in liquid nitrogen. Samples were transported in liquid nitrogen, and then stored at -80 degC until DNA extraction. 2.2. Genomic DNA Extraction, Gene Amplification and High-Throughput Sequencing Microbial genetic DNA was extracted from eight fecal samples using the EZNA(r) Soil DNA Kit (Omega, GA, USA) following the steps in the kit instructions. DNA quality and quantity were assessed using a 1% agarose gel and a NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). The hypervariable region V3-V4 of the bacterial 16S rRNA gene was amplified with the primer pair 338F (5'-ACTCCTACGGGAGGCAGCAG-3') and 806R (5'-GGACTACHVGGGTWTCTAAT-3') using an ABI GeneAmp 9700 PCR thermal cycler (Appliedbiosystems, Foster City, CA, USA). The PCR mix consisted of 4 mL of 5x TransStart FastPfu buffer, 2 mL of 2.5 mM dNTP, 0.8 mL each of 5 mM forward and reverse primers, 0.4 mL of TransStart FastPfu DNA polymerase, 10 ng of template DNA and ddH2O up to 20 mL. PCR amplification was performed in triplicate under the following conditions: 95 degC for 3 min, followed by 30 cycles of 95 degC for 30 s, 55 degC for 30 s, and 72 degC for 45 s, and a final extension at 72 degC for 10 min. Purified amplicons were pooled in equimolar aliquots and then sequenced on the Illumina MiSeq platform (Illumina, San Diego, CA, USA) to obtain paired-end reads . 2.3. Sequencing Data Processing Raw 16S rRNA gene sequencing reads were demultiplexed and quality-filtered using fastp version 0.20.0 and then merged using FLASH version 1.2.7 . Stringent criteria were established for quality. Three hundred-base pair reads were truncated at any site that received an average quality score <20 over a 50 bp sliding window. Truncated reads shorter than 50 bp and reads with ambiguous characters were discarded. Sequences required an overlap larger than 10 bp for assembly, and the maximum mismatch ratio of the overlap region was 0.2. Reads that could not be assembled were discarded. Samples were distinguished by barcodes and primers, and the sequence direction was adjusted accordingly. Exact barcode matching was required, and a mismatch of two nucleotides in primer matching was allowed. Operational taxonomic units (OTUs) with a 97% similarity cutoff were clustered using UPARSE version 7.1 ; chimeric sequences were identified and removed. Taxon assignments for each representative OTU sequence were determined using RDP Classifier version 2.2 with the 16S rRNA gene database (Silva v138) with a confidence threshold of 0.7. 2.4. Data Analysis and Statistical Methods To investigate the similarity and difference relationship of microbial community structure among different milk-containing diet groups, sample-level clustering analysis was performed using UPGMA method based on the average Bray_curtis distance matrix among groups. Alpha diversity indices including Chao1 index, Shannon index, and Pielou index were calculated using software mothur (version 1.30.2, accessed on 23 April 2019), and difference tests between multiple groups were performed using Welch's t-test. The Kruskal-Wallis H test was applied to detect species that exhibited differences in abundance in the microbial communities between groups. In addition, functional prediction results were obtained using PICRUSt2, and the difference significance was detected using the Kruskal-Wallis H test. 3. Results 3.1. Unweighted Pair Group Method with Arithmetic Mean Hierarchical Clustering Analysis At the family and genus levels, the samples were analyzed using hierarchical clustering based on the unweighted pair group method with arithmetic mean (UPGMA) cluster analysis method , which indicated that the samples were clearly clustered into two groups: the elephant milk diet group (BF1, BF2, and BF2) and the milk-plant mixed-feed diet group (remaining samples). The milk-plant mixed-feed diet group was clearly further divided into two groups according to the type of supplemented milk: the elephant milk-plant mixed-feed diet group (BPM1, BPM2, and BPM3) and the goat milk-plant mixed-feed diet group (GPM1 and GPM2). These results exhibited that the gut microbial community composition of young elephants in the elephant milk-only diet group and that of young elephants in the milk-plant mixed-feed diet groups differed clearly. Moreover, the gut microbial community composition of young elephants in the elephant milk-only diet group and that of young elephants in the goat milk-plant mixed-feed diet group also differed significantly. 3.2. Alpha Diversity Analysis An a-diversity test was performed to evaluate the differences in the gut microbial community between the three groups at the family level . Consequently, the richness index (Chao1) and diversity index (Shannon) were significantly different between the three groups . The richness and diversity indices of the milk-plant mixed-feed diet groups were significantly higher than those of the elephant milk-only diet group (p < 0.05), which was consistent with the richness of dietary diversity in the milk-plant mixed-feed diet groups. In addition, the Shannon and Pielou indices were significantly higher in the elephant milk-plant mixed-feed diet group than in the goat milk-plant mixed-feed diet group . These findings suggested that supplementation with elephant milk in young elephants resulted in a more diverse and homogeneous gut bacterial community than supplementation with goat milk, and supplementation with goat milk may lead to a highly dominant bacterial taxon in the gut environment of young elephants. 3.3. Community Composition Firmicutes and Bacteroidetes represented the dominant phyla in young elephant guts, which was consistent with the dominant phyla in the gut microbiota of adult Asian elephants . The young elephant intestinal microbiota in the elephant milk-only diet group (BF1, BF2, and BF3) contained a high abundance of Proteobacteria, averaging around approximately 17.3% . The elephant milk-plant mixed-feed diet group (BPM1, BPM2, and BPM3) had a higher abundance of Spirochaetae (approximately 8.8%), Fibrobacteria (approximately 3.8%), and Verrucomicrobia (approximately 3.6%) compared to the elephant milk-only diet group . The BPM1 group had a relatively higher intake of elephant milk and, correspondingly, higher abundance of Proteobacteria, while BPM2 and BPM3, which had lower intakes of elephant milk, had an extremely low abundance of Proteobacteria, indicating that elephant milk is closely related to Proteobacteria levels. The goat milk-plant mixed-feed diet group (GPM1 and GPM2) contained nearly no Proteobacteria, Spirochaetae, and Fibrobacteria , and the considerably low abundance of Proteobacteria indicated that elephant milk is closely related to the abundance of this bacterium. In addition, Synergistetes were abundant in the intestinal microbiota of young elephants in the goat milk-plant mixed-feed diet group compared to the other groups . At the family level, the intestinal bacteria of young elephants in the elephant milk-only diet group consisted mainly of Bacteroidaceae, Enterobacteriaceae, Ruminococcaceae, and Lachnospiraceae, accounting for >75% of intestinal bacteria . The intestinal bacteria of young elephants in the elephant milk-plant mixed-feed diet group consisted mainly of Lachnospiraceae, Ruminococcaceae, Rikenellaceae, Spirochaetaceae, and Prevotellaceae, accounting for >70% of intestinal bacteria . BPM1, who consumed a large amount of elephant milk, had an abundance of Enterobacteriaceae, suggesting that Enterobacteriaceae levels are closely related to the elephant milk consumed by young elephants. The intestinal bacteria of young elephants in the goat milk-plant mixed-feed diet group consisted mainly of Ruminococcaceae, Lachnospiraceae, Prevotellaceae, and Synergistaceae, accounting for approximately 60% of intestinal bacteria . 3.4. Differential Microbiota Analysis At the family level, differential microbiota analysis of young elephants revealed that Rikenellaceae, Spirochaetaceae, Fibrobacteraceae, and Bacteroidales_UCG-001 were significantly enriched in the elephant milk-plant mixed-feed diet group (p < 0.05). These bacterial taxa belong to the lignocellulose-degrading bacterial phyla commonly encountered in the gastrointestinal tracts of animals, such as Bacteroidetes, Spirochaetes, and Fibrobacteres, suggesting that elephant milk enriches lignocellulose-digesting bacterial groups in the intestinal tract of young elephants, facilitating the transition from an elephant milk diet to a plant-based diet. Prevotellaceae, Synergistaceae, and Christensenellaceae were significantly enriched in the goat milk-plant mixed-feed diet group (p < 0.05). This indicated that there was a significant difference in the effect of elephant and goat milk supplementation in the diet on the intestinal microbiota of young elephants. 3.5. Function Predictive Analysis Predictive analysis of the intestinal microbiota function in young elephants revealed differences in microbial community functions between different milk-containing diet groups . Carbohydrate and cofactor metabolism, vitamins, and glycan biosynthesis and metabolism were significantly more enriched in the elephant milk-only diet group compared to the mixed-feed diet group (p = 0.044). These function enrichments were beneficial to infant elephant growth and development. The enrichment of nucleotide metabolism (p = 0.044) and biosynthesis of other secondary metabolites (p = 0.044) were significantly higher in the goat milk-plant mixed-feed diet group compared to that of the elephant milk-only diet group, indicating that secondary metabolic pathways occurred during food digestion in the goat milk-plant mixed-feed diet group. The other amino acid metabolic (p = 0.030), transformation (p = 0.046), transcriptional (p = 0.020), replication and repair (p = 0.030), endocrine system (p = 0.044), and cell growth and death metabolic (p = 0.030) pathways were also significantly more enriched in the elephant milk-plant mixed-feed diet group than in the elephant milk-only diet group. The significant enrichment of these functions reflected strong metabolism and good growth and development of the young elephants in this group, indicating that the elephant milk-plant mixed-feed diet promoted the transition of young elephants from an elephant milk-based diet to a plant-based diet. In the elephant milk-plant mixed-feed diet group, enrichment of the membrane transport pathway (p = 0.044) and cell motility pathway (p = 0.044) was significantly higher in the elephant milk-plant mixed-feed diet group than in the goat milk-plant mixed-feed diet group. Meanwhile, the energy metabolic (p = 0.044), amino acid metabolic (p = 0.044), and signal transduction (p = 0.025) pathways were significantly more enriched in the goat milk-plant mixed-feed diet group than in the elephant milk-plant mixed-feed diet group. These results suggested that supplementation of the host's diet with milk from different sources led to changes in the functional structure of the gut microbiota in Asian elephants. 3.6. Composition Comparison of Different Kinds of Milk There were significant differences in the composition and function of the gut microbiota between the elephant milk diet groups and the goat milk diet group of young elephants . Moreover, there was a close correlation between the host's diet and their gut microbiota , where diet may have represented the main reason for these differences. Previous studies have shown significant differences in the nutrient composition of Asian elephant milk compared to goat milk . In the Asian elephant milk, the total solids (17.56-19.60%), protein (3.30-5.23%), and milk fat (7.70-8.30%) content were significantly higher than those in the goat milk (11.53-13.00%, 3.17-3.75%, and 3.95-4.25% for total solids, protein, and fat contents, respectively), while the water content (81.90-82.44%) was significantly lower than that of the goat milk (88.00%) (Table 1). The differences in the gut microbiota composition and function between the mixed-feed diet groups in this study may be mainly due to the differences in the nutrient composition and content between elephant milk and goat milk. Comparisons of the nutrient composition and content of different kinds of milk and Asian elephant milk have been conducted in previous studies . The nutritional composition and content of yak milk was similar to that of Asian elephant milk (Table 1). Water, total solids, protein, milk fat, ash, and lactose accounted for 83.74%, 16.60-18.52%, 4.68-5.41%, 6.72-8.18%, 0.72-1.19%, and 4.40-5.10% of yak milk, respectively (Table 1). Although there has been no study on the intestinal microbiota of Asian elephants supplemented with yak milk, the similarity between the composition and content of yak milk and Asian elephant milk suggests that yak milk may represent a viable choice of milk compared to goat milk for the supplementation of rescued young Asian elephants. 4. Discussion Asian elephants are endangered wild animals, and there are few milk-drinking young elephants. Although the number of samples in each group in this study is insufficient, this is all the samples that could be collected in Xishuangbanna region at that time. Here, the diversity of gut microbial communities of young elephants differed significantly between different milk-based diet groups, reflecting the various effects that these diets may have on the growth and development of young elephants. The richness (Chao 1 index) and diversity (Shannon index) of human intestinal microbiota are crucial indicators of health . Claesson et al. reported that preterm infants with necrotizing colitis have a significantly lower diversity of fecal microbiota compared to those without the disease, and young children with lower gut microbiota diversity are at higher risk of developing allergic diseases later in life. Thus, the greater the gut microbiota richness and diversity, the more likely it is that the nutritional status and health of the host will be good. In this study, the elephant milk-plant mixed-feed diet group had higher intestinal microbiota diversity compared to the goat milk-plant mixed-feed diet group; therefore, although it is feasible to feed goat milk to young elephants, these results suggest that more suitable milk sources should be identified to serve as appropriate elephant milk supplementation for Asian elephants. Firmicutes and Bacteroidetes were the dominant phyla in all three groups, which is consistent with the results of Ilmberger et al. , and are also the dominant phyla in the adult Asian elephant gut microbiota . Intestinal Firmicutes have many genes encoding fermentable dietary fiber proteins, which can also interact with the intestinal mucosa, contributing to the stability of the host's internal environment . Bacteroidetes are the main drivers of plant biomass degradation in Asian elephants . These two bacterial taxa are indispensable for Asian elephants, as they assist plant digestion for energy acquisition. In the goat milk-plant mixed-feed diet group, the dominant phyla in the gut remained Firmicutes and Bacteroidetes, indicating that the use of goat milk to feed young Asian elephants could maintain the stability of the dominant phyla in the intestinal microbiota, allowing digestion and energy acquisition from food. The abundance of Spirochaetae in the intestinal microbiota of young Asian elephants was higher in the elephant milk-plant mixed-feed diet group compared with the goat milk-plant mixed-feed diet group. Spirochaetae are associated with the cell motility pathway, which is required by intestinal microbiota to actively contact their substrates and facilitate the biochemical reactions of the substrates . This suggests that goat milk is not the most suitable supplement for elephant milk. In addition, Lachnospiraceae were more abundant in young Asian elephants in the elephant milk-plant mixed-feed diet group compared to in the goat milk-plant mixed-feed diet group, and are closely associated with host mucosal integrity, bile acid metabolism, and polysaccharide catabolism . The low Lachnospiraceae abundance in the goat milk-plant mixed-feed diet group further suggested that goat milk may not be the best choice for feeding young Asian elephants. The abundance of Prevotellaceae and Rikenellaceae was higher in the mixed-feed diet groups than in the elephant milk-only diet group. A low abundance of Rikenellaceae and a high abundance of Prevotellaceae have been associated with obesity . Therefore, the lower abundance of Rikenellaceae and higher abundance of Prevotellaceae in the goat milk-plant mixed-feed diet group compared to the elephant milk-plant mixed-feed diet group suggest that goat milk-plant mixed feeding may cause obesity in Asian elephants. In turn, this could lead to a potential risk of obesity-related diseases in Asian elephants. Synergistaceae encode multiple pathways that may be associated with the metabolism of diet-generated compounds , and these are predicted to be key factors in dietary detoxification in herbivores. In this study, Synergistaceae were significantly enriched in the goat milk-plant mixed-feed diet group, which was consistent with the significant enrichment of biosynthesis of other secondary metabolites in this group. This was likely due to the excess of secondary metabolism occurring during food digestion in this group. Meanwhile, the reason behind excess secondary metabolism, caused by the supplementation of goat milk or the presence of specific components in the foraged plants, requires further elucidation. Recent studies on the relationship between breast milk and the gut microbiota have revealed a correlation between milk composition and gut microbiota in infants , and that milk composition varies by mammalian species . The composition and content of Asian elephant and goat milk differ significantly. Asian elephant milk is richer in nutrients than goat milk, which may have been the main reason for the difference in the composition and function of the gut microbiota between the elephant milk-plant mixed-feed diet group and the goat milk-plant mixed-feed diet group. Nutrient composition analysis and the content of yak milk indicates that it is similar to Asian elephant milk. Furthermore, through the study of yak milk on retinoic acid-induced osteoporosis in mice, it was found that yak milk could improve bone quality and microstructure to promote bone health . The study of Zhang Wei et al. showed that yak milk could improve endurance capacity and relieve fatigue . It is reported that yak dairy products seem to be particularly rich in functional and bioactive ingredients, which may play a role in maintaining the health of nomadic peoples . Nutritional composition analysis of yak milk and its advantages in other animals suggested that yak milk may be an ideal source of supplemental milk for Asian elephants, compared to goat milk. 5. Conclusions By studying the gut microbiome of Asian elephants on different milk-containing diets, it revealed the fact that the diet supplemented with goat milk diet seems not to be the most indicated to young elephants, and the composition and function of the gut microbiota of young elephants on a supplemented goat milk diet were also revealed for the first time, which were compared with those on an elephant milk diet only and an elephant milk-plant mixed-feed diet. This study presents a breakthrough in a new research area, the gut microbiome, regarding the serious problem of a low survival rate of infant and young elephants due to insufficient breast milk. Furthermore, we demonstrate the importance of finding a more suitable supplemental or alternative source of breast milk for Asian elephants. We believe that, in the future, with the help of wildlife gut microbiome analysis, the best supplemental or alternative sources of milk can be identified for other endangered wildlife infants and young to enhance the wellbeing of wildlife and relieve the threat to survival caused by insufficient breast milk. Acknowledgments Thanks to Mingwei Bao, Qingzhong Shen, and Chaoyong Xiong for their help in the sampling process. Author Contributions Conceptualization, C.Z.; methodology, C.Z.; software, C.Z. and J.C.; formal analysis, C.Z. and J.C.; resources, Q.W. and B.X.; writing--original draft preparation, C.Z. and J.C.; writing--review and editing, C.Z. and Z.H.; visualization, C.Z. and J.C.; supervision, Z.H.; project administration, C.Z. and Z.H.; funding acquisition, C.Z. and Z.H. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement The data supporting the results of this study can be found in the manuscript. Raw sequence data obtained in this Raw sequence data obtained in this study have been deposited in the Genome Sequence Archive of the BIG Data Center of the Chinese Academy of Sciences (GSA: CRA009476) and are publicly accessible at (accessed on 1 March 2023). Conflicts of Interest The authors declare no competing financial interests related to this article. Figure 1 (a) Hierarchical clustering tree of species at the family level obtained from samples based on the unweighted pair group method with arithmetic mean (UPGMA) clustering analysis method; (b) species-level hierarchical clustering trees at the genus level obtained from samples based on the UPGMA cluster analysis method. BF1, BF2, and BF2 refer to the elephant milk-only diet group, BPM1, BPM2, and BPM3 refer to the elephant milk-plant mixed-feed diet group, and GPM1 and GPM2 refer to the goat milk-plant mixed-feed diet group. Figure 2 Analysis of the a-diversity of microbial communities. (a) Chao 1 index; (b) Shannon index; and (c) Pielou index. BF refers to the elephant milk-only diet group, BPM refers to the elephant milk-plant mixed-feed diet group, and GPM refers to the goat milk-plant mixed-feed diet group. * refers to p < 0.05, ** refers to p < 0.01. Figure 3 Gut microbial community composition of young elephants at the phylum level. Figure 4 Differential gut microbiota analysis of young elephants. *: Significant difference. Figure 5 Predictive analysis of the gut microbial function in young elephants. * Metabolic pathways that were significantly different between groups (p < 0.05). animals-13-00916-t001_Table 1 Table 1 Comparison of the nutrient composition and content of various kinds of milk. Nutritional Composition Asian Elephant Milk Goat Milk Yak Milk Camel Milk Sheep Milk Moisture 81.90-82.44% 88.00% 83.74% 85.0-90.0% 88% Total solids 17.56-19.60% 11.53-13.00% 16.60-18.52% 9.95-16.31% 9.60-9.95% Protein 3.30-5.23% 3.17-3.75% 4.68-5.41% 3.00-4.19% 3.18-3.29% Milk fat 7.70-8.30% 3.95-4.25% 6.72-8.18% 4.43-6.26% 6.79-7.20% Ash 0.40-0.87% 0.79% 0.72-1.19% 0.68-0.71% 0.93-0.96% Lactose 3.00-4.90% 4.20-4.82% 4.40-5.10% 4.25-5.43% 5.49-5.70% Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000239 | This work aimed to determine the physicochemical and biochemical properties of trypsin from beluga Huso huso and sevruga Acipenser stellatus, two highly valuable sturgeon species. According to the results obtained from the methods of casein-zymogram and inhibitory activity staining, the molecular weight of trypsin for sevruga and beluga was 27.5 and 29.5 kDa, respectively. Optimum pH and temperature values for both trypsins were recorded at 8.5 and 55 degC by BAPNA (a specific substrate), respectively. The stability of both trypsins was well-preserved at pH values from 6.0 to 11.0 and temperatures up to 50 degC. TLCK and SBTI, two specific trypsin inhibitors, showed a significant inhibitory effect on the enzymatic activity of both trypsins (p < 0.05). The enzyme activity was significantly increased in the presence of Ca+2 and surfactants and decreased by oxidizing agents, Cu+2, Zn+2, and Co+2 (p < 0.05). However, univalent ions Na+ and K+ did not show any significant effect on the activity of both trypsins (p > 0.05). The results of our study show that the properties of trypsin from beluga and sevruga are in agreement with data reported in bony fish and can contribute to the clear understanding of trypsin activity in these primitive species. beluga physicochemical properties sevruga trypsin digestive physiology Vice-Presidency of Research and Technology from Malayer University, Iran84/9-1-310 This work was funded by the Vice-Presidency of Research and Technology from Malayer University, Iran (grant number 84/9-1-310). pmc1. Introduction Beluga (Huso huso) and sevruga (Acipenser stellatus) are among the most important species of sturgeon fish (Acipenseridae) inhabiting the Caspian Sea with a high demand for products such as caviar, meat, skin, and cartilage . Today, sturgeons are considered a vulnerable group of fish species for different reasons such as overfishing for production of meat and caviar, water pollution, and destruction of their natural habitats . Therefore, in recent years, researchers have focused their studies on restocking and commercial rearing purposes. According to the Iranian Fisheries Organization report, the aquaculture production of sturgeon has increased from 363 t in 2009 to 2516 t in 2020 . A very important aspect in sturgeon farming industry, affecting its production efficiency and long-term sustainability, is the development of formulated compound diets for promoting growth and product quality. However, the ability of fish to digest compound diets is mostly related to the existence of the digestive enzymes in different parts of the gastrointestinal tract . Digestive enzymes reflect the capability of digestion in the organism under study and thus indicate the nutritional status at different stages of growth . Herein, analysis of digestive enzymes activity is regarded as a biochemical procedure which may contribute to generate valuable information for understanding the physiology of digestion in fish . This important issue can also help to define the requirements of fish for essential nutrients such as proteins, lipids, or carbohydrates . Among macronutrients, dietary proteins are key nutrients for fish growth, since proteins are the building blocks of muscle cells and organs. They occur in a great array of forms, and their nutritional value depends on their amino acid composition. As Moraes and Almeida, 2020 reviewed, the use of dietary proteins depends on a wide array of functional, biochemical, and genetic species-specific characteristics such as the age of organisms; the range of environmental factors (pH, dissolved oxygen, and ammonia levels); the amino acid profile of dietary protein; the digestible usable dietary energy levels; and the presence of antinutritional factors, among others. Protein digestion is conducted along the gastrointestinal tract by several proteases, with specific actions on the polypeptide chain. In gastric species, pepsin, trypsin, and chymotrypsin are the most important proteolytic enzymes in fish . As shown by Nolasco-Soria, 2021 , trypsin in combination with other alkaline proteases and peptidases such as chymotrypsin, aminopeptidases, and carboxypeptidases complete the acid predigestion conducted in the stomach, hydrolyzing protein residues and peptides to release free amino acids and small peptides for intestinal absorption; therefore, the activity of trypsin has been widely used as a valuable indicator of digestive capacity in fish, as well as a useful biomarker for its nutritional and physiological condition . According to surveys conducted in various species of fish, trypsin participates in activating trypsinogen and other zymogens in the intestine and plays an effective role in protein degradation of the consumed diet in the carnivorous fish up to 40-50% . Furthermore, trypsin quantification is essential for the design of in vitro digestibility protocols of feed ingredients and for the formulation of high digestible compound feeds for aquaculture fish species . Hence, a better understanding of the properties of trypsin is necessary to generate valuable information for protein degradation in the fish digestive tract. The characterization of trypsin, especially its physicochemical and biochemical properties, has been thoroughly studied from the intestine of various fish including grass carp (Ctenopharyngodon idellus), spotted goatfish (Pseudupeneus maculatus), grey triggerfish (Balistes capriscus), skipjack tuna (Katsuwonus pelamis), smooth hound (Mustelus mustelus), and Brazilian flounder (Paralichthys orbignyanus) . The activity of trypsin among several sturgeon species has been mostly studied during larval ontogeny in the members of the genus Acipenser such as A. transmontanus , A. fulvescens , A. oxyrinchus , A. baerii , A. persicus , A. nacarii , A. stellatus , and genus Huso such as H. huso . However, there are no studies evaluating the physicochemical and biochemical characteristics of trypsin in sturgeons; thus, this study attempts to characterize trypsin from beluga and sevruga, as two of the main sturgeon species from the Caspian Sea, for the first time. 2. Materials and Methods 2.1. Fish Samples Viscera from five specimens of beluga and sevruga (8.0 +- 0.4 kg; 95 +- 8 cm) were obtained from Saei sturgeon rearing center, Sari, Mazandaran, Iran. Fish were fed a commercial diet (crude protein 46%, crude lipid 16%, ash 8.5%, crude fiber 2.5%, and moisture 9%, Mazandaran Animal & Aquatic Feed Company, Semeskandeh Olya, Iran) and kept in fasting condition for 72 h before sampling. Those samples were packed in polyethylene bags, placed in ice with the sample/ice ratio of approximately 1:3 (w/w), and directly transported to the laboratory. Upon arrival, the intestine was separated from the rest of the collected viscera, washed with cold distilled water (4 degC), pooled, and stored at -80 degC for further analysis. 2.2. Preparation of Intestinal Crude Extracts for Trypsin Characterization The frozen intestine of beluga and sevruga was partially thawed in the refrigerator at 4 degC for 2 h. The samples were then cut into small pieces and homogenized in 50 volumes of 50 mM Tris-HCl buffer (pH 7.5, 10 mM CaCl2, 0.5 M NaCl) by a tissue homogenizer (Heidolph Diax 900, Sigma Co., St. Louis, MO, USA) at 4 degC for 2 min. The homogenate was then filtered with a cheese cloth to separate the floating fat phase and centrifuged for 45 min at 4 degC at 14,000x g by a refrigerated centrifuge (Hettich Benchtop Centrifuge Rotina 420R, Berlin, Germany). The resulting supernatant from each sample was collected, defined as intestinal crude extract (ICE), and then used throughout this study. 2.3. Reagents EDTA (Ethylenediaminetetraacetic acid), Pepstatin A, PMSF (phenylmethanesulfonyl fluoride), and sodium cholate were obtained from Molekula Co (Gillingham, UK). BAPNA (Na-benzoyl-DL-arginine-r-nitroanilide hydrochloride), ss-mercaptoethanol, BSA (bovine serum albumin), iodoacetic acid, saponin, SBTI (soybean trypsin inhibitor), TLCK (N-r-tosyl-L-lysine-chloromethyleketone), and TPCK (N-tosyl-L-phenylalanine chlorom ethyleketone) were purchased from Sigma Chemical Co (St. Louis, MO, USA). Molecular weight marker (PM 2700) was obtained from SMOBIO Technology, Inc. (Hsinchu, Taiwan). 2.4. Trypsin Assay To measure the enzyme activity in ICE, BAPNA was used as a substrate at a concentration of 1 mM in 50 mM Tris-HCl, 20 mM CaCl2 (pH 8.5) according to the method of Erlanger et al., 1961 . Each ICE (25 mL) was mixed with the prepared substrate (1250 mL) and incubated at 55 degC for 20 min. The reaction was terminated by adding 30% (v/v) acetic acid (250 mL) to the mixture and followed by measuring the trypsin activity at an absorbance of l = 410 nm using a spectrophotometer (UV-1601, Shimadzu, Kyoto, Japan). One unit of activity was defined as 1 mmol of r-nitroaniline released per min and calculated with the following equation :Trypsin activity unit/mL=Absorbance 410 nm x1000x mixture volume mL8800x reaction time minx0.025 where 8800 (cm-1 M-1) is the molar extinction coefficient of r-nitroaniline measured at l = 410 nm. 2.5. Protein Assay The concentration of protein in both ICEs was determined at l = 750 nm by using BSA (1 mg mL-1 as a standard) and Folin-Ciocalteau reagent according to the Lowry et al., 1951 method. 2.6. Characterization of Trypsin by SDS-PAGE Electrophoresis SDS-PAGE electrophoresis was performed to determine the protein pattern in ICEs from both sturgeon species . Each ICE was mixed at 2:1 (v/v) ratio with sample buffer (62.5 mM Tris-HCl pH 6.8, 2% SDS (w/v), 10% (v/v) glycerol, 0.3% (w/v) bromophenol blue and 5% (v/v) ss-mercaptoethanol) and boiled for 10 min. Thereafter, the ICEs (with protein concentration of 15 mg) were loaded onto the gel made of 4% stacking gel and 12% separating gel and the electrophoresis was run at a constant current of 15 mA using a vertical electrophoresis system (Bio-Rad Laboratories, Inc., Hercules, CA, USA). After the run, protein bands present in the gel were stained with 0.1% Coomassie Brilliant Blue (G-250) in methanol (35%) and acetic acid (7.5%) and unstained in methanol (35%) and acetic acid (7.5%). Casein-zymography was performed after electrophoresis for detection of proteases in both ICEs as described by Garcia-Carreno et al., 1993 . Both ICEs were submitted to native-PAGE electrophoresis in a same manner of SDS-PAGE where samples were not boiled, and SDS and reducing agent were removed. After the run, the gel was immersed in 50 mL of a casein solution (20 mg mL-1 in 50 mM Tris-HCl, pH 7.5) for 1 h at 4 degC with gentle agitation to allow diffusion of the casein into the gel. Thereafter, the gel was transferred to another solution (50 mL) containing casein (20 mg mL-1 in 50 mM Tris-HCl, pH 8.5, 10 mM CaCl2) for 20 min at 55 degC with continuous agitation. The gel was then stained with 0.1% Coomassie Brilliant Blue (R-250) in methanol (35%) and acetic acid (7.5%) and unstained in methanol (35%) and acetic acid (7.5%). The presence of proteolytic activities in both ICEs was indicated by the appearance of clear zones on the blue background of the gel, which meant that casein was digested by the targeted protease in these areas. To reveal the trypsin present in both ICEs, the inhibitory activity staining was used after the submission of both ICEs to native-PAGE electrophoresis as described by Ahmad and Benjakul with a slight modification. After the run, the gel was immersed in 30 mL of an SBTI solution (1 mg mL-1 in 50 mM Tris-HCl, pH 8.5, 10 mM CaCl2) for 30 min at 4 degC to allow diffusion of SBTI into the gel. Thereafter, the incubation of gel was performed for 40 min at 55 degC and followed by washing in cold distilled water and staining with 0.05% Coomassie Brilliant Blue (R-250) to appear inhibitory zones, indicating the presence of the trypsin in both ICEs. The molecular weight of the trypsin that appeared in both ICEs was estimated using wide-range molecular weight markers (PM2700, SMOBIO, Hsinchu, Taiwan) by calculating the trypsin Rf in comparison with those of protein markers. 2.7. Optimum Temperature and Thermostability To determine the optimum temperature for trypsin activity, the activity of this alkaline protease was measured in both ICEs at different temperatures, including 10, 25, 35, 45, 50, 55, 60, 65, and 70 degC after 20 min of incubation at pH 8.5, using 1 mM BAPNA as a substrate. For the thermostability test, both ICEs were incubated at the above-mentioned temperatures for 30 min and then cooled in an ice bath for assay of residual activity of the enzyme at pH 8.5 as described by Zamani et al., 2014 . 2.8. Optimum pH and Stability Different buffers in the pH range of 4.0 to 11.0 (50 mM acetic acid-sodium acetate for pHs 4-6; 50 mM Tris-HCl for pHs 7-9 and 50 mM glycine-NaOH for pHs 10-11) were used for determining the optimum pH for trypsin activity. Both ICEs were used, and they were incubated using1 mM BAPNA as a substrate after 20 min of incubation at 55 degC at different pHs. For the pH stability test, the remaining activity of the trypsin from each ICE was measured using 1 mM BAPNA as a substrate at 55 degC after being incubated at the above-mentioned pHs for 30 min . 2.9. Effect of Inhibitors Several protease inhibitors (0.01 mM pepstatin A, 0.05 mM SBTI, 1 mM iodoacetic acid, 2 mM EDTA, 5 mM TLCK, 5 mM TPCK, 5 mM ss-mercaptoethanol, and 10 mM PMSF) were prepared in the relevant solvents and incubated with an equal volume of each ICE at room temperature for 15 min. The remaining activity of the enzyme was then measured by 1 mM BAPNA as a substrate (at 55 degC, pH 8.5) and the percent inhibition was calculated according to the method of Khantaphant and Benjakul, 2010 . The trypsin activity of control was measured in the same manner without the presence of inhibitors and scored to 100%. 2.10. Effect of Metal Ions To investigate the effect of metal ions (5 mM) on the trypsin activity of both ICEs, univalent (K+, Na+) and divalent (Ca2+, Cu2+, Zn2+ and Co2+) cations were dissolved in 50 mM Tris-HCl (pH 8.5) and then incubated with an equal volume of each ICE for 30 min at room temperature. The residual activity of the enzyme was determined using 1 mM BAPNA as a substrate at 55 degC and pH 8.5 . The enzymatic activity of control was assayed without the presence of metal ions and taken as 100%. 2.11. Effect of Surfactants and Oxidizing Agents The effect of surfactants (anionic: SDS and sodium cholate; non-ionic: saponin and Triton X-100, all at 1%) and oxidizing agents (sodium perborate at a concentration of 1% and H2O2 at three concentrations of 5%, 10%, and 15%) on the trypsin activity was measured by incubation of the above-mentioned surfactants and oxidizing agents with an equal volume of each ICE for 1 h at 40 degC. The residual activity of the enzyme was then determined at 55 degC and pH 8.5 using 1 mM BAPNA as a substrate. The assessment of control enzymatic activity was conducted in a similar condition in the absence of chemicals and scored to 100% . 2.12. Statistical Analysis This study was conducted on the basis of a completely randomized design, and a one-way ANOVA was used for data analysis using SPSS package 22.0 (SPSS Inc., Chicago, IL, USA). All experimental assessments were performed in triplicate, and data was expressed as the mean +- standard deviation (SD). The comparison of means was carried out by Duncan's multiple range tests with a statistical significance at p < 0.05. 3. Results and Discussion Fish proteases such as trypsin have been the main objective of many of studies, but it is difficult to compare the results obtained in different species because the data are affected by the use of many different methodologies, the state of feeding of experimental animals (fed vs. starved fish), and the type of enzyme preparation (intestinal tissues alone vs. intestinal extracts with the intestinal content) . 3.1. Protein Pattern, Casein-Zymographyand Inhibitory Activity Protein pattern of ICE from beluga and sevruga is depicted in Figure 1a. Based on results obtained from the SDS-PAGE, a number of proteins with different molecular weights were shown in the ICE of both sturgeon species. The major bands of each ICE appeared between molecular weights comprised between 10 and 60 kDa. Casein-zymogram can be used as a highly sensitive and fast assay method for detecting nanograms of protein. The protease activity of both ICEs was demonstrated by casein-zymography as illustrated in Figure 1b. The clear bands, showing the presence of protease, appeared on the gel with different molecular weights. Based on the zymogram pattern, proteases present in ICE from beluga were observed in the range of molecular weights between 19 to 35 kDa, while those in the ICE of sevruga ranged from molecular weights of 19 to 45 kDa. Inhibitory activity staining for detection of trypsin in ICEs is depicted in Figure 1c. Results showed that a single band for each ICE clearly appeared on the gel with a molecular weight of 27.5 and 29.5 kDa for sevruga and beluga, respectively. In general, trypsins have molecular weights in the range of 20-30 kDa . In particular, different molecular weights for trypsins have been reported in various fish species such as 21.7 kDa for mrigal carp , 23.2 kDa for common kilka , 23.5 kDa for pirarucu , 24 kDa for small red scorpion fish , 21 and 24 kDa for liver of albacore tuna , 24 kDa for catfish , 24.4 kDa for gulf corvina , 25 kDa for Monterey sardine , 26 kDa for common dolphinfish , 27 kDa for zebra blenny , 28.8 kDa for sardinelle , 29 kDa for Atlantic bonito , 38.5 kDa for tambaqui , and 42 kDa for skipjack tuna . However, several reasons such as different habitat and climate, autolytic degradation, and genetic variation among fish species may explain why trypsins from various sources have different molecular weights . 3.2. Optimum Temperature and Thermostability Enzymes are one of the main biological macromolecules and their maximum activity depends on an optimum temperature to make them functional. Figure 2a revealed that optimum temperature of the trypsin in ICE prepared from beluga and sevruga was found to be 55 degC, although 92.70% of the maximum activity of the enzyme was still maintained at 60 degC for both sturgeon species. However, an obvious decrease in the trypsin activity of both ICEs was observed at temperatures above 60 degC, probably due to thermal inactivation of this enzyme caused by protein unfolding . Similar optimum temperature (55 degC) was recorded for trypsins in skipjack tuna , gilthead seabream , sardinelle , and silver mojarra . Optimum temperature of trypsin for both sturgeon species was higher than values reported for cold-water fish such as Atlantic cod (Gadus morhua) , grey triggerfish , lane snapper (Lutjanus synagris) , and Japanese sea bass (L. japonicus) indicating optimum temperatures over a range of 40-45 degC. These differences could be attributed to the temperature of the fish habitat or experimental conditions used in assessments . The optimum temperature for enzyme maximum activity may be interesting for comparative physiological studies, even though such data offer limited information on enzyme activity under normal rearing conditions. Although fish trypsins are mostly unstable at temperatures higher than 40-50 degC, their thermal stability is well known to be at temperatures below 40 degC . Trypsin thermal stability from ICE of beluga and sevruga is displayed in Figure 2b. As can be observed in this figure, the stability of both trypsins was highly maintained up to 50 degC with a remaining activity of 90.2% and 91.7% for sevruga and beluga, respectively. A gradual decrease in the activity of both trypsins was recorded at 55 degC, whereas enzymatic activity sharply decreased at 60 degC. After heating the ICEs at 70 degC, the relative activities for both trypsins were only about 0.9% and 1.6% of their initial activity for sevruga and beluga, respectively. These results were in accordance with those of sardinelle, common kilka, mrigal carp, and pirarucu, which were exhibited to be stable up to 50 degC . The trypsins from beluga and sevruga showed to be more stable at high temperatures in comparison with those reported for the Monterey sardine, chinook salmon, bluefish, Tunisian barbell, and common dolphinfish that the enzymatic activity was rapidly lost at temperatures above 40 degC . In general, thermostability of the trypsin enzyme might vary by some factors such as fish species and experimental conditions . From a biological point of view, it is difficult to deduce any advantage for beluga and sevruga in possessing proteases showing different resistances to heating, since the normal temperature of water rarely exceeds 21-24 degC. Nevertheless, from a biotechnological perspective, it may be interesting to have information about active and easily denaturalizable proteases potentially useful in the feed industry . 3.3. Effect of pH on Trypsin Activity and Stability The results observed from the effect of pH on the activity and stability of trypsin from beluga and sevruga are illustrated in Figure 3. Trypsins from both species had a maximal activity at pH 8.5 . Trypsin activity was dramatically reduced at pH values ranging from 4.0 to 5.0. Our results showed that the stability of trypsin from both sturgeon species was highly preserved at pH values comprised between 5.0 and 11.0 with activity values of 75% for beluga and 80% for sevruga. The high ranges of pH may change the net charge and conformation of an enzyme and inhibit to bind to the substrate properly, resulting in the abrupt loss of enzymatic activity . Trypsins are mainly known to have more activity within a range of pH values comprised between 7.5 and 10.5 . The optimum pH (8.5) recorded for trypsin in both sturgeon was similar with results reported for trypsins from the brownstripe red snapper viscera and the albacore tuna hepatopancreas , whereas both trypsins indicated the lower optimum pH than those recorded for the Japanese sea bass, gilthead seabream and common dentex, and the pirarucu . However, optimum pH may differ depending upon the experimental conditions such as concentration and type of substrate, temperature, and type of metal ions . For instance, Martinez et al., 1988 showed that the trypsin from pyloric caeca of the anchovy had the optimum pHs of 8.0 and 9.5 for the hydrolysis of BAPNA and casein, respectively. The effect of pH on the trypsin stability in both ICEs is displayed in Figure 3b. The stability of both enzymes was considerably retained between pH 6.0 to 11.0. Trypsin activity was lost about 63.15% and 69.26% at pH 4.0 in sevruga and beluga, respectively, while the loss of the enzyme activity at pH 5.0 was recorded by 34.13% and 35.84% for sevruga and beluga, respectively. However, trypsin in ICE of sevruga and beluga lost only 1.19% and 1.51% of its activity at pH 8.5, respectively. Similar behavior was reported for trypsins from common kilka , common dolphinfish , and zebra blenny which retained 80-100% of the activity at pH ranges of neutral and alkaline. The high catalytic activity of the trypsin is observed in alkaline pHs, and its stability at a particular pH may be linked to the net charge of the enzyme at that pH . 3.4. Effect of Inhibitors on Trypsin Activity The sensitivity of protease enzymes to various inhibitors is a valuable tool for their proper functional characterization . Based on their nature, inhibitors can be classified into two classes: chemical inhibitors and protein inhibitors . A trypsin inhibitor is a type of serine protease inhibitor that reduces the biological activity of trypsin thereby rendering it unavailable to bind with proteins for the digestion process . Therefore, it can be considered important to characterize the effect of different inhibitors on the trypsin activity. Table 1 shows the effect of different inhibitors on the activity of trypsin from beluga and sevruga. As it is shown in this table, a serine protease inhibitor such as PMSF inhibited 39.11% and 36.29% of the trypsin activity in sevruga and beluga ICE samples, respectively. Both enzymes were completely inhibited by trypsin specific inhibitors such as SBTI and TLCK, while a chymotrypsin-specific inhibitor (TPCK) did not show any inhibitory effect on their enzymatic activity (p > 0.05). Furthermore, a metalloproteinase inhibitor (EDTA) and a disulfide bond reducing agent (ss-mercaptoethanol) had a partial inhibitory effect on trypsin activity in both sturgeon species, although the inhibition rates varied between both species. In particular, trypsin from sevruga was inhibited by ss-mercaptoethanol (25.33%) and EDTA (23.55%) more than those in beluga (22.84 and 21.06%, respectively) where no significant difference was shown between both species (p > 0.05). Results from EDTA indicate the high dependence of trypsin activity from both sturgeon species on divalent cations . However, an aspartic proteinase inhibitor (Pepstatin A) and a cysteine proteinase inhibitor (iodoacetic acid) exhibited a negligible inhibitory effect on the trypsin activity of both species. Similar results have been observed in other fish species . For instance, Khangembam and Chakrabarti, 2015 reported that trypsin activity from the digestive system of mrigal carp was inhibited by SBTI and TLCK. SBTI is a single polypeptide chain that acts as a reversible competitive inhibitor of trypsin and forms a stable, enzymatically inactive complex with trypsin, resulting in reduction of the enzyme availability . TLCK is an irreversible inhibitor of trypsin and trypsin-like serine protease that deactivates these enzymes through the formation of a covalent bond with histidine residue in the catalytic site of the enzyme and blocks the active center of the enzyme for binding to substrate . As reported by several authors , PMSF strongly inhibited the activity of trypsin from viscera of common kilka, pirarucu, and zebra blenny, respectively, whereas TPCK had no effect on the enzyme activity from common kilka . The trypsin activity from the intestine of common dolphinfish was partially inhibited by b-mercaptoethanol and EDTA , while the trypsin activity from liver of albacore tuna was not reduced in the presence of pepstatin A and iodoacetic acid . 3.5. Effect of Metal Ions Metal ions have a key role in the activity regulation of many enzyme-catalyzed reactions . Our results on the effect of metal ions on the trypsin activity in beluga and sevruga are detailed in Table 2. No significant effect on the activity of both enzymes was found in the presence of univalent cations Na+ and K+ (p > 0.05). The enzymatic activity of trypsin in both species was significantly reduced by divalent cations Cu2+, Zn2+ and Co2+, whereas Ca2+ significantly enhanced the activity of both trypsins (p < 0.05). Similar results on the effect of Ca2+ on the trypsin activity were also observed in common kilka, common dolphinfish, and zebra blenny . The attachment of Ca2+ to the active site of serine proteases such as trypsin not only increases the stability of the enzyme structure, but it also protects the enzyme from self-digestion . The enzymatic activity of trypsin in common dolphinfish was reduced by 82% and 81% by Zn2+ and Cu2+, respectively , while 100% of enzymatic activity of tryspin from zebra blenny was lost in the presence of Zn2+ and Cu2+ . In common kilka , no inhibition was observed in the trypsin activity in presence of Na+ and K+. Differences in percent inhibition might be linked to species diversity, environmental adaptations and feeding habits of fish . 3.6. Effect of Surfactants and Oxidizing Agents Surfactants are the most widely used groups of compounds today, with wide application in industry and household. These are unique substances that contain hydrophobic and hydrophilic moieties within their molecule and find enormous applications in biology. Oxidizing agents such as sodium perborate and H2O2 are also used in the detergent industry as bleaching agent. Surfactants and oxidizing agents may be harmful or even toxic to aquatic organisms. These compounds can penetrate through tissues and bind to biomolecules, such as enzymes, causing changes in cellular activity . As reviewed by Rubingh, 1996 , surfactants can influence the activity of enzymes in two ways. Firstly, by binding to the enzyme, surfactants can influence intrinsic enzyme properties such as the secondary and tertiary structure or flexibility, and thereby, affect its ability to serve as a catalyst. A less direct, but equally important, way in which surfactants affect enzyme activity is by changing the environment in which the enzyme functions. It is well-known that SDS disrupts non-covalent bonds within and between enzymes, denaturing them, and resulting in the loss of their native conformation and function , whereas saponin, Triton X-100, and sodium cholate are the non-denaturing surfactants . Hence, characterizing the effect of these chemical compounds on trypsin activity is of relevance for proper characterizing its activity. The results on the effect of various surfactants and oxidizing agents on the trypsin activity in sevruga and beluga are shown in Table 3. A significant increase in the activity of both trypsins was observed after incubation for 1 h at 40 degC in the presence of surfactants tested, including saponin, sodium cholate, and Triton X-100 at final concentrations of 1% (p < 0.05). Both trypsins were highly unstable against sodium dodecyl sulfate (SDS), in which trypsins from sevruga and beluga significantly lost about 94% and 97% of their activity in the presence of 0.1% SDS, respectively (p < 0.05). Similar results were found in trypsins of other fish species in the presence of saponin, sodium cholate, Triton X-100 and SDS . The obtained results on the effect of oxidizing agents on both trypsins showed that the enzymatic activity was reduced in the presence of sodium perborate (1%) in sevruga and beluga by 22.23% and 24.37%, respectively. The activity of both enzymes was also decreased significantly with an increase in H2O2 concentrations from 5% to 15%, as described in Table 3 (p < 0.05). Trypsin from sevruga showed significantly higher activity than trypsin from beluga in the presence of H2O2 ranging from 5% to 15%, indicating that trypsin from sevruga was more tolerant to H2O2 than trypsin from beluga. The biochemical and structural properties of enzyme can affect its ability as a catalyst in presence of oxidizing agents . These results showed that trypsins from sevruga and beluga were more stable against H2O2 than trypsins from grey triggerfish and zebra blenny , whereas most proteases have shown to be unstable in the presence of oxidizing agents like hydrogen peroxide . 4. Conclusions The results of our study indicated that trypsin from intestine of beluga and sevruga had similar properties to trypsins from bony fish. The enzyme had an optimum temperature of 55 degC and thermal stability was maintained over 90% up to 55 degC. This alkaline protease had an optimum pH of 8.5 and showed to be tolerant in the pH range of 6.0 to 11.0 in both studied sturgeon species. The molecular weight of trypsin for sevruga and beluga was estimated to be 27.5 and 29.5 kDa, respectively, as data from inhibitory activity staining indicated. Both trypsins were inhibited by main specific inhibitors, SBTI and TLCK. Additionally, the enzymatic activity of trypsins was still detected after 1 h in the presence of surfactants and oxidative agents. Information provided in this manuscript related to trypsin activity for beluga and sevruga based on changes in the activity of this alkaline protease based on a tested range of pH and temperature values, and presence of potential inhibitors, ions and cations may be considered a preliminary step to design in vitro tests for the assessment of protein digestibility in these species. Acknowledgments We would like to express our sincere gratitude to laboratory staffs of Fisheries Department of Natural Resources and Environment Faculty of Malayer University for helpful assistance. Author Contributions Conceptualization and methodology, A.Z.; writing--review and editing, A.Z. and E.G.; investigation and writing--original draft, M.K.; data analysis and measurement of physicochemical properties of the enzyme, A.A.K., M.H.N., A.S. and M.E. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement This study conformed to the current Iranian law regarding the care and use of laboratory animals and was approved by the Animal Ethical Committee of Malayer University (Code: IR.UMSHA.REC.1397.994). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Figure 1 SDS-PAGE (a), zymography (b), and inhibitory activity staining (c) of the intestinal crude extract (ICE) of Huso huso and Acipenser stellatus. (a): Molecular weight marker (M); ICE from Huso huso intestine (B); ICE from Acipenser stellatus intestine (S). Coomassie blue G-250 (0.1%) was used for staining proteins from SDS-PAGE. Zymogram activity and inhibitory activity staining were stained by using 0.1% Coomassie blue R-250. Figure 2 (a) Optimum temperature: the enzymatic activity of both trypsins was measured at different temperatures at pH 8.5 using BAPNA as a substrate; (b) thermostability: residual activity of both enzymes was determined at 55 degC and pH 8.5 after incubating at different temperatures for 30 min using BAPNA as a substrate. Figure 3 (a) Optimum pH: the enzymatic activity of both trypsins was determined at different pHs at 55 degC using BAPNA as a substrate; (b) pH stability: residual activity of both enzymes was measured at 55 degC and pH 8.5 after incubating at different pHs for 30 min using BAPNA as substrate. animals-13-00853-t001_Table 1 Table 1 Effect of various inhibitors on the activity of trypsin from Huso huso and Acipenser stellatus. Inhibitors Concentration Inhibition (%) Huso huso Acipenser stellatus Control - 0.0 +- 0.00 a 0.0 +- 0.00 a PMSF 10 mM 36.29 +- 0.39 c 39.111 +- 0.45 c SBTI 0.05 mM 99.81 +- 0.54 d 99.29 +- 0.49 d TLCK 5 mM 99.19 +- 0.57 d 99.51 +- 0.47 d TPCK 5 mM 0.00 +- 0.00 a 0.00 +- 0.00 a Pepstatin A 0.01 mM 0.51 +- 0.003 a 0.89 +- 0.002 a Iodoacetic acid 1 mM 0.25 +- 0.002 a 0.44 +- 0.003 a EDTA 2 mM 21.06 +- 0.36 b 23.55 +- 0.51 b ss-Mercaptoethanol 5 mM 22.84 +- 0.41 b 25.33 +- 0.37 b Each intestinal crude extract (ICE) was incubated with same volume of inhibitor at room temperature for 15 min and the enzyme activity was determined at pH 8.5 and 55 degC. The control was prepared with similar conditions in absence of inhibitors. Data were represented by mean +- standard deviation and compared by Duncan's multiple-range test. Different superscripts in the same column show statistical difference while there is no significant difference in the same row (p < 0.05). animals-13-00853-t002_Table 2 Table 2 Effect of various metal ions on activity of trypsin from Huso huso and Acipenser stellatus. Metal Ions Concentration Residual Activity (%) Huso huso Acipenser stellatus Control - 100 +- 0.00 d 100 +- 0.00 d KCl 5 mM 99.6 +- 1.05 d 99.2 +- 0.92 d NaCl 5 mM 99.3 +- 1.03 d 99.5 +- 1.01 d CaCl2 5 mM 107.21 +- 0.81 e 105.32 +- 0.98 e CuCl2 5 mM 48.31 +- 0.88 a 44.58 +- 0.96 a ZnCl2 5 mM 67.79 +- 1.15 b 64.83 +- 1.23 b CoCl2 5 mM 76.69 +- 0.85 c 74.77 +- 1.05 c Univalent and divalent metal ions were incubated with same volume of each intestinal crude extract (ICE) at room temperature for 30 min and residual activity of the enzyme was measured at pH 8.5 and 55 degC. The control was prepared with similar conditions without metal ions and scored as 100%. Data were represented by mean +- standard deviation and compared by Duncan's multiple-range test. Different superscripts in the same column show statistical difference while there is no significant difference in the same row (p < 0.05). animals-13-00853-t003_Table 3 Table 3 Trypsin activity from Huso huso and Acipenser stellatus in presence of surfactants and oxidizing agents. Chemicals Concentration Residual Activity % Huso huso Acipenser stellatus Surfactants Control - 100 +- 0.00 A d 100 +- 0.00 A d Triton X-100 1% 108.81 +- 1.62 A e 112.55 +- 1.11 A e SDS 1% 2.79 +- 0.21 A a 5.77 +- 0.33 B a Sodium cholate 1% 132.23 +- 1.12 A j 197.77 +- 0.99 B j Saponin 1% 126.14 +- 1.06 A f 128.44 +- 1.46 A f Oxidising agents Sodium perborate 1% 75.63 +- 1.07 A c 77.77 +- 0.97 A b H2O2 5% 70.30 +- 1.02 A c 87.55 +- 1.02 B c 10% 64.97 +- 1.19 A c 84.55 +- 0.73 B c 15% 40.35 +- 0.65 A b 73.77 +- 0.91 B b Each intestinal crude extract (ICE) was incubated with same volume of the chemicals for 1 h at 40 degC and residual activity of the enzyme was measured at pH 8.5 and 55 degC. The control was prepared with similar conditions without chemicals and scored as 100%. Data were represented by mean +- standard deviation and compared by Duncan's multiple-range test. Different capital letters in the same row and different superscripts in the same column show statistical difference (p < 0.05). Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000240 | Guinea pigs are important animal models for human disease, and both outbred and inbred lines are utilized in biomedical research. The optimal maintenance of guinea pig colonies, commercially and in research settings, relies on robust informed breeding programs, however, breeding data on specialized inbred strains are limited. Here, we investigated the effects of parental age, parity, and pairing approaches on mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days in strain 13/N guinea pigs. Our analysis of colony breeding data indicates that the average litter size is 3.3 pups, with a 25.2% stillbirth rate, a failure-to-thrive outcome in 5.1% of pups, and a 10 day survival rate of 69.7%. The only variable to significantly affect the reproductive outcomes examined was parental age (p < 0.05). In comparison to adults, both juvenile and geriatric sows had lower total fetus counts; juvenile boars had a higher percentage of females in litters, and geriatric boars had a lower 10 day survival rate of pups. These studies provide valuable information regarding the reproductive characteristics of strain 13/N guinea pigs, and support a variety of breeding approaches without significant effects on breeding success. guinea pig breeding reproduction pairing strategy age sex ratio litter size CDC Emerging Infectious Disease Research CoreThis work was supported in part by CDC Emerging Infectious Disease Research Core funds. pmc1. Introduction Guinea pigs are important animal models for human disease and have been used for approximately 200 years. Their first uses included being in a study measuring heat production during respiration , and they were later used as models for infectious diseases such as tuberculosis and diphtheria . While the use of guinea pigs has declined since peaking in the 1960s, they continue to be utilized today to model pulmonary, sexually transmitted, ocular, aural, and gastrointestinal diseases of bacterial or viral origin . Additionally, guinea pigs have hemomonochorial placentation, as do humans, as well as a gestational period that can easily be divided into distinct trimesters, supporting their role as a model for reproductive toxicology and other pregnancy-related health issues . Strain 13/N guinea pigs, which also appear in the literature as strain 13 or 13N, were originally developed in the early 1900s by the United States Department of Agriculture (USDA) . This inbred strain serves as a critical small animal model of human disease; strain 13/N guinea pigs are used to study various conditions, including autoimmune thyroiditis and osteoarthritis , and are also used as models of disease for highly pathogenic human viruses. Strain 13/N guinea pigs are susceptible to severe and fatal disease following infection with pathogenic arenaviruses, including Lassa and Lujo viruses , and recapitulate many characteristics of infection in humans. As such, these guinea pigs have been essential for investigations of viral pathogenesis, therapeutic screening, and vaccine development for these high-consequence, high-containment agents. In addition, differential susceptibilities to disease in inbred guinea pig strains allow for investigations of associated hereditary deficiencies and biomarkers . Despite their notable utility, currently in the United States, there is only a modest number of strain 13/N guinea pig colonies in institutions, limiting the supply of these essential animals. One of the challenges in maintaining colonies of strain 13/N guinea pigs is their breeding, since 13/N guinea pigs have smaller litter sizes and slower growth rates when compared to outbred Hartley guinea pigs . Maintaining a healthy animal population requires knowledge of herd health and efficient reproductive management. The literature generally describes the sexual maturity and breeding characteristics of guinea pigs as follows: male guinea pigs (boars) usually mature sexually and can mate as young as 2-3 months of age, and female guinea pigs (sows) typically mature sexually at 2 months of age (55 to 70 days). However, both males and females can mature and be fertile even earlier. For guinea pig breeding, most recommendations are for the sow's first breeding to occur before 6-7 months of age. Sows that reach adulthood without a prior pregnancy may not be able to deliver their young normally, due to a normal stiffening of the fibrocartilaginous pubic symphysis, resulting in dystocia when the pubic symphysis fails to relax over the course of gestation. Females spontaneously ovulate, and can have estrous or fertile periods at any time of the year, but they are most common in the spring . The estrous cycle length is 16 days (13-21 day range) . A female is fertile for about 6 to 11 h, most often during night hours . Female guinea pigs begin a new estrous cycle 2 to 10 h after giving birth . The guinea pig gestation period is 59 to 72 days. The litter size ranges from one to eight pups, but a litter of two to four is more common. A female can give birth to up to five litters per year when continuously paired with a male . Previous studies of guinea pigs have shown that various factors, including maternal weight at conception, seasonality, social stability, and concurrent lactation, can impact reproductive parameters, such as the litter size, sex ratio, and onset of puberty . Similarly, maternal age, maternal weight, postpartum estrus breeding , concurrent lactation , and seasonality have been reported to affect the litter size and pup sex ratio in other rodents. To help safeguard this valuable animal model, the aim of this study was twofold: to characterize breeding outcomes, such as the birthing interval, litter size, and still birth rate, and to analyze factors influencing reproduction results in strain 13/N guinea pigs, with a focus on litter size, litter sex ratio (examined as the percentage of females in each litter), and 10 day survival rate. The goal of these analyses was to identify parameters and methods to improve breeding efficiency, and to encourage positive reproductive outcomes in strain 13/N guinea pig colonies. 2. Materials and Methods 2.1. Ethics Statement All animal procedures were approved by the CDC Institutional Animal Care and Use Committee and conducted in accordance with the Guide for the Care and Use of Laboratory Animals at an AAALAC International-accredited facility. 2.2. Guinea Pigs and Breeding Strategy Strain 13/N male and female guinea pigs were housed under ABSL-2 conditions, in conventional racks or floor pens segregated by sex, in a climate-controlled laboratory with a 12:12 h light cycle. Animals were provided with ad libitum feed [Guinea Pig Diet 5025; LabDiet, www.labdiet.com (assessed on 21 January 2023), containing min 18% protein, min 4% crude fat, and max 16% crude fiber] and water, Timothy hay daily, and fresh vegetables three times a week. Over the study period, and for the length of time we have maintained the colony, the husbandry practices have remained largely consistent. The animals have been housed in the same facility (same climate and noise environment) with comparable feed and enrichment approaches. When actively breeding, animals were kept as a male-female pair, in a trio, with 2 females to 1 male, or in a quad, with 3 females to 1 male. Active breeding groups may be maintained in standard rack caging or in smaller, partitioned floor pens that meet regulations for enclosure size. The colony was acquired in 2012 and began with 22 animals representing 10 sibling breeding groups from the subsequently depopulated colony at Iowa State University. Previously, the strain was maintained through continuous housing of male-female sibling pairs from birth; however, in our facility, juveniles are separated by sex at weaning, typically at 4-8 weeks old, and then selectively paired later. When animals were paired, males were removed after 6-8 weeks, or were co-housed with the female from the time of pairing through to parturition, to capitalize on the fertile post-partum estrus. Females were examined for pregnancy, beginning 4-6 weeks after pairing, by abdominal palpation and/or abdominal radiographs. Spontaneous abortions were recorded, as detected by the presence of significant vaginal bleeding and/or expulsion of fetal membranes, and were confirmed by veterinary staff. 2.3. Statistical Analyses Kernel density estimation was used to assess the distribution of the ages for both sows and boars at delivery and the weights of sows by age at delivery. Breeding sows and boars were primarily young adults, although pairings also included juvenile and geriatric animals; a comparable proportion of age categories was observed between the sexes. ANOVA was used to analyze the differences in mean total fetus count, litter sex ratio, and survival rate after 10 days between juvenile (0 through 150 d), adult (151 through 900 d), and geriatric (older than 900 d) guinea pigs, based on the age, weight, and parity of the sow at delivery. The analyses were also conducted separately, considering boar age for each parameter. Differences were analyzed via ANOVA to account for other effects, and to determine which were significant. For all analyses, the probability that the null hypothesis was correct (p-value) was compared to a of 0.05. 3. Results 3.1. Data Collection and Summary of Breeding Characteristics The following breeding data were collected when available for pairings between 2012 and 2021: the age of sow and boar at pairing and at the birth of offspring, breeding scheme type (male-female pair, trio, or quad), length and number of pairing attempts, number of pregnancies, pairing-to-birth interval (days), number of pups (including stillbirths and failure to thrives within 10 days of birth), and sex of the weaned pups. The dataset represents a total of 267 litters and 296 breeding events, involving 168 sows and 100 boars. Not all data were recorded for all pairings or pregnancies. Thus, only those pairings or pregnancies for which the parameter of interest was available were included in corresponding analyses. Mean (median) age at primiparous parturition in the colony is 219.6 (213.5) days (n = 157). The oldest unassisted first birth was by a sow who was 388 days old (paired at 279 days of age). Amongst animals paired since birth, the mean (median) first birth occurs at 149 (136) days (n = 14). The youngest recorded birth was from a 105 day-old sow, and the youngest sire was 134 days old at time of birth. A small number of animals in the colony have been known to successfully breed after 3 years of age, with the oldest delivery overall in the colony being by an 1895 day-old sow . Litter size was normally distributed from one to seven pups, with most litters between three and four pups . The average litter size was 3.3 pups, with a 25.2% stillbirth rate, with failure-to-thrive (not stillborn but do not survive 10 days) occurring in 5.1% of pups, and a 10 day survival rate of 69.7% (includes stillborn and failure-to-thrive). In this breeding cohort, there were 27 (10.1%) litters in which all pups were stillborn (range of one to five stillborn pups in litter; 81 pups total); whereas 87 (32.6%) litters had a mix of live and stillborn pups (range of one to four stillborn pups in litter, representing 16.7-80% of total litter size; 174 pups total). Additionally, there were 153 (57.3%) litters in which no pups were stillborn, with a range of one to five pups in the litter, 439 pups total. Overall, two pups were weaned per breeding attempt (590 pups weaned out of 296 total pairings). As biased sex ratios can reduce the size of the breeding population, tracking the operational sex ratio is critical for the conservation and reproductive management of both wild and laboratory populations . The male-to-female birth ratio of strain 13/N guinea pigs was evenly split among weaned animals, with 296 females:294 male offspring from 181 weaned litters (leaving an additional 33 litters where no pups survived to weaning). The largest number of litters by a sow in a year was three (four sows), with most sows bearing one to two litters per year. To further characterize breeding outcomes in our colony by age at delivery, the breeding population was investigated by using three broad age categories, as previously described for strain 13/N guinea pigs : 0 through 150 d for juveniles, 151 through 900 d for adults, and older than 900 d for geriatric adults (Table 1 and Table 2). 3.2. Effects of Parental Age on Breeding Outcomes To investigate the factors contributing to improved breeding outcomes, a series of analyses were conducted, examining the age at delivery (sow or boar), total fetus count, percentage of female pups in a litter, and survival rate after 10 days. ANOVA was used to analyze the differences in each parameter between adult guinea pigs and juvenile or geriatric ones, with category designation based on the age at delivery (Table 3 and Table 4). Factor effect Models were used to compare averages for juvenile and geriatric guinea pigs directly to those for adult animals. The analyses were conducted separately for sows and boars, for each measure. As age and weight are generally correlated, we also looked at weight separately as a potential confounding factor. Reproduction represents the most energetically demanding life history stage in mammalian females. Adequate and balanced dietary intakes of specific macronutrients are of major importance to ensure an appropriate energy supply for maintaining reproductive performances . To eliminate potential bias in the age analysis due to a weight effect (as weight may reflect adequate or optimal energy balance), a kernel density estimation of sow weights was broken down by age category (scaled by pregnancies). The weight distribution of sows was normal, with a larger left tail partly attributed to juvenile pregnancies . No distributional difference was detected, neither in the adult population nor in juvenile or geriatric populations. We also evaluated the correlation of weight with total fetus count (0.0069, p-value = 0.41), to ensure that the age of the sow was the significant factor and not a matter of weight. Overall, adult sows had a higher total fetus count (3.28, n = 240), on average, than either juvenile (2.21, n = 19) or geriatric (1.86, n = 7) sows, but the offspring of juvenile sows maintained a higher 10-day survival rate (0.86, n =19) than that of adults (0.71, n = 240). Geriatric sows had the lowest 10 day survival rate (0.42, n = 7) of the different age brackets. Adult sows had a significantly lower percentage of female pups (0.478, n = 211) than juvenile (0.696, n = 17) and geriatric (0.556, n = 3) sows. Overall, pairing with adult boars led to a higher total fetus count (3.24, n = 243), on average, than with either juvenile (2.57, n = 7) or geriatric (2.4, n = 10) boars. As seen with the sows, offspring of juvenile boars had the highest 10 day survival rate (0.79, n = 7), with those of adults (0.72, n = 243) being slightly lower and geriatric boars (0.45, n = 10) being significantly lower; the pairing with adult boars (0.489, n = 215) led to a significantly lower percentage of female pups than with juvenile boars (0.806, n = 6). The percentage of female pups from geriatric boars (0.183, n = 3) was even lower than seen with the adults, but did not reach statistical significance. As the age of both the sows and boars had apparent impacts on the parameters of total fetus count, percentage of female pups in the litter, and 10 day survival rate, we sought to isolate the characteristics with the greatest effects by using ANOVA, including both sow and boar age categories. We started with the factors that were significant from the sow and boar individual analysis, and removed the factors that were now insignificant in the combined analysis in a stepwise manner, removing the least significant factor at each step until only the significant factors remained. When we added both sows and boars together, some of the factors went away. This phenomenon happens when factors are somewhat colinear with each other--in this case, adult sows and adult boars. Even though factors were significant when we looked at sows and boars separately, the factors we arrived at below are the ones that best account for the differences for each measure (Table 5). For total fetus count, values for both juvenile sows and geriatric sows remained significantly below the average count, while the geriatric boars were not a significant factor for the pooled analysis. Regarding the percentage of female pups, only the juvenile boars remained as a significant factor, having a 32% higher rate than the average. For the 10 day survival rate, geriatric boars were the only significant factor, having a 28% lower rate. These were the factors that were most responsible for the observed differences, but with larger sample sizes (particularly for geriatric guinea pigs), the excluded factors might be found to be significant. 3.3. Effects of Parity on Breeding Outcomes Parity was reported to have a significant effect upon litter size in mice, particularly for litters conceived during postpartum estrus, but also for those conceived after lactational anestrus . A study in small cohorts of mice (n = 18-22), with between 1 and 20 litters per individual, reported an initial increase in litter size after a primiparous litter, followed by a plateau period, and finally a period of linear decline, in which the mean number of young born decreased by one in each successive litter . This decline was attributed to factors causing increased embryonic loss, rather than resulting from a diminished supply of eggs. To examine this phenomenon in our colony, breeding outcomes were analyzed based on sow parity. Sows in our dataset had a range of one to five total pregnancies (Table 4). Most sows had a single pregnancy, and the frequency of pregnancy for multiparous sows decreased as the total number of pregnancies increased (Table 6). Using these groupings, we looked at the impact of the number of pregnancies per sow on the total fetus count, percentage of female pups in a litter, and survival rate after 10 days. Because of the limited number of sows having three or more pregnancies, we looked at the averages across all pregnancies for the first, second, third, etc., and ANOVA was used to compare subsequent pregnancies to the initial one. In our sample cohort, the number of pregnancies was not found to have a significant impact on any of these measures (Table 6). 3.4. Effects of Pairing Strategies on Breeding Outcomes Another component of this study was to evaluate the potential impacts of management strategies on breeding efficiency, including back-to-back breeding using the fertile post-partum estrus period, as well as pair vs. harem mating schemes. Our facility does not check for copulatory plugs as standard practice in our breeding program. Thus, we evaluate the "birthing interval", the length of time from mate pairing to birth, as a substitution for true gestational length, keeping in mind the 16 day estrous cycle of guinea pigs. In back-to-back breeding, which takes advantage of the fertile post-partum estrus, an immediate pregnancy consists of a birth-to-birth interval equivocal to gestation length, with a median of 71 days. From our data, the birthing interval of back-to-back breeding is shorter, on average, than that of new pairings (81 days). We compared 45 pairings, where the breeding couple were not separated, to 201 new pairings (separated prior to pairing), using two sample t-tests to analyze the percentage of female pups, 10 day survival rate and total fetus count (Table 7). We found no significant differences between the two breeding strategies. Another breeding strategy involves the pairing approaches, which include: (1) monogamous pairs (one male and 1onefemale), which is common for strains with good fecundity; (2) a mating trio (one male, two females), which maximizes cage space for breeding, and mothers assist in raising each other's pups; (3) quad (harem) mating, which houses three females in a cage with one male (only one male per cage is allowed). For our analyses, breeding attempts were classified as male-female pairs (pair), two females to one male (trio), or three females paired with one boar (quad). We compared the trio and quad pairing strategies to the male-female pairs using ANOVA, in order to compare the birth interval, percentage of females in the litter, 10 day survival rate and total fetus count (Table 8). There were 236 total pairings with 112 pairs, 105 trios, and 19 quads. The different pairing strategies resulted in no significant differences between any of these variables. 4. Discussion Here, we investigated the effects of a variety of parameters on breeding outcomes in a colony of inbred strain 13/N guinea pigs. Work with this lineage has provided critical advancements in therapeutic and vaccine development for human disease. These and other guinea pig inbred strains serve as highly translatable models for a wide variety of human biomedical research fields. To ensure the availability of these critical animals and to help optimize breeding outcomes in the colony, we characterized breeding trends, such as birthing interval, average litter size, and stillbirth rate. We further investigated several parameters that could be optimized in the future of the program, namely, the age of the parents, parity, and pairing strategies. Overall, breeding characteristics were comparable to other guinea pig strains, including an average litter size that favored triplets, and a stillbirth rate that is just slightly higher (25.2%) than the 22% rate reported in long-haired guinea pigs (Cavia aperea f. porcellus) . Of all variables investigated, parental age was the only factor associated with significantly different reproductive outcomes. In general, adult sows had a higher total fetus count than either juvenile or geriatric sows, but juvenile sows maintained a higher 10 day survival rate than adults, suggesting that there is a tradeoff consideration in age selection, and that both age categories can contribute to colony maintenance. Reproductive gain appears to wane in geriatric sows, which had the lowest 10 day survival rate of the age brackets. These data support efforts to breed younger age categories and remove geriatric sows from the breeding program, if feasible. Notably, our previously reported clinical data indicate that skeletal growth and maturation in strain 13/N guinea pigs continues through to at least 9 months old , and our breeding dataset confirms that the animals are capable of successful natural delivery with first breeding up to 9 months, one month beyond the 8 months of age typically recommended for guinea pigs, especially when closely monitored by veterinary staff and undergoing radiographic evaluation of the pubic symphysis, as well as subsequent close monitoring, throughout gestation, of symphysis relaxation prior to parturition. We did not find a significant difference in any outcome measure associated with the number of pregnancies, in contrast to results reported in mice, indicating that litter size increases with subsequent pregnancies until plateauing and eventually declining . However, as the decline in mice is not evident until birthing more than five litters, with most substantial effects seen after ten litters, it is possible that the changes previously observed may not have been captured in our dataset, given that the total number litters in our study population did not exceed five. Pairing strategies can have effects on the characteristics of rodent litters. We found no significant differences between the two breeding strategies, regarding the timing of pairing and separation. As breeding success does not appear to be dependent on pairing, programs may select strategies that are preferred based on housing and resources, without compromising production outcomes. In our colony, while trio and harem pairing strategies have been employed for mating, generally, sows are separated at the time of delivery, to care for the pups. Interestingly, in mice, harem-raised weanling mice had significantly higher weaning weights than weanlings raised in a pair breeding configuration , suggesting that future efforts may consider maintaining these pairings post-partum, to optimize the health of the pups post-weaning. 5. Conclusions Altogether, these studies provide valuable information regarding the reproductive characteristics of strain 13/N guinea pigs, establishing benchmarks for their litter size, stillbirth rate, and10 day survival rate. Additionally, the identification of important breeding parameters, as described herein, will aid in the propagation and management of these colonies. As strain 13/N guinea pigs are a vital research resource with utility in infectious disease research and the evaluation of medical countermeasures, the knowledge of factors that contribute to improved reproductive success is incredibly valuable and necessary. Acknowledgments We thank members of the Centers for Disease Control and Prevention's Comparative Medicine Branch for providing care for the animals. Author Contributions Conceptualization, S.C.G. and J.R.S.; methodology, S.C.G., T.F. and J.R.S.; formal analysis, T.F.; investigation, S.C.G., J.D.C.-M. and J.R.S.; resources, C.T.; data curation, S.C.G., T.F., J.D.C.-M. and J.R.S.; writing--original draft preparation, S.C.G., T.F. and J.R.S.; writing--review and editing, T.F., C.T., S.R.W. and J.R.S.; visualization, T.F. and S.R.W.; supervision, C.T. and J.R.S. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The animal study protocols were approved by the CDC Institutional Animal Care and Use Committee (#2465, 30 October 2012; #2711, 22 October 2015; #2958, 23 July 2018; #3193, 21 June 2021). Informed Consent Statement Not applicable. Data Availability Statement Data available upon request. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Overview of strain 13/N guinea pig colony, showing the parental breeding age and litter size. (a) Kernel Density Estimation for Age at Delivery for sows (n = 266) and boars (n = 260). (b) Distribution of number of fetuses in the dataset, from pregnancies yielding viable pups (n = 267). Figure 2 Kernel density estimation of guinea pig strain 13/N sow weight, by age at delivery and age group, as represented in the dataset. Sow weights followed a normal distribution with flatter curves, as expected, for juvenile (0 through 150 d, n = 19) and geriatric populations (older than 900 d, n = 7) due to the lower number of animals in those age categories relative to adults (151 through 900 d, n = 147). animals-13-00895-t001_Table 1 Table 1 Total fetus count and 10 day survival rate in strain 13/N guinea pig pregnancies by sow and boar age at delivery. Total Fetus Count 10 Day Survival Rate Age Category n # of Preg Average SD Average SD Sows Juvenile 19 19 2.2 0.85 0.86 0.32 Adult 147 240 3.3 1.08 0.71 0.35 Geriatric 7 7 1.9 0.90 0.43 0.53 Boars Juvenile 7 7 2.6 1.62 0.79 0.39 Adult 84 243 3.2 1.08 0.72 0.35 Geriatric 6 10 2.4 1.07 0.45 0.50 n, indicates the number of individual sows and boars in each age category for the corresponding number of pregnancies; SD, standard deviation. animals-13-00895-t002_Table 2 Table 2 Percentage of females in strain 13/N guinea pig litters by sow and boar age at delivery. Litter sex ratio was analyzed for a subset of the total pregnancies listed in Table 1. Both litter sex ratio data and sow age were known for 231 of 266 pregnancies, and litter sex ratio and boar age were known for 226 of 260 pregnancies. Percentage Female Age Category n # of Preg Average SD Sows Juvenile 17 17 0.70 0.30 Adult 138 211 0.48 0.35 Geriatric 3 3 0.56 0.51 Boars Juvenile 6 6 0.81 0.22 Adult 82 215 0.50 0.35 Geriatric 5 5 0.18 0.29 n, indicates number of individual sows and boars in each age category for the corresponding number of pregnancies; SD, standard deviation. animals-13-00895-t003_Table 3 Table 3 Analysis of effect of strain 13/N guinea pig sow age at delivery on breeding outcomes. ANOVA was used to analyze differences in mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days for juvenile or geriatric guinea pigs, as compared to adult guinea pigs (t-Stat and p-value set as intercept). Age is based on the age of the parental sow at pup delivery. Sow Variable n Estimate Error t-Stat p-Value Total Fetus Count Sow--Adult 240 3.28 - - - Sow--Juvenile 19 -1.07 0.25 -4.22 0.000033 * Sow--Geriatric 7 -1.43 0.41 -3.49 0.000566 * Percentage Female Sow--Adult 211 0.47 - - - Sow--Juvenile 17 +0.22 0.09 2.45 0.014912 * Sow--Geriatric 3 +0.08 0.21 0.38 0.705116 10 Day Survival Rate Sow--Adult 240 0.71 - - - Sow--Juvenile 19 +0.15 0.08 1.73 0.084573 Sow--Geriatric 7 -0.28 0.14 -2.08 0.038716 * *, indicates values significant at p < 0.05; -, not applicable; estimate, the difference in the average for the respective group compared to adults; error, standard error of the corresponding estimator; t-Stat, t-statistic. animals-13-00895-t004_Table 4 Table 4 Analysis of the effects of strain 13/N guinea pig boar age at delivery on breeding outcomes. ANOVA was used to analyze differences in mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days for juvenile or geriatric guinea pigs as compared to adult guinea pigs. Age is based on the age of the parental boar at pup delivery. Boar Variable n Estimate Error t-Stat p-Value Total Fetus Count Boar--Adult 243 3.24 - - - Boar--Juvenile 7 -0.67 0.42 -1.60 0.111351 * Boar--Geriatric 10 -0.84 0.35 -2.38 0.017905 * Percentage Female Boar--Adult 215 0.49 - - - Boar--Juvenile 6 +0.32 0.15 2.17 0.030858 * Boar--Geriatric 3 -0.31 0.16 -1.93 0.055482 10 Day Survival Rate Boar--Adult 243 0.72 - - - Boar--Juvenile 7 +0.06 0.14 0.45 0.650622 Boar--Geriatric 10 -0.27 0.12 -2.38 0.018261 * *, indicates values that are significant at p < 0.05; -, not applicable; estimate, the difference in averages for the respective group compared to adults; error, standard error of the corresponding estimator; t-Stat, t-statistic. animals-13-00895-t005_Table 5 Table 5 Final significant factors determined by stepwise regression in strain 13/N guinea pig pregnancies, represented by sow and boar age at delivery. Variable Estimate Error t-Stat p-Value Total Fetus Count Sow--Juvenile -0.98 0.28 -3.55 0.00045 * Sow--Geriatric -1.38 0.58 -2.38 0.01783 * Percentage Female Boar--Juvenile 0.32 0.15 2.21 0.0283 * 10 Day Survival Rate Boar--Geriatric -0.28 0.11 -2.40 0.0173 * *, indicates values significant at p < 0.05; estimate, the difference in average for respective group compared to adults; error, standard error of the corresponding estimator; t-Stat, t-statistic. animals-13-00895-t006_Table 6 Table 6 The impact of the number of pregnancies of strain 13/N guinea pig sows on total fetus count, percentage of females in a litter, and survival rate after 10 days, as compared to first pregnancies. Birth Count Preg # # of Preg Average SD t-Stat p-Value 1 157 3.18 1.08 - - 2 71 3.15 1.21 -0.15 0.884566 3 26 3.15 1.29 -0.10 0.918277 4 9 3.22 0.67 0.11 0.909614 5 3 3.00 1.00 -0.27 0.786132 Percentage Female Preg # # of Preg Average SD t -Stat p -Value 1 157 0.48 0.34 - - 2 71 0.50 0.37 0.41 0.682959 3 26 0.63 0.40 1.84 0.066368 4 9 0.37 0.36 -0.77 0.440866 5 3 0.33 0.58 -0.68 0.494708 10 Day Survival Rate Preg # # of Preg Average SD t -Stat p -Value 1 157 0.73 0.34 - - 2 71 0.68 0.38 -0.97 0.333474 3 26 0.74 0.38 0.11 0.913439 4 9 0.59 0.44 -1.13 0.259265 5 3 0.75 0.43 0.08 0.934618 -, not applicable; SD, standard deviation; t-Stat, t-statistic. animals-13-00895-t007_Table 7 Table 7 Analysis of strain 13/N guinea pig breeding outcomes based on the separation of pairs following the breeding period. Breeding couples that were not separated (continuously paired) were compared to those separated prior to breeding (new pairing). Variable n Estimate Error t-Stat p-Value Total Fetus Count Separated 45 3.19 - - - Not Separated 201 0.09 0.18 0.52 0.604819 Percentage Female Separated 41 0.49 - - - Not Separated 174 -0.01 0.06 -0.23 0.817538 10 Day Survival Rate Separated 45 0.67 - - - Not Separated 201 0.11 0.06 1.90 0.058754 -, not applicable; n, number of pairing type for indicated analysis; estimate, the average difference for Not Separated compared to Separated pairings; error, standard error of the corresponding estimator; t-Stat, t-statistic. animals-13-00895-t008_Table 8 Table 8 Analysis of the effect of strain 13/N guinea pig pairing approaches on breeding outcomes. Trio (one male, two females) and quad (one male, three females) pairing approaches were compared to pairs (one male, one female). Birth Interval Variable n Estimate Error t-Stat p-Value Pair 94 82.78 - - - Trio 108 1.19 2.20 0.54 0.587681 Quad 13 7.68 4.50 1.71 0.089348 Total Fetus Count Variable n Estimate Error t -Stat p -Value Pair 112 3.19 - - - Trio 105 0.04 0.15 0.27 0.787221 Quad 19 0.13 0.28 0.46 0.644419 Percentage Female Variable n Estimate Error t -Stat p -Value Pair 96 0.51 - - - Trio 91 -0.04 0.05 -0.76 0.44849 Quad 18 -0.02 0.09 -0.26 0.796354 10 Day Survival Rate Variable n Estimate Error t -Stat p -value Pair 112 0.72 - - - Trio 105 -0.02 0.05 -0.44 0.661492 Quad 19 -0.02 0.09 -0.21 0.831265 -, not applicable; n, number of pairing events for indicated type; estimate, average difference for Trio or Quad, compared to the Pair, breeding strategies; error, standard error of the corresponding estimator; t-Stat, t-statistic. 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PMC10000241 | In North America, the nutrient requirements of dairy cattle are predicted using the Cornell Net Carbohydrate and Protein System (CNCPS) or the National Research Council (NRC). As Holstein is the most predominant dairy cattle breed, these models were developed based on the phenotypic, physiological, and genetic characteristics of this breed. However, these models may not be appropriate to predict the nutrient requirements of other breeds, such as Ayrshire, that are phenotypically and genetically different from Holstein. The objective of this study was to evaluate the effects of increasing the metabolizable protein (MP) supply using CNCPS on milk performance, ruminal fermentation, apparent total-tract digestibility, energy and N utilization, and enteric methane production in Ayrshire vs. Holstein lactating dairy cows. Eighteen (nine Ayrshire; nine Holstein) lactating cows were used in a replicated 3 x 3 Latin square design (35-d periods) and fed diets formulated to meet 85%, 100%, or 115% of MP daily requirement. Except for milk production, no breed x MP supply interaction was observed for the response variables. Dry matter intake (DMI) and the yields of energy-corrected milk (ECM), fat, and protein were less (p < 0.01) in Ayrshire vs. Holstein cows. However, feed efficiency and N use efficiency for milk production did not differ between the two breeds, averaging 1.75 kg ECM/kg DMI and 33.7 g milk N/100 g N intake, respectively. Methane yield and intensity and urinary N also did not differ between the two breeds, averaging 18.8 g CH4 /kg DMI, 10.8 g CH4 /kg ECM, and 27.6 g N/100 g N intake, respectively. Yields of ECM and milk protein increased (p <= 0.01) with increasing MP supply from 85% to 100% but no or small increases occurred when MP supply increased from 100 to 115%. Feed efficiency increased linearly with an increasing MP supply. Nitrogen use efficiency (g N milk/100g N intake) decreased linearly (by up to 5.4 percentage units, (p < 0.01) whereas urinary N excretion (g/d or g/100 g N intake) increased linearly (p < 0.01) with an increasing MP supply. Methane yield and emission intensity were not affected by MP supply. This study shows that feed efficiency, N use efficiency, CH4 (yield and intensity), and urinary N losses did not differ between Ayrshire and Holstein cows. Energy-corrected milk yield and feed efficiency increased, but N use efficiency decreased and urinary N losses increased with increasing dietary MP supply regardless of breed. Ayrshire and Holstein breeds responded similarly to increasing MP levels in the diet. metabolizable protein Ayrshire Holstein milk production enteric methane N efficiency Agriculture and Agri-Food Canada (Ottawa, ON, Canada)Agrinova (Alma, QC, Canada)J-002372 This research (Project # J-002372) was funded by Agriculture and Agri-Food Canada (Ottawa, ON, Canada) and Agrinova (Alma, QC, Canada). pmc1. Introduction Ayrshire cows represent 1.5% and 0.3% of the dairy cow population in Canada and USA , respectively, as the overwhelming majority (i.e., 94%) of dairy cows are Holstein. Ayrshire is a smaller breed than Holstein (600 vs. 700 kg mature body weight [BW]) with lower milk production, but higher milk fat and milk protein concentrations, averaging 25.0 vs. 33.5 kg/d, 4.09 vs. 3.96 %, and 3.39 vs. 3.27%, respectively . Ayrshire cows are known for the good quality of the udder, which may help in reducing the incidence of mastitis and lower milk somatic cell count (SCC). In addition, they are subject to less leg and feet problems, and are highly adaptable to various management systems and to harsh conditions . In addition, the replacement rate of Ayrshire cows is lower than other dairy cattle populations in Canada (38 vs. 41%, ), which represents an advantage over other breeds such as Holstein. Distinctive phenotypic and genetic characteristics of Ayrshire cows may thus result in different nutritional requirements compared with Holstein cows. The nutritional requirements of Ayrshire cows are not well defined, as limited research has been conducted on their nutrient requirements. As Holstein is the most predominant dairy cattle breed, the phenotypic, physiological, and genetic characteristics of Holsteins have been used to develop ration formulation programs. However, other breeds (such as Ayrshire) may have different digestive physiology and ruminal microbial diversity, affecting their nutrient requirements and capacity to digest feeds. For instance, a number of studies have indicated significant variation between Holstein and Jersey cows in gastro-intestinal tract size, the passage rate of digesta, the type and abundance of ruminal microbes, and the concentration and pattern of volatile fatty acid (VFA) . Welch et al. reported variation between cattle breeds in rumination time. Rodriguez et al. and Olijhoek et al. reported higher concentrations of ruminal fermentation end-products (total VFA and ammonia [NH3]) and greater organic matter (OM), neutral detergent fiber (NDF), and starch digestibility in Jersey compared with Holstein cows fed the same diet, suggesting higher microbial activity and digestive capacity in the gastro-intestinal tracts of Jersey cows. Beecher et al. reported bigger reticulo-rumen and omasum per unit of BW in Jersey cows compared with Holstein cows and variation in ruminal microbial populations between the two breeds. These differences may lead to variations in voluntary DMI potential, the ability to digest fiber, and energy and protein (i.e., MP) requirements for milk production. For instance, Rodriguez et al. reported different responses to dietary rumen undegradable protein (RUP) levels between Holstein and Jersey cows. Such differences may as well exist between Ayrshire and Holstein cows. To the best of our knowledge, very few studies have been conducted to determine differences between Ayrshire and Holstein cows in terms of their energy and N metabolism . Nitrogen metabolism in the rumen and the ability to convert rumen degradable protein (RDP) to microbial crude protein is largely influenced by DMI, the degradation rate of feed in the rumen, the rate of passage through the gastro-intestinal tract, and the function of ruminal microorganisms . Protein requirement can be defined as the amount of MP supply required to maximize milk yield. It could be also defined as the amount of RDP supply required to maximize microbial protein synthesis and fiber digestibility. Dairy cows require a given amount of amino acids (AA) absorbed at the intestinal level to meet their protein requirements (i.e., MP) for maintenance, pregnancy, and targeted levels of milk production . Rations are formulated to provide minimal RDP to optimize fiber digestion and to maximize microbial protein synthesis , which is estimated to provide 52-63% of MP requirements of high producing cows . Sources of RUP are then added in the diet to meet the estimated MP requirement at 100%. Currently, ration formulation for Ayrshire dairy cows is performed using models based on the nutrient requirements for the Holstein breed and by taking into account differences in BW, predicted DMI, milk production, and milk composition. When the MP supply is inadequate, milk production decreases and the genetic potential of dairy cows to produce milk is not achieved. On the other hand, when the MP supply is above the requirement, N milk efficiency declines and urinary N excretion increases, which adversely affect the environmental footprint of milk production . One of these two scenarios is likely to occur when the MP requirements of minor breeds of dairy cows, such as Ayrshire, are not well defined. In the present study, we hypothesized that given the differences in phenotypic and the genetic characteristics of Ayrshire versus Holstein cows, the MP requirements of Ayrshire cows to optimize milk production and feed efficiency may differ from that of Holstein cows, and that ration formulation using diet models [e.g., Cornell Net Carbohydrate and Protein System (CNCPS; version 6.55)] would not accurately predict the MP requirements of the Ayrshire breed. The environmental footprint of milk production also encompasses enteric CH4 emissions. Potential variation between Ayrshire and Holstein cows in DMI (due to differences in BW), milk production, ruminal microbial populations, and VFA pattern can influence CH4 emission yield (g/kg DMI) and intensity (g/kg ECM). To our knowledge, studies on enteric CH4 emissions from Ayrshire cows are scarce and none of the existing studies compared emissions from Ayrshire cows versus Holstein cows. We hypothesized that differences between the two breeds in the size of the gastro-intestinal tract, ingestion capacity, and ruminal feed degradation (rate, passage) may result in different CH4 emissions. Thus, the objective of this study was to investigate the effect of dietary MP supply on the milk production, milk composition, nutrient utilization, ruminal fermentation characteristics, apparent total-tract digestibility, and enteric CH4 production of Ayrshire and Holstein dairy cows. 2. Materials and Methods This study was conducted at the Sherbrooke Research and Development Centre, (Sherbrooke, QC, Canada). Animal procedures were conducted under the approval of the local Institutional Animal Care Committee (number 566) and in accordance with the guidelines of the Canadian Council on Animal Care . 2.1. Cows, Experimental Design, and Diets Eighteen (9 Ayrshire; 9 Holstein) multiparous lactating cows, of which 6 of each breed were ruminally cannulated (10 cm, Bar Diamond Inc., Parma, ID, USA), were used in a replicated 3 x 3 Latin square design (35-d periods). The 2 breeds were offered diets balanced to supply 85%, 100%, or 115% of the daily MP requirement. Experimental diets (Table 1) were formulated using the CNCPS model (version 6.55). Prior the start of the experiment, Holstein and Ayrshire cows were kept in tie-stall and fed (ad-libitum) diets (pre-experiment diets) as a total mixed ration formulated (CNCPS, version 6.55) to meet net energy of lactation (NEL) and their MP requirements (i.e., 100% supply). Differences in BW, DMI, milk production, and milk composition between Ayrshire and Holstein cows required balancing breed-specific diets to meet their nutrient requirements. When fed the pre-experiment diets, the Holstein cows averaged (mean +- SD) 26.0 +- 2.34 kg/d DMI, 46.3 +- 4.5 kg/d milk, 3.96 +- 0.38% milk fat, and 2.97 +- 0.14% milk protein. The Ayrshire cows averaged 21.6 +- 1.58 kg/d DMI, 35.7 +- 3.4 kg/d milk, 4.18 +- 0.35% milk fat, and 3.28 +- 0.16% milk protein. In terms of absolute values (i.e., amount of MP supplied), the diets supplied 2710 and 2429 g/d of MP for Holstein and Ayrshire cows, respectively. Based on these data and the characteristics of the cows at the start of the trial (Holstein: 92 +- 22 days in milk (DIM), 701 +- 55.8 kg BW; Ayrshire: 99 +- 16 DIM; 566 +- 48.5 kg BW), experimental diets were balanced to supply 85%, 100%, or 115% of the daily MP requirement (Table 1). During the experiment, cows were housed in individual tie-stalls and had free access to water. The diets were delivered in equal meals twice daily (0930 and 2130 h). One Holstein cow was diagnosed with severe foot lesions causing lameness and was eliminated from the experiment. The experimental diets were offered to cows to be fed ad libitum (5% orts, on an as-fed basis) as a total mixed ration with forage:concentrate ratio (on a DM basis) of 67:33 for Holstein cows and 62:38 for Ayrshire cows. For each breed, dietary forage proportions (i.e., corn silage; alfalfa silage; timothy hay) were maintained constant across MP supply levels. Increasing MP supply from 85% to 100% of the requirements was achieved by decreasing urea, corn grain, and soybean hulls proportions while increasing soybean meal, heat-treated soybean meal, and corn gluten meal proportions. Increasing MP supply from 100% to 115% was achieved by decreasing corn grain, soybean hulls, and soybean meal proportions, while increasing heat-treated soybean meal and corn gluten meal proportions. Ingredient and chemical composition of the experimental diets are detailed in Table 1. Feed intake, milk production, milk composition, and BW were determined for 18 cows (i.e., 6 Latin squares) whereas the 12 ruminally cannulated cows (i.e., 4 Latin squares) were used for measurement of enteric CH4 production, ruminal fermentation characteristics, apparent total-tract digestibility, and N excretion. The availability of only 2 chambers (1 cow/chamber) to determine enteric CH4 production of 12 cows (3 cows/Latin square) necessitated staggering the Latin squares by 5 d and CH4 production measurements by 5 d. For each Latin square, the 35-d (including 5 d of staggering) were organized as follows: adaptation to dietary treatments from d 1 to d 14; CH4 production from d 15 to d 23; ruminal fluid sampling from d 25 to d 26; feed intake, milk production, milk composition, apparent total-tract digestibility and N excretion from d 27 to d 33; and BW on d 34 and d 35. 2.2. Apparent Total-Tract Digestibility, N Excretion, and BW Intake, apparent total-tract digestibility, and N excretion were measured as described by Benchaar . Feed consumption was recorded daily by weighing feeds offered to and refused by the cows. Samples of the experimental diets, feed ingredients, refusals, and feces were collected daily and stored at -20 degC. These samples were later thawed, composited by cow within period, freeze-dried, ground to pass a 1-mm screen using a Wiley mill (standard model 4; Arthur M. Thomas, Philadelphia, PA, USA) and analyzed for DM, OM, total N, neutral detergent fiber (NDF), acid detergent fiber (ADF), starch, and gross energy (GE). Total collection of feces and urine was performed as described by Benchaar by fitting cows with harnesses and tubes allowing the collection of feces and urine separately. A representative (2%) sample of thoroughly mixed feces was collected daily. Urine was collected in containers containing appropriate amounts of H2SO4 to keep pH < 2.0. A representative urine sample (2%) was collected and kept frozen at -20 degC until analyzed for total N and purine derivatives (allantoin and uric acid). Cows were weighed at the beginning and the end of each experimental period on 2 consecutive days before the a.m. feeding and after the a.m. milking. 2.3. Ruminal Fermentation Characteristics and Protozoa Enumeration Ruminal fluid was collected from each cow before (0 h) and 1, 2, 4, 6, and 8 h after the a.m. meal over 2 days as described in Benchaar et al. . A total of 250 mL was collected from several locations (i.e., anterior dorsal, anterior ventral, medium ventral, posterior dorsal, and posterior ventral) within the rumen using a 50-mL syringe attached to a stainless tube ending with a probe covered by a fine metal mesh (RT Rumen Fluid Collection Tube, Bar Diamond Inc., Parma, ID, USA). Ruminal fluid was subsampled (15 mL) and frozen immediately at -20 degC for later determination of VFA concentrations. Additional subsamples (15 mL) were acidified to pH 2 with 50% sulfuric acid and frozen at -20 degC for later determination of NH3 concentrations. Protozoa were counted from ruminal content collected before (0 h) and 4 h after the a.m. feeding as described in Benchaar et al. . Ruminal content (approximately 1 L) was squeezed through 4 layers of cheesecloth and a 5-mL portion of the squeezed ruminal fluid was preserved using 5 mL of methyl green formalin-saline solution for protozoa enumeration . Protozoa samples were stored at room temperature in darkness until counting. Protozoa were microscopically enumerated using a counting chamber (Neubauer Improved Bright-Line counting cell, 0.1 mm depth; Hausser Sc0.82ientific, Horshamm, PA, USA). Ruminal pH was measured continuously on 12 cows for 48 h using the LRCpH bolus system (DASCOR Inc., Oceanside, CA, USA) initially described in Penner et al. . The system consisted of a battery-powered LRCpH data logger connected to LRpH sensors with ceramic frit, enveloped by polyvinyl chlorine case. The sensors were calibrated to pH 4.00 and 7.00 at 39 degC prior to utilization. The probes were attached to 1.5-kg metal weights to ensure that they were always immersed in the ruminal fluid and then placed in the ventral sac of the rumen of each cow. Ruminal pH was recorded every 2 min. After 48 h, the probes were removed and data were downloaded. The probes were then immersed in pH 4.00 and pH 7.00 buffers kept at 39 degC, and the probes measurement drifted positively at an average of 2.03 +- 1.30%. Data were processed with DASCOR LRCpH software V-6.1.0. and were corrected for drift using a linear equation of the initial and final standard measurements from each cow/period. The pH data were summarized as mean pH, minimum pH, maximum pH, time spent below pH 6.0, time spent below pH 5.6, and time spent below pH 5.2 . 2.4. Milk Production and Milk Composition Cows were milked in their stalls twice daily at 7:00 and 19:00, and milk production was recorded at each milking. The data recorded during the 7 d of apparent total-tract digestibility measurement were used for the statistical analysis. During that period, milk samples were taken from each cow at each milking, stored at 4 degC with a preservative (2-bromo-2-nitropropan-1,3-diol), and sent to a commercial laboratory (Lactanet, Sainte-Anne-de-Bellevue, QC, Canada) for analysis of fat, protein, true protein, lactose, total solids, milk urea nitrogen (MUN) and SCC. 2.5. Enteric Methane Production The respiration chambers measured 4.09 m long x 2.95 m wide x 2.84 m high. When chamber doors were closed, air entered the chamber through a ventilation duct and exited through an exhaust duct. Air temperature inside the chambers was maintained at 16.8 +- 0.16 degC. Air flow into and out of the chambers was measured using inline mass flowmeters (FT2; Fox Thermal Instruments Inc., Marina, CA, USA) and was maintained at 180 +- 10 m3/h. Methane concentration was continuously measured at the air entrance and exhaust ducts using CH4 analyzers (SERVOPRO 4100; Servomex, Brighton, East Sussex, UK). The amount of CH4 (entering and leaving the chamber) was calculated by multiplying the concentration of CH4 by the airflow (at entrance and exhaust ducts). The difference between the incoming and outgoing mass of CH4 corresponded to the amount of enteric CH4 emitted in each chamber by the animal. The chambers were calibrated at the beginning of each experimental period by releasing known amounts of CH4 in each chamber (with no cow inside). The calibration factors (i.e., to adjust each chamber to 100% recovery) specific to each experimental period were used to correct CH4 emissions data. A small positive pressure was generated inside each chamber to prevent inflow of gases into the chambers. Methane was recorded every minute over 5 consecutive days and fluxes were averaged to derive 24-h CH4 emissions. Cows were preconditioned to the environmental chambers before the beginning of the experiment. To reduce the effect of isolation on animal behavior, the chambers were equipped with windows and speakers so the cow in the chamber could see and hear other cows. Cows entered the chambers 18 h before starting CH4 measurements. Within each chamber, the cow was kept in a tie stall measuring 1.82 m long x 1.60 m wide that was elevated 25 cm above the floor. Manure was collected from each cow in a stainless box placed below and to the rear of each stall. To feed and milk the cows and remove the manure, farm personnel accessed the chambers twice daily and the doors were kept opened for 1 to 1.5 min to allow exchange of material in and out of the chambers. This resulted in interruptions of flux measurements for 15 to 30 min, which is the time required for gas concentrations to reach steady state. Missing concentrations of CH4 during these interruptions were estimated as the average of the CH4 concentration immediately before the interruption and immediately after gas concentration reached steady state. These interruptions had little effect on daily emissions because fluxes were calculated every minute and used to derive the 24-h period emissions values. Cows in the chambers were milked twice daily, had free access to water, and were fed for ad libitum intake (5% orts on an as-fed basis). Offered feed and orts were weighed daily to determine feed consumption. Samples of offered feed and orts were collected, pooled across days, and kept frozen for later determination of DM and GE concentrations. 2.6. Chemical Analyses Dry matter content was determined by drying samples in a vacuum oven at 100 degC overnight (method 934.01; ). Ash content was determined by sample incineration at 550 degC overnight in a muffle furnace (method 942.05; ). Organic matter content was calculated as the difference between 100 and the percentage of ash. Crude protein (N x 6.25) was determined using a LECO N analyzer (TruMac N determinator, LECO Corporation, St. Joseph, MI, USA) according to AOAC (method 990.03). The concentration of NDF was determined as described by Van Soest et al. with the use of sodium sulfite and the inclusion of heat stable a-amylase. The ADF content was determined according to AOAC (method 973.18). The procedures for NDF and ADF were adapted for use in an Ankom 200 Fiber Analyzer (Ankom Technology Corp., Fairport, NY, USA). The concentration of starch was determined colorimetrically according to AOAC (method 996.11). Energy concentration in diet, feces, urine, and milk samples was determined using an oxygen bomb calorimeter (model 6200, Parr Instrument Company, Moline, IL, USA). The concentration of N in acidified urine samples was determined by micro-Kjeldahl analysis . Purine derivatives (allantoin and uric acid) in urine were analyzed according to the procedure of George et al. using HPLC (model 210, Varian ProStar, Agilent Technologies Canada Inc., Montreal, QC, Canada). Analysis of VFA was performed using a gas chromatography (GC) equipped with a flame ionization detector and auto-injector (6850 network GC system, Agilent Technologies, Mississauga, ON, Canada) fitted with a DB-FFAP column (30 m x 0.250 mm x 0.25 mm; Agilent Technologies, Mississauga, ON, Canada). Ammonia concentration was determined as in Weatherburn . Total protein, true protein, fat, lactose, total solids, MUN, and SCC in milk samples were analyzed by infrared spectroscopy (MilkoScan FT 6000; Foss Electric, Hillerod, Denmark). Milk composition was adjusted taking into account differences in milk yield between a.m. and p.m. milkings. 2.7. Statistical Analyses Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC, USA) and the statistical model included breed, MP supply, interaction of breed x MP supply, and period as fixed effects and cow within breed as random effect. Concentrations of VFA and NH3, and protozoa density data, were analyzed as repeated measures using the same model with the addition of the fixed effects of day, sampling time (i.e., hour) and all interactions. The CH4 data were also analyzed as repeated measures with the inclusion of the fixed effects of day and interaction of day with study factors. The appropriate covariance structure used for repeated-measures analyses was chosen according to the type of repeated measurement (single or double), sampling interval (equal or unequal) and to achieve the lowest Akaike, corrected Akaike, and Bayesian information criteria values. Therefore, the choice of covariance structure varied with the response variable. The covariance structure used cow within treatment x period as subject of the repeated measures. Orthogonal polynomial contrasts (linear and quadratic) were used to examine MP supply effect on response variables. Differences between treatments (i.e., main effects: breed and MP supply) and their interactions (i.e., Breed x MP supply) were declared significant at p <= 0.05 and tendencies for 0.05 < p <= 0.10. Data are reported as least square means with standard error of the means (SEM). 3. Results 3.1. Milk Production and Milk Composition Data of DMI, milk production, milk composition, and feed or N efficiency are presented in Table 2. The interaction of breed x dietary MP supply was significant (p = 0.05) only for milk yield. The milk yield of Ayrshire cows increased linearly as the dietary MP level increased whereas a quadratic increase was observed for Holstein cows (i.e., no further increase from 100% to 115% MP supply). Overall, Ayrshire cows produced 25% less (p < 0.01) milk than Holstein cows (32.8 vs. 43.7 kg/d). Concentrations of fat, protein, and total solids were 0.3, 0.3, and 0.5 percentage units greater (p <= 0.06) in the milk of Ayrshire cows than in the milk of Holstein cows. Milk lactose concentration averaged 4.66% and was not affected by breed. Ayrshire cows produced (kg/d) less (p < 0.01) milk fat (-19%) and milk protein (-16%) than Holstein cows. Consequently, yield ECM was less (p < 0.01) for Ayrshire cows compared with Holstein cows (36.0 kg/d vs. 45.3 kg/d, respectively). Concentrations of MUN tended to be less (p = 0.07) for Ayrshire cows compared with Holstein cows (8.78 vs. 9.90 mg/dL). The intake of DM was 20% less for Ayrshire cows than for Holstein cows, but did not differ between the two breeds when expressed as a percentage of BW (average 3.66%). Feed efficiency expressed as kg of milk/kg of DMI tended (p = 0.10) to be less for Ayrshire cows compared with Holstein cows (1.60 vs. 1.69 g milk/kg DMI), but did not differ between the two breeds, if expressed on an ECM yield basis. Likewise, N use efficiency (g N in milk/100 g of N intake) was not different between Ayrshire cows and Holstein cows. Milk protein concentration increased (p = 0.02) with increasing MP supply from 85% to 100% but no further increase was observed when MP supply increased from 100% to 115% (i.e., quadratic response). However, concentrations of fat, lactose, and total solids were not affected by MP supply. Consequently, the yield (kg/d) of milk protein increased (p <= 0.01) in a quadratic manner (i.e., no additional increase from 100% to 115% MP supply. The yields of fat and lactose increased linearly (p < 0.01) with increasing MP supply, with a quadratic tendency for milk lactose (p = 0.10). The yield of ECM increased linearly (p < 0.01) as MP supply increased, but with a quadratic tendency (p = 0.07). Increasing MP supply was associated with a numerical increase (p = 0.12) in DMI (kg/d) but had no effect on DMI expressed on a BW basis. A linear increase (p < 0.01) was observed for feed efficiency (kg ECM/kg DMI) as dietary MP supply increased. However, N use efficiency decreased linearly (p < 0.01) with increasing MP supply. 3.2. Ruminal Fermentation Characteristics Data of continuous measurements of ruminal pH are presented in Table 3. A tendency (p = 0.07) for breed x MP supply interaction was observed for the mean daily ruminal pH: pH declined linearly in Ayrshire cows as MP supply increased but was not affected in Holstein cows. Regardless of breed and dietary MP supply, the minimum and maximum ruminal pH averaged 5.78 and 6.81, respectively. Daily time spent at pH < 6.0 averaged 205 min/d whereas time spent at pH < 5.6 was negligible and averaged 8 min/d. Because interactions between breed, dietary MP supply, measurement day, and sampling time were not significant for VFA, NH3, and protozoa, only averages of the 2 d measurements and the sampling times are reported (Table 4). No effects of breed or MP supply were observed for total VFA concentration, the molar proportions of individual VFA, the acetate:propionate ratio, or NH3 concentration. Protozoa density was less in Ayrshire cows than in Holstein cows (4.4 x 105 vs. 6.3 x 105/mL) and was unaffected by dietary MP supply. 3.3. Apparent Total-Tract Digestibility The effects of breed, dietary MP supply, and their interaction on apparent total-tract digestibility are presented in Table 5. The apparent total-tract digestibility of DM, OM, crude protein (CP), NDF, and GE was greater (p <= 0.05) in Ayrshire cows than in Holstein cows. Starch digestibility averaged 98% and was not affected by breed. A tendency for a linear increase (0.5 < p <= 0.10) in the digestibility of OM and GE was observed as dietary MP supply increased, mainly related to increased (p <= 0.04) CP and starch digestibility. However, the apparent total-tract digestibility of DM, NDF, or ADF was not affected by dietary MP supply. 3.4. Methane Production Interactions between breed, dietary MP level, and measurement days were not significant for CH4 data, and therefore, only averages across measurement days are presented in Table 6. Similar to the response observed during the 7-d collection period, DMI was 22% less (p < 0.01) for Ayrshire cows than for Holstein cows and increased linearly (p = 0.01) with increasing MP supply. Daily CH4 emissions were 20% less (p = 0.06) for Ayrshire cows compared with Holstein cows (386 vs. 484 g/d) and increased linearly (p = 0.03) as the MP supply increased. However, there was no effect of breed or MP supply on CH4 yield (averaging 18.9 g/kg DMI) or CH4 intensity (averaging 10.8 g/kg ECM). 3.5. Energy Utilization Data of energy intake, expenditure, and partitioning are presented in Table 7. Compared with Holsteins cows, the intakes of gross, digestible, metabolizable, or net energy were less (by 21, 18, 18, and 18%, respectively; p = 0.01) for Ayrshire cows than for Holstein cows. There was no effect of dietary MP supply on energy intake variables. Daily fecal, urinary, CH4, and milk energy expenditures (Mcal/d) were less (p <= 0.06) for Ayrshire cows than for Holstein cows (-26%, -18%, -20%, and -21%, respectively). However, when expressed as a percentage of GE intake, energy expenditures in urine, CH4, and milk were not affected by breed. Only fecal energy loss was less in Ayrshire cows than in Holstein cows (30.0% vs. 32.3%, p = 0.02). Increasing the dietary MP supply linearly (p <= 0.03) increased the daily energy expenditure in urine, CH4, and milk, but had no effect on the daily energy expenditure in feces. When expressed as a percentage of GE intake, urine and milk energy expenditures increased linearly (p <= 0.04) when the dietary MP supply increased. Energy expenditure in CH4 was unaffected whereas fecal energy expenditure tended (p = 0.09) to linearly decrease with increasing MP supply. The maintenance energy expressed as a percentage of GE intake was not affected by breed or MP supply. The proportion of metabolizable energy (ME) used for milk energy averaged 42.7% and was unaffected by breed, but tended (p = 0.10) to increase linearly with increasing MP supply. 3.6. Nitrogen Utilization Data of N intake and excretion are presented in Table 8. The less N intake for Ayrshire cows resulted in reduced (p <= 0.02) daily N excretion (feces, urine, and total) compared with Holstein cows. When expressed as a percentage of N intake, urinary N excretion was not affected by breed. In contrast, fecal N and total N excretions relative to N intake were less (p = 0.01) for Ayrshire cows than for Holstein cows. The daily urine excretion of allantoin and uric acid was less (p <= 0.01) in Ayrshire than Holstein cows. The daily N intake and total (urine, total) N excretion increased linearly (p < 0.01) whereas fecal N excretion tended (p = 0.08) to increase as the MP supply increased. The increase in the amount of N daily excreted in urine was of a greater magnitude for Holstein cows than for Ayrshire cows, explaining the tendency (p = 0.07) of the interaction of breed x MP supply. When expressed as a percentage of N intake, fecal N excretion decreased linearly (p < 0.01) whereas urinary N and total N excretion increased linearly (p <= 0.01) with increasing MP supply. The daily urine excretion of purine derivatives (mmol/d) were not affected by an increasing MP supply. 4. Discussion Different nutritional models are available for dairy cow diet formulation. In our study, the CNCPS model (version 6.5/6.55) was used. This model is widely used to formulate diets of dairy cattle with an updated feed library and the version used (6.5/6.55) integrated the most recent findings . Nutrient (e.g., metabolizable MP) requirements are model dependent and the use of other models (e.g., NRC ) may result in different predictions than those from the CNCPS model. Nevertheless, these predictions (i.e., MP supply) are more accurate than CP in estimating the AA availability to the cows. Diets are formulated to meet the nutrient requirements of the dairy cow, particularly energy (ME) and protein (MP) requirements. Such requirements vary according to DMI, milk yield, milk component, BW, stage of lactation (DIM), parity, etc. The goal is to supply adequate amounts of nutrients allowing the cows to express their full genetic potential of production. Because Holstein and Ayrshire cows are breeds that differ in their physical characteristics (e.g., BW, rumen size, potential DMI) and their genetic potential of milk production (i.e., yield and composition), meeting nutrient requirements for milk production requires formulating a diet (e.g., 100% MP) specific to each breed. If fed the same experimental diets as Holstein cows, the Ayrshire cows would have been underfed relative to their requirements and would be in a more responsive "status", which would have totally confounded the interpretation of the results. For instance, the diets formulated to supply 85%, 100%, and 115% of the MP requirement of Holstein cows would meet only 81%, 94%, and 109% of the MP requirement of Ayrshire cows (Table 9), respectively. Thus, feeding diets specific to each breed versus feeding the same diet to both breeds was appropriate to evaluate each breed responses to increasing MP supply (85%, 100%, and 115%). 4.1. Breed x Dietary MP Level Interaction With the exception of milk yield, the two breeds responded similarly to changes in dietary MP supply as shown by the absence of breed x dietary MP supply interaction for almost all the measured variables (see discussion below). In Ayrshire cows, milk yield increased linearly with increasing MP supply whereas a quadratic response was observed in Holstein cows (i.e., no additional increase from 100% to 115% MP supply). This interaction indicates that the MP requirements of the Ayrshire breed for milk production may be greater than those predicted by CNCPS. However, the breed x MP supply interaction was not significant for ECM or milk component yields (p >= 0.16). To our knowledge, this is the first study investigating the responses of Ayrshire vs. Holstein cows to variations in MP supply. 4.2. Effect of Breed From DHI reports in Canada , Ayrshire cows are typically 15% lighter than Holstein cows and produce 25, 23, and 23% less milk, milk fat, and milk protein, respectively, than Holstein cows. These national averages are similar to the differences between breeds observed in the present study, except for milk protein yield (16% less in Ayrshire cows vs. Holstein cows in this study). From DHI data and bulk milk analyses in Pennsylvania, Cerbulis and Farrell reported that Ayrshire cows produced milk with 7% and 10% higher concentrations of milk protein and fat, but only 5% less milk yield than Holstein cows, yielding a 6% greater milk fat yield and a similar milk protein yield. On the other hand, in a quantitative genetic study on cows kept in different sites, McAllister et al. reported that Ayrshire cows produce 29, 31, and 24% less milk, milk protein, and milk fat than Holstein cows. According to Lactanet , concentrations of fat and protein are greater (0.13 and 0.12 more percentage units) in the milk of Ayrshire than in that of Holstein cows. In the present study, where the two breeds were under controlled-experimental conditions, milk fat and milk protein concentrations were also greater for Ayrshire cows than for Holstein cows (0.33 and 0.33 percentage units more, respectively). The evolution of the two breeds throughout the past decades necessitates revising the energy and protein requirements of Ayrshire cows as more attention has been given to defining the nutrient requirements of Holstein cows. Differences in MP requirement between different dairy cattle breeds have been rarely addressed. In lactating dairy cows, intake is primarily driven by ECM yield, followed by BW . When expressed on a BW basis, DMI observed in this study averaged 3.66% (18.3 kg/100 kg metabolic BW, data not shown) and was not affected by breed, suggesting that BW was the main driving factor of DMI. The less DMI (20% lower) observed in Ayrshire cows was mainly due to the lower ECM yield (21% lower) which resulted in no change in feed efficiency (kg ECM/kg DMI) between the two breeds in response to an increasing MP supply. The efficiency of energy use (Mcal milk energy/100 Mcal GEI; Mcal milk energy/100 Mcal ME intake) or N use (g milk N/100 g N intake) were not different between the two breeds despite lower GE, ME, and N intakes (-21%, -18%, and -15%, respectively) in Ayrshire cows compared with Holstein. The greater DM, GE, and CP apparent total-tract digestibility in Ayrshire cows versus Holstein cows are more likely due to the lower forage percentage (4 percentage units) in Ayrshire diets compared with Holstein diets. Alternatively, Ayrshire cows (smaller breed than Holstein) may have a bigger gastro-intestinal tract relative to BW. To our knowledge, there are no reports that compare gastro-intestinal tract size between Ayrshire and Holstein cows. When adjusted to BW, Beecher et al. reported that Jersey cows (smaller than Holstein cows) have a bigger gastro-intestinal tract (143 g/kg BW) than Holstein cows (129 g/kg BW). In this study, at similar potential DMI (as a percentage of BW) and the potentially larger gastro-intestinal tract in Ayrshire cows, the ruminal passage rate may have been slower in Ayrshire cows than in Holstein cows, which may have increased fiber (and consequently OM) digestibility, compared with Holstein cows. An increase in fiber retention time in the rumen (i.e., slower passage rate) is expected to enhance fiber digestibility , which was reflected in the current study by the greater fiber (NDF, ADF) digestibility in Ayrshire cows compared with Holstein cows. When Jersey and Holstein cows were fed similar diets, Aikman et al. and Olijhoek et al. reported higher NDF digestibility in Jersey cows. However, this difference did not translate into improved feed efficiency; energy losses (relative to GEI) in urine, CH4, and N loss in urine were not different between the two breeds. Studies investigating energy and N use efficiencies between breeds are scarce. In agreement with our findings, Dickinson et al. reported no difference in energy efficiency (milk energy/GEI) between Ayrshire and Holstein first parity cows. Likewise, Dong et al. reported no effect of dairy breed (Holstein; Jersey x Holstein; Norwegian x Holstein) on energy partitioning. Kristensen et al. observed no difference in the efficiency of N use between Holstein, Jersey, or other breeds of dairy cattle. Therefore, data from this study and others suggest that Ayrshire cows do not have an advantage over Holstein cows in energy and N use efficiency for milk production. The difference in DMI between the two breeds (5.8 kg/d less for Ayrshire cows) accounts for the fewer (98 g/d) daily enteric CH4 emissions from Ayrshire cows compared with Holstein cows. In contrast, CH4 yield (18.9 g/kg DMI) and intensity (10.8 g/kg ECM) were not affected by breed. The yield and intensity of the CH4 emissions of Ayrshire cows (19.0 g/kg DMI and 12.1 g/kg milk, respectively) are close to the mean values based on a large number of observations for Holstein cows . Other studies reported no differences in CH4 yield and intensity between different breeds of dairy cattle , beef cattle , or even between dairy and beef cattle breeds fed similar diets. The absence of variation in ruminal methanogen populations between breeds may explain such similar enteric CH4 yields. King et al. reported 85% similarity in the methanogen population between Holstein and Jersey breeds. Others also reported similarity in methanogen communities between dairy cattle breeds , beef cattle breeds , or between dairy and beef cattle . The absence of breed effect on ruminal VFA (total concentration and molar proportions) is in line with the lack of breed effect on CH4 yield. In accordance, others reported no effect of breed of dairy cattle or beef cattle on ruminal VFA concentration or pattern. The lower density of protozoa in the ruminal content of Ayrshire cows compared with that of Holstein cows was probably due to less DMI in Ayrshire cows as a positive relationship between DMI and the protozoa population in the rumen, as has been previously reported . In crossbred Charolais and purebred Luing (LU) beef steers with similar DMI, breed had no effect on ruminal protozoa population . 4.3. Effect of MP Supply The CNCPS model was used to formulate diets to meet the MP requirements (100%) of Ayrshire cows and Holstein cows, based on BW, milk production and milk composition, and DIM. When MP supply was reduced to 85% or increased to 115% of the requirement, RDP was kept adequate (>=9.5% DM) to maintain ruminal health . Reducing MP supply to 85% involved decreasing the proportions of ingredients with elevated RUP content (i.e., soybean meal, heat-treated soybean meal, corn gluten meal). In contrast, increasing MP supply to 115% was achieved by increasing dietary proportions of heat-treated soybean meal and corn gluten meal. As a consequence, dietary CP concentration increased with MP supply. The quadratic increase in ECM yield, and the yield and concentration of milk protein with an increased dietary MP supply resulted from the large increase when MP supply increased from 85% to 100%, but a small (or no) increase when MP supply increased further to 115%. Meanwhile, increasing MP supply caused a linear increase in milk fat and milk lactose yields, with quadratic tendencies for milk lactose yield. The observed increase in performance was not associated with increased gross, digestible, metabolizable, or net energy intakes and is therefore solely related to the increased MP supply. Rather, this increase was related to the increase in CP intake and digestibility as dietary MP level increased. The lack of MP supply effect on ruminal NH3 concentration and urinary allantoin and uric acid suggest that microbial protein synthesis was unaffected, probably because of the adequate dietary RDP supply. Therefore, the increase in RUP contribution to MP supply is the main reason for the enhanced performance. In agreement, Broderick reported an increase in milk, fat, and protein yields when dietary RUP (% of DM) increased from 4.83% (CP = 15.1% of DM) to 5.48% (CP = 16.6% of DM). However, no further increases were observed when RUP increased to 6.22% (CP = 18.3% of DM) in that study. Bahrami-Yekdangi et al. reported a quadratic response of milk production to increasing MP supply with RUP increasing from 4.7% to 7.1% of DM: the lowest and the highest milk yield occurred at 4.7% RUP (CP = 15.1% of DM) and 5.5% RUP (CP = 16.4% of DM), respectively, but no response was observed when RUP increased to 6.3% and 7.1% (CP = 17.2% and 18.0% of DM, respectively). A meta-analysis by Huhtanen and Hristov , using a large database from North America and Europe, revealed a quadratic response of milk protein yield and N use efficiency to increased MP supply, with a diminishing response when MP supply is above MP requirement. It is worth mentioning that the studies of Broderick and Bahrami-Yekdangi et al. used the NRC model to predict MP supply to meet the protein requirement of the cows, whereas the current study used the CNCPS model. Therefore, predictions from various studies can be only compared with caution because of the inevitable differences between the models. In the present study, feeding the 85% MP diets (RUP = 4.24% and 3.64% for Ayrshire cows and Holstein cows, respectively) was not sufficient to support maximal yields of milk and milk components, especially milk protein. Lee et al. reported that at similar DMI, cows produced 3.1 kg/d less milk when fed a RUP-deficient diet (RUP = 4.9% of DM, CP = 14.8%) compared with a diet that met RUP requirements (RUP = 6.1% of DM, CP = 17.6%). In another study, Metcalf et al. showed that reducing RUP (and consequently MP) from above (+12.5%) to below (-12.5%) the requirement reduced milk production by 2.3 kg/d without impairing DMI. Blouin et al. reported that reducing dietary RUP concentration while maintaining an adequate RDP level caused a decrease in the net portal absorption of total and essential AA and consequently lowered milk and milk protein yields. In the present study, the intestinal availability of AA may have been reduced when supplying 85% versus 100% MP. Such changes may be related to decreases in intake and the digestion of CP and to the lesser availability of AA from RUP when supplying 85% MP versus 100% MP. The increase in apparent CP digestibility with increasing MP supply was probably due to: (1) more CP intake associated with highly digestible CP sources (i.e., soybean and corn gluten meals) when supplying 115 versus 85% MP, and (2) a reduced proportion of metabolic endogenous fecal N at a greater MP supply relative to total fecal N compared with a relatively greater contribution at a lower MP supply. Broderick and Lee et al. also reported an increase in CP digestibility when RUP content increased. Based on these considerations, in both breeds, providing 85% of the MP requirement (versus 100% MP) may have limited AA availability for milk protein synthesis and consequently decreased milk production. In the current study, supplying 85% of the MP requirement impaired feed efficiency, expressed as kg of ECM/kg of DMI. In agreement, data of Metcalf et al. indicate a depressed feed efficiency when MP supply requirement was reduced by 12.5 and 25% mainly through reducing RUP sources in the diet. In contrast, using the NRC model to predict MP requirement, Broderick , Lee et al. , and Bahrami-Yekdangi et al. reported no effect of MP supply on feed efficiency in Holstein cows. Those studies identified diets as low or deficient when RUP concentration was 4.1-4.8% of DM, which is greater than the RUP concentration (3.6% of DM) corresponding to the 85% MP supply in the present study. On the other hand, N use efficiency were increased at 85% MP supply. Metcalf et al. and Laroche et al. both reported the improved efficiency of MP conversion to milk protein when the MP supply was 10 or 25% below the animal requirement. Fecal and urinary N excretion and energy losses in urine decreased when the MP supply was limited to 85% of the animal requirement. This was mainly due to the reduced (-14%) N intake accompanied with a smaller (-5%) decrease in milk N output when the MP supply was limited to 85% versus 100% of the animal needs. At 85% MP supply, the decrease in urinary N excretion is consistent with the reduced MUN concentration. However, such a decrease cannot be related to changes in ruminal N metabolism because ruminal NH3 concentration was unaffected, more likely due to the similar dietary RDP concentration among the experimental diets. Thus, the possible reduction in AA catabolism resulting from a reduced supply and the consequent potential decrease in blood AA concentrations may explain the observed decreases in MUN concentration and urinary N excretion. Others reported that reducing dietary RUP concentration or MP supply did not affect ruminal NH3 concentration, but reduced MUN and urinary N excretion. No additional increase in ECM or milk protein yields was achieved when MP supply increased from 100 to 115% (i.e., 438 and 385 g/d of RUP). This lack of response suggests that, at 100% MP supply, protein requirements were fulfilled and providing over MP requirement does not result in an additional gain in ECM or milk protein yields. In agreement, McCormick et al. , Broderick , and Bahrami-Yekdangi et al. reported no further increase in FCM, ECM, or milk protein yields when MP supply (and RUP) increased above the requirement of mid-lactation Holstein cows. In the present study, as a result of the linear increase in DMI as MP supply increases during the measurement of CH4 emissions, daily enteric CH4 emission (g/d) also increased given the well-established positive relationship between DMI and the amount of enteric CH4 emitted . The yield (g/kg of DMI, %GE intake) and emission intensity (g/kg of ECM) of CH4 were unaffected by the experimental treatments because of the changes that occurred in the same directions in the nominators and denominators of these ratios. Van Dorland et al. observed an increase in enteric CH4 emissions associated with a numerical increase in DMI but no effect on milk yield in cows fed a ryegrass-based diet supplemented with corn gluten meal (i.e., RUP source). On the other hand, Hynes et al. and Niu et al. reported no change in DMI, milk yield, or daily enteric CH4 production in dairy cows fed diets that were supplemented with RUP sources (soybean meal and/or canola meal). As a consequence, CH4 emission yield and intensity were unaffected in the studies of van Dorland et al. , Hynes et al. , and Niu et al. . 5. Conclusions In this study, the CNCPS (version 6.55) was used to formulate diets supplying 85%, 100%, or 115% of the MP requirement to Ayrshire and Holstein cows. Dry matter intake and milk production were less for Ayrshire cows than for Holstein cows. However, feed efficiency (kg of ECM/kg of DMI), efficiencies of the utilization of energy (milk Mcal/100 ME intake) and dietary protein for milk protein synthesis (g N milk/100 g N intake), and urinary N (g/100 g N intake) did not differ between the two breeds. Despite the greater CH4 emissions (g/d) by Holstein cows versus Ayrshire cows (as a result of a greater DMI), CH4 yield (g/kg DMI) was not different between the two breeds. Methane intensity (g/kg ECM) was also unaffected by breed, despite Ayrshire cows producing less milk than Holstein cows. Results from this study show that the responses of Ayrshire cows to an increased MP supply were not different from those of Holstein cows as energy-corrected milk or milk protein yields were not affected by breed x MP supply interaction, whereas urinary N excretion increased as dietary MP supply increased. Acknowledgments The authors are thankful to L. Croteau, M. Bechard, V. Roy, and C. Bourdeau (technical help); D. Bournival (purine derivatives analysis); S. Methot (help with statistical analyses), and the barn staff (care of the animals) all from the Sherbrooke Research and Development Centre (Agriculture and Agri-Food Canada; Sherbrooke, QC, Canada). Thanks are extended to D. Vedres (Agriculture and Agri-Food Canada; Lethbridge Research and Development Centre, Lethbridge, AB, Canada) for ammonia and volatile fatty acid analyses. The authors are grateful for the funding support of Agrinova (Alma, QC, Canada) and Agriculture and Agri-Food Canada (Ottawa, ON, Canada). Author Contributions Conceptualization, C.B.; methodology, C.B and F.H.; software, C.B. and F.H.; validation, C.B., F.H., H.L. and D.R.O.; formal analysis, F.H.; investigation, C.B. and F.H.; resources, C.B. and F.H.; data curation, F.H.; writing--original draft preparation, F.H. and C.B.; writing--review and editing, C.B., F.H., K.A.B., H.L., D.R.O. and C.C.; visualization, C.B. and F.H.; supervision, C.B. and F.H.; project administration, C.B.; funding acquisition, C.B. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Animal procedures were conducted under the approval of the local Institutional Animal Care Committee (number 566) and in accordance with the guidelines of the Canadian Council on Animal Care (Canadian Council on Animal Care, 2009). Informed Consent Statement Not applicable. Data Availability Statement All data of this study are available within the manuscript. Conflicts of Interest The authors declare no conflict of interest. animals-13-00832-t001_Table 1 Table 1 Ingredient and chemical composition of the experimental diets formulated to provide 85%, 100%, or 115% of MP requirement. Holstein Diets Ayrshire Diets MP MP Item (% of DM, Unless Otherwise Noted) 85% 100% 115% 85% 100% 115% Ingredient Corn silage 45.9 45.6 45.6 39.3 39.3 39.6 Alfalfa silage 17.3 17.2 17.5 18.5 18.6 19.1 Corn grain, ground 20.1 16.1 15.1 21.2 19.0 15.4 Soybean meal, 48% solvent-extracted 4.06 7.84 1.53 7.19 8.29 4.14 Soybean meal, heat-treated 1 0 2.10 8.16 0 1.65 7.84 Soybean hulls 3.18 1.40 - 3.59 1.04 0 Timothy hay, chopped 3.56 3.54 3.48 4.16 4.17 4.17 Corn gluten meal 0 0.78 3.11 0 2.61 4.27 Rumen inert fat supplement 2 2.70 2.25 2.44 2.87 2.21 2.65 Urea 0.50 0.28 0.28 0.38 0.10 0 Mineral and vitamin supplement 3 1.48 1.47 1.47 1.56 1.56 1.56 Calcium carbonate 0.57 0.68 0.65 0.45 0.63 0.54 Sodium bicarbonate 0.69 0.69 0.69 0.81 0.81 0.81 Chemical composition DM 43.1 43.0 42.7 43.2 43.2 42.8 OM 93.0 93.0 92.8 93.3 92.9 93.1 CP 13.1 15.4 16.5 14.3 16.1 17.5 Soluble N, % total N 52.7 40.5 36.9 43.5 33.8 28.5 NPN, % total N 40.8 30.7 28.1 34.4 25.2 21.3 NDIN, % total N 10.9 11.2 13.5 10.8 11.4 13.9 ADIN, % total N 3.80 3.63 4.20 3.73 4.11 4.40 RUP, % DM 4 3.64 5.11 6.81 4.24 5.90 7.66 RDP, % DM 4 9.50 10.26 9.73 10.03 10.17 9.88 MP, % DM 4 8.97 10.42 11.95 9.66 11.25 12.89 NDF 28.4 26.9 27.4 28.2 27.9 27.7 ADF 18.9 17.5 18.2 18.4 18.5 18.3 Starch 30.7 29.9 27.6 31.8 28.8 28.4 Ether extract 4.62 4.15 4.54 4.76 4.33 4.52 Gross energy, Mcal/kg DM 4.52 4.53 4.58 4.50 4.52 4.55 Metabolizable energy, Mcal/kg DM 4 2.66 2.67 2.69 2.65 2.65 2.67 1 Rupro Soy(r) (Benjamin Milles, St-Cesaire, QC, Canada) 2 Energy Booster(r) 100 (Milk Specialties Global Animal Nutrition, Carpentersville, IL, USA). 3 Contained 12.48% Ca, 6.80% P, 6.81% S, 7.72% Na, 1.97% K, 96 mg/kg I, 2877 mg/kg Fe, 620 mg/kg Cu, 2520 mg/kg Mn, 3777 mg/kg Zn, 83 mg/kg Co, 628,000 IU/kg vitamin A, 81,000 IU/kg vitamin D, 3739 IU/kg vitamin E, and 27.8 mg/kg Se. 4 Estimated using CNCPS (version 6.55) at DMI of 21.6 and 26.0 kg/d for Ayrshire and Holstein cows, respectively. animals-13-00832-t002_Table 2 Table 2 Dry matter intake, milk production, and milk composition of lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic DMI, kg/d 25.4 26.0 25.9 0.81 20.2 20.6 20.8 0.79 <0.01 0.12 0.44 0.84 DMI, % BW 3.65 3.74 3.71 0.143 3.58 3.64 3.65 0.135 0.70 0.20 0.32 0.88 BW, kg 700 699 701 18.7 570 569 574 18.7 <0.01 0.39 0.37 0.76 MP intake, g/d 2278 2715 3092 93.1 1956 2317 2686 106.2 0.01 <0.01 0.82 0.75 Production, kg/d Milk 41.9 45.0 44.3 1.77 31.7 32.7 34.1 1.67 <0.01 <0.01 0.04 0.05 4% FCM 2 41.0 43.3 42.9 1.64 31.9 33.1 34.4 1.61 <0.01 <0.01 0.15 0.30 ECM 3 43.6 46.5 45.9 1.71 34.5 36.1 37.4 1.66 <0.01 <0.01 0.07 0.28 Composition Fat, % 3.79 3.68 3.73 0.128 4.03 4.08 4.08 0.128 0.06 0.90 0.70 0.49 CP, % 2.99 3.09 3.08 0.062 3.33 3.44 3.39 0.059 <0.01 0.03 0.02 0.80 True protein, % 2.80 2.90 2.88 0.061 3.14 3.25 3.20 0.060 <0.01 0.03 0.02 0.82 Lactose, % 4.72 4.66 4.67 0.041 4.63 4.64 4.62 0.032 0.21 0.22 0.54 0.42 Total solids, % 12.5 12.4 12.5 0.18 12.9 13.1 13.0 0.18 0.03 0.67 0.64 0.38 SCC, log10/mL 4.37 4.42 4.40 0.156 4.35 4.43 4.37 0.136 0.94 0.66 0.35 0.93 Yield, kg/d Fat 1.61 1.68 1.68 0.074 1.28 1.34 1.38 0.071 <0.01 <0.01 0.37 0.61 Protein 1.25 1.38 1.35 0.050 1.06 1.13 1.15 0.046 <0.01 <0.01 0.01 0.31 Lactose 1.97 2.10 2.07 0.074 1.47 1.52 1.57 0.073 <0.01 <0.01 0.10 0.16 MUN, mg/dL 6.67 10.41 12.62 0.537 6.07 8.88 11.4 0.494 0.07 <0.01 0.18 0.47 Feed efficiency Milk/DMI 1.65 1.72 1.71 0.043 1.57 1.59 1.64 0.042 0.10 <0.01 0.36 0.36 ECM/DMI 1.71 1.78 1.77 0.030 1.71 1.75 1.80 0.032 0.97 <0.01 0.59 0.58 N use efficiency, g N milk/100 g N intake 36.8 33.9 31.1 0.78 35.9 33.3 30.9 0.59 0.53 <0.01 0.84 0.71 1 Least square means from 6 Latin squares (18 cows) 2 4% fat corrected milk (FCM) = 0.4 x milk yield (kg/d) + 15 x fat yield (kg/d). 3 ECM = 0.327 x milk yield (kg/d) + 12.95 x fat yield (kg/d) + 7.2 x protein yield (kg/d). animals-13-00832-t003_Table 3 Table 3 Ruminal pH of lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic pH Mean 6.29 6.32 6.31 0.086 6.44 6.29 6.27 0.083 0.82 0.10 0.53 0.07 Minimum 5.74 5.72 5.77 0.105 5.92 5.75 5.75 0.130 0.67 0.23 0.20 0.21 Maximum 6.74 6.84 6.78 0.061 6.88 6.76 6.83 0.060 0.59 0.89 0.84 0.11 Time pH < 6.0, min/d 223 154 133 140.0 140 280 298 132.9 0.67 0.71 0.81 0.37 Time pH < 5.6, min/d 20 7 1 8.3 0 14 4 6.6 0.60 0.29 0.52 0.13 1 Least square means from 4 Latin squares (12 cows). animals-13-00832-t004_Table 4 Table 4 Total VFA concentration, VFA molar proportions, NH3 concentration, and protozoa number in ruminal fluid of lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic Total VFA, mM 134 134 137 4.1 131 135 131 4.2 0.60 0.59 0.67 0.46 VFA, mol/100 mol Acetate 63.9 62.5 63.3 1.48 61.5 61.0 60.5 1.57 0.26 0.37 0.45 0.73 Propionate 19.1 20.1 20.2 1.83 22.5 23.4 22.9 1.82 0.17 0.45 0.53 0.91 Butyrate 11.1 11.7 10.9 0.38 10.8 10.5 11.6 0.57 0.61 0.46 0.98 0.11 Isobutyrate 0.88 0.87 0.83 0.315 0.89 0.88 0.88 0.029 0.44 0.29 0.77 0.59 Valerate 1.72 1.60 1.74 0.083 1.62 1.77 1.57 0.158 0.78 0.89 0.81 0.23 Isovalerate 2.38 2.14 1.87 0.249 1.98 1.80 1.85 0.136 0.17 0.10 0.76 0.53 Acetate:Propionate 3.45 3.18 3.21 0.294 2.95 2.73 2.83 0.262 0.22 0.30 0.28 0.51 NH3, mM 6.93 8.08 8.00 0.587 8.69 8.27 8.01 0.422 0.20 0.68 0.51 0.93 Protozoa, cell x 103/mL 627 690 574 70.4 408 457 456 57.2 0.01 0.94 0.29 0.14 1 Least square means from 4 Latin squares (12 cows). animals-13-00832-t005_Table 5 Table 5 Apparent total-tract digestibility (%) of nutrients in lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic DM 67.4 68.1 69.2 0.75 70.1 70.6 70.2 0.77 0.04 0.12 0.75 0.30 OM 69.0 69.9 70.8 0.79 71.7 72.2 72.0 0.75 0.03 0.10 0.82 0.44 CP 61.7 65.9 67.6 1.00 65.6 68.7 69.2 0.86 0.01 <0.01 0.12 0.46 NDF 37.6 39.1 39.6 1.61 44.2 42.0 43.8 1.94 0.05 0.52 0.50 0.34 ADF 36.1 37.8 38.7 2.37 43.6 40.7 41.9 1.51 0.02 0.84 0.63 0.43 Starch 97.5 97.9 98.3 0.29 97.6 98.1 98.3 0.41 0.77 0.04 0.89 0.94 Gross energy 66.7 67.8 68.7 0.86 69.8 70.1 70.0 0.74 0.02 0.09 0.78 0.39 1 Least square means from 4 Latin squares (12 cows). animals-13-00832-t006_Table 6 Table 6 Enteric methane production of lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic DMI, kg/d 2 25.5 26.0 26.3 1.13 19.4 20.2 20.9 1.06 <0.01 0.01 0.72 0.53 CH4 g/d 454 487 510 37.3 376 390 391 35.3 0.06 0.03 0.67 0.42 g/kg DMI 17.7 19.1 19.6 1.34 19.1 19.2 18.6 1.34 0.93 0.27 0.59 0.14 g/kg milk 3 10.8 11.4 11.9 1.14 12.0 12.3 11.9 1.09 0.66 0.21 0.55 0.30 g/kg ECM 3 10.1 10.8 11.3 0.85 10.8 10.9 10.6 0.82 0.94 0.21 0.65 0.20 1 Least square means from 4 Latin squares (12 cows) 2 Determined for 5 consecutive days in the chambers. 3 Yields of milk, ECM, milk fat, and milk protein measured over the 7-d collection periods. animals-13-00832-t007_Table 7 Table 7 Energy intake, expenditure and partitioning in lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM P 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic Intake, Mcal/d Gross energy 116 118 117 5.5 91.7 92.5 94.3 4.9 0.01 0.57 0.86 0.84 Digestible energy 77.8 79.8 80.1 3.68 63.9 64.8 66.0 3.19 0.01 0.22 0.80 0.94 ME 69.3 70.2 70.0 3.36 56.9 57.3 58.1 2.74 0.01 0.59 0.91 0.94 NE 2 40.0 40.8 40.6 2.00 32.4 33.1 34.0 1.73 0.01 0.24 0.79 0.81 Energy expenditureMcal/d Fecal 38.6 37.9 36.7 2.16 27.8 27.8 28.3 1.97 <0.01 0.57 0.99 0.56 Urine 2.28 2.95 3.38 0.148 2.01 2.39 2.67 0.152 0.01 <0.01 0.36 0.15 Methane 6.00 6.44 6.73 0.492 4.96 5.14 5.16 0.465 0.06 0.03 0.67 0.42 Heat 3 35.0 35.0 35.2 1.20 28.1 28.1 28.7 1.10 <0.01 0.31 0.56 0.76 Milk 29.7 30.3 30.8 1.56 23.2 24.1 24.8 1.55 0.01 0.03 0.90 0.93 Maintenance 4 10.7 10.5 10.7 0.35 9.18 9.18 9.27 0.308 0.01 0.57 0.11 0.48 % GE intake Fecal 33.3 32.2 31.3 0.86 30.2 29.9 30.0 0.74 0.02 0.09 0.78 0.39 Urine 2.01 2.55 2.90 0.095 2.19 2.58 2.85 0.117 0.56 <0.01 0.40 0.57 Methane 5.18 5.54 5.66 0.387 5.57 5.55 5.34 0.388 0.96 0.47 0.46 0.14 Heat 3 30.7 30.3 30.9 0.82 30.8 30.6 30.5 0.71 0.99 0.99 0.51 0.77 Milk 25.4 25.5 26.4 0.60 25.3 26.1 26.3 0.55 0.82 0.04 0.87 0.75 Maintenance 4 9.41 9.09 9.40 0.539 10.10 10.10 9.90 0.478 0.29 0.68 0.64 0.61 Milk energy, % ME 42.8 43.1 44.6 1.39 40.8 42.0 42.7 1.04 0.22 0.10 0.87 0.88 1 Least square means from 4 Latin squares (12 cows) 2 NE = dietary NE concentration x DMI 3 Heat energy calculated using the equation 6.34 in INRA : log10 (heat energy) = 1.54 + 0.95 x log10 BW + 0.54 x log10 DMI%BW 4 Maintenance energy calculated according to NRC = 0.080 x BW0.75. animals-13-00832-t008_Table 8 Table 8 Nitrogen utilization in lactating Holstein and Ayrshire cows fed diets formulated to provide 85%, 100%, or 115% of metabolizable protein (MP) requirement 1. Holstein Ayrshire MP SEM MP SEM p 85% 100% 115% 85% 100% 115% Breed MP Breed x MP Item Linear Quadratic Intake N, g/d 552 654 684 29.1 476 543 594 26.6 0.03 <0.01 0.08 0.46 Fecal N g/d 211 224 223 13.4 163 171 183 11.1 0.01 0.08 0.74 0.77 % of N intake 38.3 34.1 32.4 1.00 34.4 31.3 30.7 0.86 0.01 <0.01 0.12 0.46 Urinary N g/d 119 186 228 11.4 109 150 182 9.0 0.02 <0.01 0.22 0.07 % of N intake 22.1 28.6 33.3 1.19 22.9 27.8 30.8 0.98 0.33 <0.01 0.35 0.32 Total N excretion g/d 329 409 451 22.8 273 321 365 18.7 0.01 <0.01 0.38 0.45 % of N intake 60.4 62.8 65.8 1.66 57.3 59.1 61.5 1.30 0.01 0.01 0.79 0.93 Milk N g/d 203 215 211 10.3 165 174 180 10.5 0.03 0.01 0.16 0.33 % of N intake 36.6 32.7 30.9 1.05 34.6 32.2 30.4 0.75 0.39 0.01 0.21 0.41 Urinary PD 2, mmol/d Allantoin 443 443 395 24.2 328 345 312 25.5 <0.01 0.10 0.14 0.68 Uric acid 53.5 54.2 56.3 5.13 30.7 35.9 33.8 4.60 0.01 0.22 0.48 0.58 Total PD 497 497 451 27.6 359 381 346 28.9 <0.01 0.17 0.16 0.70 1 Least square means from 6 Latin squares (12 cows) 2 Purine derivatives. animals-13-00832-t009_Table 9 Table 9 Prediction of metabolizable protein and metabolizable energy in Ayrshire cows using the experimental diets formulated to Holstein cows. MP Item 85% 100% 115% Metabolizable protein Requirement, g/d 1 2410 2410 2410 Supply, g/d 1951 2245 2604 Supply, % requirement 80.9 93.8 109 Allowable milk, kg/d 26.2 32.8 40.6 Metabolizable energy Requirement, Mcal/d 1 58.1 58.1 58.0 Supply, Mcal/d 57.6 57.3 58.3 Supply, % requirement 99.4 98.8 100.4 Allowable milk, kg/d 35.7 35.4 36.2 1 Requirement when fed breed-specific diet. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000242 | Although many devices have been developed to reduce sample volume, with an explosion of methods appearing in the literature over the last decade, commercially available devices with simultaneous vitrification of a larger number of embryos are scarce, with the apparent gap for their use in prolific livestock species. In this study, we investigated the effectiveness of a new three-dimensional (3D)-printed device that combines minimum volume cooling vitrification with simultaneous vitrification of a larger number of rabbit embryos. Late morulae/early blastocysts were vitrified with the open Cryoeyelet(r) device (n = 175; 25 embryos per device), the open Cryotop(r) device (n = 175; 10 embryos per device), and the traditional closed French mini-straw device (n = 125; 25 embryos per straw) and compared in terms of in vitro development and reproductive performance after transfer to adoptive mothers. Fresh embryos constituted the control group (n = 125). In experiment 1, there was no difference in the development rate to the blastocyst hatching stage between the CryoEyelet(r) and the other devices. In experiment 2, the CryoEyelet(r) device showed a higher implantation rate compared with the Cryotop(r) (6.3% unit of SD, p = 0.87) and French mini-straw(r) (16.8% unit of SD, p = 1.00) devices. In terms of offspring rate, the CryoEyelet(r) device was similar to the Cryotop(r) device but superior to the French straw device. Regarding embryonic and fetal losses, the CryoEyelet(r) showed lower embryonic losses compared to other vitrification devices. The analysis of bodyweight showed that all devices showed a similar outcomes--a higher birthweight but a lower body weight at puberty than those in the fresh transfer embryos group. In summary, the CryoEyelet(r) device can be used for the vitrification of many late morulae or early blastocyst stage rabbit embryos per device. Further studies should be performed to evaluate the CryoEyelet(r) device in other polytocous species for the simultaneous vitrification of a large number of embryos. cryopreservation rabbit morulae blastocyst MCIN/AEI/10.13039/501100011033European Union "NextGenerationEU"/PRTRPDC2021-120767-I00 This research was funded by the Funded by MCIN/AEI/10.13039/501100011033 and by the European Union "NextGenerationEU"/PRTR (PDC2021-120767-I00). pmc1. Introduction Embryo cryopreservation has been a valuable tool for embryology since its first success in 1972 . This technology is the best method for preserving valuable genetic resources from livestock animals . Cryopreservation is also required for the widespread use of embryo transfer, which enables the exchange of genetics resources with reduced transportation cost, avoiding animal welfare problems and with minimal risk of disease transmission . Undoubtedly, embryo cryopreservation is routinely used in bovine commercial embryo transfer (ET) programs. Nevertheless, commercial cryopreserved embryo transfer program for other livestock species is non-available . In part, the difficulty and high cost of obtaining large numbers of embryos in these species have limited the number of cryopreservation studies performing ET transmission . Nowadays, there is a considerable requirement for efficient and valuable porcine embryo cryopreservation procedures for commercial use in the swine industry as well as for genetic diversity preservation and biomedical research studies . For prolific livestock species, the main handicap of vitrification is the low number of embryos that commercial devices can hold transmission . Although attempts have been made to generate systems that allow cryopreservation of large numbers of embryos, such as hollow fiber or the easily accessible paper container method , commercial, large holding capacity devices for minimum volume cooling vitrification of oocytes or embryos are non-existent. For rabbits, however, using the French straw device (without limitation on the number of embryos to be stored by device) provides an acceptable offspring production efficiency calculated as the ratio of the number of birth kits to the number of embryos transferred (ranging from 25% to 65%, ), while in pigs, when using the open pulled straw (OPS) method (from five to seven embryos by device) a lower offspring production efficiency has been reported (ranging from 7.1% to 23%, . Given that 30-40 embryos are required to perform one transfer to obtain a physiological pregnancy, the ideal is to develop a system based on the minimum essential volume that allows the simultaneous vitrification of a sufficient number of embryos in a single device to carry out a single on-farm transfer . This means that six to eight superfine open pulled-straw (SOPS) straws must be warmed to complete a single embryo transfer . Recently, Gonzalez-Plaza et al. demonstrated the feasibility of simultaneous vitrification of 20 morulae and blastocysts with the Cryotop(r) device using drops with 1 to 3 embryos (0.5-1 mL each drop) that are loaded with a glass pipette stretched along the entire surface of the polypropylene sheet. This study aimed to develop a 3D-printed device with a large holding capacity device for preimplantation embryos using the minimum volume method. Using rabbits as a model, the specific objectives were to (i) design and fabricate the device called Cryoeyelet(r), (ii) evaluate the in vitro development efficiency, (iii) evaluate the rate of offspring, and (iv) analyze the effects on offspring phenotype compared with the Cryotop(r) and the French mini-straw(r) devices. 2. Materials and Methods Unless otherwise noted, all chemicals were purchased from Sigma-Aldrich Qumica S.A. and were of the reagent grade (Alcobendas, Madrid, Spain). 2.1. Design and 3D Printing of CryoEyelet(r) Device The overall design goal was to create a device that could suspend a thin film within a loop with an outer cover that hermetically seals the device, optimizing space in the nitrogen tanks. The Cryoeyelet(r) device (EP-3957715-A) is an open vitrification device consisting of a single piece . It includes a slender holding portion configured for holding and labeling the sample, having an intermediate portion connected to a tip and a pointed distal end comprising a hole with an elliptical configuration. Based on the preliminary trials of sample loading and vitrification feasibility, the loop (inner measures) of the vitrification component was designed with a major axis of 8.8 mm (referred to as 'loop lengths') and 0.6 mm of the minor axis (referred to as 'loop widths'). With these dimensions, the device can be stored inside the straw covers. The overall length is 140 mm, which allows for storage on standard goblets in biobanks. Furthermore, the geometry allows forming a thin film of vitrification solution, where the embryos are in direct contact with the liquid nitrogen on their entire surface. This furthermore entails excellent ease of use by the handler since, once the sample is deposited on the support, no additional steps are required to reduce the volume of the cryoprotective solution. Likewise, the device provides both individual and large number storage of ova or embryos. Moreover, the holding portion of the support allows labeling with the relevant information being easy to visualize. The 3D model design was created using additive manufacturing, which reduced waste and cost. The 3D technology is stereolithography (STL), and the files developed in design with all variations were fabricated in free cutting software (Chitubox Pro, ) to define the printer settings and the fabrication supports. The settings were loaded into an Elego Mars Saturn 3D-printer and printed in photosensitive resin. Each device took approximately 20 min to manufacture, with a material cost of EUR 1. 2.2. Animals New Zealand white rabbits were used under farm conditions. Briefly, animals were housed at the Universitat Politecnica de Valencia experimental farm in flat deck indoor cages (75 x 50 x 30 cm), with free access to water and commercial pelleted diets (minimum of 15 g of crude protein per kg of dry matter (DM), 15 g of crude fiber per kg of DM, and 10.2 MJ of digestible energy (DE) per kg of DM). The photoperiod is set to provide 16 h of light and 8 h of dark, and the room temperature is regulated to keep temperatures between 10 degC and 28 degC. 2.3. Collection of Embryos at the Late-Morulae Early Blastocyst Stage Seventeen nulliparous New Zealand white does were superstimulated with a combination of follicle-stimulating hormone (FSH) (Corifollitropin alfa, 3 mg, Elonva, Merck Sharp & Dohme S.A.) and hCG (7.5 UI) . Seventy-two hours after superstimulation, dams were inseminated with pooled semen from New Zealand bucks of proven fertility. Ovulation was induced with 1 mg buserelin acetate (Suprefact; Hoechst Marion Roussel, S.A., Madrid, Spain). Females were euthanized 72 h after artificial insemination, and the reproductive tract was immediately removed. Embryos were recovered by flushing each uterine horn with 10 mL Dulbecco's phosphate-buffered saline containing 0.2% (wt/vol) bovine serum albumin (BSA). Collected embryos were counted and evaluated following the International Embryo Technology Society (IETS) criteria. Briefly, only embryos in late morulae/early blastocyst stages with homogenous cellular mass and spherical mucin coat and zona pellucida were catalogued as suitable (transferable) embryos. 2.4. Vitrification and Warming Procedure Embryos were vitrified according to the methodology described by Marco-Jimenez et al. . Briefly, embryos were vitrified in a two-step addition procedure. At vitrification time, embryos were transferred into an equilibration solution consisting of 10% (vol/vol) ethylene glycol and 10% (vol/vol) dimethyl sulfoxide dissolved in a base medium (BM; Dulbecco's phosphate buffered saline (DPBS) supplemented with 0.2% [wt/vol] BSA) at room temperature (22-25 degC) for 2 min. The embryos were then transferred to a vitrification solution consisting of 20% (vol/vol) ethylene glycol and 20% (vol/vol) dimethyl sulfoxide in BM and loaded into the devices and directly plunged into LN2 within 1 min. For the CryoEyelet(r) (n = 175) and French mini-straw devices (n = 125), a total of 25 embryos were stored in each device, while 10 embryos were stored in each Cryotop(r) (n = 175). For the CryoEyelet(r) storage, the device was placed under a microscope and the focus on the eyelet area was adjusted. The embryos were aspirated with a pipette in 2 mL of the vitrification solution. The microdrop was expelled with the embryos gently in the proximal part of the eyelet and the drop was slid towards the distal part. Thus, the film of the vitrification solution containing the embryos was distributed over the entire surface of the eyelet with a low-thickness layer. After storage in liquid nitrogen (1 month), stored embryos were placed into CryoEyelet(r) and Cryotop(r) devices and were warmed by abrupt immersion of the naked devices into a Petri plate (P35) containing 0.33 M sucrose solution at 25 degC in BM for 5 min and subsequently transferred to BM solution for 5 min. The embryo warming procedure used for the French mini-straw device was based on the one-step dilution method . Straws containing the embryos were removed from the liquid nitrogen and placed horizontally 10 cm from the liquid nitrogen vapor for 20-30 s. When the crystallization process began inside the mini-straw, the mini-straw was immersed in a water bath at 25 degC for 10-15 s. The mini-straw content was expelled into a plate containing 0.33 M sucrose solution at 25 degC in BM for 5 min and subsequently transferred to BM solution for 5 min. Warming embryos were scored, and only undamaged embryos were catalogued as culturable/transferable. 2.5. Effect of Vitrification Device on the In Vitro Development Embryos were cultured in 500 mL of SAGE 1-StepTM HSA (CooperSurgical, Barcelona, Spain) under paraffin oil (Hypure(r) heavy, Kitazato, Distribed, Valencia, Spain) in four well plates for 48 h at 38.5 degC in a humidified atmosphere of 5% CO2 in the air. After culture, embryos were evaluated morphologically under a stereomicroscope for their developmental progression until the hatching/hatched blastocyst stage. 2.6. Effects of the Device on the Implantation Rate, Offspring Rate at Birth and Embryonic and Fetal Losses Between 64 and 66 h before transfer, recipient does were synchronized by intramuscular administration of 1 mg i.m. of buserelin acetate (Hoechst, Marion Roussel, Madrid, Spain). Only females that presented vulva color associated with receptive status were induced to ovulate. On the day of the embryo transfer, does were anesthetized by an i.m. injection of 4 mg/Kg of xylazine (Bayer AG, Leverkusen, Germany), followed 5-10 min later by intravenous injection into the marginal ear vein of 0.4 mL/Kg of body mass of ketamine hydrochloride (Imalgene 500, Merial SA, Lyon, France) . During laparoscopy, 3 mg/kg of morphine hydrochloride (Morfina, B. Braun, Barcelona, Spain) was administered intramuscularly. Between 10-12 cryopreserved and fresh embryos were transferred per recipient (5-6 embryos into each oviduct). After transfer, does were treated with antibiotics (4 mg/kg of gentamicin every 24 h for 3 days, 10% Ganadexil, Invesa, Barcelona, Spain) and analgesics (0.03 mg/kg of buprenorphine hydrochloride, [Buprex, Esteve, Barcelona, Spain] every 12 h for 3 days and 0.2 mg/kg of meloxicam [Metacam 5 mg/mL, Norvet, Barcelona, Spain] every 24 h for 3 days). The survival rate was assessed by laparoscopy following the previous procedure, noting implantation rate (number of implanted embryos at day 14 from total embryos transferred) and birth rate (offspring born/total embryos transferred). Embryonic losses were calculated as the difference between embryos transferred and implanted embryos. Fetal losses were calculated as the difference between total born at birth and implanted embryos. 2.7. Effect of Vitrification Device on Postnatal Growth Performance Body mass differences between each progeny (CryoEyelet(r), Cryotop(r), French mini-straw(r) and fresh) were assessed at birth, 4th week (weaning), and 9th week (prepubertal age). 2.8. Statistical Analyses Differences between CryoEyelet(r) and other vitrification devices (Cryotop(r) and French mini-straw(r)) and the fresh group were estimated using Bayesian inference. The dendrogram obtained by Bayesian interference was created by 60,000 interactions of Markov chain Monte Carlo, with a burn-in period of 10,000, saving only 1 of every 10 samples for inference. The parameters obtained from the marginal posterior distributions of the relative abundance between groups were the mean of the difference (DCryoEyelet(r)-j; computed as CryoEyelet(r)-j, being j the Cryotop(r), French mini-straw(r) and fresh groups), the probability of the difference being greater than 0 when DCryoEyelet(r)-j > 0 or lower than 0 when DCryoEyelet(r)-j < 0 (P0), and the highest posterior density region at 95% of probability (HPD95%). Di-j estimated the mean of the differences between i and j traits, P0 estimated the probability of DCryoEyelet(r)-j 0, and HPD95% estimated the accuracy. Statistical difference was considered if P0 > 0.8 (80%). Statistical analysis was computed with the rabbit program developed by the Institute for Animal Science and Technology (Valencia, Spain). 3. Results A total of 600 embryos were utilized, from which 225 were used to evaluate the in vitro hatching rates (in vitro assay distributed in each group as follows: CryoEyelet(r) n = 75, Cryotop(r) n = 75, French Straw(r) n = 50, and Fresh n = 20), and 375 were transferred to foster mothers (n = 37) to evaluate the offspring rate (distributed in each group as follows: CryoEyelet(r) n = 100, Cryotop(r) n = 100, French Straw(r) n = 100, and Fresh n = 75). Descriptive data of traits are annotated in Table 1. In experiment 1, there was no difference in the development rate to the blastocyst hatching stage between CryoEyelet(r) and the other devices (Table 2), but CryoEyelet(r) results slightly decreased compared to the fresh group (-6.3% unit of SD, p = 0.80, Table 2). In experiment 2, CryoEyelet(r) showed a higher implantation rate compared with Cryotop(r) (6.3% unit of SD, p = 0.87, Table 2) and French mini-straw(r) devices (16.8% unit of SD, p = 1.00, Table 2). There was no difference between CryoEyelet(r) and the fresh group (Table 2). In terms of offspring rate, CryoEyelet(r) was similar to Cryotop(r) (Table 2) but superior to the French straw device. As expected, the results of the CryoEyelet(r) device were inferior to the fresh group (-13.2% SD unit, p = 0.97, Table 2). Regarding embryonic and fetal losses, CryoEyelet(r) showed lower embryonic losses compared to other vitrification devices (Table 2), while fetal losses were the same as with the Cryotop(r) device but again lower than with the French straw device (Table 2). The embryonic losses were similar to the fresh group but higher in fetal losses (Table 2). At birth, offspring derived by the CryoEyelet(r) device exhibited a higher bodyweight compared to the other devices and the fresh group (using the litter size covariate 8.96, significant effect at p < 0.05, Table 3). At weaning (4 weeks old), kits derived from CryoEyelet(r) showed a similar bodyweight to the Cryotop(r) device but a higher bodyweight compared to the French straw devices (55.4 g SD unit, p = 0.92, Table 3). At rearing (9 weeks old), animals derived from CryoEyelet(r) exhibited similar bodyweight to the other devices (Table 3) but were higher than the fresh group (-132.2 g SD unit, p = 0.91, Table 3). 4. Discussion In this study, we showed a simple, low-cost, 3-D printable, practical vitrification device based on the minimum volume method for the simultaneous vitrification of a large number of rabbit embryos. Our findings revealed that the CryoEyelet(r) is a suitable system for the simultaneous vitrification of almost 25 rabbit embryos at the late morula/early blastocyst stages, with efficiency in terms of in vitro and in vivo development similar to the Cryotop(r) device, considered one of the gold standards for human gamete cryopreservation . Although a great number of devices have been developed to reduce sample volume over the last decade , with some of the cryodevices being commercially available (e.g., Cryotop(r)/Cryotop(r)CL, Cryolock(r), CryoTip(r), and Diamour-op/Diamour-cs), devices for the simultaneous vitrification of a large number of embryos are scarce, with the apparent gap for their use in prolific livestock species . To vitrify a large number of embryos not only greatly simplifies the current vitrification protocols in prolific livestock species but also facilitates the embryo warming and embryo transfer processes, generally performed under field conditions (one device/one transfer, ). Three-dimensional (3-D) printing and computer-aided design (CAD) offer practical ways to quickly design and construct devices that can support cryogenic applications due to their fast expanding consumer-level capabilities . Thus, the work presented herein produced a 3D-printed vitrification device based on the cryoloop procedure that can store almost 25 rabbit preimplantational embryos and can be accommodated in 0.25 mL straws for space optimization during storage. With the CryoEyelet(r) device, there was no difference in the ability of preimplantational embryos to hatch in vitro. Vitrification using the French mini straw(r) and Cryotop(r) devices and the loop procedure (calibrated plastic inoculation loop, ) were previously used to successfully vitrify late-morulae/early-blastocyst stage rabbit embryos. Similar to this study, the in vitro viability of rabbit embryos vitrified at the late-morulae/early-blastocyst stage does not appear to be affected by the device used . Thus, the CryoEyelet(r), Cryotop(r), and French mini-straw(r) devices show a similar and excellent in vitro development capacity. Regardless of the device used, the in vitro results were close to the fresh group. The ultimate test of the viability of embryos after cryopreservation is the ability to establish and maintain a pregnancy, resulting in normal fertile young . In this study, the implantation rates of rabbit late-morulae/early-blastocysts vitrified with the CryoEyelet(r) were higher than that of the Cryotop(r) (+6.3%) and French mini-straw(r) (+16.8%) embryos. Moreover, the implantation rates of vitrified embryos with the CryoEyelet(r) were similar to that of fresh embryos. In terms of offspring rate, CryoEyelet(r) was similar to Cryotop(r) but superior to the French straw (8.5%) device. Until now, the Cryotop device has provided the most successful rate of offspring at birth in rabbits . However, the Cryotop vitrification device is expensive for livestock applications and conservation-focused biobanks, with an average cost of USD 20-30 per sample, which only seems justifiable for human fertility clinics. In addition, the Cryotop(r) system typically stores only 1-4 oocytes or embryos at a time, a process which is performed by skilled embryologists. In our study, 10 embryos were successfully placed and vitrified in each Cryotop(r) device according to the manufacturer's instructions. Recently, Gonzalez-Plaza et al. demonstrated that Cryotop(r) is suitable for the simultaneous vitrification of at least 20 porcine embryos at the morula or blastocyst stage by forming steric droplets (groups of 1-3 embryos in 0.5-1 mL) along the polypropylene sheet. A notable advantage of the CryoEyelet(r) device is its ease of use, making it accessible to embryologists unfamiliar with the Cryotop(r) device. Additionally noteworthy is that the CryoEyelet(r) device is considerably lower in cost (the retail cost could be roughly USD 3 per sample) compared with the commercial vitrification devices based on minimum essential volume. Due to this reason, multi-ovulation and embryo-transfer (MOET) intervention appear to influence measurable outcomes of offspring physiology, manifesting differently across the species studied , including rabbits ; we investigated the impact of the vitrification device on postnatal bodyweights. Previously, we reported that animals born combined MOET with cryopreservation exhibit higher birthweight and poor growth performance independently of the vitrification device using a rabbit model . Newly, here we demonstrated that animals born after embryo cryopreservation exhibit higher birthweight and poor growth performance independently of the device used, in line with several studies in different mammalian species, including humans . Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations . All devices show a similar outcome concerning the bodyweight, a higher birthweight but a lower body weight at puberty than those in the fresh transfer embryos group. The main limitation of our results is related to the limited literature that compared offspring outcomes following vitrification compared several devices. Given the mounting evidence from both animal and human research that offspring born after the use of ART may exhibit physiologic alterations from those who are spontaneously conceived, more significant consideration of the vitrification devices used for more precise decision-making regarding the application of this technology . Further studies would be of interest, as they allow these effects to be studied in other species. 5. Conclusions In summary, the CryoEyelet(r) device can be used for the vitrification of a high number of late morulae or early blastocyst rabbit embryos per device, yielding similar outcomes to the most used commercial device based on minimum essential volume. Further studies should be performed to evaluate the successful vitrification with the CryoEyelet(r) device with many embryos in other polytocous species. Acknowledgments We would like to thank Printable ) for their collaboration in developing and manufacturing this new device. Author Contributions Conceptualization, F.M.-J. and J.S.V.; methodology, F.M.-J., J.S.V., X.G.-D. and L.G.-V.; data curation, F.M.-J., J.S.V., X.G.-D. and L.G.-V.; writing--original draft preparation, F.M.-J.; writing--review and editing, F.M.-J., X.G.-D. and J.S.V. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The experimental protocol used in this study was approved by the Ethical Review Panel of the Directorate-General for Agriculture, Fisheries, and Livestock of the Valencian Community, under code 2018/VSC/PEA/0116). Informed Consent Statement Not applicable. Data Availability Statement The original contributions presented in the study are included in the article/supplementary material, and further inquiries can be directed to the corresponding authors. Conflicts of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Figure 1 Vitrification device design and 3D-printing prototype. (A) Full device rendering. (B) Detail of the gamete and embryo deposition area. (C) 3D-printed device with a cap to generate a closed system. animals-13-00791-t001_Table 1 Table 1 Summary of the traits and means from each experimental group analyzed. Trait CryoEyelet(r) Cryotop(r) French Straw(r) Fresh In vitro development (%) 89.3 88.3 90.2 95.4 Implantation rate (%) 84.3 78.0 67.5 87.5 Offspring rate (%) 60.7 65.1 52.3 73.9 Losses (%) Embryonic 15.5 21.9 32.5 12.5 Fetal 30.3 31.0 22.3 15.5 Bodyweight (g) At birth 64.7 54.5 53.6 47.7 At weaning 513.0 523.2 457.6 498.8 At prepubertal age 1560.1 1521.5 1692.3 1547.9 animals-13-00791-t002_Table 2 Table 2 Embryo viability rates differences using CryoEyelet(r), Cryotop(r), and French Straw(r) devices and a fresh control group. Data computed as CryoEyelet(r)-Cryotop(r), CryoEyelet(r)-Straw(r) and CryoEyelet(r)-Fresh. Trait Device Comparisons CryoEyelet(r)-Cryotop(r) CryoEyelet(r)-French Straw(r) CryoEyelet(r)-Fresh Di-j P0 HPD95% Di-j P0 HPD95% Di-j P0 HPD95% In vitro development (%) 7.8 0.56 -9.67, 11.36 -1.1 0.58 -12.22, 9.25 -6.3 0.80 -22.28, 7.54 Implantation (%) 6.3 0.87 -4.44, 17.64 16.8 1.00 5.78, 28.49 -3.2 0.72 -15.27, 7.55 Offspring rate (%) -4.4 0.75 -17.54, 8.79 8.5 0.89 -5.12, 22.19 -13.2 0.97 -27.29, -0.18 Losses (%) Embryonic -6.4 0.88 -17.62, 4.05 -0.2 1.00 -27.94, -5.29 30.9 0.71 -8.01, 13.84 Fetal -0.7 0.55 -14.16, 11.26 7.9 0.86 -6.98, 21.85 14.8 0.99 1.61, 27.37 Di-j = mean of the difference between i-j devices (median of the marginal posterior distribution of the difference between the i and j devices); P0 = probability of the difference (Di-j) being greater than 0 when i-j > 0 or lower than 0 when Di-j < 0; HPD95% = the highest posterior density region at 95% of probability. Statistical differences were assumed if P0 > 0.80. animals-13-00791-t003_Table 3 Table 3 Bodyweight progenies differences using CryoEyelet(r), Cryotop(r), and French Straw(r) devices and fresh control group. Data computed as CryoEyelet(r)-Cryotop(r), CryoEyelet(r)-Straw(r) and CryoEyelet(r)-/Fresh. Bodyweight (g) Device Comparisons CryoEyelet(r)-Cryotop(r) CryoEyelet(r)-French Straw(r) CryoEyelet(r)-Fresh Di-j P0 HPD95% Di-j P0 HPD95% Di-j P0 HPD95% At birth 10.3 1.00 5.06, 15.48 11.1 1.00 6.14,16.25 16.9 1.00 10.09, 23.57 At weaning -10.2 0.60 -94.34, 70.54 55.4 0.92 -23.76, 133.60 14.2 0.60 -101.89, 117.94 At rearing 38.6 0.70 -107.49, 183.91 12.2 0.57 -126.80, 153.04 -132.2 0.91 -326.06, 68.83 Di-j = mean of the difference between i-j devices (median of the marginal posterior distribution of the difference between the i and j devices); P0 = probability of the difference (Di-j) being greater than 0 when i-j > 0 or lower than 0 when Di-j < 0; HPD95% = the highest posterior density region at 95% of probability. Statistical differences were assumed if P0 > 0.80. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000243 | Background. Bladder carcinoma has elevated morbimortality due to its high recurrence and progression in localized disease. A better understanding of the role of the tumor microenvironment in carcinogenesis and response to treatment is needed. Methods. Peripheral blood and samples of urothelial bladder cancer and adjacent healthy urothelial tissue were collected from 41 patients and stratified in high-grade urothelial bladder cancer, excluding muscular infiltration or carcinoma in situ. Mononuclear cells were isolated and labeled for flow cytometry analysis with antibodies aimed at identifying specific subpopulations within T lymphocytes, myeloid cells and NK cells. Results. In peripheral blood and tumor samples, we detected different percentages of CD4+ and CD8+ lymphocytes, monocyte and myeloid-derived suppressor cells, as well as differential expression of exhaustion-related markers. Conversely, only a significant increase in bladder total monocytes was found when comparing bladder and tumor samples. Interestingly, we identified specific markers differentially expressed in the peripheral blood of patients with different outcomes. Conclusion. The analysis of host immune response in patients with NMIBC may help to identify specific markers that allow optimizing therapy and patient follow-up. Further investigation is needed to establish a strong predictive model. bladder cancer immunotherapy immune response T-cells tumor microenvironment biomarkers Instituto de Salud Carlos IIIPI19/00549 PI22/01542 This research was funded by Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III, grant numbers PI19/00549 and PI22/01542 to A.A. pmc1. Introduction Bladder cancer has high morbidity and mortality , and it represents a significant global public health issue due to the high recurrence rate and progression in localized stages . Once diagnosed, these patients may require different intravesical treatments, and advanced and metastatic diseases usually need complex surgical and systemic therapies. Therefore, this condition is currently considered a pathology with high consumption of economic resources . Approximately 75% of bladder cancers are confined to the urothelial mucosa , which has different prognostic and therapeutic implications than those affecting the bladder muscle. Approximately 90% of bladder tumors are urothelial carcinoma, followed by squamous cell carcinoma (1-7%) and, to a much lesser extent, by adenocarcinoma (0.5-2%) . Transurethral Resection of Bladder Tumor (TURB) is the main approach to diagnosing and treating non-muscle-invasive bladder cancer (NMIBC). The risk of recurrence and progression of NMIBC after the first TURB varies from 48-70% and 7-40%, respectively . It is crucial to determine the risk of recurrence and progression to muscle-invasive disease in the short and medium term. This stratification is determined at the diagnosis, and tumors may be classified into four risk groups: low, intermediate, high, and very high, following the system developed by the European Association of Urology (EAU) (www.nmibc.net; accessed on 15 November 2022). This system includes different variables such as age; if the tumor is de novo or recurrent; its size and numbers; associated carcinoma in situ; the pathological stage according to the TNM classification; and the differentiation degree (low-grade or high-grade) . The treatment of low-risk NMIBC varies from different agents, and nowadays, Mitomycin C is widely used in low-grade tumors. On the other hand, Bacillus Calmette-Guerin (BCG) is the treatment of choice for high-grade NMIBC; therefore, both treatments are standard of care. The interaction of cancer with the immune system promotes the recruitment and activation of different myeloid and lymphoid cell populations, as shown by infiltrates of macrophages, dendritic cells, mast cells, granulocytes, and lymphoid cells found in immunopathological studies . The immune system plays an efficient role in limiting cancer progression at early stages; however, one or more cancer cell variants may survive this initial phase, leading to a dynamic equilibrium wherein tumor-specific lymphocytes exert continuous selective pressure over cancer cell variants. Finally, tumors may develop different immunoevasive mechanisms to escape immune response, which leads to overt tumor development and may modulate cancer response to therapy. There is an increasing interest in studying the precise mechanisms by which immune cells promote cancer cell death and response to different drugs. Previous data suggest that, in patients with bladder cancer, the content of immune cells in urine is similar to that in the tumor microenvironment, but this issue needs further clarification . On the other hand, although lymphoid infiltrates in some types of melanomas, colorectal, and breast cancers predict a better prognosis , this issue has not been studied in detail in bladder cancer. Hence, to our knowledge, no previous studies describe lymphoid populations in these tumors and their correlation with peripheral blood and healthy bladder tissue. We present here a descriptive study conducted in a population of 41 patients with NMIBC, in which immune cell subpopulations from tumor tissue, adjacent healthy bladder, and peripheral blood have been analyzed. We show the differential distribution of immune cell subsets among the different tissues and provide preliminary evidence for biomarkers predictive of patient outcomes in peripheral blood. 2. Materials and Methods 2.1. Study Population This descriptive study was performed in the period between February 2019 and January 2022. Samples from peripheral blood, urothelial bladder cancer and adjacent healthy urothelial tissue (confirmed by a Pathologist) were collected from 41 patients treated at the Department of Urology of La Princesa University Hospital, Madrid, Spain. The epidemiological and clinical characteristics of these individuals are detailed in Table 1. Patients were divided into high-grade urothelial bladder cancer according to WHO/ISUP TNM 8th edition. In order to achieve a more homogeneous sample, we only collected urothelial pTa and pT1 bladder carcinoma samples, excluding CIS, muscle-invasive, and other pathological differentiation-containing samples. Recurrences were identified in cystoscopies performed during patient follow-up. Tumor size was determined by comparing the tumor with the resection loop (2.5 cm long) during surgery. Tissue samples were collected in the operation room (OR) and kept at 4 degC until their processing. 2.2. Sample Processing Blood and bladder samples (both urothelial bladder cancer and normal bladder urothelium were processed in the laboratory as follows: After disaggregation of fresh samples from tumors and normal bladder urothelium with a razor blade and subsequent filtration through a 40 mm-pore cell strainer (Falcon), mononuclear cells were isolated using a density gradient centrifugation (Ficoll-Paque; Pan-Biotech). Peripheral blood mononuclear cells (PBMC) were isolated as follows: peripheral blood collected in EDTA-treated tubes was diluted 1:1 with PBS and carefully added to Ficoll-Paque (Pan-Biotech; proportion 4:3) in order to avoid mixing. After centrifugation (400x g, 30 min, without brake), PBMC-containing interphase was collected with a pipette, transferred to a new tube and washed twice with PBS. Finally, isolated cells were cryopreserved in media containing 90% fetal bovine serum (FBS; HyClone TM) and 10% DMSO (Inilab) until analysis. 2.3. Flow Cytometry Analysis Mononuclear cells from blood and tissues were incubated with Human FcR blocking reagent for 10 min at room temperature and then labeled with the different antibodies for 30 min at 4 degC. Finally, the cells were washed and resuspended in 200 mL PBS 1x. The antibodies were distributed in the following panels:Panel 1 (T lymphocytes 1): CD49b, CD127, CD3, LAG3, CD4, CD25 and CD8; Panel 2 (T lymphocytes 2): TIM3, PD1, CD3, ICOS, CD27, CD4 and CD8; Panel 3 (myeloid cells): MHCII, CD 127a/b (SIRP), IDO1, CD14, CD11c and CD123; Panel 4 (NK cells): KIR, NKG2a, NKG2d and CD56. Fluorochromes and providing Companies are listed in Supplementary Table S1. Samples were acquired using a FACSCanto II flow cytometer (BD Biosciences), and data obtained were subsequently analyzed with FlowJo software (BD Biosciences). 2.4. Statistical Analysis Quantitative variables obtained by flow cytometry were represented in bar graphs as mean +- standard deviation (SD) or in box-and-whiskers plots. Analysis of variance was performed to determine differences in cell subsets between blood and tissues (tumor and normal bladder urothelium), and Sidak's multiple comparison post-test was used. For correlation analyses, Spearman's coefficient r was calculated. Differences between the 2 groups (Ta vs. T1, relapse vs. non-relapse, and low grade vs. high grade) were determined using an unpaired t-test. We used a multivariable logistic regression model to assess the association of the expression of molecules in the different leukocyte populations with TNM independently of known risk factors (e.g., differentiation and tumor size). Variables included in the model were those found to be statistically significant, with p < 0.1 in the univariable analysis. Data analyses were performed using Graph Pad Prism 8 Software (GraphPad Software, San Diego, CA, USA, www.graphpad.com, accessed on 15 November 2022) and Graph Stata (StataCorp, College Station, TX, USA). 2.5. Ethical Approval The study has been approved by the institutional review board and ethics committee at La Princesa University Hospital (IRB00005840; register number 4709). It meets international standards of data protection and is in line with practice guidelines established in the Declaration of Helsinki. Informed consent was signed by all the patients before surgery. 3. Results 3.1. Differential Immune Profile in Samples from Patients with Urothelial Bladder Cancer In order to carry out a detailed characterization of immune cell populations involved in anti-tumor response to urothelial bladder cancer, we analyzed by flow cytometry the percentage of different immune cell subsets in peripheral blood, healthy bladder tissue and tumor samples from a cohort of 41 patients (Table 1). When comparing peripheral blood and tumor infiltrate , we found a significant increase of CD4+ lymphocytes and monocytes in peripheral blood, while the percentage of CD8+ T lymphocytes and myeloid-derived suppressor cells (MDSCs) was significantly higher in tumors. Further analysis of specific exhaustion-related markers within these populations showed a significant increase of CD4+ CD127+ lymphocytes, CD4+ CD27+ lymphocytes, CD123+ monocytes, IDO+ monocytes and SIRP+ monocytes in peripheral blood. Conversely, higher percentages of CD8+ CD127+ lymphocytes, CD8+ LAG3+ lymphocytes, CD8+ PD-1+ lymphocytes and IDO+ MDSCs were found in tumor samples. Comparative analysis of samples from peripheral blood and healthy bladder tissue showed higher amounts of total CD4+ lymphocytes, CD4+ CD127+ lymphocytes and CD4+ CD27+ lymphocytes in the blood, while increased percentages of total CD8+, CD8+ CD49b+, CD8+ CD127+, CD8+ LAG3+, CD8+ CD27+, CD8+ PD-1+ and CD8+ TIM3+ lymphocytes were detected in the bladder. Finally, only a significant increase in bladder total monocytes was found when comparing bladder and tumor samples . We next determined the expression levels of different surface markers present in immune subpopulations by quantifying their mean fluorescence intensity (MFI) in flow cytometry analyses. When comparing peripheral blood and tumor samples, significantly higher expression of CD127 and LAG3 within CD8+ lymphocytes, and increased IDO within MDSCs, were found in the tumors. On the other hand, higher levels of SIRP in monocytes were identified in peripheral blood . Furthermore, a strong significant correlation was observed in CD127 MFI (r = 0.82; p < 0.0001) and in LAG3 MFI (r = 0.76; p < 0.0001) of CD8+ lymphocytes between tumor and peripheral blood. Likewise, a significant correlation was found in monocyte SIRP MFI (r = 0.49; p = 0.017) between both samples. Furthermore, when considering healthy bladder and peripheral blood, we detected significantly increased expression of LAG3 in CD4+, CD127, and LAG3 in CD8+ bladder lymphocytes. Similarly, the expression of IDO in both monocytes and MDSCs was higher in bladder tissue. Only SIRP expression in monocytes was significantly lower in bladder samples than in blood . Interestingly, when comparing bladder tissue and tumor samples, increased levels of LAG3 were seen in CD4+ lymphocytes, CD8 and CD127 in CD8+ lymphocytes, as well as SIRP within the monocyte population was found in the bladder . 3.2. Immune Markers in Tumor Progression and Patient Outcome In view of the differences observed in the immune profile among samples, we sought to investigate the differential expression of immune markers in relation to parameters of tumor evolution and patient outcome (i.e., relapse appearance, TNM--pTa/pT1 -, differentiation -low/high tumor size--</> 3 cm -). As shown in Figure 3A, a higher percentage of CD4+ TIM3+ cells were detected in the peripheral blood of patients that do not present relapse. In addition, monocytes in peripheral blood from patients with pTa tumors showed lower IDO levels than those of patients that bear pT1 tumors . Likewise, the percentage of different immune cell subsets in bladder and tumor samples showed significant differences in patients with and without relapse, tumors with low and high histological grade, and pTa/pT1 tumors. These cell populations are detailed in Figure 3B. 3.3. CD4+ CD27+ Cells and IDO+ Monocytes Are Independent Markers for Tumor Progression In order to determine whether previously analyzed immune markers could be used as independent markers for tumor progression or patient outcome, a multivariable logistic regression analysis was performed considering relevant variables such as histological grade and tumor size. This analysis showed that the percentage of CD4+ CD27+ cells and IDO+ monocytes remained independent predictors of tumor progression . This model, which combines immune parameters of patient peripheral blood with histological grade and tumor size, discriminates pTa and pT1 tumors with a sensitivity of 75%, a specificity of 96.65%, a positive predictive value of 90%, and a negative predictive value of 88% (area under ROC curve is 0.9783) . 4. Discussion Many studies characterize different aspects of anti-tumor immune response in various types of cancer. Thus, in non-small cell lung cancer, a higher density of CD8+ tumor infiltrate lymphocytes (TILs) may promote immune response at the level of the tumor microenvironment . Likewise, a study in patients with metastatic colon cancer determined the presence of CD8+ population densities and T lymphocyte infiltrates through immunohistochemistry in samples from metastatic lesions (lung and liver), demonstrating the prognostic significance of the existence of CD8+ in these tumors . On the other hand, myeloid-derived suppressor cells (MDSC) have been detected in the blood of patients with glioblastomas and other tumors, with a significant increase in the early and advanced stages of the disease . Increasing data support the immunosuppressive role of this group of cells through their interaction with adaptive and innate immunity, as well as through stimulation of angiogenesis. Chronic stimulation of T cells by tumor antigens leads to a process of lymphocyte exhaustion, accompanied by increased surface LAG3 and PD1 levels . LAG3 reduces T cell proliferation, decreases the secretion of specific cytokines, and contributes to regulatory T cell-mediated immune suppression . The presence of LAG3 in TILs from ovarian cancer has been previously reported . Little is known about the role of CD8+ CD127+ lymphocytes, although their presence in follicular lymphoma may have a favorable prognostic role by effectively promoting the immune response in the tumor . Most of the current evidence on the immune response to bladder cancer focuses on murine tumor models, on determining global lymphoid populations through immunohistochemistry in tissue, or on studying immune profiles in urine in patient samples. Some studies performed by immunohistochemistry techniques have demonstrated that high levels of dendritic cell infiltrates were associated with a worse response to BCG . Similarly, both low CD8+/MDSC and CD8+/TReg ratios are related to poorer outcomes in bladder cancer . Likewise, patients with high levels of CD8+ exhaustion markers have a higher risk of recurrence after BCG . A recently published study analyzes different lymphocyte populations in urine before and after BCG treatment by mass cytometry, establishing possible markers of response and selection of therapy in patients with NMIBC . Our study presents for the first time a detailed analysis by flow cytometry of the immune infiltration profile in tumor tissue and its correlation with healthy bladder tissue and peripheral blood in patients with NMIBC. Due to the high prevalence and recurrence rate of NMIBC, we have focused primarily on this entity independently of muscle-invasive cancers. Likewise, we have not included CIS-containing NMIBC samples because the coexistence of CIS radically modifies the prognosis of the disease. However, in view of the results obtained and the statistically significant differences achieved in NMIBC, it will be of great interest to extend the study to T2 and CIS. We have found differences in specific immune subsets and differentially expressed markers between peripheral blood and tumor, while similar changes can be observed between peripheral blood and normal bladder urothelium. Interestingly, CD127 and LAG3 expression in CD8+ lymphocytes, and SIRP expression in monocytes, show a correlation between tumor samples and blood, indicating that peripheral expression of these parameters reliably reflects the composition of tumor infiltrate. Of note, few significant differences are found when comparing tumor and healthy bladder . Particularly striking is the fact that, in patients with high-grade tumors, an increase in populations with immunosuppressive characteristics (IDO+ and SIRP+ monocytes) is observed in the healthy bladder in contrast to tumor tissue . These findings highlight the relevance of bladder immune response in the pathogenesis of NMIBC and support the hypothesis that bladder cancer is a pan-urothelial disease. In our univariable analysis, we observed a significant increase in the percentage of CD4+ TIM3+ in the peripheral blood of patients who have not relapsed. Similarly, we have observed increased CD8+ lymphocytes expressing TIM3 and PD1 exhaustion-related markers in normal bladder urothelium from non-relapsed patients . The expression of PD-1 and TIM3 has been described in exhausted CD4+ and CD8+ lymphocytes; however, activated T lymphocytes up-regulate PD-1 expression, and some subpopulations of activated CD4+ also express TIM3 . Therefore, further studies with a larger number of patients are needed to determine the functional role of these immune cells in NMIBC and confirm their predictive role of low probability of relapse. The identification of a marker of tumor evolution in peripheral blood will be of special relevance to improve patient monitoring through non-invasive procedures. We have obtained a predictive model for TNM which combines peripheral blood parameters (% CD27+ CD4+ lymphocytes, % IDO+ monocytes, LAG3 MFI in CD4+ lymphocytes) with histological grade and tumor size and discriminates pTa and pT1 tumors with a sensitivity of 75% and specificity of 96.65%. This model may help to reliably stratify patients with NMIBC in uncertain cases as an extra tool for patient follow-up and management. As a limitation of our study, we have not assessed the presence of lymphovascular invasion that may affect tumor-peripheral blood recirculation of immune cells since Pathologists in our hospital only describe the presence or absence of lymphovascular invasion in radical cystectomy but not in transurethral resection samples. Another limitation is that we have conducted a descriptive study, not focused on monitoring the immune response throughout the natural progression of cancer. Therefore, we have not detected any patients with progression. This is an essential aspect that will be addressed in future research. 5. Conclusions Determining the immune marker profile in peripheral blood and tissue may provide relevant information on tumor pathogenesis and have diagnostic and prognostic implications in NMIBC. In this regard, we have detected an increase in populations with immunosuppressive characteristics in the healthy bladder of patients with high-grade tumors. These findings highlight the relevance of bladder immune response in the pathogenesis of NMIBC and support the hypothesis that bladder cancer is a pan-urothelial disease. In addition, in a highly prevalent disease like NMIBC, this type of study is of paramount importance since it can provide early information about the immune response in the tumor microenvironment. The use of a panel of antibodies to assess immune populations in peripheral blood by flow cytometry is feasible, minimally invasive and reproducible in clinical practice. Therefore, it may facilitate better follow-up and decision-making in the diagnosis and treatment of these patients. Despite the heterogeneity in the study population, we still observe significant differences among diverse immune parameters and provide preliminary predictive models that may help to stratify patients. Thus, our findings set the basis for further analyses of immune cell subsets in specific scenarios of NMIBC, which allow us to reliably identify biomarkers and establish predictive models of disease progression. Acknowledgments A special acknowledgment to the Head of the Department of Immunology, F. Sanchez Madrid, for his support. Supplementary Materials The following supporting information can be downloaded at: Supplementary Table S1: Antibodies and fluorochromes. Click here for additional data file. Author Contributions Conceptualization, E.A.A. and C.O.G.; methodology, M.A.C., G.C.L. and E.A.A.; formal analysis, G.C.L., E.A.A., A.A. and H.d.l.F.; investigation, G.C.L., E.A.A.; resources, A.A., N.R.-L. and C.O.G.; writing--original draft preparation, G.C.L., E.A.A., C.V.B. and A.A.; writing--review and editing, H.d.l.F., N.R.-L., A.A. and C.O.G.; funding acquisition, A.A. and C.O.G. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of University Hospital La Princesa (IRB00005840; code: 4709) for studies involving humans. Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement The data presented in this study are available on request from the corresponding author. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Markers differentially expressed in samples from patients with urothelial bladder cancer. (A) Graphics show differentially expressed surface molecules in CD4+ lymphocytes, CD8+ lymphocytes, and monocytes from patient tumor samples and peripheral blood. (B) Differentially expressed surface molecules in CD4+ lymphocytes, CD8+ lymphocytes, and monocytes from patient bladder tissue and peripheral blood. (C) Differentially expressed markers in monocytes from patient bladder tissue and tumor samples. In all cases, only statistically significant results (Mean + SD of % positive cells) are shown; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. MDSC, myeloid-derived suppressor cells. Figure 2 Markers with differential levels of expression in samples from patients with urothelial bladder carcinoma. (A) Graphics show the mean fluorescence intensity (MFI) of surface molecules expressed in CD8+ lymphocytes and myeloid cells from patient tumor samples and peripheral blood. (B) Graphics show the MFI of surface molecules expressed in CD4+ lymphocytes, CD8+ lymphocytes and myeloid cells from patient bladder tissue and peripheral blood. (C) Graphics show the MFI of surface molecules expressed in CD4+ lymphocytes, CD8+ lymphocytes and myeloid cells from patient bladder tissue and tumor samples. In all cases, only statistically significant results (Mean + SD of MFI) are shown; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. MDSC, myeloid-derived suppressor cells. Figure 3 Analysis of immune markers for tumor evolution and patient outcome. (A) Graphics show the percentage of CD4+ TIM3+ lymphocytes in the peripheral blood of individuals with Non-relapse vs. Relapse (left) and the percentage of monocytes IDO+ in the peripheral blood of individuals with pTa vs. pT1 (right). Statistical significance is shown (p). (B) Table showing the statistically significant results of the univariable analysis to compare individuals with either Non-relapse/Relapse, Low grade/High-grade tumors, and pTa/pT1 tumors. Values correspond to mean +- SD, * student t-test. Figure 4 Multivariable analysis. (A) Table showing multivariable logistic regression to compare individuals with pTa and individuals with pT1 tumors. All covariates with a p-value < 0.1 in the univariable analysis were considered. (B) ROC curve showing the ability of the parameters shown in (A). to discriminate between patients bearing pTa and pT1 tumors. Sensitivity 75.00%, specificity 95.65%, positive predictive value, 90.00%, and negative predictive value, 88.00%. cancers-15-01364-t001_Table 1 Table 1 Demographic and clinical characteristics of the study population. Patients n 41 Sex Female 11 (25.9%) Male 39 (73.1%) Age Mean +- SD: 74.97 +- 38.89 (39-94) WHO/ISUP TNM 8th edition pTa 27 (65.8%) pT1 14 (34.2%) High grade 25 (60.9%) Low grade 16 (39.1%) Recurrences at 4 years Yes 5 (12.2%) (22, 6, 11, 5 and 4 months after diagnosis) No 36 (87.8%) Tumor Size >=3 cm: 13 (31.7%) <3 cm: 28 (68.3%) Risk factor: tobacco Smokers: 7 (17%) Nonsmokers: 12 (29.4%) Ex-smokers: 22 (53.6%) Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000244 | Understanding the distribution of dogs in the environment is relevant for establishing human and animal health actions. In the present study, we analyzed the influence of community feeders and commercial food outlets on the spatial distribution of free-roaming dogs in an urban area of a municipality in Southeast Brazil. The dogs were identified via photographic capture and recapture performed over five sampling efforts. The spatial densities of dogs were determined using the Kernel method. Spatial correlations between the distribution of free-roaming dogs and the locations of community feeders and commercial food outlets were analyzed using the K function. During the study, 1207 captures/recaptures were performed encompassing 554 dogs, the majority (62.6%) of which were males. Agglomerations of male and female dogs were observed in the areas where food was present. Positive spatial autocorrelations were detected between the distribution of dogs and food sources. The median distances between dogs and community feeders or commercial food outlets were 1.2 and 1.4 km, respectively, and the difference between these two was statistically significant. The presence of community feeders and food outlets demonstrates the influence of human activity, on the spatial distribution of free-roaming dogs. These results will be useful for developing strategies aimed at the improvement of animal welfare and the prevention of zoonoses. photographic captures stray dogs ecology and behavior animal welfare Fundacao de Amparo a Pesquisa do Estado de Minas GeraisAPQ-02612-16 Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior001 This study was supported by the Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG; grant number APQ-02612-16) and partially funded by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; grant code 001). pmc1. Introduction In Brazil, dogs are part of the urban ecosystem in both small country towns and large city conurbations . The canine population within the country is estimated to number around 54.2 million animals , with a large proportion being free-roaming dogs that roam the streets freely without the direct supervision of humans . Although dogs provide numerous benefits to humans, such as companionship, stress reduction, physical activity, improved mental health, assistance for people with disabilities, protection, and safety, free-roaming animals cause accidents and spread infectious diseases . Moreover, such free-roaming dogs may have a shorter lifespan in comparison with domiciled animals , considering that the former receive minimal or no veterinary care and have limited access to adequate nutrition. For these reasons, the management of free-roaming dog populations is gaining increased research attention and is considered a relevant issue from the viewpoint of public health and animal welfare . While interactions between restricted dogs and humans exhibit many different forms , the density of the free-roaming canine population tends to increase concurrently with that of the human population. The maintenance of these animals in urban environments depends on direct sources of food and support (community feeders), and on indirect sources such as commercial food outlets (stores and restaurants) and garbage collection points . The availability of food influences the spatial distribution of dogs, while the search for food motivates them to travel longer distances within their environs . The population dynamics of free-roaming dogs are influenced substantially by the supply of food by householders since a small number of community feeders can support a large canine population . Despite its likely relevance to the ecology and spatial distribution of free-roaming dogs within the environment, the direct supply of food by the human population has been poorly analyzed in the literature. A better understanding of this issue may be pertinent for population control, improvement of animal welfare and the prevention of zoonoses . In a study carried out previously in the same area as the present work, agglomerations of unrestricted dogs were identified in places close to food stores . This study extends the investigation of the influence of the human community on the ecology of the canine population. In the present investigation, we set out to analyze the influence of community feeders and commercial food outlets on the ecology and spatial distribution of free-roaming canine populations in an urban setting by carrying out photographic captures and recaptures. 2. Materials and Methods 2.1. Site of Study The investigation was performed in Divinopolis, the largest municipality in the mid-west of the state of Minas Gerais, Brazil, with a population of approximately 242,505 inhabitants . The specific study site encompassed eight neighborhoods in the municipality comprising some 7600 residents . 2.2. Data Collection Photographic captures and recaptures of free-roaming dogs (defined as animals roaming the streets not accompanied by an owner) were performed over five sampling efforts (campaigns) conducted between September 2018 and September 2019 inclusive. Samplings were carried out in the mornings of three consecutive days during the first two weeks of the month and were repeated every three months. The vehicle used during each sampling always followed the same route and covered all of the streets in the designated areas at a speed of 20 km h-1. The team comprised the driver together with two researchers who were responsible for photographing and recording the general characteristics of the photographed animals, including size, color, natural marks and sex, all of which were useful for later identification. A Canon PowerShot SX60HS camera was used to photograph the dogs at a maximum distance of 10 m in order to obtain good-quality pictures while taking care not to frighten the animals away. At least three photographs of each dog were taken from different positions. The geographical coordinates of each capture/recapture point (the place where the dog was sighted) were recorded together with those of community feeders (food such as dry dog food and food scraps provided by households either in containers or directly on the ground) and commercial food outlets (fast-foods, grocery stores, bars, restaurants, bakeries, butchers and food markets). Data concerning dogs captured during the three days of sampling were aggregated in order to assemble the database from the five campaigns. The aggregation of data in campaigns was defined to increase the robustness and power of comparisons and, as well as to compare our results with that of past literature. Dogs that had been photographed in one campaign but captured again in a new campaign were considered recaptured. Each animal received an identification code and its details (pictures, description and position) were recorded in a spreadsheet. Data were analyzed and classified independently by two researchers. Using the Kappa index, a high (0.86) and significant (p < 0.01) agreement was recorded between them in identifying the 1207 photocaptures. Any discrepancies were resolved by consensus. Finally, a database was created containing information about all of the dogs captured and/or recaptured during the five campaigns. 2.3. Statistical Analysis The nearest-neighbor distance approach was used to identify the existence of regions with agglomerations of dogs in the study area . Kernel maps were prepared for the entire study period, and separately for each capture/recapture event, and stratified by sex of the dogs. The search radius was set at 100 m and the quantile normalization method was adopted as the most appropriate statistical tool for visualization of the different concentrations of dogs in the geographic space . Possible spatial correlations between the distribution of free-roaming dogs and the locations of community feeders and commercial food outlets were investigated using Ripley's bivariate K function . The linear distance matrix function was used to estimate the distances of the meeting points of the dogs in relation to the community feeders and commercial food outlets, with the values expressed as medians and interquartile ranges (IQR). Median distances were compared using the Mann-Whitney test with the significance level set at 5%. Spatial analyses were performed using QGIS software version 3.16.16 while statistical analyses were carried out with the aid of R software version 4.2.0. 3. Results A total of 1207 photographic captures/recaptures involving 554 different free-roaming dogs were accomplished during the study period (September 2018 and September 2019 inclusive). The proportion of captured free-roaming male dogs was typically twice that of females, with a similar profile observed for recaptured dogs. (Table 1). Most dogs in all campaigns were small, as compared to medium and large animals. In addition, black dogs were predominant (Table 2). The number of dogs captured for the first time decreased as capture efforts progressed. The number of recaptured individuals tended to increase over the study period, although there was a decrease in the last effort. . The numbers of community feeders and commercial food outlets increased slightly from the first to the third sampling effort but decreased thereafter. There were more community feeders than commercial food outlets (Table 3). According to nearest neighbor distance analysis, the animals were distributed in a clustered manner, that is, they were not randomly distributed in geographic space. The distribution patterns of agglomeration were statistically significant (p < 0.01). As shown by the Kernel map , animal clusters were located in the vicinity of community feeders and food outlets. Although the sites of food sources varied over the study period, canine agglomerations always remained close to these locations regardless of the sex of the animals . The K function revealed the existence of positive spatial autocorrelations up to 500 m between the distribution of free-roaming dogs and food sources . The median distance between dogs and community feeders was 1.2 km (IQR = 0.5-2.6 km), whereas the median distance between dogs and commercial food outlets was significantly higher at 1.4 km (IQR = 0.5-2.7 km; p < 0.01). 4. Discussion The results demonstrate that the interaction between humans and dogs plays a relevant role in the distribution of the animals in the study area with the occurrence of clusters being positively correlated with the presence of food sources, particularly community feeders. The greater number of male dogs and the agglomeration of males and females in the vicinity of food outlets in the study area has been established previously by Melo et al. (2020) with distance values similar to those reported herein. The predominance of males occurs due to behavioral factors of the dogs and cultural aspects related to the care of animals in the region . The consistency of the results related to the agglomeration may be explained by the absence of interventions aimed at the dispersion of the animals and the lack of control of the free-roaming canine population . In addition, the number of new free-roaming dogs captured decreased as the number of dogs recaptured increased. The existence of new free-roaming dogs (captured) in the region after a year of continuous captures, may demonstrate the lack of responsible custody by owners (canine abandonment or escape) and, to a lesser extent, the existence of canine reproduction . The novel finding of dog clusters in areas close to community feeders reinforces the significance of human-dog interactions in the maintenance of free-roaming dogs in urban settings. It is of note that during the study, a small number of dog clusters were observed in locations that had no feeders or food outlets. This finding can be explained by the behavior of some guardians who allow free access of their domiciled dogs to the streets and even feed them outside their properties . Such results show that in the absence of interventions that consider the responsible ownership of animals and the home ranges of dogs, there will be no reduction in the stray dog population. Dogs, unlike wolves from which they evolved, depend primarily on humans for food . Thus, direct support by community feeders through the provision of both food and care for the free-roaming animals favors the continuation and augmentation of the free-roaming canine population in the urban environment . Thus, human support is essential for understanding the ecology of unrestrained dogs in urban environments. Families who regularly feed free-roaming dogs are responsible for sustaining these animals, so only a small fraction of households can accommodate large, tolerant, unrestrained dogs . In the present study, free-roaming dogs gathered together closer to community feeders than to food outlets. Most of the time there were no humans near the feeders, a situation that contrasts with that established for food outlets. Kittisiam et al. (2021) analyzed the contact network of free-roaming dogs in a university campus in Thailand and demonstrated that the average number of contacts for the weekend network was significantly higher than that for the weekday network, indicating that dogs tended to cluster more intensely in the absence of humans. Our study showed that community feeders might be more advantageous to the animals than food outlets because they afford a continuous and possibly more stable nutritional source. As part of an educational project ('Projeto AlimentaCao') aimed at alerting schoolchildren to the problem of abandonment of domestic animals, and installed feeders at points on the campus of the Universidade Tecnolologica Federal do Parana that were some distance away from the university restaurant. These researchers reported that the number of free-roaming dogs that congregated in the surroundings of the restaurant diminished whilst the population using the feeder points stabilized and became healthier and more docile. An alternative approach of restricting the amount of food would also be effective in controlling a population of free-roaming dogs at a particular location . However, such a measure would be ethically questionable and would simply lead to the dispersion of animals as they move to new areas in search of food . The more advantageous solution would be to relocate community feeders to defined areas with less movement of people and vehicles. Although the control of dog habitats and their ranges may not result in a decrease in the canine population, it may be effective in reducing accidents, the transmission of diseases, bites and pollution in busier locations. The availability of food resources was constant throughout the period of the present study, a situation that may be representative of different areas of Brazil and of other parts of the world. In India, for example, 37% of individuals reportedly feed free-roaming dogs . Feeding free-roaming dogs can create and strengthen the bonds between humans and dogs , and allow the animals to move, socialize and express their natural behavior . On the other hand, the support offered by community feeders can also be considered a public health problem because it sustains canine populations that act as reservoirs of zoonotic diseases , cause accidents and pollute the environment. Moreover, from the viewpoint of animal welfare, the quality of life and the longevity of free-roaming dogs tend to be inferior to those of domiciled animals . While various studies support the thesis that the search for food is a key factor in determining canine mobility and agglomeration , it should be noted that other factors influence the distribution of free-roaming dogs in urban areas including the growth of cities, climate, reproductive status and the search for partners . Therefore, controlling the habitat and movement of free-roaming dogs is a challenging task that must be adopted together with other strategies. Sterilization can contribute to the reduction in birth rates, but in the region of the present study, the abandonment of dogs is the main reason for the increase in the unrestricted population . In order to reduce or eliminate the population of free-roaming dogs, it will be necessary to adopt broad and effective measures of responsible animal guardianship, which may be difficult to implement in the short term depending on the socioeconomic and cultural contexts . In this sense, the provision of food and the management of appropriate care may be relevant actions. Installing feeders in favorable environments can reduce the risk of accidents and bites, minimize the risk of disease transmission and improve animal welfare . In addition, if combined with other actions such as vaccination, disease prevention and installation of shelters, the provision of feeders would certainly improve the quality of life of the animals . However, it is important to emphasize that such measures are palliative and that the problems associated with free-roaming dogs will only be solved through the awareness and accountability of guardians concerning the social and economic consequences caused by the abandonment of their animal companions , along with the implementation of responsible adoption policies . Strategies to estimate animal populations share as basic principles, uncertainties regarding the detection of all individuals that pertain to the target population in a given area and heterogeneities in the individual encounter probabilities . The validity of the methods based on counting or the capture and recapture of dogs is only achieved when the animals are correctly identified in all capture activities . Obtaining accurate information about free-roaming dogs can be a challenging process, and inadequate methods can result in biased information . Among the various methods for estimating population, photographic capture and recapture is advantageous because it is a safe, fast, and cost-effective option. Animals do not need to be physically captured, reducing their exposure to risks and adverse effects. Moreover, the photographic capture technique enables the individual identification of animals based on natural markings, and analysis of the previous capture history can determine whether an animal has been recaptured . Combining this method with the Geographical Coordinate System (GPS) to record the location of free-roaming dogs allows for expanded analysis and a better understanding of the ecology of unrestricted dogs in urban areas . On the other hand, the low quality and lack of detail in the photograph can make the process of identifying the dog more difficult. However, in the present study, the comparison of photos by independent researchers, combined with quality training, can optimize the identification process. The present study was subject to some limitations that are intrinsic to the photographic capture method. The majority of free-roaming dogs move around, which makes it difficult to photograph them, and this may give rise to the loss of some information. However, during the search process, all streets in the study area were covered and this minimized sample deficiencies because when a dog could not be found in one street, it was almost certain that it could be found in another. An additional limitation was that the sampling efforts took place only in the morning and not throughout the day. However, dogs are more active in the morning and tend to rest as the temperature rises ; therefore, sampling efforts were focused in the period of highest activity. 5. Conclusions Agglomerations of free-roaming dogs were positively associated with the locations of commercial food outlets and, more especially, with those of community feeders. The provision of food by community feeders was essential in maintaining the concentration of dogs in the vicinity of food sources. The results obtained not only add to our understanding of the ecology and behavior of free-roaming dogs in urban areas but also highlight the need for policies to reduce the risks associated with the presence of free-roaming animals. Moreover, appropriate management of food and water resources should be implemented in order to improve the quality of life of these animals such as the allocation of specific and supervised points far from busy roads and residential/commercial areas. We hope that the outlined recommendations can help improve future interventions by providing more appropriate strategies. Additionally, we suggest that the spatial distribution of free-roaming dogs be more widely studied in the literature, especially through intervention studies, assessments in urban and rural areas, and evaluations of residents' perceptions of supporting these animals. Supplementary Materials The following supporting information can be downloaded at: Figure S1: Clusters of free-roaming dogs and sites of community feeders and commercial food outlets during in each of the five sampling efforts out in an urban area located in Divinopolis, Minas Gerais, Brazil; Figure S2: Clusters of free-roaming dogs and sites of community feeders and commercial food outlets stratified by sex in each of the five sampling efforts out in an urban area located in Divinopolis, Minas Gerais, Brazil; Data presented in this study. Click here for additional data file. Author Contributions Conceptualization, S.N.d.M., V.S.B., E.S.d.S., M.A.P.H., R.G.T.-N., P.H.A.S., A.K.R.C., R.A.N.R., C.M.d.S.G., F.D.S.M.; methodology, S.N.d.M. and V.S.B.; validation, S.N.d.M. and V.S.B.; formal analysis, S.N.d.M., V.S.B., E.S.d.S., M.A.P.H., R.G.T.-N., P.H.A.S., A.K.R.C., R.A.N.R., C.M.d.S.G., F.D.S.M.; investigation, S.N.d.M., V.S.B., E.S.d.S., M.A.P.H., R.G.T.-N., P.H.A.S., A.K.R.C., R.A.N.R., C.M.d.S.G., F.D.S.M.; writing--original draft preparation, S.N.d.M., V.S.B., E.S.d.S., M.A.P.H., R.G.T.-N., P.H.A.S., A.K.R.C., R.A.N.R., C.M.d.S.G., F.D.S.M.; writing--review and editing, S.N.d.M., V.S.B., E.S.d.S., M.A.P.H., R.G.T.-N., P.H.A.S., A.K.R.C., R.A.N.R., C.M.d.S.G., F.D.S.M.; supervision, S.N.d.M. and V.S.B.; project administration, S.N.d.M.; funding acquisition, V.S.B. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement The study project was submitted to and approved by the Animal Research Ethics Committee of the Universidade Federal de Sao Joao del Rei (UFSJ, Sao Joao del Rei, MG, Brazil; protocol no. 014/2016). All procedures followed the ethical guidelines for the use of animals in research as issued by the Conselho Nacional de Controle de Experimentacao Animal. Informed Consent Statement Not applicable. Data Availability Statement The data presented in this study are available in the Supplementary Material of this study. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Temporal evolution in the number of free-roaming dogs captured/recaptured during the five sampling efforts carried out in an urban area located in Divinopolis, Minas Gerais, Brazil. Figure 2 Clusters of free-roaming dogs and sites of community feeders and commercial food outlets in an urban area located in Divinopolis, Minas Gerais, Brazil. Figure 3 The positive spatial autocorrelations between the distribution of free-roaming dogs and (A) commercial food outlets, (B) community feeders and (C) community feeders + commercial food outlets, showing the theoretical Poisson K-function (dashed red line), the envelope of confidence (gray band) and the observed K function (solid black line). animals-13-00824-t001_Table 1 Table 1 Number of free-roaming dogs captured/recaptured during the five sampling efforts carried out in an urban area located in Divinopolis, Minas Gerais, Brazil. Animals Sampling Efforts 1st 2nd 3rd 4th 5th Total Captured dogs [n (%)] Males 111 (62.3) 71 (70.3) 77 (62.0) 51 (54.3) 37 (65.0) 347 (62.6) Females 63 (35.4) 27 (26.7) 38 (30.7) 40 (42.5) 18 (31.5) 186 (33.6) Undetermined 4 (2.3) 3 (3.0) 9 (7.3) 3 (3.2) 2 (3.5) 21 (3.8) Total 178 101 124 94 57 554 Recaptured dogs [n (%)] Males - 41 (69.5) 50 (70.4) 55 (67.9) 55 (67.9) 279 (64.7) Females - 18 (30.5) 20 (28.2) 32 (36.4) 25 (30.9) 142 (33.0) Undetermined - 0 (0) 1 (1.4) 2 (2.2) 1 (1.2) 9 (2.2) Total - 59 71 88 81 431 animals-13-00824-t002_Table 2 Table 2 Characteristics of free-roaming dogs captured during the five sampling efforts carried out in an urban area located in Divinopolis, Minas Gerais, Brazil. Sampling Efforts Captured Dogs [n (%)] 1st 2nd 3rd 4th 5th Total Size Small 98 (54.7) 55 (54.5) 70 (56.5) 66 (70.2) 31 (54.4) 320 (57.7) Medium 41 (23.0) 25 (24.8) 26 (21.0) 13 (13.8) 16 (28.1) 121 (21.8) Big 39 (22.3) 21 (20.7) 28 (22.5) 15 (16.0) 10 (17.5) 113 (20.5) Total 178 101 124 94 57 554 Color Yellow 25 (14.0) 10 (9.9) 6 (4.8) 3 (3.2) 4 (7.0) 48 (8.6) White 35 (19.6) 18 (17.8) 26 (21.0) 17 (18.1) 11 (19.3) 107 (19.3) Gray 2 (1.1) 0 (0.0) 5 (4.0) 3 (3.2) 1 (1.8) 11 (2.0) Brown 39 (21.9) 22 (21.8) 40 (32.3) 33 (35.1) 22 (38.6) 156 (28.1) Black 78 (43.8) 51 (50.5) 47 (37.9) 38 (40.4) 19 (33.3) 233 (42.0) Total 178 101 124 94 57 554 animals-13-00824-t003_Table 3 Table 3 Number of food sources identified during the five sampling efforts carried out in an urban area located in Divinopolis, Minas Gerais, Brazil. Sampling Efforts Community Feeders Commercial Food Outlets Total 1st 25 17 42 2nd 30 31 61 3rd 36 32 68 4th 27 27 54 5th 33 17 50 Total 151 124 275 Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000245 | An in-depth characterisation of protein and lipid fractions and changes in the physicochemical and meat-quality attributes of camel meat, beef and mutton over 9 days of refrigerated storage was investigated. The lipids of all the meat samples, especially those in camel meat, underwent significant oxidation in the first 3 days of storage. A decrease in pigment and redness (a* value) with an increase in the storage time was noticed in all the meat samples, suggesting the oxidation of the haem protein. The mutton samples displayed greater protein extractability, while the protein solubility values in all the meat samples were similar, and these varied as storage progressed. The drip loss percentage in camel meat and mutton were two times higher than in beef, and it increased during storage period. The textural properties of fresh camel meat were higher than mutton and beef, and these decreased during day 3 and 9, respectively, indicating the proteolysis and the degradation of the structural proteins, which were also evident from the SDS-PAGE pattern. camel meat beef mutton refrigerated storage protein characterisation lipid oxidation UAE University31F024 This research was funded by UAE University grant no. 31F024. pmc1. Introduction Red meat is an important source of high-quality protein that provides all the essential amino acids as well as several essential minerals, such as iron, zinc, copper and magnesium, that are required for optimal health and wellbeing . Modern nutrition guidelines recommend reducing cholesterol and saturated fatty acid intake, which has subsequently affected consumers' meat choice and preparation . Camel meat is an inherently lean meat and has low fat content compared with other commercial red meats, such as beef and mutton . Strong cultural and folklore beliefs that camel meat has medicinal benefits from its lower cholesterol concentration and relatively higher polyunsaturated fatty acids than beef have led to a higher preference for camel meat than meat from other domesticated species in several African and Middle Eastern countries . Camels possess a unique ability to thrive and tolerate harsh environmental conditions (e.g., high ambient temperature, low/irregular feed and water) and the ability to forage on plants that are not accepted by other livestock. Camels are an excellent choice for livestock production in arid and semiarid climatic conditions that are not suitable for other domesticated livestock . With global warming and increased arid/semiarid conditions in many parts around the world, camel raising represents a realistic promise to alleviate the protein shortage in these regions. Camel meat is generally considered coarse and tough because of the slaughter-age effect, where background toughness and coarser muscle fibres become prevalent . However, recent research has provided guidelines for opportunities to improve camel meat tenderness by using plant proteases . Despite its potential as an alternative meat source in arid and semiarid regions, where camels can be produced more economically than cattle can, camel meat is not widely consumed and is often misunderstood to be of lower nutritional value and quality compared with other types of red meat. This highlights the need for further research to better understand the composition and stability of camel meat during storage to improve its acceptability and potential as a source of nutritious meat. The majority of studies that have investigated camel meat have focused on its nutritional value (i.e., amino acid profile, fatty acid composition, cholesterol content and minerals content) compared with other meats to highlight its healthiness . Few studies have investigated changes in the physicochemical properties of camel meat during refrigerated storage . By reducing the rates of microbiological, chemical and biochemical changes, low-temperature storage helps to maintain the quality and freshness of meat. As a result, it is crucial to study and monitor the changes that occur in meat during low-temperature storage to ensure that its freshness and quality are maintained over time. There are no studies that have compared the quality and stability of camel meat with other red meats from the same farming background under similar storage conditions. Such comparative studies on changes in the protein and lipid characteristics of fresh camel meat compared with other common red meats such as beef (cattle meat) and mutton (sheep meat) during refrigerated storage are crucial to gaining a better understanding of camel meat stability during storage and any major issues that might affect its consumer acceptability. The objective of this study was to investigate changes in the protein and lipid compositions and the texture properties of camel meat compared with those in beef and mutton from the same farming background over 9 days of refrigerated storage at 4 degC. 2. Materials and Methods 2.1. Preparation of Meat Samples Right and left semitendinosus (ST) muscles were excised from six carcasses, each from three animal species, namely camel (males, age: 3-4 years), cattle (males; age: 3-4 years) and sheep (males, age: 2-2.5 years), and they were used in a comparative study. The animals were slaughtered in a local slaughterhouse following the United Arab Emirates Standard No. 993/2000 for animal slaughtering, which covers the requirements for halal slaughtering. The camels (Camelus dromedaries) were of the Hizami breed, the sheep were of native origin (Najdi breed) and the cattle belonged to the Chianina breed. Animals were reared in the semi-intensive management system and fed ad libitum on a Rhodes grass (Chloris gayana) hay diet. The ST muscles were manually removed from the carcasses of animals at 24-36 h postmortem, during which the carcasses were stored at 4 degC. The samples were placed in polyethylene bags stored in insulated chilling boxes during transportation to laboratory, and the samples were processed within 2 h. Each muscle was sliced into 2 cm steaks that were randomly assigned to the various biochemical and texture measurements over a 9-day storage period at 4 degC. The samples were placed in polystyrene trays that were wrapped with commercially available cling film (Falcon Food Packaging, UAE). The samples were placed in a chiller at 4 degC, and the trays were randomly rotated during the storage time and sampled at the designated storage time. 2.2. Determination of Meat Quality during Storage 2.2.1. The pH About 10 g of the meat samples was homogenised with 50 mL of chilled distilled water, and the pH values were measured with a digital pH meter (OHAUS, Starter 3100, USA) following the PN-ISO 2917:2002 method. 2.2.2. Drip Loss A 10 g sample of meat was placed in a plastic bag, which was hung from a hook and stored at 4 degC for 48 h. The drip loss (%) was determined from the weight loss of the samples upon storage at 4 degC for 48 h, as described in . After 48 h, the sample was removed from the bag, dried on absorbent paper and reweighed. The percentage of change in weight was used to calculate the drip loss by using Equation (1):(1) Drip loss (%)=(weight of sample before storage-weight of sample after storage)weight of sample before storagex100 2.2.3. Colour Colour of the ground meat samples was measured using a colorimeter (HunterLab, Model colour Flex, Reston, VIRG, USA) equipped with the light source illuminant D65 and 10deg standard observer, and a port size of 0.50 inches was used. The colour was reported in the CIE colour L*a*b* system where L*-value is lightness, a*-value is redness/greenness and b* value is yellowness/blueness. Before each measurement, the apparatus was standardised against a white plate. The measurements were carried out on days 0, 3, 6 and 9 of storage at 4 degC. 2.2.4. Textural Properties Textural properties of samples were determined using a texture analyser (CT3-4500, Brookfield Engineering Laboratories, Middleboro, USA) with a cylindrical probe that had a diameter of 50 mm. Hardness, cohesiveness, springiness, gumminess and chewiness were calculated from the force-time curves generated for each sample on day 0 and day 4. For determination of shear force values of different meat samples, cores (10 x 10 mm cross sections) were isolated from the centre of meat cubes and parallel to the muscle fibres using two scalpel blades at a fixed distance. Cores were sheared perpendicularly to the fibres in two places using a shear blade geometry attached to Brookfield texture analyser. Shear force measures the maximum force required to shear across the muscle fibre. Shear force was determined as the average of 6 peak force recordings across each muscle core. 2.3. Characterisation of Protein Fraction 2.3.1. Protein Analysis by Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE) Ground meat samples (camel meat, beef and mutton) were subjected to SDS-PAGE according to the method in Laemmli , with a slight modification, as described by Maqsood and Benjakul . The percentage of running gel and stacking gel was 10% and 4%, respectively, and 15 mg protein was loaded into each well. 2.3.2. Determination of Protein Extractability Protein extractability measurements determine the water-soluble and salt-soluble protein fractions. The measurements were carried out as described in a previous study . Meat sample (2 g) was homogenised at a speed of 11,000 rpm for 1 min in 25 mL homogenisation buffer (contained 20 mM Tris-HCl containing 50 mM KCl, pH 7.0). The homogenised mixture was centrifuged at 5000x g for 20 min at 4 degC. The protein fraction separated in the resultant supernatant was defined as "water-soluble proteins". The pellet was then homogenised in 30 mL of a high salt extraction buffer (contained 20 mM Tris-HCl containing 0.6 M KCl, pH 7.0). The homogenate was centrifuged at 5000x g for 20 min. The resultant supernatant was defined as "salt-soluble proteins". The protein concentration in the supernatants was determined by using the Biuret method, using bovine serum albumin as a standard. 2.3.3. Determination of Protein Solubility Sarcoplasmic solubility and total protein solubility were determined according to the method of Hrynets et al. , as described by Maqsood et al. . 2.4. Determination of Lipid Oxidation Products 2.4.1. Peroxide Value (PV) Meat samples were subsampled at 0, 3, 6 and 9 days of storage at 4 degC, and the PV was analysed . Knife-minced meat sample (1 g) was homogenised in 11 mL of chloroform/methanol (2:1, v/v) mixture using an Ultra-Turrax T25 homogeniser (IKA-Werke GmbH & Co., Staufen im Breisgau, Germany) at a speed of 13,500 rpm for 2 min. The PV was determined from a standard curve constructed using Cumene hydroperoxide at concentration range of 0.5-2 ppm. The PV was reported as mg of hydroperoxide/kg sample. 2.4.2. Thiobarbituric Acid Reactive Substances (TBARS) The TBARS values of meat samples were analysed using the method of Buege and Aust . 1,1,3,3-tetramethoxypropane was used to generate a malondialdehyde (MDA) standard curve at a concentration range of 0 to 10 ppm. Each TBARS value was expressed as mg of MDA equivalents/kg sample. 2.5. Determination of Meat Pigments 2.5.1. Total Haem Pigment Content Analysis Total pigment contents in the camel meat, beef and mutton samples were determined using the method of Hornsey , with some modifications. About 10 g of the ground sample was mixed with 25 mL of acidified acetone solution (contained 40 mL of acetone, 9 mL of water and 1 mL of HCl), and the mixture was homogenised at 13,500 rpm for 15 s. Another 25 mL of the acidified acetone solution was added to the mixture, and the mixture was thoroughly mixed and allowed to stand in the dark for 1 h. Next, the mixture was centrifuged at 2200x g for 10 min at 4 degC using an Allegra X-30R centrifuge (Beckman Coulter, Inc, Brea, California, USA). The supernatant was filtered with Whatman No.1 filter paper, and the absorbance was measured at 640 nm against a reagent blank. The concentration of the total pigments in the samples was calculated by multiplying the absorbance by 6800 and dividing by the sample weight, and the total pigment content is reported as mg haematin/g meat . 2.5.2. Haemoglobin Content Analysis Haemoglobin content was determined according to following Richards and Hultin and modifications suggested by Maqsood et al. . The haemoglobin concentration was calculated using a millimolar extinction coefficient of 125 for oxyhaemoglobin at pH 8 and expressed in mM. 2.5.3. Myoglobin Content Analysis Myoglobin content was determined as described by Maqsood et al. , using direct spectrophotometric measurement, and the myoglobin content was expressed as mg/g sample. 2.6. Statistical Analysis All the experimental analyses were conducted using six meat portions (n = 6) for all animals. The experiment was designed by implementing a completely randomised design, where the fixed effects were the three types of meat. Moreover, meat samples within a muscle and muscle portion within a carcass were considered as the random effects. Data were statistically analysed by a one-way analysis of variance (ANOVA) using a general linear model (GLM) procedure considering meat type as the main effect and to compare the means of the different meat-quality parameters and analysis carried out among the three types of meats during storage. The effects of species and storage time on the measured parameters and the differences between means were evaluated by Duncan's multiple range test, with a significance level of 0.05, using a SPSS package (SPSS 14.0 for Windows, SPSS Inc., Chicago, IL, USA). 3. Results 3.1. Changes in pH Mutton had a lower initial pH than that of beef and that of camel meat . There were variations in the pH of the meat samples during storage. The pH of camel meat decreased after the first 3 days of storage and thereafter increased at day 9 of storage as compared with day 0. However, a nonsignificant reduction in pH was observed for the beef sample during storage. Meanwhile, the pH of the mutton sample (pH = 7.42) significantly increased at the end of storage and was reported to be highest among the meat samples (p < 0.05). 3.2. Changes in Drip Loss The drip loss percentage in fresh camel meat and mutton were found to be significantly greater than that in beef . A gradual rise in drip loss was observed in all the meat samples when the storage time increased (p < 0.05). At the end of the 9-day storage, the rates of drip loss in fresh camel meat and mutton were found to be higher than that in beef (p < 0.05). 3.3. Changes in Protein Extractability and Solubility The fresh meat samples differed in the level of water-soluble protein (WSP) extractability and salt soluble protein (SSP) extractability (Table 1). A significantly higher WSP extractability was found in fresh beef and mutton as compared with camel meat (p <0.05). As storage progresses, increases in the WSP and SSP extraction in all the meat samples were observed. Camel meat showed significant increases in protein (WSP and SSP) extractability up to day 6. In contrast, increases in WSP extractability in beef samples were observed from day 3 to day 9, while SSP extractability increased throughout the days of storage. However, mutton showed a significant increase in both WSP and SSP at all the storage intervals as compared with day 0. At the end of the storage period, camel meat had significantly lower WSP and SSP values than beef or mutton. For the SSP extractability, initially from day 3 to day 6 of storage, mutton showed no significant difference, while towards the end of storage, significantly higher SSP extractability was noticed compared with camel meat and beef (p < 0.05). The protein solubility, both sarcoplasmic (SPS) and total protein (TPS), in camel meat and beef were similar but lower than that in mutton at day 0 (Table 1). As storage progressed, the SPS in the camel and beef meat samples significantly increased after 6 days of storage, whereas the mutton sample showed increases throughout all the days of storage. Similarly, the TPS in camel meat significantly increased on day 3; however, a significant increase in the TPS for the mutton and beef samples was observed on day 6. 3.4. Changes in Colour Parameters Camel meat had lower lightness (L*) and higher redness (a*) values than mutton and beef (Table 1). However, fresh camel meat and fresh beef samples have higher yellowness (b*) values than mutton. As storage progressed, the lightness (L*) and yellowness (b*) of the meat samples decreased (p < 0.05) from day 6 of refrigerated storage--excluding the L* value of the beef samples, which decreased throughout the storage period (Table 1). However, all the meat samples displayed a significant (p < 0.05) and gradual decrease in a* values over the course of the 9 days of refrigerated storage. Moreover, the camel redness and yellowness values decreased more significantly than those of the other species (except for an increase in a* at day 9). 3.5. Changes in Protein Pattern by SDS-PAGE The electrophoresis analyses of the protein changes in all the meat samples during the refrigerated storage of day 0 through day 9 has been shown in Figure 2. In general, during the start of the storage period, the protein pattern of all the meat samples showed clear visible bands of the major histocompatibility complex (MHC), alpha actinin, tropomyosin, actin and troponin T. At the end of storage, the band intensity significantly reduced for camel meat, and to a lesser extent for mutton meat and the smallest were for beef. The disappearance of bands corresponding to alpha actinin, tropomyosin and actin was noticed for the camel and mutton meat samples stored for 9 days. A significant degradation of the MHC was observed for all the meat samples after 9 days of storage. 3.6. Changes in Lipid Oxidation Products The peroxidase values in fresh camel meat and fresh beef were significantly (p < 0.05) higher than those in fresh mutton . The storage of the meat samples for 3 days increased the PV of both the camel meat and beef samples, where the camel meat had the highest PV. However, the PV in the meat samples started to decrease as the storage period increased from day 3 to day 9, but the camel meat had the highest PV as compared with beef and mutton at the end of the 9-day storage period (p < 0.05). The fresh camel meat displayed a significantly higher TBARS value than fresh beef or fresh mutton did (p < 0.05). During storage, a sharp rise in the TBARS value in camel meat was observed in the first 3 days of storage (p < 0.05), thus indicating its high susceptibility to lipid oxidation. However, beef showed a gradual increase in the TBARS value from day 3 to day 9 of storage (p > 0.05). As storage progressed, there was variation in the rate of change in the TBARS in camel meat, while a slight increase in the TBARS value was noticed in beef (p > 0.05). Unlike other meat samples, there was no change in the TBARS value of mutton during storage (p > 0.05). 3.7. Changes in Total Pigment, Haemoglobin and Myoglobin Fresh camel meat had a higher total haem content (67.32 mg haematin/g of sample) than beef (60.38 mg haematin/g of sample) or mutton (40.25 mg haematin/g of sample) . The total haem content in camel meat and that in beef significantly (p < 0.05) decreased during the first 3 days of storage, and thereafter, the values were similar as storage progressed (p > 0.05). The fresh camel meat and beef samples had similar haemoglobin contents (p > 0.05), and the values were significantly higher (p < 0.05) than that of fresh mutton . However, the fresh beef and fresh mutton had lower myoglobin contents than camel meat (p < 0.05). The haemoglobin contents in the meat samples started to decrease from day 3 of storage, with a sharp decrease observed in beef and mutton (p < 0.05). However, a gradual decrease in the myoglobin contents as the storage period increased until day 9 was noticed in all the meat samples. The total haem value plays a significant role in the colour of fresh meat . 3.8. Changes in Textural Properties Table 2 compares the textural properties of the meat samples at day 0 and day 9 of refrigerated storage. On day 0 of storage, camel meat had significant values (p < 0.05) and the highest values for hardness, gumminess, chewiness and shear force, followed by beef, while mutton had the lowest values. All the measured textural parameters decreased from day 0 to day 9 of storage. A comparison of the meat samples on day 9 of storage showed that mutton had significant lower values (p < 0.05) for hardness and that camel meat had the lowest values for gumminess, respectively. Moreover, camel meat had the highest chewiness and shear force values compared with beef and mutton. 4. Discussion The pH of meat is highly important because it has a major influence on other physicochemical and quality properties, such as water-holding capacity, tenderness and juiciness. The pH values of the meat samples in this study showed higher values (6.34-6.54) compared with other studies on beef (pH = 5.50) and sheep (pH = 5.60) meat at day 0. The variation in the pH values of camel meat during storage could be attributed to the high gluconeogenesis capacity of camels due to the presence of a camel hump, and the number of enzymes in its glycolytic pathway causes slower glycogen degradation and thus pH decline . Similar to the pH of beef in this study, a nonsignificant change in pH for coarsely and finely marbled grade 1+ Hanwoo beef loins was observed during 14 days of storage at 2 degC . Changes in pH are caused by postmortem metabolism . Moreover, the difference in the rate of change in small letters pH of small letters meat samples could be attributed to the glycogen storage in the muscle at the time of slaughter. The increase in drip loss during storage might be due to a greater loss of small letters water-holding property of the muscle protein due to degradation, and most of the proteins found in drip are water-soluble and sarcoplasmic proteins . Similarly, the drip loss in packed camel meat significantly increased as storage duration increased . The higher drip loss in fresh camel meat and mutton could be related to the lower intramuscular fat found in camel meat and mutton as compared with beef . Intramuscular fat could act as a barrier to prevent fluid from passing, so the higher the fat, the lower the fluid loss . The drip loss of meat may contribute to the lower consumer acceptability of meat, due to the fewer taste constituents remaining, and may contribute to the shrinkage of meat . Our findings on WSP and SSP extractability are similar to those reported in porcine longissimus muscle during storage . The high redness and yellowness in fresh camel meat may be due to the highest amount of haem pigment and myoglobin contents found in fresh camel meat as compared with the other two meat types . Similarly, Kadim et al. found that meat from the camel longissimus muscle had a greater b* value than that of beef. The redness (a*) value of the beef after storage would meet the desired consumer thresholds of 14.5 for beef . However, the a* values of mutton before and after storage were less than the desired threshold of 14.4 for fresh lamb . The decrease in the a* value during storage may be due to the oxidation of oxymyoglobin to form metmyoglobin . During the postmortem storage of meat, myoglobin in the ferrous state (+2) is oxidised to form ferric (+3) metmyoglobin, resulting in a brownish-red meat . In addition, the observed colour change was in agreement with the decrease in the total haem pigment and myoglobin content during the storage of the meat samples. As shown in the protein profiles of the meat samples, the higher protein degradation could have occurred because of the protein oxidation during storage, which could have led to the fragmentation and lysis of structural proteins . Generally, a mild degradation of the beef protein was revealed compared with that of camel and mutton meat. The degradation of troponin T occurred during the postmortem storage of beef and camel meat for a period of 7 days . Our findings agree with this study in that we have also observed a marked degradation of bands corresponding to troponin T in all the three meat types during 9 days of storage. The degradation in troponin T was related to protein degradation and increased tenderness during storage . Additionally, proteolysis by endogenous proteases during extended storage is responsible for protein degradation and the tenderisation of meat . Lipid oxidation is an important factor influencing the quality of meat by affecting its flavour, colour, texture and nutritive value. Similar to this study, a decrease in the PV during storage was reported in the PV of chicken leg and breast meat during frozen storage. The rise in the PV in camel meat and beef may be due to the faster rate of peroxide formation during the first 3 days of refrigerated storage, followed by their degradation into secondary oxidation products during the extended storage period of 9 days. Also, the high PV found in the camel meat could be due to the higher haemoglobin and myoglobin contents of camel meat compared with those of beef and mutton given that these iron-containing pigments have been found to be effective catalysts for lipid oxidation . As compared with day 0, the increase in TBARS in camel meat and beef during storage may be due to the degradation of hydroperoxides into secondary oxidation products, especially aldehydes, in the later stages of lipid oxidation . Moreover, camel meat is known to contain higher numbers of the myoglobin and other haem compounds that function as pro-oxidants to promote lipid oxidation . Furthermore, the denaturation of haem protein leads to the release of iron, which acts as a strong pro-oxidant and accelerates lipid oxidation . Therefore, the high iron contents in camel meat after 9 days of storage (Supplementary Table S1) could be responsible for its high lipid oxidation products compared with beef and mutton. Similarly, a direct proportionality between haem pigment degradation and an increase in lipid oxidation during the storage of camel meat has been reported . The variation in the total haem contents during storage could be due to the denaturation and oxidation of the pigment during storage, leading to the lower pigment content remaining or bound in the muscle . Similar findings have been reported in raw minced sheep and sardine and mackerel fish muscle during refrigerated storage for 14 and 15 days, respectively. The oxidation of haem leads to the deep-yellow or brown discoloration of meat. The decrease in the total pigment corroborates well with the decrease in redness (a*) during storage from day 0 to day 9. The haemoglobin and myoglobin contents found in camel meat are comparable with those reported in a previous study on camel meat, but the values were higher than those of beef and mutton found in the present study. The loss of myoglobin in the meat samples during storage could be due to its oxidation or degradation and loss of sarcoplasmic fluid (i.e., purge) . Furthermore, haemoglobin and myoglobin are known to be potent catalysts of lipid oxidation in muscle foods . Therefore, the high haemoglobin and myoglobin contents in camel meat may contribute to the rate of lipid oxidation in the camel meat sample during storage. A decrease in the textural properties of all the meat samples as storage progressed may be attributed to the structural breakdown of myofibrils and the degradation of meat proteins during the course of refrigerated storage, as shown in the SDS-PAGE profile. Furthermore, the proteolytic action promoted by muscle endopeptidases, resulting in tenderising the meats during 9 days of refrigerated storage, could not be ruled out. Similar to this study, camel meat was perceived to be tough and fibrous in . Meat tenderness is greatly influenced by species, which could be due to differences in the coarseness of their musculature . Furthermore, the shear force values in animal muscles have been reported to increase with the increasing age of the animal , and this was attributed to the changes in the connective tissues of the animals as the animals mature . Therefore, the high shear force values in camel meat and beef in this study may be due to the old age of the animals as compared with the younger age of the animals from which the mutton samples were taken. Tenderness is an important quality attribute of meat, and therefore, suitable cooking methods should be selected for the cooking of the meats, particularly for stored camel meat, to improve the tenderness of the meat. 5. Conclusions This study provided a characterisation of the protein and lipid fractions of three commercially important red meat (camel meat, beef and mutton), as well as changes occurring in their physicochemical and meat-quality attributes during 9 days of refrigerated storage. Camel meat was found to be highly susceptible to lipid oxidation during storage, and this may have been due to its high haem (haemoglobin and myoglobin) content and high percentage of polyunsaturated fatty acids. Protein extractability was found to be higher in mutton species, while protein solubility did not show any difference among the three animal species investigated. Increased drip loss was reported in the camel and mutton samples during the storage period. Camel meat was tougher, with higher hardness values, followed by the beef and mutton samples' values, which decreased during 3 days and 9 days of storage, indicating the degradation of structural proteins. In conclusion, the study provided valuable information on the properties of different red meats during storage and variations in their protein and lipid fractions and other quality attributes during storage. Acknowledgments The authors are thankful for the research grant (No. 31F024) from United Arab Emirates University for providing the funding to conduct this research. Supplementary Materials The following supporting information can be downloaded at Table S1: Mineral composition of camel meat, beef and sheep meat at day 9 of storage. Click here for additional data file. Author Contributions K.M. (Kusaimah Manheem): methodology; investigation; formal analysis; validation; writing--original draft. O.A.: writing--original draft; writing--review and editing. U.R.: writing--review and editing; revision. K.M. (Khaja.Mohteshamuddin).: writing--review and editing; revision. H.M.H.: formal analysis; methodology. N.P.N.: writing--review and editing; validation. S.M.: conceptualisation; funding acquisition; project administration; supervision; writing--review and editing. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Changes in pH (a) and drip loss (%) (b) in camel meat, beef and mutton over 9 days of refrigerated storage. Data are represented as mean +- SEM (n = 6). Figure 2 Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) pattern of proteins extracted from camel meat, beef and mutton on day 0 and day 9 of refrigerated storage. Notes: CM 0 and CM 9; BF 0 and BF 9; and MT 0 and MT 9 denotes camel meat, beef and mutton on day 0 and on day 9 of storage, respectively. Figure 3 Changes in lipid oxidation products (peroxide value (a) and TBARS (b)) in camel meat, beef and mutton during 9 days of refrigerated storage. Data are represented as mean +- SEM (n = 6). Figure 4 Changes in total pigment (a), haemoglobin content (b) and myoglobin content (c) in camel meat, beef and mutton during 9 days of refrigerated storage. Data are represented as mean +- SEM (n = 6). Figure 5 A picture showing meat chunks from camel, beef and mutton and their extracted haem pigments. animals-13-00904-t001_Table 1 Table 1 Changes in protein extractability and solubility, and colour properties of camel meat (CM), beef (BF) and mutton (MT) over 9 days of refrigerated storage. Parameters Sample Storage Time (Days) 0 3 6 9 Protein extractability (Water-soluble protein) (mg of protein/g of sample) CM 3.13 +- 0.01 bB 3.51 +- 0.01 bA 4.00 +- 0.00 bA 4.04 +- 0.05 bA BF 3.44 +- 0.01 aC 3.48 +- 0.02 bC 4.58 +- 0.01 aB 4.86 +- 0.01 aA MT 3.41 +- 0.02 aC 4.35 +- 0.02 aB 4.58 +- 0.01 aAB 4.76 +- 0.01 aA Protein extractability (Salt-soluble protein) (mg of protein/g of sample) CM 1.35 +- 0.02 bC 1.67 +- 0.02 bB 2.02 +- 0.01 aA 2.06 +- 0.0 cA BF 1.40 +- 0.02 bC 1.87 +- 0.01 bB 1.98 +- 0.01 aB 2.59 +- 0.02 bA MT 1.96 +- 0.01 aC 2.18 +- 0.02 aB 2.18 +- 0.01 aB 3.01 +- 0.02 aA Sarcoplasmic protein solubility (mg of protein/g of sample) CM 3.83 +- 0.02 bC 3.97 +- 0.06 bC 4.56 +- 0.01 cB 5.06 +- 0.02 cA BF 3.78 +- 0.01 bB 3.95 +- 0.02 bB 5.19 +- 0.01 bA 5.36 +- 0.02 bA MT 4.96 +- 0.02 aD 5.21 +- 0.02 aC 5.42 +- 0.01 aB 5.81 +- 0.16 aA Total protein solubility (mg of protein/g of sample) CM 9.86 +- 0.11 bB 11.88 +- 0.05 aA 12.03 +- 0.09 bA 12.62 +- 0.02 bA BF 10.17 +- 0.05 bB 11.59 +- 0.07 aB 13.12 +- 0.02 aA 13.61 +- 0.03 aA MT 11.12 +- 0.03 aC 11.69 +- 0.07 aBC 12.52 +- 0.01 abAB 12.79 +- 0.02 abA L* CM 41.69 +- 0.24 cA 40.91 +- 0.38 cA 35.61 +- 0.66 bB 34.55 +- 0.73 bB BF 45.58 +- 0.26 bA 43.88 +- 0.08 bB 42.16 +- 0.20 aC 39.67 +- 0.13 aD MT 46.84 +- 0.05 aA 46.27 +- 0.03 aA 43.38 +- 0.22 aB 41.31 +- 0.12 aC a* CM 21.67 +- 0.18 aA 18.13 +- 0.39 aB 12.43 +- 0.22 aC 17.74 +- 0.20 aB BF 18.74 +- 0.32 bA 15.98 +- 0.13 bB 14.85 +- 1.83 bD 14.73 +- 0.15 bC MT 13.84 +- 0.28 cA 11.43 +- 0.09 cC 10.18 +- 0.12 bD 12.59 +- 0.12 cB b* CM 17.10 +- 0.22 aA 16.34 +- 0.13 aA 11.05 +- 0.26 cB 9.945 +- 0.14 cC BF 16.97 +- 0.24 aA 16.40 +- 0.07 aA 14.74 +- 0.16 aB 14.56 +- 0.13 aB MT 15.82 +- 0.19 bA 15.27 +- 0.03 bA 13.08 +- 0.07 bB 12.32 +- 0.15 bC Values are mean +- SEM (n = 9). Different small letters within the same column under the same tested parameter indicate significant differences (p < 0.05). Different capital letters within the same row under the same parameter indicate significant differences (p < 0.05). animals-13-00904-t002_Table 2 Table 2 Changes in the textural properties of camel meat (CM), beef (BF) and mutton (MT) on day 0 and day 9 of refrigerated storage. Storage Time Samples Hardness (N) Cohesiveness Springiness (mm) Gumminess (g) Chewiness (mJ) Shear Force (N) Day 0 CM 37.26 +- 0.08 a 0.85 +- 0.08 a 6.99 +- 0.08 a 1906.3 +- 5.06 a 98.12 +- 0.08 a 58.05 +- 3.04 a BF 30.49 +- 0.06 b 0.89 +- 0.06 a 6.97 +- 0.12 a 1701.8 +- 5.92 b 72.97 +- 0.05 b 49.22 +- 1.66 b MT 27.06 +- 0.07 d 0.83 +- 0.04 ab 6.91 +- 0.10 a 1182.4 +- 3.72 c 51.63 +- 0.07 d 45.40 +- 1.17 c Day 9 CM 28.59 +- 0.05 c 0.72 +- 0.04 c 5.88 +- 0.09 b 945.1 +- 3.23 e 52.69 +- 0.06 d 51.48 +- 1.96 b BF 28.43 +- 0.04 c 0.76 +- 0.03 bc 5.84 +- 0.07 b 992.7 +- 3.46 d 47.48 +- 0.06 c 41.58 +- 1.96 cd MT 26.25 +- 0.03 e 0.72 +- 0.02 c 5.78 +- 0.03 b 1178.3 +- 2.45 f 46.54 +- 0.04 c 38.73 +- 1.96 d Values are mean +- SEM (n = 6). Different small letters in the same column for each parameter on day 0 and day 9 of storage indicate significant differences (p < 0.05). 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PMC10000246 | Porcine reproductive and respiratory syndrome (PRRS) is an acute, febrile, and highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Glycoprotein 5 (GP5) is a glycosylated envelope protein encoded by the PRRSV ORF5, which has good immunogenicity and can induce the body to produce neutralizing antibodies. Therefore, study of GP5 protein is of great significance in the diagnosis, prevention, and control of PRRSV and the development of new vaccines. We reviewed GP5 protein genetic variation, immune function, interaction with viral protein and host proteins, induction of cell apoptosis, and stimulation of neutralizing antibodies. GP5 protein's influence on virus replication and virulence, as well as its use as a target for viral detection and immunization are reviewed. porcine reproductive and respiratory syndrome virus GP5 protein host proteins vaccines National Natural Science Foundation of China31902279 31902284 Guangdong Science and Technology Program Project2021A1515012388 2017A020208079 Guangdong Basic and Applied Basic Research Foundation2021A1515110322 This research was funded by the National Natural Science Foundation of China (31902279, 31902284), Guangdong Science and Technology Program Project (2021A1515012388, 2017A020208079), and the Guangdong Basic and Applied Basic Research Foundation (2021A1515110322). pmc1. Introduction Porcine reproductive and respiratory syndrome (PRRS) is a severe infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). The disease is characterized by adverse reproductive outcomes such as miscarriage, premature delivery, stillbirth, and fetal mummification. Non-reproductive effects are exhibited as respiratory diseases, immunosuppression, secondary diseases, and increased piglet mortality. These effects combine to cause massive economic losses to the swine industry worldwide. PRRS outbreaks initially occurred in the United States in 1987, and then spread to Europe and Asia ; it was initially called the "mystery pig disease" by the American Animal Health Society in 1990 . In 1991, PRRSV was isolated from diseased animals in the Netherlands and named Lelystad virus (LV) . PRRSV was isolated in the United States in 1992 and named SIRS virus (also known as VR-2332) . According to its genetic and antigenic characteristics, PRRSV can be divided into two genotypes: the European type (PRRSV-1) represented by the LV strain and the American type (PRRSV-2) represented by the VR-2332 strain . The two types share approximately 60% of their nucleotide identity . The first PRRSV strain of China, isolated and identified from aborted fetuses in 1996, was classified as PRRSV-2 . In 2006, an outbreak of highly pathogenic PRRSV (HP-PRRSV) characterized by high mortality, fever, and abortion rates devastated the Chinese swine industry . PRRSV is an RNA virus with an envelope and single positive strand , belonging to the order Nidovirales and the family Arteriviridae. It also includes lactate dehydrogenase-elevating virus of mice, equine arteritis virus, and simian hemorrhagic fever virus . The total length of the genome is approximately 15 kb, which forms a cap structure at the 5' end during mRNA processing, and has a poly-A tail structure at the 3' end . The PRRSV genome contains 12 open reading frames (ORFs): ORF1a, ORF1a', TF, ORF1b, ORF2a, ORF2b, ORF3, ORF4, ORF5a, and ORF5-ORF7 . Among them, ORF1a and ORF1b encode polyproteins pp1a and pp1b, which can be processed into 17 nonstructural proteins (NSPs) (NSP1a, NSP1b, NSP2, NSP2N, NSP2TF, NSP3-14) that play a major role in virus replication . ORF5 and ORF6 encode the major GP5 and M envelope proteins, respectively, which interact with each other to form heterodimers on the surface of virus particles. GP5 is one of the most variable regions of structural proteins in the PRRSV genome and is, therefore, often used for phylogenetic analyses. ORF2, ORF3, and ORF4 encode the minor GP2a, GP3, and GP4 proteins that form noncovalent heterodimers. Two small non-glycosylated proteins E and GP5a are encoded by ORF2b and ORF5a, respectively. ORF7 encodes the highly conserved nucleocapsid protein (N protein) . GP5 protein is highly variable in PRRSV as it plays an important role in virus infection, as well as simultaneously inducing protective antibodies in the host. Therefore, it is a good target antigen for developing new vaccines . GP5 protein contains important immune domains related to virus neutralization as well as some peptides or protein motifs, including signal peptides, transmembrane regions, antigenic determinants, and glycosylation sites . As GP5 protein is greatly involved in the invasion, adsorption, and proliferation of PRRSV, it is of great interest to the pathogenicity, diagnosis, prevention, and control of PRRSV . 2. Overview of GP5 Protein GP5 protein is a glycosylated envelope protein encoded by the PRRSV ORF5 gene. Its molecular weight is approximately 25 kDa, and it is composed of approximately 200 amino acids . It is divided into four parts: the N-terminal, which is a signal peptide composed of 32 amino acids; the external functional region, which is composed of 35 amino acids containing varying numbers of glycosylated sites; the hydrophobic region, which is composed of 60 amino acids and three transmembrane domains; and the hydrophilic region, which is at the C-terminal end . The extracellular domain of GP5 protein in the American strain contains four N-glycosylation sites, of which N44 and N51 are of the conservative type, which primarily affect the virus infectivity . Glycosylation of GP5 protein may cause the immune escape of the virus, thus reducing the protection of the host's immune response . The multiple transmembrane hydrophobic regions contained in GP5 protein can make the translated GP5 protein stay in the endoplasmic reticulum, thus inhibiting its expression . GP5 and M proteins of PRRSV are mainly incorporated into virus particles in the form of disulfide-linked heterodimers or polymers, which are essential for virion formation . 3. Genetic Variation Analysis of GP5 Protein PRRSV GP5 protein has high genetic variation in the PRRSV genome . GP5 protein of the European strain is composed of 201 amino acids, while that of the American strain is composed of 200 amino acids . The amino acid homology deduced from the PRRSV isotype strain of GP5 is between 88% and 99%, while that deduced from GP5 between the European and American strains is between 52% and 55%. The substitution of deduced amino acids of GP5 among strains of the same type mainly occurs in the hypervariable region (26 aa-39 aa) near the outer region of the signal peptide sequence , whereas, the amino acid variation of GP5 protein of different strains is mainly concentrated in the signal peptide region, neutralizing epitope region, and non-neutralizing epitope region . Zhang et al. amplified the ORF5 of 16 PRRSV strains in different areas of Shandong Province using reverse transcription-polymerase chain reaction (RT-PCR) and performed a sequence analysis. The results showed that there were site mutations in the amino acids of GP5 protein in all 16 strains, from which 12 strains had mutations at the 29th site of the non-neutralizing epitope and the 34th site of quasi-species evolution, from V to A and N to S, respectively. One strain mutated from A to V at the 185th site of the non-neutralizing epitope. Similarly, Li et al. used RT-PCR to analyze the genetic variation of the isolated PRRSV ORF5 gene. The results showed that the 13th and 151st amino acids and neutralizing epitope (36 aa-52 aa) of ORF5 were mutated, which could lead to changes in virulence and immune evasion. In another study, Lu et al. isolated nine Henan strains and reported that the 39th amino acid of all isolates except HeN-3 had changed from F/L to I . In 2011 and 2012, the mutation of the neutralizing epitope Q40, L41, and the new mutation of the decoy epitope L28 in GP5 protein were found in PRRSV strains in Heilongjiang province . In 2014, the amino acid sites of GP5 in South China were analyzed and found to have extensive variations in the signal peptide region, induced epitope, neutralizing epitope, and hypervariable region of the new branch subgroup . Besides the mutation of amino acid sites, many studies have shown that the 33rd amino acid of PRRSV GP5 protein is deleted. Jiang et al. reported that the GD-HY strain had an amino acid deletion at the 33rd site. Zhou et al. showed that the ORF5 gene of SCcd17 encodes a 199 aa protein and has a novel 1 aa deletion in hypervariable region 1 (HVR1) at the 33rd site. Zhang reported that the 32nd and 33rd amino acids of the strains were deleted, and the glycosylation sites of GP5 were increased and complexed. In addition, H38-K38 mutation occurred in the epidemic strains. Fan et al. reported that SD7, SD8, and SD9 strains were absent in the 34th amino acid. Via phylogenetic analysis based on GP5 amino acids, Sun et al. revealed that the novel NADC30-like PRRSV with a unique single amino acid deletion at the 34th site has become widespread and evolved into a new subgroup. The gene sequences of representative PRRSV strains were analyzed. A total of 32 target gene sequences of PRRSV GP5 were obtained. To construct the phylogenetic tree, nucleotide sequences of the target gene were aligned using the ClustalX alignment tool and MEGA software (version 7.0.26, Mega Limited, Auckland, New Zealand). Phylogenetic trees were constructed using the neighbor-joining method with 1000 bootstrap replicates in MEGA7.0 . JN-1 and TAXT are similar to the reference strain JXA1, but far from the strain VR2332, and DLS-1 is in a single branch. Furthermore, Zhao et al. reported that a new insertion site (Lys57) appeared at the 57th site of GP5 protein, which was in the hypervariable region (32 aa-35 aa). PRRSV GP5 protein can easily mutate, which leads to the diversity of strains, increases the difficulty of vaccine development, and makes the disease difficult to control. In conclusion, GP5 protein is highly variable in PRRSV and plays an important role in monitoring variations in PRRSV. 4. Immune Function of GP5 Protein GP5 protein is the main protective antigen targeted by neutralizing antibody induced by PRRSV vaccination or prior infection. The protein has six antigenic determinants. It contains two B cell antigen epitopes: a non-neutralizing epitope A and a neutralizing epitope B. Epitope B induces the body to produce specific neutralizing antibodies against the viral infection. In contrast, epitope A inhibits the recognition of epitope B in the body, thus delaying the production of neutralizing antibodies . Studies show that inserting a Pan-DR T-helper cell epitope (PADRE) between the neutralizing and bait epitopes can reduce or eliminate the bait effect of the non-neutralizing epitope . The reaction between the monoclonal antibody and the expressed product of the deletion mutant shows that GP5 protein has at least two antigenic regions: one extracellular region (27 aa-41 aa) and one at the C-terminal (180 aa-197 aa). The 50 amino acids in the C-terminal of GP5 protein play an important role in maintaining its antigenicity. If these amino acids were absent, GP5 protein would lose its reactivity with the antibody . Akter et al. . showed that the loss of glycan residues in N-linked glycosylation sites (N34, N44, and N51) enhances the immunogenicity of the nearby neutralizing epitope. Leng et al. found that the B antigen region (AR) of HP-PRRSV GP5 did not neutralize AR. The results of indirect enzyme-linked immunosorbent assay (ELISA) and a virus neutralization test showed that there was no correlation between the levels of anti-B AR polypeptide antibody and neutralizing antibodies in the serum of pigs. The specific serum antibody of AR peptide has no neutralizing activity, and glutathione S-transferase-B (GST-B) fusion protein cannot inhibit the neutralizing ability of the antibodies. Three putative N-linked glycosylation sites (N34, N44, and N51) are located in the extracellular domain of GP5, which also include major neutralizing epitopes. Yin et al. indicated that its peptide segments 30-36, 50-55, 140-142, 146-151, and 196-198 may be its dominant B cell epitope regions. Furthermore, T-cell epitopes of PRRSV in GP5 protein have been found (119 aa-127 aa and 151 aa-159 aa) . Zhang et al. used an infectious clone of PRRSV as a vector and replaced Asn with Ala at the 34th or 51st site of GP5 protein. After transfecting the cells, they obtained PRRSV mutants, vVR-N34A and vVR-N51A, which may have been related to the immunogenicity of neutralizing epitope B. The neutralization test results preliminarily suggested that the glycosylation of PRRSV GP5 protein played a role in the host immune function and affected the relationship between the virus and specific neutralizing antibodies. Wang et al. analyzed the carboxyl terminal of PRRSV GP5 protein and predicted and screened the region with a high antigenicity index to construct recombinant phage M13-GP5 168 aa-198 aa. Western blot results showed that the recombinant phage had good reactivity, and the neutralization test confirmed that it could induce piglets to produce high levels of neutralizing antibodies. The latest research shows that a new immune escape mechanism of PRRSV infection has been discovered. Li et al. demonstrated N-terminal acetylation by N-acetyltransferase Nat9 as a novel host defense mechanism that leads to K27-linked-ubiquitination-dependent proteolysis of GP5, which contributes to inhibiting PRRSV infection and proliferation in 3D4/21 cells. 5. Apoptosis Induction by GP5 Protein GP5 protein not only plays a role in PRRSV infection, cell binding, and virus adsorption, but also in cell apoptosis. In 1996, studies revealed that PRRSV GP5 protein caused strong cytotoxicity, and the apoptosis induced by GP5 was independent of anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) . This apoptosis activity could not be prevented by using cell lines that permanently express Bcl-2 protein, which indicates that GP5 either induces apoptosis downstream of Bcl-2 or employs another unknown apoptosis pathway . In vitro, the constructed cells expressing GP5 exhibit typical apoptosis phenomena, such as gradient fragmentation of genomic DNA, reduction of cell number, and formation of apoptotic bodies . Shen found that mutations at different glycosylation sites of PRRSV GP5 protein had different effects on apoptosis induction. Among them, the mutation of N34 and N35 glycosylation sites led to a significant increase in cell apoptosis, whereas the mutation of other sites did not cause any significant effects. Fernandez et al. used recombinant vaccinia virus to express PRRSV GP5 protein in mammalian cells. They found that the first 119 amino acids constituted a region that induced apoptosis due to the resulting strong cytotoxicity. The C-terminal region did not induce apoptosis. Hela cells stably expressing GP5 did not show evidence of apoptotic cell death and they speculated that the difference might be due to a histidine tag and an antigenic tag placed in the N-terminal of GP5 fusion constructs. GP5 protein of the PRRSV SD16 strain inhibits virus replication and leads to G2/M cell cycle arrest, but it does not induce Marc-145 cell apoptosis . Similarly, Ma et al. demonstrated that none of the PRRSV structural proteins, including GP5, had the potential to cause apoptosis in Marc-145 cells. Rather, NSP2 and NSP4 played causative roles in PRRSV-induced apoptosis in Marc-145 cells. Some studies have also found that the expression of GP5, GP584-96, and GP597-119 changes the ratio of Bax/Bcl-2 to different degrees but does not cause the apoptosis of Marc-145 cells . Therefore, the definitive role of GP5 in apoptosis induced by PRRSV is still unknown. 6. Effects of GP5 Protein on Virus Replication GP5 protein plays an important role in PRRSV replication. Song et al. found that a stable expression of GP5 in Marc-145 cells promoted virus replication at the early stage of PRRSV infection by downregulating interferon (IFN) expression; in contrast, interfering GP5 expression with specific small interfering RNA (siRNA) inhibited PRRSV replication. Wang et al. found that the expression of GP5 D84-119 inhibited PRRSV replication by upregulating IFN expression, especially IFN-b, and that the second extracellular region of GP5 played a regulatory role in PRRSV replication. Song et al. successfully constructed three short hairpin RNA (shRNA) expression plasmids targeting the PRRSV GP5, which confirmed that the shRNA could effectively inhibit PRRSV replication in Marc-145 cells. They also screened two deoxyribozymes targeting the PRRSV GP5, which confirmed that the designed deoxyribozymes could effectively inhibit PRRSV replication in Marc-145 cells. Furthermore, a study by Wei et al. evidenced that all N-linked glycans in GP5 are not required for virus viability in vitro but are essential for virus replication in vivo. In a different study, Niu et al. studied the effect of PRRSV GP5 protein on the phosphorylation of interferon regulatory factor-3 (IRF-3) in the IFN signaling pathway. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis results showed that GP5 protein could inhibit the phosphorylation of IRF-3. 7. Interaction between GP5 Protein and Viral Protein GP5 and M proteins are the main envelope proteins of PRRSV, which make up more than half of the virus proteins. They can form a heterodimer GP5/M linked by disulfide bonds in virus-infected cells, which is essential for protein transport, assembly, and outflow of progeny virions. Its immunogenicity is strong and conservative, and it allows virus budding to occur on the membrane of the exocytosis pathway . The GP5/M protein complex of PRRSV adheres to saliva expressed on cells in order to infect them . When PRRSV was used to infect peptidylgycine a-amidating monooxygenase treated with heparinase, the dimer of M and GP5 proteins was conveniently bound to heparin-like receptors on peptidylgycine a-amidating monooxygenase cells . Zhang et al. found that GP5 and M proteins of PRRSV-1 and PRRSV-2 strains were palmitoylated at cysteine, whether they were expressed alone or in PRRSV-infected cells. Viruses lacking one or two acylation sites in M or GP5 could be saved, but their titers were significantly reduced; in addition, the GP5 and M lacking acylation sites had formed a dimer. Ma et al. used enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) as tracers and found that when ORF5-EGFP and ORF6-RFP were co-expressed, GP5 protein could be transported from the endoplasmic reticulum to the high matrix, suggesting that the formation of the GP5/M heterodimer may be related to the post-translational modification, transport, and localization of GP5 protein. 8. Interaction between GP5 Protein and Host Proteins Xue et al. found that the outer domain (GP5-ecto-1) of the first GP5 directly interacts with non-muscle myosin heavy chain 9 (MYH9) C-terminal domain protein (PRA), and this interaction triggers PRA and endogenous MYH9 to form a silk assembly. MYH9 plays a pivotal role in PRRSV infection by physically interacting with PRRSV GP5 protein through its C-terminal domain, which makes the host cells susceptible to infection . Du et al. screened two types of host proteins using immunoprecipitation, namely, the mitochondrial inner membrane protein and calpain protein, both of which interact with GP5. These proteins can co-locate with GP5 in cells and are related to cell protein glycosylation, cell growth, proliferation, movement, function, and maintenance, as well as the development and function of the nervous system. GP5 contains a T4L (T4 lysozyme)-like domain that locally digests the peptide glycan layer during infection. T4 Spackle protein (encoded by gene 61.3) plays a role in inhibiting GP5 lysozyme activity . Hicks et al. found that GP5 protein interacts with Snapin of the Marc-145 cell line to take advantage of its role in intracellular transport and membrane fusion. Recent studies revealed that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) interacts with GP5 by binding to 13 of its amino acid sequences (93 aa-105 aa), while GP5 interacts with GAPDH at the K277 amino acid. This indicates that during PRRSV infection, GP5 interacts with GAPDH in the cytoplasm to restrict it from entering the nucleus, and PRRSV promotes virus replication by utilizing glycolysis activity of GAPDH . Zhang et al. In cloned porcine ATP synthase subunit alpha (ATP5A) into the vector pFLAG-CMV-2 and transfected human embryonic kidney (HEK) 293 cells with pCI-GP5 along with pFLAG-CMV-2 or pFLAG-pig-ATP5A. Co-immunoprecipitation was performed using anti-FLAG affinity beads, and the immune complexes resolved by SDS-PAGE were probed with either anti-FLAG or anti-GP5 antibodies. The results showed that ATP5A was readily detected only in the presence of GP5 and not in the presence of empty vector. Thus, it is confirmed that GP5 can interact with ATP5A. Understanding the molecular mechanism of the interaction between PRRSV GP5 and host proteins can lay the foundation for finding new antiviral targets and exploring the mechanism of viral replication. 9. Influence of GP5 on Virulence Wesley et al. compared the amino acid sequences of VR-2332 with its attenuated vaccine. Their study revealed that the mutation of Arg to Asn at the 13th site and Arg to Gly at the 151st site of the American strain was related to the virulence weakening of the vaccine strain. Hence, the 13th amino acid (R13) and the 151st amino acid (R151) in GP5 protein were the sites related to PRRSV virulence. Studies have also shown that the glycosylation sites of certain Chinese strains have changed remarkably since 2006, and the absence of the 33rd glycosylation site and appearance of the 34th and 35th glycosylation sites may be related to the enhancement of PRRSV virulence . Wang et al. found that the 55th site mutations occurred in GP5 of the Guizhou epidemic strain through cloning and sequencing, and the site mutations at the 25th, 26th, 358th, 409th, and 554th nucleotides could lead to the loss or appearance of some enzyme cut-sites. The 55th site mutations in GP5 may play a vital role in the enhancement of PRRSV virulence. Most strains have high arginine-glutamine (RQ) motifs near their carboxyl terminal. Further, the highly conserved RQ motifs overlap with the hypervariable GP5 glycosylation sites, which may influence PRRSV virulence . 10. Applications of GP5 Protein in Vaccines At present, the PRRSV vaccines used in China are mainly inactivated vaccines, such as CH-1a, or attenuated vaccines, such as CH-1R. Some vaccines on the market are listed in Table 1. The inactivated vaccines have poor immune efficacy, short immune protection time, and limited protection against heterologous strains; whereas the attenuated vaccines pose a risk of virulence reversal and have short immune protection time that cannot prevent a strong viral infection. Therefore, the development of efficient, safe, and affordable vaccines has become a trending research topic in recent years. GP5 protein has good immunological properties and induces neutralizing antibodies, making it the preferred protein for developing new vaccines. These vaccines primarily include nucleic acid, subunit, and live vector vaccines. Nucleic acid vaccines, also known as DNA vaccines, induce cellular and humoral immunity simultaneously and have cross-protection to different serotypes of strains. Baroed et al. cloned all the ORFs of PRRSV Danish isolates (DK-111/92) in a DNA vaccine vector, and inoculated pigs. The results showed that the pigs immunized with vaccines prepared using ORF1 and ORF4 quickly developed antibody immune responses against NSP2 and GP4; moreover, neutralizing antibody was detected in all pigs, but those inoculated with ORF5 showed the highest antibody titer. Using a DNA-prime/VACV boost regimen, Cui et al. confirmed that the GP5-Mosaic vaccines conferred protection in pigs against heterologous viruses. Vaccination with the GP5-Mosaic-based vaccines resulted in cellular reactivity and higher levels of neutralizing antibodies to both VR2332 and MN184C PRRSV strains. In contrast, vaccination of animals with the GP5-WT vaccines induced responses only to VR2332. GP5-Mosaic vaccine can induce cross-reactive cellular responses to diverse strains, neutralizing antibodies, and protection in pigs . Jiang et al. obtained the suicide DNA vaccine pSFV-56 co-expressed with ORF5 and ORF6 and reported that it had good immunogenicity and could induce immune animals to produce a greater immune response. Jiang et al. co-expressed GP5 and M proteins of PRRSV and found that the resulting dimer significantly improved DNA immunity. Furthermore, cytokines also improve the body's immune response levels. Qin et al. developed a nucleic acid vaccine PVIR-IL-18-ORF5 containing porcine interleukin-18 (IL-18) and conducted immune experiments in mice. The percentage of CD8-positive cells in the pVIR-IL-18-ORF5 experimental group was significantly higher than that in the pVAX1-ORF5 group, which indicated that IL-18 improved both cellular and humoral immunity in animals, with notable improvement in cellular immunity. Li et al. developed a recombinant plasmid carrying the PRRSV GP5 gene (pVAX-GP5) and porcine interleukin-15 gene (pVAX-IL-15). They inoculated mice with one or both genes and evaluated their humoral and cellular immunity. The proliferation tests showed that the T lymphocyte counts increased in the peripheral blood and spleen of pVAX-GP5-treated mice and were significantly enhanced in combination therapy with pVAX-IL-15. In addition, some studies revealed that adding porcine glutathione peroxidase-1 (GPX1) to PRRSV DNA vaccines produces an adjuvant effect and enhances the humoral and cellular immunity in animals . Recent studies indicate that vaccination with GP5 chimeric DNA vaccine induces cell reaction and high levels of neutralizing antibodies . Although DNA vaccine developments have made great progress, their immune effects are unstable, which warrants further research and improvement. Recent developments in subunit vaccines have attracted much attention. Plana et al. immunized pregnant sows with insect cell expression products of PRRSV ORF3 and ORF5 of the Spanish isolate (Olot/91) alone or in combination. The results showed that the ORF3 expression product had a protection rate of 68.4%, whereas that of the ORF5 expression product was 50%. Therefore, GP3 and GP5 subunit vaccines have good immunogenicity and are good candidate genes for recombinant subunit vaccine development. Yuan et al. studied the immune-enhancing effects of Taishan Pinus massoniana pollen polysaccharides (TPPPS) and Freund adjuvant on PRRSV GP5 subunit vaccines. The results showed that the recombinant PRRSV GP5 protein induced a significant immune response in animals, which was significantly enhanced by the TPPPS adjuvant, with the middle dose showing the strongest effect. Furthermore, some studies have investigated the use of transgenic Arabidopsis plants expressing codon-optimized and transmembrane deleted antigenic proteins (GP4D and GP5D) as candidate antigens, which produce a good immune response in pigs. Plant-derived GP4D and GP5D proteins provide an alternative platform for producing effective PRRSV subunit vaccines . Guo et al. successfully constructed 10 GP5/M expression vectors. Among the 10 tags, the soluble expression effect of maltose-binding protein (MBP) fused with GP5/M protein was the greatest, and a high-purity recombinant protein of MBP-GP5/M was obtained that laid the foundation for follow-up research and mass preparation of PRRSV subunit vaccines. Live vector vaccines express the main immunogenic genes of PRRSV through live viruses, such as adenovirus, fowlpox virus, herpes virus, and pseudorabies virus (PRV). Qiu et al. developed recombinant fowlpox virus expressing PRRSV GP5, M, and GP5-M fusion proteins and carried out immunological tests on mice to evaluate its potential in inducing humoral and cellular immune responses. The results showed that, compared with other groups, the recombinant fowlpox virus expressing GP5-M fusion protein stimulated mice to produce high levels of specific neutralizing antibodies, significantly promoted interferon g (IFN-g) secretion, and induced the proliferation and expression of specific T lymphocytes, indicating significant enhancement of the humoral and cellular immunity. Wu et al. co-expressed GP5 and M proteins of PRRSV with pseudotyped baculovirus containing hybrid cytomegalovirus (CMV) promoter/SFV (Semliki Forest virus) replicon as vector. The immunogenicity of recombinant baculovirus (BV-SFV-5m6) was compared with that of pseudotype baculovirus vaccine (BV-CMV-5m6), in which the expression of GP5 and M was only driven by CMV promoter. In vitro, BV-SFV-5m6 showed that the expression of foreign protein was enhanced. After immunization in mice, BV-SFV-5m6 induced strong GP5-specific ELISA and neutralizing antibodies against homologous and heterologous viruses. Further, Jiang et al. used live attenuated PRV as the vaccine vector to express GP5 and M proteins in different forms to produce recombinant PRV. The immunized mice subsequently produced PRRSV-specific neutralizing antibodies and had a higher lymphocyte proliferation reaction. Zhao et al. used PRV variant XJ and NADC30-like PRRSV strains (CHSCDJY-2019) as parents to construct a recombinant PRV, rPRV-NC56, with gE/gI/TK deletion and co-expression of NADC30-like PRRSV GP5 and M proteins. The results revealed that inoculation of rPRV-NC56 induced specific humoral and cellular immune responses against PRV and NADC30-like PRRSV in mice and protected them from the PRV XJ strain. Furthermore, Cruz et al. expressed GP5 and M proteins of wild-type PRRSV with porcine transmissible gastroenteritis virus as the vector. The findings showed that the vaccinated animals produced faster and stronger humoral and cellular immune responses than unvaccinated animals. 11. Applications of GP5 Protein in Detection Methods At present, there are several detection methods for PRRSV, such as immunoperoxidase monolayer assay to detect PRRS serum antibody, indirect fluorescent antibody assay (IFA), serum neutralization test, and ELISA to detect PRRS antibodies. The immunoperoxidase monolayer assay and IFA are not suitable for large-scale testing as they are subjective, laborious, and expensive; therefore, they are limited to laboratory testing. The serum neutralization test is mainly used to detect neutralizing antibodies produced by PRRSV infection in pigs, but it cannot be used to diagnose acute infectious cases . ELISA has strong specificity, high sensitivity, and low costs, so it is widely used in the detection of PRRSV antibodies. PRRSV GP5 protein has good immunogenicity and can induce the body to produce neutralizing antibodies. Li et al. amplified PRRSV GP5 by RT-PCR, constructed prokaryotic recombinant expression vector (pGEX-6P-GP5), and transferred it into Escherichia coli BL21 (DE3) for induced expression. The expressed protein was purified by the gradient urea method and then used as coating antigen. Thus, an indirect ELISA method for detecting PRRSV antibodies was established. Hou et al. deleted the transmembrane region of GP5 to match the characteristics of the BB0907 strain of HP-PRRSV GP5 and optimized the remaining gene fragments according to the preference of Escherichia coli. Moreover, they constructed the prokaryotic expression vector of the highly expressed GP5 recombinant protein. The indirect ELISA (GP5-ELISA) method for antibody detection of PRRSV GP5 protein was established by optimizing the reaction conditions. Wang prepared the purified recombinant GP5-3m2 protein, used it as the coating antigen, and optimized the indirect ELISA method using the square array test, thereby establishing the PRRSV GP5 indirect ELISA antibody detection method. Li et al. used the gene sequence of NADC30-like PRRSV strain, which is currently widely used as an amplification template in China; comprehensively analyzed the parameters of secondary structural antigen index, antigenicity, hydrophilicity, surface accessibility, and potential neutralizing epitope of structural PRRSV GP5 and M proteins; and selected the corresponding neutralizing epitopes of GP5 and M proteins as the immunogen. By constructing the fusion expression plasmid pET-32a-GP5/M with linker sequence and expressing soluble GP5/M protein in the Escherichia coli expression system, an indirect ELISA method for detecting PRRSV neutralizing antibody in pigs was established. All the above mentioned studies show that indirect ELISA possesses advantages of high sensitivity, strong specificity, and good repeatability. In addition, a new method for PRRSV detection was established. Yang et al. used PCR combined with denaturing high-performance liquid chromatography (DHPLC) to detect PRRSV. Specific primers were designed according to the sequence characteristics of PRRSV GP5, and PCR amplification products were rapidly detected by DHPLC technology. The PCR-DHPLC method established in this study had the advantages of specificity, sensitivity, rapidity, and good repeatability, and could be used for early diagnosis of clinical PRRSV infection and in molecular epidemiological investigations. 12. Conclusions GP5 protein is a highly variable protein in PRRSV, which is the main protective antigenic protein for inducing immunity. GP5 protein promotes virus replication at the early stage of PRRSV infection by downregulating IFN expression; moreover, its N-linked glycan is essential for virus replication in vivo. GP5 and M proteins form the heterodimer GP5-M in virus-infected cells. GP5-M formation may be related to the post-translational modification, transport, and localization of GP5 protein, which is crucial for the assembly, outflow, and virus budding of offspring virions. GP5 protein interacts with PRA and GAPDH in the cytoplasm, thus triggering PRA and endogenous MYH9 to form filament assembly and inhibiting GAPDH from entering the nucleus. In addition, GP5 protein induces apoptosis. For example, GP5 protein expressing PRRSV in mammalian cells using recombinant vaccinia virus provided evidence that the first 119 amino acids form a region that induces apoptosis, whereas the C-terminal region does not. Furthermore, PRRSV detection can be achieved by an indirect ELISA method based on GP5 protein, which possesses high sensitivity, strong specificity, and good repeatability. At present, great progress has been made in the development of new vaccines against PRRSV. However, the immune effect of vaccines is unstable, and the prevention and control of PRRSV are still major concerns that harm the pig industry today. The development of a safer and more effective PRRSV vaccine is needed. Acknowledgments We apologize to all colleagues whose contributions were not discussed and cited owing to space constraints. Author Contributions Q.L.; writing--original draft preparation, Y.Z.; writing--original draft preparation, H.Z.; writing--original draft preparation, Z.Y.; writing--original draft preparation, H.S.: writing--original draft preparation, W.K.; writing--review and editing, M.Z.; funding acquisition, N.W.; funding acquisition. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement All datasets are available in the main manuscript. The dataset supporting the conclusions of this article is included within the article. Conflicts of Interest The authors declare that they have no competing interests. Figure 1 The structural mode of the PRRSV genome. Figure 2 Alignment analysis of amino acid sequence deduced by GP5. Figure 3 Phylogenetic tree of PRRSV based on the ORF5 gene. Figure 4 Interactions between PRRSV GP5 protein and host proteins. Abbreviations: GP5, glycoprotein 5; IFN-b, interferon b; PRRSV, porcine reproductive and respiratory syndrome virus; EGFP, enhanced green fluorescent protein; RFP, red fluorescent protein; MYH9, myosin heavy chain 9; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; ATP5A, ATP synthase subunit alpha; IRF9, interferon regulatory factor 9; NF-kB, nuclear factor kB. animals-13-00813-t001_Table 1 Table 1 PRRSV vaccines on the market. Year Area Vaccine Strain Vaccine Type 1998 USA RespPRRS MLV Attenuated vaccine 1999 USA MLV RespPRRS/Repro Attenuated vaccine 2005 China CH-1a Inactivated vaccine 2006 USA Ingelvac ATP Attenuated vaccine 2006 China R98 Attenuated vaccine 2006 USA Prime Pac Attenuated vaccine 2008 China CH-1R Attenuated vaccine 2008 China TJM-F92 Attenuated vaccine 2011 China JXA1-R Attenuated vaccine 2011 China HuN4-F112 Attenuated vaccine 2018 China GDr180 Attenuated vaccine 2018 China PC Chimeric vaccine Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000247 | Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive source to characterize genetic alterations related to the tumor. Upper gastrointestinal cancers, including gastroesophageal adenocarcinoma (GEC), biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PADC) are poor prognostic malignancies, usually diagnosed at advanced stages when no longer amenable to surgical resection and show a poor prognosis even for resected patients. In this sense, ctDNA has emerged as a promising non-invasive tool with different applications, from early diagnosis to molecular characterization and follow-up of tumor genomic evolution. In this manuscript, novel advances in the field of ctDNA analysis in upper gastrointestinal tumors are presented and discussed. Overall, ctDNA analyses can help in early diagnosis, outperforming current diagnostic approaches. Detection of ctDNA prior to surgery or active treatment is also a prognostic marker that associates with worse survival, while ctDNA detection after surgery is indicative of minimal residual disease, anticipating in some cases the imaging-based detection of progression. In the advanced setting, ctDNA analyses characterize the genetic landscape of the tumor and identify patients for targeted-therapy approaches, and studies show variable concordance levels with tissue-based genetic testing. In this line, several studies also show that ctDNA serves to follow responses to active therapy, especially in targeted approaches, where it can detect multiple resistance mechanisms. Unfortunately, current studies are still limited and observational. Future prospective multi-center and interventional studies, carefully designed to assess the value of ctDNA to help clinical decision-making, will shed light on the real applicability of ctDNA in upper gastrointestinal tumor management. This manuscript presents a review of the evidence available in this field up to date. ctDNA gastrointestinal tumors liquid biopsy cancer precision medicine National Agency of Research (AEI) in the "Juan de la Cierva-Postdoctoral formacion"8FJC2021-046521-I Spanish Association Against Cancer (AECC)CLJUN19010ARAS Government of Navarra in the La Caixa ProgramL.I. financed by National Agency of Research (AEI) in the "Juan de la Cierva-Postdoctoral formacion" (8FJC2021-046521-I); A.H. is supported by the Clinico Junior 2019 scholarship from the Spanish Association Against Cancer (AECC) (CLJUN19010ARAS); A.M. is partially financed by the Government of Navarra in the La Caixa Program. pmc1. Introduction Currently, histotype diagnosis on tumor tissue is the gold standard for tumor characterization and first therapeutic approach guidance. Moreover, tissue analyses are needed to assess the local tumor microenvironment, for example to know the programmed death ligand-1 (PD-L1) status or the tumor-infiltrating lymphocyte (TIL) characterization. For a further tumor genomic characterization, tissue genomic testing in tissue is the gold standard to identify genomic alterations, assess their prognostic value, select patients for matched targeted therapy and monitor their responses. However, tissue-based genomic testing presents important limitations; mainly, it requires an invasive procedure, tissue may not be available depending on tumor location, and it may not recover full tumor heterogeneity . In this scenario, genomic testing in ctDNA arises as a promising strategy to overcome these pitfalls. Importantly, as aforementioned, ctDNA analysis overcomes the limitations of tissue testing in terms of polyclonal heterogeneity and tissue availability; moreover, due to its minimally invasive nature, it allows for repetitive testing, providing real-time information on the tumor biology . Liquid biopsy is the concept of analyzing biologic material derived from tumor cells into bodily fluids. Among different biologic materials found in liquid biopsies, cell free DNA (cfDNA) is fragmented DNA that can originate from, potentially, any cell of the organism. Circulating tumor DNA (ctDNA), is the fraction of cfDNA released from tumor cells and may reflect the genomic as well as epigenomic landscape of the tumor . 2. Technical Aspects of ctDNA Analysis Detailed technical aspects of ctDNA analysis are beyond the scope of this manuscript, and only some important considerations will be highlighted; for further information, readers are referred to recent publications in the field . Two main approaches are used for the detection of genetic alterations in ctDNA. Advanced polymerase chain reaction (PCR)-based techniques are allele-specific approaches that interrogate previously known mutations with high sensitivity . Alternatively, next-generation sequencing (NGS)-based techniques analyze several alterations in a unique experiment, although with lower sensitivity, and they can detect de novo alterations including copy number variations and rearrangements. NGS analyses can focus on a panel of selected genes or perform whole-exome or genome sequencing . Each approach can be complementary and useful depending on the context and purpose of the assay. PCR-based techniques may be more suitable for the detection of a common, previously identified mutation, while NGS techniques cover the entire molecular characterization and over-time tumor clonality of patients receiving targeted therapy . Finally, low-coverage whole-exome or genome sequencing have been employed for the detection of copy number variations (CNVs) . An important technical limitation of ctDNA analysis relates to the low amounts of DNA present in the sample in some settings, preventing detection of present alterations with current methods. In line with this, detection of CNVs and genomic rearrangements in ctDNA with current technologies is also considered suboptimal . Moreover, some tumors, such as primary brain tumors, renal, prostate and thyroid cancers, are regarded as non-shedders and may not be amenable to ctDNA analysis . Finally, blood cells accumulate somatic mutations with age in a process named clonal hematopoiesis of indeterminate potential, which represents a source of false positives in ctDNA analysis . Figure 1 presents the characteristics of genomic testing in tissue and ctDNA of liquid biopsy. In line with this, a recent study that included 1021 patients with different solid tumors revealed that ctDNA sequencing detected a considerable amount of targetable alterations not present in tissue (9% ESCAT-tier I/II, 14% ESCAT-tier III, and 6% ESCAT-tier IV), while in 7% of the patients the alterations were only found in tissue. This study suggests that ctDNA genetic testing can complement and even replace tissue testing . Indeed, the ESMO has recently published their recommendations for genetic testing in ctDNA in several solid tumors , essentially when rapid results are needed and tissue is unavailable. 3. Clinical Applications of ctDNA Analysis in GEC, BTC and PDAC The analysis of ctDNA and its clinical applicability is most advanced in lung, breast and colon cancer. Indeed, accumulating evidence supports the clinical usefulness of this approach at different time points along disease progression, including early diagnosis, detection of minimal residual disease (MRD) after surgery, molecular characterization for selection of targeted therapy, patient prognosis, and monitoring of treatment response and emergence of resistance to targeted therapy in the advanced setting . In the present review, recent advances in the applications and usefulness of ctDNA in upper gastrointestinal cancers, namely, gastroesophageal adenocarcinoma (GEC), biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) will be presented and discussed. Of note, these malignancies represent hard-to-treat cancers with poor prognosis, which would potentially benefit from the implementation of ctDNA analysis in different clinical contexts . Importantly, GEC, BTC and PDAC are usually diagnosed at advanced stages, when no longer amenable to surgical resection. In this context, it is critical to characterize the genomic landscape of the tumor, with the aim of identifying targetable alterations and selecting patients who would potentially benefit from matched targeted therapies . Overall, targeted therapy approaches improve patient survival compared to conventional chemotherapy . Nevertheless, distinguishing the real clinical value of a given genomic alteration remains challenging . Along this line, important scientific societies have proposed guidelines in order to help in the interpretation of the potential clinical utility of genomic alterations in solid tumors . The European Society of Medical Oncology (ESMO) proposed a classification system for genomic alterations based on their clinical evidence of actionability . The ESMO Scale of Actionability of molecular Targets (ESCAT) establishes six progressive levels according to the existence of matched drugs for a given genomic alteration and their reported clinical benefit: from tier I, in which alteration-drug match is associated with improved outcome in clinical trials, to tier IV, where only preclinical evidence of actionability is reported. Tier IV and X mean a lack of clinical benefit or evidence of actionability, respectively . Interestingly, in a study assessing the clinical applicability of this scale that included 552 patients with different solid tumors in the advanced setting, 67% of the patients showed at least one actionable genetic alteration, and 27% of those were treated with a matched therapy. Importantly, patients harboring alterations of a stronger clinical evidence (tiers I and II) and treated with a matched drug showed longer progression-free survival (PFS) compared to those harboring alterations with a weaker clinical meaning (tiers III and IV) . In this scenario, the ESMO has recently reviewed the genetic landscape and recommendations for genetic testing in several tumors in the advanced setting . Focusing on gastrointestinal malignancies, the ESMO recommends genetic testing of specific alterations in GEC (ERBB2 amplifications, MSI-H, and NTRK 1,2,3 fusions), BTC (IDH1 mutations, FGFR2 fusions, MSI-H, and NTRK 1,2,3 fusions) and PDAC (MSI-H and NTRK 1,2,3 fusions) . Similarly, the American Society of Clinical Oncology (ASCO) has recently proposed their Provisional Clinical Opinion (PCO), a panel of recommendations addressing specific clinical questions related to genomic testing in solid tumors. Overall, genomic testing is recommended for tumors with biomarker-based therapeutic indications and multigene testing when more than one targeted therapeutic indication is available . The evidence of the clinical usefulness of ctDNA in GEC, BTC and PDAC is still limited, and prospective multi-center studies are needed in order to shed light on its real clinical applicability in the next future. In the following lines, pan-cancer studies including GEC, BTC and PDAC patients as well as small studies focused on each of the malignancies will be discussed. Analyzing methylation profiles in ctDNA has been proposed as a valuable tool for early cancer diagnosis, as epigenetic changes, mainly methylation, could precede genetic changes. Pan-cancer studies including thousands of patients with different malignancies have proposed cfDNA concentrations or methylation panels with high diagnostic capacities and the ability to distinguish primary tumor sites . In the advanced setting, the SCRUM-Japan GOZILA study assessed ctDNA-based genetic testing utility for targeted-therapy trial enrolment in patients with advanced gastrointestinal cancers (including colorectal carcinoma, GEC, squamous cell carcinoma, BTC and PDAC) and compared its performance to tissue genetic testing. Importantly, ctDNA-based genetic testing shortened enrolment time and improved enrolment rate without influencing response rates . ctDNA could also be used to predict treatment response and monitor relapses. In two proof-of-concept studies assessing ctDNA levels in pan-cancer patients treated with immunotherapy, ctDNA analysis had a prognostic value and could predict responses . Finally, ctDNA analysis has the capability to monitor polyclonal resistance mechanisms arising in targeted therapy-treated patients. A study including 42 patients with advanced gastrointestinal tumors that developed resistance upon targeted therapy identified novel resistance alterations not found in tissue biopsies for 78% of the cases. Importantly, among the 23 patients analyzed at tissue and ctDNA level, tissue biopsy identified multiple resistance mechanisms in 9% of patients, while by ctDNA this percentage rose to 40% . Table 1 summarizes key findings and study designs of selected studies assessing the role of ctDNA in different types of cancer. 4. Gastroesophageal Cancer (GEC) Gastric cancer represents a global healthcare challenge. With an estimated 1,089,103 new cases and 768,793 new deaths in 2020, this tumor type ranks fifth in incidence and fourth in mortality. Further, the gastroesophagogastric junction adenocarcinoma incidence is increasing . GEC, referring to both tumors together, has been historically referred as one unique entity, although it comprises four different molecular subtypes that recognize the well-described interpatient heterogeneity, a major cause of failure of phase II-III clinical trials with targeted therapies . Additionally, variations within the same tumor (intrapatient-intratumoral-heterogeneity) have also been described, from a spatial and temporal perception . In this regard, especially in GEC, ctDNA appears as a novel approach to overcome this obstacle. 4.1. Screening and Diagnosis Except in high-risk East Asian countries (China, Japan and South Korea), there are no population GEC-screening strategies, and most GEC patients are diagnosed with an advanced disease . The first approach to tumor diagnosis and characterization is based on the tissue histotype, and the performance of genetic testing adds value for prognostic and treatment purposes. Multiple (5-8) biopsies should be carried out to ensure enough material for a first and necessary histological and molecular interpretation . Sequencing the tumor tissue also requires an invasive procedure in order to obtain enough tumor cells. In this regard, ctDNA analyses could cover both limitations, i.e., facilitate the invasive procedures and overcome the spatial heterogeneity. Some studies have shown that ctDNA can be detected in patients with GEC more often than in patients with benign pathologies of the stomach or in healthy controls , thus proposing it as a potential non-invasive tool for massive screening. Furthermore, and as mentioned before, the use of DNA methylation patterns for screening purposes has also been also investigated in GEC as in other tumors, although the sensitivity reported is low for early tumor stages . Prospective studies evaluating the potential use of ctDNA for early diagnosis of GEC are currently ongoing in South Korea (NCT04665687), US (NCT04241796) and UK . 4.2. MRD and Recurrence Monitoring For patients with potentially resectable GEC, standard treatment includes peri-operative combination chemotherapy and surgery in Western countries . Adjuvant chemotherapy is indicated regardless of the tumor response to the neoadjuvant treatment, and there is a lack of reliable programs to monitor recurrence . The use of ctDNA to identify GEC patients at risk of recurrence has been limited to small cohorts, varying assays and time points. Different studies have confirmed the association of pre-operative ctDNA levels with different tumor stages , and how the detection of ctDNA in the immediate post-operative period correlates with eventual recurrences . Notably, a subanalysis of 50 patients included in the phase III CRITICS study, which randomized patients to receive pre-operative chemotherapy and surgery plus post-operative chemotherapy vs. post-operative chemoradiotherapy, demonstrated that the presence of ctDNA within nine weeks of surgery predicted recurrence . Additionally, a retrospective analysis of real-world data including 295 patients showed that ctDNA detection at any time point after surgery or during the surveillance period was associated with shorter recurrence-free survival . Currently, there are different ongoing studies prospectively assessing the value of the MRD-ctDNA detection as a key tool for deciding on the adjuvant treatment indication, in patients with GEC (NTC04510285, NCT02674373). 4.3. Metastatic Disease Monitoring Advanced GEC patients show a very poor prognosis with a 5-year relative survival rate of 6%. Treatment with chemotherapy has been shown to improve overall survival (OS) and quality of life, compared to best supportive care alone . For the time being, only two tissue biomarker subpopulations have been identified for targeted treatment: the human epidermal growth factor (HER2)-positive and PD-L1-positive subpopulations, with potential benefit from the addition of trastuzumab and anti-PD1 agents to the first-chemotherapy line of treatment, respectively . As in other tumors, ctDNA detection and sequencing in GEC patients could provide valuable genetic information and allow to follow up on the tumor genomic evolution without the need for serial tissue biopsies. Again, one should recognize the intrinsic limitations related to the analyses of circulating genomics but not local peri-tumor protein expression. One of the largest retrospective studies of GEC patients demonstrated how ctDNA can potentially recover the temporal and spatial molecular heterogeneity, and how temporal changes in the tumor somatic variant allelic frequency (VAF) correlate with prognosis in patients receiving chemotherapy and immunotherapy . These findings have been corroborated by other smaller studies , including the association of basal ctDNA levels with prognosis , and how ctDNA changes over time correlate with response to different treatments . When considering the HER2-positive subpopulation of GEC, the detection of HER2 amplification in ctDNA has been proposed as an optimal tool to overcome the challenge of tumor temporal and spatial heterogeneity, thus being able to predict and monitor responses to anti-HER2 therapies, and to inform about possible mechanisms of resistance . Ongoing observational and interventional studies would probably validate these findings (NTC04520295, NTC03409848). Blood samples from Epstein Barr Virus (EBV)-positive GEC tumors have been analyzed. Although the plasma EBV-DNA load has been identified only in half of EBV-(tissue)-positive cases, it could correlate with response to treatment . Furthermore, detection of FGFR2b amplification in ctDNA has been partially associated with responses to anti-FGFR2b targeted therapies , but not EGFR amplifications . Concerning historical approaches to individual molecular alterations focusing on single targeted therapies, sequencing techniques could lead to a multiplex approach to define the best personalized treatment algorithm, and ctDNA analysis arises as the best approach to follow up on clonal tumor evolution. The VIKTORY trial was an umbrella trial conducted in South Korea, which assigned patients with metastatic GEC to one of 10 phase II molecularly-driven clinical trials for a second-line treatment, depending on eight different tumor biomarkers on tissue-based sequencing, although ctDNA was analyzed at baseline and longitudinally. Patients receiving the biomarker-selected therapy presented prolonged PFS and OS compared with patients receiving conventional treatment, and reduction of ctDNA levels correlated with response to treatment. The PANGEA trial considered the first three lines of treatment, with optimally sequenced chemotherapy plus different monoclonal antibodies, depending on the molecular findings in tissue and ctDNA. Genomic discordance was observed in tissue between primary and metastatic tumors in 35% of patients, with better concordance when comparing results of metastatic tissue and ctDNA. Additionally, tumor changes after a second-targeted line of treatment was identified in 50% of the treated patients. Meeting its primary endpoint of OS, this study again confirms the spatial and temporal heterogeneity of GEC and demonstrates the feasibility and efficacy of molecular approaches. Finally, and from a country approximation, the already mentioned GOZILA initiative performed comprehensive ctDNA sequencing to rapidly screen cancer patients for trial eligibility, including GEC patients; the authors demonstrated that massive ctDNA genotyping unveils the presence of rare molecular targetable alterations in these patients, including tumors harboring neurotropic receptor tyrosine kinase 1 (NTRK1) fusions. The results of these trials highlight the potential clinical utility of ctDNA analysis in selecting patients for personalized treatment. The incorporation of ctDNA analysis as a complement in the comprehensive tumor characterization in the majority of clinical trials in patients with GEC will confirm its real value. Table 2 summarizes key findings and study designs of selected studies assessing the role of ctDNA in GEC. 5. Biliary Tract Cancer (BTC) BTC is a group of heterogeneous malignancies including mainly extrahepatic cholangiocarcinomas (CCA), as well as gallbladder cancer (GBC). The incidence of these tumors is relatively low in western countries, but significantly higher in certain geographic areas such as China and Thailand for CCA, and Chile for GBC. Moreover, the incidence of intrahepatic CCA is increasing worldwide . When possible, surgery is the unique option of cure, although tumor recurrences are frequent. Even though the majority of patients are diagnosed in advanced stages and prognosis remains dismal, identification of distinct patient subgroups harboring unique molecular alterations with corresponding targeted therapies is improving the treatment paradigm of these patients . 5.1. Screening and Early Diagnosis Early diagnosis of BTC is challenging. BTC usually present with unspecific symptoms and can be confused with benign biliary disorders that may also cause biliary stenosis {Valle, 2021, Biliary tract cancer}. In this regard, cfDNA concentration, CNV scores and/or methylation scores analyzed on ctDNA are increased in patients with CCA and/or GBC and serve to distinguish them from healthy controls and patients with benign biliary lesions . Interestingly, in the context of BTC and PDAC, bile arises as a novel source for ctDNA analysis. Several studies have assessed ctDNA in bile collected after endoscopic biliary drainage for early diagnosis and tumor molecular characterization. Overall, ctDNA found in bile is characterized by larger fragments and shows a better correlation with tumor tissue than plasma . Interestingly, bile ctDNA shows promising diagnostic capacities that outperform current diagnostic strategies . However, the procedure to obtain bile is invasive, which prevents its use for repetitive testing. A meta-analysis comparing the diagnostic efficacy of cfDNA analysis in plasma and bile found that ctDNA detection in blood was more sensible than in bile . Nevertheless, the studies included in this meta-analysis measured different cfDNA or ctDNA-related characteristics and were not homogenous in terms of the characteristics of the patients included. 5.2. Metastatic Disease Monitoring As previously mentioned, median OS of patients with advanced disease is poor, and treatment with up to two lines of chemotherapy has shown modest efficacy . Integration of NGS techniques identifying distinct genomic alterations that underlie disease progression has accelerated the treatment paradigm of BTC. Patients with intrahepatic CCA bear genetic alterations in FGFR2 and IDH1 mutations and benefit from matched targeted therapy , while in patients with extrahepatic CCA and GBC ERBB2 amplifications are more commonly identified . Overall, low numbers of patients with BTC have shown benefit from immunotherapy and NTRK-targeted therapy in clinical trials {Valle, 2021, Biliary tract cancer}. Indeed, the ESMO recommends multigene testing in patients with advanced CCA, in order to detect the full picture of targetable alterations . In this line, a study including 327 patients with BTC revealed that patients receiving genetic alteration-matched targeted therapy in the second line showed better survival than patients without targetable alterations. Particularly, survival was better in patients with ESCAT I-II than the ESCAT III-IV alteration . Different studies have assessed the feasibility of ctDNA genetic testing in BTC and compared its performance to tissue genetic testing. Overall, a similar genetic landscape is identified with both approaches, albeit with different concordance levels depending on experiment settings and testing technologies . The largest study in this regard included 1671 patients and detected ctDNA in 84% of them, of whom 44% harbored targetable alterations. This study highlights a good concordance level between ctDNA and tissue NGS, and the advantage of ctDNA in terms of repeated sampling to follow tumor clonality and arising resistance-mechanisms . Another study analyzed genetic alterations in 121 patients by tissue or ctDNA NGS, showing better survival in patients treated with matched targeted therapies than in patients with un-matched treatment . Moreover, this work reported a better concordance of genetic alterations found in ctDNA with metastatic lesions than with the primary tumor, suggesting that novel alterations may arise in metastasis and that ctDNA analysis may be more informative in the selection of patients for matched targeted therapy. In this regard, a recent study reported a lower failure rate with blood genetic testing than with tissue (15.4% of no detectable alterations in blood vs. 26.8% in tissue), insufficient tumor tissue being the most common cause for tissue testing failure. Importantly, ctDNA-based genetic testing could be an alternative in this situation . Of note, another study focused on early-onset BTC revealed a distinct genetic landscape in patients with early-onset BTC compared to older patients . 5.3. Prognosis and Disease Monitoring Additionally, ctDNA analysis holds a prognostic value . Overall, higher VAF of the dominant genetic alteration prior to treatment associates with worse clinical outcomes than PFS or a higher tumor burden . Intriguingly, some other studies report no association between VAF and clinical outcomes . A recent study proposes a CNV score based on plasma ctDNA analysis that is able to predict response to immunotherapy in patients with hepatobiliary malignancies. Among patients treated with immune checkpoint inhibitors, those with lower CNV risk scores had longer OS and PFS than those with high CNV risk scores . Finally, the analysis of ctDNA to detect genetic alterations conferring acquired resistance to targeted therapy has also been assessed in BTC. Two studies have monitored resistance mechanisms in FGFR2-positive-patients treated with FGFR2 inhibitors by serial ctDNA analysis. Importantly, ctDNA was able to identify multiple resistance mechanisms not detected by tissue biopsy, even before detection of progression by radiologic imaging . Table 3 summarizes key findings and designs of selected studies assessing the role of ctDNA in BTC. 6. Pancreatic Ductal Adenocarcinoma (PDAC) PDAC is an aggressive and fatal malignancy. It ranks seventh among cancer deaths worldwide, with an estimated 495,773 new cases and 466,003 deaths in 2020 . Nevertheless, it is much more common in highly developed countries, in which it will probably surpass breast cancer as the third leading cause of cancer death by 2025 . Around 5-10% of PDAC comprise germline alterations, BRCA1/BRCA2 being the most commonly mutated genes , thus identifying a subset of patients with a potential benefit of PARP inhibitors . Finally, the most common driver mutated genes in PDAC are non-druggable, and chemotherapy constitutes the unique therapeutic approach in the metastatic setting . Considering KRAS as the most frequently mutated gene , multigene NGS evaluation could be of interest in those non-mutated cases for targeted treatment considerations . Pan-cancer studies have reported promising results with targeted therapy for PDAC patients with MSI-H and NTRK fusions . 6.1. Screening and Diagnosis Screening for PDAC is not recommended except for those individuals with a family history or presenting several associated conditions . In this sense, due to the unspecific symptoms, PDAC is normally detected in advance stages and only 20% of cases are surgically treatable . The definitive diagnosis needs an invasive procedure ordinarily performed with a fine needle aspiration cytology of the primary tumor, which relies on sufficient tumor tissue for an accurate molecular analysis . The protein cancer antigen (CA) 19.9, which is measured in clinical practice, is commonly increased not only in an advanced stage of disease but also parallel to bilirubin levels, resulting in an unspecific marker with frequent false-positive results and not useful for initial diagnosis . This highlights the importance of finding a reliable marker to detect the disease at early stages. In patients with resectable tumors, the presence of preoperative ctDNA was associated with larger tumor size, lymph node positivity and the presence of microscopic lymphovascular invasion . In this sense, some studies have shown that levels of ctDNA are significantly greater in those patients with PDAC compared with healthy controls but not with chronic pancreatitis . Moreover, it has been observed that both ctDNA detection and the number of somatic alterations are higher in those patients with metastatic disease in comparison with patients with resectable locally advanced or early-stage tumors . 6.2. Prognosis The prognostic value of ctDNA has been assessed in both early and advanced PDAC. Several studies report that the detection of KRAS mutations in ctDNA prior to active treatment or surgery associates with worse survival rates, as well as with certain clinico-pathological features. Particularly, KRAS mutations in ctDNA associates with tumor location in tail and neck, advanced stages, diagnosis of liver metastasis and high numbers of circulating regulatory T-cells . Interestingly, in some studies, detection of KRAS mutations in tissue does not show prognostic significance, while ctDNA-based testing does . Genetic alterations in other genes or ctDNA-related factors may also hold a prognostic value. In this regard, alterations in chromatin-regulating genes are linked to better outcomes while higher ctDNA concentration, ERBB2 mutations or methylation sites in ctDNA associate with worse outcomes . Studies that assess the genetic concordance between ctDNA and tissue biopsy obtained varying results . 6.3. Disease Monitoring Besides its diagnostic properties, ctDNA also serves to monitor patient response in different settings. In resectable PDAC, it has been observed that both neoadjuvant therapy and surgery reduce the levels of ctDNA , and its detection after surgery could be predictive of an early relapse and worse outcome . Indeed, some studies, including small subsets of patients, suggest that detection of MRD by ctDNA analysis can anticipate imaging-based diagnosis of relapse , and it also outperforms the predictive capacities of protein markers such as CA 19.9 . Similarly, in metastatic PDAC, ctDNA analysis during chemotherapy serves as a marker to monitor response, as it associates with worse survival . In this regard, a recent clinical trial assessed the role of ctDNA to monitor responses to second-line treatment based on enzyme administration, showing that ctDNA evolution after treatment correlated with outcomes . Table 4 summarizes key findings and study design of selected studies assessing the role of ctDNA in PDAC. 7. Conclusions and Future Directions Analyses of ctDNA have emerged as a revolutionary tool for the management of patients with cancer over the past decade. Although the gold standard for tumor histotype characterization and first-line therapeutic approaches relies on the analysis of the tumor tissue, ctDNA constitutes an alternative source of tumor-derived DNA when tumor tissue sampling is challenging. In non-small-cell lung cancer, for instance, ctDNA analysis has become part of the armamentarium for treatment decision-making. Of note, ctDNA is unable to define either the tumor histology or the local microenvironment, but it does challenge the genomic testing. Considering upper gastrointestinal malignancies, several studies have shown the utility of ctDNA analysis, although further prospective validation is needed. Advantages over genetic testing in traditional tissue biopsy include the minimally invasive nature of the test and its ability to reveal a more holistic overview of the tumor genomic landscape, thus covering the temporal and spatial heterogeneity of tumor biology. Studies in GEC, BTC and PDAC have shown how liquid biopsy can potentially impact early cancer detection and prognostication in all tumor stages and may identify the progression earlier than imaging techniques. Additionally, in the advanced setting, ctDNA analysis serves as a non-invasive tool for genetic testing and targeted therapy selection as well as for monitoring therapy response, being able to detect multiple resistance mechanisms. With such an amount of evidence, data generated adds convincement to researchers to rely on the potential role of liquid biopsy in these lethal tumors. In the era of personalized medicine, ctDNA analysis in liquid biopsy emerges as a highly valuable paradigm. Nevertheless, most of the studies are still observational and include small cohorts of patients. Future, prospective multi-center and interventional studies, carefully designed to base clinical decision-making on ctDNA results, will unveil the real clinical role of ctDNA analysis for upper gastrointestinal tumors and allow its integration into the therapeutic armamentarium. Author Contributions Conceptualization and design: I.L., A.E.H. and M.A.; Literature review: I.L., A.E.H. and M.A.; writing and revision: I.L., A.EH., V.A., I.H.-G., E.M., D.G., H.A., R.V. and M.A. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Data supporting reported results are the references described above. Conflicts of Interest L.I., H.A.E. and G.D. declare no conflict of interest. A.V. has been involved as a consultant for advisory roles and received speaker honoraria from MSD, Bristol, Lilly, Astra-Zeneca and Pierre-Fabre. H-G.I. has received speaker honoraria from Astra Zeneca. M.E. has been involved as a consultant for advisory roles with Servier, Roche and Merck Sharp. A.H. has been involved as a consultant for advisory roles from Astra Zeneca and for trial coordination from Ferrer Farma. V.R has been involved as a consultant for advisory roles with Servier, Roche and Merck Sharp and has received speaker honoraria from Roche, Amgen, Merck Sharp and Dohme, Astra Zeneca. A.M. has been involved as a consultant for advisory roles with Amgen, BMS, MSD, Lilly and Servier. Abbreviations ASCO American Society of Clinical Oncology BTC Biliary tract cancer CCA Cholangiocarcinoma cfDNA Circulating free DNA ctDNA Circulating tumor DNA ESCAT ESMO Scale of Actionability of Molecular Targets ESMO European Society of Medical Oncology ERBB2 Epidermal growth factor receptor 2 FGFR2 Fibroblast growth factor receptor 2 GBC Gallbladder cancer GEC Gastroesophageal adenocarcinoma MRD Minimal residual disease MSI-H Microsatellite instability--high NGS Next-generation sequencing NTRK Neurotrophic tyrosine receptor kinase OS Overall survival PCR Polymerase chain reaction PDAC Pancreatic ductal adenocarcinoma PFS Progression-free survival VAF Tumor somatic variant allelic frequency Figure 1 Characteristics of genomic testing in tissue and ctDNA of liquid biopsy. Tissue analysis allows for histotyping and tumor microenvironment characterization. Genetic testing in tissue biopsy (left panel) needs an invasive procedure, thus preventing repetitive testing. It may also show high failure rates due to insufficient tumor material and may only represent part of the entire tissue architecture. On the other hand, high DNA quantities are usually extracted, which eases detection of genetic alteration including CNVs and genomic rearrangements. Genetic testing ctDNA (right panel) is minimally invasive, allowing repetitive testing, and can cover full tumor heterogeneity. Nevertheless, low DNA quantities require highly sensitive technologies, CNV and genomic rearrangement detection is still unsatisfactory, and CHIP may lead to false positives. Abbreviations: CNV: copy number variation; ctDNA: circulating tumoral DNA; CHIP: clonal hematopoiesis of indeterminate potential. cancers-15-01379-t001_Table 1 Table 1 Key findings and study design of main studies assessing the role of ctDNA in different types of cancer. Study-Authors Study Population Collection of Blood Sample Technology Key Findings Bettegowda et al. (2014) 21 GEC; 155 PDAC (out of 410 cancer pts) ns PCR-based technology (EGFR pathway genes) - ctDNA detectable in >75% of advanced stage, for localized tumors, ctDNA detectable in 57% GEC and 48% PDAC. Chen et al. (2020) 217 GEC; 52 liver (out of 414 cancers, 191 pre-diagnosis; 223 post-diagnosis and 414 healthy controls) Basal prior to therapy Methylation assay - High sensitivity to detect cancer in post-diagnosis samples (96.5%) and capable to detect cancer even 4 years before diagnosis. Klein et al. (2021) 130 GEC, 63 hepatobiliary and GBC, 135 PDAC (out of 2823 cancer pts and 1254 non-cancer controls) (from CCGA trial) Basal prior to therapy Methylation assay - High specificity (99.5%) and sensitivity (51.5%) for early cancer detection - Sensitivity increased with advanced stages. Zhang et al. (2020) GEC 48; liver 38; PDAC 42 (out of 978 advanced cancer patients) (from: Study 1108, ATLANTIC and Study 10 trials) Basal prior to therapy and during therapy (6-8 weeks after initiation) NGS (73 genes. Guardant360) - High VAF in the basal sample associates with worse clinical outcomes. - VAF reduction during treatment associates with PFS, OS and ORR Parikh et al. (2019) 6 GEC; 4 BTC (out of 42 advanced cancer pts with acquired resistance to targeted therapy) Post-progression to targeted therapy. NGS (73 genes. Guardant360) - ctDNA analysis detect resistance mechanisms not detectable in tissue biopsies in 78% of the cases. - Acquired resistance mechanisms are highly heterogeneous and polyclonal. Nakamura et al. (2020) 260 GEC; 188 CCA; 363 PDAC (out of 1687 advanced cancer pts) Basal prior to therapy NGS (73 genes. Guardant360) - ctDNA based genetic testing for clinical trial enrolment decreases screening time and improves enrolment rate, without impacting clinical outcomes. - ctDNA reveals novel targetable oncogenic alterations. Abbreviations: BTC, biliary tract cancer; CCA, cholangiocarcinoma: ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; GEC, gastroesophageal cancer; NGS, next-generation sequencing; ORR, objective response rate; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; pts, patients; VAF, tumor somatic variant allelic frequency. cancers-15-01379-t002_Table 2 Table 2 Key findings and study design of main studies assessing the role of ctDNA in GEC. Study Study Cohort Technology Key Findings Lan et al. (2017) 428 GEC (out of 855 gastrointestinal cancer pts and 95 healthy donors) qPCR - Higher levels of cfDNA in GEC compared with non-cancer donors. - ctDNA in plasma after surgery positively correlate with recurrence, better than serum biomarkers (CEA). Catenacci et al. (2021) 15 HER2-amplified GEC (out of 80 GEC) (from PANGEA trial) NGS (73 genes. Guardant360) - HER2 baseline spatial heterogeneity. - HER2 conversion over time to anti-HER2 therapies. Qian et al. (2017) 124 GEC; 64 benign gastric disease; 92 healthy donors Alu-based bDNA - GEC present higher levels of cfDNA, compared with non-cancer donors. - cfDNA more sensible than serum markers (CEA, CA 19.9, CA 72.4) for detecting early GEC. Maron et al. (2019) 1630 GEC NGS (73 genes. Guardant360) - Detectable ctDNA in the postoperative period correlates with inferior DFS. - Genomic alterations more frequently detected in ctDNA-NGS than in tissue-NGS (temporospatial heterogeneity). - Temporal changes in VAF correlate with treatment prognosis. - ctDNA-NGS HER2 amplifications in 11.3% (discordance with tumor-NGS); changes correlated with response to anti-HER2 targeted therapies. Ococks et al. (2021) 97 GEC NGS (77 genes. Avenio ctDNA Expanded) - ctDNA in plasma after surgery positively correlates with recurrence. Yang et al. (2020) 46 GEC NGS (1021 genes. Custom) - ctDNA in plasma after surgery positively correlates with recurrence. Openshaw et al. (2020) 40 GEC ddPCR (SNVs) qPCR (SCNAs) - ctDNA in plasma after surgery positively correlates with recurrence. - High ctDNA levels at diagnosis of metastatic disease predicted poor survival Kim et al. (2019) 25 GEC WGS (Sanger sequencing) - ctDNA in plasma after surgery positively correlates with recurrence. Wo et al. (2021) 21 GEC ddPCR - ctDNA in plasma after surgery positively correlates with recurrence. Fedyanin et al. (2020) 42 GEC ddPCR - ctDNA in plasma after surgery positively correlates with recurrence. Leal et al. (2020) 50 GEC (from CRITICS trial) NGS (58 genes. Agilent SureSelect) - ctDNA in plasma after surgery positively correlates with recurrence. Huffman et al. (2022) 295 GEC Personalized multiplex PCR-based NGS assay - ctDNA in plasma after surgery positively correlates with recurrence. Bang et al. (2015) 71 FGFR2b-positive GEC (from SHINE trial) Nanostring (FGFR2 gene expression) - FGFR2 CNV predicts response to anti-FGFR2 inhibitors. Jin et al. (2020) 46 GEC NGS (425-genes) - Temporal changes in VAF correlate with PFS and response rate. Davidson et al. (2019) 30 GEC DNA SCNA sLow-coverage WGS - ctDNA levels prior chemotherapy positively correlate with survival - SCNAs profiles changed during chemotherapy (clonal evolution). Kim et al. (2018) 61 GEC NGS (73 genes. Guardant360) - Changes in ctDNA levels predict response and PFS to immunotherapy (decrease of ctDNA levels correlated with improved outcomes). Chen et al. (2019) 55 GEC WGS (SCNAs) - Copy number instability score correlate with response to treatment (decrease of the score in pts responding to treatment). Wang et al. (2018) 24 HER2-positive GEC NGS (416 genes)--HER2 SCNAs - High concordance of HER2-tissue amplification and HER2-blood SCNAs. - High HER2 SCNA in pts with innate resistance to anti-HER2 therapies. - HER2 SCNAs decrease in pts wit acquired resistance to anti-HER2 therapies. - Feasibility to identify possible mutated genes that confer resistance to anti-HER2 therapies. Wang et al. (2018) 56 HER2-positive GEC NGS (416 genes. Illumina HiSeq 2500) - High concordance with tissue analyses. - Correlation of HER2 copy number with response to anti-HER2 therapies. Shoda et al. (2017) 15 HER2-positive GEC ddPCR-based HER2 copy number - High concordance with tissue analyses; correlation of HER2 copy number with response to anti-HER2 therapies Kim et al. (2018) 32 HER2-positive GEC (phase II study) NGS (73 genes. Guardant360) - Correlation between plasma HER2 copy number and response to anti-HER2 therapies. - Serial ctDNA sequencing demonstrates tumor evolution and change in genomic profile. Qiu et al. (2020) 140 EBV-positive GEC (out of 2760 GEC) Plasma EBV-DNA load - Only 52.1% of EBV-positive GC pts have detectable plasma EBV-DNA - Plasma EBV-DNA levels positively correlate with disease stage. - Dynamic changes on plasma EBV-DNA levels correlates with treatment response. Wainberg et al. (2022) 155 FGFR2b-positive GEC (from FIGHT trial) NGS for FGFR2 amplification; Personal Genome Diagnostics PGDx elio plasma resolve - FGFR2 amplification is biomarker of response to FGFR2 inhibitors. Smyth et al. (2020) 354 EGFR-positive GEC (from REAL3 trial) ddPCR (EGFR) - High concordance between EGFR copy number in tissue and in liquid biopsies (95%). - Plasma EGFR copy number is a (bad) prognostic biomarker, although does not correlate with response. Abbreviations: CA, cancer antigen; bDNA, branched DNA; CEA, carcinoembryonic antigen; cfDNA, cell free DNA; ctDNA, circulating tumor DNA; ddPCR, droplet-based digital polymerase chain reaction (PCR); DFS, disease free survival; EBV, Epstein Barr Virus; GEC, gastroesophageal cancer; NGS, next-generation sequencing; PFS, progression free survival; pts, patients; qPCR, quantitative PCR; SCNAs, somatic copy number alterations; SNVs, somatic single-nucleotide variants; VAF, tumor somatic variant allelic frequency; WGS, whole-genome sequencing. cancers-15-01379-t003_Table 3 Table 3 Key findings and study design of main studies assessing the role of ctDNA in BTC. Study Study Cohort Timing of Sample Collection Technology Key Findings Wang et al. (2021) 29 BTC; 18 benign biliary lesions Basal at diagnosis NGS (low coverage WGS) - ctDNA CNV assay better diagnostic capacity than CA 19.9, combination of ctDNA CNV and CA 19.9 best diagnostic capacity. - Higher CNV burden associated with worse overall survival. Wasenang et al. (2019) 40 early stage CCA; 40 benign biliary lesions Basal at diagnosis Methylation assay - Combination of two methylation markers in ctDNA show good diagnostic capacities. Kumari et al. (2017) 34 GBC; 39 Controls Basal at diagnosis PCR - cfDNA shows good diagnostic capacities to distinguish GBC from healthy controls and from benign biliary lesions (AUC 0.983). Kumari et al. (2019) 60 GBC; 36 controls Basal at diagnosis PCR and methylation assay - cfDNA integrity value increased in GBC compared to controls; no differences in global methylation levels. - cfDNA integrity good diagnostic. Han et al. (2021) 42 BTC Basal prior to therapy ddPCR for KRAS - Bile ctDNA analysis feasible, better concordance between bile and tissue (80%) than between plasma and tissue (42.9%). Arechederra et al. (2022) 68 BTC or PDAC and benign biliary lesions Basal prior to therapy at diagnosis NGS (52 genes. Oncomine focus) - Bile ctDNA feasible, more mutations detected in bile ctDNA than in tissue or plasma. - Better diagnostic capacity than clinicopathological evaluation. Shen et al. (2019) 10 stage II, III and IV BTC Basal prior to therapy NGS (150 genes. Custom) - Bile ctDNA feasible, bile and tissue DNA similar alterations. Kinugasa et al. (2018) 30 stage II, III and IV GBC Basal prior to therapy NGS (48 genes. Custom) - Bile ctDNA feasible, Correlation with tissue 85.7% - Better diagnostic capacity than cytology evaluation Gou et al. (2021) 28 BTC Basal prior to therapy NGS (520 genes. Custom) - Bile ctDNA feasible, better correspondence between bile ctDNA with tissue than plasma with tissue. - Bile ctDNA + CA 19.9 best diagnostic approach. Zill et al. (2015) 26 stage III and IV BTC/PDAC (18 PDAC; 8 BTC) Basal prior to therapy NGS (54 genes. Guardant) - ctDNA analysis is feasible for cancer genotyping, high level of concordance between tissue and ctDNA. - Tissue genetic testing failed in 35% patients; ctDNA was able to identify mutations in 78% of those. Kim et al. (2015) 38 metastatic BTC ns ddPCR (PIK3CA mutations) - ctDNA analysis is feasible for cancer genotyping, total concordance between ctDNA and tissue. Okamura et al. (2021) 121 advanced BTC ns NGS(68-73 genes. Guardant) - ctDNA and tissue genetic testing are feasible for tumor genotyping. - ctDNA concordance assessed for specific genes, better concordance of ctDNA with metastasis than primary tumor. Berchuck et al. (2022) 1671 advanced BTC-(different subcohorts for each analysis) General ns; a subcohort of Basal prior to therapy NGS (70-73 genes. Guardant) - ctDNA analysis is feasible for cancer genotyping, detects alterations in 84% of the patients and targetable alterations in 44%. - High concordance between tissue and ctDNA for IDH1 and BRAF mutations (87% and 100%), low for FGFR2 fusions (18%). - High VAF in pre-treatment ctDNA associates with worse outcomes. Chen et al. (2021) 154 advanced BTC ns NGS (150 genes. Custom) - ctDNA analysis is feasible for cancer genotyping; 94.8% of the patients showed at least one alteration. - Most frequently altered genes similar in tissue and ctDNA. Csoma et al. (2022) 25 BTC 24 months after initial tissue biopsy or surgical resection NGS (67 genes. Archer) - ctDNA analysis is feasible for cancer genotyping; 84% of the patients show some SNV. - Tumor variant burden (number of variants per sample) similar in tissue and ctDNA. Lamarca et al. (2020) 104 advanced BTC ns NGS (70 genes. FoundationOne.) - ctDNA and tissue genetic analysis is feasible for tumor genotyping, high concordance with tissue in FGFR2 and IDH1 genes (100%). - Failure rate higher in tissue than ctDNA (26.8 vs. 15.4%). Ettrich et al. (2019) 24 stage III and IV BTC Basal prior to therapy and serial sampling in a subcohort NGS (15 genes panel. Custom/CeGaT. 710 gene panel) - ctDNA analysis is feasible for tumor genotyping, tissue and ctDNA concordance overall 74% and 92% for intrahepatic CCA. - VAF in ctDNA associates with poorer outcomes. - Chemotherapy changes the ctDNA mutational landscape. Mody et al. (2019) 130 advanced BTC Any time point (ns) NGS (73 genes. Guardant) - ctDNA analysis is feasible for cancer genotyping; 55% of the patients showed at least one targetable alteration. Uson Junior et al. (2022) 67 metastatic BTC with (1st line with platinum chemotherapy) Basal prior to therapy NGS (73 genes. Guardant) - ctDNA holds prognostic value; high VAF in ctDNA is associated with worse overall survival. Lapin et al. (2022) 31 metastatic BTC (IDH matched therapy) Basal prior to therapy, during therapy, at progression NGS (73 genes. Guardant)/ddPCR - ctDNA holds prognostic value; lower variant allele frequency at baseline correlates with longer time to treatment failure. - Emergence of novel mutations at progression. Yang et al. (2021) 187 advanced hepatobiliary 47 HCC, 115 BTC, 5 mixed Basal prior to therapy (ns) NGS including SNVs and CNVs - ctDNA holds prognostic value; lower CNV risk score measured in ctDNA at baseline improved clinical outcome to ICI therapy. Goyal et al. (2017) 3 advanced BTC (FGFR2 matched therapy) Serial sampling during treatment and at progression NGS (Guardant. 70 genes) - ctDNA is able to detect multiple resistance mechanisms not detectable in a single tissue biopsy. Varghese et al. (2021) 8 advanced BTC (FGFR2 matched therapy) Serial sampling during treatment and at progression NGS (129 genes. Custom) - ctDNA is able to detect multiple resistance mechanisms. Abbreviations: AUC, area under the curve; BTC, biliary tract cancer; CA, cancer antigen; CCA, cholangiocarcinoma; cfDNA, circulating free DNA; CNV, copy number variations; ctDNA, circulating tumor DNA; GBC, gallbladder cancer; HCC, hepatocellular carcinoma; ICI, immune checkpoint inhibitor; IDH, isocitrate dehydrogenase; ddPCR, droplet-based digital polymerase chain reaction (PCR); NGS, next-generation sequencing; ns, not specified; PDAC, pancreatic ductal adenocarcinoma; SNV, single-nucleotide variants; VAF, tumor somatic variant allelic frequency. cancers-15-01379-t004_Table 4 Table 4 Key findings and study design of main studies assessing the role of ctDNA in PDAC. Study-Authors Study Cohort Collection of Blood Sample Technology Key Findings Sausen et al. (2015) 77 stage II (10 pts monitoring) At diagnosis NGS (whole exome and 116 genes--custom)/ddPCR (KRAS, BRAP and PIK3CA) - ctDNA detection at diagnosis and post-surgery, predictor of relapse. - ctDNA detected post-surgery 6.5 mo anticipates recurrence detection by imaging. Pietrasz et al. (2017) 135 (8 pts monitoring) Prior first-line chemotherapy and/or after surgery NGS (22 genes. Ion AmpliSeqTM Colon and Lung Cancer Panel v2)/ddPCR (KRAS) - ctDNA associated with grade of tumor differentiation and greater in metastatic (74.7% metastatic vs. 16.6% locally advanced vs. 19% resectable). No correlation with number of metastatic sites. - ctDNA detection correlated with poor OS in advanced stages (6.5 vs. 19 mo). Post-surgery, negative ctDNA associated with longer DFS (17.6 vs. 4.6 mo) and OS (32.2 vs. 19.3 mo). - ctDNA can anticipate progression detection to imagining-based techniques. ctDNA correlated with chemotherapy response. Bachet et al. (2020) 113 metastatic (88 pts first and second cycle) (from phase II trial) Prior first, second and third cycles NGS (22 genes. Ion AmpliSeqTM Colon and Lung Cancer Panel v2) - ctDNA+ at baseline associated with shorter OS (4.6 mo vs. 8.8 mo) and PFS (1.6 vs. 3.3), but not with ORR. Higher tertile of VAF prognostic of OS and PFS. - During monitoring: ctDNA change associated with ORR; disease control better in ctDNA negative and with decrease maximal VAF at baseline. Kinugasa et al. (2015) 75 (discovery cohort with matched tissue) and 66 (validation cohort); 20 healthy and 20 CP Prior to therapy ddPCR (KRAS-mut) - Concordance 77.3% between tissue and ctDNA. KRAS-mut in greater proportion in cases (63-55%) vs. controls (5%) and CP patients (20%). - Survival time was shorter in KRAS-mut vs. KRAS-wild type in serum. Stage of disease, KRAS-mut and p.G12V mutation significant factors for survival in both cohorts. Groot et al. (2019) 59 resectable Prior and post-surgery ddPCR (KRAS-mut) - ctDNA detection prior-surgery associated with clinico-pathological parameters, decreased median RFS and OS. - ctDNA detection prior adjuvant were likely to relapse and had reduced RFS (5 vs. 15 mo). ctDNA+ preceded detection by imaging in 81%. No association between ctDNA and CA 19.9. Cheng et al. (2020) 210 stage III and IV Prior treatment ddPCR (KRAS-mut) - KRAS p.G12V mutation associated with Tregs high levels, no relationship with KRAS p.G12D. - TNM stage, chemotherapy, Tregs, CA 19.9, CA 125 and KRAS associated with OS. Patients with--KRAS p.G12V mutation and high Tregs had worse survival (4.5 vs 8.5 mo). Patel et al. (2019) 112 advance (14 pts resectable tumor) ns for advanced; before or after surgery for resectable patients NGS - ctDNA detectable in 75% of advanced vs. 50% resectable tumors. - Better concordance: between ctDNA and metastatic tissue (72%) than primary tumor (39%). - KRAS-mut and higher levels of ctDNA associated with worst OS (7.4 vs. 11.4 mo and 6.3 vs. 11.7 mo). - 90% of alterations in ctDNA potentially targetable by FDA-approved agents. 73% from advanced had at least one actionable alteration. Pietrasz et al. (2022) 110 locally advanced and metastatic (test cohort) and 255 metastatic (validation cohort) (from PRODIGE 35 and 37 trials) Prior first-line chemotherapy (test cohort) or at inclusion (validation cohort) NGS (22 genes. Ion AmpliSeqTM Colon and Lung Cancer Panel v2)/methylation-ddPCR (HOXD8 and POU4F1) - Methylation at HOXD8 and POU41 genes could be marker of ctDNA. - ctDNA detection in 63.7% from test cohort (95% with liver metastasis vs 56% without metastasis). - ctDNA detection associated with worse OS and PFS. Nakano et al. (2018) 45 stage I-II Prior-surgery and prior-discharge Clamp PCR (KRAS-mut) - KRAS-mut+ after surgery (not before) had shorter DFS and OS vs. KRAS-wild type. KRAS-mut associated with early recurrence. - Change from KRAS-wild type to KRAS-mut after surgery prognostic factor for poor OS. Watanabe et al. (2019) 78 localized, metastatic and recurrent Prior first-line chemotherapy; prior and post-surgery (>=3 serial samples) ddPCR (KRAS-mut)/RASKET (MEBGEN kit) - Concordance KRAS-mut: 94.7% tumor center vs invasion and 90.9% primary tumor vs metastasis. - No association KRAS-mut and CA 19.9 levels before surgery with RFS. - KRAS-mut+ pre-chemotherapy had decreased OS. CA 19.9 no related. - KRAS-mut emergence associated with worse OS (1-year post-surgery) and PFS (within 6 mo of chemotherapy/4.8 vs. 14.9 mo). No changes in CA 19.9. Kruger et al. (2018) 54 locally advanced and metastatic Prior chemotherapy; weekly during 2 mo; and at time of radiological staging and treatment BEAMing PCR (KRAS-mut) - Concordance between plasma and tissue 75% and only in metastatic 79%. - KRAS-mut+ in plasma at baseline correlated with less OS and PFS. - Changes in KRAS-mut were more pronounced and rapid than changes in tumor markers during monitoring. - At 1st month of chemotherapy, correlation between changes in ctDNA and response to treatment, no correlation with protein-based markers. Del Re et al. (2017) 27 locally advanced and metastatic (25 with monitoring) Prior and post 15th day chemotherapy; and at first radiological test ddPCR (KRAS-mut) - No differences in ctDNA metastatic vs. locally advanced, gender, age, site. - At 15th day, patients with increase KRAS-mut had less PFS and disease progression. - KRAS-mut increase associated with less OS. Early mutation does not correlate with tumor response. Abbreviations: CA, cancer antigen; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; CP, chronic pancreatitis; ddPCR, droplet-based digital polymerase chain reaction (PCR); DFS; disease-free survival; KRAS-mut, KRAS gene mutations; MAF, mutant allelic frequency; mo, month; MST, median survival time; NGS, next-generation sequencing; ns, not specified; ORR, objective response rate; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; RFS, relapse-free survival; Tregs, regulatory T-cells. 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PMC10000248 | Black-billed capercaillie (Tetrao parvirostris) was listed as a first-class state-protected animal because it was endangered in China (Category I). This study is the first to examine the diversity and composition of T. parvirostris gut microbiome in the wild. We collected fecal samples from five black-billed capercaillie flock roosting sites (each 20 km apart) in one day. Thirty fecal samples were sequenced with 16S rRNA gene amplicons on the Illumina HiSeq platform. This study is the first to analyze the fecal microbiome composition and diversity of black-billed capercaillie in the wild. At the phylum level, Camplyobacterota, Bacillota, Cyanobacteria, Actinomycetota, and Bacteroidota were the most abundant in the fecal microbiome of black-billed capercaillie. At the genus level, unidentified Chloroplast, Escherichia-Shigella, Faecalitalea, Bifidobacterium, and Halomonas were the dominant genera. Based on alpha and beta diversity analyses, we found no significant differences in the fecal microbiome between five flocks of black-billed capercaillie. Protein families: genetic information processing; protein families: signaling and cellular processes, carbohydrate metabolism; protein families: metabolism and energy metabolism are the main predicted functions of the black-billed capercaillie gut microbiome through the PICRUSt2 method. This study reveals the composition and structure of the fecal microbiome of the black-billed capercaillie under wild survival conditions, and this study provides scientific data for the comprehensive conservation of the black-billed capercaillie. black-billed capercaillie (Tetrao parvirostris) fecal microbiome function prediction high-throughput sequencing National Natural Science Foundation of China32070405 32270444 32200407 32001228 China Postdoctoral Science Foundation2022M711884 Youth Innovation Team of Shandong Universities2022KJ177 Shandong Provincial Natural Science FoundationZR2021YQ22 Shandong Postdoctoral Innovation ProjectSDCX-ZG-202203027 Shandong Province Colleges and Universities Youth Innovation Science and Technology Teams Support Program2021KJ015 This research was funded by the National Natural Science Foundation of China (32070405, 32270444, 32200407, and 32001228), the China Postdoctoral Science Foundation (2022M711884), the Youth Innovation Team of Shandong Universities (2022KJ177), the Shandong Provincial Natural Science Foundation (ZR2021YQ22), the Shandong Postdoctoral Innovation Project (SDCX-ZG-202203027) and the Shandong Province Colleges and Universities Youth Innovation Science and Technology Teams Support Program (2021KJ015). pmc1. Introduction Black-billed capercaillie (Tetrao parvirostris) belong to the family Tetraonidae (distributed in the coniferous forest zone of eastern Asian Russia). However, black-billed capercaillie were listed as in the class of least concern by the International Union for Conservation of Nature (IUCN), and the species was endangered in China and classified as a first-class state-protected animal (category I). According to historical data, the quantity of black-billed capercaillie in northeast China declined by 35.25% between 1970 and 2018 . Black-billed capercaillie live in flocks through the harsh winter, and their night habitat is dominated by arbor forest (larch, birch, poplar) . Black-billed capercaillie can cope with food shortages using predictable browsing and low energy content foods . During the overwintering period (from October to April of the following year), the bud of Scots pine (Pinus sylvestris), Channamu (Pinus koraiensis), Larch (Larix gmelinii), and Asian white birch (Betula platyphylla) are the main constituents of the diets of the black-billed capercaillie . However, there have been few studies on the fecal microbiome of black-billed capercaillie. The gut microbiome can help the host achieve several important biological functions such as digestion , absorption , and the maintenance of the gut steady-state . Bacteroidetes (phylum), Cerea bacillus, and Pseudomonas aeruginosa are significantly enriched in the fecal microbiome of geese, which can digest fiber to provide the energy for the host . The gut microbiome of animals is affected by many factors, including the environment , phylogeny , flocks , and diet . Many studies have focused on the impact of the environment and diet on the gastrointestinal microbiome of different species or the same species. For example, environmental factors affect the alpha and beta diversity of the gut microbial communities of white-crowned sparrows . Noise pollution from urbanization has also significantly changed the gut microbiome and hormone secretion of birds . Based on the cluster analysis and host phylogeny tree, Laviad-Shitrit found that the eco-evolutionary process termed phylosymbiosis may occur between wild waterbird species and their gut microbial community composition . In a broader phylogenetic context, the diet and host phylogeny affect the gut microbial composition of non-passerine birds, with diet being the main influencing factor . In addition, the flight ability can also affect the gut microbiome composition of birds . There have been few studies of the flock factor, and most of them focused on captive environments . Therefore, we raise two scientific questions. First, what is the fecal bacteria composition of black-billed capercaillie? Second, is there any difference in fecal bacteria composition between different wild black-billed capercaillie flocks? In this study, we performed 16S rRNA gene V3-V4 region high-throughput sequencing of the fecal microbiome of black-billed capercaillie. We aim ed to explore the fecal bacteria composition of black-billed capercaillie and the composition differences between five wild flocks. We want to provide a reasonable basis for understanding and protecting black-billed capercaillie. In this article, we first describe the materials and methods used to answer these questions (feces sample collection, bacterial DNA extraction and sequencing, sequence processing, and statistical analyses), then the results of the study (bacterial 16S rRNA gene data, composition of the fecal microbiome, comparison of microbiome for the studied flocks, and the prediction of the gut microbiota function), followed by their discussion and conclusions. 2. Materials and Methods 2.1. Sample Collection The fecal samples of black-billed capercaillie were collected on 1 January 2017, in the Jinhe Forestry Bureau of Genhe City, Inner Mongolia. During the sampling period, the temperature was approximately -30 degC, which ensures the freshness of feces. Before sampling, we found the night-roosting habitat of five black-billed capercaillie flocks using transect method. The distance between night-roosting habitats was of 20 km, ensuring that there is no flock duplication. Six fresh feces samples were collected from the several available habitats. We used alcohol (99%) to wipe the scalpel, which was used to cut across the feces placed on the sterile gloves . We only collected the core of the fecal matter to avoid disturbance from other birds and animals . We used sterile gloves to pick up the feces and placed the fecal samples in a sterile tube. This sampling method is from our published article . All samples were stored at -20 degC during the transit to Qufu Normal University, China. We stored all samples at -80 degC until sequencing. 2.2. DNA Extraction and High-Throughput Sequencing The cetyltrimethylammonium bromide (CTAB) method was used to extract the total DNA and the purity and concentration of DNA were then determined using agarose gel electrophoresis (1%) . We used the polymerase chain reaction (PCR) primers (forward primer: CTACGGGNGGCWGCAG; reverse primer: GACTACHVGGGTATCTAATCC) to amplify the V3-V4 hypervariable regions of bacterial 16S rRNA genes. The PCR amplification volume was 50 mL:5 mL of microbial DNA (5 ng/mL), 25 mL of 2 x Taq PCR Master Mix (0.1 U/mL); 18 mL of double-distilled water (ddH2O); 1 mL of forward primer and reverse primer (10 mM). The PCR amplification conditions were as follows: 1 min at 98 degC for pre-denaturation; 25 cycles of 30 s at 95 degC for denaturation; 30 s at 55 degC for annealing and 30 s at 72 degC for elongation, followed by 5 min at 72 degC for the final extension. The PCR products were detected by electrophoresis with 2% agarose gel. We used Qiagen Gel Extraction Kit (Qiagen, Dusseldorf, Germany) to purify the DNA target strip (400-450 bp). We used a TruSeq PCR-Free DNA Sample PreparationKit (Illumina, San Diego, CA, USA) to generate the sequencing libraries and following the manufacturer's recommendations. We used Qubit 2.0 Fluorometer (ThermoScientific, Waltham, MA, USA) and an Agilent Bioanalyzer 2100 system to evaluate the sequencing library quality. Finally, we used Illumina HiSeq2500 PE250 (San Diego, CA, USA) to sequence the sequencing library. 2.3. Sequence Processing and Statistical Analyses We used Fast Length Adjustment of Short reads (FLASH software; V 1.2.11) to cut the barcode and primer sequences and combined the pair-ended reads. We referred to the tags quality control process of Quantitative Insights into Microbial Ecology (QIIME) pipeline (Qiime; V1.7.0) pipeline and performed the following operations: tags interception and tags length filtering. Based on UCHIME algorithm , the Parallel-Meta Suite (PMS; V 3.7) was used to eliminate chimeric sequences. Based on the sequence similarity at 97%, we performed PMS to cluster the sequences into operational taxonomic units (OTUs). We used vsearch and SILVA ribosomal RNA databases (v 138.1) built into PMS (V 3.7) to annotate each sample, and we then obtained the set of operational taxonomic units (OTUs) relative abundance table and each taxon relative abundance tables for all data. Based on the OTU level, the rarefaction curve, species accumulation boxplot, non-metric multidimensional scaling analysis (NMDS), principal coordinate analysis (PCoA), and Tukey test of beta diversity were plotted using the ggplot2 package in R software (v 4.2.1). The Kruskal-Wallis test of alpha diversities (richness, chao1, and Good's coverage indices) among five wild flocks was calculated using the vegan package of R software (v 4.2.1). Rarefaction curve and Good's coverage index can be used to evaluate whether the sequencing results and depth content meet the requirements of subsequent experiments. The species accumulation boxplot can be used to evaluate whether the sequencing samples are sufficient for analysis. We used PCoA, NMDS, and the Tukey test of beta diversity to verify whether the bacterial compositions of five flocks were different. We used the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) software to predict the gut microbiome functions of black-billed capercaillie. In all figures, we represent the samples of black-billed capercaillie by "HZ" and the five flocks by "F" (F1, F2, F3, F4, and F5). 3. Results 3.1. 16S rRNA Gene Data We obtained 2,190,160 effective tags from 30 black-billed capercaillie samples, with an average of 73,005 (standard deviation, 9509) sequences per sample. The 30 rarefaction curves and species accumulation boxplot became gradually flattened, indicating that the sequencing depth and the number of samples were reasonable for the subsequent experimental analyses. The goods coverage index of all data was higher than 99.6%, suggesting that all sequencing data effectively represent the fecal microbiome of black-billed capercaillie. 3.2. Results for Fecal Microbiome At the phylum level, we used bacteria with >1% abundance in each sample to generate a relative abundance column cumulative plot. Camplyobacterota (33.44%) were the most abundant in the gut microbiome of black-billed capercaillie, and the other fecal dominant bacteria of gut microbiome were Bacillota (25.51%), Cyanobacteria (24.12%), Actinomycetota (14.92%), Bacteroidota (1.46%), and Acidobacteriota (0.26%) . We listed OTUs with an average abundance greater than 1% in Table 1. Among them, six OTUs (OTU_3504_102, OTU_3327_4, OTU_3616_27, OTU_26443_5, OTU_3400_101, and OTU_3616_340) belong to Camplyobacterota, three (OTU_11392_1, OTU_2185_14, and OTU_2184_5) belong to Bacillota, two (OTU_25228_508 and OTU_25228_2257) to Cyanobacteria, and two OTUs (OTU_436_66 and OTU_13901) belong to Actinomycetota. At the genus level, we used the abundance of the top 10 genera to generate a relative abundance column cumulative plot. The Faecalitalea (12.60%, belong to Bacillota) were the most abundant in the gut microbiome of black-billed capercaillie. Escherichia-Shigella (10.67%, belong to Camplyobacterota), Halomonas (5.78%, belong to Camplyobacterota), Bifidobacterium (5.65%, belong to Actinomycetota), and Anaerobiospirillum (3.38%, belong to Camplyobacterota) were the other major genera in the gut microbiome of black-billed capercaillie . The relative abundance of the top 10 bacteria genera occupied more than 38% in the fecal microbiome relative abundance of the black-billed capercaillie. 3.3. Analysis of Differences between the Flocks The richness and chao1 indices can show the alpha diversity of the fecal microbiome, and the Kruskal-Wallis test examined the difference in the alpha diversity of the fecal microbiome of five black-billed capercaillie flocks. The boxplot showed that the indexes of richness (p = 0.42) and chao1 (p = 0.6) were not significantly different between the five wild flocks . Based on the unweighted and weighted unifrac distance, the beta diversity boxplot showed that the fecal microbiome composition of five wild flocks were not significantly different . The NMDS and PCoA also indicated that five wild flocks of black-billed capercaillie were grouped together. The results suggest that the fecal microbiome diversity was not significantly different between the five wild flocks. 3.4. Prediction of Gut Microbiome Function Based on the functional prediction analysis, we predicted the 53 KEGG Level 2 categories. All samples displayed high abundances in KEGG Level2 categories of the following protein families: genetic information processing (15.97%); protein families: signaling and cellular processes (5.58%), carbohydrate metabolism (8.75%), amino acid metabolism (6.64%); protein families: metabolism (6.57%), energy metabolism (4.55%), metabolism of cofactors and vitamins (4.11%), membrane transport (1.35%), and translation (2.87%) . 4. Discussion In this study, we first characterized the gut microbiome and potential functions of black-billed capercaillie using the 16S rRNA gene. The relative abundance of Camplyobacterota, Bacillota, Cyanobacteria, Actinomycetota, and Bacteroidota were the major phyla in gut microbiome of black-billed capercaillie. These results were basically consistent with the previous characterizations of birds' gut microbiome, such as that of Oriental stork (Ciconia boyciana) , Zonotrichia leucophrys nuttalli , and crested ibis (Nipponia nippon) . There was no significant difference in the alpha and beta diversity of the gut microbiome between the five wild flocks. Gut bacterial diversity was generally associated with the food diversity. There may not have been any appreciable variations in the gut microbiota makeup of the five wild flocks due to the same forest environment, analogous vegetation (similar diet), and severely cold temperatures. Camplyobacterota contains the most OTUs with an average abundance greater than 1% and was the most abundant phylum enriched in the gut microbiome of black-billed capercaillie. Camplyobacterota was a highly functionally diverse group of bacteria and related to the functional variability of the gut , and the most abundant phylum in fecal microbiome of many birds . Camplyobacterota can maximize the function of the microbiome while reducing the diversity and mass . This may be beneficial for the black-billed capercaillie to adapt to the buds of various trees (Scots pine, Channamu, Larch, and Asian white birch). The OTU_436_66 and OTU_24538_7 belong to Actinomycetota, which is associated with carbohydrate metabolism . Bacillota contains three highly abundant OTUs: OTU_11392_1, OTU_2185_14, and OTU_2184_5. The food composition of black-billed capercaillie contains fiber and cellulose, and Bacillota contains a lot of fiber-decomposing bacteria and can decompose the fiber and cellulose to provide energy for the host . The highly abundant OTU_25228_508 and OTU_25228_2257 belong to Cyanobacte-ria, which are enriched in the gut microbiomes of passerines . Based on research on the gut microbiome of the American white ibis (Eudocimus albus), it was found that the relative abundance of Cyanobacteria is negatively correlated with urban land cover . n our study, Cyanobacteria was the third-most dominant phylum in the fecal microbiome of the Black-billed capercaillie. We speculate that China's policy of returning farmland to forests has effectively increased its habitat. This policy may prove to be beneficial to in-crease the wild Black-billed capercaillie population. OTU_11392_1 was annotated as Faecalitalea, which is isolated from the feces of chickens, and can produce butyric acid, lactic acid, and formic acid as the main metabolic end products . These acids are important energy substances for the host and maintain host intestinal homeostasis . In our study, the OTU_436_66 in the gut microbiome of black-billed capercaillie was annotated as Bifidobacterium. Complex carbohydrates are the substrate for Bifidobacterium, which are the beneficial bacteria in the host's gut . These two highly abundant bacteria contribute to the energy acquisition and maintenance of gut homeostasis in black-billed capercaillie. Two OTUs were annotated as Halomonas, with a sum of abundances of 3.76%. Halo-monas can balance the cell's osmotic pressure and protect the structures of enzymes, DNA, and the cytomembrane that may improve cell motility, amino acid and carbohydrate metabolism, and the environmental adaptation of the black-billed capercaillie . In our study, OTU_3504_102 was annotated as Escherichia-Shigella, which comprises the dominant bacteria in the gastrointestinal tract microbiomes of newly hatched chicks , Grey catbird (Dumetella carolinensis), and Swainson's thrush (Catharus ustulatus) . In general, Escherichia-Shigella is considered pathogenic bacteria in the animal gut microbiome. For example, Escherichia-Shigella is negatively correlated with the gut microbi-ome alpha diversity and weights of female steppe buzzards . Ralstonia was present as a highly abundant OTU (OTU_26443_5), which uses volatile fatty acids as substrates . Ralstonia acts as a pathogen or opportunistic pathogen in the host . However, we did not conduct metagenomic sequencing analysis and Black-billed capercaillie health assessments. Therefore, we could not determine whether Escherichia-Shigella and Ralstonia are pathogenic bacteria in the gut microbiomes of the Black-billed capercaillie. The predictions of fecal microbiome functions for the Black-billed capercaillie were performed using the PICRUSt2 method . Carbohydrate metabolism, protein families: metabolism, and energy metabolism were the functions found to be highly abundant based on functional prediction analysis. In an environment with a lack of food resources, the predicted fecal microbiome functions were found to be almost consistent among the five wild black-billed grouse flocks. These predicted functions could allow the black-billed grouse to obtain more energy for life activities in the buds of Scots pines (P. sylvestris), Channamu (P. koraiensis), larch (L. gmelinii), and Asian white birch (B. platyphylla). These findings will help us to better understand how the fecal microbiome and metabolism interact. However, as this was not a real metagenomic sequencing analysis, metagenomics and transcriptomics should be analyzed in the future. 5. Conclusions Through 16S rRNA gene sequencing analysis, we characterized the gut microbiome composition of the Black-billed capercaillie and analyzed the differences between flocks. Camplyobacterota, Bacillota, Cyanobacteria, Actinomycetota, and Bacteroidota were the major phyla in the fecal microbiome of the Black-billed capercaillie, and we found no no-table differences in the fecal microbiome compositions, diversity, and predictive functions among different wild flocks. Genetic information processing, signaling and cellular pro-cesses, carbohydrate metabolism, amino acid metabolism, metabolism, energy metabo-lism, and metabolism of cofactors and vitamins were the main functions in the gut micro-biomes of different wild flocks. We hypothesize that the reason for this is the extreme cold conditions and similar tree compositions (same diet) between habitats. These results will help researchers further understand the wild Black-billed capercaillie and contribute to the comprehensive conservation of this endangered species. Acknowledgments We thank the BIG Data Center and National Center for Biotechnology Information for providing the data platform. Supplementary Materials The following supporting information can be downloaded at: Figure S1: The relative abundance column cumulative plot of the predicted KEGG function in each sample. Click here for additional data file. Author Contributions Conceptualization, X.G., X.W. (Xibao Wang) and X.M.; methodology, X.G. and X.W. (Xibao Wang); software, X.W. (Xiaoyang Wu).; validation, X.G., X.W. (Xibao Wang) and Y.S.; formal analysis, W.C. investigation, S.Z.; resources, Q.W., G.S., Y.D. and W.C.; data curation, X.G. and X.W. (Xibao Wang); writing--original draft preparation, X.G. and X.W. (Xibao Wang); writing--review and editing, H.Z.; project administration, H.Z.; funding acquisition, H.Z. All authors have read and agreed to the published version of the manuscript. Institutional Review Board Statement Ethical review and approval were waived for this study, due to the fact that only fecal samples were collected and analyzed. Informed Consent Statement Not applicable. Data Availability Statement The raw data presented from this study can be found in the Genome Sequence Archive in BIG Data Center (accession number, CRA008095; accessed on 7 September 2022) and the Sequence Read Archive in National Center for Biotechnology Information (accession number, PRJNA876315; accessed on 2 September 2022), respectively. Conflicts of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Figure 1 Rarefaction curve plot of 30 black-billed capercaillie samples. In the rarefaction curves, the abscissa is the number of sequencing samples randomly chosen from the sample, and the ordinate is the number of OTUs. Each line represents the gut microbiome of a black-billed capercaillie sample. Figure 2 Species accumulation boxplot. The abscissa is the number of black-billed capercaillie samples, and the ordinate is the number of observed species. The species accumulation boxplot reaches a plateau indicating that the number of OTUs in the community does not increase with an expanding number of black-billed capercaillie samples. Figure 3 Kruskal-Wallis test of fecal microbiome alpha diversity between five wild black-billed capercaillie flocks. The richness and chao1 indices indicate the number of species within the community (higher values indicate higher diversity and richness of the community). The goods coverage index evaluates whether the sequencing results represent the true situation of the fecal bacteria community (the value is close to 1, and the sequencing depth basically covers all species in the sample). The abscissa is the group size and the ordinate is the alpha diversity value. Figure 4 Gut microbiome composition between five wild black-billed capercaillie flocks at the phylum (A) and genus (B) levels. The abscissa represents the black-billed capercaillie samples, and the ordinate represents the relative abundance of fecal bacteria. Figure 5 Comparisons for beta-diversity between five wild flocks based on the weighted (A) and unweighted (B) unifrac distance. The abscissa is the group size, and the ordinate is the unweighted or weighted unifrac distance. Figure 6 Non-metric multidimensional scaling analysis (NMDS) (PCA; (A)) and the principal coordinate analysis (PCoA; (B)) of the fecal microbiome composition. Each point represents the fecal microbiome of a black-billed capercaillie sample. animals-13-00923-t001_Table 1 Table 1 The OTUs with an average abundance greater than 1% and their classification level. OTU Abundance (%) Phylum Class Order Family Genera OTU_25228_508 13.80 Cyanobacteria Oxyphotobacteria Unidentified Unidentified Unidentified OTU_11392_1 12.56 Bacillota Erysipelotrichia Erysipelotrichales Erysipelotrichaceae Faecalitalea OTU_3504_102 10.58 Camplyobacterota Gammaproteobacteria Enterobacteriales Enterobacteriaceae Escherichia-Shigella OTU_25228_2257 9.94 Cyanobacteria Oxyphotobacteria unidentified unidentified unidentified OTU_436_66 5.61 Actinomycetota Actinobacteria Bifidobacteriales Bifidobacteriaceae Bifidobacterium OTU_3327_4 3.37 Camplyobacterota Gammaproteobacteria Aeromonadales Succinivibrionaceae Anaerobiospirillum OTU_3616_27 2.72 Camplyobacterota Gammaproteobacteria Oceanospirillales Halomonadaceae Halomonas OTU_26443_5 2.69 Camplyobacterota Gammaproteobacteria Betaproteobacteriales Burkholderiaceae Ralstonia OTU_13901 2.62 Actinomycetota Coriobacteriia Coriobacteriales Coriobacteriaceae Enorma OTU_3400_101 2.24 Camplyobacterota Gammaproteobacteria Alteromonadales Shewanellaceae Shewanella OTU_24538_7 2.13 Actinomycetota Coriobacteriia Coriobacteriales Atopobiaceae Olsenell OTU_2185_14 1.92 Bacillota Negativicutes Selenomonadales Veillonellaceae Megasphaera OTU_2184_5 1.27 Bacillota Negativicutes Selenomonadales Veillonellaceae Megasphaera OTU_3616_340 1.04 Camplyobacterota Gammaproteobacteria Oceanospirillales Halomonadaceae Halomonas Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000249 | Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve "invasion" to tumors as the component. More and more tumor-nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients. perineural invasion (PNI) tumor microenvironment (TME) single-cell spatial transcriptomics (sc-ST) National Natural Science Foundation of China82171118 This work was supported by the National Natural Science Foundation of China (Grant No. 82171118). pmc1. Background There are three well-known traditional ways for solid tumor metastasis and invasion: direct invasion of surrounding tissue, lymphatic spread, and haematogenic spread . With the deepening of tumor research, the fourth invasion and metastasis mode has gradually attracted the attention of researchers: perineural invasion (PNI). In the process of tumorigenesis, nerves will be induced to sprout into the tumor during tumorigenesis, which in turn leads to cancer-nerve crosstalk, and assists tumor dissemination . PNI was first reported by European scientists who described head and neck cancers that show a tendency to invade along nerves when moving to the intracranial fossa , which is usually associated with poor prognosis and may lead to severe pain, typically pain such as pancreatic adenocarcinoma (PAAD) . Since then, PNI has become the key pathological feature of many malignant tumors, such as PAAD , prostate cancer (PRAD) , colorectal cancer , squamous cell carcinoma (SCC) of head and neck mucosa , adenoid cystic carcinoma (ACC) , etc. As a unique pathological entity, PNI can be observed without lymphatic or vascular invasion. Nerve sheath was composed of three connective tissue layers, which are the epineurium, the perineurium, and the endoneurium . The endoneurium is the innermost layer formed mainly by axons and Schwann cells, and also contains mast cells, resident macrophages, fibroblasts, and blood vessels . A laminated cylindrical layer derived from fibroblasts formed the perineurium to surround the endocardium, and they connected with each other through tight connections and gap connections to form a layer separated by collagen fibers (type IV) . The epineurium is the outermost layer and includes a collagen tissue sheath, a plexus of blood vessels, lymphatic vessels, resident macrophages, fibroblasts, mast cells, and sometimes adipose tissue . The definition of PNI was based on the nerve sheath: the tumor is close to the nerve and involves at least 33% of the circumference of adjacent nerve sheaths, or cancer cells exist in any of the three layers of adjacent nerve sheaths . The incidence of PNI is different among different cancers, such as 70-100% in PAAD , 85-100% in PRAD , 20-57% in colorectal cancer , 25% to 80% in SCC of head and neck mucosa , and up to 80% in salivary adenoid cystic carcinoma (SACC) . Cases reported of PNI were commonly associated with poor prognosis and decreased survival . It has been reported that when PNI occurs in nerves with a diameter of >1 mm, there is an independent correlation between a higher local recurrence rate and PNI . It has also been proved that the difference in the position of the PNI site relative to the tumor will also lead to the difference in patient prognosis . Therefore, some researchers use the term "nerve invasion (NI)" instead of "perineural invasion (PNI)" to describe this tumor behavior. Given the importance of the invasion mode and the extremely serious clinical consequences, researches on this point are essential to control tumor dissemination and monitor disease progression. Although most research focused on the invasion of tumor cells to nerves, recent research reported that PNI starts to include axon growth and possible nerve "invasion" to tumors . More studies have recognized PNI as the result of the interaction of tumor cells, nerve cells, and nerve microenvironment, and all parties work together to promote the invasion of tumors into the space around nerves . The tumor microenvironment (TME) plays an important role in PNI. The interaction of tumor cells, peripheral blood vessels, extracellular matrix (ECM), other non-malignant cells , and signal molecules in TME play key roles in the occurrence, development, and metastasis of cancer . The nerve barrier constitutes a defense line against tumor invasion. When tumor cells invade, peripheral nerve cells release neurotrophic factors, growth factors, chemokines, and cell-adhesion molecules to promote nerve repair and regeneration and maintain the stability of barrier function. At the same time, nerve cells such as Schwann cells and tumor cells interact with each other through autocrine and paracrine signals, enhancing the adhesion between cancer cells and nerves, and promoting tumor diffusion along nerves . All kinds of cells in the microenvironment, including tumor-associated macrophages and fibroblasts, are activated by chemokines to produce peripheral inflammation, release neurotrophic factors, growth factors, and MMPs, and promote the growth, proliferation, and invasion of tumors, resulting in PNI . As our understanding of the pathogenesis of PNI continues to progress, so will the definition of PNI . The study of TME promotes the understanding of the existence and function of nerves in the TME and leads to the emergence of innovative anticancer therapy . Based on the cellular components of TME, we aim to summarize the current theories on the molecular mediators and pathogenesis of PNI and add the latest scientific research progress. The application of some new research methods and technologies may not only find new molecular targets for PNI but also provide valuable insights for the development of PNI in the tumor microenvironment and neural microenvironment; to obtain a better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients. 2. Main Infiltrating cells constituting the tumor matrix include fibroblasts, bone marrow-derived cells (BMDCs), tumor-associated monocytes and macrophages, endothelial cells, endothelial progenitor cells (EPC), myeloid-derived suppressor cells (MDSCs), neurons, T regulatory cells (Treg), and pericytes, and different components in neuroimmune axis and many other unrelated pedigrees, and extra-cellular components . Several populations of BMDCs are recruited into TME and niche, where they can differentiate into tumor-promoting populations, such as EPC, MDSCs, and macrophage-like cells . Factors derived by cells in this microenvironment promote the migration and proliferation of adjacent vascular cells, tumor cells, and neurons, and grow together with tumors . 2.1. Monocytes/Macrophages Monocytes/macrophages are usually the most abundant component in the immune cell population of the TME, and affect tumor progression and metastasis through interaction with tumor cells . The main source of tumor-related macrophages (TAMs) is circulating mononuclear cells, which were derived from myeloid progenitors in the bone marrow and differentiated into mononuclear cells under the mobilization of the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-X-C motif) receptor 2 (CCR2) axis and then enter the peripheral inflammation site through blood or further differentiate into macrophages in primary tumors , and they actively migrate to the tumorigenesis site and rapidly differentiate into TAMs during tumorigenesis, inhibiting various T-cell reactions, maintaining normal tissue homeostasis in response to various systemic infections and injuries, and helping anti-tumor escape . They showed a high degree of functional plasticity, and can rapidly adapt to the disturbance of the environment around them. TAMs were described into M1 and M2 subtypes according to their polarization state . The M1 cell was activated by Th1 cytokine interferon-g (IFN-g), interleukin-12 (IL12), tumor necrosis factor (TNF), and microbial products to exert a tumor-killing effect, while the M2 cell was activated and differentiated by Th2 cytokines (such as IL4, IL5, IL10, IL13, colony-stimulating factor-1 (CSF1), transforming growth factor-1 (TFGb1) and prostaglandin E2 (PGE2) to exert angiogenesis and immunosuppressive effect . Anti-tumor M1 type was recruited at an early stage of tumor development, and the overexpression of the p50 subunit of nuclear factor kappaB (NFkB) in macrophages promoted the repolarization of M1 to M2 , gradually differentiated M1 into a tumor-promoting M2 type . TAMs are generally considered to be M2 macrophages in the TME which, when exposed to hypoxia or lactate, secretes a variety of cytokines with metabolic functions, including IL6, TNF, CCL5, and CCL18 to enhance PNI . TAMs express PD-L1 and can directly reduce the activation of T cells, then suppress the anticancer immune responses . In addition, TAMs can promote tumor progression and invasion by up-regulating matrix metalloproteinases (MMPs) . Carcinoma-produced MMP1 activates neuronal protease-activated receptor 1 (PAR1) and induces substance P (SP) release, activating carcinoma neurokinin 1 receptor (NK1R), which plays a pivotal role in tumor progression and PNI . Macrophage-derived IL-1b induces non-neuronal cells to synthesize nerve growth factor (NGF), and activated macrophages can also release glial cell-derived neurotrophic factor (GDNF)-activated RET receptors to trigger tumor cell migration. Evidence from clinical and experimental studies shows that there is a close relationship between TAM density and cancer cell metastasis in various cancers . In PAAD, inflammatory monocytes (IM) expressing CCR2 can be driven by CCL2 released by Schwann cells at the PNI site to recruit preferentially to the nerve site, then differentiated into macrophages and enhance NI by expressing cathepsin B-mediated process to degrade the protein of nerve bundle membrane . Protein species degraded by cathepsin B contained laminin, fibronectin, and collagen IV , which are important parts of the protective nerve bundle membrane, and its function as a peripheral nerve protective barrier is weakened when it is destroyed . In addition, it has been reported that endoneurial macrophages (EMph) can transform into microglia/macrophage subsets involved in cell defense and peripheral nerve regeneration ; EMph around the nerve invaded by cancer is recruited to the tumor front in response to colony-stimulating factor -1(CSF-1) secreted by the tumor, then activated by tumor, secretes a higher level of GDNF as a chemical attractant of cancer cells, which induces phosphorylation of the transmembrane helper receptor RET in PAAD cells and activation of MAPK and PI3K pathways in downstream cancer cells of the extracellular signal-regulated kinase (ERK), promotes the migration to nerves of cancer cells, and enhances the PNI . In addition, macrophages also regenerate injured nerves by secreting VEGF, which was also used by Schwann cells to guide the growth and migration of nerves for tumor axonogenesis . 2.2. Fibroblasts Cancer-associated fibroblasts (CAFs) are an important subpopulation of fibroblasts to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and mediating tumor-enhancing inflammation and invasion in tumors . The origin of CAFs in TME has not been clarified, while in PDAC and CCA, they are considered to be differentiated from stellate cells , and bone marrow-derived circulating progenitor cells of hematopoietic or mesenchymal lineage were also reported to derive from CAFs . Currently, it is believed that local tissue fibroblasts are activated into CAFs, which account for a large part of the stromal cells in TME and up to 80% of the tumor volume in advanced squamous cell carcinoma of the head and neck (HNSCC) , due to the influence of tumor-derived paracrine factors and cytokines . They are responsible for the synthesis, deposition, and remodeling of most of the ECM in the tumor matrix and are thought to be sources of growth factors that affect paracrine, which affect the growth of cancer cells and have been shown to provide key signals supporting tumor progression and allow a small population of cancer cells to escape treatment . Such as transforming growth factor b (TGF-b) secreted by CAFs induced a fibroblastic response in the surrounding environment to synthesize collagen, stiffen the tissue, and destroy microvascular structure by extensive collagen cross-linking, then the mechanical stress of the connective tissue collapses the nearby blood vessels to promote hypoxia . Under hypoxic conditions, interleukin-6(IL-6) produced by cancer cells induces the activation of Schwann cells and triggers the development of PNI , which is also accompanied by the activation of a series of hypoxia-associated signaling pathways. In addition, a dense structure formed by fibrosis around a cluster of cancer cells in an adenocarcinoma caused internal high and lead to the rupture of glandular structure, simultaneously, the high-density fibers formed a track that contributed to the movement of the cancer cells to overflow and diffuse quickly . By the anisotropic E-cadherin/N-cadher in junction, the frontier CAFs exert the physical force to enable the synergistic invasion of CAFs and cancer cells through a dual mechanism: CAFs pull cancer cells away from the tumor facilitating the invasion of cancer cells, while cancer cells polarize its migration away from the tumor to enhance the diffusion of CAFs . In addition, fibroblasts contribute to Schwann-cell-induced axonal growth and, after nerve injury, ephrin-B on fibroblasts activates EphB2 receptors on Schwann cells, and fibroblasts through the ephrin-B/EphB2 signaling pathway induce Schwann cells to migrate through bridges as dense groups or cords to guide axons through injury site . At the same time, CAFs can regulate the N-cadherin/b-catenin pathway through the production/secretion of the axonal guidance molecule Slit2, affecting the neural remodeling related to glandular catheter adenocarcinoma . On the other hand, CAFs promote cancer invasion by secreting factors that cause cancer cell activation and matrix remodeling. Studies have shown that CAFs exist at the PNI site and the produced inactive matrix metalloproteinase-2(MMP-2) is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP) produced by tumor cells, which degrades extracellular collagen in the perineural niche and promotes the spread of cancer cells in the perineural space . 2.3. Schwann Cells (SCs) Schwann cells are the main cells of peripheral nerves, which wrap the single or multiple axons of peripheral nerves and promote signal transduction . When it is damaged or invaded by tumor cells, the axonal injury may trigger the dedifferentiation and activation of SCs through various pathways . The myelinated SCs are dedifferentiated into "repair SCs" (RSCs) with a demyelinating phenotype. By producing a variety of neurotrophic factors and cell surface proteins, including GDNF, artemin and BDNF, p75 neurotrophic factor receptor (p75NTR), and N-cadherin, remodeling the matrix and releasing pro-inflammatory mediators to change the local signaling environment, the injured SCs can induce macrophages to synergistically remove myelin debris , and guide axonogenesis, participate in axon maintenance and post-injury repair, playing an important role in maintaining axon health and neuron survival, opening the way for subsequent nerve regeneration. In the TME, SCs are thought to drive PNI--cancer cells using normal SCs nerve repair procedures to promote PNI . SCs can directly interact with cancer cells through nerve cell adhesion molecule 1 (NCAM1) to break the connection between cells in the tumor cell cluster, thereby dispersing them into single cells . Contact between SCs and cancer cells induces cancer cell protrusion and guides cancer cells to migrate from the cluster to SCs, thereby promoting the invasion and migration of cancer cells along the nerve . L1 cell adhesion molecule (L1CAM) is overexpressed in SCs adjacent to cancer cells and invaded nerves, which strongly induces cancer cells as a strong chemoattractant by activating MAP kinase signaling, and L1CAM also up-regulates the expression of metalloproteinase -2 (MMP2) and MMP9 in PDAC cells by activating STAT3 and facilitates matrix remodeling along the axon . MMPs secreted by SCs, especially MMP2 and MMP9, enhance the degradation of ECM and provide loose channels for the movement of cancer cells . Schwann cells have also been identified as an important source of TGFb, which can activate SMAD signals that induce migration, invasiveness, and PNI in PAAD cells, increasing the invasiveness of cancer cells . Studies have suggested that before cancer cells migrate to peripheral neurons, SCs migrate to pancreatic or colon cancer cells through the NGF-TrkA-p75NTR signaling pathway, but do not migrate to benign cells, so activated oncogenic SCs are likely to construct a pathway to cancer cells . It has also been proposed in the literature that tumor cells activated SCs by c-Jun, while non-myelinating activated SCs form tumor-activated Schwann cell tracks (TASTs) as active scaffolds, and exert forces on cancer cells to enhance cancer mobility, promote cancer cell migration and invasion, a process similar to their reprogramming during nerve repair, leading to "neurogenesis" of precancerous cells and the periphery of tumor cells . At the same time, SCs were demonstrated to be abundant in the surrounding stroma of the precancerous lesions of PAAD, possibly capable of recruiting immune cells at the PNI site, and macrophages recruited by SCs provided additional and persistent cytokine sources to further enhance neural invasion of tumor cells . In a recent study, SCs activated by tumor produced prostaglandin E, polarized T cells to failure phenotype, leading to tumor-related immunosuppression, and play an important role in tumor-nerve crosstalk . In addition, the differentiation of myoepithelial into SCs may be one of the mechanisms of PNI that occur in SACC2. 2.4. Neurons, Nerve Fibers, and Neurotransmitters The interaction between nerve and cancer cells leads to the relationship of mutual growth promotion via the action of neurotrophic factors (NTFs) from nerve and cancer cells, and the pro-invasive and proliferative characteristics of autonomic neurotransmitters from nerve fibers . Pathological neurogenesis is not only the physiological basis of chronic pain produced by the tumors but also contributes to the PNI . Sensory nerve fibers undergoing pathological sprouting in cancers has been reported, which was driven by NTFs, especially the nerve growth factor (NGF), released from tumors and their associated stromal cells . The expression of NTFs by cancer cells and nerves at the same time implies that cancer cells can make use of the same repertoire of trophic signals as nerves do to develop themselves . In addition, after partial peripheral nerves were injured, the sustained demyelination state of the peripheral nerve relieves the axon of growth inhibition and encouraged nerve sprouting . In a cancer such as PAAD, increased neural density (neural sprouting) and size (neural hypertrophy) occur, compared to normal pancreas innervation . The mutual trophic interaction changes neural distribution in a solid tumor, which makes it more conducive to the exchange of signals between cancer cells and nerves . In another way, it could be explained as the pathological neural plasticity induced by tumor-derived factors . These signals were usually transferred via chemical substances with chemoattractive attributes such as NTFs, neuropeptides, neurotransmitters, and so on, leading to the mutual attraction between tumor cells and nerves, and enhancing cancer cells' chemoattraction and motility. In addition, neurogenesis can also be induced by the recruitment of neural progenitor cells from the central nervous system (CNS), especially from the subventricular zone (SVZ), traveling through the bloodstream attracted by tumor-derived factors . They will colonize in a tumor, and differentiate into functional autonomic neurons to produce adrenergic neurons and release neurotransmitters, and stimulate the growth of the tumor, mainly producing adrenergic neurons and releasing neurotransmitters to enrich the TME . It was also proposed that cancer stem cells can differentiate and acquire an autonomic neuron-like phenotype, which may be able to perform neuron-related functions to influence the progression of tumors . For example, cancer stem cells of gastric cancer and colorectal cancer can differentiate into sympathetic neurons producing tyrosine hydroxylase (TH) and parasympathetic neurons producing vesicular Ach transporter . Studies have shown that in the process of PNI, when PAAD cells are close to neurons and SCs of peripheral nerves, they are attracted by neural components of peripheral nerves and migrate to neurons . Neurotransmitters derived from fibers such as glutamic acid, aminobutyric acid (g-aminobutyric acid), NE, or Ach stimulate the survival, proliferation, and migration of tumor cells . Neurotransmitters regulate the immune-promoting and anti-immune responses and affect the TME through this indirect mechanism . Sympathetic and parasympathetic nerve fibers release norepinephrine (NE) and acetylcholine (ACh) in tumors and lymphatic organs, as well as other neuromodulators, to reduce the anti-tumor immune response . The sympathetic nerve fibers in the tumor are related to the early stage of cancer, and the angiogenesis switch is triggered by adrenergic signals . In the late stage of tumor development, parasympathetic nerve fibers help to stimulate the invasion and metastasis of cancer cells . NE derived from sympathetic nerve fibers activates receptors and activates through PKA/STAT3, which leads to the expression of NGF, MMP2, and MMP9 in PAAD cells, enabling them to migrate and invade and induce PNI . NE can also stimulate the production of IL-6 and activate macrophages in TME, which can promote cancer migration and nerve invasion by releasing GDNF . Parasympathetic nerve fibers release Ach, which inhibits immune response through nicotine receptors, while sensory nerve fibers release substances P and CGRP to activate mast cells and blood vessels . Catecholamine activates the immunosuppressive switch in the TME of lung cancer, causing M1 to M2 macrophages to re-polarize and aggregate M2 polarized macrophages and MDSCs. At the same time, it reduces anti-tumor dendritic cells (DC), which leads to the synthesis and release of IL-10, inhibits immune response, leads to the synthesis and release of VEGF, and promotes angiogenesis . In addition, another b2 Adrenergic-Neurotrophin (NT) loop driven by catecholamine can up-regulate NTs to increase sympathetic innervation and local NE accumulation . 2.5. Neurotrophic Factors, Neuregulins and Neuropeptides Peripheral nerve microenvironment includes neurons, Schwann cells, and microglia/macrophages, which secrete various factors to participate in nerve homeostasis, dendritic growth, and axon germination . Neurotrophic factors (NTFs) are a kind of protein, which play an important role in the development, survival, and apoptosis of neurons. Its members include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NRTN), neurotrophins-3(NT-3), NT-4, NT-5, Artemin, etc, which promotes the growth of neurons and PNI together with receptors . There are two different membrane protein receptors of NTFs, namely the tyrosine kinase receptor Trk(TrkA, TrkB and TrkC), which bind neurotrophins with higher affinity and specificity, and p75 neurotrophic receptor (p75NTR), which binds all neurotrophins with lower affinity and specificity . NTFs interact with the extracellular domains of these two receptors, and transmit the signals related to the survival and apoptosis of nerve cells to the inside of cells, thus regulating the development and apoptosis of cells. When the nerve is subjected to transverse or focal crush injury, the expression of NGF and p75NTR far away from the injured site is rapidly induced . In oral squamous cell carcinoma (OSCC), Trk receptors have been confirmed to be overexpressed: Tropomyosin receptor kinase A (NGF), TrkB (BDNF, NT-4/5), and TrkC (neurotrophins 3, NT3) receptors, TrkC and its ligand NTF3 can promote the proliferation of SCs by inhibiting the formation of myeloid cells in the peripheral nervous system, and TrkC may also participate in PNI by regulating the interaction between SCs and tumor cells . Ovarian cancer cells overexpress TrkB, and BDNF/TrkB can promote the migration and invasion of ovarian cancer cells by affecting myelination during nerve regeneration . Macrophage-derived IL-1b induces non-neuronal cells to synthesize NGF, and tumor cells can also secrete NGF and BDNF to active their Trk receptors to stimulate nerve growth . ACC, a neurotrophic tumor, and BDNF receptor, which promotes the survival and differentiation of axons and nerves, are abundant in the nerves invaded around the tumor. The normal prostate is one of the most abundant sources of NGF outside the nervous system . Malignant prostate epithelial cells were reported to overexpress NGF and BDNF, but also the corresponding TrkB and TrkC receptors, which may be related to the migration of malignant cells, frequently occurs along nerves within the prostate, because it may provide abundant neurotrophins to act as chemoattractive guidance clues for tumor migration . It was also reported that PAAD cells migrate preferentially toward human glial along a GDNF concentration gradient . GDNF promotes the expression of integrin, activates MMP-9, and increases nuclear factor-kB(NF-kB), which affects nerve adhesion and invasion and promotes PNI . By binding to the RET tyrosine kinase receptor, GDNF activates two downstream signaling pathways: the PI3-K-AKT pathway, which is involved in pro MMP-9 expression, and the RAS/RAF-MEK-1-ERK1/2 pathway, which is critical for the activation of MMP-9 . In addition, neurons and their related SCs can also release soluble GFRa1 and GDNF(secreted by nerve macrophages), strongly activate RET in cancer cells and initiate the downstream activation of RAS/ERK, MAPK, JNK, and PI3-K-AKT signaling pathways, cancer cell migration, and PNI effect, and induced migration along the nerve . Artemin sends signals through the Ret/GFRa3 receptor complex, as a member of the GDNF family of ligands . In PAAD, over-expressed neurotrophin (NRTN) and Artemin activate RET tyrosine kinase (TK) by binding their homologous GDNF family receptor -a (GFRa) receptors, promoting cancer cell invasion and neuronal plasticity, and promoting the proliferation of nerve fibers around the tumor . When the tumor volume increases, the pressure on nerve fibers increases and axon neurotrophic factors increase . When an initial damage to the nerves by cancer cell, neurons and/or SCs produce Artemin/GFRa3 to repair the nerves, but the abundance of Artemin attracts further cancer cells to the site of injury, which produces a vicious cycle . Axon injury may trigger the dedifferentiation and activation of SCs by releasing neuregulin (NRG) from the remaining neurons . Neuregulin 1 (NRG1), which is the best studied of several neuregulin genes, can active ErbB receptor tyrosine kinases situated on glial membranes and signal to adjacent glial cells . NRG1 forms is an EGF-like domain, binding to and activating receptors belonging to the EGF family of receptor tyrosine kinases erbB2, erbB3, and erbB4, after which it can produce erbB3/erbB2 or erbB4/erbB2 heterodimers or erbB4 homo-dimers and generate active signaling complexes and active an intracellular kinase domain present on erbB2 and erbB4, which phosphorylates specific tyrosine residues within the cytoplasmic tail of the receptor . Then it leads to the activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI-3K) pathways . A research work about PAAD has reported that nuclear FGFR1 regulates the transcription of NRG1, which generates an autocrine loop through ERBB2/4 to further drive invasion . The expression and rapid release of NRG1 in neurons and their axons can be stimulated by NGF, BDNF, NT-3, and GDNF, which are extremely abundant in tumor microenvironment. NRG1 regulates the proliferation, migration and survival of developing SCs , which was one of the important members in PNI. Tumor-derived factors and inflammatory mediators activate peripheral sensory fibers, resulting in the release of the substance P(SP), a neuropeptide that promotes tumor growth. SP enters the tumor, activates NK1R in cancer cells, and activates growth factor receptor through Src (EGFR, HER2) , and activates the MAPK pathway including extracellular signal-regulated kinases 1 and 2 (ERK1/2), to stimulate mitogenesis, induce cell proliferation, and avoid apoptosis by increasing the mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR , which can also be produced by transactive EGFR and activation of NK-1R/Akt/NF-kB signaling pathway . By these pathways, SP mediate the interaction between cancer cells and nerves, and promote the proliferation, invasion, and neurotropism of cancer cells, and PNI . It was shown that SP promotes PAAD cell clusters gradually migrating to the dorsal root ganglions (DRGs) and SP-induced neurite regeneration extended to the clusters from the DRGs which provides an invasive pathway for the clusters . In addition, neurogenic galanin (GAL) activates the G protein-coupled receptor galanin receptor 2 (GALR2) in tumors to induce NFATC2-mediated transcription of cyclooxygenase-2 and GAL, which causes the crosstalk between nerves and cancer cells . Prostaglandin E2 promotes cancer invasion by promoting the secretion of pro-inflammatory mediators and neuropeptides by tumor cells, GAL released by cancer induces neuritogenesis, facilitating PNI . In addition, GALR2-RAP1-p38MAPK-mediated inactivation of Tristetraprolin(TTP), an RNA-binding protein that promotes decay of transcripts of proangiogenic factors (including IL-6, VEGF, IL-8) , and then induces angiogenesis, which facilitates tumor progression by supplying oxygen and nutrients . 2.6. Chemokines Chemokines play an important role in cell-cell interaction, which may mediate the chemical attraction of neurons and/or SCs to cancer cells. Infiltration of tumor cells into nerves can lead to nerve injury and release CCL, which induces inflammatory reaction of nerve repair, and then induces the migration of cancer cells expressing CCR to injured nerves, and finally promotes the PNI effect . In prostate cancer (PRAD) cells, the expression of CCR2 (the receptor of CCL2) promotes NI, and the expression of CCR2 is closely related to the activity of MAPK and Akt pathways and the migration of cancer cells to chemokine (C-C motif) ligand 2 (CCL2) and DRG . In PAAD, sensory-neuron-derived mediators CXCL10 and CCL21 pass through complementary receptors CXCR3 and CCR7 on tumor cells, activating AKT, MEK, and RAC signaling pathways in tumor cells to mediate migration . CXCL12 derived from PAAD cells can induce SCs to infiltrate the tumor in the early canceration process and promote cancer cells to attract and migrate to the nerves . In addition, the main chemokines include chemokine CCL2 and matrix-derived factor 1 (SDF-1/CXCL12), which induce cancer cell migration under the action of CCR2 and CXCR4 receptors respectively, and can also recruit bone marrow-derived cells (BMDC) and M2 macrophages, and the recruited macrophages secrete GDNF, which can activate RET-GDNF receptor a1 (GFRa1) in cancer cells to promote PNI and the invasion of cancer cells . Nerve-related macrophages accumulate in the nerves invaded by tumor cells along the gradient of CCL2 and CSF-1 recognized by CCR2 and CSF-1R receptors, respectively . Nerve-derived C-X3-C motif chemokine ligand 1 (CX3CL1) and NT-3 further support the interaction between nerve tumors , and the former enhances the adhesion between cancer cells and nerves, while the latter regulates the interaction between SCs and cancer cells . 2.7. Semaphorin As a family of membrane-related or secreted glycoproteins, it was reported semaphorin can participate in axon guidance and regulate cell migration such as WBCs, neurons, and endothelial cells, to attend cancer progression . Axonal guidance was the most important function, Semaphorin family can mediate axonal guidance by combining plexin family members, such as Sema3D and plexin D1 (PlxnD1) , and semaphorin-3A (Sema3A) binding to plexin A1 , and the tripartite complexes formed by semaphorins-3 (Sema3s), plexin receptor and neuropilin coreceptor can also mediate axon guidance and invasion . Besides, there still are some other pathological processes mediated by this combination of the Semaphorin family and plexin family, such as that semaphorin-4D (Sema4D) induce tumor angiogenesis and vascular maturation by binding to the plexin B1 receptor on endothelial cells . They can also have an effect on regulating tumor cell survival, such as Sema3E-PlxnD1 signaling suppressing apoptosis in breast cancer . Over-expression of Semaphorin-4F (Sema4F) in PRAD cells contributes to the communication between nerve fibers and cancer cells and induces the proliferation and migration of PRAD cells . 2.8. Tumor Microenvironment In solid tumors, the rapid growth of tumor tissue, high expansion, and incomplete vascular system in tumor tissue, will lead to insufficient oxygen supply in tumor tissue, and the TME presents overall hypoxia . Due to hypoxia, tumor cells can only metabolize energy through anaerobic glycolysis, which will lead to the accumulation of lactic acid . At the same time, ion-exchange proteins on tumor cell membranes are constantly transporting H+ inside cells to outside cells to avoid self-acidosis . These cellular reactions also caused the PH of the tumor microenvironment to decrease to different degrees, and the overall environment was acidic . In the microenvironment of tumor occurrence and development, hypoxia, and acidity, a lot of apoptosis will occur in tumor tissues and peripheral tissues, releasing cell fragments and chemokines, leading to infiltration of inflammatory cells and secretion of inflammatory factors . At the same time, the occurrence and development of the tumor itself will also trigger the immune response of the immune system, causing inflammatory cells to gather in this area, and triggering a severe inflammatory response . This local microenvironment tumor promotes the growth and infiltration of tumor cells into nerve tissue . It interacts with the perineural environment (nerve cells, glial cells, and their products) to further change the microenvironment and promote PNI . Mitochondrial dysfunction and altered glucose metabolism are considered the typical changes in the tumor microenvironment, and this metabolic change is potentially related to the etiology of nervous system degeneration and nerve injury . Oxidative stress was reported to induce chronic neuroinflammation, which contributes to the functionality switch of astrocytes from neurotrophic to neurotoxic, which can release more lactate to reinforce their energetic support to neurons, although upregulating the detrimental pathway . An important feature of energy metabolism in tumor cells is called the "Warburg effect", which is characterized by heavy dependence on glycolysis and the production of a large amount of lactate . Lactate is easily absorbed and decomposed by tumor cells to produce energy . Lactate can promote tumor invasion and metastasis, play an immunosuppressive role, and promote tumor development by inducing and recruiting immunosuppressive-related cells and molecules . In particular, lactate is abundant in the nervous system, which was provided by myelinating Schwann cells (mSCs) using aerobic glycolysis to support action potentials propagation along axons . In addition, glycogen is indicated to be present in the peripheral nerve, primarily in mSCs . We speculate that this is helpful for the tumor to invade the nerve and obtain a faster spread speed after the tumor invades the nerve. 3. Single-Cell Spatial Transcriptomics (sc-ST) Recently, single-cell RNA sequencing (scRNA-seq) has provided unprecedented resolution for revealing complex cellular events and deepening our understanding of biological systems . However, most scRNA-seq protocols require the complete recovery of cells from tissues and the guarantee of cell survival, which excludes many cell types from the scope of research, and largely destroys the spatial background that could have provided information for cell identity and function analysis. However, the functions of many biological systems, such as embryos, liver lobules, intestinal villi, and tumors, depend on the spatial organization of their cells. In the past decade, high-throughput technology has been developed to quantify gene expression in space, and computational methods can be used to identify genes with spatial patterns and describe the neighborhood in tissues, which is called "spatial transcriptomics (ST)". The emergence of this new technology has improved the spatial resolution and high-dimensional evaluation of gene transcription . Some researchers have used single-cell spatial transcript information (sc-ST) obtained by combining single-cell sequence information with spatial transcriptome technology to decipher cell components in the tumor invasion niche, and its transcription reprogramming and potential crosstalk, so that the resolution of research becomes higher and accurate spatial positioning can be obtained. It is well known that hypoxia, EMT, and inflammation signatures contributed to intra-tumor spatial variations, which led to functional differences in different niches . In a study of skin cancer, the author confirmed that tumor cells showed a collective migration phenotype and strongly expressed cytokine A, which contributed to the spatial organization of the invasive niche of basal cell carcinoma . ST showed that tumor cell subgroups in the hypoxia group changed, and different subgroups showed their location characteristics and different gene markers. Subgroups at the front of invasion showed higher proliferation ability, invasiveness, and response to stress under hypoxia . This tech has been also used to explore the spatial landscape of multiple cell subpopulations in esophageal squamous cell carcinoma (ESCC). A study reported the inter-tumoral heterogeneity of ESCC, which, exploring inflammatory fibroblasts (iCAFs), were mostly clustered in the stromal regions, whereas no difference was found in the distribution of myofibroblast (myCAFs) between cancer and stromal regions . Some specific pathways enriched in iCAF subpopulations may be candidates for future research in the progression of ESCC. Another scRNA-seq analysis study also reported the difference in cells between the primary and metastatic sites of HNSCC. Previous studies have also confirmed that the position of macrophages relative to tumor cells is different in various characteristics . In an experiment in diffuse gastric cancer, fibroblasts, endothelial cells, and bone marrow cells were found to be enriched in the deep layer, and it was found that cell-type-specific clustering further revealed that the transition from the shallow layer to the deep layer was related to the up-regulated enrichment of CCL2 transcript in inflammatory endothelial cells and fibroblasts . ST analysis confirmed that stromal cell clusters located at the front of the tumor invasion were identified, which expressed genes related to hypoxia signal transduction, angiogenesis, and cell migration, which proved that hypoxia signal was involved in the metastasis process of invasive gastric cancer . Another study also testified to this view by sc-ST technique, which showed that tumor cells at the outermost edge responded strongest to their local microenvironment, behaved most invasively, and activated the process of epithelial-to-mesenchymal transition (EMT) to migrate to low-confluence areas, and induced similar phenotypic plasticity in neighboring regions . In a study of oral squamous cell carcinoma (OSCC), the spatial localization of nerves in TME was evaluated and successfully summarized into four types of PNI to provide more detailed and accurate pathological information . For the exploration of the interaction between nerve and tumor, the conventional laboratory methods are limited; we could only observe an averaged biological signal over a large number of cells or conventional description based on morphological layer, so the sc-ST should be used to explain the communication between nerve and tumor cells and provide more exact information of tumor cells and nerve . In future research, we expect to make full use of sc-ST to further explain the phenomenon of a tumor's perineural infiltration, observe its interaction at different spatial points, and explore its mechanism. 4. Conclusions and Future Perceptives A lot of early studies have been carried out to explore the inner pathology process of the perineural invasion of some cancers. Important cells, such as SCs, TAMs, CAFs, and some other related cells have been thoroughly studied or are on the way. However, all of these studies were limited and it appears we cannot go any further at present. In this review, we try to introduce a new technology into this pathology process, single-cell spatial transcriptomics. This technology has been used in some studies of common tumors; we can observe the cell components in tumors and their distribution, and then explore the information that we had no chance to capture before through conventional research techniques. According to some studies that have been reported, we hope we can find some transforming cells with an important effect on the PNI process, such as some special CAFs explored in gastrointestinal cancer and the cell-type-specific clustering characteristics. We are trying to understand PNI with this new technology. Maybe soon, we can find a way to stop PNI and the distant metastases that follow. Author Contributions Conceptualization, Z.C.; software, Z.C.; investigation, Z.C.; data curation, Z.C.; writing--original draft preparation, Z.C.; writing--review and editing, Z.C.; visualization, and supervision, Z.C.; project administration, W.J. and Y.F.; funding acquisition, W.J. and Y.F. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest The authors declare no conflict of interest. Figure 1 A general observation on the invasion of peripheral nerves of tumors. Figure 2 Monocytes/macrophages. The M1 cell was activated by Th1 cytokine interferon-g (IFN-g), interleukin-12 (IL12), tumor necrosis factor (TNF), and microbial products, while the M2 cell was activated and differentiated by Th2 cytokines (such as IL4, IL5, IL10, IL13, colony-stimulating factor-1 (CSF1), transforming growth factor-1 (TFGb1) and prostaglandin E2 (PGE2). TAMs (generally considered to be M2) exposed to hypoxia or lactate secretes a variety of cytokines with metabolic functions, including IL6, TNF, CCL5, and CCL18 to enhance PNI. TAMs express PD-L1 and can directly reduce the activation of T cells, then suppress the anticancer immune responses. TAMs promote tumor progression and invasion by up-regulating matrix metalloproteinases (MMPs). TAMs degrade the protein of nerve bundle membrane by expressing cathepsin B-mediated process. This picture is drawn by Figdraw (www.figdraw.com). Figure 3 Fibroblasts. Local tissue fibroblasts are activated into CAFs, due to the influence of tumor-derived paracrine factors and cytokines. They help with the synthesis, deposition, and remodeling of most of the ECM in the tumor matrix. CAFs secrete TGF-b to synthesize collagen, stiffen the tissue, destroy the microvascular structure, and collapse the nearby blood vessels to promote hypoxia, form a track contributing to the movement, overflowing, and diffusion and of the cancer cells, and exert physical force by the anisotropic E-cadherin/N-cadherin in junction, degrade extracellular collagen and induce migration of SCs through the ephrin-B/EphB2 signaling pathway. This picture is drawn by Figdraw (www.figdraw.com). Figure 4 Schwann cell. The myelinated SCs are dedifferentiated into "repair SCs" (rSCs) with a demyelinating phenotype when it is damaged or invaded. By producing a variety of neurotrophic factors and cell surface proteins to interact with cancer cells, including GDNF, artemin and BDNF, p75 neurotrophic factor receptor (p75NTR), TGFb, and N-cadherin, remodeling the matrix to help the migration of cancer cells, and releasing pro-inflammatory mediators: TGFb, prostaglandin E, to change the local signaling environment, the injured SCs can induce macrophages to synergistically remove myelin debris, and produce (TASTs) as active scaffolds to guide axonogenesis or cancer invasion. This picture is drawn by Figdraw (www.figdraw.com). cancers-15-01360-t001_Table 1 Table 1 Summary of factor function and its mechanism. Factor Family Factors Receptor Mechanisms Functions Neurotrophic factors NGF TrkA Activation of Trk receptors results in either neuronal differentiation or mitogenic stimuli. Transmit the signals related to the survival and apoptosis of nerve cells to the inside of cells, thus regulating the development and apoptosis of cells. Stimulate nerve growth BDNF, NT-4/5 TrkB Affects myelination during nerve regeneration; Promote migration and invasion NT3 TrkC Inhibit the formation of myeloid cells in the peripheral nervous system to promote the proliferation of SCs NRTN/Artemin GFRa Activate RET tyrosine kinase (TK) by binding their homologous GDNF family receptor -a (GFRa) receptors Promote cancer cell invasion and neuronal plasticity; Promote the proliferation of nerve fibers around the tumor; Regulate the interaction between SCs and tumor cells. GDNF GFRa1 Active RAS/ERK, MAPK, JNK, and PI3-K-Akt. Prompt pro-MMP-9 expression and activation of MMP-9 to affect nerve adhesion and invasion; Initiate cancer cell migration, and PNI effect, and induced migration along the nerve; Prompt invasion and metastasis formation; Enhance the expression of integrin. Neuregulins NRG1 ErbB Active MAPK, PI-3K. Increase the gap connection communication between SCs; Adjust the physiological characteristics of SCs, and promote the movement and migration of SCS Neuropeptides SP NK-1R, EGFR, HER2 Active MAPK (including ERK1/2 and P38mapk); Active NK-1R/Akt/NF-kB signal pathway; Transactive EGFR and HER2. Increase MMP-2, MMP-9, VEGF, and VEGFR; Stimulate cell proliferation; Lead to growth; Avoid apoptosis. GAL GALR2 Active MAPK signal pathways and inactive TTP. Promote Prostaglandin E2 generation to promote the secretion of pro-inflammatory mediators and neuropeptides by tumor cells; Promotes cytokine secretion (including IL-6, VEGF, IL-8); Induce angiogenesis and neurogenesis. Chemokines CXCL10, CCL21 CXCR3, CCR7 Active AKT, MEK, and RAC signal pathways in tumor cells Promote cancer cells' invasiveness, migration, proliferation, epithelial-mesenchymal transition; and sensitize sensory nerves; Recruit bone marrow-derived cells (BMDC) and M2 macrophages; GDNF secreted by the recruited macrophages activates RET-GDNF receptor a1 (GFRa1) in cancer cells and promotes the invasion of PNI and cancer cells; Enhance the adhesion between cancer cells and nerves. CCL2 CCR2 Active MAPK, AKT signal pathways. CXCL12 CXCR4/CXCR7 Active AKT, ERK, and sonic hedgehog-dependent pathways; CCL2 CCR2 Active RET-GDNF receptor a1 (GFRa1) in cancer cells. CX3CL1 CX3CR1 CX3CL1 direct contact CX3CR1 to adhere to nerve cells. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). 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PMC10000250 | Uncoupling proteins (UCPs) are identified as carriers of proton ions between the mitochondrial inner membrane and the mitochondrial matrix. ATP is mainly generated through oxidative phosphorylation in mitochondria. The proton gradient is generated across the inner mitochondrial membrane and the mitochondrial matrix, which facilitates a smooth transfer of electrons across ETC complexes. Until now, it was thought that the role of UCPs was to break the electron transport chain and thereby inhibit the synthesis of ATP. UCPs allow protons to pass from the inner mitochondrial membrane to the mitochondrial matrix and decrease the proton gradient across the membrane, which results in decreased ATP synthesis and increased production of heat by mitochondria. In recent years, the role of UCPs in other physiological processes has been deciphered. In this review, we first highlighted the different types of UCPs and their precise location across the body. Second, we summarized the role of UCPs in different diseases, mainly metabolic disorders such as obesity and diabetes, cardiovascular complications, cancer, wasting syndrome, neurodegenerative diseases, and kidney complications. Based on our findings, we conclude that UCPs play a major role in maintaining energy homeostasis, mitochondrial functions, ROS production, and apoptosis. Finally, our findings reveal that mitochondrial uncoupling by UCPs may treat many diseases, and extensive clinical studies are required to meet the unmet need of certain diseases. cancer cachexia uncoupling protein mitochondria muscle atrophy metabolism wasting syndrome adipose tissue wasting This research received no external funding. pmc1. Introduction "Cachexia" is a Latin term meaning wasting or weakness of the body due to a prolonged disease condition. Cachexia is diagnosed in many chronic illnesses such as cancer, AIDS, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), stroke, and chronic kidney conditions . Cancer cachexia can be defined as irreversible weight loss, loss of appetite, and loss of skeletal muscle along with a reduction in fat depots . In the last decade, cachexia has been considered a clinical condition in cancer patients that results in early mortality, resistance to chemotherapeutic treatment, and a substantial decrease in quality of life . In 2011, Fearon et al. published an article focused on the classification and diagnosis of cachexia in different populations . In recent years, much preclinical and clinical research has been conducted to identify the underlying mechanism of cachexia in cancer patients. The main culprits of cancer cachexia are systemic inflammation , host immune response , and host-tumor interaction . Due to the activation of these pathways, there is an increase in catabolic cellular and molecular pathways increasing the energy expenditure of the whole body. The imbalance between catabolic and anabolic pathways leads to the wasting of skeletal muscle and adipose tissues . To date, many interventions have been conducted to target the pathophysiology of cachexia, but they have all failed. Drugs such as cytokine inhibitors, thalidomide, NSAIDs, melatonin, anamorelin, corticosteroids, omega-3 fatty acids, and progesterone analogs showed much less evidence in the amelioration of cachectic conditions in cancer patients . Nutritional supplements and exercise are the only possible choice to treat cachexia, although the results are controversial. To develop a new intervention, there is an urgent need to identify new targets in cancer cachexia pathophysiology. As indicated in , UCPs are present in the inner mitochondrial membrane . Mitochondria have a diverse role in biochemical processes such as the generation of adenosine triphosphate (ATP) through oxidative phosphorylation, involved in several steps of the citric acid cycle, urea cycle, and gluconeogenesis also take place in mitochondria. The outer membrane is permeable toward small molecules, whereas the inner membrane has selective permeability to generate an electronic gradient between the outer and inner membrane for the synthesis of ATP . The main task of the mitochondrion is to regenerate the energy required for the normal functions of the cell and body. The cellular mechanism through which it facilitates the regeneration of energy in a form of ATP is known as the "electron transport chain" (ETC) or "cellular respiration" . We will use the term "ETC" for the rest of the article. As the name suggests, the electron transport chain involves the transfer of electrons through the chain of different complexes ranging from complex I to complex IV. Reduced cofactors, such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2), obtained from oxidized molecules via glycolysis and citric acid cycle, undergo a series of electron transfers. NADH yields three molecules of ATP, while FADH2, which enters into ETC at complex II, yields two molecules of ATP. The transfer of electrons through ETC controls the pumping of H+ ions from the mitochondrial matrix to the intermembrane space, thereby creating a proton gradient. The proton gradient generates energy, which is utilized by ATP synthase to phosphorylate ADP to generate ATP . ETC is not accurate, and the energy liberated from the oxidation of molecules does not convert into ATP; instead, some energy is lost in a form of heat. H+ ions re-enter the matrix independent of ATP synthesis, and this is known as a proton leak . There are two types of proton leak: inducible and non-inducible (basal). Non-inducible or basal proton leak is not regulated by a particular transporter, and the transfer of H+ ions across the membrane is not mediated by UCP. The transfer of H+ ions depends on the composition of fatty acyl present in the inner membrane and the presence of adenine nucleotide translocase. The inducible proton leak is highly controlled, with UCPs playing an important role in this process. The proton gradient created from proton transfer across the inner mitochondrial membrane acts in a supply-and-demand manner. The transfer of electrons through different complexes pumps the proton from the matrix to the inner membrane, while ATP synthase drives the proton from the inner membrane to the matrix to generate ATP . The exact mechanism behind basal proton leak is not yet deciphered. Few studies have enlightened the role composition of inner membrane lipids, mainly fatty acyls. Although only one-third of protons leak through the lipid bilayer , and the majority of proton leak is facilitated by the abundance of adenine nucleotide translocase in the inner membrane, it should be noted that proton leaks are dependent upon the abundance of adenine nucleotide translocase (ANT) and not on their activity. Compared with inducible proton leak, the conductance of proton through ANT is considered negligible, as an abundance of ANT is considered very low in the inner membrane of mitochondria . The inducible proton leak is mainly facilitated by uncoupling proteins . Researchers are now curious to identify the exact role and pathophysiology of UCPs and inducible proton leaks in different diseases. Few studies have been carried out to identify the role of the different types of UCPs in the pathophysiology of different diseases. The role of UCPs in cancer and cachexia is discussed in the current article. 2. Uncoupling Protein 1 Brown adipose tissue (BAT) has been found to be activated in hibernating animals, in small rodents during cold exposure, and in infants at birth. The only role of BAT found in different physiological conditions is to induce thermogenesis. Brown adipose tissues are abundant with mitochondria and small lipid droplets . UCP-1 is the first uncoupling protein found in brown adipose tissue, where it represents 10% of the mitochondrial content and is involved in the thermogenesis process via proton leak. There are two types of adipose tissue in which the expression of UCP-1 was predominantly found: brown adipose tissue and beige adipose tissue. The expression of UCP-1 in brown adipose tissue remains constant even at the basal level, while the expression of UCP-1 in beige adipose tissue depends on the phenotype change from white adipose tissue to beige adipose tissue, the activation of the sympathetic nervous system, and peroxisome proliferator-activated receptor-g (PPAR-g) agonists. However, both types of tissue show an equal level of activation and distribution when stimulated and result in the same level of thermogenic activity . The activation of the sympathetic nervous system in response to overfeeding and cold conditions stimulates BAT, which further activates UCP-1 and initiates non-shivering thermogenesis. The sympathetic nervous system stimulates thermogenesis by activating the classic cAMP pathway, which increases the mitochondrial number and size, activates the transcription and translation of UCP-1 protein, and increases the flow of free fatty acids to the mitochondria for heat generation. Prolonged exposure to a cold environment results in the phenotype change from white adipose tissue to beige adipose tissue, which increases the thermogenic capacity of the body . In the beginning, it was thought that sympathetic stimuli are the only way to stimulate non-shivering thermogenesis, although many other factors, molecules, and hormones are involved in the activation of UCP-1 and further thermogenesis. The activation of UCP-1 is highly dependent upon the environmental temperature. The UCP-1 present in brown adipose tissue is considered a major mediator of thermogenesis under two major stimuli: prolonged cold exposure and overfeeding. Prolonged exposure to cold temperatures results in the activation of the sympathetic nervous system, which facilitates lipolysis in WAT. Free fatty acids are released through the lipolysis process utilized by BAT and beige adipocytes to generate heat by increasing resting energy expenditure. These phenomena raised interest among researchers in the treatment of obesity. Early research work was focused on identifying the role of UCP-1 in the regulation of thermogenesis. However, the preclinical data retrieved from different studies highlight the significant influence of ambient temperature. UCP knockout mice with C57BL/6J background demonstrated resistance to diet-induced obesity at subthermoneutral temperature (20 degC). The possible mechanism behind the resistance was the alternate mechanism that maintains the body temperature. Thus, resistance was quickly reversed at a thermoneutral temperature (27 degC) . A similar type of study also showed that at a thermoneutrality temperature (30 degC), the ablation of UCP-1 in mice resulted in obesity under the influence of a high-fat diet. The reason behind UCP-1 ablation resulting in obesity is that under thermoneutrality conditions, increased metabolism is not required to maintain the temperature, but under subthermoneutrality conditions, thermal stress is present, and the body utilizes either brown fat in the presence of UCP-1 or other mechanisms such as shivering thermogenesis in the absence of UCP-1, so the exact role of UCP-1 in BAT may be masked by other complementary mechanisms . 3. Uncoupling Protein 2 Having a close homology to UCP-1, the exact role of UCP-2 is still debatable. The distribution of UCP-2 had been found in adipose tissue, the central nervous system, the immune system, the kidney, and the brain. Based on its high distribution throughout the body, UCP-2 may have a role in several diseases such as obesity, diabetes, cardiovascular disease, neurodegenerative, and psychological disease . Many research groups have published contrasting results regarding the role of UCP-2 in different diseases. The polymorphism of UCP-2 gene such as -866G>A (rs659366), Ala55Val (rs660339), -5331G>A, exon 8 deletion/deletion, and 45 bp insertion/deletion in 3'UTR results in obesity, type-2 diabetes, and neural tube defects . 4. Uncoupling Protein 3 Discovered in 1997, UCP-3 has been found in the skeletal muscle, the heart muscle, and adipose tissue. Initially, UCP-3 was thought to have a thermogenic effect, as it has a similar homology to UCP-1 . However, unlike UCP-1, which has a life cycle of 30 h , UCP-3 has a very short half-life of 30 min, which makes it difficult for any molecular analysis . A study using UCP-3 knockout (KO) mice revealed that UCP-/- 3 mice did not exhibit thermogenesis problems and did not show obesity. Increased levels of reactive oxygen species (ROS) were identified in UCP-3 KO mice, as well as in UCP-3 Tg mice. Although the role of UCP-3 as an antioxidant has remained controversial due to the lack of data regarding the correlation between UCP-3 and ROS production, UCP-3 is also thought to be involved in b-oxidation . 5. Uncoupling Proteins 4 and 5 Same as other UCP proteins, UCP-4 is thought to be involved in the thermogenesis process in brown adipose tissue, as UCP-4 has a similar homology to other UCPs . Earlier studies have revealed that UCP-4 and UCP-5 are mainly present in the brain . UCP-4 is mainly expressed in neurons, the hippocampus, the cortex, the substantia nigra, the striatum, and the cerebellum , while UCP-5 is expressed in the amygdala, the hippocampus, the mediodorsal and paraventricular thalamic nucleus, and the dorsomedial hypothalamic nucleus . Both UCP-4 and UCP-5 are involved in the uncoupling of oxidative phosphorylation by providing a gateway to H+ ions and reducing oxidative stress and thereby protecting the mitochondria from an overload of oxidative stress . UCP-4 is able to protect mitochondrial depolarization and decrease oxidative stress against MPP+-induced toxicity in SH-SY5Y cells, while another study showed the involvement of UCP-4 in maintaining calcium homeostasis and apoptosis in PC12 cells. UCP-5 is also involved in protecting SH-SY5Y cells from MPP+ and dopamine toxicity by preserving mitochondrial membrane potential and decreasing oxidative stress and ATP levels. These studies highlight the function of UCP-4 and UCP-5 in brain homeostasis and their possible role in neurodegenerative diseases. A study evaluating the role of UCP-2 and UCP-3 in obesity found that the overexpression of UCP-2 and/or UCP-3 resulted in a decrease in fat mass with an increase in LDL cholesterol in mice, thus highlighting the role of UCPs in alleviating obesity . Another study evaluating the role of UCP-1 and BAT in an obesity-resistant 129S mice strain found that the ablation of UCP-1 resulted in obesity even in obesity-resistant mice. That study also highlighted that the expression of UCP-1 increased, having a positive correlation with weight, and UCP-1 may counteract weight gain in mice fed with a high-fat diet and cafeteria diet . Another study demonstrated that the gut microbiota was able to enhance the effect of curcumin by activating UCP-1-dependent thermogenesis, which prevents weight gain in diet-induced obese mice . These studies revealed that the activation of UCPs in WAT and BAT leads to high energy expenditure followed by weight loss. The activation of UCPs in obese individuals plays an important role to halt weight gain but has a detrimental effect during cancer cachexia. Several studies involved in identifying the role of UCPs in cardiovascular complications , neurodegenerative disorders , and kidney diseases found that the activation of UCPs decreases oxidative stress, suppresses inflammation, and induces protective effects. However, in cancer and cancer cachexia, UCPs play a negative role and accelerate cachexia in cancer patients. 6. Role of UCPs in Cancer Warburg et al. found that cancer cells use the glycolysis pathway for energy production even in an aerobic environment. The uniqueness of cancer cells is now known as the "Warburg effect" . According to the phenomena, cancer cells utilize the glycolysis pathway due to defects in mitochondrial respiration. The Warburg effect is one of the important hallmarks of cancer and plays a central role in providing energy to fast-growing and differentiating cancer cells . The study conducted by Negre-Salvayre et al. was one of the first studies to identify the role of UCPs in ROS generation. This study found that UCP-2 was able to decrease ROS production in the mitochondria . Another study found that the formation of tumors in a colon carcinoma mice model lacking UCP-2 resulted in higher ROS production, proliferation, and NF-kB production, and decreased apoptosis. The study concluded that higher ROS levels may contribute to tumor progression in UCP-2-deficient mice. Nevertheless, no tumor invasion was detected, which questions the role of UCP-2 in the tumor microenvironment . Subsequent studies revealed that the low expression or deletion of UCP-2 resulted in increased ROS production in the mitochondria. The activation of UCP-2 may play an important role in decreasing ROS production but has a detrimental effect on cancer because many studies have established that the overexpression of UCP-2 in cancer cells decreases ROS production in cancer cells and helps them to thrive . An in vitro study on human colon cancer, using the HCT116 cell line, showed that the overexpression of UCP-2 protects the cells from apoptosis as well as oxidative stress, while the in vivo data showed resistance to anticancer drugs against HC-16-induced cancer in NCr nu/nu mice . Another study also demonstrated that low UCP-2 levels in lung cancer cells can facilitate STAT3 activation and subsequent ROS generation by a chemotherapeutic agent. This study also showed the role of UCP-2 in cancer cell survival and drug resistance . Another research group demonstrated that gemcitabine-induced UCP-2 mRNA expression, which in turn resists gemcitabine-induced damage to cancer cells, elucidates UCP-2-induced resistance . The upregulation of UCP-3 changes the mitochondrial-induced oxidative stress during hypoxia/reoxygenation in vitro in partial H/R-resistant proximal convoluted tubule (PT) cells. As tumor hypoxic cells accelerate malignancy and drug resistance, targeting UCP-3 may help develop anticancer therapies . Another study showed that UCP-2 expression in cancer cells determined the immunomodulatory function of the tumor microenvironment (TME) and had a direct effect on the survival of cancer cells. The activation of UCP-2 altered the cytokine signaling in an interferon-regulatory-factor-5-dependent manner. UCP-2 activated type-1 dendritic cells and CD8+ T cells and normalized TME. That study concluded that the induction of UCP-2, either through genetic modification or a pharmacological approach, resulted in UCP-2 making melanomas cells prone to programmed cell death via protein-1 blockade treatment and thus led to antitumor effects . These studies found that the expression of UCP-2 is initially suppressed, which allows ROS production by cancer cells, and its overexpression in later stages leads to the inhibition of apoptosis and drug resistance. A clinical trial study revealed that HER2-positive breast cancer patients had overexpressed UCP-2 in tumor samples receiving the trastuzumab drug. Treatment with genipin, a UCP-2 inhibitor, significantly increased the antitumor effect of trastuzumab and increased the apoptosis of cancer cells. This study highlighted the role of UCP-2 as a potential target to overcome drug resistance in HER2-positive breast cancer . Another study showed that mitochondrial uncoupling through the activation of UCPs protects CD133(+) colon cancer cells from ROS generation. This study suggested that the use of genipin with a ROS-inducing agent could be useful to eliminate stem-like colon cancer cells . 7. Pathophysiology of Cancer Cachexia The pathophysiology of cancer cachexia mainly involves higher catabolic signaling compared with anabolic signaling, which leads to a higher energy expenditure of the body. The hypermetabolic state of the body results in the wasting of the skeletal muscle and adipose tissues. Proinflammatory cytokines and other mediators released by the tumor itself into the bloodstream are involved in skeletal muscle and adipose tissue wasting . Although the host immune system is predominantly involved in releasing catabolic mediators in response to the tumor, another important factor is radiotherapy or chemotherapeutic drugs, which cause the activation of danger-associated molecular patterns, thus leading to the activation of cytokines and systemic inflammation . Skeletal muscle wasting is mainly mediated through the autophagy-lysosomal pathway and the ubiquitin-proteasomal pathway . Shreds of evidence have suggested that muscle-specific E3 ubiquitin ligases specifically present in muscle such as MuRF-1 and atrogin-1 are the main culprits of skeletal muscle wasting through activating the proteolysis pathway . The activation of molecular pathways such as NF-kB, p38 MAPK, and STAT3 pathways leads to the overexpression of catabolic proteins such as MuRF-1, MAFBX, and atrogins, which further activates autophagy and the proteasomal pathway for muscle atrophy. The activation of autophagy and the proteasomal pathway mainly depends upon the type of cancer cells and the response of an immune system to it. Mitochondrial alterations are another important factor in the promotion of skeletal muscle wasting. Increased mitochondrial oxidative stress results in the degeneration of the mitochondrial network, and the overexpressed Fis1 gene leads to the autophagy and apoptosis of the skeletal muscle . The role of the mitochondria in skeletal muscle wasting in cachectic conditions has caused the mitochondria to be a potential novel target in treating skeletal muscle wasting . Systemic inflammation is another important mediator of skeletal muscle wasting . Preclinical lines of evidence have found elevated levels of TNF-a and that the blockade of TNF-a with antibodies leads to the alleviation of muscle wasting . TNF-a also contributes to the activation of other cytokines such as IL-1 and IL-6, which accelerate skeletal muscle wasting . TNF-a and IL-1 further activate the classic NF-kB signaling pathway. The activation of the NF-kB pathway leads to the activation of the ubiquitin-proteasomal pathway through the overexpression of E3 ligase genes atrogin-1 and MuRF1 . NF-kB also inhibits the Akt pathway, which leads to increased FOXO activity, further activating ALP-related genes (LC3 and Bnip3) . NF-kB also inhibits myogenesis-related genes such as MyoD, Myf5, and MRF4 and decreases myoblast differentiation . The leukemia inhibitory factor (LIF) secreted by tumors belongs to the IL-6 family and has been reported to induce muscle atrophy in animal models. The immunological inhibition of LIF resulted in reduced skeletal muscle loss, thus confirming LIF's role in cancer cachexia . LIF is also involved in lipolysis and lipid catabolism by acting on adipocytes as well as the hypothalamus . Parathyroid-related protein (PTHrP)m, along with other tumor-derived factors, causes severe skeletal muscle loss by increasing the activity of atrophy-related genes . Another important complication in cancer cachexia is the loss of adipose tissues . Adipose tissues are mainly known to be involved in the storage of excessive fat. However, many other functions are reported in the last few decades. One of the important functions is the browning of white adipose tissues. Many studies have reported the browning of adipose tissue during prolonged cold exposure. The study conducted by Wagner et al. reported a phenotype change from white adipose tissue (WAT) to brown adipose tissue in cachectic patients , while another study conducted by Patsouris et al. observed a WAT-to-BAT phenotypic change in burn patients . This study concluded that the WAT-to-BAT change occurs during a hypermetabolic state irrespective of pathological conditions. During cancer cachexia, the tumor and host-derived factors lead to a phenotypic change from WAT to BAT. The activation of BAT leads to more heat production by the mitochondria through upregulating UCPs and thereby increasing the total energy expenditure of the body . During cachectic conditions, the tumor and host-derived factors, such as inflammatory cytokines, catecholamine, the leukotriene inhibitory factor (LIF) , and parathyroid-hormone-related protein (PTHrP) , lead to an increase in lipolysis in adipocytes, which results in increased liberation of free fatty acids in the circulation. These FFAs are taken up by beige or brown adipocytes and utilized to generate excessive heat . 8. Role of UCPs in Cachexia UCPs play a central role in inducing thermogenesis in humans, thereby increasing the energy expenditure of the body. One of the key features of cachexia is higher resting energy expenditure and thereby causing the atrophy of skeletal muscle and draining the adipose tissue. The involvement of UCPs in cancer cachexia was identified in different studies. 8.1. The Role of UCPs in Skeletal Muscle Wasting As discussed above, the primary role of UCPs is to induce non-shivering thermogenesis. The upregulation of UCPs in the skeletal muscle during cancer progression is poorly understood. In one of the early studies, Sanchis et al. demonstrated that the rats bearing Yoshida Ah-130 ascites hematoma showed overexpression of UCP-2 and UCP-3 in the skeletal muscle after tumor induction. The study concluded that the overexpression of UCP-2 and UCP-3 in the skeletal muscle was due to the anorexia induced by the burden of the tumor. This was the first study highlighting the role of UCPs in cachectic conditions during cancer . However, the same researchers further demonstrated contradictory results and showed that anorexia and high circulating FFAs were not directly linked with the activation of UCPs in an LLC tumor model . Another study found decreased TCA cycle flux and ATP synthesis rate in Lewis lung carcinoma (LLC)-bearing mice compared with the normal control. The same study also found the overexpression of UCP-3, atrogin-1, FOXO3a, and PDK4 genes. The study reported that the overexpression of UCPs and mitochondrial uncoupling might be involved in the wasting of the skeletal muscle . Mitochondrial alterations and impairment were observed in tumor-bearing cachectic mice. A previous study demonstrated that mitochondrial alterations led to muscle atrophy in LLC-bearing mice. In C26 tumor-bearing mice, the overexpression of the genes related to proteolysis, autophagy, and mitophagy was associated with decreased mitochondrial fusion proteins. Decreased levels of respiratory complexes I and II was observed in the muscle of tumor-bearing mice, which may be induced by increased levels of BNIP3-mitochondria (SDHa) colocalization. Previous studies also confirmed the downregulation of MFN2 and OPA1 in the atrophied muscle, which leads to altered mitochondrial function and muscle atrophy . Another study showed a lower mitochondrial respiration rate and reduced mitochondrial coupling and found lower mitochondrial protein abundance in the soleus muscle of C26 tumor-bearing mice . These studies showed that in cancer-bearing mice, the induction of the wasting of the skeletal muscle was due to a decrease in mitochondrial function, and the overexpression of UCPs was not the sole contributor to skeletal muscle loss. The same conclusion was drawn by another study conducted on Berlin-Druckrey IX rats with peritoneal carcinosis (PC), which showed that cancer cachexia was able to induce alteration in mitochondrial biogenesis and bioenergetics in skeletal muscles. The study found that alterations in mitochondrial activity were not due to the wasting or browning of AT but due to a decrease in the activity of complex IV, which resulted in decreased oxidative phosphorylation. This resulted in decreased ATP production in the mitochondria of the skeletal muscle. The overexpression of UCP-2 in the skeletal muscle was not associated with the wasting of the skeletal muscle. The overexpression of UCP-2 in quadriceps muscles did not change ROS production in PC rats compared with healthy pair-fed rats . These studies showed that the overexpression of UCPs was found in the skeletal muscle during cancer progression. However, their direct involvement in the wasting process is still debatable, and other factors, such as mitochondrial dysfunction due to autophagy, mitophagy, decreased protein synthesis, and decreased activity of mitochondrial complexes, may be involved in skeletal muscle wasting during cancer. 8.2. The Role of UCPs in Adipose Tissue Wasting Wagner et al. revealed that the browning of WAT starts at the early stage of cachexia and contributes to more energy expenditure and lipid mobilization. Increased energy expenditure is associated with increased mitochondrial activity and uncoupling mechanism in adipocytes. The thermogenic capabilities of interscapular BAT and subcutaneous WAT were found to be increased. The overexpression of UCPs and the browning of WAT contribute to increasing wasting in cancer conditions. Increased UCP-1 staining in the adipose tissue of cancer cachectic cancer patients showed that increased UCP activity was associated with more thermogenic activity in cancer cachexia and the inhibition of UCPs or the browning of adipose tissue may be beneficial to treat cancer cachexia . A small clinical pilot study comparing cancer patients without weight loss vs. cancer patients with weight loss showed that patients with cancer-associated weight loss had decreased abdominal adipocytes, higher circulating IL-6, increased lipolysis through the overexpression of the ATGL gene, and the browning of adipose tissue through the UCP-activating gene PGC-1a. That study also found that Cidea may be involved in promoting WAT browning by inhibiting UCP-1 repression activity, indicating that the UCP-1 protein was detected in peritumoral white adipocytes in seven out of the eight patients having different types of the tumor but was not detected in ten weight-stable patients . MAC16 tumor-bearing mice showed the overexpression of UCP-1 in BAT, which may be to counter the effect of the hypothermia generated by tumor-derived factors. BAT thermogenesis results in increased energy expenditure, leading to wasting syndrome. The overexpression of UCP-2 and UCP-3 in the skeletal muscle may result in decreased food intake and increased lipid mobilization through increased lipolysis from WAT . A lipid-mobilizing factor was extracted and purified from the urine of cancer cachexia patients who had a weight loss of more than 10%. When repeated i.v. injections of LMF were given to NMRI mice, they showed significant weight loss in gonadal fat mass as well as interscapular BAT. The secretion of leptin from adipocytes was significantly reduced, and mRNA levels of UCP-1, UCP-2, and UCP-3 were significantly increased. The upregulation of UCP-1, UCP-2, and UCP-3 in BAT and UCP-2 in the skeletal muscle and liver suggested that UCPs were involved in utilizing an excess of fat to induce heat production and thereby increased catabolism and energy expenditure in cancer cachexia . Many different interventions have been assessed to inhibit the browning of adipose tissue by inhibiting the overexpression of UCP-1 as well as the factors involved in the phenotype change from WAT to BAT. Luan Y et al. first reported that cachectic mice showed increased expression of p38 MAPK signaling, which activates thermogenesis in adipocytes by activating UCP-1 expression . Another study reported that the p38 MAPK inhibitor SB203580 was able to block the activation of the MAPK pathway by inhibiting pancreatic tumor release exosomes in humans and 3T3-L1 adipocytes. P38a, a member of the p38 MAPK signaling pathway, is known to be involved in activating several proteins in lipid metabolism . p38 MAPK inhibitors VCP979 and SB203580 were able to inhibit p38a and the b subunits of the p38 MAPK pathway, thereby decreasing the overexpression of UCPs and the browning of adipose tissue. These studies have shown the role of UCPs in activating the browning of WAT and increased energy expenditure due to it. The inhibition of UCPs or their upstream pathway may be beneficial to ameliorating the progression of cachexia in cancer . A study conducted by Rohm et al. showed that decreased AMPK activity in the wasting of adipose tissue during cancer cachexia and targeting the WAT AMPK-Cidea interaction may prevent WAT browning in cachectic conditions. That study suggested that AMPK decrease occurs during the late stage of cachexia. It also questioned the stand-alone role of the overexpression of UCP-1 as a driving force of energy expenditure in cachexia. The study concluded that the inactivation of AMPK results in the browning and wasting of adipose tissue, and the stabilization of the AMPK activity in WAT prevents the browning and wasting of WAT . Another study also supported the claims of the previous study and demonstrated that the extracts of Arctium lappa L. were able to lower the expression of UCP-1 by activating AMPK in WAT and BAT . A study evaluating the role of free fatty acid (FFA) receptors FFA1 and FFA4 in cancer cachexia found that UCP-1 was not expressed in the interscapular WAT. Epididymis WAT showed UCP-1 expression in tumor-free mice, while it was downregulated in Lewis lung carcinoma-bearing mice regardless of treatment with GW9508 . The same kind of result was obtained by another study on pancreatic cancer cachexia, which showed a reduction in UCP-1 expression in BAT and WAT with the progression of cachexia. The author concluded that the expression of UCP-1 increases in the early stage of cachexia, which may be due to sympathetic modulation . 9. Conclusions The current review sheds light on the role of UCPs and mitochondrial uncoupling. Very limited studies have been carried out to evaluate the exact role of UCPs in cancer-induced cachexia. UCPs are highly abundant in WAT and BAT and play important roles in non-shivering thermogenesis in the expanse of FFAs. Many studies have shown the upregulation of UCPs in adipose tissue. However, several studies highlighted the fact that even though UCPs were upregulated in WAT and BAT in cancer cachectic conditions, they were not exclusively involved in inducing cachexia. The upregulation of UCPs may be due to other factors involved during cachexia, and UCP activation just exaggerates the cachectic condition. In the context of the skeletal muscle, detailed studies are required to identify the role of UCPs in the context of cancer-associated cachexia. As discussed earlier, the upregulation of UCP-2 and UCP-3 was found to contribute to skeletal muscle loss during cancer cachexia, although some studies indicated that the upregulation of UCPs does not have any direct effect on skeletal muscle loss. More robust preclinical and clinical trials are required to unlock the mystery of UCPs in cancer cachexia. Based on the available studies, we can conclude that UCPs have two important roles. For diseases such as obesity, cardiovascular complications, and neurological complications, UCPs act as protagonists, while in cachexia and cancer, UCPs act as antagonists. The main role of UCPs is to maintain the proton flux across the mitochondrial membrane; nevertheless, UCPs impart many physiological changes in a particular disease condition. Different studies have revealed different responses from different UCPs, and most of the signaling remains complex and controversial and depends upon a vast number of other parameters. Thus far, UCP-1, UCP-2, and UCP-3 have been studied in a very limited way in cancer cachexia, and only their expression has been measured and identified, but no drug or molecule has been developed. The development of drugs acting on UCPs, along with targeting other molecules, could be a potential therapeutic option to halt or cure cachexia in cancer patients. Acknowledgments This manuscript is a part of the Ph.D. thesis of Mit Joshi, to be submitted to Nirma University, Ahmedabad, India, and the authors are thankful to Nirma University for providing the required support for the same. We want to thank and acknowledge Indian Council of Medical Research for providing Senior Research Fellowship to Mit Joshi. Author Contributions M.J. performed the literature review, drafted and edited the review, and contributed to the creation of figures. B.M.P. conceptualized the idea and paper and reviewed and approved the final draft of the paper. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest The authors declare no conflict of interest. Figure 1 Features of cancer cachexia. Irreversible weight loss, anorexia, skeletal muscle loss, and adipose tissue loss are four cardinal features of cancer cachexia. Loss of adipocyte, skeletal muscle, and anorexia leads to irreversible weight loss in cachectic patients. Change in orexigenic signals, and imbalance in adipokine secretion results in anorexia. Side effects of chemotherapeutic drugs result in vomiting and nausea, leading to a decrease in food intake, while depression, a very common symptom among cancer patients, further promotes a decrease in food intake. Chronic inflammation due to the immune system and host-tumor interaction upregulates protein degradation cascade, mainly ubiquitin proteasomal and autophagy pathway, and downregulates protein synthesis pathway, leading to skeletal muscle loss primarily through acting on myocytes and myofibril formation. Inflammation and tumor-derived factors lead to increased lipolysis and decreased lipogenesis. High energy expenditure is initiated due to the activation of brown adipose tissue and phenotypic change from white to beige adipocytes. Complex cellular and molecular pathways lead to the initiation of cachexia in cancer patients. Figure 2 Molecular mechanism of UCP in cancer cachexia. Host and tumor-derived factors such as IL-6, TNF-a, catecholamines, PTHrP, and LMF cause activation of STAT/FOXO, NF-kB, and p38/MAPK, leading to activation of PKA, as well as PPAR-g, PGC-1a, and PRDM16. Activation of these proteins leads to differentiation and phenotypic changes in adipocytes. This protein causes activation of UCPs in white, beige, and brown adipose tissues, causing increased lipolysis and energy expenditure. High energy expenditure causes loss of adipose tissue and skeletal muscle, ultimately leading to cancer cachexia. Activation of STAT/FOXO, NF-kB, and p38/MAPK is also involved in the pathophysiology of anorexia, which further causes activation of UCPs and results in skeletal muscle and adipose tissue wasting and cachexia. The upregulation of UCPs in skeletal muscle, and its role in skeletal muscle wasting in cancer cachexia, are still debatable, and further studies are required to decipher its role. IL-6: interleukin-6, TNF-a: tumor necrosis factor-a, LIF: leukotriene inhibitory factor, PTHrP: parathyroid hormone-related protein, STAT/FOXO: signal transducer and activator of transcription/class O forkhead transcription factors, NF-kB: nuclear factor kB, p38/MAPK: p38 mitogen-activated protein kinases, PKA: protein kinase A, PRDM16: PR domain containing 16, PPAR-g: peroxisome proliferator-activated receptor gamma, PGC-1a: PPARG coactivator 1 alpha. ?--The exact role of UCP activation in skeletal musle during progression of cancer cachexia is still not known. Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
PMC10000252 | Background For family caregivers, who are generally regarded as a vulnerable population, having regular checkups is a desirable health behavior. This study examined family caregivers' habit of having regular checkups prior to becoming involved with professionals who care for patients, and whether they had had recent checkups. We then examined the association between family caregivers' experience with professionals and their participation in checkups after adjusting for the past habit. Methods We conducted a cross sectional survey in Japan between November and December 2020. We recruited family caregivers who were aged 40-74 years and caring for community-dwelling adult patients. The outcome variable was whether family caregivers had undergone any health checkups since April 2019. We assessed family caregivers' experience using the Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS). Results Of the 1091 recruited family caregivers, 629 were included in the analysis. Of these, 358 had previously undergone regular checkups, and 158 had no checkups or selected the option "unknown." Outcome rates in each group were 74.6% and 43.0%, respectively, and 62.0% for all 629 caregivers. Multivariate modified Poisson regression analysis revealed that among the J-IEXPAC CAREGIVERS scores, only the domain score for attention for the caregiver was significantly associated with family caregivers' participation in checkups (adjusted prevalence ratio per 1 SD increase = 1.07; 95% CI 1.01-1.14). Conclusions Among family caregivers' experience with professionals, the factor that focused on caregivers themselves was significantly associated with their participation in checkups. This finding underscores the significance of caregiver-focused care. This study examined the association between family caregivers' experience with professionals and their participation in health checkups after adjusting for multiple possible confounders, including a past habit of having regular checkups. Among family caregivers' experience with professionals, the factor that focused on caregivers themselves was significantly associated with their participation in checkups. Our findings should encourage healthcare and social care professionals to try to improve family caregivers' experience by focusing on the caregivers themselves. caregivers health behavior healthcare quality assurance health services evaluation person-centered care primary health care Over-the-counter Drug Self-Medication Promotion FoundationR2-3A-002 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Nakayama G , Masumoto S , Haruta J , Maeno T . Family caregivers' experience with healthcare and social care professionals and their participation in health checkups: A cross sectional study in Japan. J Gen Fam Med. 2023;24 :110-118. 10.1002/jgf2.599 pmc1 INTRODUCTION The rapidly aging world population and increasing incidence of chronic diseases is leading to a rise in the roles and needs of family caregivers as elderly patients (care recipients) increasingly rely on family members to support their daily activities. 1 Previous studies have reported that family caregivers have more problems with their psychological or physical health than noncaregivers. 2 , 3 Family caregivers are also reported to underutilize needed healthcare services, 4 and to tend to subordinate their own health needs to those of others. 5 Therefore, family caregivers are a population that warrants a strategic public health approach. Indeed, the Centers for Disease Control and Prevention (CDC) has released several calls to action in support of family caregivers. 6 These include encouraging family caregivers to have regular health checkups. 6 Having regular health checkups is a desirable health behavior for family caregivers. 7 , 8 Although the effectiveness of checkups in the general population is controversial, 9 , 10 , 11 checkups have been associated with controlling risk factors, incorporating preventive services, and improving patient-reported outcomes, 12 and are therefore considered particularly appropriate for vulnerable populations, such as those with low self-rated health and poor connection to primary care. 12 Family caregivers represent such a vulnerable group, 2 , 3 , 4 , 5 and having regular checkups is therefore a desirable health behavior. In countries like Japan and South Korea, where the government already recommends regular checkups for the general population, special attention is considered necessary to encourage family caregivers to undergo health checkups. 13 , 14 A recent examination of health checkups among family caregivers found that family caregivers who had more positive experiences with healthcare and social care professionals - in other words, positive interactions between the caregiver and the professionals who care for patients - were more likely to participate in health checkups. 15 This concept of experience has attracted attention as a means of evaluating the quality of professional care from the caregiver's perspective. 16 , 17 The authors suggested 15 that family caregivers with more positive experiences received more emotional support for their own health and well-being from professionals, and as a result may have paid more attention to their own health and tended to participate in checkups; to our knowledge, the study is the first to suggest an association between family caregiver experience with professionals who care for patients and their participation in health checkups. Nevertheless, it has some limitations. First, the study was a secondary analysis of data from scale development, and the sample size was small. Second, there were potential unmeasured confounders. In particular, the study did not consider family caregivers' habit of having regular checkups prior to becoming involved with professionals who care for patients. Because such past habits may have a significant impact on participation in current checkups, we believe that adjusting for a past habit may lead to a more robust examination. In this study, we first examined family caregivers' habit of having regular checkups prior to becoming involved with professionals who care for patients with chronic conditions, and whether they had had recent checkups. We then examined the association between family caregivers' experience with these professionals and their participation in health checkups after adjusting for possible confounders, including a past habit of having regular checkups. 2 METHODS 2.1 Design, setting, participants and procedures We conducted a cross sectional survey, the Caregivers' own Health And their eXperience of care Ibaraki Survey (CaregiversHAXIS), in Ibaraki Prefecture, located northeast of Tokyo, in November and December, 2020. We recruited family caregivers who were caring for community-dwelling adult patients under the supervision of care managers working in three municipalities in Ibaraki (Appendix S1). Under Japan's Long-Term Care Insurance (LTCI) system, care managers support adult patients and their family caregivers by managing and coordinating the roles of other healthcare and social care professionals. 18 The researchers instructed the care managers to recruit family caregivers consecutively, in order of their original appointments with patients and family caregivers. To be eligible, family caregivers were required to be caring for patients who were suffering from "chronic conditions." 19 All data on family caregivers were collected using a self-administered questionnaire. The family caregivers provided informed consent via the questionnaires and directly returned the questionnaires by mail to the office of our university. 2.1.1 Inclusion criteria Study participants were eligible for this study if they were aged 40-74 years and had been using LTCI for >=1 year. The Japanese government places particular emphasis on health checkups for people aged 40-74 years. 20 2.1.2 Exclusion criteria Family caregivers were excluded from the study if they answered >=2 questionnaires per person, because caregivers caring for two or more people were instructed to limit their responses to the care of the most dependent patient; provided care with a frequency of "once or less in several days," 21 because family caregivers who provide less frequent care are reported to have limited contact with professionals 17 ; or had undergone any health checkups since April 2019 but before starting LTCI use, because the time at which family caregivers began engaging with professionals was chosen to represent the time of the first LTCI use. 2.2 Measures 2.2.1 Outcome variable: Participation in health checkups The outcome variable was whether family caregivers had undergone a health checkup since April 2019. Based on the Comprehensive Survey of Living Conditions (CSLC) questionnaire administered by the government, 22 we used the following question to determine if caregivers had undergone a health checkup: "Have you had any health checkups (a health checkup or a thorough medical checkup) since April 2019?" This question excluded dental checkups, examinations to diagnose a suspected disease or follow-up, or screening for cancer only. 22 While the CSLC questionnaire typically asks about participation in health checkups "in the past year," we modified the time period to "since April 2019" to include family caregivers who may not have undergone a health checkup "in the past year" owing to the effects of coronavirus disease 2019. In Japan, the annual health checkup system covers the period from April to March. 2.2.2 Explanatory variable: Family caregivers' experience with healthcare and social care professionals who care for patients The Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS) 23 was used to assess family caregivers' experience. IEXPAC CAREGIVERS focuses on the interaction between family caregivers and professionals who care for patients with chronic conditions. 16 This scale was developed and validated in Spain, based on the Instrument to evaluate the EXperience of PAtients with Chronic diseases (IEXPAC), which was in turn theoretically based on the Chronic Care Model (CCM). 24 Because the CCM places importance on the systematization of primary care, 25 IEXPAC scales were designed to evaluate a range of professionals, rather than any specific one. J-IEXPAC CAREGIVERS evaluates professionals such as primary care physicians, nurses and care managers from the family caregiver's perspective. This scale consists of two dimensions--attention for the patient and attention for the caregiver. The former dimension captures the process by which professionals work with caregivers to provide care for patients and the latter captures the process by which professionals provide care to family caregivers as co-clients. Each item is rated on a five-point Likert scale ranging from 1 (Never) to 5 (Always). A scale score is calculated by simply summing the scores for each of 12 items, with total scores ranging from 12 to 60. A higher total score indicates higher quality of integrated care from the caregiver's perspective. The internal consistency (Cronbach's alpha) determined in the J-IEXPAC CAREGIVERS development study was 0.92. 23 2.2.3 Covariates Based on studies that examined factors that affect participation in disease screening or health promotion behaviors among family caregivers, 14 , 26 , 27 we included the following as possible confounders in the association between family caregivers' experience and their participation in health checkups: age, gender, relationship with care recipient, self-rated health, type of insurance, educational attainment, annual household income, municipality of residence, caregiving time, caregivers' experience as patients (caregivers' PX), social support by relatives or acquaintances and participation behavior in health checkups before starting LTCI use. Caregiving time was determined using a question based on the CSLC questionnaire. 21 Because daily caregiving time strongly reflects patient deficiencies in activities of daily living, 28 we did not include the patients' functional status as a covariate in the present study. Caregivers' PX was measured using the Japanese version of Primary Care Assessment Tool Short Form (JPCAT-SF). 29 We first assessed whether the subject had a usual source of care and, if so, measured PX in primary care with the overall JPCAT-SF score. To determine social support by relatives or acquaintances, we measured emotional support, which has in particular been shown to be associated with preventive health behaviors. 30 , 31 Because the breadth of our questionnaire was limited, we used the following item to determine emotional support based on previous research 32 : "I have relatives or acquaintances who listen to my worries and fears (other than the professionals who care for me and my loved ones)." Participants chose from responses ranging from 1 (Disagree) to 5 (Agree). 2.3 Statistical analysis We reported the characteristics of family caregivers and the distribution of the J-IEXPAC CAREGIVERS score. We also described information about participation in health checkups before and whether they had had recent checkups. A robust (modified) Poisson regression model was used to determine whether the J-IEXPAC CAREGIVERS total score and each domain score were positively associated with participation in health checkups. We analyzed the unadjusted association between J-IEXPAC CAREGIVERS scores and outcome by calculating the crude prevalence ratio in bivariate regression. In the multivariate regression, the variables described in "Covariates" were included as possible confounders. All variables except J-IEXPAC CAREGIVERS score and age were divided into multiple categorical variables. Municipality of residence was categorized into two groups (Appendix S1). Caregivers' PX was categorized into four groups: no usual source of care or unknown, and tertiles of JPCAT-SF total score. Social support by relatives or acquaintances was categorized into three groups: disagree or partly disagree, neither agree nor disagree, and partly agree or agree, based on a previous study. 31 Participation behavior in health checkups before starting LTCI use was categorized into the following three groups by combining the "no participation" and "unknown" options into one category: regular participation, occasional participation, and no participation or unknown. We included each J-IEXPAC CAREGIVERS score separately in the model and interpreted the results without Bonferroni correction. Participants with missing data were excluded from all analyses. Since the use of logistic regression analysis was planned during the study planning stage, the sample size setting and the results of logistic regression analysis are presented as a supplement (Appendix S2). Statistical analyses were conducted using SPSS Statistics version 28 (IBM Corp.). 3 RESULTS 3.1 Participants' characteristics and descriptive analysis of the J-IEXPAC CAREGIVERS score Of the 1091 recruited family caregivers, 887 (81.3%) responded to the questionnaire. Figure 1 shows a flow chart of the study participants, with 629 (57.7% of 1091) ultimately included in the analysis. Table 1 shows the characteristics of the 629 family caregivers. Median age was 62 years, and the majority were women (74.7%). FIGURE 1 Flow chart of participants. J-IEXPAC CAREGIVERS, Japanese version of the Caregivers' Experience Instrument. TABLE 1 Family caregivers' characteristics (N = 629) Characteristic Total (N = 629) Gender, N (%) Men 159 (25.3) Women 470 (74.7) Age (years), median [IQR] 62 [56-68] Relationship with care recipient Spouse 120 Child 375 Child-in-law 111 Parent 7 Sibling 6 Other 10 Self-rated health, N (%) Poor 34 (5.4) Not very good 112 (17.8) Good 368 (58.5) Very good 115 (18.3) Insurance type, N (%) National insurance 329 (52.3) Employee's insurance, employees 158 (25.1) Employee's insurance, dependents 126 (20.0) Other 16 (2.5) Education, N (%) Did not complete high school 20 (3.2) High school 284 (45.2) Career college, junior college, or higher professional school 191 (30.4) College or graduate school 134 (21.3) Annual household income (million JPY), N (%) <2.50 (about USD 24,000) 219 (34.8) 2.50-4.99 246 (39.1) 5.00-7.99 103 (16.4) >=8.00 61 (9.7) Municipality of residence, N (%) One of the three municipalities where recruitment was conducted 541 (86.0) Other 88 (14.0) Social support by relatives or acquaintances a , N (%) Disagree or partly disagree 103 (16.4) Neither agree nor disagree 69 (11.0) Partly agree or agree 457 (72.7) Caregiving time per day, N (%) Almost all day 114 (18.1) Half day 113 (18.0) 2-3 h 110 (17.5) Lend a hand when needed 292 (46.4) Caregivers' PX, N (%) No usual source of care or unknown 244 (38.8) Lower tertile (Tertile 1) b 134 (21.3) Middle tertile (Tertile 2) b 125 (19.9) Higher tertile (Tertile 3) b 126 (20.0) Abbreviations: IQR, interquartile range; PX, patient experience; LTCI, long-term care insurance. a "I have relatives or acquaintances who listen to my worries and fears (other than the professionals who care for me and my loved ones)." b Tertile 1, 2.1 to 33.3; Tertile 2, 33.4 to 47.9; Tertile 3, 48.0 to 100. Table 2 shows the mean and standard deviation (SD) of the J-IEXPAC CAREGIVERS total score and the proportion of family caregivers who responded "always" or "almost always" to each J-IEXPAC CAREGIVERS item. The average J-IEXPAC CAREGIVERS total score was 40.7 (SD 8.3) out of 60 points. TABLE 2 Japanese version of the Caregivers' experience instrument (J-IEXPAC CAREGIVERS) score and the proportion of family caregivers who selected "always" or "almost always" to each J-IEXPAC CAREGIVERS item (N = 629). Mean (SD) Total score 40.7 (8.3) Domain scores Attention for the patient (items 1, 2, 4, 5, 6, 7, and 8) 26.1 (5.0) Attention for the caregiver (items 9, 10, 11, and 12) 12.5 (3.3) Always/almost always responses (%) 1. They respect the lifestyle of the person I care for 72.7 2. They are coordinated to offer us good care 52.9 3. They help me become informed via the Internet 12.2 4. I now know how to look after them better 43.1 5. They ask me about and help me follow the treatment plan of the person in my care 73.0 6. We agree on the most important objectives of their care to control their health problems better 67.9 7. They ensure that he/she takes the medication correctly 47.5 8. They are concerned about the wellbeing of the person in my care 74.1 9. They are concerned about my health and well being 56.4 10. They are concerned about my emotional and physical burden 49.0 11. They inform me about health and social resources that can help me 49.8 12. They encourage me to talk to other caregivers 6.0 Note: J-IEXPAC CAREGIVERS evaluates a range of professionals such as primary care physicians, nurses and care managers, rather than any specific one. The items listed in this table are written as they are in the original English version of IEXPAC CAREGIVERS. The text of each item shows only a portion of the original, and the full text is available online ). IEXPAC(c)2015. Abbreviation: SD, standard deviation. 3.2 Family caregivers' past habit of having regular checkups and participation in recent checkups Table 3 shows the distribution of family caregivers by past habit of having regular checkups, and participation in recent checkups. Sixty-two percent of all 629 caregivers indicated that they had participated in a health checkup since April 2019. Of the 358 family caregivers who had been in the habit of having regular checkups, 91 (25.4%) caregivers had not undertaken a recent checkup. On the other hand, of the 158 family caregivers who had no checkups or selected the option "unknown," 68 (43.0%) had participated in a recent checkup. TABLE 3 Family caregivers' past habit of having regular checkups and participation in recent checkups (N = 629). Participation in recent checkups c No Yes Total Past habit a Regular participation 91 (25.4%) 267 (74.6%) 358 Occasional participation 58 (51.3%) 55 (48.7%) 113 No participation or unknown b 90 (57.0%) 68 (43.0%) 158 Total 239 (38.0%) 390 (62.0%) 629 a Participation behavior in health checkups before starting long-term care insurance use. b Those who had no checkups (n = 140) or selected the option "unknown" (n = 18). c Participation in health checkups since April 2019. 3.3 Associations of J-IEXPAC CAREGIVERS score with family caregiver participation in health checkups Table 4 shows the results of bivariate and multivariate modified Poisson regression analyses of the association of J-IEXPAC CAREGIVERS scores with family caregivers' participation in health checkups. In bivariate (unadjusted) models, the J-IEXPAC CAREGIVERS total score and the domain score for attention for the caregiver were significantly associated with family caregivers' participation in health checkups. After adjusting for possible confounders, only the domain score for attention for the caregiver was positively associated with family caregivers' participation in health checkups (adjusted prevalence ratio per 1 SD increase = 1.07; 95% CI 1.01-1.14). TABLE 4 Associations of the Japanese version of the Caregivers' Experience Instrument (J-IEXPAC CAREGIVERS) scores with family caregiver participation in health checkups (N = 629). Bivariate model a p Value Multivariate model a , b p Value Crude PR (95% CI) c Adjusted PR (95% CI) c J-IEXPAC CAREGIVERS Total score 1.07 (1.01-1.14) 0.026 1.06 (0.99-1.12) 0.079 Domain scores Attention for the patient 1.06 (1.00-1.13) 0.051 1.04 (0.98-1.11) 0.205 Attention for the caregiver 1.08 (1.01-1.15) 0.012 1.07 (1.01-1.14) 0.028 Abbreviations: CI, confidence interval; PR, prevalence ratio. a Each score was included separately in the model. b All three models were adjusted for age, gender, relationship with care recipient, self-rated health, insurance type, education, annual household income, municipality of residence, social support by relatives or acquaintances, caregiving time per day, caregivers' experience as patients (caregivers' PX), and participation behavior in health checkups before initiation of long-term care insurance use. c Per 1 SD (standard deviation) increase. 4 DISCUSSION We first examined family caregivers' habit of having regular checkups prior to becoming involved with professionals who care for patients, and whether they had had recent checkups. We found that 25.4% of family caregivers who had been in the habit did not undertake a recent checkup, whereas 43% of family caregivers who had no checkup habit (including those who selected "unknown") had received a recent checkup. We then examined the association between family caregivers' experience with professionals, as measured by the J-IEXPAC CAREGIVERS score, and their participation in recent checkups after adjusting for a past habit of having regular checkups. Results showed a significant association only for the domain score attention for the caregiver among the J-IEXPAC CAREGIVERS scores. Our findings reinforce the importance of enhancing care that focuses on family caregivers within the context of their having checkups as their own care. The results of past habits and recent health checkups in family caregivers can be explained by the transtheoretical model of behavior change (TTM), which describes the following stages of change: precontemplation, contemplation, preparation, action, maintenance and termination. 33 We found that 25.4% of family caregivers who had been in the habit of having regular checkups did not have recent checkups. This finding is similar to that of previous research conducted in the U.S., which showed that while middle-aged and older family caregivers engaged in 86% of recommended preventive health practices, including blood pressure and cholesterol screenings, in the past, they currently conduct only 63% of these practices. 34 According to TTM, even for people who have reached the stage of maintaining their desired behavior, the temptation to step back is very strong. 35 Triggers for this temptation include negative affect or emotional distress, and social situations. Our present and previous findings 34 suggest that caregiving responsibilities may also be a trigger. On the other hand, we found that 43% of family caregivers who reported not having a checkup habit (including those who selected "unknown") had engaged in recent checkups. These family caregivers may have previously been at a stage prior to "action," but their caregiving responsibilities may have led them to become concerned about their health and consequently to take action (i.e., having checkups). Family caregivers who participated in a qualitative survey perceived their self-care to be negatively affected by caregiving and, in response to a question about the things they considered to be important in self-care, reported that having regular checkups was one way for them to maintain their health. 36 Thus, caregiving responsibilities may have conflicting effects on the family caregivers' decision to have checkups. After controlling for variables related to caregiving responsibilities and a previous habit of having regular checkups, the only score significantly associated with participation in health checkups was attention for the caregiver. This differs from the results of a previous preliminary analysis, in which all scores were significantly associated with participation in health checkups. 15 The significance of the domain score for attention for the caregiver was common in both studies, which is theoretically understandable because the main construct of this domain is the family caregiver's perception of whether the caregiver has professional care support for his or her own health and well-being, and to obtain information to help acquire such support. Interpersonal relationships in facilitating and preserving well-being prevents and buffers stress; increases connectedness, control and self-esteem; and consequently promotes health behaviors. 37 On the other hand, the domain score for attention for the patient was significant in the previous study but showed no significance in the present study. In the previous study, it was noted that this domain score may be significantly associated with participation in health checkups because the two domain scores for attention for the patient and attention for the caregiver showed high correlation. In the present study, there was a gap in caregivers' recognition of these two compared to the previous study (Spearman's rank correlation coefficient for both domains: r = 0.698 in the present study, r = 0.791 in the previous study), which may have led to the lack of a significant association in the domain score for attention for the patient. Furthermore, the J-IEXPAC CAREGIVERS total score did not show significance in this study, probably because the domain score for attention for the patient accounts for a larger proportion of the total score (Table 2). Given that the previous study was conducted using a convenience sample of limited size, versus the relatively large consecutive sample in the present study, our present results may be more reflective of the population. The strength of the current study is that, compared with the previous study, 15 its more robust comparison shows that the domain score for attention for the caregiver is associated with participation in checkups. This result in turn suggests that caregiver-focused care may have a positive impact on having checkups, even though caregiving responsibilities may have conflicting effects on family caregivers' decision to have checkups. Our findings should encourage healthcare and social care professionals to try to improve family caregivers' experience by referring to the items that comprise the attention for the caregiver domain of J-IEXPAC CAREGIVERS, in the context of caregivers being more aware of care for their own health. Our study also has several potential limitations. First, the results of past habits and recent health checkups in family caregivers were obtained from descriptive statistics, and no comparison with the control group was made. Second, we did not measure social support by relatives or acquaintances using validated measures of psychometric properties. Third, we did not include basic information on the patient (care recipient) in this article, out of respect for the ethical challenge we faced when attempting to obtain direct patient consent at collection. However, as noted in the Methods section, we believe that we were able to adjust confounders appropriately using caregiving time, which reflects patient deficit in activities of daily living. Fourth, the study design was cross sectional, and thus a causal relationship could not be definitively established. However, because we collected time-sensitive data on the timing of family caregivers' engagement with professionals and the occurrence of outcomes after this engagement, we believe that reverse causality is unlikely. 5 CONCLUSION We found that one-quarter of family caregivers who had been in the habit of having regular checkups had not undertaken a recent checkup, whereas approximately 40% of family caregivers who did not have a checkup habit had received a recent checkup. Further analysis revealed that, among family caregivers' experience with professionals, the factor that focused on family caregivers themselves was significantly associated with their participation in checkups. Our findings reinforce the significance of family caregivers' experience, especially in terms of the receipt of care by caregivers themselves, in the context of having checkups as a component of their own care. ETHICS APPROVAL The study was approved by the Ethics Committee of the Faculty of Medicine, University of Tsukuba (approval no. 1518-2). This committee grants approval to studies based on the provisions of the Declaration of Helsinki and Japanese ethical guidelines (Ethical Guidelines for Medical and Health Research Involving Human Subjects). PATIENT CONSENT STATEMENT All participants were volunteers and checked the box on the questionnaire indicating their intention to participate. CLINICAL TRIAL REGISTRATION None. CONFLICT OF INTEREST The authors have stated explicitly that there are no conflicts of interest in connection with this article. Supporting information Appendix S1-S2 Click here for additional data file. ACKNOWLEDGMENTS This study was supported by a grant from OTC Self-Medication Promotion Foundation, Japan (grant no. R2-3A-002). The authors thank the care managers for their cooperation in the survey. We also thank DMC Corp. ) for editing a draft of this manuscript, and Prof Masahiko Gosho for advice on statistical interpretation. |
PMC10000254 | Energy security concerns require novel greener and more sustainable processes, and Paris Agreement goals have put in motion several measures aligned with the 2050 roadmap strategies and net zero emission goals. Renewable energies are a promising alternative to existing infrastructures, with solar energy one of the most appealing due to its use of the overabundant natural source of energy. Photocatalysis as a simple heterogeneous surface catalytic reaction is well placed to enter the realm of scaling up processes for wide scale implementation. Inspired by natural photosynthesis, artificial water splitting's beauty lies in its simplicity, requiring only light, a catalyst, and water. The bottlenecks to producing a high volume of hydrogen are several: Reactors with efficient photonic/mass/heat profiles, multifunctional efficient solar-driven catalysts, and proliferation of pilot devices. Three case studies, developed in Japan, Spain, and France are showcased to emphasize efforts on a pilot and large-scale examples. In order for solar-assisted photocatalytic H2 to mature as a solution, the aforementioned bottlenecks must be overcome for the field to advance its technology readiness level, assess the capital expenditure, and enter the market. The 2050 roadmap strategies and net zero emission goals are made possible through the adoption of novel greener and more sustainable processes. In this regard, exploiting solar irradiation (a plentiful energy source) is advantageous for developing green hydrogen technologies. Photocatalytic devices are suited for large-scale plants proliferation. Three case studies from France, Spain, and Japan are presented. hydrogen net zero emissions photocatalysis roadmap technological development source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 M. Isaacs , J. Garcia-Navarro , W.-J. Ong , P. Jimenez-Calvo , Is Photocatalysis the Next Technology to Produce Green Hydrogen to Enable the Net Zero Emissions Goal?. Global Challenges 2023, 7 , 2200165. 10.1002/gch2.202200165 pmc1 Introduction Today, humankind is confronted by a series of global challenges: energy/environmental crises, population growth, pandemics, and geopolitical wars, that simultaneously promote the depletion of natural resources and accelerate the contamination of sources of life: water, air, and soil. Among these challenges, energy production, and demand deserve special attention by the research and development communities who urgently need to devise tangible solutions. Notably, the continuous conversion of fossil fuels, such as oil, gas, and coal continue to contribute to greenhouse gases emissions, such as carbon dioxide (CO2). Ideally, certain criteria for selecting the future energy sources should be observed, namely, these sources should be abundant, easy to recycle or regenerate at the large scale, and their conversion should be CO2-free. The world's total net CO2 emissions, from 1850 to 2019, were 2400 +- 240 Gt(CO2). Between 2010 and 2019 alone, roughly 17% of the total cumulative net CO2 emissions (410 +- 30 GtCO2) were released, supporting Hubbert's predictions from 1970. The concentration of CO2 in the atmosphere has been directly measured by the Mauna Loa Observatory, exhibiting 417 ppm Figure 1 . Such CO2 increases result in damning and imminent consequences to the natural world. For example, increases to the surface temperature of the Earth consequently impact the average rate of sea levels (e.g., 20 cm rise between 1901 and 2018), desert dryness, melting of glaciers and ice caps, heat content and acidification of the ocean, and other negative effects to various ecosystems. Figure 1 a) Measurements of atmospheric CO2 since 1958 from the Mauna Loa Observatory in Hawaii (black) and from the South Pole (red) show a steady annual increase in atmospheric CO2 concentration. Reproduced with permission. Copyright 2022, Scripps CO2 Program. b) Illustrative scheme to represent the technological transfer from laboratory setups, pilot scale devices, and large-plants. For these reasons, an assessment of existing processes must be carried out to replace them with more efficient and sustainable technologies. For that, a shift from fossil fuels to clean energy has been suggested by the roadmap 2050 (the European Commission (EU)) and Net Zero by 2050 (the EU Green Deal and International Energy Agency). At the present time, fossil fuels still supply 80% of the world's energy. In this context, the use of solar energy is an appealing alternative due to the primary energy source being an effectively unlimited supply of great power. The diversity of emitted photons with different energies that can be selectively captured and thus used for chemical conversion to obtain solar clean fuels makes this a unique source. Nevertheless, the capture of solar photons is a challenge due to the day-night cycle, seasonal change, cloud presence, and geographical local distribution. Among several solar-driven fuels currently under investigation, hydrogen is primarily unlocking the potential of renewables as an energy source, and moving carbon neutrality toward a reality rather than a myth. The attractiveness of H2, as an energy vector, lies in three arguments: a) Its high energy content per unit mass (142 kJ mol-1), twofold to threefold increase compared with classical fossil fuels, such as gasoline, methane, propane, and natural gas, b) versatile energy storage medium because it can be used in electric only or combined heat and power fuel cells in stationary applications, internal combustion engines, and fuel cell vehicles, and c) despite its low self-discharge rate, regenerative hydrogen fuel cells may be cheaper than batteries in an optimized energy arbitrage system. H2 integration into the economic model became a serious consideration following the signing of the Paris agreement by the members of United Nations (UN). One of the goals of this agreement is to decarbonize heavy industry and, for that, reinviting or shifting existing technologies for optimized, greener, and more sustainable processes is a must. Thus, the European Commission, the World Economic Forum, the UN, Mission Innovation, and established industries are implementing new strategies to support net zero emissions and update their portfolio of technologies. With this integration scenario, emerging H2 technologies are achieving historical technology readiness levels (TRL), ranging from laboratory setups into pilot devices and large-plants . However, storage, transport, and safety hindrances must be addressed and refined to enable fully widespread integration into the socio-economical context. H2 safety is undoubtedly a topic to be addressed for a broader implementation and social acceptance. Briefly, the ignition energy of H2 mixed with air (0.017 mJ) is lower than natural gas (0.24-0.31 mJ). As natural gas is already handle in a large scale making a proof-of-concept. Thus, the ignition energy difference points out that theoretically H2 would cause lower flame propagation from the ignition point, thus is safer. Therefore, an ignition endanger will be consider when a source is close (e.g., spark or over heated contact). Experiments have shown that H2 does not ignite in cases where it was expected under specific circumstances, namely in presence of friction or energized devices. Still, more maturity in ignition tests is needed to mitigate and minimize inherent risks (essentially ignition), as reached for natural gas. 2 Hydrogen Production Context Worldwide political and scientific consensus have defined a color nomenclature for H2 in function of its source of production. There are eight different colors but for this article we limit the introduction of the three extreme cases, from the most and least contaminant and neutral sources. Please refer to Ajanovic et al. for details. Grey H2 is made with fossil-fuel-based technology, blue H2 is climate-neutral and made with carbon capture and storage technology, and green H2 is made with renewable energy (using renewables). To date, H2 is produced by mostly fossil fuels (98%) emitting nearly 900 million metric tons (Mt) of CO2 per year. By 2020 H2 production reached 90 Mt. It is forecasted, however, that H2 production may surpass 200 Mt in 2030. Steam methane reforming (76%) is the leading H2 production technology in the market, followed by coal gasification (22%), two energy-intensive and highly polluting methods. Electrolysis, a clean but relatively adolescent technology is already in the loop of existing technological processes contributing to 2% of total production, evidencing the need to decentralize H2 production to facilitate the integration with downstream processes to foster a sustainable energy transition. The output stream of electrolyzers is a mixture of H2 and O2. Thus, a common practice consists in using gas separation processes, (also in fuel cells and steam methane reforming with the equivalent or other by-product gases) in the end production point with possible recirculation for increasing the efficiency itself and obtained a higher H2 purity. The high-quality H2 with the desired low impurity levels is achievable with either adsorption and diffusion purification processes. The commercial technology widely used for adsorption-based H2 purification is Pressure Swing Adsorption (PSA), where porous solid adsorbents (e.g., zeolites and activated carbons) preferentially adsorb particular components from a gas stream in a pressurized vessel, later to be released after depressurization, that is, pressure cycles. Besides PSA, there are other methods based on temperature (TSA) and/or vacuum (VSA) but purities and cost differ. The amount of H2 made from renewable sources, like water or biomass, is a small part of the total amount produced. Fortunately, there are several methods to obtained H2 and O2 via water splitting (WS), namely electrolysis, electrocatalysis, photocatalysis (PC), photoelectrocatalysis, photovoltaic-electrochemical, solar thermochemical cycles, photothermal catalytic, or photobiological processes. WS is an uphill reaction that requires a significant Gibbs free energy, that is, 237 kJ mol-1. Interestingly, WS requires a very similar amount of energy as natural photosynthesis, with plants needing 1.24 eV (energy required per electron driven through the photosynthetic system) to make glucose, whereas to split water artificially requires 1.23 eV per electron. This thermodynamic requirement of PC H2 production is defined primarily by the water oxidation (oxygen evolution reaction) and then the proton reduction (hydrogen evolution reaction, HER) half-reactions requiring 1.23 and 0 V versus normal hydrogen electrode (pH = 0), respectively. On top of H2 production via WS, PC is an appealing approach for other energy applications, such as CO2 reduction and nitrogen fixation. As heterogeneous catalysis type, PC is particularly simple, requiring only light to activate the solid semiconductor (SC) and transform either a liquid or gas reactant. Unlike, typical electrolyzer connected with a photovoltaic panel, PC simplifies in its unassisted electricity possibility, potentially lowering costs in an operating expenses (OPEX) viewpoint. 3 Photocatalytic Water Splitting Principle PC WS is a heterogeneous surface catalytic reaction and possesses an attractive simplicity, requiring only light, a catalyst, and water to function. For that reason, PC WS is an appealing prospect, and considered one of the "holy grail" reactions in physical chemistry because can directly produce H2 from water. Should the technical barriers be removed whilst maintaining even a moderate capital expenditure (CAPEX), then one can presume it to challenge competitor methods, perhaps eventually reaching an even more attractive cost. Typically, PC WS starts when a SC is irradiated with a photon with equal or higher energy than its band gap. This generates an exciton: excited electron (e-) and a positive hole (h+). These two charge carriers dissociate and migrate to the surface of the catalyst. Some e-/h+ partners face undesirable recombination on the surface or in the bulk, but the e-/h+ pairs reaching the surface may undertake one of the two WS half-reactions. Figure 2 a) Photocatalyst scheme of activation, generation, and reactional water splitting steps. b) Summary of general photocatalytic steps. Successful h+ moieties avoiding recombination can oxidize water to create O2 and H+, while on the other hand, available can reduce the H+ to obtain H2. Therefore, the HER consumes 2 molecule of H2 formed. The four steps of the process (activation, exciton formation, recombination, redox) all involve different time scales, which are well-described by Takanabe et al. Figure 2b summarizes PC WS sequential steps: a) Activation of the catalyst (critical), b) generation of the charge carriers, and c) redox reactions in the interface between the catalyst and the substrate. Prior to catalyst activation there are two pre-reaction steps, first the reactant molecules must diffuse to the liquid-gas/solid interface to be adsorbed onto the catalyst surface. Once on the surface, they then wait to encounter a photo-generated charge carrier and react. Furthermore, after the catalyst's activation, two analogous post-reaction steps then happen. They initially desorb from the catalyst surface and then diffuse back into the reaction media. The critical step (activation of the catalyst) defines the overall efficacy of the material, which occurs mostly in the interior of the catalyst, but some sub-steps may proceed at its surface. Many leading scientists are currently improving the reaction medium/catalyst interface contact with sophisticated advanced material strategies (Z-scheme, Schottky junctions, and co-polymerization, among others) to tune key properties and increase efficiencies. 4 Photocatalytic Technological Developments This section will showcase three photocatalytic systems develop in Asia and Europe. One recently automated laboratory scale reactor, and two pilot devices: A panel photocatalytic array and a compound parabolic collector (CPC). The reasoning is to highlight the international efforts toward improving laboratory photocatalytic systems and the transition into pilot and large-scale processes. The first step toward large-plants, however, is the development and refinement of effective PC devices capable of promising performance on the pilot scale. Considerations of the complexities of benchmarking and effective engineering challenges in developing lab-scale PC materials was addressed in our recent work designing and constructing a compact automated stainless steel reactor, of 40 cm3 of volume. H2 photoproduction and quantum yields exhibited twofold increases when compared to literature equivalent materials. This result emphasizes that reactor geometry and configuration setup play a key role in the performance of PC materials and reveals insights into ideal (minimal losses) heat/mass/photonic profiles. An unprecedented 100 m2 arrayed panel system led by Professor Domen, comprising 1600 units has been recently launched at Kakioka Research Facility at the University of Tokyo. This system design has achieved 0.76% solar-to-hydrogen (STH) conversion, similar to ideal lab scale efficiency, 1% STH. The configuration attractiveness relies in being simple, cheaper, and more amenable to scale-up compared with solar cells and/or electrolysis systems. Each panel plate was sprayed with a modified aluminum-doped strontium titanate photocatalyst layer, one of the most efficient photocatalysts to date. The highlight of this panel array is its H2 recovery after several months of continuous operationality, starting with a moist gas product mixture, and H2 capture with a polyimide membrane. Another pilot device for solar H2 generation and removal of wastewater pollutants was tested at Plataforma Solar de Almeria. This setup consists of a CPC, which is a reactor type enabling highly efficient solar photon collection. Two materials were tested, Pt/(TiO2-N) and Pt/(CdS-ZnS), with the former outperforming the latter in combination with two sacrificial electron donors: formic acid and glycerol. This system evidences other proof-of-concept of H2 production, though this time using municipal wastewaters, enabling simultaneous waste water depollution and energy vector generation. Though several photocatalytic WS prototypes are available, their efficiency is still low (<1%). From a photochemical process perspective, reactor design and process optimization are needed to make this technology viable and feasible on a relevant scale. Furthermore, from a materials science perspective, higher-performing photocatalysts with better stability and H2 production efficiency (5-10% STH) are needed for economic viability. Public and private partnerships are proliferating internationally to tackle these bottlenecks; The Green Deal (European Union) in particular is investing a significant amount into finding tangible renewable solutions. 5 Conclusions and Outlook By maturing solar-assisted photocatalytic H2 technologies on a pilot scale, like in the three case studies, the proof-of-concept stage can be bypassed and thus enable the new chapter of TRL acceleration. The innovation of advanced H2 pilot devices in the next half-decade will be key to unlocking new engineering advances for large-scale that may foster both the commercialization of H2 from solar-fueled photocatalysis across the global market and the circular economy (while decarbonizing with clean energy). For solar scale up reactor design and dimensional technological transfer analysis, we propose a (non-exhaustive) list of parameters extracted from the selected case studies to implement in higher TRL projects, essentially in four axes: operational, photonic, mass, and heat transfer profiles. We suggest such considerations with the intention that WS PC pilot devices proliferate and unlock further technological barriers. Operational considerations include quantification of H2 (data acquisition) within an integrated on-line analytical equipment (gas chromatography) to reduce operational costs in human resources--which is essential for scaling up to TRL >=3 (pilot prototypes). Reactor components should have resistance to pH, corrosion, and exposed environmental conditions. Furthermore, components must be easy to handle and accessible (with a modular assembly design providing an optimal solution to this point), and finally low-cost (low CAPEX and OPEX). Photonic considerations for catalyst activation focus on efficient photon capture and distribution, with suitable geometry to maximize collected light, suitable light absorbing materials, and maximizing use of the solar spectrum. Mass transfer considerations facilitate adsorption-desorption interactions, for example the reactor must guarantee minimal pressure from the gas flow, ensure suspended particle homogeneity in the contained volume, and avoid creation of pronounce vortexes of sufficient agitation to disrupt processes. Heat transfer considerations include the use of recirculating chillers directly in the path of the light source or inside the reactor (but not in contact with the particle dissolution) to guarantee a constant temperature, ideally of 20 degC, to avoid thermal catalysis contributions. Ultimately, for large-scale setups, the inclusion of wastewater and or organic pollutants as for substrate source and electron or proton donors or so-called sacrificial agents, respectively, should not be negligible while planning of building the plant. Contrarily, optimal processes envisage the simultaneous reuse of one of source (wastewater)--resulting in the production of decontaminated (of organic pollutants) water and concomitant generation of energy solar carriers. Conflict of Interest The authors declare no conflict of interest. Acknowledgements Prof. Dr. Markus Antonietti is acknowledged for his support. The Max Planck Society supported this research financially. M. A. Juan Rodriguez is acknowledged for his graphical design contribution. The acknowledgements section was added and corrections made to references 19, 41 and 43 after initial online publication, on March 10, 2023. Open Access funding enabled and organized by Projekt DEAL. |
PMC10000258 | Objective Syncope is a common clinical condition in the elderly, associated with significant morbidity and risk of recurrence. Recurrent syncope causing a repeated reduction in the cerebral blood flow can predispose to progressive neurodegeneration, a decline in overall health and functionality. Hence, this study was conducted to study the common causes of recurrent syncope and its association with various geriatric syndromes. Methodology This case-control study recruited 50 cases of recurrent syncope and 50 controls, aged 75 years and older. A detailed history and sequential evaluation for aetiologies of recurrent syncope were done. Cognition, frailty, activities of daily living, depression, and nutrition were assessed using various scales. Results Most (80%, 80/100) of the participants were males and the mean age was 80.04 +- 4.3 years. In the syncope group, 42% (21/50) of patients had arrhythmia, and 30% (15/30) had valvular heart disease. Recurrent syncope was significantly associated with lower scores on Montreal cognitive assessment scale (OR: 6.47 P < 0.001), four or more comorbidities (OR: 6.29 P < 0.001), and hearing impairment (OR: 6.21 P < 0.004) on multivariate logistic regression analysis. Conclusion Recurrent syncope is significantly associated with cognitive impairment, the presence of four or more comorbidities, and hearing impairment. Conduction abnormality was the most common etiology of recurrent cardiovascular syncope. Structured evaluation and appropriate management of recurrent syncope might reduce the decline in physical, cognitive, and psychological reserve. A follow-up longitudinal study is needed to establish this. Cardiovascular syncope is the most common cause of recurrent syncope in the elderly and is associated significantly with cognitive impairment, the presence of four or more comorbidities and hearing impairment. Conduction abnormality is the most common etiology for recurrent cardiovascular syncope. Structured evaluation of syncope to identify etiology and appropriate management of cardiovascular syncope might reduce the decline in physical, cognitive, and psychological reserve among older adults. cognitive impairment geriatric syndrome hearing impairment heart disease multimorbidity syncope source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Bandhu K , Rao A , Nehra A , Dwivedi SN , Chakrawarty A , Dey AB . Recurrent syncope in long survivors and its association with geriatric syndromes. Aging Med. 2023;6 :49-55. doi:10.1002/agm2.12240 pmc1 INTRODUCTION Syncope is defined as a transient loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. 1 Syncope is a common symptom in the elderly; the incidence increases rapidly with advancing age. The annual incidence of syncope is 5.7 episodes per 1000 individuals between 60 and 69 years and 11.1 episodes per 1000 individuals between 70 and 79 years, and after 80 years it rises to 19.5 per 1000 individuals. 2 The recurrence is more frequent with increasing age, cardiac comorbidities, and the use of multiple medications. 3 Most syncope in the elderly is due to cardiovascular etiology, most of which can be treated and further syncope prevented. 4 The underlying mechanism for syncope is a sudden temporary reduction in cerebral perfusion mainly to the reticular activating system, which maintains consciousness. 1 Sudden cessation of blood for 6 to 8 seconds or reduction of systolic blood pressure to 60 mmHg or less leads to transient loss of consciousness. Age-related changes in heart rate variability, cerebral autoregulation, blood pressure, the sensitivity of baroreflex arc, intravascular volume regulation, multiple coexisting comorbidities, and concomitant medication use impair the adaptive responses and predispose the elderly to develop recurrent syncope. 5 Cardiovascular syncope is associated with serious consequences in the elderly, but meanwhile there are therapeutic options available. 4 Syncope is seen commonly in patients with cognitive impairment. Vascular risk factors that lead to micro and macrovascular dysregulation and age-related changes in cerebral autoregulation, genetic susceptibility, and environmental factors play an important role in the reciprocal interaction between cerebral hypo-perfusion and amyloid beta accumulation and neurodegeneration leading to cognitive impairment. Indeed, syncope may be the presenting feature of cognitive impairment. Neurocardiovascular instability (NCVI) or "age-related hypotensive syndromes" are the main cause of syncope in the setting of cognitive impairment. It remains unclear whether syncope is due to a neurodegenerative process or syncope triggers an irreversible cascade, resulting in neurodegeneration and cognitive impairment. 3 , 6 Advancing age and comorbidities increase the risk of syncope and fall and the likelihood of being frail. The homeostenosis of various organ systems in frail elderly inhibits their response to an acute stressor like syncope and predisposes them to fall and functional decline. 3 Recurrent syncope leads to fear of fall and depression and affects the quality of life (QoL). 7 , 8 Considering the above facts, the objective of our study was to evaluate the cause of recurrent syncope in patients aged 75 years or older and assess the association between recurrent syncope and geriatric syndromes and compare the same with the sex-matched controls without recurrent syncope. 2 METHODOLOGY Recurrent syncope was defined as a discharge diagnosis of syncope (ICD-10 R55.9) from either an admission or visit to an emergency department (hospital contact), at any time from the first diagnosis of syncope, i.e., more than one episode of syncope was considered as recurrent syncope. In this cross-sectional comparative study, 50 cases with recurrent syncope were recruited from the geriatric medicine ward and outpatient department of tertiary care hospital in India from March 2015 to October 2017. The Institutional Ethics Committee approved the study (IESC/T-14/21.01.2015), and the study was conducted according to ethical guidelines established by the Declaration of Helsinki and Good Clinical Practice Guidelines. An equal number of individuals without syncope, sex-matched were recruited as controls. The sample size was chosen arbitrarily. Inclusion criteria for the syncope group were individuals aged 75 years or more with recurrent syncope. Inclusion criteria for the control group were individuals with no history of syncope visiting geriatric medicine OPD/ward for management of other medical illnesses. Exclusion criteria for both the groups were subjects not capable of undergoing detailed assessment and those who were previously diagnosed with cognitive impairment. After obtaining the consent for participation in the study, the participants were subjected to a detailed investigation protocol, which included a historical review of current health and coexisting comorbidities like diabetes, hypertension, chronic obstructive pulmonary disease, arthritis, self-reported visual, hearing loss, urinary incontinence, stroke, coronary artery disease, psychiatric illness like depression and anxiety, cancer, and any other significant health issues. Further, the syncope group was evaluated sequentially for the etiology of syncope in the following order: Orthostatic hypotension (when there is a reduction of >=20 mmHg in SBP or >=10 mmHg in DBP within 3 min of standing from a lying down position 9 ) measurement and 12 lead ECG. Echocardiography. Holter monitoring. Carotid sinus massage. Head-up tilt testing comprises two phases: (a) the supine pretilt phase; and (b) the passive head-up tilt. The supine pre-tilt phase lasted at least 5 min when no venous cannulation is performed and at least 20 min when venous blood sampling was done; the tilt angle of 70deg for the duration of 40 min. The test was considered positive when patients experienced syncope or at least near syncope with objective modifications in heart rate (bradycardia) and/or blood pressure (hypotension) measurement. During the sequential evaluation, when the etiology of syncope was found, the next evaluation process was not done. Though the sequential investigations approach was followed in this study, some of the patients had been investigated previously with two or more investigations and those reports were also considered in this study. The geriatric syndromes considered in the study were: Cognitive impairment, depression, frailty, malnutrition, multimorbidity, polypharmacy, urinary incontinence, loss of functionality, fall and fear of fall, vision and hearing impairment. Hindi Mental State Examination (HMSE) 10 & Montreal Cognitive Assessment (MOCA) 11 were done to screen for cognitive impairment and the scores were adjusted according to the literacy levels. For diagnosis of cognitive dysfunction, Montreal Cognitive Assessment (MOCA) was used with a score of 26 or more as normal. To better adjust the MOCA for lesser educated individuals, two points were added to the total MOCA score for those with 4 to 9 years of education and one point for 10 to 12 years of education. 12 MOCA <26 or equivalent was suggestive of cognitive dysfunction. Depression was assessed using the Geriatric Depression Scale Short form (GDS 15 points) 13 ; those with a score of 5 or more were considered positive for depression. Frailty was diagnosed by calculation of frailty index (>=0.25) using 36 deficit model Rockwood criteria. 14 Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF) and were classified as malnourished (0-7), at risk of malnutrition (8-11), and normal (12-14) based on the total score. 15 Assessment of functionality concerning instrumental and basic activities of daily living was done in both the groups using Lawton's scale 16 and Barthel's index, 17 respectively. Subjects with a score of 8/8 and 20/20 on Lawton's scale and Barthel's index, respectively, were considered functionally independent. Fall assessment was done by asking a single question "Have you experienced a fall in the last year?" and any history of fear of fall was also asked. 2.1 Statistical analysis Data were managed in an MS-Excel database and analyzed using STATA 14 software. 18 The correlation of syncope and demographic characters was done. Descriptive analysis was done for all variables and frequency (percentage) for qualitative and mean +- SD or median (quartiles, q1 & q3) were calculated for quantitative variables. The categorical variables were analyzed for association using the Chi-square test. p value < 0.05 was considered significant. To measure the strength of association, univariate logistic regression analysis was done with syncope as dependent variable and was expressed as odds ratio with 95% confidence interval. The covariates that were significantly associated were further analyzed with multivariate logistic regression. 3 RESULTS In this cross-sectional study, with a sample size of 100, 50 individuals with recurrent cardiovascular syncope patients and 50 sex-matched controls were studied. The mean age of the patient enrolled was 80.4 (+-4.30) years in both syncope case and non-syncope control groups of which 80% were male. Type 2 diabetes and hypertension were the two most common comorbidities in both groups. The frequency of coronary artery disease was significantly higher in the recurrent syncope group. All the patients in the syncope group had multimorbidity (two or more comorbidities). Recurrent syncope was significantly associated with four or more comorbidities (76% vs. 40% p < 0.001). The baseline characteristics and comorbidities of the study population are depicted below in Table 1. TABLE 1 Baseline characteristics and comorbidities in the syncope and non-syncope group. Characteristics Syncope (n = 50) Non-syncope (n = 50) P Value Age (mean +- SD) 80.04 +- 4.3 80.04 +- 4.3 1.000** Males 40 (80%) 40 (80%) 1.000 Females 10 (20%) 10 (20%) Literacy 41 (82%) 43 (86%) 0.707 Average BMI (kg/m2) 22.39 22.74 Smoking 26 (52%) 20 (40%) 0.229 Alcohol 18 (36%) 12 (24%) 0.19 Hypertension 34 (68%) 36 (72%) 0.663 Diabetes 22 (44%) 13 (26%) 0.059 Joint pain 28 (56%) 33 (66%) 0.400 Dizziness 48 (96%) 11 (22%) <0.001 Vertigo 3 (6%) 9 (18%) 0.121* Anemia 20 (40%) 17 (34%) 0.534 Hypothyroidism 2 (4%) 4 (8%) 0.059* BPH 17 (34%) 20 (40%) 0.534 Constipation 19 (38%) 22 (44%) 0.542 COPD 10 (20%) 13 (26%) 0.476 CKD 6 (12%) 3 (6%) 0.295 CAD 25 (50%) 14 (28%) 0.024 Cancer 4 (8%) 1 (2%) 0.362* Comorbidities <=1 0 (0%) 4 (8%) 0.117* >=2 50 (100%) 46 (92%) 0.117* >=4 38 (76%) 20 (40%) <0.001 Note: P Value calculated using Chi-square, *Fischer exact test, **unpaired T-test. Bold indicates significantly different in syncope and non syncope group. Abbreviations: BPH, Benign prostatic hyperplasia; CAD, Coronary artery disease; CKD, Chronic kidney disease; COPD, Chronic obstructive pulmonary disease. When the subjects were evaluated according to the sequential protocol for evaluating the etiology of syncope, the most common cause of recurrent syncope was cardiovascular syncope, among which arrhythmia was the most common cause as seen in 42% of the subjects. Sick sinus syndrome was seen in 6% of the subjects with syncope and sinus bradycardia was seen in 2% of the subjects. Valvular heart disease was the second most common etiology of cardiovascular syncope in the elderly accounting for 30% of the cases. Aortic stenosis was the most common valvular disease and accounted for 66.66% of the valvular heart disease causing syncope. DCMP and OH were seen among 10% and 4% of syncope subjects, respectively. Of the syncope patients, 14% (7/50) were found to have other multiple causes of syncope. Cases with multifactorial etiology include AF and a combination of others mentioned in Table 2. All 50 patients underwent 12 lead ECG and blood pressure assessment for orthostatic hypotension, 26 patients underwent echocardiography, 6 patients underwent Holter testing, and 1 patient underwent carotid sinus massage and head up tilt test. TABLE 2 Etiology of recurrent syncope Etiology Number of syncope patients (n = 50) (%) OH 2 (4%) Arrhythmia 21 (42%) a. CHB & 2nd-degree block 17 b. Sinus bradycardia 1 c. Sick sinus syndrome 3 Valvular heart disease 15 (30%) a. Aortic stenosis 10 b. Other valvular disease 5 DCMP 5 (10%) Multifactorial 7 (14%) Note: Bold indicates the 2 most common causes of recurrent cardiovascular syncope. Cognitive assessment using MOCA and HMSE showed significant impairment in the recurrent syncope group as compared to non-syncope subjects with a p value of 0.001 and 0.002, respectively. Similarly, frailty and hearing impairment were also significantly associated with recurrent syncope, with a p value of 0.017 and 0.019, respectively. About 34% of syncope subjects were either malnourished or at risk of malnutrition as assessed using the Mini Nutritional Assessment short form scale for nutrition. Polypharmacy was seen in more than two-thirds of the study population (Table 3). TABLE 3 Comparison of various geriatric syndrome assessments between syncope and non-syncope group Characteristics Syncope (n = 50) (%) Non-syncope (n = 50) (%) P Value MOCA impaired 33 (66) 16 (32) 0.001 HMSE impaired 28 (56) 13 (26) 0.002 Frailty 40 (80) 29 (58) 0.017 BADL impaired 33 (66) 25 (50) 0.073 IADL impaired 38 (74) 31 (62) 0.089 GDS short form (>=5) 31 (62) 22 (44) 0.071 Fall 12 (24) 5 (10) 0.062 Fear of fall 17 (34) 9 (18) 0.068 Urinary incontinence 22 (44) 22 (44) 1.000 MNA-SF Malnourished (0-7) 2 (4) 0 (0) 0.261 At the risk of malnutrition (8-11) 15 (30) 12 (24) Normal (12-14) 33 (66) 38 (76) Polypharmacy (>=5 drugs) 40 (80) 36 (72) 0.349 Vision impairment 26 (52) 34 (68) 0.102 Hearing impairment 43 (86) 33 (66) 0.019 Note: P Value calculated using Chi-square. Bold indicates that there was significant difference between syncope and non syncope group. Univariate analysis with syncope as dependent variable showed there was significant association with coronary artery disease, cognitive impairment, hearing impairment, frailty, and presence of four or more comorbidities. On further multivariate analysis, significant association of syncope was only observed with cognitive impairment, hearing impairment, and presence of four or more comorbidities (Table 4). TABLE 4 Univariate and multivariate regression analysis of various covariates with syncope Variables Univariate analysis Multivariate analysis OR (95% CI) P Value OR (95% CI) P Value Age 1.0 (0.91-1.09) 1.000 Sex 1 (reference) 1.0 (0.37-2.66) 1.000 Comorbidities CAD 2.57 (1.12-5.89) 0.026 1.69 (0.61-4.67) 0.313 HTN 0.83 (0.35-1.95) 0.663 DM 2.24 (0.96-5.19) 0.061 CKD 2.13 (0.50-9.07) 0.303 Arthritis 0.71 (0.32-1.60) 0.411 Anemia 1.29 (0.57-2.92) 0.535 COPD 0.71 (0.28-1.82) 0.477 Cancer 4.26 (0.46-39.54) 0.202 Habits Smoking 1.78 (0.75-4.24) 0.193 Alcohol 1.78 (0.75-4.25) 0.193 Geriatric syndromes BADL 1 (reference) 1.94 (0.87-4.34) 0.107 IADL 1 (reference) 1.94 (0.82-4.61) 0.133 MoCA 1 (reference) 4.12 (1.79-9.49) 0.001 6.47 (2.21-18.91) 0.001 MNA-SF 1(reference) 1.63 (0.68-3.91) 0.272 Vision 0.51 (0.23-1.15) 0.104 Hearing 3.16 (1.18-8.52) 0.023 6.21 (1.79-21.53) 0.004 Urinary incontinence 1.00 (0.45-2.20) 1.00 Polypharmacy 1.55 (0.61-3.93) 0.351 Frailty 2.89 (1.18-7.07) 0.019 1.54 (0.52-4.56) 0.440 Constipation 0.78 (0.35-1.73) 0.542 GDS 1 (reference) 2.07 (0.93-4.61) 0.073 Comorbidities 1 (reference) 4.75 (2.01-11.24) <0.001 6.29 (2.08-18.99) 0.001 Falls 2.84 (0.92-8.79) 0.070 Fear of falls 2.35 (0.93-5.94) 0.072 Note: Bold indicates Significant in univariate and multivariate analysis. 4 DISCUSSION In this study, we evaluated the etiology of recurrent syncope in the very old (75 years and older) and its association with various geriatric syndromes. The mean age of the population being 80 years formed a relatively old cohort for the Indian standard of life expectancy, which is 69 years. 19 Finding the etiology of syncope in the elderly is challenging as the events are frequently unwitnessed and the patients are less likely to have prodromal symptoms, may have amnesia for loss of consciousness, and it could be multifactorial. The prevalence of cardiac disease (arrhythmias and structural heart diseases) rises dramatically with age and hence the incidence of cardiac syncope also increases with age. 20 Cardiac rhythm disturbance is the most common cause of cardiovascular syncope and is responsible for approximately 20% of syncopal episodes in the elderly. 21 Also in this study, arrhythmias were found to be the most common etiology followed by valvular heart disease. Aortic stenosis predominated valvular heart disease. As age advances, the incidence of degenerative valvular lesions increases. Epidemiological studies have determined that more than one in eight people aged 75 and older have moderate or severe aortic stenosis (AS). Presyncope and syncope are common symptoms of AS and are also associated with the severity of aortic stenosis. The prevalence of moderate AS is to be consistently estimated at ~2% among individuals aged 70 to 80 years, with the prevalence increasing to 3% to 9% after the age of 80 years. In the US population-based series by Nkomo and colleagues, the prevalence of AS was strongly associated with age, with an odds ratio of 2.5 (95% CI 2.0-3.1) per decade of increasing age. 22 Coronary artery disease is known to be associated with aortic stenosis as well as myocardial infarction and is also seen to be associated with syncope. 23 In this study, we found a significant association between coronary artery disease and syncope as compared with non-syncope subjects. In our study, we found that individuals with recurrent syncope were four times more likely to have cognitive impairment. Older adults have a diminished cerebrovascular reserve and autoregulation and the occurrence of syncope in them results in a further decrease in cerebral blood flow resulting in unrelenting cerebral hypoperfusion. When this cerebral hypoperfusion is below a certain threshold, i.e., critically attained threshold of cerebral hypoperfusion (CATCH), it results in changes in brain microvasculature and causes metabolic energy crisis leading to ischemic injury of neurons, which results in progressive neurodegenerative and atrophic changes in the brain. This metabolic crisis accelerates oxidative stress and pro-inflammatory mechanisms, which results in increased amyloid beta deposition, aberrant protein synthesis, and disrupts synaptic plasticity leading to cognitive decline in the patient. In animal models, transient hypotensive episodes following bilateral carotid occlusion reduce synaptic plasticity and exacerbate both cognitive and motor dysfunction. Intriguingly, the cognitive deficits after permanent carotid occlusion are associated with elevated amyloid beta in the brain. 4 , 24 , 25 , 26 Frewen et al. studied the association of syncope and cognitive impairment in The Irish longitudinal study on aging (TILDA) and found that those participants with syncope and or non-accidental falls in the previous year had a poor global cognitive performance in comparison to the controls. 27 The prevalence of hearing impairment was 76% in our study population (86% in syncope group, 66% in non-syncope group). As observed previously, the prevalence of hearing impairment increases with age. Sharma et al. 28 found a prevalence of 81.4% in patients aged 80 years or older. Hearing impairment was significantly higher in the recurrent syncope group. This may be because of the reduced vascular supply to the inner ear. The cochlea is supplied by labyrinthine artery, which is an end branch of the vertebrobasilar system and hence it is sensitive to any restrictions in local and systemic circulation. Common systemic cardiovascular diseases are observed to be associated with hearing loss especially in elderly patients. It has been observed that patients with hearing loss of unknown etiology have been found eight times more prone to have concomitant ischemic heart disease than their healthy peers. It has been studied that 60% decrease in cerebral blood flow is known to cause TTS (temporary threshold shift) by means of cochlear hypoxia. Certain commonly used cardiovascular drugs like diuretics and beta blockers are associated with hearing loss as well. 29 , 30 Multimorbidity, defined as the presence of two or more comorbid conditions, is a growing public health challenge, particularly in the elderly. In our study, multimorbidity was present in 100% and 92% of the participants in the syncope and non-syncope group. Previous studies have reported an overall prevalence of multimorbidity between 24% and 83%. 31 , 32 On further analysis, a higher number of comorbidities was significantly associated with recurrent syncope in our study. With advancing age, there are blunted adaptive responses, contracted blood volume, age-related diastolic dysfunction, and other organ-related homeostenosis, and an increasing number of comorbidities increases the likelihood of being frail and polypharmacy. Polypharmacy was observed in 80% of subjects with syncope as compared to 72% in subjects without syncope though it was not statistically significant. Age-related physiological changes, comorbidities, and concomitant medication use also increase the risk of syncope. 3 In our study, multimorbidity, frailty and polypharmacy were also higher in the recurrent syncope group, but statistically significant association was found only with presence of four or more comorbidities on multivariate analysis. Syncope most often presents with a history of fall. Syncope has been seen to be strongly associated with fear of fall (FoF) as well. In our study, fall and FoF were found to be more in the recurrent syncope subjects, though not statistically significant. This may be because, as observed previously, only about 20% of cardiovascular syncope in patients older than 70 appears as a fall. 33 As cardiovascular syncope was the most common etiology in our study, it might have been a reason for majority of recurrent syncope group to experience a transient LOC but not experience a fall. This study has strengths and limitations like any other cross-sectional study. We have enrolled patients from a tertiary care center, which caters to and represents a heterogeneous population. Both outpatient and inpatients were included in the study, the geriatric syndrome prevalence may be higher in inpatients, but as inpatients were also included in the control group, there is no significant difference. Due to limited resources and time constraints, sequential evaluation was chosen for this study; multifactorial causation might be missed due to this approach. The sample size of the study was small; thus, the study findings cannot be well extrapolated to the general population. This study is a cross-sectional study, hence a longitudinal study should be done to establish the causal relationship between the syncope and decline in physiological reserve. 5 CONCLUSION Recurrent syncope is strongly associated with cognitive impairment, presence of four or more comorbidities, and hearing impairment. Conduction abnormality was the most common etiology of recurrent cardiovascular syncope, which is treatable, thus preventing further syncopal episodes in older adults. Structured evaluation of syncope to identify the etiology of syncope and appropriate management of cardiovascular syncope might reduce the decline in physical, cognitive, and psychological reserve. AUTHOR CONTRIBUTIONS Kamal Bandhu is the Principal Investigator of this study. Dr Aparajit Ballav Dey designed the study and Akshata Rao and Sada Nand Dwivedi analyzed the data. Akshata Rao and Kamal Bandhu wrote the initial draft of the manuscript. Dr Dey, Ashima Nehra, and Avinash Chakrawarty critically revised the manuscript. All authors had responsibility for accuracy of the final content and read and approved the final manuscript. FUNDING INFORMATION This work was supported by the Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi as the post-graduate dissertation of Dr. Kamal Bandhu. CONFLICT OF INTEREST The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ETHICAL APPROVAL Ethical approval was obtained from the Institutional Ethics Committee (IESC/T-14/21.01.2015), and the study was conducted according to ethical guidelines established by the Declaration of Helsinki and Good Clinical Practice Guidelines. Informed consent was obtained from all participants. ACKNOWLEDGMENTS The authors are grateful to the patients for their consent and support to carry out this research work. |
PMC10000260 | The characteristics of the human pronuclei (PNs), which exist 16-22 h after fertilization, appear to serve as good indicators to evaluate the quality of human oocyte and embryo, and may reflect the status of female and male chromosome composition. Here, a quantitative PN measurement method that is generated by applying expert experience combined with deep learning from large annotated datasets is reported. After mathematic reconstruction of PNs, significant differences are obtained in chromosome-normal rate and chromosomal small errors such as copy number variants by comparing the size of the reconstructive female PN. After integrating the whole procedure of PN dynamics and adjusting for errors that occur during PN identification, the results are robust. Notably, all positive prediction results are obtained from the female propositus population. Thus, the size of female PNs may mirror the internal quality of the chromosomal integrity of the oocyte. Embryos that develop from zygotes with larger female PNs may have a reduced risk of copy number variations. In this study, it is found that an obvious relationship has been obtained between female pronuclei (PNs) and chromosome-normal rate in blastocyst-stage embryos, but not for male PNs. In the stratified analysis, this predictive value comes from female proband in pre-implantation genetic test for chromosomal structural rearrangements group, and quantitative pronuclear measurements could distinguish the smaller chromosomal errors but not larger errors. artificial intelligence expert experience deep learning mathematical models pre-implantation genetic tests pronuclei identification source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 J. Yang , Y. Wang , C. Li , W. Han , W. Liu , S. Xiong , Q. Zhang , K. Tong , G. Huang , X. Zhang , Variation of Female Pronucleus Reveals Oocyte or Embryo Chromosomal Copy Number Variations. Advanced Genetics 2023, 4 , 2200001. 10.1002/ggn2.202200001 pmc1 Introduction Human embryos begin with the fertilization of an oocyte by a sperm. A sperm binds to the oocyte and delivers its chromosomal DNA, triggering the beginning of a series of microscopic events in the zygote including the cortical granule reaction, which prevents poly-fertilization, expelling of the second polar body, and the formation and migration of two separate pronuclei (PNs) that carry the maternal and paternal chromosomes. The male and female PNs form in proximity to the zygote's surface. Then, they need to move inward in order to unite the paternal and maternal chromosomes on the first mitotic spindle. During PN migration from the periphery inward to the center of the zygote, the areas of both PNs increase gradually. Phenomena related to pronuclear and nucleolar movements were first described by Wright et al. Notions including pronuclear alignment and uneven/even numbers of chromosomes in the PN and nucleolus precursor bodies (NPBs) have been expressed in more distinct pronuclear scores and used as a means to select embryos based on the Z-score. The scores have been correlated with improved embryo development, increased pregnancy and implantation rate, and embryonic chromosomal content after the pre-implantation genetic test (PGT). However, some studies have disputed the effect of pronuclear scores for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), even if 1PN-derived blastocysts have similar neonatal results as 2PN-derived blastocysts. In theory, characteristics of the pronuclear stage may mirror the internal chromosomal integrity of the oocyte and the sperm. Meanwhile, developmental details such as disorder cleavage, embryonic fragment extrusion, uneven blastomeres, and abnormal morphokinetics during the post-zygote stage (cleavage, morula, and blastocyst stage) might reflect embryonic developmental dysfunction, mainly aneuploidy, and mosaicism. Due to the vague standard of methods (more than 6 scoring systems) in current pronuclear assessments, the effect of pronuclear scores remains unclear. The dynamic character of the PN, incongruent practice in IVF laboratories such as fertilization time and checking time, and the heterogeneity in patients make efficient qualitative classification for pronuclear assessment impossible. Here, we aim to construct a computer-assisted algorithm for quantitative analysis for pronuclear assessment in ICSI patients from time-lapse incubators and test its efficacy in the diagnosis of chromosomal integrity in oocytes or embryos. 2 Results Before the study, 13 149 handle-annotated 2NP images of 276 blastocysts from 83 couples were used for Mask R-CNN learning(R-CNN) learning to PN recognition and establishment of the algorithm for quantitative analysis for pronuclear assessment. In this study, 2146 embryos from 184 patients were cultured for blastocysts and 1238 of them formed blastocysts. Blastocyst-stage embryos with unclear PN frames, indistinguishable male/female PNs, or only one blastocyst, as well as all normal/abnormal PGTs, were excluded from the final analysis. In total, 155 couples with 790 blastocyst-stage embryos were included in the final analysis, with 412 and 378 embryos in the pre-implantation genetic test for aneuploidy (PGT-A) and pre-implantation genetic test for chromosome structural rearrangements (PGT-SR) subgroups, respectively . Figure 1 Flow chart. After Mask R-CNN learning of 13 419 images morphometrically labeled by two experienced embryologists defined as handle-annotated 2PN images (276 embryos from 83 couples), the number of frames for artificial intelligence (AI) automatic recognition reached 16 634 for this study. After comparison with the handle annotation database using 16 634 AI automatic recognized images, it was found that 3343 more images were mislabeled than the actual number of 2PN images (overestimated). In these 3343 images, 3192 images (95.48%) came from early-stage PNs (12 h post-insemination), the rest came from 12-14 h post-insemination and no images came from 14 h post-insemination. Additionally, 128 images were missing because of partial overlap of two PNs in late-stage PNs (14-22 h post-insemination) . Figure 2 PN developmental model and adjustment of coefficients. A total of 16 634 images from 276 embryos of 83 couples. A) The frames of AI automatic recognition and handle annotation. B) Assessment of pronucleus (PN) coefficients. a) All automatically recorded PN areas (the scatters in the figure) were included in the original fitting curve (green line). The lowest value was the original coefficient b1. The outlier PN areas of the first three frames (which have the highest variance) were deleted in the adjusted fitting curve (yellow line). 12 h post-insemination and 14 h post-insemination fitting curves (blue and red lines) are depicted based on the lower automatic PN recognition error rates in those stages, which makes it easier to distinguish based on the value of b1. b) Sometimes, errors in counting occurred in automatic PN recording, but all data with incorrect numbers of PNs (other than pink and green PN circles), such as 3PN (mislabeling a vacuole as a PN), were omitted in fitting curves. C) The identification of polar bodies (PBs) and female/male PN handle checking. Red arrow, the appearance of the second PB; yellow arrow, the appearance of the male PN; blue arrow, dubitable second PB. a) Easily distinguished PN frames, clear PB2, and suitable distances of female and male PN to PB2 (proportion: 75%). b) Difficult to distinguish PN frames due to the cumulus cell disturbance (proportion: 6%). c) Difficult to distinguish PN frames due to the overlap of female and male PNs (proportion: 5%). d) Difficult to distinguish PN frames due to the equidistance of female and male PNs to PB2 (proportion: 14%). Figure 2 Female PN reveals oocyte or embryo abnormality. The accuracy of distinguish PN numbers by Mask R-CNN learning for (0, 1, 2, 3) reached 80.06% [13 419/(13 419 + 3342 + 128)] in recognition of all PN stages, 97.9% [13 419/(13 419 + 3342 - 3192 + 128)] in recognition at 12 h post-insemination until PN disappearance, and 99.06% [13 419/(13 419 + 128)] at 14 h until PN disappearance. No error was found in AI boundary drawing of PNs after handle checking except for PN number recognition-related boundary errors (e.g., mismarking vacuoles as PNs). For above errors in female and male PN coefficient b1 calculation, original, adjusted (first and last three images deleted due to the high inaccuracy rate in recognition and high weight in the fitting curve model), 12 h post-insemination, and 14 h post-insemination values were extracted for effective testing. Then, 2146 embryos from 184 patients who have top-quality blastocysts for PGT were included in the data analysis. The baseline characteristics of patients and their IVF outcomes are shown in Table 1 . Table 1 Baseline characteristics of patients Patient characteristics Mean (SD)/percent Age at IVF cycle 30.55 +- 3.94 Retrieved oocytes 16.79 +- 6.81 AMH level 4.30 +- 2.77 FSH (basic) 5.59 +- 2.60 BMI 21.77 +- 2.76 Gn day 9.26 +- 1.56 Gn dose 1875.08 +- 622.27 MII oocyte 14.09 +- 6.20 Infertility diagnosis (%) Decreased ovarian reserve 2.17 (4/184) Habitual loss 9.23 (17/184) Male chromosome abnormality 35.87 (66/184) Female chromosome abnormality 32.07 (59/184) Uterine/fallopian tube factor 7.61 (14/184) Obstetric abnormality 5.43 (10/184) Unexplained 7.62 (14/184) IVF protocol (%) Gn-a 42.93 (79/184) Gn-ant 57.07 (105/184) John Wiley & Sons, Ltd. Different grades of PN identification are shown in Figure 2B. In total, 529 from 2146 zygotes (24.65%) underwent handle male/female PN reversal after computer marking and embryologist checking. Total frames of clear and distinguished 1655 2PN embryos reached 108 587 images and these images were included to explore the factors that impacted female and male PN areas. In total, 1644 embryos with 108 028 images were included for blastocyst formation analysis. Finally, 790 embryos with 52 479 images from 155 patients were included for the analysis of both areas of PNs and PGT results. No clinical or cell biological factors were correlated with the female PN coefficient b1 except for the male PN coefficient b1 (r = 0.75, P < 0.01, Table 2 ) and the distribution data of the pronuclear area showed significant heterogeneity in individual patients. This heterogeneity makes it impossible to find a normal range of coefficient b1 . For homogenized exploration of the correlation between PN area coefficient b1 and PGT results, ranking orders of male/female were employed for testing in every patient. In blastocyst formation analysis, 1064 zygotes successfully developed into blastocysts and 580 failed, and no significant relationship was observed between ranking order of the female or male PN coefficient b1 and blastocyst formation (Table 3 ). Table 2 Correlation between male and female pronuclear coefficient b1 Dependent variable: Female pronuclear (coefficient b1) Standard b P Male pronuclear 0.75 0.000 Gn day -0.08 0.092 Gn dose 0.08 0.051 AMH 0.02 0.409 BMI 0.07 0.200 FSH (basic) -0.01 0.755 Female age -0.04 0.095 MII oocytes number 0.04 0.232 Viable embryo number -0.06 0.064 Infertility diagnosis -0.02 0.322 IVF protocol 0.02 0.496 John Wiley & Sons, Ltd. Table 3 Chromosome-normal rate between blastocysts and embryos that failed to form blastocysts based on the rank of the pronucleus area coefficient b1 Rank Female Male Formed blastocyst Failed Formed blastocyst Failed 1 126/211 (59.7%) 85/211 (40.3%) 145 (63.04%) 85 (36.96%) 2 130/211 (61.6%) 81/211 (38.4%) 117 (63.59%) 67 (36.41%) 3 125/199 (62.8%) 74/199 (37.2%) 127 (61.65%) 79 (38.35%) 4 124/178 (69.7%) 54/178 (30.3%) 128 (63.05%) 75 (36.95%) 5 108/167 (64.7%) 59/167 (35.3%) 105 (61.4%) 66 (38.6%) 6 95/137 (69.3%) 42/137 (30.7%) 91 (67.41%) 44 (32.59%) 7 78/115 (67.8%) 37/115 (32.2%) 76 (71.03%) 31 (28.97%) 8 52/92 (56.5%) 40/92 (43.5%) 63 (71.59%) 25 (28.41%) 9 55/75 (73.3%) 20/75 (26.7%) 54 (72.97%) 20 (27.03%) 10 41/59 (69.5%) 18/59 (30.5%) 52 (73.24%) 19 (26.76%) >10 130/200 (65.0%) 70/200 (35.0%) 106 (60.57%) 69 (39.43%) Total 1064 580 1064 580 Pearson Chi-Square 12.94 7.18 P 0.227 0.712 John Wiley & Sons, Ltd. PGT results from transferable blastocysts have a U curve in the female age-dependent distribution . By the female PN original coefficient b1 ranking, chromosome normal rate ("chromosome-normal" and "sole mosaic" proportion in total embryos) in the blastocyst with biggest PN area (top 1) is much higher than that of the blastocyst with smallest PN (last 1) (58.06% versus 45.16%, OR = 1.68 [1.07-2.64], P = 0.031), and the chromosome-normal rate of the top 2 blastocysts is higher than that of the last 2 blastocysts but with no statistical difference (59.31% versus 50.49%, P = 0.091) (Table S1-1, Supporting Information). After adjusting for coefficient b1, the chromosome-normal rate in the top 1 blastocyst is much higher than that of the last blastocyst (58.71% versus 45.16%, OR = 1.73 [1.10-2.71], P = 0.023), and the chromosome-normal rate of the top 2 blastocysts is higher than that of the last 2 blastocysts but with no statistical difference (57.35% versus 50.00%, P = 0.164) (Table S1-2, Supporting Information). For coefficient b1 12 h post-insemination, the chromosome-normal rate in the top blastocyst is much higher than that of the last blastocyst (64.52% versus 43.23%, OR = 2.39 [1.51-3.77], P < 0.001], and the chromosome-normal rate in the top 2 blastocysts is higher than that of the last 2 blastocysts (63.73% versus 47.55%, OR = 1.94 [1.30-2.88], P = 0.001) (Table S1-3, Supporting Information). For coefficient b1 14 h post-insemination, the chromosome-normal rate in the ranking top blastocyst is much higher than that of the last blastocyst (66.45% versus 42.58%, OR = 2.61 [1.68-4.24], P < 0.001), and the chromosome-normal rate in the top 2 blastocysts is higher than that of the last 2 blastocysts (64.22% versus 48.04%, OR = 1.94 [1.31-2.89], P = 0.001) (Table S1-4, Supporting Information). The trend that the top blastocysts showed higher chromosome-normal rates can be observed in Table 4 and Figure 3A. However, for the male PN coefficient b1, no significant difference was observed . Table 4 Rate of chromosome-normal blastocysts by the female PN coefficient b1 Rank Origin Adjusted 12 h 14 h 1 90/155 (58.06) 90/155 (58.06) 99/155 (63.87) 102/155 (65.81) 2 79/155 (50.97) 75/155 (48.38) 82/155 (52.9) 79/155 (50.97) 3 78/138 (56.52) 82/138 (59.42) 69/138 (50) 70/138 (50.72) 4 46/107 (42.99) 47/107 (43.93) 50/107 (46.73) 49/107 (45.79) 5 40/81 (49.38) 39/81 (48.15) 37/81 (45.68) 40/81 (49.38) 6 33/56 (58.93) 33/56 (58.93) 31/56 (55.36) 29/56 (51.79) 7 23/37 (62.16) 23/37 (62.16) 17/37 (45.95) 23/37 (62.16) 8 13/25 (52) 14/25 (56) 17/25 (68) 14/25 (56) >8 16/36 (44.44) 15/36 (41.67) 16/36 (44.44) 12/36 (33.33) John Wiley & Sons, Ltd. Figure 3 Rate of chromosome-normal blastocysts by ranking of PN coefficient b1. A) The rate of chromosome-normal blastocysts by the ranking of female PN coefficient b1. *There is correlation between ranking of female PN coefficient b1 and chromosome-normal rates. The correlation coefficients used for Spearman correlation analysis were as follows: 0.058 (Adjust), 0.099 (12 h), 0.114 (14 h), and P-value < 0.01 (blastocysts, n = 790, and patients, n = 155). B) The rate of chromosome-normal blastocysts by the ranking of male PN coefficient b1. *There is no correlation between ranking of male PN coefficient b1 and chromosome-normal rates (in origin/adjust/12 h/14 h). For Spearman correlation analysis, P-value > 0.05 (patients, n = 155). In all patients without distinguishing PGT-A and PGT-SR, the first and last ranking order could be used to detect the chromosome-normal and sole mosaic embryos (46.45% versus 28.39% in chromosome-normal rate, 66.45% versus 42.58% in chromosome-normal plus mosaic rate) . No significant differences in chromosomal status were obtained by coefficient b1 ranking in the PGT-A population . However, in the PGT-SR population, the first order embryos in coefficient b1 ranking have higher chromosome-normal and sole mosaic rates than the last embryos (40.54% versus 21.62% in chromosome-normal rate, 66.22% versus 32.43% in chromosome-normal plus mosaic rate) . Relatively smaller chromosomal errors defined as "euploid with errors" and "sole deletion and/or duplication" were significantly different between first-order and last-order embryos, even with median-order embryos having a hierarchical difference (PGT 9.68% versus 15.41% versus 20%, PGT-SR 13.51% versus 26.92% versus 36.49%, respectively, P < 0.001) . For chromosomal error-stratified analysis of coefficient b1 at 14 h post-insemination, PGT-A and PGT-SR, "aneuploidy with errors" and "euploidy with errors" (and a more detailed error classification including "chromosome-normal," "sole mosaic," "sole aneuploidy," and mosaic forms, "sole deletion and/or duplication" and mosaic forms, and "complex chromosomal errors"), "embryo's chromosomal error coincident/inconsistent with female," and "embryo's chromosomal error coincident/inconsistent with male" are shown in Figure 4B,C (Tables S4-S9, Supporting Information). From the female propositus and embryo analysis in PGT-SR, coefficient b1 ranking has detection power in both coincident and inconsistent chromosomal errors , which implied inherited and novel errors in embryos, but no significant detection ability in male propositus and embryos . Figure 4 Correlation between PGT results and PNs coefficient b1 ranking. A) PGT results (blastocysts, n = 790, and patients, n = 155). B) PGT-A results (blastocysts, n = 378, and patients, n = 75). C) PGT-SR results (blastocysts, n = 412, and patients, n = 80). 3 Discussion A clear relationship was observed between female PNs and chromosome-normal rate in blastocyst-stage embryos for both the original and adjusted analysis, but not for male PNs. In the stratified analysis, female PNs in the PGT-SR group, but not in the PGT-A group, can be used to distinguish relatively small chromosomal errors, such as "deletion and/or duplication" and mosaic forms. Inherited and novel errors in embryos could be found using female PN ranking in female diagnosis of the PGT-SR group. The overall positive pool effect of female PN diagnosis of chromosomal errors might be caused by the PGT-SR subgroup. The negative result in PGT-A might be because of a high false-positive rate [abnormal trophectoderm (TE) but normal inner cell mass (ICM)] as well as a false-negative rate (normal TE but abnormal ICM) in this technique. From the PGT result, a high coincidence U curve has been found as previously reported, but a small difference between these studies is that our age-distributed samples were blastocyst-stage embryos, not oocytes. Thus, chromosomal errors occurred post-PN from the cleavage to the morula and the blastocyst stage, and potential embryo self-correction in a later stage could reduce the power of PN predictors. The previously reported results indicated that embryonic chromosomal abnormality is more likely to be caused by eggs, especially in meiosis, and female PN developmental quantification could unveil the potential correlation. Again, the results confirmed that the pronuclear stage may mirror the internal oocyte quality and chromosomal integrity. However, due to the low chromosomal error rate in sperm, male PNs had no predictive value. Thus, we excluded chromosomal mosaicism because the typical mitotic errors could not be associated with the PN stage, but the effects of mitotic errors will merge in blastocyst-stage embryos. In the earliest design of outcome measurements, the total chromosomal substance was classified as normal, deletion, and duplication, but no significant difference was obtained (Table S10, Supporting Information). Interestingly, when the outcome measure was changed into normal and abnormal, a clear difference was observed. The exact reason will be studied in further research. A higher correlation has been obtained between female and male PN coefficient b1, but no clinical or cell biological factor exhibited a similar correlation in subsequent analyses. The high heterogeneity of the PN coefficient b1 made it impossible to establish a normal and abnormal range in clinical practice. No relationship between female or male PN and blastocyst formation was found, revealing that protein and energy storage could be more important to the developmental viability of embryos than chromosomal normality, at least if chromosomal errors are not too big. The lack of NPB assessment in our model was the main drawback in predicting the occurrence of aneuploidy. From this perspective, our quantitative measurement method could assess the area of PNs and identify small chromosomal errors. Further study is needed to improve image quality and to develop an optimal deep learning algorithm to achieve NBP recognition. 4 Experimental Section The deep learning images were obtained from the ICSI cycles of 184 infertile couples requiring assisted reproductive technology (ART) therapy performed in 2019-2020 at the Reproductive and Genetic Institute of Chongqing in China. Infertility was diagnosed according to either female or male chromosomal/genomic abnormality PGT-SR, PGT-A, unexplained reason PGT-A, and tubal and pelvic factors combined with male chromosomal/genomic abnormality for ICSI and subsequent PGT-A. The study was approved by the medical ethics committee of Chongqing Health Center for Women and Children. The morphology parameters in early stage of human embryos assisted by AI were associated with genomic status (ID NO:2019-602). In total, 155 couples with 790 blastocyst-stage embryos were included in the final analysis, with 412 and 378 embryos in the PGT-A and PGT-SR subgroups, respectively . 4.1 Practices in ART Before the ovaries were stimulated with recombinant FSH (Gonal-F, Merck Serono, Switzerland), downregulation was performed using a GnRH agonist (Decapeptyl; Ferring, Switzerland). Next, hCG (Ovidrel; Merck Serono, Italy) was administered when at least three leading follicles attained a mean diameter of >18 mm. The flexible GnRH antagonist regimen included rFSH (Gonal-F; Serono, Aubonne, Switzerland) injection starting on day 2 of the menstrual cycle. The starting dose of rFSH was 75-300 IU daily and was customized according to the patient's age, body mass index, antral follicle count, and baseline E2, P, FSH, and LH concentrations. Cetrorelix acetate (Cetrotide; Merck Serono Ltd., Aubonne, Switzerland) was used as the GnRH antagonist. Treatment with rFSH and cetrorelix acetate was continued until the day of the final oocyte maturation trigger. Transvaginal oocyte retrieval was performed 36 h after hCG injection. Cumulus-enclosed oocytes were collected in 2.5 mL of IVF medium (G-IVF, Vitrolife Sweden AB, Sweden) and incubated at 37 degC under 5% O2 and 6% CO2 conditions for insemination. Furthermore, sperm cells with normal morphology were selected, immobilized, and then microinjected into the oocyte cytoplasm 2-4 h after oocyte retrieval. Injected oocytes were then transferred into G-1 (Vitrolife, Sweden) medium droplets and placed into microwells of a custom-made dish (EmbryoSlide, Vitrolife Sweden AB, Sweden) containing 50 mL of equilibrated G-1 (Vitrolife Sweden AB, Sweden) microdroplets over the microwells and covered with 2.5 mL of Ovoil (Vitrolife Sweden AB, Sweden). Subsequently, the dish was immediately stored in a time-lapse (TL) system (EmbryoScope, Vitrolife, Goteborg, Sweden). After 3 days of culture, the embryos were extracted and transferred to a new dish containing 50 mL of equilibrated G-2 (Vitrolife Sweden AB, Sweden) microdroplets over the microwells and covered with 2.5 mL of Ovoil (Vitrolife Sweden AB, Sweden). The TL image acquisition was set every 10-15 min at seven different focal planes for each embryo. Images (1280 x 1024 pixels) were acquired using a Leica 20 x 0.40 LWD Hoffman Modulation contrast objective specialized for 635-nm illumination. Transferable blastocysts were defined as follows: at least in the blastocyst stage at day 5 (120 h after ICSI) with moderate expansion, having easily discernible tightly compacted inner cell mass (ICM), and having trophectoderm (TE) either in many cells forming a cohesive epithelium or in few cells forming a loose epithelium. 4.2 TL Setting The data were multi-view Hoffmann modulation contrast (HMC) microscopic images of developing cells in 11 different focal segments (-75, -60, -45, -30, -15, 0, 15, 30, 45, 60, 75) taken every 15 min. HMC is a kind of oblique lighting technology commonly used in IVF. When oblique light irradiates the sample, it refracts and diffracts. The light line generates different shadows through the objective lens optical density regulator so that the surface of the transparent sample produces a light and shade difference to enhance the contrast. The diameter of EmbryoSlide (Vitrolife, Switzerland) was 250 mm. Therefore, the total area of the well was 49062.5 mm. The number of pixels of the well of the culture dish was measured in all the time-lapse images. The number of pixels inside the well was 16077.98 +- 192.35. The relationship between a pixel and its actual size was 1 pixel = 0.3275 mm. 4.3 Establishment of the Algorithm for Quantitative Analysis for Pronuclear Assessment 4.3.1 Pronuclear Annotation and Automatic Recognition and Labeling For the accurate measuring of PN edge and area, a pre-processing of TL images, a Laplacian-based method that could confirm the clearest focal plane from the 11 Z-stack images was employed for both training and calculating databases. In the training database, the edge of each structure (pellucid zone, oocyte membrane, and PNs) was labeled using different color lines by two experienced embryologists. Then, the expert experience of deep learning for recognizing perivitelline space and PN was performed by a mask region-convolutional neural network (Mask R-CNN), which allowed to easily estimate PN poses in the same framework. An abandoned mechanism was introduced to automatic PN recognition, and any abnormal images (0, 1, 3, or more than 3PN) in the frame sequence were discarded. For example, an incorrectly recognized 3PN image classified with all other 2PN images was detected 18 h after ICSI images, and so was discarded in subsequent analysis. Figure 5 Female pronuclei reveal oocyte or embryo abnormality in the fourth figure. *A total of 16 634 images from 276 embryos of 83 couples. A) Pronuclear annotation and automatic recognition and labeling by AI. B) The rules to distinguish pronuclei. C) The pronuclear labeling stability. a) Pronuclear formation until nuclear envelope breakdown, showing the entire process of pronuclear migration and envelope enlargement in the human zygote. Blue represents the male pronucleus (PN) and red represents the female PN. costh is the residual spin value between the lines through the center of the PN circle in each consecutive frame. costh > 0 is mandatory to ensure PN location. b) The difference in area between male and female PNs will exist from PN appearance until disappearance. This means that larger or smaller PNs will consistently exist and that the PN's sex could be determined in the early zygote stage. The curves of both male and female PNs were established first, and female and male curves were distinguished later. D) Explanation of coefficients in the models. After distinguishing female from male PNs, parameters of female PNs were extracted by the software (b1 and b2). b1 represents the fictitious area of the PN at the time of ICSI and b2 represents PN development. 4.3.2 Distinguishing Female and Male PNs Normally, two separate PNs appear at different times and positions inside the perivitelline space. Three main approaches can be employed for PN classification. First, the position of two separate PNs can be considered. The female PN was closer to the second polar body (PB) than the male PN. Second, the male PN appears earlier than the female PN, but the sequence of pronuclear appearance was hard to differentiate sometimes due to the image quality. Third, male PNs were larger than female PNs in the early zygote stage. However, due to the inherent limitations in automatic labeling, potential inaccurate labeling will be ignored in data outputting. The simpler the annotation, the higher the efficacy that might be obtained in practice. Thus, the PB was not employed as a feature for machine learning but for following handle checking and correction . Only the second and third methods were employed to distinguish PNs and for automatic PN identification, and the second method was employed before the third method for automatic PN identification . All pronuclear identifications by computer were confirmed and corrected by a senior embryologist, who did not know the PGT results. 4.3.3 The Pronuclear Labeling Stability In practice, after the orientation of female and male PNs, AI might produce errors when separately labeling and categorizing female or male PNs, so vector calculus discrimination through cosine similarity (costh > 0) was performed for PN location insurance in subsequence images . 4.3.4 Exponential Model for Coefficient Extraction Mathematical models were employed to describe the dynamic nature of pronuclear development, including linear, logarithmic, cosine, quadratic, and exponential functions. Finally, an exponential fitting equation f(x)=b1x b2 x was employed, and the key coefficient b1 was extracted from the model. The fitting degree (coefficient of correlation, R2) in the exponential model ranged from 98% to 99.99%, which means that the increase in PN area was fully consistent with the exponential model predictions(for other models of linear, logarithmic, cosine, and quadratic functions, all the R 2 value was <90%). 4.3.5 Explanation of Coefficients in Mathematical Models The high value of R2 implies that the development of the PN (from appearance to disappearance) complies with the exponential mathematical model. b1 represents the fictitious area of the PN at the time of ICSI (f(0)=b1x b20, where (f(timeofICSI,t=0)=b1x 1 and b20 =1) and b2 represents the PN development trend . From this model, any value of the PN area (from 6 to 22 h after ICSI) could be obtained. However, because b2 was 1 (original b2 mean +- SD: 1.04 +- 0.017, range 1.01 to 1.11), the object of the study was b1. 4.3.6 NPBs Consideration PN scoring was the assessment of the NPBs that were formed on the chromosomes that contain the DNA for the ribosomal genes and were involved in the formation of the nucleolus at later stages. A recent study reported that zygotes clustering nucleoli at the pronuclear interface were thought to be more likely to develop into healthy euploid embryos. But it was impossible to include NPBs in the model due to current image quality, as well as the continuous alterations in location, size, and movement of NPBs. 4.4 Chromosomal Detection in Blastocyst-Stage Embryos On day 5 (120 h after ICSI), embryos with visible blastocoele were considered blastocysts without considering the quality. Transferable blastocysts were defined as follows: at least in the blastocyst stage at day 5 with moderate expansion, having easily discernible tightly compacted ICM and having TE either in many cells forming a cohesive epithelium or in few cells forming a loose epithelium. Several TE cells were extracted for biopsy using mechanical blunt dissection. Following the biopsy, the cells were placed into 0.2-mL thinly walled tubes, which were sealed and frozen by placing them in a freezer at -20 degC before genetic screening. Single-cell, whole-genome amplification (WGA) with multiple annealing and looping-based amplification cycles (MALBAC) was used. WGA was performed on cleavage-stage blastomeres using MALBAC following the manufacturer's protocol (Catalog No. YK001B; Yikon Genomics). Cells were lysed by heating (20 min at 50 degC and 10 min at 80 degC) in 5 mL of lysis buffer. Then, 30 mL of the freshly prepared pre-amplification mix was added to each tube and the mixture was incubated at 94 degC for 3 min. Next, DNA was amplified using 8 cycles of 40 s at 20 degC, 40 s at 30 degC, 30 s at 40 degC, 30 s at 50 degC, 30 s at 60 degC, 4 min at 70 degC, 20 s at 95 degC, and 10 s at 58 degC and immediately placed on ice. 30 mL of the amplification reaction mix was then added to each tube and the mixture was incubated at 94 degC for 30 s, followed by 17 cycles of 20 s at 94 degC, 30 s at 58 degC, and 3 min at 72 degC. Low-coverage (0.3x), genome-sequenced MALBAC products were purified using a DNA purification kit to construct the DNA library. 4.5 Chromosomal Error Definition "Chromosome-normal" was defined as follows: subsequently developed embryos (blastocysts) were euploid, without genomic disorders of deletions and/or duplications (including microdeletions and/or -duplications), that is, 46 XN. "Sole mosaic" was defined as follows: subsequently developed embryos were partial cells with normal chromosomes and the others with abnormal chromosomes either with aneuploidy or without genomic disorders of deletions and/or duplications, that is, 46XN, + mosaic (22) (33%) or 46 XN, dup (16) (p13.3p13.13) (5.7 Mb) (mos, 50%). Because gametes' chromosomal abnormalities should not be the source of "sole mosaic," embryos with sole mosaic forms were considered mitotic chromosomal separation errors. Thus, in this study, "chromosome-normal" and "sole mosaic" were included in the same group in the results. "Sole aneuploidy" was defined as follows: subsequently developed embryos were aneuploid without any other errors, that is, 47, XN, +22(x3). "Sole deletion and/or duplication" indicates that embryos possess small (>10 Mb) or submicroscopic genomic deletions and/or duplications (1 kb to 10 Mb) without mosaic forms, for example, 46, XN, dup (16) (p13.3p13.13) (5.7 Mb). "Aneuploidy with errors" includes aneuploidy with any other solely chromosomal errors, that is, 47, XN, +22(x3), dup (16) (p13.3p13.13) (5.7 Mb) or 47, XN, +22(x3), +mosaic (22) (33%). "Euploidy with errors" includes "sole deletion and/or duplication" euploidy with any mosaic forms, that is, 46, XN, dup (16) (p13.3p13.13) (5.7 Mb), +mosaic (22) (33%). "Complex chromosomal errors" indicates aneuploidy with chromosomal deletion and/or duplication and mosaic forms, for example, 45, XN, (-21), +4q (q12q31.1, 89 Mb, x3), 9p (p20p21.1, 32 Mb, x1, mos, 50%). The other classification of chromosomal errors was explored based on the coincidence of embryos' and patients' (the prominent indication or propositus) chromosomal/genomic abnormalities in PGT-SR. The results were grouped as "embryo's chromosomal error coincident with female," "embryo's chromosomal error coincident with male," "embryo's chromosomal error inconsistent with female," "embryo's chromosomal error inconsistent with male," "sole mosaic embryo," and "chromosomal normal embryo." Coincident errors mean the embryos' chromosomes had complete or partial errors like female or male somatic chromosomes, that is, 46, XX, t(1,16)(q42:q12) in somatic cells and 46, XN, +1q (q42.12-qter, 23.9 m, x3), -16q (q12.1-q24.3, 39 m, x1) in the embryo. 4.6 Machine Learning Programming and Statistical Analysis PN machine learning (83 patients [276 blastocysts]), distinguishing female and male PNs, pronuclear labeling stability certainty, PN ranking order, and automatic mathematical model establishment were performed using Python 3.9.7 (downloaded from ). Continuous variables were expressed as mean with standard deviation (SD) and categorical data were expressed as rates. Outliers were considered as missing values. The heterogeneity test for continuous variables, the Chi-square test for trend comparison, Spearman correlation analysis, multiple regression, and multiple logistic regression for relationships were used as appropriate (155 patients [790 blastocysts]). P < 0.05 was considered to indicate statistical significance. All analyses were conducted using Stata version 15.1 (StataCorp LLC, College Station, TX, USA). 5 Conclusions We believe that this is the first report on automatic calculation and morphologic quantitative data extraction using expert experience in deep learning based on pronuclear characteristics in human embryos. It helps to advance the non-invasively evaluation of embryos. Further prospective, well-designed studies are needed to validate the availability of quantitative PN assessment in clinical practice. Conflict of Interest The authors declare no conflict of interest. Author Contributions J.Y. and Y.W. contributed equally to this work. C.L., W.H., G.H., and X.Z. contributed to conceptualization. J.Y., W.H., G.H., and X.Z. contributed to methodology. Y.W., C.L., and S.X. contributed to data curation. J.Y., Y.W., W.L., Q.Z., K.T., and X.Z. contributed to formal analysis. J.Y., C.L., W.H., and X.Z. contributed to visualization. W.L., S.X., and Q.Z. handled supervision. J.Y., Y.W., and X.Z. wrote the original draft. G.H. and X.Z. reviewed and edited the writing. Peer Review The peer review history for this article is available in the Supporting Information for this article. Supporting information Supporting Information Click here for additional data file. Supplementary Information: Record of Transparent Peer Review Click here for additional data file. Acknowledgements The authors declare that they received no funding in support for this research. Data Availability Statement Data and code supporting this work are openly available at GitHub, including a workflow as a Jupyter notebook ) and anonymized images of embryo development ). Additional imaging data and information on embryo donors cannot be shared for ethical and legal reasons. |
PMC10000262 | Although sample size calculations play an essential role in health research, published research often fails to report sample size selection. This study aims to explain the importance of sample size calculation and to provide considerations for determining sample size in a simplified manner. Approaches to sample size calculation according to study design are presented with examples in health research. For sample size estimation, researchers need to (1) provide information regarding the statistical analysis to be applied, (2) determine acceptable precision levels, (3) decide on study power, (4) specify the confidence level, and (5) determine the magnitude of practical significance differences (effect size). Most importantly, research team members need to engage in an open and realistic dialog on the appropriateness of the calculated sample size for the research question(s), available data records, research timeline, and cost. This study aims to further inform researchers and health practitioners interested in quantitative research, so as to improve their knowledge of sample size calculation. This review aims to explain the importance of sample size calculation and to provide considerations for determining sample size in a simplified manner. Five elements essential in sample size calculation are discussed, and practical examples are used. This study aims to further inform researchers and health practitioners interested in quantitative research, so as to improve their knowledge of sample size calculation. effect size power regression analysis sample size study design source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Althubaiti A . Sample size determination: A practical guide for health researchers. J Gen Fam Med. 2023;24 :72-78. 10.1002/jgf2.600 pmc1 INTRODUCTION In the initial stage of planning a research study, sample size calculation--or power calculation--answers the question, "How many participants or observations need to be included in this study?" If the sample size is low, the research outcome might not be reproducible. 1 Informal guidelines for sample size based on the experience of researchers are used in most research studies and may be sufficient, as is the case in pilot studies. 2 , 3 However, when funding or institutional review board approval is requested, review committees often expect an explicit justification of the sample size. An increasing number of academic journals have requested evidence of sample size calculation or specific requirements to be provided in the method section of a manuscript, and the calculation can be part of a checklist before submission to a journal. 4 , 5 In addition, when sample size calculation is not mentioned, reviewers may wonder whether the sample size is adequate. Despite the many instructional materials available on sample size calculation, as well as statistical background knowledge being increasingly common among practitioners, 6 sample size calculation can be very challenging for researchers. 1 In addition, although sample size calculation is requested as part of the method section of a manuscript, adding this requirement has not obviously increased the reporting of sample size. The aim of this methods review is to present the importance of sample size calculation and to highlight factors worth considering when describing the rationale for the selected sample size. The different equations for sample sizes are not illustrated here, as they are beyond the scope of this review. Instead, challenges relating to sample size calculations in health research are summarized. The remainder of this paper is organized as follows. In Section 2, some important terms are presented. Sections 3, 6 discuss sample size calculations according to various types of study designs. Finally, Section 7 offers some general recommendations. 2 SAMPLE SIZE: WHAT TO UNDERSTAND? Sample size calculation involves several statistical terms, a selection of which is provided below in Table Table S1. In the following sections, the basic concepts are discussed, and detailed guidance is provided for sample size calculation. 2.1 Expectations regarding sample size A sample size can be small, especially when investigating rare diseases or when the sampling technique is complicated and costly. 4 , 7 Most academic journals do not place limitations on sample sizes. 8 However, an insufficiently small sample size makes it challenging to reproduce the results and may produce high false negatives, which in turn undermine the scientific impact of the research. On the other hand, choosing to enlarge the sample size may be ethically unacceptable, particularly in Phase 1 studies, where human subjects are exposed to risks. Moreover, a very large sample size may lead to p-values less than the significance level even if the effect is not of practical or clinical importance (i.e., false positives). 9 Hence, sample size calculation is important for striking a balance between risk and benefit. 10 Researchers' focus should not be on producing large sample sizes. Instead, the focus should be on choosing an appropriately sized sample that achieves sufficient power so that statistical testing detects true positives, comprehensively reporting the analysis techniques and interpreting the results in terms of p-values, effect size, and confidence intervals. 8 , 11 2.2 Sample size calculation using software programs Sample size calculation need not be done manually, and there are several free-of-charge software tools that can assist in the calculation. For example, OpenEpi 12 (an open-source online calculator) and G*Power 13 (a statistical software package) are commonly used for sample size calculations. Wang and Ji 14 provide an online calculator for common studies in health research. PS Power and Sample Size Calculation 15 or Sample Size Calculator 16 are practical tools for power and sample size calculations in studies with dichotomous, continuous, or survival outcome measures. The support offered by these tools varies in terms of the type of interface and the mathematical formula or assumptions used for calculation. 17 , 18 , 19 , 20 2.3 Statistical analysis to be used is important in sample size calculation Predominantly, the sample size should be determined based on statistical analysis. 2 , 21 , 22 The type of analysis should be closely related to the study design, study objective, research question(s), or primary research outcome. Most sample size calculation software packages include the option to select the required statistical test related to the response or outcome variable(s), with each test requiring a different sample size. Therefore, if a comparison between two or more groups is required after estimating the frequency of a certain attribute in the population, the calculated sample size should be adjusted, in order to account for the types of statistical tests to be used in the comparison. This ensures that the final sample size is appropriately suited to the study's main objective(s) or hypotheses. 2.4 When possible, determine the effect size In studies examining the effect of an intervention/exposure or the difference(s) between two or more groups, the effect size must first be determined, in order to calculate an appropriate sample size. The effect size is defined as the minimum effect an intervention must have in order to be considered clinically or practically significant. 23 This is considered the most challenging step in sample size calculation. When the effect is small, identifying it and reaching an acceptable level of power requires a large sample. When the effect is large, it is easily identifiable; hence, a smaller sample size is sufficient. The size effect is mostly determined by experience or judgment. 24 It can also be estimated from previously implemented, well-designed studies (such as meta-analyze; see, for example, Thalheimer and Cook 25 for a simplified illustration on how to determine effect size from published research). An initial pilot study may determine the effect size for start-up studies if accompanied by conversations with experts in the field that provide useful information on adequate value for the effect size. In a pilot investigation, sample size calculation may not be required for the pilot sample. 26 An important approach worth considering here involves enrolling pilot study participants based on the inclusion and exclusion criteria of the planned larger study and then testing the feasibility of the methods. 27 , 28 Various solutions have been proposed for cases where effect sizes cannot be determined. Cohen 29 recommends using small, medium, and large effect sizes instead of specific values (i.e., standardized or unit-free effect size). For example, when the mean difference between two groups is of interest, and independent samples t-test is to be used, the standardized effect size is calculated as: Standardized effect size=difference betweentwomeansstandared deviation of response The difference between the two means is the difference in practical importance, and the standard deviation of the response is often estimated from similar previous studies. Figure 1 illustrates that a sample size can be based on a range of standardized effect sizes and powers (e.g., d = 0.2 [small], 0.5 [medium], or 0.8 [large]). If the aim is to compare the mean difference between two groups, and an effect size of 0.5 (medium) is used, the total sample size required to reach a power of 80% is 128 participants. Hence, 64 participants are included in each group. FIGURE 1 G*power sample size software is used. Tail(s) = two: Two-tailed t-test. Allocation ratio N2/N1: Intended relative number of participants in each of the comparison groups (e.g., 1 or 2). a err prob: The probability of type I error = 0.05. b err prob: The probability of type II error. By contrast, for a small effect, the total sample size required is 788 patients, with 394 patients in each group. The use of such arbitrary values is common in sample size calculations. 30 Although these values do not admit biological explanations, they are considered to have meaningful effects in most comparisons. However, researchers must note that these are arbitrary values, and must use their judgment to assess whether these values are acceptable in their field of research. 24 , 31 3 SAMPLE SIZES FOR DESCRIPTIVE STUDIES A descriptive study is "concerned with and designed only to describe the existing distribution of variables, without regard to causal or other hypothesis." 32 Such studies include case reports, case series, and cross-sectional (prevalence) studies. 33 In the latter, the objective is to describe a health phenomenon in a population at a particular point in time. The main parameter of interest is proportion\prevalence, where the variable of interest is a categorical variable. In descriptive studies, the research could also be interested in the mean, where the variable of interest is a continuous response variable. For example, studies estimating the average age of children with asthma visiting the emergency room in a given year, or the prevalence of hyponatremia among the elderly in a tertiary care center, are descriptive in nature. The steps for sample size calculation in such descriptive studies are provided in Figure 2. FIGURE 2 Elements of sample size calculation for descriptive studies. For example, a 95% confidence level indicates that the sample mean will not differ by more than a certain value from the true population mean in 95% of the repeatedly withdrawn samples from the same population. The margin of error (MoE) is a measure of the precision of an estimate. The smaller the allowed MoE, the larger the precision of our estimates and the larger the sample size. Note that the confidence interval = estimate of value of interest +- MoE. For example, if the prevalence of burnout is 15% in a sample of residents, then, for the larger population, it is estimated to be between 5% and 25% (allowing MoE of 10% on both sides). The standard deviation (SD) and the estimate of proportion can be obtained from previous studies. If no information regarding the SD is available, researchers can collect a pilot sample to estimate the value of SD, and use range/n, where n is the number of observations in the pilot study. 34 If that proportion is unknown, it is best to use a proportion close to what is expected; otherwise, a value of 0.5 is assumed to give a sufficiently large sample size. 35 However, this value is appropriate if the actual population proportion is between 10% and 90%; otherwise (for example, in the case of rare or common disease), caution should be taken when substituting the proportion, as a significantly larger sample size is required. 36 Note that population size is not needed as an input in most sample size calculations. The population can be defined by various elements, such as geographical, time frame, or social aspects. For example, if the prevalence of infection in a hospital's intensive care unit (ICU) department during the period between 2005 and 2012 is to be estimated, then the population is all the patients admitted to ICU during that period. In most studies, we aim to generalize the results to a larger population, although we are restricted to observing a specific population. Therefore, when estimating the sample size, population size is rarely important in medical research. 37 However, if the population is limited (e.g., in a study that evaluates an academic program, where the population is all students enrolled in the program), then the sample size equations can be adjusted for the population size. 37 , 38 , 39 The size of a finite population can be obtained from a database or records, or based on experience in the field, and is included in the sample size calculation. 4 SAMPLE SIZE FOR STUDIES COMPARING TWO GROUPS There are two main types of study in health research: observational and experimental. An important distinction between the two is that, in an observational study, the researcher does not impose any intervention and observes only to assess a current condition. In experimental studies, an intervention is performed/conducted, and its results are observed. When the aim is to compare two groups (intervention/control), the number of study participants should be equally divided between both groups, so as to attain the maximum power for the given sample size. Note, however, that this point is limited to interventional studies and does not apply to observational studies (prospective vs. retrospective). The minimum sample size per group must be calculated based on the statistical test used. However, in some fields of study, such as pharmacology or biological research, a minimum of five per group is recommended and considered acceptable by academic journals in the field. 4 Recommendations for minimum sample sizes for clinical studies suggest having at least 100 in each group. 40 However, recent advances in sample size calculation have challenged these recommendations and have investigated the potential of simulation-based methods. 41 , 42 Dividing participants equally between both groups might not be possible, for several reasons, e.g., costs or limited data on the treatment group in retrospective studies. In such cases, uneven groups are the best option at hand where the researcher will opt to increase the sample in one group (e.g., control) with available data. 43 Attention should be paid to the statistical data analysis to be used 44 and the method for reporting results. p-values are generally large (above 0.05) in such cases, 45 so reporting effect sizes 29 and mean or median with confidence intervals can be more effective in conveying the practical importance of the results. All in all, increasing the sample size increases the precision of estimates, so it is important to report these measures. 5 PROBABILITY AND NONPROBABILITY SAMPLING There are two types of sampling methods in research: probability (random) and nonprobability (nonrandom). In a probability sample, each unit has a known chance or probability of being selected. By contrast, in nonprobability sampling, units are withdrawn or chosen without specific probabilities. Probability sampling includes simple random sampling, systematic sampling, and stratified sampling. Nonprobability sampling includes convenience sampling and quota sampling. Probability sampling has the advantages of higher generalizability, greater representativeness of the population, and lower response bias than nonprobability sampling. 46 However, nonprobability sampling is the most commonly adopted type of sampling in clinical studies, survey statistics, and social research, due to its no-cost or for ethical reasons. 47 , 48 , 49 , 50 While calculating a sample size is important for the generalizability of results, estimating a sample size when using nonprobability sampling could be irrelevant, as convenience sampling is likely to generate nongeneralizable results, which preclude statistical inference to the larger population. As an alternative, researchers should include as many subjects as possible 51 from the different subgroups and demographics. The quota sampling approach--or sample matching--might well be applied to minimize the selection bias often associated with nonprobability sampling. 52 This is particularly useful if the hypothesis states that the main outcome of interest differs based on specific factors or exposure, such as gender or age group. The use of replication research studies to validate the results of nonprobability sampling is also encouraged as a strategy for ensuring generalizability. 53 The methods section of a manuscript should include the number of subjects invited to participate or the size of target population (if known) and the number of participants instead of an actual sample size calculation. 49 For a review on the inferential data analysis methods for nonprobability sampling, see Buelens, Burger, and van den Brakel, 46 who applied machine learning methods in order to enhance the representativeness of the beforementioned sampling. 6 SAMPLE SIZE CALCULATION FOR REGRESSION ANALYSIS Correlation or regression analysis is used in studies aiming to examine associations between a set of independent variables and a response variable. Failing to include an appropriate number of observations leads to an insufficient sample size, in which case regression might overfit the data. 54 This means that, while the results may be valid for the study's dataset, they cannot be generalized to the population. In addition, estimates of regression coefficients are likely to be biased from true values, and the confidence intervals are large. 1 , 11 All these factors adversely affect statistical power. For regression analysis, several theories on sample size calculation have been provided in the literature regarding the use of logistic or linear regression for data fitting. 55 , 56 , 57 The number of predictors is important for sample size calculation in regression analysis. A larger sample size is required for a higher number of predictors. In cases where interaction terms have more than two predictors, the number of interaction terms and the degree of interaction can become large. When the sample size is not large enough to conduct a similar regression analysis, one might add only important interaction terms with a large effect or use practical judgment to form the interaction terms. Another important element in sample size calculation is the R-squared, defined as the measure of the strength of association between the regression model and the response; it is also defined as the proportion of the variance in the response that is explained collectively by the independent variables. 58 Calculating the sample size required for multiple regression analysis is equivalent to ascertaining the number of subjects to be enrolled to produce an acceptable R-squared or goodness-of-fit. Multiple regression analysis aims to determine whether a variable is significantly associated with the outcome after controlling for all the other predictors. For purposes of estimating the effect size in multiple regressions of each variable, an assumption is made regarding the value of the R-squared, because the exact estimates of regression coefficients of these variables are unknown. It is then possible to calculate Cohen's f 2 effect size, which is defined as the ratio of the proportion of variance accounted for relative to the proportion of a variable unaccounted for, where f 2 is classified as small, medium, or large (f 2 = 0.02, 0.15 or 0.35, respectively) effect sizes. 29 Calculating sample size on the assumption that regression analysis is to be used is not practical in many cases. For example, in any study, there may be more than one multiple regression model, and estimating the sample size for each model is not practical. Although it is common practice to estimate a sample size sufficient to estimate the minimum effect size, a minimum effect size might not be identifiable in some cases. Hence, researchers have often relied on "rules-of-thumb" to determine approximate sample sizes. For example, one of the considered rules-of-thumb calls for 10 observations per variable. 59 In addition, the sample size should be larger than the number of predictors, or else the regression coefficient cannot be estimated. How much larger the sample size needs to be is an issue of debate and depends on the field of study, e.g., biological or social research. Green 60 challenges most of the commonly used rules and argues for an approach that considers the effect sizes. While he has provided some support for the latter, he also argues that it is not appropriate when dealing with seven or more model predictors, though it is suitable when there is a medium-sized association between the response and predictors. More recent proposals in sample size determination reportedly overcome the design or practical challenges in the field. 7 , 59 7 GENERAL RECOMMENDATIONS 7.1 Account for nonresponsiveness Researchers must face the reality that not all invited participants are willing to be enrolled, which entails the possibility of a low response rate. A large difference between the calculated sample size and actual number of subjects in a study affects the generalizability of the results. Furthermore, the sample collected might not be large enough for the planned statistical analysis. Researchers often predict the response rate. For example, in clinical research, the dropout or noncompliance rate is around 10%. 61 Accounting for dropout or nonresponsiveness is particularly important in many studies, such as longitudinal studies requiring follow-up trials/studies. 62 Suppose n participants are required in a study, but a percentage (p) are projected to dropout or are nonresponsive. In such a scenario, more subjects must be approached in order to achieve the planned sample size. Hence, the edited final sample size is nfinal=n1-p. The value of the response rate is often derived from experience or previous research. For example, to estimate the proportion of burnout in staff residents in a regional hospital, consider a sample with 15% burnout. Allowing for an MoE of 5% and a confidence level of 95%, the minimum sample size is 195.9. The recommended sample size can be set at 245, so as to allow for a 20% nonresponse rate. Note that a large nonresponse rate is assumed here, as the population involves physicians. 63 7.2 Avoid unrealistically large samples For start-up studies or studies where no previously established literature is available, we recommend opting for medium to large effect sizes and not setting sample sizes based on the minimum effect that would be of practical significance. The results of such studies can provide insights and useful information for future meta-analyses. This also applies if the research is an undergraduate project with limited resources. For example, a researcher comparing the incidence of a certain outcome between two independent groups might initially be interested in serious complications in patients exposed to two distinct surgical treatments. However, if this number is very small, a large sample size will be required. If resources allow, the researcher should perhaps investigate whether there is a sufficiently large number of surgeries in the current hospital; if there is not, it may be advisable to cover more centers. Alternatively, these researchers could alter their research question so that it is concerned with the incidence of any complications following the procedure, and not limited to serious complications. Hence, the required sample size would be smaller and more feasible. In short, researchers should always look at the sample size and judge whether it is reasonable and suited to their research question(s). 8 SUMMARY Sample size calculation is the principal component of a quantitative study. Ethical committees consider it a prerequisite for the approval of a research study. However, sample size calculation is challenging and often relies on certain assumptions, which are rarely accurate. Determining the required sample size should not be considered an answer to a research question. The final decision should be guided by cost and time limitations, as well as clinical or practical judgment. AUTHOR CONTRIBUTIONS Alaa Althubaiti involved in conceptualization, investigation, formal analysis, methodology, project administration, writing--original draft, and writing--review and editing. ETHICAL APPROVAL Ethical approval was waived by the Ethics Committee in view of the study type. PATIENT CONSENT STATEMENT None. CLINICAL TRIAL REGISTRATION None. CONFLICT OF INTEREST The authors have stated explicitly that there are no conflicts of interest in connection with this article. Supporting information Table S1 Click here for additional data file. DATA AVAILABILITY STATEMENT Data sharing not applicable--no new data generated. |
PMC10000265 | The Global Alliance for Genomics and Health (GA4GH) is developing a suite of coordinated standards for genomics for healthcare. The Phenopacket is a new GA4GH standard for sharing disease and phenotype information that characterizes an individual person, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. A detailed example is presented that illustrates how to use the schema to represent the clinical course of a patient with retinoblastoma, including demographic information, the clinical diagnosis, phenotypic features and clinical measurements, an examination of the extirpated tumor, therapies, and the results of genomic analysis. The Phenopacket Schema, together with other GA4GH data and technical standards, will enable data exchange and provide a foundation for the computational analysis of disease and phenotype information to improve our ability to diagnose and conduct research on all types of disorders, including cancer and rare diseases. The Global Alliance for Genomics and Health (GA4GH) is developing a suite of standards to enable genomic and related-health data sharing. The Phenopacket is a new GA4GH standard for sharing disease and phenotype information that characterizes an individual person or biosample, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. Here, a detailed example is presented. deep phenotyping FAIR data Global Alliance for Genomics and Health Human Phenotype Ontology Phenopacket Schema NIH 10.13039/100000002 NHGRI RM1HG010860 NHGRI 1R01HG011799-01 OD R24OD011883 NICHD 1R01HD103805-01 NIH NLM75N97019P00280 NHGRI 10.13039/100000051 U24HG011449 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 M. S. Ladewig , J. O. B. Jacobsen , A. H. Wagner , D. Danis , B. El Kassaby , M. Gargano , T. Groza , M. Baudis , R. Steinhaus , D. Seelow , N. E. Bechrakis , C. J. Mungall , P. N. Schofield , O. Elemento , L. Smith , J. A. McMurry , M. Munoz-Torres , M. A. Haendel , P. N. Robinson , GA4GH Phenopackets: A Practical Introduction. Advanced Genetics 2023, 4 , 2200016. 10.1002/ggn2.202200016 pmc1 Introduction The Global Alliance for Genomics and Health (GA4GH), a policy-framing and technical standards-setting organization, is developing a suite of coordinated standards to enable responsible genomic and related-health data sharing. The Phenopacket is a new GA4GH schema for sharing disease and phenotype information. A Phenopacket characterizes an individual person or biosample, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. The Phenopacket schema supports the FAIR principles (findable, accessible, interoperable, and reusable), and computability. Specifically, Phenopackets are designed to be both human and machine-interpretable, enabling computing operations and validation on the basis of defined relationships between diagnoses, lab measurements, and genotypic information. The Phenopacket schema enables comparison of sets of phenotypic attributes from individual patients. Such comparisons can aid in diagnosis and facilitate patient classification and stratification for identifying new diseases and treatments. The Phenopacket schema is designed to support interoperability between people, organizations, and systems that comprise the worldwide effort to understand human disease. The structure of the information in a phenopacket was designed for integration within clinical laboratories, journals, data repositories, patient registries, electronic health records (EHRs), and knowledge bases. Increasing the volume of computable data across a diversity of systems will support global disease analysis by integrating genotype, phenotype, and other multi-modal data for precision health applications. Because of the broad range of intended use cases and the large number of terminologies and ontologies in use by different communities, the Phenopacket Schema is intentionally flexible with respect to which elements are required and which terminologies or ontologies must be used. Nonetheless, a given hospital, project, or research consortium may wish to apply different constraints. For instance, a Mendelian genetics consortium might stipulate the use of Human Phenotype Ontology (HPO) terms to describe phenotypic abnormalities, and a cancer genomics consortium might require that each phenopacket have a biosample for a tumor biopsy in which National Cancer Institute Thesaurus (NCIT) terms are used to describe the histological features and other phenotypic characteristics. In this article, we demonstrate the features of the GA4GH Phenopacket based on a typical clinical case report of a child with retinoblastoma. Retinoblastoma is a malignant tumor of the developing retina that typically occurs in children. Retinoblastoma is the most common eye cancer in childhood, but still a relatively rare disease, occurring in approximately one in 16 000-18 000 live births worldwide. The most common presenting signs are white pupillary reflex (leukocoria) and squinting (strabismus). Most affected children are diagnosed before the age of 5 years. Standard examination methods include, in particular, ophthalmoscopy, sonography, and--especially for staging purposes--magnetic resonance imaging. The chance of recovery and of preservation of eyesight depends very much on the spread of the tumor inside and outside the eye. The main therapeutic goal is always to save the life of the patient, which means primarily a complete removal of the tumor, while clinical management aims to preserve the eyeball and as much of the vision as possible. Retinoblastoma can occur sporadically or as a Mendelian trait. According to the Knudson hypothesis, development of retinoblastoma is initiated if both RB1 alleles have acquired disease-causing mutations. In sporadic forms, both mutations occur in somatic cells; in heritable retinoblastoma, the first RB1 mutation is inherited and only the second mutation occurs as a somatic event. In some cases, the first mutation occurs de novo either as a germline variant or a somatic mosaic. The RB1 gene is located at chromosome 13q14. Some patients have large 13q deletions that contain the RB1 gene. Germline or de novo mosaic 13q deletions can involve the surrounding genes delineating a contiguous gene syndrome characterized by retinoblastoma, developmental anomalies, and facial dysmorphisms. Mosaicism results from postzygotic mutation that occurs during early embryonic development and can lead to germline or somatic mosaicism, potentially causing a less severe and/or variable phenotype compared with the equivalent constitutive mutation. 2 Basic Introduction to Protobuf The Phenopacket Schema is a data model that is represented using the open source protocol buffers framework developed by Google. Protocol buffers ("protobuf" for short) provide a language-neutral, platform-neutral, and extensible mechanism for serializing structured data. They are used extensively in inter-server communications as well as for archival storage of data on disk. The data schema is described in .proto files and specifies how data is to be serialized (stored) as a hierarchical structure with key-value pairs similar to JSON or XML. However, in contrast to these formats which are written in plain text, data that is encoded using protobuf can be exchanged in a memory-efficient binary format. The protobuf file can be converted by the protobuf compiler into many different computer languages, including Java and Python, which provides a widely used framework for working with phenopackets. Additionally, protobuf can easily be converted into JSON or YAML for human consumption. In protobuf terminology, a message is a data structure that can contain multiple fields. Messages can be combined hierarchically so that one message contains another message. The .proto files define the structure of messages and the data types of the fields, including integers, strings, floating point numbers, and timestamps . Figure 1 Phenopackets Protobuf message comparison. (a) Definition of OntologyClass, a data type in the Phenopacket Schema, in protobuf. (b) Representation of an instance of OntologyClass (representing the HPO term for neutropenia) in a YAML format. (c) Equivalent representation in JSON format. In this article, we present a detailed example that shows how to encode various kinds of clinical data using the Phenopacket Schema. We will not discuss computational tools for creating phenopackets, which include Java and Python frameworks available from the protobuf framework itself. For readability, we will display phenopacket data using YAML, an intentionally human-friendly data serialization language that is one of the many different formats in which Phenopackets can be represented including YAML, JSON, binary (protobuf), RDF, and SQL. YAML and JSON versions of the complete phenopacket presented here are available as Supplementary files 1 and 2. 3 Overall Structure of the Phenopacket The GA4GH Phenopacket Schema contains several optional elements to represent a case report. The current example uses many of the optional fields. The Phenopacket represents the entire case report with information about the patient (Individual), the clinical diagnosis (Disease), several phenotypic features (PhenotypicFeature), clinical measurements (Measurement), an examination of the extirpated tumor (Biosample), therapies (MedicalAction), and the results of genomic analysis (GenomicInterpretation) . Figure 2 Phenopacket Schema overview. The GA4GH Phenopacket Schema is a hierarchical structure that consists of two required fields, id and MetaData, as well as eight optional fields, Individual, Disease, Interpretation, Biosample, PhenotypicFeature, Measurement, MedicalAction, and files, each of which is discussed in this article. A detailed version of the schema, including elements from VRS/VRSATILE, is shown in ref. . Phenopacket Schema is capitalized as a proper noun to refer to the data schema, however one should write "phenopacket" in lower case when one is referring to a phenopacket that represents an individual case. The following examples illustrate common use cases but do not present all of the fields in the Phenopacket Schema. Comprehensive documentation is available online. This article does not cover how to create phenopackets computationally, although we touch on this topic in the Discussion. Instead, we present a detailed example that is intended to help implementers and users of phenopackets understand their scope and capabilities. 4 Retinoblastoma and Mosaic 13q Deletion: A Case Report For this example, we present a 6-month-old child with retinoblastoma owing to a de novo mosaic deletion on 13q involving multiple genes, including RB1. She first came to medical attention because of leukocoria, strabismus, and retinal detachment in her left eye. Diagnostic workup included whole-genome sequencing (WGS) of germline DNA, which led to the identification of the de novo 13q deletion. Treatment included first intra-arterial melphalan infusions, which had to be discontinued because of adverse effects (vasospasm). Treatment with a regimen of three chemotherapeutic agents was attempted, but removal of the affected eye (enucleation) became necessary because of lack of response to the regimen. Histological investigation of tissue from the enucleated eye revealed several typical findings including apoptotic and necrotic cells and Flexner-Wintersteiner rosettes. WGS of DNA from the tumor sample revealed a somatic single-nucleotide variant in RB1 ("second hit"). For demonstration purposes, some clinical features were added to the original case report. The following sections show how individual components (messages) of the Phenopacket Schema can be used to represent the clinical information from the case report. 5 Individual Each phenopacket describes one individual. In many cases, the individual is a patient or a proband of a study, but phenopackets can be used to represent information about controls as well. The subject of the phenopacket is represented by an Individual message that contains fields for an identifier, the date of birth or age at the latest clinical encounter, the vital status, the sex, gender, and karyotypic sex. The majority of fields in Individual (and of the other elements of the Phenopacket Schema) are optional and can be left out if no information is available or if the field is not relevant for the intended use case. For instance, the date of birth field should not be used if a phenopacket is intended to be shared, and the karyotypic sex element should only be used if the results of chromosome analysis are available. The age (or age range) of the individual can be represented in a number of ways, some of which preserve privacy and are intended for responsible data sharing, and some of which are more precise. If the phenopacket is not intended to be shared broadly and the birthdate and the date of the last encounter need to be recorded, a TimeStamp message can be used to represent this information precisely. In many cases, the birthdate will be omitted and the age can be represented using an ISO 8601 string. For instance, the age of 42 years, 7 months, and 13 days would be represented as P42Y7M13D. One can also represent the age as P42Y without specifying the month or days, or one can use an AgeRange message to indicate that the individual's age lies within a given range, which may be desirable to help preserve privacy. All information in a phenopacket refers to this individual. In the current case, the following information was provided about the patient in the original publication. "A 6-month-old girl conceived by in vitro fertilization (IVF) (own oocytes and anonymous donor sperm) was admitted to the hospital because of leukocoria and strabismus. Past medical history and physical examination were unremarkable except for clinodactyly of the right fifth finger. Indirect ophthalmoscopic examination and examination under anesthesia was performed by ophthalmologists. Orbital ultrasound and magnetic resonance imaging (MRI) scans showed a 14 x 13 x 11 mm left eye tumor located in the lower-external retinal side. Retinal detachment was also detected." The Phenopacket representation of the clinical information for this case is shown in Figures 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. The patient id is arbitrarily defined as "proband A". Based on the case report, several key features were included in the Phenopacket representation. We define the age of the patient as 6 months (P6M) and the sex as female. For the sake of example, we have indicated the karyotypic (chromosomal) sex of the proband, although chromosome analysis would not typically be performed for this clinical indication . Additionally, the gender field can be used to specify the self-identified gender of an individual using an ontology term, and the vitalStatus message can be used to indicate if a patient is alive or deceased . Figure 3 Phenopacket messages. This Figure as well as Figures 4, 5, 6, 7, 8, 9, 10, 11, 12 show excerpts of the phenopacket with line numbers added. (a) Line 1 shows the beginning of the phenopacket (in a YAML file that only contains a single phenopacket, line 1 would contain a "-" instead of "phenopacket"). Line 2 contains the identifier of the phenopacket, which is required to be present but whose syntax is arbitrary and generally should be specified by the application. Lines 3-9 show the Individual message. (b) An example vitalStatus message for another example patient (not related to the example) that indicates the time and cause of death as well as the survival time following the primary diagnosis. 6 PhenotypicFeature The PhenotypicFeature is the central element of the Phenopacket Schema. A PhenotypicFeature can be used to describe each phenotypic feature (often, but not necessarily, clinical abnormalities) including signs and symptoms, laboratory findings, imaging, and electrophysiological results, along with modifier and qualifier concepts. Each phenotypic feature is described using an ontology term. One can indicate whether a certain abnormality was excluded during the diagnostic process (e.g., whether a morphological cardiac defect was excluded by echocardiography), or optionally use other HPO terms to denote the severity of the phenotypic feature or add other modifiers that describe the frequency (e.g., number of occurrences of seizures per week), laterality (e.g., unilateral), or another pattern of a certain phenotypic feature in the patient being described. Finally, the onset (and if applicable the resolution) of specific features can be indicated . Figure 4 List of PhenotypicFeatures. Clinodactyly, which is not known to be related to retinoblastoma and is presumably an incidental finding, was noted at the age of 3 months (P3M). Leukocoria was noted at the age of 4 months, strabismus at the age of 5 months and 15 days, and retinal detachment at the age of 6 months. 7 Measurement The Measurement message is used to capture quantitative, ordinal (e.g., absent/present), or categorical measurements. For some applications such as phenotype-driven genomic diagnostics of rare disease, qualitative representations of phenotypic abnormalities are appropriate, e.g., "Ocular hypertension" (HP:0007906), which denotes an increase of the intraocular pressure that is 2 standard deviations or more above the population mean. For other use cases, such as following the development of some parameter over time, the original quantitative values may be preferable, and can be represented using the Measurement element. Eyes that harbor a retinoblastoma characteristically display increased intraocular pressure. In our example, the patient is noted to have an intraocular pressure of 25 mm Hg, which is above the normal range, observed in the eye affected by the retinoblastoma (left eye). Measurement messages can be used to represent normal measurements; for instance, in our example the right eye was not affected by retinoblastoma and displayed a normal intraocular pressure of 15 mm Hg, measured with the Perkins tonometer. Both measurements include the reference (normal) range of 10-21 mm Hg . Figure 5 Measurement. A) Measurements of intraocular pressure (IOP) in the left eye (lines 48-65) and right eye (lines 66-83). 8 Biosample A Biosample contains information about the examination of biological specimens from which the substrate molecules (e.g., genomic DNA, RNA, proteins) for molecular analyses (e.g., sequencing, array hybridisation, mass-spectrometry) are extracted. Examples would be a tissue biopsy, a single cell from a culture for single cell genome sequencing, or a protein fraction from a gradient centrifugation. Several instances (e.g., technical replicates) or types of experiments (e.g., genomic array as well as RNA-seq experiments) may refer to the same Biosample. In our example, the Biosample message contains information about the histology of a "retinoblastoma" (NCIT:C39853) removed by "enucleation" (NCIT:C48601) of the "left eye" (UBERON:0004548) and classified as "Retinoblastoma pT3 TNM Finding v8" (NCIT:C140720). Histology further showed a "Flexner-Wintersteiner rosette formation" typical of retinoblastoma, in addition to "Apoptosis and Necrosis" . Figure 6 Biosample. The id (line 85) is required and can be used to relate genomic interpretations to the biosample that corresponds tothe interpretation . Lines 86-88 represent the tissue of origin of the specimen, lines 89-95 represent phenotypic features of the specimen, and lines 96-108 represent a measurement taken of the maximal size of the tumor. Note that the same PhenotypicFeature and Measurement message definitions are used here as described above. The tumor progression field (lines 109-111) is used to specify whether a tumor is primary, metastatic, or recurrent. Lines 112-126 contain the pathological TNM (primary Tumor, lymph Nodes, distance Metastasis) assessment. Finally, lines 127-133 specify a File with results of whole genome sequencing performed on this tissue sample (See the section on File messages, below, for explanations). The interpretation based on this sequencing is presented in Figure 8. While a Biosample message could be used to describe routine blood or buccal swab samples used for analysis of germline DNA, if the specifics of the collected tissue are not deemed relevant for the analysis, the information can be omitted (in this case, the subjectOrBiosampleId of the relevant GenomicInterpretation element should be set to the proband id; see below). 9 Interpretation A Phenopacket can contain one or more Interpretation elements that specify interpretations of genomic findings. For instance, a report from a diagnostic laboratory about a variant interpreted to be causal for a certain Mendelian disease may be represented as an Interpretation element. Another example would be a report of an actionable somatic variant for which a targeted cancer therapy is available. As a GA4GH standard, the Phenopacket Schema integrates with and leverages other GA4GH standards when applicable. The Phenopacket Schema uses the computational precision of the GA4GH Variation Representation Specification (VRS) while maintaining the flexibility of describing variation using human-readable variant description formats such as SPDI (NCBI sequence, position, deletion and insertion model) and HGVS through collaborative development and adoption of the VRS Added Tools for Interoperable Loquacious Exchange (VRSATILE). VRSATILE provides two primary object classes that are used in the Phenopacket Schema: the VariationDescriptor and the GeneDescriptor. These descriptor classes allow the extension of computationally precise concepts (e.g., VRS alleles, HGNC gene identifiers) with common additional attributes for systems to describe these concepts (e.g., identifier cross-references, HGVS descriptions, gene symbols, and informative contexts such as variant zygosity). This collaborative framework bridges existing variant representation formats and implementations to the more computationally precise concepts enabled by VRS. In our example, the patient was found to have one mosaic 13q germline deletion and one somatic missense mutation. A phenopacket can contain one or more Interpretation messages, whereby each Interpretation refers to a single disease that is specified in the diagnosis field. The Interpretation contains a list of one or multiple GenomicInterpretation messages that contain information about genetic findings that support the diagnosis. In our case, the diagnosis is retinoblastoma, which is indicated by the corresponding NCIT ontology term. Each GenomicInterpretation has a mandatory subjectOrBiosampleId field that specifies either the id of the patient (which must be the same as the id used in the subject field) or the identifier of the Biospecimen (which must be identical with the id used in one of the Biosample messages of the same phenopacket). For simplicity, we present this finding of a mosaic 13q in our example case as the result of whole-genome sequencing with estimation of mosaicism, but other technologies such as DNA microarrays might be more likely to be used in current clinical settings . Figure 7 Interpretation and GenomicInterpretation (1). The first portion of the Interpretation message is shown, with the status of the interpretation (solved) on line 136, the diagnosis to which the interpretation refers on lines 137-140, and the list of GenomicInterpretations starting on line 141. The first of two GenomicInterpretations is shown in this Figure, describing the mosaic deletion on chromosome 13. The deletion is specified as a CopyNumber message, which indicates the chromosome (the corresponding NCBI RefSeq NC_000013.14 identifier is listed), start and end positions, and the copy number (1, corresponding to a loss of one of the two copies of RB1). The extensions field is used to specify additional information about variants, such as the degree of mosaicism (here) or the allele frequency in the second GenomicInterpretation. In our example, next-generation sequencing of the retinoblastoma tumor sample was performed with a gene panel to search for somatic variants. "Looking for second hit mutations in RB1, we applied a custom designed NGS panel (Onconano V2) that included the RB1, BCOR and CREBPP genes (among other 400 commonly mutated genes in pediatric cancer). The study detected only one pathogenic single-nucleotide variant, RB1 c.958C > T (p.Arg320Ter) (NM_000321.2 chromosomal position 13-48,941,648-C-T; allele frequency of 25%)." This variant is represented as a second GenomicInterpretation message . Figure 8 GenomicInterpretation (2). The GenomicInterpretation message uses the subjectOrBiosample field to indicate the source of the sequenced material. In this case, the source was the tumor specimen described in the Biosample message of Figure 6. The variant, whose id is indicated as the corresponding dbSNP accession number (rs121913300) is classified as pathogenic using ACMG criteria (ClinVar VCV000126824.9). Information about the genomic location of the variant is provided as an Allele message in lines 171-180. The corresponding HGVS expression is provided in the label field (line 181; in general, the label can contain arbitrary text). The GeneContext field indicates the affected gene with its Human Gene Nomenclature Committee identifier and gene symbol in lines 182-184. The corresponding variant call format (VCF) representation of the variant is shown in the VcfRecord message in lines 190-195. The zygosity of the variant is specified in the allelicState field. 10 Disease The Disease message refers to the clinical diagnosis of one or more diseases that the patient has. In our example, the diagnosis of grade E retinoblastoma was made based on the International Classification for Intraocular Retinoblastoma. The Disease message allows the reporting of one or more clinical TNM stages to indicate the extent of the primary tumor as well as potential nodal involvement (i.e., spread of malignant cells to regional or distal lymph nodes) and the detection or absence of distant metastases. In our example, a Retinoblastoma-specific term from the NCI Thesaurus is used to indicate that no evidence of metastasis was found . Figure 9 Disease message. Disease message describing the diagnosis, the stage, age of onset, and primary site of retinoblastoma in the patient. Clinical staging is based on information available prior to the initial definitive treatment. Pathologic staging includes clinical information and information obtained from pathologic examination of resected primary and, if applicable, regional lymph nodes. The Phenopacket Schema includes a field for clinical TNM codes in the Disease message, and an additional field for pathological TNM codes in the Biosample message . In cases where there is no disease diagnosis, the Disease message can be omitted. Alternatively, a general diagnosis can be indicated by choosing an ontology term that denotes a group of specific diseases. For instance, the initial clinical diagnosis of ciliopathy (MONDO:0005308) might be made in a child with clinical manifestations such as situs inversus and postaxial polydactyly. The genetic workup (which would be represented in the GenomicInterpretation message; see below) could describe the molecular diagnosis of Bardet-Biedl syndrome 17 (MONDO:0014445). 11 MedicalAction For cancer, infectious disease, rare disease, and many categories of common disease, precision-medicine approaches to treatment based on classification by genetic variants are rapidly gaining in importance. Consequently, clinical decision-making needs to integrate genomic research findings with structured information about treatments. The GA4GH Phenopacket Schema includes a hierarchical representation of medical actions including medications, procedures, and other actions taken for clinical management. The Treatment element represents administration of a pharmaceutical agent, broadly defined as prescription and over-the-counter medicines, vaccines, and other therapeutic agents such as monoclonal antibodies or CAR T-cell-therapy. In our example, the following treatments were described. "The patient received intraarterial melphalan but due to a local vasospasm in her left leg, the treatment was discontinued. Afterwards, four courses of conventional chemotherapy were administered (vincristine, carboplatin and etoposide). A partial response was achieved, but, despite chemotherapy, the disease progressed few weeks later and the affected eye was enucleated." The MedicalAction message describes actions taken for clinical management. Each message refers to a specific type of medical action using a Procedure, Treatment, RadiationTherapy, or TherapeuticRegimen message. Our example contains a Treatment message referring to the administration of melphalan (a chemotherapeutic drug), a TherapeuticRegimen message referring to the administration of a regimen of chemotherapeutics, and a Procedure message referring to enucleation, that is, the surgical removal of the affected eye . Figure 10 A list of three MedicalAction messages. The Treatment message (lines 220-250) refers to the intraarterial administration of melphalan. A single dose was administered on the indicated date to treat retinoblastoma with curative intent. Vasospasm occurred as an adverse drug effect which necessitated the termination of this treatment. The TherapeuticRegimen message (lines 251-267) refers to the administration of three chemotherapeutic drugs (carboplatin, etoposide, vincristine) according to standard protocols from the age of 7-8 months. The Procedure message (lines 268-283) describes the surgical removal of the affected eye. 11.1 Files The files field of the Phenopacket Schema contains a list of File messages, each of which specifies a file with the results of genomic sequencing or another investigation. In our example, there is a single file and its location on the hard disk is given under uri (Uniform Resource Identifier) . Figure 11 FIle message. The URI field contains Uniform Resource Identifier, that is, a string for locating a file on the internet or other network or a computer file system. The individualToFileIdentifiers field is a map from the identifier used in the phenopacket to those used in the VCF or another file. The fileAttributes field is a list of key value pairs used to specify the genome assembly and the file format. 12 MetaData The MetaData message is required to provide details about all of the ontologies and external references used in the Phenopacket. The resources field contains a list of Resource messages with one resource for each ontology or terminology and the corresponding version used to create the phenopacket . Figure 12 Phenopackets Metadata. The MetaData message contains information about each ontology used to provide terms in the phenopacket as well as the phenopacket version. Version 1 of the GA4GH standard was released in 2019 to elicit feedback from the community. Version 2 was developed on the basis of this feedback and is described here. 13 Pedigree This element is used to represent a pedigree to describe the family relationships of each sample along with their gender and phenotype (affected status). The information in this element can be used by programs for analysis of a multi-sample VCF file with exome or genome sequences of members of a family, some of whom are affected by a Mendelian disease. The Phenopacket Schema has implemented a PED-compatible data model to promote interoperability between existing PED files and PED software, but does not actually store a PED file. In rare disease diagnostics and research, it is common to perform whole-exome or genome sequencing on multiple family members including persons affected and unaffected by a disease in order to be able to apply cosegregation analysis to filter or prioritize the variants. The GA4GH Phenopacket Schema provides a Family message that can include one or more phenopacket messages as well as a representation of the corresponding PED file. Future versions will be integrated with the GA4GH Pedigree standard. An example Family message is shown in Figure S3, Supporting Information. An analogous Cohort message is provided to represent a group of individuals related in some phenotypic or genotypic aspect. 14 Discussion The VCF standard for storing genotyping data allowed a wide range of research groups to write software for analyzing such data. The GA4GH Phenopacket Schema aspires to be similarly transformative in the landscape of disease analysis using an aggregation of phenotype data with core clinical and histopathological information in conjunction with results from genomic data. The Phenopacket Schema was designed to support a number of use cases, including rare-disease diagnostics, supporting searches for samples relevant to a specific disease or condition in biobanks and databases, representation of longitudinal data in registries, providing a computational representation of published case reports, and other applications. This article provides an in-depth introduction to the representation of clinical data using the GA4GH Phenopacket Schema to annotate a patient with retinoblastoma. We focused on explanations of how the Phenopacket Schema represents clinical data. In practice, phenopackets will be constructed computationally. The protobuf framework automatically generates code for creating phenopackets in major programming languages including Java, Python, and C++. We show examples of how this can be done in Java and C++ in the main phenopacket schema repository and are preparing a Java library for validation and convenient construction of phenopackets that we will present separately. Additionally, the formats and standards developed for phenopackets are increasingly being adopted by other data discovery and exchange protocols such as the GA4GH Beacon API, as well as several tools and databases that consume or output phenopackets, thereby promoting a wider penetration of phenopackets standards and practices throughout biomedical research. The Phenopacket Schema is flexible and adaptable to local and domain-specific needs. Importantly, and as indicated in the example, the phenopacket standard encourages the use of hierarchical classification systems and vocabularies such as HPO, UBERON or the NCIT; however it does not specify which ontologies have to be used, permitting user groups exchanging data to select the most appropriate and information-rich terminologies. Although the example shown here was comprehensive, for many current analysis programs in use in human genetics, a simple list of HPO terms and a path to the VCF file is all that is required to run them. We anticipate that the GA4GH Phenopacket Schema will enable such programs to use additional information for computational variant prioritization, such as excluded features, age of onset, and measurements. The Phenopacket Schema represents numerous categories of data important for translational research and diagnostics (Table 1 provides a summary). The Phenopacket does not represent all relevant data; two notable omissions that may be addressed in future versions of the Phenopacket Schema are social determinants of health (SDoH) and environmental exposures. Table 1 Summary of top-level fields of a Phenopacket. With the exception of the id and the metadata, all fields are optional Field Intended use Id An application-specific identifier for the phenopacket subject Demographic information about the subject of the phenopacket (often a patient or proband) phenotypicFeatures List of PhenotypicFeature messages, each of which provides an ontology term and additional context to describe a phenotypic feature (symptoms, signs, laboratory, or imaging findings, etc.). measurements List of Measurement messages, each of which represents the primary results of a clinical measurement such as a laboratory test. In many cases, Measurement messages are used to store the numerical results of a test. biosamples List of Biosample messages, each of which represents clinical data about a biosample such as a biopsy. interpretations List of Interpretation messages, each of which represents the clinical interpretation of a genetic or genomic investigation such as whole-genome sequencing. diseases List of Disease messages, each of which represents a clinical diagnosis of a disease. medicalActions List of MedicalAction messages, each of which represents an action such as a treatment or clinical procedure taken for the clinical management of the subject of the phenopacket. files List of File messages, each of which represents a file with data or results from a genomic or analogous high-throughput investigation. This field is intended for investigations done on peripheral blood samples (corresponding to germline DNA in the case of whole-genome sequencing). Investigations performed on other samples should be represented within the corresponding Biosample message. metaData Information about ontologies and references used in the phenopacket. John Wiley & Sons, Ltd. In general, computational tools are required to create and use phenopackets. Although the Phenopacket Schema is a relatively new development, several tools are already available. PhenoTips ) is an open-source software tool for collecting and analyzing phenotypic information from probands or families with a suspected genetic condition. PhenoTips can be used to collect HPO terms and other information and can export the data as a phenopacket. SAMS (Symptom Annotation Made Simple) is a freely available web-based application that offers a number of features including the ability to create phenopackets on the fly or to export case-level data as phenopackets. Additionally, SAMS enables patients or relatives to enter data to be shared with physicians and offers an API that can be integrated into other applications. A software library called phenopacket-tools ) provides developers with resources to streamline the creation and validation of phenopackets. The Phenopacket provides a standard input format for these tools that will simplify computational analysis pipelines, especially if the steps in the pipeline include a comparison of the results of multiple tools. Exomiser, LIRICAL, Phen2Gene, and CADA can take Phenopackets as input files, and other analysis tools will soon accept phenotype data in Phenopacket format. As clinicians move from traditional clinical annotation practices towards more routine use of computationally powerful representations of concepts in medicine this flexibility will facilitate the development and adoption of a rapidly growing ecosystem of digital support tools, and will empower forward-looking computational multimodal data discovery and analysis. Genomic data will become ever more important in translational research and clinical care in the coming years and decades. The Phenopacket Schema represents a standard for capturing clinical data and integrating it with genomic data that will help to obtain the maximal utility of this data for understanding disease and developing precision medicine approaches to therapy. Conflict of Interest The authors declare no conflict of interest. Peer Review The peer review history for this article is available in the Supporting Information for this article. Supporting information Supporting Information Click here for additional data file. Supplementary Information: Record of Transparent Peer Review Click here for additional data file. Supplementary Information Click here for additional data file. Supplementary Information Click here for additional data file. Supplementary Information Click here for additional data file. Acknowledgements NIH NHGRI RM1HG010860, NIH NHGRI 1R01HG011799-01, NIH OD R24OD011883, NIH NICHD 1R01HD103805-01, NIH NLM contract #75N97019P00280. Support was provided by EU Horizon 2020 research and innovation programme grant agreement 779257 (SOLVE-RD). P.N.S. acknowledges the support of the Alan Turing Institute. Data Availability Statement The data that support the findings of this study are available in the supplementary material of this article. |
PMC10000267 | Anticancer peptides (ACPs) are rising as a new strategy for cancer therapy. However, traditional laboratory screening to find and identify novel ACPs from hundreds to thousands of peptides is costly and time consuming. Here, a sequential procedure is applied to identify candidate ACPs from a computer-generated peptide library inspired by alpha-lactalbumin, a milk protein with known anticancer properties. A total of 2688 distinct peptides, 5-25 amino acids in length, are generated from alpha-lactalbumin. In silico ACP screening using the physicochemical and structural filters and three machine learning models lead to the top candidate peptides ALA-A1 and ALA-A2. In vitro screening against five human cancer cell lines supports ALA-A2 as the positive hit. ALA-A2 selectively kills A549 lung cancer cells in a dose-dependent manner, with no hemolytic side effects, and acts as a cell penetrating peptide without membranolytic effects. Sequential window acquisition of all theorical fragment ions-proteomics and functional validation reveal that ALA-A2 induces autophagy to mediate lung cancer cell death. This approach to identify ALA-A2 is time and cost-effective. Further investigations are warranted to elucidate the exact intracellular targets of ALA-A2. Moreover, these findings support the use of larger computational peptide libraries built upon multiple proteins to further advance ACP research and development. This study describes a novel strategy for searching for a new anticancer peptide (ACP) by integrating the computational peptide library of alpha-lactalbumin with downstream in silico machine learning-based screening and in vitro experimental validation. The novel ACP, so-called ALA-A2, specifically kills lung adenocarcinoma cells through autophagy mediated cell death. anticancer peptides cytotoxic screening drug discovery lung adenocarcinoma machine learning peptide library SWATH-MS New Discovery and Frontier Research Grant of Mahidol UniversityNDFR19/2563 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 T. Lerksuthirat , P. On-yam , S. Chitphuk , W. Stitchantrakul , D. S. Newburg , A. L. Morrow , S. Hongeng , W. Chiangjong , S. Chutipongtanate , ALA-A2 Is a Novel Anticancer Peptide Inspired by Alpha-Lactalbumin: A Discovery from a Computational Peptide Library, In Silico Anticancer Peptide Screening and In Vitro Experimental Validation. Global Challenges 2023, 7 , 2200213. 10.1002/gch2.202200213 pmc1 Introduction Worldwide, cancer is a leading cause of premature death and a growing public health burden. Global cancer estimates indicate up to 19 million new cases and 10 million cancer deaths in 2020. Conventional cancer therapies, such as chemotherapy and radiation, frequently result in cancer resistance and a lack of tumor selectivity. More effective treatment agents are required to improve patient outcomes. Anticancer peptides (ACP) are sequences of amino acids of fewer than 25 amino acids in length that have a cytotoxic effect on cancer cells. The modes of action of ACPs can be divided into three categories: 1) membranolytic peptides that kill cancer cells through pore formation on the cellular membrane; 2) cell penetrating peptides that are rich in basic amino acids (arginine and lysine), leading to translocation and access to intracellular compartments to disturb cellular homeostasis; and 3) tumor-targeting peptides that directly interact with cancer-specific molecules to mediate cell death. Two major approaches of ACP discovery include activity-guided purification from biological or natural sources of interest, and experimental screening of an established peptide library, that is, antimicrobial peptides. In our hands, a new strategy of ACP screening based on bio-physico-chemical features and machine learning (ML) preference of the input peptides proved to be cost-effective for prioritizing candidates for experimental studies. A naturally occurring peptide library from human milk, a promising source for therapeutic peptide discovery, was generated by sequential peptide fractionation coupled with liquid chromatography-tandem mass spectrometry. Of 142 input peptides, in silico ACP screening with subsequent experimental validation identified an anti-leukemic peptide that selectively kills four distinct leukemic cell lines in vitro and three patient-derived leukemic cells ex vivo. However, the bottleneck of the overall workflow lies in the relatively small and limited peptide library. Unfortunately, expansion of the peptide library using traditional approaches is associated with significant time and budget constraints. To address this issue, we had proposed a large peptide library generated by a computational method to facilitate further discovery of ACP from human milk. Alpha-lactalbumin, a 16-kDa milk protein with 142 amino acids, when in a complex with oleic acid, selectively induces cancer cell death in vitro and in vivo. Named "human alpha-lactalbumin made lethal to tumor cells (HAMLET)", this complex is currently under investigation in an early phase clinical trial. The monomeric form of alpha-lactalbumin was reported to be inactive for anticancer activity, but alpha-lactalbumin could nevertheless provide a good lead for developing a computer-generated peptide library, followed by deployment of in silico ACP screening and experimental validation of ACP candidates. This study aimed to establish a workflow for discovery of novel ACPs from potential alpha-lactalbumin peptides. An R-based script was created to generate all possible peptides that could be derived from the amino acid sequence of alpha-lactalbumin. The ACP physicochemical and structural properties, as well as the ACP probabilities predicted by three different ML models, were used to prioritize the peptide candidates from the 2688-peptide library. Anticancer activities of the candidate peptides were experimentally measured in vitro against human cancer cell lines derived from lung, breast, colon, brain, and leukemia cancers. Their hemolytic side effects were tested using a red blood cell (RBC) lysis assay. Sequential window acquisition of all theorical fragment ions (SWATH)-proteomics was performed to determine a potential mechanism of action of the peptide candidate, followed by functional validation. This workflow resulted in discovery of a novel ACP that induces autophagy-associated cell death in a human lung cancer cell line. 2 Results This study investigated the utility of computer-based peptide library generation coupled with in silico ACP screening for prioritizing peptide candidates. The top predicted ACP candidates were tested in vitro for actual anticancer activity against various cancer cell lines and also evaluated for potential toxicity using a RBC lysis assay ex vivo. The overall workflow of this study is illustrated in Figure 1 . Figure 1 The entire workflow of ACP discovery from a computer-generated peptide library based on alpha-lactalbumin, in vivo ACP screening, and in vitro validation experiments. aa: amino acid; ACP: anticancer peptide. 2.1 Alpha-Lactalbumin Inspired Peptide Library Generation and In Silico ACP Screening Human alpha-lactalbumin (UniProt ID: P00709) is comprised of 142 amino acids. Here, 2688 unique peptides, ranging from 5 to 25 amino acids per peptide with stepping 1 amino acid each were generated from alpha-lactalbumin by using the peptide generator ALA2Pept. The distributions of the 2688 peptides based on physicochemical, structural, and ML probabilities are shown in Figure 2 . As expected, the numbers of computer-generated peptides were inverse to the peptide length . The net charge of peptides ranged from -6 to +3, with the electrically neutral peptides being the majority of this library . Most known ACPs have a positive charge, so the initial focus was on the peptides with +3 charge. A secondary structure prediction was performed on this subset of peptides with a +3 net charge. Of the 25 peptides (1% of the total 2688 peptides) with +3 net charge, 19 were predicted to have a-helical conformation (ACP-preferred structure) and 6 had a coil/sheet structure . Three distinct ML models (ACPred-FL, Anticp2.0, and mACPpred) revealed distinct, but complementary, distributions of the predicted ACPs . The ACP candidates were ranked by the consensus score (geometric mean) of the three ACP probabilities, and filtered against their physicochemical and structural properties. All peptide sequences and the results of in silico ACP screening of 2688 peptides are provided in Table S1, Supporting Information. Figure 2 The distributions of various characteristics of the 2688 peptides generated from alpha-lactalbumin. a) Numbers of peptides by length (5-25 amino acid residues). b) Numbers of peptides by the physicochemical charge property. c) Secondary structure of 25 peptides containing +3 net charges predicted by three ML models. d) ACP probabilities as predicted by three distinct ML models, that is, ACPred-FL, Anticp2.0, and mACPpred. 2.2 Cancer Cytotoxic Screening Indicates ALA-A2 as the Positive Hit The list of candidates selected for the peptide synthesis and experimental validations is shown in Table 1 and Figure 3a. The top two peptide candidates, ALA-A1 and ALA-A2, are indicated by the highest consensus score peptides with non-redundant sequence, having >=3 positive charges, and containing alpha-helical secondary structure. Based on the similarity of their amino acid sequences, ALA-A3 and ALA-A4 are included as the lower-ranked peptide comparators of ALA-A1 and ALA-A2, respectively. Figure 3b illustrates the positions of these peptides within the 3D structure of alpha-lactalbumin (PDB: 1b9o) generated by AlphaFold. ALA-A1 and ALA-A3 peptides are derived from the linear N-terminal chain, while ALA-A2 and ALA-A4 are presented as part of the external surface of the folded alpha-lactalbumin. Table 1 Physicochemical, structural, and machine learning properties of selected peptide ACP candidates ID Amino acid sequence Length Charge Structure Machine learning model Consensus score Prediction ACPred-FL AntiCp 2.0 mACP pred ALA-A1 RFFVPLFLVGILFPAILAKQFTK 23 3+ coil-helix-coil-helix 0.980 0.620 0.964 0.836 ACP ALA-A2 KLWCKSSQVPQSR 13 3+ helix-coil 0.992 0.480 0.798 0.724 ACP ALA-A3 RFFVPLFLVGILFPAILAKQFTKC 24 3+ helix-coil-helix 0.980 0.590 0.977 0.826 ACP ALA-A4 LFQISNKLWCKSSQVPQSRN 20 3+ coil 0.944 0.460 0.075 0.319 non-ACP BMP-S6 (positive control) FKCRRWQWRMKKLGAPSITCVR 22 7+ coil-helix 0.606 1.000 0.9848 0.842 ACP John Wiley & Sons, Ltd. Figure 3 In vitro cytotoxicity of the synthetic peptides against five human cancer cell lines. a) The amino acid sequences with the predicted secondary structures, net charges, and consensus scores of all synthetic peptides included for experimental validations. b) The positions of ALA-A1, -A2, -A3, and -A4 peptides (black) on the predicted structure (blue) and the crystal structure (pink; PDB:1b9o) of alpha-lactalbumin as visualized by UCSF chimera 1.15. Note that ALA-A3 and ALA-A4 have amino acid sequences that partially overlap with ALA-A1 and ALA-A2, respectively. c) Cancer cytotoxicity screening against five human cancer cell lines, including lung cancer (A549), colon cancer (HT29), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and leukemia (K562) cells. The synthetic peptides (200 mm) were incubated with cancer cells at 37 degC for 24 h before measuring cell viability (MTT assay). Only ALA-A2 exhibited a selective and substantial anticancer effect against A549 and HT29 cells. This experiment was performed in three biological replicates. *p < 0.05; N-ter: N-terminal; C-ter: C-terminal. To determine whether the in silico predicted candidates actually exhibit anticancer effects in vitro, the synthetic peptides were tested against five cancer cell lines . BMP-S6, a bovine-derived ACP from previous studies, was included as the positive control of this study. ALA-A2 (at 200 mm) selectively induced cancer cytotoxicity of A549 human lung epithelial adenocarcinoma (59.7 +- 1.1% cell viability) and HT29 human colorectal adenocarcinoma (55.3 +- 2.7% cell viability) cell lines, but did not affect K562 human lymphoblastic leukemia, MDA-MB-231 human breast cancer, and SH-SY5Y human neuroblastoma cell lines. ALA-A1, ALA-A3, and ALA-A4 did not exhibit a substantial anticancer effect against the five cell lines examined. BMP-S6 was the only peptide that exhibited cancer cytotoxicity against K562 leukemic cells, consistent with previous studies. Accordingly, ALA-A2 was designated the positive hit from in silico and in vitro ACP screening, and subjected to further validation. 2.3 Dose-Response Relationship, Hemolytic Side Effect, and Cell Internalization of ALA-A2 The dose dependency of ALA-A2 against A549 and HT29 cells was measured at twofold serial dilutions from 0 to 400 mm. Based on this dose testing range, the IC50 of A549 is 300 mm and the IC50 of HT29 is extrapolated to be greater than 1000 mm. The higher concentration of ALA-A2 doses resulted in lower cell viability of A549, and, to a lesser extent, of HT29 cells . Figure 4 Dose-dependent cytotoxicity, hemolytic side effect, and cell penetrating capability of ALA-A2 peptide. a) ALA-A2 dose-response relationship in A549 lung cancer and HT29 colon cancer cell lines. The cells were incubated with twofold dilutions of ALA-A2 from 400 to 0 mm for 24 h, and then cell viability was measured by the MTT assay. b) RBC lysis assay for ALA-A2 peptide toxicity testing. Human red blood cells were incubated with the peptides for 1 h. Triton X-100 at a final concentration of 1% was used as a positive control. c) Confocal microscopy showed that FITC-tagged ALA-A2 peptide (green) could internalize into A549 lung cancer cells without altered membrane integrity, whereas Triton X-100 (0.5% v/v; the positive control) could permeabilize cellular membrane allowing PI internalization (red). Hoechst 33342 (blue) was used for the nuclear counter staining. Scale bar: 50 mm. Hemolysis is a major concern during the development of peptide-based drugs; hemolytic peptides do not progress to clinical trials. Thus, hemolytic activity of the ACP ALA-A2 was compared with those of other peptides without anticancer activity. Figure 4b illustrates that neither ALA-A2 (200 mm) nor the other peptides exhibit hemolytic effects against normal RBCs after 1 h incubation. The percent hemolysis was ALA-A1, 5.6% +- 0.6%; ALA-A2, 7.8% +- 10.2%; ALA-A3, 1.3% +- 1.2%; ALA-A4, 0.7% +- 0.6%; and BMP-S6, 6.0% +- 9.2%. Note that 1% Triton X-100, the positive control, completely lysed the normal RBCs within 1 h. The anticancer mechanism of ALA-A2 was investigated in A549 lung cancer cells. Membranolysis and cell penetrating peptides are both common, but distinct, modes of ACP action. To explore the mode of action of ALA-A2, A549 lung cancer cells were treated with FITC-tagged ALA-A2 peptide (200 mm) for 24 h, followed by confocal microscopy. Figure 4c illustrates that the signals of FITC-tagged ALA-A2 were present in the intracellular compartments of A549 cells. ALA-A2 did not disrupt membrane integrity. Propidium iodide (PI) is internalized following treatment with Triton X-100, the positive control for a cell permeabilized agent, whereas it is not internalized following treatment with ALA-A2. Thus, ALA-A2 penetrates the cell and may be the trigger for cell death-related signaling of A549 lung cancer cells. 2.4 ALA-A2 Triggered Autophagy-Mediated Cell Death in A549 Lung Adenocarcinoma Cells SWATH-proteomics was performed to investigate potential mechanisms of the ALA-A2 anticancer effect in A549 lung cancer cells. Of 286 proteins detected and quantified across 18 data independent acquisition (DIA) runs (full data sets in Table S2, Supporting Information), heatmap and volcano plot revealed 38 differentially expressed proteins (12 upregulated and 26 downregulated) in ALA-A2 treated A549 cells . Reactome pathway enrichment analysis was performed to deduce biological meaning from this differential protein signature. Figure 5c demonstrates that the autophagy pathways, particularly chaperone-mediated autophagy, were the best matched pathway with the lowest false discovery rate (details in Table S3, Supporting Information). This functional match mostly reflected four downregulated proteins: ubiquitin-60S ribosomal protein L40 (fold-change = 0.41, p = 0.027), heat shock 70 kDa protein 8 (fold-change = 0.25, p = 0.006), and heat shock protein HSP90 alpha (fold-change = 0.26, p = 0.007) and beta (fold-change = 0.40, p = 0.004) . To confirm this deduction, the ability of ALA-A2 peptide (200 mm) to induce autophagy was tested. As shown in Figure 5d, ALA-A2 treatment significantly increased the autophagic activity in A549 cells (1.5-fold of untreated cells) comparable to that of rapamycin, a positive control known to induce autophagy. Taken together, these findings identified ALA-A2 as a cell penetrating peptide that induces autophagy-mediated cell death in A549 human lung adenocarcinoma cells. Figure 5 SWATH-proteomic and functional analyses suggest that cell death is caused by autophagic induction. a) Heatmap and b) volcano plot identified the significantly differentially expressed proteins between ALA-A2 peptide-treated versus untreated A549 cells (n = 9 per group; three technical replicates of three biological specimens) (full expression datasets in Table S2, Supporting Information). c) This reactome was subjected to biological pathway analyses. The stronger yellow accent indicates lower false-discovery rate. Chaperone mediated autophagy was predicted as the most significant pathway elicited in ALA-A2 peptide-treated A549 cells (details in Table S3, Supporting Information). d) Autophagy activity assay. Rapamycin, an autophagic inducer, was the positive control. This experiment was performed in three biological replicates. *p < 0.05. Table 2 Significantly differentially expressed proteins between ALA-A2 treated versus untreated A549 lung adenocarcinoma cells SwisProt ID Gene name Protein name %Coverage Number of matched peptides MW [kDa] pI Fold-change [treated/ untreated] p-value Proteins whose expression was upregulated in ALA-A2 treated cells Q13148 TADBP TAR DNA-binding protein 43 2.90 1 44.74 5.85 4.07 0.0348 Q9UKM9 RALY RNA-binding protein Raly (Autoantigen p542) 6.86 1 32.463 9.20 3.57 0.0209 P20073 ANXA7 Annexin A7 8.61 1 52.739 5.52 3.29 0.0011 O00299 CLIC1 Chloride intracellular channel protein 1 11.20 2 26.923 5.09 3.02 0.0212 P09525 ANXA4 Annexin A4 18.81 1 35.883 5.84 2.98 0.0074 Q02878 RL6 60S ribosomal protein L6 19.10 2 32.728 10.59 2.87 0.0319 P26639 SYTC Threonine-tRNA ligase 1 4.70 1 83.435 6.23 2.61 0.0100 P50991 TCPD T-complex protein 1 subunit delta 13.36 3 57.924 8.13 2.39 0.0255 Q99729 ROAA Heterogeneous nuclear ribonucleoprotein A/B 5.42 1 36.225 8.21 2.35 0.0248 O00410 IPO5 Importin-5 6.38 3 123.63 4.83 2.22 0.0010 P42704 LPPRC Leucine-rich PPR motif-containing protein 14.92 11 157.905 5.53 2.06 0.0091 P14923 PLAK Junction plakoglobin 7.52 2 81.745 5.75 2.05 0.0041 Proteins whose expression was downregulated in ALA-A2 treated cells Q6FI13 H2A2A Histone H2A type 2-A 62.31 19 14.095 10.90 0.48 0.0438 Q9NZL4 HPBP1 Hsp70-binding protein 1 8.36 2 39.303 5.13 0.48 0.0067 P49368 TCPG T-complex protein 1 subunit gamma 10.83 3 60.534 6.10 0.46 0.0336 P14618 KPYM Pyruvate kinase PKM 54.43 32 57.937 7.95 0.43 0.0258 P37837 TALDO Transaldolase 17.80 3 37.54 6.36 0.43 0.0089 P62987 UBA52 Ubiquitin-60S ribosomal protein L40 52.34 4 14.728 6.56 0.41 0.0272 P08238 HSP90AB1 Heat shock protein HSP90 beta 37.15 25 83.264 4.96 0.40 0.0039 P14625 ENPL Endoplasmin 17.68 10 92.469 4.73 0.38 0.0301 P29401 TKT Transketolase 39.33 20 67.878 7.58 0.35 0.0004 P05783 K1C18 Keratin, type I cytoskeletal 18 53.02 42 48.058 5.34 0.35 0.0149 P08727 K1C19 Keratin, type I cytoskeletal 19 23.75 7 44.106 5.05 0.34 0.0327 P84103 SRSF3 Serine/arginine-rich splicing factor 3 12.80 1 19.33 11.64 0.33 0.0102 P16402 H13 Histone H1.3 25.34 2 22.35 11.02 0.32 0.0227 P04406 G3P Glyceraldehyde-3-phosphate dehydrogenase 60.00 32 36.053 8.58 0.32 0.0088 P26641 EF1G Elongation factor 1-gamma 20.14 4 50.119 6.27 0.31 0.0123 O60218 AK1BA Aldo-keto reductase family 1 member B10 71.52 26 36.02 7.66 0.29 0.0120 P07437 TBB5 Tubulin beta chain 53.15 39 49.671 4.78 0.27 0.0041 P62805 H4 Histone H4 57.28 15 11.367 11.36 0.26 0.0302 Q06830 PRDX1 Peroxiredoxin-1 29.65 10 22.11 8.27 0.26 0.0190 P07900 HSP90AA1 Heat shock protein HSP90 alpha 37.02 24 84.66 4.94 0.26 0.0069 P22626 ROA2 Heterogeneous nuclear ribonucleoproteins A2/B1 24.93 3 37.43 8.97 0.25 0.0281 P11142 HSPA8 Heat shock 70 kDa protein 8 28.79 21 70.898 5.37 0.25 0.0056 P08865 RSSA 40S ribosomal protein SA 17.97 3 32.854 4.79 0.25 0.0285 Q5VTE0 EF1A3 Elongation factor 1-alpha-like 3 35.93 19 50.185 9.15 0.15 0.0061 P63261 ACTG Actin, cytoplasmic 2 63.20 53 41.793 5.31 0.09 0.0030 P21359 NF1 Neurofibromin 1.02 1 319.372 7.12 0.07 0.0030 John Wiley & Sons, Ltd. 3 Discussion The novel approach to ACP identification described in this study demonstrates that a computer-generated peptide library with downstream in silico ACP screening and in vitro experimental validation could accelerate anticancer research and development. Alpha-lactalbumin, a milk protein known for anticancer properties, inspired this study design. The library of 2688 distinct peptides containing 5-25 amino acids in length were generated from the sequence information of alpha-lactalbumin rapidly . As different ML models were established upon various data sets, algorithms, and tuning parameters, their predictive performance can vary. Rather than relying on only one ML model, we utilized the consensus score, which is a geometric mean of ACP probabilities of three different ML models, plus the physicochemical and structural properties, to obtain better ACP candidates. After in silico ACP screening of 2688 peptides, a few top-ranked candidates were achieved within days for the custom-ordered peptide synthesis and in vitro experimental validation . This study identified ALA-A2 as a novel ACP in a cost-effective manner. ALA-A2 was relatively selective to lung adenocarcinoma cells, acting as a cell penetrating peptide to induce autophagy-mediated cell death without provoking hemolysis. The sequence of ALA-A2 as KLWCKSSQVPQSR was predicted for its half-life in blood using PlifePred accessed on October 30, 2022) that remained 20 min in blood. Because of a relatively short half-life of ALA-A2 peptide, it should be modified, for example, by amidation at C-terminus, to improve the stability of ALA-A2 for further clinical applications. Moreover, the 200 mm ALA-A2 concentration was chosen to observe lung cancer cell responses because the effect of this dose was obvious on A549 cells. This high dose has no hemolytic effect while exhibiting lung cancer cytotoxicity through autophagy-induced cell death . Brisuda et al.[ 7a ] reported that the a-helical peptide (residues 1-39) derived from alpha-lactalbumin in complexes with oleate (so-called alpha1-oleate) had a tumoricidal effect against bladder cancer, but beta-sheet-oleate (residue at 40-80) complexes lacked anticancer properties. Both ALA-A1 and ALA-A3 partially overlapped with the alpha1-oleate, while ALA-A2 and ALA-A4 were part of the beta-sheet-oleate. However, the data reported herein indicate that only ALA-A2 exhibits the anticancer effect. This discrepancy may be due to the absence of oleate, the shorter length of ALA-peptides, and the different cancer cell lines examined in this study. Our computational workflow did not generate any peptide longer than 25 amino acid residues. By default, the bare peptides of alpha1-oleate (39 amino acids in length) and beta-sheet-oleate (41 amino acids in length) were not evaluated in this study. The 5 amino acid peptide length is the minimal number that mass spectrometry can detect and is the shortest peptide length for ACP prediction available (mACPred [>=5 amino acids], Anti-CP2.0 [4-50 amino acids], and ACPred-FL [10-50 amino acids]). However, the shortest peptide in the protein data bank is seven amino acids long as this size is needed to form the crystalline structure of the alpha-helical peptide. A peptide length of 25 amino acids or greater may suffer from peptide aggregation and poor solubility. Moreover, the lengths of peptides containing 13-24 amino acid residues were effectively similar in cell uptake. Thus, 25 amino acids length fulfilled this requirement. The mechanism of ALA-A2 is as a cell penetrating peptide with the ability to induce autophagy-mediated cancer cell death. ALA-A2 passes through the plasma membrane to the intracellular compartment of A549 lung cancer cells , and disturbs cancer cell homeostasis. ALA-A2-treated A549 cells exhibit downregulation of chaperone proteins involved in autophagic processes, including heat shock 70 kDa protein 8 (HSPA8), heat shock protein HSP90 alpha (HSP90AA1), and beta (HSP90AB1) . Although the exact intracellular targets of ALA-A2 have yet to be determined, the mode of anticancer actions of ALA-A2 has shared with previous studies. Ding et al.[ 21a ] showed that the engineered peptide Trx-pHLIP-Beclin1 could induce autophagic cell death in SKOV3 ovarian cancer cells. Pelaz et al.[ 21b ] reported that a designed peptide, TAT-Cx43266-283, deregulated autophagy and induced glioblastoma stem cell death. Recently, Dent et al. reported that the formation of autophagosomes was induced in HCT116 colon cancer following the inhibition of ATPase activities of HSP90 and HSP70. Thus, ACP-induced autophagy cancer cell death is probably explained, at least in part, by disturbing the expression and function of heat shock proteins. This is consistent with a report by Zhao et al.,[ 21c ] in which a novel HSP90 inhibitor, DPB, could inhibit A549 lung cancer growth via inducing apoptosis and autophagy. HSP90 is known as the cancer chaperone which plays a crucial role in maintaining the stability of oncogenic drivers in lung adenocarcinoma. Suppression of HSP90 leads to the degradation of oncogenic drivers and a loss of lung cancer cell viability. Overexpression of HSP90 has been correlated with a poorer prognosis and chemoresistance in patients with non-small-cell lung carcinoma. The findings reported herein support ALA-A2 inducing autophagy through downregulation of HSP90 expression in lung adenocarcinoma . Future studies on the molecular interaction between ALA-A2 and HSP90 would be promising. Ultimately, ALA-A2 peptide could be tested as an adjuvant therapy to attenuate chemoresistance in non-small-cell lung carcinoma. 4 Conclusion This study describes a novel strategy for searching for new ACPs. To validate this strategy, ALA-A2 was discovered to be a new ACP by integrating the computational peptide library of alpha-lactalbumin with downstream in silico ACP screening and in vitro experimental validation. ALA-A2 specifically inhibited lung adenocarcinoma cells through autophagy induction and cancer cell death. This approach, when applied to an expanded computational peptide library based on a large number of proteins, has great potential to minimize the time and cost of therapeutic peptide research. 5 Experimental Section Cell Culture All cell lines were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA). The A549 lung adenocarcinoma (ATCC CCL-185TM), MDA-MB-231 triple-negative breast adenocarcinoma (ATCC HTB-26TM), and SH-SY5Y neuroblastoma (ATCC CRL-2266TM) cell lines were cultured in Dulbecco's Modified Eagle's Medium (DMEM)-high glucose (Gibco, Thermo Fisher Scientific, MA, USA). HT29 colon adenocarcinoma (ATCC HTB-38) cell lines were maintained in DMEM/Nutrient Mixture F-12 (Gibco). K562 chronic myeloid leukemia (ATCC CRL-3344) were grown in Roswell Park Memorial Institute Medium 1640 (Gibco). The cells were cultured in medium supplemented with 10% fetal bovine serum (Gibco) and 1x penicillin/streptomycin (Gibco) and incubated in a 5% CO2 incubator with saturated humidity. Computational Generation of Alpha-Lactalbumin-Inspired Peptide Library The amino acid sequence of human alpha-lactalbumin retrieved from UniProt ID P00709 (last accessed on 14 September 2020) served as the template for generating the in silico peptide library. A peptide generator, ALA2Peptide, was coded to generate all possible peptides of alpha-lactalbumin ranging in the optimal length of ACP (5-25 amino acids) with stepping 1 amino acid each (from N-terminal to C-terminal). This program can be accessed via The output peptide library containing 2688 distinct peptide sequences is provided in Table S1, Supporting Information. In Silico ACP Screening The in silico ACP screening was performed as described with a minor modification. Three different ML models: mACPpred (a support vector machine-based predictor; ), ACPred-FL (a sequence-based predictor; ), and AntiCP2.0 (an ensemble tree classifier-based predictor; ), were used to predict physicochemical and anticancer properties. The geometric mean of ACP probabilities was calculated from the three ML models to serve as the consensus score as well as net charge prediction. The PEP-FOLD3 de novo peptide structure prediction webserver was used to predict the secondary structure of the peptides with >=3 positive charges (25 out of 2688). Top-ranked peptide candidates (ALA-A1, ALA-A2) were defined as the top ranked peptides by the consensus score with non-redundant sequence, having >=3 positive charges, and containing alpha-helical secondary structure. ALA-A3 and ALA-A4, the lower-ranked positively charged peptides with redundant sequence to ALA-A1 and ALA-A2, were included as comparators. BMP-S6, a known bovine milk-derived ACP, served as the positive ACP control, while the untreated condition was the blank (negative) control of this experiment. Synthetic Peptides Five synthetic peptides (purity >98%) were custom-made by GL Biochem (GL Biochem [Shanghai] Ltd., Shanghai, China). These peptides included ALA-A1, NH2-RFFVPLFLVGILFPAILAKQFTK-COOH; ALA-A2, NH2-KLWCKSSQVPQSR-COOH; ALA-A3, NH2-RFFVPLFLVGILFPAILAKQFTKC-COOH; ALA-A4, NH2-LFQISNKLWCKSSQVPQSRN-COOH; and BMP-S6 (the positive control), NH2-FKCRRWQWRMKKLGAPSITCVR-COOH. The peptides were resuspended in fresh media to the final concentration before use. In Vitro Cancer Cytotoxicity Screening The protocol previously described by Chiangjong et al. and Baindara et al. was modified for use in determining the cytotoxicity of peptides on the various cancer types. Adherent cells were seeded at 1 x 104 cells/well into a 96-well plate 24 h prior to replacing the media containing the peptide of interest. Suspended cells were seeded at 1 x 104 cells/well in the media containing the peptide of interest. Five human cell lines, including lung cancer (A549), colon cancer (HT29), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and leukemia (K562) cells, were treated with the culture media containing the peptides at 200 mm for 24 h. Cell viability was then determined using Cell Proliferation Kit I, MTT (Roche Diagnostics GmbH, Mannheim, Germany): MTT labeling reagent (10 mL) was added to each well and incubated at 37 degC in a 5% CO2 atmosphere for 4 h. After incubation, 100 mL solubilizing solution was added to each well and incubated at 37 degC in 5% CO2 overnight. The absorbance at 570 nm (A 570) was measured for each well. The percentage of cell viability was calculated as: (1) % Cell Viability=[A570 of treated cells - A570 of mediaA570 of untreated cells-A570 of media] x 100 To evaluate dose-dependency, 1 x 104 cells/well were cultured in media containing ALA-A2 at 0, 6.25, 12.5, 25, 50, 100, 200, and 400 mm in a 96-well plate for 24 h. Cell viability was determined by the MTT assay, as above. Ex Vivo Hemolysis Assay The hemolysis assay was as described previously. After informed consent, peripheral blood (3 mL) was collected from three healthy individuals into heparin tubes (BD Biosciences, NJ, USA). The specimen was centrifuged at 2000 x g for 5 min at room temperature, and the plasma was discarded. The RBCs were washed twice with PBS and then resuspended in 0.9% normal saline solution at a volume equivalent to that of the original plasma. Approximately 0.8% v/v RBC suspension was incubated with the peptides at 200 mm (100 mL final volume) in a U-bottom 96-well plate at room temperature for 1 h with agitation. 1% v/v Triton X-100 was applied as a positive control. The untreated condition served as the blank control. After 1 h incubation, the supernatants were collected by centrifuging at 2000 x g for 5 min at room temperature. The absorbance of hemoglobin in the supernatant was measured at 415 nm. The hemolysis percentage was calculated as follows: (2) % Hemolysis = [sample absorbance-blank controlpositive control-blank control] x 100 This study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Human Research Ethics Committee, Faculty of Medicine Ramathibodi Hospital, Mahidol University (Protocol ID: MURA2020/759; with approval of amendment on May 5, 2021). Confocal Microscopy In 6-well plates containing a glass cover slip, A549 lung adenocarcinoma and HT29 colon adenocarcinoma cells were seeded at 2 x 105 cells/2 mL medium/well and incubated for 24 h. The medium was replaced with fresh medium with or without 200 mm FITC-tagged ALA-A2 peptide and incubated at 37 degC in 5% CO2 for 24 h. All cells were then incubated with PI (1:2000) and Hoechst 33342 (1:5000) in the culture medium at 37 degC in 5% CO2 for 15 min. The cells were washed with PBS twice before being fixed with 4% paraformaldehyde (PFA) in PBS. The fixed cells were washed twice with PBS and mounted in 20% glycerol in PBS. After being fixed in PFA, the positive PI staining control cells were permeabilized with 0.5% v/v Triton X-100 for 10 min. Thereafter, the cells were stained with PI for 15 min at room temperature, washed with PBS, and then mounted with 20% glycerol in PBS. Internalization was visualized by confocal fluorescence microscopy (Nikon Instruments, Inc., Melville, NY, USA). SWATH-Proteomic and Bioinformatic Analysis Targeted label-free proteomic analysis using SWATH/DIA was performed as described previously to explore the potential mechanisms of ALA-A2-induced A549 lung adenocarcinoma cell death. In brief, A549 lung adenocarcinoma cells were seeded at a density of 1 x 105 cells/well in a 24-well plate. After overnight incubation, the media were changed with fresh media with or without 200 mm ALA-A2 and incubated at 37 degC in 5%CO2 for 24 h. The cells were washed twice with PBS before lysis with Laemmli lysis buffer (62.5 mm Tris-HCl, pH 6.8, 10% v/v glycerol, 2% w/v SDS, and 2.5% v/v beta-mercaptoethanol). Total protein was quantified using the Bradford protein assay (Bio-Rad, Hercules, USA). 10 mg of protein was resolved by 12% SDS-PAGE before staining with Coomassie brilliant blue G-250, and the gel was cut into small pieces for in-gel tryptic digestion. An amount of peptide sample corresponding to 2.5 mg of total protein was resolved in an Eksigent nanoLC ultra nanoflow high performance liquid chromatography in tandem with a TripleTOF 6600+ mass spectrometer (ABSciex, Toronto, Canada) set for information-dependent acquisition (IDA) and DIA modes. The peptides were loaded onto a C18 column trap (Nano Trap RP-1, 3 mm 120 A, 10 mm x 0.075 mm; Phenomenex, CA, USA) at a flow rate of 3 mL min-1 of 0.1% formic acid in water for 10 min to desalt and concentrate the sample, which was then resolved by HPLC using a stationary phase of a C18 analytical column (bioZen Peptide Polar C18 nanocolumn, 75 mm x 15 cm, particle size 3 mm, 120 A; Phenomenex) with mobile phase gradients at a flow rate of 300 nL min-1 of 3-30% acetonitrile/0.1% formic acid for 60 min, 30-40% acetonitrile/0.1% formic acid for 10 min, 40-80% acetonitrile/0.1% formic acid for 2 min, 80% acetonitrile/0.1% formic acid for 6 min, 80-3% acetonitrile/0.1% formic acid for 2 min, and 3% acetonitrile/0.1% formic acid for 25 min. The eluate was ionized and sprayed into the mass spectrometer using OptiFlow Turbo V Source (Sciex). Ion source gas 1, ion source gas 2, and curtain gas were set at 19, 0, and 25 vendor arbitrary units, respectively. The interface heater temperature was 150 degC and ion spray voltage was 3.3 kV. Mass spectrometry was operated in the positive ion mode set for 3500 cycles per 105 min gradient elution. Each cycle performed one time of flight (TOF) scan (250 ms accumulation time, 350-1250 m/z window with a charge state of +2) followed by IDA of the 100 most intense ions, while the minimum MS signal was set to 150 counts. The MS/MS scan was operated in high sensitivity mode with 50 ms accumulation time and 50 ppm mass tolerance. Former MS/MS candidate ions were excluded for a period of 12 s after their first occurrence to reduce the redundancy of identified peptides. DIA mode was performed in a range of 350-1500 m/z using a predefined mass window of 7-m/z with an overlap of 1-m/z for 157 transmissible windows. MS scan was set at 2044 cycles, where each cycle performed one TOF-MS scan type (50 ms accumulation time across 100-1500 precursor mass range) acquired in every cycle for a total cycle time of 3.08 s. MS spectra of 100-1500 m/z were collected with an accumulation time of 96 ms per SWATH window width. Resolution for MS1 was 35 000 and SWATH-MS2 scan was 30 000. Rolling collision energy mode with collision energy spread of 15 eV was applied. The IDA and DIA data (.wiff) were recorded by Analyst-TF v.1.8 software (ABSciex). A total of 18 wiff files of IDA experiments (two groups; three biological replicates per group; three technical replicates per biological sample) were combined and searched using Protein Pilot v.5.0.2.0 software (ABSciex) against the Swiss-Prot database (UniProtKB 2022_01) Homo sapiens (20385 proteins in database) with the searching parameters as follows; alkylation on cysteine by iodoacetamide, trypsin enzymatic digestion, one missed cleavage allowed, monoisotopic mass, and 1% false discovery rate. The group file (Protein Pilot search result) was loaded into SWATH Acquisition MicroApp v.2.0.1.2133 in PeakView software v.2.2 (Sciex) to generate a spectral library. The maximum number of proteins was set as the number of proteins identified at 1% global FDR from fit. RT alignment was performed by the high abundance endogenous peptides covering the chromatographic range. SWATH data extraction of 18 DIA files (two groups; three biological replicates per group; three technical replicates per biological sample) was performed by SWATH Acquisition MicroApp (Sciex) using the following parameters; 5-min extraction window, 25 peptides/protein, 6 transitions/peptide, excluding shared peptides, peptide confidence >99%, FDR <1%, and XIC width of 20 ppm. SWATH extraction data, including the identities and quantities of peptides and proteins, was exported into an Excel file for further analysis. Comparative proteomic analysis was performed by using R program as described previously,[ 31b ] including log2 transformation, VSN normalization, missing value imputation by median, differential expression analysis, heatmap, and volcano plot at the thresholds of 2x fold change and p-value <0.05. The pathway enrichment analysis was analyzed by Reactome v.78 (last accessed on February 2, 2022) using the differential expressed proteins as the input, where a matched pathway with FDR <0.05 was considered statistically significant. Autophagy Activity Assay A549 cells (1 x 104 cells/well in a 96-well plate) were treated with 200 mm ALA-A2. Treated cells were maintained for 24 h before determining autophagy activity using an autophagy assay kit (ab139484, Abcam, Milpitas, CA). To prepare for the staining, the media was removed, and the cells were washed once with 1x assay buffer. The dual color detection solution was added to the wells and incubated for 30 min. The cells were washed and 1x assay buffer added to each well. The nuclear signal was excitation of 340 nm and emission of 480, whereas autophagosomes and autophagolysosomes were detected by excitation of 480 nm and emission of 530 nm. Autophagy activity was calculated by normalizing the autophagosome/autophagolysosome signal to the nuclear signal. Rapamycin (2 mm), a known autophagy inducer, was the positive control. This experiment was performed in three biological replicates. Statistical Analysis Data were presented as the number, percentage, or mean +- SD as appropriate. One-way ANOVA with Tukey's post hoc tests for multiple comparisons was performed. A p-value <0.05 was considered statistically significant. Ethical Approval Statement The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Human Research Ethics Committee, Faculty of Medicine Ramathibodi Hospital, Mahidol University (Protocol ID: MURA2020/759; with approval of amendment on May 5, 2021). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Conflict of Interest The authors declare no conflict of interest. Author Contributions T.L. and P.O.-y. contributed equally to this work. Conceptualization: So.C.; Methodology: T.L., P.O.-y., W.C., So.C.; Validation: W.C., So.C.; Formal analysis: T.L., P.O.-y., Se.C., W.S., W.C., So.C.; Investigation: T.L., P.O.-y., Se.C., W.S., W.C., So.C.; Resources: D.S.N., A.L.M., S.H., So.C.; Software: P.O.-y., So.C.; Writing--original draft preparation: T.L., P.O.-y.; Writing--review and editing: Se.C., W.S., D.S.N., A.L.M., S.H., W.C., So.C.; Visualization: T.L., P.O.-y., So.C.; Supervision: D.S.N., A.L.M., S.H., W.C., So.C.; Funding acquisition: So.C. All authors have read and agreed to the published version of the manuscript. Supporting information Supporting Information Click here for additional data file. Acknowledgements The authors thank Dr. Rakkreat Wikiniyadhanee for experimental discussion, and Kanthanadon Dittharot for technical assistance. P.O.-y. was supported by the Dean's Research Novice Award for her research activity. This research was funded by the New Discovery and Frontier Research Grant of Mahidol University, grant number NDFR19/2563. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Data Availability Statement The data that support the findings of this study are available in the supplementary material of this article. |
PMC10000270 | J Gen Fam Med J Gen Fam Med 10.1002/(ISSN)2189-7948 JGF2 Journal of General and Family Medicine 2189-6577 2189-7948 John Wiley and Sons Inc. Hoboken 10.1002/jgf2.603 JGF2603 JGF2-2022-0153.R1 Letter to the Editor Letters to the Editor Five strategies on writing research papers for beginners and young general medicine doctors Miyagami Taiju MD, PhD 1 [email protected] Ishizuka Kosuke MD, PhD 2 Harada Taku MD 3 Nagano Hiroyuki MD 4 Otsuka Yuki MD, PhD 5 Kumakawa Tomoko MD 6 Yamashita Shun MD, PhD 7 1 Department of General Medicine, Faculty of Medicine Juntendo University Tokyo Japan 2 Division of General Internal Medicine, Department of Internal Medicine St. Marianna University School of Medicine Kanagawa Japan 3 General Medicine Nerima Hikarigaoka Hospital Tokyo Japan 4 Department of Healthcare Economics and Quality Management, Graduate School of Medicine Kyoto University Kyoto Japan 5 Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan 6 School of Public Health University of California Berkeley California USA 7 Department of General Medicine Saga University Hospital Saga Japan * Correspondence Taiju Miyagami, Department of General Medicine, Juntendo University Faculty of Medicine, 2-1-1, Bunkyo-Ku, Tokyo, Japan. Email: [email protected] 18 1 2023 3 2023 24 2 10.1002/jgf2.v24.2 141142 15 12 2022 02 11 2022 25 12 2022 (c) 2023 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association. This is an open access article under the terms of the License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. We propose five important strategies for young generalists to write original research and papers. We hope that even beginners will understand and practice these five strategies, and help young generalist to write research papers based on clinical questions that arise in their daily practice. source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 pmc To the Editor: Japanese general medicine doctors (GMs) tend not to conduct research and place importance on it compared with clinical practice and education. 1 Tips for GMs to publish case reports emphasize the importance of clarifying the blueprint of the writing process in advance. 2 However, there are no reports on methods for publishing clinical research papers, except for case reports. We consider that for GMs to conduct research, strategies should be clarified, including those aspects which they share with specialists. Seven GMs (median years since graduation: 10 years), who have actively published original papers in international peer reviewed journals, completed interactive interviews and a narrative literature review about the likely stumbling blocks for beginners (who have never written a paper before) while writing their first online research paper. Hence, we propose five important strategies to help young GMs author original research papers. (Table 1). TABLE 1 Five strategies for becoming an academic generalist Strategy 1. Keeping the motivation. Strategy 2. Connecting clinical question to research question on a daily basis. Strategy 3. Reviewing previous research. Strategy 4. Conducting descriptive studies first. Strategy 5. Assigning a mentor and forming a project team. STRATEGY 1: KEEPING THE MOTIVATION First, being motivated in any situation and challenging daily practice makes the emergence of a clinical question more likely. The joy we experience when our products are published and by knowing that having a research perspective improves our clinical skills is motivation in itself. We encourage GMs who have not yet taken the plunge to take the first step. STRATEGY 2: CONNECTING CLINICAL QUESTIONS TO RESEARCH QUESTIONS ON A DAILY BASIS To conduct research, it is crucial to link clinical questions--questions that occur in the clinical setting--to research issues by considering their ethics, novelty, and viability. Eventually, we may be able to form GMs' original research team. STRATEGY 3: REVIEWING PREVIOUS RESEARCH We regret not conducting a thorough review of previous studies during the planning stage, either due to a lack of research items after beginning research or to previously published reports on the subject. Conducting a generic, yet comprehensive search of previous studies and setting survey items and inclusion criteria are critical. STRATEGY 4: CONDUCTING DESCRIPTIVE STUDIES FIRST This strategy is particularly important among these five strategies. Descriptive studies are able to summarize study data efficiently and logically, without a control group, intervention, or complex statistical calculations. 3 Investigating epidemiological frequencies enables answering questions in clinical practice. In addition, GMs have a high affinity for descriptive research because they have conducted several studies on diagnosis and epidemiology. 4 In our experience, we recommend that beginners start with descriptive studies. STRATEGY 5: ASSIGNING A MENTOR AND FORMING A PROJECT TEAM Hospitalists in the U.S. report that the lack of a mentor interferes with their research work. 5 Therefore, finding a mentor to discuss team building in detail and determining the division of roles between the mentor and the team are crucial. Mentors may not be easily available at GMs' own institutions; thus, it is important to find one at academic conferences or social network services and actively seek advice. We hope that these five strategies will help beginners and young GMs author research papers. AUTHOR CONTRIBUTIONS All authors had access to the data and a role in writing the manuscript. CONFLICT OF INTEREST None. REFERENCES 1 Miyagami T , Yamada T , Kanzawa Y , Kosugi S , Nagasaki K , Nagano H , et al. Large-scale observational study on the current status and challenges of general medicine in Japan: job description and required skills. Int J Gen Med. 2022;15 :975-84.35125887 2 Shikino K , Watari T , Tago M , Sasaki Y , Takahashi H , Shimizu T . Five tips on writing case reports for Japanese generalists. J Gen Fam Med. 2020;22 :111-2.33717791 3 Vetter TR . Descriptive statistics: reporting the answers to the 5 basic questions of who, what, why, when, where, and a sixth, so what? Anesth Analg. 2017;125 :1797-802.28891910 4 Tago M , Hirata R , Watari T , Shikino K , Sasaki Y , Takahashi H , et al. Future research in general medicine has diverse topics and is highly promising: opinions based on a questionnaire survey. Int J Gen Med. 2022;15 :6381-6.35942291 5 Dugani SB , Geyer HL , Maniaci MJ , Burton MC . Perception of barriers to research among internal medicine physician hospitalists by career stage. Hosp Pract. 1995;2020 (48 ):206-12. |
PMC10000271 | We report a case of spontaneous remission of hepatocellular carcinoma in an 84-year-old woman who was managed in our best supportive care clinic. The tumor, once relapsed regardless of the application of conventional transcatheter arterial chemoembolization and radiofrequency ablation, regressed spontaneously within 4 months. The presence of an occlusive thrombus in the portal vein feeding to the site of the tumor suggests that the reduced blood supply might have caused tumor necrosis. Furthermore, the successful eradication of hepatitis C virus maintained performance status, and good nutrition might play other roles on it. We report a case of spontaneous remission of hepatocellular carcinoma in an 84-year-old woman who was managed in our best supportive care clinic. hepatocellular carcinoma palliative care spontaneous regression source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Yamamoto N , Yamamoto C , Tajitsu T . Spontaneous regression of hepatocellular carcinoma in a pure palliative care setting. J Gen Fam Med. 2023;24 :126-128. 10.1002/jgf2.588 pmc1 INTRODUCTION Spontaneous regression of hepatocellular carcinoma (HCC) is very rare. 1 It is estimated to occur in 1 in 140,000 cases worldwide. 1 By 2019, only 106 cases were reported in the English written literature. 1 We report a case of spontaneous regression of HCC in a woman with liver cirrhosis caused by hepatitis C virus (HCV) infection. The patient agreed to the publication of her case by providing informed consent. The project was approved by an institutional ethics committee. For human subjects, the investigation was conducted in accordance with the Declaration of Helsinki of 1975. 2 CASE PRESENTATION An 84-year-old native Japanese woman presented to our clinic for the best supportive care (BSC) of HCC. She had been diagnosed with HCV-related liver cirrhosis since 2008. A tumor 30 mm in diameter in segment 3 (S3) and a tumor in 10 mm in diameter in S8 developed as a complication of liver cirrhosis in 2017. She initially refused treatment, but she was treated with conventional transcatheter arterial chemoembolization (c-TACE) of the tumor in S3 using a gelatin sponge and lipiodol combined with 20 mg of epirubicin on November 26, 2019. Subsequent c-TACE of tumor in S8 was abandoned due to the patient's distress during the procedure. It was treated with radiofrequency ablation (RFA) on April 3, 2020. Ledipasvir 90 mg and sofosbuvir 400 mg were administered for 12 weeks in parallel with the tumor treatment resulting in the eradication of her HCV infection. Her serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) dropped once following the RFA, but they rose again persistently , and on June 29, 2020, a recurrent tumor with a diameter of about 30 mm was found in S8, accompanied with an occlusive portal vein thrombus in P8 again . She was referred to our clinic on July 29, 2020, because she refused any more active anti-tumor treatment. At the initial presentation, her Karnofsky Performance Status remained at 90. Laboratory examination showed serum albumin of 4.1 g/dL and total lymphocyte counts of 1615/mm3. On the contrary, serum AFP value had declined to 5261.8 ng/mL from 16962.3 ng/mL in 3 months. It continued to decline to 12 ng/mL 2 months later . When her PIVKA-II was measured using the stored serum, it was found to have decreased simultaneously . Persistent eradication of HCV was confirmed using real-time polymerase chain reaction. Contrast enhancement triple-phase computed tomography was performed to confirm the spontaneous remission of her HCC. The previously affected area of S8 enhanced in the arterial phase with an early washout pattern in the portal phase was almost disappeared in the present computed tomography (CT). In addition, the portal occlusion on P8 had resolved . Giving the information about the spontaneous regression definitely pleased her and her caregivers. Her serum values of AFP and PIVKA-II are gradually rising, but they remained still low over a further 1 year of follow-up (AFP, 26.3 ng/mL; PIVKA-II, 24 mAU/mL on December 13, 2021) . Throughout the entire time in the care of our BSC practice, she received neither curative treatment for cancer nor any specific treatment for symptoms due to the absence of discomfort. FIGURE 1 The patient's serum alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels show a marked decline after discontinuing anti-cancer therapy. FIGURE 2 Axial image of contrast-enhanced computed tomography shows a hypodense tumor with a diameter of about 3 cm in S8 (white arrow) (A) accompanied by portal vein thrombosis in P8 (black allow) (B) before regression in June 2020 and markedly decreased in size with the resolution of the portal vein thrombosis after regression in September 2020 (C, D). 3 DISCUSSION The patient's clinical course is compatible with the definition of "spontaneous regression of cancer." 2 Tumor regression may be a delayed effect of RFA, but it is inconsistent with persistent elevation of tumor markers and CT findings for 2 months after RFA. Several hypotheses have been advocated to explain the mechanism of the spontaneous regression of HCC, but it has not been confirmed yet. 1 Diminished blood supply by the thrombus in the portal vein should have caused our patient's tumor to become necrotic as previously reported. 1 Six of the 24 spontaneous regression of HCC cases had impaired blood flow in the portal vein. 3 Besides, one case of complete histopathological necrosis after preoperative portal vein embolization was reported. 4 Recently, advances in molecular biology have led to the development of angiogenesis inhibitors that block the blood flow that cancer cells need to grow. 5 Sorafenib, one of the angiogenesis inhibitors, has been used currently as a standard regimen for advanced HCC in Japan. 5 Additionally, the successful eradication of persistent hepatitis viral infection which accelerates the carcinogenic process, maintenance of Karnofsky Performance Status, and good nutrition may have played other roles. 6 With the accumulation of similar cases and integration of knowledge, we can expect to establish new treatment strategies for HCC. 1 , 3 A major limitation of this report is that we diagnosed the tumor as HCC based on laboratory data and imaging features 7 without histopathological confirmation. However, it is well-known that HCV infection is a major cause of cirrhosis, significantly increasing the risk of HCC. 8 Given that similar cases have been reported previously, 1 , 9 we consider the clinical evidence to be sufficient. In our case, further close follow-up is required, as there have been some evidences that show once spontaneously regressed HCC cases recurred and resulted in death after few years. 1 , 6 We encountered spontaneous regression of HCC in the clinical setting of BSC. Spontaneous regression of cancer is a recognized verifiable phenomenon, even though it is quite rare. 2 When caring for patients with advanced cancer, we must be more careful, not just obsessed with conventional concepts. AUTHOR CONTRIBUTIONS All authors meet the ICMJE criteria for authorship. ETHICAL APPROVAL None. PATIENT CONSENT The patient has provided free written informed consent for the publication of this manuscript. CLINICAL TRIAL REGISTRATION None. INFORMED CONSENT The patient provided written informed consent. CONFLICT OF INTEREST The authors declare no conflicts of interest for this article. PERMISSION TO PUBLISH The patient has provided consent for the publication of this report. ACKNOWLEDGMENTS We thank Dr. Sadayoshi Ohubu, Dr. Satoshi Monno, Dr. Yukou Ikezawa, Dr. Mari Katsuno, and Dr. Sho Komada for their kind advice. |
PMC10000272 | Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature. Exome data for 109 individuals with interstitial cystitis/bladder pain syndrome is analyzed for Mendelian disorders. Two genes identified within the cohort, ATP2C1 and ATP2A2, are associated with dermatological phenotypes. Further evaluation with larger numbers is needed, though genetically screening individuals with IC/BPS may be useful in diagnosing and treating this painful disorder due to its heterogeneous nature. bladder genetics genital genomics Mendelian pain urinary NIH 10.13039/100000002 5U54DK104309-07 Centers for Disease Control and Prevention 10.13039/100000030 CDC 1U01DP006634-01-00 Boston Children's Hospital Intellectual and Developmental Disabilities Research Center Molecular Genetics Core FacilityP50HD105351 Eunice Kennedy Shriver National Institute of Child Health and Human Development 10.13039/100009633 NIH/NIMH U01 MH119690 Broad Institute and Boston Children's Collaborative Grant Award source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 E. Estrella , S. Rockowitz , M. Thorne , P. Smith , J. Petit , V. Zehnder , R. N. Yu , S. Bauer , C. Berde , P. B. Agrawal , A. H. Beggs , A. G. Gharavi , L. Kunkel , C. A. Brownstein , Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort. Advanced Genetics 2023, 4 , 2200013. 10.1002/ggn2.202200013 pmc1 Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Prevalence estimates in the past decade now exceed 10 million in the United States (3-7% of women and 2-4% of men). Symptoms of IC/BPS are often debilitating and can affect work, family, interpersonal relationships, sleep, and sexual activity. Understanding the etiology and pathogenesis of interstitial cystitis is paramount to the development of targeted therapies against this debilitating condition. The average time from presentation to the general practitioner to specialty clinic referral and subsequent diagnosis ranges from 3 to 7 years. The diagnosis of IC/BPS is associated with high costs; while IC/BPS accounted for only 0.1% of all medical treatment and prescription drug claims in 2002 in the United States. That year the mean annual medical cost for individuals diagnosed with IC/BPS was $8420, compared to a mean of $4169 for those without IC/BPS. Recent studies of kidney and urologic disorders have shown that many individuals have genetic diseases that remain undiagnosed after standard clinical evaluation. For example, 5-8% of individuals with developmental disorders of the urinary tract have an undetected genomic disorder. We also have seen reports of increased incidence of IC/BPS in first degree relatives of people diagnosed with IC/BPS. Together this data point to a genetic etiology for IC/BPS. Our hypothesis was that some individuals with IC/BPS had undiagnosed Mendelian conditions, and that the genes behind these Mendelian conditions could be informative candidate genes leading us to an IC/BPS gene or gene pathway and ultimately an etiology. Therefore, we screened biological samples and phenotypic information on 109 unrelated individuals with severe IC/BPS. To test for Mendelian causes of IC/BPS, a diagnostic variant analysis of exome sequencing (ES) data was performed. To test whether the candidate genes identified in the Mendelian analysis had increased rare variant burden, we used the Genomic Learning System at Boston Children's Hospital (Boston, MA) to perform sequence kernel association test (SKAT) analysis implemented in the Genuity Science Sequence Miner platform (Cambridge, MA). 2 Experimental Section 2.1 Phenotyping and Diagnosis of Cases 238 individuals with IC/BPS were identified by collaborating physician referral or self-referral from ads placed on Clinicaltrials.gov, the Interstitial Cystitis Association (ICA) website and newsletters, and Interstitial Cystitis Network (ICN). Inclusion criteria were 1) Diagnosed with IC/BPS by a clinician 2) Symptoms of urinary urgency and pelvic, suprapubic and/or abdominal pain for 3 months or longer in a 6 month period. Exclusion criteria were 1) evidence of bacterial urinary tract infections in last 3 months, 2) structural urinary tract abnormalities, and 3) bladder, prostate, cervical or uterine cancer. Probands included both adults and children with an IC/BPS diagnosis. All individuals were enrolled in the research program following informed consent under an IRB-approved protocol at Boston Children's Hospital (04-11-160). Each proband with a clinical diagnosis of IC/BPS in the cohort has had the following clinical workup: cystoscopy with hydrodistension (i.e., looking for glomerulations, Hunner's ulcers, and cancer), a physical exam that ruled out structural defects and infection via urinalysis, and a voiding analysis to assess for muscle dysfunction (e.g., detrusor or pelvic floor). Participants have also completed several questionnaires including the O' for women, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) for men, and a diagnostic questionnaire that asks about symptoms and co-morbidities common in IC/BPS. Before enrollment, all data were reviewed by the study urologist to confirm the IC/BPS diagnosis. After enrollment, a 3-4 generation pedigree focusing on urinary and pain symptoms was obtained. Additional family members were enrolled using a tiered priority system. Families were stratified based on factors like presence of Hunner's ulcers (tier 1, N = 10 families), multiple family members with IC/BPS diagnosis (tier 2, N = 45 families), multiple family members with IC/BPS symptoms (tier 3, N = 60 families), and sporadic cases and family members (tier 4, N = 123 individuals and families). A review of the inheritance pattern in this cohort revealed an autosomal dominant inheritance pattern with variable expressivity in more than 50% of enrolled families. In total, 415 individuals were enrolled. 177 additional family members from 135 families were recruited, including 121 family members with a diagnosis of IC/BPS and 56 without a diagnosis of IC/BPS. 103 individuals did not have any relative enroll. 2.2 Exome and Mendelian Analyses Saliva samples were collected and white blood and buccal epithelial cell DNA were extracted using Oragene kits (DNA Genotek). The highest quality DNA for the cohort was sent for ES; 109 affected individuals (probands or an affected family member) from 109 distinct families were selected. Tiers, age of onset, and questionnaire scores were not taken into account as all individuals had a diagnosis of IC/BPS. Illumina-based short read whole ES was conducted at the Broad Institute (Cambridge, MA) as previously described. After ES, all variants were annotated based on their predicted effect on protein function using the Codified Genomics platform (San Diego, CA). A filter on MAF of 0.005 for autosomal dominant and 0.01 for autosomal recessive variants, was chosen as a reasonable maximum allele frequency for disease-causing variants. Allelic frequencies were estimated based on public databases including gnomAD, dbSNP, and the 1000 Genomes Project, as well as 2672 internal control sequences (healthy parents of individuals with suspected Mendelian disorders). Prediction of pathogenicity was computed using algorithms including PolyPhen. Additional resources for facilitating variant interpretation and establishing genetic causality included the Human Gene Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM), and an in-house curated list of genes and pathways with a known or postulated association to IC/BPS, pain, bladder, kidney, urogenital, immunological, skin and developmental disorders. Both pleiotropic and non-pleiotropic genes were included as candidates. Next, the potentially disease-causing variants in each individual were assessed using automated ACMG criteria scoring in Varsome (varsome.com) and manually reviewed for accuracy of clinical interpretation. Finally, Variants that were classified as "Variants of Uncertain Significance (VUS)," "Likely Pathogenic," and "Pathogenic" were manually queried for ACMG classification and for presence in ClinVar. All individuals were also called with the Genome Analysis Toolkit following the best practice workflow as described in Rockowitz et al. and resulting VCF data analyzed in the Genuity Science (Reykjavik, Iceland). Within Genuity, ES data were analyzed for potentially disease causing variants in each proband. Again, a filter on MAF of 0.005 for autosomal dominant and 0.01 for autosomal recessive variants was used. Variant Effect Prediction (VEP) high/moderate (i.e., transcript ablation, splice acceptor variant, splice donor variant, stop gained, frameshift variant, stop lost, start lost, transcript amplification, inframe insertion, inframe deletion, missense variant, protein altering variant, splice region variant, or incomplete terminal codon variant) were considered. Genuity automatically screens for presence in ClinVar, HGMD, and OMIM. 2.3 Statistical Analysis SKAT is a supervised, flexible, computationally efficient regression method to test for association between genetic variants (common and rare) in a region and a continuous or dichotomous trait while adjusting for covariates. The authors were interested to learn about the gene burden for the genes identified as variants of uncertain significance, pathogenic, or likely pathogenic by the Mendelian analysis/Varsome pipeline described above. 2.3.1 Preprocessing of Data 109 individuals (93 female and 16 male) with IC/BPS were loaded as cases for the SKAT analysis. Cases with diagnostic variants were removed (6 individuals removed), along with ES with poor coverage, abnormal average SNV reference fraction, or yield below 0.80 (17 individuals removed). The yield field indicates the proportion of the overall variants that can be assigned to either homozygous reference or heterozygous call. If a mix of ES and WGS or different capture kits was used, the ES samples will show a very low yield as coverage was missing in areas. After filtering, 86 affected individuals remained (80 female, 6 male). Controls consisted of 90 unrelated healthy individuals (80 females, 10 males), who were unaffected parents of patients with suspected Mendelian disorders unrelated to IC/BPS. Controls were 100% Caucasian (self-reported), matching the 100% Caucasian background of this subset of the IC/BPS cohort. 2.3.2 Gene Selection Five genes were selected based on the results of the Mendelian analysis. Two genes were ATPase calcium-transporters with pathogenic rare or private variants identified in the cohort: ATP2C1 and ATP2A2. Three additional genes, SIX5, ENAM, and DCAF8, were included due to previously reported pathogenic variants identified in the cohort and expression occurring in the urogenital tissues. 2.3.3 Statistical Methods SKAT analysis was performed in Genuity Science (version 2.0.1). VEP high/moderate variants were used for analysis. Allele frequency upper threshold was 0.01, with a Harvey-Weinberg equilibrium threshold of 1e-6. Bonferroni correction was applied for five genes tested and a p-value less than 0.01 was considered to indicate significant difference. Though cases and controls were matched on sequencing platform, sequencing facility, and ancestry, five sets of housekeeping genes were also used as controls to ensure there were no batch effects creating systematic differences between case and control sequences (e.g., increased rare variant calls in IC/BPS cohort). The five sets of five housekeeping genes were selected by a pseudorandom number generator from a list of 3803 housekeeping genes from Eisenberg et al. (see Table S1, Supporting Information for housekeeping gene list). 3 Results 3.1 Demographics 109 unrelated individuals (93 women 16 men) underwent ES. 100% of individuals were Caucasian/White and non-Hispanic ancestry (self-reported). Average age and selected descriptive characteristics are stated in Table 1 . No children under 18 were sequenced. Table 1 Selected characteristics for the IC/BPS individuals who underwent ES Gender N Min Max Mean Std Dev Male Years between first symptom and diagnosis 16 0 29 7 9 Age (years) IC symptoms began 16 0 74 31 17 Age IC was diagnosed 16 8 74 38 17 Current age 54 24 77 51 14 Female Years between first symptom and diagnosis 93 0 59 8 10 Age (years) IC symptoms began 93 2 74 32 16 Age IC was diagnosed 93 5 75 40 14 Current age 54 24 81 51 18 John Wiley & Sons, Ltd. 3.2 Mendelian Analysis We identified multiple candidate genes with variants of interest across the IC/BPS cohort. Two private heterozygous variants were identified in the ATPase calcium-transporting type 2C member 1 gene (ATP2C1) (ENST00000393221.4:c.2358A>T, p.Glu786Asp, (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (Likely Pathogenic). (Table 2 ). These variants were identified in two IC/BPS cohort probands (SF368-II-2-P2 & SF380-II-1-P2). The variant in SF380 was confirmed in CLIA certified genetic testing laboratory. The variant in SF368 is in process of CLIA confirmation. Pathogenic variants in ATP2C1 are causative for autosomal dominant Hailey-Hailey disease (OMIM # 169600), a blistering skin disorder. Table 2 Rare and predicted damaging variants in ATP2C1, ATP2A2, and SIX5 in IC/BPS Gene Associated condition Location Change Number affected, number of families ACMG categorization of variant ClinVar classification (Number entries for each classification, accessed Dec 30, 2021) ATP2C1 Hailey-Hailey chr3:130716462 ENST00000393221.4: c.2358A>T, p.Glu786Asp, 1,1 VUS/likely pathogenic PM2, PP2, PP3 supporting N/A ATP2C1 Hailey-Hailey chr3:130678173 ENST00000393221.4: c.989C>G, p.Thr330Ser 2,1 Likely Pathogenic PM2 Strong, PP2, PP3 Supporting N/A ATP2A2 Darier-White chr12:110729840 ENST00000539276.2: c.235G>A, p.Glu79Lys 4,2 Likely Pathogenic PM2 Strong, PP2, PP3 Supporting N/A SIX5 Branchiootorenal syndrome 2 (BOR2) chr19:46271631 ENST00000317578.6: c.472G>A, p.Ala158Thr 1,1 VUS/likely pathogenic PP5 Strong, PP3 Supporting VUS (1), Pathogenic (2) John Wiley & Sons, Ltd. A VUS/Likely Pathogenic variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) was identified in two probands from the IC/BPS cohort, SF138-III-1-P2, and SF355-III-1-P2. This variant is not identified in gnomAD (accessed September 1, 2022), indicating that the variant is rare or private. This variant is also conserved across 46 vertebrate species. CLIA confirmation is ongoing in these participants and affected family members . The ATP2A2 gene has been shown to cause Darier-White disease (OMIM # 124200), another autosomal dominant dermatological disorder. Interestingly, all affected individuals reported skin findings of psoriasis and/or eczema as a comorbidity to their IC/BPS disease. Figure 1 Pedigrees for SIX5 and ATP2A2 families. We also identified a family with a heterozygous variant in the SIX5 (ENST00000317578.6:c.472G>A, p.Ala158Thr) . This variant is previously reported as likely pathogenic, indicating a possible diagnosis of Branchiootorenal syndrome 2 (BOR2, OMIM # 610896). While the variant carriers do not have documented uro-genital malformations, as they were exclusionary criteria for our study, it is possible that the individuals have subtle urogenital anomalies that eluded detection. Interestingly, one family member was excluded due to a urogenital malformation. She was subsequently enrolled in this study and was confirmed to also harbor the heterozygous SIX5 variant. We feel this family has a likely diagnosis of BOR2 syndrome with variable expressivity. This variant is in the process of being CLIA confirmed and reported back to family members for further investigation. A previously reported heterozygous variant in the DCAF8 gene was identified in an individual (ENST00000368073.3:c.949C>T, p.Arg317Cys). DCAF8 has been implicated in autosomal dominant Giant axonal neuropathy type 2 (OMIM # 610100). While giant axonal neuropathy type 1 is associated with a neurogenic bladder phenotype, the DCAF8-associated type 2 phenotype is associated with distal sensory impairment, lower extremity muscle weakness, and atrophy after the second decade, but does not reference neurogenic bladder. One individual had a previously reported heterozygous variant in the ENAM gene, (ENST00000396073.3: c.1259_1260insAG, p.Pro422ValfsTer27), associated with Amelogenesis imperfecta (AI) - hypoplastic autosomal dominant. AI usually occurs alone but has been reported in association with multiorgan syndromes such as nephrocalcinosis, hypothalamo-hypophyseal insufficiency, and Kohlschutter Syndrome. Rarely, AI has been associated with distal renal tubular acidosis, characterized by hypokalemia, systemic acidosis, and polyuria. The SEC63 variant seen in an affected individual (ENST00000369002.4:c.1605dupA, p.Pro536ThrfsTer24) is associated with polycystic liver disease (PCLD). However, renal features are not common in PCLD and any relationship of SEC63 to the IC/BPS phenotype in this individual is unclear. Additional variants in genes with known expression in urogenital tissues and previously reported pathogenic variant interpretations are listed in Table 3 , with single heterozygous variants in autosomal recessive conditions reported in Table 4 . Individuals with rare variants in the IC/BPS candidate gene frizzled class receptor 8 (FZD8) are reported in Table 5 . Table 3 Autosomal dominant Mendelian disorder-associated variants in 109 individuals with IC/BPS Gene Condition Location Change dbsnp Number affected, number of families ACMG classification ClinVar classification (Number entries for each classification, accessed Dec 30, 2021) DCAF8 Axonal hereditary motor and sensory neuropathy (HMSN2) with infrequent giant axons chr1:160206935 ENST00000368073.3: c.949C>T, p.Arg317Cys rs587777425 1;1 VUS/likely pathogenic PP5 Moderate, PM2, PP3 Supporting Pathogenic (1) ENAM Amelogenesis imperfecta - hypoplastic autosomal dominant - local chr4:71508403 ENST00000396073.3: c.1259_1260insAG, p.Pro422ValfsTer27) rs587776588 1;1 Pathogenic PVS1 Very Strong, PM2 Moderate, PP5 Supporting Pathogenic (3), Likely Pathogenic (1) SEC63 Polycystic Liver Disease chr6:108214755 ENST00000369002.4: c.1605dupA, p.Pro536ThrfsTer24 rs752868449 1;1 Pathogenic PVS1 Very Strong, PP3, PP5 Supporting Pathogenic (1) John Wiley & Sons, Ltd. Table 4 Carrier status for autosomal recessive Mendelian disorders Gene Condition Location Change dbSNP Number affected; number of families ACMG classification ClinVar classification (Number entries for each classification, accessed Dec 30, 2021) WNK1 ]Neuropathy, Hereditary Sensory And Autonomic, Type IIa, Carrier chr12:977863 NM_001184985.2: c.2971C>T, p.Arg991Ter rs111033591 1;1 Pathogenic PVS1 Very Strong, PP5 Strong, PM2 Moderate, PP3 Supporting Pathogenic (1) GNE GNE Myopathy, carrier chr9:36218221 ENST00000372330.3: c.250G>T, p.Gly84Cys rs62541771 1;1 Pathogenic PP5 Very Strong, PM5 Moderate, PM1, PM2, PP3 Supporting Pathogenic (14) ATP7B Wilson Disease, carrier chr13:52524268 ENST00000242839.4: c.2605G>A, p.Gly869Arg rs191312027 6;5 Pathogenic PVS1 Very Strong, PM2 Strong, PP3 Supporting Pathogenic (7), Likely Pathogenic (5), VUS (3) John Wiley & Sons, Ltd. Table 5 FZD8 variants in the IC/BPS cohort Gene Condition Location Change dbSNP Number affected; number of families ACMG classification ClinVar classification (Number entries for each classification, accessed July 30, 2023) Allele frequency, gnomAD (accessed July 30, 2022) FZD8 Candidate, interstitial cystitis/bladder pain syndrome chr10:35929790 ENST00000374694.1:c.566_568delGGCinsAGT, p.Arg189_Pro190delinsLysSer 1;1 Variant of Uncertain Significance, PM2 Moderate, PP2 Supporting N/A 0 FZD8 Candidate, interstitial cystitis/bladder pain syndrome 10:35929561 ENST00000374694.1:c.797A>C, p.Asn266Thr 1;1 Variant of Uncertain Significance, PM2 Moderate, PP2 Supporting N/A John Wiley & Sons, Ltd. 3.3 Statistical Analysis Using SKAT, the five candidate genes from the Mendelian analysis with autosomal dominant or incomplete penetrance inheritance patterns (ATP2C1, ATP2A2, SIX5, ENAM, and DCAF8) were compared between cases (N = 86) and controls (N = 90). (Table S2, Supporting Information). ATP2C1 had a trend toward significance (p = 0.03, OR = 6.76) (Table 6 ), though after Bonferroni correction only a p-value of 0.01 would be considered significant. Six rare variants in ATP2C1 were identified in the IC/BPS cohort (see Tables S2 and S3, Supporting Information). One ATP2C1 variant was identified in the control cohort (NM_001199180.2):c.721A>G (p.Asn241Asp), scored as a VUS using ACMG criteria. No other candidate genes or housekeeping genes tested approached significance (see Tables S4 and S5, Supporting Information). Table 6 SKAT analysis of Mendelian disorder-associated genes returned to families and genes with plausible mechanisms of causing IC/BPS (86 cases and 90 controls). Markers and additional details are available in Tables S2 and S3, Supporting Information Gene Markers p-value (under 0.01 considered significant) OR ATP2A2 1 0.73 0.51 DCAF8 1 0.83 1.06 ENAM 6 0.19 3.34 SIX5 5 0.2 2.2 ATP2C1 6 0.03 6.76 John Wiley & Sons, Ltd. 4 Discussion The etiology of IC/BPS continues to remain elusive, However, first degree relatives of individuals with IC/BPS have an increased risk of also having an IC/BPS diagnosis. Recent studies of kidney and urologic disorders have also shown that many individuals have genetic diseases that are undiagnosed based on standard clinical evaluation. In particular, 5-8% of individuals with developmental disorders of the urinary tract have an undetected genomic disorder. Therefore, we hypothesized that a Mendelian disorder or a pathway of related disorders could be causative of symptoms diagnosed as IC/BPS. Our analysis utilized a Mendelian approach to analyze the ES data from 109 individuals with IC/BPS. This would allow us to both identify individuals with a potential mis-diagnosis of IC/BPS and work to identify an IC/BPS candidate gene or pathway of genes. In IC/BPS probands, we identified rare variants in two bladder-expressed genes in the ATP-family - ATP2A2 and ATP2C1. Pathogenic variants in these genes cause two related skin disorders called Darier-White and Hailey-Hailey disease, respectively. Individuals with these disorders present with vesicular or blistering skin lesions that can affect the genitourinary areas and cause pain (Table 7 ). The clinical follow-up of the affected individuals with ATP2A2 and ATP2C1 gene variants demonstrated that they all have skin findings consistent with Darier-White and Hailey-Hailey disease. These findings suggested that molecular defects that primarily manifest in skin and mucosal epithelial injury may also participate in the pathogenesis of urothelial defects and IC/BPS. Table 7 Comparative examination of the pathology and expression of genetic disorders caused by identified candidate genes (ATP2C1, ATP2A2, and SIX5 respectively) Symptoms Interstitial cystitis Hailey-Hailey (ATP2C1) Darier-White (ATP2A2) Branchiootorenal syndrome 2 (SIX5) Urgency, frequency (urination) X Pelvic/bladder pain X Skin lesions X X Vulval pain/lesions X X X Bladder/smooth muscle involvement X Abnormality of the nail X X Flare-ups of condition X X X Vesicoureteral reflux X X Causative gene expressed in bladder X X Causative gene expressed in genital tissue Endocervix epithelium, uterine tube epithelium John Wiley & Sons, Ltd. Darier-White Disease, an autosomal dominant disease caused by mutations in ATP2A2, is a keratinizing disorder that leads to the formation of small hyperkeratotic papules in seborrheic skin areas but can also affect mucosal membranes, nails, and the genitourinary areas. The histology shows acantholysis, hyperkeratosis, and dyskeratosis (the premature differentiation of keratinocytes). We identified a likely pathogenic variant in ATP2A2 (ENST00000539276.2: c.235G>A, p.Glu79Lys) in two probands (SF355, SF138). This variant segregates with disease in family SF355 . In addition to a diagnosis of IC/BPS, affected individuals in this family also report Hunner's ulcers, vulvodynia, and psoriasis. Vulvar localization and psoriasis are consistent with a diagnosis of Darier-White disease. The ATP2A2 gene encodes the sarco(endo)plasmic reticulum calcium-ATPase 2 (SERCA2) enzyme, which is involved in regulation of positively charged calcium atoms inside cells by pumping Ca2+ into the endoplasmic and sarcoplasmic reticulum. Altered intracellular calcium signaling may result in the abnormal epithelial development and dysregulated cell proliferation that lead to skin lesions. In addition, the SERCA pump is a major Ca2+ removal mechanism in small dorsal root ganglion (DRG) neurons. Lumbosacral DRG neurons mediate bladder sensation and are essential for normal voiding and pain detection. it is therefore possible that mutations in SERCA2 result in altered DRG neuron function and pain perception and also cause dysregulated cell proliferation in the urogenital tract resulting in the bladder balding and Hunner's ulcer often seen in IC/BPS. These findings suggest that further study of SERCA2 in bladder epithelium biology is warranted. Pathogenic variants in ATP2C1 cause Hailey-Hailey disease, another autosomal dominant skin disorder. Impairment of ATP2C1 leads to a dysfunction in the Golgi-associated human secretory pathway Ca2+/Mn2+ ATPase (hSPCA1) that results in recurrent blisters and erosions in intertriginous sites. Vulvar lesions are also possible. This causes pain, vulvodynia, pruritus, and the development of chronic malodorous abnormal growths at risk of infection with Staphylococcus aureus and Candida albicans. The symptoms are typically exacerbated with sweating, friction, and heat. We identified two private heterozygous variants in ATP2C1 in two unrelated individuals with IC/BPS. The SKAT analysis indicated that 6 additional individuals in our IC/BPS cohort have rare ATP2C1 missense variants, conferring an OR of 6.76 (See Table 6 and Tables S2 and S3, Supporting Information). It is possible that hypomorphic variants in ATP2C1 increase the risk of intertriginous erosion and result in the IC/BPS phenotype. Studies show that knockdown of SPCA1 results in disruption of Golgi morphology in HeLa cells, and reduction of the amount of Ca2+ stored in the Golgi lumen. The Golgi complex is tightly integrated into the urothelial cellular system, where it is crucial for the health of the blood-urine barrier, mainly through its association with uroplakins. One can hypothesize that mutations of ATP2C1 may also result in a disruption of Golgi morphology in urothelial tissue, impairing the formation of the blood-urine barrier, a hallmark of IC/BPS. We also identified a variant in the SIX5 gene (ENST00000317578.6:c.472G>A, p.Ala158Thr) known to cause BOR2 syndrome in one of our families with 3 generations of individuals with IC/BPS. Another family member has a bladder malformation. As BOR2 syndrome is known to have incomplete penetrance and associated kidney and lower genitourinary anomalies, the IC/PBS symptomology is potentially a mild manifestation of this genitourinary malformation syndrome. Two individuals with IC/BPS had rare variants in FZD8 (Table 5), which is a known candidate biomarker for IC/BPS. Keay et al. identified a glycosylated frizzled-related peptide inhibitor of bladder cell proliferation that is secreted specifically by bladder epithelial cells from affected individuals. This peptide inhibitor has homology to the putative sixth transmembrane domain of frizzled-8. It is possible that rare variations in FZD8 are contributory to the IC/BPS phenotype in these individuals, though much more investigation into the potential impact of this gene in a clinical syndrome. Limitations of this study include that our sample size is small. Therefore, we did not have the power necessary to run a genome-wide SKAT analysis and had to restrict the gene list to a small number of candidates. Additionally, we did not query structural variation (SV) or copy number variation (CNV). To extend these findings, we are attempting to enroll additional affected family members to screen them for the candidate genes discovered in this study. Moreover, we plan to follow the probands with ATP2C1 and ATP2A2 variants to see if interventions targeting their skin disorders will also ameliorate their IC/BPS symptoms. Future studies should also engage more family members and include parental ES and CNV assessment so that de novo versus inherited status can be determined, and ultimately future mechanistic studies will allow us to understand the role that ATP2C1 and ATP2A2 may play in IC/BPS. That said, it is also possible that the ATP2C1 and ATP2A2 variants are coincidental, and the individuals with these variants have co-occurring but non-overlapping disorders. In conclusion, we have identified variants in the genes SIX5, ATP2C1, and ATP2A2 that appear to explain aspects of the IC/BPS phenotype in affected individuals. As IC/BPS is a diagnosis of exclusion, we aim to use genetics to stratify the cohort, identifying families with overlapping phenotypic diagnoses like the SIX5 family. We hope this will allow us to finally discover a genetic cause of IC/PBS, which will lead to faster definitive diagnostics and genetic counseling while opening the door to more targeted therapeutics for this long-neglected disorder. Conflict of Interest The authors declare no conflict of interest. Author Contributions E.E., M.T., A.G.G., L.K., and C.A.B. contributed to the conceptualization and primary writing. E.E., M.T., P.S., J.P., V.Z., R.N.Y., S.B., C.B., P.B.A., A.H.B., and C.A.B. contributed to data collection, analysis and interpretation of results, discussion, review, and editing of the manuscript. Supporting information Supporting Information Click here for additional data file. Supplemental Table 1 Click here for additional data file. Supplemental Table 2 Click here for additional data file. Supplemental Table 3 Click here for additional data file. Acknowledgements The authors gratefully acknowledge the individuals who participated in this study. This work was funded by NIH 5U54DK104309-07. This publication was supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) under Grant number CDC 1U01DP006634-01-00 and by cooperative agreement RFA-DP-21-002. Additional funding was from the Boston Children's Hospital Intellectual and Developmental Disabilities Research Center Molecular Genetics Core Facility supported by P50HD105351 from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/NIMH U01 MH119690, and the Broad Institute Broad Children's Collaborative Grant Award. Data Availability Statement The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. |
PMC10000273 | Calcifying algae, like coccolithophores, greatly contribute to the oceanic carbon cycle and are therefore of particular interest for ocean carbon models. They play a key role in two processes that are important for the effective CO2 flux: The organic carbon pump (photosynthesis) and the inorganic carbon pump (calcification). The relative contribution of calcification and photosynthesis can be measured in algae by the amount of particulate inorganic carbon (PIC) and particulate organic carbon (POC). A microfluidic impedance cytometer is presented, enabling non-invasive and high-throughput assessment of the calcification state of single coccolithophore cells. Gradual modification of the exoskeleton by acidification results in a strong linear fit (R 2 = 0.98) between the average electrical phase and the PIC:POC ratio of the coccolithophore Emiliania huxleyi 920/9. The effect of different CO2 treatments on the PIC:POC ratio, however, is inconclusive, indicating that there is no strong effect observed for this particular strain. Lower PIC:POC ratios in cultures that grew to higher cell densities are found, which are also recorded with the impedance-based PIC:POC sensor. The development of this new quantification tool for small volumes paves the way for high-throughput analysis while applying multi-variable environmental stressors to support projections of the future marine carbon cycle. Calcifying algae play an important role in the ocean carbon cycle. The calcification state of these algae is studied at single-cell level using microfluidic impedance cytometry. This work demonstrates that the algal calcification state can be assessed by the electrical phase. Additionally, the influence of changes in the seawater carbonate chemistry on the calcification state is investigated. calcifying algae microfluidic impedance cytometry ocean carbon cycle PIC:POC ratio single-cell characterization Stichting voor Fundamenteel Onderzoek der Materie; Foundation for Fundamental Research on Matter source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 D. S. de Bruijn , D. B. Van de Waal , N. R. Helmsing , W. Olthuis , A. van den Berg , Microfluidic Impedance Cytometry for Single-Cell Particulate Inorganic Carbon:Particulate Organic Carbon Measurements of Calcifying Algae. Global Challenges 2023, 7 , 2200151. 10.1002/gch2.202200151 pmc1 Introduction A recent study by the National Academies of Sciences, Engineering, and Medicine published "a research strategy for ocean-based carbon dioxide removal and sequestration" to investigate the potential contribution of oceans to meet the global climate goals of the Paris agreement. One of the approaches in this study considers "ocean alkalinity enhancement" to alter the seawater chemistry via alkalinity (e.g., enhanced weathering ) and thereby remove carbon dioxide (CO2) from the atmosphere. However, it is unclear how this hypothetical enhancement will impact ocean life, and in particular calcifying organisms. Calcifying algae, like coccolithophores , greatly contribute to ocean alkalinity and the oceanic carbon cycle in general. They play a key role in two processes of the marine carbon cycle that both, in turn, are important for the effective CO2 flux: The organic carbon pump (photosynthesis) and the inorganic carbon pump (calcification). The fixation of CO2 via photosynthesis into organic carbon (particulate organic carbon (POC)) results in the drawdown of CO2 in the surface ocean, whereas the formation of the calcium carbonate exoskeleton (particulate inorganic carbon (PIC)) results, counter-intuitively, in a net release of CO2 (Ca2+ + 2HCO3 - - CaCO3 + H2O + CO2 ). Besides, the formation of the exoskeleton adds ballast to the algae, resulting in a sinking flux of carbon to the deep ocean. The ratio between the exported inorganic and organic carbon to deeper ocean layers (i.e., the "rain ratio") is of particular interest for ocean carbon models and the forecast of the future marine carbon cycle. The relative contribution of calcification versus photosynthesis in calcifying algae, and thereby the potential for inorganic and organic carbon that can be exported, is expressed by the algal PIC:POC ratio. Figure 1 a) SEM image of a single coccolithophore Emiliania huxleyi. b) Proposed classification of coccolithophores according to their PIC:POC ratio (via phase) and their electrical volume (via magnitude). The impedance magnitude at low frequency scales proportionally with the volume of a particle and is therefore given as the electrical volume. The phase response of calcified cells is expected to shift toward the phase response of polystyrene (PS) beads, because of their dielectric nature. c) Expected transition as a result of calcification or photosynthesis in coccolithophore cells. Among the major challenges in understanding impacts of climate change on calcifying algae, and their feed-back to the marine carbon cycle, is the potential for interactive effects across a wide range of environmental variables (e.g., CO2 concentration, temperature, nutrients, and irradiation). Lab-on-a-chip technology can greatly help testing the vast number of combinations of environmental variables, owing to its ability to precisely control culture conditions at high-throughput. Recent research demonstrates the biological response of microalgae to nanoplastics under 2000+ conditions. These systems typically work with small volumes, for which we would require a tool to analyze the PIC:POC ratio for small amounts of cells. Recent efforts show single-cell measurements using fluorescent labeling of the coccoliths, optics and dissolution of the exoskeleton by electrochemistry, and differentiation of cells with and without exoskeleton by impedance flow cytometry. Up till now, however, these methods have limited sensitivity or throughput or need an additional staining step. Other efforts focus on label-free analysis of the calcification state and coccolith mass using polarization-sensitive flow cytometry, requiring expensive and specialized optics. Impedance flow cytometry has the advantage over optical flow cytometry, as it is easier and cheaper to integrate in compact Lab-on-a-chip systems, but it lacks specificity (see perspective of ref. for more details). We therefore continue our earlier work on impedance flow cytometry, with novel components aimed to improve the sensitivity and throughput for assessing single-cell PIC:POC ratios, and validate this using independent measurements of PIC:POC ratios of bulk cell material. Such a more sensitive single-cell method may provide information on the variation in calcification state within a culture or population, in contrast to inorganic and organic carbon analysis in bulk. Impedance flow cytometry has been a widely studied and applied method since its introduction two decades ago. Recent advances show the ability to 1) assess the viability of cryopreserved primary human PBMCs, 2) monitor the cell status of spheroids and microcarriers, 3) determine the deformability, cell size, and membrane properties of human neutrophils, and 4) use modified red blood cells as multimodal standard particles. Impedance flow cytometry provides cell features in a non-invasive, label-free, and high-throughput (a few tens of cells per second for exploratory research up to several hundreds of cells per second for routine analysis ) manner. In general, the following features can be distinguished depending on the frequency with which we probe the cell: The cell size (<0.5 MHz), the cell membrane (1-10 MHz), and the cell's interior (>10 MHz). Here, we hypothesize that we can evaluate the PIC:POC ratio of single coccolithophore cells by means of their phase response at high frequency. The cell interior is probed at high frequencies (>10 MHz), where the cell membrane impedance is negligible. This leads to a measurable electrical contrast between the conductive cell interior and non-conductive (capacitive) calcium carbonate exoskeleton. Consequently, the phase response of calcified cells is expected to shift toward the phase response of non-conductive (capacitive) polystyrene (PS) beads with increased calcification, because of their dielectric nature . Likewise, calcification will increase the relative amount of PIC, thus shifting toward the phase response of PS beads, but also increasing the total electrical volume . In contrast, photosynthesis (increasing POC) reduces the PIC:POC ratio and increases the electrical volume of the cell. In this work we demonstrate a microfluidic impedance cytometer to measure the PIC:POC ratio of single coccolithophore cells at high-throughput. We start by artificially modifying the calcite exoskeletons with acid to investigate the extremes and we assess the sensor's performance by comparing the results with inorganic and organic carbon analysis on bulk material (referred to as C analysis). Finally, we study the influence of changes in atmospheric CO2 levels and the population density on the PIC:POC ratio of coccolithophore cells, which is also verified by bulk C analysis. 2 Results and Discussion 2.1 Data Representation and Error Estimation The measurements were performed using a differential impedance measurement setup as elaborately discussed in the material and methods section. We refer to Supporting Information for details on the processing of the complex impedance signal , the phase and magnitude response and finally the differentiation and normalization of the measured particles . Samples of coccolithophore cultures, grown exponentially under nutrient replete conditions, were directly introduced to the measurement system after spiking the sample with 5 mm PS reference beads. We observed multiple subsets of particles present in our samples . We differentiate between beads, cells, small debris, and dead cells . The size distribution of the reference beads is comparable to the standard deviation (+-0.16 mm) given by the manufacturer, indicating that the electric field in the sensing area of the system is homogeneous (more details on the design in Section 4 "Device Design and Fabrication"). For the discussion of the next results, we only consider the group characterized as coccolithophore cells and the monodisperse reference beads. Figure 2 a) Overview of the differential impedance measurement setup showing the coplanar electrode pairs, which are shielded by the ground electrodes. The channel height is 10 mm. b) The measured real and imaginary signal response of a single coccolithophore cell recorded at 0.5 and 27.5 MHz. c) Phase and magnitude response of a control and acid treated population of cells (decalcified), both mixed with reference beads. Several subpopulations can be identified based on their electrical size and phase response. d) Processed data after normalization with respect to the reference beads and removal of debris, dead cells, and double beads. The electrical diameter is defined as the cubic root of the impedance magnitude (see Section 4.3 "Data acquisition and processing"). 2.2 Data Acquisition and Analysis A control group of coccolithophore cells (no acid treatment) can be differentiated from a group of decalcified cells (dissolution of the exoskeleton by acid treatment), using the normalized phase . A reduction in mean diameter was also observed, as expected, owing to the dissolution of the exoskeleton. Our findings strongly suggest that the phase is an independent measure of the PIC:POC ratio for two reasons. 1) The normalized phase of decalcified cells (100% POC) is approximately independent of their cell size , thus their phase shift is independent of the absolute amount of organic content. 2) Single beads and double beads (corresponding to 100% PIC) have the same phase shift , thus their phase shift is also independent of the absolute amount of inorganic content. Hence, suggesting that the phase is mainly dependent on the fraction of inorganic and organic content, as is made plausible by the experimental results of cells with modified fractions of inorganic content, which will be discussed in Section 2.3 . Figure 3 a) Optical representation of the mean calcification state for each acid treatment. The amount of added acid increases from left to right (#1 to #4). b) The mean normalized phase versus the mean electrical diameter of each treatment (n > 1000 for each treatment and indication of the standard deviation by the error bars). c) Calibration of the sensor: normalized phase versus the PIC:POC ratio of each treatment via bulk C analysis. The PIC:POC analysis was performed twice for each treatment and four times for the control group. We observed a large spread in normalized phase, which can be caused by the measurement system or the biological variation. We have investigated the source of this variation by quantifying the measurement error of individual particles and compared this to error of a bulk measurement . From this comparison we can conclude that the biological variation is larger than our measurement error of single cells. Another important aspect of the data interpretation is the robustness of the measurements. Changes in the measurement system (e.g., contaminations in the sensing region during testing or differences in electrode-channel alignment between chips) can have a larger influence on the impedance response, than the subtle changes in the PIC:POC ratio we ultimately want to investigate . Therefore, the magnitude and phase response of the PS beads were always checked to ensure a fair comparison between different sets of measurements, which we will get back to later. 2.3 Calcification Gradient and Calibration Measurement To test the relationship between the normalized phase and the level of calcification, we created an artificial gradient in PIC:POC ratios through different acid treatments . The phase-diameter plot shows a clear linear correlation , as hypothesized . Note that we here assume that changes in the cell diameter scale linearly with changes in the cell volume, which is true for small changes in diameter. The spread in size and phase can be explained by the large biological variation across single cells within a culture. Additionally, the acid treatment did not result in a fully homogeneous dissolution of the samples, as was observed by optical inspection of the strongest acid treatment. However, the mean dissolution of PIC is a proper representative of the mean change in PIC:POC ratio (>1000 cells measured per treatment). We confirmed the relationship between the normalized phase and PIC:POC ratios with an independent method for quantifying the inorganic and organic carbon content in bulk coccolithophore culture (C analysis). Our results demonstrate a linear relation between the normalized phase and measured PIC:POC ratio . More details on the bulk C analysis can be found in Figure S8, Supporting Information. 2.4 CO2 Experiment and Population Density So far, we tested how artificial changes in the coccolithophore exoskeletons can be measured by normalized phase. The next step is to study changes in PIC:POC ratios as a result of natural perturbations in the carbon chemistry. To this end, we altered the carbon chemistry in culture media by aerating at a CO2 partial pressure (pCO2) of 400 and 1000 matm (see Table S2, Supporting Information). We grew the coccolithophore strain Emiliania huxleyi 920/9 (CCAP, UK) under these different CO2 conditions, and assessed their growth over a period of 5-7 days. At the last day of each experiment, we analyzed the bulk C of the cultures. Although mean PIC:POC ratios measured with bulk C analysis tended to decrease in response to higher CO2 levels in three out of the four experiments, the changes were not significant . Moreover, based on impedance measurements, the PIC:POC ratios remained largely unaltered in response to CO2 in all experiments. The unexpected lack of response to elevated pCO2 may have different causes. First, the response is different for every strain, some will be unaffected. Second, the physiological difference between the two treatments is relatively small and may become smaller after cells have grown as this causes a drift in the carbon chemistry (Table S2, Supporting Information). This is particularly evident in the experiments where cultures grew to higher cell densities (see also discussion below). Third, the technical error in our C analysis may possibly have overruled the differences between treatments, though this would not apply to the impedance measurements, in which we also did not observe changes in PIC:POC. Finally, other physiological changes, for instance the allocation of carbon to different macromolecules (carbohydrates, lipids), may possibly also alter the high frequency phase response and diminish the subtle difference between the CO2 treatments. Perturbations in the carbonate chemistry can be prevented by limiting the population density. For example, in our experiments that reached a biomass of 170 cells mL-1, total dissolved inorganic carbon (DIC) was reduced by 13% (Table S2, Supporting Information), while in treatments with a higher biomass build-up, this decrease was stronger. Comparing across the treatments thus not only involves variation in carbonate chemistry, and thereby PIC:POC ratios, but also differences because of variation in biomass build-up. For impedance data, we can only compare those experiments where the beads showed similar responses . These experiments include the ones reaching 220 and 450 cells mL-1 in the exponential phase (at growth rates of m = 0.83 d-1 and m = 0.99 d-1, respectively), and the one of 1750 cells mL-1 in stationary phase (m = 0.13 d-1). Across these experiments and CO2 treatments, we did observe a relationship between the measured PIC:POC ratio and normalized phase . The highest PIC:POC ratios and larger cell sizes were observed under lower cell densities, where drift in the carbonate chemistry could be more constrained. Vice versa, with increasing cell densities, the carbonate chemistry drifted and led to lower PIC:POC ratios. We note, however, that there are many variables apart from the population density when comparing across experiments, for example, the time of analysis in the light:dark cycle was different, which may play a role in calcification as well. Yet, despite the lack of consistent responses toward changes in pCO2 and the variation across experiments, we did observe a clear correlation between the normalized phase and the PIC:POC ratio, showing the potential application for impedance measurements in detecting cellular changes in calcification. Figure 4 a) Normalized phase versus the electrical diameter for cultures at different cell densities. b) Comparison between the normalized phase and PIC:POC ratio versus the population density at 220 cells mL-1 (n = 2), 450 cells mL-1 (n = 6), and 1750 cells mL-1 (n = 1), ignoring the influence of the CO2 treatments. c) 75% population-density contour plots for these cultures at different population density. The estimated PIC:POC ratio is shown on the right vertical axis and based on the calibration series in (b). d) The normalized phase versus the PIC:POC ratio for treatments of different population density and showing the different CO2 treatments. The error bars of the normalized phase are based on the spread (standard deviation) of all the single-cell measurements per treatment (n > 450 per treatment). The standard deviation of the PIC:POC ratio is the result of multiple C analysis per treatment (see number of treatments at caption b). The collection of all these single-cell measurements gives unique information about the heterogeneity of each treatment . A remarkable feature is the large variation in PIC:POC ratios for the cells from the experiment where biomass build-up amounted to 1750 cells mL-1. From the 450 cells mL-1 data, we postulate that the larger the cell size, the smaller the relative size of the exoskeleton, based on the shape of the contour. These observations cannot be made with traditional C analysis, as these contain bulk culture material and thus represent an overall mean of many cells with various diameters and with various calcification states. We can only compare different impedance measurements if the impedance response of the reference beads is equal, as mentioned before. The reference beads of the measurement series had a small shift in the mean magnitude and phase response compared to each other and therefore we observe a shift in the calibration curve between the normalized phase and PIC:POC ratio as well . Altogether, the similar trend in the normalized phase versus the PIC:POC ratio for both sets of experiments is a good indicator that our method is able to measure the average PIC:POC ratio via impedance. Figure 5 a) Raw impedance response of the reference beads for two sets of experiments was different (i.e., changes in the measurement setup or chip). b) As a result there is shift in the normalized phase-PIC:POC calibration, which stresses the importance of using reference beads. The error bars of the normalized phase are based on the spread (standard deviation) of all the single-cell measurements per treatment. The standard deviation of the PIC:POC ratio is the result of multiple C analysis per treatment. 2.5 Discussion Impedance flow cytometry has several advantages compared to inorganic and organic carbon analysis in bulk: 1) It requires small amounts of sample (tens of mL versus tens of mL), 2) it is a real-time and non-invasive method, 3) it can be potentially integrated in other Lab-on-a-chip systems, and 4) it gives information on the variation across cells within a culture or population. The major disadvantage is currently the poor robustness of our impedance sensor. At this point it was difficult to compare measurements done with different chips (i.e., slightly different alignment of the polydimethylsiloxane (PDMS) chip on the glass substrate with embedded electrodes), especially considering the relative small shift in phase we want to quantify. Therefore, the measurement system should be optimized, for example, by applying a different fabrication process to reduce the variation between chips. Additionally, we have studied only one species and strain (coccolithophore E. huxleyi 920/9), and it would be valuable to see if other algae phenotypes have a comparable response or need recalibration of the sensor. We also note that the PIC:POC approximation by the high frequency phase response ignores other physiological changes, for example, changes in the cell interior. In the future, recording an impedance spectrum and fitting an appropriate single cell model that captures all cell aspects might improve the determination of the PIC:POC ratio. 3 Conclusion We have demonstrated an impedance-based PIC:POC sensor for coccolithophore cells, enabling real-time, non-invasive, and high-throughput assessment of the calcification state and size of calcifying algae. Artificial modification of the exoskeleton with several acid treatments resulted in a very strong linear fit (R 2 = 0.98) between the average normalized phase and PIC:POC ratio. The effect of different pCO2 treatments (400 and 1000 matm) on the PIC:POC ratio of the coccolithophore E. huxleyi 920/9, however, was inconclusive. While PIC:POC ratios tended to decrease with elevated CO2 treatments, the variation was also high. We did find changes in the PIC:POC ratio as function of the population density. Cultures that grew to higher cell densities showed lower PIC:POC ratios, when testing across experiments and treatments, which was also recorded with our impedance-based PIC:POC sensor. Additionally, this single-cell method gives insight in the variation in size and PIC:POC within a culture of the same species or population and allows for real-time tracking of a single-cell or sample. The development of this new quantification tool for small volumes of sample (and cells), paves the road for future analysis in high-throughput systems while applying multi-variable environmental stressors to predict the future marine carbon cycle. 4 Experimental Section Device Design and Fabrication A large variety of electrode configurations have been presented over the years as recently reviewed by Zhu et al. A coplanar electrode configuration was designed and fabricated for differential impedance measurements . These coplanar electrodes were easy to fabricate, but less sensitive, than planar (facing) electrodes. Nevertheless, the sensitivity of coplanar electrodes can be optimized with particular design choices: A homogeneous electric field in the sensing region, a large electrode surface, a constriction in the channel, and shielding ground electrodes. The homogeneous electric field was realized by a small channel height (10 mm) with respect to the electrode separation (20 mm) and reduced the positional dependence of the particle in the sensing region. The large electrode surface increased the electrical double layer capacitance, thus reducing its influence at low frequency. The constriction channel (10 mm) reduced the total volume and therefore increased the sensitivity. Finally, the shielding ground electrodes reduced the stray capacitance and improved the signal-to-noise ratio. As a result the dielectric properties of single cells can be measured reliably and at high-throughput in comparison to our earlier work. The device consisted of a PDMS chip, with channel structures, bonded on top of a glass chip with microelectrodes. A standard photolithography process was used to fabricate buried tantalum/platinum electrodes in a borosilicate glass wafer (SCHOTT MEMpax, 500 mm thickness) using a BHF wet etch, Ta/Pt sputtering and a lift-off process. The 10 mm high SU-8 mold for casting the PDMS chips (Sylgard 184, Dow Corning) was made using a well-established lithography process. The bonding and the alignment of the glass-PDMS chip was done with a custom made alignment tool. Cell Cultivation and Preparation Coccolithophore E. huxleyi 920/9 (CCAP, UK) was cultured at 16.5 +- 0.5 degC and at a photon flux density of 130 +- 15 mmol photons m-2 s-1 under a 16:8 light:dark cycle. Seawater from the north sea was filtered with a 0.22 mm syringe filter and enriched with macronutrients, vitamins, and trace metals according to F/2 medium. The maximum population density did not exceed 2 x 106 cells mL-1. In the experiments testing for a CO2 effect, the population density did not exceed 6.0 x 105 cells mL-1, to reduce the drawdown of DIC. Cell densities were measured by a counting chamber and the growth rate m (d-1) was calculated according to (1) m=ln(CtC0)t-t0 with the population density c and the time t in days. Cell viability was monitored by checking the auto fluorescence of the chlorophyll. The number of dead cells was negligible under our test conditions. Moreover, cell viability after acid treatment was investigated by checking cell growth and regrowth of the exoskeleton. Both were observed within several hours after the acid treatment. Artificial modification of the calcium carbonate exoskeleton was performed by acid treatment of the samples. First, strong acid (0.1 m HCl) was added to the sample (100 mL) to (partially) dissolve the exoskeleton. The pH was constantly monitored and restored to its initial condition (pH 8) after 2 min using a strong base (0.2 m NaOH). This procedure was followed to create four different acid treatments using 0.60, 0.75, 1.3, and 1.5 mL of strong acid (0.1 m HCl). A fifth sample was unmodified and used as control measurement. All samples originated from the same culture flask. The CO2 treatments (400 and 1000 matm CO2 with synthetic air, Linde Gas) were prepared by continuously aeration of the culture medium and experimental systems (>30 mL min-1 in 100 mL culture). Impedance measurements were performed after five generation (five doubling times), requiring 4-6 days in total. Samples for standard bulk C analysis were taken at the end of each experiment, and after the impedance measurements. To this end, 15-70 mL of culture (depending on the population density) was filtered over glass-fiber filters (GF/F, 0.7 mm pore size, Whatman). The filters were stored at -20 degC and processed within 2 months after storage. Each glass-fiber filter was cut in half, where one was used to determine the total particulate carbon (TPC) and the other for POC. Prior to the POC analysis, the PIC was dissolved by adding HCl (0.2 m, pure grade) to the filters. Parts of the filters (24%) were folded into a 5 x 8 mm tin cup for C analysis on a Flash 1112 EA Analyser (Interscience, Breda). PIC was calculated as the difference between the TPC and POC analysis. PS reference beads of 5 mm (Sigma-Aldrich) where mixed with each sample before the start of an impedance measurement. The mixture of cells and beads was pulled through the chip by applying a negative flow rate of -0.6 mL min-1 using a neMESYS syringe pump (Cetoni) and 100 mL syringe (Hamilton), resulting in a residence time of less than a millisecond in the sensing area and enabling a throughput of 2.5 to 20 cells s-1 depending on the population density. Data Acquisition and Processing The complex impedance was recorded at 0.5 and 27.5 MHz simultaneously with a sampling rate of 115 kSa s-1 using a lock-in amplifier (Zurich Instruments HF2LI) and transimpedance amplifier (Zurich Instruments HF2TA). The input signal was set to 2 V peak-to-peak for both frequencies. The post processing of the impedance data was done in MATLAB (R2020a, MathWorks). A detailed description can be found in Supporting Information. The impedance magnitude |Z| was recorded at low frequency (0.5 MHz), below the cell's b-dispersion, to get information on the cell volume. The cell diameter scales with the cubic root of the impedance magnitude k|Z|0.5MHz3, where k is a calculated using the magnitude response of 5 mm PS beads. The phase was expressed at high frequency (27.5 MHz), above the cell's b-dispersion, to get information on the cell's interior and thereby exploiting the electrical contrast between the conductive cell interior and the resistive calcite exoskeleton. The high frequency was set to 27.5 MHz arbitrary, well above the cell's b-dispersion. Cells, beads, debris and dead cells were identified from the raw data . Typically particles smaller than 3.5-4.0 mm were classified as debris, this was verified by optical inspection . Cells with a normalized phase response smaller than -0.12 (calibration series) and -0.10 (other measurements) are considered as dead cells . Debris and dead cells were removed from the dataset for further processing of the results. A contour plot was created using the 2D kernel density function in Origin (2021b, OriginLab Corporation). The contour was set to 75% of the cells and determined by integrating the cells within the area of the contour with respect to the total area. A statistical two sample t-test was used to check whether the difference in normalized phase or PIC:POC ratio between the low and high CO2 treatment was significant (p < 0.05). The data was checked for normality using Shapiro-Wilk (p < 0.05). Conflict of Interest The authors declare no conflict of interest. Supporting information Supporting Information Click here for additional data file. Acknowledgements This work is part of the research program of the Foundation for Fundamental Research on Matter (FOM), which is part of the Dutch Research Council (NWO). The authors would also like to thank the Max Planck--Center for Complex Fluid Dynamics for part of the funding and they would like to thank their collaborators at NIOO-KNAW in Wageningen, the Netherlands. Special thanks to Paul ter Braak and Johan Bomer from the University of Twente for their help and expertise in the lab and the cleanroom fabrication. The authors would also like to thank Erik Reichman from NIOO-KNAW for the DIC analysis of the samples. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. |
PMC10000275 | Objective Aging is a complicated process that triggers age-related disease susceptibility through intercellular communication in the microenvironment. While the classic secretome of senescence-associated secretory phenotype (SASP) including soluble factors, growth factors, and extracellular matrix remodeling enzymes are known to impact tissue homeostasis during the aging process, the effects of novel SASP components, extracellular small noncoding RNAs (sncRNAs), on human aging are not well established. Methods Here, by utilizing 446 small RNA-seq samples from plasma and serum of healthy donors found in the Extracellular RNA (exRNA) Atlas data repository, we correlated linear and nonlinear features between circulating sncRNAs expression and age by the maximal information coefficient (MIC) relationship determination. Age predictors were generated by ensemble machine learning methods (Adaptive Boosting, Gradient Boosting, and Random Forest) and core age-related sncRNAs were determined through weighted coefficients in machine learning models. Functional investigation was performed via target prediction of age-related miRNAs. Results We observed the number of highly expressed transfer RNAs (tRNAs) and microRNAs (miRNAs) showed positive and negative associations with age respectively. Two-variable (sncRNA expression and individual age) relationships were detected by MIC and sncRNAs-based age predictors were established, resulting in a forecast performance where all R 2 values were greater than 0.96 and root-mean-square errors (RMSE) were less than 3.7 years in three ensemble machine learning methods. Furthermore, important age-related sncRNAs were identified based on modeling and the biological pathways of age-related miRNAs were characterized by their predicted targets, including multiple pathways in intercellular communication, cancer and immune regulation. Conclusion In summary, this study provides valuable insights into circulating sncRNAs expression dynamics during human aging and may lead to advanced understanding of age-related sncRNAs functions with further elucidation. Human aging is associated with increased susceptibility to age-related diseases due to alteration of biological processes. Here we identified changes in extracellular small noncoding RNA (sncRNA) expression with age from plasma and serum samples. A machine learning-based aging clock was developed using age-related sncRNAs and is capable of predicting individual age information. As a result of profiling the circulating sncRNA transcriptome we identified putative core biomarkers linked to the aging process. aging clock circulating sncRNAs human aging machine learning Oklahoma State University 10.13039/100007069 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Xiao P , Shi Z , Liu C , Hagen DE . Characteristics of circulating small noncoding RNAs in plasma and serum during human aging. Aging Med. 2023;6 :35-48. doi:10.1002/agm2.12241 pmc1 INTRODUCTION Heterogeneity of human lifespan and health outcomes occurs due to differential aging process. 1 , 2 , 3 Organismal aging is often accompanied by dysregulation of numerous cellular and molecular processes that triggers age-related pathologies such as tissue degradation, 4 tissue fibrosis, 5 arthritis, 6 renal dysfunction, 7 diabetes, 8 and cancer. 9 The highly proactive secretome from senescent cells, termed the senescence-associated secretory phenotype (SASP), is one of main drivers that cause age-related pathogenesis through intercellular communication. 10 The classical SASP includes secretome of soluble factors, growth factors, and extracellular matrix remodeling enzymes, 11 and it can transmit age-related information to the healthy cells via cell-to-cell contact. As one of the emerging SASP components protected by extracellular vesicles (EVs), ribonucleoprotein (RNP) complexes, and lipoproteins, 12 extracellular RNAs (exRNAs) are found in many biological fluids 13 and can bridge the communication between "donor" and "recipient" cells through endocytosis, inducing paracrine senescence and pro-tumorigenic processes. 14 , 15 Deep sequencing of human plasma exRNA revealed more than 80% of sequencing reads mapped to small noncoding RNAs (sncRNAs) in human genome, including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs). 16 Extracellular miRNA expression in plasma of mice changes with age and cellular senescence can affect age-related homeostasis throughout the body by circulating miRNA. 17 Other studies uncovered the roles of circulating miRNAs in age-related dysfunction such as osteogenesis imperfecta, 18 decreased myelination, 19 tumorigenesis, 20 and cardiovascular disease. 21 However, the molecular function of other circulating sncRNAs in aging and age-related diseases has been overlooked, and their expression profiles during human aging process must be further characterized. In this study, we determined the extracellular sncRNAs landscape during healthy human aging. Furthermore we generated an aging clock based on dynamic changes in extracellular sncRNAs and identified putative core sncRNAs with larger contribution weights in machine learning models for age-related risks prediction. To achieve this, we used 446 pre-selected small RNA-seq data from plasma and serum samples (age: 20-99 years) and employed differential expression analysis and linear or nonlinear association measurements to determine age-related sncRNAs as primary inputs for comprehensive machine learning modeling. Based on supervised machine learning models, aging estimators were created in high accuracy and sncRNAs candidates with top importance values in built models were considered as final age-related biomarkers. Additionally, pathway enrichment of targets of core miRNAs strengthens our viewpoint that extracellular sncRNAs change with age-related processes. 2 RESULTS 2.1 Overview of integrated human small RNAs dataset To profile sncRNAs features during human healthy aging, we obtained small RNA-seq datasets from the Extracellular RNA (exRNA) Atlas data repository ). 22 This work includes the studies for which information on age, health status, and gender, but only individuals having healthy aging process were retained for analysis. For datasets meeting the quality control standards established by the Extracellular RNA Communication Consortium (ERCC) (see experimental procedures), we created a bioinformatics procedure for reads mapping, processing, normalizing, categorizing, and modeling . As a result of these criteria, 302 plasma and 144 serum samples were used in this study, with a similar number of samples representing each gender ranging from 20-99 years old . As these datasets originate from distinct studies with multiple sampling and library preparations, there are clear batch effects after Counts Per Million (CPM) normalization . The ComBat function from the R package sva (v3.40.0) in Bioconductor 23 was employed to reduce or eliminate batch effect that may deviate from actual cross-study results . These corrected data were used for correlation measurements and machine learning training described below. FIGURE 1 Identifying practical computational models of healthy aging via plasma and serum small noncoding RNAs (sncRNAs). (A) Flow chart of data preprocessing, normalizing, batch effect correcting, and analyses of 446 blood samples. (B) Proportion of plasma and serum samples from healthy donors. (C) Distribution of age and gender in plasma and serum 2.2 Identification of expressed sncRNAs in plasma and serum To determine sncRNAs expressed during aging, we considered sncRNAs with >=1 CPM in at least 30% of individuals within an age group (young (20-30), adult (31-60), and aged (61+) groups) as expressed sncRNAs. As a result, there were 7953 and 6476 sncRNAs observed in plasma and serum samples respectively . Further, we identified highly expressed sncRNAs by increasing minimal CPM to 10, resulting in 1243 and 1139 sncRNAs retained in plasma and serum samples respectively . In terms of distribution of sncRNAs subtypes in three age groups, miRNAs account for a high proportion (26.5%-63.4%) of all sncRNAs in both plasma and serum, and their abundance consistently decreased with age . tRNAs increased and became the dominant sncRNA in aged group while expression of miRNAs were reduced in older individuals . The corresponding mapped reads are proportional to the number of each highly expressed subtype, even though miRNA showed relatively more sequencing reads than others in both plasma and serum . FIGURE 2 Highly expressed sncRNAs in plasma and serum. Subtype distribution of highly expressed sncRNAs, which meet the expression cutoff (>=10 CPM in >=30% of samples) among young (20-30 years), adult (31-60 years), and aged individuals (>=61 years) in plasma (A) and serum (B). Total sequencing reads of highly expressed sncRNAs among three age groups in plasma (C) and serum (D) 2.3 Exploring the correlation between sncRNAs and human aging We calculated the maximum information coefficient (MIC) (D. N. 24 ) to investigate both linear and nonlinear associations between sncRNAs expression and corresponding individual age. By employing batch-corrected data of expressed sncRNAs, we identified 364 and 1941 age-related sncRNAs from plasma and serum respectively . Intriguingly, piRNAs became the most abundant sncRNAs in MIC measurement, with the number of snRNAs representing the second largest . Similarly, the over-represented biological processes of miRNA targets were identified, and cellular response and epigenetic modification were enriched in plasma , while biosynthetic processes were significantly observed in serum samples . FIGURE 3 Identification of age-related sncRNAs. MIC-based age-related sncRNAs in plasma (A) and serum (B), identified by both MIC and total information coefficient (TIC) values >=0.7. Over-representation analysis of biological process of MIC-based age-associated miRNAs targets in plasma (C) and serum (D) (p-adjusted value <0.05) 2.4 Core feature selection of age-related sncRNAs As the expression of sncRNAs changes with age, further data-driven analysis was conducted to construct a human aging clock. MIC-based age-correlated sncRNAs were used as inputs to train regression models in plasma and serum samples. Compared to the linear models, such as Linear Regression (without feature selection) and Elastic Net (feature selection through regularization), the tree-based ensemble machine learning methods (including Adaptive Boosting, Gradient Boosting, and Random Forest regressors) showed stronger power of prediction with better performance in accuracy since its great capability of learning the underlying nonlinear patterns. With stably ideal performance in test subsets (Table S4), all models inputting age-correlated sncRNAs (MIC_plasma and MIC_serum) accurately predicted the ages of corresponding individuals in test sets, with average R 2 values greater than 0.96, root mean squared error (RMSE) values less than 3.7 years and mean absolute error (MAE) values less than 1.9 years . FIGURE 4 Performance evaluation of sncRNAs based aging clocks built by linear regression, elastic net, Adaptive Boosting, Gradient Boosting, and Random Forest approaches. Summary of R 2 value (A), root mean squared error (RMSE) (B), and mean absolute error (MAE) (C). (D) Model fit based on plasma MIC-based associated sncRNAs. (E) Model fit based on serum MIC-based associated sncRNAs. All model fits were constructed using Adaptive Boosting method. Due to the strong generalization ability in all ensemble learning methods, core sncRNAs associated with aging processes were determined by combined statistics and sum of importance ranks in the three methods was used as the criteria for core sncRNAs identification. As a result, there were 222 and 321 core sncRNAs overlapped in all three methods with MIC_plasma and MIC_serum as the inputs respectively (Table S5). Particularly, four snRNAs, three piRNAs, two small cytoplasmic RNAs, and one miRNA were identified as top core sncRNAs in plasma (Table 1). In serum samples, seven snRNAs, two tRNAs, and one small cytoplasmic RNA identified as top core sncRNAs in serum samples (Table 2). TABLE 1 Top core sncRNAs associated with age in plasma Model input Gene name RNA type Adaboost GB RF Sum of rank MIC_plasma piR-33,748 piRNA 3 1 1 5 MIC_plasma U5-L97 snRNA 1 2 2 5 MIC_plasma HY3-L319 scRNA 2 6 3 11 MIC_plasma U6-L1016 snRNA 7 7 4 18 MIC_plasma hsa-miR-11,181-3p miRNA 6 13 14 33 MIC_plasma HY1-L12 scRNA 22 4 10 36 MIC_plasma piR-61,840-L3 piRNA 16 3 18 37 MIC_plasma U7-L212 snRNA 18 17 11 46 MIC_plasma piR-49,811 piRNA 20 8 23 51 MIC_plasma U1-L72 snRNA 36 5 26 67 Note: Importance ranking from three ensemble learning methods and corresponding sum of rank. Abbreviations: Adaboost, Adaptive Boosting; GB, Gradient Boosting; RF, Random Forest. TABLE 2 Top core sncRNAs associated with age in Serum Model input Gene name RNA type Adaboost GB RF Sum of rank MIC_serum U5-L192 snRNA 2 9 6 17 MIC_serum U6-L317 snRNA 27 4 4 35 MIC_serum HY3-L199 scRNA 4 5 36 45 MIC_serum U2-L87 snRNA 34 13 28 75 MIC_serum U3-L6 snRNA 16 56 24 96 MIC_serum tRNA-Thr-AGT-1-1 tRNA 96 18 2 116 MIC_serum tRNA-Ala-AGC-8-1-tRF5 tRNA 37 44 71 152 MIC_serum U2-L1053 snRNA 135 3 15 153 MIC_serum U3-L119 snRNA 109 41 3 153 MIC_serum U6-L1640 snRNA 136 10 13 159 Note: Importance ranking from three ensemble learning methods and corresponding sum of rank. Abbreviations: Adaboost, Adaptive Boosting; GB, Gradient Boosting; RF, Random Forest. Notably, we also observed a gender-specific model performance. When male-only samples were used as training set for predicting female-only test sets or vice versa, there were core sncRNAs unique to one gender , with slightly lower performance in R 2 and RMSE values compared to the models trained in gender-mixed data . 2.5 Core miRNAs are involved in aging-related processes To gain further insight into extracellular sncRNAs potential functions in a microenvironment, we focused on miRNAs, which are well characterized in post-transcriptional gene regulation. The most ranked miRNA with the largest importance score in plasma and serum, hsa-miR-11,181-3p and has-miR-7845-5p (Table S5), were selected and their targets were separately predicted via the integration of eight miRNAs databases. The expressional profile of these two miRNAs in three age groups is in Figure S4 and corresponding targets are included in Table S7. As expected, these miRNA targets are enriched in canonical cell-cell communication pathways such as Sulfur relay system and Endocytosis pathways, as well as Immune development, Asthma and Ras signaling pathways that closely related to immune dysfunction and tumorigenesis during aging process . FIGURE 5 Top core miRNAs are associated with human aging and aging-related disease. (A) KEGG pathway enrichment analysis of core miRNA targets. Pathway terms are ranked by combined score in Erichr. 73 (B) Interaction network among core miRNAs (in red), targets (in blue), and corresponding regulatory proteins (in purple). Only targets and interacted proteins have validated function in cell senescence, human aging, and longevity (information from HAGR) are shown We also investigated the association between miRNA targets and protein coding genes previously validated in the human aging process from Human Aging Genomic Resources (HAGR), 25 and we found targets, including DDIT3, HLA-DQA1, PTK2B, TTR, and YWHAG, were experimentally identified to be associated with cancer progression, senescence, aging, and longevity (Table S8). Based on protein-protein interaction enrichment analysis, these targets were demonstrated to have regulatory relationship with hallmark proteins, such as PIK3R1, STAT3, IL7R, and JAK2 , which have function in cancer, immune response, and intercellular transduction, bolstering the probability that other non-miRNA sncRNAs also have functions in aging and aging-related diseases. 3 DISCUSSION Our study comprehensively profiled the relationship of extracellular sncRNAs with age in blood and built an aging clock of healthy individuals using sncRNAs linear and nonlinear correlated with age. Previously, age predictors were developed through DNA methylation sites, 26 transcriptome expression, 27 , 28 repeat elements, 29 microRNAs, 2 and protein abundance. 30 This study provides the first detailed analysis of relationship between circulating sncRNAs and age based on regression models and core sncRNAs whose expression changes with age, allowing reliable age prediction. From previous human biofluids studies, differential composition of small RNA has been reported in multiple biofluids. Godoy et al. 31 used 12 normal human biofluids including plasma and serum in their study and for mapping reads of corresponding RNA sequencing (RNA-seq), miRNA showed relative high fraction (63.8906%, median) in adult plasma compared to serum (36.0154%, median). However, the percentage of tRNA mapped reads in serum increased (42.2067%, median) and became the most abundant RNA biotype, while median value was 0.7759% in adult plasma. One study determined the diversity of small RNA in different biofluids, and tRNA showed the largest percentage of mapped reads (39.7%) in serum compared to plasma (5.8%) and whole blood (2.1%). 32 Also, in the Max et al. study, 33 they characterized extracellular RNAs (exRNAs) from both plasma and serum samples of the same healthy volunteers, and interestingly they showed substantial differences of small RNA composition, with higher proportion of miRNA in plasma and more tRNA reads in serum. We have some serum and plasma samples from the same individuals (Table S1) and consistent results were observed . Max et al. 33 also concluded that different biofluid types, even though they come from the same origin, plasma and serum show significant variable that impact exRNA profile. One of the reasons is that additional absorption and continuous degradation of exRNAs by retained blood clot will reduce exRNA abundance. 33 So proper exRNA isolation is essential and immediate platelet and cell debris depletion for plasma collection may avoid losses of exRNA characteristics as much as possible. It is of interest to identify a detectable increase of highly expressed tRNAs in aged individuals, and it has been reported that spleen and brain had the highest tRNA expression, 34 which may indicate unique and differential biological process happen as individuals age. A previous report similarly finds tRNAs were the second most abundant sncRNAs in healthy adults (20-40 years) when small cytoplasmic RNA was not mentioned. 35 Unlike tRNAs driving protein synthesis, tRNA-derived small RNAs (tsRNAs), including tRNA-derived fragment (tRF) and stress-induced tRNA halves (tiRNA), have been uncovered as aging process related sncRNAs. 36 Similar as human studies, the expression of tsRNAs increased during aging in Drosophila, 37 C. elegans, 38 and mouse brain cells. 39 Compared with healthy controls, differential expression of tsRNAs in age-related diseases has been employed in disease prediction such as Alzheimer's disease and Parkinson's disease, 40 ischaemic stroke, 41 and osteoporosis. 42 tsRNAs have roles not only in potential biomarkers, but also in expressional regulation of age-related mRNAs. 36 For example, 5'-tRFTyr from tyrosine pre-tRNA can silence PKM2, which is the inhibitor of p53, to cause p53-dependent neuronal death. 43 The number of highly expressed miRNA in our study displayed a decreased tendency in older group, and it has been observed in both plasma and serum. Both core miRNAs identified by machine learning models were found to have reduced expression as age increased, similar to decreased expression of a majority of age-associated miRNAs in whole-blood, 2 serum, 44 and peripheral blood mononuclear cells. 45 It has been previously demonstrated that circulating sncRNAs from serum samples show strong association with human aging, 46 while the human aging modeling based on regression relationship was not yet built. In our study, potential function of core sncRNAs was predicted via miRNA target prediction, and these targets showed enrichment in cancer, cell cycle, and longevity regulating pathways. There are overlapping genes included in both cancer and longevity regulation pathways, and this result was consistent with early study that profiled miRNAs expression between young and old individuals. 45 For example, increased PIK3R1 expression has been identified to impair anti-tumor effect through PI3K-Akt activation in breast and ovarian cancer chemotherapy. 47 , 48 Previous research determined that protein level of p85a, which is the subunit of PIK3R1, was elevated with age, and age-associated miRNAs that potentially target PIK3R1 were downregulated. 45 Studies in human aging also show that sequence variations within PIK3R1 gene are significantly correlated with longevity, 49 and individuals with different genotypes of PIK3R1 were associated with longevity through reduced mortality risk in cardiovascular disease. 50 Interestingly, both core miRNAs (hsa-miR-11,181-3p and has-miR-7845-5p) that are potentially involved in PIK3R1 regulation showed lower expression in aged individuals . The hsa-miR-11,181-3p has been used as biomarker for identification of glioma brain tumors from other brain tumor types. 51 By suppressing Wnt signaling inhibitor APC2, overexpression of hsa-miR-11,181-3p can promote Wnt signaling pathway and increase cell viability in colon malignant tumor cell line. 52 For has-miR-7845-5p, its expression in serum has been applied in constructing diagnostic classifier of ovarian cancer, 53 and higher expression was also observed in serum of patients with persistent atrial fibrillation. 54 Some direct targets of core miRNAs have been determined as drivers of age-related process. For example, protein tyrosine kinase 2b (PTK2B) is a tyrosine kinase activated by angiotensin II through Ca2+-dependent pathways to mediate ion channels as well as map kinase signaling pathway. 55 PTK2B is involved in cell growth, inflammatory response, and osmotic pressure regulation after activation and mutated PTK2B is statistically associated with hypertension in Japanese population. 56 PTK2B has also been reported in memory formation and corresponding protein variants can trigger cognitive dysfunction and higher prevalence of Alzheimer's disease. 57 As a nuclear protein that activated by DNA damage, DNA-damage inducible transcript 3 (DDIT3) shows increased expression and prevents gene transcription by dimerizing with transcription factors. 58 Specifically, DDIT3 plays role in endoplasmic reticulum (ER) protein processing and resulted ER stress promotes cardiomyocyte senescence in mouse hearts. 59 The function of most of age-associated sncRNAs identified in this study is unknown and further investigation into their function may provide meaningful results. We also observed the mild sex-dependent differences in the aging clock modeling. Similarly, a previous study indicated that sncRNAs differences between genders were minor 33 and sex-specific training sets have relatively low performance score in prediction compared to the gender-mixed training sets. During this process, some gender-dependent core sncRNAs were identified, including male-specific sncRNAs piR-31,143 and piR-48,977 in plasma, male-specific sncRNAs piR-33,527 and piR-57,256 in serum, female-specific sncRNAs hsa-miR-3789 and U5-L214 in plasma and female-specific sncRNAs U6-L989 and piR-30,597 in serum (Table S6). Further mechanistic study is needed to uncover their prospective role in aging and aging-related disease. A major limitation of our current study is the corresponding datasets utilized were developed by researchers for different, unique projects and with multiple RNA extraction protocols, which may bias extracellular RNA abundance. 35 Furthermore, trait information such as ethnicity, body mass, and smoking habits were not considered in our study due to the lack of information, and a more sophisticated and systematic sample processing and recording would help future research on big data-based human aging modeling. In conclusion, we provide a novel insight into the circulating sncRNAs profile of human aging. We developed predictive models in uncovering core sncRNAs and estimated age by utilizing meta-analysis based correlation measurement and machine learning modeling. The sncRNA dynamics with age provide valuable references for extracellular RNA study in aging, and the potential mechanisms of age-related intercellular communication by sncRNAs need further investigation. 4 EXPERIMENTAL PROCEDURES 4.1 Data acquisition and filtration Human small RNA-Seq datasets in the extracellular RNA (exRNA) Atlas data repository ) 22 were queried with studies filtered using the following requirements: (1) data were sequenced from plasma/serum samples; (2) samples have definitive age and gender information within each study; and (3) the donor of corresponding samples should have a healthy status and was sampled as a control individual for the study. As a result, two studies (Accession ID: EXR-MTEWA1ZR3Xg6-AN and EXR-TTUSC1gCrGDH-AN) were included in both plasma and serum studies, and two studies (Accession ID: EXR-TPATE1OqELFf-AN and EXR-KJENS1sPlvS2-AN) were obtained with only plasma and serum samples respectively and 366 plasma and 188 serum samples passed preliminary filtration. To avoid genes' expressional bias due to the low sequencing reads and host genome contamination, we only retained samples that met the quality control (QC) standards developed by Extracellular RNA Communication Consortium (ERCC). Briefly, individual dataset should have a minimum of 100,000 reads that aligned to annotated RNA transcript (including miRNAs, piRNAs, tRNAs, snoRNAs, circular RNAs, protein coding genes, and long noncoding RNAs), and ratio of transcriptome reads over total sequencing reads should be more than 0.5. Consequently, 302 plasma and 144 serum samples (Table S1) were retained for further analysis. 4.2 Quantification and batch effect removal To generate expression matrices of sncRNAs, read adaptors and low quality bases were removed using the Trim Galore (v0.6.5) wrapper. 60 Clean reads were aligned and quantified with bowtie2 (v2.4.4) 61 and samtools (v1.1.4) 62 through miRNAs and other sncRNAs annotation file from miRBase (Release 22.1) and the DASHR (v2.0) 63 database, respectively. The raw sncRNAs expression results were integrated and processed in R (v4.1.1) computational environment for identifying age-related sncRNAs after preprocessing. To correct for actual expression characteristics masked by sequencing depth variability, gene read counts were transformed into CPM values after measuring normalized library sizes by edgeR (v3.14) package. 64 Since there were still obvious batch effects observed via principal component analysis , we conducted batch removal using the ComBat function in sva package (v3.40.0) 23 and processed CPM-based data showed improved sample clustering by age . Batch-effect corrected data were used for identifying maximum information coefficient and constructing machine learning models described below. 4.3 Identification of association between sncRNAs and age To select the sncRNAs representative of the age prediction model, the maximal information coefficient (MIC), 24 which permits the identification of important, difficult-to-detect associations, 65 was used to identify and screen the linear or nonlinear correlations between each sncRNA expression (X) and the individual's chronological age (Y). Reshef et al. 24 reported that MIC - r2 to be near zero for linear relationships and MIC - r2 > 0.2 for nonlinear relationships, where r2 is the coefficient of determination (R 2). We also employed total information coefficient (TIC) to evaluate the power of independence testing between X and Y. 66 The sncRNAs having both MIC and TIC values greater than 0.7 with actual age were retained for building models. 4.4 Comprehensive machine learning modeling The corrected expression data of sncRNAs selected from differential expression analysis and MIC-based correlation measurement were used for machine learning modeling. Since sncRNAs expression inputs could be seen as the explanatory variable X, which is a high dimensional vector, the modeling process was performed as a regression analysis problem and was formularized as: (1) y=f^X where X denotes the sncRNA inputs, y denotes individual's age, and f^ denotes the fitted mapping function. Ensemble learning including Adaptive Boosting, Gradient Boosting, and Random Forest were leveraged in this study, taking advantage of their strong generalization ability achieved by multiple weak learners combination. 67 Based on manual parameter tuning, the parameter "number of estimators," which is the number of weak learners (i.e., the regression tree in this study) to be integrated in model fitting, was determined in each specific model based on the overall performance (RMSE, R 2, and MAE, showed in Table S10). The performance of ensemble learning is compared with linear regression and elastic net. The corresponding importance of each sncRNA was calculated as impurity-based feature score (sum to 1), which can be used to determine the fraction of sncRNA that it makes contribution to distinguish. 68 Potentially core sncRNAs were determined by sorting the corresponding sum of ranks of their importance values in each ensemble learning model. Since the number of samples is different in each age group (young, adult, and aged), simple k-fold cross-validation may cause uneven sampling and then trigger bad model performance due to over-fitting. Therefore, stratified k-fold cross-validation is a better option to avoid this issue by selecting approximately the same proportions of samples in each pre-set age group to the training set . In this study, we stratified fivefold cross-validation based on the overall sample size. The regression modeling was conducted under Python 3.8.8 and scikit-learn 0.24.1. 69 4.5 Targets prediction of age-related miRNAs To better understand the potential function of circulating sncRNAs changing with age, we primarily predicted the targets of miRNA candidates by using multiMiR R package (V3.14), 70 which integrates eight microRNA-target databases (DIANA-microT, ElMMo, MicroCosm, miRanda, miRDB, PicTar, PITA, and TargetScan). 4.6 Functional enrichment analyses Functional enrichment analyses of genes targeted by age-related miRNAs performed through Enrichr gene list-based enrichment analysis tool. 71 We used the combined score, which is a combination of the P value and z-score, to offset the false positive rate caused by the different length of each term and input sets. For direct miRNAs functional enrichment, an over-representation analysis was performed via miRNA Enrichment Analysis and Annotation Tool (miEAA 2.0), 72 with expressed miRNA sets as the background set and P values were adjusted using Benjamini-Hochberg (BH) procedure. AUTHOR CONTRIBUTIONS PX performed the experiments and contributed to project design, data collection, execution of machine learning modeling and analysis, and manuscript writing. ZS and CL contributed to experimental design and execution of machine learning modeling and analysis. DEH contributed to data collection, analysis, and manuscript writing. FUNDING INFORMATION Not applicable. This research did not receive external funding. CONFLICT OF INTEREST The authors have no conflicts of interest to declare. Supporting information Figure S1. Click here for additional data file. Figure S2. Click here for additional data file. Figure S3. Click here for additional data file. Figure S4. Click here for additional data file. Figure S5. Click here for additional data file. Table S1. Click here for additional data file. Table S2. Click here for additional data file. Table S3. Click here for additional data file. Table S4. Click here for additional data file. Table S5. Click here for additional data file. Table S6. Click here for additional data file. Table S7. Click here for additional data file. Table S8. Click here for additional data file. Table S9. Click here for additional data file. Table S10. Click here for additional data file. ACKNOWLEDGMENTS The authors thank the Oklahoma State University Office of the Vice President for Research for computational support for data storage and analysis. DATA AVAILABILITY STATEMENT All of the small RNA-Seq raw data (FASTQ) files and corresponding metadata are available directly from Extracellular RNA (exRNA) Atlas data repository with study ID (EXR-MTEWA1ZR3Xg6-AN, EXR-TPATE1OqELFf-AN, and EXR-TTUSC1gCrGDH-AN), or from the database of Genotypes and Phenotypes (dbGaP) with accession ID phs000727.v1.p1 for study EXR-KJENS1sPlvS2-AN. |
PMC10000276 | BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild-type SARS-CoV-2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full-length spike protein sequence-based mRNA vaccine as the "priming" shot and developed a recombinant trimeric receptor-binding domain (RBD) protein vaccine referred to as RBD-HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD-HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5-included SARS-CoV-2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long-lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD-HR/trimer following two-dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD-HR/trimer vaccine becomes an appropriate candidate for a booster immune injection. We prepared a Delta full-length spike protein sequence-based mRNA vaccine and developed a recombinant trimeric receptor-binding domain (RBD) protein vaccine . Later, the mRNA vaccine was injected as the "priming" shot, and the RBD-HR/trimer vaccine was used as a third heterologous booster . heterologous vaccination mRNA vaccine recombinant RBD vaccine SARS-CoV-2 National Science Foundation for Excellent Young Scholars32122052 National Natural Science Foundation Regional Innovation and DevelopmentU19A2003 source-schema-version-number2.0 cover-dateApril 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Peng D , Zhao T , Hong W , et al. Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5-included SARS-CoV-2 variants than homologous vaccination of mRNA vaccine. MedComm. 2023;4 :e238. 10.1002/mco2.238 pmc1 INTRODUCTION Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic infectious disease called the coronavirus disease 2019 (COVID-19) and threatened public health considerably. To fight against SARS-CoV-2, vaccination has been one of the most effectual tactics so far. Currently, 11 candidate vaccines, based on adenovirus-based vector, mRNA, protein subunit, and viral vector, have been approved globally against the epidemic. Among them, BNT162B2 (mRNA) from Pfizer-BioNTech, ChAdOx1 nCoV-19 (adenovirus-based vector) from AstraZeneca, mRNA-1273 (mRNA) from Moderna, and NVX-CoV2373 (protein subunit) from Novavax are some of the representative vaccines. These COVID-19 vaccines effectively protected against symptomatic diseases and fatal outcomes arising from the ancestral SARS-CoV-2. 1 , 2 , 3 , 4 Nevertheless, as the continued evolution of SARS-CoV-2, the emergence of new variants brings further challenges to the development of vaccines. Notably, the dominant variant, Omicron (B.1.1.529), with a ton of spike protein mutations, was highly transmissible and impaired the population protection conferred by the currently marketed vaccines. 5 For instance, 2-4 weeks after BNT162B2 vaccination, the neutralizing ability against Omicron variant was reduced 30-fold compared to the WA1/2020 strain. 6 Additionally, another study showed a 22-fold difference in geometric mean titer (GMT) of 50% neutralization between the WA1/2020 strain and Omicron variant (1963 vs. 89). 7 Recently, a series of lineages of Omicron variants, such as BA.2, BA.3, BA.2.12.1, BA.4, and BA.5 (BA.4/5), have been identified. Among them, the newest members of Omicron, BA.4/5, are dominant in South Africa and the United States and deserve more attention. 8 Although the spike protein mutations of BA.4/5 are comparable to those of BA.2, 9 the neutralization escape abilities of BA.4/5 were remarkable increased, which is a more significant obstacle for vaccine development. 10 In light of this urgent situation, a third booster dose was proposed to be vaccinated for reversing the impaired efficacy of vaccines against Omicron. 11 Muik et al. found that three doses of BNT162B2 could remarkably increase the neutralizing capacity against Omicron. 12 Similarly, the homologous mRNA-1273 booster could also improve the efficacy of the two-dose mRNA-1273 vaccination against Omicron variant. 13 Although the neutralizing capacity could be enhanced by a third booster, the effectiveness against the BA.4/5-included Omicron variants was still dramatically impaired. 14 Recent studies implied that a third heterologous booster after two-dose priming vaccination substantially increased protection. For instance, a third heterologous protein subunit booster after two doses of inactivated whole-virion vaccines could provide more efficient neutralization than a third homologous inactivated whole-virion booster. 15 However, the effects of a third recombinant protein subunit heterologous booster after two doses of mRNA priming vaccines have never, to our knowledge, been evaluated so far. To investigate whether the heterologous prime-boost vaccination of recombinant protein vaccine and mRNA vaccine could induce stronger immune response, the NIH mice were injected intramuscularly with two doses of mRNA vaccine, followed by the third dose of receptor-binding domain (RBD)-HR vaccine. As a control, NIH mice were injected with three doses of PBS, mRNA vaccine, or RBD-HR vaccine, respectively. The vaccinated serum and tissue samples were collected to evaluate vaccination-induced humoral and cellular immune responses. 2 RESULTS 2.1 The heterologous vaccine induces higher titers of RBD-specific binding antibody To investigate whether the third protein subunit heterologous booster could improve the protective efficacy of vaccination over a homologous booster, we designed a Delta full-length spike protein sequence-based mRNA vaccine and developed a recombinant trimeric Delta-derived RBD protein vaccine (containing L452R and T478K) referred as RBD-HR/trimer 16 . The endotoxins of the mRNA vaccine are less than 15 EU/dose or less than 30 EU/mL, and the quality of the RBD/HR vaccine has been approved. 16 For the broad potential of MF59-like adjuvant in antibody and T cell responses, MF59-like adjuvant was selected to serve as an adjuvant to improve the immunogenicity of the RBD-HR/trimer protein. 17 , 18 In the present study, the NIH mice were intramuscularly vaccinated with mRNA vaccine on day 0 and 21. After two-dose vaccination, the mice were immunized with a third-dose mRNA or RBD-HR/trimer on day 42 . To verify the effectiveness of mRNA vaccines, we designed vaccines with three measurements of low (1 mg), medium (5 mg), and high (10 mg). Currently, in most preclinical studies, the COVID-19 vaccine is administered at intervals of 21 days. To simulate clinical trials, a third dose of the vaccine is given 3 months after the second dose (long-term immunization). Serum samples were collected on days 56, 84, 115, and 153, and the cytokines were detected within a few days of sampling . As a control, mice were immunized with three doses of PBS, mRNA, or RBD-HR/trimer (10 mg), respectively. The levels of RBD-specific lgG titers in serum collected on day 56 (on day 125 for long-term vaccination) were detected by enzyme-linked immunosorbent assay (ELISA). As expected, a range dose (1, 5, and 10 mg) of mRNA vaccines elicited high specific anti-RBD IgG levels . It is worth noting that the heterologous vaccination with RBD-HR/trimer significantly increased the binding antibody titers . The trend of binding antibody titers among the long-term immunization was aligned with the above . In the subsequent experiment, the serum samples from the mice vaccinated with a 1 or 5 mg dose of mRNA vaccine were utilized. FIGURE 1 Preparation and characterization of mRNA-loaded liposome and recombinant receptor-binding domain (RBD)-HR/trimer protein: (A) the schematic of Delta full-length spike mRNA construct with mutations; (B) preparation of the mRNA vaccine. Alcohol phases formed by cholesterol, DMG-PEG2000, DOPE, and E1-1 lipid were mixed with mRNA aqueous phase at a proper ratio to formulate mRNA vaccine; (C) schematic of the recombinant RBD-HR/trimer protein construct. Our protein comprises an RBD derived from Delta with L452R and T478K mutations, HR1, and HR2 domains. Domains and elements are marked. HR1 and HR2, heptad repeats 1 and 2; NTD, N-terminal domain; RBD, receptor binding domain. An N-terminal GP67 signal peptide was designed for secretion. Parts (A) and (B) were created by BioRender. FIGURE 2 The schematic diagram and anti-IgG responses of heterologous and homologous immunization processes: (A) the schematic diagram of the immunization program. NIH mice were intramuscularly immunized with 1, 5, or 10 mg mRNA vaccine on days 0 and 21. A third heterologous booster, receptor-binding domain (RBD)-HR/trimer (10 mg), or a homologous booster mRNA vaccine, was vaccinated on day 42, for the long-term immunization, mRNA vaccine was injected on days 0 and 21, and RBD-HR/trimer booster was given on day 111. mRNA group: three doses of mRNA vaccine; RBD-HR/trimer group: three doses of recombinant RBD-HR/trimer vaccine; mRNA + RBD-HR/trimer group: two doses of mRNA vaccine followed by a heterologous booster with RBD-HR/trimer. The serum samples were collected on day 56 (B) and day 84 (C); (B) the endpoint titers of RBD-specific IgG in sera collected on day 56 were assayed by enzyme-linked immunosorbent assay (ELISA); (C) the detection of the titer of anti-RBD IgG in serum samples collected 125 days after the third dose was performed by ELISA. Part (A) was created by BioRender. The significance of differences among groups was conducted by a One-way ANOVA analysis followed by Tukey's multiple comparison post hoc test. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant. 2.2 Heterologous vaccination benefits broad-spectrum neutralization response against BA.4/5-included SARS-CoV-2 variants To evaluate whether the heterologous vaccination could give the better protective efficacy than homologous vaccination, mice were intramuscularly injected with "1 mg" mRNA vaccine in the homologous mRNA group, and sera were collected on day 84 and 153 (long-term vaccination) since the first immunization, and conducted the pseudovirus neutralization assay . As expected, the homologous mRNA vaccination elicited considerable titers of neutralization antibodies against SARS-CoV-2 variants, and the third heterologous vaccination with RBD-HR/trimer could further provide higher titers of neutralization antibody . For the homologous mRNA group, the GMTs of 50% neutralization to prototypes, Alpha, Beta, Gamma, Lambda, and Delta, were 2179, 3251, 3122, 1353, 9143, and 5950, respectively. Notably, boosting with the RBD-HR/trimer vaccine significantly increased the neutralizing activities primed by the mRNA vaccine. Compared to the homologous vaccination with mRNA vaccine, the GMTs of 50% neutralization in heterologous vaccination group against prototypes, Alpha, Beta, Gamma, Lambda, and Delta, were observed to increase to 9-, 3.9-, 6.5-, 10.6-, 2.7-, and 2.1-fold, respectively . Similar results were observed in long-term heterologous and homologous programs . FIGURE 3 Heterologous group induces stronger broad-spectrum neutronization response against BA.4/5-included Omicron variants: (A and B) broad-spectrum neutronization responses against various pseudoviruses were determined; (C) neutralizing antibody titers against BA.4/5-included Omicron variants were determined; (D and E) representative images (D) and analysis (E) of flow cytometry represent the blockade of receptor-binding domain (RBD)-Fc (Omicron) binding to human ACE2 receptor; (F and G) the flow cytometry images (F) and analysis (G) of the inhibition of RBD-Fc (Omicron) binding to human ACE2 receptor. NIH mouse were intramuscularly injected with 1 mg mRNA in parts (A)-(C) and 5 mg mRNA in parts (D)-(G) in the homologous mRNA and heterologous groups. Serum samples in parts (A), (C), and (D) were collected on day 84, and serum samples in parts (B) and (F) were collected 153 days after the first dose (long-term groups). One-way ANOVA analysis followed by Tukey's multiple comparison post hoc test was conducted in parts (A)-(C), (E), and (G). All error bars represent SEM about the mean. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; ns, not significant. Omicron BA.1 sub-lineage used to be the dominant variant because of numerous spike protein mutations. Several months later, BA.2 rapidly outcompeted and replaced the BA.1. 19 Recently, new sub-lineages of Omicron (BA.2.12.1 and BA.4/5) have become the dominant strains in South Africa and the United States. It has been reported that BA.2.12.1 and BA.4/5 significantly escaped the immune response caused by previous infection or vaccination. 20 , 21 To further evaluate the homologous or heterologous vaccination-induced neutralizing potencies against the Omicron sub-lineages, sera were collected in the long-term groups on day 153 for the assay of neutralizing antibody. As expected, the neutralizing capacities induced by homologous mRNA vaccination against various sub-lineages of Omicron were remarkably impaired. Remarkably, heterologous vaccination with RBD-HR/trimer exhibited stronger neutralization potency against Omicron subvariants, including BA.4/5, and the GMTs of 50% neutralization to BA.1, BA.2, BA.2.12.1, BA.3, and BA.4/5 pseudovirus could reach 4842, 11,284, 3750, 1551, and 2477, respectively. Whereas, in the homologous mRNA group, the GMTs of 50% neutralization determined 786, 796, 809, 734, and 312, respectively . For the purpose of verifying the underlying mechanism of viral neutralization, the blockade of binding between cell-surface ACE2 receptor and RBD-Fc (Omicron) was detected by the flow cytometry. In-line with the results of the pseudovirus assay in two immunization programs at different intervals, heterologous vaccination also showed a higher inhibition rate between RBD-Fc (Omicron) and human ACE2 receptor than homologous mRNA vaccination . Notably, the inhibition rate in the shorter program was better, which underlined the importance of getting booster shots at the proper time . These results demonstrated that the heterologous vaccination with protein subunits could be a better strategy for inducing stronger humoral immunity than the homologous vaccination of mRNA vaccines. 2.3 Heterologous vaccine elicits more robust T cell immune response in vivo T cell responses have an essential effect on preventing SARS-CoV-2 and are primary determinants of clinical outcome. 22 For the homologous mRNA group, mice were intramuscularly injected with 5 mg mRNA. We detected CD4+ and CD8+ T cell responses against an RBD of SARS-CoV-2 in our study. Single-cell suspension of splenic lymphocytes was prepared to evaluate the further effects of heterologous vaccination with RBD-HR/trimer on the cellular immune response. We detected the secreted cytokines (IL-4 and IFN-g) after being stimulated with the RBD protein at 37degC for 72 h by flow cytometry and ELISA. We found that the levels of secreted IL-4 and IFN-g were higher in the heterologous vaccination and homologous protein vaccine group, indicating a strong T cell response could be induced by RBD-HR/trimer vaccine. It was reported that the mRNA vaccine could cause a solid IL-2-associated T cell response, 23 whereas the protein vaccine could not. Notably, the heterologous vaccination and homologous mRNA vaccination induced comparable IL-2-associated CD8+ T cell response . Memory T cell responses are essential in accelerating and enhancing immune response, especially when reinfected with the same pathogen. 24 , 25 In addition, immunological T cell memory response could also provide protective immunity against diverse variants. 26 We evaluated the subsets of the spleen effector memory (CD44+CD62L-) T cells on day 49. The number of the CD4+ and CD8+ effector memory T cells was higher than both mRNA and RBD-HR/trimer homologous vaccination groups . In a word, the heterologous vaccination with RBD-HR/trimer induces stronger cellular immunity than the homologous mRNA vaccine. FIGURE 4 Heterologous vaccine elicits a stronger T cell immune response in vivo. Lymphocytes were collected from isolated spleens and stimulated with receptor-binding domain (RBD) (10 mg/mL) proteins for 72 h: (A) representative flow cytometry dot plots of RBD-specific IL-4-producing CD4+ (top) and CD8+ (bottom) memory T cells (CD44high B220-MHC-II-CD4+ and CD44high B220-MHC-II-CD8+); (B) the levels of IL-4 in cell supernatant were analyzed by enzyme-linked immunosorbent assay (ELISA); (C) the flow cytometry images of RBD-specific CD4+IFN-g+ and CD8+ IFN-g+ memory T cells (CD44high B220-MHC-II-CD4+IFN-g+ and CD44high B220-MHC-II-CD8+IFN-g+); (D) the levels of RBD-specific IFN-g-producing CD4+ (top) and CD8+ (bottom) memory T cells; (E - G) The percentage of RBD-specific IL-2-producing memory T cells (CD44high B220-MHC-II-CD4+IL-2+ and CD44high B220-MHC-II-CD8+ IL-2+) in the spleen was detected by flow cytometry; (H and I) the percentage of CD4+ (G) or CD8+ (H) effect memory T cells (CD4+CD44+ CD8+CD44+CD62L-) in lymph node was determined. 2.4 Heterologous vaccination induces further long-lasting memory response Long-lasting memory response provides rapid and effective protective immunity when reinfected. 27 For the homologous mRNA group, mice were intramuscularly injected with 5 mg mRNA. To detect whether the heterologous vaccination would induce further memory response with RBD-HR/trimer, we analyzed the T follicular helper (Tfh), plasmablast response, and germinal center (GC) formation, which are essential for the long-lasting memory response. 28 Moreover, the GC B and Tfh cells were closely related to neutralizing antibody responses. 18 The results show that the heterologous vaccination with RBD-HR/trimer could enhance Tfh , plasmablast , and GC B response . It is worth noting that the frequency of Tfh and GC B cells was the highest in the heterologous vaccination group. Thus, these results suggested that the heterologous vaccination with RBD-HR/trimer could induce a higher magnitude long-lasting memory immune response than the booster with mRNA vaccine. FIGURE 5 Heterologous vaccination induces further long-lasting memory response in NIH mice: (A) typical pseudocolor flow cytometry plots showing Tfh cells; (B) typical pseudocolor flow cytometry plots showing plasmablast cells; (C-E) frequencies of the Tfh (C), plasmablast (D), and GC B (E) cells in lymph nodes were analyzed. The significance of differences among groups was conducted by a One-way ANOVA analysis followed by Tukey's multiple comparison post hoc test. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant. 3 DISCUSSION BA.2.12.1 and BA.4/5, the emerging sub-lineages of the B.1.1.529 (Omicron) variant, have displaced as the new dominant strains in South Africa and the United States, and currently marketed vaccines could not provide enough protection against the newly emerged sublineages. 29 A third boost shot is, therefore, widely requested. The sequential immunization was proposed to elicit vaccine-induced immune protection, and the heterologous booster could remarkably improve the potency of the vaccination. 30 In addition, combinations of different vaccines, including ChAdOx1 nCoV-19 (ChAd)/BNT162b2 (BNT), BNT/ChAd, ChAd/mRNA-1273, ChAd/BBV152, CoronaVac/BNT, CoronaVac/Convidecia, and Ad26/BNT, have already been validated as well. 31 , 32 , 33 , 34 , 35 In addition, the heterologous recombinant protein vaccine booster (ZF2001) after inactivated priming vaccines has already shown dramatically enhancement in anti-RBD response and neutralizing antibody response. 36 The underlying mechanism may be associated with the heterologous vaccination-induced stronger germinal center reactions and a more varied immunoglobulin repertoire. Nevertheless, as far as we know, the sequential immunization with the combination of mRNA and protein vaccine is still vacant. In the present study, the protein vaccine RBD-HR/trimer was used as the third-dose heterologous booster after the two-dose administration of mRNA vaccine. SARS-CoV-2 mRNA vaccines could elicit a superior GC response compared to a recombinant protein formulated with an MF59-like adjuvant (rRBD-AddaVax) after a single dose. 18 However, in our study, we found no significance between three doses of homologous RBD-HR/trimer vaccine and homologous mRNA vaccine in GC response. Liao et al. suggested that SARS-CoV-2 S-trimer with MF59-like adjuvant could also induce GC responses with a low dose. 37 Both of the homologous groups elicited comparable GC responses, which may benefit from the trimer structure of the RBD-HR protein vaccine. 16 , 38 , 39 Notably, the heterologous RBD-HR/trimer vaccine booster following two doses of mRNA vaccine dramatically enhanced the GC responses. A recent study suggested that an mRNA-Omicron booster could not elicit stronger humoral immunity and cellular immunity when compared with an mRNA-1273 booster for mRNA-1273-vaccinated macaques. 40 In addition, we and others also have shown impaired thermostability and antigenicity of the recombinant Omicron RBD or S1. 41 Therefore, in our study, we designed the recombinant RBD protein based on Delta rather than Omicron for the effective broad-variant neutralization of Delta variant. As expected, the heterologous recombinant protein vaccine booster provides enhanced immunity and protection than the homologous mRNA vaccine. In our research, the third heterologous booster of self-assembled recombinant RBD-HR vaccine primed with two mRNA vaccines could enhance humoral and cellular immune response, manifested by the higher anti-RBD IgG, stronger neutralizing antibody, and IFN-g-secreted T cells. Furthermore, the heterologous vaccination could induce stronger effector memory response than both homologous RBD-HR and mRNA vaccinations. In addition, the heterologous vaccination induced a higher plasmablast response than the homologous mRNA group and induced the highest GC B cell and Tfh response than both homologous groups, which indicated that the higher long-lasting memory response could be elicited by heterologous vaccination with protein vaccine. Therefore, our study provided a solid indication of the heterologous boosting strategy against COVID-19, and a third heterologous protein subunit booster becomes an appropriate candidate after two doses mRNA vaccine. 4 MATERIALS AND METHODS 4.1 Materials The mRNA vaccine we prepared could be translated into the SARS-CoV-2 Delta (B.1.617) full-length spike protein sequence when injected. Recombinant RBD-HR/trimer protein vaccine was developed as previously reported. 16 4.2 Cells As previously reported, 42 we generated the 293T cells, which were capable of stably expressing human angiotensin-converting enzyme 2 receptor (293T/ACE2). The cells were cultured with Dulbecco's modified Eagle's medium (DMEM, Thermo Fisher Scientific, USA) supplied with 10% fetal bovine serum, 0.1 mg/mL Streptomycin and 100 U Penicillin at 37degC with 5% CO2. 4.3 Animals NIH female mice aged 6-8 weeks were purchased from Vital River (Beijing, China) and housed in a specific pathogen-free environment of the State Key Laboratory of Biotherapy. 4.4 Vaccine formulation The alcohol phase (developed by E1-1 lipid, DOPE, cholesterol, DMG-PEG2000, and alcohol) and aqueous phases (mRNA sodium citrate solution) were mixed at a proper ratio to prepare the spike-mRNA vaccine. We prepared the RBD-HR vaccine as previously. 16 We mixed MF59-like adjuvant 43 and RBD-HR/trimer protein in equal volumes to form the RBD-HR vaccine. 16 4.5 Immunization and samples collection NIH female mice were randomly divided into four groups, including PBS, homologous mRNA group (mRNA), homologous RBD-HR/trimer group (RBD-HR), and heterologous group (a third RBD-HR/trimer booster following previous priming two doses of mRNA vaccine, mRNA + RBD-HR). Mice were administered according to the homologous or heterologous schedules. The NIH mice were immunized i.m. with a range dose (1, 5, and 10 mg) of mRNA vaccine on days 0 and 21 and immunized i.m. with mRNA or 10 mg RBD-HR vaccine on day 42 after the first vaccination. To test the effects of the RBD-HR vaccine on the immune response for a longer interval after the two doses of mRNA vaccine, we immunized the mice with the third booster on day 111. Blood samples were collected via the eye socket vein on days 56 and 84 and days 125 and 153 and centrifuged at 6000 rpm for 10 min at 4degC. Sera samples were stored at -20degC before use. Seven days after the third-dose immunization, spleens and lymph nodes were harvested. Spleen tissues and lymph nodes were homogenized and single-cell suspensions were prepared with a lymphocyte separation medium. 4.6 Assay of specific antibodies against SARS-CoV-2 RBD RBD-specific antibodies in sera were detected by ELISA. Briefly, recombinant RBD proteins (0.1 mg/well) were coated into 96-well NUNC MaxiSorp plates (Thermo Fisher Scientific, USA) at 4degC for 12 h. Washed the plates with 1x PBST (1x PBS with 0.1% Tween-20) three times and blocked by 1% bovine serum albumin (BSA) at 37degC for 1 h. The plates were incubated with a 1:2 series of diluted sera samples for 1 h at room temperature and then washed three times by 1x PBST. 1:10,000 diluted horseradish peroxidase (HRP)-goat-anti-mouse IgG antibodies were added to the plates and incubated at room temperature for 1 h with five times wash after that. 3,3',5,5'-tetramethyl biphenyl diamine (TMB) was added to the plates and incubated in the dark with 10 min. Stop the reaction by 1 M H2SO4 (100 mL/well) and determine the absorbance at 450 nm. 4.7 Pseudovirus neutralization assay We purchased variants of SARS-CoV-2 pseudoviruses (GFP Luciferase) from Genomeditech Company (China) except BA.3 and BA.4/5 pseudoviruses, which were bought from the Vazyme company (China). NIH mice were intramuscularly injected with mRNA vaccine. After being inactivated at 60degC for 30 min, sera were diluted by a triple-gradient by complete DME medium. And then, diluted sera were incubated with luciferase-expressing pseudovirus (prototypes, B.1.1.7, B.1.351, P.1, B.1.617, C.37, BA.1, BA.2, BA.2.12.1, BA.3, and BA.4/5) at 37degC for 1 h. 1.2 x 104 293T/ACE2 cells were added to each well to express the reporter gene. A period of 48 h later, after removing the infected cell supernatants, 100 mL lysis reagents with luciferase substrate were added to each well. Finally, the plates were detected by a multimode microplate reader (PerkinElmer, USA). 4.8 Blockade of RBD-Fc binding to ACE2 receptor The binding to the ACE2 receptor was measured by RBD-Fc (Omicron) protein. Briefly, RBD-Fc proteins (0.3 mg/mL) were added to sera with serial dilution and incubated at 37degC for 30 min. Then, 293T/ACE2 cells (5 x 104) were added each mixture and incubated at room temperature for 30 min. Cells were washed with BPBS (PBS supplemented with 1% BSA) three times. Then, PE-labeled antihuman IgG-Fc antibodies were added to cells and incubated at 4degC in the dark for 30 min. The binding assay was measured by flow cytometry, and the results were analyzed with NovoCyte Flow Cytometer (ACEA Biosciences). 4.9 Flow cytometry For staining Tfh cells, GC B cells, plasmablast cells, and effect memory T cells, the lymphocytes of the spleens and lymph nodes were stained with CD3(PerCP/Cyanine5.5), CD62L(Brilliant Violet 421), CD4(APC), CD8(FITC), CD69(PE-Cy7), CD44(Brilliant Violet 510), CD95(FITC), B220(PE-Cy7), GL7(PE), CD4(FITC), CD8(Brilliant Violet 510), CD19(Brilliant Violet 421), CD138(APC), CXCR5(APC), PD1(Brilliant Violet 421), and CD19(PE) (all from BioLegend). Cells were stained in the dark at 4degC. A period of 30 min later, cells were washed by 1x PBS and then detected by flow cytometry. For intracellular cytokine staining (ICS), the lymphocytes of the spleens were cultured in a 1640 medium for 72 h. Overall, 10% FBS, 100 mg/mL streptomycin, 100 U/mL penicillin, 1 mM pyruvate (all from Gibco, USA), 50 mM b-mercaptoethanol, and 20 U/mL IL-2 (all from Sigma-Aldrich) were added in the 1640 medium. In addition, we added RBD (10 mg/well) to active cells. To block intracellular cytokine secretion, brefeldin A (BFA, BD Biosciences) were incubated for 6 h before staining. Cells were washed in cold 1x PBS and stained with CD4(Brilliant Violet 421), CD8(FITC), CD44(Brilliant Violet 510), B220(PerCP/Cyanine5.5), and MHC-II(BV711) (all from BioLegend) for 30 min at 4degC. Then cells were fixed and permeabilized to facilitate intracellular staining with anti-IFN-g(PE), anti-IL-4(Brilliant Violet 421), and anti-IL-2(APC) (all from BioLegend) at room temperature for 2 h. Cells were washed by cold 1x PBS and then detected by flow cytometry. 4.10 Statistical analysis GraphPad Prism version 9.1 was used for Statistical analyses. Comparisons among groups were conducted using One-way ANOVA followed by Tukey's multiple comparison post hoc test. p < 0.05 was considered different. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 were used to set statistical significance. AUTHOR CONTRIBUTIONS Xiawei Wei, Xiangrong Song, and Guangwen Lu conceived and supervised the research and designed the experiments. Guangwen Lu, Li Yang, and Jiong Li performed gene cloning, expression, and protein purification. Zhengling Wang and Jinliang Yang performed LC-MS/MS analysis to identify glycosylation sites. Wei Wang, Guobo Shen, Zhiwei Zhao, and Zhenling Wang performed the vaccine formulation. Xiangrong Song prepared MF59-like adjuvant and spike-mRNA vaccine. Dandan Peng, Mingyang Fu, and Tingmei Zhao performed vaccine formulation and vaccination and performed RDB-specific binding antibody assay. Dandan Peng, Cai He, Tingmei Zhao, Jingyun Yang, and Hong Lei performed neutralization of pseudovirus experiment, and measurements of blockade of RBD binding to ACE2 receptor. Dandan Peng, Tingmei Zhao, Li Chen, Wenyan Ren, Yanghong Ni, Aqu Alu, and Jian Liu performed flow cytometry to assay T cell immune response and long-lasting memory responses. Dandan Peng, Mingyang Fu, Weiqi Hong, and Yoshimasa Tanaka analyzed, interpreted the data and assisted with the adjustments of directions and interpretation of the mechanistic aspects of the results Dandan Peng, Mingyang Fu, and Weiqi Hong analyzed, interpreted the data, and wrote the manuscript. All authors have read and approved the final manuscript. CONFLICT OF INTEREST STATEMENT This work was supported by the WestVac Biopharma Co. Ltd. Jiong Li, Wei Wang, Guobo Shen, Zhiwei Zhao, Li Yang, Jinliang Yang, Zhenling Wang, Guangwen Lu, and Xiawei Wei are also working at the WestVac Biopharma Co. Ltd. The remaining authors declare no conflict of interests. ETHICS STATEMENT All animal studies followed and approved by the Institutional Animal Care and Use Committee of Sichuan University (Chengdu, Sichuan, China). ACKNOWLEDGMENTS This work is supported by National Science Foundation for Excellent Young Scholars (32122052) and National Natural Science Foundation Regional Innovation and Development (No. U19A2003). This work was supported by the WestVac Biopharma Co. Ltd. DATA AVAILABILITY STATEMENT All the data are available from the corresponding authors upon reasonable request. |
PMC10000277 | Background Microscopic examination of stool samples can contribute to the early diagnosis of Campylobacter gastroenteritis. However, it is unclear whether the diagnostic performance is reliable when performed by physicians. Methods This prospective study included fresh stool samples collected from patients with gastroenteritis between August 2018 and March 2020. The samples were used for microscopic examination through Gram staining. Two physicians, a clinical laboratory technician, and microbiologists performed the examinations. In addition, antigen tests (QuickNavi-Campylobacter; Denka Co., Ltd.) were evaluated for the samples collected between May 2019 and March 2020. Infection with Campylobacter spp. was confirmed when stool cultures or polymerase chain reaction tests provided positive results. Results Microscopic examination was performed on 205 samples, of which 46 (22.4%) were positive for Campylobacter spp. For the microscopic examination, the sensitivity and specificity were 53.5% and 98.1% for physician A, 46.7% and 96.2% for physician B, 63.0% and 100% for the clinical laboratory technician, and 67.4% and 100% for microbiologists, respectively. The antigen testing was evaluated in 131 of the 205 samples and showed a sensitivity of 93.3% and specificity of 99.0%. Conclusions Microscopic examination of the stool samples showed high specificity. The sensitivity when the examinations were performed by the physicians was insufficient. The rapid antigen tests can reliably detect Campylobacter spp. in stool samples. Microscopic examination of stool samples demonstrated high specificity. However, the sensitivity was insufficient and varied among examiners depending on their experiences. On the other hand, a rapid antigen tests can reliably detect Campylobacter spp. in stool samples. antigen testing Campylobacter infection gastroenteritis Gram staining microscopic examination sensitivity and specificity source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Hirose Y , Akashi Y , Sun Y , Notake S , Ueda A , Kato D , et al. Diagnostic performance of microscopic stool examination in Campylobacter infection performed by different medical specialties. J Gen Fam Med. 2023;24 :102-109. 10.1002/jgf2.596 pmc1 INTRODUCTION Campylobacter spp. are a common cause of bacterial gastroenteritis, 1 most of which are self-limiting. 2 Nevertheless, early diagnosis is desirable, as early antimicrobial treatment is recommended for severely ill patients and those at risk of serious complications. 1 Stool culture is generally performed for detecting Campylobacter spp. in clinical practice, but it is time-consuming. 3 , 4 Therefore, microscopic examinations of fresh stool samples are often performed concurrently and may contribute to early diagnosis. 5 Microscopic examinations performed by microbiologists demonstrated modest sensitivity and high specificity compared to stool cultures. 6 , 7 , 8 In Japan, both laboratory technicians and physicians perform microscopic examinations as point-of-care testing (POCT), especially in teaching hospitals. 5 , 9 However, previous studies have not evaluated its diagnostic performance when conducted by nonmicrobiologists. 6 , 8 Another potent POCT is the rapid antigen testing of stool samples but only a few products are commercially available. 3 , 10 QuickNavi-Campylobacter (Denka Co., Ltd.) is a lateral-flow-type antigen testing with a sensitivity of 75.6% and specificity of 98.6% in patients with enteritis. 10 Nevertheless, the evidence on its validity in diagnostic performance has been insufficient, warranting further research to evaluate its clinical utility. This study aimed to assess the diagnostic performance of microscopic examinations with Gram staining and to compare the results when performed by physicians and microbiologists. In addition, we compared the diagnostic performance of microscopic examination with that of rapid antigen testing using the same stool samples. We employed both stool culture and polymerase chain reaction (PCR) as references. 2 METHODS 2.1 Study design and setting This observational study was conducted at Tsukuba Medical Center Hospital (TMCH) between August 1, 2018 and March 31, 2020. This study first evaluated the clinical performance of direct microscopic examination (August 1, 2018 to April 30, 2019) and conducted the evaluation of antigen testing in addition to the direct microscopic examination from May 1, 2019, onwards. We prospectively enrolled fresh stool samples that were provided for stool culture in daily clinical practice. Patients were asked to self-collect stool samples in plastic containers that were immediately sent to a microbiological laboratory at TMCH, and Gram staining and antigen testing were performed within 24 h. Direct microscopic examinations were performed for Gram-stained samples within 96 h. The current observational study used an opt-out consent procedure and was approved by the ethics committee of TMCH (approval number: 2021-020). Each patient data was anonymized before conducting data analysis. 2.2 Patient enrolment and data collection This study included outpatients and inpatients (within 72 h of hospitalization) suspected of having infectious gastroenteritis. The exclusion criteria were (i) patients who did not suffer from infectious gastroenteritis, (ii) where residual samples were not available, (iii) patients who opted out of participation in the study, and (iv) duplicate cases. We collected the patients' clinical information retrospectively from their medical records. The collected clinical information included age, sex, comorbidities, symptoms (fever, chills, diarrhea, hematochezia, vomiting, abdominal pain, and myalgia/arthralgia), and preceding antibiotic use. 2.3 Procedures for microscopic examinations and antigen testing Both direct microscopic examination and antigen testing utilized fresh stool samples within 24 h of sample submission. For microscopic examination, smeared samples were Gram-stained with Bartholomew and Mittwer-modified reagents (Muto Pure Chemicals Co. Ltd.). The smeared samples were anonymized by study numbers, kept in a storage box, and thereafter were observed at 1000x magnification. Microscopic examinations were performed by two physicians (Physician A [Board certified family medicine and geriatric medicine physician] and Physician B [Board-certified emergency physician] with 16-year and 10-year physician experience, respectively, as at the study initiation), a clinical laboratory technician, and microbiologists. We independently checked and recorded the presence or absence of spiral-shaped Gram-negative rods. Clinical information had not been reviewed at the time of microscopic examination. Antigen testing was performed in accordance with the manufacturer's instructions. In brief, samples were dispensed into the extraction solution and added into the kit wells. Similar to other lateral flow antigen tests, the test was considered positive for Campylobacter spp. if a positive test line appeared. 2.4 Procedures for stool culture Stool samples were incubated micro-aerobically on Campylobacter agar with 5% antimicrobics and 10% sheep blood (Becton, Dickinson and Company, Ltd.) using GasPack method for 48 h at 35degC. After 48-h incubation, translucent drop-like colonies were selected and examined microscopically. Campylobacter spp. were considered positive on stool culture when microscopic examination of the colonies revealed spiral-curved Gram-negative rods. 2.5 Procedures for PCR After being used for microscopic examination, antigen testing, and culture, the residual stool samples were stored at -80degC. The samples were sent to Denka Co. Ltd. for PCR examination if the stool cultures were negative for Campylobacter spp. Frozen stool samples were thawed, and DNA was extracted and purified using the QIAGEN QIAamp DNA Stool Kit (QIAGEN. N.V.). The extracted samples were subjected to real-time PCR using the CycleavePCR Campylobacter (jejuni/coli) Typing Kit (Takara Bio Inc.). The PCR was performed following the manufacturer's instructions: initial denaturation at 95degC for 3 s, followed by 45 cycles of 95degC for 5 s, 55degC for 10 s, and 72degC for 20 s. As an additional analysis, a multiplex PCR system, FilmArray Gastrointestinal (GI) Panel (Biofire Diagnostics, Inc.), was used if samples tested positive for the antigen testing but negative for the culture and PCR examinations. 2.6 Statistical analyses The sensitivity and specificity of microscopic examination and antigen testing were calculated based on the combined results of stool culture and PCR. The 95% confidence intervals were determined by using Clopper and Pearson intervals. In addition, we divided the study period into early and late periods according to the order of sample submission, where each study period contained the same sample size. The sensitivity and specificity of microscopic examinations were compared between the periods. Cohen's and Fleiss' Kappa indices were determined to evaluate the agreement of the microscopic examinations between different examiners. Categorical variables were compared using Fisher's exact test. p Values <0.05 were considered statistically significant. Variables of clinical symptoms that were statistically significant in the univariate analysis were included in a multivariate logistic regression analysis. Cases with missing data were omitted from the analyses. All statistical analyses were conducted using R version 4.1.2. (R Foundation for Statistical Computing). 3 RESULTS Two hundred and ninety-four submitted stool culture specimens were consecutively included. Of these, 13 patients who were determined to have no apparent gastroenteritis (e.g., based on screening on admission) were removed, and 281 patients were screened in this study. Of these 281, we excluded 76 patients: 44 for unavailability of residual samples; four for Gram staining to microscopic examination >96 h; 21 for Gram staining >24 h; three for sample collection >72 h after admission; two for duplication; two for not undergoing a microscopic examination. Finally, we included 205 patients for the evaluation of direct microscopic examinations . Stool culture was positive for Campylobacter spp. in 44 patients, and PCR testing provided additional two positive patients; thus, 46 (22.4%) were considered positive for Campylobacter spp. FIGURE 1 Flowchart showing patient selection 3.1 Demographic data of included patients Patient demographic data are summarized in Table 1. The median age was 23.0 years (interquartile range [IQR]:8.0-40.0), and 94 (45.9%) of patients were female. Comorbidities existed in 23 (11.2%) patients and included seven (3.4%) patients with cerebrovascular disease, six (2.9%) with diabetes mellitus, and four (2.0%) with dementia. Prior to the sample collection, antibiotics had been prescribed for 27 (13.2%) patients. TABLE 1 Demographic data of the study population and cases identified with Campylobacter infection. Variable Campylobacter spp. p-Value Total Positive Negative n = 205 (100%) n = 46 (22.4%) n = 159 (77.6%) Age [IQR] 23.0 [8.0, 40.0] 24.0 [20.3, 28.8] 23.0 [6.0, 44.0] 0.77 Sex (Female) (%) 94 (45.9) 23 (50.0) 71 (44.7) 0.61 Comorbidities (%) 23 (11.2) 2 (4.3) 21 (13.1) 0.50 Immunosuppressive state 2 (1.0) 1 (2.2) 1 (0.6) -- Rheumatic disease 2 (1.0) 1 (2.2) 1 (0.6) -- Any malignancy 4 (2.0) 0 (0.0) 4 (2.5) -- Diabetes mellitus 6 (2.9) 0 (0.0) 6 (3.8) -- Cerebrovascular disease 7 (3.4) 0 (0.0) 7 (4.4) -- Dementia 4 (2.0) 0 (0.0) 4 (2.5) -- Myocardial infarction 1 (0.5) 0 (0.0) 1 (0.6) -- Congestive heart failure 2 (1.0) 0 (0.0) 2 (1.3) -- Chronic pulmonary disease 1 (0.5) 0 (0.0) 1 (0.6) -- Liver cirrhosis 1 (0.5) 0 (0.0) 1 (0.6) -- Prior antimicrobial therapy (%) 27 (13.2) 6 (13.0) 21 (13.2) 1 Bristol scale (median [IQR]) 5.0 [5.0, 6.0] 6.0 [5.0, 7.0] 5.0 [4.0, 6.0] 0.002 Bristol >=6 (%) 97 (47.3) 30 (65.2) 67 (42.1) 0.007 Symptoms (%) Abdominal pain 128 (62.4) 43 (93.5) 85 (53.5) <0.001 Vomiting 74 (36.1) 5 (10.9) 69 (43.4) <0.001 Diarrhea 171 (83.4) 45 (97.8) 126 (79.2) 0.001 Hematochezia 54 (34.2) 12 (28.6) 42 (36.2) 0.45 Fever (>37.8degC) 78 (38.0) 32 (69.6) 46 (28.9) <0.001 Myalgia or arthralgia 19 (9.3) 8 (17.4) 11 (6.9) 0.04 Chills 17 (8.3) 13 (28.3) 4 (2.5) <0.001 Abbreviation: IQR, interquartile range. 3.2 Clinical characteristics of patients infected with Campylobacter spp. Patients with Campylobacter spp. infections were more likely to have diarrhea (97.8% vs. 79.2%, p = 0.001), abdominal pain (93.5% vs. 53.5%, p < 0.001), fever (69.6% vs. 28.9%, p < 0.001), and chills (28.3% vs. 2.5%, p < 0.001) than non-infected patients, but vomiting was less frequent (10.9% vs. 43.4%, p < 0.001; Table 1). Multivariate analysis revealed that abdominal pain, vomiting, fever, and chills were significantly associated with Campylobacter infections (Table 2). The multivariate odds ratios (OR) for each variable were as follows: abdominal pain, OR 13.7 (95% CI: 3.65-51.7); vomiting, OR 0.18 (95% CI: 0.06-0.55); fever, OR 6.14 (95% CI: 2.43-15.5); and chills, OR 6.50 (95% CI: 1.23-34.3). TABLE 2 Odds ratios (with 95% confidence intervals) of clinical symptoms for Campylobacter infection. Symptoms Crude OR (95%CI) p-Value Adjusted OR (95%CI) p-Value Abdominal pain 12.4 (3.71-64.9) <0.001 13.7 (3.65-51.7) <0.001 Vomiting 0.16 (0.05-0.44) <0.001 0.18 (0.06-0.55) 0.002 Diarrhea 11.7 (1.84-488.9) 0.001 8.31 (0.98-70.76) 0.05 Hematochezia 0.71 (0.30-1.60) 0.45 -- -- Fever (>37.8degC) 5.56 (2.61-12.4) <0.001 6.14 (2.43-15.5) <0.001 Myalgia or arthralgia 2.81 (0.92-8.32) 0.04 0.61 (0.14-2.7) 0.52 Chills 15.0 (4.28-67.1) <0.001 6.50 (1.23-34.3) 0.03 Note: Variables of p < 0.05 in univariate analyses were included in the multivariate analysis. The 95% confidence intervals are shown in parentheses. Abbreviations: CI, confidence interval; OR, odds ratio. 3.3 Diagnostic performance of microscopic examinations The results of the microscopic examination are described in Table 3. Microbiologists showed the highest sensitivity of 67.4% and specificity of 100% for detection of Campylobacter spp. Although the sensitivity was 53.5% for physician A and 46.7% for physician B, the specificities exceeded 90% for all examiners. TABLE 3 Diagnostic performance of microscopic examinations by each examiner and rapid antigen test Examiner/test Sensitivity, % (95% CI) Specificity, % (95% CI) PPV, % (95% CI) NPV, % (95% CI) Physician A 53.5 (37.7-68.8) 98.1 (94.4-99.6) 88.5 (69.8-97.6) 88.3 (82.5-92.7) Physician B 46.7 (31.7-62.1) 96.2 (91.9-98.6) 77.8 (57.7-91.4) 86.2 (80.2-91.0) Clinical laboratory technician 63.0 (47.5-76.8) 100 (97.7-100) 100 (88.1-100) 90.2 (84.8-94.2) Microbiologists 67.4 (52.0-80.5) 100 (97.7-100) 100 (88.8-100) 91.4 (86.2-95.1) Rapid antigen test a 93.3 (77.9-99.2) 99.0 (94.6-100) 96.6 (82.2-99.9) 98.1 (93.2-99.8) Note: Sensitivity, specificity, positive predictive value, and negative predictive value are provided with 95% confidence intervals. Abbreviations: CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value. a The diagnostic performances of rapid antigen test were evaluated using a subpopulation of 131 cases. All examiners demonstrated an increased sensitivity during the later study period (Table 4). The sensitivities in the early (n = 102) and late (n = 103) study periods were 50.0% and 57.9% for the physician A, 34.6% and 63.2% for the physician B, 59.3% and 68.4% for the laboratory technician, and 63.0% and 73.7% for microbiologists, respectively. TABLE 4 Diagnostic performances of microscopic examinations in the early and late period of the study. a Sensitivity, % (95% CI) Specificity, % (95% CI) Examiner Early study period Late study period Early study period Late study period Physician A 50.0 (29.1-70.9) 57.9 (33.5-79.7) 100 (95.0-100) 96.3 (89.7-99.2) Physician B 34.6 (17.2-55.7) 63.2 (38.4-83.7) 97.3 (90.6-99.7) 95.1 (88.0-98.7) Clinical laboratory technician 59.3 (38.8-77.6) 68.4 (43.4-87.4) 100 (95.2-100) 100 (95.7-100) Microbiologists 63.0 (42.4-80.6) 73.7 (48.8-90.9) 100 (95.2-100) 100 (95.7-100) Note: Each study period would contain the same sample size (early, n = 102; late, n = 103). Abbreviation: CI, confidence interval. a The study period was divided into early and late periods according to the order of sample submission. The Fleiss' kappa value among all examiners for all samples was 0.68, while Cohen's kappa ranged from 0.51 to 0.89 . The agreement between the clinical laboratory technician and microbiologists was the highest, and that between the two physicians was the lowest. 3.4 Diagnostic performance of antigen testing Stool samples from 131 patients including 30 positive cases were subjected to both antigen testing and microscopic examination. The rapid antigen testing showed a sensitivity of 93.3% and specificity of 99.0% (Table 3). There were two false negative, one false positive, and one invalid results. For the sample with a false positive result, an additional FilmArray assay detected Campylobacter spp. The two stool samples with false negative results did not contain solid pieces (Bristol scale 7) and grew a few colonies of Campylobacter spp. on the medium. When evaluating the same stool samples, the sensitivity of antigen testing was higher than that of microscopic examination by all examiners (Table S1). 4 DISCUSSION This prospective study showed that the sensitivity of microscopic examinations was not sufficient for detecting Campylobacter spp., regardless of the examiner. The sensitivity was low especially when physicians performed the examination, although the specificity of all examiners exceeded 90%. Compared with microscopic examinations, the rapid antigen test showed higher diagnostic performance. Our study revealed the test performance of the microscopic examination was comparable with previous studies which reported the sensitivities of 43.5%-65.5% and specificities of 88.0%-99.4%. 6 , 8 , 11 Microscopic examinations performed by physicians were less sensitive than those performed by laboratory technician and microbiologists. In addition, the laboratory technician and microbiologists showed high agreement (Cohen's kappa = 0.90), whereas physicians showed the least agreement (Cohen's kappa = 0.511). 12 Physicians do not regularly perform microscopic examinations. Wang et al. 7 reported that the inexperience of a microscopist may cause false negative test results. In this study, all examiners' sensitivity improved in the later period compared to that in the early period. Even for inexperienced physicians, the sensitivity of the examination can be improved through experience and training. Campylobacter infection was significantly associated with abdominal pain, vomiting, fever, and chills (Table 2). Consistent with our study, previous studies reported that vomiting was less frequent in Campylobacter infection, 13 while fever and diarrhea were more common 3 , 8 . Gillespie et al. 14 showed that vomiting was more likely to occur in younger children, although no association between vomiting and age was observed in this study. Vomiting usually occurs in toxin-producing (e.g., Staphylococcus aureus and Bacillus cereus) and small-intestinal types of infectious gastroenteritis. Campylobacter spp. generally affects the large intestine, which may result in a lower frequency of vomiting or nausea. Another useful clinical manifestation is the presence of polymorphonuclear leukocytes (PMNL) in stools. The presence of PMNL indicates an inflammation of the bowels in Campylobacter gastroenteritis 15 ; however, it was not examined in our study. These clinical features may help to suspect Campylobacter spp. as the causative microorganism of acute gastroenteritis. The rapid antigen test, QuickNavi-Campylobacter, demonstrated favorable sensitivity and specificity results. The sensitivity of the antigen test was better than that of microscopic examination for the same stool samples. Regarding the two samples with false negative results in the antigen test, a small number of colonies were detected in culture. We believe that the low bacterial load in the samples led to false negative results. As for the specificity, one false positive case was confirmed to be Campylobacter spp. positive by further evaluation using the FilmArray assay. 16 In this study, the antigen testing gave positive results only when Campylobacter spp. truly existed in samples. In addition to favorable diagnostic performance, antigen testing can provide results in a short time, which may help early diagnosis and proper management in patients with gastroenteritis. Several multiplex molecular assays have been developed and used in clinical settings for other types of POCT. These systems can detect multiple pathogens with high sensitivity 16 , 17 and are beneficial for vulnerable individuals, such as hospitalized or immunocompromised patients. 18 Appropriate use of each type of POCT is crucial, in different clinical settings. Microscopic examinations and antigen testing can be performed in primary care facilities due to the short turnaround time, easy procedure, and the unnecessity of special equipment. Nevertheless, our study indicated that microscopic examinations by physicians could not reliably rule out Campylobacter infection. Antigen testing showed higher sensitivity than microscopic examinations, and the interpretation of the test results can be more objective, although evaluated only in a small study population 10 , 19 and not commercially available. Multiplex molecular assays have demonstrated excellent diagnostic performance 16 , 17 ; however, the requirement of special equipment and expensive examination cost can limit their clinical usefulness. Given that most patients with gastroenteritis suffer mild illnesses in the primary care settings, the use of multiplex molecular assays should be reserved for hospitalized or emergency department patients. The microscopic examinations can contribute to antimicrobial stewardship. 20 An appropriate choice of empiric antimicrobials depends on the assumption of the causative microorganisms. The ability to assume the causative microorganisms can be achieved by microscopic examinations. 20 In addition, the pedagogical effect regarding infectious diseases can be expected when physicians can successfully associate the results of the microscopic examinations with the treatment strategy. 20 The competency for microscopic examinations can be enhanced through lectures, group discussions, and hands-on workshops. Among them, hands-on workshops showed the highest education effect. 21 Our study also indicated that the experience acquired by performing microscopic examinations contributed to improving its sensitivity. Besides, an appropriate feedback increases the efficacy of the educational process. 22 The practitioner can be effectively trained by a well-experienced examiner for microscopic examinations, for example, those with a license in performing microbiological examinations and those with a sensitivity of over 60% in performing microscopic examinations. 6 , 8 , 11 To maximize the educational effect, we suggest that the residency training program should start with hands-on workshops during orientation and that the residents should perform microscopic examination while receiving continual feedback. Regular conferences, focused on microscopic examination, are also effective in improving competency. This study had some limitations. First, we used frozen samples for the PCR examination. Therefore, the frozen storage process may have affected the PCR results. 23 Second, the stool culture and PCR methods used in this study could not distinguish between the species of Campylobacter. The examination results and clinical manifestations may possibly differ among Campylobacter species. Third, a few examiners performed microscopic examinations, and data on patients' symptoms were not prospectively collected from their medical records. Therefore, further studies are needed to validate the generalizability of our results. 5 CONCLUSIONS Microscopic examination of stool samples demonstrated high specificity when using the combined results of culture and PCR as references. However, the sensitivity was insufficient when the examinations were performed by the physicians. Microscopic examinations by well-trained examiners and the use of rapid detection tests can reliably detect Campylobacter spp. AUTHOR CONTRIBUTIONS Y. H. collected data, produced figures, and drafted the manuscript. Y. A. planned the study, collected data, constructed the database, and analyzed the data. D. K. performed the PCR analysis for Campylobacter spp. H. S. supervised the study. All the authors contributed to the preparation of the manuscript and met the criteria endorsed by the International Committee of Medical Journal Editors (ICMJE). CONFLICT OF INTEREST Denka Co., Ltd. provided free antigen test kits for this study and performed the PCR examinations. H.S. received lecture fees from Denka. Co. Ltd. D. K. and S. M. belong to Denka Co., Ltd. ETHICAL APPROVAL AND PATIENT CONSENT This study used an opt-out consent procedure and was approved by the ethics committee of TMCH (approval number: 2021-020). CLINICAL TRIAL REGISTRATION The study protocol was registered on UMIN-CTR (UMIN000038341). Supporting information Figure S1. Click here for additional data file. Table S1. Click here for additional data file. ACKNOWLEDGMENTS We thank Yoko Ueda and the staff at Tsukuba Medical Center Hospital for their intensive support in this study. |
PMC10000278 | Background Despite the increasing need for primary care physicians (PCPs) around the world, few physicians choose it as a career. PCPs who can find meaning and enjoyment in their work can be role models for medical students and professionals, which may encourage more physicians to specialize in primary care. We aimed to compare the kinds of work that Japanese PCPs who derive greater positive meaning from work engage in versus those who derive less positive meaning from work. Methods This was a cross-sectional study that used self-administered questionnaires to ask Japanese PCPs about their basic characteristics and engagement in and enthusiasm for various types of work. The outcomes of the Japanese version of the work as meaning inventory (J-WAMI) were also assessed. Participants were divided into low-scoring groups according to the median J-WAMI score, and logistic regression analysis was performed to identify factors related to the high J-WAMI-scoring group. Results A total of 268 out of 330 participants were included in the analysis. Males comprised 74.3%, and participants' average experience as a physician was 20.2 years. The median overall J-WAMI score was 38. Factors associated with the high J-WAMI scoring group were enthusiasm for outpatient care (OR: 1.04, 95% CI: 1.02-1.06) and engagement in research (OR: 2.74, 95% CI 1.33-5.66). Conclusions Enthusiasm for outpatient care and engagement in research are associated with greater positive meaning of work among PCPs. Supporting these types of work may enhance PCPs' value of their work. Enthusiasm for outpatient care and engagement in research are associated with greater positive meaning of work among primary care physicians in Japan. family medicine research JSPS KAKENHI21K10297 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Yamamoto Y , Haruta J , Goto R , Maeno T . What kinds of work do Japanese primary care physicians who derive greater positive meaning from work engage in? A cross-sectional study. J Gen Fam Med. 2023;24 :94-101. 10.1002/jgf2.595 pmc1 INTRODUCTION Increasingly complex medical needs such as chronic diseases caused by aging, changing lifestyles, and diseases related to mental health highlight the importance of primary care around the world. 1 In Japan, as in other countries, there is a rising need for primary care physicians (PCPs) who can provide more comprehensive and continuous care, as opposed to that offered through the limited lens of specific organs or diseases. 2 PCPs are known by various names including general practitioners (GP) and family physicians (FP) in Japan. In this paper, we refer to them as PCPs. To meet the increasing need for primary care, there has been a recent move towards training specialists as GP/FP. Unlike in Western countries, there was no system for certifying GP or FP in Japan for a long time; instead, organ-specific specialists provided primary care. 3 However, in 2010, the Japan Primary Care Association (JPCA) began certifying primary care specialists, and its training system obtained international certification from the World Organization of Family Doctors (WONCA) in 2020. 4 In the intervening period, the Japanese Medical Specialty Board established a new specialist system in 2018. 3 Today, it is difficult to determine the exact number of Japanese PCPs because of the characteristics of Japanese primary care, such as the fact that organ-specific specialists provide primary care and that primary care is provided in both clinics and the outpatient departments of medium-sized hospitals. Available statistics indicate that there are 1067 JPCA-certified family physicians, and 5349 with diplomas in primary care from JPCA (as of February 2022), 5 and that 102,457 physicians work in clinics. 3 As mentioned above, a training system for primary care is gradually being established, 3 however, PCPs remain insufficiently recognized among medical professionals and medical students, and few physicians choose to specialize in primary care. 6 There are several barriers and promoters for residents choosing primary care as a career. Barriers include a lack of local role models, anxiety related to dealing with diverse and broad areas, and uncertainty about the future. 7 These barriers are thought to be linked to a lack of recognition of primary care by society and other departments, and few opportunities to meet PCP role models. 7 , 8 In particular, during clinical clerkships at university and in training before choosing a specialty, medical students rarely see PCPs active in the community, including in actual outpatient care or community activities, which may prevent them from realizing the attractiveness of primary care medicine. 7 On the other hand, positive exposure to PCPs working in the field is an important promoter for the recruitment of students and residents. 9 Additionally, when physicians enjoy and are satisfied with their work, this triggers the interests of medical students in the same field and has a significant impact on students' career choices. 10 Medical students have been shown to be inspired by their role models to choose specialties they might not otherwise have considered. 10 Thus, PCPs who enjoy their work may become role models for medical professionals and students, thereby increasing recognition of primary care and the number of physicians who specialize in primary care. 8 , 9 , 10 One factor associated with enjoying and being satisfied in one's work is meaning of work (MW). The concept of MW has evolved in the career, management and psychological fields since the 1980 s. 11 Although MW has a variety of definitions, we have adopted the original definition of "the central importance of work for people". 12 Several studies have found moderate or higher correlations between job satisfaction and MW, indicating that these concepts are closely related. 13 , 14 MW is also correlated with work engagement, commitment, life satisfaction, meaning of life, and general health measures. 13 Thus, finding MW can lead to being satisfied with, enjoying and feeling enthusiastic about work, and greater general well-being. Reports from outside Japan indicate that PCPs consider diagnosing and treating common diseases, following-up on chronic diseases, and managing risk conditions to be meaning tasks. 15 , 16 However, there is little other research on MW among PCPs. The purpose of this study was to compare the kinds of work that Japanese PCPs who derive greater positive meaning from work engage in versus those who derive less positive meaning from their work. This information may help PCPs find opportunities to develop meaning, enjoyment and satisfaction in their work. 2 METHODS 2.1 Design and participants We conducted a cross sectional online study using self-administered questionnaires. Based on the purpose of this study, participants were physicians who were members of JPCA, the largest academic organization related to primary care in Japan. Many physicians in the JPCA serve as role models for medical students and residents. Inclusion of JPCA members assumes that they agree with the principles of primary care regardless of the participants' original specialty. The exclusion criteria were junior residents defined as physicians, who graduated less than 2 years prior, and physicians who did not complete the questionnaire. We recruited participants through the JPCA mailing list from January 9 to February 12, 2021. The first page of the questionnaire provided a short description of the background and purpose of this study. Participants were informed that submission of the anonymous questionnaire implied that they were providing consent for participation. To calculate the required sample size, we considered that we would conduct a logistic regression analysis using around 10 independent variables, based on previous studies. 15 , 16 , 17 , 18 There would be dependent variables stratified by the median of the outcome values described below, and we assumed that the number of participants in each group would be similar. As at least ten participants per independent variable were required for each group, 19 the sample size was calculated to be one hundred per each group, or two hundred overall. 2.2 Measures The questionnaires inquired about the following participant characteristics: gender, number of years of experience as a physician, family structure (whether or not they live with a partner or children), whether or not they are JPCA-certified family physicians, the size of the city where the physician works (large city with a population of 500,000 or more; medium city with a population of 100,000 to 300,000; small city with a population of around 50,000; village; and remote island and remote area), type of facility in which the physician works (clinic or hospital), and acceptance of students and residents for educational purposes at the facility where the physician works. The outcome of this study, MW, was assessed using the Japanese version of The Work as Meaning Inventory (J-WAMI). WAMI was developed by Steger et al. in 2012 to measure MW among individuals (Appendix S1). 20 The scale theoretically explores the elements of MW, defining it through three subscales: positive meaning (PM); meaning-making through work (MM); and greater good motivation (GG). Example items include "I have found a meaningful career" (PM), "I view my work as contributing to my personal growth" (MM), and "The work I do serves a greater purpose" (GG). The questionnaire contains 10 items. Each question is answered on a 5-point Likert Scale, with 1 point indicating "absolutely untrue" and 5 points indicating "absolutely true". Urata et al. developed J-WAMI in 2019, and confirmed its reliability and validity. 21 In this study, higher J-WAMI scores were operationally defined as feeling more positive meaning of work. The questionnaires also inquired about whether or not the participant had been engaged in clinical practice (outpatient care, home visit care, inpatient care, and emergency care), education, research, community activities, and meetings and management in the past year. We used engagement in each type of work as an objective indicator in the analysis. The participants were also asked to rate their enthusiasm for clinical practice (outpatient care, home visit care, inpatient care, emergency care), education, research, community activities, and meetings and management from 0 to 100 on a visual analog scale. For jobs in which they were not currently engaged, the participants were asked how enthusiastic they would be about becoming engaged in each job if they had the opportunity to do so in the future. Physicians' enthusiasm for each type of work was used as a subjective index in the analysis. 2.3 Data analysis J-WAMI scores are presented as median and interquartile range (IQR), while other continuous variables are presented as mean and standard deviation (SD). To identify the characteristics of those with high J-WAMI scores, participants were divided into high and low J-WAMI scoring groups based on a cutoff. Given the paucity of related studies, we used the median, or mean, as the cutoff. In univariate analysis, differences between the two groups were analyzed using a t-test for continuous variables and chi-squared test or Fisher's exact test for categorical variables. Variables found to be moderately associated with the high-scoring group (p < 0.1) were further analyzed using logistic regression analysis. Gender and years of experience as a physician were added as independent variables to those found to be significantly correlated with the high-scoring group in the univariate analysis. p < 0.05 was used for tests of statistical significance. In this study, we performed a complete case analysis. All analyses were performed using SPSS version 27 (IBM). Our study matched the STROBE criteria (Appendix S2). 2.4 Ethical considerations This study was conducted with the approval of the Medical Ethics Committee of the University of Tsukuba (approval number. 1601). 3 RESULTS 3.1 Descriptive statistics After two additional reminders and confirmation that the number of responses had reached the expected sample size, recruitment was closed. At the time the study was conducted, there were approximately 5500 physician members on the JPCA mailing list. Of the 330 participants who viewed the questionnaires, 268 physicians who agreed to participate and answered all questions were included in the analysis . Of the 268 physicians, 199 indicated they were male (74.3%), one indicated "other" and one did not provide a response. Participants' average experience as a physician was 20.2 years (SD 10.7), and 81 (30.2%) indicated they were JPCA-certified family physicians. A total of 135 physicians (50.4%) reported that they were working in clinics, while one answered "other" (see the "overall" column in Table 1). FIGURE 1 Flow chart of primary care physician participants in the study. Of the 330 participants who viewed the questionnaires, 268 physicians who agreed to participate and answered all questions were included in the analysis. TABLE 1 Basic characteristics of participants and comparison between high and low J-WAMI-scoring groups Overall, n = 268 Low-scoring group <38 points, n = 121 High-scoring group >=38 points, n = 147 p-Value Male, n (%) b 199 (74.3) 88 (72.7) 111 (75.6) 0.538 Years of experience as a physician, years, mean (SD) a 20.2 (10.7) 21.17 (10.0) 19.4 (11.0) 0.167 Family structure (including duplicates) Living with a partner, n (%) b 217 (81.0) 96 (79.3) 121 (82.3) 0.537 Living with children, n (%) b 157 (58.6) 63 (52.1) 94 (63.9) 0.049 JPCA-certified family physician, n (%) b 81 (30.2) 36 (29.8) 45 (30.6) 0.879 Size of the city where the physician works Small city or smaller, n (%) b 96 (35.8) 44 (36.3) 52 (35.6) 0.866 Medium-sized city or larger, n (%) b 172 (64.2) 77 (63.6) 95 (64.6) Type of facility in which the physician works Clinic, n (%) b 135 (50.4) 60 (49.6) 75 (51.0) 0.772 Hospital, n (%) b 132 (49.3) 61 (50.4) 71 (48.3) Acceptance of students, residents for educational purposes at the facility where the physician works, n (%) b 199 (74.3) 90 (74.3) 109 (74.1) 0.966 Abbreviations: JPCA, Japan Primary Care Association; J-WAMI, Japanese version of the work as meaning inventory; SD, standard deviation. a t-Test. b Chi-squared test. Because the total J-WAMI score was not normally distributed in this study, participants were divided into two groups based on the median J-WAMI score (38 points [IQR 34-41]): those with >=38 points formed the high-scoring group, and those with <38 points formed the low-scoring group. The median J-WAMI score was 41 [IQR 39-44] for the high-scoring group (n = 147), and 34 [IQR 30-36] for the low-scoring group (n = 121) (Table 2). Among the scale items, only item 2, "I view my work as contributing to my personal growth," showed a ceiling effect. TABLE 2 Total J-WAMI score, engagement in and enthusiasm for different types of work and comparison between low-scoring groups Overall, n = 268 Low-scoring group <38 points, n = 121 High-scoring group >=38 points, n = 147 p-Value Total J-WAMI score a , median (IQR) b 38 (34-41) 34 (30-36) 41 (39-44) <0.001 Subscale score c Positive meaning, median (IQR) b 16 (14-17) 14 (12-15) 17 (16-19) <0.001 Meaning-Making Through Work, median (IQR) b 12 (11-13) 10 (8-11) 13 (12-14) <0.001 Greater Good Motivations, median (IQR) b 10 (9-12) 9 (7-10) 12 (11-12) 0.003 Engagement in each type of work (reference: no) Outpatient care, n (%) d 265 (98.9) 118 (97.5) 147 (100.0) 0.091 Home visit care, n (%) e 190 (70.9) 83 (68.6) 107 (72.8) 0.452 Inpatient care, n (%) e 124 (46.3) 57 (47.1) 67 (45.7) 0.803 Emergency care, n (%) e 130 (48.5) 61 (50.4) 69 (47.0) 0.571 Education, n (%) e 204 (76.1) 82 (67.8) 122 (83.0) 0.004 Research, n (%) e 136 (50.8) 48 (39.7) 88 (59.9) <0.001 Community activities, n (%) e 178 (66.4) 74 (61.2) 104 (70.8) 0.098 Meetings and management, n (%) e 210 (78.4) 88 (72.7) 122 (83.0) 0.042 Enthusiasm for each type of work f Outpatient care, mean (SD) b 77.6 (19.8) 70.6 (22.4) 83.31 (15.1) <0.001 Home visit care, mean (SD) b 67.0 (31.5) 60.3 (31.3) 72.6 (30.6) 0.001 Inpatient care, mean (SD) b 46.8 (35.2) 43.0 (35.9) 49.8 (34.5) 0.119 Emergency care, mean (SD) b 44.8 (32.0) 40.7 (31.5) 48.1 (32.2) 0.058 Education, mean (SD) b 59.5 (30.7) 51.2 (31.1) 66.4 (28.6) <0.001 Research, mean (SD) b 42.2 (33.1) 34.4 (33.1) 48.7 (31.8) <0.001 Community activities, mean (SD) b 59.7 (28.1) 52.5 (28.2) 65.6 (26.7) <0.001 Meetings and management, mean (SD) b 47.3 (29.4) 41.7 (28.9) 51.8 (29.1) 0.005 Abbreviations: IQR, interquartile range; SD, standard deviation. a The maximum total J-WAMI score is 50. b t-Test. c The maximum subscale score in the J-WAMI is 20 points for Positive Meaning, 15 points for Meaning-Making Through Work, and 15 points for Greater Good Motivations. d Fisher's exact test. e Chi-squared test. f Enthusiasm for each type of work was measured from 0 to 100 on a visual analog scale. Regarding the physician's engagement in various types of clinical and nonclinical work in the past year, in terms of clinical work, 265 (98.9%) physicians indicated they were engaged in outpatient care, while 190 (70.9%) physicians conducted home visit care. Among nonclinical work, 136 (50.8%) physicians were engaged in research. Physicians' enthusiasm for clinical work was highest at 77.6 (SD 19.8) for outpatient care, and 67.0 (SD 31.5) for home visit care. In contrast, they indicated lower enthusiasm for emergency care and research at 44.8 (SD 32.0) and 42.2 (SD 33.1), respectively (see the "overall" column in Table 2). 3.2 Comparison of basic characteristics and each measure between low-scoring groups We compared participants' basic characteristics, total J-WAMI score, engagement in each type of work, and enthusiasm for each type work between the low-scoring groups. Because only a small number of respondents answered "other" for gender and type of work facility, they were excluded from the analysis. We confirmed that the high-scoring group had significantly higher total J-WAMI scores than the low-scoring group (p < 0.01). In terms of basic characteristics, the high-scoring group was significantly more likely to live with children (p = 0.049). In terms of engagement in each type of work, the high-scoring group was more likely to be engaged in education, research, community activity and meetings and management (p = 0.091, p = 0.004, p < 0.001, p = 0.098, p = 0.042, respectively). In terms of enthusiasm for each type of work, the high-scoring group was significantly more likely to be enthusiastic about outpatient care, home visit care, emergency care, education, research, community activities, and meetings and management (p < 0.001, p = 0.001, p = 0.058, p < 0.001, p < 0.001, p < 0.001, and p = 0.005, respectively) (see columns for the high-scoring group and low-scoring group in Tables 1 and 2). 3.3 Factors associated with the high-scoring group Based on the logistic regression analysis, the high-scoring group was associated with enthusiasm for outpatient care (odds ratio [OR]: 1.04, 95% confidence interval [CI] 1.02 to 1.06) and engagement in research (OR: 2.85, 95% CI 1.39-5.84) (Table 3). All variance inflation factor values were <2.2, and no obvious multicollinearity was identified. 22 TABLE 3 Results of logistic regression analysis of the factors associated with the high-scoring group OR of high scoring group 95% CI p-Value Years of experience as a physician 0.99 0.96-1.02 0.376 Male (reference: female) 1.59 0.89-2.85 0.115 Living with children (reference: no) 1.43 0.81-2.52 0.219 Engagement in education (reference: no) 1.53 0.73-3.21 0.25 Engagement in research (reference: no) 2.85 1.39-5 0.006 Engagement in community activity (reference: no) 1.31 0.69-2.46 0.409 Engagement in meetings and management (reference: no) 1.29 0.63-2.65 0.625 Enthusiasm for outpatient care a 1.04 1.02-1.06 <0.001 Enthusiasm for home visit care a 1.01 1.00-1.02 0.254 Enthusiasm for emergency care a 0.99 0.99-1.00 0.559 Enthusiasm for education a 1.00 0.99-1.02 0.366 Enthusiasm for research a 1.00 0.99-1.01 0.638 Enthusiasm for community activities a 1.01 0.99-1.02 0.375 Enthusiasm for meetings and management a 1.00 0.99-1.01 0.988 Abbreviations: CI, confidence interval; OR, odds ratio. a Enthusiasm was measured from 0 to 100 on a visual analog scale. 4 DISCUSSION We found that Japanese PCPs who derive greater positive meaning from their work were more enthusiastic about outpatient care and engaged in research. 4.1 Relationship between enthusiasm for outpatient care and meaning of work While few studies have examined MW among PCPs, there are some reports on job satisfaction, rewards, and identity among this profession. Studies on job satisfaction among PCPs report a relationship with variety in clinical practice, successful medical management of patients and the subsequent feeling of being competent, bonds with patients and family members, and passion for the work. 18 , 23 Another study reported that a PCP's identity is linked to a balance in the breadth and depth of clinical practice, patient/family relationships, and the comprehensive nature of patient care. 24 In primary care outpatient settings in Japan, about 90% of PCPs routinely address various health problems, from internal medicine to musculoskeletal and dermatological fields. 17 They also have to cope with multimorbidity, an increasing issue in the aging population, 25 and with complex problems that require a psychosocial approach. 26 Thus, for PCPs, outpatient care may be an area that requires improvisation, which involves creativity, to manage a wide range of ages, problems and disease stages; provide long-term and relational continuity; deal with the complexity and comprehensiveness of the problem. 27 Creativity is one factor that has been found to differ between PCPs and internists in previous studies on factors related to job satisfaction. 28 In other words, primary outpatient care is one area where PCPs can exercise their role by performing the creative work required to address undifferentiated and varied problems in a comprehensive approach. Physicians who are able to enthusiastically engage in outpatient care are likely to have a higher sense of their role as a PCP, and will consequently consider their work more meaningful. In addition, it is easier to observe positive changes in patients after physician interventions in outpatient care, and repeated exposure to such positive changes may enhance physicians' MW. However, there are reports that PCPs who care for patients with multimorbidity are likely to experience burnout. 29 Younger physicians and others with inadequate skills in outpatient care should be mindful of burnout, as it may reduce their enthusiasm for providing outpatient care resulting from the burden of treating highly complex patients. 4.2 Relationship between research engagement and MW Few studies have examined the relationship between research engagement and job satisfaction or other aspects of PCPs' work. Previous studies have noted the low level of research in primary care in Japan. 30 In this study, about half of the physicians responded that they were engaged in research. It is possible that there was selection bias in our study, in that the physician participants may have already had an interest and engagement in research. Our use of a broader definition of the term "research" in this study, which included writing case reports and providing support for conference presentations, may also have led many respondents to indicate they were engaged in research. In this study, almost all of the participants who indicated they routinely conducted research were engaged in outpatient care and were clinician researchers 31 who were engaged in both clinical practice and research. In Japan, physicians are often assigned clinical duties even in research and educational institutions such as universities. Clinician researchers can address emerging and relevant real-world issues that arise in daily practice while accounting for the actual situation in the field, and promote evidence-based practice, thus acting as a bridge between the research and practice worlds. 31 Thus, the participants' research achievements and ability to translate their findings to patients and the community as clinicians may underlie their sense of accomplishment and enhanced MW. Furthermore, research in the primary care field covers a wide range of topics 32 , 33 and aims to solve problems at the individual level as well as the family, social and community levels. 31 , 34 , 35 Thus, PCPs may feel that they are contributing to the community and society more broadly through their research, which may make their work feel more meaningful. 4.3 Impact on future practice and research As this was a cross-sectional study, we could not determine a strict causal relationship between MW and having enthusiasm for outpatient care or being engaged in research. Past studies have reported that work becomes meaningful when people are able to demonstrate competence in an area that they feel is their identity, when they are able to positively impact someone or something other than themselves, when they are challenged and accomplish a task, and when they are doing work that is important to society. 11 Therefore, it is possible that having enthusiasm for outpatient care and being engaged in research can lead PCPs to derive positive meaning from their work through the experiences described above. The finding that enthusiasm for outpatient care is associated with positive MW among PCPs could prompt more active engagement in outpatient care, which tends to be a routine task. Furthermore, the result suggests that developing support strategies to encourage engagement in outpatient care may also be important. PCPs who are enthusiastic about outpatient care can also be role models to medical students and residents, and improving education for residents who find outpatient care burdensome may help enhance the careers of PCPs. In addition, for those interested in research, an environment that allows them to focus on research or a structure that facilitates participation in research from their residency may extend their engagement in this type of work. 36 While most previous studies have been concerned with investigating factors that have a positive impact on MW, recent work has increasingly focused on the negative aspects of MW. 14 Future research that also examines factors that reduce MW, such as burnout, which is a common occurrence in PCPs, 37 may offer important insights. 4.4 Limitations There were several limitations in this study. First, while WAMI has been used in some studies on PCPs, it has not been validated in healthcare settings or among PCPs. Therefore, the concept assessed by WAMI may not be fully compatible with Japanese PCPs. However, this questionnaire incorporates the abstract concept of MW into 10 concrete questions and could be useful in future research once validated. Further research is also needed to determine the optimal way to set cutoff values for the J-WAMI score using a larger sample size and range of participants. Second, because we conducted a web-based study, there may have been selection bias in that respondents may have already had a strong interest in the topic of this survey and high baseline MW. Additional research using tools other than web-based surveys is needed to confirm our findings. Third, not all Japanese PCPs are members of the JPCA. However, as we conducted this study with the intention of applying the findings to future specialty training programs, we chose to focus on JPCA members to include physicians who have received specialty training and are currently supervising physicians. Fourth, past studies have shown that MW is negatively associated with depression and anxiety. Because we did not assess these symptoms, the impact of depression and anxiety on MW should be more comprehensively assessed in the future. Fifth, caution is needed when generalizing the results because of the unique context of primary care in Japan. However, the results may be adaptable to Asian countries where primary care is still a developing field. 38 Furthermore, given the scarcity of research on primary care worldwide, we believe our findings may provide useful background or a means for comparison in research in other countries. 5 CONCLUSION Enthusiasm for outpatient care and engagement in research are associated with positive MW among PCPs. Supporting outpatient care, where PCPs can better exercise their identity, and research in the primary care field, which can serve as a bridge to the clinical world, may contribute to positive values like satisfaction and enjoyment among physicians through enhancing MW. FUNDING INFORMATION This work was supported by JSPS KAKENHI Grant Number 21K10297. CONFLICT OF INTEREST The authors have stated explicitly that there are no conflicts of interest in connection with this article. ETHICS APPROVAL This research has been approved by the Ethics Committee of the University of Tsukuba (approval number: 1601). PATIENT CONSENT STATEMENT All study participants agreed to participate in this study. CLINICAL TRIAL REGISTRATION None. Supporting information Appendix S1 Click here for additional data file. Appendix S2 Click here for additional data file. DATA AVAILABILITY STATEMENT The data underlying this article will be shared on reasonable request to the corresponding author. |
PMC10000279 | Background The effect of duty hour (DH) restrictions on postgraduate residents' acquisition of clinical competencies is unclear. We evaluated the relationship between DHs and competency-related knowledge acquisition using the General Medicine In-training Examination (GM-ITE). Methods We conducted a multicenter, cross-sectional study of community hospital residents among 2019 GM-ITE examinees. Self-reported average DHs per week were classified into five DH categories and the competency domains were classified into four areas: symptomatology and clinical reasoning (CR), physical examination and clinical procedure (PP), medical interview and professionalism (MP), and disease knowledge (DK). The association between these scores and DHs was examined using random-intercept linear models with and without adjustment for confounding factors. Results We included 4753 participants in the analyses. Of these, 31% were women, and 49.1% were in the postgraduate year (PGY) 2. Mean CR and MP scores were lower among residents in Category 1 (<50 h) than in residents in Category 3 (>=60 and <70 h; reference group). Mean DK scores were lower among residents in Categories 1 and 2 (>=50 and <60 h) than in the reference group. PGY-2 residents in Categories 1 and 2 had lower CR scores than those in Category 3; however, PGY-1 residents in Category 5 showed higher scores. Conclusions The relationship between DHs and each competency area is not strictly linear. The acquisition of knowledge of physical examination and clinical procedures skills in particular may not be related to DHs. In this study, we examined the relationship between duty hour (DH) and scores in each competency area of the General Medicine In-training Examination among residents affiliated with community hospitals in Japan. We found that acquiring knowledge of clinical reasoning medical interview skills professionalism and disease-related topics requires a certain level of DHs whereas that related to physical examination and clinical procedures may not be related to DHs. clinical competency community hospital duty hour restriction General Medicine In-training Examination Japan postgraduate resident source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Nagasaki K , Nishizaki Y , Hachisuka C , Shinozaki T , Shimizu T , Yamamoto Y , et al. Impact of duty hours on competency-related knowledge acquisition among community hospital residents. J Gen Fam Med. 2023;24 :87-93. 10.1002/jgf2.594 pmc1 INTRODUCTION Since 2018, workstyle reforms in Japan have affected all workers, including physicians and postgraduate residents. 1 Among them, reducing long working hours is considered to be one of the most important measures to improve the working environment. The Ministry of Health, Labor, and Welfare (MHLW) decreed that the upper limit of duty hours (DH) for physicians should be 960 h per year (equivalent to a 60-h work week), starting in 2024, while the limit for residents was set at 1860 h per year (equivalent to an 80-h work week), from an educational perspective. However, this decision remains questionable because of concerns about residents' health, as well as the lack of sufficient evidence on the relationship between DHs and educational outcomes. There has been minimal research on the association between the number of DHs and resident competencies in Japan as well as globally. One report analyzed the association between resident DHs and in-training examination scores in Japan. 2 The study demonstrated that fewer than 60-65 DHs per week were independently associated with lower performance; however, exceeding 65 DHs per week did not improve performance. 2 Another research further reported that Japanese residents with fewer than 60 DHs per week tended to spend less time in self-study than did those with more than 65 DHs per week. 3 Surveys about the impact of DH restrictions on residents in the United States found that, while resident health and burnout improved, there were negative effects on resident education and patient care. 4 , 5 , 6 These studies assessed the overall impact on resident education and suggested that DH restrictions had negative impacts on education. A systematic review researching the effect of DH restrictions on postgraduate medical education found that the effect on education was assessed mostly by measuring access to educational opportunities, total in-training examination scores, and caseloads. 7 In this context, we found no previous studies that directly examined the impact on DHs and residents' competency in various areas. Investigating the relationship between DHs and each resident's competency could prompt program directors, training program developers, and policymakers to consider ways to mitigate the negative educational effects of DH restrictions. In this study, we examined the relationship between DHs and scores in each competency area of the General Medicine In-training Examination (GM-ITE), an in-training examination in Japan among residents affiliated with community hospitals in Japan. 2 METHODS 2.1 Study populations In Japan, there is a 2-year postgraduate clinical training system. We conducted a multicenter, cross-sectional study of Japanese residents in postgraduate year 1 (PGY-1) and postgraduate year 2 (PGY-2) of their training. Before conducting the survey, we obtained written informed consent for study participation from all participants. The research consent document stated that the questionnaire results would be anonymized. An appropriate research ethics committee approved the study. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. In Japan, teaching hospitals are divided into three categories: independent hospitals, administrative hospitals, and cooperative hospitals. 8 , 9 Independent hospitals provide training programs almost exclusively on their own, while administrative hospitals operate programs in collaboration with cooperative hospitals. Many university hospitals are administrative hospitals, and many of them have programs, so-called tasukigake programs, where training at one cooperative hospital lasts 1 year. Thus, the work styles of university hospital residents are more diverse than those of community hospital residents. Because this study used the average DHs of the entire training program for analysis, university hospital residents, whose DHs would be difficult to interpret, were excluded from the study, and only community hospital residents were included in our study. As part of a training environment questionnaire completed immediately after the examination, participants were asked about average DHs during their residency program. The questionnaire also included the number of emergency department (ED) duties per month, the mean number of assigned inpatients, and self-study time per day. 2.2 Measurements The primary independent variable in this study was the average self-reported DHs per week. We defined DHs as the total hours of weekday work duty, night ED duty (including restrained time when not providing medical care), and weekend work duty. DHs were answered in eight categories, which were reorganized into five categories with 10-h increments: Category 1 (<50 h), Category 2 (>=50 and <60 h), Category 3 (>=60 and <70 h), Category 4 (>=70 and <80 h), Category 5 (>=80 h). Category 5 exceeded the maximum DHs for residents set by the MHLW. 1 Knowledge acquisition of resident competencies was assessed using the scores of the GM-ITE. The GM-ITE is an in-training examination conducted in Japan. It is administered each year by the Japan Institute for Advancement of Medical Education Program (JAMEP, a nonprofit organization in Tokyo, Japan), and training programs voluntarily participate in the examination. The GM-ITE is designed to provide objective and reliable clinical knowledge assessment of postgraduate residents, with results shared with the residents and their residency programs. 10 , 11 The examination contains 60 multiple-choice questions, which are grouped into four major competency areas: symptomatology and clinical reasoning (CR, 18 questions), physical examination and clinical procedure (PP, 18 questions), medical interview and professionalism (MP, 6 questions), and disease knowledge (DK, 18 questions). Although both CR and DK areas contain case-based questions on diagnosis and management, CR mainly focuses on the diagnosis, and DK focuses on management. In the PP area, we applied audio and video questions. We excluded one question in the PP area after the examination as an inappropriate question. Participants completed the GM-ITE from January 21 to 28, 2020. 2.3 Statistical analyses We examined the association between resident DHs and each competency area score (one point per question) using random-intercept linear models, accounting for hospital variability as normal random intercepts. Category 3 was set as the DH reference for the analyses, considering that 60 h per week was the basic upper limit of DHs for all doctors. 1 We excluded residents who did not provide information about DHs from the analyses. We repeated the analyses, stratified by PGY. We adjusted for the following variables that could potentially be associated with the total GM-ITE score: sex, PGY, ED duties, number of assigned inpatients, and self-study time. 2 , 12 All analyses were performed using SAS version 9.4 (SAS Inst.). 3 RESULTS The GM-ITE survey included 6869 postgraduate residents from 539 residency programs. The survey response rate was 89.7% (6164/6869). We excluded 571 residents who did not provide DH information, and also excluded another 840 university and university-affiliated hospital residents. Finally, the analysis included 4753 participants. Among them, 31% were women and 50.9% were PGY-1. The mean (+- standard deviation) of total GM-ITE scores of all the participants was 29.7 +- 5.3. The scores in the various competency areas were as follows: CR, 9.9 +- 2.3; PP, 9.2 +- 2.3; MP, 2.9 +- 1.2; and DK, 8.2 +- 2.2. Table 1 summarizes resident characteristics categorized by DHs, and Table S1 in Appendix S1 lists them stratified by PGY. TABLE 1 Characteristics. Baseline characteristics of residents categorized by DHs Variable C1: <50 h C2: >=50 and <60 h C3: >=60 and <70 h C4: >=70 and <80 h C5: >=80 h N = 502 N = 1393 N = 1542 N = 580 N = 736 Male sex (%) 65.1 69.6 69.5 66.7 70.9 PGY-2 (%) 52.2 47.2 48.6 49.8 51.4 ED duties per month (%) None 6.2 1.5 1 1.7 0.8 1-2 24.8 13.7 7.6 7.2 4.6 3-5 62.7 78.3 79.2 74.3 66.3 6 or more 6 6.1 11.6 16.6 27.6 Unknown 0.4 0.4 0.6 0.2 0.7 Assigned inpatients (%) 0-4 30.3 21.4 16 13.3 9.9 5-9 60.4 65.4 64.4 60.7 55 10-14 6.6 9 13.7 17.8 18.4 15 or more 1.4 1.2 2.5 5.2 14 Unknown 1.4 3.1 3.3 3.1 2.7 Self-study time per day (%) None 3.4 3.4 3.4 4 6.2 0-30 min 49.5 37.1 34.3 30.3 32.9 31-60 min 36.5 43.6 44.3 43.8 38.5 61-90 min 9.2 13.1 14.9 17.8 17.5 91 min or more 1.4 2.7 3.1 4.1 4.9 Note: Calculation of the average duty hours was based on the sum of weekday work duty, night emergency department (ED) duties, and weekend work duty. Abbreviations: C1-C5, Category 1 to Category 5; DHs, duty hours; ED, emergency department; PGY, postgraduate year. Figure 1 and Table S2 in Appendix S2 present the results of the analyses assessing the association between resident DHs and each competency area score. Compared with residents in Category 3, mean CR scores were lower among residents in Category 1 (mean score difference [MSD], -0.46; 95% CI, -0.70 to -0.23; p < 0.001) and Category 2 (-0.19; -0.36 to -0.03; p = 0.02). Similarly, mean DK scores were lower among residents in Category 1 (-0.33; -0.55 to -0.11; p = 0.004) and Category 2 (-0.22; -0.37 to -0.06; p = 0.01) than in residents in Category 3. Compared with the Category 3 group, Category 1 residents scored lower on PP (-0.26; -0.49 to -0.03; p = 0.03) and MP (-0.15; -0.28 to -0.03; p = 0.01). FIGURE 1 Estimates of mean score differences for each subcategory score between residents' duty hour categories, with multivariable adjustments. Note: Non-responders for Emergency Department duties and inpatients were included in "unknown." Non-responders for self-study time were excluded from the multivariable analysis. Error bars indicate 95% confidence interval. C1-C5, Category 1 to Category 5. After adjusting for possible confounding variables, mean DK scores were lower among residents in Category 1 (-0.24; -0.47 to -0.02; p = 0.03) and Category 2 (-0.19; -0.35 to -0.03; p = 0.02) than among residents in Category 3. Compared with the Category 3 group, Category 1 residents scored lower on CR (-0.38; -0.62 to -0.15; p = 0.02) and MP (-0.15; -0.27 to -0.02; p = 0.02). After adjustment, there was little or no mean score difference among the DH Categories in the PP competency areas. Figure 2 and Table S3 in Appendix S2 present the adjusted results of the association between resident DHs and each competency area score stratified by PGY. PGY-2 residents in Categories 1 and 2 had lower CR scores than those in Category 3; however, PGY-1 residents in Category 5 had higher CR scores than those in Category 3. DK scores were lower for PGY-1 Category 1 residents than for the reference category residents, but there was no difference in DK scores between categories for PGY-2 residents. MP scores were lower for PGY-2, but not for PGY-1, Category 1 residents than for the reference category residents. There was no difference in mean scores between each DH Category for PGY-2 and PGY-1 residents in the PP competency areas. FIGURE 2 Estimates of mean score differences for each subcategory score between categories of residents' duty hours, with multivariable adjustments stratified by postgraduate year. Note: Non-responders for Emergency Department duties and inpatients were included in "unknown." Non-responders for self-study time were excluded from the multivariable analysis. Error bars indicate 95% confidence interval. C1-C5, Category 1 to Category 5. 4 DISCUSSION In this study of the effect of DHs on residents' competencies in different areas, we found that, overall, community hospital residents with <60 DHs per week had lower DK scores on the GM-ITE than those with 60-70 DHs per week, whereas those with >70 DHs per week did not have higher scores. Furthermore, <50 DHs were associated with lower CR and MP scores. When we stratified the analysis by PGY, CR scores decreased for residents in the <=60 DHs group for PGY-2 and increased for those in the >=80 DHs for PGY-1. In residents with <50 DHs, the DK scores decreased only for PGY-1 residents, and the MP scores decreased only for PGY-2 residents. Thus, there were discrepancies in the association between DHs and knowledge acquisition and its application in each competency area. Knowledge acquisition for the competency areas of DK and CR was found to be related to resident DHs, with a positive trend up to 60-70 DHs per week, but no increase in the score when DHs exceeded 70 h. For CR knowledge acquisition, working more during PGY-1 temporarily raised the score, but for those in PGY-2, the scores of residents who worked more than 60 h per week eventually seemed to reach a plateau. Nevertheless, reducing DHs of PGY-1 could be a barrier to CR skill acquisition. Although these adjusted score differences are about 2%-4% in each category, the "cumulative" difference in scores by DHs was not negligible, as the resident DH policies affect the working conditions of almost all residents. These two competency areas can be assessed by written examinations, and are generally the primary assessment items on the in-training examination. There was no clear upward or downward trend in the impact of work-hour restrictions on the resident performance in in-training examinations in the United States in the fields of internal medicine, emergency medicine, and surgery. 13 , 14 , 15 , 16 The current variation in DHs in Japan may reflect the number of assigned inpatient cases. The number of patient encounters correlated with performance in in-training examinations in internal medicine residents, family medicine residents, and students on internal medicine clerkships. 17 , 18 , 19 Future research should examine the relationship between resident DHs and the number of clinical encounters, and the relationship between these and residents' clinical knowledge in Japan. The relationship between knowledge acquisition and work hours in the MP and PP competency areas showed a different relationship than that in the CR and DK areas. MP scores appeared to be low for residents who worked less than 50 h per week, particularly in the PGY-2. A 50-h work week means almost no overtime work, which implies that weekend work and nighttime ED duties are almost nonexistent. This is quite different from the work style of a typical hospital doctor, and such a learning environment is unlikely to foster professionalism. On the contrary, DHs appeared to have no effect on the PP scores. Clinical training in Japan may not provide sufficient education on these competency areas. In particular, previous studies have pointed out a lack of education on professionalism. 20 Another possible explanation is that DH variation may have both positive and negative effects on these competencies, and the effects may be offset. 21 For scores in the PP area, there was no clear relationship between DHs and the acquisition of knowledge. There are two possible explanations for this observation. First, Japanese clinical residents may have acquired sufficient knowledge of these competency areas during medical school training. Medical students in Japan must pass an Objective Structured Clinical Examination, which evaluates skills in physical examination, medical interviewing, and clinical procedures. Second, postgraduate training may not adequately teach these competencies, particularly physical examination skills. 22 Even if there is a large volume of case experience, teaching and feedback may not be sufficient, possibly resulting in a lack of improved performance of residents. In this study, we found that working more than 60-70 h per week did not increase scores in any competency area for PGY-2 residents nearing the end of their training, although the relationship between scores in each of the competency areas and DHs was different. McCoy et al. proposed four models for the relationship between patient encounter volume and knowledge acquisition: a linear relationship, threshold, Yerkes-Dodson curve (positive relationship up to a certain point, negative relationship thereafter), and null. 19 In their study, the patient encounter volume and in-training examination scores were positively associated, but in our study, we found that the relationship of DHs with CR and DK scores had a threshold. The in-training examination score of residents may improve as the patient encounter volume increases but increasing DHs further will not improve scores. Therefore, it may be necessary to set an appropriate upper limit for DHs. Our recent study also found that self-study time was shorter in residents who worked less than 60-65 h per week. 3 Taken together with the findings of this study, 60-70 h per week is a benchmark for an appropriate upper limit on DHs. However, residents' health and patients' safety are also important factors in determining DHs. Thus, further research will be needed in the future. There were several limitations in this study. First, the number of questions for each competency area is small and may not provide a reliable assessment. In general, in-training examinations are reportedly adequate, with a reliability coefficient of 0.80 at around 100 questions; however, the GM-ITE may not be as accurate, because it contains 60 questions in total and fewer questions for each competency area. 23 Additionally, there are some concerns about the validity of the GM-ITE itself. A previous study showed that GM-ITE scores correlated well with those of a foreign examination, but their relationship to actual clinical performance has not been investigated. 11 Second, the GM-ITE is a written test and, by its nature, can only assess knowledge and related cognitive abilities. Therefore, GM-ITE scores are not necessarily a guarantee of actual clinical competence. In this study, the areas of physical examination, clinical skills, communication, and professionalism were assessed by evaluating the acquisition of knowledge about them and their application. However, we do not know whether this reflects performance in real clinical practice. Third, DHs were self-reported in the survey and may not have been reported accurately. The trend of bias in self-reported DHs may be different for each group. In addition, residents who did not report their working hours (571 excluded individuals) performed worse on the examination than those who reported them (mean 29.7 [SD 5.3] vs. 28.9 [SD 5.6]). The residents who performed worse in the examination were more likely to refuse to participate in the study. Fourth, on average, only one-third of all residents take the GM-ITE, which may introduce selection bias. Participation in GM-ITE is voluntary in training hospitals, which may be more education-oriented, and residents in-training hospitals may be more motivated to improve their skills. In addition, we excluded university hospital residents from our analysis as they tend to have greatly variable working patterns. To allow for a comparison of residents at university and community hospitals, the baseline characteristics of the university hospital residents are shown in Table S4 in Appendix S3. A summary of the examination scores is presented in Table S5 in Appendix S4. University hospital residents appear to have less ED duty, fewer assigned inpatients, less time for self-study, and lower scores than community hospital residents. Fifth, the study did not assess residents' baseline clinical knowledge. Therefore, to measure the impact of working hours on resident improvement directly, adjusting for baseline GM-ITE scores, national examination scores, and performance during medical school is necessary. Sixth, some community hospitals also have "tasukigake" programs. Thus, there are residents in community hospitals who work in a variety of work locations similar to those in university hospitals. However, this study did not examine the number of community hospital residents who partook in "tasukigake" programs. In conclusion, our results suggest that the knowledge acquisition of CR, medical interviews, professionalism, and disease-related topics requires a certain level of DHs, while the application of knowledge of physical examination and procedures may not be related to DHs. In addition, the limit of 80 DHs per week starting in 2024 will have only a limited impact on the residents' acquisition of competency-related knowledge. In the future, these competencies should be evaluated using more suitable assessment methods, and their relationships with DHs should be investigated in more detail. CONFLICT OF INTEREST The JAMEP was involved in collecting and managing data as the GM-ITE administrative organization. It did not participate in designing and conducting the study; data analysis and interpretation; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. Dr. Nishizaki received an honorarium from the JAMEP as the GM-ITE project manager. Dr. Tokuda is one the JAMEP directors. Dr. Kobayashi received an honorarium from the JAMEP as a speaker for the JAMEP lecture. Dr. Shimizu and Dr. Yamamoto received an honorarium from the JAMEP as exam preparers of the GM-ITE. Dr. Nishizaki, Dr. Tokuda, Dr. Kobayashi, Dr. Shimizu, and Dr. Yamamoto were not involved in the analysis. ETHICS APPROVAL STATEMENT The Ethics Review Board of Juntendo University School of Medicine approved the study. PATIENT CONSENT STATEMENT We obtained informed consent to participate in this study from all participants before the survey. The research consent document stated that the questionnaire results would be anonymized. Supporting information Appendix S1-S4 Click here for additional data file. ACKNOWLEDGMENTS This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors thank members of JAMEP and the question development committee and the peer-review committee of the GM-ITE for their assistance. The authors thank Enago (www.enago.jp) for the English language review. DATA AVAILABILITY STATEMENT Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data are not available. |
PMC10000280 | Objective Chronic obstructive airway disease (COPD) is characterized by airflow limitation due to airway and/or alveolar abnormalities with significant extra-pulmonary manifestations. Bone health impairment is an extra-pulmonary complication of COPD which is less well studied in India. Moreover, it can contribute to significant morbidity and mortality. Hence, we aim to estimate the prevalence of osteoporosis and metabolic parameters of adverse bone health in patients with COPD. Methods In this case control study, male subjects aged 40-70 years with COPD attending the respiratory outpatient clinic in a tertiary care hospital were recruited over a period of 2 years and the control population were derived from the historical cohort who were apparently healthy with no obvious diseases. Metabolic parameters of bone health measured from fasting blood samples were calcium, albumin, alkaline phosphatase, phosphorous, parathormone, creatinine, 25-hydroxy vitamin D, and testosterone. Bone mineral density (BMD) was estimated using DXA scan and the World Health Organization (WHO) criteria was used to categorize into osteoporosis, osteopenia, and normal BMD based on the T-score at femoral neck, lumbar spine and distal forearm. Pulmonary function tests and 6 minute walk test were performed if they had not been done in the previous 3 months. The associations of COPD with osteoporosis were analyzed using linear regression analysis and effect size are presented as beta with 95% confidence interval. Results Of the 67 participants with COPD enrolled in the study, osteoporosis was present in 61% (41/67) and osteopenia in an additional 33% (22/67) of the cases, which was higher when compared to the control population (osteoporosis 20% [50/252] and osteopenia 58% [146/252]). In regression modeling, there was a trend toward adverse bone health with advanced age, low body mass index, low forced expiratory volume in 1 second and testosterone deficiency in COPD. Conclusion Individuals with COPD have a substantially higher prevalence of osteoporosis and osteopenia, up to almost twice that of the general population, with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. Hence, bone health assessment should be a part of comprehensive COPD care to prevent adverse consequences due to poor bone health. Chronic obstructive airway disease (COPD) is a multimorbid disorder with two thirds affected have at least one extra-pulmonary complication. Bone health in COPD is least studied in developing nations and, in our study, we have reported that osteoporosis is twice more common in COPD than in healthy individuals and with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. COPD osteopenia osteoporosis vitamin D deficiency FLUID grant source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Jeeyavudeen MS , Hansdek SG , Thomas N , Balamugesh T , Gowri M , Paul TV . Bone health in ambulatory male patients with chronic obstructive airway disease - A case control study from India. Aging Med. 2023;6 :63-70. doi:10.1002/agm2.12239 pmc1 INTRODUCTION Global Initiative for Chronic Obstructive Lung Disease (GOLD), defines chronic obstructive pulmonary disease (COPD) as a progressive disease characterized by persistent airflow limitation. 1 COPD is a preventable and treatable disease; however, it contributes to significant morbidity in affected individuals due to its pulmonary and extra-pulmonary effects. The burden of COPD is steadily increasing both in developed and developing countries. The recent World Health Organization (WHO) report estimates that around 328 million people around the world are living with moderate to severe COPD and more than 3 million deaths in 2005 were attributed to COPD or its systemic complications. 2 This corresponds to 5% of deaths reported globally, although this number may be higher given that 90% of deaths occurred in developing countries where the reporting systems are suboptimal. COPD is the second leading cause of disease burden in India, contributing to 8.7% of the total deaths and 4.8% of the total disability adjusted life years (DALYs). 3 , 4 , 5 Death due to COPD is higher in male patients, and people with longer disease duration, frequent exacerbations, and significant extrapulmonary complications. 6 With advances in the treatment of COPD over the last 2 decades, people live longer, with more than two thirds affected by at least one extrapulmonary complication. 6 , 7 Cardiovascular comorbidity is one of the most feared extra pulmonary complications, characterized by increased incidence of systemic and pulmonary arterial hypertension, congestive cardiac failure, and arrhythmias. 8 In a study by De Luise et al, there was a significant increase in the 30-day mortality after a hip fracture in patients with COPD when compared with patients without COPD. 9 This additional risk extends well beyond the immediate postoperative period with the mortality rate reaching nearly three folds even after a year. Hence, non-communicable diseases, like osteoporosis, has emerged to significantly contribute to the disease morbidity and mortality. The increased risk of osteoporosis in patients with COPD has been attributed to the systemic nature of the disease and its treatment, which requires glucocorticoids, especially with those with frequent exacerbation. 10 Major societal guidelines do not recommend COPD as risk factor for osteoporosis screening. 11 , 12 Fracture Risk Assessment (FRAX), one of the most popular assessment tools, does not include COPD as a risk factor in its assessment algorithm but has current smoking and glucocorticoid use as factors contributing to higher risk score. 13 QFracture, another commonly used risk assessment tool, includes COPD as a risk factor for major osteoporotic fracture. 14 Both these risk scores do not take into account factors like dose and repeated exposure to oral steroid and high dose inhaled glucocorticoids, which are commonly used for exacerbation in patients with uncontrolled COPD, and can independently predispose them to increased risk of fracture and added morbidity. There is also paucity of data on bone health in patients with COPD in developing countries like India. Hence, we have designed this study to estimate the prevalence of osteoporosis and other metabolic bone health indices in this cohort of patients. 2 SUBJECTS AND METHODS This was a case control study conducted between September 1, 2012, and June 30, 2014. The study was approved by the institutional review board. The cases were consecutive male patients with COPD between 50 and 70 years of age attending the Respiratory Medicine outpatient services were screened, and those with known COPD, or newly diagnosed to have COPD as per the GOLD criteria, were enrolled into the study. 1 Subjects of this age and gender were selected to homogenize the study population and to minimize the influence of hormonal changes affecting bone health seen in the extreme of ages, particularly in women. Subjects with hyperthyroidism, hyperparathyroidism, Cushing's syndrome or any other severe systemic illness, immobilization, and those who were already on calcium and vitamin D were excluded from the study. The control population was derived from the cluster random sampling of 242 individuals from the community who were apparently healthy without COPD and were of similar age and gender to the cases. 15 They were also from the same region, and this was done to avoid the confounding effect of ethnicity influencing bone health. The prevalence of osteoporosis in the control population at any site was 20% (15% at the lumbar spine and 10% at the femoral neck), and further details of this study can be found elsewhere. 15 Written informed consent was obtained from all subjects. Data were obtained regarding age, symptoms, exacerbation triggers of COPD, and the severity of the disease. A detailed medication history, including oral and inhaled glucocorticoid frequency, dose, and duration were documented along with the presence of pre-existing comorbidities (eg, diabetes, hypertension, and dyslipidemia). The doses of inhaled glucocorticoids were calculated for the budesonide equivalent dose. Patients were then categorized into high dose and less than high dose based on the cumulative daily inhaled glucocorticoids dose. The high dose category patient received a cumulative dose of budesonide > 800 mg/day and the latter received less than 800 mg/day. The cumulative dose of oral glucocorticoids was calculated for the prednisolone equivalent dose. A validated semiquantitative food frequency questionnaire (FFQ) was used to calculate the dietary calcium intake by 24-hour dietary recall method. 16 Sunlight exposure was calculated from the duration for which the patient's body surface area was directly exposed to the sunlight such that when the shadow formed is smaller than the real image. 17 All subjects underwent spirometry using the Jaeger spirometer and a 6-minute walk test to make assessments as per the American Thoracic Society Guidelines. 18 The GOLD criteria were used to categorize patients into the various disease stages. 1 The body mass index, airflow obstruction, dyspnea, and exercise (BODE) index, which is a composite marker of disease severity that takes into consideration of the systemic nature of the disease, was calculated for all patients. 19 The mortality risk according to the BODE index is as follows: a score greater than 7 is associated with a 30% 2-year mortality, a score of 5-7 is associated with a 15% 2-year mortality and < 5 is associated with 10% 2-year mortality, respectively. 20 Assessment of bone mineral density (BMD) was performed using the Hologic DXA Discovery QDR 4500 at lumbar spine, femoral neck, and distal forearm by the same technician. The reference standard consisted of healthy young White subjects used by the manufacturer's database with precision of 2% and the WHO criteria for osteoporosis based on T-score were used to categorize the patients. 21 Early morning fasting blood samples were collected in order to assess the following metabolic bone and other biochemical parameters: serum calcium (normal [N]: 8.3-10.4 mg/dL), phosphorus (N: 2.5-4.6 mg/dL), albumin (N: 3.5-5.0 g/dL), alkaline phosphatase (ALP; N: 40-125 U/L), creatinine (N: 0.5-1.4 mg/dL), 25-hydroxyvitamin D3 (25[OH]D; N: 30-70 ng/mL), intact parathyroid hormone (iPTH; N: 8-50 pg/mL) and C-reactive protein (CRP; N: < 6 mg/L), total testosterone (N: 300-1030 ng/dL), and cortisol (N: 7-25 mg/dL). The biochemical variables, such as calcium, phosphorus, creatinine, albumin, and ALP were measured in a fully automated computerized microanalyzer (Hitachi model 911; Boehringer Mannheim). The intra-assay and inter-assay coefficients of variation of the variables being studied from these machines were 1%-5%. Intact PTH, testosterone, and 25(OH)vitamin D were measured by a chemiluminescence immunoassay using an Immulite analyzer 2000. Vitamin D level was defined as sufficient for 25 (OH) D levels more than 30 ng/mL and deficient for levels < 20 ng/mL. CRP was estimated by immunonephelometry (BN ProSpec; Dade Behring) according to the manufacturer protocol using the CardioPhase highly sensitive CRP reagents. Hypogonadism was defined as 8 am total serum testosterone < 300 ng/dL. 3 SAMPLE SIZE CALCULATION AND STATISTICAL ANALYSIS The sample size was calculated using prevalence data from a previously published study from India. 14 A sample size of 64 subjects was required to study the prevalence of low bone density (osteoporosis and osteopenia) assuming a prevalence of 80% based on the previous Indian study using the equation 4 pq/d2 with a precision of 10%. The continuous variables were described using means and standard deviations or median and interquartile range (IQR) depending on normality. All categorical variables were summarized by using frequencies and percentages. Association for continuous variables with low bone density was done using Independent t test and for categorical associations chi-square test was used. The T-scores of each region were considered as continuous outcome as the larger percent of the cohort has either osteopenia or osteoporosis. Linear regression model was used to determine significant predictors. Univariate model was used to define the individual effect of each predictor. Multivariate model was constructed adjusting for variables with entry criteria of P value < 0.20. The effect sizes were presented with beta (and 95% confidence interval [CI]). For all analyses, the significance level was determined for P < 0.05. The results of this study were compared with a historical cohort of previously published subjects from the same ethnicity without COPD. 15 All statistical analyses were done using STATA/IC version 16.0. 4 RESULTS This study included 67 male subjects diagnosed with COPD based on the GOLD criteria. The mean (+-SD) age group of the study population was 60 (+-6) years, and the mean duration of COPD was 48 months (Table 1). TABLE 1 Baseline characteristics of the study subjects Overall (n = 67) Normal (n = 6) Osteopenia (n = 33) Osteoporosis (n = 28) P valued Age (y) a 60.2 +- 6.9 59.5 +- 6.8 59.2 +- 7.3 61.6 +- 6.4 0.176 Current smokers c 7 (10) 0 (0) 2 (6.1) 5 (17.9) 0.093 No. of pack years b 30 (20, 46.5) 30 (28, 40) 24 (15, 44.5) 36 (25, 50) 0.176 Duration of COPD in months b 48 (24, 72) 18 (12, 39) 60 (36, 84) 54 (24, 72) 0.673 6 MWD (meters) a 348 +- 92.1 318.9 +- 84.3 370.2 +- 97.1 328 (84) 0.134 FEV1 a 42.2 +- 18.6 51.9 +- 21.8 44.3 +- 19.6 37.5 +- 16 0.085 FVC a 61.3 +- 17.2 71.8 +- 14.9 61 +- 18.8 59.5 +- 15.4 0.464 FEV1/FVC a 67.6 +- 17.5 70.3 +- 20.9 72.2 +- 18.8 61.7 +- 13.4 0.017 Oral steroid dose b 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 20) 0.287 Oral steroid duration in the last 1 y b 0 (0, 0) 0 (0, 0) 0 (0, 0) 0 (0, 5) 0.282 Dietary calcium intake b 1156.3 +- 264.2 1048.3 +- 231.4 1157.9 +- 291.6 1177.5 +- 238.5 0.581 Abbreviations: 6 MWD, 6 minute walking distance; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; IQR, interquartile range. a Summarized using mean +- SD. b Summarized using median (IQR). c Presented as n (%). d The P values are presented comparing osteoporosis as one group and osteopenia and normal clubbed together. The majority of the patients were distributed equally in stages II, III, and IV, there was only one patient with stage I disease. The frequency of patients in three BODE categories- < 5, 5-7 and more than 7 were 8, 7 and 52 patients, respectively. Nine of the study participants received high dose inhaled glucocorticoids of which one had osteoporosis and the rest had osteopenia. Seven patients received oral glucocorticoids in the last 2 years. As expected, these patients were in stages III and IV disease category and had a high BODE index score. The prevalence of vitamin D deficiency was 52% (N: 35/67). Biochemical hypogonadism was seen in 31% (N: 21/67). Duration of sunlight exposure was equal in all the groups. The prevalence of osteoporosis at any one site in this study was found to be 61% (41/67). The prevalence of osteoporosis at the lumbar spine and femoral neck were almost equal with 24% (16/67) at the lumbar spine and 25% (17/67) at the femoral neck. The prevalence of osteopenia at the lumbar spine and femoral neck was found to be 47% (31/67) and 53% (36/67), respectively. There was an increased prevalence of osteoporosis of 33% (22/67) and osteopenia 33% (22/67) at the distal forearm compared to the other sites . FIGURE 1 Prevalence of osteoporosis between cases and controls across different sites. In the univariate regression model, at least one site of lower T-score for osteoporosis in male patients with COPD were significantly associated with age, body mass index (BMI), smoking status, forced expiratory volume in 1 second (FEV1) and FEV1/FVC (Table 2). BMI remained significantly associated with lower T-score even in the multivariate analysis (Table 3). TABLE 2 Univariate associations of T-scores at each site with clinical and demographical variables Variables Lumbar spine Femoral neck Distal forearm Age, y 0.033 (-0.016, 0.081) -0.022 (-0.056, 0.011) -0.066 (-0.121, -0.011)* BMI 0.096 (0.034, 0.158)** 0.084 (0.042, 0.125)** 0.124 (0.053, 0.196)** Current smoker -0.022 (-1.112, 1.068) -0.516 (-1.268, 0.236) -1.294 (-2.533, -0.055)* FEV1 0.021 (0.003, 0.038)* 0.012 (0.000, 0.025) 0.007 (-0.014, 0.028) FEV1/FVC 0.024 (0.005, 0.042)* 0.012 (-0.001, 0.026) 0.014 (-0.008, 0.037) GOLD stage -0.318 (-0.735, 0.100) -0.121 (-0.420, 0.179) 0.059 (-0.447, 0.566) BODE index (> 7) -0.220 (-0.884, 0.444) -0.128 (-0.593, 0.337) 0.240 (-0.540, 1.021) 25(OH) vitamin D 0.079 (-0.322, 0.480) -0.020 (-0.301, 0.261) -0.227 (-0.695, 0.241) Serum iPTH -0.107 (-0.783, 0.568) 0.015 (-0.458, 0.487) 0.223 (-0.568, 1.015) Testosterone level (>= 300 ng/dL) 0.244 (-0.472, 0.960) 0.292 (-0.206, 0.789) -0.067 (-0.911, 0.777) Abbreviations: BMI, body mass index; BODE, body-mass index, airflow obstruction, dyspnea, and exercise; CI, confidence interval; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; iPTH, intact parathyroid hormone. Note: Each cell represents a single regression equation coefficient (95% CI); ***P < 0.001; **P < 0.01; *P < 0.05. TABLE 3 Multivariate associations of segmental t-scores with clinical and demographic variables Variables Lumbar spine Femoral neck Distal forearm Age, y 0.041 (-0.007, 0.090) -0.016 (-0.049, 0.016) -0.056 (-0.111, -0.001) BMI 0.105 (0.031, 0.179)** 0.064 (0.014, 0.113)* 0.064 (-0.020, 0.148) Current smokers 0.351 (-0.738, 1.440) -0.292 (-1.028, 0.445) -1.002 (-2.244, 0.240) FEV1 0.014 (-0.017, 0.044) 0.017 (-0.003, 0.038) 0.026 (-0.008, 0.061) BODE index (> 7) 0.105 (-1.062, 1.271) 0.435 (-0.354, 1.223) 0.975 (-0.356, 2.306) Testosterone level (>= 300 ng/dL) 0.358 (-0.330, 1.046) 0.413 (-0.052, 0.878) 0.198 (-0.587, 0.982) Abbreviations: BMI, body mass index; BODE, body-mass index, airflow obstruction, dyspnea, and exercise; CI, confidence interval; FEV1, forced expiratoryvolume in the first second. Note: Each row represents a single regression equation coefficient (95% CI); ***P < 0.001; **P < 0.01; *P < 0.05. The mean BMD in the present study was compared with age and gender-matched controls without COPD or other chronic disease affecting bone health (Table 4). 15 The mean BMD at the femoral neck for patients with COPD (0.692 kg/m2) was significantly lower when compared with healthy subjects of similar age group, ethnicity, and gender (0.761 kg/m2, P < 0.001). A similar finding was also found in the lumbar spine region (mean BMD patient with COPD: 0.906 kg/m2 vs. normal subject 0.943 kg/m2, P = 0.024). TABLE 4 Biochemical parameters and BMD of the study subjects compared with the historical cohort Parameters COPD (n = 67) Mean (SD) Non-COPD 15 (n = 252) Mean (SD) Unpaired t test P value Serum calcium (mg/dL) 9.32 (0.56) 8.82 (0.43) < 0.001 Serum PO4 (mg/dL) 3.65 (0.75) 3.9 (0.5) 0.001 Serum iPTH (pg/mL) 57.11 (28.59) 44.5 (25.6) < 0.001 Serum alkaline PO4 (U/L) 83.84 (28.42) 73.5 (21.4) 0.001 Serum 25 OH vitamin D (ng/mL) 25.25 (16.50) 20.4 (8.3) < 0.001 Serum testosterone (ng/dL) 381.15 (173.71) 620 (124) < 0.001 ESR (mm/h) 17.37 (12.93) - CRP (mg/L) 11.04 (13.89) - Bone mineral density Femoral neck (g/cm2) 0.692 (0.130) 0.761 (0.124) < 0.001 Lumbar spine (g/cm2) 0.906 (0.145) 0.943 (0.111) 0.024 Distal forearm (g/cm2) 0.588 (0.089) - Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; ESR, erythrocyte segmentation rate; iPTH, intact parathyroid hormone. 5 DISCUSSION In the current study, the prevalence of osteoporosis in men with COPD was 61%, and hypovitaminosis D was seen in 52% of the study subjects. These results along with the previously published data confirms that people with COPD have weaker bone mass, and prevalence of osteoporosis is nearly doubled when compared with healthy men in the same community (Table 4). 15 , 22 , 23 , 24 The osteoporosis prevalence from our study matches data from two other previously published reports from India. The first was published by Bhattacharya et al who measured BMD using calcaneal ultrasound. 22 In the second study by Hattiholi et al, the prevalence of osteoporosis and osteopenia were 66.7% and 19.6%, respectively. 23 However, other parameters relating to adverse bone health were not reported in both these studies. The prevalence of osteoporosis reported in these Indian studies were more when compared with Western studies. 25 , 26 In the multicentric TOwards A Revolution of COPD Health Study (TORCH trial), the prevalence of osteoporosis and osteopenia were 18% and 41%, respectively. 27 The reason for an increased prevalence of osteoporosis in our study and other studies reported from India may be due to an increased community prevalence of osteoporosis and vitamin D deficiency, an advanced stage of the disease, and a higher dose of glucocorticoids used for treatment. 28 The increased risk for osteoporosis in patients with COPD is due to the systemic nature of the disease, glucocorticoid intake, change in body composition and weight, decreased activity, reduced exercise reserve, and reduced sunlight exposure due to dyspnea associated with mobility during advanced stages of the disease. What causes this systemic dysfunction is not clearly understood, but there are some hypotheses that are postulated and tested. The two important ones are a systemic spillover theory and a compartment model. In the systemic spillover hypothesis, it is assumed that there is a spillover of the cytokines and inflammatory mediators due to chronic inflammation in the lungs into the systemic circulation. 29 , 30 The compartment model states that there are two or more compartments where the disease process is ongoing simultaneously. 31 , 32 The distant organ or systems affected, as mentioned earlier, were the cardiovascular system, adipose tissue, and bone, and the primary organs are the lungs. The mean BMI of our study population was 23 kg/m2 (2 SD +- 5.06). BMI in our study population is similar to that seen in the other two studies reported from India as compared to the Western study population who have a much higher BMI. 22 , 23 In our study, BMI was positively correlated with the BMD. Mechanical bone loading increases the bone strength and remodeling but it also ultimately depends on the fat free mass that contributes to this increased effect. 33 Fat free mass in patients with COPD has been reported to be low and this depends on the severity of disease category with a decrease of 20% in a clinically stable patient with COPD to 41% in severe cases those requiring pulmonary rehabilitation when compared to the age and gender matched general population. 34 Leptin, an adipocyte derived hormone has a biphasic effect on bone modeling and re-modeling. At low concentration, it promotes proliferation and differentiation of osteoblasts but at high concentration it inhibits the bone formation both through central and peripheral effects. 35 Moreover, this effect of leptin is more pronounced in obese women with COPD, who have high circulating leptin levels. 36 Hence, body weight and BMI have a complicated relationship with bone health. The other parameters that were significant in the regression modeling were testosterone deficiency and FEV1 level. It is well-established that testosterone has positive effects on bone formation by its direct action and indirect action through aromatization to estrogen. 37 Testosterone exerts its direct effects by binding to androgen receptors expressed on the pre-osteoblast and helps its maturation whereas estrogen influences bone formation and inhibits resorption through its action on the estrogen receptor. 21 FEV1 had a positive effect on the bone health and is likely related to the systemic state of the patient, as a higher FEV1 indicates better lung function. Hence, this will make the individual mobilize better for proper bone loading, sunlight exposure, and lower steroid requirements for disease control. The inflammatory markers, erythrocyte segmentation rate (ESR) and CRP were elevated in our study population. Suppression of bone formation and an increase in osteoclastogenesis in chronic inflammatory disease has been shown to induce proteins, such as Dickopf 1 and sclerostin. 38 By inhibition of the Wnt pathway, these proteins along with several other cytokines, such as IL-15, interferon gamma, IL-17 MCP-4 (monocyte chemoattractant protein), and TNF-a blunt the bone formation there by leading to osteoporosis and its sequelae. 39 , 40 Regular use of oral glucocorticoids significantly increases the risk of osteoporosis. 41 This is due to the uncoupling of bone formation as well as due to the direct toxic effect of steroids on the osteoblast. High dose inhaled glucocorticoids are known to have systemic effects with adverse bone effects and dose-related adrenal suppression. 42 Our study had only nine participants (14% percent) on high dose inhaled glucocorticoid and this did not achieve statistical significance with adverse bone health, potentially due to the reduced sample size. But this finding is similar to TORCH trial, which did not show an increase in bone loss in people taking inhaled glucocorticoids when compared with those on placebo. 27 Although the study population resides in and around Vellore (Vellore, 12 degrees55'N, longitude 79 degrees11'E) where there is abundant sunlight throughout the year, only 13% had adequate exposure to sunshine. Sunlight is an abundant source for vitamin D, which in turn is an intermediate factor contributing to the bone health. 43 Exposure to the sunlight should be at the time when the vitamin D synthesis is at its peak, and this usually happen at early noon when the ultraviolet B component of the sunlight is at its maximum. The surrogate marker for this in practical sense would be when the length of the shadow formed is less than the individual's height and the recommended duration of exposure is for at least 30 minutes. 28 Because of restriction to outdoor activity, due to dyspnea, and in the late stages due to the requirement of oxygen therapy, this can be limited in patients with COPD. The dressing pattern among Indian men exposes only face and feet to sunlight when involved in outdoor activities. Hence, only 23% of our study population had sufficient 25(OH)D levels, which is less than community prevalence in a healthy individual. To our knowledge, we do not know any other study from India which has reported the prevalence of vitamin D deficiency in patients with COPD. Comparing our prevalence data with Western studies would be inappropriate, as the vitamin D synthesis due to sunlight exposure depends on the solar zenith angle, minimal erythema dose, duration of sunlight exposure, and dressing pattern. 44 , 45 The limitation of our study is the small sample size which precludes the possibility of making comparison across different stages of COPD. However, this is the first study from India, to our knowledge, to assess other parameters other than BMD to examine bone health in a male patient with COPD. It may be prudent to conduct similar studies in groups of premenopausal and postmenopausal women with COPD on a separate basis to understand the profile of their bone health. 6 CONCLUSION Osteoporosis and an abnormal bone health profile is highly prevalent among patients with COPD. Differences in the patient characteristics and diagnostic tools account for the varied prevalence across studies, in any case, it is much higher than the general population. Higher prevalence of osteoporosis in the past was solely attributed to the increased glucocorticoid exposure but parameters for adverse bone health were seen even in steroid naive patients suggestive of a more complex underlying mechanism. Osteoporosis and osteoporotic fracture related morbidity and mortality will add to the already existing disease burden in those affected by COPD. But these can be prevented with proper screening and intervention, including lifestyle changes (increasing calcium intake in the diet and adequate sunlight exposure), vitamin D, calcium supplementation, and bisphosphonates when needed. This should be included in the comprehensive COPD care plan and modified to suit each individual patients' needs. AUTHOR CONTRIBUTIONS Research and study design: Jeeyavudeen, Hansdek, Thomas, Balamugesh, Gowri, and Paul. Data collection: Jeeyavudeen, Hansdek, Gowri, and Paul. Data analysis: Balamugesh, Gowri, and Paul. Interpretation and conclusion: Jeeyavudeen, Hansdek, Thomas, and Paul. Preparation of manuscript: Jeeyavudeen, Hansdek, and Paul. Review of manuscript: Jeeyavudeen, Hansdek, Thomas, Balamugesh, Gowri, and Paul. Critical revision: Jeeyavudeen, Hansdek, and Paul. Guarantors for the study: Jeeyavudeen. FUNDING INFORMATION The protocol was approved by the institutional review board (IRB) of Christian Medical College, Vellore, and the funding was provided by the FLUID grant of the IRB. There was no involvement of the funding source in study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. CONFLICT OF INTEREST The authors report no conflicts of interest for this study. ETHICAL APPROVAL This study was approved by Office of Research, Institutional Review Board, Christian Medical College, Vellore, India IRB Min No: 7996 [Dated] February 12, 2013. ACKNOWLEDGMENTS None. |
PMC10000285 | In the recycling of retired lithium-ion batteries (LIBs), the cathode materials containing valuable metals should be first separated from the current collector aluminum foil to decrease the difficulty and complexity in the subsequent metal extraction. However, strong the binding force of organic binder polyvinylidene fluoride (PVDF) prevents effective separation of cathode materials and Al foil, thus affecting metal recycling. This paper reviews the composition, property, function, and binding mechanism of PVDF, and elaborates on the separation technologies of cathode material and Al foil (e.g., physical separation, solid-phase thermochemistry, solution chemistry, and solvent chemistry) as well as the corresponding reaction behavior and transformation mechanisms of PVDF. Due to the characteristic variation of the reaction systems, the dissolution, swelling, melting, and degradation processes and mechanisms of PVDF exhibit considerable differences, posing new challenges to efficient recycling of spent LIBs worldwide. It is critical to separate cathode materials and Al foil and recycle PVDF to reduce environmental risks from the recovery of retired LIBs resources. Developing fluorine-free alternative materials and solid-state electrolytes is a potential way to mitigate PVDF pollution in the recycling of spent LIBs in the EV era. The state-of-the-art separation technologies are evaluated for cathode materials and Al foil of spent lithium-ion batteries, including physical separation, solid-phase thermochemistry, solution chemistry, and solvent chemistry, as well as the corresponding reaction behavior and transformation mechanisms of the organic binder polyvinylidene fluoride. cathode materials circular economy EV battery recycling lithium recovery sustainable waste management Hong Kong Research Grants Council15222020 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 M. Wang , K. Liu , J. Yu , Q. Zhang , Y. Zhang , M. Valix , D. C. Tsang , Challenges in Recycling Spent Lithium-Ion Batteries: Spotlight on Polyvinylidene Fluoride Removal. Global Challenges 2023, 7 , 2200237. 10.1002/gch2.202200237 pmc1 Introduction Global emissions of greenhouse gases including carbon dioxide, methane, nitrous oxide, and fluorinated gases from use of fossil fuels have increased significantly since the 1900s and today these contribute to over three-quarters of total emissions. Electric vehicles (EVs) are an important part of the mix of low-carbon energy sources that are urgently needed to mitigate global climate change. Although the trend towards the use of EVs can facilitate the reduction of greenhouse gases, there are concerns on the impact of EVs production on the ecosystems and its potential human toxicity. These impacts should be alleviated through circular economy approaches that require efficient recycling of retired battery materials. The recycling technologies for EVs batteries, however, are still in their infancy, which may pose a challenge in achieving circularity goals. The use of EVs is increasing rapidly worldwide. According to International Energy Agency (IEA), the global EV sales in 2021 were 6.6 million, which was double from the production in the previous year. The IEA predicts that by 2030 there will be over 145 million EVs in use and most if not all will be powered by lithium-ion batteries (LIBs). Considering that the service life of the battery pack is usually 6-8 years, globally this will usher in a wave of end-of-life EVs. The challenges that will be posed by the corresponding generation of huge numbers of end-of-life EVs and LIBs to the environmental protection are still unknown, but is it expected to be significant unless appropriate recycling technologies are developed. The LIBs contain toxic but valuable non-renewable metals such as lithium (Li), nickel (Ni), cobalt (Co), manganese (Mn), aluminum (Al), and copper (Cu), as well as fluorine compounds such as lithium hexafluorophosphate (LiPF6) and polyvinylidene fluoride (PVDF). If not properly recycled, end-of-life LIBs would pose health, ecological, and hazardous risks in addition to substantial wastage of valuable resources. The pollution control of organic compounds in solid waste has always been a grand challenge. Part of the challenges in recycling LIBs include the cost and the complexity of chemical features and structures that make it difficult to disassemble. The LIBs mainly include five components, i.e., shell, cathode electrode, anode electrode, separator, and organic electrolyte . The Cu foil is usually used as the substrate of the anode electrode, and the anode electrode material is evenly coated on both sides. The anode material comprises anode active material (e.g., graphite, silicon, and carbon) and cathode binder (e.g., styrene-butadiene rubber, acrylic resin, and sodium carboxymethyl cellulose). Because the anode binder is generally a water-soluble chemical, Cu foil can be separated from anode active material via ultrasonic treatment combined with water immersion. Al foil is usually used as the substrate of the cathode electrode, and the cathode material is evenly coated on both sides. The cathode material includes the cathode active material, conductive agent acetylene black, and organic binder PVDF . The cathode active material and conductive agent acetylene black are chemically bonded with current collector Al foil by PVDF . Figure 1 Structure diagrams of LIBs. a) Main components. Reproduced with permission. Copyright 2018, Elsevier. b) Internal structure. Reproduced with permission. Copyright 2022, John Wiley and Sons. c) Structure of cathode materials and Al foil (Yellow coating represents PVDF film). Reproduced with permission. Copyright 2019, American Chemical Society. The cathode active materials in LIBs are divided into lithium cobaltate (LiCoO2, LCO), lithium iron phosphate (LiFePO4, LFP), lithium manganite (LiMnO2, LMO), and ternary nickel cobalt manganese (LiNi x Co y -y O2, NCM). The main economic driver for recycling the retired LIBs is the recovery of valuable metals from cathode materials. The physical and chemical properties of valuable metals in the form of polymetallic compounds are relatively stable with lower environmental impact; their recycling is principally driven by resource utilization. In contrast, the fluorine-containing compounds in the LIBs show a higher environmental risk, especially the LiPF6 and PVDF. The International Agency for Research on Cancer (IARC) of the World Health Organization published a list of carcinogens in 2017, three of which include fluorine. Nevertheless, there are few studies of recycling organic fluorides from the retired LIBs because of their low content and economic value when compared to the valuable metals of LIBs. Thus, comprehensive research and discussion in the holistic recycling of end-of-life LIBs are incredibly urgent. Because of different chemical nature and structures of LIBs components, recycling of each part will require various technologies. An important step in recycling valuable metals from LIBs is the efficient separation of the battery components specifically the cathode material, PVDF and the Al foil. The complete separation of the cathode will ensure all the Al foil is recovered to allow its recycling by smelting. Complete removal of the PVDF will reduce potential fouling by the remaining organic film on cathode materials that could hamper the leaching efficiency of the metallic components by hydrometallurgy. In addition, the removal of Al foil will avoid its leaching and re-precipitation during the hydrometallurgical step simplifying the metal extraction step. Finally, recovery and recycling of the organic binder PVDF from LIBs will avoid its potential environmental pollution and promote green recycling of LIBs. The holistic recycling is an important step in improving the environmental performance of retired LIBs. To date, very few studies have specifically addressed the decomposition and recovery of PVDF in the field of spent LIBs recycling. As an organic fluorine product, PVDF of the spent LIBs can easily enter the environmental matrices through crushing, pyrolysis, incineration, and thermochemistry, thereby affecting the surrounding environment and human receptors. Monitoring the migration, transformation, and pollution control of PVDF during the recycling of spent LIBs will be a global challenge. To provide useful information for recycling and pollution control of retired LIBs, this review articulates the separation technologies of cathode materials and Al foil, as well as the migration and transformation mechanisms of PVDF in different processing technologies. This review aims to provide technical guidance for the global recycling community on spent LIBs, particularly concerning the fate of PVDF. 2 Composition and Binding Mechanism of PVDF 2.1 Composition and Structure Because of advantageous features including good thermal stability, high viscosity, and easy film formation, PVDF (CH2-CF2 n ) has been the most commonly used organic binder in LIBs. Its melting point is 170 degC, and the thermal decomposition temperature is about 350 degC. PVDF is a white powder-like polymer with a crystallinity of 50%. Five crystal types of PVDF (i.e., a, b, g, d, and e) have been reported so far, and a, b and g are the most common crystal types . These crystal types can convert to each other under certain conditions (e.g., heat, electric field, machine, and radiation energy). PVDF is characterized by high mechanical strength and good corrosion resistance. With a good chemical stability, PVDF is not easily corroded by acid, alkali, strong oxidants, and halogens at room temperature. Only a few chemicals, such as fuming sulphuric acid, strong alkali, and ketone, can induce swelling or partial dissolution. During the fabrication process of LIBs, the PVDF is first dissolved to colloid solution by strongly polar organic solvents such as n-methylpyrrolidone (NMP), dimethylacetamide, and dimethyl sulphoxide . Subsequently, the colloid solution is evenly mixed with the slurry and conductive agent of cathode materials, and then they are coated on the current collector Al foil. After the volatilization of organic solvent, the solidified PVDF becomes an effective medium for binding cathode materials to Al foil. Figure 2 a) Different crystal types of PVDF a, b, and g. Reproduced under the terms of the open access Creative Common CC BY license. Copyright 2019, Molecular Diversity Preservation International (MDPI). b) Application process of PVDF. Reproduced with permission. Copyright 2022, Elsevier. c) Bonding mechanism of PVDF in different LIBs. Reproduced with permission. Copyright 2021, Elsevier. 2.2 PVDF Functions As the organic binder, only a small quantity of PVDF is used in the LIBs production, accounting for 1.4-2.5% of the cost of LIBs, but it is irreplaceable. The functions of PVDF are as follows: 1) ensure the uniformity and safety of active materials for pulping; 2) bind the active materials among themselves; 3) bind the active materials to the current collector; 4) facilitate the solid electrolyte interface formation on graphite surface; and 5) improve the cycle performance, fast charge and discharge, and reduce the internal resistance of LIBs. Therefore, the PVDF not only binds the cathode material particles to Al foil, but it also enhances the electrical contact between cathode material and conductive agent as well as between cathode material and current collector, thus stabilizing the electrode structures. Simultaneously, the PVDF can buffer the expansion and shrinkage of the anode and cathode in LIBs. As a result, the PVDF plays an indispensable role in LIBs development. However, its strong bonding and high chemical stability can make disassembly difficult. Traces of PVDF in the cathode electrode will result in pollution of the residual organic fluoride in the recycling process, compromising the environmental performance of LIBs. 2.3 Mechanism of Bonding Evaluation and understanding the bonding between PVDF and cathode material/Al foil is an important step in efficient recycling of retired LIBs, which can be revealed by the simulation calculation of density functional theory and analysis of the surface of LIBs . Van der Waals force plays the main role in the intermolecular bonding. The bonding of modified PVDF is affected by two mechanisms: one involves van der Waals force that is dependent on the molecular weight of the binder, and the second is the chemical bond between PVDF and Al foil through the surface modification. The process simulation and theoretical calculation results showed that the interaction between PVDF and LiFePO4 particles was stronger than that of PVDF and Al foil in the LFP battery. In contrast, the interaction between PVDF and Li(Ni x Co y Mn1 -x-y )O2 particles in the NCM battery was weaker than that between PVDF and Al foil in the LFP battery. This is because PVDF is mainly distributed on the surface of LiFePO4 particles in the LFP battery, while PVDF is evenly distributed both on the Al foil and Li(Ni x Co y Mn 1-x-y )O2 particles in the NCM battery. In addition, there is no chemical interaction among cathode materials, PVDF, and Al foil. The results mentioned above showed significant differences in the distribution, binding force, and action mechanism of PVDF for different cathode materials, implying that the separation efficiency for different LIBs would be considerably different even with the same separation technology. 2.4 Current Techniques for Quantification and Identification of PVDF The quantity of PVDF accounts for about 1-2 wt.% of that of cathode electrodes. Most of the previous studies focused on the development of qualitative techniques. Because PVDF is a highly amorphous polymer, the corresponding diffraction peak in cathode electrode cannot be detected by X-ray diffraction. However, CH2-CF2 n characteristic peak can be detected in the C 1s and F 1s high-resolution energy spectra using the X-ray photoelectron technology, allowing the transformation of organic fluorine categories to be identified before and after separation reaction. In terms of the quantitative analysis of organic fluorine, there is still a lack of precise strategy. The scanning electron microscopy-X-ray energy dispersive analysis technology was used for the semi-quantitative analysis of fluorine element on the surface of the cathode electrode. Oxygen bomb combustion combined with ion chromatography can be a more accurate technology for organic halogen analysis. The steps are as follows: first, the halogen-containing solid material is put into a Teflon-alloy tank with an alkaline absorption liquid at the bottom and sealed. Subsequently, the tank is filled with pure oxygen at a certain pressure from the gas bottle. The pure oxygen in the sealed tank is ignited in a calorimeter, and the content of inorganic halogen ions in the alkaline absorption solution at the bottom of the tank is measured by ion chromatography. 3 Different Technical Systems for the Separation of Cathode Materials and Al Foil Due to differences in the design of battery recycling routes, the disposal of PVDF and the associated environmental impact are significantly different. Industrial recycling process of retired LIBs involves physical crushing/screening and heat treatment. Technologies in the laboratory stage include solvent dissolution, that is, NMP, for preserving the crystals in the cathode material and preparing for metal recovery or regeneration. Emerging technologies include pyrolysis, molten salt, electrochemistry, and supercritical fluid. The key technical principles involved in the separation and recycling of cathode material and Al foil can be divided into physical separation, solid-phase thermochemistry, solution chemistry, and solvent chemistry according to different reaction media. The separation principle and general parameters of different systems are shown in Figure 3 . Figure 3 Principles of different systems for the separation of the cathode materials from Al foil. 3.1 Physical Separation 3.1.1 Crushing and Sorting Mechanical crushing and sorting refer to directly destroying the metal shell of the spent battery by external crushing force, and at the same time assisting in the separation and enrichment of electrode materials by physical methods, such as magnetic separation and gravity screening, to facilitate the subsequent pyrometallurgical or hydrometallurgical recovery of metals and non-metallic materials. At present, this technology is widely used in engineering practice and realizes the large-scale recycling and processing of spent LIBs. Separation occurs when the cathode electrode is subjected to mechanical forces in equipment such as a universal pulverizer or an impact/shear crusher. In LIBs, the Al foil provides flexibility and crimp elasticity. The cathode particles are evenly coated on the Al foil with PVDF as the organic binder in between to provide material stiffness. When subjected to mechanical force from a crushing action, the Al foil is sheared, inducing it to curl and allowing it to be physically separated from the cathode particles. As cathode materials are particulates, they can be separated from the curled Al foil by sieving or sorting through a mesh. Smelting, by contrast, directly transforms the Al foil into a recycled product. Zhang et al. discovered a selective physical crushing of each component of LCO batteries: under the crushing effects of both shear and impact crushers, the metal shell was enriched in the > 2 mm particle size; the separator, Cu foil, and Al foil were abundantly accumulated in the < 2 + 0.075 mm particle size; while the < 0.075 mm particle size contained the cathode/anode material particles with graphite . Figure 4 Tracing PVDF in the process of dismantling-crushing-grinding-flotation of spent LIBs. Georgi-Maschler et al. used a ball mill and a disintegrator successively to crush the discharged spent LIBs. The milled material was classified and sorted through a vibrating screen, a drum separator, and a zigzag classifier. This process produced three types of metal-containing material products: Fe-Ni fraction, Al fraction, and electrode foil fraction. The finely mixed electrode materials of the LMO battery can be obtained by mechanical crushing and component sieving. Then X-ray diffraction and other techniques can be used to characterize the material compositions and properties, providing theoretical support for the subsequent carbothermal reduction process of mixed electrode materials. In addition, ultrasonic washing has been used to assist in the post-mechanical LIB crushing step and improve the separation efficiency of cathode material LiCoO2 and Al foil. The spent LIBs were first crushed and sieved, and the recovered materials were washed in an ultrasonic washing container with stirring. The pressure generated by the cavitation effect of the ultrasonic wave destroys the insoluble substances and disperses them in water during the washing procedure. This allows a 100% removal efficiency of cathode material from the Al foil. Moreover, the flushing effect of the agitation facilitates the separation process, reducing energy consumption and environmental pollution. The organic film (PVDF) attached to the surface of cathode materials after the mechanical crushing and sieving form a hydrophobic organic film that is difficult to remove by traditional flotation methods. As shown, the PVDF continues to adhere to the surface of the cathode material particles or the Al foil after mechanical separation, grinding, and flotation, suggesting that there was no decomposition or dissolution of the PVDF. Hence, the environmental impact and risks of LIB recycling will need to be considered in subsequent processing. 3.1.2 Cryogenic Grinding In general, grinding at room temperature fails to separate the cathode material from the Al foil and tends to cause pulverization of the latter. According to Liu et al., the glass transition temperature (T g) of PVDF is approximately 235 K. The use of low-temperature treatment can disrupt the microstructure of the cathode electrode, resulting in cracks and the layering of different sizes, which could largely enhance the detachment efficiency of the cathode material in cryogenic grinding. Consequently, the efficiency increased from 25.0 wt.% at room temperature to 87.3 wt.% after low-temperature grinding of the cathode electrode. Metals with face-centered cubic lattices, such as Al, reveal good mechanical properties at low temperatures. In addition, the dramatic difference in particle size permits the crushed products to be separated by a simple sieving operation. The above results demonstrate that despite the general feasibility of the physical separation of cathode material particles and Al foil by a mechanical-physical method, the following processing issues need to be further addressed. 1) The strong bonding effect of organic binder PVDF results in inefficient release of the cathode material by mechanical-physical methods. After physical crushing and sieving, a small number of the cathode material particles continued to adhere on the surface of the Al foil, causing quality loss and additional challenges in Al foil smelting. Therefore, to improve the efficiency of subsequent hydrometallurgy, the calcination of cathode material powder to remove PVDF is essential. 2) The superior chemical stability of PVDF on the surface of the cathode material particles after separation may induce negative impact on the environment and ecology, which should be considered in the subsequent metal recycling. 3) The cross-contamination of crushed Al chips with cathode material particles needs to be addressed, particularly when prolonged crushing or excessive milling speed are used. The high content of Al adversely affects the extraction and separation of metals in the follow-up hydrometallurgy. Therefore, controlling the crushing time is crucial for achieving efficient hydrometallurgical extraction of the target metallic fractions. 3.2 Solid Phase Thermochemistry Solid phase thermochemistry refers to melting or degrading PVDF in the cathode electrode by high-temperature thermochemical reaction. Thermal treatment in an oxygen atmosphere is called calcination or incineration, while thermal treatment in an oxygen-free or inert gas atmosphere is viewed as a pyrolysis process. Direct calcination of PVDF can easily cause the emission of pollutants, while a fully enclosed environment for the pyrolysis process can better control and treat the polluting gases. Specifically, this method can directly pyrolyze and convert PVDF into pyrolytic oil, gas, and hydrogen fluoride (HF). Meanwhile, alkaline catalyst can accelerate catalytic degradation of PVDF and enable in-situ capture of inorganic fluoride. To eliminate the generation of dioxins, ammonia injection was considered as an effective strategy for high-temperature dehalogenation. Apart from direct and catalytic pyrolysis, new technological approaches, such as molten salt-mediated treatment and pulsed high-voltage discharge, can achieve the melting or degradation of PVDF in solid thermal media, detaching the cathode material from the Al foil and preventing the release of fluoride . Figure 5 Degradation products and occurrence forms of PVDF in solid phase thermochemical media at different temperatures. 3.2.1 Calcination/Pyrolysis Pyrolysis enables the decomposition of PVDF by placing the cathode electrode into a high-temperature incinerator or rotary kiln under inert gas protection, achieving separation between cathode materials and Al foil. Table 1 summarizes the current heating processes for cathode materials and Al foil separation. It should be noted that the melting point and thermal decomposition temperature of PVDF are approximately 160 and 300 degC, respectively; hence high-temperature treatment is a convenient and efficient method for the separation of LIB components. Table 1 Thermochemical processes for separation of cathode materials and Al foil Process Samples Atmosphere Reaction Conditions Separation Percentage Products References Calcination NCM Air 450degC, 2 h 100% Li(Ni1/3Co1/3Mn1/3)O2 NCM Air 500degC, 1.5 h 97.1% LiNi0.33Mn0.33Co0.33O2 NCM Air 600degC, 5 h 100% Li(Ni1/3Co1/3Mn1/3)O2/C LFP Air 600degC, 1 h 100% Li3Fe2(PO4)3/Fe2O3 Cathode mixture Air 300degC, 1 h, then 550degC, 0.5 h 100% LiCoO2/Co3O4/Li4Mn5O12/Li0.9Ni0.5Co0.5O2-x Cathode mixture Air 550degC, 1.5 h 99.01% LiCoO2/LiNiO2/LiMn2O4 Pyrolysis LFP N2 500degC, 0.5 h 96.86% LiFePO4/C NCM N2 600degC, 15 min 100% Li(Ni1/3Co1/3Mn1/3)O2 LFP N2 550degC, 2 h 99.34% LiFePO4/C/Al LCO N2 500degC, 15 min 98.23% LiCoO2/C NCM N2 450degC, 0.5 h 100% Li(Ni1/3Co1/3Mn1/3)O2/Al Cathode mixture N2 550degC, 1.5 h 97.90% LiCoO2/LiNiO2/LiMn2O4 Vacuum Pyrolysis LCO <1.0 kPa 600degC, 0.5 h 100% LiCoO2, CoO, and Al foil LCO Vacuum 600degC, 3 h 100% Cathode powder, and Al, Cu and Ni, etc. LCO Vacuum 500degC, 15 s 99.78% LiCoO2/C LCO N2, Vacuum 500degC, 0.5 h 100% LiCoO2/C NCM 1000Pa 600degC, 0.5 h 98.04% LiNixCoyMn1-x-yO2/NiO2 LCO Vacuum 673 to 723 K, 1 h 100% LiCoO2, CoO, and Al foil LFP 1000 Pa 600degC,0.5 h 100% LiFePO4/C Cathode mixture N2, Vacuum 650degC, 1.5 h 97.90% Li2CO3/Mn3O4/Co3O4/NiO John Wiley & Sons, Ltd. Research results showed that PVDF in the cathode electrode initially decomposed at a heating temperature of 380 to 400 degC. At 600 to 700 degC, the conductive additive reacted with oxygen by combustion, at which the Al foil melted (melting point of 660 degC). Another study showed that when fragments of a waste LCO battery were placed in a vacuum heating chamber at 600 degC, the PVDF achieved complete pyrolysis after heating for 30 min, but the conductive additive did not combust. As the heating temperature failed to meet the standard of decomposition of cathode materials, the LiCoO2 crystal and the conductive additive could not realize complete shedding from the Al foil. Christian et al. examined the pyrolysis rate of PVDF at different temperatures and found that PVDF began to decompose at 350 degC, reached a weight loss of 98.9 wt.% at 550 degC, and totally decomposed at 580 degC. Thus, the optimal pyrolysis interval for PVDF is 500-580 degC. Furthermore, the experimental results confirmed that the ideal pyrolysis temperature for the organic binder in the electrode material was 500 degC, and the primary pyrolysis products were fluorobenzene, hydrocarbon, and ester. Upon pyrolysis, the release efficiencies of the cathode material rose from 82.9 to 99.8 wt.%. Other research has also confirmed that the electrolyte was the primary source of the fluorine-containing gases, and that HF was released during the pyrolysis of the spent LIBs. The PVDF binder decomposed into H2O, CO2, and fluorine-containing gases, with the largest peak detected at 522 degC. Moreover, Liu et al. investigated high-temperature separation of the cathode electrode in a retired LFP battery and carried out a kinetic study of the pyrolysis process, employing the iso-conversional method. The results revealed that the average pyrolysis activation energy of the cathode electrode was 85.36 kJ mol-1, which depended on the temperature zone. Under nitrogen protection, 50 wt.% of the PVDF decomposed and was converted to pyrolysis gas and oil phase at about 475 degC, whose main components were HF and light hydrocarbons, and the HF gases could be absorbed by alkaline solution. Furthermore, graphite and LiFePO4 crystals retained their material and structural integrity under this condition. Huang et al. proposed that the co-pyrolysis of electrolytes, PVDF, and active materials exhibited significant adverse synergistic effects. In the co-pyrolysis process, active materials adsorbed the electrolyte residues on the surface and into the pores (20-200 degC), while PVDF formed a liquid film that covered the local surface of the active materials (400-500 degC). These interactions prevented the efficient removal of organics, leaving fluorine-containing contaminants in the active materials. Enhancing the pyrolysis temperature can facilitate the removal of organics. These recent studies have shown that a degradation temperature ca. 500 degC is relatively reliable for PVDF degradation. In this process, the production of fluorine-containing organics such as fluorobenzene and hydrocarbons was detected. These fluorinated organic pollutants are a potential source of environmental pollution and a risk factor in applying pyrolysis technology. Differences in thermochemical strategies may affect the compositions and pathways of the degradation products of PVDF. However, relevant research is still insufficient. To eliminate the negative environmental impact of PVDF in the thermochemical reaction, calcium oxide (CaO) was used as an alkaline defluorination medium. The results concluded that PVDF in the cathode electrode could undergo catalytic pyrolysis and de-fluoridation at a temperature of 300 degC. The pyrolysis oil-phase products were hydrocarbons, and the pyrolytic gas was hydrogen. The carbon dioxide attained in situ adsorption and immobilization by CaO. The released HF gas was converted to calcium fluoride by CaO. The separation efficiency of the cathode material from the Al foil under optimal conditions exceeded 97.1 wt.%. Consequently, the employment of CaO not only reduced the energy consumption but also averted the release of HF, presenting both economic and environmental benefits. 3.2.2 Molten Salt-Mediated Treatment Molten salt is a liquid reaction medium formed by heating an ordinary solid inorganic salt above its melting point (e.g., NaNO3 melts at 308 degC, NaCl melts at 801 degC), followed by a series of physical and chemical reactions including heat storage, oxidation, and electrolysis, utilizing its properties as a thermal medium. As an anhydrous high-temperature flux, the main feature of molten salt is its dissociation into ions when melted, and the positive and negative ions are bound together by Coulombic forces, making it available as a thermal reaction medium at high temperatures. Considering the advantages of molten salt, such as a wide range of operating temperature, high thermal conductivity, low working pressure, and low material cost, it has been broadly studied in the field of solid waste treatment. A low-temperature molten salt, an AlCl3/NaCl molten salt system, was first proposed for separating spent cathode materials and Al foil. The findings showed that the AlCl3/NaCl molten salt system allowed for efficient and rapid melting of PVDF, compared to KNO3/NaNO3 or KOH/NaOH molten salt. The former held a melting point of 153 degC, and its phase transition from solid to liquid absorbed a large amount of heat, resulting in the melting of PVDF. When the temperature fell to room temperature, the heat stored in the AlCl3/NaCl molten salt was released, and the medium reverted to the solid state. The phase transition repeatedly circulated to a heat storage and release cycle, which was repeated as necessary, to separate the cathode materials and Al foil. The optimum separation conditions were temperature of 160 degC, holding heating time of 20 min, and mass ratio of molten salt/cathode electrode of 10:1. In this process, the highest percentage of detachment of Al foil that could be achieved was over 99.8 wt.%. After molten salt treatment, the organic fluorine species adhering to the surface of the cathode materials remained in the form of PVDF. Therefore, the high-temperature melting of PVDF is considered to be the reason for the separation of Al foil and cathode materials. Ji et al. studied the separation efficiency of binary eutectic systems of three common inorganic lithium compounds -- LiCl, LiOH, and LiNO3 -- on cathode materials and Al foil. Among the three binary mixtures, LiNO3-LiOH exhibited the best detachment performance. The cathode materials (NCM111 and LiMO) achieved a detachment efficiency of 98.3 wt.% with Al foil at a LiNO3-LiOH molar ratio of 2:3, temperature of 260 degC, duration of 30 min, and salt-to-cathode mass ratio of 10:1. As for the other cathode electrodes -- LCO and LFP -- the detachment efficiencies of LiNO3-LiOH were 95.7 and 87.8 wt.%, respectively. Current studies indicate that since the melting point of PVDF is 160 degC, the range of molten salt utilization is between 160 and 300 degC, which is much lower than the complete thermal decomposition temperature of PVDF (400-500 degC). Molten salt separation presents significant environmental benefits such as low energy consumption, low reagent cost, free discharge of wastewater, and excellent recyclability. To date, reports on molten salt exfoliation of cathode electrode sheets are limited. Depending on the molten salt system, the separation mechanisms of Al foil and cathode materials differ considerably. Overall, at a low temperature (160 degC), PVDF melting is believed to be the cause of the exfoliation of the cathode materials, while at a relatively high temperature (300 degC), if an alkaline medium exists, the PVDF is likely to be degraded through the nucleophilic substitution of alkaline groups, resulting in the separation of cathode materials and Al foil. Considering its environmentally friendly properties and relatively low operating temperature, the molten salt process is deemed as a new detaching technology for battery cathode electrode with promising industrial application. 3.2.3 High-Voltage Pulse High-voltage pulse takes advantage of pulsed power technology to emit massive amounts of energy over a brief period, dissociating metallic conductive materials from non-metallic non-conductive materials in solid materials. This technology has successfully separated metallic and non-metallic composites in urban minerals. Motivated by the conductivity of Al foil and the non-conductivity of cathode material particles/graphite, a novel electrical method for separating cathode materials and Al foil, based on pulsed high-voltage discharge, was developed. First, the cathode material was cut into a 30 mm x 80 mm test sheet and discharged with a high-voltage electric pulse, using water as a protective medium. At a voltage of 25 kV, 93.9 wt.% of the cathode material particles were separated from the Al foil. The Al foil remained intact after separation, and the cathode material particles could be recovered after sieving through a 2.36 mm mesh. As per the mechanistic analysis, the PVDF binder in the cathode material particle layer melted and lost adhesion by Joule heating of the Al foil under the action of electric current, while the recovered cathode particles maintained their chemical composition and shape after separation. In addition, life cycle assessment revealed the potential to reduce greenhouse gas emissions and resource consumption by recovering cathode material particles and Al foil from cathode electrodes through pulsed discharge when the disposal scale was sufficiently large. Overall, the technology is simple and effective, providing rapid separation of the cathode material from the Al foil, thereby obviating the risk of environmental contaminant releases. Thermal treatment has application advantages including the simplicity of the process, ease of operation, and extensive scale-up options. By adjusting the temperature interval and selecting the reaction medium, the method allows for adjustable melting or decomposition of PVDF, making it the most popular choice for separating cathode materials and Al foil in recovering retired power LIBs. In industrial application, high-temperature pyrolysis is the most mature and straightforward method for batch treatment of the PVDF remaining on the surface of cathode material particles after physical sorting. However, the pyrolysis process can release HF gases, leading to noticeable challenges, including atmospheric pollution, volatilization of active Li, and equipment corrosion. Although alkali absorption tackles the exhaust pollution, the intense corrosiveness of inorganic fluoride tends to shorten the working life inside high-temperature treatment equipment and increases recovery costs. Moreover, dioxin, a derivative of organic fluoride, would incur latent environmental hazards. From the perspective of battery classification, for a retired LFP battery, the high energy consumption of heat treatment often squeezes the profit margin of the Li extraction while increasing carbon emissions, resulting in an unprofitable LFP battery recycling situation. The high carbon emissions also counteract the original intention of promoting new EVs. Therefore, high-temperature treatment is not a sustainable route for the recycling of spent LFP batteries. The concomitant separation of cathode materials and Al foil via the hydrometallurgical route appears to be more cost-effective and low-carbon. For LCO and NCM batteries, corrosive-resistant materials should be substantially developed for practical heat recovery, along with tail gas-absorption devices to strictly control the amount and concentration of fluoride releases and to closely monitor the dioxins to prevent secondary pollution. 3.3 Solution Chemistry Regulating the solution chemistry conditions in an aqueous environment can efficiently separate cathode materials from Al foil. There are various ways to meet this objective, including acid/base/oxidative dissolution, Fenton oxidation, electrolysis, and ultrasonic cleaning . These processes proceed in aqueous solutions, but the separation mechanisms vary. Acid dissolution enables separation by moderating the acidity of the solution to dissolve the cathode material particles and leach Li to weaken the chemical bonding of the PVDF. Alkali dissolution realizes the detachment of cathode material particles by selective dissolution of Al foil. Fenton oxidation involves depolymerizing PVDF molecules by free radical reaction, accomplishing material separation. Ultrasonic cleaning utilizes material vibration triggered by the cavitation effect to weaken the adhesion between cathode materials and Al foil. Figure 6 Mechanisms and reactive species of separation of cathode material and Al foil with different solution systems. 3.3.1 Acid/Base/Oxidative Separation Acid/base/oxidative dissolution implemented in an aqueous solution does not affect organic polymer PVDF but separates the cathode material and the Al foil by different mechanisms. The base system consists of selective dissolution of the Al foil, because the cathode material particles (LCO and NCM) generally do not react with the alkaline solution, while the current collector Al foil does. NaOH (5 wt.%) is used as the dissolving solution for the Al foil of the cathode electrode. Almost all the Al foil dissolves in the alkaline solution at room temperature, while cathode material powder is obtained after filtration. The acid dissolution method aims to directly dissolve all the valuable metals in the cathode material, such as Li, Ni, Co, and Mn, in an acidic solution, followed by solvent extraction or fractional precipitation to separate and recover the different metals. During this process, high acid concentration will cause the dissolution of the Al foil. Given the above process defects, organic trifluoroacetic acid (TFA) was adopted as a leaching reagent to separate cathode materials and Al foil in the waste LIBs. Under the optimal conditions of 15 vol.% of TFA solution, L/S ratio of 8.0 mL g-1, temperature of 40 degC, and time of 180 min, the Li could be selectively leached, weakening the bonding of the PVDF to the crystal. The Al foil prevented the corrosion and dissolution of the TFA. As a result, complete separation of cathode material and Al foil was achieved. In this recycling process, PVDF is considered to still exist on the surface of the cathode material after hydrometallurgical leaching. These organic binders can be removed by calcination at the temperature of 700 degC. As outlined in Section 2.4, the mechanisms of action of PVDF differ markedly among the different cathode electrode types. Compared to NCM and LCO crystals, PVDF interacts more feebly with Al foil in the LFP cathode electrode. Accordingly, automatic separation of the C/FePO4 residue from the Al foil has been developed using a feasible design process after selective Li extraction. Yang et al. suggested a route for selective leaching of Li from retired LFP batteries by regulating the proton acid concentration and separating out the Al foil. The Al foil stayed undissolved into the liquid phase with reasonable control of the proton acid concentration in the acetic acid solution. At the same time, the Li in the LiFePO4 could be selectively extracted, owing to the mosaic effect of the Li in the olivine structure of the FePO4. After selective leaching of Li, the C/FePO4 residue was separated from the Al foil. Zhang et al. confirmed that after the Li in the retired LFP battery was extracted by oxidation, the bond between the C/FePO4 residue and the Al foil decreased, thus enabling the residue separation from the intact Al foil. In the hydrometallurgy process, PVDF was located on the surface of graphite residue and FePO4 skeleton, and only an amount of inorganic fluorides entered the leaching solution in the form of lithium fluoride. The separation of cathode materials and Al foil by acid/base/oxidative dissolution consumes considerable amounts of concentrated alkali or acid and generates a massive quantity of wastewater, adding to the recovery cost. In practical hydrometallurgy, dissolving Al foil into the liquid phase before precipitation separation is not a preferable approach. The aqueous solution separation method requires high corrosion protection for the equipment and causes the dissolution of highly reactive Li, rendering it impractical for large-scale batch processing. The development of organic acids has relieved the environmental pressure and burden, yet these acids are expensive. Furthermore, mixed types of metals introduced into the liquid phase will require tedious subsequent metal separation steps. 3.3.2 Fenton Oxidation Fenton oxidation adopts hydrogen peroxide (H2O2) and ferrous (Fe2+) reagents to generate hydroxide radicals in a chemical reaction to obtain the oxidative degradation of organic pollutants. This method has been broadly applied to the decomposition of organic matter in the atmosphere and soil. Following physical and mechanical crushing, PVDF remains attached to the surface of cathode material particles and graphite particles and forms a hydrophobic organic membrane. Traditional methods struggle to effectively separate cathode materials and graphite, creating an obstacle for subsequent metal recovery. As PVDF is essentially a linear polymer with simple chemical composition and structure, Fenton oxidation could be applied to degrade PVDF on the surface of LCO cathode materials and graphite into water-soluble inorganic fluorine, phosphate, carbonate, and other small-molecule organic compounds, which solved the surface residue problem of PVDF in an efficient and eco-friendly way. However, this method is applicable for dealing with a small volume, and costs more for reagents. Introducing impurities such as iron into the system potentially creates unfavorable interfering factors for the subsequent hydrometallurgical extraction of the critical metals. The above considerations account for the limited extent of practical application of Fenton oxidation in the decomposition and recovery of PVDF. For spent LFP battery recycling, Fenton oxidation stripping may be more suitable. Wu et al. used the Fe2+ in waste LiFePO4 crystal to induce an in-situ Fenton reaction, developed a green and economical H2O2 system, and realized the complete recycling of waste LFP batteries. The optimal conditions were H2O2 concentration of 0.2%, rotation speed of 400 rpm, reaction time of 4 min, and solid-liquid ratio of 14.2 g L-1. The loss of Al foil was less than 0.4 wt.%. The success of this application could be attributed to the weaker binding force of PVDF to Al foil in the LFP cathode electrode (as described in Section 2.3). Mechanistic analysis demonstrates that in a Fenton system, hydroxyl radicals can rapidly oxidize part of the PVDF, thereby reducing the binding energy between PVDF and Al foil and weakening the molecular binding force between Al foil and cathode materials. According to He et al., the degradation products of PVDF after Fenton or electrolytic oxidation were likely to be small molecules. Compared to traditional methods, Fenton oxidation system has the advantages of zero acid, zero base, or zero organic solvent usage and mild stripping conditions. However, the feasibility of this method for separating NCM and LCO batteries is questionable. 3.3.3 Electrochemistry Electrochemistry describes the process of separating cathode materials from Al foil through a chemical reaction in the presence of an applied current. Similar to Fenton oxidation, electrochemistry may be more applicable to the peeling of cathode materials from Al foil of LFP batteries due to the relatively weak binding force between PVDF and Al foil. In an electrochemical oxidation technique designed by Wu et al., only 3 g L-1 sodium sulfate was used as the electrolyte, the LFP cathode material could be completely oxidized and stripped within 15 min under the electrolysis voltage of 10 V. Morphology and crystal structure analysis showed that the LFP cathode material was completely exfoliated, the Al foil was clean, and there was no corrosion. Considering the complexity of the cathode electrode, electrolytic separation is not a technology targeted at separation; instead, it serves to accompany the recovery of metal compounds. As for advantages, it enables the separation to obtain pure Al foil and induces electrolytic conversion of partial cathode material to ionic form for the follow-up precipitation step. Nevertheless, the disadvantage lies in the thicker coating of cathode material particles on the Al foil surface, which may cause low electrolysis efficiency. The heavy electricity consumption also incurs high cost. 3.3.4 Ultrasonic Cleaning Ultrasonic propagation can vibrate the media molecules and lead to a cavitation effect through bubbles, weakening the bond between the cathode material and the Al foil and thus achieving separation. However, direct sonication of the cathode electrode proves to be exceedingly difficult for achieving detachment for LFP batteries. Auxiliary solution media, such as LiOH solution, inorganic acid, organic acid, Fenton reagent, and organic solvent, are essential to attenuate the adhesion of the organic binder. The detachment efficiency can be improved dramatically with acidic solutions (sulphuric acid and oxalic acid) as the media. Approximately 99, 100, and 46 wt.% of the coating cathode material could be separated in sulphuric acid, oxalic acid, and pure water media, respectively, yielding Al foil with corresponding purities of 98, 99, and 15 wt.%. A plausible explanation for this accomplishment could be the strong oxidation of HO* radicals formed in the acidic ultrasonic solution leading to the quick degradation of the adhesive. In summary, this approach enhances the detachment efficiency and product purity of the cathode materials and Al foil, presenting an alternative solution for the recovery of retired LIBs. Hydrometallurgy remains the dominant technology for metal recovery from the cathode materials, followed by solution chemistry, which is a highly effective method for separating cathode material from Al foil and degrading PVDF. The tunability is the advantage of applying a solution chemical system for separating cathode materials and Al foil. That is, by choosing a suitable acid, alkali, or oxidation system, dissolution of the Al foil, leaching of metals, and/or selective recovery of Li can be flexibly achieved. However, solution chemistry is not currently a prevailing separation strategy for the following reasons: 1) possible dissolution of Al foil during the separation process prolongs the metal recovery and poses impurity separation challenges; 2) generation of acid/alkali wastewater boosts reagent consumption and metal recovery costs; and 3) crystalline compounds may undergo corrosion in solution chemistry, entailing the loss of valuable metals. 3.4 Solvent Chemistry Due to the release of organic fluorides and the possible formation of dioxins, thermochemical defluorination is a less-than-perfect response to the challenge of separating cathode materials from Al foil. In contrast, solvent chemistry is likely to be a greener and more environmentally friendly measure. Compared with direct high-temperature thermal treatment, solvent chemistry decomposes PVDF under milder reaction conditions, i.e., 20-200 degC, and consumes relatively less energy. Secondly, solvent chemistry can address the problem of the release of organic fluoride. The decomposition of PVDF encompasses the recovery or removal of organic solvents, ionic liquids (ILs), deep eutectic solvents (DESs), or bio-based solvents, and includes supercritical fluid extraction (Table 2 ). Table 2 Solvent processes for separation of cathode materials and Al foil Solvents Cathode materials Reaction Conditions Separation percentage Products References Organic solvents N-methyl-2-pyrrolidone LCO Room temperature, ultrasonic treatment, 3 min 99% Al foil, C, LiCoO2 N, N-dimethylformamide LCO 60degC, 2 h 100% Al foil, C, PVDF, LiCoO2 Dimethylacetamide NCM 84degC, 5 min 97% Al foil, C, PVDF, LiNi1/3Co1/3Mn1/3O2 Ethylene glycol NCM S/L mass ratio = 1:10, 160degC, 6 s 100% Al foil, C, PVDF, LiNi0.5Mn0.3Co0.2O2 Triethyl phosphate NCM S/L mass ratio = 1:10, 100degC, 1 h 100% Al foil, C, PVDF, LiNi0.6Mn0.2Co0.2O2 Cyrene NCM S/L ratio = 500 g L-1, 100degC, 1 h 100% Al foil, C, PVDF, LiNi0.6Mn0.2Co 0.2O2 Dimethyl isosorbide Cathode electrode mixture S/L ratio = 1:40 g mL-1, 150degC, 5 h 100% Al foil, cathode materials Glycerin NCM 200degC, 350 r min-1, 15 min 95% Al foil, C, PVDF, LiNi0.5Co0.2Mn0.3O2 IL 1-Butyl-3-methyl-imidazolium-tetrafluoroborate LCO 300 r min-1, 180degC, 25 min 99% Al foil, C, PVDF, LiCoO2 DES Choline chloride-glycerol DES NCM 190degC, 15 min 99.86% Al foil, C, PVDF, Li(NiCoMn)1/3O2 Potassium carbonate-ethylene glycol DES LFP S/L mass ratio = 1:20-25, 100degC, 20 min 99.3% Al foil, C, PVDF, LiFePO4 Biological solvents Citrus juice LCO S/L ratio = 50 g L-1, 90degC, 20 min 100% C, Al, LiCoO2, Co3O4 Waste oil-based fatty acid methyl esters LFP 190degC, 20 min 99.1% Al foil, C, PVDF, LiFePO4 Supercritical fluid Supercritical CO2 LCO 10 MPa, 38 degC, 15 min 98.86% Al foil, C, LiCoO2 Supercritical CO2 & dimethyl sulfoxide NCM 8 MPa, 70 degC, 13 min 98.5% Al foil, C, Li(NiCoMn)1/3O2 John Wiley & Sons, Ltd. 3.4.1 Organic Solvents In LIB production, the intensive polar solvent NMP is generally preferred for dissolving PVDF, followed by homogeneous mixing of the dissolved PVDF solution with cathode materials to coat the binder and the cathode material in the Al foil. Hence, according to the principle of "similar miscibility", organic solvents with strong polarity can effectively dissolve or swell PVDF for cathode material separation and Al foil recovery. The solubility of PVDF in three selected organic solvents (N-dimethylformamide (DMF), N-dimethylacetamide (DMAC), and NMP) was found to be positively correlated with temperature. When the temperature reached 70 degC, the solubilities of PVDF in DMAC, NMP, and DMF were 214, 216, and 176 g L-1, respectively. The cathode material and Al foil could then be completely separated and recovered. The dissolution effects of four different organic solvents (DMAC, NMP, DMF, and dimethyl sulfoxide (DMSO)) on PVDF in the cathode electrode of a retired NCM battery were compared, and the results showed that DMAC, which is low-toxic, environmentally friendly and cost-effective, could achieve the optimal separation. After processing at 60 degC for 85 min, clean and bright Al foil was obtained and applied directly in smelting. The dissolution of PVDF in NMP cleaning solution, followed by ultrasonic cavitation, efficiently separated the cathode material from the Al foil, with a simultaneously decreasing agglomeration of the cathode material particles, which facilitated the subsequent leaching process. Despite the relatively effective adoption of organic solvents to dissolve PVDF and their frequent application in the laboratory stage, the use of organic solvents--particularly at a large scale--needs to consider hazard risks because of their volatility and high toxicity, which can pose substantial hazards to occupational health and the environment. Accordingly, to weaken the potential toxicity of solvent chemistry, He et al. developed an exfoliating extract whereby the cathode material could be detached from the Al foil by weakening the mechanical interlocking force and the Coulombic force between them. The recovery rates of electrolyte, Al foil, Cu foil, and cathode materials were 95.6, 99.0, 100, and 100 wt.%, respectively. As a result, the exfoliating extract effectively prevented impurities from penetrating cathode materials. However, the ingredients of the exfoliating liquid have so far not been disclosed due to patent protection. Some new and low-toxic organic solvent systems, such as ethylene glycol, triethyl phosphate, cyrene, and dimethyl isosorbide, have been developed for the separation of cathode materials and Al foil. In the reports published so far, there is still no consensus on the separation mechanisms of cathode materials and Al foil in these organic solvent systems. Overall, the dissolution mechanism of PVDF in dimethyl isosorbide proposed by Buken et al. can be referred to. PVDF adheres to the current collector Al foil through hydrogen bonds. The rapid dissolution of PVDF in organic solvents can be attributed to the following steps: i) dimethyl isosorbide first penetrates the PVDF crystalline region to reduce the PVDF polymer chain interactions, ii) dimethyl isosorbide interacts with hydrogen and fluorine atoms in PVDF and establishes hydrogen bonds to enhance solvent-polymer interactions; iii) dimethyl isosorbide actively participates in the formation of hydrogen bonds in the thin oxide layer of the alumina coating of the current collector, thereby weakening the PVDF adhesion in the Al foil and promoting the swelling and partial dissolution of PVDF, thus effective separation of cathode materials. However, the potential environmental toxicity of the organic solvents is an unavoidable and hidden danger in practical application. The expensive and toxic organic solvents also increase the recovery costs. Therefore, the separation of cathode materials by organic solvents remains at the laboratory stage and fits small-scale processing or material regeneration rather than large-scale industrial application. 3.4.2 Ionic Liquids Inorganic or organic anions and cations constitute ILs, which are solvents containing ions with properties of high electrical conductivity, low melting point, superior thermal stability, and outstanding solubility. ILs in various structural forms composed of different anions and cations can dissolve many organic and inorganic compounds, polymeric materials, etc. The imidazolium IL was first used to address the challenge of separating the cathode material and Al foil in the retired LIBs. The detachment rate of the cathode material was low as the temperature fell below 165 degC (speed of 300 rpm and duration of 20 min). Given that 165 degC is lower than the melting temperature of PVDF, the small amount of detachment likely came from damage by the mechanical forces of the mixer. Thus, the most favorable separation temperature was determined to be 180 degC, and the reaction of the cathode electrode in the imidazolium IL was considered to be the dissolution of PVDF. There have been numerous reports on applying ILs to e-waste. Apart from tackling the separation of waste LIB cathode materials and Al foil, researchers studying the recycling of waste printed circuit boards, fluorescent powder, and so on have observed the success of exploiting ILs. However, the high fluid viscosity makes ILs prone to adhesion on the surface of cathode materials, resulting in mass loss. Due to the high synthesis cost of ILs, the recovery expense is likely to increase. Moreover, the potential adverse impact of ILs as reaction media on the ecological environment remains unclear, representing a practical obstacle for ILs to be promoted in the industrialization of spent LIB recycling. 3.4.3 Deep Eutectic Solvents The high cost, sophisticated synthesis steps, and potential biological toxicity may limit broad application of ILs. In this regard, there is a direct need to develop cost-effective, efficient, and minimally toxic green solvent systems to degrade PVDF in the retired LIBs. Compared with ILs, inexpensive and broadly available DESs are preferred. DESs are three-component eutectic mixtures consisting of a certain stoichiometric ratio of hydrogen bond acceptor and hydrogen bond donor, whose freezing point falls dramatically below the melting point of the pure substances of each component. Researchers have classified DESs as a new class of ILs or IL analogs because they share many physical and chemical properties with ILs. The common hydrogen bond acceptors that can form DESs contain quaternary ammonium salt (e.g., choline chloride) and zwitterion (e.g., betaine), whereas thiourea, carboxylic acids (e.g., phenylacetic acid, malic acid, citric acid, and succinic acid), polyols (e.g., ethylene glycol, glycerol, butanediol, and xylitol), amino acids, sugars (e.g., glucose and fructose), and trifluoroacetamide are categorized as common hydrogen bond donors. Low-cost and efficient DESs represented by choline chloride-glycerol were confirmed to sufficiently degrade the PVDF in a cathode electrode. The thermal degradation of PVDF in the DESs was able to separate cathode materials from Al foil. Second, the optimal conditions for cathode material detachment involved a heating temperature of 190 degC, molar ratio of choline chloride to glycerol of 2:1, and heating duration of 10 min, corresponding to a detachment rate of 99.8 wt.%. PVDF has the chemical formula CH2-CF2 n and framework C is tetrahedrally structured. In this context, the F atom of the halogen group located in the second period has a small radius and strong electronegativity, featuring a potent electron-withdrawing ability and linkage capability. Due to the intense electron-withdrawing effect of the F atom, the symmetric H atom is highly susceptible to attack, performing an elimination reaction to form an unsaturated double bond. Under the action of DESs at a high temperature, the unsaturated double bonds in PVDF are oxidized to hydroxyl and carbonyl groups, culminating in the formation of unsaturated ketone in the molecular chain. Potassium carbonate-ethylene glycol DES was also identified for separation of electrode materials. Mechanistic analysis showed that the chain reaction of carbonate ions with PVDF caused polymer degradation, which resulted in the effective separation of cathode material particles and Al foil. The electrode materials can be completely separated under mild reaction conditions (100 degC, 20 min), and the DES can be recovered and reused for multiple cycles. The isolated electrode materials are of high purity and have no change in crystal structure. Compared with systems such as ILs and NMP, DESs stand out in practical application, with the advantages of high security and minimal ecotoxicity, promising to take the lead as new cost-effective solvents with latent industrial application. However, DESs are applied mainly for recovering metals from the retired power LIBs, and relatively little research has been conducted on their use for the degradation of PVDF. 3.4.4 Bio-Based Solvents The global prosperity of the chemical industry is constantly driving the consumption of organic chemical solvents. However, organic solvents are complicated to synthesize, laden with apparent toxicity, and are challenging to access, manage, and dispose of. As a result, there has been an uprising of green bio-based solvents, which are derived from raw biomass and/or produced through biochemical methods. Bio-based solvents are now deemed a new class of environmentally friendly green solvents due to their application advantages, including sustainable regeneration, non-volatility, non-toxicity, biodegradability, and recyclability. With waste oil as a cheap biomass feedstock and methanol as an ingredient, a bio-based short-chain fatty acid methyl ester (FAME) solvent was synthesized. At 190 degC, the cathode material of the retired LPF battery was stripped from the Al foil after heating treatment in FAME solvent for 20 min. In this case, FAME represents a transitional-state solvent capable of dissolving PVDF under heating condition, and the swelling of PVDF in FAME solvent could be attributed to the cross-linking reaction of hydrogen bonds. In general, FAME solvent offers a new option for recovering PVDF from the retired LIBs. Compared with molten salts, ILs, and DESs, bio-based solvents deliver environmental and economic benefits and offer a potentially promising direction for future solvent-based separation and defluorination of PVDF. 3.4.5 Supercritical Fluid Extraction Supercritical fluid extraction is a novel technique of selective extraction and separation by utilizing a supercritical fluid (i.e., a fluid above the critical temperature and pressure) as an extractant, as this has the characteristics of both liquid and gas by controlling the temperature and pressure. In a common extraction medium, CO2 benefits from non-toxicity, high safety, affordability, and low critical pressure and temperature, and can quickly and reliably separate the target products from the mixture. The combination of supercritical carbon dioxide (SC-CO2) and the co-solvent dimethyl sulfoxide could selectively extract PVDF from the cathode electrode of the retired power LIB. In this process, SC-CO2 and dimethyl sulfoxide first achieved mutual solubility, and the flowing SC-CO2 extracted the PVDF molecules dissolved in dimethyl sulfoxide from the pores of the cathode materials. Subsequently, 98.5 wt.% of PVDF was extracted at a temperature of 70 degC, pressure of 80 bar, and duration of 13 min. Fourier Transform Infrared Spectrometer and Thermal Gravimetric Analyzer confirmed that the PVDF surface chemical groups and contents remained intact after extraction, indicating that the recovery of PVDF by SC-CO2--dimethylsulfoxide could be a physical dissolution-extraction process. Considering the high efficiency, relatively low energy consumption, and environmental friendliness of SC-CO2, this approach has the potential to serve as a new technology for recovering PVDF from the retired LIB cathode electrodes. A solvent system is a highly targeted and mild separation process for cathode electrodes, i.e., it will only dissolve, swell, or degrade the PVDF in a targeted manner. Existing solvent systems have not been reported to cause damage to metal oxides in the cathode materials or Al foil. In the battery regeneration route, the deactivated PVDF may affect the performance of newly assembled batteries. Therefore, pre-removal is required. To reduce the intervention of impurities, both thermochemistry and solvent chemistry are effective routes. Physical crushing-sorting is more likely to be adopted by the hydrometallurgical route because it may introduce considerable Al and Cu impurities. Little research has aimed at practical production, the limitations of solution chemistry itself account for this phenomenon: 1) in comparison with the aqueous phase, organic solvents bear certain ecological threats and toxicological properties; 2) high viscosity results in the adhesion of organic solvents on the surface of solid materials, leading to residue problems in practical application; 3) small-molecule compounds after degradation of PVDF, such as hydrocarbons and organic fluorides, are challenging to separate by traditional techniques when dissolved in organic solvents, resulting in disposal difficulty after solvent saturation. Hence, solvent chemical separation is presently stuck in the laboratory stage and fails to proceed to industrial application. 4 Suggestions and Prospects Vehicle electrification has inexorably become a trend, and the mass production of EVs will lead to a wave of retirement of new EVs globally. However, as the core component of EVs, power LIBs, with their short life cycle and complex manufacturing structure, are likely to pose new challenge of resource recovery. Recycling valuable metals such as Li, Ni, Co, and Mn in the retired LIBs can effectively avoid the risk of upstream raw material scarcity and price fluctuation, producing remarkable environmental and economic benefits. Moreover, the assembled materials of the retired LIBs may trigger metal and/or organic pollution in the recycling process and affect the ecological environment as well as human health through the food chain. In contrast to the recovery of metals, the processing of PVDF--an irreplaceable battery component material--has not been investigated in depth, requiring high priority in the future research. Pre-separation of cathode materials and Al foil is a crucial link for the efficiency and quality of metal extraction from cathode materials. The selection of pre-separation technology depends on the recovery route of metals as the cornerstone for design. However, despite the high priority that ought to be given to PVDF considering its environmental risks and potential hazards, there remains a lack of relevant research on controlling organic fluoride contamination. Consequently, research and development enhancing the corresponding technology is essential for designing appropriate recycling strategies. In the current industrial recovery of retired power LIBs, thermochemical defluorination tends to be the most prevalent application, with relatively mature technology. However, industrial challenges remain in practice, such as HF corrosion of pipelines, shortened operating life of equipment, and dioxin formation. As such, the focus of subsequent studies should include the research and development of anti-corrosion materials until a new technological breakthrough is achieved. Moreover, in actual production, the release of fluoride should be strictly controlled through enhanced monitoring, for the purpose of averting secondary environmental contamination arising from dioxin emissions. Organic fluoride displays the highest ecological risk among the components of retired power LIBs. Despite the contribution of PVDF to the historical development and prevalence of LIBs, endeavors ought to be exerted in future research to eliminate latent environmental pollution at the potential sources. Furthermore, battery research and development companies and scientific research institutions should pay more attention to fluorine-free alternatives. So far, with the advancement of scientific research, relevant studies on solid-phase electrolytes have gradually progressed, offering new opportunities for reducing or even abolishing the adoption of organic fluorides. 5 Conclusions The organic binder PVDF in the LIBs binds the electrode materials and current collectors, enhancing the electronic contact among the electrode materials, conductive agents, and current collectors. However, the stable structure of PVDF and the existence of C-F bonds have caused problems in the separation of cathode material and Al foil as well as potential environmental pollution from fluorine-containing compounds during the recycling process for spent LIBs. We critically reviewed the separation technologies of cathode materials and Al foil as well as the corresponding reaction behavior and transformation mechanisms of PVDF, including physical separation, solid-phase thermochemistry, solution chemistry, and solvent chemistry. Current awareness of the environmental risks of PVDF during the recycling and disposal of retired LIBs is inadequate, and the research on organic fluorine pollution is insufficient. Strengthening the recycling technology research and developing multi-technology/inter-disciplinary collaboration should be the focus of future research. In addition, the development of fluorine-free alternatives and solid-state electrolytes can point the way to eliminating fluorine contamination at the source. Conflict of Interest The authors declare no conflict of interest. Acknowledgements The authors appreciate the financial support from the Hong Kong Research Grants Council [PolyU 15222020]. Mengmeng Wang is currently a RGC Postdoctoral Fellow at Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University. Prior to joining PolyU, she received her Ph.D. degree from Tsinghua University in 2021. She was exchanged as a visiting student for one year at Yale University. She got the Postdoctoral Fellowship Scheme from Research Grants Council of Hong Kong. Her research interests mainly focus on critical metals recovery from spent lithium-ion batteries by environmentally friendly technologies. Kang Liu is currently a Research Fellow at Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University. He received his Ph.D. degree from Research Centre for Eco-Environment Science, Chinese Academy of Sciences in 2016. He carried out postdoctoral research in the College of Environment, Tsinghua University in 2018-2021. He also worked as Research Assistant at Asia-Pacific Regional Centre of the Stockholm Convention, Environmental Management Professional Committee of the Chinese Society of Management Sciences, and Circular Economics Branch of the Chinese Environmental Sciences Society. His main research direction is the recycling of retired power batteries. Dan Tsang is a Professor at Department of Civil and Environmental Engineering and Director of Research Centre for Environmental Technology and Management at The Hong Kong Polytechnic University. He also serves as Pao Yue-Kong Chair Professor of State Key Laboratory of Clean Energy Utilization at Zhejiang University. He was a Visiting Professor at University of Queensland, Visiting Scholar at Stanford University and Ghent University, Senior Lecturer at University of Canterbury, and Postdoctoral Fellow at Imperial College London. Dan and his team strive to advance our fundamental knowledge and develop carbon-negative engineering solutions to actualize Carbon Neutrality and Sustainable Development Goals. |
PMC10000286 | 2D nanostructured materials have been applied for water purification in the past decades due to their excellent separation and adsorption performance. However, the functional 2D nanostructured molybdenum trioxide (MoO3)has rarely been reported for the removal of dyes. Here, functionalized MoO3 (F-MoO3) nanosheets are successfully fabricated with a high specific surface area (106 cc g-1) by a one-step mechanochemical exfoliation method as a highly effective adsorbent for removing dyes from water. According to the Raman, X-ray photoelectron spectroscopy, Fourier transform infrared (FTIR), and selected area electron diffraction analysis, functional groups (hdroxyl groups, amide groups, amine groups and amino groups) are identified in the as-prepared F-MoO3 nanosheets. The attached functional groups not only facilitate the dispersal ability of F-MoO3 nanosheets but also enhance the adsorption capacities. Thus, the performance (up to 556 mg g-1 when the initial concentration of Rhodamine B solution is 100 mg L-1) of as-prepared F-MoO3 nanosheets is almost two times higher than other reported MoO3 materials. Furthermore, the FTIR spectra, isotherm, and several factors (e.g., adsorbent dosage and adsorbate dosage) are also systematically investigated to explore the adsorption mechanism. Therefore, this work demonstrates that the F-MoO3 nanosheets are a promising candidate for wastewater treatment. Functional molybdenum trioxide (F-MoO3) nanosheets with a specific surface area of 106 cc g-1 are successfully fabricated by a one-step mechanochemical exfoliation method. The adsorption capacity of the F-MoO3 nanosheets is up to 556 mg g-1 for removing Rhodamine B dye from water, demonstrating great potential in industrial dye removal. adsorption ball milling F-MoO 3 nanosheets water purification Australian Research Council Discovery ProgramDP190103290 Australian Research Council Future FellowshipsFT200100730 FT210100804 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Y. Ma , L. Wang , D. Liu , Y. Liu , G. Yang , Y. Qian , W. Lei , Functionalized MoO3 Nanosheets for High-Efficiency RhB Removal. Global Challenges 2023, 7 , 2200154. 10.1002/gch2.202200154 pmc1 Introduction In the past decades, various kinds of dyes have been widely used in different industries, such as textile, paper, cosmetics, and printing. Most dyes are considered as primary water contaminants due to their toxicity to the environment and human health. Therefore, considerable attention was drawn to the effective removal of dyes from wastewater. To date, various methods, including sorption, filtration, degradation, and flocculation, are used to separate dyes from wastewater. Among these methods, sorption is employed as an efficient way to purify water pollution in terms of flexible design, ease of separation, and low cost. The sorption capacities of adsorbents can be affected by several factors, including solution pH, contact time, reaction temperature, ionic strength, the volume of adsorbents, and the concentration of adsorbate solution. Among them, ionic strength is one of the most important and complicated factors. For the adsorption mechanism, dyes are mainly attracted by electrostatic attractions, hydrophobic interactions, surface functional group interactions, and hydrogen bonding interactions in aqueous solutions. The functional groups are proven to affect ionic strength, surface charge, and hydrophilicity. However, to date, the adsorption efficiency of dyes affected by the functional groups and molecular structure is rarely reported. Therefore, the relationship between functional groups on the surface of adsorbents and their adsorption performance still needs to be further explored. In recent years, many adsorbents including activated carbon, resin, boron nitride, and polymers have been studied for dye removal from wastewater. However, these adsorbents still have a range of limitations, such as low adsorption capacity, poor recyclability, and potential secondary pollution. Therefore, 2D materials are attracting great interest due to their unique physical and chemical features. Molybdenum trioxide (MoO3) is a typical 2D material, which is structurally similar to hexagonal boron nitride and graphene, holding stacked layers together by weak van der Waals forces. Molybdenum oxide is widely applied in many fields including supercapacitors, batteries, catalysts, and sensors, due to its unique structure and properties. Recently, a-MoO3 was proven as a potential effective adsorbent. Nevertheless, few investigations about dye sorption capacities and the mechanism of functional molybdenum oxide nanosheets have been reported up to date. Here, ball milling, as a one-step exfoliation and functional method, was applied for developing nanostructured MoO3 in this work. Meanwhile, functional groups (hydroxyl (OH) group, amide (CONH) group, amine (NH2) group and amino (NH) group) are designed to attach on the surface of MoO3 for boosting the dye sorption ability of the functionalized MoO3 (F-MoO3) nanosheets. The F-MoO3 nanosheets exhibited superb performance in Rhodamine B (RhB) removal from water (Q m = 556 mg g-1), which is much higher than the current reported literature, showing a bright future for wastewater treatments. 2 Results and Discussion 2.1 Synthesis and Characterization of F-MoO3 Nanosheets As Figure 1 illustrates, the F-MoO3 nanosheets were prepared via a one-step method of the functionalization and exfoliation of commercial MoO3 with urea assistance. The usage of urea was not only for facilitating the exfoliation process but also for being a functional group source. Figure 1 Schematic illustration of the preparation of the F-MoO3 nanosheets. The surface morphology and microstructure of as-prepared F-MoO3 nanosheets were analyzed by scanning electron microscopy (SEM) (Zeiss Supra 55 VP) and transmission electron microscopy (TEM) (JEOL 2100) results. The SEM image of F-MoO3 powder obtained by the freeze-drying process and the TEM image of F-MoO3 nanosheets prepared by vaporing the F-MoO3 suspension on a copper mesh were displayed in Figure 2a,b, which indicated that the size of F-MoO3 was significantly decreased after ball milling, compared with the pristine a-MoO3 . The nanostructure of typical F-MoO3 nanosheets was shown in a high-magnification TEM image . A MoO3 nanosheet with a length of 60 nm was densely packed by few-layer nanosheets. The lattice fringes were confirmed in Figure 2d, which exhibited constant d-spacings of 0.37 and 0.39 nm, corresponding to (200) and (002) planes, respectively. The inset of Figure 2d was the selective area electron diffraction (SAED) pattern of F-MoO3 nanosheets, which confirmed the crystal structure of the as-prepared F-MoO3 nanosheets. The lateral size distribution was shown in Figure 2e. There were 150 pieces of MoO3 nanosheets counted in total. Meanwhile, the lateral size of MoO3 nanosheets is distributed from 20 to 200 nm. The thickness profile was further studied by atomic force microscopy (AFM). As shown in Figure 2f, the thickness of the as-prepared F-MoO3 nanosheets was 8-9 nm. Figure 2 Morphology and structure characterizations of F-MoO3 nanosheets. a) SEM image and enlarged SEM (inset) image of F-MoO3 nanosheets. b,c) TEM image. d) HRTEM image, inset is SAED pattern. e) Lateral size distribution histogram of as-prepared F-MoO3 nanosheets. f) AFM image. The crystal structure of F-MoO3 was confirmed by X-ray powder diffraction (XRD) (Panalytical X'Pert PRO diffraction system with a Cu Ka radiation) As shown in Figure 3a, all the diffraction peaks are indexed to the orthorhombic crystal structure of MoO3 (a = 3.9450 A, b = 13.8250 A, c = 3.6940 A). The Raman spectra (Renishaw Raman spectrometer) of MoO3 powder were collected using a 532 nm laser and displayed in Figure 2b, which supported the crystal structure obtained from XRD. As shown in Figure 2b, the diffraction peaks at 665, 817, and 994 cm-1 were the asymmetric stretches and symmetric stretch of the terminal oxygen atom (Mo6+ = O), respectively, relating to the MoO3 orthorhombic crystal phase. Meanwhile, the high intensity with sharp background peaks suggests highly ordered MoO3 nanostructures. Besides, Raman spectroscopy was employed to determine the chemical properties of the F-MoO3 . Several diffraction peaks at 283, 431, 1183, 1648, and 2760 cm-1, were assigned to the bending of terminal oxygen, carbonyl (C=O) group, NH, and CONH, respectively. Figure 3 Spectroscopic characterizations. a) XRD patterns, b) Raman spectra, High-resolution XPS spectra of F-MoO3 on c) full scan, d) O 1s, e) N 1s, f) C 1s, g) Mo 3d, h) FTIR spectrum, and i) Nitrogen adsorption-desorption isotherms of pristine MoO3 and F-MoO3. The chemical component of F-MoO3 nanosheets was confirmed by X-ray photoelectron spectroscopy (XPS) (ESCALab MKII X-ray photoelectron spectrometer) measurements. As shown in Figure 3c, the XPS survey spectrum revealed the existence of molybdenum (Mo), oxygen (O), carbon (C), and nitrogen (N) of which peaks at 231.42, 284.28, 398.28, and 530.1 eV corresponds to Mo 3d, C 1s, N 1s, O 1s signals, respectively. The high-resolution XPS spectra were used to further study the binding energy of surface functional groups . The high-resolution XPS spectrum of O 1s presented two peaks at 531.3 and 530.4 eV, which can be deconvoluted into C=O bonds and Mo--O bonds, respectively. It is necessary to notice that there is a little shift in these peaks compared with current reports due to the oxygen vacancy. Figure 3e displays the N 1s spectrum, which can be deconvoluted into two peaks with binding energy at 398.7 and 399.7 eV, connecting to C--N bindings and N--H bindings, respectively. According to Figure 3f, the XPS spectrum of C 1s can be deconvoluted into three peaks. The peak at 284.8 eV was related to C--H binding, while the peaks at 286.6 and 289.2 eV were attributed to C--N bindings and C=O bindings, respectively. The results were in good agreement with the Raman spectrum, demonstrating the existence of CONH and NH2 groups. Furthermore, the high-resolution Mo 3d spectrum can be distinguished as two major contributor peaks located at 232.9 and 236.1 eV, which were typical characteristic peaks of the 3d doublet of Mo6+. The functional group continued to be studied by the Fourier transform infrared (FTIR) spectrum. (Nicolet 7199 FT-IR) According to Figure 3h, the pristine MoO3 exhibited the characteristic peaks at 995, 867, and 584 cm-1, while the FTIR spectrum of as-prepared F-MoO3 nanosheets showed different peaks. The shoulder extended from 3200 to 3500 cm-1 can be ascribed to --OH stretching vibrations and --NHx(x=1,2) stretching vibrations. The peaks from 1550 to 1700 cm-1 were assigned to stretching vibrations of the attached CONH groups (C=O and linkage of CONH groups). The peaks from 500 to 880 cm-1 related to the Mo--O--Mo stretching vibration, and the range from 950 to 1000 cm-1 were assigned to the characteristic bonds of M=O. Furthermore, Three peak shifts of F-MoO3 can be observed at 945, 1049, and 1153 cm-1, which suggests partly Mo=O bonds broken and attached by functional groups. It is in agreement with the results as indicated in the above SAED, Raman, and XPS data. Therefore, the existence of functional groups, including NHx (x=1,2), CONH, and OH groups, was confirmed. They were attached to the surface of the F-MoO3 nanosheets and facilitated F-MoO3 nanosheets to form a stable homogeneous suspension over 2 weeks. . The specific surface area data of pristine and F-MoO3 was confirmed by Brunauer-Emmett-Teller (BET) (Quantachrome Autosorb iQ-MP/XR), shown in Figure 3i. It suggested that the specific surface area of F-MoO3 was 106 cc g-1 (Barrett-Joyner-Halenda model) or 161.194 cc g-1 (BET model), which was much higher than the pristine MoO3 (5 cc g-1). The results indicated that the pristine MoO3 was thoroughly exfoliated into nanosheets after the high-energy ball milling process. 2.2 The Performance of Dye Removal from Water The ultraviolet-visible spectra (UV-vis)(Cary 300) of the RhB solution before and after adsorption was shown in Figure 4a. The RhB has a characteristic peak at 554 nm, but the intensity of the peak vanished after the adsorption, implying the RhB molecules were removed after adsorption by F-MoO3 nanosheets. The inset showed a significant color disappearance after adsorption, supporting the removal of the RhB molecules from the aqueous solution. The effect of contact time is also an important factor in dye adsorbing process. In Figure 4b, the effect of contact time on the adsorption of F-MoO3 nanosheets was presented. Approximately 70% of RhB molecules were removed within 30 min, suggesting high efficiency for RhB removal. Besides, the effect of adsorbent dosage was another important factor affecting the adsorption capacities. As shown in Figure 4c, the removal quantity of RhB increased with the decrease of absorbate dosage, due to higher absorbent dosage inducing more active binding sites. The adsorption isotherm fitted by the Langmuir model exhibits a maximum adsorption capacity Qm of 556 mg g-1 (RhB concentration is 100 mg L-1), which was significantly higher than the relevant previous reported materials, listed in Table 1 . The results revealed that the F-MoO3 nanosheets can be a promising candidate for RhB removal from an aqueous solution. Figure 4 a) UV-vis absorbance plots for RhB aqueous solution in presence of MoO3 nanosheets over time. The inset showed the RhB solution before (left) and after adsorption (right). b) The removal efficiency of MoO3 nanosheets in 100 mg L-1 RhB solutions. c) The effect of adsorbate dosage on RhB removal. d) Absorption isotherm of RhB on MoO3 nanosheets. Table 1 The maximum RhB adsorption capacity of different adsorbents Adsorbent Qm [mg g-1] Reference MoO2 - nanoparticles 256 MoO3 nanowires 321 MoO3 - hierarchical 204 MoO3 nanorod 326.8 MoO3 nanosheets 556 This work John Wiley & Sons, Ltd. The effect of solution pH and ionic strength on the adsorption of RhB was investigated under acidic condition at room temperature. The initial pH of RhB (100 mg L-1) is 3.7, and then a certain amount of hydrochloric acids (H+) or sodium hydroxides (OH-) was respectively added into the solution for adjusting the pH. As shown in Figure S5 (Supporting Information), a trend was clearly observed that the adsorption capacity increased with increasing the solution pH, corresponding to the protonation degree of functional groups on F-MoO3 nanosheets. Furthermore, the adsorbed RhB on the F-MoO3 nanosheets can be quickly desorbed by dispersing in ethanol. Figure S6 (Supporting Information) showed the recycling ability of RhB onto F-MoO3 nanosheets. The recovery rates of the RhB solution on F-MoO3 nanosheets reached 99.41% after desorption by dispersing in ethanol, even though the adsorption capacity slightly decreased from 477 to 474 mg g-1, indicating an excellent recovery ability. Moreover, tap water (containing various cationic ions) was used to prepare an RhB solution (100 mg L-1) for stimulating the real water. As shown in Figure S7 (Supporting Information), the adsorption capacity of RhB on F-MoO3 nanosheets slightly decreased from 477 to 416 mg g-1 when other cationic ions existed. The results indicate that the competitive adsorption between the other cationic ions existing in tap water and RhB on F-MoO3 nanosheets led to the reduction of the adsorption capacity. Although the adsorption performance decreased in the stimulated real water, the adsorption capacity (416 mg g-1, RhB/F-MoO3 nanosheets) is still much higher than other currently reported MoO3 materials (Table 1), showing great potential in industrial dye removal. 2.3 Adsorption Mechanism To further investigate the adsorption mechanism, the FTIR of F-MoO3 nanosheets before and after dye adsorption were performed to determine the interaction between cationic dyes and MoO3. As literature reported, several functional groups, including the CONH groups and OH groups, can affect the adsorption capacity of cationic dyes, while the NH groups will slightly decrease the adsorption capacity, corresponding to the sorption results obtained from the FTIR spectra . The change in the intensity of characteristic peaks before and after RhB adsorption confirmed that the RhB molecules were attaching to the surface of F-MoO3 nanosheets through the electrostatic interaction and hydrogen bonds. As shown in Figure 5, the peaks of the --NHx(x=1,2) at 3440 and 3352 cm-1, C=O bond at 1645 cm-1, and the linkage of the CONH groups (C--N, N--H) at 1585 cm-1 remained after RhB adsorption, indicating that the RhB molecules were not attached to the --NHx(x=1,2) and --CONH groups. Meanwhile, the peak of --OH stretching vibrations (shoulder from 3257 to 3599 cm-1) vanished after RhB adsorption, demonstrating the functional groups occupied by the RhB molecules. Thus, by introducing new functional groups was not only increasing the adsorption capacities but also facilitatind the dispersal ability of F-MoO3 in the aqueous solution. Moreover, the increasing negative charge in the aqueous solution was also a factor for high adsorption capacities. As shown in Tables S1 and S2 (Supporting Information), both pristine MoO3 and as-prepared F-MoO3 nanosheets exhibited negative potential values, -31.5 +- 0.6 and -45.5 +- 1 mV, respectively. The absolute z-potential of F-MoO3 nanosheets was increased after ball milling, which enhanced the strength of electrostatic interaction. Furthermore, the protonated functional groups enhanced the absolute z-potential of the F-MoO3 nanosheets by increasing the pH of the solution, leading to a higher adsorption capacity of RhB on F-MoO3 nanosheets via electrostatic forces. Meanwhile, the adsorption capacity of RhB on F-MoO3 nanosheets decreased in real water, due to the negatively charged active binding sites being partly occupied by the other cationic ions in tap water. Besides, the anionic dye (reactive black 5) was tested to verify if the RhB dye was adsorbed on F-MoO3 nanosheets via electrostatic attractions. As shown in Figure S8 (Supporting Information), the concentration of the solution barely decreased after the adsorption, demonstrating that the negatively charged F-MoO3 nanosheets can hardly adsorb anionic dyes. Therefore, it is concluded that the electrostatic interaction between RhB and functional groups on F-MoO3 nanosheets mainly contributes to the high adsorption capacity of RhB on F-MoO3 nanosheets. Meanwhile, it was reported that the surface structure and the specific surface area can affect the dye adsorption capacity as well. The increase of surface area on F-MoO3 nanosheets (106 cc g-1) was another reason for the high adsorption capacities. Figure 5 FTIR spectra of F-MoO3 nanosheets before and after RhB adsorption. 3 Conclusion In this study, high-energy ball milling method was successfully applied to produce F-MoO3 nanosheets with the assistance of urea as the milling agent and functional group source by appropriately controlling the process parameters. According to the Raman, FTIR, and XPS analysis, functional groups (--OH, --CONH, --NHx (x = 1, 2)) were recognized by attaching to the surface of MoO3 nanosheets. Then, the as-prepared F-MoO3 nanosheets were utilized to adsorb RhB from aqueous solutions. The obtained F-MoO3 nanosheets as an adsorbent exhibited high adsorption capacity for RhB with 556 mg g-1, compared with other recently reported nanostructured MoO3. Several factors, including electrostatic interaction, surface complexation, and hydrogen bonding can affect the adsorption of RhB on F-MoO3 nanosheets, while the electrostatic contact between surface functional groups and RhB molecules played a main role during the adsorption process. Thus, all features as reported demonstrated that the F-MoO3 is a promising candidate for wastewater treatment. 4 Experimental Section Synthesis Method F-MoO3 nanosheets were prepared by modifying Lei's ball milling method. 10.5 g of commercial a-MoO3 (Sigma, Molybdenum (VI) oxide, 99.5%) and urea (Sigma, ACS Reagent, 99.0-100.5%) mixtures with a 1:20 mass ratio and ten stainless steel balls (diameter = 10 mm) were placed in a stainless steel milling jar. Then, the mixtures were milled for 40 h at a speed of 500 rpm while jars were settled in the ball mill machine (Fritsch P7). After several times centrifuging with ethanol for 30 min at a speed of 12 000 rpm to remove urea, few-layer F-MoO3 nanosheets suspension and bulk MoO3 powder could be separated by centrifuging for 10 min at a speed of 3000 rpm. After freezing by liquid nitrogen for 30 min, the as-prepared suspension was placed in the freeze-dryer (Christ Beta 2-8 LSCbasic) for 48 h to obtain F-MoO3 nanosheets powder. Adsorption Experiment RhB was adopted to evaluate the dye removal abilities of the F-MoO3 nanosheets. Dye solutions (RhB) with different concentrations were prepared by diluting a certain concentration dye solution (100 mg L-1) determined by UV spectra (554 nm for RhB). The calibration curve was fitted from the spectra of the standard solutions (R 2 > 0.99). In a typical F-MoO3 nanosheets absorption experiment, a certain amount of the F-MoO3 nanosheets were added to 10 mL of RhB aqueous solution (100 mg L-1) in the dark condition under magnetic stirring for variation time (5-1200 min). After absorption, the suspension was centrifuged to remove F-MoO3, and the amount of dye left in the supernatant was assessed by a UV spectrometer. The adsorption isotherm was obtained by adjusting the initial dye solution concentration. The removal efficiency (%Removal) and the equilibrium adsorption capacity (Q e, mg g-1) were calculated by the following Equations (1) %Removal=Co-CeCox00% (2) Qe=(Co-Ce)Vm where C o (mg L-1) and C e (mg L-1) are the concentration of before and after absorption, respectively. The m (g) is the weight of the absorbent, and V (L) is the liquid volume. Conflict of Interest The authors declare no conflict of interest. Supporting information Supporting Information Click here for additional data file. Acknowledgements Y.M. and L.W. contributed equally to this work. The authors acknowledge support from the Australian Research Council Discovery Program (DP190103290) and Australian Research Council Future Fellowships (FT200100730, FT210100804). The authors also thank the IFM EM technician group for their support in the characterization of the materials. Y.M. thanks Ms. Yue You for her help on UV-vis analysis. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. |
PMC10000288 | In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well-studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months. CNVs are classified using the American College of Medical Genetics and Genomics guidelines and CNVs in our cohort are compared to an autism spectrum disorder (ASD) cohort, and to a control cohort. Pathogenic CNVs are identified in 5 of 116 cases (4.3%). Variants of uncertain significance (VUS) favoring pathogenic CNVs are identified in 9 cases (7.8%). Several CNVs are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, and schizophrenia. The structural variant 47,XXY is identified in two cases (2/69 boys, 2.9%) not previously diagnosed with Klinefelter syndrome. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls (p = 0.007) and are not significantly different from the ASD cohort. The finding of pathogenic or VUS favoring pathogenic CNVs, or structural variants, in 12.1% of cases, combined with the observation of higher pathogenicity scores for deletions in SUDP versus controls, suggests that CMA should be included in the genetic evaluation of SUDP. Chromosomal microarray (CMA) data for 116 sudden unexplained death in pediatrics (SUDP) cases is compared to an autism spectrum disorder (ASD) cohort and a control cohort. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls (p = 0.007) and are not significantly different from the ASD cohort. This data suggests that CMA should be included when evaluating SUDP. autism spectrum disorder chromosomal microarray death genetics genomics sudden infant death syndrome sudden unexplained death in childhood Robert's Program on Sudden Unexplained Death in PediatricsJude Zayac FoundationNIH/NICHD K23HD102589 R01 HD 090064 R01 HD 020991 Boston Children's Hospital IntellectualDevelopmental Disabilities Research Center Molecular Genetics Core FacilityP50HD105351 NIH Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNIH/NIMH U01 MH119690 source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 C. A. Brownstein , E. Douard , R. L. Haynes , H. Y. Koh , A. Haghighi , C. Keywan , B. Martin , S. Alexandrescu , E. A. Haas , S. O. Vargas , M. H. Wojcik , S. Jacquemont , A. H. Poduri , R. D. Goldstein , I. A. Holm , Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age. Advanced Genetics 2023, 4 , 2200012. 10.1002/ggn2.202200012 pmc1 Introduction Sudden unexpected death in pediatrics (SUDP) includes sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC). The broader term of SUDP encompasses unexpected deaths in apparently healthy children less than 1 year of age (SIDS), or older than 1 year of age (SUDC), that remains unexplained despite a complete autopsy, death scene investigation, and ancillary testing, though most sudden, unexpected pediatric mortality occurs before the age of 6 months. The etiological model of SUDP includes extrinsic (e.g., sleep position, bed-sharing, tobacco exposure) and intrinsic (e.g., male sex, race, prematurity) factors that together contribute to SUDP. Evidence for a genetic basis in SUDP includes studies using exome sequencing (ES) that have identified a potential genetic cause in up to 20% of SIDS cases, including our finding of clinically informative variants in 11% of SIDS and SUDC cases. Variants have been identified in genes related to epilepsy, cardiac channelopathies, and metabolic diseases (see refs. for reviews). Another important genetic mechanism leading to disease is structural variation, including copy number variants (CNVs), which are deletions or duplications usually 1 kb in size or larger. Although CNVs are present in most individuals in the population and frequently not associated with disease, CNVs have been implicated in a number of conditions, including autism spectrum disorder (ASD), developmental disabilities, attention deficit hyperactivity disorder, schizophrenia, Crohn's disease, epilepsy, and multiple congenital anomalies. In the clinical setting, chromosomal microarray (CMA) analysis is included in the initial evaluation of individuals with ASD, developmental disabilities, multiple congenital anomalies, and epilepsy, to identify CNVs with established disease associations. Additionally, CNVs with potential clinical significance have been detected by CMA analysis in 12-15% of stillbirth cases. However, little is known about the role CNVs, and the genes contained within them, may play in SUDP. One study reported CNVs in 3/27 SIDS cases (11%), including two de novo CNVs at chromosome 6p22, one a 1.9 Mb deletion and the other a 240 kb duplication; a third case had an 8q24.3-qter duplication and a 22q13.3-qter deletion due to an unbalanced translocation. It is hypothesized that unexplained stillbirth, SIDS, and SUDC represent a continuum of as yet unexplained death from fetal life through childhood, with some shared genetic associations already reported involving single nucleotide variants in single genes. A recently reported association of CNVs with stillbirth suggests that CNVs may play a role in SIDS and SUDC and another concluded that SUDC genetic architecture may have some overlap with that of neurodevelopmental disorders. To assess the role of CNVs in SIDS and SUDC, we performed CMA analyses in a cohort of SUDP cases and report on the yield and the types of CNVs identified. In addition, we performed a comparison analysis of our cohort versus a control cohort. We also compared our cohort to an independent cohort with ASD, a condition with well-established CNV associations. Such analysis allows us to investigate potential similarity in the genetic architectures of both disorders, and to provide further recommendations about the diagnosis, therapeutic choices, and pediatric follow-up of infants with a CNV. 2 Experimental Section 2.1 Cases Cases were infants and children who died from SUDP, and cases were either obtained from the San Diego Office of the Medical Examiner or referred to Robert's Program on SUDP at Boston Children's Hospital (BCH) by parents, physicians, medical examiners, and researchers. Informed consent was obtained from parents of cases in Robert's Program; cases from the San Diego Office of the Medical Examiner were obtained in accordance with the California Code, Section 27491.41 for research in SIDS. The study was approved by the BCH Institutional Review Board (IRB-P00011014)). A detailed phenotypic analysis of each case was performed from available data, including the circumstances of death (e.g., risk factors such as bed-sharing); coincident acute illness; general medical history, neurological history; growth and development; physical findings; obstetric and birth histories; and family history including sudden death, febrile seizures, epilepsy, neuro-developmental disorders, and cardiac disorders. When available, detailed neuropathological analysis includes review of materials for specific abnormalities found to be associated with SUDP, including abnormalities of the hippocampus. ES had previously been performed on all cases, and the results were available for this study. 2.2 CMA Analysis Genomic DNA was extracted from tissue specimens or blood using standard protocols (Qiagen, Valencia, CA) and MagNA Pure Compact System (Roche Diagnostics, Pleasanton, CA). Dye-swap array-CGH (comparative genomic hybridization) experiments were performed according to experimental procedures described by Agilent Technologies (Santa Clara, CA) using Agilent 4 x 180 K Surescan arrays. Data analysis was performed using Agilent Cytogenomics Software (Agilent Cytogenomics v3.0.6.6). CNV coordinates were based on the National Center for Biotechnology Information (NCBI) Genome Reference Consortium Human Build 37, GRCh37 (hg19). The absence of heterozygosity (AOH) regions was detected using the Agilent loss of heterozygosity (LOH) algorithm. CNVs were classified as pathogenic or likely pathogenic (P/LP) or variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics guidelines. Using the publicly available tool Franklin by Genoox ), CNVs that were VUS favoring pathogenic were additionally identified, meaning that despite uncertainties, some scientific evidence supportive of pathogenicity existed. Variants with reference to case-specific phenotypic data were reviewed in ClinVar ). The chromosomal intervals were also confirmed in the UK Biobank, Human Gene Mutation Database, Databases of Genomic Variants (DGV), and the Genome Aggregation Database (gnomAD) to confirm rarity and avoid misclassifications. Genes within CNV intervals were assessed for pLi (probability of loss-of-function intolerance). All of the cases had previously undergone ES and the ES data were analyzed for the possibility of a loss of function (LOF) variant on the other allele by querying the ES data for rare variants in genes within the CNV interval using Codified Genomics and WuXi Nextcode browsers. Loss of heterozygosity (LOH) intervals was reported if over 10 Mb in size. 2.3 Controls and ASD Populations Three pooled unselected community-based cohorts were included as controls: IMAGEN (N = 1,802), Generation Scotland (GS) (N = 14,160), and the Lothian Birth Cohort (LBC) (N = 554) . Children with ASD from two pooled cohorts were also included: the Simons simplex collection (SSC) (N = 2,585) and the MSSNG database. Figure 1 Methodological pipeline for the CNV filtering and annotation. The two tables describe the samples of SUDP, ASD, and UP populations before and after filtering. The Venn diagram represents the distribution of the SUDP CNVs discarded in the function of the filtering criteria to which they belong: The size is less than 50 Kb and it is positioned on a sex chromosome. The last density plot represents the distribution of LOEUF score across 19 197 coding genes. A LOEUF score <=0.35 is the defined clinical threshold for intolerant genes. For CNV annotation, the coding gene totally encompassed in deletions and duplications were identified and the LOEUF score of each gene was attributed. For each individual, the number of genes encompassed and the 1/LOEUF scores for deletions and duplications (referred to as the "pathogenicity score") were summed separately. CNV: copy number variant; N: number; NP: neuropsychiatric; DEL: deletions; DUP: duplications; SUDP: Sudden Unexplained Death in Pediatrics; BCH: Boston children hospital; ASD: autism spectrum disorders; SSC: Simons Simplex Collection; UP: unselected populations; G-Scot: Generation Scotland; LBC: Lothian birth cohort; LOEUF: loss-of-function observed/expected upper bound fraction. 1Huguet et al., Mol. Psy. (2021); 2Trost et al., Am. J. Hum. Genet. (2018). A previously published pipeline was used for the detection and filtering of the CNVs from these additional cohorts. To harmonize the SUDP, control, and ASD samples, all CNVs <50 Kb were discarded and individuals with a CNV >=10 Mb were removed . Studies for each cohort were reviewed by local IRBs. 2.3.1 Genome-Wide CNV Pathogenicity Analyses For each individual, a pathogenicity score for deletions and duplications was computed separately using a previously published annotation pipeline . For the pathogenicity score, the loss-of-function observed/expected upper bound fraction (LOEUF) score was used, which was a measure of haploinsufficiency available for 19,197 genes. It was defined as the estimated upper limits of the confidence interval for the observed to expected loss-of-function variants ratio. Each coding gene with all isoforms fully encompassed in filtered CNVs was identified using ENSEMBL map (Gencode V19 (hg19)) and was annotated using the inverted LOEUF (1/LOEUF) score (gnomAD, which ranges from 0.5 (gene tolerant to haploinsufficiency) to 33.3 (gene intolerant to haploinsufficiency). A score of 0 was assigned to individuals with no coding genes encompassed in any CNV. The genome-wide CNV burden was tested with a logistic regression model as follows: (1) ln(odds(Yi=diagnosisi))b0+b1PathogenicityScoreDELi+b2PathogenicityScoreDUPi+b3sexi where PathogenicityScoreDEL/DUP are the sum of 1/LOEUF for deletions (DEL) and duplications (DUP) respectively. b 0, b 1, b 2, and b 3 are the vectors of coefficients for fixed effects. 2.3.2 Neuropsychiatric Loci Analyses Recurrent CNVs are defined as genomic loci flanked by low copy repeat sequences that greatly increase the risk of homologous recombination. These non-allelic homologous recombinations result in similar or identical CNVs in unrelated individuals. Prior studies have identified 47 recurrent CNVs and genes associated with neurodevelopmental or neuropsychiatric disorders (see Table S1, Supporting Information). These regions were annotated in the SUDP, control, and ASD samples if an identified deletion or duplication overlapped at >=40% with a neuropsychiatric CNVs or if a gene associated with neuropsychiatric disorders was disrupted. To test for differences in the prevalence of variants in neuropsychiatric loci between cohorts, two-sided Fisher's exact tests were employed. P-values were adjusted for multiple comparisons using Benjamini-Hochberg correction for false discovery rate (FDR). To address the possibility that bed-sharing resulted in accidental suffocation of a subset of the cohort, the above analyses were repeated removing the bed-sharing cases. 3 Results 3.1 Study Cohort We conducted CMA analysis for 116 SUDP cases. The demographics of the cohort are summarized in Table 1 . Average age at death was 5.7 months (SD 5.8 months) and ranged from 1.5 to 28 months; 69/116 (59%) of cases were boys. Average gestational age was 38.3 weeks. 34/116 (30%) of cases were co-sleeping at the time of death, and 38/116 (43%) of cases were found in the prone position. Three cases had a history of febrile seizures. Tables 2 and 3 summarize the demographics and circumstances around death, respectively, for the cases in which P/LP or VUS favoring pathogenic results were found. Table 1 Demographics of 116 cases of SUDP cohort Total SUDP cohort with CMA data (n = 116) Number of probands with available information Proportion Age at death 116 <2 months 17 15% 2-<6 months 67 58% 6-<12 months 22 19% >=12 months 10 9% Sex 116 Male 69 59% Female 47 41% Ancestry via PCA 116 European 61 53% African American 9 8% East Asian 10 9% Mixed race 36 31% Gestational age 108 >=37 weeks 87 81% 34-37 weeks 12 10% <34 weeks 9 8% Position found (for children <1 year old, who died during sleep) 88 Prone 38 43% Supine 33 38% Side 13 15% Upright/partially upright 4 5% Sleep site 99 Crib 41 41% Adult bed 37 37% Couch 8 8% Car seat 2 2% Held 3 3% Other 8 8% Sleeping circumstances 112 Shared sleep surface 34 30% Sleeping alone 78 70% Personal history Antecedent fever 8 Antecedent minor illness 29 Febrile seizures 3 Other seizures 1 Low birth weight (<2500 g) 17 ROSC 8 Family history SIDS or SUDC 10 SCD <50 years old 3 Febrile seizures 11 Seizures 8 Syncope (excluding vasovagal) 3 John Wiley & Sons, Ltd. Table 2 Demographics of the 18 SUDP cases with pathogenic (5 cases) or VUS favoring pathogenic (13 cases) CMA results Case Sex Ancestry Age at death (in months) Low birth weight [g] 1 F European 3 N:2948 2 F European 5 U 3 F European 3 N 4 M Mixed 3.5 N 5 M Mixed 1.4 Y:2300 6 M Mixed 11 U 7 M Mixed 1.25 U 8 M East Asian 11 N/A 9 M Mixed 4 N 10 F European 2 N 11 F European 6 Y:1814 12 F European 23 U 13 F African American 3.5 N:3255 14 M Asian 5 N 15 M Mixed 1.5 Y:2300 16 M European 3 Y:2293 17 F European 2 N/A John Wiley & Sons, Ltd. Table 3 Circumstances around death for the 18 SUDP cases with pathogenic (5 cases) and VUS Favoring pathogenic (13 cases) CMA results Case Position found Sleep site Sleep circumstances Fever Minor illness 1 Prone Pack n play Alone N Y 2 Supine Adult bed Alone U U 3 Prone Crib Alone N N 4 Prone Crib Alone N N 5 Supine Adult bed Cosleeping N N 6 U U U U U 7 Supine Adult bed Alone U U 8 Supine Sofa Cosleeping Y Y 9 Supine Couch Cosleeping N N 10 Supine Crib Alone N Y 11 Supine Adult bed U N N 12 U Crib Alone N N 13 Supine Other Cosleeping N N 14 N/A awake Awake in crib Alone N Y 15 Supine Adult bed Cosleeping N Y 16 Prone Adult bed Alone N N 17 Prone Adult bed Alone N N U = unknown John Wiley & Sons, Ltd. 3.2 CNVs Detected 3.2.1 Pathogenic CNVs Five of the 116 SUDP cases (4.3%) had CNVs categorized as P/LP and associated with a known disease, though none of these diseases have previously been associated with SUDP. In addition, none of the associated diseases were known to be present in the children harboring the CNVs prior to their death (Table 4 ). Table 4 CNVs scored as pathogenic by Genoox Case no. CNV location CNV coordinates Size [Mb] Type Gene involved Disease associated Notes Evidence Carrier frequency (approximate, gnomAD) 1 chr2p16.3 chr2: 50802121-50909824 0.107 (107.7 kb) Het deletion NRXN1 Autism and seizures, Pitt-Hopkins-like syndrome 2, chromosome 2p16.3 deletion syndrome 11 Mb LOH on chromosome 8 (chr8p11.21-q11.21, encompassing ZMAT5, SFRP1, and MIR54A0) Overlap with established Hi genes or genomic regions 2E (+0.90) Both breakpoints are within the coding region of same gene (gene-level sequence variant) 4.60e-5 2 chr4q31.22 chr4: 147605042-147953051 348 kb Hom deletion TTC29 Spermatogenic failure and Non-syndromic male infertility due to sperm motility disorder Overlap with established Hi genes or genomic regions 2A (+1.00) Complete overlap of an established HI gene/genomic region 4.60e-5 3 chr5q13.2 chr5:68849594-70636824 1.79 Mb Het deletion Several, see Table S2, Supporting Information Spinal muscular atrophy, pseudo-TORCH syndrome Carrier; heterozygous deletion. Phenotype producing in compound heterozygous or homozygous state. Overlap with established Hi genes or genomic regions 2A (+1.00) Complete overlap of an established HI gene/genomic region 2.19e-1 4 chrXp22.33 chrX: 219609-1019952 800 kb Het deletion PLCXD1, GTPBP6, LINC00685, PPP2R3B, and SHOX Short stature, wide phenotypic spectrum, Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia, SHOX-related short stature Overlap with established Hi genes or genomic regions 2A (+1.00) Complete overlap of an established HI gene/genomic region 9.70e-5 5 chr15q15.3 chr15:43851548-43949572 98 kb Het deletion PPIP5K1, CKMT1B, STRC, CATSPER2, PPIP5K1P1-CATSPER2 Deafness-infertility syndrome and autosomal recessive nonsyndromic deafness Carrier; heterozygous deletion. Phenotype producing in compound heterozygous or homozygous state. Overlap with established Hi genes or genomic regions 2A (+1.00) Complete overlap of an established HI gene/genomic region 1.07e-2 John Wiley & Sons, Ltd. Case 1 was a previously healthy 3-month-old girl who died during sleep and was found in the prone position; she had no history of seizures. Neuropathological analysis revealed findings in the dentate gyrus reported to be present in SUDP as well as temporal lobe epilepsy. She had a heterozygous deletion at 2p16.3 (chr2: 50802121-50909824, 107.7 kb) encompassing the gene NRXN1. Deletions at 2p16.3 have variable expressivity and incomplete penetrance and have been associated with susceptibility to developmental delay, ASD, schizophrenia, and dysmorphic features. We previously reported a case with epilepsy and impaired respiratory drive leading to death and single nucleotide variants in both NRXN1 and NRXN2 categorized as VUS. None of the characteristic facial dysmorphisms of NRXN1 deletion were noted in case 1, though they may not be well-developed in a 3-month-old. In addition to the 2p16.3 deletion, case 1 also had an 11 Mb region of LOH at 8p11.21-q11.21 (chr8:40438757-51547523) encompassing ZMAT5, and SFRP1, neither of which are known to be associated with any disease. Previous ES data showed no rare variants in the genes in this LOH region in this case. Case 2 was a previously healthy 5-month-old girl found in the supine position. She had a homozygous deletion at 4q31.22 (chr4:147605042-147953051, 348 kb), which included TTC29. Homozygous and compound heterozygous P/LP variants in TTC29 are associated with spermatogenic failure and non-syndromic male infertility due to a sperm motility disorder, a phenotype unrelated to SUDP and not relevant in females. Case 3 was a previously healthy 3-month-old girl found in the prone position. She had a heterozygous deletion at chr5q13.2 (chr5:68849594-70636824, 1.79 Mb) encompassing several genes including SMN2 and OCLN (see Table S1, Supporting Information). Homozygous or compound heterozygous deletions of this interval are associated with spinal muscular atrophy (SMA) and P/LP variants are associated with pseudo-TORCH syndrome. There is no known phenotype associated with heterozygous deletions of this region. Case 4 was a previously healthy 3.5-month-old boy found in the prone position. He had a deletion at chrXp22.33 (chrX:219609-1019952, 800 kb) encompassing PLCXD1, GTPBP6, LINC00685, PPP2R3B, and SHOX. The only disease gene is SHOX, and SHOX haploinsufficiency leads to a wide phenotypic spectrum that includes syndromic and non-syndromic short stature, a phenotype unrelated to SUDP. Of note, at autopsy, the infant was noted to be below the second percentile for length and below the fifth percentile for weight. Case 5 was a previously healthy 6-week-old boy who was found in the supine position while co-sleeping in an adult bed. He had a heterozygous deletion at chr15q15.3 (chr15:43851548-43949572, 98 kb) encompassing PPIP5K1, CKMT1B, STRC, CATSPER2, and PPIP5K1P1-CATSPER2. Homozygous deletion of STRC and CATSPER2 are associated with autosomal recessive deafness-infertility syndrome DFNB16. Review of the ES data did not reveal P/LP variants in any of these genes in this case. There is no known phenotype associated with heterozygous carriers. 3.2.2 CNVs Categorized as VUS Favoring Pathogenic Nine cases (7.8%) had one or more CNVs categorized as a VUS favoring pathogenic (see Table 5 ). Table 5 CNVs scored as VUS favoring pathogenic by Genoox Case No. CNV Location CNV Coordinates Size (Mb) Type Gene involved Disease associated Notes/ Presumed causative finding on ES Evidence Carrier frequency (approximate, gnomAD) 6 chr15q11.2 chr15:22835886-23080961 0.245 (245 kb) Het deletion TUBGCP5, CYFIP1, NIPA2, NIPA1 15q11.2 deletion syndrome Overlap with established Hi genes or genomic regions 2A (+0.75) 1.89e-3 7 chr15q11.2 chr15:22835886-23082821 0.247 (247 kb) Het deletion TUBGCP5, CYFIP1, NIPA2, NIPA1 15q11.2 deletion syndrome Overlap with established Hi genes or genomic regions 2A (+0.75) 1.80e-3 8 chr13q34 chr13:111181035-111321385 0.140 (140 kb) Het duplication RAB20, NAXD, and CARS2 Developmental delay Also has pathogenic PDHA1 c.1246C>T, p.Arg416Cys Breakpoint(s) within established HI genes 2K (+0.30) 4.60e-5 19 chr2p21 chr2: 45168836-45171619 0.028 (2.78 kb) Het duplication SIX3-AS1, SIX3 No disease association Breakpoint(s) within established HI genes 2K (+0.30) 4.60e-5 chr22q11.21 chr22: 19744894-19758306 0.134 (13.4 kb) Het duplication TBX1 No disease association Breakpoint(s) within established HI genes 2K (+0.30) 0 10 chr2p23.1 chr2: 30102783-30276858 0.174 (174 kb) Het duplication ALK No disease association Breakpoint(s) within established HI genes 2K (+0.30) 1.38e-4 11 chr7q36 chr7: 158424788-158651068 0.226 (226 kb) Het duplication NCAPG2, ESYT2, WDR60 No disease association Breakpoint(s) within established HI genes 2K (+0.30) 4.60e-5 12 chr8p23.2 chr8: 3379054-3602403 0.223 (223 kb) Het deletion CSMD1 Epilepsy and seizures Both breakpoints are within the coding region of same gene (gene-level sequence variant) 2E (+0.45) 1.38e-4 13 chr13q32.3 chr13: 100635361-100752793 0.117 (117 kb) Het duplication ZIC2, LINC00554, LOC105370333, PCCA No disease association Breakpoint(s) within established HI genes 2K (+0.30) 9.50e-5 14 chr22q13.33 chr22: 51063762-51066512 0.275 (2.75 kb) Het duplication ARSA Metachromatic leukodystrophy due to Arylsulfatase A enzyme deficiency Breakpoint(s) within established HI genes 2K (+0.30) 1.84e-4 John Wiley & Sons, Ltd. Cases 6 (an 11-month-old boy) and 7 (a 5-month-old boy) both had a 15q11.2 deletion (chr15:22835886-23080961, 245 kb, and chr15:22835886-23082821, 246 kb, respectively) encompassing TUBGCP5, CYFIP1, NIPA2, and NIPA1 and associated with 15q11.2 deletion syndrome (Burnside-Butler syndrome), a neurodevelopmental disorder characterized by changes in brain morphology, behavior, and cognition). Deletions and duplications of this region are associated with a variety of neurodevelopmental features, including developmental delay, ASD, behavioral problems, and seizures. The 15q11.2 region is also a schizophrenia susceptibility region. Case 7 had evidence for bilamination of the hippocampus on autopsy. Both cases 6 and 7 were specifically noted to be not dysmorphic on autopsy. The developmental histories of the two cases are unknown. Case 8, an 11-month-old boy found in the supine position while co-sleeping on a sofa, had a duplication at chr13q34 (chr13:111181035-111321385, 140 kb) encompassing RAB20, NAXD, and CARS2. A similar duplication in this interval was reported in ClinVar in a patient with a phenotype categorized as "developmental delay and/or other significant developmental or morphological phenotypes" was scored as a VUS; there are no additional publications that confirm this association. On ES we previously found a known pathogenic PDHA1 (chrXp22.12) c.1246C>T, p.Arg416Cys variant responsible for X-linked Pyruvate Dehydrogenase E1-alpha deficiency that had been previously published with functional data. The family history of case 8 is unknown. Case 9, a 4-month-old boy found supine on a couch co-sleeping, had two VUS favoring pathogenic CNVs. The first was a chr2p21 duplication (chr2:45168836-45171619, 2.8 kb) encompassing SIX3 and SIX3-AS1. Heterozygous pathogenic variants in SIX3 are associate with holoprosencephaly. The second CNV was a duplication at chr22q11.21 (chr22:19744894-19758306, 13.4 kb) and encompassing TBX1, which is considered to be responsible for features velocardiofacial syndrome in the presence of haploinsufficiency. Duplication of chr2p21 or chr22q11.21 is not known to be associated with a phenotype. Case 10 was a 2-month-old girl found supine in a crib and had a chr2p23.1 duplication (chr2:30102783-30276858, 174 kb) encompassing ALK. ALK is a receptor tyrosine kinase linked to neuroblastoma and lung cancer susceptibility. Case 11, a 6-month-old girl found supine on an adult bed and noted on past medical history to have a low birth weight but found to be at the 50-75th percentile at autopsy, had a chr7q36.3 duplication (chr7: 158424788-158651068, 226 kb) encompassing NCAPG2, ESYT2, and WDR60. Duplications at chr7q36.3are not known to be associated with any condition. Case 12, a 23-month-old girl, had a personal and family history of febrile seizures. End-folium sclerosis of the hippocampus, a morphological abnormality reported in association with temporal lobe epilepsy, was noted on autopsy. She had a chr8p23.2 deletion (chr8: 3379054-3602403, 223 kb) encompassing CSMD1. She also had a splice region variant previously detected by ES on the other CSMD1 allele (chr8:3611570G>C, NM_033225.5:c.819-6C>G), which is common and found in 6.3% of Ashkenazi in gnomAD. There is a case report of a t(4;8)(p15.2;p23.2) translocation interrupting the coding sequence of CSMD1 segregating with juvenile myoclonic epilepsy, self-limited photosensitive occipital epilepsy, and migraine with aura in a family. An 8p23-p21 deletion encompassing CSMD1 was found in a Saudi Arabian family with autosomal dominant epilepsy and intellectual disability. 3.2.3 CNVs Detected over 1 Mb in Size and LOH In total, a CNV was detected in 90 cases (78% of total cohort). Twenty-one cases (18% of total cohort, 23% of those with a CNV) had a CNV greater than 1 Mb in size (Table S2, Supporting Information). Eleven cases had a CNV deletion 1 Mb or greater (10.3%), and 12 cases had a CNV duplication 1 Mb or greater. One case had two deletions over 1 Mb in size (case 00-0608), and two cases had both a deletion and a duplication larger than 1 Mb (cases 00-0774 and 00-0288). Three cases, 15, 16, and 17 (5-month-old boy, 1.5-month-old boy, and 3-month-old girl) had abnormal CMA results involving the X chromosome (see Table 6 ). The two boy cases (15 and 16) had complete duplication of the X chromosome consistent with a 47,XXY karyotype and the diagnosis of Klinefelter syndrome. Neither case carried an antemortem diagnosis of Klinefelter syndrome, and neither had a history of seizures. Case 15 also had an 81 kb duplication at 15q26.2 encompassing NR2F2 scored as a VUS (see below). CNV findings consistent with a 47,XXY karyotype were found in 2/69 boys in the cohort, which is greater than the general population prevalence of Klinefelter syndrome of 1/500 males (p = 0.04). Table 6 Structural variation and LOH on the X and Y chromosomes Case no. CNV location CNV coordinates (hg19) Size [Mb] Interpretation Frequency in population Notes/presumed causative finding on ES 15 chrXp22.33 chrX:60701-2646815 2.6 Mb chrX duplication, suggesting XXY 2.00e-3 Also has a chr15q26.2 deletion scored as VUS chrXp22.-3 - p11.1 chrX:2676115-58543823 55.8 Mb chrXq11-1 - q28 chrX:61781601-155197079 93 Mb 16 chrXp22.-3 - p11.1 chrX: 2700316-58484662 56 Mb chrX duplication, suggesting XXY 2.00e-3 chrXq11-1 - q28 chrX:61931689-155197079 93 Mb 17 chrXp11.3-q12, LOH chrX:44216570-66956221 22.7 Mb Large LOH, suggesting UPD 2.11e-5 Also has LP variant in SCN1A c.3886T>A, chr2-166866312-A-T, p.S1296T and chr11p15.5 duplication scored VUS encompassing HOTS, and H19. John Wiley & Sons, Ltd. The girl case (17) had a 22.7 Mb area of LOH on chromosome Xp11.3-q12 (chrX: 44216570-66956221) suggesting partial uniparental disomy (UPD). A population-based study of X and Y chromosome variations estimated that UPD of the X chromosome has a population prevalence of 1 in 47,305 women. On ES we previously found this case to have an LP variant in SCN1A (c.3886T>A, chr2-166866312-A-T, p.S1296T) that may explain SUDP. Pathogenic SCN1A variants have been associated with SIDS and sudden unexpected death in epilepsy (SUDEP). 3.2.4 VUS CNVs One or more CNVs categorized as VUS were detected in 53 cases (46%) (see Table 7 for selected VUS [those with a diagnostic exome finding, a CNV seen in more than one case, or a VUS over 1 Mb]). Five of these cases also had an ES finding that potentially explained their death. None of the genes involved were related to a disease that could be associated with SUDP. Table 7 Selected CNVs scored as VUS Case Location Coordinates (hg19) Size Zygosity Genes involved Gene-disease association (if any) Presumed causative finding on ES Carrier frequency (approximate, gnomAD) 18 chr22q11.-3 - q12.1 chr22:25672585-25903543 0.231 (231 kb) Het deletion IGLL3P, LRP5L, CRYBB2P1, MIR6817 Bronchopulmonary dysplasia 1.03e-2 19 chr22q11.-3 - q12.1 chr22:25672585-25903543 0.231 (231 kb) Het deletion IGLL3P, LRP5L, CRYBB2P1, MIR6817 Bronchopulmonary dysplasia 1.03e-2 20 chr22q11.23-q12.1 chr22:25645676-25903543 0.238 (238 kb) Het deletion IGLL3P, LRP5L, CRYBB2P1, MIR6817 Bronchopulmonary dysplasia 1.03e-2 21 chr22q11.-3 - q12.1 chr22:25672585-25903543 0.231 (231 kb) Het duplication IGLL3P, LRP5L, CRYBB2P1, MIR6817 Bronchopulmonary dysplasia Also has MYBPC3 (chr11p11.2) c.3791G>A p.C1264Y 1.30e-2 22 chr9q12 -q21.11 chr9:65632517-71016040 5.38 Mb Het duplication Several (see Table S2, Supporting Information) 0 15 chr15q26.2 chr15:96869390-96950543 0.081 (81 kb) Het deletion NR2F2 (Involved in the hippocampus) Also has a chrX duplication, indicative of XXY 4.60e-5 23 chr15q26.2 chr15:96869390-96896882 0.027 (27 kb) Het deletion NR2F2 (Involved in the hippocampus) 4.60e-5 24 chr11p13 chr11: 31172410-31279781 0.107 (107 kb) Het deletion DCDC1 Also has SCN4A:c.2045C>G, p.Ser682Trp, 2045/5511 9.70e-5 25 chr13q12.12 chr13: 25165136-25327563 0.162 (162 kb) Het duplication TPTE2P6, ATP12A MYBPC3 VUS-FP c.3791G>A, p.Cys1264Tyr 1.38e-4 26 chr14q11.2 chr14: 19794577-20421677 0.627 (627 kb) Het duplication LINC01296, DUXAP10, BMS1P22, BMS1P18, BMS1P17, POTEM, LOC100508046, OR11H2, OR4Q3, OR4M1, OR4N2, OR4K3, OR4K2, OR4K5, OR4K1 TCF4 VUS-FP c.868T>A, p.Ser290Thr 0 27 chr15q15.3 chr15:43851548-43951301 0.997 (997 kb) Het duplication PPIP5K1, CKMT1B, STRC, CATSPER2, PPIP5K1P1-CATSPER2 SCN1A LP c.2045G>T, p.Gly682Val 6.48e-3 John Wiley & Sons, Ltd. Two of the 53 cases with VUS, cases 15 and 23, had overlapping and uncharacterized VUS CNV duplications at 15q26.2 encompassing NR2F2 (chr15: 96869390-96950543, 81 kb and chr15: 96869390-96896882, 27 kb). NR2F2 is linked to hippocampal function, and with a pLi of 0.99, this gene is expressed in most tissues, including in the brain predominately in the hippocampus and amygdala. Although pathogenic variants in NR2F2 are associated with congenital diaphragmatic hernia (CDH), multiple types of congenital heart defects, and with 46,XX sex reversal, duplication of NR2F2 is not known to be associated with a phenotype. Of note, case 15 (81 kb duplication) also had a complete duplication of the X chromosome noted above. Four cases had CNVs at chr22q11.23-q12.1 (chr22:25672585-25903543) involving IGLL3P, LRP5L, CRYBB2P1, and MIR6817 (three deletions and one duplication). This 22q11.23-q12.1 region is associated with bronchopulmonary dysplasia (BPD) in premature infants and in our cases is not likely to be related to SUDP, as our cases were not born prematurely. Two cases had duplications at 15q26.2 (chr15:96869390-96950543 and chr15:96869390-96896882) encompassing NR2F2. Loss of function and missense variants of NR2F2 are associated with disease (46XX sex reversal, CDH, and cardiac defects ). However, there are no known disease associations with duplications of NR2F2. 3.2.5 Genome-Wide CNV Pathogenicity Analyses The computed pathogenicity score was higher in the SUDP cohort compared to the control cohort for deletions (OR 1.24, 95%CI 1.11-1.31, p = 0.007) (Table 8 ). When comparing the SUDP cohort deletion score to that of the ASD cohort, there was no significant difference. Removing bed sharing cases from the analysis did not alter the OR (OR 1.24, 95% CI 1.16-1.33 p = 0.03). The pathogenicity score was not significantly different between the SUDP cohort and controls or ASD cohort for duplications. Table 8 Comparison of sum of 1/LOEUF pathogenicity score, SUDP vs. control, and ASD cohorts SUDP (N = 114) vs. controls Removing bed sharing SUDP (N = 66) vs. controls SUDP (N = 114) vs. ASD Removing bed sharing or unknown if bed sharing SUDP (N = 66) vs. ASD Variable OR [95%CI] p-value OR [95%CI] p-value OR [95%CI] p-value OR [95%CI] p-value DEL DUP DEL DUP DEL DUP DEL DUP Pathogenicity score 1.24 [1.11-1.31] p = 0.007 n.s. 1.24 [1.16-1.33] p = 0.03 n.s. n.s. n.s. n.s. n.s. The pathogenicity score represents the sum of 1/LOEUF of all genes encompassed in CNVs identified in each individual. As sensitivity analysis, we removed cases found while bed-sharing or if this information was not available. SUDP: Sudden Unexplained Death in Pediatrics; ASD: autism spectrum disorder; N: number; OR: odds ratio; 95%CI: 95% of confidence interval; DEL: deletions; DUP: duplications. John Wiley & Sons, Ltd. 3.2.6 Recurrent CNV Analyses In our cohort, 3/114 SUDP cases (2.6%) harbored a deletion involving an interval associated with schizophrenia and/or other neurodevelopmental phenotypes . Cases 6 and 7 both had chr15q11.2 deletions that are associated with schizophrenia, attention deficit hyperactivity disorder (ADHD), and ASD. Case 1 had a NRXN1 deletion, which likewise is associated with a wide spectrum of developmental and neuropsychiatric disorders, including intellectual disability, speech delay, ASD, hypotonia, and schizophrenia. We were interested in whether this rate of CNVs was higher than in ASD or control populations. However, we found no difference in the frequency of known neuropsychiatric CNVs in controls or ASD versus our SUDP cohort after FDR correction (Tables 9 and 10 ). Table 9 Comparison of known neuropsychiatric regions in SUDP and control cohorts Neuropsychiatric associated regions SUDP (N = 114) vs. controls OR [95%CI] p-value Removing bed sharing or unknown if bed-sharing SUDP (N = 66) vs. controls OR [95%CI] p-value 15q11.2 deletion N = 2 vs. 69 4 [0.5-16] p = 0.08 (p-FDR = 0.22) N = 2 vs. 69 7 [0.9-29] p = 0.03 (p-FDR = 0.09) Deleted NRXN1 N = 1 vs. 16 9 [0.2-60] p = 0.11 (p-FDR = 0.22) N = 1 vs. 16 16 [0.4-105] p = 0.07 (p-FDR = 0.12) All deleted and duplicated regions N = 3 vs. 302 1.4 [0.3-4] p = 0.47 (p-FDR = 0.47) N = 3 vs. 302 2 [0.5-8] p = 0.12 (p-FDR = 0.12) All deleted regions N = 3 vs. 158 3 [0.5-8] p = 0.10 (p-FDR = 0.22) N = 3 vs. 158 5 p = 0.03 (p-FDR = 0.09) Deleted recurrent CNVs only N = 2 vs. 130 2 [0.3-8] p = 0.23 (p-FDR = 0.28) N = 2 vs. 130 4 [0.5-15] p = 0.10 (p-FDR = 0.12) Deleted single genes only N = 1 vs. 28 5 [0.1-32] p = 0.18 (p-FDR = 0.27) N = 1 vs. 28 9 [0.2-56] p = 0.11 (p-FDR = 0.12) Legend: None of these results remain significant after FDR correction. The recurrent CNVs category represents the neuropsychiatric regions occurring by non-allelic homologous recombination identified in our cohorts. The single genes category represents the neuropsychiatric genes disrupted by a CNV identified in our cohorts. As sensitivity analysis, we removed cases found while bed-sharing or if this information was not available. SUDP: Sudden Unexplained Death in Pediatrics; N: number; OR: odds ratio; 95%CI: 95% of confidence interval. John Wiley & Sons, Ltd. Table 10 Comparison of known neuropsychiatric regions in SUDP and ASD cohorts Neuropsychiatric associated regions SUDP (N = 114) vs. ASD OR [95%CI] p-value Removing bed sharing SUDP (N = 66) vs. ASD OR [95%CI] p-value 15q11.2 deletion N = 2 vs. 16 6 [0.7-27] p = 0.05 (p-FDR = 0.30) N = 2 vs. 16 10 [1.2-47] p = 0.02 (p-FDR = 0.12) Deleted NRXN1 N = 1 vs. 19 3 [0.1-16] p = 0.33 (p-FDR = 0.69) N = 1 vs. 19 4 [0.1-29] p = 0.21 (p-FDR = 0.38) All deleted and duplicated regions N = 3 vs. 227 0.6 [0.1-2] p = 0.63 (p-FDR = 0.69) N = 3 vs. 227 1 [0.2-3] p = 0.75 (p-FDR = 0.75) All deleted regions N = 3 vs. 113 1.3 [0.2-4] p = 0.5 (p-FDR = 0.69) N = 3 vs. 113 2 [0.4-7] p = 0.16 (p-FDR = 0.38) Deleted recurrent CNVs only N = 2 vs. 83 1.2 [0.1-4] p = 0.69 (p-FDR = 0.69) N = 2 vs. 83 2 [0.2-8] p = 0.26 (p-FDR = 0.38) Deleted single genes only N = 1 vs. 31 1.6 [0.04-10] p = 0.48 (p-FDR = 0.69) N = 1 vs. 31 3 [0.1-17] p = 0.32 (p-FDR = 0.38) Legend: None of these results remain significant after FDR correction. The recurrent CNVs category represents the neuropsychiatric regions occurring by non-allelic homologous recombination identified in our cohorts. The single genes category represents the neuropsychiatric genes disrupted by a CNV identified in our cohorts. As sensitivity analysis, we removed cases found while bed-sharing or if this information was not available. SUDP: Sudden Unexplained Death in Pediatrics; ASD: autism spectrum disorder; N: number; OR: odds ratio; 95%CI: 95% of confidence interval. John Wiley & Sons, Ltd. 4 Discussion While we and others have successfully identified potentially new genes and mechanisms for SUDP through the use of next-generation sequencing, assessment of structural variation in the genome in SUDP cases has not been extensively reported. Here we report a detailed CMA analysis of 116 well-phenotyped SUDP cases, for which we additionally have completed ES analysis. We identified five cases (4.3%) with pathogenic CNVs and nine (7.8%) with CNVs categorized as VUS favoring pathogenic (total 12.1%). Additionally, we identified two cases of X chromosome duplication consistent with a 47,XXY karyotype and Klinefelter syndrome (2.9% of boys) and one with a 22.7 Mb region of LOH of the X chromosome suggesting possible UPD (0.8%). Two cases with CNVs also had a reportable finding on ES (a pathogenic SCN1A variant in girl case 17 with LOH on chromosome X, and a VUS favoring pathogenic PDHA1 variant in boy case 8 with a duplication on chr13q34). While these ES variants call into question the relevance of the CMA findings in these cases, we cannot rule out the possibility of an additive effect between the CMA and ES findings, particularly since the mechanisms contributing directly to death are not known. Similarly, of the 53 cases (46%) with one or more CNVs categorized as VUS, five had a finding on ES analysis that potentially explained the cause of death. In the only other published study of CNVs in a cohort of SIDS cases, CNVs were detected in 3 of 27 cases (11%), close to our rate of 12.1%. We did not detect any deletions/duplications in the regions described in that study (a 6p22 deletion, an 8q24.3-qter duplication, and a 22q13.3-qter deletion). 4.1 Pathogenic Findings and Structural Variants The varied nature of the phenotypes typically associated with the CNVs detected in our cohort, and the absence or inability to verify many of these features in our cases, raises the question of whether the SUDP deaths in our cohort were related to the CNVs identified. We were unable to perform CMAs on the parents to determine if these CNVs were de novo or inherited, which presents a limitation in assessing pathogenicity. Several of the CNVs that we detected are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, ADHD, and schizophrenia. These include Klinefelter syndrome, NRXN1 deletion, and 15q11.2 deletion syndrome. The association with seizures is of particular interest as there is evidence from our previous studies, as well as others, that seizures and epilepsy are linked to SIDS and SUDC, perhaps as a direct cause of death or perhaps because of a shared pathogenesis due to a heightened susceptibility to other conditions such as arrhythmogenic sudden cardiac death or other mechanism. In Klinefelter syndrome, seizures (febrile, generalized tonic-clonic, focal impaired awareness seizures, and absence) have an estimated prevalence of 5-17%. The two boys with 47,XXY (6 weeks and 3 months of age) were not known to have Klinefelter syndrome prior to birth and had no history of seizures. Additionally, Klinefelter syndrome is associated with an increased risk of adverse fetal and neonatal outcomes, and the rate of neonatal death is 9.5 times higher in Klinefelter syndrome compared to the general population (1.9% vs. 0.2% p < 0.0001), and rates of infant death are more than 50 times higher (5.8% vs. 0.1%, p < 0.0001). The mechanisms for the increased rate of adverse events and deaths in Klinefelter syndrome are not yet determined. Deletions of NRXN1 and the 15q11.2 deletion syndrome are also associated with seizures. To be clear, we were not aware of a history of epilepsy or seizures antecedent to death in our SUDP cases with these findings, but together they raise the question of whether seizure-related mechanisms may have played a role in death, as has been supported by prior evidence from other cases. Klinefelter syndrome, NRXN1 deletion, and 15q11.2 deletion syndrome are associated with ASD and ADHD; NRXN1 deletion and 15q11.2 deletion syndrome are also associated with developmental delay and schizophrenia. Both NRXN1 deletion and 15q11.2 deletion syndrome have incomplete penetrance and variable expressivity. In one study of 15q11.2 deletion syndrome, 81.2% of cases inherited the CNV from one of the parents. Studies have shown that adults with a 15q11.2 deletion have a 90% likelihood of a normal phenotype. As the infants and children in this study with 15q11.2 deletions died prior to the age when psychiatric symptoms would have presented, this makes the interpretation of the impact of the 15q11.2 deletion challenging. 4.2 VUS Findings The relationship to SUDP in the cases with a VUS is unclear. While none of the cases with a CNV interpreted as "pathogenic" had a presumed causative finding on ES, one case in 9 with CNVs interpreted as "VUS favoring pathogenic" had a presumed causative finding on ES, and five of 53 cases with CNVs interpreted as "VUS" had a presumed causative finding on ES (9.4%). 4.3 CNVs over 1 Mb While CNVs larger than 500 kb are found in around 5-10% of individuals, they are found in almost 25% of patients with intellectual disability. Variants greater than 1 Mb are only found in 1-2% of the population. In this cohort, 18% of the total cohort had a CNV larger than 1 Mb. Although the correlation drawn between CNV size and its clinical significance is often true, very large CNVs can be benign in nature and the genome is more polymorphic than previously thought. Therefore, this finding is difficult to interpret. 4.4 Increased Pathogenicity in CNV Deletions Interestingly, we observed a significantly increased pathogenicity score, indicated by the sum of 1/LOEUF, for deletions in our SUDP cohort compared to control cohorts, but not compared to an ASD cohort. These results suggest an overlap between the genetic burden observed in both SUDP and ASD populations. Such similarities are in line with findings from a recent study reporting that genes altered in SUDC are also enriched in lists of genes previously associated with neurodevelopmental disorder, and more particularly with ASD. However, since our cohort was of modest size, replication of this finding with larger and independent samples is paramount. Reproducing such analyses by using a non-neurodevelopmental disorder (e.g., populations with asthma or cancer) as a comparison group would provide more detail on the nature of the CNV burden. 4.5 Limitations One limitation of our study is the relatively small sample size of our cohort, which requires that we interpret the findings with caution. Second, due to the nature of how our cohort was ascertained and consented, we were not able to conduct CMA analyses on the parents of the cases or interview parents directly to obtain additional phenotypic details or family history. Thus, we are unable to determine if CNVs detected were de novo or inherited, which would impact our assessment of their pathogenicity and impact. Another limitation is the completeness of available phenotypic data that is restricted to autopsy material and available medical records. Particular phenotypes, such as cortical thinning in 15q11.2 deletions, are not routinely assessed in autopsy and are not standard phenotyping for well-baby medical visits. Thus, we cannot determine whether the cases had some of the phenotypic characteristics associated with the observed CNV intervals. Additionally, this CMA study focuses on children aged 28 months and younger (average age at death, 5.7 months) and findings may not be generalizable for older children. Finally, the Agilent 4 x 180 array used in this study is unable to detect complex rearrangements, repeat expansions, and balanced translocations. Thus structural variation in these cases would have been missed. 4.6 Conclusions and Recommendations Although we did not find any CNVs that definitively explain the cause of death in our SUDP cohort, our findings suggest new avenues to investigate intrinsic vulnerabilities in the SUDP population. Notably, the pathogenicity score was significantly increased for deletions in comparison to a control database and was similar to the ASD cohort. In addition, several CNVs are associated with neurodevelopmental phenotypes, including two cases with 47,XXY. These findings raise the question of whether the neurodevelopmental or some other consequence of abnormal gene dosage from these CNVs has contributed to death in these cases. In addition, our findings lead to the intriguing question of whether the same causative factors that result in disorders including intellectual disability, ASD, ADHD, and epilepsy (as we have previously reported in the context of SNVs), may also be involved in terminal mechanism contributing to SUDP. The role of neuropsychiatric disease-associated CNVs in SUDP warrants further investigation. Since ES does yet not adequately detect CNVs, when sequencing results are inconclusive, an assessment for CNVs by CMA may provide some answers for families and valuable information on CNVs observed in SUDP cases. The emerging role of CNVs in SUDP warrants further study. In particular, we advocate for dedicated CNV analysis with CMA in cases for which ES is unrevealing, including parental CNV assessment so that de novo versus inherited status can be determined. Future mechanistic studies will allow us to understand the role that specific CNVs may play in sudden death. In concert with past reports of ES findings in SUDP from our group and others, the findings presented here support comprehensive assessment with ES and CMA analysis for all cases of SUDP. Conflict of Interest The authors declare no conflict of interest. Author Contributions C.A.B., E.D., R.D.G., and I.A.H. contributed to the conceptualization and primary writing. C.A.B., E.D., R.L.H., H.Y.K., A.H., C.K., S.A., E.A.H., S.O.V., M.H.W., S.J., A.H.P., R.D.G., and I.A.H. contributed to data collection, analysis and interpretation of results, discussion, review, and editing of the manuscript. Supporting information Supporting Information Click here for additional data file. Acknowledgements R.D.G. and I.A.H. shared last authorship. The authors gratefully acknowledge the patients and families who participated in this study. The authors also acknowledge Dr. Steven Campman for his long-standing history of cooperation with SIDS research. This work was funded by the Robert's Program on Sudden Unexplained Death in Pediatrics, the Jude Zayac Foundation, NIH/NICHD K23HD102589, R01 HD 090064, R01 HD 020991, the Boston Children's Hospital Intellectual and the Developmental Disabilities Research Center Molecular Genetics Core Facility supported by P50HD105351 from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and NIH/NIMH U01 MH119690. Data Availability Statement The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. |
PMC10000289 | Alzheimer's disease (AD) is considered to be the most typical form of dementia that provokes irreversible cognitive impairment. Along with cognitive impairment, circadian rhythm dysfunction is a fundamental factor in aggravating AD. A link among circadian rhythms, sleep, and AD has been well-documented. The etiopathogenesis of circadian system disruptions and AD serves some general characteristics that also open up the possibility of viewing them as a mutually reliant path. In this review, we have focused on different factors that are related to circadian rhythm dysfunction. The various pathogenic factors, such as amyloid-beta, neurofibrillary tangles, oxidative stress, neuroinflammation, and circadian rhythm dysfunction may all contribute to AD. In this review, we also tried to focus on melatonin which is produced from the pineal gland and can be used to treat circadian dysfunction in AD. Aside from amyloid beta, tau pathology may have a notable influence on sleep. Conclusively, the center of this review is primarily based on the principal mechanistic complexities associated with circadian rhythm disruption, sleep deprivation, and AD, and it also emphasizes the potential therapeutic strategies to treat and prevent the progression of AD. Amyloid beta plaques and accumulation of tangles are two major pathological hallmarks of Alzheimer's disease. Due to cholinergic disturbance, HPA axis dysfunction, neuronal loss, and retinal ganglion loss there is disturbance in circadian rhythm which leads to Alzheimer's disease dysfunction. aging Alzheimer''s disease circadian system sleep wake cycle source-schema-version-number2.0 cover-dateMarch 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:10.03.2023 Ahmad F , Sachdeva P , Sarkar J , Izhaar R . Circadian dysfunction and Alzheimer's disease - An updated review. Aging Med. 2023;6 :71-81. doi: 10.1002/agm2.12221 pmc1 INTRODUCTION Alzheimer's disease (AD) is the most common type of neurodegenerative disorder, which largely causes dementia and mainly affects older aged people. By the year 2050, around 12 million cases will be reported. 1 , 2 In AD, accumulation of amyloid beta and hyperphosphorylated tau are microscopic pathologies, whereas reduction in hippocampal volume, frontotemporal, and associated cortical atrophy with ventricular enlargement are macroscopic findings. 3 , 4 , 5 To rule out AD, multiple biomarkers are available, like cerebrospinal fluid (CSF) molecules (for example, amyloid and tau), and to see atrophy in the brain, various neuroimaging techniques, such as computed tomography, magnetic resonance imaging, or positron emission tomography (PET). Current pharmacological treatments include donepezil, galantamine, and rivastigmine, which work as cholinesterase inhibitors. Memantine works as an N-methyl D-aspartate antagonist and Abun approved this in 2021. 6 , 7 Most current studies focus on the molecular aspect of AD, which mainly focuses on neuroinflammation, mitochondrial dysfunction, and glial cell activation. 8 Currently, researchers focus on circadian rhythms, which help the researchers to understand AD pathophysiology in a relatively comprehensive and satisfactory way and also help to address or develop therapeutic targets of AD. Sleep disruptions and circadian disorders are quite common; around 45% of patients face problems with sleep. 9 , 10 These symptoms are present for several patients with AD even before the final medical diagnosis of AD. Based on multiple studies, it is seen that sleep disturbances can lead to neurodegeneration and even cognitive impairment. In the future, it can be utilized as a biomarker for neurodegeneration. In one study, it is seen that older women with diminished and irregular circadian rhythms have a higher risk of developing one of the types of impairments of AD, such as mild cognitive impairment and dementia. Various studies suggest that 25%-66% of patients with AD face sleep disruption, which can be easily noticeable. 11 , 12 , 13 , 14 , 15 , 16 , 17 Melatonin (N-acetyl 5-methoxytryptamine) is a hormone regulated by the circadian rhythms, and it plays a vital role in the neurodegenerative event of AD. 18 The primary source of melatonin is the brain's pineal gland, but other organs like the retina, bone marrow, kidney, pancreas, skin, and glial cells are also involved. Melatonin is a multifunctional hormone that regulates circadian rhythm and shows anti-inflammatory, cytoprotective, and anti-oxidant properties. The circadian clock regulates melatonin and during a study in rat and mice models, melatonin shows the highest plasma melatonin level at midnight. 19 , 20 Melatonin production decreases with aging which can be considered a critical factor for the onset of AD. When impairment or disruption is seen in the suprachiasmatic nucleus (SCN), melatonin levels are reduced, resulting in circadian rhythm disruption. 21 , 22 , 23 Even reduction in CSF is linked with melatonin, and, finally, melatonin progresses AD by causing oxidative damage in the AD brain. Patients with AD have a low level of melatonin as compared with healthy patients. Melatonin can be a promising therapeutic approach to inhibit AD progression as it has free radical scavenging properties as well as anti-amyloidogenic properties. Melatonin also inhibits the secretion process of soluble amyloid precursor protein (APP) in various cell lines through APP maturation. Melatonin administration attenuates amyloid beta generation and deposition in vitro and in vivo models. 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 A sundowning phenomenon enhances mental health decline, confusion, and agitation in patients with AD, whereas melatonin reduces the symptoms of sundowning and enhances cognition. In this review, we discuss the association of circadian dysfunction with AD pathology as well as a few pharmacological and non-pharmacological interventions for sleep disruption in patients with AD. 35 , 36 , 37 , 38 , 39 2 CIRCADIAN BIOLOGICAL CLOCK MECHANISM IN THE BRAIN A core gene of the circadian clock, the Period (PER) gene, was the first clock gene to be discovered by Jeffrey C. Hall and Michael Rosbach. The (PER protein is produced mainly at night and broken down during the day, and this whole cycle is regulated with the help of a negative feedback loop where PER protein blocks its production. 40 , 41 This protein is encoded by the PER gene. Recently, a new gene which is known as the double-time (DBT) gene, has been discovered to encode DBT protein. The DBT protein averts the PER accumulation, proving that rhythm can be flagged according to the 24 hour biological clock. Circadian rhythm regulation is observed both at the central and peripheral levels. In 2017, Jeffrey C. Hall, Michael Rosbash, and Michael Wyong uncovered the molecular mechanisms regulating circadian rhythm and received the Nobel Prize in physiology or medicine. This mechanism demonstrates that mammals have a central pacemaker called the SCN in the hypothalamus. When the retina gets photic input, it transmits information to the SCN. This central clock regulates the circadian rhythm throughout all body functions through the peripheral autonomic nervous system and hormonal factors. The circadian system is a web of interlinked feedback loops and oscillators across all organisms. The Period (PER 1-3), Cryptochrome (CRY1 and 2), and Reverb (NR1D1 and NR1D2) genes are negative feedback regulators which suppress the positive limb. The SCN helps in the synchronization of cellular oscillators across organs in humans. The retina sends light and dark signals to the SCN, which further regulates it. It synchronizes the core clock oscillations in neurons, ultimately translated into oscillatory synaptic output, which transfers the signals to the multiple nuclei in the hypothalamus. All these patterns in neuronal activity, and behavioral and physiological arrhythmicity can be lost post ablation of the SCN. 40 , 41 , 42 , 43 , 44 , 45 The circadian clock system is shown in Figure 1, and relationship between circadian rhythm and AD is shown in Figures 2 and 3. FIGURE 1 Twenty-four hour biological clock in the human brain and its circadian disruption FIGURE 2 Crosstalk between sleep deprivation and Alzheimer's disease. Ab, amyloid beta FIGURE 3 Linkage between circadian rhythm and Alzheimer's disease. Ab, amyloid beta; EEG, electroencephalogram; nREM, non-rapid eye movement; SCN, suprachiasmatic nucleus 3 CHOLINERGIC DISTURBANCES AND CIRCADIAN DYSFUNCTION IN AD PATHOLOGY Neurodegeneration can also be seen in the basal cholinergic forebrain. Disruption in circadian rhythm can also occur due to cells of the nucleus basalis magnocellularis, which projects to the SCN. Enrhardth reported that in rats, there are increased phase delays in response to lights when the cholinergic basal forebrain projects to the SCN. This study suggests a relationship between AD neurodegeneration and the circadian clock's signal entrainment ability. 46 , 47 , 48 4 NEURONAL LOSS IN THE SCN AND CIRCADIAN DYSFUNCTION IN AD During the autopsy of patients with AD, it was seen that there is a neuronal loss in the SCN, which is related to loss of amplitude in the circadian rest-activity pattern. Apart from MT1, melatonin receptor expression was disturbed, which resulted in the SCN responding to the phase resetting signal and generating daily rhythms. 49 , 50 5 RETINAL GANGOLIAN CELL LOSS AND CIRCADIAN DYSFUNCTION IN AD A particular type of subset of retinal ganglion cells (RGCs) known as Melanopsin expressing RGCs (mRGCs) was discovered in 2002. These cells are photoreceptors inside the retina, which help in the photoentrainment of circadian rhythms by projecting light to the SCN. Melanopsin expressing mRGCs constitutes 1%-2% of all RGCs, but they can direct signals to the SCN through the retinal hypothalamic tract. In patients with AD, mRGC loss can be seen, which can cause amyloid beta deposition, and lead to impairment of the entire RGCs even though there is a deposition of amyloid beta in mRGCs. The Toronto study shows interesting results involving retinal amyloid beta deposition in patients with AD. These findings will help better understand the pathology of retinal amyloid beta deposition in patients with AD. Amyloid beta deposition in mRGCs can lead to instability in transmitting the circadian signal of light from the retina to the SCN. 51 , 52 , 53 , 54 , 55 6 CIRCADIAN GENE DELETION AND CIRCADIAN DYSFUNCTION IN AD Deletion mutations in the circadian clock gene cause neuronal injury. Core circadian clock disruption is directly linked to neurodegeneration in AD. BMAL1 is considered to be one of the core genes of the master clock, and a study conducted in mice has shown the deletion of BMAL1 in the hippocampus and cortex. In mice, we observe normal behavioral rhythms and normal sleep wake cycles assessed by wheel running actigraphy and electroencephalogram, respectively, in the presence of severe cortical astrogliosis, synaptic degeneration, and oxidative brain region damage in specific BMAL1 knockout mice. These mice are closely related to transcription multiple redox defenses linked with circadian impairment. Low levels of BMAL1 in the brain also lead to neurodegeneration caused by mitochondrial toxin B nitropropionic acid. The data suggest that decreased BMAL mediated transcriptional exacerbate neurodegeneration in AD. Clock-gene regulation and better insight into the linkage of clock genes and neurodegeneration require further research and a deeper understanding to examine such regulations. 56 , 57 , 58 , 59 The effect of different clock genes on animal models is shown in Table 1. TABLE 1 Effect of different clock genes on different animal models Subject no. Different models Effect of clock genes on different circadian models References 1. APP-PS1 mouse model Casein kinase 1 isoforms e and d with inhibitor PF-670462 reduce amyloid and plaque size as well reduce Ab signal in the prefrontal cortex and hippocampus, which proves chronotherapy as a promising tool to improve behavior in mice 103 2. Two-month-old female APPSwe/PS1dE9 mice Female APPSwe/PS1dE9 mice show abnormal locomotor activity in which clock gene expression of clock genes Per 1, Per 2, Cry 1, and Cry 2 was increased during night time compared to day type in wild type control mice as Cry 1 and Cry2 expression was low in APPSwe /PS1dE9 mice. This study proves APPSwe /PS1dE9 mice as a most promising AD model to test therapeutic agents related to behavioral and circadian rhythm changes. 104 3. Cultured fibroblasts and brain samples BMAL1 is a positive regulator of the circadian clock, and in cultured fibroblasts, DNA methylation regulates BMAL1 rhythms which is linked to circadian alteration in AD 105 4. Tg 4510 mice In Tg4510 mice, it is seen that there is tauopathy in SCN and even disruption in PER2 and BMAL1 in the hypothalamus of Tg4510 mice. This study proves that tauopathy can lead to normal circadian clock function disruption. 106 5. AD brain In this study, the glial fibrillary acid protein in human astrocytes is suppressed as there is an elevation in CLOCK and BMAL, which cause functional impairment by inhibition of aerobic glycolysis in AD 107 6. 5XFAD mouse model Rev-erba, a circadian repressor, decreases amyloid plaque number and size in the 5XFAD AD mouse model. Even Rev-erba show a neuroinflammatory effect, which proves Rev-erba as a novel therapeutic target. 108 7. APP/PS1dE9 mice In APP/PS1dE9 mice, there is an alteration of rhythmic expression patterns of BACE 1 and ApoE in the hippocampus, which is activated by E4BP4 and BMAL1, respectively. So, finally, study suggests that hippocampal clock and circadian oscillation of AD risk gene are regulated by orexin signaling. 109 Abbreviations: Ab, amyloid beta; AD, Alzheimer's disease; SCN, suprachiasmatic nucleus. 7 MICROGLIA, ASTROCYTE, AND CIRCADIAN DYSFUNCTION IN AD Activation of microglia and astrocyte leads to neuroinflammation, which ultimately causes neurodegeneration. Astrocyte activation can be observed to model clock gene deletion in the in vitro model. Even the inflammatory response of microglia leads to variation in the functional circadian clock. Rev-Erb alpha regulates pro-inflammatory cytokine production in macrophages. Finally, inflammation shows the effect of the circadian clock as both Rev-Erb alpha suppressing BMAL1 levels in macrophages in response to lipopolysaccharides. Therefore, the BMAL1 expression in the surrounding glia and neurons can be suppressed by cortex inflammation causing impairment of BMAL1-associated genes, ultimately leading to neurodegeneration. 56 , 60 8 OXIDATIVE STRESS AND CIRCADIAN DYSFUNCTION IN AD PATHOLOGY Numerous studies support the presence of augmented oxidative stress in AD. Less concentration of glutathione and catalase with higher consumption of oxygen (20%-30%) and a higher amount of polyunsaturated fatty acids make the brain a highly vulnerable target for lipid peroxidation. 61 , 62 , 63 Lipids peroxidation interrupts cellular functions, followed by neuronal membrane destruction, and the production of highly reactive electrophilic aldehydes, including acrolein, malondialdehyde, and 4 hydroxy 2-nomial (elevated in AD brains). 64 , 65 , 66 Oxidative stress also damages nucleic acid and proteins. The role of oxidative stress etiology in AD pathogenesis is still unknown. In 1985, the activity of antioxidants, like superoxide dismutase and glutathione peroxidase with oxidative damage in the day-night cycle in the rat cerebral cortex, whereas in humans, anti-oxidants and circadian rhythmicity protect cells from oxidative damage. 67 , 68 , 69 , 70 The levels of glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, uric acid, and peroxiredoxin are high in the morning. In contrast, ascorbic melatonin and plasma level are high in the evening or night. This proves that oxidative stress leads to oxidative damage with the progression of AD, which is ultimately regulated by circadian dysregulation. 71 9 ERK/MARK AND CIRCADIAN DYSFUNCTION IN AD Cognitive impairment is the first symptom observed in AD. Impairment, such as memory, is enhanced by short-term stress and impaired by long-term stress, and the number of dendritic synapses decreases due to high cortisol levels during chronic stress. 72 The pathway primarily revolves around memory consolidation, and the level of phosphor-ERK CAMP, phosphor CREB, and activity of PKA and MEK are associated with a circadian rhythm. Moreover, the SCN regulates the hippocampus' Camp/PKA/ERK/CREB signaling pathway. 73 , 74 , 75 The CREB/ERK/PKA/CAMP signaling pathway increases during rapid eye movement sleep. They are even ablating the BMAL1 gene results in reduced Per1 and PERK levels. A study reported that ERK appears overactivated and memory is improved by pharmacological inhibition of ERK in an AD mouse model, whereas memory impairment is seen due to reduction of pCREB level downstream of the ERK pathway. 76 ERK signaling pathway is disrupted in AD due to amyloid beta 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 bind injury. Finally, ERK/MAPK signaling pathway is a common pathway that causes stress as circadian rhythm even plays a role in memory consolidation. 77 10 HPA AXIS AND CIRCADIAN DYSFUNCTION IN AD HPA axis activation promotes AD pathogenesis. Even reducing cortisol levels by taking dexamethasone does not show positive results in patients with AD; instead of cortisol levels, few approaches to decrease and modulate HPA axis activity can be a promising avenue for treating AD. Even amyloid beta promotes HPA axis activity and increases corticosterone. The HPA axis is one of the common pathways by which SCRD and stress increase amyloid beta production, leading to AD. 78 11 HIPPOCAMPAL VOLUME AND CIRCADIAN DYSFUNCTION IN AD Reduced hippocampal volume was observed in AD and different neurodegenerative and psychiatric disorders. It is hypothesized that prolonged sleep restriction or sleep disruption can cause a decrease in hippocampal neuronal cell proliferation and neuronal cell survival. Few preliminary clinical trials and observational studies suggest that regular physical exercise, cognitive stimulation, and general medical conditions can reduce hippocampal volume or atrophy, reverse hippocampal atrophy, or even expand the hippocampal size. 79 , 80 12 GLYMPHATIC SYSTEM AND CIRCADIAN DYSFUNCTION IN AD The glymphatic system was first described in 2012, which consists of intestinal fluid that regulates brain amyloid clearance by the perivascular space surrounding blood vessels. Glymphatic system dysfunction also plays a vital role in the severity of AD. To date, no clinically approved system has been developed to evaluate the functionality of the glymphatic system in humans. Recently, the glymphatic system has even played a role in glaucoma pathogenesis, characterized by progressive degeneration of RGCs and amyloid beta accumulation. This activity is higher during sleep and low during wakefulness. Even body posture during sleep, especially lateral body position, may increase the rat's glymphatic transport. Further studies need to be done to see the relation of the glymphatic system with patients with AD. 11 , 81 , 82 13 PROTEOSTATIS AND CIRCADIAN DYSFUNCTION IN AD Amyloid beta and tau are specific protein hallmarks seen in AD. Heat shock factor 1 is a type of factor in which deletion alters circulation clock oscillation. Proteasomal degeneration of proteins display oscillations in circadian patterns and expected circadian clock timing requires an understanding of the proteasome function. It is still unknown how the circadian clock controls rhythmic protein degradation in the brain. 83 14 VASCULAR AND CIRCADIAN DYSFUNCTION IN AD Microvascular change is considered an essential factor in the development of AD. Cerebral vascular perfusion is also under the control of the circadian system. According to PET scans and simple-photon emission computed tomography, people with moderate cognitive impairment and an increased risk of developing AD exhibit hypometabolism and cerebral hypoperfusion. Antihypertensive treatment has also been shown to reduce the risk of AD. Brain microvascular changes are critical to AD development, both pathologically and clinically. The circadian system regulates cerebral vascular circulation as well. 84 , 85 , 86 Conroy et al investigated the daily regularity of cerebral blood flow velocity (CBFV) across 30 hours of continuous awake time. The findings of this study suggested that human CBFV probably follows an endogenous circadian rhythm, which will be investigated further in the context of cerebrovascular/cardiovascular events and cognitive function deterioration. 87 , 88 , 89 Laser-Doppler flowmetry revealed similar results in rats. The cerebral blood flow has a diurnal periodicity independent of locomotor activity and blood pressure changes. The effect of the circadian rhythm on brain metabolism and perfusion should be carefully considered in future studies on the role of vascular function in AD etiopathogenesis. 90 , 91 , 92 15 METABOLIC CHANGES AND CIRCADIAN DYSFUNCTION IN AD Circadian/sleep disruption may be mediated by metabolic changes in neurodegenerative disorders, particularly AD. Insulin resistance has been linked to an increased risk of AD in clinical studies, and childhood obesity can also cause cognitive impairment later in life apart from diabetes. Apolipoprotein E (APOE) is a key regulator of lipid metabolism found primarily in brain astrocytes. The APOE 4 allele can cause mitochondrial dysfunction, leading to insulin resistance and metabolic defects as a major risk factor for AD. 93 , 94 , 95 , 96 , 97 , 98 A recent study suggests that peripheral metabolic dysfunction plays a role in the development of AD-related neuropathology. The clock regulates the majority of metabolic activity, and the loss of circadian clocks has been linked to cellular and system-wide metabolic deficits. Sleep deprivation significantly impacts metabolism, including an increase in insulin resistance markers. Based on these findings, it is enticing to believe that sleep disruption increases the risk of AD by disrupting metabolism. 99 , 100 , 101 , 102 16 MELATONIN AS A PROMISING THERAPEUTIC TARGET FOR AD In AD, melatonin has shown multiple beneficial effects, like prevention of mitochondrial dysfunction, inhibition of amyloid beta toxicity, free radical scavenging, and even circadian dysregulation like sundowning and sleep disturbances. 110 Melatonin even has blood-brain barrier crossing capacity, anti-oxidant properties, as well as balanced amphiphilicity. Amyloid beta peptides are mainly produced with the help of amyloidogenic beta-amyloid precursor protein (beta APP). Amyloid beta 42 is the most neurotoxic form of amyloid beta. This beta pleated sheet peptide ultimately forms an aggregation of senile plaques in the brain in the form of amyloid fibrils that disrupts synaptic communications leading to abnormal function of neurons and neuronal death. As melatonin has anti-oxidant, neuroprotective, and anti-amyloidogenic properties, it might help in decreasing amyloid beta formation. Melatonin has shown effects on both in vivo and in vitro models. 111 , 112 , 113 , 114 , 115 Hyperphosphorylated tau plays a crucial role in dealing with memory and cognitive impairment in AD. Neurodegeneration happens due to tau hyperphosphorylation. This tau phosphorylation and protein kinase A (PKA) overactivation in the isopropanol-induced rat brain can be attenuated by melatonin. This process is followed in the neuroblastoma SHSY5Y cell line and N2a induced by calyculin A, okadaic acid, and wortmannin. Melatonin shows neuroprotective effects in the degeneration of the hippocampus and enhances cognitive effects. These effects are displayed through regulating GSK3 and CDK5 activities in hippocampal neurons. Melatonin inhibits the expression level of caspase 3, prostate apoptosis response 4 (Par4), and Bcl2 associated BAX, reducing neuronal death. 116 , 117 , 118 , 119 , 120 , 121 Melatonin has an anti-oxidant property that reduces oxidative stress. In an experimental study, it was observed that NF-KB commenced IL-6 in amyloid beta treated brain slices can be inhibited by melatonin in a concentration-dependent fashion. Melatonin injection (ie, 5 mg/kg, 0.1 to 10 mg/kg, and 10 mg/kg) in the rat in which melatonin shows anti-inflammatory effects and reduces neuroinflammation by increasing ATP production, stimulating GPX activities, and even enhances SOD activity. 122 Therefore, this evidence shows the anti-neuroinflammatory effects of melatonin on AD. 17 RELATION AMONG EXERCISE, CIRCADIAN RHYTHM, AND AD Various animal models show exercise chronobiotic properties. It is difficult to identify whether exercise has chronobiotic properties in humans because it is quite hard to differentiate the range of effects shown by exercise from multiple other factors, like food, social influences, and light. 123 Non-photic stimuli, on the other hand, appear to be capable of synchronizing circadian rhythms in people who are blind who lack sensitivity to light, and this helps them entrain to routine schedules without utilizing exogenous melatonin. A recent study related to circadian rhythms and AD has shown that when a person exercises just before habitual sleep, it accelerates circadian rhythm and if it is performed during habitual sleep time, it delays circadian rhythms. 124 , 125 , 126 Exercise also affects the hippocampus, which plays a role in affecting sleep quality. It has also been reported that people who do exercise regularly on a daily basis have better sleep quality as well as less daytime sleepiness when compared to people who are inactive and do not exercise. As a result, it is still possible that exercise has a greater impact on older adults who face difficulty in sleeping. Exercises also enhance the cognitive part and show neural plasticity which is effective in normal aging as well as a treatment for AD. 127 , 128 , 129 , 130 , 131 , 132 Sleep after exercise has a well-known effect on cognitive performance. According to the recent study findings, physical activity plays a huge role in diminishing the effects of poor sleep quality on cognitive functioning in older adult women. As a result, more research is needed to understand the mechanisms underlying exercise, sleep, and cognitive function that are linked in older adults. 133 , 134 , 135 , 136 , 137 , 138 18 CURRENT THERAPIES AND FUTURE IMPLICATIONS Unfortunately, at present, we have limited pharmacological and non-pharmacological interventions to manage sleep disturbance in patients with AD. In AD, current behavioral practices include limited caffeine and alcohol intake, regular exercise, and maintaining regular bed and wake times with ample light exposure upon waking. 60 Sufficient daytime light exposure is crucial for patients with AD, mainly for institutionalized patients. Consistent light exposure may bring changes in dysfunctional circadian rhythms in AD and reduce the "sundowning." Patients with moderate-to-severe AD were included in the melatonin and trazodone trials, but only patients with mild-to-moderate AD were included in the ramelteon study. Melatonin is considered a part of various clinical manifestations and treatment strategies of AD. 139 , 140 , 141 Actigraphy is used to measure all primary sleep outcomes. Despite the absence of severe side effects, we still have no evidence to suggest that melatonin and trazodone improve sleep quality. More comprehensive clinical trials are desperately needed in this area, particularly those focusing on sleep and cognitive or pathological outcomes in AD. Suvorexant is the first US Food and Drug Administration (FDA)-approved orexin receptor antagonist which can show effects on amyloid deposition and cognitive end points in early-stage or presymptomatic AD. Melatonin supplementation on a regular basis may help patients with mild cognitive impairment improve their cognitive performance slightly. However, there appears to be conflicting evidence in mice regarding the effectiveness of melatonin supplementation in reducing amyloid plaques and other AD correlates. Ramelteon has been approved for insomnia, whereas tasimelteon is for the treatment of non-24 hour sleep-wake disorder in the blind. Until now, these two drugs have not been tested for AD but can be more effective than melatonin. Researchers are trying to develop a drug that can directly target the circadian clock, although they are still in the early stages of development. Small molecules that can alter circadian oscillations' amplitude, frequency, and period have been discovered through high throughput screening. RevErb is a small molecule agonist of the nuclear receptor that can improve metabolic function in mice by directly affecting circadian rhythms. Finally, the right targeting of the circadian clock could be a promising remedial option for treating AD. 33 , 34 19 CONCLUSION The pathology of AD (amyloid and tau) has been linked to circadian dysfunctions, and sleep disruptions are very common in patients with Alzheimer's disease that play an important role in disease succession and pathology. Moreover, circadian rhythms communicate with nearly all systems and risk factors involved in the growth and progression of AD. Recognizing early signs of AD, such as changes in sleep patterns and rest-activity rhythm anomalies, could be useful in identifying early biomarkers for interference to prevent the formation of amyloid-beta, neurofibrillary tangles and the succession of neurodegeneration. In patients with advanced AD, bright light therapy combined with chronobiotics is effective in treating sundowning characteristics and other cognitive symptoms. Future research into the function of circadian misalignment in the initial stages of AD could lead to new preventive and therapeutic approaches. As a result, circadian rhythms are an excellent target for combating pathology. AUTHOR CONTRIBUTIONS Manuscript writing and drawing figures: Faizan Ahmad. Manuscript writing, reviewing, and editing: Punya Sachdeva. Editing: Jasmine Sarkar. Reviewing: Rafiah Izhaar. FUNDING INFORMATION No funding was received for this study. CONFLICT OF INTEREST The authors declare they have no conflict of interest. |
PMC10000290 | Front Chem Front Chem Front. Chem. Frontiers in Chemistry 2296-2646 Frontiers Media S.A. 1132587 10.3389/fchem.2023.1132587 Chemistry Original Research Anti-Kekule number of the {(3, 4), 4}-fullerene* Yang and Jia 10.3389/fchem.2023.1132587 Yang Rui * Jia Huimin School of Mathematics and Information Science, Henan Polytechnic University, Jiaozuo, Henan, China Edited by: Baoyindureng Wu, Xinjiang University, China Reviewed by: Guifu Su, Beijing University of Chemical Technology, China Qiuli Li, Lanzhou University, China Hong Bian, Xinjiang Normal University, China *Correspondence: Rui Yang, [email protected] This article was submitted to Theoretical and Computational Chemistry, a section of the journal Frontiers in Chemistry 24 2 2023 2023 11 113258727 12 2022 06 2 2023 Copyright (c) 2023 Yang and Jia. 2023 Yang and Jia This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. A {(3,4),4}-fullerene graph G is a 4-regular plane graph with exactly eight triangular faces and other quadrangular faces. An edge subset S of G is called an anti-Kekule set, if G - S is a connected subgraph without perfect matchings. The anti-Kekule number of G is the smallest cardinality of anti-Kekule sets and is denoted by akG . In this paper, we show that 4<=akG<=5 ; at the same time, we determine that the {(3, 4), 4}-fullerene graph with anti-Kekule number 4 consists of two kinds of graphs: one of which is the graph H1 consisting of the tubular graph Qnn>=0 , where Q n is composed of nn>=0 concentric layers of quadrangles, capped on each end by a cap formed by four triangles which share a common vertex ; and the other is the graph H2 , which contains four diamonds D 1, D 2, D 3, and D 4, where each diamond Di1<=i<=4 consists of two adjacent triangles with a common edge ei1<=i<=4 such that four edges e 1, e 2, e 3, and e 4 form a matching . As a consequence, we prove that if GH1 , then akG=4 ; moreover, if GH2 , we give the condition to judge that the anti-Kekule number of graph G is 4 or 5. anti-Kekule set anti-Kekule number {(3,4),4}-fullerene perfect matching matching National Natural Science Foundation of China 10.13039/501100001809 11801148 11626089 This work was supported by the National Natural Science Foundation of China (grant nos. 11801148 and 11626089) and the Foundation for the Doctor of Henan Polytechnic University (grant no. B2014-060). pmc1 Introduction A {(3,4),4}-fullerene graph G is a 4-regular plane graph with exactly eight triangular faces and other quadrangular faces. This concept of the {(3, 4), 4}-fullerene comes from Deza's {(R,k)}-fullerene (Deza and Sikiric, 2012). Fixing R N, a {(R, k)}-fullerene graph is a k-regular k>=3 , and it is mapped on a sphere whose faces are i-gons iR . A {(a,b),k}-fullerene is {(R, k)}-fullerene with R=a,b1<=a<=b . The {(a, b), k}-fullerene draws attention because it includes the mostly widely researched graphs, such as fullerenes (i.e.,{(5, 6), 3}-fullerenes), boron-nitrogen fullerenes (i.e.,{(4, 6), 3}-fullerenes), and (3,6)-fullerenes (i.e.,{(3, 6), 3}-fullerenes) (Yang and Zhang, 2012). The anti-Kekule number of a graph was introduced by Vukicevic and Trinajstic (2007). They introduced the anti-Kekule number as the smallest number of edges that have to be removed from a benzenoid to remain connected but without a Kekule structure. Here, a Kekule structure corresponds to a perfect matching in mathematics; it is known that benzenoid hydrocarbon has better stability if it has a lower anti-Kekule number. Veljan and Vukicevic (2008) found that the anti-Kekule numbers of the infinite triangular, rectangular, and hexagonal grids are 9, 6 and 4, respectively. Zhang et al. (2011) proved that the anti-Kekule number of cata-condensed phenylenes is 3. For fullerenes, Vukicevic (2007) proved that C 60 has anti-Kekule number 4, and Kutnar et al. (2009) showed that the leapfrog fullerenes have the anti-Kekule number 3 or 4 and that for each leapfrog fullerene, the anti-Kekule number can be established by observing the finite number of cases independent of the size of the fullerene. Furthermore, this result was improved by Yang et al. (2012) by proving that all fullerenes have anti-Kekule number 4. In general, Li et al. (2019) showed that the anti-Kekule number of a 2-connected cubic graph is either 3 or 4; moreover, all (4,6)-fullerenes have the anti-Kekule number 4, and all the (3,6)-fullerenes have anti-Kekule number 3. Zhao and Zhang (2020) confirmed all (4,5,6)-fullerenes have anti-Kekule number 3, which consist of four sporadic (4,5,6)-fullerenes (F 12, F 14, F 18, and F 20) and three classes of (4,5,6)-fullerenes with at least two and at most six pentagons. Here, we consider the {(3, 4), 4}-fullerene graphs. In the next section, we recall some concepts and results needed for our discussion. In Section 3, by using Tutte's Theorem on perfect matching of graphs, we determine the scope of the anti-Kekule number of the {(3, 4), 4}-fullerene. Finally, we show that the {(3, 4), 4}-fullerene with anti-Kekule number 4 consists of two kinds of graphs H1,H2 . As a consequence, we prove that if GH1 , then akG=4 . Moreover, if GH2 , we give the condition to judge that the anti-Kekule number of graph G is 4 or 5. 2 Definitions and preliminary results Let G=V,E be a simple and connected plane graph with vertex set V(G) and edge set E(G). For V'VG , G - V' denotes the subgraph obtained from G by deleting the vertices in V' together with their incident edges. If V' = v, we write G - v. Similarly, for E'EG , G - E' denotes the graph with vertex set V(G) and edge set EG-E' . If E' = e, we write G - e. Let V' be a non-empty set; GV' denotes the induced subgraph of G induced by the vertices of V'; similarly, if E'EG , GE' denotes the induced subgraph of G induced by the edges of E'. For a subgraph H of G, the induced subgraph of G induced by vertices of VG-VH is denoted by H . A plane graph G partitions the rest of the plane into a number of arcwise-connected open sets. These sets are called the faces of G. A face is said to be incident with the vertices and edges in its boundary, and two faces are adjacent if their boundaries have an edge in common. Let FG be the set of the faces of G. An edge-cut of a connected plane graph G is a subset of edges CEG such that G - C is disconnected. A k -edge-cut is an edge-cut with k edges. A graph G is k -edge-connected if G cannot be separated into at least two components by removing less than k edges. An edge-cut C of a graph G is cyclic if its removal separates two cycles. A graph G is cyclically k -edge-connected if G cannot be separated into at least two components, each containing a cycle, by removing less than k edges. A cycle is called a facial cycle if it is the boundary of a face. For subgraphs H 1 and H 2 of a plane graph G, EH1,H2=EVH1,VH2 represents the set of edges whose two end vertices are in VH1 and VH2 separately. If VH1 and VH2 are two non-empty disjoint vertex subsets such that VH1VH2=VG , then EH1,H2 is an edge-cut of G, and we simply write H1=VH1 or H2=VH2 . We use G to denote the boundary of G, that is, the boundary of the infinite face of G. A matching M of a graph G is a set of edges of G such that no two edges from M have a vertex in common. A matching M is perfect if it covers every vertex of G. A perfect matching is also called a Kekule structure in chemistry. Let G be a connected graph with at least one perfect matching. For SEG , we call S an anti-Kekule set if G - S is connected but has no perfect matchings. The smallest cardinality of anti-Kekule sets of G is called the anti-Kekule number and denoted by akG . For the edge connectivity of the {(3, 4), 4}-fullerene, we have the following results. Lemma 2.1 ((Yang et al., 2023) Lemma 2.3) Every {(3, 4), 4}-fullerene is cyclically 4-edge-connected. Lemma 2.2 ((Yang et al., 2023) Corollary 2.4) Every {(3, 4), 4}-fullerene is 4-edge-connected. Q n is the graph consisting of n concentric layers of quadrangles, capped on each end by a cap formed by four triangles which share a common vertex as shown in Figure 2. In particular, Q 0 is what we call an octahedron . Lemma 2.3 ((Yang et al., 2023) Lemma 2.5) If G has a cyclical 4-edge-cut E=e1,e2,e3,e4 , then GQnn>=1 , where the four edges e 1 , e 2 , e 3 , and e 4 form a matching, and each e i belongs to the intersection of two quadrilateral faces for i = 1, 2, 3, 4. Tutte's theorem plays an important role in the process of proof. Theorem 2.4 (Lovasz and Plummer, 2009) (Tutte's theorem) A graph G has a perfect matching if and only if for any XVG , oG-X<=X , where oG-X denotes the number of odd components of G - X . Here, an odd component of G - X is trivial if it is just a single vertex and non-trivial otherwise. All graph-theoretical terms and concepts used but unexplained in this article are standard and can be found in many textbooks, such as Lovasz and Plummer (2009). 3 Main results From now on, let G always be a {(3, 4), 4}-fullerene; we called a 4-edge-cut E in G trivial if E=v , that is, E consists of the four edges incident to v. By Lemma 2.3, if E is a cyclical 4-edge-cut, then the four edges in E form a matching. Moreover, if E is not a cyclical 4-edge-cut, then E is trivial. So, we have the following lemma. Lemma 3.1 Let G be a {(3, 4), 4}-fullerene, E=e1,e2,e3,e4 be an 4-edge-cut, but it is not cyclical, then E is trivial. Proof Since E=e1,e2,e3,e4 is an 4-edge-cut, G - E is not connected. Then, G - E has at least two components. Moreover, as G is 4-edge-connected by Lemma 2.2, G - E has at most two components. So, G - E has exactly two components. Let G 1, G 2 be two components of G - E. Since E is not cyclical, without loss of generality, we suppose that G 1 is a forest; then, we have n-e=l, (1) where n, e, l is the number of vertices, edges, and trees in G 1, respectively. Furthermore, since each vertex of G is of degree 4, we have 4n-4=2e. (2) Combing with equalities 1) and 2), we know n = l = 1 and e = 0, which means G 1 only consists of a single vertex. So, E is trivial. # Lemma 3.1 plays an important role in the proof of the following theorem. Next, we explore the scope of the anti-Kekule number of {(3, 4), 4}-fullerene. Theorem 3.2 Let G be a {(3, 4), 4}-fullerene, then 4<=akG<=5 . Proof First, we show akG<=5 . Let t be any triangle in G and the boundary of t was labeled v 1 v 2 v 3 along the clockwise direction. Denote the other two edges incident to v1v2 by e1,e2e4,e5 , set e 3 = v 1 v 2, then e 1, e 2, e 3, e 4, and e 5 are pairwise different, set E'=e1,e2,e3,e4,e5 and G' = G - E'. In order to show akG<=5 , we only need to prove that G' is connected and has no perfect matchings. Then, G' has no perfect matchings since the two edges v 1 v 3, v 2 v 3 cannot be covered by a perfect matching at the same time in G'. In the following, we show that G' is connected. We proved this using reduction to absurdity, suppose G' is not connected, then G' has a component (say G 1) containing vertices v 1, v 2, and v 3, as v 1, v 2, and v 3 are connected by the path v 1 v 3 v 2 in G 1. On the other hand, since e 3 = v 1 v 2 connects two vertices v 1, v 2 in G and E'=e1,e2,e3,e4,e5 is an edge cut of G, even if we remove five edges, e 1, e 2, e 3, e 4, and e 5, to disconnect G, it is actually the same as removing four edges, e 1, e 2, e 4, and e 5 ; that is, E1=e1,e2,e4,e5 is an 4-edge-cut. Moreover, due to Lemma 2.3, E 1 cannot be a cyclical 4-edge-cut as e 1, e 2, e 4, and e 5 is not a matching. Then, according to Lemma 3.1, E 1 is a trivial 4-edge-cut. Thus, G 1 or G1 is a single vertex, both of which are impossible by the definition of G. So G' is connected. Thus, akG<=5. (3) Finally, we show akG>=4 . By the definition of an anti-Kekule set, suppose E1'=e1',e2',e3',...,ek' was the smallest anti-Kekule set of G, that is, akG=k . Then, G1'=G-E1' was connected and has no perfect matching. Hence, according to Theorem 2.4, there exists a non-empty subset X0VG1' such that oG1'-X0>X0 , since VG1'=VG and VG is even, oG1'-X0 and X0 have the same parity. Consequently, oG1'-X0>=X0+2 (4) For the sake of convenience, we let a=oG1'-X0 . If we chose an X 0 with the maximum size, then G1'-X0 has no even components. On the contrary, we suppose there exists an even component (say F) of G1'-X0 . For any vertex vVF , oF-v>=1 . Let X'=X0v , thus oG1'-X'=oG1'-X0+oF-v>=X0+2+1=X'+2 , which is a contradiction to the choice of X 0. In addition, E1' is the smallest anti-Kekule set of G, then G1'+ei' has perfect matchings for any edge ei'E1' for 1 <= i <= k. On the other hand, the number of odd components of G1'-X0 was not decreased or decreased by at most one or two if we add one edge ei' to G1' , that is, X0>=oG1'+ei'-X0>=a-2. (5) By inequality (4), we have X0<=a-2. (6) Combined with inequalities (5) and (6), we have a=X0+2 and each edge ei'E1' connects two odd components of G1'-X0 . Let H 1, H 2, H 3, ..., H a be the odd components of G1'-X0 . Then, due to Lemma 2.2, Hi>=41<=i<=a ; therefore, 4a-2k<=i=1aHi-2E1'<=4X0=4a-2. (7) Thus, k >= 4, that is, akG>=4 . We know that 4<=akG<=5 . By Theorem 3.2, we know that 4<=akG<=5 . Next, we give the characterization of {(3, 4), 4}-fullerenes with anti-Kekule number 4. Before, we define H1=Qnn>=0 , where Q n is shown in Figure 2. The structure of two adjacent triangles is called a diamond. In a diamond, the common edge of the two triangles is called the diagonal edge. The subgraph consisting of four diamonds such that the four diagonal edges form a matching is denoted by D, that is, D=i=14Di . Let H2=G|DG . So, we have the following theorem. FIGURE 1 Edges e 1 e 2, e 3, e 4, and e 5. FIGURE 2 {(3,4),4}-Fullerene Q n , where the bold segments indicate the cap of Q n (n >=0). Theorem 3.3 Let G be a {(3, 4), 4}-fullerene, if akG=4 , then GH1 or GH2 . Proof Let E 0 be the anti-Kekule set of G such that E0=4 , set G 0 = G - E 0. Then, G 0 is connected without perfecting matchings. Thus, by Theorem 2.4, there exists a non-empty subset X0VG0 such that oG0-X0>X0 . For convenience, let a=oG0-X0 , since a and X0 have the same parity, that is, a>=X0+2. (8) We choose an X 0 satisfying Ineq. (8) with the maximum size. Then, a proof similar to the proof of Theorem 3.2 is used to prove akG>=4 . We can know G 0 - X 0 has no even components. Let H 1, H 2, H 3, ..., H a be all the odd components of G 0 - X 0, set H=i=1aHi . Let H 1, H 2, H 3, ..., H b be the non-trivial odd components of G 0 - X 0, set H*=i=1bHi . Let H b+1, H b+2, H b+3, ..., H a be the trivial odd components of G 0 - X 0, set H0=i=b+1aHi . Then, VG is divided into X 0, VH* , VH0 . Since akG=4 , all equalities in Ineq. (7) of Theorem 3.2 hold. The first equality in Ineq. (7) holds if and only if Hi=41<=i<=a , and the second equality in Ineq. 7) holds if and only if there is no edge in the subgraph G0X0 ; that is, X 0 is an independent set of G 0. Moreover, each edge of E 0 connects two components in H and X0=a-2 . Since Hj=41<=j<=a , Hj is a cyclical 4-edge-cut of G or not. Next, we distinguish the following two cases to complete the proof of Theorem 3.3. Case 1: There exists one H j such that Hj is a cyclical 4-edge-cut. By Lemma 2.3, GQnn>=1 , which means the four edges of Hj form a matching. Without loss of generality, we supposed H j consists of s layers of quadrangular faces and the cap of H j is entirely in the interior of the boundary cycle Hj . Then, GVHj Hj induced by the vertices of Hj and the boundary of Hj consists of n - s layers of quadrangular faces and a cap, for convenience, set m = n - s, let L 1, L 2, L 3, ..., L m be all the layers and C be the cap of GVHj Hj , where quadrangular layer L i is adjacent to L i-1 and L i+1 for 2 <= i <= m - 1, L 1 is adjacent to H j , and L m is adjacent to C. Set R 1 = H j L 1 and R m+1 = C L m . For 2 <= i <= m, let R i = L i-1 L i . The vertices on Rii=1,2,3,...,m+1 are recorded as v i1, v i2, v i3, and v i4 (i = 1, 2, 3, ..., m + 1) in a clockwise direction and v i1, v i3, and v i2, v i4, are on the same line, respectively . Since Hj is a cyclical 4-edge-cut, set (Hj)={e1',e2',e3',e4'} . Without loss of generality, set ei'=v1iv2i(1<=i<=4) . The vertices shared by the four triangles on the two caps are represented by v', v '', respectively, such that v' is in H j and v '' is in Hj . Next, we analyze whether the edges of Hj belongs to E 0 or not, which is divided into the following five subcases. Subcase 1.1: All the edges of Hj belong E 0. That is, ei'E0 for all i = 1, 2, 3, 4. Since each edge of E 0 connects two components of H and there are four edges e1',e2',e3',e4' belonging to E 0. All the vertices of Hj belong to VH* , which means X 0 = , a contradiction. Subcase 1.2: Exactly three edges of Hj belong to E 0. Without loss of generality, suppose e1',e2',e3'E0 , then v 24 X 0 and v21,v22,v23VH , that is, v 21, v 22, v 23 belong to VH* or VH0 . If all of v 21, v 22, and v 23 belong to VH0 , then v 21 v 22, v 22 v 23 E 0, immediately E0>4 , which contradicts E0=4 . This contradiction means at least one of v 21, v 22, and v 23 belongs to VH* (say VH1 ), then by Lemma 2.3 and Lemma 3.1, either H1 is a cyclical 4-edge-cut and the four edges in H1 form a matching or H1 is trivial. However, since H 1 is a non-trivial odd component of G 0 - X 0, VH1>=3 . Thus, H1 is not a trivial 4-edge-cut. That is, H1 is a cyclical 4-edge-cut, and the four edges in H1 form a matching. Now, if v 21 (or v 23) belong to VH1 , then v 21 v 24, v 21 v 11 (or v 23 v 24, v 23 v 13) belong to H1 , but they do not form a matching, a contradiction. Thus, both v21,v23VH0 and v22VH1 . Immediately, we have v 21 v 22, v 22 v 23 E 0 and E0>4 , which contradicts E0=4 . This contradiction means there cannot be three edges of Hj belonging to E 0. Subcase 1.3: Exactly two edges of Hj belong to E 0. Then, by symmetry, e1',e2'E0 or e1',e3'E0 . First, if e1',e2'E0 , then v 23, v 24 X 0 and v23v24EX0 , which contradicts that EX0= . Claim 1: For a quadrangular face q with q=abcda with clock direction such that aX0,bVH0 , then c,dVH0 or c,dVH* or cX0,dVH0 . FIGURE 3 VG is divided into X 0, VH* , and VH0 . FIGURE 4 Labeling of GVHj Hj . Proof Since EX0= , dVH0VH* . If dVH0 , then cVH* by Lemma 2.3 and Lemma 3.1, thus c X 0 or cVH0 . If dVH* , then also by Lemma 2.3 and Lemma 3.1, we can know cVH* and the claim holds. By Claim 1, next, if e1',e3'E0 , then v22,v24VX0 , v21,v23VH . If all the vertices of v 21, v 22, v 23, and v 24 belong to the cap of Hj , that is, all of v 21, v 22, v 23, and v 24 are adjacent to v '', then as E0=4 and e1',e3'E0 , we can know v '' H 0 and v 21 v '', v 23 v '' E 0, and we have the {(3, 4), 4}-fullerenes Q s+1, that is, m = 1. If all the vertices of v 21, v 22, v 23, and v 24 do not belong to the cap of Hj , that is, the layer L 2 consists of four quadrangular faces, then, for the quadrangular face qFL2 , the vertices on q belong to X 0, H 0, H 0, H 0 or X 0, H 0, H*, H* or X 0, H 0, X 0, H 0 by Claim 1. If the former case holds, that is, there exists one face qFL2 such that the boundary of q is of the form X 0, H 0, H 0, and H 0, then immediately we can have E0>4 , a contradiction. If the second case holds, that is, there exists one face qFL2 such that the boundary of q is of the form X 0, H 0, H*, and H*, then by Claim 1 and since E0=4 , we can know all the faces of L 2 are of the form X 0, H 0, H*, and H*, that is, all the vertices of HjL1 belong to VH* . In this case, we also have GH1 . By the aforementioned discussion and Claim 1, next, we suppose all the quadrangular faces of L 2 are of the form X 0, H 0, X 0, and H 0. Then, we can use the aforementioned same analysis to the layer L 3 as L 2, since G Q n and H j consists of s layers of quadrangular faces; after finite steps (say t steps), we obtain t layers L 2, L 3, ..., L t+1 such that all the faces of Li2<=i<=t+1 are of form X 0, H 0, X 0, and H 0 and either the four vertices on Rt+2 are adjacent to v''(v''VH0) or all the vertices of HjL1L2Lt+1 belong to VH* . If the four vertices on Rt+2 are adjacent to v''(v''VH0) , then m = t + 1, n = s + t + 1 and GH1 . If all the vertices of HjL1L2Lt+1 belong to VH* (say VH1 ), suppose H 1 consists of p layers of quadrangular faces, then m = t + p + 2, n = s + t + p + 2, and also GH1 . To sum up, if exactly two edges of Hj belong to E 0, then GH1 . Subcase 1.4: Exactly one edge of Hj belong to E 0. Without loss of generality, suppose e1'E0 , then v 22, v 23, v 24 X 0, v22v23,v23v24EX0 , which contradicts that X 0 is an independent set of G 0. Subcase 1.5: No edge of Hj belongs to E 0. Thus, i=14v2iX0 , so v21v22,v22v23,v23v24,v24v21EX0 , which contradicts EX0=ph . Case 2: Hj is not a cyclical 4-edge-cut of G for all 1 <= j <= a. For convenience, set E0=e1,e2,e3,e4 . Here, first, we give the idea of proof, then we will show that G 0 = G - E 0 is bipartite by proving VHi=11<=i<=a . Since G has exactly eight triangular faces and E0=4 , which implies that each edge e i of E 0 is the common edge of two triangles, by discussing all possible subgraphs formed by facial cycles containing an edge of E 0, we show that GH1 or GH2 . Since Hj is not a cyclical 4-edge-cut of G for all 1 <= j <= a, H j or Hj is a singleton by Lemma 3.1. Since X 0 is non-empty and a=X0+2 , which means H j is a singleton vertex, that is, VHj=11<=j<=a . Let Y 0 denote the set of all singletons y i from each Hi1<=i<=a , and denote the vertices of X 0 by xi1<=i<=X0 , so G0=X0,Y0 is bipartite. For convenience, we color the vertices white in X 0 and black in Y 0. Next, we consider possible subgraphs of G containing all edges of E 0. By the Euler theorem, G has exactly eight triangular faces because G0=X0,Y0 is bipartite; each edge e i of E 0 is the common edge of two triangles and connects two vertices in Y 0, that is, every edge e i E 0 belongs to a diamond, say D i , i = 1, 2, 3, 4 and FDiFDj=ij,i,j=1,2,3,4 . Claim 2: If GE0 has one component, then G Q 0, where Q 0 is the octahedron. Proof If GE0 has one component, then we have the subgraphs shown in Figures 5A, B, C) if GE0 is a tree and Figures 5D, E if GE0 has cycles. If GE0 is isomorphism to the graph shown in Figure 5A, then the two diamonds D 1, D 2 are adjacent and they form one cap of Q n . Set D 12 = D 1 D 2, then D12 forms an 4-edge-cut. On the other hand, by Lemma 2.3 and Lemma 3.1, D12 is a cyclical 4-edge-cut and G Q p or D12 is trivial. If D12 is a cyclical 4-edge-cut, then GQpp>=1 and e 3 belongs to a quadrangular face, which contradicts that the two faces containing e 3 are triangles. If D12 is a trivial 4-edge-cut, that is, D12 is a singleton, which is impossible as the two vertices of e 4 belong to VD12 . Thus, GE0 cannot be isomorphism to the subgraph shown in Figure 5A. All the situations of Figures 5B-D contradicts FDiFDj=ij,i,j=1,2,3,4 . If GE0 is isomorphic to the graph shown in Figure 5E, then in order to guarantee FDiFDj=ij,i,j=1,2,3,4 , the four diamonds D 1, D 2, D 3, and D 4 forms two caps of Q n such that the cycle induced by E 0 is exactly the intersecting of the two caps. Immediately, we have the graph Q 0 , that is, G Q 0 if GE0 has one component, so GH1 . In accordance with Claim 2, next, we assume that GE0 is not connected, so GE0 has at least two and at most four components. Then, we have the following three cases. Subcase 2.1: GE0 has exactly two components. By symmetry, the subgraph induced by E 0 has four cases as shown in Figures 6A-D. Then, the graph G which contains the subgraphs shown in Figure 6B contradicts FDiFDj=ij,i,j=1,2,3,4 . If G contains the subgraph shown in Figure 6C, then the three edges e 1, e 2, and e 3 belong to the same triangular face as every 3-length cycle of a {(3, 4), 4}-fullerene must be the boundary of a triangular face by Lemma 2.2, which contradicts that FDiFDj=ij,i,j=1,2,3,4 . If GE0 is isomorphic to the graph as shown in Figure 6A, then the three edges e 1, e 2, and e 3 belong to three diamonds D 1, D 2, and D 3, respectively, and we have the subgraph A 1 consisting of D 1, D 2, and D 3 such that A1=2 and A 1, D 4 are disjoint. By the definition of G, we can know the two 3-degree vertices on A1 must be adjacent and we obtain G Q 0, which contradicts that A 1, D 4 are disjoint. If GE0 is isomorphic to the graph as shown in Figure 6D, then D 1, D 2 are adjacent, and D 3, D 4 are adjacent. Set B 1 = D 1 D 2, B 2 = D 3 D 4. Since the two edges e 1, e 2 are disjoint, the edges e 3, e 4, B 1, B 2 are disjoint. Then, Bii=1,2 forms a cyclical 4-edge-cut , by Lemma 2.3, GQll>=1 . Since G0=X0,Y0 is bipartite, it should be noted that each edge e i of E 0 is in these eight triangles and connects two vertices in Y 0; thus, the edges of EG-EB1-EB2 are X 0 Y 0 - edges and G - B 1 - B 2 has only quadrangles . Moreover, by Lemma 2.3, we can know G - B 1 - B 2 consists of l-2l>=2 layers of quadrangles (each layer is made up of four quadrangles). Thus, we have GH1 . Subcase 2.2: GE0 has exactly three components. Then, both of the two components of GE0 are K 2, and one component is K 1,2 . Without loss of generality, we suppose the component K 1,2 is induced by the edges e 3, e 4. Then, the two diamonds D 3, D 4 are adjacent, and D 1, D 2 are disjoint. Set C 1 = D 3 D 4 . Then, due to Lemma 2.3 and Lemma 3.1, C1 forms a cyclical 4-edge-cut, thus, GQ s , where Q s is the tubular {(3, 4), 4}-fullerene as shown in Figure 2, which means each of the two caps of Q s must contain two adjacent diamonds, contradicts that D 1, D 2 are disjoint. Subcase 2.3: GE0 has four components. Then, the four diagonal edges e 1, e 2, e 3, and e 4 are disjoint , that is, the four diamonds D 1, D 2, D 3, and D 4 cannot intersect at the diagonal edges. We have the four diamonds D 1, D 2, D 3, and D 4 as shown in Figure 7D. Then, GH2 . So far, we have completed the proof of Theorem 3.3. Inspired by Theorem 3.3, we immediately get the following theorems. FIGURE 5 GE0 has one component and the {(3,4),4}-fullerene Q 0 (A-F). FIGURE 6 GE0 has two components and the {(3,4),4}-fullerenes Qll>=1 (A-G). FIGURE 7 GE0 has three components (A,C) or four components (B,D). Theorem 3.4 Let G be a {(3, 4), 4}-fullerene, if GH1 , then akG=4 . Proof Let GH1 , that is, GQnn>=0 . By Theorem 3.2 and the definition of the anti-Kekule number, we only need to find an anti-Kekule set E 0 of G such that E0=4 . For convenience, let the plane embedding graph of Q n as shown in Figure 8. Q n consist of n + 1 concentric rings with four vertices on each ring and two vertices on two caps; these n + 1 concentric rings are recorded as R 1, R 2, R 3, ..., R n+1 from the inside to the outside. Next, the vertices of Q n are labeled as follows: the vertices shared by the four triangles on the two caps are represented by v', v '', respectively, and the vertices on Rii=1,2,3,...,n+1 are recorded as v i1, v i2, v i3, and v i4 (i = 1, 2, 3, ..., n + 1) in a clockwise direction such that v i1, v i3 (v i2,, and v i4) are on the same line . Next, we will prove Theorem 3.4 in two cases. Case 1: n is an odd number. Let E0=v'v11,v'v13,v''vn+1,2,v''vn+1,4 , and set G 1 = G - E 0. Then, E 0 is not a cyclically 4-edge-cut of G by Lemma 2.3. Moreover, E 0 is not a trivial 4-edge-cut as the four edges in E 0 are not incident with a common vertex. That is, G 1 is connected. Then, we prove that G 1 = G - E 0 has no perfect matching, and there are only quadrangular faces in G 1, so, G 1 is bipartite. We color the vertices of G 1 with black and white such that adjacent vertices in G 1 are assigned two distinct colors . Let M 0 denote the set of white vertices and N 0 denote the set of black vertices, then G1=G1M0,N0 , M0=2n+2 , N0=2n+4 . In accordance with Theorem 2.4, there exist M0VG1 such that oG1-M0=N0=2n+4>M0=2n+2 , so G 1 has no perfect matching. Case 2: n is an even number. Let E0=v'v11,v'v13,v''vn+1,1,v''vn+1,3 , and set G 2 = G - E 0. Also, G 2 is connected. There are only quadrangular faces in G 2; so, G 2 is also bipartite with one bipartition 2n + 2 vertices and the other bipartition 2n + 4 vertices, which means G 2 has no perfect matching. Therefore, we find the anti-Kekule set E 0 of G with E0=4 , which means akG=4 , if GH1 . Due to Theorem 3.4, if GH1 , then akG=4 . However, the anti-Kekule number of G can be 4 or 5 if GH2 . Next, we use a method to judge whether the anti-Kekule number of G can be 4 or 5 when GH2 . Before we give some definitions of G if GH2 . Let GH2 , the four diamonds of G be D 1, D 2, D 3, and D 4 and the four diagonal edges be e 1, e 2, e 3, and e 4 such that eiEDi , i = 1, 2, 3, 4. Set E0=e1,e2,e3,e4 and e 1 = v 1 v 2, e 2 = v 3 v 4, e 3 = v 5 v 6, and e 4 = v 7 v 8. The eight vertices of the four diagonal edges are called eight stars, and their union is denoted by V0=i=18vi . Set G 0 = G - E 0. Then, G 0 is bipartite, without loss of generality, we supposed the bipartitions of G0 were V 1, V 2. Then, by the proof of Theorem 3.3, we can know if akG=4 , then V 0 V 1 or V 0 V 2, which means akG=5 when V 0V 1 and V 0V 2. Thus, we have the following theorem. FIGURE 8 {(3,4),4}-Fullerenes Q n . FIGURE 9 Graph G - E 0; n is an odd number (A), and n is an even number (B). Theorem 3.5 Let G be a {(3, 4), 4}-fullerene, GH2 , if V 0 V 1 or V 0 V 2 , then akG=4 , otherwise, akG=5 . Proof By Theorem 3.2, we only need to show if V 0 V 1 or V 0 V 2, then akG=4 . Without loss of generality, suppose V 0 V 1. Then, GV1 consists of the four edges e 1, e 2, e 3, and e 4 and some singleton vertices. Since the four edges e 1, e 2, e 3, and e 4 cannot be incident with a common vertex, E 0 is not a trivial 4-edge-cut. However, E 0 also cannot be a cyclical 4-edge-cut by Lemma 2.3, as e i belongs to the intersection of two triangular faces for i = 1, 2, 3, 4. Thus, G 0 = G - E 0 is connected. On the other hand, by the degree-sum formula 4V2=4V1-8 , which means V1V2 . Thus, G 0 cannot have perfect matchings by Theorem 2.4. So, we find the anti-Kekule set E 0 with E0=4 . Immediately, we have akG=4 . Otherwise, by Theorem 3.2, akG=5 . By Theorem 3.5, for a {(3, 4), 4}-fullerene G with GH2 , we can give the method to judge the anti-Kekule number of graph G is 4 or 5 as follows: Step 1: Delete the four diagonal edges e 1, e 2, e 3, and e 4. Step 2: Color the vertices of G0=G-e1,e2,e3,e4 with black and white. Step 3: If we find the eight stars are in the same color, then akG=4 , otherwise, akG=5 . 4 Conclusion In this paper, we have obtained the scope of the anti-Kekule number of {(3, 4), 4}-fullerenes in Theorem 3.2; at the same time, we characterized {(3, 4), 4}-fullerenes with anti-Kekule number 4 in Theorem 3.3, which includes two kinds of graphs H1,H2 . As a consequence, we proved that if GH1 , then akG=4 . Interestingly, by the proof of Theorem 3.3, we found the {(3, 4), 4}-fullerene G belongs to H2 , but the anti-Kekule number of G is not always 4; therefore, at the end of this paper, we gave a condition for judging whether the anti-Kekule number of graph G is 4 or 5. Data availability statement The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author. Author contributions RY performed the ideas and the formulation of overarching research goals and aims. HJ wrote the first manuscript draft and performed the review and revision of the first draft. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Deza M. Sikiric M. (2012). 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PMC10000291 | Front Psychol Front Psychol Front. Psychol. Frontiers in Psychology 1664-1078 Frontiers Media S.A. 10.3389/fpsyg.2023.1087979 Psychology Original Research Cross-cultural study of kinship premium and social discounting of generosity Liu Jiawei 1 2 3 4 + Derrington Edmund 3 4 + Benistant Julien 3 4 Corgnet Brice 5 Van der Henst Jean-Baptiste 3 4 Tang Zixuan 1 2 3 4 Qu Chen 1 2 3 * ++ Dreher Jean-Claude 3 4 * ++ 1Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou, China 2Guangdong Key Laboratory of Mental Health and Cognitive Science, School of Psychology, Center for Studies of Psychological Application, South China Normal University, Guangzhou, China 3Laboratory of Neuroeconomics, Institut des Sciences Cognitives Marc Jeannerod, CNRS, Lyon, France 4UFR Biosciences, Universite Claude Bernard Lyon 1, Lyon, France 5EmLyon, Ecully, France Edited by: Yung-Jong Shiah, National Kaohsiung Normal University, Taiwan Reviewed by: Nan Zhu, University of Macau, China; Yuqing Zhou, Julius Maximilian University of Wurzburg, Germany *Correspondence: Jean-Claude Dreher, [email protected] Chen Qu, [email protected] +These authors share first authorship ++These authors have contributed equally to this work and share last authorship This article was submitted to Cultural Psychology, a section of the journal Frontiers in Psychology 24 2 2023 2023 14 108797902 11 2022 23 1 2023 Copyright (c) 2023 Liu, Derrington, Benistant, Corgnet, Van der Henst, Tang, Qu and Dreher. 2023 Liu, Derrington, Benistant, Corgnet, Van der Henst, Tang, Qu and Dreher This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Social discounting predicts that one's concern for others decreases with increasing social distance. Cultural dimensions may influence this social behavior. Here, we used a dictator game, in which the participants and real members of their social entourage profited from the partition of the endowments determined by the participant, to compare how Chinese and French university students shared endowments with people at different social distances. We tested two hypotheses based on the concepts of kinship premium and cultural collectivism. Stronger ties between close family members were expected among Chinese. This may predict a larger "kinship premium," i.e., increased generosity to family members at close social distances, in Chinese relative to French participants. Similarly, because collectivism is thought to be stronger in Asian than western societies, greater generosity at larger social distances might also be expected among Chinese participants. The results showed that Chinese were more generous than French at close social distances but discounted more as social distance increased. This difference between French and Chinese was confined to family members and no significant difference in generosity was observed between French and Chinese for non-family members at any social distance. Our findings evidence a stronger kinship premium among Chinese than French students, and no significant effect of cultural collectivism. social discounting kinship premium altruism cultural collectivism Chinese generosity Agence Nationale de la Recherche 10.13039/501100001665 ANR-11-LABEX-0042 ANR-11-IDEX-0007 National Social Science Fund of China 10.13039/501100012456 JL was funded by the China Scholarship Council (Grant No. 201808070050) for their financial support for her doctoral studies. This research has benefited from the financial support of IDEXLYON from Universite de Lyon (project INDEPTH) within the Programme Investissements d'Avenir (ANR-16-IDEX-0005) and of the LABEX CORTEX (ANR-11-LABEX-0042) of Universite de Lyon, within the program Investissements d'Avenir (ANR-11-IDEX-007) operated by the French National Research Agency, and the Program for National Science Foundation of China (31970982). pmc1. Introduction Altruism, generosity at one's own expense, is an important component of human prosocial behavior. However, individuals are not equally generous to everyone and tend to favor family and people with whom they have close personal relationships. Social discounting is based on the concept of temporal discounting, a well characterized phenomenon by which a reward progressively loses subjective value with the delay that is imposed prior to the reward's arrival (Rachlin et al., 1991). In either real or hypothetical experiments, participants have been asked to choose how to allocate money or other resources, between themselves and potential recipients at different social distances. The amount donated usually falls with increasing social distance between the two parties (Wu et al., 2011; Strang et al., 2017). Thus, the subjective value of being more generous is discounted as social distance increases. One of the most studied inter-cultural dimensions is the degree of Collectivism/Individualism (Hofstede, 1980b,1984; Triandis, 1989). Collectivism is a characteristic of cultures in which people perceive themselves to be integrated and interdependent, whereas in individualistic societies, people are more focused on their own wellbeing, and that of closely related others such as immediate family (Hofstede, 1980a, p. 45; Hofstede, 1984; Markus and Kitayama, 1991; Kitayama and Uskul, 2011). One might thus expect different patterns of social discounting in participants who conform to collectivist as opposed to individualist cultural identities. Cross-cultural variations in social discounting might even provide an objective measure for the degree of social integration of individuals with other members of their society. Generosity to genetically related others, such as close family members, has also been distinguished from generosity to friends or other unrelated individuals (Darlington, 1978). Indeed, more recently, studies have shown that kinship creates a specific unique contribution to generosity over and above the effects of emotional closeness such that participants in experiments are more generous to kin than might be expected if generosity depended on emotional closeness alone. This has been defined as "kinship premium" (Curry et al., 2013; Pollet et al., 2013; Booysen et al., 2018a). Social discounting has also evidenced such kinship premiums (Rachlin and Jones, 2008; Booysen et al., 2018a). Collectivism or social interdependence is thought to be stronger in Asian than in western societies (Leung and Iwawaki, 1988; Hui et al., 1991; Oyserman et al., 2002). Previous cross cultural studies have compared social discounting in Japanese and German students (Ishii and Eisen, 2018), Chinese and German students (Strombach et al., 2014) and Japanese and American students (Ito et al., 2011; Romanowich and Igaki, 2017; Stegall et al., 2019). Two studies found that western participants were more generous at close social distances but discounted more rapidly as social distance increased, and this was taken as evidence that the greater social cohesiveness of Asian societies was reflected by lower levels of social discounting (Strombach et al., 2014; Ishii and Eisen, 2018). However, two studies reported no significant differences between Asian and Western participants (Romanowich and Igaki, 2017; Stegall et al., 2019) or Americans and Germans (Stegall et al., 2019), and one found that Asian participants (Japanese), discounted more rapidly than American college students as social distance increased (Ito et al., 2011). These mixed findings indicate that more research is needed to understand the influence of cultural differences on social discounting, and, no study analyzed whether social discounting was affected by cross-cultural differences in kinship premiums. Most cross-cultural studies used abstract games to study social discounting. All were based on binary decision tasks that measure participants' preference for a generous or a more selfish option, to divide money or other resources between themselves and another at a given social distance. This forced choice may influence the decisions made by the participants. Indeed, neither of the options offered on a given trial may reflect the true preference of the participants. Furthermore, calculation of the participants' generosity at a given social distance can be complicated because an accurate estimation of a participant's generosity depends on the participant behaving consistently across all the trials at each social distance. This is frequently not the case (Booysen et al., 2018b). Finally, many of the previous studies are completely or partially hypothetical, with the participants' decisions having no concrete consequences for themselves and/or the hypothetical "recipients." We took a new approach to study social integration and kinship premium by analyzing social discounting with a concrete dictator game. Participants chose freely how to divide endowments, that varied in size on different trials, with recipients at different social distances. These recipients were not hypothetical, participants identified them from their own social entourage. Only at high social distances were potential beneficiaries anonymous. At the end of the experiment a single trial was chosen at random and its consequences applied to both the participant and the recipient. Thus, both participants and recipients would enjoy the fruits of the participants' avarice or largesse. This non-deceptive and non-hypothetical approach allowed us to mitigate concerns that have been raised concerning hypothetical biases that occur in similar economic games (Forsythe et al., 1994; Ben-Ner et al., 2008; Buhren and Kundt, 2015). Furthermore, participants were absolutely free to choose how much to donate, without any external cues as to what might constitute a generous or selfish allocation. Finally, we used participants from two countries, France and China, known to exhibit different levels of Individualism/Collectivism. This rigorous behavioral economics approach allowed us to study first whether social discounting differs between groups with different levels of Collectivism and second to compare kinship premiums in university students from the two countries. 2. Materials and methods 2.1. Participants A total of 102 subjects participated in our experiment. Testing was carried out in 2 laboratories: South China Normal University (Guangzhou, China) and Institute of Cognitive Science (Lyon, France). A total of 51 Chinese participants (26 females; M age = 20.45, SD = 1.36) were students recruited at the SCNl University and 51 French participants (25 females; M age = 21.24, SD = 2.14) were students recruited from the Lyon 1 University. The sample size was based on a reference study in the domain which tested around 50 participants per group (Strombach et al., 2014). All participants were psychiatrically and neurologically healthy and indicated they were not taking any medication. The two studies were approved by the local ethics committees. All experimental protocols and procedures were conducted in accordance with institutional review-board guidelines for experimental testing and complied with the latest revision of the Declaration of Helsinki. Participants gave written consent for participation in the study and were free to leave at any time. 2.2. Experimental design Subjects were required to perform a self-representation task in which they rated their level of intimacy with a list of relationships on a 100-point scale: mother, father, siblings, grandparents, kin, best friend, roommate, colleagues, neighbors, acquaintances, partner, strangers and friend circle. When subjects had no equivalent social relationship (e.g., partner) they skipped that question. Subjects then performed the social discounting task, which was a dictator game repeated over 40 trials in a random order in which subjects chose how to split an endowment between themselves and identified recipients at different social distances. First, the subjects were required to identify the recipients from their own social entourage that best corresponded to each social distance (1, 2, 3, 5, 10, 20, 50, and 100), and indicate the relationship between them (i.e., Social Distance 1, name: Mary March, relationship: Mother). Participants were informed that a random trial would be selected, in which the receiver was sent 10% of the amount indicated by the participant for that trial. Importantly, because by definition the receivers at social distances 50 and 100 corresponded to someone that participants did not know, the money for the trials corresponding to these social distances would be sent to a charity project (online payment platform). We also varied the size of the endowment within subjects with five different endowment sizes at each social distance (EUR80, EUR90, EUR100, EUR110, and EUR120, or the same amount in Yuan for Chinese subjects). This allowed as to calculate mean values for generosity at each social distance for each participant and to determine whether the endowment size altered their generosity. In each trial, social distance was represented on a scale of 101 small icons displayed at the top of the screen. The subject was indicated by a white icon at the left extremity, and the receiver by a blue icon labeled with a number, the smaller the number, the closer the social distance . Unlike previous studies, which used forced choices, in our study generosity could be measured directly as the proportion of the endowment that the participants chose freely to donate. The amount of the endowment for the trial was displayed on the screen, and the participant indicated how much was given to the recipient. This amount could not exceed the endowment. Finally, at the end of the trial the participant was reminded how the money had been allocated. FIGURE 1 Experimental design. After a fixation cross, a social distance line was displayed across the top of the screen showing a white and a blue person, respectively, representing the participant and the receiver. The number above the blue icon indicated their exact social distance to the participant. Then, participants were shown one of 5 possible endowments (EUR80, EUR90, EUR100, EUR110, EUR120 for French, or the same amount in Yuan for Chinese subjects). Participants had to type on a keyboard the exact amount that they were willing to send to the recipient (here EUR10). A feedback screen indicated the amounts for the participant (here EUR80), and the receiver (here EUR10). Participants received a fixed amount of EUR 6 in France and 10 Yuan in China. These amounts were selected because in July 2016 (when the experiments took place), the French purchasing power was about 1.6 times that in China. In addition, the participant received their share of the allocation from the randomly selected trial paid at 10% of its full value. Participants transferred the money directly to their recipients under the supervision of experimenters by bank accounts (French), and by the payment application of Alipay or Wechat (Chinese). Once the 40 trials elapsed, participants completed the shortened version of the Individualism-Collectivism (IND-COL) scale composed of 33 items on a 6-point scale to test for between and within culture variations (Hui and Yee, 1994). This scale allows participants to be scored with respect to five primary categories of Individualism and Collectivism: "Kin and neighbors/susceptibility to influence (KN)," measures the extent to which participants are influenced by family and neighbors as opposed to having a more independent attitude, "Neighbor/social isolation (NE)," measures the extent of social interaction and casual relationships with their neighbors, "Colleagues and friends/supportive exchanges (CF)": measures the degree of interdependence of participants with coworkers and friends, "Parents and spouse/distinctiveness of personal identity (PS)," measures the participants' individualism within their nuclear family, and, "Parents/consultation and sharing (PA)": measures the extent to which participants are influenced by and interact with their parents. Two second order factors, "Ingroup Solidarity" (calculated from the sums of the CF, PA, and PS subscales) and "Social Obligation" (calculated from the sum of the KN and NE subscales) and a global IND-COL score (the sum of all five subscales) are calculated from these scores. Finally, participants were asked to what extent they identified with their own culture on a scale from 1 to 5. The task was programmed using E-prime 2.0 and all the instructions were delivered in the subjects' native language. The detailed instructions, can be found in the Supplementary material section. 2.3. Model estimation To analyze social discounting we fitted the following discounting functions: the Constant Sensitivity model [Ebert and Prelec, 2007; Eq. (1)], Beta-Delta model [Laibson, 1997; Eq. (2)] and the Hyperbolic model [Jones and Rachlin, 2006, 2009; Eq. (3)]. One of our central hypotheses was that individuals with different levels of collectivism/individualism may show different patterns of social discounting that may be best accounted for by different models, or by the same model but with different values of the pertinent variables for that model. (1) v=e[-(a*D)b] (2) v=b*dD (3) v=V1+kD In all the equations v indicates the subjective value to the participant of being generous to the recipient and D symbolizes the social distance. Respectively, Eq. (1), the Constant Sensitivity model: a sets the distance to a theoretical boundary that separates close from distant relationships, and b represents the degree of sensitivity to social distance. For smaller values of b there is less sensitivity to social distance, which indicates that the participant discriminates less between recipients at closer and recipients at more distant social distances. Eq. (2), the Beta-Delta model: b represents the extra value awarded to the closest social distance value and d captures a constant rate of social discounting, that is, ddetermines the rate at which generosity decreases as social distance increases, in the standard exponential model. When d is higher the participants will discriminate proportionally more between recipients at closer and more distant social distances Eq. (3), the Hyperbolic model: k represents a constant that measures the degree of social discounting, i.e., the extent to which generosity decreases at each social distance compared to V, which is the theoretical undiscounted value of generosity at distance D = 0. Higher values of k will result in the participants discriminating proportionally more between recipients at closer and recipients at greater social distances. We fitted the models to the individual social discounting curves of each participant. The curves were generated from the mean proportions of each of the five endowments allocated by each participant, at each social distance. Use of the mean percentage of the amount given by each participant, as opposed to the median was justified by the fact that our participants made free choices, as opposed to forced choices between a series of more or less generous offers at each social distance (Rachlin and Jones, 2008; Strombach et al., 2014). The non-linear least-squares estimation, nlmrt package (Nash, 2012) in R was used to calculate the Akaike Information Criterion (AIC) for how well each individual fit each model, and the sum of AIC for all individuals fitting that model was used to calculate the group AIC. Since the overwhelming majority of AIC were negative (98.5%), the sum of the AIC for all the subjects fitting that model reflects the goodness of fit of the whole group of curves, one for each participant, to each model. The model with the lowest Group AIC was that which best reflects the group as a whole. The mean Individual AIC reflects how well each individual in the Group fits each model. Results from the model estimation show that one Chinese and one French participant did not fit the Hyperbolic model. 2.4. Regression analysis To address how specific factors (e.g., Culture, family relationships, subscales of IND-COL scale etc.) affected generosity across social distance, we conducted 6 separate generalized linear models (GLMs) with the proportion of the endowment given as a dependent variable. We use GLMs with a logit link function and a binomial family to account for the specificity of the dependent variable, we also clustered the standard error at the participant level. Specifically, we ran 3 GLMs at social distances 1~100 (GLMs 1, 2, and 3), and 3 GLMs for social distances 1~20 (for GLMs 4, 5, and 6), using the glm function from STATA. We included in all GLMs the following independent variables: whether the participant was French or Chinese (variable French, Chinese = 0, French = 1), the social distance (8 level values for GLMs 1, 2, and 3: 1, 2, 3, 5, 10, 20, 50, and 100; and 6 values for GLMs 4, 5, and 6: 1, 2, 3, 5, 10, and 20), the endowment size (EUR80, EUR90, EUR100, EUR110, EUR120), whether the recipient was a family member or not (variable Family member). In GLMs 2 and 5, we also included interactions between the variable Family member, Distance and French. In addition to these interactions, we also included the five subscales of the IND-COL as variables in GLMs 3 and 6. To identify correlations between social discounting and the participants' scores on the IND-COL scales, linear regressions were performed between the participants' IND-COL scores on each of the five subscales, the 2 s order factors (Ingroup solidarity and Social Obligation) and their global IND-COL score with their individual scores for the parameters in the three models (a and b for the Constant Sensitivity model, b and th for the Beta-Delta model and V and k for the hyperbolic model) in R. 3. Results 3.1. Cultural comparison of French and Chinese participants Participants rated their level of identification with their respective culture on a five-point Likert scale. Chinese participants felt significantly more connected to their culture than the French, (Mann-Witney U-test; M Chinese = 4.08, SD Chinese = 0.72; M French = 3.67, SD French = 0.91; z = 2.58, p = 0.01, U = 1648). This closer association was similar to that reported previously when Chinese were compared to Germans (Strombach et al., 2014). For the Self-Representation task, the Chinese self-rated their closeness to progenitors (mother, father, grandparents) and groups of people in society (neighbors, circle of friends, acquaintances, or strangers) significantly closer than the French (unpaired t-test, p < 0.05) (Table 1). However, Chinese and French participants were not different in their ratings of closeness to their peers (siblings, best friend, roommates, colleagues or partner). Globally these results show a tendency for French participants to consider themselves to be more socially distant than the Chinese from family authority figures (parents and grandparents), and also groups of people in society (circle of friends, neighbors, strangers). This is broadly in agreement with similar experiments comparing Chinese and German students (Strombach et al., 2014). However, unlike German students, the French students in our study also considered themselves as more socially distant from strangers, their circle of friends, their neighbors and indeed their acquaintances than the Chinese. TABLE 1 Mean perceived social distance in the self-representation task. Relationship Chinese French t df p Mother 5.54 (9.39) 10.29 (10.52) -2.397 98.14 0.018* Father 6.53 (9.15) 20.08 (24.98) -3.637 63.191 0.001** Brother and sister 9.22 (11.08) 11.88 (13.24) -1.097 96.629 0.275 Grandparents 14.80 (14.96) 26.75 (21.59) -3.228 89.253 0.002** Kinships 29.39 (21.59) 29.59 (18.96) -0.049 98.359 0.961 Best friend 12.06 (10.32) 13.37 (13.31) -0.557 94.144 0.579 Roommates 24.86 (16.95) 29.55 (22.15) -1.2 93.615 0.233 Classmates 38.73 (21.32) 41.94 (22.26) -0.745 99.817 0.458 Neighbors 47.29 (24.48) 71.41 (22.32) -5.2 99.156 0.000*** Acquaintances 36.49 (21.49) 60.35 (21.60) -5.593 99.997 0.000*** Partner 13.22 (19.11) 7.51 14.66) 1.274 34.166 0.211 Strangers 81.68 (19.75) 98.20 (5.54) -5.697 56.529 0.000*** Circle of friends 47.98 (25.98) 72.00 (17.86) -5.405 86.683 0.000*** The mean social distance to different types of social relations as estimated by the participants in the self-representation task. Standard errors are in parentheses. The significance of differences was determined by an unpaired student's t-test. *p < 0.05, **p < 0.01, ***p < 0.001. The shortened version of the Individualism-Collectivism scale (Hui and Yee, 1994), in which higher scores indicate more collectivist tendencies, also highlighted cultural differences (Table 2). Although there was no significant difference between the global IND-COL scores of the French and Chinese participants (M Chinese = 12.82, SD Chinese = 13.04; M French = 9.35, SD French = 12.12), Chinese participants scored significantly higher in two individual subscales, among five that represent how individuals relate to relationships. Specifically, the Chinese scored significantly higher than the French in the "Kin and neighbors/susceptibility to influence" (M Chinese = 1.10, SD Chinese = 5.58; M French = -0.94, SD French = 3.54; t = 2.204, p = 0.03) and the "Neighbor/social isolation" factors (M Chinese = -12.39, SD Chinese = 5.10; M French = -15.90, SD French = 5.14; t = 3.463, p < 0.001). For the three other individual subscales scores were not significantly different between the two pools of participants (Table 2). With regard to the higher order factors, Ingroup Solidarity, provides a measure of the participants collectivism with regard to the nuclear family and close friends, whereas, Social Obligation measures integration and collectivism with respect to society as a whole (Hui and Yee, 1994). There was no significant difference between the French and the Chinese students with respect to the former, however, for the latter the Chinese participants scored significantly higher (M Chinese = -11.29, SD Chinese = 7.91; M French = -16.84, SD French = 6.44; t = 3.885, p < 0.001), indicating a higher degree of collectivism with society as a whole. TABLE 2 Results of individualism-collectivism scale IND-COL scales and subscales (Hui and Yee, 1994). Scale Chinese French t df p CF 21.67 (5.25) 22.45 (4.01) -0.848 93.502 0.398 PA 2.29 (2.68) 1.98 (2.79) 0.579 99.835 0.564 PS 0.37 (3.58) 1.76 (5.41) -1.533 86.825 0.129 KN 1.10 (5.58) -0.94 (3.54) 2.204 84.54 0.03* NE -12.39 (5.10) -15.90 (5.14) 3.463 99.993 0.001*** In group solidarity 24.12 (8.97) 26.20 (8.16) -1.224 99.12 0.224 Social obligation -11.29 (7.91) -16.84 (6.44) 3.885 96.031 0*** Global 12.82 (13.43) 9.35 (12.12) 1.37 98.972 0.174 Mean results of the IND-COL test for the Chinese and French students. Standard errors are in parentheses. The significance of differences was determined by an unpaired student's t-test. *p < 0.05, ***p < 0.001. CF, PA, PS, KN, and NE stand for subscales colleagues and friends/supportive exchanges, parents/consultation and sharing, parents and spouse/distinctiveness of personal identity, Kin and neighbors/susceptibility to influence, and neighbor/social isolation, respectively. Higher scores indicate a greater degree of collectivism. These results reinforce the picture that the Chinese students feel generally more integrated with their society as a whole than the French, however, differences with respect to close family and friends are less consistent. The French family relationships and in particular parents were scored as being significantly more distant than the Chinese on the self-representation task, but were not significantly different to the Chinese on the associated IND-COL subscales or with respect to Ingroup Solidarity. 3.2. Comparison of French and Chinese recipients at different social distances Participants were required to choose recipients from their own social entourage (family and friends etc.) that best corresponded to the social distances 1, 2, 3, 5, 10, and 20, in which 1 corresponds to the closest person to them and 100 corresponds to a perfect stranger. The recipients at distance 50 and 100 were anonymous since the former would correspond to a person they occasionally encounter, but do not know, and the latter to a person they do not know at all. We compared the types of relationship between Chinese and French participants and their choices for recipients at social distances 1 to 20. Both the French and the Chinese identified similarly high proportions of family members (Mother, Father, Brother or Sister, Grandparents, other blood relatives, and Partner) at social distances 1 (>90%), 2 (>70%), 3 (>50%) and 5 (>40%) . However, at social distances 10 and 20 about 40% of French participants continued to include blood relatives whereas significantly fewer Chinese participants, (about 20%), did so (social distance 10: (N Chinese = 10, N French = 23; kh2 = 6.451, df = 1, p = 0.011); and social distance 20: (N Chinese = 11, N French = 27; kh2 = 8.137, df = 1, p = 0.004). FIGURE 2 Inclusion of family at the social distance range 1~20. Less participants choose family members as recipients at greater social distances, this decline was more rapid for the Chinese than for the French. *p < 0.05, **p < 0.01, ***p < 0.001. For each social distance, we compared the proportion of the endowments donated across Groups (Table 3). As expected, generosity decreased as social distance increased. We observed a significant difference in the allocation of the endowment by the French and the Chinese at social distance 1, (M Chinese = 0.843, SD = 0.198; M French = 0.672, SD = 0.217, t = 4.15, p < 0.001); social distance 2, (M Chinese = 0.703, SD = 0.227; M French = 0.573, SD = 0.240, t = 2.81, p < 0.01); and social distance 3 (M Chinese = 0.165, SD = 0.131; M French = 0.114, SD = 0.153, t = 2.00, p < 0.05). However, at greater social distances there was no significant difference between the proportions of the endowments donated by the French and the Chinese. TABLE 3 Proportion of the endowments allocated to recipients at each social distance. Social distance Chinese mean (SD) French mean (SD) t df p 1 0.84 (0.20) 0.67 (0.22) 4.147 99.211 0.000*** 2 0.70 (0.23) 0.57 (0.24) 2.805 99.688 0.006** 3 0.66 (0.26) 0.56 (0.25) 2.001 99.978 0.048* 5 0.56 (0.27) 0.47 (0.20) 1.764 92.056 0.081 10 0.43 (0.24) 0.43 (0.21) -0.036 97.477 0.971 20 0.36 (0.22) 0.36 (0.19) 0.097 98.502 0.923 50 0.17 (0.13) 0.11 (0.15) 1.831 97.719 0.070 100 0.07 (0.08) 0.08 (0.15) -0.453 77.43 0.652 Standard errors are in parentheses; *p < 0.05, **p < 0.01, ***p < 0.001. 3.3. Model-based results To determine how social distance affects generosity, we compared the group giving behavior of Chinese and French with 3 different models (the Hyperbolic model, the Beta-delta model, and the Constant Sensitivity model). The major difference between the three models concerns the predicted evolution of discounting behavior as social distance increases. All the models predict that generosity will decline as social distance increases. For the hyperbolic model and the Beta-Delta model the difference in generosity per unit of social distance should decline as social distance increases according to hyperbolic and exponential curves, respectively. Similarly, for the Constant Sensitivity model when b < 1 the generosity per unit of social distance declines exponentially as social distance increases. However, when b > 1 and social distance <1/a, generosity declines less rapidly per unit of social distance. The best model to account for the data of Chinese participants was the Constant Sensitivity model . Both the Hyperbolic model (mean AIC Hyperbolic Chinese = -61.28) and the Beta Delta model (mean AIC Beta/Delta Chinese = -59.79) were significantly worse at explaining their behavior. The best model to account for the data of the French participants was the Beta-Delta model (mean AIC Beta/Delta French = -67.53). At the individual level this was only just better than the Constant Sensitivity model (AIC Constant Sensitivity French = -65.48) and the Hyperbolic model (AIC Hyperbolic French = -65.28), however, the above are the mean differences in AIC for each individual in the group. The Group differences in AIC are 51-fold higher (N = 51), indicating that the best models to account for the data of each group is much better than the second or third best models. Thus, although there is some justification for comparing the two groups with respect to the parameters a and b of the Constant Sensitivity model, which fits the French at least as well as it fits the Chinese, and is globally the best model for the two groups combined (Table 5), comparisons for the parameters of the Beta Delta model or the Hyperbolic model are rather more tenuous. TABLE 4 Model selection according to AIC. Model Formula Individual AIC (mean) Group AIC Chinese French Chinese French Constant sensitivity v = e[-(a*D)b] -64.95 -65.48 -3208 -3339 Beta-delta v = b*dD -59.79 -67.53 -3049 -3444 Hyperbolic v=V1+kD -61.28 -65.28 -3063 -3263 Mean individual AIC (for all participants). The group AIC is the sum of all the AIC for all group members that fit the model. One Chinese participant did not fit the Constant Sensitivity model. Another Chinese participant and one French student did not fit the Hyperbolic model. Since the vast majority of AIC values (over 97%) were negative, the non-inclusion of a group member who did not fit that model tended to penalize the group AIC of that model. Globally, all the models tended to fit the French better than the Chinese. The Constant Sensitivity model was the best model for all participants and by far the best model for the Chinese, however, the beta-delta model was the best model for the French, but the worst model for the Chinese. FIGURE 3 Social discounting behavior of Chinese and French participants in the Constant Sensitivity model. The graph shows the proportions of endowments offered by the participants to recipients at each social distance, as estimated by the Constant Sensitivity model, which was globally the best model to account for social discounting for all participants and for the Chinese participants in particular. Although it was not the best model of the French students' discounting behavior, it fit them similarly well as the Chinese. TABLE 5 Comparison of the parameters for each social discounting model. Constant sensitivity Beta delta Hyperbolic model a b b d V k Chinese Mean 0.187 0.932 0.948 0.893 1.528 0.740 1.823 SD 0.473 0.814 0.352 0.141 1.851 French Mean 0.313 0.525 0.666 0.950 0.771 0.151 0.277 SD 0.693 0.426 0.241 0.052 0.336 P (Mann-Whitney U-test) 0.057 <0.001 <0.001 0.062 <0.001 0.168 Means and standard deviations for the two parameters for each of the social discounting models. Mann-Whitney U-tests showed the parameter b of the constant sensitivity was significantly greater for the Chinese than the French indicating a greater sensitivity to social distance, meaning that the level of generosity of the Chinese participants falls more quickly than that of the French as social distance increases. The significantly higher levels of b in the beta-delta model suggest that Chinese have greater "added value" for recipients at the closest social distances than the French, however, this must be treated with caution because this was the worst model for the Chinese. Similarly, according to the Hyperbolic model the Chinese participants show a greater level of generosity to a theoretical recipient at social distance zero, however, this was the worst model for the French. The parameter a, which in our experiment delimits the border between "close" and "distant" social relations, (defined as 1/a), was not significantly different between French and Chinese participants (M Chinese = 0.187, M French = 0.313; U = 995, Z = 1.902, p = 0.057). This indicates that the social distances at which the French and Chinese participants discriminate close from distant relationships with respect to their generosity are not significantly different. However, the parameter b of the Constant Sensitivity model differed significantly between the Chinese and French (Mann-Whitney U-test; M Chinese = 0.932, M French = 0.525; U = 1848, Z = 3.892, p < 0.001), indicating that the Chinese show significantly greater sensitivity to social distance. This also suggests that for a significant number of Chinese participants b > 1. When this is the case social discounting occurs more slowly at very low social distances and then increases according to an exponential decay at the frontier between close and distant social distances as determined by the parameter a. 3.4. Regression analysis of factors affecting social discounting To understand which factors shaped the social discounting curves of the French and Chinese participants we used General Linear Models (GLMs) to analyze the data. We conducted three GLMs for distributed differences between French and Chinese participants at social distances 1~100. We tested whether the proportion of endowment donated by each participant was affected by the group (variable Nationality, with the French equals 1, and the Chinese equals 0), by endowment size (variable Endowment), social distance between the participant and the recipient (variable Distance), whether the recipient was a family member or not (variable Family member, equals 1 when the recipient was a family member and 0 otherwise). We ran three logit transformed GLMs and reported the marginal effects . We varied whether we included interactions between the variable Nationality, Distance and Family member (GLM2) and whether we included the 5 components of the IND-COL scale (GLM3). FIGURE 4 Interaction effect between group family relations and social distance on generosity at social distances 1~100. The solid lines show the proportion of the endowments offered by participants to family members, for the French (left graph, blue), and the Chinese (right graph, red) as estimated by GLM3. The dotted lines represent the proportions of the endowments offered to non-family members. The solid triangles show the mean proportions of the endowments offered to family members for the Chinese and French. The hollow dots show the mean proportions offered to non-family members. At social distances 50 and 100 the participants did not know the recipients, who could not be family members. TABLE 6 Generalized linear models predicting social discounting behavior. GLM 1 GLM 2 GLM 3 GLM 4 GLM 5 GLM 6 Parameters Marginal effects (standard errors) French -0.077 (0.300)** -0.067 (0.300)** -0.087 (0.032)*** -0.093 (0.036)** -0.084 (0.036)** -0.105 (0.040)** Endowment <0.001 (<0.001)*** <0.001 (< 0.001)*** <0.001 (< 0.001)*** <0.001 (0.001)*** <0.001 (<0.001)*** <0.001 (< 0.001)*** Distance -0.006 (< 0.001)*** -0.011 (< 0.001)*** -0.011 (< 0.001)*** -0.015 (0.001)*** -0.015 (0.001)*** -0.015 (0.001)*** Family member 0.126 (0.176)*** 0.077 (0.016)*** 0.075 (0.015)*** 0.122 (0.020)*** 0.119 (0.020)*** 0.114 (0.020)*** French x distance 0.003 (0.001)* 0.003 (0.001)* 0.004 (0.002)* 0.004 (0.002)* French x family member -0.060 (0.032) -0.039 (0.033) -0.098 (0.041)* -0.072 (0.042)* Family member x distance -0.008 (0.001)*** -0.008 (0.001)*** -0.008 (0.002)*** -0.007 (0.002)** French x family member x distance: Family member: French x distance 0.007 (< 0.001)* 0.007 (0.003)* 0.007 (0.003)* 0.007 (0.003)* Non-family member: French x distance <0.001 (< 0.001) <0.001 (< 0.001) <0.001 (< 0.001) 0.001 (0.003) CF 0.001 (0.003) 0.001 (0.005) PA <0.001 (<0.001) 0.001 (0.006) PS 0.001 (0.003) 0.001 (0.004) KN -0.003 (< 0.001) -0.003 (0.005) NE -0.003 (0.003) -0.004 (0.003) Number of observations 4080 4080 4000 3060 3060 3000 AIC 0.867 0.854 0.855 0.966 0.956 0.960 Marginal effects are shown in bold type, standard errors clustered at the participants' level are in parentheses; *p < 0.05, **p < 0.01, ***p < 0.001. We included in all GLMs the following independent variables: whether the participant was French or Chinese (variable French, Chinese = 0, French = 1), the social distance (8 level values for GLMs 1, 2 and 3:, 1, 2, 3, 5, 10, 20, 50, and 100; and 6 values for GLMs 4, 5, and 6: 1, 2, 3, 5, 10, and 20), the endowment size (EUR80, EUR90, EUR100, EUR110, EUR120), whether the recipient was a family member or not (variable family member). GLMs 1-3 were computed using the data over social distances 1-100, while GLMs 4-6 were computed only from social distances 1-20, in order make a more accurate comparison of how the Chinese and French might differ in their treatment of family members with non-family members at the same social distances. Standard errors clustered at the participant level are in parentheses. IND-COL results were not available for two subjects who therefore were excluded from GLM3 and GLM6, which accounts for the differences in the number of observations and p-values for GLM 3 compared to GLM1 and GLM2 and for GLM6 compared to GLM4 and GLM5. The BOLD type indicated the within-factors. Results showed that the French were overall less generous than Chinese participants (GLM1, Nationality), that participants were more generous with larger endowments (GLM1, Endowment), that generosity decreased with increasing social distance, (GLM1, Distance) and, that participants were more generous to family members than other recipients (GLM1, Family member). This last finding indicates that both the French and Chinese family members profited from a kinship premium. Concerning the interactions reported in model GLM 2, we found that Chinese participants were more sensitive to social distance, discounting more than the French as social distance increased (GLM 2, Nationality x Distance). However, the Chinese were only marginally more generous to family members than non-family members than the French. The significance of this difference did not achieve the standard threshold of 0.05 (GLM 2, Nationality x Family member: p = 0.058). Social discounting was also stronger, i.e., there was a greater sensitivity to social distance for family members than non-family members, indicating that the kinship premium is severely discounted as social distance increases. We found that Chinese participants were more sensitive than the French to social distance, which was driven primarily by their treatment of family members, because this difference did not hold for non-family members (GLM2 Family member: Nationality x Distance and Non-family member: Nationality x Distance). This was further supported by the finding that the triple interaction Nationality x Family member x Distance revealed a significant difference between the French and the Chinese concerning social discounting for family members with respect to non-family members. Thus, the Chinese were significantly more sensitive than the French to the social distance of family members compared to non-family members (GLM 2). Finally, the inclusion of the five components of the IND-COL scale (GLM 3), had no significant effect on the results. This suggests that these factors do not account for any significant amount of the variance of social discounting in our participants. The better to discriminate possible marginal effects of kinship premium or IND-COL scale factors we ran GLM 4, GLM 5 and GLM 6 which were identical to GLM 1, GLM 2, and GLM 3. However, we removed the data for social distances 50 and 100. This was justified because in our experiments, family members could not be included at social distances 50 and 100. Therefore, the inclusion of the data at these social distances obscures differences in the treatment of family and non-family members (Table 6). Indeed, when this analysis was carried out a significant interaction between Nationality x Family was revealed. Thus, over the social distances at which generosity to family members can be compared with the generosity to non-family members (Social Distances 1~20) the Chinese showed a significantly greater generosity to family than to non-family members than the French (GLM 5). This can be appreciated from the difference between the gradients of social discounting for family as opposed to non-family members for the French and the Chinese as social distance increases . This was the only difference observed between GLMs 1, 2, and 3 and GLMs 4, 5, and 6. Thus, there was no significant difference between the generosity of the French and the Chinese to non-family members over social distances 1~20 (GLM 5), and no apparent effect of the IND-COL subscales (GLM 6). Thus, the greater generosity of the Chinese was, essentially, the product of a kinship premium which resulted in Chinese participants allocating a significantly greater share of the endowments to family members especially at close social distances. Finally, we investigated whether the parameters of the models (a and b for the Constant Sensitivity Model, b and d for the Beta-Delta model, and k and V for the hyperbolic model), correlated with the individual IND-COL scores on the different subscales, on the higher order factors (Ingroup Solidarity and Social Obligation) or indeed on the global IND-COL score. No significant correlations were discovered for the Chinese students with any of the models (Supplementary Tables 1, 3, 5), or for the French with the parameters of the Beta-Delta or the Hyperbolic models (Supplementary Tables 4, 6). However, for the French with the Constant Sensitivity model (Supplementary Table 2), the parameter a showed a significant inverse correlation with the IND-COL subscale Kin and Neighbors/susceptibility to influence. This suggests that for French students the greater their sensitivity to the influence of family and neighbors (a measure of their integrations with society), the broader they set the boundaries of their Ingroup (1/a). The parameter b showed significant inverse correlations with the factors Parents and Spouse/distinctiveness of personal identity, the higher order factor Ingroup Solidarity and Global IND-COL scale. Since high scores reflect greater social integration and b measures sensitivity to social distance, it is entirely coherent that these factors should be inversely correlated. 4. Discussion By adopting a dictator game with real recipients at each social distance, as a paradigm of the social discounting task, our study showed that the Constant Sensitivity model best accounted for social discounting in Chinese students and the Beta-Delta model was best for the French. The Chinese showed significantly greater generosity to family members at close social distances, in agreement with the concept of a strong kinship premium. At greater social distances, there was no significant difference between the generosity of the French and the Chinese. Indeed, multivariate analysis using GLMs showed there was no significant difference between the generosity of the French and the Chinese students for non-family members at any social distance. This suggests that the relative strengths of kinship premium-rather than "cultural cohesion forces"-drives the differences in social discounting between Chinese and French students at different social distances. Cultural comparisons are a fruitful domain for behavioral research. Authors tend to agree that occidental cultures such as in North America and Western Europe tend to be more individualistic than those in Asia or Africa (Markus and Kitayama, 1991). In turn, Asian and African cultures are perceived to be more interdependent. The economic utility of generosity can be envisaged to be an investment in social capital such that today's generosity will be repaid in some way at some time in the future. Thus, one might expect societies characterized by greater interdependence to exhibit greater generosity across the range of social distances (Archambault et al., 2020). Several studies support this by showing that although participants from China and Japan are not more generous than occidental participants, there is less difference between their generosity at low and high social distances when compared to North Americans or Germans (Strombach et al., 2014; Ishii and Eisen, 2018). This has been taken to reflect the greater integration of Asians within their culture as a whole. A thought provoking study compared social attitudes and social discounting in college students in the USA, workers and students in China, and nomadic tribesmen in Kenya (Boyer et al., 2012). The three groups expressed similar levels of trust with respect to their social groups (family, friends, extended family, and neighbors). The Americans and Chinese showed very similar levels of generosity to others at different social distances but the Kenyans showed very little tendency to share with anyone, including close family (Boyer et al., 2012). The authors argued that this reflected the global instability of the Kenyan tribesmen's environment where pastoral tribesmen are at the mercy of potentially devastating famines and droughts as well as aggression from neighboring tribes and intra-tribal rivalries. In such uncertain circumstances, investments in "social capital" may be unlikely to bear dividends. Similar cross cultural comparisons that have included Asian communities living in comparatively deprived environments in Indonesia and Bangladesh, have also failed to find any evidence of hyperbolic social discounting (Tiokhin et al., 2019). Instead, participants showed limited philanthropy toward other members of their communities proportional to need, rather than close social or kinship distance. These studies support that social discounting is a cultural phenomenon that is not universal and which breaks down in harsh economic conditions. However, other studies that have used social discounting tasks to assess prosocial behavior, in non-western, educated, industrialized, rich and democratic countries, reported that generosity declines across social distance, including in India (Hackman et al., 2015), Singapore (Pornpattananangkul et al., 2019), and Kenyan Massai (Archambault et al., 2020). These authors argued that the nature of the dyadic interactions, as measured by social distance, was of equal or even higher importance in these communities, because they rely on well-defined categories of social relations to allocate and access resources. Thus, they explained that the propensity for cooperation and sharing behavior varies with social distance in these societies. Individuals at close social distances are likely to directly share certain common pooled resources on a daily basis, but such day-to-day interdependencies are much less applicable with more socially remote individuals. Thus, discrepancies remain between studies to understand whether generosity depends upon social distances in different societies. Even in the developed world and among highly educated people (e.g., university students) several issues need to be clarified with respect to social discounting. The cross-cultural studies have often used either partially or totally abstract games to compare generosity at different social distances, and have been based on binary decision choices. Therefore, we reinvestigated this issue using a non-hypothetical, non-deceptive experimental design in which the participants and recipients from their social entourage would enjoy the benefits of the participants' decisions. For greater social distances (50 and 100), the beneficiaries were anonymous and therefore, as the participants were informed, the money was donated to a charity. The participants chose freely how to divide the endowments, so their generosity could be measured precisely. Unlike most previous studies the best models to account for the data were the Constant Sensitivity model for the Chinese students and the Beta-Delta model for the French . Interestingly, in a previous study of social discounting by Chinese students the model with the lowest AIC was also found to be the Constant Sensitivity model (Strombach et al., 2014). We found the value of b, which measures the sensitivity to social distance, was significantly higher (p < 0.001) for the Chinese (0.932 +- 0.814) than the French (0.526 +- 0.426). This indicates that their generosity was more sensitive to social distance, which resulted in a swifter decline in generosity as social distance increased. The second parameter, a, defines the limit at which participants separate close from distant relationships. When b is greater than 1, which would appear to be the case for nearly 50% of Chinese participants, social discounting for close individuals (those at social distances less than 1/a) occurs more slowly than when the social distance increases to greater than 1/a. This results in an initial plateau of high generosity to very close individuals. Such behavior is contrary to the hyperbolic and the beta-delta models and would explain why the constant sensitivity model is by far the best for the Chinese participants. The value of a was not significantly different between our groups of Chinese and French students, which suggests that both groups set this distance somewhere between social distance 3 and 5. Interestingly, this also corresponded to the social distance at which the Chinese students ceased to be more generous than the French, and at which both groups, but more particularly the Chinese, ceased to choose a majority of family members as recipients. This pattern is in general agreement with the concept of a kinship premium for generosity (Curry et al., 2013; Booysen et al., 2018a). At social distances greater than 5 the French designated significantly larger numbers of family members than the Chinese. It is interesting that these family members were designated outside the boundary of close social relationships, something significantly rarer for the family members of Chinese students. Moreover, our results indicated that the Chinese were significantly more generous than the French, but only at close social distances, and only to family members. We conducted a regression analysis to explore the sources of the differences between the social discounting of the Chinese and French students. At the first level of analysis (without exploring interactions between variables), the Chinese participants were more generous than the French, participants were more generous to recipients at closer social distances, and participants were more generous to family than non-family members. However, analysis of interactions between these variables (GLM 2, GLM 5) revealed interesting differences between the giving behavior of the Chinese and French. The significant interaction between group and social distance confirmed that the Chinese were more sensitive to social distance than the French, as suggested by the comparison of the parameter b of the Constant Sensitivity model. Thus, although at close social distances the Chinese were more generous than the French, as social distance increased, the difference in generosity decreased between the Chinese and the French. The motor for this difference appeared to be a strong effect of family membership, since the difference in generosity between the Chinese and the French did not hold for non-family members. However, the interaction between Group and Family membership, which directly compares the difference in generosity of the Chinese and French for their family members vs. non-family members at the different social distances, failed to attain significance when all social distances were included in the analysis (GLM 2). We reasoned that this result might be explained by the fact that at social distances 50 and 100 there could be no difference in the generosity of the French and Chinese between family and non-family members because no family members could be allocated to these social distances. Thus, the inclusion of these social distances in the analysis might potentially obscure a genuine effect of family vs. non-family membership between the French and Chinese. Therefore, we conducted GLMs 4, 5, and 6 in which we included only the data for social distances 1 to 20. As a result, we identified that the difference in generosity to family as opposed to non-family members, at the same social distance, was significantly greater for the Chinese than for the French, especially at the closest social distances. That is to say that the kinship premium of the Chinese is significantly larger than that of the French. Furthermore, there was no apparent difference between the generosity of the French and the Chinese for non-family members at any social distance. Interestingly, the kinship premium was especially sensitive to social distance, and even more so among the Chinese than the French participants, as shown by the results of the Nationality x Family member x distance triple interaction (GLM 2, GLM 5). The results of the IND-COL scales seemed to predict results that were very different than those obtained for social discounting. Firstly, the scores for Ingroup Solidarity, a measure of the closeness of the relationship between the participants and their closest social elements, was not significantly different between the French and Chinese and therefore, might be expected to predict similar levels of generosity at close social distances. This idea was reinforced by the results of the three individual subscales that contribute to this higher order scale (CF, PS, and PA), none of which showed significant differences between the French and Chinese. However, in the Social Discounting experiments the Chinese were significantly more generous than the French at close social distances. The Social Obligation scale, as well as the two subscales that contribute to it (KN and NE), indicated that the Chinese were significantly more integrated and collective with more distant elements of their social entourage, and their society as a whole. This might predict that the Chinese should be expected to show higher levels of generosity at greater social distances than the French, however the Social Discounting task revealed no such differences. In a previous study (Booysen et al., 2021), within subject correlations occurred between one of the parameters of the hyperbolic social discounting model (k) and social collectivism or individualism as measured by an IND-COL test, such that more individualistic participants were more sensitive to social distance. We therefore analyzed for correlations between the different model parameters. For the Chinese participants, no significant correlations were found. For the French, inverse correlations between parameters a and b in the Constant Sensitivity model and the scores on several of the IND-COL subscales and the Global IND-COL scores were coherent. Thus, French participants with higher scores for social integration set the limits between close and distant relationships at greater social distances from themselves (lower a) and were less sensitive to social distance (lower b). However, the results of GLM 3 and GLM 6 surprisingly showed that IND-COL subscale scores had no significant capacity to explain the variance of social discounting among the participants. There is a crucial difference between the two types of experiments. In the IND-COL scale, statements by the participant with regard to their social preferences are cost free. Similarly, in the Self-Representation task the estimation of the social distance to others in one's social entourage has no price and no payoff. In our social discounting task, the participants lose money from their own payoff in order to give money to others at each social distance. How much they are "willing to pay" to make that gift provides a real measure of the value of their generosity to that person. Many experiments on social discounting have been performed using either completely hypothetical payoffs or asymmetrical payoffs that only affected the participant, i.e., the payoffs are made to the participant but not the recipient. In such a case, when participants decide to allocate more of the endowment to a hypothetical recipient, they are essentially paying for the pleasure of making a purely hypothetical gift. A decision that homo economicus should reject. This may well impinge on the levels of generosity, especially at close social distances, when the cost might be proportionally higher, and hence result in lower estimations of the kinship premiums at close social distances. Perhaps it is this difference, the fact that one must pay a price to express a higher degree of social integration in the social discounting task, that accounts for the lack of correlation between the degree of social integration expressed in the IND-COL, the Self Representation task and the Social Discounting tasks. The principal difference we found between the Chinese and French students concerns a significantly greater kinship premium for the Chinese than the French. Family and kinship are central to both the Occidental and Chinese cultures, however, it may be that the family, its stability and the importance of family relationships are greater in China than in France. This might be reflected by national statistics. The number of divorces per 100 marriages in France in 2016 was estimated at 55% (Eurostat, 2021), compared to only 3% for China (Ministry of Civil Affairs of the People's Republic of China, 2017). This is also reflected by the fact that 26% of families in France are single parent families compared to 10% in China. These data suggest that the family unit in China is indeed more stable. For example, the majority (almost 60%) of live births in France in 2016 were to unmarried parents (Eurostat, 2018), a statistic we did not find for China. This suggests that the majority of French parents no longer necessarily get married. These data all suggest that formal family relationships may be less concrete in France than China. This impression is also reinforced by the results of our Self-Representation task. The French placed Partners (girlfriend/boyfriend) most frequently as the closest person in their entourage, with mothers second and fathers at a distant fifth position. In contrast the Chinese placed mothers and fathers similarly close at first and second positions. Although, the mean social distance at which Chinese participants placed their "partners" was not significantly greater than that of the French, they placed four other categories (mother, father, brothers and sisters, and best friend) at closer mean social distances. It is interesting that all the French participants indicated they had a partner, whereas only 45% of the Chinese did so. This might suggest that the French were including more trivial relationships as "Partners," however, the fact that on average, this was perceived as the closest relationship the participants had, suggests this was not the case. The greater relative closeness of family members, the stability and the apparent importance of the family unit to the Chinese participants all fit well with the higher magnitude of their kinship premium. As the social distance increases, the value of this kinship premium was discounted rapidly, for both the French and the Chinese, but especially for the Chinese. Furthermore, the proportion of family members falls as social distance increases, and these combined effects result in the increased sensitivity to social distance of the Chinese compared to the French. Data availability statement The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors. Ethics statement Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Author contributions JL: conceptualization, methodology, formal analysis, data analysis, and writing. ED, CQ, and J-CD: conceptualization and writing. JB: data analysis and writing. BC and J-BV: writing--review and editing. ZT: conceptualization. All authors provided the critical revisions. We thank Mohammad Riaz and Jingyu Ma for their help with data collection. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: Click here for additional data file. References Archambault C. Kalenscher T. de Laat J. (2020). Generosity and livelihoods: dictator game evidence on the multidimensional nature of sharing among the Kenyan Maasai. J. Behav. Decis. Mak. 33 196-207. 10.1002/bdm.2153 Ben-Ner A. 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PMC10000292 | Front Vet Sci Front Vet Sci Front. Vet. Sci. Frontiers in Veterinary Science 2297-1769 Frontiers Media S.A. 36908518 10.3389/fvets.2023.1125860 Veterinary Science Original Research Obtaining an animal welfare status in Norwegian dairy herds--A mountain to climb Barry Conor 1 * Ellingsen-Dalskau Kristian 2 Garmo Randi Therese 3 Gronmo Kischel Stine 3 Winckler Christoph 4 Kielland Camilla 1 1Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, As, Norway 2Department for Animal Health, Animal Welfare and Food Safety, Norwegian Veterinary Institute, As, Norway 3TINE SA, Oslo, Norway 4Department of Sustainable Agricultural Systems, Institute of Livestock Sciences, University of Natural Resources and Life Sciences, Vienna, Austria Edited by: Severiano Silva, Universidade de Tras-os-Montes e Alto, Portugal Reviewed by: Yosuke Sasaki, Meiji University, Japan; Mariana Almeida, University of Tras-os-Montes and Alto Douro, Portugal *Correspondence: Conor Barry [email protected] This article was submitted to Animal Behavior and Welfare, a section of the journal Frontiers in Veterinary Science 24 2 2023 2023 10 112586016 12 2022 02 2 2023 Copyright (c) 2023 Barry, Ellingsen-Dalskau, Garmo, Gronmo Kischel, Winckler and Kielland. 2023 Barry, Ellingsen-Dalskau, Garmo, Gronmo Kischel, Winckler and Kielland This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction Knowing the national status of animal welfare, one can identify welfare problems and set a benchmark against which improvements can be compared. Such a status is potentially invaluable for tangible, sustained animal welfare improvement. The objective of this cross-sectional study was to report the status of animal welfare in Norwegian loose-housed dairy herds as assessed using the Welfare Quality(r) Assessment Protocol. Additionally, we investigated if the welfare status varied on a regional basis. Methods In total, 155 herds in eight of Norway's eleven counties were assessed by six trained Welfare Quality(r) assessors. This article presents the herd prevalences of common welfare issues in dairy production in Norway, as well as integrated welfare scores. To determine whether welfare status varied regionally in Norway, generalized linear modeling was used to estimate the mean welfare score for five regions in the four Welfare Quality(r) principles: A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior. These estimated mean welfare scores and their 95% confidence intervals were subsequently assessed for significant variation. Results Encouraging findings included the low mean herd prevalence of 'very lean' cows (3.0%) and the high proportion of cows (59.8%) which could be touched during avoidance distance testing, indicating a positive relationship between stockpeople and their cattle. Challenges affecting the welfare of Norwegian dairy cows were also identified. Of particular concern were issues related to the cows' environment such as prolonged times needed to complete lying down movements and integument alterations. No herd was completely free of changes to the integument and, on average, 77.9% of each herd were affected either mildly or severely. Animal welfare did not appear to vary much between the five regions assessed. Our investigation revealed significant regional variation between two regions (Trondelag and Vestlandet North) in only the Welfare Quality(r) principle Good housing (p < 0.01). Discussion The almost complete absence of regional variation demonstrates that animal welfare status generally varies most at herd level. In conclusion, both welfare challenges and encouraging findings were identified in loose-housed Norwegian dairy herds. To improve animal welfare, herd-specific interventions are most likely to be effective in these herds. animal welfare Welfare Quality(r) dairy cattle loose-housed regional variation Scandinavia prevalence free-stall housing This research was conducted as part of the WelCow project at the Norwegian University of Life Sciences (NMBU). The WelCow project is primarily funded by the Norwegian Agricultural and Food Industry Research Funds, comprised of the Fund for Research Fees for Agricultural Products and the Agricultural Agreement Research Fund (project code 303525). TINE SA, Animalia, and the Norwegian Veterinary Institute contributed through additional funding and the provision of professional time and expertise. pmc1. Introduction Obtaining a welfare status at a national level is challenging, a mountain to climb, so to speak. With a national status, one can identify welfare problems and set a benchmark against which future improvements can be compared, both on a national and herd level. A status of animal welfare is potentially invaluable for tangible, sustained animal welfare improvement. The objective of this cross-sectional study was to report the status of animal welfare in Norwegian loose-housed dairy herds as assessed using the Welfare Quality(r) (WQ(r)) Assessment Protocol for dairy cows (1). Our aim was to report these integrated WQ(r) scores and the underlying observed prevalences of common welfare issues in dairy production in Norway. Additionally, we investigated if the welfare status varied on a regional basis. Animal welfare is high on the political and societal agenda for many countries (2). European citizens are becoming increasingly concerned that food production systems and other activities such as transport should be sustainable. Animal welfare is an important aspect of sustainability and product quality. Negative perceptions may result in consumers refusing to buy products (3). The future of the dairy industry may therefore be dependent on consumers' confidence that the cows producing the milk in their dairy products are treated appropriately. Norway is no exception. The parliamentary white paper specifically aiming to improve animal welfare in production animals announced by the Norwegian government at the end of 2021 is evidence of this (4). Concern about animal welfare is nothing new. Stockpeople have always been concerned about the condition of animals in their care and have tried to ensure that they are healthy and well nourished. Increasingly, this well-being is seen as more than just the absence of illness or injury (5). Instead, the focus is shifting toward what was described by the Farm Animal Welfare Council as "a life worth living". The well-established WQ(r) protocol, for example, includes measures of positive as well as negative welfare. Furthermore, WQ(r) follows the recommendations of the Farm Animal Welfare Council (6) and European Food Safety Authority (7) by utilizing animal-based measures where possible. The WQ(r) assessment is made up of many, diverse animal indicators at both herd and individual level to provide sufficient detail about the welfare status in a herd (8). All indicators included in the WQ(r) protocol were selected on the basis of scientific evidence for their validity, reliability, and feasibility (9, 10). The top-down general framework for the WQ(r) protocol was developed around four welfare principles: A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior. Within these four principles are twelve welfare criteria. Due to the absence of a suitable measure, the criterion thermal comfort is not applied to cattle. Within each of the remaining eleven criteria are one to ten welfare measures. An overview is provided in Table 1. Inversely, the integration of WQ(r) scores follows a bottom-up approach. Based on the relevant measure(s), each criterion is scored on a scale of 0-100, with 100 being the best possible welfare. In turn, these criteria scores are combined to generate a score from 0 to 100 for each of the four principles. These four principle scores are ultimately combined to assign the herd to one of four categories: "Excellent", "Enhanced", "Acceptable", or "Not classified". A full description of the score integration can be found in the WQ(r) protocol (1). Table 1 Summary of the structure of Welfare Quality(r) applied to dairy cattle including principles, criteria, and measures. Principle Criterion Measure A. Good feeding 1. Absence of prolonged hunger Body condition score 2. Absence of prolonged thirst Provision of water B. Good housing 3. Comfort around resting Behavior at lying Cleanliness of cows 4. Thermal comfort No measure available 5. Ease of movement Possibility for cows to move freely C. Good health 6. Absence of injuries Lameness Integument alterations 7. Absence of disease Ocular discharge Nasal discharge Coughing Hampered respiration Vaginal discharge Diarrhea Somatic cell count Dystocia Downer cows Mortality 8. Absence of pain caused by management procedures Disbudding/dehorning Tail docking D. Appropriate behavior 9. Expression of social behavior Agonistic behaviors 10. Expression of other behaviors Access to pasture 11. Good human-animal relationship Avoidance distance test 12. Positive emotional state Qualitative behavior assessment Even if a sufficient sample of representative herds across the country were assessed, a single overall status may mask meaningful regional variations. Such geographical variations in dairy cow welfare have been alluded to in other studies (11, 12). The Norwegian mainland is long, stretching across 13deg of latitude. The glaciated terrain consists of rugged mountains broken by fertile valleys. The coastline is relatively mild due to the Gulf Stream while the north is predominantly arctic tundra. As a result, the typical climatic conditions vary between the five regions for which animal welfare data were collected. For example, an area in the west (Vestlandet North) had a 30-year cumulative mean annual precipitation almost two and a half times greater than an area in the southeast (Ostlandet South). Similarly, lowland areas in the southeast had a 30 year cumulative mean annual temperature of 6.41degC compared to 0.61degC in mountainous parts of the east (Ostlandet North) (13). We hypothesized that the score for the four overarching WQ(r) principles would vary between the five regions in which welfare was assessed. Geographical diversity may influence the welfare of cattle in several ways. The amount of time that dairy cows spend outside at pasture each year, the composition of feed available, and the prevailing housing designs (for example, insulated or non-insulated barns) may vary depending on the regional climate. In turn, this variation may influence dairy cow welfare. If welfare is found to vary significantly from region to region, this could have important implications both for the provision of a national status and for targeting regionally specific welfare interventions. To our knowledge, a primarily animal-based welfare assessment of this scale has never been previously conducted in Norwegian loose-housed dairy herds. Specific topics relevant to dairy cow welfare have been studied in Norwegian dairy herds, for example skin lesions (14); mastitis (15); lameness (16); and body condition (17), but never in combination using an integrated animal welfare assessment protocol. Similarly, regional variations of the welfare status in Norwegian dairy herds have not been formally investigated. Previous studies have indicated that, contrary to what has happened in other European countries, Norwegian dairy producers have not faced a problem of consumer distrust. Animal welfare in Norway has been primarily governed and regulated by the issuing of statutory regulations that often go beyond EU standards (18). The legislative requirement for pasture access in the 2004 "Regulations for the Keeping of Cattle" (19) is an example of this. The present study will provide insight into whether the reality of animal welfare on-farm, as assessed using the WQ(r) protocol, aligns with the high legislative standards and consumer expectations in Norway. Such information may be of interest to dairy industry stakeholders in other countries as they consider how to address growing public concern about animal welfare. Additionally, should regional variation be detected, it would facilitate the implementation of regionally specific welfare interventions in Norway. Awareness of the potential for regional variation could prove useful beyond Norwegian conditions, in any country with a welfare status which may similarly vary. 2. Materials and methods 2.1. Herd selection The herds were selected from the Norwegian Dairy Herd Recording System (NDHRS), operated by Mimiro AS, a subsidiary of TINE SA. TINE SA is Norway's largest producer, distributor, and exporter of dairy products (20), representing ~97.5% of Norwegian dairy herds. Herds eligible for inclusion in the study were members of TINE SA and participants in NDHRS. The study population was selected to be broadly reflective of Norway's expected future dairy herds by only including loose-housed herds and herds of 25-100 standardized cow-years in size at the time of selection. Herds using tie-stall housing, representing 54.2% of the herds in Norway (21), were excluded as this housing system is banned completely from 2034 onwards (22). In 2021 loose-housing herds accounted for 67.3% of the total number of dairy cows in Norway (21). The average number of standardized cow-years within TINE dairy herds in 2021 was 30.9, increased from 22.1 in 2011 (21), with the desired range of standardized cow-years for inclusion representing the trend toward larger herd sizes in Norway. Geographically, the herds were selected from the municipalities located in nine of the eleven counties in Norway. Herds from the two most northern counties (Nordland and Troms og Finnmark), ~10% of the herds in Norway (21), were excluded due to budgetary constraints. From the target population of all loose-housed Norwegian dairy herds (n = 2950) (21) a list was prepared of herds which met the remaining inclusion and exclusion criteria of the project (n = 1244) using SAS 9.4 software (23). The list was sorted by producer identification number, the first four digits of which are related to geographical location. A geographically stratified pseudorandom sample of potential herds was chosen from this list by selecting every 4th herd (n = 311). Following inspection of the list of selected herds, two herds were deemed ineligible for participation as they were no longer producing milk. A list of active selected herds (n = 309) was prepared. Figure 1 summarizes the selection and recruitment process. Figure 1 Euler diagram visualizing the selection and recruitment process. To minimize the influence of routine claw trimming on lameness scoring, WQ(r) specifies that herds should not be assessed until at least 28 days after routine claw trimming. Additionally, for practical reasons, lactating cows must be housed during the visit. Due to these constraints, scheduling practicalities, budgetary limitations, and potential participant hesitancy we anticipated it would be possible to visit ~50% of the eligible selected herds. 2.2. Herd recruitment All 155 herds participated voluntarily. Their geographical distribution can be seen in Figure 2. Recruitment occurred over two phases, one passive and one active, as described below. To maximize participation, several methods of contacting producers (e-mail, SMS, telephone call, and word-of-mouth) were attempted. Figure 2 Map of central and southern Norway showing the five regions investigated, the eligible herds which were visited, and the eligible herds which were not visited. 2.2.1. Passive recruitment Initially, all 309 active selected herds were emailed by the TINE Member Center, the group responsible for internal communication with members of TINE SA. The email contained information about the project and a link to a web-based questionnaire with four questions (24). After confirming their producer identification number and name, potential participants were asked if they were interested in participating and, if so, they were asked for their preferred contact telephone number. SMS nudges were sent three and eight days after the initial email to remind the potential participants to respond to the questionnaire. We informed the TINE advisors assigned to each of the selected herds about the project by email and asked them to encourage their clients to complete the questionnaire. Herds were classified as passively recruited if they expressed interest in participating through the initial questionnaire. All active selected herds were plotted geographically using GPS coordinates in Google MapsTM (25). To ensure the sample was broadly representative geographically, the herds were divided into approximate geographical areas. The herds in each area which had expressed interest in participating were contacted by telephone in order of appearance on the list of active selected herds. If possible, a visit was arranged on an appropriate date. When visits were arranged with approximately half of the herds in an area, herds in a new area were contacted. 2.2.2. Active recruitment In areas where an insufficient number of herds were recruited passively, herds which had not explicitly stated they did not wish to participate in a questionnaire response were contacted by telephone. Their participation was requested and if they were willing a visit was arranged. These herds were classified as actively recruited because their recruitment required a direct telephone conversation rather than expressing interest of their own volition through the questionnaire. They were contacted by the assessors in order of appearance on the list of active selected herds until visits were arranged with ~50% of herds in an area. 2.3. Regions For the purpose of investigating regional variation, the 155 herds were assigned to one of five regions corresponding to their administrative district within TINE SA. These administrative districts are based on traditional geographical divisions of Norway. The five regions were Trondelag (n = 43), Ostlandet South (n = 38), Ostlandet North (n = 29), Vestlandet South (n = 24), and Vestlandet North (n = 21). The five regions and their herds are shown in Figure 2. 2.4. Assessor training Six assessors, three veterinarians and three ethologists were trained to use the WQ(r) protocol in a three-day course provided by a delegate of the WQ(r) Network. All assessors had previous experience of handling and body condition scoring dairy cattle. Due to international travel restrictions at the time of training, the theoretical component of the course was delivered online in a classroom environment. Practical aspects of the course were performed locally under remote supervision and the assistance of two assessors who had previously completed additional training. The course concluded with an online assessment of interobserver reliability (IOR) using photographs and videos. The percentage agreement with the silver standard reference values ranged from 73 to 100%. The IOR was evaluated using statistical techniques by the course provider and deemed to be acceptable for all measures except for those related to behavior observations. This was consistent with the prior experience of the course provider. For this reason, extra attention was placed on these behavioral assessments during the shadowed visits which followed the course. Each assessor performed one to two complete shadowed visits accompanied by a more experienced assessor. These shadow visits occurred prior to undertaking visits independently. Two herds not included in the list of randomly selected herds were used for shadow visits but not included in the analysis. All assessors were subsequently WQ(r) certified. 2.5. Data collection A full WQ(r) assessment was performed for each herd between April 2021 and January 2022 as described by the WQ(r) protocol (1). All of the herds were managed in a broadly similar manner. Cows were housed indoors on rubber-matted cubicles for most of the year with variable amounts of pasture access during the summer months. Cows were milked using either automatic milking systems (AMS) or milking parlors. Forage was provided ad libitum at a feed face with supplies being refreshed up to several times daily. Concentrate feeding took place primarily in the AMS or milking parlor, with additional concentrate feed often being provided by concentrate feed dispensers. The welfare assessment data were recorded either on paper using the protocol's example recording sheets; using an Excel recording sheet; or using an online application developed for the purposes of data collection and WQ(r) score calculation (26). Sick or freshly calved cows were excluded. The data collected for each measure and the sources of the data are summarized in Table 2. For measures based on individual animals the sample size depended on the size of the herd. The number of individuals recommended by the WQ(r) protocol (1) were chosen using systematic sampling by selecting every second animal at the feed face (28) while performing the avoidance distance test. Simultaneously, each animal was alternately designated to clinical assessment of its left or right side. Sampling was divided between at least two separate time periods. The same individuals were assessed for avoidance distance and clinical measures whenever possible. Table 2 Summary of the data collected for each measure of the Welfare Quality(r) protocol and the sources of the data (*on-farm observation or clinical assessment; **interview with farmer or livestock manager; ***Norwegian Dairy Herd Recording System). Measure Associated data and source Body condition score % very lean cows*[corresponding to a score < 2.5 in the grid of Edmonson et al. (27)] Provision of water Number of drinkers*; length of water troughs*; cleanliness of water points*; water flow rate* Behavior at lying Mean time to lie down*; % cows colliding with housing equipment when lying down*; % of cows lying partly or completely outside of the lying area* Cleanliness of cows % cows with dirty udder*; % cows with dirty hindquarters*; % cows with dirty lower legs* Thermal comfort Criterion not assessed Possibility for cows to move freely Presence of tethering* Lameness % mildly lame cows*; % moderately or severely lame cows* Integument alterations % cows with mild integument alterations (hairless patch)*; % cows with severe integument alterations (lesion or swelling)* Ocular discharge % cows with ocular discharge* Nasal discharge % cows with nasal discharge* Coughing Number of coughs per cow per 15 min* Hampered respiration % cows with hampered respiration* Vaginal discharge % cows with vaginal discharge* Diarrhea % cows with diarrhea* Somatic cell count % cows with somatic cell count >400,000 in the previous three milk recordings*** Dystocia % cows affected by dystocia in the previous 12 months** Downer cows % cows recumbent for more than 24 h in the previous 12 months** Mortality % cows dead, euthanized, or emergency slaughtered on-farm in the last 12 months**/*** Disbudding/dehorning Procedure used for disbudding/dehorning**; use of anesthetics**; use of analgesics** Tail docking N/A in Norway as forbidden as a routine management procedure Agonistic behaviors Number of headbutts per cow per hour*; number of displacements, bouts of fighting, and occurrences of chasing or chasing up per cow per hour* Access to pasture Number of days per year with access to pasture**; number of hours per day with access to pasture** Avoidance distance test % cows which can be touched*; % of cows which can be approached between 10 and 50 cm*; % cows that can be approached between 60 and 100 cm*; % of cows that cannot be approached closer than 110 cm* Qualitative behavior assessment Values for 20 descriptors (0-125mm scale)* The vast majority of cows assessed were Norwegian Red (NRF). The body condition scoring system used by WQ(r) is dependent on whether the cow is of dairy or dual-purpose type. To account for neither of the WQ(r) protocol's body condition scoring systems being fully suitable for NRF, a previously published five-point body condition scoring grid (27) adjusted for NRF (29) was used to assess body condition in increments of half points. The body condition score for NRF was recorded as a WQ(r) body condition score registration using cut-off points agreed with a member of the WQ(r) Network. "Very lean" corresponded to a score < 2.5, "Normal" was 2.5-3.5, and "Very fat" was >3.5. The body condition of other breeds was scored according to the WQ(r) system. Some data were self-reported by the farmer from on-farm records or memory. These included the number of cases of dystocia, the number of downer cows, and the number of cows which died, were euthanized or were emergency slaughtered on-farm during the 12 months prior to the visit. Additionally, the number of days of pasture access per year and the number of hours of pasture access during those days was self-reported. The definition of pasture extended to any vegetation covered outdoor area, even if it did not contribute to the cows' nutritive requirements. Self-reporting was preferred as this aligned most accurately with the WQ(r) definitions. When dystocia data were missing in the dataset (n = 7), the mean value from the other herds was used instead as this was considered by the authors to be broadly reflective of Norwegian conditions. When mortality data were unavailable through self-reporting, the mortality records for the farm were accessed through the NDHRS and these data used. For every herd, data for the average number of lactating animals and the number of calvings which took place in the herd during the 12 months prior to the visit were retrieved from the NDHRS following the on-farm assessment. These data were used to calculate the percentage mortality, dystocia, and downer cows during that time period. Somatic cell count (SCC) data for each cow for the last three milk recordings prior to the visit were also obtained from NDHRS and the percentage of cows with a SCC >=400,000 cells per milliliter in at least one of these milk recordings was calculated. 2.6. Welfare Quality(r) score calculation The four principle and eleven applicable criteria scores were calculated based on the formulae provided in the updated version of the WQ(r) protocol (1). These formulae were programmed into an online application designed for the purpose of data collection and calculation of integrated WQ(r) scores (26). All data collected using paper recording sheets or the Excel sheet were transferred into the online application's database for the purpose of score calculation. All of the raw data and the calculated scores were exported from the database in.csv format for analysis. The application automatically assigned each herd to a WQ(r) category based on which aspiration thresholds defined by the WQ(r) protocol were met by its principle scores. Herds were classified as "Excellent" if all principle scores were over 55 and two were over 80; "Enhanced" if all principles scores were over 20 and two were over 55; "Acceptable" if all principles scores were over 10 and three were over 20; and "Not classified" if they did not meet the requirements for "Acceptable". 2.7. Statistical analysis All data analyses were performed using Stata 16 (30). The exact operations used in Stata stand in quotation marks and are italicized. All 155 herds visited were included in the analyses. 2.7.1. Descriptive statistics The integrated WQ(r) scores (4 principles and 11 criteria) and observed prevalences of common welfare issues and other welfare related herd level summary data (n = 34) were reported in table format, organized within the structure of WQ(r) as described in Table 1. To provide more detailed descriptions of the data, data distributions and the relationships between variables were assessed graphically as necessary. Examples include the relationship between ocular and nasal discharge and the month of the visit, as well as the linear relationship between the proportion of very lean animals and the proportion of dairy-type animals on-farm. 2.7.2. Statistical modeling and regional variation Generalized linear modeling (GLM) (31) was used to investigate whether the welfare status varied depending on region. In total, four models were built, one for each principle: A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior. The dependent variable for each model was the eponymous continuous principle score ranging from 0 to 100. As region was the variable of primary interest, a categorical independent variable denoting the five regions was included in all four models as a fixed effect. The distribution of the dependent variable and its transformations, based on a subset of the ladder of powers (32), were screened initially using the "gladder" command. The link function corresponding to the most normally distributed transformation was included as a component of the model. The Gaussian family function was included in all four models due to the distribution of the dependent variable or its chosen transformation. Each model was built using a forward selection process. The relationship between the independent variables and the dependent variables was assessed univariably. A conservative initial inclusion criterion of P < 0.20 was used during univariable screening, however, biological plausibility took precedence throughout the model building process. Independent variables were retained following univariable screening process regardless of their statistical relationship to the dependent variable if it was biologically justifiable. Potential biological relationships were identified using directed acyclic graphs (33). The independent variables assessed univariably were assessor (coded 1-6); milking system (AMS or parlor); recruitment method (passive or active), and herd size (continuous). Herd size, as the only continuous independent variable, was plotted against the dependent variable using locally weight scatterplot smoothing (LOWESS) (34) to assess whether a linear relationship was present or not prior to univariable screening. Such a relationship only existed between herd size and the principle B. Good housing. Despite training and IOR testing, significant assessor effects were detected during univariable screening for the models B. Good housing, C. Good health, and D. Appropriate behavior. Furthermore, the distribution of herds visited by different assessors was not even across the five regions. It was concluded that assessor effects could act as a confounder for potential regional effects. Therefore, it was necessary to include the assessor variable in all models intended to determine the extent of regional variation. During multivariable modeling, independent variables carried forward from the univariable screening were retained if they improved the explanatory power of the model and were biological plausible, resulting in a best fitted model for each principle. The best fitted models are reported in Table 3. As all models were nested during the building process, the models were assessed using Wald Chi2 Test scores and their significance values (35) to determine the best fitted model. Table 3 Details of the four best fitted generalized linear models (A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior) used to investigate regional variation. Welfare Quality(r) Principle (Dependent Variable) Best Fitted Model (Independent Variables) Model Intercept (Scale 0-100) Std. Err. (Intercept) Homoscedasticity Normality Link Family Wald Chi2 Test (Prob > Chi2) A. Good feeding i.region i.assessor 60.5 4.3 Yes Yes Identity Gaussian 11.0 (0.3) B. Good housing i.region i.assessor herd_size 58.8 2.3 Yes Yes Identity Gaussian 52.2 (< 0.01) C. Good health i.region i.assessor i.recruit i.milking_system 37.8 1.0 Yes Yes Log Gaussian 46.52 (< 0.01) D. Appropriate behavior i.region i.assess i.recruit 49.5 1.7 Yes Yes Identity Gaussian 16.6 (0.1) Post estimation, the linear prediction and deviance residuals of each model were calculated. Homoscedasticity was assessed by plotting these two sets of residuals against each other on a two-way scatterplot. Normality of the deviance residuals was assessed visually by two methods. First by producing a histogram and secondly by plotting the quantiles of the deviance residuals against the quantiles of normal distribution. The details of the intercepts of the best fitted models used, the standard errors of their intercepts, their post estimation results, and their Wald Chi2 Test scores with significance values are provided in Table 3. The "margins" command with region as the factor variable was used to calculate the estimated mean for each of the five regions based on the best fitted models A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior. The estimated means were summarized on a regional basis in table format. Where a significant difference was found between regions, this was demarcated in the table in bold. The significance threshold was set at P = 0.05. Additionally, they were visualized with their 95% confidence intervals using the "marginsplot" command. 3. Results 3.1. Participating herds The 155 herds assessed had an average herd size of 52 cows with a range from 18 to 117 cows. AMS were present in 89% of the herds (n = 138) and the remaining 11% used milking parlors (n = 17). The proportion of the cow assessed for individual level measures was between 46 and 100% per herd. On average, 74% of the eligible lactating cows and heifers in each herd were assessed individually. The mean proportion of NRF in the herds assessed was 92.7%. There were slightly more actively recruited herds (51.5%) than passively recruited herds (48.4%). 3.2. Welfare Quality(r) categories More than half of the herds, 55.5% (n = 86), were classified as "Enhanced" based on their WQ(r) assessment. Of the remaining herds, 43.2% (n = 67) were placed in the "Acceptable" category and 1.3% (n = 2) were deemed "Unclassified". None of the herds attained the highest WQ(r) classification of "Excellent". 3.3. Welfare Quality(r) scores and measures Welfare Quality(r) principle and criteria scores are shown in Table 4. The observed prevalences of common welfare problems as well as other herd level welfare measures not expressed as prevalences are displayed in Table 5. Table 4 Summary of Welfare Quality(r) scores in Norwegian loose-housed dairy herds (n = 155) showing the mean, standard deviation of the mean, median, maximum, and minimum for each value. Welfare Quality(r) Principles & Criteria Mean Std. dev. Median Min. Max. A. Good feeding 56.0 27.8 60.9 9.1 100.0 1. Absence of prolonged hunger 83.5 19.7 85.7 19.3 100.0 2. Absence of prolonged thirst 54.9 32.7 60.0 3.0 100.0 B. Good housing 63.4 9.4 63.8 40.2 93.3 3. Comfort around resting 41.9 14.9 42.5 5.0 89.3 4. Thermal comfort - - - - - 5. Ease of movement 100.0 0.0 100.0 100.0 100.0 C. Good health 38.1 8.2 37.2 20.0 66.2 6. Absence of injuries 43.0 13.5 42.9 14.6 88.9 7. Absence of disease 35.0 14.3 33.3 10.0 86.0 8. Absence of pain induced by management procedures 75.0 0.0 75.0 75.0 75.0 D. Appropriate behavior 47.6 10.0 48.3 16.3 67.5 9. Expression of social behaviors 53.9 18.9 54.4 9.3 96.8 10. Expression of other behaviors 47.7 16.3 53.6 0.0 100.0 11. Good human-animal relationship 77.7 12.6 79.2 35.6 97.4 12. Positive emotional state 49.9 12.7 51.5 15.0 79.6 Scale 0-100. Table 5 Summary of observed prevalences and other herd-level registrations related to animal welfare in Norwegian loose-housed dairy herds (n = 155) showing the mean, standard deviation of the mean, median, maximum, and minimum for each value. Welfare Value Mean Std. dev. Median Min. Max. Very lean body condition score 3.0 % 4.9 % 1.9 % 0.0 % 34.5 % Very fat body condition score 12.1 % 12.1 % 9.1 % 0.0 % 61.3 % Mean time to lie down in seconds 6.2 0.9 6.1 4.3 9.4 Collisions with housing equipment when lying down 11.4 % 14.2 % 7.7 % 0.0 % 90.0 % Lying partly or completely outside the lying area 2.8 % 4.6 % 0.9 % 0.0 % 25.5 % Dirty udder 17.0 % 14.0 % 13.3 % 0.0 % 76.6 % Dirty hindquarter 33.7 % 21.5 % 31.8 % 0.0 % 94.6 % Dirty lower hind legs 62.6 % 23.6 % 64.0 % 4.9 % 100.0 % Mildly lame cows 11.1 % 7.5 % 9.4 % 0.0 % 36.4 % Moderately or severely lame cows 2.9 % 4.0 % 2.3 % 0.0 % 25.0 % Mild integument alterations 45.3 % 13.8 % 46.3% 4.3 % 78.6 % Severe integument alterations 32.6 % 16.9 % 30.0% 0.0 % 86.4 % Tarsal hairless patches 47.7 % 15.9 % 48.5 % 8.9 % 79.5 % Tarsal lesions 7.4 % 7.8 % 4.3 % 0.0 % 41.0 % Tarsal swellings 4.2 % 7.9 % 2.5 % 0.0 % 66.7 % Carpal hairless patches 29.4 % 13.7 % 27.3 % 0.0 % 71.9 % Carpal lesions 1.5 % 3.5 % 0.0 % 0.0 % 20.0 % Carpal swellings 4.7 % 5.2 % 3.1 % 0.0 % 27.3 % Neck/shoulder/back hairless patches 8.0 % 8.4 % 5.4 % 0.0 % 33.3 % Neck/shoulder/back lesions 0.5 % 1.5 % 0.0 % 0.0 % 10.3 % Neck/shoulder/back swellings 5.1 % 10.0 % 0.0 % 0.0 % 65.9 % Ocular discharge 15.8 % 13.8 % 13.4 % 0.0 % 60.0 % Nasal discharge 6.8 % 7.6 % 3.6 % 0.0 % 41.7 % Vaginal discharge 0.9 % 1.7 % 0.0 % 0.0 % 11.1 % Diarrhea 8.8 % 10.6 % 6.1 % 0.0 % 57.1 % Hampered respiration 0.3 % 0.01 % 0.0 % 0.0 % 12.9 % Dystocia 3.3 % 2.9 % 2.6 % 0.0 % 18.5 % Downer cows 1.3 % 1.8 % 0.0 % 0.0 % 8.0 % Mortality 4.5 % 3.6 % 3.6 % 0.0 % 16.7 % Somatic cell count >400,000 in the previous three milk recordings 15.2 % 6.9 % 14.0 % 0.0 % 33.3 % Number of coughs/cow/15 min 0.10 0.09 0.08 0.00 0.42 Number of headbutts/cow/hour 0.74 0.42 0.66 0.00 2.23 Number of displacements (including fighting, chasing, and chasing up)/cow/hour 0.72 0.41 0.61 0.00 2.19 Number of days/year with 8 or more hours of access to pasture 109 47 120 0 365 0 cm avoidance distance test score 59.8 % 19.4 % 61.5 % 6.7 % 94.1 % 10-50 cm avoidance distance test score 33.7 % 14.9 % 32.5 % 5.9 % 71.7 % 60-100 cm avoidance distance test score 5.6 % 7.1 % 3.2 % 0.0 % 43.3 % 110-200 cm avoidance distance test score 0.9 % 2.0 % 0.0 % 0.0 % 10.0 % 3.3.1. Good feeding The mean score for the principle good feeding across all herds was ~56 but this varied hugely from < 10 to the maximum of 100 between herds. As can be seen in Table 4, the standard deviation of the mean herd score for the principle good feeding was far higher than the standard deviation of the mean for the other three principle scores. Good feeding was, therefore, the principle with the greatest variation between herds. 3.3.1.1. Absence of prolonged hunger and thirst The criterion absence of prolonged hunger was scored, on average, higher than the mean score for the criterion absence of prolonged thirst. Its minimum was over 16 points higher. The scores for absence of prolonged hunger were skewed to the left, indicating that the majority of herds did not have many cows experiencing prolonged hunger. Despite this, the scores for this criterion were variable, with the lowest scoring herd achieving less than 20 points. The criterion absence of prolonged thirst had the highest standard deviation of the mean of any of the WQ(r) scores which contributed to the herd variation seen at the principle level for good feeding. 3.3.1.1.1. Body condition score The criterion for absence of prolonged hunger is calculated based on the proportion of cows in each herd with a very lean body condition score. As shown in Table 5, the mean herd prevalence for 'very lean' cows was just under 3%. This data was heavily right skewed, with only 21% of herds having more than 5% 'very lean' animals. Even so, in one herd more than one third of the animals were classified as 'very lean', a clear example of variation between herds. On the other hand, the mean herd prevalence for 'very fat' cows was just over 12%. Therefore, the mean herd prevalence of cows with a normal body condition score was 85%. At herd level, LOWESS showed a positive linear relationship between the proportion of very lean animals and the proportion of cows classified as dairy-type breeds by WQ(r). 3.3.2. Good housing The mean score for the principle good housing was just above 63 points, as shown in Table 4. No herds scored below 40 points for this principle, but this is because each herd scored maximum points for the contributing criterion ease of movement. Less variation from herd to herd, at principle level, was seen as a result. The range of scores for this principle was smaller (53 points) than the range for the principle good feeding. Furthermore, the standard deviation of the mean for this principle was one third of the size of the standard deviation of the mean for the principle good feeding. 3.3.2.1. Comfort around resting Comfort around resting was the only criterion that could vary within the good housing principle. The criterion thermal comfort lacked a suitable measure, so it was excluded from the assessment. The exclusion of tie-stall herds from the study resulted in the full score awarded to every herd for the criterion ease of movement. The consistent high scoring of the ease of movement criterion appears to have compensated, at a principle level, for the relatively low scoring for the criterion comfort around resting. Nearly three quarters of the herds scored < 50 points for comfort around resting and two herds scored < 6 points. 3.3.2.1.1. Time needed to lie down WQ(r) assigns the mean time needed to lie down for each herd to one of three categories: normal (< 5.2 s); moderate problem (5.2-6.3 s); or severe problem (>6.3 s). Of the herds assessed, 15.5% of herds were classified as normal, 41.3% as having a moderate problem, and 43.2% a severe problem. That herds were classified across all three categories highlights the variation at herd level. The mean time across all herds was only slightly below the border between a moderate and a severe problem. 3.3.2.1.2. Animals colliding with housing equipment during lying down As can be seen in Table 5, there was a large amount of variation between herds for this measure. The data was skewed heavily toward 0%, suggesting this was not an issue for the majority of herds, but a number of herds did have problems with cows colliding with housing equipment during lying down movements. In 15 of the herds, over 30% of lying down movements resulted in collisions. These herds are classified by WQ(r) as having a severe problem. In one herd in particular, nine out of ten recorded lying down movements resulted in a collision. 3.3.2.1.3. Animals lying partially or completely outside of the lying area The proportion of animals in each herd observed lying partly or completely outside the lying area was similarly skewed toward lower prevalences. A little over one fifth of the herds assessed were classified by WQ(r) as having a severe problem, meaning they had more than 5% of their animals lying partly or completely outside the designated lying area. While a quarter of cows in one herd were recorded as lying out, more than half of the herds had < 3% of cows lying partially or completely outside the lying area as demonstrated by the median score in Table 5. 3.3.2.1.4. Cleanliness The scoring for all three cleanliness measures followed an approximately normal distribution. As described in Table 5, lower hind legs were most commonly scored as dirty, followed by upper hind legs and udders, respectively. Based on the WQ(r) cleanliness classifications, the mean prevalence for all herds for dirty lower and upper hindlegs would be classified as a severe problem. The mean prevalence of dirty udders would be classed as a moderate problem. There was not a single herd where all of the lower hind legs were scored as clean, with all herds having some cows with dirty lower hind legs. In 21 herds over 90% of the cows were scored as having dirty lower hind legs. 3.3.3. Good health Table 4 showed that this was consistently the lowest scored principle across the herds and the only principle to have a mean score below 40 points. It also showed the least variation, with the lowest standard deviation of the mean of the four principle scores. No herd achieved a score higher than 67 points. 3.3.3.1. Absence of injuries Injuries were frequently observed, as can be seen in Table 5. On average, 14.0% of cows in each herd were scored as being lame to some extent, either mildly or moderately/severely. Integument alterations were even more frequent, with 78.2% of individual animals assessed having at least one hairless patch, lesion or swelling on their body. More than half of the affected animals were scored as having mild changes to the integument, meaning they had at least one hairless patch but no lesions or swellings. As can be seen in Table 5, changes in the tarsal region were by far the most common, followed by carpal changes and changes to the neck, shoulder, and/or back. No herds were found to be completely free of integument alterations. The herd prevalences for these measures were variable between herds, especially for tarsal hairless patches, carpal hairless patches, and swellings on the neck, shoulder, and/or back which all had ranges >65%. Hairless patches and swellings on the neck, shoulder, or back, for example, were absent in the majority of herds but very frequent in certain herds. 3.3.3.2. Absence of disease The criterion absence of disease is made up of ten disease-related measures which are reported in Table 5. These measures are compared to threshold values defined by WQ(r), "warning" and "alarm". If the warning threshold is surpassed, it indicates that there may be a problem in the herd, and it could be beneficial to investigate this further. If the alarm threshold is breached, then it is recommended by the WQ(r) protocol that action be taken to address the problem identified. High somatic cell count and ocular discharge, both clinical signs of disease issues, were most commonly identified. The mean herd prevalences of nasal discharge, diarrhea, dystocia, downer cows, and mortality were all < 10%. Vaginal discharge and hampered respiration were very rarely encountered. On average, 0.1 coughs were detected per cow per 15 minutes of observation time. The prevalence of these clinical measures varied between herds. For all contributary measures, there were herds in which no animals scored were affected by that particular issue. In other herds, as many as half of all animals scored were affected, depending on the measure. As shown in Table 5, the mean values for ocular discharge and diarrhea were both higher than their alarm thresholds, 6 and 6.5%, respectively. The mean values for nasal discharge, high somatic cell count, dystocia, and mortality did not meet their alarm thresholds but did surpass their warning thresholds of 5, 8.75, 2.75, and 2.75%, respectively. Other values which contributed to the criterion for absence of disease (downer cows, vaginal discharge, and hampered respiration) were below their warning thresholds. 3.3.3.2.1. Somatic cell count The mean prevalence of cows with a somatic cell count >400,000 in at least one of last three recordings prior to the visit was over 15%. This exceeded the warning threshold, as described above, and was just below the alarm threshold of 17.5%. 3.3.3.2.2. Ocular and nasal discharge The prevalences of nasal and ocular discharge showed a seasonal pattern when plotted against the month of the visit. Both increased during the late spring and summer months before decreasing in the autumn. 3.3.3.3. Absence of pain induced by management procedures The criterion score for absence of pain induced by management procedures was the same for all 155 herds assessed. 3.3.4. Appropriate behavior The scoring of this principle was approximately normally distributed and varied between herds through a range of over 50 points. Of the four criteria contributing to this principle, good human-animal relationship was the most highly scored, followed, respectively, by expression of social behaviors, positive emotional state, and expression of other behaviors. 3.3.4.1. Expression of social behaviors The criterion expression of social behavior is scored based on the number of agonistic behaviors observed per cow per hour. These behaviors are divided into two measures, headbutts and displacements, with fighting, chasing, and chasing-up being considered together with displacements. The scores obtained varied from herd to herd through almost the entire possible range of scores. The data were approximately normally distributed. 3.3.4.2. Expression of other behaviors On average, the herds assessed allowed cows out to pasture for approximately three and a half months per year. The number of days varied from herd to herd, with two herds allowing their cows year-round access to a vegetation-covered outdoor area and five herds (at least one in each region) providing nothing that would be described by WQ(r) as pasture. This was the only WQ(r) score in the study that spanned the full possible range from 0 to 100 points. 3.3.4.3. Good human-animal relationship The criterion score for good human-animal relationship is based on the avoidance distance testing of a sample of individual cows. The outcome of each individual avoidance distance test is assigned by WQ(r) to one of four categories: the cow could be touched; the cow could be approached close than 50 cm but not touched; the cow could be approached between 50 and 100 cm; or the cow could not be approached closer than 110 cm. On average, almost two thirds of cows could be touched by the assessor. Approximately one third of individual cows could be approached closer than 50 cm but not touched. Less than 1% of cows could not be approached closer than 100 cm. The human-animal relationship did vary from herd to herd, however, as despite nearly half of herds scoring over 80 points, eight herds scored < 50 points. 3.3.4.4. Positive emotional state The criterion score for positive emotional state was based on qualitative behavioral analysis of the herd. The scoring was approximately normally distributed and varied between herds with a range of 64.6 points from minimum to maximum. 3.4. Regional variation The estimated mean WQ(r) principle scores for the five regions are reported in Table 6. The only principle that showed significant regional variation in the estimated mean principle scores was B. Good housing. The estimated mean score for Trondelag was over 7 points lower than the mean score which was estimated for Vestlandet North. These estimated mean scores are demarcated in Table 6 in bold. Figure 3 visualizes the mean scores for region with their 95% confidences intervals. Visual assessment of the 95% confidence intervals for these two regions for the principle B. Good housing demonstrates the significant difference. The estimated mean scores for the principles A. Good feeding, C. Good health, and D. Appropriate behavior did not vary significantly between the five regions. Table 6 Summary of estimated mean regional Welfare Quality(r) principle scores based on the generalized linear models A. Good feeding, B. Good housing, C. Good health, and D. Appropriate behavior. Welfare Quality(r) Principle Trondelag (n = 43) Ostlandet S (n = 38) Ostlandet N (n = 29) Vestlandet S (n = 24) Vestlandet N (n = 21) A. Good feeding 58.5 55.5 48.0 52.1 67.2 B. Good housing 60.3 65.5 62.1 63.9 67.5 C. Good health 35.9 40.1 39.5 39.2 36.1 D. Appropriate behavior 46.6 49.3 48.8 47.2 45.5 Scale 0-100. Estimated mean scores which vary significantly on a regional level are demarcated in bold. Figure 3 Margins plots visualizing the estimated mean scores for the five regions and their 95% confidence intervals (CIs) based on the best fitted generalized linear models (A) Good feeding, (B) Good housing, (C) Good health, and (D) Appropriate housing, as described in Table 3. The regions are labeled as follows: T, Trondelag, 43 herds; OS, Ostlandet South, 38 herds; ON, Ostlandet North, 29 herds; VS, Vestlandet South, 24 herds; VN, Vestlandet North, 21 herds. 4. Discussion 4.1. Overall status Our objective was to report the status of animal welfare in Norwegian loose-housed dairy herds based on assessments made using the WQ(r) protocol. Just over half of the herds were classified as "Enhanced", the second highest ranking within the WQ(r) assessment framework. The absence of any herds classified as "Excellent" is similar to the findings of other European studies (11, 36-38). Only two herds were categorized as "Unclassified", the lowest ranking. These herds had relatively low scores for the criterion absence of prolonged hunger and very low scores for the criterion absence of prolonged thirst compared to the other herds assessed. These features, higher proportions of very lean cows and water access defined by WQ(r) as insufficient, were consistent with herds classified as "Unclassified" in a study in the Netherlands (36). That study demonstrated that improving water provision was the most effective way for lower ranking herds to move into a higher category while improvements in other aspects did little to improve the overall classification. The authors of that study highlighted that the WQ(r) categories are overly influenced by certain measures, in particular water provision, and poorly sensitive for other measures, such as those contributing to good health. They suggested that this over sensitivity in one aspect, combined with a lack of sensitivity in other aspects, may lead to increased focus on areas that improve the category of the herd at the expense of diverting attentions away from other important welfare issues (36). Even so, herds categorized as "Unclassified" are likely to be experiencing several important welfare issues in addition to insufficient water provision. It is important to acknowledge that the herds assessed may not be wholly representative of the target population of Norwegian loose-housed dairy herds due to the exclusion of herds in the two most northern counties, herds that are not members of TINE and the NDHRS, and herds that were outside of the criteria for herd size. Participation bias, an acknowledged limitation in research where participants take part of their own free will (39, 40), is another limitation of this study. Our findings are potentially biased toward those with an active awareness of, and an interest in, animal welfare. Simultaneously, those who wish to hide what they perceive to be poor animal welfare can do so. Unfortunately, we were limited in our ability to avoid participation bias in our study as only willing participants could be included. Throughout this discussion, comparisons will be made between the results of this study and those from previous Norwegian studies or studies from other countries. The authors acknowledge that these comparisons must be interpreted cautiously due to methodological differences. We are, however, of the opinion that the context they provide is still of value, particularly where the application of the WQ(r) protocol has been consistent. 4.2. Encouraging findings On the criteria level, there were several examples of potential welfare issues being well controlled. These included the absence of prolonged hunger, absence of pain due to management procedures, and good human-animal relationship. These three criteria were particularly highly scored in Norway. The prevalence of very lean animals was higher in this study than has previously been reported in Norway (17). The previous findings were recorded at first insemination which may cause the cows most at risk of low body condition to be under-represented due to acyclicity or management decisions (41). The average proportion of cows classified as very lean was lower in this study than has been seen in studies from other countries (11, 36, 38). From a welfare perspective, a body condition score classified as very lean by WQ(r) is universally unacceptable for any cow at any stage of lactation (10). The cows assessed using the avoidance distance test were, by and large, trustful of humans. Similar results have been seen in Austrian dairy herds (42). The assessors were able to approach the vast majority of cows closer than 50 cm before they withdrew, reflective of a good human-animal relationship in a majority of the dairy herds. Cows' relationship to humans is defined as their perception of humans based on their previous interactions. In addition to genetics, a good human-animal relationship is the result of appropriate behavior by stockpeople and infrequent unpleasant interactions between humans and animals. The presence of positive experiences and absence of negative experiences allows cows to develop trust and confidence in humans (43). A positive relationship between dairy cows and humans has been linked to increased cow productivity and safety in the farm working environment (43-45). 4.3. Welfare challenges Based on the WQ(r) criteria scores, the biggest welfare challenges in Norwegian dairy herds were clinical signs of disease, injuries, compromised resting comfort, and limited time at pasture. Absence of disease scored the lowest on average of all criteria and could be seen as the biggest welfare challenge from a WQ(r) perspective. This is surprising as the health status of Norwegian cattle is generally considered to be high. Norway is free from several endemic infectious diseases of cattle such as tuberculosis, paratuberculosis, bovine viral diarrheoa, and infectious bovine rhinotracheitis. A concerted effort by the Norwegian dairy industry over the last 30 years has led to a reduction of more than 50% for several of the most common disease issues in dairy cows (46). As a result, Norway's antibiotic usage per unit biomass is among the lowest for animal agriculture in the world (47). In particular, the number of mastitis treatments has decreased markedly, with a 60% reduction achieved between 1994 and 2007. During the same period, bulk milk SCC more than halved (15). The trend has continued, with further decreases in the geometric mean somatic cell count in bulk tank milk and reported incidences of clinical mastitis occurring between 2009 and 2020 (21). These improvements have been attributed to accurate record keeping, improved breeding, increased preventive work (including disease specific control programs) and changing attitudes (15, 46). Despite these improvements, the national average score for the somatic cell count measure applied was still classified as problematic by WQ(r). The mean herd prevalence of ocular discharge, another disease-related measure, surpassed the alarm threshold. Ocular discharge is used in combination with nasal discharge, coughing, and hampered respiration to assess the respiratory health of the herd (10). The mean value for nasal discharge surpassed the WQ(r) warning threshold but the mean scores for coughing and hampered respiration were well below their respective warning thresholds. The distinctly seasonal pattern of the prevalences of ocular and nasal discharge suggests that they may be the result of seasonal allergic rhinitis rather than viral or bacterial respiratory illnesses. Although seasonal allergic rhinitis has been little studied in cattle it has been reported (48, 49). This seasonal pattern was seen in a previous study of dairy cows using the WQ(r) protocol (38). It is clear that these potential clinical signs of disease, as assessed by the WQ(r) protocol, remain a challenge in Norwegian dairy herds. The Norwegian dairy industry can take encouragement from the improvements they have made but they cannot afford to become complacent. Sustained efforts are required to maintain and improve the health status of Norwegian dairy cattle and thereby their welfare. It is important to differentiate between the clinical measures used to assess disease in the WQ(r) protocol, which assess the clinical signs of disease, and confirmed instances of disease. If, as we suspect, the high prevalence of ocular discharge is caused by irritating seasonal rhinitis rather than potentially fatal pathogens then it is necessary to interpret that measure with caution. Similarly, as SCC is a measure of both sub-clinical and clinical mastitis, the welfare implications of the SCC results are not fully clear. Furthermore, as mentioned previously, the WQ(r) assessment has been found to be poorly sensitive for improvements in these disease-related measures (36) and this aspect of the WQ(r) protocol is under review. Along with the criterion absence of disease, the criterion absence of injuries was low scoring with respect to the national average. Injuries are of concern for cow welfare as they are associated with pain. Lameness appears to be decreasing in loose-housed Norwegian dairy herds (16) but unfortunately the same cannot be said of integument alterations. Changes to the integument, most commonly of the tarsal, carpal, and neck regions were the most frequently encountered welfare issue in this study with almost four out of every five individuals affected on average. Alarmingly, the prevalence of integument alterations has remained stable over the past 13 years. In 2009, the prevalence of integument alterations was reported as 60.5% and 35.3% for the tarsal and carpal areas, respectively (14). We observed prevalences of 59.3 and 35.6% for the same issues using a similar scoring system. This suggests that they remain a challenge in Norwegian loose-housed dairy herds. The newly established National Animal Welfare Program for Cattle (50) includes a measurement of integument alterations, indicating that awareness of the issue is increasing and that improvement may be forthcoming. Prior to this the only national requirement related to the issue was a vague legislative requirement for dairy cows to have access to a soft, solid lying area (19). Previous research in Norway suggests that this requirement was not always met and failure to do so was a risk factor for integument alterations (14). Moreover, despite rubber cubicle mattresses being considered "soft", integument alterations of the tarsus have been found to be more prevalent, numerous, and severe in herds using mattresses (51). Rubber cubicle mattresses were used in all 155 herds. Additionally, skin alterations are an indicator of dysfunctional housing (14). Discomfort caused by challenges in the environment are also represented by the measure "mean time to lie down". This is an integrative, animal-based measure of the interaction between all cubicle characteristics and the body dimensions of the cows (52). It is therefore an indicator of the suitability of the cows' resting environment. Discouragingly, this is higher compared to other studies (10, 11). Furthermore, nearly one in every ten herds were classified as having a severe problem with collisions during lying down movements. Such findings are consistent with prior evidence that resting comfort is more of an issue in cubicle herds as poorly designed, inadequately adjusted, and uncomfortably bedded cubicles can restrain cows during lying down movements and cause injuries (11). Another management factor associated with integument alterations is the number of days per year spent at pasture. More time spent inside has previously been linked to increased integument alternations (53, 54). In almost entirely pasture-based systems the prevalence of integument alterations is far lower. One study of pasture-based dairy cows in Australia recorded that 86% of herds had no cows with any hairless patches, compared with 0% in this study. The same study found that 56% of herds had no cows with observed lesions, compared with < 1% in this study (53). There is a statutory requirement for cows to have pasture access for at least 8 weeks of the year (19). Based on the results of this study, this requirement is generally met. Despite this, it appears that Norwegian dairy cows spend less time outside than in other countries. For example, the median number of days at pasture per year in this study was little over half the median number of 299 days observed in France (11). Pasture access is limited by the prevailing weather conditions for much of the year and a lack of high-quality pasture in mountainous areas. It could be that despite having some pasture access, the duration is not long enough to reduce the prevalence of integument alterations. A study investigating daily grazing time as a risk factor for tarsal integument alterations found that reductions in the log-odds for lesions and swellings on the tarsus joint were only present in the group which spent the most time per day outside (54). It is possible that there is a type of dose-response relationship between duration of pasture access and the occurrence and severity of integument alterations. The case may be that the effective "dose" of days at pasture is not consistently met under Norwegian conditions. 4.4. Regional variation We hypothesized that the welfare status may vary regionally. Regional variation, if present, would be an important consideration when attempting to investigate the welfare status of a large, geographically diverse country like Norway. A regionally variable welfare status would also have implications for the implementation of region-specific welfare interventions or advisory strategies. The relationship between region and welfare is complex because, as a variable, it is the summary of all of the different observed and unobserved characteristics of said region. We stratified the observed results using GLM to investigate if the sum of these regional factors can influence the welfare status of regions to the extent that they differ significantly from one another. A significant regional difference was found between two regions for only one for the principles, A. Good housing. The variation, while significant, was small. The possibility for variation between Trondelag and Vestlandet North exists in measures related to the criterion comfort around resting as this was the only criterion which could vary between the regions. The associated measures were those of the indoor environment: cleanliness and the interactions between the cows and their resting facilities. Variation in the indoor environment was one of our hypothesized sources of variation between regions prior to the data collection. Unfortunately, due to the complex nature of the issues measured and a lack of specific information about the housing in these regions, it is not possible at this point to identify the cause(s) of the variation between Trondelag and Vestlandet North. We found no regional variation within Norway for the other three WQ(r) principles. Regardless of whether the typical feed composition varies regionally, as we supposed, or not, it appears to meet the cows' nutritive requirements in most cases. We also assumed that the number of days per year at pasture would vary from region to region, but this assumption appears to be incorrect based on these data. The lack of variation on a regional basis, with one borderline exception, runs counter to our initial belief that welfare status would vary markedly from region to region. It has previously been suggested that when cows are kept in similar systems, their welfare is broadly similar from country to country (11). In this study, all herds were cubicle housed for most of the year with pasture access in summer. It may be that the same applies when cows are keep in similar systems intra-nationally. A general absence of regional variation highlights the importance of variation from herd to herd. As mentioned in the results section, variability was present throughout the WQ(r) scores (Table 4) and the prevalences/measures of common welfare issues (Table 5). The principle good feeding and its contributory criteria and measures showed particular high variability. As the variations in this data are not generally present at a regional level, they must instead be at a herd level. The role of the stockperson has been identified as an important determinant of the welfare at a herd level (55, 56). 4.5. Other causes of variation To investigate the presence or absence of regional variations we were required to build generalized linear models, as described. In doing so we identified a number of factors which interacted with potential region effects. In a country as large as Norway there was a necessity for multiple assessors. The WQ(r) protocol was designed with intra-observer reliability in mind (10), however limitations have been identified previously in both dairy and pig herds (57-59). Even though steps were taken during training to ensure the reliability of the assessors' readings, a significant assessor effect was detected during univariable screening for three of the four models. Inter-observer reliability can be increased by more intensive training procedures, as has been demonstrated by lameness scoring (60). Unfortunately, it was not feasible to extend the training due to the limitations on physical meetings in place during the critical training period for this study. Assessor effects could act as confounders for regional effects because the visits performed by each assessor were not evenly distributed across the five regions: Assessor was therefore included as a fixed effect in all four models (A-D). Herd size has been investigated previously for its effect on welfare parameters (38, 53, 61). A statistically significant positive relationship between herd size and the principle score for good housing was detected during univariable screening. In the authors' experience, this positive association is biologically plausible under Norwegian conditions as larger herds are more likely to be housed in more modern housing facilities. Newer housing solutions are conceivably more appropriately designed for modern dairy cows than older housing designs. Cows in larger herds may therefore experience more comfortable conditions, as demonstrated in the data by the positive linear association between herd size and principle score for good housing. Additionally, a curvilinear relationship between herd size and two measures which contribute to the good housing score has been shown in previous research on loose-housed dairy cows (38). Herd size was therefore included as an independent variable in model C. Good housing. By including a binary variable indicating either passive or active recruitment during the univariable screening, we detected a significant positive effect of being passively recruited on the principles C. Good health and D. Appropriate behavior. In short, those who proactively volunteered their participation appeared to score significantly higher, on average, for those two principles (while also accounting for other factors such as region and assessor). Recruitment method was therefore retained in the best fitted models for those principles in order to account for the participation bias potentially identified. 5. Conclusion Our assessments using the WQ(r) protocol provided an approach to reporting the national status of animal welfare in loose-housed Norwegian dairy herds. The status both presented encouraging findings and identified welfare challenges. Particularly positive were the low herd prevalences of very lean cows and the positive relationship between stockpeople and their cattle. The challenges of most concern were injuries arising from conflicts between the cows and their environments, clinical signs such as ocular discharge, and inadequate resting comfort. Our investigation revealed significant regional variation between just two regions in only one of the four principle scores assessed. The suggestion is that contrary to our initial belief, the welfare status at WQ(r) principle level in Norwegian loose-housed herds did not vary on a regional basis in most cases. However, variations in dairy cow welfare were clearly present at a herd level. We conclude, therefore, that attempts to improve dairy cow welfare should be directed at individual herds rather than at a regional level. The welfare of dairy cows is multidimensional and positive achievements in some respects may not compensate for deficiencies in other areas. Stakeholders in Norwegian dairy production should focus on herd-specific opportunities to improve animal welfare. Data availability statement The datasets presented in this article are not readily available because of the need to maintain participant anonymity. Requests to access the datasets should be directed to CB, [email protected]. Ethics statement Animal ethics approval was not required as this was an observational study which did not influence the animal's normal way of life or cause anything other than an entirely temporary light pain or discomfort. This is in line with Section 4.7 of the Norwegian University of Life Science's Ethical Guidelines. Written informed consent was obtained from the owners of the participating herds for the participation of their animals in this study. This study complied with the requirements for data protection and written, informed consent in studies involving human participants described in Section 4.6 of the Norwegian University of Life Sciences' Ethical Guidelines. Written informed consent was obtained from all human participants for their participation in this study. Independent evaluation by the Regional Committee for Medical and Health Research Ethics was considered to not be applicable due to the absence of ethical concerns regarding human participation in this study. Author contributions Conceptualization, study planning, and writing--review and editing: CB, KE-D, RG, SG, CW, and CK. Assessor training: CW. Data collection: CB, KE-D, RG, SG, and CK. Software, data analysis, visualization, and writing--original draft: CB, KE-D, and CK. All authors contributed to the article and approved the submitted version. The authors gratefully acknowledge the farmers who voluntarily participated in this study. Conflict of interest TINE SA, a minority financial contributor to the WelCow project, of which is this study is a part, and the employer of two coauthors (RG and SG), has a commercial interest in the Norwegian dairy industry. TINE SA did not, by contractual agreement, have any influence over the content or nature of this publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References 1. Welfare Quality(r). Assessment Protocol for Cattle. Welfare Quality(r) Network (2009). 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PMC10000293 | Front Psychol Front Psychol Front. Psychol. Frontiers in Psychology 1664-1078 Frontiers Media S.A. 10.3389/fpsyg.2023.1102085 Psychology Original Research New exploration of creativity: Cross-validation analysis of the factors influencing multiteam digital creativity in the transition phase Chen Weilong 1 Wang Baohua 1 * Chen Yi 1 Zhang Jing 2 Xiao Yuchun 2 1Zhejiang Institute of Social Governance and Communication Innovation, Communication University of Zhejiang, Hangzhou, China 2School of Business Administration, Zhejiang Gongshang University, Hangzhou, China Edited by: Silvio Manuel da Rocha Brito, Instituto Politecnico de Tomar (IPT), Portugal Reviewed by: Daniela Blettner, Simon Fraser University, Canada; Francisco Manuel Morales Rodriguez, University of Granada, Spain *Correspondence: Baohua Wang, [email protected] This article was submitted to Organizational Psychology, a section of the journal Frontiers in Psychology 24 2 2023 2023 14 110208518 11 2022 06 2 2023 Copyright (c) 2023 Chen, Wang, Chen, Zhang and Xiao. 2023 Chen, Wang, Chen, Zhang and Xiao This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Multiteam digital creativity (MTDC) is a new domain of creativity study that fits the new developments of the digital era, thus scholars have called for exploring MTDC in the fine-graining phase. This paper responds to this call, and adopts two studies and cross-validation analysis to explore the theoretical framework of the impact factors of MTDC in the transition phase. Study 1 adopts the qualitative analysis method of rooted theory to explore a more comprehensive impact factor and to maximize the new theory's saturation. Study 2 adopts the CL-WG DEMATEL method, one analysis method of group decision-making and optimized concept lattice, which could cross-validation analyze the results of Study 1 and further determine the importance of the factors. The results of the studies indicate that the influencing factors of MTDC are multilevel, and the factors such as the organizational digital climate, team psychological empowerment, individual digital cognition and emotion, and leadership competence have greater impacts on MTDC. This indicates that the transition phase has a unique internal mechanism. This paper constructs a theoretical framework of factors influencing MTDC in the transition phase and provides new theoretical and practical references for how organizations could fully stimulate MTDC in the digital era. In addition, the cross-validated analytical method further enriches the study tools in the domain of organizational behavior. cross-validation analysis digital creativity influencing factors MTS theory transition phase Zhejiang Provincial Philosophy and Social Sciences Planning Project23NDJC031Z Zhejiang Province Soft Science Research Plan Project of China2022C35072 Humanity and Social Science Foundation of Ministry of Education of China21YJCZH213 National Natural Science Foundation of China 10.13039/501100001809 72074195 pmcIntroduction Digital technology has led to significant changes in the organizational environment and brought us into the digital era (Yoo et al., 2010; Grover et al., 2022). Digital technology differs from previous virtual network technologies in its transferability, flexibility and editability, most organizations are eager to embrace digitalization to gain a new competitive advantage (Shao et al., 2021). Creativity is also one of the most needed competitiveness in the digital era (Van Rensburg et al., 2021). Digital creativity, a new cross-domain of digital technology and creativity, is important competitiveness in the digital age (Lee and Chen, 2015). Digital creativity refers to various forms of creativity based on the digital foundation or driven by digital technology (Shao et al., 2021; Van Rensburg et al., 2021). However, the study on digital creativity in the domain of organization is relatively limited, so some scholars call for more relevant research (Shao et al., 2021; Zhang et al., 2022). The iterative development of digital technology and knowledge further drives the prevalence of the multiteam working model (Rapp and Mathieu, 2019; van de Brake et al., 2020). Multiteam working models can enhance an organization's ability to innovate and adapt effectively to dynamic and complex organizational environments (De Vries et al., 2016; Luciano et al., 2020). Thus, scholars have called for more attention to organizational issues from a multi-team perspective (Lei et al., 2022; Wu et al., 2022). The multiteam system (MTS) theory provides a reference theory for organizations' multiteam working models. MTS is an interdependent system of multiple teams interacting to achieve a set of subgoals guided by a common goal (Mathieu et al., 2001), which has gradually become a hot topic (Luciano et al., 2018; Zaccaro et al., 2020). Based on the above digital creativity and MTS theory, multiteam digital creativity (MTDC) is defined as the generation of novel and practical ideas, services, and processes, driven by digital technologies or digital environments, which is a hybrid of multi-level creativity synergy (Zhang et al., 2022). MTS theory proposes that the multiteam collaboration process comprises the transition phase and action phase, which is called the performance episode (Marks et al., 2001; Mathieu and Schulze, 2006). The transition phase focuses on multiteam evaluation and planning activities, including task analysis, goal setting and strategy development, to guide the teams toward multiteam goals; and the action phase focuses on multiteam goals and systematic monitoring, mutual support among teams, shared feedback and mutual synergy to ensure the achievement of organizational goals. Different phases have unique characteristics (Torres et al., 2021). Thus, targeted research should be adopted for different phases. This paper focuses on the transition phase. Specifically, this paper explores the influencing factors of multiteam digital creativity in the transition phase. Previous studies on factors influencing digital creativity have been piecemeal. E.g., the exploration of creativity influencing factors based on virtual design teams (Chamakiotis et al., 2013), the study of digital creativity themes and framework based on literature compilation (Lee and Chen, 2015). The model of factors influencing MTDC in the transition phase is a new domain. Thus, this paper adopts two interactive validated exploratory research methods to enhance the reliability of theoretical exploration. Study 1 adopts the qualitative analysis method-rooted theory. This method is capable of effectively discovering the impact factors of new theories through multilevel coding. Therefore, this is an exploratory method to explore a more comprehensive impact factor and to maximize the saturation of new theories (Hoda et al., 2012). Study 2 adopts the conceptual lattice-weighted group DEMATEL analysis method (CL-WG DEMATEL method), which is a quantitative measure that considers the opinions of the expert group, the proportion of expert weights and the degree of interaction between influencing factors (Shi et al., 2016). This method uses group decision-making and optimized concept lattice, which allows cross-validation of the results of Study 1 and further analysis of the importance of the impact factors. Thus, this is an effective research method to further increase the credibility of the new theory exploration. Both methods are exploratory tools based on a cognitive perspective, which can be cross-verified, and is confirmed to make more comprehensive and accurate decisions on influencing factors (Xiao and Zhang, 2020; Zhang et al., 2022). Overall, this paper has some contributions. First, this study constructs a new theoretical framework of the impact factors of MTDC in the transition phase, which provides future research for digital creativity, and a practical guide for organizations to stimulate digital creativity. Second, this paper adopts two cross-validated research methods to explore the new theoretical framework, which further enriches the research tools in the field of the organization. Third, this paper studies MTDC specifically for the transition phase, further fine-graining MTS theoretical research while making it easier for organizations to provide more targeted practical references for the special phase. Finally, through the CL-WG DEMATEL method, this paper finds that the factors affecting MTDC are unique, and the importance of various factors is different. In addition, this paper responds to the theoretical call and enriches MTS and creativity theory. Literature review Multiteam system theory The multiteam system refers to a system consisting of two or more teams interacting to achieve a set of goals. In such a system, the subteams within the system have their own proximal goals but interact under a common vision; and there is interdependence between the subteams, at least in terms of inputs, processes or outputs (Mathieu Mathieu et al., 2001). MTS theory is a development of the team behavior process theory (Marks et al., 2001). MTS theory states that the multiteam behavior process is similar to the team process and includes two different behavior phases, called the transition phase and the action phase (Mathieu and Schulze, 2006). As in the introduction above, the two phases have different concerns. Therefore, it would be meaningful to focus on one specific phase (Torres et al., 2021). This paper responds to the theoretical call and focuses only on the transition phase to further fine-graining MTS theoretical research. More and more organizations are focusing on multiteam working models, and scholars are also paying more attention to MTS theory from multiple perspectives, such as multiteam collaboration (Davison et al., 2012), leadership (DeChurch and Marks, 2006), cross-border identity (Cuijpers et al., 2016), behavioral processes (Van den Berg et al., 2014), and cognition and motivation (Lanaj et al., 2013). An experimental study found that the coordinated actions developed by unit team boundary managers and system leaders had a positive impact on outcomes only when collaboration revolved around the team's most critical tasks (Davison et al., 2012). One study found that multiteam identity influences multiteam output after mediation through team conflict (Cuijpers et al., 2016). Furthermore, the social identity of multiteam systems will have negative effects in task complexity situations due to more individual dissipation (Porck et al., 2019). One overview stated that important influences on multiteam effectiveness include coordination processes; leadership structure; cognitive, affective, and motivational emergent states; MTS boundary states (internal or external); and team variability (geographic, functional, cultural, and normative; Zaccaro et al., 2020). One paper proposed that diversity and dynamism were the two key structural features of MTS; and the key factors influencing MTS outcomes included belonging needs, cognitive abilities, and affective states (Luciano et al., 2018). Overall, the factors influencing the output of multiteam are diverse and complex. Creativity and digital creativity Creativity is defined as the generation of ideas, products, processes, and services that are novel and useful to individuals or teams (Amabile et al., 1996). Creativity also is the result of the interaction between an individual and the organizational environment (Woodman et al., 1993). From a systematic view, creativity includes the "4Ps" elements, called the individual creator (person), the creative process (process), the individual creator (person), the creative process (process), the creative product (product), and the creative environment (place; Runco and Kim, 2013). In the digital era, there are increasingly more "digital natives," and digital innovation is a hot topic. However, there is relatively little research on digital creativity. Some previous studies explored creativity based on an Internet perspective, such as focusing on the factors influencing creativity in virtual design teams (Chamakiotis et al., 2013), and exploring the incentives and impediments to creativity in virtual teams based on rooting theory (Ocker, 2005). However, digital technology is both similar to and different from the earlier networked virtuality. As stated above, digital technologies possess transferability, flexibility and editability (Shao et al., 2021). Digital creativity is a new way to explore creativity and showcase creativity using digital tools and technologies, is becoming an important skill in the workplace(Van Rensburg et al., 2021), and is an important part of people's daily lives in the digital era; thus, organizations should pay high attention to digital creativity (Perez-Fuentes et al., 2019). Digital creativity is creativity inspired by the use of digital tools and technologies (Shao et al., 2021; Van Rensburg et al., 2021). Lee and Chen (2015) define digital creativity as the diverse creativity of an individual, team or organization driven by digital technology and the ability of people to demonstrate novelty and usefulness in a variety of innovative activities using digital technology or through digital technology products. According to the literature review, digital creativity is a special form of creativity that emphasizes the formation of novel and practical ideas based on a digital environment or driven by digital technology (Amabile et al., 1996; Lee and Chen, 2015; Van Rensburg et al., 2021). Multiteam digital creativity and influencing factors From the MTS perspective, the study of MTDC is a new paradigm in creativity theory research. Woodman et al. (1993) proposed the theory of creativity interactions among individuals, teams, and organizations that provides a hybrid cross-level perspective on creativity theory. Drawing on MTS theory and creativity theory, this paper proposes the concept of MTDC. Unlike traditional creativity, MTDC has three distinctive features: (1) it is an interdependent multiteam system that interacts to achieve a set of subgoals guided by a common vision, whereas creativity is the result of hybrid interactions and is more systematic, dynamic, and complex; (2) it emphasizes a digital environment or is driven by digital technology; and (3) it is novel and practical in the formation of ideas (Amabile et al., 1996; Zhang et al., 2022). The factors influencing creativity are diverse and complex. The creativity component model proposes that the three important structural elements of creativity are the following: expertise, creative skills, and intrinsic motivation (Amabile, 1988). The interaction model of creativity suggests that creativity is the result of the interaction of multilevel factors such as individual cognition and emotion, team norms and team motivation, organizational culture and organizational resources, and other factors (Woodman et al., 1993). This multi-level research framework provides good inspiration for the follow-up study of influencing factors. Studies on the factors influencing digital creativity are relatively limited. Research through rooting theory has found that significant enhancers of creativity in virtual teams include the existence of a variety of social influences, a collaborative team climate, stimulating colleagues, etc. (Ocker, 2005). Inhibiting factors that affect creativity in virtual teams include technical difficulties, lack of shared understanding, time pressure, domain knowledge, etc. (Ocker, 2005). E-leadership, trust, subgrouping, conflict and diversity may be the key to solving the problem (Chamakiotis et al., 2013). Through empirical studies, some scholars have confirmed that digital creativity is positively correlated with digital inclination, the digital environment, and the professional field (Lee D. S. et al., 2013), also influenced by authentic leadership, sharing team climate, psychological empowerment, and information sharing (Hahm, 2017). Others find that technology digital affordance, digital knowledge, and task variety affect digital creativity (Shao et al., 2021). The literature review also revealed that factors influencing digital creativity include human, technological, environmental, creative arts, learning, and policy (Lee and Chen, 2015). Some scholars have also proposed that the factors influencing digital creativity are multi-layered, including individuals, teams, and organizations (Lee D. S. et al., 2013). Multi-level influencing factors may also include individuals, technology, teams, and organizations (Chamakiotis et al., 2013). Zhang et al. (2022) initially explored the influencing factors of MTDC in the action phase, and further called for a deeper exploration of MTDC influencing factors from the transition phase. In general, there have been more studies on individual or team creativity, and relatively few on digital creativity. However, research on digital creativity from an MTS perspective is limited. Multiple teams are an important and common organizational structure (Mell et al., 2020; Zaccaro et al., 2020). To bridge this gap, this paper explores the factors influencing MTDC in the transition phase from the perspective of MTS theory. Two studies engaging in cross-validation exploratory research, each using a different method (Study 1 and 2), systematically investigate the frame of the factors influencing MTDC in the transition phase. Study 1: Identification of the influencing factors Method Study 1 adopts the qualitative analysis method, which focuses on conceptualization and theory scope (Urquhart et al., 2010), which can effectively uncover new influences on the theory (Mello and Flint, 2009; Hoda et al., 2012). This study adopts video or face-to-face interviews and questionnaires. The process of selecting interviewees is based mainly on the matching principle to ensure sample representativeness and theoretical saturation (Zhang et al., 2022). Participants and procedure To increase the representativeness of the semistructured interviewees, this paper adopted three main steps. First, 15 managers from four high-tech enterprises in which digital technology had been deeply embedded were selected as the preliminary interviewees, then asked to recommend additional 55 multiteam managers. They have a more in-depth understanding of MTDC. Second, based on the definition of MTS and the transition phase in the performance episode (Mathieu and Schulze, 2006), investigators fully communicated with the interviewees about the relevant concepts so they can deeply understand the research semantics of MTS and identify operational definitions and fitness criteria. First, the selected object should be to manage two or more different teams with one or more common goals, and each team has strong interdependence in at least one aspect, which conforms to the characteristics of the multiteam. In addition, in the transition phase, the core control standard is the preparation of at least one multiteam common plan and the assignment of tasks to two or more teams. Finally, based on the preliminary interview results, 35 managers who met the criteria were selected for at least 1 h of interviews. The basic information of the interviewees shows in Table 1. The following topics were interviewed. What are the multiteam composition structures and characteristics? How does digital creativity arise? What is the specific performance of the company in terms of digital creativity or digital innovation in the transition phase? What factors generate or hinder digital creativity? Discuss the specific performance of MTDC in your organization and other aspects. Table 1 The basic information of the interviewees. Category Content Frequency Percentage (%) Gender Male 22 62.86 Female 13 37.14 Education Bachelor's or below 16 45.71 Graduate or above 19 54.29 Age 35 or below 21 60 35 or above 14 40 Analysis According to the procedure, the coding includes excerpting, coding, and categorizing, then forms three levels of coding based on the analysis and categorization (Glaser, 1978). First-level coding Based on the data collected, three study team members completed the excerpting, coding, and categorizing. To improve the effectiveness of coding, the team leader first conducted a trial coding and proposed a coding specification, and the other 2 researchers coded separately according to the same specification and checked each other's coding consistency. In addition, those concepts that reached a consensus were put into the initial concept base while those concepts that did not reach a consensus concept were decided collectively. Interviews, questionnaires, and coding were performed in parallel individually. Then, based on the next batch of interviews or questionnaires, invalid concepts were eliminated and clustered to form valid concepts. Statistics were conducted based on the coding, and the valid concepts with the highest mention frequency were screened out and finally summarized into valid codes. Some representative interviews were organized into a coding library, as shown in Table 2. Table 2 Coding database of some interview contents in the transition phase. Effective Concepts Frequency Overview of some of the interviews Digital Cognition 22 Can understand and grasp digital development well and have a clear understanding of the target tasks. Good cognition of multiteam needs Job Embedding 15 In a multiteam system, interdependence is important. Everyone needs to be actively engaged in their work and willing to sacrifice themselves Positive Emotions 18 The individual is enthusiastic, positive, active, alert, full of energy, and able to engage happily in their work Network Resources 26 Rich social resources and access to novel and useful information from multiple sources, especially digital innovation resources Cross-Border Capabilities 12 Leaders are able to coordinate well across multiple teams, especially between digital technology teams and traditional teams Management Skills 16 Ability to choose the right leadership style to manage and motivate everyone Self-Motivation 12 Having a certain time and space allows individuals to combine work and interests to explore new things Sense of Responsibility 24 Have a strong sense of responsibility and strive to find ways to identify and solve problems Team Belonging 17 Identify very much with your team, individuals are an important part of the team, and team goals are very meaningful Task Conflict 19 When setting goals, assigning tasks, or analyzing problems, the group sometimes heatedly discusses and sometimes argues Relationship Conflict 22 There are conflicts in emotional relationships and do not see eye to eye with each other Process Conflict 10 Disagreement on the way to work and the process Diverse Structures 21 Different teams possess their own specialized skills, digital competencies and knowledge structures. Better able to adapt to digital Open Structure 13 The team is open to dynamic change. There are multiple participating subjects Digital Structure 11 Having digital high-tech experience in top companies will bring us a more advanced perspective Shared Goals 8 Have one or more of the same goals Task Interdependence 15 The tasks of the various teams are interconnected, with the digital team being particularly important Multiteam Trust 17 The teams trust each other and can work well together Digital Innovation Culture 28 The organization advocates digital innovation, everyone includes each other, and there is a special emphasis on digital development Motivational Mechanism 15 With moderate motivational mechanisms, special attention is given to market needs in the digital field Digital Training 17 Proactively organize digital training and actively guide digital innovation Digital Infrastructure Resources 14 Digital infrastructure is an important support for organizing digital innovation Digital Human Capital 20 The organization is able to provide strong support when people with all skills, especially digital expertise, are needed Platform and Ecological Resources 15 Matching digital platforms and ecosystems are very important. If you do not proactively integrate you will miss the windfall of the moment Second-level coding This process focused on reclustering the valid concepts formed in the first-level codes. First, the study team clustered the valid concepts into different categories to form a preliminary second-level coding library. Second, six experts in organizational behavior and human resources were invited to analyze the codes. Through interview induction, theoretical reference, and expert opinions, the codes were clustered into eight primary categories. Table 3 shows some concepts of the second-level codes. Table 3 Main category library of the second-level coding in the transition phase. Main Categories Effective Concepts Main Category Connotations Digital Cognition and Emotion Digital Cognition Have a clear understanding of the organization's digital strategic goals and be fully engaged in their work Job Embedding Positive Emotions Leadership Competence Network Resources Leadership's management style, resources and capabilities promote creativity Cross-Border Capabilities Management Skills Team Conflict Task Conflict A perceptual process arising from differences or dissonance in goals, perceptions, and visions among team members, classified as task conflict (TC), relationship conflict (RC), and process conflict (PC; Jehn and Mannix, 2001) Relationship Conflict Process Conflict Team Psychological Empowerment Self-Motivation The psychological perception of being empowered, as experienced collectively by team members, is an intrinsic and continuous work motivator that enhances an organization's performance (Rosen, 1999; Chen et al., 2022) Sense of Responsibility Team Belonging Multiteam Structure Diverse Structures The multiteam components, including the structures of diversity, openness and dynamic adaptability Open Structure Digital Structure Multi-Team Orientation Shared Goals Guided by shared goals and task interdependence, teams relate to each other with trust and eventually develop a complementary multiteam orientation (Wijnmaalen et al., 2019) Task Interdependence Multi-Team Trust Organizational Digital Climate Digital Innovation Culture Multiteam members' perception of an organization's supportive climate and the organization's stimulation of members' creativity Motivational Mechanism Digital Training Digital Resource Matching Digital Infrastructure Resources The digital infrastructure, digital platforms, and ecosystems that are available in the organization are the foundation. The combination with human resources is the guarantee of digital creativity Digital Human Capital Platform and Ecological Resources Third-level coding With reference to creativity theory and MTS theory, a theoretical structure frame was established by logically analyzing the 8 s-level master categories. The four key categories of MTDC in the transition phase were mined according to the hierarchical structure at the individual, team, multiteam, and organizational levels. Results Based on the results of the above three-level coding and the MTS theory (Mathieu et al., 2001), this study finds that the frame of the factors influencing MTDC in the transition phase has four levels, specifically the individual level (digital cognition and emotions, leadership competency), team level (team psychological empowerment and team conflict), multiteam level (multiteam structure and multiteam orientation), and organizational level (organizational digital climate and digital resource matching). The four levels of interaction influence the process and outcome of MTDC. As mentioned earlier, the transition phase of the multiteam behavior process has its uniqueness. The frame shows in Figure 1. Figure 1 Frame of the factors influencing MTDC in the transition phase. Based on the frequency aggregation in Table 1 and the main category in Table 2, this paper finds that the individual level's digital cognition and emotion, leadership competence, team psychological empowerment, and organizational digital climate have greater impacts on MTDC in the transition phase. Study 2: Validation and centrality analysis Method This section adopts the optimized DEMATEL analysis method-the conceptual lattice-weighted group DEMATEL method (CL-WG DEMATEL method). The DEMATEL method has been widely used to identify and evaluate complex relationships between influencing factors (Lee H.-S. et al., 2013). But the traditional means suffers from the one-sidedness and limitations of a single expert's opinion. There is heterogeneity among experts in terms of professional experience, educational backgrounds, and value preferences; and the judgment results are frequently different, requiring the formation of reasonable weights for expert judgments. The concept lattice technique, actually a concept hierarchical clustering process that essentially describes the association of objects and attributes and integrates the connotations and extensions between concepts, can effectively obtain the expert weighting ratio (Xiao and Zhang, 2020). The CL-WG DEMATEL method could cross validates the results of Study 1 and further distinguishes the importance of the influencing factors, which is an effective and complementary new theoretical exploration tool (Zhang et al., 2022). Participants and procedure The optimized method is described below. Step 1: Form the muster of impact factors X = {X1, X2, ..., Xn}. Step 2: The comprehensive evaluation forms the direct relationships between the influencing factors. The initialized direct influence matrix is: z=[0Z12Z1JZ210Z2JZi1Zi200] Step 3: Calculate the new direct influence matrix. Industry or university experts in organizational behavior were invited to score. The evaluation results of a certain class of factors are clustered according to p experts. These results are copolymerized into ph classes. s1, s2, ... sph are used to denote the first, second ... and nth type; and the same weight is given to experts in the same category. The hypothesis is as follows: b=i-1psi2, where gi is the expert weight, i-1pgisi2=1, and si=bgi. According to the expert weights, the influence coefficient among the factors is obtained as follows: zij'=i-1pgizij(i,j=1,2,,n). Accordingly, the direct impact matrix after being transformed by the weighting factor is: z=[0Z12'Z1J'Z21'0Z2J'Zi1'Zi2'00] Step 4: Determine the comprehensive impact matrix T. If g=1/max(j=1nZij'), where N = gZ,Then T =limk-(N+N2+NK)=N(1-N)-1 Step 5: According to the integrated impact matrix, calculate the degree of influence, degree affected, degree of centrality, and degree of causation. The degree of influence (ID): fi=i=1ntij(i=1,2,,n) Degree affected (AD): ei=j=1ntji(i=1,2,,n) Degree of centrality (CTD): ri=fi+ei Degree of causation (CSD): zi=fi-ei CTD represents the importance in the set of influencing factors, and CSD represents the correlation with other factors. If Zi is greater than zero, this factor can influence other factors to a greater extent; and if it is less than zero, this factor is more influenced by other factors (Zhang et al., 2022). Analysis According to the steps presented above, the specific data are analyzed as follows. Step 1: The set of impact factors about MTDC was formed: X = {X1, X2, ..., Xn}. Step 2: Six experts in organizational behavior were requested, to judge the direct relationships between the influencing factors. The weights of the judgment include 0 = none, 1 = weak ... and 5 = strong. The partial initialized direct impact matrix is: Z1= Z2= Z3= Step 3: Determine the new direct relationship matrix. For example, experts score the relationship between "digital cognition and emotion" and "leadership competency." According to the clustering results, if the first category is experts 1, 2, 4 and 6 and the second category is experts 3 and 5, then s1 = 4, s2 = 2, g1 = g2 = g4 = g6 =420, g3 = g5 = 220, and Z12'=4x420+4x420+3x220+4x420+3x220+420=3.8.The calculations of the other influencing factor relationship values are similar. The new direct relationship matrix is as: Z=[03.84.04.22.53.54.043.84.5044.212.644.2143.54.573.504.042.83.5742.333.833.83.92032.23.83.063.53.53.214.503.5332.53.362.83.53.2103.2133.793.213.7944.5404.213.43443.363.793.540] Step 4: Calculate the normalized direct relationship matrix N (g=1/27.5). N=[00.13820.163600.15270.15270.14550.15320.16620.12730.13940.138200.14690.142700.09090.12730.09610.15320.14690.13820.14550.12730.10180.12990.10910.08000.14550.08480.13820.11110.12730.12730.09090.12210.11690.16360.10180.12730.13770.11690.12470.14550.13770.14550.14550.122100.12730.116900.10910.10910.11690.09090.16360.14550.13770.127300.15320.14550] And the integrated impact matrix T is: T=[1.27781.35231.45891.27011.40061.47731.43511.52081.36541.29011.30231.25681.21281.41561.29511.24151.19321.31001.23221.36851.40181.23391.44111.26091.15281.26011.12081.18051.34511.14441.29641.12711.30331.26051.13851.12471.28611.39541.13851.22381.45331.39001.38951.35871.44341.53151.39521.45551.03281.22781.02040.98841.28501.13501.15501.00211.29981.37671.23131.31211.32811.29411.40081.1133] Results According to the integrated impact matrix, calculate the degree of influence, degree affected, degree of centrality and degree of causation. The specific results for each degree show in Table 4, sorted by CTD. Table 4 The results of each degree in the transition phase. Influence Factor ID AD CTD CSD Order Digital Cognition and Emotion 10.6471 10.6890 21.3360 -0.0419 2 Leadership Competency 10.9877 10.3032 21.2909 0.6845 3 Team Conflict 10.1864 10.6069 20.7933 -0.4205 5 Team Psychological Empowerment 9.8205 11.2615 21.0820 -1.4409 4 Multiteam Structure 9.9258 9.2832 19.2090 0.6426 7 Multiteam Orientation 8.7914 10.0243 18.8156 -1.2329 8 Organizational Digital Climate 11.1168 10.6534 21.7701 0.4634 1 Digital Resource Matching 10.6565 9.3109 19.9674 1.3457 6 Referring to the ranking of CTD, this paper finds that the individual digital cognition and emotion, leadership competence, team psychological empowerment, and organizational digital climate are the preceding influencing factors in the transition phase, and are distributed in three levels. The cross-validation results of study 2 show consistency with study 1. Discussion and conclusion The results of the two studies are consistent, indicating that the cross-validated method has good research reliability. This paper finds that the factors influencing MTDC in the transition phase include multi-level. Our results are similar to one study, which proposed that digital creativity is influenced by multi-level influencing factors, such as individual, team, and the environment (Chamakiotis et al., 2013). Creativity in virtual teams is also similarly influenced by multi-level factors (Ocker, 2005). This indicates that our findings are consistent with the factors influencing creativity (Woodman et al., 1993). However, MTDC has its own uniqueness. MTDC highlights the multiteam level, which is consistent with the prevalence of multi-team working patterns in Internet companies (Zhang et al., 2022). Further analysis through Study 2 reveals that digital cognition and emotion at the individual level, leadership competency at the individual level, team psychological empowerment at the team level, and organizational digital climate at the organizational level are particularly important for MTDC in the transition phase. The difference in the centrality of MTDC in the transition phase is shown in Table 5. However, this study showed that the importance of multiteam-level influencing factors came low. This may be that the transition phase of multiteam systems is in the formation period, they do not know each other or have no consensus, and need to go through further familiarization and bonding (Xiao and Zhang, 2020); therefore, it is difficult to quickly form digital creativity at the multiteam level, which at this time mainly relies on other levels of influence. Table 5 Difference in the centrality of MTDC in the transition phase. Influence factors Action phase Individual Digital Cognition and Emotion Leadership Competency Team Team Conflict Team Psychological Empowerment Multiteam Multiteam Structure Multiteam Orientation Organization Organizational Digital Climate Digital Resource Matching The number "" indicates the centrality ranking of the influencing factors. The more "" the higher the ranking. The results of the study show that organizational digital climate is the maximum degree of centrality in the influencing factors. MTDC relies heavily on the organizational support climate and digital innovation stimulation. Conservative and entrenched organizations are often too hesitant and worried to adapt to the dynamics and complexity of the digital environment. In the digital environment, organizational climate plays an important role in creativity (Jin et al., 2022). A good innovation support climate can provide a solid organizational guarantee for multiteam strategy development and goal analysis while digital training and stimulation can provide multiteam collaboration normality and innovation awareness. The literature review also shows that organizational climate is closely related to digital creativity (Lee and Chen, 2015). Thus, organizations should focus a lot on creating a better organizational digital climate. The second most important is digital cognition and emotion. It means clearly understanding the organization's digital strategic goals and fully engaging in their work. It suggests that individual cognition and emotion are key to stimulating creativity (Ocker, 2005). E.g., individuals who possess a "promotion focus" (Jin et al., 2016), have good digital skills, and are more inclined to digital trends, will further promote creative activities. Individuals with good digital cognition will be able to fully understand the assignment of tasks in the transition phase and maximize their potential. These individual factors are closely related to digital creativity (Lee and Chen, 2015). Thus, stimulating MTDC is closely related to digital cognition and emotion. The results of the study indicate that leadership competency ranks third in centrality. Leadership is a core factor in multi-team systems (DeChurch and Marks, 2006; Zaccaro et al., 2020). The coordination of multiteam boundaries is often the responsibility of team leaders, and the ability of individual leaders to act across boundaries is critical to multiteam (de Vries et al., 2022). In addition, leaders with extensive social network resources can provide richer perspectives on multiteam goal setting and task coordination (Zaccaro et al., 2020). Thus, organizations should develop and select leaders who match. Meanwhile, leaders should actively adapt to the needs of the organization. Finally, the fourth ranking in centrality is team psychological empowerment. This is an intrinsic and continuous work motivator that enhances an organization's intrinsic level of performance (Rosen, 1999; Maynard et al., 2013). One study confirms a positive correlation between psychological empowerment and organizational creativity (Zhang and Bartol, 2010). An empirical study of a large digital technology company found that empowered leaders positively influence psychological empowerment, which in turn influences intrinsic motivation and creative engagement processes (Zhang and Bartol, 2010). Team psychological empowerment can stimulate team creative processes and thus promote multiteam creativity. Implication This paper adopts an interactive validation manner to explore and analyze the factors influencing MTDC of high-tech firms. Study 1 adopts a qualitative analysis method such as the rooting theory to fully explore the influencing factors, and study 2 uses the CL-WG DEMATEL method to further verify and analyze the importance of factors. The two cross-validated research methods further enrich the methodology in the field of the organization. Second, this paper constructs a theoretical framework of MTDC influencing factors in the transition phase. This study indicates that influencing factors of MTDC are multi-levels, consisting of individual, team, multiteam, and organizational levels. In the transition phase, the individual level comprises digital cognition and emotion, and leadership competency, the team level comprises psychological empowerment, and team conflict, the multiteam level comprises the multiteam structure, and the multiteam orientation, the organizational level comprises the organizational digital climate, and digital resource matching. This study responds to the theoretical call of further exploring MTDC and digital creativity (Shao et al., 2021; Zhang et al., 2022), and this paper further enriches the theory of digital creativity and MTDC. Meanwhile, this paper provides a practical reference on how to stimulate MTDC in organizations, fully stimulating MTDC is a multi-level system engineering. Third, further analysis of the results of Study 2 shows that the influencing factors of MTDC have differential centrality. The organizational digital climate, team psychological empowerment, individual digital cognition and emotion, and leadership competency are particularly important for MTDC during the transition phase. As it is obvious, the transition phase has its uniqueness. Thus, organizations should pay more attention to partial influencing factors during the transition phase, especially those with high centrality. This paper provides a theoretical and practical reference for the organization to focus on which critical factors in the transition phase. In the process of implementation, the organization should take different measures according to their importance in the case of limited resources. Finally, the paper finds both differences and similarities between the influencing factors of MTDC and organizational creativity. Although MTDC is a study of creativity, MTDC focuses more on the digital domain (Zhang et al., 2022), such as digital cognition, digital structure, digital innovation culture, digital human capital, platform and ecological resources, and so on. Also, the influencing factors of MTDC include not only individual, team, and organizational levels, but also multiteam level, such as multiteam structure and multiteam orientation. This is not consistent with literature studies on the factors influencing creativity (Woodman et al., 1993), which do not focus on the multiteam level. Thus, in the digital era where multi-team working patterns are increasingly prevalent, organizations should both follow the rules of digital development and conform to the inherent mechanisms of MTS (Zhang et al., 2022). This study responds to the call for further research from the MTS perspective (Lei et al., 2022; Wu et al., 2022) and the transition phase perspective (Zhang et al., 2022), and constructs a specific and systematic frame of the influencing factors of MTDC specifically for the transition phase, which provides a theoretical and practical reference for organizations to conduct precise scientific and rational management and achieve efficient and dynamic creative development. Limitations This paper has some limitations. First, the sample size of this study is relatively small. However, this paper adopts the cross-validation method to justify the results, and the conclusions of the two studies are consistent, which shows that the research results are effective. Previous studies have similarly shown that such a sample size is appropriate in studies like the two cross-validation research approaches (Shi et al., 2016; Xiao and Zhang, 2020; Zhang et al., 2022). For future studies, the sample size could be appropriately expanded to enhance the validity of the study. Second, the interviewees are mainly from companies in China's Yangtze River Delta region. Although the selected companies are at the forefront of digital construction and can better reflect the typical situation of MTDC, the sample is still rather one-sided. For future studies, a wider range of companies and a wider range of countries could be selected to increase the representativeness of the results (Zhang et al., 2022). Third, the results of the interviews are not tested by other various research approaches. This paper adopts the method of grounded theory and the CL-WG DEMATEL method while following the principle of matching theory and data. Future research could adopt more diverse research methods such as the full-cycleresearch approach, or empirical studies with large samples, thus taking advantage of the strengths of various research methods (Chatman and Flynn, 2005). Data availability statement The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s. Author contributions WC and JZ: conceptualization, methodology, writing - review and editing, project administration, and funding acquisition. WC, YC, and JZ: software, formal analysis, investigation, data curation, writing - original draft preparation, and visualization. YX: supervision. WC, JZ, and BW: validation. All authors contributed to the article and approved the submitted version. Funding This paper was supported by the Zhejiang Provincial Philosophy and Social Sciences Planning Project (23NDJC031Z), Zhejiang Province Soft Science Research Plan Project of China (2022C35072), Humanity and Social Science Foundation of Ministry of Education of China (21YJCZH213), National Natural Science Foundation of China (72074195), and National Social Science Foundation of China (20CTQ010). Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Amabile T. M. (1988). 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PMC10000294 | Front Psychiatry Front Psychiatry Front. Psychiatry Frontiers in Psychiatry 1664-0640 Frontiers Media S.A. 10.3389/fpsyt.2023.1111754 Psychiatry Systematic Review Low-frequency repetitive transcranial magnetic stimulation for children and adolescents with first-episode and drug-naive major depressive disorder: A systematic review Zheng Wei 1 * Lan Xian-Jun 2 Qin Zhen-Juan 2 Yang Xin-Hu 1 Shi Zhan-Ming 3 1The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China 2The Brain Hospital of Guangxi Zhuang Autonomous Region, LiuZhou, China 3Chongqing Jiangbei Mental Health Center, Chongqing, China Edited by: Huanzhong Liu, Chaohu Hospital of Anhui Medical University, China Reviewed by: Lei Xia, Chaohu Hospital of Anhui Medical University, China; Chuanjun Zhuo, Tianjin Anding Hospital, China *Correspondence: Wei Zheng, [email protected] This article was submitted to Adolescent and Young Adult Psychiatry, a section of the journal Frontiers in Psychiatry 08 2 2023 2023 14 111175430 11 2022 20 1 2023 Copyright (c) 2023 Zheng, Lan, Qin, Yang and Shi. 2023 Zheng, Lan, Qin, Yang and Shi This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Objective This systematic review of randomized controlled trials (RCTs) was conducted to explore the therapeutic effects and safety of active low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) versus sham LF-rTMS in children and adolescent patients with first-episode and drug-naive (FEDN) major depressive disorder (MDD). Methods A systematic literature search was performed, and data were extracted by two independent researchers. The coprimary outcomes were study-defined response and remission. Results A systematic search of the literature yielded 442 references, of which 3 RCTs (130 children and adolescents with FEDN MDD, 50.8% male, and mean age range from 14.5 to 17.5 years) met the inclusion criteria. Among the two RCTs (66.7%, 2/3) examining the effects of LF-rTMS on study-defined response and remission and cognitive function, active LF-rTMS was more efficacious than sham LF-rTMS in terms of study-defined response rate and cognitive function (all p < 0.05) but not regarding study-defined remission rate (all p > 0.05). No significant group differences were found with regard to adverse reactions. None of the included RCTs reported the dropout rate. Conclusion These findings preliminarily found that LF-rTMS could benefit children and adolescents with FEDN MDD in a relatively safe manner, although further studies are warranted. rTMS major depressive disorder first episode children adolescents National Natural Science Foundation of China 10.13039/501100001809 82101609 2019TS67 2019ZD06 Scientific Research Project of Guangzhou Bureau of Education202032762 Science and Technology Program Project of Guangzhou202102020658 Guangzhou Health Science and Technology Project20211A011045 Guangzhou Science and Technology Project of Traditional Chinese Medicine and integrated traditional Chinese and Western medicine20212A011018 China International Medical Exchange FoundationZ-2018-35-2002 Science and Technology Program Project of Guangzhou202102020658 Guangzhou Clinical Characteristic Technology ProjectGuangdong Hospital Association pmcIntroduction Major depressive disorder (MDD), as a leading cause of global disease burden (1), affects approximately 5-15% of children and adolescents (2). Children and adolescents with MDD are usually related to school dropout, pregnancy/parenthood, and unemployment (3). Furthermore, individuals suffering from MDD in childhood and adolescence have a relatively high risk for chronic recurrence, suicide, and long-term psychosocial impairment in adulthood (2, 4-6). Therefore, improvements in treating MDD among children and adolescents should positively affect public health. Initial treatment of children and adolescents with MDD may include a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioural therapy (CBT) (7). A Treatment for Adolescents with Depression Study (TADS) randomized controlled trial (RCT) found that CBT combined with fluoxetine provided a more favorable tradeoff between risk and benefit in adolescent patients with MDD than either treatment alone (7). However, up to 40% of adolescents suffering from MDD fail to respond to traditional treatment (8, 9). As a result, new and effective treatment approaches for MDD patients among children and adolescents are urgently needed. Repetitive transcranial magnetic stimulation (rTMS), as a noninvasive brain stimulation, is gaining attention in treating adults suffering from various conditions, including MDD and obsessive-compulsive disorder (OCD) (10-12). Repetitive transcranial magnetic stimulation uses a magnetic field to stimulate the cortex and depression-related areas with electrical currents and alter dysfunctional brain patterns (13, 14). Numerous RCTs have demonstrated the therapeutic effects of rTMS in adult patients with treatment-refractory depression (TRD) (15, 16). The utility of rTMS for adult patients with MDD and OCD who did not respond to medications has been approved by the US FDA (9, 17). Accumulating evidences found that rTMS also could accelerate the rapidity of the antidepressant response in adult patients suffering from first-episode MDD (18, 19). Case reports/series (20-22) and observational studies (23-28) reported that rTMS appeared to be suitable for children and adolescents diagnosed with MDD. However, the findings of RCTs (29-31) examining the therapeutic effects and safety of active low-frequency rTMS (LF-rTMS) versus sham LF-rTMS for children and adolescents with first-episode and drug-naive (FEDN) MDD have been inconsistent. Therefore, the primary aim in this systematic review of RCTs was to investigate the therapeutic effects and safety of active LF-rTMS versus sham LF-rTMS for children and adolescents with FEDN MDD. We hypothesized that active LF-rTMS would be more efficacious than sham LF-rTMS in ameliorating depressive symptoms in FEDN MDD patients among children and adolescents. Methods Search strategy and selection criteria To identify studies for inclusion in this systematic review, two researchers (ZJQ and XJL) independently searched Chinese Journal Net, WanFang databases, PsycINFO, Cochrane Library, PubMed, and EMBASE through November 4 2022. The search terms are listed in Appendix S1. Additionally, we manually searched reference lists of previous reviews (2, 9, 32) and the included RCTs (29-31) on active LF-rTMS versus sham LF-rTMS for children and adolescent patients with FEDN MDD. In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines (33), we included studies that fulfilled the following PICOS criteria. Participants: Children (6-11 years) (34) and adolescents (12-25 years) (35) with a diagnosis of first-episode MDD who did not receive any antidepressant treatment. In line with the methodology of a recent systematic review (35), adolescents were defined as those who are 12-25 years old rather than 13-18 years old. Intervention versus Comparison: active LF-rTMS versus sham LF-rTMS. Outcomes: The coprimary outcomes were study-defined response (i.e., at least 50% reduction in Hamilton Depression Rating Scale (HAMD) scores) and remission (i.e., at least 75% reduction in HAMD scores). Additional outcomes were cognitive function, dropout rate, and adverse events. Study: Only published RCTs on active LF-rTMS versus sham LF-rTMS for children and adolescents (6-25 years) with FEDN MDD were eligible for inclusion. Studies focusing on active LF-rTMS versus antidepressants (36) or high-frequency rTMS (HF-rTMS) combined with antidepressants versus antidepressant monotherapy (14) were excluded. Review articles and case reports/series were also excluded. Data extraction Two independent researchers (ZJQ and XJL) performed the data extraction from each included RCT, and any disagreements were resolved by joint discussion. We extracted data using a standardized form including author, year of publication, study design, rTMS protocol, and primary and secondary outcomes. Additional data were requested by contacting the original study author(s), if necessary. Study quality assessment The quality of the RCTs was independently assessed by the same two researchers (ZJQ and XJL) using the Jadad scale (37) and the Cochrane risk of bias (38). As reported previously (39), RCTs were considered "high quality" when the Jadad score was >=3. Results Study selection Our initial search of the above English and Chinese databases retrieved 442 references . Finally, 3 RCTs (29-31) conducted in China met the inclusion criteria of this systematic review. The screening process for the literature is presented in Figure 1. Figure 1 PRISMA flow diagram. Study characteristics The participant characteristics and LF-rTMS parameters of the three included RCTs (29-31) are summarized in Table 1. The studies (n = 130) were conducted between 2015 and 2019, comparing active LF-rTMS (n = 65) and sham LF-rTMS (n = 65) for children and adolescents with FEDN MDD. Their mean ages ranged from 14.5 to 17.5 years, and more than half (50.7%) of the children and adolescents with FEDN MDD were male. The LF-rTMS treatment duration varied from 10 days (2 RCTs (29, 30)) to 20 days (1 RCT (31)). The detailed LF-rTMS protocol of each included RCT is summarized in Table 1. Table 1 Participant characteristics and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) parameters of each study included in this systematic review. Study (country) Number of patientsa Participants: -Diagnosis -Diagnostic criteria -Setting -Illness duration (months) -Male (%) Mean age (years) (range) LF-rTMS treatment duration (days) Intervention versus control groups; number of patients (n) -Intensity (%MT) -Frequency (Hz) -Site -Number of trains per day -Train duration (s) -Intertrain duration (s) -Pulses per session -Number of sessions -Total pulses Jadad score (29) (China) 40 -FEDN MDD -DSM-IV -NR -1.1 -45 14.8 (12-18) 10 1. Active LF-rTMS; n = 20 2. Sham stimulation; n = 20 -70 -0.5 R-DLPFC -40 -10 -2 -200 -10 -2000 1 (31) (China) 60 -FEDN MDD -CCMD-3 -NR -NR -55 14.5 (10-16) 20 1. Active LF-rTMS; n = 30 2. Sham stimulation; n = 30 -100 -1 R-PFC -80 -10 -5 -800 -20 -16,000 1 (20) (China) 30 -FEDN MDD -DSM-IV -NR -6.3 -50 17.5 (15-21) 10 1. Active LF-rTMS; n = 15 2. Sham stimulation; n = 15 -80 -1 R-DLPFC -15 -40 -20 -600 -10 -6,000 2 a Overall number of participants. CCMD-3 = Chinese Classification and Diagnostic Criteria of Mental Disorders 3rd edition; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders 4th edition; FEDN = first-episode and drug-naive; MDD = major depressive disorder; MT = motor threshold; NR = not reported; R-DLPFC = right dorsolateral prefrontal cortex; R-PFC = right prefrontal cortex; LF-rTMS = low-frequency repetitive transcranial magnetic stimulation. Assessment of study quality As shown in Table 1, the Jadad score ranged from 1 (2 RCTs (29, 31)) to 2 (1 RCT (30)); thus, none of the included RCTs fulfilled the criteria of high quality. All RCTs were rated as low risk regarding attrition and reporting bias according to the Cochrane risk of bias . Figure 2 Cochrane risk of bias +: Low risk of bias, -: High risk of bias,?: Unclear risk of bias, nd: not determined. Study-defined response and remission Among the included three RCTs, one RCT (33.3%, 1/3) (29) did not report the rates of study-defined response and remission (Table 2) and found a significant superiority of active LF-rTMS over sham LF-rTMS in improving the depression subfactor scores of the Children's depression inventory (CDI; all p < 0.05). In Han et al.'s study (31), a significant superiority of active LF-rTMS over sham LF-rTMS was found for study-defined response (40.0 vs. 13.3%; p < 0.05) between active LF-rTMS and sham LF-rTMS but not for study-defined remission (13.3 vs. 3.3%; p > 0.05). Similarly, a significant superiority of active LF-rTMS over sham LF-rTMS was found for study-defined response (46.7 vs. 0%, p < 0.05) but not for study-defined remission (0 vs. 0%, p > 0.05) in Zhang et al.'s study (30). Table 2 Active versus sham LF-rTMS for adolescent patients with FEDN depression: study-defined response and remission. Study Treatment outcomes Defination Active LF-rTMS group Sham stimulation group Findings (29) (China) Study-defined response NR NR NR NA Study-defined remission NR NR NR NA (31) (China) Study-defined response Reduction from baseline of >= 50% in the HAMD total score 40.0% (12/30) 13.3% (4/30) P < 0.05 Study-defined remission Reduction from baseline of >= 75% in the HAMD total score 13.3% (4/30) 3.3% (1/30) P > 0.05 (30) (China) Study-defined response Reduction from baseline of >= 50% in the HAMD total score 46.7% (7/15) 0% (0/15) P < 0.05 Study-defined remission Reduction from baseline of >= 75% in the HAMD total score 0% (0/15) 0% (0/15) P > 0.05 FEDN = first-episode and drug-naive; HAMD = Hamilton depression rating scale; NR = not reported; LF-rTMS = low-frequency repetitive transcranial magnetic stimulation. Cognitive function Although 66.7% (2/3) of RCTs investigated the cognitive effects of active LF-rTMS versus sham LF-rTMS (Supplementary Table 1), their data measured by using different measures were not pooled. As shown in Supplementary Table 1, two RCTs consistently found that active LF-rTMS provided a significant improvement in cognitive function over sham LF-rTMS as measured by the Wisconsin Card Sorting Test (WCST) (31) and the cognitive subscale of HAMD (30), respectively. Dropout rate and adverse events As depicted in Supplementary Table 2, none of the included RCTs reported the dropout rate. Only one RCT (30) (33.3%, 1/3) reported adverse events, finding no significant difference regarding dizziness, nausea, or insomnia between the two groups (all p > 0.05; Supplementary Table 2). Discussion To the best of our knowledge, this article is the first systematic review of RCTs to investigate the effectiveness and safety of active LF-rTMS versus sham LF-rTMS for children and adolescents (6-25 years) with FEDN MDD. Only three RCTs (29-31) involving 130 subjects with FEDN MDD among children and adolescents were included in this systematic review. The major findings of this systematic review were as follows: (1) active LF-rTMS was more efficacious than sham LF-rTMS in terms of the study-defined response rate and the improvement of cognitive function; and (2) there is a strong indication that LF-rTMS was relatively safe and well tolerated in subjects with FEDN MDD among children and adolescents, although better quality studies are warranted. In this systematic review, LF-rTMS as a stand-alone treatment appears to be effective for children and adolescents with FEDN MDD, although long-term efficacy was not reported. A recent RCT (n = 103) examining the potential therapeutic role and safety of active LF-rTMS versus sham LF-rTMS for adolescents with TRD found that 41.7% responded, and 29.2% met the criteria of remission with active LF-rTMS (40). Numerous RCTs (14) and meta-analyses (2) found that rTMS as an adjunctive therapy is safe and effective in children and adolescents with MDD. Importantly, several recent studies found that LF-rTMS and antidepressants were equally efficacious in reducing depressive symptoms in children and adolescents with MDD (41). Taken together, these findings provide preliminary support for the utility of LF-rTMS in children and adolescents with MDD. For other noninvasive brain stimulations, such as transcranial direct current stimulation (tDCS) (42-44) and electroconvulsive therapy (45, 46), another objective is to monitor the cognitive effects of rTMS. Consistent with previous meta-analyses focusing on adult patients with MDD (47, 48), this systematic review also found that a therapeutic rTMS course for child and adolescent patients with FEDN MDD may produce modest cognitive enhancing effects. A possible explanation is that cognitive effects were secondary to mood improvement (47). However, the WCST and the HAMD measure used in the included two RCTs (30, 31) do not appear to be suitable for evaluating cognitive performance in MDD. The Assessment of Neuropsychological Status (RBANS) (49) or the MATRICS Consensus Cognitive Battery (MCCB) (50) should be recommended to assess cognitive performance in individuals experiencing MDD in clinical trials. Thus, the cognitive effects of active LF-rTMS compared to sham LF-rTMS should be further examined in FEDN MDD patients among children and adolescents. A recent RCT found that rTMS and tDCS (rTMS-tDCS) than single-tDCS produced greater improvement in neuropsychiatric symptoms (51). As a type of noninvasive cranial electrical stimulation, transcranial alternating current stimulation (tACS) can significantly improve depressive symptoms in adults with FEDN MDD (52). However, there have been no head-to-head studies that compared rTMS either with tACS or tDCS in child and adolescent patients with FEDN MDD. There are several limitations to this systematic review. First, data were not pooled due to the limited number of studies (3 RCTs) with the heterogeneity of significance between the studies. Second, the sample size (n = 130), ranging from 30 to 60, was relatively small. Third, the parameters of LF-rTMS used in the three included studies were varied. For example, the number of total pulses (Table 1) varied from 2,000 to 16,000, which may have resulted in different therapeutic effects and adverse effects. The optimal parameters of LF-rTMS as a stand-alone treatment for FEDN MDD patients among children and adolescents remain unclear. Interestingly, a recent RCT found a significant superiority of Stanford neuromodulation therapy (SNT), a neuroscience-informed accelerated intermittent theta-burst stimulation protocol (90,000 total pulses), in improving depressive symptoms in adults with TRD when compared to sham stimulation (53). Thus, the efficacy and the safety of SNT for patients with MDD among children and adolescents should be examined. Fourth, all 3 RCTs (29-31) included in this study were conducted in China and involved only Chinese children and adolescents. Thus, the findings of the present study could not be generalizable to children and adolescents in other countries. Finally, this systematic review has not been registered. Conclusion These findings preliminarily found that LF-rTMS could benefit children and adolescents with FEDN MDD in a relatively safe manner, although further studies are warranted. Data availability statement The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author. Author contributions X-JL and Z-JQ selected studies and extracted the data. WZ reviewed all the data and helped mediate disagreements, wrote the first draft. All authors contributed to the article and approved the submitted version. Funding This study was funded by National Natural Science Foundation of China (82101609), Scientific Research Project of Guangzhou Bureau of Education (202032762), Science and Technology Program Project of Guangzhou (202102020658), Guangzhou Health Science and Technology Project (20211A011045), Guangzhou Science and Technology Project of Traditional Chinese Medicine and integrated traditional Chinese and Western medicine (20212A011018), China International Medical Exchange Foundation (Z-2018-35-2002), Guangzhou Clinical Characteristic Technology Project (2019TS67), Science and Technology Program Project of Guangzhou (202102020658) and Guangdong Hospital Association (2019ZD06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary material for this article can be found online at: Click here for additional data file. References 1. Smith K . Mental health: a world of depression. Nature. (2014) 515 :180-1. doi: 10.1038/515180a, PMID: 25391942 2. Qiu H Liang K Lu L Gao Y Li H Hu X . 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PMC10000295 | Front Psychol Front Psychol Front. Psychol. Frontiers in Psychology 1664-1078 Frontiers Media S.A. 10.3389/fpsyg.2022.1027108 Psychology Original Research Avoidant authority: The effect of organizational power on decision-making in high-uncertainty situations Shortland Neil D. 1 * McCusker Maureen E. 2 Alison Laurence 3 Blacksmith Nikki 4 Crayne Matthew P. 5 Thompson Lisa 1 Gonzales Joseph 6 McGarry Presley 1 Stevens Catherine 1 1School of Criminology and Justice Studies, University of Massachusetts Lowell, Lowell, MA, United States 2Institutional Research and Decision Support, Virginia Commonwealth University, Richmond, VA, United States 3Institute for Risk and Uncertainty, University of Liverpool, Liverpool, United Kingdom 4School of Business, University at Albany, Albany, NY, United States 5Department of Management, American University, Washington, DC, United States 6Department of Psychology, University of Massachusetts Lowell, Lowell, MA, United States Edited by: Kittisak Jermsittiparsert, University of City Island, Cyprus Reviewed by: Narentheren Kaliappen, Universiti Utara Malaysia, Malaysia; Kathanyoo Kaewhanam, Kalasin University, Thailand; Phimlikid Kaewhanam, Kalasin University, Thailand; Arthit Thongin, Sukhothai Thammathirat Open University, Thailand *Correspondence: Neil D. Shortland, [email protected] This article was submitted to Organizational Psychology, a section of the journal Frontiers in Psychology 24 2 2023 2022 13 102710824 8 2022 25 11 2022 Copyright (c) 2023 Shortland, McCusker, Alison, Blacksmith, Crayne, Thompson, Gonzales, McGarry and Stevens. 2023 Shortland, McCusker, Alison, Blacksmith, Crayne, Thompson, Gonzales, McGarry and Stevens This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Individuals in positions of power are often required to make high-stakes decisions. The approach-inhibition theory of social power holds that elevated power activates approach-related tendencies, leading to decisiveness and action orientation. However, naturalistic decision-making research has often reported that increased power often has the opposite effect and causes more avoidant decision-making. To investigate the potential activation of avoidance-related tendencies in response to elevated power, this study employed an immersive scenario-based battery of least-worst decisions (the Least-Worst Uncertain Choice Inventory for Emergency Responses; LUCIFER) with members of the United States Armed Forces. In line with previous naturalistic decision-making research on the effect of power, this research found that in conditions of higher power, individuals found decisions more difficult and were more likely to make an avoidant choice. Furthermore, this effect was more pronounced in domain-specific decisions for which the individual had experience. These findings expand our understanding of when, and in what contexts, power leads to approach vs. avoidant tendencies, as well as demonstrate the benefits of bridging methodological divides that exist between "in the lab" and "in the field" when studying high-uncertainty decision-making. least-worst decision social power redundant deliberation organizational culture approach/avoid Army Research Institute for the Behavioral and Social Sciences 10.13039/100009919 W911NF-17-0209 This study was funded by the Army Research Institute (award W911NF-17-02-0109). pmcIntroduction In the face of multiple, unappealing options, individuals often must commit to courses of action that are less than ideal (Alison et al., 2013). Such decisions can manifest in a range of situations and across a range of organizational levels (Klein, 1993), and include deciding how, if, and when to lockdown a country in response to a global pandemic, or to how to deal with a potentially hostile civilian in a police or military encounter. These decisions all involve multiple potentially negative courses of action, and often have significant, long-lasting implications for the decision-maker, those involved, and society at large (Shortland et al., 2019). Theories of decision-making often center on the assumption that the decision-maker chooses the course of action by identifying the "best" or the choice with the highest "expected value" (Simon, 1955, 1978; Tversky and Kahneman, 1974; Kahneman and Tversky, 1979; Hastie and Dawes, 2009). Yet in many cases, decision makers are presented with courses of action that have uncertain outcomes and in which each potential outcome could have negative implications (Klein, 1993; Cannon-Bowers and Salas, 1998). Such decisions violate traditional theories of decision-making because a "best" course of action cannot be identified (Shortland et al., 2018). Psychologists who study high-uncertainty decision-making in the field refer to these kinds of decisions as "least-worst" in that the decision-maker must calculate and choose the option that causes the least harm from a series of harmful options (Power and Alison, 2017). Least-worst decisions require the decision-maker to take decisive action and overcome fear, doubt, and uncertainty to commit to a least-worst choice (Alison et al., 2018; Shortland et al., 2019). However, research has indicated that the process of least-worst decision-making can often become derailed, resulting in decision inertia. There are several manifestations of decision inertia, all of which involve the failure to make a necessary decision in time, or the failure to make any decision at all (van den Heuvel et al., 2012). Decision-makers can avoid the choice (decision avoidance; Anderson, 2003), cognitively ruminate over the options for no overall gain (redundant deliberation; Shortland and Alison, 2020), or fail to implement a chosen course of action (implementation failure; van den Heuvel et al., 2012). Decision inertia often stems from decision-makers becoming trapped between an approach-based choice that maximizes progress toward task accomplishment and an avoidance-based choice that minimizes any possible or further harm (Power and Alison, 2017; Power, 2018). Research has begun to explore the environmental antecedents of decision inertia (van den Heuvel et al., 2012; Power and Alison, 2017) as well as individual differences in susceptibility to decision inertia (Shortland et al., 2019, 2020a,2020b; Shortland and Alison, 2020). One consistent finding in the field is that individuals in positions of power are at a greater risk of redundant deliberation (Alison et al., 2015a,b; Power and Alison, 2017; Shortland et al., 2019). Naturalistic decision-making research has found that, when operating within organizational settings, individuals who hold positions of power avoid committing to a course of action when they anticipate negative consequences because of fears of accountability (Waring et al., 2013) and negative feedback (Eyre et al., 2008), especially when the individual cannot fully justify their choice (Brooks, 2011). From a theoretical standpoint, however, such findings are especially interesting because they run contrary to the body of research that shows that positions of power improve decision-making by removing inhibitions and encouraging action (e.g., Maner et al., 2007, 2010; Smith and Bargh, 2008). In organizational settings, power is defined as the ability to control resources, one's own and others,' without social interference (Galinsky et al., 2003). Power is also defined as the ability to influence another person to do something they would not do without the presence of such power (Hashemian et al., 2019). Accordingly, individuals who hold higher status (rank) in an organization are guaranteed power due to legitimacy (French and Raven, 1959; Boksem et al., 2012), especially in high-stakes situations, because of the control of others, resources, and fewer social barriers to action. It is argued that having power allows the individual to operate with more free will (i.e., less inhibition; Weber, 1914). Power increases approach motivations and assists in the process of goal setting and action prioritization (Cho and Keltner, 2020) by allowing the decision-maker to focus on the task (or goal) at hand (Smith and Bargh, 2008; DeWall et al., 2011). Guinote (2007) found that those with higher power were faster decision-makers and faster to initiate goal pursuit. Cho and Keltner (2020) also found that those with power make faster decisions and act more promptly. Powerful individuals also engage in less deliberate decision-making processes (Fiske and Depret, 1996) and have less foresight (consideration of "what happens if"; Guinote and Kim, 2020). Power works throughout the entire motivational process, from increasing goal setting, to early action, through to completion of the task (Guinote, 2007). Power is also especially beneficial under pressure with high stakes (Kang et al., 2015). Pike and Galinsky (2020) surmised that power releases the psychological brakes on action by (1) making failure seem less probable and feel less painful (2) decreasing the "downsides" of action, (3) shrouding the feelings and thoughts of others, (4) diminishing the perceived social costs of action, and (5) increasing greater goal focus by limiting goal-inhibiting distractions and focusing the mind on action. From a theoretical standpoint, power causes activation of the behavioral activation system (BAS; Keltner et al., 2003; Cho and Keltner, 2020). The BAS is the main driving force of approach behavior within Gray's (1987) Reinforcement Sensitivity Theory (RST). Within the RST framework, stimuli perceived as positive activate the Behavioral Activation System (BAS) and approach behaviors toward target goals, while stimuli perceived as negative activate the Fight, Flight, Freeze System (FFFS), motivating the individual to avoid potential threats. The Behavioral Inhibition System (BIS) coordinates the response by attempting to resolve conflicting inputs when a stimulus activates both BAS and FFFS (McNaughton and Gray, 2000). RST provides a model of how animals, including humans, respond to motivationally significant (i.e., "reinforcing") stimuli, and how this motivation is mediated by the neuropsychological activity (Corr and Cooper, 2016). Power is often linked to BAS activation because research has found that power increases a generalized approach orientation (Keltner et al., 2003; Cho and Keltner, 2020), optimism and confidence (Fast et al., 2012); and power increases disinhibited behavior (Gonzaga et al., 2008). Furthermore, Krupic and Corr (2017) posit that BAS processes are associated with a "fast lifestyle," typified by bold, aggressive, and impulsive behavior (Wolf et al., 2007). This has led to the approach-inhibition theory of power, in which "elevated power (which relates to increased rewards and freedom) activates approach-related tendencies, whereas reduced power (which relates to increased threat, punishment, and social constraint) activates inhibition-related tendencies" (Cho and Keltner, 2020, p. 196). Contrary to the approach-inhibition theory of power, the naturalistic decision-making research outlined above implies that in high-uncertainty, blame-centric environments power increases avoidance. As such, rather than BAS activation, power increases FFFS activation, leading to FFFS activation, or become stuck deciding between approach and avoidant courses of action (a failure of BIS to reconcile concurrent FFFS and BAS activation). FFFS/BIS activation is associated with risk-assessment and can be an adaptive process of caution and weighing up all the possibilities (Perkins and Corr, 2006). However, FFFS/BIS activation can also decrease performance by increasing doubt, indecision, worry, and engagement of time-wasting "displacement activities" (Corr et al., 2016), and therefore decision inertia (Alison et al., 2013). FFFS/BIS activation is driven by fear and anxiety and is viable to propose that the dissociation of findings between laboratory-based research and naturalistic decision-making research is likely driven by the lack of context and accountability in laboratory research paradigms. While laboratory studies often rely on minor tasks with little to no accountability or consequence, naturalistic decision-making research observes high-uncertainty decisions in contexts in which the outcomes of a decision could be grave and the individual is accountable for their actions (Alison et al., 2013; Waring et al., 2013). Such situations are far more likely to evoke FFFS/BIS-associated feelings of fear, anxiety, and self-evaluation (McNaughton and Corr, 2004; Corr et al., 2016). What this means, therefore, is that while the approach-inhibition theory of power may be appropriate in low-stakes environments, it may not apply to those contexts in which power is associated with blame and accountability. Instead, in such contexts there is significant warrant to propose that power can cause FFFS/BIS activation and concurrent tendencies to either (1) engage in avoidant behavior and/or (2) become inert and trapped between approach/avoid motivations. Research questions This study is interested in the degree to which being put in a position of power causes tendencies to take approach-orientated actions. To test this research question, the present study conducts a controlled experimental test of power and decision-making using an ecologically valid inventory of high-uncertainty least-worst decisions with a sample of senior decision-makers. Specifically, we hypothesize that: H1: High power is positively related to the speed it takes to make a least-worst decision. H2: High power is positively related to perceived difficulty of making a least-worst decision. H3: High power is negatively related to the tendency to make approach-orientated least-worst decisions. Materials and methods Participants A total sample of 234 United States (U.S.) Army soldiers, including both officers and enlisted, across a range of ranks completed this study (77.78% male, age: M = 31.81 years, SD = 5.99; 61.54% had been previous deployed to war overseas) from a total of three U.S. Army bases across the nation. Recruitment for this study was completed in support of a wider study on individual differences in decision-making conducted in support of the Foundational Science Research Unit (FSRU) U.S. Army Research Institute (ARI). Data were collected using Qualtrics (Provo, UT) software installed on individual iPad tablets provided to the individual soldiers. Two members of the research team administered the assessments to the soldiers, ensuring adequate distance among the soldiers for privacy in completing the assessments. The entire assessment took approximately 45 min to complete. Procedure Decision-making scenarios (least-worst uncertain choice inventory for emergency responses) Participants completed the Least-worst Uncertain Choice Inventory for Emergency Responses (LUCIFER; see Shortland et al., 2020a,b). LUCIFER adopts a two-alternative forced choice (2AFC) approach in which the participant faces a range of least-worst scenarios. Each LUCIFER scenario was developed from critical decision method (CDM) interviews with active service members of armed forces, emergency service responders, and members of the police force to ensure validity (Shortland et al., 2019; Shortland and Alison, 2020). The version of LUCIFER used in this study consisted of eight scenarios (16 total decisions). Each 2AFC choice in LUCIFER represents one approach-oriented decision (i.e., an action that makes a positive impact on the goal progress) and one avoidant-oriented decision (i.e., not taking any action that could result in harming others). After each scenario, participants were asked about their reactions to the decision-making process including perceived difficulty and perceived power. The LUCIFER study flow is presented in Figure 1. Following completion of the eight decision scenarios, participants were asked to complete a decision-making style scale. FIGURE 1 Study flow with sample rank manipulation. Power manipulation There exist multiple forms of social hierarchy in the U.S. Army, both formal and informal. However, for the purposes of this study, we refer to the social power by a soldier's formal rank given that Army soldiers' power increases with their rank. Thus, in the present study, power was manipulated by adjusting the rank of the decision-maker for each scenario. Specifically, participants were informed that they were operating (and thus making decisions) as if they were a higher rank ("Battalion Commander") or a lower rank ("Company Commander"). Participants were informed of their rank prior to listening to the first audio clip. Following the scenario, the participant was asked to indicate how much power they perceived themselves to have in the decision scenario. Rank manipulations have previously been used to examine the effect of power (Gobel et al., 2018). Participants' own actual rank was measured and controlled for. Measures Within-participant time to decision Participant time to decision scores were mean-centered. For within-participant time to decision, scores of zero indicate the average time to decision of a participant across all sessions, negative scores indicate time to decision scores below the participant's average time to decision score, and positive scores indicate time to decision scores above the participant's average time to decision score. Within-participant power A participant's subjective perception of their power was assessed using a single item scale that asked the degree to which they felt they had power in the given scenario (0 = no power, 100 = high power). Scores were mean-centered so as to reduce the chances of multicollinearity (Aiken et al., 1991). This within-participant score represents changes in power, within a participant, across scenarios. Within-participant confidence Power increases self-confidence (Brinol et al., 2007; Fast et al., 2012) and previous research with the LUCIFER tool has shown that confidence is correlated with decision-making speed, difficulty and approach/avoidant tendencies (Shortland et al., 2020a,b). As such, participant confidence scores were measured and controlled for using a mean-centered within-participant confidence score. Confidence in their decision was self-reported on a scale of 0 (no confidence) to 100 (total confidence) at the end of each scenario. Control variables Based on findings from previous research with LUCIFER (Shortland et al., 2020a,b), we controlled for expertise and avoidant decision-making. Avoidant decision-making styles are associated with general avoidant decision-making (Dewberry et al., 2013); in this study we measured and controlled for trait-level tendencies to make avoidance choices using the general decision-making style avoidant subscale (DMS Avoid, Scott and Bruce, 1995). Naturalistic decision-making research places immense importance on the role of expertise in decision-making (Klein, 1998). As such, this research involved an expertise manipulation in which participants made decisions in scenarios, which were military situations (domain-specific) or non-military ones (domain-general). Analytic approach A multilevel structural equation model was used to examine the nested data structure. All data analyses were conducted in R version 3.6.1 (R Core Team, 2019) using the lme4 multilevel modeling package (Bates et al., 2020). Identification of data nesting structure In accordance with previous social science research that uses structural equation modeling (SEM) frameworks to evaluate complex hypotheses with nested data, we evaluated absolute model fit to identify the ideal nesting structure for hypothesis testing (Sterba et al., 2014). This was conducted by comparing a series of intercept only models for each outcome; multilevel logistic regression for approach/avoidant decisions, and multilevel modeling for both decision time and difficulty. Both of the single nesting structure models were compared against the model with both nesting structures using a likelihood ratio test (Snijders and Bosker, 1999; Raudenbush and Bryk, 2002; Gelman and Hill, 2007) to determine the optimal nesting structure for each outcome. Nesting of avoid/approach decisions in both soldier-participants and scenarios resulted in a significant improvement of fit when compared to nesting only in soldier-participants [Dkh2(1) = 466.71, p < 0.01], but not when compared to nesting only in scenarios [Dkh2(1) = 0.02, p = 0.88]. These findings indicate that there was not significant variability in this outcome attributable to between-participant variability (i.e., no within-person nesting), but there was between scenarios (see Table 1). Due to this, subsequent analyses of avoid/approach decisions only utilized a within-scenario nesting structure. Nesting of time to decision scores in both soldier-participants and scenarios resulted in a significant improvement of fit when compared to nesting only in soldier-participants [Dkh2(1) = 145.8, p < 0.01] and nesting only in scenarios [Dkh2(1) = 221.77, p < 0.01], indicating that significant variability in this outcome is attributable to both between-participant and between-session variability (see Table 1). Due to this, subsequent analyses of time to decision utilized both a within-participant and within-scenario nesting structure. Nesting of self-rated decision difficulty scores in both soldier-participants and scenarios resulted in a significant improvement of fit when compared to nesting only in soldier-participants [Dkh2(1) = 112.63, p < 0.01] and nesting only in scenarios [Dkh2(1) = 607.90, p < 0.01], indicating that significant variability in this outcome is attributable to both between-participant and between-session variability (see Table 1). Due to this, subsequent analyses of decision difficulty utilized both a within-participant and within-scenario nesting structure. TABLE 1 Participant-soldier, and scenario nesting models. Model Outcome Nesting variable(s) ICC P Avoid/approach Participant-soldier 0% S Avoid/approach Scenario 15.90% PS Avoid/approach Participant-soldier 0.40% Scenario 15.90% P Time to decision Participant-soldier 11.90% S Time to decision Scenario 4.50% PS Time to decision Participant-soldier 12.10% Scenario 4.50% P Decision difficulty Participant-soldier 23.30% S Decision difficulty Scenario 3.10% PS Decision difficulty Participant-soldier 23.40% Scenario 3.10% Identification of optimum predictive model Results showed that the baseline model (Model B) of avoid/approach decisions fit the data significantly worse [Dkh2(6) = 89.54, p < 0.01] than the model including interactions with scenario type (Model M), but did not differ significantly [Dkh2(6) = 6.62, p = 0.36] from the model including interactions with the rank manipulation (Model R). Thus, Model M was identified as the optimum model for avoid/approach decisions (see Table 2). Similarly, the baseline model (Model B) of time to decision fit the data significantly worse [Dkh2(6) = 73.36, p < 0.01] than the model including interactions with scenario type (Model M), but did not differ significantly [Dkh2(6) = 5.82, p = 0.44] from the model including interactions with the rank manipulation (Model R). Thus, Model M was identified as the optimum model for time to decision (see Table 3). TABLE 2 Predictive model for approach/avoid decisions. Predictor Estimate Standard error p-value Odds ratio Intercept 0.74 0.5 0.14 2.10 Rank 0.12 0.12 0.34 1.13 Military -1.11 0.64 0.08 0.33 Phase -0.64 0.12 <0.01 0.53 Confidence -0.01 0.01 0.17 0.99 Power -0.01 0.004 0.17 0.99 DMS avoid -0.02 0.02 0.19 0.98 Time decision -0.08 0.01 <0.01 0.93 Military: Rank -0.07 0.15 0.65 0.93 Military: Phase 1.04 0.15 <0.01 2.83 Military: Confidence 0.01 0.006 0.03 1.01 Military: Power 0.01 0.005 <0.01 1.01 military: DMS avoid 0.01 0.02 0.78 1.01 Military: Time decision 0.08 0.02 <0.01 1.08 TABLE 3 Predictive model for decision-making time. Predictor Estimate Standard error p-value Intercept 5.87 1.09 <0.01 Rank 0.18 0.31 0.56 Military -1.96 1.26 0.15 Phase -1.00 0.30 <0.01 Confidence -0.07 0.01 <0.01 Power -0.02 0.01 0.15 DMS avoid 0.06 0.05 0.30 Avoid (vs. approach) -2.08 0.34 <0.01 Military: Rank -0.15 0.40 0.71 Military: Phase 2.55 0.38 <0.01 Military: confidence 0.004 0.02 0.81 Military: power 0.003 0.01 0.79 Military: DMS avoid -0.06 0.05 0.20 Military: avoid (vs. approach) 2.25 0.42 <0.01 However, the baseline model (Model B) of decision difficulty fit the data significantly worse than both the model including interactions with scenario type [Model M; Dkh2(6) = 14.50, p = 0.02] and the model including interactions with rank manipulation [Model R; Dkh2(6) = 20.69, p < 0.01]. Subsequent comparisons found that Model R did not significantly differ from the model including both scenario type and rank manipulation interactions [Model RM; Dkh2(5) = 7.70, p = 0.17], but that Model M did significantly differ from Model RM with respect to model fit [Dkh2(5) = 13.89, p = 0.02]. Thus, Model R was identified as the optimum model for decision difficulty (see Table 4). TABLE 4 Predictive model for decision difficulty. Predictor Estimate Standard error p-value Intercept 14.15 0.92 <0.01 Rank 1.31 0.66 0.05 Military 1.11 0.67 0.14 Confidence -0.09 0.01 <0.01 Power -0.02 0.01 <0.01 DMS avoid 0.1 0.07 0.13 Avoid (vs. approach) -0.03 0.27 0.90 Time decision 0.09 0.02 <0.01 Rank: military -0.57 0.41 0.16 Rank: confidence 0.02 0.01 0.12 Rank: power 0.03 0.01 <0.01 Rank: DMS avoid -0.1 0.05 <0.01 Rank: avoid (vs. approach) -0.11 0.38 0.78 Rank: time decisions -0.03 0.03 0.40 Results Descriptive statistics and correlations are presented in Tables 5, 6. TABLE 5 Descriptive statistics for total sample. Variable Mean St. deviation Scenario level variables (N = 3,728) Decision time (DT) 6.10 6.83 Decision difficulty (DD) 15.87 6.65 Confidence 82.58 19.64 Power 78.57 22.82 Individual level variables (N = 234) Avoid/Approach score 7.53 1.88 Age 31.81 5.99 DMS avoid 10.69 3.82 N % Gender (Ref = female) Male (Yes = 1) 122 52.14 Scenario level variables (N = 8) Military scenarios 5 TABLE 6 Correlations between input variables. Variable 1 2 3 4 5 6 7 8 9 1. Decision time - 2. Decision difficulty 0.130*** - 3. Confidence -0.161*** -0.261*** - 4. Power -0.067*** -0.133*** 0.475*** - 5. Avoid/approach score 0.005 0.001 0.029 0.011 - 6. Age 0.078*** 0.045** 0.097*** 0.043** 0.016 - 7. DMS avoid score 0.003 0.027 -0.114*** -0.028 -0.034* -0.026 - 8. Gender 0.010 -0.087*** 0.220*** 0.148*** 0.008 0.182*** -0.026 - 9. Military scenario 0.009 0.093*** -0.124*** -0.078*** -0.123*** 0.000 0.000 0.000 - *p < 0.05; **p < 0.01; ***p < 0.001. Power manipulation check In seven of the eight scenarios, rank manipulation led to increased perceived power. A between group ANOVA was used to assess the effect of rank manipulation on perceived power. In four of the eight scenarios, participants who were assigned the higher rank reported significantly higher levels of perceived power (see Table 7). As such, the power manipulation was effective in that as participant rank increased, the subjective perceptions of the subject's own power also increased. TABLE 7 Group differences for in perceived power by rank manipulation. Scenario type Rank A (lower) Rank B (higher) Mean difference (p-value) Scenario 1 (na = 108) (nb = 126) Military (domain-specific) 76.48 (23.56) 80.35 (20.84) 3.87 (p = 0.188) Scenario 2 (na = 109) (nb = 125) Military (domain-specific) 65.14 (27.62) 73.62 (25.26) 8.48 (p = 0.016)* Scenario 3 (na = 115) (nb = 119) Non-military (domain-general) 76.17 (24.00) 82.87 (18.41) 6.70 (p = 0.018)* Scenario 4 (na = 126) (nb = 108) Non-military (domain-general) 79.13 (21.38) 85.48 (18.55) 6.35 (p = 0.016)* Scenario 5 (na = 115) (nb = 119) Military (domain-specific) 76.20 (23.89) 82.58 (20.17) 6.38 (p = 0.027)* Scenario 6 (na = 115) (nb = 119) Military (domain-specific) 79.60 (20.41) 78.39 (23.83) 1.21 (p = 0.676) Scenario 7 (na = 132) (nb = 102) Non-military (domain-general) 80.33 (25.29) 80.72 (22.67) 0.39 (p = 0.903) Scenario 8 (na = 119) (nb = 115) Military (domain-specific) 78.24 (22.09) 78.77 (21.11) 0.53 (p = 0.849) *p < 0.05; **p < 0.01; ***p < 0.001. Decision-making speed We hypothesized that greater subjective perception of power will be positively related to the speed it takes to commit to a course of action when making a least-worst decision. The identified model indicated there were two significant interactions between scenario type (military vs. non-military) and other predictors. Avoid (vs. approach) decisions interacted with scenario type (B = 2.25, SE = 0.42, p < 0.01), such that in non-military scenarios making an avoid decision was associated with faster decision time (B = -2.08, SE = 0.34, p < 0.01), whereas in military scenarios decision time did not differ significantly as a function of the decision type (avoid vs. approach; B = 0.18, SE = 0.26, p = 0.48). In addition to these interaction effects, a main effect of within-subject confidence was found, whereby greater perceived within-subject confidence predicted faster decision time (B = -0.07, SE = 0.01, p < 0.01) across all decisions. Based on these results we find support for hypothesis 1. Decision difficulty We hypothesized that greater perceived power will be positively related to the perceived difficulty of making a least-worst decision. The identified model indicated there were two significant interactions between the rank manipulation and other predictors. Specifically, rank manipulation had a significant interaction with within-participant power (B = 0.03, SE = 0.01, p = 0.03) participants were assigned a lower rank, their ratings of decision difficult increased when they perceived higher power (B = -0.02, SE = 0.01, p < 0.01) but this relationship did not hold when they were in assigned higher ranking scenarios (B = 0.01, SE = 0.01, p = 0.53). Additionally, there was an interaction between the rank manipulation and participants' DMS Avoid scale scores (B = -0.10, SE = 0.38, p = 0.04), suggesting that the relationship between DMS Avoid scale scores and decision difficulty differ significantly as a function of the rank manipulation. However, DMS Avoid scale scores were not significantly related to decision difficulty scores for either the lower rank (B = 0.10, SE = 0.07, p = 0.13) or upper rank scenarios (B = -0.01, SE = 0.01, p = 0.94). In addition to these interaction effects, we found several main effects. Specifically, time to decision was found to positively predict decision difficulty (B = 0.09, SE = 0.02, p < 0.01), while within-subject confidence was found to negatively predict decision difficulty (B = -0.09, SE = 0.01, p < 0.01). Finally, our results showed a main effect of rank manipulation such that soldier-participants reported greater perceived difficulty when in assigned a higher rank (vs. a lower rank; B = 1.31, SE = 0.66, p = 0.048). These findings provide support for hypothesis 2. Avoid/approach decision choice We hypothesized that increased perception of power will be negatively related to the tendency to make approach-orientated decisions when making a least-worst decision. The identified model indicated there were several significant interactions between scenario type (military vs. non-military) and predictors. Scenario phase (scenario decision 2 vs. decision 1) had a significant interaction with scenario type (B = 1.04, SE = 0.15, p < 0.01, OR = 1.01) such that in non-military scenarios participants were less likely to make an avoid decision during the second scenario prompt than the first (B = -0.64, SE = 0.12, p < 0.01, OR = 0.53), but in military scenarios participants were more likely to make an avoid decision during the second scenario prompt than the first (B = 0.40, SE = 0.09, p < 0.01, OR = 1.50). Within-participant power also had a significant interaction with scenario type (B = 0.01, SE = 0.005, p < 0.01, OR = 1.01) such that in non-military scenarios there was no effect of within-participant power (B = -0.006, SE = 0.004, p = 0.17, OR = 0.99), but that in military scenarios greater perceived within-participant power predicted increased likelihood of making an avoidant decision (B = 0.007, SE = 0.003, p < 0.01, OR = 1.01). Similarly, within-participant time to decision had a significant interaction with scenario type (B = 0.08, SE = 0.02, p < 0.01, OR = 1.08), such that in non-military scenarios when participants took longer to make a decision they were significantly less likely to make an avoidant decision (B = -0.08, SE = 0.01, p < 0.01, OR = 0.92), but there was no significant relation between time to make a decision and likelihood of making an avoidant (vs. approach) decision for military scenarios (B = 0.004, SE = 0.008, p = 0.65, OR = 1.00). While a significant interaction between within-participant confidence and scenario type (B = 0.01, SE = 0.006, p = 0.03, OR = 1.01) was identified, there were no significant effects of within-participant confidence as a predictor of the likelihood of making an avoid (vs. approach) decision in either non-military (B = -0.007, SE = 0.005, p = 0.17, OR = 0.99) or military scenarios (B = 0.006, SE = 0.003, p = 0.07, OR = 1.01). These findings provide support for hypothesis 3. Discussion Understanding the relationship between power and decision-making tendencies is critically important given that those in positions of power often face high stakes decisions that involve juggling approach/avoidance courses of action between the lesser of two evil outcomes. The approach-inhibition theory of social power holds that elevated power activates approach-related tendencies, leading to decisiveness and action orientation. However, naturalistic decision-making research has often reported that increased power often has the opposite effect and causes more avoidant decision-making. Thus, while the approach-inhibition theory posits a single, linear relationship between power and BAS activation, real-world evidence seems to imply that, in some conditions, power can lead to tendencies to avoid (and thus BIS activation). Accordingly, this study sought to explore the effect of social power on least-worst decision-making. In line with our hypotheses, and the wider naturalistic decision-making findings, this research found that increases in perceived power were associated with avoidant choices and increased difficulty. To the author's knowledge, this is the first experimental study to show that the theory of approach-inhibition may be missing the potential relationship between power and avoidance. This theoretical extension of the current linear conceptualization of power and BAS is critically important given the need to fully understand how the environment may impact on decision-maker in high-uncertainty situations. While the domain of laboratory-based research on decision-making has widely supported the assertion that power drives action (Guinote, 2007; Pike and Galinsky, 2020), findings from naturalistic decision-making research perhaps explains why this is not always the case. In a simulated study of counter-terrorism police decision-making, the presence of accountability (often associated with those in power; Rus et al., 2012) caused people to shift from approach goals (save lives) to an avoidant goal (save self and own career; van den Heuvel et al., 2014). In fact, the study of organizational accountability has often found that accountability affects the choices that an individual makes and their ability to commit to a decision (van den Heuvel et al., 2012; Shortland et al., 2019). Accordingly, police officers' performance decreased when they felt accountable for their actions (Waring et al., 2013). This was suggested to stem from an increase in cognitive load due to additional concerns associated with being accountable. Accountability can also increase risk aversion, encouraging decisions that protect oneself and the consequences of one's actions, rather than a commitment to decisions that are the best action for the major incident (Alison et al., 2015a). This in turn can create redundant deliberation by competing with the desire to make a positive impact on the situation (Power and Alison, 2017). Such views of accountability would explain why increased perceived power was associated with tendencies to make avoidant choices. This view of accountability and rank may also explain the finding that higher rank led to lower perceived power in that higher ranks were viewed as being more constrained and associated with higher levels of accountability, and thus, contra-logically, individuals felt less powerful. The finding that participants did not show a marked improvement in approach tendencies, speed, or difficulty, when facing domain-specific decisions potentially stems from the notion that least-worst decisions, by nature, violate many of the contemporary models of expert decision-making. Principal features of expert decision-making are improved mental models and an increased ability to pattern-match (Allard et al., 1980). Least-worst decisions are often associated with "no analogies," and thus, individuals have no previous mental models that can be readily applied to the situations. Those who recall least-worst decisions often emphasize that they were "new" or "novel" (Shortland et al., 2019, 2020a; Shortland and Alison, 2020). This perhaps explains why, overall, domain expertise had little effect on decision-making. That said, participants were faster to make avoidant choices in situations for which they had no expertise. One view of this is that, in those situations in which participants had domain-expertise, they were better able to process the context of the decisions, and indeed the future outcomes or a choice ("what will happen if"). This may have led to a slowing of the decision-making process because while participants were equally avoidant in both types of scenario, their increased understanding of the context of a military scenario (that they have domain expertise in) added additional workload. Beyond supporting the elsewhere observed effect of power on avoidance, these findings raise questions about how we think about decision-making. For example, while naturalistic research has often focused on the processes that underpin decision-making, the role of motivation processes in decision-making is less often integrated. This study questions the degree to which the avoidance and approach tendencies identified elsewhere (Power and Alison, 2017), can be conceptualized in the approach and avoidance tendencies highlighted in Gray's (1987) RST. In this case, we can think of processes such as decision inertia as a manifestation of BIS processing, which has interesting implications for identifying the neurological, and state and trait personality factors that may play a role in the emergence of this behavior. Limitations More open research methodologies (such as LUCIFER) allow for the identification of the wider exogenous and endogenous pressures (e.g., accountability, trust and role confusion) that would, arguably, not manifest in more "closed" decision-making tasks (termed "immersive simulated learning environments"; see Alison et al., 2013). With that said, in this study, it is viable that the engagement and immersion of the participant increased the role of unmeasured variables to the interpretation. For example, while the context of leadership could have increased subjective perceptions of accountability, it is also possible that the audio immersion activated the BIS or fight, flight, freeze system (BIS/FFFS; McNaughton, 2004). While we do not advocate the use of research methodologies with lower fidelity, increasing the fidelity of the methodology (a strength of LUCIFER) does increase the potential extraneous variables that may have unintended, and unforeseen influences on behavior. As such, we encourage future research to measure wider organizational and ecological variables, such as a culture of accountability, that may play an important role in decision-making. Conclusion and future directions We increasingly ask for more accountability in those with power (e.g., police, military, and world leaders; Rossler, 2019; Crayne and Medeiros, 2021). These findings emphasize the need to explore the immense importance of wider exogenous factors (such as accountability) when theorizing processes as complex as decision-making under uncertainty and the effect of social power. While it is a staple finding in the field that power increases approach motivations and improves decision-making (Kang et al., 2015), this study questioned the universal positive and approach effects of power and instead found that those with power were more avoidant, and indeed found decisions harder, especially when making decisions they had experience with (domain-specific). This study thus challenges the linear conceptualization of approach-inhibition theories of social power and proposes that, under certain conditions, power can lead to FFFS/BIS activation and avoidance tendencies. This advances the need for future research that explores the conditions in which power leads to avoid, rather than approach tendencies. There are also several further questions to be explored. For example, recent research has shown that individual differences in personality characteristics (e.g., maximization) impact the degree to which decision-making is impacted by interventions (Shortland et al., 2021). As such, it is viable to propose that individual differences in certain key personality traits may moderate the effect of power on avoidance. Furthermore, it is also important to acknowledge the degree to which the relationship between power and avoidance may be cyclical. That is avoidance may lead to a decrease in how others in the organization perceive the individual, decreasing their power further and leading to more avoidance. Finally, it is important to consider how the role of power integrates with other known sources of avoidance. For example, previous research has highlighted the role of organizational culture and "career fear" (van den Heuvel et al., 2013). While this study highlights an important individual-level contribution to the tendency to make avoidant decisions, naturalistic research makes it evidently clear that avoidance is the result of a range of influences as the individual, cultural and environmental, level, and future research needs to further explore the interactions of these factors. That said, and despite these further theoretical questions, this research provided a critical addition to our understanding of the many (and not always positive) impacts of power on decision-making. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics statement The studies involving human participants were reviewed and approved by the University of Massachusetts Lowell. The patients/participants provided their written informed consent to participate in this study. Author contributions NS, MM, and NB: conceptualization, methodology, data curation, and writing original draft. LT: writing original draft, data curation, and formal analysis. LA: conceptualization, methodology, supervision, and review. JG: statistics. PM and CS: writing and editing and theorizing. All authors contributed to the article and approved the submitted version. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. References Aiken L. S. West S. G. Reno R. R. (1991). 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PMC10000296 | Front Microbiol Front Microbiol Front. Microbiol. Frontiers in Microbiology 1664-302X Frontiers Media S.A. 10.3389/fmicb.2022.1098133 Microbiology Original Research Real-time PCR has advantages over culture-based methods in identifying major airway bacterial pathogens in chronic obstructive pulmonary disease: Results from three clinical studies in Europe and North America Schoonbroodt Sonia 1 + Ichante Jean-Laurent 1 + Boffe Sophie 2 Devos Nathalie 1 Devaster Jeanne-Marie 1 Taddei Laura 3 Rondini Simona 3 Arora Ashwani Kumar 3 Pascal Thierry 2 Malvaux Ludovic 2 * 1GSK, Rixensart, Belgium 2GSK, Wavre, Belgium 3GSK, Siena, Italy Edited by: Thomas H. Hampton, Dartmouth College, United States Reviewed by: Lauren Hatfield, Manchester Metropolitan University, United Kingdom; Helen Gavillet, Manchester Metropolitan University, United Kingdom *Correspondence: Ludovic Malvaux, [email protected] +These authors have contributed equally to this work and share first authorship This article was submitted to Infectious Agents and Disease, a section of the journal Frontiers in Microbiology 24 2 2023 2022 13 109813314 11 2022 29 12 2022 Malvaux, Schoonbroodt, Ichante, Boffe, Devos, Devaster, Taddei, Rondini, Arora and Pascal, (c) 2023 GSK. 2023 Malvaux, Schoonbroodt, Ichante, Boffe, Devos, Devaster, Taddei, Rondini, Arora and Pascal, (c) 2023 GSK This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction We compared the performance of real-time PCR with culture-based methods for identifying bacteria in sputum samples from patients with chronic obstructive pulmonary disease (COPD) in three studies. Methods This was an exploratory analysis of sputum samples collected during an observational study of 127 patients (AERIS; NCT01360398), phase 2 study of 145 patients (NTHI-004; NCT02075541), and phase 2b study of 606 patients (NTHI-MCAT-002; NCT03281876). Bacteria were identified by culture-based microbiological methods in local laboratories using fresh samples or by real-time PCR in a central laboratory using frozen samples. Haemophilus influenzae positivity with culture was differentiated from H. haemolyticus positivity by microarray analysis or PCR. The feasibility of bacterial detection by culture-based methods on previously frozen samples was also examined in the NTHI-004 study. Results Bacterial detection results from both culture-based and PCR assays were available from 2,293 samples from AERIS, 974 from the NTHI-004 study, and 1736 from the NTHI-MCAT-002 study. Quantitative real-time PCR (qPCR) showed higher positivity rates than culture for H. influenzae (percentages for each study: 43.4% versus 26.2%, 47.1% versus 23.6%, 32.7% versus 10.4%) and Moraxella catarrhalis (12.9% versus 6.3%, 19.0% versus 6.0%, 15.5% versus 4.1%). In the NTHI-004 and NTHI-MCAT-002 studies, positivity rates were higher with qPCR for Streptococcus pneumoniae (15.6% versus 6.1%, 15.5% versus 3.8%); in AERIS, a lower rate with qPCR than with culture (11.0% versus 17.4%) was explained by misidentification of S. pseudopneumoniae/mitis isolates via conventional microbiological methods. Concordance analysis showed lowest overall agreement for H. influenzae (82.0%, 75.6%, 77.6%), due mainly to culture-negative/qPCR-positive samples, indicating lower sensitivity of the culture-based methods. The lowest positive agreement (culture-positive/qPCR-positive samples) was observed for S. pneumoniae (35.1%, 71.2%, 71.2%). Bacterial load values for each species showed a proportion of culture-negative samples with a load detected by qPCR; for some samples, the loads were in line with those observed in culture-positive samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples. Discussion Real-time PCR on frozen sputum samples has enhanced sensitivity and specificity over culture-based methods, supporting its use for the identification of common respiratory bacterial species in patients with COPD. bacterial identification culture PCR sensitivity Haemophilus influenzae Moraxella catarrhalis Streptococcus pneumoniae chronic obstructive pulmonary disease pmcIntroduction Chronic obstructive pulmonary disease (COPD) is a common condition characterized by persistent respiratory symptoms, often punctuated by acute exacerbations that can lead to hospitalization and a faster decline in lung function (Criner et al., 2015; Global Initiative for Chronic Obstructive Lung Disease, 2021). Different studies, including the observational Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study, have shown an association between exacerbation state and increased prevalence of airway bacteria, most commonly non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, with some reports of an association with Streptococcus pneumoniae also (Garcha et al., 2012; Molyneaux et al., 2013; Huang et al., 2014; Millares et al., 2014; Wang et al., 2015; Wilkinson et al., 2017; Jubinville et al., 2018; Mayhew et al., 2018; Weeks et al., 2021). In the AERIS study, changes in the yearly COPD exacerbation rate were associated with changes in H. influenzae colonization (Wilkinson et al., 2019a), and nearly all (99%) H. influenzae isolates were non-typeable (Wilkinson et al., 2017). A multi-component investigational vaccine was developed to reduce the frequency of acute exacerbations of COPD (AECOPD) associated with NTHi (Leroux-Roels et al., 2016), followed by a second related vaccine (NTHi-Mcat vaccine) to prevent NTHi-and M. catarrhalis-associated exacerbations (Van Damme et al., 2019). Both vaccines contain three conserved surface NTHi proteins, while the NTHi-Mcat vaccine also contains a surface protein from M. catarrhalis (Leroux-Roels et al., 2016; Van Damme et al., 2019). A phase 2 study of the NTHi vaccine (NTHI-004) and phase 2b study of the NTHi-Mcat vaccine (NTHI-MCAT-002) showed immunogenicity and no safety concerns when either vaccine was administered to patients with COPD (Wilkinson et al., 2019b; Andreas et al., 2022). In the NTHI-MCAT-002 study, while vaccination did not reduce the frequency of moderate/severe exacerbations, with no difference between groups in rate of AECOPD associated with NTHi or M. catarrhalis, observations suggested possible reductions in severe exacerbations and related hospitalizations in the vaccinated group versus placebo (Andreas et al., 2022). In the AERIS, NTHI-004, and NTHI-MCAT-002 studies, sputum samples were collected from patients at regular intervals and at exacerbation (Wilkinson et al., 2017, 2019b; Andreas et al., 2022). Bacteria in freshly collected sputum were identified in local laboratories using conventional culture-based microbiological methods that were not harmonized. In parallel, frozen dithiothreitol (DTT)-treated sputum samples were transported to a central laboratory and analyzed by real-time PCR assay. Various studies have shown that molecular techniques, such as PCR, have better specificity and sensitivity than conventional culture-dependent methods in the detection of airway bacteria in patients with COPD (Eser et al., 2012; Garcha et al., 2012; Bafadhel et al., 2015; Gadsby et al., 2015; Wilkinson et al., 2017). Also, culture-based methods require fresh samples and their reliability can be affected by antibiotic treatment (Oliver, 2010; Wu et al., 2014) as well as the microbiologist's skills in phenotypic identification methods. In contrast, a PCR assay can be used on frozen samples in a central location where it has been well characterized, thus avoiding the risk of variations in microbiological methods among individual local laboratories. We now report on the performance of the microbiological assays used in the detection of bacteria in sputum samples in the AERIS, NTHI-004, and NTHI-MCAT-002 studies (Wilkinson et al., 2017, 2019b; Andreas et al., 2022). Quantitative and qualitative H. influenzae, M. catarrhalis, and S. pneumoniae identification results obtained with real-time PCR are compared with those obtained with culture-based methods. Additionally, using data from the NTHI-004 study, we examine the feasibility of freezing sputum samples before bacterial detection by culture in a central laboratory. Qualitative Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes identification data by PCR assay are also assessed from the three studies. Figure 1 provides a plain language summary of the findings from these assessments. Figure 1 Plain language summary. Materials and methods Sputum sample collection and processing The sputum samples were collected in three clinical studies of adults with COPD: the prospective observational cohort study, AERIS, of 127 patients (NCT01360398; Wilkinson et al., 2017), the phase 2 placebo-controlled NTHI-004 study of an investigational NTHi vaccine in 145 patients (NCT02075541; Wilkinson et al., 2019b), and the phase 2b placebo-controlled NTHI-MCAT-002 study of an investigational NTHi-Mcat vaccine in 606 patients (NCT03281876; Andreas et al., 2022). The AERIS study was conducted in the United Kingdom between June 2011 and June 2014, the NTHI-004 study in the UK and Sweden between July 2014 and April 2017, and the NTHI-MCAT-002 study in Belgium, Canada, France, Germany, Italy, Spain, United Kingdom, and United States between November 2017 and March 2020. Study summaries are available 1 (study identifiers 114378, 200157, and 207489) and methods and results on primary and secondary endpoints of the studies have been published (Wilkinson et al., 2017; Mayhew et al., 2018; Osman et al., 2018; Wilkinson et al., 2019b; Malvisi et al., 2021; Andreas et al., 2022). Sputum samples were obtained by spontaneous expectoration or induced, as per the investigator's judgement, at regular intervals during each study and at each exacerbation visit, and were processed according to standard methods, as described previously (Wilkinson et al., 2017, 2019b; Andreas et al., 2022). An acute exacerbation was defined as worsening of at least two major symptoms (dyspnea, sputum volume, and sputum purulence) or worsening of at least one major symptom and one minor symptom (sore throat, cold symptoms, fever, increased cough, and increased wheeze) for at least two consecutive days. Culture-based bacteriological methods and confirmatory assays Freshly collected sputum samples were treated with DTT at 49 local microbiological laboratories associated with the clinical sites (one site for AERIS study, 15 for NTHI-004 study, and 67 for NTHI-MCAT-002 study). Bacterial species were identified by standard culture-based identification procedures (Murray et al., 2007), as summarized in Figure 2, and according to each local laboratory's routine methods, with minor adaptations (relating to, for example, the agar plate used for culture, sputum DTT pre-treatment, and semi-quantitative culture data reporting). Identification protocols included phenotypic characterization, semi-quantitative culture, and other methods such as Gram staining and biochemical methods. In the AERIS and NTHI-MCAT-002 studies, qualitative real-time PCR was used to further discriminate bacterial isolates of H. influenzae from H. haemolyticus by assessing the presence of two genes: P6 (outer membrane protein gene), which is conserved among H. influenzae and H. haemolyticus, and lgtC (lipo-oligosaccharide glycosyltransferase gene), which is ubiquitous in all H. influenzae but only 2% prevalent in H. haemolyticus (McCrea et al., 2008; Sandstedt et al., 2008; Abdeldaim et al., 2009). In the NTHI-004 study, culture plate sweeps were taken from presumptive H. influenzae-positive sputum in order to confirm H. influenzae positivity. This was part of an extended investigation of sputum sweep samples by Senti-HI molecular serotyping microarray analysis (data not shown) at BUGS Bioscience laboratory (London, United Kingdom). Culture plate sweeps from presumptive H. influenzae-positive sputum were stored in skim milk-tryptone-glucose-glycerol (STGG) medium (O'Brien et al., 2001; Kaijalainen et al., 2004) and genomic DNA extracted. Confirmation of species was based on the detection of species-specific gene targets for H. influenzae, in parallel with no detection of species-specific gene targets for eight other relevant Haemophilus species. Figure 2 Culture-based and PCR methods used in the three clinical studies (AERIS, NTHI-004, and NTHI-MCAT-002) to identify Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes. * Samples confirmed as H. influenzae positive after differentiation from other Haemophilus species (e.g., H. haemolyticus) by (NTHI-004 study) Senti-HI microarray analysis on stored H. influenzae sweep or (AERIS and NTHI-MCAT-002 studies) lgtC/P6 qualitative real-time PCR assay. algD, GDP mannose dehydrogenase encoding gene; CDS 23, coding sequence 23; clfA, clumping factor A encoding gene; copB, copB outer membrane protein encoding gene; DTT, dithiothreitol; h, hours; lgtC, lipo-oligosaccharide glycosyltransferase encoding gene; lytA, autolysin encoding gene; STGG, skim milk-tryptone-glucose-glycerol medium. In the NTHI-004 study, a fraction of all DTT-treated sputum samples was stored in STGG medium before freezing and was shipped to the central laboratory for bacterial identification using standard culture-based methods. Bacterial identification data generated using culture-based methods were qualitative (positive/negative). The bacterial load of H. influenzae, M. catarrhalis, and S. pneumoniae in cultured samples was estimated using a semi-quantitative quadrant assessment method (Murdoch et al., 2017) adapted according to local laboratory practices, using a '0, Few, 1+, 2+, 3+' scale, with '0' indicating absence and '3+' corresponding to the highest load (bacterial presence in at least three of four quadrants of the agar plate). The 'Few' category, which applied when only few, sparsely spread colonies were observed in any quadrant of the plate, was not recorded in the NTHI-004 study, according to the routine practices of the local laboratories. PCR identification methods Frozen aliquots of DTT-treated sputum samples were transported to the testing laboratory and analyzed by real-time PCR assay . The methods used for nucleic acid extraction and PCR are summarized in Table 1 and primers and probes sequences are provided in Supplementary Table 1. Table 1 Methods used for the triplex real-time PCR assays. A. Triplex quantitative real-time PCR (qPCR) assay to identify Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae Study AERIS NTHI-004 NTHI-MCAT-002 Nucleic acid extraction kit and protocol MagNA Pure 96 equipment (Roche) Kingfisher equipment (Life Technologies) MagNA Pure 96 equipment (Roche) MagNA Pure 96 DNA and Viral NA small volume kit (viral NA universal protocol) LSI MagVet Universal Isolation kit MagNA Pure 96 DNA and Viral NA large volume kit (pathogen universal 500 protocol) Real-time qPCR reagent Taqman Fast Advanced Multiplex Universal Master Mix (Life Technologies) H. influenzae target gene lgtC M. catarrhalis target gene copB S. pneumoniae target gene lytA Sputum-DTT input volume 200 ml 100 ml 500 ml Nucleic acid eluate volume 50 ml 80 ml 100 ml Nucleic acid volume input in qPCR reaction 2 ml 2 ml 2 ml Copies/qPCR to copies/ml conversion factor Copies/ml = Copies/qPCR * 125 Copies/ml = Copies/qPCR * 400 Copies/ml = Copies/qPCR * 667 Positivity cut-off (assay LOD) H. influenzae 2,000 copies/ml 16,400 copies/ml 1,561 copies/ml M. catarrhalis 15,000 copies/ml 44,800 copies/ml 927 copies/ml S. pneumoniae 12,875 copies/ml 12,400 copies/ml 1,161 copies/ml Testing laboratory DDL Diagnostic GSK Vaccines GSK Vaccines B. Triplex qualitative real-time PCR assay to identify Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes Study AERIS NTHI-004 NTHI-MCAT-002 Nucleic acid extraction kit and protocol MagNA Pure 96 equipment (Roche) Kingfisher equipment (Life Technologies) MagNA Pure 96 equipment (Roche) MagNA Pure 96 DNA and Viral NA small volume kit (viral NA universal protocol) LSI MagVet Universal Isolation Kit MagNA Pure 96 DNA and Viral NA large volume kit (pathogen universal 500 protocol) Real-time PCR reagent Taqman Fast Advanced Multiplex Universal Master Mix (Life Technologies) P. aeruginosa target gene algD S. aureus target gene clfA S. pyogenes target gene CDS 23 Sputum-DTT input volume 200 ml 100 ml 500 ml Nucleic acid eluate volume 50 ml 80 ml 100 ml Nucleic acid volume input in PCR reaction 2 ml 2 ml 2 ml Positivity cut-off (assay LOD)* P. aeruginosa 16,625 copies/ml 21,600 copies/ml 768 copies/ml S. aureus 17,500 copies/ml 20,000 copies/ml 1,108 copies/ml Testing laboratory DDL Diagnostic GSK Vaccines GSK Vaccines copB, copB outer membrane protein encoding gene; DTT, dithiothreitol; lgtC, lipo-oligosaccharide glycosyltransferase encoding gene; LOD, limit of detection; lytA, autolysin encoding gene. algD, GDP mannose dehydrogenase encoding gene; CDS 23, coding sequence 23; clfA, clumping factor A encoding gene; DTT, dithiothreitol; LOD, limit of detection. *S. pyogenes not detected in sputum samples. Two triplex real-time PCR assays were employed that were developed by GSK and characterized in the AERIS study by DDL Diagnostic Laboratory (Rijswijk, the Netherlands) and in the NTHI-004 and NTHI-MCAT-002 studies by the central GSK laboratory (Wavre, Belgium). Following total nucleic acid extraction (see Table 1), a quantitative real-time PCR (qPCR) assay (Andreas et al., 2022) amplified DNA fragments of H. influenzae, M. catarrhalis, and S. pneumoniae using the TaqMan Fast Advanced Master Mix kit (Life Technologies) on Viia7 or QuantStudio 7 equipment (Life Technologies). A second PCR assay was a qualitative assay that amplified P. aeruginosa, S. aureus, and S. pyogenes DNA using the same nucleic acids and the same PCR reagents and equipment (Life Technologies). The protocol for the second assay was essentially the same as for the first, with adaptation of the primers and probes sequences (Supplementary Table 1). For the qPCR assay, three sets of primers and probes were designed from the conserved region of lgtC for H. influenzae (McCrea et al., 2008), the outer membrane protein copB gene for M. catarrhalis (Greiner et al., 2003), and the autolysin A gene (lytA) for S. pneumoniae. The lytA primers and probe sequences corresponded to those used in the lytA-CDC assay (Carvalho et al., 2007). The presence of S. pyogenes, S. aureus, and P. aeruginosa was determined using a qualitative real-time triplex PCR assay targeting conserved regions of the coding sequence 23 gene (CDS23), the clumping factor A encoding gene (clfA), and the GDP mannose dehydrogenase encoding gene (algD), respectively. S. pyogenes was not detected in any of the sputum samples. PCR identification results were quantitative (copies/ml) or qualitative (positive/negative). Only qualitative data are available for P. aeruginosa and S. aureus. The sample was considered positive when the measured load was equal to or above the assay cut-off corresponding to the limit of detection (LOD) of the assay. LODs, expressed in copies/ml of DTT-treated sputum, were defined during characterization of the technical performance of the qPCR assay. Over time, there was re-assessment of some assay parameters, including LOD and quantitation limits, due to improvement of the methods (e.g., updated methods for nucleic acids extraction). There were consequent differences in LOD values between studies (see Table 1). The concentration of H. influenzae, M. catarrhalis, and S. pneumoniae DNA (bacterial load, copies/ml) in each sample was inferred from the calibration curve made from serial dilutions of a plasmid containing the sequences targeted by the assay and converted from copies/qPCR to copies/ml of DTT-treated sputum samples. The specificity of these assays was verified theoretically (i.e., bioinformatic analyses) and experimentally (on related and unrelated bacteria and viruses commonly found in respiratory samples). No significant signal above the assays positivity cut-offs was observed and the sequencing of the PCR products generated from sputum samples confirmed that amplified material corresponded accurately to the reference sequences of the targeted pathogens. Statistical analyses This technical comparison was an exploratory analysis of data from sputum samples taken during the AERIS study (Wilkinson et al., 2017), NTHI-004 study (Wilkinson et al., 2019b), and NTHI-MCAT-002 study (Andreas et al., 2022), regardless of sputum quality and per-protocol defined cohorts. Positivity rates and their 95% confidence intervals (CIs) were calculated for the results of each assay. Concordance and agreement analyses were conducted on the qualitative identification results from samples for which both culture-based and PCR assay results were available. Overall agreement, positive agreement, and negative agreement were calculated as described in the footnote to Table 2. Dissymmetry in the number of discordant samples was evaluated by McNemar's test. In the analysis of bacterial load, samples with qPCR values above 0 copies/ml were considered for median computation and were plotted as a function of semi-quantitative culture results. Table 2 Concordance analysis between bacterial pathogen identification results obtained by sputum culture and PCR assay (samples with both culture and PCR results). Number of samples Overall agreementa (%) Positive agreementb (%) Negative agreementc (%) P valued Pathogen Study Culture-negative, PCR-negative Culture-negative, PCR-positive Culture-positive, PCR-negative Culture-positive, PCR-positive Haemophilus influenzae e AERIS 1,173 367 9 538 81.98 98.35 76.17 <0.0001 NTHI-004 501 229 5 223 75.57 97.81 68.63 <0.0001 NTHI-MCAT-002 1,140 379 1 176 77.59 99.44 75.05 <0.0001 Moraxella catarrhalis AERIS 1,824 143 4 128 93.00 96.97 92.73 <0.0001 NTHI-004 773 127 2 55 86.52 96.49 85.89 <0.0001 NTHI-MCAT-002 1,462 201 4 68 88.18 94.44 87.91 <0.0001 Streptococcus pneumoniae AERIS 1,631 103 237 128 83.80 35.07 94.06 <0.0001 NTHI-004 790 108 17 42 86.94 71.19 87.97 <0.0001 NTHI-MCAT-002 1,445 221 19 47 86.14 71.21 86.73 <0.0001 Pseudomonas aeruginosa AERIS 1,967 35 10 113 97.88 91.87 98.25 0.0002 NTHI-004 918 13 4 21 98.22 84.00 98.60 0.0490 NTHI-MCAT-002 1,593 49 8 85 96.71 91.40 97.02 <0.0001 Staphylococcus aureus AERIS 1,993 23 33 76 97.36 69.72 98.86 0.2288 NTHI-004 874 46 10 26 94.14 72.22 95.00 <0.0001 NTHI-MCAT-002 1,517 108 26 85 92.28 76.58 93.35 <0.0001 a Calculated as [(Culture-positive, PCR-positive) + (Culture-negative, PCR-negative)] divided by [(Culture-positive, PCR-positive) + (Culture-negative, PCR-negative) + (Culture-positive, PCR-negative) + (Culture-negative, PCR-positive)]. b Calculated as (Culture-positive, PCR-positive) divided by [(Culture-positive, PCR-positive) + (Culture-positive, PCR-negative)]. c Calculated as (Culture-negative, PCR-negative) divided by [(Culture-negative, PCR-negative) + (Culture-negative, PCR-positive)]. d Difference between culture-negative/PCR-positive samples and culture-positive/PCR-negative samples: McNemar's test. e Samples confirmed as positive after differentiation from H. haemolyticus by Senti-HI microarray analysis or lgtC/P6 real-time PCR assay. Results Sampling The total number of sputum samples from which bacterial detection results were available from both culture-based and PCR assays were 2,293 sputum samples from 127 patients in the AERIS study (years 1 and 2), 974 sputum samples from the NTHI-004 study (488 from 73 patients who received the investigational NTHi vaccine and 486 from 72 patients in the placebo group), and 1736 sputum samples from the NTHI-MCAT-002 study (878 from 304 patients who received the NTHi-Mcat vaccine and 858 from 302 patients who received placebo). Bacterial identification For H. influenzae and M. catarrhalis in all three studies, and S. pneumoniae in the NTHI-004 and NTHI-MCAT-002 studies, concordance analysis showed overall agreement of culture and qPCR data was between 75 and 93% (Table 2). Overall agreements were mainly impacted by the low negative agreement. Indeed, more samples were positive when identification was performed using qPCR, with statistically significant (p < 0.0001) differences between positivity rates for samples assessed by culture versus those assessed by qPCR . In the concordance analysis, culture-negative/qPCR-positive results were associated with significant p-values (p < 0.0001; McNemar's test), indicating increased sensitivity with qPCR compared to culture-based methods for the three bacterial species (Table 2). Figure 3 Percentage of culture-positive sputum samples derived from freshly collected samples assessed in local laboratories (grey bars) and percentage of PCR-positive sputum samples derived from frozen samples and assessed centrally (light brown bars). 95% CI, 95% confidence interval; n, number of samples for which there were both valid culture and PCR results (POS/NEG) for each targeted pathogen. The concordance analysis also showed, for H. influenzae, M. catarrhalis, and S. pneumoniae, few culture-positive and qPCR-negative samples, apart from for S. pneumoniae in the AERIS study (Table 2). Moreover, the positivity rate for S. pneumoniae in the AERIS study was significantly higher (p < 0.0001) with culture identification than with qPCR . This discrepancy between culture and qPCR assay results observed with S. pneumoniae in the AERIS study was investigated further via various molecular techniques and mass spectrometry (see Supplementary material). This confirmed that the high rate of false-positive samples by culture-based methods was due to misidentification of samples containing Streptococcus pseudopneumoniae or Streptococcus mitis species. For P. aeruginosa, the positivity rate was significantly higher (p = 0.0049) with PCR than with culture in the NTHI-MCAT-002 study only, while for S. aureus, a statistically significant difference was only observed in the NTHI-004 study (p = 0.0002) and the NTHI-MCAT-002 study (p < 0.0001), with higher positivity rates with PCR . Concordance analysis showed overall agreement of culture and PCR data was between 92% and 98% (Table 2). The difference between culture-negative/PCR-positive samples and culture-positive/PCR-negative samples was statistically significant (p < 0.05; McNemar's test) in all three studies, apart from the discordant results for S. aureus in the AERIS study (Table 2). The NTHI-004 study also evaluated the feasibility of freezing sputum samples before bacterial detection by culture in a central laboratory. The comparison of two culture-based methods for identifying H. influenzae, M. catarrhalis, and S. pneumoniae showed lower positivity rates for STGG-frozen samples processed centrally than for fresh samples tested locally (Supplementary Table 2). Of fresh samples that tested H. influenzae-positive by culture, thawed frozen samples remained positive for 39.5% of samples and positive agreement was 47.1% for M. catarrhalis and 18.5% for S. pneumoniae (Supplementary Table 3). Bacterial load Bacterial load data generated by qPCR were plotted against the semi-quantitative results from culture-based methods for H. influenzae, M. catarrhalis, and S. pneumoniae. Figure 4 shows data for samples with qPCR loads above >0 copy/reaction and associated with a semi-quantitative culture result. There was a positive trend between the qPCR load and semi-quantitative culture results. For each species, the median load calculated by qPCR in sputum samples was higher in culture-positive samples than in culture-negative samples . Most culture-negative samples were associated with null bacterial loads by qPCR . For the AERIS study, of 1,540, 1,967, and 1,734 samples that were culture-negative for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively, 1,017 (66.0%), 1,678 (85.3%), and 1,556 (89.7%) had null bacterial loads by qPCR. For the NTHI-004 study, of 730, 900, and 898 samples that were culture-negative for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively, 463 (63.4%), 733 (81.4%), and 769 (85.6%) had null bacterial loads by qPCR. Similarly, for the NTHI-MCAT-002 study, of 1,519, 1,663, and 1,666 culture-negative samples for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively, 1,015 (66.8%), 1,370 (82.4%), and 1,354 (81.3%) had null bacterial loads by qPCR. Therefore, across all three studies, 33-37% (H. influenzae), 15-19% (M. catarrhalis), and 10-19% (S. pneumoniae) of culture-negative samples were detected by qPCR assay (below or above the positivity cut-off), with loads for some samples in line with those observed in culture-positive samples . Figure 4 Box and dot plots of bacterial load results by quantitative real-time PCR (qPCR) as a function of semi-quantitative culture results. Median, first and third quartiles, and minimum and maximum data shown. a Culture-positive samples confirmed by Senti-HI microarray or lgtC/P6 real-time PCR assay. b Samples with qPCR loads above >0 copy/reaction and associated with a semi-quantitative culture result. See Table 1 for qPCR positivity cut-offs for H. influenzae, M. catarrhalis, and S. pneumoniae. Bacterial load in cultured samples estimated using the quadrant assessment method, according to a '0, Few, 1+, 2+, 3+' scale, with '0' indicating absence and '3+' corresponding to the highest load. 'Few' category not recorded in NTHI-004 study. Discussion We compared the performance of culture-based and PCR assays in identifying bacterial airway pathogens in sputum samples taken in three clinical studies of patients with COPD. In each study, two triplex real-time PCR assays were used, developed by GSK: a qPCR assay to detect and quantify H. influenzae, M. catarrhalis, and S. pneumoniae from sputum total nucleic acids, involving hydrolysis probes to maximize specificity, and a qualitative PCR assay to detect P. aeruginosa, S. aureus, and S. pyogenes. S. pyogenes was not identified in sputum samples from any of the studies. The three studies were conducted over the period 2011 to 2020, during which time the PCR assays were improved, such as in extraction methods for nucleic acids, leading to adjustments in LOD. Our results show that real-time qPCR has higher specificity and sensitivity than culture-based methods for the detection of the most frequent bacterial species identified: H. influenzae, M. catarrhalis, and S. pneumoniae. The bacterial load analyses for these three species showed that some samples negative by culture contained a significant amount (over 10 million copies/ml) of bacterial DNA. Moreover, for P. aeruginosa and S. aureus, analysis of over 1,700 samples in the NTHI-MCAT-002 study showed significantly higher positivity rates with PCR than with culture-based detection methods for both species, although in the other two studies the difference was only significant for S. aureus in the NTHI-004 study. Overall, however, these data confirm previous reports of higher sensitivity with the PCR assay than with culture-based methods not only in COPD but also other conditions, such as otitis media and cystic fibrosis (Eser et al., 2012; Garcha et al., 2012; Bafadhel et al., 2015; Gadsby et al., 2015; Wilkinson et al., 2017; Gavillet et al., 2022). For example, one study of the detection of P. aeruginosa and S. aureus in cystic fibrosis found significantly lower detection of both lung pathogens by culture, which often did not detect either pathogen despite being found repeatedly by qPCR (Gavillet et al., 2022). In our study, qPCR positivity rates were around two-to four-fold higher for H. influenzae and M. catarrhalis in all three studies and for S. pneumoniae in the NTHI-004 and NTHI-MCAT-002 studies. In the concordance analysis, the lowest percentage positive agreement was for S. pneumoniae in the AERIS study (35%), reflecting the proportion of qPCR-negative samples among the culture-positive ones. Further analysis of this discrepant result led to the re-identification of a significant number of isolates, initially attributed to be S. pneumoniae isolates, as S. pseudopneumoniae or S. mitis by molecular techniques. The reason for this observation in the AERIS study may be related to characteristics of locally circulating strains or the specificity of the culture methods used to identify S. pneumoniae in the AERIS study laboratory; positive agreement in the other two studies was 71%. This suggests the culture-based method may have, in some settings, low specificity for S. pneumoniae. A lack of specificity with culture-based methods is also demonstrated by the need to discriminate H. influenzae from H. haemolyticus isolates in presumptive H. influenzae-positive samples by using molecular methods (Murphy et al., 2007), as confirmed by qPCR or microarray in the three studies analyzed. Of the bacterial species assessed, the concordance analysis showed the lowest percentage overall agreement (76-82%) for H. influenzae (confirmed samples), due mainly to samples that were negative with culture-based detection but positive with qPCR. However, the presence of culture-negative samples associated with high bacterial DNA loads suggests this may have been partly due to the presence of non-culturable but viable bacteria (Oliver, 2010) or poor sensitivity of the culture method used. For example, use of bacitracin agar increases identification rates for H. influenzae (Harris et al., 2017) but this was not used in all laboratories. There is also a possibility that, although patients were instructed not to take an antibiotic before site visits, antibiotic treatment before sputum collection could have had an impact on the bacterial culture results (Brown and Spiegel, 2019). In this case, bacteria may not have been capable of growing on an agar plate but would have been detected by real-time PCR. Our data suggest important advantages related to the specificity and sensitivity of real-time PCR over conventional culture-based methods for the assessment of airway bacteria in patients with COPD. Molecular assays can be performed on frozen sputum samples (Zhao et al., 2011; Cuthbertson et al., 2014), whereas culture needs to be done shortly after sputum collection to ensure sample integrity and bacteria viability (Baron et al., 2013). Frozen samples can be processed in a central laboratory with a well characterized PCR-based method, while fresh samples processed via conventional microbiological methods may require multiple local laboratories to avoid loss of viability. These local laboratories may not use exactly the same methods , affecting the consistency of results (Hogardt et al., 2009). Culture of freeze/thawed samples in a central laboratory was examined in the NTHI-004 study as an option to avoid unharmonized methods across local laboratories. This analysis of the impact of freezing sputum samples before species identification by culture-based methods used STGG as storage medium since preserved H. influenzae, M. catarrhalis, and S. pneumoniae isolate viability had been reported with its use (Kaijalainen et al., 2004). However, the culture-positivity rate in STGG-frozen sputum samples was only around 50% or less of that in fresh samples, showing this is not a feasible option for evaluating sputum samples, thus providing further support for PCR testing of frozen samples in a central laboratory. The ability to freeze sputum samples is a particular advantage in phase 3 clinical trials of COPD patients, which generally require large numbers of sites to enroll a sufficient number of patients (Tashkin et al., 2008; Wedzicha et al., 2008; Calverley et al., 2009; Albert et al., 2011; Wedzicha et al., 2013; Pascoe et al., 2016). However, central analysis of frozen samples is associated with additional shipment costs and there is a risk of inappropriate sample management during the transport or freezing procedure, although there is also a management risk associated with fresh samples, for example, if not processed within the appropriate time window. Additionally, antibiotic usage before sputum sample collection can have an impact on the reliability of bacterial data obtained by culture (Wu et al., 2014; Mammen and Sethi, 2016; Jacobs et al., 2018), and the identification of pathogens by culture can be complicated by species overgrowth and contamination by commensal bacteria, while PCR allows direct species detection irrespective of these circumstances (Scoleri et al., 2016). PCR also has many advantages in terms of easy evaluation of bacterial load, it is relatively inexpensive, and it can be used to process more samples simultaneously than culture. These advantages assume the PCR assay has been appropriately designed (with highly specific oligonucleotide selection) and well characterized in terms of assay parameters, including LOD and quantitation limits, as was done for the PCR assays used in the AERIS, NTHI-004, and NTHI-MCAT-002 studies. A major strength of these analyses is the large number (totaling 5,003) and multinational origin (Europe and North America) of sputum samples assessed for bacterial detection results from both culture-based and PCR assays. Also, the triplex real-time PCR assays used in each study were essentially the same, with any differences related to improvements made over time. The results of these analyses are limited by the possibility of false-positives resulting from the detection of low amounts of DNA, associated with dead bacteria, by qPCR. However, this was mitigated in these studies by using a LOD for each qPCR target as positivity cut-off (i.e., a sample was considered positive for a pathogen by qPCR if the observed load is equal to or above the corresponding LOD). We found many culture-and PCR-negative samples had PCR signals detected below the positivity cut-off, suggesting that using a PCR positivity cut-off is meaningful to limit the proportion of false-positives. Although qPCR can detect both viable and non-viable bacteria (Rudi et al., 2005), we found the bacterial loads measured by qPCR generally mirrored those measured by culture. Nevertheless, it would have been of interest to determine if samples found negative with culture-based techniques but positive on qPCR assay contained viable bacteria that were not culturable, as reported in other studies (Stenfors and Raisanen, 1992; Oliver, 2010; Lee and Bae, 2018), as well as the rate of non-viable bacteria present in samples recorded as qPCR-positive. In conclusion, these results encourage the use of real-time PCR assays for the identification of respiratory bacteria in patients with COPD. PCR assay addresses some of the limitations of conventional culture-based methods in terms of specificity and sensitivity in detecting bacterial infection. PCR has additional advantages, including the ability to be performed in a centralized location on frozen samples and the capacity to detect viable but non-culturable bacteria. This supports the use of well characterized molecular methods for the identification and quantification of bacteria in future studies of patients with COPD, especially when working in a multicenter setting requiring sample testing in multiple laboratories. Data availability statement The datasets presented in this article are not readily available because anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Ethics statement The studies involving human participants were reviewed and approved by the South West Hampshire Research Ethics Committee (Research Ethics Committee reference number: 11/H0502/9) for the AERIS study; the Southampton and South West Hampshire Research Ethics Committee, United Kingdom, and Regional Research Ethics Committee, Gothenburg, Sweden for the NTHI-004 study; the ethics committee of each participating center for the NTHI-MCAT-002 study. The patients/participants provided their written informed consent to participate in this study. Author contributions SS, ND, J-MD, LT, SR, AKA, TP, and LM were involved in analysis conception and design. SB, ND, J-MD, LT, SR, AKA, TP, and LM were involved in acquisition and generation of data. All authors performed the data analysis and/or data interpretation. ND and LM provided materials for the analyses. All authors contributed to the article and approved the submitted version. Funding GlaxoSmithKline Biologicals SA funded the AERIS, NTHI-004, and NTHI-MCAT-002 clinical studies and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript. Conflict of interest SS, J-LI, SB, ND, J-MD, LT, SR, AKA, TP, and LM are employed by GSK. SS, ND, J-MD, LT, TP, and LM hold shares in GSK. J-MD is also a designated inventor on patents owned by GSK. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. The authors thank all participants, all members of the Clinical Laboratory Sciences teams involved in the generation of the data, and all external investigators and laboratory personal who generated the microbiological data from the studies AERIS (NCT01360398), NTHI-004 (NCT02075541), and NTHI-MCAT-002 (NCT03281876). We thank Jason Hinds (St George's, University of London, and BUGS Bioscience) for the development of the Senti-HI microarray tool and testing of the NTHI-004 study samples, and for permission to use the Senti-HI microarray data. We also thank Marie-Cecile Mortier (GSK) for her bioinformatics support. The authors also thank Business & Decision Life Sciences platform for editorial assistance, manuscript coordination, and writing support, on behalf of GSK. Joanne Knowles (independent medical writer, on behalf of GSK) provided medical writing support. Supplementary material The Supplementary material for this article can be found online at: Click here for additional data file. Abbreviations AECOPD acute exacerbations of chronic obstructive pulmonary disease AERIS Acute Exacerbation and Respiratory InfectionS in COPD algD GDP mannose dehydrogenase encoding gene CDS 23 coding sequence 23 gene clfA clumping factor A encoding gene copB copB outer membrane protein encoding gene COPD chronic obstructive pulmonary disease DTT dithiothreitol lgtC lipo-oligosaccharide glycosyltransferase encoding gene LOD limit of detection lytA autolysin encoding gene Mcat Moraxella catarrhalis NTHi non-typeable Haemophilus influenzae PCR Polymerase Chain Reaction qPCR quantitative real-time PCR STGG skim milk-tryptone-glucose-glycerol 1www.gsk-studyregister.com References Abdeldaim G. M. Stralin K. Kirsebom L. A. Olcen P. Blomberg J. Herrmann B. (2009). 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PMC10000297 | Front Psychol Front Psychol Front. Psychol. Frontiers in Psychology 1664-1078 Frontiers Media S.A. 10.3389/fpsyg.2023.1113143 Psychology Original Research A cross-linguistic, sound symbolic relationship between labial consonants, voiced plosives, and Pokemon friendship Kilpatrick Alexander 1 * Cwiek Aleksandra 2 Lewis Eleanor 3 Kawahara Shigeto 4 1Nagoya University of Commerce and Business, Nagoya, Japan 2Leibniz Center for General Linguistics (ZAS), Berlin, Germany 3Independent Researcher, Melbourne, VIC, Australia 4Keio University, Minato, Japan Edited by: Pia Knoeferle, Humboldt University of Berlin, Germany Reviewed by: Elena Zaretsky, Clark University, United States; Hideyuki Tanaka, Tokyo University of Agriculture and Technology, Koganei, Japan; Elisa Scerrati, University of Modena and Reggio Emilia, Italy *Correspondence: Alexander Kilpatrick, [email protected] This article was submitted to Language Sciences, a section of the journal Frontiers in Psychology 24 2 2023 2023 14 111314301 12 2022 07 2 2023 Copyright (c) 2023 Kilpatrick, Cwiek, Lewis and Kawahara. 2023 Kilpatrick, Cwiek, Lewis and Kawahara This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction This paper presents a cross-linguistic study of sound symbolism, analysing a six-language corpus of all Pokemon names available as of January 2022. It tests the effects of labial consonants and voiced plosives on a Pokemon attribute known as friendship. Friendship is a mechanic in the core series of Pokemon video games that arguably reflects how friendly each Pokemon is. Method Poisson regression is used to examine the relationship between the friendship mechanic and the number of times /p/, /b/, /d/, /m/, /g/, and /w/ occur in the names of English, Japanese, Korean, Chinese, German, and French Pokemon. Results Bilabial plosives, /p/ and /b/, typically represent high friendship values in Pokemon names while /m/, /d/, and /g/ typically represent low friendship values. No association is found for /w/ in any language. Discussion Many of the previously known cases of cross-linguistic sound symbolic patterns can be explained by the relationship between how sounds in words are articulated and the physical qualities of the referents. This study, however, builds upon the underexplored relationship between sound symbolism and abstract qualities. cross linguistic analysis Pokemon sound symbolism Poisson regression analysis iconicity Japan Society for the Promotion of Science 10.13039/501100001691 pmc1. Introduction There has been a growing interest in the exploration of sound symbolism in natural language. Studies that explore this subject typically find that the physical properties of entities are reflected in the speech sounds of their names (Westermann, 1937; Berlin, 1992, 2006; Shinohara and Kawahara, 2010; Sidhu and Pexman, 2018; Davis et al., 2019). These findings challenge one of the principles of the linguistic sign put forth by Saussure (1916) which assumes that the relationship between the form of the linguistic sign and its meaning is arbitrary. However, Sapir's (1929) seminal experimental study on sound symbolism showed that English speakers tend to associate the open vowel /a/ with larger objects and the closed vowel /i/ with smaller objects. Arguably, Sapir's findings reflect a physical, sensory-based relationship between the object and the sound; open (i.e., lower) vowels reflect largeness because the oral aperture must be larger to articulate them, in comparison to closed (i.e., higher) vowels (Kawahara, 2021). The current paper contributes to the growing literature on the relationships between abstract qualities and sound symbolism. It examines sound symbolic relationships in the names of North American English (hereafter: English), Japanese, South Korean (hereafter: Korean), Mandarin Chinese (hereafter: Chinese), Standard German (hereafter: German), and European French (hereafter: French) Pokemon. More specifically, it examines a Pokemon attribute known as friendship in English and natsuki-do [degree of attachment] in Japanese, demonstrating a systematic relationship between this video game metric and the sounds that make up 5,388 video game character names. 1.1. Sound symbolism Sound symbolism, the correspondence between sounds and meaning, has been a popular scholarly area of enquiry since the early 20th century (e.g., Wells, 1919; Sapir, 1929; Newman, 1933) and quantitative research has revealed many sound symbolic patterns, several of which hold cross-linguistically. For example, voiced obstruents have been found to be judged as suitable for the names of larger or heavier objects (Newman, 1933). This pattern has been observed in English (Newman, 1933), Japanese (Hamano, 1986; Shinohara and Kawahara, 2010; Kawahara and Shinohara, 2012), and Chinese (Shinohara and Kawahara, 2010). Alongside size, shape has also been found to be reflected sound symbolically. Kohler (1929) was the first to notice that angular objects tend to be associated with words like takete while round objects tend to be associated with words like maluma, the effect subsequently replicated with kiki and bouba, respectively (Ramachandran and Hubbard, 2001). This cross-modal correspondence between sound and shape is known to hold across different languages (Bremner et al., 2013; Chen et al., 2016; Cwiek et al., 2022, but see Rogers and Ross, 1975; Styles and Gawne, 2017). It is yet unclear, whether consonants or vowels play the main role in the kiki/bouba effect, or whether it relies on their additive symbolic relation (Nielsen and Rendall, 2013; Fort et al., 2015; McCormick et al., 2015). Most recently, Fort and Schwartz (2022) showed that the effect lies in the physical properties of shapes that result in acoustic patterns corresponding to the respective nonce words. Some scholars have also argued that this particular shape-sound relationship may be relevant for the acquisition and development of language (Maurer et al., 2006; Imai and Kita, 2014; Cwiek et al., 2022). Several theories have been presented to explain the relationship between sounds and physical properties. Regarding the size-sound relationship, Ohala (1994) proposed the underlying mechanism to be the "frequency code". In the natural environment, animals that are larger naturally produce a lower fundamental frequency (F0). In turn, lower F0 is perceived as a signal of largeness, and therefore threat and dominance, while higher F0 is perceived as a signal of smallness that stands for the lack of threat and friendliness. It has been shown that some animals use this correspondence as a deceiving mechanism in order to signal hostility (Morton, 1994; Bee, 2000). Ohala (1994, p. 335) also refers to the second formant frequency (F2) as a possible cause for this effect in sound symbolism. F2 frequency has been found to iconically express deictic relations (Johansson and Zlatev, 1970; Ultan, 1978; Woodworth, 1991; Traunmuller, 1994) such that a proximal reference is conveyed by vowels with higher F2, such as [i], and distal by vowels with low F2, such as [a] and [o]. Johansson and Zlatev (1970), after Traunmuller (1994), propose that the proximal-distal and small-large oppositions are based on the iconic similarity between mappings; i.e., a small size corresponds to a small distance, and a large size to a large distance. Thus, the correspondences described above rely on iconicity - a relationship between the linguistic form and meaning (e.g., Perniss and Vigliocco, 2014). They are not restricted to speech sounds but extend to other linguistic domains, such as prosody. It has been shown that listeners infer information regarding size (Shintel et al., 2014) or movement (Shintel and Nusbaum, 2007) of an entity from prosodic information. Higher pitch represents smaller entities, and faster speech rate represents entities in faster motion. These mechanisms are also conveyed in speech production. It has been shown that speakers reliably use higher pitch to convey "smaller" domains (Nygaard et al., 2009; Perlman et al., 2015), or exhibit higher speech rate when talking about fast events (Shintel et al., 2006; Perlman, 2010; Perlman et al., 2015). Some aspects of iconic prosody can be transferred to the written domain. Fuchs et al. (2019) investigated adjective antonym pairs, such as short/long, tiny/huge, and fast/slow, in an English blogger corpus. They found that the adjectives belonging to an iconically "larger" domain exhibit letter replications more often than the adjectives that belong to the "smaller" domain. Therefore, it seems that, iconically, the amount of the meaning can be expressed with the amount of sounds. Cross-linguistic iconic coding principles may be natural tendencies to express meanings with sounds that correspond to the physical nature of entities. Human languages are produced by a shared physiology, so it makes sense that we find cross-linguistic patterns whereby large objects are represented by large (or more) sounds and round objects are represented by sounds that are produced with lip rounding gestures. Regarding the expression of size, Winter and Perlman (2021) found that, while general vocabulary of English may not appear to show sound-symbolic patterns in its entirety, its specific subset, namely size adjectives, does so. In English size adjectives, /I/, /i/, /a/, and /t/ are especially suggestive of size - /a/ is more likely to occur in large adjectives, whereas the phonemes /I/, /i/, and /t/ are more likely to occur in small adjectives. For example, words like tiny, itsy-bitsy, and large adhere to this rule, although words like big and small are exceptions. In a study regarding the expression of shape, Sidhu et al. (2021) examined 1,757 English singular object nouns in the context of the maluma/takete effect (also known as kiki/bouba, see above). They found that the English lexicon carries sound-symbolic information such that phonemes associated with roundness are more likely to be found in names for round objects, and conversely "spiky" phonemes are more common in names for spiky objects (Fort and Schwartz, 2022). The correspondences between sounds and certain properties that involve a physical representation, such as size or shape, are perhaps the most apparent to us at the first sight. However, those immediate analogies can extend to relationships between speech sounds and more abstract qualities such as politeness (Winter et al., 2021; Brown et al., 2022), humour (Westbury and Hollis, 2019; Dingemanse and Thompson, 2020), or rudeness (Aryani et al., 2018). For example, studies have shown that human languages signal emotion via sound symbolism. Adelman et al. (2018) examined word-initial phonemes in English, Spanish, Dutch, German, and Polish and found that across languages, the first phoneme in each word is a significant predictor of emotional valence. They also found that phonemes that were uttered faster tended to convey danger, proposing that emotional sound symbolism is an evolutionary adaptation in humans, akin to alarm calls found in animal communication systems. Perhaps more striking examples of abstract qualities and sound symbolism come from marketing research, where sound symbolism is used to explore possibilities for enhancing the branding strategy (Klink, 2000, 2001, 2003; Pathak et al., 2020, 2022 to name a few). Klink (2000) conducted a comprehensive study comparing word pairs with contrasting segments and their effect on various physical and abstract qualities. The result suggests that native speakers of American English perceive front vowels not only as smaller or faster, but, e.g., also as more feminine, friendlier, or prettier. Except for femininity, these findings echo previous results by Fonagy (1963). As mentioned before, all those abstract qualities seem to be extensions of the basic principles, the immediate physical relationships. These relationships suggest that friendliness is connected with, e.g., high-frequency sounds (Morton, 1977; Ohala, 1994). Bridging the way towards the main motivation of the current study, previous studies on sound symbolism suggest that in Japanese, voiced obstruents tend to be associated with negative images (Hamano, 1986), while bilabial consonants are often associated with infancy (Kumagai and Kawahara, 2017; Kumagai, 2020). The latter finding is likely grounded in speech development. Babies use their lips to suck milk, and as such, they are a highly relevant organ for them; as a result, labials are among the very first consonants they produce (MacNeilage and Davis, 2000). This finding motivated a study by Uno et al. (2020) which explored sound symbolism in names of villainous and non-villainous characters. They used a corpus of the names of English Disney characters and the names of Japanese Pokemon. Pokemon have associated "types" and Uno et al. used "fairy type" as a proxy for non-villainous and "dark type" (in Japanese aku-taipu [evil type]) as a proxy for villainous. In a similar analysis as is found in the present study, they found that across both English and Japanese, voiced obstruents were associated with villainous names, and bilabial consonants were associated with non-villainous names. Motivated by the findings of these previous studies (Hamano, 1986; Kumagai and Kawahara, 2017; Kumagai, 2020; Uno et al., 2020, and others), the current study examines the sound symbolic properties of labial consonants and voiced obstruents. We take the immediate physical relationship and explore the extension of this relationship onto the abstract quality of friendliness in the names of Pokemon. 1.2. Pokemonastics Pokemon--also known as Pocket Monsters in Japan--is a Japanese media franchise centered on fictional monsters called Pokemon. Human characters in the franchise--known as trainers--catch and train Pokemon to battle with other Pokemon trainers for sport. The franchise began as a video game which soon developed into a mixed media empire. In the video game world, Pokemon have attributes that are expressed as numerical values. Pokemonastics is a relatively new field of research (Kawahara et al., 2018 et seq.) that examines sound symbolic relationships between the names of Pokemon and these attributes. Pokemonastic studies have some advantages over natural language studies and may uncover interesting cross-linguistic, sound symbolic relationships that would otherwise remain unobserved. Pokemon has been translated into many different languages, and while names change, Pokemon imagery and attributes remain stable. For example, the Pokemon known as Bulbasaur in English, is known as Miaowazhongzi in Chinese, and while they have different names, all other attributes and images remain the same. Cross-linguistic Pokemonastic studies therefore do not have to deal with issues pertaining to lexical semantics or polysemy that natural language studies may encounter (see Kawahara and Breiss (2021) for detailed discussion on this point). Initially, Pokemonastic studies focused on Japanese Pokemon names and found that features such as the number of voiced obstruents and name length reflected Pokemon attributes such as increased size and strength parameters (Kawahara et al., 2018). These studies have since been expanded to examine Pokemon names cross-linguistically to determine whether the same patterns exist across languages. In one such study, Shih et al. (2018) found that increased name length represented increased size, power, and evolution level not only in Japanese but also in English Pokemon. As Pokemon battle, they gain experience, and once they have gained enough experience, their level, and attributes increase. Many Pokemon have the option to evolve once they have attained a certain level which typically results in increased size and combat ability. Given that size, power, and evolution level are related, this finding can arguably be attributed to the iconicity of quantity (Haiman, 1980)--whereby larger entities are expressed by longer words as both strength and size (Shih et al., 2018) and evolution level can be symbolically expressed in terms of the length of Pokemon names (Kawahara and Moore, 2021). An interesting hypothesis that has arisen from Pokemonastic studies is that elements of sound symbolism in human languages may reflect attributes that are crucial to evolutionary survival (Shih et al., 2018; Uno et al., 2020). Pokemon attributes that reflect survivability--such as size and combat parameters--seem to be robustly reflected sound symbolically in Pokemon names while parameters that have little effect on survivability--such as gender distribution--are not. While in the real world, gender might predict combativeness, size, and physical strength, the gender mechanic in the video games has little in-game effect other than determining suitable partners in Pokemon breeding (Bulbagarden, 2004). Although not explicitly stated by Shih et al., this suggests that elements of sound symbolism relating to survivability can be innate (Perniss et al., 2010), presumably because they are evolutionarily beneficial. This proposal raises the possibility that human language evolved rather as a multimodal than a purely gestural system. Arguments for and against this proposal are presented in Kendon (2017) and Tomasello (2008) respectively (see also Perlman, 2017; Frohlich et al., 2019; Cwiek et al., 2021). Indeed, several recent studies point to the importance of multimodality in the emergence of language (Macuch Silva et al., 2020; Nolle et al., 2020). This is one of the reasons why it is important to explore sound symbolic patterns that reflect abstract qualities because cross-linguistic patterns that reflect physicality can be explained by natural and iconic relationships between sounds and objects, but when a quality has no physical representation, this explanation cannot hold (Lupyan and Winter, 2018). In order to contribute to addressing this general question, the present study seeks to test sound symbolic relationships pertaining to Pokemon friendship. This is with a caveat in mind that whether or not friendship is an abstract quality is debatable given that friendship in the Pokemon universe may be interpreted as a lack of threat or a lack of dominance which are conceptualized as concrete qualities in the frequency code hypothesis (Ohala, 1994). The present study examines a previously unexplored feature of Pokemon in Pokemonastics studies known as friendship. Friendship was first introduced in Pokemon Yellow, an enhanced version of the first generation of the core series of Pokemon video games, where it was only applied to the player's starter Pokemon. From the second generation onwards, all Pokemon had friendship as an attribute; however, in the second generation of the core series of video games, friendship was known as loyalty. Friendship has also been known as tame in Pokemon Stadium 2, friendliness in Pokemon XD: Gale of Darkness, and is often referred to as happiness by the gaming community. A second attribute known as affection in English or nakayoshi-do "degree of closeness" in Japanese was introduced in the sixth generation of the core video games, but this attribute was integrated into friendship in the eighth generation. The friendship level is expressed as a value ranging from 0-255. Each Pokemon has a default level of friendship, and in the following, we refer to this value as base friendship. Base friendship is the friendship value that each Pokemon has when it is first encountered by the player. Prior to generation 8 of the core series of video games, most Pokemon had a base friendship of 70; however, this was reduced to 50 for most Pokemon when affection was integrated into friendship. The present study uses the most recent base friendship values obtained from Bulbagarden (2004). Applying real-world meaning to friendship can be difficult because friendship has many different in-game effects. Friendship affects the base power of certain attacks, whether a Pokemon may evolve, non-player character interactions, and access to certain areas in the game world. If a trainer treats their Pokemon well (such as healing it during battle) the friendship value increases; on the other hand, if they treat their Pokemon poorly (such as making it battle until it loses consciousness), the value decreases. Pokemon can be traded between players and when a Pokemon is traded, all its attributes remain the same except for its friendship attribute which reverts to base, i.e., default friendship mentioned above, unless it is being traded back to a previous owner. Base friendship may therefore be considered a metric that relativises how naturally friendly each Pokemon is because it reflects how quickly Pokemon become attached to their trainers. Alternately, base friendship may be considered a reflection of how naturally happy each Pokemon is because those events that affect friendship would also affect mood. Yet another interpretation is that base friendship reflects how tame each Pokemon is because friendship affects how well Pokemon follow commands by raising the base power of certain moves. A common thread that runs through each of these interpretations is that base friendship reflects how threatening each Pokemon is to the player character because entities that are friendly, happy, and tame are less threatening than those that are not. These reasons taken together motivate using the base friendship metric as a baseline to study the sound-symbolic expression of natural friendliness of Pokemon. 1.3. Specific hypotheses tested The present study uses phoneme frequency in Pokemon names as a predictor of base friendship. It tests the following hypotheses: Labial consonants (/p/, /m/, and /w/1) will occur more frequently in the names of Pokemon with high base friendship values. Voiced obstruents (/d/ and /g/) will occur more frequently in the names of Pokemon with low base friendship values. Given that /b/ is both a bilabial consonant and a voiced obstruent, we make no prediction as to its relationship with base friendship. The first hypothesis is motivated by the findings of studies that show a relationship between labial sounds and infancy. Labials are among the very first sounds produced by infants (MacNeilage and Davis, 2000), which may motivate our association of those sounds with baby-like features (Kumagai and Kawahara, 2017) and images of softness and cuteness (Kumagai, 2020). Pokemon with high friendship values--much like infants--are non-threatening, and labial sounds may be a way of communicating this. The second hypothesis stems from the findings of Uno et al. (2020), which shows that voiced obstruents were predictors to villainy. Numerous studies have also shown that voiced obstruents have a systematic relationship with size, whereby objects with voiced obstruents in their name are more likely to be larger (Newman, 1933; Hamano, 1986; Shinohara and Kawahara, 2010; Kawahara and Shinohara, 2012). Villainous and large objects are more threatening than non-villainous and small objects so much like the way that bilabial consonants may communicate that an object is non-threatening, voiced obstruents may communicate danger. The voiced bilabial plosive/b/, is a special case because it is both a labial consonant and a voiced obstruent, so it is unclear whether it will be associated with high/low base friendship. 2. Materials and methods All data and code for this study are available under the following OSF repository: The data for this study was extracted from the website Bulbagarden (2004). Bulbapedia provides names for Pokemon in many languages; however, the present study only examines those languages that have been incorporated into the main content spaces (mainspaced, in the parlance of the website) as of January 2022. Mainspacing is used as quality control by the editors of the website; once an article has been mainspaced, it is considered complete. Only English, Japanese, Chinese, Korean, German, and French Pokemon tables have been mainspaced. The following analysis is conducted on a phoneme count of the labial consonants, /p/, /b/, /m/, and /w/, and the voiced plosives, /b/, /d/, and /g/. The phoneme count was conducted by individuals with training in phonology and/or phonetics who were either native speakers or knowledgeable of the phonology of the languages in question. None of the individuals who conducted the phoneme counts consider themselves familiar with all generations of Pokemon, so the analyses were not based on existing knowledge about Pokemon. For Japanese, Korean, and Chinese, the phoneme count was based on an algorithm designed to extract phoneme counts from Katakana, Hangul, and Pinyin. Japanese, Korean, and Chinese were treated differently to English, German, and French because Katakana, Hangul, and Pinyin scripts are reasonably phonetic. The accuracy of this initial analysis was then assessed by native speakers of each respective language and adjustments were made where appropriate. For English, German, and French, phoneme counts were based on a combination of an acoustic analysis, using audio samples from the animated television program, as well as graphemic and morphemic analyses. When phonemic identity was clear and unambiguous based on either a graphemic or a morphemic analysis, audio samples were not sought. For example, an audio sample was not sought in the case of the English Pokemon Blastoise because it is clear from both its spelling and its morphemes (blast + tor[toise]) that of the target phones, there is only a single occurrence of /b/. On the other hand, whether there is a /g/ in the name of the English Pokemon Yungoos is ambiguous. In instances like this, we sought audio samples from the animated television program to determine phonemic identity. On occasion, audio samples from the animated television program could not be sourced. This occurred twice in the English data set with the Pokemon named Regialeki and Regidrago, where it is unclear whether <g> represents the voiced velar plosive or the voiced postalveolar affricate. In these cases, we examined the linguistic behaviour of unofficial content creators whose content suggested that they were native Pokemon speakers. In the case of German, conversion from orthography to the phonological realization was implemented. This process implemented a set of rules, such as final devoicing of free morphemes, but it also encompassed some rules for the realization of <s> in German, as /s/, /z/, or /S/. However, because both the realization of <s> in cases of novel names and, more importantly, varying assimilation that influences voicing could not be relied upon, all names were checked by the second author who is a phonetician proficient in German. The manual control resulted in identifying problematic cases, especially involving the assimilation issues. For example, in Taubsi "Pidgeotto", <b> is devoiced as a result of regressive assimilation to /s/. There were some cases in which the automatic conversion recognized the segment as devoiced, even if it remained voiced, e.g., in Sengo "Zangoose", <g> pertains the voicing. In many cases, similarly to English, we relied on audio samples from the Pokemon community to seek for the most likely pronunciation. Since there is a lot of variation in German pronunciation, we sought multiple samples for the same name. This procedure allowed us to correct the automatic conversion in names such as Gelatini "Vanillite," Gelatroppo "Vanillish," and Gelatwino "Vanilluxe" regarding the initial <g> that is based on Italian pronunciation as an affricate [dZ], which is actually devoiced in German and realized as [tS]. In the case of French, it was difficult to find official recordings of many of the Pokemon names, so the services of a native French professional voice-over artist with considerable experience with the Pokemon franchise was engaged. A recording of the speaker was made, and the analysis was conducted by the third author, a non-native French speaking phonetician. This process was only done in the case of French because it was difficult to find official audio samples from which to analyse. In all languages except for Chinese and Korean, all target phones were counted. In Chinese (Duanmu, 2007, p. 24) and Korean (Sohn, 2019), there is no phonological opposition between voiced and voiceless plosives. Therefore, there is no data for/b/, /d/, and /g/ in these languages. Both languages do have phonological opposition between aspirated and unaspirated plosives, and on the advice of the volunteers who assessed the accuracy of the Chinese and Korean data, counts for aspirated and unaspirated /p/ were conducted separate to the initial /p/ count. Korean plosives are often voiced when they occur intervocalically (Sohn, 2019), and on the advice of the Korean volunteer, a count of intervocalic plosives was conducted. Aspirated and unaspirated /p/ in Chinese and Korean, and intervocalic /p/, /t/, and /k/ in Korean are not included in the cross-linguistic models and are analysed separately. Japanese and Korean have phonemically contrastive gemination on plosives; however, geminates were treated as single instances of the same sound because they have one place of articulation and one closure movement (i.e., they are simply long consonants, instead of consonants that involve double articulation). Since the analysis was conducted, two new Pokemon video games have been released which both include new canonical Pokemon; Pokemon Legends Arceus and Pokemon Scarlet/Violet (Generation 9 of the core series). These new Pokemon are not included in the present study. Therefore, the present study examines the names of 898 Pokemon spanning generations 1 through 8 (1996-2021) in six languages resulting in 5,388 tokens. In the following sections, we examine the relationship between voiced plosives, labial consonants, and base friendship. Unlike in previous Pokemonastic studies, Poisson regression is used to predict the occurrence of certain sounds based on base friendship, because while base friendship is represented numerically, it is not a continuous variable (Winter and Burkner, 2021). Table 1 reports the distribution of Pokemon per level of base friendship. Table 1 Distribution of Pokemon per level of base friendship. Base friendship Number of Pokemon 0 48 35 73 50 744 70 2 90 5 100 15 140 11 It is important to note that a certain amount of name borrowing occurs between languages. For example, the Pokemon known as Pikachu in English (base friendship = 50), is P'ik'ach'yu in Korean McCune-Reischauer romanization, Pikaqiu in Chinese Pinyin, and Pikachu in Japanese, German, and French. While Pikachu is a special case because it is a mascot for the franchise, the reader should be made aware that borrowing does occur between languages. As an illustration of borrowing across languages, Table 2 presents a list of the names of all starter Pokemon from the 8 generations of core games in their pre-evolution form. In the present study, no Pokemon names have been excluded from the analysis due to being borrowed from another language, because exclusion would need to be based on an arbitrary perception of similarity. This can be raised as a concern in a study that draws conclusions based on cross-linguistic patterns. However, there is enough cross-linguistic variability to suggest that when a name is borrowed from one language to another, it has been deemed appropriate for said language. Table 2 List of each pre-evolution starter Pokemon from all 8 generations of the core Pokemon video games. English Japanese Korean Chinese German French Bulbasaur Fushigidane Isanghaessi Miaowazhongzi Bisasam Bulbizarre Charmander Hitokage P'airi Xiaohuolong Glumanda Salameche Squirtle Zenigame Kkobugi Jienigui Schiggy Carapuce Chikorita Chikorita Ch'ik'orit'a Jucaoye Endivie Germignon Cyndaquil Hinoarashi Puk'ein Huoqiushu Feurigel Hericendre Totodile Waninoko Riak'o Xiaoju'e Karnimani Kaiminus Treecko Kimori Namujigi Mushougong Geckarbor Arcko Torchic Achamo Ach'amo Huozhiji Flemmli Poussifeu Mudkip Mizugoro Multchangi Shuiyueyu Hydropi Gobou Turtwig Naetoru Mobugi Caomiaogui Chelast Tortipouss Chimchar Hikozaru Pulkkotsungi Xiaohuoyanhou Panflam Ouisticram Piplup Potchama P'aengdori Bojiaman Plinfa Tiplouf Snivy Tsutaja Churibiyan Tengtengshe Serpifeu Vipelierre Tepig Pokabu Ttukkuri Nuannuanzhu Floink Gruikui Oshawott Mijumaru Sudaengi Shuishuita Ottaro Moustillon Chespin Harimaron Toch'imaron Halili Igamaro Marisson Fennekin Fokko P'uhokko Huohuli Fynx Feunnec Froakie Keromatsu Kaegumaru Guaguapaowa Froxy Grenousse Rowlet Mokuro Namolppaemi Mumuxiao Bauz Brindibou Litten Nyabi Nyaobul Huobanmiao Flamiau Flamiaou Popplio Ashimari Nurigong Qiuqiuhaishi Robball Otaquin Grookey Sarunori Hungnasung Qiaoyinhou Chimpep Ouistempo Scorbunny Hibani Yomboni Yantu'er Hopplo Flambino Sobble Messon Ulmogi Leiyanxi Memmeon Larmeleon Japanese names are written in Hepburn romanization, Korean names are written in McCune-Reischauer romanization, and Chinese names are written in Pinyin. 2.1. Statistical analysis All analyses were performed in R version 4.2.2 (R Core Team, 2013). For a full list of packages and versions, interested readers are referred to the annotated script in the following repository: The central hypothesis of the present study is that Pokemon names carry sound-symbolic information pertaining to the base friendship metric. In other words, when a listener hears a Pokemon name, they can make a better than chance assessment as to its friendship. To statistically test this hypothesis, we use a series of Poisson regression models with base friendship as the dependent variable and the sounds in their names as the predictor variables. Poisson regression models are a type of generalized linear model that are used to model non-continuous data. Since our dependent variable is not continuous, Poisson regression was deemed suitable for this task (for a clear exposition for this statistical analysis, see Winter (2019): Ch 13 as well as Winter and Burkner (2021)). As is shown in Table 1, the distribution of Pokemon per level of base friendship is highly skewed, with most Pokemon having a base friendship value of 50. We also explore the potential that base-friendship reflects size and combat ability, i.e., that bigger, stronger Pokemon are unfriendly, and that the patterns observed might model better to other metrics. To test this, we use a multivariate regression analysis examining the relationship between base friendship and combat and size attributes. Lastly, we use a series of multivariate Poisson regression analyses examining base friendship, size, and combat variables and the frequency of each phoneme to tease apart base friendship from these other metrics. 3. Results A descriptive analysis shows that there is a relationship between base friendship and the frequency of the six phonemes, whereby /p/ occurs most frequently in Pokemon with a base friendship of 140, while /g/ and /d/ occur most frequently in Pokemon with a base friendship of 0. Table 3 reports the average number of times that each phoneme occurs in each Pokemon name distributed by base friendship level. Table 3 Average number of times that each phoneme occurs in Pokemon names by base friendship level. Base friendship 0 35 50 70 90 100 140 /p/ 0.09 0.16 0.24 0.33 0.03 0.27 0.48 /b/ 0.06 0.15 0.19 0.25 0.15 0.18 0.07 /d/ 0.38 0.23 0.28 0.33 0.07 0.24 0.20 /m/ 0.21 0.26 0.20 0.25 0.30 0.08 0.09 /g/ 0.32 0.21 0.19 0.13 0.05 0.07 0.02 /w/ 0.03 0.04 0.06 NA NA 0.06 0.02 A generalized linear mixed-effects model was constructed with language included as a random variable to test the effect of phoneme frequency on base friendship (results reported in Table 4). These results show a significant effect for all phonemes other than /w/ (p < 0.001 in all cases) on base friendship where bilabial plosives (/p/ and /b/) are associated with high base friendship while /d/, /m/, and /g/ are associated with low base friendship. Table 4 Results of the generalized linear mixed-effects model applied to all samples testing the effect of phoneme count on base friendship. Preds. R 2 z-value p /p/ 0.044 15.74 <0.001 /b/ 0.006 4.78 <0.001 /d/ 0.009 -5.73 <0.001 /m/ 0.011 -7.55 <0.001 /g/ 0.05 -13.24 <0.001 /w/ 0 0.87 0.387 A second generalized linear mixed-effects model was constructed with language included as a random variable. This model was constructed to try to negate the influence of cross-linguistic borrowing that may exist in the previous model. To achieve this, any Pokemon whose phoneme count matched that of the same Pokemon in a different language was excluded from the analysis. For example, Pikachu, whose name consists of a single instance of /p/ in all languages, was only counted once in the dataset. This method also excluded Pokemon whose names were clearly not the result of borrowing. For example, the Pokemon known as zuruzukin zuruzukin in Japanese and scrafty in English are clearly not related. However, only one of these samples was included in the analysis because both names contain zero instances of all the examined phonemes, and therefore they have the same phoneme count. An alternate method for excluding names was considered whereby each name sextuplet would be manually examined and a judgement would be made as to whether there was evidence of borrowing. This method was deemed to be inappropriate given the arbitrary nature of the judgment call and for reasons addressed in the conclusion. In total, 2,124 samples were excluded from the previous model, resulting in 3,264 samples. The results of the second generalized linear mixed-effects model are presented in Table 5. The model revealed a significant effect for phonemes /p/, /d/, and /g/ of phoneme count on base friendship where /p/ is associated with high base friendship while /d/ and /g/ are associated with low base friendship. Table 5 Results of the second generalized linear mixed-effects model applied to all samples with unique phoneme counts. Preds. R 2 z-value p /p/ 0.017 7.53 < 0.001 /b/ 0.001 1.86 0.063 /d/ 0.002 -2.08 0.037 /m/ 0 -0.22 0.823 /g/ 0.015 -6.39 < 0.001 /w/ 0 -0.5 0.620 Following the cross-linguistic models, a series of generalized linear models were constructed to test the effects of phoneme count on base friendship in languages independently. This analysis was conducted on the entire dataset because it is not always clear which is the source language in borrowing. Those patterns observed in the generalized linear mixed-effects models generally held true when individual languages were examined. Bilabial plosives /p/ and /b/ were found to be significant predictors of high base friendship in all cases except for /b/ in French (see Table 6). The voiced non-bilabial plosives /d/ and /g/ were significant predictors of low base friendship in all cases other than the case of /d/ in English and French. Interestingly, the bilabial nasal /m/ was a significant predictor of low base friendship in all languages despite not achieving significance in the generalized linear mixed-effects model designed to limit the influence of name borrowing. /w/ was not found to be a significant predictor of base friendship in any language. Table 6 Z-scores for the regression analyses for the six phonemes across the six languages. English Korean Chinese Japanese German French /p/ 4.15*** 7.6*** 5.9*** 10.86*** 7.04*** 4.17*** /b/ 2.91** NA NA 1.65 4.83*** 0.56 /d/ -1.28 NA NA -4.57*** -4.77*** -1.08 /m/ -1.98* -4.35*** -2.67** -3.08** -4.28*** -2.09* /g/ -7.36*** NA NA -5.07*** -9.37*** -5.06*** /w/ -0.8 0.66 0.07 0.57 0.4 1.6 Asterisks reflect significance where *p < 0.05, **p < 0.01, and ***p < 0.001. These findings mirror those findings in earlier studies that have shown that voiced obstruents are related to increased referent size (e.g., Newman, 1933; Hamano, 1986) while bilabial consonants are related to cuteness in English and Japanese (Uno et al., 2020) and possibly other languages, so that what we are finding is possibly a relationship between size (or power) and sound rather than friendliness. To examine a potential relationship between base friendship, size (height and weight), and the sum of the combat aptitude parameters (attributes known as hit points, attack, defence, special attack, special defence, and speed), we conducted a multivariate regression analysis to explore a potential relationship between combat aptitude, size, and base friendship. As was observed in Kawahara et al. (2018), Pokemon height and weight measures are heavily right-skewed, so we took the natural logarithm of these measures. A significant regression equation was found (F(3,5,384) = 140.3, p < 0.001) with an R2 of 0.72. The results of this analysis are presented in Table 7. Table 7 Results of a multivariate regression analysis examining the relationship between base friendship and combat and size attributes. Metric t-value p Combat aptitude 7.23 <0.001 Log weight 9.58 <0.001 Log height 0.52 0.604 Combat aptitude and weight explain a significant proportion of variance in base friendship, where Pokemon with low base friendship are significantly heavier and stronger than those with high base friendship. We therefore conducted a series of multivariate Poisson regression analyses examining phoneme frequency as a predictor of base friendship, size, and combat aptitude. Given that /w/ was not found to be significant in any previous model, it was excluded from this analysis. These are reported in Table 8. The results show that base friendship has the strongest effect size with /p/ and /g/ frequency, but not of /b/, /d/, and /m/ frequency. Table 8 Results of a series of multivariate Poisson regression analyses examining base friendship, size, and combat variables and the frequency of each phoneme in all languages. Phone /p/ /b/ /d/ /m/ /g/ Preds. z-value p z-value p z-value p z-value p z-value p B. Friendship 5.42 < 0.001 1.59 0.112 -0.06 0.951 -4.32 < 0.001 -3.96 <0.001 Combat Total -2.58 0.010 -3.22 0.001 -0.63 0.529 2.43 0.015 0.96 0.337 Log Height 0.51 0.601 0.01 0.993 3.22 0.001 -5.44 < 0.001 -0.07 0.943 Log Weight -2.20 0.028 0.15 0.884 0.21 0.833 0.83 0.408 2.64 0.008 R2 = 0.25 R2 = 0.009 R2 = 0.012 R2 = 0.019 R2 = 0.024 B. Friendship refers to base friendship. 4. Discussion The current study contributes to the body of literature that examines the relationships between sounds and meanings in natural languages. It examines a corpus of over 5,000 Pokemon names from six languages and shows a systematic relationship between the Pokemon attribute known as base friendship and the phonemes that make up the names of Pokemon. Specifically, we hypothesized that labial consonants would occur more frequently in the names of high base friendship Pokemon while low base friendship Pokemon names would contain voiced obstruents. The findings show varying tendencies for labial phonemes. Bilabial plosives /b/ and /p/ are positively correlated with base friendship, as expected from the results of the previous studies. No effect for /w/ was found in our data. The bilabial nasal /m/, however, was negatively correlated with base friendship in our sample. The last one is a novel result in light of Kumagai (2020) and Kumagai and Kawahara (2017), who found a positive correlation between bilabial segments in general and infancy. In all languages with phonological opposition for voicing on plosives, /d/ and /g/ both showed a tendency to be associated with low base friendship, and this tendency was strongest with/g/ (z = -13.24, p < 0.001). This suggests that voiced plosives are reflective of increased threat, except in the case of /b/ which was generally associated with low base friendship. Since /b/ is both a voiced plosive and a bilabial consonant, no hypothesis was specified for this phoneme. Base friendship is arguably an abstract quality, which should have no physical representation. It has, however, been shown that seemingly abstract forms may evoke perceptual, affective, and sensory responses similar to real-world objects. In Lindauer's (1990) experiment, participants judged the shapes of takete and maluma, originally conceived by Kohler (1929, 1947), as being the least and the most friendly, respectively, as compared to neutral stimuli. In another experiment, Sidhu et al. (2021) examined how sound symbolism conveys abstract qualities. They investigated the perception of various personality traits in first names. The names were grouped into those that contained sonorants /m/, /n/, and /l/, and those that contained voiceless stops /p/, /t/, and /k/. The results suggest that sonorants and voiceless stops are associated with different personality factors, some of which may be linked to friendliness (Sidhu et al., 2019). Considering Ohala's (1994) frequency code, infancy is a signal for lack of threat, so it is difficult to explain the relationship between /m/ and low base friendship. Our analysis is the first one that disentangles the connotations of different labial segments and exposes this contradicting effect when considering base friendship rating in Pokemon. We initially hypothesised that the labial approximant, /w/, would be associated with high base-friendship because, like bilabial consonants, [w] appears to be a sound that infants acquire early in their development. Contrary to our expectation, however, /w/ was associated with neither high nor low base-friendship. Our admittedly post-hoc explanation is as follows. Kumagai and Kawahara (2022) propose that, in Japanese at least, infancy is represented by an abstract phonological feature [+labial] rather than the specific labial gestures of each consonant. In their experiment that explored sound symbolic relationships in the Japanese names of baby diapers, they showed that the voiceless bilabial fricative, /F/, carried the same sound-symbolic associations as other labial consonants, despite this fricative sound being acquired later in development (Ota, 2015). They thus argued that that the relationship between sound symbolic information and age of acquisition/usage frequency in infants is an abstract one, mediated by an abstract phonological feature. One potential explanation for why we observed no sound symbolic association with /w/ in the present study is that perhaps/w/ is not [+labial], or at least not fully [+labial],2 because phonetically speaking, /w/ involves both a labial gesture as well as a dorsal gesture; the International Phonetic Alphabet indeed considers [w] as labio-velar. Indeed, whether/w/ is specified as [+labial] or not is at best a contended issue, with /w/ sometimes phonologically behaving like a labial consonant but sometimes now (see, e.g., Nevins and Chitoran, 2008). In short, phonetically speaking, /w/ is not unambiguously labial, as it also involves a narrowing gesture at velar, and perhaps relatedly, /w/ is not unambiguously phonologically [+labial] either. This ambiguous status of /w/ may lie behind the current results. In the current study we report findings that friendliness may also have a physical representation, as friendly Pokemon tend to be smaller and weaker than their unfriendly counterparts. An attentive reader may nevertheless ask whether the current study tests friendliness explicitly, or whether our results are simply reflecting known size effects in sound symbolism (Newman, 1933; Hamano, 1986; Kawahara and Shinohara, 2012). The Poisson multivariate analysis that was conducted to test this possibility did show that the base friendship model had a stronger effect size than combat, weight, and height models for/p/ and /g/ frequency, but not for other phonemes. Voiced obstruents have been shown to be predictors of size in other Pokemonastic studies (Kawahara et al., 2018). Although it was not found to be a significant predictor in Japanese, Korean, and French, high /b/ frequency trended toward high friendliness in all languages, suggesting that friendliness and size are expressed differently sound symbolically. The relationship between the frequency of the bilabial nasal /m/ and base friendship presents another piece of evidence that base friendship is not simply a reflection of size. /m/ frequency was shown to be a significant predictor of base friendship in all languages, whereby Pokemon with low base friendship generally had a greater occurrence of /m/ in their names. This is a surprising finding given that bilabial consonants (in English and Japanese at least) appear to be associated with cuteness and infancy (Kumagai, 2020). However, it is important to note here that /m/ was not found to be significant in the second generalized linear mixed-effects model which was designed to limit the effects of name borrowing between languages. Therefore, this relationship may be limited to Japanese, or English given that these languages are the most likely candidates as the source for borrowing. Interestingly, /m/ frequency was not a significant predictor of weight, but high /m/ frequency was shown to connote shortness (although this was only shown to be significant in Japanese). Given the negative relationship between base friendship and /m/ frequency, if base friendship is simply a reflection of Pokemon size, then a positive relationship between height and /m/ frequency would be expected. This was clearly not the case. It is interesting to examine our findings through the lens of the hypothesis promulgated by Shih et al. (2018) that elements of sound symbolism possibly reflect the survivability of Pokemon. Here however, we divert from their assumption that symbolism in human languages communicates the qualities of one's allies and tentatively put forth our own hypothesis that relates more closely to alarm call theory (Adelman et al., 2018). Pokemon are both allies and enemies in the Pokemon world. In the non-Pokemon world, many non-human primates have elaborate alarm calls that communicate information regarding approaching predators. East African vervet monkeys, for instance, have an alarm call system that differentiates between mammalian, avian, and snake shaped predators (Seyfarth et al., 1980). It is possible, therefore, that elements of sound symbolism in human languages are the result of an alarm call system which early humans used to warn others of approaching danger, as hypothesised by Adelman et al. (2018). In the context of the findings of the present study, perhaps patterns relating to base friendship are the result of an alarm call system that communicated the potential threat of an observed predator. This may explain the apparent sound symbolic relationship between demeanour and size because larger predators would be more likely to engage early humans as prey. This also may give insight into why the relationship between voiced obstruent frequency and weight appears to have a greater effect size than height in Pokemonastic studies (Kawahara et al., 2018; Shih et al., 2018). In professional combat sports, fighters are separated into weight classes--rather than height classes--because weight is a better predictor of threat. We find this proposition of a sound symbolic pattern that reflects threat more convincing than one that expresses the survivability of one's allies because of convergent evolution--that under the same environmental pressures, separate species will exhibit similar traits--and the prevalence of alarm call systems in the animal kingdom. That said, we note that the present study does not constitute sufficient evidence to substantiate this hypothesis but discuss it here with the hope that further investigation may yield interesting results. Ideally, this study would have been conducted on a phonetic analysis, rather than using a count of the target phones. A phonetic analysis would open interesting areas of enquiry into whether sound symbolism is phonetically or phonemically based. Additionally, a phonetic analysis may also provide a more accurate and robust method for excluding borrowed samples. Borrowing can be problematic in a cross-linguistic study because relationships between sounds and meanings that appear to be occurring across languages when they simply occur in the source language. In practice, however, excluding borrowed names in an objective fashion is difficult because it is not always clear when a name is borrowed and when it comes from a similar source. For example, the Pokemon known as Omanyte in English resembles a species of extinct marine molluscs known as ammonites. Omanyte is known as Omunaito in Japanese, Amnait'u in Korean, Amonitas in German, and Amonita in French. Given that these names are clearly based on the Latin name for ammonite, it is difficult to ascertain whether these are true borrowings, or whether they are based on the same source. As is shown in Table 2, there is considerable variation between languages in the names of the pre-evolution starter Pokemon. Therefore, we may reasonably determine that even when borrowing does occur, it has been ascertained that the borrowed name--and its sound/meaning associations--is appropriate to the adoptive language. Finally, an anonymous reviewer noted that those individuals that select the names for Pokemon might also be acquainted with the principles of sound symbolism and therefore might take into consideration these principles in the naming process. Although friendship has not existed in all generations of the video games, this is indeed a possibility, and one that we must consider given that there is little literature on how Pokemon are named. However, this concern does not trivialize our results, we believe, since what we are exploring is ultimately the knowledge of sound symbolism that human beings have. We are unveiling some aspects of such knowledge through the lens of Pokemon names. If the Pokemon designers applied some sound symbolic principles that they have, that is most likely because they wanted to convey the sound symbolic meanings to the customers. What we found, we believe, is thus shared knowledge about how meanings can be expressed in terms of sounds. 5. Conclusion The present study shows a systematic cross-linguistic relationship between frequency of phones and the Pokemon attribute known as base friendship. It shows that /p/ represents high friendliness in all the examined languages, while /g/ is shown to represent unfriendliness in all languages. This is an important finding because friendliness is arguably an abstract quality and can therefore not be explained by a natural relationship between the shape of an object and the shape that the oral cavity conforms to when making the sounds that describe or name said object. The finding that sound symbolic patterns pertaining to friendliness hold cross-linguistically suggests that more is at play in sound symbolism than a natural relationship between shape and sound. Data availability statement Publicly available datasets were analyzed in this study. This data can be found here: Author contributions AK: devised and supervised the experiment, conducted the phoneme count for English, created the algorithms for counting phonemes in Chinese, Japanese, and Korean, conducted the statistical analysis, created the first draft of the paper, and editing. AC: conducted the phoneme count for German, created the second draft of the paper, and editing. EL: conducted the phoneme count for French and editing. SK: conducted the statistical analysis and editing. All authors contributed to the article and approved the submitted version. Funding This study was supported by Japan Society for the Promotion of Science (Tokyo, JP) grant number: 20K13055. This grant was also used to pay a voice over artist who recorded the French Tokens. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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PMC10000298 | Front Cell Neurosci Front Cell Neurosci Front. Cell. Neurosci. Frontiers in Cellular Neuroscience 1662-5102 Frontiers Media S.A. 10.3389/fncel.2023.1114037 Neuroscience Original Research Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism Tian Tian 1 + Cai You 1 2 + Qin Xin 3 Wang Jiangang 4 Wang Yali 4 Yang Xin 1 * 1Shenzhen Key Laboratory of Translational Research for Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China 2Department of Neurology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China 3Department of Medicine, Djavad Mowafaghian Centre for Brain Health, The University of British Columbia, Vancouver, BC, Canada 4Henan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, China Edited by: Leandro M. Alonso, Brandeis University, United States Reviewed by: Marco Fuenzalida, Universidad de Valparaiso, Chile; Xiong Wang, Huazhong University of Science and Technology, China; Xiaoguang Li, Huazhong University of Science and Technology, China *Correspondence: Xin Yang, [email protected] +These authors have contributed equally to this work This article was submitted to Cellular Neurophysiology, a section of the journal Frontiers in Cellular Neuroscience 24 2 2023 2023 17 111403702 12 2022 31 1 2023 Copyright (c) 2023 Tian, Cai, Qin, Wang, Wang and Yang. 2023 Tian, Cai, Qin, Wang, Wang and Yang This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction Forebrain neural networks are vital for cognitive functioning, and their excitatory-inhibitory (E-I) balance is governed by neural homeostasis. However, the homeostatic control strategies and transcriptomic mechanisms that maintain forebrain E-I balance and optimal cognition remain unclear. Methods We used patch-clamp and RNA sequencing to investigate the patterns of neural network homeostasis with suppressing forebrain excitatory neural activity and spatial training. Results We found that inhibitory transmission and receptor transcription were reduced in tamoxifen-inducible Kir2.1 conditional knock-in mice. In contrast, spatial training increased inhibitory synaptic connections and the transcription of inhibitory receptors. Discussion Our study provides significant evidence that inhibitory systems play a critical role in the homeostatic control of the E-I balance in the forebrain during cognitive training and E-I rebalance, and we have provided insights into multiple gene candidates for cognition-related homeostasis in the forebrain. homeostasis GABA forebrain cognition E-I balance significance statement This study was supported by Shenzhen Science and Technology Program (Grant Nos. KQTD20210811090117032 and JCYJ20220530154409022); NSFC-Guangdong Joint Fund-U20A6005 (Grant No. ZDSYS20200828154800001); and Science and Technology Planning Project of Henan Province (212102310824). pmcIntroduction Cognitive health is essential for human and animal survival. Cognitive dysfunction is a core symptom in many neurological disorders, including Alzheimer's disease (AD) (Yang et al., 2018) and schizophrenia (SZ) (Bhat et al., 2021). Excitation-inhibition (E-I) balance in the hippocampus and cerebral cortex is essential for normal cognition (Vogels et al., 2011; Yu et al., 2014; Barron et al., 2016). A functional balance between excitatory and inhibitory synapses (E-I balance) is established and maintained throughout life (Turrigiano and Nelson, 2004). Among them, excitatory synaptic transmission is driven mainly by glutamatergic synapses, whereas inhibitory synaptic transmission involves GABAergic and glycinergic signaling. A major function of homeostasis is to regulate neuronal activity in a negative feedback manner, thus playing an important role in maintaining forebrain E-I balance (Gilbert et al., 2016) and neuronal activity at the appropriate cognitive level in the ever-changing world (Huber, 2018). At the individual synaptic level, the E-I ratio of neural inputs can be locally regulated by plasticity (Eichler and Meier, 2008). At the neuronal level, E-I balance is globally controlled via an excitable threshold and is homeostatically regulated by glutamatergic and GABAergic transmission (Cagetti et al., 2004; Eichler and Meier, 2008). Furthermore, experience or the environment shapes the forebrain E-I balance through homeostatic regulation (Bateup et al., 2013; Herstel and Wierenga, 2021). For example, brief (2-3 days) deprivation of the vision of one eye in rodents (monocular deprivation) reduces network activity (Miska et al., 2018) and improves the acuity of the non-deprived pathway (Fischer et al., 2007). However, the responses of forebrain E-I balance and transcriptome to cognitive experience are not well understood. Inwardly rectified potassium channel 2.1 (Kir2.1) was wide used to study synaptic and neuronal homeostatic compensative mechanism. Overexpression of Kir2.1 causes hyperpolarization to inhibit neural excitation (Okada and Matsuda, 2008) and network balance control (Paradis et al., 2001). Adult-onset expression of Kir2.1 could induce homeostatic plasticity and presynaptic transcriptional changes in the fruit fly brain (Harrell et al., 2021). Silencing pyramidal neurons with Kir2.1, after synapse formation, causes a homeostatic increase in synaptic inputs to stabilizes network activity (Burrone et al., 2002; Turrigiano, 2011). However, homeostatic regulation of E-I balance in the hippocampus when Kir2.1 is specifically overexpressed in forebrain excitatory neurons remains unknown. Furthermore, the pattern of this rebalance of neural activity in response to subsequent spatial training or environmental changes remains unclear. Here, we assessed the homeostatic regulation of E-I balance in the forebrain at the electrophysiological and transcriptomic levels by spatial training and overexpressing of Kir2.1 in forebrain excitatory neurons. We also indicated that inhibitory transmission and inhibitory transcriptome mechanisms are important for the homeostatic control of forebrain E-I balance and cognitive experience. This study may provide a reference for understanding the homeostatic control of specific types of neuronal activity abnormalities in diseases including AD and SZ and also suggests a number of potential candidate genes related to neural homeostasis control and cognition. Materials and methods Animals All animal experiments were performed according to the protocol approved by the Institutional Animal Care and Use Committee of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences. Adult (90 +- 2 days old) male C57BL/6 mice were used in this study. Generation of the Kir2.1 mutant mice The Rosa-CAG-Flag-Kir2.1-2A-tdTomato-WPRE targeting vector was designed with a CMV-IE enhancer/chicken-actin/rabbit b-globin hybrid promoter (CAG), FRT site, loxp-flanked STOP cassette (with stop codons in all three reading frames and a triple poly(A) signal), Flag-Kir2.1-2A-tdTomato sequence, woodchuck hepatitis virus post-transcriptional regulatory element (WPRE, to enhance mRNA transcript stability), a poly(A) signal, and attB/attP-flanked PGK-FRT-Neo-poly-A cassette. The entire construct was inserted between exons 1 and 2 of the Gt (ROSA)26Sor locus via electroporation into C57BL/6-derived embryonic stem (ES) cells. Targeted ES cells were selected and injected into C57BL/6 blastocysts, and chimeric animals were bred into C57BL/6 mice to generate Kir2.1loxp/loxp mutant mice. The conditional mutant strain of theKir2.1 mice was developed by crossing Kir2.1loxp/loxp mice with Tg (CaMK2a-Cre/ERT2) mice (Stock number: 012362, Jackson Laboratory, Bar Harbor, Maine, USA). Male adult (90 +- 2 days old of age) Kir2.1 (+) mice and their Kir2.1 (-) littermates were treated with tamoxifen (Tam) dissolved in core oil (100 mg/kg, i.p., once per day for 5 consecutive days). After recovery for 2 days, the animals were used for the following experiments. FIGURE 1 Inhibition of forebrain excitatory neural activity in Kir2.1 knock-in mice. (A) A strategy for inducible expression of the Kir2.1 channel (Tg1) in the forebrain neurons by crossing a Tg1 line with a Cre/ERT2 transgenic line under control of CaMKIIa promoter (Tg2), and representative fluorescence images of Kir2.1-tdTomato protein in a sagittal section from the Kir2.1 (+) mice. Bar = 0.5 mm (B). The Kir2.1 currents are plotted against the holding potentials in CA1 pyramidal neurons from the Kir2.1 (+) and the Kir2.1 (-) mice. Traces above the plot are the example recordings from the individual mice. Data are mean +- SEM (n = 16 recordings/8 mice per group, ANOVA*p < 0.01). (C) The CA1 pyramidal neurons in the Kir2.1 (+) mice require more currents to elicit firing with a 2 ms current step. Top, examples of sub-threshold membrane depolarization and the first action potential elicited by current injection. Square pulses illustrate increasing current injection. Bottom, a bar graph shows the threshold currents required for action potential firing in CA1 pyramidal neurons from the Kir2.1 (+) and the Kir2.1 (-) mice. Data are mean +- SEM (n = 12 recordings/6 mice per group, ANOVA *p < 0.01). (D) Firing frequency is reduced in the Kir2.1 (+) mice. Top, examples of the CA1 pyramidal neuron firing trains in response to current injection. Bottom, firing frequency is plotted against current injection (500 ms duration, 0 to 500 pA, 50 pA steps). Data are mean +- SEM (n = 12 recordings/6 mice per group, ANOVA*p < 0.01). (E) Morphological features of a recorded CA1 pyramidal neuron filled with 50 mM Fluo-5F. Box indicates a dendritic segment used for Ca2+ image. Ca2+ transient in the dendrite was induced by glutamate uncaging. Each image is an average of 6-8 frames taken 1 s before and 5 s after glutamate uncaging (0 s), as indicated. (F) Reduction in the peak amplitudes of the dendritic spine Ca2+ transients in the Kir2.1 (+) mice. Representatives are the individual traces (gray lines) and averaged responses (black and red lines) recorded in the Kir2.1 (-) mice and Kir2.1 (+) mice. Time courses of fluorescence changes and the NMDA receptor-mediated currents induced by glutamate uncaging recorded in the slices from the Kir2.1 (+) and the Kir2.1 (-) mice. Data are mean +- SEM (n = 12 recordings/6 mice per group, ANOVA*p < 0.01). Bar: 200% and 50 pA. In this Figure, the experiments were performed in the Kir2.1 (+) and the Kir2.1 (-) mice 2 days after 5 consecutive days of vehicle or tamoxifen administration. Morris water maze and open field The water maze task was performed with a circular tank (120 cm diameter) filled with opaque water (21-23degC) and a hidden platform (6 cm diameter) submerged 1 cm below the surface of the water. The devices (tank and platform) and software [WMT-100] were purchased from Tai Meng Technology Co., Ltd. (Chengdu, China). Before the start of the training trials, the mice were allowed to acclimate to the testing room for 30 min. Mice were trained to find the invisible platform within 70 s on six consecutive days, with four trials per day. If a mouse failed to find the platform within 70 s, it was guided to find the platform and allowed to remain there for 15 s. Escape latency to find the hidden platform, path length, and swim velocity were recorded. After 2 days of rest, the platform was removed, and the mouse was allowed to search for the pool for 70 s (probe tests). The time spent in each quadrant was analyzed. No training means no learning and probe process in MWM, but the animals still swim in the water, while training means an intact MWM experiment. And mice sacrificed at day 6 after probe test. Locomotion activity was measured in clear boxes measuring 42 cm x 42 cm, outfitted with photo-beam detectors for monitoring horizontal and vertical activity. Data were collected via a PC. Mice were placed in a corner of the open-field apparatus and left to move freely. Mice were not exposed to the chamber before testing. Data were individually recorded for each animal during 30 min. Electrophysiological recordings in vitro As described previously (Gilbert et al., 2016; Yang et al., 2018), slices (350 mm) of the hippocampus were obtained from male mice at 90 days of age and were placed in a holding chamber for at least 1 h, and saturated with 95 and 5% CO2. Artificial cerebrospinal fluid (ACSF, in mM): 124 NaCl, 3 KCl, 1.25 NaH2PO4, 2 MgCl2, 2 CaCl2, 26 NaHCO3, and 10 glucose. The internal solution contained (in mM): 140 potassium gluconate, 10 HEPES, 0.2 EGTA, 2 NaCl, 2 MgATP, and 0.3 NaGTP, 5 QX-314was used for sEPSCs or mEPSCs, and 140 CsCl, 10 HEPES, 0.2 EGTA, 2 NaCl, 2 MgATP, and 0.3 NaGTP, 5 QX-314 was used for sIPSCs or mIPSCs. The temperature for the patch clamp recording is maintained at about 30 degrees, the electrode enters the liquid surface and corrects the liquid junction potential, and the cell with a resistance less than 20 MO after breaking through the cell membrane is considered to be usable. The current-voltage relations for transfected and control neurons were calculated by recording whole-cell currents under a voltage clamp. Voltage steps in 10 mV increments were applied every 250 ms. To measure the amount of current required to reach the action potential threshold, a series of current steps (2 ms or 500 ms duration, 0-1,000 pA range with 100 pA step increments) were injected into the cell until an action potential was generated. Under voltage clamp, the patched cell was held at -70 mV. A bipolar stimulating electrode (FHC Inc., Bowdoin, ME, USA) was placed in the Schaffer collaterals to deliver the stimuli, and the evoked excitatory postsynaptic currents (EPSCs) or inhibitory postsynaptic currents (IPSCs) were recorded under 30 mM bicuculline (Tocris Bioscience, Bristol, UK) or 10 mM CNQX (Tocris Bioscience, Bristol, UK), respectively. Without TTX (Tocris Bioscience, Bristol, UK), spontaneous EPSCs or spontaneous IPSCs were recorded with an external solution containing 30 mM bicuculline or 10 mM CNQX (Tocris Bioscience, Bristol, UK). Miniature EPSCs or miniature IPSCs were recorded with an external solution containing 1 mM TTX, 30 mM bicuculline (Tocris Bioscience, Bristol, UK), or 10 mM CNQX (Tocris Bioscience, Bristol, UK). The synaptic currents were monitored using an Axon 200 B amplifier (Molecular Devices). Spontaneous events were handpicked and analyzed using the Clampfit 10.2 software (Molecular Devices, Sunnyvale, CA, USA), using template matching and a threshold of 5 pA. All data were acquired at 10 kHz and filtered using a low-pass filter at 2 kHz. Ca2+ imaging Uncaging of MNI-glutamate, calcium imaging, and whole-cell recordings were performed under a DIC/fluorescence Olympus microscope (FV1000-BX61WI). Slices with a thickness of 300 mm were prepared as described above. The slices were kept at room temperature for at least 1.5 h before being transferred to the recording chamber. Twenty ml of oxygenated magnesium-free ACSF containing 0.2 mM caged glutamate (Tocris Bioscience, Bristol, UK), 1 mM TTX, 30 mM bicuculline, and 10 mM CNQX at 30degC was perfused into the slice recording chamber through a custom-designed flow system driven by pressurized 95% O2-5% CO2 at roughly 2 ml/min. Slices were examined under a 20 x objective for proper targeting of tdTomato-expressed CA1 pyramidal neurons. To target whole-cell recordings, cells were visualized at a high magnification (60 x objective, 1.0 NA; LUMPLFLN60XW, Olympus). Kir2.1-positive neurons, which were selected on the basis of their pyramidal somata detected under DIC, were RFP-positive on the monitor. Patch pipettes (3-5 MO resistance) made of borosilicate glass were filled with an internal solution containing (in mM): 140 potassium gluconate, 10 HEPES, 2 NaCl, 2 MgATP, and 0.3 aGTP, with 20 mM Alexa594 and 50 mM Fluo-5F. For calcium imaging, the neurons were filled via the patch electrode for 10-20 min before imaging. The dendrites of the recorded neurons were 30-60 mm below the surface of the slice. Laser scanning and photo stimulation were performed using a 60 x objective lens. One laser was tuned to 405 nm (FV5-LD405-2) to activate MNI-glutamate. The second was tuned to 800 nm (Ti: sapphire laser; 100 fs pulses; Mai Tai HP DeepSee, Spectra-Physics) for the excitation of Alexa Fluor-594 and Fluo-5F. Calcium signals were used to locate dendritic spines 30-80 mm from the soma. The selected dendrite was scanned repeatedly with a series of 200 scans (scan dimensions: 30 mm x 30 mm, 5 mm x 5 mm; 100 ms per scan). The uncaging laser spot was located ~1 mm away from the spine in Figure 1E. In the first scan, acquisition of NMDAR currents (Axon200B and FV10-ANALOG in our BX61WI microscope) and calcium signals began, and in the 10th frame, uncaging occurred with a constant area 0.25 mm2. Glutamate was uncaged using 5-30 ms pulses to generate the I-O curve of the laser strength calcium-NMDAR current under voltage clamp (Vh = -70 mV). To ensure that uncaging was performed in a constant location, image drift was corrected before each line scan acquisition by collecting a frame scan and calculating the cross-correlation to a reference image region of interest (ROI) analysis from these scans, as explained below. Fluorescence changes were analyzed off-line with laboratory-written software using the IGOR-Pro programming environment (Wavemetrics). To study the time course and amplitude of Ca2+ rise, the average fluorescence was measured in small "ROIs" (2.25-4 mm2) and converted to the percentage change in fluorescence: DFFo=100x(F-Fr)/(Fr-B), where F is the measured fluorescence signal at any given time, Fr is the average fluorescence from the scans preceding the stimuli, and B is the average value of the background fluorescence in the scanned field that does not contain any part of the dye-filled cell. RNA-sequencing and data analysis Total RNA from the hippocampus and cortex was purified using the RNeasy Plus Micro Kit (Qiagen, Hilden, Germany). RNA quality (RIN 8-9) and quantity were analyzed on a 2,100 Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA) using RNA 6,000 Pico chips; ds-cDNA was produced using the Ovation RNA-seq system V2 (NuGEN, San Carlos, CA, USA) and fragmented using a Covaris S-Series System (Covaris, Woburn, MA, USA). DNA fragments in the 150-300 bp size range were recovered to construct a sequencing library using the Encore NGS Library System I (NuGEN, San Carlos, CA, USA) for 100 bp paired-end RNA-seq using the Illumina HiSeq-2500 sequencer. Raw data were processed using the cutadapt (Martin, 2011) software to remove joints and filter low-quality reads, and 77-121 M clean reads were obtained for each sample with an average Q30 > 95%. RNA-sequencing data alignment and differential gene expression analysis were performed using Tophat2 (Kim et al., 2013) and edgeR (Robinson et al., 2010). Specifically, RNA-sequencing data were aligned to the reference genome (mm10 NCBI buid 38.1) using Tophat2, using default parameters. Uniquely mapped and properly paired alignments were used for further analyses. FeatureCounts (Liao et al., 2013) were used to count the number of reads mapped to each gene. Prior to differential gene expression analysis, for each sequenced library, the read counts were adjusted using the edgeR program package through one scaling normalized factor. Differential expression analysis under the two conditions was performed using the edgeR R package with bcv = 0.1. P-values were adjusted using the Benjamini and Hochberg method. A corrected P-value of 0.05 and absolute fold change of 2 were set as the thresholds for significantly differential expression. Sample cluster analysis of all detected genes was performed using the pheatmap R package.1 Gene Ontology (GO) enrichment analysis of differentially expressed genes was performed using the clusterProfiler R package (Yu et al., 2012; Wu et al., 2021), in which the gene length bias was corrected. Fluorescence imaging As described previously (Shi et al., 2021; Tian et al., 2021), brain tissue was perfused and fixed with 4% paraformaldehyde (PFA) solution, dehydrated with 30% sucrose, and frozen to obtain 30 mm sagittal sections with a cryostat microtome (Leica CM1950). Fluorescence images were obtained using a FV1000-BX61WI microscope. Statistical analysis Statistical analysis of the transcriptomics can be found in the RNA-sequencing and data analysis sections. Other statistical analyses were performed using Graphpad Prism version 8. The amount of data collected is described in the corresponding figure legend. The statistical variables in Figures 1-3 are all continuous variables, described using mean and standard deviation, represented as mean +- SEM. In Figures 1, 2, one way ANOVA were used to compare the differences between the Tam (+) group and the other three groups. In Figures 3A, B, an independent samples t-test was used to compare the differences between the Kir2.1 (+) and Kir2.1 (-) groups. One-way analysis of variance (ANOVA) was used in Figures 3C, D, and the Bonferroni correction was used for multiple comparisons between different groups. The description of the significance levels of p-values is also given in the corresponding figure legends. FIGURE 2 GABA transmission reduction play an important role in E-I rebalance in CA1. (A,B) Whole-cell patch clamp recordings from CA1 pyramidal neurons in the slices from the Kir2.1 (-) and the Kir2.1 (+) mice. Representatives and bar graph of the spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs). Data are mean +- SEM (n = 12 recordings/6 mice per group, ANOVA*p < 0.01). (C,D) Whole-cell patch clamp recordings from CA1 pyramidal neurons in the slices from the Kir2.1 (-) and the Kir2.1 (+) mice. Representatives and bar graph of the miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs). Data are mean +- SEM (n = 12 recordings/6 mice per group, ANOVA*p < 0.01). (E) The stimulus intensities are plotted against the evoked EPSC and IPSC recorded in the CA1 area of the hippocampus from the Kir2.1 (-) and the Kir2.1 (+) mice. Data are mean +- SEM (n = 10 recordings/5 mice per group), and the excitatory divide inhibitory ratio remained comparable between each groups. FIGURE 3 Homeostatic modulation of forebrain E-I balance via GABA transmission related to cognitive level and experience. (A) The Kir2.1 (+) mice show abnormal performance in a hidden platform version of the Morris water maze. The latency to reach a hidden platform is plotted against the blocks of trials. N = 8 mice per group, t-test, *p < 0.05 and **p < 0.01. (B) The percentage of time spent in search of a hidden platform in the target quadrant during the probe trial, t-test, *p < 0.01. (C,D) Whole-cell patch clamp recordings from CA1 pyramidal neurons in the slices from the Kir2.1 (-) and the Kir2.1 (+) mice. Representatives and bar graph of the miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs). Data are mean +- SEM, (n = 10 recordings/4 mice per group, ANOVA, *p < 0.05 and **p < 0.01). Results Inhibition of forebrain excitatory neural activity in Kir2.1 knock-in mice To study the homeostatic regulation of E-I balance in the forebrain, we genetically suppressed forebrain excitatory neural activity by conditional expression of the inward rectifying potassium channel. Targeting strategies and corresponding genotypic assays are described in detail in the (Section "Materials and Methods). Adult mice received 5 days of tamoxifen (Tam) or vehicle (Veh) treatment, showing successful expression of Kir2.1 channels by morphological and functional confirmation . First, we showed the presence of a tdTomato-tagged Kir2.1 protein in the forebrain excitatory neurons . Second, The Kir2.1 currents were plotted against the holding potentials in CA1 pyramidal neurons from Kir2.1 (+) and Kir2.1 (-) mice. The (+)/Tam group mice exhibited large inward rectifying potassium currents (green) recorded from a 250 ms voltage clamp from -160 to -10 mV with Kir2.1 overexpression compared to other groups . Third, the (+)/Tam group mice had an increased threshold for action potential firing with a 2 ms current step injection compared to the other groups . The CA1 pyramidal neurons in the Kir2.1 (+) mice required more currents to elicit firing with a 2 ms current step and less firing probabilities in vitro with 500 ms current step injection in the (+)/Tam group mice than in others . Finally, the (+)/Tam group mice showed less calcium influx in Kir2.1 (+) neurons compared to others with MNI-glutamate uncaging (>10 ms) under a two-photon microscope. Together, these data demonstrate that excitatory neural activity in the forebrain is selectively inhibited by Kir2.1 overexpression. GABA transmission reduction play an important role in E-I rebalance in CA1 To study the changes in E-I homeostatic balance after inhibition of forebrain excitatory neural activity, we evaluated the changes in spontaneous and miniature neural transmission in the hippocampus, which is one of the most important areas of the brain for spatial cognition. We observed a reduction in spontaneous EPSCs, but not spontaneous IPSCs in the hippocampal principal neurons . However, the frequency of both miniature mEPSCs and mIPSCs decreased after Kir2.1 overexpression in forebrain pyramidal neurons, and the amplitude of mIPSCs decreased after Kir2.1 overexpression in the forebrain . Furthermore, both evoked IPSCs and evoked EPSCs were reduced after Kir2.1 overexpression in the forebrain of Kir2.1 (+)/Tam group mice compared to those of the other groups, but the E-I currents remained balanced . These data indicate that reduction in GABA transmission plays an important role in compensating for the E-I imbalance in CA1 elicited by pyramidal neural inhibition. Homeostatic modulation of forebrain E-I balance via GABA transmission related to cognitive level and experience In an ever-changing world, experiences regulate E-I homeostatic balance, and rebalanced E-I networks are often thought to optimize learning and memory (Mizumori and Jo, 2013; Huber, 2018; Girardeau and Lopes-dos-Santos, 2021). To study the association between E-I homeostatic balance and cognition, we evaluated the cognitive level in Kir2.1 (+) mice and tested the changes in miniature postsynaptic currents in the hippocampus with or without spatial training. As many of the previous tests showed no differences in neuronal activity-related parameters among the negative control groups, we only examined the parameter changes between Kir2.1 mice with (Kir2.1 (+)) or without tamoxifen (Kir2.1 (-)) induction treatment in the follow-up experiments. First, we showed that compared with Kir2.1 (-) mice, Kir2.1 (+) mice spent more time reaching the escape platform during the 5-day training session and less time in the target quadrant during probe testing , indicating learning and memory impairments in Kir2.1 (+) mice, while no obvious difference in swimming speed in MWM and travel distance in the open field was found between Kir2.1 (-) and Kir2.1 (+) mice . Next, we scarified them and compared the miniature postsynaptic currents in trained mice or untrained Kir2.1 (+) and Kir2.1 (-) animals. We found that both excitatory and inhibitory transmission increased after 5-day spatial training in the control group Kir2.1 (-) mice . However, only GABA transmission, that is, the amplitude of hippocampal mIPSCs, was enhanced after the 5-day spatial training in Kir2.1 (+) mice . These data indicate that homeostatic modulation of forebrain E-I balance via GABA transmission may be related to cognitive level and experience. The inhibitory receptor transcriptome plays an important role in homeostatic control of E-I balance and cognitive experience The changes of mIPSC amplitude could be correlated to reduction in inhibitory/GABA receptors in response to cognitive experiences and E-I balance, we determined the underlying genome-wide transcriptome difference in the cortex and hippocampus of trained or untrained Kir2.1 (+)/Kir2.1 (-) mice via RNA sequencing. Details of sample grouping and naming, as well as sequencing data, can be found in Figure 4A and Supplementary Table 1; 77-121 M clean reads were obtained for each sample, with an average Q30 > 95%. The count expression matrix for all samples is shown in Supplementary Table 2. Unsupervised clustering of all gene expression profiles between samples showed that spatial training induced more severe transcriptome perturbation in the hippocampus than the overexpression of Kir2.1 in the cortex . This indicates that spatial training has a more direct effect on the hippocampus, while Kir2.1 overexpression has a more direct effect on the cortex. A detailed list of differentially expressed genes (DEGs) in each group is shown in Supplementary Table 3. From the results of the GO analysis of DEGs caused by Kir2.1 overexpression, we found that the Kcnj2 gene (Kcnj2 is the gene symbol name of Kir2.1) was significantly upregulated, this was expected given the fact that they are overexpressing Kir. Hence it served as a control. However, GABA and glycine receptors were significantly downregulated in both the cortex and hippocampus . However, in the spatial training group, GABA and glycine receptors were significantly upregulated in both the cortex and hippocampus , particularly in the Kir2.1 (+) group . This indicates that the transcription mechanism for inhibitory transmission or chloride homeostasis is an important strategy for homeostatic control of the E-I balance in the forebrain network and also suggests many gene candidates for cognition-related homeostasis in the forebrain. FIGURE 4 Inhibitory receptor transcriptome plays an important role in homeostatic control of E-I balance and cognitive experience. (A) Grouping and naming information for RNA-Seq samples. (B) Unsupervised clustering of all gene expression profiles between samples; the distance of the top tree indicates the difference between samples, with the further the distance, the greater the difference. (C) Gene ontology analysis of differentially expressed genes in the Kir2.1 (+) mice. (D,E) Gene ontology analysis of differentially expressed genes in the spatial training groups. (C-E) X axis is sorted by the log2 (Fold Change), red represents upregulated, blue represents downregulated, and white is shown around 0. "1" = ion channel complex (GO: 0034702), "2" = inhibitory synapse (GO: 0060077), "3" = GABA-A receptor complex (GO: 1902711), "4" = glycinergic synapse (GO:0098690). Discussion In the present study, we identified that inhibitory systems, including inhibitory transmission and transcription of inhibitory receptors, are important for forebrain E-I balance and cognitive experience, and propose a number of potential genes involved in cognition and homeostasis. This study may provide a reference for understanding the homeostatic control of specific types of neuronal activity abnormalities in diseases, including AD and SZ, and also suggest a number of potential candidate genes related to neural homeostasis control and cognition. Ion channels play important roles for homeostatic E-I balance. Previously, overexpression of Kir2.1 in forebrain excitatory neurons in mature neurons, inhibited the excitability of excitatory neurons (Burrone et al., 2002) induce homeostatic plasticity (Harrell et al., 2021) and network re-stable (Burrone et al., 2002; Okada and Matsuda, 2008). In this study, we showed a reduction in neural activity in forebrain excitatory neurons lead to the reduction of inhibitory transmission in Kir2.1 (+) mice. Second, in the hippocampus , spatial training increased the transcription of anion and cation channel-related genes, including cholinergic receptors (Chrna9), voltage-dependent sodium and potassium receptor (Kcne2), calcium receptor (Cacng), chloride ions receptor channel (Clcnka), and GABA receptor (Gabrr). The increasing trend of these receptors is not only consistent with the enhancement of synaptic transmission by spatial training, but may also be related to remodeling of cellular ion homeostasis (including cationic sodium and calcium and anionic chloride ions) and the formation of a new E-I balance after spatial training. Furthermore, artificial inhibition of forebrain excitatory neurons in Kir2.1 (+) mice weakened the transcription levels of anion and cation channel-related proteins, including voltage-dependent calcium, GABA, and sodium receptors, which also supported the weakening of inhibitory synaptic transmission and the change in ion homeostasis in Kir2.1 (+) mice. The reduction of inhibitory transmission is consistent with suppressing pyramidal cell activity reduces inhibitory system (such as parvalbumin cells) in the visual cortex from Kir2.1 overexpression mice (Xue et al., 2014). In addition, these ion channels are often important risk factors for diseases with E-I imbalance, suggesting that the cognitive and homeostasis candidate genes identified in this study may also be targets for diseases characterized by E-I imbalance, such as scn-related channels, which have been associated with Dravet syndrome or other epilepsy syndromes (Meisler et al., 2010). It is suggested that influxed/outfluxed anion and cation or related ion channels may serve as a reference for E-I global homeostatic controlled gene compensation in forebrain, which may also be a mechanism in Dravet syndrome or other epilepsy syndromes. In our study, GABA transmission (mIPSC) homeostatic changes in cognitive experience and E-I balance via disinhibition or inhibition enhancement way in direct interneurons-pyramidal neurons or indirect interneurons-interneurons-pyramidal neurons network. Supporting this conclusion, previous studies have suggested that synaptic transmission of GABA can quickly feedback to abnormal neuronal activity homeostasis in the cortex and plays an important role in maintaining E-I balance (Le Roux et al., 2006; Wilhelm and Wenner, 2008). In trained Kir2.1 (+) mice, the amplitude of mIPSC increased but the amplitude of mEPSC is unchanged and frequency still stay lower level in pyramidal neuron in hippocampus, this unchanged mEPSC may result from neutralizing effect of activity inhibition of pyramidal neuron induced by overexpression of Kir2.1 (+) in forebrain excitatory neurons. Furthermore, in the sequencing results, we mainly compared hippocampal data for a single factor, and also tested and analyzed gene transcription (such as GABA receptors) in the cortex, obtaining ion channel changes similar to those in the hippocampus, which improved the problem of low repetition of sequencing data. Interestingly, the inhibitory system is more likely to be disordered in many diseases, and the resulting E-I imbalance is often an important mechanism in these diseases, such as lots of evidence for primary inhibitory dysfunction in autism spectrum disorders (Gilby and O'Brien, 2013; Nelson and Valakh, 2015), less inhibition linked to SZ (Bhat et al., 2021), parvalbumin cells or parvalbumin cells innervated pyramidal neurons pathway selective degenerated lead to E-I imbalance in AD (Yang et al., 2018). Thus, this study suggests the particularity of the inhibitory system in the process of E-I homeostatic balance and cognitive experience, which is of great significance for subsequent studies of the inhibitory system in this type of disease model. Homeostatic control is essential for adaptation to experience and the accurate regulation of forebrain E-I balance (Turrigiano, 1999; Fong et al., 2015). The forebrain neural networks (Kir2.1 (-) trained) and rebalanced forebrain networks (Kir2.1 (+) trained) may recruit homeostasis to improve the efficiency of cognitive information processing. Although the E-I currents remained in a balanced status in Kir2.1 (+) mice, it recruited evoked IPSCs and mIPSC reduction after Kir2.1 overexpression in the forebrain. And, we suggest that the narrowed neural transmission in Kir2.1 (+) mice may service less bandwidth to processing cognitive information, which supports the impairment of learning and memory in Kir2.1 overexpression mice. Furthermore, spatial training increased neural transmission, such as the amplitude enhancement of mIPSC may be related in part to the increase in transcription of GABAergic, glycinergic and calcium channels related genes after training, which also may increase the bandwidth of cognitive information processing recruited for homeostasis in CA1 from trained Kir2.1 (-) mice compared with that from untrained Kir2.1 (-) mice. Therefore, the level of inhibitory systems (including inhibitory transmission and transcription of inhibitory receptors) that are controlled by homeostasis may be linked to cognitive function. We did not screen out any significant changes in the transcriptome of excitatory receptor, suggesting that different level of mechanisms homeostatic regulating E-I balance. A transcriptome-level mechanism, which may be more sensitive to global regulation of E-I balance via inhibitory system. Another protein-level receptor trafficking mechanism may sensitive to local (such as synapse level) regulation of E-I balance that recruits both excitatory and inhibitory receptors in protein level (Wilhelm and Wenner, 2008; Hou et al., 2011). In this study did not test the total and membrane amounts of glutamate and GABA receptors at the protein level in each group to verify these possible different mechanism. However, we suggested that inhibitory transmission compensation is important for forebrain E-I rebalance and cognitive experience and suggested multiple candidate genes associated with homeostasis and cognitive levels. Conclusion The forebrain excitatory-inhibitory (E-I) homeostatic balance is an important regulator of normal cognition; however, the underlying changes and transcriptomic mechanisms that maintain E-I homeostatic balance and cope with cognitive experiences are largely unknown. This work elucidates that the inhibitory systems, including inhibitory transmission and transcription of inhibitory receptors, are important regulators to forebrain E-I homeostatic balance and cognitive experience, and proposes a number of potential genes involved in cognition and homeostasis. Data availability statement The original contributions presented in the study are publicly available. This data can be found here: Ethics statement The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (SIAT-IACUC-210303-NS-YXA1694). Author contributions TT was the main investigator in this study. YC analyzed the RNA sequencing data. XQ, JW, and YW revised the manuscript. XY designed the study and wrote the manuscript. All authors contributed to the article and approved the submitted version. We thank Jie Lu for critically reviewing this manuscript. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: Click here for additional data file. Click here for additional data file. Click here for additional data file. Supplementary Figure 1 Swimming speed in MWM and travel distance in the open field. Click here for additional data file. 1 References Barron H. Vogels T. Emir U. Makin T. O'Shea J. Clare S. (2016). 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PMC10000299 | Front Plant Sci Front Plant Sci Front. Plant Sci. Frontiers in Plant Science 1664-462X Frontiers Media S.A. 10.3389/fpls.2023.932923 Plant Science Review Harnessing the role of mitogen-activated protein kinases against abiotic stresses in plants Majeed Yasir 1 2 Zhu Xi 1 2 Zhang Ning 2 3 ul-Ain Noor 4 Raza Ali 5 + Haider Fasih Ullah 6 + Si Huaijun 2 3 * 1 College of Agronomy, Gansu Agricultural University, Lanzhou, China 2 State Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou, China 3 College of Life Science and Technology, Gansu Agricultural University, Lanzhou, China 4 Fujian Agricultural and Forestry University (FAFU) and University of Illinois Urbana-Champaign-School of Integrative Biology (UIUC-SIB) Joint Center for Genomics and Biotechnology, Fujian Agriculture and Forestry University, Fuzhou, China 5 College of Agriculture, Fujian Agriculture and Forestry University (FAFU), Fuzhou, Fujian, China 6 College of Resources and Environmental Sciences, Gansu Agricultural University, Lanzhou, China Edited by: Jai Rohila, Agricultural Research Service (USDA), United States Reviewed by: Aayudh Das, The Pennsylvania State University (PSU), United States; Fuai Sun, University of California, Davis, CA, United States *Correspondence: Huaijun Si, [email protected] +ORCID: Ali Raza, orcid.org/0000-0002-5120-2791; Fasih Ullah Haider, orcid.org/0000-0002-2523-8803 This article was submitted to Plant Abiotic Stress, a section of the journal Frontiers in Plant Science 24 2 2023 2023 14 93292326 5 2022 31 1 2023 Copyright (c) 2023 Majeed, Zhu, Zhang, ul-Ain, Raza, Haider and Si 2023 Majeed, Zhu, Zhang, ul-Ain, Raza, Haider and Si This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Crop plants are vulnerable to various biotic and abiotic stresses, whereas plants tend to retain their physiological mechanisms by evolving cellular regulation. To mitigate the adverse effects of abiotic stresses, many defense mechanisms are induced in plants. One of these mechanisms is the mitogen-activated protein kinase (MAPK) cascade, a signaling pathway used in the transduction of extracellular stimuli into intercellular responses. This stress signaling pathway is activated by a series of responses involving MAPKKKs-MAPKKs-MAPKs, consisting of interacting proteins, and their functions depend on the collaboration and activation of one another by phosphorylation. These proteins are key regulators of MAPK in various crop plants under abiotic stress conditions and also related to hormonal responses. It is revealed that in response to stress signaling, MAPKs are characterized as multigenic families and elaborate the specific stimuli transformation as well as the antioxidant regulation system. This pathway is directed by the framework of proteins and stopping domains confer the related associates with unique structure and functions. Early studies of plant MAPKs focused on their functions in model plants. Based on the results of whole-genome sequencing, many MAPKs have been identified in plants, such as Arbodiposis, tomato, potato, alfalfa, poplar, rice, wheat, maize, and apple. In this review, we summarized the recent work on MAPK response to abiotic stress and the classification of MAPK cascade in crop plants. Moreover, we highlighted the modern research methodologies such as transcriptomics, proteomics, CRISPR/Cas technology, and epigenetic studies, which proposed, identified, and characterized the novel genes associated with MAPKs and their role in plants under abiotic stress conditions. In-silico-based identification of novel MAPK genes also facilitates future research on MAPK cascade identification and function in crop plants under various stress conditions. abiotic stresses climate change plant physiology signaling pathway stress tolerance transcription factor National Natural Science Foundation of China 10.13039/501100001809 31960444 Gansu Agricultural University 10.13039/501100007932 GSCS-2019-Z03 The research program was sponsored by the National Natural Science Foundation of China (No. 31960444), the Gansu Provincial Key Laboratory of Aridland Crop Science, Gansu Agricultural University (No. GSCS-2019-Z03), and the Gansu Major Science and Technology Project (No. GZGG-2021-6). pmc1 Introduction One of the sustainable development goals is to end world hunger, and feeding a growing population is a significant worldwide societal concern (Raza et al., 2021; Farooq et al., 2022; Rivero et al., 2022). Despite the world's population doubling, the long-term drop in global undernourishment has been caused by a substantial rise in food availability since 1960 (Ritchie and Roser, 2020). Nevertheless, there are currently more than 820 million hungry people around the globe (FAO et al., 2019). Only 9% of the world's agricultural land is suitable for growing crops, while the remaining 91% is subjected to abiotic stress, which frequently occurs in combination. Abiotic stresses cause losses in agricultural productivity of more than 50% (Raza, 2021; Rivero et al., 2022). Still, due to climate change and the overuse of natural resources, their severity and adverse effects are anticipated to increase significantly, which not only reduce crop production but also cause food insecurity in the near future (Minhas et al., 2017; Farooq et al., 2022; Rivero et al., 2022). Due to industrialization and climate change in recent decades, plants are normally exposed to various abiotic stresses such as drought, salinity, extreme temperature ranges, nutrient deficiency, high heavy metal concentrations, and osmosis stress (Haider et al., 2021; Raza et al., 2021; Raza et al., 2022a; Raza et al., 2022b; Raza et al., 2022c; Raza et al., 2022d; Raza et al., 2022e). They cause a lot of damage to plants' physiology and also reduce growth and development that ultimately minimizes the productivity of crop plants (Anjum et al., 2017). To ensure good crop growth and optimum productivity, stress tolerance mechanisms are imperative to be studied for combating abiotic stresses in crop plants (Baer-Nawrocka and Sadowski, 2019; Raza et al., 2022a; Raza et al., 2022b; Raza et al., 2022c). Understanding these stress tolerance mechanisms will enable the generation of more climate-smart and stress-tolerant lines, which will maintain stability in the growth and productivity of agricultural productivity. For this, it is necessary to understand the genetic basis of a plant's interaction when encountering ecological stress. Several studies considering transcriptomics, genomics, proteomics, metabolomics, and genome editing via CRISPR/Cas technology provide a roadmap toward the acclimatization mechanism in plants and crops (Wang et al., 2019; Raza et al., 2022a; Raza et al., 2022b; Raza et al., 2022c; Raza et al., 2022d; Yaqoob et al., 2023). In-depth molecular studies aid us in developing varieties and cultivars through biotechnology, genetic engineering, and other advanced breeding methods to develop plants that could adapt to different abiotic stresses in a short time (Popescu et al., 2009; Raza et al., 2022a; Raza et al., 2022b; Yaqoob et al., 2023). Post-translational modification and signal transduction are mediated by a process called phosphorylation, which changes the expression of genes through transmission of protein signals. A serine/threonine-protein kinase family called mitogen-activated protein kinase (MAPK) is one of the widely studied gene families and contributes to plant productivity under fluctuating environmental conditions (Hamel et al., 2006). In this regard, one of the major signal transduction pathways that transduce extracellular stimuli into intracellular responses related to stress is mitogen-activated protein kinase (Mathobo et al., 2017). The first MAPK encoding gene was cloned in the 1990s; to date, many MAPK genes have been identified and isolated from different plants (Zaidi et al., 2010), which are activated under abiotic stresses like AtMPK4 and AtMPK6 in Arabidopsis and in rice (Oryza sativa) and OsMAPK5 and OsMAPK2 under drought stress (Nadarajah and Sidek, 2010). The abscisic acid (ABA) signaling pathway regulates plant growth and development under abiotic stress conditions, such as drought or high salinity (Cutler et al., 2010). Phosphorylation of two ABA-responsive transcription factors (ABF1 and ABF4) by AtCPK4, 11, and 32 suggested the role of kinases in regulating ABA signaling through these transcription factors under stress conditions (Choi et al., 2005). Using a yeast two-hybrid test, researchers looked at the interactions between 30 members of the MPK family, 9 CPKs, 8 PP2Cs, 5 SnRKs, and 8 PP2Cs in maize's (Zea mays) MAPK signaling pathways. Moreover, three ZmCPKs connect with three distinct ZmSnRK members, whereas four ZmCPK members positively interact with 13 different ZmMPK members in various combinations. These four ZmCPK proteins originate from three distinct maize groupings. These physical connections between ZmCPKs, ZmSnRKs, and ZmMPKs revealed that these signaling pathways might interact directly with the defense mechanism in maize and have indirect effects. The current work might contribute to a better understanding of plant signal transduction (Khalid et al., 2019). Concerning the downregulation of ZmMPK5, due to ZmCPK11 silencing, the role of ZmCPK11 upstream of ZmMPK5 has been proposed (Ding et al., 2013). MAPK gene families consist of a vast number of genes that are classified into four different groups: A, B, C, and D. Owing to the evolutionary divergence in different plants, these groups contain a different number of MAPK genes; some of them are listed in Figure 1 and Table 1 . This MAPK signaling cascade works like a chain reaction as mitogen-activated protein kinsase kinase (MAPKK) is activated by the upstream of the mitogen-activated kinase (MAPKKK), which, in turn, activates the mitogen-activated protein kinase (MAPK) (Wang et al., 2014; Mitula et al., 2015). This full chain of MAPKs is conserved in plants, which signifies the evolutionary perspective of MAPKs. One of the most important methods that is triggered by posttranslational modification of signal transduction is called phosphorylation (Wang et al., 2019). MAPKKK phosphorylates MAPKK on the conserved serine/threonine motifs (Rodriguez et al., 2010), which finally brings about the phosphorylation of TXY (T is threonine, Y is tyrosine, and X is any amino acid) in MAPKs (Taj et al., 2010). Figure 1 (A) Phylogenetic analysis of plant mitogen-activated protein kinases (MAPKs) and MAPK-likes in 13 plant species following Bayesian inference. Different colors indicate different species. The monocot clade and the PP sequence with the atypical MEY activation loop within the TEY-B clade are marked by asterisks. (B) Phylogenetic analysis of MAPKKKs in grapevine, apple, tomato, and Arabidopsis using the neighbor-joining (NJ) tree using MEGA-X with 1,000 bootstraps. Adapted from He et al. (2020) and Janitza et al. (2012), open-access articles distributed under the terms of the Creative Commons Attribution License (CC BY). Table 1 Identification of groups of MAPK gene families in different plant species. Plant species Group A Group B Group C Group D Total References Arabidopsis 3 5 4 8 20 Ccakir and Kilicckaya (2015) Rice 2 1 2 10 15 Reyna and Yang (2006) Wheat 11 13 22 63 109 Lian et al. (2012) Maize 7 7 6 19 39 Wang et al. (2010) Cotton 4 6 5 12 27 Wang et al. (2016) Poplar 4 4 4 9 21 Zhao et al. (2018) Tomato 3 4 2 7 16 Kong et al. (2012) Apple 5 6 5 10 26 Zhang et al. (2013) Potato 1 4 2 8 15 Zaynab et al. (2021) Transcription factors and downstream kinases activate the cell after receiving extracellular signals from the activated MAPKs, which describe the variation of the cellular development factors (Zhang et al., 2018). The process of transmission and amplification of signals occurs in stepwise phosphorylation (Hamel et al., 2006). When plants are encountered by any abiotic stress or wounding, MAPK, as well as other hormones like ethylene, jasmonic acid, and salicylic acid, are activated. Studies also suggested that pathogen stimuli also cause the induction of MAPKs in various plants like alfalfa (Medicago sativa), rice (Orzya sativa), maize (Z. mays), and potato (Solanum tuberosum) (Andrasi et al., 2019). Under adverse environmental conditions like high temperature and water scarcity, MAPKs play a key role in signal transduction (Muhammad et al., 2019). Studies also have revealed that MAPK cascade is also activated under salt stress and freezing temperature (Teige et al., 2004). Shreds of evidence provide the signaling activation of MAPKs during early wounding in different plants such as Arbodiposis, apple (Malus hupehensis), poplar (Populous alba), and rice, as reported previously (Takahashi et al., 2011). Recently, many MAPK genes have been identified, which play a role under various stress conditions, but there is little knowledge on the molecular mechanisms of MAPK triggering and signaling (Mohanta et al., 2015). The available knowledge about the molecular characterization of the MAPK gene family under abiotic stress is summarized owing to need for more information about MAPK signaling and triggering in many crops. In this review, we will focus on the action of transcription factors, transcriptomic studies, and the molecular basis for understanding the biological, biochemical, and physiological processes of different plants under abiotic stresses. Furthermore, we summarized the classification of different MAPK gene families in response to abiotic stress in plants and molecular and cellular signaling pathways in plants for acclimatization under an adverse environment. After all, many phosphorylated MAPKs play a role in signal transmission. In short, incorporating MAPK gene families in plant breeding to produce stress-smart varieties is another aspect of research in MAPKs. This review may help to comprehend the ecological importance of MAPKs in plants to overcome the abiotic stresses for sustainable crop production and also provide new insights for breeders to incorporate MAPK gene families in plant breeding program to produce abiotic stress resistance varieties. 2 Mechanism of MAPKs in crop plants Plants have acquired different acclimatization strategies under harsh environmental conditions over time via a number of molecular systems that consist of sensing, signaling, and expression under stress conditions by stress-responsive genes (Mahmood et al., 2020). MAPKs are one of the tools that regulate growth and development, cell division, proliferation, apoptosis, hormonal response, and other stress responses by an extremely conserved network. It consists of the three protein kinases MAPK, MAPKK, and MAPKKK. Sequential phosphorylation activates these cascades such as activation of MAPKKK phosphorylates the S/T-X (S/T is a serine/threonine and X is an arbitrary amino acid) conserved motif that is present in the activation loop of MAPKK (Rodriguez et al., 2010); then, the activation of MAPKK phosphorylates the T-X-Y (T is threonine, Y is tyrosine, and X is any amino acid) in the variant motif present in the activation loop of MAPK (Taj et al., 2010). Then, these MAPK cascades send the message in a well-designed manner to the primary genes responsive to tolerance and then to secondary genes, which induce tolerance in crops under stress conditions (Hamel et al., 2006). The MAPK cascades are also phosphorylated by the following activities such as regulation of microtubule proteins, cytoskeletal activities, and other transcription factors that help in numerous responses and phospholipases (Danquah et al., 2014). The transmission of extracellular stimuli into cells and downstream kinases is also activated by MAPK cascades (Xu et al., 2010). The main channel of signal transduction and post-transcriptional modification is carried out by phosphorylation. The process of phosphorylation is a post-translational modification process that alters the expression of downstream genes as well as diffuses and intensifies the external signals (Colcombet and Hirt, 2008). One of the wide-ranging gene families is the serine/threonine protein kinase family of MAPKs, which are protein kinases and are enzymatic in nature and mediate phosphorylation (Rodriguez et al., 2010; Xu et al., 2010). Conventionally, MAPK cascades transmit signals downstream by the activation of the stimulated receptors of the cell membrane (Wang et al., 2014). By following this mechanism, MAPKs, after activation, control the expression of many genes and proteins by the phosphorylation of transcription factors. This mechanism in plants plays a key role in cell differentiation, cell growth, development, and hormonal movement, and in response to various biotic and abiotic stresses (Komis et al., 2018). In crop species, the MAPK gene families are recognized owing to the many tolerant genes in abiotic stress response, evident from genetic studies of MAPK activity in recent years (SSamajovai et al., 2013). The MAPK mechanism is depicted in Figure 2 , where extracellular signals are detected by a plasma membrane and by sensors in cytoplasm, which act like a chain reaction, leading to the activation of MAPKKK and, subsequently, MAPKK and, as a result, phosphorylation of MAPK, which helps in the phosphorylation of proteins, enzymes, and post-transcriptional factors in the nucleus. These factors finally send a message to stress-tolerant responsive genes (Bigeard and Hirt, 2018; Singh et al., 2019). By understanding this novel mechanism, MAPK genes can be identified in different crop plants, which may help in maintaining plant growth under various abiotic stress conditions, but still, there is a limitation due to the activation of other intricate stress responsive mechanisms. Figure 2 The receptors after receiving the signals activate the specific mitogen-activated protein kinase (MAPK) proteins that are inactive before. Subsequently, MAP4K activates other MAPKs (including MAP2K and MAP3K) by phosphorylating the ST (S/T is serine/threonine) and TXY (T is threonine, Y is tyrosine, and X is any amino acid) motif in MAPKs (Rodriguez et al., 2010; Taj et al., 2010). As a result, MAPKs activate the transcription factors (TFs), enzymes, and other downstream kinases that transmit extracellular environmental signals to the cells that play a role in growth, development, stress response, and other physiological and biochemical processes (Zhang et al., 2018). 3 MAPK complexity in abiotic stress signaling interaction Abiotic stresses, such as drought, cold, heat, salinity, and metals, are closely associated with an adverse influence on the physiology of plants (Krasensky and Jonak, 2012; Raza, 2021; Raza et al., 2021; Raza et al., 2022a; Raza et al., 2022b; Raza et al., 2022c; Raza et al., 2022d). For example, when the temperature rises, water deficiency, salinity, and osmotic pressure in the tissues of plants may be encountered (Bita and Gerats, 2013). Likewise, due to salinity and water scarcity, plants suffer from osmotic stress, and signaling molecules are activated in response to stress conditions (Rengasamy, 2006). The mechanism of expression of resistance genes in various plants like maize (Z. mays), rice (O. sativa), potato (S. tuberosum), and Arabidopsis is regulated under various abiotic stress conditions, which are activated by messenger-mediated signal transduction (Zhu, 2016; Zandalinas et al., 2019). The large numbers of stress-responsive genes like MAPK genes or MAPK cascades participate in a variety of abiotic stresses for the protection and survival of plants (Ji et al., 2017; Yanagawa et al., 2017). MAPK gene families have multiple functions in plants, such as growth and development, immune defense system, and response to biotic and abiotic stresses. Certain studies also point toward the role of MAPK cascade in the regulation of cell death and defense responses (Qiu et al., 2008; Zhou et al., 2017). Recently, it was also reported that MAPK cascade has a dual function in plant immunity: the basal resistance is regulated positively and immunity regulation is facilitated negatively by kinase protein (Zhang et al., 2012). One case reported in Arabidopsis also provides evidence that MAPKs play a vital role in pathogen signaling (Doczi et al., 2007). Furthermore, MAPK cascade mediates Ca2+ reactive oxygen species (ROS) by signaling during early wounding (Pitzschke and Hirt, 2009). MAPK pathways regulate the synthesis of ROS, and certain genes of MAPKs are induced by ROS generation (Colcombet and Hirt, 2008). H2O2 also plays a key role in activating orthologs of MAPKs in many crops like tobacco (Nicotiana tobacum) and Arabidopsis (Xing et al., 2008). MAPK cascade in Arabidopsis regulates H2O2 metabolism (Nakagami et al., 2006), and in tobacco, it is an important component in ROS metabolism (Ning et al., 2010). In maize, H2O2 induces transcription and expression of MAPK cascade, whereas in tobacco, it protects against ROS-mediated injury under osmotic stress (Zhang et al., 2010; Kong et al., 2011). This is due to the different expression patterns of MAPK gene families under different stresses in different plant species. In maize, the MAPK network works as an early signaling response by regulating the production of ROS in plants subjected to drought stress (Gao and Xiang, 2008). In later developmental stages, one MAPKKK gene called MAPKKK20 in Arabidopsis improves salt tolerance (Jammes et al., 2009). Similarly, water loss by transpiration in the Arabidopsis double mutant named MPK9/MPK12 is less as compared to its wild type. Moreover, it was also documented that ABA regulates the physiological response under abiotic stress (Tajdel et al., 2016). In Arabidopsis, one MAPKKK gene named MAPKKK18 shows reduced stomatal opening under normal conditions in mutant plants (Mitula et al., 2015). Furthermore, this mutant also shows ABA-induced stomatal closure, which shows that MAPKKK18 is directly interacting with ABA components, which plays a key role in signal modulation as SnRK2-6 kinase and PP2C phosphatase ABI1 (Zhang et al., 2006). An increment of ABA in plants is an indication of oxidative stress. An abnormal level of ROS causes the oxidation of free radicals such as hydrogen peroxides, which is called oxidative stress and leads to the injury of cells and tissues. The MAPK gene families reinfoirces the ABA-induced antioxidant defense system by decreasing the ROS production in many crops like maize (Shi et al., 2011). Under physiological and biochemical conditions of abiotic stresses, the intricate role of kinase proteins by signal transduction of MAPKs still has research gaps. It is required to associate the link between MAPKs and their corresponding stress in vivo. In the future, further functional analysis on MAPK members for physiological and biochemical roles in stress management can be helpful in breeding programs for innovation and advancement of agricultural science. 4 Role of MAPKs under abiotic stresses Plants often experience various abiotic stresses (drought, low and high temperature, salinity, osmotic, etc.), which significantly affect their growth, productivity, and nutritional quality (Yu et al., 2019; Sun et al., 2020; Raza, 2021; Raza et al., 2021; Raza et al., 2022a; Raza et al., 2022b; Raza et al., 2022c; Raza et al., 2022d). The role of MAPKs against various abiotic stresses are briefly discussed in the subsequent sections. 4.1 The role of MAPKs under drought and oxidative stress Drought stress is a major environmental factor affecting crops' growth and productivity, leading to significant socioeconomic damage (Sinha et al., 2011; Zhang et al., 2018; Raza et al., 2022a). Drought occurs when water uptake within the plant by root is reduced due to low moisture in the soil, afflicting root morphology growth and physiology owing to wilt conditions, and consequently reducing the annual yield in plants (Aditi et al., 2020; Ahmad et al., 2021; Feng et al., 2022; Lu et al., 2022; Raza et al., 2022a). Biochemical and transcriptional studies have elaborated the MAPK response in drought in grassy and woody plants (Huang et al., 2020). Recently, it was studied that the MAPK cascade was induced with Arbuscular mycorrhizal fungi (AMF) inoculation in apple (Malus hupehensis) seedling following increased expression level of MAPKs such as MdMAPK16-2, MdMAPK17, and MdMAPK20-1 by 36.93%, 58.14%, and 54.14%, respectively, compared to those that do not have AMF inoculation (Xu and Chua, 2012). By regulating the RNA de-capping process in Arabidopsis, MAK6 improves the tolerance to dehydration (Hua et al., 2006). In Arabidopsis, MAPK gene families are activated. The promoter RD29, which is a dehydration-responsive gene via transient expression assay, suggests that MAPK cascade plays a vital role in drought signaling (Zaheer and Akhtar, 2016). In Arabidopsis, the transcriptional regulation of 44 MAPKs has been identified, out of which some are induced by water stress such as MPK2, MPK4, MPK5, MPK12, and MAPKKK4 (Moustafa et al., 2014). Potato (S. tuberosum L.) is known as one of the drought-sensitive crops, and serious yield loss has been threatened by drought stress (Handayani et al., 2019; Sattar et al., 2021), as well as lessened the quality of potato crops (Iftikhar et al., 2017). Studies revealed that 108 MAPK protein-coding genes have been found in potatoes (Zhu et al., 2021). More recent studies confirmed that 22 MAPK genes had been reported in the potato genome, such as StMAPK1 to StMAPK22 (Zaynab et al., 2021; Zhu et al., 2021), of which, six MAPKs have been related to abiotic stress, as well as six types of plants hormones (Boguszewska-Mankowska et al., 2020). StMAPK11 response is well studied for drought stress in potato, and it shows reasonable drought tolerance in potato when subjected under drought conditions (Zhu et al., 2021). The drought sensitivity of potato is due to the shallow root system that cannot explore the moisture from the deeper soil layers (Kumar et al., 2008). Further studies related to the characterization of MAPKs in drought stress can help improve the gene expression and physiology of potato. Many MAPKs related to drought stress tolerance are also observed in rice such as MAPKKK protein drought-hypersensitive mutant1 (DSM1), which shows reduced ROS generation under water-stressed conditions and increases the survival of plants under drought stress (Gao and Xiang, 2008). Overexpression of OsMAPK5, which is an ortholog of Arabidopsis MAPK3, also acts as a drought-responsive gene. Studies also suggested that the OsMAPK2 responds to drought stress and salt stress signaling within 15 min in rice crops, as shown in Figure 3 (Popescu et al., 2009). Figure 3 The schematic diagram of different mitogen-activated protein kinase (MAPK) signaling molecules under different stress conditions in different crops. Solid arrows show verified pathways; dashed arrows indicate assumed pathways; question marks indicate unknown cascade components. Mostly abiotic stresses such as drought, cold, heat, and osmotic stress interrupt the metabolic equilibrium of the cell, which causes oxidative stress (Gill and Tuteja, 2010; Mittler et al., 2022; Raza et al., 2022b). The abnormal level of ROS such as free radicals and non-radicals leads to damage of specific molecules, which injured the cells or tissues in broad terms. It is called oxidative stress, which is due to the oxidation of molecules (Xing et al., 2007; Mittler et al., 2022). Antioxidants like endogenous or exogenous compounds help in the removal of ROS. Scavenger enzymes in plants like catalase decompose H2O2 and overcome oxidative stress. ABA regulates the A. thaliana CAT1, and MAPKK inhibitor PD98059 delayed CAT1 expression, which is mediated by ABA signaling (Ning et al., 2010). Under dehydration stress, the MKK1 and MPK6 mutant in A. thaliana alter their response to ABA. It was proposed from the above findings that MKKI-MPK6 controls the metabolism of H2O2 by CAT1 with the absence of ABA-mediated activation of MPK6 and MMKI (Nakagami et al., 2006). Plant defense mechanism and salicylic acid (SA) accumulation are controlled by the CAT2 expression, which is stimulated by MEKK1 and MPK4 (Colcombet and Hirt, 2008). ROS metabolism is regulated by the MEKK1-MPK4 pathways (Ning et al., 2010). Many other MPAKKKs in A. thaliana are activated by H2O2, such as ANPI, which causes the downstream activation of MPK3 and MPK6, as shown in Figure 3 (Ding et al., 2009). These findings suggest that MAPKs not only are induced by ROS but also control ROS and arbitrate oxidative stress in crops. Oxidative stress is a communal response under abiotic and biotic stress as ROS is a conjunction point to indicate the stress in plants. Recently, ROS-mediated MAPK signaling in plants has been described. In A. thaliana mutants, MAPK studies reveal the specific protein association related to ROS control (Ning et al., 2010). The significant roles of MAPK genes in different crops like alfalfa (M. sativa), rice (O. sativa), cotton (Gossypium hirsutum), maize (Z. mays), apple (Malus hupehensis), potato (S. tuberosum), cucumber (Cucumis sativus), strawberry (Fragaria vesca), mulberry (Moraceaemorus), and cassava (Manihot esculenta) under drought condition are mentioned in Table 2 . From the above discussion, it is concluded that many MAPK gene families in different crops integrate stress-related proteins and regulate stimulus response. It is necessary to identify and isolate more MAPK genes for crop improvement. Table 2 MAPK gene signaling responses in different plants under drought stress conditions. Plant species MAPK genes Activation Plant stage References Arabidopsis AtMPK2, AtMPK3, AtMPK4, AtMPK5, AtMPK12, and AtMKK Activated at the transcriptional level Activated by promoter RD29 under dehydration Seedling Chen et al. (2015) Alfalfa MsP44, MsMKK4 Activated at the post-transcriptional level Seedlings Chen et al. (2015) Rice OsMPK3,4 Activated by the regulation of protein DSM1 (drought-sensitive mutant1) Seedling Huang et al. (2020) OsMKK6 Transcriptionally regulated by drought Seedling Huang et al. (2020) OsDSM1 Gao and Xiang (2008) OsMSRMK2,5 and OsMAPKK1 Activated under combined drought and osmotic stress Seedling Wang et al. (2010); Chen et al. (2015) Cotton GhMAPK2, GhMAPK16 Activated under combined drought and osmotic stress Germination Wang et al. (2007) Maize ZmMPK2 Activated under reducing water and osmotic pressure Seedling Zhang et al. (2011) Apple MaMPK Activated at the transcriptional level Seedling Sun et al. (2017) Potato StMAPK11 Activated by induction of drought and hormone stress Flowering Zhu et al. (2021) Cucumber CsMAPKs Activated by the regulation of stress-associated genes and drought stress Flowering Wei et al. (2014) Strawberry FvMAPK5,8 Activated at the transcriptional level Reproductive Zhou et al. (2014) Mulberry MnMAPK1, MnMAPK2 Negatively activated by drought stress Reproductive Yan et al. (2016) Cassava MeMAPK Activated 20% in leaves and 70% in roots under high drought conditions Flowering Chinnusamy et al. (2007) 4.2 The role of MAPKs under cold stress One of the most critical factors that affect the growth and development of crops is cold stress or chilling temperatures like sudden frost and snow, and freezing temperatures cause serious damage to crop production and quality (Raza et al., 2021; Ma et al., 2022; Raza et al., 2022c). When plants survive under cold or freezing temperatures, it is called cold tolerance or winter hardiness (Peng et al., 2006). The physiological and metabolic status of crops is changed by the altered expression of many genes during cold acclimatization (Agarwal et al., 2010; Medina et al., 2016; Raza et al., 2021; Raza et al., 2022a; Raza et al., 2022c). In Arabidopsis, MAPK genes like MEKK1, MKK2, MPK4, and MPK6 were shown to be activated under cold stress (Teige et al., 2004). The cold-sensitive gene MKK2 does not have any effect on MPK4 or MPK6, which suggests that MKK2 is an upregulator of MPK4 and MPK6 in low temperature. This outcome shows that chilling temperature activates MEKK1, MPK3, MPK4, and MPK6 (Krasensky and Jonak, 2012). Another MAPKK gene named SbMAPKK in halophytes, such as sea bean (Salicornia brachiate), shows upregulation under cold stress (Meng and Zhang, 2013), because cold as well as salt stress induces some kinase molecules that allow plants to survive under adverse environments. Recently, in tomato, CRISPR/Cas9-mediated SlMAPK3 mutants were used to investigate the relationship between ferulic acid (FA) and SlMAPK3 under chilling temperatures. It was shown that under low temperature, i.e., 4degC, FA content increases, which then increases the FA synthesis-related gene (SlPAL5, SlC3H, and SlCOMT) expression. However, the knockout of SlMAPK3 inhibited the content of FA and the expression of those genes compared with the control, which suggested a close relationship between SlMAPK3 and FA. Plant response to cold stress depends heavily on the CBF/DREB1 (C-repeat binding factor/dehydration resistance element binding protein 1)- and ICE1 (inducer of CBF expression1)-dependent transcriptional regulatory mechanisms. It has been demonstrated that CBFs may bind to cis elements in the COR (COLD RESPONSIVE) gene promoters, sufficiently activating the expression of COR genes and inducing resistance to cold stress. It was revealed that the FA in tomato fruit provides resistance to chilling stress by upregulating the gene expression of the repeat binding transcription factor (CBF), a transcriptional pathway, in a MAPK3-dependent manner (Shu et al., 2022). Under cold stress, MKK4/5-MPK3/6 and MEKK1-MKK1/2-MPK4, the two MAPK gene mutants, show response to external stimuli produced by cold stress (Furuya et al., 2013; Pitzschke et al., 2014). It is also documented that MEKK1-MKK2-MPK4/MPK6 pathways positively regulate the cold response and chilling temperature tolerance in Arabidopsis (Teige et al., 2004). To induce the kinase mechanism, MKK2 activity is phosphorylated by MEKK1 under cold conditions (Raina et al., 2013), which further activates MKK2 that phosphorylates MPK4 and MPK6 (Teige et al., 2004), likely adjusting downstream molecules to regulate the cellular status. These findings showed that the MMK2 pathway regulates the freezing response (Teige et al., 2004). SlMPK3 upregulates the growth of tomato under low temperature (Yu et al., 2015). In potatoes, it is reported that the MAPK3 showed a response under cold stress (Zhang et al., 2017) and chilling temperature stress (Xie et al., 2012). MAPK3 also activates the phosphorylation downstream for ACC synthase and transcriptional factor OsbHLH002/OsICE1 for chilling outbreaks (Xie et al., 2012). Under cold stress, MKK2-MPK4/MPK6 cascades are activated (Teige et al., 2004). In recent years, the MAPK genes in rice OsMKK6-OsMPK3 have been identified, which are activated in cold stress (Fu et al., 2012). cDNA library screening revealed another well-studied MAPKK gene OsMEK1 that showed interaction with OsMAP1, which is important in freezing temperature tolerance (An et al., 2012). Under cold stress, the MPKK genes ZmMKK4 (Wu et al., 2011) and ZmMPK7, as shown in Figure 3 (Osthoff et al., 2019), showed upregulation in maize. These two genes are found in the nucleus and control the transcription factors at low temperature. Similarly, five more MAPKs have been identified, which responds positively in roots of maize under cold stress (Osthoff et al., 2019). It is described that the seedlings of cotton at low temperature (4degC) showed optimum growth against cold stress, especially in root cells because of the over-expression of the MAPK gene named GhMAPK (Zhang et al., 2011). MAPK genes in different crops like Arabidopsis, alfalfa, blue mustard (Chorispora Bungeana), cotton, maize, rice, and sea bean (Salicornia brachiate) under cold and heat stress conditions are mentioned in Table 3 . Cold stress causes severe damage in many regions of the world. Therefore, research should incorporate MAPK cascades with the help of modern technologies in breeding resistance cultivars of different crops by identifying novel MAPK gene families. Table 3 MAPK gene signaling responses in different plants under cold and heat stress conditions. Plant species MAPK genes Activation References Cold Arabidopsis AtMEKK1,6 Calcium-dependent activation, to regulate vacuolar processing enzyme (VPE) Zhang et al. (2006) AtMPK1,6 MKK2 is the upstream activator of MPK4 and MPK6 Zhang et al. (2018) AtMAPKK, AtMKK2 Alfalfa MsSAMK, MsP44MKK4 Activated by cold shock domain-containing proteins (CSDPs) Agarwal et al. (2010) Blue mustard CbMAPK3 Activated under low temperature Nakagami et al. (2005) Cotton GhMAPK, GhMAPK2, 7 Activated under 4degC Yang et al. (2019) Maize ZmMPK3,5 Activated under high accumulation of proline Zhang et al. (2011) ZmMPK17 Activated under chilling conditions Kong et al. (2011) Rice OsMSRMK2 Activated at 12degC Meng and Zhang (2013) OsMAPKK2, 4,6 and 10 Activated by low temperature stress at the transcriptional level OsMKK6, OsMPK3 Activated by cold shock domain-containing proteins (CSDPs) Xie et al. (2012) OsMAPK5 Activation under chilling temperature Xiong and Yang, 2003 Sea bean SbMAPKK Activated by cold shock domain-containing proteins (CSDPs) Meng and Zhang (2013) Tomato SlMPK3 Upregulation under low temperature Yu et al. (2015) Heat Rice OsMKK4,6 Activated when temperature increased from 37degC Wen et al. (2002); Kumar et al. (2008) OsMSRMK2 Activated at high temperature < 37degC Agrawal et al. (2002) Alfalfa MsHAMK Activated by the activation of heat shock protein. Sangwan et al. (2002) Potato StMPK1 Activated by high temperature stress at the transcriptional level Blanco et al. (2006) Cucumber CsMKK4 Activated by the upregulation of heat shock transcription factors (HSFs) Wei et al. (2014) Strawberry FvMAPKK3 Activated by the upregulation of HSFs Lohani et al. (2020) Mulberry MnMAPK1,5,6 Activated at 40degC under high temperature Yan et al. (2016) Tomato SlMPK1 Negitively regulated under high temperature Ding et al., 2018 4.3 The role of MAPKs under heat stress Temperature is considered the most essential factor to achieve optimum metabolic processes, growth, development, and production of plants (Yin et al., 2014; Haider et al., 2022; Raza et al., 2022c). The amount of water in cells under different temperatures is a fundamental feature for cell survival, which is directly proportional to plant growth and damages the cell structure and organelles and reduces productivity (Jiang et al., 2015; Xing et al., 2015; Raza et al., 2021). High temperature also causes overproduction of ROS due to the high rate of respiration and photosynthesis, which significantly affects the growth and development of plants (Li et al., 2012). MAPKs play an important role under heat stress in plants such as aspen (Brachypodium distachyon); 60% of genes activated under high temperature by MAPKs signal transduction cascade (Suri and Dhindsa, 2008). To date, few studies about heat stress signaling of MAPKs provide evidence that only specific MAPKs are upregulated or activated under high temperature stress (Munns et al., 2020). It has been experimentally proven that MAPK3 is activated under heat stress and ultra-irradiation and helps to mitigate stress by controlling the growth of plants (Tuteja, 2007). Secondly, the heat shock protein HSP70 plays a vital role in response to heat stress signaling through the HSP gene by the activation of the MAPK named HAMK in tobacco (Wei et al., 2014). In cucumber (C. sativus), an MAPK gene named CsMKK4 is activated after 8 h of heat treatment. Most of the MAPK genes showed activation under heat stress except CsMPK3 and CsMPK7 (Wei et al., 2014). The upregulated transcript level of FvMAPK3, FvMAPKK1, FvMAPKK3, FvMAPKK6, and FvMAPKK7 in strawberry (F. vesca) has been observed under high temperature (Zhou et al., 2014). In the same way, under heat stress, the gene named FvMAPKK3 is activated (Zhou et al., 2014). In mulberry (morus) under heat stress, eight MAPK genes have been identified, which showed upregulation (MnMAPK1, MnMAPK5, MnMAPK6, and MnMAPK9) and downregulation (MnMAPK2, MnMAPK3, MnMAPK8, and MnMAPK10) (Yan et al., 2016). Likewise, under high temperature, the downward growth regulation of the tomato gene named SlMPK1 is shown (Ding et al., 2018). The above studies indicated that under heat stress conditions, MAPK cascade is regulated in plants. MAPK gene families related to heat resistance is negligible; due to climate change, this stress will be a severe threat in coming years. This stress can be overcome by identifying desirable MAPK gene families in commercial crops. 4.4 The role of MAPKs under salinity and osmotic stress In plants, there are three major salt tolerance mechanisms, namely, osmotic pressure tolerance, ionic balance management, and decreasing the Na+ and concentrations (Mohamed et al., 2022; Raza et al., 2022d). Salinity stress is a very serious threat in many regions of the world; more than 50% of irrigated soils all over the world face reduction in the productivity of major agricultural crops (Shi et al., 2010). Under salt stress, cell membrane and protein disruption occurs due to the overproduction of ROS in plants, which is one of serious problems for crops grown under salt conditions (Nakagami et al., 2005; Raza et al., 2022d). It was also reported that MAPK proteins are activated when plants are subjected to salt stress; this leads to speeding up the expression level of V-H+-ATPase, which increases the tolerance to salinity stress (Krasensky and Jonak, 2012). In Arabidopsis, a MAPKK gene named MEKK1 mRNA accumulated in response to high salt stress. The protein-protein interaction between MMK2/MEK1 and MPK4 MAPKs, MMK21 and MKK2/MEK1 MAPKKs, and MPK4 and MEKK1 was shown by yeast two-hybrid analysis (Teige et al., 2004). It was also documented that salt stress signal transmission occurred at two MAPK cascades such as MPK4 MAPK cascade with genes named MEKK1-MEK1/MKK2-MPK4 and MPK6 and a second MAPK cascade with a gene named p44MAPK involved in salt tolerance in Arabidopsis, as shown in Table 4 . MEKK1 involve as more upstream of MKK2 and more downstream MAPKs MPK4 and MPK6 under salinity stress (Teige et al., 2004). MAKs such as MPK6, MPK4, and MKP1 play a negative role under salinity stress conditions (Faried et al., 2017). A salt stress-induced MAPK named 46kDa SIMK showed response under salt stress in alfalfa (Krasensky and Jonak, 2012). In vivo as well as in vitro tolerance to salt stress produced by upstream kinase named SIMKK intermingles with SIMK by yeast two-hybrid (Krasensky and Jonak, 2012). Table 4 MAPK gene signaling responses in different plants under salinity stress. Plant species MAPK genes Activation Concentration References Arabidopsis AtMEKK1,2 Activation by accumulation of sodium chloride High salt accumulation Teige et al. (2004); Moustafa et al. (2008) AtMPK1,3 Activation of RD29A and RD29B gene promoters Excess of salts Yu et al. (2010) AtMPK4,6 Activated by phosphatidic acid (PA) Acid accumulation Moustafa et al. (2008) Maize ZmMPK3,5 Activated under very high salt concentration High amount of salts Wang et al. (2010) ZmSIMK1 Activated by high salinity Higher salt accumulation Gu et al. (2010) ZmMKK4 Activated by NaCl accumulation Excess amount of NaCl Kong et al. (2011) Rice OsMSRMK2, MAPKK4, 6 Activated in response to high salt and cytotoxicity. NaCl accumulation Agrawal et al. (2002) OsMAPK5, Activated by salt accumulation Very high concentration Xiong and Yang (2003) OsMPK3, 4, 5 Activated by accumulation of arsenic stress and salts High arsenic and salt concentration Rao et al. (2010) OsMKK6 Activated in hypersensitivity of other stresses High salinity OsEDR1 Activated by high salt accumulation Excess salt amount Kim et al. (2003) OsMAPK4 Activated under salt accumulation NaCl excess amount Rao et al. (2010) Cotton GhMAPK, GhMPK2 Activated by salt stress and osmotic adjustment High amount of salts Wang et al. (2007); Zhang et al. (2011) Blue mustard CbMAPK3 Activated under salt accumulation High salt accumulation Zhang et al. (2006) Sea bean SbMAPKK Activated under salt accumulation Water reduction and salt accumulation Agarwal et al. (2010) Cucumber CsNMAPK Activated under salt accumulation Salt accumulation Xu et al. (2010) Tobacco NtSIPK Activated by salt stress and osmotic adjustment NaCl accumulation Mikolajczyk et al. (2000) Potato StMAPK3 Activated by salt stress and osmotic adjustment PEG, menthol, and NaCl treatment Zhu et al. (2020) Osmotic stress Arabidopsis AtMPK1, 4, 6, and 20 Activated under high salt accumulation and improved the osmosis Hyper-osmolarity Droillard et al. (2004); Moustafa et al. (2008) AtMKK7,9 Activated under higher NaCl concentration Sodium chloride excess Moustafa et al. (2008) AtMPK9, 17,18 Activated under higher salt accumulation Hyper-osmolarity Moustafa et al. (2014) Maize ZmMPK7 Activated under salt accumulation and molecular imbalance Hyper-osmolarity Zong et al. (2009) Tobacco NtSIPK Activated by salicylic acid under high salt concentration Higher osmotic stress Mikolajczyk et al. (2000) Alfalfa MsSIMK Upstream activation by SIMKK Higher osmolarity Jonak et al. (2004) Potato StMAPK3 Activated by NaCl (40 mM and 80 mM) Salt accumulation Zhu et al. (2020) Crops respond to salt stress through different processes like elimination and appropriation of ions (Na+ and Cl-) into vacuole to lessen cytotoxicity; research has shown that osmotic stress is also regulated by MAPKs (Kim et al., 2003). Protective proteins like late embryogenesis abundant (LEA) and chaperones, a heat shocking protein also speed up to defense the negativity of these toxic ions. MAPKs also respond by conveying signals for osmotic stress to specific effectors and play a key role to survive in the cell under high salt concentration. It is already reported that MAPK cascade is activated under salt and osmotic stress at both transcriptional and protein levels (Iftikhar et al., 2017). In A. thaliana, genes like AtMEKK1, AtMKK2, and AtMPK4, as shown in Figure 3 , have stress tolerance under salinity conditions. MMK gene named as SIMKK an upward regulator of SIMK, a MAPK gene response upregulation in alfalfa under salinity as well as osmotic stress (Xu et al., 2010). In addition, salicylic acid-induced protein kinase (SIPK) regulates osmotic stress in tobacco in a very short time (5 to 10 min) (Ghorbel et al., 2019; Habiba et al., 2021); SIPK is an Arabidopsis MPK6 homolog in tobacco. In another study, it was also shown that plant growth recovered in the overexpression lines of StMAPK3 in potato, and the lethal effects of osmotic stress and salinity were reduced by the MAPK gene family (Zhu et al., 2020). The increased content of many oxidative markers like NaCl, H2O2, polyethylene glycol (PEG), and menthol is weakened by StMAPK3 overexpression in potato (Zhu et al., 2020). Similarly, the opposite effect is shown by catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and proline content by StMAPK3. In Arabidopsis, interchangeable names MPK4 and MPK6 have been identified, whereas salinity signal responding genes like MEKK1 and MKK2 have also been recognized (Teige et al., 2004). Salt tolerance is shown by the stress marker gene MKK2 in transgenic plants. Gene promoters called RD29A and RD29B were activated by the expression of MKK and MPK, respectively (Zaheer and Akhtar, 2016), which shows that the MAPKs regulate upward under salinity and osmotic stress. Many MPKs (MPK9, MPK10, MPK11, MPK17, and MPK18), MKKs (MKK7 and MKK9), and MEKKs (MEKK3, MEKK5, MEKK6, and MEKK7) have been screened for salt and osmotic stress (Moustafa et al., 2008; Chen et al., 2015). In maize, the MAPK named ZmSIMK1 was identified as having high salt tolerance by the overexpression of Arabidopsis transgenic plants. In the same way, in maize, ZmMPK17 also showed high osmotic stress tolerance by the activation of Arabidopsis MPK17 (Yang et al., 2019), which provides an idea that further description and practical study of MPK17 and its ortholog can provide better achievement in abiotic stress tolerance gene identification and screening. It is also described that, in rice, MAPKs control salinity and osmotic stress; OsMPK4, OsMPK3, OsMSRMK2, OsEDR1, OsEDR1, OsMAPK5, and OsMAPK4 have been classsified as salinity tolerance genes (Xie et al., 2012). Salt tolerance and osmotic pressure are also affected by the activation of OsMPK5 and OsMPK4 in transgenic maize line (Xiong and Yang, 2003). Over-expressing GhMPK2 shows the osmotic stress tolerance in transgenic cotton (G. hirsutum) (Yang et al., 2019). Similarly, cucumber roots and transgenic tobacco seeds showed overexpression of MAPK genes called CsNMAPK and CsNMPAK, which showed a germination rate higher than wild type (Gomi et al., 2005), which proves that CsNMPAK performs better under salt stress condition in the early stages. Salinity is associated with osmotic stress; from the above studies, it is strongly depicted that MAPK genes that are activated under salinity conditions are also upregulated under osmotic stress conditions. The MAPK genes in different crops like Arabidposis, maize, rice, cotton, blue mustard, alfalfa, rice, tobacco, potato, sea bean, cucumber, tobacco, and potato under salinity stress and Arabidposis, maize, tobacco, alfalfa, and potato under osmotic stress are mentioned in Table 4 . The above discussion revealed that many MAPK genes related to salinity and osmotic stress had been identified, and highly expressed under saline and osmotic stress conditions. By identifying more MAPK genes in crops, crop yield and productivity can be improved, and saline soil can be brought under cultivation. 4.5 The role of MAPKs under heavy metal stress Heavy metal ions play a vital role in the development and growth as well as in the physiological processes of plants (Lee and Ellis, 2007; Raza et al., 2022e). However, at higher concentrations, they can have lethal effects on plant physiology. With the increase in concentration of heavy metals in the soil, the cellular response of the plants is activated (Raza et al., 2022e). A novel type of MAPK gene called OsMSRMK2 in rice is activated when plants have high levels of cadmium, mercury, and copper ions (Yang et al., 2019). Studies have also confirmed the activation of MAPK genes in rice (O. sativa) with the high level of cadmium ions (Haider et al., 2021). Many MAPK genes like SIMK, MMK2, MMK3, and SAMK in alfalfa (M. sativa) seedling are activated when they are exposed to copper and cadmium ions stress (Gupta et al., 2009). Studies have also confirmed that the activation of SIMKK is only under copper ion stress but not under cadmium ion stress, as shown in Table 5 . It was documented that this MAPK activity is specific in response as specific treatment indicates the specific signals' transduction (Yeh et al., 2004). Involvement of MAPK genes called OsMPK3, OsMPK4, and OsMKK4 mediated heavy metal stress tolerance in rice seedlings as shown in Figure 3 (Gupta et al., 2009). In maize (Z. mays), under heavy metal stress, the activation of MAPK genes has also been confirmed (Lumbreras et al., 2010). These findings show the role of MAPKs in signaling activation under various heavy metal stresses. Table 5 MAPK gene signaling responses in different plants under heavy metal stress conditions. Plant species MAPK genes Stress causing metals Methods Reference Alfalfa MsMMK2, MsMMK3, MsSAMK Cadmium and copper Complex activation pattern of MAPKs: SIMK, MMK2, MMK3, and SAMK Jonak et al. (2004) Rice OsMSRMK2, OsMPK3,4, and OsMKK4 Mercury, copper, cadmium, and arsenic Overexpression of functions of an OsMSRMK2 and MBP kinase Agrawal et al. (2002) OsHMA3 Cadmium Overexpression of a functional allele of OsHMA3 Ueno et al. (2010); Shao et al. (2018) OsLCT1 Cadmium Knockdown of OsLCT1 Ueno et al. (2010) OsNRAMP5 Cadmium CRISPR/Cas9-mediated editing of OsNRAMP5 Uraguchi et al. (2011) OsHMA3 Cadmium Articulation and tissue restrictions of OsHMA3 Shao et al. (2018) Maize ZmMPK3 Cadmium Signaling activation of ZmMPK3 Wang et al. (2010) From the above discussion, except rice, maize, and alfalfa, there are no other crops in which MAPK gene families have been identified. In the near future, heavy metal stress will severely threaten crops due to climate change and heavy industrialization. The researcher's job is to verify the functional roles of MAPK genes and other mechanisms to develop heavy metal resistance cultivars. 5 Conclusion There is growing evidence that the MAPK cascade is the hub of a sophisticated network structure that transduces signals related to plant stress tolerance. The MAPK cascade gradually amplifies and conveys stress signals to downstream response components through phosphorylation and dephosphorylation, leading to various stress responses. Furthermore, a better understanding of the MAPK cascades' process should make it easier to create new methods for enhancing plants' ability to withstand stress. Numerous genetic engineering methods are available to increase abiotic stress tolerance in crops. As key players in signal transduction and regulators of gene transcription, MAPK cascades have already been used to improve abiotic stress tolerance, as discussed in this review. Molecular biology analysis of the MAPK cascade's components and its function is essential for enhancing crop improvement. Research on the function of MAPK genes or the mechanism by which the MAPK cascade regulates plant stress resistance is still limited, despite many studies in plants that have demonstrated the involvement of MAPK cascades in numerous biological processes in response to abiotic and biotic stresses. In addition, different stress stimuli can activate the same MAPK cascade genes. The above discussion concludes that the MAPK cascades and the molecular mechanisms of plant stress resistance have great significance for elucidating the entire stress tolerance signal transduction pathway in plants. 6 Future perspective Abiotic stress in crops helps to expand the tolerance of crops under different abiotic stresses by various methods of genetic manipulation. A number of studies recounted that by exploiting MAPK pathways in crops like Arabidopsis and many other crops like potato, maize, rice, and poplar, stress tolerance has improved. In the near future, investigation should include detecting the MAPK substrate, and by using advanced breeding methods and molecular methodologies, the development of new lines would be able to withstand harsh environments to meet the food requirements of the increasing population. Interacting protein is the main factor that needs to identify and quantify for producing multiple environmental stress, also with their mode of action, which is like that (MAPKKK-MAPKK-MAPK) chain and accumulated into one functional 'MAPK transgenic circuits' which could be inserted into target sequence or cell through genetic engineering and biotechnology to develop a tolerance species for specific function having specific kinase protein. It is important to study the function of MAPKs related to abiotic stress in crops, and previous studies have confirmed their role in crops related to abiotic as well as biotic stress. In the future, there is a need to identify more MAPK gene families in crops related to environmental stresses and also identify their functional analysis through advanced methodologies like transcriptomics, proteomics, metabolomics, bioinformatics, CRISPR/Cas technology, and DNA/RNA sequencing to encourage analysis of a regulation network that controls abiotic stress response. In addition, identification and functional analysis of MAPKs can be further processed by mutation, gene silencing, and microRNA techniques to produce MAPK mutants and genetically engineered gene families, which transform into crops for tolerance to biotic stresses. Author contributions YM, HS, and XZ conceived the idea. YM, XZ, NZ, Nu-A, AR, and FH contributed to writing and literature search. 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PMC10000302 | PeerJ PeerJ peerj PeerJ 2167-8359 PeerJ Inc. San Diego, USA 14913 10.7717/peerj.14913 Bioinformatics Neurology RNA-seq reveals Nup62 as a potential regulator for cell division after traumatic brain injury in mice hippocampus Zhao Jianwei 12 Wang Weihua 1 Yan Ke 1 Zhao Haifeng 3 Zhang Zhen 1 Wang Yu 1 Zhu Wenyu [email protected] 1 Chen Shiwen [email protected] 2 1 Department of Neurosurgery, Suzhou Science & Technology Town Hospital, Suzhou, Jiangsu Province, China 2 Department of Neurosurgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China 3 Department of Pathology, Suzhou Science & Technology Town Hospital, Suzhou, Jiangsu Province, China Yan Yuanliang 7 3 2023 2023 11 e1491310 10 2022 25 1 2023 (c)2023 Zhao et al. 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Background Hippocampus impairment is a common condition encountered in the clinical diagnosis and treatment of traumatic brain injury (TBI). Several studies have investigated this phenomenon. However, its molecular mechanism remains unclear. Methods In this study, Illumina RNA-seq technology was used to determine the gene expression profile in mice hippocampus after TBI. We then conducted bioinformatics analysis to identify the altered gene expression signatures and mechanisms related to TBI-induced pathology in the hippocampus. Real-time quantitative polymerase chain reaction and western blot were adopted to verify the sequencing results. Results The controlled cortical impact was adopted as the TBI model. Hippocampal specimens were removed for sequencing. Bioinformatics analysis identified 27 upregulated and 17 downregulated differentially expressed genes (DEGs) in post-TBI mouse models. Potential biological functions of the genes were determined via Gene Set Enrichment Analysis (GSEA)-based Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, which suggested a series of functional changes in the nervous system. Specifically, the nucleoporin 62 (Nup62) DEG was discussed and verified. Gene ontology biological process enriched analysis suggests that the cell division was upregulated significantly. The present study may be helpful for the treatment of impaired hippocampus after TBI in the future. Traumatic brain injury RNA-seq Nup62 Bioinformatics Hippocampus The project of Shanghai Science and Technology CommissionNo. 19ZR1438600 Science and Technology Development Fund of Nanjing Medical UniversityNo. NMUB20210251 Pre-Research Fund of Suzhou Science & Technology Town HospitalNo. szkjcyy2021004 This work was supported by the project of Shanghai Science and Technology Commission (No.19ZR1438600), the Science and Technology Development Fund of Nanjing Medical University (No.NMUB20210251), and the Pre-Research Fund of Suzhou Science & Technology Town Hospital (No.szkjcyy2021004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. pmcIntroduction Temporary or permanent cognitive impairment is one of the most common complications of traumatic brain injury, mainly manifested as memory loss, poor concentration, and reduced executive ability (Maas, Stocchetti & Bullock, 2008; Paterno, Folweiler & Cohen, 2017; Sinke et al., 2021). The hippocampus is crucial to memory (Kim et al., 2015). It is a vital brain region involved in the physiological circuitry of memory and is often damaged after TBI (Graham et al., 1995). The destruction of the hippocampus is a pathological feature of the human and animal models of brain injury (Carbonell & Grady, 1999; Graham et al., 1995). TBI includes primary and secondary injuries, and the hippocampus is highly susceptible to TBI (Ansari, Roberts & Scheff, 2008). The primary brain injury is caused at the moment of the impact, which involves direct tissue damage, impaired regulation of cerebral blood flow, and diffuse axonal injury due to shearing, tearing, or stretching (Prasetyo, 2020). The secondary injury was complex and involved a cascade of ischemia, anoxia, and cytotoxic and inflammatory processes (Prasetyo, 2020). After TBI, hippocampal atrophy is a common problem in various experimental models of TBI (Bramlett & Dietrich, 2002; Saber et al., 2017) that contribute to hippocampal-dependent memory impairments. Changes were also observed in the hippocampal structure at the cellular level. Fourier transform infrared imaging (FTRI) identified TBI-caused significant structural changes with respect to total protein content, lipid content, lipid/protein ratio, and membrane lipid order (Cakmak et al., 2016; Ustaoglu et al., 2021). The dysregulation of neurotransmitters, including gamma-aminobutyric acid (GABA) and glutamate (Almeida-Suhett et al., 2015; Harris et al., 2012), led to hippocampal deficits. Also, biochemical compounds and changes in electrical neural activity affected different subsections of the rodent hippocampus following TBI (Girgis et al., 2016). As mentioned above, pathological changes occur in the hippocampus after TBI at all levels (Almeida-Suhett et al., 2015; Bramlett & Dietrich, 2002; Cakmak et al., 2016; Girgis et al., 2016; Harris et al., 2012; Saber et al., 2017; Ustaoglu et al., 2021). However, the mechanism of injury and modulation in the hippocampus post-TBI is yet controversial. Our results identified the putative genetic changes and potential therapeutic targets of hippocampal injury in mice after moderate TBI using Illumina RNA-seq technology. Strikingly, RNA sequencing technology has become a powerful research tool for exploring disease pathogenesis. In previous studies, transcriptome analyses were used to identify gene changes in the hippocampus post-TBI at later time points, such as 3 or 7 days (Attilio et al., 2021; Todd et al., 2021). As the effect of TBI on hippocampal brain tissue was time-dependent (Ustaoglu et al., 2021), in this study, 24 h post-TBI was chosen as the time point. As affected by primary and secondary injuries, the whole hippocampus tissue was examined in this research. We used a systematic approach to identify novel molecular biomarkers. In addition, the differently expressed gene (DEG) profiles were explored based on sequencing data. Functional enrichment analyses determined the hub gene-related functions. The top hub gene Nup62 was chosen, and the upregulation of Nup62 was determined by both real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) assay. These findings could provide a novel insight into TBI-induced hippocampus impairment. Materials & Methods Animals and experimental groups Male C57B6/J 8-10-weeks-old mice (20-25 g; SLAC Laboratory Animal Corporation, Shanghai, China) used in this work were bred and housed (five per cage) in standard cages under a 12-hour light-dark cycle with the controlled temperature of 23 +- 2 degC and full access to food and water. A total of 24 mice were randomly divided into two groups: TBI (n = 12) and sham-operated (n = 12). In each group, three mice as biological replicates were used for RNA sequencing, three used for (RT-qPCR), four for WB, and two for hematoxylin-eosin (HE) staining. All procedures in these studies involving animals followed the protocols approved by Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China (Approval No: 2021-B28). Samples were collected 24 h after the models were established. All mice were euthanized humanely via cervical spondylectomy. Establishment of the TBI mouse model Controlled cortical impact (CCI) was adopted as the TBI model. After the mice were anesthetized with 1% ketamine (75 mg/kg) and xylazine (10 mg/kg), their heads were fixed in a stereotaxic frame (Stoelting, Wood Dale, IL, USA), and their body temperature was kept at 37 degC placing a warming pad under the body. Then, a 10-mm-long incision was made from the midline of the skull under aseptic conditions. After separating the skin and fascia using a vascular clamp, we performed a craniotomy over the center of the right parietal bone, one mm lateral to the sagittal suture using a 4-mm trephine. Mice were excluded from the study if the dura mater was damaged during surgery. The TBI mouse model was established using a CCI device (PinPoint Precision Cortical Impactor PCI3000; Hatteras Instruments Inc., Cary, NC, USA) to simulate a moderate TBI based on our previous studies (Gong et al., 2022; Jing et al., 2020; Yuan et al., 2016). The brain injury of moderate severity was induced using CCI with the following parameters: impact velocity 1.5 m/s, dwell time 100 ms, and striking depth 1.5 mm. The bleeding was staunched with a sterile cotton compress. Bone wax was covered over the surface of the cortex, and the incision was closed carefully with interrupted 6-0 silk sutures under aseptic conditions. The sham group underwent the same procedure except for the impact injury. During the experiment, the body temperature of the mice was stabilized using a heating pad until their consciousness recovered fully; then, all mice were tagged and returned to their cages. Hippocampal extraction and mRNA sequencing The mice were anesthetized and sacrificed 24 h after TBI, and their brains were harvested immediately. The hippocampal tissues were separated from the brains according to Paxinos and Franklin's Mouse Brain Atlas (Paxinos & Franklin, 2013). The scalp of the mice was cut to expose the head after they were killed by cervical spondylectomy humanely. The mouse skull was pulled apart with tweezers. Then, the superficial cerebral cortex was carefully removed with straight forceps to expose the underlying hippocampal tissue. Similarly, the contralateral hippocampal tissue was also exposed. Finally, the hippocampus was isolated from the surrounding tissue. The brain was sectioned and stained with HE (see the photograph and HE stained section in the Supplemental Files). Total RNA was extracted using MolPure(r) Cell/Tissue Total RNA Kit (Yeasen Biotechnology (Shanghai) Co., Ltd., Shanghai, China). After generating cDNA libraries, RNA-seq was performed on the Illumina NovaSeq platform according to the manufacturer's protocol. The RNA-seq datasets have been deposited in the Gene Expression Omnibus (GEO) database under GEO: Message Body GSE214701. Bioinformatics analysis In the current analysis, FastQC ) method was adopted for quality control. HISAT2 ) was used to align the raw RNA-seq reads to the mouse reference genome (Mus musculus, GRCm38) and StringTie ) to assemble and quantify the transcripts. The DEGs between the TBI and sham groups were analyzed using the "DESeq2" R package (version 1.38) in R (version 4.2.2) statistical software (R Core Team, 2022) (settings: P < 0.05; fold-change (FC)>1.5 or <0.667; false discovery rate (FDR)<0.1). The principal component analysis (PCA) plot was used to determine the principal components using the DEGs list and visualized using the "ggbiplot" R package (version 0.55). The clustering analysis of DEGs was carried out using the "pheatmap" package (version 1.0.12) of R. The GSEA method with all genes was used for gene enrichment analysis. Functional terms were retrieved from the GO database that describes the gene attributes, including the biological process (BP), molecular function (MF), and cellular component (CC). Then, the analysis was performed to identify significantly different regulatory pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG), a major public pathway-related database. GSEA-based GO and KEGG analyses were performed using the "clusterProfiler" package (version 4.4.4; ) of R statistical software. RT-qPCR For RT-qPCR, total RNA was isolated using the MolPure(r) Cell/Tissue Total RNA Kit (Yeasen Biotechnology) and reverse transcribed into cDNA. qPCR was carried out using gene-specific primers and a-tubulin as the reference gene. Gene-specific primers used for amplification are listed in the Supplemental Files. Then, the mRNA relative expression levels were analyzed via RT-qPCR on a LightCycler 480 (Roche). Western Blot assays The isolated hippocampal tissue was homogenized in lysis buffer by ultrasonication, diluted in loading buffer (Cat# P0015; Beyotime) to estimate the protein concentration, and separated by SDS-PAGE. Subsequently, the protein was transferred to the PVDF membrane. The membranes were blocked for 1.5 h with 5% non-fat milk and probed with primary antibodies (Nup62; Proteintech, Rosemont, IL, USA, 1:10000) and a-tubulin (Proteintech, 1:15000)) overnight at 4 degC. The membrane was incubated with horseradish peroxidase (HRP)-labeled goat anti-mouse secondary antibody for one hour at room temperature, and the immunoreactive bands were visualized using Amersham Imager 680. The relative optical density was calculated by ImageJ software (NIH, USA). Statistical analysis Continuous variables were presented as means +- SD, and categorical variables were displayed as a percentage. The statistical difference between TBI and sham-operated groups was analyzed using the two-tailed unpaired t-test. GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA) was used for analyses and graphic representation of data. P-values <0.05 were considered statistically significant. Results Quality control and assembly of the raw sequence reads At 24 h after surgery, both the sham and TBI animals were sacrificed, and hippocampus samples were removed rapidly. The size of all hippocampus samples was >0.5 mg, and the 28s/18s value was >0.7 on the Illumina NovaSeq 6000 sequencer used for sequencing. A total of 53.06 million, 49.11 million, 48.80 million, 53.32 million, 40.73 million, and 44.63 million reads were obtained from Sham1, Sham2, Sham3, TBI1, TBI2, and TBI3, respectively, of which 97.63% (Sham1), 97.67% (Sham2), 97.64% (Sham3), 97.61% (TBI1), 97.40% (TBI2), and 97.55% (TBI3) were aligned to the mouse reference genome using HISAT (Table 1). After the reads were compared to the mouse genome, StringTie was used to annotate and quantify the expression (Pertea et al., 2016). Screening of DEGs The statistical power of our RNA-seq data calculated by "RNASeqpower" package was 0.8601569. A total of 44 genes were identified to be differentially expressed between TBI and sham groups using the "DESeq2" package of R; of these, 27 were upregulated and 17 were downregulated (settings: P < 0.05; fold-change (FC) < 1.5 or < 0.667; FDR < 0.1). Nup62 was the most differentially upregulated gene. Pcdhgb8 was the most differentially downregulated gene. The normalized list of all gene data is available in the Supplemental Files. A PCA plot (Fig. 1) was drawn to assess the variability of the data. The PC1 and PC2 explained 36.3% and 32.6% of the variance in the data, respectively, and the TBI group was isolated from the sham group. The top five most significantly up/downregulated DEGs between TBI and sham groups are listed in Table 2. The volcano and heat maps of all the DEGs are depicted in Fig. 2. Top five significant DEGs identified were labeled in the volcano map. Functional enrichment and pathway analyses of DEGs In our study, the GSEA method was used for gene enrichment analysis. The list of genes used in GSEA was ranked according to log2FC. Then GSEA was conducted with two gene set collections: GO and KEGG. The enrichment dot plot of GO was used to describe the BP, CC, and MF entries of all the genes between the TBI and sham groups. Figure 3 illustrates the top 10 upregulated GO terms, including "intermediate filament-based process", "keratin filament" and "keratin filament binding", the most significantly enriched GO terms belonging to BP, CC, and MF, respectively. BP refers to a series of events accomplished by one or more ordered assemblies of MFs. In this study, we focused on the BP of Nup62. Table 3 lists the top eight significantly enriched functions that Nup62 is involved in the GO term of BP. "Positive regulation of cytokinesis", "regulation of cytokinesis" and "positive regulation of centriole replication" were most significantly enriched in the BP group. After the KEGG pathway enrichment analysis, Fig. 4 shows the top 10 most enriched KEGG pathways of activated and suppressed enrichment hallmarks terms, respectively. These included "Glyoxylate and dicarboxylate metabolism", "Renin-angiotensin system", "Cytosolic DNA-sensing pathway" and "Olfactory transduction." 10.7717/peerj.14913/table-1 Table 1 Summary of sequencing and mapping results. Sample Total_mapped Unmapped Ratio Sham1 53057380 1287942 97.63% Sham2 49114576 1170052 97.67% Sham3 48798176 1179246 97.64% TBI1 53325863 1306151 97.61% TBI2 40726291 1088909 97.40% TBI3 44632092 1122300 97.55% 10.7717/peerj.14913/fig-1 Figure 1 PCA plot for all DEGs between TBI versus Sham. TBI, TBI group, marked in blue; Sham, Sham-operated group, marked in red. 10.7717/peerj.14913/table-2 Table 2 Top five most significantly up/downregulated DEGs between TBI and sham groups. Gene symbol P value Padj Status Nup62 1.49E-25 1.72E-21 Up Ldah 6.04E-11 4.64E-07 Up Klk6 1.83E-09 8.42E-06 Up Apod 3.97E-09 1.52E-05 Up Snx10 6.38E-08 0.00021 Up Pcdhgb8 9.30E-30 2.14E-25 Down Tmem70 1.05E-09 6.05E-06 Down Ptgs2 6.76E-07 0.001794 Down Alkal2 1.33E-06 0.002785 Down 6430548M08Rik 1.66E-05 0.023855 Down 10.7717/peerj.14913/fig-2 Figure 2 (A) Volcano plot of the DEGs. (B) Heatmap for all DEGs between TBI vs. sham samples. (A) Red, upregulation; blue, downregulation. (B) Red, upregulation; blue, downregulation. 10.7717/peerj.14913/fig-3 Figure 3 Top 10 most significantly enriched GSEA-based GO terms in the three functional groups (compared to the sham). MF, molecular function; CC, cellular component; BP, biological process. The intensity of the color depends on the Padj value. The size of plot depends on the gene count. 10.7717/peerj.14913/table-3 Table 3 Top eight significant functions with respect to Nup62 involved in the GO term of biological process. goID goDescription enrichmentScore P value GO:0032467 Positive regulation of cytokinesis 0.656413259 0.027891 GO:0032465 Regulation of cytokinesis 0.510884018 0.044049 GO:0046601 Positive regulation of centriole replication 0.770285358 0.078899 GO:0032954 Regulation of cytokinetic process 0.904279421 0.081439 GO:0046599 Regulation of centriole replication 0.617102394 0.095986 GO:0000910 Cytokinesis 0.392821842 0.122314 GO:0007099 Centriole replication 0.475303426 0.220104 GO:0051781 Positive regulation of cell division 0.414488468 0.247292 10.7717/peerj.14913/fig-4 Figure 4 Top 20 GSEA-based KEGG pathways. The intensity of the color depends on the Padj value. The size of plot depends on the gene count. Nup62 was increased in TBI mice Biochemical experiments verified the results (Fig. 5). The relative mRNA expression level measured by RT-qPCR showed significantly upregulated Nup62 in the TBI groups compared to the sham groups (Fig. 5A, P < 0.05). In WB assays, Nup62 also increased considerably in the TBI groups (Fig. 5B, P < 0.01). 10.7717/peerj.14913/fig-5 Figure 5 RT-qPCR and WB result in TBI mice vs. sham mice. (A) Relative mRNA expression level measured by RT-qPCR showed that Nup62 was upregulated in the TBI group. (B) WB analysis showed a significant increase in NUP62 protein expression in the TBI group. **P < 0.01, *P < 0.05. Discussion In this study, we performed a bioinformatic analysis of high-throughput sequencing to determine the gene expression profiles of mice in the hippocampus 24 h after TBI. The results showed critical roles for several genes and pathways in the hippocampus pathology after TBI. A total of 27 17 downregulated DEGs were detected in the hippocampus of TBI mice. Several pathways enriched for TBI were identified. The GO analysis demonstrated that the "intermediate filament-based process", "keratin filament" and "keratin filament binding" were the most significantly enriched GO terms containing the ranked genes belonging to BP, CC, and MF, respectively. After TBI, a series of functional changes occur in the nervous system, including "central nervous system neuron differentiation" and "nerve growth factor receptor binding". The KEGG pathway analysis revealed that "Glyoxylate and dicarboxylate metabolism" and "Cytosolic DNA-sensing pathway" were the most enriched pathways. These bioinformatics analyses may improve the understanding of hippocampal pathological processes in TBI, especially in the acute phase. According to the DEGs analysis, Nup62 levels differed significantly between the TBI and sham-operated groups. These findings were validated by RT-qPCR and WB analyses. Therefore, we were concerned about the role of Nup62 in hippocampal pathology after TBI. Nup62, located on human chromosome 19, is a component of the nuclear pore complex (NPC) and is expressed in various human tissues (Fagerberg et al., 2014). NPC is the only channel responsible for material transport in the nuclear membrane that is conserved across all eukaryotes (Huang et al., 2020). It also plays a critical role in regulating gene expression, and its abnormal function gives rise to a variety of diseases (Huang et al., 2022; Huang et al., 2020). Recent studies have investigated the fine structure of NPCs using a comprehensive technique (Allegretti et al., 2020; Beck & Hurt, 2017; Fontana et al., 2022; Tai et al., 2022). The molecular mass of vertebrate NPCs ranges from 110-125 MDa and the diameter is about 120 nm (Fontana et al., 2022). The NPCs are divided into four main rings: the cytoplasmic ring (CR) on the cytoplasmic side, the inner ring (IR) and luminal ring (LR) on the nuclear membrane plane, and the nuclear ring (NR) facing the nucleus (Fontana et al., 2022). The CR provides docking sites for cytoplasmic filaments. It consists of the Nup214 complex formed with Nup62 together with Nup214 and Nup88 (Tai et al., 2022; Wang et al., 2016; Wu et al., 2016). Nup62 plays a critical role in nuclear transportation, cell migration, and cell cycle regulation (Wu et al., 2016). A previous study showed that the neuropathology of chronic traumatic encephalopathy (CTE) patients is associated with the upregulation of the Nup62 gene (Anderson et al., 2021). Increased Nup62 in vivo and in vitro may trigger TDP-43 cytoplasmic and nuclear mislocalization, abnormalities, perinuclear accumulation, and reduced motor ability and lifespan of animals. Thus, modulating Nups, including Nup62 post-trauma, exerted a protective effect following head trauma (Anderson et al., 2021). In the chronic stress model, the altered Nup62 levels may affect the architecture and plasticity of apical dendrites in the hippocampus (Kinoshita et al., 2014). Another study reported that depletion and cytoplasmic mislocalization of Nup62 contributes to TDP-43 proteinopathy in amyotrophic lateral sclerosis (ALS)/frontotemporal lobar degeneration (FTLD) (Gleixner et al., 2022). Nup62 is also associated with other neurodegenerative diseases, such as Alzheimer's and Huntington's disease (Nag & Tripathi, 2022). In conclusion, Nup62 pathology may be a common event in various nervous system disorders. Thus, we speculated that changes in Nup62 are associated with a poor prognosis of TBI. Furthermore, our data in GO analysis suggested that altered Nup62 may cause changes in the cell cycle that lead to TBI pathology. In the GO_BP group, "positive regulation of cytokinesis", "regulation of cytokinesis", "positive regulation of centriole replication" and other cell division-related pathways were enriched post-TBI compared to the sham group. Cell division depends on the activation of the cell cycle. After TBI, cell cycle activation (CCA) occurs in the hippocampus cells, including neurons, glial cells, and progenitor cells, and contributes to secondary brain injury (Redell et al., 2020; Stoica, Byrnes & Faden, 2009). In the animal models of TBI, CCA in the brain has been well-demonstrated experimentally (Kabadi et al., 2012a; Kabadi et al., 2014; Skovira et al., 2016). Reportedly, cell cycle proteins are upregulated in post-mitotic cells, including neurons and mature oligodendrocytes, and proliferating cells, including microglia and astrocytes (Skovira et al., 2016). In the proliferating cells, CCA induced the formation of glial scar and produced the neuroinflammatory factor that ultimately led to neuronal degeneration (Kabadi et al., 2012b; Loane & Byrnes, 2010; Stoica, Byrnes & Faden, 2009). For post-mitotic cells, re-entry into the cell cycle is associated with apoptotic cell death (Skovira et al., 2016). Specifically, enhanced neurogenesis and increased proliferation of progenitor cells are observed in the hippocampus after TBI (Liu & Song, 2016). The magnitude of injury is correlated with the degree of post-TBI neurogenesis in the hippocampus (Girgis et al., 2016; Wang et al., 2016). Abnormal neurogenesis in the hippocampus may result in detrimental effects, including aberrant sprouting and migration, reduced dendritic outgrowth, and loss of newborn neurons (Gibb et al., 2015; Ibrahim et al., 2016; Robinson, Apgar & Shapiro, 2016). Taken together, CCA has an adverse impact on hippocampal function. Moreover, the cell cycle inhibitors improve the functional outcomes following TBI in several models (Kabadi et al., 2012b; Kabadi et al., 2012c; Kabadi et al., 2014). Previous studies proved that NPCs, including Nup62, regulate the gene expression at the NPC and within the nucleoplasm (Kalverda et al., 2010). Nucleoporin-chromatin interactions stimulate the cell-cycle gene expression directly inside the nucleoplasm (Casolari et al., 2004; Kalverda et al., 2010; Taddei et al., 2006). Therefore, we speculated that Nup62 affects the hippocampal function after TBI by activating the cell cycle. Nonetheless, additional in vivo and in vitro studies are required to verify this finding further. Since the present study only involves the changes in the acute phase after TBI, we observed the alteration 24 h after TBI. One limitation of the present study was the lack of experimental ethology. The experiments, such as Morris water maze and T-maze, are required to evaluate hippocampus impairment, which leads to cognitive deficits, memory difficulties, and behavioral disorders. In addition, further study is needed to address whether Nup62 dysfunction is a cause or a consequence of the hippocampus pathology in TBI to understand the exact mechanism. The correlation between the specific CCA mechanism and central nervous system damage also needs to be explored at the molecular level. Conclusions The bioinformatics analysis of DEGs showed that Nup62 mRNA was significantly upregulated in the acute stage. The biochemical experiments confirmed this conclusion at the RNA and protein levels. Post-trauma, the Nup62 protein may be upregulated at the transcriptional level. The GO_BP enrichment analysis showed that the cell division of mice after TBI treatment was significantly elevated. The data from our experiments suggest that Nup62 enhances cell division in TBI mice. Further experimental investigations on cell division after TBI should be considered. Also, the long-term effect of Nup62 after TBI needs further investigation. Supplemental Information 10.7717/peerj.14913/supp-1 Supplemental Information 1 Raw data of DEGs Click here for additional data file. 10.7717/peerj.14913/supp-2 Supplemental Information 2 Expression of NUP62 measured by WB Click here for additional data file. 10.7717/peerj.14913/supp-3 Supplemental Information 3 GSEA genes Click here for additional data file. 10.7717/peerj.14913/supp-4 Supplemental Information 4 Raw data for RT-qPCR Click here for additional data file. 10.7717/peerj.14913/supp-5 Supplemental Information 5 PCR primer Click here for additional data file. 10.7717/peerj.14913/supp-6 Supplemental Information 6 Representative photographs of whole brain and HE stained section (A) whole brains in Sham and TBI. (B) HE stained section of the TBI hippocampus. Click here for additional data file. 10.7717/peerj.14913/supp-7 Supplemental Information 7 Uncropped blots WB Click here for additional data file. 10.7717/peerj.14913/supp-8 Supplemental Information 8 ARRIVE 2.0 Checklist Click here for additional data file. We thank our colleagues, especially Qiuyuan Gong, for their valuable assistance in the experiment. Additional Information and Declarations Competing Interests Author Contributions Animal Ethics Data Availability The authors declare there are no competing interests. Jianwei Zhao conceived and designed the experiments, performed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Weihua Wang performed the experiments, prepared figures and/or tables, and approved the final draft. Ke Yan analyzed the data, prepared figures and/or tables, and approved the final draft. Haifeng Zhao performed the experiments, prepared figures and/or tables, and approved the final draft. Zhen Zhang analyzed the data, prepared figures and/or tables, and approved the final draft. Yu Wang analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Wenyu Zhu conceived and designed the experiments, authored or reviewed drafts of the article, and approved the final draft. Shiwen Chen conceived and designed the experiments, authored or reviewed drafts of the article, and approved the final draft. The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers): Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China (Approval No: 2021-B28) provided full approval for this research. The following information was supplied regarding data availability: The data is available at NCBI GEO: GSE214701. References Allegretti et al. 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PMC10000303 | PeerJ PeerJ PeerJ PeerJ 2167-8359 PeerJ Inc. San Diego, USA 15006 10.7717/peerj.15006 Biodiversity Zoology Freshwater Biology Comparative ultrastructure of the antennae and sensory hairs in six species of crayfish Kor Golara Mengal Kifayatullah Buric Milos Kozak Pavel Niksirat Hamid [email protected] Faculty of Fisheries and Protection of Waters, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice, Vodnany, Czech Republic Waiho Khor 7 3 2023 2023 11 e1500616 1 2023 14 2 2023 (c) 2023 Kor et al. 2023 Kor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Background Antennae in crayfish are essential for gaining information about the local topography and localising food, chemicals, conspecifics or predator. There are still gaps in the research on the morphology of antennae in decapods compared to other arthropods. Methodology Biometrical and ultrastructural methods were applied using light and cryo-scanning electron microscopies to study the morphology of antennae in six different crayfish species, including marbled crayfish Procambarus virginalis, Mexican dwarf crayfish Cambarellus patzcuarensis, red swamp crayfish Procambarus clarkii, signal crayfish Pacifastacus leniusculus, common yabby Cherax destructor, and spiny-cheek crayfish Faxonius limosus to find their potential morphological differences. Results Significant differences in the antenna length, length and width of each segment to carapace length ratios, and the number of segments were found in the six crayfish species. The ultrastructure revealed differences in the distribution of sensory hairs on the antenna and the morphology of the antennal surface. Conclusions The different morphology of antennae might reflect adaptation to the conditions of their specific habitats. In addition, results showed that a combination of differences in the morphological features and biometrical measurements of antennae could be used for the distinguishment of different studied crayfish species. Antenna Arthropods Biometry Electron microscopy Morphology Crustaceans Grant Agency of the University of South BohemiaGAJU 012/2022/Z and 065/2022/Z The experimental work was supported by projects of the Grant Agency of the University of South Bohemia No. GAJU 012/2022/Z and 065/2022/Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. pmcIntroduction Decapod crustaceans bear segmented sensory organs on the anterior part of their bodies called antennae (Mellon, 2012). They are well-equipped with such sensory appendages that allow them to sense chemical and hydrodynamic stimuli in their environments (Pravin et al., 2015). Such information from the antennae is used for several purposes, including detection and identification of predators, potential mates, gaining tactile information about the local topography (Basil & Sandeman, 2000; Zeil, Sandeman & Sandeman, 1985), localising food, or communicating and interacting with conspecifics (Pravin et al., 2015; Sandeman, 1985). A study of antenna morphology may also enhance our knowledge about the taxonomic and ecological status of target animals (Hao, Sun & Liu, 2020). An earlier study stated that the morphology of the setae in the antennule may reflect the phylogeny of freshwater crayfish (Hobbs, 1974). On the other hand, it can improve our understanding of the potential differences in sensory ability among different species of crayfish and provide detailed information about the selection of the proper model animal for future behavioural and toxicological studies. Crayfish are a diverse group of decapods that are distributed across the different freshwater ecosystems in the world (Breithaupt & Eger, 2002; Holdich & Lowery, 1988; Vogt, 2002). Currently, about 700 species of these animals are identified across different kinds of freshwater ecosystems, and several new species are listed each year (Crandall & De Grave, 2017). Freshwater crayfish have important ecological roles and impacts as native and invasive species in freshwater ecosystems (Patoka, Kalous & Kopecky, 2014; Patoka, Kocanova & Kalous, 2016). The antennae of other Arthropoda, such as insects, have been the subject of many morphological studies, including Diptera (Zhang et al., 2021), Lepidoptera (Limberger, Brugnera & da Fonseca, 2021), Coleoptera (Hao, Sun & Liu, 2020), Hymenoptera (Yang et al., 2021) etc., but there is scarce information regarding the fine structure of this segmented appendage in crayfish (Bender, Gnatzy & Tautz, 1984; Masters et al., 1982; Sandeman, 1985; Sandeman, 1989). Therefore, we applied light and cryo-scanning electron microscopies to investigate the biometrical and ultrastructural features of the antennae from six crayfish species inhabiting different habitats, including marbled crayfish Procambarus virginalis, Mexican dwarf crayfish Cambarellus patzcuarensis, red swamp crayfish Procambarus clarkii, spiny-cheek crayfish Faxonius limosus (Cambaridae), signal crayfish Pacifastacus leniusculus (Astacidae) and common yabby Cherax destructor (Parastacidae) to find the potential morphological differences among species. Materials and Methods Animals All protocols and ethics for animal handling were approved by the national laws and regulations on animal welfare 246/1992, and the institutional animal care guidelines of the Faculty of Fisheries and Protection of Waters of the University of South Bohemia in Ceske Budejovice. All efforts were made to reduce animal suffering. It should be noted that no animals were killed during our study. Marbled crayfish (19.7 +- 0.3 mm, n = 10), red swamp crayfish (41.2 +- 1.8 mm, n = 10), spiny-cheek crayfish (24.5 +- 1.7 mm, n = 8), and common yabby (27.1 +- 1.6 mm, n = 6), crayfish were obtained from the experimental culture of the Laboratory of freshwater ecosystems, Faculty of fisheries and protection of waters, Vodnany, Czech Republic. Mexican dwarf crayfish (8.5 +- 0.2 mm, n = 10) were purchased from the pet shop. Signal crayfish (42.7 +- 0.7 mm, n = 10) were caught from Kresanovsky creek near Vimperk, Czech Republic. Crayfish were separately acclimatised in plastic boxes with 1 L of aerated aged tap water before the experiment. Prior to sampling, the animals were anaesthetised on ice for 10 min. Antenna samples were collected equally from both sexes of adult crayfish using scissors and used for biometrical and ultrastructural purposes. Biometrical measurements Intact animals without injuries were used for the experiment. The light microscope (Olympus SZX16; Olympus, Shinjuku City, Japan) equipped with a DP74 camera was applied. The carapace length, antenna length, length and width of each antennal segment were measured by ImageJ (NIH, Bethesda, MD, USA). Antenna total length, width and lengths of each antennal segment in the different species were adjusted by dividing into the carapace length to remove differences among the size of animals (Weiss, Thatje & Heilmayer, 2010). For statistical analysis, Kolmogorov-Smirnov and Levene's tests were used for the normality and homogeneity of variance using Statistica 13 software (StatSoft, Inc., Tulsa, OK, USA). For normal data (antenna to carapace length ratio), the one-way analysis of variance (ANOVA) with subsequent Tukey's post-hoc test was carried out to evaluate differences among species. The length and width of each segment to carapace ratios, and number of segments were not normally distributed and assessed using the non-parametric Kruskal-Wallis test with subsequent multiple comparisons post-hoc statistical analysis. For all statistical tests, p < 0.05 was considered significant. Data are expressed as the mean +- SEM. Electron microscopy Scanning electron microscopy (SEM) JEOL 7401F (JEOL Ltd., Akishima, Japan) equipped with a cryo-attachment CryoALTO 2500 (Gatan, Inc., Pleasanton, CA, USA) was used to study the antennal ultrastructure and sensory hairs. The samples were placed on the stub using double copper tape and Tissue-Tek. The samples were frozen by plunging into a liquid nitrogen slush. After freezing, the samples were transferred to the high vacuum cryo-preparation chamber, where the surface of the samples were sublimated at a temperature of -98 degC for 2 min. After sublimation, the samples were coated with 5 nm of gold at -135 degC. The coated samples were inserted into the Field Emission Electron Microscope (JSM-7401-F; JEOL Ltd., Akishima, Japan) precooled at -135 degC. Images were obtained using an Everhart-Thornley detector at an accelerating voltage of 1.5 kV using Gentle Beam (GB) low mode (Niksirat, Kouba & Kozak, 2015). Results Biometrical measurements Our results showed a significant (p = 0.0005, df = 5) difference in the antenna to carapace length ratio among our studied species. While common yabby showed the longest antenna to carapace length ratio, the signal and Mexican dwarf crayfish had the lowest values of this ratio (Fig. 1). 10.7717/peerj.15006/fig-1 Figure 1 Comparison of antenna to carapace length ratio among six species of freshwater crayfish, including marbled crayfish Procambarus virginalis, Mexican dwarf crayfish Cambarellus patzcuarensis, red swamp crayfish Procambarus clarkii, signal crayfish Pacifastacus leniusculus, common yabby Cherax destructor, and spiny-cheek crayfish Faxonius limosus. Letters indicate significant differences between species. The results showed a significant (p = 0.0001, df = 5) difference among the number of segments of the antennae in different species. While common yabby showed the highest number of segments, the Mexican dwarf and spiny-cheek crayfish had the lowest number of segments (Fig. 2). 10.7717/peerj.15006/fig-2 Figure 2 Comparison of the number of segments in the antenna of six freshwater crayfish species including marbled crayfish Procambarus virginalis, Mexican dwarf crayfish Cambarellus patzcuarensis, red swamp crayfish Procambarus clarkii, signal crayfish Pacifastacus leniusculus, common yabby Cherax destructor, and spiny-cheek crayfish Faxonius limosus. Letters indicate significant differences between species. The results indicated a significant (p = 0.0001, df = 5) difference among the lengths of each antenna segment to carapace length ratio in the different species. The longest and shortest lengths of the lower, middle and upper parts of each antenna segment were recorded in Mexican dwarf and red swamp crayfish, respectively (Table 1). 10.7717/peerj.15006/table-1 Table 1 Comparison of different length of each antenna segment/carapace length ratio in the different species of freshwater crayfish. Spiny cheek Dwarf Signal Red swamp Marbled Yabby Upper a(B) 0.0095 +- 0.0002 b(B) 0.0167 +- 0.0003 c(B) 0.0125 +- 0.0002 d(C) 0.0068 +- 0.0001 a(C) 0.0102 +- 0.0001 a(B) 0.0098 +- 0.0002 Middle a(A) 0.0106 +- 0.0002 b(AB) 0.0170 +- 0.0003 b(A) 0.0145 +- 0.0001 c(B) 0.0076 +- 0.0001 a(B) 0.0109 +- 0.0001 a(B) 0.0097 +- 0.0001 Lower a(A) 0.0121 +- 0.0001 b(A) 0.0174 +- 0.0003 c(A) 0.0138 +- 0.0002 d(A) 0.0081 +- 0.0001 a(A) 0.0119 +- 0.0001 d(A) 0.0085 +- 0.0001 Total a 0.0105 +- 0.0001 b 0.0170 +- 0.0001 c 0.0136 +- 0.0001 d 0.0075 +- 0.00006 a 0.0110 +- 0.0001 e 0.094 +- 0.0001 Note: Within columns and rows, values marked with different capital and small letters indicate significant differences, respectively. Our results showed a significant (p = 0.0001, df = 5) difference among the widths of each antenna segment to carapace length ratio in the studied species. The width of each segment for all species decreased from the lower to the upper parts of the antenna. For the different parts of the antenna, the widest and narrowest were recorded in Mexican dwarf and marbled crayfish in the upper part, common yabby and marbled crayfish in the middle part, and signal and Mexican dwarf crayfish in the lower part, respectively (Table 2). 10.7717/peerj.15006/table-2 Table 2 Comparison of different width of each antenna segment/carapace length ratio in the different species of freshwater crayfish. Spiny cheek Dwarf Signal Red swamp Marbled Yabby Upper a(C) 0.0081 +- 0.0001 a(C) 0.0091 +- 0.0007 bc(C) 0.0079 +- 0.0001 ac(C) 0.0074 +- 0.0001 b(C) 0.0065 +- 0.0001 a(C) 0.0083 +- 0.0002 Middle ab(B) 0.0126 +- 0.0002 b(B) 0.0134 +- 0.0002 c(B) 0.0156 +- 0.0002 c(B) 0.0148 +- 0.0001 a(B) 0.0124 +- 0.0001 d(B) 0.0169 +- 0.0002 Lower a(A) 0.0219 +- 0.0003 a(A) 0.0208 +- 0.0002 b(A) 0.0266 +- 0.0002 a(A) 0.0221 +- 0.0002 a(A) 0.0229 +- 0.0003 b(A) 0.0260 +- 0.0003 Total a 0.0144 +- 0.0003 ab 0.0148 +- 0.0003 b-e 0.0164 +- 0.0003 ae 0.0148 +- 0.0003 a 0.0140 +- 0.0003 d 0.0171 +- 0.0003 Note: Within columns and rows, values marked with different capital and small letters indicate significant differences, respectively. Ultrastructural features The scanning electron microscope micrographs showed a general conserved pattern, including segmented organs carrying two forms of sensory hairs on the surface in studied crayfish species (Figs. 3-9). Sensory hairs emerged from the upper part of each segment and extended upwards. While some of the sensory hairs are tubular or cone-shaped (non-branched), the second form consists of feather-like branches which are originated from the main shaft. In addition, there are differences in the ultrastructure of the antenna surface among the studied species (Figs. 3-9). 10.7717/peerj.15006/fig-3 Figure 3 A general view of the morphology of antennae in six species of crayfish. 10.7717/peerj.15006/fig-4 Figure 4 (A) An overview of antenna in signal crayfish (Pacifastacus leniusculus), (B) a higher magnification of two forms of sensory hairs (I, non-branched; II, branched), (C) a higher magnification of squamous surface of antenna. 10.7717/peerj.15006/fig-5 Figure 5 (A) An overview of antenna in Mexican dwarf crayfish (Cambarellus patzcuarensis), (B) a higher magnification of two forms of sensory hair (I, non-branched; II, branched), and (C) a higher magnification of wavy and wrinkled surface of antenna. 10.7717/peerj.15006/fig-6 Figure 6 (A) An overview of antenna in marbled crayfish (Procambarus virginalis), (B) a higher magnification of two forms of sensory hair (I, branched; II, non-branched), (B and C) a higher magnification of relatively squamous surface of antenna. 10.7717/peerj.15006/fig-7 Figure 7 (A) An overview of antenna in red swamp crayfish (Procambarus clarkii), (B) a higher magnification of two forms of sensory hair (I, non-branched; II, branched), and (C) a higher magnification of relatively smooth surface of antenna. 10.7717/peerj.15006/fig-8 Figure 8 (A) An overview of antenna in spiny-cheek crayfish (Faxonius limosus), (B) a higher magnification of two forms of sensory hair (I, non-branched; II, branched), and (C) a higher magnification of relatively squamous surface of antenna. 10.7717/peerj.15006/fig-9 Figure 9 (A) An overview of antenna in common yabby (Cherax destructor), (B) a higher magnification of two forms of sensory hair (I, non-branched; II, branched), and (C) a higher magnification of tuberculous surface of antenna. Mostly sparse and short sensory hairs were observed in the antenna of signal crayfish, and the branched form of sensory hair was sparsely distributed. The surface of the antenna in signal crayfish was squamous (Figs. 4A-4C). In Mexican dwarf crayfish, we observed mostly the non-branched form of sensory hairs and rarely the branched form. In most cases, the sensory hairs were as long as the length of the next segment. The surface of the antenna in this species is relatively wavy and wrinkled (Figs. 5A-5C). In marbled crayfish, we observed short and sparse sensory hairs of both forms. The sensory hairs were not frequent and relatively short, and the surface of the antenna is relatively squamous (Figs. 6A-6C). In red swamp crayfish, both forms of branched and non-branched sensory hairs were visible. They extended distally as far as the middle of the next segment, and the surface of the antenna in this species was relatively smooth (Figs. 7A-7C). Our observations in spiny-cheek crayfish showed that most of the sensory hairs in this species are branched. The surface of the antenna is relatively squamous (Figs. 8A-8C). In common yabby, we observed that the frequency of hairs in each segment is higher, and they consist primarily of the long, branched form. The surface of the antenna in this species is not smooth and covered by tubercles. The density of sensory hair is high, and the length of them is extended into half to whole length of an antennal segment (Figs. 9A-9C). Discussion In the present study, we have demonstrated a comparative morphology of the antennae and accompanied sensory hairs among different freshwater crayfish species. The results of our study showed a general conserved pattern of morphology in antennae and their sensory hairs for all studied species. Two forms of sensory hairs were observed on the crayfish antennae, including branched and non-branched types. Similar forms of sensory hairs are supported by the literature. Two morphologically different forms of sensory hairs were detected on the antennae and antennules of narrow-clawed crayfish Pontastacus leptodactylus including smooth and feathered sensory hairs. It was shown that while smooth hairs react against the surrounding environment movement and touching, feathered hairs response to direct touch and displacement of main shaft by bending (Bender, Gnatzy & Tautz, 1984; Tautz et al., 1981). It was reported that feathered hairs are innervated by two sensory cells, while smooth hairs could have more than two sensory cells (Tautz et al., 1981). Contrary, it was observed that the feathered hairs in narrow-clawed crayfish (Bender, Gnatzy & Tautz, 1984) and common yabby (Sandeman, 1989) are not innervated and are more likely to serve as structural support for the long and flexible antennae. Also, two forms of beaked and feathered sensory hairs in red swamp crayfish were reported (Mellon, 2012), which are morphologically similar to non-branched and branched hairs in our study. It is possible that these two forms of sensory hairs have two different functions including mechanoreceptors (Kouyama & Shimozawa, 1982) or chemoreceptors (Fedotov, 2009). On the other hand, these could be different developmental stages of a sensory hair. The emergence of a sensory hair from the pore on the surface of the antenna could be facilitated when it is non-branched and then branches appear to increase the surface and sensitivity of sensory hairs to stimuli. Similar morphology of sensory hairs that were observed on antenna, antennule (Tautz et al., 1981), chelae (Belanger et al., 2008) and maxillipeds (Patoka, Blaha & Kouba, 2017) of crayfish may indicate that these animals use similar sensory appendages with equivalented functions across their bodies. Antennae and sensory hairs morphology vary among species that may reflect adaptation for necessary mechanosensory and chemosensory requirements in the specific environment (Hallberg, Johansson & Wallen, 1997; Tierney, Thompson & Dunham, 1986). For example, it was stated that surface-dwelling species have a significantly higher density of sensory hairs on their sensory organ compared to cave-dwelling crayfish species, while cave-dwelling species possess longer individual sensory hairs (Ziemba et al., 2003). Also, two cave (troglobitic) crayfish species with well-developed hairs in their maxillipeds, namely Troglocambarus maclanei and Cherax acherontis probably use their dense setose maxillipeds to collect organic material from the water current as a food source (Patoka, Blaha & Kouba, 2017). In addition, it was shown that different water flow in habitats such as lake, creek, river or hatchery conditions could cause differences in morphological features of sensory hairs in virile crayfish Faxonius virilis (Mead, 2008). Hence, the differences observed in the morphology of sensory hairs among different crayfish species could be caused by different levels of stimuli that they encounter in their specific habitat based on biodiversity, water quality, food availability, the intensity of interspecific interactions and density of predators. But it is unknown if the differences are evolved by short-term exposures during an individual's lifetime or by long-term existence in specific habitats/conditions after several generations. Common yabby inhabits dark and turbid waters. Therefore, their tactile senses are a great source of information about their environment that highlights the importance of the antennae and sensory hairs in the common yabby (Basil & Sandeman, 2000). The antennae in common yabby can sense environmental stimuli in the absence of the eye, which is necessary for a dark environment (Varju, 1989). It could be a reason for their higher density of sensory hairs compared to the other studied species. Also, it could be speculated that tropical species such as common yabby crayfish, which live at sites with higher biodiversity, encounter lots of stimuli and therefore need higher density of sensory hairs. We speculate that species such as signal crayfish that inhabit colder waters with lower biodiversity develop shorter and less dense complements of sensory hairs. However, there is one exception such as koura crayfish from New Zealand where temperature falls down below 10 degC within the year, and this crayfish is covered by dense hairs (Hopkins, 1967). As a result, different habitats may expose the animals to varying levels of stimuli from the prey, predator, and conspecific, and animals may have to adapt themselves to the environment by changing the morphology and intensity of the sensory hairs, which allows them to fit better in their related environments. It will be promising to compare cultured and wild animals, as well as animals from different localities with different conditions to set up clear explanations for the drivers of the different shapes and densities of crayfish hairs. Even if we do not know the hidden drivers, we can say that the distribution and quantity of sensory hairs with various functions may have a significant impact on how surrounding information is received and can therefore affect the final response as described in other arthropods such as insects (Dong et al., 2020). It would be interesting to study wild living and cultured animals and the potential differences in the morphology of sensory hairs. The next questions should be then asked about the level of the ability of each species to detect stimuli in the environment in accordance with their density of sensory hairs and morphology. A comparative study showing how different crayfish species react in front of similar stimuli can also help to find a suitable model organism for behavioural and toxicological studies. Conclusions Despite the similar general morphology in the antennae and sensory hairs, there are differences in ultrastructural and biometrical traits that may help in the distinguishment of the studied crayfish species. Two forms of sensory hairs can reflect different functions or different developmental stages of these appendages. The different morphology of antennae might reflect adaptation to the conditions of their specific habitats. Different morphology and density of sensory hairs could also be a mark of different levels of sensitivity to detect chemicals, prey, predators, conspecifics and other stimuli in their environments. Further studies are needed to compare the sensitivity of different crayfish species to the stimuli based on their different sensory hairs density and morphology to find the best model species candidate for the behavioural and toxicological studies. Supplemental Information 10.7717/peerj.15006/supp-1 Supplemental Information 1 Data. Click here for additional data file. We are thankful for the technical support from the Laboratory of Electron microscopy facility in the Biology Centre (CAS) in Ceske Budejovice. Additional Information and Declarations Competing Interests Author Contributions Ethics Data Availability The authors declare that they have no competing interests. Golara Kor conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Kifayatullah Mengal performed the experiments, authored or reviewed drafts of the article, and approved the final draft. Milos Buric analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Pavel Kozak analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Hamid Niksirat conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers): All protocols and ethics for animal handling were approved by the national laws and regulations on animal welfare 246/1992, and the institutional animal care guidelines of the Faculty of Fisheries and Protection of Waters of the University of South Bohemia in Ceske Budejovice. The following information was supplied regarding data availability: The raw data is available in the Supplemental File. References Basil & Sandeman (2000) Basil J Sandeman D Crayfish (Cherax destructor) use tactile cues to detect and learn topographical changes in their environment Ethology 2000 106 247 259 10.1046/j.1439-0310.2000.00524.x Belanger et al. 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PMC10000304 | PeerJ PeerJ peerj PeerJ 2167-8359 PeerJ Inc. San Diego, USA 14866 10.7717/peerj.14866 Agricultural Science Genetics Plant Science Quantitative trait loci associated with straighthead-resistance used for marker assisted selection in rice (Oryza sativa L.) RIL populations Pan Xuhao [email protected] 12 Li Yiting 1 Li Xiaobai 3 1 Tobacco Research Insistitute of Chinese Academy of Agriculture Sciences, Qingdao, China 2 Rice Institute, Sichuan Agriculture University, Chengdu, China 3 Zhejiang Academy of Agricultural Sciences, Zhejiang, China Lal Mohan 7 3 2023 2023 11 e148669 8 2022 17 1 2023 (c)2023 Pan et al. 2023 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Straighthead is a physiological disorder of rice (Oryza sativa L.) that causes dramatic yield loss in susceptible cultivars. This disorder is found worldwide and is reported to increasingly occur in the southern United States. Genetic resistance breeding has been considered as one of the most efficient methods for straighthead prevention because the traditional prevention method wastes water and costs labor. In this study, we analyzed the genetic effects of five straighthead quantitative trait loci (QTLs), namely, AP3858-1 (qSH-8), RM225 (qSH-6), RM2 (qSH-7), RM206 (qSH-11), and RM282 (qSH-3), on the recombinant inbred lines (RILs) developed from Jing185/Cocodrie and Zhe733/R312 populations using our five previously identified markers linked to these QTLs. As a result, recombinant inbred lines (RILs) with four resistant alleles at the four loci (AP3858-1, RM225, RM2, and RM206) exhibited the highest straighthead resistance. This result suggests that the four markers could be efficiently used to select the straighthead-resistant recombinant inbred lines (RILs). Furthermore, by using AP3858-1, we successfully obtained five straighthead-resistant recombinant inbred lines (RILs) with more than 50% genetic similarity to Cocodrie. These markers and recombinant inbred lines (RILs) can be used for future straighthead resistance breeding through marker-assisted selection. Straighthead Resistant breeding QTLs Gene effect Oryza sativa L. Marker-assisted selection The authors received no funding for this work. pmcIntroduction Straighthead is a physiological disorder of rice that is characterized by sterile florets and distorted spikelets (Yan et al., 2005). It can make rice kernels empty and panicles erect and fail to head out. As a result, straighthead often causes dramatic yield loss in susceptible cultivars (Dilday et al., 2000). Straighthead was first reported in the US (Wells & Gilmour, 1977) and is now found in Japan (Takeoka, Tsutsui & Matsuo, 1990), Australia (Dunn et al., 2006), Portugal (Cunha & Baptista, 1958), Thailand (Weerapat, 1979), and Argentina (Yan et al., 2010). It has become a huge threat to rice production in the southern US and worldwide. According to previous studies, straighthead can be caused by numerous factors, such as sandy to silt loam-textured soils (Ehasanullah & Meetu, 2018), low free iron and low pH in soil (Hua et al., 2011; Huang et al., 1997), presence of As, Mn, Ca, and S, and soil organic matter (Hua et al., 2011; Hulbert & Bennetzen, 1991). In the southern U.S., arsenic-based herbicides such as monosodium methanearsonate (MSMA) have been widely applied in cotton-growing areas. Thus, arsenic (As) usually residues in paddies. Toxicity in rice induces a series of symptoms, such as decreases in plant height and tillers (Kang et al., 1996), reduction in shoot and root growth (Dasgupta et al., 2004; Rahman et al., 2012), inhibition of seed germination (Shri et al., 2009; Rahman et al., 2012), decline in chlorophyll content and photosynthesis, and sometimes plant death (Rahman et al., 2007). Notably, As can cause typical straighthead symptoms in susceptible rice cultivars in MSMA-applied soil (Rahman et al., 2008; Lomax et al., 2012). Thus, MSMA-induced application is a common method of evaluating rice straighthead (Slaton et al., 2000; Wilson Jr et al., 2001). For straighthead prevention, one method used is water management called "draining and drying" (D&D). In this method, farmers need to drain their rice field about two weeks after a permanent flood and then wait for reflooding until the rice leaves exhibit drought stress symptoms (Rasamivelona, Kenneth & Robert, 1995; Slaton et al., 2000). In Arkansas, one-third of the rice fields applies the D&D method, which results in approximately 150 million m3 of wasted irrigation water every year (Wilson Jr & Runsick, 2008). Clearly, the method costs natural resources and manpower and also leads to drought-related yield loss. Resistant breeding is considered as the most efficient and environmentally friendly strategy for straighthead prevention. A number of resistant germplasms have been identified, and the genetic base of straighthead has been examined (Yan et al., 2002; Pan et al., 2012). Marker-assisted selection (MAS) has been used in resistant breeding for many years and has been demonstrated as a feasible strategy in multiple crops (Yan et al., 2005). In our previous study (Pan et al., 2012), we constructed two recombinant inbred line (RIL) F9 populations using two resistant parents (Zhe733 and Jing185) and the susceptible parents Cocodrie and R312. Five quantitative trait loci (QTLs), namely, qSH-3, qSH-6, qSH-7, qSH-8, and qSH-11, were identified to be associated with straighthead via linkage mapping using the two RIL populations. Four QTLs (qSH-6, qSH-7, qSH-8, and qSH-11) were determined for the Zhe733/R312 population and two QTLs (qSH-3 and qSH-8) were identified for the Cocodrie/Jing185 population. Of these QTLs, qSH-8,which is 290 kb long and is found on chromosome 8, was identified in the two populations. Moreover, the presence of qSH-8 was confirmed in the F2 and F2:3 populations of Zhe733/R312 (Li et al., 2016b). Therefore, qSH-8 was proven as a major QTL for straighthead resistance. Furthermore, five markers, namely, RM282, RM225, RM2, AP3858-1, and RM206 (Table S1), were associated with the five aforementioned QTLs, respectively. Arkansas accounts for a large part of rice production in the U.S.. However, as previously mentioned, many cultivars grown in this region are highly susceptible to straighthead. For instance, Cocodrie, a major cultivar grown in Arkansas, lost up to 94% of its yield when straighthead occurred (Linscombe et al., 2000; Wilson Jr et al., 2001). Thus, genetically improving straighthead resistance is necessary to ensure high rice yields. In the present study, our objective is to identify RILs with straighthead-resistant QTLs and similar agronomic traits and backgrounds to Cocodrie in the Cocodrie/Jing185 population for use in further resistant breeding. Materials & Methods Plant material Two RIL F9 populations, Zhe733/R312 and Cocodrie/Jing185, were previously developed and evaluated for straighthead (Fig. 1) (Pan et al., 2012). Resistant cultivars Zhe733 (PI 629016) and Jing185 (PI 615205) and susceptible cultivar R312 (PI 614959) were from China. Cocodrie (PI 606331), another susceptible cultivar, is widely grown in the US. All three cultivars from China belong to indica, whereas Cocodrie belongs to japonica. A total of 170 F9 RILs were identified in the Zhe733/R312 population, whereas 91 F9 RILs were produced in the Cocodrie/Jing185 population. Phenotyping Both Zhe733/R312 and Cocodrie/Jing185 populations were planted in MSMA-treated soil at Dale Bumpers National Rice Research Center near Stuttgart, Arkansas for two years (2010 and 2011). Using a randomized complete block design, the RILs of the two F9 populations were planted in single-row field plots (0.62 m2) with three replications, as previously described (Pan et al., 2012). Exactly 6.7 kg ha-1 of MSMA was applied to the soil surface and incorporated prior to planting, as previously described (Yan et al., 2005). The four parents (Zhe733, R312, Cocodrie, and Jing185) were repeatedly planted in each field tier of 99 rows as controls. Field management was performed as previously described (Yan et al., 2008). Evaluation of straighthead rating was based on floret sterility and panicle development using a scale of 1 to 9 at the maturity stage (Yan et al., 2005). A score of 1 represented normal plants with panicles fully emerged and more than 80% grains developed, whereas 9 represented sterile plants with no panicle emergence and complete absence of developed grains. Based on our previous research, RILs with a score of 4.0 or below were resistant and had 41%-60% seed sets or higher, whereas RILs with a score of 6.0 or above were susceptible and had 11%-20% seed sets or lower (Li et al., 2016b). The Cocodrie/Jing185 population was then planted in clean soil without MSMA at Dale Bumpers National Rice Research Center near Stuttgart, Arkansas for two years (2010 and 2011). To ensure a reliable evaluation, we performed water management to prevent straighthead. We conducted a randomized complete block design for the field experiments. RILs were planted in single-row field plots (0.62 m2) with three replications each year. The parents were repeatedly planted in a field tier of 99 rows as controls. Evaluations of the heading date, height, and tillers were conducted in the field. The heading date for each plot was recorded when 50% of the panicles had emerged from the rice culms, as determined using visual estimation. The height and tillers of each plot were assessed at the mature stage using three central individuals, and the plant height was measured from the ground to the tip of the rice panicle (Counce, Keisling & Mitchell, 2000). The three central individuals of each plot were then harvested and air-dried in a greenhouse for biomass evaluation. Genotyping and genetic analysis DNA was extracted from each RIL of the two populations and their parents following the CTAB method described by Hulbert & Bennetzen (1991). The straighthead-linked markers, namely, RM282, RM225, RM2, AP3858-1, and RM206, were used to screen the RILs of the two populations. DNA amplification was performed as previously described (Pan et al., 2012). As to genotyping, alleles corresponding to resistant or susceptible parents were noted as "a" or "b," respectively. RILs with both alleles were noted as "h." Missing data were noted as ".". According to our previous report, "a" was a resistant allele and "b" was susceptible at each QTL locus of the ZHE733/R312 population. In the Cocodrie/Jing185 population, "a" was notably resistant and "b" was the susceptible allele at the qSH-8 locus, whereas "a" was the susceptible allele and "b" was the resistant allele at the qSH-3 locus. RILs with straighthead ratings <= 4.0 were selected for further allelic analysis using a number of markers. These markers, including RM225, RM2, RM206, RM282, and AP3858-1, were associated with straighthead resistance (Pan et al., 2012) and can be useful in MAS. Identification of RILs and statistical analysis In the Cocodrie/Jing185 population, RILs with over 50% Cocodrie genetic background were selected for further analysis. The agronomic traits of these selected RILs were analyzed using analysis of variance (ANOVA). Duncan's multiple range test was performed between selected RILs and Cocodrie based on the agronomic traits. RILs with different allele combinations were compared with RILs without any resistant alleles (RWARA) using the F-test and T-test. All these statistical procedures were conducted using SAS software v9.1 (SAS Institute Inc., Cary, NC, USA). Results Gene effect of straighthead-related QTLs Four SSR markers linked to straighthead-resistant QTLs, namely, RM225 (qSH-6), RM2 (qSH-7), RM206 (qSH-11), and AP3858-1 (qSH-8), were identified in the Zhe733/Jing185 population in a previous study (Pan et al., 2012). Of these QTLs, 5 RILs with different genotypes were compared based on straighthead rating, with the two parents (susceptible parent R312, which had a straighthead rating of 8.8, and resistant parent R312, which had a straighthead rating of 1.2) set as controls. The results (Fig. 2A) show that ZR-64, which had susceptible alleles at the four loci, had the highest straighthead rating (8.7). By contrast, the other four RILs (ZR-238, ZR-132, ZR-14, and ZR-83), which have at least one resistant allele each, showed lower straighthead ratings than other RILs which have none. In particular, ZR-83, which has four resistant alleles, had the lowest straighthead rating (1.3). 10.7717/peerj.14866/fig-1 Figure 1 Straighthead phenotype of parents, Cocodire (susceptible)/Jing185 (resistant) and Zhe733 (resistant)/R312 (susceptible). 10.7717/peerj.14866/fig-2 Figure 2 Straighthead rating of RILs with different genotype in Zhe733/R312 population (A) and Cocodrie/Jing185 population (B). SSR markers RM282, RM225, RM2, AP3858-1 and RM206 were previously identified to associated with five straighthead resistant QTLs qSH-3, qSH-6, qSH-7, qSH-8 and qSH-11, respectively. Black bar represents resistant allele, white bar represents susceptible allele in MASA-induced field. S: susceptible. R: resistant. Two SSRs linked to the straighthead-related QTLs RM282 (qSH-3, susceptible QTL) and AP3858-1 (qSH-8, resistant QTL) were identified in the Cocodrie/Jing185 population in a previous study (Pan et al., 2012). Four RILs were selected for comparison based on the straighthead ratings. The two parents (the susceptible parent "Cocodrie" with a straighthead rating of 9.3 and the resistant parent "Jing185" with a straighthead rating of 2.2) were set as controls. The results (Fig. 2B) show that RIL CJ-405, which has no resistant alleles at both loci, showed a very high straighthead rating of 9.0. CJ-522, with one resistant allele at RM282, showed a straighthead rating of 7.2. CJ-407, which has resistant alleles only at AP3858-1, showed a straighthead rating of 2.7. Furthermore, CJ-427, which has both resistant alleles, showed a straighthead rating of 1.8. Clearly, qSH-8 showed the highest contribution to resistance. Therefore, the RILs CJ-407 and CJ-427, which have the major resistant QTL, can be used as elite lines for future straighthead-resistance breeding programs. Allelic analysis of straighthead-related QTLs in Zhe733/R312 and Cocodrie/Jing185 populations To investigate the effects of the five straighthead-related QTLs, 147 RILs from Zhe733/R312 (Table S2) and 91 RILs (Table S3) from Cocodrie/R312 were used in this study. In the Zhe733/R312 population (Fig. 3A and Table 1), 16 RILs without any resistant allele (RWARA-ZR) exhibited a mean straighthead rating of 8.66. Six RILs with the resistant allele qSH-6 (RM225) exhibited a mean straighthead rating of 8.18. Similarly, RILs with the resistant alleles qSH-7 (RM2) and qSH-11 (RM206) showed mean straighthead ratings of 8.55 and 8.29, respectively. Eight RILs with resistant alleles at the three loci (qSH-6 *qSH-7 *qSH-11) exhibited a much lower mean straighthead rating of 3.0. Seven RILs with the resistant allele qSH-8 (AP3858-1) showed a mean straighthead rating of 5.24. Moreover, RILs containing combinations of qSH-8 (AP3858-1) and any of the other three loci showed mean straighthead ratings of 5.80 (qSH-11 *qSH-8), 4.88 (qSH-6 *qSH-8), and 4.45 (qSH-7 *qSH-8). RILs with the three resistant alleles showed mean straighthead ratings of 2.84 (qSH-6*qSH-7*qSH-11), 1.75 (qSH-6*qSH-7*qSH-8), 2.11 (qSH-6*qSH-11*qSH-8), and 1.95 (qSH-7*qSH-11*qSH-8). The lowest straighthead rating (1.64) was identified in the five RILs with resistant alleles at all four loci (qSH-6 *qSH-7 *qSH-11 *qSH-8). Significant differences were found between all resistant RILs and RWARA-ZR, whereas no significant differences were observed between all susceptible RILs and RWARA-ZR (Fig. 3A). 10.7717/peerj.14866/fig-3 Figure 3 Straighthead rating of RILs with different genotype in MASA-induced Zhe733/R312 population (A) and Cocodrie/Jing185 population (B). Green bar represents susceptible phenotype with straighthead rating above 6, blue bar represents medium phenotype with straighthead rating between 6 and 4, red bar represents resistant phenotype with straighthead rating blow 4. RWARA-ZR: RILs without any resistant allele in Zhe733/R312 population. RWARA-CJ: RILs without any resistant allele in Cocodrie/Jing185 population. ns: indicates not significant (p > 0.05). **: represents RILs significantly different from RWARA-ZR or RWARA-CJ at the 0.01 probability level in each population, respectively. 10.7717/peerj.14866/table-1 Table 1 Genetic analysis of straighthead-associated QTLs in MASA-induced Zhe733/R312 population. QTLs Genotype 1 No. of RILs Straighthead rating 2 RWARA-ZR b*b*b*b 16 8,66 +- 0.35 qSH-6 a 6 8.18 +- 0.65 qSH-7 a 13 8.55 +- 0.35 qSH-11 a 10 8.29 +- 0.45 qSH-8 a 7 5.24 +- 2.83 qSH-6*qSH-7 a*a 5 5.80 +- 3.79 qSH-6*qSH-11 a*a 5 8.10 +- 1.24 qSH-7*qSH-11 a*a 6 8.40 +- 0.83 qSH-6*qSH-8 a*a 9 4.88 +- 2.71 qSH-7*qSH-8 a*a 13 4.45 +- 2.71 qSH-11*qSH-8 a*a 4 5.80 +- 2.48 qSH-6*qSH-7*qSH-11 a*a*a 3 3.02 +- 1.54 qSH-6*qSH-7*qSH-8 a*a*a 7 1.55 +- 0.48 qSH-6*qSH-11*qSH-8 a*a*a 6 2.96 +- 2.28 qSH-7*qSH-11*qSH-8 a*a*a 7 1.95 +- 0.67 qSH-6*qSH-7*qSH-11*qSH-8 a*a*a*a 5 1.64 +- 0.44 Notes. Abbreviations RILs recombinant inbred lines RWARA-ZR RILs without any resistant allele in Zhe733/R312 population 1 "a" represents resistant alleles of parent "Zhe733" and "b" represents susceptible alleles of parent "R312". 2 Straighthead rating using a 1-9 scale. Straighthead rating of 4 or below was resistant and 6 or above was susceptible. In the Cocodrie/Jing185 population (Fig. 3B, Table 2), 15 RILs with no resistant allele at both loci (RWARA-CJ) exhibited the highest mean straighthead rating of 8.41. Sixteen RILs with one resistant allele, qSH-3 (RM282), showed a mean straighthead rating of 8.07. Twenty-two RILs with only the resistant allele qSH-8 (AP3858-1) showed a mean straighthead rating of 4.51. Eleven RILs with both qSH-3 and qSH-8 exhibited the lowest mean straighthead rating of 3.62. Significant differences were observed between the RILs with qSH-8 and those with both qSH-3 and qSH-8 and RWARA-CJ, whereas no significant differences were found between RILs with qSH-3 and RWARA-CJ (Fig. 3B). 10.7717/peerj.14866/table-2 Table 2 Genetic analysis of straighthead-associated QTLs in MASA-induced Cocodrie/Jing185 population. QTLs Genotype 1 No. of RILs Straighthead rating 2 RWARA-CJ b*a 15 8.41 +- 0.53 qSH-3 b 16 8.07 +- 0.64 qSH-8 a 22 4.51 +- 1.73 qSH-8 *qSH-3 a*b 11 3.62 +- 1.86 Notes. Abbreviations RILs recombinant inbred lines RWARA-CJ RILs without any resistant allele in Cocodrie/Jing185 population 1 "a" represents susceptible alleles of parent "Jing185" and "b" represents resistant alleles of parent "Cocodrie" at qSH-3 locus, meanwhile, "a" represents resistant alleles of parent "Jing185" and "b" represents susceptible alleles of parent "Cocodrie" at qSH-8 locus. 2 Straighthead rating using a 1-9 scale. Straighthead rating of 4 or below was resistant and 6 or above was susceptible. Agronomic analysis of both RIL populations and straighthead-resistant RILs When we performed water management, we did not observe straighthead symptoms in both parents and in the 91 RILs of the Cocodrie/Jing185 population. This result shows that straighthead was successfully prevented by the water management. The frequency distributions of the four traits, namely, heading date, plant height, tillers, and biomass, were then separately investigated (Fig. 4). The ANOVA results of the four traits show that the four traits significantly differed among the RILs from the Cocodrie/Jing185 population (p < 0.01) (Table 3). 10.7717/peerj.14866/fig-4 Figure 4 Distribution of RILs of Cocodrie/Jing185 population under water-management. 10.7717/peerj.14866/table-3 Table 3 One-way ANOVA of four agronomic traits under water-management. Source Sum of squares Degrees of freedom Mean square F -value P-value Heading days Mean squared between 27,210.667 92 295.768 49.148 4.621E-95** Mean squared error 1,119.333 186 6.018 Total 28,330 278 Height Mean squared between 39,906.708 92 433.769 29.036 1.040E-72** Mean squared error 2,659.144 178 14.939 Total 42,565.852 270 Tillers Mean squared between 15,604.872 92 169.618 2.913 6.816E-09** Mean squared error 10,304.925 177 58.22 Total 25,909.797 269 Biomass Mean squared between 3,55,919.904 92 3,868.695 2.743 1.042E-07** Mean squared error 2,31,262.864 164 1,410.139 Total 5,87,182.768 256 Notes. ** Significantly different from zero at the 0.01 probability level. A total of 27 straighthead-resistant RILs with at least one resistant allele at AP3858-1 were selected for analysis. Afterward, 166 polymorphism markers were used to compare the genetic backgrounds of the selected RILs and their susceptible parent Cocodrie. The results show that five RILs, namely, CJ-404, CJ-407, CJ-479, CJ-480, and CJ-506, shared more than 50% genotypic background with Cocodrie (Table 4), with RIL506 showing the highest genetic similarity at 66.0%. These RILs and the two parents were then subjected to phenotypical similarity analyses using Duncan's multiple test (Tables 5 and 6). Significant differences were observed between the heading days of Cocodrie and all RILs (Table 6). CJ-479 had the longest heading day among the RILs, whereas CJ-480 had the shortest one (Table 5). Significant differences in plant height were also observed between all RILs and Cocodrie, except for RIL480 (Table 6). CJ-479 had the highest plant height, whereas CJ-506 had the shortest one (Table 5). However, no significant differences were observed in the tillers and biomass of the RILs with a Cocodrie background (Table 6). In conclusion, all five RILs with greater than 50% genotypic similarity to Cocodrie showed high yields similar to Cocodrie's. These RILs are potential germplasms for straighthead-resistance breeding. 10.7717/peerj.14866/table-4 Table 4 Genotypic similarity analysis of RILs of MASA-induced Cocodrie/Jing185 population. RILs qSH-3 genotype 1 qSH-8 genotype 2 Ancestry of cocodrie Straighthead rating 3 CJ-404 a a 50.64% 3.67 +- 1.63 CJ-407 b a 53.91% 1.83 +- 0.75 CJ-479 b a 52.42% 2.67 +- 1.03 CJ-480 b a 52.40% 3.50 +- 1.83 CJ-506 b a 66.02% 2.33 +- 1.03 CJ-388 a a 49.62% 3.00 +- 1.26 CJ-427 a a 47.73% 2.00 +- 1.26 CJ-478 a a 44.53% 3.83 +- 1.83 Notes. 1 "a" represents susceptible alleles of parent "Jing185" while "b" represents resistant alleles of parent "Cocodrie"at qSH-3 locus. 2 "a" represents resistant alleles of parent "Jing185" and "b" represents susceptible alleles of parent "Cocodrie"at qSH-8 locus. 3 Straighthead rating using a 1-9 scale. was averaged over 3 replications each year and 2 years for which the SD was estimated. Straighthead rating of 4 or below was resistant and 6 or above was susceptible. 10.7717/peerj.14866/table-5 Table 5 Yield-related characteristics in Cocodrie/Jing185 population under water-management. RILs Heading date Plant height (cm) Tillers Biomass (kg) CJ-404 215.33 +- 0.58 91.44 +- 3.37 22.56 +- 1.83 125.79 +- 17.58 CJ-407 216.67 +- 5.51 88.00 +- 0.94 31.00 +- 3.29 114.24 +- 25.14 CJ-479 236.67 +- 2.89 127.89 +- 2.45 23.89 +- 0.96 155.68 +- 33.06 CJ-480 212.33 +- 1.54 95.78 +- 8.06 25.17 +- 2.59 134.38 +- 10.77 CJ-506 215.00 +- 0.00 65.11 +- 3.01 29.39 +- 8.18 102.73 +- 11.03 Cocodire 223.00 +- 1.00 102.67 +- 2.91 19.89 +- 6.62 147.98 +- 41.26 10.7717/peerj.14866/table-6 Table 6 Duncan's multiple tests of yield-related characteristics in Cocodrie/Jing185 population under water-management. RILs N Duncan grouping 1 Heading date Plant height Tillers Biomass CJ-404 3 B B A A B CJ-407 3 A B B A A B CJ-479 3 D E A A B CJ-480 3 A B B C A B A B CJ-506 3 B A A A Cocodrie 3 C C A A B Notes. 1 Means with the same letter are not significantly different. Discussion With the discovery and application of molecular markers in the late 1970s, MAS has provided a time-saving and purpose-directing strategy for plant breeding that is superior to conventional strategy. Previous studies reported MAS application in different species and traits (Chen et al., 2008; Huang et al., 1997; Li et al., 2018; Zhao et al., 2012). According to our previous report (Pan et al., 2012), the straighthead-resistant QTL qSH-8 accounted for approximately 67% of the phenotypic variations in the Cocodrie/Jing185 population, which is much higher than those of any other QTL. In the present study, AP3858-1 tightly linked to the major straighthead-resistant QTL qSH-8 was used to screen 91 RILs from the Cocodrie/Jing185 population. The results show that 22 RILs with the resistant allele qSH8 (AP3858-1) showed a mean straighthead rating of 4.51 (medium resistant). This result suggests that AP3858-1 is a reliable marker for straighthead-resistance selection. The three other QTLs in the Zhe733/R312 population, namely, qSH-6, qSH-7, and qSH-11, accounted for 13%, 12%, and 8% of the phenotypic variations, respectively. Although the three QTLs accounted for much lower variations than qSH-8, they can still be useful when applied in other genetic backgrounds and can also help us understand the genetic structure of the interest trait. For instance, 49 QTLs for 14 rice traits were reported by Wang et al. (2011), eight of these QTLs were related to spikelet number per panicle and to 1000-grain yield, which account for approximately 8% and 10% of the phenotypic variations, respectively. These QTLs were introduced into chromosome segment substitution lines, which exhibited increased panicle and spikelet sizes compared with their parent 93-11 (Zong et al., 2012). Based on our study, RILs that pyramid all three QTLs showed increased levels of straighthead resistance compared with the susceptible parent R312. This result suggests that the three QTLs can be used in MAS for resistance breeding. In our study, the QTLs were related to MASA-induced straighthead. In previous studies on As-plant interaction, a number of QTLs were identified to correlate with As tolerance (Ehasanullah & Meetu, 2018; Syed et al., 2016; Xu et al., 2017) and accumulation (Song et al., 2014; Wang et al., 2016; Yamaji & Ma, 2011). Interestingly, some of these QTLs shared regions with our straighthead-resistant QTLs in rice. For instance, Syed et al. (2016) reported three QTLs, namely, qAsTSL8, qAsTRL8, and qAsTRSB8, which were associated with shooting length, root length, and root-shooting biomass under As stress, respectively. Wang et al. (2016) reported a gene, OsPT8, that was related to AsV transport in root cells and root-elongation inhibition. Kuramata et al. (2013) reported the qDMAs6.2 gene, which was associated with As accumulation in rice grains. Thus, researchers have already connected straighthead to As accumulation. Yan et al. (2008) reported that the As concentration in the straighthead-resistant cultivar Zhe733 was much lower than in the susceptible cultivar Cocodrie when the two were planted in the same soil condition. Hua et al. (2011) also found that the As concentration in Cocodrie was nearly three times higher than in Zhe733 when the two were grown in MASA soil. Therefore, the straighthead-resistant QTLs may also be tolerant to As stress. These QTLs will help in understanding the mechanism behind As transportation and accumulation in plants. Although breeding for straighthead resistance has been conducted since the 1950s, little progress has been made until 2002 (Yan et al., 2002). One of most important factors was the lack of resistant germplasms in the US. The southern United States produces over 80% of rice, and 90% of the cultivars grown here are tropical japonica (Mackill & Mckenzie, 2002); most of these cultivars are susceptible to straighthead. In previous studies, 42 resistant accessions were identified from a survey of 1,002 germplasms collected worldwide. None of these accessions were japonica (Agrama & Yan, 2010), whereas most of the resistant accessions were classified into the indica subspecies. Possibly, straighthead resistance comes from indica. This resistance would thus be used to improve the susceptible cultivars grown in the southern U.S.. In fact, the two resistant parents in the present study are both from indica accessions. However, incompatibilities between the two subspecies were observed. Straighthead evaluation is based on rice infertility; therefore, the incompatibility made it challenging to obtain well-developed seeds and may have also caused bias when the straighthead resistance of the offspring was evaluated. In our previous research, for instance (Pan et al., 2012), 13 RILs with resistant alleles showed high straighthead ratings in some cases because of the incompatibility between the two subspecies. In the present study, we identified five F9 RILs from the crossing between japonica Cocodrie and indica Jing185. These RILs had the highly straighthead-resistant QTL qSH-8, which is similar to Cocodrie both genotypically and phenotypically. The results suggest that the five F9 RILs, which have both japonica genetic backgrounds and straighthead resistance, are potential lines for developing japonica cultivars for straighthead-resistance breeding. Conclusions This study suggests that qSH-8 is a major QTL for straighthead resistance, and AP3858-1, which is linked to qSH-8, is an ideal tool in marker-assisted breeding for straighthead resistance. Five RILs from the Cocodrie/Jing185 F9 population contained the resistant alleles of qSH-8. In addition, these RILs had more than 50% genotypic background similarities to Cocodrie. Compared with Cocodrie, these lines exhibited significant differences in the heading date and plant height but no significant difference in the tillers and biomass. Most importantly, these RILs exhibited high yields similar to Cocodrie's. The genotypically and phenotypically diverse RILs are potential germplasms that can be used in straighthead-resistance breeding. Supplemental Information 10.7717/peerj.14866/supp-1 Supplemental Information 1 Polymorphic SSR markers linked to the straighthead-resistant QTLs in Zhe733/R312 and Cocodrie/Jing185 populations Click here for additional data file. 10.7717/peerj.14866/supp-2 Supplemental Information 2 Genotype and phenotype in MASA-induced Zhe733/R312 population Click here for additional data file. 10.7717/peerj.14866/supp-3 Supplemental Information 3 Genotype and phenotype of MASA-induced Cocodrie/Jing185 population Click here for additional data file. 10.7717/peerj.14866/supp-4 Supplemental Information 4 Agronomic traits of Cocodrie/Jing185 population Click here for additional data file. The authors thank Hongjun Liu for the critical reviews and Tiffany Sookaserm and Yao Zhou for the technical assistance. Additional Information and Declarations Competing Interests Author Contributions Data Deposition The authors declare that there are no competing interests. 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PMC10000305 | PeerJ PeerJ PeerJ PeerJ 2167-8359 PeerJ Inc. San Diego, USA 14938 10.7717/peerj.14938 Agricultural Science Molecular Biology Plant Science Functional verification of the JmLFY gene associated with the flowering of Juglans mandshurica Maxim. Cai Jiayou 12 Jia Ruoxue 1 Jiang Ying 1 Fu Jingqi 12 Dong Tianyi 12 Deng Jifeng 12 Zhang Lijie [email protected] 1 Shenyang Agricultural University, Shenyang, Liaoning, China 2 Key Laboratory of Forest Tree Genetics, Breeding and Cultivation of Liaoning Province, Shenyang, Liaoning, China Fiaz Sajid 7 3 2023 2023 11 e1493824 10 2022 31 1 2023 (c) 2023 Cai et al. 2023 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. In this study, a pBI121-JmLFY plant expression vector was constructed on the basis of obtaining the full-length sequence of the JmLFY gene from Juglans mandshurica, which was then used for genetic transformation via Agrobacterium inflorescence infection using wild-type Arabidopsis thaliana and lfy mutants as transgenic receptors. Seeds of positive A. thaliana plants with high expression of JmLFY were collected and sowed till the homozygous T3 regeneration plants were obtained. Then the expression of flowering-related genes (AtAP1, AtSOC1, AtFT and AtPI) in T3 generation plants were analyzed and the results showed that JmLFY gene overexpression promoted the expression of flowering-related genes and resulted in earlier flowering in A. thaliana. The A. thaliana plants of JmLFY-transformed and JmLFY-transformed lfy mutants appeared shorter leaves, longer fruit pods, and fewer cauline leaves than those of wild-type and the lfy mutants plants, respectively. In addition, some secondary branches in the transgenic plants converted into inflorescences, which indicated that the overexpression of JmLFY promoted the transition from vegetative growth to reproductive growth, and compensate the phenotypic defects of lfy mutant partially. The results provides a scientific reference for formulating reasonable genetic improvement strategies such as shortening childhood, improving yield and quality, and breeding desirable varieties, which have important guiding significance in production. Juglans mandshurica Maxim. JmLFY gene Functional verification Scientific Research Project of Liaoning Education DepartmentLSNZD201905 Key Project of Liaoning Natural Science Foundation of China20170540801 13th 5-year National Key Research and Development Plan Project2017YFD0600600 Liaoning Province College Students Innovation and Entrepreneurship Training Program2021-114 This work was supported by the Scientific Research Project of Liaoning Education Department (LSNZD201905), the Key Project of Liaoning Natural Science Foundation of China (No. 20170540801), the 13th 5-year National Key Research and Development Plan Project (No. 2017YFD0600600) and the Liaoning Province College Students Innovation and Entrepreneurship Training Program (2021-114). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. pmcIntroduction Flowering is an important process in the life cycle of higher plants. The developmental processes of flowers are divided into flowering decisions, flower initiation, and flower organ development (Zhang & Liu, 2003). During plant flower induction, the external environment and genetic factors together form a complex regulatory network (Zeng et al., 2018; Hassankhah et al., 2018). The model plant Arabidopsis thaliana controls flowering through the interaction of temperature, vernalization, photoperiod, gibberellin, and autonomous pathways (Martina, Nadine & Christian, 2015; Jian et al., 2019; Jin et al., 2019). In the flowering regulatory network of plants, the LEAFY (LFY) gene is a key transcription factor in the flowering signaling pathway, which is expressed in the early stage of flower primordia initiation. The LFY gene determines the floral meristem properties of the flower primordia by activating the expression of floral meristem characteristic genes and floral organ characteristic genes, such as AP1 and CAL. Therefore, the LFY gene is an important floral meristem characteristic gene (Alvarez-Buylla, Garcia-Ponce & Garay-Arroyo, 2006; He et al., 2018). LFY and other genes related to flower formation together form a flower development regulatory network and jointly control plant flower formation. The AtAP1 gene is involved in the formation of flower meristem, which is a characteristic gene of flower organ and plays an important role in the process of flower formation. AP1 and LFY genes are positively regulated by each other. SOC1 gene is the upstream gene of LFY gene, which can integrate multiple flowering pathways; the FT gene is also the upstream gene of LFY gene and the target gene of CO protein; the PI gene is the downstream gene of the LFY gene, and the LFY gene promotes the expression of PI gene (Zhao et al., 2020). The LFY gene plays an important role not only for controlling the transition from inflorescence meristem to floral meristem but also for regulating flowering time in A. thaliana (Weigel et al., 1993; Weigel & Nilsson, 1995; He, Wang & Zhang, 2011; He et al., 2017). When the LFY gene was transferred into wild-type A. thaliana, it was found that all lateral shoots were transformed into flowers (Blazquez et al., 1997). In a functional study of LFY genes in plants such as Populus simonii, Nicotiana tabacum, and Oryza sativa, it was found that transfection and overexpression of LFY gene could lead to earlier flowering (He et al., 2000; Ahearn et al., 2001; Pena et al., 2001). The activity of the LFY gene is conserved even in distantly related species (Shao et al., 1999). Therefore, LFY is not only a key regulatory gene in the plant flowering pathway but also a key regulator of downstream floral meristem and floral organ-determining genes (Feng, Li & Wang, 2016). Although the LFY gene has been isolated and cloned in many plants, functional studies have shown that it plays an important role in the reproductive and growth processes of plants. However, no studies on the LFY homologous gene in J. mandshurica have been conducted. Juglans mandshurica is a dichogamous and monoecious plant with two main mating types, protandrous and protogynous. The asynchronous development and the imbalanced ratios of the female and male flowers affect the efficiency of pollination and fruit setting (Zhang et al., 2019). For the walnut species, the fruit production is also limited by late-spring frost in many countries (Hassankhah et al., 2017), thus the late-leafing and early-harvesting varieties have been studied in Juglans regia by targeted hybridization, and a significant variation between seedlings in terms of leafing date (45 days) were observed, which indicated that it is possible to get late leafing and early-harvesting genotypes with desirable nut traits (Hassankhah et al., 2017; Fallah et al., 2022). Currently, there are few studies focus on the development of male and female flower buds and the asynchrony of flowering period. In J. regia, the flowering pattern was altered by spraying GA3 (the best concentration is 100 mg/L), which increased the total number of flowers, the male flowers, and male: female flower ratio significantly (Hassankhah et al., 2018). However, the molecular mechanism of flower formation in the process of male and female differentiation has not been fully analyzed. Therefore, based on the successful cloning of the JmLFY gene in the early stage of the experiment, a plant expression vector of the JmLFY gene of J. mandshurica was successfully constructed and transformed with Agrobacterium to obtain transgenic A. thaliana plants, and the T0-T3 generations of the transgenic plants were verified and analyzed for the function of the JmLFY gene. This study lays a foundation for the exploration of the molecular mechanism of the flowering of J. mandshurica, and provides a scientific basis for the shortening of the juvenile period, early flowering, yield and quality improvement of J. mandshurica, selection of improved varieties, and rational formulation of genetic improvement strategies. Materials and Methods Plant material The test materials were obtained from the JmLFY gene strain stored in the Forest Genetics and Breeding Laboratory of Shenyang Agricultural University and stored at -80 degC; wild-type A. thaliana seeds (Columbia type) and lfy mutant seeds were purchased from TAIR website ). Experimental reagents BM Seamless Cloning Kit (Biomed, Beijing, China), DH5 a and Agrobacterium GV3101(Biomed, Beijing, China), small plasmid extraction kit (TIANGEN, Sichuan, China), Gel recovery, DL2000 Marker, High fidelity enzyme and LA Taq (TaKaRa, Beijing, China), X-gal and IPTG (Real Times, Shenzhen, China), Bis, Tris Hcl, SDS, TEMED, ammonium persulfate, ammonium persulfate, kana, sucrose, and agar powder (Sinopharm, Beijing, China), and LB medium (ShengGong, Liaoning, China). Acquisition of the JmLFY gene of J. mandshurica The plasmid was extracted from the JmLFY cDNA bacterial solution of J. mandshurica stored at -80 degC, and the full-length PCR gene was amplified using high-fidelity enzymes and specific primers, the primer sequences are shown in Table 1. The PCR products were recovered by cutting the gel using a gel recovery kit and then were sent to Goldwisdom for sequencing. 10.7717/peerj.14938/table-1 Table 1 Primer sequences used in the construction and functional verification of Juglans mandshurica. Primer Sequence (5'-3') Use LFY-F2 CACGGGGGACTCTAGAATGGATCCCGACCCCTTTACTG JmLFY vector construction LFY-R2 AGGGACTGACCACCCGGGTAGAGGGGCATGTGATCACCC JmLFY vector construction LP GAGGAGGAAGTGGTTACTGGG lfy mutant validation RP AAATGCCTACCAAAATTATAACCG' lfy mutant validation LBb1.3 ATTTTGCCGATTTCGGAAC lfy mutant validation JmLFY-F2 AGCACCCTTTCATTGTAACGGA JmLFY expression analysis JmLFY-R2 GTGCTGCTATGGCGACCAAAG JmLFY expression analysis Actin-F ATGCCCAGAAGTCTTGTTCC JmLFY expression analysis Actin-R TGCTCATACGGTCAGCGATA JmLFY expression analysis AtAP1-F GCTCTTAAGGCACATCCGCAC JmLFY functional verification AtAP1-R GCAGAGGGGGAGGCATATTG JmLFY functional verification AtFT-F ATGCCCAGAAGTCTTGTTCC JmLFY functional verification AtFT-R TGCTCATACGGTCAGCGATA JmLFY functional verification AtSOC1-F AGCAGAGTTGTTGGAGACGTT JmLFY functional verification AtSOC1-R AGGTGAGGGTTGCTAGGACT JmLFY functional verification AtPI-F TACAACTGGAGCTCAGGCAT JmLFY functional verification AtPI-R ATTCCTCTTGCGTTGCTTG JmLFY functional verification Construction of JmLFY gene expression vector The plasmid pBI121 was double-digested with XbaI and SmaI, and the gel-recovered product was ligated into the pBI121 vector. The recombinant plasmid pBI121-JmLFY was transformed into DH5a cells and detected by PCR. The positive bacterial liquid that was successfully verified by sequencing was subjected to plasmid extraction, transformed into Agrobacterium GV3101 competent cells, and sent to Goldwisdom for sequencing after PCR. The successfully detected bacterial solution was used to prepare an infection solution. Validation of lfy mutants Resistance validation of lfy mutants of A. thaliana was conducted by kanamycin (KAN) screening, for which seeds of lfy mutants were cultured on 1/2 MS + 15 g/L sucrose + 10 g/L agar + 50 mg/mL KAN. The seeds were cultured at 4 degC for 3 d and then transferred into climatic cabinate, which maintained relative humidity of 60%, temperature of 20-22 degC, light cycle of 24 h and light intensity is 80-200 mmol/m2/s. Homozygosity validation of lfy mutants of A. thaliana was conducted by three-primer method, primers were designed using T-DNA Primer Design ), the sequences of the three primers are listed in Table 1. DNA from leaves of wild type and lfy mutants of A. thaliana were extracted using TIANGEN Plant Genomic DNA Kit, which were then used for PCR. The PCR products were then detected by agarose gel electrophoresis. Agrobacterium-mediated genetic transformation of pBI121-JmLFY to A. thaliana Genetic transformation of pBI121-JmLFY was conducted by inflorescence infection. Seeds of wild-type and lfy mutants of A. thaliana were sterilized and cultured in 1/2 MS medium, and the seedlings were selected and transplanted after 7 to 10 days of germination into the culture soil with robust and consistent growth (Fig. 1A). After bolting and flowering (Fig. 1B), the small pots were inverted, and all the inflorescences were placed upside down in the prepared infection solution, which is described in "Construction of a JmLFY gene expression vector" (Fig. 1C). The transformation was performed every three days and the process was repeated four times, and the mature seeds (Fig. 1D) were collected for obtained regenerated plants. 10.7717/peerj.14938/fig-1 Figure 1 Genetic transformation of Arabidopsis thaliana. (A) Arabidopsis sowing. (B) Arabidopsis flowering. (C) inflorescence infection process. (D) Arabidopsis seed collection. Screening of positive plants The seeds received above were screened on 1/2 MS + KAN plates, and plants with KAN resistance were preliminarily screened. The screened plants were transferred onto the soil, and after 15 days of bolting, the DNA and RNA of the leaves were extracted using DNA and RNA extraction kits (TIANGEN, Sichuan, China), and reverse transcribed into cDNA using a cDNA synthesis kit (ShengGong, Liaoning, China), using cDNA as the template for PCR detection, and successfully detected by qRT-PCR using 2 x SG Fast qPCR master mix (Lablead). Overexpression of JmLFY gene and regulation of other genes related to flowering The plants with high expression of JmLFY were harvested and cultured to the T3 generation using the same method described above. The plants with the highest expression of JmLFY were selected from the T3 generation plants, and the actin gene of A. thaliana was used as the internal reference gene to determine the expression of the flowering-related genes AtAP1, AtFT, AtSOC1, and AtPI. The qRT-PCR primers used are listed in Table 1. Morphological observation and statistical analysis The selected LFY transgenic A. thaliana plants were named L1-L10, and the LFY transgenic lfy mutant plants were named C1-C10. The L-line and C-line plants with high expression of JmLFY were selected and cultured simultaneously with the wild-type and lfy mutants, and the bolting, flowering, and fruit pod formation times of the four lines were observed and recorded. The number of rosette leaves, plant height, and leaf shape and size were recorded and statistical analyses were performed using SPSS and Excel. Results Acquisition of the JmLFY gene related to the flowering of J. mandshurica The plasmid was extracted from the JmLFY cDNA bacterial solution of J. mandshurica stored at -80 degC in our laboratory. Using the JmLFY gene plasmid as the template, the upstream and downstream primers of the JmLFY gene were designed according to the obtained CDS sequence of the JmLFY gene, and the full-length gene was amplified by PCR. The PCR amplification products were sent to Goldwisdom for sequencing, and the sequencing results showed that the JmLFY target gene was successfully obtained from the cDNA-glycerol bacteria. The JmLFY sequence is shown in Fig. 2. 10.7717/peerj.14938/fig-2 Figure 2 Amplification of the JmLFY gene related to flowering in Juglans mandshurica. Construction of the pBI121-JmLFY plant expression vector The PCR-amplified product of the JmLFY gene was cut into a gel and ligated with the pBI121 vector. Sequencing and comparison showed that the homology between the two cDNA sequences reached 99.91%. The resulting plant expression vector was named pBI121-JmLFY and mapped (Fig. 3). 10.7717/peerj.14938/fig-3 Figure 3 Construction of plant expression vector pBI121-JmLFY. lfy mutant validation The three-primer method was used to verify the homozygosity of A. thaliana lfy mutants, and a 1/2 MS KAN plate was used to screen the A. thaliana lfy mutants for resistance. As shown in Fig. 4, the length of the wild-type band was 900 bp and that of the lfy mutant A. thaliana was approximately 800 bp. It can be concluded that the lfy mutant is homozygous for Arabidopsis, which is in line with the expected results (Fig. 5). After screening on a 1/2 MS KAN plate, it was found that the A. thaliana lfy mutant had yellow leaves, could not grow roots and true leaves, and could not survive for a long time (Fig. 6), indicating that it was no KAN resistant and could be used for subsequent transformation validation experiments. 10.7717/peerj.14938/fig-4 Figure 4 Homozygous verification of Arabidopsis. 10.7717/peerj.14938/fig-5 Figure 5 Expected results for Arabidopsis 1-3: PCR products; M: DL5000 marker; WT: wild Arabidosis; HZ: heterozygote; and HM homozygous verification of Arabidopsis. 10.7717/peerj.14938/fig-6 Figure 6 Verification of kana resistance of lfy mutant. Phenotypic observation showed that the inflorescence of the lfy mutant was transformed into secondary branches, with absent petals and incomplete flower development (Fig. 7), while the lfy mutant plants were highly sterile (Zhang et al., 2008). 10.7717/peerj.14938/fig-7 Figure 7 (A-B) lfy mutant phenotype with secondary branch. Screening of positive plants Wild-type and lfy mutant A. thaliana transformed into the pBI121-JmLFY vector were screened for KAN plate resistance. The positive plants grew true leaves and took root on the KAN plate, while false positives did not (Fig. 8). At approximately 20 days, they were transferred to the prepared matrix soil. Five seedlings with the best growth were selected, and the selected JmLFY transgenic wild-type A. thaliana were named L-line plants while the selected lfy mutants A. thaliana were named C-line plants. 10.7717/peerj.14938/fig-8 Figure 8 Positive and false positive plants screened from the T0 generation. After flowering, the leaves were collected from the preliminarily screened lines, and the extracted RNA was reverse-transcribed into cDNA for positive PCR detection. The test results are shown in Fig. 9. L1, L2, L4, L5 and C1, C3, and C4 were found to be positive. The transformation rates of these two strains were not the same, which may be related to the quality of the recombinant plant expression vector and the operation method. 10.7717/peerj.14938/fig-9 Figure 9 Expression of JmLFY transgenic plants. The positive seedlings screened above were subjected to qRT-PCR analysis, and A. thaliana Actin was used as the internal reference gene to analyze the expression of the JmLFY gene in different lines (Fig. 10 and Supplemental File (raw data)). The C4 expression levels were found to be higher. The four harvested strains were continuously cultivated to the T3 generation, and C23, C28, and C7, which had the highest JmLFY gene expression, were screened for further verification. 10.7717/peerj.14938/fig-10 Figure 10 Expression of JmLFY gene in different parts. (A) JmLFY transgenic plant. (B) JmLFY transgenic plants with lfy mutant. Regulation of JmLFY gene on other flowering-related genes To further explore the regulation of other flowering-related genes in A. thaliana by the JmLFY gene of J. mandshurica, Primer-BLAST was used to design quantitative primers, and fluorescence quantitative analysis was used to analyze the expression of each flower-related gene in the JmLFY transgene, JmLFY-transfected lfy mutant, and wild type. Differences in foreign gene expression were found in different transgenic lines (Fig. 11 and Supplemental File (raw data)). 10.7717/peerj.14938/fig-11 Figure 11 Expression of different flowering genes in JmLFY transgenic plants. (A) AtAP1 gene. (B) AtSOC1 gene. (C) AtPI gene. (D) AtFT gene. Compared to the wild type, the expression levels of all the genes related to flower formation in Arabidopsis plants transformed with the JmLFY gene changed, although the changes were different. The expression level of the AtAP1 gene was significantly increased in L23 and C7 plants, but did not change significantly in the L28 line (Fig. 11A). The expression level of AtSOC1 was significantly increased in L23 and C7 plants. The expression level in the L28 line was also increased, and was much higher than in wild-type A. thaliana (Fig. 11B). The expression of AtFT gene was significantly increased in the L23, L28, and C7 (Fig. 11D); the expression of AtPI gene in L23 and L28 lines did not change significantly, although the expression level was significantly increased in the C7 line (Fig. 11C). The flower bud formation time, flowering time, number of rosette leaves, plant height, and number of secondary branches in the T3 generation lines are shown in Table 2 and uploaded as a Supplemental File (raw data). The phenotypes of the four lines were then compared (Fig. 12). The results showed that the flowering time of the transgenic JmLFY plants was significantly earlier than that of the wild type; approximately eight days earlier, the rosette leaves of the L23 and L28 plants were approximately four times lower than those of the wild type, and the plant height, number of secondary branches, and number of cauline leaves were higher than those of the wild type. Compared to the lfy mutant, there was no obvious change, and the flowering time of the transfected lfy mutant was still later than that of the wild-type A. thaliana; however, it was also significantly earlier than that of the lfy mutant by approximately 7 days. The number of rosette leaves in the C7 plant was higher than that of the lfy mutant. Approximately five fewer leaves, four fewer secondary branches, and five fewer cauline leaves (Table 2); transgenic plants have shorter leaves and longer pods than the wild type (Figs. 12H and 12I), and all shoots were transformed into single flowers several times (Fig. 12F), indicating that JmLFY, as a characteristic gene of floral meristem, can control the transition from vegetative growth to reproductive growth. lfy mutants are sterile plants, and the flowers remained intact after the transfer of the JmLFY gene (Fig. 12G). Most of the flowers regained their normal morphology, produced more seeds than the lfy mutant, and produced fewer rosette leaves, secondary shoots, and cauline leaves than the lfy mutant (Fig. 12J). Some secondary branches were also transformed into single flowers, and JmLFY also transformed secondary branches into inflorescences. In addition, JmLFY regulates the expression of other flowering-related genes in A. thaliana and promotes the expression of these genes, indicating that the function of JmLFY may also be related to the regulation of these genes. These results illustrate the important role of JmLFY in flower formation. 10.7717/peerj.14938/table-2 Table 2 Phenotypic data of different strains. Strain Number of rosette leaves Flower bud formation time Flowering time Plant height Number of secondary branches Number of stem leaves WT 13.8 +- 0.84c 31.4 +- 1.14c 37.4 +- 0.55c 25.92 +- 1.12b 4.2 +- 0.84c 5.4 +- 1.14c lfy 23.4 +- 1.14a 41.6 +- 1.14a 49.8 +- 0.84a 29.5 +- 0.46a 12.4 +- 1.14a 16.8 +- 0.84a L23 10.2 +- 0.44d 22.8 +- 0.84d 28.8 +- 0.84d 25.98 +- 1.33b 4 +- 0.71c 4.4 +- 1.14cd L28 9.6 +- 0.89d 23.2 +- 0.44d 29.2 +- 0.84d 26.46 +- 0.48b 4.42 +- 0.84c 4 +- 0.71d C7 18.8 +- 0.84b 37.4 +- 0.55b 41.2 +- 0.84b 25.7 +- 0.64b 7.6 +- 0.89b 11.4 +- 0.55b Note: The values are the means +- standard errors. Different letters in the same column indicate significant differences at P = 0.05 level. 10.7717/peerj.14938/fig-12 Figure 12 Phenotypic study of overexpression of JmLFY gene in Arabidopsis. (A) lfy mutant; (B) WT; (C) L23; (D) left: WT, right: L23; (E) transgenic lines flowering ahead of time; (F) transformation from secondary branch to single flower L28 (G) C7 flower; (H) up: WT down: L28; (I) WT (left) L28 (right); (J) C7 stem leaf. Discussion The transition from vegetative to reproductive growth is an important process in the plant life cycle, and many physiological and metabolic changes and gene regulation mechanisms are involved in this process (Saquib & Li, 2020; Dong et al., 2021). These gene regulatory networks do not exist independently but interact and regulate each other to jointly regulate the flowering process of plants (Lu et al., 2020; Kalve et al., 2020). The LFY homologous gene regulates the formation of floral meristems and organs and is critical for flowering (Bosl et al., 2004). As a transcription factor, LFY regulates the transition of plants from vegetative growth to reproductive growth and is mainly expressed in the apical meristem. Under the control of the 35S promoter, LFY overexpression promotes early flowering and transforms secondary shoots into single flowers (Zhang et al., 2008). Lfy mutants are defective in flowering and inflorescence formation (Mori et al., 2017; Ma et al., 2020). When GhLFY is overexpressed in A. thaliana lfy-5 mutants, lateral shoot secondary buds are transformed into individual flowers and the wild-type flower phenotype is restored (Tang et al., 2016). In this study, the secondary shoots of the transgenic A. thaliana were transformed into single flowers, the mutant plants of the transgenic JmLFY gene exhibited normal petals, the phenotype of the mutant plants was restored to normal, and the seeds produced are more and better quality than the lfy mutant. These results are similar to those of mutant lfy overexpressing the JcLFY gene of Jatropha curcas (Tang et al., 2016) and the EgLFY gene of Eucalyptus grandis (Dornelas & Rodriguez, 2006), indicating that the JmLFY gene can complement the late-flowering phenotype of lfy mutants and promote the transition from vegetative growth to reproductive growth. Plant flower bud differentiation is a complex physiological process regulated by multiple genes (Zhang et al., 2019). In J. regia, expression of FT gene activated downstream floral meristem identity genes including SOC1, and LFY which consequently led to release bud dormancy as well as flower anthesis and induction (Hassankhah et al., 2020). As a master regulator of flowering and floral gene networks, LFY activates downstream floral meristem recognition genes (AP1 and CAL) (Zou et al., 2014). AP1 is a floral meristem signature gene and a direct target of LFY (Ma et al., 2020). AP1 mRNA gradually accumulates after LFY expression (Haughn, 1991). In addition, LFY also promotes the expression of floral organ-specific recognition genes, such as PI, AG, and AP3, as well as the E functional genes SEP1, SEP2, and SEP3. In this study, compared with the wild type, the expression of AtAP1 gene was significantly increased in L23 and C7 plants, but did not significantly change in the L28 line; the expression of AtSOC1 gene was significantly increased in L23 and C7 plants, and the expression level of the L28 line was also higher than that of wild-type A. thaliana. The expression level of the AtFT gene in L23 and L28 was significantly increased; and the expression level of AtPI gene in L23 and L28 lines showed no significant change; however, the expression level was significantly increased in the C7 line. This indicated that the three genes AtAP1, AtSOC1, and AtPI may contribute to the normal flower morphology of C7. Transferring JcLFY into Jatropha curcas caused transgenic plants to bloom seven months earlier (Tang et al., 2016). Pena et al. (2001) transformed the AtLFY and AtAP1 genes into Citrus sinense and Poncirus trifoliata, and found that transformed plants flowered 3-5 years earlier than untransformed plants (Pineiro, 1998; He, Wang & Zhang, 2011; Ma et al., 2019). In the present study, the transgenic A. thaliana L23 and L28 lines flowered six days earlier than the wild-type plants, and the C7 line flowered eight days earlier than the corresponding mutant lfy. These results suggest that JmLFY promotes early flowering in A. thaliana, shortens the vegetative phase, and complements the delayed flowering of the mutant lfy. In addition, the L23 and L28 lines had fewer rosette and cauline leaves than the wild type. And also, the number of clump leaves, cauline leaves, and branches of the transgenic line C7 were higher than those of the wild-type plants but lower than those of the lfy mutant. The results obtained in this study are in agreement with those obtained in A. thaliana (Weigel & Nilsson, 1995), New Zealand radiata pine (Vazquez et al., 2007), rapeseed (Roy, Saxena & Bhalla, 2009) and Jatropha curcas. The phenotypes of plants overexpressing the LFY gene in Tang et al. (2016) were similar. These results confirm that JmLFY can inhibit the vegetative growth of plants, partially complement the phenotypic defects of lfy mutants, and promote the earlier flowering of plants. And in the future research, the Southern Blot method should be considered to better confirm the transgenic plants. Conclusions In this study, the plant expression vector pBI121-JmLFY was successfully constructed using JmLFY cDNA bacterial solution. The three-primer method and KAN resistance screening confirmed that the lfy mutant was homozygous and did not exhibit KAN resistance. Phenotypic observations showed that the inflorescence of lfy mutant Arabidopsis was transformed into secondary branches, with absent petals and incomplete flower development. The lfy mutant plants were highly sterile and produced few seeds. pBI121-JmLFY was transformed into wild-type and lfy mutants to obtain regenerated plants, and the JmLFY-transgenic Arabidopsis and JmLFY-transgenic Arabidopsis were screened for positive seedlings using KAN plates. Expression of the JmLFY gene was screened and plants with the highest levels of expression were those from the L23, L28, and C7 lines. Validation of the T3 generation plants showed that JmLFY also regulated the expression of other flowering-related genes in A. thaliana and promoted the expression of these genes. The JmLFY gene can partially compensate for the phenotypic defects of lfy mutants, and promote transition from vegetative to reproductive growth and early flowering. Supplemental Information 10.7717/peerj.14938/supp-1 Supplemental Information 1 Raw data for Table 2, Fig. 10, and Fig. 11. Click here for additional data file. Additional Information and Declarations Competing Interests Author Contributions Data Availability The authors declare that they have no competing interests. Jiayou Cai conceived and designed the experiments, performed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Ruoxue Jia conceived and designed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft. Ying Jiang conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Jingqi Fu conceived and designed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft. Tianyi Dong performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Jifeng Deng conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, and approved the final draft. Lijie Zhang conceived and designed the experiments, performed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft. The following information was supplied regarding data availability: The raw data is available in the Supplemental File. References Ahearn et al. 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PMC10000306 | = ("Apocynum venetum" OR "Luobuma"). The searched time spans 1987-2022, the type of literature was article and review, and the language was English. Our search strategy did not limit the impact factor of journals and the affiliation of authors. A total of 200 publications were obtained, including 190 articles and 10 reviews, and their full record with the cited references was exported in plain text format. CiteSpace 6.1.3 was used to analyze keywords of the literatures, with the time partition set to 1987-2022, the time slice set to 1, the node types set to keyword, G-index set to 25, and the pathfinder, pruning sliced networks and pruning the merged network were used to trim the atlas. Based on the result of keywords analysis of CiteSpace, the chapter topics were divided into the pharmacological effects and related components of A. venetum, A. venetum fiber, other Apocynum species similar to A. venetum: Apocynum pictum Schrenk, and the ecological value of A. venetum and A. pictum, and the topics were discussed. The discussion on the bioactive components cover the period 2012-2022. Keywords analysis of CiteSpace Keywords represent the core content of an article and provide information on the topic or the important category to which an article belongs. The keywords with high frequency and highly mediated centrality were analyzed and presented in the form of a visual mapping through the Citespace software (Fig. 2). The most frequent keywords from 1987-2022 were Apocynum venetum L. (111), Apocynum venetum leaves (52), Apocynum venetum leaf extract (31). The keywords with the highest centrality before 2018 include Apocynum venetum L. (0.49), component (0.28), hepatoprotective activity (0.27), identification (0.25) and antioxidant (0.23) (Fig. 2A, Table 1). However, after 2018, among the top ten keywords showing the highest centrality, two words that are poorly correlated with Apocynum venetum leaves appeared: Apocynum venetum fiber (0.28) and Apocynum pictum schrenk (0.27). These results implied that the studies before 2018 mainly focused on the components and the pharmacological effects of Apocynum venetum leaves while Apocynum venetum fiber and Apocynum pictum Schrenk have also attracted the attention of researchers in recent years. 10.7717/peerj.14966/fig-2 Figure 2 Keywords analysis of A. venetum. (A) Nodes in the network represent keywords. Node size represents the number of keyword occurrences. Node color: average time to appear, color from white to red, time from 1987 to 2022. (B) Top 16 keywords with the strongest citation bursts. The grey line represents time interval, the yellow line indicates time period in which a keyword was found to have a burst. 10.7717/peerj.14966/table-1 Table 1 The top ten co-cited keywords with highest centrality. Rank Key words (1987-2018) Counts Centrality Key words (2019-2022) Counts Centrality 1 Apocynum venetum l. 75 0.49 Antioxidant activity 4 0.77 2 Component 10 0.28 Acid 5 0.58 3 Hepatoprotective activity 3 0.27 Constituent 7 0.56 4 Identification 9 0.25 Apocynum venetum leaves 20 0.50 5 Antioxidant 6 0.23 Structural characterization 2 0.46 6 Apocynum venetum leaf extract 22 0.20 Oxidative stress 6 0.45 7 Mass spectrometry 2 0.20 Identification 9 0.30 8 Apocynum venetum leaves 37 0.18 Apocynum venetum l. 43 0.29 9 Apoptosis 3 0.18 Apocynum venetum fiber 10 0.28 10 Antioxidant activity 4 0.17 Apocynum pictum schrenk 3 0.27 Based on the keyword co-linear graph (Fig. 2A), the parameter of "burstiness" was set to g = 0.5, minimum duration = 1. Sixteen burst entries were generated. Among them, the words that have kept the outbreak status were oxidative stress (3.93), Apocynum venetum fiber (3.26), identification (2.68) and tolerance (2.0) (Fig. 2B). These data confirmed that apart from the further in-depth pharmacological investigations, the fiber of this plant has recieved attention in recent years. In addition, the ecological value of Apocynum venetum L and Apocynum pictum Schrenk L has attracted increasing attentions. The bioactive components of A.venetum Flavonoids With the deepening of research and the technological improvement in high performance liquid chromatography, mass spectrometry etc., many phytochemicals of A.venetum have been identified and isolated. Some of these phytochemicals were flavonoids such as hyperoside and isoquercetin, which bioactivities have been comprehensively reviewed previously (Xie et al., 2016a; Xie et al., 2016b; Xie et al., 2012). Since then, more studies have reported on the isolation and bioactivities of known and novel flavonoids from A.venetum. The flavonoids isolated from A. venetum since 2012 are listed in Table 2 and their structures shown in Fig. 3. Kaempferol, quercetin, isoquercitrin (quercetin-3-O-b-D-glucose) and astragalin (kaempferol-3-O-b-D-glucose) isolated from A. venetum leaves have significant anti-depressant activities in mice (Yan et al., 2016). Hyperoside isolated from the leaves of A. venetum showed antidepressant-like effect in P12 cell lines which could improve neuronal viability by protecting neurons from corticosterone damage (Zheng et al., 2012). Hyperoside had protective effect on H2O2-induced apoptosis of human umbilical vein endothelial cells (Hao et al., 2016). For acetaminophen-induced liver injury, both hyperoside and isoquercetin exerted hepatoprotective effect by upregulating the expression and activity of detoxifying enzymes such as sulfotransferases (hyperoside could also increase activities of UDP-glucuronosyltransferase) in liver microsomes and inhibited the activity of cytochrome P450 2E1, accelerating the harmless metabolism of acetaminophen. Additionally, isoquercetin could significantly inhibit acetaminophen induced oxidative stress and nitrosative stress (Xie et al., 2016a; Xie et al., 2016b). Isoquercitrin, isolated from the A. venetum leaf aqueous extract exerted anti-obesity effect in high fat diet induced obese mice by inhibiting adenosine 5'-monophosphate-activated protein kinase (AMPK)/sterol regulatory-element binding protein (SREBP-1c) signaling pathway, glucose uptake, and glycolysis flux. C-1-tetrahydrofolate synthase, carbonyl reductase, and glutathione S-transferase P are potential target proteins of isoquercitrin (Manzoor et al., 2022). 8-O-methylretusin (Fig. 3) isolated from A venetum leaves showed antifouling activity (Kong et al., 2014). On the other hand, 4',7-dihydroxy-8-formyl-6-methoxyflavone isolated from A venetum leaves showed high anti-inflammatory activity via significant inhibitory effect on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a) (IC50 values were 9.0 +- 0.7 and 42.1 +- 0.8 mM, respectively) in lipopolysaccharide-induced mouse peritoneal macrophages (RAW 264.7) (Fu et al., 2022). 10.7717/peerj.14966/table-2 Table 2 Flavonoids isolated from A. venetum between 2012 to 2022. Class Compound identified Bioactivity Plant part isolated from Reference Flavonols Tamarixetin 70% methanol extract in A. venetum leaves Gao et al. (2019), Yan et al. (2016) Isorhamnetin 95% ethanol extract in A. venetum leaves Huang et al. (2017) 4'-hydroxy-7-O-(4-hydroxybenzyl)-3-methoxy-6-prenylflavone anti-inflammatory The ethyl acetate -soluble extract of the leaves of A. venetum Fu et al. (2022) Myricetin 75% ethanol extract in A. venetum leaves Zhang et al. (2022) Flavones Luteolin antidepressant 70% methanol extract in A. venetum leaves Gao et al. (2019) Isoorientin Gao et al. (2019) Apigenin Gao et al. (2019) Acacetin Gao et al. (2019) Acacetin-7-O-rutinoside Gao et al. (2019) Chrysoeriol-7-O-glucoside Gao et al. (2019) Chrysoeriol anti-inflammatory The ethyl acetate -soluble extract of the leaves of A. venetum. Fu et al. (2022) 6,7-dimethoxy-4'-hydroxy-8-formylflavone anti-inflammatory Fu et al. (2022) 4',7-dihydroxy-8-formyl-6-methoxyflavone anti-inflammatory Fu et al. (2022) Flavonones Hesperidin 70% methanol extract in A. venetum leaves Gao et al. (2019) Neocarthamin Gao et al. (2019) Bavachin anti-inflammatory The ethyl acetate -soluble extract of the leaves of A. venetum. Fu et al. (2022) Flavonol glycosides Kaempferol-3-O-(6''-O-malonyl)- galactoside 70% ethanol extract in A. venetum leaves An et al. (2013) Kaempferol-3-O-(6''-O-malonyl)- glucoside An et al. (2013) Eriodictyol-7-O-glucoside 70% ethanol extract in A. venetum leaves Zhao et al. (2014) Quercetin-3-O-sophoroside 83% methanol extract in A. venetum leaves Wang et al. (2020) Flavan-3-ols Plumbocatechin A radical-scavenging activity The ethyl acetate fraction of the methanol extract Kong et al. (2014) Isoflavones 8-O-methylretusin antifouling activities Kong et al. (2014) Anthocyanidins Delphinidin 70% methanol extract in A. venetum leaves Gao et al. (2019) Pelargonidin Gao et al. (2019) Malvidin Gao et al. (2019) Peonidin Gao et al. (2019) Cyanidin Gao et al. (2019) Proanthocyanidins Procyanidin c1 Gao et al. (2019) Procyanidin Gao et al. (2019) Chalcones Carthamin Gao et al. (2019) 10.7717/peerj.14966/fig-3 Figure 3 Chemical structures of the flavonoids isolated from A. venetum between 2012 to 2022. Wang et al. (2020) investigated the absorption and metabolism of quercetin-3-O-sophoroside, isolated from the leaves of A. venetum, in rats. The results indicated that quercetin-3-O-sophoroside was completely absorbed in the small intestine and metabolized in the jejunum to sulfated quercetin-3-O-sophoroside, methylated quercetin-3-O-sophoroside, and methylated quercetin-3-O-sophoroside sulfate. Quercetin-3-O-sophoroside was deglycosylated to aglycones by the cecal microbiota to form derivatives of benzoic, phenylacetic and phenylpropionic acids (Wang et al., 2020). To obtain larger amounts of flavonoids, A. venetum hairy roots were induced with Agrobacterium rhizogenes strain Ar.1193, and 117 kinds of flavonoids were detected in the roots. The flavonoid content and antioxidant activity of the roots were significantly increased as compared to field-planted roots, therefore, this technique could be used for large-scale production of flavonoids from A. venetum (Zhang et al., 2021). Polysaccharides Natural polysaccharides have been proved to possess, among other effects, immune regulatory, anti-oxidative and anti-inflammatory activities, as well as having the advantages of being safe and non-cytotoxic (Liu et al., 2022). Zhou et al. (2019) used different concentrations and kinds of solvents (HCl, H2O, NaOH) to extract polysaccharides from A. venetum leaves. The results showed that the polysaccharide yield was the highest with 21.32% (w/w), 0.5 M NaOH at 90 degC, and the bioactivity of the alkaline extracted polysaccharides was the strongest, which was reflected in the antioxidant capacity (DPPH and ABTS radical scavenging activities) and a-glucosidase and lipase inhibitory activities. The 0.5 M NaOH extracted polysaccharides showed a strong inhibitory activity on a-glucosidase (IC50 value of 16.75 mg/mL), which was better than the positive control, acarbose (IC50 value of 1,400 mg/mL). In addition, the alkaline polysaccharide-rich extracts were proved to possess hypoglycemic and hypolipidemic effects on mice with high fat diet induced and streptozotocin-induced type 2 diabetes. Moreover, the extract reversed intestinal dysbiosis by increasing the abundance of Odoribacter, Anaeroplasma, Muribaculum, Parasutterella and decreasing the abundance of Enterococcus, Klebsiella, Aerococcus in diabetic mice (Yuan et al., 2020b). Some polysaccharides were also isolated from various parts of A. venetum and validated for bioactivity. These are summarized in Table 3. ALRPN-1 and ALRPN-2 exerted a significant anti-inflammatory activity in lipopolysaccharide-induced macrophages by regulating the levels of pro-inflammatory mediators (NO) and cytokines (TNF-a, interleukin-6, interleukin-1 b) and the mechanism may involve, in part, extracellular signal-related kinase (ERK)/mitogen-activated protein kinases (MAPKs) signaling pathway (Liu et al., 2022). Vp2a-II and Vp3 obtained from the flowers of A. venetum showed anticoagulant activity and immunoregulation. The anticoagulant activities of Vp2a-II and Vp3 were assayed in vitro by plasma coagulation parameters (activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), fibrinogen). The results showed that Vp3 significantly prolonged TT and PT, while Vp2a-II significantly prolonged APTT and TT, indicating that the two polysaccharides could inhibit blood coagulation (Wang et al., 2019b). In addition, the polysaccharides could exert immunomodulatory effects by promoting phagocytic activity, enhancing NO secretion and mRNA expression of inducible nitric oxide (iNO) synthase, interleukin-6 and TNF-a which activate RAW264.7 cells. Vp2a-II might activate the MAPK signaling pathway, which then induce the nuclear translocation of NF-kB p65 (Wang et al., 2022). 10.7717/peerj.14966/table-3 Table 3 Polysaccharides from different parts of A. venetum. Name Average molecular weight Monosaccharide Bioactivity Mechanism Plant part Reference ALRPN-1 1. 542 x104 Da Glucose Anti-inflammatory ALRPN-1 and ALRPN-2 exert significant anti-inflammatory activity in LPS-induced macrophages by regulating the levels of pro-inflammatory mediators (NO) and cytokines (, IL-6, IL-1 b) and activating the ERK/MAPKs signaling pathway. A. venetum root Liu et al. (2022) Galactose Arabinose ALRPN-2 5.105 x 103 Da Glucose Galactose Mannose Vp2a-II 7 x103 Da - Anticoagulant activity Vp2a-II could inhibit blood coagulation through exogenous pathways and endogenous coagulation pathways. A. venetum flower Wang et al. (2022); Wang et al. (2019a); Wang et al. (2019b) Immunoregulatiory Vp2a-II and Vp3 could activate RAW264.7 cells by promoting cell viability phagocytosis, and enhancing the NO secretion and mRNA expression of iNOS, IL-6 and . Moreover, Vp2a-II and Vp3 could trigger the MAPK signaling pathway and then induce the nuclear translocation of p65. Vp3 9 x 103 Da - Anticoagulant activity Vp3 could inhibit blood coagulation mainly through exogenous pathways and coagulation pathways. ATPC-A mixture (the polysaccharide conjugates contained three components) 5.50 x 104 Da 5.38 x 104 Da 5.67 x 103 Da Mannose Emulsifying properties - A. venetum tea (made of A.venetum leaves) residues Chen et al. (2022a), Chen et al. (2022b) In addition to the pharmacological effects of A. venetum polysaccharides, researchers have also began exploring their other properties. The polysaccharide conjugates (ATPC-A) extracted from A. venetum tea residues with an alkaline solution (0.10 M NaOH) had emulsifying properties and stabilized the emulsion which comprised of amphipathic polysaccharides covalently bound to proteins. The stability of the neat ATPC-A emulsions with a concentration equal to or greater than 1.00 weight % was higher than 5.00 weight % gum arabic during storage at different temperatures and pH values (Chen et al., 2022b). Other phytochemical components of A. venetum Many studies have reported other phytochemicals from A. venetum leaf extracts and their pharmacological effects. The ethanol extract of A. venetum leaf possesses anti-cancer activity. A fraction separated from the extract could inhibit the proliferation of Human PCa cells tumor cells. Lupeol accounted for approximately one-fifth (19.3% w/w) of the components of the fraction and was implicated for the induced cytotoxicity against PCa cells. The fraction and lupeol elicited similar anti-proliferative mechanisms, involving: regulating apoptosis signal molecules (P53, cytochrome c, Bcl-2, and caspase 3 and 8), promoting G2/M arrest through impairing the DNA repair system via downregulating the expression of uracil-DNA glycosylase, as well as downregulating the expression of b-catenin (Huang et al., 2017). In preventing D-galactose-induced oxidative damage in mice, the polyphenol extract of A. venetum was superior to the antioxidant vitamin C (Guo et al., 2020). Within its safe concentration range (0-100 mg/ml), the polyphenol extract of A. venetum inhibited U87 glioma cell proliferation and caused cell apoptosis by affecting and genes of other relevant pathways (Zeng et al., 2019). Additionally, A. venetum leaf extract inhibited doxorubicin induced cardiotoxicity through (protein kinase B) Akt/(B-cell lymphoma-2) Bcl-2 signaling pathway (Zhang et al., 2022). The efficacy and mechanism of action of individual chemical components, as well as their possible synergistic effects, of A. venetum leaf extract need to be further investigated. In addition to flavonoids, polysaccharides and polyphenols, sterols (b-sitosterol, sitgmasterol), triterpenoids (lupeol, uvaol), glycolipids (apocynoside I), natural lignan glycoside (alloside of benzyl alcohol) and amino acids have been isolated from A. venetum (Huang et al., 2017; Sun et al., 2022). A. venetum flowers are rich in free amino acids, accounting for about 3% of the total dried weight, including leucine (13.71 mg/mg), isoleucine (7.86 mg/mg), lysine (2.22 mg/mg), tryptophan (1.67 mg/mg) and valine (1.20 mg/mg) (Jin et al., 2019). Uvaol from A. venetum leaves had potent anti-inflammatory effects on dextran sulfate sodium-induced experimental colitis and lipopolysaccharide-stimulated RAW264 cells (Du et al., 2020). Validation of the activities of other components in A. venetum should be the focus of future studies. A. venetum fiber The fiber of A. venetum has been used in textile and paper industries with superior properties compared to other commonly used fibers. Fiber from Apocynum species has a higher average length to diameter ratio (up to 1219) compared to kenaf (209), another natural plant fiber (Liu et al., 2020; Wang, Han & Zhang, 2007; Xie et al., 2012). Another reason for the popularity of A. venetum fabric is the antibacterial effect that A. venetum fiber naturally possesses (Li et al., 2012; Song et al., 2019). Such antibacterial activity might be because: (i) A. venetum fiber has small openings between microstructures, which improve the breathability of the A. venetum fabric, which subsequently destroy the environment for bacterial growth (Han et al., 2008); (ii) the A. venetum stem cells contain tanning agents, which is resistant to microbial decomposition (Thevs et al., 2012); (iii) the presence of water-insoluble polyphenol derivatives confers antimicrobial properties to the fabric (Xu et al., 2020a). A. venetum is rich in cellulose, but impurities such as pectin, lignin, and waxes must be removed to produce clean fibers (Lou et al., 2019). In the direction of environmental safety and high efficiency, various degumming methods have been proposed, including chemical degumming, biological degumming and microwave-assisted ultrasonic degumming. A study revealed that microwave-assisted ultrasonic degumming showed the advantages of requiring less chemical reagents during degumming (1 kg raw A. venetum bast needed 0.6 kg of reagents while the chemical degumming treatment required 1.34 kg) and shorter time, as well as higher quality (low residual gum content of 5.15%; lignin content less than 3%; whiteness more than 80% in the refined A. venetum fibers) (Li et al., 2020). Degumming methods and the fiber quality of A. venetum reported from 2012 to 2022 are listed in Table 4. 10.7717/peerj.14966/table-4 Table 4 Degumming methods and the quality of fiber obtained from A. venetum (studies between 2012 to 2022). Degumming type Processing method Fiber quality Impact on the environment Reference Bio-chemical combined degumming process Apocynum fibers > > Boiling (12 g/L pectinase, Material: Liquor (M: L)-1:30, time: 2 h, temperature: 50 degC, PH8-10) > > washing > > boiling (12 g/L NaOH, M: L-1:30, time: 1.5 h) > > washing > > bleaching (20 g/L H2O2, M: L-1:30, time: 1.5 h, temperature: 95 degC) > > washing > > oven-dried (temperature: 80 degC) Fiber breaking strength: 22.84 cN/dtex; Whiteness: 73.9; Fineness:4.97 dtex; Crystallinity: 74.5%; Moisture regain: 7.7380%. This method could reduce the pollution caused by chemicals. Chen et al. (2022a), Chen et al. (2022b) Biodegumming (Bacterial strain Pectobacterium wasabiae) Oscillating fermentation (fermentation time: 12 h, inoculum size: 2%, M: L -1:10, temperature: 33 degC, shaking rate:180 rpm) > > boiling (temperature: 100 degC, time: 20 min) > > washing by machine Residual gum content: 12.57%; Percentage of raw material weight loss: 30.05%; The fiber counts:1,002 m/g Chemical Oxygen Demand: 3,119 mg/L Duan et al. (2021) Microwave-assisted ultrasonic degumming Sample > > Microwave pretreatment (10 g/L NaOH, M: L-1:20, time: 20 min, temperature:120 degC, power: 600W) > > rinsing > > drying > > ultrasonic degumming > > soaking (10 g/L NaOH and 1 g/L H2O2, M: L-1:20, time: 60 min, temperature:50 degC, power: 800W, frequency: 28 Hz Residual gum content: 5.15%; Fiber breaking strength: 7.67 cN/dtex; Fiber length:32.5mm; Whiteness: 83%; Fineness: 4.05 dtex; For degumming 1 kg of raw AV bast needed 0.6 kg of chemical reagents Li et al. (2020) Chemical degumming Stripped bast by machine > > pretreatment (0.2%Al2(SO4)3, room temperature, M: :15, time: 7h) > > fiber washing > > cooking (1%NaOH, 0.25% thiourea, M: :15, temperature:95 degC, time intervals:2, 3, 5 h) > > washing > > acid soaking (2% CH3COOH, room temperature, M: :15, time: 2 min) > > washing > > bleaching (2% H2O2, 0.1% tween-80 surfactant, temperature: 94 degC, M: :15, time: 1 h) > > washing > > drying (oven-dried at 105 degC). Moisture regain: 7.0%; The cooking processes of three different time intervals: Residual gum content: 3.64, 3.03, 2.70%, respectively; Crystallinity: 81.14, 78.80 73.75%, respectively; Tenacity: 8.63, 7.00, 6.93 cN/dtex, respectively; Fiber diameter: 2.52, 2.37, 2.14 dtex, respectively. The method uses metal salts of aluminum for pretreatment, which is more sustainable. Halim et al. (2020) Deep eutectic solvents (DES) with the assistance of microwave DES Configuring (choline chloride and car bamide-1:2 molar ratio (w/w) > > oil bathing (temperature: 80 degC, M: :20, time: 1 h) > > immersing with microwave oven (temperature:110 degC, M: :20, time: 1 h ) > > washing > > cooking (1%NaOH, time: 1 h) > > washing > > oven-dried Residual gum content: 6.54%; Fiber breaking strength:14.14 cN/dtex; Crystallinity: 77.92%. Average fiber fineness: 4.05 dtex. DES reagent selected for this method is biodegradable Song et al. (2019) Degumming with Ionic Liquid (IL:1-butyl-3-methylimidazolium acetate-water mixtures.) Pretreatment A.venetum fibers > > pretreatment > > water boiling (temperature: 70 degC, M: :20, time: 3 h) > > rinsing with hot water (60 degC) > > rinsing with tap water > > degumming with IL-water mixtures (80% IL-water mixtures, temperature: 90 degC M: :20, time: 4 h) > >chemical degumming (10 g/L NaOH and 2% Na3P3O10, M: :20 temperature: 95 degC, time: 2 h) > > acid rinsing (1.5 g/LH2SO4, room temperature, M: :20, time: 5 min) > > washing with tap water > > drying Residual gum content: 3.90%; Fiber breaking strength: 452.7 cN/dtex; Fineness: 0.7 um Crystallinity:76.62% Mild conditions and low toxicity. Yang et al. (2019) Chemical degumming Pre-acid treatment (2% H2SO4, temperature: 60 degC, M: :15, time: 1 h) > > washing > > first-cooking (5% NaOH, 3% Na2SiO3, 2.5% Na2SO3, temperature: 100 degC, M: :10, time: 2.5 h) > > washing > > second-cooking (15% NaOH, 3% Na2SiO3, 2% sodium tripolyphosphate, temperature: 100 degC, M: :10, time: 2.5 h) > > washing > > acid rinsing (1 g/L H2SO4) > > washing > > dewatering > > shaking > > drying Fiber breaking strength:401.56 cN/dtex; The average length:29.68 mm; Fineness:4673.25 nm; Color: reddish yellow; Moisture regain: 8.70%; Crystallinity:70.36%; - Lou et al. (2019) Bio-degumming (Pectobacterium sp. DCE-01) Machine rolling preprocessing > > bacteria culture (Pectobacterium sp. DCE-01, temperature: 34 degC, time: 6 h, speed: 180rpm, culture medium: 1.0% glucose, 0.5% NaCl, 0.5% beef extract, 0.5% peptone, and 100 mL water, pH 6.5-7.0.) > > Bacterial liquid preparation (water containing: 0.05% NH4H2PO4 and 0.05% K2HPO4, pH 6.5-7.0) > > fermentation and degumming (temperature: 33 degC, M: :15, bacterial solution: fermentation water-2:100, time: 16 h, speed: 180 rpm) > > boiling (temperature: 33 degC, time: 20 min) > > washing by a fiber washer > > drying Residual gum content: 12.22%; Fiber breaking strength: 5.47 cN/dtex; Chemical Oxygen Demand: 3,245 mg/L Duan et al. (2017) A novel ionic liquid degumming Boiling (1 g/L H2SO4, temperature: 50 degC, M: :20, time: 2 h ) > > washing (until the washings were neutral) > > degumming (80% 1-butyl-3-methylimidazolium acetate, temperature: 130 degC, M: :20, time: 3 h ) > > washing > > drying Residual gum content: 9.80%; Fiber breaking strength: 4.64 cN/dtex; Length:24.44 mm Fineness: 4.10 dtex; Crystallinity:78.66% The degumming process was mild compared to the traditional chemical process. Yang et al. (2015) In addition to the textile industry, A. venetum fiber also has many potential applications in medicine as well as in the construction industry. Microcrystalline cellulose (MCC-N) from A. venetum fibers was shown to have a rougher structure and less macrostructure than commercially available microcrystalline cellulose (MCC-C). MCC-N had a crystallinity of up to 78.63% and a thermal stability comparable to that of MCC-C, which made it suitable as a load-bearing material for composite structures, and could be used in polymer composites with high temperature resistance (Halim, 2021). Furthermore, cellulose nanofibers (CNFs) from A. venetum straw were added into poly lactic acid (PLA), and the prepared PLA/CNFs film did not only improve the wettability and permeability of PLA, but also had superior antibacterial properties (the antibacterial growth inhibition rate on Escherichia coli and Staphylococcus aureus were 96.31% and 92.83% at PLA/6% (w/w) CNFs film, respectively). Then, polyvinyl pyrrolidone was added to this film to form a sustained-release nanofiber membrane (PLA/drug-loaded PVP nanofiber membranes), and a purified sea buckthorn was embedded in the drug-loaded film to evaluate its performance. The nanofiber membrane extended and sustained the release of purified sea buckthorn, and the cumulative release reached a maximum of 75.41%. It showed the advantage of a profile with a high initial release followed by a slow diffusion phase (Wang et al., 2021b; Wang et al., 2019a). In addition, when the hydrogel was prepared with chitosan as the matrix, the addition of CNFs improved the mechanical properties and swelling rate of the chitosan-based hydrogel. As the CNFs was 1.5%, the compressive strength of the hydrogel increased by nearly 20%, the swelling capacity reached 140%. In this form, the antibacterial efficacy against Escherichia coli and Staphylococcus aureus were 98.54% and 96.15%, respectively (Wang et al., 2021a). See Abubakar, Gao & Zhu (2021) for further details on the composition, properties and degumming methods of A. venetum fiber. Other Apocynum species similar to A. venetum: Apocynum pictum Schrenk Due to excessive exploitation, wild A. venetum has declined in recent years. A similar species, Apocynum pictum Schrenk (Apocynum hendersonii Hook) is often used in the market as a substitute for A. venetum due to their similarity in morphological characteristics and geographical distribution. The incorporation of A. pictum may affect the safety and effectiveness of A. venetum (An et al., 2013; Chan et al., 2015; Zheng et al., 2022). Although A. pictum has not been included in the Chinese Pharmacopoeia (Chinese Pharmacopoeia, 2020), some studies have reported that it is an important medicinal plant (Gao et al., 2021; Jiang et al., 2021a). For the quality control of A. venetum and to explore the potential application of A. pictum, some studies compared the similarities and differences between the two species in terms of genome size, flavonoid content, chemical composition and biological activity. The whole genomes of the two species were both small and similar, with 232.80 megabase (A. venetum) and 233.74 megabase (A.pictum). The contents of quercetin, hyperoside and total anthocyanin in A. venetum were much higher than those of A. pictum, which was considered to be the reason for the difference in color between the two species (Gao et al., 2019). Hyperoside could be a suitable chemical marker to distinguish between the two species (Gao et al., 2019). In addition, A. venetum has a better antioxidant activity than A. pictum (Chan et al., 2015). However, recent studies have shown that the flavonoids from A. pictum (quercetin-3-sophoroside, isoquercetin, quercetin-3-O-(6-O-malonyl)-galactoside) and A. venetum (hyperoside, isoquercetin, quercetin-3-O-(6-O-malonyl)-galactoside, quercetin-3-O-(6-O-malonyl)-glucoside, and quercetin-3-O-(6-O-acetyl)-galactoside) both exhibited significant antimicrobial activity against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and the fungus, Aspergillus flavus, but A. pictum was superior to A. venetum in terms of antimicrobial capacity (Gao et al., 2021). Apart from the pharmacological value, in recent years, A. pictum is often studied together with A. venetum because of its high ecological value. The ecological value of A. venetum and A. pictum Phytoremediation is one of the appropriate ways to deal with land problems such as drought, salinity and metal pollution (Pilon-Smits, 2005). Apocynum spp. were selected to stabilize sands and restore the degraded saline lands due to their advantages of easy propagation, resistance to harsh environment, and high economic value (Jiang et al., 2021a; Jiang et al., 2021b). The matured seeds of A. venetum appeared to possess higher drought tolerance than seeds of A. pictum. The simulation of the critical values of Apocynum spp. seeds under PEG-6000 simulated drought conditions are summarized in Table 5. Different PEG-6000 concentrations (0%-35%) was used to simulate natural drought conditions to study the effect of drought stress on the germination of Apocynum spp. seeds. The results showed that low concentrations PEG (0-20%) had no significant impact on the germination rate of Apocynum spp. seeds. However, when the concentration was more than 20%, the germination rates of the seeds were reduced, and the negative impact on A. pictum seeds was higher than that on A.venetum. In addition, after the drought stress was alleviated, the seeds were able to germinate under appropriate conditions (Han et al., 2021; Jiang et al., 2021a). Moreover, the membership function (A mathematical tool for representing fuzzy sets) was used to comprehensively evaluate the drought resistance of A. venetum and another desert economic plant, Lycium ruthenicum, by analyzing the physiological and biochemical indices (the content of chlorophyll a, chlorophyll b, proline and soluble sugar, antioxidant enzyme activity, etc.). The results showed that when the soil moisture content was 9.70%, 6.89% and 5.54%, the drought resistance of A. venetum was stronger than that of Lycium ruthenicum (Wang, 2017). 10.7717/peerj.14966/table-5 Table 5 Tolerance value of Apocynum spp. under Simulated Drought (PEG) and Salt (NaCl, LiCl) conditions. Tolerance value A. venetum A. pictum Reference Simulated critical value (PEG concentration) 29.56% 26.58% Jiang et al. (2021a); Jiang et al. (2021b) Simulated limit value (PEG concentration) 40.16% 39.81% Simulated critical value (NaCl concentration) 431 mM 456 mM Simulated limit value (NaCl concentration) 653 mM 631 mM Simulated critical value (LiCl concentration) 196 mM 235 mM Jiang, Wang & Tian (2018a); Jiang et al. (2018b) Simulated limit value (LiCl concentration) 428 mM 406 mM Low concentration of salt solution (0-200 mM NaCl) had no significant effect on the germination rate of current season mature seeds the two species (Jiang et al., 2021a; Shi et al., 2014). However, another study showed that under 200 mM NaCl stress, the growth and development of A. venetum seedlings were inhibited, the phenotypic characteristics (plant height, root length, leaf length, leaf width) were damaged, and the total flavonoid content decreased. However, salt stress increased the content of quercetin and kaempferol in seedlings (Xu et al., 2020b). In addition, the seeds of Apocynum spp. both exhibited high tolerance to lithium salts during germination, particularly LiCl (Table 5) (Gao et al., 2020; Jiang, Wang & Tian, 2018a; Jiang et al., 2018b). The simulated critical value of A. venetum was as high as 196 mM (Jiang, Wang & Tian, 2018a). To put the salt tolerance of A. venetum into perspective, Brassica carinata, another heavy metal tolerant plant with phytoremediation potential, has a germination rate of less than 50% at LiCl concentration above 120 mM (Li et al., 2009). Notably, the addition of lithium in soil did not reduce the concentrations and antioxidant capacity of total flavonoids, rutin and hyperoside in A. venetum leaves (Jiang et al., 2019). Therefore, Apocynum spp. are suitable for the restoration of degraded saline soil in arid areas, and are promising species in the remediation of lithium pollution in the environment (Jiang et al., 2021a; Jiang et al., 2021b; Rouzi et al., 2018). Conclusions Looking back on the research history of A. venetum, the research focuses mainly on the components and pharmacological effects of A. venetum leaves. At present, many of the pharmacological effects are attributable to flavonoids, however these active components and their synergistic mechanism need to be further studied. In addition to flavonoids, some polysaccharides (Vp2a-II, Vp3) and triterpenoid (uvaol) from A. venetum have also shown pharmacological effects. However, the current research in this area is still lacking. In recent trends, the fiber of A. venetum have attracted attention. Apart from its textile value, the potential application of the fiber in other industries needs further exploration in future studies. The ecological value of Apocynum spp. is gradually being revealed by multiple research. This study provided rich and rigorous CiteSpace analysis on A. venetum. However, as a limitation, we analyzed only the papers written in English, and within the WoS database, therefore it may not be comprehensive enough to reflect the entire research status. For example, we searched a major Chinese scientific literature database, the China National Knowledge Infrastructure (CNKI), and more than 2,000 Apocynum related publications were retrieved, although these were not within the analysis scope of the current study. This further attests to the interest Apocynum species have received from the scientific community over the past decades. Supplemental Information 10.7717/peerj.14966/supp-1 Supplemental Information 1 Raw data analyzed by CiteSpace Click here for additional data file. 10.7717/peerj.14966/supp-2 Supplemental Information 2 Documented subspecies of A. venetum. Source: World Flora Online, Click here for additional data file. We thank Rao Wu for his help during the preparation of this article. Additional Information and Declarations Competing Interests Author Contributions Data Availability The authors declare there are no competing interests. Tian Xiang performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Longjiang Wu performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Murtala Bindawa Isah analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Chen Chen conceived and designed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft. Xiaoying Zhang conceived and designed the experiments, analyzed the data, authored or reviewed drafts of the article, and approved the final draft. The following information was supplied regarding data availability: The datasets analyzed are available in the Supplementary File and at the Web of Science Core Collection: |
PMC10000307 | PeerJ PeerJ PeerJ PeerJ 2167-8359 PeerJ Inc. San Diego, USA 14989 10.7717/peerj.14989 Aquaculture, Fisheries and Fish Science Ecology Mathematical Biology Zoology Climate Change Biology Uncertainties regarding the natural mortality of fish can increase due global climate change Pereira Campos Caroline 1 Bitar Sandro Dimy Barbosa 2 Freitas Carlos [email protected] 1 Instituto Federal de Roraima, Caracarai, Roraima, Brazil 2 Departamento de Matematica, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil 3 Departamento de Ciencias Pesqueiras, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil Zucchetta Matteo 7 3 2023 2023 11 e1498924 8 2022 12 2 2023 (c) 2023 Pereira Campos et al. 2023 Pereira Campos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. The increase in temperature resulting from global climate change can directly affect the survival of fish and therefore population parameters such as natural mortality (M). The estimation of this parameter and the understanding of the uncertainties in its estimates are enormous challenges for studies that evaluate fish stocks. In addition, the effects of increases in temperature may be associated with life strategies. Therefore, the fuzzy set theory was used to evaluate the effects of temperature increase on the natural mortality of fish, considering different life strategies. The model showed that the increase in temperature increased the uncertainties in M estimates for all species, regardless of the life strategy. However, opportunistic species present greater uncertainties in estimates of M compared to equilibrium species. The patterns found in uncertainties of M associated with species groupings by life strategies can be used in holistic approaches for the assessment and management of recently exploited fisheries resources or for those with limited biological data. Climate change Natural mortality of fish Fuzzy theory Uncertainty Life strategies of fish Coordenacao de Apoio de Pessoal de Nivel Superior--CAPESThis work was supported by Coordenacao de Apoio de Pessoal de Nivel Superior--CAPES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. pmcIntroduction Climate change is considered as one of the biggest and most complex environmental and socioeconomic problem of the world at the present time (Portner et al., 2022). Global warming is the result of natural alterations in the climate system and human activities, which contribute to rising levels of greenhouse gas (GHG) emissions (Portner et al., 2022). Scientific evidence indicates that anthropogenic emissions of GHGs are the main cause of the increase in temperature and the biggest culprit in relation to the current environmental imbalance, causing more than half of the observed increase in global average surface temperatures of the planet (Cleugh et al., 2011). The temperature increases on the surface of the planet are among the phenomena with greater predictability and with wide-ranging effects (Portner et al., 2022). Temperature is an important environmental variable, and it is directly related to the survival of many ecothermic animals, especially fish (Baudron et al., 2014). The effects on fish populations can be manifested through changes in abundance, migration patterns and geographical distribution (Baudron et al., 2014; Ficke, Myrick & Hansen, 2007). Oremus et al. (2020) made projections using global climate change scenarios in order to verify changes in the migration and distribution of 779 species of fish from each exclusive economic zone (EEZ) and concluded that tropical countries are more vulnerable to a potential loss of stocks of these species, since these migrate to cooler waters to maintain their thermal comfort. There are patterns that correspond to different life strategies of freshwater and marine fish species (Winemiller, 1989; Winemiller & Rose, 1992; Ropke et al., 2017). The plasticity of species with different life strategies that depend on environmental variations has also been widely studied (Winemiller & Rose, 1992). Researchers have been indicating that species with life strategies characterized as having a large size, high longevity, low growth and low mortality rate are at a disadvantage in terms of temperature increase, due to their higher metabolic rate, and will likely face local extinction (Freitas et al., 2013). On the other hand, smaller species in lower trophic levels can benefit from this potential reduction of predators (Woodward et al., 2016). This shows that the effects of climate change on fish can be of a greater or lesser degree and can have distinct signs, depending on the life strategy of each species (Blanck & Lamouroux, 2007; Ropke et al., 2017). The natural mortality M is one of the most important parameters in the assessment of fish stocks and it is essential in order to estimate the productivity of a fish stock, but it is also one of the most difficult to estimate, due to limitations of data (Punt et al., 2021). The magnitude of error, bias and variance in the estimation of this parameter can be substantial and can be affected by temporal and spatial effects (Kenchington, 2014). Incorporating the uncertainties in the calculation of M estimates is essential to make robust assessments of the fish stock (Brodziak et al., 2011). Most estimation methods for M consider only intrinsic factors of the species: length, maturation size, growth rate and age, without considering the influences of extrinsic factors, such as environmental variables (e.g., temperature) (Kenchington, 2014), which can be determinants in population dynamics and are intrinsically variable (Saether & Bakke, 2000). The method proposed by Pauly (1980) to estimate M includes intrinsic and extrinsic factors, since it estimates M as a function of the von Bertalanffy (1938) growth parameters and the average annual water temperature. It has been shown that the higher the temperatures, the higher the natural mortality rates in fish (Sparre & Venema, 2007). However, the effects of temperature increase, due to climate change, incorporate high variability, which is in part due to the uncertainties existing in the climate models and underlying scenarios (Jeppesen et al., 2014). Thus, it is necessary to apply methodological approaches that incorporate variations and uncertainties in the estimation of parameters. In this sense, fuzzy logic and fuzzy set theory are presented as appropriate tools in the modeling of biological phenomena (Barros, Bassanezi & Lodwick, 2017). This theory was introduced by Zadeh (1965), with the idea of contrasting deterministic models to more flexible models, which enable mathematical modeling of uncertainty, besides mathematically formulating the subjectivity inherent to natural phenomena. Fuzzy logic has been used as a tool in several issues related to the fisheries, such as assessing the vulnerability of marine species (Cheung, Pitcher & Pauly, 2005), assessment of pelagic fishery ecosystems (Paterson et al., 2007), classification of fishing areas (Sylaios, Koutroumanidis & Tsikliras, 2010), spatial management of marine fisheries (Teh & Teh, 2011), behavior of fishers in pelagic fisheries (Wise et al., 2012), stock-recruitment relations (Gutierrez-Yurrita, 2014), parameter estimates of the relationship between weight and length (Bitar, Campos & Freitas, 2016), dynamic of competition among species taking into account abiotic factors and fishing effort (Souza & Bassanezi, 2018), and the fuzzy interactivity in the generalized model of von Bertalanffy (Souza & Prata, 2019). In this study, we assumed two points: (i) the estimate of the average annual water temperature, calculated as a fuzzy number, could, therefore, allow an estimate of natural mortality that incorporates uncertainties in the face of global climate changes; and (ii) the amplitude and intensity of the effects of environmental phenomena could be species-specific (Ropke et al., 2017). We then answered three questions: (i) Will the temperature increases, in the scenarios proposed by the IPCC, increase uncertainties regarding the natural mortality in fish? (ii) Are these uncertainties, if noticeable, the same for marine and freshwater fish species? (iii) Are these uncertainties, if noticeable, the same for fish species with different life strategies? Materials and Methods Study area The area covered in this study was the Brazilian tropical region, including continental and maritime areas (Fig. 1). The main feature of the climate of the tropics is the high average monthly temperatures. However, factors such as latitude, altitude, circulation of air masses and global climate change can cause climate differentiation. 10.7717/peerj.14989/fig-1 Figure 1 Map of the Brazilian tropical zone. The zones indicates watersheds and temperature collection points (river monitoring stations). Classification of life strategies of the target species As an alternative to the concepts of r and k strategists (Pianka, 1970) and based on mechanisms of trade-offs between reproduction, growth and survival of freshwater fish, Winemiller (1989) proposed a classification using three categories of life strategies: equilibrium, opportunistic and seasonal. The classification proposed by Winemiller (1989) gave rise to the triangular continuum of strategies model, which resulted from adaptive responses to environmental predictability and variability. Subsequently, Winemiller & Rose (1992), while studying freshwater and marine fish, confirmed this classification. Basically, these patterns of life strategies suggest that: (1) Equilibrium strategists--These are fish with low growth rates and natural mortality, with a large body size, late first maturation, split spawning, large oocytes, low fecundity, broad reproductive period, relatively high longevity, parental care, which produce larger offspring in low quantities. Since they produce relatively few offspring, survival from the early stages must be high for these populations to persist. These are species that live in relatively stable environments. (2) Seasonal strategists--These are fish that exhibit migratory behavior, absence of parental care, growth rates and natural mortality from intermediate to high, with intermediate to large body size, first maturation is intermediate to late, small oocytes, high fecundity and short periods of reproduction. This strategy would be associated with both temporal and seasonal variations and, if these conditions are favorable, a synchronization in reproduction will occur, guaranteeing juvenile individuals greater chances of growth and survival, in addition to providing a rapid population replacement. (3) Opportunistic strategists--These are fish with a small body size, early first maturation, small oocytes, low fecundity, prolonged breeding period, short life span and with little or no parental care. These characteristics are related to the ability of rapid colonization of environments marked by unpredictable temporal variations. Species selected for the study Species representing the different life strategies were selected according to the classification of Winemiller (1989) and Winemiller & Rose (1992). In addition, we sought to select species from freshwater and marine environments that have been fished for commercial purposes. Based on these criteria, three freshwater and three marine species were selected, each representing a particular type of life strategy. The growth parameters (L and k), of these species can be observed in Table 1. 10.7717/peerj.14989/table-1 Table 1 Population parameters of the species selected for the study, where: L = theoretical maximum length; k = individual growth coefficient; L50 = first maturation; Tmax = longevity. Species L (cm) k (year-1) L50 (cm) Tmax (year) Strategy Environment Cichla temensis 68.05 0.20 31.11 14.00 Equilibrum Freshwater Prochilodus nigricans 34.60 0.44 23.08 6.80 Seasonal Triportheus angulatus 26.78 0.77 16.30 3.89 Opportunist Cynoscion acoupa 142.90 0.13 42.07 10.00 Equilibrum Marine Lutjanus synagris 56.00 0.22 23.00 18.00 Seasonal Sardinella brasiliensis 23.68 0.26 15.80 10.73 Opportunist Note: Sources : 1--Campos, Freitas & Amadio (2015), Campos, Catarino & Freitas (2020); 2--Catarino et al. (2014), Camargo & Lima (2008); 3--Prestes et al. (2010); 4--Oliveira et al. (2020); 5--Aschenbrenner et al. (2017); 6--Costa, Tubino & Monteiro-Neto (2018). Species of freshwater environments: Equilibrium Strategist: Cichla temensis (Humboldt, 1821) Order: Perciformes. Family: Cichlidae The peacock bass, Cichla temensis, has its distribution restricted to the blackwater rivers and their tributaries in the basins of the Amazon River and Orinoco River. It has great importance in the diets of the riparian population, as well as in the ornamental fish trade and, especially, in sport fishing (Soares et al., 2007). In 2003, the peacock bass represented 2.58% of the fishing production that was landed in the main ports of the state of Amazonas (Ruffino et al., 2006) and in the middle Negro River region, and it was the third most landed fish in 2013 (Inomata & Freitas, 2015). It is characterized by a preference for lentic environments, edges of lakes and sandbanks in the main channel of rivers (Winemiller, Taphorn & Barbarino-Duque, 1997). Cichla temensis is a predator at the top of the chain, with a piscivorous habit and it differs among the 15 species of the genus Cichla, since it reaches larger sizes, which can be up to 80 cm and more than 11 Kg (Winemiller, Taphorn & Barbarino-Duque, 1997; Kullander & Ferreira, 2006). The couple builds the nest and, one or both, take care of the offspring (Zaret, 1980; Jepsen, Winemiller & Taphorn, 1999). It presents split spawning, with a long reproductive period and low fecundity (Jepsen, Winemiller & Taphorn, 1999). We used these natural history data to approximate model parameters for major life history characteristics for each of the target species. We considered C. temensis to have low growth rates (k) and natural mortality (M), high values of theoretical maximum lengths (L) and first maturation (L50), as well as relatively high longevity (Tmax). Seasonal Strategist: Prochilodus nigricans (Spix & Agassiz, 1829) Order: Characiformes. Family: Prochilodontidae The curimata, Prochilodus nigricans, is found in the Amazon River and Tocantins River basins (Castro & Vari, 2003). It has significant commercial value and is one of the most caught species in Brazilian continental waters. It is predominant in the landings in Amazonian cities (Batista et al., 2012) in addition to its importance in subsistence fishing (Isaac et al., 2015; Zacarkim et al., 2015). This species inhabits large rivers, flooded forests, lakes and streams, and can be found at any time of the year, even if its abundance varies, due to the influence of seasonal fluctuations in the level of the rivers in the Amazon (Silva & Stewart, 2017). It performs trophic, reproductive and dispersal migrations throughout the year and feeds, basically, on organic debris and periphyton (Silva & Stewart, 2017). Like other migratory fish that feed on detritus, it has access to an abundant source of energy, which contributes to the modulation of carbon flow and productivity of ecosystems (Silva & Stewart, 2017). It is a medium-sized species, between 35 and 50 cm long and is around 3 Kg in weight (Santos, Ferreira & Zuanon, 2006). It has high fecundity, small oocytes and short reproductive period (at the beginning of the rising water period) and does not provide parental care (Silva & Stewart, 2017). In addition, it presents high intermediate values of population parameters, such as growth constant (k), theoretical maximum length (l), natural mortality (M) and first maturation length (L50). Ropke et al. (2017) also classified P. nigricans as a seasonal strategist. Opportunistic Strategist: Triportheus angulatus (Spix & Agassiz, 1829) Order: Characiformes. Family: Characidae A total of 16 species have been described for the genus Triportheus, in which three are well known, Triportheus albus (Cope, 1872), T. auritus (Valenciennes, 1850) and T. angulatus (Spix & Agassiz, 1829), and their occurrences are recorded in the basins of the Amazon, Tocantins and Orinoco Rivers (Malabarba, 2004). In recent years, the demand and commercial interest for Amazonian fish species that are numerous, but of smaller size, has increased significantly. For example, in the 1970s, sardines were infrequently commercialized (Petrere Jr., 1978), but in the past decade, there has been an increase in the volume of landings in the ports of Manaus and Manacapuru, Amazonas state, which has risen from 2% to 12% (Goncalves & Batista, 2008). Triportheus angulatus is a pelagic fish that commonly lives near the surface and close to the banks of rivers and lakes. It has an omnivorous diet that includes insects, zooplankton, fruits and seeds, and it has been verified that, even under conditions of low oxygen concentrations, its feeding activity is not influenced as it has the ability to modify its lower lips to absorb surface oxygen from water (Yamamoto, Soares & Freitas, 2004). Although T. angulatus does not meet some characteristics to be assumed as a typical opportunistic species, it is one of the exploited species by fishing fleets in freshwater systems that shows more characteristics of this type of life strategy, such as small body size, ranging between 20 and 24 cm (Malabarba, 2004); low fecundity and a single spawning (Araujo et al., 2012); no parental care and high growth (k) and natural mortality (M) rates, low value of theoretical maximum lengths (L), small first maturation lengths (L50) and low life span (Tmax). Species of marine environments: Equilibrium Strategist: Cynoscion acoupa (Lacepede, 1801) Order: Perciformes. Family: Sciaenidae The red mullet, Cynoscion acoupa, has a wide distribution and occupies coastal waters from Panama, in Central America, to Argentina, in southern Latin America as well as most of the Brazilian coast (except in the extreme south of the country), both in marine and estuarine environments (Cervigon, 1993). Cynoscion acoupa is the third most landed fish species in Brazil and has a high commercial value due to the quality of its meat and for its swim bladder, which is used as a raw material in the production of emulsifiers and clarifiers (Barletta, Barletta-Bergan & Saint-Paul, 1998). Cynoscion acoupa is a species with nectonic, demersal and coastal habits that lives in shallow and brackish waters under the influence of estuaries and mangroves, which, for this species, are places of refuge, feeding and reproduction (Szpilman, 2011). It feeds mainly on fish and crustaceans and is a large species that can reach up to 130 cm in length and 20 Kg in weight (Ferreira et al., 2016). It has batch spawning, a long reproductive period and high fecundity (a common characteristic for marine species in equilibrium) (Almeida et al., 2016). It has low growth rates (k) and high values of theoretical maximum lengths (L) and first maturation lengths (L50). Its longevity is considered as intermediate to high (Tmax). Seasonal Strategist: Lutjanus synagris (Linnaeus, 1758) Order: Perciformes. Family: Lutjanidae The lane snapper, Lutjanus synagris, has an area of occurrence that extends from North Carolina (USA) to southeastern Brazil (Manooch & Mason, 1984). It is an important fishing resource of tropical marine waters, due to its abundance and quality of meat, which gives it high commercial value and, as a result, it is the target of commercial, artisanal and sports fisheries (Rezende, Ferreira & Fredou, 2003). Lutjanus synagris is a species of demersal habits that lives in warm waters, and is often associated with rocky and coral bottoms, between the coastal zone and out to depths of about 400 m (Pimentel & Joyeux, 2010). It feeds mainly on crustaceans and fish. Considered a medium-sized species, it can reach lengths of between 40 and 50 cm (Pimentel & Joyeux, 2010). It has batch spawning and high fecundity (Grimes, 1987; Freitas et al., 2014). It presents intermediate to slow growth (k), as well as intermediate values of theoretical maximum lengths (L) and first maturation (L50), and is relatively long-lived (Tmax). King & McFarlane (2003) concluded that species of the family Lutjanidae are seasonal strategists. Opportunistic Strategist: Sardinella brasiliensis (Steindachner, 1879) Order: Clupeiformes. Family: Clupeidae The Brazilian sardinella, Sardinella brasiliensis, is a species that is endemic to the southeastern coast of Brazil, and is found along the continental shelf, between Cabo de Sao Tome, RJ and Cabo de Santa Marta Grande, SC (Paiva & Motta, 2000). In terms of volume of production, it is the most important marine fishing resource in Brazil since it is the most commercialized and consumed fish in the country (Paiva, 1997). Shoals occur near the surface, in water up to 80 m deep, and reduce their frequency as the depth increases (Paiva & Motta, 2000). In the region where it occurs, specific oceanographic characteristics are observed, due to the periodic entry of infiltrations from the Central South Atlantic water. These waters act as a fertilization mechanism and provide a greater amount of plankton that favors the survival of the larvae of S. brasiliensis (Matsuura, 1998). It is a species of planktophagous feeding habits (Kurtz & Matsuura, 2001), of small size, ranging from 9 to 27 cm, with a high fertility rate, sequenced spawning and without parental care (Costa, Tubino & Monteiro-Neto, 2018). In addition, it also presents a high natural mortality rate (M) and early maturation (L50), with low values for theoretical maximum lengths (L). Costa, Tubino & Monteiro-Neto (2018) also classified S. brasiliensis as an opportunistic strategist. Data collection To estimate the fuzzy set of natural mortality (M) we use: (i) input variables for the natural mortality equation (M) proposed by Pauly (1980): von Bertalanffy growth parameters (Table 1) of species and annual average water surface temperature (National Water Agency of Brazil (ANA), 2020); and (ii) environmental variable in the modeling: temperature estimates proposed by the Intergovernmental Panel on Climate Change (IPCC, 2014). Average annual temperature The National Water Resources Information System (SNIRH), whose organization, implementation and management are the responsibility of the National Water Agency, divides the national territory into eight large basins: 1--Amazon River, 2--Tocantins River, 3--Atlantic (northern/northeastern stretch), 4--Sao Francisco River, 5--Atlantic (eastern stretch), 6--Parana, 7--Uruguay, and 8--Atlantic (southeastern stretch) (National Water Agency of Brazil (ANA), 2020). The temperature data concerning the basins 1, 3 and 5 (Fig. 1), where the studies of estimation of growth parameters of the species were carried out (Table 2), were obtained and used in the modeling. 10.7717/peerj.14989/table-2 Table 2 Area of study of the target species and their respective basins of origin. Study No Study area Basin 1 Negro River 1--Amazon River 2 Solimoes River 1--Amazon River 3 Solimoes River 1--Amazon River 4 Baia de Sao Marcos 3--N/NE Atlantic 5 Banco dos Abrolhos 5--Eastern Atlantic 6 Costa do Itaipu 5--Eastern Atlantic Note: Sources : 1--Campos, Freitas & Amadio (2015), Campos, Catarino & Freitas (2020); 2--Catarino et al. (2014), Camargo & Lima (2008); 3--Prestes et al. (2010); 4--Oliveira et al. (2020); 5--Aschenbrenner et al. (2017); 6--Costa, Tubino & Monteiro-Neto (2018). IPCC scenarios In 2014, the Intergovernmental Panel on Climate Change (IPCC, 2014) proposed four more simplified scenarios, but using a more complete system, known as RCPs (representative concentration pathways), which use the amount of energy absorbed (radiative forcing, in W/m2) by greenhouse gases (GHG), during or near the end of the 21st century. RCP 2.6: mitigation scenario, which leads to a very low level of absorption; RCP 4.5 and RCP 6.0: stabilization scenarios and RCP 8.5: scenario with very high greenhouse gas emissions (Table 3) (IPCC, 2014). 10.7717/peerj.14989/table-3 Table 3 Features of the RCP scenario of the fifth IPCC report (AR5). RCP Radioactive forcing Concentration CO2-equiv. (ppm) Behavior Rise in sea level (cm) Elevation of TdegC on the planet in 2,100 2.6 Peak of <3 W.m-2 in 2,100 490 Rising with a peak in 2,040 and declining 26-55 0.3-1.7 4.5 Additional storage of 4.5 W.m-2 650 Rising until 2,060 and stabilizing 32-63 1.1-2.6 6.0 Additional storage of 6 W.m-2 850 Rising until 2,100 and stabilizing 33-63 1.4-3.1 8.5 Storage of 8.5 W.m-2 >1370 Rising until 2,100 45-82 2.6-4.8 Note: Source: IPCC (2014). Data analysis Foundations of the fuzzy set theory To understand the modeling process presented in this study, it is necessary to define concepts related to the theory of fuzzy sets. All concepts were defined according to Barros, Bassanezi & Lodwick (2017) and are detailed in Appendix S1. Estimation of fuzzy natural mortality The fuzzy set for natural mortality of each species was performed in four stages: (i) Fuzzy set estimate for average annual temperature: For the fuzzification of average annual temperature, the normality of the data distribution was first verified using the Shapiro-Wilk normality test and its variance. Then, the average annual temperature was modeled as a fuzzy number, from a set of confidence intervals, based on the methodology of Buckley (2005). Buckley (2005) suggests finding the confidence interval 100 (1 - b)% for all 0.01 <= b < 1. Each of these intervals can be denoted by: [th1(b), th2(b)]. The range is considered [th*, th*] for b = 1, where th* it is the point estimate for the parameter th, thus, there are intervals for 0.01 <= b <= 1. These ranges define the fuzzy set th^ through its a-levels as follows: [th^]a=[th1(a),th2(a)]. For 0 <= a < 0.01, [th^]a=[th1(0.01),th2(0.01)] was defined. With this, from the confidence intervals for a parameter th, a fuzzy set for the average annual temperature was constructed whose a-cuts are those intervals. The fuzzy average annual temperature was estimated for each set of temperature data, according to the basin of origin in the study area for each species. (ii) Fuzzy modeling for the temperature variations suggested by the IPCC ( D~i) For each IPCC scenario, a fuzzy average annual temperature was projected. The membership functions, used for each IPCC scenario, were assumed to be the characteristic function of the set of each temperature range, since it is believed that all values of this range have the same importance, since there is no evidence of differences. For each interval Di=[Dmi,DMi], with (i=1,2,3,4) and where Dmi is the minimum value and DMi is the maximum value in the IPPC interval, associated with the temperature variation suggested by the IPCC, a fuzzy set D~i is assigned. Therefore, a membership function is defined to characterize this fuzzy set. We will use the characteristic function (or indicator function) of each set Di. With this configuration, the a-levels of such sets are [A]a=Di, 0<=a<=1. Algebraic operations on these fuzzy sets are performed on their a-levels, based on interval arithmetic (Moore, 2009). These fuzzy sets will be used to estimate the average temperature variation under the influence of variations predicted by the IPCC. (iii) Membership function for average annual temperature values under IPCC scenarios ( T~i, i=1,2,3,4) Let D~i the diffuse variation, associated with scenario i, obtained with the methodology presented above. The fuzzy set estimate for average temperature Ti~, relative to scenario i, will be calculated with the sum of two fuzzy numbers, acocording to the following equation: Ti~=T~D~i, where denotes sum of fuzzy numbers (Barros, Bassanezi & Lodwick, 2017). It is noteworthy that, (Theorem 2.4, Barros, Bassanezi & Lodwick, 2017) [Ti]~a=[T~]a+[D~i]a and, by Theorem 1.4 in Barros, Bassanezi & Lodwick (2017), it is possible to characterize T~i through its a-levels. (iv) Fuzzy set for natural mortality In each scenario, the fuzzy natural mortality was estimated by applying the Zadeh's Extensions Principle (Zadeh, 1965) of the classical function proposed by Pauly (1980): (1) ln(M)=-0.0152-0.279ln(L)+0.6543ln(k)+0.463ln(T) where L, k and T denote theoretical maximum length, individual growth coefficient and average annual water surface temperature, respectively. The procedures for calculating the Zadeh extension are presented in the pseudo code, detailed in Appendix S2. We coded our simulations in Python programming language, version 3.10.6, along with matplotlib, scipy, numpy and pandas packages, on a computer equipped with an Intel(R) Core (TM) i5-2450M and 2.50 GHz CPU. The four stages are contained in pseudocode, and documented in Appendix S2. Results The fuzzy sets for the average annual temperature for the Amazon River basin have a temperature range between 24 degC and 32 degC (Fig. 2A), while the northern/northeastern Atlantic basin has a temperature range of between 26 degC and 33 degC (Fig. 2B) and the eastern Atlantic basin ranges between 19 degC and 30 degC (Fig. 2C). Taking into account the highest degree of membership, that is, 1 (one), the average temperature is 27.3 degC, 28.8 degC and 25.3 degC, for the Amazon River, northern/northeastern and eastern basins, respectively. 10.7717/peerj.14989/fig-2 Figure 2 Fuzzy annual average temperature. (A) Amazon River, (B) Northern--Eastern Atlantic and (C) Eastern Atlantic. Each curve was obtained as fuzzy set to represent the interval of values of temperature. For the three freshwater species, a pattern of increased uncertainty of M with increasing temperature was observed. This uncertainty is most evident between scenarios RCP 2.6 and RCP 8.5. Cichla temensis, which presents strategy in equilibrium, presented the lowest degree of uncertainty of M among the freshwater species (Fig. 3A). Among these species, Triportheus angulatus, that presents some characteristics of opportunistic species, presented the highest degree of uncertainty of M for all scenarios (Fig. 3B). Prochilodus nigricans, a seasonal species, presented an intermediate degree of uncertainty when compared to other freshwater species (Fig. 3C). 10.7717/peerj.14989/fig-3 Figure 3 Distribution of possibilities of natural mortality (M) of freshwater species. (A) Cichla temensis, (B) Prochilodus nigricans and (C) Triportheus angulatus. The vertical bar on the right indicates the degree of membership for each IPCC (Intergovernmental Panel on Climate Change) scenario, after the application of the Zadeh extension. The vertical axis on the left presents the possibilities of M. The bar on the right, in grayscale, presents the degree of membership, and the closer to 1 (one), the greater the pertinence of M.C1 = RCP 2.6; C2 = RCP 4.5; C3 = RCP 6.0; C4 = RCP 8.5 (IPCC, 2014). In the same manner as was presented for the freshwater species, the observed pattern is an increase in the uncertainty of M with the increase in temperature for the three saltwater species, and this is more evident between scenarios RCP 2.6 and RCP 8.5. When the life strategies were compared, Cynoscion acoupa, an equilibrium strategist, presented the lowest degree of uncertainty between the species (Fig. 4A). This increased for Lutjanus synagris (Fig. 4B), which is a seasonal strategist, and Sardinella brasiliensis, an opportunist, presented the highest degree of uncertainty of M, among the species (Fig. 4C). Considering a degree of relevance greater than or equal to 0.05, the a-cut associated with the distribution of the possibility of M for each species and for each scenario of the IPCC can be seen in Table 4. 10.7717/peerj.14989/fig-4 Figure 4 Distribution of possibilities of natural mortality (M) of marine species. (A) Cynoscion acoupa, (B) Lutjanus synagris and (C) Sardinella brasiliensis. The vertical bar on the right indicates the degree of membership for each IPCC (Intergovernmental Panel on Climate Change) scenario, after the application of the Zadeh extension. The vertical axis on the left presents the possibilities of M. The bar on the right, in grayscale, presents the degree of membership, and the closer to 1 (one), the greater the pertinence of M.C1 = RCP 2.6; C2 = RCP 4.5; C3 = RCP 6.0; C4 = RCP 8.5 (IPCC, 2014). 10.7717/peerj.14989/table-4 Table 4 Natural mortality possibilities (M) for each target species in the study and IPCC (Intergovernmental Panel on Climate Change) scenarios, considering a degree of relevance greater than or equal to 0.05. Species Current RCP 2.6 RCP 4.5 RCP 6.0 RCP 8.5 Strategy Environment Cichla temensis 0.48 0.49-0.50 0.51 0.49-0.51 0.50-0.53 Equilibrium Freshwater Prochilodus nigricans 0.98-0.99 0.99-1.02 1.00-1.03 1.01-1.04 1.03-1.07 Seasonal Triportheus angulatus 1.52-1.54 1.53-1.58 1.55-1.60 1.56-1.62 1.59-1.66 Opportunist Cynoscion acoupa 0.30 0.31 0.31 0.31 0.33 Equilibrium Marine Lutjanus synagris 0.52-0.53 0.52-0.55 0.53-0.56 0.54-0.56 0.55-0.58 Seasonal Sardinella brasiliensis 0.74-0.76 0.75-0.78 0.76-0.79 0.76-0.80 0.78-0.82 Opportunist It was possible to identify a general pattern associated with estimates of M, which resulted from IPCC scenarios, and two patterns related to the interactions between the life strategy and the type of environment inhabited by the species. The uncertainty of M increases gradually from one scenario to another, and is consistently higher in RCP 8.5 for all species. However, the variation in the uncertainty is not constant between species with different life strategies. Species in equilibrium have lower uncertainty in estimates of M in all scenarios. Seasonal species present estimates of M with intermediate values of uncertainty, while opportunistic species or with characteristics that come close to the opportunistic strategy, such as T. angulatus, exhibit the greatest uncertainties in the estimated M values for all scenarios, and the variation in the increase in natural mortality is slightly greater for these species. Apparently, species that inhabit freshwater systems have a higher degree of uncertainty of M when compared to marine species. Discussion The difficulty in estimating natural mortality is associated with the number of factors that influence it and the complexity of taking into account all or most of these factors in the estimation process. To minimize this problem, Brodziak et al. (2011) suggested considering the relative influence of intrinsic vs. extrinsic factors and using the estimated distribution of M to provide a more accurate approximation of parametric uncertainties. Our model used temperature as a key factor, which can influence the ratio of metabolic rate and body mass as an intrinsic factor, as well as an environmental and extrinsic factor. Therefore, this can be considered a more robust model compared to the models that have already been used in the attempt to incorporate the uncertainties about M, but that do not combine the two groups of factors that affect M or do not use a force variable that can influence the intrinsic and extrinsic factors (MacCall, 2011; Punt et al., 2021). In a recent study, Dahlke et al. (2020) analyzed 694 freshwater and marine fish species from all climate zones and concluded that 60% of fish species may not survive if climate warming reaches the worst-case scenario, i.e., increasing to around 4 degC. However, for a more optimistic scenario, with an increase of up to 1.5 degC, only 10% of the species surveyed would be at risk in the next 80 years. The physiology of fish is directly related to temperature, which has an inverse relationship with the amount of dissolved oxygen in the aquatic environment (Ficke, Myrick & Hansen, 2007). This inverse relationship (increase in temperature and the reduction of oxygen level) led to an increase in metabolic rate, an increase in physiological stress, and an imbalance in biochemical functions, as well as an increase in the mortality rate of eggs, larvae and adult fish, thus changing the structure, composition and population dynamics of the fish species (Freitas et al., 2013; Barros & Albernaz, 2013). Moreover, the natural mortality is related to body length, asymptotic length, and growth rate (Gislason et al., 2010). The changes in fish populations that are induced by climate change seem to be more noticeable in smaller species with a higher growth rate (Levangie, Blanchfield & Hutchings, 2021). These authors investigated the effects on M of a 10% reduction in the asymptotic length of marine fish species of Canada's Scotian shelf, associated with a 1 degC increase in ocean temperature, and found that species with smaller body size suffered greater increases in M when compared to species with a larger body size. Additionally, considering the 1 degC increase in ocean temperature, Wang et al. (2020) showed that small-sized, fast-growing species were more likely to experience declines in population growth than larger, slow-growing species. These studies corroborate our results, which show that opportunistic species presented the highest M values, in addition to the greatest increases in uncertainty of M (Table 4). The effects of climate change due to an increase in temperature may vary by region and cause adverse environmental events, such as hydrological, oceanographic alterations, as well as extreme climatic events (Marengo et al., 2009). One reason that would explain the additional natural mortality of freshwater species, which in this study are Amazonian species (Cichla temensis, Prochilodus nigricans and Triportheus angulatus), would be the environmental changes associated with extreme climatic events in the Amazon region, such as extreme flooding and droughts (Freitas et al., 2013). The marine species (Cynoscion acoupa, Lutjanus synagris and Sardinella brasiliensis) may have been affected by impacts on coastal circulation patterns, such as coastal resurgences and South Atlantic central water infiltrations (Garcia et al., 2004; Diaz & Rosenberg, 2008; Gruber, 2011). Compared to marine species, freshwater species are more vulnerable to habitat loss, which can result from geographical barriers and environmental degradation induced by anthropogenic actions, such as hydroelectric dams and pollution (Comte & Olden, 2017). In addition, the thermal tolerance ranges of freshwater species are on average 1 degC greater than for marine species, which probably reflects the greater temperature variability in lakes and rivers and greater stability of the oceans (Dahlke et al., 2020), and which could explain the lower number of uncertainties about M for marine species. The uncertainties and variability of estimates of M observed in this study are related to the life strategies of each species. Many aspects of the life history of fish are related to climate on an evolutionary scale, which gives them high or low plasticity, i.e., the ability to adapt to natural changes in their habitats (Val & Almeida-Val, 1995). However, the climate changes that are currently underway are occurring at a higher rate than the adaptation rates, and it is necessary to understand, from the aspects of the life history of a species, if the species has the potential to deal with these changes in the environment (Dahlke et al., 2020; Sunday, 2020), since life history traits are the underlying determinants for population responses to environmental forces (King & McFarlane, 2003). Several studies have been carried out that relate the characteristics of the life history of fish species to temperature in the face of climate change. Studies comparing lake fish from temperate and tropical regions along latitudinal gradients have shown that fish species from lower latitudes are often smaller, grow faster, mature earlier, have a shorter life expectancy, and allocate less energy for reproduction than species from higher latitudes (Blanck & Lamouroux, 2007; Jeppesen et al., 2014; Meerhoff et al., 2012). Jeppesen et al. (2014) conducted a literature review and synthesized the expected changes in the main characteristics of fish life history of inland water systems. In a temperature gradient, species with opportunistic life history characteristics showed greater plasticity compared to species in equilibrium. It has also been shown that the influence of temperature is greater and more significant for fish populations with opportunistic characteristics (faster growth, early age of sexual maturity and shorter life expectancy), than fish with slower life histories, such as species in equilibrium (Free et al., 2019), which was corroborated by our results. King & McFarlane (2003) analyzed the life history characteristics of 42 commercially important fish species from the west coast of Canada. The authors grouped the species by life strategies and made inferences in responses to environmental conditions for fisheries management purposes. They concluded that equilibrium strategists can withstand only low or moderate rates of capture, since they have low fecundity and late maturation and, therefore, are not able to recover as quickly as other fish after population reduction by fishing and, because they have low growth rates, their population dynamics have a very low variability. As seasonal strategists are relatively long-lived, they could benefit from this by ensuring a relatively long reproductive cycle, which minimizes the risk that periods of unfavorable environmental conditions might result in the loss of a stock. However, these species exhibit lower variability in abundance and were classified as having a steady-state population pattern. Opportunistic species occupy habitats not only with a high degree of variability, but also with large energy resources, so their high population abundance variability. These studies corroborate our results about increased variability and uncertainty in natural mortality estimates (M) and, consequently, in regard to population dynamics. The increase in temperature has less influence and, therefore, a lower degree of uncertainty of M for strategists in equilibrium (Cichla temensis and Cynoscion acoupa) regarding climate change. The seasonal strategists (Prochilodus nigricans and Lutjanus synagris) presented an intermediate and/or stationary degree of uncertainty of M and the opportunists or with characteristics that come close to the opportunistic strategy (Triportheus angulatus and Sardinella brasiliensis) presented the highest degree of uncertainty of M. This suggests that the adaptation and plasticity of fish species in order to deal with current climate changes, associated with life strategies, follow a gradient of temperature and natural mortality (M), in addition to a general behavior in the variability of the population dynamics (Fig. 5). 10.7717/peerj.14989/fig-5 Figure 5 Expected behavior according to the characteristics of the life history of fish according to a gradient of temperature (degC) and natural mortality (M) (adapted from Jeppesen et al., 2014). Each groups of species are described by key life history traits. The natural mortality (M) is directly related to the productivity of the stock and the yields that can be obtained, in addition to being one of the most sensitive parameters of fish stock assessment models. Therefore, it is essential to use M estimates that incorporate variations and uncertainties in the face of global climate change. In addition, the patterns found in uncertainties about M associated with species groupings by life strategies can be used in more holistic approaches to the assessment and management of recently exploited fishery resources or those with limited biological data. Supplemental Information 10.7717/peerj.14989/supp-1 Supplemental Information 1 Supplemental Material - Appendices 1 and 2. Click here for additional data file. Additional Information and Declarations Competing Interests Author Contributions Data Availability The authors declare that they have no competing interests. Caroline Pereira Campos conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. Sandro Dimy Barbosa Bitar conceived and designed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft. 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PMC10000311 | Front Psychol Front Psychol Front. Psychol. Frontiers in Psychology 1664-1078 Frontiers Media S.A. 10.3389/fpsyg.2023.957160 Psychology Original Research Gauging response time distributions to examine the effect of facial expression inversion Bimler David L. 1 Paramei Galina V. 2 * 1Independent Researcher, Wellington, New Zealand 2Department of Psychology, Liverpool Hope University, Liverpool, United Kingdom Edited by: Alyssa A. Brewer, University of California, Irvine, United States Reviewed by: Silvia Spadacenta, Hertie Institute for Clinical Brain Research, Germany; Suncica Zdravkovic, University of Novi Sad, Serbia *Correspondence: Galina V. Paramei, [email protected] This article was submitted to Perception Science, a section of the journal Frontiers in Psychology 24 2 2023 2023 14 95716030 5 2022 16 1 2023 Copyright (c) 2023 Bimler and Paramei. 2023 Bimler and Paramei This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Introduction We used images of facial expressions (FEs) of emotion in a speeded Same/Different task to examine (i) distributional characteristics of response times (RTs) in relation to inter-stimulus similarity and (ii) the impact of inversion on FE processing. Methods Stimuli were seven emotion prototypes, posed by one male and one female, and eight intermediate morphs. Image pairs (N = 225) were presented for 500 ms, upright or inverted, in a block design, each 100 times. Results For both upright and inverted FEs, RTs were a non-monotonic function: median values were longest for stimulus pairs of intermediate similarity, decreasing for both more-dissimilar and more-similar pairs. RTs of "Same" and "Different" judgments followed ex-Gaussian distributions. The non-monotonicity is interpreted within a dual-process decision model framework as reflecting the infrequency of identical pairs, shifting the balance between the Same and Different processes. The effect of stimulus inversion was gauged by comparing RT-based multidimensional scaling solutions for the two presentation modes. Solutions for upright and inverted FEs showed little difference, with both displaying some evidence of categorical perception. The same features appeared in hierarchical clustering solutions. Discussion This outcome replicates and reinforces the solutions derived from accuracy of "Different" responses reported in our earlier companion paper. We attribute this lack of inversion effect to the brief exposure time, allowing low-level visual processing to dominate Same/Different decisions while elevating early featural analysis, which is insensitive to face orientation but enables initial positive/negative valence categorization of FEs. facial expressions of emotion inversion effect Same/Different task response times dual-process model ex-Gaussian distribution multidimensional scaling cluster analysis pmcIntroduction Using images of facial expressions (FEs) of emotion, we measured response times (RTs) while participants made "Same"-"Different" judgments on inter-pair similarity. FE pairs were presented both upright and inverted, in the hope that the thus-obtained RT measure would be a sensitive probe of the inversion effect. In the present report, submitted for the Research Topic "Methods and Applications in Perception Science," we focus on RT distributions as functions of inter-stimulus similarity and the stimulus presentation condition. The aim is to analyze latency of stimulus discriminability, in its relation to an accuracy measure, to further explore processes of perceptual decisions underlying comparisons of visually complex stimuli. The problem of determining whether two visual stimuli are identical is a natural activity with ecological implications. In experimental psychology, this function is operationalized as the forced-choice Same/Different (S/D) task, which has been widely used as a convenient psychometric technique for measuring (dis)similarities among a number of stimuli (for reviews, see Farell, 1985, 2022). The S/D task has been applied in a range of domains including schematic facial expressions (Takane and Sergent, 1983); line segments (Young, 1970); abstract symbols (Sergent and Takane, 1987); letters (Podgorny and Garner, 1979); irregular polygons (Cooper, 1976; Cooper and Podgorny, 1976; Smith et al., 2008); or single-syllable words (Farell, 2022). In a S/D task, for N stimuli, the (N2 - N) pairs of different stimuli are each presented some number of times in random order, interspersed with repetitions of the N identical stimulus pairs. The latter provide no similarity information, but in their absence the observers could simply respond "Different" at every trial (though see Becker, 2012; Experiment 2). Non-identical pairs are recognized as such in the majority of trials if exposure times are long enough that inter-stimulus dissimilarities are above the threshold of discrimination. Indices of subjective dissimilarity are the average latency or response time (RT) required to decide that two stimuli differ and the proportion of correct "Different" responses to a given pair (i.e., accuracy). Assuming that median RTs are a function of subjective dissimilarity, a preliminary to later analysis is to determine the nature of that function. Precedents for this postulate include several studies where RTs were related to inter-stimulus dissimilarities provided directly by subjects in the form of ratings (e.g., Young, 1970; Podgorny and Garner, 1979; Paramei and Cavonius, 1999). In one widely-accepted form, this postulate states that for trials where different stimuli are correctly recognized as such, the median RT declines steadily as their dissimilarity increases, "an inverse monotonic function between the reaction time data and underlying distances" (Takane and Sergent, 1983, p. 396). This function slopes down steeply when the dissimilarity is subtle, i.e., a small increment in dissimilarity brings a large reduction in the difficulty of decisions, leveling out and approaching a floor value where the difference between the stimuli is immediately apparent (Cohen and Nosofsky, 2000). Following Shepard (1987), an exponential decline to a constant often fits the function well (e.g., Paramei and Cavonius, 1999). Cooper (1976) reported that an exponential function fitted RTs from the majority of observers, although a minority appeared to apply a different decision process, and their RTs followed a flat function, not varying significantly with inter-stimulus dissimilarity (see also Cooper and Podgorny, 1976). Conversely, "just the opposite relation for [incorrect] "same" judgments was experimentally demonstrated [... implying] that for the "same" judgments, reaction time works as a measure of dissimilarity" (Takane and Sergent, 1983, p. 396). A preliminary objective here is to examine the universal truth of the assumption. Another perspective looks at the entire distribution of RTs and responses for a given inter-stimulus dissimilarity, not just the measure of central tendency, and sets out to derive these from first principles (Balota and Yap, 2011). Of note are random-walk models (Laming, 1968), the diffusion model (Ratcliff, 1978, 1985), the race model (e.g., Huber and O'Reilly, 2003), and others, all falling under the rubric of dual-process decision models. These all agree in postulating two competing "evidence accumulators," one receptive to any points of difference between the stimuli, and the other to the points on which they agree. These "accumulators" function in parallel until one or other function reaches a threshold. When the evidence for a "Same" decision outweighs that for a "Different" decision, or vice versa, then, depending on the metaphor of choice, the scales tip or the race is won. We will use "Different" and "Same" to label the decision processes, and "S" and "D" for the ultimate response. Below, we examine the distributions of RTs for compatibility with dual-process decision models. Naturally this requires a large enough number of trials per stimulus pair (T). Larger values of T also make the average RT more robust, reducing noise from the many hard-to-control variables. There is a trade-off with observer motivation, however, not to mention the danger that observers will learn to recognize each pair as a single Gestalt and provide stereotyped, "over-learned" responses. In previous explorations of RTs as a function of similarity, T has ranged from four (e.g., Roberson et al., 1999, section 5.2), through 10 (Paramei and Cavonius, 1999), up to about 40 or 60 (Mollon and Cavonius, 1986). Much larger values are possible in studies attempting to model the underlying decision mechanisms, which typically examine fewer stimulus pairs. The present study used T = 100. Another aspect of a S/D design is the proportion of identical stimulus pairs. The norm for studies in the S/D paradigm is to present equal numbers of different-stimulus trials (e.g., Qiu et al., 2017). Smith et al. (2008) reported that in a situation with about 50% of identical-pair trials, most human subjects followed a "zero-tolerance" decision strategy, responding D to any detectable disparity. In contrast, macaque monkeys appeared to impose a non-zero threshold, responding S or D to disparities below or above this threshold (as if comfortable with a high number of false-"Same" errors). This can be understood as the Different and Same processes of a decision model having separate thresholds to attain. The thresholds can be manipulated by the experimental design: Ratcliff and Hacker (1981) influenced the RTs and relative numbers of D and S decisions by instructing observers to exercise greater caution before one response or the other. Downing (1970) influenced RTs by manipulating the proportion of trials where the stimuli were identical (50% vs. 25%). In Smith et al.'s (2008) experiment with humans, different-stimulus trials slightly predominated (54%) over same-stimulus pairs. As a precedent, in Wise and Cain's (2000) study about 20% of pairs were identical. Following Krueger and Shapiro's (1981, p. 576) reasoning, it is likely that variation in the ratio of different-stimulus pairs ("heterogeneity of difference") would shift the perceptual decision criterion. Specifically, they argued that decreasing the proportion of same-stimulus pairs reduces the amount of sensory evidence required to assign the S response, thus, resulting in greater number of false-"Same" errors. Indeed, when Smith et al. (2008) manipulated the ratio of . different-stimulus pairs (30:35 vs. 40:35) in macaque monkeys, this induced a large shift in tolerance of stimulus disparity in a monkey presented with the 40:35 proportion of identical pairs, i.e., a looser, more inclusive criterion for responding "Same." This finding is relevant to the present study due to the relatively low proportion of stimulus pairs (7%) which were identical. In research on FEs of emotion, S/D accuracy data have been interpreted as dissimilarities and used to locate the category boundary between distinct emotions (Calder et al., 1996; Roberson et al., 1999; Suzuki et al., 2005). Such data are also suitable for multivariate analyses such as multidimensional scaling (MDS) and hierarchical cluster analysis, employed to reconstruct the perceptual framework underlying the stimuli, in order to glean clues as to (dynamics of) their cognitive representation. The present study examined RTs for "Same" and "Different" judgments among images of FEs presented as pairs in upright and in inverted mode. Stimuli contained prototypical posed expressions of emotions and morphed intermediates. We estimated and scrutinized RT functions for individual subjects, while probing the effect of stimulus inversion upon the encoding and processing of FEs in terms of proximities among them in a spatial model. In particular, we asked whether the inversion impacts more upon some emotions than others; and whether, after inversion, emotion categories still modulate the perception of FEs. A previous MDS analysis of response accuracy in the same experiment (Bimler et al., 2013) found unexpectedly little effect from inversion, and one question we examine here is whether the RTs, as a complementary behavioral measure of (dis)similarity, reveal more effect when examined with the present approach. Materials and methods Participants Two male and two female undergraduate Psychology students, aged 21-25 years, were reimbursed for participation. All participants were right-handed and reported normal vision. Participant sex and poser gender were counterbalanced to offset any possible own-gender bias effect in face recognition (cf. Wright and Sladden, 2003). That is, stimuli from the MO series (from a female poser) were presented to one female participant (DK) and one male (HK). Likewise, the WF series (from a male poser) was presented to one female participant (SB) and one male (BF). Each participant completed 30 1-h-long sessions spread over 4 months; for HK and SB these were interrupted by a three-month gap during their summer vacation. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Stimuli Fourteen grayscale photographs of emotional expressions were selected from Pictures of facial affect (Ekman and Friesen, 1976). Those authors deemed these 14 images to be good examples of seven universal emotion categories in unalloyed form [Happiness (H), Surprise (Su), Anger (A), Sadness (Sa), Fear (F), Disgust (D), Neutral (N)], as evinced by high accuracy of labeling. Seven images featured a female poser identified as MO while the other featured a male poser WF. . Figure 1 Median RTs for each of the four participants (A-D) as a function of run, for D responses (blue lines) and S responses (red lines), with Upright and Inverted stimuli (solid and dashed lines respectively). MO series: participants (A) DK, (B) HK; WF series: participants (C) BF, (D) SB. The MO series and WF series were both extended by using image-interpolation software (Design Studio) to create eight ambiguous intermediate stimuli, each lying midway along the continuum defined by two emotion exemplars as end-points. The morphing process involves 'landmarks' located within each prototype, allowing smooth interpolation of intermediate stages along a transformation between them (cf. Calder et al., 1996; Young et al., 1997). Using morphs between all 21 (7 x 6/2) pairs of "parent" exemplars would have made data collection impractical, so eight pairs were chosen, following a distorted circumplex that paired each exemplar with its neighbor (e.g., SaN, DF), except for Anger, which is paired with Happiness (AH) and Surprise (ASu). Each set, MO and WF, included 15 images. These digitalized stimuli were presented on a 19" CRT-Monitor (V7 N110s), where each image occupied 12.8 cm x 8.7 cm (subtending 10deg x 6.7deg at a viewing distance of 74 cm). Measured with a LMT L1009 Luminance Meter, image luminance ranged from 0.23 to 82 cd/m2. Ambient lighting in the test room was in the mesopic range (around 10 cd/m2). Procedure Each trial consisted of the simultaneous parafoveal presentation of two FE stimuli, symmetrically side-by-side on the screen with a 3.8 cm gap between them (subtending 3deg). After 500 ms, the screen went blank until the participant responded "Same" (S) or "Different" (D) via a two-button keyboard. Instructions described the stimuli as "emotional faces," to focus the participants' attention on their emotional content. Participants were instructed to respond as quickly and correctly as possible. RT was measured (to the nearest 20 ms) from the appearance of the FE pair to the response, by a MS-DOS program running on a Windows-98 PC which controlled presentation and recorded each S or D response. Each response was followed by an inter-stimulus interval of 300-400 ms, while a small red fixation cross was displayed on the monitor. In a single run, all possible 15 x 15 = 225 pairings of FEs were presented in randomized order. Blocked presentation was used, alternating between blocks of all Upright (U) or all Inverted (I) pairs. For each participant the experiment began with a practice session of one block in each of the U and I modes. There followed 10 sessions containing six blocks and 20 containing seven blocks, totalling to 100 runs with FE pairs in the U mode and 100 runs in the I mode. Note that 15 of these 225 pairs were indeed identical (7%). The remaining pairs consisted of "left-right" and "right-left" presentations of 105 pairings. These were treated as repetitions in the analysis, ignoring any asymmetry effects. Participants received no indication about how frequently to expect identical pairs, and no feedback about accuracy after trials. Results Learning effect Before further analysis, the data require some rescaling to compensate for any learning effect. Median RTs in each run are plotted for the four participants separately in Figure 1. Clearly these values change across the course of data collection, with some participants showing substantially shorter RTs with accumulated practice (for HK and SB, the abrupt increase in RTs after the 40th trial reflects their summer interruption). A natural concern is the possibility that RTs for a given pair varied systematically in the course of the experiment relative to other pairs, as subjects became familiar with the stimuli. To test this, we plotted cumulative sums of RTij* for representative stimulus pairs, across a range of similarities . RTij* is defined in the next paragraph. The lines are reasonably straight and do not cross, implying that RTs remained quite stable relative to the median at each run. Thus, Figure 2 shows that changes from learning were across-the-board and did not change the relationships among pairs: if a pair evoked a relatively rapid response in the initial runs, it was still relatively rapid at the end of the experiment. However, this progressive change increased the variance of the distribution of RTs for a given pair of FEs. Figure 2 Cumulative sum of RTij*(r) across 100 runs for 11 representative stimulus pairs (exemplified by data for DK, Upright stimuli). RTs as a measure of FE inter-stimulus similarity Following Ratcliff et al. (2010), median RTs for each FE pair were obtained separately for D and S responses, MijD and MijS . U and I mode trials were analyzed separately. The median value is preferable to the mean, being unaffected by the skewed distribution of RTs or the outlying, exceptionally delayed responses that sometimes occur. As noted, participants' response speed varied as the runs progressed, typically improving with practice. To remove this source of variance, before calculating their medians the 225 RTs in each run r (1 <= r <= 100) were rescaled with a factor s(r) to bring their median value into line with the global median over all runs for that participant: RT*ijr=srRTijr where s(r) = global median(RTij)/median(RTij(r)). We also performed the same analyses without this adjustment, but found no impact on the overall tenor of the outcomes. Errors occurred relatively often with observers responding S in about 25% of the trials (cf. 7% of actually identical pairs). The percentage of erroneous D judgments for a given pair served as a proxy for the perceived dissimilarity between those stimuli, and was constant across runs. In a companion paper we processed accuracy rate (percentages) of S judgments as an index of pairwise perceptual similarity with non-metric multidimensional scaling (MDS) for error-smoothing purposes, embedding them within a four-dimensional geometrical space (Bimler et al., 2013). RTs to identical FE pairs First, we explored RTs to identical pairs of FEs, separately for Upright and Inverted conditions. The (objectively) identical pairs of the MO series stimuli most rapidly identified as "Same" were H-H, FSu-FSu, and Su-Su, while the slowest pairs were N-N, SaN-SaN, ASu-ASu and Sa-Sa. For the WF series, the pairs with the shortest "Same" RTs were H-H, F-F, and A-A, while the slowest pairs were N-N and DF-DF. These outcomes concur with Becker's (2012) report that in a S/D task, matched pairs of negative images took longer to recognize as identical than neutral or positive-affect pairs, a finding attributed to greater demands of processing negative expressions. However, that the most rapidly processed stimuli are marked not so much by their positive affect, but rather by the clarity of a single feature (e.g., WF's exaggerated smile for Happiness, or MO's elevated eyebrows and open mouth for Surprise). That is, the results are consistent with the observers noticing that the stimuli of a pair share a specific exaggerated feature, apparently tipping the scales toward a S response and curtailing further thought. This finding is also in accord with Calvo and Nummenmaa's (2011) conclusion that early (and later) expression discrimination decisions are based on visual saliency of distinctive facial features. RTs of "Different" vs. "Same" responses to FE pairs Median RTs for S responses ( MijS ) were slightly longer than for D responses ( MijD ), as is evident in Figure 3 that plots MijD on the horizontal axis against MijS for the same pairs on the vertical axis. The slower S responses indicate a more conservative decision criterion, in accord with previous findings: S responses (conjunctive judgments) imply accumulating more evidence before making the decision whereas for D responses (disjunctive judgments) a decision is made as soon as any difference is detected (see Farell, 1985, for a review). The delay in the S responses--mean( MijS - MijD )--is not constant for all stimulus pairs but varies as a function of pairwise dissimilarity. In addition, mean( MijS - MijD ) varies from subject to subject, with the largest average delay for BF and DK (90 and 95 ms, respectively) and least for SB (27 ms). It is possible that these inter-individual differences in the delay of S responses are spurious, since in RTs of HK and SB there was an abrupt increase after the summer interruption (we are indebted to a reviewer for this caveat). Figure 3 Median RT* MijS for S responses to i-th and j-th FEs, i j (vertical axis), plotted against MijD for D responses (horizontal axis). Superimposed results for four observers and for both Upright and Inverted presentation modes. Pairs omitted if four or fewer responses. RT distributions: Dual-process model Considering RTs from the dual-process perspective, their distributions become relevant to the possible effects of inversion. In the dual-process paradigm, one can imagine the response to a given stimulus pair (i,j) as a Bernoulli model, where the visual system reports to the Same and Different processes at a regular rate (i.e., at regular clock ticks), and each report has a constant chance of being Same and Different, this chance depending on how many features the stimuli share (cf. Ratcliff, 1978). The decision process continues until the Same or Different detector has accumulated enough reports to trigger either a S or D response, respectively. Figure 4, using observer DK as example, shows the combined distribution of RT*(i,i) for FE pairs varying in subjective (dis)similarity, separately for the Upright and Inverted mode. Figure 4A shows the distribution of RT*(i,i) for the 15 identical-stimulus pairs. These pairs (i,i) evoke the Same process without interruption from D responses and the S threshold is almost always reached. Figure 4B shows the combined RT*(i,j) distributions for 10 pairs which were most distant in DK's accuracy-based MDS solution. Conversely, the Different process manifests in isolation in this case of pairs of greatest dissimilarity, where the D threshold is almost always reached (RTs for the 15 identical pairs were pooled here, as were the 10 most-dissimilar pairs, to reduce statistical noise in the histograms.) The Bernoulli model predicts S and D RTs to follow negative binomial distributions, positively skewed, if the accumulation of reports is uninterrupted. As predicted, for DK , both distributions are positively skewed with a long "tail" of delayed RTs. Figure 4 RT*(i,j) distributions for observer DK, for FE pairs presented Upright (positive values on the y-axis) and Inverted (negative values on the y-axis). The four graphs illustrate RT* (i,j) distributions for pairs that vary in the degree of inter-stimulus similarity. (A) S responses for 15 identical pairs; (B) D responses for 10 most-different pairs; (C) S responses for 10 intermediate-similarity pairs; (D) D responses for 10 intermediate-similarity pairs. The situation is more complicated for pairs of intermediate dissimilarity. Figures 4C, D plot the RT*(i,j) distributions for erroneous S and correct D responses, combining 10 pairs (i,j) lying within a band of intermediate distances, chosen so that errors were closest to 50% of responses, i.e., these were pairs for which the dual-process competition was seemingly strongest. When the reports from the visual system have equal probability of being S and D, the Same and Different functions accumulate at only half the rate as in the extreme cases, predicting longer-delayed and therefore less skewed negative binomial distributions. But an additional factor is at play. The probability of a S conclusion after some time t is reduced by the cumulative probability that a D response had already emerged at any time < t (so the theoretical S distribution is modulated by the cumulative distribution for the Different process). Conversely, the distribution of D responses for these pairs is shaped by the cumulative distribution of the Same process. Details of this two-way interaction depend on the relative speed of the two processes, among other factors, which might make these specific distributions most sensitive to any effects of inversion. Past RT data have been successfully modeled by an exponential-Gaussian function with parameters m, s, t (e.g., Heathcote et al., 1991, 2019; Balota and Spieler, 1999). Accordingly, we applied the "timefit" function from the "retimes" (package for R), to S response RT*(i,j) values to identical pairs (exemplified by data for participant DK, U mode), as in Figure 4A. The matches between the resulting ex-Gaussian functions and actual distributions for this participant are gratifyingly close , validating the data transformation and suggesting that median values are valid measures of central tendency. Table 1 shows the function parameters and the corresponding moments (mean, standard deviation, skewness) for all observers. Note that in line with previous findings (e.g., Heathcote et al., 1991; Balota and Spieler, 1999), the ex-Gaussian characteristics of individual participants are relatively stable regardless of the mode of FE presentation. Figure 5 RT*(i,j) distributions for 15 identical pairs (solid lines) with superimposed ex-Gaussian functions (dotted lines) for observer DK, and Upright (left) and Inverted (right) presentation mode. Table 1 Parameters (m, s, t) for fitted ex-Gaussian functions and moments (mean, SD, and skewness) for the distributions of S RTs for identical FE pairs in Upright and Inverted mode of presentation, for each observer (Ob). Mode Upright Inverted Obs m s t Mean SD Skew m s t Mean SD Skew DK 0.528 0.043 0.086 0.614 0.096 1.439 0.529 0.048 0.078 0.607 0.092 1.250 HK 0.519 0.046 0.080 0.598 0.092 1.291 0.522 0.043 0.090 0.611 0.099 1.461 BF 0.560 0.044 0.061 0.621 0.075 1.070 0.565 0.046 0.054 0.619 0.070 0.886 SB 0.736 0.067 0.058 0.794 0.089 0.558 0.735 0.056 0.067 0.802 0.087 0.910 Non-monotonicity of the RT function Figure 6 plots each observer's median RTs MijD and MijS against inter-stimulus dissimilarity (i.e., inter-point distance in that subject's accuracy-based MDS solution; cf. Bimler et al., 2013). To indicate the reliability of data-points, the size of each symbol represents the number of decisions on which that median is based. Figure 6 Median RT* of "Same" responses, MijS (red symbols), and "Different" responses, MijD (blue symbols), as a function of distance in the accuracy-rate based MDS solutions. * = Upright mode; # = Inverted mode. Symbol size represents number of responses to pair (i,j). Data for individual participants: (A) DK, (B) HK, (C) BF, (D) SB (note difference in the y-axis scale). The unexpected feature is that the MijD values follow a peaked function rather than an exponential decline or any other monotonic function (see also Paramei et al., 2009). This is particularly clear in the results for HK, Figure 6B, who took longest to make a D response for an intermediate dissimilarity of about dist = 6 (arbitrary units in the MDS solution). As expected, more-distant pairs were judged in less time, but so were more-similar pairs. The other three observers exhibit comparable non-monotonicity for MijD . The MijS distributions also follow a non-monotonic contour, though with slightly larger values, the relative delay varying from subject to subject. The shape is less clear because there were very few S responses for highly-dissimilar pairs, so that S points at the right of each panel of Figure 6 are based on only a few atypical responses, limiting their reliability. We note that SB consistently took 300 ms longer to respond than the other participants , although the pattern of her RTs is no different. Until further observers are tested, we do not know whether SB is anomalous or at the conservative end of a range of processing-criteria variation, causing a more exhaustive, attention-strengthened comparison strategy with greater cognitive control (cf. Moret-Tatay et al., 2016). Filtering RT data prior to calculate MDS solutions For further analysis we applied MDS to estimates of similarity derived from median RTs. The solution represents stimuli as points in the spatial model, where the proximity of any two points mirrors the corresponding stimulus similarity, and dimensions indicate attributes underlying the perceptual judgments. To compensate for the non-monotonicity of MijD as functions of reconstructed distances, we filtered their values to the range where they were monotonic, by abandoning all entries for stimulus pairs (i,j) that were similar enough for fewer than 33% of trials to return D responses (the exact threshold is not crucial). The result is a similarity matrix SIM_D for each observer and each presentation mode, where the matrix elements are sim_dij: sim_dij=MDijif fraction ofDresponses<33%=missingdataotherwise The effect is to retain only pairs from the right-hand side of each panel of Figure 6, i.e., the ones that contain information about (sufficiently) large dissimilarities which determine the global structure of MDS solutions. To provide complementary evidence about the finer structure among adjacent stimuli, a second matrix DISS_S was included in the same analysis, consisting of MijS values treated as dissimilarities--but only for those stimulus pairs where the MijD value was rejected, with [missing data] entries otherwise . dissim_sij=MSijif fraction ofSresponses>66%=missingdataotherwise It follows from the filtering rule that if a stimulus pair (i,j) is represented by its MijD value in a filtered SIM_D matrix, while another pair (k,l) is omitted there but is represented by its MklS value in the corresponding DISS_S matrix, then (k,l) is more similar than (i,j). We emphasize that the MDS analysis below does not use this inference in any way. RT-derived MDS solutions Following accuracy-based analysis in Bimler et al. (2013), we retained four-dimensional MDS solutions for the MO and WF series separately, for each presentation mode, using an implementation of Kruskal's algorithm in its multiple-matrix repeated-measures mode to pool two subjects' SIM_D and two DISS_S matrices for each poser. Notably, and unexpectedly, no systematic inversion-related differences appeared between solutions for the U and I data, so they are superimposed in Figure 7 as two sets of points, using Procrustes analysis (Gower, 1975) to rotate each pair of solutions to the closest congruence. Given this similarity, we pooled the U and I data to obtain consensus MO and WF solutions (not shown). Values of Stress1 for the 2D to 4D solutions were 0.144, 0.105, 0.088 (MO) and 0.178, 0.126, 0.101 (WF). These Stress1 values and interpretability of all four dimensions justify retention of four dimensions in both cases. After rotation, as expected, the first dimension D1 is a bipolar "Valence" axis, distinguishing the Happiness stimulus and its morphs at one extreme from negative-valence FEs at the other. The other axes are unipolar, running from "Neutral" to "Fear/Surprise" (D2), "Anger" (D3) and "Disgust" . Figure 7 Four-dimensional MDS solutions for MO (top) and WF (bottom) stimulus sets, from "filtered" RT*(i,j) medians sim_dij and diss_dij, pooling two observers for each stimulus set and superimposing solutions for Upright (*) and Inverted (#) observation (linked by lines). Projection on D1D2 (left) and D3D4 (right) planes. For confirmation we derived a dissimilarity function (dij), and created dissimilarity matrices DMO and DWF, by defining the difference between the i-th and j-th stimulus in terms of the profiles of median RTs involving them (the respective rows MikD and MjkD in the similarity matrix). Specifically, dij is the Euclidean distance between rows MikD and MjkD : dij=kMDik-MDjk2 whereijk . Note that in contrast with the original RT data, this dissimilarity function dij is a monotonic function of the reconstructed distances. Four-dimensional MDS solutions for the MO and WF series (each pooling the matrices for two participants and the two presentation modes) had Stress1 of 0.134 and 0.141, respectively, and were encouragingly similar to those obtained above. Comparison of solutions derived from RTs and accuracy rates These combined RT-derived solutions were compared to the solutions extracted from the accuracy-rate data (Bimler et al., 2013). Similarity between MDS solutions derived from the two behavioral measures was quantified in several ways. One is the Procrustes statistic R2, measuring the total sum of residual distances between corresponding points that remain when the configurations have been rescaled, translated, reflected and rotated so as to maximize the overlap between them (Gower, 1975). A value of R2 = 0 indicates complete convergence of the two structures. In this case the values were small: R2 = 0.051 when comparing the solutions from accuracy rates and RTs for the MO series, and R2 = 0.032 for the WF series. A second form of comparison, canonical correlation (CANCORR), has the advantage of allowing significance tests in the form of Wilks' L statistic, here a very stringent test with only 15 points for the correlations. For both the MO and WF series, all four dimensions of the RT solution have recognizable counterparts in the accuracy-rate solution, with p <= 0.002 and p < 0.005, respectively. Effect of FE inversion No glaring difference between the RTs to Upright and Inverted pairs of stimuli was apparent . At a finer level of analysis, Figure 8(left) plots the D-response median RTs MijD for each pair of Inverted stimuli against MijD for the identical pair when presented Upright. In the same way Figure 8(right) plots the S-response median RTs MijS . It is apparent that inversion failed to substantially affect processing time: the points are concentrated around the diagonal. Significant variations are in the minority (before correcting for multiple comparisons). Median D RTs of participant HK were shorter for Upright pairs than for Inverted pairs by 4.8 ms, p = 0.029; in comparison, SB gave faster D and S responses to Inverted than Upright stimuli, by 21.9 and 40.9 ms, respectively, both p < 0.001. Crucially, these unsystematic within-participant differences were far smaller than differences between the observers, with DK as the fastest responder and SB as the slowest. Figure 8 Median RT*(i,j) for Upright pairs (horizontal axis) vs. Inverted pairs (vertical axis). MijD for D responses (left); MijS for S responses (right). Superimposed results for four observers. Pairs omitted if four or fewer responses in either presentation mode. A detailed comparison of 4D structures is difficult when working with 2D perspectives, where a high-dimension rotation can shift points' locations in unexpected ways. Conversely, apparent clustering of points may be coincidental overlaps. To facilitate comparison of the MDS summaries of filtered RTs, we processed the distances within each solution with hierarchical clustering analysis (HCA), specifically, mean link agglomerative algorithm. HCA results (dendrograms) for Upright and Inverted images of the MO and WF series are shown in Figure 9. HCA cannot be applied to the SIM_D and DISS_S matrices directly due to their missing-data entries. Figure 9 Dendrograms derived from MDS solutions for median RT*(i,j) for MO series (upper row) and WF series (lower row), Upright (left) and Inverted (right). If the subjective similarities represented in MDS solutions strictly follow the construction of the stimulus set, one expects clusters in the HCA that contain a pair of the prototype FEs and their intermediate morph. For instance, taking Sadness and Neutral expressions as a relatively similar pair of prototypes, where the SaN stimulus is (objectively) between at an equal distance from both, if SaN clusters with Sadness, then it should be equally similar to Neutral, drawing the latter into the cluster. The same might occur for Fear, Surprise and FSu. For the MO stimuli, as expected, both U and I solutions exhibit a cluster of Fear/Surprise/FSu, part of a high-level three-way division (ASu is a peripheral member of the cluster, but not the Anger prototype). Further, the "negative" emotions Sadness, Anger and Disgust and their morphs comprise a second cluster, joined by SaN but not Neutral, contrary to the equal-similarity assumption. Finally, the three half-Happiness morphs HN, SuH and AH have coalesced with the Happiness prototype into the third cluster. That is, the morphs were all more similar to Happiness than to their other "parent" prototypes: the response times appear to reflect a degree of categorical processing, which persists when stimuli are inverted. It is worth noting that the same features are present in hierarchical-clustering solutions for accuracy-rate similarity matrices (not shown). We observed, however, that inversion does shift some morphs from the periphery of one cluster to another. In particular, SuH and DF are both in the Fear/Surprise group according to Upright responses, but inversion shifts SuH to the Happiness cluster and DF to the "negative" cluster. Conversely, Neutral is in the Happiness cluster according to Upright responses (linked by its proximity to HN), but is in the Fear/Surprise group when inverted, where the connection is less obvious. One cannot read too much into these details, as the cluster membership of ambiguous stimuli is susceptible to random fluctuations in the data. The WF solutions, in comparison, exhibit a two-way split, distinguishing a cluster of Sadness, Disgust, Neutral and their morphs. Other stimuli are more of a continuum, affected by data fluctuations. The Happiness prototype and morphs do not coalesce completely for Inverted data, but Fear, AH and SuH do form a consistent tight cluster. Another tight cluster can be discerned in both U and I results, combining Surprise with FSu and ASu, along with Anger (drawn by proximity to ASu) but not Fear. Recall that these local details are driven by the DISS_S matrices, in contrast to the SIM_D matrices determining the global structure. Discussion Learning effect Following the outline of the Results section, we begin by addressing possible learning effect on RTs. The unusually large number of trials and responses in this study (T = 100 per stimulus pair) highlight certain important aspects of RTs. First, they vary with practice--generally becoming shorter, albeit with relapses. This will not surprise anyone who has played computer games or learned to touch-type, engraining automatic motor pathways by dint of time and practice. Importantly though, these fluctuations were not accompanied by any systematic shift in accuracy rates across the course of data collection, as assessed by the discrimination d' and bias C parameters (Bimler et al., 2013). It would seem that the improvements are limited to the motor skill of pressing one or the other key. Crucially for present purposes, RTs for specific pairs show no progressive changes over runs when rescaled to be proportional to the median RT for a given run. This learning effect is not a serious concern here because the drift affects the median RT to the same extent across stimulus pairs. However, extensive practice does increase the variance around each median, obscuring the shape of the distributions, which provides the rationale for reducing that variance with the corrections applied here. Presumably similar practice shifts also occurred, although to a lesser extent, in RT data gathered with fewer S/D trials (e.g., Takane and Sergent, 1983). Individual variation The variations among observers are of note. Even within the small group studied here, SB responded more slowly than the others with a smaller relative advantage for D responses , and a relative advantage for Inverted pairs . It may be that personality traits influence these differences in decision and, hence, dual-process parameters. For example, Nowicki and Cooley (1990) reported that subjects with internal locus of control were significantly faster to distinguish different emotions in a S/D task. Cognitive style may, also, underlie differences in an individual's strategy of attention allocation, reflected by an eye-movement pattern of exploration of the compared images that affects the process and chronometry of a perceptual decision (for a discussion cf. Bendall et al., 2016). The ex-Gaussian functions fitted to the RT data may be relevant here. The m and s parameters of the normal component characterize the "leading edge" of a distribution and are conjectured to reflect early automatic processing, whereas t, the exponential component characterizing the length of the tail, is more likely to reflect central attentional process (e.g., Balota and Spieler, 1999). As seen in Table 1, m and s are higher for SB than for other participants in both U and I modes while t is lower, i.e., distribution skewness. Moret-Tatay et al. (2016) attribute lower t to reducing either the tendency to double-check by a participant before responding or the amount of attentional lapsing. One can speculatively interpret SB's lower t as fewer attentional lapses than other participants', i.e., her "attentional-based strengthening" due to "enhancement in cognitive control" (in the authors' terms) was higher, also increasing m and s. However, as noted by Heathcote et al. (1991) and Matzke and Wagenmakers (2009), the rationale for ex-Gaussian functions is more empirical than theoretical, so we have not attempted to interpret the parameters further. The role of the ratio of different-stimulus pairs in the design Another factor that possibly affected the obtained outcome is the imbalance of (factually) different-stimulus pairs in our experimental design. The identical-stimulus pairs in the present study, 7%, were scarce compared to the default design in RT research of 50% of total trials. This aspect of the design, facilitated by the brief presentation time, might have encouraged observers to overlook points of difference (or to pay more attention to points of similarity), biasing their judgments toward erroneous S responses (cf. Krueger and Shapiro, 1981). It may be that in the absence of explicit guidance for how many "same" pairs to expect, and in the absence of corrective feedback, participants implicitly set their own targets for what seemed a plausible rate and adjusted the thresholds of their decision processes accordingly. In the dual-process framework, the present design is likely to have had an impact on the drift rate of information accrual in the dual processes (cf. Ratcliff, 1978) and, hence, the balance between them. More specifically, it seems to have elevated the critical level of stimulus disparity required for an S or D judgment to be equally likely (with observers accepting disparities below this criterion as 'sufficiently identical'), a strategy regarded by Smith et al. (2008) as characteristic of non-human primates. The predominance of different-stimulus pairs appears to have the unintended effect of increasing the number of erroneous S responses, with the benefit of enhancing the statistical robustness of false S rates when they serve as an index of stimulus similarity. As a result, we were previously able to use each subject's percentage of D responses to each stimulus pair as a yardstick of "dissimilarity" (Bimler et al., 2013). We also observed that S judgments were made more slowly than D judgments for the same-stimulus pair , although the delay varies with pair and with the participant. This may be another outcome of the change of processing criteria, in accordance with Downing's (1970) report that S responses were slower when they were less frequent (25% vs. 50% of trials). Future studies could examine the effects of variation in the proportion of different-stimulus pairs on shifting the criterion of perceptual decisions, potentially reflected by accuracy rate and mean RT difference of S and D responses. The RT function of stimulus similarity does not sustain monotonicity The outcome of the observers' relaxed criterion of "sameness" in the present study revealed a feature of the Same/Different task that normally is obscured. In particular, the data become a test of the assumption that RTs are a monotonic function of stimulus dissimilarity, assessed by accuracy ("%D"; Bimler et al., 2013) or by distances in a RT-derived MDS solution as a smoothed version, as here. As demonstrated in the Results section, in either case, despite the simplicity and intuitive appeal of the assumption, it fails for the present data. We argue, with Ratcliff (1985) and also Ratcliff et al. (2010), that this non-monotonic RT/dissimilarity relationship is in fact an inherent feature of the task, usually concealed but brought to the foreground by aspects of the present study. When the experimental design allows a non-identical stimulus pair to attract a substantial number of S responses, it becomes possible for the Same process to forestall the Different process, and thereby truncate the distribution of RTs for D responses. For relatively similar pairs, the S responses become the majority, and they are also brief (because their underlying RT function is decreasing with similarity). Thus, D responses are recorded only on the trials when the Different process happens to handle the visual information even more rapidly--probably because some unmistakable, visually salient point of difference between the stimuli "popped out" during their presentation. Non-monotonicity is a natural corollary of a dual-process decision model. We argue that it is not observed in studies where there are 50% of same-stimulus pairs with zero disparity which attract the majority of S responses, these being correct. In such cases the response threshold for the Same process arguably is higher than in the present data (or the threshold for the D response is lower). This shifts the cross-over between the two processes--the level of dissimilarity where either response to a pair is equally likely, and the D-response distribution is truncated--to a difference too small to appear in any non-identical stimulus pairs. If, as proposed above, the observers here have adjusted their decision criteria and handicapped the Different process, as it were--shifting their thresholds to increase the fraction of S responses--this would produce Figure 6 as a side-effect. Note that Podgorny and Garner (1979), who reported RTs for D responses to same-stimulus pairs, indeed found that, consistent with our prediction, these incorrect D responses were actually shorter than RTs for many different-stimulus pairs, presumably because of the Same process forestalling longer responses. The principle with which we began--that "reducing dissimilarity increases the median value of the distribution of Different RTs"--is only true in the special case that the dual processes of the decision model can operate in isolation. This account predicts that RTs for D responses will peak at the dissimilarity for which the two kinds of responses are equally common, for that observer. Inspection of the data shows this to be the case. The same argument further predicts that median RTs of S responses will also be a non-monotonic function of dissimilarity, because at larger dissimilarities where the Different process operates rapidly we only see the truncated lower tail of the S distribution, from those trials where the Same process has operated more rapidly still. As noted, this was the case for DK. Such responses are rare, however. There is an additional complication that a S response to a dissimilar pair can also occur if the observer was unable to respond promptly (due, e.g., to inattention during the 500 ms of presentation), leaving neither process with adequate information beyond a fading memory trace, and forcing a delayed and effectively random response. Consistent with this hypothesis, here RTs were generally long when subjects gave S responses for dissimilar pairs (often exceeding 1 s). Such "timed-out" trials in this scenario can also yield long D responses, but they are lost in the large majority of rapid D responses, having little impact on MijD . MDS solution derived from a corrected RT function When the non-monotonicity is recognized it can be corrected, making the data suitable for MDS. Several lines of evidence converge to validate the RT-derived MDS solutions obtained here. In particular, these solutions concur with geometric models for the same stimuli obtained previously by interpreting the accuracy rate as a dissimilarity measure (Bimler et al., 2013). Furthermore, all present RT-derived solutions are plausible with regard to both formal and explanatory MDS criteria: they have low values of badness-of-fit (Stress1); their dimensions lend themselves to straightforward interpretation as continuous affective gradients; and they are internally consistent as models of the relationships among FE stimuli (specifically, the point representing each morph is located somewhere between the points for the prototype FE "parents"). This validates the use of median RTs as a measure of perceptual difference (in particular, for probing category effects) in the more common situation where the error rate is not high enough to serve as an index of proximity. Here we concur with Wise and Cain (2000, p. 261), who summed S/D errors across subjects and across bands of stimulus pairs, to support their conclusion that "latency to discriminate shows promise as an objective measure of qualitative similarity." No effect of inversion on discrimination of facial expressions An unexpected result was that inversion of stimulus pairs had no consistent effect on response times or the relative order of RTs , despite our expectation that the emotional content of inverted FEs would require slower serial analysis of local features due to the disruption of processing configural cues, whereby distal features are integrated into a unified whole (Rossion, 2008). One obvious explanation is that, in the challenging discrimination task, the affective content was simply not involved in the S/D decisions, these being made purely on the basis of similarity of face trivial details or visually salient diagnostic features (Arnold and Lipp, 2011; Calvo and Nummenmaa, 2011; Murphy et al., 2020; Baldassi et al., 2022), and increase in contrast (in the mouth region for happiness and the eye region for fear; Psalta and Andrews, 2014) or of perceived physical similarity, with the stimuli undergoing a low-level form of comparison as abstract patterns of gray-tones and textures (cf. Bimler et al., 2013). However, there is some evidence of an effect of inversion upon RTs and accuracy rates, but this is confined to pairs of intermediate dissimilarity where the competition between the dual processes is strongest, and thus susceptible to small changes in their parameters. Comparing the Upright and Inverted RT*(i,j) mode distributions for intermediate-similarity pairs for DK indicates that this observer identified more of the sufficiently-similar pairs as D when Inverted and (erroneously) as S when upright . Responses of HK followed the same pattern, with inversion increasing the median D RT . However, this subtle difference is not consistent across observers, and for SB the effect of inversion was to increase the number of correct D responses , in addition to allowing faster responses than in Upright presentation . These pairs were outnumbered by pairs that were sufficiently similar or sufficiently dissimilar for the Same or Different process to operate without interference, and they were lost in the MDS solutions. Feature-based early extraction of FE affective meaning The weakness of any FE inversion effect is in accord with previous findings in two studies measuring response speed--one using a visual search paradigm (Lipp et al., 2009) and another on the choice of a face with the highest emotional content in a horizontally aligned pair (Baldassi et al., 2022), where both suggest a role for low-level processing of face images. Even so, the present study demonstrates partial extraction of affective information despite the brief stimulus presentation. Specifically, the "Valence" dimension is extracted early in visual processing of facial expressions, in line with previous studies using visual search (Lipp et al., 2009) or forced-choice paradigms (for a review see Calvo and Nummenmaa, 2016). As argued by Calvo and Nummenmaa (2011, p. 1758), it is possible that affective information is extracted at some point but is "only minimally used due to [it] being overshadowed by the earlier extracted, and simpler to be managed, visual saliency information, which then was retained also for later discrimination stages." This conclusion is in accord with findings in an ERP study demonstrating that an emotional expression effect is recorded as early as 120-180 ms post-stimulus (Eimer and Holmes, 2007). The exposure of 500 ms may have been too short for the processing of the configural information involved in the full decoding of affective meaning (cf. Rossion, 2014; Calvo and Nummenmaa, 2016; Murphy et al., 2020) but it was evidently long enough to extract low-level visual cues at early stages of processing face expressions, shown to be manifested in ERPs within 200 ms (Batty and Taylor, 2003; Ashley et al., 2004; Ohmann et al., 2016; Duan et al., 2022) or relatively correct affective estimates of FEs presented for 150 ms (Arnold and Lipp, 2011). A further corollary can provisionally be drawn from the Results, that some sufficiently low-level facial property distinguished Sadness, while no such property was unique to Fear or Surprise (any low-level cues being shared between those last two expressions). Early Happiness categorical perception effect Further, along with the subjective dichotomy of the expression "Valence," our results reveal an early categorical perception (CP) effect for Happiness-images (cf. Bimler and Kirkland, 2001). Although the nature of the stimulus set precludes a rigorous test of CP, the RT-based dissimilarities do display certain hallmarks of CP. In particular, some of the interpolated morphed Happiness-stimuli subjectively are not midway between their two constituent prototypes, but are displaced toward one (i.e., are harder to distinguish from it). The Anger-Happiness, Surprise-Happiness and Happiness-Neutral morphs (AH, SuH, and HN) were all closer to the Happiness prototype than to their other constituent, although the HN morph (for instance) is physically just as close to Neutral. This would be the outcome if they fell within the boundary of the Happiness category. Notably, this structure of the subset of Happiness-stimuli is present in separate MDS solutions, congruent with our previously-reported accuracy-based outcomes of this study (Bimler et al., 2013). The emerged Happiness-subsets in the RT-derived MDS solutions are in accord with outcomes of cluster analysis . In addition, it is buttressed by Fechner analysis outcomes of our accuracy data: K-means clustering revealed a H, AH, SuH, and HN cluster, for both U and I conditions and all participants (Dzhafarov and Paramei, 2010). The early emerging Happiness category concurs with the finding of the N170 component that reflects earliest manifestation of the CP effect (Qiu et al., 2017; Duan et al., 2022). The Happiness categorization effect is also visible in the hierarchical clustering extracted from Upright and Inverted RTs . The AH, SuH, and HN morphs combine with the Happiness prototype in a distinct cluster: in speeded similarity decisions, the 50% of Happiness dominates the 50% of other emotional prototypes, regardless of inversion. This early manifestation of the Happiness category concurs with both the timing of psychophysiological components--a shorter latency of the N170 (Batty and Taylor, 2003) and categorization advantage (lower discriminability) of positive expressions (Qiu et al., 2017); and, as well, of behavioral measures of responses to Happy faces--shorter visual search times (Lipp et al., 2009), saccade latencies (Calvo and Nummenmaa, 2011; Beaudry et al., 2014), and faster choices of the "happiest" than the "angriest" face in a pair (Baldassi et al., 2022). Our finding is also in accordance with the visual salience of a "smile" feature estimated using behavioral measures: Smith and Schyns (2009) and Bombari et al. (2013) found the Happiness expression to be low-spatial-frequency rich, involving the mouth as its distinguishing feature more than the other prototype FEs. Lower perceptual thresholds for Happiness detection compared with Fear, Anger or Sadness point out to the lip-end raise as a highly diagnostic feature (Calvo and Nummenmaa, 2011; Du and Martinez, 2013; Maher et al., 2014; Calvo et al., 2018). This distinctive single cue bypasses integration of face parts (cf. Calvo et al., 2014) and, in the present study, renders the categorical processing of briefly glimpsed facial Happiness, in both its "pure" and morphed forms, less susceptible to inversion. Concluding remarks The absence of difference in the RT pattern of "Same"-"Different" judgments between Upright and Inverted FE pairs suggests that the participants were viewing the (briefly presented) faces not as Gestalts but, rather, as abstract patterns of low-level features (maybe as gray-tone gradients). In the above discussion of potential information-processing mechanisms behind the present findings we favored the explanation that leans upon the dual-process model and implies separate thresholds in the Same and Different accruing processes. This explanation, though, is not the only possibility. We are grateful to an anonymous reviewer, who pointed out that this finding of no inversion effect implies that the S/D task is a search paradigm, whereby independent (low-level) stimulus components undergo an analytic and self-terminating comparison, a "feature search" or search of feature conjunctions (Farell, 1985, 2022). Our results fit into a serial search paradigm with expected shorter D responses compared to S responses. However, as pointed out by Farell (1985) in his seminal work, the relation between the pattern of "Same"-"Different" judgments and parallel vs. serial processing is difficult to determine. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics statement The studies involving human participants were reviewed and approved by Institute of Psychology, Darmstadt University of Technology, Germany. The participants provided their written informed consent to participate in this study. Author contributions DB conducted the data analysis and contributed to writing the manuscript. GP contributed to the study design, running the experiment, initial data processing, and writing the manuscript. All authors contributed to the article and approved the submitted version. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. The authors are grateful to Slawomir J. Skwarek and Sina Holtfreter (nee Willems) for indispensable assistance in data collection and Wolfgang Bosche for adapting the software for stimulus generation. Valuable advice on the experimental design from Ehtibar N. Dzhafarov and Hans Colonius is gratefully acknowledged. We thank the participants for their time, understanding and collaborative spirit. Helpful comments of two reviewers are highly appreciated. Supplementary material The Supplementary material for this article can be found online at: SUPPLEMENTARY FIGURE S1 RT* distributions, Upright and Inverted, for HK (top row), BF (middle row) and SB (bottom row). (a) S responses for 15 identical pairs; (b) D responses for 10 most-different pairs; (c) S responses for 10 intermediate-similarity pairs; (d) D responses for 10 intermediate-similarity pairs. Click here for additional data file. SUPPLEMENTARY FIGURE S2 RT*(i,j) distributions for 15 identical pairs (solid lines) with superimposed ex-Gaussian functions (dotted lines) for three remaining participants (rows), in Upright (left) and Inverted (right) modes of FE presentation. Click here for additional data file. References Arnold D. H. Lipp O. V. (2011). Discrepant integration times for upright and inverted faces. Perception 40 , 989-999. doi: 10.1068/p6955, PMID: 22132513 Ashley V. Vuilleumier P. Swick D. (2004). 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PMC10000313 | J Belg Soc Radiol J Belg Soc Radiol 2514-8281 Journal of the Belgian Society of Radiology 2514-8281 Ubiquity Press 10.5334/jbsr.3006 VoR Case Report Intracranial Arteriovenous Malformation Combined with Multiple Aneurysms Diagnosed by CTA: A Case Report Zhang Qin 1 Hou Yongzhe 1 Wang Qiong 2 Chen Xilong [email protected] 13 1 Gansu University of Traditional Chinese Medicine, CN 2 The Third People's Hospital of Bijie City, Radiology Department, CN 3 Department of PICU, Gansu Provincial Maternity and Child-Care Hospital, CN CORRESPONDING AUTHOR: Xilong Chen Gansu University of Traditional Chinese Medicine, CN [email protected] 06 3 2023 2023 107 1 1604 11 2022 13 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Arteriovenous malformation (AVM) combined with aneurysms is not uncommon, but AVM of the basilar artery, brainstem, and right middle cerebral artery combined with multiple intracranial aneurysms (IAs) is rare. Cases of aneurysm protrusion into the optic canal are also rare. We report a distinctive case of intracranial AVM combined with multiple IAs and partial protrusion of a cavernous segment aneurysm of the right internal carotid artery into the optic nerve canal. Teaching Point: Cases of partial protrusion of a cavernous segment aneurysm of the right internal carotid artery into the optic canal, resulting in widening of the optic canal compared to the contralateral side, compression, thickening and swelling of the subocular veins, and obstruction of venous drainage warrant the clinician's attention. arteriovenous malformation aneurysm computed tomography angiography intracranial cerebral Education Department of Gansu Province 10.13039/501100009590 lccx2021001 The 2022 project of innovation foundation of outstanding graduate students of Gansu Province; the graduate innovation foundation of major project of Education Department of Gansu Province, No. lccx2021001. pmcIntroduction Intracranial arteriovenous malformation (AVM) combined with multiple intracranial aneurysms (IAs) is a complicated and specific cerebrovascular disease, with an incidence ranging from 2.7% to 16.7% and is a common risk factor for hemorrhage, with a high mortality rate . Case History A 57-year-old man was rushed to the emergency room with intermittent convulsions. The patient had a five-year history of hypertension and a single seizure one year earlier. Axial computed tomography angiography (CTA) image showed a vascular mass (red arrow) and thickened, swollen inferior ophthalmic vein (white arrow). The bone window axial CTA image demonstrated a right internal cavernous sinus aneurysm locally protruding into the optic canal (red arrow) and optic canal enlargement compared to the contralateral side (white arrow). A basilar artery aneurysm was present . Multiplanar reformation sagittal image shows saccular aneurysm (red arrow) approximately 2.4 cm x 1.3 cm in size with a narrow neck originating from the cavernous segment of the right internal carotid artery. The bone window coronal CTA image demonstrates the feeding artery (white arrow) and the malformed vascular mass (red arrow), while the volume rendering illustrates the draining vein (white arrow) and the basilar artery aneurysm (red arrow). Figure 1 CTA presentation of intracranial arteriovenous malformation combined with multiple aneurysms. CTA presentation of intracranial arteriovenous malformation combined with multiple aneurysms The final diagnosis was intracranial AVM combined with multiple IAs and a right internal carotid artery aneurysm. The patient was given antiepileptic, vasospasm-relieving, and blood pressure-controlling medication after being admitted to the hospital. When the patient had stabilized, the patient was transferred to another hospital. However, due to financial constraints, the patient and his family declined the further therapy and were self-discharged from the hospital. Comments The mechanism of AVM combined with IA is complicated. IA mostly occurs in the supplying arteries of AVM and there is a blood flow correlation between IA and AVM. Moreover, fibrous degeneration and thinning of the AVM-supplying arterial walls, disruption of the intima, and alterations in the vascular musculature lead to a significant increase in pressure in the AVM-supplying vessel. These hemodynamic mechanisms may explain the development of AVM combined with IA. Given the patient's imaging data, this case of AVM combined with IA is difficult to handle because of the following characteristics: IA occurred in the supplying artery of the AVM, which is different from the vascular structure of an ordinary IA and is clinically rare. Besides the IA in the intracranial arteriovenous malformation mass, IA was also present in the distal basilar artery and the right internal carotid artery. The IA of the cavernous segment of the right internal carotid artery partially protruded into the optic canal, resulting in widening of the optic canal compared to the contralateral side and compression, thickening, and swelling of the inferior ophthalmic vein by obstruction of venous outflow. The arteriovenous malformation vascular mass was supplied by the C5-6 segment of the internal carotid artery and the basilar artery, and several drainage veins were seen converging into the superior sagittal sinus. And IA predominantly occurred in vessels other than ordinary IA vessels (e.g., anterior and posterior communicating arteries). Digital subtraction angiography (DSA), which is the gold standard for the clinical diagnosis of AVM and IA, its use is restricted because it is an invasive examination and more likely to cause cerebrovascular accidents than CTA (e.g., aneurysm rupture and transient cerebral ischemia due to vasospasm). However, because CTA is a noninvasive, inexpensive, and quick imaging technique, it can be utilized as a reliable alternative to DSA in emergencies demanding immediate operation . CTA and its multiple reconstruction modalities (e.g., volume rendering, maximal-intensity projection, multiplane reconstruction) are of great value in the diagnosis of AVM and IA. The clinical significance of CTA is that it can reveal the blood supply arteries and drainage veins of AVM, as well as the location, size, morphology, thrombi, and calcification of AVM, allowing physicians to more precisely assess AVM and IA. CTA may also display the architecture of the lesion and its relationship with neighboring tissues in numerous angles and planes. Additionally, the CTA technique can save examination time, accurately localize bleeding, and help with disease characterization when acute rupture of IA occurs, guiding the development of treatment plans. Furthermore, patients prefer to select less expensive CTA in some poor areas of developing countries. Therefore, diagnoses of AVM combined with IA can be made using CTA as an alternate imaging technique to DSA. Conclusion We reported a rare case of intracranial AVM combined with multiple IAs and partial protrusion of a cavernous segment aneurysm of the right internal carotid artery into the optic nerve canal, to increase awareness of this rare cerebrovascular disease. Funding Information The 2022 project of innovation foundation of outstanding graduate students of Gansu Province; the graduate innovation foundation of major project of Education Department of Gansu Province, No. lccx2021001. Competing Interests The authors have no competing interests to declare. 1 Jha V, Behari S, Jaiswal AK, Bhaisora KS, Shende YP, Phadke RV. The 'focus on aneurysm' principle: Classification and surgical principles of management of concurrent arterial aneurysm with arteriovenous malformation causing intracranial hemorrhage. Asian J Neurosurg. 2016; 11 (03 ): 240-254. DOI: 10.4103/1793-5482.145340 27366251 2 Kouskouras C, Charitanti A, Giavroglou C, et al. Intracranial aneurysms: Evaluation using CTA and MRA. Correlation with DSA and intraoperative findings. Neuroradiology. 2004; 46 (10 ): 842-850. PMID: 15448952. DOI: 10.1007/s00234-004-1259-2 15448952 |
PMC10000314 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1213 VoR Multimodality Museum Image Atypical Left Ventricular False Chordae Tendineae Darwish Amr MD [email protected] 1 Wessly Priscilla MD 1 Faza Nadeen MD 1 1 Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US CORRESPONDING AUTHOR: Amr Darwish, MD Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 100102 01 2 2023 03 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See An 81-year-old female patient with a history of severe secondary mitral regurgitation, hypertension, and paroxysmal atrial fibrillation was seen by the valve team to determine candidacy for transcatheter edge-to-edge repair of the mitral valve. Two-dimensional biplane imaging showed a transverse basal left ventricle false tendon attached to papillary muscles. The position was concerning for interference during deployment of the mitral clip. LV false tendon chordae tendineae LV false chord 3-dimensional transesophageal echocardiography mitraclip pmcLeft ventricular false chordae tendineae are fibromuscular structures in the ventricular cavity without connection to mitral valve leaflets. Although first described more than 100 years ago, the pathophysiological significance of these structures remains unclear.1 Some studies have suggested that false tendons reduce the severity of functional mitral regurgitation by stabilizing the position of the papillary muscles as the left ventricle enlarges.2 Transverse false tendons also are associated with early repolarization, which could be a substrate for ventricular arrythmias.3 Figure 1 and Videos 1-3 show cardiac images of an 81-year-old female patient with a history of severe secondary mitral regurgitation, hypertension, and paroxysmal atrial fibrillation. She was seen by the valve team to determine candidacy for transcatheter edge-to-edge repair of the mitral valve. Two-dimensional biplane imaging showed a transverse (localized to one zone) basal left ventricle (LV) false tendon attached to papillary muscles. The position was concerning for interference during deployment of the mitral clip. Video 1 Two-dimensional biplane transesophageal echocardiography, two chamber mid-esophageal view, showing transverse chord-like structure close to mitral valve connecting the papillary muscles; see also at Video 2 Three-dimensional transesophageal echocardiography showing atypical left ventricular false tendon; see also at Video 3 Two-dimensional transesophageal echocardiography showing successful MitraClip implantation with residual mitral regurgitation and the tendon remained intact; see also at Figure 1 (A) Two-dimensional transesophageal echocardiography (TEE) (mid-esophageal 2-chamber view) shows a transverse chord-like structure (blue arrow) connecting the papillary muscles. (B) Three-dimensional TEE of the mitral valve highlights the transverse tendon (blue arrow). The procedure was successful with (C) residual mild mitral regurgitation, and (D) the tendon remained intact. LA: left atrium; LV: left ventricle. 2D and 3D TEE imaging of a transverse basal LV false tendon during MitraClip implantation Competing Interests The authors have no competing interests to declare. 1 Silbiger JJ. Left ventricular false tendons: anatomic, echocardiographic, and pathophysiologic insights. J Am Soc Echocardiogr. 2013 Jun;26 (6 ):582-8. doi: 10.1016/j.echo.2013.03.005 23602169 2 Bhatt MR, Alfonso CE, Bhatt AM, et al. Effects and mechanisms of left ventricular false tendons on functional mitral regurgitation in patients with severe cardiomyopathy. J Thorac Cardiovasc Surg. 2009 Nov;138 (5 ):1123-8. doi: 10.1016/j.jtcvs.2008.10.056 19660373 3 Liu Y, Mi N, Zhou Y, et al. Transverse false tendons in the left ventricular cavity are associated with early repolarization. PLoS One. 2015 May 1;10 (5 ):e0125173. doi: 10.1371/journal.pone.0125173 25933440 |
PMC10000315 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1177 VoR Review Houston Methodist Ruptured Abdominal Aortic Aneurysm Guidelines Dang Vy C. MD [email protected] 1 Osztrogonacz Peter J. MD 2 Haddad Paul MD 2 Sharma Shashank MD 2 Corr Stuart J. PhD 2345 Rahimi Maham MD, PhD 2 1 Texas A&M School of Medicine, Bryan, Texas, US 2 Houston Methodist Hospital, Houston, Texas, US 3 Rice University, Houston, Texas, US 4 Swansea University Medical School, Swansea, United Kingdom 5 Weill Cornell Medical College, New York, New York, US CORRESPONDING AUTHOR: Vy C. Dang Texas A&M School of Medicine, Bryan, Texas, US [email protected] 07 3 2023 2023 19 2 7889 21 10 2022 07 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Ruptured abdominal aortic aneurysm (RAAA) is an acute aortic condition that requires emergent intervention and appropriate continuity of care to optimize patient outcomes. We describe the standardized RAAA protocol at the Houston Methodist Hospital Acute Aortic Treatment Center, developed to navigate critical patient transfer periods safely and efficiently, make crucial decisions about surgical intervention, and clearly communicate these plans with other care team providers. Our workflow is organized into five phases: prehospital, preoperative, intraoperative, postoperative, and post-discharge. We identify the transfer center, anesthesia, operating room nursing staff, surgeons, and intensive care unit as key entities of our acute aortic pathology care team. This systematic protocol for the management of acute aortic emergencies such as RAAA identifies critical decision points, potential complications at each stage, and recommendations for best practice. ruptured abdominal aortic aneurysm transfer of care RAAA Timeout patient outcomes protocol guidelines acute aortic syndromes THROMBINS2 pmcIntroduction Ruptured abdominal aortic aneurysm (RAAA) is an acute aortic condition that requires immediate action and appropriate continuity of care to optimize patient outcomes. The decline in the number of RAAAs in the United States (US), along with the innate fast-paced nature of aortic emergencies, has left fewer opportunities for the medical team--emergency room personnel, nurses, anesthesiologists, fellows, residents, surgeons, and critical care physicians--to improve and maintain their skillset for RAAA management.1 Consequently, a systematic standardized protocol-driven approach is essential to improve the management of aortic emergencies as well as perioperative morbidity, mortality, and long-term survival. Although current Society of Vascular Surgery (SVS) Guidelines provide recommendations for the perioperative management of RAAA,2 aortic centers with lower volumes of RAAA cases require a robust, standardized protocol applicable to their specific needs. In this article, we summarize the internal protocol of the Houston Methodist Hospital (HMH) Acute Aortic Treatment Center (AATC) to provide guidance to vascular surgeons in training and to low-volume aortic centers, guided by the five phases of surgical care outlined by the American College of Surgeons (ACS): preoperative, perioperative, intraoperative, postoperative, and post-discharge. Preoperative Phase Transferring Process Before the patient arrives from a transferring hospital or emergency room, a general call should be initiated. The transferring hospital should provide the patient's name, date of birth, medical record number, reason for transfer, code status, the presence/absence of metastatic cancer, and anticoagulants. The receiving hospital should provide instructions for transfer, including a reminder to maintain permissive hypotension and avoid intubation and sedation, if possible. After 5 minutes, another call should take place. We recommend the development and utilization of an efficient, HIPAA-compliant alert system that reaches the surgeon, anesthesiologists, operating room (OR) staff, and intensive care unit (ICU) staff for rapid transfer of information. This alert should include the current vitals, fluids, pressors, or other drugs administered, the patient level of consciousness, whether they are actively undergoing cardiopulmonary resuscitation, patient code status, and the patient transfer destination and time frame.3 The alert system may be cloud-based and allow for sharing of computerized tomography angiogram (CTA) images from the initial diagnostic workup. At the HMH AATC, we use Life Image(r) and are transitioning to Ambra(r), a cloud-based medical image management system. The hybrid OR should be prepared for patient transfer and operation. All patients with RAAA accepted for transfer should be transferred directly to the hybrid OR. A blood type and screen should be performed in the receiving hospital, if not already done, but should not delay transfer. The transferring hospital should be instructed to avoid intubation and sedation, if possible. Intravenous (IV) access should be obtained via two large-bore peripheral lines.2,3 Fluid resuscitation introduces a risk of coagulopathy, hypothermia, and acidosis and thus should be avoided if the patient is conscious. If necessary, the patient may receive balanced transfusion (1:1:1 packed red blood cells:fresh frozen plasma:platelets). If the patient requires resuscitation, the goal is to achieve permissive hypotension, defined as maintaining patient consciousness and systolic blood pressure (SBP) between 70 mm Hg and 90 mm Hg through the conservative delivery of IV crystalloids/colloids to prevent major blood loss during the operation.3 Permissive hypotension and controlled hypotension, which is the lowering of blood pressure with vasodilators and/or beta blockers, are two approaches to maintaining SBP between 50 mm Hg and 100 mm Hg and achieving hypotensive hemostasis.4 However, because of patient variability and the risks of prolonged and severe hypotension (ie, mesenteric ischemia, acute kidney injury), we prefer to use permissive hypotension as our guide in resuscitation at the HMH AATC. Remote Patient Evaluation by Surgeon The surgeon must first determine whether proximal control is necessary and what method is optimal, be it percutaneous endovascular balloon control (EVBC) or aortic cross-clamping through an abdominal midline incision. EVBC is performed under local anesthesia and recommended for hemodynamically unstable patients and/or those unresponsive to fluids and drugs.5,6,7,8 Hemodynamic stability is defined in these guidelines as consciousness with no fluid or pressors to maintain blood pressure between 70 mm Hg and 90 mm Hg for at least 5 minutes. Additionally, supraceliac aorta free of aneurysmal or major atherosclerotic disease and an adequate length of healthy aortic segment is necessary to safely perform balloon control. EVBC can be followed by either endovascular aortic repair (EVAR) or open surgical repair (OSR), while aortic cross-clamping necessitates OSR. Figure 1 Algorithm for preoperative blood pressure and volume management. Hemodynamic stability is defined as patient consciousness with no fluid/pressors to maintain blood pressure between 70-90 mm Hg for at least 5 minutes. BP: blood pressure; EVAR: endovascular aortic repair; EVBC: endovascular balloon control; OSR: open surgical repair; SBP: systolic blood pressure. Algorithm for preoperative blood pressure and volume management. Hemodynamic stability is defined as patient consciousness with no fluid/pressors to maintain blood pressure between 70-90 mm Hg for at least 5 minutes. BP: blood pressure; EVAR: endovascular aortic repair; EVBC: endovascular balloon control; OSR: open surgical repair; SBP: systolic blood pressure The surgeon should have approximately 30 minutes during the transfer period to plan the procedure using 3-dimensional modeling software, such as Siemens Syngo.via(r), OsirixTM, 3Mensio Vascular(r), or TeraRecon, to evaluate whether the patient will undergo EVAR or OSR.9 SVS Guidelines recommend EVAR whenever patient anatomy allows for it.2 CTA findings indicating the utility of EVAR include sufficient diameters of femoral and iliac arteries without excessive tortuosity or calcifications, an aortic bifurcation diameter of at least 17 mm, and sufficient diameter, angle, and length of the aneurysmal neck (>= 15 mm) (Table 1).2,4 Inability to perform EVAR due to access-related issues can be remedied with either open exposure of the common femoral artery or iliac conduits. If EVAR is appropriate, the radiology technician should be alerted. Table 1 Important computerized tomography angiogram findings prior to treatment of RAAA.2,4 EVAR: endovascular aortic repair; OSR: open surgical repair; AAA: abdominal aortic aneurysm; RAAA: ruptured abdominal aortic aneurysm EVAR OSR OTHER CONSIDERATIONS REGARDLESS OF EVAR OR OSR Diameter (< 32 mm), angle (< 60deg) and length (>= 10 mm depending on type of endograft) of aneurysmal neck Extent of healthy artery free of calcifications and aneurysms Superior mesenteric artery: level of aortic origin, presence of stenosis/obstruction Diameter of aortic bifurcation (>= 17 mm) Distal disease Diameter of common iliac arteries (>= 5 mm) Free vs contained RAAA Diameter of external iliac arteries (>= 5 mm) Presence of retro-aortic left renal vein Diameter of femoral arteries without excessive tortuosity or calcifications (access point) Thoracoabdominal aneurysm, inflammatory AAA, horseshoe kidneys RAAA patients with aortic anatomy unsuitable for EVAR should be treated with OSR. Preoperative planning for OSR includes decision-making between transperitoneal versus retroperitoneal approaches, assessment of the proximal and distal clamping zones, the presence of retroaortic or circumaortic left renal vein, and the evaluation of visceral circulation (Table 1).2,3,4 Although the transperitoneal supraceliac approach is considered the gold standard exposure, an alternative retroperitoneal exposure is required for multiple recent prior abdominal surgeries, horseshoe kidney, inflammatory aneurysm, or the presence of thoracoabdominal aneurysm. The preoperative assessment of CTA to evaluate proximal and distal clamping sites helps to avoid calcified or aneurysmal aorta and/or iliac arteries. Excessive bleeding due to left renal vein injury can be avoided by identifying the aberrant left renal vein course on the preoperative CTA, contributing to improved perioperative mortality. Finally, evaluation of the visceral circulation is considered one of the most important steps of preoperative planning to avoid postoperative mesenteric ischemia. The perioperative CTA should be evaluated carefully to assess the degree of superior mesenteric artery (SMA) disease, evidence of prior hemicolectomy (especially involving the transverse colon), absence of middle colic artery, and/or the patency of the inferior mesenteric artery (IMA). In addition to the previous CTA findings, the IMA back bleeding and Doppler evaluation of small and large bowel during OSR should guide consideration for SMA intervention versus IMA reimplantation. The surgeon should be prepared for open surgical conversion during the EVAR procedure; thus we cannot stress enough how crucial the preoperative anatomical evaluation is in both OSR and EVAR. Intraoperative Phase RAAA Timeout As soon as the RAAA patient arrives at the OR, the vascular surgeon and anesthesiologist should have a focused conversation with the transferring personnel regarding the patient's hemodynamic status during transfer and the type, dose, and exact time of administered drugs, crystalloids, colloids, and blood products. Patient handoff is an especially crucial moment in the management of RAAA, as the treating medical staff must be aware of prior therapy to make an informed hemodynamic assessment. In our institution, this conversation is called "RAAA Timeout" and plays a central role in the assessment of hemodynamic status. The RAAA Timeout begins with the vascular surgeon asking the transferring personnel the following questions: Was there hemodynamic instability during transfer ? Were any pressors given during transfer? Were any crystalloids/colloids/blood products given during transfer? Then the surgeon assesses the patient's consciousness level. These focused evaluations determine the necessity of EVBC. The preoperative CTA determines OSR versus EVAR. During either procedure, the surgeon should be prepared for EVBC if the patient becomes hemodynamically unstable. Nursing The OR nursing staff should prepare either an EVAR or OSR preference cart based on the preoperative planning after the type of repair is communicated clearly by the attending vascular surgeon. A standardized workflow should be followed, including placement of a Foley catheter, prepping of the patient, checking the room temperature, placement of Zoll pads, preparation of the cell saver device, and preparation of a crash cart in anticipation of a code blue scenario. If the patient is to receive general anesthesia, they should be fully prepped and draped for balloon control prior to induction. The patient should be prepped from the nipples to knees in the supine position, with the right arm tucked and left arm on an arm board. Anesthesia Resuscitation should follow the principles of permissive hypotension as detailed in the preoperative phase, and balanced transfusion is recommended. Thromboelastography, or pulse pressure variation (PPV) in mechanically ventilated patients, may replace Swan-Ganz catheters in providing information about fluid status to guide resuscitation. If PPV < 11%, the patient has received an appropriate amount of fluid, but if PPV > 11%, more fluid is required to maintain optimal end organ perfusion.10 Obtaining venous access, placement of an arterial line, EVBC positioning, and percutaneous EVAR procedures can be completed under local anesthesia. OSR is performed under general anesthesia, with opioid administration via (1) continuous infusion of remifentanil for more stable pain control in EVAR/shorter procedures, or (2) bolus injections of fentanyl-midazolam for OSR/longer procedures.11 Patient core body temperature should be kept above 36degC; failure to do so is associated with increased perioperative morbidity and mortality.4 Ideally, EVBC and/or EVAR should be performed under local anesthesia to mitigate the detrimental impact of general anesthesia on hemodynamics. If intubation is necessary, vasoplegia and myorelaxation should be avoided to prevent hemodynamic collapse. Potential cardiovascular complications include a myocardial infarction (MI), which should be assessed and managed intraoperatively with a 12-lead electrocardiogram and transesophageal echocardiogram, and hypotension associated with ischemic reperfusion and unclamping of the aorta. Anesthesia should be prepared to administer fluid or pressors at the time of unclamping. Surgeon The vascular surgeon must be prepared for hemodynamic instability during patient intubation and must react accordingly, either by performing EVBC or supraceliac cross clamping. We recommend performing EVBC from the side of the straightest iliac system since, during the EVAR procedure, the cannulation of the contralateral limb is done through the straightest iliac.4 The balloon is ideally placed above the renal arteries if the aorta is normal and free of disease, and the time elapsed should be recorded to avoid liver and reno-visceral ischemia. In aortic cross clamping, we prefer obtaining supraceliac over infrarenal control given that the supraceliac approach is usually more readily attainable in RAAA patients. Heparin should be administered after proximal aortic control; we recommend adjusting the dose in accordance with activated clotting time. Bleeding from the proximal anastomosis may be prevented with complete transection of the aorta for end-to-end anastomosis, which makes it possible to visualize the back wall and place repair sutures. Distal bleeding, most often associated with venous injury due to complete dissection of the posterior wall of the aortic bifurcation or iliac arteries, can be prevented by the following techniques. If anastomosis is done at the aortic bifurcation, only partial transection of the aorta is favorable to prevent venous injury. If anastomosis is done at the common iliac artery, avoiding posterior wall dissection is favorable, with only anterolateral and medial control of the artery for clamp placement to avoid venous injury. If venous injury occurs, packing and pressure often stop the bleeding since attempts to repair the vein will cause further tearing. If packing does not stop a venous bleed, an assistant should help with proximal-distal control with two sponge sticks and cell-saver suction. This can often provide appropriate visualization for venous repair. If venous injury is located posterior to any aortic or iliac dissection and the bleeding does not stop with packing and pressure, complete transection of the aorta and/or iliac arteries is important for appropriate visualization and potential repair of the venous injury. Suprarenal or supraceliac posterior aortic bleeding due to clamp injury or right-angle injury to the lumbar or intercostal arteries is inaccessible to visualization and surgical repair. These types of injuries can be controlled by wrapping that level of the aorta with an Evarrest(r) Fibrin Sealant Patch circumferentially and tightly suturing the patch anteriorly to control aortic bleeding. The retracted intercostal or lumbar arteries will eventually thrombose because they are almost impossible to locate and suture-ligate. The surgeon should also take time to suture-ligate lumbar arteries prior to aortic anastomosis. Recognizing the reasons behind anastomotic bleeding is paramount prior to repair. Anastomotic bleeding can develop in several ways: a loose suture line, development of pleat, an aortic tear, suturing a heavily calcified aortic wall without incorporation of adventitia, or coagulopathy. Loose suture lines can be addressed by pulling up on the prolene suture using a nerve hook to tighten the loose suture. This loop of prolene suture is then tied down to an adjacent, newly placed prolene suture either with a surgeon instrument tie or passing a 3-0 silk suture through the loop and performing a basic surgical knot. If the surgeon initially traveled too far apart and caused a pleat formation, a figure-eight prolene suture can fix the problem. If there is an aortic tear at the anastomotic site, it can be repaired by a figure-eight parallel to the graft, suturing only the aorta. If the anastomotic bleed is due to aortic calcification, it is most likely caused by failing to incorporate aortic adventitia. The sutures should be redone at that level, incorporating the adventitia and graft using prolene sutures. For fragile aortic tissue, we recommend pledget reinforcement for figure-eight repair sutures or an external strip of Teflon felt to incorporate into the entire anastomosis (similarly used in OSR of aortic dissection).12 Postoperative Phase Early Complications in the ICU Patients should be sent to the ICU postoperatively, as complications may arise in multiple organ systems and must be carefully monitored and appropriately managed as early as possible to avoid end-organ damage and/or death (Table 2). Table 2 Postoperative complications of ruptured abdominal aortic aneurysm repair and treatment recommendations.4,12,13,14,15,16,17,18,19,20,21,22,23,24 BNP: brain natriuretic peptide; BUN: blood urea nitrogen; CBC: complete blood count; CT: computed tomography; CSF: cerebrospinal fluid; CXR: chest X-ray; ECG: electrocardiogram; ESRD: end-stage renal disease; FiO2: fraction of inspired oxygen; HLA: human leukocyte antigen; IAP: intra-abdominal pressure; INR: international normalized ratio; IMA: inferior mesenteric artery; IVC: inferior vena cava; LMWH: low-molecular weight heparin; MAP: mean arterial pressure; PaO2: arterial partial pressure of oxygen; PEEP: positive end-expiratory pressure; PCR: polymerase chain reaction; PT: prothrombin time; PTT: partial thromboplastin time; SMA: superior mesenteric artery; SSEP: somatosensory evoked potentials; SQ: subcutaneous; tcMEP: transcranial motor evoked potentials; TEG: thromboelastography; THROMBINS2: thienopyridines, renin-angiotensin system blockade, oxygen, morphine, beta-blockers, invasive cardiac interventions, nitroglycerin, statin/salicylate; VV ECMO: veno-venous extracorporeal membrane oxygenation ORGAN/SYSTEM COMPLICATION PRESENTATION/MONITOR PREVENTION TREATMENT Central nervous system Spinal cord ischemia4,12 Neurological symptoms, spinal cord (neurophysiologic) monitoring: SSEP and tcMEP, CSF drain monitoring, BP, oxygenation Avoid sustained hypotension: intraoperative MAP > 80 mm Hg Increase MAP using IV fluid bolus up to 2 L, vasopressors, inotropes. Spinal drain, increase hemoglobin, oxygenation. Cardiovascular Cardiac dysfunction4,14,15 ECG, echocardiograms, serum troponin, serum BNP, lactate Avoid volume overload (give furosemide post-op day 3 if necessary). Avoid tachycardia. Intraoperative communication with anesthesia during reperfusion to avoid excessive ischemic reperfusion injury. Practice THROMBINS2 Bleeding CBC (hemoglobin, platelet), fibrinogen, INR/PT/PTT, calcium, TEG, BUN Correct coagulopathy early. Address surgical bleed early. Appropriate surgical technique (avoid venous injury) prior to heparinization. Avoid hemodilution. Avoid excessive/prolonged heparinization. If surgical bleeding, need early mobilization to OR prior to the patient becoming coagulopathic. With bleeding patient, practice balanced transfusion. For ESRD patients, give desmopressin. Deep venous thrombosis4,16,17 Lower/upper extremity swelling, D-dimer, venous ultrasound Early mobilization, intermittent pneumatic compression, subcutaneous heparin/LMWH, removal of central access catheters, when possible. DVT prophylaxis (after successful repair and stable hemoglobin for 24 h). Heparin/LMWH (SQ), Fondaparinux (SQ), warfarin. If unable to anticoagulate, place IVC filter. Access complication Limb ischemia due to access site/limb thrombosis, groin complications (seroma, hematoma, infection), which can be associated with drainage, erythema, wound dehiscence Hourly neurovascular assessment for signs of ischemia, daily assessment for wound complication Recognize the access site complication and address it in a timely manner by returning to the OR. Pulmonary Transfusion-associated cardiogenic overload18 Elevated serum BNP, acute/worsening pulmonary edema, cyanosis, hypoxia with absence of other specific causes, unexplained cardiovascular changes Slower infusion rate, preemptive diuretics Diuretics Transfusion-related acute lung injury18 Increased oxygen demand, pink/frothy secretions from endotracheal tube, fever, hypotension, cyanosis Donor screening/deferral for anti-HLA antibodies Supportive treatment Ventilator-associated pneumonia 4,21,22 Development within 48 hours of endotracheal intubation. Respiratory decline, lung infiltrates (CXR), fever, cough. Blood cultures, sputum cultures, PCR testing from nasal swabs. Elevation of head of the bed 30-45deg to prevent aspiration. Oral chlorhexidine. Oral care, hospital hygiene measures (handwashing), timely vaccinations for patients and providers. Reduce number of days on mechanical ventilation. Empiric antibiotic therapy based on institution-specific antibiogram. Acute respiratory distress Syndrome4,18,19,20,23,24 Lung injury onset within 1 week of clinical insult, with symptoms unexplained by cardiac failure or fluid overload. Bilateral, diffuse opacities (CXR/CT). Respiratory failure. Severe hypoxemia. Decreased PaO2/FiO2 ratio (<= 300 mm Hg). On mechanical ventilation, maintain low tidal volume (<= 6 mL/kg predicted body weight). Limit blood transfusion. Reduce number of days on mechanical ventilation. Noninvasive positive pressure ventilation, low plateau pressures (< 30 cm H2O), permissive hypercapnia, appropriate titration of PEEP (>= 5 cm H2O), prone ventilation. Continuous IV infusion of neuromuscular blockers. Discuss VV ECMO. Gastrointestinal Abdominal compartment syndrome4 Difficulty ventilating patient, sustained IAP >= 20 mm Hg while patient is paralyzed. Preemptive diuretics; assess for hemorrhage. Decompression laparotomy. Diuretics, dialysis/hemofiltration, intravenous paralytic agents. Ischemic colitis4 Abdominal distension and/or pain, fevers, and early bowel movements (post-op day 0/1). Leukocytosis. Persistent acidosis. Diagnose with emergent Flex Sig. Avoid strong vasoconstrictors (ie, vasopressin or phenylephrine). Revascularize IMA or diseased SMA. Early recognition by early Flex Sig. Exploratory laparotomy with possible bowel resection. Supportive therapy (fluids, BP support, bowel rest, antibiotics, NG tube). Renal Acute kidney injury4 FENa > 1%, muddy brown casts in urine sediment, low urine output, anasarca. Minimize vasopressors, avoid prolonged suprarenal aortic cross-clamping, avoid nephrotoxic drugs Renal replacement therapies (ie, dialysis) Musculoskeletal Lower extremity ischemia Physical exam and noninvasive vascular studies. Intraoperative heparin Therapeutic anticoagulation, thrombectomy, fasciotomies for extremity compartment syndrome. The onset of neurological symptoms after an RAAA repair may indicate spinal cord ischemia during the thoracoabdominal aneurysm repair, which can be detected intraoperatively through neurophysiologic monitoring, somatosensory evoked potentials, and transcranial motor evoked potentials, to guide supportive treatment.13 However, spinal cord ischemia can be prevented intraoperatively by avoiding sustained hypotension and maintaining MAP above 80 mm Hg, in addition to postoperative monitoring of cerebral spinal fluid drain status (if one is placed), oxygen delivery (oxygen saturation and hemoglobin levels), and patient status (blood pressure, perfusion pressure, and cognitive status).4,14 Common cardiovascular complications include cardiac dysfunction and coagulopathies, all of which require clear communication and cooperation between the surgery and anesthesia to achieve the crucial balance between bleeding and thrombosis. Upon diagnosis of cardiac dysfunction, THROMBINS2 (thienopyridines, renin-angiotensin system blockade, oxygen, morphine, beta-blockers, invasive cardiac interventions, nitroglycerin, statin/salicylate) should guide the treatment plan. THROMBINS2 is a new approach developed by Advanced Cardiovascular Life Support that replaces MONA (morphine, oxygen, nitroglycerin, and aspirin) for the management of acute coronary syndromes.15,16 Bleeding should constantly be monitored and addressed early, prior to the patient becoming coagulopathic. Surgical management of bleeding is discussed in detail in the intraoperative phase. Deep venous thrombosis (DVT) is preventable with multiple techniques such as early mobilization, intermittent pneumatic compression, subcutaneous heparin and low molecular weight heparin, and removal of central access catheters, when possible.17,18 DVT prophylaxis should begin after a successful RAAA repair and after the patient hemoglobin has been stable for 24 hours. Another complication associated with RAAA treatment is based on access site complications. In EVAR or OSR, the access site complication could be due to ischemia, seroma, hematoma, and/or infection. Daily assessment of groin incisions is recommended for early recognition of these complications and addressing them in a timely manner in the OR for favorable outcomes. Lower extremity ischemia after EVAR could be due to a kink in the iliac limb of the stent graft due to iliac tortuosity, small aortic bifurcation (< 17 mm), and/or poor outflow. Furthermore, lower extremity ischemia after OSR is most often due to iliac flow-limiting dissection from clamping, poor outflow due to severe atherosclerotic disease in iliac/femoral arteries, and/or iliac graft kinking. In the era of endovascular therapy, surgeons should consider an alternate plan if the patient returns with proximal anastomosis suture line disruption with bleeding that requires endovascular salvage. The possibility of the patient returning with a suture line disruption guides the surgeon's modification of the graft during RAAA OSR, as the aortic portion of the OSR graft must fit the stent graft used in endovascular salvage. It is important, however, to not make the aortic portion of the graft too long during OSR because it may lead to iliac kinking, resulting in limb thrombosis. Lower extremity ischemia can be assessed based on physical exam and noninvasive vascular studies (ie, Doppler ultrasound) and prevented with intraoperative heparin. If detected, the patient may begin therapeutic anticoagulation, undergo thrombectomy, or require fasciotomies if extremity compartment syndrome develops. Other access site complications might be due to seroma, hematoma, and/or infection in the groin. Patients with active seroma drainage should be taken back to the OR for re-exploration of the groin with possible muscle flap creation, SPY limb angiography, and/or lymphatic ligation. Most often, hematoma complications can be managed nonoperatively if they are not associated with drainage, skin compromise, and/or expanding hematoma. The groin infection usually is the late sequelae of seroma and hematoma formation and requires surgical intervention. Pulmonary complications include transfusion-associated cardiogenic overload (TACO), transfusion-related acute lung injury (TRALI), acute respiratory distress syndrome (ARDS), and ventilator-associated pneumonia (VAP).4,19,20,21 TACO is improved with diuretics, while current techniques for TRALI treatment are supportive. The risk of VAP can be reduced through hospital-wide practices promoting patient and provider hygiene, along with specific maneuvers like raising the head of the bed to prevent aspiration.22,23 Patients with VAP and/or ARDS should be assessed daily for extubation with spontaneous breathing trials. If severe ARDS demonstrates no improvement with the various positive pressure techniques, venovenous extracorporeal membrane oxygenation should be discussed.24,25 Abdominal compartment syndrome is a serious complication detected in patients who are difficult to ventilate and have sustained intra-abdominal pressure greater than 20 mm Hg while paralyzed. This complication can be avoided with preemptive diuretics and assessment for hemorrhage and can be managed with decompression laparotomy, diuretics, dialysis/hemofiltration, and intravenous paralytic agents. Patients with ischemic colitis present with abdominal distension and/or pain, fevers, early bowel movements (post-op day 0/1), leukocytosis, and persistent acidosis. Early diagnosis with Flex Sig is crucial with this complication, which may require intraoperative revascularization of the IMA or diseased SMA for prevention. Treatment involves an exploratory laparotomy with possible bowel resection and supportive care.4 Acute kidney injury (AKI) is a renal complication avoidable by minimizing vasopressors, avoiding prolonged suprarenal aortic cross-clamping, and avoiding nephrotoxic drugs. AKI is diagnosed in patients with FENa greater than 1%, muddy brown casts in urine sediment, low urine output, and anasarca. Renal replacement therapies (ie, dialysis) may be necessary for treatment of AKI.4 Post-Discharge Late Complications to Monitor/Manage Despite the less invasive nature of EVAR lending to its lower mortality and lower index of length of stay, greater readmission numbers have been reported for EVAR than OSR after RAAA treatment.26 The highest median 90-day readmission costs are associated with endoleaks, a unique complication of EVAR that necessitates careful postoperative surveillance with contrast CT imaging and color duplex ultrasound .1,27 To avoid endoleaks that require urgent treatment (type I and III), EVAR stent grafts should be oversized since measurements of vessels from CT images in patients who are typically hypotensive and/or unstable are smaller than normal due to vasoconstriction and shock. Figure 2 Algorithm for postoperative ruptured aortic abdominal aneurysm surveillance based on Society of Vascular Surgery guidelines and Houston Methodist Hospital protocol.2 CT: computed tomography; EVAR: endovascular aortic repair; OR: operating room. Algorithm of postoperative ruptured AAA surveillance recommendations Other late complications include device migration and aortic graft infection. Device migration occurs if EVAR is done outside of the instructions for use, especially if there is an inappropriate proximal sealing zone causing the graft to drop into the aneurysm over time. Aortic graft infection affects both EVAR and OSR patients and may arise as a late complication. Patients may present with generalized sepsis, groin drainage, pseudoaneurysm formation, and ill-defined pain. Preventative measures include antibiotic prophylaxis, and treatment involves graft excision and OSR followed by antibiotic therapy. Patient Quality of Life As the healthcare model and research objectives shift towards improving patient outcomes, assessment of patient quality of life post-discharge is a fundamental step in a systems-based approach to creating center-specific policies that address recurrent issues reported by patients. To gauge the impact of the hospital visit and RAAA treatment on the patient's daily life, we recommend using the EQ-5D-5L survey, which analyzes five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.28 The survey can be distributed via email or through a patient portal. This quality-of-life surveillance can be used to improve patient outcomes through the help of social workers and case management in the outpatient setting. Conclusion Management of acute aortic conditions such as RAAA requires clear, timely communication between the various members on the medical team as the patient is transferred throughout the different phases of surgical care. We describe the current RAAA protocol at the HMH AATC to educate future vascular surgeons and serve as recommendations for low-volume aortic centers. Assessment of hemodynamic stability is critical from the moment of patient transfer to discharge, and permissive hypotension should guide fluid resuscitation. EVBC is recommended in patients who are hemodynamically unstable, followed by EVAR or OSR. The intraoperative and postoperative complications discussed should be prevented, if possible; however, early recognition and treatment in the OR or ICU may help lower the risks of morbidity, mortality, and long-term complications. Key Points HIPAA-compliant cloud-based image reviewing systems should be available in centers treating acute aortic syndromes to assess the patient disposition and determine whether the patient should go to the intensive care unit (ICU) or operating room (OR) upon arrival, as well as the type of operation required to treat the acute aortic syndrome. Patients with acute aortic syndrome who require surgical intervention should go directly to the hybrid OR, where all techniques are available to treat the condition. Ruptured abdominal aortic aneurysm (RAAA) Timeout must include the type and time of pressor, crystalloid, colloid, and blood product administration as well as the evaluation of patient consciousness level by the vascular surgeon. Permissive hypotension and the patient's level of consciousness should guide preoperative fluid resuscitation to avoid major blood loss and postoperative complications associated with volume overload and transfusion. We recommend endovascular balloon control (EVBC) in hemodynamically unstable patients regardless of the operative plan, be it endovascular repair (EVAR) or open surgical repair. The patient with RAAA should be treated with EVAR under local anesthesia with or without proximal EVBC, when possible. Surgeons should avoid EVAR for RAAA outside of instructions for use. Early recognition of postoperative complications in RAAA patients can guide early and appropriate management in the ICU or in the OR. Acknowledgements We would like to thank Dr. Alan Lumsden, Dr. Eric Peden, Dr. Charudatta Bavare, Dr. Linda Le, and Dr. Marvin Atkins for their help in shaping these guidelines. Competing Interests The authors have no competing interests to declare. 1 Abdulameer H, Al Taii H, Al-Kindi SG, Milner R. Epidemiology of fatal ruptured aortic aneurysms in the United States (1999-2016). J Vasc Surg. 2019 Feb;69 (2 ):378-384.e2. doi: 10.1016/j.jvs.2018.03.435 29960790 2 Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018 Jan;67 (1 ):2-77.e2. doi: 10.1016/j.jvs.2017.10.044 29268916 3 YouTube.com [Internet]. San Bruno, CA: YouTube; c2022. Atkins M, Rahimi M, Bavare C. Current management of ruptured AAA; 2021 Feb 1 [cited 2023 Jan 27]. Available from: 4 Starnes BW, Mehta M, Veith FJ. Ruptured Abdominal Aortic Aneurysm: The Definitive Manual. Switzerland: Springer International Publishing; 2017. 408 p. doi: 10.1007/978-3-319-23844-9 5 Raux M, Marzelle J, Kobeiter H, et al. Endovascular balloon occlusion is associated with reduced intraoperative mortality of unstable patients with ruptured abdominal aortic aneurysm but fails to improve other outcomes. J Vasc Surg. 2015 Feb;61 (2 ):304-8. doi: 10.1016/j.jvs.2014.07.098 25154564 6 Bath J, Leite JO, Rahimi M, et al. Contemporary outcomes for ruptured abdominal aortic aneurysms using endovascular balloon control for hypotension. J Vasc Surg. 2018 May;67 (5 ):1389-1396. doi: 10.1016/j.jvs.2017.09.031 29248238 7 YouTube.com [Internet]. San Bruno, CA: YouTube; c2022. Rahimi M, Berczeli M. Endovascular balloon control of aorta during RAAA with hypotension; 2021 Apr 1 [cited 2023 Jan 27]. Available from: 8 YouTube.com [Internet]. San Bruno, CA: YouTube; c2022. Rahimi M, Vowels T. Open repair of ruptured AAA with endovascular balloon control; 2021 Mar 1 [cited 2023 Jan 27]. Available from: 9 Knops E, van Schaik J, van der Bogt KEA, et al. Stent Graft Sizing for Endovascular Abdominal Aneurysm Repair Using Open Source Image Processing Software. Ann Vasc Surg. 2021 Feb;71 :411-418. doi: 10.1016/j.avsg.2020.08.126 32891744 10 UCTV.tv [Internet]. La Jolla, CA: University of California; c2023. 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PMC10000316 | Br Ir Orthopt J Br Ir Orthopt J 2516-3590 The British and Irish Orthoptic Journal 1743-9868 2516-3590 White Rose University Press 10.22599/bioj.289 VoR Original Article A Quality Assurance Audit of an Orthoptic-Led Virtual Neuro-Ophthalmology Clinic Smith Joe [email protected] 1 Hirst Nicola 2 Yagan Ali 3 1 Advanced Orthoptist, GB 2 Principal Orthoptist, GB 3 Consultant Ophthalmologist - Neuro-Ophthalmology and Adult Strabismus, GB CORRESPONDING AUTHOR: Joe Smith Manchester Royal Eye Hospital, GB [email protected] 10 3 2023 2023 19 1 714 26 9 2022 14 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Introduction: Neuro-ophthalmology is experiencing increasing demand. There is a lack of literature relating to how we deal with the capacity and demand issues, and the use of virtual clinics. Virtual clinics are well-recognised in other subspecialties to help deal with capacity and demand issues, with reports of non-medical-led clinics, and are supported by the National Health Services Long Term Plan and People Plan. We present a quality assurance audit of our orthoptic-led neuro-ophthalmology virtual clinic. Methods: The virtual clinic was developed in October 2014 to help deal with capacity and demand issues, however, only since 2019 have orthoptists been trained to virtually review. This paper provides a summary of a quality assurance audit that was completed to determine concurrence between orthoptic and consultant virtual reviews. Results: From January to August 2021, all patients attending the virtual clinic were reviewed by a trained orthoptist and then audited for concordance by a consultant neuro-ophthalmologist; 163 patients were identified. There was 100% agreement between orthoptic reviewers and consultants regarding visual function status and optical coherence tomography interpretation. Of the patients reviewed, 100% of patients were satisfied and 96% of patients would be happy to be seen in the virtual clinic again. Conclusions: Current demands on the neuro-ophthalmology speciality mean that we need to explore new ways of working. Our outcomes demonstrate a high level of agreement between orthoptists and ophthalmologists, and excellent patient satisfaction results. We hope this highlights where orthoptists can play an invaluable role in the care of neuro-ophthalmic patients and help deal with capacity and demand issues. neuro-ophthalmology virtual clinics orthoptic-led shared-care service models AHP-led pmcIntroduction Along with other ophthalmic subspecialties, neuro-ophthalmology is experiencing increasing demand in more recent times, which has been exacerbated by the COVID-19 pandemic. Before this, Ophthalmology was already recognised as the busiest outpatient speciality, with an expected further 30-40% increase in demand over the next 20 years (NHS Digital 2019; The Royal College of Ophthalmologist 2018). Virtual clinics are a well-recognised model of service delivery in other subspecialties such as medical retina (Lee et al. 2018; Kortuem et al. 2018; El-Khayat et al. 2018) and glaucoma (Gunn et al. 2018; Nikita et al. 2021; Koklanis and Thorburn 2021; Simons et al. 2021). There is also reported use of virtual clinics for the identification and referral of ocular melanocytic lesions (Karthikeyan et al. 2021). Virtual interactions have the potential to free up clinician time and appointment slots by reducing the time and space required for patient interactions and reducing did not attend rates (NHS England 2016). Virtual clinics and other forms of remote consultation within neuro-ophthalmology are not well documented in the literature before the COVID-19 pandemic. More recently reports of the use of telemedicine are emerging, however, many of these reports outline the options for use within the neuro-ophthalmology setting rather than comparing the validity of a remote model compared to a face-to-face model (Grossman et al. 2020; Ko and Busis 2020; Lai et al. 2020). Nevertheless, these reports are valuable in providing solutions for transforming the way that outpatient consultations are delivered, to address the imbalance between capacity and demand. A survey by Moss et al. (2020) reported an increase in the remote interpretation of tests in a neuro-ophthalmology setting from 27.6% pre-COVID to 32.2% during COVID. Delivering neuro-ophthalmology consultations remotely is difficult given the need for access to the physical examination and results from diagnostic testing to differentiate benign conditions from life-threatening neurologic emergencies (Grossman et al. 2020). This may be a reason why face-to-face interactions have taken precedence over virtual consultations in the past. Lai et al. (2020) suggested that the combination of various modalities may improve efficacy; initial phone triage and an in-person appointment for assessment followed by possible video consultation. The availability of ancillary testing will determine the ability to follow a patient remotely for optic nerve pathology, such as idiopathic intracranial hypertension, which in addition to history, requires a fundus view, a visual field, and optical coherence tomography (OCT) to determine clinical stability. The effective use of a virtual clinic model for patients referred with suspected optic nerve swelling has been reported by Jefferis et al. (2021). One hundred and thirty-three patients were virtually reviewed, retrospectively, by two consultant neuro-ophthalmologists who were blinded to the outcome of the face-to-face clinic. From the simulated virtual clinics, they found six out of one hundred and thirty-three had papilloedema and identified these as needing a face-to-face assessment. One hundred and twenty (90%) were discharged from face-to-face clinics and two ophthalmologists chose to discharge 114 and 99 respectively from the simulated virtual clinics. Only one patient would have been missed with serious pathology who had normal optic discs but reported diplopia at the face-to-face consultation (Jefferis et al 2021). Unrelated pathologies may be missed by solely reviewing the image without further information which supports the combination of using various virtual modalities as suggested by Lai et al. (2020), for example, including clinical questions as part of the virtual consultation to gather more information. Such reports support the development of neuro-ophthalmology virtual clinics and demonstrate their safety and effectiveness. The use of the non-medical workforce to help address challenges with capacity and demand is supported by the National Health Service (NHS) Long Term Plan and the NHS People Plan (NHS England 2019; NHS England 2020). To deal with the increasing demand for ophthalmic services, The Royal College of Ophthalmologists also recognised that new models of care must encompass maximum use of consultant time and expertise and enhance the multidisciplinary team with appropriate training and upskilling (The Royal College of Ophthalmologists 2017). Investing time and training in the non-medical workforce will help ease pressure on already stretched ophthalmic services. In the United Kingdom (UK), the Royal College of Ophthalmologists has worked with the British and Irish Orthoptic Society and other professional bodies to support the development of clinical competency frameworks to support the professional development of the multi-disciplinary eye health team. The Ophthalmic Common Clinical Competency Framework (Health Education England 2016) sets out standards for a systematic patient-centred approach to multi-disciplinary education and training, ensuring standardised and recognised competencies. The reports and plans discussed above highlight the need to change the way we deliver services and support the use of the non-medical workforce as a solution to capacity and demand issues. In this article, we present an audit of our orthoptic-led neuro-ophthalmology virtual clinic. We believe this to be the first report of a UK non-medical-led virtual clinic in neuro-ophthalmology. Methods Virtual clinic The Neuro-Ophthalmology and Orthoptic department at Manchester Royal Eye Hospital developed the virtual neuro-ophthalmology service in October 2014 to monitor and review patients with non-complex and stable neuro-ophthalmic conditions. The virtual clinic was established due to increasing demand for the neuro-ophthalmology service and aimed to streamline the patient assessment and reduce the number of patients waiting to be seen in a consultant-led clinic. Since the origin of the clinic, many service developments have been made based on regular clinical audits and increasing clinical demands. Clinical model At the time when this audit was being completed the virtual neuro-ophthalmology clinic ran twice weekly, with eight patients per session. Four of the patients attending were new patients with suspected optic nerve head swelling and were reviewed by a neuro-ophthalmology clinical fellow and the remaining 12 patients were follow-up patients who had varying diagnoses and were deemed as suitable for review by the orthoptic reviewers. Since this audit, the clinics have been remodelled and now run as four separate clinics, twice weekly, with four patients per clinic. The clinics are as follows 1) Idiopathic Intracranial Hypertension (IIH); 2) Tumour Monitoring; 3) Suspected Swollen Optic Nerves; and 4) General. The orthoptic reviewers review all patients attending the IIH and tumour monitoring clinic, and the neuro-ophthalmology fellows or consultants review all patients attending the suspected swollen optic nerves and general clinic. The general clinic includes patients with optic neuropathies and visual function abnormalities that do not fit the inclusion criteria for the other virtual clinics. Patients are migrated to the virtual clinics if deemed non-complex and not requiring face-to-face review by the medical team (e.g. consultant). Orthoptic reviewers In 2019, a business case was drafted, due to the increasing demand for the neuro-ophthalmic service, which proposed the development of new posts in which orthoptists would be upskilled to virtually review more stable patients who do not require face-to-face appointments. The business case included a full options appraisal (e.g. do nothing, do the minimum - such as develop waiting list initiatives, or develop these new posts) and risk assessment (e.g. quality, safety, and operational effectiveness). The business case was successful, with two orthoptists being appointed and trained to perform the virtual reviews. Both orthoptists had experience working with neuro-ophthalmic patients. One had previously completed an MSc module in neuro-ophthalmology (ORTH413: Specialist and Extended Roles in Neuro-Orthoptics and Neuro-Ophthalmology at the University of Liverpool) and the other was completing an MSc Advanced Clinical Practitioner course with optional neuro-ophthalmology modules (ORTH410 - Neurology for Advanced Clinical Practice and ORTH413 Neuro-ophthalmology for Advanced Clinical Practice at the University of Liverpool). Before independently reviewing the notes of patients that attended the virtual clinics, both orthoptists reviewed cases and attended feedback sessions in which they discussed the cases with a consultant ophthalmologist and received feedback. The supervising ophthalmologist would also use these sessions to teach the orthoptist about neuro-ophthalmic conditions, discussing presenting signs and symptoms, and the investigations required for diagnosis and management, with comprehensive discussions. These sessions were weekly and took place for over a year. Both orthoptists also worked in outpatient clinics and demonstrated competency in identifying visual function changes and posterior segment pathologies. Specific training for assessing optic disc pathologies using optical coherence tomography was undertaken with an external education provider. Finally, before deeming the orthoptic reviewers competent, a competency package was also completed that evidenced the ability to perform virtual reviews independently and ensure concerns were brought to attention before autonomy was achieved. A decision document (Table 1) was also produced to assist the orthoptic reviewers in making decisions and when cases needed to be brought to the attention of the ophthalmologist. Table 1 Neuro-ophthalmology virtual review decision document. CONDITION FINDINGS FOLLOW-UP Tumour monitoring Stable visual functions and OCT findings +- no new symptoms +- stable MRI 12 months Worsening of visual functions +- new symptoms Inform consultant or clinical fellow Arrange urgent F2F review Letter to relevant speciality +- arrange MRI Idiopathic intracranial hypertension Stable visual functions and OCT findings (no papilloedema to grade 1) +- no new symptoms +- tolerating medication 6 months Counsel regarding weight loss Counsel about pregnancy if on medications To consider stopping medications Worsening of visual functions +- new symptoms +- not tolerating medication Inform consultant or clinical fellow Arrange urgent F2F review or phone consultation Stroke and unexplained visual field defects Stable visual functions and OCT findings +- no new symptoms +- stable/normal MRI Discharge Worsening of visual functions +- new symptoms Inform consultant or clinical fellow Arrange urgent F2F review or phone consultation Optic neuropathies Improving/stable visual functions and OCT findings +- no new symptoms +- MRI confirmed ON or normal in AION +- Stopped steroid or under rheumatology if GCA Discharge Worsening of visual functions +- new symptoms Inform consultant or clinical fellow Arrange urgent F2F review or phone consultation Clinical assessment At the clinical assessment, depending on diagnosis, each patient has a bespoke pro forma completed. Three bespoke pro formas are used to take a clinical history and assess patients (Appendix A). These are 1) IIH; 2) compressive and general aetiologies; and 3) suspected swollen disc. Bespoke pro formas are used to ensure all relevant clinical information is obtained at the initial clinical assessment, including history and diagnostic assessments, as the initial diagnostic assessment is completed by a non-neuro specialist orthoptist or orthoptic assistant. The pro forma is filed into the patient's notes and given to the reviewer following the clinic. At each visit, all patients have visual acuity assessed using a logMAR acuity chart, colour vision assessed using the Ishihara, pupil reactions, visual fields (30-2 or Goldmann Perimetry in tumour monitoring patients and when previous static perimetry has been deemed unreliable), and optical coherence tomography of the optic disc and macula (TOPCON or Heidelberg). The images from the optic coherence tomography are viewed on a networked desktop. Figure 1 shows the clinic flow during the time of this audit. Figure 1 This flowchart details the patient flow through the virtual clinic during the time of the audit. All patients Attended for virtual assessment with the results then reviewed by an orthoptic reviewer with decisions made that were then checked for concurrence by a neuro-opthalmologist. This flowchart details the patient flow through the virtual clinic during the time of the audit Quality assurance During the time of this audit, all virtual reviews were checked by a consultant to ensure concurrence. Following the orthoptic reviewers being deemed competent, this is not necessary, however, assurance checks are continually undertaken to ensure no patients come to any clinical harm. Continuous monitoring is achieved by the consultants reviewing several complete virtual review sessions every four months to ensure full agreement with decisions made by the orthoptic reviewers. Reviews are also monitored on a random basis to ensure quality is consistently maintained. All virtual clinics are audited at two yearly cycles based on clinical governance requirements of the Trust. If issues are identified, the clinic is audited earlier and more regularly until assurance is fully assured. All patients attending the virtual clinics are also given a patient satisfaction survey to complete and data is collected and reviewed regularly to help make appropriate changes and improvements to the clinics, if deemed necessary. Results Audit of service From January to August 2021, all patients attending the neuro-ophthalmology virtual clinic were reviewed by a trained orthoptist and then reviewed for concordance by a consultant neuro-ophthalmologist; 163 patients were identified. Of these patients, 62 had a diagnosis of IIH, 88 with a compressive aetiology (included tumours, venous thrombosis, and aneurysms), three with optic neuropathies, two with swollen discs with unconfirmed diagnoses, two with crowded discs, one with a tilted disc, one with systemic lupus erythematosus, one with optic nerve head drusen, one with migraine, one with a field defect, and one that had an unremarkable ophthalmic assessment. Correlation between orthoptist and consultant There was 100% agreement between orthoptic reviewers and consultants regarding visual function status and optical coherence tomography interpretation. The level of agreement dropped to 95% (155/163) when it came to follow-up periods. The reason for the drop in agreement was mainly due to the orthoptic reviewer being overly cautious and reviewing patients sooner than deemed clinically necessary by the consultant. For example, the orthoptist would review a patient with a stable pituitary adenoma and visual functions in six months whereas the consultant deemed the patient would be safe to wait 12 months for clinical review. Unfortunately, as orthoptists cannot currently prescribe, there were occasions when the orthoptist was required to bring the patient to a face-to-face consultant clinic so a new medication could be prescribed whereas the consultant could prescribe the medication virtually and then arrange a normal review. This, however, does not cause clinical harm or visual compromise. Patient satisfaction The results of anonymised patient satisfaction questionnaires following virtual clinical assessment are presented, 145/163 (88.9%) completed the questionnaires. A summary of the responses is as follows: Do you feel the appointment was quicker than an appointment to see the ophthalmologist face-to-face? Yes 100% Were you given the opportunity to ask any questions at the assessment? Yes 100% Were you satisfied with the response? Yes 100% How would you rate your overall satisfaction with today's appointment? Very Satisfied 74% and Satisfied 26% Would you be happy to be seen in the virtual clinic again? Yes 96% Thirty-nine patients were randomly selected to contact following virtual review to ensure they were happy with their experience at the clinic and the quality of the letter they received from the orthoptic reviewers. Patients were contacted by phone call and 18 out of 39 patients were available to talk or responded to the voicemail left for them. Responses were as follows: Did you receive a letter explaining the findings from the virtual appointment? Yes 94% No 6% Was it clear from your letter which clinic your follow-up would be in, face-to-face or virtual clinic? Yes 89% No 11% Was it clear from the letter when your follow-up appointment would be? Yes 94% No 6% Did you feel satisfied with the amount of information provided in the letter? Yes 100% Would you be happy to be booked into the virtual clinic again? Yes 94% No 6% The negative responses related to the explanation of clinical findings referred to the use of medical terminology in letters that patients did not understand. To overcome this orthoptists have replaced such terms with more patient-friendly descriptions. For example, instead of referring to the OCT of the optic nerve, use of terms such as, the pictures or scans of the back of the eye. It was also clear that several letters did not have the specific clinic (e.g. face-to-face or virtual) and/or timeframe for the follow-up included. This has been improved by including clear instructions for follow-up at the top of letters. Finally, two patients reported that they would not be happy to be seen in the virtual clinic again, and this was because they had questions to ask on the day. This issue has been resolved by including a section for patient questions on the clinical pro formas with an option for the patient to be called with results. Discussion We believe this to be the first report of a UK orthoptic-led neuro-ophthalmology virtual clinic and we hope it highlights where orthoptists can play an invaluable role in the care of selected patients within the neuro-ophthalmology service. There is evidence of this within other ophthalmic subspecialties. El-Khayat et al. (2020) found in a virtual clinic setting, 100% agreement between three ophthalmic photographers and doctors in management decisions in patients with macular oedema secondary to diabetes or retinal vein occlusion during a 300-patient observation period. This resulted in a significant increase in the number of patients seen within clinics. A study by Koklanis and Thorburn (2021) evaluated the safety of an orthoptist-led glaucoma-monitoring clinic and found a substantial agreement of 85.71% between the orthoptists and ophthalmologists for the clinical management decisions of patients diagnosed with glaucoma. Furthermore, a study by Karthikeyan et al. (2021) found 98.6% concordance between optometrists and consultants for the diagnosis and management of patients with ocular melanocytic lesions. These numbers are very similar to the ones presented in our audit and support the safety and effectiveness of orthoptic-led virtual neuro-ophthalmology clinics. It is, however, important to have stringent quality assurance measures in place to ensure continuing safety and effectiveness. We discussed how we ensured this by consultants regularly reviewing patient records and performing quality assurance checks. Another important aspect of governance to consider, when developing new models of service delivery, is patient and service user input. We audited patient satisfaction and received excellent feedback from our patients with 100% of patients being very satisfied or satisfied with our model of service delivery, and 96% of patients being happy to be booked into the virtual clinic again. Karthikeyan et al. (2021) also reported that 100% of patients were satisfied and 95% would be happy to continue to be monitored by AHPs in their paper. This again supports the development of non-medical-led virtual clinics. As well as being a safe and effective model of service delivery, our clinic makes use of the non-medical workforce to help address challenges with capacity and demand. As mentioned earlier, this is in line with the NHS Long Term Plan and the NHS People Plan, as well as the Royal College of Ophthalmologists The Way Forward, which recommends working in new ways and utilising other health professionals for advancing the scope of practice (NHS England 2019; NHS England 2020; The Royal College of Ophthalmologist 2017). Our model of service delivery gives orthoptists more clinical responsibility which improves job satisfaction and enables continuous professional development. Operational effectiveness is also maintained as patients are reviewed in the same format and there is no decrease in clinical activity. In addition, this is an opportunity for cost-saving, as despite requirements for high banding of orthoptists (our orthoptists are Agenda for Change Band 7 and above), it costs less per session to fund an orthoptic reviewer. This model of service delivery does depend on the competence of orthoptists within the department, but we do present how competency was achieved with our orthoptists in the orthoptic reviewers section of this paper. Utilising the non-medical workforce means that ophthalmologists' time can be utilised more effectively, meaning that higher-risk patients can be reviewed face-to-face in a timelier manner. Finally, it is important to recognise that this paper is based on a quality assurance audit and only looks at a select number of patients over a short period of time. Future papers should include a greater number of patients over a longer period. Such papers will serve to support the development of further non-medical-led (virtual) clinics within the NHS and beyond, ensuring we can address the increasing challenge of capacity and demand. Conclusion In conclusion, the demands on the neuro-ophthalmology sub-speciality mean that we need to explore new ways of working. Non-medical led (virtual) clinics are well documented in other ophthalmic sub-specialities, and these models of service delivery are crucial to ensuring the safe and effective delivery of care to patients in a timely manner. Our outcomes demonstrate a high level of agreement between orthoptists and ophthalmologists, and excellent patient satisfaction outcomes. This shows that select neuro-ophthalmic patients can safely be monitored by orthoptists in a shared care model with a clear escalation protocol. We hope to have highlighted where orthoptics can play an invaluable role in the care of selected patients within the neuro-ophthalmology service. Future papers should include a greater number of patients over a longer period to demonstrate continuing effectiveness over time. Additional Files The additional files for this article can be found as follows: 10.22599/bioj.289.s1 Appendix A-1. IIH Proforma. 10.22599/bioj.289.s2 Appendix A-2. General and Tumour Monitorting Proforma. 10.22599/bioj.289.s3 Appendix A-3. Swollen Discs Clinic - Questionnaire. Competing Interests The authors have no competing interests to declare. 1 El-Khayat, AR, Anzidei, R and Konidaris, V. 2020. Ophthalmic photographer virtual clinics in medical retina. Int J Ophthalmol, 13 (4 ): 677-680. DOI: 10.18240/ijo.2020.04.23 32399423 2 Grossman, SN, et al. 2020. Neuro-ophthalmology in the Era of COVID-19: Future Implications of a Public Health Crisis. Ophthalmology, 127 (9 ): e72-e74. DOI: 10.1016/j.ophtha.2020.05.004 32387481 3 Gunn, PJG, et al. 2018. Acceptability and use of glaucoma virtual clinics in the UK: a national survey of clinical leads. BMJ open ophthalmology, 3 (1 ): e000127-e000127. DOI: 10.1136/bmjophth-2017-000127 4 Health Education England. 2016. The Ophthalmic Common Clinical Competency Framework - Curriculum. Available at: [Last Accessed: 23 September 2022]. 5 Jefferis, JM, et al. 2021. Is a virtual clinic model a safe and effective way for assessing patients referred with suspiciously blurred optic discs? The blurred disc clinic, European journal of ophthalmology, 31 (6 ): 3456-3462. DOI: 10.1177/1120672120976043 33246385 6 Karthikeyan, A, et al. 2021. Real-world outcomes of allied health professional-led clinic model for assessing and monitoring ocular melanocytic lesions'. Eye, 35 (2 ): 464-469. DOI: 10.1038/s41433-020-0873-5 32317788 7 Ko, MW and Busis, NA. 2020. Tele-Neuro-Ophthalmology: Vision for 20/20 and Beyond. Journal of neuro-ophthalmology, 40 (3 ): 378-384. DOI: 10.1097/WNO.0000000000001038 32604247 8 Koklanis, K and Thorburn, D. 2021. Orthoptist-Led Glaucoma Monitoring: A Pilot Quality Assurance Audit of the Reliability of Orthoptists in Glaucoma Management Decisions. Aust Orthopt J, 53 : 9-15. 9 Kortuem, K, et al. 2018. Implementation of medical retina virtual clinics in a tertiary eye care referral centre. British journal of ophthalmology, 102 (10 ): 1391-1395. DOI: 10.1136/bjophthalmol-2017-311494 29306863 10 Lai, KE, et al. 2020. Tele-Neuro-Ophthalmology During the Age of COVID-19. Journal of neuro-ophthalmology, 40 (3 ): 292-304. DOI: 10.1097/WNO.0000000000001024 32604249 11 Lee, JX, Manjunath, V and Talks, SJ. 2018. Expanding the role of medical retina virtual clinics using multimodal ultra-widefield and optical coherence tomography imaging. Clinical Ophthalmology, 12 : 2337-2345. DOI: 10.2147/OPTH.S181108 30532519 12 Moss, HE, Lai, KE and Ko, MW. 2020. Survey of Telehealth Adoption by Neuro-ophthalmologists During the COVID-19 Pandemic: Benefits, Barriers, and Utility. Journal of neuro-ophthalmology, 40 (3 ): 346-355. DOI: 10.1097/WNO.0000000000001051 32639269 13 NHS Digital. 2019. Hospital Outpatient Activity 2018-19. Available at: [Last Accessed 25 January 2023]. 14 NHS England. 2016. Demand Management Good Practice Guide. Available at: [Last Accessed 23 September 2022]. 15 NHS England. 2019. The NHS Long Term Plan. Available at: [Last Accessed 23 September 2022]. 16 NHS England. 2020. NHS People Plan. Available at: [Last Accessed 23 September 2022]. 17 Nikita, E, et al. 2021. Expansion of patient eligibility for virtual glaucoma clinics: a long-term strategy to increase the capacity of high-quality glaucoma care. British journal of ophthalmology, 107 (1 ): 43-48. DOI: 10.1136/bjophthalmol-2020-318556 34321213 18 Simons, AS, et al. 2021. Shared Care and Virtual Clinics for Glaucoma in a Hospital Setting. Journal of clinical medicine, 10 (20 ): 4785. DOI: 10.3390/jcm10204785 34682908 19 The Royal College of Ophthalmologists. 2017. The Way Forward Executive Summary. Available at: [Last Accessed 25 January 2022]. 20 The Royal College of Ophthalmologists. 2018. Workforce Census 2018. Available at: [Last Accessed 25 January 2022]. |
PMC10000317 | J Belg Soc Radiol J Belg Soc Radiol 2514-8281 Journal of the Belgian Society of Radiology 2514-8281 Ubiquity Press 10.5334/jbsr.3040 VoR Images in Clinical Radiology Pulmonary Artery Sling Blurs the Distal Trachea on Frontal Chest Radiography Jacquemin Quentin [email protected] 1 Nchimi Alain 1 1 Centre Hospitalier de Luxembourg, LU CORRESPONDING AUTHOR: Quentin Jacquemin Centre Hospitalier de Luxembourg, LU [email protected] 06 3 2023 2023 107 1 1821 12 2022 13 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Teaching Point: The pulmonary artery sling can be suspected on frontal chest radiography, not only by ancillary findings like lobe/lung emphysema or persisting atelectasis, but also blurring of the distal trachea or carina. Lung pediatrics bronchus trachea artery sling pmcCase History We report the case of a premature newborn, 30 weeks of gestation, without any noticeable birth event. On day one, he experienced respiratory stridor, polypnea, and intercostal retractions. Anteroposterior chest radiograph (CRX) showed right upper lobe atelectasis with air bronchogram. As his condition did not improve, an endotracheal tube was placed on day two. On control CRX , the tube was in an abnormally high position (asterisk), approximately 10mm under the vocal cords. The trachea was displaced to the right due to the right upper lobe atelectasis. Both the carina and the left main bronchus were not clearly depicted (arrow). Figure 1 Figure 1 Following axial computed tomography (CT) angiography , an aberrant origin of the left pulmonary artery (LPA) from the right pulmonary artery (RPA) was seen, with a subsequent posterior compression of the trachea on sagittal reformation , causing a tight stenosis of the pre-carinal trachea. The carina is located at the level of the seventh thoracic vertebral body. Coronal reformation shows an abnormal origin of the right upper lobe bronchus on the right, with abnormal narrowing of the tracheal segment below this origin, due to the abnormal origin and course of the LPA. Figure 2 Figure 2 Comments The term LPA 'sling' comes from the fact that it originates from the RPA and crosses the sagittal midline in between the trachea and esophagus to reach the left lung hilum. This causes a tracheal stenosis. A posterior mass effect on the lateral CRX is the most widely acknowledged finding related to this vascular anomaly. Nevertheless, lateral CRX is being progressively abandoned in neonates because of technical difficulties and radiation burden. Common but nonspecific findings for LPA sling on anteroposterior CRX include a lobar emphysema/atelectasis (most often the right upper lobe) persisting over time despite therapeutic measures. Herein we reported that undepictable trachea could be added in combination to these findings, to help raise the suspicion index for LPA sling for two reasons. First, the double superimposition of the pulmonary vasculature on the anteroposterior projection causes increased opacity and blurring of the right stripe of the distal trachea or the carina (depending on the level of the sling). Second, congenital bronchial malformations, potentially associated with pulmonary artery sling, such as displaced carina in this case, also contribute to a failure of depiction on anteroposterior CRX. Though valuable in terms of specificity for a mediastinal vascular ring, the identification of a blurred distal trachea (or carina) may lack sensitivity, given the common presence of nasogastric and/or endotracheal tubes and the displacement of the trachea over the lateral vertebral elements. According to the Wells and Landing's classification, there are two types of LPA sling depending on the position of the artery in relation to the carina. In Type 1, the carina is at its usual level (i.e., the fourth and fifth thoracic vertebral bodies), and the tracheobronchial anatomy is normal. In Type 2, the carina is located lower, at the level of the sixth and seventh thoracic vertebral bodies, the angle of the bronchial bifurcation is widened, and the bronchial anatomy can be altered, as in our patient, who had a type 2A malformation, as he additionally had a right tracheal bronchus . Competing Interests The authors have no competing interests to declare. 1 Newman B, Cho YA. Left pulmonary artery sling-anatomy and imaging. Semin Ultrasound CT MR. 2010; 31 (2 ): 158-70. DOI: 10.1053/j.sult.2010.01.004 20304323 |
PMC10000318 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1188 VoR Review Cardiovascular Nursing Workforce Challenges: Transforming the Model of Care for the Future Vozzella Gail M. DNP, RN, NEA-BC 1 Hehman Michelle C. PhD, RN [email protected] 2 1 Houston Methodist Hospital, Houston, Texas, US 2 Houston Methodist Academic Institute, Houston, Texas, US CORRESPONDING AUTHOR: Michelle C. Hehman, PhD, RN Houston Methodist Hospital, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 9099 18 11 2022 22 12 2022 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See The complexities of acute and critical care cardiovascular management demand specialty trained and experienced nurses to ensure quality patient outcomes. An ongoing nurse labor shortage threatens to destabilize the healthcare system and presents a twofold challenge: a decreasing supply of registered nurses and increasing demand for nursing services. This article describes the numerous forces driving the current nursing shortage as well as the impact of the coronavirus-19 pandemic on nurse job satisfaction and turnover. We present a reinvented model of nursing care as a framework for healthcare organizations to address nurse staffing challenges. cardiovascular nursing nurse workforce nurse shortage work environment model of care pmcIntroduction High-quality cardiovascular (CV) nursing requires a specialized mix of cardiac scientific knowledge, astute assessment skills in changing patient conditions, and the ability to react quickly with appropriate nursing interventions. In recent years, cardiac nursing has become progressively more complex, driven largely by advances in medical science such as supportive technology, medication, and device therapies as both a bridge to transplantation or destination therapy. These innovative tools, as well as expanded surgical and interventional techniques, have broadened competency requirements for CV nurses. Higher-acuity patients also increase nursing workload demands, a trend that will likely continue amid rising CV disease burden and a higher prevalence of comorbid conditions among hospitalized patients.1,2 A significant body of literature exists to demonstrate the impact of nursing workload, skill mix, and staffing on the quality of patient care.3,4,5,6,7 Having specialty trained and certified CV nurses has been shown to help decrease delays in cardiac referral and treatment, reduce hospital stays in patients with cardiac disease, and prevent rehospitalization.8,9,10 Against the backdrop of an ongoing nurse shortage, healthcare organizations need strategic plans to support, build, and retain a strong team of CV nurses. As the largest hospital workforce, nurses play a critical role in the stability of the healthcare system. The coronavirus-19 (COVID-19) pandemic underscored the gravity of acute nurse shortages, bringing renewed attention to the importance of a strong healthcare workforce. Since the early 1900s, the United States (US) has faced periodic nurse shortages as particular sociopolitical, economic, or technological forces rapidly escalate the demand for nursing labor.11,12 The current nurse shortage, however, also involves a decreasing supply of registered nurses (RNs) at the same time the demand for services continues to increase, leading to an ever-widening nurse labor deficit.13,14 Coordinating a lasting and effective response will require a nuanced understanding of the complex factors involved. This article reviews the numerous forces driving the shortage to identify areas of opportunity for CV nursing leadership to address staffing challenges. We also describe a new model of nursing care, providing a framework for healthcare organizations to improve the work environment by reducing workload burden and enhancing educational support for clinical staff. The Nurse Labor Shortage Nursing leaders and global health organizations have long warned about the growing nurse labor shortage as the world's population lives longer and requires more healthcare services.15 In the US, researchers estimate that due to the rising prevalence of chronic illness and an aging baby boomer generation, hospital utilization will increase 40% by the year 2025.16,17 Future growth of the nursing workforce, expected to increase 6% over the next decade, will not keep pace with the rising need for nursing services.18,19 For more than a decade, predictive workforce models have anticipated a nurse staffing crisis as demand continues to exceed supply; recent projections have become more worrisome as forecasts incorporate the additional impact of the COVID-19 pandemic on nurse retention.14 While nurse labor shortages impact all practice areas, the highly specialized nature of modern CV care requires adequate numbers of appropriately skilled and experienced nurses to ensure quality and safety. Even temporary staffing disruptions cause challenges for experienced CV nurses, who express frustration and worry when working with an inexperienced or constantly changing nursing team.20 Nurse staffing issues did not begin with the pandemic, but the events of the last 3 years have placed immeasurable strain on the entire healthcare system, exacerbating existing issues and exposing latent weaknesses. Due to the multifaceted nature of the nurse shortage, healthcare organizations are challenged to understand how all these factors influence staffing. Nursing Workforce Issues The US Bureau of Labor Statistics estimates the current RN workforce at 3,047,530 nurses.18 Cardiovascular nursing is the eighth largest inpatient specialty, with nearly 3% of nurses specializing in cardiac or CV care.21 Recent demographic surveys reveal shifts in race and ethnicity, educational attainment, and age distribution of nurses. While the profession is still predominantly white and female, younger nurses have increased the overall racial and ethnic diversity of the profession, making it more representative of the US population than ever before.18 This trend holds promising potential for reducing health disparities and improving equity and access to healthcare services because racial and language concordance between patients and providers improves communication, trust, and decision-making.22,23 The RN workforce also is becoming more educated and specialized, both of which correlate with improved care quality.4,24 Nearly half of all RNs report a bachelor's degree as their highest level of nursing education, and more than 1 million hold one or more nursing specialty credentials.18,25 Overall, the nursing profession is aging. In 2020, the median age of RNs rose to 52 years amid substantial shifts in age distribution across the profession .13 Nurses aged 65 years or older now comprise the largest single age cohort, with 19% of the workforce already at typical retirement age. More alarming, an even greater proportion of the total nurse workforce is nearing retirement, with 47% of nurses over the age of 50.13,26 Nearly half the workforce could retire in the next 10 to 15 years, a striking reduction both in sheer numbers and professional expertise. Collectively, older nurses possess an extensive amount of clinical proficiency, expert knowledge, and mentorship ability, and researchers anticipate an annual loss of more than 2 million years of nursing experience as these nurses retire.27 Figure 1 Age distribution of Registered Nurses (RNs) by year. The median age of RNs is 52 years and has remained consistent over the last decade. However, the overall age distribution of the nursing workforce has shifted significantly since 2013, with more than half of all RNs over the age of 50.13 Chart of RN age by year with distribution skewing significantly older since 2013 The implications of an aging nurse workforce extend beyond the clinical environment. Just as a significant percentage of clinical RNs near retirement, an even greater proportion of nurse faculty members are nearing retirement age, threatening to further upend an already strained nurse education system.28 Future growth of the profession depends upon a robust educational pipeline to ensure an adequate number of new nurses join the workforce each year. Despite substantial interest in the profession, nurse training programs lack sufficient capacity and are forced to turn away tens of thousands of qualified candidates each year. In 2021 alone, entry-level baccalaureate programs rejected 76,140 applications due to facility constraints, a lack of clinical placements, and/or a shortage of nursing faculty.29 With more than 63% of full-time nursing faculty members aged 50 or older, the nurse educator shortage will continue to worsen, further reducing educational capacity and restricting the growth potential of the profession.13 While the looming threat of an aging RN workforce has long been an issue of concern, the impact of COVID-19 on nurse turnover threatens to further destabilize the system. Nurse turnover is defined as any job move that results in either an internal shift between roles or an external move out of an organization or the profession entirely.30 High turnover rates negatively impact the quality of patient care, increase the financial and time resource burden of the healthcare system, and exacerbate nurse labor shortages.31,32,33,34 Disruptions in the healthcare delivery system throughout the COVID-19 pandemic predictably raised turnover rates as nurses adapted to changing work patterns, dealt with elder care and child care closures, and sought opportunities for travel nursing or remote telehealth positions.33 As a result of these challenges, the size of the nursing workforce initially plateaued, then dropped significantly when more than 100,000 RNs left the workforce in 2021, the largest single-year drop in 40 years.27 Measuring and anticipating nurse turnover is difficult because no standard operational definition currently exists. Instead, researchers evaluate individual intention to leave as the most accurate predictor of future nurse turnover, and recent data indicate that turnover intention has continued to rise. Between 22% and 44% of RNs intend to leave their current position within the next year, and 67% plan to leave within the next 3 years .31,32,33,35 Of the nurses who express intent to leave, only 38% plan to find a different position in clinical nursing, with most respondents planning to seek nonclinical opportunities or leave the profession entirely.33 This type of turnover, where nurses leave direct caregiving roles, significantly exacerbates the labor shortage, particularly when seen among early career nurses. This trend is likely to continue as nurses aged 35 and younger report the highest turnover intention as well as the lowest rates of job satisfaction and emotional well-being.35 Nurse emotional health, job satisfaction, and burnout are all correlated with key elements of the work environment.31,33 Figure 2 Intention to leave nursing and plans of those who intend to leave their position. A 2021 national survey of nurse work environments found that two-thirds of nurse respondents planned to leave their current position within the next 3 years.33 Of the respondents with plans to leave, only 38% intended to find a new position as a clinical nurse. Charts of RN intent to leave showing majority of RNs plan to leave current role and clinical nursing altogether Work Environment Issues Practicing in a workplace that is safe, empowering, and satisfying allows nurses to provide the highest quality care to patients and families while also fostering personal and professional development. A growing body of scientific literature demonstrates the influence of workplace health on quality indicators and patient outcomes.36,37 Healthier work environments are correlated with higher survival rates following cardiac arrest, lower 30-day inpatient mortality rates, lower rates of failure-to-rescue, and a reduction in factors associated with missed care.3,7,38,39 Nurses who practice in healthier workplaces report better overall psychological health, record greater job satisfaction, and demonstrate higher work engagement.37,40 A healthy work environment also is correlated with a lower incidence of workplace injury and lower nurse turnover intention.33,41,42,43,44 Recognizing these implications, the World Health Organization, National Academy of Medicine, and American Association of Critical Care Nurses have all emphasized the importance of promoting workplace health.34,45,46 The COVID-19 pandemic brought unprecedented challenges to the healthcare work environment. Frontline caregivers dealt with acute staffing shortages related to surging patient volume and acuity, continuously changing practice protocols, unavoidable exposure risks, crisis standards of care, inequities in disease risk and burden among already marginalized communities, and the collective trauma of millions of lives lost, many of whom were healthcare providers. Though the intensity of the crisis has waned, the emotional toll of delivering care during a global disaster, coupled with sustained staffing shortages, higher acuity patients, and increasing workload demands, leaves healthcare providers feeling unsupported in their work environment.34,47 Critical care nurses, particularly those who work in cardiac and CV intensive care units (ICUs), experienced high levels of burnout and increased turnover even before the pandemic began, attributed to the physical, emotional, and intellectual demands of their practice environment.48,49,50,51,52 COVID-19 intensified these workplace stressors, and CV nurses may have shouldered an even greater burden. Their specialized knowledge and expert clinical judgment proved invaluable during the pandemic given the high incidence of CV complications with COVID-19, but these skills also meant an increased likelihood of caring for the most complex and clinically demanding patients.20 As a result, ratings of the current nurse work environment are lower than ever before, driven largely by burnout, a lack of organizational resources, and unrealistic workload assignments.33,48,49,50,51,51 Individual nurse workloads are the combined result of staffing ratios, nursing skill mix, patient acuity, hospital throughput, technology management demands, and the availability of support personnel. High workload stress occurs when nurses are expected to complete too many tasks in the available amount of time. Nursing staff who feel unprepared for practice, either from a lack of experience or educational support, also can perceive higher workload burdens and experience greater work-related stress.53,54,55 Today's hospitalized CV patient requires more complex medical management and sophisticated nursing care even as hospital operations have begun to focus more on throughput and cost containment.56 Nursing responsibilities have expanded and patient acuity has increased--all while support personnel teams have been reduced and nurse staffing ratios have worsened. The resulting increase in workload burden is correlated with lower job satisfaction and higher intent to leave among direct care nurses.57,58 Nurse workforce characteristics and work environment issues are deeply interconnected, and no single force works in isolation to drive the current nurse shortage. For example, both individual and environmental factors shape nurse job satisfaction, which in turn influences turnover intention and eventual attrition from the job or the profession. In times of critical RN shortages, poor staffing leads to increased workload demands on the remaining RNs and contributes to low job satisfaction. Over time, poor job satisfaction fuels intent to leave and increases turnover, which worsens staffing on the unit and creates additional patient care workload burdens. These issues magnify and perpetuate one another, creating a continuous negative cycle between staffing, workload, job satisfaction, and turnover . To address the myriad challenges presented by the current nurse shortage, organizations must look toward comprehensive, systems-level strategies to improve retention by adding additional workplace support. Figure 3 Relationship between staffing, workload stress, job satisfaction, and turnover. Poor registered nurse (RN) staffing on clinical units leads to increased individual nursing workloads. Over time, this can reduce overall job satisfaction and increase an individual RN's intention to leave their current position. Intent to leave is strongly correlated with future nurse turnover and, as attrition rates climb, unit staffing worsens and perpetuates the whole cycle. Info-graphic showing circular relationship between RN staffing, workload, job satisfaction, intent to leave, and turnover Shaping a New Model of Nursing Care The current nurse shortage presents an opportunity to revolutionize traditional paradigms for nursing education and practice. Nursing leadership and healthcare organizations must focus on developing innovative plans with sustainable impact that address the immediate needs of nurse clinicians. The reinvented model of nursing care at Houston Methodist (HM) prioritizes the needs and experiences of clinical RNs while also acknowledging the reality of a worsening nurse shortage and the likelihood of continued staffing challenges. Given the magnitude and forecast of the current staffing crisis, primary and team-based models of nursing no longer offer a feasible template for providing safe and effective patient care. Rather than asking nurses to do more, the HM model of care integrates creative approaches to technology with enhanced education and training support to ensure high-quality, exceptional patient care regardless of nursing workforce transitions. The HM nursing model incorporates virtual ICU nursing, acute care telenursing, and an expanded nursing education team into the traditional nursing practice model, providing bedside clinicians with the tools and structural support necessary to work safely and efficiently at the highest level of their licensure. By reducing task-based workload, utilizing virtual nursing to supplement bedside clinicians, and expanding the number of unit-based nurse educators, the new care model maximizes the experience, skill mix, and size of the nursing workforce by improving efficiency without sacrificing care quality. Leveraging Digital Technology for Nursing Practice New models of nursing must streamline care delivery processes and enhance communication among patients and providers.15,34,35,59 By leveraging the pandemic-driven expansion of virtual nursing services into acute and intensive care settings, technology becomes a nurse extender, capable of improving patient safety while offloading tasks from bedside caregivers. This hybrid model of care integrates digital technology into the nursing workflow and provides real-time support to bedside clinicians from equivalently skilled and licensed RNs. At HM, a remote nursing operations center houses both a virtual intensive care unit (vICU) and a virtual acute care telenursing program that provide direct support to clinical RNs on dedicated patient care units across the hospital. In the vICU, experienced critical care nurses located in the remote operations center partner with bedside intensive care teams to provide enhanced observation of critically ill patients, enabling earlier identification of potential decompensation. Virtual coverage extends to four separate ICUs, including the cardiac ICU and CVICU. A total of 126 ICU beds are monitored by vICU nursing staff. High-resolution cameras and two-way audiovisual equipment allow for continuous, unobtrusive patient observation and remote consults at the bedside. The remote nursing team is composed of experienced cardiac critical care nurses who use their specialized knowledge, keen observation skills, and advanced critical thinking ability to integrate real-time physiological data with patient-specific risk factors. Combined with predictive analytic tools, the enhanced monitoring and observation allows the virtual nursing team to anticipate status changes and initiate early interventions. A separate virtual nursing unit was recently initiated to assist with admission and discharge procedures on acute care floors. The acute care telenursing staff provide virtual support to four separate inpatient units with a total of 137 beds across the hospital. Coverage includes units managing cardiac and CV patients, which frequently have complex medical histories, medication lists, and treatment modalities that make the admission and discharge process more time-consuming for nurses. Bedside RNs on these units also have higher nurse-to-patient ratios, increasing the potential for interruptions during these vital beginning and ending moments of an inpatient stay. When a clinical nurse requests support from the telenursing team, patients are connected to an experienced virtual nurse via video conferencing software on a bedside smart tablet. The one-on-one interaction allows for a more focused and comprehensive process whereby nurses have more time to answer questions, provide in-depth teaching, and address any issues with care coordination. Favorable patient responses and positive reception by both the bedside and virtual RN teams have pushed plans for expansion of telenursing to additional hospital units and to broaden services to further reduce task-based workload burden and offer timely support to clinical nurses. Additional telenursing responsibilities may include double-checking high-risk medications or treatments, monitoring and coaching clinical RNs through procedures, or serving as an on-call resource for new staff. This expanded hybrid model of nursing care aligns with recent evidence that indicates nurses are looking for technology integration that makes their work more efficient and flexible work options that maintain a connection to patient care.33,35,60 Defining and growing these new nursing roles meant that HM could offer an innovative work alternative to experienced RNs seeking a less physically demanding nursing position. These opportunities allowed the organization to remain competitive in a challenging RN job market while also improving retention of highly skilled CV nurses and protecting current staffing levels across the system. Redefining the Role of the Nurse Educator Another key component of the new HM model of care involves the expansion of the nursing education department to allow for the placement of a dedicated Professional Practice Leader (PPL) on each patient care unit. The PPL role extends the educational support given to nurses during new employee orientation and the nurse residency program, providing continuous mentorship, practice oversight, and just-in-time education to clinical RNs throughout their career. Nurses who function in the PPL role are highly educated expert nurse clinicians responsible for developing individualized, specialty-specific training and professional development plans for direct care nurses on their unit. PPLs oversee the transition to independent practice by new nurses, serve as a resource for organizational policies and standards of care, and implement practice changes according to the latest scientific evidence. They also ensure unit outcomes meet quality standards through practice audits, and their work has already improved the completion, accuracy, and timeliness of physical assessment documentation among nursing staff.61 Throughout the pandemic, the existing PPL team expertly navigated continuous policy and procedure changes, the rapid evolution of scientific knowledge, and social distancing challenges during onboarding. PPLs also were instrumental in the rapid development of an organization-wide nurse labor pool to respond to COVID-19 surges, further highlighting the value of a robust nurse education department and the need to increase the team to boost unit-based support. Enhancing PPL reach to every unit also may improve retention among novice and early career nurses by reducing transition-related stress.53 Transition stress, which results from a lack of mentorship and poor preparation for the complex demands of modern nursing practice, frequently leads to burnout and increased turnover.54 The complexities of modern CV nursing care increase the odds of transition stress. Nearly half of new nurses leave their position within the first year, primarily due to the large competency gap between educational preparation and professional practice; the added pandemic-related disruption of recent nurse graduate training experiences likely adds to stress and feelings of inadequacy.53,54,55 While a comprehensive nurse residency program like the one at HM has been shown to increase job satisfaction in novice nurses, the addition of a PPL on each unit provides a continuation of the residency's supportive educational structure and allows for more individualized training strategies in the event of knowledge gaps or process changes. PPLs in the CICU, CVICU, and acute care cardiac units ensure that direct care nurses develop confidence in their professional practice through appropriate experiential learning opportunities. Looking to the Future Future avenues for change to the HM model of care must be evidence-based and align with the strategic goal of reducing nurse workload burden while providing additional support for clinical staff. The relationship between nurses and technology is being restructured, and RNs are involved in every step of the technology integration process to ensure that new devices enhance nursing workflow. In addition to extending virtual nursing capabilities, pilot programs are being developed for smart devices that enhance physiologic monitoring, artificial intelligence-enabled predictive modalities, virtual reality skills training, and helper robots. Nurse researchers at HM also are initiating studies to evaluate the work environment across the organization to identify more specific areas of opportunity and tailor interventions according to nurse responses. Finally, nursing leaders are looking to enhance interprofessional communication and collaboration, which have been shown to independently improve nurse job satisfaction, reduce intention to leave, and improve patient outcomes.62,63,64,65 Conclusion The current nurse labor shortage presents healthcare organizations with unique challenges but also provides an ideal opportunity to revolutionize traditional models of care. At HM, innovative approaches to technology integration and educational support give nurses the resources they need to thrive in the current healthcare environment. The success of the HM model lies in its collaborative development process, solid technological infrastructure, and clearly defined responsibilities of the virtual care team and unit-based PPLs. Healthcare organizations will ultimately need to tailor approaches to their specific needs, but all strategic plans should include efforts that recognize the value of experienced nurses and invest in programs that support current staff and facilitate competency for novice nurses. Key Points The complex nature of modern cardiovascular management requires experienced, specialty trained nurses to ensure high-quality patient outcomes. The current nursing shortage presents a two-fold challenge as the supply of nurses continues to decrease at the same time demand for nursing services is on the rise. Major factors contributing to the nursing shortage include an aging RN workforce, higher rates of nurse turnover, and a more demanding healthcare work environment. A new model of nursing care at Houston Methodist incorporates virtual intensive care nursing, acute care telenursing, and an expanded nursing education team to provide bedside clinicians with the tools and structural support necessary to work safely and efficiently despite staffing challenges. Acknowledgements The authors would like to thank Nicole M. Fontenot, DNP, APRN, ACNP-BC, CCNS, CCRN-K, Alexis E. Hayes, PhD, MSN-Ed, APRN, FNP-BC, Joanne D. Muyco, DNP, RN, NE-BC, CNOR, and Carliss D. Ramos, DNP, RN, EBP-C, for their contributions in the planning and research for this manuscript. Competing Interests The authors have no competing interests to declare. 1 Gage A, Higgins A, Lee R. Cardiac critical care: The evolution of a novel subspecialty. Methodist DeBakey Cardiovas J. 2022 Apr-June;18 (3 ):24-29. doi: 10.14797/mdcvj.1092 2 Roth GA, Johnson CO, Abate KH, et al.; Global Burden of Cardiovascular Diseases Collaboration. 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Available from: 60 Keith AC, Warshawsky N, Talbert S. Factors that influence millennial generation nurses' intention to stay. J Nurs Admin. 2021 Apr;51 (4 ):220-226. doi: 10.1097/NNA.0000000000001001 61 Fontenot NM, Hamlin SK, Hooker SJ, Vazquez T, Chen HM. Physical assessment competencies for nurses: A quality improvement initiative. Nurs Forum. 2022 Jul;57 (4 ):710-716. doi: 10.1111/nuf.12725 35434794 62 Zangaro GA, Soeken KL. A meta-analysis of studies of nurses' job satisfaction. Res Nurs Health. 2007 Aug;30 (4 ):445-458. doi: 10.1002/nur.20202 17654483 63 Galletta M, Portoghese I, Carta MG, D'Aloja E, Campagna M. The Effect of Nurse-Physician Collaboration on Job Satisfaction, Team Commitment, and Turnover Intention in Nurses. Res Nurs Health. 2016 May 27;39 (5 ):375-85. doi: 10.1002/nur.21733 27233052 64 Lord H, Loveday C, Moxham L, Fernandez R. Effective communication is key to intensive care nurses' willingness to provide nursing care amidst the COVID-19 pandemic. 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PMC10000319 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1192 VoR Review Medical Management of Aortic Disease: If They Don't Need Surgery, What Do They Need? Saeed Mujtaba MD 1 Malahfji Maan MD [email protected] 1 1 Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, US CORRESPONDING AUTHOR: Maan Malahfji, MD Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 7077 24 11 2022 13 1 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Management of aortic disease has evolved significantly over the past few decades. A preemptive diagnostic approach with a multidisciplinary team and shared decision-making has led to improved clinical outcomes. Surgery is the cornerstone of management for most aortic conditions; however, medical therapy is now an important adjunctive therapy in most if not all patients. Herein, we review the role and evidence behind medical management of patients with aortic disease. aortitis aortic aneurysm aortic dissection pmcIntroduction Aortic diseases encompass a heterogenous spectrum of clinical presentations. Many pathologies are detected incidentally, while some develop insidiously and present acutely. Hyperacute and acute presentations can be deadly and include aortic dissections, rupture of an aneurysm, intramural hematomas, and penetrating aortic ulcers. The spectrum of aortic disease also includes connective tissue disorders and genetic syndromes as well as inflammatory aortic diseases. Management of aortic diseases historically has hinged on surgical intervention. However, medical management has evolved over the years and now plays an important role in the management of most aortic diseases. In patients who undergo surgery, medical therapy also has become key in postoperative care. Patient characteristics, comorbidities, underlying pathology, and the anatomical area of involvement are all factors that influence the need and type of recommended medical management. The American College of Cardiology/American Heart Association (ACC/AHA) recently released aortic disease guidelines that highlight the importance of medical therapy in most aortic conditions.1 In this article, we review the current evidence for medical therapies of various aortic diseases. Aortic Aneurysms Medical management of patients with thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) includes controlling cardiovascular risk factors, aggressive blood pressure control, patient education, lifestyle modification, genetic counseling, and serial imaging to optimize treatment, timing of surgery, and detection of other sites of aortic aneurysm development. A primary objective of medical management is to reduce the growth rate of aneurysms and the risk of complications. In patients with sporadic and degenerative aortic aneurysms, clinical trials of medical therapy are scarce because most studies have focused on genetic aortic conditions. In patients with TAA who have an average systolic blood pressure >= 130 mm Hg or diastolic blood pressure >= 80 mm Hg, use of antihypertensive agents is recommended to reduce the risk of cardiovascular events.1 Beta-blockers are recommended since they decrease heart rate, blood pressure, and the force of ejected blood on the aortic wall.2 In addition, angiotensin receptor blockers (ARBs) are reasonable adjuncts to beta blockers in achieving target blood pressure goals. ARBs are postulated to decrease aneurysm expansion by inhibiting intracellular mediators in the transforming growth factor-b signaling cascade and reducing matrix metalloproteinase (MMP) levels.3 MMPs have increased expression in aneurysms and promote proteolysis, hence propagating aneurysmal expansion and increasing the risk of dissection or rupture.4 However, there is no randomized data that shows a reduction in sporadic TAA size or growth rate with these medications. There is data on the protective effects of statins in TAAs, and the mechanism may be credited to anti-inflammatory properties and inhibition of MMPs.5 Statin use is also associated with a decrease in the incidence of dissection, rupture, surgical intervention, and death.5,6 In a retrospective study of patients who underwent thoracic endovascular repair for aneurysmal disease, patients who were treated with statins preoperatively had a significantly lower rate of perioperative complications and 5-year mortality.7 Cigarette smoking is a strong risk factor contributing to aneurysm formation, growth, and rupture. Cessation of smoking and avoidance of secondhand smoke should be encouraged in all patients. A retrospective study of three million patients demonstrated smoking to be a major risk factor for AAA, with a positive correlation to the quantity and duration of smoking and an inverse relation with years after smoking cessation.8 Blood pressure control helps reduce the risk of cardiovascular events such as myocardial infarction and stroke in patients with AAA.1 Antihypertensive therapies involving b-blockers are commonly employed for AAA, and observational data on statin use have been favorable as well.9,10 The current ACC/AHA aortic disease guidelines recommend the use of statins in patients with AAA.1 Studies show that statins are associated with a reduction in the risk of AAA rupture as well as mortality in patients with ruptured AAA.11 Antiplatelet therapy with low-dose aspirin is also recommended for patients with atherosclerotic TAA and AAA since atherosclerotic aortic diseases are considered a coronary artery disease equivalent.12 The use of doxycycline (a nonspecific MMP inhibitor) has shown efficacy in preventing TAA in a mouse model of Marfan syndrome, and its use is hypothesized to be beneficial for patients with Marfan syndrome; however, no human studies have been conducted.13 In contrast, fluroquinolones are associated with a potential increased risk of aortic dissection and rupture.14 A large population study associated fluroquinolone use with a very small increase in the rate of aortic aneurysm or dissection.15 Lifestyle modifications are an important aspect of aortic disease management. Exercise and activity limitation are particularly relevant in patients with aortic aneurysm. There are instances of aortic dissection and rupture in weightlifters with a moderate aortic aneurysm size (4 to 5 cm), suggesting that heavy weightlifting and bursts of strenuous exercise that lead to a rapid and detrimental increase in blood pressure should be avoided.16 In addition, there is an association between sudden emotional stress and TAA rupture, presumably due to sudden increases in blood pressure.17 Genetic Connective Tissue Diseases Genetic diseases that involve the aorta most often involve the thoracic portion, and these patients have a higher risk of dissection and rupture. Because aortic aneurysms arise earlier in these patients, it is important to identify those at risk of familial aortic aneurysmal disease (Table 1).1 Table 1 Risk factors for familial thoracic aortic aneurysm (TAA). TAA and syndromic features of Marfan Syndrome, Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome TAA at < 60 years of age Family history of TAA, intracranial or peripheral aneurysm History of unexplained sudden death at a young age in a second-degree relative Marfan syndrome is an autosomal dominant connective tissue disease caused by a mutation in the FBN1 gene that encodes fibrillin-1.18 As fibrillin-1 regulates the activation and signaling of cytokine transforming growth factor b (TGF-b), studies in a mouse model of Marfan syndrome showed that a deficiency of fibrillin-1 was associated with excessive signaling by TGF-b.19 Beta-blockers have been recommended in patients with Marfan syndrome to reduce the rate of aortic dilatation.20 Angiotensin receptor blockers also have shown efficacy in slowing the rate of aortic root dilation in patients with Marfan syndrome owing to TGF-b antagonism.3,19 A randomized controlled trial involving children and young adults with Marfan syndrome who received irbesartan or placebo demonstrated a decrease in the rate of aortic dilation.21 Another trial investigated the use of losartan in adult patients and also showed a reduction in aortic dilation rate.22 However, in a 2014 randomized controlled trial, no significant difference in the rate of aortic root dilation was found between b-blocker and ARB therapy.23 A meta-analysis showed that combination treatment with b-blockers and ARBs led to a lower rate of aortic dilation.24 Medical management of Loeys-Dietz syndrome is similar to patients with Marfan syndrome and relies on b-blocker use.1 Based on studies of mouse models, the use of ARBs is also considered,25 but there are no randomized trials in humans to show a reduction in aortic diameter growth or the risk of aortic events. Vascular Ehlers-Danlos syndrome (vEDS) is another inherited autosomal dominant connective tissue disease that involves the aorta, leading to progressive aneurysm formation or spontaneous dissection and/or rupture.26 Medical therapy is focused on managing and preventing vascular complications. Prophylactic measures include blood pressure control by b-blockers and atherosclerotic risk factor reduction.27 There have been trials on the use of celiprolol (a long-acting b-1 adrenoreceptor antagonist and partial b-2 agonist) to prevent dissections and ruptures, with one study showing a three-fold decrease in fatal vEDS-related events and another study demonstrating that a daily dose of celiprolol (400 mg) provided optimal protection.28,28,29,30 Aortic Dissection Emergent surgery is the standard of care in patients with ascending aortic dissections.1,31,32 Initial medical management involves anti-impulse therapy and pain management. Beta-blockers decrease stress on the aortic wall by reducing heart rate and blood pressure, hence slowing the progression of dissection and maintaining end-organ perfusion.33,34 It is preferred to reach a target heart rate < 70 bpm and systolic blood pressure between 100 mm Hg and 120 mm Hg for adequate organ perfusion.35 Beta-blockers have a class I recommendation to lower blood pressure in patients with aortic dissection (AD). In addition, intravenous nitroprusside, nicardipine, and nitroglycerin can be used as adjuncts.33,34 Suzuki et al. examined data of 1,301 patients from the International Registry of Acute Aortic Dissection and showed that type A and type B AD patients who were discharged on b-blockers had better outcomes, while calcium channel blockers were associated with longer survival in type B AD.36 In patients with contraindications to b-blockers, esmolol or nondihydropyridine calcium channel blockers can be used, while labetalol also offers an advantage of alpha and beta antagonism.34 In addition to lowering blood pressure, it is important to provide adequate pain relief to patients. Uncontrolled pain can activate the sympathetic response, resulting in a high blood pressure, heart rate, and propagation of the tear.34 Patients with AD also require long-term medical management. Oral antihypertensive regimens that include b-blockers, ARBs, and angiotensin-converting enzyme inhibitors improve long-term outcomes in patients.37 Figure 1 provides an overview of the main targets of medical therapy in patients with aortic disease. Figure 1 Summary figure of aortic disease management. BP: blood pressure; SBP: systolic blood pressure; DBP: diastolic blood pressure; ARBs: angiotensin receptor blockers; ASCVD: atherosclerotic cardiovascular disease Summary figure of aortic disease management Inflammatory Aortic Diseases Aortitis is defined as a nonatherosclerotic and noninfectious inflammatory process that involves the tunica media with or without involving the adventitia.38 Evidence is scarce on the incidence of inflammatory aortic diseases, or aortitis, primarily due to their multifactorial nature and lack of a definitive classification.38,39 However, we have epidemiological data on the most common causes such as giant cell arteritis (GCA) and Takayasu arteritis (TA).39 According to a study of 255 patients who underwent surgery for thoracic ascending aortic aneurysm, the most common histopathological pattern in patients with aortitis (n = 35) was granulomatous giant cell (n = 20).40 The study also associated aortitis with advanced age, female gender, and a higher prevalence of cardiovascular risk factors.40 Another study that analyzed resected thoracic aorta specimens of 788 patients with aortitis found that GCA was the most common histopathological finding (76.9%) and more frequent in women. However, out of 38 patients with noninfective aortitis, 92.3% had isolated aortitis with no established systemic disease.41 Aortitis commonly involves the thoracic aorta, resulting in aneurysmal dilation of the aortic root and/or ascending aorta owing to an inflamed and thin aortic wall.42 Although AD and rupture can occur, massive fibrosis can be a protective factor as seen in the healing phase.31,40,42 Another rare cause of aortitis is IgG4-related disease, which can cause lymphoplasmacytic thoracic aortitis and chronic periaortitis involving the abdominal aorta; the latter can be associated with retroperitoneal fibrosis.43 Surgical repair of an inflamed aortic aneurysm may not have favorable results due to the fragility of aortic tissue.41 Hence, immunosuppressive agents are the primary treatment of choice. High-dose oral glucocorticoids (prednisone at 40 - 60 mg/dL) and/or intravenous pulse steroid therapy are started as early induction therapy.44 Disease-modifying antirheumatic drugs (DMARD) are used as adjuncts in select patients who are at risk of relapse, develop glucocorticoid-related adverse effects, or require prolonged glucocorticoid therapy.45,46,47 Methotrexate and tocilizumab are frequently used DMARDs in combination with steroids for the management of GCA and TA.48,49 Nonbiological DMARDs (eg, methotrexate, hydroxychloroquine, azathioprine, sulfamethoxazole, and leflunomide) are first-line agents, and biological DMARDs (eg, tocilizumab or tumor necrosis factor inhibitors) are considered second-line agents in TA.44 Initial medical therapy for active TA and GCA reduces the active inflammatory state. Elective surgical repair of TAA for patients with TA and GCA should be delayed until the acute inflammatory state is treated and quiescent . Figure 2 A case highlighting the importance of medical management in a patient with aortic disease. A 47-year-old man with a history of ascending aortic grafting and aortic valve replacement who underwent follow-up magnetic resonance angiography. The study showed a large aneurysmal formation (yellow arrow) just proximal to the ascending aortic graft (green arrow). Another small aneurysm (blue arrow) was seen at the aortic isthmus along with significant aortic wall thickening and enhancement on contrast angiography, consistent with aortitis (red arrows). Review of the histopathology slides from the aortic wall demonstrated wall thickening and extensive fibrosis along with a dense inflammatory infiltrate, with features suggestive of IgG4-related disease. The patient was started on immunomodulators and his follow-up imaging showed stable aortic dimensions. A case example of aortitis Future Directions There are many gaps in the current literature on medical management of aortic diseases, although a significant number of trials are being conducted that may provide clarity on the optimal approach. Active randomized controlled trials are evaluating the benefits of physical conditioning in patients with aortic diseases, especially postoperative patients.50 The incorporation of nonpharmacological/lifestyle modifications in tandem with a focus on improving patient-reported health-related quality of life is of paramount importance and may improve outcomes.51 Since data does not provide distinct risk stratification on gender differences and race-based differences in mortality and morbidity, it will be important for future studies to focus on these aspects to improve outcomes across a spectrum of demographics. The mechanical properties of normal and diseased aortic tissue are also of great research interest. Studies using 4-dimensional magnetic resonance imaging to evaluate the wall shear stress and other aspects of aortic flow may provide important data crucial for a tailored management of these patients.52 All of the above are pertinent areas that need further research. Conclusion Although surgery is the definitive treatment for the majority of aortic diseases, medical management has evolved significantly to supplement surgery. Control of blood pressure, cholesterol, lifestyle factors, and comorbidities are all important and meaningful targets to optimize outcomes in aortic disease patients. Further research is needed to develop effective medical therapies to prevent and treat both sporadic and genetic aortic aneurysms. Key Points While surgery remains the mainstay of management of many aortic diseases, optimal medical therapy and control of risk factors can improve patient outcomes. Early screening of at-risk patients and initiation of medical therapy can reduce complications in patients with aortic disease. Further research is needed to develop and test medical therapy for various aortic diseases. CME Credit Opportunity Houston Methodist is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Houston Methodist designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Click to earn CME credit: learn.houstonmethodist.org/MDCVJ-19.2. Competing Interests Dr. Malahfji receives support from the Houston Methodist Research Institute and from Guerbet, LLC. 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PMC10000320 | J Cogn J Cogn 2514-4820 Journal of Cognition 2514-4820 Ubiquity Press 10.5334/joc.266 VoR Research Article Inhibitory Learning with Bidirectional Outcomes: Prevention Learning or Causal Learning in the Opposite Direction? Chow Julie Y. L. [email protected] 1 Lee Jessica C. 2 Lovibond Peter F. 1 1 UNSW, Sydney, Australia 2 The University of Sydney, Australia CORRESPONDING AUTHOR: Julie Y. L. Chow School of Psychology, University of New South Wales, Sydney NSW 2052, Australia [email protected] 10 3 2023 2023 6 1 1914 11 2022 24 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Influential models of causal learning assume that learning about generative and preventive relationships are symmetrical to each other. That is, a preventive cue directly prevents an outcome from occurring (i.e., "direct" prevention) in the same way a generative cue directly causes an outcome to occur. However, previous studies from our lab have shown that many participants do not infer a direct prevention causal structure after feature-negative discrimination (A+/AB-) with a unidirectional outcome (Lee & Lovibond, 2021). Melchers et al. (2006) suggested that the use of a bidirectional outcome that can either increase or decrease from baseline, encourages direct prevention learning. Here we test an alternative possibility that a bidirectional outcome encourages encoding of a generative relationship in the opposite direction, where B directly causes a decrease in the outcome. Thus, previous evidence of direct prevention learning using bidirectional outcomes may instead be explained by some participants inferring an "Opposite Causal" structure. In two experiments, participants did indeed report an opposite causal structure. In Experiment 1, these participants showed the lowest outcome predictions when B was combined with a novel cause in a summation test, and lowest outcome predictions when B was presented alone. In Experiment 2, B successfully blocked learning to a novel cue that was directly paired with a reduction in the outcome, and this effect was strongest among participants who endorsed an Opposite Causal structure. We conclude that previous evidence of direct prevention learning using bidirectional outcomes may be a product of excitatory rather than inhibitory learning. causal learning prevention causal structure feature negative bidirectional outcomes Australian Research Council 10.13039/501100000923 DP190103738 DE210100292 This study was funded by an Australian Research Council Discovery Project Grant [DP190103738] to Peter Lovibond. Jessica Lee was supported by a Discovery Early Career Researcher Award from the Australian Research Council [DE210100292]. pmcIntroduction The ability to learn about causal or predictive relationships between events in the environment is important for adaptation. It allows the person or animal to anticipate significant outcomes like the presence of threat or rewards. In a generative causal relationship, the presence of the candidate cause (sometimes referred to as a cue) directly predicts the presence of the target outcome. For example, the presence of rain clouds signals incoming rain. Also important, however, is the ability for people to predict the absence of significant outcomes. Preventive relationships involve the absence of the outcome when the cue is present. Although there are many ways in which people might acquire causal beliefs, for example through verbal instruction, we are specifically interested in how people learn from covariation between events in the environment -- that is, evidence collected from their own experience with the cue and the outcome. Learning from covariation has a longstanding history in associative learning and cognitive psychology. The basic assumption here is that causation can be inferred from statistical patterns such as the co-occurrence or non-occurrence of events (e.g., Cheng, 1997; Shanks, 2004). When human participants are exposed to contingencies where the probability of the outcome occurring increases or decreases in the presence of the cue, they reliably rate the cue as generating or preventing the outcome respectively (Shanks & Dickinson, 1988). Accordingly, most theories of associative learning or causal inference assume that learning about a preventive relationship is largely the same as learning about a generative causal relationship, that is, causation and prevention are equivalent but opposite in sign (e.g., Rescorla-Wagner (RW) model, Rescorla & Wagner, 1972; Power PC Theory, Cheng, 1997, Novick & Cheng, 2004; Causal Support, Griffiths & Tenenbaum, 2005). However, the idea that causation and prevention are equivalent but opposite in sign disguises an important asymmetry in the conditions required to both learn and express these two types of relationship. Generative causal learning can be achieved by pairing a cue with an outcome, but preventive learning cannot be achieved by simply pairing a cue with the absence of an outcome. This is because the latter situation is indeterminate - the cue could be associated with the absence of an indefinite number of different outcomes. Instead, preventive learning requires some expectation that a particular outcome should occur, either through another causal agent or the context (i.e. base rate). In the laboratory, prevention learning is often studied using a feature negative (FN) design, in which a causal cue A is followed by the outcome except on trials where a preventive feature B is also present (A+/). Although associative and cognitive models differ in the assumed psychological processes underlying learning, implicit in both associative and cognitive models of learning is that the conditions or experimental procedure for acquiring preventive relationships are not symmetrical to causal relationships. For example, in the Rescorla-Wagner model, inhibitory learning is driven by expectation of an outcome that does not occur (negative prediction error). The asymmetry is also reflected in the use of different equations for generative and preventive learning in Cheng's (1997) Power PC theory. Cheng addresses this asymmetry explicitly and asserts that "treating a preventive cause as the mirror image of a generative cause...is problematic" (1997, p.388). To cite an example provided by Cheng, if a researcher is interested in the efficacy of a treatment in causing headaches, they need only administer the treatment to a population to determine whether it is effective or not. In contrast, the efficacy of a treatment in preventing headaches cannot be determined by presenting the treatment if the patient taking the treatment does not already have a headache (i.e., causal agent is missing). Under these conditions, the preventive power of the cue cannot be determined. Similarly, generative causal learning can be expressed behaviourally (for example in anticipatory responding) simply by presenting the cue, but preventive learning is typically behaviourally silent (Zimmer-Hart & Rescorla, 1974; Konorski, 1948), and additionally requires the presence of a causal cue in order to be detected - in the associative literature this is known as a summation test (Pavlov, 1927). Despite this asymmetry in how we learn about generative vs preventive relationships, both cognitive and associative models appear to assume that once learnt, the representations underlying generative and preventive learning are essentially the same, and differ only in the direction of their action on the outcome. Cognitive models like Power PC (Cheng, 1997), and Bayesian models that propose similar causal power principles (e.g., Griffiths & Tenenbaum, 2005), typically imply that generative and preventive causes are both encoded by the learner as acting directly on the outcome. In line with this interpretation, when both generative and preventive links are included in the same causal diagram, they are both depicted by a direct link between a cue and an outcome but with a positive or negative weight to indicate causation or prevention (e.g., Carroll et al., 2013; Gong & Bramley, 2021). Certain models are even more explicit in their assumption that preventive and generative learning differ only in the direction of their action. In this paper, we will focus on the Rescorla-Wagner model (Rescorla & Wagner, 1972). The RW model has been widely influential in human and animal associative learning and makes clear, testable predictions. This model assumes that a person or non-human animal tracks the covariation between events through mental links connecting representations of these events in memory. The strength of the mental links between cue and outcome change flexibly according to experience. A cue that reliably predicts the presence of an outcome (i.e., an excitor) comes to directly activate the representation of that outcome, acquiring positive associative strength. In contrast, a cue that predicts the omission of an outcome (an inhibitor) is said to directly suppress the outcome representation, acquiring negative associative strength (Konorski, 1948; Rescorla, 1969). The RW model is clear in presenting these two types of learning as opposite to each other. Excitation and inhibition are seen as lying on a single dimension of associative strength, with excitors having positive associative strength and inhibitors having negative associative strength. Researchers have previously noted the similarities between factors that influence Pavlovian conditioning in animals and human contingency learning (e.g., Alloy & Abramson, 1979; Shanks & Dickinson, 1988), suggesting that these associative processes, i.e., ability for a cue to activate or suppress mental representation of an outcome, may govern the extent to which we judge a putative cause and effect to be causally related (Hume, 1888; Dickinson, 1980). Thus, although originally developed to account for animal conditioning data, associative learning models like the RW model have been suggested to provide a good account of causal learning in humans (Dickinson, Shanks & Evenden, 1984). We have previously argued that the RW model maps onto the idea of prevention learning in so far as excitors and inhibitors act directly on the same outcome representation; that is, causation and prevention are symmetric opposites of each other both in terms of the continuum of associative strength and the structure underlying learning (Lee & Lovibond, 2021). Our interpretation of the RW model is consistent with other contemporary associative accounts of inhibition, including those made by Rescorla and Wagner separately (e.g., Rescorla, 1969; Brandon, Vogel & Wagner, 2003). We refer to this causal structure as "direct prevention". Note that we will refrain from using the term "conditioned inhibition" since this term is often used to describe a learning phenomenon (i.e., a negative feature passing a summation test) that is consistent with multiple underlying causal structures (Lee & Lovibond, 2021; see Sosa, 2022 for a review). However, an alternative causal structure for inhibitory learning has also been identified in the associative literature by Rescorla (1985) and Holland & Lamarre (1984). These researchers showed that in an A+/ discrimination, a learner may encode B not as directly inhibiting the outcome but as modulating or gating the relationship between A and the outcome. That is, A alone causes the outcome to occur, but when B is also present, A no longer causes the outcome to occur. This is known as negative occasion setting in associative learning (Bonardi, Robinson & Jennings, 2017; Fraser & Holland, 2019). We will refer to this causal structure as "modulatory", since it explicitly describes the action of a preventive cue as modulating the action of a causal cue rather than acting directly on the outcome. Evidence for modulatory learning comes from studies showing that the ability of the feature to modulate another cue's relationship with the outcome is largely independent of its own relationship with the outcome (Fraser & Holland, 2019). Thus, modulatory learning provides a formal alternative causal structure to direct prevention learning that not only specifies the need for a generative cause to be present during learning, but also assumes this cause is explicitly incorporated into the learned causal structure. To our knowledge, direct prevention and modulation are the two most clearly specified causal structures that represent a negative relationship between a cue and an outcome. When cues are presented in an A+/ arrangement, the causal scenario is ambiguous and it is unclear which causal structure is "correct". In the animal conditioning literature, a key determinant of what is learned is whether the AB compound is presented serially or simultaneously. Animals typically show modulatory learning (negative occasion setting) to the feature when the compound stimuli are presented serially (A is followed by the outcome unless preceded by cue B, i.e., A+/B -> A-), and something like direct prevention learning (conditioned inhibition) when the stimuli are presented simultaneously (A+/AB-; e.g., Holland & Gory, 1986). However, there is relatively little evidence for direct prevention learning in humans. In our work on self-reported causal structures after FN training, we have observed substantial individual differences in the content of inhibitory learning (Lee & Lovibond, 2021). We have previously shown that in addition to a direct prevention causal structure, many participants report learning a modulatory causal structure regardless of whether a serial or simultaneous design is used (Lee & Lovibond, 2021; Lovibond & Lee, 2021). A third group of participants reported learning only about which outcome will occur with each combination of stimuli; we classify this group of participants as Configural learners, in the sense that they learn about all cues presented together (e.g., in a compound) rather than trying to infer their individual roles . Importantly, suppression of outcome predictions in a summation test, where B is presented with a different causal cue, is usually incomplete in human causal learning (Karazinov & Boakes, 2007; Lee & Livesey, 2012), and much smaller in magnitude compared to non-human animals. According to the RW model, if B has acquired negative associative strength after FN discrimination, one would expect the summation of opposing associative strengths (positive associative strength of the causal cue and negative associative strength of B) to produce much stronger suppression of outcome predictions than is typically observed. Further evidence against the idea of arithmetic summation of opposing causal strengths comes from recent work demonstrating that summation is heavily influenced by the similarity between trained and transfer stimuli, suggesting that the summation test is better characterised as a test of generalisation (Chow et al., 2022). Finally, in both humans and animals, repeated presentations of a preventive cue alone do not lead to a loss of its preventive properties, in contradiction to the predictions of the RW model (Lovibond, Chow, Tobler & Lee, 2022; Zimmer-Hart & Rescorla, 1974). Thus, evidence of direct prevention learning is limited, especially in human causal learning (and maybe also in animals). Figure 1 Diagrammatic Representation of All Four Causal Structures. Note: Pointed arrowheads represent an excitatory connection, and flat arrowheads represent an inhibitory connection. Diagrammatic Representation of All Four Causal Structures Melchers, Wolff and Lachnit (2006) proposed that the difficulty in demonstrating direct prevention learning of the type proposed in the RW model in humans could be a product of the type of outcome used in causal learning studies. These researchers pointed out that most studies employ outcomes that can only vary unidirectionally (e.g. an allergic reaction that either occurs or does not occur, but there is no anti-allergic reaction). They suggested that unidimensional outcomes do not accurately reflect the symmetrical continuum of associative strengths described in the RW model. Instead, they proposed employing bidirectional outcomes in causal learning tasks, where the outcome could increase or decrease relative to some baseline. According to Melchers et al. (2006), this procedure would allow the feature B to elicit an expectation that the outcome would decrease below baseline, an outcome they described as being in line with the assumptions of the RW model (i.e., negative associative strength). Thus, they argued that if a bidirectional outcome were employed during a FN discrimination, participants would be more likely to infer that B directly prevents the outcome from occurring. They provided some evidence for this claim by showing that the inhibitory properties of the feature B could be extinguished by presenting the feature alone (B-) when the outcome was bidirectional but not when it was unidirectional. The idea here is that when a bidirectional outcome is used, negative associative links could increase from a negative value to zero, allowing the feature to lose its inhibitory power. However, there is an alternative way in which people could interpret the role of the feature when FN training (A+/AB-) is carried out with a bidirectional outcome. If we consider the outcome below baseline as a distinct outcome in itself, it is plausible that instead of acquiring prevention learning, where the feature B prevents the outcome signalled by A, participants might instead infer that B directly causes the opposite outcome to that elicited by A. For example, if cue A predicted an increase in outcome level and AB predicted no change, participants might infer that B directly caused a decrease in the outcome. This "opposite causal" structure is distinct from both of the inhibitory structures, prevention and modulation, described earlier. Opposite causal learning is different from direct prevention learning since it involves a generative causal link between the cue and the opposite outcome (in associative terms, the feature activates a representation of the opposite outcome, rather than suppressing a representation of the actual outcome presented). An opposite causal structure is also distinct from a modulatory causal structure since it involves a direct link between the feature and the outcome, and therefore the feature is able to be active on its own without an existing source of excitation (e.g., another causal agent present) for its effect to be seen. In summary, the opposite causal structure is distinct from genuine inhibitory structures like direct prevention and modulation, as it involves a direct excitatory connection between the feature and an (opposite) outcome. In contrast, both direct prevention and modulation involve the inhibition or suppression of an outcome, either directly (direct prevention) or by gating the relationship between a causal cue and an outcome (modulation). Diagrammatic representations of all four causal structures potentially inferred in a FN discrimination task (direct prevention, modulation, configural and opposite causal) are shown in Figure 1. The goal of the present study was to test this alternative explanation that when presented with bidirectional outcomes in a FN discrimination, some participants acquire opposite excitatory learning to the feature. Across two experiments, we tested this hypothesis by incorporating the new opposite causal structure into our previous method for assessing individual differences in causal structure inference (see Experiment 1 Procedure). We used a modified allergist task with the same causal scenario used by Melchers et al. (2006) and Lotz and Lachnit (2009), with hormone levels as outcomes that either increased, decreased or were unchanged. Our primary hypothesis was that a FN discrimination with a bidirectional outcome could be solved by assuming that the feature directly causes a reduction in hormone level (opposite causal) rather than preventing the hormone level from increasing. Thus, we expected a proportion of participants to not only report such an opposite causal structure to the feature alone (i.e., that it causes a decrease in hormone level), but also that these individuals would show the greatest transfer effect in a summation test compared to participants who reported an inhibitory (direct prevention or modulation) causal structure, where as noted earlier transfer is often incomplete. These findings would suggest that we have identified a novel causal structure when a bidirectional outcome is used, and demonstrate that opposite causal is distinct from other known inhibitory structures. Experiment 1 The aim of Experiment 1 was to explore whether participants endorse an "opposite causal" structure to explain the role of the feature B in an A+/ negative discrimination when the outcome is bidirectional in nature. In our design and the design of Melchers et al (2006) and Lotz & Lachnit (2009), the term "bidirectional" is used to refer to outcomes that can increase or decrease from baseline, while "unidirectional" refers to (binary) outcomes that can only increase from baseline (outcome absent/present). In their design, Melchers et al. (2006) included an individual cue F that was followed by no change (F0) in their unidirectional outcome group but by a reduction in hormone level (F-) in their bidirectional outcome group. Another aim of our study was to test whether giving such direct experience with a reduction in hormone level was critical to establish the bidirectional nature of the outcome, or whether simply instructing participants that it could change in either direction would be sufficient. Therefore, we included a similar cue I in our training phase, which we labelled a "reference" cue, and followed it by no change in hormone level in one group (the No Reference Group) and by a reduction in hormone level in a second group (Reference group). In our experiment, however, both groups were instructed that the outcome was bidirectional and could increase, stay the same or decrease after a meal. Apart from the reference cue I, participants were exposed to a range of food cues A-H that followed the same design as in our previous experiments on prevention learning (e.g., Lee & Lovibond, 2021) and implemented an A+/ negative discrimination in addition to training a control cue D and filler cues (see Table 1). These cues were all followed by a hormone increase or no change. After the training phase, participants were asked to make predictions about novel compounds in which a separately trained excitor C was combined with the feature B, as well as with a control cue D (summation test). This comparison assessed the transfer of B's properties from the training excitor A to the test excitor C, relative to the control cue D. We hypothesised that participants in the Reference group would show a larger difference in CB vs CD ratings, as well as more negative prediction ratings to B alone, compared to participants who only ever saw an increase in hormone levels. Table 1 Procedure of Experiment 1. TRAINING TEST PREDICTIONS CAUSAL RATINGS OPEN-ENDED QUESTION FORCED-CHOICE CAUSAL STRUCTURE ASSESSMENT A+ AB0 A AB B A B B B C+ C CB CD CI C DE0 DE D E D E F0 GH+ F F I0/ J I J Note: + = an increase in hormone level, 0 = no change, and - = a decrease. Our previous work on feature negative learning in causal judgment with unidirectional outcomes suggested that humans infer different causal structures about the feature B in a FN discrimination, regardless of whether AB was presented simultaneously or serially. Some participants reported that B directly prevents the outcome (Direct Prevention), consistent with the RW conception of prevention learning, whereas others reported the role of B as determining whether the causal cue A will cause the outcome to occur (Modulation), much like the modulatory role of a negative occasion setter (Lee & Lovibond, 2021). A third group of participants reported learning only about which outcome will occur with each combination of stimuli (Configural). Importantly, we found corresponding differences in transfer of B's inhibitory properties to the test excitor C, where participants in the Direct Prevention subgroup provided the greatest transfer (lowest prediction ratings to the CB compound compared to control compound CD), Configural participants showed the least amount of transfer, and Modulation participants were in between the two (see also Glautier & Brudan, 2019). In the present experiment, where the outcome was bidirectional, we predicted that some participants would infer a fourth causal structure, namely an Opposite Causal structure. In order to differentiate between empirical and theoretical aspects in this paper, we will use capital letters when referring to empirical data involving subgroup categories (e.g., Opposite Causal) and lowercase letters for the abstract theoretical causal structures. In this study, we predicted that not only would there be more participants in the Reference group who reported an Opposite Causal structure compared to the No Reference group, but this subgroup of participants would also show strongest transfer compared to all other subgroups, indexed by greater difference in ratings for CB relative to CD. Our rationale here was that Opposite Causal participants would be more confident in predicting transfer since they construed the feature as directly causing the opposite effect to the test excitor, where the similarity of A and C should not matter. The Reference group experienced cue I paired with a decrease in hormone level (I-), whereas the No Reference group experienced cue I paired with no change in hormone level (I0). Column headings describe each phase of the experiment in sequence from left to right, beginning with the Training phase and ending with the Forced-choice causal structure assessment. All stimuli presented in each phase (and their associated outcomes) are denoted below the relevant column heading. Method Participants One-hundred and eighty nine participants recruited through Prolific (64 female, Mage = 30.3, SD = 10.4) participated in this study in exchange for monetary payment (20min at PS6GBP/hr). Apparatus & Stimuli The experiment was programmed using the jsPsych library (de Leeuw, 2015). Cue stimuli, which included the image of the food and a text description, were presented on a blank background that was 300 pixels wide by 300 pixels high. A total of 10 experimental cues were used in this study (cues A-J); the assignment of cues was randomised across participants. Outcome stimuli consisted of a verbal description of the change in hormone level (e.g. hormone level: no change) in bold text. Outcome stimuli were presented on a blank background 609 pixels wide and 300 pixels high. Procedure The task procedure reported here followed previous work from our lab (Lee & Lovibond, 2021; Chow, Lee & Lovibond, 2022), apart from the bidirectional nature of the outcome and the prediction scale. Training phase Participants were asked to imagine they were a doctor investigating which foods were causing fluctuations in hormone level in "Mr X". Participants were told that excessive levels of the hormone are linked to a particular disease, and changes in hormone level are thought to be related to diet. On each trial, participants were shown different meals that Mr X had eaten, and asked to predict whether Mr X's hormone level would increase, decrease, or experience no change after eating that meal. Predictions were made on a scale from "Definitely DECREASE" to "Definitely INCREASE", with a midpoint of "No Change". Ratings were recorded on a bidirectional numerical scale from -100 to +100. Once participants had made a prediction, the "Continue" button appeared at the bottom of the scale and they were able to continue to the next screen. The prediction scale was then replaced with outcome feedback in text (hormone level increase, decrease or no change), which remained on screen for 2 seconds before a 2-second intertrial interval where all cues disappeared from the screen. Training trials consisted of 3 blocks with 2 presentations of each trial type in each block (see Table 1). The order of presentation for compound cues was counterbalanced within-block (e.g. AB and BA), such that participants saw both orders of presentation in a randomised order (AB first or BA first). Trial types were also randomised in a way that participants never saw two identical trials presented successively. In total, participants completed 42 training trials with 6 presentations of each trial type. Outcome prediction at test After completing the training phase, participants were asked to continue making predictions about changes in Mr X's hormone level, but were told they would no longer be presented with feedback. The prediction scale used in this phase was identical to that presented during training. Participants were shown summation compounds consisting of the separately trained excitor C with the trained inhibitor B (CB), control cue D (CD), and reference cue I (CI), as well as familiar cues from the previous phase (A-I) and a novel cue J. Each trial type was presented twice, and the left-to-right order of presentation for compounds cues was again counterbalanced. Causal ratings Following the test predictions, participants were given instructions about the causal judgement phase of the study. They were asked to rate the extent to which they thought different foods caused or prevented an increase in hormone level in Mr X. Participants were informed that the rating scale in this phase was different to the prediction scale they had seen in previous phases. The causal rating scale ranged from "Strongly PREVENTED an increase" to "Strongly "CAUSED an increase" with a midpoint of "No effect". These ratings were recorded on a bidirectional numerical scale from -100 to +100. The wording of the causal rating question was chosen to match that used in our previous studies on feature negative learning with unidirectional outcomes (e.g., Lee & Lovibond, 2021), and also so that it would be consistent with any of the hypothesised causal structures. Open ended question After completing the causal judgement phase, participants were asked a single open-ended question about the critical cue B. Participants were shown an image of cue B at the top of the screen, followed by a text field box where they could explain what they had learned about the role of cue B. Participants were encouraged not to leave the field box empty. Causal structure assessment In the final phase of the study, participants were asked to assess the role of cue B in a 4-alternative forced-choice (4AFC) question. An image of cue B was presented at the top of the screen, and participants were asked to select the option that best described what they thought about the role of cue B. Three of the options were similar to those used in Lee & Lovibond (2021), Lovibond & Lee (2021) and Chow, Lee & Lovibond (2022). Specifically, the Modulation option was "It prevented an increase in hormone level caused by specific foods", the Direct Prevention option was "It prevented an increase in hormone level in general", and the Configural option was "It is hard to know the exact role of individuals foods such as this one. I concentrated on remembering which combinations of foods caused changes in hormone level and worked from there". In addition, we included a fourth option to capture an opposite causal structure, where cue B is thought to produce the outcome in the opposite direction (i.e. hormone decrease). The phrasing of the Opposite Causal option was "It caused a decrease in hormone level". The order of presentation of the four options was randomised between participants. After making a selection, participants could proceed to the final screen where they were asked if they had written anything down during the course of the experiment. Participants were encouraged to provide an honest response and were told that their response would not affect their eligibility to be paid. Statistical analysis The primary measure of interest was the outcome prediction ratings for summation compounds CB and CD. To test these differences, and in particular whether they were systematic differences as a function of group, we analysed the data with three orthogonal contrasts using the afex (Singmann et al., 2018) and emmeans (Lenth, 2019) packages in R. We compared 1) average ratings for compound CB compared to CD, 2) average ratings for participants in the Reference group compared to the No Reference group for compounds CB and CD, and 3) the interaction between these two contrasts. We also included simple effects to test the CB vs CD difference for the Reference group and the No Reference group separately. We also directly compared average ratings for the feature B for participants in the No Reference vs Reference group. For analysis of causal ratings, we compared ratings for cues B vs D (averaged over group), ratings for Reference vs No Reference group (averaged over cues B and D), and the interaction between the two contrasts. Data from the training phase were analysed with planned contrasts that tested 1) ratings for cues followed by hormone increase to those followed by no change common to both groups (common predictive vs non-predictive cues), 2) linear trend over the 6 presentations, 3) average ratings for Reference vs No Reference group, and 4) all interactions between these contrasts. Contrasts 2-4 were repeated for the comparison between reference cue I and common non-predictive cues. For all the contrasts described above, we also included a between-subject factor of inferred causal structure determined by participants response on the 4-AFC question. We tested two planned contrasts: 1) Opposite Causal compared to the average of all other subgroups, and 2) Configural subgroup compared to the average of the two inhibitory subgroups (Direct Prevention and Modulation). All contrasts were tested as main effects (averaged over all other factors), as well as in interaction with all contrasts on other factors. These contrasts were selected to compare the subgroup of participants who endorsed an Opposite Causal structure to all other subgroups, as this structure is novel to the present study. We have also previously found the Configural subgroup to produce qualitatively different pattern of results compared to Modulation and Prevention subgroups (Lee & Lovibond, 2021); this is tested in the second contrast. These participants tend to report only remembering the outcomes of the stimulus combinations and remain agnostic about the effects of B alone. The phrasing of the Configural option in the 4-AFC question also differed from the other options in that it did not involve making any inferences about the causal status of B, and was therefore the more conservative of the options. Thus, of the four causal structures assessed in this study, we predicted the strongest transfer in the Opposite Causal subgroup, and the weakest transfer in the Configural subgroup, with Modulation and Prevention subgroups in between. We did not include contrasts comparing the two inhibitory subgroups in the present study as we have previously argued that differences between participants who report a Direct Prevention and Modulation causal structure does not reflect qualitative differences in what is inferred, but rather quantitative differences in their willingness to generalise properties of the feature B to a novel test excitor (Chow, Lee & Lovibond, 2022). Finally, we also included a chi-square test of independence to compare participants' causal structure selection as a function of group to determine whether direct experience with a negative outcome influenced the proportion of participants who inferred an opposite excitatory causal structure to B. The full dataset for the two experiments reported here is publicly available at the Open Science Framework, and can be accessed at Results To recap our specific hypotheses for this experiment, we predicted that more participants would report an Opposite Causal structure in the Reference group, where they were explicitly presented with a cue that led to hormone level decrease, compared to the No Reference group. We additionally predicted that Opposite Causal participants would show greatest transfer in a summation test, indexed by greater difference in prediction ratings for CB compared to CD, as well as more negative prediction ratings to B alone, compared to all other subgroups. For brevity, figures presented on all test measures only include the primary cues of interest. For participants' ratings on all stimuli presented at test, see online Supplemental Materials. Exclusion criteria As in our previous published studies (Lee & Lovibond, 2021; Lovibond & Lee, 2021; Chow, Lee & Lovibond, 2022), participants' data were excluded from analysis if they reported writing down information during the task or if they failed to meet the training criterion. To pass the training criterion, all participants were required to provide 1) average rating > 75 for positive predictive cues and, 2) average rating between -25 and 25 for non-predictive cues. Participants in the Reference group were additionally required to provide an average rating < -75 for the reference cue I (cue I was a non-predictive cue in the No Reference group). In addition to the two criteria described above, participants were also presented with an instruction check prior to starting the task (see Supplemental Materials for the exact wording). Failure to provide a correct response on all three questions resulted in the program restarting at the first instruction screen. Participants who failed this instruction check more than twice (instructions were repeated at least three times) were excluded from analysis. Of the 189 participants recruited, 17 participants admitted to writing something down during the study, an additional 11 further participants failed the instruction check, and an additional 20 failed to meet the training criterion. After applying all three exclusions, 141 eligible datasets remained; 71 datasets from participants in the No Reference group, and 70 datasets from participants in the Reference group. Causal structure assessment For consistency with previous published studies from our lab, we defined subgroups based on participants' forced choice causal structure selection and not their open-ended responses. A breakdown of subgroup categorisation for participants in the No Reference and Reference groups is shown in Table 2. Although there were some differences between the groups in the pattern of causal structure choices, a chi-squared test of independence showed no statistical difference in reported causal structure as a function of group, c2 (3) = 6.37, p = .095. Thus, contrary to our hypothesis, we found no significant difference in the proportion of participants reporting an Opposite Causal structure as a function of group. Table 2 Number of participants in each group as a function of their 4-AFC selection. GROUP CAUSAL STRUCTURE NUMBER OF PARTICIPANTS No Reference Configural 20 Modulation 23 Opposite Causal 19 Prevention 9 Reference Configural 28 Modulation 19 Opposite Causal 9 Prevention 14 Training Figure 2 shows participants' average predictions across the six presentations of each trial type, separated by group. Analysis of training predictions showed a significant overall effect of cue type comparing common predictive to non-predictive cues, F(1,133) = 1487, p < .001, ep2 = .918, that also interacted with linear trend of presentation, F(1,133) = 423.3, p < .001, ep2 = .761. These findings suggest that participants successfully learned over trials which cues were predictive of an increase in hormone level, and which cues produced no change. Importantly there was no significant interaction with group, F(1,133) = 1.46, p = .228, ep2 = .011; learning for the common predictive and non-predictive cues progressed similarly for the two groups. Comparison of ratings for the reference cue I compared to the non-predictive cues showed a main effect of cue type, F(1,133) = 405.7, p < .001, ep2 = .753, which interacted significantly with linear trend of presentation, F(1,133) = 77.8, p < .001, ep2 = .369. Importantly we also found a three-way interaction between cue type, linear trend and group, F(1,133) = 65.3, p < .001, ep2 = .329, confirming that learning about the reference cue progressed differently for the two groups, with participants in the Reference group successfully learning across successive trials that cue I predicted a decrease in hormone level. Figure 2 Mean Outcome Prediction (+-SE) During Training For Participants In No Reference And Reference Group In Experiment 1. Note: Filled symbols denote stimuli that predicted hormone level increase, and unfilled symbols denote stimuli that predicted no change (or hormone level decrease in the case of cue I in the Reference condition). Mean Outcome Prediction (+-SE) During Training For Participants In No Reference And Reference Group In Experiment 1 Causal structure comparisons in the Training phase revealed only a marginally significant interaction that reflected slightly stronger discrimination between the common predictive and non-predictive cues in the Opposite Causal subgroup compared to the other three subgroups, F(1,133) = 5.03, p = .027, ep2 = .036. No other main effects or interactions were significant, Fs < 1. Training data broken down by causal structure subgroup can be found in Supplemental Materials. Outcome prediction at test Each participant's test predictions were averaged across the two presentations for each trial type. Figure 3 shows the mean outcome predictions for primary stimuli of interest, B, CB, CD, CI, and I, separated by group (3a) and broken down by causal structure subgroups (3b). We were primarily interested in participants' ratings for summation compounds CB and CD, as well as test predictions for B alone. Comparison of participants' ratings to cue I alone were also included as a manipulation check. Figure 3 Average Outcome Prediction at Test (+-SE) for Critical Summation Compounds (a) as a Group Average, and (b) Separated by Causal Structure Subgroup, for the No Reference and Reference Group Respectively in Experiment 1. Average Outcome Prediction at Test (+-SE) for Critical Summation Compounds (a) as a Group Average, and (b) Separated by Causal Structure Subgroup, for the No Reference and Reference Group Respectively in Experiment 1 Contrasts comparing CB and CD ratings showed a main effect of cue, F(1,133) = 43.2, p < .001, ep2 = .245, which also interacted significantly with group, F(1,133) = 7.17, p = .008, ep2 = .051. These results indicate that overall, participants showed successful transfer of B's properties from A to C, and the CB-CD difference was greater for participants who saw a reference cue leading to hormone decrease than for those who never saw hormone decrease as an outcome. There was no main effect of group, F < 1. Importantly, we found the CB-CD difference to interact with causal structure, in particular when comparing the Opposite Causal subgroup to all other subgroups, F(1,133) = 8.68, p = .004, ep2 = .061. As hypothesised, the Opposite Causal subgroup showed more suppressed ratings to CB compared to CD relative to the other subgroups. Importantly, there were no further interaction with group as a factor, suggesting that individual differences in transfer as a function of inferred causal structure were insensitive to the reference cue manipulation. No other contrasts were significant, largest F(1,133) = 2.03, p = .157, ep2 = .015 (see Supplemental Materials for additional results involving subgroup contrasts). A similar comparison of ratings to B alone at test showed a main effect of group, F(1,133) = 24.1, p < .001, ep2 = .154, with lower predictive ratings in the Reference group than No Reference group. There was also a causal structure difference when we compared the Opposite Causal subgroup to all other subgroups, F(1,133) = 19.4, p < .001, ep2 = .127. No other contrasts or interaction involving causal structure subgroup was significant, Fs < 1. Together, these results show that participants who saw a separate cue that caused a decrease in hormone level were more likely to predict that B alone would result in hormone decrease than participants who never experienced hormone decrease as an outcome. Furthermore, as we hypothesised, participants who inferred an Opposite Causal structure were also more likely to predict hormone level decrease in the presence of B alone, and showed greater transfer of B's properties in a summation test. Critically, however, the effect of direct experience with a negative outcome and causal structure were additive, as we found no interaction between causal structure and group. Unsurprisingly, analysis of ratings to cue I alone showed a main effect of group, F(1,133) = 1144.7, p < .001, ep2 = .898, with lower ratings in the Reference group than the No Reference group. No other contrasts tested were significant, largest F(1,133) = 2.27, p = .135, ep2 = .017. Causal ratings Figure 4 illustrates causal ratings for cues B, D and I, for each of the groups separately (4a) and separated by causal structure subgroup (4b). This test differed from the outcome prediction test in that participants were asked to rate the ability for each individual cue to cause or prevent the outcome from occurring. Figure 4 Mean Causal Ratings at Test (+-SE) for Critical Stimuli Only for Participants in the No Reference and Reference Group as a (a) Group Mean, and (b) Separated By Causal Structure in Experiment 1. Note: Causal ratings were made on cause-prevent scale, from -100 (Strongly prevented an increase) to +100 (Strongly caused an increase) with a midpoint of 0 (No effect). Mean Causal Ratings at Test (+-SE) for Critical Stimuli Only for Participants in the No Reference and Reference Group as a (a) Group Mean, and (b) Separated By Causal Structure in Experiment 1 Comparison of mean ratings for cues B and D revealed a main effect of cue, F(1,133) = 51.7, p < .001, ep2 = .280, with more negative (preventive) ratings for B relative to D averaged across groups. There was no main effect of group, and no interaction between group and cue, Fs < 1. Contrasts comparing the different causal structure subgroups revealed a small but significant difference in mean ratings for the Opposite Causal subgroup relative to all other subgroups (averaged over cues B and D), F(1,133) = 4.72, p = .032, ep2 = .034, and an interaction between this comparison and cue type (B vs D), F(1,133) = 5.27, p = .023, ep2 = .038. No other causal structure interactions were significant, largest F(1,133) = .923, p = .657, ep2 = .001. Together these results suggest some differences as a function of inferred causal structure on ratings of B's ability to prevent the outcome--the difference in causal ratings to B compared to D was significantly greater for Opposite Causal compared to all others subgroups. These findings did not appear to differ statistically as a function of group. Analysis of participants' ratings for cue I revealed lower (more preventive) ratings in the Reference group compared to the No reference group, F(1,133) = 102.9, p < .001, ep2 = .436, and higher ratings for the configural subgroup compared to the average of the two inhibitory subgroups, F(1,133) = 13.2, p < .001, ep2 = .090. No other comparisons were statistically significant, Fs < 1. Discussion Experiment 1 showed that when the feature B in an A+/ discrimination was presented in compound with the predictive cue C at test, ratings were lower compared to when C was paired with a control cue, D. This difference in summation test ratings was greater when participants had direct experience with a separate cue that led to a decrease in hormone level (Reference group), compared to those who had never seen a negative outcome (No Reference group). Participants in the Reference group were also more likely to predict a decrease in hormone level when cue B was presented alone compared to participants in the No Reference group. However, we did not find the same difference between groups on causal ratings for cue B relative to cue D. We also did not find a difference in the proportion of participants reporting each causal structure as a function of group. Thus, although experience with hormone level decrease produced stronger transfer effects in the summation test, direct experience with a negative outcome was not necessary for participants to infer an opposite excitatory causal structure for B. A possible reason for this result is that simply presenting a bidirectional prediction scale was sufficient to encourage some participants to consider that certain foods might lead to a decrease in hormone level, even if they had no direct evidence of this in the experiment. This suggests that the inclination for some participants to infer an opposite causal structure in a FN discrimination might be greater than previously expected. Contrasts comparing the different causal structure subgroups also showed differences in summation test ratings as a function of self-reported causal structure for cue B. As predicted, we found greater transfer for participants who endorsed an Opposite Causal structure compared to all other subgroups in the summation test. Participants who reported an Opposite Causal structure also provided more negative prediction ratings to cue B compared to all other subgroups, suggesting that participants who inferred an opposite generative relationship between B and the outcome were more likely to predict a decrease in hormone levels in the presence of B alone, and to show greater transfer of B's properties to a novel causal cue. Together these results show that when the outcome has the potential to be negative, some participants infer an opposite causal relationship between the negative feature and the outcome, and this type of learning is distinct from prevention and modulatory learning. In summary, in addition to the causal structures we have investigated in our previous work, Experiment 1 provided initial evidence for a possible fourth causal structure inferred by participants in a FN discrimination when the outcome is bidirectional. Importantly, these results are the first to show that strong transfer in a summation test and negative prediction ratings to the feature alone when a bidirectional outcome is used are largely driven by participants who inferred an opposite excitatory causal structure to B (B causes a decrease in hormone levels) rather than direct prevention learning as previously proposed (B prevents hormone levels from increasing). The possibility of a negative outcome seems to allow participants to infer an opposite excitatory causal structure for B whereby it is seen as directly causing a decrease in outcome level. Experiment 2 If our conception of an opposite causal structure is correct, then participants who endorse this structure should treat the feature as equivalent to a cue that has been explicitly trained to predict a reduction in the outcome. In Experiment 2, we tested this proposition by examining the degree to which the feature would block learning about a novel cue that was directly paired with a decrease in hormone level. The blocking procedure is commonly used in the associative learning literature to study the effects of cue competition (Kamin, 1969). The idea here is that humans and animals judge the causal relationship between two events by considering other potential causal cues in the environment, and all cues present concurrently compete for predictive value. When an outcome is already well predicted by a cue, for example if participants already expect hormone levels to decrease in the presence of B, learning about the predictive significance of another cue present at the same time is impaired. In this study, the feature was first presented in a FN discrimination like in Experiment 1. Then, in a Blocking phase, the feature B was presented in compound with a novel cue (X) and the compound was followed by a decrease in hormone level (BX-). We hypothesised that participants who had inferred an opposite causal structure for B would show greater blocking of X compared to a control cue Y that was also novel in phase 2 and followed by the same decrease in hormone level but whose partner cue was never part of a FN discrimination (DY-). This is because these participants should learn that B alone will cause a hormone level decrease, which should effectively compete with the novel cue X for association with the observed decrease in hormone level. In other words, when BX is presented with hormone level decrease, the outcome is not surprising and learning about X is blocked. In contrast, the genuinely inhibitory structures (direct prevention, modulation) would not be expected to support strong blocking. In the case of modulation, participants are thought to learn that the feature B modulates the relationship between the training excitor A and an increase in hormone level, which is not directly relevant to the Blocking manipulation. Indeed, a modulator should make no assumption about the ability for B to be active by itself without an excitor present. In the case of direct prevention, participants are thought to learn that the feature prevents the outcome produced by the training excitor A (hormone level increase), therefore a preventer might learn that B alone would lead to no change in hormone levels, since B prevents hormone levels from increasing. When presented with the BX compound for the first time, the outcome (hormone level decrease) should be surprising since it is not predicted by the presence of B or X, and the cues compete equally for association. Thus, we expected to find greater evidence of blocking to X in the Opposite Causal subgroup relative to all other subgroups. The design of Experiment 2 is shown in Table 3. Participants were presented with a similar predictive learning task to Experiment 1, with foods as cues and changes in hormone level as the outcome. The hormone level could again increase, decrease or stay the same on each trial. However, unlike in Experiment 1, hormone level changes were presented as numeric values. A feature negative contingency was set up such that cue A reliably predicted an increase in hormone level by 20 units (A+20), and simultaneous presentation of cues A and B resulted in no change in hormone level (AB0). To enhance transfer of inhibition, all participants were presented with a reference cue that predicted a decrease in hormone level by 20 units (C-20). This reference cue was also used in a comparison to B at test in order to determine if participants treated B in the same way as a cue that was directly paired with a reduction in hormone level, which we predict might be the case for participants who endorse an Opposite Causal structure. DE was included to provide a control stimulus for feature B, where cue D was similarly presented in compound with another cue and that the compound was always followed by no change in hormone level (DE0). Cue F was included as a filler cue (F0) to prevent participants from learning that all single cues led to some change in hormone level. A critical difference in the training phase of Experiment 2 compared to Experiment 1 was the inclusion of an additivity design, where cues G and H individually predicted an increase in hormone level by 20 units (G+20, H+20), and GH in compound predicted an even larger increase in hormone level of 40 units (GH+40). The inclusion of a magnitude additivity manipulation has previously been shown to enhance blocking (Lovibond, Been, Mitchell, Bouton & Frohardt, 2003; see also De Houwer, Beckers & Glautier, 2002). In the Blocking phase of the experiment, two new compounds BX and DY, both predicting -20 hormone level change, were introduced. We also included three familiar cues from the training phase (F0, G+20, GH+40) to maintain continuity between the two phases. Throughout both the Training and Blocking phases, cues B and D received identical training histories, and differed only as a function of whether they were part of a FN discrimination. Similarly, cues X and Y were both novel in the blocking phase of the study and were presented in compound with another familiar cue; both compounds were paired with a decrease in hormone level of the same magnitude. Table 3 Design of Experiment 2. TRAINING BLOCKING PHASE TEST PREDICTIONS CAUSAL RATINGS FORCED-CHOICE CAUSAL STRUCTURE ASSESSMENT A+20 AB0 BX-20 A B AB A B B C-20 DY-20 C C DE0 DE D E D E F0 F0 G+20 H+20 G+20 G GH G H GH+40 GH+40 I X Y I X Y Note: + = an increase in hormone level, 0 = no change, and - = a decrease. Numeric values indicate the magnitude of change. Column headings describe each phase of the experiment in sequence from left to right, beginning with the Training phase and ending with the Forced-choice causal structure assessment. All stimuli presented in each phase (and their associated outcomes) are denoted below the relevant column heading. At test, we assessed predictive ratings for cues X and Y individually. If participants inferred an Opposite Causal structure for B, they might determine from training that B alone produced a -20 change in hormone level. A consequence of this inference is that when participants were subsequently presented with BX leading to -20 hormone level change, they would be able to infer that X had no additional impact on hormone level. In contrast, we expected greater learning about Y since D had not already been established as a predictor of hormone decrease. As a result, we would expect greater blocking, indexed by less negative ratings to X compared to Y, in the Opposite Causal subgroup compared to participants in all other subgroups. We additionally predicted that participants in the Opposite Causal subgroup would provide similar ratings to B and to C, a cue that had been presented alone and predicted a -20 change in hormone levels. Method Participants One-hundred and fifty participants recruited through Prolific (91 female, Mage = 24.8, SD = 6.23) participated in this study in exchange for monetary payment (20 min at PS6GBP/hr). Apparatus & Stimuli A total of 11 cues were presented in this study, labelled as A-I, X and Y. X and Y were novel cues presented in the second phase of training as part of the blocking manipulation. Presentation of stimuli in this study was identical to that in Experiment 1, with the exception of the outcomes. Outcomes presented in this study consisted of numeric values from -20 to +40 in 20-point increments. Positive and negative signs were included to denote increases and decreases in hormone levels respectively (e.g. hormone level: +20). When there was no change in hormone level, a verbal description of the outcome was also presented in text below the numeric value . Figure 5 Example Screenshots from a Single Training Trial in Experiment 2, Where the Cue is Followed by No Change in Hormone Level. Example Screenshots from a Single Training Trial in Experiment 2, Where the Cue is Followed by No Change in Hormone Level Procedure The method used in this experiment was largely similar to Experiment 1 with the exception of an additional blocking phase. In the blocking phase, two novel compounds BX and DY were presented for the first time, both of which were followed by an outcome of -20. X and Y were also presented in test predictions and causal ratings at test. In the interest of saving time, we removed the open-ended assessment for B that was presented in Experiment 1. Another point of difference between this experiment and Experiment 1 was the outcome prediction scale presented on each trial and in the test predictions. In this study, predictions were made on a scale from DECREASE to INCREASE with a mid-point of NO CHANGE. Numeric markers were also included on the scale from -40 to +40 with a mid-point of 0 aligning with the text description NO CHANGE. However, the extremes of the scale did not have a numeric value; this was to illustrate that the hormone level could decrease or increase by an indefinite value, and thereby avoid floor and ceiling effects (see De Houwer et al., 2002). Numeric markers were included to ensure that participants were learning the cue-outcome associations appropriately and made predictions that were consistent with outcomes they had been presented with. In both the Training and Blocking phase of the study, feedback on the change in hormone level was provided on each trial after participants had made a prediction. No feedback was provided at test, consistent with Experiment 1. Statistical Analyses In this experiment, we were primarily interested in the magnitude of the blocking effect determined by participants' ratings to cue X compared to cue Y on both outcome predictions at test and causal ratings. Note that lower ratings to Y compared to X are indicative of greater blocking to X. We also compared participants' ratings for cue B alone relative to the control cue D, as well as to the directly trained cue C, as a function of their reported causal structure subgroup in both outcome test predictions and causal ratings. Predictive ratings from the training phase were analysed using planned within-subject contrasts that tested average ratings for 1) stimuli that predicted a +20 outcome increase (G, H and A) compared to no change (AB and DE; +20 vs 0), 2) the stimulus predicting a +40 outcome increase (GH) vs the average of standard predictive cues (40 vs +20), 3) stimuli followed by no change compared to stimulus C which was followed by hormone level decrease (0 vs -20), 4) linear trend over six presentations, and 5) the interactions between contrasts 1-3 and linear trend of presentation. A similar set of contrasts was tested in the blocking phase, in addition to a comparison of participants' ratings to BX and DY on the first trial of the blocking phase (prior to any feedback). For all contrasts described above, we also tested the interaction with causal structure subgroup using the same between-subjects contrasts as Experiment 1. Results Exclusion criteria The same exclusion criteria were used in this study as in Experiment 1. Of the 150 participants who completed the study, 11 were excluded for writing down information during the experiment, 5 were excluded for failing the instruction check more than twice, and an additional 16 participant was excluded for failing to meet the training criterion. After applying all the exclusions, 118 participants remained. Causal structure assessment Based on participants' responses on the 4AFC question, we had 37 participants reporting a Configural structure, 22 reporting a Modulation structure, 23 reporting a Direct Prevention causal structure, and 36 reporting an Opposite Causal structure. Training Figure 6a illustrates mean prediction ratings across each presentation of the different trial types presented in the training phase average across all participants. No main effect or interaction contrasts involving causal structure were significant on this measure, all Fs < 1. Analysis of stimuli predicting hormone level +20 compared to stimuli predicting no change showed a main effect of cue type, F(1,114) = 1849, p < .001, ep2 = .942, which interacted significantly with linear trend of presentation, F(1,114) = 259.3, p < .001, ep2 = .695. Similarly, there was a significant main effect of cue type when comparing standard predictive (+20) to the additivity predictive cues (+40), F(1,114) = 1417, p < .001, ep2 = .926; this also interacted significantly with linear trend of presentation, F(1,114) = 7.46, p = .007, ep2 = .061. Finally we found a main effect of cue type comparing stimuli leading to no change versus the reference cue C that predicted a decrease in hormone level (0 vs -20), F(1,114) = 948.5, p < .001, ep2 = .893, which also interacted with linear trend of presentation, F(1,114) = 59.6, p < .001, ep2 = .343. There was no main effect of linear trend, F(1,114) = 1.53, p = .219, ep2 = .013. Overall, these results confirm that across the six presentations, participants learned which outcomes were associated with each trial type, and there were no differences in acquisition as a function of causal structure subgroup. Figure 6 Mean Outcome Prediction (+-SE) During (a) Training and (b) Blocking Phase in Experiment 2. Note: Filled symbols denote trials that were paired with a hormone level increase (e.g., G+20 and GH+40), and unfilled symbols denote trials that were followed by no change (F0) or by a hormone level decrease (e.g., BX-20 and DY-20). Mean Outcome Prediction (+-SE) During (a) Training and (b) Blocking Phase in Experiment 2 Blocking phase Figure 6b illustrates participants' mean outcome predictions across six presentations of each trial type collapsed across causal structure subgroups. Contrasts comparing standard predictive cue, G+20, to the cue that was followed by no change (F0), revealed a main effect of cue type, F(1,114) = 4146, p < .001, ep2 = .973. There was also a main effect of cue type when we compared standard vs additivity predictive cues (G+20 vs GH+40), F(1,114) = 19909, p < .001, ep2 = .994, and when we compared the non-predictive cue to the blocked cues (0 vs -20), F(1,114) = 1420, p < .001, ep2 = .926. The effect of 0 vs -20 interacted significantly with linear trend across trials, F(1,114) = 148.9, p < .001, ep2 = .566. There was also an overall linear trend, F(1,114) = 117.2, p < .001, ep2 = .507, driven by the sharp decrease in ratings for cues BX and DY across trials. No other interaction contrasts, including main effect and interaction contrasts involving causal structure subgroups, reached statistical significance, largest F(1,114) = 1.71, p = .194, ep2 = .015. Analysis of participants' first rating on BX and DY trials revealed an overall main effect of cue type, F(1,114) = 15.6, p < .001, ep2 = .120, driven by higher ratings to DY than BX. However, this difference did not interact with any of the causal structure comparisons. Ratings in the Blocking phase broken down by causal structure subgroup can be found in Supplemental Materials. No other main effects or interactions were significant, Fs < 1. Outcome prediction at test Participants' test predictions were averaged across the two presentations of each trial type. Figure 7 illustrates the mean outcome predictions for the cues of interest and their relevant controls, B, C, D, X and Y, averaged across all participants (7a) and separated by causal structure subgroup (7b). We were primarily interested in whether Opposite Causal participants show greater blocking of X relative to Y, indexed by less negative ratings to X, compared to all other subgroups. We additionally predicted that this subgroup of participants would provide equivalent (negative) prediction ratings to B alone and to a cue that directly predicted hormone level -20. Figure 7 Average Outcome Prediction at Test (+-SE) For Critical Stimuli (a) as a Group Average, and (b) Separated By Causal Structure Subgroup in Experiment 2. Average Outcome Prediction at Test (+-SE) For Critical Stimuli (a) as a Group Average, and (b) Separated By Causal Structure Subgroup in Experiment 2 The comparison of ratings for X and Y showed a main effect of cue type, F(1,114) = 6.45, p = .012, ep2 = .054, with more negative ratings to Y relative to X. This is evidence of an overall blocking effect. There was also an interaction between cue type (X vs Y) and the contrast comparing Opposite Causal to all other subgroups, F(1,114) = 5.27, p = .023, ep2 = .044, indicative of a greater blocking effect in the Opposite Causal subgroup. No other main effects or interactions involving causal structure subgroup were significant, largest F(1,114) = 1.31, p = .256, ep2 = .011. Simple effects comparing the difference in ratings to X and Y for the Opposite Causal subgroup only showed a significant effect of cue type, F(1,35) = 19.1, p < .001, ep2 = .353. Comparison of participants' ratings to B relative to D also showed an overall effect of cue type, F(1,114) = 40.3, p < .001, ep2 = .261, which interacted significantly with causal structure contrasts comparing Opposite Causal to all other subgroups, F(1,114) = 26.7, p < .001, ep2 = .189. These results are similar to the finding from Experiment 1 that the Opposite Causal subgroup showed a stronger prediction that B would decrease hormone level compared to the other subgroups. Similarly, comparison of prediction ratings to B vs C, a cue which was presented alone followed by -20 hormone level, revealed a significant main effect of cue type, F(1,114) = 59.5, p < .001, ep2 = .343, and a significant interaction with causal structure contrasts comparing Opposite Causal to all other subgroups, F(1,114) = 14.9, p < .001, ep2 = .116. These results suggest that ratings to B were more similar to C for the Opposite Causal participants compared to all other subgroups. We additionally found significant main effect contrasts where Opposite Causal participants gave significantly lower ratings compared to all other subgroups collapsed across cues B and C, F(1,114) = 22.9, p < .001, ep2 = .167. Simple effects comparing ratings to B vs C for the Opposite Causal subgroup alone also showed no significant difference between ratings for the two cues, F(1,114) = .780, p = .379, ep2 = .007. Together, these results suggest that ratings to B were much more negative, and were in fact equivalent to ratings to C, for participants in the Opposite Causal subgroup compared to all other subgroups; these results are consistent with our predictions. Finally, participants in the Configural subgroup also gave significantly less negative ratings compared to all other subgroups averaged across both cues, F(1,114) = 10.4, p = .002, ep2 = .084. No other analysis involving causal structure subgroup was significant, F < 1. Causal ratings Mean causal ratings for cues B, C, D, X and Y are shown in Figure 8 as a group average (8a) and separated by causal structure subgroups (8b). Consistent with the outcome prediction ratings, analysis of causal ratings for X and Y showed a main effect of cue, F(1,114) = 6.07, p = .015, ep2 = .050, which interacted significantly with the contrast comparing Opposite Causal to all other subgroups, F(1,114) = 4.53, p = .035, ep2 = .038. This finding confirms stronger blocking of learning that X predicted a decrease in hormone level. Simple effects comparing X and Y for the Opposite Causal subgroup only showed a significant difference in ratings, F(1,35) = 14.0, p < .001, ep2 = .286. No other main effects of interactions involving causal structure subgroups were significant, Fs < 1. Figure 8 Mean Causal Ratings at Test (+-SE) for Critical Cues (a) as a Group Average, and (b) Separated by Causal Structure Subgroup in Experiment 2. Mean Causal Ratings at Test (+-SE) for Critical Cues (a) as a Group Average, and (b) Separated by Causal Structure Subgroup in Experiment 2 Comparison of causal ratings to B vs D showed a similar pattern of results to the test predictions; there was a main effect of cue type, F(1,114) = 20.0, p < .001, ep2 = .149, which interacted significantly with contrasts comparing Opposite Causal to all other subgroups, F(1,114) = 8.72, p = .004, ep2 = .072. As in Experiment 1, the Opposite Causal subgroup gave stronger preventive ratings for B than the other subgroups. No other main effect or interactions involving causal structure contrasts were significant, largest F(1,114) = 2.41, p = .124, ep2 = .021. Similar comparison of causal ratings to B vs C produced the same pattern of results, with a main effect of cue type, F(1,114) = 40.8, p < .001, ep2 = .264, which interacted significantly with contrasts comparing Opposite Causal to all other subgroups, F(1,114) = 9.99, p = .002, ep2 = .008. No other main effects or interactions were significant, largest F(1,114) = 3.34, p = .070, ep2 = .028. Simple effects comparing ratings to B vs C for the Opposite Causal subgroup only revealed no significant difference in causal ratings to the two cues, F(1,114) = .586, p = .445, ep2 = .005. These findings present confirmatory evidence that participants who reported an Opposite Causal structure treated the feature B as equivalent to a cue that independently produced a decrease in hormone level. Importantly, this pattern of results was significantly different to all other subgroups, including the two inhibitory subgroups . Discussion The results from Experiment 2 extended the findings from Experiment 1 to a blocking manipulation, where the feature in a FN discrimination blocked learning of a novel cue paired with hormone level decrease in a subsequent phase. Outcome test predictions for X compared to Y revealed a significant overall blocking effect, with more negative ratings (indicating hormone level decrease) to the control cue than to the blocked cue. Importantly, the magnitude of the blocking effect was greater for participants who endorsed an Opposite Causal structure than for the other subgroups. These subgroup differences were also found when we compared predictions to B relative to D, with greater negative predictions to B in the Opposite Causal subgroup. This subgroup difference for B compared to D was also obtained in the causal ratings. We additionally showed that participants who reported an Opposite Causal structure gave ratings to B similar to those of a cue that directly led to a hormone level decrease (C-20). This is further evidence that when presented with a FN discrimination, some participants infer that B alone directly led to the opposite outcome, and treated B as equivalent to a cue that was explicitly paired with hormone level decrease. One potential criticism of the design of Experiment 2 is in the introduction of the additivity compound GH+40, where each element G and H were separately paired with an outcome of +20. The inclusion of this additivity compound might encourage participants to solve the FN discrimination by calculating the arithmetic difference between the outcome associated with A alone (+20) and the no change outcome on AB trials, which might then lead them to infer that B directly causes a decrease in hormone level. However, it should be noted that this arithmetic summation process is consistent with Melchers et al.'s (2006) argument that bidirectional outcomes mirror the symmetrical continuum of associative strengths assumed by the Rescorla-Wagner model, and should therefore encourage direct prevention learning. In contrast, our results suggest an alternative explanation that the discrepancy between A and AB trials encourages excitatory learning of B leading to the opposite outcome, indexed by the ability for B alone to generate predictions of hormone level decrease and block subsequent learning to X. General Discussion In this study, we were interested in testing the possibility that using bidirectional outcomes in an A+/ negative task allows participants to acquire an opposite excitatory causal structure to B that is distinct from known inhibitory structures like direct prevention and modulation. Both experiments showed that some participants inferred an Opposite Causal structure when presented with an outcome that could either increase or decrease. In Experiment 1, we showed that direct experience with a negative outcome was not necessary for participants to infer an Opposite Causal structure, nor did it lead to more participants reporting this causal structure to B. It appears that using an outcome that has the potential to vary in both directions is sufficient to lead some participants to the conclusion that the feature B directly causes a decrease in hormone levels, even without having seen a negative outcome. This finding poses a challenge for previous studies that have used the presence of a negative outcome (hormone level decrease) to differentiate between bidirectional and unidirectional outcomes, particularly when changes in hormone level were from an unspecified baseline (e.g., Melchers et al., 2006; Lotz & Lachnit, 2009; Baetu & Baker, 2010). It is plausible that in these studies, the manipulation used to establish outcome directionality was not effective, and that differences between groups at test were a product of extraneous factors, such as differences in the scales presented during training vs test (e.g., Baetu & Baker, 2010) or differences in scales presented for the unidirectional vs bidirectional outcome groups (e.g., Melchers et al., 2006; Lotz & Lachnit, 2009). We also found evidence of a subgroup difference in Experiment 1, where participants in the Opposite Causal subgroup showed the greatest transfer of B's properties to a novel cause in a summation test (i.e., greater CB-CD difference) compared to all other subgroups. We have previously proposed that inhibitory summation is best thought of as an instance of generalisation (Chow et al., 2022; see also Bonardi, Robinson & Jennings, 2017). Specifically, we suggested that in a FN discrimination task with unidirectional outcomes, individual differences in inhibitory transfer between Modulators and Preventers may not reflect qualitative differences in what is learned (i.e., occasion-setting vs direct prevention), but differences in participants' willingness to generalise inhibitory properties of the feature from training to test. In the present study, participants who endorsed an Opposite Causal structure were perhaps solving the FN discrimination differently to the Direct Prevention and Modulation subgroups. That is, they learned that B by itself directly produces a reduction in hormone level. This causal structure is straightforward to apply to a summation test since it does not involve generalisation--B's relationship with the outcome is independent of A. Thus, prediction ratings to CB are low since the expectation of hormone level increase in the presence of C is offset by the strong expectation of hormone level decrease to B, with minimal generalisation decrement in the summation test. The strong transfer seen among Opposite Causal participants together with strong preventative ratings to B alone in causal ratings compared to all other subgroups, provide further support that at least for some participants, causal learning about B with the opposite outcome has occurred. In Experiment 2, we found further evidence of opposite causal learning with bidirectional outcomes, where the feature was again inferred to cause a decrease in hormone levels. Presenting B together with a novel cue X successfully blocked learning that X predicted hormone level decrease when the compound was directly paired with a hormone level decrease. These findings are diagnostic of opposite causal learning to B since no additional information was provided by directly pairing B with hormone decrease, hence leading to blocking of learning to X. Causal and predictive ratings to B alone were also similar in magnitude to cue C, which had been explicitly paired with hormone level decrease. These results suggest that for participants in the Opposite Causal subgroup, the feature B was treated as equivalent to a cue that was active in producing a reduction in hormone levels by itself. These findings are in contrast to established theories of inhibitory learning which involve the suppression of the outcome elicited by a causal/excitatory cue, either by modulating the effect of the excitor or by directly preventing the outcome from occurring. Consistent with these accounts, inhibitors are typically thought to be behaviourally silent (Rescorla, 1969), with few demonstrations where the inhibitor directly elicits behaviour (but see Wasserman, Franklin & Hearst, 1974). In summary, our findings propose an alternative explanation to the idea proposed by Melchers et al (2006) that bidirectional outcomes in FN discrimination encourages direct prevention learning. We have shown that under these conditions, some participants are learning a generative causal relationship between the feature and the opposite outcome. This is distinct from an opposite inhibitory mechanism like the negative associative strength governing inhibition in the RW model, since in opposite causal learning the action of the feature is direct (i.e., does not require the presence of a background cause), and generative (does not involve the suppression of outcome activation). It is also important to note that the RW model in its original conception was designed to explain inhibitory learning with unidirectional outcomes, such as the presence or absence of a foot shock or food pellets in animal conditioning procedures. These outcomes may vary in magnitude, but they are unable to take on negative properties (i.e., anti-outcome). Thus, the model does not make any assumptions about the symmetry between the dimension of associative strength and the properties of the outcome, nor does it specify this as a requirement for the feature acquiring negative associative strength when an expected outcome is omitted. Importantly, any model that seeks to explain how inhibitory relationships are learned should not be limited to outcomes with a positive and negative dimension, but should account also for how we learn about discrete events where negative values are not possible. Indeed, it seems like there is nothing inherently special about a negative outcome that encourages learning distinct from that of causal learning in the positive direction. Negative outcomes are commonly used in human causal learning experiments, such as in a medical scenario where a drug cue is thought to lead to recovery from illness (e.g., Matute, Yarritu & Vadillo, 2011; Chow, Colagiuri & Livesey, 2019). These scenarios typically frame the relationship between treatment use and recovery as causal (treatment causes recovery); however recovery from illness may be more accurately construed as the reduction or termination of illness. Returning to the issue we began this paper with, what exactly are people learning when they experience a negative relationship? We have previously shown that there are substantial individual differences in human inhibitory learning using a feature negative arrangement with a unidirectional outcome (Lee & Lovibond, 2021; see also Glautier & Brudan, 2019). Additionally, we found that self-reported causal structure was predictive of the degree of transfer in a summation test. We have also suggested that differences in inhibitory transfer between Direct Prevention and Modulation subgroups is a result of differences in willingness to generalise inhibitory properties of the feature from training to test, rather than qualitative differences in what is learned (Chow et al., 2022). The novel contribution of the current paper is to present another possible causal structure in a FN procedure, which arises when a bidirectional outcome is used. We propose that rather than encouraging direct prevention (inhibitory) learning, as originally suggested by Melchers et al. (2006), bidirectional outcomes encourage at least some participants to learn an opposite excitatory causal structure. In our experiments, this subgroup of participants produced significantly different results to Configural, Direct Prevention and Modulation participants, showing greatest transfer in a summation test, greatest prediction of a decrease in hormone level when B was presented alone, and strongest blocking of a novel cue paired with a reduction in hormone level. Importantly, these participants did not report learning an inhibitory relationship between the feature and the outcome produced by the causal cue. Instead, they reported having formed a generative association between the feature and the opposite outcome. These findings suggest that evidence of a direct prevention structure is less prevalent than previously assumed. Together, these findings support our previous proposal that inhibitory learning in humans may perhaps be largely modulatory in nature (Lee & Lovibond, 2021). In conclusion, we propose an alternative to the claim that FN discrimination with a bidirectional outcome encourages direct prevention learning. We have shown that FN discrimination with a bidirectional outcome can be solved by assuming a causal relationship between the feature and the opposite outcome to that signalled by the partner cue during FN training. Together with previous findings that most participants infer a modulatory causal structure when solving a FN discrimination with unidirectional outcomes, we recommend that more attention be given to alternative mechanisms of prevention learning such as modulation. Data Accessibility Statement All data is made available on the Open Science Framework and can be accessed at None of the experiments were pre-registered. Additional File The additional file for this article can be found as follows: 10.5334/joc.266.s1 Supplemental Materials. Analyses and Figures. Ethics and Consent All reported experiments were approved by the University of New South Wales Human Research Ethics Advisory Panel C (approval number 3136). Participants provided online consent for their participation. Funding Information This study was funded by an Australian Research Council Discovery Project Grant [DP190103738] to Peter Lovibond. Jessica Lee was supported by a Discovery Early Career Researcher Award from the Australian Research Council [DE210100292]. Competing Interests The authors have no competing interests to declare. 1 Alloy, L. B., & Abramson, L. Y. (1979). Judgment of contingency in depressed and nondepressed students: Sadder but wiser? Journal of experimental psychology: General, 108 (4 ), 441. DOI: 10.1037/0096-3445.108.4.441 528910 2 Baetu, I., & Baker, A. G. (2010). 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PMC10000321 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1216 VoR Dr. Phil's Art Corner Happy Childhood Alexander Philip MD [email protected] 1 1 College Station, Texas, US CORRESPONDING AUTHOR: Philip Alexander, MD College Station, Texas, US [email protected] 07 3 2023 2023 19 2 107108 08 2 2023 08 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Philip Alexander, MD, is a native Texan, retired physician, and accomplished musician and artist. After 41 years as an internal medicine physician, Dr. Phil retired from his practice in College Station in 2016. A lifelong musician and former music professor, he often performs as an oboe soloist for the Brazos Valley Symphony Orchestra. He began exploring visual art in 1980, evolving from pencil sketches--including an official White House portrait of President Ronald Reagan--to the computer-generated drawings featured in this journal. His images, which first appeared in this journal in the spring of 2012, are his own original creations. If you would like to see your art published in the Methodist DeBakey Cardiovascular Journal, submit your creation online at journal.houstonmethodist.org as a "Humanities" entry. pmcImage 1 Sisters. Sisters Image 2 What Happy Looks Like! What Happy Looks Like! |
PMC10000322 | Ann Glob Health Ann Glob Health 2214-9996 Annals of Global Health 2214-9996 Ubiquity Press 10.5334/aogh.3871 VoR Original Research Surgical Capacity in Public and Private Health Facilities After a Five-Year Strategic Plan Implementation in Ethiopia: A Cross Sectional Study Merga Kassa Haile MD [email protected] 1 Gebreegziabher Senedu Bekele PhD 1 Getachew Edlawit Mesfine MD 1 Sibhatu Manual Kassaye MD 2 Beshir Hassen Mohammed MD 3 Kumssa Tsegaye Hailu MSc 1 Ashuro Akililu Alemu PhD 1 Alemayue Endawoke Amsalu PhD 1 Teferi Mikiyas MD 3 Taye Desalegn Bekele MD 3 Meshesha Berhane Redae MD 2 Zewude Wuletaw Chane MD 4 Shagre Mulatu Biru PhD 15 1 Armauer Hansen Research Institute, Ethiopia 2 Jhpiego Ethiopia, Johns Hopkins University Affiliate, Ethiopia 3 Ministry of Health (MoH), Ethiopia 4 St. Paul's Hospital Millennium Medical College, Ethiopia 5 Department of Health Sciences, Child and Family Health, Lund University, Lund, Sweden CORRESPONDING AUTHOR: Kassa Haile Merga, MD Armauer Hansen Research Institute, Ethiopia [email protected] 09 3 2023 2023 89 1 1805 6 2022 16 1 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Background: Surgical capacity is critical for ensuring optimum access to safe, affordable, and timely emergency and essential surgical care (EESC) in middle-income countries (LMICs) like Ethiopia. A five-year strategic plan has been implemented during 2016-2020 in Ethiopia to improve surgical capacity. Objectives: This study aims to evaluate the impact of the five-year strategy in surgical capacity in the country. Methods A cross sectional survey was conducted in 172 health care facilities in Ethiopia from December 30, 2020, to June 10, 2021. Descriptive statistical analysis was done using STATA statistical software Version 15. Findings: A total of 2,312 surgical workforces were available and, the surgical workforce to population ratio ranged from 1.13:100,000 for public specialized hospitals to 10.8:100,000 for health centre operation room (OR) blocks. Surgical bed to population ratio was 0.03:1000 population, and the average numbers of OR tables per facility were 34. Nearly 25% and 10% of OR tables were not functional in public primary hospitals and private hospitals, respectively. The average surgical volume to population ratio was 189:100,000. Conclusions Following the implementation of surgical care strategy, the surgical workforce density has increased. However, the study revealed that there is still a huge unmet gap in surgical capacity. The improvement in surgical volume is very low compared to the increment in the surgical workforce density. In addition to the investment being made to build surgical capacity, emphasis needs to be put on surgical system design and strengthening surgical system efficiency. surgical care surgical capacity safe surgery health facility cross-sectional Ethiopia Ministry of Health, Ethiopia Ministry of Health, Ethiopia. pmcIntroduction Lack of access to safe, affordable and timely emergency and essential surgical care (EESC) is a major gap to ensure universal health coverage (UHC) in middle-income countries (LMICs). Consequently, this problem poses to an increased mortality, morbidity and avoidable disability and deformity . In order to avert these problems in LMICs and improve their capability to deliver EESC, enhancing the capacity of health facilities with surgical workforce, infrastructure, medications, equipment and supplies is crucial . According to the Lancet Commission on Global Surgery (LCoGS), capacity, in terms of workforce and infrastructure is one of the four components to improve access to surgery. LCoGS sets targets to be achieved by 2030. Of these, the main ones are 80% coverage of essential surgical and anaesthesia services per country (within two hours access to the facility), at least 20 surgical workforce per 100,000 population, 5,000 procedures per 100,000 population annually, and 100% protection against catastrophic expenditure from out-of-pocket payments for surgical and anaesthesia care . However, many LMICs have challenges to achieve these targets . The Save Lives through Safe Surgery strategic plan (SaLTs) was implemented in Ethiopia for five-years, 2016-2020, intended to address the huge unmet need for basic surgical care services. The proposed strategies were well aligned with the Health Sector Transformation Plan 2 (HSTP2), recommendations of the World Health Organization (WHO) and quality strategy. This strategy was instrumental to define and standardize the minimum care packages needed to expand EESC. The SaLTS strategy had eight strategic pillars, three of which were focused on surgical capacity (infrastructure, supplies and logistics management, and human resource development) . Before and at the beginning of the strategic period there was a critical gap in the health workforce in general and the surgical workforce in particular . The surgery, anaesthesia, and obstetrics workforce (SAO) density was 0.35:100,000 population and the surgical volume was 43:100,000 population . As to our knowledge, there is limited evidence which showed the surgical capacity of the Ethiopia comparing with the recommendations of WHO and the LCoGS. Therefore, the aim of this study was to assess the surgical capacity and its effect on surgical volume in different levels of health care strata in Ethiopia after the implementation of a five-year strategic plan. Methods Study design Health facility based cross-sectional study with retrospective data review was conducted from December 30, 2020 to June 10, 2021 to assess the surgical capacity and its effect in surgical volume after implementing the five-year SaLTS I strategy in Ethiopia. Study setting Ethiopia is the second most populous country of Africa and ranks 12th in the world with a population of about 101 million in 2020 . Primary Health care units (PHCUs (17,550 health posts and 3,735 health centres) are the main sites of primary health care services, especially for rural communities in Ethiopia. Hospital-based services are provided by 353 hospitals that are categorized into primary, general and specialized hospitals. A total of 282 government health facilities and 45 private hospitals were providing surgical care in the country during the study period. This program evaluation was conducted in 172 sample public and private health facilities. Ministry of Health of Ethiopia implemented a five-year surgical care plan to improve access to safe and affordable emergency and essential surgical care. Sampling procedure and sample size A multi-stage stratified random sampling method was used to select study sites (public and private health care facilities). Two hundred eighty two government hospitals were providing emergency and essential surgical care in Ethiopia. Of these 26 were referral hospitals, 75 were general hospitals and 181 were primary hospitals. The required sample size for the study was estimated using a single population proportion formula for a finite population with 5% margin of error and 95% level of confidence (P = 0.5). The sample size was determined to be 163 public hospitals and with stratification, 105 primary hospitals, 43 general hospitals, and 15 referral hospitals were included. Among the 45 private health facilities providing surgical care in Ethiopia, 40 of them were sampled. This makes 203 total study sites. We randomly selected the health facilities from each stratum. However, because of security issues in Ethiopia we could not access all health facilities that were selected randomly, and we decided to replace some health facilities which were convenient assuming that hospitals in the same strata are homogeneous. Accordingly, a total of 172 study sites take part in the study. Data collection procedures and tools We used Surgical Assessment Tool (SAT), jointly developed by the Harvard Program in Global Surgery and Social Change (PGSSC) and the WHO. The tool was adopted and validated in the context of Ethiopian health facilities . The assessment consisted of hospital visit and interviews with hospital directors and surgical and anaesthesia care providers using the tool designed to assess the domains of - infrastructure, workforce (focused on specialist surgical, obstetrics, and anaesthetics care providers), Medicine, equipment, and supplies. Data collectors received adequate training about the entire process of data collection including quality control measures (such as completeness, correctness, concordance), piloted and synchronizing, and archiving the data with Research Electronic Data Capture (REDCap). Data collection was focused mainly on the number of surgical workforce by profession (Surgeon, Anaesthetist, Obstetrician, Integrated Emergency Surgical Officers (IESO), and Nurse Anaesthetists) at primary, general and specialized Hospitals, Infrastructure, including surgical beds and operation rooms (ORs), tables, intensive care units (ICUs), medical equipment and supplies, and surgical volume. The collected data were uploaded to the REDCap. Data management and analysis Data cleaned, entered, and then exported into STATA statistical software Version 15 for further statistical analysis. Additional data cleaning and consistency checks were done to detect outliers and inconsistent variables. Descriptive statistics: Percentage, frequency, and visual graphs were used. Ethical consideration Ethical clearance was obtained from the Armauer Hansen Research Institute (AHRI) ethical review committee. Letter of support to conduct the evaluation was obtained from the Ministry of health (MOH)-Ethiopia. Additionally, letters of support and permissions were obtained from the local health offices authorities to conduct data review at the selected health facilities. Role of the funding source This study was funded by the MOH-Ethiopia. Jhpiego Ethiopia gave additional support to complete the data collection and write up workshop. Experts from MOH-Ethiopia, AHRI and Jhpiego Ethiopia lead the design and implementation of the project. Results Health facilities This study included a total of 172 health facilities (81.4% public health facilities and 18.6% private health facilities). Of the public health facilities 44.8% and 22.1% were primary and general hospitals, respectively (Table 1). Table 1 Level and number of evaluated health care facilities from December 30, 2020 to June 10, 2021, Ethiopia. HEALTH CARE FACILITY LEVEL NUMBER PERCENTAGE Public Specialized Hospitals 16 9.30 Public General Hospitals 38 22.09 Public Primary Hospitals 77 44.76 Health Centre OR Blocks 9 5.23 Private Hospital 32 18.60 Total 172 100 Surgical workforce Health facilities had a total of 2,312 surgical workforce. Of those, 51.14% and 22.98% of Surgeons (General, neurosurgeons and orthopaedic surgeons), 48.27% and 11.67% of anaesthesia care providers (anaesthesiologists or anaesthetists) and 49.4% and 23.5% of obstetricians were working at public specialized hospitals and private hospitals, respectively. Fifty-nine percent and 30.2% of Integrated Emergency Surgical Officers (IESO) were available in public primary and general hospitals, respectively (Table 2). Table 2 Number of surgical workforce available in the evaluated health care facilities from December 30, 2020 to June 10, 2021, disaggregated by level of health care, Ethiopia. HOSPITAL STAFF NUMBER OF AVAILABLE HUMAN RESOURCE SPECIALIZED HOSPITAL N = 16 GENERALIZED HOSPITAL N = 38 PRIMARY HOSPITAL N = 77 HEALTH CENTRE OR BLOCK N = 9 PRIVATE HOSPITAL N = 32 TOTAL Surgeons (General, neurosurgeons and orthopaedic surgeons) 336 (51.14%) 123 (10.72%) 47 (7.15%) 0.00% 151 (22.98%) 657 (100%) Anaesthesiologists or anaesthesia care providers 364 (48.27%) 157 (20.82%) 126 (16.71%) 19 (2.52%) 88 (11.67%) 754 (100%) Obstetrician 165 (49.40%) 76 (22.75%) 16(4.79%) 0.00% 77 (23.05%) 334 (100%) IESO 10 (3.02%) 100 (30.21%) 194 (58.61%) 18 (5.44%) 9 (2.72%) 331 (100%) Nurse anaesthetists 14 (5.93%) 94 (39.83%) 79 (33.47%) 2 (0.85%) 47 (19.92%) 236 (100%) Total surgical work force 889 (38.45%) 550 (23.79%) 462 (19.98%) 39 (1.69%) 372 (16.09%) 2312 (100%) Surgical work force to population ratio The ratio of the surgical workforce to population served ranges from 1.31:100,000 population for public specialized hospital to 10.8:100,000 population for the health center OR blocks (Table 3). Table 3 Ratio of surgical workforce per 100,000 populations served from December 30, 2020 to June 10, 2021, disaggregated by level of care, Ethiopia. HEALTH CARE FACILITY LEVEL NUMBER OF EVALUATED HEALTH FACILITIES CATCHMENT POPULATION TO BE SERVED *NUMBER OF SURGICAL WORKFORCES SURGICAL WORKFORCE RATIO PER 100,000 POPULATION SERVED *Health centre OR block 9 360,000 39 10.8:100,000 population Public primary hospital 77 6,160,000 462 7.5:100,000 population Public general hospital 38 47,500,000 550 1.2:100,000 population Public specialized hospital 16 68,000,000 889 1.3:100,000 population Note: Private hospitals do not have specific cathment population. Surgical beds The total numbers of hospital beds available in the included hospitals were 18,418, 21% of which were surgical and 18% obstetrics care hospital beds. In the 172 health facilities, there were 232 and 398 functional operation rooms for minor and major surgeries, respectively. Specialized hospitals had 1,375 surgical beds (trauma, general surgery and orthopaedics) and 1,089 obstetric/gynaecologic beds. Public generalized hospitals had 1,139 surgical beds and 937 gynaecologic/obstetric beds. Private hospitals had 674 surgical beds and 380 gynaecologic/obstetric beds. On the other hand, 99 of functioning operating rooms for major surgical procedures were illustrated in public primary hospitals while private hospitals and public specialized hospitals had 89 and 90 functioning major operating rooms (Table 4). Table 4 Number of available surgical beds from December 30, 2020 to June 10, 2021, disaggregated by health care facility level, Ethiopia. HOSPITAL BEDS NUMBER OF AVAILABLE SURGICAL BEDS BY HEALTH CARE FACILITY LEVEL SPECIALIZED HOSPITAL GENERALIZED HOSPITAL PRIMARY HOSPITAL HEALTH CENTRE OR BLOCK PRIVATE HOSPITAL TOTAL 7,330 4,864 3,699 159 2,366 18,418 Surgical beds (Trauma, General Surgery and Orthopaedics) 1,375 1139 726 36 674 3,950 Obstetric and gynaecologic beds 1,089 937 843 116 380 3,365 Functioning operating rooms (Minor surgery) 71 42 77 8 34 232 Functioning operating rooms (Major surgery) 110 90 99 10 89 398 Ratio of surgical beds to the population served The total number of surgical beds in the included health facilities ranges from 36 in health centres OR blocks to 1,375 in specialized hospitals. The ratio of surgical beds to the population served is: 1:10,000, in Health Centre OR block, 1:8484, in Public Primary Hospital, 1:41703, in Public General Hospital, and 1:49454 in Public Specialized Hospital (Table 5). Table 5 Ratio of surgical beds to total population served disaggregated by level of health care, Ethiopia, December 30, 2020 to June 10, 2021. HEALTH CARE FACILITY LEVEL CATCHMENT POPULATION NUMBER OF EVALUATED HEALTH CARE FACILITIES TOTAL NUMBER OF SURGICAL BEDS SURGICAL BEDS TO POPULATION RATIO Public Primary Hospital 6,160,000 77 726 1:8484 Public General Hospital 47,500,000 38 1139 1:41703 Public Specialized Hospital 68,000,000 16 1375 1:49454 Health Centre OR block 360,000 9 36 1:10,000 Note: Private hospitals do not have specific cathment population. Operating room (OR) tables functionality The average numbers of operating tables (OTs) in primary hospitals were 2.26 and 75.28% were functional. The average numbers of OTs in private hospitals were 3.6 and 89.65% were functional. The average numbers of OTs in the general and specialized hospitals were 3.28 and 9.9, and of these 90.4% and 84.8% were functional, respectively (Table 6). Table 6 Proportion of functional operating theatre tables in a 90 days interval of the study period starting from September 2020 to May 2021, disaggregated by level of health care, Ethiopia. HEALTH CARE FACILITY LEVEL NUMBER OF HEALTH FACILITIES EVALUATED TOTAL NUMBER OF FUNCTIONAL ORS TOTAL NUMBER OF OT TABLES NUMBER OF FUNCTIONING OT TABLES PROPORTION OF FUNCTIONING OT TABLES AVERAGE NUMBER OF OT TABLES PER FACILITY Public Primary Hospital 77 176 174 131 75.28% 2.26 Public General Hospital 38 132 125 113 90.40% 3.28 Public Specialized Hospital 16 181 158 134 84.81% 9.87 Health Centre OR block 9 18 15 12 80.00% 1.66 Private Hospitals 32 123 116 104 89.65% 3.63 Total 172 630 588 494 84.01% 3.42 Reasons for operating room tables not in use The reasons for non-utilised OR tables ranged from non-functional OR tables (34.5%) to repurposing the OR table for COVID-19 treatment (3.63%), and lack of skilled professionals (3.63%). Twenty-one point eight percent of the OR tables are not functional due to the elective surgical service is not yet started in the facilities . Figure 1 Reasons for operating room tables not in use in public primary, public general hospitals and public specialized hospitals in a 90 days interval of the study period starting from September 2020 to May 2021, Ethiopia. Figure 1 Reasons for operating room tables not in use in public primary, public general hospitals and public specialized hospitals in a 90 days interval of the study period starting from September 2020 to May 2021, Ethiopia Availability of Medical Equipment and supplies Seventy-seven primary hospitals were assessed and 24% and 49.6% did not have adult and paediatric McGill forceps, respectively. About 35.1%, 27.3% and 24.7% of primary hospitals had no tracheostomy set, chest tube insertion instrument, and splints for arm and legs, respectively. Nearly 12% of primary hospitals did not have electrocautery and there was shortage in 66.7% of health centre OR blocks. Similarly, the facilities reported that from 64.5% to 30.6% had a shortage in electrocautery (Table 7). Table 7 Availability of emergency and essential Major and minor surgical care kits, OR equipment and supplies, reporting period starting from September 2020 to May 2021, disaggregated by level of health care facilities. EMERGENCY AND ESSENTIAL SURGICAL CARE EQUIPMENT AND SUPPLIES LEVEL OF HEALTH CARE FACILITY PRIMARY HOSPITALS (N = 77) GENERAL HOSPITALS (N = 38) SPECIALIZED HOSPITALS (N = 16) HEALTH CENTRE OR BLOCKS (N = 9) PRIVATE HOSPITALS (N = 32) ABSENT N (%) AVAILABLE WITH SHORTAGE N (%) FULLY AVAILABLE N (%) ABSENT N (%) AVAILABLE WITH SHORTAGE N (%) FULLY AVAILABLE N (%) ABSENT N (%) AVAILABLE WITH SHORTAGE N (%) FULLY AVAILABLE N (%) ABSENT N (%) AVAILABLE WITH SHORTAGE N (%) FULLY AVAILABLE N (%) ABSENT N (%) AVAILABLE WITH SHORTAGE N (%) FULLY AVAILABLE N (%) Scalpel with blades 1(1.30%) 17(22.08%) 59(76.62%) 0 2(5.41%) 35(94.59%) 1(6.25%) 1(6.25%) 14(87.50%) 0 2(22.22%) 7(77.78%) 0 1(3.23%) 30(96.77%) Retractors 0 15(19.48%) 62(80.52%) 0 1(2.7%) 36(97.3%) 0 1(6.25%) 15(93.75%) 0 0 9(100%) 0 1(3.23%) 30(96.77%) Scissors 0 18(23.38%) 59(76.62%) 0 7(18.92%) 30(81.08%) 1(6.25%) 3(18.75%) 12(75%) 0 1(11.11%) 8(88.89%) 0 1(3.23%) 30(96.77%) Tissue forceps 0 16(20.78%) 61(79.22%) 0 7(18.92%) 30(81.08%) 1(6.25%) 2(12.50%) 13(81.25%) 0 1(11.11%) 8(88.89%) 0 1(3.23%) 30(96.77%) Needle holder 0 19(24.68%) 58(75.32%) 0 6(16.22%) 31(83.78%) 1(6.25%) 2(12.50%) 13(81.25%) 0 0 9(100%) 0 1(3.23%) 30(96.77%) Adult McGill forceps 24(32%) 17(22.67%) 34(45.33%) 2(5.41%) 5(13.51%) 30(81.08%) 0 4(26.67%) 11(73.33%) 5(55.56%) 2(22.22%) 2(22.22%) 1(3.23%) Paediatric McGill forceps 38(49.35%) 15(19.48%) 24(31.17%) 13(36.11%) 4(11.11%) 19(52.78%) 1(6.67%) 5(33.33%) 9(60%) 8(88.89%) 1(11.11%) 0 4(12.90%) Needles & sutures 0 20(25.97%) 57(74.03%) 0 7(18.92%) 30(81.08%) 1(6.25%) 2(12.50%) 13(81.25%) 0 1(11.11%) 8(88.89%) 0 3(9.68%) 28(90.32%) Suction pump 1(1.3%) 30(38.96%) 46(59.74%) 0 11(28.95%) 27(71.05%) 1(6.25%) 5(31.25%) 10(62.50%) 0 1(11.11%) 8(88.89%) 0 Light source (lamp & flash light) 3(3.90%) 38(49.35%) 36(46.75%) 1(2.70%) 14(37.84%) 22(59.46%) 1(6.25%) 6(37.50%) 9(56.25%) 0 2(22.22%) 7(77.78%) 0 2(6.45%) 29(93.55%) Tourniquet 15(19.48%) 23(29.87%) 39(50.65%) 3(8.11%) 6(16.22%) 28(75.68%) 3(18.75%) 5(31.25%) 8(50%) 2(2.22%) 2(2.22%) 5(5.56%) 0 3(9.68%) 28(90.32%) Splints for arm, leg 19(24.68%) 23(29.87%) 35(45.45%) 12(32.43%) 3(8.11%) 22(59.46%) 3(18.75%) 5(31.25%) 8(50%) 5(55.56%) 3(33.33%) 1(11.11%) 2(6.45%) 2(6.45%) 27(87.10%) Electrocautery 9(11.69%) 22(28.57%) 46(59.74%) 0 11(30.56%) 25(69.44%) 0 8(50%) 8(50%) 6(66.67%) 2(22.22%) 1(11.11%) 0 2(6.45%) 29(93.55%) Chest tubes insertion equipment 21(27.27%) 28(36.36%) 28(36.36%) 5(13.51%) 8(21.62%) 24(64.86%) 3(18.75%) 3(18.75%) 10(62.50%) 9(100%) 0 0 2(6.45%) 1(3.23%) 28(90.32%) Tracheostomy set 27(35.06%) 20(25.97%) 30(38.96%) 8(21.62%) 8(21.62%) 21(56.76%) 1(6.25%) 2(12.50%) 13(81.25%) 9(100%) 0 0 0 2(6.45%) 29(93.55%) Surgical Volume The total number of surgeries in the three months of study period was 57,722. When this figure is calculated to give the annual volume of surgery, it is around 230,886 surgeries annually. This makes the average surgical volume to be 189 per 100,000 population in Ethiopia. Discussion We included 172 health facilities from the primary, secondary, and tertiary levels of care, from both the public and private sectors. The study was done to evaluate a five years strategic plan which was implemented to improve surgical care. The availability of specialist surgeons, gynaecologists, and anaesthesiologist decreases when we go through from the higher to the lower level of health care in Ethiopia, and the reverse is for IESO. This might be one of the reasons for patient referrals to specialized care, and in line with the government investment. Similarly, the lower health care facilities have limited infrastructure: surgical beds, equipment, and supplies compared to the higher level of care for the same reason. The private health facilities are well staffed with surgeons and obstetricians next to the public specialized hospitals, whereas health centre OR blocks are exclusively equipped with IESO and Anaesthesia providers. The surgical workforce ratio per 100,000 populations is very low compared to the target sated by the LCoGS, but it is 10.8:100,000 populations which is substantially higher for health centre OR blocks than primary and general hospitals. This might be due to the fact that health centre OR blocks were established only in urban settings with the expectation to serve one health centre OR block for 40,000 catchment area population (HSTP 2), which gives an advantage of serving less catchment area population when compared to the health facilities that exist outside of the urban setting. However, the Lancet Commission target for 2030 is 20 per 100,000 population, which shows that the current Ethiopian status is far behind the target . This finding is in line with cross-sectional studies conducted previously in Ethiopia and Liberia . Therefore, interventions including strengthening of the existing task shifting approach and monitoring of its effectiveness are among the viable ways to scale up the surgical workforce. Nevertheless, the specialized heath workforce capacity was high in the higher health care facilities (7% vs 51%) in primary and tertiary hospitals which is much higher than the finding in the study in rural India (13.8% vs 4.7%), respectively . The average numbers of hospital beds available at all levels were in the range of the Ethiopian standard. Surgical, gynaecology, and obstetrics beds account for 40% of the total hospital beds. The other finding is that several OR tables are non-functional, 25% of them in primary hospitals while about 10% in private hospitals. Similarly, several operation rooms are not in use and the main reason was non-functional OR table followed by lack of elective surgery service. The availability of surgical beds is 0.03 surgical beds:1000 people; this is markedly lower than the total number of 0.3 hospital beds:1000 population ratio in Ethiopia in 2016 . In contrast, the availability of surgical beds reported in this study is also lower than that in a study conducted in South Africa . Possible reason include the Gross Domestic Product (GDP) of the South Africa is better than our study setting, which might have attributed for availability of medical equipment. In this study, the average number of operation tables per facility was 3.4, which is very low to achieve the Lancet Commission target of 5000 procedures per 100,000 populations. In this study, health care facilities are lacking a variety of surgical items which is creating a barrier to the ability of the health system to deliver health services to patients. The shortage of the medical equipment is higher in primary hospitals than specialized hospitals. The possible reason might be poor maintenance and repairs as well as limited financial resources are responsible for the shortages. Therefore, proper management is required to develop and implement procurement, maintenance and quality control plans. This study revealed that the surgical capacity in Ethiopia is far behind from the targets of the LCoGs. However, the surgical workforce has increased by nearly fourteen-fold than it has been four years before (from 0.35 to 5.19:100,000 population). This may be due to the accelerated training of surgical workforce in Ethiopia including IESO and nurse anaesthetists . The health care facilities that can provide EESC have also increased. All this is intended to enhance access for surgical and increase annual surgical volume. Regardless, even with this progressive increment of capacity for surgical care, the surgical volume didn't show improvement that can match with the growth in capacity (Annual estimated volume increased from around 200,000 to 347,976 after five years or 43:100,000 to 261.5:100,000 population) . This might be due to deficiency in system design and management intending to improve efficiency in surgical care. As like any cross-sectional studies, this study also has a number of limitations. Firstly, due to the security situation we were not able to include all the health facilities selected for the study, although we did replacement for some health facilities. This may put nationwide representation of the study under the question. Moreover, as this study was conducted in the era of the COVID-19 pandemic, it might have affected the activities of health care facilities. Nevertheless, this study is believed to provide a crucial insight about surgical capacity and related challenges at different levels of health care delivery in Ethiopia, thus, the result could be used as a base to develop surgical capacity improvement strategies. Conclusions and recommendations Overall, this surgical capacity assessment revealed critical gaps in all parameters included in the assessment. However, there is an increment of health care facilities and the surgical workforce in the past five years that can provide essential and emergency surgical care. Nevertheless, surgical volume did not match with the capacity improvement for surgical care. This implies, there is a need to give due emphasis in system design and management to improve efficiency and effectiveness in surgical care parallel to capacity building. The findings from this assessment can be used as a crucial input for the development of the country's strategic plan of Safe Surgery intervention and can guide interventions to strengthen the surgical system in Ethiopia and other similar settings with resource constraints. Funding Information Ministry of Health, Ethiopia. Competing Interests The authors have no competing interests to declare. Author Contributions All authors had access to the data and a role in writing the manuscript. 1 WHO. Surgical Care Systems Strengthening. 2017; 1-45. 2 Spiegel DA, Price RR. Essential Surgical Care: 2011 and Beyond. World J Surg. 2013; 37 (7 ): 1462-9. DOI: 10.1007/s00268-012-1831-6 23150072 3 Kouo-Ngamby M, Dissak-Delon FN, Feldhaus I, Juillard C, Stevens KA, Ekeke-Monono M. A cross-sectional survey of emergency and essential surgical care capacity among hospitals with high trauma burden in a Central African country. BMC Health Serv Res. 2015; 15 (1 ). DOI: 10.1186/s12913-015-1147-y 4 Meara JG, Greenberg SLM. The Lancet Commission on global surgery global surgery 2030: Evidence and solutions for achieving health, welfare and economic development. Surg. 2015; 157 (5 ): 834-5. DOI: 10.1016/j.surg.2015.02.009 5 Carlson LC, Lin JA, Ameh EA, et al. Moving from data collection to application: A systematic literature review of surgical capacity assessments and their applications. World J Surg. 2015; 39 (4 ): 813-21. DOI: 10.1007/s00268-014-2938-8 25566980 6 Meara JG, Leather AJM, Hagander L, et al. Global Surgery 2030: Evidence and solutions for achieving health, welfare, and economic development. Lancet. 2015; 386 (9993 ): 569-624. DOI: 10.1016/S0140-6736(15)60160-X 25924834 7 Weiser TG. Surgical capacity indicators in 2018 and beyond. Updat Anaesth. 2018; 33 : 9-10. 8 Odinkemelu DS, Sonah AK, Nsereko ET, et al. An Assessment of Anesthesia Capacity in Liberia: Opportunities for Rebuilding Post-Ebola. Anesth Analg. 2021; 132 (6 ): 1727-37. DOI: 10.1213/ANE.0000000000005456 33844659 9 Bhatia MB, Mohan SC, Blair KJ, et al. Surgical and trauma capacity assessment in Rural Haryana, India. Ann Glob Heal. 2021; 87 (1 ): 1-11. DOI: 10.5334/aogh.3173 10 Federal Ministry of Health of Ethiopia. Ethiopia National Safe Surgery Strategic Plan 2016-2020; 2017. 11 Burssa D, Teshome A, Iverson K, et al. Safe Surgery for All: Early Lessons from Implementing a National Government-Driven Surgical Plan in Ethiopia. World J Surg. 2017; 41 (12 ): 3038-45. DOI: 10.1007/s00268-017-4271-5 29030677 12 Chao TE, Burdic M, Ganjawalla K, et al. Survey of surgery and anesthesia infrastructure in Ethiopia. World J Surg. 2012; 36 (11 ): 2545-53. DOI: 10.1007/s00268-012-1729-3 22851147 13 Federal Democratic Republic of Ethiopia Ministry of Health. Health Sector Transformation Plan II 2020/21-2024/25 (2013EFY-2017EFY). 2021; 25 (February ). 14 Hanna JS, Herrera-Almario GE, Pinilla-Roncancio M, et al. Use of the six core surgical indicators from the Lancet Commission on Global Surgery in Colombia: a situational analysis. Lancet Glob Heal. 2020; 8 (5 ): e699-710. DOI: 10.1016/S2214-109X(20)30090-5 15 Bank TW. |
PMC10000323 | J Belg Soc Radiol J Belg Soc Radiol 2514-8281 Journal of the Belgian Society of Radiology 2514-8281 Ubiquity Press 10.5334/jbsr.3012 VoR Case Report Giant Cell Tumor of Lumbar Vertebrae on MR and PET/CT: A Case Report and Literature Review Liu Xiangxiang 1 Lou Cen 1 Huang Zhongke [email protected] 1 1 Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, CN CORRESPONDING AUTHOR: Zhongke Huang Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, CN [email protected] 06 3 2023 2023 107 1 1712 11 2022 15 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Teaching Point: Giant cell tumor of bone may show a moderate to high FDG uptake, and attention should be paid to differentiate from malignant tumors. giant cell tumor vertebral tumors PET/CT MRI benign fibrous histiocytoma pmcIntroduction Giant cell tumor (GCT) is a common benign bone tumor, accounting for 5% of all primary bone tumors . Vertebral giant cell tumor is a very rare tumor, and imaging studies are challenging because it shares features with some other spinal lesions. There are not many reports on giant cell tumor of the lumbar spine, and even fewer reports on PET/CT of spinal GCT . Herein, we present a case of GCT of lumbar vertebrae on magnetic resonance imaging (MRI) and PET/CT, as well as review the literature. Case History A 45-year-old man with pain and numbness in the right lower limb for more than one year was referred for magnetic resonance imaging (MRI). MRI showed a large expansile lesion of the second lumbar vertebra . The right pedicle was involved, and part of the mass protruded into the spinal canal. The lesion was uniformly enhancing on contrast-enhanced MRI images . 18F-FDG PET/CT scan showed the expansile bone destruction of the second lumbar vertebra with increased FDG uptake (SUVmax: 11.8) . The cortex was eroded, with a residual bone crest. Figure 1 MRI. MRI Figure 2 PET/CT. PET/CT The patient underwent vertebral resection. Pathological diagnosis was a benign fibrous histiocytoma (BFH) (now considered GCT) . Light microscopy showed that spindle cells were arranged in a swirled structure . Osteoclast-type giant cells and foamy cells were scattered in the stroma. Figure 3 Pathological result. Pathological result Comments BFH shares common clinical symptoms, location, radiological characteristics, and histological features with GCT , causing difficulties in diagnosis. According to the latest WHO Classification of Tumors of Bone (2020), BFH of the spine is now classified as a heterogeneous GCT . GCTs are rare benign tumors, but with aggressive behavior. Spinal GCTs are even rarer, reported in less than 3% of cases . Despite benign in nature, GCTs generally exhibit high FDG uptake. A retrospective study of 20 patients from a single center showed that the SUVmax of spinal GCT ranged between 7.6 and 13.7, and the mean SUVmax was 10.4 +- 2.7 , consistent with our results (SUVmax: 11.8). Previous studies indicated that the high SUVmax of GCT was caused by overexpression of glucose transporter type 1 (GLUT-1) and hexokinase-2 in macrophages and giant cells, reactive fibroblast proliferation or enhanced angiogenesis . High FDG uptake may cause a misdiagnosis of malignancy. Conclusion GCT is a rare benign skeletal tumor. It shares features with some other malignant bone lesions on MRI and PET-CT and should be included in the differential diagnosis. Competing Interests The authors have no competing interests to declare. 1 Lin P, Lin N, Teng W, et al. Recurrence of giant cell tumor of the spine after resection: A report of 10 cases. Orthop Surg. 2018; 10 (2 ): 107-14. DOI: 10.1111/os.12375 29878714 2 Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR. Giant cell tumor of bone: Review, mimics, and new developments in treatment. Radiographics. 2013; 33 (1 ): 197-211. DOI: 10.1148/rg.331125089 23322837 3 Dejust S, Jallerat P, Soibinet-Oudot P, Jouannaud C, Morland D. Multimodality imaging features of a misleading sacral giant cell tumor in 18F-FDG PET/CT, bone scan, and MRI. Clin Nucl Med. 2020; 45 (10 ): 800-1. DOI: 10.1097/RLU.0000000000003148 32604109 4 Muheremu A, Ma Y, Huang Z, Shan H, Li Y, Niu X. Diagnosing giant cell tumor of the bone using positron emission tomography/computed tomography: A retrospective study of 20 patients from a single center. Oncol Lett. 2017; 14 (2 ): 1985-8. DOI: 10.3892/ol.2017.6379 28781642 5 Hoshi M, Takada J, Oebisu N, Hata K, Ieguchi M, Nakamura H. Overexpression of hexokinase-2 in giant cell tumor of bone is associated with false positive in bone tumor on FDG-PET/CT. Arch Orthop Trauma Surg. 2012; 132 (11 ): 1561-8. DOI: 10.1007/s00402-012-1588-2 22825642 6 McKinney AM, Reichert P, Short J, et al. Metachronous, multicentric giant cell tumor of the sphenoid bone with histologic, CT, MR imaging, and positron-emission tomography/CT correlation. AJNR Am J Neuroradiol. 2006; 27 (10 ): 2199-201.17110693 7 Ezgu MC, Cicek AF, Yasar S. Benign fibrous histiocytoma of the cervical vertebra: A rare case. Neurol India. 2019; 67 (1 ): 306-8.30860146 8 Mondal SK. Cytodiagnosis of benign fibrous histiocytoma of rib and diagnostic dilemma: A case report. Diagn Cytopathol. 2010; 38 (6 ): 457-60. DOI: 10.1002/dc.21245 20014125 9 Hattori T, Matsumine A, Uchida K, Nojima T, Sudo A. Benign fibrous histiocytoma of the talus: A case report. J Foot Ankle Surg. 2019; 58 (4 ): 762-5. DOI: 10.1053/j.jfas.2018.11.009 30962105 10 Ventura L, Petrella E, Piciucchi S, et al. Giant cell tumor of bone in an eighteenth-century Italian mummy. Virchows Arch. 2021; 479 (6 ): 1255-61. DOI: 10.1007/s00428-021-03192-5 34462806 11 Choi JH, Ro JY. The 2020 WHO classification of tumors of soft tissue: Selected changes and new entities. Adv Anat Pathol. 2021; 28 (1 ): 44-58. DOI: 10.1097/PAP.0000000000000284 32960834 12 Montgomery C, Couch C, Emory CL, Nicholas R. Giant cell tumor of bone: Review of current literature, evaluation, and treatment options. J Knee Surg. 2019; 32 (4 ): 331-6. DOI: 10.1055/s-0038-1675815 30449024 13 Park HL, Yoo IR, Lee Y, Park SY, Jung CK. Giant cell tumor of the rib: Two cases of F-18 FDG PET/CT findings. Nucl Med Mol Imaging. 2017; 51 (2 ): 182-5. DOI: 10.1007/s13139-016-0442-9 28559944 |
PMC10000325 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1178 VoR Review Open Treatments for Thoracoabdominal Aortic Aneurysm Repair Tanaka Akiko MD, PhD 1 Smith Holly N. MD, MBA 1 Safi Hazim J. MD 1 Estrera Anthony L. MD [email protected] 1 1 McGovern Medical School at UTHealth Houston, Houston, Texas, US CORRESPONDING AUTHOR: Anthony L. Estrera, MD McGovern Medical School at UTHealth Houston, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 4958 20 10 2022 22 11 2022 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Thoracoabdominal aortic aneurysms (TAAA) represent a unique pathology that is associated with considerable mortality if untreated. While the advent of endovascular technologies has introduced new modalities for consideration, the mainstay of TAAA treatment remains open surgical repair. However, the optimal conduct of open TAAA repair requires careful consideration of patient risk factors and a collaborative team effort to mitigate the risk of perioperative complications. In this chapter, we briefly outline the history of treating TAAA, preoperative preparation and postoperative care, and our operative techniques for treatment. thoracoabdominal aortic aneurysm TAAA open repair pmcHistory of Open Thoracoabdominal Aortic Aneurysm Repair Open repair of thoracoabdominal aortic aneurysm (TAAA) began in 1955 with Etheredge and colleagues,1 who were the first to report a successful TAAA open repair using a homograft, followed by DeBakey and colleagues a year later.2 The use of cardiopulmonary bypass or left heart bypass were not established at the time, and DeBakey and colleagues used a Dacron graft to shunt between the descending thoracic aorta and infrarenal abdominal aorta to minimize visceral and renal ischemia. By the 1970s, Crawford and colleagues established modern techniques to treat TAAA, which included three principles: (1) the inclusion technique to avoid damage to surrounding structures; (2) the reattachment of the renal and visceral arteries into the larger graft; and (3) the reattachment of the intercostal arteries to prevent paraplegia.3 The challenges in repairing TAAA are ischemic insults to multiple organs. In the 1960s, multiple approaches for spinal cord protection, as represented by cerebrospinal fluid (CSF) drainage, were introduced.4 The benefit of CSF drainage was confirmed by Hollier and colleagues in the late 1980s but fell into obscurity after Crawford and colleagues reported controversial outcomes in 1991.5,6 CSF drain was again proven to be beneficial for spinal cord protection in the 2000s.7 Before the 1990s, the "clamp-and-sew" technique was the primary surgical approach for treatment. The use of distal aortic perfusion (DAP)--or partial bypass--was first reported in 1956 by DeBakey and associates and revisited by Connolly and colleagues in 1971.2,8 The benefits of DAP include prevention of distal ischemia and reduction of cardiac afterload. It was also confirmed to reduce paraplegia in studies in the 1980s and 1990s.9,10 Use of DAP and CSF drainage combined with moderate passive hypothermia has reduced the overall spinal cord ischemia rate after extent I TAAA from 15% to less than 2%, and after extent II TAAA from 33% (50% with clamp time exceeding 40 minutes in the "clamp-and-go" era) to less than 4%.11 Although it remains difficult to unequivocally prove the benefit of intercostal reattachment, indirect evidence with improvement of motor evoked potential (MEP) and somatosensory evoked potential (SSEP) responses suggests spinal cord perfusion is improved with potential benefit. This contrasts with those who argue against this adjunct based on the collateral network concept of spinal cord circulation.12 Although disputed by some,12,13 patent intercostal arteries in the T8-T12 distribution should be reattached at the time of surgery to prevent immediate and delayed paraplegia.14 Patients with extent II and III are at risk for spinal cord ischemia, and reimplantation of T8-T12 should be considered regardless of neuromonitoring, if feasible. The concept of visceral perfusion with a shunt from the descending aorta to both renal arteries, the celiac axis, and the superior mesenteric artery was first described by Korompai and Hayward in 1975.15 Later, visceral and renal perfusion techniques using the roller pump became a standard technique to prevent organ ischemia.10 Preoperative Preparation Preoperative evaluation and preparation of the patient is crucial to optimize the postoperative outcomes after TAAA repair. Patients with severe chronic obstructive pulmonary disease, as suggested by a forced expiratory volume in 1 second of less than 0.8 L/min and a partial pressure of carbon dioxide greater than 45 mm Hg, should be evaluated by a pulmonologist and receive bronchodilators as well as pulmonary rehabilitation before repair. Preoperative renal function is a strong predictor of postoperative mortality after TAAA repair, and glomerular filtration rate is more sensitive than serum creatinine in predicting postoperative outcomes.16 Patients with a glomerular filtration rate less than 30 mL/min/1.73m2 have a mortality rate of more than 30%. Large aneurysms may cause "aortic dysphagia" as a result of intrinsic compression of the lower esophagus, leading to a nutritionally depleted state that may benefit from preoperative enteral alimentation. Classification for Descending Thoracic and Thoracoabdominal Aortic Aneurysm A classification for TAAA describes five anatomic extents: extent I extends from the left subclavian artery to just above the renal arteries; extent II from the left subclavian to the aortic bifurcation; extent III from the sixth intercostal space to the aortic bifurcation; extent IV from the 12th intercostal space to the aortic bifurcation; and extent V from the sixth intercostal space to just above the renal arteries . This classification has been used in the prediction of complications,17 especially the risk of spinal cord ischemia, which is highest for extent II TAAA. In our experience, significant disabling complications (composite of operative mortality, paraplegia/paraparesis, stroke, and dialysis) were more frequently seen in the order of extent II, extent III, extent I, extent V, and extent IV.17 Figure 1 Classifications of thoracoabdominal aortic aneurysms--the scheme of thoracoabdominal aortic aneurysms depicted by extent of aneurysm. Classifications of thoracoabdominal aortic aneurysms Operative Techniques for Open TAAA Repair Anesthesia and Monitoring After induction of general anesthesia, the patient is intubated with a double-lumen endotracheal tube. We place a large-bore, central, and venous catheter for rapid infusion along with a Swan-Ganz catheter for cardiac evaluation, and we monitor nasal and bladder temperatures for core temperature. Renal temperature is obtained later in the operative field using a needle-probe after exposing the retroperitoneal space. Electroencephalogram, somatosensory evoked potential (SSEP), and motor evoked potential (MEP) are also placed at this point. We then turn the patient to the right decubitus position to insert a CSF drainage catheter and advance 5 to 10 cm at the level of L3/L4, L4/L5, or L5/S1. We monitor the CSF pressure throughout the entire procedure and drain, as needed, to maintain the pressure below 10 mm Hg. Modification of anesthetic technique is required to not interfere with MEP and SSEP monitoring. Induction consists of narcotic loading: fentanyl citrate (10-15 mg/kg), midazolam (50 mg/kg), propofol (0.5 mg/kg), and cisatracurium (0.2 mg/kg). Patients are then maintained on a volatile agent (isoflurane) at 0.5 minimal alveolar concentration. Since 2019, induction has consisted of narcotic loading as follows: fentanyl citrate (2-5 mg/kg), midazolam (30-50 mg/kg), propofol (0.5-1 mg/kg), and rocuronium bromide (0.6-1mg/kg). Patients are then maintained on a volatile agent (sevoflurane) at 0.5 minimal alveolar concentration. We do not give any neuromuscular blockers during MEP monitoring. Cisatracurium 0.1 mg/kg may be given for closing the thoracoabdominal spaces or changing double lumen tracheal tube to single endotracheal tube at the conclusion of the surgery. SSEPs and MEPs are helpful to determine the conduct of operation, especially the timing of the intercostal artery reconstruction.18 An abnormal response is defined as a 10% change in latency or 50% change in amplitude from the baseline. Findings of abnormal SSEP or MEP warrant a series of corrective measures to improve spinal cord perfusion, including increasing the proximal mean blood pressure to at least 90 mm Hg and distal aortic pressure to at least 60 mm Hg. CSF pressure may be reduced by gravity drainage and hemoglobin increased by transfusion. Furthermore, additional patent intercostal arteries should be reimplanted, especially those between T8 and L1, as necessary. Positioning, Incision, and Exposure The patient should be positioned with the scapulars at a right angle to the edge of the operating table, stabilized by a bean bag, with both axillae well padded. The hips are tilted 60 degrees so that both femoral arteries are accessible . The left knee should be flexed and a pillow placed between both lower extremities. The patient is secured to the table with the bean bag vacuumed into a supportive shape. The table should then be flexed and the kidney rest elevated at the flexion point for greater lateral flexion and to improve access to the retroperitoneal space. Figure 2 Positioning and skin incision. Note the scapulars are at 90 degrees to the table but hips are rotated for abdominal and femoral exposures. Positioning and skin incision for open TAAA repair For most TAAA procedures, the incision begins at or below the level of the scapula, depending upon the proximal extent, which is then carried down to the costal cartilage along the anterolateral margin of the abdominal wall, lateral to the rectus sheath, to the level of the umbilicus or pubis as dictated by the distal extent of the aneurysm. The incision is extended below the umbilicus for extent II and III, or the incision can end above the umbilicus for extent I and V TAAA repairs. Access to the external iliac arteries may require extension of the incision to the pubis. The thoracic interspaces are defined by counting down from the first rib. The first rib is slightly difficult to palpate, but the second rib is easily found and confirmed as the posterior scalene muscle attaches to it. We routinely enter the sixth intercostal space for all extents. The chest is entered after the left lung is deflated, and the costal cartilage is cut anteriorly. The ribs above and below may be shingled or divided posteriorly if more proximal exposure is required in the thoracic cavity. The anterior muscular portion of the diaphragm is partially split, with special care to avoid injury to the phrenic nerve and reserve the pulmonary function .19 Figure 3 Diaphragm splitting. (1) Radial division, (2) lateral division, and (3) partial lateral division. Partial lateral division of the diaphragm with sparing of the phrenic nerve has been associated with enhanced postoperative recovery of diaphragmatic and pulmonary function. Note that we cut only one-third of the circumference. Diaphragm splitting The retroperitoneal space below the diaphragm should be dissected away from the diaphragm prior to the splitting. The left crus of the diaphragm and median arcuate ligament are divided to create an aortic hiatus for the graft.19 The retroperitoneal approach is preferred because it prevents the viscera (especially the small bowel) from obscuring the operative field, facilitates closure, and decreases water and heat loss. The left kidney and the viscera are mobilized medially, exposing the aorta from the aortic hiatus to the iliac bifurcation. A large ascending lumbar renal vein is encountered upon exposing the TAAA and must be ligated to avoid bleeding. The initial proximal clamp site just distal to the left subclavian artery can be safely secured with a circumferential blunt dissection using fingers along the lateral border of the trachea. Left Heart Bypass The left inferior pulmonary vein is used to drain the left heart bypass. On exposure of the left inferior pulmonary vein, the pericardium is opened posteriorly to the left phrenic nerve. Upon entering the pericardial cavity, small pericardial effusion is usually encountered. A pledgeted, 3-0 polypropylene purse-string suture is placed in the left inferior pulmonary vein, followed by a transverse incision. The venotomy is dilated, and the cannula is inserted into the left atrium and connected to the centrifugal pump and inline heat exchanger. Although the femoral artery can be directly cannulated using the Seldinger technique when large in caliber, it may be preferable to suture an 8-mm graft onto the femoral artery, as a sleeve for the cannula, to prevent ischemia to the leg. Myoglobinuria that occurs from warm ischemia to the leg with direct femoral artery occlusion for arterial cannulation may contribute to renal dysfunction after TAAA.20 Therefore, a sutured graft to the femoral artery may be used to prevent lower-leg ischemia during cannulation. As an alternative to avoid accessing the femoral artery, the distal aortic anastomosis can be performed initially using a premanufactured single-arm branched aortic graft (distal first technique). The sidearm of the tube graft is then connected to the inflow portion of the distal perfusion circuit. An advantage of using a left heart bypass is the ability to maintain proximal pressure above 100 mm Hg and distal pressure above 60 mm Hg. In addition, the presence of an inline heat exchanger allows the patient to be effectively warmed during the later stages of the procedure. Proximal Anastomosis The proximal clamp is placed either proximally or distally to the left subclavian artery, depending on the presence of atheromatous debris and aortic dissection. Sequential clamping of the distal aorta is used to minimize the ischemic insults to the viscera, kidneys, and spinal cord. Thus, the initial distal aortic clamp is placed at the level of T6, which is then moved distally to the distal descending thoracic aorta and to the infrarenal aorta. After placing the proximal and distal clamps, the proximal descending thoracic aorta is opened and all the thrombus is removed. In patients with chronic dissection, the initial lumen entered is usually a false lumen, and a flap between the false and true lumen must be excised. This step is important to visualize the hidden patent intercostal arteries in a small true lumen. The intercostal arteries within the initial opened segment are all ligated (ie, intercostal arteries above T6). The proximal aorta is circumferentially divided and lifted off the esophagus to prevent an inadvertent esophagograft fistula. Most frequently, 3-0 polypropylene is sufficient to perform proximal anastomosis. In cases with a fragile aortic wall, such as acute dissection and traumatic injury, 4-0 polypropylene is preferred. In patients with a calcified aorta, running 2-0 polypropylene may be used. The suture line begins at the posterior wall with an anchor technique. The posterior wall is selectively reinforced using a pledgeted suture of 3-0 or 4-0 polypropylene. A felt strip is usually avoided as it makes it difficult to search for the actual bleeding site after the anastomosis. Once that is completed, the anterior anastomosis is continued. This anastomosis is checked for hemostasis by releasing the clamp and occluding the graft. Any bleeding portions of the anastomosis are reinforced using interrupted pledgeted sutures. In cases of young patients, proximal aortic disease, or dissection in the aortic arch, the reversed elephant trunk technique is used to prepare for possible future proximal intervention. In cases of a previous stent graft, if it has type I endoleak, the graft should be removed and proximal/distal anastomosis should be performed to the native aorta. When the stent graft is well incorporated to the native aorta without signs of type I endoleak, the anastomosis can be performed by suturing the graft to the aortic wall and stent graft. The aorta should be transected at the level of anastomosis to allow for secure anastomosis. A 2-0 polypropylene suture is usually needed because the layers become thick and strong needles are required. Distal Anastomosis, Intercostal Artery Reattachment, and Visceral/Renal Artery Reconstruction The proximal clamp is now on the graft just distal to the anastomosis, and the distal clamp is moved to the end of the descending aorta. The remaining thoracic aorta is further opened. The patent T8-T12 intercostal arteries are preserved, but others are ligated upon opening the aorta. 3F balloon-tipped occlusion catheters can be used to temporarily occlude the T8-1T12 intercostal arteries to prevent steal phenomenon. The changes in MEPs and SSEPs will dictate when to reattach the T8-T12 intercostal arteries. There are three methods of intercostal reattachment: (1) loop reconstruction using a 14-mm Dacron graft connected to the main body Dacron graft in a side-to-end and side-to-side fashion to the intercostal artery of half loop for small number of pairs ; (2) side-to-side reconstruction by creating a side hole in the main Dacron tube graft and anastomosing to the intercostal arteries as an island; and (3) end-to-end reconstruction using an interposing 12-mm by 14-mm Dacron tube graft between the main Dacron graft and each pair of intercostal arteries. If signal changes are observed early during the clamp period, the important patent intercostal arteries within T8 through T12 are reattached immediately. We began using loop reconstruction as it seems to reduce the risk of graft thrombosis compared with direct end-to-end anastomosis from a side-arm graft. Otherwise, the reattachment can be performed with distal anastomosis and weaning off pump prior to protamine reversal. Figure 4 Intercostal artery reattachment techniques. (A) A 14-mm Dacron graft is anastomosed to the anterolateral surface of the main body graft as a loop to reconstruct the intercostal arteries in side-to-end fashion. (B) Similar to the loop graft but the proximal end may not be anastomosed back to the main body graft if reconstructing less than three pairs of intercostal arteries. The anastomosis to the intercostal arteries is performed in end-to-end fashion by beveling the 14-mm graft. (C) A side hole is made large enough to accommodate the intercostal arteries to be reattached and anastomosed as an island patch in side-to-side fashion. (D) A 12-mm x14-mm Dacron graft is used to reattach each pair of intercostal arteries in an end-to-end fashion. Intercostal artery reattachment techniques Then, the distal clamp is further moved below the infrarenal aorta and the visceral aorta is opened. The orifices of the celiac, superior mesenteric, and the left and right renal arteries are identified from the inside. Balloon-tip perfusion catheters are inserted into each orifice. The celiac axis and superior mesenteric artery are perfused with continuous blood while the renal arteries are infused with cold (4degC) crystalloid with potassium into the renal arteries until the left renal temperature reaches below 20degC (usually a total of 200-300 mL), which is supplemented by a bolus dose to maintain the temperature. Distal anastomosis is preferred prior to visceral and renal reconstruction to restore the pulsatile flow to the pelvis to improve spinal perfusion. In chronic type A or B dissection, the distal anastomosis is typically created in a fenestrated fashion (double barrel) without attempting to incorporate the flap or septum since it is difficult to discern the true from false lumen. The distal clamp is released to fill the graft with blood and evacuate the graft of all air and debris by placing the patient in the head-down position. The proximal clamp is slowly released to flush the graft in a prograde manner. The ostia of the visceral and renal vessels are examined and cleaned of atheromatous debris. If the ostia are less than 2 cm apart, then a single-island patch can be created or reattached to the side of the main graft with 3-0 polypropylene suture. If a vessel (most frequently the left renal artery) is separated from the other vessels, then a separate interposition bypass graft is performed using an 10-mm Dacron tube graft. In cases of Marfan syndrome or other connective tissue disorders in patients younger than 60 years of age, or with ostial separation of greater than 3 cm, a premanufactured side-branched thoracoabdominal aortic graft (STAG) is used with separate bypasses to each of the vessels . This is performed consecutively, starting with the celiac and superior mesenteric arteries and ending with the left renal artery. Creating buttons for each ostium facilitates suturing using running 4-0 polypropylene. Figure 5 Extent II thoracoabdominal aortic aneurysm repair with side-branched thoracoabdominal aortic graft (STAG). Extent II TAAA repair with STAG Once the patient is rewarmed to a nasopharyngeal temperature of 36degC and the bladder/rectal temperature is 35degC, DAP is discontinued. All cannulae are removed from the patient and sutures are secured. Heparinization is reversed using protamine sulfate after confirming good pulses in the cannulated femoral artery. Hemostasis and Closure Meticulous attention to hemostasis is mandatory and reduces coagulopathy. It is also important to interrogate the anastomoses. To prevent coagulopathy, hemostasis of muscle edges during thoracoabdominal incision should be managed prior to heparinization. All the mural thrombus in the aorta should be removed to search for intercostal arteries or small branches with patent orifice--and these should be ligated as they may later start to bleed. When cell salvage amount exceeds 30 to 40 units, appropriate blood products should be given to correct the coagulopathy.21 In cases of persistent coagulopathy, vacuum-assisted closure of the abdomen with sponge and pad packing may be instituted. Infusion of platelet-rich plasma may also be considered to reduce the intraoperative bleeding.22 Three No. 36 chest tubes are placed: one anteriorly; one posteriorly; and one right-angled above the diaphragm to prevent fluid accumulation in the phrenic sulcus. Before closure, intercostal nerve cryoanalgesia from T4 to T10 are performed to help control pain and minimize postoperative opioid use.23 After intercostal nerve cryoanalgesia is applied to T4 to T10 and chest tube placement, the diaphragm is reapproximated using a running No. 1 polypropylene suture. The intercostal space is closed using interrupted No. 2 braided absorbable (polyglactin 910) sutures. The lung is expanded, and the pericostal sutures are secured. A No.1 absorbable monofilament suture (polydioxanone) is used to close the muscular fascia of the chest, first reapproximating the serratus anterior muscle and then the latissimus dorsi muscle, followed by a layer of 2-0 or 3-0 braided absorbable sutures. The skin is closed subcuticularly with 4-0 polydioxanone sutures (or skin staples). The patient is placed in the supine position and the double-lumen tube is exchanged for a single-lumen tube. If there is swelling of vocal cord or coagulopathy requiring abdominal packing, the double lumen endotracheal tube is left in place. Postoperative Care All patients are cared for in an intensive care unit. Postoperative management is also important to avoid delayed paraplegia, and the goal systolic blood pressure should be set above 130 mm Hg by judicious use of blood and blood component therapy.24 CSF drainage is continued to maintain CSF pressure below 10 mm Hg. Delayed spinal cord injury (SCI) may occur after a period of normal motor function and remains a devastating complication.24 We keep the CSF drain until postoperative day 3 because our data demonstrated the peak incidence is in the second postoperative day.24 Once SCI occurs, the CSF drain status, oxygen delivery, and patient status (COPS) protocol should be instituted: The patient is placed flat and, if the spinal catheter is still in place, then drained freely without maximum amount for 7 days. The hemoglobin level is kept above 10 g/dL, and cardiac output is kept at an optimal level (cardiac index 2.5 L/min/m2). In more than 75% of cases, strength may be regained.25 MRI or CT imaging should be used to exclude epidural hematoma. Figure 6 When delayed paraplegia occurs, use a modified COPS protocol: Limitless Cerebrospinal fluid drainage to maintain pressure below 5 mm Hg; Oxygen delivery is optimized by keeping hemoglobin above 10 g/dL and cardiac index above 2.5 mL/min/body surface area m2; and optimize Patient Status by elevating the systolic blood pressure above 140 mm Hg. A modified COPS protocol for delayed paraplegia Summary The current standard practice of TAAA repair includes: perioperative CSF drainage; left heart bypass with mild hypothermia or cardiopulmonary bypass with moderate/deep hypothermia; sequential clamping; visceral and renal perfusion using roller pump; and aggressive reattachment of patent intercostal arteries within T8 - T12. Our group demonstrated that the use of DAP and CSF drainage, in combination with moderate passive hypothermia, has reduced the overall spinal cord ischemia rate after extent I TAAA from 15% to less than 2%, and after extent II TAAA from 33% (50% with clamp time exceeding 40 minutes in "clamp and go" era) to less than 4%.26 Key Points Repair of thoracoabdominal aortic aneurysm requires a coordinated team that includes anesthesia, perfusion, nursing, and surgeon. The adjuncts of distal aortic perfusion and cerebrospinal fluid drainage, as well as intercostal artery reattachment, are important for organ protection, including reducing paraplegia. Compartmentalizing the procedure, such as sequential clamping and paying attention to details, reduces bleeding and overall complications. Although we are in the era of endovascular surgery, open repair remains an important tool for addressing these complex conditions. Competing Interests Dr. Estrera is a consultant for WL Gore, CryoLife, Edwards Lifesciences, and Terumo Aortic. The other authors have no competing interests to declare. 1 Etheredge SN, Yee J, Smith JV, Schonberger S, Goldman MJ. Successful resection of a large aneurysm of the upper abdominal aorta and replacement with homograft. Surgery. 1955 Dec;38 (6 ):1071-81.13274266 2 DeBakey ME, Creech O Jr., Morris GC jr. Aneurysm of thoracoabdominal aorta involving the celiac, superior mesenteric, and renal arteries; report of four cases treated by resection and homograft replacement. Ann Surg. 1956 Oct;144 (4 ):549-73. doi: 10.1097/00000658-195610000-00004 13373247 3 Crawford ES. Thoraco-abdominal and abdominal aortic aneurysms involving renal, superior mesenteric, celiac arteries. Ann Surg. 1974 May;179 (5 ):763-72. doi: 10.1097/00000658-197405000-00032 4274686 4 Miyamoto K, Ueno A, Wada T, Kimoto S. 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Ann Thorac Surg. 2013 May;95 (5 ):1525-30. doi: 10.1016/j.athoracsur.2012.09.054 23245451 23 Tanaka A, Al-Rstum Z, Leonard SD, et al. Intraoperative Intercostal Nerve Cryoanalgesia Improves Pain Control After Descending and Thoracoabdominal Aortic Aneurysm Repairs. Ann Thorac Surg. 2020 Jan;109 (1 ):249-254. doi: 10.1016/j.athoracsur.2019.07.083 31521592 24 Sandhu HK, Evans JD, Tanaka A, et al. Fluctuations in Spinal Cord Perfusion Pressure: A Harbinger of Delayed Paraplegia After Thoracoabdominal Aortic Repair. Semin Thorac Cardiovasc Surg. 2017 Winter;29 (4 ):451-459. doi: 10.1053/j.semtcvs.2017.05.007 29698653 25 Estrera AL, Sheinbaum R, Miller CC 3rd, et al. Cerebrospinal fluid drainage during thoracic aortic repair: safety and current management. Ann Thorac Surg. 2009 Jul;88 (1 ):9-15; discussion 15. doi: 10.1016/j.athoracsur.2009.03.039 19559180 26 Safi HJ, Estrera AL, Azizzadeh A, Coogan S, Miller CC 3rd. 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PMC10000326 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1171 VoR Review Changing Management of Type B Aortic Dissections Eidt John F. MD [email protected] 12 Vasquez Javier MD 2 1 Texas A&M College of Medicine, Bryan, Texas, US 2 Baylor Scott and White Heart and Vascular Hospital, Dallas, Texas, US CORRESPONDING AUTHOR: John F. Eidt, MD Baylor Scott and White Heart and Vascular Hospital, Dallas, Texas, US [email protected] 07 3 2023 2023 19 2 5969 14 10 2022 12 1 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See The purpose of this manuscript is to review recent trends in the management of acute type B aortic dissection. Due to its efficacy and low morbidity, thoracic endografting has rapidly been adopted as the treatment of choice for most patients with malperfusion or rupture as a consequence of acute aortic dissection. This technology is increasingly applied to patients without rupture or malperfusion, so-called "uncomplicated" dissections, to reduce the incidence of late aneurysmal degeneration in the ungrafted segments of the thoracoabdominal aorta. A variety of techniques have been proposed, including intentional rupture of the dissection membrane to obliterate the false lumen as well as the candy-plug technique to eliminate retrograde flow in the false lumen. aortic dissection Knickerbocker Stablilise Instead stable thoracic endograft false lumen malperfusion pmcIntroduction Aortic dissection is the most common of the acute aortic syndromes. Despite contemporary advances in medical and surgical care, acute aortic dissection remains a highly lethal and morbid condition. It is estimated that up to a third of patients never reach the hospital.1 Of those surviving to reach definitive care, overall in-hospital mortality of type B aortic dissection (TBAD) approaches 15%.2 Recent epidemiological studies report a relatively stable incidence of acute aortic dissection between 3.5 and 6 per 100,000.3,4,5 Swedish researchers reported a significantly higher incidence of acute aortic dissection in men than women (9.1/100K vs 5.4/100K, P < .001).1 There appears to be an association with the increasing prevalence of hypertension in population-based studies.2 This article explores four significant trends in the management of type B aortic dissection: (1) adoption of a new classification system that resolves deficiencies of the DeBakey and Stanford systems; (2) recognition that thoracic endovascular aortic repair (TEVAR), the standard of care for treatment of complicated TBAD, fails to effectively prevent aneurysmal degeneration in the untreated aortic segments; (3) increasing use of TEVAR in uncomplicated TBAD despite the absence of definitive proof of efficacy; and (4) the emergence of a variety of techniques and devices designed to improve the long-term outcomes of TBAD. Anatomic Classification A number of classification schemes have been applied to aortic dissections, including the widely known DeBakey and Stanford systems. Both of these systems suffer from substantial deficiencies that led the Society for Vascular Surgery (SVS) and the Society of Thoracic Surgeons (STS) in 2020 to publish reporting standards that recommend the adoption of a new classification system based on the location of the primary entry tear and the longitudinal extent of the dissection.3 The aortoiliac arteries are divided into 11 zones beginning at the aortic valve and extending to the external iliac arteries . Type A aortic dissection (TAAD) describes a dissection in which the intimal tear is located in zone 0 of the ascending aorta. Figure 1 The thoracoabdominal aorta and the bifurcation are divided into 11 zones starting at the aortic valve and extending into the external iliac arteries. Acute dissections that involve the ascending aorta (zone 0) are designated type A. It is noteworthy that dissections involving zone 0 are predominantly intrapericardial, which can lead to the lethal triad of aortic insufficiency, pericardial tamponade, and coronary malperfusion. All dissections involving zones 1-11 are classified as type B (extrapericardial). 11 zones starting at the aortic valve and extending into the external iliac arteries In TBAD, the primary entry tear is in zones 1 through 11. The longitudinal extent of the dissection is designated with subscript zone numbers. Dissection includes the associated entities of intramural hematoma as well as partially or completely thrombosed false lumen. For example, a dissection with an entry tear in zone 3 and retrograde intramural hematoma encroaching on the left common carotid artery and extending into the left common iliac artery would be designated B2-10. A dissection with an entry tear in zone 0 extending to zone 4 would be designated A4 since the proximal extent is known to be zone 0. Finally, any dissection involving zone 0 but without an identifiable entry tear should be designated "I" for "indeterminate." The new system is based on recognition that dissections involving the intrapericardial portion of the aorta carry a lethal triumvirate of risks including aortic insufficiency, pericardial tamponade, and coronary malperfusion. As a result, surgery is typically recommended for all but the most moribund patients with TAAD because survival in the absence of surgical repair is uncommon. In contrast, medical management of uncomplicated TBAD has, until recently, been the standard of care. Time-Based Classification: Chronicity SVS/STS reporting standards recommend the following classification of aortic dissection based on the chronicity of dissection: (1) hyperacute < 24 hours; (2) acute 1 to 14 days; (3) subacute 15 to 90 days; and (4) chronic > 90 days. These categories were chosen because they reflect changes in the maturation of the dissection membrane that impact the response to treatment. In 1958, Hirst et al. reported that 21% of patients with acute or hyperacute (TAAD and TBAD) aortic dissection died within 24 hours, 80% died within 4 weeks, and 93% died within 1 year.6 Recently, the Starnes group at the University of Washington reported that all-cause mortality exclusively for TBAD was 15% at 1 year, 24% at 3 years, and 57% at 10 years.7 The cumulative incidence of aorta-related mortality was 8.9% at 1 year, 16.5% at 3 years, and 27.2% at 10 years and that of non-aorta-related mortality was 2.7%, 7.2%, and 29%, respectively.7 Acute Type B Dissection Classification of Acute TBAD (Complicated, Uncomplicated, and High-Risk) Acute TBAD most commonly presents with the sudden onset of back pain, although chest, abdomen, and extremity pain also are reported.2 The most serious consequences of acute aortic dissection are rupture and malperfusion. Most patients with frank rupture of TBAD never reach the hospital, or they arrive in extremis and expire before definitive treatment. Patients with contained rupture or signs of malperfusion are classified as "complicated" TBAD, and most require urgent surgical treatment to avoid excessive morbidity and/or mortality (Table 1).3 Table 1 Features of complicated, uncomplicated, and high-risk acute type B aortic dissection.3 UNCOMPLICATED COMPLICATED HIGH RISK True lumen diameter > 22 mm No high-risk features Malperfusion Total aortic diameter > 40 mm No malperfusion Rupture Radiographic malperfusion No rupture Refractory pain Hemothorax Refractory hypertension Readmission "Uncomplicated" TBAD dissections have no evidence of either frank or contained rupture and have no signs of end-organ malperfusion. Traditionally, these "uncomplicated" patients have been treated with optimal medical management, which entails "anti-impulse therapy" that employs strict blood pressure control as well as continuous monitoring for signs of end-organ ischemia or internal bleeding. Increasingly, these "uncomplicated" patients are treated with thoracic endovascular aortic repair (TEVAR) because of the recognition that the long-term success of medical management is suboptimal due to aneurysmal expansion of the false lumen. The STS/SVS identifies a third group of patients with TBAD who are at particularly high risk for the development of complications.3,4 Radiographic predictors of adverse aortic outcomes include total aortic diameter > 40 mm, false lumen > 22 mm, primary entry tear on the inner curve of the aortic arch (as opposed to the outer curve), and evidence of subclinical malperfusion such as asymmetrical renal perfusion on computed tomography angiography (CTA). Hemothorax based on characteristic imaging findings or confirmed with needle aspiration is a particularly worrisome finding. Other high-risk clinical features include refractory hypertension, persistent chest pain, and/or the need for hospital readmission typically due to recurrent pain and inadequate outpatient control of blood pressure. Management of Rupture in Complicated Acute TBAD There is little debate that emergency treatment of ruptured TBAD is appropriate in all but the most moribund patients. Patients should be taken immediately to a suitable procedure room with both endovascular and open surgical resources for resuscitation and treatment. Chest tubes should generally be discouraged prior to TEVAR for fear of inducing hemodynamic instability from sudden chest decompression. Permissive hypotension is recommended to avoid disruption of a contained rupture by exuberant fluid resuscitation. Endovascular coverage of the bleeding site with a thoracic endograft has emerged as the standard of care. Adjunctive obliteration of the retrograde false lumen filling from distal re-entry tears (eg, "candy plug," coil embolization, or Knickerbocker technique) may be necessary to achieve complete hemostasis after proximal TEVAR.8,9,10 Thankfully, unless no endovascular option exists, open surgical treatment of ruptured TBAD has all but vanished due to poor operative outcomes. In-hospital mortality in cases of TBAD with rupture ranges from 25% to 50%. Management of End-Organ Malperfusion in Complicated Acute TBAD Acute TBAD can result in obstruction to blood flow in any organ supplied by the involved segment of the aorta and its branches. For patients with malperfusion, the success of endovascular management is largely dependent on the location of the primary entry tear, the longitudinal extent of the dissection, and the impact of the dissection on branch vessel patency.11 In the most common scenario, the primary entry tear is located in zone 3 with variable propagation of the dissection both proximally (retrograde) and distally (antegrade). TEVAR is typically effective at achieving the dual objectives of covering the proximal entry tear and restoring, or at least improving, true lumen blood flow. If branch vessel obstruction persists after TEVAR, percutaneous stenting of branches to assure communication between the true lumen and the end organ is usually effective at restoring blood flow. By reducing the inflow to the false lumen at the primary entry tear, TEVAR is expected to reduce the pressurization of the false lumen with subsequent improvement in true lumen flow. There is a complex interplay between the size and location of the primary entry tear and the location, number, and size of the re-entry tears. The combination of a large proximal entry tear and limited (or no) exit tears has been associated with high false lumen pressurization and the risk of aneurysmal enlargement. Traditionally, branch vessel obstruction has been classified as either dynamic or static. Dynamic obstruction is the result of the variable pressurization of the false lumen during the cardiac cycle. It can be visualized with intravascular ultrasound (IVUS), which demonstrates the remarkable mobility of the dissection membrane. Static obstruction of branch vessels results from constant compression or thrombosis of the true lumen. Dynamic obstruction is estimated to be the dominant mechanism of ischemia in approximately 4 of 5 patients with malperfusion.11 If endovascular options are unavailable to treat malperfusion due to the absence of appropriate resources or personnel, a number of open surgical options may be enlisted. Open aortic septectomy via a left flank retroperitoneal exposure can effectively restore visceral and renal perfusion. Extremity ischemia can be treated with extra-anatomic bypass if endovascular options have failed or are unavailable. Trends and Outcomes in Tbad Over the past 20 years since the widespread use of TEVAR, the following trends in management of acute TBAD have been observed: increasing use of TEVAR in uncomplicated patients, decreasing open surgery, and decreasing reliance on optimal medical management alone from more than 75% to approximately 50%.12 These trends are based on the observation that TEVAR in combination with contemporary endovascular adjunctive techniques is remarkably effective in the treatment of malperfusion and rupture in the setting of acute TBAD. Approximately one-third of cases of acute TBAD are complicated. Overall, in-hospital mortality with acute TBAD is 12% to 14% with a three-fold increase in mortality in complicated/high risk patients.2,12,13 A number of predictors of mortality have been identified (Table 2). Mesenteric ischemia is a particularly ominous finding, with a nine-fold increased risk of death compared to patients with normal visceral blood flow. Table 2 Predictors of mortality in acute type B dissection.2 PREDICTORS MORTALITY ODDS RATIO Increasing age per decade 1.3 Female sex 1.4 Extremity ischemia 3.0 Periaortic hematoma 3.0 Aortic diameter > 5.5 cm 3.0 Acute renal failure 3.6 Hypotension/shock 6.4 Mesenteric ischemia 9.0 Long-Term Outcomes of Acute TBAD A seminal report from the International Registry of Acute Aortic Dissection (IRAD) provides important background data for evaluation of long-term outcomes after acute TBAD treated with TEVAR (n = 276) versus optimal medical management (OMT) (n = 853).14 In-hospital mortality was similar in patients managed with TEVAR versus OMT (10.9% vs 8.7%, P = .273). One-year mortality also was similar in both groups (8.1% TEVAR vs 9.8% OMT, P = .604). Aortic enlargement was observed in 62.7% of patients after TEVAR and 73.3% after OMT based on 5-year Kaplan-Meier estimates.14 The long-term effectiveness of endovascular treatment of acute TBAD with TEVAR is largely determined by both the longitudinal extent and the chronicity of the dissection. While malperfusion is a problem predominantly confined to the hyperacute and acute phases (ie, up to 14 days), it has been observed that remodeling (true lumen expansion and false lumen regression) of the aorta after TEVAR occurs almost exclusively in the segment that is covered by the endograft.15,16,17,18,19 In addition, temporal changes in the structure and compliance of the dissection membrane have an important impact on long-term success. Aortic remodeling after TEVAR is a continuous process.20 Acute dissections remodel more rapidly and more often than chronic dissections,21 and remodeling is greater in more proximal aortic segments.18 For dissections confined to zones 2 through 5 (from the left common carotid to the celiac artery), simple TEVAR with or without left subclavian artery revascularization is usually effective at achieving both long-term success as measured by complete false lumen remodeling and avoidance of additional procedures.22,23 For acute TBAD involving zone 1, either endovascular revascularization or extra-anatomic surgical debranching of the left common carotid and left subclavian arteries can achieve equally durable long-term results. But in patients managed medically or in TEVAR patients with dissection involving the visceral aorta and the aortic bifurcation (zones 6-11), the long-term outcomes of acute and subacute TBAD are dominated by the inexorable enlargement of the untreated aortic segments. At least one-third of survivors of acute TBAD will require subsequent intervention of the untreated aortic segment, mostly as a result of pressurization of the false lumen that causes total aortic diameter expansion. While TEVAR for chronic dissection with progressive false lumen enlargement has been associated with low perioperative risk, Mani et al. reported that total aortic diameter was reduced in only 50% of patients following TEVAR for chronic aortic dissection.15 Others have reported similar disappointing long-term outcomes following conventional TEVAR.24,25 Thus, substantial efforts are underway to improve the long-term outcomes by procedural modifications to the endovascular treatment of acute TBAD. At least three strategies have developed with sufficient momentum to warrant review here: (1) techniques designed to enlarge the true lumen and aggressively obliterate the false lumen, (2) techniques to induce false lumen thrombosis and advance remodeling, and (3) improvements in endograft design to reduce long-term adverse events. OMT vs TEVAR in acute uncomplicated TBAD It is widely believed that thrombosis of the false lumen and subsequent remodeling of dissected aorta is likely associated with improved survival.15,23,26,27 While OMT is effective in the near-term, it has not prevented aneurysmal degeneration of the dissected aorta. The INSTEAD trial randomly assigned patients with uncomplicated, subacute (> 14 d) TBAD to OMT (n = 68) or OMT and TEVAR (n = 72).28 Initial results showed no difference in all-cause mortality at 2 years, but 5-year data confirmed improved survival and aortic remodeling in the TEVAR group.29 It should be noted that the INSTEAD trial specifically excluded patients < 14 days and may not reflect outcomes in hyperacute or acute-phase patients. The ADSORB trial randomly assigned patients with acute (< 14 days) TBAD to OMT (n = 31) or OMT plus TEVAR (n = 30). One-year results showed improved remodeling of the thoracic aorta covered by an endograft,30 and long-term results are pending. Of note, perioperative paraplegia, stroke, and death were not observed in ADSORB.30 One major stroke and two cases of spinal cord injury (SCI) were reported in the INSTEAD trial.28 These data support the concept of employing TEVAR in selected uncomplicated TBAD to reduce the incidence of late aneurysmal change. For TEVAR to play a role in these patients, it must be accomplished with minimal morbidity, which from a practical standpoint means avoiding stroke and SCI. There are insufficient data to support the widespread adoption of TEVAR for uncomplicated TBAD at this time. A large randomized multicenter trial would be required to definitively answer this question. Techniques to Prevent Aneurysmal Degeneration of Tbad Knickerbocker The "knickerbocker" technique was first described in 2014 in three patients with subacute or chronic aortic dissections .31 All three patients had either rapid expansion or frank rupture from aneurysmal enlargement of the false lumen. Following placement of a thoracic endograft that was oversized 10% to 15% larger than the total aortic diameter, persistent hemorrhage occurred due to retrograde flow in the false lumen from a re-entry tear. Given the urgency, the authors elected to rupture the dissection membrane with a compliant balloon in the midportion of the endograft and thereby expand the endograft to obliterate the false lumen and prevent retrograde exsanguination. The endovascular technique was designed to mimic a similar open transsternal procedure reported by Rosselli et al. or a subxiphoid technique by Konings.32,33 The authors eventually contributed to the design of a commercial thoracic endograft with a double-tapered tubular design and a bulbous middle segment (similar to the shape of knickerbocker pants) that could be intentionally expanded to obliterate the false lumen and prevent back flow.34 The device has not gained widespread use but established the feasibility of balloon membrane rupture to eliminate the false lumen, a technique that would be subsequently modified by others to achieve more complete treatment of TBAD using the STABILISE technique.35,36,37,38,39,40,41,42,43,44,45,46,47 Figure 2 Illustration of the Knickerbocker technique. (A) Type B aortic dissection with a large proximal entry tear leading to bleeding in the chest. (B) After TEVAR, the proximal entry tear is covered but distal false lumen backflow persists. (C) Despite covering the entire length of the descending thoracic aorta, there is persistent bleeding via false lumen filling. (D) Inflating a compliant balloon within the endograft intentionally ruptures the dissection membrane. (E) The expanded endograft prevents backflow into the false lumen aneurysm and eliminates the source of intrathoracic hemorrhage (X). TEVAR: thoracic endovascular aortic repair; TL: true lumen; FL: false lumen; TBAD: type B aortic dissection Illustration of the Knickerbocker technique Petticoat An alternative strategy to reduce the incidence of late treatment failures following TEVAR for TBAD relies on a composite device with a covered proximal component and bare metal distal component that is extended through the visceral segment (zones 6-8) to expand the true lumen and induce total aortic remodeling. Nienaber introduced the term "provisional extension to induce complete attachment after stent-graft placement in type B aortic dissection" (PETTICOAT) in 2006 to describe the use of bare metal self-expanding stents in the visceral aortic segment in 12 patients with persistent malperfusion despite proximal aortic endografting .48 The addition of the bare metal stent was uniformly effective in relieving acute malperfusion. Figure 3 (A) Acute type B aortic dissection. (B) Following proximal thoracic endografting, there is persistent retrograde flow in the false lumen. (C) Bare metal PETTICOAT self-expanding stent improves true lumen blood flow but does not prevent false lumen filling. (D) Intentional rupture of the dissection membrane with a compliant balloon results in obliteration of the false lumen. (E) The balloon is sequentially inflated throughout the entire thoracic and abdominal aorta. (F) The false lumen is completely eliminated by intentional rupture of the dissection membrane. (A) Acute type B aortic dissection Following endograft Since its introduction, the technique has been used with increasing enthusiasm with the goal of improving late aortic remodeling in the visceral aortic segment. One of the largest trials (STABLE) evaluated the Zenith Dissection Endovascular System (Cook, Inc.), consisting of a conventional proximal endograft combined with bare metal Z-stents extending through the abdominal aorta.49 This prospective, single-arm, multicenter study enrolled 86 patients at sites in Europe, Australia, and the United States from 2007 to 2012. All patients had acute or subacute dissections (< 90 days), and 30-day all-cause mortality was 4.7%. At 5 years, freedom from all-cause mortality was 75% and freedom from aorta-related mortality was 85%.50 Complete thrombosis of the false lumen in the thoracic aorta was observed in approximately 70% (30/44) of patients but in < 10% (4/46) in the abdominal aorta.50 Approximately 30% required reintervention within 5 years. While these results represent incremental improvement over standard TEVAR without visceral aortic bare metal stenting, it was disappointing that remodeling in the uncovered aortic segments was not more impressive. Despite dozens of publications reporting the results of the PETTICOAT technique, there are no head-to-head or randomized comparisons between conventional proximal TEVAR and TEVAR plus visceral bare-metal stenting. Results of the PETTICOAT trials have been mixed. For example, Nienaber et al. reported improved remodeling of the abdominal aorta at the level of the celiac artery in patients treated with TEVAR plus E-XL bare stent (JOTEC) compared with TEVAR-only propensity-matched controls (complete false lumen thrombosis 54% versus 18%, P = .004).51 In contrast, Mascia et al. reported that a PETTICOAT using the Zenith bare stent system does not prevent long-term aneurysmal degeneration.52 Furthermore, there have been occasional reports of complications related to the bare stent, including stent migration, stent fracture, and misalignment.53,54,55 A Cochrane review of the long-term outcomes of the PETTICOAT was abandoned because the absence of randomized trials precluded definitive assessment of the technique's long-term utility.56 A meta-analysis by Qui et al. that included 914 patients in eight observational studies reported no difference in overall aorta-related mortality or complete false lumen thrombosis in the thoracic or abdominal segments. The bare stent group did have fewer stent-graft-induced new entry tears and less frequent reintervention.57 In summary, it appears that the extension of a bare metal stent in the abdominal aorta following proximal endografting is clearly beneficial in the acute setting because it improves visceral perfusion. The benefit of the PETTICOAT technique for reducing long-term adverse aortic events remains unproven. STABILISE Technique In an effort to reduce retrograde false lumen filling after proximal thoracic TEVAR, Hofferberth et al. in 2014 introduced the STABILISE concept (Stent-assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair).47 In this technique, a proximal endograft is placed in the thoracic aorta to cover the primary entry tear and a bare-metal "dissection" stent is extended through the visceral segment into the infrarenal aorta. In a deviation from the usual PETTICOAT technique, which depends entirely on the passive outward force of the self-expanding bare stent for compression of the false lumen, a compliant balloon is used to rupture the dissection membrane beginning in the thoracic endograft and extending to the distal extent of the bare stent.47 This technique effectively creates a single aorta channel and eliminates the false lumen. The chief drawback of this technique is fear of frank aortic rupture. In a search of all reported cases in the literature, there is only a single example of contained rupture of the infrarenal aorta, which was salvaged with a conventional EVAR device.58 The chief benefit of the STABILISE technique appears to be markedly improved remodeling of the abdominal aorta. Zhong et al. reported complete remodeling of the thoracic aorta in 100% (11/11) and of the abdominal aorta in 83% (9/11), which far exceeds historical controls.58 Others have reported similar results in both the acute and chronic setting using the STABILISE teichnique.35,37,39,43,59,60 Some have recommended more aggressive use of distal stenting and endografting in the infrarenal and iliac segments to cover all identifiable reentry tears. These reports suggest improved remodeling of the abdominal aortoiliac segment at the potential expense of increased SCI.61,62,63 False Lumen Embolization An alternative strategy to reduce false lumen enlargement long-term relies on a variety of techniques to induce thrombosis of the false lumen. In the original "candy plug" technique, a modified endograft component (eg, GORE EXCLUDER cuff) was released in the false lumen adjacent to a proximal true-lumen TEVAR with the goal of occluding flow in the false lumen.10 A second-generation device was produced commercially exclusively for this purpose.9 Pellenc et al. reported satisfactory results of false lumen embolization with Amplatzer plugs and conventional coils in 27 patients with chronic TBAD.64 Thrombosis of the false lumen was observed in 22/27 patients, including two cases of spinal cord ischemia despite spinal drainage. Others have reported the use of patent foramen ovale or atrial septal defect occluders, coils, and glue in addition to endovascular stenting of the true lumen with satisfactory short-term results.65 Exercise Following TEVAR As with other surgical conditions, increasing emphasis is placed on patient-centered outcomes. One important consideration in patients after treatment for TBAD is guidance regarding appropriate activity. While activities that lead to sudden spikes in blood pressure clearly should be avoided (eg, bench press with closed glottis), evidence is scarce for guiding clinicians in making rational recommendations. A recent survey of IRAD members favors aerobic activities to maintain overall cardiovascular fitness while avoiding highly stressful ballistic training that could be hazardous.66 Cerebrospinal Fluid Drainage Cerebrospinal fluid drainage (CSFD) during and after procedures that interfere with spinal cord blood flow has been widely used for 40 years to reduce the incidence of SCI. During the last several years, it has become apparent that the low incidence of SCI after TEVAR (< 5%) and the known risks associated with CSFD (eg, epidural hematoma, subarachnoid hemorrhage, malfunction, and infection) favor therapeutic CSFD over prophylactic drainage in most cases.67 Permissive hypertension may have a more beneficial impact on relieving postoperative paraparesis than prophylactic CSFD.67 Summary TEVAR is the standard of care for the treatment of acute complicated TBAD and selected patients with high-risk features. TEVAR effectively manages both rupture and malperfusion in most patients with acute TBAD without the need for secondary intervention. TEVAR is being employed more frequently in uncomplicated TBAD with the caveat that periprocedural risks of paraplegia and stroke must approach zero to justify this "prophylactic" strategy. The long-term outcomes from proximal endografting alone have been disappointing due to continued aneurysmal expansion in the untreated aortic segment occurring in 30% to 50% of patients within 5 years. A variety of other strategies have been explored including the PETTICOAT and STABILISE techniques to reduce the need for secondary interventions to prevent aneurysm formation. Key Points There is a new classification system that resolves deficiencies of the DeBakey and Stanford systems. It is recognized that thoracic endovascular aortic repair (TEVAR), the standard of care for treatment of complicated type B aortic dissection (TBAD), fails to effectively prevent aneurysmal degeneration in the untreated aortic segments. There is increasing use of TEVAR in uncomplicated TBAD despite the absence of definitive proof of efficacy. A variety of techniques and devices have emerged to improve the long-term outcomes of TBAD. 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Results of a new endovascular repair stabilise for aortic dissections in marfan patients. Sang Thrombose Vaisseaux. 2019 Sep-Oct;31 (5 ):188-94. doi: 10.1684/stv.2019.1080 41 Fouquet O, Dang Van S, Ammi M, Daligault M, Baufreton C, Picquet J. STABILISE Technique via a Transapical Approach to Repair Residual Type A Aortic Dissection. Aorta (Stamford). 2021 Aug;9 (4 ):161-164. doi: 10.1055/s-0041-1729851 34560805 42 Kahlberg A, Mascia D, Bertoglio L, et al. New technical approach for type B dissection: from the PETTICOAT to the STABILISE concept. J Cardiovasc Surg (Torino). 2019 Jun;60 (3 ):281-288. doi: 10.23736/S0021-9509.19.10904-4 43 Mascia D, Rinaldi E, Kahlberg A, et al. The STABILISE technique to address malperfusion on acute-subacute type B aortic dissections. J Cardiovasc Surg (Torino). 2022 Apr;63 (2 ):131-136. doi: 10.23736/S0021-9509.22.12249-4 44 Melissano G, Bertoglio L, Rinaldi E, et al. 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PMC10000327 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1172 VoR Review Dynamic Imaging of Aortic Pathologies: Review of Clinical Applications and Imaging Protocols Osztrogonacz Peter MD [email protected] 12 Berczeli Marton MD 12 Chinnadurai Ponraj MBBS, MMST 13 Chang Su-Min MD 1 Shah Dipan J. MD 1 Lumsden Alan B. MD 1 1 Houston Methodist Hospital, Houston, Texas, US 2 Semmelweis University, Budapest, Hungary 3 Siemens Medical Solutions USA Inc., Malvern, Pennsylvania, US CORRESPONDING AUTHOR: Peter Osztrogonacz, MD Houston Methodist Hospital, Houston, Texas, US; Semmelweis University, Budapest, Hungary [email protected] 07 3 2023 2023 19 2 414 15 12 2022 15 12 2022 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See The past decade has seen significant advances in dynamic imaging of the aorta. Today's vascular surgeons have the opportunity to choose from a wide array of imaging modalities to evaluate different aortic pathologies. While vascular ultrasound and aortography are considered to be the bread and butter imaging modalities, newer dynamic imaging techniques provide time-resolved information in various aortic pathologies. However, despite growing evidence of their advantages in the literature, they have not been routinely adopted. In order to understand the role of these emerging modalities, one must understand their principles, advantages, and limitations in the context of various clinical scenarios. In this review, we provide an overview of dynamic imaging techniques for aortic pathologies and describe various dynamic computed tomography and magnetic resonance imaging protocols, clinical applications, and potential future directions. dynamic imaging dynamic CTA dynamic MRA 4D flow MRI aorta aortic imaging diagnostic imaging Alan B. Lumsden receives research support from W. L. Gore & Associates, CorMatrix Cardiovascular, Silk Road Medical, and Cook Medical. He also consults with Boston Scientific, W. L. Gore & Associates, Siemens, Medical Metrics, Nova Signal, Intact Vascular, Karl Storz, Avail Medsystems, AneuMed, Silk Road Medical, Hemostemix, and KOL BioMedical and is a shareholder in Hatch Medical. Ponraj Chinnadurai is a senior staff scientist at Siemens Medical Solutions USA Inc. The other authors have no competing interests to declare. pmcIntroduction Dynamic imaging is a rapidly evolving yet not fully adopted technique in the realm of medical imaging modalities. Most aortic pathologies have a dynamic component, such as aortic dissection, and any imaging technique must be nimble enough to capture this dynamic nature--not only to enable better diagnosis but also to aid in determining optimal treatment options. To account for cardiac motion-related artifacts, especially in the ascending aorta and aortic arch, an electrocardiogram (ECG)-gated imaging protocol typically is performed. The word "dynamic" in dynamic imaging can be broadly interpreted as introducing time as the fourth dimension to evaluate the dynamics of contrast enhancement in the aorta--for example, time-resolved angiography. In addition, such novel dynamic imaging techniques can enable one to assess and quantify the direction, velocity, and volume of blood flow to impact clinical decision-making, patient management, and optimal post-interventional surveillance. Most cardiovascular imaging modalities have a dynamic component, including vascular ultrasound with contrast enhanced ultrasound, echocardiography, intravascular ultrasound, x-ray angiography, dynamic computed tomography angiography (d-CTA), and dynamic magnetic resonance angiography (MRA), such as 4-dimensional (4D) flow magnetic resonance imaging (MRI). Although each of the above-mentioned modalities can provide "dynamic" information during the evaluation of aortic pathologies, we limit the scope of this article to discussing the three most commonly used noninvasive dynamic 3D cross-sectional imaging techniques: dynamic CTA, dynamic MRA, and 4D flow MRI. Herein we provide an overview of dynamic aortic imaging techniques, describing various CT/MRI protocols, clinical applications, and potential future prospects. Imaging Modalities and Protocols Dynamic CT Angiography Like conventional CTA imaging, d-CTA involves acquiring a series of CTA datasets (approximately 5-12 scans) across different points of the contrast enhancement curve after a bolus of iodinated contrast injection .1 In addition, ECG-gated CTA can be used to evaluate cardiac, ascending aortic, and arch pathologies by acquiring a series of CTA datasets (approximately10 scans) across different points of the cardiac cycle.2 These two techniques also can be combined to provide time-resolved contrast kinetics and ECG gating for cardiac motion, especially in the setting of post endograft surveillance in the ascending aorta and aortic arch.3 The technical details and our institutional CT aortic imaging protocols are summarized in Table 1. Figure 1 Delayed phase computed tomography (CTA) and dynamic CTA (d-CTA) images across multiple timepoints. During d-CTA, approximately 10 to 15 images are acquired in different timepoints after the contrast bolus to assess the exact type of endoleak. In this particular case, the most informative image is acquired around 24 seconds after contrast injections (panel J). The aneurysm sac (white * sign) is filled by the right lumbar artery (white arrow). In comparison, the image acquired with standard CTA in the delayed phase falls behind the acquired d-CTA images in terms of identifying the source of endoleak. Dynamic CTA images across multiple timepoints Figure 2 Comparison of arterial and delayed phases of triphasic computed tomography (CTA) with dynamic CTA findings. Compared to triphasic CTA, dynamic CTA is superior in identifying endoleak following endovascular aneurysm repair (EVAR). In this particular case, neither the arterial (A) nor the delayed (2 E) CTA phases were able to support endoleak as the underlying cause of progressive aneurysm sac growth following EVAR. In contrast, dynamic endoleak (panels B-D, F-H) was capable of showing the endoleak and the supplying inferior mesenteric artery (panel F, white arrow). Triphasic CTA compared with dynamic CTA Figure 3 Time attenuation curve (TAC) of the aorta and the site of endoleak pertaining to Figure 2 dynamic CTA (d-CTA). The TAC of the d-CTA shows a significant delay (20 seconds) in the peak of the Hounsfield unit between the region of interest (ROI) placed in the aorta (red deg sign, ROI-1) and ROI placed at the site of the endoleak (yellow # sign, ROI-2), suggesting the sac filling from the inferior mesenteric artery toward the aneurysm sac rather than direct filling from the aorta. Time attenuation curve in dynamic CTA-type 2 endoleak detection Table 1 Dynamic computed tomography angiography imaging protocol for aortic endoleak detection. CT: computed tomography; CTA: computed tomography angiography; d-CTA: dynamic CTA DYNAMIC CTA IMAGING PROTOCOL FOR AORTIC ENDOLEAK STEPS DETAILED STEPS 1 Patient positioning Supine 2 Peripheral vein access Right/left upper extremity 3 Topogram and noncontrast CT imaging acquisition Sn-100 T in filter to reduce radiation exposure 4 Timing bolus to check contrast arrival time 10-20 mL contrast injection followed by 50 mL saline at 3.5-4 mL/min flow rate, region of interest in aorta 5 Distribution and scan number planning Choose DynMulti4D menu from the pop-up menu, plan distribution and scan number based on timing bolus and findings on previous studies 6 Optimize imaging parameters To reduce exposure, optimize kV, scan range, etc. 7 Contrast injection for d-CTA acquisition 70-80 mL contrast injection followed by 100 mL saline at 3.5-4 mL/min flow rate 8 Start d-CTA acquisition Use delay time determined by the timing bolus 9 Parameters for d-CTA scan 10-12 scans, tube voltage: 70-100 kV, tube current: 150 mAs, rotation time: 0.25 s, scan duration: 39 s, slice thickness: 0.7-1 mm, field of view (z-axis) : 23-33 cm Dynamic Magnetic Resonance Imaging Unlike CTA imaging, MRI can provide better insights into aortic pathologies by imaging vessel wall characteristics without any additional radiation exposure. However, its clinical utilization is still evolving due to relatively longer acquisition times, the need for a dedicated setup, a steeper learning curve, and understanding and optimizing multiple MR imaging sequences. The technical details and our institutional MR aortic imaging protocols are summarized in Table 2. In addition to conventional imaging sequences, the 4D flow MRI sequence deserves a special mention because it is a time-resolved 3D phase contrast MRI sequence capable of providing quantitative and qualitative flow information across any segment of the aortic lumen . It does not require any additional contrast agent, although having an on-board contrast agent increases the signal-to-noise ratio. Table 2 Dynamic magnetic resonance imaging protocol. MRI: magnetic resonance imaging; DICOM: Digital Imaging and Communications in Medicine; HASTE: half-fourier acquisition single-shot turbo spin-echo; PACS: picture archiving and communication system; SSFP: steady-state free precession; TWIST: time-resolved angiography with stochastic trajectories; VIBE: volumetric interpolated breath-hold examination DYNAMIC MRA PROTOCOL STEPS DETAILED STEPS 1 Patient positioning Supine 2 Peripheral vein access Right/left upper extremity 3 Acquiring mask or later subtraction Chest-abdomen noncontrast full-resolution image 4 Contrast administration Gadolinium: 30-40 mL contrast material + 50 mL saline injection to wash out the contrast agent from the periphery Ferumoxytol (feraheme): 3 mL with 27 mL saline followed by 50 mL saline flush 5 Contrast passage visualization Done by acquiring scan 6 Regular sequences are acquired for dynamic MRI scan SSFP cine to evaluate dynamic vs static obstruction in TBAD HASTE, bright blood SSFP, 3D contrast-enhanced MRA to evaluate aortic morphology, TWIST for time resolved MRA, T1 VIBE for steady state imaging, 4D flow for qualitative and quantitative flow evaluation 7 4D flow MRI VENC 150-200 cm/s, acquisition time 7-12 min, free breathing 8 Send acquired data to database Acquired data is sent to the institutional cloud-based imaging database (PACS) 9 Image analysis Using DICOM viewer connected to the institutional PACS Figure 4 Qualitative analysis of type-B aortic dissection using magnetic resonance imaging (MRI). The contrast-enhanced MRA sequence (A) gives information on the site of the primary entry tear (white arrows), while the TWIST sequence shows the intimal flap and the directionality of false lumen filling (B). 4D flow MRI sequence (C-E) may complete the assessment of aortic dissection with color-coded velocity mapping, which is potentially able to uncover the tear where the false lumen is filling through (white arrows, C-E). Imaging of type-B aortic dissection with multiple MRI sequences Figure 5 Quantitative flow evaluation of true lumen and false lumen using 4-dimensional (4D) flow magnetic resonance imaging (MRI). 4D flow MRI provides quantification of flow parameters depicted by the marked areas on panels B-E. The flow volume is displayed in a graph (A) where the y-axis represents the flow volume (mL/s) through the marked area and the x-axis represents time in milliseconds. In aortic dissection, the true lumen (A: red line, D: red outline) and the false lumen (A: green line, E: green outline) can be interrogated, and the entire flow volume (A: yellow line, C: yellow outline) can be determined. Flow evaluation in the true and false lumen with 4D flow MRI Clinical Applications of Dynamic Aortic Imaging Aortic pathologies cover a broad spectrum of vascular diseases of the aorta, spanning from the aortic valve to the distal abdominal aorta. In this section, we provide a descriptive overview of clinical applications of the dynamic imaging technique across various aortic pathologies and its impact on treatment planning and guidance based on our early clinical experience. 1. AORTIC Valvular Disease In developed countries, aortic stenosis (AS) ranks as the most common valvular heart disease, occurring in 12.4% of elderly patients.4,5 Transthoracic echo (TTE) is considered to be the mainstay of diagnosis and classification of disease severity, providing information on peak jet velocity, mean transvalvular pressure gradient, and aortic valve area. Contrast-enhanced CTA imaging is also a standard-of-care imaging technique to facilitate better aortic morphometry and plan for potential transcatheter therapies. In the setting of AS, cardiac MRI is performed in select situations to study any other associated cardiac anomalies and to provide better noninvasive hemodynamic information. Adriaans et al.6 compared TTE and 4D flow and found the latter to improve concordance between AS parameters regarding peak jet velocity, mean transvalvular pressure gradient, and aortic valve area. The study suggested the potential of 4D flow MRI as a comprehensive noninvasive quantitative technique, especially in patients with inconsistent findings on TTE. Aortic regurgitation (AR) can occur with or without AS, and TTE is the gold standard modality for diagnosis and evaluation based on current guidelines.7,8 CTA adds the anatomical information required for invasive treatment planning. In addition, cardiac MRI is considered to be a complementary imaging technique, although it gives more accurate information on left ventricle volume, mass and function as well as aortic dilatation compared with TTE.9,10 2. Acute Aortic Syndrome Acute aortic syndrome is an umbrella term referring to aortic dissection, intramural hematoma, and penetrating aortic ulcer. All three conditions are considered potentially lethal and may overlap with each other. Since acute type A dissection presents as an imminent life-threatening condition, MRI currently is not considered an option for preoperative planning given its time-consuming nature, nor is dynamic CTA due to its limited field of view. 2.1 Type-B Aortic Dissection Type-B aortic dissection (TBAD) occurs when a tear develops in the intimal layer distal to the origin of the innominate artery,11 and blood flow enters the space between the intimal and medial layers of the aorta, creating true and false lumen throughout the length of the affected aortic segment. The intimal flap may compromise blood supply via the aortic branches by causing either dynamic or static obstruction. In general, standard operative strategy for complicated TBAD includes primary entry tear coverage with a stent graft to facilitate false lumen collapse and positive aortic remodeling, although dynamic imaging may uncover a more distal tear as the one supplying the false lumen. Failure of culprit fenestration coverage could lead to subsequent interventions, increasing the risk for perioperative morbidity such as access-related complications, progression of aortic dissection, or spinal cord ischemia. Moreover, dynamic imaging could also aid in discerning between dynamic and static obstruction of visceral vessels, consequently affecting operative planning. While d-CTA is capable of the latter, given the limited field of view, it does not allow for imaging of the entire aorta, which excludes d-CTA from initial TBAD assessment. In fact, it can be preserved for follow-up imaging to address specific questions, such as determining residual static versus dynamic occlusion of the aortic branches. Overall, several studies have been published regarding 4D flow MRI in TBAD patients, yet each of them lacks long-term follow-up and an appropriate number of cases.12,13,14,15,16 Apparently, 4D flow MRI seems comparable to triphasic CTA in terms of fenestration detection in TBAD patients based on the study conducted by Allen et al.12 Another study concluded that 4D flow MRI image quality is comparable to CTA for TBAD assessment.13 A third paper evaluated false lumen pressure analysis in chronic TBAD patients and identified false lumen ejection fraction and absolute pressure difference between distal false lumen and aortic root as independent factors for aortic growth.14 Ruiz-Munoz et al. examined false lumen flow dynamics and biomechanics and identified in-plane rotational flow, pulse wave velocity, and false lumen thrombus as factors positively related to aortic growth in chronic aortic dissection patients.16 On the whole, the concept of 4D flow MRI imaging in TBAD patients seems to be established ; however, further longitudinal large cohort studies are required to assess its place in TBAD management. Dynamic MRA could be helpful to determine the flow directionality in the false lumen, but it does not provide additional information compared with 4D flow MRI. Kinner et al. compared dynamic MRA (TWIST sequence) to high-resolution contrast-enhanced MRA in acute aortic dissection patients. On one hand, they have found the latter as significantly more sensitive and even comparable to CTA in terms of image quality.17 On the other hand, dynamic MRA affected the treatment plan for 10 out of 19 patients, which underlines the importance of dynamic imaging in this particular aortic pathology . 2.2 Intramural Hematoma and Penetrating Aortic Ulcer Intramural hematoma (IMH) occurs when blood enters the intimal/medial layer without visible entry tear. Penetrating aortic ulcer (PAU) develops in the aortic wall as a focal outpouching to the internal elastic lamina due to atherosclerotic plaque erosion and inflammatory changes.18,19 In general MRI is an excellent modality to assess and follow IMH and PAU lesions,20,21 however the role of dynamic imaging is not yet established in the setting of these types of aortic pathologies. Although in theory dynamic imaging could provide additional information on the feeding vessel and blood pool in cases of acute/subacute IMH, further research is necessary to acquire sufficient evidence-based data. IMH is a dynamic phenomenon, thus addressing it with time-resolved imaging can help to better identify influencing factors. IMH has several imaging features, such as intramural blood pools, which are considered a benign prognostic factor and may favor conservative management.22 Berczeli et al. recently highlighted that d-CTA imaging can help in understanding the pathophysiology behind these blood pools by identifying flow direction and their source.23 3. Aortic Coarctation Aortic coarctation (CoA) is a congenital cardiovascular condition in which the aorta is narrowed, most commonly around the level of the ligamentum arteriosum.24 CoA is responsible for 5% to 7% of congenital heart disease cases and predisposes to hypertension, aortic insufficiency, aortic dissection, and aortic aneurysm.25,26 Based on the location of the narrowing, CoA is classified as preductal, ductal, or postductal, the latter being the most common type in adults.27 Treatment is based on pressure gradient through the stenosis and post-stenotic pressure loss.28 When the systolic pressure gradient exceeds 20 mm Hg, intervention is recommended according to current guidelines.26 The pressure gradient could be measured either by invasive catheterization or by TTE. 4D flow MRI offers a noninvasive alternative to measure flow proximal and distal to the coarctation in all three dimensions, addressing the shortcomings of the previous two modalities, namely invasiveness in case of catheterization and the lack of time-resolved 3D information on part of TTE. Additionally, 4D flow MRI provides information about the collateral flow as well.29 Riesenkampff et al. compared 4D flow MRI and catheterization, in terms of pressure measurement at 5 different locations on the aorta and concluded a good agreement between the two modalities, suggesting that 4D flow MRI could potentially replace invasive catheterization in the evaluation of CoA.26 Overall 4D flow MRI is a promising technique regarding CoA assessment, which may guide the perioperative management of patients with CoA in the future. 4. Thoracic and Thoracoabdominal Aneurysms The term "aneurysm" refers to a localized dilation involving all 3 layers of the vessel, which exceeds the normal caliber by more than 150%. The most common thoracic aortic aneurysms are located on the ascending aorta (40%), followed closely by descending thoracic aortic aneurysms (35%). The aortic arch (15%) and the thoracoabdominal localization (10%) are considered less frequent. Due to recent advancements in aortic graft development, in specific scenarios, the ascending aortic stent graft implantation offers a feasible alternative to open repair. However, follow-up of these grafts presents a challenge with traditional d-CTA, given the frequent occurrence of cardiac motion related artefacts. In these instances, dynamic electrocardiography-gated CTA offers a viable solution and optimizes imaging sensitivity for endoleak detection.3 The descending thoracic and abdominal aorta have not been studied extensively in terms of dynamic imaging, to date. Based on the data published on 4D flow MRI performed on ascending aortas, wall shear stress and oscillatory shear index (instantaneous WSS fluctuation) play an important role in ascending aorta dilation.30,31,32 These findings are probably applicable to the descending thoracic aorta, although further studies are required to explore the role of 4D flow MRI at the level of the descending thoracic aorta. 5. Abdominal Aortic Aneurysm The infrarenal aorta is considered the most common predilection location for aneurysmal disease.33 Endovascular aneurysm repair (EVAR) is the mainstay of infrarenal abdominal aortic aneurysm (AAA) treatment due to its superior perioperative survival rate compared to open surgical repair,34,35,36,37 type II endoleak (T2EL) being the most common endoleak following EVAR procedures.38 T2EL is caused by retrograde filling of the aneurysm sac after stent graft implantation, usually from lumbar branches and/or the inferior mesenteric artery (IMA). Although dynamic imaging may not provide additional information compared to triphasic CTA and MRA in the preoperative evaluation of infrarenal AAAs, it presents a unique option during the course of postoperative follow-up in terms of diagnosing and differentiating between the various types of endoleaks and determining the culprit vessel(s) feeding the aneurysm sac in the setting of T2EL.39 While triphasic CTA is able to assess aneurysm sac growth and suggests the type of endoleak, d-CTA has been reported as more accurate compared to triphasic CTA in terms of identifying the type of endoleak following an EVAR procedure.40,41,42 Additionally, Berczeli et al.42 demonstrated the applicability of d-CTA in intraoperative image guidance as well, underlining the versatility of this particular imaging modality. However, as tempting as it seems to perform d-CTA for routine follow-up after EVAR, in our day-to-day practice we tend to reserve it for cases where findings on triphasic CTA are inconclusive regarding the origin of the endoleak . 4D flow MRI offers an alternative to d-CTA for endoleak detection following EVAR. Although 4D flow MRI is considered inferior compared to traditional CTA in terms of spatial resolution, it can be improved with contrast administration.43 The combined functional and anatomical information acquired this way can aid in endoleak detection, treatment planning, and even in intraoperative image guidance. Sakata et al.44 compared CTA and 4D flow MRI in endoleak detection and found 4D flow MRI to be more sensitive in terms of endoleak identification. In fact, 4D flow MRI provides a plethora of information on intraluminal flow patterns, which could be used as predictors for certain aortic conditions, including aneurysm sac growth in T2EL. Flow analysis may contribute to a better understanding of T2EL and helps to identify the patient group that could benefit from T2EL repair. A recent retrospective single-center study used 4D flow MRI to identify parameters related to aneurysm sac growth in the setting of T2EL. First, they found higher initial peak flow velocity and amplitude of dynamics of blood flow in the persistent feeding vessel group after 1 year. Second, they found a correlation between aneurysm sac expansion and initial higher amplitude of dynamics of blood flow.45 Van der Laan et al.46 examined MRI plus dynamic MRA and found it to be superior to MRI in endoleak detection, although further studies have not been conducted for this application of dynamic MRI. High-resolution MRA combined with 4D flow MRI has an advantage over dynamic CTA by being able to image the whole aorta with no radiation burden while allowing for the detection of flow patterns and wall shear stress. However, the sensitivity of 4D flow MRI in T2EL detection is yet to be determined. 6. Aortic Occlusion Although no data currently exists in the literature on dynamic imaging in aortic occlusion patients, 4D flow MRI could potentially allow for quantitative collateral flow assessment in chronic aortic occlusion to determine the necessity or extent of aortic reconstruction. In comparison, dynamic CTA and dynamic MRA may not be suitable for functional assessment of aortic occlusion since they do not provide an opportunity for in-depth flow analysis. Future Directions Although vascular ultrasound and digital subtraction angiography are the most frequently used dynamic imaging tools, these modalities lack 3D visualization. In contrast, dynamic CTA, dynamic MRA, and 4D flow MRI offer 3D-rendered time-resolved alternatives. Obviously, each of these modalities have disadvantages, but the majority of them have already been addressed. For example, dynamic CTA is associated with a moderate amount of radiation burden, which could potentially be significantly reduced in the future with the latest generation CT scanners (for example, photon-counting CT technology). Also, 4D flow MRI acquisition must become faster and more accurate to offer an alternative to CTA in acute cases and to reach widespread recognition. Additionally, the general knowledge of this modality must be established to take full advantage of it. One approach to these challenges could be the introduction of compressed sensing, more robust automated segmentation, and utilization of computational fluid dynamics with adaptive mesh refinement.47 Currently, dynamic imaging in general is used sporadically without a uniform disease-tailored protocol, which is natural given the lack of large cohort longitudinal trials. Therefore, more large-scale studies are required to establish evidence in dynamic imaging of the aorta. Time-resolved cross-sectional imaging modalities carry great potential and may open the door to a new era in vascular surgery, where we can offer patient-tailored treatment for a variety of aortic pathologies to an extent never seen before. Key Points Dynamic computed tomography angiography (CTA), dynamic magnetic resonance angiography (MRA), and 4-dimensinal (4D) flow MRI are dynamic imaging techniques enabling 3D cross-sectional imaging of the aorta. Dynamic CTA is an established imaging technique that proved to be the most suitable for identification and classification of endoleaks during post endograft surveillance. Although the routine clinical utilization of dynamic MRA and 4D flow MRI in aortic conditions is still evolving, they carry an enormous potential by allowing for flow pattern analysis along the entire aorta. The capability to image the entire aorta and provide qualitative and quantitative flow analysis are the main advantages of dynamic MRA and 4D flow MRI over dynamic CTA, which operates with a limited field of view. Competing Interests Alan B. Lumsden receives research support from W. L. Gore & Associates, CorMatrix Cardiovascular, Silk Road Medical, and Cook Medical. He also consults with Boston Scientific, W. L. Gore & Associates, Siemens, Medical Metrics, Nova Signal, Intact Vascular, Karl Storz, Avail Medsystems, AneuMed, Silk Road Medical, Hemostemix, and KOL BioMedical and is a shareholder in Hatch Medical. Ponraj Chinnadurai is a senior staff scientist at Siemens Medical Solutions USA Inc. The other authors have no competing interests to declare. 1 Berczeli M, Chinnadurai P, Chang SM, Lumsden AB. Time-Resolved, Dynamic Computed Tomography Angiography for Characterization of Aortic Endoleaks and Treatment Guidance via 2D-3D Fusion-Imaging. 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PMC10000328 | J Cogn J Cogn 2514-4820 Journal of Cognition 2514-4820 Ubiquity Press 10.5334/joc.262 VoR Review Article Cognition Assessment Technologies on Deaf People Guerrero-Arenas Coral I. [email protected] 1 Osornio-Garcia Fernando Uristy 1 1 Departamento de Ingenieria en Sistemas Biomedicos, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, MX CORRESPONDING AUTHOR: Coral I. Guerrero-Arenas Departamento de Ingenieria en Sistemas Biomedicos, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, MX [email protected] 08 3 2023 2023 6 1 1813 9 2022 17 1 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See In recent years there has been a growing interest in research about the different ways of processing and consolidating cognition in deaf people. It is known that hearing loss can lead to differences in some executive functions like control inhibitory or working memory. This literature review describes executive functions in deaf people and how they could be evaluated through technological devices complementing traditional assessments, like neuropsychological batteries. We identified biometric devices, digital and physical interfaces, and software from the literature, whose goal is to design or adapt technology to assess some cognition domains in several ways. The results of the review suggest the need to understand the cognitive phenomenon that significantly impacts the context of deaf people; moreover, it becomes relevant as a line of research in the Cognitive Science of Hearing. Using technologies to measure them and gain a better understanding of cognition in deaf people may provide possibilities for designing or adapting targeted educational or therapeutic strategies. Deafness executive functions technology Consejo Nacional de Ciencia y Tecnologia, CONACYT 10.13039/501100003141 This research has been supported by a postdoctoral fellowship from the Consejo Nacional de Ciencia y Tecnologia, CONACyT, Mexico, awarded to Dr. Coral I. Guerrero-Arenas. pmcIntroduction The executive function (EF) construct encompasses a set of higher-order cognitive abilities such as the organizational, control, and self-regulation skills necessary for goal direction (Cristofori, Cohen-Zimerman & Grafman, 2019; Figueras et al., 2008). It has been reported that people with hearing loss may have a higher risk factor for developing and consolidating some of these executive functions (Mason et al., 2021; Conway, Pisoni & Kronenberger, 2009; Pisoni & Cleary, 2003). No agreement yet on the consequences of the hearing loss itself or the social and personal restrictions are underlying the barrier to communication with others (Corina & Singleton, 2009) or in addition to other factors such as the etiology of hearing loss and sociocultural context. Particularly some researchers have exposed differences in attention skills (Bavelier et al., 2000a; Hauser et al., 2007; Thakur et al., 2019; Tharpe et al., 2008; Zeni et al., 2020) in working memory tasks (Burkholder & Pisoni, 2003; Pisoni & Cleary, 2003), inhibitory control, (Mason et al., 2021), and sensorimotor synchronization (Petry et al., 2018; Tranchant et al., 2017). However, there is evidence for some auditory deprivation-dependent brain changes that may be related to functional and adaptive behaviors (Kral et al., 2016). Indeed, it has been hypothesized that hearing loss has effects beyond auditory processing and may affect cognitive functions related to sequentially and temporality since hearing is the primary sensory pathway for perceiving high-level sequential patterns that change in time rather than space (Conway et al., 2009). That is, that audition leads to the establishment of temporal ordering that underlies expectation and anticipation, what comes before and what happens next? For example, a subdomain of working memory attends to this temporality, as will be discussed below. It appears that deaf individuals, especially those who have not acquired language early, there may be more difficult in consolidating functions related to learning sequentially. On the other hand, and in contrast to the above, it seems that once the sign language is consolidated there are increases in subdomains of some functions, for example, in peripheral attention processes, that underlie inhibitory control (Bosworth & Dobkins, 2002), this makes sense given that a visuospatial language such as sign language develops spatially, supported more by visual and proprioceptive processes. This is consistent with the Enhanced Hypothesis proposed by Rodger et al., (2021) and Sidera et al., (2017) which states that in the absence of hearing the visual system would have a more significant visual function. However, Dye, Hauser & Bavelier (2009) suggest that hearing deprivation is not a causal factor for presenting difficulties in cognitive processes, such as attention, but that these may be a consequence of other factors that have nothing to do with deafness per se since it is essential to take into account aspects such as the etiology of deafness, sociocultural factors, the age of acquisition of a communicative system, and even the modality in which this is consolidated, that is, whether it is a sign language or an oral language. Even the results that show differences in some cognitive domains are different in children and adults because the consolidation of neurodevelopmental milestones seems to depend largely on the acquisition of a communicative system, without conclusive evidence on the issue, mainly because of the dynamism that characterizes cognition and that must be considered in technological development. Technological development has allowed converging lines of research related to the deaf population, emphasizing on time advance related to assistive technologies, especially those focused on communication. Assistive technologies are defined as those developments, software, or products that allow for to increase, maintain, or improve some functional capabilities in people with disabilities, for example, prosthetic pieces, hearing aids, screen readers, or wheelchairs, among others. Its main function is to assist the person to be as independent as possible. Most of the literature linking technology and deafness is focused on these types of devices, especially those developments to reduce communication challenges (Landolfi et al., 2022; Imran, et al., 2021; Jacob, et al, 2021; Albrecht, Jungnicke & von Jan, 2015). For this paper we focus on technological advances that in recent years have made it possible to adapt devices and methodologies for different populations, allowing a better understanding of the cognitive processes mediated by hearing, but not since an assistance idea or to facilitate communication between deaf and hearing people. On the other hand, the design of technological tools where there is an outstanding commitment to the interaction with digital environments promotes better behavior and motivation in users, giving an advantage to the evaluation processes to be more dynamic compared to other traditional ones. This review is divided into three parts. The first part shows a brief description of the executive and cognitive functions; in part two we will give an account of the use of technologies such as interfaces and biometric devices, and the development or adaptation of software for the assessment of these functions. Finally, we conclude with a summary and perspectives on future applications and considerations for developing or adapting technological devices that complement the assessment of executive functions in the deaf population. We introduce a qualitative literature review to explore if there are technological devices that evaluate executive functions or at least one of them, to show alternatives or complement neuroimages techniques or neuropsychological batteries, especially for the difficulties explained before the communication barrier. For this review, we exclude assistance or teaching devices, because the goal was not to evaluate this competence or the design adaptation for physical or communication nor aid hearing. The cochlear implant variable or another hearing aid did also not include because is documented that the cognitive process is usually different in people with hearing aid (van Wieringen et al., 2019; Hua, et al., 2017). Search strategy and selection criteria We searched PubMed and Web of Science, with terms like "deaf", "hearing loss", "hard hearing", "technology devices", "executive functions", and "cognition assessment". Terms excluded "aid hearing", "cochlear implant", "assistance device", "therapy", "education", and "rehabilitation", for reports published between January 2011 to November 2022. Our main focus was on studies that assessed one or more executive functions or cognitive skills through biomedical devices or using technology but not neuroimaging, in deaf people. This was an example of a formula used in research: deaf people AND cognition AND technology NOT hearing aid NOT cochlear implant NOT education NOT therapy We do not include articles published in languages other than English, either type paper-like reviews, conferences, and not available in full text. We decided in this way because most of the research or interventions are focused on teaching sign language or another linguistic topic as well as restoration or hearing assistance. 1. Cognitive and executive functions The construct of executive and cognitive functions has been coined from different perspectives over time. Lezak (1982) distinguished both based on what was intended to be known for each function. To describe cognitive functions, the author emphasized how much knowledge or skills the person possessed; for example, what skills remained intact or were impaired in people, or how well they performed a task compared to another, and on the other hand, executive functions are related to whether people do something or not, i.e., they focus on execution and what is related to it. Barkley (2012) contributes to this meaning by indicating that executive functioning underlies how a person achieves a goal efficiently. Lezak (1982) indicates that we should ask ourselves: ask how well the patient maintains a performance rate, how consistently and effectively he self-corrects, and how responsive to changes in the demands of the task, for example. Recently, executive functions (EFs) have been described as a series of mental processes necessary to be attentive, solve problems, reason, have self-control, and persist in a task (Blankenship et al., 2019; Kral et al., 2016). According to some authors, EFs are framed in three central components, and, from them, other dimensions are derived that are supported by the first ones: working memory, inhibitory control, and cognitive flexibility (Diamond, 2020; Diamond, 2013), Cristofori, Cohen-Zimerman & Grafman, (2019) also include planning, reasoning and problem-solving. For this review, we consider the three central components and the subparts or dimensions associated with each of them, especially attention, which is framed within inhibitory control and seems to be the most studied and controversial function in deaf people. Inhibitory control is required to control behaviors, thoughts, and emotions, and to adapt actions to emit or not a response. It is therefore strongly linked to cognitive control and working memory (Cristofori et al., 2019). This ability supports attention because it is necessary to inhibit external and internal factors and sustain attention to achieve specific goals. Attention is understood as the ability to filter, select, and focus on various elements of the environment (Dye, Hauser & Bavelier, 2008). To this effect, Hauser, Lukomski & Hillman (2008) indicate that inhibition is one of the major cognitive skills because it models motor and behavioral control. It has recently been theorized that inhibitory control is not a single unit, but is composed of a series of functions, among which two main ones are differentiated, response inhibition, which refers to the ability to control impulsive behavior to prevent (inhibit) motor and verbal responses, and interference suppression that involves working memory and refers to the ability to suppress interfering information (Daza Gonzalez et al., 2021). Working memory (WM) involves the ability to retain information in the short term, even when it is not perceptually present, as well as the ability to manipulate that information before it passes into long-term memory (Diamond, 2020; Baddeley, 2017). Two types of WM are generally distinguished, visuospatial and verbal. WM is critical for making sense of anything that unfolds over time, for that always requires holding in mind what happened earlier and relating that to what comes later (Diamond, 2013). The reasoning is closely linked to WM because you need to have the information online long enough to be able to manipulate it and act accordingly. Lastly, cognitive flexibility is built on WM and inhibitory control and is defined as the ability to adapt in the face of environmental change and to generate new ideas that drive innovation and promote growth and discovery (Cristofori et al., 2019; Badre and Wagner, 2006). Cognitive flexibility is associated with an ability to adapt to changing conditions in the environment, which is why it requires control and manipulation of information to know new strategies. Some researchers have been exposed to differences in EFs in deaf people, in particular in attention skills (Zeni et al., 2020; Thakur et al., 2019; Tharpe et al., 2008; Hauser et al., 2007; Bavelier et al., 2000b); the execution of tasks of working memory (Mason et al., 2021; Cardin et al., 2018; Lopez-Crespo et al., 2012; Burkholder & Pisoni, 2003; Pisoni & Cleary, 2003), and inhibitory control (Mason et al., 2021). It seems to be that some executive skills are so close to the linguistic domain that are delayed consolidating (Figueras et al., 2008), maybe because deaf people acquire a late sign language, opposite to oral language that is developed since birth. Often, deaf children do not have access to a language at birth due to the majority being born in a hearing family or because the educational system does not give them an effective early intervention in sign language (Krebs et al., 2021). Thus, the sociocultural context also seems to affect the development and consolidation of some EFs, especially when a deaf child is born into a hearing family environment. On the other hand, EFs seem to be linked with the fact that, when there is sensorial deprivation, the remaining senses appear to be more accurate, which is consistent with the Sensorial Compensation Hypothesis (Pavani & Bottari, 2012). Whereas where in the case of deafness, vision, and tactile sense are more sensitive to inputs from the environment. From the neurocognitive perspective, this is due to the brain's ability to reorganize connectivity to other areas that are not affected by the sensory loss, in this case, there is a major recruitment of visual and tactile areas, although this process of neuroplasticity depends on variables such as the environment, age of onset of deafness and even interindividual factors that influence brain adaptation to sensory loss (Kral et al., 2016). The authors emphasize the possibility that, as the brain is a dynamic system that bases its development on experiences between neural activity and stimulation from the environment, a sensory loss could affect, positively or negatively, domains beyond hearing. This could be concordant with an enhancement in attention skills, for example. The case of disturbance in inhibitory control and working memory seems to be based on hearing feedback, which is coincident with Auditory Scaffolding proposed by (Conway et al., 2009) where some cognitive domains are underlying in sound perception, especially that based on temporally and sequential processing, like working memory. 2. Use of technology to assess cognitive domains in Deaf people One of the most common methods to assess EFs is through neuropsychological tools. However, in the case of deaf people, there are two main factors to take into consideration: first, the communication barrier, since most of the batteries are designed for hearing people, and second, the consideration of the delay in language acquisition as a risk factor for the consolidation of cognitive functions. A systematic review by Vazquez Mosquera (2021) indicated that there are no rigorous instruments with special adaptations to assess deaf children, in this case. This could be a reason that some authors combine technology and assessment cognitive functions. We found design research for deaf children, named AWARD Neuropsychological battery, developed by Gonzalez et al., (2011) that explores cognitive areas from tasks executed in a web application, where they can configure the language depending on user preference, for their research, could be Lengua de Signos Espanola (LSE) or oral language. This software tool allows making a cognitive profile of deaf children by implementing a battery of neuropsychological tests using adaptive web technology, whose main utility would be that professionals in neuropsychology can make use of this tool to minimize communication barriers. It should be noted that, although technological devices are accurate in detecting and evaluating cognitive functions, the design of tasks/paradigms should be more sensitive to detect changes in what is to be evaluated, considering that no brain function occurs in isolation, but rather the sum of interactions of various processes. Based on the literature consulted for this review and taking into consideration that the exploration of EFs in deaf people is less explored compared to studies conducted on hearing people, the studies found so far in this review are described. The sections are divided according to the classification of assessment tools used by the authors of the studies. However, we know that each one had a different population of studies, in terms of adults and children, so we try to limit them to deaf people without cochlear implants, although we emphasize that we cannot generalize the results to the entire deaf population, since the heterogeneity of people must be considered. Within the literature review, we found a wide variety of technological devices that can be used to assess EFs, without most of them being necessarily designed for the deaf population, but rather have been adapted from traditional use in research in other populations and where the paradigms have been adapted by interpreting the instructions into some sign language, for example. That is the reason why the studies shown in this review include technological developments that can be classified as biometric devices, physical and digital interfaces, and video games. This review is an attempt to link the use of technological devices to assess these functions and to give a prospective scenario for future developments and applications. The papers reviewed are in Table 1. Table 1 List of reviewed articles since 2011 to 2022. YEAR TYPE OF COGNITION TYPE OF TECHNOLOGY REFERENCE 2011 Visual attention Eye tracker (Watanabe et al., 2011) 2012 Working Memory Software/interface (Lopez-Crespo et al., 2012) 2013 Visual perception Software/interface (Barca et al., 2013) 2014 Attention and cognitive control Software/interface (Dye & Hauser, 2014) 2015 Visual Attention Eye tracker (Heimler, van Zoest, Baruffaldi, Rinaldi, et al., 2015a) 2015 Visual Attention Eye tracker (Heimler, van Zoest, Baruffaldi, Donk, et al., 2015b) 2018 Visual Attention Eye tracker (Worster et al., 2018) 2018 ANS/Inhibition and Working Memory Software/Interface (Bull et al., 2018) 2019 Visual attention Software/interface (Thakur et al., 2019) 2020 Computational thinking Software/interface/ vibrotactile device (Cano et al., 2020) 2020 Visual attention Eye tracker (Krejtz et al., 2020) 2020 Visual attention Eye tracker (Zeni et al., 2020b) 2021 Emotional arousal and Workload cognition Eye tracker (Tsou et al., 2021) 2021 Visual attention Eye tracker (Bonmassar et al., 2021) 2021 Inhbitory control Software/interface (Daza Gonzalez et al., 2021) 2022 Visual attention and inhibitory control Software/interface (Dye & Terhune-Cotter, 2022) Note: The table shows the type of cognition evaluated in each research and the technological device used for them. 2.1 Biometric assessment: Eye tracking According to the literature consulted for this review, eye tracking is one of the most widely used tools for the evaluation of processes related to visual function, particularly visual attention. The eye-tracker is a biometric sensor technology for recording eye movement and gaze location. Eye-tracking is the process of determining the point of gaze or the point where the user is looking for a particular visual stimulus (Lim, Mountstephens & Teo, 2020). The data obtained can reveal how participants interact with stimuli on a global or specific level (Carter & Luke, 2020). Gaze is the externally observable indicator of human visual attention that can assess cognitive function and (Zeni et al., 2020) performance (Skaramagkas et al., 2021; Krafka et al., 2016). One of the advantages of using eye-tracking is that, depending on the task presented, eye movements can be voluntarily controlled and evaluated for speed and accuracy. Its use within the cognitive area is because visual orientation relates the oculomotor system to cognitive and neurological processes (Carter and Luke, 2020), so accurate inferences can be made about observable behavior and mental state during the performance of visual tasks through estimates of eye and pupil behavior. There are eye-tracking devices with monocular technology that acquire information from only one eye. Theoretically, this should be sufficient since the movements of one eye mimic those of the other, i.e., the eyes tend to move together in the same direction, so knowing the position of one eye can predict the position of the other eye as well. However, binocular acquisition is usually used because this type of biometric data recording reduces errors in precision and accuracy since the on-screen position of both eyes is averaged. On the other hand, there are eye-tracking systems where infrared sources illuminate the eye while a series of cameras, also infrared, capture its reflection, calculating its relative position concerning the physical world. This is because infrared light is reflected in two parts of the eye, the retina, which helps to calculate the center of the pupil (pupil reflection), and the cornea (corneal reflection) (Brunye et al., 2019). The corneal reflection usually does not change when the eyes move, while the pupil reflection does. 2.1.1 Eye-tracking and cognitive functions It appears that hearing loss may underlie visual abilities that are reflected in processes such as attention, which is defined as the general alert to interact with the environment (Lindsay, 2020); and there is the ability to focus perception on one or a group of stimuli by suppressing those that are irrelevant (Diamond, 2013). According to some authors, deaf people seem to use other visual resources or strategies to appropriate and link with the environment. For example, they tend to fixate gaze on or near the eyes and hearing people prefer to fixate gaze at or near the mouth (Heimler et al., 2015a). The development of visual attention and gaze tracking has been the subject of study in the neuropsychological field because they are closely related to attentional control and social cognition, as it accounts for how visual resources are redistributed to interact with and understand the surrounding world. This is clearly seen in the case of deaf infants of hearing parents, where there is a redistribution of attentional resources by having to focus on several stimuli at once, for example, while the caregivers point to something and name it. Deaf infants have to focus on the caregiver, then on what is pointed to, and then on the caregiver again to appropriate that external element. In the case of hearing infants, they only must see the object while the auditory input is present. This can be considered as a precursor to the consolidation of attentional control, and it refers to perception control to focus the mental resources on specific things, so the attention works at the same time as inhibitory control. Visual attention is understood as the process required to isolate relevant information from non-relevant information within a visual scene (Skaramagkas et al., 2021). Within this visual processing, two main attentional functions are evaluated, overt attention and covert attention. In the former, there is a selective orientation towards an object or spatial situation and the observable response is eye movement directed in some direction. Covert attention involves a change in the focus of attention, but no change in eye position or eye movement. Blair and Ristic (2019) indicate that this type of attention evidence how mental resources are aligned with the target of the response, whereas overt attention recruits oculomotor resources toward that target, manifesting in an observable response. Within these overt and covert attention processes is the research of Bonmassar et al. (2021) who observed that the interaction between both types of attention is different in people with deafness, in particular in spontaneous over-eye movement performance when there are social and non-social central cues. The authors observed that deaf participants were slower to respond compared to hearing participants. Bottari et al., (2012) complement this information by indicating there may be a neuroanatomical and functional reorganization underlying eye control when executing covert attention tasks. Also observed that voluntary and reflexive eye movements were more prominent in deaf compared to hearing people. Zeni et al., (2020) used a context of complex naturalistic scenes, observing that deaf people prioritize objects within the images, which leads to infer that attentional differences may refer to an object and not only to the spatial or peripheral context, as previously described, which is consistent with the work of Heimler et al., (2015b) who observed that deaf people have greater control in gaze shifting when monitoring visual space when they are immersed in a social situation. This may be because they require a balance between maintaining spatial attention on the faces of their interlocutor to ensure better communicative and social quality and effective monitoring of the environment. The authors especially emphasize that this control may depend on the experience of acquiring sign language, which makes sense given that it is framed as a visuospatial system that unfolds in a signed space. Given the above, it is important to highlight the design of paradigms for the study of attentional processes. The aforementioned studies used complex contexts which although they are susceptible to involve other cognitive resources, is how it occurs in everyday situations. Another function of attention concerns the allocation of visual resources, which is measured within visual parameters with fixation metrics and saccades. Perhaps one of the goals of recording eye movements can provide information about recognition processes in social situations. For the study of cognition in deaf people, this is of prime importance, because from the knowledge of these parameters it is possible to know the differences between social dynamics when recognizing facial expressions. For example, for the recognition of emotions, there is a greater prominence of visual allocation in the eyes and mouth. Krejtz et al., (2020) examined visual attention while encoding emotions from facial expressions. They found that there was greater accuracy in detecting expressions related to happiness, although there were no significant differences between deaf and hearing. What they did find was a tendency to be faster at recognizing emotional expressions, which they hypothesize may be related to a more prominent reactivity to movement within a peripheral visual field. It was also observed that deaf people directed less attention to the mouth area and more to the eyes. Even a dynamic gaze pattern from ambient to focal was observed, especially during the detection of happiness-related stimuli. In line with these authors, Watanabe et al., (2011) observed that deaf participants also had higher fixation times in the eye and nose area in emotion recognition tasks, confirming that eye contact is a crucial component in processes related to emotions, social skills, and world appropriation. It is interesting to take up again the differences in the allocation of attention between adults and children. As mentioned, deaf adults seem to spend more time looking at their interlocutors, while children interpret social situations by allocating their visual resources, first and for a shorter time, to the person's face and then to the person's body, i.e., they divide their attention to process emotions more effectively within a social context (Tsou et al., 2021). This is consistent with the arguments of Corina & Singleton, (2009) who state that deaf children of hearing parents have a disadvantage in consolidating their attentional process, because not having auditory input, they necessarily must divide their attention between their caregivers and the outside world, i.e., the perceptual and cognitive challenge is greater compared to a hearing child, as mentioned above. However, Worster et al., (2018) observed no differences between deaf and hearing children in speech-reading tasks, so they assume that hearing loss would not necessarily affect gaze behavior. In agreement with the studies of Heimler, et al., (2015a) and Watanabe et al., (2011), Worster et al., (2018) observed that gaze patterns were like those of adults, alternating between eye-mouth-eye gaze. This reinforces the argument that, for deaf people, visual expression contains more socially relevant information compared to other facial elements. As can be observed, the use of biometric tools such as eye trackers to measure functions like visual attention seems to be the most used technology, and perhaps under the assumption that deaf people use other visual mechanisms which may be mediated by several factors such as the acquisition of a sign language, a neuroplasticity effect due to sensory deprivation and even the sociocultural context in which they develop. However, a limitation that arises is the possibility that, as people know that their eyes are being monitored, this may lead to a different behavior in eye tracking, given that the use of eye trackers may affect, in an unconscious way, the movement of the eyes, which would lead to other types of information (Bonmassar, et al., 2021). On the other hand, mapping these visual strategies from eye-tracking allows us to elucidate the visual function underlying other functions, e.g., social skills or another related to reading and writing. 2.2 Digital and Physical Interfaces For this review we found other types of developments that are usually used in research, and that have been adapted for other populations. In this section, we include the interface can be defined as any medium, whether physical or virtual, that allows the interaction between a subject and a machine (Perez-Ariza & Santis-Chaves, 2016). The area that specialized in the development of interfaces is called Interaction Design. Norman (2013) defines it as the branch of design that focuses on understanding the nature of the interaction between people and technologies. The development of technological tools has provided multiple possibilities to evaluate the interactions and behaviors of individuals in front of interfaces to improve them, causing an enhancement in the user experience. For this, software and hardware designs must comply with the usability components, both in the functional development of the system itself and in how people interact with it. Within the classification of interfaces are haptic interfaces, described as devices that allow interaction/communication between person and machine through touch, which may or may not be accompanied by auditory or visual stimuli. Their main characteristic is that they are activated in response to the user's motor action (Hayward et al., 2004). Haptic interfaces are categorized as mechatronic devices because they take advantage of mechanical signals for this exchange of communication between people and machines (Hayward et al., 2004). Among the simplest haptic interfaces are keyboards, buttons, and others more sophisticated such as gloves and exoskeletons. The following are elaborated from a categorization of the digital and physical interfaces found for this review. We describe the use of software and interfaces adapted for the assessment of the specific domains of attention and working memory, followed by using games as an assessment tool. 2.2.1 Digital and Physical Interfaces and EFs Dye and Hauser (2009) used the Gordon Diagnostic System, a portable microprocessor-based continuous performance test that assesses inattention and impulsivity-based behaviors (Foster, 2011). Although the GDS was initially developed to assess children and adolescents with ADHD, the literature reports that children with hearing loss have difficulties maintaining attention and cognitive control (Mason et al., 2021). One of the characteristics of the GDS is that it evaluates through Continuous Performance Tasks (CPT), defined as streams of stimuli that change continuously, and where randomized objective stimuli appear. Participants then must respond to this specific stimulus (Roebuck et al., 2016). Dye and Hauser (2009) evaluated sustained attention, selective attention, and cognitive control, and found that deaf children have a lower performance in the execution of attention and cognitive control tasks, perhaps contingent on the late acquisition of a sign language, so they suggest extending their research to deaf children of deaf parents because in this way it is inferred that they are exposed to a natural language from birth, since in a Deaf family a sign language is the natural language for communication, in the same way that a hearing family communicates orally. A relevant finding in this study was that the participating children were profoundly deaf and had access to a sign language since their deaf parents, and in the results no significant differences were observed between hearing and deaf children, suggesting that hearing deprivation is not sufficient to find significant differences in reported outcomes on attention, as mentioned above. Dye and Terhune-Cotter (2022) conducted a 3-year cohort of deaf children to determine whether there were changes over time in sustained selective attention processes or inhibitory responding and whether these changes were influenced by language and/or deafness. On this occasion, the authors found a significant correlation, observing that learning English is more closely related to better selective attention processing, while the acquisition of American Sign Language (ASL) is more closely related to better inhibitory control. They speculate that the above is due to two factors: the temporal precedes the acquisition process. It is emphasized that ASL is learned through natural exposure to meaningful communicative interactions, i.e., it is an acquisition process. While for English this does not occur, it is learned through therapies and generally after critical periods of neurodevelopment. This seems to be associated with the fact that acquisition occurs spontaneously and unconsciously within a natural context of language use (Krashen, 1982), and on the other hand, the process of learning a language is characterized by a conscious knowledge of rules and their use, which is not reflected in a fluent production of it. Dye and Terhune-Cotter conclude that there is a close relationship between language and cognitive skills, especially in selective attention and inhibitory responding. In this research, the authors indicate that they used a version of the Gordon Diagnostic, the vigilance form, and recommend that they use other types of experimental approaches, which agrees with the findings of the study by Foster (2011) it also recommended that to validate the results obtained from the GDS, it should be combined with other assessment resources. One of the functions that seem to be most compromised in deaf children is working memory (WM). As mentioned, it is a type of short-term memory whose goal is to be able to retain and manipulate information for a short time before it disappears, and which, according to Baddeley's Working Memory Model, is determined by two subsystems based on sensory modalities: 1) the phonological loop, underlying the auditory system, and 2) the visuospatial sketchpad, modulated by the visual and spatial system. It seems to be expected that deaf people have better strategies to perform visuospatial tasks, based on two main assumptions: 1) the enhanced hypothesis or sensory compensation hypothesis, which explains that in people where there is a loss of some sense, other sensory modalities are increased to compensate for the one that is compromised, in the case of deaf people, it would be expected that the visual system incorporates greater resources that would allow greater interaction with the environment, perhaps because the acquisition and use of a visuospatial gestural language that develops within a sign space. Lopez-Crespo et al., (2012) used a computerized version of a DMTS task for visual WM assessment to estimate whether different modes of communication (sign language, oral, or both) determined whether the resources to execute visual WM tasks were different compared to hearing children. Contrary to expectations, deaf children performed less than hearing children, even when the tasks were spatially based. This does not imply, as mentioned by the authors, that there is a delay in WM but perhaps there is another type of functional processing. This study makes it relevant to establish within the methodology the communication mode as one of the variables to have reliable results, i.e. sign language, oral, or both. Recently, Daza Gonzalez et al., (2021) assessed inhibitory control ability using a computerized Stroop task and a short version of the Attention Network Test for children. This research aimed to observe whether the frequency of inattention, impulsivity, and hyperactivity behaviors, as well as disruptive, aggressive, and antisocial behaviors, was higher in a deaf group than in a matched hearing group. And the second aim was to determine whether any behavioral differences between deaf and hearing children could be explained by deficits in inhibitory control. This is due to the idea that deaf children present greater behaviors related to inattention and impulsivity and that this can represent cognitive and emotional difficulties; however, Daza Gonzalez's research showed no significant differences between deaf and hearing children in terms of inhibitory control tasks. The conclusion reached by the authors is that the behaviors presented by deaf children are adaptive visual coding strategies to obtain information from their environment. These visual strategies require redistributing their attentional resources to their central visual field but also to the periphery, which requires a shift of attention to the environment more frequently than hearing people, which may be perceived by others as inattention or hyperactivity (Daza Gonzalez, et al, 2021). From the manipulation of information in a short period and from the apprehension of abstract concepts other functions are also consolidated, for example, the approximate number system (ANS), which refers to a cognitive process where estimates of magnitude are made from abstract representations. This requires other general domains, such as working memory and inhibition, for example, Cai et al., (2018) and Bull et al., (2018) assessed ANS using Superlab 4.0 software and a button-press interaction interface. In the end, it was observed that a deficit in general domains leads to lower performance in ANS task execution, which was more evident in deaf children compared to hearing children, perhaps one of the reasons for this result is that ANS requires several skills such as WM, which involves retention of spatial and temporal information, as well as the allocation of selective visual resources and inhibitory control. The authors indicate that having a lower mastery of these skills impacts lower performance in ANS. As can be seen, devices based on simple physical interfaces, such as a button or a keyboard, are the most common for evaluating tasks in children, maybe because the interaction with the device is so simple. The development of technological tools has provided multiple possibilities to evaluate the interactions and behaviors of individuals in front of interfaces to improve them, causing an enhancement in the user experience. For this, software and hardware designs must comply with the usability components, both in the functional development of the system itself and in how people interact with it. Usability measures the ease of interaction between the user and the interface (Chanchi, 2019) and is based on a set of attributes described by Nielsen (2013): useful, learnable, memorable, effective, efficient, and desirable for the user. In this sense, one growing field in research that meets the above criteria is games, described in the following section. 2.3 Games as tool assessment (Gamification) Another way to evaluate is through the incorporation of games, especially when the population is children. One of the terms in trend is gamification, which refers to the use of games within a ludic context in which participants engage with the cognitive tasks presented, due to the combination of intrinsic and extrinsic motivation; and by integrating challenges and positive feedback, the need for competition is satisfied (Khaleghi et al., 2021). To interact with the environment, processing is required where multisensory interactions are shaped at neural, behavioral, and perceptual levels (Murray et al., 2016). Technology-based games can be used as a vehicle to assess cognitive skills or competencies involved in the game, but not to assess the game (Bellotti et al., 2013). The same authors indicate another category is the so-called serious games focused on being educational, but at the same time, fun/attractive. A review made by the authors mentions that the use of computational games is effective in some therapeutic fields and is related to the development of emotional, cognitive, and perceptual skills. A term that integrates these skills is Computational Thinking, which includes cognitive skills based on a constructionist approach, i.e. users build their knowledge from the understanding of their context (Cano et al., 2020). The use of digital strategies provides the opportunity to interact in different contexts, addressing and building new possibilities of mental processes (Ferreira, et al., 2021) that go hand in hand with a series of steps that give certainty to solving problems. A game designed and developed for deaf children was based on a methodology of the same authors, called MECONESIS (Acronym in Spanish, MEtodologia para CONcepcion de juEgos Serios para nInos con discapacidad auditiva) (Cano et al., 2020). The game simulates a real environment with interfaces and physical elements simultaneously. They also made use of a vibrotactile and visual board, both generated simultaneously. The digital interface was a mobile application, where the children interacted through a QR code and where were instructed on the steps to follow. According to the authors, one of the challenges for the child's development and engagement with the game was the interaction between the physical and digital devices. The authors' work falls into two of the categories we propose for this review. One is the use of digital interfaces, and the other is the vibrotactile board that gives feedback to users as part of the developed game. The combined use of games with other types of devices can be a viable option for the design of cognitive function assessment prototypes, considering the advantages that this offers. Khaleghi et al., (2021) even offer a framework to guide the gamification design process for the assessment of cognitive tasks. This can be a first approach for future research in the Deaf population, where the steps they propose are contemplated and with the background that has already been presented in this review. 3. Discussion Interest in research on cognition in deaf people has been increasing in recent years, not only from the perspective of assistive, recognition, or educational devices but also for research and educational purposes. The evaluation of cognitive processes in deaf people allows inferences to be made from different perspectives: From cognition. From the evaluation of different domains, it is possible to have deep knowledge about the differences in cognitive processes derived from hearing, which would be framed within the Cognitive Hearing Science proposed by Arlinger et al., (2009) that is aligned with an interdisciplinary approach between cognition and hearing. Maybe, although it may seem contradictory, from this field it is possible to rethink and rephrase approaches and research aimed at deaf people. One of the limitations present in the reviewed articles is the heterogeneity of the population even between children and adults. The different etiologies and thresholds of hearing loss do not allow generalizations of the results to establish precise approximations about the development of executive functions. Although deafness is a risk factor for the development and consolidation of these functions, there is no consensus on whether deafness per se affects cognitive functioning or whether it is derived from the socio-cultural context, influenced by a lower interaction with the environment due to communication barriers; it has even been reported that deaf people have lower prosocial behaviors compared to their hearing peers. This is also mentioned by Hauser, Lukomski & Hillman (2008), who argue that in most studies with deaf people, there is no care to select participants and that they are truly representative of the deaf community, so variables such as the age of acquisition of a sign language, socio-cultural context or etiology of deafness should be considered. The evidence shows that there are differences between deaf and hearing people and that these differences do not imply disadvantages or negative issues for cognition in deaf people but seem to exhibit other types of strategies for the appropriation of the world, such as attentional or visual resources, like Daza Gonzalez et al., (2021) proposed in their research. In this sense, we agree with the reflection of Marschark & Hauser (2008) that there is a misconception about the cognition of deaf people and what it is to be Deaf, which leads to a series of barriers in different areas such as work, school, social and even family. One of the EFs that seems to have the greatest difficulty in consolidation is working memory, especially in deaf children. Understanding that differences in this function may underlie learning in mathematics, reading, coordination in motor skills, abstract concept formation, and categorization should be basic to better academic achievement, for example. Auditory experience provides temporal patterns that help develop the above skills, so it would be expected that Deaf children would show difficulties in consolidating areas related to sequential processing, but this is not general for all people. On the other hand, several authors describe advantages in visual processes, particularly those referred to as peripheral visual attention, with emphasis on people who have already acquired sign language, perhaps because visuospatial languages develop in space. However, this visual advantage may entail difficulty in deaf children, because, not having developed inhibitory control, it is common for them to be labeled as distractible or inattentive, although the cognitive basis indicates otherwise. It is imperative to note that one of the variables that stands out as a differentiator in the development of EFs is the early acquisition of sign language. In different contexts, it is known that children are the first generation of deaf people in their hearing family, which hinders the acquisition of a mother tongue in the first years of life, and it is not until a later age that children can have access to sign language. It is worth noting that at this point we would no longer speak strictly of language acquisition, which would occur spontaneously in a natural context (Krashen, 1982), but of language learning, where there is an express search for the linguistic forms to be used and which will allow access to communication resources (Muntzel, 1995). Understanding the basis of the cognitive dimensions in the deaf population allows them to rethink conceptions about their abilities, to design educational strategies that enhance the advantages and help those domains with greater difficulty, and although it is emphasized that neither the results nor the inferences are generalizable to the entire deaf population, it can be a starting point for lines of research and action. From technology. The use of digital devices seems to be increasing for the evaluation of different cognitive processes. In this sense, and within the biometric data devices, the use of eye trackers seems to be the most usual, based on the premise that deaf people have different visual strategies than hearing people, due to the expanded use of space by the form of visuospatial communication. This, however, seems to be mediated by the consolidation of a communicative system, so in people who have not consolidated one, there seem to be differences in the results. This should be considered in the methodological conception to obtain the greatest homogeneity even when there is variability in the participants. One of the advantages of using technological devices to assess EFs is that they can provide more precise information about domains that may not be so evident in a traditional observation. This does not imply that assessment methods such as neuropsychological batteries should be replaced, but perhaps they can be complemented with other types of data that provide additional information for a better understanding of cognition. On the other hand, several authors refer to the use of a single sensory modality for the design of paradigms, so that integrating other sensory resources can provide more information about the processing of different cognitive functions. The current use of gamification seems to open possibilities of conjunction between learning and evaluation through a sense of playfulness, which brings other challenges in usability. As a future scope, the next revision could integrate virtual reality applications. The development of technologies has been increasing and has diversified towards different needs of the deaf population. On the one hand, as teaching tools, to eliminate communication barriers by designing recognition devices or interfaces; others as assistive technologies based on electronic devices such as hearing aids or amplifiers, and the ones we focus on in this review, designs focused on the assessment of cognitive skills. Conclusion The diversity of the use and adaptations of technologies shows the need to implement this type of device as a means, either complementary or primary, for the evaluation of skills and functions related to cognition and that move away from traditional methodologies. Perhaps a line of research that can provide accurate approximations of the development of executive functions is focused on the study and evaluation of different cognitive strategies and tools that would be mediated by the absence of auditory input. In this sense, assessment through technology offers the opportunity to observe and make estimates about cognitive domains and subdomains in deaf people. Although there is ample evidence of the use of standardized systems, such as the eye tracker, or some interfaces, such as the Gordon System Diagnostic, we identified that there are other devices that have not been validated in large populations, which is a limitation mentioned by the authors themselves. Another observation is that there is evidence that combining devices with other types of technologies, can yield more information on how and in what intensity the functions being evaluated occur (Pop-Jordanova & Pop-Jordanov, 2020). Approaches that integrate these parameters can be used to obtain more accurate, sensitive, and specific cognitive level indices. The development of technologies must then consider the interindividual, etiologies, heterogeneity, and sociocultural contexts in which Deaf people develop, and as a prospective scenario based on the above, consider interdisciplinary and collaborative work with the Deaf community itself to provide real and functional results that converge technological innovation and Cognitive Hearing Science. Ethics and Consent Ethical approval and/or consent was not required for this review. Funding Information This research has been supported by a postdoctoral fellowship from the Consejo Nacional de Ciencia y Tecnologia, CONACyT, Mexico, awarded to Dr. Coral I. Guerrero-Arenas. Competing Interests The authors have no competing interests to declare. 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PMC10000330 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1200 VoR Review Branched and Fenestrated Aortic Endovascular Grafts Atkins Aidan D. 1 Atkins Marvin D. MD [email protected] 2 1 Texas A&M University Department of Biomedical Engineering, College Station, Texas, US 2 Houston Methodist DeBakey Cardiovascular Surgery Associates, Houston, Texas, US CORRESPONDING AUTHOR: Marvin D. Atkins, MD Houston Methodist Cardiovascular Surgery Associates, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 1523 01 1 2023 08 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Endovascular repair of abdominal and descending thoracic aortic aneurysms has become the standard of care due to improvements in morbidity and mortality compared to open surgical repair. Late durability, however, remains an issue because persistent endoleaks can lead to continued aneurysm expansion and eventual rupture, sometimes years following the original repair. Branched, fenestrated, and physician-modified endografts in the thoracic arch and thoracoabdominal aorta have extended the seal zone in order to mitigate the risks of proximal and distal endoleaks. This review summarizes the current state of branched, fenestrated, and physician-modified endografts used in complex aortic pathologies. branched endograft fenestrated endograft physician modified endograft thoracic aortic aneurysm thoracoabdominal aortic aneurysm complex abdominal aortic aneurysm pmcIntroduction Endovascular stent grafts have revolutionized the management of abdominal and thoracic aortic aneurysms since their original descriptions by Parodi in 1990 and Dake in 1992.1,2 Since that time, endovascular aortic aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) have become the first-line treatment options for abdominal and thoracic aneurysm repair due to their many benefits, including decreased blood loss, operative time, length of stay, morbidity, and mortality compared with conventional open surgical repair. Successful EVAR and TEVAR are predicated upon landing the devices in the nonaneurysmal, parallel aorta to create a seal zone both proximally and distally. In up to 40% of patients, endovascular repair is limited by anatomical constraints such as inadequate neck length, aortic angulation, or proximal extension of the aneurysm to include one or more visceral or brachiocephalic vessels. EVAR's primary challenge is a difficult proximal sealing and fixation zone, particularly in patients who have a short or angulated infrarenal aortic neck. Type I endoleaks, due to an unfavorable proximal sealing zone, can have dire consequences in the long-term, such as continuing aortic dilatation in the paravisceral segment of the aorta leading to endograft failure and ultimately rupture. Similar issues also occur in the thoracic aorta, where the proximal or distal extent of the aneurysm do not leave enough normal parallel aorta for sealing. Coverage of aortic branches has been used successfully in the thoracic aorta, with coverage of the left subclavian artery and even the celiac artery owing to the robust collateral circulation around each. Such coverage is not typically feasible in the abdominal aorta. Extending the seal zone to normal paravisceral or supraceliac aorta with incorporation of branch vessels using fenestrations, scallops, or directional branches has been used successfully. A fenestration is a hole in the graft, typically 6 or 8 mm in diameter and reinforced with suture and radiopaque markers, that is custom located corresponding to the patients' anatomy. The fenestration is typically bridged with a covered stent graft, and the proximal end of the bridging stent is flared inside of the main body endograft. Scallops are U-shaped cut-outs in the proximal portion of the endograft to incorporate the most proximal branch vessel, typically the superior mesenteric artery (SMA) or celiac artery. Branches are small sections of graft that are sewn to the main body endograft that are typically downward facing. These side branches allow for increased seal zone combined with the bridging stents; however, they necessitate a more proximal deployment of the main body endograft, increasing the risk for paraplegia. Browne et al. reported the first fenestrated aortic repair in 1999 to treat a juxtarenal aneurysm with a single fenestration for a renal artery.3 Anderson reported the first use of a fenestrated endograft that incorporated both renal arteries and the SMA based upon the Cook Zenith EVAR platform.4 In patients without a seal zone in the infrarenal aorta, custom fenestrated endovascular stent grafts have been available in US-based clinical trials since 2006. These devices were approved for short neck (4-15 mm) abdominal aortic aneurysms with a seal zone created within the visceral segment. Since that time, only the Cook ZFEN Fenestrated endograft has been commercially approved in the US (in 2012). Multiple devices from various manufacturers are currently undergoing clinical trials, with several more on the horizon. Due to the lack of commercially available branched or fenestrated devices, many sites have used physician-modified endografts, where an endograft is deployed on the back table and the grafts are modified with either fenestrations or branches and reloaded back into the delivery sheath for implantation. Another option described in detail is the use of a physician-sponsored investigational device exemption. This program allows US physicians to apply to the FDA for a surgeon-specific clinical trial protocol to test newer endografts and/or physician-modified endografts.5 The current literature suggests that as with EVAR, the morbidity and mortality resulting from a fenestrated or branched endograft procedure is at least comparable in the short term to open surgical repair.4 Most fenestrated grafts, however, have been implanted in those deemed high risk for open repair, so there are no direct comparisons between the two treatment strategies. The long-term durability of such grafts, especially physician-modified endografts, is unknown. Reinterventions for device migration, component separation, or branch vessel stenosis or occlusion are not uncommon. As with EVAR, most patients would still choose a minimally invasive option for aneurysm repair even if it means more frequent surveillance and reintervention. This article provides an update on the current status of branch and fenestrated endografts for use in the abdominal, thoracoabdominal, and thoracic aorta. Physician-Sponsored Investigational Device Exemption Aside from industry sponsored clinical trials, another means of evaluating new endovascular devices or physician-modified devices is a physician-sponsored investigational device exemption (PS-IDE). A PS-IDE allows a device not approved by the FDA to be studied similarly to a clinical trial. With this designation, the physician is both the investigator and the sponsor, assuming a greater responsibility than he or she would in an industry-sponsored IDE. The IDE process includes creating a research study protocol and case reporting forms, and submitting an IDE request to the FDA. A study coordinator and monitor are required to ensure the informed consent process, capture all study data per the protocol, and report adverse event data to the institutional review board (IRB) and the FDA. Yearly study reports to the IRB and FDA are standard, as are data audits and case reporting, since the purpose of the IDE is to capture data similar to a clinical trial. By enrolling patients and capturing data as part of an IDE, the procedures are typically eligible for coverage by Medicare with reimbursement. The process of obtaining a PS-IDE can be daunting, but multiple clinical sites around the US have navigated the process and can offer complex endovascular AAA repair to patients. Several sites have joined together as part of the US Fenestrated and Branched Aortic Research Consortium. Single center reports have shown excellent results compared to open surgical repair with regard to operative mortality, freedom from device-related adverse events, late rupture or migration. The limitation of these reports is typically the small sample size. Ten of the busiest PS-IDE sites, which have obtained a PS-IDE to evaluate various Cook medical devices and physician-modified endografts, have pooled their data to provide the largest dataset of branched/fenestrated procedures in the world. This collaboration aims to answer complex questions regarding the burgeoning field of branch and fenestrated abdominal aortic aneurysm repair. Abdominal Fenestrated Endografts The following sections describe the current branched or fenestrated endovascular devices that are commercially available, on trial in the US, or are part of a current PS-IDE. Physician-modified endografts and parallel grafts (including chimneys, snorkels, and periscopes) are considered elsewhere in this journal. Cook ZFEN Device At the present time, the Cook Zenith ZFEN device is the only commercially approved fenestrated device in the US. In 2001, Anderson and Hartley reported the first use of a 3-vessel fenestrated graft in Australia based on the Cook Zenith platform.6 The Cook Zenith ZFEN device is indicated for juxtarenal AAA with at least a 4-mm infrarenal neck. Since commercial approval, it has been used in patients with little or no aortic neck with reasonable success. The Cook Zenith Fenestrated AAA Endovascular graft was commercially approved by the FDA in 2012 and has been commercially available outside the US since 2002. Since 2019, there have been approximately 8,500 implants of the Cook ZFEN proximal device component in the US. The device is custom built for each individual patient's anatomy. The device typically consists of two fenestrations for the renal arteries and either a fenestration or scallop for the SMA . The turnaround time for construction is between 4 to 6 weeks, precluding its use in urgent or emergent situations. Figure 1 Cook Fenestrated ZFEN device. Courtesy of Cook Medical. Cook Fenestrated ZFEN device In 2019, Cook Medical published their annual clinical update on the ZFEN device.4 This 5-year long-term study consisted of 88 patients, including 67 patients enrolled premarket and 21 enrolled following approval of the device. Freedom from AAA-related mortality at 60 months was 97.5%. There was one death on postoperative day 2 secondary to bowel ischemia and a second death of unclear etiology at 2 years that was conservatively counted as AAA related. No death was related to device failure or aneurysm rupture. Freedom from all-cause mortality was 87.9% at 5 years. There was one rupture in the setting of a type 3 endoleak and component separation (which was salvaged endovascularly) occurring at the 5-year follow-up. There were no conversions to open repair or graft explantations. One patient developed acute renal failure requiring dialysis within 30 days. Three patients developed bowel ischemia, with two resolving following intravenous fluids and antibiotics. The third was the above patient who died on postoperative day 2. Main body device stent fracture occurred in two patients and limb separation in one. Four patients required secondary reinterventions due to stenosis or occlusion of renal artery stent grafts. Aneurysm sac size decreased in 76.3% of patients at 5 years, was stable in 18.4%, and increased in 5.3%. Graft migration (defined as > 5 mm with renal stent compression) occurred in one patient and required reintervention. Three patients experienced type 1 proximal endoleak while two had distal endoleak, and all required reintervention. Six patients had type 2 endoleaks due to sac enlargement requiring intervention via coil embolization. The above results are favorable compared with the open treatment of juxtarenal AAA and in a patient population deemed high risk for open surgical repair. The limiting factor for use of the ZFEN device is unusual patient anatomy such as small renal arteries (< 4 mm in diameter), severe aortic angulation, or unusual spacing between the SMA and the renal vessels precluding construction of the device. As the 5-year ZFEN follow-up would suggest, late reinterventions are not uncommon and highlight the need for lifelong surveillance. Cook P-Branch The Cook p-Branch is an "off-the-shelf" design that incorporates three fenestrations and a scallop for the celiac artery. It is designed for aneurysms that start below the SMA origin . The US pivotal p-Branch study has required an infra-SMA neck length of 15 mm. The p-Branch device is a modular system that is 26 mm by 36 mm in diameter. The primary section has a supraceliac uncovered barbed stent followed by nitinol z-stents with one scallop for the celiac artery, one fixed 8-mm strut-free fenestration for the SMA, and two hinged adaptive renal artery fenestrations. These adaptive conical fenestrations have an outer diameter measuring 15 mm at the level of the aortic graft and 6 mm in diameter distally. The small conical branch allows for greater mobility of the stent due to variation in renal anatomy. There are two available renal configurations, one with the renals at the same level and the other with the left renal 4 mm below the right renal artery. The bridging stent used in the trial was the Atrium icast covered stent. In one single-center IDE study, the p-branch device would be applicable to between 60% and 70% of patients presenting with juxtarenal and suprarenal aneurysms.7,8 Utilizing the strict criteria in the US p-Branch pivotal trial, only a third of patients would meet such strict anatomic criteria. Figure 2 Cook p-Branch device with hinged, adaptive renal fenestration. Courtesy of Cook Medical. Cook p-Branch device with hinged, adaptive renal fenestration Based on the European experience with the p-Branch device, the adaptive fenestrations for the renal arteries have shown decreased target vessel patency during follow-up.9 The mechanism appears to be increased strain on the mating stents when the fenestrations are offset and the fenestration is less stable. The off-the-shelf p-Branch device solves the issue of device availability. The proximal p-Branch component, which has two configurations and five diameters, can be kept on hand in limited numbers. The uniformly designed distal bifurcated body is available in four lengths. The procedure is completed with the standard iliac extension limbs used for an infrarenal Zenith device. Thus, a total of 14 devices in stock will cover most anatomies within the instructions for use and is ideal for urgent or emergent use. The Zenith p-Branch Pivotal Study began enrollment in August 2015 and included 80 patients.10 Having completed enrollment, the 12-month results were recently submitted to the FDA for audit. Publication of the results will occur in 2023; pending a positive outcome, the device should be commercially available between 2023 and 2024. Thoracoabdominal Fenestrated Endografts Gore TAMBE The Gore EXCLUDER Thoracoabdominal Branch Endoprosthesis (TAMBE) device is an off-the-shelf four-branch endograft indicated for the treatment of pararenal and type 4 thoracoabdominal aortic aneurysms (TAAA) . The device is currently being studied in the US and Europe in two independent study arms--the primary using solely the TAMBE device to treat pararenal and type 4 TAAA and the secondary using the TAMBE device in addition to proximal conformable GORE TAG thoracic endograft devices placed proximally for type 1,2, and 3 TAAA. Figure 3 Gore TAMBE thoracoabdominal device. GORE(r) EXCLUDER Thoracoabdominal Branch Endoprosthesis (c) 2023. Gore TAMBE thoracoabdominal device Cambiaghi et al. examined the anatomical feasibility of the Gore TAMBE device on all patients presenting at a single European institution with pararenal and TAAA between 2007 and 2017.11 This included patients undergoing open and endovascular approaches in either elective or emergent settings. The anatomical inclusion/exclusion criteria for the US Pivotal trial were used. In those presenting with pararenal aneurysms and type 4 TAAA, 49% of cases could have been treated with the TAMBE device alone. Access feasibility was 85%, aortic feasibility was 74% and visceral vessel feasibility was 72%. In those presenting with type 1, 2, and 3 TAAA, only 23% of cases could have been treated with the TAMBE device with proximal C Tag extensions. Access feasibility was 79%, aortic feasibility was 48% and visceral vessel feasibility was 63%. The low aortic feasibility rate in type 1, 2, and 3 TAAA was felt to be due to size differences between the thoracic aorta and the visceral segment and lack of a dedicated tapered thoracic component. The Gore TAMBE device involves four down-going branches for the celiac, SMA and renal arteries. Deployment involves placement of a 12F sheath via a left axillary artery cut down. A wire is passed from the left axillary sheath and snared through a 22F sheath via the femoral artery. The wire is externalized and a proprietary multichannel catheter is advanced over the wire. Four .014 wires are advanced through the multichannel catheter at the axillary sheath and externalized and advanced through portals in the TAMBE graft to precannulate the side branches. The multichannel catheter prevents wire wrap when advancing the device. The TAMBE device is then introduced to the paravisceral segment and partially deployed. Each .014 wire is then used with a catheter from above and brought into each branch and used to cannulate the corresponding vessel. This wire is then exchanged for a 0.035 Rosen wire. Once all four branch vessels have been cannulated, the TAMBE device is fully deployed. Branching VBX stents are then brought down through a 7F sheath from above and deployed from the TAMBE branch into the branch vessels. The TAMBE device is ballooned above the branches at the proximal seal zone. A bifurcated bridging piece is then deployed into the TAMBE device and extended down into each Iliac artery with Gore Excluder Iliac Branch Endoprosthesis. As of March 2021, this prospective multicenter nonrandomized study involving 45 sites across the US and Europe had enrolled 106 and 23 patients for the primary and secondary study arms, respectively. The primary study arm is complete, with subjects continuing in follow-up. The trial is currently enrolling in the US and Europe and initial results are forthcoming. The device has received Breakthrough Device designation from the FDA. Cook T-Branch The Cook Zenith t-Branch graft is a single configuration off-the-shelf solution for endovascular repair of TAAAs . The graft comes in one size, 34 mm proximally and 18 mm distally, with four downward branches that are accessed from above via the left subclavian artery. The proximal graft contains barbs for additional device fixation. The graft connects to the celiac, superior mesenteric, and renal arteries by way of self-expanding covered vascular bridging stents. The graft includes four gold radiopaque markers to facilitate fluoroscopic visualization and ensure orientation for deployment.The device is currently involved in three ongoing PS-IDE trials in the US. Figure 4 Cook t-Branch thoracoabdominal device. Courtesy of Cook Medical. Cook t-Branch thoracoabdominal device There is significant worldwide experience with the t-Branch device. Bosiers et al. reported the results from three European centers including 80 patients undergoing endovascular repair of TAAA, with 72% performed electively, 7.8% symptomatic, and 19.5% presenting with a contained rupture.12 The t-Branch device was successfully deployed in 79/80 patients. Although one patient died within 30 days and seven patients (8.8%) after 1 year, none were related to aneurysm rupture or explantation. Medtronic Valiant TAAA The Medtronic Valiant TAAA device is an off-the-shelf treatment for TAAA . The device is designed to deploy proximally in the descending thoracic aorta. The system contains two investigational devices: the thoracic bifurcation and the visceral manifold. The thoracic bifurcation is deployed in the proximal thoracic aorta and provides the proximal seal. The two limbs of the thoracic bifurcation allow for continued aortic flow while deploying the visceral segment. The visceral manifold is deployed within the larger 20-mm limb of the thoracic bifurcation to set the stage for the visceral debranching. Each individual visceral branch is sequentially cannulated from above via a sheath in the left subclavian artery. The branches of the visceral manifold extend to the visceral vessel via covered bridging stents and provide distal seal of the manifold. Figure 5 Medtronic Valiant thoracoabdominal aortic aneurysm device. Used with permission. Medtronic Valiant thoracoabdominal aortic aneurysm device As of October 2019, there were five US sites with PS-IDE trials examining the Medtronic Valiant TAAA device, and it had received Breakthrough Device Designation from the FDA. In 2001, this group reported their analysis of 139 patients who underwent treatment with the Medtronic Valiant thoracoabdominal stent graft system.13 The majority of patients (94.2%) underwent a single procedure rather than staged delivery of the branch grafts. Thirty-day, 1-year, and 2-year all-cause mortality rates were 5.8%, 25.2%, and 32.4%, respectively. Paraplegia was noted in 5 patients (3.6%) with 40.3% of cases in Crawford I-III TAAA. Primary and secondary vessel patency rates were 96.2% and 97.5% for all vessels and 95.4% and 96.9% for renal arteries at a median follow-up of 26.9 months. Acute kidney injury (AKI) was reported in 22 patients (15.8%), with 3 requiring permanent dialysis. Five more patients developed worsening renal function and subsequent dialysis through the 2-year study period. In this high-risk population, the Medtronic Valiant TAAA device was thought to be a reasonable solution. The study highlighted the somewhat significant rates of worsening AKI and need for permanent hemodialysis in this patient population. Cook ZFen The commercially available Cook ZFEN device is only approved for a maximum of three custom fenestrations and only a single wide 10-mm scallop. Depending on the device configuration, one of the stent struts may cross the fenestration openings. This can significantly impair the ability to deploy a bridging stent and require back table modification of the strut. It is estimated that two-thirds of complex juxtarenal and pararenal aneurysms are not covered by the ZFEN design.1,2 The Zenith Fenestrated + Endovascular graft (ZFEN +) is an investigational stent graft in preclinical phase that improves upon the current ZFEN design. ZFEN + device is designed for pararenal and type 4 TAAA with a seal created in the supraceliac aorta. The device allows for up to five small or large reinforced fenestrations and incorporates preloaded catheters to facilitate the procedure. This device design has been available outside the US and in select US centers via PS-IDE protocols. The ZFEN + pivotal trial is a prospective international multicenter nonrandomized clinical study in presubmission phase pending IDE submission to and approval by the FDA. It is expected that the ZFEN + device will be applicable to most patients with complex AAAs. Terumo Aortic Custom Fenestrated Anaconda The Terumo Anaconda EVAR device is currently undergoing phase 2 testing in the US for treatment of infrarenal AAA. The custom fenestrated Anaconda device, based upon the same platform, has been used outside of the US for several years for complex juxtarenal and pararenal AAAs. The device can be constructed with up to four fenestrations for the visceral vessels. Data from a UK multicenter study of the fenestrated Anaconda device in 101 patients showed 97.6% target vessel patency at 1 year.14 At 1 year, 75.8% of patients exhibited aneurysm sac regression and 23.1% showed stable aneurysm sac size. Freedom from reintervention at 1 year was 91%. There are currently two US sites enrolling in PS-IDE trials to examine this graft. Thoracic Branched Endografts Gore Thoracic Branched Endograft Device The Gore Thoracic Branched Endograft (TBE) device is the only commercially approved branched thoracic stent graft available in the US . This was approved in May 2022 for use within the left subclavian artery (ie, zone 2). The TBE device incorporates a single internal retrograde branch for arch vessel perfusion. The 3-year midterm results of the early feasibility trial were recently published, showing favorable patency and durability with low rates of graft related complications.15 This cohort consisted of 40 patients (31 zone 2 and nine in zone 0/1). There were no device migrations, stent fractures or aortic ruptures. Freedom from death at 1 and 3 years was 90% and 84%, respectively. A second arm of the study involves deployment of the side branch in zone 0/1. This involves deployment in either the innominate or left common carotid artery with extra-anatomic bypass of the left common carotid or left subclavian artery. Figure 6 Gore thoracic branch endograft device. GORE thoracic branch endograft (c) 2023. Gore thoracic branch endograft device Results from the US Pivotal trial for the Gore TBE device were recently published and resulted in the device's commercial approval.16 This study involved 34 investigational sites and reported the 1-year results of 84 patients who underwent treatment of descending thoracic aneurysms with graft deployment in zone 2 and a side branch into the left subclavian artery. Technical success was achieved in 92% of patients (77/84). There were no aneurysm-related mortalities at 12 months. There was a single case of paraparesis (which completely resolved by 1 year) and a single case of paraplegia that partially resolved. Three patients experienced a procedure-related stroke. One case of type 3 endoleak required reintervention. The device is also being studied in three other cohorts, namely traumatic transection, dissection, and other lesions (penetrating ulcer, IMH) and published results in those cohorts are pending. Medtronic Valiant Navion LSA Device Medtronic endovascular had previously developed and studied a left subclavian branch device based on its Valiant thoracic stent graft platform. The Mona-LSA stent graft had previously undergone early feasibility testing, and results were published in 2015.17 The device was then changed to include the Navion thoracic stent graft platform, which was recalled by the FDA and taken off the market in February 2021 due to stent graft fractures and endoleak concerns. The future status of the Mona LSA branched thoracic stent graft device is unknown. Terumo Relay Branch Device In 2017, Terumo Aortic launched the early feasibility study of their Relay Branch thoracic graft platform in the US. The Relay Branch system is intended for the treatment of thoracic aortic arch pathologies, including aneurysm, dissection, and intramural hematoma requiring coverage of the innominate and left common carotid arteries. The proximal end of the device is intended to land in zone 0 in the ascending aorta. There is a large cannulation fenestration leading to two antegrade internal tunnels. The right and left common carotid arteries in the neck are accessed to deliver the antegrade branches sequentially into the innominate and left common carotid arteries. Worldwide experience with the dual-branch Relay device has been favorable. Tan et al. reported on multicenter data from Europe in 148 patients who underwent treatment of arch pathology with the Terumo Relay Branch device from 2019 to 2022.18 Technical success was achieved in 99.3% of cases. There was one mortality following the procedure but was not thought to be device or procedure related. Six patients (4.1%) developed a disabling stroke and eight (5.4%) suffered a nondisabling stroke during the 2 year follow-up period. Reintervention was required in 16.3% by 24 months and branch vessel patency was 80% (118/147) at 2 years. This experience highlights the major issue of endovascular therapy in the aortic arch, the risk of branch vessel occlusion and stroke. Cook Arch Branch Cook endovascular has designed an inner branch arch endovascular graft. The custom graft seals in the ascending aorta and has up to three proximal internal sealing stents with active fixation barbs on the most proximal sealing stent. A retrospective multicenter analysis of the first 38 patients treated with this device was published in 2014.19 This early feasibility data included an early learning curve for experienced practitioners who have used the device in this high-risk patient cohort. Thirty-day mortality was 30% in the first 10 patients and 7.1% in the subsequent 28 patients, which confirms the significant learning curve with patient selection and procedural experience. This early feasibility study demonstrated reasonable results for total endovascular arch repair in high-risk patients. Haulon et al. recently reported a systematic review on customized (branched and fenestrated) and noncustomized (parallel graft or surgeon-modified fenestrated TEVAR) device techniques for endovascular repair of the aortic arch.20 Their review of the literature from 2000 to 2022 included 30 studies and 2,135 patients. Pathologies included aortic dissection (48%) and aneurysm (46.9%). Custom designed fenestrated and branched custom devices had a technical success rate of 98.3% and 98.7%, respectively; 30-day mortality was 3.8% and 5.4%, and stroke rates were 12.3% and 11%. During 2-year follow-up, reinterventions were required in approximately 10% of patients. The use of noncustomized device techniques with parallel grafts was associated with a technical success of only 76.4%. Physician-modified fenestrated TEVAR had a technical success rate of 91.6%. Mortality rates in the two noncustom techniques were 4.4% and 2.3%. Stroke rates were 4.3% and 3.5%, respectively. This review concluded that endovascular arch repair was associated with acceptable technical success and 30-day mortality in cohorts of high-risk patients. Cerebrovascular event rates averaged approximately 10% and highlighted the Achilles heel of endovascular arch repair. Physician-Modified Endografts The role of back table thoracic aortic endograft modifications for use in the abdominal aorta, much less the aortic arch, remains largely unclear. The Society for Vascular Surgery (SVS) issued an advisory statement in 2013 regarding physician-modified devices and noted that both local IRB and FDA IDE approvals should be obtained prior to use of a physician-modified endograft device. In centers with a PS-IDE, physician-modified endografts are included in their reporting to the FDA. Current evidence would suggest that the results of physician-modified endografts in both the arch and thoracoabdominal aorta are reasonable in high-risk patients without other options. Such cases should be collected in a PS-IDE, and informed consent is paramount when counseling patients beforehand about the unknowns associated with modifying an endograft. Conclusion Endovascular treatment of complex thoracic, thoracoabdominal, and abdominal pathologies continues to gain popularity as a valuable alternative to open surgery, especially in patients unfit for open repair. Endovascular stent graft repair of complex aortic anatomy appears to match, at least in the short-term, the outcomes of open repair with regard to mortality and morbidity. Issues of perioperative stroke continue to plague complex thoracic arch endovascular repair. Late branch vessel patency is a significant issue in the visceral segment of the aorta, especially with regard to the renal arteries and renal function. Continued improvement in endovascular design and deployment techniques will hopefully help to mitigate the above issues. The future of endovascular therapy in complex aortic disease is still in its early history and will continue to have an increasing role for patients. Key Points Custom fenestrated and branched endografts play an increasing role in the management of complex abdominal and thoracic aortic pathologies. Early results of such technologies show at least similar results in morbidity and mortality compared with open repair, although a direct comparison cannot be made as such technologies are typically applied to patients considered high risk for open repair. Late branch endograft failure, especially in the renal arteries, is a significant issue mandating continued surveillance. Acute periprocedural stroke is the Achilles heel of endovascular intervention in the aortic arch. Competing Interests The authors have no competing interests to declare. 1 Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg. 1991 Nov;5 (6 ):491-9. doi: 10.1007/BF02015271 1837729 2 Dake MD, Miller DC, Semba CP, Mitchell RS, Walker PJ, Liddell RP. Transluminal placement of endovascular stent-grafts for the treatment of descending thoracic aortic aneurysms. N Engl J Med. 1994 Dec 29;331 (26 ):1729-34. doi: 10.1056/NEJM199412293312601 7984192 3 Browne TF, Hartley D, Purchas S, Rosenberg M, Van Schie G, Lawrence-Brown M. A fenestrated covered suprarenal aortic stent. Eur J Vasc Endovasc Surg. 1999 Nov;18 (5 ):445-9. doi: 10.1053/ejvs.1999.0924 10610834 4 CookMedical.com [Internet]. Bloomington, IN: Cook Medical; c2023. Zenith(r) Fenestrated AAA Endovascular Graft - Annual Clinical Update; 2019 (cited 2023 Feb 6]. Available from: 5 Abel D, Farb A. Application of Investigational Device Exemptions regulations to endograft modification. J Vasc Surg. 2013 Mar;57 (3 ):823-5. doi: 10.1016/j.jvs.2012.12.025 23446122 6 Anderson JL, Berce M, Hartley DE. Endoluminal aortic grafting with renal and superior mesenteric artery incorporation by graft fenestration. J Endovasc Ther. 2001 Feb;8 (1 ):3-15. doi: 10.1177/152660280100800102 11220465 7 Mendes BC, Rathore A, Ribeiro MS, Oderich GS. Off-the-shelf fenestrated and branched stent graft designs for abdominal aortic aneurysm repair. Semin Vasc Surg. 2016 Mar;29 (1-2 ):74-83. doi: 10.1053/j.semvascsurg.2016.06.005 27823594 8 Mendes BC, Oderich GS, Macedo TA, et al. Anatomic feasibility of off-the-shelf fenestrated stent grafts to treat juxtarenal and pararenal abdominal aortic aneurysms. J Vasc Surg. 2014 Oct;60 (4 ):839-47; discussion 847-8. doi: 10.1016/j.jvs.2014.04.038 24998837 9 Sveinsson M, Sonesson B, Dias N, Bjorses K, Kristmundsson T, Resch T. Five Year Results of Off the Shelf Fenestrated Endografts for Elective and Emergency Repair of Juxtarenal Abdominal Aortic Aneurysm. Eur J Vasc Endovasc Surg. 2021 Apr;61 (4 ):550-558. doi: 10.1016/j.ejvs.2020.12.012 33455820 10 Kitagawa A, Greenberg RK, Eagleton MJ, Mastracci TM. Zenith p-branch standard fenestrated endovascular graft for juxtarenal abdominal aortic aneurysms. J Vasc Surg. 2013 Aug;58 (2 ):291-300. doi: 10.1016/j.jvs.2012.12.087 23611709 11 Cambiaghi T, Grandi A, Bilman V, Melissano G, Chiesa R, Bertoglio L. Anatomic feasibility of the investigational GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis (TAMBE), off-the-shelf multibranched endograft for the treatment of pararenal and thoracoabdominal aortic aneurysms. J Vasc Surg. 2021 Jan;73 (1 ):22-30. doi: 10.1016/j.jvs.2020.03.056 32360681 12 Bosiers M, Kolbel T, Resch T, Tsilimparis N, Torsello G, Austermann M. Early and midterm results from a postmarket observational study of Zenith t-Branch thoracoabdominal endovascular graft. J Vasc Surg. 2021 Oct;74 (4 ):1081-1089.e3. doi: 10.1016/j.jvs.2021.01.070 33684474 13 Lommen MJ, Vogel JJ, VandenHull A, et al. Incidence of Acute and Chronic Renal Failure Following Branched Endovascular Repair of Complex Aortic Aneurysms. Ann Vasc Surg. 2021 Oct;76:232-243. doi: 10.1016/j.avsg.2021.04.045 14 Colgan FE, Bungay PM, Burfitt N, Hatrick A, Clarke MJ, Davies AH, Jenkins M, Gerrard D, Quarmby JW, Williams R. Operative and 1-Year Outcomes of the Custom-Made Fenestrated Anaconda Aortic Stent Graft-A UK Multicenter Study. Ann Vasc Surg. 2018 Jan;46 :257-264. doi: 10.1016/j.avsg.2017.05.027 28619356 15 Liang NL, Dake MD, Fischbein MP, et al. Midterm Outcomes of Endovascular Repair of Aortic Arch Aneurysms with the Gore Thoracic Branch Endoprosthesis. Eur J Vasc Endovasc Surg. 2022 Dec;64 (6 ):639-645. doi: 10.1016/j.ejvs.2022.08.003 35970335 16 Dake MD, Brinkman WT, Han SM, et al. Outcomes of endovascular repair of aortic aneurysms with the GORE thoracic branch endoprosthesis for left subclavian artery preservation. J Vasc Surg. 2022 Nov;76 (5 ):1141-1149.e3. doi: 10.1016/j.jvs.2022.05.014 35709864 17 Roselli EE, Arko FR 3rd, Thompson MM; Valiant Mona LSA Trial Investigators. Results of the Valiant Mona LSA early feasibility study for descending thoracic aneurysms. J Vasc Surg. 2015 Dec;62 (6 ):1465-71.e3. doi: 10.1016/j.jvs.2015.07.078 26483004 18 Tan SZCP, Surkhi AO, Jubouri M, Bailey DM, Williams IM, Bashir M. Does endovascular duration impact clinical outcomes in aortic arch repair? The RELAYTM branched international stance. Front Cardiovasc Med. 2022 Jul 18;9 :969858. doi: 10.3389/fcvm.2022.969858 35924217 19 Haulon S, Greenberg RK, Spear R, et al. Global experience with an inner branched arch endograft. J Thorac Cardiovasc Surg. 2014 Oct;148 (4 ):1709-16. doi: 10.1016/j.jtcvs.2014.02.072.24685375 20 Nana P, Spanos K, Dakis K, Giannoukas A, Kolbel T, Haulon S. Systematic Review on Customized and Non-customized Device Techniques for the Endovascular Repair of the Aortic Arch. J Endovasc Ther. 2022 Nov 8 :15266028221133701. doi: 10.1177/15266028221133701 |
PMC10000331 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1218 VoR Review Genetically Triggered Thoracic Aortic Disease: Who Should be Tested? Duarte Valeria E. MD, MPH [email protected] 12 Yousefzai Raman MS, OMS-IV 3 Singh Michael N. MD 45 1 Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, US 2 Boston Children's Hospital, Boston, Massachusetts, US 3 A.T. Still University-Kirksville College of Medicine (ATSU-KCOM), Kirksville, Missouri, US 4 Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, US 5 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, US CORRESPONDING AUTHOR: Valeria E. Duarte, MD, MPH Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 2428 10 2 2023 15 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Up to 25% of patients with thoracic aortic disease have an underlying Mendelian pathogenic variant. This is a heterogeneous group of disorders known as heritable thoracic aortic diseases (HTAD). Diagnosing associated pathogenic gene variants and syndromes is critical, as the underlying genetics have an implication in medical management, surveillance, thresholds for surgical intervention, surgical risk, pregnancy risk, and risk of inheritance by the offspring. Recently released 2022 American College of Cardiology/American Heart Association guidelines for the diagnosis and management of aortic diseases provide specific recommendations to identify patients at risk for heritable conditions and who should undergo genetic testing. heritable thoracic aortic diseases (HTAD) thoracic aortic aneurysms (TAD) Marfan syndrome (MFS) genetic testing nonsyndromic HTAD genetic variants pmcIntroduction In one population study, the incidence of thoracic aortic aneurysms was 10.4 per 100,000 person-years, showing a three-fold increase in the rate in 1980 to 1994 compared with 1951. In addition, 51% of the patients with thoracic aortic aneurysm were identified in women, who were considerably older at recognition than men.1 Most patients with thoracic aneurysms are asymptomatic and diagnosed incidentally during chest or cardiac imaging or after they present as life-threatening emergencies with dissection or rupture. Unfortunately, in a significant number of patients, the diagnosis is made after death. The recently released 2022 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the diagnosis and management of aortic disease has specific recommendations for identifying patients at risk for heritable conditions who should undergo genetic testing. For risk assessment, it is critical to obtain a multigenerational family history of thoracic aortic disease (TAD), sudden cardiac deaths, and peripheral and intracranial aneurysms.2 Genetic Etiology of Thoracic Aortic Disease Up to 20% to 25% of patients with TAD have an underlying Mendelian pathogenic variant (Table 1). These conditions are known as heritable thoracic aortic diseases (HTAD), a clinically and genetically heterogeneous group of disorders. Identifying pathogenic genes is essential to identify family members at risk for the disease, guide surveillance and management, and evaluate associated vascular and systemic complications.2,3 Table 1 Pathogenic variants associated with heritable thoracic aortic disease (HTAD). TYPE OF HTAD GENETIC ABNORMALITY Syndromic HTAD Marfan Syndrome FBN1 Loeys-Dietz Syndrome TGFBR1 TGFBR2 SMAD2 SMAD3 TGFB2, TGFB3 Vascular Ehlers-Danlos Syndrome (type IV) COL3A1 Nonsyndromic HTAD ACTA2, MYH11, MYLK, LOX, and PRKG1 From a pathological perspective, patients with HTAD show destructive matrix remodeling with elastin fragmentation, proliferation of vascular smooth muscle cells, and a less prominent inflammatory component without atheroma. Eleven genes are confirmed to cause a highly penetrant risk for HTAD: FBN1, LOX, COL3A1, TGFBR1M, TGFBR2, SMAD3, TGFB2, ACTA2, MYH11, MYLK, and PRKG1.2,3 Moreover, HTAD can be subdivided into syndromic and nonsyndromic.4 Syndromic HTAD is associated with genetic syndromes with multisystem involvement, the most common being Marfan syndrome (MFS), followed by other less frequent connective tissue syndromes including Loeys-Dietz (LDS) and vascular Ehlers-Danlos (EDS). The other group, nonsyndromic, comprises a group of patients with an underlying genetic pathogenic variant (mutation) that affects the aorta and, in some, its branches, but no other systems. In addition, there is a group of patients with a family history of TAD with genetic mutation that have unknown pathologic significance or no mutation has been identified. Notably, among the patients with TAD without a diagnosis of MFS or LDS, up to 20% have a first-degree relative with similar features.5,6 Thoracic aortic aneurysms also are associated with Turner syndrome, bicuspid aortic valve, coarctation of the aorta, and other congenital conditions that exceed the scope of this document. Aortic Disease Associated with Genetic Syndromes Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome are the most recognized genetic syndromes associated with HTAD. Marfan Syndrome Marfan syndrome is a systemic disorder of the connective tissue. It is caused by the mutation in the FBN1 gene inherited in an autosomal dominant fashion. The FBN1 gene encodes brillin-1, a glycoprotein that is a major structural component of the extracellular matrix that supports the connective tissues.7,8 The prevalence of MFS ranges between 1 in 5,000 and 1 in 10 000, without any ethnic or gender bias.9 MFS has high penetrance and variable expression. A quarter of patients diagnosed with MFS are new cases due to sporadic (de novo) mutation and do not have a family history.7 MFS is diagnosed using a clinical score called the systemic score and confirmed with genetic testing. The syndrome involves the cardiovascular system and is manifested by aortic aneurysms, aortic dissection, and mitral valve prolapse. It also affects the eye, causing dislocation of the ocular lens (ectopia lentis), manifested as myopia, and skeletal abnormalities due to the overgrowth of the long bones, such as tall stature and increased arm spam, scoliosis, kyphosis, pectus excavatum, pectus carinatum, hindfoot deformity, malar hypoplasia, and abnormal joint laxity, among others.7 Virtually every patient with MFS will have evidence of aortic disease at some point during their lifetime.10 Patients with MFS usually present with aneurysmal dilation of the aortic root and/or the ascending order, or type dissection. Women with MFS are at increased risk of dissection during pregnancy if the aortic diameter exceeds 4 centimeters.9,10 Loeys-Dietz Syndrome Loeys-Dietz syndrome is caused by pathogenic variants in the transforming growth factor receptor type 1 or 2, TGFBR1 or TGFBR2. It is inherited in an autosomal dominant fashion. Other genes associated with this condition are SMAD2, SMAD3, TGFB2, and TGFB3.11,12,13 In LDS, there is arterial tortuosity of the head and neck vessels, aneurysms, hypertelorism, and bifid uvula.14 Other clinical features include cleft palate, translucent skin, malar hypoplasia, retrognathia, blue sclera, cervical spine abnormalities, joint laxity, and developmental delay. These patients also have pregnancy-related complications, including uterine rupture.13 The vascular disease in these patients is aggressive, with early mortality. Most patients have aortic root aneurysms (98%). In LDS, aortic dissection occurs at smaller diameters than in MFS (less than 5 centimeters).13 Therefore, surgical intervention is recommended at smaller diameters.2 Aneurysms also can develop in other vessels, including the subclavian, renal, superior mesenteric, hepatic, and coronary arteries.13 Vascular Ehlers-Danlos Syndrome (type IV) Vascular-type Ehlers-Danlos or Ehlers-Danlos type 4 is an autosomal dominant disorder caused by a defect in type 3 collagen encoded by the COL3A1 gene.15,16 Clinical features include easy bruising, translucent skin, facial features (thin vermilion of the lips, micrognathia, narrow nose, and prominent eyes), and fragility of the arteries, uterus, and bowel. Most patients present with vascular dissection or rupture, gastrointestinal perforation, or organ rupture. The most common cause of death is arterial dissection or rupture primarily involving the thoracic or abdominal arteries, most frequently in the absence of aneurysms.10,16 Surgical repair is complicated by extreme tissue fragility.17 Pregnancy is associated with high risk of rupture of the uterus and arteries. Nonsyndromic Aortic Disease Approximately 13% to 20% of patients with TAD but without MFS or LDS features have affected first-degree relatives.2,5,6 An inherited pattern for TAD has been identified in 21.5% of non-Marfan patients, with the predominant inheritance pattern being autosomal dominant (76.9%) with varying degrees of penetrance and expressivity.18 The age at presentation is lower compared to the mean age in sporadic cases, but not as young as in MFS (mean ages, 58.2 versus 65.7 versus 27.4 years, respectively).5,18 Genetic Variants Associated with Nonsyndromic HTAD Heterozygous pathogenic variants in single genes are responsible for HTAD in most families.2,18,19 Out of the 11 pathogenic genes for HTAD, the ones associated with the nonsyndromic HTAD are ACTA2, MYH11, MYLK, LOX, and PRKG1.2,3,20 ACTA2, the most frequently mutated gene causing HTAD, is associated with a high risk of presentation with acute aortic dissection.21 It has been reported that missense mutations in ACTA2 are responsible for 14% of inherited ascending TAD and dissections. These mutations interfere with actin filament assembly and are predicted to decrease smooth muscle cells contraction, resulting in aortic tissues with medial degeneration, smooth muscle cell (SMC) hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation.20 Guideline Recommendations for Genetic Testing The 2022 ACC/AHA Aortic Disease Guideline recommends that patients with aortic root and/or ascending aortic aneurysms or aortic dissection and any of the following risk factors for HTAD be referred for genetic testing to identify pathogenic or likely pathogenic variants: syndromic features of MFS, LDS, vascular EDS, TAD presenting at age < 60 years, a family history of TAD or peripheral/intracranial aneurysms in a first or second degree relative, and/or a history of unexplained sudden death at a relatively young age in a second-degree relative.2 Furthermore, in patients with an established pathogenic or likely pathogenic variant in a gene predisposing to HTAD, cascade genetic testing of at-risk relatives is recommended along with aortic imaging. The cascade testing of the offspring should be repeated as carriers of the pathogenic variant are identified. In patients who meet the clinical diagnostic criteria for MFS but do not have ectopia lentis, genetic testing is reasonable to exclude an alternative diagnosis of LDS. Variants of unknown significance have not been confirmed to cause TAD and therefore should not be used to identify which family members are at risk or to guide clinical management.2 Genetic testing should always be accompanied by genetic counseling because results can be challenging to interpret, especially in variants of unclear significance and variable strength of association of specific genes with HTAD or pathogenic variants that behave differently, such as variants in the FBN2 gene.3 In patients with syndromic and nonsyndromic HTAD who are contemplating pregnancy, genetic counseling is recommended. What Genes To Test? A multigene panel comprising all genes known to cause HTAD is the recommended approach to testing. Testing panels include FBN1, LOX, COL3A1, TGFBR1M, TGFBR2, SMAD3, TGFB2, ACTA2, MYH11, MYLK, and PRKG1.2,3 Conclusion Once patients are diagnosed with HTAD, it is essential to identify and refer those at risk for heritable HTAD for genetic testing. Diagnosing associated genetic variants and syndromes is critical because the underlying genetics have an implication in medical management, surveillance, surgical intervention threshold, surgical risk, pregnancy risk, and risk of inheritance by the offspring. A panel that includes all genes known to cause HTAD is essential. Genetic counseling should always accompany genetic testing. Key Points Up 25% of patients with thoracic aortic diseases have an underlying Mendelian pathogenic variant. Identifying pathogenic genes is essential to identify family members at risk for the disease, guide surveillance and management, and evaluate associated vascular and systemic complications. Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome are the most recognized genetic syndromes associated with heritable thoracic aortic diseases (HTAD). ACTA2 is the most frequently mutated gene causing nonsyndromic HTAD. Once an established pathogenic or likely pathogenic variant in a gene predisposing to HTAD is identified, cascade genetic testing of at-risk relatives is recommended. Competing Interests The authors have no competing interests to declare. 1 Clouse WD, Hallett JW Jr, Schaff HV, Gayari MM, Ilstrup DM, Melton LJ 3rd. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA. 1998 Dec 9;280 (22 ):1926-9. doi: 10.1001/jama.280.22.1926 9851478 2 Isselbacher EM, Preventza O, Hamilton Black J 3rd, et al. 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022 Dec 13;146 (24 ):e334-e482. doi: 10.1161/cir.0000000000001106 36322642 3 Renard M, Francis C, Ghosh R, et al. Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. J Am Coll Cardiol. 2018 Aug 7;72 (6 ):605-615. doi: 10.1016/j.jacc.2018.04.089 30071989 4 Lindsay ME, Dietz HC. Lessons on the pathogenesis of aneurysm from heritable conditions. Nature. 2011 May 19;473 (7347 ):308-16. doi: 10.1038/nature10145 21593863 5 Coady MA, Davies RR, Roberts M, et al. Familial patterns of thoracic aortic aneurysms. Arch Surg. 1999 Apr;134 (4 ):361-7. doi: 10.1001/archsurg.134.4.361 10199307 6 Biddinger A, Rocklin M, Coselli J, Milewicz DM. Familial thoracic aortic dilatations and dissections: a case control study. J Vasc Surg. 1997 Mar;25 (3 ):506-11. doi: 10.1016/s0741-5214(97)70261-1 9081132 7 Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021 Sep 2;7 (1 ):64. doi: 10.1038/s41572-021-00298-7 34475413 8 Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 Dec 3;366 (9501 ):1965-76. doi: 10.1016/s0140-6736(05)67789-6 16325700 9 Pearson GD, Devereux R, Loeys B, et al. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders. Circulation. 2008 Aug 12;118 (7 ):785-91. doi: 10.1161/circulationaha.108.783753 18695204 10 Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010 Apr 6;121 (13 ):e266-369. doi: 10.1161/CIR.0b013e3181d4739e 20233780 11 Pannu H, Fadulu VT, Chang J, et al. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation. 2005 Jul 26;112 (4 ):513-20. doi: 10.1161/circulationaha.105.537340 16027248 12 Tran-Fadulu V, Pannu H, Kim DH, et al. Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. J Med Genet. 2009 Sep;46 (9 ):607-13. doi: 10.1136/jmg.2008.062844 19542084 13 GeneReviews [Internet]. Bethesda, MD: National Library of Medicine; c2023. Loeys BL, Dietz HC. Loeys-Dietz Syndrome; 2018 Mar 1 [cited 2023 Feb 10]. Available from: 14 Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006 Aug 24;355 (8 ):788-98. doi: 10.1056/NEJMoa055695 16928994 15 Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175 (1 ):8-26. doi: 10.1002/ajmg.c.31552 28306229 16 GeneReviews [Internet]. Bethesda, MD: National Library of Medicine; c2023. Byers PH. Vascular Ehlers-Danlos Syndrome; 2019 Feb 1 [cited 2023 Feb 10]. Available from: 17 Ascione R, Gomes WJ, Bates M, Shannon JL, Pope FM, Angelini GD. Emergency repair of type A aortic dissection in type IV Ehlers-Danlos syndrome. Cardiovasc Surg. 2000 Jan;8 (1 ):75-8. doi: 10.1016/s0967-2109(99)00070-8 10661708 18 Albornoz G, Coady MA, Roberts M, et al. Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg. 2006 Oct;82 (4 ):1400-5. doi: 10.1016/j.athoracsur.2006.04.098 16996941 19 Milewicz DM, Chen H, Park ES, et al. Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections. Am J Cardiol. 1998 Aug 15;82 (4 ):474-9. doi: 10.1016/s0002-9149(98)00364-6 9723636 20 Guo DC, Pannu H, Tran-Fadulu V, et al. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. 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PMC10000332 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1217 VoR Issue Introduction The Spectrum of Care for Aortic Disease Lumsden Alan B. MD [email protected] 1 1 Methodist DeBakey Heart & Vascular Center, Houston Methodist, Houston, Texas, US CORRESPONDING AUTHOR: Alan B. Lumsden, MD Methodist DeBakey Heart & Vascular Center, Houston Methodist, Houston, Texas, US [email protected] 07 3 2023 2023 19 2 13 08 2 2023 08 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See aortic disease endograft graft explantation abdominal aortic aneurysm Alan B. Lumsden receives research support from W. L. Gore & Associates, CorMatrix Cardiovascular, Silk Road Medical, and Cook Medical. He also consults with Boston Scientific, W. L. Gore & Associates, Siemens, Medical Metrics, Nova Signal, Intact Vascular, Karl Storz, Avail Medsystems, AneuMed, Silk Road Medical, Hemostemix, and KOL BioMedical and is a shareholder in Hatch Medical. pmcAortic diseases have varied pathologies and, increasingly, new options for treatment. The causes of aortic disease may vary from congenital or genetic conditions to infection, traumatic accidents, degenerative or inflammatory disorders. Environmental influences clearly contribute to increased occurrence, with known risk factors including hypertension, aging, smoking, and trauma. While preventive and pharmacological interventions have been explored in recent years, surgery or Endovascular intervention continues as the recommended solution when treating most cases. This issue of the Methodist DeBakey Cardiovascular Journal explores the major types of aortic disease and their various options for treatment and repair. We open with a review of dynamic imaging of aortic pathologies by Drs. Dipan J. Shah, Alan B. Lumsden, Peter Osztrogonacz, and colleagues, who note that today's vascular surgeons can choose from a wide array of imaging modalities to evaluate different aortic pathologies. Despite the fact that newer dynamic imaging techniques provide time-resolved information in various aortic pathologies compared to the standard imaging modalities of vascular ultrasound and aortography, these newer techniques have not seen widespread adoption. To help readers decipher the role of emerging modalities, the authors provide an overview of dynamic imaging techniques for aortic pathologies and describe various dynamic computed tomography and magnetic resonance imaging protocols, clinical applications, and potential future directions. Next, we explore the topic of branched and fenestrated aortic endovascular grafts with Dr. Marvin D. Atkins and coauthor Aidan D. Atkins. Although improvements in morbidity and mortality have made endovascular repair of abdominal and descending thoracic aortic aneurysms the standard of care, late durability is problematic due to persistent endoleaks that may lead to aneurysm expansion and eventual rupture. The authors explore the current state of branched, fenestrated, and physician-modified endografts used in complex aortic pathologies--including early results of such technologies that show at least similar short-term outcomes compared with open repair--as well as issues such as late branch endograft failure and acute periprocedural stroke. From here, Drs. Valeria Duarte, Michael Singh, and Raman Yousefzai discuss the increase in genetically triggered thoracic aortic disease. Up to 25% of patients with thoracic aortic disease have an underlying genetic predisposition, which makes diagnosis critical from both a medical management perspective and to identify at-risk family members. The authors explain the genetic etiology of thoracic aortic disease, identify aortic diseases associated with genetic syndromes, review the recent ACC/AHA guidelines, and discuss specific testing protocols for patients predisposed with heritable thoracic aortic disease. Authors Michael Reardon, Marvin Atkins, and Aidan Atkins then delve into endovascular management of the ascending aorta. Thoracic endovascular aortic stent graft repair (TEVAR) has revolutionized the management of descending aortic pathologies, showing significant improvements in mortality, morbidity, and recovery time. However, devices designed specifically for the ascending aorta are desperately needed for those patients unfit for open surgical repair. The authors update readers on the unique challenges of endovascular management of the ascending aorta and look at the future technologies that will define this space. The dramatic increase in the number of aneurysms treated with abdominal aortic endografts has spurred more interest in graft explantation. Open procedures can be particularly challenging, especially in patients with nonremedial type 1 endoleaks or graft infections. With up to 70% of primary repairs performed with an abdominal aortic endograft, an overwhelming number of explants continue to be performed in the abdomen. In the article titled "Explant of the Aortic Endograft: Today's Solutions, Tomorrow's Problems," I address some of the technical challenges and management of these patients and focus on practical challenges associated with removing these devices. From here, Drs. Anthony Estrera, Akiko Tanaka, and colleagues review open treatments for thoracoabdominal aortic aneurysm repair (TAAA), for which Michael E. DeBakey and colleagues developed a Dacron graft to shunt between the descending thoracic aorta and infrarenal abdominal aorta to minimize visceral and renal ischemia. The current standard practice of TAAA repair includes myriad techniques, such as left heart bypass with mild hypothermia or cardiopulmonary bypass with moderate/deep hypothermia, among others, and the authors explore these techniques in detail. They also explain how their use of distal aortic perfusion and cerebrospinal fluid drainage combined with moderate passive hypothermia has reduced the overall spinal cord ischemia rate after extent I TAAA. Drs. John F. Eidt and Javier Vasquez then shift focus to the changing management of type B aortic dissections (TBAD). Despite contemporary advances in medical and surgical care, acute aortic dissection remains a highly lethal and morbid condition, with almost one-third of patients never reaching the hospital. The authors explore four significant trends in the management of type B aortic dissection, including (1) the adoption of a new classification system that resolves deficiencies of the DeBakey and Stanford systems; (2) recognition that thoracic endovascular aortic repair (TEVAR) fails to effectively prevent aneurysmal degeneration in the untreated aortic segments; (3) increasing use of TEVAR in uncomplicated TBAD despite the absence of definitive proof of efficacy; and (4) the emergence of a variety of techniques and devices designed to improve the long-term outcomes of TBAD. We then step back to look at the medical management of aortic disease. While surgery is the cornerstone of management for most aortic conditions, medical therapy is now an important adjunctive therapy in most if not all aortic patients. A preemptive diagnostic approach with a multidisciplinary team and shared decision-making has led to improved clinical outcomes. Control of blood pressure, cholesterol, lifestyle factors, and comorbidities are all important and meaningful targets to optimize outcomes in aortic disease patients. In their review, Drs. Maan Malahfji and Mujtaba Saeed review the role and evidence behind medical management of patients with aortic disease. Ruptured abdominal aortic aneurysm is an acute aortic condition that requires immediate action and appropriate continuity of care to optimize patient outcomes. A systematic standardized protocol-driven approach is essential to improve the management of aortic emergencies as well as perioperative morbidity, mortality, and long-term survival. In their review, authors Maham Rahimi, Peter J. Osztrogonacz, Vy C. Dang, and colleagues summarize the internal protocol of the Houston Methodist Hospital Acute Aortic Treatment Center to provide guidance to vascular surgeons in training and also to low-volume aortic centers, following the five phases of surgical care outlined by the American College of Surgeons (ACS): preoperative, perioperative, intraoperative, postoperative, and post-discharge. The quality of any cardiovascular program depends in large part on the competency and care of its nursing staff. Having specialty trained and certified cardiovascular nurses has been shown to help decrease delays in cardiac referral and treatment, reduce hospital stays in patients with cardiac disease, and prevent rehospitalization. Against the backdrop of an ongoing nurse shortage, healthcare organizations need strategic plans to support, build, and retain a strong team of CV nurses. Gail M. Vozzella, DNP, RN, NEA-BC, and Michelle C. Hehman, PhD, RN, close this issue describing the numerous forces driving the current nursing shortage and the impact of the coronavirus-19 pandemic on nurse job satisfaction and turnover. They also present a reinvented model of nursing care as a framework for healthcare organizations to address nurse staffing challenges. The articles presented here are shared in the spirit of offering useful insights and approaches for treating aortic diseases and repairing the damage they have caused. To learn more about aortic disease treatment and see additional video clips of aortic procedures, I include links to the extensive video library of DeBakey Cardiovascular Education. More videos, in addition to those shared in the articles included here, can be found on the DeBakey Cardiovascular Education YouTube channel at Guest Editor Biography The editors of the Methodist DeBakey Cardiovascular Journal express our appreciation to Dr. Alan B. Lumsden for his knowledge and insight in developing this issue on aortic disease. Alan B. Lumsden, MD Dr. Lumsden's academic career began in 1989 at Emory University in Atlanta, Georgia, where he completed his postdoctoral training and served as a Collaborative Scientist in the Division of Pathobiology and Immunology at the renowned Yerkes Primate Center. He remained at Emory for several years, rising to the rank of associate professor and chief of the Division of Vascular Surgery. In 2002, Dr. Lumsden joined the faculty at the Baylor College of Medicine in Houston, Texas, as professor and chief of the Division of Vascular Surgery and Endovascular Therapy. He assumed his current positions at Houston Methodist in 2008. Dr. Lumsden has developed an international reputation as a leader in the field of endovascular surgery. He has clinical and research expertise in stent graft treatment of thoracic and abdominal aortic aneurysms, stenting and endarterectomy in carotid arterial disease, renovascular hypertension, aortoiliac occlusive disease, and mesenteric vascular and minimally invasive therapy in venous disease. Dr. Lumsden also conducts FDA-mandated training for surgeons nationwide in a carotid stenting simulator housed at the Houston Methodist DeBakey Heart & Vascular Center. Dr. Lumsden's research interests include developing novel minimally invasive methods of therapy and preventing restenosis. His research has been funded by the National Institutes of Health, and he has contributed more than 200 papers to the medical literature, as well as numerous abstracts, books, and book chapters. Competing Interests Alan B. Lumsden receives research support from W. L. Gore & Associates, CorMatrix Cardiovascular, Silk Road Medical, and Cook Medical. He also consults with Boston Scientific, W. L. Gore & Associates, Siemens, Medical Metrics, Nova Signal, Intact Vascular, Karl Storz, Avail Medsystems, AneuMed, Silk Road Medical, Hemostemix, and KOL BioMedical and is a shareholder in Hatch Medical. |
PMC10000333 | Methodist Debakey Cardiovasc J Methodist Debakey Cardiovasc J 1947-6108 Methodist DeBakey Cardiovascular Journal 1947-6094 1947-6108 Houston Methodist DeBakey Heart & Vascular Center 10.14797/mdcvj.1214 VoR Poet's Pen Old Ironsides Young James B. MD [email protected] 12 1 Emeritus Executive Director of Academic Affairs, Cleveland Clinic and Professor Emeritus of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, US 2 Section Editor, Poet's Pen, Methodist DeBakey Cardiovascular Journal CORRESPONDING AUTHOR: James B. Young, MD Emeritus Executive Director of Academic Affairs, Cleveland Clinic, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, US [email protected] 07 3 2023 2023 19 2 103106 03 2 2023 08 2 2023 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See Dr. Oliver Wendell Holmes Sr. was a 19th century elite physician, curmudgeon, essayist, and poet. His works were numerous, insightful, entertaining, and characteristic of the pre-Civil War, Civil War, and Gilded age eras. Many of his shorter poems are taught in high school as examples of late 19th century works, as they are relatively easy to memorize and understand. Holmes and the Fireside Poets (Emerson, Longfellow, and Lowell, among others) created works that, in their time, were read aloud by fathers and mothers to their family because the poems often centered around values, morals, and historic events. "Old Ironsides" is characteristic of the type of work for which the Fireside Poets became famous. It is an entertaining poem to read, study, and hear, particularly when linking it to the oldest ship in the world, still afloat and sailing around Boston Bay. pmcOld Ironsides Ay, tear her tattered ensign down! Long has it waved on high. And many an eye has danced to see That banner in the sky; Beneath it rung the battle shout, And burst the cannon's roar; -- The meteor of the ocean air Shall sweep the clouds no more! Her deck, once red with heroes' blood Where knelt the vanquished foe, When winds were hurrying o'er the flood And waves were white below, No more shall feel the victor's tread, Or know the conquered knee; -- The harpies of the shore shall pluck The eagle of the sea! O, better that her shattered hulk Should sink beneath the wave; Her thunders shook the mighty deep, And there should be her grave; Nail to the mast her holy flag, Set every thread-bare sail, And give her to the god of storms, -- The lightning and the gale! Oliver Wendell Holmes Sr, MD Uss Constitution as "Old Ironsides" "Old Ironsides"1,2 is an iconic poem written by the physician, curmudgeon, and poet Oliver Wendell Holmes Sr (1804-1894). Holmes Sr should not be confused with his son, Oliver Wendell Holmes Jr (1841-1934), associate justice of the Supreme Court, nicknamed "the Great Dissenter." The poem has been a staple for youthful classes of literature and poetry because of its catchy tone, cadence, and important reference to American history. Its style is old school and short enough to be easily memorized (three eight-line stanzas), with a catchy rhyming pattern as each stanza has its own distinct rhyming scheme.1,2,3 It was written in 1830, on the eve of the warship USS Constitution being decommissioned from the United States Navy, and very early in the career of Holmes as a poet and curmudgeon. The poem was published in the Boston Daily Adviser in response to an article in the New York Journal of Commerce, detailing the fact that the USS Constitution was to be decommissioned and sundered for scrap. This was after an extraordinary history of protecting democracy and the United States of America. Particularly notable was its defense during the War of 1812. Figure 1 USS Constitution port broadside. [Between 1900 and 1920] Photograph. Detroit Publishing Co., Publisher. Retrieved from the Library of Congress, <www.loc.gov/item/2016817278/> USS Constitution port broadside. [Between 1900 and 1920] Photograph. Detroit Publishing Co., Publisher. Retrieved from the Library of Congress, <www.loc.gov/item/2016817278/> This is the first poem in Holmes' poetry compendium after his solicitous introduction to his readers.2 At the beginning of the poem, Holmes seems to take the position of endorsing decommissioning of this glorious warship. The poem suggests that the distinctive ensign, that was flown high, should be torn down and permanently fixed to the ship's mast. The author had other ideas about how to honor the glory of the historic USS Constitution by putting it on display, albeit that "...her shattered hulk/should sink beneath the wave" but only after nailing "to the mast her holy flag" and setting "every thread-bare sail" while giving her to the god of storms. The history of the USS Constitution goes back to the beginning of our republic. She is a three-masted heavy frigate with an impenetrable oak hull (thus the name "Ironsides"), launched in 1797 as part of the Naval Act of 1794. She was the third of six commissioned warships. George Washington himself approved the name "Constitution." She protected merchant shipping during conflicts with France and the First Barbary War. Her actions in the War of 1812 were particularly significant and important, prompting public adoration that saved her from the scrap heap on several occasions. The oldest ship in the world still floating, and intermittently sailing, she currently is on "active duty," moored in Boston Harbor near the Boston Freedom Trail with a Navy crew of around 75 sailors. My attachment to the ship is the name of the Ohio Township, Bainbridge, in which I live. When my wife and I recently toured the USS Constitution, I discovered that Captain William Bainbridge was the frigate's commander during the War of 1812. Several other municipalities, many streets, and a few warships carry the name "Bainbridge" as well. I have yet to come across any neighbors who know the history of our township's name or know much about the War of 1812 and how our Ohio "Western Reserve" got the name and why. Figure 2 Oliver Wendell Holmes Sr, by Jacques Reich, 1899. National Portrait Gallery, Smithsonian Institution; gift of Oswald D. Reich. Oliver Wendell Holmes Sr, by Jacques Reich, 1899. National Portrait Gallery, Smithsonian Institution; gift of Oswald D. Reich Oliver Wendell Holmes Sr studied medicine in Paris at first, then returned to Boston and Harvard School of Medicine, where he received his medicine degree in 1836 after he penned "Old Ironsides."4 He taught at Dartmouth School of Medicine before returning to Boston and Harvard, where he had a long and distinguished career. He championed the unpopular concept of puerperal fever being an infection transmitted by doctor's carrying the scourge from patient to patient via filthy hands, clothing, and instruments. Holmes also was part of a literary group of prominence that included Henry Wadsworth Longfellow, William Cullen Bryant, John Greenleaf Whittier, and James Russell Lowell, collectively known as the Fireside Poets. His works were often published in The Atlantic Monthly, and he continued his literary career throughout his medical career, earning him the label of a literary physician writer (William Carlos Williams was of the same ilk almost a century later). With respect to the profession of medicine, Holmes was a reformer. In addition to his attention to puerperal fever, he focused on the poor hygienic conditions of the Boston Dispensary. He railed against many contemporary practices with the quote, "If all contemporary medicine was tossed into the sea it would be all the better for mankind--and all the worse for the fishes."5 He also demeaned quackeries and homeopathy, labeling the later "the pretended science...mingled with a mass of perverse ingenuity, of tinsel erudition, of imbecile credulity, and of artful misrepresentation, too often mingled in practice."6 Holmes traveled extensively throughout New England, wrote poetry, essays, and novels, saw patients, and at one time was critical of the abolitionists. In the end, he was a passionate supporter of the Union side of the Civil War. Later in life, Holmes slowed as he aged but also traveled to Europe, received numerous honorary degrees, kept up his association with his literary friends, and died peacefully in 1894. He seems better known for his literary adventures than his medical work. Though his poetry and other writings might be labeled stilted and old fashioned, careful reading uncovers his wit and wisdom. Competing Interests The author has no competing interests to declare. 1 PoetryFoundation.org [Internet]. Chicago, IL: Poetry Foundation; c2023. Oliver Wendell Holmes Sr. Old Ironsides; 2023 [cited 2023 Feb 6]. Available from: https/old-ironsides//www.poetryfoundation.org/poems/46547/old-ironsides 2 Holmes OW. The Poetical Works of Oliver Wendell Holmes. Boston, MA: Houghton, Osgood and Co; 1879. 324 p. 3 PoemAnalysis.com [Internet]. London, United Kingdom: Poem Solutions Limited; 2023. Oliver Wendell Holmes; 2023 [cited 2023 Feb 6]. Available from: 4 Hoyt EP. The Improper Bostonian: Dr. Oliver Wendell Holmes. New York, NY: William Morrow & Co; 1979. 319 p. 5 Sullivan W. New England Men of Letters. New York, NY: Atheneum Books/Simon & Schuster; 1972. 256 p. 6 Homeoint.org [Internet]. Sylvain Cazalet, publisher; 2006. Homeopathy and its Kindred Delusions by Dr. Oliver Wendell Holmes; 2023 [cited 2023 Feb 6]. Available from: |
PMC10000334 | Erratum. In the haste of writing, on the first line of page 670, of The Journal, we inadvertently put down Henry instead of Hughes, as every one knows it should have been written. We beg J. Hughes Bennett's pardon. |
PMC10000335 | Glob Heart Glob Heart 2211-8179 Global Heart 2211-8160 2211-8179 Ubiquity Press 10.5334/gh.1165 VoR Abstract Abstracts from the World Congress of Cardiology/Brazilian Congress of Cardiology 2022 The Editorial Team (on behalf of the World Heart Federation)[email protected] 1 1 On behalf of the World Heart Federation, Switzerland CORRESPONDING AUTHOR: The Editorial Team On behalf of the World Heart Federation, Switzerland [email protected] 07 3 2023 2023 18 1 1026 9 2022 26 9 2022 Copyright: (c) 2023 The Author(s) 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See These are the abstracts from the combined 77th Brazilian Congress of Cardiology, together with the World Congress of Cardiology, held in October 2022. From 1950 to today, the World Heart Federation's World Congress of Cardiology (WCC) has been a key event on the cardiovascular calendar, offering a global perspective on cardiovascular health and bringing together thousands of cardiology professionals from all over the world with one common goal: to reduce the global burden of cardiovascular disease and help people live longer, healthier lives. Cardiology Global Health Heart Health Cardiovascular Disease Conference pmc107880 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality in a 3-Year Follow-Up of Congestive Heart Failure Due to Chagas Disease in Women and Men ANTONIO DE PADUA MANSUR1, Carlos Henrique Del Carlo1, Jose Antonio Ramos Neto1, Andre Barbosa de Abreu1, Airton Roberto Scipioni1, Antonio Carlos Pereira Barreto1 (1) Insituto do Coracao - HC FMUSP Background: Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of congestive heart failure (CHF) in Latin America and carries a high morbidity and mortality burden. Previously, it was believed that there was no epidemiological and clinical evidence of a gender-associated risk of death in patients with CCC. Purpose: To analyze the mortality of congestive heart failure due to CCC in women and men. Methods: From February 2017 to September 2020, we followed a cohort of patients with CHF (Framingham criteria) due to CCC in a single-center outpatient clinic. Appropriate serologic tests defined Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed with the Kaplan-Meier (K-M) method to analyze time-to-event data and the Cox proportional hazards methods to search for predictors of death. Results: We studied 733 patients, mean of 61.4 +- 12.3 years, 381 (52%) males. Females were older (63.0 +- 11.9 vs. 60 +- 12.4 years; p = 0.01), had a higher baseline mean left ventricular ejection fraction (LVEF) (44.5 +- 14.6% vs. 37.3 +- 14.8%; p < 0.001), and a lower left ventricular diastolic diameter (LVDD) (56.7 +- 8.9 vs. 62.4 +- 9.4 mm; p < 0.001). Over a 3-years follow-up period, 168 (44%) men and 126 (36%) women died . Women had more implantable pacemakers (PM) (26.1% vs. 16.5%; p = 0.002) and men more implantable cardioverter-defibrillators (ICDs)(20.7% vs. 12.5%; p = 0.003). Heart transplant occurred in 10.8% of men and 7.4% in women (p = NS). Cox regression for death adjusted for age, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation, PM, ICD, heart transplant and LVEF, showed, in descending order, previous stroke (HR = 2.4; 95%CL:1.5-3.6), diabetes (HR = 2.0; 95%CL: 1.3-3.1), and CKD (HR = 1.8; 95%CL:1.3-2.6) as the main predictors of death in men, and in women diabetes (HR = 2.2; 95%CL:1.4-3.4), previous stroke (HR = 1.8; 95%CL:1.1-2.9), and CKD (HR = 1.7; 95%CL:1.1-2.7). Conclusions: Women had a better prognosis than men but similar predictors of death. Control of diabetes and prevention of stroke and CKD could significantly reduce the death rate in CHF due to CCC. 108498 Modality: WHF Abstracts - Young Researcher Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 14/10/2022 H: 16:50/17:50 L: Auditorio 14 Relationship between Sociodemographic Index and Ischemic Heart Disease in Brazil in the Period of 2000-2019 JOSE LUCAS PERES BICHARA1, Jose Lucas Peres Bichara1, Luiz Antonio Viegas de Miranda Bastos1, Paolo Blanco Villela1, Glaucia Moraes de Oliveira1 (1) Universidade Federal do Rio de Janeiro - UFRJ Introduction: Cardiovascular diseases (CVD) are the main causes of death in the world and in Brazil, and ischemic heart diseases (IHD) are one of the main responsible for these statistics. Previous studies have already suggested a relationship between the evolution of IHD mortality rates and socioeconomic indicators. Objective: To relate the evolution of IHD mortality rates and the sociodemographic index (SDI) from 2000 to 2019 in Brazil and in its federative units (FUs). Methods: Ecological time series study of deaths from IHD in Brazil. Crude and standardized mortality rate for IHD were analyzed by sex, age group and FU between 2000 and 2019. Data were correlated with the SDI. Deaths and population were taken from DATASUS to estimate crude and standardized mortality rates per 100,000 inhabitants (direct method with Brazilian population in 2000). The SDI for each UF was extracted from the Global Health Data Exchange website. Results: In the period, there were 1,968,160 deaths from IHD in Brazil, 58.19% of which were male. The national SDI ranged from 0.538 in 2000 to 0.64 in 2019, with constant growth in the period. Concomitantly, the age-standardized mortality rate for IHD decreased from 46.12/100,000 inhabitants to 36.42/100,000 inhabitants. Thus, IHD has become the leading cause of mortality in the country. In the FUs, all states in the North and Northeast regions showed improvements in the SDI, however, the best indicators continued to be concentrated in the other regions. In 2000, the highest mortality rates from IHD were found in the South, Southeast and Midwest regions of the country, but they showed a significant reduction. When evaluating the variation of the standardized mortality rate in the period, it was noted that the FUs with the best SDI were responsible for the greatest drops (graph 1). Conclusion: During the period, the country showed a significant improvement in socioeconomic indicators accompanied by a reduction in IHD mortality rates. When evaluating the FUs, it was noted that those with better socioeconomic indicators were able to obtain a greater reduction in these mortality rates. 108502 Modality: WHF Abstracts - Researcher Category: NEGLECTED CARDIOVASCULAR DISEASES D: 14/10/2022 H: 13:50/14:50 L: Auditorio 14 Association between Autonomic Denervation, Myocardial Hypoperfusion, Fibrosis and Ventricular Arrhythmias in Chagas Cardiomyopathy ADRIANA SOARES XAVIER DE BRITO1, Renata Junqueira Moll-Bernardes1, Martha Valeria Tavares Pinheiro1, Paulo Henrique Rosado de Castro1, Gabriel Cordeiro Camargo1, Adriana Pereira Glavam1, Sergio Altino de Almeida1, Fabio Paiva Siqueira1, Marcelo Teixeira de Holanda2, Luiz Henrique Conde Sangenis2, Fernanda de Souza Nogueira Sardinha Mendes2, Andrea Silvestre de Sousa2 (1) D'Or Institute for Research and Education (IDOR), Rio de Janeiro; (2) Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation Introduction: Chagas disease continues to be an important cause of morbidity and mortality in Latin America. Sudden cardiac death (SCD) represents the most dramatic course of Chagas cardiomyopathy (CC), and it is closely related to the presence of ventricular arrhythmias and myocardial dysfunction. However, there is also a high incidence of SCD when left ventricular ejection fraction (LVEF) is normal or mildly depressed. Unfortunately, despite its significant mortality, there is no clear recommendation for early cardio-defibrillator implantation in patients with CC. Ideally, the risk of SCD should be evaluated in earlier stages of the disease, but important questions remain unresolved regarding its pathophysiological mechanism and the diagnostic tools. New imaging parameters to identify the genesis of arrhythmia such as fibrosis, inflammation and dysautonomia can be a promising strategy. Purpose: We tested the correlation between the extent of myocardial sympathetic denervation, myocardial perfusion, fibrosis and the severity of the ventricular arrhythmia in patients in the early phase of CC. Methods: Twenty-nine patients with CC and LVEF >45% prospectively underwent magnetic resonance (MRI), SPECT imaging of myocardial sympathetic innervation using 123Iodine-MIBG (MIBG) and rest myocardial perfusion with 99mTc-sestamibi (MIBI), and were divided into two groups: arrhythmic group (n = 15): >120 ventricular ectopic beats and/or Non-Sustained Ventricular Tachycardia (NSVT) and non-arrhythmic group (n = 14): <120 ventricular ectopic beats without NSVT on 24-h Holter monitoring. Results: Compared to non-arrhythmic, the arrhythmic group had significantly higher denervation score (mean +- SD 23.2 +- 18.7 versus 5.6 +- 4.9; p < 0.01), higher summed rest perfusion score (mean +- SD 4.7 +- 6.8 versus 0.3 +- 0.6; p < 0.05) as well as the higher mismatch in the innervation/perfusion score between MIBG and MIBI images, which evaluates the extent of denervated but viable myocardium (mean +- SD 18.4 +- 17.5 versus 5.3 +- 4.7; p < 0.01). There was a correlation between myocardium denervation (r 0.555; p < 0.01), hypoperfusion (r 0.562; p < 0.01), and interstitial fibrosis evaluated by extracellular volume at MRI. Conclusion: The combination of different imaging parameters to assess autonomic innervation, myocardial perfusion and fibrosis may allow better understanding of the pathophysiology and risk stratification for SCD in the early stages of CC. 108593 Modality: WHF Abstracts - Researcher Category: NEGLECTED CARDIOVASCULAR DISEASES D: 14/10/2022 H: 13:50/14:50 L: Auditorio 14 Progression of Electrocardiographic Abnormalities in Elderly Chagas Disease Patients During 14 Years of Follow-Up: The Bambui Cohort Study of Aging BRUNO OLIVEIRA DE FIGUEIREDO BRITO1, Bruno Oliveira de Figueiredo Brito1, Emilly Malveira de Lima2, Elsayed Z. Soliman3, Maria Fernanda Lima-Costa4, Antonio Luiz Pinho Ribeiro1 (1) Hospital das Clinicas and Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; (2) Department of Statistics, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; (3) Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA; (4) Instituto Rene Rachou, Fundacao Oswaldo Cruz, Belo Horizonte, Brazil The electrocardiogram (ECG) plays a key role in the evaluation of Chagas disease (ChD). The ECG shows progressive abnormalities that indicate worsening myocardial damage. There is no information about the evolution of the ECG of elderly individuals with ChD. Objective: To compare the evolution of electrocardiographic abnormalities in Trypanosoma cruzi chronically infected individuals to that of the non-infected (NChD) elderly in a follow-up of 14 years of the Bambui Cohort Study of Aging in Brazil. Methods: A digitally recorded 12-lead ECG of each individual was obtained at the baseline examination in 1997, in 2002 and in 2008, and was classified by the Minnesota Code criteria. The influence of ChD on the ECG evolution was assessed by the semi-competing risks methods considering a new ECG abnormality as the primary event and death the terminal event. The group with ChD was compared with the NChD group. A Cox regression model was conducted separately in ChD and NChD groups, in a landmark point at 5.5 years until the end of follow-up. The individuals of both groups were compared according to the following categories: No major: individuals without major abnormalities in the first and second visits; Maintained major: individuals who had the number of major abnormalities in second visit equal to the first visit, More major: individuals who had major abnormalities in the first visit and gained more abnormalities in the second visit and New major: individuals who had no abnormalities in the first visit and gained any major abnormality in the second visit. Results: Among the 1,462 participants, 557 had ChD. The median age was 68 years for patients with ChD and 67 for patients without ChD. Chagas disease was independently associated to the occurrence of new major ECG abnormalities in the multivariate analysis HR: 2.89 (95% CI 2.28-3.67). Compared with the group of ChD No major, the risk of death was HR: 2.48 (95% CI 1.43-4.28) for the Maintained, HR: 1.95 (95% CI 1.04-3.69) for the New major, and HR: 2.77 (95% CI 1.57-4.88) for the More Major. Compared with the group of ChD Maintained major, the risk of death was HR: 0.79 (95% CI 0.44-1.42) for the group New Major and HR: 1.11 (95% CI 0.66-1.89) for the group More Major. Conclusion: Even in advanced ages, the patients with ChD have higher risk than NChD of developing new abnormalities in the ECG. It is enough for individuals with ChD to have ECG abnormalities for their risk of death to increase. 108671 Modality: WHF Abstracts - Young Researcher Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 14/10/2022 H: 16:50/17:50 L: Auditorio 14 Comparison of Adoption of Guideline-Recommended Medical Therapy for Heart Failure Across Global, National, and State Essential Medicine Lists GAUTAM SATHEESH1, Mohammad Abdul Salam2 (1) The George Institute for Global Health, Hyderabad, India; (2) The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia Introduction and/or rationale: Heart failure (HF) is a leading global health burden that disproportionately affects patients in middle-income countries with weaker health systems, such as India. Underutilization of guideline-recommended medical therapy (GRMT)--causing large gaps in evidence and clinical practice--can be mitigated through the adoption of GRMT in the EMLs. Objectives: To compare the adoption of GRMT across the global (WHO) EML and the national and state EMLs of India. Methods: We collated a list of medicines recommended by American (American College of Cardiology Foundation, the American Heart Association, and the Heart Failure Society of America; 2017), European (European Society of Cardiology; 2021), and relevant Indian guidelines (Cardiological Society of India; 2018). We assessed the adoption of these medicines in WHO EML (2021), India's latest national EML (2015), Ministry of Health and Family Welfare's free medicines list (2020), and 23 Indian state EMLs. We only included 'evidence-based medicines', i.e., those supported by relevant randomized controlled trial data for HF. Therefore, we did not include medicines listed as 'commonly used' without relevant evidence. We also excluded medicines listed for use in selected patients only (e.g., milrinone, levosimendan, nesiritide etc.). Results: The adoption of GRMT by WHO EML 2021 was 48% (n = 17), ranging from 75% (beta-blockers) to 0% (SGLT-2 inhibitors). GRMT adoption by Indian EML was 35% (n = 11), ranging from 50% (mineralocorticoid-receptor antagonists) to 0% (SGLT-2 inhibitors). On average, Indian state EMLs contained 36% [18% (Punjab)-53% (Rajasthan)] of GRMT. The lowest adoption (16%; n = 6) was observed in the Ministry of Health's free medicines list, which omitted several major first-line medicine classes. Newly included GRMT, including angiotensin-receptor neprilysin inhibitors and SGLT-2 inhibitors, are yet to be listed in global and national EMLs. Further, at least one emergency medicine was included in all EMLs. Conclusion: Inclusion of GRMT for HF remains suboptimal in the global as well as the national and state EMLs of India. EMLs guide medicine selection and procurement in limited-resource settings. Considering India's increasing cardiovascular disease burden and the potential for EMLs to improve availability and affordability of GRMT, optimizing India's national and state EMLs and particularly its public sector (free medicines) list, is vital. 109112 Modality: WHF Abstracts - Young Researcher Category: NEGLECTED CARDIOVASCULAR DISEASES D: 14/10/2022 H: 16:50/17:50 L: Auditorio 14 Myocardial Perfusion Disturbance in Experimental Chronic Chagas Disease: The Role of Endothelial Inflammatory Activation DENISE MAYUMI TANAKA1, Camila Godoy Fabricio1, Jose A. Marin-Neto1, Antonio Carlos Leite de Barros Filho1, Luciano Fonseca Lemos de Oliveira3, Jorge Mejia4, Rafael Ribeiro Almeida2, Maria de Lourdes Higuchi2, Edecio Cunha Neto2, Minna Moreira Dias Romano1, Marcus Vinicius Simoes1 (1) Medical School of Ribeirao Preto - University of Sao Paulo, Sao Paulo, Brazil; (2) Heart Institute (InCor), Faculty of Medicine - University of Sao Paulo, Sao Paulo, Brazil.; (3) Physiotherapy Department - Federal University of Minas Gerais, Brazil; (4) Hospital Israelita Albert Einstein, Sao Paulo, Brazil. Background: Microvascular myocardial perfusion defect (MPD) is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with the progression of left ventricular systolic dysfunction (LVSD). However, the histopathological meaning of MPD in CCC and its correlation with endothelial activation is scarce. Purpose: To investigate the correlations between MPD detected in vivo with functional and histopathological changes in the model of CCC in hamsters. Methods: 24 female hamsters were studied 8-months after intraperitoneal infection with 35,000 trypomastigote forms of T. cruzi. All animals were submitted to rest high-resolution 99mTc-Sestamibi-SPECT myocardial perfusion scintigraphy and echocardiography in vivo. The area of MPD was assessed by calculating polar maps using dedicated software (MunichHeart(r)). After euthanasia, we performed a histopathological study of cardiac inflammation and fibrosis and mRNA expression for TNF-alfa and ICAM to assess inflammation and endothelial activation, respectively. Results: 17 animals presented MPD (71%) - extension ranging from 1.4 to 30.3% of LV surface. Animals with MPD present lower values of LVEF (38.5 +- 11.2%) when compared with animals without MPD 48.4 +- 9.1%, p = 0.04), and a trend to higher intensity of myocardial inflammation in animals with MPD (540.4 +- 153.6 cell/mm2) vs. without MPD (409.6 +- 130.3 cell/mm2), p = 0.09. In addition, animals with MPD presented a higher ICAM (0.02 +- 0.01) expression when compared with animals without MPD (0.01 +- 0.01, p = 0.02). There was no difference between groups regarding the extent of fibrosis. There was a negative correlation between individual values of MPD with LVEF (R = -0.6, p = 0.001), wall motion score index (WMSi, R = 0.5, p = 0.007), and the number of mononuclear cells (R = 0.5, p = 0.01). Moreover, an analysis based on myocardial segments (n = 312) showed that segments with MPD (n = 54) in comparison to those without MPD (n = 258) presented a higher number of mononuclear cells (608 +- 299.9 cell/mm2 and 478.3 +- 201.1 cell/mm, respectively, p < 0.0001) and higher WMSi (1.8 +- 0.9 and 1.2 +- 0.4, respectively, p < 0.0001. Conclusions: MPD is a common finding in the experimental model of CCC in hamsters and is correlated with inflammation, endothelial inflammatory activation, and systolic ventricular dysfunction. These results suggest that MPD may be an in vivo surrogate marker for inflammation with potential translational implications for monitoring disease activity. 109166 Modality: WHF Abstracts - Researcher Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 14/10/2022 H: 13:50/14:50 L: Auditorio 14 Regional Variation in Women's Awareness of Cardiovascular Disease and its Risk Factors MELANIE B. TURNER, MPH, FAHA1, Laura L. Hayman, PhD, MSN, FAHA2, Dhruv Kazi, MD, MSc, MS, FAHA3, Laxmi S. Mehta, MD, FAHA4 (1) American Heart Association; (2) University of Massachusetts Boston; (3) Beth Israel Deaconess Medical Center; (4) The Ohio State University Medical Center Introduction: Cardiovascular disease (CVD) is the leading cause of death (LCOD) in women globally, causing 9 M deaths annually. Global community awareness data of CVD and its risk factors are limited. Objective: Determine global awareness of CVD incidence and risk factors among women and examine regional variation in awareness. Methods: An online native language survey was administered among nationally representative samples of women >=18 years of age in 50 countries across 6 global regions. The survey was administered June-July 2021 using the YouGov real time omnibus service. The survey included an open-ended question regarding LCOD for women in the country (coded as CVD, cancer, or other/don't know), and a multiple choice question on CVD risk factors. Results were weighted by country, then combined by region. Results: Of 24,100 women, 15.5% reported CVD as LCOD (regional range 6.9-35.0%), 49.4% cancer (23.9-62.9%) and 18.0% other/don't know (9.1-34.4%). Cancer was perceived as LCOD in all regions except South Asia and Middle East and North Africa where other/don't know was the most common response. Regarding CVD risk, 69.5% identified family history as a risk (regional range 51.0-77.1%). Most recognized hypertension, overweight, high cholesterol, and stress. Awareness of diabetes as a CVD risk was low (32.0%, 26.5-44.1%). Conclusions: Awareness of CVD as LCOD among women is low in all global regions. Most women recognize hypertension, high cholesterol, and overweight as risk factors, but awareness of diabetes as a risk factor is low. Efforts are needed in all regions to create awareness of lifetime CVD risk in women, focusing on modifiable risk factors. As an increasingly prevalent global chronic condition, diabetes merits raised attention in community heart health education. 109180 Modality: WHF Abstracts - Researcher Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 14/10/2022 H: 13:50/14:50 L: Auditorio 14 The Impact of Individual-Level Socioeconomic Factors on Maternal and Neonatal Outcomes in Women with Peripartum Cardiomyopathy: An Esc Eorp Registry Study CHARLE ANDRE VILJOEN1, Karen Sliwa1, Peter van der Meer2, Alice M Jackson3, Mark C Petrie3, Cecile Laroche4, Jolien W Roos-Hesselink5, Petar Seferovic6, Alexandra Frogoudaki7, Bassem Ibrahim8, Hasan Al-Farhan9, Johann Bauersachs10 (1) Cape Heart Institute, Department of Medicine and Cardiology, Faculty of Health Sciences, University of Cape Town, South Africa; (2) Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands; (3) Institute of Cardiovascular and Medical Sciences, Glasgow University, Glasgow, United Kingdom; (4) EurObservational Research Programme, European Society of Cardiology, Sophie Antipolis, France; (5) Department Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; (6) University of Belgrade Faculty of Medicine, Belgrade, Serbia; (7) Attikon University Hospital, Athens, Greece; (8) North Cumbria University Hospitals, Carlisle, UK; (9) Iraqi Board of Medical Specilazations, Baghdad Heart Center, Iraq; (10) Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany Background: Peripartum cardiomyopathy (PPCM) is a global disease associated with substantial morbidity and mortality. The aim of this study was to analyze to what extent individual-level socioeconomic factors were associated with maternal and neonatal outcomes. Methods: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EORP Programme. We investigated the characteristics and outcomes of women with PPCM and their babies according to individual (income and educational attainment) and country-specific (Gini coefficient [GINI], health expenditure [HE] and human developmental index [HDI]) socioeconomic status. Results: 739 women from 49 countries were enrolled (Europe [33%], Africa [29%], Asia-Pacific [15%], Middle East [22%]). Women from countries with low HDI had lower income and educational attainment (p < 0.001). Low HDI was associated with greater LV dilatation at time of diagnosis (p < 0.001), but LV ejection fraction (LVEF) did not differ according to HDI, HE or GINI. Countries with low HE prescribed guideline-directed heart failure therapy less frequently (p < 0.001). Low HE was associated with more frequent mortality (p < 0.002), whereas HDI and GINI were not. Women from countries with low HDI and low HE had significantly less recovery of LV function (p < 0.001). Analysis of maternal outcome as per highest level of educational attainment showed significant differences in LVEF at 6 months (43.7 +- 12.9% [primary], 46.5 +- 13.0% [secondary], 48.9 +- 11.7 [tertiary education] respectively, p = 0.022). Low maternal income, irrespective of region of origin, was independently associated with poor outcome (OR 1.99 [95% CI 1.1-3.6] for composite of maternal death, re-hospitalization, or LV non-recovery). Neonatal death was more prevalent in countries with low HE (p = 0.009) and low HDI (p = 0.023) but was not influenced by maternal sociodemographic parameters. Conclusion: Maternal and neonatal outcomes depended on country-specific socioeconomic characteristics, with a greater prevalence of maternal and neonatal deaths in women from countries with low HE. Globally, women with low income and lower levels of educational attainment had poorer outcomes, irrespective of region. Attempts should be made to improve patient education, and allocation of adequate health resources to improve maternal and neonatal outcomes in PPCM. 111430 Modality: WHF Abstracts - Young Researcher Category: NEGLECTED CARDIOVASCULAR DISEASES D: 14/10/2022 H: 16:50/17:50 L: Auditorio 14 Factors Associated with Peak End-Tidal Carbon Dioxide Pressure During Exercise in Patients with Chagas Cardiomyopathy and Systolic Dysfunction WHESLEY TANOR SILVA1, Matheus Ribeiro Avila1, Pedro Henrique Scheidt Figueiredo1, Lucas Frois Fernandes de Oliveira1, Vanessa Amaral Mendonca1, Ana Cristina Rodrigues Lacerda1, Vanessa Pereira Lima1, Henrique Silveira Costa1 (1) Universidade Federal dos Vales do Jequitinhonha e Mucuri UFVJM Introduction: In the functional assessment of patients with Chagas cardiomyopathy, peak oxygen consumption (VO2peak) and ventilatory equivalent of carbon dioxide (VE/VCO2 slope) have already been shown to be parameters of clinical and prognostic relevance. However, other variables assessed by the Cardiopulmonary Stress Test need to be investigated. The peak end-tidal carbon dioxide pressure (PETCO2 peak) has been prominent in the therapy of patients with heart failure. However, its behavior is still unknown in patients with Chagas cardiomyopathy and systolic dysfunction. Objective: To verify, in patients with Chagas cardiomyopathy and systolic dysfunction, the association between peak PETCO2 and functional and echocardiographic parameters. Methods: Seventy-six patients with Chagas cardiomyopathy and systolic dysfunction (49.9 +- 10.8 years, 60% male, NYHA I to III) were recruited and underwent clinical evaluation, echocardiography and Cardiopulmonary Stress Test. Systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) of less than 52 or 54% for men and women, respectively. The variables of interest were PETCO2 peak, VO2peak and VE/VCO2 slope (on Cardiopulmonary Stress Test) and LVEF and left ventricular diastolic diameter (LVd) (on echocardiogram). Results: In the sample, the mean peak PETCO2 was 33.6 +- 4.9 mmHg. In the correlation analysis, PETCO2 peak was associated with VO2peak (r = 0.355; p = 0.008), VE/VCO2 slope (r = -0.626; p < 0.001) and with LVEF (r = 0.299; p = 0.029). There was no correlation between peak PETCO2 and VEd. Conclusion: These results suggest that peak PETCO2 is associated with important clinical and functional parameters of patients with Chagas cardiomyopathy and should be used in the management of patients with Chagas cardiomyopathy. 112213 Modality: WHF Abstracts - Young Researcher Category: NEGLECTED CARDIOVASCULAR DISEASES D: 14/10/2022 H: 16:50/17:50 L: Auditorio 14 Association of Clinical and Genetic Profile in Adults with Aorthopathy - Retrospective Cohort Study with Prospective Follow-Up JULIANA DA ROCHA FERREIRA1, Juliana da Rocha Ferreira1, Julia Passarelli Perreira1, Marcelo Machado Melo1, Helena Cramer Veiga Rey1, Glauber Monteiro Dias2 (1) Instituto Nacional de Cardiologia - INC; (2) Universidade Estadual do Norte Fluminense Darcy Ribeiro - UENF Aortopathies are a silent disease with a high natural fatality rate. Multiple genes have been linked to hereditary aortic thoracic disease (HATD), and it is believed that 30% of people have a deleterious mutation. This study aimed to uncover genetic variations related to aortopathies using genomic and molecular analysis. Seventy-nine people with aortopathies were studied using clinical data, target-NGS (tNGS), and the Sanger sequencing. The ACMG classification was used to find causal variations. This study defined a severe phenotypic population. Aortic dissection occurred in 49.4% of patients diagnosed at 44.59 years old, mainly after 40, and required surgery at 72.2%. Seven pathogenic variants (PV), 4 likely pathogenic variants (LPV), and 22 variants of uncertain significance (VUS) were discovered. tNGS found 10.37 percent of ATDs in this cohort. Direct sequencing of the fibrillin-1 gene (FBN1) yielded 37.5% diagnostic yield for Marfan syndrome suspect individuals, with two PV and one LPV. PV/LPV variants were identified in 6 genes (ACTA2, FBN1, MYLK, SMAD3, TGFB2, TGFBR2), being FBN1 the most prevalent (6 var). Seven PV/LPV are novel variants. Patients with VP/PPV had a younger mean age (39.3 years vs. 44.4 years) and a larger mean aorta diameter (39.3 years vs. 44.4 years) (6.56 vs 5.66 cm), however no statistic significance was achieved. Both groups required surgery (81.8%), with the VP/PVP group having a worse prognosis and severity. An emphasis is placed on clinical suspicion in selecting the genetic test to use and increasing the yield. 111396 Modality: Best Abstracts Oral - Researcher Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION D: 14/10/2022 H: 10:40/11:40 L: Auditorio 14 Inclusion of Cognitive Measures Improves the Predictive Performance of Score2 for Future Cardiovascular Events MARTIN BOBAK1, Steven Hageman2, Hynek Pikhart1, Abdonas Tamosiunas3, Andrzej Pajak4, Ruzena Kubinova5, Wentian Lu1 (1) University College London (UCL), United Kingdom; (2) Utrecht University, Utrecht, The Netherlands; (3) Lithuanian University of Health Sciences, Kaunas, Lithuania; (4) Jagiellonian University Medical College, Krakow, Poland; (5) National Institute of Public Health, Prague, Czech Republic Introduction: The cardiovascular disease (CVD) risk prediction model SCORE2 uses several biomedical and behavioural factors. It is likely that other factors may also contribute to CVD risk prediction. Cognitive impairment and CVD are associated and share some risk factors. While the causality of this relationship remains unclear, adding cognitive measures to risk prediction may be useful for predicting future CVD events. Objective: To test the hypothesis that including simple measures of cognitive functions improve the prediction of SCORE2 for future CVD events. Methods: We used data on 13,391 Polish, Lithuanian and Czech adults without CVD at baseline (45-69 years) from the Health, Alcohol and Psychosocial factors In Eastern Europe cohort. Incident cases of myocardial infarction (MI), stroke, CVD mortality and composite (fatal and non-fatal) CVD events were identified over a 10-year follow-up. Baseline cognitive measures included immediate and delayed word recall (verbal memory and learning), animal naming (verbal fluency) and letter cancellation (attention, mental speed and concentration). Using competing-risks regression, relationships between cognitive functions and CVD outcomes were examined. Improvement in Receiver Operating Characteristic (ROC) was used to compare predictive performance for CVD events of models including SCORE2 variables combined with cognitive tests vs SCORE2 alone. Results: Incidence rates of MI, stroke, CVD mortality and composite CVD events were 5%, 4%, 4% and 11%, respectively. All four cognitive measures were inversely associated with CVD outcomes; e.g. one standard deviation increase in immediate word recall score was associated with a 28% and 17% reduction in risk of CVD mortality and composite CVD events, respectively. Adding cognitive measures to SCORE2 variables improved the ROCs for prediction of MI, CVD mortality and composite CVD events. E.g. for the composite CVD measure, inclusion of all four cognitive measures increased the ROC area from 0.6948 to 0.7030 (p < 0.001) and similar improvement was seen for word recall. Conclusion: Including even a single (and simple) cognitive test in assessment of cardiovascular health can improve prediction of future CVD risk and it may be potentially feasible to do so in general practice. 110777 Modality: Best Abstracts Oral - Researcher Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT D: 14/10/2022 H: 10:40/11:40 L: Auditorio 14 Acute Heart Failure in Patients with Chagas' Cardiomyopathy in Comparison to Other Etiologies: Results of the I Brazilian Heart Failure Registry (Breathe) MARCUS VINICIUS SIMOES1, Pedro Gabriel Barros e Silva2, Denilson Campos Albuquerque3, Renato Delascio Lopes4, Luis Eduardo Paim Rohde5, Lidia Zytinsky Moura6, Fabiana Goulart Marcondes-Braga3, Evandro Tinoco Mesquita3, Jose Albuquerque de Figueiredo Neto7, Ricardo Mourille Rocha8, Joao David de Souza Neto9, Mucio Tavares Oliveira Junior10 (1) Faculdade de Medicina de Ribeirao Preto - USP, Ribeirao Preto, SP, Brasil; (2) Brazilian Clinical Research Institute (BCRI), Sao Paulo, Brazil; (3) Sociedade Brasileira de Cardiologia, Departamento de Insuficiencia Cardiaca - DEIC, Rio De Janeiro, Brazil; (4) Duke Clinical ResearchInstitute, Durham, United States of America; (5) Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; (6) Santa casa, Curitiba, Brazil; (7) Centro de Pesquisa Clinica doHospital Universitario da Universidade Federal do Maranhao (CEPEC-HUUF, Sao Luis, Brazil; (8) PedroErnesto University Hospital, Rio De Janeiro, Brazil; (9) Messejana Hospital, Fortaleza, Brazil; (10) Heart Institute (InCor), University of Sao Paulo Medical School, Brazil Background: Chagas cardiomyopathy (CC) is a prevalent cause of heart failure in Latin America countries. Studies describing clinical manifestations and outcomes of heart failure associated to CC are scarce. Purpose: Report the results of the I Brazilian Heart Failure Registry (BREATHE) addressing the clinical and laboratorial characteristics, and outcomes of patients with acute heart failures (AHF) due to CC in comparison to other etiologies. Methods: BREATHE was a multicenter nationwide prospective registry, enrolling 3,013 adult patients hospitalized with AHF, median follow-up of 346 days. We proceeded the comparative analysis between 261 (8.7%) patients with CC and 2,752 (91.3%) patients with other etiologies, concerning clinical, demographic, cardiac structure/function on Echocardiogram, death rate or heart transplantation during hospital stay and death rate at 3, 6 and 12 months after discharge. The categorical variables were compared by using Fisher Exact test and the continuous variables were compared by using Mann-Whitney test. A multivariate logistic model was used to estimate the odds ratio of CC in 12-month mortality adjusted for clinically relevant variables. Results: CC patients, in comparison to other etiologies, were younger (60.6 +- 13.9 vs 65.7 +- 15.7 y.o., p < 0.001), presented lower systolic blood pressure (108.3 +- 26.1 vs 128.3 +- 30.3 mmHg, p < 0.001), lower heart rate (77.3 +- 22.1 vs 88.5 +- 23.2 bpm, p < 0.001), higher rate of jugular vein distension (54.8% vs 38.9%, p < 0.001) and hepatomegaly (47.9% vs 25.6%, p < 0.001), higher rate of "cold and wet" clinical hemodynamic profile (27.2 vs 10.6%, p < 0.001); larger diastolic left ventricular (LV) diameters (65 [57-72.8] vs 59 [51-66] mm, p < 0.001), and lower LV ejection fraction (25.4 [19-36]% vs 37 [27-54]%, p < 0.001), with higher rates of dobutamine use (23.8% vs 6.8%, p < 0.001); presented higher rate of death or heart transplantation during hospital stay (11.1% vs 17.4%, p = 0.004), and higher cumulative death rate after discharge at 3-months (16.5% vs 10.8%, p = 0.017, at 6-months (25.7% vs 17.5%, p = 0.006, and at 12-months (40.8% vs 27.8%, p < 0.001). In a multivariate analysis, CC was independently associated with 12-month mortality risk with odds ratio = 2.02 [95% IC: 1.47;2.77]. Conclusions: Patients hospitalized with AHF with CC etiology, in comparison to other etiologies, presented higher-risk profile that was associated with a poorer outcome during hospital stay and after discharge. 111321 Modality: Best Abstracts Oral - Researcher Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS D: 14/10/2022 H: 10:40/11:40 L: Auditorio 14 In-Hospital Program to Systematize Chest Pain Protocol (In-Hope) PEDRO GABRIEL MELO DE BARROS E SILVA1, Ana Amaral3, Antonielle Figueiredo Macedo4, Celso Musa Correa5, Eduardo Zincone6, Marcelo Paiva Cury7, Gustavo Augusto Lopes Rosa8, Alexandre de Matos Soeiro9, Carlos Alexandre Lemes de Oliveira10, Augusto Celso De Araujo Lopes Junior11, Adriana Bertolami7, Renato Delascio Lopes12 (1) Hospital Samaritano Paulista; (2) Cardiologia Americas; (3) Hospital Pro-cardiaco; (4) Hospital da Luz; (5) Americas Medical City; (6) Hospital Santa Helena; (7) Metropolitano Lapa; (8) Ipiranga Mogi; (9) Incor HC FMUSP; (10) Hospital Paulistano; (11) Hospital Monte Klinikum; (12) Brazilian Clinical Research Institute Background: Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation in order to exclude the diagnosis of acute myocardial infarction (AMI). Recent algorithms using high-sensitivity cardiac troponin assays at 0 h and 1 h are accepted as a rule-out/rule-in strategy but there is a lack of validation in specific populations. Methods: IN-HOPE was a multicentre prospective study that included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. All patients followed the standard approach of 0-3h but, in addition, blood samples were also collected at 0 and 1 hour and sent to a core laboratory to measure high sensitivity troponin T (hs-cTn T) Elecsys (Roche). Troponin <12 ng/L with a delta <3 was considered rule out while a value >=52 and/or a delta >=5 was considered rule in for AMI. The main objective of the study was to assess the accuracy of 0-1 h rule-out/rule-in algorithm in comparison to the standard of care (0-3h). All patients were followed for 30 days. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTn T measured during 2021 but not included in the prospective cohort. Results: A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (+-14.8) and 45.6% of females with a mean HEART score of 4.0 +- 2.2. By the core lab analysis, 71.6% would be eligible for a rule-out approach while 7.3% would fit the rule-in criteria. At 30 days, no death or AMI occurred in the rule-out group while 64.9% of the patients in the rule-in group were considered as AMI. In the retrospective analysis, 1.091 patients had a troponin value <5 ng/L without cardiovascular deaths in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group <5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L and 7.7% in the level >=90 ng/L. Conclusions: In this large multicentre Brazilian study, a 0-1h algorithm was effective for classifying as rule in or out almost 80% of the patients. The rule-out protocol had high negative predictive value regardless clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for the group with values <5 ng/L. 112023 Modality: Best Abstracts Oral - Researcher Category: CARDIOVASCULAR SURGERY D: 14/10/2022 H: 10:40/11:40 L: Auditorio 14 Perioperative Cardiovascular Events and Mortality After Cardiac Surgery Across the Spectrum of Chronic Kidney Disease LUIS EDUARDO PAIM ROHDE1, Marcio R. Martins1, Luis E. Rohde1, Flavia K. Borges2, Andre Lamy2, Richard Whitlock2, P. J. Devereaux2, Carisi A. Polanczyk1 (1) Hospital de Clinicas de Porto Alegre, Post Graduate Program in Cardiovascular Sciences and Cardiology, UFRGS; (2) McMaster University, Hamilton Health Sciences Background: Previous studies addressing the association of chronic kidney disease (CKD) and prognosis after open-heart surgery had limited sample sizes and retrospective designs. Methods: We investigated the association of preoperative renal function and in-hospital mortality, and major cardiac and cerebrovascular events (MACCE) in patients enrolled in the prospective multicentric VISION Cardiac Surgery Study. Patients were divided in 5 CKD stages according to preoperative estimated glomerular filtration rate (eGFR in mL/min/1.73 m2): Stage I(>90; n = 1914), Stage II(60 to 89; n = 8122), Stage III(30 to 59; n = 3406), Stage IV(<30; n = 352) and Stage V(dialysis; n = 227). Results: 15,837 were included in the current analysis (71% male, 66% hypertensive and 20% >75 y.o.). Mortality and MACCE during the first 30 days occurred in 480(3%) and 1727(11%) patients, respectively. Logistic regression models adjusted for EuroSCORE demonstrated increased 30-day mortality in CKD Stage III (odd ratio[OR], 1.82; 95% confidence internal[CI], 1.36-2.41), CKD Stage IV (OR, 2.62; 95% CI, 1.66-4.15) and in patients in dialysis (OR, 3.56; 95% CI, 2.17-5.85) In analysis across the whole spectrum of renal function , mortality was increased particularly when eGFR was <45 mL/min/1.73 m2, while MACCE risk was observed in less severe stages of CKD. Conclusion: In this contemporary cohort, CKD was significantly associated with morbidity and mortality after open-heart surgery. 112135 Modality: Best Abstracts Oral - Researcher Category: DIGITAL HEALTH/INNOVATION D: 14/10/2022 H: 10:40/11:40 L: Auditorio 14 Combining Long-Term Predictive Windows Improve Risk Estimation of Adverse Cardiovascular Outcomes Among Individuals with Premature Acute Coronary Syndromes LUIZ SERGIO FERNANDES DE CARVALHO1, Gustavo Alexim5, Ana Claudia Cavalcante Nogueira3, Marta Duran Fernandez1, Tito Barbosa Rezende4, Sandra Avila4, Ricardo Torres Bispo Reis6, Alexandre Anderson Munhoz Soares3, Andrei Carvalho Sposito4 (1) Clarity: Inteligencia em Saude; (2) Universidade Catolica de Brasilia; (3) Instituto Aramari Apo; (4) UNICAMP; (5) Hospital de Base do Distrito Federal; (6) Universidade de Brasilia Introduction: Among individuals with premature acute coronary syndromes (prACS, <55 years-old), prevalent risk factors and the magnitude of their impact on recurrent ischemic events critically differ from older subjects. In that sense, it is plausible to develop risk prediction rules specific for young individuals. Our aim was to evaluate potential improvements in risk prediction quality among prACS by (i) developing models specifically in prACS subjects versus in the global cohort; (ii) splitting predictive rules into two models ( long-term prediction windows [STWm and LTWm]) versus a global follow-up model (GFm). Methods: Consecutive individuals with ACS who undergone coronarography up to 48h after hospital admission from January/2011 to February/2020. 6341 subjects (2242 with prACS) admitted into public hospitals in Brasilia (Brazil). The observation window in STWm and GFm included the first 48h upon hospital admission, and LTWm included all in-hospital information. prACS cohort was divided into train/validation-set (70%, n = 1569) and test-set (30%, n = 673); global cohort was divided in training/validation-set (70%, n = 4439) and test-set including the 673 prACS subjects. Models were repeated over five cross-validation folds and then assessed in the test-set. C-statistics was the evaluation metric for STWm and time-dependent concordance (Ctd-index) for LTWm. STWm evaluated the occurrence of in-hospital cardiovascular deaths and recurrent ACS (MACE) and LTWm estimated events occurring post-discharge from index ACS hospitalization considering time-to-event with competing risks (MACE versus non-cardiovascular deaths). Results: Median follow-up of 6.7 years (95%CI 5.6-7.2). Among prACS and older subjects, respectively, in-hospital MACE occurred in 180 and 493 individuals, post-discharge MACE in 454 and 881; and post-discharge non-cardiovascular death in 47 and 285. The best strategy was to design models specifically in prACS individuals combining STWm and LTWm. Among prACS subjects STWm and LTWm, respectively, TabNet and DeepHit yielded the best C-statistics [0.921 (95%CI 0.889-0.953)] and Ctd-index [0.722 (95%CI 0.678-0.760)], while the best Ctd-index in GFm was 0.681 (95%CI 0.654-0.703). There was very low concordance among top predictors of MACE for prACS versus global cohort, as well as for STWm versus LTWm. Conclusions: Risk prediction in ACS is optimized by using specific rules for prACS and combining short-term and long-term prediction windows. 109042 Modality: Best Abstracts Oral - Young Researcher Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE D: 14/10/2022 H: 09:00/10:00 L: Auditorio 14 Landscape of Heart Proteome Changes in Exercised Aortic Stenosis Rats GUSTAVO AUGUSTO FERREIRA MOTA 1, Sergio Luiz Borges de Souza1, Danielle Fernandes Vileigas2, Vitor Loureiro da Silva1, Paula Grippa Sant'Ana1, Licia Carla Silva Costa3, Silmeia Garcia Zanatti Bazan1, Marilia Afonso Rabelo Buzalaf4, Lucilene Delazari dos Santos5, Marina Politi Okoshi1, Mariana Gatto1, Antonio Carlos Cicogna1 (1) Sao Paulo State University, UNESP, Botucatu Medical School, Brazil; (2) University of Sao Paulo, USP, Institute of Chemistry, Brazil; (3) University of Campinas, UNICAMP, Institute of Biology, Brazil; (4) University of Sao Paulo, USP, Bauru Dental School, Brazil; (5) Sao Paulo State University, UNESP, Biotechnology Institute, Brazil Introduction: The beneficial effect of aerobic exercise training (ET) on cardiac remodeling induced by aortic stenosis (AS) has been observed in experimental studies. However, the mechanisms involved in cardiac function improvement are not fully understood. In this study we investigated the myocardial proteoma in rats with AS subjected to ET. Methods: Wistar rats (n = 60, 21 days) were divided into 2 groups: operated control (C) and supravalvar aortic stenosis (AS). AS was induced by the insertion of a stainless-steel clip, 0.60 mm, around the ascending aorta. Two weeks after surgery, rats were assigned into 4 groups: C, exercised C (C-Ex), AS and exercised AS (AS-Ex). Exercised rats underwent treadmill exercise 5 days a week for 4 months, at 60% of the maximal functional capacity. Two and 18 weeks after surgery, rats were subjected to echocardiogram. Functional capacity was analyzed by treadmill maximum exercise testing and blood lactate concentration. Myocardial proteome was assessed by label-free shotgun approach using mass spectrometry. Protein expression was quantified by Western blotting. Statistical analysis was performed by ANOVA or Kruskal-Wallis; significance level of 5%. Results: Two weeks after AS induction, AS rats had diastolic and systolic dysfunction and concentric hypertrophy. At the end of the protocol, AS maintained the same remodeling pattern; the AS-Ex group presented lower left atrium diameter-to-aortic diameter and lactate concentration; and higher E/E' ratio, percentage of midwall fractional shortening, and functional capacity than AS. After enrichment analysis by Gene Ontology, myocardial proteome analysis showed higher expression of proteins related to glycolytic pathway, oxidative stress, and inflammation, and lower expression of proteins associated with beta-oxidation in AS than C. The AS-Ex had higher expression of proteins related to mitochondrial biogenesis and lower expression of proteins related to oxidative stress and inflammation than AS. Expression of proteins of physiological and pathological hypertrophic pathways did not differ between groups, except for p-p38, which was higher in the AS than C group. Conclusion: Aerobic exercise training improves cardiac remodeling and mitochondrial biogenesis, and attenuates oxidative stress and inflammation in rats with ascending aortic stenosis. Financial support: CNPq, FAPESP, and UNESP. 108618 Modality: Best Abstracts Oral - Young Researcher Category: PHYSICAL EDUCATION D: 14/10/2022 H: 09:00/10:00 L: Auditorio 14 Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation in Young Male Anabolic Androgenic Steroids Users FRANCIS RIBEIRO DE SOUZA1, Carlos Eduardo Rochitte1, Douglas Carli Silva1, Andre Matheus Rodrigues Gomes1, Marcelo Rodrigues dos Santos1, Guilherme Wesley Peixoto da Fonseca1, Antonio Carlos Battaglia Filho1, Kelly Thayane Souza Correa1, Mauricio Yonamine2, Rosa Maria Rodrigues Pereira3, Carlos Eduardo Negrao1, Maria Janieire de Nazare Nunes Alves1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (InCor, HCFMUSP); (2) Faculdade de Ciencias Farmaceuticas da Universidade de Sao Paulo (FCF/USP); (3) Laboratorio de Reumatologia e Metabolismo Osseo da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP) Background: The illicit use of anabolic androgenic steroids (AAS) has been associated with diminished cholesterol efflux mediated by HDL, remarkable decrease in high-density lipoprotein (HDL) plasma concentration and subclinical coronary artery disease (CAD). Inflammation is the key to the atherogenic process associated with atherosclerotic plaque vulnerability. The pericoronary mean fat attenuation (pFAM) has emerged as a marker of coronary inflammation and can predict future cardiovascular events, which is measurable from standard coronary computed tomography angiography (CCTA). However, whether AAS abuse has a role in pFAM in young male AAS users is unknown. Purpose: The aim of this study was to evaluate whether AAS abuse could leads to higher pFAM and premature coronary inflammation in young male AAS users. Methods: Twenty strength-trained AAS users (AASU) age 29 +- 5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this study. Coronary inflammation was assessed by pFAM-CCTA in the right coronary artery (RCA), left anterior descending artery (LDA) and left circumflex coronary artery (Cx). Results: pFAM in RCA was significantly higher in AASU compared with AASNU and SC (-64.59 +- 9.45 vs. -79.21 +- 6.67 vs. -80.97 +- 7,91 Hounsfield Units (HU), respectively, p < 0.001]. Also, the pFAM in the LAD was higher in AASU compared with AASNU and SC (-72.83 +- 7.21 vs. -79.41 +- 6.72 vs. -80.97 +- 7.72 HU, p = 0.006). However, no difference to pFAM in the Cx between AASU, AASNU and SC (-74.30 +- 5.85 vs. -79.77 +- 7.13 vs. -78.19 +- 5.82 HU, respectively, p = 0.069) was found. Conclusion: This study indicates that AAS abuse may be associated with higher pFAM and premature coronary inflammation in the RCA and LAD. In addition, the higher pFAM may be linked to early development of CAD in young AAS users. 109119 Modality: Best Abstracts Oral - Young Researcher Category: DIGITAL HEALTH/INNOVATION D: 14/10/2022 H: 09:00/10:00 L: Auditorio 14 Utilizing Automated Machine Learning for Rheumatic Heart Disease Detection in Doppler Echocardiography KELSEY BROWN1, Pooneh Roshanitabrizi, PhD3, Alison Reese, MS1, Andrea Beaton, MD2, Emmy Okello, PhD4, Joselyn Rwebembera, MMed4, Peter Lwabi, MMed4, Emma Ndagire, MMed4, Craig Sable, MD1, Marius George Linguraru, DPhil3 (1) Children's National Hospital; (2) Cincinnati Children's Hospital Medical Center; (3) Sheikh Zayed Institute for Pediatric Surgical Innovation; (4) Uganda Heart Institute Introduction: Rheumatic heart disease (RHD) is the number one cause globally of morbidity and mortality from heart disease in children and young adults. The mitral regurgitation (MR) jet length on color Doppler echocardiography is an important index for diagnosis, but its measurement and interpretation are variable. Objective: Develop an automatic machine learning approach to identify and measure the MR jet length on color Doppler for RHD detection. Methods/Design: We used 316 echocardiograms in video format from 95 children (mean age 12 +- 2 years; range 5 to 17 years) with DICOM color Doppler images of the mitral valve taken from parasternal long axis (PLAX) and apical 4 chamber (AP4) views. All echocardiograms were independently reviewed by an adjudication panel which consisted of four expert pediatric cardiologists to determine maximum MR jet length and diagnosis (RHD positive or not). Among 95 cases, 29 were normal and 66 had RHD. Our automated method included. (1) Selection of frames during ventricular systole using a convolutional neural network architecture based on the ResNet-50. (2) Localization of left atrium using convolutional neural networks with LinkNet structure. (3) Measurement of MR jet length using image color analysis. (4) Detection of RHD by applying a generalized regression model based on the maximum MR jet length measured on each view and maximizing the balanced accuracy using cross validation. Results: Machine learning selected the correct systolic frame with an average accuracy of 0.95 (sensitivity 97%/specificity 93%) and 0.94 (sensitivity 94%/specificity 94%) for the AP4 and PLAX view, respectively. It localized the atrium with an average Dice coefficient of 0.89 and 0.9 for the AP4 and PLAX view, respectively. We estimated the length of the MR jet with an average absolute error of 0.33 +- 0.4 cm (p-value = 0.15 compared to manual measurements). Our deep learning approach performed similar to or better than previously published manual methods for categorization of RHD positive vs negative. The accuracy of RHD detection was 0.84 (sensitivity 86%/specificity 79%). Conclusion: Our automatic method has the potential to reliably detect RHD as accurately as expert cardiologists. This innovative approach holds promise to scale echocardiography screening for RHD and greatly expand prophylaxis to prevent progression of RHD globally. 109213 Modality: Best Abstracts Oral - Young Researcher Category: CARDIO-ONCOLOGY D: 14/10/2022 H: 09:00/10:00 L: Auditorio 14 Impact of High-Intensity and Moderate-Intensity Training on Cardiometabolic Variables in Oncological Patients with Newly Diagnosed Cardiovascular Disease. Randomized Clinical Trial JAVIER ELIECER PEREIRA RODRIGUEZ1, Fernando Rivera-Theurel2, Jorge Antonio Lara-Vargas3, Devi Geesel Penaranda-Florez1, Pedro Pereira-Rodriguez4, Karla Dominguez-Gomez1, Kelly Perez-Diaz1, Dafne Palacios-Toledo1, Hiady Rivera-Lopez1, Alondra Mijangos-Dolores1, Isaias Sanchez-Garcia1 (1) Centro de Estudios e Investigacion FISICOL; Colombia; (2) University of Toronto; Canada; (3) Cardiofit; Mexico; (4) Clinica Medical Duarte; Colombia Introduction: Cardio-Oncology aims to prevent and treat cardiac dysfunction induced by anti-oncological therapies. One emergent strategy is the physical activity, which has been considered an important strategy to improve quality of life and outcomes in the susceptible population. Objective: Determine the cardiovascular effects of Moderate Intensity Continuous Training (MICT) and High Intensity Interval Training (HIIT) on oncological patients newly diagnosed with cardiovascular disease (CVD). Methodology: Randomized controlled trial with sample of 690 with oncological patients with a new diagnose of CVD (heart failure and ischemic heart disease) distributed in 3 groups (MICT, HIIT and control group). We identified the echocardiogram, cardiac biomarkers, stress test, clinical and hemodynamic parameters, hematological samples were identified. In addition, 6-minute walk, anthropometry, quality of life, fatigue, sarcopenia. The tests were performed pre and post 36 sessions of 70-minute training. Then, descriptive statistics were carried out to estimate, the normality of the data was assessed by the Kolmogorov-Smirnov test and the indication of specificity was evident for all analyzes. Also, the ANOVA analysis of variance (one-way analysis of variance) was used, and subsequently, post hoc tests with Tukey test. In all cases, a significance level was 5% (p = <0.05). Results: After an structured exercise program, there was an increase in left ventricular ejection fraction (LVEF) (EG1: 40 +- 5 vs 44 +- 4%; EG2: 41 +- 4 vs 47 +- 3%; CG: 40 +- 3 vs 40 +- 1%; p < 0.05). In fact, higher values of functional capacity (VO2peak) were noted in the experimental group 2-HIIT (7.0 +- 5.2 vs 9.7 +- 3.7) compared to experimental group 1-MICT (8.0 +- 4 vs 8.5 +- 3) and control group (9.0 +- 5.0 vs 9.2 +- 4.0). Other parameters results incuded systolic blood pressure (135 +- 10 vs 127 +- 2 mmHg), diastolic blood pressure (85 +- 5 vs 80 +- 2 mmHg), maximum heart rate (166 +- 10 vs 179 +- 5bpm) and quality of life (106 +- 8 vs 73.2 +- 11). It was possible to show significant changes in all variables comparing HIIT vs MICT groups (p = <0.05), and also compared to the control group. Conclusions: HIIT and MICT in oncological patients with newly diagnosed CVD improved the LVEF, functional capacity (VO2peak), hemodynamic parameters (systolic and diastolic blood pressure), exercise tolerance, depression, anxiety, strength, Cancer related fatigue improved as well as other specific cancer variables such as sarcopenia, and quality of life. 109929 Modality: Best Abstracts Oral - Young Researcher Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION D: 14/10/2022 H: 09:00/10:00 L: Auditorio 14 Effectiveness of Influenza Vaccination as a Secondary Prevention Therapy for Coronary Artery Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials LETICIA MARA DOS SANTOS BARBETTA1, Leticia Mara dos Santos Barbetta1, Eduardo Thadeu de Oliveira Correia1, Ronaldo Altenburg Odebrecht Curi Gismondi1, Antonio Jose Lagoeiro Jorge1, Evandro Tinoco Mesquita1 (1) Universidade Federal Fluminense; (2) Instituto Cardiovascular do Complexo Hospitalar de Niteroi; (3) Centro de Educacao e Treinamento Edson Bueno - UnitedHealth Group; (4) Hospital Niteroi D'Or Introduction: Previous randomized trials showed conflicting results regarding the effectiveness of influenza vaccination on cardiovascular outcomes in patients with coronary artery disease (CAD). These studies were not adequately powered to show the effectiveness of influenza vaccine on major adverse cardiovascular events (MACE); all-cause mortality or cardiovascular mortality. Therefore, this up-to-date meta-analysis combines data from randomized trials to assess the effectiveness of influenza vaccination on endpoints in patients with CAD. Methods: We performed a search of the Cochrane Controlled Register of Trials, Embase, MEDLINE, www.ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from inception to September 2021. Two authors performed the screening, quality analysis and data extraction. A p-value <0.05 was defined as statistically significant. This study protocol is available in PROSPERO under the following registration number CRD42021282917. Results: We identified 355 records through search of databases. After duplicate analysis, 258 articles remained, of which 239 were excluded based on title and/or abstract analysis. Nineteen full-text articles were assessed for eligibility, and 5 articles were selected for inclusion. Five trials were included in this meta-analysis, comprehending 4238 patients, from which 2116 were controls and 2122 received influenza vaccination. Influenza vaccination reduced all-cause mortality compared with placebo (RR 0.50, CI 0.29-0.88, p = 0.02). However, in a prespecified subgroup analysis, influenza vaccination only reduced all-cause mortality in patients with acute coronary syndrome (ACS) (RR 0.44, CI 0.23-0.82, p = 0.01), but not in stable CAD (RR 1.02, CI 0.32-3.31, p = 0.97). Moreover, influenza vaccination reduced cardiovascular mortality compared with placebo (RR 0.54, CI 0.37-0.80, p = 0.002). Regarding MACE, influenza vaccination was effective compared with placebo (RR 0.65, CI 0.48-0.88, p = 0.005), especially in ACS (RR 0.58, CI 0.39-0.87, p = 0.007), although it was not effective in stable CAD (RR 0.91, CI 0.54-1.54, p = 0.72). Conclusions: The results of this meta-analysis shows that influenza vaccination is effective to reduce all-cause mortality, cardiovascular mortality and MACE among patients with CAD, especially those with ACS. Healthcare strategies must be outlined to deliver this cheap and effective intervention in order to reduce hard outcomes for CAD patients. 109253 Modality: Best Abstracts Oral - Scientific Initiation Category: COVID-19 AND CARDIOVASCULAR SYSTEM D: 13/10/2022 H: 15:40/16:40 L: Auditorio 05 Endothelial Dysfunction, Hypercoagulable State, and Thrombosis in Patients who Died from Covid-19 NICHOLAS VINCENT LEE1, Nicolas Henrique Borges1, Thiago Mateus Godoy1, Sabriany Nunes Mendes1, Anna Flavia R S Miggiolaro1, Rafaela C Zeni1, Lucas Baena Carstens1, Marcos Roberto Curcio Pereira1, David Batista Wiedmer1, Marina Luise Viola de Azevedo1, Lucia de Noronha1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DO PARANA - PUC/PR Introduction: Vascular endothelial cells are involved in the immune response mediated by SARS-CoV-2, which, when activated, has a significant influence on cell stability, culminating in edema, thrombosis, and endothelial dysfunction. The pathways responsible for this endotheliopathy process are still being discussed in the literature. Therefore, the analysis of the vascular events involved in the disease is necessary to concatenate findings that justify the cardiovascular repercussions. Objective: Evaluate the tissue expression of endothelium dysfunction markers, Intercellular Adhesion Molecule 1 (ICAM-1), angiotensin 2 (ANGIO-2), interleukin-1-b (IL1b), and Von Willebrand Factor (VWF) and correlate with endothelial activation/dysfunction in the vascular endothelium of lung samples from COVID-19 patients and compare with H1N1 and control cases. Method: The study analyzed post mortem lung samples (COVID-19 group = 20 cases; Group H1N1 = 10 cases and control group = 11 cases) through immunohistochemistry, using the primary monoclonal antibody of anti-ICAM-1, anti-ANGIO 2, anti-IL1b, and anti-VWF. The immunostained slides were scanted and selected by blinding. Then, software was responsible for quantifying the tissue expression of ICAM-1, ANGIO-2, IL-1b, and VWF obtained in each case. The findings were compared using the Kruskal-Wallis nonparametric test. Results: The histopathological characteristics of pulmonary vascular damage caused by H1N1 differ from those observed in the COVID-19 group. For ICAM-1, an increase in expression was observed with statistically significant (p < 0,0001) when comparing the COVID group with both the control and H1N1 groups. The same pattern was repeated in the expression of IL-1b. Although, for ANGIO-2 and VWF, there was no statistical significance when comparing the COVID group with H1N1 (p > 0,05), when comparing the COVID group with the control group, the expression of these markers was higher (p < 0,05). In addition, there are no significant fibrinous thrombi or neutrophilic endotheliitis present in patients infected with H1N1. Conclusions: Our results demonstrated endothelium activation and dysfunction secondary to cytokine storm. The endothelial injury and the state of hypercoagulability caused by COVID-19, when added to the blood stasis present in bedridden patients, culminating in the formation of the Virchow triad, capable of elevating the chances of systemic thrombotic events and cardiovascular repercussions. 111707 Modality: Best Abstracts Oral - Scientific Initiation Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT D: 13/10/2022 H: 15:40/16:40 L: Auditorio 05 A New Score Based on Machine Learning to Predict In-Hospital Death in Patients with Acute Heart Failure: The ML-HF Score JORGE TADASHI DAIKUBARA NETO1, Jorge Tadashi Daikubara Neto1, Matheus Bissa Duarte1, Gustavo Sarot Pereira da Cunha1, Leonardo Henrique dos Santos de Melo1, Michelle Bozko Collini1, Carolina Ruschel Senger1, Jessica Tamires Reichert1, Raphael Henrique Dea Cirino1, Sabrina Bernardez2, Fabio Papa Taniguchi2, Miguel Morita Fernandes-Silva1 (1) Hospital de Clinicas - UFPR; (2) Hospital do Coracao - HCor Introduction: Acute Heart Failure (AHF) has high mortality and identifying those patients with worse prognosis helps guiding their management. However, current available prognostic assessment scores have sub-optimal performance, so they are rarely used in clinical practice. Objective: Developing and validating a machine learning-based prognostic score to predict in-hospital death in patients with AHF and compare its performance with the Acute Decompensated Heart Failure National Registry (ADHERE) and the Get With the Guidelines-Heart Failure (GWTG-HF) scores. Methodology: We included patients admitted with AHF in 17 brazilian hospitals participants of a multicenter study from 2016 to 2019. Clinical, laboratory and echocardiographic data and the WHOQOL-BREF quality of life questionnaire at hospital admission were used as covariates. The outcome was in-hospital death from any cause. Machine learning prediction models - using Random Forest, Gradient Boosting Machines, and Deep Neural Networks - were applied in 70% of the sample (training set) to develop the score (ML-HF score), which was validated on the 30% remaining of the sample (test set). Results: From 2657 patients hospitalized for AHF, we included 887 [59% men, 61.6 +- 14.5 years, ejection fraction 41.8 +- 17.2%, 84 (9%) died] who had complete data. The five most important variables of the ML-HF score were: Physical Health Domain quality (WHOQOL-BREF), serum sodium, serum urea, serum creatinine and systolic blood pressure at hospital admission. In the test set, the ML-HF score showed good model calibration (Hosmer-Lemeshow test p value = 0.124) and good model discrimination area under the ROC curves [(AUC) = 0.739 (95%CI,0.652-0.825)], which was better than the GWTG-HF [AUC = 0.601 (IC95%, 0.459-0.743)], p = 0.05 and the ADHERE [AUC = 0.594(IC95%, 0.445-0.742)], p = 0.05 scores (figure). Conclusion: We developed and validated a score using machine learning to predict in-hospital death in patients with AHF, which outperformed the ADHERE and GWTG-HF scores. 111880 Modality: Best Abstracts Oral - Scientific Initiation Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 13/10/2022 H: 15:40/16:40 L: Auditorio 05 Heart Transplant: Trends in Brazilian Epidemiology between 2008 and 2021 BEATRIZ SALES DE FREITAS1, Ana Carolina Sampaio Freire1, Caio Resende da Costa Paiva1, Isabel Gomes da Silva1, Gabriel Haiek Fernandes1, Gabriela Goncalves Almeida1, Maria Luiza Marinho de Sa de Paula Lima1 (1) Universidade de Brasilia (UnB) Introduction: Heart transplant (HT) is one of the main surgeries by which patients with advanced and refractory heart failure can prolong their lives. Nonetheless, its complexity requires a well prepared staff and abundant financial resources, which can be a challenge in developing countries such as Brazil. In this scenario, searching for trends in epidemiology and regional disparities is key to scale the problem and propose interventions. Objectives: To analyze data of HT in Brazil's different regions between January 2008 and December 2021. Methodology: Epidemiological inquiry based on data related to mortality rates and annual HT absolute numbers from 2008 to 2021 in Brazil. The data was obtained through the public domain national platform TABNET from the Informatic Department of the Brazilian Universal Healthcare System. A comparative analysis of data was made, in addition to complementary research in recent literature. Results: From January 2008 to December 2021, 3.368 HTs were performed in Brazil. The main causes for HT were Ischemic Cardiomyopathy, followed by Congestive Heart Failure and Chagasic Cardiomyopathy. The majority of HTs were in the Southeast (n = 1792). In contrast, in the North, which doesn't have specialized centers, no surgeries were performed (n = 0). It is possible to recognize an increase in the absolute number of procedures throughout the period analyzed followed by a decrease in the last two years. This decrease may be a consequence of the COVID-19 pandemic. Despite the upward trend described, the number of capacitated teams or centers remained fairly the same from 2014 to 2021. Regarding the mortality rates, 13,62% of the patients who underwent HT died in the procedure or in post-op care at the health service. In general, these mortality rates have been declining, going from 20,99% in 2018 to 9,27% in 2021, a possible effect of the evolution in transplant techniques. HTs represent a challenge for Brazil's health system. In December 2021, 321 patients were waiting for the surgery. Compared to kidney, cornea and liver transplants, HT boasts one of the higher discrepancies between performed versus demanded transplants. Conclusion: HT is a highly complex procedure that requires proper logistics, training, resources and specific post-op care, representing a challenge for Brazil's public health system. Considering the demand of HTs in Brazil, it is necessary to create new centers and to train new teams, especially in the North. 112045 Modality: Best Abstracts Oral - Scientific Initiation Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 13/10/2022 H: 15:40/16:40 L: Auditorio 05 Hypercholesterolemia and Mortality from Ischemic Heart Diseases in American Men LUIZ FELIPE FACANHA RAMOS1, Karen Tassia Facanha Ramos1, Hildeman Dias da Costa2, Ayrison Melo Sousa3, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia; (3) Centro Universitario UNINORTE Introduction: The increase in the amount of low-density lipoproteins (LDL cholesterol) or hypercholesterolemia is considered one of the factors in the occurrence and mortality of cardiovascular and cerebrovascular diseases, especially ischemic heart disease (IHD). Objective: To relate hypercholesterolemia and IHD mortality in men in the countries of America in the year 2018. Methodology: This is an analytical ecological study of geographic distribution with secondary data from the Health Information Platform for the Americas (PLISA), of the Pan American Health Organization (PAHO), of the year 2018, on the averages of total cholesterol and fractions and the mortality rates due to IHD in men in the countries of the American continent. The rates were standardized per 100,000 inhabitants with a confidence interval (CI) of 95%. Results: Guyana had the highest IHD male mortality rate (228.9; 95% CI 175.8-312.7) in 2018 in America, followed by Haiti with the 2nd highest rate (190.3; 95% CI 124.6-278.8). In contrast, Peru has the lowest rate (46.6; 30.4-66.6) in the same year. In addition, it was shown that Guyana has men with the highest mean LDL cholesterol (x = 3.81; 95% CI 3.56-4.05). It is noteworthy that Venezuela was the country with the lowest mean LDL cholesterol (x = 3.23; 95% CI 3.03-3.41), despite having the third highest mortality rate in South America (130.9; 95% CI 98.9-169.1). Conclusions: There is a positive linear correlation between high LDL cholesterol and mortality in men from IHD in America, as Guyana has the highest mortality rate and the highest mean LDL cholesterol in men in 2018. This suggests that public policies should be directed to combat hypercholesterolemia that can significantly increase mortality from ischemic heart disease. 112186 Modality: Best Abstracts Oral - Scientific Initiation Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT D: 13/10/2022 H: 15:40/16:40 L: Auditorio 05 Regional Characteristics of HFrEF in Brazil: Rosa Dos Ventos Study DHAYN CASSI DE ALMEIDA FREITAS1, Jefferson Luiz Vieira2, Sabrina Bernardez Pereira3, Fabiana Goulart Marcondes-Braga4, Wilson Nadruz Junior5, Silvia Marinho Martins Alves6, Gabriela Arcoverde Wanderley7, Jessica Tamires Reichert8, Jose Albuquerque de figueiredo neto9, Alana de Oliveira Castro9, Miguel Fernandes da Silva Morita8, Odilson Marcos Silvestre1 (1) Universidade Federal do Acre; (2) Hospital de Messejana - Dr. Carlos Alberto Studart Gomes; (3) Hospital do Coracao; (4) Instituto do Coracao - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (5) Universidade Estadual de Campinas,; (6) Universidade de Pernambuco; (7) Pronto-Socorro Cardiologico Universitario de Pernambuco; (8) Universidade Federal do Parana; (9) Universidade Federal do Maranhao Background: There are still no studies that characterize regional differences in HFrEF in Brazil. Objective: To compare regional characteristics in the socioeconomic, clinical, and treatment aspects of HFrEF in Brazil. Methods: Rosa dos Ventos is a cohort study in all Brazilian states which will include 3,000 patients with outpatient HFrEF (EF < 50%). We carried out a cross-sectional study to compare the characteristics of patients (n = 853), according to the Brazilian region of origin: North (n = 115), Northeast (n = 351), Center-west (n = 140), Southeast (n = 77) and South (n = 170). We investigated socioeconomic characteristics, clinical presentation of HF, and use of at least four medications of guideline-directed medical therapy (GDMT) in HF (beta-blockers, mineralocorticoid antagonists, SGLT2 inhibitors, and ACE inhibitors or ARBs or ARNIs). We used Student's T and Chi-square statistical tests. Results: Comparing the patients, the youngest belonged to the southeast region (55 +- 14, p < 0.001), and were less frequently white (19%, p < 0.001) and with lower monthly familiar income (R$ 2176 +- 3015, p < 0.001) in the Northeast region. There was a higher percentage of chagasic etiology in the Central-West region (42%, p < 0.001) and of ischemic etiology in the North region (39%, p = 0.021), the latter region had the highest mean ejection fraction (37 +- 8, p < 0.001). The use of at least four GDMT drugs was more frequent in the Northeast (23%, p = 0.033) and South regions (22%, p = 0.033), with a higher frequency of ARNI use in the South (45%, p < 0.001). Conclusions: The Rosa dos Ventos Study aims to determine regional differences in HFrEF, and the results will help in planning its prevention and treatment. These preliminary data suggest regional differences in the etiology and use of therapy. 108365 Modality: Best Poster - Researcher Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION D: 14/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Comparative Effectiveness and Cost-Effectiveness of Cardioprotective Glucose-Lowering Therapies for Type 2 Diabetes in a Middle-Income Country: A Modeling Analysis ANA CLAUDIA CAVALCANTE NOGUEIRA1, Joaquim Barreto2, Beatriz Luchiari2, Isabella Bonilha2, Luiz Sergio Fernandes de Carvalho3, Andrei Carvalho Sposito2 (1) Escola Superior de Ciencias da Saude - ESCS; (2) Atherosclerosis and Vascular Biology Laboratory (Aterolab), Cardiology Division, Universidade de Campinas - UniCamp; (3) Clarity Healthcare Intelligence Background: We sought to compare the effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies in individuals with T2D in a middle-income country. Methods: A systematic search was performed for randomized clinical trials published until April 2021 reporting the incidence of MACE for pioglitazone, GLP1A, or SGLT2i. Using date from two national cohorts of T2D, we developed a Markov model to estimate the outcomes for each treatment based on incremental cost-effectiveness ratio (ICER) and the disease-adjusted life years [DALYs] gain per dollar spent projected over a lifetime horizon using a 5% annual discount rate. Results: 157 RCT including 267,508 patients and 176 active arms were considered. Compared with sulfonylureas, SGLT2i, GLP1A and pioglitazone reduced the relative risk of non-fatal MACE with HR of 0.81 (95% CI 0.69 to 0,96, p = 0.011), 0.79 (95% CI 0.67 to 0,94, p = 0.0039) and 0.73 (95% CI 0.59 to 0.91, p = 0.0057), respectively. Pioglitazone resulted in incremental effectiveness of 0.2339 DALYs per patient, at a mean incremental cost of US$1660 and a US$ 7,082 (95% CI: 4,521; 10,770) incremental cost per DALY gained, when compared to standard care. The addition of SGLT2i or GLP1A led to more evident (0.261 and 0.259, respectively) but with higher ICERs [US$ 12,061 (95% CI: 7,227; 18,121) and US$ 29,119 (95% CI: 23,811; 35,367) per DALY gained, respectively]. Compared to SGLT2i and GLP1A, pioglitazone had the highest probability of being cost-effective based on the estimated maximum willingness-to-pay threshold. Conclusions: The three therapies bear similar effectiveness in reducing cardiovascular events. In a middle-income country, pioglitazone presents a higher probability of being cost-effective followed by SGLT2i and then GLP1A. 109342 Modality: Best Poster - Researcher Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY D: 14/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Distal Transradial Access for Coronary Procedures: A Prospective Cohort of 3,991 All-Comers Patients from the Distraction Registry MARCOS DANILLO PEIXOTO OLIVEIRA1, Lelio Lemos Pinto Neto1, Ednelson Navarro2, Adriano Caixeta1 (1) Universidade Federal de Sao Paulo, UNIFESP; (2) Hospital Regional do Vale do Praiba Background: Distal transradial access (dTRA) as a refinement of the conventional transradial approach has several potential advantages in terms of patient and operator comfort, faster hemostasis, and lower risk of proximal radial artery occlusion. We aim to describe our prospective real-world experience with dTRA as default for routine coronary angiography and percutaneous coronary interventions (PCI) in a broad sample of all-comers patients. Material and methods: From February 2019 to April 2022, 3,991 consecutive all-comers patients submitted to coronary angiography and/or PCI via dTRA have been enrolled into the DISTRACTION registry. Results: Mean patient age was 63.36 +- 13.3-year-old, most male (65.4%) and with acute coronary syndromes (48,8%) at admission. Overall, 843 (20.1%) patients had non-ST-elevation myocardial infarction, 799 (20,0%) had ST-elevation myocardial infarction, and 114 (2.6%) presented in cardiogenic shock. There were only 94 (2.3%) access site crossovers, in only 79 (1.9%) patients dTRA sheath insertion could not be obtained. Right dTRA was the most frequent access (80.1%), followed by redo right dTRA (10.8%), left dTRA (8,1%) and simultaneous bilateral dTRA (0.7%). In 2,210 (60.0%) of all patients, PCI was performed and left anterior descending was the most prevalent target coronary territory (29.1%). No major adverse cardiac and cerebrovascular events and no major complications directly related to dTRA were recorded. Conclusions: The adoption of dTRA as default for routine coronary angiography and PCI in a real-world fashion of all-comers patients by experienced transradial operators appears to be feasible and safe. 111318 Modality: Best Poster - Researcher Category: DIGITAL HEALTH/INNOVATION D: 14/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Digital Personal Walking Plans Increase Physical Activity Levels of Australian Adults ELIZABETH ANNE CALLEJA1, Elizabeth A Calleja1, Dr Amanda K Buttery1, Teresa Gadaleta1, Sheree Hughes1, Jarrod Leggett1, Associate Professor Trevor Shilton1 (1) National Heart Foundation of Australia Physical activity is an important modifiable risk factor for the prevention and management of cardiovascular disease and can reduce the risk of morbidity by 35% . However, only 15% of Australian adults meet the physical activity guidelines . A national walking program was rolled out across Australia led by a national voluntary group-based community walking program in 2007. In response to the COVID-19 pandemic, we aimed to develop a digital program option for people to walk independently. Personal Walking Plans (PWP) were launched in Australia as a free six-week web-based digital program for adults to address this need. Methods: We designed personal walking plans on behaviour change principles and theory. This included four graded walking programs with strengthening and flexibility exercises, supported with online instructional videos and motivational messaging via email or text (SMS) messages. A digital self-report survey was conducted on enrollment to the program, and after completion at six weeks. These were completed between 11th of May and 30th June 2021. Survey questions included established items on participant goals, physical activity levels, influence of motivational messaging (text and email) and intention to continue walking following program completion. Results: Of 2338 (mean 65 years; 87% female) participants completing the survey, 74% completed the program. Of these, 86% achieved their goal and 69% met the Australian physical activity guidelines by the end of the six-weeks. On average, participants increased the number of days they engaged in physical activity from 2.7 days to 4.4 days per week by the end of the six weeks. Strength exercise sessions increased from 0.9 days to 2.4 days per week. Participants reporting they paid attention to motivational messages increased their physical activity (30min physical activity, 4.4 days, strength 2.4 days) more than those who ignored/did not receive texts (30min physical activity, 3.9 days, strength 2.0 days). Nearly all (99%) reported that they would continue walking following the intervention. Conclusion: A six-week digital personal walking plan was effective in improving participants' attainment of the Australian adult physical activity guidelines. Motivational text messaging and emails appeared to enhance engagement with the program and physical activity levels. Long-term follow-up surveys at 6 and 12 months will evaluate if benefits are sustained over time. 111421 Modality: Best Poster - Researcher Category: CARDIOVASCULAR IMAGING D: 14/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Myocardial Blood Flow Reserve by CZT Gamma Camera Increases Accuracy of Obstructive Coronary Artery Disease Detection RONALDO DE SOUZA LEAO LIMA1, Andre Luiz Bezerra2, Claudio Domenico2, Andrea Rocha de Lorenzo2 (1) Fonte Imagem; (2) Universidade Federal do Rio de Janeiro Introduction: CZT cameras have higher sensitivity for photon detection, as well as higher temporal and spatial resolution. These have enabled que noninvasive quantification of myocardial flow reserve (MFR), which may increase the accuracy of myocardial perfusion SPECT (MPS) for the detection of obstructive coronary artery disease (CAD). This study aimed to compare the accuracy of CZT MPS and of MFR for the detection of obstructive CAD. Methods: 66 patients with CAD (>50% obstruction) detected at invasive coronary angiography or CT angiography underwent dipyridamole MPS and MFR evaluation within 30 days. A 1-day protocol (rest-stress) was used to quantify MFR. The acquisition of dynamic rest and stress images was initiated simultaneously to 99mTc sestamibi injection (10mCi e 30mCi, respectively), both lasting for 11 minutes, followed by 5-minute imaging. Pharmacologic stress with dipyridamole (0,56 mg/kg for 4 minutes) was performed with the patient positioned in the CZT camera. The images were processed and time-activity curves were generated, calculating global and regional MFR in a semiautomatic software. A global or regional MFR <2.0 was considered abnormal. The MPS perfusion images were classified as normal or abnormal and perfusion scores were calculated. The images were interpreted by experienced physicians blinded to the results of MFR and coronary angiography/CT. Results: Mean age of the population was 63 +- 3 years, 51.5% male. Hypertension, hypercholesterolemia and diabetes were the most frequente risk factors (80.3%, 45.4%, and 42.4%, respectively). Thirty patients (45.5%) had single-vessel CAD, 28 (42.4%) 2-vessel CAD and 8 (12.1%), triple-vessel CAD. Among the 110 vessels with obstruction, 67 had perfusion abnormalities in MPS and 81 had reduced MFR, while among the normal vessels, 76 had normal MPS and 74 had preserved MFR. The sensitivity of MFR (73,6%) was higher than that of MPS (60.2%), without significant changes in specificity (86,4 vs 84.1%). Conclusions: MFR in the CZT camera is an absolute, physiologic, quantifiable measure which is more sensitive for the detection of obstructive CAD than perfusion abnormalities in MPS, especially in patients with multivessel CAD. 111997 Modality: Best Poster - Researcher Category: COVID-19 AND CARDIOVASCULAR SYSTEM D: 14/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Predictors of Venous Thromboembolism in COVID-19 Patients: Results of the COVID-19 Brazilian Registry WARLEY CEZAR DA SILVEIRA1, Manuela Furtado Sacioto2, Luiza Margoto Marques2, Mateus Chaves Ferreira1, Beatriz Figueiredo Lima1, Maria Izabel Alcantara Cunha4, Bruno Barbosa Miranda de Paiva1, Marcos Andre Goncalves1, Polianna Delfino Pereira1, Ana Beatriz de Castro Feres2, Magda Carvalho Pires1, Milena Soriano Marcolino1 (1) Universidade Federal de Minas Gerais (UFMG); (2) Faculdade Ciencias Medicas de Minas Gerais (FCMMG); (3) Institute for Health Technology Assessment (IATS/CNPq); (4) Centro universitario de Belo Horizonte (UNIBH) Introduction: COVID-19 patients present a high incidence of venous thromboembolism (VTE), which requires early recognition and treatment. In those patients, the diagnosis of pulmonary embolism is a challenge, as its symptoms and signs overlap with the ones of the severe acute respiratory syndrome (SARS). Several studies have tried to identify risk factors of VTE in hospitalized COVID-19 patients, as a path to promote prevention, early diagnosis and treatment. However, such studies have shown inconsistent results. Objective: To identify VTE predictors by both logistic regression (LR) and machine learning (ML) approaches and report the incidence of thromboembolic complications in COVID-19 and their prognostic impact. Methods: This substudy of a large Brazilian COVID-19 Registry included consecutive COVID-19 adult patients from 16 hospitals, admitted between March and September, 2020. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting and bagging were used to investigate the association of variables upon hospital presentation with VTE. Results: Among 4,120 patients (median age was 61 years [IQR, 48-72] years-old, 55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95%CI 1.11-2.02); being an ex-smoker (OR 1.44, 95%CI 1.03-2.01); surgery <=90 days (OR 2.20, 95%CI 1.14-4.23); axillary temperature (OR 1.41, 95%CI 1.22-1.63); D-dimer >=4 times above the upper limit of reference value (OR 2.16, 95%CI 1.26-3.67), lactate (OR 1.10, 95%CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95%CI 1.005-1.075) were independent predictors of VTE. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. Patients with confirmed VTE had higher mortality (28.4% vs 18.5%, p < 0.001) and had a higher frequency of mechanical ventilation support (58.4% vs 26.4%, p < 0.001) and renal replacement therapy (21.5% vs 9.7%, p < 0.001), when compared to the group without confirmed VTE. Conclusion: By using ML and LR analysis, we showed that D-dimer, axillary temperature, neutrophil count, CPR and lactate levels are risk factors for VTE in COVID-19 patients. Therefore, we suggest that patients presenting these risk factors at admission should be more closely monitored for VTE development, considering the importance of prevention, early diagnosis and treatment of VTE. 108390 Modality: Best Poster - Young Researcher Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE D: 14/10/2022 H: 16:10/16:50 L: Area de exposicao de posteres Doxorubicin-Induced Cardiotoxicity Attenuation by Omega-3 Fatty Acid Supplementation in Rats is not Mediated by Sphingomyelin-Ceramide Pathway MARINA GAIATO MONTE 1, Carolina Rodrigues Tonon1, Anderson Seiji Soares Fujimori1, Ana Paula Dantas Ribeiro1, Katashi Okoshi1, Paula Schmidt Azevedo1, Marcos Ferreira Minicucci1, Leonardo Antonio Mamede Zornoff1, Sergio Alberto Rupp de Paiva1, Bertha Furlan Polegato1 (1) Faculdade de Medicina de Botucatu Introduction: Doxorubicin (DOX) is widely used effective chemotherapy drug; however, it can cause cardiotoxicity which is a very serious side effect. There is no effective therapy for cardiotoxicity. Omega-3 fatty acid (O3) supplementation may act in the sphingomyelin-ceramide pathway. We aimed to evaluate the influence of O3 in attenuating DOX-induced cardiotoxicity. Methods: Male Wistar rats (n = 60) were divided into 4 groups: control (C), administration of O3 only (O3), DOX only (D), and DOX and O3 (DO3). O3 (400 mg/kg/day, gavage) was administered for 6 weeks. DOX (3.5 mg/kg, IP, once a week) was administered for the last 4 weeks of the experiment. At the end of 6 weeks, rats were submitted to echocardiogram and euthanized (thiopental 120 mg/kg, ip). Statistical analysis: 2-way ANOVA (pi: p value for the interaction between DOX and O3; pD: p value for the effect of DOX; pO3: p value for the effect of O3). Results: Group D exhibited increased left atrium diameter/aorta diameter ratio (C 1.31 +- 0.11; D 1.45 +- 0.11; O3 1.36 +- 0.11; DO3 1.27 +- 0.11; pD = 0.467, pO3 = 0.028, pi < 0.001) and decreased left ventricular fractional shortening (C 0.57 +- 0.07; D 0.46 +- 0.07; O3 0.56 +- 0.08; DO3 0.53 +- 0.08; pD = 0.002; pO3 = 0.164; pi = 0.046) compared to Group C, characterizing diastolic and systolic dysfunction, respectively. DOX increased neutral sphingomyelinase activity (nSMase, C 2283 +- 412; D 2879 +- 680; O3 2461 +- 639; DO3 3319 +- 284 UI fluorescence; pD < 0.001, pO3 = 0.087, pi = 0.461) and decreased myocardial nSMase protein quantification (C 0.05 +- 0.03; D 0.04 +- 0.02; O3 0.05 +- 0.02; DO3 0.03 +- 0.02 arbitrary units; pD = 0.009, pO3 = 0.455, pi = 0.275). There were no differences between groups in myocardial ceramide deposition evaluated by immunohistochemistry. Conclusion: O3 supplementation attenuates DOX-induced diastolic and systolic dysfunction with no changes in neutral sphingomyelinase activity or expression in the myocardium. Financial support: FAPESP 2018/25677-7 and CNPq 407201/2021-1. 108392 Modality: Best Poster - Young Researcher Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE D: 14/10/2022 H: 16:10/16:50 L: Area de exposicao de posteres Netosis is Involved in the Pathophysiology of Acute Doxorubicin-Induced Cardiotoxicity MARINA GAIATO MONTE 1, Carolina Rodrigues Tonon1, Tatiana Fernanda Bachiega Pinelli1, Anderson Seiji Soares Fujimori1, Ana Paula Dantas Ribeiro1, Nayane Maria Vieira1, Natalia Fernanda Ferreira1, Danilo Malmonge Barbosa Luciano1, Ronny Peterson Cabral1, Katashi Okoshi1, Bertha Furlan Polegato1, Leonardo Antonio Mamede Zornoff1 (1) Faculdade de Medicina de Botucatu Background: Doxorubicin (dox) is used in the treatment of several types of cancer. However, cardiotoxicity is a common side effect of the drug. The pathophysiology of cardiotoxicity is not clearly understood. Neutrophils produce attractant substances such as NETs (neutrophil extracellular traps), that are involved in immune response and inflammation which could mediate myocardial extracellular matrix remodeling. Purposes: To analyze the role of NETs in the pathophysiology of acute dox-induced cardiotoxicity. Methods: 60 male Wistar rats were allocated into 3 groups: Control (C), Dox (D), and Dox + DNAse (DD). D and DD groups received an intraperitoneal injection of dox 10 mg/kg, and 2h later, DD received a subcutaneous injection of DNAse 20 mg/kg (NETs inhibitor). Rats were submitted to cardiac function evaluation and euthanasia 48h after dox injection. Statistical analysis: one-way ANOVA. Results: D showed increased NETs production compared with C and DD (C = 2997 +- 810; D = 5955 +- 1906; DD = 4108 +- 1674 pg/mL; p < 0.001). Transthoracic echocardiogram showed no differences in systolic parameters, but isovolumetric relaxation time corrected by heart rate was higher in D and DD than C (C = 46 +- 4.6; D = 51 +- 7.9; DD = 51 +- 7.7, p = 0.039). Additionally, in isolated heart study, area under curve for diastolic pressure-volume ratio was reduced in D, indicating lower ventricular compliance, compared with C and DD (C = 827 +- 74; D = 670 +- 109; DD = 966 +- 218; p = 0.007). Dox induced increased malondialdehyde myocardial concentration in D and DD compared to C (C = 48 +- 28; D = 73 +- 32; DD = 82 +- 25 nmol/mg of protein; p < 0.05). Regarding extracellular matrix, dox increased and DNAse attenuated collagen in cardiac tissue (C = 2.88 +- 0.97, D = 3.51 +- 0.7, DD = 2.99 +- 0.66%; p < 0.05). Additionally, dox increased matrix metalloproteinase activity (MMP)-2 (C = 1.01 +- 0.28, D = 2.04 +- 0.47, DD = 2.36 +- 0.6; p < 0.001), but DNAse did not interfere with this parameter. Evaluation of protein expression of |Type 2 and 4 MMP tissue inhibitors (TIMP) showed no differences between groups. Conclusions: Dox-induced cardiotoxicity is associated with diastolic dysfunction, cardiac fibrosis, increased MMP-2 activity, and oxidative stress. NETs are involved in the pathophysiology of dox-induced cardiotoxicity. Netosis inhibition improved diastolic function, associated with decreased myocardial collagen content. However, this effect was not mediated by oxidative stress, MMP-2 activation, or TIMP-2 and -4 protein expression. 109335 Modality: Best Poster - Young Researcher Category: CARDIO-ONCOLOGY D: 14/10/2022 H: 16:10/16:50 L: Area de exposicao de posteres Resistance Training Preserves Left Ventricle Ultrastructure and Function in Doxorubicin-Induced Cardiotoxicity RENATA ALVES1, Claudia de Morais Sequeira1, Jefferson Fernandes Evangelista1, Ana Lucia Rosa Nascimento1, Cristiane Matsuura1 (1) Universidade do Estado do Rio de Janeiro Introduction/aim: It is well known that doxorubicin (DOX) elicits toxic effects on the heart limiting its use in cancer treatment. Here, we investigated the effects of resistance training on left ventricle (LV) ultrastructure and function in DOX-induced cardiotoxicity in rodents. Methods: Male adults Sprague Dawley rats were divided into three groups (n = 10): control, DOX that remained sedentary (DoxSed), or DOX submitted to resistance training (DoxTr). Resistance training (5 d/wk for 8 wks) consisted of climbing a ladder with weights placed on the tail, with progressive increase in the training load (number of repetitions and weight). DOX was administered for 10 consecutive days (1 mg/kg/d, i.p.) and it initiated concomitantly with training. At the end, cardiac function was measured by echocardiography, and LV fragments were processed for transmission electron microscopy. Results: There was a reduction in mortality in DoxTr compared to DoxSed (20 vs. 38%, P < 0.001, log rank test). The decrease in LV ejection fraction observed in DoxSed was attenuated in DoxTr (control: 76 +- 1; DoxSed: 64 +- 1; DoxTr: 71 +- 1%; P < 0.05, one-way ANOVA). The most striking effects were seen in LV ultrastructure (Fig 1). The control group showed a normal structural arrangement, with myofibrils arranged in parallel, preserved sarcomeres with uniform distance between Z lines. Intact mitochondria were seen in parallel arrangement to the myofibrils. The cardiomyocytes of the DoxSed group showed severe cellular disruption, with fragmentation of the myofibrils, disappearance of some sarcomeres, increased electron-lucid cytoplasmic content and the presence of autophagosomes, and degenerated mitochondria. Resistance training resulted in positive effects on the ultrastructural morphology of cardiomyocytes, with intact mitochondria and large areas of preservation of the structural organization of the sarcomere, although it was still possible to observe a non-linear arrangement and reduction in the density of myofibrils. Conclusion: Resistance training can be a non-pharmacological strategy to prevent the deleterious effects of DOX on the heart. 110132 Modality: Best Poster - Young Researcher Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION D: 14/10/2022 H: 16:10/16:50 L: Area de exposicao de posteres Physiological Electrocardiographic Findings in a Brazilian Cohort of Young Football Players: B-Pro Foot Ecg Pilot Study FILIPE FERRARI1, Henrique C. da Silva2, Luiz G. M. Emed3, Guilherme D. Dilda4, Haroldo C. Aleixo5, Marcio Dornelles6, Fernando Bassan7, Felipe E. F. Guerra8, Frederico P. L. Coimbra9, Mateus F. Teixeira10, Anderson D. da Silveira11, Ricardo Stein1 (1) Hospital de Clinicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brazil; (2) Universidade do Estado do Para (UEPA), Belem, PA - Brazil; (3) Hospital Cardiologico Costantini, Curitiba, PR - Brazil; (4) Hospital das Clinicas da Universidade de Sao Paulo (USP), Sao Paulo, SP - Brazil; (5) Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG - Brazil; (6) Gremio Foot-Ball Porto-Alegrense (GFPA), Porto Alegre, RS - Brazil; (7) Universidade do Estado do Rio de Janeiro (UERJ), RJ - Brazil; (8) Clinica Biocardio, Natal, RN - Brazil; (9) Hospital de Urgencias de Goiania, Goiania, GO - Brazil; (10) Clube de Regatas Vasco da Gama, RJ - Brazil; (11) Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS - Brazil Introduction: The 12-lead ECG is a useful tool for screening cardiac abnormalities in athletes. We aimed to describe physiological ECG findings in young Brazilian football players (YBFP) based on the "2017 International Criteria for Electrocardiographic Interpretation in Athletes". Methods: Cross-sectional/descriptive study. Intra-group differences were estimated by linear models or binomial and multinomial logistic regressions. Results: 3.490 YBFP from 41 clubs, aged 15-35 years (median: 19 y) were evaluated. 1.668 were Caucasians, 1.154 Mixed-race (MR) and 668 Afro-Brazilians (AB). Prevalence: sinus bradycardia (50%), incomplete RBBB (12%), first-degree AV block (3%), Mobitz type I AV block (0.1%), and increase QRS voltage for left or right ventricular hypertrophy (34% and 15%, respectively). ST-elevation followed by T-wave inversion confined to V1-V4 leads were identified in 2% of AB. Early repolarization (ER) was present in 35% of athletes (AB versus Caucasians and MR: P = 0.002 and P = 0.004, respectively), which was similar to the PR interval (P < 0,001 for both comparisons). There was no difference between Caucasians and MR for ER or PR intervals. For all remaining variables, there was no difference among races. Conclusions: This is the first large study to describe the prevalence of physiological electrocardiographic findings in YBFP. Further studies comparing the frequency of these findings with the prevalence observed in other cohorts are welcome. 112183 Modality: Best Poster - Young Researcher Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT D: 14/10/2022 H: 16:10/16:50 L: Area de exposicao de posteres Improving Prognostic Assessment in Heart Failure: The Interplay between Nyha Classification and Cardiopulmonary Exercise Testing PEDRO HENRIQUE DE BORBA ENGSTER1, Pedro Henrique de Borba Engster1, Andre Zimerman1, Anderson Donelli da Silveira1, Marina S. Borges1, Thomas U. Schaan1, Gabriel C. de Souza1, Giovanni Donelli Costa1, Luis Eduardo Rohde1 (1) Hospital de Clinicas de Porto Alegre; (2) Universidade Federal do Rio Grande do Sul Background: For patients with heart failure (HF), the validity of the New York Heart Association (NYHA) functional class to assess prognosis may be limited when compared with the objective cardiopulmonary exercise test (CPET). Purpose: To investigate the prognostic value of NYHA classification and CPET parameters. Methods: We included the first CPET of every adult patient with HF who in a tertiary care center in Brazil. NYHA class was determined on the day of CPET or during the prior ambulatory visit. NYHA and Weber classes were stratified into "favorable" (NYHA I or II; Weber A or B) or "poor" (NYHA III or IV; Weber C or D), and subjects with discordant classes were compared in a survival analysis. Primary endpoint was all-cause mortality at 5 years. We used a Cox proportional hazards model to estimate the probability of death in 5 years according to relative peak VO2 and NYHA class, adjusted for age and sex. Results: We included 855 patients, of which 30% (255) were classified as NYHA I, 43% (368) as NYHA II, 24% (202) as NYHA III, and 4% (30) as NYHA IV. Mean age was 56 years (+-13), 42% (359) were female, and mean LVEF was 36% (+-15). Mean relative peak VO2 ranged from 19.6 (NYHA I) to 14.0 (NYHA IV) ml/kg/min. Patients with poor NYHA and favorable Weber classes displayed similar rates of all-cause mortality as patients with favorable NYHA and poor Weber classes . The distinction between NYHA I and II did not, however, improve prognostic assessment. Conclusions: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information, and NYHA classification may be particularly limited for mild cases of HF. These findings question the use of NYHA as the main determinant to guide HF therapy. 108597 Modality: Best Poster - Scientific Initiation Category: DIGITAL HEALTH/INNOVATION D: 13/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Prediction Factors for Events in the Remote Monitoring of Implantable Electronic Cardiac Devices. Not for all, but Essential to Many! MARIA EDUARDA QUIDUTE ARRAIS ROCHA1, Bruna Sobreira Kubrusly2, Fernanda Pimentel Arraes Maia2, Rodrigo Carvalho Paiva3, Alessia de Alencar Araripe Gurgel3, Davi Sales Pereira Gondim1, Juvencio Santos Nobre2, Luis Gustavo Bastos Pinho2, Ana Gabriela Ponte Farias2, Maria Camila Timbo Rocha3, Eduardo Augusto Quidute Arrais Rocha3, Francisca Tatiana Moreira Pereira2 (1) Universidade de Fortaleza (Unifor); (2) Universidade Federal do Ceara (UFC); (3) Centro Universitario Christus (UNICHRISTUS) Introduction: The remote monitoring (RM) of implantable electronic cardiac devices (IECD) has shown advantages in the reduction of morbidity and mortality. The early detection of alterations and the possibility of treatment before the occurrence of symptoms has been a great attractive of this follow-up method. Meanwhile, not all the groups benefit, there are costs associated to these devices and the large number of events may determine an overload to the professionals. This work aimed to identify the predictive factors of larger benefit during the IECD follow-up through RM. Methods: This is a cohort prospective study. The statistical analysis used logistic regression models, with p < 5% for statistical significance. The explanatory variables were selected by a stepwise selection method based on the Akaike Information criterion as a measure to choose the best explaining model. The analyzed variables were age, sex, functional class (FC) >= II, ejection fraction (EF), type of IECD, sustained ventricular tachycardia and red alert transmission, indicating important events detections. Three different models were created, with the response variable given by, respectively, elective therapy change (model 1), urgent therapy change (model 2) and whether event detections prevented hospitalizations (model 3). Results: There were 119 patients, with mean age of 72 +- 14 years, 69.8% males. The most common pathologies were ischemic cardiomyopathy 28.6%, dilated cardiomyopathy 22.7% and Chagas disease 6.7%. The groups using a biventricular pacemaker(PM) (75.0%, p = 0.02), reduced EF (76.5%, p = 0.01) FC >= Il (75.0%, p < 0.01) had the larger rates of events. The red alert transmission variable was statistically significant in the three models (p-values of, respectively, 0.048;0.007 and 0.048), while the presence of ventricular tachycardia was statistically significant in two models, with p-vales of p = 0.039 (changes in elective therapy) and p = 0.039 (prevented hospitalizations). The FC >= II was associated to the urgent therapy change (p = 0.047). Conclusion: Patients with biventricular PM, reduced EF, and more advanced FC had higher event rates in the RM of IECD. The detection of alerts considered by the system as important (red alerts) was associated with changes in immediate, elective conduct and was able to reduce hospitalizations. 109148 Modality: Best Poster - Scientific Initiation Category: HYPERTENSION/RENAL DENERVATION D: 13/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Inflammatory Markers and Chronic Kidney Disease JOAO GABRIELL BEZERRA DA SILVA1, Joao Gabriell Bezerra da Silva1, Gabriela da Silva Nascimento1, Hugo Farah Affonso Alves1, Lucca Hiroshi de Sa Kimura1, Joao Gabriel Rega do Nascimento Vallaperde1, Vitor de Melo Nolasco1, Bianca Botelho Viegas1, Carlos Filipe dos Santos Pimenta1, Bernardo Chedier1, Arthur Fernandes Cortez1, Elizabeth Silaid Muxfeldt1 (1) Universidade Federal do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho - ProHArt Background: Resistant hypertension (RHT) defined as an uncontrolled blood pressure (BP) despite the use of 3 or more antihypertensives presents a high cardiovascular (CV) morbidity and mortality and high prevalence of chronic kidney disease (CKD). High BP levels and kidney injury appear to be strongly associated with inflammatory biomarkers. Objective: To evaluate the relationship between inflammatory markers and subclinical and established CKD in a large cohort of patients with RHT. Methods: Cross-sectional study that evaluated 423 resistant hypertensives (30.5% male, mean age 64.0 +- 10.8 years) submitted to renal function assessment (albuminuria dosage and evaluation of glomerular filtration rate calculated from the CKD-EPI formula) and dosage of inflammatory markers: TNF-alpha, MCP-1, E-selectin and PAI-1. Socio-demographic characteristics, anthropometric measurements and CV risk factors were recorded. We considered subclinical CKD those patients with moderately high albuminuria (30-300 mg/g) and/or GFR between 30 and 60 ml/min/1.73 m2 and established CKD those who presented albuminuria >300 mg/g and/or TFG < 30 ml/min/1.73 m2. Variance analysis compared serum levels of the 4 inflammatory markers and bivariate analysis compared patients with and without subclinical and established chronic kidney disease. Results: The prevalence of established CKD was 7.3% (31 patients) and subclinical CKD was 47% (187 patients). Patients with subclinical CKD were older and with higher arterial stiffness (higher pulse wave velocity). TNF-alpha (7.1 [4.4-8.6] vs 51, [3.2-7.5]) and MCP-1(284 [220-379] vs 260 [185-359] were significant higher in this group of patients. When we analyzed patients with established CKD, we observed that they have higher BP levels and that TNF-alpha values (7.8 [5.6-14.0] vs 5.6 [3.5-8.3]) and E-selectin (54.4[41.2-61.3] vs. 47.8 [32.0-65.3]) were significantly higher in this group. Conclusion: Among the inflammatory markers evaluated, which was most strongly correlated with subclinical CKD were TNF-alpha and MCP-1, while those with established CKD have higher TNF-alpha and E-selectin levels, possibly pointing out that the MCP-1 is an earlier marker of kidney injury. 111855 Modality: Best Poster - Scientific Initiation Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH D: 13/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Mortality from Cardiovascular Diseases and Policies to Reduce Salt Consumption in South American Countries: An Ecological Study LUIZ FELIPE FACANHA RAMOS1, Hildeman Dias da Costa2, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia Introduction: Mortality from cardiovascular diseases (CVD) is aggravated by arterial hypertension, as a consequence of high consumption of table salt. Worldwide salt intake is above the 5 grams (2 grams of sodium) per day recommended by the World Health Organization (WHO), and its consumption varies from 8.5 to 15 grams per person. Objective: To relate CVD mortality with policies to reduce salt/sodium consumption in South American countries in the year 2019. Methodology: This is an analytical ecological study of geographic distribution with secondary data from the Information Platform in Health for the Americas (PLISA), from the Pan American Health Organization, of the year 2019, with CVD mortality indicators and policies to reduce salt/sodium consumption in South American countries. In addition, mortality rates (MT) were standardized per 100,000 inhabitants, with a confidence interval of 95%, classified by quintile. These data were tabulated in the Microsoft Excel software and the variables were analyzed in the GNU SPPP software version 1.5.3, using the Pearson Correlation Test, with a significance level of 5%. Results: In 2019, in South America, the highest CVD mortality rates occurred in Guyana (TM = 448.3; 95% CI 363.3-548.5; Q5) and Suriname (TM = 270.8; 95% CI 212.1-337.6; Q5), on the other hand, the lowest mortality occurred in Peru (TM = 77.8; 95% CI 56.9-103.9; Q1) and in Chile (TM = 95. 5; 95% CI 74.4-118.9; Q1). It is noteworthy that the countries that had the highest mortality are the nations that did not have any (n = 0) initiative to reduce salt/sodium consumption in 2019, however, the countries with the lowest mortality were those that developed 3 policies to reduce this excessive consumption. It is evident that Brazil developed 2 reduction policies, but had a high number of deaths from CVD (TM = 217.1; 95% CI 189.9-239.9; Q3). Analyzing the bivariate correlation of the two variables, a negative Pearson coefficient was obtained (r = -0.59; p = 0.043). Conclusion: Countries that developed more initiatives to reduce excessive salt consumption had significantly lower mortality rates from CVD, showing the importance of reducing this consumption to avoid hypertensive complications that lead to death. Thus, the inversely proportional relationship between the number of these policies and the number of deaths from CVD is confirmed. 111704 Modality: Best Poster - Scientific Initiation Category: CARDIOVASCULAR PHARMACOLOGY D: 13/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Cardiovascular Outcomes in Long-Term with Prasugrel Versus Clopidogrel in Acute Coronary Syndromes: Real-World and Paired Analysis for Propensity Score PIETRA ARISSA COELHO MATSUNAGA1, Evellyn Cristiny Pereira Marinho Bezerra1, Julia Fonseca da Silva Saad1, Lara da Silva Soledade1, Ana Claudia Cavalcante Nogueira3, Alexandre Anderson de Souza Munhoz Soares3, Gustavo Alexim2, Luiz Sergio Fernandes de Carvalho5, Renato Barros4 (1) Universidade Catolica de Brasilia UCB; (2) Hospital de Base do Distrito Federal HB-DF; (3) Instituto Aramari Apo; (4) Hospital Regional de Sobradinho do Distrito Federal HRS-DF; (5) Clarity Healthcare Intelligence Introduction: Prasugrel is an thienopyridine antiplatelet agent, which can be an important alternative to clopidogrel in patients with Acute Coronary Syndrome (ACS) treated through percutaneous coronary intervention. In spite of the role of clopidogrel in these conditions, there are no long-term real-world studies comparing clopidogrel versus prasugrel. Objective: To evaluate the long-term risk of major adverse cardiovascular events (MACE) in patients with ACS who are making use of prasugrel or clopidogrel. Methods: This study is a retrospective analysis of all the individuals that were admitted with the principal diagnosis of acute coronary syndrome within the period of 2013 to 2015 and were submitted to cardiac catheterization in public hospitals of Brasilia, FD, Brazil. The total group was divided into two: the first group being of patients who took clopidogrel and the second group formed by patients on prasugrel. The primary clinical outcome was comprised by cardiovascular (CV) deaths and recurrent ACS (MACE). Multivariate analyses on 16 covariates were carried and followed by a Propensity Score Matching analysis (PSM). Results: A total of 2,491 patients with a principal diagnosis of ACS were included (1,616 with clopidogrel and 875 with prasugrel) and monitored for a median of 6.5 (IQR 1.9) years with 742 primary events. Clopidogrel was associated with high rates of MACE in 12 months (20.1% vs 11.8%, p < 0.001, 428 MACE) and 24 months (23.8% vs 17.7%, p < 0.001, 540 MACE) compared to prasugrel, but the curves equalized at 36 months (25.9% vs 26.6%, p = 0.740) and remained equalized until median follow-up time. In multivariate analysis, prasugrel showed a hazard ratio (HR) 0.61 (95% CI 0.47-0.78 at 12 months), 0.78 (95% CI 0.63-0.96, p < 0.001 at 24 months) and 0.94 (95% CI 0.78-1.1 at 36 months). The results were maintained in the PSM analysis. The mean time on prasugrel in this cohort was 22.1 (IQR 5.9) months. Conclusion: Stemming from these findings, despite the already known role that prasugrel has in reducing the risk of MACE in ACS, these results do not seem to be sustained in the long term. The data reveal that after the interruption of drug use there was an increase in the amount of major adverse cardiovascular events in the second and third year of monitored patients in the prasugrel group. Therefore, the benefit of using prasugrel is neutralized over time. 111863 Modality: Best Poster - Scientific Initiation Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE D: 13/10/2022 H: 10:00/10:40 L: Area de exposicao de posteres Is a Non-Invasive Method for ECG And HRV Assessment Capable to Detect Ventricular Dysfunction and Sympathetic Denervation? RAFAEL DIAS DE BRITO OLIVEIRA1, Denise Mayumi Tanaka2, Thayrine Rosa Damasceno1, Camila Godoy Fabricio2, Alessandra Arantes Resende2, Eduardo Elias Vieira de Carvalho2, Dawit Albieiro Pinheiro Goncalves1, Enrico de Francisco Magnani1, Mariana Duarte de Souza1, Marcus Vinicius Simoes2, Luciano Fonseca Lemos de Oliveira1 (1) Universidade Federal de Minas Gerais - UFMG; (2) Faculdade de Medicina de Ribeirao Preto - FMRP/USP Introduction: Denervation of atrial parasympathetic and ventricular sympathetic fibers is common in chronic Chagas cardiomyopathy (CC) and may be associated with increased ventricular arrhythmias and sudden death. However, it is unclear if the heart rate variability (HRV) present potential to detect these alterations. Objective: We aimed to evaluate the applicability of a low-cost, non-invasive, and unrestricted method to identify animals with ventricular sympathetic denervation and severe cardiac dysfunction in an experimental model of CC in hamsters. Methods: In the study's first phase, 10 control hamsters were used to validate the non-invasive electrocardiogram (ECG) acquisition system using a vest. Signal quality and heart rate variation were evaluated in anesthetized and dobutamine-infused animals. The vest was also compared to the acquisition of invasive electrodes in conscious animals. In the second phase, HRV was analyzed in an experimental model of CC (CC; n = 6) and its respective controls (CT; n = 6). Myocardial function and morphology were evaluated by two-dimensional echocardiography in dedicated equipment (VEVO2100). The intensity of ventricular fibrosis and/or inflammation was assessed by the extent of perfusion defects at rest using high-resolution myocardial perfusion scintigraphy, acquired by locally constructed equipment and validated system of small animal images. Results: The ECG acquired by the vest showed excellent signal quality, detecting both the increase in HR during dobutamine infusion and HRV in awake animals. In CC animals, left ventricular ejection fraction (LVEF) correlated with indicators of parasympathetic activity (LF; r = 0.72, p = 0.01) and sympathetic activity (HF; r = -0.72, p = 0.01), as well as with the LF/HF ratio (r = 0.70, p = 0.01). In addition, a significant correlation was observed between left ventricular perfusion defect (LVPD) with LF (r = 0.72, p < 0.00), HF (r = -0.72, p < 0.00), and LF/HF (r = 0.71, p = 0.01). A significant correlation was also observed between left ventricular diastolic diameter (LVDD) and LF (r = 0.59, p = 0.04) and HF (r = -0.59, p = 0.04). Conclusion: The low-cost, non-invasive and unrestricted vest method effectively detected ECG signals from animals at rest, during dobutamine infusion and in motion. The vest was also able to detect autonomic changes resulting from ventricular dysfunction, and was sensitive in identifying sympathetic denervation resulting from myocardial fibrosis and/or inflammation. 107748 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Focus Echocardiography for Prediction of Adverse Intrahospital Outcomes of Acute Pulmonary Thromboembolism in COVID-19 Pandemic - Single Center Experience IRENA MITEVSKA1, Elena Grueva1, Irina Kotlar1, Emilija Lazarova1, Marijan Bosevski1 (1) University Cardiology Clinic Introduction: In patients with pulmonary embolism (PE), assessment of right ventricular (RV) function on transthoracic echocardiography has been shown to be an independent predictor of 30-day mortality. Objective: We wanted to assess how echocardiographic assessment for RV function compares with other PE prognostic parameters used in ICU during the COVID-19 pandemic. Methods: This is retrospective cohort study of patients with confirmed PE hospitalized in Intensive Care Unit between January and December 2020. All unstable patients underwent 2-dimensional FOCUS echocardiography before CT pulmonary angiography (CTPA). FOCUS included assessment for right ventricular dilation, McConnell's sign, septal flattening, tricuspid regurgitation, and tricuspid annular plane systolic excursion (TAPSE). Adverse outcomes were defined as shock, respiratory failure requiring intubation, death, or major bleeding. We have evaluated FOCUS markers of PE diagnosis and prognosis, as well as independent ICU mortality predictors. Results: We studied 47 patients, with mean age 58.6 +- 19.4 years. Eight patients (17%) had massive PE (3 patients positive for COVID-19) and 39 (83%) had sub massive PE confirmed by CTPA. Twelve patients (25,5%) were tested for COVID 19 with PCR assay, and 3 come positive (12.5%). Eight patients were high risk with shock (17%), 29 were intermediate high risk (61.7%) and 10 patients were intermediate low risk (21.3%). Abnormal RV function with TAPSE <17 was found in 32 patients (68%). Five high risk patients died within 72 hours, resulting in an overall ICU mortality rate of 10,6% and 62.5% for patients with cardiogenic shock. We found FOCUS echocardiography 93% (95% confidence interval [CI] = 72% to 98%) sensitive and 69% specific (95% CI = 55% to 81%) for PE. Mean TAPSE values in patients who died were 13+-/2, comparing to 18+/-2, p < 0.001 in survivals. Multivariate logistic regression analysis showed thrombolytic therapy OR 2.145 (95% CI: 1.105-4,512), TAPSE <14 OR 2.893 (95% CI: 0.932-3.241), and acute renal failure OR 1.821 (95% CI: 1.105-4.762) as an independent mortality predictors. Conclusions: RV dysfunction is significant predictor of intrahospital adverse PE outcomes. A negative FOCUS examination significantly lowers the likelihood of PE in most unstable patients. Focus echocardiography is very useful tool for fast assessment of RV function, risk stratification and PE management decision in unstable patients during the COVID-19 pandemic. 107749 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Effects of a Mountain Ultramarathon on Biochemical Markers of Myocardial Damage and Ventricular Dysfunction in Young and Inexperienced Runners, Unaccustomed to Altitude ROQUE DANIEL GONZALEZ1, Cayetano Bellomio2, Mercedes Rios2, Carlos Ramiro Castellanos1, Manuel Parajon Viscido2, Roque Daniel Gonzalez1 (1) Instituto de Cardiologia Tucuman; (2) Sociedad Tucumana de Medicina del Deporte It has been reported that ultramarathons can elevate plasmatic levels of troponins and natriuretic peptides. The mechanisms and significance of these findings is debated. The objective of this study was to investigate the behavior of these markers before and after a mountain ultramarathon in young and inexperienced runners, unaccustomed to altitude. 20 runners (36.7 +- 6.3 years) were evaluated (6 females). They reported 4.0 +- 3.4 years competing in ultramarathon with a training load of 43.7 +- 16.8 km/week. The plasmatic values of troponin T (Trop-T HS) and N-terminal pro-brain natriuretic peptide (NT Pro-BNP) were determined before, immediately after the race and 24 hours later. The race was completed in 637.9 +- 197.5 minutes, and 55.1 +- 7.3 kilometers were covered. Both markers raised significantly after the competition. There was a statistically significant difference between the values of both determinations before the competition and at the end of the race (p < 0.0001) and between these and those after 24 hours (p < 0, 0001). At the end of the run, 95% of the sample presented NT Pro-BNP values above the diagnostic cut-off point of heart failure. All athletes presented values above the upper reference limit for Trop-T HS and 80% exceeded the diagnostic cut-off value for acute myocardial infarction. Troponin levels showed an inverse relation with weekly training (p = 0.04). There was a significant association between relative intensity of exercise and NT Pro-BNP levels after the competition (p = 0.001), where the group that completed the race with a heart rate higher than 80% of its maximum, significantly raised NT Pro-BNP. Conclusions: Trop-T HS and NT Pro-BNP significantly raised after the race. The extreme conditions and some characteristics of the athletes (poor habituation to altitude, short experience and relatively low volume of training) could justify these results. The clinical significance and mechanisms of these findings are still unknown, but the uniformity and brevity of the responses, as well the absence of clinical manifestations, suggest that they could represent an adaptive phenomenon. 107765 Modality: E-Poster Researcher - Non-case Report Category: ANTICOAGULATION Anticoagulation Control, Outcomes and Associated Factors in Patients Receiving Warfarin in Long-Term Care in Africa: A Systematic Review TAMRAT ASSEFA1, Gobezie Temesgen1, Dejuma Yadeta2, Legese Chelkaba1, Teferi Gedif1 (1) School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; (2) School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia Background: Oral anticoagulation therapy with warfarin requires frequent monitoring level of anticoagulation by the international normalized ratio (INR). Aims: This systematic review aimed to systematically summarize anticoagulation control, treatment outcomes, and associated factors in long-term patients receiving warfarin in Africa. Methods: The literature search was conducted in PubMed, Cochrane Library, African Journal of Online databases, Google Scholar, and Google. An advanced search strategy was computed to retrieve relevant studies related to anticoagulation control and outcomes. Duplication, title and abstract screening, and full-text assessment were conducted in Covidence software. Study quality was assessed using the Joanna Briggs Institute Critical appraisal quality assessment tool. The systematic review is registered in PROSPERO (CRD42021260772) and performed based on the PRISMA guideline. Results: Out of 298 identified articles, 18 articles were eligible for the final review and analysis. The mean of 39.4 +- 8.4% time in therapeutic range (TTR) (29.4% to 57.3%), 36.7 +- 11.5% TTR (range 25.2-49.7%) and 46% TTR (43.5-48.5%) was computed from studies that determined TTR by Rosendaal, direct and cross-section-of-the-files methods, respectively. The lowest percentage of TTR was 13.7%, while the highest was 57.3% was observed in this review. The highest percentage of patients (32.25%) who had TTR >= 65% was reported in Tunisia, but the lowest percentages were in Namibia (10%, TTR >= 65%) and Kenya (10.4%, TTR >= 70%). Generally, 10.4-32.3% of study participants achieved desired optimal anticoagulation level. Regarding secondary outcomes, 1.6-7.5% and 0.006-59% of patients experienced thromboembolic complications and bleeding events, respectively. The presence of chronic comorbidities, taking more than two drugs, and the presence of medications that potentially interact with warfarin were the frequently reported predictors of poor anticoagulation therapy. Conclusion: Oral anticoagulation control was suboptimal in patients taking warfarin as evidenced by low TTR in Africa. Therefore, there is an urgent need for further improving oral anticoagulation management service. 107767 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Thromboembolism and its Management in Hospitalized COVID-19 Patients using Modified Caprini Risk Score: A Single Center Experience in Ethiopia TAMRAT ASSEFA1, Ashenafi Teklu1, Alfoalem Araba1 (1) School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia Background: Reports indicated association of COVID-19 with coagulation dysfunction and venous thromboembolism (VTE) prevalence was in the range of 20-40%. All patients with COVID-19 who are hospitalized should receive pharmacologic prophylaxis unless they have contraindications. Aims: To assess VTE risk, incidence, and its management in patients with COVID-19 admitted to Tikur Anbessa Specialized Hospital (TASH). Methods: A retrospective study was conducted among 146 COVID-19 patients admitted to TASH. A pre-tested data abstraction format was used to collect patients' clinical information and VTE risk by using the modified Caprini Risk Score in COVID-19. We used Statistical Package for the Social Sciences (SPSS) version 26 for data analysis. Descriptive statistics were used to summarize the findings and binary logistic regression analysis to assess the association between the variables of interest. Results: Out of 146 patients, 57.53% were males and the mean age was 45.56 +- 18.17 years. All patients were at risk of developing VTE. The most often observed VTE risk factors were being COVID-19 symptomatic (88.40%), serious lung diseases (56.2%), and age >40 years (52.10%). The incidence of VTE was 23 (15.75%) and majorly (91.3%) occurred in highest VTE risk (>=5 scores) patients, >40 years patients, and in patients with severe COVID-19 symptoms (100%). However, parenteral thromboprophylaxis was prescribed only for 98 (67.12%) patients. Out of 23 patients who developed VTE, 15 didn't receive prophylaxis, and the remaining 8 received thromboprophylaxis. Unfractionated heparin (UFH) was the most widely used prophylaxis. For patients who developed VTE, the majority of them (86.96%) were given a therapeutic dose of UFH. Conclusion(s): All patients with COVID-19 were at risk of developing VTE. Only one-third received thromboprophylaxis. The incidence of VTE was high and majorly occurred in patients that didn't receive prophylaxis. 107796 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Cardioneuroablation Controlled by Extracardiac Vagal Stimulation for Treatment of Carotid Sinus Syndrome JUAN CARLOS ZERPA ACOSTA1, Jose Carlos Pachon Mateos2, Enrique Indalecio Pachon Mateos1, Carlos Thiene Cunha Pachon2, Juan Carlos Pachon Mateos1, Tasso Julio Lobo1, Tomar Guillermo Santillana Pena1, Felipe Augusto Ortencio1, Ricardo Cardneiro Amarante1, Maria Zelia Cunha Pachon2 (1) Hospital do Coracao - Sao Paulo; (2) SEMAP - Servico de Eletrofisiologia, Marca-passo, Desfibriladores, Ressincronizadores e Arritmias Prof. Dr. Jose Carlos Pachon M. Background: Carotid sinus syndrome (CSS) is a rare condition caused by sudden autonomic nervous system imbalance and Vagal overactivity that may lead to sinus arrest, AV block and syncope with severe symptoms commonly treated with pacemaker (PM). Since 2005 the Cardioneuroablation (CNA) procedure has been applied to aim vagal denervation through endocardial radiofrequency removing the cardio inhibition by ablation. Objective: To study the outcome of CNA controlled by extracardiac vagal stimulation (ECVS) in symptomatic functional CSS. Methods: Prospective, controlled study of 8 patients with symptomatic CSS, positive carotid sinus massage (CSM) and normal atropine response. Biatrial RF-ablation of the neuro endo-myocardial interface guided by filtered endocardial electrograms, fractionation, and 3D anatomical mapping, identifying type-1 AF-Nests (AFN) related to the 4 main ganglionated plexuses with FlexAbility Abbott irrigated catheter(30W/43degC/30s). ECVS(5s) at the right and left jugular foramen and CSM was performed before, during, and at the end of the ablation, to guide the level of denervation defining the higher CNA effect and end of the procedure, analyzing induced pauses and AVB. The endpoint was to eliminate complete pauses and AVB caused by ECVS and CSM. Results: Patients mean age was 58,6 (+-11,8). Pre-CNA ECVS and CSM response were sinus pauses (5,4 +- 1,3secs) and transient AVB 3/8. Post-CNA, ECVS, CSM and Atropine responses were completely abolished in 8/100%. There was observed immediate sustained HR increase (59.6 +- 12,7/81,7 +- 5,3bpm) as acute result. In a follow up of 28,1 (+-11,8) months there were no syncope recurrence. 1 patient had positive CSM at 6 months FU, without spontaneous syncope and had PM implanted. Conclusion: Bi atrial CNA vagal denervation based on AFN/GP ablation guided by abolishment of the vagal effect by ECVS and CSM response was effective for eliminating syncope recurrence in all the patients with CSS. 107798 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Influence of Severe Chronic Periodontitis on Left Ventricular Function, Inflammatory Markers and Microvascular Reactivity in Hypertensive and Normotensive Patients RITA DE CASSIA CASTELLI DA ROCHA1, Sergio Emanuel Kaiser1, Marcia Regina Simas Torres Klein1, Cyro Jose Morais Martins3, Ricardo Guimaraes Fisher2, Maria de Lourdes Guimaraes Rodrigues1, Debora Valenca1, Carolina Vicente Teofilo2, Carolina de Castelli da Rocha Carneiro3 (1) CLINEX - UERJ; (2) FACULDADE ; (3) HUPE Epidemiological studies suggest that chronic periodontitis (PD) associates with an increased risk of developing cardiovascular disease, whereas both share a link through inflammatory mediators. Arterial hypertension is a major risk factor for cardiovascular diseases, and it is believed that periodontal disease may favour its development. The relationship between PD and inflammation has been studied through biomarkers and assessment of endothelial function. Several conditions associated with subclinical inflammation seem to promote subtle changes in left ventricular systolic function, that can be detected by speckle tracking technology coupled with echocardiography. This study sought to explore, among hypertensive (HT) and normotensive (NT) individuals, the possible associations between severe chronic PD, inflammatory biomarkers, carotid intimal-medial thickness, and left ventricular systolic and diastolic function. The study consisted of a cross-sectional analysis with control for potential confounding factors, of 88 non-smoking, non-diabetic individuals of both sexes, among which, there were 50 AH under pharmacological treatment, and 38 NT. All underwent dental evaluation with a probe bag protocol aimed at identifying severe periodontitis, as well as laboratory tests (lipid profile, glucose, high-sensitivity C-reactive protei (HsCRP), interleukin-6 and tumor necrosis. They were broken down into 4 groups:AH/no PD; G3(N = 23):NT+PD; G4(N = 15):NT/no PD. Results: Mean age was 49.94 +- 7.32 (Range 35-60) years, 43% women; 39% non-white. Blood pressure (BP) mmHg: G1:136/82; G2:136/79; G3:125/79; G4:131/76 (p < 0.004 for systolic BP G3 vs G1). Mean BP was significantly higher in hypertensives (p < 0.01) regardless of severe PD. HsCRP (mg/dL) was significantly lower in G4 (p < 0.003); Intimal-medial thickness (IMT) was not significantly different among groups. Parameters of diastolic function did not differ significantly among groups regardless of the presence or absence of hypertension or PD. Global longitudinal strain (GLS) was also similar among groups; G1:-21.11 +- 2.24 G2:-21.33 +- 2.67 G3:-20.80 +- 3.17 G4:-21 +- 2.82 (p = 0.94). There were no significant differences in proportion of GLS >= -18 among the 4 groups. Since all HT patients were treated, no correlation systolic or diastolic BP and GLS was found. In conclusion, severe chronic PD was not independently associated with IMT, diastolic function nor with subclinical left ventricular dysfunction in the sample studied. 107816 Modality: E-Poster Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Methotrexate Associated with Lipid Core Nanoparticles Modulates Microrna-1 Expression that Prevents Left Ventricular Cardiomyopathy in Mice with Marfan Syndrome MARIA CAROLINA GUIDO1, Priscila Oliveira de Carvalho1, Natalia de Menezes Lopes1, Aline de Oliveira Silva1, Leonardo Jensen1, Roberto Kalil-Filho1, Lygia da Veiga Pereira2, Francisco Rafael Martins Laurindo1, Raul Cavalcante Maranhao1 (1) Instituto do Coracao - HCFMUSP; (2) Instituto de Biociencias - USP Introduction: Patients with Marfan syndrome (MFS), a disease caused by mutation of the fibrillin-1 gene, are vulnerable to left ventricular (LV) cardiomyopathy. MicroRNA-1 (miR-1) has involved in cardiomyopathy, but the role of miR-1 in MFS is unknown. Methotrexate (MTX), a chemotherapeutic agent, when associated with lipid nanoparticles (LDE) that mimic LDL composition, markedly increased cell uptake, which enhances the pharmacologic properties and diminishes the toxicity of the drug. LDEMTX showed powerful anti-inflammatory and anti-proliferative effects on rheumatoid arthritis and atherosclerosis rabbit models. In rats submitted to acute myocardial infarction, LDEMTX contributed to the reduction of LV remodeling. Objective: To investigate the effect of LDEMTX on miR-1 expression in the development of LV cardiomyopathy in MFS mice. Methods: MFS and wild-type (WT) mice were allocated to the following groups: WT and MFS, both untreated; MFS-MTX, MFS treated with commercial MTX; MFS-LDEMTX, MFS treated with LDE-MTX. The treatment occurred weekly at a dose of 1 mg/kg ip, between the 3rd and 6th month of life. After 12 weeks, the animals were submitted to echocardiography, morphometry and, miR-1 and proteins expressions of LV. Results: LDEMTX did not improve the LV diastolic dysfunction in MFS mice. LDEMTX reduced LV hypertrophy by decreasing the interventricular septum and posterior wall thickness and the myocytes diameter. Collagen volume fraction in subendocardial, interstitial and papillary muscle areas was also diminished. The protein expression of caspase 3 and hypoxia-inducible factor 2a were lower, whereas VEGF and angiopoietin 1/2 were higher in LDEMTX group. Compared to MFS and MFS-MTX groups, MFS-LDEMTX increased miR-1 expression. The expression of miR-1 had a negative correlation with pro-apoptotic (r2 = 0.48; p < 0.01), cellular hypoxia (r2 = 0.45; p < 0.01), fibrosis (r2 = 0.40; p < 0.01) and myocyte hypertrophy (r2 = 0.24; p < 0.05) markers; while had positive correlation with pro-angiogenic marker (r2 = 0.50; p < 0.01). Conclusion: Although LDEMTX had no effect on diastolic dysfunction, LDEMTX treatment improved cellular changes in LV cardiomyopathy in MFS mice. LDEMTX had beneficial effects on miR-1 modulation by increasing angiogenesis and decreasing apoptosis, cell hypoxia, fibrosis and hypertrophy of LV. This is the first study that shows therapeutic efficacy in the cardiomyopathy of MFS mice, under the modulation of miR-1. 107826 Modality: E-Poster Researcher - Non-case Report Category: DYSLIPIDEMIA Paraoxonase 1 (PON1) Activity in Patients with Familial Hypercholesterolemia and Subclinical Coronary Artery Disease FABIANA CORDEIRO JULIANI1, Fatima Rodrigues Freitas1, Viviane Zorzanelli Rocha1, Marcio Hiroshi Miname1, Ana Paula Chacra Marte1, Wilson Salgado1, Raul Dias Santos1, Raul Cavalcante Maranhao1 (1) Heart Institute of the Medical School, University of Sao Paulo - Brazil Introduction: Familial hypercholesterolemia (FH) is a monogenic disease characterized by elevated LDL-C from birth and increased risk of premature coronary artery disease (CAD). Accumulation of LDL-C in plasma may impair anti-atherosclerotic actions attributed to HDL. In addition to HDL particle size, metabolic aspects related to the antiatherosclerotic protection of HDL should be considered beyond simple determination of HDL-C, such as antioxidant action of HDL-associated paraoxonase 1 (PON1) that protects LDL and other lipoproteins from oxidative stress. Aim: To assess whether PON1 activity and HDL particle diameter are altered in individuals with FH with or without subclinical CAD. Methods: Twenty patients with genetic diagnosis of heterozygous FH and subclinical CAD documented by coronary CT angiography and 20 patients with heterozygous FH without subclinical CAD, matched by age, sex and BMI were enrolled. After 30-day interruption of lipid-lowering drugs, plasma lipids and apolipoproteins (apo) B and A-I were determined by commercial kits. LDL-C was calculated using the Friedewald formula. PON1 activity was determined by spectrophotometry. HDL diameter was determined by laser light scattering method. Results: LDL-C, non-HDL-C and apo B were equally high. There were no differences in triglycerides, HDL-C or apo A-I. PON1 activity and HDL diameter also did not differ between the two groups. Conclusion: Among patients with FH, the presence of subclinical CAD was not associated with significant differences in plasma lipids and apo's and in either HDL size or activity of PON1. In the quest for factors not related to high LDL-C that can facilitate or protect against the development of atherosclerosis in FH patients, other defects of HDL functions should be investigated. 107879 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Analysis of Regional Speckle Tracking and Tissue Doppler Strain in Identification of Coronary Arteries Responsible for Induction of Ischemia During 4D Stress-Echo with Adenosine Triphosphate in Patients with Stable Coronary Artery Disease NIKOLAI NELASOV1, Dmitry Safonov1, Nikolai Nelasov1, Alexander Zubov2, Maria Ovrulova1, Maxim Morgunov1, Roman Sidorov1, Olga Eroshenko1, Anna Nechaeva1, Georgiy Chudinov1, Anna Bazilevich1, Elizaveta Palenaja2 (1) Rostov State Medical University, Russian Federation; (2) Donetsk National Medical University, Ukraine Introduction: Analysis of left ventricular myocardial strain parameters during stress-Echo showed promising results in detection transient myocardial ischemia. Various echocardiographic modalities of strain analysis can be used: speckle tracking longitudinal (Ls), circumferential (Cs), radial (Rs), area (As) strain and tissue Doppler longitudinal strain (TDI Ls). However, it is still debatable which of these modalities better detects stress-induced ischemia in regions of vascularization of obstructed coronary arteries. Objectives. The objectives of this study were: 1) to explore which of the methods (Ls, Cs, Rs, As or TDI Ls) can more frequently reveal regional transitory deformation disorders and identify coronary arteries responsible for induction of ischemia in patients with stable obstructive coronary artery disease in dynamics of left ventricular 4D stress-Echo with adenosine triphosphate; 2) to compare the efficacy of conventional method of visual evaluation of local contractility and above mentioned strain modalities in detection of ischemia-associated obstructed coronary arteries. Methods: 32 patients (male 29, mean age 58,2 years (95% CI: 58,2-60,2 years) with stable angiographically documented coronary artery disease (single vessel obstructive disease was detected in 6, multi vessel - in 26 cases) underwent left ventricular 4D stress-Echo with adenosine triphosphate. Criterion of strain impairment during stress-test was an increase in values by 5% in at least 2 adjacent myocardial segments using Ls, Cs and TDI Ls methods, by 7% using As method, and decrease in strain value by 10% using Ra modality. Results: During stress-test Ls revealed appearance/increase of strain disorders in the regions of vascularization of obstructed coronary arteries in 71.9%, Cs - in 65.6%, Rs - in 59.4%, As - in 75.0% and TDI Ls - in 62.5% of patients, while visual assessment of LV myocardial contractility revealed impairment of contractility in the territories of vascularization of obstructed coronary arteries only in 31.2% of patients (differences with strain methods in all cases were statistically significant). Conclusion: All methods of regional strain analysis (Ls, Cs, Rs, As, TDI Ls) can identify coronary arteries responsible for induction of ischemia during 4D stress-Echo with adenosine triphosphate in patients with stable coronary artery disease more effectively then visual evaluation of myocardial contractility; the best results can be obtained by applying As. 107881 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Mortality and Predictors of Death in Women and Men with Congestive Heart Failure with Preserved, Mildly Reduced, and Reduced Ejection Fraction ANTONIO DE PADUA MANSUR1, Carlos Henrique Del Carlo1, Jose Antonio Ramos Neto1, Andre Barbosa de Abreu1, Airton Roberto Scipioni1, Antonio Carlos Pereira Barretto1 (1) Insituto do Coracao - HC FMUSP Background: Congestive heart failure (CHF) is one of the leading causes of death from cardiovascular disease and years lived with disability. Studies showed that women had better survival than men despite higher hospitalizations in women. However, little is known about differences in mortality and predictors of death in women and men with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods: From February 2017 to September 2020, we analyzed the mortality and the predictors of death in women and men with CHF (Framingham criteria). Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed with the Kaplan-Meier (K-M) method and the Cox proportional hazards methods to analyze death rates and search for predictors of death for women and men. Results: We studied 12,015 patients, mean of 63.8 +- 14.3 years, 6637 (55%) males. Females were older (64.9 +- 14.8 vs. 62.8 +- 13.8 years; p < 0.0001), had a higher baseline mean left ventricular ejection fraction (LVEF) (49.8 +- 18.9% vs. 42.6 +- 15.4%; p < 0.001), and a lower left ventricular diastolic diameter (LVDD) (54.1 +- 9.0 vs. 60.1 +- 9.6 mm; p < 0.001). Over a 3-years follow-up period, 1543 (23.2%) men and 1051 (19.5%) women of the cohort died (K-M: log-rank p < 0.0001). Cumulative incidence of death was higher in men (K-M: log-rank p = 0.0002) with HFrEF but similar for HFmrEF and HFpEF . Cox regression for death adjusted for age, ischemic, idiopathic, hypertension, Chagas, valve, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation, and LVEF showed that CKD, previous stroke, and diabetes were the main predictors of death for all phenotypes of LVEF in women and men. Conclusion: Women had a better prognosis than men in HFrEF but similar mortality for HFmrEF and HFpEF. Control of diabetes and preventing stroke and CKD could significantly reduce the death rate in women and men with all CHF phenotypes. 107882 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Mortality and Predictors of Death in Women and Men with Congestive Heart Failure of Different Types of Cardiomyopathies ANTONIO DE PADUA MANSUR1, Carlos Henrique Del Carlo1, Jose Antonio Ramos Neto1, Andre Barbosa de Abreu1, Airton Roberto Scipioni1, Antonio Carlos Pereira Barretto1 (1) Insituto do Coracao - HC FMUSP Background: Congestive heart failure (CHF) is one of the leading causes of death from cardiovascular disease and years lived with disability. Studies showed that women had better survival than men despite higher hospitalizations in women. However, there is evidence of a gender-associated risk of dying of heart failure of different types of cardiomyopathies (CMP). Purpose: To analyze the mortality of CHF due to different types of CMP in women and men. Methods: From February 2017 to September 2020, we analyzed the mortality and the predictors of death in women and men with CHF (Framingham criteria) in five types of CMP (ischemic, idiopathic, hypertensive, Chagas, and valve disease). Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses used the Kaplan-Meier (K-M) method and the Cox proportional hazards methods to analyze death rates and search for predictors of death for women and men for each CMP. Results: We studied 12,015 patients, mean of 63.8 +- 14.3 years, 6637 (55%) males. For all patients, death occurred in 27.5%, 15.3%, 17.5%, 40.1%, and 24.4%, respectively, for ischemic, idiopathic, hypertensive, Chagas, and valve CMPs (p < 0.0001). HFrEF was more prevalent in idiopathic (51.2%) and Chagas (49.9%), and for HFpEF valve disease (80.4%), hypertensive (51.9%), and ischemic (44.4%). Compared to men, women were older, had a higher baseline mean left ventricular ejection fraction (LVEF), and a lower left ventricular diastolic diameter (LVDD) for all five types of CMP (p < 0,001). Over a 3-years follow-up period, the cumulative incidence of death was higher in men with ischemic CMP (38% vs. 31%; p = 0.037) and Chagas CMP (48% vs. 38%; p < 0,001) but similar for idiopathic, hypertensive, and valve disease CMP . Cox regression analysis for death, for each CMP, adjusted for confounders such as age, sex, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation (AF), any cardiac surgery, cardiac pacemakers, and LVEF showed that men were an independent predictor of death only for Chagas CMP (HR = 1,28; 95%CL: 1.08-1.43; p = 0.009). Conclusion: Men were at a higher risk of death in ischemic and Chagas CMP but not for idiopathic, hypertensive, and valve CMP. The other main predictors of death were similar for all types of CMP, namely CKD, stroke, diabetes, and AF. 110849 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION The Fuzzy Logic Approach in the Prevention of Sudden Cardiac Arrest MICHAL LEWANDOWSKI1 (1) National Institute of Cardiology, Warsaw, Poland Introduction: Sudden cardiac death (SCD) constitutes a major clinical and public health problem, whose death burden is comparable to the current worldwide pandemic. The presented abstract and project encompasses the following topics: available rescue systems, wearable electrocardiograms (ECG), detection and transmission technology, and a newly developed fuzzy logic algorithm (FA) for heart rhythm classification which is state-of-the art in the field of SCD prevention. Project "PROTECTOR", the Polish Rapid Transtelephonic ECG System to Obtain Resuscitation for development of a rapid rescue system is presented. Methods: From a database containing RR interval series of the recorded arrhythmia events and controls, stored in the defibrillator memory and archived on PC during systematic control visits, RR data was chosen consecutively on the basis of full data availability, i.e., RR interval series with simultaneous intracardiac electrogram (IEGM) prints. Then, the heart rhythm classification of the recorded event was assigned into one of the six diagnostic categories of the developed algorithm. The total number of RR recordings evaluated for statistical analysis came to 298 (obtained from 183 pts). Sensitivity and specificity of the proposed algorithm were calculated on the basis of the widely accepted criteria. If a lethal arrhythmia is detected on the basis of FA, the system produces an alarm signal audible for bystanders and transmits the alarm message along with location to the emergency medical center. Phone guided resuscitation can be started immediately because an automated external defibrillator (AED) localization map is available. An automatic, very fast diagnosis is a unique feature of the PROTECTOR prototype. Results: The sensitivity and specificity of the tested algorithm were 100% and 97.8%, respectively. Internet data transfer opens potential application of the presented heart rhythm classification in telemedicine. The presented methodology is completely new ECG-based technique in the diagnosis and treatment of cardiac patients. Conclusions: The rapid detection of SCA is based on a processor characterized by 100% sensitivity (as measured in the pilot studies). An integrated circuit which implements FA has already been designed and a diagnosis is made within few seconds, which is extremely important in ischemic brain damage prophylaxis. This algorithm could be implemented in many mobile devices: smartphones, tablets etc. 107971 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Reference Ranges of Filling Time and Systolic-to-Diastolic Time Index of the Left Ventricle, Right Ventricle and Interventricular Septum using Both Spectral and Tissue Doppler of Fetal Heart between 20 and 36+6 Weeks of Gestation NATHALIE JEANNE MAGIOLI BRAVO-VALENZUELA1, Alberto Borges Peixoto3, Mattar, Rosiane2, Antonio Fernandes Moron2, David Baptista da Silva Pares2, Gabriele Tonni4, Edward Araujo Junior2 (1) FEDERAL UNIVERSITY OF RIO DE JANEIRO-RJ, Brazil; (2) FEDERAL UNIVERSITY OF SAO PAULO-SP, Brazil; (3) Federal University of Triangulo Mineiro-MG, Brazil; (4) Prenatal Diagnostic Service, Department of Obstetrics and Gynecology, Istituto di Ricerca a Carattere Clinico Scientifico (IRCCS), AUSL Reggio Emilia, Italy ABSTRACT Purpose: To establish reference values for the systolic-to-diastolic duration ratio (SDR) of the left ventricle (LV) using spectral Doppler, as well as for the SDR' of the interventricular septum (SEP), LV, and right ventricles (RV) using tissue Doppler of the fetal heart. Methods: This prospective and cross-sectional study evaluated 374 low-risk singleton pregnancies from 20 to 36+6 weeks of gestation. The ventricular filling time (FT) was obtained from LV inflow using spectral Doppler. Tissue Doppler was used to assess the FT of each ventricle by placing the cursor at the atrioventricular junction marked by the mitral and tricuspid valves, respectively. SDR was calculated as the sum of the isovolumic contraction time (ICT) and the ejection time (ET) divided by the sum of the isovolumic relaxation time (IRT) and the ventricular FT. We used regression analysis to obtain the best-fit model polynomial equation for the parameters. The concordance correlation coefficient (CCC) was used to assess inter-observer reproducibility. Results: SDR and SDR' LV showed a progressive decrease with gestational age (GA); the SDR' RV and SDR' SEP did not show a significant decrease with advancing GA. The SDR LV (r = 0.29, p < 0.0001), SDR' RV (r = 0.21, p < 0.0001), SDR' LV (r = 0.20, p = 0.0001), and SDR' SEP (r = 0.25, p < 0.0001) showed a significant weak positive correlation with fetal heart rate. The inter-observer SDR' SEP measurements demonstrated poor reproducibility (CCC: 0.50), whereas intra-observer SRD LV measurements demonstrated moderate reproducibility (CCC: 0.78). Conclusions: Reference values for SDR SEP, LV, and RV using spectral and tissue Doppler of fetal heart were established between 20 and 36+6 weeks of gestation. 108035 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID-19 Pandemic on Hospitalizations, Mortality Rate and Length of Stay in Patients with Pulmonary Embolism (PE) in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Objectives: The novel coronavirus (SARS-CoV-2) may predispose patients to arterial or venous thrombosis due to excessive inflammation, platelet activation, endothelial dysfunction, and blood stasis. Pulmonary embolism as one of the most serious manifestations of this systemic framework worries those who are dealing with COVID-19 daily. The need for isolation and the home office can favor the development of risk factors for PE such as a sedentary lifestyle, immobility, obesity and smoking. The present study aimed to assess the influence of COVID-19 on hospitalizations, mortality rate and length of stay for pulmonary embolism in Brazil. Method: We used the database from the Department of Informatics of the Brazilian Health System (DATASUS), through the website We evaluated the number of hospitalizations, deaths and length of stay of patients for PE in Brazil and their relationship with the beginning of the COVID-19 pandemic in Brazil (March 2020) based on data from January 2018 to December 2021. Results: From January 2018 to December 2021, 38902 patients were hospitalized for PE in Brazil, 23706 (60.9%) were female and 15196 (39.1%) were male. There was a slight increase in the average number of hospitalizations, but there was no statistical difference in the average total number of hospitalizations comparing 2018-19 with 2020-21: 9655 +- 624 and 9797 +- 201 (p = 0.804). The number of deaths and mortality rate also did not show important differences for the same period, with 1684 +- 66 deaths and a mortality rate of 17.5 +- 0.43 for 2018-19 and 1805 +- 142 and a mortality rate of 18.4 +- 1.1 for 2020-21 (p = 0.428 and p = 0.415 respectively). The mean hospital stay was similar, with 9.1 +- 0.3 days in 2018-19 and 8.5 +- 0 days in 2020-21 (p = 0.205). Regarding the age group, the number of hospitalizations is higher between 60-69 years old with 7495 cases and an annual average of 1874 +- 59 and the group over 80 years old with the highest mortality rate 34.7 +- 1.5. Conclusion: In the context of the COVID-19 pandemic, the number of hospitalizations due to PE remained stable in the period studied from 2018 to 2021, with a predominance of female patients (60.9%). The number of deaths and mortality rates also remained stable, as well as the average length of hospital stay. Advanced age was an important factor for both hospitalization and mortality. 108036 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Influence of the COVID-19 Pandemic and Vaccination on Deaths from Stroke in the Elderly Population in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Objective: Cardiovascular diseases are increasingly becoming a health problem in Brazil and worldwide. They are related to important acute complications such as stroke, which have high morbidity and mortality, especially when identified late. Taking into account the difficulty of the population's access to health services in brazilian pandemic scenario, the present study aimed to assess the impact of COVID-19 pandemic and vaccination on stroke deaths in the elderly population in Brazil. Method: Using data from the Civil Registry Information Center in Brazil, through the website we evaluated the number of deaths from stroke in Brazil in the elderly (age above 60 years) and its relationship to the COVID-19 pandemic from January 2019 to December 2021. Results: From January 2019 to December 2021, 239771 patients above 60 years old died of stroke in Brazil, 120107 (50.1%) were male and 119664 (49.9%) female. There was a slight decrease in stroke deaths in the comparison between 2019 and 2020, from 79806 to 79435 with a further increase in 2020 to 80530. The age group with the highest number of deaths was 80-89 with an average of 25807 +- 519, followed by 70-79 with an average of 25180 +- 1012. When we compare the monthly average of deaths and the beginning of the pandemic in Brazil (March 2020), the average was: before 656 +- 44 and after 673 +- 23 (p = 0.27). We also performed an analysis with the start of vaccination in Brazil in January 2021 and found a mean number of monthly deaths of 673 +- 23 before and 671 +- 46 after (p = 0.89). Conclusion: In the context of the Brazilian COVID-19 pandemic scenario, the number of deaths from stroke in the elderly population fell slightly from 2019 to 2020, with a new increase in 2021. The number of deaths remained similar for the years studied, with the age group of 80-89 years old as the highest number of cases followed by the 70-79 group. Neither the COVID-19 pandemic nor vaccination changed the monthly average deaths from stroke in the Brazilian elderly population. 108037 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID-19 Pandemic on Deaths from Stroke in Young People in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Objectives: The cardiovascular diseases are an important healthcare problem in Brazil and worldwide. They are related to acute complications such as stroke, which have high morbidity and mortality, especially when identified late. The difficulty of the population's access to health services in brazilian pandemic scenario associated to isolation and home office can favor the development of traditional risk factors for stroke, most often neglected by young people, as sedentary lifestyle, obesity, smoking and poor nutrition. The present study aimed to assess the impact of COVID-19 on stroke deaths in young people in Brazil. Method: We used data from the "Portal da Transparencia", a platform managed by the National Association of Registrars of Natural Persons (Arpen-Brazil), through the website We evaluated the number of deaths from stroke in Brazil in young people (aged 20 to 59 years) and its relationship with the beginning of the COVID-19 pandemic in Brazil (March 2020) analyzing data from January 2019 to December 2021. Results: From January 2019 to December 2021, 57,965 patients between 20 and 59 years old died from stroke, 33,764 (58.2%) were male. There was an increase in the number of total deaths over the years studied from 17506 to 19042 and 21417. The average monthly deaths in the period before the pandemic in Brazil was 1451 +- 80, in contrast to 1711 +- 117 after the beginning of the pandemic (p < 0.001). The age group with the highest number of deaths was 50-59 with a mean of 10246 +- 788, followed by 40-49 with a mean of 5215 +- 488. Conclusion: According to official data on deaths from strokeI in young adults between 20 and 59 years old, there was a progressive increase from 2019 to 2021, with a predominance of male patients. The COVID-19 pandemic contributed to this increase significantly. Age remains an important risk factor and older age groups continue to be the most affected. 108038 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID-19 Pandemic on Deaths from Acute Myocardial Infarction (AMI) in Young People in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Objectives: Cardiovascular diseases are one of the main causes of death in Brazil and worldwide, and AMI is its main exponent. During the pandemic of the new coronavirus, health systems had to adapt to adequate care of these patients. The need for isolation and home office can favor the development of traditional risk factors for AMI, most often neglected by young people, such as a sedentary lifestyle, obesity, smoking, excessive consumption of alcohol, stress and poor nutrition. In addition, and taking into account the difficulty of the population's access to health services in the Brazilian pandemic scenario, the present study aimed to evaluate the impact of COVID-19 on deaths from AMI in young people in Brazil. Method: We used data from the "Portal da Transparencia", a platform managed by the National Association of Registrars of Natural Persons (Arpen-Brazil), through the website We evaluated the number of deaths from AMI in Brazil in young people (aged 20 to 59 years) and its relationship with the beginning of the COVID-19 pandemic in Brazil (March 2020) with data from January 2019 to December 2021. Results: From January 2019 to December 2021, 64,512 patients between 20 and 59 years old died from AMI, 44,940 (69.7%) were male. There was an increase in the number of total deaths over the years studied from 20075 to 20706 and 23731. The average monthly deaths in the period before the pandemic in Brazil was 1680 +- 123, in contrast to 1862 +- 181 after the beginning of the pandemic (p = 0.001). The age group with the highest number of deaths was 50-59 with a mean of 13568 +- 766, followed by 40-49 with a mean of 16710 +- 533. Conclusion: According to official data on deaths from AMI in young adults between 20 and 59 years old, there was a progressive increase from 2019 to 2021, with a predominance of male patients. The COVID-19 pandemic contributed to this increase significantly. Age remains an important risk factor and older age groups continue to be the most affected. 108078 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Outcomes of Pregnant Women with Non-Compaction Cardiomyopathy: Cases Series from WALKIRIA SAMUEL AVILA1, Daniel VInicius Rodrigues Pinto1, Vera Maria Cury Salemi1, Walkiria Samuel Avila1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (2) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (3) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (4) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Background: Non-compaction cardiomyopathy (NCC) is a genetic congenital disease, with adverse clinical manifestations. The circulatory overload and hypercoagulability status of pregnancy, both can lead to serious complications. Purpose: To study the maternal and fetal outcomes of pregnant women with NCC. Methods: Out of 495 pregnant women with heart disease studied, four of them had a diagnosis of NCC confirmed by echocardiography and/or cardiac magnetic resonance exams. Before pregnancy, the symptoms were angina pectoris, syncope, and three cases with symptomatic arrhythmias, two of them underwent radiofrequency ablation. In the multidisciplinary follow-up, the therapy management was adjusted for pregnancy. Results: The Table below presents the characteristics of patients and the maternal-fetal evolution. There were no deaths, but three patients required hospitalization for treatment of heart failure and cardiac arrhythmias, right away emergency cesarean section resulting premature babies. In the follow-up-12months, no changes were observed in the clinical or myocardium remodeling of NCC patients. The investigation of newborns did not identify any case of NCC. Conclusions: The heterogeneity of NCC expression and the proportion of maternal and fetal complications, observed in this series, discourage pregnancy in patients with NCC. However, if pregnancy occurs, it should be followed into a tertiary hospital with a multidisciplinary team on standby. 108095 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Global Prevalence of Depression and Anxiety in Adolescents and Adults with Congenital Heart Disease: A Systematic Review and Meta-Analysis PHILIP MOONS1, Liesbet Van Bulck1, Koen Luyckx1 (1) KU Leuven - University of Leuven, Belgium Background: Living with congenital heart disease (CHD) and the required invasive treatments are believed to have an impact on the psychological health of afflicted individuals. Therefore, mental health in persons with CHD is an area of concern. The epidemiology of depression and anxiety in CHD, however, is not fully understood and literature seems to report contradictory findings. Objective: We aimed (i) to estimate the proportion of depression and anxiety in adolescents and adults with CHD around the globe; and (ii) to explore differences in depression and anxiety rates between people with CHD and the general population. Methods: We conducted a systematic literature review and meta-analysis, registered in PROSPERO (CRD42021228395). Searches were performed in PubMed, Embase, Cinahl and Web of Science from their inception to March 6, 2021. We identified 91 studies, which enrolled 180,176 patients in total. A random effects meta-analysis of single proportions was conducted according to the DerSimonian-Laird method. Hedges' gu (g) was calculated to compare the level of depression and anxiety with the general population. Results: The pooled estimated proportion showed that 21.1% of the people with CHD had >=mild depressive symptoms and 10.3% had >=moderate depressive symptoms. When looking at the clinical diagnosis of depression, 10.3% had actual depression, and 16.1% had a lifetime episode of depression. For anxiety, 42.7% had >=mild anxiety symptoms and 21.9% had >=moderate anxiety symptoms. A clinical anxiety disorder was found in 12.7%, and 23.3% had a lifetime episode of anxiety disorder. The mean scores on questionnaires assessing symptoms of depression (g = 0.215; 95%CI = 0.062-0.368) or anxiety (g = 0.292; 95%CI = 0.165-0.419) were significantly higher in CHD than in the general population. However, this higher symptom score was not reflected in a significantly higher proportion of CHD patients having >=mild depressive symptoms (p = 0.654), >=moderate depressive symptoms (p = 0.869), >=mild anxiety symptoms (p = 0.055) or >=moderate anxiety symptoms (p = 0.287), when using the predefined cut-off scores. Conclusions: This meta-analysis showed that there is a high proportion of depression and anxiety in persons with CHD. Although patients with CHD had higher scores of depressive and anxiety symptoms than people from the general population, the prevalence of depressive or anxiety symptomatology was not higher in CHD. 111457 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE High Spirituality Score Protects Against Burnout and its Consequences Among Brazilian Cardiologists MAURO RICARDO NUNES PONTES1, Mario Borba2, Lucelia B. N. C. Magalhaes3, Alvaro Avezum4, Emilio Moriguchi5, Roberto Esporcate6, Sergio Livio Menezes Couceiro7, Hermilo Borba Griz8, Fernando A. Lucchese9 (1) Nucleo de Pesquisa Clinica do RS; (2) Cardioclinica do Vale, Lajeado; (3) UniFTC-Faculdade de Ciencia e Tecnologia; (4) Hospital Alemao Osvaldo Cruz; (5) Hospital de Clinicas de Porto Alegre; (6) Faculdade de Ciencias Medicas, UERJ; (7) Universidade Federal Fluminense; (8) Hospital Santa Joana, Recife; (9) Hospital Sao Francisco, Santa Casa de Porto Alegre Purpose: Burnout among physicians is frequent and has several consequences for physician and patient. We hypothesized that high spirituality protect against burnout. Methods: A survey with cardiologists, Aug 2018, asked about Burnout, demographics, spirituality, religiosity, job characteristics. We measured Burnout by 3 validated questions (three MBI -Maslach Burnout ). Subjects were Burnout + (B+) if they were in the top 3 scores (">once a week") on emotional exhaustion and/or depersonalization. Demographics, Spirituality score, DUREL religion index, job aspects, were correlated with B+ or B-. We evaluated consequences of burnout (suicidal ideation, stress, anxiety, depression measured by the DASS-21 form). Multivariate models evaluated the adjusted impact of spirituality over burnout and its consequences. Statistical analysis with SPSS version 23. Results: 1000 survey forms, 40.5% response rate; 39 excluded (4 incomplete, 35 graduated PS2y); final sample, 375 cardiologists; age 48.8 +- 12.6y, male 57.3%. Burnout rate was 34.6%. Variables associated with Burnout in bivariate analysis: civil state (divorced/single 28.9% B+, married 6.8%, P = 0.020), years from graduation (B+, 20.3 +- 13.1y; B-, 25.3 +- 12.5y; P < 0.001), age (B+, 45.4 +- 13.1y; B-, 50.0 +- 12.4y; P = 0.001), duty hours/week (Q1 to Q4; 24.0%, 27.8%, 46.5%, and 60.9%; P < 0.001), and night shifts/week (0 to 3; 30.7%, 38.2%, 41.7%, and 71.4%; P = 0.001). Gender (P = 0.295), Spirituality score (P = 0.099), DUREL (P > 0.05 for all 3 domains), postgrad (P = 0.701) and subspecialty (P = 0.668) not associated with B+. Consequences of Burnout: suicidal ideation (B+, Yes 10.9%; 1.3%; P < 0.001), DASS Global score (B+, 18.1 +- 11.7; B-, 8.1 +- 6.8, P < 0.001), and DASS subscales of Anxiety, Stress, and Depression (P < 0.001 for all) were all associated with B+. In a multivariate regression model (Table 1), Number of Duty Hours per Week was associated with Burnout (OR = 1.79, 95% CI 1.34-2.41, P < 0.001), while Spirituality Score (but not Religiosity by DUREL index) protected against Burnout (OR = 0.87, 95% CI 0.77-0.98, P = 0.043). Conclusions: High number of duty hours per week increases Burnout among Brazillian cardiologists, while high Spirituality protects them against Burnout. 108248 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Impact of Existing Cardiovascular Risk Factors on the Improvement of Exercise Tolerance in Patients with Coronary Artery Disease After PCI and Cabg Undergoing Early Post-Hospital Cardiac Rehabilitation EDYTA SMOLIS-BAK1, Ilona Kowalik1, Jurand Sloniewicz1, Ewa Rydzewska1, Iwona Korzeniowska-Kubacka1, Jadwiga Wolszakiewicz1, Rafal Dabrowski1, Edyta Smolis-Bak1 (1) National Institute of Cardiology Background: Regular physical activity is crucial for treatment and prevention of cardiovascular diseases. Adaptive changes in response to regular physical exertion show individual variability, which depends on a number of internal and external factors. The aim of the study was to assess the effectiveness of early post-hospital rehabilitation and to analyze the factors which may influence the exercise tolerance in patients with coronary artery disease (CAD) treated with PCI and CABG. Material and methods: The study included 334 patients (pts), men 75.1%, with CAD, treated with PCI (87.4%) or CABG (12.6%). Mean age of the study group was 61.1 +- 10.9 years, mean BMI: 27.6 +- 4.1 kg/m2, mean LVEF: 56.1 +- 7.2%. The main risk factors for CAD were: dyslipidemias: 76%, hypertension: 64.7%, smoking: 28.7%, diabetes: 22.5%. The rehabilitation procedures lasted for 6-8 weeks. Pts participated in endurance training and general conditioning exercises with elements of resistance trainings. Before and after rehabilitation, all patients underwent a symptom-limited exercise test (ETT). In order to identify factors influencing the increase in tolerance of training loads, patients were divided into 2 groups: group 1 (198 pts, 59.3%) - pts with the training load which increased >=50%, group 2 (136 pts, 40.7%) - pts with training loads which increased less, by <50%. Results: After rehabilitation, a significant improvement in the ETT parameters was observed: 5.7 +- 1.3 vs. 6.8 +- 1.7 METs, p < 0.001; the resulting load predicted for age: 81.5 +- 22.5 vs. 93.7 +- 22.89%, p < 0.001; tests duration: 352 +- 106 vs. 436 +- 136 sec., p < 0.001 and in the training loads obtained: 46.7 +- 10.9 vs. 71.4 +- 22.4 Watts, p < 0.001. On the other hand, after rehabilitation, a significant increase in the number of pts with supraventricular (24.2% vs 34.7%, p < 0.001) and ventricular (34.2% vs 40.5%, p < 0.02) arrhythmias was observed. There was no correlation between the increase in training load tolerance (Watt) and the METs increase in the final ETT. The increase in the tolerance of training loads of >=50% during rehabilitation was significantly influenced by: younger age, p < 0.001, gender (men), p < 0.001, EF (>50%), p < 0.003, absence of diabetes, p < 0.003, lower initial values of training loads, p < 0.003. The increase in workload (MET > 50%) in the final ETT was significantly influenced by age (younger patients), BMI (thinner subjects) and lower workload (MET) in the baseline test. Other factors: smoking, hypertension. 108254 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Sexual Dysfunction in Patients After Implantation of Left Ventricular Assist Device, LVAD EDYTA SMOLIS-BAK1, Edyta Smolis-Bak1, Zbigniew , Monika Szymanska2, Ilona Kowalik1, Ryszard Piotrowicz1, Eliza Noszczak1, Rafal Dabrowski1 (1) National Institute of Cardiology, Warsaw, Poland; (2) Postgraduate Medical Education Center, Warsaw, Poland Background: Data show that cardiological patients (pts), after achieving an improvement in the functioning of the cardiovascular system, begin to expect improvement also in the field of sexual health, which is important in partner relationships, mental health and quality of life. The aim of the study was to analyze the occurrence of sexual disorders and to assess the impact of sexual rehabilitation and physiotherapeutic education on sexuality in pts after left ventricular assist device (LVAD) implantation. Material and methods: The study included 50 men after LVAD implantation, mean age 51.6 +- 12.8 years. 18 pts did not complete the study (heart transplant -5 pts, resignation -10 pts, death -3 pts). The pts were assessed by a sexologist in terms of the quality of sexual life and erectile dysfunction. All pts received therapeutic interventions: sexological counseling, education (positions during intercourse, safety recommendations) and physical activity. Additionally, pharmacological treatment of erectile dysfunction was started in 15 pts. Upon entry into the study, the quality of sexual life, sexual needs (Mell-Krat scale) and sexual function (International Index of Erectile Function, IIEF-5) were assessed retrospectively (before the onset of the disease) and actually. Additionally, exercise tolerance was assessed using the 6-minute walk test (6-MWT). The tests were repeated after 6 months. Results: After the implementation of sexual and physical activity education, significant improvement in exercise tolerance assessed by 6-MWT [m] was observed: 350 (310-445) vs. 450 (400-500), p < 0.001. The quality of sex life in the whole group significantly worsened after LVAD implantation compared to the period before the onset of the disease (40 [40-41] vs 33.5 [12-40] vs 34 [26-40]). Mild erectile dysfunction was observed in all the pts, both before onset of the disease, after LVAD implantation and after 6 months. The number of pts with sexual dysfunction increased significantly after LVAD implantation (9.4% vs. 53.1%) and remained at a similar level for 6 months. There was a significant reduction in the frequency of sexual intercourse after LVAD implantation and a significant increase in it after pharmacological treatment, but its level did not reach the level before the disease (3 [2-4] vs 1.5 [0-2.5] vs 2 [1.0-2.5]). The improvement in the quality of sexual life and the reduction of erectile dysfunction were significantly dependent on age and LVEF - bett. 108346 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Cardiovascular Mortality in Brazil During the COVID-19 Pandemic: Comparison between Underlying and Multiple Causes of Death Analysis LUISA CAMPOS CALDEIRA BRANT1, Pedro Cisalpino Pinheiro1, Luiz Guilherme Passaglia1, Eduardo David Gomes de Sousa2, Carla Valenca Daher2, Roberta Maria Leite Costa2, Antonio Luiz Pinho Ribeiro1, Bruno Ramos Nascimento1 (1) Faculdade de Medicina e Hospital das Clinicas, Universidade Federal de Minas Gerais, UFMG, Brazil; (2) Department of Specialized and Thematic Healthcare, Ministry of Health, Brasilia, Brazil Introduction: COVID-19 has impacted cardiovascular (CV) mortality worldwide, possibly due to avoidance of healthcare, health system collapse, and the direct CV effects. Data from Brazil are scarce and restricted to some locations or early phases of the pandemic. Objective: To evaluate the impact of COVID-19 pandemic on mortality for CV diseases (CVD), stratified by age, sex and region of Brazil, comparing underlying (UC) and multiple causes (MC) of death. Methods: Ecological, time series study analysing the age-standardized death rates for CVD, from epidemiological week (EW) 10/2020 to EW 11/2021, using data from the Mortality Information System (SIM-SUS). CVD was defined as in Chapter IX, ICD-10, and considered if reported as UC or MC of death (UC + other causes reported in any line of death certificate), in separate analyses. Observed was compared to expected data (mean for the same EW of 2017-2019). Risk ratios (RiR) were analysed and 95% confidence intervals were calculated. Results: Age-standardized mortality rate for CVD as UC of death in the pandemic was 136.8 (95%CI 136.3-137.3)/100,000 inhabitants, 7% (RiR = 0.93; 95%CI 0.93-0.93) lower than expected (147.1; 95%CI 146.6-147.6)/100,000. There was an increase in out-of-hospital mortality (6%) (RiR = 1.06; 95%CI 1.05-1.07) and in deaths with ill-defined CVD causes (49%) (RiR = 1.49; 95%CI 1.47-1.50), particularly in the out-of-hospital setting (58%). The increase in out-of-hospital deaths was more pronounced in the North (RiR = 1.27; 95%CI 1.25-1.28) and Northeast (RiR 1.18; 95% CI 1.17-1.18) regions, both with less structured health systems. Conversely, in MC of death analysis, there was a 4% increase in CV mortality (observed: 225.1 (CI95% 224.5-225.8), expected: 217.2 (95%CI 216.5-217.8)/100,000, RiR: 1.04 (95%CI 1.03-1.04), noticeably in the out-of-hospital setting (11%). In MC of death analysis, the steeper increasing trends also ocurred in the North region (RiR = 1.13; 95%CI 1.12-1.15), and in individuals >60 years (RiR = 1.05; 95%CI 1.05-1.06), and among men (RiR: 1.06; 95%CI 1.05-1.06) vs. women (RiR: 1.02; 95% CI 1.01-1.02). Conclusions: During the pandemic, mortality rates for CVD as UC of death reduced in Brazil, contrasting with an increase when MC were considered. Higher out-of-hospital mortality - resulting from social distancing and overwhelmed health systems - exaberbation of existing CVD by COVID-19, and competing causes of death may have accounted for this pattern. 108258 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Does Early Hospital Rehabilitation Contribute to the Reduction of Falls in Patients After Cardiac Surgery? EDYTA SMOLIS-BAK1, Kamil Szczesniak1, Ilona Kowalik1, Grzegorz Skorupski1, Lukasz Lasecki1, Jerzy Osak1, Magdalena Furmanek1, Hanna Szwed1, Rafal Dabrowski1 (1) National Institute of Cardiology, Warsaw, Poland Balance and coordination disorders are factors provoking falls in the elderly. Their fast and precise identification is therefore of vital importance. The aim of this work was to assess the risk of falls and the influence of early hospital rehabilitation on the balance and coordination parameters in patients after cardiac surgery. Material and methodology: The study was conducted on 207 patients: 44 women and 163 men aged 18-87 (mean 60.2 +- 14.0), who participated in comprehensive cardiac rehabilitation following cardiac surgery. The risk of falls and patients' functional status were tested twice with the use of the FallSkip device: after the initial mobilization and before the discharge from the ward. Results: After rehabilitation, improvement was noted in the whole group in all analysed functional parameters and in the reduction of the risk of falls (p < 0.0001). A significantly higher risk of falls was observed in women in comparison with men (p < 0.001), and in individuals aged >70 in comparison with patients aged <70 (p < 0.001). There were no differences observed in the risk of falls of patients in the groups with the BMI <30 and >30, both before and after rehabilitation. After rehabilitation the risk of falls decreased significantly in men (p < 0.001) and in individuals aged <70, (p < 0.001), as well as in patients with the BMI <30, p < 0.001, and >30, p < 0.012. There was a tendency for better results in men in all tested parameters. Conclusions: The proposed comprehensive rehabilitation model after cardiac surgery significantly improved the effectiveness of gait, time of reaction in response to audio stimuli, increased muscular strength of lower limbs and significantly reduced the risk of falls. The FallSkip equipment is useful in the assessment of the risk of fall and of the level of functional parameters in patients after cardiac surgery. 108351 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Indirect Effect of COVID-19 Pandemic in Hospitalizations for Cardiovascular Diseases in Brazil: Reduced Numbers with Higher In-Hospital Deaths LUISA CAMPOS CALDEIRA BRANT1, Luiz Guilherme Passaglia1, Pedro Cisalpino Pinheiro1, Eduardo David Gomes de Sousa2, Carla Valenca Daher2, Roberta Maria Leite Costa2, Antonio Luiz Pinho Ribeiro1, Bruno Ramos Nascimento1 (1) Faculdade de Medicina e Hospital das Clinicas, Universidade Federal de Minas Gerais, UFMG, Brazil; (2) Department of Specialized and Thematic Healthcare, Ministry of Health, Brasilia, Brazil Introduction: The COVID-19 pandemic impacted hospitalizations for other causes due to change in populations' behaviour, as a result of fear or adherence to social distancing, or overwhelmed hospitals. Low and middle-income countries may have higher negative impact because of less resilient health systems. Previous studies in Brazil showed a reduction in hospitalizations for cardiovascular diseases (CVD). However, they were restricted to some cities or the first three months of the pandemic. Purpose: Evaluate the impact of COVID-19 pandemic in the number and severity of hospitalizations for CVD in the Brazilian public and universal health system during 2020 and 2021, considering differentials by age, sex, region of the country. Methods: Ecological, time series study analysing the number of hospitalizations, number and proportion of intensive care unit (ICU) admissions and in-hospital deaths for CVD, from epidemiological week (EW) 10/2020 (first confirmed COVID-19 case) to EW 21/2021, using data from the Hospitalization Information System (SIH-SUS). CVD was defined as in Chapter IX from ICD-10. Observed data was compared to the mean for the same EW of 2017-2019. Risk ratios (RiR) were analysed and 95% confidence intervals were calculated. Results: A 16% (RiR 0.84; 95%CI 0.83-0.84) reduction in hospitalizations for CVD was observed in the pandemic period (n = 953,025). However, higher proportion of ICU admissions (RiR 1.09; 95%CI 1.08-1.09), and in-hospital deaths (RiR 1.14; 95%CI 1.14-1.15) revealed greater severity of hospitalized individuals, which may have ocurred due to delayed admissions, or disrupted pathways of care. Two peaks of reductions in hospitalizations were observed, possibly resulting from different drivers: the first, at the beginning of the pandemic, may have resulted from deferred hospitalized treatment, while the second may represent competing demands with COVID-19, resulting in even higher proportion of deaths . Women, older individuals and those living in the least developed North and Northeast regions were mostly negatively impacted, exacerbating vulnerabilities in CVD care. Conclusions: The COVID-19 pandemic disrupted CVD care in Brazil. Health policies must address hospitalizations by CVD during future pandemics, including reorganizing pathways of care, public campaigns about symptoms that require hospitalization, and greater availability of ICU beds, besides a plan to face the rebound effect for deferred procedures. 108357 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Evaluation of Angiographic Patence of the Guilt Artery, in Patients with Acute St-Elevation Myocardial Infarction, using Double Antiplatelet Aggregation MARCOS VINICIUS COELHO DUTRA1, CARLOS ALBERTO KENJI NAKASHIMA1, LILIAN BELINASO1, VIVIANE DE SA PEREIRA1, RICARDO PHILIPE ZAGO1, ANTONIO DEJAIR ACOSTA PAZZINI1, VANESSA DELMIRO DOS SANTOS1, CASSIO PERFETE1, ERASMO SIQUEIRA1, DALTON BERTOLIM PRECOMA1 (1) Hospital Angelina Caron Background: Early reperfusion of the ischemic myocardium is the most important advance in the last 30 years when it comes to acute myocardial infarction (AMI) with ST-segment elevation (STEMI), which can be in the mechanical form by angioplasty, or pharmacologically with use of thrombolytic, respecting the indication of each one. Antiplatelet therapy, from the studies with acetylsalicylic acid as in the Isis-2 study, demonstrating a 23% reduction in mortality when used alone in acute coronary syndrome (ACS), the addition of low molecular weight heparin, to more recent publications with the new adenosine diphosphate blockers and thrombin receptor blockers, corroborating the reduction of outcomes in the acute scenario of post-angioplasty AMI (thrombosis reduction), and making dual antiplatelet aggregation (DAPT) an essential part of the treatment of ACS. Few trials provide us with information comparing whether such medications, used as indicated in STEMI, were able to maintain the patency of the affected vessel pre-coronary angiography. Objective: To compare, between the two groups analyzed (pre-treatment with clopidogrel vs. ticagrelor) the patency of the culprit coronary artery assessed by TIMI angiographic flow analysis by coronary angiography. Methods: A total of 3287 medical records of patients admitted to a chest pain unit of a tertiary hospital in the metropolitan region of Curitiba - Parana were analyzed from March 1, 2019 to March 1, 2021. Of the 3287 patients initially evaluated, 384 patients were selected with a diagnosis of STEMI, 16 patients were excluded due to lack of data in their medical records and 334 patients were analyzed until hospital discharge. Results: Of all the cases that used ticagrelor, 65.1% had occluded vessels and of the cases of clopidogrel, 65.8% of the affected vessels remained occluded. Therefore, no significant difference was found between clopidogrel and ticagrelor regarding the probability of being occluded (p = 0.585). Conclusion: We can conclude that in the analyzed sample, there was no statistical difference between the use of clopidogrel and ticagrelor in the patency of the vessel affected by the occlusion. 108384 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Independent Clinical and Echocardiographic Predictors of Restenosis After Percutaneous Mitral Balloon Commissurotomy Followed for 24 Years RAFAEL ALEXANDRE MENEGUZ MORENO1, Nisia Lira Gomes1, Alfredo Nunes Ferreira-Neto1, Auristela IO Ramos1, Zilda Meneghelo1, J. Italo Franca1, Amanda GMR Sousa1, Sergio Luiz Navarro Braga1, Dimytri Siqueira1, J. Ribamar Costa Jr.1 (1) Instituto Dante Pazzanese de Cardiologia; (2) Universidade Federal de Sergipe; (3) Hospital Primavera Background: Mitral valve stenosis (MVS) is one of the most common structural heart diseases in developing countries, primarily due to rheumatic disease. Percutaneous mitral balloon valvuloplasty (PMBV) has been, since its introduction in 1984, the preferred option of treatment for such disease. However, restenosis is presented with an approximate incidence of 20%. Echocardiographic scoring of the mitral apparatus has been the main tool used to indicate and foresee the possible result of the procedure. The objective of this study was to enlight risk factors of mitral valvular restenosis in a significant number of patients submitted to percutaneous mitral balloon commissurotomy for the treatment of mitral stenosis (MS), particularly when secondary to rheumatic heart disease. Methods: This study reports the vast experience of a single center high volume tertiary institution where 1.794 consecutive patients were treated with PMBC between 1987 and 2011. The primary endpoint was to determine the independent predictors of this untoward event, defined as loss of over 50% of the original increase in maximum valve area (MVA) or MVA < 1.5 cm2. Results: Mitral valve restenosis was observed in 26% of the cases (n = 483). Mean population age was 36 years old, with most patients being female (87%). Mean follow up duration was 4.8 years. At multivariate analysis independent pre-procedural predictors of restenosis were: left atrial diameter (HR: 1.03, 95% ci: 1.01-1.04, p < 0.01), pre procedure maximum gradient (HR: 1.01, 95% ci: 1.00-1.03, p = 0.02) and higher wilkins scores (HR: 1.37, 95% ci: 1.13-1.66, p < 0.01). Conclusion: In the very long term follow-up, mitral valve restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum valve gradient and high Wilkins scores were found to be the only independent predictors of this deleterious event. 108388 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Evaluation of Perioperatory Complications by Bleeding in Kidney Transplantation Patients with Dual Antiplatelet Therapy LILIAN BELINASO1, Camila Richter1, Carlos Gustavo Marmanillo1, Carlos Alberto Kenji Nakashima1, Erasmo Junior Toledo Siqueira1, Dalton Bertolim Precoma1, Marcos Vinicius Coelho Dutra1, Viviane de Sa Pereira1, Luan Gabriel Paese1, Sergio Antonio Lopez1, Romulo de Lima Moreno1, Rodney de Oliveira1 (1) Hospital Angelina Caron - HAC Background: As the prevalent kidney transplant population grows, there is an increasing need to quantify the risk of medical conditions to minimize complications. Bleeding events are a cause of hospitalization and contribute to the morbimortality of these patients. Objective: To evaluate perioperative bleeding complications due to the use of dual antiplatelet therapy (DAPT) in kidney transplantation patients. Methodology: Patients who underwent kidney transplantation between January 2019 and May 2021 were included (n = 372) and divided into 3 groups: control group without antiplatelet therapy (n = 230); patients with perioperative antiplatelet therapy only with acetylsalicylic acid - ASA (n = 123); and patients with perioperative DAPT - ASA and clopidogrel (n = 19). The primary outcome was the rate of bleeding in patients on antiplatelet therapy compared with patients without antiplatelet therapy. Secondary outcomes included location and timing of bleeding, post-bleeding acute myocardial infarction, perioperative transfusion requirement, surgical reintervention, renal explantation, and mortality. Results: Patients with DAPT were a mean age of 59.63 +- 6.94, were more insulin-dependent diabetes and they were all hypertensive (P > 0,002), significantly higher data compared to the other groups. These patients bled significantly more (P > 0.005), mainly at the surgical site (64,7%); 35.3% of the patients required surgical reintervention (p = 0.0013). In this study, most bleeding events (73.6%) occurred within one week after transplantation and 80% required blood transfusion (p = 0,0001). Conclusion: Kidney transplantation can be safely performed without interrupting perioperative ASA therapy and prophylactic anticoagulation. There is an increased risk of bleeding requiring blood transfusion and surgical reintervention when the patient is on DAPT, but without an increase in acute myocardial infarction, renal explantation and short-term mortality. 108408 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Effect of Long-Term Sodium-Glucose Cotransporter 2 Inhibition on Cardiac Remodeling in Rats with Type 1 Diabetes Mellitus EDER ANDERSON RODRIGUES1, Camila Moreno Rosa1, Dijon Henrique Salome De Campos1, Felipe Cesar Damatto1, Gilson Masahiro Murata2, Lidiane Moreira de Souza1, Amanda Bergamo Goncalves de Castro Rego1, Leiliane Rodrigues dos Santos Oliveira1, Patricia Aparecida Borin1, Katashi Okoshi1, Marina Politi Okoshi1 (1) Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil; (2) 2 LIM29, Division of Nephrology, University of Sao Paulo Medical School, Sao Paulo Brazil Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. However, as most clinical trials were performed in type 2 DM, the effects of SGLT2 inhibitors in patients with type 1 DM still need further clarification. In this study, we evaluated the effects of long-term treatment with the SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, and energy metabolism in rats with type 1 DM. Methods: Male Wistar rats were divided into three groups: control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM+DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin; DAPA was added to the rat chow (5 mg/kg/day). Cardiac performance was evaluated by echocardiogram and myocardial function in isolated left ventricular (LV) papillary muscle preparations. Myocardial energy metabolism enzyme activities were evaluated by spectrophotometry. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results: DM+DAPA had lower glycemia than DM [C 112 (108-116); DM 531 (522-535)*; DM+DAPA 267 (179-339) mg/dL; p < 0.05 vs C and DM+DAPA]. Echocardiogram showed that DM and DM+DAPA had left atrium and left ventricle dilatation with systolic and diastolic dysfunction; in DM+DAPA, the changes were attenuated in relation to DM. Developed tension and +dT/dt were higher in DM+DAPA than DM in basal condition. After inotropic stimulation with post-pause contraction, extracellular calcium concentration elevation, and isoproterenol addition to the nutrient solution, +dT/dt and -dT/dt were higher in DM+DAPA than DM. Hexokinase, phosphofructokinase, and pyruvate kinase activity was lower in DM than the C. Phosphofructokinase and pyruvate kinase activity was higher in DM+DAPA than DM. Conclusion: Long-term dapagliflozin treatment attenuates cardiac remodeling and myocardial dysfunction and preserves hexokinase, phosphofructokinase and pyruvate kinase activity in rats with type 1 diabetes mellitus. 108797 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Assessment in Patients with Psoriasis: Comparison of Different Clinical Scores and Their Associations with Subclinical Biomarkers Such as Pulse Wave Velocity and Carotid Intima-Media Thickness - a Pilot Study MARCELA MATTOS SIMOES1, Angelica Navarro de Oliveira3, Ricardo Simoes1, Karina Braga Gomes2, Bruno de Almeida Rezende4, Marcus Vinicius Bolivar Malachias3 (1) Post-Graduate Program in Health Sciences - Faculty of Medical Sciences of Minas Gerais-MG, Belo Horizonte/MG, Brazil; (2) Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte/MG, Brazil; (3) Institute of Hypertension of Minas Gerais, Belo Horizonte/MG, Brazil,; (4) Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte/MG, Brazil Background: Psoriasis is an inflammatory skin disease that can have systemic consequences such as cardiovascular disease (CVD). Objective: To evaluate commonly recommended clinical risk scores and their associations with pulse wave velocity (PWV) and intima-media thickness (IMT), recognized subclinical cardiovascular (CV) biomarkers, in individuals with psoriasis without apparent CVD. Methods: This is a cross-sectional observational pilot study involving 44 male subjects, 11 of whom had moderate to severe psoriasis, according to the Psoriasis Area Severity Index (PASI) > 10 and the Dermatological Quality of Life Index (DLQI) > 10, and 33 healthy subjects (control group). Groups were assessed using the Global Risk Score (GRS), Atherosclerosis Cardiovascular Disease (ASCVD) by Pooled Cohort Equations and the SCORE system, in addition to measurements of PWV and IMT. Comparisons between groups and associations between clinical risk scores and biomarkers measurements were performed considering a significance level of 5%. Results: The psoriasis group (PG) had a higher CV risk estimated by GRS (p = 0.001) and ASCVD (p = 0.025), but not by SCORE (p = 0.289), as well as higher PWV (p = 0.033) compared to the group control (GC). ASCVD (p = 0.014) and SCORE (p = 0.009) were associated with PWV in the psoriasis group. GRS, ASCVD and SCORE showed a positive association with PWV in relation to the total sample. Clinical risk scores showed no significant association with carotid IMT in the psoriasis group. Conclusion: Patients with psoriasis without apparent CVD have a higher cardiovascular risk when evaluated by clinical scores GRS and ASCVD. ASCD and SCORE were associated with subclinical findings such as higher PWV. 108731 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Association between Maximal Aerobic Power, Isometric Muscle Strength and Functional Capacity in Elderly Women LEANDRO BRASIL REGO1, Leandro Brasil Rego1, Rodrigo Villar2, Danilo Salles Bocalini3, Gustavo Allegretti Joao4, Ruth Caldeira Melo1, Bruna Trindade Souza1, Francisco Luciano Pontes Junior1 (1) Laboratorio de Fisiologia do Exercicio e Envelhecimento, Escola de Artes, Ciencias e Humanidades da Universidade de Sao Paulo, Sao Paulo, Brazil; (2) Cardiorespiratory & Physiology of Exercise Research Laboratory, Faculty of Kinesiology and Recreation and Management, University of Manitoba, Winnipeg, Manitoba, Canada; (3) Laboratorio de Fisiologia experimental e Bioquimica, Centro de Educacao fisica e Desporto, Universidade Federal do Espirito Santo, Vitoria, Brazil; (4) Laboratorio de Fisiologia do Exercicio, Faculdades Metropolitanas Unidas, Sao Paulo, Brazil. Sao Paulo, Bra Introduction: Aging is associated with a decline in cardiorespiratory and musculoskeletal systems that may compromise maximum aerobic power and muscle strength, fundamental aspects for the maintenance of functional capacity in the elderly. Objective: To verify the correlation between maximal aerobic power, isometric muscle strength, and functional capacity in elderly women. Methods: The sample consisted of 30 elderly women aged 60 years or more (X = 65.4 SD = 2.8). To determine the maximal aerobic power, we performed ergospirometric test (gas analyzer Metalyzer II, Cortex(r), Germany) on a treadmill (centurion(r) 300) with constant 1% inclination, initial speed of 4 km/h and 1 km/h increases every minute. The maximum strength was evaluated in lower and upper limbs by isometric contraction in a portable dynamometer (Lafayette Instrument Company, USA). The functional capacity was evaluated by the tests: TUG- (Timed Up and Go), TC 10 m (10 m walk) and SLC (Sit and Stand Up Chair). In all tests 3 measurements were taken and the mean was computed. In the statistical analysis, significance was set at 5% and the assumptions of normality, homogeneity, and sphericity were confirmed with the Shapiro-Wilk, Levene, and Mauchly tests, respectively, and parametric techniques were used. Results: There was a positive and strong correlation between peak VO2 (mL/kg/min) vs. lower limb strength (r = 0.62; p = < 0.001); negative and strong correlation between peak VO2 (mL/kg/min) vs. TUG (r = -0.63; p = < 0.001); moderate and negative correlations between peak VO2 (mL/kg/min) vs. TC10 m (r = -0.49 p = 0.005); peak VO2 (mL/kg/min) vs. SLC (r = -0.52 p = 0.003) and between lower limb strength vs. TUG (r = -0.50; p = 0.005); TC10 m (r = -0.50; p = 0.005); SLC (r = -0.48; p = 0.006). The multiple linear regression showed an R2 49.8% of the result of the dependent variable aerobic power and the following values of the independent variables lower limb strength (B = 0.25; p = 0.012) and "TUG" test (B = -2.161; p = 0.008). Conclusions: It was demonstrated a positive correlation of aerobic power with isometric muscle strength (lower limb) and a negative correlation of these variables with performance in functional tests. Furthermore, isometric muscle strength (lower limb) and the TUG test were important predictors of maximal aerobic power. 108420 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Cardiovascular Health Control in the Family Health Strategy GILBERTO ANDRADE TAVARES1, Gilberto Andrade Tavares1, Joathan Borges Ribeiro5, Marcos Antonio Almeida-Santos4, Antonio Carlos Sobral Sousa1, Jose Augusto Soares Barreto-Filho1 (1) Postgraduate Program in Health Sciences, Federal University of Sergipe; (2) Federal University of Sergipe; (3) Rede D'Or Sao Luiz, Hospital Sao Lucas, Division of Cardiology; (4) Tiradentes University; (5) Postgraduate Program in Adult Health Nursing, University of Sao Paulo; (6) Hospital Sirio-Libanes Introduction: In Brazil, the Unified Health System (UHS) regulates public health care and has in the Family Health Strategy (FHS) the main strategy of primary care. In 2010, the American Heart Association (AHA) proposed to check seven cardiovascular health (CVH) metrics, with goal of reducing CVD deaths in the U.S. by 20% until 2020. The results of the FHS regarding the CVH of the Brazilian population are not known. Objective: Evaluate the control of CVH among adult patients assisted by the FHS in the municipality of Aracaju, Sergipe, Brazil. METHODS A cross-sectional study was conducted using the 7 metrics in CVH among patients treated by the FHS. Those metrics being graded at the "ideal", "intermediate" and "poor" level. The variable "CVH control" was dichotomized into "Controlled" (>five metrics at the ideal level) and "Uncontrolled" (<five metrics at the ideal level). Results: In our study, 32.5% were at ideal level. The majority of the sample (62.75%) were at intermediate level. At the poor level, 4.5% was found in the sample. In the multivariate analysis, after adjustments, <45 years of age (RRa 1.61 (IC 95% 1.15-2.28)), females (RRa 2.07 (IC 95% 1.20-3.60)) and following health guidance from family members and neighbors (RRa 1.28 (IC 95% 1.15-2.28)) were associated with "Controlled" CVH. Having a higher number of children reduces the chance of having "Controlled" CVH by up to 9% (RRa 0.91 (IC 95% 0.84-0.95)). Conclusions: We demonstrated that, only 32.5% of the patients had controlled CVH; the adjusted multivariate analysis showed that being under 45 years of age, female and sharing decisions about their health with neighbors and family members are associated with "Controlled" CVH. Having more children reduces this association. 108421 Modality: E-Poster Researcher - Non-case Report Category: NURSING Spatial Distribution of Chronic Chagas Disease in Terms of Clinical Stages in a Reference Service in Northeast Brazil CAROLINA DE ARAUJO MEDEIROS1, Maria Beatriz Araujo Silva3, Andre Luiz Sa de Oliveira4, Maria das Neves Dantas da Silveira Barros1, Maria Elisa Lucena Sales de Melo Assuncao1, Maria da Gloria Aureliano de Melo Cavalcanti1, Tayne Fernanda Lemos da Silva1, Genova Maria de Azevedo Oliveira5, Cristina de Fatima Velloso Carrazzone1, Zulma Maria de Medeiros2, Silvia Marinho Martins1, Wilson de Oliveira Junior1 (1) Ambulatorio de Doenca de Chagas e Insuficiencia Cardiaca-PROCAPE-UPE; (2) Programa de Pos-graduacao em Ciencias da Saude - FCM-UPE; (3) Faculdade de Enfermagem Nossa Senhora das Gracas - FENSG-UPE; (4) Instituto Aggeu Magalhaes, Fundacao Oswaldo Cruz - Recife -PE; (5) Secretaria Estadual de Saude de Pernambuco - PROGRAMA SANAR-SES-PE Introduction: Chronic Chagas disease (CCD), caused by Trypanosoma cruzi. In Brazil, the Northeast Region is one of the endemic areas for CCD. The geoprocessing allows the identification of patterns and trends in spatio-temporal distributions. Objective: To analyze the spatial distribution of CCD in terms of clinical stages in the reference service in the Northeast region of Brazil. Methods: Ecological population-based approach, the unit of analysis being the municipalities where the population with CCD from 2016 to 2018. The State of Pernambuco is composed of 184 municipalities and 05 mesoregions: Metropolitan Region, Zona da Mata, Agreste, Sertao and Sertao do Sao Francisco. The classification used the Clinical stages listed in the "I Latin American Directive for the Diagnosis and Treatment of Chagas Heart Disease" (A, B1,B2,C and D). The analyzed indicator was the average annual rate of occurrence. Results: The 801 chronic cases, the mean age was 62 +- 12.0 years, with a predominance of females (60%). As for the clinical stages classified as A: 22.5%; B1: 43.5%; B2: 8.5% and C: 25.5%. The mean CCD occurrence rates in terms of clinical stages, the respective standard deviation (SD): A: mean = 0.76; SD = 2.1 in Zona da Mata and Sertao; B1: mean = 1.6; SD = 4.4 in Zona da Mata and Sertao; B2: mean = 0.23; SD = 0.82 in Zona da Mata, Sertao and Sertao do Sao Francisco;C: mean = 0.67; SD = 1.27 in Zona da Mata, Agreste Sertao and Sertao do Sao Francisco as shown in the figure. Conclusions: The spatial distribution of CCD showed spatial heterogeneit, there were clusters in two mesoregions in stages A and B1, while in stages B2 and C in 4 mesoregions indicating the persistence of CCD in these areas, requiring priority health surveillance actions and strengthening of the assistance decentralization. 108422 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Cardiovascular Health Monitoring Mobile Phone Application Development GILBERTO ANDRADE TAVARES1, Matheus Henrique Costa Xavier2, Filipe Euclides Gobatto2, Iara Victoria dos Santos Moura2, Virna Anfrizio Souza2, Wictor Hugo De Souza Silva2, Eleonora Ferraris de Gaspare5, Gledson de Carvalho Santos4, Fabio Batista Santos4, Virgilio Antonio Cardoso Faro4, Jose Augusto Soares Barreto-Filho1 (1) Postgraduate Program in Health Sciences, Federal University of Sergipe; (2) Federal University of Sergipe; (3) Rede D'Or Sao Luiz, Hospital Sao Lucas, Division of Cardiology; (4) Tiradentes University; (5) Parma University Introduction: The Cardiovascular Diseases have been the main cause of death in the world with a slow decrease in mortality rates in most countries. In 2010, The American Heart Association (AHA) defined 7 metrics for a Cardiovascular Health in order to reduce Cardiovascular mortality by 20%. The Mobile Health Tools are able to support shared clinical decision making, telemonitoring feedback and improve patient's adherence to medication regimen. Objective: Demonstrate the development and applicability of the application "Cardiovascular Health" for mobile phones according to the parameters defined by The AHA. Method: The method chosen is the User Centered Design, Dart programming language, Flutter framework and Firebase database. The application was developed using Scrum, with 2-week sprints in which tasks were divided into small deliverables in order to avoid rework and make the process more agile. The research team monitored the project closely and decided about what was done by the group. Results: Each parameter considered ideal, evaluated as "Good", following those requirements, will provide the patient 1 mark. If the participant scores between 5 and 7 marks, will be classified as "Good" Cardiovascular Health; if the score is between 3 and 4 marks, the classification will be "Can be improved"; and if the score is null or under 2 marks, it will be defined as "Needs to be improved". Hence, he will have his "Cardiovascular Health" classified, generating PDF reports. Conclusion: The "Cardiovascular Health" application comprises all the components to measure Cardiovascular Health and will be able to provide physicians and other healthcare workers with better decision making about Cardiovascular Health of the treated population. 109090 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Relationship between Heart Attack and Revasculation Procedure Events on Drug Adhesion in Individuals with Heart Diseases: Population Survey in Brazil ROMERO HENRIQUE DE ALMEIDA BARBOSA1, Emerson Silva de Jesus1, Eldys Myler Santos Marinho1, Johnnatas Mikael Lopes1 (1) Universidade Federal do Vale do Sao Francisco Background: Medication adherence is imperative for adequate care of chronic cardiac health conditions due to their disabling and death potential. However, this self-care characteristic does not develop without professional support and may not be homogeneous in the entire population. Objective: To identify the existence of differences in medication adherence in people with a history of acute cardiac events. Methods: Cross-sectional population-based study of the National Health Survey (NHS) in Brazil in 2019. The sample with 90846 interviews in people over 15 years old. Diagnosis of heart disease was given by the presence of heart failure, arrhythmia, angina, history of myocardial infarction. The independent variables were coronary artery bypass graft surgery (yes/no) and myocardial infarction (yes/no). Medication adherence due to cardiac condition was treated as an outcome. Data analyzed by stratifying the prevalence of the outcome and estimating the prevalence ratio, taking into account the complex sampling of participants and a confidence interval of 95%. Results: We identified 4732 (5.1%;4.8-5.3) individuals with some type of heart disease in the NHS, of which 1383 (29.2%;27.0-31.4) reported at least one episode of myocardial infarction. Revascularization was performed in 1483 (28.9%;26.8-31.0) of individuals with heart disease. Approximately one-third of participants with heart disease do not adhere to medication regularly [3284 (31.4%:29.1-33.7)]. However, it is possible to state that individuals who underwent revascularization procedure [1297 (87.9%;85.4-90.0)] have more medication adherence than those who did not undergo. The occurrence of acute myocardial infarction increases the probability of greater adherence to medication by 13.3% in those who underwent revascularization and 27.5% in those who had an infarction and did not undergo revascularization. In relation to individuals with heart disease and without infarction and revascularization events, the probability of adherence is 59.10%. Conclusion: Acute and harmful cardiac events such as myocardial infarction and revascularization seem to be associated with greater medication adherence in this population. This refers to a scenario of low self-care supported by monitoring of cardiac conditions, requiring greater attention and the proposition of mitigating strategies on the part of health professionals. 109088 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence, Outcomes and Costs of Patients with Renal Dysfunction in the Emergency Department of a Specialized Cardiology Hospital FARID SAMAAN1, Louis Nakayama Ohe1, Livia Gambaro1, Renata Viana1, Emmanuel Almeida Burdmann2 (1) Instituto Dante Pazzanese de Cardiologia; (2) Universidade de Sao Paulo Introduction: Chronic kidney disease and acute kidney injury (AKI) are important complications of heart diseases. In developing countries, epidemiological and cost information on the interaction of these conditions are scarce. Objectives: To determine the prevalence, costs and outcomes of patients admitted for acute coronary syndrome (ACS) with renal dysfunction and AKI. Methods: The study was based on a prospective database analysis of patients admitted for ACS to a Brazilian public hospital specialized in cardiology between 7/16/2018 and 12/31/2019. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at hospital admission. Community-acquired and hospital-acquired AKI were defined as a fall and an increase of >=0.3 mg/dl in serum creatinine from baseline, respectively. Results: 1295 of the 1620 patients had a confirmed diagnosis of ACS (median age 64.2 [56.5-70.6] years, 65.4% male, 82.7% had hypertension, 45.5% diabetes and 22.6% renal dysfunction). The imaging diagnosis of ACS was coronary angiography in 84.3% and the treatment was performed by angioplasty, only clinically and by myocardial revascularization in 47.3%, 40.0% and 12.7%, respectively. community-acquired AKI occurred in 43.9% and 2.3% of patients, respectively. Compared with patients admitted with eGFR >=60 ml/min/1.73 m2, those with eGFR <60 were older (70.6 vs. 62.5 years, p < 0.001), had a higher prevalence of hypertension (92.1% vs. 80.0%, p < 0.001) and diabetes mellitus (60.6% vs.54.5%, p = 0.010), had a higher incidence of AKI (65.0% vs. 51.4%, p < 0.001) and higher: median amount reimbursed for hospitalization (1,344 [366-2,103] vs. 1,334 [290-2,018] dollars, p = 0.034), median length of stay (5 [3-10] vs. 4 [2-7] days, p < 0.001), death within 30 days (4.1% vs. 1.4%, p = 0.004) and death within 12 months (9.2% vs. 2.9%, p < 0.001). Patients with AKI, compared to those without this condition, were older (65.6 vs.63.3 years, p = 0.008), had lower eGFR on admission (78.1 ml/min/1.73 m2 vs.86.1 ml/min/1.73 m2, p < 0.001) and greater: median amount reimbursed for hospitalization (1,334 [301-1,865] vs. 1,724 [973-2,549] dollars, p < 0.001), median length of stay (6 [4-13] vs. 3 [2-5] days, p < 0.001) and death within 12 months (4.8% vs. 2.3%, p = 0.032). Conclusions: In patients with ACS at a cardiology referral hospital, renal dysfunction on admission and AKI during hospitalization were frequent and associated with worse clinical and economic outcomes. 108437 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Growth Differentiation Factor-15 is Associated with Greater Severity in Patients with Chronic Heart Failure DIANE XAVIER DE AVILA1, Gustavo Rodolfo Moreira1, Angelo Michele Di Candia1, Victoria Depes Scaramussa1, Najla Cassibi Cavaliere1, Fernanda Turque Martins1, Maisa Passos Vieira1, Humberto Villacorta1 (1) Universidade Federal Fluminense Background: Natriuretic peptides (NP) are the gold standard biomarkers in HF. However, new biomarkers have emerged, with additional effects to NP in relation to prognosis. Growth differentiation factor-15 (GDF-15) is a marker of oxidative stress and inflammation that may contribute to the prognosis of patients with HF. Objectives: We sought to evaluate the distribution of GDF-15 values, the characteristics of patients with high values and the relationship between their values and NT-proBNP in patients with chronic HF. Methods: This was a cross-sectional study of patients with chronic HF who were on guideline-recommended medical therapies. Patients with signs and symptoms of HF and LVEF <50% were included. The dosage of NT-proBNP was performed using the Elecsys(r) system (Roche, Basel, Switzerland) and GDF-15 by the sandwich immunoassay method with monoclonal antibodies (Elecsys(r), Roche, Basel, Switzerland). Patients were grouped according to GDF-15 values above and below the median. Correlation analysis was performed between GDF-15 and other non-normal continuous variables, using the Spearman method. Results: A total of 67 patients were included. Etiology was predominantly non-ischemic, 61.2% were male, with mean age of 61 +- 13 years. The median GDF-15 values were 1413 pg/mL (interquartile range 1044-2554) and NT-proBNP was 759 pg/mL (168-2354). Patients with GDF-15 values above the median had higher creatinine values (1.32 mg/dL [0.85-1.71] vs 0.91 [0.78-1.08], p < 0.001), higher NT-proBNP values (2071 pg/mL [508-5350] vs 463 [87-962], p = 0.001) and lower LV ejection fraction (30% [27-43] vs 45% [30-54], p = 0.08. There was a positive correlation between GDF-15 and NT-proBNP (r = 0.46, p < 0.001), creatinine (r = 0.56, p < 0.001) and left atrial volume (r = 0.32, p = 0.037). Conclusion: Even after adequate treatment, some patients with chronic HF had high levels of GDF-15. GDF-15 identified patients with greater severity. GDF-15 may be a useful tool in the management of HF patients. 108438 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Growth Differentiation Factor-15 is Associated with Severity Parameters in Patients Admitted to the Hospital with Atrial Fibrillation ANGELO MICHELE DI CANDIA1, Diane Xavier de Avila1, Gustavo Rodolfo Moreira1, Humberto Villacorta1 (1) Universidade Federal Fluminense Background: Growth differentiation factor-15 (GDF-15) is a marker of oxidative stress and inflammation and is increased in a number of cardiovascular disorders. Objectives: We sought to assess the relationship of GDF-15 with severity parameters in patients hospitalized with atrial fibrillation (AF). Methods: Fifty hospitalized patients with a primary or secondary diagnosis of AF from two hospitals were included. GDF-15 was measured at baseline, as well as cardiac and inflammatory biomarkers. A comparison of baseline characteristics was performed in groups with high (above median) and low (below median) GDF-15 values. Correlations were made between the GDF-15 and other variables, using the Spearman method. Results: Twenty-nine (58%) patients were male and the mean age was 68.5 +- 17.3 years. Twenty-eight (56%) had permanent AF and 18 (36%) had HF with reduced ejection fraction (LVEF <40%, HFrEF). The median GDF-15 was 2724 pg/mL (interquartile range 1116-5139). Patients with high GDF-15 values were older (77.5 +- 9.7 vs 59 +- 18.5 years, p = 0.0001) and more likely to have hypertension (92.3% vs 70%, p = 0.018) and permanent AF (69.2% vs 37.5%, p = 0.016). They also had higher NT-proBNP values (4006 pg/mL [2156-7023] vs 816 [174-3814], p = 0.0015), creatinine (1.2 [0.95-1.7] vs 1, 0 [0.75-1.15], p = 0.017) and C-reactive protein (3.1 [1.55-7.32] vs 1.25 [0.55-2.45], p = 0.008). GDF-15 was higher in patients with HF (n = 34 [68%]) vs non-HF (3126 [1737-6457] vs 774 [565-4074], p = 0.01). Patients with HFrEF had higher levels of GDF-15 as compared with those with LVEF >40% (3019 [2012-7299] vs 1533 [784-4674], p = 0.05). All risk scores were higher in patients with high GDF-15, namely CHA2DS2-VASC (4.5 +- 1.6 vs 2.9 +- 2.3, p = 0.008), HAS-BLED (2.4 +- 1.3 vs 1.3 +- 1.1, p = 0.0029), ORBIT (3.5 +- 1.5 vs 1.7 +- 1.5, p = 0.0003) and MAGGIC (20.8 +- 12.3 vs 11 +- 11.2, p = 0.006). There was a direct correlation between GDF-15 and NT-proBNP (r = 0.5, p = 0.002), D-dimer (r = 0.52, p = 0.002) and age (r = 0.43, p = 0.002). Conclusion: GDF-15 values were associated with parameters of greater severity in AF. GDF-15 may be useful as a prognostic factor and may possibly aid in the indication of anticoagulation in AF. 108439 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Relationship between Gdf-15, Urinary Sodium and Markers of Renal Function in Patients with Chronic Heart Failure GUSTAVO RODOLFO MOREIRA1, Diane Xavier de Avila1, Angelo Michele Di Candia1, Victoria Depes Scaramussa1, Najla Cassibi Cavaliere1, Maisa Passos Vieira1, Fernanda Turque Martins1, Humberto Villacorta1 (1) Universidade Federal Fluminense Background: Patients with heart failure (HF) often have altered renal function. Urinary sodium is a marker of diuretic resistance and is associated with a worse prognosis in HF. Growth differentiation factor-15 (GDF-15) is a marker of oxidative stress and inflammation and is a prognostic predictor in HF. Objectives: We sought to assess the relationship of GDF-15 with renal function parameters and with urinary sodium in patients with chronic HF. Methods: We undertook a cross-sectional study of patients with HF from specialized outpatient clinic. Patients with signs and symptoms of HF and LVEF <50% were included. An echocardiogram was performed and blood samples were collected, which were frozen for the final study, where the performance of GDF-15 in the prediction of renal outcomes in HF will be evaluated. The dosage of NT-proBNP was performed using the Elecsys(r) system (Roche, Basel, Switzerland) and GDF-15 by the sandwich immunoassay method with monoclonal antibodies (Elecsys(r), Roche, Basel, Switzerland). Analysis of the relationship between GDF-15 and baseline renal parameters was performed. Correlation analysis was performed between GDF-15 and continuous variables, using the Spearman method. Results: Sixty-seven patients were included. The etiologies of HF were hypertension, diabetes mellitus, alcoholic cardiomyopathy and idiopathic cardiomyopathy. Forty-one (61.2%) individuals were male, with a mean age of 61 +- 13 years. Median GDF-15 values were 1413 pg/mL (interquartile range 1044-2554). Patients with GDF-15 values above the median had lower urinary sodium values (88 mEq/L [53-121] vs 112 [76-171], p = 0.06), lower glomerular filtration rate (GFR) (63.9 +- 29.1 vs 91.2 +- 25 mL/min/1.73 m2, p = 0.001) and higher creatinine levels (1.32 mg/dL [0.85-1.71] vs 0 .91 [0.78-1.08], p < 0.001). There was no significant difference in relation to urinary albumin (21 mg/L [7-126] vs 15.1 [5.8-41], p = 0.30). The urinary albumin/creatinine ratio was higher in the group above the median, but did not reach statistical significance (38 mg/g [11-110] vs 12.5 [4.9-29], p = 0.13). There was a direct correlation between GDF-15 and creatinine (r = 0.56, p < 0.001) and an inverse correlation with urinary sodium (r = -0.39, p = 0.005) and with GFR (r = -0.55, p < 0.001). Conclusion: GDF-15 correlated with lower urinary sodium levels and worse kidney function in patients with chronic HF. Future studies should address whether GDF-15 is a predictor of worsening renal function overtime. 108440 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Impact of Cardiovascular Risk Factors and Renal Disease on Outcomes in Patients Hospitalized with COVID-19: An Observational Study from Two Public Hospitals in Brazil DIANE XAVIER DE AVILA1, Ana Luiza Carraro de Souza2, Gabriel Alverca Meyas2, Mayara Cristina Villela Santos2, Jonatas da Costa Mendonca2, Luciene Maria Mendes da Costa2, Beatriz de Paula Sousa2, Maria Victoria Borges de Oliveira2, Julia Correia Cardoso Guimaraes2, Julie Xavier de Avila Guedes3, Ulisses Oliveira de Melo1, Humberto Villacorta2 (1) Hospital Municipal Che Guevara; (2) Universidade Federal Fluminense; (3) Universidade Estacio de Sa Background: Cardiovascular risk factors are prognostic factors in COVID-19 and have been scarcely studied in Brazil. Objectives: To assess the impact of cardiovascular risk factors on the outcomes in patients admitted for COVID-19. Methods: From July 2020 to February 2021, 200 patients from two public hospitals were enrolled. Patients were included if they had: typical symptoms or signs of COVID-19, a positive real-time polymerase chain reaction test (RT-PCR) for COVID-19, and age above 18 years old. This was a prospective, observational, longitudinal study. Data was collected within 24 hours from admission. The primary endpoint was a combination of hospital mortality, mechanical ventilation, hemodialysis or hospital length of stay >28 days. Results: There were 98 (49%) events during the hospital course and 72 (36%) died in the hospital. Patients with a primary endpoint were older and more likely to have a history of hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Vital signs at admission associated with events were diastolic blood pressure, respiratory rate and oxygen saturation in ambient air (O2Sat). Serum creatinine >1.37 mg/dL at admission had sensitivity of 51.6 and specificity of 82% to predict the primary endpoint, with an area under the curve (AUC) of 0.68. In multivariate analysis, age, diabetes, CKD, and COPD were independent predictors of the primary endpoint. Age and CKD were independent predictors of in-hospital mortality. Conclusion: Cardiovascular risk factors, such as diabetes and CKD are related to a worse prognosis in patients hospitalized with COVID-19 in Brazil. 108452 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Remote Monitoring of Pacemakers and Defibrillators - Effective and Safe in Brazil? EDUARDO ARRAIS ROCHA1, Luis Gustavo Bastos Pinho1, Juvencio Santos Nobre1, Maria Eduarda Quidute Arrais Rocha3, Marcela Sobreira Kubrusly2, FernandaPimentel Arrais Maia4, Eduardo Augusto Quidute Arrais Rocha2, Maria Camila Timbo Rocha3, Pedro Barbosa Duarte Vidal1, Vitor Olimpio Coimbra2, Bruna Sobreira Kubrusly1, Ana Rosa Pinto Quidute1 (1) Universidade Federal do Ceara; (2) Universidade Unichristus; (3) Universidade de Fortaleza - UNIFOR; (4) Universidade Federal do Ceara - Campos Sobral Introduction: The remote monitoring (RM) of Implantable electronic cardiac devices (IECD) has become a common follow-up modality in many countries given its effectiveness, safety, facilities for the patient and possibilities of early interventions. In Brazil, however, this form of follow-up is an exception. This work aims to demonstrate the findings, evolution and peculiarities of IECD follow-up in a tertiary center in Brazil. Methods: This is a cohort, prospective study, involving 119 patients, followed in room office visit at 6 months interval with daily RM, with mean age 72 +- 14.2, ejection fraction 55% (34.5/57%), 57.1% in functional class >=II, 30.2% with pacemakers (PM), 42.8% with defibrillators (D), 3.3% with biventricular pacemaker (CRT) and 22.7% with CRT-D. The logistic regression was used to obtain evidences that the RM is associated with the following outcomes: immediate changes in therapy, elective changes in therapy and avoidance of hospitalizations. Results: Events were detected in 63.9% of the cases in 29.5 +- 23 months of follow-up; 16% presented more than 6 events; 36.1% no events and 27.7% had more than one event detected. The most common events were: 18.5% with alterations in the electrode/battery or in the thoracic impedance parameters; 33.6% with ventricular arrhythmia and 44.5% with supra-ventricular arrhythmias. It was observed that 86.5% of patients and 91.6% of physicians reported feeling secure with this method of follow-up. The outcomes found were: 23.5% needed immediate changes in therapy, while 44.5% needed elective changes. The RM was important to the beginning or maintaining of the anticoagulation in 16.9% and avoided hospitalization in 19.3%. Through the use of logistic regression, there are evidences that the RM had an statistically significant impact in the elective changes of conduct (p = 0.03), immediate changes of conduct (p = 0.007) and reduced hospitalization (p = 0.04). Conclusion: The RM was considered effective and safe in the following-up of patients with IECD in some regions of Brazil. This method of follow-up allowed for many early interventions or electives ones which made therapeutic handling and increased safety of the patients. 108459 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Potential Clinical Relevance of Left Atrial Strain in the Identification of Undetermined Diastolic Dysfunction in Patients with Chronic Kidney Disease Under Conservative Treatment JAIME AFONSO SOUSA NETTO1, Arise Garcia de Siqueira Galil1, Andre Pereira Duque Estrada2, Marcus Gomes Bastos1 (1) Universidade Federal de Juiz de Fora-UFJF; (2) Universidade Federal Fluminense-UFF Background: Half of the patients with heart failure (HF) have diastolic dysfunction (DD) and a preserved left ventricular ejection fraction (LVEF). The indexed left atrial volume (ILAV) is one of the main components in the assessment of DD. However, there are controversies regarding the use of the left atrial strain (LAE) to assess DD. Objectives: To evaluate the use of LAE in the identification of indeterminate diastolic dysfunction (IDD) not detected by ILAV, in patients with chronic kidney disease (CKD) stages 3B to 5 in conservative treatment and LVEF. Methods: Prospective cross-sectional study that evaluated 114 patients with CKD stages 3B to 5 under conservative treatment and who presented LVEF through transthoracic echocardiography (TTE). The patients were divided into two groups, with and without left ventricular hypertrophy (LVH). The analysis of the strain of the left atrium was evaluated by the speckle tracking method from the apical section of 2 and 4 chambers, evaluating the deformation curves of the left atrium (LA). Results: LAE increased the detection of DD in the group with LVH (p < 0.01). The mean glomerular filtration rate (GFR) (in mL/min/1.73 m2) in patients with and without LVH was 32.6 +- 11.9 and 40.4 +- 13.9, respectively (p < 0.05). The LAE found was lower in the LVH group 20.3 +- 5.11 vs 26.1 +- 9.1, (p < 0.05). Conclusion: In patients with non-dialysis CKD stages 3B to 5 with LVH and LVEF, in the studied sample, the use of LAE potentially increases the identification of indeterminate cases of DD. 108717 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Influence of Type 2 Diabetes Mellitus on Mortality from Congestive Heart Failure Due to Chagas Disease in Women and Men ANTONIO DE PADUA MANSUR1, Carlos Henrique Del Carlo1, Jose Antonio Ramos Neto1, Andre Barbosa de Abreu1, Airton Roberto Scipioni1, Antonio Carlos Pereira Barretto1 (1) Insituto do Coracao - HC FMUSP Background: Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of congestive heart failure (CHF) in Brazil and carries high morbidity and mortality. Type 2 diabetes mellitus (T2DM) is associated with a higher cardiovascular risk in women than men. This study aimed to analyze the influence of T2DM on CHF mortality from CCC in women and men. Methods: From February 2017 to September 2020, we followed CCC's cohort of outpatients with CHF (Framingham criteria). Specific serological tests diagnosed Chagas disease. Baseline data included clinical features and echocardiographic findings. Statistical analyzes used the Kaplan-Meier method for time-to-event data and Cox proportional hazards methods to look for predictors of death. Results: We studied 733 patients mean age of 61.4 +- 12.3 years, 381 (52%) were male. T2DM was present in 46 (15%) women and 40 (12%) men. Women with T2DM, compared to men with T2DM, had a higher mean age (62.7 +- 12 vs. 59.7 +- 12.5 years; p < 0.001), had a higher mean left ventricular ejection fraction (LVEF) (42.8 +- 14.3% vs. 37.3 +- 14.3%; p < 0.001) and a smaller left ventricular diastolic diameter (58.2 +- 8.5 vs. 61.9 +- 8 .6 mm; p < 0.001). Over a 3-year follow-up period, 26 (65%) men and 30 (65.2%) women with T2DM died, and mortality were higher in T2DM patients compared to nondiabetics . Cox regression adjusted for age, previous myocardial infarction, T2DM, previous stroke, chronic kidney disease (CKD), atrial fibrillation (AF), and LVEF showed, in descending order, T2DM (HR = 2). .19), stroke (HR = 1.81), AF (HR = 1.80), CKD (HR = 1.72), and reduced LVEF (HR = 1.29) as the most important predictors of death in women and, in men, stroke (HR =), DM2 (HR = 2.01), CKD (HR = 1.83), AF (HR = 1.58) and reduced LVEF (HR = 1.24). Conclusions: CHF mortality from CCC was similar in women and men with T2DM. T2DM neutralized the protection of women compared to men concerning mortality from CHF. 108719 Modality: E-Poster Researcher - Non-case Report Category: NURSING Quality of Life and Depression in Patients with Heart Failure LEANDRO LOUREIRO BUZATTO1, Tarsila Perez Mota1, Leticia de Lana Pereira1, Mayumi Alves Hayafugi1, Daisa de Mesquita Escobosa1, Marina Barros de Melo1, Carolina Ivo de Araujo1, Carla Manuela Pereira de Araujo1, Marcelo Franken1 (1) Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein Introduction: The adaptations and changes in the lifestyle of patients with heart failure (HF) is the main reason why the quality of life of these individuals becomes fragile. Studies show the high prevalence of depression and associate this condition directly with HF. The relationship between changes in quality of life, the occurrence of depression and the presence of HF result in unfavorable outcomes for the patient, justifying the performance of the present study. Objective: Identify factors associated with quality of life and depression in patients with heart failure. Method: This is a descriptive exploratory cross-sectional study, in patients aged over 18 years, hospitalized with a diagnosis of systolic HF and who had a recent hospitalization between the period March 2017 to December 2020. Patient Health Questionnaire (PHQ2) and Kansas City Cardiomyopathy Questionnaire (KCCQ-12) were administered 30 days after discharge by telephone contact. The analysis considered the relationship between the scores of both questionnaires and the following variables: gender, diagnosis, functional class, previous atrial fibrillation, previous diabetes, previous acute myocardial infarction and previous arterial hypertension. Conclusions: Female patients with heart failure showed a greater association with the depression outcome (p = 0.001) and the reduction in quality of life showed a decline once associated with diagnosis, functional class and age. 108484 Modality: E-Poster Researcher - Non-case Report Category: NURSING A Transition Program is Effective in Improving Adolescents' Knowledge about their Congenital Heart Disease: The Stepstones-CHD Trial EWA-LENA BRATT1, Mariela Acuna Mora1, Carina Sparud-Lundin1, Sandra Skogby1, Asa Burstrom2, Markus Saarijarvi1, Katrina Hanseus3, Annika Rydberg4, Shalan Fadl5, Eva Fernlund6, Kalliopi Kazamia7, Philip Moons8 (1) Institute of health and care science, University of Gothenburg, Sweden; (2) Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden; (3) Department of Pediatric Cardiology, Children's Heart Center, Skane University Hospital, Lund, Sweden; (4) Department of Clinical Sciences, Umea University, Umea, Sweden; (5) Department of Paediatrics, Orebro University Hospital, Orebro, Sweden; (6) Department of Clinical and Experimental Medicine, Linkoping University, Division of Pediatrics, Crown Princess Victoria Children's Hospital, Linkoping University Hospital, Linkoping, Sweden; (7) Children's Heart Center Stockholm-Uppsala, Karolinska University Hospital and Akademiska University Hospital, Sweden; (8) KU Leuven, Department of Public Health and Primary Care, Leuven, Belgium Introduction: Adolescents with congenital heart disease (CHD) need to acquire knowledge about their heart disease and treatment. This is fundamental for them to implement health promoting behaviors and know how to manage their CHD. Amongst other things, transition programs aim to equip adolescents with this knowledge. However, evidence on the effectiveness of such interventions is limited. Objective: To investigate if a transition program is effective in improving disease-related knowledge of adolescents with CHD. Methods: The STEPSTONES (Swedish Transition Effects Project Supporting Teenagers with chrONic mEdical conditionS) transition program is an 8 components intervention. The central component was a transition coordinator (specialized nurse) who had three consultations with the participants during a 2y period. A randomized controlled trial (RCT) was conducted in two CHD centers in Sweden. Participants were randomly assigned to the intervention (IG; n = 70) or control group (CG; n = 69). Knowledge was measured at the age of 16 y (T0; baseline), 17y (T1) and 18.5y (T2) using the Knowledge Scale for Adults with Congenitally Malformed Hearts questionnaire, psychometric evidence supported its validity and reliability. The total score ranges from 0-7, with higher scores denoting a higher CHD-related knowledge. Change in score between T0 and T2 was analyzed using Fisher's non-parametric permutation test unadjusted between the two groups. Analyses were performed on the Full Analysis Set (FAS). Results: In total, 114 participants were included in the FAS, of which 54 were in the IG and 60 in the CG. At baseline, the mean knowledge score in the IG was significantly lower (3.7 +- 1.6) than in the CG (4.4 +- 1.5) (p = 0.03). At T2, the knowledge score was significantly higher in the IG (5.0 +- 1.3) than in the CG (4.5 +- 1.5) (p = 0.045). In line with this, the change over time (T0-T2; 2.5y) was significantly different between the two groups (Mean difference = 1.22; 95%CI = 0.60-1.82; p = 0.0002). The effect size was 0.74, indicating a moderately large effect. Conclusion: This RCT showed that the STEPSTONES transition program was effective in increasing disease-related knowledge in adolescents with CHD, which is an important aspect in preparing them for the transition to adulthood and the transfer to adult care. 108485 Modality: E-Poster Researcher - Non-case Report Category: CARDIO-ONCOLOGY 18F-FDG PET/CT in the Early Diagnosis of Cardiotoxicity: Evaluation of the Best Site to Obtain the Cardiac SUV Index DIEGO RAFAEL FREITAS BERENGUER1, Gustavo Freitas Alves de Arruda1, Mayara Lais Coelho Dourado1, Felipe Alves Mourato2, Monica de Moraes Chaves Becker1, Roberto de Oliveira Buril1, Brivaldo Markman Filho1, Simone Cristina Soares Brandao1 (1) Universidade Federal de Pernambuco (UFPE); (2) Real Hospital Portugues de Beneficiencia em Pernambuco Objective: To evaluate the behavior of the standardized uptake value (SUV) of the radiopharmaceutical 18F-FDG before, during and after chemotherapy (QT) at different cardiac sites, as well as to measure the degree of reproducibility for the method in the context of cancer treatment follow-up. Materials and Methods: Retrospective cohort including lymphoma patients who underwent 18F-FDG PET/CT before, during and/or after chemotherapy. The uptake behavior through the mean and maximum SUVs was evaluated in four cardiac sites and in control sites in the aorta and liver. Twenty exams were randomized for reproducibility analysis by two examiners who were blinded to each other's results. Each one of them did the evaluation in a second moment to elucidate the intra-observer reproducibility. Results: A significant increase in SUVs was observed in all cardiac sites in the interim and final moments (post-terminus of QT) when compared with pre-QT SUVs. The left ventricular (LV) free wall was the cardiac region with the greatest increase in 18F-FDG uptake . As for the reproducibility, it was possible to verify substantial results for the reliability of the measurement of SUVs, both intra and inter-observer . Conclusions: 18F-FDG Cardiac uptake increased along QT, with the LV free wall being the site with the greatest increase. The reproducibility analysis showed high inter-observer correlation values. 108487 Modality: E-Poster Researcher - Non-case Report Category: NUTRITION Investigating Perception on Obesity for Prevention of Cardiovascular Diseases RAMPHUL YOGESHWAREE1, Chan Sun Marie France1, Cheeneebash Jayrani1 (1) University of Mauritius, Faculty of Medicine and Health Sciences Introduction: In Mauritius, a rapidly developing island in the Indian Ocean, 89% of the deaths are due to non-communicable diseases, out of which 33% are caused by Cardiovascular Diseases. With the prevalence of obesity which has increased from 10.3% in 2004 to 19.1% in 2015, cardiovascular complications linked to obesity are expected to increase, based on the well-established relationship between obesity and cardiovascular diseases. Objective: This study investigated the perception on obesity of Mauritian police officers for tailor-made health interventions. No such study had previously been conducted in Mauritius. Methods: This cross-sectional study was carried out using a pre-tested survey instrument, based on the Health Belief Model with obesity-related questions pertaining to participants' perceived susceptibility, severity, barriers, benefits, cues to action and self-efficacy. The study population consisted of random sample police officers, with the calculated sample size being 384. Ethical clearance was obtained from the relevant research ethics committee. Results: There were 384 respondents, consisting of 240 men (62.5%), and 144 women (37.5%) with age span from 18 to 59, 77.3% of the study population being in the age group 26 to 50. The participants' mean score on the perceived severity scale was 3.8 out of five points (+-1.2), while their mean score on the perceived susceptibility scale was 3.0 out of five points (+-1.2). A stepwise multiple regression analysis showed that the susceptibility score (dependent variable) and sex, age, ethnicity, socioeconomic position and alcohol (independent variables) were significant at 95% confidence interval. Discussion: The lower mean susceptibility score among women as compared to men and among those who are overweight/obese as compared to those with normal Body Mass Index is of great concern. The findings of this study need to be the basis for the development of customized health interventions for the primary prevention of cardiovascular diseases. The vulnerability of women to cardiovascular diseases needs to be emphasized to make women more cautious on their health. Conclusions: In light of the findings of this study, we recommend primary prevention with integrated approach for promotion of healthy eating and physical activities, with a particular focus on women who need to be sensitized on their vulnerability to cardiovascular diseases. 108490 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Prognostic Impact of Right Ventricular Dysfunction After Acute Decompensated Heart Failure. the Forgotten Ventricle BRUNO REZNIK WAJSBROT1, Ana Luiza Ferreira Sales1, Andre Luis Sales Feitosa1, Carolina Pereira de Barros1, Felipe Neves de Albuquerque1, Marcelo Imbroinise Bittencourt1, Pedro Pimenta de Mello Spineti1, Roberto Esporcatte1, Denilson Campos de Albuquerque1, Ricardo Mourilhe-Rocha1 (1) State University of Rio de Janeiro - Pedro Ernesto University Hospital Introduction: Right Ventricle (RV) failure is found in as many as fifty percent of heart failure (HF) patients. Echocardiographic parameters are studied with the aim of refining prognosis of HF, but isolated prognostic impact of the "forgotten ventricle" is not often studied. Purpose: The objective of this study is to define echocardiographic parameters associated with post-discharge mortality after admission for ADHF. Methods: This is a study in a single center, transversal, cohort of hospitalized patients with ADHF, aged >18 years, conducted at a University Hospital in Brazil. Data was collected from September 2019 to September 2021. Patients in renal replacement therapy before admission or with cancer in palliative care were excluded. Continuous variables were analyzed with Mann-Whitney U test, categorical variables with log-Rank test. Analysis was made using SPSS software. Results: A total of 200 patients were enrolled. The mean age was 62 years (SD +- 14.5), 65.9% male, 63% with hypertension, 29.1% with diabetes and 32.8% with ischemic heart disease (IHD). Three month and a year mortality was respectively 8.4% and 39.5%. HFrEF was observed in 67.2%, 14.4% HFmrEF and 18.4% HFpEF. Severe mitral regurgitation (MR) was observed in 22.5% RV dysfunction in 47%. Median ejection fraction, end-systolic (ESD), end-diastolic diameter (EDD) and systolic pulmonary arterial pressure (sPAP) was respectively 33% (24-45.5), 49 mm (38.25-56), 59 mm (52-65) and 44.5 mmHg (32.75-57.25). Only RV dysfunction was associated with reduced long-term mortality (p = 0.038). Average follow-up time was 459 days. Conclusion: RV disfunction has an isolated prognostic impact on long term survival after admission for ADHF. Trials that focus on therapies for RV function might reduce mortality for HF patients. 108496 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Efficacy of Patient Blood Conservation Strategies and Reduction of Plasma Transfusions and Their Complications in Coronary Artery Bypass Graft Surgery ANTONIO ALCEU DOS SANTOS1, Gilmara Silveira da Silva2, Flavia Cortez Colosimo Bastos2, Jose Francisco Baumgratz2, Jose Pedro da Silva2, Luciana da Fonseca da Silva2, Rodrigo Moreira Castro2, Rodrigo Freire Bezerra2, Carlos Eduardo Panfilio1, Isabel Cristina Cespedes1 (1) Escola Paulista de Medicina - Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil; (2) A Beneficencia Portuguesa de Sao Paulo Hospital, Sao Paulo, Brazil (BP-SP) Introduction: Allogeneic blood is an increasingly scarce resource in blood banks around the world due to its increasing demand . Cardiac surgeries represent an excessive consumption of hemocomponents . Plasma transfusions are associated with more risks than benefits . The rational use of allogeneic blood has become a worldwide necessity, aiming to reduce morbidity and mortality and hospital costs [5-7]. Hence the importance of scientific educational measures, encouraging procedures, techniques, and drugs to reduce allogeneic blood transfusions in coronary artery bypass graft surgery (CABG). Objective: To verify whether clinical and surgical strategies for conserving the patient's own blood are effective in reducing plasma transfusions and their complications in CABG. Methods: Retrospective cohort study of patients undergoing CABG. A total of 4923 patients were studied from a database, 3010 patients from the year 2010 (group 1) and another 1913 patients from the year 2012 (group 2). For one year and six months, biweekly multidisciplinary meetings were held for scientific updates on transfusion practices, focusing on learning and implementing patient blood conservation strategies, based on two main pillars: 1. Reduction of blood loss (meticulous hemostasis and optimal use of antifibrinolytics); 2. Optimization of physiological tolerance to anemia (supplementary oxygen therapy, more restrictive transfusion management, treating anemia). After these educational measures to conserve the patient's blood, a new data collection was carried out for a comparative analysis of the variables of group 1 and 2. Results: A total of 377 patients received plasma transfusions, with a significant reduction from 13.1% (282 patients) in group 1 to 6.7% (95 patients) in group 2, p < 0.001. There was also a significant reduction in infection (mediastinitis) from 3.0% (group 1) to 1.4% (group 2), p < 0.05. There was no difference in the total length of hospital stay and intensive care unit stay in the two groups. The mortality expected by the Euroscore (2.35 vs 2.44, p = 0.215, groups 1 and 2, respectively) in the preoperative period of the patients showed no significant difference in both groups. Conclusion: Patient blood conservation strategies focused on reducing blood loss and optimizing physiological tolerance to anemia resulted in reduced plasma transfusions and postoperative mediastinitis-like complications in patients undergoing coronary artery bypass graft surgery. 108503 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID-19 Pandemic on Coronary Angioplasties in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Introduction: Coronary artery disease represents one of the main causes of death in Brazil and worldwide. Rapid diagnosis is important for effective treatment. The difficulty of accessing referral medical centers during the COVID 19 pandemic influenced the management of these diseases. Coronary angioplasty (CA) as an option for the management of patients with coronary disease was also impacted during this period. The present study aimed to evaluate the influence of COVID-19 on coronary angioplasties in Brazil. Method: We used the database from the Department of Informatics of the Brazilian Health System (DATASUS) through the website We evaluated the number of hospitalizations, deaths, costs and length of stay of patients undergoing CA in Brazil and their relationship with the beginning of the COVID-19 pandemic in Brazil (in 2020) based on data from 2018 to 2021. Results: From January 2018 to December 2021, 302572 patients were hospitalized for CA with stent in Brazil with an annual mean of 75643 +- 4742. Meanwhile, 43870 were hospitalized for primary angioplasty with an annual mean of 10968 +- 278. There was an 8.5% decrease in CA averages for the years before the beginning of the pandemic compared to after the beginning of the pandemic, from 79022 +- 4214 to 72264 +- 2008 (p = 0.177). The mean number of primary angioplasty also decreased (1.8%) from 11067 +- 287 to 10868 +- 332 (p = 0.587). Despite the decrease in the number of angioplasties, there was a 13% increase in the mortality rate in this period in CA from 4.3 +- 0 to 4.9 +- 0 (p = 0.013). In cases of primary angioplasty, there was a 4.5% decrease from 6.8 +- 0.1 to 6.5 +- 0.2 (p = 0.200). The mean hospital stay was 8.5% shorter in CA (p = 0.069) and 8% (p = 0.057) in primary angioplasty. Regarding the costs (in brazilian reais) per hospitalization, there was a slight increase both in CA with 1.6% (p = 0.137) and primary angioplasty with 1.3% (p = 0.133). Conclusion: In the context of the COVID-19 pandemic, hospitalizations for CA and primary angioplasty decreased by 8.5% and 1.8%, respectively, comparing the period before the beginning of the COVID-19 pandemic and after. However, we observed a 13% increase in CA mortality rates over the same period while a 4.5% decrease in primary angioplasty rates. The average hospital stay decreased by about 8% for both PTCA and primary angioplasty while costs increased slightly in both cases. 108501 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID19 Pandemic on Coronary Artery Bypass Graft (CABG) Surgery in Brazil AUREO DO CARMO FILHO1, Rogerio Gomes Fleury1 (1) Hospital Universitario Gaffree e Guinle - UNIRIO/EBSERH Introduction: Coronary artery disease represents one of the main causes of death in Brazil and in the world, whose diagnosis and treatment often require speed and appropriate technologies. The difficulty of accessing health systems during the COVID19 pandemic influenced this entire process. Myocardial revascularization surgery (CABG), one of the options for the management of patients with coronary artery disease, was also impacted during this period. The present study aimed to assess the influence of COVID-19 on (CABG) in Brazil. Method: We used the database from the Department of Informatics of the Brazilian Health System (DATASUS) through the website We evaluated the number of hospitalizations, deaths, costs and length of stay of patients undergoing CABG using cardiopulmonary bypass (CPB) in Brazil and their relationship with the beginning of the COVID-19 pandemic in Brazil (2020) based on data from 2018 to 2021. Results: From January 2018 to December 2021, 65827 patients were hospitalized for CABG with CPB in Brazil. There was a decrease in these surgeries from 18987 in 2018 and 19272 in 2019 to 14641 and 12927 in 2020 and 2021 respectively. Surgery averages for the years before the beginning of the pandemic dropped 27.9% compared to after the beginning of the pandemic, from 19130 +- 201 to 13784 +- 1211 (p = 0.025). Despite the drop in the number of surgeries, there was an 8.8% increase in the mortality rate in this period, from 11.9 +- 1.3 to 12.9 +- 0.6 (p = 0.405). The mean hospital stay was slightly shorter (6.5%), with 25.9 +- 0.6 days in 2018-19 and 24.2 +- 0 days in 2020-21 (p = 0.064). Regarding costs (in brazilian reais) per hospitalization, there was a slight increase (1.2%) from 26332 +- 353 to 26655 +- 131. (p = 0.350). Conclusion: In the context of the COVID-19 pandemic, hospitalizations for CABG with CPB decreased by almost 30% when compared to the period before the beginning of the COVID19 pandemic and after. However, we observed an 8% increase in mortality rates in the same period associated with a slight increase in hospitalization costs. The length of hospital stay remained similar. 108521 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Distal Transradial Access as the Route of Choice for Primary Percutaneous Coronary Intervention in a Large Cohort of Patients in a Real-World Registry MARCOS DANILLO PEIXOTO OLIVEIRA1, Lelio Lemos Pinto Neto1, Ednelson Navarro2, Adriano Caixeta1 (1) Universidade Federal de Sao Paulo, UNIFESP; (2) Hospital Regional do Vale do Praiba The ANGIE (Anatomical sNuffbox for Coronary anGiography and IntervEntions) randomized study compared efficacy and safety between distal transradial (dTRA) and right conventional transradial (cTRA) approaches, observing an association of dTRA with a 2-fold lower risk of occlusion of the proximal radial artery on Doppler ultrasound at 60 days. The dTRA, however, resulted in a 4-fold higher access crossover rate (21.8% vs 5.5%), mainly due to failure to insert the guidewire, as well as longer times to obtain access and perform the procedure. (dTRA vs cTRA: 120 vs 75s and 14 vs 11min, respectively), in addition to a higher radiation area-dose product (~10%). It is therefore questioned whether such limitations associated with the dTRA could impact its incorporation into the primary PCI, which must be performed in a timely manner and by experienced operators. default approach for Coronary Angiography and IntervenTIONs, eventosclinicos.gov.br Identifier: RBR-7nzxkm), among 3,991 patients consecutively submitted to coronary angiography (89%) and/or PCI (60.3%) via dTRA (80.1% by dTRA right), 917 (23%) were due to STEMI. In this subgroup, there were only 17 (2%) access crossovers (failure to insert the sheath wire), 4 of them made possible by contralateral dTRA. Thus, despite the retrospective nature and potential selection biases not documented in this series, it seems to us to be feasible and safe to incorporate dTRA as the route of choice for primary PCI in patients with STEMI. Large randomized trials are still needed and expected to assess the limitations and advantages of this potentially disruptive technique in such a challenging scenario. 108540 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Cardiovascular Risk and Mental Status of Students and Staff at a Public University: Cross-Sectional Study ISABEL CRISTINA SILVA SOUSA1, Brunnella Alcantara Chagas de Freitas1, Kelvin Oliveira Rocha1, Luciana Moreira Lima1 (1) Universidade Federal de Vicosa - UFV Introduction: Mental stress, represented by disorders such as anxiety and depression, has figured in the current scenario, along with modifiable and non-modifiable risk factors, as a risk factor for cardiovascular diseases (CVD). Objective: To describe the global cardiovascular risk and mental status of students and employees at a public university. Methods: This is an observational, descriptive study, whose sample consisted of students, teachers, and staff, aged 18 or over, of both sexes. Data collection was conducted during the months of August and September 2021, using an online questionnaire contemplating the data necessary to calculate the global cardiovascular risk by the Framingham Score and by three instruments of screening of the metal status: Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Self-Reporting Questionnaire (SQR-20). Results: A total of 247 individuals participated in the study, 171 (69.2%) were female and 76 (30.8%) were male. Regarding age, 120 (48.6%) were under 30 years old, 118 (47.8%) were between 30 and 60 and 9 (3.6%) were over 60 years old. There were 157 (63.3%) students, 49 (19.8) professors and 41 (16.6%) staffs. Female participants had a lower 10-year risk of developing CVD (p < 0.001), higher scores for anxiety (p < 0.001), depression (p < 0.001), and mental distress (p < 0.001) when compared to male participants. In the stratification by age group, dichotomizing by gender, individuals younger than 30 also had a lower risk of developing CVD in 10 years (p < 0.001), higher anxiety scores (p = 0.003), depression (p = 0.007), and mental distress (p = 0.004) when compared with participants aged 30 years or older, regardless of gender. The parameters age, body mass index, total cholesterol, LDL, and triglycerides were significantly higher in professors and staff when compared to students (p < 0.01). However, significantly higher scores of depression, anxiety, and mental distress were observed in students when compared to staff and professors (p < 0.001). In addition, the group of professors had a higher risk of CVD in 10 years than staff and students (p < 0.001). Conclusions: Women have higher scores for mental health disorders compared to men. The younger the age, the higher the scores for mood disorders, anxiety, and mental distress, regardless of sex. The 10-year CVD risk was not correlated with mental health markers in the sample studied. 108584 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH A Lifetime Hazard Analysis on the Interaction between Comisa and Cardiometabolic Disorders MIGUEL MEIRA E CRUZ1, Cristina Salles2, David Gozal4, Jose Fausto Pinto5, Isabel Rocha3 (1) Centro Europeu do Sono; Sleep Unit, Centro Cardiovascular da Universidade de Lisboa, Lisbon, Portugal; (2) International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Brazil; (3) Cardiovascular Autonomic Function Lab, Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal; (4) University of Missouri, Columbia, United States; (5) Dpt Coracao e Vasos, Centro Hospitalar Universitario de Lisboa Norte, CAML, CCUL, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal Introduction: While the associations between Sleep Apnea and cardiovascular and metabolic dysfunction are now well established, the interactions between insomnia and cardiometabolic disturbances are less well understood. Notwithstanding, when both sleep disorders occur as in COMISA patients, it is possible that the morbid consequences will be exacerbated, albeit while displaying age and sex dependencies. We therefore examined 3 groups of COMISA patients of markedly different ages to assess whether the presence of COMISA interacts differentially with cardiovascular risk during the lifespan. Methodology: A total of 850 patients were enrolled in this study: Pediatric (n = 50; ages ranging from 9 to 19 years), Adult (n = 685; 31-60 years) and Elderly (n = 115; >=65 years). Obstructive Sleep Apnea and Insomnia were assessed with validated age-adjusted questionnaires for each group and high-risk COMISA was established when high risk for OSA as well as high risk for Insomnia were present. Results: Among the Pediatric cohort (58% males), 9 (18%) subjects were high-risk for COMISA (age was 13.6 +- 3.3 years; BMI of 23.0 +- 6.9 Kg/m2). Neither hypertension nor CVD were present in this age group; 28% were obese (BMI >95% for age), 11.1% consumed alcohol regularly and 54.4% were sedentary (no physical activity). In the Adult cohort, 25.3% were high-risk for COMISA (49.8 +- 13.8 years; BMI of 31 +- 6.3 Kg/m2). 76.5% were hypertensive or reporting cardiovascular disease, 13.3% were diabetic and 60.3% were sedentary, 8.4% were cigarette smokers, and 46.9% consumed alcohol regularly. Of the Elderly cohort, 22.6% of patients (11 males, 42.3%) were with high risk for COMISA. Their mean age was 70.6 +- 6.6 years and BMI of 28.7 +- 5.1 Kg/m2, with 61.5% being hypertensive or reporting the presence of cardiovascular disease, 21% were diabetic, 65,4% were sedentary and 7.7% were cigarrete smokers. Conclusions: The presence of high risk COMISA is frequent across all ages and may confer increased risk for cardiovascular and metabolic disorders, particularly after reaching adulthood and beyond. It is likely that both the sedentary lifestyle, and alcohol consumption may contribute to this risk, but the presence of COMISA may add an additional risk factor for cardiometabolic complications. Further research is needed to explore how the concurrent presence of Sleep Apnea and Insomnia exacerbates cardiovascular and metabolic risk in larger clinical populations subjected to more precise diagnostic methods. 108589 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Diagnostic Properties of Diagonal Ear Lobe Crease in Coronary Artery Disease SERGIO LUIZ ZIMMERMANN1, Sergio Luiz Zimmermann1, Leonardo Campanelli Steinhausen2, Bruno Luiz Mueller2 (1) Hospital Santa Isabel, Blumenau; (2) Universidade Regional de Blumenau Background: Coronary angiography is the most accurate method for diagnosing coronary heart disease, but it envolves exposure to radiocontrast agents and radiation, which can increase morbidity and mortality. Thus, it is necessary to study additional markers to identify of coronary artery disease (CAD), such as the diagonal ear lobe crease (DELC). Objectives: To determine DELC's diagnostic properties in the identification of coronary disease and its association with comorbidities. Methods: A cross-sectional study with 278 patients over 18 years old, who underwent coronary angiography performed by at least 1 of 2 interventional cardiologists. The presence and absence of PLL and associated comorbidities was determined by two trained examiners. Results: PLL was only associated with older age (p < 0.05). PLL had a sensitivity of 76.2%, a specificity of 17.6% in the identification of CAD and an overall accuracy of 58.3%. Conclusion: We concluded that the diagnostic accuracy of PLL was lower when compared to the scientific literature, acting as a low quality marker for the identification of patients with CAD. In our study, there was no association between PLL and CAD. 108592 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hypertension and its Risk Factors in Male Prisoners: A Cause for Concern? DR OSUNKWO DAMARIS AMARACHUKWU1, Dan-Nwafor Chioma3, Chukwuma David Umeokonkwo3, Patrick Nguku2, Emmanuel Nna4 (1) Department of Internal Medicine, National Hospital Abuja; (2) African Field Epidemiology Network Nigeria Country Office; (3) Nigeria Field Epidemiology and Laboratory Training Program, Abuja, Nigeria; (4) Safety Molecular Pathology Lab, The Molecular Pathology Institute, Enugu Background: Hypertension is on the increase in sub-Saharan Africa and it is one of the risk factors for cardiovascular morbidity and mortality. Prisoners are at a greater risk for hypertension because of prevalent tobacco use, unhealthy diet, and incarceration-induced stress. We investigated the prevalence and the risk factors associated with hypertension among Kuje Prison inmates in the Federal Capital Territory (FCT), Nigeria. Materials & Methods: A cross-sectional study was conducted among 180 male prisoners. WHO's Stepwise approach to surveillance of chronic disease risk factors was used to conduct the study. Data collected at the various steps included: demographic and behavioral risk factors (Step 1); Blood pressure and anthropometric measurements (step 2) and Random blood sugar (Step 3). Body mass index (BMI) was determined. Data were analyzed using Epi-Info version 7. Odds of hypertension among participants with risk factors were calculated, p-value less than 0.05 was considered significant. Results: The mean systolic blood pressure was 131 +- 15 mmHg, diastolic 81 +- 12 mmHg, BMI 24.8 +- 3.6 and RBS 97.1 +- 21.8 mg/dl. Overall, 60 (33.3%) were overweight, 13 (7.2%) obese, 65 (36.1%) were prehypertensive, 57 (31.6%) were hypertensive and 1(0.6%) diabetic. The risk for elevated systolic BP was significantly higher among respondents that has first degree relative with hypertension (OR = 5.6; CI = 1.6-19.9), >=45years (OR = 7.5: CI = 1.6-35.9), insufficient physical activity (OR = 4.3; CI = 1.5-12.5; P = 0.007) and increased BMI (OR = 9.1; CI = 2.7-31.1). Conclusion: There is a high prevalence of hypertension among prison inmates in FCT, age >45 years, insufficient physical activity, family history of hypertension, and obesity were found to be independent risk factors for hypertension. 108634 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Effect of Antihypertensive Treatment on Left Ventricular Diastolic Function in Subjects with Obstructive Sleep Apnea and Hypertension: A Randomized Controlled Trial JULIANO AFONSINO JORGE1, Murilo Foppa1, Fabio Tremea Cichelero1, Deniz Martinez1, Marcelo Balbinot Lucca1, Georgia Pante3, Flavio Danni Fuchs1, Sandra Costa Fuchs1 (1) Graduate Studies Program in Cardiology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; (2) Division of Cardiology, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; (3) School of Medicine, UFRGS, Porto Alegre, RS, Brazil Obstructive sleep apnea (OSA) has been associated with left ventricular (LV) diastolic dysfunction. Treating HTN with diuretics could reduce fluid retention and rostral fluid shift in patients with OSA, leading to changes in LV diastolic parameters. We compared the effects of diuretics or amlodipine on echocardiographic LV diastolic parameters. Methods: Patients with HTN and an apnea-hypopnea index between 10 and 40 events/hour were randomized to receive chlorthalidone plus amiloride (25 mg/5 mg) daily or amlodipine (10 mg/daily) for eight weeks. The changes on echocardiographic LV diastolic function parameters were the primary outcome. Results: 62 participants completed the study. Systolic and diastolic BP (24h) decreased without between-treatment differences at the end of study. Nighttime SBP dipping was higher in the diuretic group than the amlodipine group (P = 0.01). The following deltas were found between diuretic and amlodipine groups, respectively: septal E/e' ratio, -0.20 +- 0.36 vs. 0.08 +- 0.36 (P = 0.6); lateral E/e' ratio -0.14 +- 0.22 vs. 0.66 +- 0.38 (P = 0.07); and average E/e' ratio -0.19 +- 0.21 vs. 0.43 +- 0.32 (P = 0.1). Conclusion: Patients with OSA and HTN treated with diuretics or amlodipine showed similar reductions in BP and LV structural measurements. The trend for the association of diuretics to have a greater effect on diastolic parameters and nocturnal SBP dipping suggest it can have beneficial cardiac effects in the long-term management of BP. 108659 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES The Frequency, Associated Factors and Progression of Heart Valve Disease in Chronic Kidney Disease Patients SANDRO GONCALVES DE LIMA1, Jose Arthur Viana de Oliveira Pimentel2, Manuella de Amorim Silva2, Maria Eduarda Cavalcanti Tompson2, Andrea Bezerra de Melo da Silveira Lordsleem1 (1) Hospital das Clinicas - Universidade Federal de Pernambuco - UFPE; (2) Centro Universitario Mauricio de Nassau - UNINASSAU Introduction: Cardiovascular diseases are a major cause of death in patients with advanced chronic kidney disease (CKD). Valve calcification (VC), mitral and aortic, associated with significant valve disease is a predictor of cardiovascular mortality, coronary artery disease and arrhythmias in these patients. Objectives: To assess the frequency of heart valve disease, its progression, and associated factors in patients with CKD. Methods: A total of 568 medical records of patients treated between 2007 and 2021 at the cardiology-renal outpatient clinic at a university hospital were analyzed, of which 347 were included due to the presence of CKD and heart valve disease. The explanatory variables analyzed were: age, gender, VC, glomerular filtration rate (GFR), dyslipidemia, coronary artery disease, systemic arterial hypertension, diabetes mellitus, C-reactive protein, secondary hyperparathyroidism and laboratory data on mineral and bone metabolism. To assess the association between categorical variables, the Pearson's chi-square test or Fisher's exact test was used. Results: 50.7% were female. The most frequent risk factor was systemic arterial hypertension (83.9%) and 25.1% of patients were diabetic. Mitral valve disease was observed in 81.6%, followed by aortic valve disease (66%). Regurgitant lesions were the most frequent: mitral (75%) and aortic (40.2%). Around half (48.1%) of those with heart valve disease were in the 30-39 age group, confirming the precocity of heart valve disease in CKD. A progression of heart valve disease was observed in 122 patients (35.2%). Valve calcification was significantly associated only with the progression of aortic valve disease (p = 0.01). The variables significantly associated with mitral valve disease were secondary hyperparathyroidism (p = 0.03), GFR (p = 0.02) and total cholesterol (p = 0.02). None of the variables analyzed were significantly associated with aortic and pulmonary valve disease. Secondary hyperparathyroidism (p = 0.019) was also significantly associated with tricuspid valve disease, as well as altered levels of triglycerides (p = 0.017). Conclusion: The frequency of heart valve disease, particularly mitral and aortic, is high in patients with CKD. The factors significantly associated with heart valve disease were: secondary hyperparathyroidism, GFR, total cholesterol and altered triglyceride levels. The progression of valve disease was observed in 35% of patients and was significantly influenced by VC. 108733 Modality: E-Poster Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Impact of Air Quality During Sleep on Cardiorespiratory Dynamics: An Exploratory Study MIGUEL MEIRA E CRUZ1, Joana Belo2, Mariana Picado3, Nuno Canha5, Carla Viegas2, Susana Marta Almeida4 (1) Centro Europeu do Sono; Sleep Unit, Centro Cardiovascular da Universidade de Lisboa, Lisbon, Portugal; (2) H& & Technology Research Center, Superior de Tecnologia da Saude, Instituto Politecnico de, Lisboa, Portugal; (3) Instituto Portugues de Oncologia de Lisboa, Lisbon, Portugal; (4) Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Tecnico, Universidade de Lisboa, Lisbon, Portugal; (5) Centre for Environmental and Marine Studies, Department of Environment and Planning, University of Aveiro, Aveiro, Portugal; (6) NOVA National School of Public Health, Public Health Research Centre, Universidade NOVA de, Lisboa, Portugal; (7) Comprehensive Health Research Center (CHRC), Portugal Introduction: Inadequate sleep and poor air quality are both associated to an increased cardiovascular risk. Sleep quality and structure are also vulnerable to environmental influences. Typically, sleeping environments have low ventilation rates, leading to pollutants accumulation. Though during nighttime and early morning there is a circadian propensity to cardiorespiratory events, environmental factors which may aggravate this risk should be taken into account. The aim of this study is to test the associations between ais pollutants, specifically CO and CO2 and heart rate dynamics as an indicator of cardiovascular autonomic function. Methodology: Ten men followed specific inclusion criteria: age between 25 and 40 years old, healthy individuals, non-smoking, without children below five years and without sleeping, cardiac and respiratory problems and whose households are within Lisbon area, were recruited. An unattended polysomnography (PSG) was performed during 2 weeknights in a row. The second night PSG's results were used in order to minimize the first night effect. For the propose of this study the data related to heart rate (HR) were collected, namely HR acceleration index (HR Acc index), mean of HR (HRmean) and minimum of HR (HRmin). IAQ monitoring was based on a comprehensive multi-pollutant assessment where chemical, in particular carbon dioxide (CO) and carbon monoxide (CO), were assessed through real time instruments. Non-parametric statistics were applied, namely Spearman correlations, to analyze potential associations between sleep and environmental parameters. The level of significance considered was a = 0.05. Results: The mean age was 33.9 +- 5.20 years. HR and IAQ parameters showed a moderately positive correlation between CO exposure and HR Acc index (rs = .635) and HRmin (rs = .0,667) and a highly positive correlated between CO exposure and HRmean (rs = .0,71); also a moderately and positive correlation between CO2 exposure and HR Acc index (rs = .668) awas observed as well as a highly positive correlation between CO2 exposure and HRmin (rs = 713) HRmean (rs = .0,794). Conclusions: Results from this preliminar study suggest that high levels of CO and CO2 may increase the HR Acc index, HRmin and HRmean, raising awareness on the possible impact of indoor air quality on cardiovascular autonomic modulation. Further studies are needed to confirm such findings and to establish their clinical relevance within cardiorespiratory health. 108720 Modality: E-Poster Researcher - Non-case Report Category: ANTICOAGULATION The Relationship between Baseline Characteristics and Ischemic Stroke in Patients with Atrial Fibrillation After Transcatheter Aortic Valve Replacement Treated with Edoxaban or Vitamin K Antagonists CHRISTIAN HENGSTENBERG1, Martin Unverdorben2, Helge Mollmann3, Nicolas M Van Mieghem4, Holger Thiele5, Peter Nordbeck6, Tienush Rassaf7, Raul Moreno8, Roxana Mehran9, Irene Lang1, Roland Veltkamp10, George D Dangas9 (1) Department of Internal Medicine II, Division of Cardiology, Vienna General Hospital, Medical University, Vienna, Austria; (2) Daiichi Sankyo, Inc., Basking Ridge, NJ, USA; (3) Department of Internal Medicine, St. Johannes Hospital, Dortmund, Germany; (4) Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, the Netherlands; (5) Department of Internal Medicine-Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig; (6) Department of Internal Medicine I, University Hospital Wurzburg, Wurzburg & Klinikum Links der Weser gGmbH, Bremen, Germany; (7) Clinic for Cardiology and Vascular Medicine, Essen University Hospital, Essen, Germany; (8) Department of Cardiology, Tubingen University Hospital, Tubingen, Germany; (9) Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York, NY, USA; (10) Division of Brain Sciences, Imperial College London, London, UK; Department of Neurology, Alfried Krupp Krankenhaus, Essen, Germany Introduction: In ENVISAGE-TAVI AF (NCT02943785) edoxaban was noninferior to vitamin K antagonists (VKAs) for the composite endpoint of net adverse clinical events in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR). Objective: To evaluate the association between baseline patient characteristics and ischemic stroke (IS) incidence. Methods: This on-treatment analysis of ENVISAGE-TAVI AF included patients that received >=1 dose of the study drug over the period treatment and <=3 days after interruption or discontinuation. Baseline demographic and clinical characteristics were stratified by IS incidence. Numerical variables were compared using one-way analysis of variance; categorical variables were compared using Fisher's exact test. Stepwise logistic regression with 30 independent predictors determined patient characteristics associated with first IS event. Results: Of 1377 patients included in the on-treatment analysis, 41 (3.0%) experienced IS during the on-treatment period (edoxaban, n = 19; VKA, n = 22). Most IS events occurred within 6 months of TAVR for both the edoxaban (57.9%) and VKA (68.2%) arms. Differences in baseline demographic and clinical characteristics are shown for patients who did or did not experience IS while receiving treatment (Table). Significantly more patients who experienced IS had a history of systemic embolic events (SEE; P = 0.015). Only a history of SEE was independently associated with IS (P = 0.006). Body mass index (P = 0.052) and history of myocardial infarction (P = 0.074) were numerically, but not statistically, associated with IS. Conclusions: In this on-treatment analysis of the ENVISAGE-TAVI AF trial, few patients experienced IS. Patients with history of SEE may be at increased risk of IS following TAVR. 109072 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Impact of Hospital Acquisition of COVID-19 on Cardiac Patients CRISTIANE DA CRUZ LAMAS1, Mariah Rodrigues Paulino1, Leo Rodrigo Abrahao dos Santos2, Ingrid Paiva Duarte2, Marcelo Goulart Correia1, Jose Alfredo de Sousa Moreira1, Leticia Roberto Sabioni1, Fabiana Bergamin Mucillo1, Rafael Quaresma Garrido1, Bruno Zappa1, Stephan Lachtermacher Pacheco1, Andrea Rocha de Lorenzo1 (1) Instituto Nacional de Cardiologia; (2) Universidade do Grande Rio Introduction: Reported nosocomial acquisition of COVID-19 has varied between 5 to 41%. Our aim was to describe the demographic, clinical and laboratory features and outcomes of patients with cardiac disease hospitalized with COVID-19 in a reference cardiology institution in Brazil, comparing the patients with hospital-acquired COVID-19 (HACOVID19) with those who had non-hospital acquired (NHA) COVID-19. Methods: This is an observational retrospective study of consecutive adult patients admitted, between March and September of 2020 with a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR. Data was collected as per the International Severe Acute Respiratory and Emerging Infection Consortium and complemented with a cardiovascular questionnaire. HA COVID-19 was considered when the patient had a negative nasopharyngeal swab on admission and a positive one 14 or more days later. Statistical analysis was performed using the Jamovi 1.6 and R 4.0.1. Results: One hundred twenty-one patients with a confirmed diagnosis of COVID-19 were included. There were 20 patients (16.5%) with HA-COVID19 and 101 (83.5%) with NHA-COVID-19. Patients who developed COVID-19 in hospital had as reasons for admission: decompensated heart failure (35%), acute coronary syndrome (20%), cardiac surgery (CABG, valve replacement or aortic surgery) in 25%, complete AV block, pacemaker dysfunction, stroke and hematologic disease (5% each). The median(IQR) length of stay of HACOVID19 was 29 days (18.5-60.2) vs 16 (7-31)days. Median age was 64 years (61.8-69.3) for HA-COVID-19, and 63 (52-72) for NHACOVID19. There was no difference between patients with HACOVID-19 and those with NHACOVID-19 regarding the presence of heart disease, COPD, obesity, complicated diabetes mellitus, heart valve disease, coronary artery disease, and systemic arterial hypertension. However the 2 groups were significantly different regarding laboratory features (serum creatinine, D-dimer, ferritin, AST). HACOVID patients had more dyslipidemia (15/20 (75%) vs 49/101 (48.5%), P = 0.030] and chronic renal failure [7/20 (35%) vs 15/101 (15%), p = 0.033]. Most importantly, mortality was significantly higher in HACOVID-19[10/20 (50%) vs 19/101 (18.8%), p = 0.003]. Conclusions: Cardiac patients who acquired COVID-19 in hospital had longer hospital stay and higher mortality, which highlights the impact of the pandemic on the outcomes of cardiac patients admitted to hospital for cardiac, non-COVID related reasons. 108800 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Evaluating the Value of Point-of-Care NT-proBNP for the Screening of Pregnancy-Related Heart Failure - the Preg-HF Study CHARLE ANDRE VILJOEN1, Mahmoud Al-Naili2, Jean Jacques Noubiap3, Alice Jackson4, Karice Hyun5, Andrea Neves6, Clovis Nkoke7, Charles Mondo8, Juliet Nabbaale9, Julian Hoevelmann10 (1) Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; (2) Division of Cardiology, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; (3) Centre for Heart Rhythm Disorders, The University of Adelaide, Adelaide, Australia; (4) British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, Scotland; (5) School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Westmead 2145, Australia; (6) Gynecology and Obstetrics, Hospital Geral Jose Macamo, Av. OUA, 1100, Maputo, Mozambique; (7) Department of Internal Medicine, Buea Regional Hospital, Buea, Cameroon; (8) St. Francis Hospital Nsambya, P. O. Box 1799, Nsambya Road, Kampala, Uganda; (9) Uganda Heart Institute, Plot No. 1, Upper Mulago Hill, P. O. Box 37392, Kampala, Uganda; (10) Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Saarland University Hospital, Homburg (Saar), Deutschland Introduction: Cardiac disease is an important cause of maternal mortality worldwide. However, diagnosing heart failure (HF) during pregnancy remains challenging. Patients with HF present with symptoms that are often attributed to the physiological changes of pregnancy. Although the measurement of natriuretic peptides has been recommended as a cost-effective screening test for HF, its value in predicting underlying structural heart disease on echocardiography during pregnancy is unclear. We aimed to evaluate the accuracy of point-of-care (POC) NT-proBNP to predict echocardiographic evidence of structural heart disease in pregnant women. Methods All consecutive consenting pregnant women with symptoms of HF, who underwent echocardiography at a tertiary hospital in Cape Town, South Africa, between March 2021 and March 2022 were compared with asymptomatic pregnant women. Demographic and obstetric data were collected, as well as clinical and echocardiographic parameters. POC NT-proBNP was measured; a receiver operating characteristic (ROC) curve was used to determine the level of NT-proBNP that would have the best predictive value for detecting structural heart disease on echocardiography. Results: We included 121 women with a median age of 31.3 years (IQR 24.9-36.4), gravidity of 3 (2-4), mostly in their third trimester of pregnancy (76.9%). Symptomatic women (66.9%) presented mainly with dyspnoea (90.8%) and peripheral oedema (50%). Overall, the median POC NT-proBNP was 108 pg/ml (60-470) but was not statistically different between symptomatic and asymptomatic participants. However, NT-proBNP levels were significantly elevated in those with left ventricular (LV) dilatation (395 [86-1668] vs 80.5 [60-303], p = 0.001), left atrial enlargement (417 [98-1211] vs 78 [59-167], p < 0.001), LV systolic dysfunction (539 [94-2582] vs 80 [60-323], p < 0.001), diastolic dysfunction (300 [77-1450] vs 80 [60-322], p = 0.038), mitral regurgitation (247 [60-794] vs 84 [60-323], p = 0.027) and pericardial effusion (448 [84-1487] vs 80 [60-303], p < 0.001). An NT-proBNP of <250 pg/ml had the highest negative predictive value (79.3%) to rule out structural heart disease (ROC area 0.66). Conclusion: In this cohort of pregnant women with symptoms HF, POC NT-proBNP identified those with structural heart disease with acceptable discrimination. POC NT-proBNP testing might be particularly useful as a screening test in settings where pregnant women do not readily have access to echocardiography. 108804 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Health Coaching for Patients in Cardiac Rehabilitation: Results of a Program to Promote Healthy Lifestyle Habits DANIELE BARRIONUEVO KALLAS1, Lia Kanae Okita Buschinelli1, Eneas Antonio Rocco1, Amanda Barbuio Teixeira1, Luana Talita Diniz Ferreira1, Raquel Yuri Mori1, Bianca Sprovieri Moraes1, Gabriela Macoppi Carreiro1, Gabriela Zanussi Barreto1, Camila dos Santos Arcas1, Felipe Lopes Malafaia1, Patricia Canteruccio Pontes Vianna1 (1) Hospital Samaritano Paulista Introduction: Health Coaching (HC) is an approach for changes in health behaviors and self-care. The British Association for Cardiovascular Prevention lists health behavior change, education, and management of risk factors related to physical activity, diet, weight control, alcohol and tobacco among the 6 central components of cardiac rehabilitation (CR) programs. Thus, interventions based on changes in health behaviors are justified as part of medical care. Objective: To evaluate the impact of a HC Program in lifestyle of patients under CR immediately after and 6 months after the intervention. Methods: Patients in CR of a specialized institution were invited to voluntarily enroll in a HC Program in the dimensions of diet, physical activity, stress management and sleep. The intervention was composed of 6 weekly coaching sessions, with trained health professionals, lasting 1h30, made 100% remote by the telemedicine of the institution, where patients were gathered in groups of up to 4 people, plus the Health Coach. Fantastic Lifestyle Questionnaire (Fantastic) was applied before, immediately after and 6 months after the intervention. Sessions addressed wellness, ambivalence, behavioral change process, thoughts and beliefs, relapse prevention and habit support plan, and patients were invited to create health goals with the Smart framework to a day-to-day practice. Between sessions they received educational materials about the four dimensions. Results: The intervention took place between August 2020 and March 2022. 31 patients completed the program. Results of the Fantastic are at Table 1. Conclusions: Interventions for health behavior changes seem to be promising for patients in CR and seem to last after 6 months. 108810 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM NKG2A Expression Among CD8 Cells is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the Brace Corona Randomized Trial RENATA JUNQUEIRA MOLL BERNARDES1, Sergio Costa Fortier3, Andrea Silvestre de Sousa4, Renato D. Lopes6, Andre Feldman8, Guilherme D.A.S. Arruda9, Denilson C. de Albuquerque1, Ariane V. S. Macedo7, Olga Ferreira de Souza1, Fernando A. Bozza1, Ronir Raggio Luiz5, Emiliano Medei2 (1) D'Or Institute for Research and Education, Rio de Janeiro, Brazil; (2) National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Brazil; (3) Patological Anatomy Laboratory, Rede D'Or Sao Luiz, Sao Paulo, Brazil; (4) Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; (5) Public Health Studies Institute - IESC, Federal University of Rio de Janeiro, Brazil; (6) Brazilian Clinical Research Institute, Sao Paulo, Brazil; (7) Hospital Sao Luiz Jabaquara, Sao Paulo, Brazil; (8) Hospital Sao Luiz Analia Franco, Sao Paulo, Brazil; (9) Hospital Sao Luiz Sao Caetano, Sao Caetano do Sul, Brazil; (10) Hospital Sino Brasileiro, Osasco, Brazil; (11) Hospital Villa Lobos, Sao Paulo, Brazil; (12) Hospital Sao Luiz Morumbi, Sao Paulo, Brazil Background: Cardiovascular comorbidities and immune response dysregulation are associated with 2019 coronavirus disease (COVID-19) severity. Reduced populations of lymphocytes, including T, B, and natural killer cells, and increased neutrophil counts have been detected in patients with COVID-19. We aimed to explore the key immune cell profile and understand its association with disease progression in patients with hypertension hospitalized due to COVID-19. Methods: Immune cell populations in cryopreserved peripheral blood mononuclear cell samples were obtained from 156 hypertensive patients who were included in the BRACE CORONA randomized trial. The primary outcome was progression to severe disease, according to a modified World Health Organization Ordinal Scale for Clinical Improvement, during hospitalization. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Results: During hospitalization, 11 (7.1%) patients showed progression to more severe COVID-19; 3 of these patients died. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography (CT) examination, the C-reactive protein concentration, total lymphocyte count, proportions of CD4+ and CD8+ T cells, CD4/CD8 ratio, CD8+ human leukocyte antigen DR isotope (HLA-DR) median fluorescent intensity (MFI), and CD8+ natural killer group 2 member A (NKG2A) MFI on admission were associated with progression to severe COVID-19. According to our predictive model, the risk of progression to severe disease reached 86.2% in the presence of three clinical variables (obesity, diabetes, reduced oxygen saturation, or >50% CT lung involvement) combined with increased CD8+ NKG2A MFI. Conclusions: This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications. 109063 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Improvement of Heart Rate Variability as a Surrogate Measure of Cardiovascular Autonomic Function in Comisa Patients Treated with a Mandibular Advancement Device MIGUEL MEIRA E CRUZ1, Luis Vicente Franco de Oliveira3, Monica Gomes2, Lilian Giannasi2 (1) Centro Europeu do Sono; Sleep Unit, Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal; (2) Universidade Estadual de Sao Paulo - UNESP, Sao Jose dos Campos, Sao Paulo, Brazil; (3) Centro Universitario de Anapolis-UniEvangelica, Sao Paulo, Brazil Introduction: COMISA refers to the frequent co-occurrence of Insomnia and Sleep Apnea and has been linked to increased cardiovascular risk where autonomic dysfunction play an important role. Therefore, improving cardiovascular autonomic function (CAF) is a clinically relevant target to be achieved in these patients. While mandibular advancement devices (MAD) are recommended as an effective alternative for obstructive sleep apnea control, the benefits of such therapeutic tool in COMISA remains elusive. In this pilot study we aimed to test the null hypothesis that MAD will have no effect on heart rate variability (HRV) as a surrogate of CAF in COMISA adult patients. Methodology: Patients with COMISA, as defined by OSA + Sleep Latency >30min, were treated with PMPositioner oral appliance (OAm) for their sleep disordered breathing and were evaluated after 3 months of OAm therapy, been retrospectively compared regarding major clinical and polysomnographic outcomes. Sleep variables were evaluated by PSG and Heart rate variability (HRV) was accessed and analized by rythmography. Results: 12 COMISA patients (6 males), mean age = 49.7, mean BMI = 25.9, mean neck circumference = 38.9 were enrolled. Insomnia and OSA were confirmed by both clinical criteria (validated questionnaires) and PSG parameters. All patients were treated with a PMPositioner oral appliance for sleep disorder breathing. The AHI was reduced from 22.7 +- 12.7 to 4.0 +- 3.5(p < 0.0002), IDO was reduced from 18.8 +- 14.0 to 3,5 +- 2.0 (p < 0.02), sleep latency reduced from 63.1 +- 49.4 to 21.8 +- 21.4 (p < 0.2), reaching a normal level. The time-domain and frequency-domain parameters were significant for RR interval and both Fast Fourrier Transform and Wavelet spectral method, respectively. Conclusions: The rejection of the null hypothesis allow us to confirm the impact of MAD in HRV of these patients. This is the first study showing a positive and clinically relevant effect of MAD therapy on both respiratory and insomnia related therapeutic outcomes in COMISA together with an improvement of CAF and therefore on cardiovascular risk as a major concern among these patients. 109361 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Pulse-Wave Velocity in Down Syndrome Individuals ANNE GERYMAIA OLIVEIRA DE MELO SILVA1, ANNE GERYMAIA OLIVEIRA DE MELO SILVA1, NEILA ANDERS AIDAR2 (1) SECRETARIA DE SAUDE DO DISTRITO FEDERAL; (2) MEDCOR Introduction: The interest in understanding what accelerates the degradation of cardiovascular function in some individuals, is matched by the need to understand what protects other subjects. Pulse-wave velocity (PWV) is a measurement of arterial stiffness that is an independent predictor of cardiovascular risk. It can be measured simply and noninvasively by modern oscillometric methods. Objectives: To evaluate vascular aging variables and arterial stiffness in adult patients with trisomy 21, treated at the Distrito Federal Down Syndrome Reference Center - Crisdown. Methods: Transversal study of PWV in 28 adults with Down syndrome. The central hemodynamic parameters of blood pressure, pulse wave velocity (PWV), and heart rate-adjusted increase index (Alx@75) were estimated using the oscillometric device Arteris-AOP (Cardio Sistemas Comercial e Industrial Ltda, Sao Paulo, Brazil), ANVISA 10361059013. The device performs the analysis through a cuff installed on the patients' left arm. The software was used for data analysis comparing with a database with the Brazilian population matched by sex, age, weight, and height. Results: Twenty-eight patients with Down Syndrome ranging from 18 to 64 years old, being 18 female and 10 male, were evaluated. For data analysis, they were divided into groups of 18 to 24 years (N = 13), 25 to 34 years (N = 6), and over 35 years (N = 9). There was no statistical difference between the groups regarding mean BMI (30.7 + 4.3 Kg/m2), mean central systolic pressure - CSP (85.6 + 10.5 mmHg), mean central diastolic pressure - CDP (62.3 + 10.1 mmHg), mean cardiac output (3.4 + 0.5 l/min) and mean total cholesterol serum level (171.7 + 35.3 mg/dl). The mean PWV was 5.2 m/s (SD 1.4) and the mean augmentation index was 17.5% (SD 8.5). There was a statistical difference between the groups in relation to pulse wave velocity and augmentation index, which were significantly higher in the group aged over 35 years. Compared with a database of the typical Brazilian population, the level of PWV in adults with Down Syndrome was within the average, even in the group aged over 35 years. Conclusion: The findings suggest that adults with Down syndrome have a pattern of central arterial hypotension. The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants, including arterial pressure suggests Down syndrome-specific phenomena may alter such relationships in this population. 109071 Modality: E-Poster Researcher - Non-case Report Category: NURSING Instrument to Guide Nurses in the Physical Examination of Patients with Suspected Low Cardiac Output MIRIAN FIORESI1, Juliana Mitre da Silva1, Candida Canicali Primo1, Maria Edla de Oliveira Bringuente1, Bruno Henrique Fiorin1, Karolini Zuqui Nunes1, Lorena Barros Furieri1, Walckiria Garcia Romero Sipolatti1 (1) Programa de Pos-Graduacao em Enfermagem, Universidade Federal do Espirito Santo Introduction: The concept of decreased cardiac output is found mainly in the nursing and medical fields. As a nursing phenomenon, it is present in the NANDA-I and ICNP classification systems. Nurses are the professionals who stay the longest in direct care of people, so they commonly identify clinical changes and signs of deterioration of patients' health at all levels of health care. Therefore, a data collection instrument can optimize risk prediction in adults and facilitate clinical thinking and nursing care for patients with this condition. Objective: To develop an instrument to assist nursing in the physical examinations of a suspected low cardiac output patients. Methods: This is a methodological study developed in three stages: literature scope review, pilot instrument construction and validation by judges. The instrument was constructed following the principles of Pasquali's elaboration of instrument. Content and face validation was based on content validity index (CVI) and was considered as inclusion criteria CVI greater than or equal to 0.8. The judging population consisted of nurses with a minimum degree of specialist and minimum experience of two years in the field of nursing cardiology. The items that made up the instrument were evaluated as: , adequacy and , within the criteria of clarity, relevance or representativeness and comprehensiveness. Results: After the validation process, the instrument was composed of the following nine items, called clinical indicators: consciousness status, respiratory status, activity tolerance, fluid volume, gastric status, sensory alteration of cardiac origin, heart rate and rhythm, blood pressure and tissue perfusion. Each item can be scored from 1 to 3 in ascending order of severity and by summing the total points the patient risk can be stratified into: minimum risk (9 to 12 points), intermediate risk (13 to 18 points) and high risk (19 to 27 points). If the patient is tired with minor exertion (eating) and/or presents with chest pain that does not cease at rest and therapy, he/she should be classified as high risk even if the patient has a score below 19 points. Conclusion: An instrument to assist nursing in the assessment was developed and validated to classify the risk of decreased cardiac output in adults that can support nursing care and favor the clinical reasoning of nurses in the nursing process to patients who present signs and symptoms of this phenomenon. 108869 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Correlation between Myocardial Strain, Mechanical Dyssynchrony, and the Presence of Myocardial Fibrosis in the Mild Cardiac Form of Chagas Disease POLYANA EVANGELISTA LIMA1, Andre Mauricio Souza Fernandes2, Marta Silva Menezes1, Edmundo Jose NassriCamara2, Rafael de Castro da Silva2, Heverton Garcia de Oliveira3, Sarah Rodrigues de Assuncao Vaz3, Alane Mota dos Santos3, Matheus Pereira Barreira3 (1) Escola Bahiana de Medicina e Saude Publica; (2) Universidade Federal da Bahia; (3) Universidade Federal do Vale do Sao Francisco Introduction: Early identification of myocardial damage appears to be important in the approach to patients with Chagas disease (CD). Echocardiography with strain obtained by speckle tracking (STE) and the evaluation of myocardial fibrosis (MF) through cardiac magnetic resonance imaging (CMRI) may be promising diagnostic methods in this regard. Objective: Evaluate myocardial involvement, specifically in the chronic mild cardiac form of CD using strain by STE and MF by CMRI, as well as their correlations. Methods: A cross-sectional study analyzed patients with the chronic mild cardiac form of CD (preserved ejection fraction) who underwent STE strain echocardiography and CMRI. Results: Twenty-one participants were included (female: 62%, age: 54 +/- 5 years). The prevalence of MF by late myocardial enhancement (LME) was 50%. Global longitudinal strain (GLS) was decreased in 17 patients (81%) with a median of 14.1% (interquartile range 12.1-16.3). The average T1 mapping values were high in patients with CD (993 +/- 163 ms). T1 mapping was significantly correlated with GLS (r = 0.634; p = 0.015). Furthermore, the mechanical dispersion index obtained by strain was increased (>55 ms) by 84%, with the largest area under the receiver operating characteristic curve (AUC 0.696; 95% confidence interval 0.412-0.981) for fibrosis discrimination by LME. Conclusion: The present study suggests that myocardial strain and T1 mapping behave as early markers of myocardial damage in mild chronic CD. The mechanical dispersion index was elevated, and it was the parameter that most correlated with myocardial fibrosis by LME. 108876 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Screening of Cardiovascular Problems in 129 Adults with Down Syndrome ANNE GERYMAIA OLIVEIRA DE MELO SILVA1, NEILA ANDERS AIDAR2, MARIA CAROLINA VIANA VALE1 (1) SECRETARIA DE SAUDE DO DISTRITO FEDERAL; (2) MEDCOR Introduction: Down syndrome continues to be the most common chromosomal condition, with rising prevalence and increased survival. With increased longevity, such individuals are susceptible to differing cardiovascular disorders. Objectives: Describe cardiovascular disorders in adults with Down Syndrome. Methods: Descritive and observational study of 129 adults with cytogenetically and/or clinically proven Down syndrome. For each individual, carers were interviewed to elicit a past history of any medical condition and to elicit any symptoms suggestive of an ongoing medical illness. A standard physical examination was undertaken. Results: 129 adults with Down syndrome participated in this study, sex distribution being 65 (50.3%) males and 64 females. The mean age of the sample population was 29 years; range 18-64 years. The individuals were living in their family homes. The commonest cardiac disorders were cardiac congenital malformation in 43 (33.3%), dyslipidemia in 37 (28.7%) subjects, cardiac arrhythmia in 12 (9.3%) and dysautonomic disorders in 10 (7.7%). The commonest cardiac malformations were valvular diseases in 21 (16.3%) atrioventricular septal defect in 13 (10.0%), interatrial septal defect in 11 (8.5%), interventricular septal defect in 9 (7.0%), patent ductus arteriosus in 9 (7.0%). The mean rate was 74 beats per minute (SD 14), the mean systolic arterial pressure was 118.7 mmHg (SD 21.6), the mean diastolic arterial pressure was 77.2 mmHg (SD 16.2) and the mean oxygen saturation level was 95% (SD 4). The mean body mass index was 30.8 kg/m2 (SD 15.4), overweight and obesity was observed in 67.6% of individuals. The mean cholesterol was 175.1 mg/dl (SD 46.6). Other important clinical disorders was hypothyroidism in 52 (40.3%) individuals, epilepsy in 17 (13.1%) and diabetes mellitus in 6 (4.6%). Screening of obstructive sleep apnea (OSA) was positive in 20 cases (15.5%), being 13 (10.0%) considered severe OSA and 7 (5.4%) moderate OSA. Carotid ultrasound was performed on 26 individuals and measurement of intima-media thickness was normal in all cases. Conclusion: Overweight/obesity, dyslipidemia and cardiac defects were frequently. Considering that Down syndrome presents with chronic hypotension, it is reasonable to propose that the prolonged reduction of arterial distending pressure may contribute to functional preservation of the arteries in patients with Down syndrome. 108881 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Native T1 Mapping and Myocardial Fibrosis in the Mild Cardiac Form of Chagas Disease POLYANA EVANGELISTA LIMA1, Rafael de Castro da Silva -Silva1, Andre Mauricio Souza Fernandes2, Marta Silva Menezes1, Edmundo Jose NassriCamara2, Matheus Pereira Barreira3, Alane Mota dos Santos3, Sarah Rodrigues de Assuncao Vaz3, Heverton Garcia de Oliveira3 (1) Escola Bahiana de Medicina e Saude Publica; (2) Universidade Federal da Bahia; (3) Universidade Federal do Vale do Sao Francisco Introduction: Chronic Chagas cardiomyopathy presents as chronic myocardial inflammation that causes progressive tissue destruction and extensive fibrosis. Cardiac magnetic resonance (CMR) is the gold standard noninvasive test to assess myocardial fibrosis (MF) using the technique of late myocardial enhancement (LME). CMR has recently been used to perform new evaluations with parametric mapping (T1 and T2). It is possible that the use of the T1 mapping technique generates complementary and even prognostic information in the evolution of patients with CD. Objective: Describe the T1 mapping values obtained with CMR in the evaluation of patients with CD and their correlation with the LME technique. Methods: This cross-sectional study analyzed patients with the chronic mild cardiac form of CD who underwent CMR. Eligible patients underwent CMR to analyze MF by 2 techniques: the LME technique, which was categorized as present/absent for MF, and T1 mapping time, expressed as average +/- standard deviation. Discussion: Sixteen patients composed the study population; 81% female, and the mean age was 54.3 +/- 5.3 years. Mean left ventricular ejection fraction was 65.3% +/- 5.4%. The prevalence of MF in the sample using the LME technique by CMR was 50%. The T1 mapping values were high in patients with CD without ventricular dysfunction, with mean of 993 +/- 163 ms. The medians and interquartile range (IQR) of T1 mapping were: 1033 (IQR 998-1081) in group I and 1010 (IQR 1002-1047) in group II. In the MF group, the times were even higher, as found in other dilated cardiomyopathies. Conclusion: These data reinforce the ability of T1 mapping to identify MF more completely and earlier when compared with LME and suggest that this technique is a marker of early cardiac involvement by CD. 108908 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Crossover in the Elderly in Brazil: Time Trend Analysis of Heart Failure Mortality from 1996 to 2019 EDUARDO PITTHAN1, Vania Hirakata2, Natanael Alves de Lima1, Thiago Emanuel Rodrigues Novaes1, Pamela Sandri1 (1) Universidade Federal da Fronteira Sul Passo Fundo; (2) Instituto de Cardiologia do Rio Grande do Sul Introduction: In Brazil, the clinical-epidemiological scenario of Heart Failure (HF) has shown significant changes in recent decades. The main factors that have affected the change in profile were the exponential increase in the elderly population and the impact of new therapies. Objective: To evaluate the trend of variation in gross mortality rates in HF in Brazil from 1996 to 2019, comparing with the variation in the growth of the elderly population stratified by age groups. Methods: Refers to an ecological, descriptive and quantitative study that used data available on DATASUS on March 8th 2022 regarding to mortality in the elderly due to HF, in Brazil, from 1996 to 2019, divided into three age groups: 60 to 69 years, 70 to 79 years and 80 years or more. The gross mortality rates in these variables were calculated per 100,000 inhabitants, based on the population variation in Brazil in the years chosen for the study, made available by IBGE in a consultation that happened on March 8th 2022. Results: The analysis of mortality from HF over 80 years, in 1996, shows a rate of 770.2/105 inhabitants and showed a significant drop in 2019, being 324.4/105 inhabitants. Making a drop of 57.9% per 105 inhabitants. On the other hand, in the same period, the population of this age group has increased 172.5%. The analysis of mortality from HF from 60 to 69 years, in 1996, showed a rate of 87.6/105 inhabitants and showed a significant drop in 2019, being 26.6/105 inhabitants. Making a drop of 69.6% per 105 inhabitants. On the other hand, in the same period, the population of this age group has increased 120.7%. In the 70-79 age group, in 1996, it had a mortality rate of 248.1/105 inhabitants and showed a significant drop in 2019, being 79.6/105 inhabitants. Making a drop of 67.9% per 105 inhabitants. On the other hand, in the same period, the population of this age group has increased 121.3%. Conclusion: The results of this study demonstrate downward trends in the mortality rate from HF in the elderly in Brazil in recent decades. In contrast, there has been an exponential increase in the elderly population in all ages studied. 108942 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Does Long-Term Storage in 4% Formaldehyde Changes the Expression of Immunophenotypic Markers of Glutaraldehyde-Treated Bovine Pericardium? LUIZ FERNANDO KUBRUSLY1, Douglas Mesadri Gewehr2, Alexandre Gelas Haddad1, Victor Daniel Falkenbach Tenius1, Fernanda Prehs Izar1, Allan Fernando Giovanini1, Fernando Bermudez Kubrusly3 (1) Mackenzie Evangelical School of Parana, Curitiba, Parana, Brazil; (2) Denton Cooley Institute of Research, Science and Technology, Curitiba, Parana, Brazil; (3) Curitiba Heart Institute, Curitiba, Parana, Brazil Introduction: The bovine pericardium is a biological tissue widely used as a biomaterial for tissue engineering applications. Glutaraldehyde and formaldehyde are frequently used in these reticulation processes to improve the material's resistance and preservation. Objective: The objective was to evaluate the impact of long-term storage in 4% formaldehyde on the quantitative expression of immunophenotypic markers of glutaraldehyde-treated bovine pericardium. Methods: Bovine pericardium (BP) patches used were produced and supplied by Braile Biomedica(r). We performed a histological and immunohistochemical analysis comparing two patches of BP, one manufactured in 2009, thickening 0.35 mm/measuring 35 cm2, and another manufactured in 2020, thickening 0.36 mm/measuring 99 cm2. BP were fixed in a 10% formalin solution for 24h, embedded in paraffin blocks, trimmed and mounted on histological glasses. Sections were stained with H&E, Weigert and picrosirius red and immunolabeled with vimentin, laminin 5, collagen I and collagen IV using a standardized protocol. Images were captured using light and polarized microscopy and the area of antibody signal was quantified using Image J Software. Results: Histological analysis of the patches showed no autolysis or significant changes. In immunohistochemical analysis, collagen I and IV was diffused throughout the connective tissue of the patches. In 2020 specimen, collagen I occupied an area of 21.36% and collagen IV an area of 24.67%, while in the 2009 specimen, only 15.87% (collagen I) and 12.02% (collagen IV). Laminin was not reacted between the specimens. Immunopositivity for vimentin differed markedly between patches occupying a 54% area in the 2020 patch and a 13% area in the 2009 patch. Conclusion: We observed no expressive differences in immunophenotypic expression between 2009 and 2020 bovine pericardia, except for the higher expression of the vimentin in the 2020 bovine pericardium patch. 108955 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Epidemiological Transition in the Elderly in Brazil: Time Trend Analysis of Heart Failure Mortality by Gender from 1996 to 2019 EDUARDO PITTHAN1, Vania Hirakata2, Pamela Sandri1, Guilherme Sommavilla1 (1) Universidade Federal da Fronteira Sul Passo Fundo; (2) Instituto de Cardiologia do Rio Grande do Sul Introduction: Heart failure (HF) presents epidemic characteristics with considerable impact on morbidity and mortality, especially among the elderly. In Brazil, HF is responsible for high mortality rates. Objectives: To evaluate the variation trend of HF gross mortality rates by gender in the elderly in Brazil, comparing with the variability of population growth by age group and gross mortality rate from all causes in recent decades. Methods: An ecological study that used data available on DATASUS on March 2022, regarding mortality by gender in elderly people with HF in Brazil, from 1996 to 2019, stratified into three age groups: 60 to 69 years, 70 to 79 years and >80 years. The gross mortality rates were calculated in these variables per 105 inhabitants, comparing with the variation of the population in Brazil in the years that were studied, made available by the IBGE in a consultation on March 2022. Results: In the analysis of HF mortality in Brazil in men aged 60 to 69 years, there has been a decrease of 67%, falling from 98/105 inhabitants to 32/105 inhabitants. In the same age group, among women, the gross death rate has decreased 72%, falling from 77/105 to 21/105 inhabitants. In contrast, the male and female population aged 60 to 69 has grown 119% and 121%, respectively. In men aged 70 to 79 years, the mortality rate has dropped from 269/105 to 94/105 inhabitants, with a drop of 65%. Moreover, among women in this age group, there has been a drop of 70%, from 229/105 to 68/105 inhabitants. In contrast, the male population grew 112% and the female population 129%. In the age group of more than 80 years, in the same period, male mortality has decreased 54%, falling from 741/105 inhabitants to 339/105 inhabitants. In women, there was a drop of 60%, falling from 785/105 inhabitants to 315/105 inhabitants. In contrast, the male population has grown 151% and the female population, 187%. Conclusion: This study demonstrates trends of a significant decrease in the mortality rate from HF in elderly people of both genders in Brazil in the recent decades. This trend is more pronounced in women aged 60 to 79 years. 108973 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Evaluation of Health Literacy in Patients with Systemic Arterial Hypertension in Northeastern Brazil ROMERO HENRIQUE DE ALMEIDA BARBOSA1, Luana Resende Cangussu1, Eduardo Antonio Sartori Alho1, Matheus Rodrigues Lopes1 (1) Universidade Federal do Vale do Sao Francisco Introduction: Health literacy comprises the cognitive and social skills that determine an individual's ability to obtain, process, understand and use health and medical information to make decisions that are relevant to their own health. Cardiovascular diseases are the leading causes of death in Brazil and Systemic Arterial Hypertension (SAH) contributes directly or indirectly to 50% of these deaths. Poor health literacy can impact in the management and control of these comorbidities leading to significant losses in quality of life. Objectives: To evaluate the level of health literacy and the quality of life of patients with systemic arterial hypertension users of the Public Health System in a municipality in the Northeast region of Brazil. Methods: Cross-sectional analytical observational study carried out with 105 patients with SAH through the application of the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18), Short Test of Functional Health Literacy in Adults (S-TOFHLA) and the of Life Questionnaire in Arterial Hypertension (MINICHAL). Results: It was found that about 60% of the interviewed patients did not have adequate health literacy in both tests to measure the level of health literacy. It was found that some factors such as age, economic class and education were associated with inadequate health literacy (p < 0.01). In the assessment of quality of life, using the MINICHAL, 46.7% of patients reported that hypertension interferes with quality of life. It was also possible to show that the time of diagnosis and economic class influenced the quality of life of patients (p < 0.05). Conclusion: A relevant portion of patients with SAH did not have an adequate level of health literacy, which reflects the difficulty in understanding and processing health information and can impact the therapeutic management of the disease. 108986 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Amplatzer Cardiac Plug - (Abbott Vascular) Sizing for Occlusion of the Left Atrial Appendage Based on the Evaluation of the Landing Zone Measurements, Assessed by Three-Dimensional Reconstruction of the Computed Tomographic Angiography EDGARD FREITAS QUINTELLA1, Leonardo Hadid1, Marcio Jose da Costa Montenegro1, Luiz Kohn2, Dinaldo Cavalcanti Oliveira5, Gustavo Lycurgo4, Paulo Antonio Marra da Motta4, Maximiliano Otero Lacoste3 (1) Instituto Estadual de Cardiologia Aloysio de Castro (IECAC); (2) Universidade Estadual do Rio de Janeiro, Hospital Pedro Ernesto (HUPE); (3) Hospital Copa Star (Copa Star); (4) Hospital HOME; (5) Universidade Federal de Pernambuco (UFPE) Introduction: The left atrial appendage(LAA)percutaneous closure presents itself as a promising non-pharmacological alternative to anticoagulation. However, due to the anatomical singularity of the LAA, the accurate sizing and selection of the ideal prosthesis becomes a complex task. Objectives: In an attempt to mitigate the risks of inadequate sizing and to enable better standardized choice, this study proposes a new technique for sizing the Amplatzer Cardiac Plug prosthesis(ACP-AMULET)(Abbott Vascular). Methods: The current proposal was based on the consensus between experienced operators, who recommend that sizing should be performed by measuring the area and perimeter of the prosthesis landing zone(LZ), according to the measurements acquired by three-dimensional reconstruction of the LAA neck planes by Computed Tomography Angiography(CTA). In addition, a consolidated table was created from the manufacturer's recommended data, where the range of the different sizes and oversizing was accounted for to enable anchorage and safe implantation. Hence, after the proper sizing of the LZ measurements, the results are crossed with the table and choice is made with greater precision. Discussion: The rationale for the proposal derives from the irregularity and heterogeneity of the LAA shapes, making the use of bidimensional sizing methods based on the average of the diameters a less accurate decision-making criteria of prosthesis selection. Although TEE is still the most widely used method, it is also subject to biases such as echocardiographer experience and volume status, which may restrict the widespread treatment success when used as a stand-alone decision-making strategy. Moreover, by performing the choice through CTA, it allows a lower dependence of choice during the procedure, avoiding its possible biases. 108992 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Analysis of Gait Speed and Risk of Falls in the Elderly ANGELA SICHINEL1, JOLIANE ALVES DE MORAES ROTILLI,1, LUCI MATSUMURA1, MARILENA INFIESTA ZULIM1, LUCIANE PEREZ DA COSTA1, CLAUDIA GONCALVES GOUVEIA1, CAMILA SICHINEL SILVA DA CUNHA SOUZA1, MARIA LUCIA SALAMENE DE OLIVEIRA KROLL1, GABRIELLA P PELLIZZER1, MARCIA MARIA DA COSTA1, MATHEUS PORTOCARRERO PETERLINKAR1, ERIVALDO ELIAS JR1 (1) SAO JULIAO HOSPITAL-HSJ; (2) SAO JULIAO HOSPITAL-HSJ; (3) SAO JULIAO HOSPITAL-HSJ; (4) SAO JULIAO HOSPITAL-HSJ; (5) SAO JULIAO HOSPITAL-HSJ; (6) SAO JULIAO HOSPITAL-HSJ; (7) SAO JULIAO HOSPITAL-HSJ; (8) SAO JULIAO HOSPITAL-HSJ; (10) SAO JULIAO HOSPITAL-HSJ; (11) SAO JULIAO HOSPITAL-HSJ; (12) SAO JULIAO HOSPITAL-HSJ Introduction: The risk factors of falls in the elderly are consequences that occur due to internal or external changes; The internal modifications are those physiologically associated to the aging process, emphasising difficulties walking, lack of muscular strength, movement range restrictions, balance issues and lack of physical exercise; The external ones are those that depend on social or environmental circumstances that represent difficulties to the elder. Objective: To analyze the relationship between gait speed and the occurrence of falls amongst elderly that participate in the MAE Project (Multidisciplinary Assessment in the Elderly). Method: A cross-sectional study was carried out with 109 elderly individuals associated to the MAE Project, 72 of them (66,05%) being female and 37 (33,94%) being male. The data collection took place at the physiotherapy outpatient clinic of Sao Juliao Hospital, from April of 2017 to November of 2019, through application of the gait speed test, in which was measured the time, in seconds, the patient coursed the distance of 20 meters, not taking into account the 5 first meters because it is the acceleration period, nor the 5 last meters which is the deceleration period, and a questionary which contained name, sex and the question: Have you had falls in the last 12 months? Results: The sample was composed by 109 elders. 41 of those (37,6%) reported having falls in the last 12 months. Amongst those, 32 (78,04%) were female and 09 (21,95%) were male. Of the elderly that presented falls, 31 (75,60%) showed reduced gait speed, taking into consideration that the normal gait speed score, which ranges between 1,2 meters per second (m/sec) and 1,4 m/sec. Amongst the elderly with reduced gait speed, the female sex predominated with the number of 25 (80,64%) and average age of 70 years. Conclusion: Gait speed showed significative relationship with the occurrence of falls, being spotted reduced gait speed on more than half of the elders that had falls. However, when analyzing the study sample, in which less than half of the elderly has had falls, it was concluded that active elderly people have better results, that is, with the practice of physical activities, the functional capability increases and so the risk of falls is reduced. 108994 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Bnp Plasmatic as Predictor of Heart Failure Mortality in Study Cohort in South Brazil EDUARDO PITTHAN1, Vania Hirakata2, Juarez Barbisan2 (1) Universidade Federal da Fronteira Sul Passo Fundo; (2) Instituto de Cardiologia do Rio Grande do Sul Introduction: The diagnosis of HF in elderly patients in clinical basis is difficult due to comorbidities. The BNP is used as a diagnostic and prognostic tool in HF but is not sufficiently studied in the elderly. Hypothesis: To evaluate the association of plasma BNP levels with diagnostic accuracy of HF and longterm prognostic validation. Methods: Six hundred and thirtyfour consecutive patients presenting with suspected HF in the Emergency Room of a tertiary hospital in southern Brazil participated in this cohort study. All patients underwent BNP measurement (Biosite POCT) as the institution protocol were included between March 2008 and September 2014. Following the Gold Standard for diagnosis of HF consisting of history and physical examination ECG chest Xray echocardiogram Uni and Two Dimensional Color Doppler. The sample was divided into 3 groups: SHF (Systolic Heart Failure) HFPEF (Preserved Ejection Fraction Heart Failure) and NHF (No Heart Failure) and patients were followed for 78 months. The study endpoint was mortality identified by the certificate of death of the Mortality Information Service (SIM). Results: Most patients (59.6%) were female the mean age was 77 +- 8 years 40.5% over 80 years. The majority (46.8%) had a diagnosis of HFPEF and BNP median 335 pg/ml 25% presented SHF and BNP median of 573 pg/ml and 28% did not meet the criteria for NHF and median BNP 45 pg/ml (KruskalWallis's test p < 0.005). Half of the deaths were caused by HF. In the group with SHF was 79 deaths (49%) with a BNP median of 800 pg/ml and the 80 survivors median 383 pg/ml (p < 0.005). In HFPEF group occurred most deaths that computed 157 deaths (52% of the group) with a median of BNP 380 pg/ml and 140 survived with a median 245 pg/ml (p < 0,005). The NHF group had 40 deaths (22% of the group) with BNP median of 59 pg/ml and 138 survivors median of 36 pg/ml (p < 0,005). Survival analysis in 78 months (6.5 years) was performed by KaplanMeier curve. Two hundred seventh six deaths were recorded in the total group (42%). The group SHF with a 27month mean survival time (MST) the group HFPEF with a 52month MST the NHF group more than 50% survived. Conclusions: The BNP level showed association with the mortality index. BNP is an independent prognostic biomarker for longterm mortality in patients with HF in all ages. 109019 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Applicability of BNP as a Biomarker of Prognosis for Longterm Mortality in a Comparison between Non-Elderly, Elderly and Major-Elderly Patients in South Brazil EDUARDO PITTHAN1, Vania Hirakata2, Juarez Barbisan2 (1) Universidade Federal da Fronteira Sul Passo Fundo; (2) Instituto de Cardiologia do Rio Grande do Sul Introduction: Btype natriuretic peptide (BNP) is used as a shortterm biomarker for prognosis in patients with heart failure (HF). The prognostic role for longterm mortality is insufficiently studied. Hypothesis: To validate the BNP test as a biomarker of longterm mortality prognosis in patients with suspected HF, comparing the non-elderly 80 years old. Methods: The sample consisted of 634 patients with suspected HF, attended at the emergency room between March 2008 and September 2014. The efficacy of BNP to identify patients with heart failure and the association between the level of BNP (POCT Biosite) and longterm prognosis were evaluated. The study was divided into three age groups, Elderly (E) 60-79 years (46%), major-elderly >=80 years (38%) and Non-Elderly <60 years old. Cause of death was identified through a search of death certificates in registry offices, informed by the Brazilian Mortality Information System. Results: Most patients were white (93%), female (64%), with a mean age of 77 (+-8.6) years. HF was diagnosed based on a new gold standard that considered the Framingham and Boston criteria, plus echocardiography and ECG. HF was present in 340 patients (53%). Most of these patients (63%, n = 216) had HF with PreservedEjection (HFPEF). In bivariate analysis a BNP > 180 pg/ml was associated with a higher risk of mortality. In multivariate analysis BNP > 180 pg/ml remained associated with increased risk of mortality, with an HR of 3.4 (CI95%: 1.2 to 9.6;p80 years group with HF was 595 pg/ml, with a 27month mean survival time (MST) and 47% mortality rate. The median BNP for the Elderly between 60-79 years group was 369 pg/ml, with a 52month MST and 38% mortality rate. The Non-Elderly group BNP was 222 pg/ml, with an MST >50% and 26% mortality rate. Conclusions: The BNP level showed association with the mortality index. BNP is an independent prognostic biomarker for longterm mortality in patients with HF in all ages. 109029 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Triglycerides/HDL-Cholesterol Ratio in Patients Admitted to the Department of Cardiology of Hospital San Martin GRACIA LUZ DON1, Eugenia Machbeth1 (1) Hospital San Martin, Parana, Entre Rios, Argentina Dyslipidemia has been identified as the risk factor that has the greatest impact of suffering ischemic heart disease. Triglyceride/HDL-cholesterol ratio (TG/HDL-C) was proposed as the best marker of insulin resistance and is considered an atherogenesis marker. It is obtained from triglycerides (mg/dl)/HDL-cholesterol (mg/dl) calculation. The cutoff point of 3.0 correlates with insulin resistance and cardiovascular risk, >3.5 with small and dense LDL-C particles, coronary atherosclerosis and risk of myocardial infarction. The present study was conducted to evaluate the relationship between TG/HDL-C index and cardiovascular diseases that led to hospitalization in the Department of Cardiology of San Martin Hospital. Method Ninety-one patients admitted to the hospital over a four-month period were evaluated according age, gender, TG/HDL-C ratio (triglycerides in mg/dl and HDL-C in mg/dl), BMI, admission blood glucose, coronary lesions and discharge diagnosis Results 30 women, 59 men and two without declaring gender were analyzed. The highest concentration of patients corresponds to ages between 60 and 69. Risk factors of the studied population were: * Hypertension 66% * Diabetes Mellitus 25% * Smoking 20% * Dyslipidemia 19% * Overweight/obesity 67% Variable evaluated -Percentage TGL/HDL Index >3.5 IMC 25-29,9 51% IMC > 30 60% Admission Blood glucose 111-199 mg/dl 61% Admission Blood glucose >200 mg/dl 54% Severe coronary lesions >70% DA: 56% CX 72% CD 72% discharge diagnosis: ischemic heart disease 74% heart failure 48% Previous myocardial infarction 81% history of coronary artery bypass grafting or angioplasty 50% Dyslipidemic patients 52% Total evaluated patients 74% Conclusions TGL/HDL-C index >3/>3.5 is observed in hospitalized patients with high prevalence. This demonstrates the impact of insulin resistance and phenotype B on severe cardiovascular complications such as ischemic heart disease and heart failure. 109036 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Mitral Balloon Valvuloplasty: Risk Factors for Lack of Success, Severe Mitral Regurgitation and Major Complications IVANA PICONE BORGES DE ARAGAO1, Ricardo Trajano Sandoval Peixoto1, Rodrigo Trajano Sandoval Peixoto1, Caio Teixeira dos Santos1, Raul Ferreira de Souza Machado1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Sara Cristine Marques dos Santos1, Edison Carvalho Sandoval Peixoto1 (1) Universidade de Vassouras Background: Mitral balloon valvuloplasty is not Always successful and free from complications. Objectives: To determine the independent risk factors for an unsuccessful procedure, severe mitral regurgitation and major complications in mitral balloon valvuloplasty. Methods: Longitudinal prospective study of 518 mitral balloon valvuloplasties performed between July 6, 1987 and December 31, 2004, on 429 (82.8%) female patients and 89 (17.2%) male patients with a mean age of 37.5 +- 12.8 years. Major complications were considered to be: perforation with cardiac tamponade, stroke and severe mitral regurgitation per procedure. The continuous variables were transformed in categorical variables and the chi-square or Fisher exact tests to compare the categorical variables, and logistic regression and multiple logistic regression were used to identify independente factors for predicting success, incomplete procedure, severe mitral regurgitation and major complications. Results: Success was noted in 452 (94.2%) procedures, with major complications occurring in 22 (4.2%) patients, of which ten were severe mitral regurgitation; there were no per-procedure deaths, with four (0.8%) in-hospital deaths. In the multiple logistic regression, lower age predicted success in the procedure; the only variable that predicted an incomplete procedure was the initial period of the procedure, and a score >11 points predicted severe per-procedure mitral regurgitation. There was no independent predictor of major complications in this study. Conclusions: Success was related to younger patients, an incomplete procedure to the initial period of the procedure and severe per-procedure mitral regurgitation to an echocardiography score >11 points. 109044 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Women Self-Knowledge Screening for Cardiovascular Risk Factors in Different Age and Labor Actives Populations IVANA PICONE BORGES DE ARAGAO1, Livia Liberata Barbosa Bandeira1, Simone Aparecida Simoes1, Tatiana Soares Spritzer1, Caio Teixeira dos Santos1, Raul Ferreira de Souza Machado1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Sara Cristine Marques dos Santos1, Vanessa de Freitas Marcolla1 (1) Universidade de Vassouras Cardiovascular disease (CVD) may be clinically different in women compared to men being underdiagnosed and treated. Worldwide, CVD and stroke are the leading causes of death in females reporting 8.6 million deaths/year in the literature. The objective of this study was to identify the self-knowledge (SK) and prevalence (P) of risk factors (RF) for CVD and stroke in female populations of different age groups and work activities: students of basic cycle medical students (group MS), Police Pacifying Units Police (PPU) (group PPU) and government employees (group GE). Methods: Cross-sectional, observational study of P of RF for CVD and stroke in female populations of different ages and labor activities between: group GE-27/09/13 and 10/24/2013; group PPU-10/05/2013 and 10/10/2013; groups MS-06/2016 and 12/2016; through the filling of a similar and anonymous questionnaire with 30 objective questions of quick answers about SK of RF: age, stress level, smoking, hypertension (H), dyslipidemia, sedentary lifestyle, obesity, diabetes. weight, height. pregnancy, menopause, gynecological (G/Y) and cardiological/year (C/Y) consultations. A positive response or ignorance equaled one point. Considered a risk group: women with ~2 points for positive or unknown response. Results: A total of 961 women interviewed were divided into groups MS (total 159), PPU (602) and GE (200), respectively: mean age 20.62, 28.1 and 44.3; high stress 44%, 31%, without report; smoking 3.8%, 7.0%, 16%; H 2.5% (1.3% unaware), 7% (3%), 13% (3%); 76.7% had they cholesterol levels measured (10.0% total cholesterol >200 mg/dl and 33.3% did not know, 62.9% did not know HDL <40 mg/dl), 76.0% (7% and 59%, 87%), 95% (22% E 25%, 62%); 89.9% had measured blood glucose, 76%, 88%; S 45.3%, 53%, 36%; BMI calculated 88.7% (weight and height reported) 12.57% ;?25 and 0.0% ;?30, BMI 51% being 23% ;?25 and 0.0% ;?30 and 49% being 17% ;?25 and 8% ;?30; they did consultations G/Y: 79.9%, 90.0% 98% and C/Y: 7.54% 12% and 33%; score i?2: 98.75%, 97.0%, 74.0%. Conclusion: Most women, in different age groups and work activities, were at risk of developing CVD and stroke due to the high prevalence of RF or their lack of knowledge, after applying a similar questionnaire. It was highlighted the importance of primary prevention and awareness programs. 109046 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Mitral Valvuloplasty with Inoue Versus Balt Single Balloon. Results, In-Hospital Evolution and Cost Effectiveness IVANA PICONE BORGES DE ARAGAO1, Ricardo Trajano Sandoval Peixoto1, Rodrigo Trajano Sandoval Peixoto1, Caio Teixeira dos Santos1, Raul Ferreira de Souza Machado1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Sara Cristine Marques dos Santos1, Edison Carvalho Sandoval Peixoto1 (1) Universidade de Vassouras Objective: To compare the results, in-hospital evolution and cost of 468 percutaneous mitral balloon valvuloplasties (PMBV) with Inoue balloon (IB) and single Balt balloon (SBB). Methods: IB group (IG): 73 procedures and SBB group (BG): 395 performed between 06/1987 and 12/1999. Mean age: IG 37.1 +- 10.1 years and BG 37.3 +- 12.8 (p = 0.71745); 59 women in IG and 327 in BG (0.685255); NYHA functional class in IG and BG, respectively: I in 4 and 4 patients, II in 23 and 87, III in 40 and 265 and IV in 6 and 39 procedures (p = 0.010929). Atrial fibrilation: 7 in IG and 55 BG (p = 0.315511). Echocardiographic score 7.2 +- 1.2 IG and 7.3 +- 1.5 BG (p = 0.958911). Mitral valve area (MVA) Echo pre-PMBV: 0.98 +- 0.19 cm2 IG and 0.94 +- 0.21 BG (p = 0.143954). Results: Within-group comparison IG and BG, respectively: Pre-PMBV: mean pulmonar pressure (MPP) 33.9 +- 13.5 and 38.6 +- 14.3 mmHg (p = 0,007662); mitral gradient (MG) 17.3 +- 6.4 and 19.8 +- 7.0 mmHg (p = 0.013180); MVA Gorlin pre-PMBV 0.90 +- 0.20 and 0.91 +- 0.21 cm2 in BG (p = 0.8228449). Post-PMBV: MPP 25.3 +- 8.6 and 27.2 +- 10.6 mmHg (p = 0.261415); MG 5.9 +- 3.1 and 5.5 +- 3.7 mmHg (p = 0.083664); MVA Gorlin 1.98 +- 0.46 and 2.04 +- 0.40 cm2 (p = 0.419208). Complications: 5 cardiac tamponade in BG: 3 treated by surgery with 2 deaths, 2 with pericardial drenage without death. 1 stroke in BG. Severe mitral regurgitation (MR) 1 patient of each group, treated by surgery. Calculated cost of both technique 2 consecutive years with reuse and price of acquision at current prices demonstrated: IB technique U$1,286,32 and SBB U$309.94 for procedures. Conclusions: Both techniques were efficients. IG less symptomatic; MPP and MG were higher in BG; results post-PMBV were similar. MR were similar. Other complicaion only in BG. Lower cost for material acquisition in BG. 109047 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Prior Surgical Mitral Commissurotomy and Echocardiographic Score Influence in Mitral Balloon Valvuloplasty. Immediate Post Procedure Results IVANA PICONE BORGES DE ARAGAO1, Ricardo Trajano Sandoval Peixoto1, Rodrigo Trajano Sandoval Peixoto1, Caio Teixeira dos Santos1, Raul Ferreira de Souza Machado1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Sara Cristine Marques dos Santos1, Edison Carvalho Sandoval Peixoto1 (1) Universidade de Vassouras Introduction: Percutaneous mitral balloon valvuloplasty is effective in mitral stenosis. Objectives: To evaluate prior mitral surgical commissurotomy (PMC) and echocardiographic score (ES) in the results and complications of mitral balloon valvuloplasty (MBV). Methods: From 1987 to 2013, 526 procedures with Inoue balloon, double or single Balt balloon technique; 480 without PMC named primary MBV group (PMBVG) and 46 that have been submitted to PMC, the PMC group. The PMCG was older than PMBVG (42.7 +- 12.4 vs 36.9 +- 12.5 years, p = 0.0030). Gender, atrial fibrilation and NYHA functional class were similar. In PMBVG and PMCG, respectively, ES were 7.2 +- 1,4 and 7.7 +- 1.5 points (p = 0.0158) and mitral valve area (MVA) 0.94 +- 0.21 and 1.00 +- 0.22 cm2 (p = 0.0699). Results: Pre-MBV: mean pulmonary artery pressures (MPAP) were 37.8 +- 14.2 and 37.6 +- 14.4 mmHg, p = 0.9515; mean gradient (MG) 19.6 +- 6.9 and 18.3 +- 6.9 mmHg, p = 0.2342; MVA 0.90 +- 0.21 and 0.93 +- 0.19 cm2, p = 0.4092, respectively, whem compare PMBVG and PMCG. Post-MBV: MPAP were 26.8 +- 10.2 and 26.6 +- 10.9 mmHg, p = 0.9062; MG 5.4 +- 3.5 and 6.3 +- 4.2 mmHg, p = 0.1492; MVA 2.04 +- 0.42 and 1.92 +- 0.41 cm2, p = 0.0801, respectively. Mitral regurgitation (MR) were similar pre and post-MBV. Severe MR post-MBV in 10 patients: 8 in PMBVG and 2 in PMCG, p = 0.2048. As there were not found significant diferences, the total group were divided in ES <= 8 and >8 groups: Pre-MBV: MPAP 37.5 +- 13.9 and 39.3 +- 16.6 mmHg, p = 0.4041; MG 19.7 +- 6.8 and 18.3 +- 7.3 mmHg, p = 0.1753; MVA 0.90 +- 0.21 and 0.94 +- 0.20 cm2, p = 0.0090 respectively. Post-MBV: MPAP 26.7 +- 10.1 and 28.0 +- 10.6 mmHg, p = 0.3730, MG 5.5 +- 3.6 and 5.5 +- 3.3 mmHg, MVA 2.06 +- 0.42 and 1.90 +- 0.40 cm2, p = 0.0090. Conclusion: The groups with and without prior mitral commissurotomy in MBV were compare and no differences were found in post-procedure, as mean pulmonary artery pressure, mean mitral gradient, mitral valve area, and mitral regurgitation. Although PMCG was older, with higher ES, its hemodynamics datas were similar. Whem the entire group was divided based on echo scores, those with echo scores >8 had highse MV (p = 0.0090). and smaler mitral valve areas post-valvuloplasty. The valve anatomy were more important than prior commissurotomy. 109049 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Mitral Balloon Valvuloplasty: Single Versus Inoue Balloon. Long Term Follow-Up IVANA PICONE BORGES DE ARAGAO1, Ricardo Trajano Sandoval Peixoto1, Rodrigo Trajano Sandoval Peixoto1, Caio Teixeira dos Santos1, Raul Ferreira de Souza Machado1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Sara Cristine Marques dos Santos1, Edison Carvalho Sandoval Peixoto1 (1) Universidade de Vassouras Introduction: The single balloon (SB) is the less expensive technique to perform mitral balloon valvuloplasty (MBV). Objectives: This study aimed to demonstrate that MBV with the Balt single (BSB) and Inoue ballon, the wordwire accepted technique, had similar outcome and long-term follow-up (FU). Methods: From 1987 to 2013, 526 procedures were performed, being 312 with a FU, 56 (17,9%) with Inoue balloon (IB) and 256 (82,1%) with BSB. The mean FU 156 +- 144 months, p < 0.0001. Univariate analysis (UA) and multivariate Cox analysis (MCA) to determine independent predict variables of survival and event free survival (EFS) of death, cardiac surgery and new MBV, in both techniques groups. Results: In IB and BSB groups there were, respectively: female 42 (75.0%) and 222 (86.7%); mean age 37.3 +- 10.0 (19 to 63) and 38.0 +- 12.6 (13 to 83) years, p = 0.7138; sinus rhythm 51 (91.1%) and 215 (84.0%), p = 0.1754; echo score (ES) 7.6 +- 1.3 (5 to 10) and 7.2 +- 1.5 (4 to 14) points, p = 0.0528; echo mitral valve area (MVA) pre-MBV 0.96 +- 0.18 and 0.93 +- 0.21 cm2, p = 0.2265; post-MBV mean MVA (Gorlin) were 2.00 +- 0.52 and 2.02 +- 0.37 cm2, p = 0.9554; MBV dilatation area 6,09 +- 0,27 and 7,02 +- 0,30, p < 0,0001. At the end of the FU, there were in IB and BSB groups, respectively: echo MVA 1.71 +- 0.41 and 1.54 +- 0.51 cm2, p = 0.0552; new severe mitral regurgitation in 5 (8.9%) and 17 (6.6%) patients, p = 0.5633; new MBV in 1 (1.8%) and 13 (5.1%), p = 0.4779; mitral valve surgery in 3 (5.4%) and 27 (10.4%), p = 0.3456; deaths 2 (3.6%) and 11 (4.3%), p = 1.000; cardiac deaths 1 (1.8%) and 9 (3.5%), p = 1.000; ME 5 (8.9%) and 46 (18.0%), p = 0.1449. In UA and MCA the BSB or IB technique do not predict survival or EFS. The independent risk factors to survival were: age <50 years (p = 0.016, HR = 0.233, 95% IC 0.071-0.764), ES <= 8 (p < 0.001, HR = 0.105, 95% IC 0.34-0.327), MBV dilatation area (p < 0.001, HR 16.838, 95% IC 3.353-84.580) and no mitral valve surgery in the FU (p = 0.001, HR0.152, 95% IC 0.050-0.459). Independent risk factors to EFS: no prior commissurotomy (p = 0.012, HR = 0.390, 95% IC 0.187-0.813) and post-MBV MVA >= 1.50 cm2 (p = 0.001, HR = 7.969, 95% IC 3.413-18.608). Conclusion: In 25 years, survival and EFS were similar in BSB and IB technique. Independent predictors of surviva: age < 50 years, ES <= 8 points, MBV dilatation area > 7 mm2 and no mitral valve surgery in the FU. Independent predictors of EFS: no prior commissurotomy and post-MBV MVA >= 1.50 cm2. 110916 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Assessment of Lipoprotein(A), Apolipoprotein B, Apolipoprotein A-1, and Apo B/Apo A1 Ratio in Predicting the Severity of Premature Coronary Artery Disease (CAD) in North India SATYENDRA TEWARI1, SOHAM CHAUDHARI2, ANKIT SAHU3, ROOPALI KHANNA4, SUDEEP KUMAR5, NAVEEN GARG6, ADITYA KAPOOR7 (1) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (2) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (3) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (4) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (5) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (6) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India); (7) Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (India) Introduction: CAD is one of the principle cause of mortality and morbidity. Considerable data suggests involvement of Lipoprotein (a), apolipoprotein B, apolipoprotein A-I, its ratio and abnormal lipids. Objectives: To compare the risk factor profile, clinical presentation, and angiographic severity of CAD in young patients (Age <= 45 years) and elderly patients (Age > 45 years). To correlate the level of Lipoprotein (a), Apolipoprotein (a), Apolipoprotein (b) and Apo B/Apo-A1 with the angiographic severity of CAD. Methods: This a retrospective, observational, single-centre study performed at tertiary care hospital. Angiographically proven CAD patients of all age groups were enrolled. Results: In our study, 714 patients (12.49%) belonged to group 1 (age <= 45 years) and 5003 patients (87.51%) belonged to group 2 (age > 45 years). Mean value of age(years) of study subjects was 56.92 +- 9.8. Distribution of gender was comparable between age group <=45 and >45 years. (Female:- 17.23% vs 17.49% respectively, Male:- 82.77% vs 82.51% respectively) (p value = 0.863). Proportion of patients with number of vessels involved:- 1 (single vessel) was significantly higher in age group <=45 years as compared to >45 years (1:- 79.97% vs 76.31% respectively). Proportion of patients with number of vessels involved:- 2 (double), 3 (triple) was significantly lower in age group <=45 years as compared to >45 years (2:- 19.33% vs 21.75% respectively, 3:- 0.70% vs 1.94% respectively). (p value = 0.017) There is statistically significant rise in the level of Lp (a) (mg/dL) and Apolipoprotein B/Apolipoprotein A-1 ratio with number of vessels involved in age group <=45 years and >45 years (p value < .05). Conclusion: Elevated Lp(a) is strongly associated with the development of high-risk vulnerable plaques that are prone to rupture. The ratio of Apo B to Apo A-I represents the ratio of total atherogenic to antiatherogenic lipoproteins. We observed a gradual increase in Lp(a) and Apo-B/A1 levels with the increasing number of stenotic vessels and an independent association between Lp(a) and Apo B/Apo A-1 with the severity of CAD after adjusting for other possible confounding factors. Effort should also be made to assess the atherothrombotic risk due to the Lp (a) particles on one hand and to apolipoproteins on the other hand. It is also essential that Lp (a), apo B, and ratio of abo B/apo A as an independent risk factor should be integrated into the treatment guideline. 109096 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence and Risk Stratification of Chronic Kidney Disease in a Tertiary Cardiology Hospital: A Cross-Sectional Study FARID SAMAAN1, Gianna Mastroianni Kirsztajn2, Ricardo Sesso2 (1) Instituto Dante Pazzanese de Cardiologia; (2) Universidade Federal de Sao Paulo Introduction: Chronic kidney disease (CKD) is common, preventable and silent in its early stages. Therefore, early detection of this condition in the population at risk, through laboratory tests, is essential. Objectives: To estimate the CKD prevalence and perform its risk stratification in a tertiary health service specialized in cardiology. Methods: The study was cross-sectional and based on laboratory records of patients from a public hospital specialized in cardiology. The evaluated tests were serum creatinine and urinary albumin/creatinine ratio (ACR, random sample) performed on an outpatient basis between 01/01/2021 and 12/31/2021. Duplicate exams and patients under 18 years of age were excluded. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI creatinine equation. CKD was defined by eGFR <60 ml/min/1.73 m2 and classified into the following stages: 3a (45-59 ml/min/1.73 m2), 3b (30-44 ml/min/1.73 m2), 4 (15-29 ml/min/1.73 m2) and 5 (<15 ml/min/1.73 m2). Albuminuria was classified into three levels: A1 (<30 mg/g), A2 (30-300 mg/g) and A3 (>300 mg/g). According to the CKD risk map, individuals with simultaneous creatinine and ACR measurements were stratified into low, moderate, high or very high risk. Results: The sample consisted of 36,651 patients in whom the same number of serum creatinine results and 19,031 ACR results were evaluated (median patients' age 72.5 [51.0-73.6] years, 51.3% male). The prevalence of CKD was 30.9% and patients with stages 3a, 3b, 4 and 5 corresponded to 15.3%, 10.2%, 3.6% and 1.7%, respectively. CKD was more frequent in older age groups: 18-29 years (2.5%), 30-44 years (8.4%), 45-59 years (25.5%), 60-74 years (30 .7%) and >=75 years (56.8%) (p < 0.001). Patients with albuminuria categories A1, A2 and A3 were 71.5%, 22.6% and 5.9%, respectively. ACR >= 30 mg/g was not associated with age: 18-29 years (23.3%), 30-44 years (23.4%), 45-69 years (26.0%), 60-74 years (28 .5%) and >=75 years (36.9%) (p = 0.671). Patients with simultaneous measurements of serum creatinine and ACR were 19,031 and their distribution in the CKD risk categories was: low (52.0%), moderate (23.8%), high (13.1%) and very high risk (11.2%). Conclusions: The results showed that CKD is present in about 30% of the patients assisted in the cardiology institute evaluated. In up to half of the patients, the risk of major outcomes such as hospitalization, need for renal replacement therapy, and death was moderate, high, or very high. 109100 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Pulmonary Vascular Remodeling in Monocrotaline-Induced Pulmonary Arterial Hypertension: Morphometric Analysis LUIZ FERNANDO KUBRUSLY1, Douglas Mesadri Gewehr2, Jessica Ferreira Eduardo1, Izabele Maria Geri1, Allan Fernando Giovanini1, Fernando Bermudez Kubrusly3 (1) Mackenzie Evangelical School of Parana, Curitiba, Parana, Brazil; (2) Denton Cooley Institute of Research, Science and Technology, Curitiba, Parana, Brazil; (3) Curitiba Heart Institute, Curitiba, Parana, Brazil Introduction: Pulmonary arterial hypertension (PAH) is a high severity vascular disorder with fast progression, which clinical spectrum is related to the reduction of the pulmonary arteries lumen with an increase in pressure and vascular resistance. These changes result from many mechanisms such as medial hypertrophy, concentric intimal fibrosis and necrotizing vasculitis, which are responsible for the remodeling of pulmonary artery wall, the reduction of pulmonary compliance and leads to cardiac muscle overload. Objective: To evaluate the severity of pulmonary arteriopathy in an animal model of Monocrotaline-induced Pulmonary Arterial Hypertension, through histological morphometric analysis of pulmonary vessels. Methodology: Morphometric analysis was performed in Zen 3.2 Software and 50 PAH animal model slides, with random selection of 10 arterioles and 10 pulmonary non-arteriolar vessels for each animal. The gravity was delimited through three pulmonary systems elements (1) medial layer thickness, (2) microvascular muscularization of non-muscle vessels, and (3) obliteration of muscle arterioles and non-muscle vessels. We also assess cardiac overload thought right ventricular freewall thickness and the right ventricular chamber area. Results: There was a gradual onset of pulmonary disease in MCT animals, whose evolution was followed by histological findings of pulmonary arteriopathy, including arterioles' muscularization, medial layer hypertrophy, concentric and "plexiform-like" laminar and non-laminar neointimal lesions. There was an important increase in the thickness of the tunica media and the degree in microvascular muscularization through the experimental groups compared with the control. There was a significant increase in luminal obliteration of muscle arterioles and non-muscular vessels, measured by the luminal obliteration ratio. The right ventricular hypertrophy (HVD), assessed by measuring the thickness of the right ventricle, had increased significantly on 30-to-37-day groups, represented almost twice the value of the control group. Besides that, there was a significant dilatation of the Right Ventricular Chamber on 30-to-37-day groups. Conclusion: The MCT application proved the effective inducing PAH, being able to generate changes in vessels through the lower exposure group. Furthermore, lungs lesions are intensified over time, and the observation of plexiform lesions were not registered in a similar model. 109135 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Algorithm for Identification of Limitations of Life Activities in Individuals with Heart Disease: Validation for the Brazilian Population ROMERO HENRIQUE DE ALMEIDA BARBOSA1, Emerson Silva de Jesus1, Eldys Myler Santos Marinho1, Johnnatas Mikael Lopes1 (1) Universidade Federal do Vale do Sao Francisco Background: Heart disease burdens individual health, limiting life activities such as people's productive capacity and quality of life. In addition to understanding the clinical characteristics of heart diseases, identifying subjects at risk prior to the installation of limitations helps in directing preventive therapeutic and multiprofessional actions. Objective: To develop an algorithm to screen people with heart disease in an outpatient setting for their risk of future functional life activity limitations (LAL). Methods: Cross-sectional study with data from the 2019 National Health Survey in Brazil. The general sample consisted of 90846 interviews, being selected individuals aged 18 years and some type of heart disease diagnosed for more than a year by physicians. The outcome was current usual LAL due to the disease. Independent variables were grouped into cardiac, self-care and social morbidities. The data were analyzed using the CHAID-type decision tree algorithm, and the sample was divided into training (70%) and testing (30%). Sensitivity (S), specificity (SP), positive (PV+) and negative (PV-) predictive values for the outcome were estimated. Results: 4711 (5.3%;95%CI: 5.0-5.6) individuals have a diagnosis of heart disease, of which 4409 (94.4%; 95%CI:93.4-95.3) have been diagnosed for more than one year and mean age of 59.31 (95%CI: 58.31-60.31) years. 2374 (49.2%; 95%CI 46.5-51.8) of those with heart disease reveal LAL. 2830 observations were used to train the algorithm and 1171 to test it. Five attributes remained in the final model, two of morbidity, two of self-care and one of social, generating 13 nodes and a thickness of 3 in the decision tree. An algorithm with S = 81.9%, SP = 43.2%, PV+ = 58.94%, PV- = 70.54% was obtained. In the test, S = 83.8%, SP = 43.6%, PV+ = 60.67% and PV- = 72.04%. Conclusion: The algorithm has a relevant rate of true positives, however it has a low rate of true negatives for LAD. As the damage caused by LAL and its high prevalence are much greater than the damage caused by the provision of care and follow-up, its application in clinical and community contexts in Brazil is justified. 109138 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Morphological and Morphometrical Aspects of the Aortic Wall in Equine (Equus Caballus, L. - 1758) LUCIANO DE MORAIS PINTO1, Marcelo Jose Bock1, Vitor Pires Pereira1, Marcelo Leite da Veiga2, Claudia de Melo Bertoncheli dos Santos3, Luciano de Morais-Pinto1 (1) Laboratorio de Design Anatomico - Universidade Federal de Santa Maria; (2) Laboratorio de Morfofisiologia Experimental - Universidade Federal de Santa Maria; (3) Laboratorio de Anatomia Patologica - Hospital Universitario - Universidade Federal de Santa Maria Aortic rupture is relatively common in horses. However, architectural differences have not yet been considered in the pathogenesis of aortic catastrophe in this species. Thus, our objective was to describe the morphological and morphometric aspects of the tunica intima (TI) and media (MT) in the aortic bulb (AB) and ascending aorta (AA). 52 healthy aortas from adult horses were processed according to standard optical and scanning electron microscopy protocol. TI and TM thickness as well as aortic lamellar units were digitally measured. The aorta was pale yellow and had a rigid texture and distinct thicknesses. The AA wall was thicker than the BA, in totality and in the thickness of the layers (Tab.1). The lamellar units were better defined in AA and arranged in interleaved layers of elastic lamellae, smooth muscle cells and collagen fibers, while in BA the trilaminar aspect was not maintained and the muscle tissue bands were arranged in mosaic. The increase in the thickness of the aortic wall in the BA-AA direction suggests that blood flow is clockwise helical. It is assumed that blood pressure was higher in the septal AB for the left AA; from left BA to right AA and from BA to septal AA. As dissection/rupture involves failure of tissue structure, it is expected that a better understanding of the normal tissue architecture of the aorta in horses will contribute to future studies of the pathogenesis involving aortic catastrophes in animals and humans. 109147 Modality: E-Poster Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE The HDAC Inhibitor Valproic Acid (VPA) Reduces Heart Damage of the Shr (Spontaneously Hypertensive Rat) Through Epigenetic Cardiac-TRH Modulation SILVIA INES GARCIA1, Maria Silvina Landa1, Maia Aisicovich1, Mariano Luis Schuman1, Ludmila Soledad Peres Diaz1, Graciela Giardino2, Carlos Jose Pirola1, Silvia Ines Garcia1 (1) Molecular Cardiology Laboratory, Institute of Medical Research-IDIM University of Buenos Aires-CONICET; (2) Experimental Medicine Laboratory, Hospital Aleman, Buenos Aires Cardiac TRH (cTRH) induces cardiac damage and its inhibition attenuates heart injury in different models: SHR and cTRH overexpression (Schuman 2011,2014); Angiotensin II infusion and doxorrubicin cardiotoxicity (Peres Diaz 2018,2020) and LVH induced by obesity or leptin infusion (Aisicovich 2019,2021). We described that cTRH inhibition increase LVEF% and preserve cardiac function after acute MI in rats (Schuman 2021). Histone acetylation (HDACs) modulates gene expression by epigenetic alterations as DNA methylation. VPA, an FDA approved drug for bipolar disease and epilepsy, protects heart against MI injury (Tian 2019). As VPA is an inhibitor of HDACs, we hypothesized that inhibition of HDACs with VPA might attenuate LVH and fibrosis in SHR by the modulation of cTRH. 7 w-old male SHR and WKY received VPA and hearts were used after 10w of treatment. BP, LVH index and cTRH expression significantly increased in SHR. VPA slightly attenuated (p < 0.05) the higher SHR BP, without effect in WKY. LVH index decreased (p < 0.05) only in SHR. LVPWT significantly decreased (p < 0.05) only in SHR. As hypothesized, VPA normalized cTRH mRNA expression in SHR (WKY = C:0.61 +- 0.7vs VPA:0.41 +- 0.97; SHR = C:5.72 + 0.9 vs VPA:0.61 + 0.9, p < 0.05) and TRH IHQ confirmed these results (p < 0.05) which brought a strong reduction in fibrosis in LV, by decrease in BNP and 3-collagen expression in SHR+VPA. This was confirmed by Masson's an d Sirius Red stainings (p < 0.01). SHR offspring born from VPA-treated parents with a 2-week washout period before mating, wich never received VPA, surprisingly had a significant decrease in hypertrophy (LVW/BW) vs offspring of both SHR untreated parents, showing a transgenerational inheritance. Indeed, SHR showed a decrease in % TRH promoter methylation (Increase in gene expresion) that is significantly reverted in offspring of VPA treated parents (methylation-specific PCR). Consistently, we observed a decrease in cTRH expression (p < 0.05), and therefore, a significant reduction (p < 0.05) in BNP and type 3 Collagen expression, despite the high BP in VPA parents offsprin. To sum up, we described for the first time that VPA treatment modulates cTRH gene and consequently attenuates heart fibrosis and hypertrophy in the SHR, without affecting BP. We show an epigenetic modulation of VPA over cTRH promoter that could be responsible not only of cardiac alterations during VPA treatment, but beyond affecting next generation with results still unknown. 109150 Modality: E-Poster Researcher - Non-case Report Category: NUTRITION Relationship between Obesity and Cardiovascular Diseases in Adults with Obstructive Sleep Apnea Syndrome (OSAS) RENATA BORBA DE AMORIM OLIVEIRA1, Renata Borba de Amorim Oliveira1, Ingrid Beranger da Costa Pereira1, Ana Paula Menna Barreto1, Monica Feroni de Carvalho1 (1) Centro Multidisciplinar UFRJ-Macae Obstructive Sleep Apnea Syndrome (OSAS) is a very common disorder of breathing during sleep, characterized by recurrent episodes of total interruption (apnea) and/or partial interruption (hypopnea) of ventilation resulting from collapse of the upper airways. Obesity, systemic arterial hypertension and cardiovascular diseases are risk factors of the disease, being related to a major risk of morbidity and worsening of the already installed disorder. The objective of study was to assess the frequency of obesity by different anthropometric measures of total and central body adiposity in adult individuals with OSAS, and its association with excessive daytime sleepiness and severity of the syndrome. The present study was a prospective observational study, in which adults who underwent polysomnography for the diagnosis of OSAS were evaluated. Were evaluated variables: socio-demographic, sleep-related complaints, degree of daytime sleepiness, which was evaluated by the Epworth Sleepiness Scale developed by Johns (1991) and validated in Brazil by BERTOLAZZI et al. (2009), and also to risk factors for OSAS and anthropometric: weight, height, Body Mass Index (BMI) and Waist Circumference (WC). In the 64 patients evaluated, only 43 subjects (67.2%) were diagnosed with OSAS and entered the study. Regarding the classification of OSAS, 44.2% presented mild degree, 23.2% moderate and 32.6% severe degree. Excessive Daytime Sleepiness (EDS) was present in 72.1% of the patients. The classification by BMI is 11.6% of eutrophy, 18.6% of overweight, 25.6% of obesity grade I, 27.9% of obesity grade II and 16.3% of obesity grade III. Regarding the classification of WC, 62.8% presented a much increased risk. Analyzing the morbidity profile of the studied population, 39.50% had systemic arterial hypertension and 11.60% cardiovascular disease. There was a statistically significant association between obesity and WC (p = 0.001), otherwise was not found between obesity and severity disease (OSAS) (p = 0.76) or with SDE (p = 0.127). To conclude, the studied group presented high prevalence of obesity, arterial hypertension and cardiovascular diseases and changes in weight and in the health condition are important to manage symptoms and aggravation of the OSAS and cardiovascular disease. 109167 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cardioprotective Effect of Cannabidiol (CBD) in Cardiomyopathy and Heart Failure. From their Molecular Pathways to Clinical Translation GERARDO GARCIA-RIVAS1, Omar Lozano1, Christian Silva-Platas1, Judith Bernal-Ramirez1, Hugo Alves1, Carlos Jerjes-Sanchez1, Guillermo Torre-Amione1 (1) TECNOLOGICO DE MONTERREY Increasing evidence points to CBD as a promissory therapeutic molecule for diverse inflammatory pathologies, including cardiovascular diseases such as coronary disease and myocarditis. Our study evaluates the application of CBD as a potential therapy for heart failure (HF). Here we assessed the cardioprotective effects of CBD administration in a non-ischemic HF model in mice. Every 3rd day a dose of 1 mg/kg of synthetic CBD was administered via a subcutaneous injection. After four weeks of treatment, the animals were euthanized, and their heart was collected for further analysis. Fibrosis development and myocyte hypertrophy was determined by histopathologic imaging quantification. Additionally, to explore the CBD-antihypertrophic mechanisms, we used cultured cardiomyoblasts to explore the role of cytosolic and mitochondrial oxidative stress and NF-kB pathway intermediates. We developed a multi-center, double-blind, placebo-controlled, randomized trial for the clinical translation, considering the preclinical data. The primary objective of this study is to evaluate the effect of CBD on the prevention of cardiovascular and COVID-19 complications in patients hospitalized for COVID-19. We observed a significant reduction of fibrosis and cell hypertrophy in CBD-treated animals. The expression by qPCR of BNP and collagen1 as a pathological remodeling marker was significantly reduced when CBD was administered in contrast with the HF mice. Pro-inflammatory cytokines expression was observed in IL1b and IL6 expression. At the cellular level, a significant reduction in cell area was observed in CBD treated groups even when exposed to Ang II, achieving sizes comparable to those of the controls. CBD significantly reduced the generation of mitochondrial ROS entities in our hypertrophy model and showed an increase in NF-kB activation that can be reversed by CBD treatment. Also, CBD normalizes the expression of mechanical stress and remodeling markers such as BNP, TGFa, SOD2, IL6, and IL10 involved in inflammation. 23 Non-critical patients hospitalized within the previous 48 hours who tested positive for COVID-19 within seven days and have a prior history of cardiovascular disease (CVD) and significant risk factors for CVD were enrolled. Preliminary results indicate the safety of CBD in patients with COVID-19 infection and cardiovascular disease. 109186 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Usefulness of Strain in Chagas Disease in Patients with Ventricular Arrhythmia and Normal Ejection Fraction NATALIA CARRO1, Graciela Maria Rousse1, Cabrejos Gustavo1, Matilde Del Campo Contreras1, Leandro Parrilla1, Nudelman Ezequiel Adolfo1, Rubio Edgardo1 (1) Division of Cardiology. Echocardiography Laboratory, Hospital of the Government of the city of Buenos Aires Introduction: Global Longitudinal Strain (GLS) is a sensitive method for the early detection of myocardial damage. The latest AHA classification of Chagas disease (ChD) includes, in stage BI, a population with preserved Ejection Fraction (EF) heterogeneous due to ECG changes and/or segmental wall motion abnormalities. The evaluation of abnormal Segmental Longitudinal Strain (SLS) and its comparison with MRI has not been sufficiently evaluated in this population. Objective: In patients (p) with ChD in Stage BI the aim was1)To evaluate the usefulness of GLS in comparison with p with the indetermined form of ChD or Stage A 2) To compare abnormal SLS with cardiac MRI in detecting the anatomical substrate of the arrhytmia. Methods: Transversal, monocentric study. 55p were included January 2018-March 2020: 17p with ChD in Stage B1 with frequent ventricular arrhythmia, cardiac Echo-Doppler with Longitudinal Strain assessment, and gadolinium-enhanced cardiac MRI (Group B); they were compared with 38 p Stage A of ChD (Group A). The association between Strain and abnormal cardiac MRI in group B patients was analyzed. Results: 2 p were excluded due to inadequate ultrasonic image quality. The p from Group B compared to those from Group A were older, had higher Left Atrial volume, lower MAPSE, lower TDI, lower absolute value of GLS (18.3 +- 2.3% stage B vs 21.81 +- 2.5% stage A, p < 0.001) and similar EF. Through ROC curve between group A and B patients, the best cut-off point GLS was determined, a value of -20.5% with sensitivity of 93% and specificity of 70%, and area under the curve of 0.83 CI 95% (0.71-0.95). A cardiac MRI was performed in 11 out of 16 p; in 6 of them it was abnormal: due to late enhancement (4 p), edema plus enhancement (1 p), and thinning and akinesia (1 p). 5 of the 6 p with pathological cardiac MRI presented abnormal SLS and none of the p with normal cardiac MRI. The association between cardiac MRI alterations and SLS abnormal evaluated by means of the Kappa index was 0.82. Conclusions: In our limited population: 1.GLS was significantly lower in in group B1.2. The accurate association between cardiac MRI and abnormal SLS shows the latter as a useful alternative for the diagnosis of the anatomical substrate of arrhythmia. 109181 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Randomized Comparison between Ultrasound Guided Axillary Vein and Cephalic Cutdown for Cardiac Stimulation Devices Implantation RITA ELIZABETH IBARRA CASTILLO1, JORGE LUIS ARBAIZA SIMON2, JOSE LUIS LASO BAYAS1 (1) Hospital de Especialidades Carlos Andrade Marin; (2) Hospital Vozandes Quito HVQ Introduction: Cephalic vein cutdown (CVC) and subclavian vein puncture are the most widely used techniques for leads insertion during the implantation of cardiac stimulation devices (CSD). Lately, axillary vein access (AVA) has emerged as an alternative. Many approaches have been described for AVA, including the ultrasound (US) guided technique which seems to be fast and safe. objective: Our purpose was to assess whether the US guided puncture of the axillary vein was as efficient as the CVC for CSD implantation. Methods: This was a multicenter prospective trial. All patients undergoing first pacemaker or implantable cardiac defibrillator implantation were submitted to an US scanning of the site of implantation to determine if the axillary vein was visible. Only those with a clear axillary vein were included. None of the operators had previous experience in US AVA. All procedures were planned as ambulatory. We randomized 76 patients to either US AVA (n = 38) or CVC (n = 38). We included only patients with CSD with <=2 leads. Primary endpoint was success in introducing all the intended leads through the selected access. Secondary endpoints were: complications during the first week after the implantation, time of fluoroscopy, duration of the procedure, use of local and general anesthesia and need of hospitalization. We used X squared and T-tests to compare results from categorical and continuous variables. Analyses were performed according to the intention-to-treat principle. Results: There were no differences in the demographic characteristics. The mean age of all patients (n = 76) was 70.8 years, with 56.6% (n = 43) being male. In the AVA group, access success was achieved in all the subjects (n = 38), and in 78.9% of patients (n = 30) the vein was gained with US. The mean of attempts to gain the first access was 1.8. In the CVC group, the access success was lower, 76.3% (n = 38, p = 0.002). Regarding the rate of complications, there were no differences (AVA 5.2%, CVC 7.8%; n = 76, p = 0.64). Furthermore, we found no differences in time of X-ray exposure, procedure duration, quantity of local anesthetic used, need of general anesthesia or hospitalization (n = 76, p > 0.05). Conclusion: We found that, in comparison to CVC, US AVA was a more efficient technique, allowing successfully insertion of all leads from a conventional bicameral CSD, without increasing complications or issues of the implantation procedure. Our results are in concordance with other randomized clinical trials. 109233 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Melatonin and NLRP3 Deficient Mice Protect Heart Mitochondria from Aging. Role of NRF2 MIGUEL MEIRA E CRUZ1, Germaines Escames2, Jose Fernandez Martinez2, Dario Acuna Castroviejo2 (1) Centro Europeu do Sono; Sleep Unit, Centro Cardiovascular da Universidade de Lisboa, Lisbon, Portugal; (2) Centro de Investigacion Biomedica, Departamento de Fisiologia, Facultad de Medicina; Instituto de Biotecnologia, Universidad de Granada, Spain Introduction: Cardiovascular diseases (CVD) constitute the leading cause of death in the world, and aging is by far the major risk factor for cardiac dysfunction. Aging involves subclinical inflammatory activation, with NF-kb and NLRP3 inflammasome as the main components of such response. But inflammation also induces a pro-oxidative response, responsible for the oxidative damage to the cell and mitochondria, leading to a bioenergetic failure. In turn, melatonin exerts profound anti-inflammatory and antioxidant properties, with the mitochondria as the main intracellular target. Here, we analyzed the impact of the NRLP3 inflammasome in the myocardial aging and the role of melatonin in preventing it. Methodology: For this study, we used wild-type and NLRP3-deficient mice of 3, 12, and 124 months of age, with and without melatonin treatment. Results: The absence of NLRP3 prevented the age-dependent myocardial failure and mitochondrial impairment, affecting the Bax/Bcl2 ratio. The Nef2-dependent antioxidant response was unaffected by the lack of NLRP3. In wild-type mice, melatonin treatment produced counteract the age-dependent damage, providing similar protective features than the absence of NLRP3. Melatonin also improved mitochondria structure and enhances the Nrf2 antioxidant response. Conclusions: NLRP3 inflammasome-dependent chronic inflammation during ageing is main responsible for myocardial loss of function, causing proapoptotic phenomena, free radicals' formation and oxidative damage, and mitochondrial bioenergetic deficit, suggesting a molecular target for cardiac protective therapies. Melatonin, which reaches all subcellular compartment of the myocardial, blocks the NLRP3 inflammasome response and maintains the integrity of the heart, doing it a drug of choice for this age-dependent preventive therapy. 109239 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Correlation of Left Atrial Volume Increase with Ischemic Stroke and Transient Ischemic Attack KLEIBER MARCIANO LIMA BOMFIM1, Alan Alves de Lima Cidrao1, Pedro Braga Linhares Garcia1, Leonardo Miranda Macedo1, Jose Doriberto Freitas1, Giovanna Rolim Pinheiro Lima1 (1) HOSPITAL REGIONAL DO SERTAO CENTRAL Introduction: Stroke is one of the main causes of morbidity and mortality, currently representing the second leading cause of death worldwide. Regarding the etiologies, the cardioembolic type is responsible for 14 to 30% of the ischemic cases and presents higher mortality and worse functional complications. In terms of structural heart diseases, the increase in left atrial volume is an independent factor for stroke, in which the chance of thromboembolism is 20% per year. Objective: To evaluate left atrial volume increase, determined by transthoracic echocardiographic study, as an independent variable for risk of ischemic stroke and transient ischemic attack. Methods: This is a quantitative descriptive, cross-sectional, prospective cohort study conducted between April 2020 and April 2021 in the stroke unit of a tertiary public hospital. Data analysis was performed using the statistical package SPSS, version 22 (IBM - 2017), in which it was possible to perform descriptive analysis to characterize the sample, student's t test for independent samples, correlation analysis and simple linear regression. The calculation of the left atrial volume was performed by two-dimensional echocardiography in the apical projections of two and four chambers, indexed by the body surface. Results: The study included 308 patients from the State of Ceara who had ischemic stroke and transient ischemic attack. Age ranged from 50 to 98 years (M = 72; SD = 10.8), being 53.7% male and 46.3% female. Most had a diagnosis of ischemic stroke 93.9% and 6.1% transient ischemic attack. Results revealed that the variable "left atrial volume" did not have a normal distribution (K-S (308) = 0.46, P < 0.05; S-W(308) = 0.55, P < 0.05). The Pearson correlation analysis between left atrial volume and diagnosis of ischemic stroke/transient ischemic attack evidenced a positive linear correlation (0.021). Conclusion: The present data demonstrate a positive correlation between increased left atrial volume and the occurrence of ischemic stroke/transient ischemic attack. 110338 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Atropine Test in Predicting Cardioneuroablation Results JC PACHON-M1, Enrique I. Pachon-M1, Juan C Zerpa-Acosta2, Carlos TC Pachon2, Tomas G Santillana-P1, Tasso J Lobo2, Felipe A Ortencio2, Ricardo C Amarante1, Juan C Pachon-M1 (1) Sao Paulo University; (2) Sao Paulo Heart Hospital; (3) Semap Arrhythmia's Service Background: Vagal tone predominates most of the time. Therefore, isolated sinus heart rate(HR) is higher than the in-situ sinus rate. Atropine stops vagal action by blocking muscarinic receptors. Cardioneuroablation (CNA) also abolishes vagal action by eliminating the postganglionic vagal neuron, causing HR increase. Knowing previously whether HR will increase with CNA is very important since CNA is not indicated if there is no atropine response. Objective: To assess the correlation between HR and Wenckebach point(PW) determined by the atropine test (AT) and that one resulting from CNA. Methods: 76p, 41 females (54%), 14-67 (37 +- 13.2) years, with reflex functional bradyarrhythmias (neurocardiogenic syncope) or non-reflex (sinus dysfunction, vagal AF or bradytachycardia) submitted to CNA controlled by extracardiac vagal stimulation. AT was performed with IV infusion of 0.04 mg/kg. CNA was performed by ablation of the P-point, the presumed 4 main GPs areas and spare AF-Nests, at least 02 days post-AT. The maximum HR and PW obtained under the atropine and at the end of the CNA were compared. Results: There were significant HR and PW increases with atropine and with CNA. The increases were smaller with CNA probably because CNA also eliminates sympathetic fibers and AT does not. Conclusion: There is a strong correlation between HR and PW determined by atropine and those resulting of CNA. Thus, atropine test can be used as a good predictor of the CNA result. 110339 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Cardioneuroablation Based on Atrial Fibrillation Nests Ablation JC PACHON-M1, Enrique I Pachon-M1, Carlos TC Pachon2, Tasso J Lobo2, Tomas G Santillana-P1, Juan C Zerpa-A2, Felipe A Ortencio2, Maria Zelia C Pachon3, Ricardo C Amarante1, Juan C Pahon-M1 (1) Sao Paulo University; (2) Sao Paulo Heart Hospital; (3) Semap Arrhythmia's Service Background: Symptomatic reflex and non-reflex functional bradyarrhythmias are related to vagal hyperactivity. Cardioneuroablation[CNA] provides vagal denervation through endocardial RF ablation of the post-ganglionic vagal neurons. Neuro-myocardium interface identification, stepwise denervation control and denervation validation are critical. Several findings have shown that the Arial Fibrillation-Nest[AFN] are intrinsically related to the vagal innervation. Objective: To verify whether CNA based on AFN ablation promotes enough vagal denervation compared to a control group with non-AFN ablation. Method: Prospective, controlled study with 54 p gathered in two groups: AFN group (AFNG-24 p) with functional or reflex bradyarrhythmias treated with AFN ablation, and a control group (CG-30 p) with anomalous bundles, ventricular premature beats, atrial flutter, nodal reentry and atrial tachycardia, treated with conventional ablation (non-AFN ablation). Ablation of AFNG was targeted to AFN detected by fragmentation of the endocardial electrograms and/or by Fractionation Software. Vagal response was evaluated before, during, and post-ablation by 5s non-contact vagal stimulation at the jugular foramen, through the internal jugular veins[ECVS], analyzing longest RR, pauses, and AV block induced by ECVS. All patients had current guidelines arrhythmia ablation indications. Results: There was found a high density of AFN over the P-Point (right half of the left interatrial septum), over the presumed areas of the main 4 ganglionated plexi, over the coronary sinus roof, and over the Waterston's groove. Pre-ablation ECVS induced sinus pauses, asystole and transient AV block in both groups, showing normal vagal response (p = 0.94). Post-ablation ECVS in the AFNG showed complete elimination of the cardiac vagal response in all cases (Pre/Post-ablation ECVS = p < 0.01), demonstrating acute and complete vagal denervation. In the CG, vagal response remained practically the same as pre-ablation (p = 0.31) showing that non-AFN ablation caused no significant denervation. Conclusion: CNA based on AFN ablation attained an excellent degree of acute vagal denervation while non-AFN ablation did not cause denervation. This fact suggests that AFNs are directly related to vagal innervation and may be a good alternative for CNA. Additionally, ECVS was remarkably valuable for CNA control. 109246 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Variables Associated with Bleeding and Thrombotic Outcomes Among Patients Admitted to the Hospital with COVID-19 and Elevated D-Dimer: Insights from the Action Randomised Clinical Trial PEDRO GABRIEL MELO DE BARROS E SILVA1, RD. Lopes4, RHM. Furtado5, AVS. Macedo1, B. Bronhara1, E. Ramacciotti6, PA. Martins7, AL. De Oliveira7, VS. Nunes7, LEF. Ritt8, AT. Rocha8, L. Tramujas2 (1) Brazilian Clinical Research Institute; (2) IP-HCor; (3) Hospital Samaritano Paulista; (4) Duke Clinical Research Institute, Durham, United States of America; (5) Hospital Israelita Albert Einstein, Sao Paulo, Brazil; (6) Loyola University, Chicago, United States of America; (7) Hospital Estadual Dr Jayme Santos Neves, Serra, Brazil; (8) Cardio Pulmonary Hospital, Salvador, Brazil In the ACTION trial, therapeutic anticoagulation did not show benefit on mortality, days of hospitalization and oxygens therapy at 30 days among patients with COVID19. However, this strategy was associated with higher rate of bleeding and a potential reduction in the rate of clinical thrombotic events. The current analysis evaluated which variables were independently associated with both outcomes in order to help the identification of the risk for thrombotic and hemorrhagic events among patients with COVID19. Methods: A total of 615 patients hospitalized with COVID-19 and elevated D-dimer were randomly assigned to prophylactic anticoagulation (mainly in-hospital heparin) or a therapeutic-dose strategy that used in-hospital rivaroxaban 20 mg/day for stable patients, or full-dose enoxaparin for unstable patients, followed by rivaroxaban through 30 days. One patient withdrew consent and was not included in the analysis. The current analysis tested baseline clinical characteristics and laboratorial exams one by one with independent logistic regressions for the composite of bleeding (major bleeding and clinically relevant nonmajor bleeding) and thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, and major adverse limb events). Significant variables (p < 0.05) were selected to adjust several multiple logistic models. Final models were chosen based on Akaike information criterion and therapeutic anticoagulation was included in the final model based on the primary results of the trial. Results: The model for bleeding events showed an accuracy of area under the curve (AUC) of 0.635 while the model for thrombotic events had an AUC of 0.725. Level of respiratory support (especially invasive ventilation) was associated with both outcomes in the multivariable analysis. Beyond respiratory support, level of creatinine and history of coronary disease were also independently associated to the risk of thrombotic events. When the utilization of therapeutic anticoagulation (mainly with rivaroxaban) was included in the multivariable analysis, this variable was strongly associated with higher risk of bleeding (model AUC of 0.718) but was not associated with lower rate of thrombotic events. Conclusion: Variables associated with higher risk of thrombotic events commonly are associated also to bleeding complications. The models developed in ACTION may help the selection of patients with better balance of risk vs. benefit to anticoagulation. 109274 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Trends in Deaths from Ischemic and Hemorrhagic Cerebrovascular Disease in Brazil from 2000 to 2019 ALESSANDRO ROCHA MILAN DE SOUZA1, Bernardo Queiroz de Carvalho Souza1, Davi da SIlveira Barroso Alves1, Glenda Borges de Lacerda1, Paulo Henrique Godoy1 (1) Universidade Federal do Estado do Rio de Janeiro - Federal University of the Rio de Janeiro State Introduction: Cerebrovascular diseases (CBVD) and cardiovascular diseases represent the leading cause of death in the world. In Brazil, these diseases correspond to 32% of deaths per year. Objective: To analyze the trend of causes of death due to ischemic CBVD (ICBVD) and hemorrhagic CBVD (HCBVD) in Brazil, from 2000 to 2019. Method: Ecological study, in which the data of deaths due to CBVD, according to ICD 10, were obtained from the Mortality Information System. The codes for CBVD were divided into: ICBVD, HCBVD and CBVD not specified as ischemic nor hemorrhagic (NSCBVD). The age groups in years were divided as 20-39, 40-59, 60-79, and 80 or above. Crude and standardized rates were estimated according to sex and age group. The variation in mortality rates was also estimated, comparing 2000 and 2019. Results: There were 1,766,788 deaths from CBVD in the period. The following distribution by causes was observed: ICBVD - 362,666; HCBVD - 409,079; NSCBVD - 1,009,927. The rates in all causes were higher in males. In the HCBVD higher death rates were observed in younger age and in the ICBVD in the older age. Stability trend was observed in the ICBVD, with a small decrease in females and a small increase in males, and a decrease trend in HCBVD and NSCBVD for both sexes. Conclusion: In general, the trend of deaths from ICBVD and HCBVD seems to be decreasing in Brazil, for the period studied, although this trend is lower in ICBVD. 109281 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Infective Endocarditis in Hemodialysis Patients CLAUDIO QUERIDO FORTES1, Natalia Rodrigues Querido Fortes3, Plinio Resende Jr4, Juliano Carvalho G. de Almeida4, Roberto Muniz Ferreira4, Ana Claudia Pinto de Figueiredo Fontes4, Luiz Felipe de Abreu Guimaraes4, Joao Roquette Fleury da Rocha4, Vlander Gomes da Costa Jr.4, Marina da Costa Carvalheira4, Ronir Raggio Luiz2, Mauro Paes Leme de Sa5 (1) Hospital Universitario Clementino Fraga Filho HUCFF/Universidade Estacio de Sa UNESA; (2) Instituto de Estudos em Saude Coletiva IESC; (3) Hospital Universitario Antonio Pedro HUAP/Hospital Universitario Clementino Fraga Filho HUCFF; (4) Hospital Universitario Clementino Fraga Filho HUCFF; (5) Hospital Universitario Clementino Fraga Filho HUCFF/Instituto do Coracao Edson Saad ICES Background: Infective endocarditis (IE) is one of the most dreaded infectious complications in hemodialysis (HD) patients. Methods: Descriptive analysis of HD and non-HD patients with IE. Results: Of the 505 patients (540 episodes) admitted to university hospital between 1978-2021 with definite IE according to the modified Duke criteria, 54 patients (57 episodes) had undergone HD and 451 (483 episodes) had not. Vascular access for HD was central catheter in 75.4% and 49,1% had arteriovenous fistula but some of them with fistula failure. The mean age of HD patients was not statistically different from that of non-HD patients (47.5 vs 43.3, p 0.117). More female gender (57.9% vs. 34.6%, p = 0.001) was observed in HD patients. Diabetes mellitus was significantly more frequent in the HD-patients (36.8% vs. 6.6%, p < 0.001), while intravenous drug use (0% vs 13.9%, p 0.029) and prosthetic valve (7.0% vs 20.7%, p 0.013) were more commonly in non-HD-patients. The mitral valve was the most affected (50.9% vs 51.1%, p 0.773), followed by aortic valve (38.6% vs 43.1%, p 0.416) and tricuspid valve (19.3% vs 13.3, p 0.212). The proportion of Enterococcus spp. was significantly higher in HD group than in non-HD group (33.3% vs. 5.4%, p < 0.001). Staphylococcus aureus was the second most frequent one (29.8% vs 22.0%, p 0.183). Valve replacement for active IE was less frequently performed among HD patients but without statistical significance (35.1% vs 42.2%, p 0.300). In-hospital mortality was significantly higher in hemodialysis than in non-hemodialysis patients (52.6% vs. 37.7%, p 0.030). Conclusions: IE is a serious complication in HD patients. Enterococcus spp. is the most common causative organism in this group. Mortality is very high and significantly higher than in non-HD patients. 109299 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Network to Control Atherothrombosis: Main Results of the Neat Registry PEDRO GABRIEL MELO DE BARROS E SILVA1, Renato Delascio Lopes4, Charlene Troiani5, Rodrigo Pinto Pedrosa6, Marcelo Nakazone7, Sergio Luiz Zimmermann8, Rodrigo Morel9, Ricardo Reinaldo Bergo10, Dalton Bertolim Precoma11, Lucas Tramujas1, Ricardo Pavanello1, Eduardo Ramacciotti12 (1) IP-Hcor; (2) Brazilian Clinical Research Institute; (3) Hospital Samaritano Paulista; (4) Duke Clinical Research Institute, Durham, United States of America; (5) Hospital Regional de Presidente Prudente; (6) PROCAPE; (7) Fundacao Faculdade Regional de Medicina Sao Jose do Rio Preto; (8) Clinica Procardio; (9) Hospital Ana Nery; (10) Hospital Santa Lucia - Hospital do Coracao de Pocos De Caldas; (11) Sociedade Hospitalar Angelina Caron; (12) Loyola University, Chicago, United States of America Background: There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. Methods: The Network to control atherothrombosis (NEAT) registry is a national prospective study of patients with known coronary (CAD) and peripheral arterial disease (PAD) in Brazil. A total of 2,015 patients were included among 21 sites from September 2020 to March 2022. The follow-up of all patients was one year by the protocol. Patient characteristics, medications under use and laboratorial data were collected. The primary objective is to assess the utilization of evidence-based therapies (EBT) at baseline. Results: From the total of patients enrolled, 56.6% had isolated CAD, 29.6% had PAD and 13.8% had both diagnoses. The overall mean age was 66.3 (+-10.5) years and 65.7% were male patients. The median glomerular filtration rate was 76.4 [57.2-96.1] and 72.3% of the patients had an evaluation of microalbuminuria which was detected in 6.2% of the cases. Regarding EBT, 4.0% were not using any antiplatelet and/or anticoagulant therapy but only 0.9% were using low dose of rivaroxaban (2.5 mg BID); 5.0% were not using statins and 55.6% of the patients were not using high intensity statin therapy; ACE inhibitors or ARBs were used in 76.2% of the overall population while, among patients with isolated CAD, 10.3% were not using betablockers. Among diabetic patients, 67.8% were using metformin and only 12.5% were using SGLT2 inhibitors and/or GLP1 agonists. Regarding the targets for secondary prevention, 33.0% had a body-mass index between 18.5 and 24.9; 44.4% were doing at least 150 minutes of exercise per week; 15.7% continued to smoke; 41.0% had a blood pressure <130 x 80 mmHg; 38.7% and 14.7% had LDL-cholesterol below 70 and 50 mg/dl, respectively. Among diabetic patients, 41.2% had a glycated haemoglobin <7%. Patients with PAD had lower use of EBT and lower percentage of patients on target of risk factors control. Among all cases without use of EBT, the main barrier identified was related to the physician perception that did not consider a formal medical indication of these therapies. Conclusion: Our findings highlight that the contemporary practice still has important gaps in the treatment of patients in secondary prevention, especially among patients with PAD. Populational interventions addressing these gaps have the potential to produce a major impact, reducing the burden of atherothrombotic complications in Brazil. 109312 Modality: E-Poster Researcher - Non-case Report Category: CARDIO-ONCOLOGY Cardioprotection Strategy Based on Positive Troponin Detection During Treatment of HER-2+ Breast Cancer FERNANDO PIVATTO JUNIOR1, Marco Aurelio Lumertz Saffi2, Guilherme Oliveira Magalhaes Costa1, Vinicius Henrique Fritsch1, Eduarda Foresti Englert1, Angela Barreto Santiago Santos2, Geris Mazzutti2, Pedro Emanuel Rubini Liedke2, Andreia Biolo1 (1) Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre-RS, Brazil; (2) Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre-RS, Brazil Introduction: Patients with positive troponin (Tn+) during breast cancer treatment are considered to be at high risk for cardiotoxicity, and cardioprotection with ACE+-BB is indicated. Doubts persist about the ideal time to collect Tn. Objective: To compare the incidence of cancer therapy-related cardiac dysfunction (CTRD) in the Tn+/onset of cardioprotection and Tn-/no additional intervention groups. Patients and methods. Prospective cohort including consecutive female patients with HER-2+ early breast cancer who consulted at the institution's breast cancer outpatient clinic between march/19-march/22. CTRD: drop in LVEF > 10 p.p. to <53% (ASE/EACI). Tn collection was performed together with the lab tests requested by Oncology before the 1st and 2nd cycles of trastuzumab (TTZ), in addition to 3 months after its initiation. Tn+: TnTus >= 14 ng/L or TnIus > 15.6 pg/mL. It was not considered as Tn+ if baseline Tn+ without previous cancer treatment or if absence of increase >20% after its beginning. Patients with Tn+ were referred to the institution's Cardio-Oncology outpatient clinic to begin cardioprotection, as were those with CTRD. Comparison between groups: Fisher's exact test. P < 0.05 was considered statistically significant. Results: We studied 46 patients, mean age 53.1 +- 13.1 years, 21 (45.7%) in a therapeutic protocol including doxorubicin (ACdd-TH). Regarding risk factors, 21 (45.7%) had a history of smoking, 18 (39.1%) were obese and 15 (32.6%) had hypertension. Of the 138 troponins analyzed, there were 18 (13.0%) Tn+, the majority being detected before the 2nd cycle of TTZ (12/18, 66.7%). Of the total number of patients, 12 (26.1%) had >=1 Tn+, with the majority (7/12, 58.3%) having only one of the three collected. In the (n = 34), only 6 (17.6%) had hypertension and used ACEi/ARB as treatment. The incidence of CTRD was 10.9%, 8.3% in the Tn+ group and 11.8% in the (P = 1.0). Conclusions: Although patients with Tn+ had a higher risk of CTRD, there was no difference in the incidence in those with Tn+/onset of cardioprotection in relation to those with Tn-/without additional intervention. This finding suggests that the cardioprotection strategy based on the detection of Tn+ collected together with the lab tests requested by Oncology may have been effective, equating the occurrence of this adverse event between the groups. 109383 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Association between the Number of Cardiovascular Risk Factors and Coronary Calcification PAULO EDUARDO BALLVE BEHR1, Rafael Vianna Behr1, Leonardo Henrique Bertolucci1, Gabrielly Burkhard Vilasfam1, Lara Helena Zortea1, Luiza Zwan Dutra1, Maiara Both1, Mariana Saadi de Azevedo1, Paulo Ernesto Leaes1, Fernando Antonio Lucchese1 (1) Hospital Sao Francisco - Santa Casa de Misericordia de Porto Alegre Introduction: Traditional risk factors (RF) are used to predict the probability of cardiovascular events. However, it is still uncertain whether they are able to predict the probability of subclinical atherosclerosis. Therefore, our objective is to evaluate the association between the number of RF and coronary calcification measured by the calcium score (CAC). Methods: Cross-sectional study, including patients seen as outpatients between 2012 and 2020, aged between 45 and 75 years, in primary prevention. To assess coronary calcification, the CAC percentile (PCAC) was used, considering PCAC > 75 as an important calcification. The RF evaluated were: hypertension, diabetes, current smoking, dyslipidemia and family history (FH) for coronary artery disease. Results: 444 patients were included, mean age 59 +- 7 years, 54% female, all Caucasian, 54% hypertensive, 41% dyslipidemic, 9% diabetic, 11% smokers; 59% with FH. Table 1 shows the association between the number of RF and coronary calcification. The higher the number of RF, the higher the prevalence of PCAC > 75 (p < 0.01) and the lower the prevalence of PCAC = 0 (p < 0.01). Compared to patients without RF, the prevalence of PCAC > 75 was 1.86 times higher in patients with 1 risk factor (CI 0.60-5.81), 3.59 times higher with 2 RF (CI 1.20-10.76), 3.89 times higher with 3 or more RF (CI 1.27-11.90). However, even in patients with zero, 1, or 2 RF, significant calcification was observed in 9.1%, 16.9%, and 32.6% of patients, respectively. In multivariate analysis, smoking [PR 1.68 (CI 1.16-2.43)] and FH [PR 1.96 (CI 1.37-2.79)] were independent RF. Conclusion: There was an association between the number of RF and coronary calcification. However, a considerable percentage of patients with none or fewer RF had significant coronary calcification. 109364 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Distal Transradial Access for Post-Cabg Coronary and Surgical Grafts Angiography and Interventions MARCOS DANILLO PEIXOTO OLIVEIRA1, Lelio Lemos Pinto Neto1, Ednelson Navarro2, Adriano Caixeta1 (1) Universidade Federal de Sao Paulo, UNIFESP; (2) Hospital Regional do Vale do Praiba Background: Post-CABG coronary and grafts angiography (CGAG) and interventions (PCI) have historically been performed via classic transfemoral approach. Particularly for those with left internal mammary artery (LIMA) grafts, left standard transradial access (lsTRA) represents a feasible alternative, with significant fewer vascular complications, but it has ergonomic disadvantage for the operator because of the need to bend over the patients, especially in obese ones. Distal transradial access (dTRA) may provide important advantages, including shorter hemostasis and greater patient and operator comfort, mainly for left dTRA (ldTRA). We aim to describe the feasibility and safety of right and left dTRA for post-CABG CGAG and PCI. Material and methods: From February 2019 to February 2022, 151 consecutive post-CABG patients submitted to CGAG and/or PCI via dTRA have been enrolled. Results: Mean patient age was 67.81 years old. Most were male (82.1%) and had chronic coronary syndromes (59.6%). Overall, 40.3% had acute coronary syndromes. Distal RA was successfully punctured in all patients, always without ultrasound guidance. All procedures involving LIMA grafts were done via ipsilateral ldTRA. We had only 9 (6.0%) access site crossovers. Successful dTRA sheath insertion was then achieved in 94% of all patients, mostly (66.9%) via ldTRA and with standard 6Fr sheath (98%). Distal and proximal RA pulses were palpable in all patients at hospital discharge. No major adverse cardiac and cerebrovascular events and no major complications related to dTRA were recorded. Conclusions: dTRA for routine post-CABG CGAG and PCI by experienced transradial operators appears to be feasible. Further randomized and larger trials are needed to assure clinical benefits and safety of this new technique. 109367 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Correlation between Nonalcoholic Fatty Liver Disease and the Severity of Acute Coronary Syndrome: A Retrospective Study MARIO CLAUDIO SOARES STURZENEKERM1, Mauricio Montemezzo2, Dalton Bertolim Precoma2, Paola Goncalves Moreira de Oliveira1, Bruna Karas1, Ana Carla Dlugosz1, Alice Magro Koscianski1, Larissa Almeida Busnello1, Francielle Nocera Viechineski1, Camilla Mattia Calixto1, Julia Henneberg Hessman1 (1) Universidade Estadual de Ponta Grossa; (2) Pontificia Universidade Catolica do Parana Introduction: Cross-sectional studies have widely described the relationship between non-alcoholic fatty liver disease (NAFLD) and atherosclerotic coronary artery disease. A clinical study reported an increased risk for cardiovascular events in NAFLD patients, and this relation was suggested in a retrospective study. However, the role of NAFLD in atherosclerotic disease remains inadequately elucidated. Furthermore, the potential correlation between NAFLD severity and the clinical expression of acute coronary syndrome (ACS) remains undetermined. Purpose: To assess whether there is a correlation between NAFLD severity and ACS severity. Methods: Were selected data of 99 adult patients without previously known coronary artery disease or liver disease, without a history of significant alcohol consumption and other common causes of secondary steatosis, who presented to the emergency room with chest pain between March 2015 and March 2016. The diagnostic criteria for acute myocardial infarction with ST-segment elevation (STEMI) were based on ST-elevation >=1 mm in >=2 contiguous leads (2 mm for leads V1 to V3). The acute myocardial infarction without ST-segment elevation (NSTEMI) diagnostic was established in patients who did not meet the criteria for STEMI and who had elevated necrosis markers (creatine kinase-MB isoform and troponin I). Unstable angina (UA) diagnostic was established in patients who did not meet the criteria for STEMI and NSTEMI but had more than three cardiovascular risk factors and typical thoracic pain. The presence of steatosis and its degrees were assessed using ultrasound, and the diagnosis of NAFLD was based on the presence of steatosis and clinical history. Results: UA, NSTEMI and STEMI diagnosis were established in 40, 33 and 26 patients, respectively, and NAFLD was observed in 30%, 66.6% and 76.9% of these patients. The diagnostic of STEMI and NSTEMI were more frequently than UA in NAFLD patients (P < 0.01, p < 0.001). NAFLD diagnosis and its degrees were significantly correlated with the three presentations of ACS (P < 0,001) for both. The STEMI and NSTEMI diagnosis frequency was similar in NAFLD patients. Diabetes, obesity and hypertension were not correlated with NAFLD diagnosis and degree. Conclusion(s): In this study, NAFLD diagnosis and its degrees were significantly correlated with ACS and its severity. Therefore, NAFLD could be considered a potential risk marker for coronary atherosclerotic disease progression and instability. 109382 Modality: E-Poster Researcher - Non-case Report Category: NURSING Value-Based Chronic Care Model Approach for Patients with Arterial Hypertension and Diabetes Mellitus in Brazil: A Cross-Sectional Study DALMA ALVES PEREIRA1, Priscila Valverde de Oliveira Vitorino2, Katarinne Lima Moraes3, Vanessa da Silva Carvalho Vila2, Marina Aleixo Diniz Rezende2, Maria Alves Barbosa1, Claudia Regina de Oliveira Zanini1, Virginia Visconde Brasil1 (1) Federal University of Goias - UFG; (2) Pontifical Catholic University of Goias - PUC Goias; (3) Brasilia University - UnB Background: Support for self-management of chronic conditions is essential in the development of patient-centered care. The use of integrated care models that focus on the person and not only on the disease represents a viable solution for effective care. The Chronic Care Model is based on the relationship between motivated and informed users, and a proactive and prepared health team. According to this model, support for self-management is associated with significant results, especially in hypertension and diabetes. It includes the Patient Assessment of Care for Chronic Conditions (PACIC) instrument to assess and monitor the integrated care and support for self-management, as perceived by the patient. Aim: To assess the quality of care for people with arterial hypertension and diabetes mellitus treated at a specialized service, according to the Chronic Care Model. Methods: Cross-sectional study, carried out in a reference outpatient clinic of hypertension care in Brazil. Eighty-two people with diabetes and hypertension were evaluated, with a follow-up of at least 5 years. Participants completed the 20-item PACIC, as well as measures of demographic and clinical aspects during the nursing appointment. PACIC has 5 scales and 3 of them assess support for self-management. Higher scores (>3.0) indicate greater involvement in self-management and team support. For analysis, the Mann-Whitney Test, Spearman Test, and a significance level of 0.05 were used. Results: The mean age was 68.98 +- 8.79 years, female (82.93%), and median 4 years of study (IQR 3-8). Most parents (70.73%) did not study. The median time from diagnosis of diabetes was 8 years (IQR 6-12). Less than half of the patients had controlled glycated hemoglobin - HbA1c (34.15%) and blood pressure (36.59%). There was a positive correlation between the time of diabetes diagnosis and the (HbA1c) value. The Overall PACIC mean was 3.4 (IQR 2.8-3.8). The scales scores that map onto self-management support were Patient Activation - 3.0; Problem-Solving/Contextual - 3.0 and Goal Setting/Tailoring - 3.8. Patients with controlled (HbA1c) were significantly different on the Goal Setting/Tailoring scale. Having parents with some schooling was significantly different on both the Overall PACIC and Patient Activation scale. Conclusion: Quality of care was high considering the overall PACIC, but was moderate on scales that assess greater patient participation and involvement in decision-making and treatment plans. 111107 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Cost-Effectiveness Analysis of Pare de Fumar Conosco: An Electronic Decision-Making Tool for Quitting Smoke ROBERTA DA SILVA TEIXEIRA1, Arise Garcia de Siqueira Galil2, Ana Paula Cupertino3, Francisco Cartujano-Barrera3, Fernando Antonio Basile Colugnati2 (1) Instituto Nacional de Cardiologia - INC; (2) Universidade Federal de Juiz de Fora - UFJF; (3) University of Rochester Medical Center - URMC Introduction: E-health technologies such as the Pare de Fumar Conosco software can be effective for smoking treatment. This intervention is a web-based tool for decision-making about quitting smoking, drawn on principles of social cognitive theory, comprising motivational messages, behavioral change support, and pharmacotherapy use. Efficacy and effectiveness evaluations are not enough. Before being adopted in the health system, technologies must be adequately evaluated in the economic sphere. Objective: To evaluate the cost-effectiveness of the Pare de Fumar Conosco software versus the standard of care according to Brazilian Ministry of Health guidelines. Methods: We developed an analytical decision model for engagement in the smoking cessation counseling group and smoking cessation under service providers' perspectives and the public health system. We measured costs by primary and secondary sources and a randomized clinical trial for effectiveness. The temporal horizon adopted was one year. The TreeAge Pro Suite 2018 software guided the development of the analytical decision model. The analysis comprised the incremental cost-effectiveness ratio (ICER), deterministic sensitivity analysis, and Monte Carlo probabilistic analysis (1,000 simulations). As the outcomes are intermediary, no willingness to pay threshold was adopted. Results: The software had a lower cost and greater effectiveness than its comparator. ICER for the engagement and smoking cessation were dominant in both perspectives adopted ($ - 464, 125.36 to $ - 58,348.50). Quadrant II (lower cost and higher effectiveness) presented higher percentages (53,6% to 82,5%) on Monte Carlo simulations. Conclusions: Pare de Fumar Conosco software is a cost-saving technology for smoking treatment. This cost-effectiveness analysis provides objective and explicit data that support the decision of health managers in evaluating the adoption of a promising web-based decision tool for smoking cessation. 109401 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Results of Comprehensive Rehabilitation Program of Patients After Left Ventricular Assist Device Implantation TOMASZ CHWYCZKO1, Edyta Smolis-Bak1, Laura Zalucka1, Agnieszka Segiet-Swiecicka1, Ewa Piotrowicz1, Joanna Was1, Magdalena Niedolistek1, Malgorzata Sobieszczanska-Malek1, Tomasz Zielinski1, Mariusz Kusmierczyk1, Ryszard Piotrowicz1, Rafal Dabrowski1 (1) National Institute of Cardiology, Warsaw, Poland Background: The novel method of comprehensive rehabilitation after LVAD implantation was developed in our institution in order to rehabilitate the growing LVAD patients population. Study group: 47 recent LVAD (32 HeartMate III, 15 HeartWare) recipients (19-68 years, mean 58,7 years, 43 men) participated in the rehabilitation program. 4-5 week program included supervised endurance training on a cycle ergometer (5 times per week). The training was programmed on the basis of the cardiopulmonary exercise test results. Other exercises included: resistance training, general fitness exercises with elements of equivalent and coordination exercises (every day). The hospitalization was followed by 6-8 weeks of individual exercises performed at home. 6-minute walking test (6MWT), cardiopulmonary exercise test (CPET) and prognostic biomarkers of heart failure: NT-proBNP, Galectin-3 and ST2 were investigated at the beginning and at the end of the rehabilitation program. Results: Table 1. An increase of 6MWT distance, higher maximal workload, peak VO2 and upward shift of anaerobic threshold in CPET were observed in all patients. Significant reductions of NTproBNP, ST2 and galectin-3 levels were observed. There were no major adverse events during rehabilitation. Conclusions: Comprehensive novel rehabilitation in LVAD recipients is safe and results in significant improvement of functional tests and biomarkers of heart failure. 109413 Modality: E-Poster Researcher - Non-case Report Category: NUTRITION Evaluation of Red Wine Influences on the Gut Microbiota and Trimethylamine N-Oxide ELISA ALBERTON HAAS1, Mario Jose Abdalla Saad2, Andrey Santos2, Nicola Vitulo3, Wilson Jose Fernandes Lemos Junior4, Aline Maria Araujo Martins5, Carolina Raissa Costa Picossi6, Desiderio Favarato1, Renato Simoes Gaspar1, Peter Libby7, Francisco Rafael Martins Laurindo1, Protasio Lemos da Luz1 (1) Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; (2) Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas, SP, Brazil; (3) Department of Biotechnology, Verona University, Verona, Italy; (4) Faculty of Science and Technology, Libera Universita di Bolzano, Bolzano, Italy; (5) Department of Medical Science, University of Brasilia (UnB), Brasilia, Brazil; (6) Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil; (7) Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Gut microbiota profile closely relates to cardiovascular diseases through mechanisms including the reported deleterious effects of metabolites, such as trimethylamine-N-oxide (TMAO), highly studied as a diagnostic and therapeutic target. Moderate red wine (RW) consumption is reportedly cardioprotective, but RW effects on gut microbiota and plasma TMAO are not fully understood. We conducted a randomized, crossover, controlled trial involving 42 males, average 60 yr with documented coronary artery disease, comparing 3-week consumption of 250 mL of RW/day, 5 days/week, with an equal period of alcohol abstinence, given adequate washouts. RW consumption significantly remodeled gut microbiota, with a difference in beta diversity. Plasma metabolomic analysis (n = 20) revealed changes after RW consistent with improved redox homeostasis modulation, such as an increase in precursors of riboflavin and ascorbate metabolism. In contrast, plasma TMAO did not differ with the RW intervention and TMAO levels showed a low intra-individual concordance over time. Thus, modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. 109418 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Deep Learning and High-Performance Computing for Screening Patients with Depression in Primary Care ERITO MARQUES DE SOUZA FILHO1, Erito Marques de Souza Filho1, Helena Cramer Veiga Rey2, Rose Frajtag2, Daniela Matos Arrowsmith Cook3, Lucas Nunes Dalbonio de Carvalho1, Antonio Luiz Pinho Ribeiro4, Samuel Santana de Oliveira5, Filipe Silva Neves Nogueira dos Santos5, Jorge Amaral6 (1) Universidade Federal Rural do Rio de Janeiro; (2) Instituto Nacional de Cardiologia; (3) Pro-Cardiaco; (4) Universidade Federal de Minas Gerais; (5) Senai Cimatec; (6) Universidade do Estado do Rio de Janeiro Cardiovascular disease and depression are prevalent. Patients with cardiovascular disease are more depressed than the normal population. Depression is associated with an increased risk of cardiovascular disease (CVD) and death. People with CVD who are also depressed fare worse than patients who are not depressed. Depression's intensity influences one's risk of death and other cardiovascular problems. Depression is a multifactorial disease that has a high socio-economic impact. Currently, many patients do not receive adequate treatment or diagnosis. In this context, the present work proposes a Deep Learning model for diagnostic screening of patients in primary care using clinical, laboratory, and sociodemographic data. These data were obtained from a telecardiology project of the Cardiovascular Disease Research Network from 2016 to 2018. Due to the complexity and processing demand, we used a high-performance supercomputer (OGBON - Senai/Cimatec) in the hyperparameter search process, training, and testing the models. We utilized a cross-validation strategy to aim at a better evaluation of the external validation of the model. We designed SMOTE and TOMEK links for data augmentation. We implemented the models in Python and used the Optuna package in searching best parameters. We used the area under the receiver operating characteristic curve, recall, precision, F1-score, and accuracy in models evaluation. Our best model reached, respectively, 0.81, 0.76, 0.88, 0.81, and 0.76. These results indicate that Deep Learning has great potential in terms of screening patients with depression based on data from routine use in primary care. 109428 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Smoking Cessation is Associated with Short-Term Improvement in Vascular Health in a Cohort of People Living with HIV/AIDS in Rio de Janeiro RODRIGO DE CARVALHO MOREIRA1, Anny Rodrigues22, Beatriz Leonardo1, Daniel Arabe1, Sandra Wagner1, Beatriz Grinsztejn1, Valdilea Veloso1, Antonio Pacheco3 (1) Evandro Chagas National Institute of Infectious Diseases; (2) Universidade Federal do Rio de Janeiro; (3) Programa de Computacao Cientifica, Oswaldo Cruz Foundation Background: Smoking is highly prevalent in people living with HIV/AIDS (PLHA) producing detrimental effects in different organs and leading to illness. There is limited evidence about pharmacological interventions for treating nicotine dependence in PLHA. We examined if Nicotine replacement therapy (NRT) is an option for smoking cessation and ameliorates vascular health in this specific population. Methods: From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking in our center. The primary outcome of interest was to assess the effect of NRT plus counseling on smoking cessation and endothelial function measured by brachial artery flow-mediated dilatation (FMD). Statistical analysis evaluated the change in %FMD (D%FMD = %FMD at week12-%FMD at baseline) to test the hypothesis that D%FMD would improve among participants who quit smoking compared to those who relapse. To confirm the results, we have run multiple linear regression to account for classical cardiovascular (CV) confounders. Results are presented in medians (interquartile ranges) and percentages. Results: We included 115 participants with median age of 45.5 years (IQR = 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes and 30 (27.8%) had dyslipidemia, almost half were smoking 20+ cigarettes/day (41.7%). Individuals were living with HIV for a median of 10.9 years (5.7-17.4) and were on antiretroviral therapy for 8.6 years (3.7-13.6) with median Nadir of CD4 of 307 (153-490.5). Baseline of median brachial artery diameter was 3.6 mm (IQR = 3.2-4.1). Unadjusted analysis showed that years of smoking, younger age and white race were associated with poor %FMD (75th per centile). After 12 weeks 29.6% participants quit smoking. Comparison of D%FMF showed that among participants adherent to therapy, there has been an increase in D%FMD when compared to those who relapsed (1.11% [0.29-2.93] vs -0.15% [-1.8-0.91], p < 0.001). After adjustment for CV factors, multiple linear regression showed that participants who quit smoking present a mean 2.53 (p = 0.007) points increase in D%FMD in comparison to those who continued to smoke. Conclusion: This study provides evidence that a strategy of NRT and counseling is effective for smoking cessation in PLHA and improves their vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering incidence of future cardiovascular events. 109452 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Iron Supplementation in LVAD Patients with Iron Deficiency and Anemia - Comparison of Treatment Strategies TOMASZ CHWYCZKO1, Laura Zalucka1, Agnieszka Segiet-Swiecicka1, Edyta Smolis-Bak1, Ilona Kowalik1, Malgorzata Sobieszczanska-Malek1, Tomasz Zielinski1, Anna Borowiec1, Mariusz Kusmierczyk1, Rafal Dabrowski1, Ryszard Piotrowicz1 (1) National Institute of Cardiology, Warsaw, Poland; (2) National Institute of Oncology, Warsaw, Poland Background: Iron Deficiency (ID, ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) is present in up to 70% of LVAD (left ventricular assist device) recipients. It causes severe anemia, impairs exercise tolerance, and may worsen the prognosis. Aim of the Study: To determine, which method of iron supplementation: oral or intravenous, is more efficient in LVAD patients. Methods: In 47 recent LVAD recipients (19-68 years, median age 58.7 yrs, 43 men) iron parameters were investigated. 35 patients (74.5%) were diagnosed with ID and 44 patients (93.6%) had anemia. 27 patients were treated with intravenous iron (ferric carboxymaltose, average dose 1248 mg), 9 pts were treated with oral iron, 11 pts did not receive iron (high ferritin level). Blood morphology and iron management markers: serum iron level, transferrin, ferritin, transferrin saturation - TSAT, were measured before and 3 months after the therapy. Results: Resolution of ID was observed in 19 pts from IV Iron Group (73.1%), and in one patient from Oral Iron Group (12.5%), p = 0.002. 8 pts from no treatment group developed ID. Intravenous repletion was more efficient than oral supplementation in ID resolution: OR = 16.29, 95% CI = 2.25-338.1, p = 0.017. IV treatment was more effective than no treatment strategy in anemia resolution: OR = 18, 95% CI = 3.03-159.4, p = 0.003. Conclusions: The study proves the advantage of intravenous over oral iron treatment in LVAD patients. 109460 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Association between Family History for Coronary Disease and Coronary Calcium Score PAULO EDUARDO BALLVE BEHR1, Rafael Vianna Behr1, Leonardo Henrique Bertolucci1, Gabrielly Burkhard Vilasfam1, Lara Helena Zortea1, Luiza Zwan Dutra1, Maiara Both1, Mariana Saadi de Azevedo1, Paulo Ernesto Leaes1, Fernando Antonio Lucchese1 (1) Hospital Sao Francisco - Santa Casa de Misericordia de Porto Alegre Introduction: It is still uncertain how the family history (FH) for coronary heart disease (CAD) should be assessed: at any age or through the inclusion of an age cutoff. In this work, we evaluated the association between FH at any age and coronary calcium score (CAC). Additionally, we analyzed the influence of the number of family members on the probability of having significant subclinical atherosclerosis. Methods: Cross-sectional study, including patients seen as outpatients between 2012 and 2020, aged between 45 and 84 years, in primary prevention. For FH, parents or siblings were considered, with sudden death, AMI, coronary angioplasty or CABG, at any age. To assess coronary calcification, the CAC percentile (PCAC) was used, with PCAC > 75 being considered important calcification. Results: 509 patients were included, mean age 60 +- 8 years, 54% female, all Caucasian, 55% hypertensive, 36% dyslipidemic, 11% diabetic, 11% smokers; 58% with HF for CAD. The table shows the distribution of PCAC according to FH. Compared to patients without FH, the prevalence of PCAC > 75 was 1.65 times higher in patients with FH (CI 1.20-2.26); 1.59 times higher with a family member with CAD (CI 1.14-2.22); 1.58 times higher with two family members (CI 1.00-2.48); and 2.52 times higher with three or more family members (CI 1.51-4.23). The prevalence of PCAC > 75 with 1 or 2 family members was 31%, while with 3 family members it was 50% (p = 0.053). In addition, the greater the number of family members, the greater the prevalence of PCAC > 0 (p = 0.002). Conclusion: In this study, the presence of FH for CAD was associated with a higher prevalence of significative coronary calcification. In addition, the greater the number of family members, the greater the chance of coronary calcification. 109873 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Initial Experience with Left Atrial Appendage Occlusion using the AmplatzerTM and the WatchmanTM Dedicated Devices, in a Single Center from Brazil SERGIO GUSTAVO TARBINE1, Costantino R Costantini1, Costantino Ortiz Costantini1, Shibata Vinicius1, Marcos Denk1, Rafael Macedo1, Marcio M. Luize1, Everton Cardoso Dombek1 (1) Hospital CArdiologico Costantini Background: The AmplatzerTM and the WatchmanTM are dedicated devices for percutaneous left atrial appendage (LAA) occlusion. This is an elective procedure planned to avoid thrombus-embolizaton in patients with atrial fibrillation, unable to use anticoagulation. Objectives: The aim of the study was to describe the initial experience with both devices for percutaneous LAA occlusion. Methods: This is a single-center study of patients undergoing percutaneous LAA occlusion. Inclusion criteria considered a formal contraindication for oral anticoagulation, previous history of stroke due to INR lability, left atrial thrombus in use of NOACs, and patient preference. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed during the first 24hs after the procedure in order to rule out complications. Further follow-up was done with clinical visits and TEE. Results: Between 09-2010 and 10-2021, patients with a mean CHA2DS2-VASC of 4.6 +- 0.8 and Has-bled of 4,5 underwent LAA occlusion with the AmplatzerTM device (24) and the WatchmanTM device (8). Both were successfully implanted in 32 patients (100%), 75,1 +- 2,7 yrs old, 75% male, without any procedural stroke or device embolization. TEE showed complete LAA sealing in all patients with no residual leaks. Pericardial effusion needing successful pericardiocentesis in 3 patients. During follow-up, 1 patient had minor retinal embolization and 3 patients died (1: cancer; 2: not related osteomyelitis; 3: chronic renal failure.). Conclusion: In this initial series of patients, both devices showed a good acute and short-term performance considering feasibility and safety regarding the successful implantation rate and the low incidence of complications. 109495 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Effects of Weight Loss on Lipid Transfer to HDL in Grade III Obese Individuals After 1 Year of Bariatric Surgery WILSON PASCOALINO CAMARGO DE OLIVEIRA1, Fatima Rodrigues Freitas2, Mauricio Tavares Costa2, Aline de Oliveira Silva2, Roberto Kalil Filho2, Marco Aurelio Santo3, Raul Cavalcante Maranhao2 (1) Department of Clinical Analysis - FCF-USP; (2) Laboratory of Metabolism and Lipids - InCor; (3) Department of Clinical Analysis - FCF-USP/Discipline of Surgery of the Digestive System at HCFMUSP Introduction: Obesity leads to decrease in HDL-C, which is an independent risk factor for cardiovascular events. Bariatric surgery is an effective treatment for grade III obesity, which leads to decreased LDL-C, triglycerides and increases HDL-C. The impact of bariatric surgery on anti-atherosclerotic functions of HDL, such as transfer of cholesterol from other lipoproteins to HDL was not yet explored. Aim: To evaluate the effects of weight loss by bariatric surgery on the transfer of lipids to HDL and plasma lipids and apolipoproteins (apo) 1 year after bariatric surgery. Methods: Fifteen individuals with grade III obesity (43 +- 6 years, BMI 49 +- 3 kg/m2, 14 women) were evaluated before and 1 year after bariatric surgery. Blood samples were obtained after a 12-hour fast. Lipid transfer to HDL was measured by in vitro assay, using an artificial emulsion labeled with 3H-cholesteryl ester and 14C-cholesterol as lipid donor. Lipids, apo A-I, apo B, glucose, insulin, and C-reactive protein (CRP) were determined by commercial kits. Insulin resistance was estimated by HOMA-IR index. HDL diameter was measured by laser light scattering method. Results: As expected, BMI decreased after surgery (49 +- 6 vs 35 +- 5 kg/m2; p < 0.0001). Total cholesterol (174 +- 43 vs 154 +- 25 mg/dL; p = 0.022), LDL-C (105 +- 34 vs 78 +- 19 mg/dL; p = 0.007), non-HDL-C (128 +- 39 vs 91 +- 19 mg/dL; p < 0.0001), triglycerides (113 +- 39 vs 72 +- 19 mg/dL; p = 0.0012) and apo B (105 +- 27 vs 78 +- 13 mg/dL; p < 0.001) decreased after surgery. On the other hand, HDL-C (46 +- 9 vs 62 +- 10 mg/dL; p < 0.0001), apo A-I (136 +- 24 vs 157 +- 25 mg/dL; p < 0.0029) and diameter of the HDL (8.88 +- 0.39 vs 9.12 +- 0.34 nm; p < 0.05) were increased. CRP (9.77 +- 6.23 vs 1.75 +- 1.90 mg/dL; p < 0.0001) and HOMA-IR index (10.4 +- 12.2 vs 2.07 +- 0.97; p < 0.05) decreased compared to pre-surgical values. Transfer of unesterified (3.64 +- 0.86 vs 3.79 +- 1.05%) and esterified cholesterol (3.42 +- 0.48 vs 3.20 +- 0.52%) to HDL were not changed after surgery. Conclusions: The weight loss 1 year of after bariatric surgery improved plasma lipids, including HDL-C and promoted reduction of insulin resistance and systemic inflammation associated to grade III obesity, and all those changes conceivably contribute to the diminished cardiovascular risk reported in the literature. However, the surgery did not impact the transfer to HDL of both cholesterol forms, which is also involved in atherogenesis. 109526 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Intermittent Aortic Cross-Clamping with Hypothermia in Coronary Artery Bypass Grafting Surgery: Troponin Evaluation and Outcomes ASSAD MIGUEL SASSINE1, Jose Carone Filho1, Elisa ito mendes de Andrade1, Ramon Ott Vargas1, Jose Silva Henrique1, Marcio Luiz Roldi1, Lucio Pereira Guarconi1, Dalton Vinicius Menin1, Carlos Alberto Sancio Junior1, Ana Carolina Simoes Ramos1, Jose Carone Junior1, Schariff Moyses2 (1) Hospital Evangelico de Vila Vleha; (2) Instituto de Cardiologia Do Espirito Santo Introduction: Coronary artery bypass grafting (CABG) surgery is an important weapon in the therapeutic arsenal of coronary artery disease. The aim is to perform a safe procedure, with myocardial preservation and a low rate of perioperative complications. The purpose of this study is to evaluate myocardial injury and clinical evolution in patients undergoing CABG in a referral hospital in Espirito Santo state, where intermittent aortic clamping in hypothermia is used as a myocardial protection strategy. Methods: Observational, cross-sectional and prospective study were developed in a referral Hospital in Espirito Santo state. Results: 108 patients were included in the study between April and December 2019. The mean age of patients was 65 years. The mean EuroSCORE II was 2.54 and the mean Society of Thoracic Surgeons (STS) score was 1.54. Most patients were male (62%) and 75.9% had hypertension. Approximately half of patients had diabetes mellitus and dyslipidemia. Less than a fifth of the sample reported prior acute myocardial infarction. Mean cardiopulmonary bypass (CPB) time was 56 minutes and the average period of cross-clamping time was 43 minutes. Cardiac troponin I alterations were associated with death when considered from 6.1 ng/mL on the 1st postoperative day; values >6.1 ng/mL were related to longer CPB and times. Conclusion: The technique of intermittent aortic cross-clamping in CABG surgery proved to be safe, with a low rate of postoperative morbidity and mortality. New studies, including analyzes with a larger sample, should be carried out to better understand this relationship. 109552 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Is the Acc/Aha Risk Score Able to Predict Coronary Calcification? PAULO EDUARDO BALLVE BEHR1, Rafael Vianna Behr1, Leonardo Henrique Bertolucci1, Gabrielly Burkhard Vilasfam1, Lara Helena Zortea1, Luiza Zwan Dutra1, Maiara Both1, Mariana Saadi de Azevedo1, Paulo Ernesto Leaes1, Fernando Antonio Lucchese1 (1) Hospital Sao Francisco - Santa Casa de Misericordia de Porto Alegre Introduction: The ACC/AHA 10-year Atherosclerotic Cardiovascular Disease Risk Score (ACC/AHA Score) is one of the most used to assess the risk of MI or stroke. However, it was not evaluated whether it is able to identify individuals with greater or lesser coronary calcification. Therefore, our objective is to assess whether the risk categories of the ACC/AHA Score are able to predict coronary calcification. Methods: Cross-sectional study, including patients seen as outpatients between 2012 and 2020, aged between 41 and 69 years, in primary prevention. Patients were divided into the four risk categories of the ACC/AHA Score: low (<5%), borderline (>=5% and <7.5%), intermediate (>=7.5% and <20%) and high (>=20%). Coronary calcification was measured by the Calcium Score (CAC), using absolute values (in Agatston), and CAC >= 100 was considered a significative calcification. Results: 518 patients were included, mean age 59 +- 8 years, 52% female, all Caucasian, 54% hypertensive, 59% dyslipidemic, 11% diabetic, 11% smokers. The Table shows the distribution of CAC according to the ACC/AHA risk category. The increase in risk category was associated with a progressively higher prevalence of CAC >= 100 (p < 0.01), just as the reduction of category was associated with a higher prevalence of CAC = 0 (p < 0.01). Compared to low-risk patients, the prevalence ratio for CAC >= 100 was 2.35 in borderline-risk patients [(CI 1.44-3.82) (p = 0.01)]; 2.88 in intermediate risk [(CI 1.89-4.39) (p < 0.01)] and 4.32 in high risk [(CI 2.73-6.82) (p < 0. 01)]. Conclusion: In a population sample from southern Brazil, we observed that the ACC/AHA Score categories are able to predict the probability of significant subclinical atherosclerosis, assessed by coronary calcification. 109571 Modality: E-Poster Researcher - Non-case Report Category: NURSING Development of Nursing Technology for the Management of Tachycardias in Intensive Care: Experience Report ERICA SOBRAL GONDIM1, Emiliana Bezerra Gomes1, Jose Hiago Feitosa de Matos1, Ana Camila Goncalves Leonel1, Sarah de Lima Pinto1, Amanda da Costa Sousa1, Antonia Elizangela Alves Moreira1, Raynara Augustin Queiroz1, Ana Luiza Rodrigues Santos1, Mariane Ribeiro Lopes1 (1) Universidade Regional do Cariri - URCA Introduction: Critical care units are characterized by the continuous monitoring of physiological parameters essential to the maintenance of life and the immediate conduct of health interventions. Subtle changes in organic functioning variables are indicative of potential risks to homeostasis, which can cause events that culminate in interruption of blood flow to vital organs and cardiorespiratory arrest. Heart rate, the number of beats per minute that determines the effectiveness of blood pumping from the heart to the other organs, is one of the vital parameters in controlling the proper functioning of the cardiovascular system. Although it may indicate a cardiac disorder itself, tachycardia is also present in non-cardiac conditions common in the Intensive Care Unit (ICU), such as delirium, shock, sepsis, anxiety, pain, inadequate management of sedation and respiratory distress. In this context, a nursing guide was developed to approach tachycardias in the ICU, seeking to optimize the time to restore hemodynamic balance and prevent cardiorespiratory arrest. Objective: The present study, therefore, aims to report the experience of an intensive care nurse in the development of an instrument that classifies tachycardias according to intervention priorities and action packages. Method: This is an experience report on the development of nursing technology by the professional, whose 12-year experience in intensive care and immersion in studies on the subject provided subsidies to identify priorities and conduct them properly according to their own professional skills. Results: The elaborate script identified cardiac and non-cardiac causes, directing a direct nursing intervention to each cause and its time of completion according to the required urgency, citing in each intervention the subsequent steps and the professionals who must be activated according to the limits of professional exercise. Conclusions: The development of this technology, based on the technical competence and experience of the professional nurse, followed an approach, although simple, practical and directed to the most prevalent causes in the ICU. The instrument resulting from this perception demonstrates practicality and applicability in routine care and nursing in the prevention of adverse events in intensive care units, optimizing the quality of care provided. 109608 Modality: E-Poster Researcher - Non-case Report Category: NURSING Hasca - Hypertension Registry in Children and Adolescents: Pilot Study of National Database Viability JACQUELINE VAZ ALENCAR1, Caroline Naidon Coelho1, Clarissa G. Rodrigues10, Liliana Fortini Cavalheiro Boll1, Luiza Junqueira Trarbach Lovato2, Renata Povoas3, Nicole Saldanha de Souza5, Emily Justiniano6, Fernanda Consolim-Colombo7, Katia de Angelis8, Maria Claudia Irigoyen3, Danielle Irigoyen da Costa9 (1) Instituto de Cardiologia da Fundacao Universitaria de Cardiologia (IC/FUC) - Porto Alegre, RS - Brasil; (2) University of Technology Sydney (UTS) - Australia, Sidney; (3) Instituto do Coracao da FMUSP (InCor) - Sao Paulo, SP - Brasil; (4) Universidade Nove de Julho (Uninove) - Sao Paulo, SP - Brasil; (5) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) - Porto Alegre, Rio Grande do Sul - Brasil; (6) Hospital de Clinicas de Porto Alegre (HCPA) - Porto Alegre, RS - Brasil; (7) Universidade Nove de Julho (Uninove) - Sao Paulo, SP - Brasil; (8) Universidade Federal de Sao Paulo (Unifesp) - Sao Paulo, SP - Brasil; (9) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - Porto Alegre, Rio Grande do Sul - Brasil; (10) Global Research and Innovation Network (GRINN) - Curitiba, Parana - Brasil Introduction: Multicenter registries that represent the real-world provide important information, but there are few studies describing how to implement it. Objective: To describe the feasibility pilot project of a database on systemic arterial hypertension in children and adolescents in a reference hospital. Methods: Prospective, observational study to document and assess the feasibility of a multicenter registry of systemic arterial hypertension in children and adolescents. 3 steps were performed. Step 1: ethical aspects, contact with the school management, project pitch meeting and team training. Step 2: participants and workflow, variables included, action at school (screening and confirmatory phase). Step 3: evaluation of protocols, variables analyzed. Results: Sample composed of 80 students, average age of 15.73 +- 0.77 years, 77.5% female and 22.5% male. The mean BMI was 23.58 +- 4.11 kg. Students who presented at least two altered measured pressures in the screening phase were: altered BP 42 (52.5%) and normal BP 38 (47.5%). In the Confirmatory Phase: 22 (32.8%) maintained altered BP. These will be monitored at a specialized center. The data was analyzed with the "REDCap" software. After the viability of the Registry, other centers participated through training. Data quality reports were generated for quality control. Conclusions: The description of the methodology makes HASCA possible, enabling other centers to standardize data collection and promote the development of new health technologies, assisting in public policies on systemic arterial hypertension in children and adolescents. 109786 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Accuracy Index of Artificial Intelligence Platform in the Preparation of Electrocardiography Reports in Adult Intensive Care Unit FIRMINO HAAG FERREIRA JUNIOR1, Rosa Maria da Costa Simoes1, Diany Priscilla Oliveira1, Carolina Vieira1 (1) Hospital Geral de Sao Mateus Objective: To analyze the accuracy index of electrocardiogram reports performed in Intensive Care, reported by an artificial intelligence platform, compared with reports performed by cardiologists in person. The electrocardiograms were randomly assigned and reported "blind" to the results provided by the artificial intelligence, and then both results were compared. Report: Thirty (30) electrocardiograms of different patients were analyzed, randomly chosen, admitted to an intensive care unit, with a baseline diagnosis of cardiovascular diseases. Among the electrocardiograms analyzed, artificial intelligence was able to accurately diagnose 16 (sixteen) cases of inactive zone/myocardial infarction, 2 (two) cases of ST segment elevation, 2 (two) cases of atrial flutter, 5 (five) cases of atrial fibrillation, 5 (five) cases of diffuse changes in ventricular repolarization, 1 (one) case of left ventricular overload, 1 (one) case of anterior superior divisional hemiblock. Artificial Intelligence was able to identify electrode failures, as it did not consider the report. There was 100% compatibility of the artificial intelligence reports with the reports prepared by the cardiologists in person. Conclusion: The introduction of new technologies such as artificial intelligence producing reports in electrocardiography is of significant importance, due to the reliability of the reports presented, not different when compared with reports prepared by experienced cardiologists in person, being therefore an important tool in helping to physicians in identifying and confirming the diagnosis, especially for non-specialists, often present in emergency services and intensive care units. 109612 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Use of Capnography in Differentiating Non-Heart and Non-Pulmonary Disease as Cause of Dyspnea in Hospitalized Individuals ALEXANDRA CORREA GERVAZONI BALBUENA DE LIMA1, Caroline Barreto Cavalcanti1, Paula Fernandes Freitas Lima1, Barbara Cunha Barreto2, Bruno Ramos Carneiro2, Gabriela de Oliveira Silva2, Maria Alice Ramalho Bragatto2, Luis Moreira da Silva de Azevedo Meireles3, Sergio Henrique Rodolpho Ramalho4 (1) North Wing Regional Hospital - Brasilia - Brazil; (2) School of Health Sciences - Brasilia - Brazil; (3) MDI Industrial, Salvador - Brazil; (4) Clinical Research Center of the Brasilia of the Dasa Hospitals Network - Brasilia - Brazil Background: Rapid differentiation the cause of dyspnea from other heart or respiratory causes, is very important for choosing an appropriate therapy. Capnography is a non-invasive and accurate method to measure end-tidal carbon dioxide (PETCO2) and can help physicians in some critical situations. Although this is not used in many emergency situations and it is not used routinely in the emergency department, its application is increasing in many emergency situations, such as patients undergoing mechanical ventilation, procedural sedation and analgesia, pulmonary disease, heat failure, shock, metabolic disorder and trauma. Aim: To evaluate the PETCO2 in differentiating heart and/or pulmonary disease from non-heart and non-pulmonary related dyspnea in hospital setting. Methods: This was observational prospective study performed in the North Wing Regional Hospital, Brasilia, Brazil, August 2021-Febuary 2022. 254 Adults, conscious and spontaneous breathing hospitalized individuals were evaluated and divided in four groups of patients: heart disease (heart failure, ischemic heart disease) group 1 (n = 54), pulmonary disease (chronic obstructive pulmonary disease, asthma) group 2 (n = 68), heart and pulmonary disease group 3 (n = 74) and non-heart and non-pulmonary disease group 4 (n = 56). PETCO2 was measured by a portable capnograph, using a nasal catheter, without supplemental oxygen. Results: The groups were similar in age (group 1 62.2 +- 15,7 vs group 2 64.5 +- 18.0 vs group 3 62.0 +- 15.6 vs group 4 66.9 +- 17.4, p = 0.33) and gender (male, group 1 23% vs group 2 26% vs group 3 28% vs group 4 22%, p < 0.82). The PETCO2 was lower and similar in the heart and/or pulmonary groups and higher in non-heart and non-pulmonary group (group 1 29.2 +- 6.9 vs group 28.6 +- 5.7 vs group 3 28.7 +- 5.8 vs group 4 31.2 +- 5.0, p = 0.05). The PETCO2 in non-heart and non-pulmonary disease (area under the curve, 0.63; 95% confidence interval, 0.57-0.71, p = 0.03). Conclusion: The PETCO2 was able to screen individuals without heart and pulmonary disease in treatment of dyspnea in a public hospital. Capnography can be an easy, cost-effective and non-invasive tool to evaluate dyspnea and does not require cooperation of the patient. Other studies are necessary to different heart from pulmonary disease as cause of dyspnea. 109619 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myopericarditis Detected by Magnetic Resonance in Long COVID-19 RENATA JUNQUEIRA MOLL BERNARDES1, Julia Barroso1, Andrea Silvestre de Sousa1, Eduardo Schaustz1, Joao Dario Mattos1, Emiliano Medei1, Olga Ferreira de Souza1, Denilson de Campos Albuquerque1, Ana Cristina Baptista da Silva Figueiredo1, Mariana Tortelly1, Juliana Ferreira1, Gabriel Cordeiro Camargo1 (1) D'Or Institute for Research and Education, Rio de Janeiro, Brazil Background: The pathophysiological mechanisms associated with cardiac symptoms in post-acute COVID-19 are still poorly understood. A high prevalence of myocardial injury, associated with higher in-hospital mortality has been reported and one of the postulated mechanisms is an autoimmune inflammatory response. Cardiovascular magnetic resonance (CMR) is the best non-invasive method for the assessment of myocardial and pericardial inflammation, allowing the detection of edema and fibrosis. AIM To characterize the presence and prevalence of myopericardial inflammation in a population with a high prevalence of cardiac injury, recently discharged from COVID-19 hospitalization. Methods: In this prospective study, 190 hospitalized COVID-19 patients with clinical or laboratory cardiovascular abnormalities were included in a multicentric registry between November 2020 and December 2021. After discharge, all patients were contacted and 48 consented to return for CMR exam. Results: Of 48 included patients, 33 (68.8%) were male, the mean (SD) age was 57.0 (18.9) years, 24 (50%) were hypertensive and 12 (25%) had diabetes. Chronic cardiac disease was reported in 6 (12.5%), asthma in 4 (8.3%), and chronic obstructive pulmonary disease in 3 (6.3%). Thirty-one patients (64.6%) were overweighed and 37 (77.1%) had myocardial injury detected by increased troponin levels. The median (IQR) time interval between hospital admission and CMR was 74 (26-157) days. Myocardial late gadolinium enhancement (LGE) was observed in 20 (41.7%) patients, including 5 with subendocardial, 11 mesocardiac, and 4 with transmural LGE. Patients with transmural and subendocardial LGE were diagnosed with ischemic heart disease (5), hypertrophic myocardiopathy (2), and right ventricular muscular band (1). Fourteen patients (32.6%) had pericardial LGE, and the prevalence of this finding reduced from 41.7% to 30% and 11%, according to the time interval from hospital discharge to the CMR exam (0-3, 3-6, and 6-12 months, respectively). Small pericardial effusion was detected in 11 (25.6%) patients, and the frequency decreased from 37.5% to 10% and 11%. Conclusion: There is a high incidence of post-COVID myopericardial inflammation in patients who presented with cardiac abnormalities during acute illness, particularly myocardial injury. These findings indicate that myocardial injury may be related to late myocardial inflammation and might explain some of the long-term cardiovascular symptoms of COVID-19. 109651 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Remote Monitoring Application for Patients with Heart Failure: Pilot Randomized Clinical Trial ANA CARLA DANTAS CAVALCANTI1, Ana Carla Dantas Cavalcanti1, Lyvia da Silva Figueiredo1, Jessica Santos de Souza Leal1, Mellissa Barreto Oliveira Da Silva1, Flavio Luiz Seixas1, Caroline Barboza Braga1, Kelly Maria Augusta Tavares Bentes1, Jose Paulo de Mello Gomes1, Paula Vanessa Peclat Flores1, Evandro Tinoco Mesquita1 (1) Universidade Federal Fluminense Introduction: Heart failure is a clinical condition associated with morbidity and mortality, and it is necessary to manage the disease, relieve symptoms, prevent hospitalization and reduce mortality. Therefore, the use of mobile applications represents a strategy to optimize care. Objective: To compare self-care, quality of life, and depressive symptoms in patients with chronic heart failure using a mobile app with conventional follow-up. Method: The study was carried out in two phases, the first, a technological development study, and the second, a (pilot) randomized clinical trial. For the application development, the following software was used: Android Studio, Flutter and the Android operating system. Prospective validation was carried out with experts in heart failure through the System Usability Scale (SUS). In the pilot study, patients were divided into two groups. Patients in the intervention group used the application for 30 days, and patients in the control group used the conventional telephone follow-up. Outcomes were assessed using the European Heart Failure Selfcare Behavior Scale, the Minnesota Living with Heart Failure questionnaire, and the Beck Inventory. Data were analyzed using SPSS v.24 and a repeated-measures ANOVA. The study was registered in ReBEC (RBR-2w7wkb) and approved by an Ethics Committee. Results: The "Card.io" application features, as a resource, the sending of notifications and alarms reminding the patient of a certain action defined by the professional. The prospective validation was performed by 39 experts, mostly nurses (89.7%), with a mean age of 33 years, mostly female (82.1%), and 35 (89.7%) residing in Brazil. The application was considered excellent based on the SUS score. The pilot clinical trial was carried out with 42 patients. There were significant differences in the interaction regarding depressive symptoms (p = 0.016), self-care (p = 0.019), and quality of life (p < 0.001). Conclusion: The Card.io application for remote monitoring effectively improves the quality of life of patients and offers an alternative for healthcare professionals, with an innovative and low-cost proposal that can be implemented in healthcare services. 111068 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Prognostic Relevance of Quality of Care Indicators in the Treatment of Acute Myocardial Infarction RICARDO MOURILHE-ROCHA1, Bruno Reznik Wajsbrot1, Marcelo Luiz da Silva Bandeira1, Julia Paulo Mourilhe Rocha1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Eric Costa de Almeida1, Roberta Siuffo Schneider1, Ricardo Mendes Carneiro1, Claudia Lanzillotti Weksler1, Fernando Oswaldo Dias Rangel1, Daniel Xavier de Britto Setta1 (1) HOSPITAL PRO-CARDIACO Background: Measuring the quality of care indicators enable the recognition of weaknesses in health care. Based on this assessment, it will be possible to improve outcomes. Objectives: To evaluate the quality of care based on ventricular dysfunction, length of stay, coronary angioplasty and hospital mortality rates. Materials and Methods: Observational, retrospective, cohort study of 398 patients admitted with a diagnosis of AMI, with and without ST-segment elevation between January 2018 and January 2022; 69.3% male with a mean age of 65 years. Data were analyzed by the SPSS software. Results: They had the following comorbidities: 47.5% dyslipidemia, 77.9% hypertension, 50.5% previous CAD, 41.2% diabetes, 8.5% heart failure, 37.2% stroke, 15.1% coronary artery bypass surgery, 29.6% previous AMI, 10.1% chronic kidney disease, 43.0% smoking, and 10.3% atrial fibrillation. There were 31.2% with STEMI and 68.8% with NSTEMI, with 83.4% in Killip I, 8.4% in II, 3.1% in III, and 5.0% in IV. The median length of stay was 4 days (IQR 3-8) in the overall population, 4 days in NSTEMI and 5 days in STEMI; p = 0.02. The rates of events at discharge in the overall population and subgroups were: hospital mortality = 7.5% (4.7%, NSTEMI and 13.7%, STEMI; p = 0.002), ventricular dysfunction = 34.4% (28.1%, NSTEMI and 49.1%, STEMI; p < 0.001), being mild dysfunction in 15.5%, moderate 12.6% and severe 5.3%. The angioplasty rate was 79.1% (74.4% NSTEMI and 89.5% STEMI; p < 0.001). Conclusions: The mortality rate was higher than predicted by the Killip score. The incidence of ventricular dysfunction was high, but it was not possible to determine how many of these patients presented ventricular dysfunction prior to the event. The length of hospital stay was within the recommended range and the coronary angioplasty rate was also high. 111069 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Functional Capacity of Individuals Post Infection by COVID-19 Treated for Cardiopulmonary Rehabilitation in Home Based Format ANA INES GONZALES1, Ana Ines Gonzales1, Guilherme Michels1, Jackson da Silva Gullo1 (1) Universidade Estacio de Santa Catarina - Sao Jose Introduction: Studies on "Long Covid" suggest that long-term persistent clinical manifestations can last even months after infection. In this sense, post-covid rehabilitation programs are essential. Due to the restrictions imposed by the pandemic, carrying out rehabilitation programs in closed environments has become a concern, leaving home rehabilitation as the only option, also called Home Based (HB). Objectives: To verify the benefits of a post-covid-19 cardiopulmonary rehabilitation program in Home Based format. Method: Longitudinal, interventional study, with an accessibility sample, with individuals of both sexes, >=30 years old, with a clinical diagnosis of COVID-19 infection by the reverse-transcriptase polymerase chain reaction (RT-PCR) method, already completed, and who have remained with cardiopulmonary complications. Patient recruitment occurred publicity on social media and radio. The recruited individuals were submitted to the 30-second sit-and-stand test (30CST) and the 2-minute stationary gait test (2MWT) remotely during the post-rehabilitation program period. The intervention protocol took place synchronously, in a home-based format, using video calls via Whatsapp app, based on: 1) respiratory kinesiotherapy exercises, 2) aerobic training; 3) resistance training with localized muscle strength exercise, 4) stretching, two days a week for approximately 60 minutes, and individuals performed rehab with the help of tutors. The Borg Subjective Scale was used to monitor the intensity of the exercises, and should remain between 3 and 4 points. Results: Twenty-eight individuals were treated, 12 men (43%) and 16 women (57%), mean age of 50 +- 5 years, who performed 16 +- 1.2 sessions. There was a mean improvement of 8 +- 1.2 elevations (p = 0.002) to 30CST and 10 +- 2 elevations (p = 0.01) of the dominant limb to TME2 in the post-intervention values, with Borg subjective scale to 2MWT falling from 5 to 3 during testing after intervention. Conclusions: A home-based post-covid 19 rehabilitation program promotes improvement in functional capacity, proving to be an applicable and beneficial intervention method for these patients. 110374 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Exercise Limitation Mechanisms in COVID-19 Survivors FERNANDA SAHAR LUCAS VIDAL DOMECG2, Fabricio Braga da Silva1, Marcelo Kalichsztein3, Gustavo Nobre3, Jose Kezen3, Gabriel Espinosa1, Christiane Prado1, Marcelo Faccio1, Illan Gotlieb3, Ronaldo Leao Lima2 (1) Laboratorio de Performance Humana; (2) Universidade Federal do Rio de Janeiro; (3) Casa de Saude Sao Jose Background: Limited exercise capacity (LEC) is a prevalent complaint in COVID-19 survivors. The cardiopulmonary exercise test (CPET) is the gold standard in determining LEC mechanisms. Objectives: To analyze LEC mechanisms in COVID-19 survivors of different clinical severities and compare them with a non-COVID-19 control population. Materials and methods: Cross-sectional analysis of CPET was performed between July/19 and March/21. Patients were divided into 3 groups: mild COVID-19(L-Cov; outpatient treatment); Severe COVID-19(G-Cov; hospital admission) and non-COVID-19(N-Cov; CPET performed before the start of the pandemic). LEC was defined as VO2 <85% of predicted at peak exercise and classified as: cardiocirculatory(CC), ventilatory(VEN), mixed(MIX; a combination of CC and VEN), or aerobic deconditioning(AD). Furthermore, the prevalence of findings suggestive of vascular-pulmonary involvement(Vas-Pul) was compared between the groups. Based on the values of end-tidal CO2 pressure and the ratio between ventilation and CO2 production, patients were classified at the first ventilatory threshold according to the probability of Vas-Pul involvement as non-suspected, suspected, likely, and very likely. Results: 702 patients were included(61.1% men; 52.1 +- 14.3 years), 310(44.2%); 305(43.4%) and 87(12.4%) N-Cov, L-Cov and G-Cov, respectively. Table 1 shows the LEC mechanisms between the groups(kh2 = 3.76; df = 6;p = 0.709). Table 2 shows the probability of Vas-Pul involvement(kh2 = 34.26; df = 6; p < 0.001). In the posthoc analysis, a probable and very likely pattern was higher in the G-Cov group (p < 0.05). Conclusion: AD was the main mechanism of exercise limitation, followed by cardiocirculatory, ventilatory and mixed limitation (CC+Vent.). 110375 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Early Triage Echocardiography to Predict Outcomes in Patients Admitted with COVID-19 - a Multicenter Study BRUNO RAMOS NASCIMENTO1, BRUNO RAMOS NASCIMENTO, Maria Carmo Pereira Nunes1, Nicholas Ollberding2, Allison Hays3, Pranoti Hiremath3, Federico Asch4, Chad League4, Chris Fung5, Laurie LeBouef5, Craig Sable6, Andrea Zawacki Beaton2 (1) Servico de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaude do Hospital das Clinicas da UFMG, Belo Horizonte - MG, Brazil; (2) The Heart Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati - OH, United States; (3) Cardiology, The Johns Hopkins Hospital, Baltimore - MD, United States; (4) The Heart and Vascular, MedStar Washington Hospital Center, Washington - DC, Unites States; (5) Cardiovascular Center, University of Michigan Hospital, Ann Harbor - MI, United States; (6) Cardiology, Children's National Health System, Washington - DC, United States Introduction: Cardiac involvement impacts prognosis of COVID-19, especially in critically ill patients. We aimed to assess the prognostic value of limited cardiac assessment by bedside triage echocardiography (echo) in patients admitted to emergency departments (ED) in the United States with COVID-19. Methods: Patients admitted in 4 reference US EDs with confirmed COVID-19 underwent triage echo within 72h of symptom onset, with remote interpretation. Clinical and laboratory data, as well as COVID-19 symptoms, were collected. A comprehensive echo protocol, with quantitative assessment, was applied in high-resource units, while low-resource EDs utilized a focused qualitative protocol. Association between echo variables, demographics and clinical data with all-cause mortality and intensive care unit (ICU) admission was assessed; factors significant at p < 0.10 were put into multivariable models. Results: A total of 399 patients were enrolled (137 from low-resource EDs), 41% women, with a mean age of 62 +- 16 years. Mean oxygen saturation on presentation was 92.3 +- 9.2%, and the average number of comorbidities was 2.1 +- 1.7. Compared to survivors, non-survivors were older (68 +- 12 vs. 60 +- 17 years, p < 0.01), had lower oxygen saturation (88.8 +- 12.0% vs. 93.1 +- 8.2%, p < 0.01), were more likely to have a chronic condition (2.6 +- 1.6 vs. 2.0 +- 1.7 comorbidities, p = 0.01) and had lower LV ejection fraction (50.3 +- 19.7 vs. 58.0 +- 13.6, p < 0.01). 101 (25%) patients had moderate/severe LV dysfunction and 131 (33%) had moderate/severe RV dysfunction. Older and lower oxygen saturation were independently associated with death (OR = 2.14 (95%CI 1.06-4.32) and OR = 0.67 (95%CI 0.53-0.85), respectively) and ICU admission (OR = 0.65 (95%CI 0.46-0.94) and OR = 0.48 (95%CI 0.37-0.64)). No echo variables, including LV and RV function, were independent predictors of outcomes. The mortality model comprised of age, sex, count of co-morbid conditions, and oxygen saturation, had a C-statistic = 0.68 and Brier score = 0.14. The inclusion of LV/RV dysfunction, and pericardial effusion did not improve performance (C-statistic = 0.67, Brier score = 0.15). A similar pattern was observed for the ICU admission model. Conclusion: In patients admitted with COVID-19 and undergoing early echo triage, independent predictors of death and ICU admission were age and oxygen saturation. Despite differences in baseline LVEF, no echo variables were independently associated with unfavorable outcomes. 109741 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Patent Foramen Ovale: Percutaneous Closure of the Defect as a Therapeutic Alternative for Patients Over Sixty Years of Age MARCELO SABEDOTTI1, Bibiana Guimaraes Maggi2, Gabriel Almeida Krul2, Elisa Rocha Nonemacher2, Rafaela Oliveira Leite2 (1) Unimed Nordeste; (2) Fundacao Universidade de Caxias do Sul Introduction: Percutaneous patent foramen ovale (PFO) closure effectively prevents embolic ischemic stroke. However, most studies do not include patients over sixty years of age. This group of patients usually has other causes of ischemic stroke, the main ones including cardiac arrhythmias, small cerebral vessel disease, and atherosclerosis. The present study aims to support the hypothesis that PFO closure is safe in patients over 60 years of age. Objective: To assess the safety of percutaneous PFO closure in patients over sixty years. Methods: A retrospective, single-center cohort study. Patients aged over sixty years who underwent percutaneous PFO closure to prevent recurrence of cerebrovascular events at Hospital Unimed Nordeste do the Rio Grande do Sul, between September 2019 and January 2022 were included. Results: From June 2019 to March 2022, 15 patients were submitted to percutaneous PFO closure (Table 1), with a mean age of 70 +- 7 years, 60% were female. All patients had PFO with ISA, transcranial ultrasound (TU) with more than 100 high-intensity signals (HITS), Holter without atrial fibrillation, and hematological investigation without coagulopathies. As for medications, 53.3% of patients were being treated with Acetylsalicylic Acid (ASA) associated with clopidogrel and 46.7% using anticoagulants being 26% Dabigatran, 13% Apixaban, and 6% Rivaroxaban. Two days before the procedure and three months after, all remained with ASA and clopidogrel. There weren't any complications during the procedure. In 30 days, echocardiographic control showed a foramen completely occluded, without a residual shunt. Conclusion: The procedure for closing PFO in patients over 60 years of age is effective and safe. Careful evaluation is important, including shunt quantification by TU, exclusion of coagulopathies, arrhythmias, and atherosclerotic causes of ischemic stroke. A high-risk PFO morphology can also influence the decision to carry out closure. Data from studies in patients over 60 years of age are limited and additional studies are needed to assess the benefits of this treatment as the population grows old. 109758 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Association between Sex and Therapeutic Targets of Lipid Profile in Individuals with Previous Acute Myocardial Infarction: Subanalysis of Dica-Nuts Trial ERLON OLIVEIRA DE ABREU SILVA1, Erlon Oliveira de Abreu-Silva1, Angela C. Bersch-Ferreira1, Rachel H. Vieira Machado1, Lucas R. Silva1, Erica R. Ribeiro Sady1, Debora H. Kodama Miyada1, Bernardete Weber1, Aline Marcadenti1 (1) Hcor Research Institute (IP-Hcor), Hcor, Sao Paulo, Sao Paulo, Brazil. Background: Differences between sexes regarding therapeutic targets of lipid profile in populations at very high cardiovascular risk are not fully elucidated. Objective: To evaluate the association between sex and therapeutic targets for LDL-cholesterol (LDL-c) and non-HDL-cholesterol (NHDLc) in individuals diagnosed with acute myocardial infarction (AMI). Methods: Cross-sectional analysis with baseline data from a multicenter randomized clinical trial (DICA-NUTS Trial, NCT03728127) conducted among subjects >=40 years with previous AMI (60 to 180 days). Sociodemographic, clinical and lifestyle data were collected using specific questionnaires. Therapeutic goals of LDL-c (<50 mg/dL) and NHDLc (<80 mg/dL) were defined according to American Heart Association guidelines. Binary logistic regression was used to evaluate potential associations adjusted for confounders. Results: In total, 471 individuals with a mean age of 59.6 +- 9.3 years were evaluated; 72.2% were men, the estimated monthly household income was US$ 180.00, 10.2% were smokers and 61.8% had AMI with ST-segment elevation (STEMI). The prevalence of married individuals was higher among men compared to women (61.5% and 45.8% respectively, P = 0.001), and among women there were higher proportions of high levels of physical activity (35.9% vs. 22.9%, P = 0.003) and from lower social classes (D/E classification) (68.7% vs. 53.2%, P = 0.002). The use of simvastatin was more frequent (52.4%), followed by rosuvastatin (21.4%) and atorvastatin (21%), with no difference between men and women. Among men, 14.4% and 18.2% had LDL-c and NHDL-c concentrations in line with the recommended targets; these prevalences were higher than those observed in women (LDL-c: 6.9% [P = 0.028]; CNHDL: 8.4% [P = 0.007]). After adjusting for age, marital status, social class and physical activity levels, there was an association between male sex and achieving therapeutic targets for NHDL-c (OR 2.04; 95%CI 1.003-4.15), but not for LDL-c (OR 1.84; 95%CI 0.84-4.03). However, being in lower social classes conferred a 74% lower chance of reaching LDL-c targets (OR 0.26; 95%CI 0.07-0.92) and 81% lower chance of reaching NHDL-c targets (OR 0.19; CI95% 0.06-0.59) regardless of age, sex, marital status, and levels of physical activity. Conclusions: There are differences between sexes regarding therapeutic targets for LDL-c and NHDL-c. However, social class appears to be a major determinant. 109784 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Trabecular Bone Score and Body Composition in Elderly Patients with Heart Failure RAFAEL BUARQUE DE MACEDO GADELHA1, Mirela Avila Litvin1, Lucian Batista de Oliveira1, Cybelle Luza Costa1, Jessica Myrian de Amorim Garcia1, Francisco Bandeira1 (1) Hospital Agamenon Magalhaes Introduction: Heart failure (HF) is associated with a higher risk of osteoporotic fractures, with few studies evaluating the factors related to this increase. The trabecular bone score (TBS) is a tool to assess bone microarchitecture, appearing as an independent predictor of fracture risk and gaining greater importance in populations where there is an increased risk of these events even with preserved bone mineral density (BMD). Objectives: To evaluate TBS in elderly patients with HF, comparing it with BMD results and with echocardiographic and body composition parameters. Methodology: Observational, cross-sectional and analytical study involving elderly individuals (>=65 years) diagnosed with HF, followed up in a cardiology service from August 2020 to August 2021. Patients with contact isolation, lipodystrophies or body mass index >37 kg/m2 were excluded. All were submitted to dual energy X-ray absorptiometry (DXA) for analysis of body composition, BMD and TBS. Results: Sixty patients were evaluated, with a mean age of 73.4 +- 5.3 years, 51.7% of which were female. The mean left ventricular ejection fraction (LVEF) was 46.5 +- 16.1%, with 40% having reduced LVEF (<40%). BMD showed osteoporosis (T-Score <= -2,5) in 38.3% and osteopenia (T-Score between -1.0 and -2.5) in 46.7%, while TBS showed bone degradation (TBS < 1,230) by 35% and partial degradation (TBS between 1.230 and 1.310) by 30%. There was a statistically significant association between some degree of degradation indicated by TBS with lower lumbar spine BMD (0.99 +- 0.22 g/cm2 x 1.21 +- 0.24 g/cm2; p < 0.001), femoral neck (0.78 +- 0.15 g/cm2 x 0.88 +- 0.08 g/cm2; p < 0.001) and total femur (0.86 +- 0.16 g/cm2 x 0.98 +- 0.13 g/cm2; p = 0.006). There was no association between degraded/partially degraded TBS and lower LVEF means (47.49 +- 16.42% x 44.50 +- 15.66%; p = 0.523). Regarding body composition, an association was observed between degraded/partially degraded TBS with lower means of lean mass in the upper limbs (4.47 +- 1.04 kg x 5.16 +- 1.50 kg; p = 0.041). Conclusion: Low BMD and changes in bone microarchitecture are frequent in elderly patients with HF. Degradation of bone microarchitecture was associated with a reduction in appendicular lean mass. 109799 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Accuracy Index of Artificial Inteligence Platform in the Preparation of Electrocardiography Reports in Adult Intensive Care Unit FIRMINO HAAG FERREIRA JUNIOR1, Rosa Maria da Costa Simoes1, Diany Priscilla Oliveira1, Carolina Vieira1 (1) Hospital Geral de Sao Mateus Objective: To analyze the accuracy index of electrocardiogram reports performed in Intensive Care, reported by an artificial intelligence platform, compared with reports performed by cardiologists in person. The electrocardiograms were randomly assigned and reported "blind" to the results provided by the artificial intelligence, and then both results were compared. Results: Thirty (30) electrocardiograms of different patients were analyzed, randomly chosen, admitted to an intensive care unit, with a baseline diagnosis of cardiovascular diseases. Among the electrocardiograms analyzed, artificial intelligence was able to accurately diagnose 16 (sixteen) cases of inactive zone/myocardial infarction, 2 (two) cases of ST segment elevation, 2 (two) cases of atrial flutter, 5 (five) cases of atrial fibrillation, 5 (five) cases of diffuse changes in ventricular repolarization, 1 (one) case of left ventricular overload, 1 (one) case of anterior superior divisional hemiblock. Artificial Intelligence was able to identify electrode failures, as it did not consider the report. There was 100% compatibility of the artificial intelligence reports with the reports prepared by the cardiologists in person. Conclusion: The introduction of new technologies such as artificial intelligence producing reports in electrocardiography is of significant importance, due to the reliability of the reports presented, not different when compared with reports prepared by experienced cardiologists in person, being therefore an important tool in helping to physicians in identifying and confirming the diagnosis, especially for non-specialists, often present in emergency services and intensive care units. 109805 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Cardiobreath Application Slow Deep Breath for Health and Performance CLAUDIA FETTER1, Maria Claudia Irigoyen3, Liliane Appratto de Souza1 (1) Instituto de Cardiologia do Rio Grande do Sul; (2) TECNOPUC/RS; (3) Incor/USP CardioBreath is an application for mobile and tablets available at Google Play and Apple Store (only in Portuguese). This application prescibes, teaches and evaluates slow deep breath for health and performance. The main objective of Cardiobreath is to offer to users an option for practicing respiratory exercises at rates slower than individual spontaneous rate in order to increase vagal modulation, decrease arterial pressure, increase strenght and resistance of respiratory muscles and cardiorespiratory fitness. Together these benefits may represent great achievements in health and performance. Handling CardioBreath App allows the user to be in touch with their own biological signals like respiratory rate and heart rate. For slow breath exercises prescription, some biological information like age, gender, weight, height (and body mass index is calculated inside the app), and including other conditions like smoking, sedentary life style, hypertension, diabetes, obstructive sleep apnea and cardiopaty make a score that drive users to their more reccomendable band of respiratory exercise. Users may chose on position: sit, standing or lying. Audio lessons are available about posture and respiratory technique (victoriuous brath/ujjayi pranayama from yoga). The prescription includes basic, intermedium and advanced exercises in order to identify progression stages. There is the option for the user to chose the respiratory exercise rate (cycles per minutes). The respiratory frequencies of exercise may vary from 15 to 2 cycles per minute using a metronome, either visual as bell sign, or audio lesson recorded. Other option is four frequencies of exercise with respiratory hold (or pause), either in inspiratory or expiratory hold, with metronome, bell or audio lesson. Users may follow their progress by a graphic of exercise respiratory rate X time of exercise, and other functionality available is heart rate before and after the exercises, which are also represented in graphic. And the most easy lesson of the application is available at the first screen, is the 17 minutes guided relaxation based on a specific miofascial and visceral relaxation. CardioBrreath was created in 2018 and a second version is being developed through a grant (Programa doutor Empreendedor/FAPERGS/CNPQ SEBRAE) and will be availabe in June. Any other information may be found at www.cardiobreath.com and includes more functionalities and gamification in order to increase adherence of users. 109813 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Main Diagnoses Found and Potential for Acertivity in the use of Artificial Intelligence Platform in the Preparation of Electrocardiogram Reports in Adult Intensive Care Unit FIRMINO HAAG FERREIRA JUNIOR1, Rosa Maria da Costa Simoes1, Diany Priscilla de Oliveira1, Carolina Vieira1 (1) Hospital Geral de Sao Mateus Objective: To analyze the main diagnoses found through the use of an artificial intelligence platform for electrocardiogram reports performed in adult intensive care. Patients were randomly selected from November 2021 to March 2022. Results: Seventy-one (71) electrocardiograms of randomly chosen patients admitted to an intensive care unit with a baseline diagnosis of cardiovascular disease were analyzed. Among the analyzed electrocardiograms, artificial intelligence was able to accurately elaborate the main diagnoses: 13 (thirteen) patients had electrocardiographic alterations compatible with diffuse alteration of ventricular repolarization; 09 (nine) patients had a diagnosis of acute myocardial infarction with ST segment elevation; 12 (twelve) patients had atrial fibrillation; 7 (seven) patients had a diagnosis of subepicardial ischemia and 01 (one) patient had a diagnosis of atrioventricular block. Of the cases analyzed, 28 patients had an electrocardiogram within the normal range. Artificial intelligence was able to identify electrode failures, as it did not consider the report. There was 100% compatibility of the Artificial Intelligence reports with the clinical diagnoses of the patients. Conclusion: In addition to the precise diagnosis that allowed guiding directed procedures in each case, artificial intelligence was significantly important due to the reliability of the reports presented, helping physicians in the identification and confirmation of the diagnosis, becoming an important tool in the approach of critical patients for physicians not specialists working in intensive care units 110123 Modality: E-Poster Researcher - Non-case Report Category: NURSING Transitional Care Program for Patients with Heart Failure and Recent Hospitalization Improves Self-Care, Quality of Life and Knowledge of the Disease: Experience of a Public Center in Brazil JULIANA DE MELO VELLOZO PEREIRA TINOCO1, Ana Carla Dantas Cavalcanti1, Bruna Lins Rocha de Padua1, Beatriz Paiva e Silva de Souza1, Tereza Cristina Felippe Guimaraes2, Evandro Tinoco Mesquita1 (1) Universidade Federal Fluminense; (2) Instituto Nacional de Cardiologia Background: Heart failure (HF), a syndrome that requires complex therapeutic regimens, is associated with high rates of hospitalization. Transitional care programs are crucial for encouraging patients to practice self-care and for minimizing preventable readmissions. These interventions are essential in promoting self-care for HF hospitalized patients. However, brazilian clinical evidence on patients from The "Sistema Unico de Saude" is still scarce. Objective: To compare the effect of intervention with transitional care versus conventional hospital follow-up on self-care skills, knowledge of the disease, quality of life and depressive symptoms of patients hospitalized with HF. Methods: A blind, randomized clinical trial of 74 patients with HF admitted to two quaternary-care hospitals in Rio de Janeiro was conducted. Criteria for inclusion: age >= 18 years; clinical diagnosis of HF, irrespective of etiology; hospitalization for decompensated HF. Criteria for exclusion: hemodynamic instability; neurological/cognitive impairment reported in medical records; participation in previous studies involving educational interventions; perioperative hospitalization; transfer to another hospital; undergoing preparation for heart transplantation. The intervention group (IG) received transitional-care follow-up in the form of five encounters during hospitalization and weekly post-discharge telephone calls for four weeks. The control group (CG) received conventional hospital follow-up. Outcomes scored: self-care, quality of life, knowledge of the disease and depressive symptoms within 30 days post-discharge. Blinding was achieved by designating separate teams for evaluation, randomization, and intervention. Sample size calculation was based on a pilot study of 70 patients. Data were treated with repeated-measures ANOVA and Fisher's exact test. Results: Thirty days post-discharge, the scores for IG patients, compared with CG counterparts, were higher for self-care maintenance (74.3 vs. 44.2; p < 0.001), self-care confidence (79.3 vs. 56.4; p < 0.001), knowledge of the disease (41.3 vs. 27.5; p < 0.001), and lower for quality of life (42.1 vs. 64.5; p < 0.001). There was no effect on self-care management skills and depressive symptoms. Conclusion: The transitional-care program improved the outcomes self-care maintenance, self-care confidence, knowledge of the disease and quality of life. Study is registred in Brazilian Registry of Clinical Trials (RBR-2dpc6b). 109845 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Use of Pet-Ct to Investigate the Genesis of Ventricular Arrhythmias in Chagas Disease RENEE SARMENTO DE OLIVEIRA1, Renee Sarmento de Oliveira1, Renata Junqueira Moll Bernardes1, Adriana Soares Xavier de Brito1, Paulo Henrique Rosado de Castro1, Martha Valeria Tavares Pinheiro1, Sergio Salles Xavier2, Otacilio da Cruz Moreira2, Flavia Vernin de Oliveira Terzi1, Andrea Silvestre de Sousa1 (1) Instituto D'or de Pesquisa e Ensino; (2) Instituto Oswaldo Cruz/Fiocruz Background: Chagas cardiomyopathy is the most frequent and potentially severe manifestation of Chagas disease, with the highest morbidity among neglected tropical diseases. Although endemic in Latin America, it has become a global problem due to the migration of individuals to non-endemic areas. Sudden death is the main mechanism of death in chronic Chagas cardiomyopathy, being associated with ventricular tachycardia and may even occur in patients in the early stages of heart disease. In addition to fibrosis, persistent inflammation may be implicated in the genesis of arrhythmias. Strategies that identify patients at greater risk of developing complex ventricular arrhythmias in their different mechanisms of presentation would be able to guide the prophylaxis of sudden death more appropriately in chronic Chagas cardiomyopathy. Recent studies showed promising results using radionuclide imaging for the identification of areas of inflammation in the myocardium of patients with non-ischemic cardiomyopathies, such as sarcoidosis. Objective: To correlate the presence of persistent myocardial inflammation with FDG-18F and DOTATOC-68Ga PET-CT with the severity of ventricular arrhythmias and the presence of parasite in patients with chronic Chagas' heart disease. Methods: Two groups were included, totaling 24 patients. Group 1 consisted of patients with sustained ventricular tachycardia who required implantable cardioverter-defibrillator (ICD). Group 2 was the comparison group composed of patients at the same stage of Chagas heart disease (B1, B2 and C) but without complex ventricular arrhythmia. All patients underwent FDG-18F and DOTATOC-68Ga PET-CT, Holter, and polymerase chain reaction for trypanosoma cruzi. Results: The presence of the parasite in chronic Chagas cardiomyopathy was higher in patients from the ICD group (66.7%) compared to group 2 (33.3%). There was no statistical difference between the uptake of FDG-18F and DOTATOC-68Ga by PET-CT in both groups. Physiological increased uptake of FDG-18F may have jeopardized the analysis in some patients. Conclusion: The persistence of chronic parasitemia in Chagas' heart disease may be implicated in the genesis of arrythmia, increasing the risk of sustained ventricular arrhythmia; however, larger studies are necessary to investigate this association. PET-CT with FDG-18F and DOTATOC-68Ga are not currently recommended as markers or inflammation in Chagas cardiomyopathy. 111116 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Willingness to Forgive in Patients with Chronic Coronary Syndrome ADELLE CRISTINE LIMA CARDOZO1 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital; (3) Primavera Hospital Introduction: Despite advances in treatment, chronic coronary syndrome (CCS) persists as an important cause of morbidity and mortality worldwide. There is evidence of the influence of the disposition to forgive in the processes of illness and healing of patients with cardiovascular disease, including myocardial ischemia. Objectives: To evaluate the willingness to forgive in patients with CCS and its association with Spirituality/Religiosity. Methodology: This is an observational, cross-sectional, analytical study, whose sample included patients with CCS assisted at the cardiology outpatient clinics of three hospitals in Sergipe. Two scales were applied: DUREL (Duke Religious Index) and the BMMRS (Brief Multidimensional Measure of Religiosity and Spirituality), whose domain number 3 assesses forgiveness. This domain is composed of three items: I) disposition to self-forgiveness; II) disposition to forgive those who offend us; III) belief in God's forgiveness. Each item has an ordinal scale from 1 to 4, corresponding to responses: Never, Rarely, Often, and Always, respectively. The level of forgiveness is determined from the sum of the three items and ranges from 3 to 12. Student's t test was used for comparison between the groups, with the significance level set at 0.05. Results: Fifty-three patients with CCS were included, of which 50.9% were female. The mean age of patients was 62.2 +- 10.5 years. Regarding the clinical profile, 81.1% were hypertensive, 80.0% dyslipidemic and 46.2% had diabetes mellitus. Regarding the religious profile, 65.4% were Catholic, 23.1% Evangelical, 5.8% Spiritualist, 1.9% Umbandaist, 1.9% Atheist, and 1.9% believed in God but did not belong to any religion. The patients' religiosity was evaluated using the DUREL, and was divided into organizational, non-organizational, and intrinsic religiosity. Patients with high levels of organizational religiosity, non-organizational religiosity, and intrinsic religiosity showed higher levels of forgiveness compared to patients with low levels of religiosity in these categories (11.1 vs. 9.8; p < 0.05) (10.8 vs. 7.0; p < 0.001) (11.0 vs. 8.7; p = 0.001). Conclusions: The results show that CCS patients who have higher levels of religiosity are more likely to forgive themselves, forgive others, and believe in divine forgiveness when compared to patients with lower levels of religiosity. 109864 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Risk Score Elaboration for Stroke in Cardiac Surgery ELLEN HETTWER MAGEDANZ1, Joao Carlos Vieira da Costa Guaragna2, Luciano Cabral Albuquerque4, Fernanda Lourega Chieza3, Brenda Goncalves Donay1, Luize Mancuso Silva1, Jasseane De Borba Sparremberger Vitt1, Luiz Carlos Bodanese1 (1) PUCRS; (2) Hospital Divina Providencia; (3) Santa Casa de Misericordia de Porto Alegre; (4) Hospital Sao Lucas PUCRS Introduction: Stroke is a complication that causes considerable morbidity and mortality during the heart surgery postoperative period (incidence: 1.3 to 5%; mortality: 13 to 41%). Models for assessing the risk of stroke after heart surgery have been proposed, but most of them do not evaluate postoperative morbidity. Objective: The aim of this study was to develop a risk score for postoperative stroke in patients who undergo heart surgery with cardiopulmonary bypass. Methods: A cohort study was conducted with data from 4,862 patients who underwent surgery from 1996 to 2016. Logistic regression was used to assess relationships between risk factors and stroke. Data from 3,258 patients were used to construct the model. The model's performance was then validated using data from the remainder of the patients (n = 1,604). The model's accuracy was tested using the area under the receiver operating characteristic (ROC) curve. Results: The prevalence of stroke during the postoperative period was 3% (n = 149); 59% of the patients who exhibited this outcome were male, 51% were aged >= 66 years, and 31.5% of the patients died. The variables that remained as independent predictors of the outcome after multivariate analysis were advanced age, urgent/emergency surgery, peripheral arterial occlusive disease, history of cerebrovascular disease, and cardiopulmonary bypass time >=110 minutes. The area under the ROC curve was 0.71 (95% confidence interval 0.66-0.75). Conclusion: We were able to develop a risk score for stroke after heart surgery. This score classifies patients as low, medium, high, or very high risk of a surgery-related stroke. 110935 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Physical Active Patients with Stable Coronary Heart Disease Show Distinct Gut Microbiota Profiles ELISA ALBERTON HAAS1, Elisa Alberton Haas1, Wilson Jose Fernandes Lemos Junior2, Laura Treu3, Andrey Santos4, Mario Jose Abdalla Saad4, Francisco Rafael Martins Laurindo1, Protasio Lemos da Luz1 (1) Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; (2) Faculty of Science and Technology, Libera Universita di Bolzano, Bolzano, Italy; (3) Biology Department, University of Padova, Italy; (4) Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas, SP, Brazil Background: Regular physical activity supports cardiovascular disease (CVD) prevention through mechanisms that include: influences on inflammatory profile, on the autonomic nervous system and endothelial modifications. One potentially beneficial and overlooked mechanism of physical activity is its effects on the gut microbiota. Methods: This was a cross-sectional cohort analysis of 39 participants of a larger cohort (registered at ClinicalTrial.gov, NCT03232099), evaluating their baseline characteristics. Participants had established coronary artery disease (CAD), were male, aged 46-69 years, had BMI < 30, were stable and non-symptomatic. The cohort was divided into two groups: 21 physically active (PA) participants and 18 physically inactive (PI). The gut microbiota was evaluated with 16S amplicons, and the level of self-reported physical activity was calculated in metabolic equivalents (MET)-hour/week score (METs.h/wk). Patients were considered physically active when levels of Mets.h/wk were >5. A 3-day food frequency questionnaire obtained nutritional information regarding total calories, macronutrients and micronutrients. Results: The gut microbiota profile of PA and PI individuals were clearly separated by sparse partial least squares discriminant analysis. The main taxa that differed the PA group were Ruminococcaceae_UCG-014 and Coprococcus_2 eutactus, which are associated with reduced visceral adiposity and with butyrate production, respectively. Meanwhile, nutrient consumption was similar in the two groups. Conclusions: In patients with CAD, physical activity was associated with different and putative beneficial gut microbiota profile. These findings indicate that gut microbiota modifications further support the healthy mechanisms promoted by physical activity to reduce CVD. 109902 Modality: E-Poster Researcher - Non-case Report Category: NURSING Validation of an Educational Strategy for Capacitation of the Nursing Team on Management of Oral Anticoagulants ADRIANA DA COSTA COELHO1, Dasymar Martins da Silva Lucas1, Milena Preissler das Neves1, Geovane de Kassio Nunes2, Renata Flavia Abreu da Silva3 (1) Federal Hospital for State Servants - HFSE; (2) Hospital Pro Cardiac; (3) Federal University of the State of Rio de Janeiro - UNIRIO Introduction: The oral anticoagulants are widely prescribed drugs for treatment and prophylaxis of thrombotic diseases, and the antagonists of vitamin K, such as Warfarin, the main protagonists of this pharmaceutical class. Anticoagulation therapy requires specific knowledge from the nursing team for its safe management and training in service is necessary for the improvement of a qualified care, and constitutes a foundation between practice performed by the professionals and their instrumentalization. Objective: Describing the validation of an educational strategy for capacitation of the nursing team on the management of oral anticoagulants. Method: Methodological study with elaboration of tools such as word search puzzles and a checklist to be performed by the nursing team in the administration of oral anticoagulants, that was based on an integrative review. The theoretical validation of the products by experts was made by online questionnaire. The content validity index acceptable must be higher than 0.70. Results: The 16 experts agreed to take part in the research and evaluate the tools. The subject's profiles were: nurses with professional degrees between 14 and 20 years (43,8%) and working with anticoagulants between 8 and 11 years (37,8%); 8 (50%) of them participated in scientific events about oral anticoagulants in the last 5 years. The Content Validity Index by the experts was 0.83. The suggestions were accepted and modified for the final version of the tools. The statements that showed greater agreement (93,4%) were the ones stating the Content, that included nursing care management. The one that had the minor agreement was the item about the Title clarity (73,4%). Despite the high level of agreement, some experts suggested a few improvements to the word search puzzle, such as: replace the "Stop" sign carried by the character for an "Attention" one, and re-elaborate some sentences. Conclusion: The word search puzzle has been theoretically validated, therefore it should be used as an educational strategy for the patient's care in use of the oral anticoagulation by the nursing team. 109914 Modality: E-Poster Researcher - Non-case Report Category: PHYSICAL EDUCATION Viability of Hemodynamic Measures and Psychossocial Factors Screening in Gym Centers: Pilot Study CLAUDIA FETTER1, Jose Antonio Cacapietra Reteguy1, Juliana Bertoletti1 (1) Instituto de Cardiologia do Rio Grande do Sul Introduction: Sedentary lifestyle presents deleterious effects over human health and this condition may be reverted through the regular practice of physical exercise. Regular exercise practice offers benefits beyond physical health, with evidence to the improvement of psychosocial factors such as anxiety, depression and stress. Gyms are places destined to the practice of physical exercises, although most of it does not perform the follow-up of benefits to physical and mental health. Besides that, the strong appeal to the search of the perfect body very prevalent in this environment may exert a reverse effect of dissatisfaction with body image. Method: This pilot study about the viability of follow up of hemodynamic measures (blood pressure and heart rate) psychosocial factors through the DASS-21 (anxiety, depression, stress) and (brazilian scale of silhouette (body image) in gyms recruited 24 sedentary individuals for 4 weeks (men and women) with two weekly sessions of resistance exercises, and evaluated these psychosocial factors in order to verify the efficacy of the exercises and the viability of the follow up. 24 individuals, 12 women with mean age of 51 years and 12 men with mean age of 45 years took part in this research, assessed in one moment (T1) pre wash out of 4 weeks maintaining the sedentary condition, moment T2 immediately before initiating exercise and moment T3 at the end of the exercise intervention. The instruments used for the assessment were: Depression, Anxiety and Stress Scale (DASS-21) and the Brazilian Scale of Silhouettes for Adults. Data analysis was performed by GEE and significance level of p 0,05. Results: The results of the assessments of T3 were significant in relation to T2 for the variables Body Mass Index (BMI), Systolic Arterial Pressure (SAP) and Diastolic (DAS) and the three variables of DASS 21(anxiety, depression, stress) and relation of actual silhouette to body mass index, both for women and men. Conclusions: These results suggest that the practice of two weekly sessions of resisted exercise for 4 weeks may have a beneficial effect over psychosocial factors and that it is viable and recommended to implement the follow up of these variables in the context of gyms. Besides, the difference between actual silhouette and BMI very much closer at moment T3 suggests that the positive effect of exercise plays an important role over body image. Data found about blood pressure are promising but better understanding is needed. 109930 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Resistance Exercise and Ischemic Preconditioning on Endothelial Dysfunction Caused by Ischemic/Reperfusion Injury in Young Adults and Elderly FABIO TANIL MONTREZOL1, Daniel Bannel2, Helen Jones2, Alessandra Medeiros1, David Low2 (1) Federal University of Sao Paulo; (2) Liverpool John Moores University Ischemic events can cause damage. However, reperfusion can cause more damage. This cluster of injuries are named ischemia/reperfusion injury (IRI). Studies show that short intermittent periods of ischemia can produce beneficial effects, named ischemic preconditioning (IPC), this strategy can reduce the area and injury severity. In humans, IPC have shown reductions on the deleterious effects of an IRI, including in the myocardium. In animal models, previous IPC can preserve systolic function after an IRI. IPC can be applied only remotely (R-IPC) in humans to preserve the myocardium. Then, resistance exercise can be a potential toll to produce such effect. The present study aimed to compare the effects of R-IPC and resistance exercise in lower limbs on the vascular function after a bout of IRI. 13 participants aged 23.61 +- 2.95 (Young group - YG) and 7 participants aged 62.83 +- 2.63 (Elderly group - EG) were evaluated. The protocol was approved by the Liverpool John Moores University (19/SPS/025). Participants showed at the lab in 3 non-consecutive days with interval of at least 72 hours during the morning. The sessions were randomized. Session structure was: participants rested for 20 minutes, then underwent to a brachial artery flow-mediated dilation analysis (FMD), then received the experimental treatment: Control visit rested for 40 minutes, R-IPC visit, cuffs were placed at the medial part of the thighs then inflated for 5 minutes at a pressure of 220 mmHg and deflated for 5 minutes for 4 times, at the Squatting visit performed 5 minutes of squatting without load with cadence of 20 squats per minute and rested for 5 minutes for 4 times. After, for the IRI, a cuff was placed in the humeral midpoint and inflated at 220 mmHg for 15 minutes, after deflation, the reperfusion occurred for 15 minutes. Then, FMD was repeated. 2-factor analysis of variance was performed, p <= 0.05. Results are shown in figure 1. We concluded that IRI can produce temporary vascular dysfunction, such dysfunction can be abolished by R-IPC in young adults and in elderly resistance exercise can abolish deleterious effects of IRI. 109955 Modality: E-Poster Researcher - Non-case Report Category: NURSING Multicenter Registry of Hypertension in Children and Adolescents (Hasca): A Redcap Approach JACQUELINE VAZ ALENCAR1, Emily Justiniano6, Nicole Saldanha de Souza5, Liliana Fortini Cavalheiro Boll1, Luiza Junqueira Trarbach Lovato2, Renata Povoas3, Danielle Dias8, Fernanda Consolim-Colombo4, Katia de Angelis8, Maria Claudia Irigoyen3 (1) Instituto de Cardiologia da Fundacao Universitaria de Cardiologia (IC/FUC) - Porto Alegre, RS - Brasil; (2) University of Technology Sydney (UTS) - Australia, Sidney; (3) Instituto do Coracao da FMUSP (InCor) - Sao Paulo, SP - Brasil; (4) Universidade Nove de Julho (Uninove) - Sao Paulo, SP - Brasil; (5) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) - Porto Alegre, Rio Grande do Sul - Brasil; (6) Hospital de Clinicas de Porto Alegre (HCPA) - Porto Alegre, RS - Brasil; (8) Universidade Federal de Sao Paulo (Unifesp) - Sao Paulo, SP - Brasil Background/Introduction: Hypertension is asymptomatic in childhood and adolescence. We used REDCap to organize the Multicenter Registry of Hypertension in Children and Adolescents (HASCA) survey. Nine Teaching/Health/Research, distributed in different regions, participated in data collection at the national level. Purpose: This study analyzes the national data reported from the REDCap platform and optimizes the obtained results. Methods: This is a Longitudinal observational multicenter study of the registry type using the REDCap platform to implement data from 9 national centers, with children and adolescents aged 7 to 18 years, both genders, from public or private schools, with altered blood pressure indicative of hypertension in any level. On the REDCap platform, the input of the data occurred in different stages: - Screening: form for collecting identification data, anthropometric data, and blood pressure values. - Confirmatory: confirmation of blood pressure values. - Registry: one-year follow-up and systematic data collection. The data were collected electronically and inserted in the REDCap software, a safe methodology. The study follows ethical principles and guidelines for good clinical practice. Results: The HASCA Registry CRF consists of a total of 180 questions. Screening data were collected from July 2018 to December 2019, with 4398 Brazilian children and adolescents, of which 915 had high BP at least twice. Conclusions: It is possible to make a report with HASCA information generated throughout Brazil by Regions, Coordinating Centers, or by Schools to identify where and which children have high blood pressure levels and need to be monitored. 109983 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Application of the Story Drawing in the Research on Spirituality in the Field of Health: Adhesion to the Treatment of Arterial Hypertension and Diabetes Mellitus GILMARA RIBEIRO SANTOS RODRIGUES1, Fernanda Sampaio Novaes2, Gabriella da Cruz Silva Dias2, Claudio Luiz Anunciacao Santos Junior2, Paula Silva Peixoto2, Luciana Feitosa1 (1) Universidade Federal da Bahia; (2) Escola Bahiana de Medicina e Saude Publica Introduction: Spirituality as an object of study of science in the health area is a recent approach. It consists of an individual's strategy to transcend the process of illness, losses and existential emptiness. It is anchored in Brazilian culture and is part of common sense, influencing beliefs, behaviors and worldview. It was considered the assumption that there is a possibility of spirituality influencing the adherence to treatment of people with arterial hypertension and diabetes mellitus. Objectives: To identify whether the representations of people with arterial hypertension and diabetes mellitus about religiosity/spirituality can influence non-adherence to treatment and describe the religious/spiritual practices of these people. Method: Qualitative and quantitative exploratory research, carried out at a philanthropic medical center in the city of Salvador, Bahia, Brazil, in 2019. Participants were individuals over 18 years of age with arterial hypertension and diabetes. Data were collected through semi-structured interviews and the Drawing-Story with Theme procedure. A form consisting of three sections was used, the first with an approach to sociodemographic and clinical characterization data. The second with the guiding questions: (1) How does religiosity/spirituality influence adherence to the treatment of arterial hypertension and diabetes mellitus? (2) What religious/spiritual practices do you use related to DM and AH treatment? (3) What kinds of religious/spiritual practices do you think other people use related to DM and AH? (4) What types of religious/spiritual beliefs can interfere with adherence to treatment for AH and DM? (5) Do you consider that there is any religious/spiritual practice that can contribute to non-adherence to the treatment of AH and DM? And the third contains the guidelines for the design of a themed story. Thematic content analysis was used. Results: The data from the interviews were aggregated into two categories: (1) Spiritual/Religious Practices that Assist in Adherence to Treatment and (2) Treatment Dissociated from Faith. Conclusion: There are several representations about spirituality/religiosity and adherence to the treatment of arterial hypertension and diabetes, however, it is clear that people believe in curing the disease and have hope regardless of the conduct they choose for their treatment. 110030 Modality: E-Poster Researcher - Non-case Report Category: DYSLIPIDEMIA Reference Intervals of Total Cholesterol and Fractions for Brazilian Adults According to the National Health Survey ANA CAROLINA MICHELETTI GOMIDE NOGUEIRA DE SA1, Elton Junio Sady Prates2, Pedro Cisalpino Pinheiro3, Deborah Carvalho Malta1 (1) Graduate Program in Nursing, Federal University of Minas Gerais (UFMG). Belo Horizonte, MG, Brazil; (2) School of Nursing, Federal University of Minas Gerais (UFMG). Belo Horizonte, MG, Brazil; (3) Faculty of Medicine, Federal University of Minas Gerais (UFMG). Belo Horizonte, MG, Brazil Introduction: The reference values of laboratory tests are defined by two threshold classes, the reference intervals (RI) derived from a healthy population and the clinical decision limits, in which a medical decision is recommended. Lipid reference limits were established by clinical studies of cardiovascular outcomes in which clinical decision limits were defined. It should be noted that lipid reference values were collected from studies in developed countries and lipid levels are influenced by demographic, environmental, genetic, ethnic, lifestyle factors and chronic diseases. Therefore, even having defined decision limits, it has been encouraged to build lipid RIs specific to the population that will be applied. However, determining RI is a challenge because it requires methodological rigor, such as a representative sample of the population and care in collection and analysis. In Brazil, international IR are used. The National Health Survey (PNS) carried out laboratory tests, thus, it was possible to establish, in an unprecedented way by non-parametric methodology, RI of total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) for Brazilians. Objective: To estimate RI of TC and fractions for Brazilian adults. Methods: Cross-sectional study, with data from the PNS, between 2014-2015, in 2,976 adults. To establish RI, exclusion criteria were applied (pregnancy; smoking; chronic diseases), outliers were removed (Tukey's method) and partitioned (gender; age; race/color). RI were estimated considering 95% of healthy individuals, the lower limit (LL) corresponded to the 2.5th percentile and the upper limit (UL) to 97.5. Differences were evaluated using the Mann Withney and Kruskal Wallis tests (p <= 0.05). Results: HDL RI (mg/dL) were higher in women (29-74) than in men (25-67). Men had lower TC and LDL RI (mg/dL) between 20 and 39 years (115-239; 51-151) compared to 40 and 59 years (131-250; 57-156) and 60 years or older (125-252; 64-156). Women had higher RI for TC and LDL (mg/dL) at age 60 years or older (128.5-264; 59-172) and for HDL (mg/dL), UL were higher between 40 and 59 years (29-75) than at 20 to 39 years old (29-74) and in white race/color (29-75) compared to brown (29-73). Conclusion: Own lipid RI evidence the health conditions of Brazilian adults and can support the adequate identification of dyslipidemias and prevention of cardiovascular disease. 110043 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES T1 Mapping CMR Imaging Techniques and Their Association with Ventricular Arrhythmias and Sudden Death in Patients in the Early Stage of Chagas Heart Disease MARTHA V T PINHEIRO1, Renata Junqueira Moll-Bernardes1, Gabriel Cordeiro Camargo1, Marcelo Teixeira de Holanda2, Luiz Henrique Conde Sangenis2, Andrea Silvestre de Souza2 (1) ID'Or; (2) FIOCRUZ; (3) Instituto Nacional de Cardiologia Background: Chagas disease involves progressive myocardial inflammation leading to myocardial fibrosis, which may predispose to sudden cardiac death. Although focal fibrosis can be detected by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), this technique is not sensible to detect diffuse interstitial fibrosis. Objectives: The goal of this study was to assess the prognostic value of extracellular volume (ECV) by CMR in predicting ventricular tachycardia (VT) and sudden death in a 4-year follow-up period in Chagas disease. Methods: This prospective cohort study included patients in the early stages of Chagas disease. Myocardial fibrosis assessment by CMR with measurement of ECV was performed. The patients were followed on an outpatient basis and submitted periodically to electrocardiogram and Holter for a period of 4 years. The combined primary outcome was cardiac sudden death, sustained ventricular tachycardia, or cardioverter-defibrillator (ICD) implantation. Results: A total of 47 patients were included; the mean age was 58,6 + 10,4 and 44,7% were male. The ECV maintained an association with the presence of non-sustained VT, a surrogate outcome, even after adjustments for fibrosis mass and left ventricular ejection fraction assessed by CMR. Over the follow-up, 3 patients died suddenly (6,4%) and 2 (4,3%) had sustained VT. These patients had a mean of 45,2 + 21,1 non-sustained VT events (group 1) versus 2,29 + 1,0 (p = 0,001) in the group which not reached the combined endpoint (group 2). In group 1, the mean ECV value was 29,5 + 3,8 and 26,7 + 3,4 (p = 0,04). Conclusion: ECV could be an early marker of increased risk of ventricular arrhythmia in the early stage of Chagas disease, presenting an independent association with NSVT, as a predictor of adverse outcomes. 110045 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Long Term Clinical Outcomes After Implantation of Absorb BVS in a Real World Setting, with Pre Dilatation and Guided by Intravascular Imaging SERGIO GUSTAVO TARBINE1, Costantino R Costantini1, Costantino O Costantini1, Vinicius Shibata1, Marcos Denk1, Rafael Macedo1, Marcio M. Luize1, Everton CArdoso Dombek1 (1) Hospital Cardiologico Costantini Background: The safety and performance of the Absorb Bioresorbable Vascular Scaffold (BVS) has been previously demonstrated with clinical data. However, these trials included patients with simple lesions. The Absorb III trial demonstrated an excess of adverse events following BVS implantation. Aiming to evaluate clinical outcomes, we analyzed the treatment of real world patients using optimal technique and intravascular image guidance in all cases, at long term follow up from a single center. Methods: Observational retrospective study, in a single Brazilian center, from 12/2014 to 12/2017, including 128 patients treated with BVS implantation. Safety and efficacy outcomes were analyzed in the in-hospital and late follow-up (5 years). Results: All 128 patients completed 4 years 3 months follow-up. Mean age was 58,2 years, 85,9% of the patients were men, and 28,1% were diabetic. Regarding clinical presentation, 54,6% had stable angina or silent ischemia. Intravascular imaging (IVUS-OCT) was used in all cases. Lesion preparation included balloon PTCA, and when necessary Cutting balloon and PTCRA. Device success was achieved in 100% of cases with 99,2% overall procedure success rate (1 case of sub acute thrombosis). Long term major adverse cardiovascular events rate were (including hospital stage): Cardiac death 1,5%, acute stent thrombosis 0,78%, MI 2,34%,TVR 16,4%. Conclusions: The analysis of this cohort of pts, in a real world setting with more complex scenarios, showed so far to be safe and effective at late follow-up using an enhanced technique, including intravascular imaging in all cases. Wether these results are durable beyond 5 years will be reported. Keywords: Percutaneous Coronary Intervention, Absorbable Implants/utilization, Everolimus, Coronary Artery Disease, Clinical Evolution. 110059 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Acute Myocardial Infarction Care Program and Its Impact on Mortality in the Public Health Network ANA KAROLINA QUEIROZ DE SOUZA RICARDO1, Natanael Barbosa dos Santos3, Sara Carolline Gomes de Araujo Lima2, Patricia Caldas de Oliveira1, Eliel Bezerra da Silva Junior1, Antonio Fernando Barros Pereira Junior4, Isabela de Angelles Floro Alonso1, Andre Arthur de Souza Lima3, Marcelo Menezes Malta1, Bibiana Toshie Oniki de Mendonca2, Monteiro Pires Bastos Junior3 (1) Hospital do Coracao de Alagoas; (2) Centro Universitario Tiradentes de Alagoas; (3) Centro Universitario Cesmac; (4) Universidade Estadual de Ciencias da Saude de Alagoas Introduction: Cardiovascular diseases are important causes of morbidity and mortality worldwide. In 2019, in Brazil, 95,557 deaths were due to acute myocardial infarction, the main etiology. Treatment systems in STEMI aim to improve care and survival; there is a lack of data on their performance. Objective: To evaluate the impact of the institution of a STEMI care program on mortality in the public health network of Alagoas. Methods: Observational, analytical and cross-sectional study, authorized by the CEP (opinion No. 3,283,780), data tabulated between January 2017 and June 2019, analyzed using the Mann-Kendall test, comparison of factors by regression and multiple logistic regression. Census sample of 712 participants. Results: The mean age was 64.3 (+-13.1) years and 58.3% were men and 31.3% of the sample was treated; the main cause of non-treatment was symptomatology >12h in 43.5% of the untreated. The prevalence of risk factors (RF) was: 68.3% hypertensive, 36.5% diabetic and 29.4% smokers. The in-hospital death rate was 5.6%. Temporal trends were observed for treated and untreated groups: at time 1, increasing trend for both treated (p < 0.001) and untreated (p = 0.04); while at time 2, there was no increasing or decreasing trend (p > 0.05); at time 3, there is an increasing trend (p < 0.001) for both groups. At time 4, for treated patients, there is a significant decreasing propensity (p = 0.02). Time 5 reinforces a decreasing trend (p = 0.008). Times 6 and 7, no trend was observed. However, at time 8, there is a decreasing trend in the treated group (p = 0.009). At time 9, there is a significant drop in time (p = 0.003). Conclusion: It is evident that the care network is viable and allows better access to STEMI treatment. Hospital mortality was similar to systems in developed countries. There is a need for population education revealed by the significant increasing trend of pre-hospital time. There was an improvement in care for the treatment of STEMI, demonstrated by the significant downward trend at times 4, 5 and 8. In addition, the data contribute to helping the construction of public health policies, as well as guiding prevention strategies, especially for those with RF. 110062 Modality: E-Poster Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Pulse Wave Velocity Response from Renal Denervation - A Systematic Review LILIAN SOARES DA COSTA1, Valerio Fuks4, Maria gabriela Pimenta dos Santos2, Julia Resende de Oliveira2, David Ferreira de Lima Duarte2, Antonio Carlos Eberienos Assad Filho2, Gabriela Gama Zagni Jardim3, Paola Pugian Jardim4, Andrea Vaospasse Cocco Faria4 (1) Universidade Estacio de Sa/IDOMED, Campus Citta e Presidente Vargas e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (2) Universidade Estacio de Sa/IDOMED, Campus Citta; (3) Universidade Estacio de Sa/IDOMED, Campus Vista Carioca; (4) Instituto Estadual de Cardiologia Aloysio de Castro/IECAC Introduction: Renal denervation (RDN) has been shown to be effective in reducing BP in treatment-resistant hypertension. Ambulatory blood pressure (ABPM) and central blood pressure (BP) are better predictors for overall cardiovascular risk and mortality than brachial BP. Renal denervation (RDN) has been shown to reduce these pressure parameters, but data on central ambulatory BP and arterial stiffness (AS) analysis after RDN are limited and have to be highlighted. Objective: A systematic review on the role of arterial stiffness (AS) in renal denervation (RDN) treated-resistant hypertensive. Methods: PubMed and Scielo databases, using the descriptors "denervation" AND "hypertension" AND "pulse wave velocity". Twenty-two citations were identified and being considered. Results: Some studies sought to investigate the effect of RDN in patients with treatment-resistant hypertension according to the established definition and confirmed by 24-h ABPM. These data indicate that RDN may reduce office and 24-h ABPM substantially in patients with moderate treatment-resistant hypertension. Central ambulatory BP is reduced and ambulatory assessed averaged daytime pulse wave velocity (PWV) improved after RDN and total vascular resistance decreased. Multivariate analysis showed that short-term effects on PWV were BP-related, whereas during 6 months follow-up, improvement of PWV becomes BP-unrelated. RDN improves peripheral and central blood pressure as well as AS and, thus, may improve cardiovascular outcome. The BP changes were associated with reductions in peripheral resistance, whereas cardiac output, plasma renin, aldosterone levels and renal function remained unchanged. The observed effects were not explained by an increased intake of antihypertensive medications. RDN did not result in a statistical significant effect on end organ damage 12 months after treatment. The statment that the arterial stiffness beneficial was observed during follw-up, assumed the supposition that an improvement of arterial mechanical properties coul be related to a reduced sympathetic arterial drive. Conclusion: Extended assessment of AS can help improve patient preselection for renal sympathetic denervation and identify which subgroup of hypertension patients will benefit by sympathetic modulation. RDN improves brachial and central ambulatory BP, arterial stiffness, and total vascular resistance, indicating an improvement of cardiovascular outcome. 111669 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Potential Risk of Early Hospital Discharge After Acute Coronary Syndromes: Observations from Secure-Pci Trial and Accept Registry PEDRO GABRIEL MELO DE BARROS E SILVA1, Otavio Berwanger2, Renato Nakagawa1, Thiago Macedo3, Lucas Tramujas1, Dalton Precoma4, Oscar Dutra5, John H Alexander6, Christopher B Granger6, Renato D. Lopes3 (1) HCor Research Institute, Sao Paulo, Brazil; (2) Hospital Israelita Albert Einstein, Sao Paulo, Brazil; (3) Brazilian Clinical Research Institute, Sao Paulo, Brazil; (4) Pontificia Universidade Catolica do Parana, Curitiba, Brazil; (5) Instituto de Cardiologia Fundacao Universitaria de Cardiologia do Rio Grande do Sul, Porto Alegre, Brazil; (6) Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Background: In clinical practice, there is large variability in hospital length of stay among cases of acute coronary syndrome (ACS). Even in ACS patients without major complications, the ideal timing for hospital discharge is unknown. Objective: To assess the risk of clinical outcomes within 30 days among patients who did not have a major cardiovascular complication in the first 48 hours after the onset ACS. Methods: SECURE PCI trial and ACCEPT registry enrolled patients admitted with ACS (with or without ST elevation). Patients who had a major cardiovascular event (MACE) within 48 hours were excluded from this analysis since these patients would not have been considered eligible for an early discharge. The rate of MACE between 48 hours and 30 days was described in the overall population and according to the type of ACS and timing of PCI. MACE was defined as myocardial infarction, stroke or death. Multivariable analysis was used to identify factors associated with clinical outcomes. The cases of MACE between 48h and 30 days in the SECURE-PCI trial were further evaluated by source documents and classified according to clinical stability before the occurrence of the events in order to identify patients that indeed would be potentially eligible for early discharge in clinical practice. Results: From the 9,244 patients enrolled in the both studies, we did analyze 8,684 (93.9%) patients who had a confirmed ACS and did not have a MACE within 48 hours. At 30 days, the rate of MACE was 4.1% varying from 2.4 to 4.8% according to type of ACS. In the multivariate analysis, the following variables were associated with the risk of MACE: Age (HR 1.25 per 10 years increment; P < 0.01); Diabetes (HR 1.44; P = 0.02); Type of ACS (STEMI HR 3.56; P < 0.01; NSTEMI HR 1.68; P = 0.049) and PCI within 24 hours (HR 0.36; P < 0.01). The overall rate of death at 30 days was 2.4% but was 0.9% among patients who underwent PCI within 24 hours and were stable in the first 48 hours. Conclusion: Patients with ACS undergoing PCI in the first 24 hours who are stable in the first 48 hours after hospital admission presented low risk of MACE in 30 days (mortality <1%). Advanced age, Diabetes, STEMI and PCI after 24 hours were associated with worse 30-day outcomes among patients without MACE after 48 hours of hospitalization due to ACS. Our findings suggest that early discharge of patients around 48 hours seems safe and reasonable and might save costs and resources utilization. 110086 Modality: E-Poster Researcher - Non-case Report Category: NURSING Effect of Motivational Interview on the Self-Care of Patients with Heart Failure: A Randomized Clinical Trial PAULA VANESSA PECLAT FLORES1, Paula Vanessa Peclat Flores1, Ana Carla Dantas Cavalcanti1, Lyvia da Silva Figueiredo1 (1) Universidade Federal Fluminense - UFF Introduction: Heart Failure is a complex syndrome that demands strict commitment to the therapeutic regimen. In addition to the monitoring strategies that will be used, to achieve better results it is vital to motivate the patient to incorporate new habits into the routine of daily life. Objective: To analyze the effectiveness of the motivational interview in the self-care of patients with chronic heart failure. Method: A randomized, multicenter clinical trial where the intervention group and the control group were followed for 60 days in each of the centers. A total of 130 patients were included, where the intervention group received 3 appointments per motivational interview, with a 30-day interval, while the control group maintained the conventional follow-up in the clinics they attend. The data were evaluated through the Self Care Heart Failure Index 6.2, before and after the intervention, in each of the centers. Among the several statistical calculations performed, the use of mean, median, simple frequency, chi-square, t-test, mann whitney and wilcoxon is highlighted and the effect of the intervention was calculated by Cohen's d. Results: The global sample (Brazil + Uruguay) has 118 patients, 59 in the control group and 59 in the intervention group. Self-care, evaluated through the sub-scales of maintenance, management and confidence, presented Cohen's d 0.6723 and p-value (<0.001), indicating medium and significant effect; d of Cohen 0.5086 and p-value (0.187), which means a medium effect but not significant; d of Cohen 0.9877 and p-value (<0.001), showing a high intervention effect with significance. Conclusion: Data from these studies showed that motivational interviewing is effective in self-care of patients with chronic heart failure. Motivational interviewing is a low-cost, effective approach that can be applied by trained professionals who work clinically with patients with heart failure. 110122 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION A Prospective Study on Adherence to Secondary Prophylaxis for Rheumatic Fever using Benzathine Penicillin G in Mozambique ZAKIR OSSMAN1, Edna Lichucha1, Alcides Munguambe1, Lucio Ribeiro1, Karen Sliwa3, Albertino Damasceno2, Ana Olga Mocumbi1 (1) Instituto Nacional de Saude - INS; (2) Nucleo de Investigacao, Departamento de Medicina, Hospital Central de Maputo, Mozambique; (3) Cape Heart Institute, University of Cape Town Introduction: Delivery of regular long-acting intramuscular benzathine penicillin G (BPG) injections is the most effective method for secondary prophylaxis to prevent recurrence of acute rheumatic fever (ARF). Objective: We aimed to assess the adherence rates to BPG regimens for prevention of ARF in a low-income setting. Methods: Between November/2017 and October/2018 we profiled a cohort of patients with RHD on secondary prophylaxis at two hospitals in Mozambique; then we prospectively assessed adherence to secondary prophylaxis using monthly BPG injections. Cultures obtained from throat swabs collected at the 12th month of prophylaxis on 78 patients selected randomly, and were examined by gram stain, catalase test and CAMP test to detect Group A Streptococcus. Results and Discussion: We enrolled 121 patients, mostly adolescents (mean age 20.8 years; SD 5.9) and females (77; 63.6%). Isolated or combined mitral regurgitation was the commonest lesion (107 patients; 88.4%), followed by aortic regurgitation (54; 44.6%) and mitral stenosis (21; 17.4%). The mean follow up was 19 months. The adherence rate was 86.8%, corresponding to 2228 injections applied out of the 2555 expected; only 1708 (66.8%) were administered at the expected date and 59 patients (49%) were fully compliant. Testing for GAS throat colonization in patients randomly selected on month 12 was negative. One fatal event occurred in relation to BPG injection, not fulfilling criteria for anaphylaxis. Conclusions: RHD patients on secondary prophylaxis in urban hospitals in Mozambique had good adherence and acceptable compliance to monthly BPG injections. The incidence of ARF during follow-up was low and no classic anaphylaxis occurred. Further research is warranted to address gaps in delivery of secondary prophylaxis. 110435 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Relationships between Brachial-Ankle Pulse Wave Velocity and Left Ventricular Longitudinal Strain Three Months After COVID-19 Pneumonia YAROSLAVSKAYA E.I.1, Migacheva A.V.1, Krinochkin D.V.1, Shirokov N.E.1, Gorbatenko E.A.1, Korovina I.O.1, Osokina N.A.1 (1) Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences Introduction: Data regarding the influence of arterial stiffness on longitudinal myocardial strain has been scarce. This is especially important for patients who have undergone a complicated course of COVID-19. Objective: To investigate the associations between brachial-ankle pulse wave velocity (baPWV) and left ventricular (LV) longitudinal strain 3 months after COVID-19 pneumonia. Methods: 369 patients (52 +- 11 (from 19 to 84) years; 50.9% women) 3 months +- 3 weeks after discharge after COVID-19 pneumonia were prospectively enrolled into the study. All participants underwent conventional echocardiography, including 2D speckle-tracking echocardiography. Measurements of baPWV were made at the same day as echocardiography in 322 patients. Parameters of LV global longitudinal strain (LV GLS) and segmental longitudinal strain were studied in 296 patients with optimal visualization quality in echocardiography. Both baPWV and LV longitudinal strain were measured in 243 patients. Results: Three months after discharge, obesity was noted in 46.5% of patients, cardiovascular diseases were diagnosed in 73.4%. Arterial hypertension occurred in 71.5% of patients, coronary artery disease - in 22.5%. The median baPWV were 13.3 [11.8; 15.1] cm/s and 13.4 [11.9; 15.1] cm/s for the left and right sides, respectively. Mean LV ejection fraction was 67.8 +- 5.0%, mean LV GLS was -19.6 +- 2.5%. The baPWV showed a weak correlation with longitudinal strain of LV basal level (r = 0.289 for the right side and r = 0.272 for the left side, both p < 0.001) and of LV mid level (r = 0.229, p < 0.001 for the right side and r = 0.218 for the left side, p = 0.001). The baPWV showed a correlation of medium strength only with the longitudinal strain of LV basal anterior segment (r = 0.303 for the right side and r = 0.309 for the left side, both p < 0.001). There were no correlations between baPWV and strain of LV apical level segments. Conclusion: In patients after COVID-19 pneumonia 3 months after discharge baPWV increase associated with deterioration of LV longitudinal strain at basal and mid levels, more pronounced in LV basal anterior segment. 110457 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Adherence to the Acute Coronary Syndrome Care Guidelines: A Program of the Best Practice in Cardiology LUIZ GUILHERME PASSAGLIA1, Luiz Guilherme Passaglia1, Carolina Teixeira Cunha Erika1, Erika Nunes de Oliveira Rodrigues1, Flavia Mariana Mendes Diniz1, Darkiane Fernandes Ferreira1, Tiago Almeida de Oliveira2, Maria Augusta Duarte Abreu2, Regina Bicalho Gomes de Faria2, Pedro Henrique Coelho Pinto2, Antonio Luiz Pinho Ribeiro2 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG - Brasil; (2) Faculdade De Medicina da Universidade Federal de Minas Gerais (UFMG) Introduction: In Brazil, low adherence to care guidelines is one of the reasons for the high mortality from acute coronary syndrome (ACS). In view of this, the Brazilian Society of Cardiology (SBC) in partnership with the American Heart Association and with the support of the Ministry of Health developed the Best Practices in Cardiology Program (BPC Program), whose objective is to evaluate the rates of adherence to the SBC guidelines for in institutions of the Unified Health System before and after the implementation of the project. Method: Prospective observational study with data collection from May 2016 to December 2021. The performance measures analyzed were drugs prescribed at hospital discharge. The primary outcome of the study consisted of the evaluation of performance measures with a minimum stipulated target of 85% of global adherence. Results: In this sample, 932 patients were included, with a mean age of 61.6 +- 12.1 years, 69.2% of whom were male, with a low level of education (77.1% with incomplete secondary education or less) and low family income (91.5% with <=5 minimum wages a month). The main comorbidities were current or previous smoking (67.1%), arterial hypertension (65.7%), diabetes (29.7%), and dyslipidemia (23.0%). In the characterization of ACS, ST-segment elevation infarction corresponded to 68.3%, with Killip classification <=2 in 75.5% of the sample. Most of the patients (92.2%) underwent coronary angiography, which showed the following pattern of coronary disease: 24.1% trivascular, 16.9% bivascular, 17.5% univascular, with the anterior descending artery being affected in 21.8% of the cases. Coronary angioplasty of the culprit's vessel was performed in 64.9% of the cases, and only 5.4% of the sample was referred to coronary artery bypass graft surgery. Analysis of performance measures showed aspirin (98.5%), beta-blockers (94.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (96.3%) and statins (96.6%) at hospital discharge. There were 27 deaths during hospitalization (2.9%). Discussion: The predominance of males, age >= 50 years, and high prevalence of comorbidities show characteristics of ACS patients already known by epidemiological data extensively published in the medical literature. Performance measures indicate good adherence to ACS care guidelines in the hospital. Conclusion: Adherence to quality programs such as the BPC Program is an essential step in improving care for patients with ACS. 110441 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION The Extreme Prognosis Value of Cardiopulmonary Exercise Testing in Heart Failure DIANE XAVIER DE AVILA1, Ricardo Vivacqua Cardoso Costa2, Salvador Manoel Serra3, Marcelo Westerlund Montera2, Evandro Tinoco Mesquita1, Alexandre Siciliano Colafranceschi2 (1) Complexo Hospitalar de Niteroi; (2) Hospital Pro-Cardiaco; (3) Instituto Estadual de Cardiologia Aloysio de Castro Introduction: Cardiopulmonary exercise testing (CPET) is a well-established clinical tool to predict outcome, stratifying cardiovascular risk and help to select candidates for heart transplantation (HTx) or left ventricular assist devices (LVAD) in patients with chronic heart failure (CHF). Purpose: To evaluate CPET measurements in advanced CHF patients that are being considered for HTx or LVAD and its association to early mortality regardless of the performed procedure. Methods: Maximum intensity CPET was performed on a treadmill and ramp protocol in 73 patients with CHF and reduced ejection fraction, NYHA functional classes III and IV between 2012 and 2021. Measurements derived from CPET were the following: peak V'O2, V'O2 at the anaerobic threshold (AT), percentage of the V'O2 of the anaerobic threshold in relation to the peak, the slope of oxygen consumption efficiency (OUES), Oxygen uptake efficiency plateau (OUEP), VE/VCO2 slope, maximum heart rate (HR), circulatory power (CP), and the relation (VE/VCO2 slope)/(VO2peak). Results: Seventy-three patients, 75% males. Mean age of 70 +- 9 years. Almost half (47%) had ischemic etiology. There were no complications related to CPET. Ten patients were transplanted, six had an intracorporeal LVAD implanted and the reminder (57 patients) were kept in supervised physical rehabilitation program. There were 12 deaths, 2 in HTx, 2 in LVAD, 8 in the rehabilitation group. Mean follow-up among the survivors was 43 months +- 40,6 and it was 12,1 +- 10,3 months in those who died. CPET derived measurements between survivors and non-survivors, respectively, were as follows: V'O2 peak (mL.kg-1.min-1): 12,6 +- 4,6 and 8,5 +- 2,8 (p = 0,001); the V'O2 AT (mL.kg-1.min-1): 9,8 +- 3,3 and 6,0 +- 3,0 (p = 0,0004); VE/VCO2 slope: 34,2 +- 12,1 and 67,3 +- 65,6 (p = 0,0002); R peak: 1,1 +- 0,2 and 1,0 +- 0,1 (p = 0,009); T1/2, in seconds: 136,1 +- 47,8 and 167,9 +- 78,5 (p = 0,03); HR reduction at the first minute 16,7 +- 13 and 7,2 +- 5 (p = 0,009); OUES (L.min-1): 1,2 +- 0,4 and 1,0 +- 0,3 (p = 0,104) and CP [(ml O2.kg-1.min-1).mmHg] 1.530 +- 671,6 and 960,6 +- 363,6 (p = 0.005), OUEP (ML/L): 34,2 +- 8,3 and 25,1 +- 8,3 (p = 0.001) and the relation VE/VCO2 slope and V'O2 peak were 3,1 +- 2,0 e 11,4 +- 19,5 (p = 0.001). Conclusion: The predisposition to early death could be stratified by V'O2 peak, V'O2 AT, VE/VCO2 slope, T1/2, recovery HR, CP, the relation VE/VCO2 slope)/(V'O2 peak) and notably, OUEP can be more one powerful predictor for early intervention due to its association with severity. 110448 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The use of Laboratory and Instrumental Parameters for Prediction of Long-Term Events in Patients with Cardiovascular Pathology and Type 2 Diabetes Mellitus who Underwent COVID-19 Associated Pneumonia PETELINA T.I.1, Musikhina N.A.1, Garanina V.D.1, Avdeeva K.S.1, Sharoyan Y.A.1, Gapon L.I.1, Yaroslavskaya E.I.1 (1) Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences Introduction: By given pandemic status, the viral infection has shown how SARS-CoV-2 can affect patients involved in other noninfectious epidemics that have been gaining momentum for years. Objectives: To perform a prospective analysis of blood biomarkers in patients with cardiovascular (CV) diseases (CVD) who underwent COVID-19 associated pneumonia with and without type 2 diabetes mellitus (DM2); to assess the nature of their relationship with instrumental parameters and to identify indicators of long-term adverse CV events. Methods: Out of 380 patients with SARS-CoV-2 associated pneumonia participating in the study, we used data of 65 patients. They were divided into 2 groups: group 1 included patients with CVD: arterial hypertension (AH) in combination with coronary artery disease (CAD) without DM2 (n = 45), group 2 - patients with CVD and DM2 (n = 20). Patients were examined at baseline and 3 months after discharge. We evaluated parameters of general blood test; biochemical parameters; instrumental parameters - ABPM, PWV in right and left elastic arteries, echocardiography with the study of left ventricular (LV) apical myocardial strain, computer tomography of lungs. Results: The analyzed leukocyte parameters and their index coefficients - increase in neutrophils/lymphocytes ratio and decrease in lymphocytes/CRP ratio were more significantly changed in DM2 group. Patients in both groups had a significant excess of baseline max CRP concentrations with decrease in parameters after 3 months, but with persistent excess values in group 2 (p < 0.0011). 3 months after discharge patients with DM2 had levels of hs-CRP, IL-1b and TNFa (p < 0.05) that exceeded both the reference values and those in group 1, which reflected the presence of more pronounced vascular inflammatory potential for possible adverse events in this group of patients in post-COVID period. In addition, the exceeding values of NT-proBNP, SBP and DBP 24, PWV-L and apical LV myocardial strain in group 2 compared to group 1 may be indicators of occurrence and progression of adverse CV events in patients with DM2. Conclusions: In groups of patients with AH and CAD, which differ only by the presence of DM2, it is clearly seen that comorbid condition can significantly affect the development of adverse CV complications due to increased inflammatory potential of blood parameters, increased stiffness of the vascular wall, and the presence of myocardial longitudinal strain of LV apical segments. 110901 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Virtual Cardiac Rehabilitation Post Coronary Artery Bypass Graft (CABG) - Real World Experience from India ALBEN SIGAMANI1, PALLAV SINGH1, NUMEN CARE TEAM1 (1) NUMEN HEALTH Coronary Artery Disease (CAD) is the number one killer of cardiovascular diseases; yearly, nine-million deaths. CABG was first done in India in 1975; the surgery has grown exponentially, to nearly 100,000 every year. Ischemic cardiomyopathy (IC) and delays in undergoing an evidence-based recommended CABG contribute to significant mortality and morbidity over five years of survival (>35% composite event rate). Cardiac rehabilitation, an evidence-based, effective secondary prevention, is scarce in India; there is just one seat for every 30,000 new IC patients. Numen health is an online digital health platform that organizes virtual cardiac rehabilitation. The program is delivered at the patient's home via a mobile application. Referrals are received from cardiologists and cardiac surgeons at the time of discharge following a coronary artery event or procedure. On establishing contact and intent to perform cardiac rehabilitation, the patient is subjected to several online tele assessment sessions to help the patient and the care team arrive at a baseline of their health status. The discharge summary of their most recent admission is used for setting Specific Measurable, Achievable, Relevant, and Timely (SMART) Goals. All patients are categorized as per age, gender, known history of pre-existing chronic diseases, medication consumption pattern, physical activity input, potential energy output, detailed analysis of the daily diet, habits, and identification of possible nutritional deficiencies. The program is subscription-based, and the fee is collected either monthly. Between February 2021 and April 2022, 83 patients post CABG have been referred to the program. This represents 10% of the overall number of patients who participated in the program and were referred from 15 cities and 33 doctors across India. They spent a median of 90 days (ranging between 30 to 210 days) on the program and had 600 interactive sessions with the assigned health care manager and other health experts. The age was between 38 and 72 years; 53 (64%) were males. 35(42%) had baseline type 2 diabetes, 8(10%) had significant comorbidity. There were zero deaths, and 35(42%) had achieved their assigned goals. Digital health can bridge the widening gap of providing cardiac rehabilitation to the growing prevalence of IC in India. Virtual cardiac rehabilitation effectively delivers comprehensive secondary prevention to patients post CABG and any coronary event or intervention. 110458 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Adherence to the Assistance Guidelines for Heart Failure: A Program of the Best Practice in Cardiology LUIZ GUILHERME PASSAGLIA1, Luiz Guilherme Passaaglia1, Carolina Teixeira Cunha Erika1, Erika Nunes de Oliveira Rodrigues1, Flavia Mariana Mendes Diniz1, Darkiane Fernandes Ferreira1, Tiago Almeida de Oliveira2, Maria Augusta Duarte Abreu2, Regina Bicalho Gomes de Faria2, Pedro Henrique Coelho Pinto2, Antonio Luiz Pinho Ribeiro2 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG - Brasil; (2) Faculdade De Medicina da Universidade Federal de Minas Gerais (UFMG) Introduction: In Brazil, low adherence to guidelines is one of the reasons for the high mortality from heart failure (HF). In view of this, the Brazilian Society of Cardiology (SBC) in partnership with the American Heart Association, and with the support of the Ministry of Health, implemented the Best Practices in Cardiology Program (BPC Program), whose objective is to evaluate the rates of adherence to the SBC guidelines in institutions of the Unified Health System before and after the implementation of the project. Method: Prospective observational study with data collection from May 2016 to December 2021. The performance measures analyzed were the medications prescribed at hospital discharge and the scheduling of a return appointment. The primary outcome of the study consisted of the evaluation of performance measures with a minimum stipulated target of 85% of global adherence. Results: In this sample, 431 patients were included. The mean age was 59.0 +- 14.6 years, 55.0% were men and 85.4% had a previous diagnosis of HF. The main comorbidities were arterial hypertension (43.4%), atrial fibrillation/flutter (41.1%), diabetes (26.0%), acute myocardial infarction (16.2%), and hypothyroidism (16.0%), with a high rate of current and/or previous smoking (51.0%). The main etiology of HF was Chagas (25.7%), followed by idiopathic (23.0%), ischemic (22.3%), and valvular disease (15.3%). The predominant hemodynamic profile was wet and warm (67.4%), followed by wet and cold (25.0%). At admission, 61 (14.2%) patients underwent heart transplantation. The mean left ventricle ejection fraction was 35.9% (+-17.0), and 83 (19.3%) patients died during hospitalization. The analysis of performance measures showed a return appointment schedule (94.6%), beta-blocker (94.8%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (97.3%), and spironolactone (80.9%) at hospital discharge. Discussion: The clinical characteristics of patients with a high prevalence of comorbidities reflect the profile and complexity of patients hospitalized at the hospital and highlight the need for multidisciplinary care. The values of the performance measures indicate good adherence to HF care guidelines, except for the prescription of spironolactone at hospital discharge. Conclusion: Adherence to quality programs such as the BPC Program is an essential step in improving care for patients with HF. 110472 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Relationship between Urinary Norepinephrine, Fibrosis and Arrhythmias in Chronic Chagas Heart Disease with Preserved or Mildly Reduced Ejection Fraction EDUARDO MARINHO TASSI1, Emilia Matos do Nascimento1, Marcelo Abramoff Continentino1, Basilio de Braganca Pereira1, Roberto Coury Pedrosa1 (1) Universidade Federal do Rio de Janeiro (UFRJ) In Chronic Chagas Cardiomyopathy (CCC), studies are needed to identify arrhythmogenic risk factors in patients where moderate to severe ventricular dysfunction is not present. The direct relationship between sympathetic neural activity and norepinephrine is known. In patients with heart failure, sympathetic hyperactivity is persistent. However, in CCC, there are indicators that the sympathetic system is heading towards exhaustion as cardiac involvement progresses. Objectives: To verify the dependence between frequent ventricular extrasystoles (FVE), left ventricular ejection fraction (LVEF), extension of fibrosis by cardiac magnetic resonance (CMR) and urinary norepinephrine (NOREPI) measurement in CCC with preserved or minimally compromised LVEF. Methods: The presence of ventricular extrasystoles >720 in 24h was analyzed on Holter. In CMR, the biventricular ejection fraction, presence of segmental alteration and detection and quantification of fibrosis mass using the delayed enhancement technique were evaluated. NOREPI was measured using the Muskiet method. The correlation coefficient matrix was calculated to measure the predictive ability of the variables to predict another, with a significant p-value of p < 0.05. A total of 59 patients were included. Mean age was 57.9 + 10.94 years. FVE was detected in 28 patients. The variable fibrosis showed a negative correlation with the LVEF found (R of -0.61) and with NOREPI (R of -0.68), as well as the variable FVE showed a weak negative correlation with the LVEF (R of -0.33) and to NOREPI (R of -0.27). LVEF, on the other hand, showed a positive correlation with NOREPI (R of 0.83). The variables fibrosis, LVEF and NOREPI showed a high power of association with each other according to Cramer's V statistics (fibrosis and NOREPI 0.64, LVEF and NOREPI 0.63 and fibrosis and LVEF 0.53). Conclusion: In patients with CCC with preserved or slightly reduced ejection fraction, it is confirmed that the arrhythmogenic substrate is already present in this population, with dependence between NOREPI levels, LVEF and myocardial fibrosis, but not with the presence of FVE (>720 in 24h). 112420 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Customized Expandable Polyurethane Stent Valve, Implanted by Catheter. Strategies for Pulmonary Artery Approach MIGUEL MALUF1, Miguel Angel Maluf1, Alfredo Eyer Rodrigues1, Maria Eduarda Siqueira1, Ana Fatima Salles1 (1) Universidade Federal de Sao Paulo; (2) Hospital Alemao Oswaldo Cruz - SP Background: Patients with tetralogy of Fallot, undergoing Right Ventricular Remodeling, in childhood, with or without pulmonary valve reconstruction, evolve, in the late follow-up, with pulmonary insufficiency and Right Ventricular dysfunction, requiring the implantation of a pulmonary prosthesis. The anatomical variations of the pulmonary artery, associated with the presence of calcifications, dilations, or stenosis as a result of surgeries performed, require adequate planning in the surgical approach for Transcatheter Pulmonary Valve Replacement - TPVR. Material: A new Expandable Polyurethane Stent Valve, implanted by catheter, in pulmonary position has been developed and approved in Biocompatibility, Physical, Hydrodynamic, Fatigue, Experimental, and Ultrastructure Study of explanted sheep prostheses after 24 months of follow-up, analysis, following ISO 5840-3, 2015. Method: In a group of 45 adult patients, in the late follow-up of surgical correction of Tetralogy of Fallot, with late follow-up, at Sao Paulo Federal University, with an indication for TPVR, they were classified into 6 groups according to the anatomical aspects of the pulmonary artery, analyzed by CT Angiography and scheduled minimally invasive procedure intervention, TPVR: Tipe.1: Pulmonary Valve Insufficiency (PVI) Tipe.2: PVI + Pulmonary Trunk (PT) stenosis Tipe.3: PVI + PT aneurysmal dilation Tipe.4: PVI + PT + Right Pulmonary Artery (RPA) + Left PA (LPA) stenosis Tipe.5: Pulmonary prosthesis dysfunction Tipe.6: Valved Conduit (VC) disfunction Through post-processing images by CT Angiography, it was possible to enlarge them to their natural size, followed by 3D printing, inelastic and transparent plastic mass, keeping the interior of the hollow cardiac cavities. Custom prosthesis manufacturing: 3 transverse diameters (TD) are measured: TD1: At the level of the Pulmonary Ring; TD2: In the middle third of the TP and TD3: At the level of the origin of the RPA and LPA. Also, a longitudinal measure (LM), allows for knowing the length of the prosthesis. Conclusion: The strategy for the treatment of residual defects, after correction of the Tetralogy of Fallot, is based on the need to have customized devices to obtain successful and lasting results. 110529 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Evaluation of Cardiac Fibrosis using T1 Mapping and Cardiovascular Risk in Patients with Non-Alcoholic Fatty Liver Disease FLAVIA VERNIN DE OLIVEIRA1, Gabriel Cordeiro Camargo1, Martha Valerio Tavares Pinheiro1, Adriana Soares Xavier de Brito1, Renee Sarmento de Oliveira1, Daniella Braz Parente1, Renata de Mello Perez1, Rosana Souza Rodrigues1, Ana Maria Pitella de Souza Leite1, Gilberto Portela1, Andrea Silvestre de Sousa1, Renata Junqueira Moll Bernardes1 (1) INSTITUTO D'OR DE PESQUISA Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the principal cause of chronic hepatic disease in developed countries, reaching almost 30% of the adult population. It has a large spectrum of histological presentation, from steatosis to cirrhosis. It is a multisystemic disease, affecting a variety of organs, including heart and vascular system, and these are the principal cause of death for these patients, beyond the hepatic disease. Interstitial fibrosis is a factor of worse prognosis for heart and liver, individually, but the correlation between cardiac fibrosis and liver fibrosis has not been studied yet. Purpose: To define the frequency and grade of early myocardial fibrosis in patients with NAFLD and correlate with the intensity of hepatic fibrosis. Methods: Forty-four patients with NAFLD were included; prospectively, the patients performed echocardiogram, myo-intimal carotid measurement by ultrasound, coronary calcium score by computed tomography, cardiac and hepatic magnetic resonance imaging using elastography and T1 mapping sequences; twenty-eight were allocated in the group without fibrosis or with discrete hepatic fibrosis (Group 1) and sixteen patients with significant hepatic fibrosis in Group 2, defined by the magnetic hepatic elastography. Results: The mean age was 57.9 years and 59% were women. The group with significant hepatic fibrosis had also more cardiac interstitial fibrosis, compared with Group 1. The median of myocardial ECV for Group 1 was 22.7% and for Group 2 was 26%, with p = 0.002. The correlation between hepatic and cardiac fibrosis was 0.45, with p = 0.02, even when adjusted for age and body mass index. We also found a negative correlation between hepatic fibrosis and the Global Longitudinal Strain of the left ventricle (r = -0.36 and p 0.016) and with the volume of the left atrium (r = 0.30 and p = 0.04). Conclusion: The study suggests the presence of a correlation between hepatic fibrosis in patients with NAFLD and the presence of diffuse interstitial myocardial fibrosis detected by the cardiac T1 mapping magnetic resonance. 110556 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Factors Associated with Improvement of Left Ventricular Function After Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure: A Multicenter Experience MARCOS ROBERTO QUEIROZ FRANCA1, Andre Assis Lopes do Carmo1, Gustavo de Araujo Silva1, Andre Dias Nassar Naback1, Reynaldo de Castro Miranda2, Anna Terra Franca3, Henrique Barroso Moreira2, Vitor Freitas Fontes1, Leandro Garambone de Cerqueira1, Lucas Ruback1, Antonio Luiz Pinho Ribeiro1, Bruno Ramos Nascimento1 (1) Servico de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaude do Hospital das Clinicas da UFMG, Belo Horizonte - MG, Brazil; (2) Hospital Felicio Rocho, Belo Horizonte - MG, Brazil; (3) Hospital Mater Dei, Belo Horizonte - MG, Brazil Introduction: Catheter ablation is a well-established therapy for atrial fibrillation (AF), with a promising impact on heart failure (HF) outcomes. We aimed to evaluate the impact of AF ablation on echocardiographic and clinical parameters in patients with HF in Brazil, and to assess factors associated with improvement of the left ventricular ejection fraction (LVEF). Methods: Patients diagnosed with HF and LVEF <50%, who underwent radiofrequency AF ablation in 5 high-volume centers, were prospectively enrolled. All patients underwent standard transthoracic echocardiography before the procedure and during clinical follow-up, and the analysis by the examiner was considered. The primary outcome was LVEF normalization (LVEF >= 50%) at follow-up. Clinical, echocardiographic, and procedure-related variables associated with the primary outcome were assessed by univariate logistic regression. P-value <0.05 was considered significant. Results: From 2018 to 2022, 77 patients were included, being 52 (68%) males, mean age 66 +- 12 years. Of these, 27 were in NYHA functional class 3/4, 64 (83%) had persistent AF, and only 3 had previous ablations. Pre-procedural LVEF was 38 +- 7%, with 24 (31%) having LVEF < 35%. Complications occurred in only 3 patients (2 in vascular access and 1 endocarditis). In the 13 +- 11 month follow-up, there was a substantial improvement of the LVEF to 54 +- 14% (p < 0.001), and 54 (70%) achieved the primary outcome of LVEF normalization. Fifty-three patients (69%) had LVEF improvement of >=10%, only 7 remained in NYHA class 3/4, and AF recurred in 13 (17%). Three patients died during follow-up, and none had LVEF improvement. Predictors of LVEF normalization were: pre-ablation LVEF (OR = 1.23, 95%CI 1.11-1.36), baseline left atrial diameter (OR = 0.86, 95%CI 0.79-0.94), ischemic (OR = 0.29, 95%CI 0.08-0.98) and Chagasic (OR = 0.14, 95% CI 0.03-0.78) etiologies and prescription of amiodarone (OR = 0.26, 95%CI 0.09-0.78) and ACEi/ARB (OR = 0.24, 95%CI 0.07-0.81, p = 0.02). In the multivariable model, independent predictors were: baseline LVEF (OR = 1.20, 95% CI 1.06-1.27, p = 0.005), left atrial diameter (OR = 0.88, 95%CI 0.77-0.99, p = 0.03), ischemic (OR = 0.13, 95%CI 0.02-0.85, p = 0.03) and Chagasic (OR = 0.08, 95%CI 0.01-0.76, p = 0.03) etiologies. Conclusion: AF ablation in patients with HF resulted in remarkable echocardiographic and functional improvement, with low complication rates. Less clinical severity and less morpho-functional impairment were associated with LVEF normalization. 110563 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Effects of Mindfulness Meditation Associated with Transcranial Direct Current Stimulation on Heart Rate Variability in the Elderly EVELYN COSTA CRUVINEL1, Aline Teodoro Mendes1, Denise Mayumi Tanaka2, Fernanda Regina Moraes3, Gustavo Jose Luvizutto1, Marilita Falangola Accioly1, Luciana Duarte Novais Silva1, Douglas Reis Abdalla4, Eduardo Elias Vieira de Carvalho1 (1) Programa de Pos-graduacao em Fisioterapia da Universidade Federal do Triangulo Mineiro.; (2) Departamento de Clinica Medica da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo.; (3) Curso de Fisioterapia da Universidade de Uberaba.; (4) Departamento dos Cursos de Saude do Centro Universitario Talentos Humanos. Introduction: Aging is a physiological process that leads to decreased heart rate variability. Physical training is an established therapy that induces increased heart rate variability, and transcranial Direct Current Stimulation (tDCS) potentiates this beneficial effect. However, a large part of the elderly population does not have access to adequate physical training programs. Instead, meditation is an easily accessible and useful tool to induce small increases in heart rate variability. However, no studies have evaluated the effects of the association of meditation with tDCS on heart rate variability. Purpose: To evaluate the influence of meditation associated with tDCS on heart rate variability in the elderly. Methods: Eleven older adults of both sexes, aged 69.1 +- 7.2 years, were studied. Heart rate variability was collected in the supine position, in a quiet environment, free from the circulation of people and external influences, lasting 80 minutes, with 5 minutes of initial rest to control heart rate, followed by recording the RR intervals at 20 minutes baseline, 15 minutes meditation, 20 minutes tDCS and 20 minutes final/. The meditation technique was mindfulness, applied by a qualified and experienced therapist; tDCS was applied by an anodic current of 2 mA, following the international standards for the system (EEG10-20). Outcomes were analyzed using the ANOVA model with fixed effects. Results: It was observed a significant increase of the heart rate variability indexes with the techniques association: RMSSD from baseline (27.2 +- 35.9 ms) to post-meditation (33.6 +- 43 ms) and post-tDCS (36.7 +- 50.7 ms), p = 0.04; SDNN from baseline (23.8 +- 26.3 ms) to post-medidation (27 +- 28.3 ms) and post-tDCS (31.8 +- 34.5 ms), p = 0.0001; Low-frequency component from baseline (369.6 +- 602.4 ms2) to post-meditation (352.8 +- 599.1 ms2) and post-tDCS (672.2 +- 1034.1 ms2), p = 0.0001; High-frequency component from baseline (207.4 +- 375.5 ms2) to post-meditation (599.7 +- 1068.5 ms2) and post-tDCS (896.8 +- 1958.7 ms2), p = 0.0009; SD1 from baseline (19.2 +- 25.4 ms) to post-meditation (23.8 +- 30.4 ms) and post-tDCS (26 +- 35.9 ms), p = 0.02; e SD2 from baseline (27.4 +- 27.6 ms) to post-meditation (28.9 +- 27.2 ms) and post-tDCS (36 +- 34 ms), p = 0.0001. Conclusion: The results of the present study documented for the first time that the application of anodal tDCS can significantly enhance the beneficial effects of meditation on heart rate variability indexes in the elderly. 110632 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Left Ventricular Global Longitudinal Strain Three Months After COVID-19 Pneumonia YAROSLAVSKAYA E.I.1, Krinochkin D.V.1, Shirokov N.E.1, Gorbatenko E.A.1, Osokina N.A.1, Migacheva A.V.1 (1) Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences Background: COVID-19 can result in myocardial injury in the acute phase. The late cardiac consequences of complicated course of COVID-19 is limited. Purpose: To study the prevalence of disorders and the relationship of left ventricular global longitudinal strain (LV GLS) in patients with proven COVID-19 pneumonia 3 months after discharge from the hospital. Methods: 369 patients underwent a comprehensive clinical examination 3 months +- 3 weeks after discharge after COVID-19 pneumonia. The mean age was 52 +- 11 (from 19 to 84 years), 50.9% women. Standard echocardiography and myocardial strain assessment were performed. LV GLS was studied in 296 (80%) examined patients with optimal visualization quality. LV GLS was considered reduced when its value was above -18%. Results: 3 months after discharge, obesity was noted in 46.5% of patients, cardiovascular diseases were diagnosed in 73.4%. Arterial hypertension (AH) occurred in 71.5% of patients, coronary artery disease - in 22.5%. LV GLS was reduced in 25.1% of the patients. LV GLS showed no relationship with the patient age, NYHA functional class and LV ejection fraction (EF). Reduced LV GLS was independently associated with AH (OR 1.174; 95% CI 1.056-1.305; p = 0.003), obesity (OR 1.295; p < 0.0001), male sex (OR 0.734; 95% CI 0.657 -0.821; p < 0.001). LV GLS showed positive correlations of medium strength with echocardiographic parameters: length of the right (r = 0.308) and left ventricles (r = 0.306), LV mass (r = 0.326), anterior-posterior left atrial (LA) dimension (r = 0.303, all p < 0.0001). LV GLS showed a weak positive correlation with the severity of lung lesions during hospitalization (r = 0.134; p = 0.032), diastolic blood pressure (r = 0.230; p < 0.001), LV posterior wall thickness (r = 0.255, p < 0.001) and interventricular septum (r = 0.188, p = 0.001). Conclusions: Reduced LV GLS 3 months after COVID-19 pneumonia was observed in 25.1% of survivors and is associated with AH, obesity, and male sex. LV GLS was not associated with the patient age, NYHA functional class and LV EF. The correlation between impaired LV GLS and the severity of lung lesions in hospitalization was weak, the correlations with the ventricles length, LV mass, and LA anterior-posterior dimension were of medium strength. 110778 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS Functional Sarcopenia Phenotype Predicts Mortality in Older Adults with Cardiovascular Disease at 1 Year. Data from the Sarcos Study ALBERTO FRISOLI JUNIOR1, Elaine Azevedo1, Amanda kimura1, Angela Paes1, Valdir Ambrosio1 (1) Universidade Federal Sao Paulo The diversity of concepts of sarcopenia makes it difficult to use in clinical practice. Low performance on functional tests (functional sarcopenia) has been shown to be associated with severe outcomes, while low muscle mass (anatomic sarcopenia) has controversial results. Functional sarcopenia has phenotypes determined by the accumulation of physical dysfunctions, whose predictive value for mortality is not yet established. Objective: To evaluate if Functional Sarcopenia phenotypes are associated with mortality in elderly people with cardiovascular disease (CVD). Methods: SARCOS is a prospective cohort study on Sarcopenia and Osteoporosis with mortality in elderly with cardiovascular disease. Sample: Elderly outpatients of the Federal University of Sao Paulo - Brazil. Physical functions were evaluated by: walking speed (WS) in 4.5 mts, the time to sit and stand up from chair test (CST) and hand grip strength (HGS), by dynamometer. Appendicular muscle mass (AMM) was measured by DXA. AMM/height2, HGS, WS and CST were evaluated in quartiles. Functional sarcopenia (FS) phenotype was characterized according to the presence of weakness (HGS < 26 Kgf M, <16 Kgf W), low WS (LWS, if WS < 0.5 m/s) and high time to CST (HCST > 25s): Robust = 0, sarcopenia = 1, Functional Sarcopenia >=2. Mortality was assessed by telephone contact at 6 and 12 months. Significant mortality variables and low AMM according to EWGSOP II* and FNIH# were used in the regression. Results: Among the 555 subjects, 57.5% (n = 319) were women, mean age 77.91(7.27). Weakness occurred n = 151 (27.2%), LWS n = 156(28.1%) and HCST n = 129(23.2%). The prevalence of phenotypes: Robust n = 281 (50.6%), Pre FS n = 155 (27.9%), and FS n = 119 (21.4%). Mortality was 4.7% (n = 26), of which, n = 5 (19.2%) were robust, n = 7 (26.9%) Pre FS, and n = 14 (53.8%) had FS, (p < 0.001). The FS phenotype was characterized by being female, higher age, lower HGS and WS, higher Time to CST, higher functional loss (IADL and ADL), lower depression score, lower AMM/h2 and higher percentage of total body fat, compared to other phenotypes. In regression analyses for mortality, Pre FS OR: 1.84 (0.45-7.49, p = 0.390)* and OR: 2.30 (0.56-9.48, p = 0.247)#; and FS OR: 4.98(1.35-18.40; 0.016)* and OR: 7.06(1.71-29.09; p < 0.007)#. Conclusion: In the older adults with cardiovascular disease, Functional Sarcopenia phenotype predicts higher mortality compared to the other phenotypes, regardless of low muscle mass and CVDs. 110761 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Frailty and 5-Year Mortality in Patients with Congestive Heart Failure and Implanted Devices for Cardiac Resynchronization Therapy SOLDATOVA A.M.1, Kuznetsov V.A.1, Enina T.N.1, Bogdanova D.S.2, Benzineb F.T.2 (1) Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences; (2) Tyumen State Medical University Purpose: To access the prevalence of frailty and its impact on long-term prognosis in patients with implanted devices for cardiac resynchronization therapy (CRT). Methods: 77 patients with congestive heart failure (74% men, 26% women; mean age 58.7 +- 10.7 years) with NYHA class II-IV were enrolled. Frailty index (FI) was calculated using 31 parameters (the ability to perform daily activities, clinical status, laboratory markers, comorbidities). Based on the median of FI value patients were identified as not frail (<0.375; n = 41; 53%), and frail (>=0.375; n = 36; 47%). Results: The mean follow-up period was 38.0 [21.0; 66.0] months. The 5-year survival was 87.8% for not frail patients compared to 52.8% for frail patients (Log rank p < 0.001). In univariate analysis the presence of frailty was significantly associated with long-term mortality (HR 6.108; 95 CI 2.207-16.907; p < 0.001). After adjustment for age, gender, NYHA class, left ventricular ejection fraction, presence of left bundle branch block and QRS width frailty remained a significant factor associated with 5-year mortality (HR 5.763; CI 95% 1.837-18.083; p = 0.003). Conclusions: Frailty is widespread in patients with heart failure and implanted devices for CRT and it has an independent association with the risk of 5-year mortality. 110798 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Level of Knowledge and Safety Measures Adopted by Physiotherapy Professionals Working in Pilates Studios in Care Provided to Patients with Cardiovascular Diseases PRISCILLA MORETTO1, Priscilla Moretto1, Tatiane Boff Centenaro3, Gabriela dos Santos3, Fernando Rosa Inacio1, Ana Ines Gonzales1 (1) Centro Universitario Estacio de Sa de Santa Catarina; (2) Centro Universitario para o Desenvolvimento do Alto Vale do Itajai - UNIDAVI; (3) Universidade do Estado de Santa Catarina - UDESC Introduction: In physical exercise programs aimed at Cardiovascular Rehabilitation, it is important to emphasize the adequate monitoring of these patients for care in the event of a cardiovascular event. Given the above, questions arise whether these care and monitoring are performed by physical therapists who work with the Pilates Method in patients with Cardiovascular Diseases (CVD's) and if it occurs in an adequate and safe way. Objectives: To assess the level of knowledge and safety measures adopted by physiotherapy professionals working in pilates studios regarding the care provided to patients with cardiovascular diseases. Methodology: Cross-sectional research, with a non-probabilistic and quantitative sample, where professionals with active CREFITO, certified in Pilates and active in the method in the states of Brazil were invited. Those who did not provide all the data were excluded from the research. There was the development of a self-response questionnaire containing information related to the professional and the assessment of the level of knowledge regarding the approach and safety measures adopted with the Pilates Method in exercise programs for patients with CVD's. Professionals were invited to respond digitally and by publicizing CREFITOS and universities in Brazil. The TCLE was considered electronically signed when the volunteer accepted to participate in the research through an electronic form (Google Forms). The analysis of the study data was carried out using descriptive statistics, based on measures of central tendency (mean and standard deviation), performed in the SPSS statistical program for Windows(r) version 2.0. Results: 134 physical therapists answered the questionnaire, 98 (73.1%) do not have a training course in the cardiovascular area, 81 (60.4%) have practical knowledge in cardiopulmonary resuscitation, 68 (50.7%) are not up to date regarding rehabilitation guidelines and approximately more than 90% of professionals consider it important to check safety measures regarding vital signs before, during and after each session. In the event of any cardiovascular intercurrence, only 69 (51.5%) of the professionals stated that their team is prepared to assist. Conclusion: Most professionals do not have training to care for this type of patients, and have little knowledge of updating in the area, at the same time they consider it necessary to measure vital signs and perception of effort in the sessions. 110832 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Neutrophil/Lymphocyte Ratio is Correlated with Levels of Inflammatory Markers and is Significantly Reduced by Smoking Cessation MAKI KOMIYAMA1, Yuka Ozaki1, Yoichi Sunagawa2, Yasufumi Katanasaka2, Masafumi Funamoto2, Kana Shimizu2, Hajime Yamakage1, Noriko Sato-Asahara1, Hiromichi Wada1, Tatsuya Morimoto2, Koji Hasegawa1 (1) Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; (2) Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan Background: Inflammation of blood vessels is key in the process of coronavirus disease 2019 (COVID-19) aggravation. Besides, risk factors for COVID-19 such as cardiovascular disease is strongly associated with smoking habits. Previous studies have reported that neutrophil to the lymphocyte ratio (NLR), the inflammation marker, is associated with the onset and prognosis of cardiovascular (CV) disease. Smoking is a potent CV risk factor, and smoking cessation significantly reduces CV risk. However, the effects of smoking cessation on the NLR remain unknown. Purpose: The purpose of this study is to demonstrate the effect of smoking cessation on the NLR. Methods: Among smokers visiting our smoking cessation clinics, we examined changes in the NLR and CVD biomarkers before and after smoking cessation. A total of 389 individuals (301 men and 88 women) were enrolled in the study. Results: The median NLR was significantly reduced after successful smoking cessation (before: 1.8 [1.5, 2.5], after: 1.7 [1.3, 2.4]; p < 0.001). In a linear regression model adjusted for sex, percent change in NLR comparing before and after smoking cessation was significantly and positively correlated with percent changes in C-reactive protein (b = 0.260, p = 0.001), a1-antitrypsin-low density lipoprotein (b = 0.151, p < 0.05), and serum amyloid A-low density lipoprotein (b = 0.325, p < 0.001). Conclusion: Our study demonstrated for the first time that smoking cessation significantly reduces the NLR in tandem with markers of inflammation and oxidative stress. These results may suggest that smoking cessation improves the risk of developing cardiovascular diseases and more severe symptoms of COVID-19. Moreover, smoking cessation recovers airway ciliary clearance and immune function as early as one month. Thus, smoking cessation awareness is strongly encouraged as part of the public health measures aiming to limit the global impact of COVID-19. 110803 Modality: E-Poster Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Prevalence of Arterial Hypertension in a Sample of Adults in Luanda: A Comparative Analysis Based on the Most Recent American Guidelines HENRIQUE COTCHI SIMBO MUELA1, Guilherme Passassi1, Angelina Clara Cassoma Francisco1, Antonio Gerson Bastos Francisco1, Isaura da Conceicao Almeida Lopes1, Gade Satuala Vasco Miguel2 (1) Department of Physiology, Faculty of Medicine, Agostinho Neto University, Luanda, Angola; (2) Cardiothoracic Surgery Department, Girassol Clinic, Luanda, Angola Introduction: In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) published a new guideline (JNC 8) on the treatment of hypertension (HTN) that changed the diagnostic standard of high blood pressure (BP) from a BP threshold of 140/90 mmHg, as set by the seventh report of the Joint National Committee (JNC 7) to a BP of 130/80 mmHg. Objective: To carry out a comparative study on the frequency of HTN and the profile of BP levels in a sample of adult inhabitants in Luanda, Angola, based on the most recent American HTN guidelines. Methods: We carried out a cross-sectional study was, which included 1480 individuals who participated in the study on high blood pressure between May 2018 and June 2019, and who were recruited at Shopping Xyami, Angolan Public Television (TPA) and Congolenses' market. Sociodemographic, anthropometric and clinical data were collected. Each participant had his/her BP taken with three measurements on the arm, after a 5-minute rest, using a semi-automatic Omron(r) device (Kyoto, Japan), with a 1-minute interval between. HTN was defined as the mean of systolic blood pressure (SBP) >=140 mmHg and/or diastolic blood pressure (DBP) >=90 mmHg according to JNC 7 and the mean of SBP >=130 mmHg and/or DBP >=80 mmHg according to JNC 8 or use of antihypertensive drugs for both guidelines. Results: The sample was composed mostly by men (69.30%), young people (mean 39.74 +- 11.55 years old, range 18 to 94 years old). Alcohol consumption (74.6%) and overweight/obesity (44.9%) were the most prevalent risk factors. The prevalence of HTN was twice as high using the criteria proposed by the JNC 8 guideline compared to the cutoff points proposed by the JNC 7 (60.20 vs. 34.70; X2 = 519,03; p < 0.001). Both the knowledge and the treatment as well as the control of HTN were worse when using the JNC8 guideline definitions compared to JNC 7 guideline (X2 = 519,03; p < 0,001). Age, weight and alcohol consumption were the main predictors of blood pressure changes. Conclusion: The use of JNC 8 definition resulted in a significant increase in the prevalence of high blood pressure, placing the BP of a significant proportion of adults in the hypertension range. 110804 Modality: E-Poster Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Prevalence, Awareness, Treatment and Control of Arterial Hypertension in a Sample of Residents of Luanda, Angola HENRIQUE COTCHI SIMBO MUELA1, Angelina Clara Cassoma Francisco1, Guilherme Passassi1, Antonio Gerson Bastos Francisco1, Isaura da Conceicao Almeida Lopes1, Gade Satuala Vasco Miguel2 (1) Department of Physiology, Faculty of Medicine, Agostinho Neto University, Luanda, Angola; (2) Cardiothoracic Surgery Department, Girassol Clinic, Luanda, Angola Background: Arterial hypertension (HTN) is an important public health challenge worldwide. Data regarding the burden of hypertension is essential for the development of effective strategies for both treatment and control. Studies on the prevalence and awareness of hypertension in Sub-Saharan Africa (SSA) and especially in Angola are still scarce. Objective: To assess the prevalence, awareness, treatment and control of HTN in a sample of dwellers of Luanda. Methodology: We carried out cross-sectional study in a sample of dwellers of Luanda, Angola. Sociodemographic data and cardiovascular (CV) through questionnaires. Blood pressure was measured with semi-automatic sphygmomanometer (Omron(r), Model HEM-7131-E), after 5 minutes resting and seated. Three blood pressure (BP) measurements with a 1-minute interval between were used to determine SBP and DBP in each patient. The average of the two last blood pressure readings was used for the analysis. Hypertension was defined as SBP and/or DBP >= 140/90 mmHg or current use of antihypertensive drugs. Controlled hypertension was defined as blood pressure <140/90 mmHg under antihypertensive drugs. Results: Between May 2018 and June 2019, we carried out a cross-sectional study including 1480 individuals was carried out. The majority of the sample was young (mean age 39.74 +- 11.55 years old) and men (69.30%). Alcohol consumption (74.6%) and overweight/obesity was the most prevalent risk factors. The HTN prevalence was 34.9% in the sample. Among the hypertensive patients, 245 (47.4%) were aware of their disease and only 190 (36.8%) were under hypertension treatment; among those were taking drugs, only 68 (35.8%) were under control, defined as BP <140/90 mmHg. Conclusion: HTN prevalence was high; the awareness, treatment and control levels were low. 110806 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Neutrophil-Lymphocyte Ratio and Coronary Artery Disease Risk in Patients Undergoing Coronary Angiography HENRIQUE COTCHI SIMBO MUELA1, Fernando Muhongo Sandala1, Jose Antonio Tito2, Guilherme Mendes Lima Franco1, Antonio Gerson Bastos Francisco1, Isaura da Conceicao Almeida Lopes1 (1) Department of Physiology, Faculty of Medicine, Agostinho Neto University, Luanda, Angola; (2) Cardiology Department, Sagrada Esperanca Clinic, Luanda, Angola Background: Inflammatory response is one of the main mechanisms in the pathogenesis of atherosclerosis and its progression. The neutrophil-lymphocyte ratio (NLR) has been proposed as an inflammatory biomarker and potential risk and prognosis predictor in cardiovascular disease (CVD). Objective: To assess the association between the neutrophil-lymphocyte ratio and the severity of coronary artery disease. Methods: An observational and retrospective study was carried out, including 56 patients aged >=18 years (41 men and 15 women) who underwent diagnostic and/or therapeutic coronary angiography from 2014 to 2019 at Sagrada Esperanca Clinic, Luanda, Angola. Demographic data, risk factors and comorbidities, biochemical tests and full blood count were collected from the patients' medical reports. The NLR was calculated as the ratio between the total neutrophil and lymphocyte counts from the patients' full blood count. For the statistical analysis purposes, the sample was divided into two groups according to the median of NLR (median: 2.02): patients with NLR <= median and patients with NLR> median. The statistical significance was set at 5%. Results: The group of patients with CAD was relatively older than the group without CAD, although without any significant difference (58.49 +- 8.76 vs. 54.74 +- 8.7, p = 0.137). Likewise, the age was similar between groups considering the level of NLR (57.89 +- 8.60 vs. 56.54 +- 9.12, p = 0.571). The risk of having CAD and it being obstructive was twice as high in the group with NLR above the median (NLR > 2.02) compared to the group with a lower NLR (OR: 2.25, CI: 0.722-1.012 and 2.17, CI: 0.717-6.550, respectively). However, in general, our data suggested that there was no association between the neutrophil-lymphocyte ratio and the presence of CAD, nor with its severity (kh2 = 1.991, p = 0.259 and kh2 = 0.760, p = 0.562, respectively). Conclusion: The risk of CAD occurrence, as well as the occurrence of obstructive CAD was twice higher in the group with higher neutrophil-lymphocyte ratio. 110817 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING The Role of NT-Probnp and Echocardiographic Parameters in Patients with Acute Exacerbation of COPD SASHA KJAEVA ANASTASOVA1, Prof, d-r Srbinovska -Kostovska1, D-r. Paljoskovska-Jordanova1, D-r. Shehu1, D-r.Risteski1, D-r.Debreshlioska2, D-r. Angelovska2, D-r.Nivicka-Kjaeva3, D-r.Kjaev4 (1) University Clinic of Cardiology, Skopje, North Macedonia; (2) University Clinic of Pulmoallergology, Skopje, North Macedonia; (3) University Clinic of Ophthalmology, Skopje, North Macedonia; (4) University clinic of Gynecology, Skopje, North Macedonia Aim: The aim of the study was to evaluate which echocardiographic parameters in assessment of right ventricular function may contribute to risk stratification in patients with severe/very severe chronic obstructive pulmonary diseases (COPD) in correlation with biomarker Nt-proBNP. Material and methods: We have analyzed 38 patients with severe/very severe COPD, stages 3 and 4 according to Gold classification. All patients with heart diseases were excluded from the study. Additionally, all patients were divided into two subgroups: patients with acute exacerbation and chronically stable patients. Echocardiography, analysis included several parameters with emphasis to right chamber echo parameters in correlation to natriuretic peptide. Special emphasis was given to 3 predominant echocardiographic parameters: TAPSE, S' wave assessed by tissue doppler of the free wall of the right ventricle and FAC%. Results: Of a total number of 38 patients, 81,6% had elevated values of NT-proBNP and 18,4% had values of NT-proBNP in normal ranges. Analysis of the average values of NT-proBNP showed much higher values in the group of patients with acute exacerbation where the average value of NT-proBNP was 786,73 pg/ml in correlation with chronically stable patients, where NT-proBNP was 141,17 pg/ml. All 20 patients with acute exacerbation had elevated NT-proBNP values (above 125 pg/ml). In the group of patients with acute exacerbation, 13 patients (65%) out of 20 had S' wave from the tissue doppler below 0,095 m/sec and 8 patients (22,6%) had TAPSE below 16 mm. The group of chronically stable patients (who were 18 in number), showed not convincing results. In this group 61% (11 patients) of the patients had elevated NT-proBNP, 4 of them had S' wave from the tissue doppler below 0,095 m/sec and TAPSE was in normal range(>16 mm). FAC was below 35% in one patient, where NT-proBNP was 345,4 pg/ml. Conclusion: In patients with chronic obstructive pulmonary diseases (COPD), echocardiographic parameters TAPSE and S' wave assessed from the Tissue Doppler of the free wall of the right ventricle can be significant prognostic markers for disease monitoring. These parameters, especially S' wave, can also be a marker for acute deterioration of the condition of the patients with COPD. 110833 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Long-Term Follow-Up in Patients with Rheumatic Mitral Stenosis and Severe Pulmonary Artery Hypertension Submitted to Percutaneous Mitral Balloon Commissurotomy RAFAEL ALEXANDRE MENEGUZ MORENO1, J. Ribamar Costa Jr.1, Nisia Lira Gomes1, Auristela IO Ramos1, Alfredo N. Ferreira-Neto1, Dimytri Siqueira1, Mercedes Maldonado1, Zilda Meneghelo1, Cesar A. Esteves2, Sergio Braga1, Amanda Sousa1 (1) Instituto Dante Pazzanese de Cardiologia; (2) Universidade Federal de Sao Paulo (UNIFESP) Background: Percutaneous balloon mitral commissurotomy (PMBC) is an attractive therapeutic approach in patients with mitral stenosis. The aim of this study was to assess the immediate and long-term clinical, echocardiographic and haemodynamic outcomes of PMBC in patients with severe pulmonary hypertension (PH). Methods: Among all procedures (in more than two decades of experience), PMBC was performed from 1987 until 2011 at a single-center in 147 patients who had significant PH defined as baseline pulmonary artery mean pressure (PAMP) (systolic pulmonary pressure >75 mmHg). All-cause mortality, need for mitral valve replacement (MVR) or new PMBC, and valve restenosis were evaluated during follow-up yearly. Results: Mean age was 33.8 +- 12.8 years and 83.6% (123 patients) were women. Primary success was achieved in 89.8% of the patients (132 patients). Mitral valve area (MVA) increased from 0.83 +- 0.17 cm2 to 2.03 +- 0.35 cm2 (p < 0.001), and at 20-years, mitral valve area was 1.46 +- 0.34 cm2 (p = 0.235). Systolic pulmonary artery pressure decreased from 87.0 +- 6.0 mmHg to 60.0 +- 0.9 mmHg (p < 0.0001). The rates of all-cause mortality, need for MVR, new PMV, and valve restenosis were 0.67%, 20.0%, 8.78% and 30.4%, respectively, in long-term (mean 15.6 +- 4.9 years). Conclusions: PMBC is a safe and effective technique for the treatment of patients with mitral stenosis and PH. A significant decrease in pulmonary pressure was observed after commissurotomy. Although there was a gradual decrease of MVA at long-term follow-up, most patients remained asymptomatic and without major adverse events. 112450 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Trends in Cardiovascular Services and Procedure Volumes Across Different Phases of the COVID-19 Pandemic: An Analysis of 2019-2022 FATHIMA AAYSHA AAYSHA CADER1, Ishmum Zia Chowdhury2, Saidur Rahman Khan1, M. Maksumul Haq1, Mashhud Zia Chowdhury1 (1) Ibrahim Cardiac Hospital & Research Institute; (2) BIRDEM General Hospital Introduction: The impact of the COVID-19 pandemic on cardiology services globally has been variable, with a paucity of contemporary data comparing post-pandemic trends over a long period in a South Asian setting. Objectives: We aimed to report annual trends of cardiovascular services delivery and procedure volumes from 2019 to 2022, to assess the impact of the COVID-19 pandemic, and recovery of services at a tertiary cardiac centre in Bangladesh. Methods: Data on patient visits (outpatient and emergency), admissions, procedures and catheterization volumes were collected from January 2019 to February 2022 via hospital electronic records. Differences for each month of the preceding year were expressed as a percentage (%D). Trends (2019 to 2022) were graphically depicted via line diagrams. Results: Following significant reductions of all cardiology services in 2020 (1), particularly ER visits (D-59.5%; p = 0.0), cardiology services delivery and procedure volumes had recovered, reaching almost pre-pandemic levels by Q1 of 2021 . A steep and significant decline of admissions and procedures was seen in March-April 2021 as compared with 2020, coinciding with the Delta variant surge (2). By Q4 of 2021, patient visits and procedures, both outpatient and catheterization volumes had once again reached near pre-pandemic levels (3). During the Omicron surge in early 2022, a small decline in outpatient visits (D-10.9%) and outpatient procedures (D-6.83%) was observed in January-February. However, in-patient admissions (D4.39%) and catheterization laboratory procedures (D5.7%) showed a rise in February 2022 as compared with the preceding month, with ER visits showing the steepest rise (D 41.9%). Notably, although ER visits remained relatively blunted post-pandemic (2020-2021), this trend was not reflected in outpatient visits/procedures, in-patient admissions and catheterization procedures, all of which increased to pre-pandemic levels by the end of 2021 (1-3). This may be explained either by patients presenting at index to the outpatient department, instead of the ER; or, a higher proportion of patients being directly referred to our centre for admission from the peripheries. Conclusion: Two years on from the pandemic, cardiology services and cath lab volumes have reached almost pre-pandemic levels in 2022, except for ER visits which remain low, albeit gradually rising. 110840 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Pretreatment with P2Y12 Inhibitors in ST-Elevation Acute Coronary Syndrome (STEACS). Should We Keep Doing?: Systematic Review and Meta-Analysis LUIZ FERNANDO KUBRUSLY1, Douglas Mesadri Gewehr2, Taiane Belinati Loureiro Kubrusly3, Fernando Bermudez Kubrusly3, Luiz Fernando Kubrulsy1 (1) Mackenzie Evangelical School of Parana, Curitiba, Parana, Brazil; (2) Denton Cooley Institute of Research, Science and Technology, Curitiba, Parana, Brazil; (3) Curitiba Heart Institute, Curitiba, Parana, Brazil Background: The practice of pretreatment with oral P2Y12 inhibitors in ST-elevation acute coronary syndrome (STEACS) remains common; however, its association with improved cardiovascular outcomes is unclear, since no large RCT has addressed this issue. Objective: We aimed to evaluate the association of oral P2Y12 inhibitor pretreatment in STEACS patients with cardiovascular and bleeding outcomes. Methods: PubMed, MEDLINE, Embase, Cochrane, Scopus, Web of Science were systematically searched for studies that compared pretreatment with P2Y12 versus no pretreatment in STEACS, and reported efficacy and safety outcomes. A meta-analysis using a fixed and random effects model was used to calculated outcomes of interest. Heterogenicity was assessed with I2 statistics. Results: A total of 3 RCTs and 14 observational studies assigning 91,771 patients to either pretreatment (65,598 patients) or no pretreatment (26,171 patients) were included. Follow-up ranged 7 days to 19 months. Medications included clopidogrel, prasugrel and ticagrelor. At 30 days, P2Y12 pretreatment was associate with lower 30-day mortality (risk ratio [RR], 0.71; 95% CI, 0.56-0.91; p = 0.006; I2 = 75%), stent thrombosis (RR, 0.33; 95% CI, 0.12-0.95; p = 0.04; I2 = 83%), 30-day major bleeding (RR, 0.81; 95% CI, 0.74-0.90; p < 0.0001; I2 = 0%). No difference in the incidence of 30-day myocardial infarction (MI), target vessel revascularization (TVR), MACE (death/MI/TVR), stroke, pre-PCI TIMI 0 and post-PCI TIMI 0-2 was observed. Subgroup analysis for 30-day mortality, including only randomized studies, indicated a trend in favor of no pretreatment, but without statistical significance (RR, 1.49; 95% CI, 0.89-2.52; p = 0.13; I2 = 38%). Conclusion: In this study, pretreatment with oral P2Y12 inhibitors among patients with STEACS before cath lab, compared with treatment once coronary anatomy is known, was associated with decreased all-cause mortality and bleeding risk. 110852 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Nanumsmart: An Innovative Nanofunctionalized Polymerless Endovascular Platform CHRISTIANE DIAS MAUES1 (1) Smart Vascular Technologies EI; (2) Federal Government of Brazil ME/MCTI In recent years, nanotechnology has been a strong ally to medical technology advances, and in this sense, one of the greatest applications concerns drug carrying and releasing systems. The use of nanostructured systems to carry out drug delivery allows the development of new systems for an efficient transport of these drugs, where a controlled release is achieved to the diseased tissues of living systems. These drugs are linked to nanostructures in a controlled way, commonly called functionalization, along with other attached molecules - biomarkers. Smart nanoparticles as liposomes could still be functionalized for a better targeting to the target tissue, preventing the side effects of the drug they carry. As a pioneer project, this privilege holds a non polymeric multidrug eluting coronary stent, which spatial structure is represented by six configurations, associated to a biological matrix (coating) in which nanoparticles, more precisely functionalized liposomes, are stored and grouped into sequential layers, each one differing the type of pharmacological agent to be applied, as well as increased coefficients of biodegrability applied to this support matrix, conferring continuously and selectively control of drug releasing pulse. In this sense, nanofunctionalized liposomes, in addition to being cell membranes models, act as excellent biocompatible systems for formulation, carrying and release of drugs to organic tissues. 110846 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION RR Interval Analysis Program as a Predictor of Interventions in Implantable Cardioverter-Defibrillator Patients MICHAL LEWANDOWSKI1, Ilona Kowalik1 (1) National Institute of Cardiology, Warsaw, Poland Background: Prediction of sudden cardiac death remains a significant challenge. There is some evidence that ventricular ectopic activity could be regarded as a predictive marker. Objectives: We carried out an analysis to explore whether premature ventricular complexes (PVCs) are a risk factor in implantable cardioverter-defibrillator (ICD) interventions. Materials and methods: The study method was a RR interval series analysis (n = 184) of arrhythmic events and controls from the ICD. Study group consisted of patients with a mean age of 55 +- 27 years; 74% of them were male, 85% were secondary prevention patients, 62% had coronary artery disease (CAD), 15% hypertropic cardiomyopathy (HCM), 15% dilated cardiomyopathy (DCM), and 8% diseases of other etiol!ogy. The mean follow-up time was 64 months (range: 3-126 months). The study population was divide into patients with at least 1 appropriate intervention ventricular tachycardia/ventricular fibrillation (VT/VF) (group A, n = 101) and controls without interventions (group B, n = 83). The number of PVC/4000 RR cycles, the shortest coupling intervals between a PVC and preceding R as well as the number of PVCs of very short (180-220 ms), short (220-280 ms) and different cycle lengths (CL) as well as the incidence of short-long-short (SLS) sequences were compared. Results: The number of PVCs/4000 RR cycles was significantly higher in group A (263 +- 32 compared to 43 +- 17, p < 0.0001). The mean shortest PVC CL was significantly shorter in group A (320 +- 13 compared to 400 +- 38, p = 0.029). The number of PVCs with a very short CL was 1 +- 0.4 compared to 0.1 +- 0.1 (p = 0.028). The number of PVCs with a short CL was 5 +- 1.2 compared to 0.6 +- 0.4 (p = 0.0007) in groups A and B, respectively. The incidence of SLS sequences was significantly higher in group A than in group B (67 (94% of patients) and 4 (33% of patients) respectively (p < 0.0001)). Conclusions: Significant differences were found in the characteristics of PVCs and SLS sequences between patients with appropriate ICD interventions and controls. A newly developed basic computer program called PCRR was applied for RR interval analysis. This simple method could be a predictor of PVC burden, heart rhythm variability and life-threatening arrhythmias in different populations. 110878 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Genotyping of Patients with Hypertrophic Phenotype in a Latin American Cardiovascular Reference Center MARIA JULIANA RODRIGUEZ GONZALEZ1, Andres Felipe Barragan Amado1, Maria Fernanda Tamayo Tamayo1, John Alexander Ramirez1, Julian Gelves1, Esther Campos1, claudia Patricia Jaimes Castellano1 (1) Lacardio Introduction: In the setting of hypertrophic phenotype, the hypertrophic cardiomyopathy (HCM) is the most prevalent genetic disorder and responds to the 60% of the cases; with variable penetrance and expression. Genotyping is a step in its approach to defining prognosis and establishing phenocopies. Mutations in some genes encoding sarcomere proteins like cardiac myosin-binding protein C and b-myosin heavy chain are the most prevalent affected, representing 30-40% of all pathogenic or likely pathogenic variants. Aim: Describe the genotyping of our first cohort of hypertrophic phenotypes in a reference heart failure clinic. Method: Data was taken for in-Hospital patients irrespective of the cause of hospitalization or out of hospital who required a cardiovascular imagen test; the only requirement was to have a cardiac magnetic resonance or transthoracic echocardiography with a hypertrophic phenotype defined by any wall over 15 mm or 13 in patients with a family history of HCM between 01/01/2019-31/12/2021. Descriptive statistics are presented as median (range) or % of affected patients. Results: Patients with hypertrophic phenotype were 45, the average age was 54 years (ds: 19,73), 52% were women, 37% had a previous diagnosis of hypertension, the MYH7 was detected in 36% of the overall patients, and the total gene mutations were 55 and the unknown significance variants represented the 69%. Nine of these patients had multiple mutations and only three patients had non-sarcomere genes mutation (they had late-onset Fabry disease, amyloidosis, and Noonan). On the imaging aspects, the average diameter was 17,86 mm (ds: 4,16), the most affected segment was anteroseptal basal with 45% and the average left ventricular ejected fraction was 59,3 (ds: 15,01). Conclusion: These results provide important knowledge about genotyping patients with hypertrophic phenotype, to determine the possible diagnosis, the gene mutation, the type of variant, and the significance. This study shows that in our population, the pathogenic variants represent 27% of the total, similar data in comparison with the available publications. This is the first study in Colombia that reveals genotyping in hypertrophic phenotype could let us establish some mutations that carry a worse prognosis and establish family approaches. 111055 Modality: E-Poster Researcher - Non-case Report Category: PSYCHOLOGY Gender Differences in Nicotine Dependency and Depressive Tendency Among Smokers MAKI KOMIYAMA1, Hajime Yamakage1, Noriko Satoh-Asahara1, Yuka Ozaki1, Tatsuya Morimoto2, Yuko Takahashi1, Koji Hasegawa1 (1) Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; (2) Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan Depressive tendency and nicotine dependency are factors related to the failure of smoking cessation. Women generally have a higher depressive tendency and difficulty in smoking cessation than men. However, the impact of sex differences on the relationship between nicotine dependency and depressive tendency remains unclear. We evaluated 727 patients (496 men and 231 women) who visited our outpatient clinic for smoking cessation therapy and compared various parameters measured between sexes during consultation. Age, duration of smoking, and daily cigarette consumption were significantly higher in men during the first visit. Women had significantly higher self-rating depression scale (SDS) scores and took significantly more antidepressant drugs than men. The SDS score significantly correlated with the Fagerstrom test for the nicotine dependence score and with daily cigarette consumption in women, but not in men. Thus, the present study demonstrates the differential relationship of depressive tendency with tobacco use or nicotine dependency in men and women, which might reflect sex differences in response to psychological stress. We previously reported that depressive tendencies of patients with neurosis improve even in the initial stages of the smoking cessation treatment (i.e., within two weeks after starting the treatment), but further studies are required for the sex difference for the improvement. 110894 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES A Multicenter Case Series of Late Prosthetic Valve Endocarditis and Analysis of Risk Factors for Mortality CRISTIANE DA CRUZ LAMAS1, Giovanna Ianini Ferraiuoli Barbosa1, Rafael Quaresma Garrido1, Wilma Felix Golebiovski1, Clara Weksler1, Diego Santos2, Caio Sambo2, Vitor Milczwski2, Milena Paixao3, Flavio Tarasoutchi3, Tania Mara Varejao Strabelli3, Rinaldo Focaccia Siciliano3 (1) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (2) Department of Infectious Diseases, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil; (3) Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil Introduction: Prosthetic valve endocarditis (PVE) is found in 10 to 30% of contemporary series of infective endocarditis (IE) and has a high mortality rate. Our aim was to describe cases of late PVE and analyze mortality-related risk factors. Methods: Two quaternary cardiac surgery institutes were the study scenarios. Data were collected from 2011-2021 in site 1, and 2006-2021 in site 2. Patients were prospectively identified using site-specific procedures to ensure consecutive enrollment. Only adult patients with definite IE according to the modified Duke criteria were included. Studied variables were those present in the International Collaboration in Endocarditis case report forms. Statistical analysis was performed with the SPSS v26 software. Variables with p values less than 0.1 were included in the model. Results: There were 250/559 (44.7%) episodes of LPVE in site 1 and 77/438(17.6%) in site 2 during the study periods. Males accounted for 207/327 (63.3%) of patients, mean age +- SD was 55.5 +- 17.3 years. Rheumatic valve disease was present in 161/326 (49.4%) and congenital heart disease in 29/327(8.9%). Healthcare-associated IE was present in 83 (25.4%) and 132/326(49.4%) patients were in heart failure (NYHA class III/IV). Etiologic agents were defined in 275(84.1%) of cases, and oral streptococci were responsible for 107/327(32.7%). Death was the outcome for 101/327(30.9%). Risk factors for death were assessed by multivariate analysis and those found to be statistically associated were: age over 60 years (OR = 2.4; 95% confidence interval [95%CI]: 1.2-5; p = 0.014), heart failure (NYHA class III or IV) (OR = 4.1; 95%CI = 1.8-8.3; p < 0.0001), the presence of perivalvular abscess/fistula/perforation on admission echocardiography (OR = 2.8; 95%CI = 1.3-6.1; p = 0.009) and being referred from another hospital (OR = 2.6; 95%CI = 1.25-5.4;p = 0.011). Conclusion: Previous series have described that late PVE is found in older patients, but our cohort shows younger patients and a high frequency of rheumatic valve disease. A quarter of patients acquired IE in a healthcare setting, highlighting the relevance of this mode of acquisition and the extra care needed in infection control in patients with prosthetic valves. Similarly to other studies, destructive disease and heart failure were associated with death, and mortality was higher than in native valve IE. 110902 Modality: E-Poster Researcher - Non-case Report Category: DYSLIPIDEMIA Plasma Lipoprotein(A) Concentration Among Acute Myocardial Infarction Patients KU MING YING1, Shirley Tan Siang Ning1, Crystal Tan Sing Yee1, Tiong Lee Len1, Saiful Shakirin bin Rosli1, Hwang Siaw San2, Ong Tiong Kiam3, Alan Fong Yean Yip3 (1) Sarawak General Hospital; (2) Swinburne University of Technology Sarawak Campus; (3) Sarawak Heart Centre Introduction: Lipoprotein(a) [Lp(a)] is known to have prothrombotic, proinflammatory and proatherogenic properties contributing to Atherosclerotic Cardiovascular Disease (ASCVD) development and progression. Previous studies have shown ethnic differences in plasma Lp(a) levels. Objective: We aim to determine the plasma Lp(a) concentrations among Malaysians with Acute Myocardial Infarction (AMI). Methods: This prospective study involved AMI patients admitted to a tertiary hospital in Sarawak between August 2018 and March 2019. Blood samples were collected during hospital admission and stored at -80degC. Plasma Lp(a) concentrations were determined by quantitative sandwich enzyme immunoassay technique (Elabscience, USA). Results: A total of 240 AMI patients were recruited, with mean age of 56.4(+-10.90) years and 88.8% males. Ethnic distributions were 42.9% Malay, 30.4% Chinese and 26.7% Iban/Bidayuh. The mean Lp(a) concentration and baseline LDL-C level were 5.3(+-7.49) mg/dL and 3.2(+-1.15) mmol/L respectively. Mean Lp(a) concentrations among Malay, Chinese and Iban/Bidayuh patients were similar [5.9(+-6.69) vs 5.3(+-10.46) vs 4.5(+-3.80) mg/dL; p = 0.340]. Patients with or without prior statin therapy demonstrated no significant difference in Lp(a) concentration [5.7(+-9.71) vs 5.1(+-5.53) mg/dL; p = 0.521]. Only 1.7% of patients were found to have Lp(a) >30 mg/dL. Patients presenting with 1-year MACE (AMI, stroke or cardiovascular death) were found to have significantly higher Lp(a) compared to those who did not [7.9(+-7.67) vs 4.96(+-7.41) mg/dL; p = 0.042]. Conclusions: Our study showed that the mean Lp(a) concentration among our AMI patients were lower compared to other published studies. However, those who experienced 1-year MACE had significantly higher Lp(a) concentration compared to the rest of the study population. 110904 Modality: E-Poster Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE The Role of NT-Probnp in Patients with Acute Exacerbation of COPD SASHA KJAEVA ANASTASOVA1, Prof, d-r. Srbinovska-Kostovska1, d-r Pajloskovska-Jordanova1, d-r Shehu1, d-r Risteski1, d-r.Debreshlioska2, d-r Angelevska2, d-r.Nivicka-Kjaeva3 (1) University clinic of cardiology, Skopje, North Macedonia; (2) University clinic of pulmo-allerology, Skopje, North Macedonia; (3) University clinic of ophthalmology, Skopje, North Macedonia Aim: The aim of the study was to evaluate chronic obstructive pulmonary diseases (COPD) in correlation with natriuretic peptide biomarker Nt-proBNP with special emphasys to the subgroup of acute exacerbation patients with COPD. All patients analysed were hospitalized. Material and methods: We have analysed 94 patients with COPD devided in 4 groups according to Gold classification system. Gold class I (18 pat.), Group II (18 pat.), Gold class III and IV (28/30 patients). Additionally, all patients were divided into two subgroups: patients with acute exacerbation and chronically stable patients. From the whole group of 94 patients, 63 were patients with acute exacerbation while 31 was were classified as chronically stable patients. Results: Natriuretic peptide was measured in all 94 patients with the average value above reverence ranges in all pts and it was 236.27 pg/ml. Gold class I/II included patients only with acute exacerbation. In both groups (Gold I/II), values od Nt-proBNP were at a higher level (159, 62 pg/ml). The average value of Nt-proBNP in Gold class III, in the group of acute exacerbation was 492,60 pg/ml versus 147,48 pg/ml in the group of chronic stable patients while in Gold class IV these values were 307,44 versus 151,74 pg/ml. The average values in acute patients are far higher then in the chronic group of stable COPD patients with in appropriate Gold class. Such a difference is almost 3,5 times higher in Gold class 3 and 2 times in Gold class 4. Conclusion: According to the results here is a clear and statistically highly significant difference in the values of Nt-proBNP in relation to acute and chronic COPD patients, especially in Gold class III and IV. In the acute group, this is all due to rich inflammatory process and deterioration of the lung function which is replicated on the right heart cavities resulting in high release of Nt-proBNP. Deterioration of lung function leads to right heart strain and weakness and increased excretion of Nt-proBNP. 110924 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES A Contemporary Prospective Cohort of Adult Patients with Infective Endocarditis in Brazil: Distinct Features CRISTIANE DA CRUZ LAMAS1, Nicolas de Albuquerque Pereira Feijoo2, Thatyane Veloso de Paula Amaral de Almeida2, Mariana Giorgi Barroso de Carvalho2, Gabriel Santiago Moreira1, Leo Rodrigo Abrahao dos Santos2, Rafael Quaresma Garrido1, Bruno Zappa1, Giovanna Ianini Ferraiuoli Barbosa1, Wilma Felix Golebiovski1, Marcelo Goulart Correia1, Clara Weksler1 (1) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (2) Unigranrio-Afya Introduction: Infective endocarditis is a severe disease, with high mortality. Its features in a developing country such as Brazil differ substantially. Our aim is to describe a series of adult patients with IE cared for in a cardiac surgery referral center, highlighting its specificities. Methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Patients were identified prospectively using site-specific procedures to ensure consecutive enrollment. Statistical analysis was performed using the Jamovi 1.6 and R 4.0.1 softwares. Results: There were 435 episodes of IE in the study period, and mean age +- SD was 47.8 +- 17.3 years; 283(65.1%) were males. Community-acquired IE occurred in 284 (65.4%), hospital-acquired in 112 (25.8%). Early prosthetic valve IE (PVE) accounted for 47/435(10,8%) cases and late PVE for 77(17,7%). Previous 170 (39.3%) had previous cardiac surgery, congestive heart failure in 173 (40.0%), chronic renal failure in 91 (21.0%), coronary artery disease in 60 (14.0%), diabetes mellitus in 55 (12.6%). Main predispositions to IE were rheumatic valve disease (RVD) in 133 (31.5%), valvular prosthesis in 28.5%, congenital heart disease in 61 (14.0%), previous IE in 51 (11.8%) and intravenous drug use in 5 (1.2%). Vegetations were seen in the mitral valve in 214 (49.4%) and aortic valve in 180 (41.6%), in intracardiac devices, in 33 (7.6%). Fever was seen in 91.7%, new regurgitant murmurs in 54.4%, embolism in 48.3%, splenomegaly in 20.4%; Osler's nodes, Janeway lesions, subconjunctival hemorrages and splinters were seen in less than 5% each. CRP levels were high in 82.3% and ESR in 58.9%. Blood cultures were taken in 98.6% of episodes, but were positive in only 67.1%. The most frequently isolated pathogens were viridans group streptococci, VGS(21%), S.aureus (11%), and enterococci(11%). Main complications were acute heart failure, in 263 (60.7%), acute renal failure (33.9%), myocardial abscess (22.6%). Surgery was indicated for 373 (86.1%) and effectively done for 316 (79.8%). Inhospital mortality was 109/425 (25.6%). Conclusions: In our quaternary center in Rio, left-sided IE predominated, with negative blood cultures or VGS as main findings. RVD was the main predisposition. Surgical indication was frequent, due to referral bias, and mortality was overall similar to the literature. 110942 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Impact of Early Exercise-Based Cardiac Rehabilitation on Hostility, its Behavioral Components, and Disease Perception in Patients After Myocardial Infarction IWONA KORZENIOWSKA-KUBACKA1, Anna Mierzyn'ska PhD2, Ewa Rydzewska PhD1, Edyta Smolis-Bak PhD1, Rafal Dabrowski MD, PhD1 (1) National Institute of Cardiology, Warsaw, Poland Department of Coronary Artery Disease and Cardiac Rehabilitation; (2) Department of Rehabilitation. Medical Centre of Postgraduate Education Gruca Orthopaedic and Trauma Teaching Hospital, Otwock, Poland Introduction: Hostility and its behavioral components, anger and aggression are psychosocial risk factors for coronary heart disease. The impact of exercise training on these negative emotions in patients after myocardial infarction (MI) without psychological support, has been poorly studied. Objective: The purpose of the study was to evaluate the effectiveness of physical training on the level of negative emotions, the cognitive aspect of adaptation to disease, and physical capacity in patients after MI who participated in cardiac rehabilitation. Methods: We enrolled 60 post-MI men and women in the study. All of them underwent an 8-week training program(TP) consisting of 24 interval trainings 3 times a week, started on average 40 days after MI. Before and after completion of TP, patients underwent a symptom-limited exercise test with analysis of maximal workload, duration, HR and BP at rest and during effort. The Buss-Perry Aggression Questionnaire assessing the level of negative emotions and the Brief Illness Perception Questionnaire were performed with results analysis in the entire group and subgroups of men, women, patients under 60 years of age (younger) and over 60 years of age (older). Results: After TP a significant reduction in the general level of negative emotions was found only in the group of younger: 67.8 +- 4.6 vs 63.9 +- 3.7 points, P < 0.01. Furthermore, a significant reduction in the sense of the impact of the disease on life was found in younger 6.96 +- 0.5 vs 5.48 +- 0.5points, P < 0.01. Furthermore, there was a significant improvement in overall adaptation to the disease in the subgroup of women from 40.6 +- 2.2 to 35.7 +- 1.9 points, P < 0.05. Physical capacity increased significantly in all studied groups. Conclusions: Participation in rehabilitation based on exercise trainings without psychological intervention not only improved physical capacity, but also beneficially contributed to a decrease in negative emotions and had a positive effect on disease adaptation especially in younger patients under 60 years of age after MI. 110949 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Evaluation of Echocardiographic Parameters for Right Heart Function and Pulmonary Hypertension in the Progression of Chronic Obstructive Pulmonary Disease SASHA KJAEVA ANASTASOVA1, Prof.D-r.Elizabeta Srbinovska-Kostovska1, D-r Elena Grueva-Nastevska1, D-r Savetka Paljovskovska-Jordanova1, D-r Dean Risteski1, D-r Danica Petkoska-Spirova1, D-r Enes Shehu1, D-r Irina Angelovska2, D-r Angela Debreshliovska2 (1) University clinic of cardiology, Skopje, North Macedonia; (2) University clinic of pulmo-allerology, Skopje, North Macedonia Aim: The aim of the study was to evaluate the echocardiographic parameters used to assess right ventricular function and pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD) according to their specificity and sensitivity and disease progression. Material and methods: We have analysed 94 patients with COPD (Gold class I-IV). The 13 echo-cardiography parameters important for assessment of right ventricular function and pulmonary hypertension due to their sensitivity and specificity and progression of the disease were evaluated: basal dimension of the right ventricle(DV bazal), right atrium(DA), right atrial area(DA area), S'wave of the right ventricle of TDI, TAPSE, functional area change (FAC%), (SPAP), Vmax of tricuspid regurgitation, acceleration time of pulmonary artery (AT), pulmonary vascular resistance (PVR), myocardial performance index of the right venricle (MPI), global strain of the right ventricle(GL strain), collapsibility of vena.cava inferior >/<50%. Results: Predictors of disease progression with high specifity and sensitivity are the parameters: MPI DV TDI, Global strain of DV and collapsibility of v.cava inferior less then 50%. Predictors of disease progression with high specifity and low sensitivity are: DV bazal, DA, DA area, S TDI, TAPSE, FAC, SPAP, V max TR. Predictors of disease progression with low specifity and high sensitivity are parameters: shortened acceleration time of the pulse Dopler of the pulmonary valve and the development of pulmonary vascular resistance. Conclusion: Echocardiography is a non invasive and useful method for evaluation and follow up the patients with COPD. All this indicates that the values of certain echo parameters can help us detect disease progression with high sensitivity, specifity or both. 110955 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Extended Electrocardiographic Screening for the Subcutaneous Implantable Cardioverter-Defibrillator (SICD) MICHAL LEWANDOWSKI1, Rafal Waligora1, Pawel Syska1, Ilona kowalik1 (1) National Institute of Cardiology, Warsaw, Poland Background: The condition for SICD therapy is passing an electrocardiographic screening test (ECG-s). A patient is considered suitable for implant if at least one surface ECG lead (sense vector) is acceptable for all tested postures. Objective: Identifying the rate of failure, the predicting factors and clinical importance of extended ECG-s with right sided lead position and lying on the left and right side of the body. Methods: ECG-s is based on a manufacturer-specific measurement tool. We performed this test in 50 consecutive pts with indication for SICD using standard protocol(lead at the left sternum border: sitting, standing and lying) and extended for right parasternal lead location and 2 additional position: lying on the left and right side. We analyzed age, gender, BMI, heart rate, rhythm(sinus/atrial fibrillation), QRS duration, PR interval, corrected QT interval(QTc), echocardiography parameters, etiology. Results: ECG-s failure occurred in 4/50(8%) of patients. Screening results: 1 vector failure rate with the standard device and electrode positions: primary(P) 12%,seconadary(S) 17%, alternative(A) 40%, P vs. A and S vs. A p < 0,001. Testing with an electrode positioned on the right sternum vector failure: (P) 10%,seconadary(S) 17%, alternative(A) 48%, P vs. A and S vs. A p < 0,001. In case of failure on left side 50,14 and 6% of pts passed the test with the right sided lead position for P, S and A vector respectively, p < 0.001. Identified factors predicting ESG-s passing vs. failure included: QTc interval 445,32 +- 35,4 vs. 480,6 +- 37,6 ms for any vector(p = 0,034), BMI:26,7 +- 4,7 vs. 29,9 +- 4,7 for vector A(p = 0,008), EF: 43,3 +- 20,1 vs. 34,0 +- 16,2 for vector A(p = 0,027). Sense vector failure rate with the left parasternal lead location lying on the left and right side of the body was concordant with lying on the back, p = 0,65. For the right parasternal lead location the rate failure was lower lying on the right side for all sense vectors: P, S and A(p = 0,045; 0,083 and 0,020) respectively. Conclusions: ECG screening failure rate for SICD is comparable with previous reports. The right parasternal lead location screening enables important clinical findings before implantation and in case of lead reposition during procedure, thus we recommend to screen routinely on both sternum borders. Some additional body position testing: lying on the left and right side of the body, mimicking sleeping/rest could be an important element to determine eligibility for SICD. 110961 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Interventions, Complications and Survival Among Transvenous and Subcutaneous Implantable Cardioverter-Defibrillator Patients Under Thirty Years of Age MICHAL LEWANDOWSKI1, Pawel Syska1 (1) National Institute of Cardiology, Warsaw, Poland Background: Young implantable cardioverter-defibrillator (ICD) recipients present high rate of inappropriate shocks(IS) and complications. Some of them seem to be underestimated. The subcutaneous ICD system was developed to eliminate lead-related complications and was proved to be effective. S-ICD appears to be a good therapy option and an alternative to transvenous implantable cardioverter-defibrillator (TV-ICD) in pediatric and young patients population. Aims To report on our clinical experience with TV-ICD and S-ICD therapy in patients under thirty years of age. Methods: We reviewed database of ICD recipients in our institution between 1996 and 2021(25 years) and have chosen 115 pts consecutively implanted up to and including the age of 30 years. We retrospectively analyzed the rate of appropriate and inappropriate interventions, lead complications rate, infection rate, mortality and treatment options. Results: The study group: 84 TV-ICD(age: 6-30, BMI: 16,3-22,2) and 31 S-ICD (age: 15-30, BMI; 15,6-31,1) patients. The mean follow-up in analyzed groups was 159 +- 48 and 36 +- 2 months respectively. Abnormal ventricular function: EF < 30 occurred in compared groups: 12/84(14%) and 5/31(16%) respectively, p = 0,3. 24/84pts(28%) received >=1 appropriate therapy(AT) for VT/VF(ATP or shock) in TV-ICD and 3/31pts(10%) in S-ICD groups. 25/84 pts(30%) had one or multiple (IS) and 0% in compared groups respectively, p = 0,02. There were 18/84 (21.5%) ventricular lead dysfunctions(reimplantation of a new system) in TV-ICD and 0% in S-ICD groups, p = 0,025. An infection rate (endocarditis or device pocket) was 6/84 (7%) in TV-ICD group with complete system removal and 1 pts (3%) wound infection in S-ICD group successfully treated with antibiotics. Mortality rate was 6/84 pts (7%), caused by ventricular lead dysfunction, end stage heart failure or heat transplantation fatal result in TV-ICD group. There was no death in S-ICD group. Conclusions: Endocardial ICD implantation in children and young adults is a feasible and effective procedure in a 25-year follow-up but the rate of complications is high in this population. S-ICD recipients did not experienced lead failures, systematic infections or inappropriate shocks. S-ICD appears to be a good therapy option in life-threatening arrhythmias, preventing from some serious T-ICD complications in young patients. The method and follow-up period effect is present between the TV-ICD and S-ICD in analyzed groups. 110968 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Less Physical Activity and Increased Screen Time are Associated with Higher Stress Levels at School in Lithuania Adolescents PRANAS SERPYTIS1, Egle Majauskiene1, Pranas Serpytis1 (1) Vilnius University, Faculty of Medicine, Lithuania; (2) Vilnius University, Clinic of Cardiac and Vascular Diseases, Centre of Cardiology and Angiology, Lithuania Introduction: Physical activity is associated with improved health outcomes for adolescents. Many of the benefits are observed with an average of at least 60 min of moderate-to-vigorous intensity physical activity daily (1). Unfortunately, more than 80% of school-going adolescents did not meet current recommendations for daily physical activity (2). Objective: We aim to analyze physical activity trends and their association with stress, weight, screen time, and other factors in Lithuania adolescents. Methods: A prospective observational cross-sectional study enrolled students from High Schools in Lithuania's capital city. A survey was administered to a cohort of students aged 13-18 years. Data from a questionnaire about behavioral risk factors, academic performance, stress level at school, and physical activity were collected. Stress levels were measured by 10 points system. Data were analyzed using SPSS v28 statistical package. Results: The study population consisted of 589 adolescents (61.4% female and 38.5% male participants). The mean age was 15.79 +- 2.81 years. Adolescents engage in physical activity for 3.30 +- 1.91 days a week. Only 18.34% of adolescents' (12.98% female vs 26.87% male; p < 0.001) physical activity lasts more than 420 min a week (60 min daily). Adolescents who exercise more, experience less stress at school (p < 0.001). Whereas screen time lasts 6.80 +- 3.23 hours daily and is associated with higher stress levels at school (p < 0.001). Smoking and alcohol consumption were significantly more common among girls (smoking: 22,37% vs 22,70%; p = 0,632; alcohol: 27.73% vs 21,15%; p < 0.001). Conclusions: More than 80% of adolescents in Lithuania did not meet recommendations for daily physical activity. Girls are less active than boys and tend to have more addictions. To avoid health consequences, it is necessary to strengthen education about cardiovascular risk factors and a healthy lifestyle benefits. 110978 Modality: E-Poster Researcher - Non-case Report Category: CARDIO-ONCOLOGY Effect of Exercise on Cardiorespiratory Capacity After Bone Marrow Transplantation in Oncohematologic Patients: A Pilot Study LOURENCO SAMPAIO DE MARA1, Mariana Kleis Pinto da Luz Lodi3, Suellen Cristina Roussenq3, Magnus Benetti2 (1) Curso de Pos Graduacao em Cardio-Oncologia SBC/INC/INCA, Rio de Janeiro, RJ, Brasil; (2) Universidade do Estado de Santa Catarina-UDESC Centro de Ciencias da Saude e do Esporte - CEFID, Nucleo de Cardioncologia e Medicina do Exercicio Santa Catarina, SC, Brasil,; (3) Centro de Pesquisas Oncologicas - CEPON, Santa Catarina, SC, Brasil Introduction: Bone marrow transplantation (BMT) remains the best clinical alternative for the treatment of leukemias and chemotherapy-refractory lymphoid cancers. There is an increase in the survival of these patients, but with cardiovascular sequelae, which can be minimized by the effects of exercise. Objective: To analyze the effect of exercise on the gain of cardiovascular capacity in patients undergoing allogeneic BMT. Methods: Pilot study of a randomized controlled clinical trial with the Brazilian Registry of Clinical Trials, registry RBR-887gqvs. Fifteen patients with leukemia and lymphoma who were eligible for BMT participated, nine were randomized to the exercise intervention group (EIG), and six to the control group (CG). The EIG performed aerobic and resistance exercise during hospitalization, followed by a cycle ergometer protocol at Day Hospital, three times a week until the 100th day after BMT, with assessments of cardiovascular capacity by the six-minute walk test, which occurred before BMT or time 1 (T1), at hospital discharge or time 2 (T2) and 100 days post BMT or time 3 (T3). Data were evaluated using the SSPS software version 20.0. Results: The mean age of patients in the EIG was 38.7 (+-8.7) years with 78% men and for the CG, 41.7 (+-15.4) years with 50% men, with no difference between the groups (p = 0.860). In the comparison between EIG and CG regarding cardiorespiratory functional capacity, there was no difference in T1 (727.5 +- 160 x 640 +- 209; p 0.232) and in T3 (885 +- 379.1 x 790 +- 162.8; p 0.794) and an increase in functional capacity in favor of the EIG in T2(813.7 +- 192 x 530 +- 209.3; p 0.009). Comparing the distances covered with the predicted value within the groups, it was observed that the EIG covered distances significantly greater than the predicted in the three different times: T1 (598.9 +- 39.7 x 727.5 +- 164.9; p = 0.038); T2 (598.9 +- 39.7 x 813.7 +- 192.7; p = 0.011); T3(598.9 +- 39.7 x 885 +- 379.1; p = 0.039). The CG covered a greater distance than predicted only in T3 (578.5 +- 21.9 x 790 +- 162.8; p = 0.046). There was no significant difference between the average distance covered predicted for the EIG and the CG (598.9 +- 39.7 x 578.5 +- 21.9; p = 0.131). Conclusion: Patients who perform an exercise program during and after hospitalization for allogeneic BMT benefit from a gain in cardiorespiratory capacity. 110982 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Impact of a Specialized Heart Failure Therapeutic Protocol In-Hospital Outcome and 30-Day Readmission in Patients with Acute Heart Failure MARCELO WESTERLUND MONTERA1, Louise Freire1, Fabiola Traverso1, Beatriz Robert1, Isaura Rocha1, Daniele Cordeiro1, Ana Maria Medeiros1, Ana Amaral Dutra1 (1) Hospital Procardiaco Introduction and/or Fundamentals: The treatment of acute decompensated heart failure (ADHF) in clinical practice is usually carried out by a cardiologist not specialized in heart failure (HF). The implementation of specialized HF protocols (HFP) in the treatment of ADHF has shown benefits in improving the outcomes and quality of care. Objectives: To assess the benefits of HFP versus usual care(UC) in patients with ADHF in terms of clinical outcomes in in-hospital mortality(IHM), length of stay(LS), and readmission at 30 days(R30d), and the quality of care through the analysis of the medication prescription rate at hospital admission and discharge. Materials and methods: Retrospective non-randomized study of a cohort of 834 pts with ADHF and HFrEF(LVEF < 50%) admitted to a private hospital in Rio de Janeiro, between 01/2015 and 12/2021 381 pts were submitted to HFP and 453 pts to the UC defined by the attending physician. All pts were evaluated for their clinical characteristics, LVEF by echocardiogram, natriuretic peptide levels. The outcomes evaluated were:LS, IHM and R30d. The rate of prescription of beta-blockers (BB) and converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) and spironolactone(spiron.) were also evaluated at hospital admission and discharge. Results: There was no significant difference between the groups in terms of age, sex, ADHF etiology, systolic blood pressure at admission, BNP and NT-proBNP levels and LVEF. HFP pts had a lower rate of IHM(11% vs 20%;p < 0.0001), and LS(7.4 +- 6.9 vs 10.5 +- 12.8 days;p < 0.001), and with no significant difference regarding R30d (4.3% vs 7.2%; p = 0.2). At admission the HFP pts showed a higher rate of ACEI/ARB prescription (45% vs 36%; p < 0.006) and higher dosage of intravenous furosemide (120 +- 60 mg vs 60 +- 30 mg, p < 0.01) and no difference in BB prescription rate(75% vs 70%; p < 0, 15). At discharge, the HFP pts had a higher rate of prescription of ACEI/ARB (89% vs 43%; p < 0.0001) and spiron. (50% vs 27%; p < 0.0001) and furosemide(72% vs 62% p = 0.05) and no difference in BB prescription rate(87% vs 84%; p = 0.2). Conclusions: The treatment of pts with ADHF with HFP compared to UC, had an impact on improving in-hospital clinical outcomes with lower IHM and LS and they also had a better quality of care with a higher rate of prescription of ACEI/ARB and higher dosage of intravenous furosemide at admission, and a higher rate of prescription of ACEI/ARB, spiron. and furosemide at hospital discharge. 110986 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Differential Diagnosis between Takotsubo Cardiomyopathy and Acute Myocardial Infarction at Hospital Admission MARCELO WESTERLUND MONTERA1, Louise Freire1, Arnaldo Rabischoffsky1, Amarino de Oliveira1, Luiz Antonio Carvalho1, Ana Amaral Dutra1 (1) Hospital Procardiaco Objectives: Identify the clinical characteristics and complementary tests that allow the differentiation of Takotsubo from Acute Myocardial Infarction (AMI) with ventricular dysfunction, at hospital admission. Materials and methods: Retrospective study of a cohort of patients admitted to a private hospital in Rio de Janeiro, from 2010 to 2020, with a diagnosis of Takotsubo and AMI with ventricular dysfunction (LVEF < 40%). The variables evaluated were: 1) clinical characteristics: age, gender, clinical presentation, presence of decompensating factor (DF), systolic blood pressure (SBP) and heart rate (HR). 2) ECG changes: T wave inversion, ST segment changes, pathological Q wave; 3) changes in the echocardiogram (ECO) regarding the location and type of segmental contraction 4) Levels of TpI, BNP, NT-proBNP, leukocytes and CRP. All patients initially underwent coronary angiography. The t test for independent samples, chi-square and logistic regression were used. Results: 65 pts were evaluated with Takotsubo and 75 pts with AMI. There were no differences between the groups regarding age, clinical presentation, SBP and HR. There were also no differences regarding the levels of BNP and NT-proBNP, TpI, leukocytes and CRP at admission. Pts with Takotsubo had a higher prevalence of females (84.6% vs 13.8%, P < 0.0001) and identification of a DF in 78% of Takotsubo pts. The ECG in the pts with Takotsubo showed a higher prevalence of T wave inversion (38% vs 12.5%; p = 0.0005) with no differences in the other ECG alterations compared to the pts with AMI; The ECHO of the pts with Takotsubo showed a higher prevalence of akinesia in Apical (69% vs 32%; P < 0.001), anterior (23% vs 5.5%; P < 0.003) and Lateral (32% vs 2.7%, P < 0.0001)walls. In the logistic regression, the variables that showed high significance and predict the diagnosis of Takotsubo were:female (OR:9.8;CI:3.1-30.8); T wave inversion on ECG(OR: 5.8; CI: 1.45 to 23.71); Apical (OR:36.12;CI:4.8-271.7) and Anterior akinesia (OR:17.3;CI:2.8-109.8) on ECHO. Conclusoes: In the differential diagnosis of Takotsubo from AMI on hospital admission, the presence of female Pts, with DF, T-wave inversion on ECG, anterior or apical akinesia on ECHO, strongly suggest the diagnosis of Takotsubo in the face of AMI with ventricular dysfunction. 110998 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Microrna in the Cardiac Variant of Fabry's Disease: New Biomarker? ANDREA VIRGINIA FERREIRA CHAVES1, Debora Nascimento da Nobrega3, Marcelo Santos Veloso4, Eveline Barros Calado5, Manuel Markman2, Anabel Lima Vieira2, Milca Dantas da Silva1, Brivaldo Markman Filho5, Luydson Richardson Silva Vasconcelos3, Dinaldo Cavalcanti de Oliveira5 (1) Rarus - Servico de Doencas Raras de Recife; (2) Hospital Agamenon Magalhaes, Recife, PE; (3) Instituto Aggeu Magalhaes; (4) Hospital Alfa, Recife; (5) Universidade Federal de Pernambuco - UFPE Introduction: Molecular investigation of hypertrophic cardiomyopathy (HCM) through genetic panels makes it possible to identify phenocopies with left ventricular hypertrophy (LVH), as Fabry disease (FD). New biomarkers are being studied, including microRNAs (miRNAs). Objective: To investigate miRNAs as pathogenicity markers in the cardiac variant of FD. Methods: A total of 131 patients (pts) with HCM who underwent genetic investigation for FD were included, of which 76 were through GLA sequencing gene and 55 by the genetic panel for HCM. Results: In 7 pts (5.34%) mutations were found in the GLA gene and the following variants were identified: 1 c.967C>A(p.Pro323Thr), 4 c.352C>T(p.Arg118Cys) and 2 c.937G>T(p.Asp313Tyr). Pts with mutations in the GLA gene were submitted to the panel for HCM: 3 pts (p.Arg118Cys) had mutations in other genes and in 4, there were no other detecting variants. The family screening revealed 17 individuals with mutations in the GLA gene, and 2 siblings were identified with LVH with the c.937G>T(p.Asp313Tyr) variant. The pts and the carriers of variants in the GLA gene were submitted to the determination of lyso-Gb3 and the analysis of the following miRNAs: miR-1291, miR-214, and miR-505. In the comparison between individuals with and without LVH, there was no significant difference for miRNAs, however, there was a tendency for overexpression in individuals with LVH, especially for miR-1291. The expression of miR-214 in subjects with LVH was significantly lower than in subjects without LVH (p = 0.0416). There was a significantly higher expression for miR-505, both in carriers of variants in the GLA gene without LVH and in those with LVH (p = 0.0195). The miR-505 and miR-214 showed a significant and directly proportional correlation with lyso-Gb3 in pooled pts (with and without LVH). All subjects had normal lyso-Gb3 levels. Conclusion: In this study, provides evidence that increased miR-505 and miR-1291 expression and miR-214 under-expression in those with LVH may be pathogenic markers in FD. Further investigations of these microRNAs with a larger number of individuals are necessary. 111032 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Femoral Arterial Puncture Guided by Fluoroscopy Versus Puncture Guided by Anatomical Parameters Alone: A Prospective Randomized Clinical Trial INGRID LOUREIRO DE QUEIROZ LIMA1, RICARDO ZAUTIH SILVA1, FABIO AUGUSTO PINTON2, JOSE MARIANI JUNIOR3 (1) HOSPITAL IRMANDADE SANTA CASA DE SAO PAULO; (2) HOSPITAL SIRIO LIBANES; (3) HOSPITAL ISRAELITA ALBERT EINSTEIN Objective: To evaluate whether puncture guided by fluoroscopy was more effective for accessing the common femoral artery (CFA) than puncture guided by anatomical parameters alone. Background: Although radial vascular access is becoming the preferred route of access for most procedures in interventional cardiology, CFA remains the major vascular access used in practice. Properly accessing the femoral artery reduces the incidence of vascular complications; however, in some cases, the anatomical parameters may not adequately guide the appropriate route of access to the CFA. Methods: Single-center, prospective, controlled, randomized study, performed between June and December of 2015, evaluated 158 patients subjected to elective coronary angiography guided by fluoroscopy or angiography guided by classical anatomical parameters alone. In all patients, angiography was performed at the site of vascular access and was considered appropriate if the access route to the CFA was above the bifurcation of the CFA and below the inferior epigastric artery. Results: Seventy-nine patients underwent puncture guided by anatomical parameters alone, and 79 underwent puncture guided by fluoroscopy. Puncture guided by fluoroscopy achieved greater success rates than did the use of anatomical parameters alone (92.4% vs. 64.6%; p < 0.001). In all groups analyzed, the one guided by fluoroscopy had more appropriate punctures than did the group using anatomical parameters alone. The independent predictors of inadequate puncture were age > 65 years and puncture guided by anatomical parameters alone. Conclusions: Puncture guided by fluoroscopy increased the likelihood of adequate access to the CFA compared with puncture guided by anatomical parameters alone. 111048 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Correlation between Carotid Artery Disease (CAD) and Peripheral Arterial Disease (PAD) PALJOSKOVSKA JORDANOVA SAVETKA1, D-r Danica Petkoska Spirova1, D-r. Sasha Kjaeva Anastasova1, D-r Dejan Risteski1, D-r Emilija Lazarova Trajkovska1, D-r Enes Shehu1, D-r Aleksandra Eftimova1, Prof. D-r Marijan Bosevski1 (1) University Clinic of Cardiology Introduction: Peripheral arterial disease (PAD) is a condition in which the arteries are narrowed and they can't carry as much blood to the outer parts of the body. Carotid artery disease (CAD) causes a narrowing of the major blood vessels that supply the brain. Both are known to be specific manifestations of atherosclerosis. We aimed to evaluate patients with documented CAD who also have PAD and investigate the risk factors that should be considered when talking about these vascular diseases. Material and methods: This study included a population of 1031 patients with documented carotid artery disease is defined as a presence of plaque or stenosis confirmed with B-mode ultrasonography. 66,6% were men and 33,5% were women. The average age was 64.44 years. We investigate how many patents with CAD have PAD and evaluate the potential risk factors. Results: This analysis reveals that 1030 out of 1031 patient (99,9%) have CAD and 1023 out of 1031 patient (99.2%) also has PAD. The most common risk factor is HTA in 1026 patients or 99.5% followed by diabetes mellitus in 1025 patients or 99.4%, tobacco smoking in 958 patients or 92.9%, HLP in 958 patients or 86.8% and also obesity found in 351 patients or 34%. Conclusion: PAD is strongly associated with carotid artery disease. According to our study, these diseases seem to occur more commonly in men that women. We can conclude that the most prevalent factors that can influence the risk of developing an outcome are hypertension and diabetes mellitus. In accordance with this, these patients need more intensive medical management to prevent complications. 111244 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Acute Coronary Syndrome During COVID-19 Pandemic: What Changed? a Single Center Retrospective Database CONRADO ROBERTO HOFFMANN FILHO1, Conrado Roberto Hoffmann Filho1, Benjamin Massao Harada1, Joao Paulo Souza Brighenti1, Michele Mendonca1, Beatriz Roca1, Gilmar Sidnei Erzinger2, Esther Botelho1, Gabriel Erzinger2, Jaqueline Barp1, Joao P.P. Ribeiro2 (1) Hospital Regional Hans Dieter Schmidt; (2) Univille Universidade da Regiao de Joinville Introduction: Acute myocardial infarction remains the leading cause of death in Brazil and worldwide with high mortality rates, especially when adequate treatment is not performed. During the period of the COVID-19 pandemic, the demand for care services caused by acute coronary syndromes (ACS) was reduced by several factors. Objetives: The present study was carried out to evaluate the management of our institution in the treatment of ACS during the COVID-19 pandemic. Methods: Retrospective cohort study of patients treated at a tertiary center from 01/01/21 to 01/31/21, through the analysis of hospital's electronic medical records. 582 patients were selected. SPPS software was used. Student's T test to compare numerical variables. Categorical variables were expressed as frequencies and percentages and compared using the chi-square test. Pearson's correlation used as needed. Quantitative variables were expressed as mean and standard deviation. Results: Mean age did not differ between men and women 62.1% and 62.8% respectively. The ACS were divided in unstable angina (UA) in 30.6% and 32.1%, Non ST Elevation Myocardial Infarction (NSTEMI) 36.5% and 31.5% and ST elevation myocardial infarction (STEMI) 32.3% and 36.2%. Among coronary lesions >70%, Left anterior descending 61.4% and 64.1%, right coronary 45.6% and 49.3%, circumflex 28.9% and 35.8%, left main >50% 1.1% and 6.3%. The presence of left main lesion was higher in men. Significant positive correlation was observed between age and left descending lesion p = 0.04. In-hospital death was greater among older (67.7 and 61.9 years respectively) p = 0.003. Despite the number of deaths being significantly higher (p = 0.001) in STEMI (4.6%) compared to NSTEMI (2.4%) and UA (0.5%), the mean age was significantly lower in the first p = 0.03. Angioplasty was the most used treatment with 68.2% of cases and myocardial revascularization in 5%, p = 0.0005. Regarding treatment, about 87% used ASA, 80% antiplatelet drugs, statins 88%, ACEI/ARB 88.9% beta-blockers 85.6%, spironolactone 16.5% and insulin 8.6%. Comparing our data with literature, we found that the in-hospital mortality rate is similar (7.6%), the mean age is lower (62% and 68% respectively). The number of coronary angioplasty is higher (68.2% and 38.5%). And the number of revascularizations is lower (5% and 7.8% respectively). Conclusions: The pandemic reduced the number of patients who went to the hospital, however the standard treatment of ACS was maintained. 111065 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS In-Hospital Mortality Risk Predictors of Acute ST-Elevation and Non-ST-Segment Elevation Myocardial Infarction RICARDO MOURILHE-ROCHA1, Daniel Xavier de Britto Setta1, Marcelo Luiz da Silva Bandeira1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Eric Costa de Almeida1, Julia Paulo Mourilhe Rocha1, Bruno Reznik Wajsbrot1, Roberta Siuffo Schneider1, Ricardo Mendes Carneiro1, Vitor Hugo Mussi Campos1, Fernando Oswaldo Dias Rangel1 (1) HOSPITAL PRO-CARDIACO Background: Acute myocardial infarction is a prevalent disease with high morbidity and mortality. The recognition of mortality predictors allows the identification of patients at higher risk of death. Objective: To identify the risk predictors of in-hospital mortality. Materials and Methods: Observational, retrospective, cohort study of 398 patients admitted with a confirmed diagnosis of AMI, with and without ST-segment elevation (STEMI and NSTEMI) between January 2018 and January 2022. Data were subsequently analyzed by SPSS software. Results: Among the comorbidities analyzed, mortality in the presence of previous diseases was heart failure (HF) occurred in 20.6% and 6.3% in those without HF (p = 0.03); previous stroke (stroke) in 21.4% and without stroke of 6.5% (p = 0.04); with atrial fibrillation (AF) 22% and without AF in 5.9% (p < 0.01). The mortality found in patients with different characteristics was: Killip I was 2.5% and in Killip >= 2 was 31.7% (p < 0.001); EF > 50% was 1.2% and EF <= 50% was 14% (p < 0.001); STEMI was 13.7% and NSTEMI was 4.7% (p = 0.02); without angioplasty was 13.3% and with angioplasty was 6.1% (p = 0.027). Binary logistic regressions were performed to check if such factors are independent predictors of risk, being statistically significant: ejection fraction <50%, OR 6.2 95% CI (1.6-23.6), p = 0.007; and Killip classification >= 2, 95% CI (3.0-25.7), p < 0.001. Conclusions: The predictors of mortality were the presence of EF <= 50% and Killip >= 2. Such factors are related to the extent of myocardial injury caused by AMI and the presence of previous heart disease. Early recognition of these circumstances may allow the development of care aimed at reducing this outcome. 111071 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Whole-Body Vibration Exercise in the Management of Cardiovascular Diseases: A Systematic Review ANA INES GONZALES1, Ana Ines Gonzales1, Amanda da Silva1, Gabriella Lavarda do Nascimento1, Mario Bernardo-Filho2, Danubia da Cunha de Sa-Caputo2, Anelise Sonza1 (1) Universidade do Estado de Santa Catarina (UDESC) - Centro de Ciencias da Saude e do Esporte (CEFID); (2) Universidade do Estado do Rio de Janeiro Introduction: In the management of cardiovascular diseases (CVD), the adequate exercise prescription is an essential condition. In this scenario, the whole body vibration exercises (WBV) appear as a promising therapeutic resource. Objective: To investigate the effects of WBV alone or associated with other types of exercises in the management of CVD. Methods: This study is a systematic review following the PRISMA guidelines and registered PROSPERO under number CRD42021230663. The databases used were PubMed, Cochrane, PEDro, Lilacs, and Science Direct, from the beginning of the databases until January 2021. The descriptors related to WBV and CVD used were: [(Hypertension OR Heart Diseases OR Heart Failure OR Coronary Artery Disease OR Myocardial Infarction) AND (Whole Body Vibration OR Whole-Body Vibration)]. The following inclusion criteria were determined:studies such as controlled and randomized clinical trials, quasi-randomized controlled trials, comparative studies with or without simultaneous controls, case studies, case series with ten or more consecutive cases, cross-sectional studies, and pilot studies. The population was composed by adults (>=18 years), of both sexes, with a clinical diagnosis of CVD, submitted to intervention with the exercise of WBV. Studies in Portuguese, English, and Spanish were included. The selected studies were assessed for quality, risk of bias, and level of evidence. Results: Three studies were included, with CVD submitted to WBV as an isolated intervention (35 females/12 males). There was variation in the parameters applied in the WBV. There were no abnormal cardiovascular responses in the three studies, and no adverse events were reported. The reactive hyperemia index (RHI) showed a significant increase after WBV in several subgroups and the muscle strength measure showed a significant increase in muscle strength when compared to the control group in the two studies. There were improvements in the parameters of systolic and diastolic blood pressure, pulse pressure, augmented pressure, augmentation index, AIx adjusted to 75 beats per minute, first systolic and second systolic peak and mean arterial pressure. Conclusion: The use of different IVC protocols, alone, to improve hemodynamic, cardiovascular, vascular/arterial and muscular parameters in individuals with CVD is plausible and can be considered a safe and effective training resource. 111077 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Implementation of a Home-Based Cardiac Rehabilitation Program in Brazil: An Effectiveness Analysis ANA INES GONZALES1, Ana Ines Gonzales1, Yolanda Goncalves da Silva Fontes1, Daiane Pereira de Lima1, Tatiane Boff Centenaro1, Tales de Carvalho1 (1) Universidade do Estado de Santa Catarina (UDESC) - Centro de Ciencias da Saude e do Esporte (CEFID) Introduction: Cardiac Rehabilitation is considered an effective strategy in the treatment of individuals with Cardiovascular Diseases and has substantive evidence base on its benefits. However, in Brazil there is a predominance of programs based on rehabilitation centers that provide access to a minority of patients, providing low adherence to rehabilitation. Given this situation, alternative models are plausible to be tested, with home-based CR being a possibility to expand access and adherence of individuals. Objective: To compare adherence, quality of life (QoL), functional capacity and perception of barriers in patients undergoing center-based (CB) and home-based (HB) CR. Methods: Individuals with Coronary Artery Disease, randomized into two groups (CB and HB), were submmited to a 12 week of aerobic aerobic training with walking and patient education. Exercise prescription was individualized, based on heart rate (HR) determined by the ventilatory thresholds of the cardiopulmonary exercise test. In all, 36 physical exercise sessions were proposed. The sessions in the CB group were all supervised and monitored in person and in the HB only 3 supervised (one per month) and 33 at home (streets, squares, parks), with remote monitoring and monitoring (asynchronous). Adherence to sessions was evaluated by the average percentage of sessions performed. QOL and functional capacity were measured before and after 3 months using Short Form 36 and peak oxygen consumption, respectively. Barriers were verified after 3 months by the Scale of Barriers for CR (EBRC). Results: 21 (32.3%) individuals participated in the study, distributed in CB (N = 11) and HB (N = 10). HB showed higher adherence in the number of prescribed sessions (p < 0.001) and extra sessions (p = 0.001). Regarding QoL, only a significant intergroup difference was observed. In the HB group, in the domains of functional capacity (p = 0.04), limitations due to physical aspects (p = 0.04) and emotional aspects (p = 0.04). In the CB group, regarding the functional capacity domains (p = 0.01) and limitations due to physical aspects (p = 0.01). There was no difference between groups and between groups for peak VO2 values. Regarding the perception of barriers, the CB group had the highest total score (p < 0.01). Conclusions: HB adherence was higher, with better results in the emotional aspect of QoL and lower perception of barriers. 111076 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Quality of Care: Getting with the Guidelines in Patients Hospitalized with Acute Myocardial Infarction DANIEL XAVIER DE BRITTO SETTA1, Marcelo Luiz da Silva Bandeira1, Bruno Reznik Wajsbrot1, Julia Paulo Mourilhe Rocha1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Claudia Lanzillotti Weksler1, Roberta Siuffo Schneider1, Ricardo Mendes Carneiro1, Vitor Hugo Mussi Campos1, Fernando Oswaldo Dias Rangel1, Ricardo Mourilhe-Rocha1 (1) HOSPITAL PRO-CARDIACO Background: Acute myocardial infarction (AMI) is a prevalent disease with high morbidity and mortality. The measurement of quality indicators in health care enables the recognition of weaknesses and the construction of action plans to improve care. One of the main indicators is the utilization rate of survival modifying medications at the time of hospital discharge, whose internationally recommended goal is at least a 90% utilization rate. Objectives: To evaluate the rate of use of survival modifying drugs in AMI care [ASA, P2Y12 inhibitors, beta-blockers, statins and iECA or ARB (the latter in the presence of ventricular dysfunction) at hospital discharge]. Methods: This is an observational, retrospective, cohort study of 398 patients admitted with a confirmed diagnosis of AMI with and without ST-segment elevation between January/2018 and January/2022. Data were collected by a trained healthcare professional team and subsequently analyzed by SPSS software. Results: The diagnosis of STEMI (68.8%) was predominant. Drug utilization rates at discharge in the general population and subgroups were: AAS = 96.9% (97.6% in NSTEMI and 95.2% in STEMI; p = 0.23), P2Y12 inhibitors = 93.5% (93.9% in NSTEMI and 92.5% in STEMI; p = 0.59), beta-blockers = 86.9% (81.3% in NSTEMI and 83.8% in STEMI; p = 0.4), iECA or ARB = 82.9% (71.0% in NSTEMI and 60.0% in STEMI; p = 0.23), statins = 93.8% (93.5% in NSTEMI and 94.3% in STEMI; p = 0.79). Conclusions: The ASA, P2Y12 inhibitor, and statin utilization rates were within the recommended target. However, the usage rates of beta-blockers and ACEI or ARB were lower. The recognition of these indicators allows the initiation of strategies to expand the use of these drugs and improve outcomes in the medium and long term. 111102 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Spirituality/Religiosity in the Cardiology Outpatient Clinic: How are we 02 Years After the Publication of the Updated Cardiovascular Prevention Guideline of the Brazilian Society of Cardiology (Spirituality and Health)? ADELLE CRISTINE LIMA CARDOZO1, Jose Icaro Nunes Cruz1, Giulia Vieira Santos1, Jade Soares Doria1, Camille Marques Aquino1, Juliana Maria Chianca Lira1, Philipi Santos Soares1, Diego Maldini Borba de Lima1, Mariano Cesar de Souza Reis1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital; (3) Primavera Hospital Introduction: Several studies analyze the influence of Spirituality/Religiosity (S/R) on cardiovascular diseases, considered the leading causes of global morbidity and mortality. The brazilian Updated Cardiovascular Prevention Guideline (2019) shows the importance of S/R in healthcare and recommends its approach in clinical practice. Objectives: To describe the clinical profile and S/R in cardiology patients and to evaluate the acceptance of the S/R approach during the medical consultation. Methods: Cross-sectional, descriptive study. The sample included patients from cardiology outpatient clinics of three hospitals in Sergipe (Brazil). A questionnaire of self elaboration and two scales were applied: Duke Religiosity Index (DUREL) and Brief Multidimensional Measure of Religiosity/Spirituality (BMMRS). The values obtained in the constructs and domains of the scales were entered into the database so that they scored directly proportional to the level of S/R. Results: 130 patients were included in the study (mean age 60.6 +- 11.2 years). 62.3% were female. The prevalences of hypertension, dyslipidemia, coronary artery disease, and diabetes mellitus were 73.8%, 59.2%, 40.8%, and 35.4%, respectively. 97.6% of the patients believe in God and 79.8% believe that S/R helps to cope with the diseases. 96.9% would like to have S/R addressed in a doctor's appointment, however 78.1% stated that this topic was never addressed by their doctors. 96.9% said they were Christian (76.2% Catholic, 19.8% Evangelical, and 2.4% Spiritualist), 3.8% said they had no religion, and 0.8% were Umbanda believers. The domains with the highest mean scores on the BMMRS were "Values and Beliefs" (7.1 +- 1.2; scale maximum: 8.0) and "Religious and Spiritual Overcoming" (25.0 +- 2.9; scale maximum: 28.0). The means of the constructs organizational religiosity, non-organizational religiosity, and intrinsic religiosity (DUREL) were 4.1 +- 1.5, 4.6 +- 0.8, 13.8 +- 2.1, respectively, all of them considered high. Conclusions: Cardiology patients had a high level of religiousness in this study. Almost the totality of the sample believed that S/R should be addressed during medical consultations. Despite this, most stated that their physicians never addressed these topics during consultations, denoting a mismatch between clinical practice and the recommendation of the Guideline. 111090 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Predictors of Mortality in Patients Hospitalized for Acute Atrial Fibrillation RICARDO MOURILHE-ROCHA1, Bruno Reznik Wajsbrot1, Ricardo Mendes Carneiro1, Eric Costa de Almeida1, Julia Paulo Mourilhe Rocha1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Claudia Lanzillotti Weksler1, Ana Amaral Ferreira Dutra1, Tiago Azevedo Costa Mattos1, Fernando Oswaldo Dias Range1, Daniel Xavier de Britto Setta1 (1) HOSPITAL PRO-CARDIACO Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. Epidemiological data have shown that AF is a huge public health problem due to its association with a high risk of death and functional loss. Characterizing mortality predictors allows identifying patients at higher risk for evolution to death. Objective: To identify risk predictors for in-hospital mortality in patients with atrial fibrillation. Methods: Retrospective and consecutive cohort of patients hospitalized for acute atrial fibrillation between January 2018 and December 2021 at a tertiary hospital in Rio de Janeiro. Demographic, clinical, laboratory and mortality data were analyzed, obtained from a database collected by reviewing electronic medical records and subsequently performing univariate and multivariate statistical analysis using SPSS 20.0. Results: There were 819 patients, with a male predominance (57.6%), mean age of 71 +- 14.4, 72.6% aged >65 years, 66.4% hypertensive, 21.7% diabetic, 12% with HF, 8.2% with stroke or previous TIA, 21.6% with previous coronary artery disease and 8.6% with CABG surgery. The median of CHA2DS2-VASc was 3 and the median of HASBLED was 2. There was reversion to sinus rhythm in 69.9% of the patients. The general mortality of the population was 0.9%. Mortality in patients with CHA2DS2-VASc >= 3 was 1.2% vs 0 in those with CHA2DS2-VASc <3 (p = 0.02). In patients with CHA2DS2-VASc >= 2 or +, 0.9% died vs no death in patients with CHA2DS2-VASc <2 (p = 0.092). Analyzing the VASc variables (from CHA2DS2-VASc), if variables are present it increases mortality by more than 3 times (0.5% vs 1.8%; p = 0.071). Another important parameter was age >= 75 years, which almost triples mortality (0.5% aged < 75 years vs 1.3% aged >= 75 years (p = 0.193). All other variables showed no relationship to the mortality. Conclusion: The only predictor of mortality in this population was CHA2DS2-VASc >= 3. Early recognition of higher-risk patients can provide a more targeted care plan aimed at early discharge without increasing negative outcomes. 111113 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Spirituality/Religiosity and Resilience in Patients with Chronic Coronary Syndrome ADELLE CRISTINE LIMA CARDOZO1, Jose Icaro Nunes Cruz1, Jade Soares Doria1, Camille Marques Aquino1, Gabriela de Oliveira Salazar1, Bruna Souza Matos de Oliveira1, Diego Maldini Borba de Lima1, Giulia Vieira Santos1, Juliana Maria Chianca Lira1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital; (3) Primavera Hospital Introduction: Despite advances in treatment, chronic coronary syndrome (CCS) persists as an important cause of global morbidity and mortality worldwide. Spirituality/Religiosity (S/R) has been pointed out as an important dimension in health care, including cardiovascular diseases. Objectives: To evaluate S/R in patients with CCS and its association with Resilience. Methods: This is an observational, cross-sectional, analytical study. The sample included patients from cardiology outpatient clinics of three hospitals in Sergipe. The patients included were divided into two groups: I) CCS; II) Control. Three questionnaires were applied: Duke Religiosity Index (DUREL); Brief Multidimensional Measure of Religiosity/Spirituality (BMMRS), and Connor-Davidson Resilience Scale for Brazil-10. The scales were quantified ordinally according to the progression of the degree of S/R, so that the higher the average on the scale, the higher the level of S/R. Mean scores on the scales were compared using Student's t-test. Demographic characteristics and comorbidity profile were described in terms of means and frequencies and compared between groups using the Chi-square or Fisher's exact test. Results: Were included 130 patients, of whom 53 (40.8%) belonged to the CCS group and 77 (59.2%) to the Control group. Ages were not different between the CCS and Control groups (62.2 vs. 59.4 years; p > 0.05). There was also no difference between the groups for the following variables: marital status, work status, diabetes mellitus, hypertension, sedentary lifestyle, and obesity (p > 0.05), however, dyslipidemia was more prevalent in the CCS group (80.0% vs. 50.7%; p < 0.001). According to the BMMRS, patients in the CCS group believe that "God punishes them" more than control patients (3.1 vs. 3.5; p < 0.05). In addition, the CCS group believed that "people in their religious communities would offer them less comfort in difficult times" than patients in the Control group (2.8 vs. 3.2; p < 0.05). There were no differences between the groups for the DUREL or the Resilience Scale. Conclusions: The results suggest that patients with CCS are more likely to believe that "God punishes them" and that "people from their religious communities would offer them less comfort in difficult times". There was no correlation between S/R and Resilience. Studies with larger sample sizes are needed to better understand this last association. 111123 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Importance of Chloride in Chronic Heart Failure MARTA AMORIM1, Diana Ferrao1, Marta Carreira1, Fernando Nogueira1, Pedro Ribeirinho Soares1, Sergio Madureira1, Rita Gouveia1, Catarina Elias1, Ana Neves1, Joana Pereira2, Patricia Lourenco3 (1) Heart failure clinic of the Internal Medicine Department of Centro Hospiralar e Universitario Sao Joao; Faculdade de Medicina da Universidade do Porto; (2) Heart failure clinic of the Internal Medicine Department of Centro Hospiralar e Universitario Sao Joao; (3) Heart failure clinic of the Internal Medicine Department of Centro Hospiralar e Universitario Sao Joao; Cardiovascular Research and Development Unit of Faculty of Medicine of Porto University Introduction: Low Chloride (Cl) has been associated with worse prognosis in heart failure (HF). Still, results are controverse and mainly based in old Randomized controlled trials. Objectives: To assess determinants of Cl levels and to study the prognostic role of Cl in a contemporary real-world chronic HF population. Methods: Retrospective analysis of chronic ambulatory HF patients followed in a HF clinic. Adult patients with history of HF with left ventricular systolic dysfunction (LVSD) attending the clinic between January 2012 and May 2018 were included. Patients with no Cl measurement were excluded. Follow-up: until February 2022. Primary endpoint: all-cause mortality. Multivariate linear regression analysis to assess independent determinants of Cl level. The prognostic impact of Cl was evaluated by Cox-regression analysis. Cl was assessed both as a categorical (cut-off 101 mmol/L - percentile 33.3) and as a continuous variable. Multivariate adjustment was performed accounting for: age, gender, LVSD, NYHA class, arterial hypertension, diabetes, atrial fibrillation, ischaemic aetiology, BNP, renal function, serum sodium, loop and thiazide diuretics and evidence-based therapy. Results: We studied 859 patients. Mean age 70 years, 66.3% male, 44.9% had ischaemic HF and 46.7% had severe LVSD; 84.3% were on renin-angiotensin system inhibitors (RASi), 92.8% on beta blockers and 29.1% on mineralocorticoid receptor antagonists. Cl ranged from 85 to 116 mmol/L. Independent determinants of decreased Cl levels were Diabetes, severe LVSD, higher NYHA class and lower natremia. RASi medication associated with higher Cl and loop and thiazide diuretics predicted lower serum Cl. During a median follow-up of 56 (29-90) months 464 (53.4%) patients died: 45.9% in those with Cl > 101 mmol/L and 66.6% in the remaining, p < 0.001. Patients with Cl <= 101 mmol/L) had a multivariate adjusted HR of death of 1.27 (95% CI 1.02-1.57), p = 0.03 compared to those with higher Cl. Per each 2 mmol/L increase in Cl levels the all-cause death HR was 0.94 (95% CI: 0.89-1.00), p = 0.048. Conclusions: Low Cl is an independent predictor of all-cause mortality in HF with LVSD. Patients with Cl <= 101 mmol/L have a 27% increased risk of death and per each 2 mmol/L Cl increase there is a 6% decrease in the death risk. Main determinants of lower Cl are diuretic use, concomitant diabetes, worse LVSD and higher NYHA class; use of RASi and higher sodium levels are independently associated with higher Cl levels. 111134 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Effect of Prolonged Oral Pentoxifylline in Patients with Chronic Chagas' Cardiomyopathy: Results of a Prospective, Randomized, Double-Blind Pilot Study MARCUS VINICIUS SIMOES1, Karyta Suely Macedo Martins1, Antonio Carlos Barros-Filho1, Minna Moreira Dias Romano1, Denise Mayumi Tanaka1, Paulo Louzada-Junior1, Edecio Cunha-Neto2, Jose Antonio Marin-Neto1 (1) Faculdade de Medicina de Ribeirao Preto - USP, Ribeirao Preto, SP, Brasil; (2) Incor - Instituto do Coracao - FMUSP Background: The essential histopathologic lesion in chronic Chagas' cardiomyopathy (CCC) is a relentless low grade myocarditis with increased production of cytokines. Recent experimental studies have suggested that pentoxifylline, an immunomodulator that reduces the production of TNF-alfa, may be associated to a better evolution of CCC. Purpose: We tested the effect of pentoxifylline in cytokines profile and cardiac function in patients with CCC. Methods: This is a prospective double-blind clinical study, enrolling 38 CCC patients (age: 60 +/- 13 y.o., 66% male, LVEF = 48 +/- 7%), randomized to pentoxifylline (PTX, n = 19), 400 mg 3x/day for 6 months or placebo (PLC, n = 19). At baseline and post-treatment, patients underwent assessment of serum cytokines (IL6, IL10, TNF-alfa) and 2D-Echo with measurement of LVEF, indexed LV end diastolic volume (LVEDVi), LV wall motion score index (WMSi), tricuspid annulus systolic excursion (TAPSE). Mixed effects ANOVA for repeated measures was used to test the treatment effect between groups. Results: The table summarizes the results. We observed a strong trend toward reduction of TNF-alfa and increase of IL10 values in the PTX group, but no significant effect in cardiac function variables. Conclusion: Despite its immunomodulator effect, pentoxifylline was not associated to significant improvement in cardiac function in patients with CCC. 111145 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Indirect VO2 Analysis in Patients with Metabolic Syndrome JULIANA RIBEIRO GOUVEIA REIS1, Laissa de Cassia Alves2, Karine Siqueira Cabral Rocha2, Alessandro Reis3, Juliana Ribeiro Gouveia Reis1 (1) Instituto Pro-Vida; (2) Centro Universitario de Patos de Minas; (3) Hospital Santa Casa de Misericordia de Patos de Minas Metabolic syndrome is characterized by a set of cardiovascular risk factors such as arterial hypertension, insulin resistance, hyperinsulinemia, glucose intolerance/type 2 diabetes, central obesity and dyslipidemia. People with this condition have low functional capacity. The cardiopulmonary stress test is considered the gold standard in the assessment of physical capacity, however, it requires specific equipment and a specialized team. Therefore, the Shuttle walking test becomes a more practical option to estimate VO2 max in this population. The purpose of this study was evaluate the measurement of indirect VO2 in people with metabolic syndrome and compare it with predicted values for normality. This is a cross-sectional study with a quantitative approach. The inclusion criteria for the study were patients with metabolic syndrome who were being treated at the State Center for Specialized Care in Minas Gerais/Brazil, aged between 18 and 59 years. Patients with SatO2 < 88%, severe arterial hypertension, aortic coarctation, and decompensated heart failure were excluded. Patients underwent anthropometric assessment and then the Body Mass Index was calculated. The test was started after analyzing the contraindications and the VO2 obtained and the maximum expected VO2 were recorded. The results were analyzed using descriptive statistics, mean and standard deviation using the Wilcoxon test. The significance level was set at 0.05. The project received approval from the Research Ethics Committee under opinion number 3,153,984. Thirty patients participated in this research, 15 men and 15 women. The mean age of the male group was 55 years (+-3.6) and the mean age of the female group was 49 years (+-3.6). The mean BMI of the male group was 32.45 (+-3.44). The female group had a mean BMI of 33.77 (+-4.31). Regarding the VO2 of male patients, an average VO2 value of 12.84 (+-2.20) was observed, while the average VO2 maximum was 72.90 (+-2.12), with p value <0.05. In female patients, there was a lower value compared to males, with an average VO2 obtained of 12.52 (+-2.20), and VO2 max with an average of 36.31 (+-4.49), with a value of p < 0.05, also with mean values below the male participants. It is concluded that individuals with metabolic syndrome have low VO2 max values when compared to the expected values for this population and women have lower rates. 111149 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Nutritional Status and Prevalence of Breastfeeding in Preterm Infants with Congenital Heart Disease Pre-Surgery in Southern Brazil VIVIANE PAIVA DE CAMPOS1, Ana Carolina Krauspenhar Gluszczuk2, Nathalia Jacques Pereira2, Francisca Moura Strebel3, Fernanda Lucchese-Lobato4 (1) Instituto de Cardiologia/Fundacao Universitaria de Cardiologia Programa de Pos-graduacao em Ciencias da Saude: Cardiologia; (2) Universidade Federal do Rio Grande do Sul; (3) Universidade Federal de Ciencias da Saude de Porto Alegre; (4) Irmandade Santa Casa de Misericordia de Porto Alegre Background: About 320,000 preterm (PT) infants are born in Brazil annually. Of these, it is estimated that 10-15% have congenital heart disease (CHD). Infants with CHD are born with normal body weight and lose it substantially after birth. The stunted growth and low weight characteristic of CHD infants are associated with poor developmental and surgical outcomes. Due to the challenges that infants with CHD face they are less likely to breastfeed, which leaves them more vulnerable to a diminished immune system, incidence and severity of diseases, mortality, prolonged hospital stay, and developmental delays. Objective: To verify the prevalence of breastfeeding in PT infants with CHD admitted to a reference children's hospital in Southern Brazil between 2019-2022. Methods: This is a descriptive cross-sectional retrospective study. Data from medical records of PT infants (<37 weeks gestational age) with CHD, ages 0-12 months submitted to surgical procedures between 01/19 to 03/22, were analyzed. Infants with genetic syndromes were excluded from the analyses. Demographic, anthropometric, and clinical data were collected from electronic charts and entered into the REDCap data platform. Statistical analyses were performed using the SPSS v. 25 software. Results: The 62 infants included in the study were mainly late PT (34-36 weeks and 6 days; 68%), female (53%), white (73%), acyanotic CHD (58%), and SUS users (77%). Seventy percent of all infants had appropriate weight for gestational age at birth. Most infants were formula fed (73%), while only 27% received breast milk, either exclusively (3%), complemented with solids (5%), or mixed breast milk and formula (19%). Fifty-two percent used tube feeding exclusively. Only 13% of tube-fed infants received breast milk. At the time of surgery, 65% were severely stunted, 56% severely underweight and 50% extremely thin/thin in BMI. Conclusions: The findings suggest that premature infants with CHD in Southern Brazil are more likely to have an adequate nutritional profile at birth with increasing deficits and significant weight loss in the pre-surgical period. Due to the low prevalence of breastfeeding and high use of exclusive tube feeding, we conclude that it is of utmost importance to encourage breastfeeding and nutritional programs to promote weight gain and better immunity before surgery. Future multidisciplinary programs should focus on milk bank collection and inclusive breastfeeding pre-surgical protocols. 111197 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Feasibility and Safety of Prehospital Thrombolysis in Stemi by Paramedics using Motorbike Ambulance in India - Mission Delhi (Delhi Emergency Life Heart Attack Initiative): A Pilot Study RAMAKRISHNAN SIVASUBRAMANIAN1, Chandini Suvarna1, Praveen Aggarwal1, Sandeep Seth1, Neeraj Parekh1, Meenakshi Sharma2, Sheikh Vamik1, Ambuj Roy1, Ganesan Karthikeyan1, Sandeep Singh1, Rajiv Narang1, Balram Bhargava2 (1) All India Institute of Medical Sciences (AIIMS), New Delhi, India; (2) Indian Council of Medical Research (ICMR), New Delhi, India Background: Outcomes of ST elevation myocardial infarction (STEMI) are suboptimal in India. Pre-hospital thrombolysis is an established practice in developed countries for timely reperfusion in STEMI. Mission DELHI (Delhi Emergency Life Heart Attack Initiative) is a pilot project for pre-hospital thrombolysis using motorbike ambulance service by trained paramedics at the patient's doorstep in a selected geographical area of New Delhi. To the best of our knowledge, this is the first study of prehospital thrombolysis in India. Objective: In this pilot phase, we report the safety and feasibility of prehospital delivery of care in STEMI. Methods We covered a geographical area of 5-km around our institution. A command center was set up and the patients were required to call a dedicated helpline number. Upon initial screening, a motorcycle ambulance was dispatched to the caller's location. A brief history, physical examination and an ECG were obtained. ECG was electronically transmitted to the command center and thrombolysis with Tenecteplase was given at patient's doorstep after evaluation of the ECG by a cardiologist. Results: A total of 26 STEMI patients (mean age 56.2 years; 88.5% male) were treated either at home (46.2%), public places (23.1%), place of work (15.4%) or at small clinics (15.4%). Time taken to reach the patient location was 15.1 +- 6.1 min, and call to ECG time was 25.0 +- 6.8 min. Out of the 26 patients with STEMI, 15 patients were thrombolysed at a pre-hospital location with a door to needle time of 31 +- 11.1 min. Out of these, 13 patients had successful thrombolysis and had undergone further MI management. There was one death in a patient with cardiogenic shock. We also managed a total of 60 patients diagnosed with NSTEMI. Conclusions: In this pilot study, we have demonstrated the feasibility and safety of a telemedicine supported pre-hospital thrombolysis by paramedics at the patient's location. Such an approach is likely to significantly improve thrombolytic therapy usage and reduce ischemic times, and thereby could result in significant improvements in STEMI outcomes in a country like India. 111208 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Role of New Echocardiographic Modalities for Assessing Myocardial Evaluation of Fabry Disease Patients JOSE LUIZ BARROS PENA1, Isabel Cristina Gomes Moura1, Marcos Victor Prosdocimi Diniz1, Fabiano Maia Linhares1, Pedro Manuel Marques Cristovao1, Eduardo Back Sternick1, Amanda Marcos de Oliveira2, Gabriela de Campos Viveiros2, Rafaela Santos Garcia2, Eduardo Felipe Souza de Deus2, Tatiane Pires da Silva2, Tarcila Paoli Marques Moreira2 (1) Faculdade Ciencias Medicas de Minas Gerais; (2) Hospital Felicio Rocho Introduction: Due to its various clinical manifestations, Fabry disease (FD) is a commonly misdiagnosed rare condition. Treatment depends ideally on early disease detection and timely enzyme replacement therapy to improve prognosis. Echocardiography may be an efficient noninvasive technique to detect structural and functional heart consequences resulting from the disease. This study aimed to determine whether new echocardiographic modalities may contribute to more improved diagnoses. Material and methods: Prospective and transversal study of 15 patients (Pts) with FD. During one examination, conventional transthoracic, bi-, and tridimensional echocardiography as well as strain/strain rate speckle tracking were measured. Specific echocardiographic data were obtained and exported to a workstation for subsequent evaluation. Statistical analyses were performed with 5% significance using the R program, version 3.1.3. Results: Nine Pts (60%) were male, and the mean age was 39 +- 11.9 years. Pts presented increased left atrium volume index, mean left ventricle (LV) septum, and posterior wall thickness. LV hypertrophy was found in varying degrees in 8 (53%) FD Pts. Mean myocardial mass value measured by the 4D technique was 110.9 +- 8.1 grams. A binary appearance of LV endocardial border ("binary sign") and hypertrophy of the anterolateral papillary muscle were detected in 9 (60%) of Pts. Mitral regurgitation was present in 4 (26.7%) Pts, mitral valve prolapse in 2 (13.3%), and aortic regurgitation in 1 (6.7%). Four (26.7%) Pts presented RV hypertrophy. Global mean longitudinal 2D strain measured -19.5 +- 3.4%, and 4D circumferential strain measured -17.7 +- 3.5%. We identified peak systolic strain reduction in basal and mid inferolateral segments in 10 (66.6%) Pts. By analyzing the bull's-eye plot. Conclusion: Echocardiography is an accurate, robust tool in Fabry disease evaluation. Compared to conventional measurement techniques, advances in 3D and speckle tracking echocardiography have augmented and improved anatomical and functional data. 111251 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Role of Check Up in the Prevention of Cardiovascular Diseases FERNANDA SANCHES AGUERA GROCHOCKI1, LAIS SANCHES AGUERA1, CRISTINA PELLEGRINO BAENA1, JOSE ROCHA FARIA NETO1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DO PARANA - PUCPR Introduction: Cardiovascular diseases are the leading cause of mortality in the world. The identification and correction of modifiable risk factors are the cornerstone of cardiovascular prevention. However, this purpose in performing periodic health assessment (check-up) in asymptomatic individuals still has its effectiveness questioned. Objective: To analyze whether the periodic health assessment can be a tool for the control and treatment of cardiometabolic risk factors and whether the impact of this assessment is different according to the presence of these factors. Methods: A retrospective cohort was carried out, including data from patients seen consecutively in 2015 and 2016, at a check-up service in Curitiba, Parana. The cardiometabolic profile of the patients was evaluated and a comparison was made between variables of interest obtained in 2015 and 2016. It was also evaluated whether the variation from one year to the other was different between patients who presented cardiometabolic alterations in the first year compared to those who presented variables without alterations. Microsoft Excel and SPSS Statistics programs were used for calculations, using Student's T test for paired samples or Wilcoxon test, according to normality tests. Results: A total of 478 patients were included, 80.3% of whom were male and with a mean age of 46.29 years (SD +- 8.06). The following altered variables showed improvement: triglycerides (p < 0.05), HDL (p < 0.001), LDL (p < 0.001), non-HDL (p < 0.001), fasting glucose (p < 0.001) and glycated hemoglobin (p < 0.001). Evaluating altered anthropometric data, there was an improvement in Body Mass Index(BMI) (p < 0.01), Systolic Blood Pressure (p < 0.001), Diastolic Blood Pressure (p < 0.001) and male waist circumference (p < 0.05). Analyzing the altered variables, there was a change to values within the normal range in 21% of cases of total cholesterol, 29% triglycerides, 26% HDL, 27% LDL, 32% non-HDL, 7% BMI, 87% systolic blood pressure, 84% Diastolic blood pressure, 10% waist circumference, 54% blood glucose, 43% glycated hemoglobin. (p < 0.001). Conclusion: Periodic health assessment seems to have a positive impact on the control and treatment of cardiovascular risk factors. This effect was mainly observed in patients who already had altered laboratory and anthropometric variables in the first evaluation. 111254 Modality: E-Poster Researcher - Non-case Report Category: CARDIO-ONCOLOGY Myocardial Strain by Speckle-Tracking and Evaluation of 3D Ejection Fraction in Drug-Induced Cardiotoxicity's Approach in Breast Cancer DANIANE RAFAEL1, Juliana Bueno Refundini1, Adriana A. da Silva1, Ana Cristina Camarozano1, Claudio Leinig Pereira da Cunha1, Sergio Lunardon Padilha1, Admar Moraes de Souza1, Ana Karyn Ehrenfried de Freitas1 (1) Universidade Federal do Parana - UFPR Chemotherapeutics brought greater survival to breast cancer patients, however, they can generate cardiotoxicity with important dysfunction. The echocardiogram (Echo), has enabled early detection of myocardial dysfunction. Our purposes was to obtain, with Echo, the incidence of left ventricle dysfunction after chemotherapy, analyzing the Ejection Fraction (EF) in 2 dimensions-Simpson Method (2D) and in 3 dimensions (3D), and to identify early contractile changes using the Longitudinal Strain - Speckle-Tracking (ST). A prospective study studied 37 women, mean age 48 +- 11 years with breast cancer in the beginning of chemotherapy between 2013 and 2015. Echo was performed at baseline, after 3 and 6 months, evaluating 2D EF and 3D EF in addition to the contractile evaluation using the ST and peak systolic velocity at the base of the lateral wall (lateral S') on tissue Doppler. The patients were also evaluated for signs, symptoms, possible risk and protective factors contributing to myocardial dysfunction overall. Dyspnea was the only symptom detected (23%). We observed that the altered ST in the 1st exam proved to be a predictor of 3D EF reduction in the 3rd exam (p = 0.049). The lateral S' reduced at 6 months, corroborating the change in systolic function. Both risk and protective factors did not affect the parameters evaluated. There was a progressive decrease in EF after exposure to cardiotoxic chemotherapeutic agents, which became more evident by 3D analysis. The evaluation of the ST showed significant changes associated with the period of administration of anthracycline, and an ST altered in the beginning of the treatment was a predictor of EF reduction at 6 months of treatment. These findings support the importance of these new Echo techniques in the follow up of these patients. 111263 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Prevalence of Silent Brain Infarct in Mitral Stenosis and its Predictors AMBUJ ROY1, Ambuj Roy1, Nitish Naik1, Sharma Sanjiv1, Sandeep Singh1, Gautam Sharma1, Ramakrishnan Lakshmy1, Rohit Bhatia1 (1) All India Institute of Medical Sciences (AIIMS) Background: Rheumatic mitral stenosis (MS) is associated with significant morbidity, especially ischemic stroke(IS) and continues to be very prevalent in developing countries. Clinical predictors of IS are poor and is common even among those not in atrial fibrillation (AF). Silent brain infarct (SBI) is an important predictor and surrogate of future ischemic stroke. In this study, we assessed the prevalence of SBI in patients with MS in normal sinus rhythm (NSR) and AF. Methods: Consecutive patients with more than moderate mitral stenosis underwent non-contrast MRI. Standard MRI sequences and definitions for infarct were used. Patients with prior intervention and surgery for MS were excluded as were those with prior clinical IS or transient ischemic attack (TIA), left atrial clot, and severe concomitant other valval lesions. Results: Of 211 patients who underwent MRI, 140 were in NSR and 71 in AF. 59% were females, 88% had severe MS, 23%, 24% and 53% were in NYHA Class I, II and III respectively. A total of 44 (21%) patients had SBI. The baseline variables in those with normal MRI scans and with SBI were as in Table 1. Only NYHA functional class and not AF was significantly different in patients with SBI. Conclusions: SBI is common among patients with MS including those in NSR. Only NYHA class was different in the two groups. Better predictors of IS beyond rhythm are needed in patients with MS to decide on IS preventive strategies. 111280 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Preoperative Physical Status and In-Hospital Outcomes After Cardiac Surgery ABISAI DOS SANTOS SANTANA1, Giovana Corte Real Ruffier2, Mauro Felippe Felix Mediano1, Daniel Arthur Barata Kasal1 (1) Instituto Nacional de Cardiologia; (2) Universidade do Estado do Rio de Janeiro Introduction: The assessment of physical performance in the preoperative evaluation of open-chest heart surgery (OHS) can help to establish the most appropriate moment for the intervention. There are noninvasive and simple methods that can be used at the bedside, in order to evaluate physical performance in these patients. Objective: To evaluate physical performance in the preoperatory period of elective OHS and establish associations with surgical recovery outcomes. Methods: Adult patients subjected to elective OHS, either coronary artery bypass grafting (CABG) or valvular replacement (VR) surgery, at a quaternary hospital were recruited for the study. Physical performance was measured with 30-s chair-stand-test (30sCST), timed up and go test (TUGT) and hand grip, performed during surgical admission, before the intervention. Surgical risk was estimated with the Euroscore II risk score. Clinical data were obtained using medical records. The outcomes evaluated were mechanical ventilation time (MVT), admission time (AT), and in-hospital death (IHD), and their associations with the physical tests were evaluated with either logistic (IHD) or linear (MVT, AT) regressions (p < 0.05). Results: One hundred sixty-six individuals were evaluated, most patients were male (65%), aged 58.3 +- 11.3 years, and with body mass index of 27 +- 4.4 kg/m2. Left ventricular ejection fraction (Teicholz) was 59.4 +- 15.5%, and New York Heart Association functional classes I, II, III and IV were 8, 70, 53, and 3%, respectively. Euroscore II was 3.1 +- 2.1, 98% of surgeries employed extracorporeal circulation, and IHD was 7.2%. In the unadjusted analysis, the hand grip was associated with IHD (OR 0.90; p = 0.007), but the association was not significant after adjustments for age and sex, or Euroscore II (OR 1.00 p = 0.93 and OR 0.92 p = 0.06, respectively). None of the physical tests were associated with either AT or VMT. Conclusions: The present results suggest a lack of association between the 30sCST and TUGT physical tests and the recovery variables after OHS studied. Preoperatory hand grip offered an association with mortality after surgery, but significance was borderline after adjustment for Euroscore II. The contribution of physical fitness before OHS to surgery outcomes may be evaluated with additional methods and in particular groups such as the elderly in future studies, in order to explore this important association. 111769 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Analysis of the Impact of Implantable Cardioverter-Defibrillator Therapy in Patients with Hypertrophic Cardiomyopathy LUCAS CARVALHO DIAS1, Luiz Eduardo Montengro Camanho2, Eduardo Benchimol Saad2, Charles Slater1, Luiz Antonio Oliveira Inacio Junior2, Gustavo Vignoli Santos2, Ricardo Mourilhe Rocha1 (1) Hospital Universitario Pedro Ernesto; (2) Hospital Pro-Cardiaco Introduction: The hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease, strongly related to the occurrence of malignant ventricular arrhythmias and sudden death. Objective: Describe the clinical data and the occurrence of appropriate and inappropriate therapy in a subgroup of HCM patients with implantable cardioverter-defibrillators. Methods and results: In a cohort of 720 consecutive and retrospective patients, monitored from March 2006 to December 2021, with 57 of this total being diagnosed with HCM. The male sex was found in 42 (74%), and the average age was 54.6 years. ICD implantation by primary prophylaxis occurred in 49 (86%) patients and in 8 (14%) by secondary prophylaxis. The report of unexplained syncope was observed in 50 (88%) patients. At the time of ICD implantation, the records showed that 51 (89%) patients were in NYHA functional class 1 and the average LVEF was 59,4%. The electrocardiographic analysis showed that the mean QRS was 118 ms and that 25 (44%) had an LBBB pattern. During the ICD monitoring period, 11 patients (19%) were observed with a record of VF/VT and appropriate therapy. Inappropriate therapy was observed in 7 patients (12%), all in the AF group, which occurred in 25 (44%) patients throughout the record. Conclusion: Despite the not insignificant number of inappropriate therapies, the ICD has been shown to be an effective therapy in preventing sudden cardiac death and in the clinical management. 111563 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Digital Therapeutic as a Tool to Manage Cardiovascular Risk Factors: Preliminary Results of a Brazilian Cohort CAMILA MACIEL DE OLIVEIRA1, Roberto Luis Zagury3, Luiza Borcony Bolognese4, Davi Casale Aragon5, Livia Mandina da Graca Couto2, Marcela Carvalho2, Thaiza dos Anjos2, Mercedes Balcells6, Clemente Nobrega2, Chunyu Liu7 (1) Universidade Federal do Parana (UFPR); (2) Klivo LLC; (3) Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE); (4) Pontificia Universidade Catolica de Minas Gerais (PUC-Pocos); (5) Universidade de Sao Paulo (USP-RP); (6) Massachusetts Institute of Technology; (7) Boston University Digital therapeutics, an emerging type of medical approach, is defined as evidence-based interventions through qualified software programs that help prevent, manage, or treat chronic diseases. We aim to describe the clinical impact of a digital therapeutic product of a Brazilian startup company that focuses on individual needs as an essential shift for the ongoing management of patients with chronic conditions such as diabetes, hypertension, and dyslipidemia. This program is a model of behavior change based on an intensive lifestyle intervention method and seeks to manage cardiovascular risk factors in adults aged >= 18 years. It was sponsored by health plans and healthcare provider organizations and was free for patients. During the management process, patients were remotely supervised by nurses on a weekly basis via phone calls intended at health education and assessment of laboratorial outcomes. An app was developed to improve the communication between patients and nurses, but e-mails and text messages were also used. To improve control of glycemic events in patients with diabetes, a glucometer was sent to the patient's home and was connected to the app. When abnormal glucose parameters were detected, the patient was contacted according to an established protocol. Outcomes of interest were evaluated at baseline and after 3 months. For a total of 2544 patients (53.35 +- 13.45 years; 50% male) distributed in 21 Brazilian states (40% in Sao Paulo), it was possible to verify significantly improved glycemic and lipid profile (total cholesterol and LDL-cholesterol) after follow-up for 3 months. A1c decreased (9.13 +- 2.10 versus 7.14 +- 1.69; p < 0.01), and so did fasting glucose (127.19 +- 51.96 versus 122.51 +- 42.40; p = 0.03), total cholesterol (176.66 +- 50.11 versus 161.36 +- 45.72; p = 0.01), and LDL-cholesterol (100.42 +- 40.11 versus 89.87 +- 33.82; p = 0.03). No difference was observed for HDL-cholesterol or triglycerides in this sample. This program has shown promising findings related to glycemic and lipid profiles, providing insights into the management of cardiovascular risk factors, which will allow us to reshape this unique therapeutic approach for the Brazilian population continuously. 111319 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Characteristics and Clinical Outcomes of Patients with Heart Failure with Preserved Ejection Fraction: Insights from the First Brazilian Registry of Heart Failure (Breathe) PEDRO GABRIEL MELO DE BARROS E SILVA1, Denilson Campos Albuquerque3, Marcus Vinicius Simoes5, Renato Delascio Lopes6, Conrado Hoffmann7, Paulo Roberto Nogueira8, Helder Reis9, Fabio Akio Nishijuka10, Lidia Zyntynski Moura11, Fernando Bacal3, Evandro Tinoco Mesquita3, Mucio Tavares de Oliveira Junior3 (1) IP-Hcor; (2) Hospital Samaritano Paulista; (3) Sociedade Brasileira de Cardiologia; (4) Hospital Copa D'Or; (5) Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo; (6) Brazilian Clinical Research Institute; (7) Hospital Regional Hans Dieter Schmidt; (8) Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto; (9) Hospital de Clinicas Gaspar Viana; (10) Hospital Naval Marcilio Dias; (11) Irmandade Santa Casa de Misericordia de Curitiba; (12) Instituto do Coracao (INCOR HC FMUSP) Background: Heart failure with preserved ejection fraction (HFpEF) accounts for almost half of the HF cases. However, little is known about the characteristics, medical therapies, and long-term prognosis of patients hospitalized with HFpEF in Latin America. Methods: BREATHE was a nation-wide prospective registry that included patients hospitalized due to acute heart failure (AHF) in Brazil. In-hospital management as well as 12-month clinical outcomes were assessed. In the current analysis, patients were classified according to left ventricular ejection fraction (LVEF) in 3 groups: <40% (HFrEF), 40 to 49% (HFmrEF) and >=50% (HFpEF). Results: A total of 3,013 patients were included with a median follow-up of 346 days. In 1,204 patients, the LVEF was assessed during the first 24 hours of hospitalization with 28.1% of patients classified as HFpEF. The patients with HFpEF were older (70.5 +- 16.4 vs 63 +- 15.9; P < 0.01) had more female patients than HFrEF ones (57.5% vs 30.4%; P < 0.01). Among comorbidities, hypertension (81.4% vs 70.5%) and atrial fibrillation (40.5% vs 27.2%) were more common in patients with HFpEF (both P < 0.01), while history of myocardial infarction was more common in HFrEF (18.9% vs 29.4%; P < 0.01). The creatinine was 1.5 +- 1.0 mg/dL and similar among the 3 groups but the level of BNP/NT-ProBNP was >2 times lower in the HFpEF population. The wet-cold profile occurred in 5.9% of the patients with HFpEF and in 12.6% of patients admitted with HFrEF (P = 0.04). The main cause of decompensation was poor adherence in the HFrEF patients, and infection in HFpEF. At hospital admission, almost 54% of HFpEF patients were using renin-angiotensin-aldosterone inhibitors or beta-blockers, and 19.5% were using spironolactone. There was no enhancement in the use of these medications during the 12 months follow-up. Intra-hospital mortality was similar among the 3 groups of LVEF (average 10.5%). After discharge, the mortality and hospital readmission rates at 365 days were not statistically different in all groups (23.3 deaths for 100 patient years with 51% readmission rate at 12 months in the HFpEF group). Conclusions: In this large multicentre nationwide Brazilian prospective registry of AHF, patients with HFpEF presented different clinical characteristics but similar prognosis compared to patients with lower ejection fraction during one year of follow-up. Improvement in the medical care is necessary to minimize complications in this high-risk population. 111345 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Spatial-Temporal Deep Learning for Automatic Detection of Echocardiographic Predictors of Mortality in Patients Hospitalized with COVID-19 BRUNO RAMOS NASCIMENTO1, Washington Luis S. Ramos2, Gisele Lobo Pappa2, Edson Roteia Araujo Junior2, Joao Francisco Barreto da Silva Martins2, Wagner Meira Junior2, Sander Luis Gomes Pimentel1, Juliane Franco1, Kaciane Krauss Bruno Oliveira1, Maria Carmo Pereira Nunes1, Antonio Luiz Pinho Ribeiro1, Erickson Rangel do Nascimento2 (1) Servico de Cardiologia e Cirurgia Cardiovascular e Centro de Telessaude do Hospital das Clinicas da UFMG, Belo Horizonte - MG, Brazil; (2) Departamento de Ciencia da Computacao da Universidade Federal de Minas Gerais, Belo Horizonte - MG, Brazil Introduction: Cardiac involvement seems to impact prognosis of COVID-19. Bedside echocardiography (echo) holds promise for early prediction of unfavorable outcomes, and artificial intelligence may be an additional tool to overcome personnel limitations. We propose a spatial-temporal deep learning-based approach for automatic prediction of mortality of inpatients with COVID-19 with echo images. Methods: Patients admitted in 2 reference hospitals in Brazil in 90 days with confirmed moderate and severe COVID-19, based on the Berlin criteria, underwent clinical and laboratory evaluation, and focused bedside echo (GE Vivid IQ), following admission, with remote interpretation by telemedicine in Brazil and the US. Independent echo predictors of all-cause mortality were assessed, after adjustment for clinical variables. Our image dataset consists of 737 videos (Mpeg) collected from included patients in 3 different probe positions: apical 4-chamber and parasternal long and short axis. It was used to predict the patients' outcome (discharge or death) in a 10-fold cross-validation procedure manner. We used a 2-stream deep neural network composed of two identical ResNet-18 Convolutional Neural Networks (CNN) - originally developed for Rheumatic Heart Disease diagnosis - followed by attention units to extract relevant spatial and temporal features from RGB and Optical Flow frames. A final softmax layer is used for classification, and accuracy measures are presented with 95% confidence intervals (CI). Results: Total 163 patients were enrolled, mean age was 64 +- 16 years, 107 (66%) were admitted to intensive care and in-hospital mortality was 34% (N = 56). Independent predictors of mortality, after adjustment for clinical and demographic variables, were age >= 63 years (OR = 5.53, 95%CI 1.52-20.17), LVEF < 64% (OR = 7.37, 95%CI 2.10-25.94) and TAPSE < 18.5 mm (OR = 9.43, 95% CI 2.57-35.03), C-statistic = 0.83. During training, we rescaled videos to 224 x 224 pixels and used temporal jittering to select a final clip with 32 frames per video in random batches of size 6. Our proposed method achieved an exam-wise accuracy of 61.21% (95%CI 50.87-71,55), sensitivity of 59.31% (95%CI 36.12-82.5) and specificity of 65.18% (95%CI 45.08-85.28) for mortality. Conclusion: Automatic detection of high-risk echo findings in COVID-19 inpatients at bedside seems feasible and, with more research, can improve mortality prediction at the point-of-care, especially in low-income settings. 111379 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Urban Chagas Disease: Identification of High Risk Patients EZEQUIEL J ZAIDEL1, Lara Gheco1, Luis Guillermo Garcia Chamorro1, Erna Florencia Segovia1, Diego Carvallo Claros1, Elena Vargas Parra1, Agustin Monzon1, Brian Perotti1, Maria Ines Sosa Liprandi1, Alvaro Sosa Liprandi1 (1) Sanatorio Guemes, Buenos Aires, Argentina Introduction: Migratory movements have led to Chagas disease (CD) being diagnosed in non-endemic areas. There are few epidemiological studies on the prevalence and behavior of the disease in urban areas. Aim: To describe the clinical profile of patients with CD evaluated in an urban area and to identify the frequency of high risk cases. Methods: Retrospective cohort study of patients who were hospitalized or evaluated in outpatient clinics, in a third level center from Buenos Aires. Patients over 18 years of age with a diagnosis confirmed by serology were selected. The patients were evaluated by clinical examination and complementary studies in accordance with current standards. A descriptive analysis was performed and the risk scores of Viotti, Rassi, Pinho Ribeiro, and Sousa were analyzed. Results: Data from 46 patients were analyzed, with a mean age of 61 +- 11 years, and 41% female. Main origin of patiets was nothern provincies from Argentina, as well as Bolivia and Paraguay. The diagnosis was made mainly by medical check-up due to risk factors for ECH (30%) or by finding in blood banks (10.8%). The median time of evolution from the date of diagnosis of the disease to the cutoff made for this analysis was 6 years (IQR 1-12). Only one case in this cohort had received trypanocidal treatment. The prevalence of cardiomegaly was 51% by radiography, but the diastolic diameter by echocardiogram was 51 mm +- 7 mm with a mean ejection fraction of 58%. 21% presented right bundle branch block, 4% left anterior hemiblock, 18% atrial fibrillation, and 6% low voltage and ventricular extrasystoles. Fifty percent had symptomatic heart failure, 23% had implanted cardiac devices, and 17% had cerebrovascular accident (CVA). No cases of digestive or neurological pathology were found. By Viotti score, 41% had a high risk of progression. Using Rassi score, 10% had a high risk of mortality, but by the Pinho Ribeiro score, only 1 patient had a high risk. When analyzing the risk of stroke, 16% of the cohort presented high risk by Sousa score, however, anticoagulation in this cohort was prescribed only to subjects with atrial fibrillation or those who had already had a stroke. Conclusions: The evaluation of patients with urban CD is a growing challenge for cardiologists from urban settings: Using current scores, the proportion of high risk cases was variabe, highlighting the need of better stratification tools. 111386 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Syncope and Pre-Syncope: Predictor of Unfavorable Outcomes in the Electrophysiological Study in Chronic Chagas Heart Disease IEDA PRATA COSTA1, Eduardo Arrais Rocha1, Almino Cavalcante Rocha Neto1, Roberto Lima Farias1, Daniele Melo Leopoldino1, Cristiane Liberato1, Ronaldo Vacsoncelos Tavora2 (1) Hospital Universitario Walter Cantidio - universidade Federal Ceara; (2) Hospital de Messejana _ SESA/CE Introduction: Cardiovascular death is the main cause of death in chronic Chagas' heart disease (CCC). Syncope in CCC can be caused by bradyarrthymias (sick sinus syndrome-SSS and conduction disorders) or ventricular arrhythmias. Objectives: To evaluate the association of syncope and pre-syncope with important unfavorable outcomes (SSS, severe conduction system disorders - HV >70 ms and VT/VF) in the electrophysiological study (EPS) in patients with CCC. Methods: This is a prospective cohort study, including 52 patients with CCC from the postgraduate's research project, 48 of whom underwent an EPS with or without previous use of antiarrhythmic drugs; with a mean age of 57 + 10.2 years; 62.5% male. PTs were classified into two groups: syncope/pre-syncope and syncope. The chi-square test and Fisher's exact test were used for statistical analysis. Results: The clinical characteristics were the mean: Rassi score was 8.43 + 4.8 points (39.5% low risk); 43.7% used antiarrhythmics; 8.3% had Functional Class III/IV and 79.1% (38pt) had syncope/pre-syncope. In group I, we observed that 31.2% (10pt) were at low risk of Rassi and 71.8% (23pt) had altered EPS (1 by SSS, 1 by prolonged HV and 21 by VT). In group II, we found 56.2% (9pt) low risk and 25% (4pt) had altered EPS. Unfavorable outcomes in the EEF were greater in group I than in group II (p = 0.002). Comparing the risk of Rassi and the presence of altered EPS, in the groups we have: Group %, .4% and % altered EPS (p = 0.83). Group II - Low risk - 11%, Intermediate 42.8% altered EPS(p = 0.57). Conclusions: Syncope/pre-syncope was a predictor of unfavorable outcomes in the EPS. The presence of altered EPS was similar in the different Rassi risk scores in both groups. 111401 Modality: E-Poster Researcher - Non-case Report Category: NURSING Teaching Strategy on Electrocardiogram in Undergraduate Nursing ERICA SOBRAL GONDIM1, Antonia Elizangela Alves Moreira1, Ana Camila Goncalves Leonel1, Amanda da Costa Sousa1, Emiliana Bezerra Gomes1 (1) Universidade Regional do Cariri - URCA Introduction: The electrocardiogram (ECG) subsidizes an assertive nursing care plan aimed at cardiac conduction abnormalities. But there are difficulties in performing and interpreting the test, which demonstrates the need for teaching strategies for its understanding and skills development. Objective: To report a teaching strategy on ECG shared between a professor, a student in teaching internship and an undergraduate teaching assistant. Method: Experience report of theoretical and practical teaching about ECG, carried out in October 2021 with 36 undergraduate nursing students, in a public university in Northeast, completed in two phases: theoretical, (skills training) and practical (simulation and case studies). Results: The implementation of the strategy used theoretical-practical association in a transversal way, which stimulated the development of knowledge, skills and attitudes, emphasizing the creativity and improvisation demonstrated due to the scarcity of materials at the public university. Finally, the promoters of the teaching strategy shared the potentialities and difficulties perceived in the process. The main potentiality was the motivation demonstrated by the students as a result of the interactivity and dynamics of the class, which stimulated their interest and active participation in both moments of the strategy. The biggest obstacle was the scarcity of resources, making it necessary to use low-fidelity simulation to replace the equipment and electrodes themselves. The heterogeneity of the learning process was also mentioned as a difficulty, since there are different ways to build knowledge aimed at different audiences, but it was evident from the students' reports that the strategy guided the necessary aspects of the teaching theme. Conclusion: Reporting the experience of teaching with simulation allowed the promoters to improve their strategies based on the students' feedback and the development of the activity. We suggest studies that enable the development of skills with the use of dynamic and participatory strategies. 111415 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Ultra-Minimalistic TAVR During COVID-19 Pandemic SEBASTIAN DARIO PERALTA1, Marcelo Omar Bettinotti1, Carlos Maximiliano Giuliani1, Guillermo Jubany1, Luis Murillo1, Juan Grieve Bruno1, Ezequiel Jose Zaidel1, Luis Carlos Sztejfman2, Matias Sztejfman2 (1) Sanatorio Guemes, Buenos Aires, Argentina; (2) Sanatorio Finochietto, Buenos Aires, Argentina Introduction: Current transcatheter aortic valve replacement (TAVR) procedures may be performed with an ultra-minimalistic approach which improves hospital resources. Aims The aim was to describe in hospital length of stay (LOS) and vascular events of TAVR procedures using ultra minimalisitc approach prior and during the COVID-19 pandemic. Methods: Consecutive TAVR cases from two centres between Jan 2019 and June 2021 were analyzed. Ultra-minimalistic approach included: all in one (AIO) femoral single puncture, conscious sedation, self-expanding valves, and femoral closure devices. Intra-pandemic cases were considered since March 2020 according to country's COVID 19 uptake. Conventional descriptive and comparative statisitics were performed with Epi Info V7. Results: 37 cases were included, 21 (56%) before the pandemic and 16 intra-pandemic. Mean age was 82 (6) years and 59% were female. 73% had no prior conduction abnormalities, 35% had concomitant peripheral artery disease, 8% porcelain aorta. Median EuroScore was 5.8 (IQR 4.2-8), STS 5.4 (IQR 3.6-7.2), mean ejection fraction 56% (SD 11%) and mean gradient at baseline 45 mmHg (SD 12). A self-expandable valve was used in all cases. A predilatation was used for all cases. There were no deaths, no bleeding events, no strokes nor infections, 1 case of vascular complication (iliac dissection, resolved during the same procedure) and 1 case of permanent pacemaker implantation (2.7%). The rate of mild paravalvular leak was 43% and moderate leak 5.4%. Median length of stay was 2 days (IQR 2-3). 16 cases (43%) were performed intra-pandemic, without differences in procedural duration (58 minutes vs 56 pre-pandemic, p = 0.56), nor in LOS (median = 2 days in both groups, p = 0.24). 16% of the cases were discharged at day 1. Conclusion: Ultra-minimalisitc TAVR was safe and associated with short LOS prior and during COVID-19 pandemic. Physicians and patients must consider these findings in the context of the pandemic with risk of in-hospital infections and low healthcare capacity. These results must be considered also for TAVR cost-effectiveness analysis. 112184 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Myocardial Perfusion and Fractional Flow Reserve by Computed Tomography and Scintigraphy in Patients with Ischemia by Exercise Stress Test SERGIO RODRIGO BERALDO1, Sergio Rodrigo Beraldo1, Tiago Augusto Magalhaes1, Augusto Hiroshi Uchida2, Rafael Willain Lopes3, Douglas Carli Silva4, Erico Luiz Camacho5, Gabriel Nunes Rodrigues5, Paulo Roberto Maia6, Ana Clara Beraldo Muniz6, Carlos Eduardo Rochitte1 (1) Computed Tomography and Cardiovascular Magnetic Resonance Sector from Heart Institute (InCor), University of Sao Paulo Medical School.; (2) Hospital Israelita Albert Einstein; (3) Nuclear Medicine Sector of Hospital do Coracao -HCOR; (4) Siemens Healthineers; (5) Corpus Computed Tomography and Magsul MND Nuclear Medicine; (6) Sapucai Valley University School of Medicine Background: Patients with low to intermediate probability of CAD presenting exercise treadmill test (ETT) consistent with myocardial ischemia is a common scenario and may lead to other complementary tests, frequently myocardial scintigraphy (SPECT). Purpose: We sought to evaluate the diagnostic performance of myocardial perfusion (CTP), and Fractional Flow Reserve Derived from Computed Tomography - (cFFR) compared to SPECT in a population of patients with inducible ischemia on exercise treadmill tests (ET), using coronary computed tomography angiography (CTA) as the reference method. Methods: Sixty patients (58.4 +- 9.2, 37 men (61.7%), underwent clinical evaluation and two non-invasive imaging exams: SPECT and CTA with CTP during stress with dipyridamole. Results: SPECT showed significantly lower diagnostic accuracy than CTP (AUC 0.62 vs. 0.72, p < 0.001). The cFFR and minimal luminal area showed higher diagnostic accuracy than perfusional methods (AUC = 0.86 and 0.90). Coronary calcium score (CAC) showed AUC of 0.72 for the detection of obstructive CAD by CTA. In a per-patient analysis, CAC score and CTA were the strongest predictor of revascularization (AUC 0.87 and 0.94 p < 0,001). Conclusions: CTP alone presented higher accuracy than SPECT in patients with positive ETT with low or intermediate probability of CAD. Adding the cFFR and CAC data increases the diagnostic accuracy by computed tomography. These results suggest the use of CTP, cFFR or CAC in clinical practice might be adequate alternatives to SPECT in this scenario. 111437 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Determinants of Vasoplegic Syndrome After Cardiac Surgery in Patients not using Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker GABRIEL ASSIS LOPES DO CARMO1, Barbara Carolina Silva Almeida1, Gabriela Zamunaro Lopes Ruiz1, Renato Braulio1, Ana Cristina Carioca1, Fabio Morato Castilho1, Claudio Leo Gelape1, Bruno Rodrigues Pereira1, Luiza Moreira Gomes1, Ana Carolina Sudario Leite1 (1) Universidade Federal de Minas Gerais (UFMG) Introduction: Vasoplegia after cardiac surgery is a well described complication, closely related to increased mortality. It is associated with use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Therefore, we routinely discontinue these medications before elective surgeries. However, we still face several cases of vasoplegia. Objective: Describe clinical characteristics associated with vasoplegic syndrome after elective cardiac surgery. Methodology: Prospective cohort analysis of cardiac surgery patients in a public hospital in Brazil between 2016 and 2021, excluding heart transplant. Results: We enrolled 406 patients, median age 57 (46;66) and 214 (52,7%) females. 287 (70,7%) had valve surgery, 99 (24,4%) coronary artery bypass graft, 29 (7,1%) congenital heart correction, 17 (4,2) aorta procedures and 33 (8,1%) other cardiac surgeries. Univariate analysis showed that age, 64 (57;73) vs 55 (44;65), p < 0,001, chronic obstructive pulmonary disease, 47,1% vs 16,5%, OR = 4,51 (1,68-12,15), p0,004, renal replacement therapy (RRT), 57,1% vs 17%, OR = 6,49 (1,42-29,66), p = 0,021, and aortic surgery, 41,2% vs 16,7%, OR = 3,49 (1,28-9,50), p = 0,018, were associated with vasoplegia. After multivariate analysis, age, OR = 1,068 (1,041-1,095), p = 0,005, RRT, OR = 5,77 (1,12-29,69), p < 0,001, and aorta procedures, OR = 3,45 (1,17-10,17), p = 0,025, remained statistically significant. Conclusion: Our study shows that older age, RRT and aortic procedures are associated with higher incidence of vasoplegia in elective cardiac surgeries. All these factors are non-modifiable, but could add some information in the decision to perform a surgery in selected patients, as well as planning best intra and post operative monitorization strategies. Therefore, the diagnosis of vasoplegia could be made as soon as possible and appropriate therapy could be started earlier. 111439 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Contribution of the Vectorcardiogram in the Differential Diagnosis of Brugada Electrocardiographic Pattern BRUNA AFFONSO MADALOSO1, Nelson Samesima1, Nancy Maria Martins de Oliveira Tobias1, Caio de Assis Moura Tavares1, Horacio Gomes Pereira Filho1, Mirella Espanhoto Facin1, Carlos Alberto Pastore1 (1) Clinical Unit of Electrocardiography - Instituto do Coracao (INCOR), Hospital das Clinicas FMUSP Background: The electrocardiogram (ECG) is a powerful tool for differential diagnosis among a group of pathologies called J-wave syndrome. The vectorcardiogram (VCG) can be used as a complementary method to the ECG in several dubious alterations. Purpose: We carried out a VCG analysis; after conceiving a novel parameter (JT-distance), that quantified the visual VCG change observed, in most Brugada type-1 patients and that allows diagnosis of the Brugada ECG pattern. Methods: We selected ninety-six ECGs (test cohort) with J-point elevation in V1/V2, ECG superior leads and VCGs, all performed on the same day. The VCG measurement by Frank method (JT-distance) was designed in transverse and right sagittal planes by three lines drawn 1) at the final third of the QRS loop, comprehending J-point; 2) at the initial portion of the T loop; 3) a parallel of the J-point line at the beginning of T loop. JT measure was determined by the distance between parallels. A validation cohort of thirty-five patients was also established. Results: JT-distance >=1.5 mm (transverse plane) and JT-distance >1.25 mm (right sagittal plane), differentiated Brugada type-1 from type-2, early repolarization and others, with 95% sensitivity,68% specificity (p < 0.05). JT-distance <1.5 mm (transverse plane) and JT >1.25 mm (right sagittal plane) had 100% sensitivity, 85% specificity (p < 0.05) for Brugada type-1 diagnosis . Validation cohort showed JT distance >=1.5 mm (transverse plane) could differentiate both Brugada types from others with sensitivity of 61%, specificity of 94%, (p = 0.0009). When JT distance (transverse plane) was <1.5 mm and in right sagittal plane was >1.25 mm, we found sensitivity of 83%,specificity of 94%, for Brugada type-1 diagnosis. (p = 0.001). Both cohorts showed very similar Cohen's kappa levels (0.65 vs 0.77, test and validation cohorts, respectively). Conclusions: The novel vectorcardiogram measurement (JT-distance) presented a new diagnostic criterion to identify Brugada pattern with a practical and possible reproducible method. Nevertheless, prospective studies should also be performed to confirm these findings. 111440 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Low Adiponectin as a Risk Factor in Cardiovascular Diseases (CVD) in Obesity ARCHNA SINGH1, Sakshi Shukla1, Sandeep Aggarwal1 (1) All India Institute of Medical Sciences, New Delhi Aim: Adiponectin is a cytokine produced by adipocytes that act on specific receptors of several tissues through autocrine, paracrine, and endocrine signaling mechanisms. Adiponectin circulates in different oligomeric isoforms, with different biological effects. Circulating levels of adiponectin decline under conditions of metabolic stress, including obesity and metabolic syndrome, and are associated with decreased adiponectin signaling. Adiponectin has insulin-sensitizing effects and antiatherogenic properties. Higher adiponectin has been associated with decreased CVD risk. Methods: We divided female participants into 3 categories based on their BMI: normal weight control (C) = 24.28, overweight (OW) = 26.28, and non-diabetic obese (NDO) = 39.40. We estimated adiponectin mRNA expression (n = C: 31, OW: 21, and NDO: 67), serum levels (n = C: 44, OW: 29, and NDO:75) and fasting lipid profile. The Kruskal-Wallis and one-way ANOVA tests were applied for between-group analysis. Results: Overall group analysis for adiponectin mRNA levels and serum levels showed no significant differences; however, a significant difference was noted between C and NDO groups at both mRNA (0.0000) and serum (p-value: 0.0032) levels. A significant difference was seen between groups for all lipid profile parameters i.e., HDL (mean: C: 54.67, OW: 47.79, NDO: 42.28), LDL (mean: C: 96.54, OW: 97.73, NDO: 113.17), TC (mean: C: 165.82, OW: 154.92, NDO: 184.84), TG (mean: C: 114.56, OW: 107.40, NDO: 151.78) and VLDL (mean: C: 22.92, OW: 21.47, NDO: 32.73). Adiponectin gene expression correlated negatively with serum adiponectin levels and with HDL and ApoA1 levels. Conclusion: Lower adiponectin levels could contribute to an increased CVD risk in obesity, an effect that could be mediated via changes in HDL. 111474 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Characteristics and Prognosis of Patients with Heart Failure with Recovered Ejection Fraction CARLOS HENRIQUE DEL CARLO1, Antonio Carlos Pereira Barretto1, Mucio Tavares de Oliveira Junior1, Alfredo Jose Mansur1, Antonio de Padua Mansur1, Sergio Jallad1, Juliano Novaes Cardoso1, Andre Barbosa de Abreu1, Jose Antonio Ramos Neto1, Roberto Kalil Filho1 (1) Heart Institute (InCor) University of Sao Paulo Medical School Background: Heart failure (HF) is a clinical syndrome with high morbidity and mortality. Optimal treatment can lead to improvement in ventricular remodeling in HF with reduced ejection fraction (HFrEF). Objective: To analyze the characteristics and prognosis of patients (pts) with HFrEF who evolved with HF with recovery ejection fraction (HFrecEF): left ventricular ejection fraction (LVEF) >40%. We also analyzed the outcomes of pts with any degree of LVEF improvement. Methods: We analyzed the electronic medical records of outpatients treated at a tertiary medical center in Sao Paulo-SP (Brazil) diagnosed with heart failure (ICD-10: I50) in 2017 and followed up until December 31st, 2020. There were included 4068 pts with an initial echocardiogram (ECHO1) presenting LVEF <=40% (HFrEF). Data from a second evolutionary echocardiogram (ECHO2) were analyzed and pts were reclassified into HFrEF, HFrecEF, or any LVEF improvement (LVEF in ECHO2 > ECHO1). The clinical characteristics and prognosis of pts with respect to HFrecEF and those with any degree of LVEF improvement were analyzed. Statistical methods: Mann-Whitney U test, chi-square test or Fisher's exact test, univariate and multivariate logistic regression analysis, and survival using the Kaplan-Meier method (p = Log-Rank). Results: Of the 4068 pts studied, age 61.3 +- 13.4 years, 65% male, with regard to etiology: idiopathic cardiomyopathy (46.6%), ischemic (27.5%), hypertensive (14.2%), Chagas disease (7.6%), valvular (4.2%); the mean initial LVEF: 30.0 +- 6.7%. Comparing LVEF in ECHO1 and ECHO2, 2594 pts (63.8%) showed any degree of LVEF improvement and 1250 (30.7%) evolved with total or partial LVEF recovery. Pts with HFrecEF had a higher initial mean LVEF: 32.2 +- 6.6% vs 29.0 +- 7.5% (p < 0.001). The ECHO2 showed an important improvement in the LVEF among pts with HFrecEF (50.9 +- 7.5% vs 29.4 +- 6.4%, p < 0.001). Female gender, hypertensive and valvular etiologies were associated with HFrecEF, while male gender, chagasic etiology, and history of stroke were independently associated with non-recovery of LVEF. Pts with HFrecEF had lower mortality (16.5% vs 30.1%, p < 0.001). The reduction in mortality was also observed in pts with any LVEF improvement (21.9% vs 33.0%, p < 0.001). Conclusion: HFrecEF was observed in 30.7% of pts with HFrEF and was accompanied by an improvement in prognosis. A reduction in mortality was also observed in pts with any degree of LVEF improvement. 111477 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of the COVID-19 Pandemic on the Incidence of Extra-Hospital Cardiovascular Deaths in Brazilian Capitals ANA CAROLINE DARIVA CHULA1, Ana Caroline Dariva Chula1, Marcia Olandoski1, Elias Teixeira Krainski2, Lucas Henrique Olandoski Erbano1, Bruna Olandoski Erbano1, Raisa Natalia Dotto1, Lucas Baena Carstens1, Nicolle Amboni Schio1, Amanda Zanlorenzi1, Rafaela Lima Camargo1, Jose Rocha Faria-Neto1 (1) Pontificia Universidade Catolica do Parana - PUC PR; (2) Universidade Federal do Parana - UFPR Background: Many countries have reported an increase in the number of out-of-hospital deaths from cardiovascular diseases during the COVID-19 pandemic, which may be due to factors intrinsic to the disease or social conditions arising from the pandemic. Objective: To analyze possible differences in the temporal trend of out-of-hospital cardiovascular deaths during the COVID-19 pandemic in the year 2020 in Brazilian capitals. Method: This is a time series, whose data were collected on the websites based on the Civil Registry Information Center, and from the Influenza Epidemiological Surveillance Information System. On the first website, the numbers of deaths from COVID-19 and deaths from out-of-hospital cardiovascular causes were collected, week by week, from the 2nd to the 35th epidemiological week of 2019 and 2020, in Brazilian capitals. On the second website, data on hospitalizations for COVID-19 in the capitals were collected daily between March and October 2020, by date of first symptoms and by date of hospitalization itself, and tabulated weekly for combination by epidemiological week. The 2020 time series of total out-of-hospital cardiovascular deaths (TMCV-EH) was considered as the outcome. The time series effect of COVID-19 data was tested to explain the variation across the studied weeks of 2020. COVID-19 hospitalization data were tested as potential predictors of MCV-EH, as were death data from COVID-19. The TMCV-EH in the corresponding period of 2019 was used for comparison. Results: There was an increase in the TMCV-EH in 2020 compared to the non-pandemic year of 2019 and a correlation in the variation of these deaths with the COVID-19 data, with a peak in late April and early May when the relative risk, in the sum of the data, reached twice. There was also heterogeneity in the distribution of MCV-EH when analyzing each capital, with a predominance in the north and northeast regions. The highest relative risks stand out, compared to 2019, in peak periods in some capitals such as Salvador with 3.8, Recife with 3.6, Sao Luis with 5.6, Belem with 7.5 and Manaus with 9. 5 times. Rio de Janeiro presented a relative risk in the peak period of 2.2 times and Sao Paulo of 1.6 times. Conclusion: There was an increase in the number of out-of-hospital cardiovascular deaths during the COVID-19 pandemic, in Brazilian capitals. 111486 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of the COVID-19 Pandemic on Hospital Admissions for Acute Coronary Syndromes and Mortality from Cardiovascular Diseases in the State of Sao Paulo MARIANE VENTUROLI FERREIRA BENAVENTE1, Marcia Olandoski1, Jose Rocha Faria Neto1 (1) Pontificia Universidade Catolica do Parana - Escola de Medicina Introduction: During COVID-19 pandemic, several countries reported reduction in hospital admissions for cardiovascular diseases (CVD), including acute coronary syndromes (ACS), in addition to excess cardiovascular mortality due to direct and indirect effects of the pandemic. In Brazil, there are studies demonstrating reduction in hospitalizations, increase in in-hospital lethality and excess deaths from CVD. There are no studies evaluating the impact of the pandemic on hospitalizations and mortality from CVD in the state of Sao Paulo, the country's most populous state, which concentrates the largest number of COVID-19 cases and deaths. Understanding this impact is essential for the implementation of public health strategies to reduce morbidity and mortality from these conditions. Purpose: The aim of this study was to assess the impact of the pandemic on ACS admissions and mortality from CVD in the state of Sao Paulo. Methods: We performed a retrospective observational study by analyzing the number of ACS hospital admissions - angina pectoris (AP) and acute myocardial infarction (MI) and the number of deaths from CVD - MI and unspecific cardiovascular causes (UCVC), in-hospital and at home, between January 1st, 2020, and December 31st, 2021. Data from 2018 and 2019 were used for comparison. Results: In 2020, there was a 10% decrease in hospitalizations for ACS (18% for AP and 4% for MI) compared to 2019. In 2021 reduction was of 12% (27% for AP and 2% for MI). In 2020, there was a 10% decrease in deaths from MI (11% in-hospitals and 7% at home) compared to 2019, while in 2021 there was a 12% increase in the number of MI deaths compared to 2020, 11% in-hospitals and 15% at home, reaching pre-pandemic levels. In 2020, there was a 50% increase in deaths from UCVC (33% in-hospitals and 127% at home) and in 2021 there was an increase of 11% in the number of these deaths, 11% in-hospitals and 10% at home. The decrease in ACS hospitalizations was followed by increase in deaths from MI and UCVC causes in both 2020 and 2021. Conclusion: In the state of Sao Paulo the pandemic had impact reducing ACS hospitalizations and increasing deaths from CVD, specially UCVC and at home, which remained above baseline levels throughout the analyzed period. 111495 Modality: E-Poster Researcher - Non-case Report Category: PSYCHOLOGY The Role of a Psychoeducation Intervention on 1-Yr Follow-Up of Rehospitalization, Quality of Life, and Post Traumatic Growth, in Heart Failure Patients: A Randomized Clinical Trial MARCIA MOURA SCHMIDT1, Filipa Waihrich de Oliveira1, Camila de Matos Avila1, Brenda Pereira Nunes2, Fernanda Lucchese-Lobato3 (1) Instituto de Cardiologia/Fundacao Universitaria de Cardiologia; (2) Hospital Geral de Caxias do Sul; (3) Hospital da Crianca Santo Antonio, Irmandade Santa Casa de Misericordia Background: Heart failure (HF) is a systemic disease characterized by deterioration of the heart. There are high rates of morbidity, mortality, and re-hospitalization. Cardiology Societies recommend the inclusion of self-care in the treatment. Objective: This study aimed to verify whether a psychoeducation intervention can reduce hospital readmissions, improve quality of life, and promote post-traumatic growth in patients with HF at 1-yr follow-up. Methods: Parallel randomized clinical trial study with HF patients from a regional hospital in Southern Brazil. Patients were invited to join the study at their first outpatient appointment after hospital discharge. All participants completed the WHO quality of life (WHOQOL-BREF) and the post-traumatic growth inventory (PGI) questionnaires at both pre- (T1) and 6 months post-(T2) intervention assessments. Randomization envelopes were opened after the first interview. The patients in the control group (CG) continued to carry out their regular outpatient consultations per medical instructions. Patients in the intervention group (IG), in addition to the regular visits, had two additional individual follow-ups, of 1 hour each, with an interval of 7 days in between, to promote health and psychological education. About one year later, hospital readmission was assessed through medical records and phone call patient report. Statistical analyses were performed using SPSS software v. 24.0. Results: A sample of 142 patients was recruited at T1 (72 in the CG and 70 in the IG). While at T2, 19 dropped out, and 123 patients (63 in the CG and 60 in the IG) were reassessed after 315 +- 198 days. The participants were 65% male, with 64 +- 11 years old, 58% had low income and 67% had less than high school. The risk of readmission was reduced by 54% (p = 0.050). There was an improvement in the total quality of life (p = <0.05) and positive psychological growth (p < 0.001) in the IG at T2. Conclusions: The intervention proved to be protective for patients with HF in a regional hospital in Southern Brazil. A 2-session psychoeducational intervention was effective in reducing readmission rates by half compared to the CG, as well as improving quality of life and promoting positive psychological growth. Future brief culturally sensitive psychoeducation programs should be implemented in Brazilian hospitals to improve knowledge about HF and patient self-care, reducing the burden that HF creates to our health system. NCT 04870918. 111496 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Initial Learnings of Prehospital Management of NSTEMI: Report from Mission Delhi DR. CHANDINI SUVARNA1, Praveen Aggarwal1, Ramakrishnan Sivasubramanian1, Sandeep Seth1, Neeraj Parekh1, Sheikh Vamik1, Ambuj Roy1, Ganesan Karthikeyan1, Sandeep Singh1, Rajiv Narang1, Balram Bhargava2, Meenakshi Sharma2 (1) Chandini Suvarna; (2) Praveen Aggarwal; (3) Ramakrishnan Sivasubramanian; (4) Sandeep Seth; (5) Neeraj Parekh; (6) Sheikh Vamik; (7) Ambuj Roy; (8) Ganesan Karthikeyan; (9) Sandeep Singh; (10) Rajiv Narang; (11) Balram Bhargava; (12) Meenakshi Sharma Background: Non-ST-segment elevation myocardial infarction (NSTEMI) are common manifestations of coronary artery disease (CAD) which is the leading cause of death in India. Despite advances in the treatment of ACS, pharmacologic therapy remains underused and is often delayed. Mission DELHI (Delhi Emergency Life Heart Attack Initiative) is a pilot project for pre-hospital thrombolysis using motorbike ambulance service by trained paramedics at the patient's doorstep in a selected geographical area of New Delhi. Objective: We sought to determine the feasibility and safety of prehospital care and risk stratification of NSTEMI. Method: We covered a geographical area of 10-km around our institution. A command center was set up and the patients were required to call a dedicated helpline number. Upon initial screening, a motorcycle ambulance was dispatched to the caller's location. A 12 lead ECG was obtained as soon as possible after first medical contact by paramedic and electronically transmitted to a dedicated command center. Evaluation of the ECG was done by cardiologist. Patients with suspected NSTEACS, administration of platelet aggregation inhibitors, anti-cholesterol drugs and transferred to the emergency department for further diagnostic assessment and therapeutic decision. On site troponin testing was done when needed. Patients with persistent symptoms despite initial therapy may be transferred directly to a catheterization laboratory. Result: A total of 60 NSTACS patients (mean age 57.7 years; 68.3% male) were treated either at home (66.7%), public places (15%), place of work (11.7%) or at small clinics (6.7%). Time taken to reach the patient location and take an ECG was 27.9 +- 8.2 min. Nearly 56.7% of patients received a loading dose of aspirin, clopidogrel and atorvastatin pre-hospital. Nearly two third of patients (46.7%) received medication for HTN, followed by 66.7% of patients given cardiac medications and 60% patients given other medications including antacid/antiemetic. Conclusions: In this study, we have demonstrated the prehospital acquisition and transmission of ECG by paramedics was feasible. An early diagnosis of the majority of cases with NSTEMI and initiation of basic pharmacotherapy was possible prehospitally. Such an early diagnosis and risk stratification could improve outcome, which needs to be assessed in larger studies. 111914 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM SARS-COV-2 Variants and Clinical Outcomes ILIANA REGINA RIBEIRO MENEZES1, Giovanni Possamai Dutra1, Leticia de Sousa Peres1, Nathalia Duarte Camisao1, Mariana Moreno Canario da Silva1, Renata Mexias Abdala Felix1, Thiago Moreira Bastos da silva2, Anna Butter1, Henrique Custodio Goudar1, Bruno Ferraz de Oliveira Gomes1, Joao Luiz Fernandes Petriz1, Glaucia Maria Moraes de Oliveira2 (1) HOSPITAL BARRA D'OR; (2) UNIVERSIDADE FEDERAL DO RIO DE JANEIRO Introduction: There is evidence that the clinical outcomes of COVID-19 vary according to its variants. Given the high risk of infection-related mortality, recognizing the outcomes in each variant may contribute to understanding the severity of the disease. Objective: To evaluate the association of mortality, myocardial injury, lung parenchyma involvement and use of mechanical ventilation, and length of hospital stay with the most prevalent variants of COVID 19 in Brazil. Methods: Patients admitted to an intensive care unit during the COVID-19 pandemic, with an RT-PCR confirmed diagnosis of COVID-19 were included. The following outcomes and clinical features were analyzed in each period: mortality, length of hospital stay, myocardial injury, lung parenchyma involvement, and use of mechanical ventilation (MV). We divided our sample according to periods where some variants were more prevalent: March to October/2020 (beta); November/2020 to July/2021 (P.1); August to December/2021 (delta) and January to April/2022 (omicron). The variables were analyzed using the chi-square test (categorical) and ANOVA (continuous). Results: 1454 patients were included, mean age = 59.8 +- 17.0 years, 62.6% men. Occurred 269 deaths (18.5%) during the study period (mean follow-up = 338 +- 209 days). We observed a greater association with mortality in the beta variant: beta (23%), P.1 (16.6%), delta (16.6%), and omicron (12.1%) with p = 0.015. Myocardial injury was more prevalent with the omicron variant: beta (32.7%), P.1 (49.2%), delta (53.5%), and omicron (60.6%) with p < 0.001. Lung involvement >50% was more common in omicron: beta (13.0%), P.1 (14.3%), delta (13.6%) and omicron (27.6%) with p < 0.001. No difference was observed in MV need. The average length of hospital stay was higher in beta: beta (20.6 days), P.1 (14.3 days), delta (13.5 days), and omicron (9.6 days), p < 0.001. Finally, the Average time of MV use was higher in beta and P.1: beta (21.4 days), P.1 (21.1 days), delta (14 days), and omicron (9 days). Conclusion: The beta variant was associated with greater mortality and length of hospital stay, while the omicron variant was associated with myocardial injury and shorter mechanical ventilation time in patients hospitalized in intensive care for COVID 19. 111523 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING New Non-Invasive Assessment Model of Coronary Lesions by Computer Tomography Fractional Flow Reserve Compared to the Invasive Technique Under Hyperaemic and Basal Conditions DIEGO LOPEZ OTERO1, Alberto Otero Cacho2, Brais Diaz Fernandez1, Maria Bastos Fernandez1, Xoan Sanmartin Pena1, Vicente Perez Munuzuri2, Alberto Perez Munuzuri2, Jose Ramon Gonzalez Juantey1 (1) Universitary Clinical Hospital of Santiago de Compostela, Cardiology. CIBERCV, Santiago De Compostela, Spain; (2) FlowReserve Labs S.L. Santiago de Compostela Purpouse: To validate a new model of Fractional Flow Reserve obtained from a coronary computed tomography angiography (CCTA) (FFRct) (figure 1A), as well as obtaining new emerging parameters, less studied, such as DFFRct , wall share stress (WWS) (figure 1C) and stenosis resistance (SR). Methods: We included patients referred by the chest pain unit for ischemic heart disease screening, selecting for invasive study those with at least one coronary lesion >50% in the CCTA. Patients with unadequate CCTA interpretation were excluded. To eliminate possible biases, the results of the invasive FFR were unknown at the time of applying this new model to obtain the FFRct value. Results: 26 patients (32 lesions) were included. 86.6% were males and a mean age 57.4 +- SD 11.7 years. In most cases, as these were low-risk patients, and critical disease was excluded, a FFR value >0.80 was obtained. To study the correlation between invasive FFR values and those obtained by the computational model, Spearman's r coefficient and R2 were calculated. There were no false negative or positive cases. The correlation was high in all the parameters studied (>0.6), being positive for the FFRct and negative for DFFRct, WWS and SR. The plot in Figure 1D compares the FFRct under steady hyperaemic conditions as a function of the invasive FFR, note the good agreement between the numerical and invasive methods. Conclusions: Our new model was shown to have a good correlation with the invasively measured FFR in this serie of low-medium risk patients. The clinical usefulness of the new parameters in isolation is yet to be determined, but they could be helpful in cases where the FFRct value is in the gray area (0.75 <= FFRct <= 0.8), specially the DFFRct. 111547 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Short Term Outcomes of Chagas Disease Patients Hospitalized Due to COVID-19 EZEQUIEL J ZAIDEL1, Alvaro Sosa Liprandi1, Joaquin Perea1, Matias Ariel Oliva1, Pablo Perel2, Kavita Singh2, Dorairaj Prabhakaran2, Lana Raspail2, Karen Sliwa Hahnle2 (1) Sanatorio Guemes, Buenos Aires, Argentina; (2) World Heart Federation Introduction and aims: Vulnerable patients with chronic Chagas Disease (CD) may have worse outcomes if hospitalized due to COVID-19. As CD is a neglected tropical disease, it is under-represented in international COVID-19 studies. Current data is scarse and with diverse results. The aim of the present analysis was to describe the clinical profile of patients with known chronic CD during COVID-19 hoapitalization and to analyze if CD patients had different clinical outcomes. Methods: WHF Covid-19 and cardiovascular (CV) Disease registry is a unique COVID-19 prospective registry, as it included cases from different continents and economic strata. CD was a specific subgroup of analysis, and different centres mainly from latin america included CD cases in the registry. A conventional descriptive and comparative analysis was performed. Results: A total of 5313 Covid-19 patients were enrolled in 40 hospitals from 23 countries. Among them, 36 were reported as chronic CD cases. The mean age of CD was similar to non-CD patients (56.4 +- 15 vs 57 +- 16 years, p = NS) but the proportion of women was higher (61.1% vs 40.4%, p = 0.011), and had higher rate of baseline heart failure (16.6% vs 5.4%, p < 0.01), prior pacemaker (3.5% vs 1.1%, p < 0.01) and use of CV drugs (75% vs 46.1%, p < 0.01). During hospitalization, the rate of invasive ventilation was higher in CD (8.3% vs 7.5%, p < 0.01), as well as inotropes requirement (8.3% vs 6.8%, p < 0.01), and ventricular arrhythmias (11.4% vs 1.09%, p < 0.01) or heart blocks (11.4% vs 1.4%, p < 0.01). Regarding outcomes, in-hospital death was 5.7% in CD patients and 13.2% in non CD patients (P = 0.38), and no additional deaths occurred at 30 days (0% vs 2.6% in non CD cases, p = 0.054). Conclusions: Altough a limited number of Chagas disease patients were included, they seem to have more CV disease at baseline than non-CD patients, more CV events during COVID-19 hospitalization but similar short term outcomes. 111530 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Impact of the COVID-19 Pandemic on the use of Myocardial Perfusion Imaging for the Assessment of Coronary Artery Disease: A Multicenter Study ANDREA ROCHA DE LORENZO1, Ivanete Costa2, Augusto Santos Tavares3, Gabriel Grossman2, Rafael Lopes3, Ronaldo SL Lima1 (1) Clinica de Diagnostico por Imagem; (2) Hospital Moinhos de Vento; (3) Hospital do Coracao-HCOR Background: The COVID-19 more specifically, the lockdown unquestionable effects on non-COVID healthcare, with reductions in the access to exams and treatments. As myocardial perfusion imaging (MPI) has a well-established role in the evaluation of coronary artery disease (CAD), the diagnosis of CAD might have been affected, with possible long-term adverse consequences. Understanding of the temporal trend of MPI utilization is central in this context. Objective: This study aimed to evaluate the impact of the COVID-19 pandemic on MPI performance and results in 3 Brazilian, Nuclear Cardiology laboratories. Methods: Consecutive patients, with or without known CAD (prior myocardial infarction or revascularization), who underwent stress/rest MPI at 3 Brazilian private Nuclear Cardiology laboratories were studied. The number of tests, indication (diagnostic vs known CAD), frequency of abnormal tests, and frequency of ischemic MPI (those with reversible perfusion defects) were registered in three 30-day time intervals: immediately pre-pandemic, lockdown, and post-lockdown. Variables were compared using Fisher's exact test; p < 0.05 was considered statistically significant. Results: From a total of 1027 MPI studies, 443 were pre-pandemic, 127 were during lockdown (a 71% reduction), and 457 were post-lockdown. Diagnostic tests were 70% of the total before, 61% during lockdown, and 67% after (p = 0.05). The frequency of abnormal MPI tests increased in patients without known CAD in the lockdown period, returning to prior levels after lockdown (11%, 19%, and 11%, p = 0.05), although ischemic tests remained stable (7%, 9%, and 8%). Conclusions: A large reduction of MPI performance occurred during lockdown, with less diagnostic tests. There was no significant difference in the frequency of myocardial ischemia among the 3 intervals, although abnormal MPI tests increased during lockdown in patients undergoing MPI for diagnostic reasons. The altered pattern of MPI utilization caused by the pandemic might have future effects on CAD diagnoses, and therefore should be further and continuously assessed. 111536 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The Perception of a Group of Parliamentarians on Cardiovascular Diseases and Their Impact on Public Health in Brazil SORAYA ARAUJO1, Patricia Vieira2, Andrea Bento3, Carolina Cohen3, Regina Prospero4, Amira Awada4, Sonia de Castilho5, Vanessa Pirolo Vivancos6 (1) Cardiovascular Advocacy Group; (2) Brazilian Association of Family Hypercholesterolemia; (3) Collaborate with the Future; (4) Rare Lives Institute; (5) ADJ Diabetes Brazil; (6) Botucatuense Association of Diabetic Care The Cardiovascular Disease Advocacy Group (GAC) promoted a campaign of Cardiovascular risk awareness named "Faca de Coracao - Teste seu Risco Cardiovascular", as a part of the campaign for World Heart Day. Our group applied a poll to stakeholders at the Legislative Assembly of the State of Sao to mobilize one of the critical stakeholders to this day. This type of approach provides quick evidence of knowledge from the people who are responding and, at the same time, provokes reflections on the subject. The aim of this study was to verify the perception of parliamentarians about cardiovascular diseases (CVD) and their impact on public health in Brazil. Method: A poll conducted by the GAC in the Legislative Assembly of Sao Paulo, from 06/09 to 30/08 of 2021 was applied. The poll consisted of eleven multiple-choice questions (five questions about their health status; two questions about public policies; four questions about specific knowledge of CVD) available on the Googles Forms platform. The questions were presented to the 94 parliamentarians who compose the Legislative Assembly of Sao Paulo (LASP) in virtual visits, witnessed and sent by WhatsApp and e-mail. A descriptive analysis was performed. Results and conclusions: Of the 94 members within a current mandate in the Legislative Assembly, 70 responded to the poll. 84,3% were male; 62,9% aged 36 to 59y; 18,6%, 18 to 35y; and 18,6% aged >60y. In the self-report health status, all are non-smokers, 74% practice physical activity; 52,9% made health check-up; 80% know about their cardiovascular risk; 14,3% has hypertension; 4,3% High Cholesterol, 2,9% Diabetes and 1,4% Obesity. 42% be a part of any collegiate of parliamentarians at LASP to find the best strategies to promote health. Most respondents demonstrate a good knowledge of cardiovascular disease. It is very worrying to note that 91,4% do not believe that the current public policies are effective in the management and control of CVD. However, this is the first step to changing this scenario. 111548 Modality: E-Poster Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Arterial Stiffness Caused by Hypertension Leads to Baroreflex Dysfunction MARIANO DUARTE1, Mariano Duarte2, Analia Aquieri1, Javier Coyle1, Claudio Yaryour3, Carlos Reyes Toso2 (1) Laboratorio Hipertension Arterial, Hospital de Clinicas Facultad de Medicina UBA; (2) Laboratorio de Fisiopatologia Cardiovascular UA 2 Facultad de Medicina UBA; (3) Division Urgencias Hospital de Clinicas Facultad de Medicina UBA Introduction: The rapid regulation of blood pressure allows the continuous adaptation of the cardiovascular system. This function is carried out by baroreflex (BR). Despite the hypertensive (HT) damage to the arterial wall and BR structures are located within it, the impact of hypertension (HYP) on the BR function has not been fully studied. We hypothesized that HYP has decreased BR function caused by increased arterial stiffness (AS). Materials and methods: In prospective study, 101 patients over 65 years of age were included; G1: HT G2: Normotensive (NT). BR function: A continuous rhythm strip in lead DII of electrocardiogram and the Valsalva maneuver was performed. Chronotropic response at the end of the test was established by the lowest R-R recorded up to 5 beats post-Valsalva. According with AHA, BR function was established by the greatest variation in heart rate (smallest R-R) within 5 immediate beats over Valsalva. Results 2 populations: A-BR Nomofunction: increase 10 and 30 beats. B-BR hypofunction, increase <10 beats. Assessment of AS by means of pulse wave velocity (PWV): It is performed by Complior System device, the "gold standard" for the non-invasive measurement. Results: 101 patients (43 men) were studied, 76 of them were HT (147.2 +- 15.7 mmHg) and the rest NT (130.2 +- 10.8 mmHg) p < 0.05. BR hypofunction was observed in 60 of the 76 HT and only in 3 of the 25 NT. PWV was higher in the HT vs. NT (10.54 vs 8.58 m/s) p < 0.001. Conclusions: As hypothesized, 8/10 in G1 had decreased BR function and only 1/10 in G2. Best predictors of BR hypofunction were sought by multivariate analysis were HYP and AS. So, AS could be one of the causal links between HYP and BR hypofunction and would explain the HT baroreceptor desensitization. 111558 Modality: E-Poster Researcher - Non-case Report Category: ANTICOAGULATION Treatment Satisfaction and Convenience with Edoxaban and Vitamin K Antagonists in Patients with Atrial Fibrillation After Transcatheter Aortic Valve Replacement: An Analysis of the ENVISAGE-TAVI AF Trial CHRISTIAN HENGSTENBERG1, Nicolas M. Van Mieghem2, Rosa Wang3, Xiaomei Ye4, Ling Shi4, Shien Guo4, Cathy Chen3, James Jin3, Xin Ye3, Martin Unverdorben3, George Dangas5 (1) Department of Internal Medicine II, Division of Cardiology, Vienna General Hospital, Medical University, Vienna, Austria; (2) Department of Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, the Netherlands; (3) Daiichi Sankyo, Inc., Basking Ridge, NJ, USA; (4) Evidera PPD, LLC, Bethesda, MD, USA; (5) Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York, NY, USA Introduction: ENVISAGE-TAVI AF (NCT02943785; N = 1426) was a randomized, open-label trial that compared edoxaban vs VKAs in patients with atrial fibrillation (AF) after transcatheter aortic valve replacement (TAVR). Noninferiority was shown with edoxaban vs VKAs for the primary endpoint, net adverse clinical events. The effect of edoxaban or VKA-based therapy on patient-reported treatment satisfaction remains unknown. Objective: To assess patient-reported treatment satisfaction and convenience with edoxaban vs VKAs in patients with AF after TAVR. Methods: The Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2) is a validated patient-reported outcome instrument that was used to assess patients' satisfaction and convenience with their anticoagulant treatment. A mixed-effect model for repeated measures assessed the least squares mean difference (LSMD) in PACT-Q2 scores between VKA-treated patients. Cohen's effect size (ES) evaluated clinical meaningfulness of the differences, defined as ES >= 0.2. Results: A total of 1107/1426 (77.6%) patients (edoxaban, n = 585; VKA, n = 522) had evaluable PACT-Q2 data and were included in this analysis. VKA-treated patients had similar baseline characteristics. Edoxaban-treated patients reported significantly higher overall PACT-Q2 scores for treatment satisfaction than VKA-treated patients (LSMD [95% confidence interval], 6.1 [4.5-7.7], P < 0.05), with a clinically meaningful difference (ES, 0.4 [0.3-0.5]). Results were similar in the convenience dimension . Conclusions: ENVISAGE-TAVI AF patients found edoxaban to be more convenient and had greater treatment satisfaction than those who received VKAs. For patients with AF after TAVR, edoxaban may elicit an improved patient experience compared with VKAs. 111569 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of the COVID-19 Pandemic on Acute Myocardial Infarctions Admissions and Outcomes (2020-2021): Report from Large Tertiary Cardiac Centre FATHIMA AAYSHA AAYSHA CADER1, Ishmum Zia Chowdhury2, Syeda Rifat Mahmud1, Isha Abdullah Ali1, Saidur Rahman Khan1 (1) Ibrahim Cardiac Hospital & Research Institute; (2) BIRDEM General Hospital Introduction: There is little data from South Asia on the impact of the COVID-19 pandemic on acute myocardial infarctions (AMI) admissions and outcomes, particularly in the two years following the onset of the pandemic. Objective: We aimed to compare AMI admissions and outcomes over two time periods since the onset of the pandemic at a tertiary cardiac care centre with catheterization laboratory facilities and referrals from across the country. Methods: In this cohort study conducted at our tertiary cardiac centre, we collected and compared data of all patients diagnosed and admitted with AMI over two time periods: between March-August 2020 and March-August 2021. Patient demographics, diagnostic and therapeutic strategies and in-hospital outcomes were statistically analysed and compared by the student's t test and chi-square tests, as appropriate. Results: A total of 380 AMI admissions were included, 82 (21.6%) in 2020 and 298 (78.4%) in 2021 over the same time periods. Significantly more men presented in both years (69.5% and 83.2% in 2020 and 2021 respectively; p = 0.005). No significant differences in cardiovascular risk factors or type of AMI were seen across both time periods (49.7% vs 52.4% STEMI in 2020 vs 2021). Late presentation of STEMI was 30.5% vs 23.2% in 2020 and 2021 respectively (p = 0.13). 35.9% were vaccinated against COVID19 in 2021 (p < 0.001). Significantly more patients developed cardiogenic shock (40.2% vs 23.8% (Odds Ratio [OR] & 95% confidence interval [CI] 2.15 (1.29-3.61); p = 0.003); heart failure (76.8% vs 57.4%; OR 2.46 (1.40-4.32); p = 0.001), cardiac arrest (19.5% vs 9.7%; OR 2.25 (1.15-4.38); p = 0.015) and required ventilation (19.5% vs 9.1%; OR 2.43 (1.24-4.78); p = 0.008) in 2020, as compared with 2021. In-hospital mortality was numerically higher in 2020 (17.1% vs 9.7%; OR 1.91 (0.96-3.81); p = 0.063). AMI patients were significantly less likely to undergo coronary angiography (54.9% vs 71.1% for 2020 vs 2021; p = 0.005) and percutaneous coronary intervention (35.4% vs 44%; p = 0.001) during index admission in 2020. 45% of STEMI patients were given fibrinolysis overall, with fewer in 2020 as compared with 2021 (20.9% vs 47.2%). Conclusion: In the immediate aftermath of the pandemic, fewer patients presented with AMI in 2020, as compared with similar time periods the next year, in 2021. Significantly fewer patients underwent angiography and PCI in 2020. AMI patients had improved outcomes in 2021, as compared to 2020. 111588 Modality: E-Poster Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Linear and Nonlinear Analyzes of Autonomic Modulation in Controlled and Uncontrolled Resistant Hypertensives TATIANE DE AZEVEDO RUBIO1, Bruno Rodrigues1, Silvia Elaine Ferreira-Melo1, Lucia Helena Bonalume Tacito2, Jose Fernando Vilela-Martin2, Moacir Fernandes de Godoy2, Heitor Moreno-Junior1, Juan Carlos Yugar-Toledo2 (1) University of Campinas - UNICAMP; (2) Faculty of Medicine of Sao Jose do Rio Preto -FAMERP Among the blood pressure (BP) regulation mechanisms in RHTN, the expression of autonomic modulation plays an important role. Linear and non-linear analyzes of heart rate variability (HRV) assess the autonomic modulation of the cardiovascular system. Resistant hypertensive patients may present with autonomic dysfunction with different degrees of impairment. The objective of the present study was to evaluate the impairment of the autonomic function of controlled and uncontrolled resistant hypertensive patients, as well as those using beta-blockers. Assessments of autonomic function were performed in 49 resistant hypertensive patients aged between 53 and 82 years. Results: Uncontrolled RHTN patients (U-RHT) present a reduction in HRV and greater expression of sympathetic activity in relation to parasympathetic activity, demonstrated through a statistically significant reduction of the variables SDNN, RMSSD, SD1 and SD2 when compared to the group (C-RHT). In addition, despite the use of beta-blockers, both in RHTN + beta-blockers (RHT+BB) and U-RHT patients, the autonomic balance shows negative changes, that is, lower HRV, compared to the controlled RH group. Conclusion: RHTN patients present a reduction in HRV due to the occurrence of a reduction in parasympathetic activity and a relative increase in the sympathetic component. These results corroborate the importance of interventions on the autonomic nervous system. 112313 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Association of Biomarkers with Mortality in Patients Hospitalized for COVID-19 NATHALIA DUARTE CAMISAO1, BRUNO FERRAZ DE OLIVEIRA GOMES1, JOAO LUIZ FERNANDES PETRIZ1, GLAUCIA MARIA MORAES DE OLIVEIRA2, ANNA BUTTER1, HENRIQUE CUSTODIO GOUDAR1, RENATA MEXIAS ABDALA FELIX1, THIAGO MOREIRA BASTOS DA SILVA2, MARIANA MORENO CANARIO DA SILVA1, LETICIA DE SOUSA PERES1, ILIANA REGINA RIBEIRO MENEZES1, GIOVANNI POSSAMAI DUTRA1 (1) Hospital Barra D'or; (2) UNIVERSIDADE FEDERAL DO RIO DE JANEIRO (UFRJ) Introduction: The pandemic caused by the SARS-Cov-2 virus brought the need for and importance of identifying biomarkers that may indicate a worse prognosis and an increase in the long-term mortality of these patients. Objective: Identify biomarkers associated with long-term death in patients hospitalized by COVID-19. Methods: Retrospective study with hospitalized patients with a confirmed diagnosis of COVID-19. The following biomarkers, collected during hospitalization, were analyzed: d-dimer (admission, peak, and discharge), ultrasensitive troponin (admission and peak), C-reactive protein (admission and peak), and platelet count (admission and peak). We used the ROC curve and the area under the curve (AUC) analysis to determine the biomarkers with the best association with all-cause mortality. Results: A total of 1454 patients were included, mean age of 59.8 +- 17.0, 62.6% were men. There were 269 deaths (18.5%) during the study period (mean follow-up = 338 +- 209 days), and 44.7% of patients had myocardial injury. We observed that the highest AUC was obtained with the discharge d-dimer (AUC = 0.900) and the peak d-dimer (AUC = 0.870). The cutoff point proposed by the Youden index was, respectively: 1945 ng/dL (sensitivity 89%/specificity 73%) and 1987 ng/dL (sensitivity 81%/specificity 88%). Conclusions: We observed a high association of mortality (in and out of hospital) with the peak d-dimer obtained before hospital discharge. This data highlights the need for attention to patients who present high levels of this biomarker at the hospital discharge and may indicate the need for preventive therapies for thromboembolic events. 111595 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Exercise Oscillatory Ventilation Prevalence and 2-Year Mortality Prediction in Chronic Heart Failure Patients: Are There Differences between Ben-Dov, Corra, and Leite Definitions? MARLUS KARSTEN1, Gustavo dos Santos Ribeiro2, Luis Fernando Deresz3, Elisabetta Salvioni4, Dominique Hansen5, Piergiuseppe Agostoni6 (1) Universidade do Estado de Santa Catarina (UDESC); (2) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (3) Universidade Federal de Juiz de Fora (UFJF); (4) Centro Cardiologico Monzino (CCM); (5) Hasselt University (UHASSELT); (6) University of Milan (UNIMI) Background: Exercise oscillatory ventilation (EOV) is an abnormal phenomenon observed in chronic heart failure (HF) patients and is associated with a greater risk of adverse cardiovascular events. Purpose: To compare the EOV prevalence of 3 EOV definitions and to predict 2-year all-cause mortality in HF patients. Methods: Cardiopulmonary exercise test data from 233 HF patients were analyzed. Two blinded reviewers identified EOV according to the definitions of Ben-Dov, Corra, and Leite. Prevalence data were compared by the Cochran's Q test and McNemar post hoc test. The relative risk of death and Kaplan-Meier survival analysis were applied in a 2-year follow-up. Sensitivity and specificity to predict 2-year mortality were determined by the receiver-operating characteristic curve. Results: EOV prevalence was 16.7, 17.5, and 8.4% by Ben-Dov, Corra, and Leite's definitions. There was no difference in EOV prevalence between Ben-Dov and Corra. Both were different from Leite (p < 0.01). The 2-year death risk was 1.9 (1.0-3.7), 2.8 (1.6-5.2), and 2.0 (0.9-4.3) applying Ben-Dov, Corra, and Leite's definitions. Table 1 shows the sensitivity and specificity to predict 2-year mortality. Conclusion: EOV definition's choice directly affects the number of EOV cases. Ben-Dov and Corra definitions seem to have similar predictive power. Corra definition shows better sensitivity to predict 2-year mortality. 111589 Modality: E-Poster Researcher - Non-case Report Category: PSYCHOLOGY Line of Care for Value-Based Surgical Valvular Disease: The Influence of Surgery in the Physical, Psychosocial and Mental Health Improvement Aspects from the Patient's Perspective SIRLEI PEREIRA NUNES1, Sirlei Pereira Nunes1, Bellkiss Wilma Romano1, Flavio Tarasoutchi1, Danielle Misumi Watanabe1 (1) InCor - Instituto do Coracao do Hospital das Clinicas da FMUSP Introduction: The high mortality from cardiovascular diseases compromises significantly the Quality of Life (QoL) of patients (pacs) in all aspects, especially physical, psychosocial and mental health, making it necessary to rethink care in this population, implementing care, carried out and shared by a team of multidisciplinary. Objective: Verify the surgical influence the valve on the improvement of QoL at perspective of pacs. Method: Retrospective randomized observational longitudinal study of pacs surgical valve disease from a public health institution in the State of Sao Paulo, by a multidisciplinary team: clinical and surgical cardiologists, nurses, psychologists and others. Psychology assessment occurred in three moments: preoperative(preop), postoperative (posop) in the nursery ward and postoperatively (posop B), six months after the procedure from hospital discharge. 995 pacs were evaluated in preop, 517 posop in nurse and 144 pacs in posop B, March/2018 to February/2020, using semistructured interview technique and the SF 36 instrument that measures QoL from the individual's perception of their general health from 0 to 100. Results: The results showed an improvement in QoL the SF 36, emphasizing physical, social, emotional and mental health aspects, see table 1(one). Conclusion: Value-based care through the surgical valve disease line of care was effective in providing pacs with na improvement in their QoL. 111644 Modality: E-Poster Researcher - Non-case Report Category: NURSING Factors Associated with High Time Spent in Sedentary Behavior in Nursing Students FERNANDA CARNEIRO MUSSI1, Flavia Silva Ferreira1, Maria Cecilia Gallani4, Jules Ramon Brito Teixeira2, Thiago Ferreira Sousa3, Francisco Jose Gondim Pitanga5, Fernanda Michelle Santos Silva1, Brenda Silva Cunha1 (1) Escola de enfermagem, Universidade Federal da Bahia, Salvador, Bahia, Brazil.; (2) Escola de Enfermagem, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil.; (3) Centro de Formacao de Professores, Universidade Federal do Reconcavo Baiano, Amargosa, Bahia, Brazil; (4) Faculte des sciences infirmieres, Universite Laval, Quebec, Quebec, Canada.; (5) Escola de Educacao Fisica, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Introduction: Sedentary behavior (SB) has been associated with chronic disease and all-cause mortality even in sufficiently active people. College students are referred to as a group exposed to SB, but little is known about this behavior in nursing students. Objective: To estimate the amount of time nursing students, spend in sedentary behavior in their daily lives and to examine the association between time in sedentary behavior and sociodemographic, academic, and behavioral variables. Method: Cross-sectional study, with 286 university students. Pearson's Chi-square or Fisher's Exact test and Multiple Logistic Regression were used. Sedentary behavior >=8 hours per day (h/day) was common and risks were corrected by the Delta estimation method, obtaining the prevalence ratio and 95% confidence interval. A statistical significance of 5% was adopted. Results: Sedentary behavior >=8h/day was identified for 53.5%. Older college students were 33.0% less in sedentary behavior >=8h/day compared to younger students; with >=3 hours of the out-of-class study showed 1.23 times more sedentary behavior >=8h/day compared to those with <3 hours; with >=4 subjects showed 1.58 times more sedentary behavior >=8h/day compared to those with <=3; insufficiently active showed 1.25 times more sedentary behavior >=8hr/day compared to those who met the recommendation and who used sleep medications showed 1.46 times more sedentary behavior >=8h/day compared to those who did not. Conclusion: It is necessary to combat sedentary behavior especially in younger college students, with accumulation of subjects, sleeping drugs, and insufficiently active. 111660 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY An Electrocardiographic Index in Aortic Root Enlargement and Ventricular Hypertrophy with Phi-Guided Chest-Wall Thickness Derived Measure JOSE RAMON LANZ-LUCES1, Fernando Augusto Alves da Costa11, Luis Fernando Escobar Guzman2 (1) Instituto Paulista de Doencas Cardiovasculares (IDPC); (2) Hospital Beneficencia Portuguesa de Sao Paulo (BP) Introduction: Dilated aortic root (DAo) is a risk for cardiovascular events besides left ventricular hypertrophy (LVH). There is a lack of a useful index pondering both scenarios. Objective: To evaluate an electrocardiographic index in DAo and LVH comparing echocardiographic consensus values and those derived using the wall chest thickness (CT). Methodology: 631 patients, 236 hypertensive (HT) and 395 non-hypertensives (nHT), the diameter of the aortic root was based on the golden number (Phi) and the derived formula CT x 1.33 = Ao, using a cut-off >15% for enlargement. The index stemmed from the R + S amplitude sum in leads D1 + D2 + D3 and for values <23 mm. The index was also compared with Cornell and Sokolow-Lyon-Rappaport indexes and stablished criteria for Dao and LVH using T-test and CH2 test as appropriate. Results: The index prevalence was similar between groups (HT:42.7 vs. nHT: 37%, p = 0.15). There were differences in echocardiographic measurements (aorta, septum, posterior wall, and ventricular mass, p < 0.05). The index failed to be related to LVH, on the contrary it was associated to DAo derived from CT in the general population (OR: 2.189 CI95%: 1.546-3.100, p < 0.001) and in NTH (OR:3.010 CI95%: 1,869-4.847). Similar results for actual Dao criteria in the NTH (OR:3.078 CI95%:1.224-7.738, p = 0.012). Cornell index showed similar odds however, the test-sensibility was far less than the novel index, 8.4% vs 71.2%. Conclusion: This novel index was advantageous separating those with a DAo based CT measure along with literature consensus criteria for non-hypertensive patients. 111670 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Coronary Artery Bypass Graft or Percutaneous Coronary Intervention in Young Patients with Acute Coronary Syndrome and High Atherosclerotic Load: A Paired Analysis by Propensity Score LUIZ SERGIO FERNANDES DE CARVALHO1, Alice Pacheco Santos4, Ana Carolina Machado Rodrigues da Cunha4, Guilherme Albuquerque Gruber4, Ana Claudia Cavalcante Nogueira2, Alexandre Anderson de Souza Munhoz Soares2, Gustavo Alexim3 (1) Clarity Healthcare Intelligence; (2) Instituto Aramari Apo; (3) HRS-DF - Hospital Regional de Sobradinho do Distrito Federal; (4) UCB - Universidade Catolica de Brasilia Introduction: The epidemiology of acute coronary syndromes (ACS) has gone through dramatic changes in recent decades, with an increase in its incidence in young individuals (under 55 years, ACSy) and a relative decrease in older individuals (ACSo). The management of ACS in young patients with moderate to high atherosclerotic load after the primary event still needs elucidation, since these individuals retain a long life expectancy. Objective: To compare clinical outcomes and cost of care in individuals with premature CAD and moderate to high atherosclerotic load undergoing Coronary Artery Bypass Graft (CABG) or percutaneous coronary intervention (PCI). Method: The study population consisted of the retrospective B-CaRe:QCO assortment, which includes all patients admitted with ACS in public hospitals in Federal District between 2013 and 2015 and who underwent cardiac catheterization with SYNTAX score >28. Outcomes were adjudicated with death certificates and medical record data. The primary clinical outcome was composite by CV death and recurrent ACS (MACE), followed by secondary endpoints: all-cause death and AMI. To assess indirect and direct costs, we evaluated, in international dollars (Int$) per year, the cost of lost productivity due to illness and death, ambulatory costs, and costs of new hospitalizations. Multivariate and propensity score paired (PEP) analyses were performed. Results: Among 1088 subjects (111 treated by CABG and 977 with PCI) aged <55 years accompanied for 6.2 (IQR 1.1) years, 304 primary events were observed. MACE was observed in 20.7% of the CABG group and 28.8% of the PCI group (p = 0.037). All-cause deaths were seen in 8.1% of the CABG group and 6.6% (p = 0.450) of the PCI group. AMI was seen in 6.3% of the CABG group and 15% of the PCI group (p = 0.014). On multivariate analysis, PCI was associated with higher hazard ratio (HR) for MACE, 1.227(95% CI 1.004-1.499; p = 0.04577), and in PEP HR = 1.268 (95% CI 1.048-1.548; p = 0.0271) compared to the CABG group. Although we observed no statistical differences in direct costs, the cost of lost productivity was higher in the PCI group (Int$4,511 (IQR 18062)/year vs Int$3,578 (IQR 13198)/year; p = 0.049] compared to CABG. Conclusion: In younger, high-atherostatic load ACS patients, the surgical approach is associated to lower occurrence of major long-term adverse cardiovascular effects, besides being associated to lower indirect costs. 111703 Modality: E-Poster Researcher - Non-case Report Category: PERIOPERATIVE EVALUATION Myocardial Injury After Non-Cardiac Surgery Prediction using Machine Learning BRUNO FERRAZ DE OLIVEIRA GOMES1, Thiago Moreira Bastos da Silva2, Leticia de Sousa Peres1, Iliana Regina Ribeiro Menezes1, Nathalia Duarte Camisao1, Mariana Moreno Canario da Silva1, Renata Mexias Abdala Felix1, Giovanni Possamai Dutra1, Anna Butter1, Henrique Custodio Goudar1, Joao Luiz Fernandes Petriz1, Glaucia Maria Moraes de Oliveira2 (1) Hospital Barra D'Or; (2) Universidade Federal do Rio de Janeiro Background: Myocardial injury in non-cardiac surgery (MINS) occurs in 10-25% and increases mortality in 30 days. Prediction tools can help in the creation of preventive strategies. Methods: Retrospective cohort study including all non-cardiac surgery patients admitted to a postoperative care unit who stayed at least one night in this unit and had at least one measurement of high-sensitive cardiac troponin. Clinical characteristics and the occurrence of MINS were assessed. All variables were included in the classification tree statistical model, a machine learning method, where variables with p < 0.05 were included in the analysis. Results: 2230 patients were included, mean age = 63.7 +- 16.2 years, and 55.6% women. The prevalence of MINS was 9.4%. The classification tree is available in Figure 1. The variables selected by the model were: age, RCRI score, high-risk surgery, previous myocardial infarction, and creatinine. This model has an accuracy of 90.6%. Conclusion: Age, RCRI score, high-risk surgery, previous myocardial infarction, and creatinine were predictors of MINS and were included in the classification tree. This model exhibited high accuracy and may be useful in the early identification of these patients. 111681 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Epidemiological Profile of Patients with Heart Diseases with Indications for Palliative Care MARIA TERESA CABRERA CASTILLO1, MILENA DAVI NARCHI1, FLAVIA CUNACIA D'EVA1, ROBERT TANAKA1, ADRIANA FUCCI1, DEBORA CLOTILDE CAROLLA1, LUISA MURAKAMI1, FARID SAMAAN1, RUI FERNADO RAMOS1, GUSTAVO BERNARDES DE FIGUEIRDO OLIVEIRA1, ARI TIMERMAN1 (1) INSTITUTO DANTE PAZZANESE DE CARDIOLOGIA Introduction: Cardiovascular disease (CVD) is the leading cause of death in Western countries, with heart failure being the final pathway of heart disease. Despite this, few patients are referred for Palliative Approach (PA). There is no consensus about the indication or the right time to refer patients to PA, whose main objective is to improve the patient's quality of life. Objective: Characterize the epidemiological profile of patients with heart diseases with indication for PA in a hospital specialized in cardiology. Methods: This is a cross-sectional study with analysis of 554 patients included for PA from Feb 2018 to Feb 2022. Frequency, median, percentage, mean, maximum and minimum value were used for statistical analysis. Results: The sample comprised of 554 patients (P), for PA 270(57%) were male, mean age 71 +- 14 years, 179(37%) Catholic, 91(20%) Evangelical, With most frequent medical history of arrhythmia 242(51%), ventricular dysfunction 297(62%), Coronary artery bypass graft surgery 109 (23%) and stroke 175(15%). The most frequent clinical complains were: Dyspnea 329(59.30%), Lower limb edema 96(17.39%), diagnosis at the time of PA was renal failure 351 P (74.4%) and of these 148 (31%) needed hemodialysis, Heart failure 177(31.9%) (HF), Sepsis/Septic shock 146(26,3), stroke 113(20%). The mean ejection fraction was 40%. As for performance in activities of daily living we used the Palliative performance Scale (PPS) where 282 (71,1%) needed life support. We evaluated the prognosis with the PPI scale, 345(56.8%) with high short-term mortality. Regarding treatment, 277(58,7%) of patients with PA had CVC, 277(58.7%) received broad spectrum antibiotics, 196(41.5%) dobutamine, 138(30%) noradrenaline, 164 (34.7%) on mecanichl ventilation 130(27.5%) on hemodialysis 116(24.6%) sedated, 81 (8%) with IAP. Among these patients 295(52.9%) died during hospitalization and 126 (22%) were able to be discharged. Only 26(4.7%) did not accept the PA protocol, the most frequent site of the PA was 245(51.1%) in the ICU, followed by the ward with 227 (48%) P. Conclusion: In our sample we identified that patients with heart disease in PA still receive futile interventions and therapies, and the most frequent site of palliation is the ICU. This shows a later indication for PC, in patients with advanced HF and at the end of life. Strategies and institutional protocols are needed for an earlier indication, in order to promote integral care and better qualy of life. 111684 Modality: E-Poster Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Maternal Supplementation of Omega-3 is Safe for the Fetal Heart? a Randomized Clinical Trial PAULO ZIELINSKY1, Paulo Zielinsky1, Julia Foresti1, Debora Raupp1, Daniela Babinski Guimaraes1, Kelly Zucatti1, Vitoria Gomez1, Vitoria Aragon1, Izabele Vian1, Eduarda Bonamigo1 (1) Institute of Cardiology of Rio Grande do Sul (IC/FUC) Omega-3 (DHA) has been reccomended to adequate fetal development during gestation. Since it is a substance with intense anti-inflammatory action, such as dietary polyphenols, its effects upon the fetal heart and circulation are unknown and safety of its administration during gestation is not yet established. This study was designed with the purpose to investigate if maternal supplementation of omega-3 is followed by alterations of flow dynamics on fetal ductus arteriosus, at the final trimester of pregnancy, through a double blind, placebo-controlled, randomized clinical trial by groups. Pregnant women between gestational 27 and 28 weeks without cardiac alterations at fetal echocardiography were included, with exclusion of those taking nonsteroidal anti-inflammatory drugs or other substances with this effect, such as polyphenol-rich foods. The intervention group received supplementation of 450 mg of DHA/day in gastroresistent capsules and was compared to the placebo group, after 8 weeks. The participants in both groups were submitted to fetal Doppler echocardiography, assessment of dietary polyphenol and omega-3 consumption, as well as serum prostaglandin levels. Intergroup and intragroup data were evaluated. The study ended up with 24 participants in each group. After 8 weeks, Doppler echocardiographic parameters of ductal flow and serum prostaglandin levels in both groups did not show significant intergroup differences (systolic velocity: p = 0.59; diastolic velocity: p = 0.53; pulsatility index: p = 0.29; serum prostaglandin levels: p = 0.40) The expected intragroup differences as a result in increase in gestational ages were present. The results of this study suggest that omega-3 supplementation is safe at the final third of pregnancy, not causing alterations in the dynamics of the fetal ductus arteriosus flow, at the doses used, despite its potential anti-inflammatory action. 111685 Modality: E-Poster Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Gene Therapy with Mirna-205 Selected from Aerobic Exercise Training Promotes Cardiovascular Protection in Arterial Hypertension TIAGO FERNANDES1, Fernanda Roberta Roque1, Vander Jose Neves2, Joao Lucas Penteado Gomes1, Andre Casanova Silveira1, Graziela Amaro Vicente Ferreira Saraiva4, Suliana Mesquita Paula3, Camila Paixao Jordao5, Rodrigo Souza4, Luciana Venturini Rossoni3, Maria Urbana Pinto Brandao Rondon4, Edilamar Menezes Oliveira1 (1) Laboratory of Biochemistry and Molecular Biology of Exercise, School of Physical Education and Sport, University of Sao Paulo; (2) President Tancredo de Almeida Neves University Center; (3) Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo; (4) School of Physical Education and Sport, University of Sao Paulo, Sao Paulo; (5) Heart Institute Arterial hypertension (AH) is a multifactorial syndrome characterized by high levels of blood pressure. Aerobic exercise training (ET) has been used as an important non-pharmacological treatment of AH, since it mitigates cardiovascular remodelling and blood pressure; however, the mechanisms involved are poorly understood. Our analysis of the miRNA's expression profile by microarray, we selected the miRNA-205 for being one of the most differentially expressed miRNAs in AH, being neutralized by ET, and for targeting many genes involved in the vascular process. Therefore, we aim to evaluate the therapeutic potential of ET and gene therapy with AAV9-miRNA-205 treatment in spontaneously hypertensive rats (SHR), and the circulating miRNA-205 expression in AH patients. SHR aged 6 months and the respective controls Wistar Kyoto (WKY) were divided into four experimental groups (n = 7/group): SHR, trained SHR (SHR -T), WKY and trained WKY (WKY-T). The swimming ET consisted of 10-week, 1 x day/5 x a week/10 weeks. ET promoted reduction in blood pressure in SHR and resting bradycardia in trained animals. We observed a reduction in VO2max accompanied by cardiac hypertrophy and skeletal muscle atrophy. Moreover, these animals showed an increase in wall:lumen ratio of the femoral artery and muscle arteriole. ET corrected these changes in the peripheral vessels. AH increased 300% miRNA-205 levels by real-time PCR paralleled with a decrease of target genes VEGF, Akt, Bcl-2, eNOS, Itga5, TGFa and p70S6K levels by western blot compared to WKY group in skeletal muscle. In contrast, ET counteracts miRNA-205 and target genes levels toward control. Also, we used an adeno-associated virus 9 (AAV9) delivery methods to inhibit miRNA-205 in cardiovascular and muscle systems. Interestingly, AAV9-mediated miRNA inhibition (single systemic injection of AAV: 2 x 1012 viral genome particles) reduced AH-induced high levels of blood pressure compared to AAV-9 control around 25 mmHg in SHR. Indeed, miRNA-205 inhibition attenuated cardiac remodelling in SHR. In AH patients, the circulating levels of miRNA-205 were higher when compared to the normotensive group. Together, these results support the hypothesis that the morphofunctional changes arising of AH may be regulated by miRNAs and target genes; and ET participates in restoring the cardiovascular system. Thus, AAV9-mediated miRNA-205 inhibition appears as perspectives for the potential therapeutic use of miRNAs in the treatment of AH. 111930 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS 2016 Left Ventricular Diastolic Function Guideline Have Better Prognostic Value Than 2009 Guideline in Patients with Acute Coronary Syndrome RAFAEL MODESTO FERNANDES3, Carolina Aslan Ribeiro Brito5, Carolina Costa da Silva Souza5, Vitor Queiroz de Castro Souza5, David Le Bihan4, Andrea A. Vilela1, Rodrigo B. M. Barretto2, Elizabete S. Santos1, Amanda G. M. R. Sousa1, Ari Timerman1 (1) Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil; (2) Instituto do Coracao (INCOR), University of Sao Paulo, Brazil; (3) D'Or Institute for Research and Education (IDOR), Hospital Alianca, Salvador, Brazil; (4) Grupo Paulo; (5) Bahiana School of Medicine and Public Health, Salvador, Brazil. Background: Cardiovascular disease is the leading cause of death in Brazil and worldwide. In the context of diastolic dysfunction, echocardiography is the best non-invasive diagnostic method. However, the comparison of the two main guidelines for evaluate left ventricular diastolic function in acute coronary syndrome (ACS) is scarce. Objective: To compare the prognostic value of both guidelines of American Society of Echocardiography, from 2009 and 2016, in patients with ACS. Methods: This is a sub-analysis of a prospective cohort observational study with 109 patients admitted to the emergency with ACS. The follow up was performed within 1 year and combined outcome was cardiovascular death or new heart failure. We used the non-parametric Spearman method to assess the correlation between the categories of diastolic function according to the guideline used. The Cox model and the Log rank test with Kaplan-Meier curves were used to compare the prognostic value of categorizing patients according to the guideline used. The results were expressed as hazard ratio with a confidence interval of 95%. Results: The mean age was 63 years +-11, most male patients (73.4%) and the predominant color of patients was white (60.4%). Among the main risk factors, the most frequent for coronary artery disease was dyslipidemia (78%), followed by systemic arterial hypertension (77.1%) and sedentary lifestyle (65.9%). The study identified a mean borderline ejection fraction, a high E/E' ratio, and LV diastolic and systolic volumes presented means above normal. The most common electrocardiographic change on admission was T-wave inversion (45%), and NSTEMI was the main clinical diagnosis (74%). The categories in which there was a greater disagreement between the guidelines were grade II diastolic dysfunction and normal function. The correlation between the diagnosis of diastolic dysfunction when compared to the use of the 2009 and 2016 guidelines was weak (R = 0.56 by Spearman's method; p < 0.001). By the Kaplan-Meier curves, dividing the groups into with or without LA pressure elevation, the distinction between the evolution of the two groups is significant when performed by the 2016 guideline (Log Rank = 8.17; p = 0.04). Conclusion: The current guideline (2016) for the assessment of left ventricular diastolic dysfunction showed a higher prognostic value of combined outcome of cardiovascular death or new heart failure within one year, when compared to the guideline of 2009 in patients. 111722 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Artificial Intelligence Technology-Based Capnography Waveform Processing and the Presence of Heart or Pulmonary Disease in Hospitalized Individuals ALEXANDRA CORREA GERVAZONI BALBUENA DE LIMA1, Caroline Barreto Cavalcanti1, Paula Fernandes Freitas Lima1, Barbara Cunha Barreto2, Bruno Ramos Carneiro2, Gabriela de Oliveira Silva2, Maria Alice Ramalho Bragatto2, Ilan Sousa Figueiredo3, Wenisten Jose Dantas da Silva3, Erick Giovani Sperandio Nascimento3, Luis Moreira da Silva de Azevedo Meireles4, Sergio Henrique Rodolpho Ramalho5 (1) North Wing Regional Hospital - Brasilia - Brazil; (2) School of Health Sciences - Brasilia - Brazil; (3) Manufacturing and Technology Integrated - Campus SENAI CIMATEC, Salvador, Bahia, Brazil; (4) MDI Industrial, Salvador, Bahia - Brazil; (5) Coordinator of the Clinical Research Center of the Brasilia of the Dasa Hospitals Network - Brasilia - Brazil Background: Dyspnea is challenge in hospitalized individuals. The reasons for dyspnea are often multifactorial and the evaluation may use different and expensive methods (ex.: arterial blood gas, natriuretic peptide measurement, echocardiogram, computed tomography). This objective of this study was to assess the accuracy of an artificial intelligence (AI) capnography waverform and the presence of heart or pulmonary disease using the AI technology. Methods: In this prospective observational study, of patients admitted to a public hospital in Brasilia, Brazil, from September 2021 to February 2022, deep learning algorithms were developed and validated using capnography waveforms acquired from patient monitoring. The classification model was a binary classifier of individuals with healthy patients and sick patients (heart disease or pulmonary disease or heart and pulmonary disease) by analyzing biosignal waveforms. We assessed the model performance using area under the receiver operating characteristic curve (AUC-ROC), Accuracy, Sensitivity, Recall, F1-score, and Specificity. Results: Among them, 286 cases were taken as the experimental group, 61 (21%) heart disease, 69 (24%) pulmonary disease, 85 (30%) heart and pulmonary disease and 71 (25%) without heart or pulmonary disease (healthy patients). The AI model revealed a true positive (sick patients) of 88% and a true negative (healthy patients) of 82%. Therefore, the AI capnography waveform algorithm showed an average performance of 86% of Accuracy, 85% of Specificity, 85% of Recall and 83% of Precision, 84% of F1-score, and 85% of AUC-ROC. Conclusions: Capnography is a non-invasive, low-cost, and easy-to-use equipment. The capnography waveform could predict the presence or absence of heart or pulmonary disease based on biosignals acquired using noninvasive patient monitoring. The research showed that the design of AI information processing can assistant the clinical diagnostic and evaluation of patients. 111727 Modality: E-Poster Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Immediate and Long-Term Predictor Score of Success After Percutaneous Mitral Balloon Commissurotomy RAFAEL ALEXANDRE MENEGUZ MORENO1, Luiz Eugenio B. Prota-Filho1, Caio C.V. Queiroz1, Fabricio C. Wohnrath1, Felipe A.C. Carboni1, Gisele R.C. Silva1, Joselyn I.P. Castro1, Wandemberg S. Silva1, Auristela I.O. Ramos1, Nisia L. Gomes1, Sergio L.N. Braga1, J. Ribamar Costa Jr1 (1) Instituto Dante Pazzanese de Cardiologia Background: Percutaneous mitral balloon commissurotomy (PMBC) remains the preferred treatment for patients with severe symptomatic rheumatic mitral stenosis (MS) and suitable anatomy. The objective of this study was to propose a new score for the prediction of immediate and late success. Methods: This is a retrospective, single-center, single-arm registry encompassing all 1915 consecutive patients with rheumatic mitral stenosis recruited and referred to PMBC between August 3rd 1987 and July 19th 2010. All data were previously collected and recorded in a dataset. Clinical status was determined according to the New York Heart Association (NYHA) classification. Long-term outcome was a composite of incidence of major adverse cardiac events (cardiovascular death, new PMBC or mitral valve repair surgery) up to 24 years of clinical follow-up (from 1988 until December 3rd, 2011), including cardiovascular death, need for new PMBC, or mitral valve replacement surgery. Results: Mean patient age was 36.8 +- 12.9 years, most (86.4%) were female, and Wilkins score was between 9-11 in 49.1% of patients. In the multivariate analysis, the predictors of immediate success were age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; p = 0.01), left atrium size (OR, 0.96; 95% CI, 0.93-0.99; p = 0.01), mean pre-procedure mitral gradient (OR, 0.93; 95% CI, 0.89-0.96; p < 0.001), intermediate Wilkins score 9-11 (OR, 0.62; 95% CI, 0.40-0.94; p = 0.02), and high Wilkins score >=12 (OR, 0.35; 95% CI, 0.16-0.76; p < 0.01). For prediction of late events, age (hazard ratio [HR], 0.98; 95% CI, 0.97-0.98; p < 0.001), New York Heart Association class III-IV (HR, 1.50; 95% CI, 1.18-1.92; p < 0.001), left atrium size (HR, 1.02; 95% CI, 1.02-0.04; p < 0.01), and high Wilkins score >=12 (HR, 2.02; 95% CI, 1.30-3.15; p < 0.01) were significant. Two nomograms were developed using significant predictors from the model (one for immediate results and another for long-term results). Conclusions: In this large population, not only the Wilkins score, but also clinical and hemodynamic features, seem to be relevant in predicting immediate and late success for patients with rheumatic MS who underwent PMBC. 111724 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Impact of Rapid Titration of Beta Blockers on Functional Capacity in Patients with Advanced Heart Failure and Analyzed Through the 6-Minute Walk Test DOMINGOS SAVIO BARBOSA DE MELO2, Domingos Savio Barbosa de Melo2, Antonio Carlos Pereira Barreto1, Aristea Izabel de Oliveira2, Rodrigo Savio de Oliveira Melo2, Breno Domingos de Gusmao Melo2 (1) Heart -FMUSP; (2) Ergocardio Medicina Diagnosis and Research Background: Rapid up-titration of beta-blockers (BB) in the treatment of heart failure (HF) during hospitalization has yet to be tested. Objectives: The purpose of this research was to evaluate the correlation between the rapid up-titration of beta-blockers and functional capacity in patients hospitalized for HF using the 6-minute walk test (6MWT) as a parameter. Methods and Results: 92 patients with advanced HF (New York Heart Association [NYHA] IV) and left ventricle ejection fraction (LVEF) <45% were hospitalized for clinical compensation and followed-up for one year after discharge. The patients were distributed into two groups: 46 in the treatment group (TG) and 46 in the control group (CG). During hospitalization, they were divided randomly for BB rapid up-titration with an increase of dosage every two days (TG), or by the usual treatment regime (CG). Statistical analysis used: Student's t-test, Mann-Whitney, Chi-square and Fisher's exact test, Kaplan-Meier for survival, using the Log-rank test for comparison and the hazard ratio (HR) calculated with the Cox model. P < 0.05 was considered significant. The exercise tolerance analysis was performed at the entrance, three months and one-year intervals and the walking distance was stratified into four levels (NV): NV1 <300 meters (m), NV2 = 300-375 m, NV3 = 375-450 m and NV4 > 450 m. At the entrance moments, three months and one year the distance traveled for the TG/CG were, respectively, 206.62 +- 33.54/185.09 +- 32.32 meters, 384.55 +- 77.54/336.55 +- 65.23 meters, and 422.17 +- 98.57/387.41 +- 76.66 meters. It was verified that there was an increase in walking distance for the two groups studied (p = 0.002). However, the distance walked in the TG was significantly higher than in the CG (p < 0.001). Conclusions: The rapid up-titration of beta blockers dosage during hospitalization of end-stage HF patients compared to the usual treatment regimen in advanced HF is safe, effective, and promotes increased functional capacity through 6MWT analysis. 111743 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Evaluating the Trial Strategy for Dosage Application of Beta-Blockers and Their Impact on the Quality of Life using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) DOMINGOS SAVIO BARBOSA DE MELO2, Antonio Carlos Pereira Barretto1, Aristea Izabel de Oliveira2, Rodrigo Savio de Oliveira Melo2, Breno Domingos de Gusmao Melo2, Domingos Savio Barbosa de Melo2 (1) Heart -FMUSP; (2) Ergocardio Medicina Diagnosis and Research Background: Rapid up-titration of beta-blockers (BB) in the treatment of heart failure (HF) during hospitalization has yet to be tested. Objectives: Our purpose for this research is a new model for administering beta-blockers in patients with end-stage HF in order to, after clinical compensation of the patient, promote more rapid dosage increments than the conventional method or usual care procedures. We also sought to ascertain whether or not this model for administering beta-blockers could modify the impact of HF in relation to the enhancement of the quality of life (QOL) as measured by the Minnesota Living with Heart Failure questionnaire. Methods and Results: 92 patients with advanced HF (New York Heart Association [NYHA] IV) and left ventricle ejection fraction (LVEF) <45% were hospitalized for clinical compensation and followed-up for one year after discharge. The patients were distributed into two groups: 46 in the treatment group (TG) and 46 in the control group (CG). During hospitalization, they were divided randomly for BB rapid up-titration with an increase of dosage every two days (TG), or by the usual treatment regime (CG). Statistical analysis used: Student's t-test, Mann-Whitney, Chi-square and Fisher's exact test, Kaplan-Meier for survival, using the Log-rank test for comparison and the hazard ratio (HR) calculated with the Cox model. P < 0.05 was considered significant. The pcts responded to the questions of the MLHFQ. This battery of 21 items uses a scale for answers from (0-5). Total compilation of scores varied from 0 to 105. A lower score reflects a better QOL. Among the total group of 92 patients studied, initially, LVEF average was 27.02%, end-diastolic diameter average was 66.15 mm, and end-systolic diameter average was 57.04 mm. For the TG, the average dosage of Carvedilol reached 34.37 mg/per day; and with the CG, 13.99 mg/per day. In the initial evaluation, the pcts showed an average score of 82 points in the two separate groups evaluated. With treatment, the TG moved to a score of 63, while the CG scored 73. There was a reduction of 23% in the MLHFQ score for the TG in relation to the CG group (p < 0,001). Conclusions: Beta blockers rapid optimization dosages during hospitalization of end-stage HF patients is safe and promotes an enhanced patterns of QOL as measured by MLHFQ, indicating that more elevated dosages of BB is probably responsible for this positive outcome than that observed with a usual treatment schedule. 111747 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Value of Ventricular Premature Beats and Non-Sustained Ventricular Tachycardia in Predicting the Presence of Myocardial Fibrosis in Chronic Chagas Cardiomyopathy ANDRE SCHMIDT1, Maria Fernanda Braggion-Santos1, Marcel Koenigham Santos1, Gustavo Jardim Volpe1, Henrique Turin Moreira1, Jose Antonio Marin-Neto1 (1) Faculdade de Medicina de Ribeirao Preto - USP Introduction: Myocardial fibrosis (MF) identified in Cardiac Magnetic Resonance (CMR) is a recognized prognostic marker in Chronic Chagas Cardiomyopathy (CCC). Since CMR is not widely available, it seems relevant to identify markers of MF in other methods that may indicate the need for a CMR in this neglected disease. Objective: We sought to investigate the relationships between the presence of ventricular premature beats (VPB) in an Electrocardiogram (ECG), Non-sustained ventricular tachycardia (NSVT) on a Holter exam, and the presence of MF at CMR. Methods: Consecutive CCC patients with an ECG, Holter, and CMR within one year were selected from our institution database, and the presence of VPB on ECG, NSVT on Holter, and MF on CMR were collected, as well as demographic and clinical data. Descriptive statistics, Fisher exact tests, and logistic regression analysis were performed. A 5% level of significance was established. Results: Inclusion criteria were fulfilled by 121 patients, 53% females, 56 +- 14 years, and most (93%) were in NYHA class I or II. The mean left ventricular ejection fraction was 48 +- 14%. Amiodarone was used by 22 (18%) patients at the physician's discretion. Twenty-three (19%) patients resting ECG presented VPBs, and 38 (31%) patients had NSVT on Holter. MF was identified in 94 (78%) CCC patients. Concomitant occurrence of VPBs on ECG and NSVT on Holter in the same patient was low (12%) but MF was present in all of those with both VPB and NSVT. VPBs in ECG indicated an odds ratio (OR) of 7.9 (CI: 1.02-61.9; P = 0.04) of having MF, as 22 (96%) out of 23 with VPB had it. NSVT on Holter presented an OR of 16.9 (CI: 2.2-129.8; p = 0.007) as 37 (97%) out of 38 patients with NSVT had MF on CMR. Amiodarone use did not significantly (p > 0.05) influence the results of each exam to predict MF. Conclusions: Electrocardiogram and Holter may present findings indicating MF occurrence in CCC. Although rare in resting ECGs, VPB significantly increases the odds of finding MF. The presence of NSVT has a much higher chance of finding MF in a CMR exam. These findings may indicate a subgroup of CCC patients that should be followed closely due to the possible presence of myocardial fibrosis. 111933 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Evaluation of Overtraining Syndrome in Patients from a Cardiac Rehabilitation Program ALTAIR ARGENTINO PEREIRA JUNIOR1, Ana Ines Gonzales2, Darlene Aparecida Pena1, Tales de Carvalho3, Alexandro Andrade3, Sabrina Weiss Sties1 (1) Centro Universitario Avantis - UNIAVAN; (2) Centro Universitario para o desenvolvimento do Alto Vale do Itajai - UNIDAVI; (3) Universidade do estado de Santa Catarina - UDESC Introduction: In the context of cardiac rehabilitaion, the practice of regular physical exercises is considered a mandatory therapeutic strategy, since it significantly reduces the morbidity and mortality of patients with heart disease. However, especially in individuals with low exercise tolerance, the overtraining syndrome could occur. Objective: Evaluate the presence of signs of overtraining syndrome in patients with coronary artery disease undergoing cardiac rehabilitation. Methods: Seventy-seven adults participated in the cardiac rehabilitation program were analized. For early detection of overtraining syndrome was used the Brunel Mood Scale. Data were evaluated by descriptive statistics. Results: In this study, the prevalence of overtraining syndrome among patients with coronary artery disease was 11.68%. The tension domain score was 4.44 (+-3.25), depression 4.22 (+-3.07), anger 0.78 (+-1.09), fatigue 4.89 (+-3.52) and mental confusion 3.33 (+-2.87) were high, while the vigor domain (9.67 +- 3.24) was low, indicating signs of overtraining syndrome. Conclusion: Some patients with coronary artery disease showed signs of overtraining syndrome. Taken together, these results indicate this target population requires attention to the need for adopt strategies aiming at preventive measures. 111935 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Left Atrial Minimum Volume is Better Correlate of Left Atrial Dysfunction by Two-Dimensional Strain RAFAEL MODESTO FERNANDES3, Rafael Modesto Fernandes3, Andre Moises de Oliveira Nunes5, Hayala Machado Cavalcante Conceicao5, Loren Lacerda Rodrigues5, David Le Bihan4, Andrea A. Vilela1, Rodrigo B. M. Barretto2, Elizabete S. Santos1, Amanda G. M. R. Sousa1, Ari Timerman1 (1) Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil; (2) Instituto do Coracao (INCOR), University of Sao Paulo, Brazil; (3) D'Or Institute for Research and Education (IDOR), Hospital Alianca, Salvador, Brazil; (4) Grupo Fleury - Sao Paulo; (5) Bahiana School of Medicine and Public Health, Salvador, Brazil. Background: The analysis of left atrial (LA) function can add important information to the understanding of cardiovascular diseases. Therefore, to assess its functioning the use of volumetric measurements is adopted. The maximum LA volume is the most echocardiography parameter used, however, some studies demonstrated that minimum LA volume is better to correlate with atrial dysfunction. Purpose: The purpose of this study was compare the accuracy of the phasic volumes of the left atrium in determining LA dysfunction identified by the two-dimensional strain. Methods: This observational, cross-sectional study admitted 109 participants with diagnosis of acute coronary syndrome non-ST-segment elevation. The exams were performed within 72 hours of admission. LA volume was defined by the mean of measurements performed in the four and two-chamber apical windows using Simpson's method. The phasic volumes of the left atrium were measured using an electrocardiogram synchronized with the device. Reservoir LA strain less than 21% was the cut off to LA dysfunction. Results: The phasic LA volume variables analyzed were maximal (LAVMAX), minimal (LAVMIN) and before atrial contraction (LAVBAC) volume, and each variable indexed for body surface (LAVIMAX, LAVIMIN and LAVIBAC). Therefore, a Roc curve was generated for each volume variable to assess which would be more accurate in predicting left atrial dysfunction. The Youden index was used to determine the cutoff point for each one of them. The areas under the Roc curves were: 0.83 (LAVIMIN), 0.81 (LAVMIN), 0.78 (LAVBAC), 0.76 (LAVIMAX), 0.74 (LAVIBAC) and 0.71 (LAVMAX). Conclusion: This study concluded that phasic volumes were good determinants of left atrial dysfunction identified by 2D strain. The minimum left atrial volume was the better correlated with left atrial dysfunction. 111782 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Clinical and Angiographic Predictors of Troponin Elevation After Non-Complicated Angioplasty: A Cross-Sectional Study INGRID LOUREIRO DE QUEIROZ LIMA1, THIAGO CAVALCANTE1, LUIZ CARLOS DE LIMA1, FERNANDO LUIZ WESTPHAL1 (1) UNIVERSIDADE FEDERAL DO AMAZONAS; (2) HOSPITAL DO CORACAO FRANCISCA MENDES Background: Troponin T (TnT) and troponin I (TnI) are myocardium necrosis biomarkers very sensible and specific used to evaluate a myocardial injury, and their rise after coronary angioplasty correlate with worst prognoses. Complications associated with this procedure are a well-recognized cause of elevated myocardial necrosis biomarkers. In its absence, the exact causes of elevated troponin are merely speculative. Objective: To evaluate the relationship between troponin elevation and clinical and anatomical variables after coronary angioplasty in the absence of complications. Method: It is an epidemiological study evaluating 124 patients submitted to coronary angioplasty from December 2018 to December 2019 in the catheter laboratory of University Hospital Francisca Mendes, using clinical variables and troponin doses before, 6 hours and 12 hours after the procedure. Results: Of all 124 analyzed patients, 63,3% were male and mean age of 63 years old. The mean implanted stents per patients was 1,66. Hypertension was the most prevalent comorbidity. Eighty patients (64,5%) presented high troponin dosage (compared to 99th percentile) and 32 (25,8%) showed troponin dosage above five times the 99th percentile. When analyzing all patients presenting troponin dosage above 99th percentile, none of the clinical characteristics were significantly related to troponin alteration. While analyzing procedure-related characteristics, we observed that troponin elevation above 99th percentile is significantly correlate with the number of implanted stents, the number of treated arteries (p < 0,001 and p = 0,046 respectively), procedure duration (p = 0,032), and contrast media volume (p = 0,008). The number of implanted stents and number of treated arteries were still associated with troponin elevation above five times the 99th percentile. Conclusion: Clinical characteristics were not associated with troponin elevation above the 99th percentile. However, the procedure duration, contrast media volume, number of treated arteries, and number of stents implanted are significantly associated with troponin elevation when studying the procedure characteristics. Amongst the subgroup of patients with troponin levels above five times the percentile, clinical history of smoking, the number of implanted stents and stent length were significantly associated with the elevation of this biomarker above five times the 99th percentile. 111805 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Predictors of Mortality in Cardiac Valve Surgery - a Prospective Cohort GABRIEL ASSIS LOPES DO CARMO1, Barbara Carolina Silva Almeida1, Gabriela Zamunaro Lopes Ruiz1, Renato Braulio1, Ana Cristina Carioca1, Fabio Morato Castilho1, Claudio Leo Gelape1, Bruno Rodrigues Pereira1, Luiza Moreira Gomes1, Ana Carolina Sudario Leite1 (1) Universidade Federal de Minas Gerais (UFMG) Introduction: Rheumatic valve disease (RVD) has a high prevalence in Brazil, but remain poorly studied. Different from developed countries, valvar cardiac surgeries are the most performed procedure in several public hospitals in Brazil. However, impact of RVD on cardiac surgery is not well established. Objective: Describe baseline characteristics and prognosis of cardiac valve surgery patients in a public hospital in Brazil. Methodology: Prospective cohort analysis of cardiac surgery patients between 2016 and 2021, excluding heart transplant. Results: We enrolled 416 patients in the study, median age 57 (47;67) and 377 (49,8%) females. Overall, 287 (69,2%) procedures were elective, while 115 (27,7%) were urgent and 13 (3,1%) emergencies. Most procedures, 330 (79,3%), were isolated valve surgery, followed by combined valve and coronary artery bypass surgery (CABG), 36 (8,6%), valve and aorta, 19 (4,6%), valve and congenital, 8 (1,9%), valve, CABG and aorta, 2 (0,5%), and valve plus other cardiac surgery in 21 (5,1%). 147 (23,3%) had previous cardiac surgery. Diabetes was present in 69 (16,6%), 47 (11,3%) non-insulin dependent and 22 (5,3) insulin dependent. 25 (6%) had a history of previous myocardial infarction, 40 (9,6%) had stroke, 21 (5%) chronic pulmonary disease, 141 (43,9%) atrial fibrillation, 143 (44%) had rheumatic valve disease and 8 (1,9%) were on renal replacement therapy. Heart failure was diagnosed in 303 (73,5%) and 50 (12,1%) had a NYHA IV classification. Median ejection fraction was 63% (55;68), PSAP was 42 (31;55) and creatinine 0,98 (0,8;1,15). Observed in-hospital mortality was 13,0%. Univariate analysis showed that age, 67 (56;74) vs 56 (46;66), p = 0,002, endocarditis, 14 (30,4%) vs 40 (10,8%), OR = 3,60 (1,77-7,31), p < 0,001, mitral replacement plus tricuspid repair, 18 (23,4%) vs 26 (11,6%), OR = 2,34 (1,18-4,63), p = 0,013, and non-elective procedures, 27 (21,1%) vs 27 (9,4%), OR = 2,57 (1,44-4,60), p = 0,001 were related to increased mortality. Rheumatic etiology was a protective factor, 17 (9,3%) vs 37 (15,9%), OR = 0,54 (0,29-0,99), p = 0,045. In multivariate analysis, only age, OR = 1,058 (1,025-1,091), p = 0,001, endocarditis, OR = 4,51 (1,717-11,855), p = 0,002, and mitral replacement plus tricuspid repair, OR = 2,903 (1,325-6,362), p = 0,008, remained statistically relevant. Conclusion: Our study shows that older age, endocarditis and mitral replacement combined with tricuspid repair are associated with increased mortality after cardiac valve surgery. 111816 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Implementation of Telecardiology Service and ST-Elevation Myocardial Infarction in the State of Sergipe, Brazil: A Pilot Study JOSE EDIVALDO DOS SANTOS1, Jose Victor Furtado Jaco de Oliveira2, Maria Leticia de Franca Oliveira2, Rafael Alexandre Meneguz-Moreno2 (1) Hospital de Urgencias de Sergipe; (2) Universidade Federal de Sergipe - Campus Lagarto Introduction: The implementation of Telecardiology (TCL) in the state of Sergipe, Brazil, is a viable, promising and innovative strategy. Regarding specifically STEMI (ST-elevation myocardial infarction), it is known that mortality is directly proportional to the first medical contact to balloon time. The objective of the study is to evaluate data regarding patients with STEMI regulated by TCL service in Sergipe and referred to a tertiary hospital. Methods: This is a cross-sectional, retrospective, descriptive study, reporting data from June 2021 to April 2022 involving TCL service. Data were collected from electronic medical records, through the e-SUS program. Results: The resulting analysis population included 444 patients presented with STEMI during 11 months, being 288 (65%) male, mean age 61 years old, ranging from 27 to 102 years. Patient had previous hypertension (55%), diabetes mellitus type 2 (32%), dyslipidemia (12,8%), smoking (12,8%), previous coronary artery disease (5,6%), obesity (4,0%) and 68 (15,3%) reported no comorbidities. From all patients presented with STEMI during the analyzed period, 294 (66,2%) patients were referred to immediate PCI (percutaneous coronary intervention), 51 (11,4%) had been submitted to thrombolytic (TB) therapy, and 99 (22,2%) were not treated with reperfusion therapy within 12 hours of symptoms onset, yet 47 (47,4%) from these 99 patients were referred to urgent coronary angiography after TCL cardiologists evaluation. Among TB group, 32 (62,7%) patients were referred to a CICU (Coronary Intensive Care Unit) immediately after reperfusion, 2 (4%) were referred to rescue PCI and 17 (33,3%) have not been transported. The reasons for choosing TB therapy were, as follows, long distance (21), no transport available (6), no CICU vacancy (6), choice of attending physician (5) and not informed (13). There were 22 (5%) deaths among all patients, 4 from PCI group, 4 from TB group and 14 from the other group. Conclusion: At the beginning of TCL service in Sergipe, there were some patients that still have no access to PCI. However, with the consolidation of TCL, this flowchart was reorganized and since October 2021, there was no lack of vacancy. Therefore, TCL has improved the quality of STEMI care in the state of Sergipe (northeast Brazil). Strategies must still be implemented to increase PCI rates, such as improvement on medical education, in order to recognize symptom and trigger the TCL service more quickly. 111830 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Clinical Characteristics and Prognosis of Cardiac Surgery Patients in a Public Hospital in Brazil GABRIEL ASSIS LOPES DO CARMO1, Barbara Carolina Silva Almeida1, Gabriela Zamunaro Lopes Ruiz1, Renato Braulio1, Ana Cristina Carioca1, Fabio Morato Castilho1, Claudio Leo Gelape1, Bruno Rodrigues Pereira1, Luiza Moreira Gomes1, Ana Carolina Sudario Leite1 (1) Universidade Federal de Minas Gerais (UFMG) Introduction: Knowing baseline clinical information is important to compare results between different institutions. Brazil has a particular socioeconomic scenario and disease profile that make users of public health system (SUS) unique. Objective: Describe baseline characteristics and prognosis of cardiac surgery patients in a public hospital in Brazil. Methodology: Prospective cohort analysis of cardiac surgery patients between 2016 and 2021, excluding heart transplant. Results: We enrolled 633 patients, median age 58 (48;67) and 377 (49,8%) females. Most procedures, 406 (64,1%), were elective, followed by urgent, 109 (31,4%), and emergent, 28 (4,4%). Most surgeries were valvar, 416 (65,5%) followed by coronary artery bypass surgery (CABG), 188 (29,6%), aorta, 43 (6,8%), congenital heart disease, 33 (5,2%), and other surgeries, 50 (7,9%). 147 (23,3%) had previous cardiac surgery. Diabetes was present in 133 (20,9%), 88 (13,9%) non-insulin and 45 (7,1) insulin dependent, myocardial infarction in 76 (12%), stroke in 59 (9,3), chronic pulmonary disease in 29 (4,6%), atrial fibrillation in 150 (23,6%), rheumatic valve disease in 134 (21,1%) and 13 (2%) were on renal replacement therapy. Heart failure was diagnosed in 370 (58,9%) and 56 (8,8%) had a NYHA IV classification. Median ejection fraction was 62% (54;68), PSAP was 38 (29;51) and creatinine, 0,97 (0,8;1,18). Mean and median EUROSCORE II were 3,978 (+-6,591) and 1,8 (0,990;4,020), respectively. Observed in-hospital mortality was 13,3%. Conclusion: Our results show a much higher than predicted mortality according to EUROSCORE II. However, our population has some important differences from that evaluated in EUROSCORE II study, especially a higher prevalence of rheumatic valve disease. Also, more commonly patients were operated on an urgent basis. Our population had more similarities with the InsCor Risk Assessment study performed in Brazil, which found a general mortality of 8,9%, but included only CABG and valve surgeries. Due to these specific baseline characteristics, local developed score would be more appropriate while evaluating cardiac surgery candidates in Brazil. 111860 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Cardiopulmonary Exercise Test Variables and its Association with Quality of Life in Patients with Chronic Chagas Cardiomyopathy: Results from the Peach Study MARCELO CARVALHO VIEIRA1, Fernanda de Souza Nogueira Sardinha Mendes1, Paula Simplicio da Silva1, Gilberto Marcelo Sperandio da Silva1, Flavia Mazzoli-Rocha1, Andrea Silvestre de Sousa1, Roberto Magalhaes Saraiva1, Vitor Barreto Paravidino2, Luiz Fernando Rodrigues Junior3, Alejandro Marcel Hasslocher-Moreno1, Pedro Emmanuel Alvarenga Americano do Brasil1, Mauro Felippe Felix Mediano1 (1) Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.; (2) Institute of Social Medicine, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; (3) Department of Research and Education, National Institute of Cardiology, Rio de Janeiro, RJ, Brazil Introduction: The association between functional capacity and quality of life (QoL) in individuals with chronic Chagas cardiomyopathy (CCC) is still poorly investigated, with the few studies including indirect measures of functional capacity, limiting the validity and the interpretation of the results. Objective: The present study aimed to evaluate the association between functional capacity (quantified by cardiopulmonary exercise test [CPET]) and QoL in individuals with CCC. Methods: A cross-sectional analysis using baseline data from PEACH study, a randomized clinical trial that evaluated the effects of exercise training in patients with CCC, was performed. QoL was assessed using the SF-36 questionnaire. Sociodemographic, anthropometric, clinical, cardiac function and maximal progressive CPET variables were retrieved from PEACH study dataset. Generalized linear models adjusted for age, sex, and left ventricular ejection fraction were performed to evaluate the association between CPET variables and QoL. Results: After adjustments for potential confounders, VO2peak and VO2AT were both positively associated with physical functioning and physical component summary (PCS). Double product was positively associated with physical functioning, general health perceptions, and PCS, whilst heart rate recovery <12bpm at the first minute (HRR) was negatively associated with physical functioning, role limitations due to physical problems, bodily pain, and PCS. VE/VCO2 slope presented a negative association with all mental scales of SF-36: vitality, social functioning, role limitations due to emotional problems, mental health, and mental component summary. HRR <12bpm was negatively associated with vitality and mental health. Double product was positively associated with vitality. The CPET variables that most explained the QoL variation in the adjusted models were VO2AT (50% for physical functioning and 36% for PCS), VO2peak (31% for physical functioning and 21% for PCS), VE/VCO2 slope (45% for mental health and 31% for mental component summary), and HRR < 12 bpm (20% for vitality). Conclusions: The association between CPET variables and QoL reinforces the importance of CPET inclusion for a more comprehensive evaluation of individuals with CCC. Intervention strategies aiming to improve functional capacity may also promote additional benefits on QoL and should be incorporated as a treatment strategy for patients with CCC. 111901 Modality: E-Poster Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Exercise Training on Quality of Life in Patients with Chronic Chagas Cardiomyopathy: From the Peach Study MARCELO CARVALHO VIEIRA1, Fernanda de Souza Nogueira Sardinha Mendes1, Paula Simplicio da Silva1, Gilberto Marcelo Sperandio da Silva1, Flavia Mazzoli-Rocha1, Andrea Silvestre de Sousa1, Roberto Magalhaes Saraiva1, Fernanda Martins Carneiro1, Luiz Fernando Rodrigues Junior2, Alejandro Marcel Hasslocher-Moreno1, Pedro Emmanuel Alvarenga Americano do Brasil1, Mauro Felippe Felix Mediano1 (1) Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.; (2) Department of Research and Education, National Institute of Cardiology, Rio de Janeiro, RJ, Brazil Introduction: Physical exercise has been described as an efficient and safe strategy to improve quality of life (QoL) in heart failure (HF). However, there is a lack of information about its influence on the QoL of patients with chronic Chagas cardiomyopathy (CCC). Objective: The present study aimed to investigate the effect of physical exercise training on the QoL of patients with CCC. Methods: PEACH study was a single center, superiority randomized parallel-group clinical trial of exercise training versus a control group with no exercise training. The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction <45% or HF symptoms (CCC stages B2 or C). QoL was assessed at baseline, after three months, and at the end of follow-up (six months) using SF-36 questionnaire. Patients randomized for the intervention group performed physical exercise (aerobic exercise, strength training and stretching exercises) for 60 minutes, three times a week, for a period of six months. Patients in the control group were not provided with a formal exercise prescription. During the study, patients from both groups underwent monthly appointments with the same cardiologist, and with other specialists, if necessary. In addition, patients in both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of physical training on QoL, considering the interaction term (group x time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using mixed linear models. Analyses were adjusted to the baseline QoL values. Results: There were significant improvements in physical functioning (b = +10.7; p = 0.02), role limitations due to physical problems (b = +25.0; p = 0.01) and social functioning (b = +19.2; p < 0.01) scales during the first three months in the exercise group compared to control group. No significant differences were observed between groups after six months of follow-up. Conclusion: Exercise training was associated with short-term improvements in physical and social aspects of QoL and should be incorporated as a treatment strategy for patients with CCC. 111898 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Hypertrophic Cardiomyopathy Carriers Characteristics in a Cardiogenetics Investigation Service BRAULIO CRUZ MELO1, Larissa Rebeca da Silva Tavares1, Irlaneide da Silva Tavares3, Antonio Guilherme Cunha de Almeida1, Antonio Carlos Sobral Sousa2, Joao Vitor Andrade Pimentel2, Emerson de Santana Santos2, Enaldo Vieira de Melo2, Giovanna Medeiros Resende1, Evelen Rouse de Souza Santos1, Diego Henrique da Silva Tavares1, Joselina Luzia Menezes Oliveira2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe; (3) Hospital Primavera Introduction: Hypertrophic Cardiomyopathy (CMH) is the most common genetic disease in the world, and can lead their carriers to death, therefore making it's correct diagnosis fundamental, along with the follow-up and genetic counseling of patients and their family. Methods: This is a cross-sectional, prospective and analytical study, with patients diagnosed with CMH in Sergipe between January 2021 and April 2022, being also subjected to genetic study. Objective: To describe the patient population under CMH investigation. Results: 80 patients were studied, 49 (61%) being of male gender, with the average age of 49. MRI was performed in 50 patients and positive for CMH in 45 (90%); 71 patients have resting echocardiogram, 60 of which cover CMH criteria. The most relevant echocardiographic variant for CMH is septal thickness, with an average of 15,5 mm on echocardiogram and 16,5 on MRI. It's obstructive form was present at the MRI in 20% of the cases (10 patients), ischemia in 18 (39% in the septal wall), and fibrosis in 40 patients (80%). The doppler echocardiogram under physiological stress was performed in 21 patients, 11 on the treadmill, 2 on the bicycle and 6 on both methods which made possible the identification of 7 individuals with labile obstructive form. Finally, in the genetic study, the most found genes were MYBPC3 and MYH7 (28 and 12%, respectively), in agreement with whats already described in literature, in addition to 30% of cases being identified as phenocopies. Conclusion: The CMH can appear more frequently than expected and present variable expressiveness and penetration. Ocasionally, phenocopies and dislead it's diagnosis. The echocardiographic evaluation under physiological stress can identify higher risk individuals (labile obstructive CMH). 111910 Modality: E-Poster Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Electrocardiographic Abnormalities in Chronic Chagas Cardiomyopathy and its Correlation with Presence and Burden of Myocardial Fibrosis and Left Ventricular Ejection Fraction Measured by Cardiac Magnetic Resonance ANDRE SCHMIDT1, Maria Fernanda Braggion-Santos1, Marcel Koenigkam Santos1, Gustavo Jardim Volpe1, Henrique Turin Moreira1, Jose Antonio Marin-Neto1 (1) Faculdade de Medicina de Ribeirao Preto - USP Background: Chronic Chagas' cardiomyopathy (CCC) is a consequence of several insults resulting in myocardial fibrosis (MF). Detection of MF is possible noninvasively through cardiac magnetic resonance (CMR). However, it is an expensive and not widely available method. Objective: This study aims to correlate ECG Selvester score (or QRS score) with quantification of MF and left ventricular ejection fraction (LVEF) through CMR analysis, in patients with CCC. Methods: Retrospective analysis of ECG and CMR exams, performed within one year of 194 patients with CCC. Rassi score was evaluated in 171 patients. Continuous variables were presented as median and interquartile range (IQR)and categorical data were summarized as percentages. Spearman's rank correlation coefficient was used to evaluate the correlation between estimated MF by QRS score and quantified MF by CMR, and LVEF. Bland-Altman plot was applied to compare percentage of MF estimated by QRS score and measured by CMR. Patients were divided into tertiles based on QRS score values and Kruskal-Wallis test was applied to compare MF and LVEF among the groups. Receiver Operating Characteristic curves (ROCcurve) were generated to define cut-off values with the best accuracy to identify MF >= 10% of left ventricular mass, MF >= 12.3 g, LVEF < 50%, or LVEF < 35%. According to Rassi score classification, patients were separated in 3 risk groups, and QRS scores were evaluated by the Kruskal-Wallis test. P < 0.05 was considered statistically significant. Results: A total of 98 participants were women. Median age was 56 years(IQR: 44-67). Correlation between QRS score and MF by CMR was moderate (r = 0.45,p < 0.001), as well as the negative correlation between QRS score and LVEF (r = -0.42, p < 0.001). Bland-Altman plot showed worse agreement between methods for higher values of QRS score, and a trend to overestimate percentage of MF. QRS score >= 5 was correlated to MF >= 12.3 g, MF >= 10% of left ventricular mass, and LVEF < 50%. QRS score >= 6 was associated to LVEF < 35% with good specificity. Patients classified as high risk by Rassi score had a median QRS score of 5 points (IQR: 3-9). Conclusion: Higher QRS score in CCC had a moderate correlation with higher burden of MF and worse LVEF. QRS score values tend to overestimate percentage of MF, whereas lower values of QRS seem to have a better correlation with CMR. Selvester scores above 5 or 6 points are associated with more LV impairment, and potentially related to worse outcomes. 111923 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Predictors of Status Epilepticus After Heart Transplantation GABRIEL ASSIS LOPES DO CARMO1, Barbara Carolina Silva Almeida1, Gabriela Zamunaro Lopes Ruiz1, Renato Braulio1, Ana Cristina Carioca1, Fabio Morato Castilho1, Claudio Leo Gelape1, Bruno Rodrigues Pereira1, Luiza Moreira Gomes1, Ana Carolina Sudario Leite1 (1) Universidade Federal de Minas Gerais (UFMG) Introduction: Neurological complications after heart surgeries are relatively frequent. Status epilepticus (SE) is particularly relevant due to its association with increased mortality. However, little is known about its pathogenesis and risk factors. Objectives: To evaluate the incidence of SE and identify its predictors after heart transplant. Methods: Prospect cohort of patients referred to heart transplantation in a university health facility in Brazil. Results: Between April of 2014 and November of 2021, 211 patients were referred to heart transplantation, median age 51 (40;58) and 73 (34,4%) females. In the early postoperative period, 28 (13.27%) patients had SE. Univariate analysis showed that INTERMACS 1 or 2 profile, OR = 4,88 (2,03-11,71), p < 0.001, and cardiorenal syndrome on renal replacement therapy (RRT), OR = 3,87 (1,59-9,39), p = 0.009, were associated with SE. Multivaltivariate analysis showed that only the INTERMACS 1 or 2 classification remained associated with SE, OR 3.88 (CI = 1.43-10.51), p = 0.008. The Hosmer-Lemeshow test had a value of p = 1.000. The occurrence of SE was not associated with increased mortality, OR 1.65 (CI = 0.61-4.45), p = 0.393. Conclusion: The occurrence of SE was only correlated with the INTERMACS 1 and 2 profile, a well know critical hemodynamic state with low cardiac output (CO). SE may be related to sudden increase in CO after cardiac transplantation, leading to an imbalance in cerebral blood flow. In the present analysis, SE was not correlated with higher mortality, possibly due to the small sample size. 111961 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Correlation between Modified Selvester Score and Fibrosis Mass After Acute Phase of Myocardial Infarction MARIA CATARINA DE MELO DIAS GUERRA1, Augusto Hiroshi Uchida1, Jose Antonio Franchini Ramires1, Eduardo Cavalcanti Lapa dos Santos1, Renata Avila Cintra1, Jurgen Beuther1, Nevelton Heringer Filho1, Tiago Augusto Magalhaes1, William Azem Chalela1, Guilherme Garcia1, Leonardo Filipe Benedeti Marinucci1, Carlos Eduardo Rochitte1 (1) Instituto do Coracao (InCor - FMUSP) Introduction: Myocardial infarction (MI) size is a key predictor of prognosis in post-MI patients. Cardiovascular magnetic resonance (CMR) is the gold standard test for MI quantification but is still limited due to restricted availability in daily routine. Previous studies have documented the capability of different electrocardiogram (ECG) markers for prognosis assessment soon after ST elevation myocardial infarction. Selvester QRS scoring detects scar, although the reported performance varies. A simplified version of this score showed comparable predictive value for infarct size in a prospective study including 201 patients at a median of 2 days after a revascularized MI (area under the curve = 0.64 vs. 0.67). Methods: Retrospective, observational, single-center study. The sample was obtained through analysis of medical records with a record of clinical diagnosis of MI who underwent CMR to assess myocardial viability. Those who did not present delayed enhancement with an ischemic pattern on CMR and those whose CMR revealed a diagnosis other than MI or did not have satisfactory image quality were excluded. Patients reporting a new acute coronary syndrome in the interval between the available ECG and the CMR were also excluded. The ECG performed 7 days after the infarction and with a maximum interval of 1 year from the CMR were analysed by an evaluator with extensive experience in electrocardiography. Results: The mean age of patients was 61.3 years and 75% were men. Conventional infarction identification through the presence of a pathological Q wave occurred in 172 of the 245 patients included (70.2%). In the subgroup of 192 patients in which CMR was already analyzed, the median modified Selvester score was 5 and the fibrosis mass was 23.2% +- 11.3 of the left ventricular mass. There was no statistically significant correlation between the modified Selvester score and fibrosis mass on CMR. Conclusions: After seven days of acute coronary syndrome, the modified Selvester score was not a predictor of fibrosis mass. This correlation had been previously described in smaller studies that evaluated this score at admission of acute MI. Intraventricular conduction disorders and ventricular hypertrophy are factors that may impact the correlation between the Selvester score and fibrosis mass. 111962 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Validation of SCAI Shock Classification in a Cohort of Heart Transplant Patients GABRIEL ASSIS LOPES DO CARMO1, Barbara Carolina Silva Almeida1, Gabriela Zamunaro Lopes Ruiz1, Renato Braulio1, Ana Cristina Carioca1, Fabio Morato Castilho1, Claudio Leo Gelape1, Bruno Rodrigues Pereira1, Luiza Moreira Gomes1, Ana Carolina Sudario Leite1 (1) Universidade Federal de Minas Gerais (UFMG) Introduction: The Society for Cardiac Angiography and Interventions (SCAI) shock classification was published in 2019, but not yet validated in patients referred to heart transplant. Objectives: To evaluate the association between different groups of the SCAI shock classification and the occurrence of death among patients undergoing heart transplant. Methods: Prospect cohort of patients referred to heart transplant in a university health facility in Brazil. Results: Between April 2014 and November 2021, 211 patients underwent heart transplantation, median age 51 (40;58) and 73 (34.4%) females. Baseline population characteristics were similar among the 5 different groups of the SCAI classification, with the exception of insulin-requiring diabetes mellitus (15.1%, 21.4%, 1.5%, 8.3% and 5.6%, p = 0.038), use of intra-aortic balloon prior to surgery (0.0, 4.6%, 20.0%, 55.6%, p < 0.001), days of hospitalization before surgery [0 (0;0); 1.5 (0;22); 30(15;59); 30(15;60); 39 (27;44)], platelet count [191000 (159250;246500); 214500 (172500;287500);221000 (176000;285500); 191000 (146000;250000); 184500 (139500;252500)] and RNI [1.51 (1.22; 2.39); 3.07 (1.65; 4.51); 1.46 (1.23; 2.37); 1.30 (1.12; 1.55) and 1.34 (1.18; 1.65)] respectively for groups A, B, C, D and E. Death occurred in 4 (7,4%) patients in group A, 2 (14,3) in group B, 4 (6,2) in group C, 15 (25,0%) in group D and 7 (38,9%). Compared to group A, patients in classification B had OR 2.083 (0.341-12.733), p = 0.595, those in group C OR 0.820 (0.195-3.444), p = 1.000, group D OR 4.167 (1.288-13.481), p = 0.012 and group E 7.955 (1.979-31.972), p = 0.004, for death. The ROC curve for the SCAI rating was 0.695 (0.590-0.799). Patients classified as D or E had an OR 4.832 (2.146-10.879), p < 0.001. Multivariate logistic regression analysis showed that group D or E classification was the only variable associated with mortality, OR 4.028 (1.397-11.610), p = 0.010. Conclusion: SCAI shock classification D or E was associated with increased risk of death after heart transplantation. The model had a limited capacity of discrimination, probably due to similar risk of death in groups A, B and C. 111972 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Leisure-Time Physical Activity and Cardiovascular Risk in Brazilian Adults: National Health Survey ANA CAROLINA MICHELETTI GOMIDE NOGUEIRA DE SA1, Elton Junio Sady Prates2, Deborah Carvalho Malta1 (1) Nursing Post Graduate Program. Nursing school, Federal University of Minas Gerais (UFMG). Belo Horizonte, MG, Brazil.; (2) School of Nursing at the Federal University of Minas Gerais (UFMG). Belo Horizonte, MG, Brazil. Introduction: Cardiovascular diseases (CVD) are the main cause of morbidity and mortality in the world and in Brazil and are caused by unhealthy lifestyles, genetic factors, social and health inequalities. These diseases cause disability and loss of quality of life. Consequently, this situation exacerbates the social and economic burden for society, governments and health services. Evidence has identified that physical inactivity is associated with increased coronary risk. However, there are still scientific gaps about the association of leisure-time physical activity (LPA) and cardiovascular risk in Brazil, even in view of the magnitude of CVD. The National Health Survey (PNS) performed laboratory tests and blood pressure (BP) measurements, thus, it was possible to explore, in an unprecedented way, the effect of AFL practice on cardiovascular risk in a representative sample of Brazilian adults. Objective: To analyze the association between AFL practice and cardiovascular risk in Brazilian adults. Methods: Cross-sectional study, with data from the PNS, between 2014-2015, in 8,952 adults. Prevalence and 95% confidence intervals were estimated for the practice of LPA stratified by sex, according to the Framingham risk score and its components. It was defined as sufficient AFL, the practice >=150 minutes per week of light or moderate intensity or 75 minutes per week of vigorous intensity. The risk score was classified as low, medium and high. Differences were evaluated using the chi-square test or analysis of variance (p <= 0.05). Results: The highest prevalence of sufficient LPA practice was associated with low cardiovascular risk in men (17.9%; 16.0-20.0) and women (12.0%; 10.9-13.4) (p <= 0.05). For risk score components, sufficient AFL prevalence was higher: in men aged 18 to 29 years (10.43%; 8.9-12.1), with high-density lipoprotein (HDL) between 35-44 mg/dL (9.8%; 8.5-11.3), total cholesterol (TC) between 160-190 mg/dL (11.2%; 9.8-12.8), untreated BP < 120 mmHg (11.4%; 9.9-13.1), who do not have diabetes (25.5%; 23.6-27.6) and are non-smokers (23.3; 21.4-25.3); and in women with HDL between 50-59 mg/dL (4.43%; 3.8-5.2), untreated BP < 120 mmHg (11.50%; 10.24-12.89) and not are smokers (16.2%; 14.9-17.5) (p <= 0.05). Conclusion: The practice of AFL is associated with a decrease in cardiovascular risk in Brazilian adults. Thus, it is important to encourage the practice of AFL in the country. These results can support CVD prevention actions and policies. 111973 Modality: E-Poster Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Impact of Antegrade Dissection and Re-Entry Technique on Coronary Chronic Total Occlusion Percutaneous Interventions SEBASTIAN DARIO PERALTA1, Marcelo Omar Bettinotti1, Guillermo Jubany1, Ezequiel Jose Zaidel1, Luis Murillo1, Juan Grieve Bruno1, Luis Carlos Sztejfman1, Matias Sztejfman1, Carlos Maximiliano Giuliani1, Ramon Gomes Marquez1, Pedro Piccaro de Olivera1, Alexandre Schaan de Quadros1 (1) LATAM CTO registry Background: The newest techniques for chronic total occlusions (CTO) percutaneous coronary interventions (PCI) may improve technical success. Purpose: To describe safety and efficacy of ADR (antegrade dissection and reentry) technique as initial revascularization strategy. Methods: Multicentric registry from Latin American countries. We analyzed baseline characteristics and outcomes of cases using ADR as primary strategy or bailout of antegrade wire escalation (AWE). Retrograde approach cases were excluded. Results: From 1875 patients analyzed, 50 were planned primary ADR (pADR) and 1825 planned primary AWE (pAWE). pADR was preferred in older patients, with a history of revascularization (CABG: pADR 33.3% and pAWE 13.4%, p < 0,001; PCI: 66.6% and 48.8% respectively, p = 0.012). Longer CTOs (30 mm [22-41] and 21 mm [15-30], p < 0.001), and moderate or severe calcification (62% and 42.6%, p = 0.008) were associated with the selection of pADR instead of pAWE. There was a significant correlation between increasing J-CTO score (Chi2 = 37, df = 5, p < 0.001), and use of pADR. pAWE had a success rate of 88.45%, and pADR of 76.67%. For pAWE and bailout ADR, the use of a dedicated device was related to the highest rates of success (92.31% and 82.69%, respectively). Short term outcomes were similar between groups. Conclusions: In Latin America, ADR was safe and effective, both as primary or bailout strategy, even when used for higher complexity lesions. The use of dedicated devices was related to a higher success rate. 111999 Modality: E-Poster Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Health Care Assistance to Patients with Acute Myocardial Infarction with St-Segment Elevation in Public Service in Salvador: Has There Been a Change During the COVID-19 Pandemic? POLLIANNA DE SOUZA RORIZ1, Jose Victor de Sa Santos3, Murilo Jorge da Silva3, Victor Luis Peixoto Pereira Botelho3, Marcelo Vincenzo Sarno Filho3, Bianca Aparecida Colognese3, Marcio Andrade Barreto Filho4, Rhanniel Theodorus Helhyas Oliveira Shilva Gomes Villar1 (1) Protocolo IAM - SAMU Salvador; (2) Hospital Ana Nery; (3) Universidade Federal da Bahia; (4) Escola Bahiana de Medicina e Saude Publica Introduction: An integrated healthcare system plays an important role in ST Elevation Myocardial Infarction (STEMI) assistance. Published data emphasize that the number of hospitalizations, diagnostic and therapeutic procedures performed in STEMI assistance in the pandemic context have decreased. Objective: Evaluate if there was a change in STEMI care assistance by the Acute Myocardial Infarction Protocol (AMIP) team, as reperfusion strategies and mortality in Salvador's health public system during the pandemic of Covid 19. Methods: Ambispective cohort of STEMI patients attended by the AMIP in Salvador. Epidemiologic data, assistance times, reperfusion strategies and intra-hospitalar mortality were compared between pre-pandemic period (jan/2019-feb/2020) and pandemic (march/2020-dec/2021) - groups I and II, respectively. Statistical significance was considered for p < 0.05. Results: Group I was composed of 542 patients and group II of 932. The mean age and male sex frequency were similar in both groups. There was a higher frequency of hypertension (73.2% x 67.8%, respectively; p = 0.03) and typical A/B pain (91.2% x 85%, respectively; p = 0.01) in group I. Other comorbidities, clinical presentation, Killip and GRACE showed no differences between groups. Controversially, there was no difference in the median symptom-first medical contact time [I-120 (50-270)min x II-123 (60-268.5)min, p = 0.32]. Door-to-ECG time was even shorter in group II [29 (14-70)min] compared to I [35 (16-92.7)min], p = 0.01. There was a shorter door-to-needle time in group II compared to I [111.5 (76-174.8)min x 140 (91.8-202.3)min, respectively; p = 0.002] as well as door-to-balloon time [219 (169.3-317.8)min x 253 (175.8-356.5)min; p = 0.03]. Regarding reperfusion strategies, more patients underwent Percutaneous Coronary Intervention (PCI) in II x I (78.3% vs. 73.5%, p = 0.04), due to a higher frequency of pharmaco-invasive strategy in the second group (II-17.7% x I-3.2%, p < 0.001). There was no difference for primary PCI between groups (57.3% I x 58.8% II; p = 0.64). In-hospital mortality did not differ between the groups (I-17.3%) and (II-16.1%), p = 0.56. Conclusion: During the pandemic, there was a switch in the reperfusion strategy supported by AMIP in order to offer more room to fibrinolysis. The troubled scenario caused by the COVID-19 pandemic did not have a major impact on mortality of patients with STEMI in Salvador. 112000 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Newborn Pulse Oximetry Screening Prevalence in a Nationwide Complex Survey Sample: An Assessment of Congenital Heart Diseases Early Detection Program at the Regional Level in Brazil ARN MIGOWSKI ROCHA DOS SANTOS1, Arn Migowski1, Gustavo Tavares Lameiro da Costa1, Helena Cramer Veiga Rey1 (1) Instituto Nacional de Cardiologia (INC) Introduction: In Brazil, early neonatal mortality is responsible for more than 50% of deaths in the 1st year of life and congenital heart diseases accounts for 40% of malformations. Newborn pulse oximetry screening(POS) test for critical congenital heart defects between 24-48 hours of life is non-invasive, easy-to-perform and highly specific. Objectives: To estimate the prevalence of POS in Brazil, as well as identify the factors associated with it and the prevalence of positive screening results. Methods: Prevalence was estimated based on results of the most recent National Health Survey, a nationwide population-based cross-sectional Brazilian study. The adjusted marginal prevalence ratios were estimated from a logistic regression model based on Wilcosky & Chambless approach(R prLogistic package). Results: The prevalence of POS was 66.3% (95% CI: 65.5-67.1; N = 3,140,023). The screening prevalence in children born in private funded hospitals (PFHs) was higher than in the National Unified Health System (SUS): 78.1% (76.7-79.5) vs 61.1% (60.2-62.1), respectively. Major regions comparison shows important differences. In the North the prevalence in PFHs (64.9%; 59.7-70.1) was lower than in the South (82.5%; 79.4-85.6) and the Southeast (81.5%; 79.3-83.6) and it is even lower when compared with SUS in the North (44.0%;42.4-45.6). An ordinance was published in Aug 2018, allowing SUS to finance after-screening diagnosis to investigate congenital heart diseases, increased the prevalence of screening in SUS: 57.6% (56.2-59.1) before vs 64.6% (63.3-65.9) after the ordinance. Prevalence of positive screening tests was 9.2%(8.9-9.5) in SUS and 7.8% (7.3-8.3) in the PFHs. The proportion of these newborns that underwent complementary exams after screening was lower in SUS than in the PFHs (40.8%; 40.5-41.1 vs 57.2%; 56.7-57.7). In the multivariate model, the main independent predictors of POS were the prevalence of other newborn screening tests, specially the red eye reflex (PR = 2.03; 1.90-2.16) and newborn hearing test (PR = 1.75; 1.64-1.87). Conclusions: Inequalities were found in the prevalence of screening between major regions, as well as in SUS and PFHs. Government financial incentive has reduced this inequality between public and private, although the percentage of complementary exams after positive screening was also unequal. The main independent predictors of screening prevalence were those related to the organization of health services. 112004 Modality: E-Poster Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Out-Of-Office Measurement of Blood Pressure: Practice, Patient Adherence and Impact on Blood Pressure Control in a High-Complexity Public Outpatient Facility ANTONIO GABRIELE LAURINAVICIUS1, Antonio Gabriele Laurinavicius1, Alessandra Cristina Vieira1, Julia Luzo Elias Thame1, Rafael Goncalves Zimmer1, Henrique Marino de Medeiros1, Jorge Tadeu Campos Paixao1, Fernanda Consolim Colombo1, Marcio Goncalves Sousa1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Out-of-Office Measurement of Blood Pressure (BP) is recommended in addition to office BP for the diagnosis and follow-up of hypertensive patients. Ambulatory Blood Pressure Monitoring (ABPM); Home Blood Pressure Monitoring (HBPM); and Self-Monitoring of BP (SMBP) are the currently available options and their indication may vary according to the context. The aim of the present study was to assess how Out-of-Office Measurement of BP takes place in clinical practice and its impact on BP control in a public tertiary outpatient clinic. Methods: We evaluated 225 consecutive patients seen at a high-complexity public outpatient facility (mean age: 66.7 +- 11.9 years; female: 62.7%). All patients were routinely requested to perform SMBP according to a prespecified institutional protocol. ABPM and HBPM were indicated for selected cases at the discretion of the attending physician. Patient Adherence to Out-of-Office Measurement of BP was labeled into 5 possible categories: a) No Measurement; b) ABPM; c) HBPM; d) Adequate SMBP e) Inadequate SMBP. Patient Adherence was also stratified according to sex, age, number of antihypertensive drugs, schooling, length of follow-up at the facility, comorbidities and availability of BP monitor at home. Rates of BP control were related with Patient Adherence, as well as with the aforementioned variables. Results: 87.5% of the study population reported having a BP monitor at home. However, adding up the 5 possible categories, adequate Out-of-Office Measurement of BP was available in only 46.7% of the sample (40.9% of the patients did not bring any measurement; 13.8% underwent ABPM; 32.9% adequate SMBP; 12.4% inadequate SMBP; 0% HBPM). Availability of a BP monitor at home (p < 0.001) and the number of antihypertensive drugs in use (p = 0.019) were strongly associated with adherence to SMBP. Prevalence of smoking was 2 folds higher (7.5% vs 3.4%) in those who returned without SMBP. Rate of BP control based on office BP was 42.6% (79.5% of the sample was under >=3 classes of antihypertensive drugs). Out-of-office BP measurements were not associated with higher rates of BP control (p = 0.377), but allowed to identify a White Coat Effect (WCE) in 1 out of 3 patients with uncontrolled BP according to office BP (WCE prevalence: 29% among uncontrolled patients vs 3.9% among controlled ones. Conclusions: Out-of-Office Measurement of BP is still an unmet need in the treatment of hypertension. 112035 Modality: E-Poster Researcher - Non-case Report Category: CARDIO-ONCOLOGY Avaliation of Glycolytic Metabolism and Myocardial Deformation of the Left Ventricle in Patients with Lymphoma, Pre and Post Chemotherapy with Anthracyclines MONICA DE MORAES CHAVES BECKER1, Gustavo Freitas Alves de Arruda1, Diego Rafael Freitas Berenguer1, Roberto de Oliveira Buril1, Felipe Alves Mourato1, Paulo Jose de Almeida Filho2, Brivaldo Markman Filho1, Simone Cristina Soares Brandao1 (1) Universidade Federal de Pernambuco; (2) Real Hospital da Beneficencia Portuguesa Introduction: Studies have suggested that the assessment of cardiac 18F-FDG uptake may be an early metabolic marker of cardiotoxicity. Echocardiography is the method of choice for the evaluation and follow-up of patients undergoing chemotherapy (CT) with anthracyclines, especially through the Global Longitudinal Strain (GLS) technique, which would change earlier than the drop of the left ventricular ejection fraction (LVEF) in patients with reduced myocardial performance. Objective: The objective of this study was to show the cardiac metabolic and functional behavior pre and post-CT with anthracyclines, in patients with lymphoma and to evaluate the relationship between metabolic alteration and cardiac performance. Methods: 18F-FDG PET-CT and strain echocardiography were prospectively performed before and after CT. On PET-CT, the maximum standardized uptake (SUV) value of 18F-FDG was measured in the interventricular septum (IVS) and aorta - blood pool. An increase above 30% in the uptake of 18F-FDG in the IVS was considered significant. On echocardiography, LVEF and GLS were measured. After CT, patients were divided into two groups according to the drop in GLS >=15% from baseline. Data were compared post-CT and between groups. Results: Twenty-four consecutive patients were selected (mean age 44,5 +- 18 years, 58,3% female and 66,7% with non-Hodgkin's lymphoma). The mean LVEF did not show significant difference before (63,5% +- 4,6%) and post CT (64,9% +- 4.4%). Subclinical left ventricular dysfunction (GLS drop >=15%) occurred in seven (29,2%) patients, during or after CT. Significant increase in IVS FDG uptake occurred in 13 (54,2%) patients. The pre-CT median SUV maximun SIV/SUV maximun aorta ratio increased from 0.84 (IQ 0.73-1.01) to 1.06 (IQ 0.84-1.93) after CT, p = 0.02. However, when we compared this relationship between the groups, there was no significant difference. Conclusions: In this casuistic, we did not observe a significant reduction in LVEF after chemotherapy. However, about 29% of patients presented a decrease in cardiac performance assessed by the strain echocardiography and more than half had a metabolic change in IVS. The relationship between metabolic alteration and subclinical cardiac performance needs to be better clarified. 112042 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Superior Periareolar Access for Minimally Invasive Cardiac Surgery ADRIANO MARCIO DE MELO MILANEZ1, Marina Coelho Feitosa2, Yury Pifano Varela2, Josue Viana de Castro Neto3, Flavio Duarte Camurca1 (1) Cardiovascular surgeon, Cardiovascular Surgery Department, Hospital Antonio Prudente, Fortaleza, Ceara, Brazil.; (2) Medical school student, The University of Fortaleza - UNIFOR, Fortaleza, Ceara, Brazil; (3) Cardiovascular surgeon, Professor of Surgery, The University of Fortaleza - UNIFOR, Fortaleza, Ceara, Brazil. Introduction: The Right Inferior Periareolar Access (RIPA), also known as the Brazilian Technique, has been progressively applied in minimally invasive cardiac surgery (MICS) for atrioventricular valve and septal defect procedures. It provides good functional and aesthetic results, while using a similar fourth intercostal access when compared to the usual inframammary minithoracotomy. We aim to describe a Right Superior Periareolar Access (RSPA), performed one intercostal space above the RIPA, with advantages. Methods: The RSPA consists of a videoassisted minithoracotomy in the 3rd intercostal space through a superior periareolar incision of 3 cm enlarged by a wound protector (Image 1). The cardiopulmonary bypass was established through a femoral platform and cannulation of the right internal jugular vein was added when necessary. A 5 mm port was inserted through the 2nd intercostal space for non dominant hand instrumentation initially and for clamp placement afterwards. The camera port was inserted through the 5th intercostal space. This technique was performed in 39 patients: 30 with atrial septal defects, 5 submitted to mitral valve reconstruction and 4 undergoing mitral valve replacements. Twenty four were females. The mean age was 40. Results: The RSPA provided adequate surgical fields for all procedures. The cardioplegia infusion in the ascending aorta was easily done. Conversion to full sternotomy was necessary in one patient due to bleeding. The median lenght of intensive care unit stay was 1 day and the median postoperative hospital stay was 3 days. There were no postoperative wound infections and no postoperative mortality. The RSPA provided easy access to cardiovascular structures, contributing to effective, functional and safe procedures. The resulting surgical scars were very subtle, and did not compromise the areola. Conclusion: The MICS procedures applying the RSPA technique were effective and safe. Other remarkable advantages were adequate access to the aorta and atriums, low lenght of stay in the intensive care unit and in the hospital and good aesthetic results. 112055 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Prevalence of Fragmented QRS and its Correlation with Fibrosis Mass After Acute Myocardial Infarction MARIA CATARINA DE MELO DIAS GUERRA1, Augusto Hiroshi Uchida1, Jose Antonio Franchini Ramires1, Eduardo Cavalcanti Lapa dos Santos1, Renata Avila Cintra1, Jurgen Beuther1, Nevelton Heringer Filho1, Tiago Augusto Magalhaes1, William Azem Chalela1, Guilherme Garcia1, Leonardo Filipe Benedeti Marinucci1, Carlos Eduardo Rochitte1 (1) Instituto do Coracao (InCor - FMUSP) Introduction: Fragmented QRS (fQRS) is an easily evaluated electrocardiographic parameter and has been associated with alternation of myocardial activation due to myocardial scar. Methods: Retrospective, observational, single-center study. The sample was obtained through analysis of medical records with a record of clinical diagnosis of myocardial infarction (MI) who underwent cardiac magnetic resonance (CMR) to assess myocardial viability. Those who did not present delayed enhancement with an ischemic pattern on CMR and those whose CMR revealed a diagnosis other than MI or did not have satisfactory image quality were excluded. Patients reporting a new acute coronary syndrome in the interval between the available electrocardiogram (ECG) and the CMR were also excluded. The ECG performed 7 days after the infarction and with a maximum interval of 1 year from the CMR were analysed by an evaluator with extensive experience in electrocardiography. Results: The mean age of patients was 61.3 years and 75% were men. Conventional infarction identification through the presence of a pathological Q wave occurred in 172 of the 245 patients included (70.2%). Fragmentation of the QRS complex was identified in 102 of the 245 patients included (41.6%). The prevalence of fQRS was significant even in smaller MI and no correlation was found between the presence of fQRS and the mass of fibrosis on CMR. A higher prevalence of fQRS was observed in infarcts predominantly in the lateral and anterior walls (figure 1). Conclusions: This study revealed a significant prevalence of fQRS in patients after the acute phase of infarction, even in those with a lower mass of fibrosis. Although the analyzed sample of lateral infarctions is still limited, the high prevalence of fQRS may be a relevant finding, considering the low sensitivity of the classic criteria for identifying lateral infarction on the ECG. Figure 1 - Prevalence of QRS fragmentation according to the wall most affected by the infarction. 112063 Modality: E-Poster Researcher - Non-case Report Category: CARDIOGERIATRICS The Clinical Features of Acute Heart Failure in Octogenarians ALEXANDRA CORREA GERVAZONI BALBUENA DE LIMA1, Luana de Oliveira Alves1, Laila Morais Nahass Franco1, Pedro Pinto Machado2, Pedro Henrique Parcianello Teixeira2, Luciana Bartolomei Orru D'Avila1 (1) North Wing Regional Hospital - Brasilia - Brazil; (2) School of Health - Brazil. Background: Heart failure (HF) increases significantly in relation to advancing age. With aging, not only do age-related, morphological, and physiological cardiovascular changes predispose to HF, there is also increased prevalence of comorbid conditions that compound cardiac limitations (e.g., renal insufficiency) and others that tend to overwhelm limited cardiovascular reserves (e.g., infections and ischemia). The HF among very old adults, the prevalence, the complications in acute HF demand more studies. Objective: Evaluate the clinical features and prognostic evolution of individuals 80 years and older with acute HF. Methods: Retrospective and observational study of patients 80 years or older, hospitalized with acute HF at North Wing Regional Hospital, Brasilia, Brazil, January 2017 to May 2020. Patients who did not meet the clinical criteria of HF, with missing or incomplete information in the medical record or were not accessible by telephone were excluded. The minimal follow-up were 12 months and final date were 05.21.2021. Clinical profiles, clinical history, blood test, and mortality were analyzed. The patients were divided into groups: 80 to 84 years and >=85 years. Results: A total of 119 individuals (66 and 53) were included, 45% and 47% male, 92% and 83% hypertensive. The mean age of the groups were 81.7 +- 1.3 years (80-84) and 88.6 +- 3.5 years (85-97), hemoglobin 11.9 +- 2.4 mg/dL and 10.8 +- 2.0 mg/dL, creatinine 1.44 +- 1.9 mg/dL and 1.78 +- 1.4 mg/dL, left ventricular ejection fraction 51.8 +- 15.7% and 58.6 +- 11.8%, and follow-up 29.1 +- 25.9 days and 28.4 +- 24.6 days. The presence of pulmonary congestion 40% and 45%, peripheral edema 45% and 43%, and atrial fibrillation (AF) 34% and 35%. During the hospitalization, hemodialysis 15% of both groups, vasoactive drugs 28% and 18%, intensive care unit 45% and 39%, and mortality rate 21% and 18%. In multivariate analysis deaths were related to hypertension (HR = 0.54, 95%CI = 0.29-0.98, p = 0.046), pulmonary congestion (HR = 3.38, 95%CI = 1.97-5.79, p = 0.000), peripheral edema (HR = 4.12, 95%CI = 2.30-7.38, p = 0.000), AF (HR = 0.58, 95%CI = 0.34-0.98, p = 0.043), and hemoglobin (HR = 0.84, 95%CI = 0.75-0.95, p = 0.007). Conclusion: In our study simple clinical features as pulmonary congestion, peripheral edema and hemoglobin showed association with mortality. Consideration of disease prognosis according to factors that predict mortality can help to better define the care plan and promote palliative and supportive care. 112078 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Sedentary Behavior in Adolescents from Public Schools of Goias During the COVID-19 Pandemic PRISCILA VALVERDE DE OLIVEIRA VITORINO1, Alice PInheiro Ribeiro1, Edison Nunes Pereira2, Gustavo Carvalho Marcelino1, Ana Carolina Arantes2, Ademir Schmidt1, Weimar Kunz Sebba Barroso2 (1) Pontificia Universidade Catolica de Goias; (2) Universidade Federal de Goias Introduction: Sedentary behavior (SC) is a habit present in worldwide, with increasing percentages in the last decade, especially among adolescents. With the COVID-19 pandemic, CS increased, especially due to social isolation and school closures. Objetives: Carachterize adolescens regarding sociodemographic and economic conditions, aspects related to school and work and general health; classify adolescents in terms of SC and compare CS according to gender. Method: Analytical cross-sectional study, conducted with adolescents (10 to 19 years), enrolled in 19 schools of Goias. Electronic data collection took place from November 2020 to August 2021. The form contained questions about personal, sociodemographic, lifestyle and CS. Two cutoff points were considered for SC: >=6 and >= to 3 hours/day. The project was approved by Ethics Committee. Descriptive analysis and comparisons were performed using pearson's Student and Chi-square T tests. Significance level p < 0.05 was considered. Results: We evaluated 167 students with a mean age of 15.3 DP 2.1 (Table 1). The frequencies of SC 89.1% and 52.7% at the cutoff points of 6 and 3 hours/day, respectively. Conclusions: The sample was characterized by adolescents who did not work, were mainly from social classes B and C and had a low frequency of bad health habits. There was no difference in the frequency of SC in relation to the variables evaluated. 112101 Modality: E-Poster Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Religiosity in Adhesion to Treatment of Pilgrims with Hypertension CELIDA JULIANA DE OLIVEIRA1, Heryka Laura Calu Alves1, Gabriela de Sousa Lima1, Erica Sobral Gondim1, Emiliana Bezerra Gomes1 (1) Universidade Regional do Cariri - URCA Introduction: Hypertension evolves slowly and is asymptomatic, so it does not usually receive the proper care, resulting in poor adherence to treatment and an increase in cardiovascular events. It is a disease that requires changes in lifestyle for adherence to treatment, which is influenced by several factors, such as religiosity, which includes people's beliefs, attitudes and values. Therefore, the pilgrimage of Padre Cicero stands out, a religious manifestation that attracts thousands of faithful to the municipality of Juazeiro do Norte-CE, in which the attendance to pilgrims because of the elevation of blood pressure is a constant, making it necessary to study the relationship between religiosity and adherence. Objective: To investigate the influence of religiosity in the treatment adherence of hypertension by pilgrims. Method: Cross-sectional, qualitative, carried out in Juazeiro do Norte, between September 9 and 15, 2018. The question was: "Does religion influence you to comply with treatment for high blood pressure?". The data collected were organized into thematic categories. The study was approved by the Ethics Committee under opinion number 2,753,051. Results: 338 pilgrims self-reported with hypertension were investigated, male (62.43%), retired (71.06%) and mean age of 64.5 years. When questioned about the influence of religion on treatment, three categories emerged: Category 1 "Faith": Faith was answered as the influence of religion on compliance with treatment, either alone or in a complementary way, also as a cure for hypertension. Category 2 "I pray for improvement": Prayers are the most cited as influencing treatment, for comforting, improving thoughts and guiding behaviors, such as waking up to pray and taking medication. Category 3 "Religion is above all": Church and masses were cited as contributors. Pilgrims report feeling good and associating religious practices with treatment, combining medication intake times with church participation. The people who are in this space represent a support network, especially the priest, by encouraging self-care related to the treatment. Final Considerations: It was noticeable that the pilgrimage and its elements influence the perception of health, illness and treatment. Thus, they can be used as beneficial means of promoting health and adherence to therapy through strategies that enhance the spiritual dimension. 112117 Modality: E-Poster Researcher - Non-case Report Category: PHYSICAL EDUCATION Exercise Training in Patients with Chagas Cardiomyopathy: A Systematic Review of Randomized Controlled Trials FABIO SILVA MARTINS DA COSTA1, Henrique Silveira Costa2, Lucas Frois Fernandes Oliveira2, Matheus Ribeiro Avila2, Pedro Henrique Scheidt Figueiredo2, Mauro Felippe Felix Mediano3, Luciano Fonseca Lemos de Oliveira1, Manoel Otavio Costa Rocha1 (1) Universidade Federal de Minas Gerais - UFMG; (2) Universidade Federal dos Vales do Jequitinhonha e Mucuri - UFVJM; (3) Fundacao Oswaldo Cruz - FIOCRUZ Introduction: Patients with Chagas cardiomyopathy (ChC), in addition to having a worse prognosis compared to other cardiomyopathies, can have important consequences, including reduced functional capacity and quality of life. The exercise training (ET) has emerged as an adjuvant option for treatment of ChC, relieving dyspnea and fatigue caused by heart failure. This study aimed to discuss the main findings of effect of ET in patients with ChC, focusing on the functional capacity, hemodynamic and autonomic function, musculoskeletal system, myocardial function and morphology, and health-related quality of life (HQoL). Methods: This is a systematic review using the descriptors: ("Chagas disease" OR "chronic Chagas cardiomyopathy") AND ("exercise training" OR "cardiac rehabilitation"). A literature search of the MEDLINE, LILACS, Web of Science, CINAHL, Scopus, PEDro and EMBASE was performed with no data or language restrictions. The study was registered in PROSPERO database (CRD CRD42017064912) and edited following in guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: A total of 5 papers (screened from 1.169 studies) reached the inclusion criteria and were included in the present review. The patients with ChC submitted to ET presented improvement of functional capacity (increase in the VO2peak and the walked distance in the 6-minute walk test, but did not reduce the ventilatory efficiency given by VE/VCO2slope), hemodynamic and autonomic function (reduce the HR at rest but do not change the blood pressure; slight increase in the HRV in patients with reduced LVEF and better improvements in the autonomic balance given by increase in the parasympathetic activity and reduction in the sympathetic activity over the heart in patients with preserved LVEF and autonomic dysfunction), musculoskeletal system (increase in the cross-sectional and number of type I fiber, reduce the genes expression involved in the muscle atrophy process, increase skeletal muscle perfusion) and the HQoL (improve domains of vitality and emotional aspects). However, no changes in the myocardial function and morphology were observed. Conclusion: In conclusion, the ET as a low-cost non-drug therapy option seems to provide important benefits in association with the classic treatment of patients with ChC, however, more studies are warranted to confirm these results. 112137 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Safety and Effectiveness of Conduction System Pacing (His-Bundle Pacing and Left Bundle Branch Pacing) as a First Option for Cardiac Pacing CHARLES SLATER1, Luiz Eduardo Camanho1, Eduardo Benchimol Saad2, Luiz Antonio Oliveira Inacio Jr2, Lucas Carvalho Dias1, Gustavo Vignoli Santos2, Ricardo Mourilhe-Rocha1 (1) State University of Rio de Janeiro (UERJ), Rio De Janeiro, Brazil; (2) Hospital Pro Cardiaco, Rio De Janeiro, Brazil Background: Conduction system pacing (CSP) (His bundle pacing and left bundle pacing) is a group of techniques intended to achieve cardiac pacing with a narrow QRS complex. The safety and effectiveness of this technique are not yet entirely understood. Purpose: To describe the implant findings and safety profile of CSP as a first option after 4 years in a single center. Methods: In a period of 42 months, 214 patients were submitted to CSP as a first strategy to restore AV synchrony (pacemakers for AV block or sinus node dysfunction) or as a resynchronization (CRT) strategy (for patients with heart failure and bundle branch block). CSP was implanted in lieu of a conventional right ventricular lead in pacemaker cases, and in addition or in lieu of a coronary sinus lead, in CRT cases, depending on the technical and anatomical findings. Results: The mean age was 76.7 +- 16.4 years, 65% males. 162 patients implanted a CSP lead for a dual-chamber pacemaker, 3 patients for a single chamber pacemaker, 32 patients for CRT-D (CSP lead replacing the coronary sinus lead with a defibrillator), and 13 patients for an optimized CRT (CSP lead plus coronary sinus lead). In 16 patients (7.4%) the technique of choice was His bundle pacing. One patient (0.4%) had subacute lead dislodgement, being submitted to repositioning. 4 patients - intended for CRT (1.8%) didn't meet the criteria for His Bundle pacing or left bundle pacing, being submitted to conventional coronary sinus lead placement. There were 10 cases (4.6%) of confirmed lead perforation during the lead septum insertion, with prompt repositioning, all uneventful. No pericardium effusion related to lead perforation was observed. One patient (0.4%) had a pneumothorax, requiring chest tube drainage. Conclusion: Conduction system pacing as a first strategy is a feasible, effective and safe technique, both for pacing and for resynchronization purposes, with complication rates comparable to conventional implantation. 112166 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Does Respiratory Muscle Strength and Diaphragmatic Mobility Influence Glittre ADL-Test Performance in Patients with Heart Failure? DANIELLA CUNHA BRANDAO1, Bruna T.S. Araujo1, Kamyla Maria Alcantara Silva Alves1, Armele Dornelas de Andrade1, Daniella Cunha Brandao1 (1) Universidade Federal de Pernambuco Introduction: Studies relating respiratory muscle strength and diaphragmatic mobility in heart transplant patients are scarce, especially when correlated with submaximal exercise tests, such as the Glittre ADL-Test, which is still poorly investigated in this population. Purpose: To investigate whether the time required to perform the Glittre ADL-Test correlates with respiratory muscle strength and diaphragmatic mobility. Methods: This was a cross-sectional study with 38 adult individuals aged 21 to 65 years, diagnosed with HF of all etiologies and with reduced ejection fraction. The performance of the Glittre ADL-Test followed the standardization of the literature, using the Total Time to complete the five laps of the test. The assessment of respiratory muscle strength was made by a digital manovacuometer and diaphragmatic mobility was measured by ultrasound in the M. mode. Results: The mean Glittre ADL-Test time was 286.5 seconds and showed significant correlations with maximal inspiratory pressure (MIP) (r = -0.445 - p < 0.01) and maximal expiratory pressure (MEP) (r = -0.531 - p < 0.01) and with diaphragmatic mobility (r = -0.361 - p < 0.05). Conclusions: Our findings suggest an inverse relationship between respiratory muscle strength and diaphragmatic mobility with Glittre ADL-Test performance. If respiratory muscle strength and diaphragm muscle movement are lower, the time taken to complete the test will be longer, suggesting that increased respiratory work may potentiate peripheral muscle fatigue. The impairment of respiratory muscles seems to have important implications on the performance of HF individuals in their daily activities, confirming the need for early identification of patients with respiratory muscle weakness, enabling a targeted intervention in this population. Support: Edital PROPG-UFPE 230760186722020-32; CNPq 421656/2021-7 and FACEPE 0801-4.08/21. 112169 Modality: E-Poster Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Conduction System Pacing as a First Strategy for Cardiac Resynchronization Therapy in Heart Failure CHARLES SLATER1, Luiz Eduardo Camanho1, Eduardo Benchimol Saad2, Luiz Antonio Oliveira Inacio Jr2, Lucas Carvalho Dias1, Gustavo Vignoli Santos2, Ricardo Mourilhe-Rocha1 (1) State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil; (2) Hospital Pro Cardiaco, Rio de Janeiro, Brazil Background: Conduction system pacing through direct His bundle of left bundle stimulation is a new alternative to achieve adequate CRT in patients with heart failure with reduced ejection fraction (HFrEF). Purpose: To describe the short and medium term outcomes of CRT through direct conduction system pacing in a single center. Methods: 53 consecutive patients who underwent CRT through direct stimulation of the His bundle or left bundle branch were retrospectively evaluated. All presented in functional class III/IV (NYHA). The CRT response criteria were: improvement of functional class and reverse remodeling criteria (increase in ejection fraction (EF) >10% and/or decrease in left ventricular end-systolic diameter (LVESD) >15%). The patients were evaluated at 1 and 3 months and every six months after the procedure. Results: The mean age was 76,4 +- 14,8 years, 65% males, 42% Ischemic cardiomyopathy. Left bundle branch block (LBBB) was observed in 98% and mean QRS duration was 169 ms; average EF: 28%; mean LVESD and left ventricular end-diastolic diameter (LVEDD) was 53 and 68 mm, respectively. Direct His bundle pacing was the technique of choice in 5 patients, while left bundle branch pacing was used in 48 patients. There were five patients where His bundle pacing of left bundle branch pacing criteria was not met, being submitted to conventional CRT through coronary sinus branches. The mean follow up time was 21 months. Mean QRS duration was significantly shorter after the procedure (128 ms). Improvement of functional class was found in 85,7% of patients. Reverse remodeling criteria was found in 70,5% of patients. 4 patients progressed to end-stage HF and subsequent death. Conclusion: CRT through conduction system pacing is a valid alternative to conventional CRT, with promising results, allowing cardiac resynchronization in patients with HFrEF. 112201 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Long-Term Mortality Predictors in Hospitalized COVID-19 Patients using Machine Learning Model BRUNO FERRAZ DE OLIVEIRA GOMES1, Thiago Moreira Bastos da Silva2, Leticia de Sousa Peres1, Iliana Regina Ribeiro Menezes1, Nathalia Duarte Camisao1, Mariana Moreno Canario da Silva1, Renata Mexias Abdala Felix1, Giovanni Possamai Dutra1, Anna Butter1, Henrique Custodio Goudar1, Joao Luiz Fernandes Petriz1, Glaucia Maria Moraes de Oliveira2 (1) Hospital Barra D'Or; (2) Universidade Federal do Rio de Janeiro Introduction: Several studies have already scored the predictors of in-hospital mortality in patients hospitalized for COVID-19. 2 years after the beginning of the pandemic, few studies have evaluated predictors of long-term mortality. Objectives: To evaluate clinical and laboratory characteristics predictors of mortality using machine learning techniques. Methods: Retrospective cohort study with patients who were hospitalized with a confirmed diagnosis of COVID-19. Comorbidities, laboratory tests, vaccination status, and clinical characteristics were evaluated. The primary outcome of this study is all cause death occurring in the hospital or after hospital discharge. We used the classification tree model for the survival outcome, available in RStudio 2021.09.0. Results: 1454 patients were included, mean age of 59.8 +- 17.0, 62.6% men. There were 269 deaths (18.5%) during the study period (mean follow-up = 338 +- 209 days). 44.7% of patients had myocardial injury. The following predictive variables were selected by the method: use of mechanical ventilation, age, platelet count at discharge, CRP at discharge, myocardial injury, SAPS3 score, d-dimer peak of hospitalization, dementia, chronic renal failure, COVID-19 vaccination, and use of anticoagulation therapy. The model is available in the figure. Conclusion: In patients hospitalized for COVID-19, patients who required mechanical ventilation, with high CRP at discharge and higher age had the worst long-term prognosis. Other markers have shown promise in predicting more severe patients, such as platelet count at discharge and the occurrence of myocardial injury. 112202 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Ultrasound Guided Vascular Access for Cardiac Devices Implantation - Safety and Efficacy Results CHARLES SLATER1, Luiz Eduardo Camanho1, Eduardo Benchimol Saad2, Luiz Antonio Oliveira Inacio Jr2, Lucas Carvalho Dias1, Gustavo Vignoli Santos2, Ricardo Mourilhe-Rocha1 (1) State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil; (2) Hospital Pro Cardiaco, Rio de Janeiro, Brazil Background: Vascular access is the first step to perform cardiac device (CD) implantation. However, vascular access-related complications still remain a major cause of complications in CD implantation, increasing risk, costs, and hospitalization time. Ultrasound has become an important tool in helping vascular access, and its use has increased recently for CD implantation. Purpose: To describe the results after 4 years of US-guided vascular access for implantation of CD. Methods: Over a period of 50 months, 627 patients (average age 77,1 +- 14,6 years - interquartile range: 13 years) were submitted to CD implantation (271 dual-chamber pacemakers, 9 single-chamber pacemakers, 24 CRT-P's, 167 conduction system pacemakers (His bundle pacing or left bundle pacing), 63 CRT-D's, 46 dual-chamber ICD's, 2 single-chamber ICD's, 4 lead implantations and 41 upgrades for CRT), in a total of 1282 US-guided punctures (longitudinal "out of plane" axillary vein approach) using a "Point of Care" US machine with a 12MHz probe protected with a sterile cover. All punctures were performed on intact skin, followed by an incision. Chest radiography and pulmonary ultrasound were performed in the search for complications immediately after the procedure and the next morning, before discharge. Results: Vascular access was successful in all cases. In 11 cases (1,75%) there was limiting vascular obstruction, requiring contralateral vascular access to complete the procedure. US image also allowed alternative approaches, such as access to a supraclavicular vein (3 cases/0,47%) in patients with complete obstruction of the axillary vein; and cephalic vein puncture (4 cases/0,63%) when the axillary vein was too deep. Pneumothorax was found in one patient (0,16%) through the pulmonary US the next morning and submitted to chest drainage with no further complications. No haemothorax was found in this sample. Conclusion: US-guided vascular access technique allows safe implantation, with complication rates considerably lower than that related in literature. 112215 Modality: E-Poster Researcher - Non-case Report Category: PHYSIOTHERAPY Performance in Glittre ADL-Test Associates with Maximum Functional Capacity in Heart Failure Patients: A Cross-Sectional Study DANIELLA CUNHA BRANDAO1, Jessica Costa Leite2, Bruna T.S. Araujo1, Armele Dornelas de Andrade1, Daniella Cunha Brandao1 (1) Universidade Federal de Pernambuco; (2) UNIFACISA Introduction: The Glittre ADL-Test appears as one more test option to assess submaximal exercise tolerance in heart transplant patients. Purpose: To verify the association between the time spent in the Glittre ADL-Test with the variables of the Cardiopulmonary Exercise Test (CPET). Methods: A cross-sectional study evaluating 53 male and female subjects with Heart Failure (HF), NYHA (New York Heart Association) II-III and left ventricular ejection fraction <45%. The individuals performed the CPET on a treadmill with ramp protocol to evaluate the maximum functional capacity and on another day the Glittre ADL-Test, considering the total time to complete the five rounds of the test. A minimum interval of 24 hours and a maximum of 7 days between the tests was respected. Results: Glittre ADL-Test time was negatively and moderately associated with peak oxygen uptake (VO2peak) (r = -0.48; p = <0.001) and oxygen uptake at the first ventilatory threshold (r = -0.475; p = <0.001), besides a low negative association with the time to reach VO2peak (r = -0.345; p = 0.014). Conclusions: We can suggest from the results obtained that the Glittre ADL-Test is an accessible method for assessing individuals with HF and correlates with the oxygen uptake measured by CPET. As clinical implications we have: The Glittre ADL-Test can be a fast and economical alternative for estimating the functional capacity of individuals with HF in the absence of a maximal exercise test. Support: PROPG-UFPE n.23076018672/2020-32; CNPq 421756/2021-7; FACEPE 0801-4.08/21 112236 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Obesitiy and Hypertension in Primary Basic Setting MONICA AMORIM DE OLIVEIRA1, Helena Cramer Veiga Rey1 (1) Instituto Nacional de Cardiologia HTN is the most common, identifiable and modifiable risk factor for cardiovascular disease. The prevalence of SAH is about three times higher in obese patients. Weight loss has an impact on the treatment of HTN and this should be encouraged. The aim of the study was to evaluate the prevalence of obesity in a group of 1000 patients over 18 years of age treated in primary care in the city of Rio de Janeiro and its relationship with HTN. Of the 1014 patients included, 737 (72.68%) were hypertensive. A sedentary lifestyle was present in 65.5% of the population studied and there was no difference between the group of patients with and without SAH. The average BMI of the general population was 29.6 +- 6.2 kg/m2. Being 30.1 +- 6 Kg/m2 and 27.8 +- 6.5 Kg/m2 for hypertensive and non-hypertensive patients, respectively, with statistical significance. Obesity was found in 41.2% of the population studied. The distribution according to the WHO BMI classification can be verified in the table and showing the association between HTN and obesity. The treatment of hypertension in the obese requires a targeted approach to obesity. Adopting a healthy lifestyle facilitates weight loss, increases responsiveness to antihypertensive drug therapy, and produces independent beneficial effects on factors. did not present SAH, as a measure to prevent its development. 112240 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Stereotactic Radiotherapy for the Treatment of Recurrent Refractory VT in Chagas Disease Patients CRISTIANO FARIA PISANI1, Rodrigo M. Kulchetscki1, Bernardo Salvajoli2, Marina P. Mayrink1, Ligia Arteaga2, Jason Cook3, William Stevenson3, Joao Salvajoli2, Mauricio Scanavacca1 (1) InCor - Heart Institute - University of Sao Paulo Medical School; (2) ICESP - Instituto do Cancer do Estado de Sao Paulo; (3) Vanderbilt Heart Background: Stereotactic radiotherapy (SBRT) is a new therapeutic option in cases of recurrent ventricular tachycardia (VT) in patients with structural heart disease where there is a contraindication or a therapeutic failure of the catheter ablation (CA). Objectives: To describe the initial experience of SBRT for recurrent VT in patients with Chagas Cardiomyopathy (CCM) in whom catheter ablation is not an option. Methods: The target sites and SBRT doses were planned based on imaging exams and on bipolar voltage maps from previous CA procedures and new electrophysiologic study was also performed aiming to evaluate the exit site of induced VT. Results: Five patients with CCM and recurrent VT underwent SBRT from July 2021 to April 2022. Most patients were male (60%), mean age 61,4 +- 5, years and EF 22% (Q1: 20 Q3:45). One patient (20%) had two prior catheter ablation and the others only one. The median number of VT episodes in the six and two months prior to SBRT was 13 (Q15.5-Q348.5) and 11 (Q1:2.5;Q3:26.5), respectively. The mean PTV (planning target volume) was 82 +- 17 mL and the ITV (internal target volume) was 29 +- 5 ml, with safe constraints regarding the esophagus and stomach. In a median FU of 194 days, 2 (40%) patients presented VT recurrence. No patients died. The median number of VT episodes reduced from 24 (4.75;52.25) to 2 (0;8.5) (P = 0.068). Conclusion: SBRT is safe and seems to be effective in Chagas Disease patients 112483 Modality: E-Poster Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Remote Blood Pressure Monitoring in Patients with Chronic Heart Failure ANDREY GARANIN1, Andrey Garanin1, Dmitriy Duplyakov1, Irina Mullova1, Oksana Shkaeva1, Polina Duplyakova1 (1) Samara State Medical University Introduction: The pandemic of a new coronavirus infection has shown the need for the development of telemedicine technologies, especially remote medical monitoring using telemonitoring of vital body functions. In some regions, this approach is also justified by the factor of distance and the shortage of certain categories of medical workers. Objective: Decrease of repeated hospitalizations and mortality in patients with chronic heart failure by means of remote monitoring system including arterial pressure monitoring. Methods: 401 patients, who were randomized into two equal groups comparable by sex, age, left ventricular ejection fraction, functional class of heart failure, six-minute walking test results, body mass index, baseline systolic and diastolic blood pressure, and heart rate of the underlying disease and hospitalized for myocardial infarction or decompensation of chronic heart failure, were examined at two research centers. In group 1, remote blood pressure monitoring using oscillometric method was performed using certified tonometers with the ability to transmit the measurement results via cellular communication channel to the research center. Based on the results of the data obtained, the physician was able to contact the patient and adjust the previously prescribed treatment. Group 2 patients performed self-monitoring of blood pressure. All the patients were observed for 3 months. Treatment in both groups was prescribed according to the latest recommendations of the European Society of Cardiology. Results: Group 1 showed a tendency to blood pressure lowering from 130 mmHg to 125 mmHg. In contrast, Group 2 showed an increase in blood pressure from 125 mmHg to 130 mmHg. Group 1 showed 4 hospitalizations related to acute cardiac pathology with a total duration of 30 days; group 2 showed 13 hospitalizations with a total duration of 133 days (p = 0.027; OR; 95% CI 3.4; 1.1-10.8). Total mortality was 6 in group 1 and 11 in group 2 (p = 0.226; OR; 95% CI 1.9; 0.7-5.3). Cardiovascular mortality was 3 in group 1 and 10 in group 2 (p = 0.052; OR; 95% CI 3.5; 0.9-12.9). Conclusions: Remote management of patients with chronic heart failure, including blood pressure monitoring, over 3 months demonstrates a significant reduction in hospitalizations and a trend toward lower total and cardiovascular mortality. 112516 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Beneficial Effects of Aliskiren-Loaded Polymeric Nanoparticles in the Cardiovascular System of Hypertensive Rats OLGA PECHANOVA1, Andrej Barta1, Martina Cebova1 (1) Centre of Experimental Medicine, Slovak Academy of Sciences Background: Aliskiren, a renin inhibitor, has been shown to exert cardio-protective, reno-protective, and anti-atherosclerotic effects independent of its blood pressure lowering activity. However, relatively high dose and frequency of the treatment, which is needed for beneficial effects of the drug, may incur several side effects such as high blood potassium levels, particularly when used with ACE inhibitors in diabetic patients. We hypothesized that gradually released aliskiren from polymer-based nanoparticles could at least partially solve the problem of bioavailability. Therefore, we aimed to determine the effects of aliskiren-loaded polymeric nanoparticles on blood pressure, nitric oxide synthase (NOS) activity and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Methods: Twelve-week-old male spontaneously hypertensive rats were divided into the untreated group, group treated with powdered aliskiren or aliskiren-loaded nanoparticles (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. Blood pressure was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. Results: After 3 weeks, blood pressure was lower in both powdered aliskiren and aliskiren-loaded nanoparticle groups with a more pronounced effect in the latter case. Only aliskiren-loaded nanoparticles increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, aliskiren-loaded nanoparticles decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, aliskiren-loaded nanoparticles represent a promising drug with antihypertensive and cardioprotective effects. 112557 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Randomized Control Trial Comparing Efficiency between Losartan and Amlodipine to Black Hypertensive Cameroonian in Yaounde NGO YOUMBA EP NTEP GWETH1, Marie Ndjie Ndzana1, Liliane Mfeukeu Kuate1, Chris Nadege Nganou Gnindjio1, Valerie Ndobo1, Sylvestre Efonle Ngoh1, Samuel Kingue2 (1) HOPITAL CENTRAL DE YAOUNDE (HCY); (2) HOPITAL GENERAL DE YAOUNDE Randomized control trial comparing efficiency between losartan and amlodipine to hypertensive Cameroonian in Yaounde SUMMARY. Introduction: High blood pressure is the first chronic disease in the world and which also increases the cardiovascular risk. The reduction of this particularly high risk in patients from sub-Saharan Africa should be the main goal of care in our setting. Numerous studies on the choice of a better antihypertensive treatment of arterial hypertension have been conducted but the inherent specificities of our populations, in particular a lower renin activity, a tendency towards sodium-water retention and vascular hyperreactivity, impose a customization of the pharmacological treatment in Africans. Although there is a difference in response to antihypertensive classes in African subjects who respond better to amlodipine than to losartan, few study in our context has yet demonstrated this to the best our knowledge. Objective: The main objective of this study was to compare the efficacy of a amlodipine blocker and losartan receptor blocker in Cameroonian hypertensives at the Yaounde Central Hospital. Methods: This was a randomized, controlled clinical trial phase IV. It involved patients with grade 1 or 2 clinical hypertension, naive to antihypertensive therapy. The intervention consisted in starting the recommended average doses in monotherapy for 12 weeks (84 days) of losartan 50 mg in single dose per day in group 1 and amlodipine 5 mg in single dose per day. Group 2. The follow-up were scheduled 2 weeks. The increase in monotherapy doses occurred from the fourth week (S4) when the blood pressure goal was not reached with losartan 100 mg once a day and amlodipine 10 mg once daily for group 1 and 2, respectively. The patients for whom BP was still not controled despite the increase in monotherapy doses adding a low dose of hydrochlorothiazide at 12.5 mg at eight week (S8) to achieve the blood pressure goal. Compliance assessment was done through Morisky's questionnaire and telephone calls. Results: In all 46 patients initially included, 40 were selected including 21 women and 19 men. The mean age was 54.0 +- 5.5 years in the losartan group 1 and 58.05 +- 7.1 years in the amlodipine group2 (P = 0,350). The two groups were substantially comparable at inclusion for the clinical measurement of blood pressure, the biological parameters tested namely lipid profile, blood ionogram, blood glucose and serum uricemia. After intervention, the mean SBP. 112572 Modality: E-Poster Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY The First Brazilian Cardiovascular Registry of Atrial Fibrillation: The Primary Results of the Recall Study PEDRO GABRIEL MELO DE BARROS E SILVA1, Renato Delascio Lopes1, CR. Hoffmann Filho4, MA. Cavalvante5, C. Miranda6, RB. Esper7, G. Lima8, L. Zimerman9, O. De Souza11, A. Fagundes12, E. Saad10, R. Teixeira12 (1) Brazilian Clinical Research Institute; (2) IP-HCor; (3) Duke Clinical Research Institute, Durham, United States of America; (4) Hospital Regional Hans Dieter Schmidt, Joinville, Brazil; (5) University of the West of Sao Paulo, Presidente Prudente, Brazil; (6) Hospital Madre Teresa, Belo Horizonte, Brazil; (7) Prevent Senior, Sao Paulo, Brazil; (8) Institute of Cardiology of Rio Grande do Sul, Porto Alegre, Brazil; (9) Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; (10) Cardiologia Americas; (11) D'Or Institute for Research and Education, Rio De Janeiro, Brazil; (12) Sociedade Brasileira de Arritmias Cardiacas, Sao Paulo, Brazil There is limited prospective real-world evidence of patients with atrial fibrillation (AF) in Latin America. Methods: RECALL was the first nationwide prospective study of patients in Brazil with known atrial fibrillation. A total of 4,585 patients were included among 89 sites from April 2012 to August 2019. The follow-up was one year by the protocol. Patient characteristics, medications under use and clinical outcomes during the follow-up were collected. Results: From the total of patients enrolled, 41 were excluded from the analysis since they did not have a confirmed diagnosis of AF. The median age was 70 (61-78) years, 46% were women and the majority of the cases were permanent AF (53,8%). The mean CHA2DS2VASc was 3.2 +- 1.6 and the median HASBLED was 2 [2-3]. The most common risk factor was arterial hypertension (77.9%). The median heart rate was 74 [65-85] and the mean ejection fraction was 52.2 +- 2.6 (%). Only 4.4% of patients had history of previous ablation and 30.4% were using anti-arrhythmic. At baseline, 22.0% did not use anticoagulants and 9.1% did not use any antithrombotic therapy. The most common anticoagulant was vitamin K antagonist (VKA) (62.6%) while the remaining 37.4% were direct oral anticoagulants. The main reasons for not using an oral anticoagulant were physician judgment's (low risk of stroke - 24.6%) and difficult to control (14.7%) or perform INR (9.9%) while patient preference and adverse event represented respectively 5.3% and 4.1%, respectively. Only 42.5% of the INRs at baseline were between 2 and 3. During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The use of antithrombotic therapy changed not only during follow-up but it was different also according to the CHADSVASC of the patients. Regarding clinical outcomes in one year, 17.8% of patients were hospitalized due to AF and the rates of death, stroke, systemic embolism and major bleeding were 5.76 [5.12-6.47], 2.77 [2.32-3.32] 1.01 [0.75-1.36], 2.21 [1.81-2.70], respectively. Among VKA users, the rate of mortality and bleeding was higher in the group with time in therapeutic range below 60%. Conclusion: RECALL represents the largest prospective registry of patients with atrial fibrillation in Latin America. Our findings highlight important gaps in the treatment of patients which can inform clinical practice and help to guide future interventions to improve the care of these patients. 112591 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Coronary Artery Bypass Grafting Surgery Improves Frailty at 6-Months Follow-Up: An Insight of the Fragile Clinical Trial OMAR ASRUBAL VILCA MEJIA1, Bianca Meneghini1, Ligia Cristina Fonseca Hoeflinger1, Fabiane Leticia de Freitas1, Bruno Mahler Mioto1, Luis Augusto Ferreira Lisboa1, Luis Alberto de Oliveira Dallan1, Alexandre Chiapina Hueb2, Mauricio Landulfo Jorge Guerrieri2, Rodrigo Coelho Segalote3, Felipe Cosentino3, Fabio Biscegli Jatene1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (2) Hospital das Clinicas Samuel Libanio; (3) Instituto Nacional de Cardiologia do Rio de Janeiro Background: The world is getting older. This change in demographics increases the overall prevalence of coronary artery disease. The growing number of elderlies is not only related to an increase in the number of coronary heart diseases but also frailty, a syndrome that affects at least 10% of the elderly population and is an exceedingly effective parameter for correlating with the adverse effects of aging. Regarding CABG surgery, randomized controlled clinical trials have mainly focused on low-risk, elevated-risk, or high-risk patients, but not on frail patients. Purpose: The aim of this study was to evaluate the impact of coronary artery bypass graft surgery on the frailty index of patients in the 6-month follow-up. Methods: This was a subanalysis of the national, multicenter, randomized, controlled trial called the FRAGILE clinical trial. We analyzed 62 patients aged 60 years or older undergoing coronary artery bypass graft surgery with and without cardiopulmonary bypass in 8 main cardiac surgery centers in Brazil. Fried's Frailty Criteria were used to classify patients into frail, pre-frail, and non-frail. The parameters evaluated were unintentional weight loss, self-reported fatigue, physical activity level, grip strength, and gait speed. We divided the patients into two groups: the off-pump CABG group (n = 30) and the on-pump CABG group (n = 32). We compared each group for frailty variables before and after surgery using the Mann-Whitney test and Stuart-Maxwell marginal homogeneity using the R software. The study was approved by the local Ethics Committee and all patients signed the informed consent. Results: We observed an improvement in the frailty of patients undergoing CABG. Overall, the number of pre-frail patients doubled in 6 months after surgery (from 11 to 22 patients), and the number of frail patients decreased from 19 to1 patient. Nine patients included in the study no longer had any degree of frailty after 6 months of surgery. No patient was classified as non-frail preoperatively in both groups because it was one of the exclusion criteria of the study. There is no difference between the groups. Regarding the frailty criteria, all tests showed differences in the pre and post-surgical comparison, except the unintentional weight loss variable. Conclusion: CABG played a role in improving frailty at the 6-months follow-up. Both techniques, on-pump and off-pump CABG, showed similar results when comparing frailty features before and after CABG surge. 113890 Modality: E-Poster Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Apixaban for Prophylaxis of Thromboembolic Outcomes in COVID-19 - the Primary Results of the Apollo Randomized Trial RENATO DELASCIO LOPES1, Pedro Gabriel Melo de Barros e Silva2, Ariane Vieira Scarlatelli Macedo2, Alexandre B. Cavalcanti4, Regis G. Rosa6, Otavio Berwanger7, Viviane C. Veiga8, Luciano C.P. Azevedo9, Murillo O. Antunes10, Otavio Celso Eluf Gebara11, Eduardo Ramacciotti1, Alvaro Avezum12 (1) Brazilian Clinical Research Institute, Sao Paulo, Brazil; (2) Duke University Medical Center, Durham, NC, USA; (3) Hospital Samaritano Paulista, Sao Paulo, Brazil; (4) HCOR Research Institute, Sao Paulo, Brazil; (5) Brazilian Research in Intensive Care Network; (6) Hospital Moinhos de Vento, Porto Alegre; (7) Academic Resaearch Organization (ARO) - Hospital Israelita Albert Einstein; (8) BP-A Beneficencia Portuguesa de Sao Paulo; (9) Hospital Sirio Libanes Research and Education Institute; (10) Hospital Universitario Sao Francisco de Assis na Providencia de Deus and Irmandade do Senhor Bom Jesus dos Passos da Santa Casa de Misericorida de Braganca Paulista, Braganca Paulista; (11) Dasa-Hospital Santa Paula, Sao Paulo, Brazil; (12) International Research Center, Hospital Alemao Oswaldo Cruz The efficacy and safety of anticoagulation in the early phase of COVID-19 is unknown. Methods: APOLLO is an academic-led, multicenter, randomized, double-blinded clinical trial that planned to enroll 1000 patients from 30 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with onset symptoms up to 10 days at increased risk for thrombotic complications were randomized to apixaban (2.5 mg twice daily) or placebo for 30 days. The primary outcome was the number of days alive and out of the hospital at 30 days. Secondary outcomes included hospitalization for bleeding (key safety outcome), hospitalization for cardiovascular/pulmonary causes (key secondary efficacy outcome). Results: The trial was stopped prematurely due to slower than expected recruitment and low overall event rates. Among 411 (41% of the initial sample size) patients randomized (207 in apixaban and 204 in the placebo group), the mean (+/- SD) age was 44.0 years (+-14.0), 58.4% were women, three patients from the apixaban group withdrew the informed consent, and all the remaining 408 patients completed the 30-day follow-up. The mean time (+/- SD) from symptom onset to randomization was 6.2 (2.4) days. There was no significant difference in the number of days alive and out of the hospital in patients assigned to apixaban and placebo (29.6 +- 1.6 and 29.5 +- 2.4 days, respectively; mean difference 0.18, 95% confidence interval [CI] -0.22 to 0.58; P = 0.38). Among patients assigned to apixaban versus placebo, there was also no significant difference in secondary endpoints including all-cause hospitalization (4.9% vs. 6.9%; odds ratio [OR] 0.70, 95% CI 0.30-1.61), and hospitalization for cardiovascular/pulmonary causes (4.4% vs. 6.9%; odds ratio [OR] 0.63, 95% CI 0.26-1.48). There was no hospitalization due to bleeding and no arterial and venous thrombosis in either study groups. One patient died (in the placebo group) due to a non-cardiovascular cause. Conclusions: In symptomatic, but clinically stable outpatients with COVID-19 and additional risk factors for thrombotic complication, treatment with apixaban 2.5 mg twice daily compared with placebo did not improve the number of days alive and out of the hospital. No major bleeding was observed in the trial population. While the power is limited due to not reaching the intended sample size, our results do not support the routine use of low dose apixaban for outpatients COVID-19. 113909 Modality: E-Poster Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Risk of New-Onset Stroke in Patients with Type 2 Diabetes on Sodium-Glucose Co-Transporter-2 Inhibitor User: A Population-Based Cohort Study GWO-PING JONG1 (1) Chung Shan Medical University Hospital; (2) Chung Shan Medical University; (3) Taoyuan Armed Forces General Hospital; (4) National Defense Medical Center; (5) Central Taiwan University of Science and Technology; (6) Taichung Armed Forces General Hospital Background: Epidemiological evidence suggests the association of diabetes with an increased risk of stroke. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on new-onset stroke (NOS), but the results are inconsistent. Objectives: To determine the association between the use of SGLT2 inhibitors and NOS in patients with type 2 diabetes mellitus (DM). Methods: We conducted a nationwide retrospective cohort study based on the Taiwan Health Insurance Review and Assessment Service database (2016-2019). The primary outcome of the assessment was the risk of incident stroke by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was applied to estimate the adjusted HR of NOS. Subgroup analysis was also conducted. Results: Among the 232,101 eligible patients with type 2 DM aged >=20 years, SGLT2-inhibitor users were compared with non-SGLT2-inhibitor users based on age, sex, and the duration of type 2 DM matching at a ratio of 1:2. The event rate per 10 000 person-months was 9.20 (95% CI 8.95 to 9.45) for SGLT2-inhibitor users and 10.5(10.3-10.6) for non-SGLT2-inhibitor users. There was a decreased risk of NOS for SGLT2-inhibitor users (adjusted HR 0.85, 95% CI 0.82-0.88) compared with non-SGLT2-inhibitor users. Results for the propensity score-matched analyses showed similar results (adjusted HR 0.87, 95% CI 0.84-0.91 for both SGLT2-inhibitor users and non-SGLT2-inhibitor users). Conclusion: The risk of developing NOS was lower in patients with SGLT2-inhibitor users than in non-SGLT2-inhibitor users. The decreased risk of NOS in patients with type 2 DM was greater among patients with concurrent use of statins, biguanides, thiazolidinediones, and glucagon-like peptide-1 receptor agonists. We, therefore, suggest that the long-term use of SGLT2 inhibitors may help reduce the incidence of NOS in patients with type 2 DM. 107880 Modality: E-Poster Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality in a 3-Year Follow-Up of Congestive Heart Failure Due to Chagas Disease in Women and Men ANTONIO DE PADUA MANSUR1, Carlos Henrique Del Carlo1, Jose Antonio Ramos Neto1, Andre Barbosa de Abreu1, Airton Roberto Scipioni1, Antonio Carlos Pereira Barreto1 (1) Insituto do Coracao - HC FMUSP Background: Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of congestive heart failure (CHF) in Latin America and carries a high morbidity and mortality burden. Previously, it was believed that there was no epidemiological and clinical evidence of a gender-associated risk of death in patients with CCC. Purpose: To analyze the mortality of congestive heart failure due to CCC in women and men. Methods: From February 2017 to September 2020, we followed a cohort of patients with CHF (Framingham criteria) due to CCC in a single-center outpatient clinic. Appropriate serologic tests defined Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed with the Kaplan-Meier (K-M) method to analyze time-to-event data and the Cox proportional hazards methods to search for predictors of death. Results: We studied 733 patients, mean of 61.4 +- 12.3 years, 381 (52%) males. Females were older (63.0 +- 11.9 vs. 60 +- 12.4 years; p = 0.01), had a higher baseline mean left ventricular ejection fraction (LVEF) (44.5 +- 14.6% vs. 37.3 +- 14.8%; p < 0.001), and a lower left ventricular diastolic diameter (LVDD) (56.7 +- 8.9 vs. 62.4 +- 9.4 mm; p < 0.001). Over a 3-years follow-up period, 168 (44%) men and 126 (36%) women died . Women had more implantable pacemakers (PM) (26.1% vs. 16.5%; p = 0.002) and men more implantable cardioverter-defibrillators (ICDs)(20.7% vs. 12.5%; p = 0.003). Heart transplant occurred in 10.8% of men and 7.4% in women (p = NS). Cox regression for death adjusted for age, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation, PM, ICD, heart transplant and LVEF, showed, in descending order, previous stroke (HR = 2.4; 95%CL:1.5-3.6), diabetes (HR = 2.0; 95%CL: 1.3-3.1), and CKD (HR = 1.8; 95%CL:1.3-2.6) as the main predictors of death in men, and in women diabetes (HR = 2.2; 95%CL:1.4-3.4), previous stroke (HR = 1.8; 95%CL:1.1-2.9), and CKD (HR = 1.7; 95%CL:1.1-2.7). Conclusions: Women had a better prognosis than men but similar predictors of death. Control of diabetes and prevention of stroke and CKD could significantly reduce the death rate in CHF due to CCC. 107731 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Two Unusual Treatment of Type III Coronary Perforation with Manufacture Coated Stents According to the Reality of a Public Hospital in Brazil. Report of Two Cases FREDERICO LOPES DE OLIVEIRA1, Giulliano Gardenghi2, Adriano Goncalves de Araujo1, Mauricio Lopes Prudente2, Flavio Passos Barbosa1 (1) Hospital de Urgencias Governador Otavio Lage; (2) Hospital Encore; (3) Hospital Samaritano de Goiania Introduction: Coronary perforation is a potentially fatal complication during percutaneous coronary intervention. Although rare (0.2 to 0.6% of procedures), it is life-threatening, which justifies its immediate diagnosis and correction. Objective: We report two cases of coronary perforation and alternative management of current practice. Case reports: CTO 78 years old, admitted on 04/16/2020 and WlSO, 61 years old on 01/12/22, men with previous AMI of more than 12 hours of evolution (CTO with 36 hours and WISO with 18 hours), still in typica pain refractory to intravenous nitrate, dual product control and potent analgesia, thus opting for invasive stratification in both cases. After anterior descending recanalization, a type III rupture with the presence of pericardial contrast was observed. Heparin action was immediately reversed, the balloon was inflated with low pressure and the echocardiography and cardiac surgery teams were contacted. Manufactured coated stents were made (CTO with balloon catheter segment and WISO with a sterile adhesive skin dressing) successfully correcting its perforations. Discussion: In coronary perforation, reversal of anticoagulation and occlusion of the bleeding orifice are essential to prevent tamponade until definitive treatment (lately only direct suture of the vessel by open thoracotomy). However, with the evolution of materials and techniques, it has been proven that ballooning at low pressures and protamine infusion have high success rates in punctual occlusions. Circulatory assist devices and decompressive pericardiocentesis (Marfan puncture) are still needed, increasing costs, morbidity and mortality. In case of failure, polymerized mesh stents (Graft stent) are able to "seal" the leak to pericardial sack, however, their value is high and their numbering is restricted. Thus, alternatives manufactured stents with venous grafts, parts of coronary balloon catheters, sterile skin patches (such as Tegaderm(r)) or even intentional infusion/embolization of autologous fat are good examples of low cost. Other techniques that are also costly, such as the use of microcatheters for infusion of "coils" and the implantation of successive smaller-caliber stents (decreasing the lateral holes), are also used. Conclusion: In the cases reported here, the procedures presented were able to contain the bleeding. We understand that disseminating this knowledge, we can contribute with other colleagues in solving this complication. 107875 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Pediatric Cardiac Myxoma in Carney Report NATHALIE JEANNE MAGIOLI BRAVO-VALENZUELA1, Eliane Lucas4, Juliane R Sousa2, Fernanda C Lemos3, Patricia S Correia2 (1) Curso de Pos-Graduacao em da Sociedade Brasileira de Cardiologia, Instituto Nacional de Cardiologia e Instituto Nacional do Cancer, Rio de Janeiro, RJ, Brasil; (2) Hospital Federal de Bonsucesso (HFB), Rio de Janeiro-RJ, Brazil; (3) Federal University of Rio de Janeiro, Rio de Janeiro-RJ, Brazil; (4) Faculdade de Medicina do Centro Educacional Serra dos Orgaos (UNIFESO), Teresopolis-RJ, Brazil Introduction: Cardiac myxomas are the most common primary cardiac tumors in adults but rare in children. However, in Carney syndrome, myxomas develop at an earlier age and tend to recur more frequently. SC is considered a familial multiple endocrine neoplasia (such as primary adrenal nodular disease, cardiac and cutaneous myxoma, testicular neoplasia) that results from PRKAR1A gene mutations. Case report: We present the case of a 14-year-old male patient who was admitted to our hospital for exercise-induced fatigue, acute chest pain, and mental confusion. His mother reported a history of high blood pressure since the age of 5 that worsened in the last 2 months. His maternal family history was positive for atrial myxoma. A physical examination revealed skin hyperpigmentation, obesity, and hirsutism. Chest radiographic and electrocardiographic findings were normal. Fundoscopy revealed grade II hypertensive retinopathy. Elevated serum ACTH levels were consistent with primary hypercortisolism. The transthoracic echocardiography showed the image of a single, hyperechoic, and irregular mass located in the left atrium . The mass was voluminous, pedunculated, and adhered to the anterior leaflet of the mitral valve, causing obstruction of the left ventricular inlet blood flow. Surgical resection of the tumor was performed, and the histopathological features confirmed the diagnosis of myxoma. Screening for Carney complex was performed. Testicular ultrasonography and abdominal tomography revealed testicular microcalcifications and adrenal tumors, respectively. The patient underwent an uneventful adrenalectomy and was discharged from the hospital on corticosteroid therapy. PRKAR1A gene sequencing showed heterozygosity for the nonsense variant R228X in the patient and his mother. Conclusion: Atrial myxoma justifies surgical resection due to the risk of cardiovascular embolization, complications, and sudden death. Pediatric cardiac myxomas should raise the suspicion of a Carney complex. The early diagnosis of this syndrome contributes to the optimization of the treatment of these patients and can have a positive impact on their management and prognosis. 107905 Modality: E-Poster Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Focal Myocarditis Simulating ST-Segment Elevation Myocardial Infarction in Patients with Berger's Disease ANTONIO TANAJURA GOMES NETO1, Bruna Aparecida Souza Machado1 (1) Clinica Medica Santa Helena - CMSH Introduction: The clinical presentation of myocarditis is variable and often mimics myocardial infarction. The diagnosis of acute myocarditis is frequently empirical and is made based on clinical presentation, electrocardiographic alterations, elevated cardiac enzymes, and theabsence of epicardial coronary artery disease. We report the case of a 46-year-old patient with a history of IgA nephropathy (NIgA) admitted for atypical acute precordial pain associated with ST-segment elevation in the inferiorwall lead. Description: A 46-year-old man with a history of NIgA, SAH, PLD, obesity (BMI 34) and sedentary, using anlodipino/losartan (2.5 mg/50 mg daily), succinato de metoprolol (50 mg daily) and simvastatin (20 mg daily). He was a non smoking and had no family history of coronary heart disease. The patient complained of chest pain into his right hemithorax over the 2 days, stabbing, intermittent, of moderate intensity that traveled into his sternum and right shoulder. The patient looked anxious and high blood pressure (200 x 100 mmHg). His vital signs were stable. Performed ECG and measurement of myocardial necrosis markers (MNM). He was classified as MNM and after improvement he was discharged in a reasonably good condition. ECG: showed ST-segment elevation in the inferior wall. Lab: Hb/Ht: 16/54 U: 35 Cr: 1.39 CKMB: 12 U/L (VR <5 U/L) Troponin: 13 ng/ml (VR: Between 0 and 0.5 ng/ml) Proteinuria 4,488.96 mg/24h Urine volume 1,120 ml Negative thrombophilia investigations. Echo TT: Preserved global and segmental LV systolic function, LV concentric remodeling, and type I diastolic dysfunction. Cate: Myocardial bridge with mild systolic constriction. Cardiovascular magnetic resonance (CMR): Presence of late mesocardial enhancement (non-ischemic pattern) in the inferior basal and inferolateral segments of the left ventricle. ID: Myocarditis. Conclusion: When we came across such a case, some questions were raised, suchas the attempt to correlate myocarditis with the nephrotic picture. The reported case and publications raised bring to light the discussionon the importance of CMR in the diagnosis of acute myocarditis. 108022 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 Vaccine-Induced Myocarditis: Case Report VICTOR RODRIGUES RIBEIRO FERREIRA1, Amanda Pupim Assuncao Toledo1, Maria Fernanda Aguilar de Azevedo2, Maria Christiane Valeria Braga Braile Sternieri1 (1) Braile Cardio; (2) Beneficencia Portuguesa de Sao Jose do Rio Preto/SP Introduction: The global race for a safe and effective vaccine against SARS-CoV-2 (COVID-19) has challenged scientists around the world. The mRNA-based vaccine was quickly linked to cases of myocarditis. Thus, doubts arose about the evolution of the cases and the therapeutic approach. A descriptive study recently published highlighted 1,626 reports myocarditis among the 192,405,448 individuals vaccinated with mRNA based vaccine and registered in the Vaccine Adverse Event Reporting System. Case Description: SKP, 35 years old, healthy, immunized with a booster dose of the BNT162b2 SARS-CoV2 mRNA vaccine and, after 5 days of administration, developed dyspnea on exertion. Laboratory tests rule out acute COVID-19 infection and elevated NTproBNP (2161 pg/ml) indicated acute heart failure. Echocardiography revealed left ventricular (LV) dilatation, reduction in LE ejection fraction (LVEF = 32%), moderate mitral regurgitation and pulmonary hypertension. The Speckle Tracking study revealed reduced strain rate (-9.6%). Cardiac magnetic resonance imaging confirmed myocarditis, revealing mesocardial late enhancement in several segments, with reduced systolic function and mild pericardial effusion. The standardized treatment was optimized doses of Bisoprolol (10 mg/day), Sacubitril/Valsartan (400 mg/day) and Spironolactone (25 mg/day). There was complete remission of symptoms after 5 weeks of treatment. After 14 weeks, a new echocardiographic study revealed normalization of all previously detected alterations. Conclusions: Writing the history of a disease as it unfolds before our eyes is a challenge for contemporary medicine. Findings are built on everyday experiences and case reports have proved to be valuable in the last two years. Vaccine-induced myocarditis still lacks studies regarding its epidemiology and pathophysiology. But we must stick to reality: vaccination remains the most effective means of combating SARS-CoV2. The data are categorical in affirming the benefits of vaccination for public health and the damage related to this pharmaceutical agent is much lower than the damage caused by viral infection in non-immunized peop. 108531 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Rare Etiology of Heart Failure: Primary Cardiac Angiosarcoma ELIAS ANTONIO YUNES2, Andre Luiz Marins Vera Cruz Porto1, Erika Ferreira de Moura Porto1, Carlos Eduardo Cordeiro Soares1, Wolney de Andrade Martins2 (1) Dr. Beda General Hospital, IMNE group, Campos dos Goytacazes, Rio de Janeiro State, Brazil; (2) Postgraduate Course in Cardiology SBC/INC/INCA, Rio de Janeiro, Rio de Janeiro State, Brazil Introduction: Among neoplastic tumors, secondary implants are 132 times more common than primary cardiac tumors (PCT), which have an incidence of 1.38 cases/100,000. More than 90% of TCPs are benign and only 5% to 6% are malignant. Case Description: Female patient, 24 years old, previously healthy, started progressive dyspnea on exertion 30 days ago. She presented dyspnea with mild exertion, paroxysmal nocturnal dyspnea and lower extremity edema, in addition to intermittent fever spikes. Echocardiogram showed left ventricle with normal dimensions and function, ejection fraction = 69%, large tumor mass occupying almost the entire right atrium (RA). Following the investigation, MRI was requested, which showed an extensive mass with invasion of the RA roof, fixed, heterogeneous, irregular, filling almost the entire cavity, extending to the hepatic and superior vena cava, measuring 106 x 100 x 76 mm. A CT-guided biopsy was performed and the histopathological report indicated partially necrotic tissue fragments with proliferation of pleomorphic epithelioid cells forming slits and vascular channels, which associated with positive immunohistochemistry for CD31 and CD34, led to the diagnosis of angiosarcoma. The tumor was considered unresectable and the proposed conduct was chemotherapy with paclitaxel alone for 21/21 days. Staging with chest, abdomen and pelvis CT also showed bone metastasis in the thoracolumbar spine and hip, in addition to mediastinal invasion. After 2 months, she presented a spontaneous femur fracture. She underwent 7 cycles of chemotherapy and died 10 months after the onset of symptoms due to pulmonary sepsis. Conclusion: This report presents a rare case of malignant PCT in a patient with unusual sex and age group, initial clinical presentation with heart failure, extremely aggressive and with a poor prognosis. The increase in PCT diagnoses is attributed to the advances in imaging technology and the use of multimodality. In malignant PCT, sarcomas represent 64.8%, of which 2/3 are angiosarcomas. It most often affects male patients in the fourth decade of life, and in 75% the RA. They can have important hemodynamic and arrhythmic consequences, depending on their size and location. Despite advances in diagnostic methods and cancer treatment, in case of these tumors there are serious limitations. The median survival at 12 months is 45%, but in cases without resection, it drops to 3.8 months. 108362 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Approach to Kounis Syndrome in Coronary Cineangiography FERNANDA CRISTINA CASTANHO1, Claudia Catelan Carlomagno2, Glaucia de Farias Correia2 (1) Hospital Regional de Sorocaba "Dr. Adib Domingos Jatene"; (2) Curso Intensivo de Cardiologia Clinica Introduction: Kounis syndrome is characterized by the coexistence of cardiac signs and symptoms with allergic clinical manifestations. The pathophysiological mechanism involved is believed to include mast cell activation with release of inflammatory mediators that induce coronary vasospasm and/or rupture of the atheromatous plaque. Among the molecules involved, several cytokines and chemokines, histamine, arachidonic acid products, platelet activating factor, neutral proteases, tryptase and cathepsin-D can be identified. Cardiac clinical manifestations differ depending on the syndrome subtype: type 1 results from coronary spasm in normal coronary arteries; type 2, by spasm or rupture of plaque, in coronary arteries with previous atherosclerosis; type 3, the hypersensitivity reaction leads to previously implanted drug-eluting stent thrombosis. Case report: LFS, 67 years old, male, hypertensive, after contrast injection during coronary angiography, evolved with dyspnea, chest pain, hypertension, skin rash and diffuse coronary spasm. Intracoronary injection of nitroglycerin and intravenous injection of hydrocortisone and diphenhydramine were performed with clinical improvement and resolution of pain. Control coronary angiography demonstrating resolution of the spasm without fixed strictures. After clinical stabilization and initiation of drug therapy with diltiazem, he was discharged asymptomatic and without skin changes. Discussion/Conclusion: Among several proposed mechanisms of immediate hypersensitivity to iodinated contrast, the following stand out: direct effect on the membrane related to osmolarity or chemical structure of the iodinated contrast medium molecule; complement system activation; direct bradykinin formation and IgE-mediated mechanism. In the face of sudden chest pain associated with symptoms of allergy or anaphylaxis, the possibility of Kounis syndrome should always be considered. The approach to the patient must be directed to the coronary event and the allergic reaction that induces it. Vasospasm is the primary mechanism, nitrates and calcium channel blockers should be considered first-line therapy. Corticosteroids play an important role in the treatment of allergic reactions and adrenaline is the mainstay of anaphylaxis treatment, however, it can worsen ischemia. Kounis Syndrome is not uncommon, but it is underdiagnosed and there are no specific clinical guidelines for treatment. 108516 Modality: E-Poster Researcher - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY R Over T Phenomenon During Vagal Maneuver THIAGO ALEXANDRE FERREIRA PIRES1, LUDMILLA DA ROCHA FREITAS VIEITAS1, HUGO ANDRADE SANTOS1, BRUNO SANTANA BANDEIRA1 (1) HOSPITAL CAXIAS D'OR Introduction: Supraventricular tachyarrhythmias are frequent pathologies in the emergency department and their approach must be systematized and prepared for possible complications. Degeneration of ventricular rhythms is uncommon but potentially serious. Case description: Young patient, without comorbidities, comes to the emergency room with tachycardic palpitations for 30 minutes. Physical examination showed no changes, BP 120 x 80 mmHg. ECG showing regular, narrow QRS tachycardia with a heart rate of approximately 250 bpm. Corrected normal QT interval. A modified Valsalva maneuver was performed, evolving with a brief period of wide QRS polymorphic tachycardia, with subsequent reversion to sinus rhythm with normal QT interval. Normal laboratory tests. Conclusions: Polymorphic ventricular tachycardia (PVT) is rare, with various causes classified according to the QT interval. In the case of prolonged QT, we have the Torsade of bridges. In cases where the QT is normal, a ventricular extrasystole (VES) with a short coupling interval, which is not pause-dependent, causes PVT. In the case in question, the patient had a narrow QRS tachyarrhythmia, suggestive of tachycardia due to nodal reentry, with hemodynamic stability, and the vagal maneuver was chosen as the initial approach. Evolved with PVT with spontaneous reversion to sinus rhythm. PVT started from a ventricular extrasystole that appeared at the end of the T wave, giving rise to the R over T phenomenon. This is an event that can occur in the VES, when it appears in the T wave of the anterior QRS, generating a conduction with a high probability of developing ventricular tachycardia/fibrillation belonging to grade 5 of the Lown classification. This is an unusual event that can occur during an attempt to reverse arrhythmias. 108522 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR SURGERY Bacterial Endocarditis Due to Coronary Fistula: Case Report LARISSA NETO ESPINDOLA1, Christian Martins Macedo2, Beatriz Sant'ana Isaias Rodrigues1, Elise Sant'ana Isaias1, Paula Oliveira de Andrade Lopes1 (1) Curso Intensivo de Revisao em Cardiologia Clinica; (2) Hospital Santa Izabel Introduction: Coronary fistulas are rare conditions (0.002% of the population), comprising 48.7% of all coronary anomalies. The pathophysiology and clinical presentation depend on the magnitude of the flow through the fistula and its location. They can cause angina (3-7%), dyspnea (60%), endocarditis (20%, usually associated with Streptococcus viridans), syncope, palpitations, congestive heart failure (HF -19%) and cardiac arrhythmias. They can lead to aneurysmal dilatation of the involved coronary artery. Case report: A 46-year-old male patient suffered trauma to the elbow in May/2018, with local phlogosis and recurrent episodes of fever. In September/2018, he had atypical chest pain and increased fever frequency. He sought medical attention and, after auscultation of a heart murmur, a transthoracic echocardiogram (ECHO) was performed, which showed left ventricular dysfunction and severe aortic insufficiency. Therapeutic treatment for HF was initiated, it evolved with significant decompensation, requiring hospitalization. He was discharged on a surgical schedule for valve replacement. He was referred for preoperative cardiac catheterization, which revealed a circumflex artery (CX) aneurysm with a fistula to the right atrium (RA). Transesophageal ECHO showed significant aortic insufficiency secondary to endocarditis and CX fistula to the superior vena cava (SVC). Coronary computed tomography angiography confirmed atrial branch of the CX with fistula to RAand SVC. Negative blood cultures. Patient used Gentamicin + Ceftriaxone. He underwent aortic valve replacement (biological) and ligation of the fistula drainage ostium in the SVC and the proximal ostium next to the CX. Blood transfusion and vasoactive amines was performed in the immediate postoperative period. Conclusion: Coronary angiography is the main diagnostic method. In some cases the origin and relationship of the fistula to adjacent structures can be difficult to determine and non-invasive techniques can be used. There is general agreement that symptomatic patients should be treated. Closure of fistulas in the proximal segment of the coronary vessel is highly recommended due to the greater propensity for aneurysm and rupture. The prognosis of treated patients is excellent, although it depends on the severity of the shunt and on complications such as HF, pulmonary hypertension and bacterial endocarditis. Recurrence rates after surgical treatment are around 25%. Long-term follow-up is essential due to the possibilit. 108530 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Native Aortic Valve Infective Endocarditis with Interventricular Septum Dissection: A Case Report LARISSA NETO ESPINDOLA1, Christian Martins Macedo2, Elise Sant'ana Isaias1, Beatriz Sant'ana Isaias Rodrigues1 (1) Curso Intensivo de Revisao em Cardiologia Clinica; (2) Hospital Santa Izabel Introduction: The global impact of the disease due to infective endocarditis (IE) is practically unknown. IE is a heterogeneous syndrome whose incidence is influenced by multiple factors of the patient himself that determine the risk of infection, including anatomical conditions, injection drug use, in addition to social factors. Case Description: Male patient, 17 years old, using an orthodontic appliance for 1 year, sought the Emergency Unit due to asthenia with 9 months of evolution. Bradycardial, electrocardiogram showing total atrioventricular block (TAVB) and transthoracic echocardiogram (TTE) with signs of right coronary sinus rupture and interventricular septum dissection (IVS). Transesophageal Echo also showed bidirectional flow in the neocavity that formed within the IVS with the presence of perfusion (use of echocardiographic contrast). Vegetation was not seen. Physical examination without peripheral IE stigmata. Antibiotic therapy was started for IE, although blood cultures were negative (patient with dental abscess and visit to a "practical" dentist for braces implantation). Surgical treatment was chosen to close the IVS and excision of possible infected material. During the procedure, an aspect suggestive of a chronic process was observed, with a cavity within the IVS already endothelialized. Opted to occlude entry orifice and reapproximate IVS walls. Definitive pacemaker was implanted (patient on TAVB and with extensive septal lesion). Patient kept under antibiotic therapy for 28 days, when he was discharged in good condition and asymptomatic, after a new TTE confirmed the absence of flow in the topography of the neocavity observed in the preoperative examination. Conclusion: The clinical presentation of IE encompasses a wide spectrum of symptoms, being influenced by multiple factors (pathogen virulence, persistence of bacteremia, extent of tissue destruction (valvular and perivalvular), hemodynamic sequelae, septic embolization, consequences of circulating immune complexes. Due to the close proximity between the atrioventricular node and the proximal intraventricular conduction system and the aortic valve and root, perivalvular extension of infection in this valve is the most common cause of new atrioventricular block of any degree. driving is also a multivariate risk predictor of death associated with IE. 109857 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR IMAGING Huge Atrial Myxoma in an Asymptomatic Patient JULYANA GALVAO TABOSA DO EGITO1, 2. Rafael de Almeida Torres1, 3. Manoela Falsoni1, 4. Remulo Jose Rauen Jr1, 5. Guilherme Barreto Gameiro Silva1 (1) Hospital Santa Cruz - Curitiba - Primary cardiac tumors are rare, and about 75% are benign. Myxoma is the most frequent primary cardiac tumor and its most common location is in the left atrium (LA) (75%). Approximately 70% of patients with LA myxoma have cardiac symptoms. The most frequent symptom is dyspnea (70%). The size, location and mobility of the myxoma will determine the symptomatology and severity of valve obstruction, 12% of myxomas are completely asymptomatic. Although cardiac myxomas are histologically benign, they may be lethal because of their strategic position. Therefore surgical removal should be performed as soon as possible. Case report: Female patient, 53 years old, previously dyslipidemic and with a positive family history of coronary artery disease. She was asymptomatic when she underwent a chest tomography due to the diagnosis of covid-19. The exam resulted in increase in the dimensions of the LA and a voluminous hypodense formation. Physical examination showed telediastolic murmur +/4+. A transesophageal echocardiogram described: Echogenic mass occupying the entire atrial cavity measuring 62 x 46.2, suggestive of myxoma. Preoperative coronary artery CT, showed the size and irrigation of the Myxoma (figure 1). The patient underwent removal of the myxoma without intercurrences. The presence of a murmur in a young and previously healthy patient should not be neglected and it is mandatory to complement it with imaging tests for diagnostic elucidation. 108647 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Subacute Valve Thrombosis After Transcatheter Aortic Valve Replacement in a 86-Year-Old Man with SARS-CoV-2 Infection Successfully Treated with Rivaroxaban JOAO LUIZ DE ALENCAR ARARIPE FALCAO1, Lara Lins Afio Ponte2, Breno de Alencar Araripe Falcao3, Sandra Nivea dos Reis Saraiva Falcao1, Ana Carolina Pereira Nogueira de Alencar Araripe Falcao4 (1) Universidade Federal do Ceara; (2) Universidade de Fortaleza; (3) Hospital de Messejana Dr. Carlos Alberto Studart Gomes; (4) Faculdade Christus Background: Transcatheter aortic valve replacement (TAVR) is indicated for treating symptomatic severe aortic valve stenosis (AS) with intermediate-to-high surgical risks. Few reports are available on managing leaflet thrombosis after TAVR with worsening heart failure. Case Summary: A previously fully vaccinated for SARS-CoV-2 infection 86-year-old man with severe AS received a successful TAVR with Edwards Sapien 3 valve. It was prescribed aspirin 100 mg at hospital discharge. Three weeks later, patient developed flu-like symptoms and fatigue. An RT-PCR test diagnosed SARS-CoV-2 infection. D-dimer test was elevated. Serum creatinine increased to 1.9 mg/dl. A new transthoracic echocardiogram showed a subacute aortic prothesis disfunction with mean transaortic pressure gradient of 50 mmHg. Rivaroxaban 20 mg substituted single antiplatelet therapy to treat presumed subacute leaflet thrombosis. After 45 days of anticoagulation a follow-up echocardiogram showed a decrease in mean transaortic valve pressure gradient to 8 mmHg. Symptoms of heart failure has improved gradually. It was planned to mantain anticoagulation for 3 months. Conclusion: A worsening heart failure or an increase in transaortic valve pressure gradient, especially in the early months after TAVR, suggest subacute leaflet thrombosis. SARS-CoV-2 infection may have triggered this thrombotic event. Subacute thrombosis after TAVR can be resolved after using NOAC as in our present case. 108847 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR IMAGING Dysfunction of Metallic Prosthetic Valve in Mitral Position by Native Posterior Leaflet POLYANA EVANGELISTA LIMA1, Jose Verissimo dos Santos Neto1, Fabio Antonio Amando Granja1, Matheus Pereira Barreira1, Alane Mota dos Santos - Santos, AM1 (1) Universidade Federal do Vale do Sao Francisco Introduction: Infective endocarditis (IE) is a serious pathology with a high mortality rate. Early diagnosis is essential, since delayed or inadequate treatment can lead to serious complications. Case Report: A 47-year-old patient with mitral valve prolapse evolving to severe mitral valve insufficiency underwent valve replacement surgery with a metallic prosthesis. Five months later, he presented with progressive dyspnea NYHA III/IV for 1 month associated with fever peak. Transesophageal echocardiogram was performed, showing mobile mass in the ventricular surface, measuring 15 x 18 mm, and dysfunction of the metallic prosthesis with stenosis. He underwent cardiac surgery that revealed maintenance of the posterior cuspid of the mitral valve, inadvertently preserved along with the subvalvar apparatus that obstructed the prosthesis, locking the posterior hemi-disc. Usually, the vegetation of IE is positioned upstream of the valve; in this case, it would be positioned on the atrial side of the mitral prosthesis. Following the new guidelines, other imaging modalities, such as positron emission tomography with 18F-fluorodeoxyglucose and single photon emission computed tomography have gained importance in defining IE. Conclusion: We report one of the presentation forms of early dysfunction of a metallic prosthesis in mitral position. This is a case that would possibly have benefitted from the use of new imaging modalities for diagnostic elucidation. 108883 Modality: E-Poster Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Unilateral Lung Whiteout in a Infant: A Rare Case of Isolated Unilateral Absence of Pulmonary Artery MARILIA PEREIRA2, Livia Camarinha Franco de Menezes2, Flavia Gurgel3, Anna Esther Araujo e Silva2, Ana Flavia Malheiros Torbey1 (1) Universidade Federal Fluminense; (2) Hospital Universitario Antonio Pedro; (3) Hospital Getulio Vargas Filho Introduction: Isolated unilateral absence of the pulmonary artery (UAPA) is a rare congenital malformation, prevalence range from 1 in 200,000 to 1 in 300,000. Clinical presentation is variable, making its diagnosis a challenge. Some patients have no symptoms and others may have heart failure and pulmonary hypertension (PHT). Case description: 1-year-old boy with a history of pneumonia at 2 months of life, presented to the pediatric emergency room with fever, cough and dyspnea. The chest radiograph showed unilateral whiteout of the left lung with hyperinflation of the right lung, and deviation of the mediastinum to the left. The diagnosis of comunitary pneumonia was made and penicillin initiated. Despite the important clinical improvement, the radiographic image remained and the patient was transferred for investigation of sustained pulmonary hypotransparency. At admission the vital signs were HR of 84 bpm, RR of 24 rmp, SatO2: 97%; breath sounds were decreased on the left side. The bronchoscopy was performed and showed reduction in the caliber of the division of the left main bronchus, making it difficult to visualize the subsegments, and a pulsation in the inferior right third of the trachea without any obstruction. The Doppler echocardiogram revealed a structurally normal heart with a right aortic arch and no visualization of the left pulmonary artery. CT angiography confirmed the absence of the left pulmonary artery. Conclusion: Isolated UAPA is a very rare congenital malformation and the absence of the left pulmonary artery is twice less frequent than that of the right pulmonary artery. Later age at presentation may result in higher risk of morbidity and mortality. The early diagnosis can prevent the development of PHT, recurrent pulmonary infections and hemoptysis. 108902 Modality: E-Poster Researcher - Case Report Category: PHYSIOTHERAPY Inspiratory Muscle Training in Heart Failure with Preserved Ejection Fraction Patients in a Home-Based Cardiac Rehabilitation Case Report RENATA CRUZEIRO RIBAS1, Sabrina Costa Lima de Andrade1, Jessica Blanco Loures1, Estevao Lanna Figueiredo2 (1) RC Fisioterapia - Reabilitacao Cardiovascular; (2) Instituto Orizonti Introduction: Dyspnea and poor exercise tolerance are frequent in Heart Failure with preserved ejection fraction (HFpEF). Respiratory muscle (RM) weakness is an independent predictor of low ventilator efficiency during exercise and contributes to poor prognosis in this population. Inspiratory Muscle Training (IMT) enhances the benefits to aerobic and peripheral muscle training by improving RM fatigue, exercise tolerance and functional status, increasing quality of life (QoL) and reducing mortality. IMT is recommended as part of a cardiac rehabilitation (CR) programme in HFpEF patients. Case report: An 86 year old hypertensive man with reduced functional status on the setting of Covid-19 pandemic lockdown developed HFpEF, with increasing dyspnea (NYHA's functional class III), peripheral and pulmonary congestion. In sinus rhythm. Ejection fraction 65% and signs of diastolic dysfunction on echocardiogram, elevated NTproBNP. Patient was enrolled in a home-based CR programme for 12 weeks, with 4 sessions/week - 2 supervised and monitored sessions and 2 non-supervised. Medical therapy was optimized (diuretics, espironolactone, empagliflozin, anlodipine, telmisartan). Supervised and monitored sessions included IMT with POWERbreathe (PB)(r), set on 30%-40% of S-index, weekly adjusted, and aerobic associated with muscular resistance exercises. The non-supervised sessions included IMT and muscular resistance exercises. Patient was submitted to functional assessment before starting CR, and after 12 weeks, that included dynamic inspiratory strength (S-index), peak inspiratory flow (PIF) and inspiratory volume measured with K5 PB(r), Incremental Shuttle Walk Test (ISWT) and 30-second sit-to-stand test (STS). Dyspnea and self-perceived exertion were assessed with the modified Borg Scale and QoL by Minnesota Living with HF Questionnaire (MLwHFQ). Results: Compared to baseline, there was an increase in the % of the predicted S-index (D55%), in PIF (D2.39%), in inspiratory volume (D0.28%), in ISWT (D200 m) and in STS (D7 repetitions), with reduction in self perceived exertion (very hard to quite hard). There was an important decrease in MLwHFQ (D36 points) related to a better perception of QoL. NYHA's functional class improved and NTproBNP decreased significantly. Conclusion: IMT in CR context, associated with optimized medical therapy, contributed to functional improvements, reducing dyspnea, and amelliorating QoL. This case illustrates how CR can change patient's prognosis. 108931 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Multisystem Inflammatory Syndrome (MIS-C) by SARS VOC-2 and Chikungunya Associated with Left Ventricular Dysfunction - Case Report FIRMINO HAAG FERREIRA JUNIOR1, Camila Louro Mota Branco1 (1) Hospital Geral de Sao Mateus Objective: To describe a case of Multisystem Inflammatory Syndrome (MIS-C) associated with SARS COV-2 and Chicungunya associated with left ventricular dysfunction in a child admitted to a children's intensive care unit in a public hospital in the city of Sao Paulo. Case report: A.S.P.S., female, mixed race, 9 years old, was admitted to the pediatric intensive care unit with fever, dysuria, recent-onset arthralgia, with confluent and hyperchromic micropapular lesions, accompanied by choluria and abdominal pain. On physical examination, she was hypoactive, tachypneic, acyanotic, contacting and oriented. Complete blood count and urine analysis without significant changes. Antibiotic therapy was introduced with Ceftriaxone 2 g/day, Hydrocortisone and clinical support. Serology was requested for SARS COV-2, in addition to serology for Dengue, Chicungunha, Zika and leptospirosis, which showed detectable results for SARS COV-2 and Chicungunha. Abdominal US showing free fluid in the cavity without involvement of target organs. A transthoracic echocardiogram was performed, which showed moderate myocardial dysfunction with associated pericardial effusion without signs of restriction. Opted for the association of pulse therapy with methylprednisolone 10 mg/kg/weight for 3 days, associated with immunoglobulin 1.0 g/kg/weight for 10 days. The control echocardiogram showed preserved ejection fraction, normal cardiac dimensions and mild laminar pericardial effusion. He evolved with progressive improvement of the condition, being discharged asymptomatic and in satisfactory clinical conditions. Conclusion: Multisystem inflammatory syndrome is a rare but serious disease in which children with COVID-19 develop a systemic inflammatory process. Cross-association with other types of viruses is rare, but evident in the literature. Recovery of left ventricular function is very common, and occurs within a few days of starting treatment. The clinical evolution of patients treated early has been favorable, as in the case described above. 108979 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Treatment of Rupture of the Interventricular Septum After Acute Myocardial Infarction: A Possibility MARCELO SABEDOTTI1, Bibiana Guimaraes Maggi1, Leandro Gazziero Rech1, Rafael Massuti1, Rafaela Oliveira Leite2 (1) Hospital Geral de Caxias do Sul; (2) Fundacao Universidade de Caxias do Sul Introduction: Rupture of the interventricular septum (RIVS) is a rare complication of acute myocardial infarction (AMI), which occurrence has decreased due to early intervention of AMI. Despite surgical advances, mortality of RIVS remains high, and such complications may be indicated by a new heart murmur and sudden hemodynamic impairment. Case report: A 70-years-old male with diabetes, dyslipidemia, systemic arterial hypertension, and previous coronary artery bypass surgery, was hospitalized with an acute coronary syndrome without ST-segment elevation. Physical examination demonstrated a holosystolic murmur and diffuse precordial fremitus, with no signs of left heart failure. The patient was stable and promptly referred for early intervention. The coronary angiography demonstrated a subtotal left main coronary artery (LMCA) injury, patent left internal thoracic artery with total occlusion of the anterior descending artery and first diagonal branch. Circumflex artery was dominant, and the first marginal branch had a subtotal injury at the origin and an occlusion of the saphenous graft. Ventriculography demonstrated RIVS on the inferior sept and preserved left ventricular systolic function, with drug-eluting stent implanted on the LMCA towards the circumflex-anterior descending artery, protected by the left internal thoracic artery. The RIVS percutaneous closure was scheduled for the following day. Transthoracic echocardiogram (TTE) identified the RIVS on the lower portion of the muscular sept, with an 11 mm diameter, mild hemodynamic consequences, a 55% Simpson ejection fraction and inferior akinesia. The patient evolved with cardiogenic shock on the day of the procedure, demanding volemic reposition and analgesia. Control TTE demonstrated an increase of the RIVS to 22 mm. We performed the RIVS occlusion as scheduled, through an arteriovenous strap from the right femoral vein to the left femoral artery. The introducer was placed anterogradely through the defect to the ascending aorta. The measurement of the VSD could be performed using a sizing balloon, but due to severe periprocedural instability, we decided on the use of a VSD prosthesis sized according to echocardiographic and angiographic controls. The procedure was successful, with a dramatic hemodynamic improvement after prosthetic placement. The patient was discharged after five days. Conclusion: RIVS percutaneous treatment after AMI is a therapeutic alternative for high-risk surgical patients. 108982 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocarditis and Pulmonary Thromboembolism in a Patient Diagnosed with COVID-19: Case Report CRISTIANE KOPLIN1, Joao Artur Amaral Guarienti2, Felipe Lisboa Frota3, Fabiana Amaral Guarienti4 (1) MD from Federal University of Rio Grande do Sul, Emergency Departament of Public Health Foundation of Novo Hamburgo, Brazil; (2) MD from University of Passo Fundo, Rio Grande do Sul, Brazil; (3) Professional in Physical Education, Physical Activities and Exercises for the Prevention, Treatment of Diseases and Health Promotion Postgraduate Program of Albert Einstein Hospital, Sao Paulo, Brazil; (4) Geriatrics and Gerontology Postgraduate Program of Pontifical Catholic University of Rio Grande do Sul, Brain Institute, Porto Alegre, Brazil Introduction: This report describes the case of a patient diagnosed with COVID-19 who presented with symptoms of myocarditis and pulmonary thromboembolism (PTE). Case description: Female patient, 35 years old, arrived at the emergency in June 2020 with flu-like symptoms. History of allergic rhinitis, asthma, grade II obesity (BMI: 37.2 Kg/m2) and miscarriage in 2017. Requested RT-PCR SARS-CoV-2 with positive result. The patient had a good evolution with symptomatic treatment. She returned after two months with burning chest pain and vomiting. On arrival she was hypertensive (BP: 190/120 mmHg) and the electrocardiogram showed no acute ischemic changes. However, myocardial necrosis markers, troponin T and CK-MB, were positive in three measurements. The case was initially managed as an acute myocardial infarction without ST-segment elevation. Coronary Angiography showed no coronary lesions. The Transthoracic Echocardiogram showed an LV with increased wall thickness (Fig 1). The patient also had increased inflammatory markers (C-Reactive Protein and ESV). Treated with analgesics and antihypertensives, she had an improvement of the symptoms. She was discharged with outpatient follow-up for suspected myocarditis. After three months the patient returned with dyspnea for 3 days. She had 82% O2 saturation on room air, BP 150/110 mmHg and no other findings. Pulmonary artery CT Angiography showed signs of PTE (Fig. 2). As she had a Pulmonary Embolism Severity Index (PESI) of 55, indicating a low risk of severe morbidity, she was released and maintained on oral anticoagulation. Conclusions: The pathophysiology of cardiovascular complications associated with COVID-19 is not completely understood. Myocardial viral infection and cytokine storm are etiological theories. This patient had typical signs of myocarditis with a history of recent viral illness, indicating an important relation between COVID-19 and myocardial damage. The thrombus tendency in COVID-19 may involve two mechanisms: a hypercoagulable state responsible for large vessel thromboembolism and direct endothelial injury responsible for microvascular thrombosis. In this report, PTE may have an etiologic link with previous SARS-CoV-2 disease. Interestingly, the relationship between COVID-19 and cardiovascular complications seems evident. Therefore, there is a need of additional studies to elucidate the pathophysiology of cardiovascular impairment related to COVID-19. 109004 Modality: E-Poster Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Subclavian Vertebro Steal Phenomenon in the Right Vertebral Artery: A Case Report ROMERO HENRIQUE DE ALMEIDA BARBOSA1, Gabriela Santos Andrade1, Nayara Ribeiro Maximo de Almeida1, Poliana kalinne Simoes de Melo Barbosa2, Adirlene Pontes de Oliveira Tenorio1 (1) Universidade Federal do Vale do Sao Francisco; (2) Instituto Medico Sao Francisco Introduction: The subclavian vertebro steal phenomenon(SVSP) occurs when a stenosis or occlusion in the brachioencephalic trunk or subclavian artery proximal to the origin of the vertebral artery causes partial or complete reversal of blood flow from the ipsolateral vertebral artery. It usually behaves asymptomatically, in up to 80% of patients, but may evolve with symptoms of vertebrobasilar insufficiency. Atherosclerotic disease is the most common cause and the left side is more commonly affected in a 4:1 ratio with respect to the right side. Case description: I.M.S., female, 66 years old, Body Mass Index: 26, from Delmiro Gouveia-AL, diabetic, hypertensive, chronic renal failure on dialysis. Due to frequent dizziness and syncope, she had her first medical visit on 07/10/19, denying previous neurological and cardiologic symptoms. After suspension of beta-blockers and hydroelectrolytic and metabolic correction, Holter was requested, which showed advanced atrial ventricular block, being referred for definitive pacemaker implantation. After implantation, she returned for consultation on 24/01/20, hemodynamically stable, but with persistent vertigo. Doppler echocardiography of the carotid and vertebral arteries was requested, which revealed a totally reverse flow in the right vertebral artery, compatible with SVSP with permanente retrograde pattern. A computed tomography angiotomography of the cervical artery and venous was ordered on 01/21/2021, showing a mixed plaque located in the proximal right subclavian artery at the origin of the right vertebral artery, with an irregular surface, determining stenosis between 50 and 70%, with an extension of 2 cm. After evaluation by the vascular surgeon to analyze the need for the procedure, supra-aortic trunk angioplasty was indicated as treatment for SVPS. Conclusions: The SVSP in the right vertebral artery is of infrequent occurrence, about 10% of cases, and that in about 5% of patients present symptoms, the report of this case can contribute to the identification of such condition and differential diagnosis of vertigo and syncope. 109073 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR IMAGING Left Atrial Mixoma: An Unusual Presentation PEDRO ANTONIO GALDEANO1, PATRICIA REGINA ALVES GALDEANO1, GABRIEL ANTONIO STANISCI MIGUEL1, FERNANDA NOGUEIRA BUENO RODRIGUES ALVES1 (1) CLINICORE; (2) CARDIOLIFE Identification: Patient 52 years old, female, white, natural from anapolis-goias. Case report: patient presented in 2014 a complaint of palpitations with effort associated with episode of transient loss of movement in lower left left seeking medical assistance. Requested echocardiogram that demonstrates a large oval image (figure), regular outlines, measuring 03 x 03 cm, inside the left atrium with bulleting to the inside of the left ventricle adhered to the interatrial septum, and the hypothesis of left atrial mixoma being proposed. Patient after clinical stabilization was referred to heart surgery with complete removal and diagnostic confirmation by anatomological and pathological left atrial mixoma. In the year 2021 (07 years after surgery) in control examination with echocardiogram, a regular contour mass was again identified, measuring 07 x 07 mm adhered to the interatrial septum (figure) with probable diagnostic hypothesis of recurrence of left atrial mixoma. Discussion: Cardiac mixoma is the most common primary tumor of the heart and is mainly located in the left atrium. It predominates in the female sex and the age group around 50 years old, being rare in children. Symptomatology depends on the size, shape, mobility and location of the tumor. The treatment is surgical removal, which most of the times is curative. Conclusion: Recurrence of cardiac myxoma after surgical removal is uncommon. This is due to the excision of its implantation base in the heart walls. If this resection is not broad, there is a possibility of the tumor recurrence. In the present case, the patient was followed annually without presenting residual image to echocardiography. Mixoma recurrence in followed cases is uncommon, which aroused the interest of the authors. 109330 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR SURGERY A Rare Mitral Valve Tumor DEINER PAULO MARTINS RESENDE 1, Alberto Rodolpho Huning1, Giuliano Minor Zortea1, Marcia Castilhos Puchalski1, Marcela da Cunha Sales1 (1) Santa Casa de Misericordia de Porto Alegre (ISCMPA) Introduction: Benign intracardiac tumors are uncommon entities, among which blood cysts are even rarer. They are usually located in the heart valves or adjacent structures and have a congenital in origin, disappearing spontaneously with time and rarely found after the first year of life. These tumors can cause left ventricular outflow tract (LVOT) obstruction, valve dysfunction, pulmonary embolism, and coronary obstruction. From 1960 to 2021, only 54 cases of blood cysts located in the mitral valve have been reported. Case report: We present a case of a 36-year-old man, asymptomatic, who sought a cardiologist for routine evaluation. The electrocardiogram was normal. The transthoracic echocardiogram showed a rounded structure, with hyperechogenic edges, hypoechogenic center, measuring 2.1 x 1.9 cm (3,4 cm2), located in the chordae of the anterolateral papillary muscle of the mitral valve, without obstruction of the LVOT. Cardiac magnetic resonance imaging showed a sessile mass attached to the head of the anterolateral papillary muscle, 24 x 20 x 19 mm, hypointense and absence of contrast uptake. The patient was referred for cardiac surgery, where 2 cysts were identified, completely attached to the mitral valve and subvalvular apparatus. Resection of the anterior leaflet, chordae, top of the anterolateral papillary muscle and cysts were performed, followed by implantation of a bioprosthesis. Conclusion: Intracardiac blood cyst are more commom in newborns and extremely rare in adults. Surgery is usually indicated due to the risk of embolization and other potential complications, as well as to define the exact diagnosis. 109566 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Cardiac Involvement as an Early Sign of Hereditary Transthyretin Amyloidosis Manifestation in Carrier of the 107Val Mutation in the TTR Gene: A Case Report ANTONIO AUGUSTO XIMENES2, Carolina The Macedo1, Jemima Araujo Silva Batista4, Marcela Machado Costa6, Tonnison de Oliveira Silva2 (1) Curso de Pos-Graduacao em Cardiologia da SBC/INC/INCA; (2) Hospital Cardio Pulmonar, Rede D'Or; (3) Hospital Sao Rafael, Rede D'Or; (4) Universidade Federal do Vale do Sao Francisco, UNIVASF; (5) Faculdade Estacio de Juazeiro; (6) Escola Bahiana de Medicina e Saude Publica, EBMSP Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe disease transmitted by an autosomal dominant inheritance associated to more than 100 mutations in the transthyretin gene. The ATTRv phenotypic expression depends mainly, but not exclusively, on the type of mutation, with neurological and/or cardiological involvement most frequently. The improvement of the disease prognosis by the new drugs available relies on early diagnosis and treatment. The best strategy for the earliest diagnosis is based on knowledge about how the disease manifests itself in each mutation. However, due to the incomplete penetrance of mutations, detection of an initial stage of the disease is challenging. Val107 (Ile107Val) mutation is a rare form of ATTRv, characterized by neurological and cardiological involvement, with neurological impairment manifesting earlier and being more severe. We describe a case with cardiological alterations as the initial manifestation of the disease. Case: 20/12 Asymptomatic 58-year-old male with Val107 mutation. He is is part of a group of 27 carriers of the Val107 mutation, followed up by our group. The institution protocol for the asymptomatic carriers routinely includes cardiological tests. Normal physical examination. Bilateral carpal tunnel syndrome confirmed by electroneuromyography Protein electrophoresis - no monoclonal band. Echocardiogram (Echo) - Left Ventricular ejection fraction (LVEF) 65%/Global Longitudinal Strain (GLS) = -17%. Holter - rare supra and ventricular ectopy. Cardiac Ressonance - mild pericardial effusion, increased left atrium. 99 mTc-PYP bone scintigraphy - Perugini grade 3 cardiac uptake and H/CL ratio = 1.56. Tafamidis was introduced. 22/03 Echo: LVEF: 70%, GLS:-20%, apical sparing pattern. Conclusion: In the scarce literature available on Val107 ATTRv, the neurological impairment is the most common form of initial manifestation, being cardiac involvement observed later. However, this case points out that cardiological tests should also be included early in the monitoring strategy of asymptomatic Val107 carriers for diagnosis of ATTRv. 111119 Modality: E-Poster Researcher - Case Report Category: HYPERTENSION/RENAL DENERVATION Serious Systemic Arterial Hypertension Secondary to Paraganglioma - Case Report ELIZABETH CARDOSO DOS SANTOS1, Vera Maria Lucia Cury Salemi2, Fernanda Willemann Ungaretti1, Juliana Gil de Moraes1, Roberto Kalil Filho1 (1) Sociedade Beneficente de Senhoras Hospital Sirio Libanes; (2) Instituto do Coracao Paragangliomas are rare tumors originating from cells from the neuroendocrine system, and like pheochromocytoma, they are catecholamine producers. However, they usually differ in their location, which is extra-adrenal. Regarding the clinical presentation, the classic triad consists of episodic headache, palpitations and sweating. Therefore, the objective is to describe an unusual clinical case and the general aspects of this entity. Case report: A 29-year-old man with previous retroviral disease and arrhythmia is admitted to the emergency room with headache and an episode of emesis, with blood pressure levels of 247 x 152 mmHg. He reports episodes of morning headache associated with nausea and palpitations for 3 weeks. He was evaluated by the neurologist, with normal eye fundus and cranial computed tomography, and was hospitalized for blood pressure control and investigation of secondary systemic arterial hypertension. Laboratory tests were performed, the results of which showed significantly increased levels of vanillylmandelic acid, catecholamines and urinary metanephrines, and complementary tests such as: abdominal computed tomography that showed a voluminous solid lesion with necrotic areas and heterogeneous post-contrast enhancement centered on the right adrenal store, measuring approximately 6.5 x 6.0 x 5.0 cm. The mass displaces the inferior vena cava, trunk and posterior right portal branch, without signs of vascular invasion, presents extensive contact with the upper pole of the right kidney, displacing it inferiorly, but maintains a cleavage plane, suggesting the possibility of pheochromocytoma. Abdominal magnetic resonance imaging showed a solid mass in the right adrenal, indeterminate, suggesting that, in addition to pheochromocytoma, we consider carcinoma as a possibility. Whole-body PET-CT showed marked glycolytic hypermetabolism in the right adrenal mass, suspicious for a neoplastic process. He underwent resection of a peritoneal mass, right hepatectomy and partial resection of the inferior vena cava with primary reconstruction. The immunohistochemical profile was compatible with succinate dehydrogenase deficient paraganglioma. After tumor excision, the patient evolved with good blood pressure control and is currently asymptomatic. Discussion: Once there is a clinical suspicion of pheochromocytoma/paraganglioma, laboratory tests and imaging tests should be performed, and surgical removal of the tumor remains the only curative treatment. 109606 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR SURGERY Major Recurrent Ventricular Pseudoaneurysm in a Patient with Behcet MARINA PINHEIRO ROCHA FANTINI1, Juan Mario Vaca Pereira Vrandecic2, Felipe Magalhaes Becker1, Larissa Maria Ferrarez Faria4, Carlos Eduardo de Menezes e Souza Filho5 (1) Hospital Mater Dei; (2) Santa Casa de Belo Horizonte; (3) ECMO MINAS; (4) Faculdade Ciencias Medicas de MG; (5) Faculdade Federal de Minas Gerais Introduction: Behcet Syndrome (BS) is an autoimmune systemic vasculitis of variable caliber and with different phenotypes. It classically courses with ulcerative, papulopustular and nodular erythema-like lesions on the skin, mucous membranes and genital region. Among its presentations, angio-behcet has venous and, rarely, arterial vascular involvement. These arterial presentations, despite affecting approximately 4% of patients, represent a unique characteristic of BS, whose aneurysms potentially affect peripheral, visceral and pulmonary arteries. This case report presents a 16-year-old boy with recurrent left ventricular pseudoaneurysms since 2020. Case Report: ELP, male, 16 years old. He was diagnosed with Behcet's Syndrome in 2020 when he started presenting oral and genital ulcers, constitutional symptoms, hepatosplenomegaly, fever and night sweats. He underwent surgery to correct a left ventricular (LV) pseudoaneurysm on 5/29/20, did not improve and presented an aortic pseudoaneurysm and a new left ventricular apex pseudoaneurysm on examination on 8/28/20. As a result, he started pulse therapy with methylprednisolone and cyclophosphamide on 9/2/20 and surgical correction of ventricular and aortic pseudoaneurysms on 9/8/20. Treatment with pulse therapy was maintained, with 9 sessions with cyclophosphamide, until the finding of a new ventricular pseudoaneurysm on 10/01/21, when the corticosteroid was changed to infliximab. This new pseudoaneurysm had important dimensions (12.1 cm x 7.6 cm in its largest diameters), presence of LV shunt to the pseudoaneurysm, with a peak gradient of 64 mmHg and maximum velocity of 4.01 m/s, ejection fraction of (EF) 62.17% and preserved biventricular systolic function. He was admitted on 01/18/22 with decompensated heart failure with a warm and humid profile, associated with anasarca, EF of 37.5% and LV and right ventricle dysfunction. The conduct was clinical treatment and enrollment for urgent heart transplantation. Conclusion: This report discusses a rare case of recurrent left ventricular aneurysm in a 16-year-old boy, with recurrent cardiac manifestations despite immunosuppressive therapy and corrective surgery. The patient's condition shows that Behcet's Syndrome may present as an aggressive cardiac form with more severe manifestations. 109690 Modality: E-Poster Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Myocardial Revascularization in a Patient with an Anomalous Left Coronary Trunk with a Trajectory Posterior to the Pulmonary Artery and Anterior to the Aorta MARINA PINHEIRO ROCHA FANTINI1, Henrique Loiola Duarte5, Pedro Henrique Cavalcanti de Albuquerque Sa5, Leonardo Nunes Coelho Fantini1, Vinicius Loureiro2 (1) Hospital Mater Dei; (2) Santa Casa de Belo Horizonte; (3) ECMO MINAS; (4) Faculdade Ciencias Medicas de MG; (5) Faculdade Federal de Minas Gerais Introduction: Anomalous coronary artery emerging from the contralateral sinus is a rare congenital anomaly. Some variations incur increased risk of adverse cardiovascular events, with sudden death often being the initial manifestation of the disease. This report presents a case of a patient with a variant of anomalous coronary artery with a poor prognosis, requiring surgical myocardial revascularization. Case Report: SASL, female, 59 years old, diagnosed with anomalous coronary artery in 2014. On that occasion, coronary angiography was performed after the atypical chest pain, which showed an anomalous origin of the left coronary trunk, without atheromatous problems. She also has arterial hypertension, dyslipidemia and hypothyroidism, and uses Olmesartan, Hydrochlorothiazide, Duloxetine, Levothyroxine, Rosuvastatin and Alprazolam. On 01/2022, she had angina pectoris and dyspnea on exertion. She underwent an exercise stress test, which was positive for ischemia. Coronary computed tomography angiography was performed, which showed the left coronary trunk with anomalous origin in the right coronary sinus, path posterior to the pulmonary artery and anterior to the aorta, calcified plaque in the ostium of the anterior descending artery, determining luminal reduction of 25 to 49%. After evaluation, The Heart Team of Hospital Felicio Rocho opted for surgical intervention. She was admitted electively on 03/03/2022 for myocardial revascularization by the construction of a bridge from the mammary artery to the anterior descending artery using cardiopulmonary bypass and under balanced general anesthesia and erector spinae plane block. Extubated while still in the operating room, she was referred to the intensive care unit (ICU) in good clinical condition. She was discharged from the ICU on the 2nd postoperative day (POD) and discharged from the hospital on the 7th POD. The postoperative echocardiogram showed preserved biventricular systolic function, mild aortic insufficiency, laminar pericardial effusion and left ventricular ejection fraction = 71%. She is currently asymptomatic and in outpatient follow-up. Conclusion: This report highlights the situation of a patient with an anomalous coronary trunk who had her cardiovascular prognosis positively modified by means of surgical myocardial revascularization. This demonstrates the importance of diagnostic investigation and surgical intervention in these patients, in order to avoid negative outcomes such as sudden death. 109701 Modality: E-Poster Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Myocardial Revascularization in a Patient with an Anomalous Left Coronary Trunk with a Trajectory Posterior to the Pulmonary Artery and Anterior to the Aorta MARINA PINHEIRO ROCHA FANTINI1, Felipe Becker Magalhaes1, Carlos Eduardo de Menezes e Souza Filho5, Larissa Maria Ferrarez Faria4, Murilo Malta Batista2 (1) Hospital Mater Dei; (2) Santa Casa de Belo Horizonte; (3) ECMO MINAS; (4) Faculdade Ciencias Medicas de MG; (5) Faculdade Federal de Minas Gerais Introduction: Anomalous coronary artery emerging from the contralateral sinus is a rare congenital anomaly. Some variations incur increased risk of adverse cardiovascular events, with sudden death often being the initial manifestation of the disease. This report presents a case of a patient with a variant of anomalous coronary artery with a poor prognosis, requiring surgical myocardial revascularization. Case Report: SASL, female, 59 years old, diagnosed with anomalous coronary artery in 2014. On that occasion, coronary angiography was performed after the atypical chest pain, which showed an anomalous origin of the left coronary trunk, without atheromatous problems. She also has arterial hypertension, dyslipidemia and hypothyroidism, and uses Olmesartan, Hydrochlorothiazide, Duloxetine, Levothyroxine, Rosuvastatin and Alprazolam. On 01/2022, she had angina pectoris and dyspnea on exertion. She underwent an exercise stress test, which was positive for ischemia. Coronary computed tomography angiography was performed, which showed the left coronary trunk with anomalous origin in the right coronary sinus, path posterior to the pulmonary artery and anterior to the aorta, calcified plaque in the ostium of the anterior descending artery, determining luminal reduction of 25 to 49%. After evaluation, The Heart Team of Hospital Felicio Rocho opted for surgical intervention. She was admitted electively on 03/03/2022 for myocardial revascularization by the construction of a bridge from the mammary artery to the anterior descending artery using cardiopulmonary bypass and under balanced general anesthesia and erector spinae plane block. Extubated while still in the operating room, she was referred to the intensive care unit (ICU) in good clinical condition. She was discharged from the ICU on the 2nd postoperative day (POD) and discharged from the hospital on the 7th POD. The postoperative echocardiogram showed preserved biventricular systolic function, mild aortic insufficiency, laminar pericardial effusion and left ventricular ejection fraction = 71%. She is currently asymptomatic and in outpatient follow-up. Conclusion: This report highlights the situation of a patient with an anomalous coronary trunk who had her cardiovascular prognosis positively modified by means of surgical myocardial revascularization. This demonstrates the importance of diagnostic investigation and surgical intervention in these patients, in order to avoid negative outcomes such as sudden death. 109781 Modality: E-Poster Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Myocardial Infarction with Non-Obstructive Coronary Arteries (Minoca): A Case Report of a Young and Athletic Woman FRANCISCO ITALO DUARTE KUMAMOTO 1, Maria Alice Oliveira Magalhaes Teixeira1, Maria Eliza Soares Gadelha de Oliveira1, Eduardo Franco Correia Cruz Filho1, Ana Carolina Navarro Henriques Cabral1 (1) Hospital Memorial Sao Francisco Introduction: Myocardial Infarction With Non-Obstructive Coronary Artery (MINOCA) is a special type of Acute Myocardial Infarction (AMI). It is considered a working diagnosis, because the disease behaves similarly to a conventional AMI until the Coronary CT Angiography is done, which does not show lesions greater than 50% of the lumen in a main epicardial vessel, and this possibility should be considered until no other clinically overt specific cause is proven. Compared to coronary obstruction, It most often affects young women without comorbidities, such as the case reported. Case Report: A 35 year old female, without comorbidities, entered in the ER in 2019 complaining of anginal chest pain, palpitations, intense sweating, drowsiness and high SBP of 180 mmHg. Based on the past medical history, the physical examination was normal and biomarkers were abnormal. A coronary CT Angiography showed an eccentric thrombus in the distal midsegment of the descendant anterior artery, which determined luminal stenosis below 50%. Changes in the left marginal branch, including left ventricle with subendocardic hypoattenuation of the anterior and septal walls of the apical region were also detected. According to the patient, the ECG was abnormal. The transthoracic echocardiogram showed an anterior and apical hypokinesis of the left ventricle. The cardiac catheterization presented an isolated lesion of the descendant anterior artery, which determined luminal stenosis below 50%. She was overtreated with aspirin, captopril, furosemide and low molecular weight heparine and was followed up by a cardiologist over 2 years. She remained asymptomatic until February 2022, when was admitted in the ER, reporting typical anginal pain. The cardiac troponin-1 was abnormal (2.8 ng/ml). She was admitted to the CCU. The electrocardiogram was normal. The coronary CT Angiography did not show any obstructive lesion and the cardiac catheterization was normal. The Magnetic Resonance Imaging (MRI) showed the presence of Late Gadolinium Enhancement (LGE) in subendocardial area, suggesting previous AMI. Today, she was discharged, with aspirine, statin and beta blocker. Conclusion: Young patient without classic cardiovascular risk factors with apical wall AMI confirmed by magnetic resonance imaging without obstructive lesion, which in our view is compatible with MINOCA. 109836 Modality: E-Poster Researcher - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Defibrillator in a Pregnant Woman with Arrhythmogenic Right Ventricular Cardiomyopathy: Concerns About Procedure, Pregnancy and Delivery ERIKA OLIVIER VILELA BRAGANCA1, Erika Olivier Vilela Braganca1, Graziela Oliveira de Avelar1 (1) RitmoCheck Introduction: 35-year-old woman with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) with non-sustained ventricular tachycardia, right ventricular enlargement, left ventricular dysfunction (LVEF 46%) and important cardiac fibrosis (45% of late enhancement in cardiac MRI) and an ICD was indicated to primary prevention. Preoperative tests showed a positive betahCG and obstetric consultation confirm the pregnancy. After sharing making decision against radiation exposure and sudden cardiac death, we decided to move on to procedure of implantation of an ICD. The ionizing radiation is absorbed by any part of the body and the pregnant woman receive protective apron against lead in her belly, neck, head and eyes. The procedure was performed using fluoroscopic view and a dual chamber ICD was implanted. The total time was sixty minutes, the radiation time was ninety seconds and the burden of radiation was 1.6rads and the acute electronic measurements were very good. The post operative period was suitable and no cardiovascular or obstetric complication was noted during the pregnancy. Betablocker has not been discontinued. At 38 weeks the patient went into labor and the route of delivery chosen was the vaginal one. The patient underwent epidural anesthesia and she gave birth a female newborn of 3,315g weight and an Apgar score of 9/10. Only ventricular ectopics beats was seem during this period of time and no device abnormality. The puerperium phase was uneventful. Discussion: There are a few studies of pregnancy with ICD managed and there are actually no guidelines for this issue. As regarding ARVC only sixty pregnancies were identified between 1968 and 2016 and only 17% having an ICD. ARVC is associated with a low rate of major cardiac events and vaginal delivery appears safe. X-ray exposure of less than 5 rads has not been associated with an increased chance for birth defects. Conclusion: The ICD is a relative contraindication during pregnancy, nonetheless the procedure and delivery should be carefully planned and protected. 109823 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Carcinoid Heart Disease and the Best Time for Valve Surgical Approach - Case Report LARISSA ARLETE MOSKO1, Bruna Bozelli Leopoldino Barion1, Michael Malca Sepulveda2, Sanderson Antonio Cauduro1, Celso Soares Nascimento2 (1) Hospital Erasto Gaertner HEG; (2) Hospital Angelina Caron HAC Introduction: Neuroendocrine tumors (NET) are neoplasms derived from enterochromaphin cells that produce neurotransmitters and neuromodulators. Its incidence is 2-5 new cases per 100,000 inhabitants/year. Skin flushing, diarrhea, telangiectasia and cardiac lesions are symptoms that characterize Carcoininoid Syndrom (CS). The Biopsy defines the diagnosis. Cardiac involvement is due to an increase in the right heart caused by tricuspid and pulmonary insufficiency. Valve replacement can improve functional capacity. Case Description: A 50-year-old male patient was admitted in 2017 to oncology hospital Erasto Gaertner with diarrhea, urticariform lesions and 15-kilo weight loss. He denied comorbidities and use of medications Upon examination, palpable mass in the abdomen was noticed. Hepatic nodulus were found on CT scan. A biopsy of these lesions revealed neoplasm of metastatic neuroendocrine pattern. Search for the primary site was carried out unsuccessfully. The initial echocardiogram showed an increase in the right chambers, with preserved right ventricular (RV) systolic function and severe tricuspid insufficiency. Despite the use of somatostatin analogs (SA), in 2018, the patient presented signs of right heart failure, hence a proposal for surgical approach, patient turned it down. Chemoembolization the liver lesions was performed to decrease serotonin hypersecretory. In 2021, he presented cardiac decompensation with RV dysfunction on echocardiogram. Back then, the patient agreed to tricuspid valve replacement, but in post-op even with the use of SA, the decompensation evolved to refractory cardiogenic shock due to RV failure, causing death. Conclusion: The carcinoid heart (CH) is a therapeutic challenge not only regarding risks of valvar surgical intervention, but also because of the systemic effects of CS itself triggered by surgical trauma. NGUYEN et al. evaluated 240 patients who underwent valve surgery. In this study, as well as in other analysis of smaller groups, most of the patients who were assessed received SA in pre and post op, modifying surgical evolution. Furthermore, early surgery improved short and long-term outcomes. In this case report, the patient refused to undergo early valve replacement surgery, and approach with RV dysfunction was performed, which probably contributed to the unfavorable outcome. Patient selection, the care of a multidisciplinary team and SA infusion protocols, seem to be the main points for success in the CH approach. 109832 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR SURGERY Ressection of Infected Thoracic Endograft using Extra-Anatomical By-Pass and Revascularization of Left Carotid EDMILSON CARDOSO DOS SANTOS FILHO1, Diogo Alves Cardoso3, Simone Cristina Soares Brandao1, Manuela de Sousa Moura Fe1, Fabio Antonio Amando Granja1 (1) Hospital das Clinicas da Universidade Federal de Pernambuco; (2) Instituto do Coracao de Pernambuco; (3) Faculdade Pernambucana de Saude Introduction: Thoracic stent graft infections are devastating complications related to the treatment of aortic aneurysms. Definitive treatment requires a strategy of revascularization, explantation of the infected prosthesis, and debridement of all infected tissue. It represents a flaw in the minimally invasive approach to endovascular treatment and puts the patient at an increased risk of morbidity and mortality. Case description: A 42-year-old female patient, HIV + with an undetectable viral load, was admitted complaining of asthenia, cough, and intermittent fever (39-40degC) for 9 days. Hospitalized 6 months earlier due to COVID-19 infection, she evolved with pericardial effusion with purulent cardiac tamponade, and a pericardial window was performed. Had endovascular treatment for a traumatic descending aortic aneurysm 13 years ago. Despite an inconclusive investigation for an infectious focus, the patient initially presented a clinical and laboratory response to empirical ABX (cefepime + teicoplanin). After 10 days of treatment, she returned to present febrile peaks associated with an increase in WBC and CRP. PET-CT showed increased uptake and periprosthetic gas, suggesting infection with the presence of biofilm. The surgical approach was performed, through a sternotomy, an extra-anatomical by-pass with a Dacron prosthesis soaked in Rifampicin, between the ascending and descending aorta through of diaphragm, with re-implantation of the left common carotid, without the use of cardiopulmonary bypass (CPB), closed the sternotomy, left thoracotomy was performed with removal of the prosthesis and all the infected tissue. Conclusion: Infections in thoracic endoprostheses can be approached safely and with good results in a single procedure, without the need of CBP. 109991 Modality: E-Poster Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Everolimus Reduces Multiple Cardiac Rhabdomyomas in Newborn: Case Report SERGIO ALEXANDRE PEREIRA GONCALVES1, Talita Nolasco Loureiro1, Jessica de Cassia dos Santos Peloso1, Alice Pereira Duque1, Raquel Tavares Boy1 (1) 1Hospital Universitario Pedro Ernesto (HUPE/UERJ), Rio de Janeiro, RJ, Brazil. Introduction: Primary cardiac tumors are rare, with a prevalence range of 0.001%-0.03%. Rhabdomyomas are the most common type of cardiac tumors in children. They are often associated with tuberous sclerosis complex and can cause right or left ventricular outflow tract obstruction, severe heart failure and arrhythmias. Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is suggested to be a promising therapeutic strategy for the involution of rhabdomyomas. Case report: Male newborn (NB), diagnosed with multiple rhabdomyomas by fetal echocardiography, born by cesarean section, gestational age 39 weeks and 3 days, weight 3,405g, head circumference 36 cm, length 50 cm, APGAR 5/9. NB required positive pressure ventilation, orotracheal intubation in the delivery room and received care from neonatal intensive care unit. Thereafter, NB was extubated on the same day and maintained on non-invasive ventilation. On echocardiography: multiple rhabdomyomas, left ventricular (LV) enlargement with severe dysfunction and heart failure. During hospitalization, dobutamine, captopril and digoxin were administered. Everolimus 4.5 mg/m2/day beginning on third day (D3) after birth with clinical, laboratory and echocardiographic tumor involution follow-up and monitoring side effects. Hypochromic macules, presence of astrocytoma in fundoscopic examination and central nervous system tumors in magnetic resonance imaging determined the Tuberous Sclerosis Complex diagnosis. NB presented a 71.2% reduction of cardiac tumor in the LV (7.64 cm2 vs. 2.20 cm2) and a 248% increase in ejection fraction (EF) determined by Simpson's method, from D3 and after 12 weeks of Everolimus use, respectively. After hospital discharge, Everolimus was discontinued due to the restriction of purchasing high-cost drugs. After 13 weeks of Everolimus interruption use, the cardiac tumor showed an increase of 98% (4.37 cm2) but without reduction in EF (53.8%). Currently, the patient remains using captopril (0.08 mg/kg/day) and digoxin (0.01 mg/kg/day) daily and followed-up by pediatric cardiology. Conclusion: Despite being in a phase II clinical trial, Everolimus still improved the involution of cardiac tumors, providing clinical improvement of the heart failure condition and reducing the risks of an extended hospitalization. 110333 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Occlusive Myocardial Infarction (OMI) Without the Classic Electrocardiographic Criteria for ST-Segment Elevation: Importance of Recognizing the Aslanger Pattern in the Emergency Department JEAN MAX FIGUEIREDO1, Tulio Rangel Cardozo2, Caroline Roberta Torquato2, Daniel Xisto Ferreira Lordani2, Otavio Henrique Correa Siqueira Chagas2 (1) Universidade Iguacu; (2) Hospital Municipal de Sao Joao de Meriti; (3) Hospital Geral de Nova Iguacu Male, 72 years old, with oppressive chest pain 2 hours before arrival at the emergency department. History of myocardial infarction 6 years ago, hypertension, smoking, and diabetes. ECG showing ST elevation on D3 without ST elevation on D2 or aVF, ST segment depression with terminal positive T wave in V4 and V5. V1 with ST segment higher than in V2. This electrocardiographic pattern was first described by Aslanger in 2020 and indicates right coronary occlusion in the presence of multivascular atherosclerotic coronary artery disease. The coronary angiography performed after one week showed occlusion of the right coronary artery and severe multivessel lesions including the left main coronary artery. We present here a case report in which the patient presented with occlusive myocardial infarction without the classic electrocardiographic expression of ST-segment elevation in two or more contiguous leads. Two questions need to be answered in the future: the emergency department, should patients with a clinical picture of acute coronary syndrome and electrocardiographic patterns highly suggestive of coronary occlusion, such as Aslanger or De Winter, be promptly thrombolysed when emergency coronary angiography is not available? And it time to change the nomenclature from acute myocardial infarction with ST-segment elevation and acute myocardial infarction without ST-segment elevation to, respectively, occlusive myocardial infarction (OMI) and non-occlusive myocardial infarction (NOMI)? References 1-Aslanger E et al. J Electrocardiol. 2020. 2-Meyers HP et al. Int J Cardiol Heart Vasc. 2021. 110150 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Recurrent Supine Cardioinhibitory Cough Syncope in a Critically Ill COVID-19 Patient NAGELA SIMAO VINHOSA NUNES1, Joelma Dominato1, Paulo Roberto Benchimol Barbosa1, Alfredo de Souza Bomfim1 (1) Complexo Hospitalar de Niteroi; (2) Hospital Universitario Antonio Pedro Background: Reflex syncope is the most common cause of syncope in all age groups and the classic triggers are orthostatic stress, pain, fear and phobia. Cough is an uncommon trigger and when it triggers vagal reflex with syncope it is classified as situational syncope. We report a case in which asystole followed by syncope was always triggered by cough or tracheal aspiration in a patient with critical COVID-19. Case: Female, 40 years old, hospitalized for 40 days with COVID pneumonia, tracheostomized and attached to respirator. She was on daily hemodialysis due to acute renal failure. The cardiology service was contacted to assess recurrent asystole followed by syncope that occurred during airway aspiration or coughing, without concomitant drop in oxygen saturation. Baseline electrocardiogram was normal. 24-hour Holter and continuous telemetry showed numerous sinus pauses of up to 25 seconds . Beta-blocker had recently been introduced and she was on continuous dexmedetomidine infusion. Staff was oriented about the need to avoid hypovolemia, suspend beta-blocker and dexmedetomidine and aspirate the airway with a transcutaneous pacemaker turned on demand, until the events were controlled. In the following days, after these measures, no new episodes of asystole were recorded. Discussion: The causal mechanism of the pauses in this case is compatible with the cardioinhibitory vagal reflex triggered by the Valsalva maneuver due to persistent cough or tracheal aspiration. In the initial phase of the Valsalva maneuver, there is an increase in intrathoracic pressure, that is reflected to vessels in the neck, in addition to a drop in venous return to the heart, which can cause both stimulation of vessel baroreceptors and cardiac mechanoreceptors (Bezold-Jarish reflex). The occurrence of overshoot pressure in the final phase of Valsalva maneuver also can trigger vagal reflex, leading to a reflex cardioinhibitory situational syncope. Recognizing the triggers (hypovolemia and Valsalva maneuver) followed by withdrawal of drugs that can potentiate both triggers and the vagal reflex (dexmedetomidine and beta-blockers) may be essential for the resolution of similar cases in critically ill patients infected with SARS-CoV2, during the COVID-19 pandemic. 110845 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Triple Vessel Spontaneous Coronary Dissection - Not Just Another Heart Attack ASHOK TAHILYANI1, Dr Hannah Gower2, Dr. A. Kotecha2 (1) Royal Devon Universoty healthcare NHS foundation Trust.; (2) Royal Devon and Exeter Hospital Background: Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause of non-atherosclerotic acute coronary syndromes (ACS) and sudden cardiac death . There is very little data that exists in regards to patient clinical characteristics, risk factors, treatment and outcomes. SCAD can be easily missed, as patient characteristics and management differ substantially from typical ACS cases . Results of revascularisation with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are suboptimal1. Conservative management is the preferred option with spontaneous healing of the dissection in the majority of uncomplicated cases . Case Presentations: We present an unusual case of an active 61-year-old male who presented to a local district general hospital with worsening continuous chest pain for 24 hours and arm stiffness, following a week of indigestion-like chest pain. He has noticed increasing fatigue and shortness of breath with exertion in the preceding 7 days. Coronary angiogram revealed triple vessel SCAD of the left anterior descending (LAD), left coronary circumflex (LCX) and right coronary artery (RCA) with long segments of severe, smooth, tubular narrowing, with distal vessels appearing to be normal calibre and disease free. No PCI was attempted. The diagnosis was confirmed with CT coronary angiogram (CTCA). Conclusion: This case highlights an unusual case of triple vessel SCAD, which emphasises the need to recognise SCAD as a cause for ACS presentations as the management differs from classical atherosclerotic ACS cases. It also highlights that whilst management is preferably conservative, revascularisation options may be indicated and PCI is the preferred revascularisation option. However, it is associated with significant challenges and has low reported success rates of <50%. 111456 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Case Report: Multiple Masses in Right Cardiac Chambers Manifesting as Pulmonary Thromboembolism LUIZ MARCELO CRUZ1, Davi Dorval Pereira Cordova1, Mariana Ribeiro dos Reis Arruda1, Marcio Costa Silveira de Avila2, Alexandre David Ribeiro3 (1) Hospital Tereza Ramos; (2) Clinica Pulsar; (3) Clinica Neurocor Cardiac tumors are rare and 80-90% are benign in adults. About half are myxomas, especially in the fourth and sixth decades of life with a slight predominance in women (1.5:1). May be asymptomatic or it can present with respiratory and embolic symptoms such as pulmonary thromboembolism (PTE) if they are in right chambers and also sudden death. Woman, 43 years old, obese, smoker, pulmonary emphysema, deep vein thrombosis in 2016, COVID negative, hospitalized due to pleuritic pain, hemoptysis and hypoxemia one month ago. CT angiography showed involvement of the left pulmonary artery and its branches to the left lower lobe. Echocardiogram showed pulmonary hypertension, enlarged right chambers and supposed thrombi in the right ventricle (RV). Despite anticoagulation, there was no reduction in lesions in RV, neither with fibrinolysis with alteplase. Cardiac resonance showed RV insufficiency and isointense lesions, without enhancement, irregular contour, the largest with 24 x 12 mm in RV output, 28 x 8,5 mm in papilar musculature region of the tricuspid valve and 17 x 4,7 mm in septum, raising hypothesis of myxomas. PET-CT showed no contrast uptake by the lesion. Due to probable benignity of the lesion, the patient opted for conservative treatment and evolutionary control, discharged with home oxigen and warfarin. One year later, exams showed no lesions growth. Although rare and generally benign, cardiac tumors should be part of the differential diagnosis of PTE. 111538 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Transcathehter Valve Implantation in a Patient with Severe Aortic Stenosis Enabling Bone Marrow Transplant for Poems Syndrome Due to Plasmacytoma, a Case Report DIEGO RAUL ROMERO CAWEN1, diego romero cawen1, eduardo schlabendorff1, vanessa santos dos santos1, euler roberto fernandes manenti1 (1) hospital mae de deus; (2) instituto de medicina vascular mae de deus One of the purposes of the cardio oncology team is to provide medical solutions for the oncological patient that enables him to receive the most indicated treatment for his pathology. Patients with heart disease also need optimal cancer treatment and cancer diagnoses. When cardiac surgery is indicated, hard decisions must be made and a multidisciplinary point of view promotes a qualified opinion. We present a case of a 50 year old male with a history of pain and paresthesia of upper and lower limb extremities, defined as sensory-motor non demyelinating polyneuropathy. He had a medical history of type 2 diabetes mellitus and hypertension. In April of 2018 he was hospitalized due to a severe aortic stenosis with surgical indication. Cardiac catheterization showed normal coronary arteries. In the preoperative evaluation a serum monoclonal peak was seen in proteinogram. Medullogram revealed 1.5% of non-clonal plasma cells. His whole body MRI showed an expansive lesion located in the proximal diaphysis of the right tibia, measuring 7.0 x 2.0 cm. Biopsy findings indicated a plasmacytoma. VEGF levels were 1294 ng/l indicating POEMS. He underwent radiotherapy and received dexamethasone, with a non satisfactory response. Sternum and fifth dorsal vertebra infiltration were detected in PET-SCAN. Systemic treatment was indicated and at this time patient was symptomatic from his AS. He suffered an acute pulmonary edema during mediastinal biopsy. His echocardiogram revealed a bicuspid aortic valve with severe aortic stenosis. After consultation with the heart team, the patient was judged to be an EuroScore II intermediate. We therefore decided to perform TAVI to reduce the interval between AS treatment and cancer treatment, preventing malignant tumor progression. In addition, benefits of TAVI have been reported in cancer patients because it does not require cardiopulmonary bypass. These include reducing the risk associated with tumor bleeding secondary to anticoagulant disorders and administration of anticoagulants, and reducing tumor dissemination with immunosuppressive and inflammatory effects of the cardiopulmonary bypass. After the procedure, the patient had a favorable evolution and a marrow transplant was performed. This point-of-care treatment was conducted due to the expertise of the multidisciplinary heart team. 111005 Modality: E-Poster Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Danon Disease: A Case Report PAULO LEAO ANDRADE1, Larissa Neto Espindola2, Maria Cristina Costa de Almeida3, Maria Gabriela Costa de Almeida3, Fernando Carvalho Neuenschwander4 (1) Hospital Sao Vicente de Paulo, Itabirito-MG; (2) Hospital Santa Izabel, Salvador-BA; (3) Centro Universitario de Belo Horizonte; (4) Instituto Orizonti, Belo Horizonte - MG Case Presentation: A 17-year-old male, asymptomatic, amateur soccer player, sought a cardiologist after the sudden death of his maternal uncle at age 43 due to acute myocardial infarction, confirmed at necropsy. Apparently, he did not show any muscular, cognitive, cardiological or other system involvement. The electrocardiogram performed in the office met criteria for left ventricular (LV) hypertrophy and suggested the presence of ventricular preexcitation, such as the presence of delta wave and a short PR interval. Holter monitor showed preserved sinus automatism, ventricular preexcitation, infrequent ventricular extrasystole. Transthoracic echocardiogram showed hypertrophy of the middle and apical segments, suggesting the possibility of apical hypertrophic cardiomyopathy (HCM). He had normal LV ejection f n but incipient signs of systolic dysfunction (reduced longitudinal global strain(-13%). He underwent cardiac magnetic resonance which showed asymmetric HCM with areas of late enhancement in approximately 25% of the myocardial mass, in addition to increased thickness of the right ventricular free wall with small areas of late enhancement in its apical portion and signs of increased trabeculation. In view of the findings of HCM + ventricular preexcitation, we chose to perform a genetic test, which confirmed a mutation in the LAMP2 gene. Opted to implant an implantable cardioverter defibrillator for primary prophylaxis of sudden cardiac death. The patient is doing well, with no signs or symptoms of heart failure and no shock therapies to date. Discussion: Mutations in X-linked lysosome-associated membrane protein gene (LAMP2; Danon disease) produce a cardiomyopathy in young patients that clinically mimics severe HCM due to sarcomere protein mutations. However, the natural history and phenotypic expression of this rare disease is incompletely resolved and its identification may have important clinical implications. Early identification of Danon disease in male is extremely important for patient care because rapid clinical deterioration leading to cardiac death occurs in young men before 25 years of age, in general. Heart transplantation is the reliable treatment once the occurrence of heart failure and should be considered as early as possible due to its rapid progression. New hope is emerging with the possibility that gene therapy could change the course of this dreaded disease. 111024 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Treatment of Pulmonary Vein Stenosis After Atrial Fibrillation Catheter Ablation: The Key to Succeed! FABIO RODRIGO FURINI1, Carlos Antonio Abunader Kalil1, Anibal Pires Borges1, Oscar Ivan Lopez Leon1, Valter Correia de Lima1 (1) Santa Casa de Misericordia de Porto Alegre Introduction: Pulmonary vein (PV) severe stenosis post atrial fibrillation (AF) catheter ablation is a rare event (<0.5% of treated veins) that can cause dyspnea, pneumonia, pleural effusion, hemoptysis, pulmonary hypertension and even death. Percutaneous stenting PV, instead of balloon angioplasty alone, is effective in order to reduce the chances of restenosis. Stents implanted with 8 mm or larger are related to better outcomes. Case Description: 60 y/o patient with AF since 2019 and two ablations of the arrhythmia. Three months after the ablation he presented with tiredness and CT scan which showed a pulmonary infiltration into the bronchus from the basilar left pulmonary trunk. The investigation ruled out neoplasia. A 3D reconstruction of the image showed the complete occlusion LIPV and a critical stenosis of the LSPV, with reference diameters of 15 mm on the last one. Therefore, we only address the LSPV. The procedure was performed in the cath lab by the interventional cardiology and electrophysiology teams. Invasive measurements of pulmonary pressures showed postcapillary pulmonary hypertension (mean arterial pulmonary pressure of 38 mm Hg and wedge pressure of 37 mm Hg) and the translesional pressure gradient measured by TTE Doppler US was 27 mm Hg on LSPV. Sequential dilatations were performed, and finally a 12 mm diameter balloon with a Palmaz Genesis XD 1019 was fully expanded at the lesion. Angiography showed an excellent angiographic result and the translesional pressure gradient by Doppler fell from 27 mm Hg to 5 mm Hg . The patient was discharged from the hospital on the second day after the procedure. Conclusion: PV stenosis after AF catheter ablation is a rare and insidious event. Treatment can be challenging and require multidisciplinary expertise. 111030 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM St-Segment Elevation Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease (Minoca) in a Patient with SARS-COV2 Infections: A Case Report INGRID LOUREIRO DE QUEIROZ LIMA1, RODRIGO FERNANDES CASTRO2, TALITA CARVALHO2, ANGELO BRUNO PAGOTO2, CARLOS ROBERTO ROHENKOHL EVANGELISTA SANTOS2 (1) UNIVERSIDADE FEDERAL DO AMAZONAS; (2) HOSPITAL DO CORACAO FRANCISCA MENDES Background: Since the pneumonia outbreak in December 2019 in the province of Wuhan, China, the SARS-COV-2 infection has spread to hundreds of countries and emerged as a pandemic crisis. In addition to the fact that underlying cardiovascular conditions have a negative impact on the prognosis of these patients, the virus can also affect directly the cardiovascular system through myocardial injury, cardiac failure, arrythmia, myocarditis and shock. Hypercoagulability state is also described due to the SARS-COV2 infection. Series of patients with myocardial infarction without coronary artery disease were described and intracoronary thrombus was described as a possible cause. Case Report: A 58 y-o male was admitted in a public hospital in Amazonas/Brazil due to acute respiratory syndrome on May 11th, with low oximetry. He received oxygen support with nasal catheter O2 and remained stable for 8 days. On May 18th he presented a syncope without prodrome at the clinical ward. EKG showed a ventricular tachycardia, promptly reverted by electric cardioversion. The new EKG showed sinus rhythm and ST-elevation in inferior and lateral leads, immediately treated with thrombolytics. The coronary angiogram performed three days after the event showed coronary arteries without obstruction. Cardiac MRI evidenced transmural infarction in inferior and lateral walls. Discution: Myocardial injury is observed in some patients due to SARS-COV-2 infections and it can be caused not only by plaque rupture but also by inflammatory storm and massive citokyne release, coronary spasm, microthrombus or vascular an and endothelial direct lesion. The absence of coronary artery disease in the angiogram and the previous history of thrombolytic treatment of this patient points toward a possible intracoronary thrombus causing the myocardium infarction. The evidence of a transmural contrast enhancement in the cardiac MRI reinforces the diagnostic of myocardial infarction and helps differentiating it from a myocarditis. 112421 Modality: E-Poster Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Pinch Off Syndrome: A Rare Case Reported GISELLE LAURITZEN DUARTE1, Andre Sansonio de Morais1, Sergio Medeiros da Silva Junior2, Daniel Cavalcanti de Carvalho3, Flavio Roberto Azevedo de Oliveira4 (1) Hospital Dom Helder Camara (HDH); (2) Hospital Dom Helder Camara (HDH); (3) Hospital Dom Helder Camara (HDH); (4) Hospital Dom Helder Camara (HDH) Introduction: The central venous catheter is a device used in critically ill patients in emergencies and ICUs. Among the vascular complications, Pinch-off syndrome is related to puncture of the subclavian vein and occurs when the catheter is compressed between the clavicle and the first rib, causing laceration, fracture and embolization to the right chambers or pulmonary circulation, with high rates of serious complications, including death. We report the case of a patient with a finding of a foreign body in the coronary sinus during an echocardiogram performed in the context of heart failure decompensation. Case Description: SJF, male, 62 years old, with heart failure (HF) with reduced ejection fraction (EF = 29%), admitted to the hospital with decompensated HF profile B, underwent transthoracic echocardiography (TTE) with image being visualized irregular, mobile, hyperechoic in the right atrial cavity, measuring about 5 cm, which seemed to be attached to the interatrial septum, or coming from the coronary sinus, with mobile elements attached to the extremity - neoplastic mass? thrombus? catheter tip covered by thrombus? A chest tomography was performed and a linear image with high density located in the topography of the coronary sinus and right atrium was visualized, a nonspecific finding, which may be related to a foreign body (catheter fracture?). The case was discussed at a clinical meeting, and the diagnostic hypothesis of Pinch-off Syndrome was raised, with a probable etiology due to a fractured catheter in an internment performed 2 years ago in another Service. Anticoagulation was started and a hemodynamic approach was chosen. Before the procedure, a new TTE did not identify images suggestive of thrombi adhered to the catheter. The interventional procedure was uneventful, with rapid removal of the foreign body and confirmed to be a catheter tip. The patient evolved hemodynamically stable and was discharged asymptomatic with optimized treatment for HF. Conclusion: Pinch-off syndrome is associated with high rates of serious complications. The finding of an embolized catheter fragment on imaging is typical. The removal of the fragment is mandatory and the hemodynamic procedure is the first option. The thrombotic burden associated with the catheter initially made it difficult to define the nature of the fragment and data from the retrospective anamnesis were essential for the conclusion of the diagnosis. 111143 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Post-Covid Syndrome and Systemic Arterial Hypertension (SAH) in a Young Adult: A Case Report of the Functional Status After a Cardiopulmonary Rehabilitation Program ANA INES GONZALES1, Ana Ines Gonzales1, Lucas Lemonie Zunino1, Josie Budag Matsuda1, Luis Otavio Matsuda1 (1) Centro Universitario para o Desenvolvimento do Alto Vale do Itajai (UNIDAVI) Introduction: Previous Systemic Arterial Hypertension in individuals affected by COVID-19 can lead to a worse prognosis, increase complication rates and reduce functional capacity. In view of this, exercise-based cardiopulmonary rehabilitation may be able to promote functional improvement. This study reports the case of a male patient, post infection by COVID-19, with a previous diagnosis of Systemic Arterial Hypertension, submitted to a cardiopulmonary rehabilitation program. Case Description: V.N.F, 24 years old, male, diagnosed with Systemic Arterial Hypertension prior to SARS-Cov-2 infection, referred to a cardiopulmonary rehabilitation program, due to fatigue and lack of physical conditioning in usual life activities 4 months post infection. post-intervention assessment: Post-COVID-19 Functional Status Scale (PCFS), 1-minute Sit and Stand Test (SST1), 2-minute Stationary Gait Test (2MWT) and 6-minute walk test (6MWT). The rehabilitation program was carried out for 8 weeks, twice a week, based on: 1) aerobic exercises on a treadmill, 2) strength and muscular endurance exercises, developeded in a progressive and individualized way. Patient started the first session with continuous aerobic exercise for 10 minutes, at 3.5 km/h, without incline, reaching Borg 4, heart rate of 119 bpm (61%) and muscle strengthening exercise in upper limbs with an elastic band, reached Borg 3 for dyspnea. Patient completed 100% of the sessions performing, in the last session, aerobic exercise in running for 20 minutes, at 6.5 km/h, without incline, final Borg of 0.5 with heart rate of 148 bpm (75%) and 8 minutes in circuit associating exercise bike (load 4) interspersed with squat on a trampoline, with final Borg of 0. After 8 weeks, the following data were evidenced: PCFS (Grade 1 vs Grade 0), SST1 (18 repetitions/final Borg 5 vs 23 repetitions/Borg end 0), 2MWT (66 elevations/Borg end 5 vs 94 elevations/Borg end 0), 6MWT (510 m vs 552 m), respectively. The patient completed 100% of the intervention sessions. Conclusions: The results show that performing cardiopulmonary rehabilitation for 8 weeks was able to improve the functional status of a young adult individual with arterial hypertension and symptoms of post-covid syndrome. 111266 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR IMAGING Positioning of the Left Ventricular Lead Target by Gated Spect Determining Reverse Ventricular Remodeling ERIVELTON ALESSANDRO DO NASCIMENTO1, Fernando de Amorim Fernandes1, Zhuo He3, Weihua Zhou3, Claudio Tinoco Mesquita1 (1) Universidade Federal Fluminense - UFF; (2) Instituto Estadual de Cardiologia Aloysio de Castro - IECAC; (3) Michigan Technological University - MTU A 66-year-old female with ischemic heart failure had an ejection fraction (EF) value of 14%, with left bundle branch block, and was considered functional class IV despite optimized therapy. Subjected cardiac resynchronization therapy (CRT) with left ventricular (LV) lead positioning targeted by the last viable segment was determined by GATED SPECT. After CRT, the EF value was 57%. LV contraction was successfully analysed by radionuclide ventriculography at first, however, the addition of GATED SPECT phase analysis and its subsequent validation, has shown excellent potential in determining left ventricular mechanical dyssynchrony. Studies that report on the placement of the LV lead are consistent with the findings of the last contracting segment identified by GATED SPECT phase analysis and show significant clinical improvement. Recent VISION CRT data demonstrated that dyssynchrony improvement, but not target lead placement, predicts clinical outcomes in CRT. Parameters of the LV geometry obtained by GATED SPECT phase analysis were able to predict a super-response to CRT. This report demonstrates a super-response with a significant change in the LV eccentricity index and LV shape in both LV end-systole and end-diastole, denoting reverse remodelling after CRT target by GATED SPECT. 111276 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Cardiac Amyloidosis and Multiple Possible Cardiotoxicities in the Same Patient Making it a Complex Diagnosis VANESSA SANTOS DOS SANTOS1, Eduardo Schlabendorff1, Diego Romero Cawen1, Euler Fernandes Manenti1 (1) Hospital Mae de Deus (HMD) Cardiac amyloidosis has been historically difficult to diagnose due to lack of specific symptoms and necessity of biopsy. In the oncologic population this becomes even harder, since there may be multiple confounding factors related to the essential neoplasm and its treatment cardiotoxicities. We present a case of a 72 year old male that developed symptomatic supraventricular arrythmias and congestive heart failure (CHF). He followed with repeated episodes with hemodynamic instability. Attempts to ablate the arrhythmia were unsuccessful and because he had a left atrial tachycardia, we chose to ablate the atrioventricular node and implant a dual chamber pacemaker in the deep interventricular septum. To rule out ischemic heart disease, he underwent a cardiac resonance which showed signs of global left ventricular systolic dysfunction due to diffuse hypokinesia with an ejection fraction of 35% and extensive areas of discontinuous delayed enhancement, predominantly mesocardial and subepicardial (non-ischemic pattern), diffusely compromising the left ventricle. These findings suggested an inflammatory process of the myocardium (post-infectious or drug related) or an infiltrative cardiomyopathy - presumably amyloidosis, although not a typical imaging presentation which usually appears with predominance in the subendocardial areas. Amyloidosis was pursued and after ruling out light chain amyloidosis by laboratory tests, he performed a pyrophosphate scintigraphy. The result was a heart to contralateral (H/CL) ratio of 1,7 (a ratio of >1,5 is considered to strongly suggest transthyretin amyloid deposition). He also performed genetic testing and we are waiting the identification of the mutation. His treatment for CHF was optimized and he was discharged with improved symptoms. His past medical history was notable for a non-Hodgkin's lymphoma diagnosed in 1983 and treated with chemotherapy, which included an anthracyclic, and radiation therapy of the mediastinum. In 2013 he was diagnosed with a prostate cancer and underwent prostatectomy, followed by androgen deprivation therapy (ADT) with an GNrH antagonist, also with known cardiotoxicity. All of these aggressors may have contributed to the ventricular dysfunction and appearance of arrythmia, presumably being of multifactorial etiology. But we highlight the need to pursue the diagnosis of amyloidosis as the correct identification of this disease is crucial for the initiation of potentially life-saving treatments. 111305 Modality: E-Poster Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Restrictive Desmin Deposition Cardiomyopathy CARLOS MANOEL DE CASTRO MONTEIRO1, Lais Olivo Rossi1, Luisa Carvalho Benedito1, Raul Cordeiro Pessanha1, Mireya Mendonza Rodrigues1 (1) Hospital Samaritano Paulista Introduction: Heart failure (HF) is the end of many diseases that affect the heart, which explains its increasing prevalence. Restrictive cardiomyopathy is the least prevalent form of cardiomyopathies. This case report aims to discuss restrictive cardiomyopathy, addressing a rare etiology that is desmin deposit. Case description: Male patient, 26 years old, with cardiomyopathy diagnosed 3 years ago, evolving for 2 months, with swelling in the lower limbs and progressive dyspnea. He was admitted to our institution with dyspnea on minimal exertion and signs of low cardiac output, being diagnosed with HF profile C. Family history: father, aunt and paternal cousin have cardiomyopathy. The ECG showed atrial tachycardia with RBBB and the echo showed significant increase in both atria, slight increase in both ventricles and significant diffuse involvement of the RV and LV with EF = 45%. Magnetic resonance imaging (MRI) of the heart showed late non-ischemic enhancement. Given the clinical picture, family history, echocardiogram and "MRI", genetic testing was indicated. The complete exome sequencing identified a heterozygous pathogenic variant in the "DES" gene related to a restrictive cardiomyopathy secondary to the accumulation of desmin, which is the most important intermediate filament of skeletal and cardiac musculature, functioning as a protein cytoskeleton. Cardiac manifestations can occur in the form of restrictive cardiomyopathy, conduction system disease, arrhythmias, and sudden death. The patient presented worsening heart failure, requiring vasoactive amines, "IAB" and "ECMO", being listed on the heart transplant waiting list. Transferred to a transplant center, undergoing heart transplantation, however, in the postoperative period, he presented sepsis, progressing to death. In this clinical case, a pathogenic variant associated with autosomal dominant/recessive cardiomyopathy was identified. The genetic test elucidated the etiology of cardiomyopathy, the refractoriness of heart failure to clinical treatment and optimized hemodynamic support, included the indication for heart transplantation (HT). Conclusion: This clinical case reports the importance of genetic tests in the etiological diagnosis of cardiomyopathies and "HT" is considered a therapeutic option in patients with advanced and refractory HF. 111327 Modality: E-Poster Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Impact of Daylight Saving Time Transitions in Cardiovascular and Metabolic Acute Events: A Preliminary Exploratory Study MIGUEL MEIRA E CRUZ1, Mauricio Machado da Rosa1, Michele Gomes da Rosa1, Dario Acuna Castroviejo2, Amelia Feliciano3 (1) Centro Cardiovascular da Universidade de Lisboa, Lisbon School of Medicine, Lisbon, Portugal; (2) Centro de Investigacion Biomedica, Universidad de Granada, Granada, Spain; (3) Faculdade de Medicina, Universidade Catolica, Lisbon, Portugal Introduction: Daylight saving time (DST) imposes a twice-yearly hour shift. This circadian challenge has been associated to detrimental health effects including an increased incidence of acute myocardial infarction following the springtime transition and increased ischemic stroke following both DST transitions. While cardiovascular consequences of DST are still controversial, the possibility that DST may impact metabolic disorders was never discussed before. We aimed to investigate a possible relationship between cardiovascular and metabolic acute events and DST transitions. Sample and Methods: All acute cardiovascular and metabolic events occurring during the 3 days before (pre transitional period) and after (post transitional period) the spring and the autumn shift were extracted from the records of two main hospitals in Lisbon, Portugal. The variation between the number of cardiovascular and metabolic events observed in the post transitional and pre transitional periods from both ocasions were statistically compared. Results: From the total of 492 patients (47.2% males) recurring to the hospital either during 2018 spring time transition or same year autumn time transition, with a mean age of 70.36 +- 16.1 years old, 89% presented with cardiovascular events whereas 11% presented with metabolic events. The variation amplitude from the 3 preceding days to the 3 subsequent days was +8.33% for cardiovascular and +50% for metabolic events in the spring transitional period. The same variation in the autumn transitional period was +16.13% and -65%, respectively. Conclusion: Results from this preliminary study corroborate the belief that a conflict between DST and cardiovascular health could be expected in both DST transitional periods although with important seasonal differences. Further, a relevant impact on metabolic status was also showed for the first time. While these results may reflect an impact of the circadian misalignment on cardiometabolic functions, the clinical meaning of such interaction may rely on further complex interaction with circannual oscillations from seasonal timing systems for which future exploration is warranted. 111419 Modality: E-Poster Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Acute Myocardial Infarction by Spontaneous Coronary Dissection ANA AMARAL FERREIRA DUTRA1, Isabelle Mendes Rodrigues Salomao1, Luanna Damasceno Amaral de Sousa1, Louise Freire Luiz1, Bruna Pereira de Mendonca1 (1) Hospital Pro Cardiaco Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), which can lead to sudden death. SCAD is an important differential diagnosis of chest pain and should be considered especially in young women with few risk factors for coronary artery disease (CAD). Case report: Patient, 63 years old, female, grade IV obesity and arterial hypertension, and positive family history of CAD. Admitted to the emergency department of a quaternary hospital with hypertensive emergency (BP 230 x 92 mmHg) associated with typical chest pain, at rest, radiating to the back and upper limbs, with no improvement and/or worsening factor. She reported an intense episode of anxiety the night before the pain. Physical examination showed no changes in cardiopulmonary auscultation, blood pressure was similar in the upper limbs and no lower limb edema. A loading dose of acetyl salicylic acid (ASA) was performed and nitroglycerin infusion was started. The admission electrocardiogram showed: sinus rhythm, ST infra of DIII and aVF. First troponin of 312 ng/mL (ultrasensitive) and other tests without changes. Bedside echocardiogram with preserved biventricular systolic function, with no change seen in the ascending aorta. The patient evolved with chest pain, refractory to clinical treatment, and therefore, an emergency hemodynamic study was chosen. Coronary angiography (CAT) showed spontaneous coronary dissection (diagonal artery). We opted for conservative treatment with dual antiplatelet therapy (ASA and Clopidogrel), high-potency statin and strict control of the dual product (heart rate and systemic blood pressure). Discussion/Conclusion: The incidence of SCAD is higher in young women and presents as ACS, it is extremely important to make the differential diagnosis of chest pain. It may be related to fibromuscular dysplasia, pregnancy, puerperium and hormone replacement. The approach to patients should follow the normal ACS protocol, but it should be taken into account that CAT can aggravate the dissection. Recent studies have shown benefits with conservative treatment in low-risk DEAC, as most cases evolved with spontaneous healing of the intramural hematoma after 30 days. 111501 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Tumor Thrombus Ascending Through the Inferior Vena Cava and Extending Into the Right Atrium Successfully Removed by a Multidisciplinary Surgical Team in a Young Patient with Advanced Testicular Cancer EDUARDO SCHLABENDORFF1, Vanessa Santos dos Santos1, Diego Raul Romero Cawen1, Marcelo Haertel Miglioranza1, Euler Roberto Fernandes Manenti1 (1) Hospital Mae de Deus de Porto Alegre Introduction: Tumor thrombus is a rare complication of testis cancer and needs appropriate treatment including chemotherapy and surgery. Case report: A 23-year-old man was hospitalized in October 2019 with epigastric pain, dyspnea, tachycardia and tachypnea without hypoxemia. The EKG showed a S1Q3T3 pattern. Laboratory revealed mild anemia, leukocytosis, normal troponin and BNP levels. D-dimer levels were extremely high. Point-of-care echocardiogram followed by a 3d echocardiogram showed a large mobile mass compatible with a thrombus inside the right atrium that incursed towards the right ventricle in diastole. CT angiography revealed a probable tumor thrombus originated in the left renal vein, entering the inferior vena cava and ascending into the right atrium. There is also an increase in volume of the left testis and a voluminous expansive mass next to the left renal hilum most likely associated with lymph node conglomerate. Anticoagulation was started even though CT scan was inconclusive for pulmonary embolism. The next day, the patient presented clinical worsening with signs of low output. Due to the high chance of response with cytotoxic chemotherapy in testicular tumors, chemotherapy with Bleomycin, Etoposide and Cisplatin (BEP) was guided by the oncologist. The patient underwent a left radical orchiectomy. After 4 courses of BEP chemotherapy the tumor markers normalized. A surgical team composed of cardiovascular, urological and oncological surgeons performed a triple surgery at the same surgical moment to remove the tumor thrombus using extracorporeal circulation (figure above). It was also performed left nephrectomy and retroperitoneal and pelvic lymphadenectomy. Advanced testicular cancer was diagnosed with a clinical stage of pT2-Nx-MO-S3, which has a poor prognosis. The pathological examination revealed a mature teratoma. The patient has been disease-free since surgery. Conclusion: A multidisciplinary approach is necessary to treat patients with tumor thrombus secondary to advanced testicular cancer. 111659 Modality: E-Poster Researcher - Case Report Category: NURSING Nurse's Role as a Scientific Educator in a Project to Care for AMI with ST Elevation in the Public Health Network JOSELITO ADRIANO DA SILVA1, Nathalia Pereira1, Paola Begliomini2 (1) Allm Inc; (2) Boehringer Ingelheim Introduction: Acute Myocardial Infarction (AMI) has a high rate of morbidity and mortality in Brazil and worldwide. In 2017, DATASUS recorded that AMI was responsible for 10% of hospitalizations in the Unified Health System (SUS) and 7% of all deaths in the country. In view of the magnitude of the disease and the benefit of the treatment being time-dependent, in 2019 the Sprint Project was started: a public-private collaboration initiative aimed at optimizing care for patients who enter the service with AMI with supra of ST through the development of care networks in SUS units, promoting rapid diagnosis and the appropriate choice of therapeutic strategy in a timely manner. Methods: This is an experience report on the role of the nurse as a Scientific Educator in the Sprint Project, which acts as an interlocutor and facilitator of information within the public service of care and manager of the results that are obtained through the use of a mobile application. that allows communication between the services involved, for example UPA and hemodynamics. Results: Currently the project is in 4 states and 06 cities promoting the integration between emergency services and the reference hemodynamics center, as agreed with the municipal/state health departments. With a strategic role, the nurse who works as a Scientific Educator must have experience in the care of patients with AMI and will actively work with the leader ("Champion)" of the network and the services involved, supporting the structuring of the care network in all areas. the phases. Project actions include: project presentation, diagnostic evaluation of the service from the physical structure to the service flow, analysis of improvement opportunities, construction of a multidisciplinary plan, training and supply of tools according to needs, periodic monitoring of networks and management of quality of care indicators based on the European ST-supra AMI Guideline. Conclusions: It is concluded that the role of the Scientific Educator nurse is strategic and visionary, being considered by the care network as a partner to assist in the organization of the AMI care flow, strengthening the bond with the services involved, thus minimizing delays in treatment. and reducing mortality from AMI with ST elevation. The nurse's role is, therefore, fundamental in the periodic maintenance of the project, reducing errors, engaging the professionals at the end and contributing to improve the journey of the patient with AMI. 111696 Modality: E-Poster Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Mitral Valve Infective Endocarditis with Septic Embolization in a Young Patient: A Case Report and Review of Literature CAMILA RICHTER1, Priscilla Vicente Lista1, Carlos Alberto Kenji Naashima1, Jessica Woehl1, Thammy Lethicia de Sousa Silveira1 (1) Hospital Angelina Caron Introdution: Infective endocarditis (IE) is a serious disease that requires treatment by a multidisciplinary team, involving cardiologist, infectious disease specialist and cardiovascular surgeon, as well as neurologists in cases of involvement of neurological events. Case Report: DB, 39 years old, male, no previous diseases. No vices. The patient was admitted in-hospital with fever, headache, evolving into mental confusion and decreased level of consciousness and strength in legs. Moreover, the cardiac auscultation presented a more audible systolic murmur in the mitral focus. The cranial tomography revealed right frontal and left temporal ischemia (figure 3). The sorologies were required and were negative for the hepatitis B, C, Human Immunodeficiency virus (HIV) e syphilis. Meningitis was ruled out after liquor evaluation. Janeway lesions were observed in the toes (figure 4). A bedside investigation was performed with Phelcoma portable retinograh and Roth spots were identified (figure 1). Blood culture was positive in less than 24 hours for Staphylococcus aureus. Transesophageal echocardiogram confirmed suggestive image of mitral vegetation on the atrial face (figure 2). The mitral valve was replaced by a biological prosthesis. Conclusion: This case report showed the critical course of the IE, presenting with the worst possible manifestations for the disease. The surgical treatment is the principal recommendation for this case. 111728 Modality: E-Poster Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Pseudoaneurysm Due to Coxiella Burnetti Endocarditis Successful Treated with a Vascular Plug CLAUDIO QUERIDO FORTES2, Paula de Medeiros Pache de Faria1, Ilan Gottlieb1, Luiz Antonio Carvalho1, Valdo Jose Carrera1 (1) Casa de Saude Sao Jose; (2) Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro Introduction: Infective endocarditis (1E) with negative blood cultures represents a small percentage of the cases, however, in many of these episodes it is possible to identify the microorganism causative through serological and/or molecular methods. Case Report: A 65-year-old male with a bicuspid aortic valve, diagnosed with 1E with persistently negative hemocultures, complicated by aortic paravalvular abscess evidenced by transesophageal echocardiography (TEE) and by aortic angiotomography. Empiric treatment with ampicillin plus sulbactam associated with ceftriaxone was started and valve replacement by biological prosthesis was performed. After 6 weeks on antibiotics therapy, he was discharged. Three months later fever returns and after an extensive investigation PCR for Coxiella burnetii was positive in blood and in the specimen from hepatic biopsy and IgG phase I, II and IgM phase I was higher than 1;1024. Treatment with doxycycline and hydroxychloroquine was started. At that time TEE and angiotomography evidence an abscess which, in few days, resulted in pseudoaneurysm. As Eurocore was too high and there were technical difficulties for a reoperation it was chosen to use a vascular plug with which a successful closure of the communicating orifice was achieved. Patient was discharged with oral treatment and after 4 months of clinical and echocardiographic follow up he is still doing well without any sigh of recurrence. Conclusion: When the Euroscore is too high and the surgical procedure almost impossible to be performed, the use of devices such as the vascular plug might be a plausible alternative, as it was for the patient here reported. 111773 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Analysis of Intracranial Compliance During Transcatheter Aortic Valve Implantation: Case Report and New Perspectives ROBERTO ABDALLA FILHO1, Hugo Bertipaglia1, Cledicyon Eloy da Costa1, Mauricio Marson Lopes1, Gustavo Frigieri2 (1) Hospital Samaritano de Campinas, Campinas, SP, Brasil; (2) Brain4care, Brasil The connection between cardiac alterations and brain function is an area still under inquiry. The use of tools for neurological monitoring of patients with heart dysfunction may represent a possibility to achieve better outcomes. This report will discuss the use of a new non-invasive intracranial compliance monitoring tool for patients with heart dysfunction prior to and following transcatheter aortic valve implantation (TAVI). Case description: A 80-year-old patient with progressive fatigue with marked aggravation during the past year. The image tests showed aortic valve fibrocalcification with severe stenosis and severe atheromatosis in the aorta, that contraindicated de transfemoral access for TAVI and made the transapical access the eligible option. Intracranial compliance (ICC) monitoring was done prior to TAVI and post-procedure. Results: The patient showed improvement in the peak gradient, which went from 125 mmHg before the procedure to 14 mmHg after, and at the peak speed initially of 5.58 m/s and 1.88 m/s after TAVI. The ICC of the patient presented values altered before TAVI, with a Ratio of P2/P1 of 1.38 and time to peak of 0.27, values suggestive of intracranial hypertension. After the procedure, ICC was normalized, with a P2/P1 ratio of 0.71 and a time to peak of 0.14 (p < 0,001). Conclusion: The noninvasive system was able to show alterations in intracranial compliance with cardiac alterations, as well as improvement after TAVI. 111787 Modality: E-Poster Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Aortoesophageal Fistula Caused by Thoracoabdominal Aortic Aneurysm Rupture: A Case Report NINA NOVAES AZEVEDO1, Bruno Daniel Ferrari1, Fernanda Correa de Oliveira Lima2, Flavia Correa de Oliveira Lima2, Victor Sandi Mori Salvador2 (1) Curso Intensivo de Revisao em Cardiologia Clinica - Rio de Janeiro; (2) Hospital Regional de Presidente Prudente - HRPP Introduction: Aortoesophageal fistulas (AEF) are rare and require rapid diagnosis. They represent a major therapeutic challenge because of their high morbimortality; 2/3 of these are a consequence of thoracic aortic rupture, resulting from aneurysms or traumas. Case description: M.E.M.R., 87 years old, female, from Sao Paulo countryside, was admitted with hematemesis to the Emergency Room in a private hospital in the area. Personal history included arterial hypertension and diabetes mellitus. On physical examination, cardiac and pulmonary auscultation showed no findings, no carotid bruits, Glasgow 15, no focal neurological deficit. After clinical stabilization, the conduction of Upper Digestive Endoscopy showed esophageal aortic fistula, which was non-communicating, thrombosed and without active bleeding. The computed tomography of the chest showed a thoracoabdominal aortic aneurysm of approximately 70 mm in diameter, with the presence of extensive intramural thrombus from the abdominal aorta to the ascending aorta trunk, without signs of acute dissection, with esophageal compression. Assessment through vascular surgery indicated no intervention with endoprosthesis, due to her advanced age. Because of her hemodynamic stability, a second analysis showed that intervention was recommended, and she was inserted in the Vacancy Regulation Center (CROSS). The day before the procedure, a new bleeding led to her death. Conclusion: AEFs are rare and fatal presentations of thoracoabdominal aortic ruptures. The patient's advanced age was a decisive factor in indicating the intervention, together with her hemodynamic stability. Despite the high morbimortality of AEFs, the effectiveness of the entire system of early diagnosis, stabilization, and treatment is essential for a complete patient care, often being successful, and sometimes unsuccessful. 111820 Modality: E-Poster Researcher - Case Report Category: CARDIO-ONCOLOGY Pericardial Effusion and Mediastinal Mass FLAVIA CRISTINA CARVALHO DE DEUS 1, Aurora Felice Castro Issa1, Claudio Domenico Sahione Schettino2, Carlos Jose Coelho de Andrade3 (1) "Curso de Pos-Graduacao em Cardiologia da SBC/INC/INCA, Rio de Janeiro, RJ, Brasil"; (2) Hospital Pro Cardiaco; (3) Instituto Nacional do Cancer - INCA Introduction: Mediastinal masses with pericardial effusions constitute a great challenge that shows the importance of the Cardio Oncology specialty. Case Description: S.R.P., 73 years old, female. Admitted to the emergency room with progressive dyspnea. Stable vital signs, but dyspnea with saturation 88%. Performance Status of 2. Laboratory with anemia, hypoalbuminemia and elevated C-reactive protein. Echocardiogram showed preserved biventricular function, strain - 16, presence of a mass anterior to the mediastinum (15 x 13 cm), pericardial effusion without restriction and bilateral pleural effusion. Angioresonance showed right paracardiac mass that insinuates into the right atrium and extends to the aorta. It was requested an Oncologist Opinion. FDG PET scan showed hyper uptake in the right mediastinal mass with SUV 24 (Standardized Uptake Value). Values greater than 2 are suggestive of malignancy. CT-guided liver biopsy was suggestive of Sarcoma. Doxorubicin 75 mg/m2 was started. The electrocardiogram was monitored for the risk of QT interval prolongation and serial measurements of troponin and BNP were performed. Immunohistochemical panel result changed the diagnosis to GIST (Gastrointestinal stromal tumors) and Imatinib 400 mg orally once a day was started. Genetic biopsy test did not show mutations. Follow-up CT scans and echocardiogram showed no response to Imatinib. She presented with severe headache after the tomography and sudden coma with ventricular bleeding and unfortunately evolved to death. GISTs are sarcomas of cells of the gastrointestinal tract (cells of Cajal). They have CD 117 surface markers (C-kit) involved in tumor growth. They are rare tumors, diagnosed incidentally, occur between 50 years old and are most frequent in the stomach and small intestine. Only 5% in other locations. About 30% progress to malignancy. The final diagnosis is based on immunohistochemistry and genetic tests. The treatment is surgical resection and therapy with tyrosine kinase receptor inhibitors. The first choice is Imatinib at a dose of 400 mg per day. Early tumors have a 90% survival at 5 years, but tumors larger than 11 cm and metastatic have a worse prognosis. Conclusion: Mediastinal masses with cardiac involvement are of high risk for patients. Although rare, GISTs should always be considered. The union between Cardiology and Oncology is essential for the best treatment in these cases. 111924 Modality: E-Poster Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Comisa and Associated Cardiovascular Risk: A Case Report of a Successful Combined Intervention with Pap and CBTI MIGUEL MEIRA E CRUZ1, Ana Brito2, Verona Mihai3 (1) Sleep Unit, Centro Cardiovascular da Universidade de Lisboa, Lisbon School of Medicine, Lisbon, Portugal; (2) Guy's & St Thomas NHS Foundation Trust, London, UK; (3) Manchester University Foundation NHS Trust, London, UK Introduction: Insomnia and obstructive sleep apnoea (OSA) are the two most common sleep disorders globally, and co-exist in up to 50% of patients in clinic. The risk of cardiovascular and metabolic disorders (CMD) is often independently associated with insomnia and OSA, and such risk seems to be aggravated when these conditions are comorbid (COMISA). Recent data shows that collaboration of psychology and physiology-based Sleep Medicine strategies may help improve patient-centric care. Case description: 54 years old male patient with diagnosis of resistant hypertension, complaints of snoring and difficulties in initiating and maintaining sleep underwent sleep investigations in our department. The sleep study performed was consistent with the diagnosis of severe OSAS. The positive airway pressure (PAP) therapy was initiated and the patient was 100% compliant with the therapy. The response was excellent, with a residual Apnoea and Hypopnea Index (AHI) of 1.3/h and improved Epworth Sleepiness Scale from 11 to 5/24. Despite these good results, the patient still had problems initiating and maintaining sleep, presenting an Insomnia Severity Index (ISI) score of 13. He was at that point included in a Cognitive Behavioural Therapy program for insomnia (CBTI). After CBTI intervention, the patient presented a residual ESS of 4/21 and an ISI of 3, indicating no signs of clinical insomnia. The compliance with PAP remained excellent and the patient reported improvements on sleep quality, therapy management, as well as overnight awakenings. The blood pressure became normalised at 120/80 mmH2O. Conclusion: Despite the high co-morbidity and impact of COMISA, there are many unknowns concerning the pathophysiology and optimal therapeutic management of this condition. The optimal use of PAP and tailored CBTI showed significant results not only on resolving the OSAS and Insomnia but also by reduction of cardiovascular risk, with blood pressure being normalised. Therefore, the combination of sleep apnoea therapy and of behavioural sleep therapies, such as CBTI, can be the solution to address this complex condition. 111950 Modality: E-Poster Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Incidental Finding of Arrhythmogenic Right Ventricular Cardiomyopathy in 72-Year-Old Man - Should we Consider Cardio Defibrillator Implantation for Primary Prophylaxis? RAFAEL MODESTO FERNANDES1, Luciana Cunha Weber1, Vitor Queiroz de Castro Souza2, Loren Lacerda Rodrigues2, Mariana Baptista Guedes1 (1) D'Or Institute for Research and Education (IDOR), Hospital Alianca, Salvador, Brazil; (2) Bahiana School of Medicine and Public Health, Salvador, Brazil. Background: Described by Fountaine and Marcus in 1982, arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterized by progressive replacement of myocardial cells by fibrofatty tissue. This is a leading cause of sudden arrhythmic death in young people and athletes. Case: A 72-year-old man presented with heartburn, without relief after use of antacids. He denied chest pain, dyspnea, history of drinking or smoking. Past medical history was positive for stable coronary artery disease, non-specified arrhythmia, hypertension and hyperlipidemia. Physical examination was normal. The diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was established based on T wave inversions in inferior and anterior leads at electrocardiogram and an abnormal ultrasensitive troponin level. A pharmacological stent was placed in the mid-segment of the right coronary artery to treat a sub occlusive during the invasive coronary angiography. Transthoracic echocardiogram (TTE) revealed preserved left ejection fraction but severely compromised right ventricle (RV), not corresponding to angiography. Cardiac magnetic resonance imaging corroborated the findings of the TTE, segmental changes and RV aneurysms, in addition to the reduced RV ejection fraction. These findings were supportive of ARVC. Holter identified frequent ventricular premature beats, however without complex arrhythmias. After discussion with the Heart Team, the patient was classified as low risk, despite the important involvement of the RV. He was discharged and kept under outpatient follow-up without the need for implantable cardio defibrillators (ICD). Further screening was advised for family members. Discussion: Patients with ARVC usually present symptoms during the second to fifth decade of life. Advanced age poses a challenge for the diagnosis of the disease, as symptoms could be disguised as those of NSTEMI. In order to prevent misdiagnosis and improve risk stratification, more information is needed on the natural history of these patients. In this case, the decision to implant the ICD is challenging, considering the patient's age, degree of RV involvement and absence of complex arrhythmias. 112096 Modality: E-Poster Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM What are the Effects of Cardiovascular Rehabilitation on Exercise Tolerance, Fatigue and Quality of Life in Patients with Limiting Symptoms in the Post-COVID-19 Period in a Reference Service in Northeastern Brazil? DANIELLA CUNHA BRANDAO1, BRUNA THAYS SANTANA DE ARAUJO1, JULIANA ANDRADE FERREIRA DE SOUSA1, Maria Ines Remigio1, Armele Dornelas de Andrade1 (1) Universidade Federal de Pernambuco Introduction: The main limiting symptoms in the post-COVID-19 period are dyspnea, fatigue and reduced exercise tolerance. In these patients, cardiovascular rehabilitation can improve functional capacity, reduce deconditioning after a prolonged stay in the intensive care unit, and facilitate return to work. Objective: To verify the effects of cardiopulmonary rehabilitation consisting of aerobic and continuous resistance training of moderate intensity on pulmonary function, respiratory muscle strength, maximal and submaximal exercise tolerance, fatigue and quality of life in post-COVID-19. Methods: This is a quasi-experimental study with a protocol of 12 outpatient intervention sessions in a reference service for COVID-19 in Pernambuco. Adults over 18 years of age (N = 26) diagnosed with COVID-19 and discharged from hospital at least 15 days before the first assessment were included. Participants performed continuous moderate-intensity aerobic and resistance training twice a week. Maximum and submaximal exercise tolerance, pulmonary function, respiratory muscle strength, fatigue and quality of life were assessed before and after the intervention protocol. Results: Cardiopulmonary rehabilitation improved maximal exercise tolerance, with an increase of 18.62% in peak oxygen consumption (VO2peak) and 29.05% in time to reach VO2peak. The VE/VCO2 slope reduced by 5.21% after the intervention. We also observed an increase in submaximal exercise tolerance (increase of 70.57 meters in the 6-minute walk test, p = 0.001), improved quality of life and reduced perceived fatigue after the intervention. Conclusions: In this work, cardiopulmonary rehabilitation improved pulmonary function, respiratory muscle strength, maximal and submaximal exercise tolerance, fatigue and quality of life in patients with limiting symptoms in the post-COVID-19 period. Aerobic and continuous resistance training of moderate intensity proved to be effective in the recovery of these patients. 112015 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Treatment for Calcified Coronary Lesions using Intravascular Lithotripsy Assessed by FFR and OCT: Putting all Together LUIS AUGUSTO PALMA DALLAN1, Marcelo Harada Ribeiro3, Cristina Silveira3, Gabriel Tensol Rodrigues Pereira1, Guilherme Ferragut Attizzani1 (1) University Hospitals Cleveland Medical Center; (2) InCor - Instituto do Coracao - HCFMUSP; (3) SOS Cardio, Florianopolis, SC, Brazil Introduction: Patient 70 years old male caucasian, with multiple comorbidities, including hypertension, diabetes, obesity, dyslipidemia, CKD 3B (GFR 37, Creat 1.8), S/P prostate cancer, and severe AS (LVEF 55%, mean grad 50, Vmax 4.6, DI 0.19) with NYHA Class II symptoms including dyspnea with minimal exertion, worsening fatigue over the past 3 months, and intermittent chest pressure. In summary, the patient met indications for AVR. Coronary angiography pre-procedure showing a severely calcified lesion in proximal/mid/mid-distal LAD with angiographic moderate-to-severe lesions (60%). Per Heart Team discussion, elective FFR with possible PCI to LAD and elective TAVR. Procedure: In this case, assessment through FFR, OCT and Intravascular Lithotripsy contributed to simplify a potential high-risk procedure. FFR confirmed the severity distally to sequential lesions and indication for PCI. The images evidenced by OCT completely changed the patient's treatment. OCT was especially important to determine the anatomy of the lesion and adequate planning. Evidence of heavy proximal circumferential calcification and severe lesion in mid-distal LAD that would not be assessed through angiography. If the proximal lesion was not pre-treated, probably would have resulted in underexpansion of the stent with higher rates of stent failure. As per evidence of severe lesion in mid-distal LAD, it mostly would not be assessed only based on angiography. In addition, OCT also allowed for adequate treatment planning, with pre-dilatation and ideal stent sizing, with a satisfactory final result evidenced by excellent stent expansion and without signs of dissection of the stent edges. Intravascular Lithotripsy contributed to simplify a potential high-risk procedure such as a rotational atherectomy in proximal LAD in a patient with severe AS and no possibility of protected PCI with Impella due to severe aortic stenosis. Three days after discharge, the patient was submitted to elective TAVR successfully. Conclusion: We report the importance of physiology and intravascular imaging on a successfully OCT-guided PCI using intravascular lithotripsy: FFR confirmed the severity of the lesions and indication for PCI; OCT provided important information for adequate treatment planning and execution of the procedure, minimizing the risk of stent underexpansion; and Intravascular Lithotripsy contributed to simplify a potential high-risk procedure. 112041 Modality: E-Poster Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Holt Oram Syndrome Associated with Biventricular Non-Compaction Cardiomyopathy ERIVELTON ALESSANDRO DO NASCIMENTO1, Romero Ribeiro Duque2, Vinicius de Queiroz Aguiar2, Fabricio Vilhena de Castro Souza2 (1) Instituto Estadual de Cardiologia Aloysio de Castro - IECAC; (2) Centro Universitario de Volta Redonda - UniFOA Holt Oram Syndrome (HOS) is characterized by the presence of upper limb abnormalities associated with cardiac malformations and cardiac conduction disorders, being an autosomal dominant hereditary disease, present in 1 in 100.000 individuals. Cardiac malformations, in general, are related to defects in the septation of the heart, with interatrial communication ostium secundum and interventricular communication being the most common. Non-Compaction Cardiomyopathy (NCC) is a rare condition characterized by increased trabecculation in one or more segments of the ventricles, especially the left ventricle. NCC can be found isolated or related to multiple phenotypes of cardiac structural alterations and arrhythmogenic alterations, however, the association with HOS presents a low number of case reports in the literature. We report a case of HOS associated with biventricular NCC. A 17-year-old male student with HOS and deformities in both upper limbs and previous atrioseptoplasty, was referred to the arrhythmology ambulatory complaining of "weak beats" and suspected NCC after performing a transthoracic echocardiogram. In the evaluation by the specialist, the patient had a heart rate between 42 and 45 beats per minute, and a 24-hour Holter and cardiac MRI were requested to assess bradycardia and suspicion of NCC. The 24-hour Holter presented periods of atrioventricular dissociation with bradycardic junctional escape. MRI showed increased endocardial trabeculate in the right ventricle and increased subendocardial trabeculation in the left ventricle (LV), with diagnostic impression of LV dilation associated with criteria of non-biventricular compaction, with preserved systolic function and absence of local fibrosis. Given the diagnosis of bi-ventricular NCC, the patient is followed up by the arrhythmology ambulatory to evaluate bradycardia with serial examinations. HOS associated with NCC presents a reduced number of reports in the literature, with presentations commonly affecting only the left ventricle. Thus, the case reported describes a patient diagnosed HOS related with bi-ventricular NCC, manifesting with atrioventricular blockade. 112175 Modality: E-Poster Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Super Response in Resyncronization with Direct Left Bundle Branch Stimulation and Right Ventricle Depolarization Delay Correction. Case Report RAONI DE CASTRO GALVAO1, Joao Paulo Velasco Pucci1, Ofir Gomes Vieira1, Edvagner Sergio Leite de Carvalho1, Carlos Eduardo Duarte2 (1) Centro de Ritmologia de Brasilia; (2) CARE: Centro Avancado de Ritmologia e Eletrofisiologia; (3) Hospital Santa Lucia Cardiac resynchronization (CRT) has been an established procedure for over 20 years. Recently, direct stimulation of the cardiac conduction system has been gaining strength. Recent studies already show them with results similar to traditional CRT. We report a case submitted to CRT with direct stimulation of the left bundle branch followed by correction of the right ventricular depolarization delay with stimulation of its region with the greatest delay, in inferior wall activation. Case Report: Female 77y, idiopathic cmp, LVEF 23%, increased LV diameters, diffuse hypokinesia and absence of fibrosis in the LV walls. ECG with LBBB and QRS 170 ms. Evolved with decompensated HF, recent hospitalizations. After clinical compensation, a CRT was implanted on 04/2021. First ventricular lead was implanted in the deep interventricular septum, after mapping the HIS bundle. During threshold test, there was selective stimulation of the LBB, with a RBBB morphological QRS, axis at 80deg and width of 130 ms. By direct pacing of the left bundle branch, we took advantage of the other ventricular lead to correct the RV conduction delay generated by LBB pacing. After finding a delay of 90 ms, we chose to fix the second ventricular lead in the inferior wall of RV. Joint ventricular pacing resulted in a QRS of 108 ms, QRS axis -20deg. Transthoracic echocardiogram at 45 days post-op showed an increase in LVEF to 48%, LV dimensions at 55/40 mm. At the moment the patient remains in NYHA-I. A 6 month ECHO-TT showed a LVEF 54% and preserved LV dimensions, patient remaining in NYHA-I. Discussion: This report proposes a RV-CRT to correct a RBBB QRS morphology generated by direct stimulation of the LBB. About 30% with CRT are non-responders. Whether due to a non-ideal LV lead position, unfavorable coronary sinus anatomy, phrenic stimulation, etc. In this sense, CRT by direct stimulation of the HIS-purkinje system corrects many adversities in a simpler procedure to be performed. In this case, complete correction of previous LBBB encouraged us to use the other electrode to correct the RV activation delay generated by the LBB stimulation, resulting in a narrower QRS, allowing clinical response and an important and early LVEF increase. This report corroborates the literature by showing that stimulation of the conduction system is a real alternative to patients with indication for CRT. 112185 Modality: E-Poster Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Coronary Intervention for Ostial Right Coronary Artery Chronic Total Occlusion using Rotational Atherectomy Through the Subintimal Space LUIS AUGUSTO PALMA DALLAN1, Luis Augusto Palma Dallan2, Cristina Silveira1, Carlos Augusto Campos2, Michael Megaly3 (1) SOS Cardio, Florianopolis, SC, Brazil; (2) InCor - Instituto do Coracao - HCFMUSP, Sao Paulo, SP, Brazil; (3) Department of Cardiology, Willis Knighton Heart Institute, Shreveport, Louisiana, USA A 78-year-old man with previous coronary artery bypass surgery (CABG) 10 years ago presented for right coronary artery (RCA) chronic total occlusion (CTO) percutaneous coronary intervention (PCI) for medical refractory angina after prior failed attempt. Coronary angiogram patent vein grafts to left anterior descending (LAD) and ramus arteries with early septal collaterals to occluded RCA . RCA occlusion was ostial and severely calcified . After crossing the Fielder XTa wire (Asahi Intecc, Japan), the lesion could not be crossed with different balloons or microcatheters. Therefore, we knuckled a RotaWire floppy (Boston Scientific, USA) subintimally beyond the proximal cap and performed rotational atherectomy (RA) with 1.25 mm followed by 1.5 mm burrs at 180,000 rpm . We then could advance a Finecross microcatheter (Terumo, Japan) along with a Pilot 200 wire (Abbott vascular, USA). We then crossed retrograde through septal collaterals and performed guide-extension assisted reverse controlled antegrade-retrograde dissection tracking and reentry (reverse CART) followed by completion of PCI and good final angiographic result . Hospital stay was uneventful and the patient was free from angina at 6-month follow-up. Our case describes the modification of ostial CTO lesions with RA after DR, which has not been described before. Calcification remains one of the major challenges during CTO PCI.1 Different modalities can be used to modify calcium including RA. RA use after dissection-reentry (DR) techniques within the main vessel have been previously reported, but still carries a very high-risk of perforation and is advised against. The implementation of DR techniques has played a key role to make possible wire crossing even in severe calcified occlusions and increase the overall success rate. Although with DR, the pathway is easier as you go around calcium, the vessels might remain non-compliant requiring calcium modification. For ostial modification of CTO lesions after DR techniques, the authors recommend using high-speed (180,000 rpm) with very short runs and mainly in straight segments. Our technique represents a bailout strategy after failure of other techniques. It still carries a high risk of perforation or aortic dissection and benefits should outweigh the risks when making the decision to proceed. 112316 Modality: E-Poster Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Vasospasm and Acute Coronary Syndrome NATHALIA DUARTE CAMISAO1, MIGUEL ANGELO RIBEIRO1, ANDRE PAZOS TEIXEIRA1, NATALIA DOMINGUEZ PAES LEME DE SOUZA1, JOSE HERBERT DA SILVA PALHANO1 (1) Hospital Norte D'or Introduction: Vasospastic angina is a variant form of angina pectoris in which angina occurs at rest with transient changes in the electrocardiogram and exercise capacity preserved. It is involved in many clinical scenarios such as stable angina, sudden death, acute coronary syndrome, arrhythmia or syncope. Smoking is a well-known precipitating factor in this clinical setting. Case Report: Male patient, 58 years old, systemic arterial hypertension, smoker (smoking history 25 years - pack), in outpatient follow-up due to long-standing chest pain but with significant worsening in the last two months. Transthoracic echocardiogram (TTE) with preserved left ventricular systolic function, no segmental changes, no intracavitary overloads. Electrocardiogram with alteration of repolarization in the antero septal wall. Myocardial scintigraphy without perfusion changes, without ventricular dysfunction. Guided lifestyle changes and smoking cessation. Admitted to the ER 6 months later with oppressive chest pain radiating to the left upper limb, profuse sweating, associated with dynamic ST-segment change in the high lateral wall and increase in myocardial necrosis markers (ultrasensitive troponin peak of 38520 ng/L). He continued smoking. TTE similar to that performed previously, without significant changes. Coronary angiography was performed: significant vasospasm in the circumflex artery reversed after nitroglycerin, no obstructive lesions, ventriculography with infero apical hypokinesia. A calcium channel blocker was introduced with good clinical evolution without a new episode of chest pain during hospitalization. Conclusions: Although the pathogenesis of coronary artery spasm has not been fully elucidated, different pathogenic mechanisms have been proposed, such as vascular smooth muscle cell hyperreactivity, endothelial dysfunction, vascular inflammation, altered autonomic nervous system response, and oxidative stress. These variables can be modified if it's possible to detect early precipitating factors such as smoking in this case. 107810 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Late Follow-Up of Patients with ST-Elevation Myocardial Infarction Treated by Pharmaco-Invasive Strategy MARINA PASSOS PIZZITOLA1, Vinicius Nasser de Carvalho1, Pedro Luiz Homem de Mello1, Paula Santiago Teixeira1, Jose Roberto Pineda Pietrobon Redini Martins1, Filippo Mancini Diotto1, Bruna Regina Cogo1, Adriano Henrique Pereira Barbosa1, Iran Goncalves1, Pedro Ivo de Marqui Moraes1 (1) Universidade Federal de Sao Paulo - Unifesp Introduction: The risk of new cardiovascular events after an episode of ST elevation myocardial infarction (STEMI) conditions patients to a high-risk profile and reinforces the need to expand epidemiological knowledge about the long-term follow-up in this group. Objectives: To evaluate the rates of all-cause and cardiovascular mortality, reinfarction and ischemic stroke in the late follow-up of STEMI patients treated by the pharmaco-invasive strategy (PhIS). Methods: Data from a county network for the treatment of STEMI from January-2016 to December-2019 were analyzed, containing 1,170 consecutive patients undergoing fibrinolysis (97% tenecteplase) in county hospitals and systematically transferred to the tertiary center for cardiac catheterization and continuity of care, according to the PhIS. Post-discharge follow-up was performed on an outpatient basis or via telephone call to those who were absent, with approval by the institutional Research Ethics Committee. Numerical variables were described as median and interquartile range. Results: The baseline demographic profile of the 1,170 patients evaluated was 348 (29.7%) women, age 59 [51-66] years, 654 (55.9%) hypertensive, 324 (27.7%) diabetics, left ventricular anterior wall infarction in 559 (47.8%), door-to-needle time of 68 [41-110] minutes and fibrinolytic-catheterization time of 16.5 [7.3-23.1] hours. In-hospital mortality was 60 (5.1%) cases. Loss of post-discharge follow-up occurred in 251 (21.4%) patients who were not located, so 919 were analyzed with a median follow-up of 2.6 [1.7-3.2] years. The overall mortality rate was 50 (5.4%), with 34 of the deaths (68.0%) attributable to cardiovascular causes, and the rates of reinfarction and ischemic stroke were respectively 56 (6.1%) and 15 (1.6%). Conclusion: Although the elevated loss of follow-up constitutes a limitation for the analysis, patients from a county network for the treatment of STEMI based on PhIS had a high risk of recurrence of cardiovascular outcomes. 110502 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Spatiotemporal Distribution of the Mortality of Coronary Arterial Disease Amongst Women in the State of Parana/Brazil between 2008 and 2017 GIOVANNA MENIN DA SILVA 2, Marcelo Aguilar Puzzi1, Luciano de Andrade1, Amanda de Carvalho Dutra1 (1) Universidade Estadual de Maringa; (2) Universidade Federal de Sao Paulo Coronary artery disease (CAD) remains the leading cause of death in women. The negative impact of CADs can be reduced through preventive care with interventions that address from the population to actions that have an individual character. Thus, combining information regarding the occurrence of CAD in women with the spatiotemporal variation constitutes an instrument that enables the development of strategies to identify areas of greater risk for developing the disease, the increase in risk over time and proposition of policies that favor interventions to reduce morbidity and mortality. Objective: To analyze the spatiotemporal distribution of mortality rates of adult women with CAD in the State of Parana - Brazil from 2008 to 2017. Methodology: This is a descriptive, observational, retrospective study with the purpose of analyzing the spatiotemporal distribution of inequalities, with the use of geospatial health statistics, based on secondary mortality data in this period. Results: There is a correlation between the annual and spatiotemporal rates, demonstrating that the analyzed covariates lead to municipal inequalities, mainly, income, education and access to a medical specialist, showing that comprehensive health care can disadvantage the survival of these patients. SMR greater than 1, correlates with higher income (p = 0.381), higher education index (p = 0.056), higher health index (p = 0.115), higher number of cardiologists (p = 0.232), higher rate of exercise test (p = 0.056) is considered high risk, corresponding to 75%, 50%, 25%. The correlation between greater accessibility, greater number of cardiologists, greater exercise testing and greater health index in Parana with 75% of a SMR with greater risk. Conclusion: Public health policies that serve everyone with equity, observing their loco-regional particularities should be encouraged and taken as a goal in the management of conflicts that affect women unequally. 107823 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING DNA Damage Induced by Ionizing Radiation from Myocardial Perfusion Scintigraphy: A Real Threat? ANNA PAULA ARPINI BOTELHO1, Julia Passarelli Pereira1, Raiana Andrade Quintanilha Barbosa1, Aniele Moritz1, Marcelo Goulart2, Glauber Monteiro Dias1, Andrea De Lorenzo1 (1) Instituto Nacional de Cardiologia Background: Patient exposure to ionizing radiation has grown due to increases in medical imaging, raising concern about potential risks. Among cardiac imaging tests, myocardial perfusion scintigraphy (MPS) is vastly employed. Overall, the link between radiation from MPS and cancer has not been considered consistent; however, further evidence obtained from studies at the molecular level is desirable. Objective: To study the effect of ionizing radiation on the DNA of patients undergoing MPS using the comet assay, a method for detection of DNA damage, and the activation of repair genes in response to potential DNA damage. Methods: Twenty-nine patients >=18 years without acute diseases, recent surgery, cancer or autoimmune diseases were studied. MPS was performed with Tc-99 sestamibi (15-20 mCi) in a 2-day protocol. Peripheral blood was collected immediately before radiotracer injection at rest and 60-90 minutes after injection for the analyses. Single-cell gel electrophoresis (comet assay) was performed with blood lymphocytes to detect strand breaks, which determine a "comet tail" of variable size, visually scored by 3 observers in a fluorescence microscope after staining (0: no damage, no tail; 1: small damage; 2: large damage; 3: full damage). A damage index was calculated as a weighted average of the individual scores. The expression of repair genes CDKN1A, BBC3, XPC, GADD45a was evaluated with RT-PCR (QuantStudio 5, Thermo Fisher Scientific). Results: After radiotracer injection, there was a significant, although small, increase of the damage index and of classes 1-3 of damage, even though most patients remained in class 0 . There was no significant difference in the expression of CDKN1A, BBC3, XPC, GADD45a after radiotracer injection . Conclusion: DNA damage was detected in lymphocytes after a single radiotracer injection for MPS, without activation of repair genes. This suggests that MPS with the current protocols may not result in relevant DNA damage. 107829 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Evaluation Electrocardiographic in Rats Infected with Plasmodium Falciparum and Submitted to Phytotherapy with Ammbaka CUSTODIO JOSE GASPAR1, Miracelma de Assuncao Pedro Alexandre1, Amelia Carlos Cazalma1, Jordao Augusto Trajanno2, Luciano Julio Chingui1 (1) Universidade Metodista de Angola (UMA); (2) Casa de Caminho Andre Luis Introduction: Malaria is a multisystem, non-contagious infectious disease caused by protozoa of the species Plasmodium falciparum, vivax, P. maleriae, P. ovale Stephens. Worldwide, malaria is characterized as the main cause of morbidity and mortality, in Angola malaria is caused mainly by Plasmodium falciparum, that is, 87% of cases. Objectives: The objective of the present work is to evaluate and describe the effect of AMBAKA on the biological system of albino rats infected with Plasmodium falciparum. Material and methods: This is an experimental/animal study, developed at the Methodist University of Angola. Eighteen male albino rats, aged 3 to 4 months, were used. The animals were divided into 3 experimental groups of n = 6: Control group, malaria and malaria treated with Ammbaka. For the induction of malaria in animals, human blood infected with the protozoan Plasmodium Falciparum was used. Each animal received an intraperitoneal injection of 0.05 ml of infected blood. 15 days after infection, microscopy was performed to evaluate parasitemia, for treatment, Ammbaka was used for 3 consecutive days, each animal received a dose of 0.7 ml intraperitoneally. On the fourth day, microscopy was performed to assess the absence of the parasite. The results were submitted to the Kolmogorov-Smirnov normality test, followed by ANOVA and post Tukey test with a significance level of 5% (p < 0.05). Results: The results reveal that the animals developed malaria and Ambaka was able to eliminate plasmodium falciparum, the animals with malaria developed incomplete left bundle branch block, acute myocardial infarction and right atrial overload, both the malaria and the malaria group treated with Ammbaka caused insulin resistance, Ammbaka caused a reduction in adipose tissue. Conclusion: The proposed protocol was efficient for inducing malaria, Ammbaka can be used as a therapeutic model for malaria, Ammbaka did not change cardiac contractility, Ammbaka generated metabolic disturbance and depreciated the weight of periepididymal fat. The study revealed that malaria significantly compromises the functionality of the heart muscle, as these changes found can lead to death. 111453 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSICAL EDUCATION Longitudinal Associations of Physical Inactivity, Overweight and Obesity with the Development of Cardiometabolic Multimorbidity: A Nationally Representative Cohort Study WILLIAM YANG ZHAO1, Li He2 (1) The George Institute for Global Health, China; (2) College of Physical Education and Sport, Beijing Normal University, China Background: Cardiometabolic multimorbidity is increasingly common and is associated with adverse health outcomes. Physical inactivity and obesity are associated with poor health and psychological well-being. This study aims to identify the longitudinal associations of physical inactivity, overweight and obesity on the development and worsening of cardiometabolic multimorbidity over time. Methods: Using a four-wave nationally-representative sample from the China Health and Retirement Longitudinal Study, we analyzed 17,708 participants >=45 years with and without cardiometabolic multimorbidity. The development of Cardiometabolic multimorbidity was measured as the accrual of additional conditions over an 8-year period. Poisson-distributed Generalized Linear Models (GLM) were used to estimate the association of cardiometabolic multimorbidity with physical inactivity, overweight and obesity. Results: 22.48% of included participants had cardiometabolic multimorbidity at baseline and 35.28% at follow-up. 4,102 of 9,927 (41.32%) participants without multimorbidity and 819 of 2,879 (28.45%) with existing multimorbidity developed new condition/s. Physical inactivity was significantly associated with cardiometabolic multimorbidity (relative risk [RR] = 1.254, confidence interval [CI]: 1.136-1.385), complex multimorbidity (RR = 1.614, CI: 1.348 1.933), and worsened multimorbidity (RR = 1.214, CI: 1.032-1.427). Overweight & obesity was also significantly associated with cardiometabolic multimorbidity (RR = 1.705, CI: 1.574-1.846), and complex multimorbidity (RR = 2.156, CI: 1.852-2.510), and worsened multimorbidity (RR = 1.385, CI: 1.217-1.576). Conclusion: Physical inactivity, overweight and obesity are associated with the development and worsening of cardiometabolic multimorbidity over time. They support the recent National Institute for Health & Care Excellence (NICE) Guidance on multimorbidity that suggests that patients with multimorbidity should be identified and targeted for interventions to improve health outcomes. 107888 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Effect of Colchicine use on Inflammatory Markers, Myocardial Injury and Pain Control in the Postoperative of Heart Surgery Patients: A Study Conducted in a High-Complexity Cardiovascular Hospital in Southern Brazil ALLANA MAYCHAT PEREIRA OLIVEIRA1, Barbara Swarowsky Tabach2, Leonardo Silveira Nascimento1, Dannuey Machado Cardoso3, Silvio Augusto Ortolan1, Lara de Matos1, Julia de Moraes Costa2, Francisco Coelho Lamachia1, Caroline Brand2, Lester Krann Motta1, Leonardo Dorneles de Souza1, Dulciane Nunes Paiva2 (1) Hospital Santa Cruz. Santa Cruz do Sul, RS, Brazil; (2) Universidade de Santa Cruz do Sul. Santa Cruz do Sul, RS, Brazil; (3) Centro de Ensino Superior Dom Alberto. Santa Cruz do Sul, RS, Brazil Introduction: Coronary artery bypass grafting is the most frequently used cardiac surgery (CS) for the treatment of symptomatic coronary artery disease. Because this is a major surgery, it is related to an increase in the inflammatory response in the postoperative (PO) period. Pain is one of the main complications of sternotomy. Objective: To verify the effect of colchicine on inflammatory markers, myocardial injury and pain control in the PO of CS. Methods: Randomized, double-blind, placebo-controlled clinical trial, carried out in a high-complexity cardiovascular hospital in southern Brazil. Patients undergoing CS and admitted to the intensive care unit (ICU) were evaluated. Patients of both genders, aged between 18 and 45 years and hemodynamically and neurologically stable, were included. The exclusion criteria were: emergency CS, patient with pacemaker, need for antibiotic therapy, presence of atrial fibrillation in the preoperative period and renal failure. Pain perception was assessed using the Visual Analogue Scale and troponin and C-reactive protein (CRP) levels. The patients were randomized into a control group, which received placebo, and a colchicine group, which received 0.5 mg 1x/day if body weight was up to 70kg or 0.5 mg 2x/day if body weight was over 70kg. Colchicine and placebo were administered preoperatively, restarted in the PO, and continued until outpatient reassessment (30 days after the CS). Patients were evaluated preoperatively, in the immediate PO, in the late PO (before discharge from the ICU) and 30 days after the CS. Results: The sample consisted of 43 patients (24 males and 19 females), of which 21 were allocated to the colchicine group and 22 to the control group. The mean age of the colchicine group was 63.9 years (+-2.9) and 63.4 years (+-3.0) in the control group. There was no statistical difference between the groups regarding variance in troponin, CRP levels and pain perception in the four assessments. However, in the analysis of individual prevalence, the colchicine group had 51.6% of respondents in relation to the decrease in CRP levels, which was observed in 48.4% of the control group. Conclusion: There was a higher individual prevalence of responders to colchicine on CRP levels compared to individuals who received placebo, with no difference in the prevalence of responders between the groups regarding myocardial injury markers and pain control in the PO of CS. 107849 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality from Heart Failure in the Elderly in Brazil: Temporal Trend Analysis from 2013 to 2019 NATANAEL ALVES DE LIMA1, Natanael Alves de Lima1, Thiago Emanuel Rodrigues Novaes2, Eduardo Pitthan2 (1) Universidade Federal da Fronteira Sul; (2) Universidade Federal da Fronteira Sul Introduction: Heart Failure (HF) is a complex clinical syndrome and represents the final stage of the natural history of heart diseases of multiple etiologies. The increase in survival has impacted the exponential increase in the elderly population. The elderly in Brazil have a high rate of incidence and prevalence of HF, morbidity and mortality and hospitalization, demanding pressure and high costs in the Brazilian Health System. Objective: To evaluate the trend of variation in crude mortality rates from HF in the elderly in Brazil, comparing age groups. Methods: Refers to an ecological, descriptive and quantitative study that used data available on DATASUS ) on March 8, 2022 referring to to mortality in the elderly due to HF, in Brazil, from 2013 to 2019, divided into two age groups: 60 to 79 years and 80 years or older. Crude mortality rates were calculated in these variables per 100,000 inhabitants, based on the population variation in Brazil in the years chosen for the study, made available by the IBGE ) in a consultation carried out in 08 March 2022. Results: The analysis of mortality from HF over 60 years, in 2013, showed a rate of 55.7/105 inhabitants, and showed a small drop in 2019, being 51/105 inhabitants. Making a drop of 8.4% per 105 inhabitants. On the other hand, in the same period the population of this age group increased by 94.4%. The analysis of mortality due to HF over 80 years, in 2013, showed a rate of 60.9/105 inhabitants and showed a small drop in 2019, making a drop of 1.5%. On the other hand, in the same period, the age population increased by 95.3%. Conclusion: The results of this study demonstrate that there has not been a significant change in the mortality rate from HF in the elderly in Brazil in recent decades. The trend is more pronounced in the range above 60 to 79 years. 108558 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Effects of Euterpe Oleracea Mart. (Acai) on Platelet Aggregation in Healthy Individuals WANDA VIANNA MURY1, Wanda Vianna Mury1, Mariana Siqueira de Medeiros1, Marcela Anjos Martins1, Claudia de Morais Sequeira1, Angela de Castro Resende1, Cristiane Matsuura1 (1) Universidade do Estado do Rio de Janeiro Introduction: Euterpe oleracea Mart. (acaizeiro) is a plant typical from Brazil, rich in polyphenols, which has vasodilator properties, prevents endothelial dysfunction and improves metabolic profile. However, its role on platelet function is not known. Platelets are essential for the maintenance of vascular hemostasis, but they may also participate in thrombus formation when hyperactivated, contributing to the pathogenesis of ischemic diseases. Thus, the objective of this study was to investigate the effects of acai stone hydroalcoholic extract (ASE) on platelet aggregation. Methods: The blood from 15 healthy young men was collected, centrifuged and the isolated platelets were incubated with 10, 50 or 100 mg/mL ASE for 15 min (according to each experiment). Platelet aggregation was measured in platelet-rich plasma (PRP) and whole blood. In order to assess the effects of ASE on the platelet inhibitor nitric oxide (NO), we measured cGMP levels. Additionally, cAMP levels were quantified, the second messenger of platelet inhibitor prostacyclin. To compare the different ASE concentrations, the one-way ANOVA test with repeated measures was used. In case of significant F, a Holm Sidak post-test was performed. When only one concentration of ASE was tested, the paired t-test was applied. Statistical significance was considered when p <= 0.05. Results: ASE inhibited collagen-induced PRP aggregation induced by collagen (baseline, 82.7 +- 5.6, ASE50, 54.0 +- 7.2, ASE100, 31.4 +- 4.1%, p < 0.0001), ADP (baseline, 46.1 +- 7.5, ASE50, 32.1 +- 4.1, ASE100, 17.6 +- 2.6%, p < 0.0001) or thrombin (baseline, 103.4 +- 4.5, ASE 50, 77.2 +- 8.9, ASE100, 53.4 +- 7.1%, p = 0.0002), as well as in whole blood under stimulation with collagen (baseline, 28.0 +- 4.0, ASE50, 19.6 +- 4.4, ASE100, 14.8 +- 2.5 O, p = 0.008). ASE increase cGMP levels (baseline, 0.67 +- 0.19, ASE50, 1.50 +- 0.39, ASE100, 1.64 +- 0.49 pmol/108 cells, p = 0.020). Similarly, there was an increase in cAMP levels (baseline, 9.8 +- 1.8, ASE50, 13.9 +- 2.3, ASE100, 15.3 +- 2.6 pmol/108 cells. Concluison: These results indicate that ASE has a potent inhibitory effect on platelet aggregation. In this way it is possible that ASE has the potential to be used in the prophylaxis and treatment of diseases associated with platelet hyperaggregability, although the mechanisms underlying this process need to be fully clarified. 107969 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Long Term Prognostic Value of Troponin Elevation on Admission After Hospitalization for COVID-19 GABRIEL SALIM SAUD DE OLIVEIRA 1, Joao Roquette Fleury da Rocha1, Barbara Mariz Ferreira Passos1, Ismael Magalhaes Matos de Faria1, Ana Carolina Rodrigues Lado1, Ricardo Antonio Correia Lima2, Pedro Paulo Nogueres Sampaio2, Juliano Carvalho Gomes de Almeida1, Joao Mansur Filho2, Roberto Muniz Ferreira1, Lucia Helena Alvares Salis1, Nelson Albuquerque de Souza e Silva1 (1) Federal University of Rio de Janeiro, Edson Saad Heart Institute, Brazil; (2) Samaritano Hospital, Botafogo, Rio de Janeiro, Brazil Introduction: Several biomarkers have demonstrated prognostic value in patients with Coronavirus Disease-2019 (COVID-19), primarily during hospitalization. Troponin I (TnI) has been widely studied in this context, though its association with outcomes after the initial hospitalization period remains unknown. Objectives: To determine the association between high sensitivity TnI elevation above the 99th percentile upper reference limit on admission in hospitalized patients with COVID-19 and long term survival among those who were successfully discharged. Methods: Medical records from consecutive patients with confirmed COVID-19 admitted to a single institution between March and July 2020 were retrospectively analysed. Clinical data and TnI values were collected and correlated with long term mortality after the index hospitalization. Results: Among 230 patients, 194 survived until hospital discharge, of which 149 had TnI values on admission and were included in the analysis. Median age was 65 years (52-78) and 56.4% were male. Cardiovascular disease (CVD) was present in 12%, and 36.2% were treated in the intensive care unit (ICU). Troponin elevation occurred in 21 patients (14.1%), and 9 (6%) died after a median follow up of 631 days (612-643). Troponin was associated with death in the univariate (OR 16.7; 95% CI 3.8-73.6, p < 0.001) and multivariate analyses (OR 8.6; 95% CI 1.5-49.6, p = 0.02), after adjusting for age, previous CVD, ICU admission, C-reactive protein and creatinine values. Figure 1 represents the Kaplan-Meier survival estimates after hospital discharge according to TnI elevation. Conclusions: Although most patients have a favourable outcome after hospitalization for COVID-19, cardiac injury on admission appears to remain predictive of long term survival after discharge. 107978 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Validation of the Grace Risk Score to Predict In-Hospital and 6-Month Post-Discharge Mortality in Patients with Acute Coronary Syndrome VITOR BONIATTI NEVES1, Vitor Boniatti Neves1, Raquel Melchior Roman2, Tiago Vendruscolo2, Gilberto Heineck2, Carlos Alberto Santos de Mattos2, Eduardo Ilha de Mattos2, Luiz Carlos Pereira Bin1, Karine de Lima Sirio Boclin3, Marcelo Fialho Roman1 (1) Faculdade Meridional (IMED), Passo Fundo, RS - Brazil; (2) Hospital de Clinicas de Passo Fundo (HCPF), Passo Fundo, RS - Brazil; (3) Universidade Estacio de Sa (UNESA), Rio de Janeiro, RJ - Brazil Background: The wide range of clinical presentations of acute coronary syndrome (ACS) makes it indispensible to use tools for risk stratification and for appropriate risks management; thus, the use of prognosis scores is recommended in the immediat clinical decision-making. Objective: To validate the Global Registry of Acute Coronary Events (GRACE) score as a predictor of in-hospital and 6-month post-discharge mortality in a population diagnosed with ACS. Methods: This is a prospective cohort study of consecutive patients diagnosed with ACS between May and December 2018. GRACE scores were calculated, as well as their predictive value for in-hospital and 6-month post-discharge mortality. The validity of the model was assessed by two techniques: discriminative power using the area under the receiver operating characteristic curve (AUC) and goodness-of-fit, using the Hosmer-Lemeshow (HL) test, at the 5% level of significance. Results: A total of 160 patients were included, mean age 64 (+-10.9) years; of which 60% were men. The risk model showed to have satisfactory ability to predict both in-hospital mortality, with an area under the curve (AUC) of 0.76 (95% confidence interval [CI], 0.57-0.95; p = 0.014), and 6-month post-discharge mortality, with AUC of 0.78 (95%CI, 0.62-0.94), p = 0.002. The HL test indicated good-fit for both models of the GRACE score. Conclusion: In this study, the GRACE risk score for predicting mortality was appropriately validated in patients with ACS, with good discriminative power and goodness-of-fit. The results suggest that the GRACE score is appropriate for clinical use in our setting. 108053 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality from Diseases of the Circulatory System in Brazil and its Relationship with Social Determinants Focusing on Vulnerability LUIZ ANTONIO VIEGAS DE MIRANDA BASTOS1, Luiz Antonio Viegas de Miranda Bastos1, Jose Lucas Peres Bichara1, Paolo Blanco Villela1, Gabriela da Silva Nascimento1, Glaucia Maria Moraes de Oliveira1 (1) Universidade Federal do Rio de Janeiro UFRJ Introduction: Deaths from diseases of the circulatory system (DCS) and ischemic heart diseases (IHD) are declining, but slowly in developing countries, emphasizing its probable relationship with determinants of social vulnerability. Objectives: To analyze the temporal progression of mortality rates of DCS and from 1980 to 2019 and the association of the rates with the Municipal Human Development Index (MHDI) and Social Vulnerability Index (SVI) in Brazil. Methods: We estimated the crude and standardized mortality rates of DCS and IHD and analyzed the relationship between the obtained data and the MHDI and SVI. Data on deaths and population were obtained from the. The MHDI and the SVI of each federative unit were extracted from the websites Atlas Brasil and Atlas da Vulnerabilidade Social, respectively. Results: The age-standardized mortality rates of DCS and IHD showed a downward trend nationwide, which was unequal across the federative units. There was an inversely proportional relationship between the standardized mortality rates of DCS and IHD and the MHDI. The downward mortality trend was observed when the indices were greater than 0.70 and 0.75, respectively. The SVI was directly proportional to the standardized mortality rates of DCS and IHD. An upward mortality trend was observed with an SVI greater than 0.35. Conclusion: Social determinants represented by the MHDI and the SVI were related to mortality from DCS and IHD across the Brazilian federative units. The units with most development and least social inequalities had the lowest mortality from these causes. The most vulnerable die the most. 108060 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Methotrexate Associated with Lipid Nanoparticles Prevents Interstitial Fibrosis of the Left Ventricle in Spontaneously Hypertensive Rats ALINE DE OLIVEIRA SILVA1, Maria Carolina Guido1, Mauricio Tavares Costa1, Natalia de Menezes Lopes1, Amanda de Almeida Silva1, Priscila Oliveira Carvalho1, Raul Cavalcante Maranhao1 (1) Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, SP, BR. Background: Systemic arterial hypertension is a major risk factors for cardiovascular diseases. Interstitial fibrosis is directly associated with ventricular dysfunction in spontaneously hypertensive rats (SHR). Incorporation of methotrexate (MTX), a folic acid inhibitor, into lipid nanoparticles (LDE) increases cellular uptake and decreases MTX toxicity. LDE-MTX showed potent anti-inflammatory and anti-proliferative effects in rabbits with atherosclerosis and rheumatoid arthritis. In rats submitted to acute myocardial infarction, LDE-MTX reduced infarct size and left ventricular (LV) dysfunction. Aim: To investigate the effect of LDE-MTX treatment on the prevention of cardiac remodeling that occurs in SHR rats. Methods: Three groups of 6-week-old male rats were studied: 1) Control (CT, n = 8), Wistar-Kyoto rats weekly treated with I.P injection of saline solution; 2) SHR-LDE (n = 8): SHR rats treated with injection of LDE only and 3) SHR-LDE-MTX (n = 8): SHR rats treated with LDE-MTX (1 mg/kg intraperitoneally, weekly, for 20 weeks). After the treatment period, echocardiography was performed and the animals were euthanized for LV morphometry and protein expression by Western blot. Results: Compared to CT, SHR group presented LV dilation, represented by increase in systolic and diastolic diameters; cardiac hypertrophy due to increased LV posterior wall thickness and relative heart weight. SHR also had reduced ejection fraction and LV shortening, indicating LV systolic dysfunction. In SHR-LDE, there was increase in collagen content in the interstitial region of the LV, possibly resulting from an increase in type 1 collagen, which indicates increase in fibrosis of LV. LDE-MTX had no effect on LV dilation, cardiac hypertrophy or LV systolic dysfunction in SHR rats. However, LDE-MTX decreased LV interstitial fibrosis. In order to identify possible mechanisms associated with LDE-MTX and the reduction of interstitial fibrosis, we quantified the expression of angiotensin II receptors type 1 (AT1) and 2 (AT2) in the LV of the animals. However, there was no difference in the expression of AT1 and AT2 between the 3 groups. Conclusion: LDE-MTX treatment reduced LV interstitial fibrosis in SHR rats, possibly by reducing type 1 collagen expression, despite having no effect on LV systolic dysfunction. It is possible that the reduction in LV fibrosis achieved by treatment with LDE-MTX reduces the damage of hypertension on cardiac function when the animal reaches more advanced. 108092 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOGERIATRICS Atrial Fibrillation and Hospital Mortality in Octogenary Patients Included in the Sepsis Protocol from January 2018 to December 2020 MICHELE OURIQUES HONORATO1, Juscelio Trajano de Souza Filho1, Luiz Frederico Bezerra Honorato Junior1, Nathalia Watanabe1, Gabriela Machado Goulart2 (1) Hospital Sirio Libanes; (2) Universidade do Extremo Sul Catarinense Introduction: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting about 2 to 4% of world population, and in patients hospitalized in intensive care units, this incidence can go up to 23%. Advanced age is a risk factor for the development of AF, and those above 80 years of age become more susceptible to its deleterious effects. The impact of AF in septic patients is reflected in worse clinical outcomes and the identification of the triggering factors can be a target of future prevention and treatment strategies. Objectives: To verify the relationship between the development of AF and the mortality in patients over 80 years of age included in the sepsis protocol and to identify the risk factors that contribute to the development of AF in this population. Methods: Retrospective observational study, with a review of medical records and inclusion of 895 patients aged 80 years or older, included in the sepsis protocol of a high-complexity hospital in Sao Paulo/SP, from January 2018 to December 2020. Results: The incidence of AF in the sample was 13%. After multivariate analysis, using multiple logistic regression, it was possible to demonstrate an association of mortality, in the studied population, with the SOFA score OR 1.21(1.09-1.35), higher values of C reactive protein - OR 1.04 (1.01-1.06), need for vasoactive drugs - OR 2.4 (1.38-4.18), use of mechanical ventilation - OR 3.49 (1.82-6.71) and mainly AF - OR 3.7 (2.16-6.31). Conclusion: In the great elderly patient (80 years of age and older), septic, the development of AF was shown to be an independent risk factor for in-hospital mortality. 108625 Modality: E-Poster Young Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE The Clinical-Hemodynamic Profile and the Impact of Spirituality on the Quality of Life of Patients with Heart Failure Admitted to a Hospital in the Countryside of Sao Paulo State IEDA BARRETO MOURAO BERTINI1, Sofia Goncalves Tonoli1, Reinaldo Jose Gianini1, Emerson de Albuquerque Seixas1 (1) Pontificia Universidade Catolica de Sao Paulo (PUCSP) Introduction: Heart Failure (HF) is a disease where the heart is unable to properly pump blood around the body to support the metabolic needs. HF is associated with frequent underlying symptoms and complex treatments, which compromises a quality of life. The suffering can be lessened with a holistic approach focused on spirituality, which has been shown to affect the health and wellbeing of people with chronic diseases. Objective: To assess the clinical-hemodynamical profile of patients with HF to test if spirituality correlates with quality of life. Methodology: A cross-sectional study was undertaken, where two questionnaires were applied: i) Minnesorta Living with HF Questionaire (MLHFQ), to address the quality of life of patients with HF and ii) Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12), regarding the spiritual wellbeing of chronic patients. The patient's classification according to the New York Heart Association (NYHA) and the Stevenson hemodynamic profile were also used. Statistical tests were performed using STATA(r), through Pearson's correlation and linear regression. A total of 41 individuals >=18 years old with HF were interviewed. Results: Most respondents were male (53%) and the mean age of respondents was 66 years old. The mean HF etiologies identified were hypertense (37%), ischemic (34%) and valvular (12%), with the majority of patients falling into NYHA class III (41%) and Stevenson category B (90%). According to the FACIT-Sp-12 classification suggested by the authors of this study, as there are no other classifications in the literature, 2.4% showed low levels of spirituality and 65.8% showed high levels. According to the MLHFQ, 24.4% of respondents have great quality of life and 22% have a bad one. When both questionaires were correlated, there was a significant r coefficient of -0.45, showing a significant inversely proportional relationship (p-value 0.003), meaning higher the levels of spirituality are associated with lessend symptoms in patients with HF. However, when FACIT-Sp-1 was correlated with both the NYHA and the Stevenson classification, no stastistically significant relationships were found. Conclusion: A holistic approach focused on spirituality in patients with HF could have a positive effects on their quality of life through lessened symptoms. However, there is no evidence to suggest that spirituality has an effect on either the functional status or hemodynamic profile of patients. 108163 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE The Role of Liraglutide on Cardiac Function in an Experimental Model of Acute Doxorubicin-Induced Cardiotoxicity CAROLINA RODRIGUES TONON1, Paola da Silva Balin1, Marina Gaiato Monte1, Danilo Malmonge Barbosa Luciano1, Natalia Fernanda Ferreira1, Marcos Ferreira Minicucci1, Paula Schimdt Azevedo1, Sergio Alberto Rupp de Paiva1, Leonardo Antonio Mamede Zornoff1, Marina Politi Okoshi1, Katashi Okoshi1, Bertha Furlan Polegato1 (1) Faculdade de Medicina de Botucatu Background: Cancer is one of the main causes of morbidity and mortality worldwide. Despite doxorubicin (DOX) being an effective chemotherapy drug, DOX-induced cardiotoxicity is the most severe side effect, limiting treatment and worsening quality of life. There is no effective treatment for preventing DOX-induced cardiotoxicity. Glucagon like peptide-1 (GLP-1) analogs such as liraglutide reduce oxidative stress and inflammation. Purpose: To evaluate the role of liraglutide in acute DOX-induced cardiotoxicity in rats. Methods: 62 male Wistar rats were allocated into 4 groups: Control (C), DOX (D), Liraglutide (L), and DOX + Liraglutide (DL). The animals in L and DL groups received a subcutaneous injection of 0.6 mg/kg liraglutide daily while C and D groups received a subcutaneous injection of an equivalent volume of saline daily, for 2 weeks. After 12 days, D and DL groups received an intraperitoneal injection of DOX (20 mg/kg). Rats were submitted to echocardiogram and isolated heart study 48 hours after DOX injection. Statistical analysis: one-way ANOVA. Results: In the first 12 days, L and DL had lower food ingestion and body weight than C and D. After DOX treatment, body weight was lower in D and DL than C and L and lower in DL than D. In isolated heart study, DOX decreased +dP/dt (C 4518 +- 1469; D 2083 +- 534; L 4125 +- 647; DL 2150 +- 399 mmHg/s; p < 0.001) and -dP/dt (C 2679 +- 886; D 1292 +- 504; L 2896 +- 496; DL 1413 +- 285 mmHg/s; p < 0.001), with no changes between DL and D. In echocardiogram, D and DL exhibited lower peak systolic annular velocity at tissue Doppler [C 3.7 (3.2-4.2); D 3.1 (3.0-3.5); L 3.8 (3.4-4.0); DL 2.9 (2.7-3.0) cm/s, p < 0.001], and posterior wall shortening velocity (C 39 +- 4.5; D 32 +- 2.5; L 41 +- 5.0; DL 30 +- 2.9 mm/s; p < 0.001) than C and L. Liraglutide did not change these variables. D and DL had decreased E waves (C 77.2 +- 10.5; D 56.6 +- 9.0; L 74.3 +- 7.4; DL 52.5 +- 9.6 cm/s; p < 0.001) and A (C 56.9 +- 13.8; D 46.7 +- 10.4; L 56.3 +- 16.6; DL 39.8 +- 10.3 cm/s; p = 0.002) than C and L. DL showed increased isovolumetric relaxation time normalized to heart rate (C 54 +- 4.9; D 58 +- 8.0; L 51 +- 6.1; DL 65 +- 8.8; p < 0.001) than C, L, and D. Conclusion: Liraglutide administration does not attenuate doxorubicin-induced acute cardiac dysfunction. 108578 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Percutaneous Mitral Commissurotomy for Mitral Stenosis Patients: A 20 Years Follow-Up RICARDO JORGE DOS REIS ALVES PINTO1, Miguel Martins Carvalho1, Tania Proenca1, Catarina Costa1, Ana Filipa Amador1, Joao Calvao1, Catarina Marques1, Andre Cabrita1, Luis Santos1, Mariana Paiva1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao, Porto, Portugal Percutaneous mitral commissurotomy (PMC) is a viable alternative to mitral valve (MV) surgery in the treatment of clinically significant mitral stenosis (MS). Our aim was to evaluate the long-term results of PMC in patients (pts) with rheumatic MS and to compare events concerning pulmonary hypertension (PH) presence. We analysed all pts between 1991 and 2008 with rheumatic MS undergoing PMC. MACE was a composite of all-cause mortality, MV re-intervention or cardiovascular hospitalization. A total of 124 pts were enrolled: 87% were female, mean age of 46 +- 11 years (yrs) and mean follow-up (FUP) of 20 +- 6 yrs. Before PMC, 34% were in NYHA class >= III, 81% had Wilkins score <=8, all had preserved biventricular function, 83% presented PH; mean transvalvular gradient (TVG) and mitral valve area (MVA) were 12.8 mmHg and 1.0 cm2. Most of the procedures were successful (91%) and without major complications (94%), with mean MVA improvement of 0.9 cm2 and reduction of 8.5 mmHg in TVG and 9.7 mmHg in PASP after PMC. During long-term FUP, 42% of pts were re-interventioned and 24% died. In pts non-submitted to re-intervention, TVG and PASP remained similar throughout FUP, while MVA reduced over time, yet still statistically superior to baseline MVA (1.6 vs 1.0 cm2, p < 0.001). In time-to-event analysis, approximately 80% of pts kept uneventful after 10 yrs; after 30 yrs, >20% continued MACE-free and 50% alive. Regarding PH before PMC, there was no significant difference in MACE or mortality (p = 0,846 and p = 0.661, respectively). After long-term FUP, pts maintained reduction in TVG and PASP and a smaller but significative improvement in MVA. Most pts were MACE-free after 10 yrs and half were alive after 30 yrs. There was no difference in all-cause mortality or MACE concerning PH presence. 108271 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Validation of a New Method for Monitoring the Electrocardiographic Signal and Diagnosis of Heart Arrhythmia ERIC SANTOS RODRIGUES DE OLIVEIRA1, Larissa Araujo de Lucena1, Vitor Martinez Silva1, Antonio Lucas Arruda de Oliveira1, William Santos Rodrigues de Oliveira1, Nestor Rodrigues de Oliveira Neto1 (1) Hospital Universitario Onofre Lopes (HUOL) - Universidade Federal do Rio Grande do Norte (UFRN) Introduction: Rhythm disorders often present intermittently, making it difficult to record them. However, the electrocardiogram (ECG) performed during the event allows diagnosing the type of arrhythmia. Several studies have shown that portable devices can diagnose rhythm disorders, making these devices a practical alternative to the expensive and poorly available equipment. Thus, we hypothesize that our low complexity and cost device can monitor cardiac rhythm and diagnose cardiac arrhythmias with a single-lead ECG. Objectives: To evaluate a low-cost system's accuracy and technical quality for recording ECG and diagnosing cardiac arrhythmias. Methods: This is a validation study where outpatient or hospitalized patients are selected based on continuous cardiac monitoring and standard 12-lead ECG. Patients who had cardiac arrhythmia underwent a 12-lead ECG, and then the heart rhythm was recorded with a lead similar to CM5 through the new device. The device comprises a biological signal amplifier associated with filters connected to the smartphone. We will categorize the records into six rhythm groups, which will give us its diagnosis accuracy by comparing the device and the 12 lead ECG registers. Results: Presently, there are 30 records made with the device. Of these, 29 were of satisfactory quality. 1 was excluded for artifact influence. The general profile of the patients from the study was the median age of 55; 15 were men, 13 women, 1 undetermined; 12 had no comorbidities, 1 case of hypertrophic cardiomyopathy, 4 congestive heart failure, 4 hypertension, 3 diabetes mellitus. The rhythm profile of the registers is 15 with sinus rhythm, 7 bradycardia, 5 atrial fibrillation, 1 supraventricular or ventricular ectopy, 1 narrow qrs tachycardia, no wide qrs tachycardia so far. The device diagnosis accuracy is undetermined as we have not compared the device registers and the 12-lead ECG yet. Conclusions: The partial results show a low-cost mobile device that records in satisfactory quality and can be a tool for diagnosing rhythm disorders. According to the initial analysis of 30 tracings, the quality was satisfactory in 96.67% of the cases. Our solution is an efficient lower price alternative to other existing devices. The main limitation of this study is the result's initial state, which makes it challenging to verify the performance of the tested device. Thus we only accessed its ability to perform tracings of good quality. 108355 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Coronary Intervention in Late Presentation Acute Myocardial Infarction Without Viability. Effects on Left Ventricular Remodelling and Contractility - Rationale and Design BARBARA PORTO VALENTE1, Jose de Ribamar Costa Junior1, Ibraim Masciarelli F Pinto1, Bruno Pereira Albuquerque Coelho1, Gabriela Carolina Santamaria Naranjo1, Luciano de Figueiredo Aguiar Filho1, Paul Salvador1, Tiago Senra1, Vivian Lerner Amato1, Jose Roberto Tuma da Ponte Junior1, Ricardo Pavanello1, Pedro Silvio Farsky1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: The potential benefits attributable to late reperfusion fall under the "open artery hypothesis", in which the stunned peri-infarction zone after revascularization restores blood supply, improving its contractility. A study showed that late coronary recanalization after myocardial infarction (MI), irrespective of the viability status, improved left ventricular ejection fraction (LVEF) and myocardial contractility mainly in the segments adjacent and distant to the infarction. Purpose: To evaluate whether late recanalization in patients with STEMI without viability by Cardiovascular Magnetic Resonance (CMR) can reduce the reverse remodeling. Viable cases will be kept in the registry. Methods: This is a prospective randomized controlled trial, with at least 6 months follow-up. Patients with STEMI not reperfused between 24 hours and 28 days with IRA with lesion greater than 50% with segmental dysfunction and absence of viability on CMR are eligible for inclusion. Patients with previous MI, cardiomyopathy or clinical instability are excluded. Participants randomly assigned (1:1) to PCI and Optimal Medical Treatment (OMT) or only OMT. Expected outcome is the change on reverse remodeling of the end systolic volume at 6 months likewise the improvement in segmental contractility at 6 months. The sample size of 35 patients in each group provides 80% power with a two-sided significance level of 0.05. Descriptive statistics and statistical inferential methods are employed to measure changes between the groups. The trial has local ethical review board approval. Results: 28 patients have been already enrolled. Conclusion: This trial will provide insights into the potential benefits of opening the IRA in segments without viability, improving contractility of surrounding myocardium. 108396 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Effects of Sodium Glucose Co-Transporter 2 Inhibition on Muscle Energy Metabolism in Infarcted Rats LIDIANE MOREIRA SOUZA1, Bruna Brasil Brandao2, Luana Urbano Pagan1, Mariana Gatto1, Felipe Cesar Damatto1, Eder Anderson Rodrigues1, Patricia Aparecida Borim1, Gilson Masahiro Murata3, Leonardo Antonio Mamede Zornoff1, Katashi Okoshi1, Marina Politi Okoshi1 (1) Botucatu Medical School, Sao Paulo State University, UNESP; (2) Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; (3) Institute of Biomedical Science, Sao Paulo University, USP Introduction: Skeletal muscle energy metabolism is commonly altered in heart failure patients, with a metabolic shift from oxidative to glycolytic muscle fiber. These changes contribute to reduced functional capacity. Sodium glucose co-transporter type 2 (SGLT2) inhibitors improve cardiovascular outcomes in both diabetic and non-diabetic patients, as well as those with and without heart failure. However, the effects of SGLT2 inhibitors on skeletal muscle during heart failure have not been established. The aim of this study was to assess the metabolic effect of empagliflozin (EMPA) on skeletal muscle of rats with myocardial infarction (MI)-induced heart failure. Methods: One week after MI induction or simulated surgery, male Wistar rats were divided into four groups: Sham (n = 10), Sham+Empa (n = 12), MI (n = 10), and MI+Empa (n = 09). EMPA was added to rat chow (5 mg/kg/day). Rats were supplied with ad libitum water and chow for 12 weeks. Infarct size was measured by histological analysis. Metabolic enzyme activity in the soleus muscle was assessed by spectrophotometry. Statistical analysis: ANOVA and Tukey, and Student's t tests. Results: Only rats with infarction size greater than 35% of total left ventricle area were included in this study. Infarction size did not differ between infarcted groups (MI 41.8 +- 4.2; MI+Empa 40.7 +- 5.7 of total left ventricle area). In the MI soleus muscle, metabolic enzyme activity of glucose-6-phosphate-dehydrogenase, citrate synthase and beta-hydroxy-acyl-dehydrogenase was higher than the Sham group. These changes were not observed in the MI+Empa group. MI+Empa had lower hexokinase, phosfructokinase, and pyruvate kinase activity (glycolytic metabolism enzymes), and lower citrate synthase and glucose-6-phosphate-dehydrogenase activity than MI. Conclusion: Chronic treatment with SGLT2 inhibitor empagliflozin prevents metabolic abnormalities in skeletal muscle in infarcted rats. 108368 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Very Long-Term Mortality After ST Elevation Myocardial Infarction (Stemi) Complicated by Cardiogenic Shock GABRIEL KANHOUCHE1, Jose Nicolau1, Talia Falcao Dalcoquio1, Mauricio Felippi de Sa Marchi1, Roberto R Giraldez1, Remo Furtado1, Luciano Baracioli1, Roberto Kalil Filho1, Fabio Sandoli de Brito Junior1, Alexandre Abizaid1, Henrique Barbosa Ribeiro1 (1) Heart Institute of Sao Paulo - InCor/HCFMUSP Introduction: About 5-10% of myocardial infarctions develop severe form of presentation, with cardiogenic shock (CS). Despite evidence showing higher in-hospital and short-term mortality in patients with STEMI complicated by CS, long-term follow-up data is lacking. Hypothesis: The aim of this study was to assess very long-term prognosis of survived patients with STEMI complicated by CS. Methods: STEMI patients (n = 1,444) were included (1998-2017) and followed for up to 17.6 years (median 5.4 [2.5-9.9] years). Long-term survival was assessed by Log-Rank test. Results: Compared to STEMI without CS, patients who presented CS (n = 118) had no significant differences regarding age (62.0 +- 11.8 vs. 60.7 +- 12.7; p = 0.31) and female sex (28.0% vs. 25.1%, p = 0.51), but had lower left ventricle ejection fraction (38.8 +- 13.0% vs. 49.7 +- 13.1%, p < 0.001) and higher mean baseline creatinine levels (1.4 +- 0.6 mg/dL vs. 1.2 +- 0.7 mg/dL, p = 0.002). Of note, CS patients presented higher in-hospital mortality (42.2%) compared to those without CS (OR = 28.5; 18.1-44.7, p < 0.001). Long-term survival was lower in patients with CS (10.7 +- 0.6 vs. 13.3 +- 0.2 years, log rank = 0.016). By multivariate analysis adjusted for baseline characteristics the main factors predicting mortality were age (HR = 1.06; CI95% 1.05-1.07, p < 0.001), previous MI (HR = 1.34;CI% 1.06-1.69, p = 0.01), history of heart failure (HR = 1.65; CI95% 1.15-2.37, p = 0.007), stroke (HR = 1.67; CI95% 1.12-2.47, p = 0.01), diabetes (HR = 1.41; CI95% 1.14-1.74, p = 0.001) and the presence of CS (HR = 3.65; CI95% 2.92-4.56, p < 0.001). Conclusion: In a very long-term follow-up after a STEMI, CS increased ~4-fold the mortality rates. After hospital discharge, CS remains an important independent risk factor for death in the follow-up. Our findings reinforce the importance of intensive clinical monitoring with optimal medical and non-pharmacological therapy for the remarkable risk factors in the very long-term post-STEMI complicated by CS. 108369 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Viability Assessment as a Strategy to Reduce Long Term Events in Left Anterior Descendent Artery with Chronic Total Occlusion BARBARA PORTO VALENTE1, Maria Julia Silveira Souto1, Manuela Gomes de Aguiar1, Gabriela Carolina Santamaria Naranjo1, Ismar Junior Peinado Lijeron1, Rodrigo Urdan1, Lucas Ferreira Marcondes Lemos1, Cesar Henrique Morais Alves1, Kelvin Henrique Vilalva1, Maria Isabel Del Monaco1, Luciana Uint1, Ricardo Pavanello1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Late intervention of a chronic total occlusion (CTO) in stable patients is not routinely recommended by randomized trials. Previous studies have confirmed the negative effect of CTOs on prognosis. Purpose: To evaluate if a strategy of viability assessment (VA) to guide revascularization in the left anterior descendent artery (LAD) CTO can reduce 5-year clinical outcomes. Methods: Retrospective cohort with at 5-year follow-up of 223 patients with LAD with CTO without any other significant lesion. Patients with previous myocardial infarction, cardiomyopathy or clinical instability were excluded. The primary outcome was the composite end point of myocardial infarction (MI), death, new LAD revascularization, heart failure hospitalization (HFH) and severe arrhythmias. Results: We identified 223 patients with LAD CTO as a single lesion. Only 53 (23.7%) had VA to guide therapy compared to 170 (76.2%) with no VA (NVA). The mean ejection fraction was higher in the group with NVA (54.5 +/- 13.1 vs 41.5 +/- 11.8 with p < 0.001). The occurrence of angina was more common in the NVA group (64.7% vs 30.2% with p < 0.001), mainly due to Canadian Cardiology Society II (71.8%). The VA group was more frequently maintained in optimal medical therapy (OMT) (54.7%) compared to the NVA group (23.5%). NVA group underwent revascularization more often than the VA group, PCI was performed in 59.4% vs 41.5% and CABG in 17.1% vs 3.8% respectively. The primary outcome occurred in 5.7% in the VA group compared to 22.4% in the NVA (p = 0.056). Conclusion: VA is a feasible strategy to reduce the need of unnecessary interventions. There was a marginal reduction of the total number of events in the VA group in the 5-year follow-up, mainly with respect to reducing the need for new LAD revascularization. 108397 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Prognostic Value of Autonomic Nervous System Imbalance in Heart Failure Patients with Low Left Ventricular Ejection Fraction Receiving Cardiac Contractility Modulation ALLA PAVLOVSKAYA2, Elena Lyasnikova1, Ekaterina Zhabina1, Maria Trukshina1, Victoria Galenko1, Larisa Prokopova1, Tatiana Lelyavina1, Marianna Wander1, Evgeniy Mikhaylov1, Maria Sitnikova1 (1) Almazov National Medical Research Centre; (2) Semashko Republican Clinical Hospital Introduction: Experimental data have showed the effect of cardiac contractility modulation (CCM) on the autonomic nervous system (ANS) activity. However, there are limited data regarding the prognostic value of ANS and its imbalance assessed by heart rate variability (HRV) in patients receiving CCM. Objective. To evaluate association of HRV with prognosis in heart failure patients with HFrEF and sinus rhythm undergoing CCM therapy. Methods: This retrospective study included 52 patients with HFrEF, II/III fc, being on optimal drug therapy more than 3 months (age 53 +- 10.4 years, 86% men, CAD 73%, CABG/PCI 54%, ICD 21%, sinus rhythm 100%, LVEF 25 +- 6%, peakVO2 16.8 +- 4.8 ml/min/kg, NtproBNP 1087.5 [706.6;1752.7] pg/mL), who underwent CCM device implantation with further followed by a team of heart failure specialists. HRV parameters were calculated using 24-hour ECG monitoring before device implantation. The relationship between pre-implant time-domain (SDNN) and frequency-domain (LF, HF, LF/HF ratio from 24-hour; VLF from a 5-min segment of the resting period) and the endpoint of 3-year all-cause death was analyzed. Results: During a mean 36 +- 2 months of follow-up, 11 patients reached the endpoint. All patients were divided into 2 groups depending of the SDNN duration. Initially, SDNN <100 ms was observed in 18 patients (34.6%). The Kaplan-Meier analysis using the log-rank test showed worse prognosis among patients with low SDNN (p = 0.01). LF, HF, VLF during 5-min were significantly higher in the subgroup of surviving patients (p = 0.02, p = 0.04 and p = 0.001, respectively) and low VLF (<=179 ms2) was associated with an increased risk of HF-death (p = 0,005). Conclusions: Our preliminary findings indicate that baseline ANS dysfunction (quantified by low HRV indices) in patients with HFrEF receiving CCM-therapy was associated with the all-cause mortality and cardiac events within 3 years. The future of risk stratification of events in HF patients undergoing CCM lies in the integration of HRV data with other prognostic factors, imaging methods and laboratory biomarkers. It might help in optimizing qualifications for this treatment. 108387 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Hospitalizations for Acute Myocardial Infarction in Brazil from 2010 to 2019 HILDEMAN DIAS DA COSTA1, Hildeman Dias da Costa1, Luiz Felipe Facanha Ramos2, Leo Christyan Alves de Lima3, Matheus Akira Suzuki de Oliveira1, Mateus Viana Osorio de Barros1, Matheus Rodrigues Gomes3, Mathews Barbosa Santiago4, Milena Stephanie Alves Matos3, Julia de Avila Gutierrez5, Laura Jane Franca Lacerda3, Maria Beatriz Mourao8 (1) Universidade Federal de Rondonia; (2) Universidade Federal do Amapa; (3) Centro Universitario Sao Lucas; (4) Centro Universitario Uninorte; (5) Faculdades Integradas Aparicio Carvalho Introduction: Myocardial infarction, or heart attack, is the death of cells in a region of the heart muscle due to the formation of a clot that interrupts blood flow in a sudden and intense way. Fast and efficient care proves to be of fundamental importance to reduce patient morbidity and mortality. Objective: To analyze the epidemiological profile of hospitalizations for acute myocardial infarction on an emergency basis in Brazil between 2010 and 2019. Methods: This is a cross-sectional epidemiological study, in which data were obtained from the Department of SUS Informatics - DATASUS. The variables researched were: total hospitalizations, sex, color/race, age group, deaths and mortality rate. The research period was delimited between the years 2010 and 2019. Results: 911,607 hospitalizations were recorded. Males reported 578,246 hospitalizations, and females 333,361. The white color/race recorded 372,948 hospitalizations. The most affected age group was 60 to 69 years old, with 266,378 hospitalizations. The total number of deaths was 109,295. The mean mortality rate was 11.99. Mortality rates in 2010 and 2019 were 13.46 and 10.37, respectively. Conclusions: The epidemiological profile of hospitalizations was characterized by male, white individuals aged between 60 and 69 years. Although the number of hospitalizations and deaths have increased, mortality rates from AMI have been decreasing over the years. 108400 Modality: E-Poster Young Researcher - Non-case Report Category: PSYCHOLOGY Behavioral Cardiology: Smoking in Hospitalized Brazilian Heart Disease Patients LEONARDO SANTOS DE SOUZA1, Leonardo Santos de Souza1, Silvia Maria Cury Ismael1 (1) Hospital do Coracao de Sao Paulo Background: Considering the complex public health challenge of preventing tobacco-associated diseases as the main cause of morbidity and mortality, understanding the risky health behavior variables thus enabling their proper management. Few Brazilian studies have investigated this issue in the in-hospital setting and in supplementary health frameworks. Objectives: To characterize and assess the variables involved in the smoking behavior of in-patients with heart disease. Methods: Exploratory cross-sectional study approved by the Research Ethics Committee (CAAE no44662921.0.0000.0060) that assessed 211 tobacco-addict patients with heart disease of which 77.7% were men, with a mean age of 60.5 years (+-11.4), evaluated in the last five years by the psychology service of a private hospital in the city of Sao Paulo. Data collected retrospectively through the Smoker Profile Questionnaire, the Fagerstrom test, the Stages of Behavior Change and Reasons for Smoking Scale were submitted to descriptive analyses as well as non-parametric tests, Chi-Square and Fisher's Exact tests, using the R Core Team software (2021) and setting a p-value <0.05 as statistically significant. Results: There was a prevalence (p = <0.001) of married men (72%) professionally active (82.3%) with higher education (75%). Consumption had been 20 cigarettes a day for 39.4 years (+-13.4) with ineffective cessation attempts (M = 1.9 +- 1.8). Smoking was adhered to for pleasure (85.8%), stress reduction (81.5%) and physical dependence (62.1%), despite motivation to quit (82.9%). In addition, the respondents reported difficulty not smoking when they were sad (46.2%), angry (49.8%) or anxious (60.8%). There was an association (p < 0.001) between time of active smoking, age, hypertension and coronary artery disease, as well as cronic obstructive pulmonary disease (p < 0.001), overweight (p = 0.027), acute myocardial infarction (p = 0.022). Nicotine dependence was associated with chronic alcoholism (p = 0.012) and longer hospital stay (p = 0.032). Weight control (p = 0.003) and stress reduction (p = 0.018) were the main reasons for women with heart disease to keep smoking. Conclusion: Smoking in patients with heart disease has multiple functions and respondent-operant interactions, which makes smoking more resistant to change and demands a thorough functional analysis and comprehensive interventions still during hospitalization, for an efficient secondary prevention. 112369 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence of Cardiovascular Diseases at the Center of Medical Specialties of Cesupa (Cemec), from January to December 2013 GIOVANNA BOLINI BRAZAO1, ISABELLA ROCHA GONCALVES1, RAISSA MARIA CHAVES LOBATO1 (1) Centro Universitario do Estado do Para (CESUPA) Introduction: Cardiovascular diseases (CVDs) affects the heart and blood vessels, with the ability to compromise other vital systems, representing important causes of deaths worldwide. In Brazil, they are a major public health problem, being associated with several risk factors. To change this situation, it is necessary to know about the epidemiological profile of CVDs at regional level, in order to assist prevention and intervention in modifiable risk factors, through public policies and health actions. Objectives: To verify the prevalence of cardiovascular diseases in the Center for Medical Specialties of Cesupa - CEMEC outpatient clinics; to identify risk factors in the clinical history and their correlation with the development of CVDs; to identify the epidemiological profile of patients affected by CVDs. Methods: The prevalence of CVDs at CEMEC, in the metropolitan region of Belem-PA, during 2013, was evaluated through an observational and cross-sectional study, carried out from the analysis of medical records of the cardiology outpatient clinic in the referred period. Results: The study analyzed the medical records of 152 patients; 40.8% of these were male and the other 59.2%, female. In terms of the neighborhood of origin of these patients, Marambaia (16.4%) and Mangueirao (6.5%) stood out with the largest number of residents who are users of CEMEC's cardiology outpatient clinic. The history of previous illness, medications in use, life habits, signs and symptoms at the time of consultation and other variables of each patient were analyzed, in order to record, create statistics and understand the needs of the outpatient clinic. Conclusion: Certainly, the poor filling of the medical records collected and the great demand for cardiac care in CEMEC draws attention. In addition, the close correlation between CVDs recorded with the risk factors prevalent in the study population suggests an important criterion in which future local policies can be developed. 108424 Modality: E-Poster Young Researcher - Non-case Report Category: DYSLIPIDEMIA Algorithm for Familial Hypercholesterolemia Detection and Screening in Lithuanian Population URTE ALIOSAITIENE1, Zaneta Petrulioniene1, Egle Skiauteryte2, Dovile Gabartaite1, Emilija Meskene1, Juste Staigyte1, Viktoras Sutkus2, Rimante Cerkauskiene1 (1) Vilnius university faculty of medicine; (2) Vilnius university hospital Santaros Klinikos Background and aims: Familial hypercholesterolemia (FH) is highly underdiagnosed and undertreated congenital disorder worldwide. In this study we aim to establish an algorithm for most efficient FH detection and screening in Lithuanian population. Methods: Since 2016 more than 220 FH patients have been included in Lithuanian FH registry, which is based on Lithuanian High Cardiovascular Risk (LitHiR) primary prevention programme and established as a part of The European Atherosclerosis Society (EAS) Familial Hypercholesterolaemia Studies Collaboration (FHSC) global FH registry. Adults with clinically suspected FH (LDL-C >=5 mmol/L) were referred to specialist lipid centre, where detailed personal and familial anamnesis, physical examination, evaluation of laboratory and instrumental tests have been performed and secondary causes of dyslipidemia have been excluded. The clinical diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria were determined. Patients with DLCN score >=6 and/or LDL-C >=6,5 mmol/L were referred to genetic testing. Cascade first-degree relatives screening were initiated if an index-case meets DLCN criteria for definite or probable FH. Results: During the period of 2016-2021 data of 220 patients (120 females, 100 males) were included in the analysis. Mean age at FH diagnosis were 45,3 (+-12,6) years with significant difference between genders: 48,17 (+-12,68) years in women and 41,73 (+-11,5) in men (p < 0,001). According to DLCN criteria definite FH has been diagnosed for 56 subjects (25,5%), probable FH - 65 patients (29,5%), possible FH - 68 subjects (30,9%) and 31 patients (14,1%) has been included in unlikely FH group. Results of genetic testing have been received for 126 patients: no mutation or variant of unknown significance (VUS) had been detected in 83 patients (65,87%), LDL receptor mutation has been found in 24 patients (19,05%) and ApoB receptor mutation - in 19 subjects (15,08%). Conclusions: The algorithm we use for FH detection seems to be valuable tool for recognizing patients who are in the highest probability of having FH gene mutation. High percent of undetected mutations may be associated with a number of genetically tested patients who were included in possible and unlikely FH groups. Therefore, it could be assumed that in the first instance patients who meet criteria for probable and definite FH should be referred for genetic testing and initiation of cascade screening should be started at this point. 108432 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Atherosclerosis, Deep Vein Thrombosis and Chronic Venous Insufficiency: Is There a Link? a Case - Control Study JOSE PESENTI1, Leticia Gonzalez2, Francisco Vargas4, Gonzalo Martinez5, Prakash Saha6, Marcelo E. Andia2 (1) School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile; (2) ANID-Millennium Institute for Intelligent Healthcare Engineering, Santiago, Chile; (3) Biomedical Imaging Center, School of Medicine, Pontificia Universidad Catolica, Santiago, Chile; (4) Vascular Surgery Department, School of Medicine, Pontificia Universidad Catolica, Santiago, Chile; (5) Cardiovascular Division, School of Medicine, Pontificia Universidad Catolica, Santiago, Chile; (6) School of Cardiovascular Medicine & Sciences, King's College London, London, UK Introduction: Atherosclerosis, deep vein thrombosis (DVT) and chronic venous insufficiency (CVI) have been seen as different entities, however thrombo-inflammation could be the link between them. In this study we explore this relationship in patients with DVT, CVI and controls. Methods: We recruited 7 patients with DVT and 9 with CVI from the Vascular Surgery Department of our University Hospital and 9 healthy controls matched for gender and age. We registered their cardiovascular risk factors and obtained blood tests for hs-CRP, Circulating Endothelial Cells (CEC), ICAM-1 and CXCL7 as biomarkers of inflammation, endothelial and platelets activation. Carotids plaques were classified according to the AHA MRI classification. We used Principal Component Analysis (PCA) and Hierarchical Clustering Analysis (HCA) to study the combined effect of all variables. Results: There were no significant differences between the groups for inflammatory markers and cardiovascular risk factors (Fig.A). However, using PCA and HCA we identified 2 clusters: cluster 1 with all the controls, one DVT and three CVI patients; and cluster 2 with only DVT and CVI subjects (Fig.B). There was a significant difference between carotid plaque complexity between both clusters (Fig.C). Conclusions: Our study supports the link between inflammation, DVT and atherosclerosis, and contributes to consider CVI as another risk factor for atherosclerosis. Acknowledgment: FONDECYT 1180525. 108463 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Educational and Drug Interventions for Blood Pressure Control in Kidney Transplant Recipients Based on Ambulatory Blood Pressure Monitoring RAFAEL NAUFEL DE SA REBELO1, Rafael Naufel de Sa Rebelo1, Cibele Isaac Saad Rodrigues1 (1) Pontificia Universidade Catolica de Sao Paulo The goal of this study was to compare blood pressure (BP) control, pre-and post-educational and therapeutical interventions in kidney transplant recipients (KTR) obtained by office (OBP) and ambulatory blood pressure monitoring (ABPM) at baseline and 6 months later. It is an observational, and interventional cohort study with 33 adult hypertensive and non-diabetic KTR. Data collection included three medical appointments bimonthly. Statistical analysis included a paired t-test, Student's t-test, and Fisher's test. We observed that OBP presents mean values higher than those obtained by the ABPM (p < 0.05) and high prevalence of atypical BP curve, especially white coat hypertension (46.1%), and 90% showed abnormal nocturnal dipping. Association of drug adjustments plus lifestyle changes was the most needed intervention (88%). The diastolic OBP significantly decreased after 6 months (p = 0.040). Patients were more likely to follow the diet changing (69,3%) than the physical activity program (34.6%). Dietary modification was associated with a significant reduction of ABPM mean systolic BP. This study showed high prevalence of hypertension, detected different phenotypes using ABPM, and implemented personalized actions to achieved BP control. These changes proved to be effective after a 6-moths showing that ABPM is an important strategy for BP diagnosis and follow-up in KTR. 112340 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOGERIATRICS Heart Disease in People Older than 95 Years - the Cardiogeriatric Clinic Experience in Mexico MARIANA GAMBOA ESPARZA1, Ana Mercedes Andrade Aguilar2, Arturo Moreno Perez1, Natalia Capistran Paramo1, Henry De Las Salas Perez1, Carlos Alberto Guillen Rosaldo1, Luis Alberto Lasses y Ojeda1 (1) Instituto Nacional de Cardiologia Ignacio Chavez INCICH; (2) Hospital General Regional No. 46 IMSS Introduction: Very old patients form an increasing population in cardiology consultation, then specialized geriatric care is needed. Objective: To describe cardiovascular and geriatric profile in patients older than 95 years with heart disease. Methods: We performed a cross-sectional study collecting data through clinical record and a telephone survey to complete a geriatric comprehensive assessment (GCA) and cardiovascular variables of patients older than 95 years attending a tertiary referral hospital during 2021. Results: Of a total 74 patients older than 95 years, 36 participated in this study. 19 were deceased and 19 were unreachable. Mean age is 97 +- 1.79 years, and 75% were female. Mean years attending Cardiogeriatric Clinic is 6.2 +- 3.46. The most common diagnosis was hypertension (75%) followed by arrythmia (61%). Atrial fibrillation was the most common arrythmia (40%). 36% of patients have pacemaker. Ten patients are anticoagulated and in reduced dose. Only 3 participants visited emergency room in the last year. None of them was for bleeding. Prefrailty is present in 42% and Frailty in 53% of patients. Sarcopenia screening was positive in 69%. 13.8% had 2 or more falls. All patients have caregivers, and the majority self-reported a good health status. Even thought, 33% have depression and 28% have dementia. Conclusions: Geriatricians trained in heart diseases may improve outcomes in this population. Implementation of a Cardiogeriatric Clinic in a tertiary referral hospital is preparing new physicians' generations to design interventions for patients older than 95 years, especially in frailty, sarcopenia and falls. 108471 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Heart Transplantation in Brazil: An Epidemiological Study of Surgeries in the Last Ten Years (2012-2021) HILDEMAN DIAS DA COSTA1, Hildeman Dias da Costa1, Luiz Felipe Facanha Ramos2, Leo Christyan Alves de Lima3, Matheus Akira Suzuki de Oliveira1, Mateus Viana Osorio de Barros1, Mathews Barbosa Santiago4, Julia de Avila Gutierrez5, Laura Jane Franca Lacerda3, Ayrison de Melo Sousa4, Erica Mayara Gama Pinheiro1 (1) Universidade Federal de Rondonia; (2) Universidade Federal do Amapa; (3) Centro Universitario Sao Lucas; (4) Centro Universitario Uninorte; (5) Faculdades Integradas Aparicio Carvalho Introduction: According to the Brazilian Association of Organ Transplantation, the heart is the third most transplanted organ in Brazil, behind only the kidney and liver. Structural problems in the Brazilian health sector and the resistance of families to authorize donations are some of the main obstacles to performing surgeries. Objective: To analyze the epidemiological profile of heart transplant surgeries in Brazil in the last 10 years. Methods: This is a cross-sectional epidemiological study. Data were obtained from the Informatics Department of the Unified Health System - DATASUS. The variables studied were: total number of transplants, states that performed the most surgeries, average length of stay, deaths and mortality rate. The research period was delimited between 2012 and 2021. Results: 2,732 heart transplant surgeries were performed. In 2012 and 2021, 193 and 226 transplants were performed, respectively. Sao Paulo and Minas Gerais were the states that performed the most surgeries: 852 and 400, respectively. The average length of stay was 17.8 days. The total number of deaths was 311. The average mortality rate was 11.38. Conclusions: The epidemiological profile of transplants was characterized by surgeries that took place mainly in the states of Sao Paulo and Minas Gerais, with an average length of stay of hospitalizations of 18 days. The reduction in the number of surgeries in 2020 and 2021 may reflect the pandemic caused by COVID-19. 108481 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Trend of Mortality from Heart Failure in Brazil: 1998-2019 VILMEYZE LARISSA DE ARRUDA1, Vilmeyze Larissa de Arruda1, Lubia Maieles Gomes Machado1, Jaqueline Costa Lima1, Pamela Rodrigues de Souza Silva1 (1) Universidade Federal de Mato Grosso (UFMT) Introduction: Heart failure (HF) is characterized by decreased cardiac output and/or high filling pressures at rest or on exertion. HF is considered the most prevalent cardiovascular disease and the main cause of hospitalization in the Unified Health System. Objective: To analyze the trend of mortality from HF in Brazilians aged 50 years and over, within 21 years. Method: Ecological study with time series analysis of mortality from HF in Brazil, according to regions and federation units, in individuals aged 50 years and older in the period from 1998 to 2019. Deaths that had HF as the underlying cause (International classification of diseases -10: I50), that occurred during the study period were included in the study. Statistical analyzes were performed using the Stata 11.1 program. The HF mortality rate per 100,000 inhabitants was calculated. In the trend analysis, the Prais-Winsten regression was used. Results: Between 1998 and 2019, 567,789 deaths from HF were recorded in adults over 50 years of age, which corresponds to an average rate of 75.5 per 100,000 inhabitants. The trend was decreasing by sex, regions and in 23 FUs. The highest observed mortality rates occurred at older ages in all regions of the country. Conclusion: The trend of mortality rates from HF in adults aged 50 years and over among the federation units and Brazilian regions was decreasing over 21 years. There was an increasing trend in mortality from HF in the northern region and in the category other health facilities. 108598 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Association of Eight Genetic Polymorphisms to High Blood Pressure and Obesity in a Sample of Brazilian Adolescents. Rio De Janeiro Study II YASMIN LEMOS ROLLEMBERG CRUZ MACHADO2, Flavia Lopes Fonseca2, Rossana Ghessa Andrade de Freitas2, Pedro Pimenta de Mello Spineti2, Erika Maria Goncalves Campana2, Roberto Pozzan2, Maria Eliane Campos Magalhaes2, Dayse Aparecida da Silva1, Andrea Araujo Brandao2 (1) Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro (UERJ); (2) Faculty of Medical Sciences, State University of Rio de Janeiro (UERJ) Introduction: Several genetic polymorphisms have been investigated as potential risk predictors of cardiovascular (CV) diseases and their comorbidities mainly in adults from genetically homogenous populations; although their CV complications correlated with the presence of obesity and high blood pressure (BP) since childhood. Objective: To evaluate the association of eight SNPs in genes related to the renin-angiotensin-aldosterone system, endothelial function and leptin-melanocortin pathway with high blood pressure (BP) and obesity in a sample of admixed Brazilian adolescents from a longitudinal study. Methods: 1,054 Brazilian adolescents aged 10-15 years, both genders, were genotyped for rs699 (AGT), rs1799998 (CYP11B2), rs1799983 (NOS3), rs9939609 (FTO), rs1137101 (LEPR), rs3746619 and rs3827103 (MC3R), and rs17782313 (MC4R) through customized Multiplex Minisequencing System. Results: Prevalence of high BP and obesity were 13.5% and 41.4%, respectively. Minor A allele of rs3746619 (MC3R) was more prevalent in black (P = .001), in hypertensive (P = .017) and correlated with increased systolic BP (P = .023). G wild-type allele of rs1799983 (NOS3) was more prevalent in obese (BMI, P = .002; WC, P = .027), correlated with increased BMI (P = .020) and was associated with obesity in non-adjusted (OR = 0.713, P < .001) and adjusted regression models (OR = 0.730, P = .001). Variants rs3827103 (MC3R), rs699 (AGT) and rs1799998 (CYP11B2) presented different genotypic distributions according to color, gender, WC and BP status (P < .05). No other SNP was associated with elevated BP, obesity or their quantitative traits. Conclusion: The G wild-type allele of rs1799983 (NOS3) was associated with increased BMI and risk for obesity in admixed Brazilian adolescents with high BP. 108492 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY A Comparison of the 2021 Ckd-Epi Creatinine Equation and Cockcroft-Gault Formula in Patients Undergoing Cardiovascular Surgeries STELLA DE SOUZA VIEIRA1, Bianca Kajimoto Magalhaes1, Andressa Muzzo de Souza1, Marcelo Arruda Nakazone1, Lilia Nigro Maia1, Mauricio Nassau Machado3 (1) Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP; (2) Escola Paulista de Medicina - Universidade Federal de Sao Paulo - UNIFESP-EPM; (3) fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - FUNFARME Introduction: Although the use of the Cockcroft-Gault (CG) formula is no longer recommended, the ease of application still makes it widely used. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was updated to disregard the race statement, a non-biological construct. Objective: We evaluated the strength of agreement between the CG formula and the 2021 CKD-EPI equation and assessed the impact of disagreement between estimated glomerular filtration rates (eGFR) methods on outcomes. Methods: A total of 2,855 adult patients who underwent cardiac surgeries (isolated coronary artery bypass grafting or heart valve surgery) were analyzed. Linear regression, Bland-Altman plots and Cohen's Kappa statistics were used to determine the strength of agreement between the eGFR determinations. Cumulative survival curves were constructed to demonstrate the impact of renal function categories on mortality. Results: Sixty-one percent (1,748) and 23% (658) of the patients were classified by both equations as eGFR >=60 and <60 mL/min/1.73 m2, respectively. Sixteen percent of the patients were classified as discordant eGFR. There was a significant positive linear correlation (Spearman's rho, 0.817; P < 0.001) between the eGFR based on the CG formula compared with eGFR according to the 2021 CKD-EPI equation. The Bland-Altman plots showed that the mean difference between the methods was 2.5 with the 95% limits of agreement ranging from -30.8 to 35.8, but the one-sample T test of the difference showed disagreement between the eGFR methods (P < 0.001). Patients with prevalent eGFR 60 to <90 and 45 to <60 had modest strength of agreement (K = 0,389 and K = 0,365; respectively) and the percentage of agreement was 69.7% and 80.6%, respectively. There was only one agreement classified as good in the stage 5 (K = 0.729), but this group represented only 2.4% of our cohort. The Kaplan-Meier curves showed cumulative survival rates at 30-day of 95.8%, 91.5% and 83.9% for patients with eGFR >=60, discordant eGFRs, and eGFR <60 mL/min/1.73 m2 (P < 0.001). Conclusions: Despite of a positive linear correlation, the means of the differences between the two equations is statistically significant and the CG formula shows only modest strength of agreement with the 2021 CKD-EPI equation, limited to the prevalent strata of renal function. This finding suggests that the CG formula should be no longer used in cardiac surgery settings to estimate glomerular filtration rate. 108495 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Relationship between Sociodemographic Index and Cerebrovascular Disease in Brazil in the Period of 2000-2019 JOSE LUCAS PERES BICHARA1, Jose Lucas Peres Bichara1, Luiz Antonio Viegas de Miranda Bastos1, Paolo Blanco Villela1, Glaucia Moraes de Oliveira1 (1) Universidade Federal do Rio de Janeiro - UFRJ Introduction: Cardiovascular diseases (CVD) are the main causes of death in the world and in Brazil, and cerebrovascular diseases (CVD) are one of the main responsible for these statistics, a fact aggravated by the aging of the population. Previous studies have already suggested a relationship between the evolution of CVD mortality rates and socioeconomic indicators. Objective: To relate the evolution of CVD mortality rates and the sociodemographic index (SDI) from 2000 to 2019 in Brazil and in its federative units (FUs). Methods: Ecological time series study of deaths from CVD in Brazil. Crude and standardized mortality rate for CVD were analyzed by sex, age group and FU between 2000 and 2019. Data were correlated with the SDI. Deaths and population were taken from DATASUS to estimate crude and standardized mortality rates per 100,000 inhabitants (direct method with Brazilian population in 2000). The SDI for each UF was extracted from the Global Health Data Exchange website. Results: In the period, there were 1,925,765 deaths from CVD in Brazil, 50.54% of which were male. The national SDI ranged from 0.538 in 2000 to 0.64 in 2019, with constant growth in the period. At the same time, the age-standardized mortality rate for CVD decreased from 49.81/100,000 inhabitants to 30.98/100,000 inhabitants. In this way, CVD has become the second leading cause of mortality in the country. In the FUs, all states in the North and Northeast regions showed improveme. 108510 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of COVID-19 on Cardiac Surgeries in a Tertiary Care Center FERNANDA AREJANO VAUCHER1, Maria Antonia C. da Silva1, Maria Eduarda M. B. Busko1, Vanessa C. de Lima1, Thaisa R. F. Basagla1, Ana Karyn E. de Freitas1 (1) Irmandade Santa Casa de Misericordia de Curitiba (ISCMC) Background: The infection caused by COVID-19 in patients undergoing cardiac surgery leads to higher mortality and clinical complications in the postoperative period. In addition, most patients are older and have several comorbidities, which are factors of worse prognosis for disease progression. Objectives: This study aims to identify the impact of COVID-19 infection on the mortality of patients undergoing cardiac surgery within a 30-day period, as well as the incidence of clinical complications. Methods: We retrospectively evaluated 213 patients undergoing elective cardiac surgery or in the context of urgency and emergency, from January to December 2020, in a tertiary referral center. Of these, those who tested positive for COVID-19 within 30 days before or after the procedure were compared with those who did not have the infection in the period, considered the control group. Results: Of the 213 patients included in the study, 27 (12.6%) were diagnosed with COVID and 186 (87.3%) did not have the disease. Of the total, 95 were women (45%) and 118 were men (55%). The mean age was 62 years. There was no significant difference between the groups regarding epidemiological data. Mortality was significantly higher in the COVID-19 group (33% vs 15% patients in the control group). Complications such as arrhythmias (37% x 19%), prolonged ICU time (8 +- 8 days x 7 +- 7 days), total hospital stay (25 +- 16 days x 16 +- 19 days), respiratory failure requiring orotracheal intubation (30% x 1.1%), mechanical ventilation time (3.23 +- 7 days x 1.83 +- 5.48 days) and venous thrombosis (11% x 1.6%) were also more prevalent in the COVID group -19. The others showed no statistically significant difference, although they were more frequent in the group of patients with COVID-19. Conclusion: COVID-19 infection in the perioperative period of cardiac surgeries is associated with higher rates of morbidity and mortality. Delaying elective surgeries in coronavirus-positive patients can help reduce the risk of complications, along with effective strategies to decrease in-hospital infection. 108514 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Long-Term Success in Percutaneous Valve Commissurotomy - is Wilkins Score Over 9 a Definitive Limit? JOAO MIGUEL MARTINS DE CARVALHO1, Ricardo Alves Pinto1, Tania Proenca1, Joao Calvao1, Ana Filipa Amador1, Catarina Marques da Costa1, Andre Cabrita1, Catarina Marques1, Carla de Sousa1, Mariana Paiva1, Joao Carlos Silva1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao Percutaneous valve commissurotomy (PMC) is an established treatment in patients with significative mitral stenosis (MS). Although rheumatic MS incidence has decreased in the last century, it remains a prevalent pathology worldwide. The Wilkins score (WS) is a reference in echocardiographic assessment of MS; a score <=8 is considered a predictor of treatment success and score between 9 and 11 is a "grey zone" (WGZ) in which doubts persists regarding PMC success. The purpose of our study was to evaluate the early and long-term results of PMC in patients with rheumatic MS and to compare long-term events between patients with WS <= 8 and patients in WGZ. We retrospectively analysed all patients between 1991 and 2008 with significative rheumatic MS undergoing PMC. Data were collected at baseline and during long-term follow-up. MACE was defined as a composite of all-cause mortality, mitral valve re-intervention or cardiovascular hospitalization. In our cohort, 124 patients were included. Most were female (87%), mean age at the time of repair was 46 +- 11 year-old and mean follow-up was 20 +- 6 years. Before the procedure, 81% had WS <= 8 and 19% were in WGZ. Both groups had similar baseline characteristics, namely age at first intervention, NYHA class and follow-up time. All patients had preserved biventricular systolic function, 83% presented PH, mean transvalvular gradient (TVG) and mitral valve area (MVA) were 12.8 mmHg and 1.0 cm2, respectively. Most of the procedures were successful (91%) and without complications (94%). Mean MVA improvement was similar in both groups [0.9 cm2 in WS <= 8 and 0.8 cm2 in WGZ, t(102) = 0.173, p = 0.863]; there was also no significative difference in TVG and PASP reduction after PMC. During long-term follow-up, re-intervention and mortality occurred in 40% and 23% in WS <= 8 and in 50% and 29% in WGZ, respectively, and none of these differences was statistically significant (p = 0.389 and p = 0.544, respectively). Concerning time-to-event analysis, approximately 80% of patients kept uneventful and >90% alive after 10 years in both groups and no significant difference in M ACE events and all-cause mortality between WS <= 8 and WGZ was observed (Log Rank, p = 0,419 and p = 0.950, respectively). PMC was safe and effective in clinically significant rheumatic MS in both WS <= 8 and WS 9-11, with similar MVA improvement. After 10 years, approximately 80% of patients were MACE-free and >90% alive in both groups. There was no difference concerning WS groups. 108515 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Destination Therapy or a Bridge to Transplant? - Long-Term Outcome in Fontan Procedure Patients JOAO MIGUEL MARTINS DE CARVALHO1, Ricardo Alves Pinto1, Tania Proenca1, Catarina Martins da Costa1, Ana Filipa Amador1, Joao Calvao1, Catarina Amaral Marques1, Andre Cabrita1, Sofia Cardoso Torres1, Cristina Cruz1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao (CHUSJ), Porto, Portugal The Fontan procedure (FP) is considered a palliative surgical technique used for complex congenital heart disease (CHD) patients not suitable for biventricular repair. Currently, these patients' life expectation is extended but they experience high morbidity and mortality risks and their long-term management is challenging. Our aim was to evaluate the morbidity of these patients after a long-term follow-up. We collected a retrospective cohort of patients palliated with FP, that were followed in an adult CHD outpatient clinic born between 1980 and 2001. Clinical and echocardiographic data were collected. A time to adverse event analyses was performed. A total of 26 patients were enrolled, with a median follow-up of 17 years. The median age was 24 (IQR 22-30) years-old, 35% were female. As for the cardiovascular risk factors, none had hypertension or dyslipidaemia, 3,9% had diabetes and 11,5% were smokers or previous smokers. The main anatomic abnormalities that lead to the FP were single ventricle (53,8%), followed by pulmonary atresia (23,1%), double outlet right ventricle (11,5%), ventricular septal defect (3,9%) and Ebstein anomaly (7,7%). The majority of patients were previously submitted to a shunt (42,3% with a Blalock-Taussig and 19,3% with an atrial septostomy); the most prevalent surgical technique was the cavopulmonary connection (69,2% extracardiac, 15,4% intracardiac), followed by the atriopulmonary anastomosis (11,5%). The systemic ventricle was morphologically left in 84,6%. A fenestration or a residual shunt persisted in 30,8%. The mean basal oxygen saturation was of 95%, with 3,9% of patients being cyanotic. The majority of patients were asymptomatic (69,2%), with a normal ventricular function in those with a systemic left-ventricle (91,7% of patients), and a moderately impaired in those with a systemic right-ventricle (50% of patients); more than moderate AV valve regurgitation was present in 7,7%. Pulmonary hypertension was observed in 7,7%. Atrial arrythmias were present in 11,5%. Liver disease affected 50% of patients (1 patient with an hepatocarcinoma) and protein-losing enteropathy was present in 7,7%. One patient was submitted to a re-FP, due to a Fontan circulation obstruction; another patient was submitted to a heart transplant. Regarding the time-to-adverse-events analyses, more than 65% of patients were event-free during the first 15 years. However, after 20 years of FP more than 60% of patients presented with an adverse event. 108517 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cardiac Remodeling in Rats with Myocardial Infarction Submitted to Sleep Restriction BRUNNO LEMES DE MELO1, Brunno Lemes de Melo1, STELLA DE SOUZA VIEIRA1, Ednei Luiz Antonio1, Helenita A. Oliveira1, Ighor L. Teixeira1, Andrey Jorge Serra1, Paulo Jose Ferreira Tucci1 (1) Universidade Federal de Sao Paulo; (2) Faculdade de Medicina de Sao Jose do Rio Preto Introduction: Sleep is an active and heterogeneous physiological process, evolutionarily conserved, which plays a critical role in survival. It is presumed that sleep has the main function of restoring the physiological and biochemical balances that change during the waking period. It is also crucial for the tissue regeneration process and metabolism. It is known that sleep deprivation or restriction (SR) generates negative physiological effects on the body. Sleep deficit promotes patent neuroendocrine and metabolic changes in humans and laboratory animals, such as reductions in the levels of thyroid hormones, thyroid-stimulating hormones, growth hormones, and testosterone, as well as increases in adrenocorticotropin, corticosterone, adrenaline, noradrenaline, and dopamine. Added to this are the hyperactivation of the sympathetic nervous system and the stimulation of a pro-inflammatory state. These implications lead to obvious clinical repercussions, by which the cardiovascular system is also affected. Evidence indicates that the decrease in sleep hours is associated with an increased risk in the development and worsening of cardiovascular diseases (CD). Objective: To determine if SR enhances cardiac remodeling after Myocardial Infarction (MI) in male rats; to verify if the treatment with b-blocker can attenuate the damages resulting from the SR after MI. Method: Male Wistar rats were used, the animals were divided into 5 groups (SHAM:submitted to sham surgery; MI:submitted to MI; SR: submitted to SR; MISR: submitted to MI and SR; MISR+bB:IMRS treated with b-blocker), in the groups submitted to the IM technique, only animals that had infarction affected >37% of the LV. Results: The MISR group had pulmonary congestion; the MI resulted in an increase in the diastolic area (LVDA) and systolic area (LVSA) of the LV, in the SHAM and SR groups there were no significant changes. The MI group demonstrated a decrease in the LV cross-sectional area fraction (LVAF) and an increase in nuclear volume; increased LV end-diastolic pressure (EDP) values were identified in the MI and MISR groups vs. Sham and MI vs. SR. Conclusion: The use of b-blocker was effective in slowing down post-infarction myocardial remodeling under SR conditions. These effects were observed in the LVAF, PDF, and pulmonary congestion preservation data. Thus, it is concluded that the b-blocker administered under conditions of adrenergic hyperactivity caused by SR was effective in attenuating cardiac remodeling. 108525 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Effects of Cocoa Consumption on DNA Damage, Blood Pressure, Body Composition and Biochemical Parameters of Resistant Hypertensive Individuals: A Pilot Study THAIRINI DE SOUZA MIGUEL1, Leticia Machado Santos1, Jorge da Silva Pinho Junior1, Anna Paula Arpini Botelho2, Julia Passarelli Pereira2, Sergio Girao Barroso1, Glauber Monteiro Dias2, Andrea Cardoso de Matos1, Grazielle Vilas Boas Huguenin1 (1) UNIVERSIDADE FEDERAL FLUMINENSE; (2) INSTITUTO NACIONAL DE CARDIOLOGIA Introduction: Cardiovascular diseases (CVD) are the main causes of death in the world and hypertension is the main triggering factor of CVD. Some individuals are resistant to standard treatment for hypertension, and resistant arterial hypertension (RAH) is characterized. Cocoa has been shown to be a food with interesting repercussions on cardiovascular health, attenuating blood pressure, improving glycemic and lipid profile, body composition, in addition to possibly protecting against DNA damage. However, it is not yet known whether these effects are reproduced in the RAH. Objective: To investigate the effect of cocoa powder consumption on DNA damage, blood pressure, glycemic and lipid profiles and body composition in patients with RAH. Methods: Randomized, double-blind, placebo-controlled clinical trial. Twelve participants were randomized into a control group (CG = 6) or intervention group (IG = 6). The GI received 30g of cocoa powder for 60 days. The GC received 30g of maltodextrin, colored and flavored, for 60 days. Blood glucose, HbA1c, triglycerides, total, HDL and LDL cholesterol, weight, BMI, waist and hip circumference were analyzed at times T0, T30 and T60. DNA damage analysis was performed using the comet assay, at T0 and T60. Descriptive statistical analysis was performed using the GraphPad Prism software. When applicable, ANOVA test was performed. Results were presented as mean and standard error and the difference was considered significant when p <= 0.05. Results: Participants were 59 +- 8.27 years old and 58.33% were women. At T30, there was a significant decrease in HbA1c (p = 0.0531) in the IG (5.325 +- 0.3065%) compared to the CG (6.520 +- 0.3865%). We observed a trend towards attenuation of DNA damage at level 1 (T0 21.75 +- 14.73-T60 10.50 +- 5.18). This result is inverse in the placebo-supplemented group, where we observed a trend of increased damage (T0 7.17 +- 1.41-T60 14.33 +- 4.47). The other parameters studied did not change. Conclusion: Supplementation with cocoa powder, by individuals with RAH, was beneficial in reducing HbA1c levels, without altering fasting glucose. As for DNA damage analysis, cocoa supplementation seems to add some protection to DNA, at damage level 1. More studies need to be carried out to better elucidate the issues addressed in the present study. 108527 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Role of Primary Care in Controlling an Important Cardiovascular Risk Factor BRUNO GIUDICE D'AVILA1, Bruna de Matos Bauer1, Rosane Hermann2 (1) Irmandade Santa Casa de Misericordia de Porto Alegre - ISCMPA; (2) Atencao Primaria, Prefeitura Municipal de Brusque-SC Introduction: Smoking is an important isolated risk factor for cardiovascular disease and the leading cause of preventable morbidity and mortality worldwide. Such relevance has demanded from the health systems the elaboration of strategies to face this problem. This article aims to describe the successful experience of a multidisciplinary team of a Brazilian Public Health Unit in the fight against smoking during a follow-up period of 21 months. Methods: The strategy used for smoking cessation treatment involved group activities and psychosocial interventions with an emphasis on the cognitive-behavioral approach. Drug treatment with bupropion and nicotine patches was used according to medical evaluation and in accordance with the guidelines of the Brazilian Ministry of Health. A survey was carried out to evaluate users motivated to quit smoking and interested in participating in the proposed activities, in addition to evaluating the existence of cardiovascular comorbidities. The limit of up to 15 participants per group was defined. The activities were carried out in 10 sessions, the first four being weekly and the follow-up sessions after 15, 30, 60, 90 and 180 days, from February 2017 to November 2018. The actions were carried out by a team composed of a doctor, a nurse, community health agents and with the support of a nutritionist, a psychologist and a physical educator. All the professionals involved had previously completed a training course for the development of actions according to the clinical protocols and therapeutic guidelines of the Brazilian Public Health System. Results: During the study period, 54 patients were selected to participate in the activities. In this group, there was a predominance of females, a prevalence of arterial hypertension of 59% and diabetes of 18%. 74% of individuals reported at least one previous unsuccessful attempt to quit tobacco use. At the end of the observation period, 70% of the participants remained abstinent. There were 4 evasions due to change of residence territory and 12 due to resumption of tobacco use. Conclusion: This study highlights the remarkable potential of primary care in controlling one of the main risk factors for cardiovascular disease. It is possible to observe that even low-cost interventions for the Health System, as long as they are planned considering local sociocultural factors, can provide satisfactory results. 108534 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH COVID-19 on Brazil: Correlation between Socioeconomic, Demographic and Health Services Structure and Mortality and the Proposal of a Vulnerability Score LUKA DAVID LECHINEWSKI1, Lucas Henrique Olandoski Erbano1, Bruna Olandoski Erbano1, Nicolle Amboni Schio1, Raisa Natalia Dotto1, Amanda Zanlorenzi1, Lucas Baena Carstens1, Rafaela Lima Camargo1, Fernanda Leticia Perez Moraes1, Marcia Olandoski1, Jose Rocha Faria-Neto1 (1) Pontificia Universidade Catolica de Curitiba Introduction: COVID-19 pandemic rapid spread caused pressure over health systems and impaired assistance to other diseases, as observed by the reduction of acute coronary syndromes hospital admissions. In Brazil the number of cases and deaths related to COVID-19 happened quite differently through the Brazilian states (BS). Objectives: Identify socioeconomic, demographic and health structure services indices that had association with a higher death rate on the initial months of the pandemic and propose a score to identify the most vulnerable states based on these indicators. Methods: This population based ecological study analyses data from the 100th days after the first registered death for COVID-19 in the 27 BS and correlate with socioeconomic, demographic and health structure indices. The vulnerability score (VS) of COVID-19 death was composed by the indices that presented a Pearson's linear correlation >0,4. We separated the BS on 3 groups, according to the cumulative death rate/100.000 inhabitants at the 100th day after the first death in each state. Results: The indicators with higher correlation coefficient were: the number of hospital bed/100.000 inhabitants (0,61), the Social Vulnerability Index (0,52), percentage of population <40 years old (0,51), population with tap water (0,49), number of doctor/100.000 inhabitants (0,44) and life expectancy at birth (0,43); these indices built the VS. The overall correlation coefficient between the final score and the number of deaths/100,000 inhabitants on the 100th day after the first death in each state was 0.63. The correlation was 0.44 for states with higher deaths (group 1), 0.71 for intermediate profile (group 2) and 0.85 for states with lower death rates (group 3). Conclusions: Socioeconomic, demographic and mainly health structure services indices before the pandemic correlate with COVID-19 mortality. The VS proposed has good correlation with the cumulated death rate/100.000 inhabitants at the 100th day after the first death. As a underdeveloped country, identify the most vulnerable states is strategic to better allocate supplies and health investments. 108567 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Close Protocol with Center-Specific Ablation Index Target in AF Ablation TANIA FILIPA GALVAO PROENCA1, Ricardo Alves Pinto1, Miguel Martins Carvalho1, Catarina Costa1, Carlos Xavier Resende1, Pedro Diogo Grilo1, Joao Calvao1, Ana Filipa Amador1, Goncalo Pestana1, Ana Lebreiro1, Luis Adao1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao Pulmonary vein (PV) isolation is an established treatment for atrial fibrillation (AF). A contact force (CF)-guided ablation protocol respecting region-specific criteria of lesion contiguity and lesion depth ('CLOSE' protocol) has been associated with high incidence of acute durable PV isolation and a high single-procedure arrhythmia-free survival at 1 year. Differences in ablation index (AI) targets exist between centers, and its optimal value remains unknown. In the present study, we sought to evaluate the safety and outcomes of our local ablation protocol. We retrospectively analyzed 37 patients with paroxysmal AF who underwent antral PV encircling using a CF-sensing catheter in a tertiary center from January 2018 to November 2019. Radiofrequency (RF) was delivered targeting interlesion distance <=6 mm and ablation index (AI) >=380 at posterior wall and >=500 at anterior wall. Cavotricuspid isthmus (CTI) ablation was performed if previous typical atrial flutter (AFL) was documented. PV isolation was documented with exit block and the use of adenosine. Recurrence was defined as any AF, atrial tachycardia (AT), or AFL >30 s on 24-hour Holter monitoring or 12-lead ECG; or symptoms recurrence. 37 consecutive patients (70% male, median age 53 years) underwent antral PV encircling. 30 were taking antiarrhythmic drug (AAD) and 12 were submitted to previous cardioversion (11 with successful CV to sinus rhythm). Procedure and fluoroscopy time were 100 +/- 19.6 min and 5 +/- 2.0 min, respectively. Mean AI values, CF and RF time per lesion, were as follows: anterior left PVs - 490 +/- 21, 9.5 +/- 1.9 g, 32.0 +/- 5.1 sec; posterior +/- 11, 10.53.5 g, 28.8 +/- 5 sec; anterior right - 498 +/- 15, 12 +/- 2,9 g, 32.3 +/- 4.8; posterior right - 384 +/- 12, 10.3 +/- 2.2 g, 27.9 +/- 3.1 sec. Incidence of first-pass and adenosine-proof isolation were 97% and 95%, respectively. Touch up lesions were applied to ensure isolation, with 100% success at the end of the procedure. CTI ablation was performed sucefully in 22%. 76% were discharged on AAD and 24% maintained AAD at one-year follow-up. At 12 months, single-procedure freedom from recurrence was 89%. Only one patient had an acute complication, a femoral haematoma that solved with local compression. Our experience with "CLOSE" protocol with specific AI target supports that an ablation respecting the referred predefined criteria for lesion depth and contiguity results in safe and efficient outcomes. 108570 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocarditis, Pericarditis and COVID-19 Vaccination - a True Concern? TANIA FILIPA GALVAO PROENCA1, Ricardo Alves Pinto1, Miguel Martins Carvalho1, Filipa Amador1, Catarina Costa1, Joao Calvao1, Andre Cabrita1, Catarina Marques1, Ana Pinho1, Luis Santos1, Paula Dias1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao Myocarditis and pericarditis are inflammatory diseases affecting 1 to 10 persons in 100 000 persons/year. Anti-SARS-Cov-2 vaccines are being widely used worldwide, and concerns about its association with a higher risk of cardiac inflammatory syndromes are being raised. We compare the prevalence and severity of myocarditis and/or pericarditis admissions before and after Covid-19 vaccination. We retrospectively analysed all patients admitted to a Cardiology Department due to myocarditis and/or pericarditis during COVID-19 pandemic and compared the clinical data between two 10-months periods, before and after Covid-19 vaccination. Pre-vaccination period (PVp) was defined from March to December 2020 and vaccination period (VCp) from January to October 2021. A total of 23 patients were enrolled, 12 in PVp and 11 in VCp, with a median age of 28 (IQR 22-43) year-old. Of total, 44% had perimyocarditis, 30% myocarditis and 26% pericarditis. In VCp there was significatively more man admitted (50% vs 90%, p = 0.019). Concerning clinical data, the two periods were similar. Median CRP was 68 mg/L and, in perimyocarditis or myocarditis, median high-sensitivity troponin I and BNP were 10 250 ng/L and 38 pg/mL, respectively. The majority of patients had ECG abnormalities, mostly ST-elevations (39%) and repolarization abnormalities (20%). At presentation, left systolic function was preserved in all patients in PVp group, while 27% had mildly to moderate reduced ejection fraction in VCp (p = 0.052); all of them improved to normal function. Of the 17 patients with myo or perimyocarditis, 14 were submitted to MRI (median 6 days after the event): 60% had high signal intensity in T2 weighted sequences suggestive of oedema and 73% had LGE enhancement compatible with myocarditis. Median left and right ventricular ejection fraction by MRI were both 61%. In VCp group, 55% of patients were previous vaccinated (3 patients with mRNA-1273, 1 with BNT162b2 and 2 with JNJ-78436735 vaccines). The median time between last vaccine administration and event was 73 days (2-112). In VCp group performing cardiac MRI, 40% of vaccinated patients had LGE enhancement (p = 0.038). There was no difference in the incidence of patients admitted. During two equal periods before and after Covid-19 vaccination, there was no difference in the incidence of patients admitted with myocarditis and/or pericarditis. Curiously patient with previous Covid-19 vaccination exhibited less LGE-enhancement on cardiac MRI. 108605 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Innovations in Telecardiology: Activities Developed by Nursing Residents in a Reference Hospital in the State of Pernambuco TAYNE FERNANDA LEMOS DA SILVA1, Larissa dos Santos Brandao1, Raquel Maria Alexandre da Silva1, Maria Tayna Silva Feitosa1, Monaliza Evelyn Pereira de Sousa2, Gislainy Thais de Lima Lemos1, Rodrigo Manoel do Nascimento2, Dara Stephany Alves Teodorio2, Hortensia Paula Bernardino Ribeiro1, Renata Santos de Oliveira3, Dulcineide Goncalo de Oliveira3, Simone Maria Muniz da Silva Bezerra4 (1) Enfermeira Especialista em Cardiologia pelo Pronto Socorro Cardiologico de Pernambuco - PROCAPE/UPE; (2) Residente de Enfermagem em Cardiologia Uniprofissional e Multiprofissional do PROCAPE/UPE; (3) Nucleo de Saude da Secretaria Estadual de Saude de Pernambuco - NET-SES/PE; (4) Coordenadora do Programa de Residencia Uniprofissional e Multiprofissional em Cardiologia do PROCAPE/UPE Introduction: In Brazil, cardiovascular diseases account for 30% of all deaths, with about 1,000 deaths per day. In 2017, the Ministry of Health (MS) launched a projector called National Telediagnostic Offer, expanding the remote diagnosis service to the poorest areas of Brazil.2 The Telecardiology Network of Pernambuco aims to meet the demands on the Clinical Management of Cardiovascular Diseases in its municipalities, with the issuance of online electrocardiogram reports (Tele-ECG) and teleconsultations. This network works in partnership with a multiprofessional residency program of a hospital recognized by the MS as one of the four cardiology reference institutes in Brazil, located in the state of Pernambuco. Objective: To describe the results of the activities carried out by nursing residents in cardiology in a referral hospital in the State of Pernambuco. Methods: This is a descriptive, observational study based on the activities carried out by nursing residents of a multiprofessional program in cardiology, from March 2020 to February 2022. Results: During the cardiology residency program, nurses had the opportunity to be pioneers in Teleassistance in cardiology services, in partnership with the Pernambuco State Health Department (SES-PE). The following were implemented: Telemedicine-based service for the follow-up and monitoring of patients treated with anticoagulant therapy and the Tele-ECG service in primary health care in the municipalities of Pernambuco. The residents established the outpatient department flowchart and carried out training for the multidisciplinary team. Up to now, 8,712 teleconsultations were performed from June 2020 to February 2022, and of these, 3,202 were performed by nursing residents. In the Tele-ECG service, from 185 municipalities, 56 (30.3%) are already issuing electrocardiogram reports and 52 (28.1%) are still in the implementation period. In total, 14,349 reports were issued (from October 2020 to March 2022), of which 14,121 had been classified as an elective electrocardiogram and 122 as an emergency report. Therefore, the joint work of the multiprofessional residency program and the SES-PE constitutes a success when considering the high productivity attained by the project so far and assuring the access of patients from the countryside of Pernambuco to specialized cardiology services. 108577 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Twenty-Years After Percutaneous Mitral Commissurotomy in Women with Mitral Valve Stenosis TANIA FILIPA GALVAO PROENCA1, Ricardo Alves Pinto1, Miguel Martins Carvalho1, Joao Calvao1, Ana Filipa Amador1, Catarina Costa1, Catarina Marques1, Andre Cabrita1, Catia Oliveira1, Mariana Paiva1, Joao Carlos Silva1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao Rheumatic fever in childhood used to be the major cause of valve disease in women. Despite the reduction in its incidence, nowadays rheumatic mitral stenosis (MS) remains an important healthcare problem. We retrospectively analysed all women with clinically significant rheumatic MS submitted to percutaneous mitral commissurotomy (PMC) between 1991 and 2008 and compare long-term events between patients with and without pulmonary hypertension (PH). A total of 108 women were enrolled, with a mean age at the time of PMC of 46 +- 11-year-old and a median follow-up of 21 (IQR 17-26) years. Before the procedure, all patients had preserved biventricular systolic function; 86% presented PH, median transvalvular gradient (TVG) and mitral valve area (MVA) were 12.0 mmHg and 1.0 cm2, respectively, Most of PMC were successful (91%) and without major complications (94%), with a median MVA improvement of 0.9 cm2 and reduction of 9.0 mmHg in TVG and 8.0 mmHg in pulmonary artery systolic pressure (PASP). During long-term follow-up, 43% of patients were submitted to re-intervention (most of them surgically) and 25% died. In patients non-submitted to re-intervention, TVG and PASP remained similar with early post-procedure evaluation (p = 0.241 and p = 0.964, respectively), while MVA reduced over time, yet still statistically superior to baseline MVA (1.5 cm2 vs 1.0 cm2, p < 0.001). Concerning time-to-event analysis, approximately 80% of patients kept uneventful after 10 years; after 30 years, more than 20% continued MACE-free and almost 50% were alive. Regarding PH presence at time of PMC, there was no significant difference in MACE events and all-cause mortality (Log Rank, p = 0,711 and p = 0.689, respectively). PMC was safe and effective in clinically significant rheumatic MS in women. 108585 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Noacs Safety and Efficacy in Adult Congenital Heart Disease RICARDO JORGE DOS REIS ALVES PINTO1, Miguel Martins Carvalho1, Tania Proenca1, Catarina Costa1, Ana Filipa Amador1, Joao Calvao1, Catarina Marques1, Andre Cabrita1, Catia Oliveira1, Cristina Cruz1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao, Porto, Portugal Introduction: Adult Congenital Heart Disease (ACHD) patients are an increasing population with known high risk for thromboembolic events. Validated scores as CHA2DS2-VASc and HAS-BLED are uncertain in this population. Although apparently safe, data is scarce about the use of non-vitamin K oral anticoagulants (NOAC) in this population. Its use remains off-label and more studies are warranted. Purpose: To evaluate all patients on-NOAC followed in an ACHD outpatients clinic and observe its safety and efficacy in thromboembolic prevention during a median follow-up of 34 months (IQR 7-60 months). Major bleeding was defined according to types 3 to 5 in Bleeding Academic Research Consortium (BARC) scale. Adverse event was defined as at least one of the follows: death, stroke, myocardial infarction, systemic embolism or major bleeding. Results: A total of 65 patients on NOAC were included, with a mean age of 52 +- 14 year-old, 66% were female. Most frequent ACHD were atrial septal defect (22%) and tetralogy of Fallot (TOF, 22%), followed by atrioventricular septal defect (17%) and transposition of great arteries (9%). Regarding cardiovascular risk factors, 37% had hypertension, 23% had dyslipidaemia, 9% had diabetes, 8% were smokers or previous smokers and 23% had obesity. Most patients had preserved biventricular function, 20% presented systemic ventricle systolic dysfunction and 12% subpulmonic ventricle systolic dysfunction. Atrial fibrillation or atrial flutter (AF/AFL) were the major reasons for anticoagulation (94% of patients); the remaining were on NOAC due to previous ischaemic stroke, intra-cardiac thrombus or deep venous thrombosis. At the time of NOAC initiation, 49% of patients had a CHA2DS2-VASc score >=2 (median 1, IQR 1-3) and median HAS-BLED score was 0 (IQR 0-2); 43% were medicated with apixaban, 29% with rivaroxaban, 22% with edoxaban and 6% with dabigatran. During a median follow-up of 34 months, none of the patients had ischaemic complications or major bleeding and one patient died after pulmonic prothesis dysfunction surgery. Concerning time--event analysis, all patients kept uneventful after 2 years and more than 95% continued event-free after 8 years on-NOAC. Conclusion: In an ACHD population on-NOAC, the major reason for anticoagulation was AF/AFL. After a long-term follow-up, most patients maintained event-free after 8 years. This report highlights the safety and effectiveness of NOAC in ACHD patients. 108588 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Development of Low-Cost Multiplex SNP Genotyping Methodologies for Association Studies Related to Cardiovascular Risk YASMIN LEMOS ROLLEMBERG CRUZ MACHADO2, Gizella da Cunha Rodrigues1, Rossana Ghessa Andrade de Freitas2, Maria Eliane Campos Magalhaes2, Ricardo Mourilhe-Rocha2, Andrea Araujo Brandao2, Denilson Campos de Albuquerque3, Dayse Aparecida da Silva1 (1) Roberto Alcantara Gomes Biology Institute, Rio de Janeiro State University (UERJ); (2) Faculty of Medical Sciences, Rio de Janeiro State University (UERJ); (3) Department of Cardiology, Pedro Ernesto University Hospital/Rio de Janeiro State University (UERJ) Introduction: The role of genetic variants in multifactorial diseases has been widely investigated through genome-wide association studies, mainly replicated in genetically homogeneous populations. However, the replication of such associations in smaller assays requires an alternative molecular methodology more accessible to the scientific community as a whole. Customized Multiplex assays including informative genetic markers offer a single, low-cost and practical option. Aim: To develop a cheaper Multiplex methodology based on SNaPshot(r) technology for genotyping 21 SNPs clinically relevant in genome-wide studies and their application in clinical samples from an admixed population. Methodology: Four custom Multiplex Panels involving 21 SNPs in genes related to cardiovascular risk factors were constructed for genotyping 1,064 buccal swabs and 528 blood samples, differently preserved. The resulting genotypes were validated by Sanger sequencing. Results: The full genetic profile was achieved in 72-92% among the panels considering both swabs and blood samples. Marker's performance ranged from 81-100%. Panels reached above 90% of confident genotyping calls in samples stored for 2 years or more, regardless of their type. The agreement rate between genotyping methods ranged from 97.5-100%. Conclusion: The customized Multiplex Panels represented an efficient molecular methodology to genotype SNPs with high sensitivity, efficiency, and low cost from different biological samples stored for years. 108608 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Hospitalizations for Acute Myocardial Infarction in Children and Adolescents in the Last 10 Years in Brazil MATHEUS AKIRA SUZUKI DE OLIVEIRA1, Matheus Akira Suzuki de Oliveira1, Julia de Avila Gutierrez2, Hildeman Dias da Costa1, Luiz Felipe Facanha Ramos3, Karen Tassia Facanha Ramos3, Mathews Barbosa Santiago5, Leo Christyan Alves de Lima4 (1) Universidade Federal de Rondonia; (2) Centro Universitario Aparicio Carvalho; (3) Universidade Federal do Amapa; (4) Centro Universitario Sao Lucas; (5) Centro Universitario Uninorte Introduction: Acute myocardial infarction is a pathology that affects all age groups and should be prevented even in less common age groups, such as children and adolescents, in order to reduce morbidity and mortality rates. The points to be observed are care with the prevention of cardiac risk, and the adoption of healthy lifestyle habits throughout childhood. Objective: To describe the epidemiological profile of hospitalizations for acute myocardial infarction among children and adolescents in Brazil between 2012 and 2021. Methods: Cross-sectional epidemiological study. Data were obtained from the informatics department of the unified health system - DATASUS. The variables studied were: total number of hospitalizations, sex, color/race, deaths and mortality rate. The age group surveyed was individuals from zero to 19 years old. The period was delimited between 2012 and 2021. Results: 2,542 hospitalizations were recorded. Males reported 1,472 hospitalizations. The brown color/race registered 867 hospitalizations. The most affected age group was adolescents between 15 and 19 years old, with 1,182 hospitalizations. The total number of deaths was 172. The average mortality rate in the period was 6.77. Conclusions: The epidemiological profile of hospitalizations was characterized by brown adolescents aged between 15 and 19 years. The reduction in the number of hospitalizations in 2020 and 2021 may have been influenced by the COVID-19 pandemic. 108617 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Association between Lung Ultrasound Findings, SCAI Shock Classification and Clinical Outcomes in Patients with ST Segment Elevation Myocardial Infarction GUILHERME PINHEIRO MACHADO1, Fernando Luis Scolari1, Gustavo Neves de Araujo3, Alan Pagnocelli1, Angelo Chies2, Marco Vugman Wainstein2, Rodrigo Vugman Wainstein1 (1) Hospital de Clinicas de Porto Alegre (HCPA); (2) Universidade Federal do Rio Grande do Sul (UFRGS); (3) Imperial Hospital de Caridade Background: Incidence and mortality in cardiogenic shock (CS) remains high despite current management. Improvements in early diagnosis and risk stratification are warranted in order to prevent CS in ST segment elevation myocardial infarction (STEMI). Objectives: Our aim is to evaluate the association between pulmonary congestion evaluated by lung ultrasound (LUS), Society for Cardiovascular Angiography and Interventions (SCAI) shock classification and clinical outcomes in patients admitted with STEMI. Methods: Prospective cohort study of STEMI patients treated in a tertiary care hospital in Brazil. LUS was performed immediately before coronary angiography. Development of cardiogenic shock in the first 24 hours and in-hospital mortality were retrospectively evaluated. Results: A total of 582 included patients. Mean age was 61 +- 12 years and 373 (64.1%) were male. After 24 hours of admission, SCAI shock stage A was present in 361 (62%) patients, while 115 (19.8%) were class B, 44 (7.6%) class C, 58 (10%) class D, and 4 (0.7%) class E. There was an association between increasing number of positive LUS zones and the SCAI shock classification (P < 0.001). We also found strong association between number of positive zones in lung ultrasound and CS (OR = 1.4 (95% CI 1.3-1.5, P < 0.001), SCAI shock stages (OR 1.3 (95% CI 1.2-1.4, P < 0.001) and in-hospital mortality (OR 1.3 (95% CI 1.2-1.4, P < 0.001). Additionally, presence three or more positive LUS zones was associated with increased mortality, P (log-rank) < 0.001. Conclusions: Lung congestion evaluated by admission LUS was significantly associated with increment in SCAI shock stage, development of CS and in-hospital mortality in STEMI patients. 108636 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Cardiac Arrest on Persons Under the Age of 20, from 1996 to 2019 THAYANNE MENDES DE ANDRADE1, Mariara Lopes da Costa Marques1, Sofia Almeida Guerra1, Thais Rocha Salim1, Glaucia Maria Moraes de Oliveira1 (1) Universidade Federal do Rio de Janeiro (UFRJ) Introduction: Cardiac arrest (CA), in pediatrics, has high mortality and severe neurological sequelae. Information on the causes and mechanisms of death in children under 20 can provide theoretical support for improving health in childhood and adolescence. Objectives: To carry out a population analysis of mortality rates (MR) from basic and multiple causes of death, in children under 20 years of age, of both sexes, from 1996 to 2019, and to identify the frequency of description of CA in death certificates (DC) of these individuals and their places of occurrence, to promote strategies to improve the prevention of deaths. Method: An ecological time-series study, from 1996 to 2019, of children deaths under 20 years of age, in which MR and we evaluated proportional mortality (PM) due to underlying cause of death. We analyzed the percentage of CA description in the DC (any lines) and the place of occurrence. Also, we described MR per 100,000 inhabitants and PM due to underlying cause of death under 20 years of age, by sex, and age group. The percentages of death from underlying causes were calculated when CA was described in any line of parts I and II of the DC, by age groups, and the percentages of death from underlying causes, according to their place of occurrence. Data were taken from DATASUS, IBGE and SINASC. Results: In Brazil, from 1996 to 2019, there were 2,151,716 deaths in children under 20 years of age, with a MR of 134.38 per 100,000 inhabitants, with higher death rates among male neonates. Two hundred forty-nine thousand three hundred thirty-four had CA described in any DC line, corresponding to 11.6% of these deaths. We defined four patterns for the underlying cause of death when CA in the death sequence. In the neonatal period, perinatal causes; in children under five years, respiratory system diseases; 5 to 14 years, neoplastic and hematological; and in adolescents aged 15 to 19, external causes. The central place of occurrence of these deaths was in the hospital. Conclusion: The highest MR of underlying causes of death, in those under 20 years of age, in Brazil, from 1996 to 2019, was due to perinatal and external causes. When we evaluated multiple causes of death, the leading underlying causes of CA were respiratory, hematological, and neoplastic diseases, with higher in-hospital mortality. It is crucial to understand deaths sequence events and implement teaching strategies to pediatric cardiopulmonary resuscitation. 108644 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Patients' Perception of Educational and Musical Nursing Intervention Before Emergency Cardiac Catheterization LETICIA DE CARVALHO BATISTA1, Maria Do Perpetuo Socorro de Sousa Nobrega1, Marina de Goes Savetti1, Rita de Cassia Gengo e Silva Butcher1 (1) School of Nursing University of Sao Paulo Objective: To evaluate the experience and acceptability of an educational and musical nursing intervention to reduce anxiety in patients undergoing unscheduled catheterization. Method: Qualitative study was carried out in a highly specialized cardiology hospital in the city of Sao Paulo. In the study, 15 patients diagnosed with the acute coronary syndrome were treated and submitted to unscheduled catheterization at the emergency unit. All patients received the nursing intervention, consisting of a musical and educational component called Education and Music Intervention to Reduce Anxiety (EMIRA), prepared according to the methodological framework of complex intervention by Sidani and Braden. The interviews were recorded, transcribed, and analyzed according to Bardin's content analysis. Data collection took place from October to September 2021. Results: The analysis of the interviews allowed the grouping into three categories, 1) EMIRA Intervention: a new experience that helps reduce anxiety; 2) EMIRA intervention: an experience that generates satisfaction; and 3) EMIRA Intervention: anxiety alleviating experience. Participants have suggested using EMIRA to promote a feeling of relaxation and satisfaction. Conclusion: EMIRA seems to be an acceptable and potentially relaxing intervention for patients awaiting unscheduled catheterization in the emergency department. 108674 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Prevalence of Reduced Left Ventricular Ejection Fraction in the Brazilian Amazon Basin and Diagnostic Usefulness of B-Lines by Lung Ultrasound LUAN OLIVEIRA MATOS1, Anna Engell Holm2, Laura C Gomes3, Alma Wegener2, Karine O Lima1, Molly Dam Kaagaard2, Isabelle V. M. Vieira1, Claudio Romero Farias Marinho3, Rodrigo Medeiros de Souza1, Tor Biering-Sorensen2, Odilson M Silvestre1, Philip Brainin1 (1) Universidade Federal do Acre; (2) Herlev-Gentofte Hospital; (3) University of Sao Paulo Background: B-lines by lung ultrasound (LUS) indicate presence of extravascular lung water and has been associated with reduced left ventricular ejection fraction (LVEF) in patients with heart failure. We aimed to describe the prevalence of reduced LVEF in a community sample without a history of heart failure and to evaluate the usefulness of B-lines by LUS in this setting. Methods: In a cross-sectional study we examined a random sample of adults (>=18 years) from a community in the Northwestern part of the Brazilian Amazon (June-December 2020). All participants underwent state-of-the art echocardiographic image acquisition and 8-zone LUS by a medical doctor. No patients had known heart failure, recent chest trauma or clinical signs of infectious disease. Reduced LVEF was determined by Simpson's biplane method and defined as <45%. We assessed the mean of B-lines across all zones. Logistic regression models were applied to investigate reduced LVEF and B-lines. Results: A total of 551 participants were included (39% men, mean 41 +- 15 years) who had a mean LVEF of 57 +- 5%. From this group 16 (3%) had LVEF <45%, corresponding to a prevalence of 29/1000 adults with reduced LVEF. Participants with reduced LVEF were older, had higher blood pressure and more frequently smoked. Number of B-lines by LUS was significantly higher among participants with reduced LVEF compared to those with normal LVEF (mean B-lines 4 vs 1, P = 0.002. In logistic regression models, adjusted for clinical and cardiovascular risk factors, presence of a single B-line was associated with 1.18 higher odds of having reduced LVEF (95%CI 1.06-1.31, P = 0.002). Conclusion: The prevalence of reduced LVEF was 29/1000 adults in a community from the Amazon Basin without a known history of heart failure. B-lines by LUS were significantly more present in participants with reduced LVEF. As LUS is feasible in resource limited settings, may be conducted by non-medical personnel and by the use of handheld devices, this may be useful to identify patients with reduced LVEF in rural communities where echocardiography is not available. 108747 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Neutrophil Peptidylarginine Deiminase 4 is Essential for Detrimental Age-Related Cardiac Remodeling and Dysfunction in Mice STIJN VAN BRUGGEN1, Sirima Kraisin1, Jore Van Wauwe1, Paolo Carai1, Thilo Witsch2, Kimberly Martinod1 (1) Centre for Vascular and Molecular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; (2) Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; (3) Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland Increasing age is the highest risk factor for cardiovascular disease and heart failure (HF) development, and HF is a leading cause of death in the elderly. In our study, we aimed to investigate the specific role of neutrophils and neutrophil extracellular traps (NETs) on cardiac remodeling and decreasing function with increasing age. For this, neutrophil-specific PAD4 deletion (Ne-PAD4-/-) mice were created and aged for 2 years together with their littermate controls (WT). After 2 years we could clearly identify a decrease in both systolic (LVEF) and diastolic (E/A ratio) cardiac function in WT mice, while this age-dependent cardiac dysfunction was absent in Ne-PAD4-/- mice. In addition, cardiac function of old Ne-PAD4-/- mice was comparable to young controls. In order to explain this decreased function, hearts were evaluated histologically which showed an increase in cardiac collagen deposition in old WT as compared to old Ne-PAD4-/- mice. Additionally, we found increased levels of circulating CXCL-1, a chemokine responsible for neutrophil recruitment to sites of inflammation in old WT mice, as well as increased levels of plasma IL-6. From this we can conclude that neutrophil PAD4, and in extension likely NETs, are essential for age induced cardiac remodeling, possibly through the increased recruitment of additional neutrophils to the heart, in response to an elevated state of chronic inflammation, which is the case during natural aging. 108681 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Clinico-Epidemiological Profile of Cardiac Admissions at a District Level Hospital in South Africa: A Cohort Study LILLIAN LIZE ENGELBRECHT (MARRIED SURNAME: GILES)1, Nasief van der Schyff3, Mark Engel1 (1) University of Cape Town (UCT); (2) Groote Schuur Hospital (GSH); (3) Victoria Hospital Wynberg (VHW) Introduction: Sub-Saharan Africa (SSA) is experiencing a change in its pattern of disease prevalence, and it has been projected that non-communicable diseases (NCD) will overtake infectious diseases by the year 2030. Despite the fact that more than 80% of deaths from NCD's worldwide are estimated to occur in low-and middle-income countries, the majority of available research is from first world countries. Due to SSA's own rich genetic, geographic, social and cultural diversity, this available first world research is not applicable to our context, highlighting the need for more relevant local studies. Objectives: To better understand the clinical and epidemiological characteristics of patients admitted with cardiac disease in our district, in order to inform and guide relevant clinicians and policymakers. Methods: We conducted a retrospective records review of all patients admitted with a primary cardiac diagnosis to a district level hospital in South Africa between 1 September 2020 to 30 November 2020. Results: Our final analysis is still in progress, but we can report some preliminary findings at this time. During the three month period, we collected data from 236 cardiac admissions at our district-level, 52 medical bed, hospital. The age of patients ranged from 22 to 95, with a mean age (standard deviation) of 60 (+-14.79) years. The length of stay ranged from under 24 hours, up to 26 days, with a median length of 3 days. Hypertension (76%), Smoking (55%), and Diabetes (42.7%) were the top 3 cardiovascular risk factors noted. More than a third of diabetic patients (36.2%) had a glycated haemoglobin (HbA1c) of greater than 10.1%. Acute decompensated heart failure (45.8%) and acute coronary syndromes (40.1%) were responsible for the vast majority of admissions. Admissions were most often precipitated by prior inadequate therapy (29%), defaulting medication (17.8%) or uncontrolled hypertension (14.8%). There was a 6.7% readmission rate noted during the three month period. The inpatient mortality rate was 7.8%. Conclusion: This study showed that cardiovascular disease (CVD) can affect a wide range of ages, and reiterated the well known link between CVD and hypertension, smoking and diabetes. Poorly controlled hypertension was the third most common precipitant for admission, and a third of diabetic patients had poor glycaemic control, highlighting important areas for intervention in order to reduce the readmission and mortality rate. 108688 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSIOTHERAPY Effectiveness of Structured Exercise Program on Insulin Resistance and Quality of Life in Type 2 Diabetes Mellitus - a Randomized Controlled Trail SAMPATH KUMAR AMARAVADI1, G Arun Maiya1 (1) Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, India; (2) Department of Physiotherapy, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates. Background: Impaired glucose control & Insulin resistance are reported to be risk factors for the development of cardiovascular diseases. In the Indian population, Insulin resistance is one of the strong reasons for altered glycemic control, even though exercise training is found to be effective in glycemic control along with standard medical care. There is a dearth of literature on the effectiveness of exercise training on insulin resistance and quality of life in patients with Type 2 diabetes mellitus. Objective: To determine the effects of a structured exercise program on insulin resistance, glycaemic control, functional capacity, and quality of life in patients with Type 2 diabetes mellitus. Design: Randomized, controlled trial. Setting: Diabetic Foot Clinic, Department of Physiotherapy & Department of General Medicine, Kasturba Hospital in Manipal, Karnataka, India. Participants: 160 participants aged between 30-65 years with Type 2 diabetes mellitus. Intervention: A set of structured exercise programs (aerobic, resistance, and combined) along with the standard hospital care was performed 3-5 times weekly for 12 weeks. Measurements: Primary outcome measures: Fasting Insulin Level, Homa-IR, Six-minute walk test (6MWT), and WHOQOL-BREF questionnaire at baseline and 12th week. Secondary outcome measures: Body composition analysis, Fasting Blood Sugar, Postprandial Blood Sugar, Glycated Hemoglobin (HbA1c), and GPAQ questionnaire at baseline and 12th week. Results: The mean age of the participants in the study group was 56.05 +- 8.77 and the control group was 53.90 +- 10.20, the mean duration of diabetes in the study group was 12.74 +- 8.67 years and the control group was 11.46 +- 5.11 years, mean body mass index 25.32 +- 3.16 in the study group and 26.27 +- 3.63 in the control group. Significant differences have been observed in Homa-IR (p = <0.001), Fasting insulin (p = <0.001), Fasting blood sugar (p = <0.001), Postprandial blood sugar (p = <0.001), Glycated hemoglobin (p = <0.001), WHOQOL-BREF (p = <0.001), Six-minute walk test (p = <0.001) in the study group when compared with the control group. Conclusion: In the present study, we found that a 12-week structured exercise training program is effective in decreasing insulin resistance and improving the quality of life in type 2 diabetes mellitus. We also found that a 12-week structured exercise training program is effective on functional capacity and glycemic control in type 2 diabetes mellitus. 108714 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY New Rock Inhibitor Improves Cardiovascular Function and Pulmonary Artery Remodelling in Pulmonary Arterial Hypertension TADEU LIMA MONTAGNOLI1, Jaqueline Soares da Silva1, Bruna de Souza Rocha1, Bianca dos Santos Carlos do Nascimento1, Bruno Eduardo Dematte1, Gabriel Fonseca Gomide1, Carlos Alberto Manssour Fraga1, Gisele Zapata Sudo1 (1) Universidade Federal do Rio de Janeiro Background: Pulmonary arterial hypertension (PAH) is characterised by increased pulmonary arterial pressure and vascular thickening, which ultimately leads to right ventricle (RV) failure. Current therapies lack efficacy in preventing disease progression and lead to poor survival of patients at moderate-to-high risk. Rho-activated protein kinases (ROCK) play a key role in smooth muscle contraction and proliferation and cardiomyocyte hypertrophy and survival, and ROCK inhibitors are potential candidates for treatment of PAH. This study assesses the efficacy of a new ROCK inhibitor, LASSBio-2065, on cardiac and vascular function of monocrotaline (MCT)-induced PAH in Wistar rats. Methods: PAH was induced after a single intraperitoneal injection of 60 mg/kg monocrotaline (MCT). After 2 weeks, PAH was confirmed by Doppler echocardiography and rats were randomly divided in groups (n = 6) and treated with vehicle or LASSBio-2065 (60 mmol/kg/day, i.p.) for 14 days. Wistar rats which received a single saline injection and treated with vehicle were used as controls. At the end of treatment, hemodynamics and cardiac function were evaluated by echocardiography and RV catheterization and tissues were collected for histologic and morphometric analysis. Data was analysed by One-way ANOVA followed by Dunnett post-test and presented as mean +- standard error. Results: LASSBio-2065 reduced the pulmonary acceleration time-to-total ejection time ratio (26.7 +- 2.0 vs. 21.7 +- 1.6; p < 0.05) and increased RV output (64.2 +- 6.1 vs. 39.1 +- 8.0; p < 0.05), thus alleviating pulmonary vascular resistance and RV afterload. Arterial and cardiac remodelling were prevented by LASSBio-2065, as indicated by reduced medial wall thickness of distal pulmonary arterioles (60.7 +- 1.1 vs. 68.5 +- 3.9; p < 0.05), short axis RV-to-left ventricle (LV) internal area (85.8 +- 11.4 vs. 115.2 +- 17.8; p < 0.05) and RV Fulton index of hypertrophy (44.8 +- 2.3 vs. 55.6 +- 2.3; p < 0.05). The new ROCK inhibitor also improved the RV diastolic function, restoring both RV end-diastolic pressures (5.3 +- 0.8 vs. 11.1 +- 1.9 mmHg; p < 0.05) and Tau (16.9 +- 2.2 vs. 27.1 +- 2.8; p < 0.05) to control levels. Echocardiographic analysis revealed no significant changes in heart rate and LV diastolic and systolic functions between control and PAH groups (p > 0.05). Conclusions: The data demonstrate that LASSBio-2065 significantly improves RV function and cardiovascular histology in PAH. 108722 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Syncope by Intermitent Av-Block with Normal Electrophysiologycal Study Treated with Cardioneuroablation JOSE MIGUEL CAYO MONTES1, JOSE MIGUEL CAYO MONTES1, JOSE CARLOS PACHON MATEOS2, JUAN PACHON MATEOS1, JUAN CARLOS ZERPA ACOSTA1, ENRIQUE I. PACHON MATEO1 (1) HOSPITAL DO CORACAO; (2) SEMAP Introduction: Functional atrioventricular block (BAV) can generate pre-syncope and syncope to the point of compromising patients' quality of life, and pacemaker implantation does not resolve the condition in some cases, it is important to clarify the diagnosis, especially in young and without structural heart disease. Objective: To perform cardioneuroablation (CNA) of the parasympathetic cardiac ganglia to modulate the vagal influence on the heart and thus eliminate the cardioinhibitory response on the AV Node, treating syncope due to functional BAV, as an alternative therapy to pacemaker implantation. Methods: CNA was performed in 8 patients under 50 years of age, who had syncope due to BAV, normal electrophysiological study and positive atropine test. The mapping of the parasympathetic ganglia, the neuromyocardial interface and the mapping of AF nests was performed with the Navix-St-Jude system. These regions and those anatomically related to the 4 ganglia were treated with endocardial radiofrequency (RF) ablation. Extracardiac vagal stimulation (ECVS) is used for the end point of the procedure, demonstrating the absence of parasympathetic activity on the sinus node and AV node, proving vagal denervation in these structures. Results: Imediate and persistent increase in heart rate was observed after CNA (HR = 61, final HR = 78 bpm), Wenckebach point increase (PW:100->148 ppm) p: < 0.05. In the short and long term follow-up (after 05 years) the patients had no more syncope episodes. Holter monitoring performed at 03 months of follow-up in these patients did not record pauses or BAV, and the R-R variability was predominantly sympathetic (SDNN = 30 ms). Conclusion: Syncope and normal EPS may be caused by functional origin; Functional AV block may be treated by Cardioneuroablation without pacemaker implantation; Extracardiac vagal stimulation was fundamental to evaluate the CNA step by step. 108734 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Prevalence of Contrast-Induced Nephropathy in Cardiopathy Patients from a Hemodynamics Sector GABRIELA STOCHERO1, Gabriela Stochero1 (1) Unimed Noroeste/RS Introduction: Contrast-induced nephropathy (CIN) represents a form of acute kidney injury that occurs in patients undergoing diagnostic and therapeutic medical procedures using iodinated contrast. In the last decade, CIN has been identified as the third leading cause of acquired acute renal failure (AKI) in hospitalized patients, reaching 12% of cases. CIN is defined as an absolute increase in serum creatinine >=0.5 mg/dL or a relative increase of 25% from baseline creatinine within 24 to 72 hours after exposure to the contrast agent and in the absence of an alternative cause. Objective: To determine the prevalence of CIN in patients with heart disease undergoing diagnostic and/or treatment angiographic procedures. Method: Prospective, quantitative study carried out in the hemodynamics department of a large hospital located in the northern region of Rio Grande do Sul, Brazil. To determine the sampling of this research, a sample size calculation was performed, with an error of 5%; confidence level 90%; population 253 patients, maximum percentage of CIN 12%, totaling 79 individuals. Results: The sample consisted of 52 (65.8%) men and 27 (34.2%) women. The mean age was 65.9 +- 9.52 years. No patient in the study underwent dialysis therapy, at least 72 hours after contrast use. The prevalence of contrast-induced nephropathy was 30.38%, totaling 24 patients. It was identified that 51 (64.6%) patients who underwent contrast-enhanced procedures did not receive prophylactic measures related to the prevention of CIN, while 28 (35.4%) received hydration with saline solution (SF) 0.9% intravenously. The volume of contrast used ranged from 50 to 500 mL, with a mean volume of 171.97 +- 91.27 mL. Comparing patients with and without CIN, patients who developed nephropathy were more hypertensive, had a higher percentage of reduced left ventricular ejection fraction and a higher incidence of heart failure. Patients who developed CIN had more complications after the procedures, corresponding respectively to 25% (n = 6) versus 3.6% (n = 2); (p = <= 0.001). Conclusion: A high prevalence of contrast nephropathy was evidenced, despite the patients having few risk factors, which highlights the need for preventive measures and reduction of the volume of contrast. 108749 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Barriers to Maintaining an Aerobic Exercise Routine (AER) for People Living with Prediabetes and Diabetes: Six-Month Follow-Up ANA PAULA DELGADO BOMTEMPO BATALHA1, Josiane Aparecida de Almeida3, Isabela Coelho Ponciano3, Dara Marilia Damasceno2, Ana Carolina Oliveira Pierangeli Vilela2, Tamara Rafino de Castro2, Ana Carolina Silva d'Ornelas2, Angelica Jesus de Assis2, Camila Alves Quintino de Souza2, Samantha de Jesus Carolina2, Mariana Balbi Seixas1, Lilian Pinto da Silva1 (1) Graduate Program in Physical Education, Faculty of Physical Education and Sports, Federal University of Juiz de Fora, Juiz de Fora, Brazil; (2) Faculty of Physical Therapy, the Federal University of Juiz de Fora, Juiz de Fora, Brazil; (3) Graduate Program in Rehabilitation Sciences and Physical-Functional Performance Faculty of Physical Therapy, Federal University of Juiz de Fora, Juiz de Fora, Brazil Background: Although it is widely known that physical exercise contributes to blood glucose control and reduces cardiovascular risk factors, adopting and maintaining an aerobic exercise routine (AER) is still a challenge for people living with diabetes as it requires overcoming several barriers. Therefore, it becomes relevant to identify these barriers and correlate them with adherence to AER. Methods: Participants of a randomized pilot study involving a 12-week exercise intervention aiming to maintain an AER with at least 150 min/week in moderate-intensity were follow-up for six-month post-intervention. The follow-up objective was to support the participants in maintaining the AER through monthly structured phone calls; in the five calls, they answered a Likert scale about the impact of barriers on AER (No impact - 0 and extreme ) and reported minutes AER/week. The ten pre-established barriers are presented in Table 1. The participants were divided into two groups: G1) participants with AER >= 150min/week and G2) AER < 150min/week on average. The median for each barrier was calculated, and the Mann-Whitney test was used to compare the barriers between G1 and G2. The Spearman test analyzed the association between the interest variables. Results: During the six-month follow-up, 29 participants (55% male, 58.5 +- 9.0 yr, 10.3% prediabetes, 20.7% Type 1 diabetes, and 69% Type 2 diabetes) answered the phone calls. The average time of AER/week was 178 minutes, and 58% of participants reported AER >= 150 min/week during the follow-up. Table 1 shows the barriers comparing G1 and G2. Fatigue and lack of: company, space, and equipment had less impact on AER in the G1 than G2. A negative and moderate correlation was identified between fatigue, lack of time, lack of company, lack of space, and lack of equipment with the average time of AER/week (r = -0.50; -0.41; -048; -0.54; -0.55; P >= 0.05, respectively). Conclusion: Although some barriers were related to a short average time of AER/week, most participants could maintain more than 150 min/week of AER in moderate-intensity six months after a 12-week exercise intervention. 108759 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Diabetes Knowledge and Glycemic Control in Patients with Type 1 and 2 Diabetes ANA PAULA DELGADO BOMTEMPO BATALHA1, Josiane Aparecida de Almeida3, Juliana Gomes Soares2, Barbara Faria Filgueiras2, Isabela Coelho Ponciano3, Ana Carolina Silva d'Ornelas2, Angelica Jesus de Assis2, Camila Alves Quintino de Souza3, Samantha de Jesus Carolino2, Tamara Rafino de Castro2, Mariana Balbi Seixas1, Lilian Pinto da Silva1 (1) Graduate Program in Physical Education, Faculty of Physical Education and Sports, Federal University of Juiz de Fora, Juiz de Fora, Brazil; (2) Faculty of Physical Therapy, the Federal University of Juiz de Fora, Juiz de Fora, Brazil; (3) Graduate Program in Rehabilitation Sciences and Physical-Functional Performance Faculty of Physical Therapy, Federal University of Juiz de Fora, Juiz de Fora, Brazil Background: Some studies have shown that diabetes patients with higher disease knowledge are more likely to adhere to the treatment and achieve behavior change, which is critical for effective glycemic control. Therefore, this study aimed to compare diabetes knowledge between patients with type 1 (T1D) and type 2 diabetes (T2D) and investigate the correlation between this outcome and glycated hemoglobin (A1c) levels. Methods: Participants from different phases of the Diabetes College Brazil Study (NCT03914924) - (1) validation of questionnaires, n = 106; (2) pilot randomized trial, n = 18; (3) feasibility study, n = 7) - whose glycemic control has been assessed by A1c levels measured up to three months before been enrolled in one of the phases of Diabetes College Brazil Study were included in the present study. The diabetes knowledge was assessed by DiAbeTes Education Questionnaire (DATE-Q) total and each item scores. Mann-Whitney test was used to compare DATE-Q total scores between patients with T1D and T2D, and the Spearman test analyzed the association between DATE-Q total score and A1c level. Results: One-hundred and thirty-one diabetes patients (55 +- 14 yr; 59% female; 74% T2D; 48% with effective glycemic control (A1C < 7%); 23.6% elementary school non-concluded, 23.6% high school concluded and 17% postgraduate; average house income of 4 Brazilian minimum wages) participated in the study. The median and interquartile range of A1C level and DATE-Q total score were 7.2% [6.2-8.3] and 14 [12-16], respectively. Patients with T1D presented higher DATE-Q scores compared to those with T2D (total score: 16 [14-18] vs. 14 [11-15], P < 0.01; item scores: item 2, P = 0.01; item 3, P < 0.01; item 4, P = 0.03; and item 12, P = 0.03). There was no significant correlation between A1C levels and DATE-Q total scores as well as between A1C levels and DATE-Q each item scores. Conclusion: The result of higher diabetes knowledge in patients with T1D is predictable since it is recommended to provide at least some education as part of this disease's primary care. Although the non-association between DATE-Q scores and A1C levels found refutes our study hypothesis, it reinforces findings from other studies considering that diabetes control is related to disease type and treatment and psychosocial conditions rather than diabetes knowledge. 108807 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Antihypertensive Effect of New N-Acylhydrazones BRUNA DE SOUZA ROCHA1, Jaqueline Soares da Silva1, Julia Galvez Bulhoes Pedreira1, Eliezer Jesus Barreiro1, Gisele Zapata-Sudo1 (1) Universidade Federal do Rio de Janeiro (UFRJ) Introduction: Systemic arterial hypertension is a multifactorial condition with structural and/or functional changes in target organs, heart, brain, kidneys and vessels. The search of new strategies for the prevention and treatment of cardiovascular diseases, led to the design and synthesis of new N-acylhydrazones derivates, to identify agents with vasodilator activity and antihypertensive effect. New compounds containing selenium, which has antioxidant properties, which could provide reduction of the oxidative stress associated with hypertension. Objectives: To investigate the vascular and antihypertensive effects of new N-acylhydrazones. Methods: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro n. 017/19. Vascular reactivity was evaluated using isometric tension recording of pre-contracted thoracic aorta from male Wistar rats (220-250 g) after exposure to increasing concentrations of each derivate (0.1-100 mM) and was calculated the half maximal effective concentration (EC50). Two compounds (LASSBio-2062 and LASSBio-2063) were selected to investigate the antihypertensive effect in spontaneously hypertensive rats (SHR, 12-14 weeks old), through the measurement of mean blood pressure (MBP) and heart rate (HR) after intravenous administration of 10 mmol/kg. Results: The Table 1 shows EC50 of the compounds for the vasodilator effect in aorta in the presence and absence of endothelium. All derivates tested demonstrated vasodilator activity. LASSBio-2062 and its N-methylated analogue, named LASSBio-2063, were more potent than the prototype and LASSBio-2063-induced vasodilation occurs regardless of endothelium integrity. LASSBio-2062 and LASSBio-2063 (10 mmol/kg; n = 5, each) reduced MBP in SHR from 132.0 +- 9.2 to 82.1 +- 12.6 mmHg and from 129.7 +- 4.5 to 96.0 +- 14.6 mmHg, respectively (p < 0.05). LASSBio-2062 but not LASSBio-2063 reduced HR from 248.1 +- 12.1 to 146.5 +- 21.0 bpm. Conclusion: The vasodilator activity induced by the new N-acylhydrazones could explain their antihypertensive effect. 108809 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Short-Term Outcomes of Patients with Combined Systolic and Diastolic Heart Failure AHMAD GILL1, Omar Al-Taweel1, Dalia Hawwass1, Chowdhury Ahsan1 (1) University of Nevada, Las Vegas (UNLV) Introduction: There is limited research on patients with combined systolic and diastolic heart failure. Objective: In this study, we compare the short-term outcomes of patients with combined systolic and diastolic heart failure to patients with diastolic heart failure. Methods: This was a retrospective cohort study. We queried the National Inpatient Sample database from 2016 to 2018 and identified adult patients admitted with a principal diagnosis of combined systolic and diastolic heart failure or diastolic heart failure. We analyzed the categorical and continuous variables by Pearson's chi-squared and Student t-test respectively. Multivariable logistic regression, adjusted for age, gender and comorbidities, was used to compare mortality. The comorbidities adjusted for included coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, hypertension, obesity and type 2 diabetes mellitus. Results: 598,250 patients met our inclusion criteria. Patients with combined systolic and diastolic heart failure had 1.54 times higher odds of suffering in-hospital mortality compared to patients with only diastolic heart failure (aOR 1.54, 95% CI: 1.43-1.66; p < 0.001). When separated by race, combined heart failure patients had higher mortality rates amongst White (3.9% vs 2.7%, p < 0.001), Black (1.9% vs 1.6%, p < 0.001) and Hispanic (3.0% vs 1.8%, p < 0.001) patients. Patients with combined heart failure were predominantly male (57.6% vs 38.2%, p < 0.001), had longer hospital stays (5.8 days vs 5.1 days, p < 0.001) and increased hospital costs ($56,544.60 vs $41,666.02, p < 0.001). These patients also had higher rates of comorbidities such as coronary artery disease (46.2% vs 35.1%, p < 0.001) and prior myocardial infarction (12.9% vs 7.0%, p < 0.001), but decreased rates of hypertension (28.4% vs 33.2%, p < 0.001), obesity (16.5% vs 22.6%, p < 0.001) and type 2 diabetes mellitus (24.0% vs 26.2%, p < 0.001). Conclusion: Patients with combined systolic and diastolic heart failure had higher odds of suffering in-hospital mortality compared to patients with only diastolic heart failure. Our findings illustrate that combined heart failure patients require close monitoring in the inpatient setting. Additional studies should explore if specific races are at increased risk for prolonged hospitalization and mortality. 108813 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Is Home Blood Pressure Monitoring Useful in Diagnosing Hypertension in Young Adults in Primary Care? TAISSA LORENA DOS SANTOS1, Taissa Lorena dos Santos1, Tomas de Souza Mello1, Ana Rachel Buchar Cervasio1, Bruna Gopp Botelho1, Carlos Augusto Parente Macedo Moura1, Karine da Silva Guimaraes1, Ana Cristina Tenorio da Costa Fernandes1, Daniela Fiuza Gomes Monteiro1, Elizabeth Silaid Muxfeldt1 (1) Universidade Estacio de Sa, School of Medicine, Campus Vista Carioca. IDOMED Background: Recent guidelines have recommended out-of-office blood pressure (BP) measurement to improve the accuracy of the diagnosis of hypertension (HTN) but there are few studies evaluating its use in the younger population and in the scope of primary care. Objective: To assess the degree of agreement between office BP and HBPM, evaluating their use in a young population assisted in primary care. Methods: This is a cross-sectional population study with adults between 20-50 years old registered in the Family Health Strategy. Sociodemographic, anthropometric data and CV risk factors were recorded. Office BP was the mean of 2 measurements and HBPM followed the 7-day protocol. HBPM < 135 x 85 mmHg and office BP < 140 x 90 mmHg were considered normal, identifying the 4 phenotypes: Normotension (controlled office BP and HBPM); white-coat HTN (uncontrolled office BP and controlled HBPM); masked HTN (controlled office BP and uncontrolled HBPM) and sustained HTN (uncontrolled office BP and HBPM). Results: 475 individuals were included (male sex: 38%; mean age: 37.6 years +-8.8 years, of which 93 (20%) had their diagnosis modified after HBPM (43 with white-coat and 47 with masked HTN). In multiple logistics regression, male gender (OR 3.87: 95%CI 1.70-8.82) was independently correlated with white-coat HTN, while obesity and prehypertension increased the risk of masked HTN by 2 and 5.5 times, respectively. Uncontrolled office BP has high specificity (89%) and low sensitivity (49%) for detecting sustained HTN, with a low concordance in the diagnosis of HTN (kappa = 0.388) Among men with uncontrolled office BP, 55.6% had a diagnosis of white-coat HTN and among women, 37.1%. Conclusion: HBPM was a useful procedure in the diagnosis of hypertension in a young and apparently healthy population in primary care, especially in those with uncontrolled office BP to identify white-coat HTN and in those with high normal office BP, especially if they are male or obese for early diagnosis of masked HTN. 108820 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Changes in Clinical Profile of Refractory Hypertensives After the Introduction of Spironolactone TAISSA LORENA DOS SANTOS1, Taissa Lorena dos Santos1, Carlos Filipe dos Santos Pimenta1, Victor Margallo1, Hugo Farah Affonso Alves1, Lucca Hiroshi de Sa Kimura1, Joao Gabriel Rega do Nascimento Vallaperde1, Vitor de Melo Nolasco1, Joao Gabriell Bezerra da Silva1, Bernardo Chedier1, Elizabeth Silaid Muxfeldt1 (1) Universidade Federal do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho - ProHArt. UFRJ - HCUFF Introduction: Refractory hypertension (RfHTN) is defined as uncontrolled blood pressure despite the use of 5 or more anti-hypertensive drugs. It is considered the extreme phenotype of resistant hypertension (RHTN). Objectives: To characterize prevalence and clinical profile of patients with RfHTN among a historical cohort of patients with RHTN in 2 moments: before and after the introduction of spironolactone. Design and Methods: A cross-sectional analysis was performed during the pre-spironolactone period (before 2005) with 1,048 participants with RHTN (72.3% women, average age: 61.2 +- 11.3 years). All of them were submitted to a standard protocol including clinical and laboratory tests, 24-hour ABPM, echocardiogram, and pulse wave velocity. In a second analysis, refractory patients were evaluated after the introduction of spironolactone (post-spironolactone period - after 2005). The statistical analysis included bivariate comparisons between patients with RHTN and those with RfHTN, as well as logistic regressions to assess independent correlations of RfHTN post-spironolactone. Results: In the initial cross-sectional analysis (pre-spironolactone), RfHTN prevalence was 14%. Age < 60 years, smoking, obesity and left ventricular hypertrophy (LVH) were independently correlated with RfHTN. After the introduction of spironolactone, prevalence increased to 17.6%. It was observed that refractory patients using spironolactone presented less aortic stiffness, lower prevalence of LVH, cerebrovascular disease and peripheral arterial disease (PAD), what might indicate a reduced cardiovascular risk despite the lack of blood pressure control. Refractory patients have also presented higher magnitude of white-coat effect, reflecting an exacerbated sympathetic activity. Age < 60 years and lower prevalence of PAD were correlated with RfHTN in the post-spironolactone period. Conclusion: The use of spironolactone seems to reduce cardiovascular risk despite the lack of blood pressure control. 108831 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Consumption of Ultra-Processed Foods and Risk of Death from Noncommunicable and Cardiovascular Diseases: Elsa-Brasil Cohort FERNANDA MARCELINA SILVA1, Luana Giatti Goncalves1, Luisa Campos Caldeira Brant1, Maria de Fatima Haueisen Sander Diniz1, Alvaro Vigo2, Maria de Jesus Mendes da Fonseca3, Sandhi Maria Barreto1 (1) Universidade Federal de Minas Gerais, UFMG; (2) Universidade Federal do Rio Grande do Sul, UFRGS; (3) Escola Nacional de Saude Publica, ENSP/Fundacao Oswaldo Cruz, Fiocruz Introduction: Changes in dietary patterns related to food processing have been associated with an increase in the incidence of several noncommunicable diseases (NCDs). Greater consumption of ultra-processed foods (UPF) was associated with a higher risk of death from all causes and cardiovascular diseases (CVDs), but results are controversial, especially for CVDs mortality. Objectives: To investigate whether the consumption of UPF is associated with a higher risk of death from NCDs and CVDs in Brazilian adults after eight years of follow-up. Methods: A total of 14,011 adults from the baseline (2008-2010) of the ELSA-Brasil cohort study, aged between 35 to 74 years and free of CVDs were included. Food consumption at cohort insertion was obtained using a food frequency questionnaire and the NOVA classification was used to estimate the contribution of UPF, in grams/day, on the total dietary. The following baseline variables were used for adjustments: sex, age, investigation center, schooling, physical activity, smoking, excessive alcohol use, total energy intake, body mass index (BMI), and reported diagnosis of diabetes, hypertension, and use of lipid-lowering drugs. The association between UPF consumption and time to death from NCDs and CVDs was investigated using Cox regression models, after adjustments. Restricted cubic spline regressions were used to test nonlinearity. The participants were followed from the first year of the cohort until the date of death, lost to follow-up, or December 31, 2018, whichever came first. Results: After a mean follow-up of eight years, 331 deaths from NCDs and 116 from CVDs occurred. The proportion of UPF in the diet was 16.1% (10.5-23.4). After adjustments, the results suggested that a 10% increase in UPF consumption increased the risk of death from NCDs by 15% (95% CI: 1.03-1.29). These results were maintained even after adjustments for total energy intake and BMI and for comorbidities. However, no association was observed between UPF consumption and CVDs mortality. Conclusions: An increase in UPF consumption was associated with a higher risk of death from NCDs. These results support public policies aimed at reducing UPF consumption and encouraging the consumption of unprocessed foods for NCDs prevention. However, a longer follow-up period may be necessary to assess the association between UPF consumption and cardiovascular mortality. 109110 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Cardiovascular Changes in Pediatric Patients with COVID-19: A Systematic Review VICTOR LUIZ ROCHA PIRES1, Murilo Sousa Ramos1, Beatriz Rihs Matos Tavares1, Quelvin Claiton Souza Costa1, Grasiely Faccin Borges1 (1) Universidade Federal do Sul da Bahia (UFSB) Introduction: Children affected with COVID-19 are mostly asymptomatic, in this way, they do not belong a group of risk for this disease, due to mild symptoms, a better prognosis and low lethality. Recent studies describe that some children were affected with Multisystem Inflammatory Syndrome owing to COVID-19 and facilitated complications, such as mitral regurgitation, vasculitis, myocarditis, valve regurgitation, pericardial effusion, and electrocardiographic changes, thus increasing hospitalization and care intensive. Objective: To analyze the incidence of cardiovascular changes in pediatric patients associated with COVID-19. Methodology: This is a systematic literature review study, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Researches and studies were performed in SciELO, LILACS, PUBMED, MEDLINE and BVSalud. Original articles on cardiovascular changes in pediatric patients, whose ages ranged from 0-18 years old, with complications repercussions for COVID-19, in the period from 2020 to 2022, were included. Results: Of the 40 studies found, three were included, one research has pointed out that a third of pediatric patients who had COVID-19 had coronary changes; Kawasaki disease and the multisystem inflammatory response stand out, which occurred in most patients, followed by cardiogenic shock and other shocks. In the imaging tests, it was observed 53% had left ventricular dysfunction, 27% had right ventricular dysfunction, and the others evolved with low normal systolic function and pericardial effusion. Laboratory standards showed an increase in the mean level of partial thromboplastin time and C-reactive protein, as well as hydroelectrolytic repercussions, which were related to prognosis and mortality. Conclusion: There are a few studies that analyzed children affected by COVID-19, and these indicate the possibility of pediatric patients to develop serious cardiovascular complications after infection by SARS-CoV-2. 110853 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Vascular Responses to Mental Stress in Postmenopausal Women with Treatment-Resistant Hypertension: The Role of Nitric Oxide/Cgmp AMANDA SAMPAIO STORCH1, Helena Naly Miguens Rocha1, Joao Dario Mattos1, Larissa Lirio Velasco1, Juliana Mentzinger1, Gabriel Fernandes Teixeira1, Rebeca Lial Rosado1, Antonio Claudio Lucas da Nobrega1, Ronaldo Altenburg Odebrecht Curi Gismondi1, Natalia Galito Rocha Ayres1 (1) Fluminense Federal University Introduction: Patients with treatment-resistant hypertension (TRH) usually present mental stress (MS)-induced impairments in the endothelial dysfunction. We suggest that the decrease in nitric oxide (NO) bioavailability evoked by MS may aggravate vascular function in those patients. Objective: To determine the effects of increasing NO bioavailability during MS through inhibition of phosphodiesterase-5 on vascular response in those patients. Methods: It is a cross-sectional, randomized, crossover, double-blind, and placebo-controlled protocol (CAAE: 79958017.3.0000.5243). In two experimental sessions, postmenopausal women with TRH (61 +- 5 years) underwent a randomized oral administration of PDE-5 inhibitor (iPDE5; sildenafil 50 mg) or placebo (PL). After 30 minutes, the patients were submitted to MS (modified Stroop Color-Word Test) for five minutes. Flow-mediated dilatation (FMD; vascular ultrasound) and pulse wave analyses (applanation tonometry) were measured at baseline, immediately after (MS), and 30 minutes after MS (MS30). Blood samples were collected at baseline, during MS, and MS30 to measure coagulation (coagulometry), oxidative stress (colorimetry), and nitrite/nitrate concentration (chemiluminescence). Heart rate (HR; electrocardiogram) and BP (photoplethysmography) were continuously monitored throughout the protocol. Data were presented as mean +- standard deviation. Two-way repeated-measures ANOVA was used to compare baseline, MS, and MS30 measurements between sessions. Paired Student's T-test was performed to compare the delta values, followed by effect size Cohen's D test. Results: Preliminary results showed that MS increased the HR and systolic BP (p < 0.05) in both sessions. Baseline FMD was higher in the PL session (p = 0.02). However, there was a reduction in FMD at MS and MS30 in the PL session (p < 0.01 vs. baseline), while FMD was higher at MS30 in the iPDE5 session (p = 0.05 vs. baseline; p < 0.01 vs. PL). Additionally, the FMD response at MS30 was higher in iPDE5 compared to PL session with a medium effect size (p = 0.02; Cohen's D:0.64). Nitrate concentration was higher at baseline and during MS in the iPDE5 session (p = 0.05 vs. placebo). No differences were observed throughout the protocol or in the response at MS30 in pulse wave analysis, coagulation, oxidative stress, and nitrite measurements. Conclusions: Present data suggest that the PDE-5 inhibition attenuates the deleterious effects of MS on endothelial function in patients with TRH. 108864 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocardial Injury and Prognosis in Hospitalized Brazilian COVID-19 Patients: Results from the Brazilian COVID-19 Registry HANNAH CARDOSO BARBOSA1, Maria Auxiliadora Parreiras Martins1, Manuela Furtado Sacioto2, Jordana Cristina de Jesus3, Karina Cardoso Meira3, Luiz Guilherme Passaglia1, Milena Soriano Marcolino1, Carisi Anne Polanczyk4 (1) Universidade Federal de Minas Gerais UFMG; (2) Faculdade Ciencias Medicas de Minas Gerais FCMMG; (3) Universidade Federal do Rio Grande do Norte UFRN; (4) Institute for Health Technology Assessment (IATS/CNPq) Background: Cardiovascular complications of COVID-19 represent an important aspect of the disease's pathogenesis and prognosis. Troponin levels are commonly abnormal in hospitalized patients with COVID-19 and they are associated with poorer prognosis. Evidence on the prognostic role of troponin and myocardial injury in COVID-19 in-hospital patients from Latin America are still scarce. This study aimed to fill this gap by evaluating myocardial injury as an independent predictor of in-hospital mortality and mechanical ventilation requirement in COVID-19 hospitalized Brazilian patients. Methods: This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals in 17 cities. Consecutive patients admitted with confirmed diagnosis of COVID-19 between March and September 2020 were included. Medical records were reviewed to collect data regarding patients' demographic and clinical characteristics; COVID-19 symptoms; clinical assessment upon hospital presentation, third and fifth days of hospitalization; laboratory, imaging, and electrocardiographic data; in-hospital medications, treatment, and patient outcomes. Models for the primary outcomes were estimated by Poisson regression with robust variance. For the multivariate analyses, two predictive models were estimated to evaluate the role of elevated troponin on the primary outcomes: in-hospital mortality and mechanical ventilation requirement. Results: Overall, 2,925 patients were included in this analysis. The median age was 60 (IQR 48-71) years old. The proportion of patients with comorbidities was higher in the group of people with cardiac injury. Laboratory tests brain natriuretic peptide, creatine phosphokinase, lactate dehydrogenase, N-Terminal pro-brain natriuretic peptide and C-reactive protein presented higher median values in patients with myocardial injury and this condition was a significant independent predictor for risk death and mechanical ventilation requirement. Patients with myocardial injury represented by elevated troponin levels, presented a higher risk of death relative risk (2.03 [1.60-2.58]) and mechanical ventilation requirement relative risk (1.87 [1.57-2.23]) when compared to controls. Conclusion: Cardiac injury showed to be an independent predictor of in-hospital mortality and need of mechanical ventilation in hospitalized COVID-19 patients. The design of strategies involving the continuous monitoring of troponin levels as risk biomarkers in thes. 109466 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Real-World Comparison between Inspiron Sirolimus-Eluting Stent and Other Third-Generation Drug-Eluting Stents in Patients with ST-Elevation Myocardial Infarction Submitted to Primary Percutaneous Coronary Intervention (Instemi Registry) GUSTAVO NEVES DE ARAUJO3, Guilherme Pinheiro Machado1, Marcia Moura4, Anderson Donelli da Silveira1, Pedro A. Lemos5, Alexandre Schaan de Quadros4, Marco Vugman Wainstein2 (1) Hospital de Clinicas de Porto Alegre (HCPA); (2) Universidade Federal do Rio Grande do Sul (UFRGS); (3) Imperial Hospital de Caridade; (4) Instituto de Cardiologia do Rio Grande do Sul (IC-FUC); (5) Hospital Israelita Albert Einstein Introduction: Coronary drug-eluting stents are continuously developing, and the current gold standard consists of new metal alloys with thinner struts and bioresorbable polymers. Our aim was to compare a new ultrathin strut, sirolimus-eluting stent (Inspiron(r)) with other third-generation drug-eluting stent platforms in patients with ST-elevation Myocardial Infarction (STEMI) submitted to primary percutaneous coronary intervention (PCI). Methods: The present work assessed clinical outcomes from a STEMI multicenter registry, from two centers in southern Brazil. Patients were considered for inclusion if they were admitted with STEMI and were submitted to primary PCI. All patients included received third generation DES, and Inspiron(r) was compared with five other stent platforms. A propensity score matching (PSM) adjusted for age, diabetes, admission Killip classification, cardiac arrest and creatinine was computed to generate similar groups in relation to clinical and procedural characteristics. Results: From January 2017 to January 2021, 1711 patients have undergone primary PCI and 1417 patients matched our entry criteria (709 in the Inspiron and 708 in the other third generation DES). Rates of hypertension (60 vs. 65%, p = 0.042), chronic kidney disease (2.7 vs 6.6%, p < 0.001), admission cardiogenic shock (5.2 vs. 9.5, p = 0.002) and cardiac arrest (1.0 vs. 7.2, p < 0.001) were lower in Inspiron group. After PSM, the study sample was comprised of 706 patients (353 in the Inspiron and 353 in the other third generation). Differences in baseline characteristics described above have lost significance. The rates of new revascularization (OR 0.52, CI 0.21-1.34, p = 0.173), stent thrombosis (OR 1.00, CI 0.29-3.48, p = 1.000), new revascularization (2.0 vs. 3.7%, OR 0.52, CI 0.21-1.34, p = 0.173), mortality (HR 0.724, CI 0.41-1.27, p = 0.257) and MACE (OR 1.170, CI 0.77-1.77, p = 0.526) were similar between groups after a median follow up of 17 months. Conclusion: Our findings support that Inspiron is safe in patients with STEMI, with similar outcomes after propensity score adjustment compared to well stablished third generation drug-eluting stents in the treatment with primary PCI at a long-term follow-up. 108891 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Altered Neck Circumference as an Indicator of Cardiovascular Risk Among Hypertensive Patients Treated in Primary Health Care LUCAS CAUNETO SILVEIRA1, Patricia Pereira de Almeida2, Marselha Marques Barral1 (1) Hospital e Maternidade Therezinha de Jesus - HMTJ; (2) Universidade Federal de Juiz de Fora - UFJF Introduction: Excess body fat is a modifiable risk factor associated with chronic non-communicable diseases, including systemic arterial hypertension (SAH). Regarding the assessment of nutritional status, anthropometric measurements are inexpensive; among which the neck circumference (NC) has been used as an indicator of cardiometabolic risk, as it estimates the accumulation of fat in the upper segment of the body. In addition, NC is considered an accessible measurement, it does not change with food intake and can be measured without the need to remove clothes. Objectives: To identify the presence of altered neck circumference among hypertensive patients treated in primary health care. Methods: Cross-sectional study conducted from September 2019 to March 2020 with adults and elderly treated in primary health care in the municipality of Guidoval-MG. We collected socioeconomic, lifestyle, health history data through a questionnaire and took anthropometric measurements. We measured neck circumference with an inelastic tape; with the participant standing and the head in a straight position, the tape was positioned at the midpoint of neck height. For the classification of NC, we used the cutoff point proposed by Zanuncio et al (2017), which considers NC>39.5 cm for men and NC>33.3 for women associated with cardiometabolic risk. The diagnosis of SAH was self-reported and confirmed in the electronic medical record. The study was approved by the Research Ethics Committee of the Federal University of Vicosa, under protocol number 3,189,427. We analyzed data using descriptive statistics, with calculation of mean, standard deviation and prevalence. Results: The sample consisted of 361 individuals with a prevalence of systemic arterial hypertension of 40.2% (n = 145). Among hypertensive patients (n = 145), the mean age was 58 +- 12.6 years and 91 individuals (62.8%) were identified with altered neck circumference, the majority being female (n = 74). Thus, there was a high prevalence of hypertensive patients with altered neck circumference measurements. Conclusion: Our findings are in agreement with the literature, which states that NC constitutes an indicator of cardiometabolic risk and its alteration is associated with other chronic diseases such as SAH and diabetes. Therefore, due to its facility and low cost, NC measurement can be adopted in health services, especially in places where there is a scarcity of human and financial resources. 109084 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Complications Associated with Myocardial Injury in Patients with COVID-19 JOAO DARIO MARTINS DE MATTOS1, Joao Dario Mattos1, Eduardo Schaustz1, Andrea Silvestre de Sousa2, Emiliano Horacio Medei3, Denilson C. de Albuquerque1, Olga Ferreira de Souza1, Fernando A. Bozza1, Gabriel C Camargo1, Juliana Ferreira4, Ronir Raggio Luiz3, Renata J Moll-Bernardes1 (1) D'OR Institute Research & Education (IDOR); (2) National Institute Of Infectious Diseases (Oswaldo Cruz Foundation); (3) Federal University of Rio de Janeiro; (4) Hospital Copa D'OR Background: Myocardial injury (MI), detected by elevations in cardiac troponin is common in hospitalized patients with COVID-19, and has been associated with adverse outcomes and mortality; however, there is still some controversy regarding the role of this biomarker, and routine measurement of troponin levels to increase risk stratification is not recommended. Aim: To explore the association between MI with mortality and complications in hospitalized patients with COVID-19. Methods: Consecutive adult hospitalized patients with COVID-19 were included prospectively in a multicenter registry (n = 3246). Troponin levels were normalized to the 99th percentile upper reference limit (URL) and presented as ratios. Myocardial injury was defined by troponin >1 x URL. Troponin ratios were categorized as normal (<=1x URL), mildly elevated (>1 to <=3x URL), moderately (> 3 to <=10x URL) and severely elevated (>10x URL). Clinical data was collected from electronic medical records. Patients were prospectively followed until hospital discharge or in-hospital death. Results: Myocardial injury was associated with increased in-hospital mortality (22.7% vs 5.5%) and most cardiovascular adverse outcomes, such as thromboembolic phenomena (4.0% vs 2.6%; p = 0.047), myocarditis (4.8% vs 1.2%; p < 0.001), heart failure (6.5% vs 1.3%; p < 0.001), myocardial ischemia (9.1% vs 1.4%; p < 0.001), sepsis or septic shock (20.1 vs 9.2%; p < 0.001), acute renal failure (21.8% vs 7.4%; p < 0.001) and respiratory failure requiring mechanical ventilation (36.5% vs 10.8%; p < 0.001). From a total of 3246 patients in our cohort, 1770 (54.5%) did not have troponin measurement during the first week of hospitalization. In-hospital mortality was higher in patients with no troponin measurement compared to patients with no myocardial injury (11.9% [95%CI, 10.5-13.5] vs 5.5% [4.3-7.0]), highlighting the negative predictive value of this biomarker. Some complications were also more prevalent in patients with no troponin measurement, compared to patients with normal troponin levels. Conclusion: Our findings suggest that troponin is an important biomarker that may improve risk prediction and resource utilization in hospitalized patients with COVID-19. 108920 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Social Determinants of Outpatient Healthcare Utilization and Related Costs Among Patients with Rheumatic Heart Disease: A Longitudinal Study in Uganda XINPENG XU1, Jenifer Atala2, Andrea Z. Beaton3, Rosemary Kansiime2, Miriam Nakitto2, Emma Ndagire5, Haddy Nalubwama2, Emmy Okello5, Emily Chu6, Hui Miao7, David A. Watkins8, Yanfang Su8 (1) School of Public Health, Nanjing Medical University, Nanjing, China; (2) Department of RHD Research, Uganda Heart Institute, Kampala, Uganda; (3) Department of Cardiology, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; (4) Department of Pediatrics, School of Medicine, University of Cincinnati, Cincinnati, OH, United States; (5) Division of Cardiology, Uganda Heart Institute, Kampala, Uganda; (6) Interlake High School, Bellevue, WA, United States; (7) Vanke School of Public Health, Tsinghua University, Beijing, China; (8) Department of Global Health, University of Washington, Seattle, WA, United States; (9) Department of Medicine, University of Washington, Seattle, WA, United States Introduction: Rheumatic heart disease (RHD) is prevalent in socially disadvantaged settings, placing a severe burden on patients and their households. Many studies have highlighted the relationship between social determinants and RHD disease development, but there is limited understanding about social determinants of healthcare utilization and related financial and time costs among RHD patients. Objective: To investigate social determinants of healthcare utilization and related costs among RHD patients in Uganda. Methods: This was a retrospective longitudinal study involving patients with RHD recruited from the Uganda National RHD Registry. Our survey included 87 patients from the registry stratified by 3 districts in Uganda. Between December 2018 and February 2021, data were collected. A random-effects model was used to examine the associations between social determinants and healthcare utilization, as well as financial and time costs. Results: Among the social determinants, increase of an additional person per bedroom is associated with the reduction of outpatient spending by 1.73 USD per visit (P < 0.05), owing primarily to a reduction in direct medical spending (1.25 USD; P < 0.01). RHD patients under the age of 18 had 3.2 more outpatient visits annually (P < 0.01), and their per-visit time costs and those of caregivers were 2.5 hours (P < 0.05) and 4.9 hours (P < 0.05) more than those of adult RHD patients, respectively. More educated individuals spend 2.5 USD less on nonmedical cost per visit (P < 0.05). In Western Region, which is underdeveloped in Uganda, the number of annual outpatient visits by patients with RHD were 4.8 higher than those in the Central Region(P < 0.01); RHD patients living in western region faced 3.8 USD higher direct medical costs per outpatient visit (P < 0.1) and more missed work hours (1.9 hours, P < 0.1). Conclusions: RHD patients underutilized RHD secondary prevention and experienced high healthcare expenditures. Crowding, age, and geographical characteristics all have significant correlation with RHD patients' healthcare utilization and costs. Targeted measures, such as expanding housing construction and improving housing maintenance, reducing barriers in RHD secondary prevention among adult patients, ensuring the supply of medicines in economically worse-off areas, should be taken to ensure that equitable and affordable medical services are available to those RHD patients who are most in need of secondary prevention services. 108924 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Impact of Systemic Lupus Erythematosus in Patients with Hypertrophic Obstructive Cardiomyopathy AHMAD GILL1, Emily He2, Omar Al-Taweel1, Dalia Hawwass1, Chowdhury Ahsan1 (1) University of Nevada, Las Vegas (UNLV); (2) Loma Linda University (LLU) Introduction: Although there is extensive literature present on hypertrophic obstructive cardiomyopathy (HCOM), there is limited data on HCOM patients with systemic lupus erythematosus. Objective: In this study, we investigate the short-term, in-hospital outcomes of HCOM patients with and without systemic lupus erythematosus. Methods: We queried the National Inpatient Sample database from 2016 to 2018 to identify adult patients admitted with a principal diagnosis of HCOM and a secondary diagnosis of systemic lupus erythematosus. We analyzed the categorical and continuous variables by Pearson's chi-squared and Student t-test respectively. Multivariable logistic regression, adjusted for age, gender, comorbidities, hospital bed size, hospital region and hospital teaching status was used to compare mortality. The comorbidities adjusted for included atrial fibrillation, coronary artery disease, chronic kidney disease, heart failure, hypertension, obesity and type 2 diabetes mellitus. Results: 9395 patients met our inclusion criteria, of which 35 patients had both HCOM and systemic lupus erythematosus. Patients with HCOM and systemic lupus erythematosus had 7.08 times higher odds of suffering in-hospital mortality compared to patients with solely HCOM (aOR 7.08, 95% CI: 1.21-41.32; p = 0.03). When separated by race, HCOM and systemic lupus erythematosus patients had a higher mortality rate in White patients (21.7% vs 1.6%, p < 0.001), but decreased mortality rates in Black (0% vs 2.9%, p = 0.67) and Hispanic (0% vs 2.0%, p = 0.73) patients. Patients with both HCOM and SLE were predominantly female (85.7% vs 58.6%, p = 0.15) and had lower median household income (71.4% vs 23.6%, p = 0.02). These patients also had higher rates of comorbidities such as coronary artery disease (42.9% vs 28.0%, p = 0.05), chronic kidney disease (14.3% vs 0.8%, p < 0.001), chronic obstructive pulmonary disease (42.9% vs 9.8%, p < 0.001) and prior myocardial infarction (14.3% vs 5.0%, p = 0.01), but decreased rates of atrial fibrillation (0% vs 28.1%, p < 0.001), heart failure (14.3% vs 28.4%, p = 0.06) and hypertension (28.6% vs 42.8%, p = 0.09). Conclusion: Patients with HCOM and systemic lupus erythematosus had higher odds of suffering in-hospital mortality compared to patients with solely HCOM. Our findings illustrate that patients with HCOM and systemic lupus erythematosus are a vulnerable population that require additional medical support in the acute care setting. 108930 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Increased Myocardial Retention of Mesenchymal Stem Cells and Improved Cardiac Function Post-MI by Pre-Conditioning Exercise Training STELLA DE SOUZA VIEIRA1, Brunno Lemes de Melo1, Ednei Luiz Antonio1, Fabio Navarro Marques2, Daniele de Paula Faria2, Paulo Jose Ferreira Tucci1, Andrey Jorge Serra1 (1) Laboratorio de fisiologia e fisiopatologia cardiacas. Universidade Federal de Sao Paulo (UNIFESP); (2) Instituto de radiologia, Hospital das clinicas da FMUSP, Universidade de Sao Paulo Introduction: Stem cell (SC) therapy is a promising approach to improve post-myocardial infarction (MI) cardiac remodeling, but the proinflammatory microenvironment may lead to SC loss and, therefore, may have a negative impact on therapy. It appears that exercise training (ET) improves myocardial microenvironment for SC transplantation. Objective: We tested the effect of ET on post-MI retention of adipose-derived SC and its combined effects on the inflammatory microenvironment. Methods: Female Fisher-344 rats (12 weeks) were randomized: SHAM; MI (MI); MI with SC (sMI); MI with ET and SC (esMI). Rats were trained 9 weeks prior to MI, followed by SC transplantation. Results MI led to left ventricular (LV) dilation and dysfunction; myocardial hypertrophy and fibrosis and increased expression of pro-inflammatory genes compared to SHAM rats. On the other hand, SC rats (sIM and esIM) exhibited better LV morphology and function; inhibition of hypertrophy and fibrosis; and attenuation of pro-inflammatory cytokines in the myocardium compared to MI rats. A positive correlation is observed between the expression of cytokines (interleukins 1b and 10, tumor necrosis factor a, and transforming growth factor b) and retention of SC. There was a correlation between cytokine expression and myocardial ADSCs retention. The. ET enhanced the beneficial effects of ADSCs in infarcted myocardium, which was associated with higher ADSCs retention. Conclusion: ET enhanced the beneficial effects of SC post-MI, which was associated with higher SC retention. Cytokine analysis suggests improvement in ET-linked myocardial microenvironment based on its anti-inflammatory action. 108953 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Personalized External Aortic Root Support (PEARS): First Cases in America IURI SCHWAAB1, Felipe Borsu de Salles2, Lucas Krieger Martins1, Rafael de Oliveira Ceron1, Marisa Fatima dos Santos1, Diogo Ferrari Centenaro1, Ari Tadeu Lirio dos Santos1, Joao Carlos Vieira da Costa Guaragna2, Renato Abdala Karam Kalil3 (1) Instituto de Cardiologia de Porto Alegre; (2) Hospital Divina Providencia; (3) Hospital Hospital Moinhos de Vento Aortic Root replacement is the standard treatment for Aneurysm in Marfan syndrome, despite the morbidity of this kind of surgery. Personalized External Aortic Root Support (PEARS) is a novel approach for this condition, which consists in applying an pre-tailored external prosthesis. Initial reports demonstrate low in-hospital morbidity and good mid-term aortic-specific complication prevention.1 We present the first three cases of PEARS in America. Patients were 2 male and 1 female, aged 30-41 years, with previous Marfan syndrome diagnosis and Aortic Root Aneurysm (ranging 47-52 mm). All patients had normal ventricular and kidney function, with no other systemic disease. All patients received standard aenesthesic monitorization and median sternotomy. Case #1 was submitted to PEARS and mitral valve repair (quadrangular resection and complete ring annuloplasty). He is a 33 years old male patient, with 52 mm aortic root aneurysm, mild aortic valve regurgitation and severe mitral regurgitation. Postoperatively Aortic Root size reduced to 42 mm, valvar function improved to only trace aortic and mitral valve regurgitation. Other 2 cases were submitted to PEARS off pump and were extubated in the operating room after the procedure. Case #2 is 41 years old, male, with 48 mm aortic root diameter and mild aortic valve regurgitation. After surgery aortic size was reduced to 43 mm and had complete correction of aortic regurgitation. Case #3 is 30 years old, female, with 47 mm aortic root diameter and trace of aortic valve function. Postoperative echo-cardiogram demonstrated reduction in aortic root aneurysm to 43 mm and stable valvar function. There was no surgical adverse event nor in-hospital clinical complication. Patients didn't require vasoactive drugs nor had significant postoperative bleeding or laboratory abnormalities. Intensive care unit stay was 2-3 days and in-hospital stay was 4-8 days. Postoperative echo-cardiogram demonstrated normal ventricular function, general reduction in aortic diameter and improvement of valvar function. PEARS demonstrate feasibility and safety in this initial surgical series. Long-term results may support the inclusion of PEARS as a therapeutic alternative for patients with Marfan syndrome and aortic aneurysm. REF: Van Hoof L, Rega F, Golesworthy T, et al. Personalised external aortic root support for elective treatment of aortic root dilation in 200 patients. Heart 2021; 107: 1790-1795. 108962 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Activation of Adenosine Receptor Reduces Inflammatory Process and Cardiac Remodeling Induced by Myocardial Infarction BIANCA DOS SANTOS CARLOS NASCIMENTO1, Jaqueline Soares da Silva1, Bruna Rocha1, Tadeu Lima Montagnoli1, Eliezer de Jesus Lacerda Barreiro1, Rodolfo do Couto Maia1, Gizele Zapata-Sudo1 (1) Universidade Federal do Rio de Janeiro - UFRJ Introduction: Treatment of acute myocardial infarction (AMI) is based on strategies to relief pain and increase survival. This work investigates the effects of a new agonist of adenosine receptor (AR) named LASSBio-1860, in experimental AMI, in order to improve cardiac function. Methods: Protocols were approved by the Ethics Committee for the Use of Animals at Universidade Federal do Rio de Janeiro (ndeg103/17). Experimental AMI was induced by ligation of the anterior descending coronary artery in male Wistar rats (180-200 g) which were randomly treated orally with either vehicle (DMSO) or 70 mmol/kg of LASSBio-1860. After 7 days of treatment, hemodynamic parameters were measured by catheterization and hearts were collected for evaluation of cardiac inflammation (TNF-alpha, p38 MAPK and iNOS) and remodeling (ERK-1/2 phosphorylated) markers using Western blot and immunohistochemistry analysis. Results: Left ventricle thickness was increased after AMI from 0.11 +- 0.04 to 0.29 +- 0.02 cm (p < 0.05) and reduced to 0.21 +- 0.01 cm after treatment with LASSBio-1860. AMI impaired ejection fraction to 45.2 +- 1.3% (Sham: 91.5 +- 0.5%, p < 0.05) which was partially reversed to 60.1 +- 10.3% after treatment. The agonist of AR normalized the increased filling pressure of AMI animals from 31.3 +- 6.3 (Sham: 18.6 +- 3.7) to 15.9 +- 3.9. Increased LV end systolic pressure was detected after AMI, changing from 83.8 +- 12.5 (Sham) to 104.7 +- 1.1 mmHg, and was recovered to 95.3 +- 21.4 mmHg by LASBio-1860. Elevated collagen deposition from 3.6 +- 0.9 to 31.5 +- 4.29% was observed in AMI hearts, which the treatment attenuated to 26.8 +- 1.6%. AMI increased the ratio of phosphorylated-to-total ERK-1/2 from 0.78 +- 0.01 to 0.89 +- 0.01 while LASSBio-1860 reduced to 0.79 +- 0.01 (p < 0.05). Similarly, cardiac content of p38 increased to 1.58 +- 0.36 after AMI but reduced to 1.17 +- 0.43 after LASSBio-1860. AMI also promoted increased p38 nuclear labeling from 9.9 +- 3.9 to 40.8 +- 3.3%, which was decreased to 29.9 +- 1.7 after treatment. Expression of iNOS increased in AMI from 9.0 +- 4.1 to 25.3 +- 3.9 and LASSBio-1860 improved to 14.2 +- 0.6%. Conclusion: Activation of AR by LASSBio-1860 led to improvement in AMI-induced cardiac remodeling and cardiac function. 109017 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Analysis of Epidemiological Indicators of Syphilis in Brazil between 2010 and 2021 and its Cardiovascular Implications PEDRO TOSCANO PAFFER1, Vitoria Maria Terra Lopes1, Camila Santiago de Castro1, Kamille Didier Melo Almeida1, Silvio Hock de Paffer Filho1 (1) Faculdade de Medicina de Olinda (FMO) Introduction: Despite the number of syphilis cases has decreased in recent years due to the advent of antibiotics and public policies for the prevention of Sexually Transmitted Diseases, cases of cardiac syphilis are still reported worldwide, especially in developing countries. The cardiac sequelae of syphilis appears approximately 10 to 20 years after the initial infection. Understanding the relation between syphilis and its cardiovascular repercussions, its important to analyze the epidemiological indicators of syphilis in Brazil and its potential risk, with a view to preventing these complications. Objective: Analyze the epidemiological indicators of syphilis in Brazil and its potential risk of cardiovascular complications Methods Epidemiological, descriptive study with data obtained by SINAN (Information System on Notifiable Diseases). The platform was used to search for cases of acquired syphilis between 2010-2021, specifying by region, age group and gender. Results: Between 2010 and 2021, 911179 cases were reported in Brazil. The majority of the cases were reported in the South-east region, with 471767 cases (51%); followed by the South region, 203969 (22%); North-east region 121524 cases (13%); Mid-west region 63057 (6%) and northern region 50862 (5%). 549201 patients were male (60%). The age group with the highest incidence was between 20-39 years old, with 518970 cases reported (56.96%). Among people aged 60 years or older, 75368 cases (8.27%) were reported. In the year 2021 alone, 64279 cases were reported Discussion A total of 911179 cases of acquired syphilis were reported between 2010 and 2021, with its peak in 2018. Males had the highest incidence, with 549201. Syphilis infection has been linked to certain behavioral and social factors, including incarceration, multiple or anonymous sexual partners, sexual activity related to illicit drug use, and other high-risk sexual network dynamics. Given this large increase in the number of cases, there is a risk that in the future cases of cardiovascular involvement will increase. The most significant cardiovascular complication of cardiovascular syphilis is syphilitic aortitis, which leads to aortic aneurysm formation in most cases, and aortic valve insufficiency and coronary ostial stenosis in a minority of patients. Conclusion: The high incidency and cardiovascular implications the diseases carries, requires prevention, monitoring and adequate treatment, with awareness policies for the risk groups 109033 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Descriptive Analysis of the Correlation between the Prenatal and the Occurrence of Anomalies in the Cardiovascular System in the Period of 20 Years RENATA PINHEIRO MARTINS DE MELO1, Isabela Aragao Colares1, Mariana Salles Ballalai1, Jose Levi Tavares Cavalcante1, Gabriel Sousa Santos1, Helena Raquel Nogueira de Oliveira1, Marcelo Brito Cavalcante1, Gabriel Coelho Brito Dias1, Weiber Silva Xavier1, Sandra Nivea dos Reis Saraiva Falcao1, Joao Luiz de Alencar Araripe Falcao1 (1) Universidade Federal do Ceara (UFC) Introduction: Congenital anomalies are the fourth leading cause of neonatal death and, according to the World Health Organization (WHO), the most common and serious congenital disorders are heart problems, neural tube defects, and chromosomal abnormalities. In this sense, despite all advances in obstetrics and improvements in prenatal care for pregnant women, the prevention of mortality in neonates due to defects in the circulatory system remains a challenge to be overcome. Objective: Analyze, during the period from 1999 to 2019, the proper performance of prenatal care, correlated to the occurrence of deaths from cardiovascular defects in neonates. Methodology: Descriptive analysis, obtained from the DATASUS platform, of the frequency of prenatal care, the frequency of births with congenital anomalies and how many of these disorders are related to defects in the cardiovascular system and mortality rate in children under 1 year old due to diseases of the circulatory system. Results: During the period from 1999 to 2019, in Brazil, 8702 neonates died due to defects in the circulatory system and 3,443,087 women did not perform prenatal care or did it inappropriately. In addition, 30,734 children, whose mother didn't perform prenatal care or it was performed inappropriately, were born with a certain congenital anomaly, which represents 21% more than those who had congenital disorders, but prenatal care was being performed. Furthermore, of a total of 170,392 cases of births with anomalies, 17.3% were characterized by defects in the cardiovascular system. Conclusion: From the information above-mentioned, it is possible to correlate the inadequate performance of medical attendance during pregnancy and the occurrence of congenital defects, such as disorders in the circulatory system, because, with the performance of prenatal, the pregnant woman can be treated for a certain pathologies, such as hypertension and diabetes, to avoid harmful consequences to the fetus and to prevent the occurrence of premature birth, since premature neonates are twice as likely to have heart abnormalities. In addition, in case the fetus is already with the disturb, the prenatal allows to early diagnosis and treat the condition, increasing the survival percentage. In resume, performing prenatal care correctly, is essential for the prevention or the successful treatment of defects in the circulatory system in neonates and for the reduction of mortality in children under 1 year old. 109057 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Diagnostic Value of Cardiovascular Magnetic Resonance in Acute Peripartum Cardiomyopathy (PPCM) JULIAN HOEVELMANN1, Charle Andre Viljoen3, Stephen Jermy4, Jacqui Cirota5, Sarah Kraus5, Karen Sliwa2, Ntobeko AB Ntusi4 (1) Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Homburg (Saar), Germany; (2) Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; (3) Division of Cardiology, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; (4) Cape Universities Body Imaging Centre, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; (5) Department of Medicine, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Introduction: Peripartum cardiomyopathy (PPCM) is characterised by left ventricular (LV) dilatation and systolic dysfunction developing towards the end of pregnancy or in the first five months postpartum. Cardiovascular magnetic resonance (CMR) allows for comprehensive evaluation of myocardial structure, function, and tissue characteristics. There is a dearth of studies investigating utility of CMR in PPCM. Purpose: To evaluate diagnostic benefit of multiparametric assessment of myocardial oedema, fibrotic burden, and strain impairment in PPCM using CMR. Methods: Eighteen consenting women with newly diagnosed PPCM and 20 female, age-matched healthy controls (HCs) underwent CMR imaging on a 3T MR scanner. A comprehensive, contrast-enhanced CMR protocol was used. Images were evaluated qualitatively and semi-quantitively for the presence of late gadolinium enhancement (LGE). Results: Patients with PPCM (median age of 34.5 years [IQR 25-38]) presented with severely impaired LV ejection fraction (LVEF) of 31.4% (IQR 19.6-37.9) and reduced right ventricular (RV) ejection fraction (RVEF) of 37.2% (IQR 21.6-51.7). LGE was present in 13 (81.2%) PPCM patients and included linear or circumferential mid-wall, patchy and diffuse patterns (LGE mass 19.1g [IQR 15.0-26.5] vs. 11.4g [8.8-13.2] in HCs, p < 0.001). Patients with PPCM had significantly higher T1 times (1369.3 ms [IQR 1343.7-1409.7 vs. 1207.8 ms [IQR 1194.8-1241.3], p < 0.001) and ECV (36.5% [32.7-37.0] vs. 27.5 [26.3-28.5], p < 0.001) compared to HCs. RV dysfunction (present in 61.1% of PPCM cohort) was associated with significantly higher ECV (37.0% [IQR 36.5-38.4] vs 33.4% [IQR 28.5-37.0], p = 0.05 and higher T1 (1409.0 ms [IQR 1349.0-1443.0] vs. 1311.3 ms [IQR 1299.3-1369.3], p = 0.015) compared to those with preserved RV function. LV fibrosis was not significantly different between PPCM patients with and without RV dysfunction. LGE mass correlated negatively with LVEF and RVEF (r = -0.540, p = 0.001; r = -0.568, p < 0.001), respectively. There was a strong positive correlation between LGE mass and native T1 (r = 0.619, p < 0.001), LGE mass and GLS (r = 0.638, p < 0.001) and moderate correlation with ECV (r = 0.528, p = 0.001). Conclusion: For the first time, we report a high prevalence of myocardial fibrosis in well-phenotyped patients with newly diagnosed PPCM. Increased LGE mass was associated with severe impairments in LV strain, LVEF and RVEF. RV dysfunction was associated with significantly higher ECV and native T1 times. 109059 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Global Prevalence of Mortality and LV Recovery in Women with Peripartum Cardiomyopathy - A Systematic Review and Meta-Analysis JULIAN HOEVELMANN1, Mark E Engel3, Elani Muller2, Ameer Hohlfeld4, Michael Bohm1, Karen, Sliwa2, Charle Andre Viljoen5 (1) Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Homburg (Saar), Germany; (2) Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; (3) Department of Medicine, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; (4) South African Medical Research Council, Cape Town, South Africa.; (5) Division of Cardiology, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Introduction: Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications mainly occurring early during its course. Reported adverse outcomes include decompensated heart failure (HF), thromboembolic complications, arrhythmias and death. Purpose: We aimed to systematically summarize the outcomes of women with PPCM across different geographical regions. Methods: We performed a comprehensive search of all articles published between January 2000 and June 2021 on a number of electronic databases. All cohort, case-control and cross-sectional studies, as well as control arms of RCTs reporting on the in-hospital complications and /or 12-month outcomes of PPCM were considered eligible. Results: Forty-seven studies (4875 participants across 60 countries) met the eligibility criteria. Hemodynamic and echocardiographic parameters were similar across all continents. In-hospital mortality was reported as 1.9% [95% CI 0.5-4.0] across all regions. About 10% of patients received invasive ventilation, 21.5% inotropic and 3.1% received mechanical support, respectively. Left ventricular (LV) thrombus complicated 9.0% [95% CI 6.5-11.9] of patients and all-cause embolic events occurred in 6.1% [95% CI 3.8-8.9]. All-cause mortality was 8.0% [95% CI 5.5-10.8, I2 = 79,1%) at 6 months and 9.8% [95% CI 6.2-14.0], I2 = 80.48%) at 12 months respectively. Overall, 44.4% ([95% CI 36.2-52.8], I2 = 91.7%) of patients recovered their LV function within 6 months and 58.7% ([95% CI 48.1-68.9], I2 = 75.8%) within 12 months, respectively. The lowest rate of LV recovery was reported by studies conducted in the Middle East (13.6% [95% CI 9.5-18.1], 3 studies), whereas the highest rate of LV recovery was reported for patients from Europe (56.8% [95% CI 38.1-74.7], 6 studies, I2 = 93.3%). All-cause mortality was highest in Africa and Asia/Pacific. Europe and North America reported the highest prevalence of LV recovery. Frequent prescription of beta-blockers, ACE-I/ARB and bromocriptine treatment was associated with significantly lower all-cause mortality and better LV recovery. Conclusion: We identified significant global differences in prescribed treatment, prevalence of in-hospital complications and 12-month outcomes. Frequent prescription of guideline-directed HF therapy was associated with better outcomes. Timely initiation and up-titration of HF therapy should be strongly encouraged. 109066 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Cost of Managing Stroke in a Prospective Observational Cohort of 50 Acutely Hospitalized Cases in Maputo Mozambique IGOR SAMUEL DOBE1, Neide Canana1, Simon Stewart4, Ana Olga Mocumbi2 (1) Instituto Nacional de Saude; (2) Hospital Geral de Mavalane; (3) Universidade Edurdo Mondlane; (4) Torrens University Australia, Australia Introduction: Stroke is an often-deadly condition responsible for substantive great physical, social and economic limitations for survivors and their family globally. In LMIC, Unfortunately, there is a paucity of data describing its economic impact in sub-Saharan Africa. Our study aimed to evaluate the cost of stroke-related management and care during and post-hospitalization in Mozambique. Methods: We performed a prospective, cost-of-illness study (from the provider and patient perspective) of acute presentations of stroke to a first referral urban public hospital in Maputo, Mozambique. From June to December of 2019, 50 consecutively admitted patients were enrolled, data were collected from medical files and through interviews to patients or caregiver using semiquantitative questioner during hospitalization and by home visits in 28-days after discharge. Applying a bottom-up approach, direct and indirect costs were calculated. Data were presented as median, interquartile intervals, except financial data presented also as medians and ranges. All available costs were computed for the year 2019, the year of analysis. Results and discussion: In total 80 patients with acute stroke were admitted to ward during the study, of those, we consecutively recruited 50 patients comprised by 28 women (56%), a median age of 60.5 (38.3; 68.4) years, of whom 22 (44%) were discharged with diagnostic of hemorrhagic stroke. Median hospital stay was 7.0 (4.0; 8.0) days. 10 (20%) patients died within 28-days after discharge. Direct cost (Hospital stay, Medication, laboratory tests), for all cases was US$ 35 302,52 and the average direct cost per patient was US$ 706.05. Indirect cost (travel to hospital, family visits) during hospitalization and within 28-days post-discharge was US$ 22.00 and US$35,58, respectively, loss of productivity was very high in the informal sector, quality of life in all five dimensions were seriously compromised. The cost of stroke in Mozambique is particularly high considering, the relatively young age of affected cases. Conclusion: This study highlights the importance of understanding the costs of stroke for the system and for the patient. Routine register-based data can be used for accurate productivity cost estimates of health shocks. 109098 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSIOTHERAPY Predictors for Indication of Non-Invasive Ventilation in the Postoperative Heart Surgery in Adults JESSICA GONCALVES DE LIMA1, Victoria Maria Garcia de Medeiros1, Fernando Gomes de Jesus1, Ana Gabriella Arena de Sa1, Thaisa Sarmento dos Santos1, Mariana de Oliveira Carvalho1, Lucas Araujo de Carvalho1, Marcus Vinicius de Souza Amaral1, Juliana Rega1, Claudia Rosa1, Mauro Felippe Felix Mediano1, Luiz Fernando Rodrigues Junior1 (1) National Institute of Cardiology Introduction: Non-invasive ventilation (NIV) has been used for prophylaxis/treatment of pulmonary/respiratory complications during postoperative period (PO) of cardiovascular surgery. However, the indiscriminate use of prophylactic NIV may burden health systems due to the exacerbated use of human and material resources, resulting in a worsening of the standard of care provided. Objective: To identify the predictors for NIV indication in patients in the postoperative period of cardiovascular surgery. Methods: This was a retrospective cross-sectional study. Data from 614 patients submitted to cardiovascular surgery at the Instituto Nacional de Cardiologia (Rio de Janeiro-RJ), from October/2018 to March/2020, was obtained from the Physiotherapy Service database, stored on the Research Electronic Data Capture platform (REDCap) and complemented based on the review of physical records. Preoperative variables such as demographic data, comorbidities, functional class, cardiac function and risk assessment for cardiac surgery were collected. Intraoperative variables were: type/complexity of surgery, fluid balance, time on cardiopulmonary bypass (tCPB), time of aortic clamping and surgical complications. Variables evaluated in the PO were: level of consciousness, pain, water balance, imaging, laboratory and blood gas tests, tracheobronchial secretion, mechanics and pulmonary/respiratory function before and after extubation, extubation attempts and failures, and use of NIV after extubation. The univariate and multivariate logistic regression model (P < 0.05 considered significant) was used to verify the association of possible predictors with the NIV indication in the postoperative period of cardiovascular surgery. Results: The preoperative: age (OR:1.05; P = 0.005); the intraoperative: tCBP (OR:1.01; P = 0.046); and the postoperative variable: partial pressure of carbon dioxide (PCO2) before extubation (OR:1.08; P = 0.045) were independently associated with the need for NIV in the postoperative period of cardiovascular surgery. Conclusion: Age, tCPB and pre-extubation PCO2 are independent predictors of NIV need in patients in the postoperative period of cardiovascular surgery, so that the higher age, tCBP or PCO2, the greater the chances for the patient needing NIV, a finding that may encourage the choice of patients eligible for early intervention with NIV, and the creation of a score/calculator for supporting bedside decision about the use of prophylactic NIV. 109101 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Protocol for the Safety of Dobutamine Stress Echocardiography in a Large Unselected Population ISADORA SUCUPIRA MACHADO1, Tereza Cristina Pinheiro Diogenes1, Marilia Esther Benevides de Abreu2, Ana Gardenia Liberato Ponte Farias2, Marcia Maria Carneiro2, Jose Sebastiao de Abreu1 (1) Clinicardio Metodos Diagnosticos; (2) Cardioexata de Fortaleza Background: Adverse effects and serious complications can occur during dobutamine stress echocardiography (DSE) in a conventional protocol (CP). Objective: To assess the safety of DSE using a modified protocol (MP). Methods: Prospective collection of data from patients undergoing DSE, administering dobutamine in up to four stage. Atropine could be administered from the fourth stage in the CP and, as a routine, concomitant with the beginning of the third stage in the MP. At the end of the exam or to control arrhythmia, metoprolol was administered to the CP and esmolol to the MP. In the event of typical angina, the examiner defined the therapy in the CP, while in the MP, if necessary, a nitroglycerin solution could be infused over a period of three to twelve minutes. A p-value <0.05 was considered statistically significant. Results: Among 17,811 DSEs, 9,121 were included in the MP. Hypertensive peak (1% vs 0.4%; p = 0.0001) and non-sustained ventricular tachycardia (0.6% vs 0.1%; p = 0.0001) were more frequent in CP, while supraventricular tachyarrhythmia (1.9% vs 3%; p = 0.0001) and atrial fibrillation (0.8% vs 1.3%; p = 0.003) in the MP. These arrhythmias reversed spontaneously or with medication. Nitroglycerin was administered in 76 MP cases. Ventricular fibrillation and acute coronary syndrome occurred in CP. There was no acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, cardiac rupture, asystole, or death with MP. Conclusion: The MP for the DSE is a safe option in the application of this methodology. 109102 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Chronic Rheumatic Heart Disease Among Children and Adolescents in Brazil: Study of the Epidemiological Profile of Hospitalizations between 2010 and 2020 MATHEUS AKIRA SUZUKI DE OLIVEIRA1, Matheus Akira Suzuki de Oliveira1, Julia de Avila Gutierrez3, Karen Tassia Facanha Ramos2, Luiz Felipe Facanha Ramos2, Leo Christyan Alves de Lima4, Laura Jane Franca Lacerda4, Hildeman Dias da Costa1, Mathews Barbosa Santiago5, Ayrison de Melo Sousa5 (1) Universidade Federal de Rondonia; (2) Universidade Federal do Amapa; (3) Faculdades Integradas Aparicio Carvalho; (4) Centro Universitario Sao Lucas; (5) Centro Universitario Uninorte Introduction: Rheumatic heart disease is caused by damage to the heart valves and muscles that arise from inflammation and scarring caused by rheumatic fever. Rheumatic fever mainly affects children in developing countries, especially where poverty is widespread. About 2% of deaths from cardiovascular diseases in the world are related to rheumatic heart disease. Objective: To describe the epidemiological profile of hospitalizations for chronic rheumatic heart disease among children and adolescents in Brazil between 2010 and 2020. Methods: Cross-sectional epidemiological study. Data were obtained from the information technology department of the Unified Health System - DATASUS. The variables researched were: total hospitalizations, sex, color/race, age group, deaths and mortality rate. The age group surveyed was individuals from zero to 19 years old. The research period was delimited between the months of January 2010 and December 2020. Results: There were 5,909 hospitalizations in the studied period. In 2010 and 2020, 627 and 290 hospitalizations were recorded, respectively. Males reported 3,127 hospitalizations, and females 2,782. The brown color/race registered 2,115 hospitalizations. The most affected age group was 15 to 19 years old, with 2,136 cases. The total number of deaths was 194. The average mortality rate was 3.28. Conclusions: Hospitalizations for chronic rheumatic heart disease show a decreasing curve in recent years in Brazil. The epidemiological profile of hospitalizations between 2010 and 2020 was characterized by male adolescents, brown, aged between 15 and 19 years. The number of hospitalizations in 2020 may have been influenced by the pandemic caused by COVID-19. 109103 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOGERIATRICS The Kansas City Cardiomyopathy Questionnaire Evaluation in Elderly Patients with Diabetes and Pre-Diabetes CAROLINA JERONIMO MAGALHAES1, Matheus Dantas Soeiro3, Sabrina Barreto Braga Pires3, Maria Eduarda Borges Matias3, Ellen Beatriz Sobral3, Carolina De Carvalho Moury Fernandes3, Jessica Myrian de Amorim Garcia2, Francisco Bandeira1 (1) UNIVERSIDADE DE PERNAMBUCO; (2) HOSPITAL AGAMENON MAGALHAES; (3) FACULDADE PERNAMBUCANA DE SAUDE Introduction: Diabetes mellitus (DM) and heart failure (HF) often co-exist, and the number of people with both diseases is increasing due to ageing and better treatment. DM contributes to the progression of HF, commonly associated with worsening of symptoms. Quantifying the quality of life (QOL) in HF is extremely important especially in the elderly, in order to maintain good health and personal satisfaction through life. Objectives: Evaluate the QOL of elderly based on the Kansas City cardiomyopathy questionnaire (KCCQ) associated with DM, pre-DM and normoglycemia in a large tertiary center. Methods: A single-center analysis of in-patients aged >=65 years presenting with HF from August 2020 to January 2022 in a Brazilian cardiology teaching hospital. KCCQ was performed considering QOL 15 days prior to admission. Scores scaled 0-49 represented poor health status, and 50-100 good health status. Based on glycated haemoglobin (HbA1c) the elderly were diagnosed with DM, pre-DM or normoglycemia. Results: A total of 182 patients were studied. The mean age was 73 +- 6 years, 54.3% were men. Study population had 88.8% prevalence of hypertension and 51.5% of chronic kidney disease. The mean level of HbA1c was 6.6 +- 2.0%, minimum of 4.1% and maximum of 14.7%. Based on HbA1c, 45.8% had DM, 23.6% pre-DM and 30.6% normoglycemia. Mean score for KCCQ was 54.6 +- 19.65. QOL was considered good in 52% patients and bad in 48%. There was no association between HbA1c levels and poorer QOL in the elder patients. Conclusion: We found no differences in QOL specific evaluation for HF in elderly patients with or without DM or pre-DM. 109114 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY Clinical and Epidemiological Profile of Patients Followed in a Specialized Outpatient Clinic of Cardioncology VINICIUS PEREIRA DANTAS1, Rafael Alves da Silva1, Ademar Alexandre de Morais1, Rosiane Viana Zuza Diniz1, Kelton Dantas Pereira1, Kelson Kemuel Confessor de Sousa1 (1) Hospital Universitario Onofre Lopes - HUOL UFRN Introduction: Considering the aging of the population and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. The cardiotoxicty is one of the main and most feared complications of cancer treatment. It can manifest itself in several ways including, with heart failure (HF) being the most frequent and most severe. So, oncologist and cardiologists should undertake the therapeutic option for a cancer patient to minimise cardiotoxicity without compromising anticancer efficacy. Aim: Identify the cardiotoxicity risk in cancer outpatients referred to the cardio-oncology clinic in a tertiary hospital and determine the treatment plan at the referral time. Methodology: Cross-sectional, observational and descriptive study, conducted between September 2018 and September 2021, involving 60 adults, at the first visit in a cardio-oncology clinic of a tertiary hospital. Results: The majority of patients were women (68.3%, n = 41), white (35%, n = 21). The mean age was 56 +- 15.5 and the most frequent aetiology was breast neoplasia (40%, n = 24). The levels of high to very high for cardiotoxicity risk were prevalent (71.6%, n = 43). At the first visit, 45 patients (75%) had already started chemotherapy and/or radiotherapy treatment against cancer and 38 (63.3%) of the patients were diagnosed with heart failure. Conclusion: The risk for cardiotoxicity in this population was high, as well as the presence of heart failure and use of anti-neoplastic treatment prior to consultation in a specialized outpatient clinic. The optimal timing and mechanisms for referral need to be studied and implemented. Referral to the specialist in cardio-oncology allows an early recognition of subclinical signs and symptoms, detecting and preventing CV side effects in cancer patients. 109139 Modality: E-Poster Young Researcher - Non-case Report Category: DYSLIPIDEMIA High-Dose of Potent Statins May not be Sufficient to Achieve Therapeutic Goals of Ldlc and Non-Hdl Cholesterol in Patients at Very High Cardiovascular Risk GISELI CASARINI1, Natan Alevato Donadon1, Gabriel Tamanaha Pacheco1, Rafael Ferreira e Bringel1, Sara Regina Alcalde Domingos1, Andre Arpad Faludi1, Daniel Branco de Araujo1, Natasha Soares Simoes dos Santos1, Adriana Bertolami1, Luiz Paulo Bastos Schmidt1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: High-dose of potente statins are first-line and mandatory therapy to reduce LDL-c among very high cardiovascular risk patients. The Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis of the Brazilian Society of Cardiology (SBC) recommends a target of LDL-c below 50 mg/dL or non-HDL cholesterol (NHDLc) <80 mg/dL. Objective: Evaluate the amount of very high-risk patients using the initial treatment recommended by the brazilian guideline that achieved the LDL-c and NHDLc therapeutic goals. Methods: This is a cross-sectional observational study that included 1122 very high cardiovascular risk patients (significant atherosclerotic disease with or without clinical events or obstruction >=50% in any arterial territory), treated in outpatients clinics between January and March of 2022, in a tertiary care hospital in Brazil, using atorvastatin 40 mg or 80 mg daily. Exclusion criteria were: use of atorvastatin in a dose lower than 40 mg/daily or use of other statins. Data from the electronic medical record were collected regarding lipid profile, such as LDL-c and NHDLc, age and sex. RESULTS A total of 1122 patients were evaluated and 1012 were included. Mean age was 68.8 years (SD 9.2), 634 (62.4%) were men. Regarding statin use, 613 (60.6%) patients used atorvastatin 80 mg/daily and 399 (39.4%) used atorvastatin 40 mg/daily. Average LDL-c was 83.1 mg/dL (SD 29.5) and NHDLc was 113.5 mg/dL (SD 35). The mean TC was 152 mg/dL (SD 29.5), HDL-c was 39.5 (SD 11.8) and of TG was 154.9 (SD 85.6). Ninety two (9%) patients had LDL-c <50 mg/dL and 133 (13.14%) patients had NHDLc <80 mg/dL. Conclusion: The low amount of patients in this population that achieved LDL-c and NHDLc target shows that with high-intensity statins monotherapy may not be sufficient. These data suggest that in very high-risk patients, combined lipid-lowering therapy, in the initial phase, should be considered. 109153 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION A Nationwide Service of Tele-Electrocardiography: The Telehealth Network of Minas Gerais MILENA SORIANO MARCOLINO1, Maria Cristina da Paixao1, Leonardo Bonisson Ribeiro1, Paulo Rodrigues Gomes1, Breno Max Horta Melo1, Gabriela Miana de Mattos Paixao1, Antonio Luiz Pinho Ribeiro1 (1) Centro de Telessaude do Hospital as Clinicas da Unniversidade Federal de Minas Gerais Introduction: Cardiovascular diseases are the main cause of death in Brazil and in many developing middle-income countries (LMIC). Access to specialized cardiac care remains precarious in most of these places. Objective: To describe the experience of the Telehealth Network of Minas Gerais of developing and implementing the Brazilian Nationwide Service of Tele-Electrocardiography. Methods: Remote points, located primarily on primary healthcare units, received a standard computing system including a computer, connected to the internet, and a digital electrocardiogram (ECG). ECG signal is captured by the computer, using in-house developed software, and uploaded to a central server, where they are pre-processed, including automatic ECG measurements. A web-based interface is available for the cardiologists to analyze and interpret ECG exams, including tools for magnifying and re-measuring the ECG waves and intervals and a support system for improving the quality of the report. Quality is regularly audited. This system, initially implemented in the state of Minas Gerais in 2006, has been implemented in other Brazilian states since 2017. Results: The service is available 24 x 7. Emergency exams or those with extreme abnormal automatic findings are prioritized and reported in less than 10 minutes; the others are analyzed in less than 2 hours. Since 2006, over 6 million ECGs have been analyzed and the system is now available in 1199 cities in 12 Brazilian states. The majority of the remote points are in primary care centers, but some are in small hospitals and emergency care units. The system is cost-effective, having generated economy of over R$ 345,000,000 with the reduction of referrals to other cities, and allows access to a basic cardiological exam in places where it was not available. More recently, the dataset of ECGs was organized and linked to mortality data (the CODE study) and is being used in epidemiologic and artificial intelligence studies. Conclusions: Telehealth tools can be used in LMIC countries to provide cost-effective access to high quality ECG diagnosis in large scale. This kind of service can also help to build datasets for relevant research for local communities and the development of advanced artificial intelligence. The availability of these tele-ECG systems may have impact in cardiovascular care in LMIC. 109170 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Prognostic Value of Stress Cardiac Magnetic Resonance at 3 Tesla in Patients with Known or Suspected Coronary Artery Disease SOMLUCK PUNAWAKUL1, Pairoj Chattranukulchai2, Monravee Tumkosit3, Yongkasem Vorasettakarnkij2 (1) Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; (2) Cardiac center, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; (3) Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Adenosine stress CMR is playing an important role in diagnosis of coronary artery disease (CAD). Objectives To assess the prognostic value of adenosine stress CMR at 3 Tesla to predict clinical outcomes during two years of follow-up in patients with known or suspected CAD. Methods: A retrospective cohort study in patients who underwent adenosine stress CMR at 3 Tesla between 1 Sep 2017-31 Aug 2019 at a tertiary hospital in Bangkok, Thailand. The primary outcome includes composite outcomes of CAD-related death, non-fatal MI, and revascularization. Results: Total of 633 patients were analyzed (age 66.21 +- 12.60 years, 53.7% male, 31.9% known CAD). The result of CMR was positive in 215 cases (33.97%), and 118 patients (2.7%) had myocardial scar. We observed 5 CAD-related deaths, 10 non-fatal MI, and 94 revascularizations within 2 years of follow-up. Positive adenosine stress CMR demonstrated a significant association with both primary outcome (43.4% vs. 2.9%, p = <0.001), and secondary outcome (61.4% vs. 25.4%, p = <0.001). The severity of perfusion defect was significantly associated with the primary outcome in both patients with and without myocardial scar groups. Among the patients without scar, primary outcome in the no ischemia, mild/moderate, and severe ischemia group are 2.38%, 16.28%, and 53.03% (p = <0.001), respectively. Among the patients with scar, the primary outcome were 14.29%, 22.73%, and 70.21% (p = <0.001), respectively . Conclusions: In this cohort study, positive adenosine stress CMR at 3 Tesla is a powerful tool to predict clinical outcomes in patients with known or suspected CAD. The severity of myocardial ischemia and the presence of myocardial scar could help identifying high-risk patients. More study Further studies are warranted. 109179 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Effects on Depression and Anxiety Comparing Resistance Training According to Trained Muscle Group in Low Functional Capacity Heart Failure Patients JAVIER ELIECER PEREIRA RODRIGUEZ1, Jorge Lara-Vargas2, Fernando Rivera-Theurel3, Magalli Diaz-Bravo1, Eduardo Leyva-Valadez2, Luis Fernando Ceballos-Portilla1, Arizbeth De Jesus-Guerra1, Salvador Aguilar-Nava1, Sebastian De Marcos-Sanchez1, Guadalupe Montserrat-Pineda1 (1) Centro de Estudios e Investigacion FISICOL. Colombia; (2) Cardio Fit. Mexico; (3) University of Toronto. Canada Introduction: Heart Failure patients (HF) are characterized by decreased functional capacity and quality of life. The prevalence of depression of 25% in newly diagnosed HF and up 50% in advanced stages of HF. Anxiety prevalence in HF patients can up to 40%. Objetive: Determine the difference between strength training of upper versus lower limbs in the depression and anxiety scale of patients with heart failure with low functional capacity within a cardiac rehabilitation program. Methods and materials: Prospective randomized study with 412 cardiac rehabilitation participants comparing 2 groups (Aerobic exercise (60-80%) + Group 1: MMSS Strength (40-60%) and Group 2: MMII Strength (40-60%). An exercise stress test, a 6-minute walk, a 1-repetition maximum test, depression and anxiety with the HAD test were performed. Measurements were done after the 24 sessions of 60 minutes and in the absence of psychological intervention. In the statistical analysis, normality was evaluated by means of Kolmogorov-Smirnov and, subsequently, the analysis of variance ANOVA. Results: 411 finished the intervention and it was possible to determine that both groups improved the depression levels GE1: 21%vs11%; GE2: 27%vs7%; p = 0.001 and anxiety GE1:13%vs7%; GE2:15%vs4%; p = 0.001. Conclusion: Strength training combined with aerobic exercise reduces depression and anxiety in HF. 109183 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY Carvedilol or Exercise Training: What is the Best Approach to Prevent Baroreflex During Doxorubicin Treatment? FILIPA DANIELA COSTEIRA MACHADO1, Ana Afonso1, Filipa Machado1, Angela Amaro-Leal1, Miguel Meira-Cruz1, Isabel Rocha1, Vera Geraldes1 (1) Faculdade de Medicina e Centro Cardiovascular da Universidade de Lisboa Doxorubicin (DOX) is a highly effective anticancer drug, but its effectiveness is offset by dose-related side effects, including autonomic dysfunction and cardiotoxic effects. Exercise training (ET) and b-blockers have been suggested to prevent cardiotoxicity. ET reduce sympathetic activity and increase parasympathetic activity. Beta-blockers reduce sympathetic activation and improve cardiac function. Despite extensive research it is not yet clear which therapeutic regimen is best suited to prevent or reduce DOX side effects. In our work, we compare the efficacy of two approaches: carvedilol (CVD) and a non-pharmacological intervention, an exercise protocol (ET) with treadmill training in an animal model of DOX. Female Wistar rats were divided into 4 groups: Doxorubicin (DOX; ip cumulative dose 16 mg/kg, 1 time/week, for 4 weeks), DOX with ET (DOX+EX;treadmill, 25 cm/sec for 30 min, 5 times/week), DOX with CVD (DOX+CVD:10 mg/kg, orally, 5 times/week, for 4 weeks) and controls (CTL ip with saline). At the end of the protocol, animals were anaesthetized, and blood pressure (BP), electrocardiogram, heart rate (HR) and respiratory rate (RF) were recorded. Baroreceptor and chemoreceptor reflexes were tested, and baroreflex gain and sensitivity, and chemoreflex sensitivity were calculated. HRV was determined to estimate sympathetic and parasympathetic activity. Our results show that DOX treatment induced a significant decrease in systolic BP (CTL:150.1 +- 5.338; DOX:103.1 +- 10.19 mmHg, p = 0.0127) and mean BP (CTL:129.0 +- 3.520; DOX 90.38 +- 10.08 mmHg, p = 0.0072), and in HR (CTL:379.5 +- 54.34; DOX:288.3 +- 53.11 bpm, p = 0.0284), compared with the CTL group. The ET protocol normalises systolic BP (122.4 +- 29.85 mmHg), mean BP (94.51 +- 20.08 mmHg) and HR (350.4 +- 22.18 bpm). Administration of CVD during DOX treatment significantly restored HR to near-physiological levels (368.6 +- 16.23 bpm p = 0.0359). DOX treatment resulted in an increase in baroreflex gain compared to the CTL group. CVD treatment, similar to the ET effect, decreased baroreflex gain compared with the DOX group (DOX:4.738 +- 2.771; DOX+EX:0.5046 +- 0.06773; p = 0.0473 and DOX+CVD:0.5516 +- 0.05672 bpm/mmHg; p = 0.0376) and also restored BEI, BRS and SDNN to normal values. No significant changes in chemoreflex sensitivity, RF and frequency domain indices were observed. Overall, these results suggest that CVD and ET improve baroreflex through HR modulation. However, ET can be considered the best strategy as it acts on both autonomic branches. 109234 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Effect of Ketogenic Diet Vs. Recommended Diet on Body Composition and Muscular Functional Capacity in Obese Individuals JOAO MOTARELLI1, Juliana Tieko Kato1, Marilia Andrade Papa1, Maria Cristina de Oliveira Izar1 (1) Universidade Federal de Sao Paulo Introduction: The reduction of body mass (BM) in obese individuals has been considered a modifiable risk factor for cardiovascular diseases (CVD) morbidity and mortality. However, the potential benefits of ketogenic diet in BM reduction may be compromised due to the reduction off strongh predictors of CVD such as lean mass (LM) and muscle strength, which may inadvertently affect the individual's muscular functional capacity (MFC). Objective: To evaluate changes in body composition and MFC in physically inactive obese patients undergoing one of two different low-calorie diets over a 6-month period. Methods: We included 25 physically inactive patients with grade I or II obesity, of both genders, with a mean age of 40 years, followed for 6 months through periodic medical and nutritional care, allocated to the Dukan's Diet (DD) group (n = 11) who received the nutritional recommendations specified by the Dukan Diet (ketogenic diet) or the Recommended Diet (RD) (n = 14), who received nutritional guidelines based on the 2014 Food Guide for the Brazilian Population. Double absorbance x-ray (DEXA) was used for analysis of LM, and Body Fat (BF); Biodex(r) Multi-joint System 3 isokinetic dynamometer was used for MFC analysis of the knee extensor muscles (Peak torque at 60deg/s - PT and its variable corrected by BM - PT/BM). Food intake was quantified via 3-day dietary recall and ketosis analyzed through urine stripes. Analyzes were performed at baseline, 05, 30, and 180 days. Results: Significantly higher consumption of protein and lower consumption of carbohydrates and fiber were observed in the DD group compared to RD as the presence of ketosis in urine (in 05 and 30 days). At the end of the study, it was observed that both interventions promoted significant reductions in BM (DD P < 0.001; DR P < 0.001) and BF (DD P < 0.001; RD P < 0.001), however, only DD presented significant reductions of LM (P < 0.031), PT (P < 0.001), PT/BM (P < 0.001). Comparison between groups at 180 days showed significantly lower measures for BF (P < 0.031) in the DD group. Conclusion: DD promoted more expressive reductions in BF and LM at the expense of a loss of MFC even with a high protein intake. Longer-term studies are needed to understand whether the reduction in MFC could lead to functional impairment and/or increased risk for CVD in this population as a result of the practice of this diet. 109235 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Preoperative Lung Cancer Patient Risk Assessment with Cardiopulmonary Exercise Testing BIANCA FELDMAN1, Rodrigo Mazza1, Bruno Dias1, Gabriel Moraes1, Joao Magalhaes1, Carlos Gil Ferreira3, Tatiane Montella3, Anderson Nassar2, Gustavo Nobre2, Marcelo Kalichsztein2, Leandro Toledo1, Fabricio Braga1 (1) Laboratorio de Performance Humana(LPH); (2) Casa de Saude Sao Jose (CSSJ); (3) Oncoclinica Background: The role of aerobic capacity as a predictor of surgical risk (SR) has been highlighted, especially in cancer patients. Cardiopulmonary exercise testing (CPET) is the gold standard in this assessment. Objective: To characterize and identify risk predictors among lung cancer (LC) patients evaluated with the CPET. Materials and methods: Cross-sectional analysis of LC patients who underwent CPET as part of the SR assessment for lung resection. Before CPET, all patients performed rest spirometry to determine forced vital capacity (FVC) and end-expiratory volume in the first second (FEV1). SR was classified by an algorithm based on peak exercise VO2 (pVO2) and the slope of the ratio between minute ventilation (VE) to carbon dioxide (VCO2) output (VE/VCO2 slope) in low, medium, high and very high SR. A multivariate logistic regression model (MLRL) was created to identify predictors of low SR. Results: Ninety-eight patients were analyzed (44.9% men, 71 +- 9.1 years). The mean pVO2 was 16.7 +- 4.2 ml/kg/min (77.9 +- 17% of the predicted values), and the mean VE/VCO2 was 36.6 +- 6.4. The FVC and FEV1 were 2.66 +- 0.8 L and 2.08 +- 0.65 L, respectively. According to the SR, 38 (38.6%), 31 (31.6%), 26 (26.5%) and 3 (3.1%) were classified as low, moderate, high and very high, respectively. Low SR patients were younger (67.8 +/- 9.3 vs. 73.1 +- 8.6 years [p = 0,005]), showed a higher FVC (2.87 +- 0.88 vs. 2.52 +- 0.73 [0.043]) and FEV1 (2.34 +- 0.70 vs. 1.89 +- 0.55 L [p = 0.001]), and trended to a lower COPD prevalence (25 vs. 43.5% [0 = 0.075]) than other risk patients. In the MLRL, age (OR = 0.93 [95% CI 0.88-0.98]) and FEV1 (OR = 24.4 [95% CI 2.2-266.3]) were independently associated with a low SR. Conclusion: (1) More than 60% of lung cancer patients are not at low risk when assessed by CPET; (2) advanced age and reduced FEV1 increased the odds of a higher SR. These data can guide prehabilitation strategies to reduce perioperative morbidities for LC patients. 110340 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Pulmonary Vein Reconnection Patterns in Atrial Fibrillation Catheter Ablation Redo Procedures: Single-Center, Cross-Sectional Study GABRIEL ODOZYNSKI1, Isabella Bianco3, Helcio G. Nascimento1, Andrei Lewandowski1, Mauricio L. Spessatto1, Clovis Froemming1, Grazyelle Damasceno1, Alexander Dal Forno1, Andre Pacheco Silva1, Andre d'Avila1 (1) Hospital de Cardiologia SOS Cardio; (2) Instituto de Cardiologia de Santa Catarina; (3) Universidade do Sul de Santa Catarina Introduction: Different electro-anatomic recurrence patterns were previous described. Yet, pulmonary vein (PV) electric reconnection to left atrium is the typical finding after atrial fibrillation (AF) catheter ablation recurrence. Aims and Method: We aim to evaluate AF ablation recurrence patterns in a cross-sectional, single-center study of recurrent AF patients who had underwent to a 2nd ablation procedure (REDO). Results: Of 47 enrolled patients to REDO, 31 patients had paroxysmal AF (<=7 days-PAF) and 16 patients persistent AF (>7 day <=1 year -AF-Per). PV reconnection were confirmed in 21 (68%) and 16 (62%) patients of PAF and AF-Per. From 113 targeted PVs in PAF and 58 in AF-Per (30%) and 18 (31%) of PVs were reconnected, respectively. 10 (32%) PAF and 6 (37%) in AF-Per patients have maintained PV isolation during REDO procedure. 6 (19%) and 3 (18%) patients had 1 reconnected PV, 11 (35%) and 6 (37%) had 2 reconnected PVs in PAF and AF-Per groups. Only 2 patients in PAF and 1 in AF-Per have presented all PVs reconnected during REDO procedure (2 left common trunk). Right PVs were reconnected in 11(61%) of PAF patients. Cavo-tricuspid isthmus flutter ablation were performed in 6 patients in PAF group. Left atrial appendage was electrical isolated in 1 AF-Per patient during REDO procedure. At the first procedure, left atrium posterior wall ablation was performed in 6 (19%) and 8 (50%) of PAF and AF-Per. The posterior wall reconnection was confirmed in 2 AF-Per procedure. Left common trunk were reconnected in 2 (6%) and 2 (12%) in PAF and AF-Per. Conclusion: PV reconnection is the typical finding in patients with recurrent AF after catheter ablation. Right PVs reconnection was the common described pattern. 109269 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Differences in the Compositions of the Gut Microbiota in Patients with Acute Myocardial Infarction in the Presence or Absence of Type 2 Diabetes Mellitus JULIANA TIEKO KATO1, Joao Henrique Fabiano Motarelli1, Andrey Santos2, Mario Jose Abdala Saad2, Maria Cristina de Oliveira Izar1, Carolina Nunes Franca1, Henrique Andrade Fonseca1, Francisco Antonio Helfenstein Fonseca1 (1) Universidade Federal de Sao Paulo; (2) Universidade Estadual de Campinas Introduction: There is clear evidence that the composition of the gut microbiota (GM) plays an important role, not only in extracting energy from food, but also as a key endocrine organ, producing metabolites that impact the pathogenesis of type 2 diabetes mellitus (DM). Despite advances in metagenomics techniques, it is still difficult to establish a microbial signature in DM due to numerous confounding factors, such as the association with other pathologies, diet, drug and geographic location. Objective: To identify changes in the GM composition in individuals with DM or without DM [prediabetic (PDM) and non-diabetic (NDM)] in the first 24 hours of acute ST elevation Myocardial Infarction. Methods: Eighty-five patients were included, metagenomic analysis was performed through stool using a technique that is based on DNA extraction and amplification of the 16S rRNA gene. Data were processed by the Miseq Illumina platform and analyzed using the Illumina 16S Metagenomics software. Other analyzes were performed using the SPSS version 21. The significance level was p < 0.05, and when necessary, the p-values of the fecal samples were adjusted using the False Discovery Rate (FDR) multiple comparison test. Subjects were divided into groups according to glycated hemoglobin values, <5.7% (NDM), 5.7 to 6.5% (PDM) and >6.5% (DM). Results: Relative abundance analysis showed significant differences between the phyla Firmicutes (P = 0.05) and Verrumicrobia (P = 0.02) and the genus Akkermansia (P = 0.03) between the NDM vs DM groups. When the values were adjusted by FDR, we found a significant increase in the phylum Firmicutes (P-FDR = 0.035) and class Clostridia (P-FDR = 0.041), as well as a decrease in the phylum Verrucomicrobia (P-FDR = 0.035) and its class Verrucomicrobiae (P-FDR = 0.045) in NDM when compared to DM. Conclusion: The present study showed that the composition of the intestinal microbiota differed between the NDM vs DM groups after acute myocardial infarction, with a duality in the results, where an increase (Firmicutes and Clostridia) and a decrease of bacteria considered beneficial (Verrucomicrobia) were observed. 109255 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Application of the Prisma Methodology in a Systematic Study on the use of Radiofrequency Ablation as an Alternative for the Treatment of Obstructive Hypertrophic Cardiomyopathy ANA LIGIA VALERIANO DE OLIVEIRA1, Ana Ligia Valeriano de Oliveira1, Andressa Pimentel Afiune1, Jhenefr Ribeiro Brito1, Vitoria Lorrane dos Santos1, Thais Aratk Marques Taia1, Danilo Borges de Sousa1, Anna de Paula Freitas Borges1, Andressa Morgado Parreira1, Lucas Eduardo Almeida Franca1 (1) Pontificia Universidade Catolica de Goias Obstructive hypertrophic cardiomyopathy is a genetic disease capable of causing changes in the structure and function of the myocardium muscle. Hypertrophy results in left ventricular obstruction and symptoms of heart failure, exertional syncope, or sudden cardiac death. Radiofrequency myocardial septal ablation is a treatment option for symptomatic and drug-refractory cases. It is a less invasive method and can be used for septum reduction in patients at high risk for surgeries such as myectomy and alcohol ablation. The study seeks to evaluate the feasibility, efficiency and outcome of treatment with radiofrequency ablation in obstructive hypertrophic cardiomyopathy. This is a systematic review based on the methodological recommendations Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. The identification and selection of articles was conducted by two independent researchers between October and December 2021 on the platforms PubMed, Scientific Electronic Library Online and Latin American and Caribbean Literature. The filters used were "human" and "published in the last 10 years". The included studies were in English and Portuguese. The descriptors used were obstructive hypertrophic cardiomyopathy, treatment and radiofrequency ablation that were associated with the Boolean operator AND. We found 66 articles, after applying the inclusion and exclusion criteria, we selected 10 articles that were used in this review. The studies analyzed showed a reduction in the left ventricular outflow tract gradient, septum thickness, mitral regurgitation volume and pro-BNP. Furthermore, ablation showed the ability to suppress ventricular tachycardia in all patients. There was improvement according to the NYHA functional class in four articles, with statistical significance. It was analyzed in a study that the procedure, combined with imaging techniques with a mixture of intracardiac echocardiography and CARTOSound, enabled a more effective mapping of the affected area and avoided damage to the conduction tissue. Finally, the radiofrequency septal ablation technique proved to be a safe and less invasive option, with a shorter hospital stay. Radiofrequency septal ablation allows a significant reduction in the left ventricular outflow tract gradient, in addition to improving the NYHA functional class, thus being an alternative to alcohol septal ablation and myectomy, but later studies comparing it with others invasive methods become necessary. 109270 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Driveline Dressings Used in Patients with Heartmate and Their Relationship with Local Complications up to 30 Days Post-Operative RAFAELA BATISTA DOS SANTOS PEDROSA1, Natalia Balestra2, Roberta Cunha Matheus Rodrigues1, Adryel Vieira Caetano da Silva2 (1) Faculdade de Enfermagem da Universidade Estadual de Campinas; (2) Hospital Sirio-Libanes Introduction: Driveline infections are common in patients with left ventricular assist devices and an important cause of morbidity and mortality. Nurses play a fundamental role in the care of the driveline, however, scientific evidence regarding dressing standardization is lacking. Objective: To describe the categories of dressings used in the driveline of patients using the HeartMate (HM) device and the incidence density of local complications (infection, bleeding and pressure injuries) within 30 days of the postoperative period. Methods: This was a retrospective cohort of patients hospitalized in the Intensive Care Unit (ICU) after HM II and III implant surgery in a private hospital in the state of Sao Paulo, Brazil, between 2015 and 2021. The data source was the hybrid medical records of the participants. We performed a descriptive analysis and Fisher's exact test and statistically significance level of 5% was considered. Incidence density was calculated for infection, bleeding and pressure injury. The study project was approved by the local Ethics Committee (No. 4,593,315). Results: The results showed a high variability of dressings with 22 different categories being recognized and for each participant, an average of 2.2 +- 1.0 dressings. The dressing categorized as C6 (Chlorhexidine, Excilon, Gauze and IV3000) was the most used (45.4%), followed by C13 - ChloraPrep, Biatain Ag, Gauze and IV3000 (31.8%) and C9 - Protosan, Excilon, Gauze and IV3000 (22.7%). Bleeding was more frequent in categories C6 (9.0%), C11 - ChloraPrep, Gaze, Excilon and IV3000 (9.0%) and C13 (9.0%), while pressure injury was identified in only two categories. Subjects using FlexiTrak stabilizer had the highest rate of bleeding (50.0%) and those using Hollister had the highest infection rate (61.1%) and pressure injuries (11.1%). The participants who presented bleeding had higher median values of cardiopulmonary bypass time (112.5 minutes) when compared to those without bleeding (100 minutes); p = 0.029. Infection incidence density was the highest, 43.6/1,000 person-days, mainly in men (55.5/1,000 person-days), using the Heartmate III (48.3/1,000 people-day) and who used two or more categories of dressings (47.2/1,000 person-days). Conclusion: The infection was the complication with the highest incidence density; the findings point to a standardization with the use of chlorhexidine, absorbent foam impregnated with silver and transparent film, as well as the use of a stabilizer. 109282 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Differences in the Composition of the Intestinal Microbiota in Patients with St-Segment Acute Myocardial Infarction JULIANA TIEKO KATO1, Joao Henrique Fabiano Motarelli1, Andrey Santos2, Mario Jose Abdala Saad2, Maria Cristina de Oliveira Izar1, Carolina Nunes Franca1, Henrique Andrade Fonseca1, Francisco Antonio Helfenstein Fonseca1 (1) Universidade Federal de Sao Paulo; (2) Universidade Estadual de Campinas Introduction: The study of the gut microbiota (GM) in coronary artery disease is an emerging area, because metabolites generated by GM seem to be involved in the progression of the disease, with the proatherosclerotic metabolite N-oxido-trimethylamine (TMAO) being the best described. Currently GM is considered a potential therapeutic target, but few studies have evaluated the changes and influence of GM composition in post-acute myocardial infarction. Objective: To identify changes in the GM composition of individuals in the first 24 hours (baseline), 30 and 180 days after ST-segment elevation acute myocardial infarction. Methods: 173 patients were included and 355 stool samples were sequenced, the metagenomic analysis was performed using the technique that is based on DNA extraction and amplification of the 16S rRNA gene, the data were processed by the Miseq Illumina platform and analyzed using the Illumina software 16S Metagenomics. Other analyzes of non-parametric variables were performed using Friedman test for paired samples, using SPSS 21 version. TMAO levels were measured in urine by liquid chromatography with a mass spectrometer from 23 subjects. The significance level was p < 0.05, and when necessary the p-values of the fecal samples were adjusted by the False Discovery Rate (FDR) multiple comparison test. Results: The analysis between times showed a more inflammatory profile at baseline when compared to 30 days, with a decrease in beneficial bacteria belonging to the phylum Bacteroidetes (P-FDR = 0.04) and genus Faecalibacterium (P = 0.04), in addition to the increase in Proteobacteria considered to be pro-inflammatory bacteria (P-FDR = 0.04). However, over time, GM showed an improvement in 180 days when compared to baseline, with a significant increase in bacteria producing butyrate, a short-chain fatty acid with a crucial role in human health, phylum Bacteroidetes (P = 0.01), family Lachnospiraceae (P-FDR = 0.04) and genus Faecalibacterium (P < 0.01), in addition to the increase in Prevotella (P = 0.02). Interestingly, other important analyzes of the composition of GM, showed a worsening of richness and diversity decreased at 30 and 180 days when compared to baseline, in addition to the increase of TMAO over time (P = 0.03). Conclusion: A more inflammatory profile was observed at baseline with improvement at 180 days after infarction, however TMAO increased over time, accompanied by a decrease in richness and diversity. 109304 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Time between the Emergency Room Admission, Diuretic Infusion, and the Readmission Risks Among Patiens with Decompensated Heart Failure NICHOLLAS COSTA ROSA1, Nichollas Costa Rosa1, Maria Antonieta Moraes1 (1) Programa de Pos Graduacao em Ciencias da Saude: Cardiologia da Fundacao Universitaria de Cardiologia Introduction: The treatment of Heart Failure (HF) with diuretics substantially impacts this syndrome's prognostic. Data suggest that patients at a higher risk of furosemide intake in the early stages of the disease can decrease the mortality rates. Objetivos: Monitor the time between the patient's admission into the emergency room and were administered the first dose of diuretics among patients with HF and their risk of readmission within 30 days of hospital discharge using the LACE. Methods: Prospective and retrospective cohort study conducted with decompensated HF patients, supported by echocardiographic data, of both sexes with >=18 years old, treated in a cardiology emergency (ES) from August 2018 to December 2018. 2019. The parameters used were diuretic infusion time, length of stay in the ES, and readmissions. The risk of readmission was classified using the LACE score as low (0 to 4), moderate (5 to 9), and high (>9) risk. The Chi-square test check for categorical variables. The Mann-Whitney test for the time spent in the SE and time of diuretic infusion. Results: We analyzed 361 medical records of mostly male patients (56%), aged 68 +- 12 years. There was a predominance of ischemic HF (49%), reduced ejection fraction (57%), functional class III (73%), and hemodynamic profile B (81%). After hemodynamic stabilization (60%) were discharged, and (39%) required 6 (4-12) days of hospitalization. The time between admission and infusion of the diuretic was 87 (60-128) minutes. Of these, 26.3% infused up to <=60 and 73.7% in >60 minutes. The 40 mg dose of diuretic was used in 72% of them. There was a significant relationship between receiving a diuretic for <=60 minutes and staying in the ES < 6 hours (early discharge), p < 0.05. The LACE score showed that 62% of patients had a moderate risk of unplanned readmission within 30 days. Patients at high risk for readmission (37%) were associated with altered pulmonary auscultation and the presence of jugular swelling (p < 0.05). After 6 months, 15% of the patients died, 9% lost contact and 75% were followed up. Of these, 37% were readmitted, 21% within 30 days and 46% within 180 days. Conclusion: The time between admission and intravenous infusion of diuretics in this population with acute HF was sub-optimized; however, patients who received the drug earlier were in the emergency department for a shorter time. The risk of readmission through LACE was effective in 34% of patients. 109307 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Prevalence of Genetic Alterations in Individuals with Cardiomyopathies Without Defined Aetiology in a Tertiary Hospital DIOGO MACIEL SILVA AZEVEDO1, Diogo Maciel Silva Azevedo1, Kelson Kemuel Confessor de Sousa1, Fabio Mastrocola1, Rosiane Viana Zuza Diniz1 (1) Hospital Universitario Onofre Lopes - HUOL Introduction: Cardiomyopathies are a heterogeneous group of structural and functional disorders of the heart muscle, with different etiologies and phenotypic expressions, in the absence of congenital, valvular, coronary diseases or arterial hypertension compatible with the myocardial alterations found. The diversity of clinical presentation makes the etiological definition difficult, and pathogenic genetic alterations are important in this definition. Objective: To determine the prevalence of genetic alterations in individuals with cardiomyopathies without defined aetiology in a tertiary hospital. Method: This is a retrospective, observational and longitudinal study involving 39 individuals with cardiomyopathy without an initially clarified diagnosis, inhospital and outhospital patients, follow-up in a tertiary hospital during the years 2020 to 2022, with identification of the genetic profile and phenotype of presentation assessed by echocardiographic parameters. Data were presented as means and proportions. Results: The mean age was 45.7 years+-14.5 years, with an even distribution regarding gender (51% men). The prevalence of positivity in the genetic test was 33.3% and the most frequent presentation phenotype was hypertrophic cardiomyopathy (53%), followed by dilated cardiomyopathy (33.3%). Among the 21 individuals with hypertrophic cardiomyopathy, 47% had a positive genetic test, with the MYBPC3 and MYH7 genes being the most frequently identified in pathogenic or probably pathogenic mutations, representing 70% of positive cases. Conclusion: The prevalence of genetic alterations in our population was high, especially in those with a hypertrophic phenotype, reinforcing the importance of determining the genetic profile and tracking family members in these patients. 109309 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Histopathological Changes in Endocardial Layer is Related to Myocardial Perfusion Defects in Chronic Chagas' Cardiomyopathy CAMILA GODOY FABRICIO1, Denise Mayumi Tanaka1, Jose Antonio Marin-Neto1, Luciano Fonseca Lemos de Oliveira2, Alessandra Arantes de Resende1, Fernando Fonseca Franca Ribeiro1, Alexandre Todorovic Fabro1, Sabrina Setembre Batah1, Jorge Mejia Cabeza3, Minna Moreira Dias Romano1, Andre Schmidt1, Marcus Vinicius Simoes1 (1) Medical School of Ribeirao Preto - University of Sao Paulo, Sao Paulo, Brazil; (2) Physiotherapy Department - Federal University of Minas Gerais, Brazil; (3) Hospital Israelita Albert Einstein, Sao Paulo, Brazil Background: Chronic Chagas' cardiomyopathy (CCC) have showed, in previous studies, a high prevalence of microvascular myocardial perfusion defects (MPD) that may participate in the myocardial damage process. However, there is a scarcity of studies correlating the histopathological (HISTO) changes with MPD in CCC. Purpose: We aimed at testing the hypothesis that MPD is more closely related to HISTO changes occurring in the endocardial layer in an experimental model of CCC in hamster. Methods: We investigated 23 female hamsters infected with 3.5 x 104 trypomastigote forms of T. cruzi, and 6 control non-infected. Animals underwent rest high-resolution 99mTc-Sestamibi SPECT myocardial perfusion scintigraphy, and rest transthoracic echocardiogram. The area of MPD was assessed through the calculation of polar maps by using Munich Heart(r) software. MPD was defined by areas with 99mTc-Sestamibi uptake <50% of the maximum pixel uptake value. After euthanasia, counting mononuclear cells for inflammation was performed by Weibel reticule in Hematoxylin-Eosin staining. Fibrosis was quantified by fraction area method using Red-Picrosirius staining. The analysis was topographically performed at three left ventricular myocardial wall layers: endocardial, mesocardial and epicardial. A total area of HISTO parameters was also computed, by summing up the respective areas of all myocardial layers. Results: Fourteen infected animals exhibited rest MPD (61%), and presented, in comparison to animals without MPD and to controls higher inflammation in total (1.09 +- 0.55, 0.93 +- 0.43, 0.41 +- 0.32, respectively; p = 0.03), endocardial (1.05 +- 0.50, 0.75 +- 0.44, 0.38 +- 0.22, respectively; p = 0.02), mesocardial (0.64 +- 0.44, 0.55 +- 0.33, 0.11 +- 0.08, respectively - p = 0.02) and epicardial layers (1.57 +- 0.97, 1.50 +- 0.73, 0.73 +- 0.89, respectively; p = 0.03). However, only the inflammation in endocardial layer presented positive correlation with individual values of MPD area (R = 0.55; p < 0.01). In addition, the total fibrosis area presented no difference between animal groups, but the endocardial layer presented a larger fibrosis area in the group with MPD (0.67 +- 0.18) compared to controls (0.45 +- 0.15; p = 0.03). Conclusion: Our results indicate a close relationship between MPD and HISTO changes in the endocardial layer of left ventricular myocardium, consistent with the notion that endocardial is the myocardial region more sensitive to the effects of myocardial ischemia in CCC. 109311 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Degree of Functional Independence in Patients Submitted to Cardiovascular Surgery After Discharge from Intensive Care PAULINE ELOISE MARIANI1, Marco Antonio Vinciprova Dall Agnese2, Grasiele do Amaral Martins2, Maria Antonieta Pereira de Moraes1 (1) Instituto de Cardiologia/Fundacao Universitaria de Cardiologia - IC/FUC; (2) Universidade Federal de Ciencias da Saude de Porto Alegre - UFCSPA Introduction: The functional capacity and degree of independence of patients undergoing cardiac surgery can be compromised by the length of stay in the Intensive Care Unit (ICU). Objective: To analyze the behavior of functional independence domains in patients undergoing cardiovascular surgery and its correlation with the length of stay in the ICU. Methods: Prospective cohort study, conducted with patients undergoing coronary artery bypass graft surgery and valvular surgery alone or in combination aged >=50 years. Outcomes: self-care, work ability, mobility and eliminations were evaluated using the Barthel Index and the Karnofsky Scale at hospital discharge and at 90 days by telephone. Results: Preliminary analysis of 172 surgical patients showed a predominance of men (70%), hypertensive (58%), dyslipidemic (43%), smokers (37%), aged 63 +- 11 years. Coronary artery bypass graft surgery was the most prevalent (57.6%), with cardiopulmonary bypass time of 82 +- 31 minutes. The length of stay in the ICU among all patients was 6 +- 2 days. The Barthel index showed that the functional impairment was lower at discharge (86%) and 90 days (64%), that is, they showed greater independence right after the intervention and after 3 months they were a little more dependent. The Karnofsky scale showed that the degree of dependence was similar at discharge and at 90 days after the intervention, 76% and 78% respectively. The most prevalent domains of functional status decline were self-care 11.4 +- 1.6 and mobility 15.8 +- 2.6. However, a very expressive inverse correlation was observed (r -0.152 and p < 0.05) with statistical significance, regarding the functional impairment after discharge from the ICU and at the 90 days of follow-up. Conclusion: Partial results indicate that there is a reduction in behavior in all domains of functional independence and an inverse correlation between the length of stay in the ICU and the functional impairment of these patients. Thus, long periods of stay in the intensive care unit seem to be inversely associated with the development of functional impairment in relation to an individual's basic daily activities. 109313 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Acute Ingestion of Nitrate-Rich Beetroot Juice Reduced Blood Pressure and Inhibited Platelet Aggregation in Healthy Male Individuals JEFFERSON FERNANDES EVANGELISTA1, Renata Alves1, Thaiane Lopes da Silva1, Juliana Silva Figueredo1, Cristiane Matsuura1 (1) Universidade do Estado do Rio de Janeiro Introduction: Beetroot is a functional food that has been gaining prominence due to its cardioprotective effects, in part attributed to its high nitrate content. Its effects are associated to the reduction of nitrate to nitric oxide, an important molecule involved in vascular homeostasis. Aims: To examine the effects of acute beetroot juice (BJ) ingestion on platelet aggregation, blood pressure (BP), and the expression of proteins involved in platelet activation in healthy adult men. Methods: Nine men (28 +- 6 yr old, 78 +- 8 kg, 1.77 +- 0.05 m), eutrophic and normotensive participated in the study. The experimental procedure consisted of only one visit in the morning. After 15 min of rest, BP was measured and blood was collected to measure platelet aggregation and protein expression by Western Blot. After that, the subjects ingested 500 mL of BJ (~400 mg of nitrate). After 2.5 h, a new measurement of BP was performed, as well as blood collection. Platelet aggregation was measured in washed platelets, platelet-rich plasma and whole blood using collagen (5 mg/mL) and ADP (10 mM) as agonists. Paired Student's t test was used to compare post-BJ conditions. Results: Acute BJ ingestion reduced ADP-induced platelet aggregation in platelet-rich plasma (-29%), but was not altered when induced by ADP and collagen in whole blood and washed platelets, as well as collagen in PRP. Regarding BP, we observed decreases in systolic and mean BP (-10% and -6%, respectively) after 2.5 h. Protein expression of phosphorylated protein kinase B (Tyr 437/434) was lower after BJ ingestion (-19%), but the expression of phosphorylated-endothelial nitric oxide synthase (Ser1177) and vasodilator-stimulated phosphoprotein were not altered. All results are shown in Table 1. Conclusion: Our findings indicate that the acute ingestion of nitrate-rich BJ can be a strategy for controlling BP and inhibiting platelet aggregation in healthy individuals, although the topic still lacks further investigation, including an understanding of the its mechanisms and its effects in populations with increased cardiovascular risk. 109320 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Arterial Stiffness: The Damage and Control MATHEUS TOSCANO PAFFER1, Pedro Toscano Paffer1, Rafaella Kelly Bello Wanderley1, Silvio Hock Paffer FIlho1 (1) Faculdade de Medicina de Olinda Introduction: Arterial stiffness is a new risk factor for cardiovascular diseases. It's relation to aging is well known, being a condition to the development of hypertension (HTN). Objective: Evaluate the arterial stiffness of elderly patients and its correlation to HTN. Methods: 31 very elderly patients were submitted for evaluation of the central blood pressure via a Mobil O'Graph of IEM device. Results: 31 very elderly patients were analyzed (older than 80 years old), from which 78.1% were females. At the average age of 85.8 (+-5.20), and with average BMI of 25.96 (+-4.32). With an average arterial systolic blood pressure of 143.06 mmHg (+-22.71) and the diastolic of 74.83 mmHg (+-9.30). The average central systolic blood pressure of 155.19 mmHg (+-32.88) and the diastolic of 80.96 mmHg (+-20.79). The average PWV (Pulse Wave Velocity) was 13.34 m/s (+-1.44). From the analyzed patients, 67.74% had altered their PWV values. Discussion The prevalence of HTN increases the aging and the occurrence of arterial stiffness plays an important role in this process. Even though this finding is not common, it shouldn't be considered a benign occurrence, because it's the main cause of HTN development. It's a condition prevalent in the elderly population, as observed in this cohort, but it can be reversed with the correct treatment for HTN. Conclusion: Arterial stiffness is a strong risk factor and important for the development of great cardiovascular diseases and its correlation with HTN is well known. Although the elderly population presents higher PWV rates, with an increase of arterial stiffness, it can be controlled and even reversed with optimized treatment of HTN. 109328 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Carotid Intima Thickness and Atherosclerotic Cardiovascular Disease Among Type 2 Diabetes Individuals: Results from the Brazilian Diabetes Study JOAQUIM DE PAULA BARRETO FONSECA ANTUNES DE OLIVEIRA 1, Nestor Martins2, Sheila Tatsumi Kimura-Medorima1, Sofia Vitte1, Thiago Quinaglia2, Barbara Assato1, Otavio Rizzi Coelho Filho2, Jose Roberto Matos-Souza2, Wilson Nadruz2, Andrei Carvalho Sposito1 (1) Laboratory of Atherosclerosis and Vascular Biology, Cardiology Division, Unicamp; (2) Cardiology Division, Unicamp Introduction: The accumulation of Apo-B containing lipoproteins in the subendothelial layer is an initiating step of atherosclerotic cardiovascular disease. In the carotid artery, this event is assessed noninvasively by arterial layers width measurement using B-mode ultrasound. Due to technical limitations, the intima-media thickness (C-IMT), and not the carotid intima (C-IT) width, where atherosclerosis manifests, has been pursued as a marker of disease with a negligible incremental value when compared with traditional risk factors prediction models. Objective: We sought to determine the prognostic value of C-IT for cardiovascular outcomes. Methods: This was a predefined analysis of the Brazilian Diabetes Study, an ongoing, single-center, prospective cohort of T2D individuals aged 30 years or more. Carotid ultrasound was performed by two trained physicians in each common carotid artery to obtain three manual measurements of far-wall C-IT, media (C-MT), and C-IMT. C-IMT above the 75th percentile for age, gender, and race group, and C-IT or C-MT above the sample's median were deemed as high. Cardiac CT was used to calculate the coronary artery calcium score, and a value above 0 Agatston was considered diagnostic of coronary artery disease (CAD). The primary outcome was major adverse cardiovascular events (MACEs) as a composite of death, myocardial infarction, stroke, myocardial revascularization, and limb amputation. Results: Among 402 individuals (Age: 58 + 7.6 years; 55% male; median T2D duration: 7.7 years) followed for 1676 days, 5 (3.1%) MACEs were reported in the low-IT, and 15 (10.1%) events were disclosed in the high-IT groups, with an HR of 3.11 (95%CI: 1.13, 8.58; p = 0.029). The prevalence of CAD was higher among high-IT than in low-IT group (58.4% vs 78.4%, p < 0.001), with an age-, and sex-adjusted OR of 2.29 (95%CI: 1.09, 4.85; p = 0.029). C-IMT and C-MT were not related to neither MACE nor CAD. Conclusions: C-IT, but not C-IMT nor C-MT, was related to incident MACEs and to coronary artery disease in T2D subjects. C-IT should thus be considered when assessing cardiovascular risk in T2D. 109345 Modality: E-Poster Young Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Indicators for Situational Screening of Rheumatic Fever in Brazil CAMILA POLIS BELLOTT1, Gustavo Tavares Lameiro da Costa1, Matheus dos Santos Silva de Oliveira1, Cristiane da Cruz Lamas1, Renato Cerceau1 (1) Instituto Nacional de Cardiologia - INC; (2) Fundacao Oswaldo Cruz - FIOCRUZ; (3) Universidade Federal do Rio de Janeiro - UFRJ Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD) once again stood out internationally in 2018 in the panel proposed by the World Health Organization (WHO) held in Assembly, which set a deadline for its control and eradication. A document that guides public policies for RF was organized. Contains indicators for situational tracking of the national and subnational context. The worldwide incidence of RF is 19/100.000. It is estimated 30.000 new cases/year. There are about 33 million people with RC in the world, resulting in 300.000 deaths annually. In order to assess Brazil's adherence to RF care, we applied the WHO tool. A search was carried out in public data and websites of medical societies. Data not found was requested in digital public services. It was possible to identify some national data, such as the number of cardiac surgeons (1.9/100.000 habitants), interventionists (0.46/100,000 habitants), echocardiography equipment (10572), cardiology services (40207). However, there is no mention of the value considered adequate. Overall mortality from RHD is low (0.16/100.000 habitants in 2014) but 3.9% of hospitalizations resulted in death, and 17% of those hospitalized for more than 90 days. As a comparison, in New Zealand, a reference country in the screening, control and treatment of RF, the annual mortality is 4.9/100,000 habitants. We were unable to quantify the acute cases and patients undergoing outpatient follow-up, there is only a record of hospitalization by international disease code involving RHD. It was impossible to count adherence to secondary prophylaxis, since there is no specific code for the application of Penicillin for RF. We saw that primary care is the most lacking in information. We highlight the absence of a code of procedure in the application of Penicillin for RF, non-accounting of acute cases and patients on secondary prophylaxis, recurrence of RF and mandatory notification of new cases. Is the incidence and prevalence of RF therefore falling? Or does the scarcity of data affect the measurement of the real epidemiological situation in Brazil? The Brazilian Society of Cardiology already highlights the importance of RF/RHD in our country. The socioeconomic impact of RHD must be reported to the government to include it in important public policies with the creation of a National Plan to combat and manage, training of health teams and guarantee of medication and adequate clinical follow-up to the patient. 109350 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Machine Learning for Predicting Readmission in the Coronary Care Unit DAYANNA DE OLIVEIRA QUINTANILHA PALMER1, Pedro Gemal Lanzieri1, Ronaldo Altenburg Odebrecht Curi Gismondi1, Flavio Luiz Seixas1, Guilherme Schittine Bezerra Lomba1 (1) Universidade Federal Fluminense (UFF) Electronic health records (EHRs) are a great opportunity for big data research and professionals from the Coronary Care Unit (CCU) can benefit to support clinical practice. This study aims to analyze epidemiological information from patients admitted to the CCU, the readmission impact on mortality, and the factors associated with readmission. We retrospectively analyzed patients 18 years or older, admitted to the Beth Israel Deaconess Medical Center, Boston, between 2008 and 2019. Data were accessed through the Medical Information Mart for Intensive Care, a public data bank. Patients without discharge data were excluded. Demographic data, vital signs, and lab were evaluated. Posteriorly, patients were divided into two groups: one of the patients who were readmitted and one of the patients who weren't. Factors associated with readmission were evaluated by statistical methods and machine learning. From an initial group of 53,150 patients, 8,015 were selected. The CCU mean period of stay was 2.8 days and the readmission rate was 7.42%. The mortality rate was 28.73% among those readmitted, while among those not readmitted, it was 18.61% (P-value < 0,001). The readmission rate was mainly influenced by the CCU length of stay, hospital length of stay, respiratory rate, creatinine, hematocrit, chloride, sodium, anion gap, temperature, and calcium. EHRs research can help define best practices and resource management. Machine learning was able to identify more relevant variables. Limitations include the need for longer analyzed periods and a broader data collection. 109362 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Cryoablation of Pulmonary Veins for the Treatment of Patients with Atrial Fibrillation After Coronavirus Infection (COVID-19) ALFREDO AURELIO MARINHO ROSA FILHO3, Lucas Brandao Cavalcante2, Alice Wanderley Rosa2, Briane Alcantara Vieira Pasini3, Alfredo Aurelio Marinho Rosa1, Edvaldo Xavier Ferreira Junior1 (1) Santa Casa de Misericordia de Maceio - SCMM/AL; (2) Centro Universitario Tiradentes - UNIT/AL; (3) Hospital Universitario Professor Alberto Antunes - HUPAA/UFAL Background: Coronavirus infection preferentially affects the upper airways and mainly the lung parenchyma, however, due to systemic infection, some patients have atrial fibrillation even in the absence of myocarditis or myocardial damage. Atrial fibrillation in most patients does not respond to drug treatment. Objective: To present the results of cryoablation for electrical isolation of pulmonary veins in patients with persistent atrial fibrillation after coronavirus infection. Material and methods: Between March 2020 and March 2022, 53 cases of cryoablation were performed for the treatment of atrial fibrillation, with 15% (8) of patients having atrial fibrillation after coronavirus infection. In all patients, atrial fibrillation did not respond to pharmacological therapy. In these patients, the echocardiogram showed a normal left atrium size, age ranged from 46 to 67 years with a mean of 59 years. The patients did not have structural heart disease or pulmonary sequelae of COVID-19. Of the 8 patients, 62.5% (5) were male and 37.5% (3) were female. All patients had a serological marker of previous infection assessed by IgG serology. Patients were referred to the electrophysiology laboratory, under venous sedation, submitted to transseptal puncture and then an angiography was performed to locate the pulmonary veins and introduction of a balloon catheter where an application of 04 minutes in each pulmonary vein was performed, temperature ranged -51 to -62 with an average of -55 degrees Celsius. In the trans and postoperative period, no complications were recorded. Results: In 100% (8) of the patients, all four pulmonary veins were isolated. There were no complications such as esophageal and/or phrenic nerve injuries and all patients returned to sinus rhythm. Conclusion: The disease caused by the coronavirus can lead to serious cardiac complications, such as uncontrolled atrial fibrillation, refractory to optimized drug treatment. In this sample, the experience of Cryoablation of pulmonary veins proved to be a safe alternative for patients with atrial fibrillation after coronavirus infection. 109380 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Cardiometabolic Risk Factors Among Nursing Students: Just Knowledge Does not Chance Behavior! YASMINN BENEVIDES ADBA1, Anne Caroline Lisboa Marinho2, Andressa Teoli Nunciaroni1, Bruna Ribeiro Almeida Magalhaes1, Caio Victor Chagas das Virgens1, Clauanny Caroliny Bicego Reis Nogueira1, Debora Novais Lopes1, Judson Vieira de Carvalho Pereira1, Juliana Resende Correa Lima1, Luan Wesley Marques Maximo3, Renata Flavia Abreu da Silva1, Yasmin Rocha de Almeida1 (1) Federal University of the State of Rio de Janeiro - UNIRIO; (2) Federal University of Rio Grande do Norte - UFRN; (3) State University of Piaui - UESPI Introduction: In the context of high prevalence of Cardiovascular diseases (CVD), conditions faced by nursing students such as high curricular workload, stress, lack of time, long commute to university, access to food with low nutritional value, deserve attention in view of primary prevention. Objectives: To identify the cardiometabolic risk factors and its knowledge among nursing students. Methods: Cross-sectional, descriptive and quantitative study. An online self-instructional questionnaire was used for sociodemographic characterization and identification of cardiometabolic risk factors. The knowledge of cardiovascular risk was assessed from five statements about: modifiable risk factors, prevention of CVD, protective behaviors implementation and the contact way with the topic. Nursing Students from a Federal University were enrolled. Data collection occurred from September, 2021 to March, 2022. Data was analyzed through RStudio Software. The study was approved by the local Ethical Committee. Results: The study included 117 nursing students with 24.5(+-5.7) years on average. Most(75.4%) were female, single(92.9%), with family income between two and four minimum wages*(59.6%), living with relatives(87.5%). Most of the students were attending 5th and 6th semester(22% and 20%, respectively). Regarding the time spent commuting to the university, 63.4% reported between 30 to 120 minutes. The risk factors identified in the sample are reported on Table 1. 74.6% declared CVD family history. Results relating to knowledge are presented on Figure1. *1 minimum wage = US$253.35. Conclusions: The study shows cardiometabolic risk factors among undergraduate nursing students, even when knowledge about the topic is reported. Knowledge does not mean implementing protective behaviors. 109410 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSIOTHERAPY Predictors of Functional Status in the Immediate Postoperative Period of Cardiovascular Surgery VICTORIA MARIA GARCIA DE MEDEIROS1, Jessica Goncalves de Lima1, Fernando Gomes de Jesus1, Ana Gabriella Arena de Sa,1, Thaisa Sarmento dos Santos1, Cristianne Rafael Campos,1, Lucas Araujo de Carvalho1, Marcus Vinicius de Souza Amaral1, Juliana Rega1, Claudia Rosa1, Mauro Felippe Felix Mediano1, Luiz Fernando Rodrigues Junior.1 (1) National Institute of Cardiology Introduction: Patients in the postoperative period (PO) of cardiovascular surgery (CS) may have reduced functional status during hospitalization. However, little has been studied regarding preoperative, intraoperative and PO factors that may be related to better functionality at the time of discharge from the intensive care unit (ICU). Objective: To identify pre, intra and PO predictors of functional status of patients under PO of CS. Methods: Retrospective cross-sectional study. Data from 614 patients was obtained from the Physiotherapy Service database (stored in REDCap) and reviewed in medical records of the Instituto Nacional de Cardiologia (Rio de Janeiro-RJ), from October/2018 to March/2020. Preoperative variables such as age, sex, body mass index (BMI) and comorbidities were collected. Intraoperative variables were: type/complexity of surgery, fluid balance, time on cardiopulmonary bypass, time of aortic clamping, and surgical complications. The variables evaluated in the PO were: level of consciousness, pain on admission, fluid balance, imaging tests, blood gases, laboratory tests, mechanical ventilation and pulmonary function before and after extubation, peripheral muscle strength, extubation attempts and failures. Functional status was quantified at ICU discharge using Functional Status Score for the ICU (FSSICU). The univariate and multivariate linear regression model (P < 0.05 considered significant) was used to verify the association of possible predictors of functional status. Results: The PO variable: obesity (BMI >= 30 kg.m-2; b = -2.8; CI: -5.4 -0.3; P = 0.026) was negatively associated with functional status in the ICU; while the postoperative variables: pain on admission (b = 11.2; CI: 1.8-20.5 P = 0.02) and peripheral muscle strength at discharge (b = 0.3; CI: 0.2-0.4; P = 0.001) were directly and independently associated with functional status at discharge; Furthermore, muscle strength at the time of extubation were directly and independently associated with strength at discharge (b = 11.1; CI: 0.1-0.2; P = 0.007). Conclusion: Pain intensity on admission and peripheral muscle strength at ICU discharge predict functional status at discharge, while muscle strength at the time of extubation was evidenced as an independent predictor of muscle strength at discharge, and a suggestive intervention target for preventing functional status loss in adults submitted to cardiac surgery. 109426 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Impact of Small Stent Diameter in Patients with St Elevation Myocardial Infarction GUILHERME PINHEIRO MACHADO1, Gustavo Neves de Araujo3, Arthur Cabareira Baptista4, Mariana Rabolini4, Luiza Atanazio4, Alan Pagnoncelli1, Angelo Chies2, Wagner Azevedo2, Rodrigo Wainstein1, Marco Vugman Wainstein1 (1) Hospital de Clinicas de Porto Alegre (HCPA); (2) Universidade Federal do Rio Grande do Sul (UFRGS); (3) Imperial Hospital de Caridade; (4) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) Introduction: In patients submitted to elective percutaneous coronary intervention (PCI), treatment with small stents diameters (SD) has been associated with worse outcomes. However, the impact of small SD on outcomes in patients with acute myocardial infarction in scarce. Methods: This was a prospective cohort study that included patients with STEMI submitted to pPCI admitted to a tertiary university hospital between April 2011 and December 2021. Patients were categorized into groups based on SD. Small SD was considered <2.50 mm. Patients who underwent implantation of multiple stents were assigned to the study group according to the smallest stent size used. The primary clinical outcome was major adverse cardiovascular events (MACE) defined by death, in-hospital MI, stroke, and stent thrombosis and target vessel revascularization. Secondary outcomes included MACE and each individual outcome at in-hospital, 30 days and long-term period. Results: From 1458 Patients admitted with STEMI in the study period, 1238 were included and 468 (34.4%) were women. Mean age was 63.4 +- 12.8 years in small stent diameter vs 60.4 +- 11.7 years (p = 0.009). Patients with small SD had a higher prevalence of diabetes (36.9 x 25.3%, p = 0.003) and previous acute myocardial infarction 11 x 17%, p = 0.04). In multivariate analysis, stent diameter <2.5 mm remained independent predictor of MACE (odds ratio [OR] 1.6 95% confidence interval [95% CI] 1.08-2.42; p = 0.018); mortality (OR = 1.78, 95%CI = 1.092-2.878; p = 0.018, and target vessel revascularization (OR = 1.963; 95%CI = 1.019-3.612; p = 0.036). Conclusion: In this prospective cohort study of patients with STEMI treated with PCI, a small stent diameter <2.5 mm was associated with increased rates of MACE, mortality and target vessel revascularization. 109427 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Resistance to Obesity Promotes Metabolic Alterations and Cardiac Hypertrophy Without Changes in the Reactive Oxigen Species JANETE CORREA CARDOSO1, Amanda Rangel Madureira1, Vinicius Valois Pereira Martins1, Ramon dos Santos1, Suellem Torezani Sales1, Ana Paula Lima-Leopoldo1, Andre Soares Leopoldo1 (1) Universidade Federal do Espirito Santo (Ufes) Resistance to Obesity is associated with the complex interaction of stringent and environmental factors, conferring the ability to gain mass gain and body fat deposition, even when eating high-calorie diets. Considering that there are numerous gaps in the literature on the metabolic processes that explain Resistance to Obesity, specifically in relation to oxidative stress, the purpose of the study was to investigate whether obesity-resistant rats develop elevated reactive oxygen species in cardiac tissue. Wistar rats (n = 71), aged 30 days, were initially randomized into two groups: a)Standard diet (n = 35) and b)High-fat diet (n = 36). The experimental protocol consisted of two moments: obesity induction (4 weeks) and characterization of resistance to obesity (10 weeks). After obesity detection, the animals were redistributed into three groups: Control (C), Obese (Ob) and Obesity-Resistant (ROb). Was analyzed: Nutritional profile, metabolic changes, cardiac mass and Oxidative stress. The comparison of the experimental groups was performed using ANOVA, complemented with Tukey's multiple comparisons test. The level of significance considered was 5%. Body mass showed a significant difference between the standard diet and high-fat diet groups in the 4th week of the experimental protocol, characterizing obesity. In the 4th week, after the characterization of Resistance to Obesity, there was a significant difference in body mass between groups C, Ob and ROb. Ob and ROb groups showed a significant increase in caloric intake (p < .001; p = .0005) in relation to the C. Ob group showed a significant increase in final body mass (p < .0001; p = .03), in retroperitoneal fat pad (p.0001; p = .006), sum of corporal fat deposits (p < .0001; p = .02) and in reactive oxygen species (p = .001; p = .0006), in relation to groups C and Rob. The area under the glycemic curve (p = .02), insulin resistance index (HOMA-IR) (p = .02) and basal glucose (p = .01) were elevated in the Ob group in relation to the C. Resistance to Obesity also promoted an increase in HOMA-IR when compared to C. Total cardiac mass (p = .0004 and;p = .01), right (p < .0001; p = .002) and left ventricles (p = 0.002; p = 0.03) the cross-sectional area (p < .0001; p < .0001) and cholesterol levels (p = .0001; p = .001) in were significantly elevated in the Ob and Rob groups compared to the C group. In conclusion, Resistance to Obesity promotes metabolic alterations and cardiac hypertrophy without changes in reactive oxygen species. 109458 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Copper Overload Causes a Reduction of Vascular Reactivity in Diabetic Rats KAROLINI ZUQUI NUNES1, Dalton Valentim Vassallo1, Julia Antonietta Dantas da Silva1 (1) Universidade Federal do Espirito Santo - UFES Introduction: It is a known fact that diabetes mellitus is associated with several cardiovascular abnormalities such as increased arterial stiffness and endothelial dysfunction. In addition to these changes, enhanced plasma copper concentration is also characteristic in individuals with diabetes. Although there are theories that the increase in plasma copper concentration and the development of cardiovascular problems are related, to date the mechanisms that explain this correlation are still unclear. Objective: The present study seeks to understand the effects of chronic copper overload on vascular reactivity in isolated segments of the thoracic aorta of diabetic rats. Methodology: This is an experimental study, in which about 44 12-week-old Wistar rats were used, weighing approximately 200g, obtained from the central vivarium of Federal University of Espirito Santo (UFES). The experimental protocols were approved by the university's animal use ethics committee No 22/2019. The animals were divided into four experimental groups: Control (CT); Copper (Cu); Diabetes Mellitus (DM); Diabetes Mellitus + Copper (DM+Cu). Type 1 diabetes was induced via a single injection of streptozotocin 50 mg/kg/i.v., and the animals were treated with twice the recommended daily dose of copper (1.8 mg/kg). They were then killed after 30 days of treatment, and the thoracic aorta was removed for vascular reactivity experiments. Statistical tests, one-way and two-way ANOVA were used to examine the outcomes. Results: The main findings show a reduction in vascular reactivity in the DM+Cu group: Using an inhibitor of nitric oxide synthase (L-NAME), an increased bioavailability of nitric oxide was suggested, explaining the vasodilation; employing an inhibitor of NADPH oxidase activity (Apocynin) and an enzyme that degrades hydrogen peroxide (Catalase) we showed the participation of hydrogen peroxide as a vasodilator factor; the potassium channels blockade (tetraethylammonium) suggests the participation of the channels for potassium as vasodilators; and the use of selective angiotensin II AT1 receptor antagonists (Losartan) suggests that angiotensin II could be acting on AT2 receptors as vasodilators. Conclusion: Copper overload in diabetic rats causes a reduction of the aorta vascular reactivity of, which can be explained by the action of nitric oxide, hydrogen peroxide, and potassium channels, which are potential vasodilators, thus explaining the mechanism of our main discovery. 109470 Modality: E-Poster Young Researcher - Non-case Report Category: PSYCHOLOGY Quality of Life and Mental Disorders Profile Among a General Population of Pre-Hypertensive and Hypertensive Patients JOAO GABRIEL REGA DO NASCIMENTO VALLAPERDE1, Bianca Botelho Viegas1, Fernanda Oliveira de Carvalho Carlos1, Victor Margallo1, Vitor de Melo Nolasco1, Joao Gabriel Bezerra da Silva1, Bianca Zattar de Mello Barreto1, Marcus Vinicius Serejo Borges Vale da Silva1, Daniela Fiuza2, Karine Guimaraes2 (1) Universidade Federal do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho - ProHArt; (2) Universidade Estacio de Sa - UNESA Introduction: Symptoms of depression and anxiety may interfere in the quality of life of individuals diagnosed with hypertension. Objectives: To investigate the association between anxiety, depression and quality of life among pre-hypertensive and hypertensive patients. Materials and methods: A cross-sectional study including 89 pre-hypertensive (n = 15) and hypertensive (n = 74) participants. All of them were submitted to a standard protocol with collection of sociodemographic data, cardiovascular risk factors, BP measurement and mental health evaluation. For depression symptoms, it was used the Patient Health Questionnaire-9 (moderate/severe depression >=10 points); for anxiety, the Generalized Anxiety Disorder Assessment-7 (moderate/severe anxiety >=10 points); for quality of life, the World Health Organization Quality of Life instrument. Bivariate analyses were performed to compare participants' characteristics according to the presence of anxiety, depression, and quality of life. Logistic regression assessed the main variables independently associated with moderate/severe anxiety and depression and reduced quality of life. Results: The average age was 50.2 +- 11.2 years old and 52.8% of the participants were female. Blacks and browns were the majority (53.9%). 21% of the participants have low education (Elementary School) and 64% have family income <=3 minimum wages. Sedentary lifestyle (43.8%) and dyslipidemia (47.2%) were the most common risk factors among this population. Moderate/severe depression was found in 46.6% of the participants and moderate/severe anxiety in 43.8%, with no differences between men and women. The mean score of quality of life was 87 [63-111]. The presence of moderate/severe depression, moderate/severe anxiety and worse quality of life was not associated with sociodemographic conditions nor traditional CV risk factors, but they were associated with each other. Moderate/severe depression increased elevenfold the risk of worse quality of life (OR = 10.9; IC95% 2.81-41.65; p < 0.001). Moderate/severe anxiety (OR = 6.41; IC 95%; p < 0.004) and worse quality of life (OR = 11.19; IC 95%; p < 0.001) were independently associated with moderate/severe depression. The independent variable associated with moderate/severe anxiety was the presence of moderate/severe depression (OR = 6.37; IC 95%; p < 0.004). Conclusion: The presence of depression and anxiety symptoms were associated with each other and with worse quality of life of individuals evaluated. 109473 Modality: E-Poster Young Researcher - Non-case Report Category: DYSLIPIDEMIA Functional Aspects of the HDL Particle: A Comparative Study between Patients with Refractory Angina, Non-Limiting Angina, and Healthy Individuals SARAH FAGUNDES GROBE1, Mauricio Tavares1, Thauany Tavoni1, Pedro Gabriel Senger Braga1, Raul Cavalcante Maranhao1, Luis Henrique Wolff Gowdak1 (1) Instituto do Coracao da Faculdade de Medicina da USP - InCor HCFMUSP Introduction: HDL particle plays an important role in atherosclerosis for its complex metabolism and relationship with other pro-atherogenic lipoproteins. Patients with refractory angina (RA) usually presente advanced atherosclerosis of the coronary arteries. So far, no biochemical markers have been found to explain the greater atherosclerotic involvement in patients with RA compared with patients with non-limiting angina (NLA). Objective: To compare the activity of paraoxonase 1 (PON1) and the HDL particle diameter in patients with RA or NLA with healthy individuals (HI). Methods: 35 patients (15 RA and 20 NLA) and 20 HI were included. Plasmatic concentrations of lipids were determined using commercial kits and ApoA-1 and ApoB by the turbidimetric method. The HDL particle diameter was measured by light scattering method and PON1 activity by the spectrophotometric method. One-way ANOVA was used for statistical analysis, and a P-value < 0.05 was considered statistically significant. Results: There were no differences in age, sex, and body-mass index between groups. The lipid profile was similar between groups, except for higher levels of HDL-cholesterol and ApoA-1 in HI (see Table). There were no differences in ApoB concentrations, HDL particle size, and PON1 activity. Conclusion: As expected, patients with coronary atherosclerosis had lower ApoA-1 and HDL-cholesterol levels than HI. However, the HDL particle size and the PON-1 activity were similar among patients with RA or NLA. The search for markers of plasma lipid metabolism able to discriminate between patients with RA and NLA is of interest. They may mirror metabolic alterations related to the genesis of RA and become therapeutic targets. 109481 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Ablation of Anomalous Pathways Manifested in the Mitral Annulus Through Transradial Access with Early Hospital Discharge Due to the COVID-19 Pandemic ALFREDO AURELIO MARINHO ROSA FILHO3, Lucas Brandao Cavalcante2, Alice Wanderley Rosa2, Briane Alcantara Vieira Pasini3, Dandara Dias Gomes Cunha3, Alfredo Aurelio Marinho Rosa1, Edvaldo Ferreira Xavier Junior1 (1) Santa Casa de Misericordia de Maceio - SCMM/AL; (2) Centro Universitario Tiradentes - UNIT/AL; (3) Hospital Universitario Professor Alberto Antunes - HUPAA/UFAL Ablation of manifest anomalous pathways in the mitral annulus through transradial access with early hospital discharge due to the COVID-19 pandemic. Introduction: Ablation of anomalous pathways on the left or in the mitral annulus can be approached by transseptal puncture, by retrograde aorta approach or through the transradial approach. Due to the shortage of infirmary beds during the Covid-19 pandemic, we chose to perform transradially due to early hospital discharge. Material and methods: Between January 1998 and December 2021, 3,535 catheter ablations were performed. In 29,9% (1059) patients were treated for manifest anomalous pathways, of these 54.3% (575) were male, with ages ranging from 03 to 75 years and a mean of 31.24 years, success was obtained in 94, 9% (1005) of cases. Our service had previously performed 16 cases of transradial ablation. During the COVID-19 pandemic and the difficulty for the hospitalization of patients, between May 2020 and July 2021, 8 cases of ablation of manifest anomalous pathways manifested in the mitral annulus were performed, 62,5% (5) were anterolateral and 37,5%(3) Left postero-septal. 62,5% (5) patients were male and the age ranged from 24 years to 56 years with a mean of 40 years. The approach was made through the right radial artery, under local anesthesia, the patient was submitted to venous sedation, introduction of a 7Fr introducer and placement of only the exploratory catheter. Mapping performed always during sinus rhythm and after ablation performed tests with IV adenosine. The catheter was removed and a local pneumatic dressing was applied for 2 hours and replaced with a conventional dressing for 24 hours. All patients were selected after performing Doppler imaging of the radial and ulnar arteries. COVID-19 test were negative for all patients. Results: In the 8 patients ablation was successful (100%), the procedure time ranged from 40 minutes to 80 minutes with an average of 55 minutes. No complications were recorded during or after the procedures, all patients were discharged from hospital 3 hours after the intervention. At outpatient follow-up, all patients are asymptomatic and have an ECG without ventricular pre-excitation. Conclusion: Faced with the COVID-19 pandemic and lack of hospital beds for elective admissions of patients with left manifest anomalous pathways, the transradial approach was a safe option providing early hospital discharge. 109502 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The COVID-19 Pandemic Impact on Stroke Notification in Brazil: An Epidemiological Study DEBORAH ESTEVES CARVALHO1, Deborah Esteves Carvalho1, Anna Laura Lima Larcipretti2, Aline Dias Bedetti2, Julia Regina Assis da Rosa2, Barbara Alves de Abreu Rocha2, Leonardo Brandao Barreto3 (1) Universidade Tiradentes, Aracaju, Brasil (UNIT); (2) Escola de Medicina, Universidade Federal de Ouro Preto, Ouro Preto, Brasil (UFOP); (3) Departamento de Clinica Pediatrica e Adulto, Universidade Federal de Ouro Preto, Ouro Preto, Brasil (UFOP) Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has placed a drastic strain on healthcare services, requiring the reallocation of resources, and possibly affecting the quality of stroke monitoring and care. Objective: This is an epidemiological, descriptive, and retrospective study to analyze the profile of stroke in Brazil from January 2018 to December 2021. In addition, we aim to investigate the impact of the pandemic on stroke monitoring, including the possible reasons for the underreporting of cases. Methods: The results were obtained by collecting data from the SUS Hospital Information System (SIH/SUS). Also, a review of the literature on this topic was performed, using the Pubmed database. Results: Stroke is one of the main causes of mortality and morbidity worldwide. Although an increased number of stroke cases was expected due to cardiovascular events caused by the SARS-CoV-2 infection, the data show otherwise. Between 2018 and 2019, there was an increase of 6,116 in the number of cases. In contrast, a drop of 12,889 and 5,490 in the number of cases between the years 2019 and 2020, and 2020 and 2021, respectively, was observed. A significant decrease in the number of cases was observed in the Northeast region and in the elderly population. The literature describes many possible reasons for the underreporting. The most present hypothesis was fear of infection by the virus, which may have prevented many from seeking emergency medical care, impacting directly on the notification of stroke cases. Moreover, studies indicate that social distancing makes the recognition of stroke signs more difficult since the latter is facilitated by person-to-person interaction. Also, the pandemic requires the reallocation of healthcare resources to be used for COVID-19 care, it can create gaps in stroke care, affecting its quality. Conclusions: Thus, the decreased number of stroke cases observed between 2019 and 2021 may be a result of underreporting, which could be a direct impact of the COVID-19 pandemic on stroke care and monitoring. 109510 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Contact Force Sensing Technology in Atrial Fibrillation Catheter Ablation: A Prospective, Single-Center, Cohort Study GABRIEL ODOZYNSKI1, Isabella Bianco3, Helcio G. Nascimento1, Andrei Lewandowski1, Mauricio L. Spessatto1, Clovis Froemming1, Grazyelle Damasceno1, Alexander Dal Forno1, Andre d'Avila1 (1) Hospital de Cardiologia SOS Cardio; (2) Instituto de Cardiologia de Santa Catarina; (3) Universidade do Sul de Santa Catarina Introduction: The use of contact force (CF) sensing catheters aims to provide safety and efficacy to atrial fibrillation (AF) ablation by permanent pulmonary veins electrical isolation. Objective and Method: This study sought to evaluate the AF catheter ablation outcomes (recurrence rate and adverse events) in a single-center, prospective cohort of 380 patients underwent to first-ever procedure using CF sensing technology. Data were analyzed based on digital AF ablation database/SysCardio(r). Recurrence was defined as any atrial arrhythmia documented - episodes of 30s or longer after blanking period (90 days). Results: Of 380 enrolled patients, 290 patients had paroxysmal AF (<=7 days-PAF) and 90 patients persistent AF (>7 day <=1 year-AF-Per). The mean age was 63 +- 11 and 67 +- 10 years, respectively. 68% and 80% of patients were men in the PAF and AF-Per groups. There was no difference among PAF and AF-Per groups regarding, hypertension and diabetes mellitus, coronary artery disease and previous stroke (16 patients). The CHA2DS2-VASc was 1.8 +- 1.4 vs 2 +- 1.5 in PAF and AF-Per, respectively. After the first procedure, 44 patients (15%) and 22 (24%) had recurrence in PAF and AF-Per groups (Fig.1). Considering a sequential redo procedure, these rates decrease to 5 and 8% in PAF and AF-Per, respectively. There were 15 minor primary adverse events from 427 procedures (7 inguinal hematomas, 6 pseudoaneurysms [1 surgical] and 2 pericardial effusions, no surgical drainage need). There were no major complications. There were no deaths related to the procedure. Conclusion: Initial outcomes using CF sensing technology catheter to AF ablation demonstrate a cumulative recurrence rate of 5% and 8% in patients with PAF and FAP-Per. The procedure is safe, no major adverse events were recorded in our study. 109527 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY The Cone Procedure to Ebstein's Anomaly Repair: Clinical and Echocardiographic Outcomes NATALIA ALBERTIN DOS SANTOS1, Jose Cicero Stocco Guilhen1, Omar Alonzo Pozo Ibanez1, Vivian De Biase1, Renata Burini Chaccur1, Jaime da Conceicao Padeiro Junior1, Luciana Fonseca Martins1, Wanda Teixeira Moreira do Nascimento1, Wagner Knoblauch Santos1, Maria de los Angeles Garcia Andrade1, Daniela Lago Kreuzig1, Simone Rolim Fernandes Fontes Pedra1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Ebstein's anomaly occurs due to failure in the delamination of the septal and posterior leaflets with apical displacement of the functional annulus, dilatation of the atrialized portion of the right ventricle, thinning of the free wall, dilatation of the true annulus and redundant anterior leaflet with multiple fenestrations. The "Cone" reconstruction of the tricuspid valve, described by Silva et al, results in complete coaptation of the valves with excellent results in the medium and long term. Objectives: In this study, clinical and echocardiographic data of patients undergoing surgical repair using this technique was reviewed. Methods: Pre and post-operative (PO) records and echocardiograms of 8 patients operated on from 2018 to 2022 were reviewed. Results: The median age of the group was 22.5 (2 to 42 years). In the pre-operative 3 patients had Wolf-Parkinson-White ventricular pre-excitation and 6 had atrial septal defect associated, 6 had moderate to severe dyspenia, with only one being cyanotic. All had severe tricuspid regurgitation (TI) and 6 had moderate to severe right ventricular dilatation. In the immediate PO, moderate TI was detected in 2 and mild in 6. In 1 patient, Glenn anastomosis was added to the Cone procedure due to hemodynamic instability and hypoxemia immediately after bypass. In the post-operative follow-up time, median of 11.5 months, all patients were asymptomatic and TI increased from mild to moderate in only one case. One patient required pacemaker implantation due to complete atrioventricular block. Conclusion: In this small cohort, the Cone procedure resulted in significant improvement of the tricuspid regurgitation, no mortality and low morbidity with significant improvement of the clinical status. 109533 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Epidemiological Profile of Chronic Rheumatic Heart Disease Hospitalizations in the North Region in Brazil between 2011 and 2021 LEONARDO LEAO BARROS1, Ludmila Oliveira dos Reis2, Mariana Lassance Maya Palheta1, Maria Luiza do Socorro Alves Lucas3, Juliana de Sousa Tavares1 (1) Universidade do Estado do Para - UEPA; (2) Universidade Federal do Para - UFPA; (3) Centro Universitario do Estado do Para - CESUPA Introduction: The chronic rheumatic heart disease describes a group of heart diseases that can occur as a result of rheumatic fever. It is the most common cause of heart failure in children and young adults. In Brazil, these disorders generate high costs for the health system, with large number of hospitalizations resulting from this pathology. Besides, in the North region there is a high prevalence of this comorbidity. Objective: To evaluate and analyze the epidemiological profile of patients undergoing hospitalization for chronic rheumatic heart disease, in addition to determining their incidence and prevalence, in the period from 2011 to 2021 in Northern Brazil. Method: This research is a cross-sectional, analytical, and retrospective study, with observation of the period from 01/2011 to 12/2021. The materials used as a source were collected by the informatics department of the Brazilian Unified Health System on hospitalizations for rheumatic heart disease in the North region of Brazil and three variables were analyzed: age group, sex and race. Results: There were a total of 3.891 hospitalizations. The male population corresponded to 47,87% (1.863) of the hospitalizations, the female population corresponded to 52,12% (2.028). The races: brown, "no information", white, black, yellow and indigenous, corresponded respectively to: 60,62% (2.359), 30,40% (1.183), 5,98% (233), 2,18% (85), 0,56% (22) and 0,23% (9). For age groups, the following ranges in years: "< 19", "20 to 59" and "60 and +", corresponded respectively to: 12,02% (468), 64,53% (2511) and 23,43% (912) of the hospitalized population. Conclusion: Rheumatic heart disease (RHD) is a condition with a significantly larger prevalence in women. Different studies show the ratio to be 2:1. In this study, women indeed corresponded to a larger number of hospitalizations (52,12%). But, the ratio found was only 1,08:1. No relation between race and RHD was found in studies. The higher prevalence in the brown race (60,62%) may be a reflection of the ethnic distribution of the region. RHD has a higher prevalence in the 25 to 45 years range. This is consonant with the findings of this study, which showed that the adult population with age between 20 and 59 corresponded to 64,53%. 109554 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Autonomic Dysfunction Post-COVID-19 in Obese: Cross-Sectional Study ALICE PEREIRA DUQUE1, Luiz Fernando Rodrigues Junior1, Humberto Batista de Macedo Junior1, Daniel Arthur Barata Kasal1 (1) Education and Research Department. National Institute of Cardiology. Rio de Janeiro, RJ, Brazil Introduction/Objective: Autonomic dysfunction, a commonly underdiagnosed clinical entity with important cardiovascular implications, can occur in post-COVID-19 Syndrome. However, the entire impact of obesity on this clinical entity is still unknown. Thus, we aimed to assess if obesity can be a predictor of autonomic dysfunction in post-COVID-19 patients. Methods: Cross-sectional study recruited employees from a public hospital in Rio de Janeiro. Inclusion criteria: age >= 18 years and previous diagnosis of COVID-19. Exclusion criteria: physical inability to perform the autonomic test. Clinical, anthropometric and sociodemographic variables were collected. Volunteers were asked about the presence of cardiovascular symptoms (lipothymia, syncope, palpitations, dyspnea or chest pain) after COVID-19, and classified according to body mass index (BMI) in non-obese and obese (BMI < 30 and >=30 Kg/m2, respectively). Autonomic dysfunction was defined as the presence of orthostatic hypotension (OHYPO) and/or orthostatic hypertension (OHYPER). Systolic (SBP) and diastolic (DBP) blood pressure variation was evaluated after 15min of rest followed by 3min of orthostasis. Variations of SBP >= 10 mmHg and DBP >= 5 mmHg were considered as alterations. The association between variables was assessed using Fisher's exact test and logistic regression adjusted by sex, age and medications that may influence autonomic function. P < 0.05 was considered significant. Results: In 55 volunteers evaluated, none required hospitalization and only 10.9% (N = 6) had post-COVID-19 symptoms. The time between COVID-19 diagnosis and the evaluation was 405 [380-421]days. In total, 87.3% (N = 48) had autonomic dysfunction. Of these, 76.4% (N = 42) had OHYPER and 20% (N = 11) had OHYPO. In common to both groups, 9.1% (N = 5) had both alterations. Non-obese represent 82.5% (N = 33) of the participants who had OHYPER, against 17.5% (N = 7) obese volunteers (P = 0.001). Obese individuals represent 32% (N = 17) of our sample. Of the volunteers who had OHYPO, 72.7% (N = 8) were obese, against only 27.3% (N = 3) non-obese (P = 0.002). Obesity exhibited a positive association with the occurrence of post-COVID-19 OHYPO (OR = 12.4; P = 0.009). Conclusion: Obesity increases in 12 time-fold the risk of developing post-COVID-19 OHYPO. The high prevalence of post-COVID-19 OHYPO in obese individuals occurs regardless of the presence of symptoms and the infection severity, suggesting that obesity could be a predictor of post-COVID-19 autonomic dysfunction. 109640 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Cardiopulmonary Resuscitation Procedures Addressed Through Telesimulation to Health Professionals GISELLE OLIVEIRA AZEREDO1, Renata Flavia Abreu da Silva1, Andressa Teoli Nunciaroni1, Vanessa de Almeida Ferreira Correa1 (1) UNIVERSIDADE FEDERAL DO ESTADO DO RIO DE JANEIRO (UNIRIO) Introduction: Training in Cardiopulmonary Resuscitation through Telesimulation is challenging, due to its theoretical-practical peculiarity. However, gaps in the knowledge of health professionals can be filled through this remote education strategy. It is worth mentioning the actions described in the Cardiopulmonary Resuscitation protocol, which, if they have any problems in their compliance, can negatively influence the patient's clinical outcome. Objective: To analyze Cardiopulmonary Resuscitation procedures addressed through Telesimulation to health professionals. Methods: Descriptive, cross-sectional, retrospective and quantitative study. We included secondary data from a remote course database with the telesimulation strategy and application of pre and post-tests instruments. The questionnaires items were grouped into four thematic areas: Identification and management; analysis of cardiac rhythms; medication administration; leadership. Participants were invited to provide their data. Descriptive and inferential statistics were used for data analysis. The study was approved by the Research Ethics Committee, with number: 4,945,123/2021. Results: 35 groups were formed with the participation of 227 health professionals. The pre-test, which corresponded to a situational diagnosis, showed that the leadership action had the highest number of hits, with 93 (96.8%), 47 (97.0%) and 70 (90.9%) and the action referring to the administration of epinephrine had the highest number of errors, with 11 (11.4%), 5 (9.20%) and 13 (16.8%) correct answers. The answers corresponded to the questionnaires applied in the three telesimulated scenarios, namely, hospital scenario (n = 96), psychiatric scenario (n = 54) and emergency scenario (n = 77). However, there was a progressive increase in correct answers of 47% and 69% between pre-test and post-test 1, respectively. In addition to the significant increase in their overall hit mean from 4.66 (1.67) to 6.85 (1.69), respectively (p < 0.0001). As for post-tests 1 and 2, there was an increase from 69% to 80%, and an overall average of correct answers from 6.85 (1.69) to 8.04 (1.55), respectively (p < 0.0003). Conclusion: The Telesimulation method, via remote course, seems to contribute to Cardiopulmonary Resuscitation procedures learning, considering the number of correct answers in the sample and the contexts studied. 109654 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Increased Qt Dispersion in Depressed Patients Without Cardiovascular Disease: Systematic Review and Meta-Analysis VITHORIA VIDOTTI NEVES1, Julio Cesar Tolentino Junior1, Sergio Luis Schmidt1, Alan Marques Joaquim1, Vithoria Vidotti Neves1 (1) Hospital Universitario Gaffree e Guinle Background: Depression is linked to increased cardiac mortality risk. Dispersion of QT interval is an indirect electrocardiography (ECG) expression of ventricular repolarization heterogeneity. Increased QT dispersion is related to a higher risk of arrhythmias and sudden death. Therefore, depression may be associated with increased QT dispersion even in cardiac-healthy patients. Objective: We conducted a meta-analysis to investigate whether QT dispersion could be increased in depressed patients without cardiovascular disease. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed by two independent reviewers. A systematic search of MEDLINE and EMBASE from 1990 to 2022 was performed. An all-fields search for index terms ("depression" OR "depressive" OR "depressed") AND ("QT dispersion" OR "autonomic nervous system") was done. We included all articles that evaluated the relationship between QT dispersion on electrocardiogram and depression in patients without cardiovascular disease. Articles of revision, meta-analysis, editorials, and case reports were excluded. Outcome measures were either crude QTD or heart rate-corrected QT (QTcD) dispersions. The effect model was analyzed by MedCalc statistical software. The percentage of variability in the set of effect sizes due to true heterogeneity was tested with the I2 statistic. Results: The reviewers identified 677 publications. Four articles were included in the final analysis, which encompassed 267 cardiac health subjects (131 depressed and 136 non-depressed). There were 198 (74.1%) women. Age means did not differ between depressed and control groups. All studies reported significantly higher values of QTD and QTcD in depressed patients. As I2 values for crude QTD and QTcD were 79.49% to 83.48%, the random-effects model was used in this meta-analysis. The standardized mean difference was 1.493 (95% Confidence interval: 0.786-2.201; standard error: 0.36; Z-value = 4.135, p < 0.001) for crude QTD . For QTcD, the standardized mean difference was 1.441 (95% confidence interval: 0.739-2.143; standard error: 0.356; Z-value = 4.042, p < 0.001). respectively. Conclusion: Depression is associated with increased QT dispersion in healthy cardiac subjects. Our data suggest that depression could be associated with changes in cardiac electrophysiological properties, which may predispose these individuals to cardiac arrhythmias. 109666 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Proposal of a New Algorithm for Tachyarrhythmias's Management During Pregnancy Including Drug Safety BRUNA SANTI DOS SANTOS1, Eduardo Bartholomay1, Adriano Kochi1, Karina Andrade1, Bruna May1, Thais Nicola1, Cristiano Jaeger1, Daniel Souto Silveira1, Eduardo Schlabendorff1, Cicero de Campos Baldin1, Euler Manenti1 (1) Hospital Mae de Deus Background: Due to advanced maternal age, cardiovascular risk factors, and the successful management of congenital heart disease conditions, the prevalence of cardiovascular disease complicating pregnancy is rising. When arrhythmias are present, they may increase fetal and pregnant morbidity and mortality. The use of medications during pregnancy requires a thoughtful approach, balancing fetal and maternal risk. Therefore the management of tachyarrhythmias during pregnancy including drug safety should be a core knowledge area for all physicians who work with emergency, obstetrics or cardiology. Objective: Our purpose is to facilitate the approach of tachycardias in pregnant women by presenting a new algorithm based on the current evidence regarding the management of this pathology including drug safety in this group. Methods: Formulation of a new algorithm for tachyarrhythmias's management during pregnancy including drug safety. Results: The new algorithm proposed is presented in the figure. Conclusion: Besides rising prevalence of cardiovascular disease complicating pregnancy, any arrhythmia's treatment must be carefully evaluated, aiming at the safety of the fetus and the mother, preventing both from taking unnecessary risks. We expect that the new algorithm presented considering drug safety in pregnant women facilitates the approach of tachyarrhythmias in these patients. 109674 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Application for Decision-Making About Nursing Diagnoses of Patients with Heart Failure: Methodological Study ALYNE SANTOS BORGES1, Alyne Santos Borges1, Ana Carla Dantas Cavalcanti1, Flavio Luiz Seixas1, Paola Pugian Jardim1 (1) Universidade Federal Fluminense This study developed and evaluated an application for clinical decision-making in the care of patients with heart failure, registered at the National Institute of Industrial Property. As a general objective to develop and evaluate a mobile application based on the classification of nursing diagnoses from NANDA International Inc. for clinical decision-making in the care of patients with heart failure. As specific objectives: to map the defining characteristics of priority nursing diagnoses; develop an application for mobile devices for clinical decision making, and; to evaluate the usability of the application for clinical decision-making in the care of patients with heart failure. Method: This is a methodological study, carried out in three phases. In the first phase, the conceptual definition was carried out from the survey of the nursing diagnoses of the previously validated Nursing Consultation Instrument of the Heart Failure Clinic Coracao Valente. A scope review was carried out with the objective of mapping the nursing diagnoses of patients with heart failure. In the second phase, the Nursing DiagnosIC mobile application was developed through meetings of a scientific committee composed of researchers from Nursing and Computer Systems. In the third phase, an evaluation of the usability of the application was carried out by expert nurses and Information Systems undergraduates, using a predictive and prospective technique. Results: From the scope review, 41 articles, 14 nursing diagnoses and 147 defining characteristics of patients with heart failure were mapped. The application has 19 screens, 205 defining characteristics, 27 nursing diagnoses, subdivided into 11 domains, using the version (2018-2020). The evaluation of the application was carried out by two groups containing a total number of 16 participants. The Nursing DiagnosIC was considered to have good/excellent usability (75.3%). The evaluated heuristics received 55 points considered high usability. Conclusion: With the developed and validated application, it is expected to impact the care of patients with heart failure through a technology for clinical decision-making, with easy access to the accurate judgment of nursing diagnoses of patients with heart failure. 111070 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY The Association between Arterial Hypertension and Cancer Worsens Physical Capacity, Tumor Progression, Cachexia, and Heart Damage LUIS FELIPE RODRIGUES1, Bruno Rocha de Avila Pelozin1, Edilamar Menezes Oliveira1, Tiago Fernandes1 (1) School of Physical Education and Sport (EEFE), University of Sao Paulo (USP). Introduction: Cardiovascular diseases followed by cancers are the leading causes of death in the world. The bidirectional relationship between the diseases may potentiate cardiac damage and tumor progression, however little is known about their association. Our work aimed to investigate the impact of the association between arterial hypertension (AH) and cancer (CA) on physical capacity, tumor progression, cachexia percentage, and cardiac morphology in rats. Method: Wistar Kyoto (n = 18) and SHR (n = 18) male rats at 12 weeks old were assigned into 4 groups: Wistar Kyoto control (WKY), control tumor (WKY-T), SHR control (SHR), and SHR tumor (SHR-T). Walker-256 tumor cells (2.5 x 106 cells in 0.5 mL of phosphate-buffered saline) were subcutaneously injected into CA groups while control rats were injected with a vehicle. We assessed: tumor weight and growth, cachexia percentage (CP), grip strength, exercise tolerance, cardiomyocytes cross-sectional area (CSA), and left ventricular (LV) mass by LV: tibia length ratio. Results: SHR-T animals showed greater tumor growth (160%; p < 0.0001) and weight (96%; p < 0.05) compared to WKY-T group. In addition, SHR-T showed a higher CP (10 +- 1.96%; p < 0.001) compared to WKY-T group (2.84 +- 0.42%). The SHR showed a higher maximal muscle strength of hind limbs (2345 +- 81 g; p < 0.05) compared to WKY group (2033 +- 70 g). Otherwise, the association between AH and CA reduced the muscle strength in the SHR-T (1662 +- 94 g; p < 0.05) compared to the WKY-T group (1990.00 +- 35.29 g). Regarding the physical capacity, both groups with CA WKY-T (457 +- 44 m; p < 0.001) and SHR-T (297 +- 50 m; p < 0.001) developed exercise intolerance compared to WKY (695 +- 40 m); whereas the association between the diseases had even greater impairment in performance compared to CA alone. As expected, AH promoted cardiac remodeling by an increase in LV weight (23.9 +- 0.44 g/mm; p < 0.05) compared to WKY (21.96 +- 0.51 g/mm). However, both CA groups WKY-T (20.17 +- 0.44 g/mm; p < 0.0001) and SHR-T (20.54 +- 0.5 g/mm; p < 0.0001) showed a reduction in LV weight compared to WKY. This reduction in LV weight was accompanied by a reduction in cardiomyocytes CSA in the SHR-T (399 +- 11 mm2; p < 0.05) compared to SHR group (458 +- 12 mm2), highlighting that the combination of both diseases contributes to cardiomyocyte atrophy. Conclusion: Our data highlight the harmful effects of the bidirectional relationship between AH and CA on physical capacity, tumor progression, cachexia, and cardiac damage. 109709 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Adaptation and Validation of the Edmonton Symptom Assessment System for Patients with Heart Failure in Palliative Care PAOLA PUGIAN JARDIM1, Ana Carla Dantas Cavalcanti1, Bruno Bompet dos Santos1, Alyne Santos Borges1, Camila Achao Rosa1, Paula Vanessa Peclat Flores1 (1) Universidade Federal Fluminense (UFF) Introduction: Heart failure (HF) is considered a complex syndrome, characterized by a wide range of symptoms. Because it is a progressive chronic disease that limits life, there is a growing recognition of the important role of palliative care in HF. Symptom control is one of the goals of palliative care, but its assessment in HF remains a challenge. The Edmonton Symptom Assessment System (ESAS) scale has been used for this purpose in cancer patients, however, to our knowledge, there are no validated scales for use in monitoring the severity of HF symptoms. Objective: To adapt and validate the content of the ESAS for use in patients with HF in palliative care. Method: Methodological study divided into three phases: of content through a scoping review of the main signs and symptoms of HF in palliative care; of the ESAS content, based on the symptoms found in the scoping review and on the symptoms of the original version of the ESAS; and of the content through a committee of 30 expert judges. For analysis, the content validity index >=0.80 was adopted. Results: The first version of the ESAS for use in IC (ESAS-IC) consisted of 33 symptoms. The ESAS-IC was evaluated by 16 nurses, 6 cardiologists, 4 physiotherapists, 2 psychologists, 1 nutritionist and 1 educator, 2 of them were palliative care professionals. Most specialists were female (83.3%), with a median age of 35 years old and an interquartile range of (32-41.5) years. The group consisted of 14 masters, 8 specialists, 7 doctors and 1 bachelor, with a median of experience working with HF of 7.5 years and an interquartile range of (3.75-10.25) years. After analysis, 23 symptoms were validated and after suggestions from experts, the second version of the ESAS-IC was composed of 20 symptoms (pain, shortness of breath, tiredness/weakness, sadness, sleep, anxiety, swelling/edema, cough, loss of weight, feeling of well-being, dizziness, urinary incontinence, numbness/tingling, weight gain, problems with sexual interest/activity, self-esteem concerns, mental confusion, Improved ability to perform activities of daily living, spiritual well-being and memory). Conclusion: This study adapted and validated the ESAS content for use in patients with HF. However, there is still a need for further validation. The use of the ESAS-IC can contribute to improving the health outcomes of patients with HF, in terms of quality of life, symptom control and readmissions, among others. 109726 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Assessment of Religiosity and Spirituality in the Care of Patients with Systemic Arterial Hypertension: Is There an Influence? STEPHANIE RODRIGUES SCHAFF1, Elise Souza dos Santos Reis1, Mario Augusto Cray da Costa1, Cassiano Ianke1 (1) Universidade Estadual de Ponta Grossa - Parana Systemic arterial hypertension (SAH) is a public health problem and an important risk factor for cardiovascular diseases. Religiosity/spirituality (R/S) are practices that can interfere both in adherence and in the therapeutic goals of certain diseases. Objective: To evaluate the degree of influence of R/S in the drug treatment of SAH. Method: Study carried out at the cardiology outpatient clinic of a high complexity hospital (HAC) and a basic health unit (UBS) from September to December 2020 and August to December 2021, respectively. A total of 240 patients were evaluated using accredited scales to assess R/S and treatment adherence. Patients were divided into two groups: group with R/E and group without R/E. The p value was considered significant with p < 0.05. Results: In the general group there was a predominance of females (68.4%) in the group with R/S and males (54.1%) in the group without R/S (p: 0.006). White skin color prevailed in both groups with statistical difference (79.3% x 67%, p: 0.069). The other sociodemographic characteristics had no statistical difference between the groups. Regarding therapeutic adherence, the prevalence of high adherence was obtained both in the group with and in the group without R/S (82% x 69%, p: 0.026). The group with R/S from HAC achieved greater achievement of therapeutic goals (52.8% vs. 35.5%, p: 0.033). At the UBS, there was a high degree of adherence in both groups, with a statistical difference (83.3% x 63%, p: 0.011). Conclusion: Hypertensive patients with R/S had a greater adherence to treatment. 109730 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Treatment with Aliskiren Reverses Ultrastructural Changes Caused by Hypertension in Model 2K1C LUCIANA LONTRO ALVES1, Carolina da Silva Valentim1, Priscila Gomes Pereira1, Raissa Leal de Carvalho dos Santos Cunha1, Kissila Rabelo1, Bianca Torres Ciambarella1, Ana Lucia Rosa Nascimento1, Jorge Jose de Carvalho1, Jemima Fuentes Ribeiro da Silva1 (1) Universidade do Estado do Rio de Janeiro (UERJ) Renovascular hypertension (RH) is characterized by an increase in systemic blood pressure due to partial or total obstruction of the renal artery leading to overstimulation of the renin-angiotensin-aldosterone system. RH is potentially reversible and the system blockers are the ones chosen to control blood pressure. We aimed evaluate the antioxidant enzymes profile and tissue remodeling in the carotid artery of Wistar rats induced to HR by the two kidneys one clip (2K1C) model proposed by Goldblatt. Animals were divided in groups: SHAM; 2K1C; 2K1C+A. Treatment was administered via orogastric gavage with Aliskiren (10 mg/kg/day) for 30 days. Was performed electron microscopy and immunohistochemistry for collagens, metalloproteinases (MMPs), superoxide dismutase 1 (SOD1), catalase and glutathione reductase (GSH). Collagen I had greater staining in the hypertensive groups and aliskiren decreased your distribution. Collagen III was more expressed in the SHAM and the 2K1C+A present reduced expression. MMP2 show in the 2K1C an irregularity in the distribution and a more intense expression and the treatment decreased the marking. MMP9 2K1C showed more intense marking in concentrated areas, the treatment had no changes. Both catalase and GSH showed greater immunostaining in the SHAM group compared to the hypertensive groups. SOD expression was predominant in groups with hypertension. Oxidative stress enzymes showed no differences with treatment. Electron microscopy 2K1C generated alterations in endothelial cells, observed: pyknotic nucleus, poverty of organelles and decrease in their adhesion. We visualized fragmented and disorganized elastic lamellae. The treatment, these characteristics were not observed, indicating that Aliskiren contributed to the preservation of the carotid ultrastructural tissue. The SHAM group, on the other hand, presented ultrastructural characteristics expected for a control group. In conclusion, hypertension generated structural and ultrastructural changes in the carotid artery, that were reversed or preserved with the administration of Aliskiren. Oxidative stress had no effect with treatment. 109737 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Usability of Cardiac Defibrillators by Healthcare Professionals PAULA RODRIGUES DOS SANTOS PIRES1, Monaliza Gomes Pereira1, Renato Dias Barreiro Filho1, Renata Flavia Abreu da Silva2 (1) National Institute of Cardiology - INC; (2) Federal University of the State of Rio de Janeiro - UNIRIO Introduction: Technological advances and the increase in healthcare complexity have made it important to emphasize the concept of usability, which can be understood as the ability of a product to be used in the face of a specificity to users, objectives and context. The usability of high-risk medical devices, such as defibrillators, is highlighted due to their clinical importance in their proper management and their potential to cause harm to patients and professionals who operate them. Objective: To identify the usability of defibrillators focusing on the recognition of their model type, wave type and the ideal selection of the load to be used. Method: Descriptive study with a quantitative approach carried out with healthcare professionals in a public system hospital, located in the city of Rio de Janeiro (RJ), Brazil (BR), whose data collection took place between March and May 2021. The population of the study were healthcare professionals, namely, nurses, physicians, nursing residents and medical residents, allocated in care for adult patients and operating the cardiac defibrillator in clinical practice. There were no exclusion criteria. Sampling was done for convenience, with the sending of a semi-structured online questionnaire, which was divided between questions about the professional profile and about the operational usability and technical domain of the defibrillator in use in the subject's sector. The study was approved by the Research Ethics Committee and received number 4,489,535 and 4,499,886. Results: 58 healthcare professionals took part, being 40 (69%) nurses, 14 (24%) doctors and 4 (7%) not identifying their professional category. When questioned, 34 (59%) healthcare professionals answered correctly about the defibrillator in their unit. The majority, 45 (78%), could not report the defibrillator wave in their sector. As for the energy load, 25 (43%) participants were unable to relate the manufacturer's recommendation for the defibrillator in their unit and 28 (48%) subjects were not able to inform the American Heart Association's recommendation, both in situations of shockable rhythms. Conclusion: Gaps were identified in the knowledge of healthcare professionals attending in the study regarding the use of the defibrillator, necessary for its handling, which may negatively influence its usability. 109904 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Case Series of Patients Undergoing HV Measurement Simultaneously with Transcatheter Aortic Valve Replacement PATRICIA FERREIRA DEMUNER1, Daniel de Magalhaes Freitas1, Giulliano Gardenghi1, Silvio Roberto Borges Alessi1, Mauricio Lopes Prudente1, Fernando Henrique Fernandes1, Ellen Goncalves Guimaraes1, Debora Rodrigues1, Max Weyler Nery1, Ricardo Curado de Oliveira e Silva1, Larissa Xavier Alves de Oliveira1, Fernando Araujo Cintra Canedo1 (1) Hospital Encore Introduction: Transcatheter aortic valve implantation (TAVI) is one of the treatments of choice for patients with severe aortic stenosis. In the last decade, there have been technical and technological advances, but there has been no decrease in the number of cases requiring permanent pacemaker implantation (MPD): those with total atrioventricular block (TAVB) or second-degree Mobitz type II. One of the predictors of the need for MPD is the development of a left bundle branch conduction disorder, which can be diagnosed even in the subclinical form in an invasive way by measuring the his-ventricular interval (HV). Data on the impact of left bundle branch block after TAVI are scarce and treatment is individually tailored leading to marked differences in clinical management. Objective: To describe a series of 7 cases of patients undergoing TAVI simultaneously with the electrophysiological study (EPS), in order to immediately assess the need for MPD after implantation. Material and Methods: 7 patients were evaluated (4 males; mean age 80 years; mean BMI 23.3) whose data were collected in the Tasy(r) electronic medical record system and tabulated and analyzed by excel(r). The EPS was performed with a quadripolar diagnostic catheter and positioned in the bundle of His to measure the HV interval, when the HV measurement exceeded 70 ms, MPD implantation was indicated. For TAVI, the technique used was the same in all cases, with transfemoral access, under sedation and local analgesia, Sapien(r), Corevalve revolute R(r) and Evolut(r) prostheses, sizes ranging from 20 to 34 mm. Results: Among the patients analyzed, 4 evolved with left bundle branch block after TAVI. MPD implantation was indicated for 1 patient, the other patients underwent removal of the provisional MP while still in the hemodynamics room. The patient with an indication for MPD underwent implantation of the device during the same hospitalization, without intercurrences. The HV interval ranged from 46 to 58 ms (average 53,28) before the intervention, to 52 to 84 ms (average 62,8) after, approximately 18% positive variation. Only one patient died of an etiology unrelated to the procedure. No FES-related complications have been described. Conclusion: The FES strategy during TAVI seems to be a viable strategy to stratify patients for the risk of TAVB and 2nd degree Mobitz type II AVB in an early way, already referring them to appropriate treatment without demonstrating an increase in the risks related to the procedure. 109753 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Residential Blood Pressure Monitoring: Analysis of a Database of 1474 Patients MATHEUS TOSCANO PAFFER1, Matheus Vieira Cabral Figueiredo1, Carmen Beatriz Oliveira Silva Veras1, Francyelle Maria Barbosa Fonseca1, Pedro Toscano Paffer1, Ramon Barbosa Barros1, Tatiana Maria Toscano Paffer1 (1) Faculdade de Medicina de Olinda Introduction: Hypertension is a highly prevalent disease, being one of the main risk factors for cardiovascular events. With just the measurement of blood pressure in the medical office, white coat hypertension can occur, clinical condition characterized by abnormal blood pressure values in the office, but with values considered normal by home blood pressure monitoring (HRPA). The aim of this study is to analyze a HRBP database from a private cardiology clinic, showing cases of white coat hypertension. Methods: Evaluate the results of HMBP exam of 1474 patients from a private cardiology clinic in Recife/PE, Brazil. The device used in all patients was the Omron 705 CP Blood Pressure Monitor. Results: A total of 1474 patients, of which 57.8% were women, with a mean age of 53.4 years (+-16.17). The mean office measurement of systolic blood pressure was 130.68 mmHg (+-18.54) and diastolic 81.83 mmHg (+-11.55), the overall mean systolic pressure of the HRBP exam was 123.99 mmHg (+-14.3) and diastolic was 76.5 mmHg (+-8.99). Among this total, 196 patients (13.3%) who were diagnosed with white coat hypertension were analyzed separately. Of these 196, 50.5% were men and the mean age was 56 years (+-15.15). Mean office systolic blood pressure averaged 148.5 mmHg (+-11.79) and mean diastolic blood pressure of 90 mmHg (+-8.78). The overall mean of systolic blood pressure was 125 mmHg (+-6.78) and diastolic pressure was 76.4 mmHg (+-6.44). Conclusion: White coat hypertension has a significant prevalence in the total number of patients evaluated, evidencing the importance of using HMBP for the diagnosis of arterial hypertension. Therefore, it is important to follow the guidance of the main hypertension guidelines around the world, such as the European one, which guide the use of this test in the diagnosis of arterial hypertension. 109764 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION Anticoagulation and Clinical Outcomes in Atrial Fibrillation: Retrospective Analysis of a Regional Hospital ESTHER BOTELHO SOARES DA SILVA1, Conrado Roberto Hoffmann Filho1, Michele Tavares Mendonca1, Juliana Alzira Gonzales Oliveira1, Beatriz Vieira Roca1, Rafaela Louise Sales1, Joao Paulo Souza Brighenti1, Joao Paulo Panato Ribeiro1, Gabriel Erzinger1, Gilmar Sidnei Erzinger1, Jaqueline Barp1 (1) Hospital Regional Hans Dieter Schimidt Atrial fibrillation (AF) is the most frequent cardiac arrhythmia affecting 37.5 million worldwide. It's a major risk factor for ischemic stroke and has strong associations with other comorbidities. Age is one of the greatest risk factors to develop AF. Life expectancy is increasing as does AF incidence and prevalence, affecting approximately 10% of subjects over 80 years. Effective anticoagulation reduces the burden of disabilities and death caused by stroke. Assess real-world data from our institution and provide tools to improve our effectiveness in diagnosing and treating this disabling disease. Retrospective study based on medical records. The inclusion criteria were AF and atrial flutter. From May 2021 to January 2022, we analyzed one thousand medical records of patients treated at our institution. Most of the population was male (58.4%), white patients (96.4%). The presence of comorbidities was frequent, especially arterial hypertension and heart failure (80.8% and 52.3%, respectively). Breathing disorders were present in 36.3% while diabetes corresponded to 32.8%. Coronary artery disease 28,1%, kidney disease 12,8%, cerebrovascular disease 8.7% and tobacco use 8.6%. 33.3% of patients had paroxysmal AF, 50.6% permanent, 8% persistent, 5.3% flutter and 2.8% indeterminate. The mean age for men was 66.9 years and for women 69.9 years. Male mean CHADSVASC was 3.2 HASBLED 1. Average female CHADSVASC was 4.4 HASBLED 2. The BMI for men was 28.4 kg/m2 and 29.3 kg/m2 for women, mean CKD EPI was 65. Comparing the number of strokes a greater rate was observed with warfarin versus DOAC (20.27% and 17.83% respectively). Regarding bleeding, the rate was 5.3% with DOACS and 6.37% with warfarin. The total death rate with DOACS was 10.36% and with warfarin 15.83% with an absolute risk reduction of 5.47% (p = 0,003). In the stroke analysis, patients treated with warfarin had a higher rate when compared with DOAC (p = 0,021). In this study of a public health care service, it was observed that a large percentage of patients were using DOAC therapies. It was also observed that the rate of bleeding and stroke was lower with the use of DOACs, however without statistical significance by chi squared test. The overall death rate was shown to be reduced in favor of DOAC therapy over warfarin. In the final analysis, comparing stroke patients, those treated with warfarin had a higher rate when compared with DOAC. One explanation could be the lack of adequate adjustment of the INR. 109789 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Nanomedicine Associated with Coronary Artery Disease: A Theragnostic Method? GUSTAVO SANTOS PORFIRO1, Gustavo Santos Porfiro1, Leonardo Favaro Pereira1, Lucas Dalvi Armond Rezende1, Helena Alves de Andrade Ribeiro1, Fernando Luiz Torres Gomes1 (1) Universidade Federal do Espirito Santo Introduction: Cardiovascular diseases are the most common cause of death around the globe, with approximately 17.9 million people dying from heart attacks in 2021, representing 31% of global deaths. The rupture of atheromatous plaques is a major health problem and the main cause of heart attacks. Despite new technological advances for the diagnosis and treatment of coronary artery disease, early detection remains static, so that, commonly, myocardial infarction is the first clinical manifestation of this involvement. Thus, nanotechnology has been opening new horizons in the theragnostic perspective for the improvement and prevention of cardiac conditions such as coronary artery disease. Objective: To perform an integrative literature review to establish the main findings and relationships between coronary artery disease and nanoparticles. Methods: The method of integrative literature review was adopted, covering the period from January 2022, in the PubMed and Cochrane Library databases, using the descriptors: nanoparticles, coronary artery disease, and nanomedicine. Results: Sustained evidence was found about the miRNA of atherosclerotic plaque and the synthesis of nanoparticles, being characterized with low toxicity and anti-inflammatory properties, attenuating atherosclerosis, which would ease the cases of myocardial infarction due to atherosclerotic obstruction. Conclusion: The use of antibodies and peptides that recognize markers associated with cardiovascular disease has allowed the development of a more current generation of selective nano-systems. However, further studies on how nanoparticles can act in the intra-atheroma environment are needed to improve the understanding of nanomedications, generating important therapeutic contributions. 109790 Modality: E-Poster Young Researcher - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Comparison of Religiosity/Spirituality of Hypertensive Patients between Primary Health Care and High Complexity Hospital STEPHANIE RODRIGUES SCHAFF1, Elise Souza dos Santos Reis1, Mario Augusto Cray da Costa1, Cassiano Ianke1 (1) Universidade Estadual de Ponta Grossa - Parana Introduction: Systemic arterial hypertension (SAH) is a public health problem and an important risk factor for cardiovascular diseases. Religiosity/spirituality (R/S) are practices that can interfere both in adherence and in the therapeutic goals of certain diseases. Objective: To compare the degree of influence of R/S in the drug treatment of SAH in hypertensive patients who adhere to religious practices in a high-complexity hospital (HAC) and a basic health unit (UBS). Method: Study carried out at the cardiology outpatient clinic of a HAC and UBS from September to December 2020 and August to December 2021, respectively. A total of 155 patients were evaluated according to accredited scales to assess R/S and treatment adherence. Patients were divided into two groups: group with R/S from HAC and group with R/S from UBS. The p value was considered significant with p < 0.05. Results: There was a predominance of females in both the HAC and UBS R/S groups (60.7% x 78.8%, p: 0.016). Regarding marital status, there was a predominance of married people in both groups (53.9% x 68.2%, p: 0.003). The other sociodemographic characteristics had no statistical difference between the groups. Regarding therapeutic adherence, the prevalence of high adherence was obtained both in the group with R/S from the HAC and from the UBS (80.9% x 83.3%) with no statistical difference. With regard to therapeutic goals, both groups achieved goals in more than half of the interviewees (52.8% x 56%). Conclusion: Hypertensive patients with R/S from both HAC and UBS had greater adherence to treatment and achievement of therapeutic goals by more than 50%. 109796 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION A Walking Diary in Phase-1 Cardiac Rehabilitation: A Randomized Clinical Trial GABRIELA LAGO ROSIER5, Gleide Glicia Gama Lordello1, Patricia Alcantara Doval de Carvalho Viana2, Luiz Eduardo Fonteles Ritt3, Gilson Soares Feitosa Filho4 (1) Bahiana School of Medicine and Public Health; (2) Hospital Santa Izabel, Santa Casa da Bahia; (3) Hospital Cardio Pulmonar; (4) Hospital Alianca; (5) UniFTC Introduction: Inpatient rehabilitation is extremely important for patients recovering from cardiac surgery. Although a walking diary is routinely used in clinical practice, it has yet to be adequately tested and reported in the literature. Objectives: To establish whether use of a walking diary affects the number of steps taken following cardiac surgery and whether this is related to the patient's level of cardiac anxiety. Methods: An open, controlled, randomized clinical trial was conducted at a referral hospital in cardiology with adult patients submitted to elective valve and/or coronary surgery, who had no motor impairment. Following discharge from the intensive care unit, all the participants used a pedometer to register the number of steps taken over five consecutive days. Twenty-nine individuals were randomized to an intervention group to use the walking diary as treatment strategy, while twenty-three were allocated to a control group. Statistical significance was defined as p < 0.05. A statistician blinded to patient allocation conducted the analysis on an intention-to-treat basis. Results: The groups were similar regarding their demographic, clinical and surgical characteristics. Mean age was 59.3 +- 13 years, most participants (76.9%) were male, and the most common type of surgery was myocardial revascularization (57%). There was no difference between the groups regarding the total number of steps taken: control group = 1,496 (477.5-2992.5) vs. intervention group = 1,468.5 (494.2-2,678) (p = 0.902). Conclusion: Use of the walking diary had no effect on the number of steps taken and was unassociated with the level of cardiac anxiety in inpatients following cardiac surgery. 109797 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION New Method to Fix Temporary Pacemakers in Order to Reduce Cable Displacements and Loss of Pacing HEIGLON ESTEVAO BONELLA DENTI1, Vitor Boniatti Neves2, Edimar Lima3 (1) Universidade Federal da Fronteira Sul - Campus Passo Fundo; (2) Faculdade IMED; (3) Hospital de Clinicas de Passo Fundo Transvenous temporary pacemaker (PM) is very useful for patients with severe bradycardia. Studies that analyzed its complications estimated that the rate of loss of capture is up to 43%. They have also found that the displacement of the PM cable requiring repositioning is one of the most common complications, occurring in 32% to 38% of the procedures performed. Cable displacement occurs because kits manufactured to install the devices do not have effective methods to lock in the pacemaker cable. This study proposes a simple, inexpensive and effective change in the temporary transvenous pacemaker kit (please see image attached). The original kit has a thread (blue color in the image attached) that locks the cable at the distal end of the contamination protection cap, but between this thread and the introducer the cable is relatively loose (it does not have a good fixation). Currently, the thread (in blue as seen in the image attached) is kept at the distal end of the protective cap as it is produced. The change this study proposes is to remove the blue thread from the distal end and to adapt this thread inside the plastic to the proximal end of the protective cap, securing it to the end of the introducer. Thus, it is possible to handle and to reposition the cable, if necessary, without losing the sterile environment. On the other end, instead of the thread, one could fix the plastic with micropore so there is no displacement of the protective cover over the cable which could accidentally reduce the sterile area. In this way, the cable is locked at the end of the introducer and does not allow displacements. With the proposed change, the sterile area of the cable is kept inside the protective cover, and it is still possible to loosen the cable if necessary and retighten after handling it because the blue thread will remain inside the protective cover (wrapped by sterile plastic). We concluded that this is an effective way to assemble the transvenous PM kit (from the attached photo) to avoid the loss of pacing due to cable displacement. This modification can be carried out when manufacturing the kit. 109798 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Systematic Review of Transcatheter Versus Surgical Aortic Valve Replacement in High-Risk Patients with Severe Aortic Stenosis: The Choice of Treatment Influences Mortality Rates Over the Years? LEONARDO TORREAO BEZERRA CAVALCANTI1, Glaudir Donato Pinto Junior1, Ana Karolina Bento da Silva1, Livia Farias de Holanda Furtado1, Manasses Almeida do Nascimento1, Gustavo Gomes Santiago1, Lucas Caetano da Silva1, Andressa Alves de Carvalho1, Wanessa Alves de Carvalho1, David Cesarino de Sousa1, Marcela Lukerli Araujo Paulina da Silva1, Evellyn Pereira de Melo1 (1) Federal University of Paraiba, UFPB Introduction: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with aortic stenosis, especially at high surgical risk (HSR). However, the procedure is not always available at lower complexity health centers. Further, controversies remain regarding the impact of TAVR on long-term mortality compared to surgical aortic valve replacement (SAVR). Aims: To compare TAVR versus SAVR mortality over the years after the procedure from randomized clinical trials (RCT) with patients at HSR. Methods: We searched Medline, Embase, LILACS and SciELO on March 27th, 2022, for TAVR versus SAVR RCTs. Were included studies that provided mortality data in follow-up for both interventions performed in HSR patients. Were excluded duplicates and studies that did not meet the inclusion criteria. An independent review was performed by two authors following the PRISMA protocol. Results: After applying the eligibility criteria, 20 studies remained to be reviewed. These studies included follow-ups from days up to 5 years. Considering mortality within 30 days, there was no significant difference between patients undergoing TAVR or SAVR. However, some studies marked a greater association of perioperative complications, such as bleeding and atrial fibrillation, linked to SAVR invasiveness. Still, major vascular events and even intraoperative deaths were seen in TAVR intervention. Regarding mortality from 1 to 3 years after the procedure, the studies diverged: while some showed no difference, others reported a reduction in mortality in the TAVR group. This result was also found in studies evaluating patients with diabetes and patients with chronic lung disease. Moreover, prosthesis-patient mismatch (PPM) was significantly lower in TAVR compared to SAVR, which in severe PPM was related to increased risk of death at 2 years. Nevertheless, paravalvular regurgitation was found to be more frequent in TAVR, which was associated with lower survival rates. Overall, at follow-ups of more than 3 years, there was no significant mortality difference between the groups. Conclusions: For 1 to 3 years follow-ups, it was outlined an advantage for TAVR, especially in the groups with diabetes and chronic lung disease. However, the complications arising from both interventions do not seem to be associated with statistically different mortality rates, especially at longer periods of follow up. 109984 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Associated with Anabolic Steroid Use: A Systematic Review EDUARDO FRANCO CORREIA CRUZ FILHO1, Eduardo Franco Correia Cruz Filho1, Ana Carolina Souza Diniz1, Fernando de Paiva Melo Neto1, Emanuel Francisco de Carvalho Pinto3, Lucas Vinicius Rafael Figueiredo1, Lorena Souza dos Santos Lima1, Lais Nobrega Diniz3, Gustavo Nobrega de Melo2, Gustavo Soares Fernandes1 (1) Centro Universitario de Joao Pessoa - UNIPE; (2) Faculdade de Ciencias Medicas da Paraiba - FCM; (3) Faculdade de Medicina Nova Esperanca - FAMENE Introduction: Anabolic androgenic steroids (AAS) are widely used for cases of osteoporosis, hypogonadism, Turner syndrome, hormone therapy in climacteric women, and are even used without indication as a form of treatment to increase physical performance. However, its use has several important adverse reactions in the cardiovascular system, often fatal to the individual, which make its use controversial and in most cases contraindicated. Objective: The present study aims to evaluate the cardiovascular risk of AAS use. Methods: A systematic literature review study, based on the PRISMA methodology, conducted with published articles on the Virtual Health Library and the United States National Library of Medicine (PubMed), between 2017 and 2022. The descriptors utilized were "Cardiovascular Disease" and "Anabolic Agents", and their variations, associated with the Boolean operators "AND" and "OR". Results: Initially, 57 articles were selected, which were chosen for manual selection based on their abstracts. In this way, duplicated articles and whose themes did not fit the objectives of the work were excluded, thus, 07 articles were chosen for the present work. Of the 07 articles involved, 05 are literature reviews, 01 meta-analysis and 01 case report. Among the studies evaluated, 100% highlighted the negative cardiovascular effects of steroid use, of which 85% evaluated these risks in the general population, while 15% focused on the risks for postmenopausal women using hormone therapy. As for the substance's manifestations, the main alterations presented were: dyslipidemia (86%), coronary heart disease (86%), arterial hypertension (57%), cardiomyopathy (42%) and arrhythmia (42%). The meta-analysis that specifically evaluated the woman, compared tibolone with placebo and no treatment, especially evaluating its impact on lipoprotein (a) and the overall lipid profile. Conclusion: It is important to have well elucidated the cardiovascular risks due to the indiscriminate use and in supraphysiological doses of AAS, which in the long term can lead to negative and more severe outcomes. Furthermore, in order to evolve in this topic, more evidence-based therapeutic approaches are important, with clear objectives on the use of AAS and the risks of atherosclerosis, infarction and myocardial spasms and arrhythmias. 110051 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Cardiovascular Impact Glp-1 Receptor Agonist in Patients with Diabetes Mellitus Type II using Glp-1 Receptor Agonist EDUARDO FRANCO CORREIA CRUZ FILHO1, Eduardo Franco Correia Cruz Filho1, Camila Araujo Novais Lima1, Anna Julie Medeiros Cabral1, Gabriel Lucena de Carvalho Soares1, Waneska Lucena Nobrega de Carvalho2 (1) Centro Universitario de Joao Pessoa - UNIPE; (2) Universidade Federal da Paraiba Introduction: Diabetes Mellitus (DM) type II is a metabolic disease with a high incidence, affecting 370 million people worldwide. DM II generates systemic changes, allowing a series of secondary disorders, among them, the increase in cardiovascular risk. Adequate therapeutic management is relevant, mainly related to cardiovascular protection. In this context, the use of agonists of the peptide similar to Glucagon I (GLP-1) has been increasingly highlighted, both in diabetics and in patients with heart disease. Objectives: To analyze major cardiovascular events in patients with type II DM using GLP-1 agonists. Methodology: This is a systematic review. The searches were performed using the PubMed database with works published in the last five years. The Health Sciences Descriptors used in the searches were: "Glucagon-Like Peptide-1 Receptor", "Diabetes Mellitus, Type 2" and "Cardiovascular Diseases", linked to the Boolean operator "AND". To ensure a better structuring and organization of the results, the PRISMA recommendation was used. Initially, 116 articles were selected, which were manually selected based on their abstracts, excluding duplicate articles and whose themes did not fit the objectives of the work. This final selection resulted in 02 articles. Results: A meta-analysis using 360 articles and 56004 patients with type II DM evaluated the occurrence of non-fatal myocardial infarction, non-fatal stroke and death from cardiovascular or undetermined causes (Major Cardiovascular Adverse Effects - MACE). In that study, a significant 12% reduction in MACE was found for patients using GLP-1 receptor agonists. In addition, another cross-sectional study with 4076 patients with type II diabetes, which assigned patients to the use of efpeglanatide (2717) or placebo (1359), showed that major adverse cardiovascular events occurred in 189 patients (7.0%) using of efpeglanatide and in 125 patients (9.2%) on placebo. Conclusions: In summary, GLP-1 agonists are currently widely studied, with effects in more than one area of interest and no longer a glucocentric perspective. Therefore, the most recent studies have shown an important application of this drug in patients not only with diabetes, but also with heart disease. The main point of attention is the reduction of MACE, as it represents a reduction in cardiovascular risk in patients with type II DM. 109884 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Qt Interval and Associated Measures Predict Prognosis of Patients with Acute Stroke? CATARINE BENTA LOPES DOS SANTOS1, Catarine Benta Lopes dos Santos1, Marcelo Bender Angst1, Sergio Ferreira de Ferreira1, Sheila Ouriques Martins1, Mauricio Pimentel1 (1) Hospital de Clinicas de Porto Alegre Background: The stroke is a relevant cause of mortality and disability around the world. Electrocardiogram is part of the clinical examination of patients with stroke and its alterations are used for the etiological and prognostic evaluation of the patients. Changes in ventricular repolarization assessed by measuring the QT interval and its associated variables have been recently studied in stroke patients. Objectives: To evaluate the association of measures of the corrected QT interval (QTc), QTc dispersion, Tpeak-T-end dispersion (Tpe-d) and ratio Tpe/QT with mortality and neurologic disability (Rankin Scale) in ischemic stroke patients in the hospital discharge and within 3 months. Methods: Retrospective cohort study including patients admitted with acute ischemic stroke in a tertiary university hospital. The measurements of the QTc, QTc-d, Tpe-d and Tp-e/QT intervals were performed by experts physicians. The outcomes evaluated were: total mortality and the Rankin Scale at hospital discharge and within 3 months. The comparison between groups was performed using the Kruskal-Wallis test. Results: A total of 170 patients were included, predominantly female (53%), with a mean age of 64.4 +- 12.4 years. The length of hospital stay was 14 +- 21 days. Mortality during hospitalization was 11.17% and the total at 3 months was 14.1%. The results are shown in the table in milliseconds. Conclusion: This cohort showed that QTc was higher in stroke patients who died within 3 months and those with worse Rankin at hospital discharge. The ratio Tpe/QT was lower in those patients who died during hospitalization. The assessment of ventricular repolarization expressed by the QTc interval and associated measures can identify more severe patients who need implementation of optimized treatment. 109886 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Assessment of Miocardial Strain in Aortic Stenosis RAISSA GABRIELA VIEIRA DA CAMARA BARROS1, RAISSA GABRIELA VIEIRA DA CAMARA BARROS1, EVELINE BARROS CALADO1, ELLEN MAGALHAES LISBOA ALVES1, MONICA DE MORAES CHAVES BECKER1, LUCIA MARIA VIEIRA DE OLIVEIRA SALERNO1, ROBERTO DE OLIVEIRA BURIL1, JOSE RENATO E MELO FIGUEIROA1, Eduardo Cavalcanti Lapa Santos1, TACITO CUNHA LIMA2, ROBERTO VIEIRA DA CAMARA2 (1) UNIVERSIDADE FEDERAL DE ; (2) UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE Aortic stenosis (AS) is the most common primary valve disease in the US and Europe. The gold standard diagnosis of AS is to perform a echocardiogram (ECO) and the measurements to classified the severity are: maximum jet velocity (Vmax), maximum and mean transvalvular pressure gradient (GM) and aortic valve area by the continuity equation. The miocardial strain assessment through the global longitudinal strain (GLS) is one of the most promising techniques for the early detection of reduced left ventricular ejection fraction (LVEF) and has become useful in AS scenario by correlating with the severity of AS. The GLS is a technique to assess the myocardial deformation suffered by myocardial fibers through Speckle tracking (normal value is below -18%). Several studies have already shown that the reduction in GLS precedes the decrease in LVEF, with relative reductions of 15% in GLS predicting a subsequent decrease in LVEF. This study aims to detect early changes in ventricular systolic function not only based on LVEF by Simpson's method, but also through the assessment of the GLS in the AS and to correlate the pattern of changes in the GLS with the degree of stenotic impairment observed. General objective: Assess global and segmental LV systolic function through myocardial strain in aortic stenosis. Secondary objectives: Characterize the distribution pattern of the GLS in the AS; correlate the degree of AS with the myocardial GLS; correlate LVEF by Simpson's method and GLS. Methods: This is an observational, descriptive, cross-sectional study. Results: A total of tirty patients were obtained, with a prevalence of 33% of major AS, 36.7% of moderate AS, 16.7% of mild AS and 13.3% of paradoxical AS was evidenced. An inverse relation between the severity of the AS and the GLS could be seen, that is, the more severe the stenosis, the lower the GLS value. We observed an average GLS in important AS of -17.6%, in moderate AS of -18.86%, in mild AS of -19% and in paradoxical AS of 16.85%. Regarding the pattern of segmental distribution of GLS values, there was a greater involvement of the mid-basal segments than the apical segments of the LV. Conclusion: The present study suggest a progressive impairment of LV systolic function assessed by the GLS as the severity of AS progresses, even though there is no direct impact on the LVEF measurement what can be primordial on the decision of early valve replacement despites the severity of AS founded on ECO. 109890 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Alcohol Ablation Versus Surgical Myectomy in the Treatment of Obstructive Hypertrophic Cardiomyopathy: A Systematic Review using the Prisma Method ANA LIGIA VALERIANO DE OLIVEIRA1, Matheus Araujo Borges1, Gabrielly de Souza Correia1, Eduarda Tatico Lagares1, Lucas Eduardo Almeida Franca1, Isabela Castro Pereira1 (1) Pontificia Universidade Catolica de Goias Introduction: Alcoholic septal ablation (ASA) consists of a selective infusion of high-grade alcohol in a septal branch that supplies the basal interventricular septum. It is a technique used as an alternative to surgical myectomy in obstructive hypertrophic cardiomyopathy (HOCM). The procedure seeks to create an iatrogenic infarction and, as a consequence, reduce left ventricular outflow tract (LVOT) obstruction. AAS has been improved over time, with benefits similar to myectomy. Objective: To analyze the benefit of treating hypertrophic obstructive cardiomyopathy with alcohol septal ablation as an alternative to myectomy. Methodology: This is a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA methodology. The literature search was carried out between January and February 2022, using the Scientific Electronic Library Online (SciELO), PubMed and Latin American and Caribbean Literature (Lilacs) databases. Thirty-three articles were selected, in English and Portuguese, excluding those that did not fit the objectives of this review and the methodological recommendations. The filters used were "human" and "published in the last 10 years". The descriptors used were "obstructive hypertrophy cardiomyopathy", "myectomy" and "alcohol ablation". Results: Rigopoulos et al., found that threatening arrhythmic events seem be rare after ASS and occur more in patients with an estimated very high risk of sudden death. One study confirmed these findings, finding ventricular tachyarrhythmia or 30-day sustained ventricular fibrillation in only 7% of patients. ASS is a therapeutic alternative in patients with advanced age or comorbidities and showed shorter hospital stay and reduced post-procedure pain. Naidu et al., concluded that ASS results were similar to those of myectomy up to 8-10 years, in 90% of patients. showed to be able to reduce LVOT and relieve symptoms. Another relevant finding was the need for experienced services to perform SSA so that complications are less and the greatest therapeutic effects. Conclusion: AAS has become an alternative to myectomy that can be considered in carefully selected patients. Data show similar functional and hemodynamic benefit to myectomy, in addition to shorter hospital stay, reduced pain and associated complications. 109942 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Decreased T3 Levels as a Marker of Clinical Worsening in Patients with Sars-Cov-2 and its Correlation with Serum Troponin at Diagnosis - a Retrospective Cohort Study VITOR FEUSER DA ROSA1, Guilherme Pinheiro Machado1, Victor Henrique Ignacio de Souza1, Georgia Martina Chichelero1, Simone Magagnin Wajner1 (1) Hospital de Clinicas de Porto Alegre Introduction: The SARS-COV-2 pandemic had a great impact on the morbidity and mortality of affected patients. T3 has a direct impact on cardiomyocytes, causing myocardial injury in patients with SARS-COV-2. Clinical observations have revealed a relatively high (up to 64%) prevalence of sick euthyroid syndrome among COVID-19 patients, with some exhibiting a profound decrease in thyroid hormone levels. We know that low levels of T3 in sick patients occur early, correlate with disease severity, and that normalization of hormone serum concentrations is related to clinical recovery. Objective: The objective of the study is to describe the changes in thyroid hormones present in patients diagnosed with COVID-19. The primary outcome of the study is to assess the relationship between T3 levels and the degree of cardiac involvement. Methods: Samples from PCR positive patients for COVID-19 who were referred for admission to the ward or clinical ICU of a tertiary hospital were included. Serum samples stored in the COVID-19 biobank at Hospital de Clinicas de Porto Alegre were used. Half of the samples collected in the year 2020 and half collected in the year 2021 were requested. In the requested serum, T3 levels were measured on arrival at the hospital and around day 7 of hospitalization. Results: The number of patients enrolled in the study was 119. The mean age of patients was 61 +- 29 years. About 31.09% of the patients in the study died and 68.90% were discharged from the hospital. Among patients who died, T3 on the 1st day of hospitalization had a mean of 52.01 +- 16.48 and among patients who were discharged, the mean T3 on the first day of hospitalization was 62.25 +- 22, 14. On arrival at the hospital, among those who died, the mean troponin was 623 +- 152 and among those who were discharged was 176 +- 34.5. The T3 levels on the 7th day of the patients who died had an average of 42.66 +- 7.22 and of those who were discharged it was 60.98 +- 21.53. Conclusion: The study seeks to evaluate two tests that are relatively possible to obtain in patients admitted to hospitals of great complexity in the context of the COVID-19 pandemic, with the objective of helping medical teams in taking conducts and evaluating the prognosis of these patients. It is possible to infer that patients who have T3 levels below 50 have a higher risk of death associated with elevated troponin values, regardless of other clinical factors. 112331 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY A New Machine Learning-Based Model for Risk Stratification of Patients Undergoing Ventricular Tachycardia Ablation PETER VAMOSI1, Marton Tokodi1, Patrik Toth1, Ferenc Komlosi1, Istvan Osztheimer1, Peter Perge1, Katalin Piros1, Zoltan Sallo1, Nandor Szegedi1, Bela Merkely1, Laszlo Geller1, Klaudia Vivien Nagy1 (1) Semmelweis University Heart and Vascular Center, Department of Cardiology Background: Monomorphic ventricular tachycardia (VT) is a life-threatening condition. Catheter ablation is an effective treatment method for many patients, but significant variability is observed in postprocedural mortality, due to the high burden of comorbidities and other factors. Therefore, there is a high need for an accurate risk stratification system. Aim: We sought to implement a machine learning pipeline to predict 1-year all-cause mortality in patients undergoing VT ablation. Methods: For 265 consecutive VT ablation patients at our center, we processed procedural, demographic and medical history data, their laboratory and echocardiographic findings (63 parameters). To predict 1-year all-cause mortality, several supervised machine learning models were trained and evaluated using 5-fold cross-validation with applying recursive elimination to identify the optimal subset of input features. We quantified their performance with the area under the receiver operating characteristic curve (AUC); we identified the most important predictors by Shapley values. Finally, we used topological data analysis to visualize patient subgroups with different mortality risks. Results: 57 (22%) patients died during the 1-year follow-up. The best predictive performance was achieved by a random forest model with 18 input features [AUC: 0.73 (95% CI: 0.68-0.78)], which significantly outperformed previously published risk scores (I-VT [AUC: 0.63 (95% CI: 0.55-0.70), p < 0.001], PAINESD [AUC: 0.63 (95% CI: 0.55-0.71), p = 0.009]). The most important predictors were mitral E-wave deceleration time, cardiac resynchronization therapy, age, electrical storm, and hemoglobin concentration. In the topological network based on the input features of the above model, we identified five groups with differing clinical characteristics and mortality rates . Conclusions: Our machine learning model could effectively predict 1-year all-cause mortality in VT ablation undergoing. Thus, it facilitates the identification of high-risk patients and the personalization of treatment and follow-up strategies, ultimately leading to improved outcomes. 109975 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Literature Review: Left Ventricular Noncompaction of the Myocardium CAROLINE TEIXEIRA BERNARDI3, Beatriz Sadigursky Nunes Cunha1, Rafael Fortes Locateli1, Giana Bevilacqua Schmitz1, Barbara Muller Rettore1, Gustavo de Lemos Souza1, Sergio Rosas de Barros Neto1, Angela Quatrin Campagnolo1, Lucca Corcini Biscaino2, Pedro Miguel Mariussi3, Sergio Luis Pereira Furtado1 (1) Universidade Federal de Santa Maria - UFSM; (2) Universidade Franciscana - UFN; (3) Hospital de Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP Introduction: Left ventricular noncompaction (LVNC) is defined as a pattern of prominent trabeculae, intra-trabecular recesses, and a thin compacted layer on the left ventricular (LV) wall. It is an entity with yet unclear physiopathology, and may be congenital or acquired. The prevalence ranges from 0,014 to 1,3%. Objective: Summarizing LVNC's main findings of clinical manifestations, etiology, diagnosis, prognosis and treatment. Methodology: Our research was conducted on PubMed with using "Isolated noncompaction of the ventricular myocardium", and papers from the last 5 years were selected. 188 results were found and a selection was made from their abstracts and afterwards from reading the full article. The final number of selected articles for this review was 58. Results: LVNC's clinical presentation may range from an asymptomatic entity to more serious manifestations, such as arrhythmias, heart failure and embolic events. Genetics play an important role in this condition, although a definitive correlation between genotype and phenotype has not yet been established. LVNC is similar to other cardiomyopathies, genetically heterogeneous and more frequently inherited as a dominant autosomal disorder or related to the X chromosome. There are no gold standard criteria for its diagnosis, which leads to many false positives. Transthoracic echocardiography, cardiovascular magnetic resonance and computerized tomography are the most frequently used imaging methods, allowing for morphologic and functional evaluation. Patients with LVNC present a significantly higher risk of fatal arrhythmias - requiring implantable cardioverter-defibrillator (ICD) - death, heart failure and cardiac transplantation. Patients with these presentations have an increased risk of death in 6 years of 47-75%. Furthermore, a higher prevalence of this pathology was observed in other genetic conditions, such as Ebstein's anomaly (15%) and aortic coarctation (3%), among others. A definitive treatment is not presented in any guidelines, and the orientation is to avoid and treat heart failure, thromboembolism and arrhythmias caused by the condition. Conclusion: The lack of sufficient knowledge of its physiopathology, the still restricted understanding of the genetics and the diagnostic challenges are obstacles in fully understanding LVNC, and further studies are required to better characterize this pathology. 109976 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Catheter Ablation in Early Rhythm Control in Patients with Atrial Fibrillation and Heart Failure with Reduced Ejection Fraction: A Systematic Review ANA KAROLINA BENTO DA SILVA1, Lucas Caetano da Silva1, Gustavo Gomes Santiago1, Leonardo Torreao Bezerra Cavalcanti1, Glaudir Donato Pinto Junior1, Livia Farias de Holanda Furtado1, Manasses Almeida de Franca1, Andressa Alves de Carvalho1, Wanessa Alves de Carvalho1, David Cesarino de Sousa1, Evellyn Pereira de Melo1, Marcela Lukerli Araujo Paulina da Silva1 (1) Universidade Federal da Paraiba Introduction: The association between atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) increases the risk of cardiovascular complications. The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4) demonstrated that early rhythm-control therapy generated favorable outcomes in patients with AF. Objective: This study sought to investigate whether there is benefit in catheter ablation (CA) based rhythm-control in patients with AF and HFrEF compared to other strategies. Methods: Clinical trials and randomized clinical trials found in the Medline, Embase, Cochrane, and Scopus databases that analyzed the use of CA in early rhythm-control in patients with HFrEF and AF -- paroxysmal, persistent or diagnosed in less than 12 months -- between 2012 and 2022 were included. Articles that contemplated long-standing persistent AF and did not indicate left ventricular ejection fraction or New York Heart Association (NYHA) functional class were excluded. An independent review was performed by three authors following the PRISMA protocol. Results: Of the 41 articles found, 4 were selected for this review. Of these, 3 articles chose a similar primary outcome -- composition of cardiovascular events, including death and hospitalization due to worsening of HF. Nevertheless, the results were discordant. In the CASTLE-AF trial, CA altered primary outcome and death and hospitalization for HF. In the CABANA trial, however, there was a significant variation only in isolated criteria. In a subanalysis of EAST-AFNET 4, Rillig et al., 2021 indicates that the early rhythm-control therapy positively impacted primary outcomes, but that CA alone showed no significant difference compared with the antiarrhythmic control strategy. Jones et al., 2013 chose to approach AF from a functional perspective -- VO2max and impacts on quality of life after CA, with favorable results after 3 months of the procedure. Conclusion: Although CA is a promising alternative for early rhythm-control therapy in patients with AF, there is no precision on cardiovascular morbidity and mortality outcomes when HFrEF is associated. The variability of results found in this review indicates the need for even more robust future clinical trials in order to outline the possible benefit of the optimized indication of CA in this group. 109981 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION The Role of Cardiopulmonary Exercise Testong (Cpet) in Predicting Morbidity Outcomes in Grown-Up Congenital Heart (Guch) Disease - a Preliminary Study LAIZ TEIXEIRA PONTES1, Alice Cunha Darze1, Pamela Castro Pereira1, ALmir Ferraz1, Ana Luiza Guimaraes Ferreira1, Carlos ALberto Cordeiro Hossri1, Carolina Christianini Mizzaci1, Flavia Bernardes Morais1, Guacira Grecca1, Susimeire Buglia1, Ediele Carneiro Brandao1, Rica Dodo Delmar Buchler1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Given the advances in diagnosis and clinical-surgical therapies, congenital heart defects are increasing their prevalence in the adult population. Yet, there is still no consensus on the best way to follow up with these patients. Among the validated tools for monitoring patients with heart disease, the Cardiopulmonary Exercise Test (CPET) plays an important role. However, the use of this test for monitoring the population of Grown Up Congenital Heart (GUCH) still lacks studies. This study aimed to assess the correlation between ergospirometry variables and the severity of the GUCH population measured by echocardiographic aspects. Methods: A retrospective cohort with 248 GUCH (Table 1) over 18 years old, was referred to CPET, from 2015 to 2021, in a tertiary hospital in the state of Sao Paulo. Patients were sequentially included, and those in functional class IV or with contraindications to CPET were excluded. Ergospirometry variables were analyzed in association with ventricular function - estimated by echocardiogram in the same period. Results: Most patients were in functional class I and II (86.3%). In the echocardiographic findings, 40% had pulmonary hypertension and almost all had preserved left ventricle function. The CPET showed a median VO2 peak around 69% of predict. Other parameters are summarized in Table 2. CPET variables were able to stratify the severity of GUCH, mainly by pulmonary hypertension. Comparing CPET data and imaging diagnosis, VE/VCO2 slope >32 and OUES <60% were related to the presence of pulmonary hypertension. Conclusion: The CPET is an important resource for prognostic and diagnostic definition in the evolution of GUCH patients. 110000 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Evaluation of the Rate of Arterial Hypertension Control in the Basic Health Strategy: A Systematic Review GUSTAVO GOMES SANTIAGO1, Ana Karolina Bento da Silva1, Leonardo Torreao Bezerra Cavalcanti1, Evellyn Pereira de Melo1, Marcela Lukerli Araujo Paulina da Silva1, Andressa Alves de Carvalho1, Wanessa Alves de Carvalho1, David Cesarino de Sousa1, Glaudir Donato Pinto Junior1, Livia Farias de Holanda Furtado1, Manasses Almeida do Nascimento1, Lucas Caetano da Silva1 (1) Universidade Federal da Paraiba Introduction: Systemic Arterial Hypertension (SAH) is a multifactorial condition defined by persistent elevation of blood pressure (BP). It is considered an important public health problem due to its high prevalence and an independent cardiovascular risk factor. Studies show higher morbidity and mortality from cardiovascular disease (CVD) among individuals with high BP. Between 2008 and 2017, 667,184 deaths attributable to SAH were estimated in Brazil and it is estimated that more than 30% of Brazilians have SAH. However, despite the high prevalence, it is considered that the control of SAH in Brazil is still poor. Objective: To assess the rate of control of SAH at the level of the Basic Health Strategy and the socioeconomic indicators of cardiovascular risk and mortality. Methodology: For the production of this integrative literature review, articles were searched in PubMed and SciELO databases, using the following descriptors: "Primary Health Unit" and "Hypertension". The following inclusion criteria were used: articles from 1996 to 2020; studies in English and Portuguese. The following exclusion criteria were used: studies that did not correlate the two descriptors; published outside the period from 1996 to 2022; studies not available in English, Spanish and Portuguese. 732 articles were found, 5 of which included randomized double-blind studies, literature review and clinical trials. Results: BP values were considered controlled in most studies (systolic blood pressure lower than 140 mmHg and diastolic blood pressure lower than 90 mmHg). However, some studies have adopted different values for BP control and different BP targets depending on the target group that hypertensive patients are in (elderly, diabetic, post-infarction, post-stroke, etc). The rate of SAH control at the primary health care level in Brazil, according to the studies evaluated, ranged from 20 to 53.9%. There was a great diversity of techniques adopted to measure the control rate, such as repeated BP measurements by different devices (oscillometric, auscultatory, etc.), active search in medical records and in databases. There was variation in the BP control rate according to the Brazilian states. Conclusion: There is a wide variation in the frequencies of SAH control rates. Consequently, further studies are needed for a better care strategy and reduction of cardiovascular morbidity and mortality. 110036 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Initial Experience of the Telehealth Center at the University Hospital of the Federal University of Piaui: Results from the Tele-Icu PATRYCK ARAUJO DANTAS DA SILVA1, Carlos Eduardo Batista de Lima1, Igor Denizarde Bacelar Marques1, Victor Eulalio Campelo1, Maria Susane Filgueira Barreto Ferreira1, Lucas Cortez Macedo1, Lina Madeira Campos Melo1, Alessandro Aita1, Ginivaldo Victor Ribeiro do Nascimento1, Paulo Marcio Sousa Nunes1 (1) Hospital Universitario da Universidade Federal do Piaui Introduction: Teleconsulting activities in remote intensive care units can improve the quality of care and health indicators in regions with less access to specialists. In times of the Covid-19 pandemic, this technology has been increasingly used in assistance actions in health services. Objective: To evaluate the clinical-demographic profile and the remote coverage of the telehealth service in the studied population. Methods: The ICU telehealth system consists of a base at the HU-UFPI and a analysis system called Gestor Saude that keeps the peripheral units connected in a teleconsultation platform, allowing simultaneous consultation with the on-duty physician in the remote unit. From August 2020 to February 2022, all data from teleconsultations in intensive care performed in the telehealth service of the Hospital Universitario of the Federal University of Piaui provided at the Floriano, Bom Jesus, Sao Raimundo Nonato and Parnaiba units were evaluated. Data on age group, sex, unit of origin of care and clinical diagnosis of patients were analyzed. Other variables included were the use of vasoactive drugs and the need for oxygen therapy. The results were tabulated in an Excel spreadsheet and presented in a descriptive way. Results: 2114 teleconsultations were carried out in the ICU, most of them in male patients over 80 years old, followed by the age group from 60 to 69 years old. Most diagnoses were sepsis, with a lower proportion of patients with Covid-19 infection and traumatic brain injury. Among the centers assisted, the one with the highest number of consultancies was the city of Floriano, which already had a link with the UFPI due to a similar service previously implemented. Patients from 68 cities in Piaui were assisted, demonstrating the coverage of the project. Conclusion: In this initial experience of the telehealth center in the ICU of the HU UFPI, we observed the shortcomings that places far from large health centers present, such as, for example, a shortage of specialists in intensive care, internal operational difficulties and complementary exams. The frequent contact with HU-UFPI specialists helped to improve processes and transmit the quality culture that has been proven to improve results in the ICU. We encountered technical difficulties during implementation, but they did not prevent the process from progressing in most centers. 110040 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSICAL EDUCATION Comparison of Cardiac Chronotropic Response of Cardiopathes Participating in Cardiac Rehabilitation During Endurance Training and Resistance Training RENATA MARIA BEGNI AFONSO1, Daira Karoline Silva de Sousa1, Thiago Nascimento dos Santos1, Juliana Magalhaes Santos2, Rafaela Rodrigues de Sousa2, Thaiane Campos Martins2, Luana Cristina Pereira Pacheco11, Lucas Heitor Moura2, Renato Luiz de Alvarenga3 (1) Instituto Carlos Chagas; (2) Cardioclin; (3) UFRJ Introduction: Resistance training in Cardiac Rehabilitation is still underused, even though the low strength and muscle mass levels of this population. This is due to the fear of a greater cardiovascular risk in relation to this model, although it is already understood in the literature that heart rate (HR) is more responsive to the time of muscle stimulus than the applied load, presenting higher mean values in resistance training than in resistance training. Objective: To compare the HR behavior of cardiopaths trained during resistance and endurance exercise. Methods: Eighteen cardiac patients (65 +- 12,9), practitioners of Cardiac Rehabilitation, clinically stable and medicated with beta adrenergic blockers, performed their usual training on a horizontal exercise bike Movement RT230 (Brazil), between 10 and 15 minutes and 40% and 80% of reserve FC. Soon after, they performed resistance training in the Buick leg extension (Brazil): 10 submaximal repetitions and after 2 min of interval, 5 more submaximal repetitions with the addition of 20% of the previous load. HR was measured using the Polar Verity Sense transmitter tape (Finland), before and shortly after each exercise model, and a HR (final - initial) was calculated. For statistical analysis, the Friedman test and the Bonferroni post-test were used, with p < 0.05. Results: Table 1 shows the highest HR value for the group of exercise bike compared to the others, which was confirmed with p = 0.018 and p = 0.000 when compared to 10 repetitions and 5 repetitions, respectively. Conclusion: A greater spread of resistance training is encouraged in Cardiac Rehabilitation programs, in order to provide eligible cardiac patients with all the cardiovascular and peripheral benefits that resistance training makes possible. 110050 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Arterial Stiffness Associated with Sympathetic Hyperactivity in Obese Individuals with Moderate to Severe Obstructive Sleep Apnea SAMANTA MATTOS CARDOSO1, Samanta Mattos Cardoso1, Michelle Rabello Cunha1, Marcia Regina Simas Torres Klein1, Mario Fritsch Toros Neves1 (1) Universidade do Estado do Rio de Janeiro Introduction: Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. The presence of OSA and obesity may have synergistic effects on the progression of cardiovascular disease. Objective: To evaluate sympathetic tone and vascular disease in obese patients with moderate and severe OSA. Methods: Individuals of both sexes, aged 40-70 years and body mass index (BMI) >=30 and <40 kg/m2, submitted to assessment of heart rate variability (HRV), central parameters by Mobil-O-Graph and carotid ultrasound. The sleep study was performed through a portable home sleep test device (WatchPAT). Results: Patients (n = 76) were divided into two groups based on the apnea-hypopnea index (AHI): mild-absent (MA) group (AHI <15 events/h, n = 30) and moderate-severe group (MS) (AHI >=15 events/h, n = 46). The mean age was higher in the MS group (50 +- 6 vs 54 +- 8 years, p = 0.022) and BMI was similar (35 +- 3 vs 34 +- 3 kg/m2, p = 0.239). As expected, the MS group presented higher oxygen desaturation index (3.4 +- 2.2 vs 17.6 +- 12.7 events/h, p < 0.001) and respiratory disturbance index (12 +- 4 vs 33 +- 14 events/h, p = <0.001). Systolic blood pressure (119 +- 13 vs 127 +- 15 mmHg, p = 0.004), pulse pressure (41 +- 8 vs 46 +- 10 mmHg, p = 0.026), cardiovascular risk (6.4 +- 3.8 vs 11.9 +- 9.5%, p = 0.012) and cardiometabolic age (48 +- 6 vs 52 +- 9 years, p = 0.033) were significantly higher in the MS group. The SD2/SD1 ratio (1.4 +- 0.4 vs 1.7 +- 0.6, p = 0.064) and the low frequency/high frequency (LF/HF) ratio (0.85 +- 0.51 vs 1.53 +- 1.76, p = 0.051) were higher in the MS group, although not reaching statistical significance. The pulse wave velocity (PWV) (6.9 +- 0.7 vs 7.7 +- 1.2 m/s, p = 0.003), normalized PWV (7.1 +- 0.8 vs 7.7 +- 1.6 m/s, p = 0.046), PWV adequacy (-0.14 +- 0.42 vs 0.07 +- 0.37, p = 0.030), vascular age (47 +- 6 vs 53 +- 9 years, p = 0.005), mean carotid intima-media thickness (cIMT) (0.59 +- 0.08 vs 0.66 +- 0.13 mm, p = 0.008) and maximum cIMT (0.64 +- 0.09 vs 0.71 +- 0.15 mm, p = 0.015) were significantly higher in the MS group. PWV was significantly correlated with LF/HF ratio (r = 0.611, p = <0.001) in the MS group. Conclusion: In this sample of obese individuals, moderate to severe OSA was associated with sympathetic hyperactivity and evidence of accelerated vascular aging with arterial stiffness and subclinical atherosclerosis. 110944 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Multidisciplinary Heart Transplant Outpatient Clinic: A Pilot Study of Pharmaceutical Care LIDIA EINSFELD1, Leticia Orlandin1, Jacqueline Kohut Martinbiancho1, Thalita da Silva Jacoby1, Simone Dalla Pozza Mahmud1, Nadine Clausell1, Livia Adams Goldraich1 (1) Hospital de Clinicas de Porto Alegre, Brasil. Background: The role of clinical pharmacists as part of multidisciplinary teams for solid organ transplant care has been discussed worldwide. Particularly, heart transplant recipients have a complexity of medication regimens, which greatly impact on both patient and transplant program outcomes. Aim of the study: To evaluate the participation of clinical pharmacists in the multidisciplinary heart transplant outpatient clinic through the identification of drug therapy problems (DTPs) and interventions in the pharmacotherapy based on pharmacist recommendations. Methods: In this descriptive pilot study, pharmacists provided direct patient care in the weekly heart transplant clinic from January to December 2021. Each patient seen at a pharmacist consult visit received a comprehensive assessment using a systematic drug therapy review process . Pharmacist's activities were documented in electronic charts, and data, collected prospectively. DTPs and pharmacist interventions were classified according to the PCNE. Results: A total of 207 clinic visits to 70 patients were performed and 223 DTPs identified, leading to a median of 2 interventions per consult visit. In more than a third of the opportunities, patients received a dose adjustment recommended by the pharmacist (39.2%). Frequent interventions included laboratory monitoring (15.9%) and medication deprescribing (9.3%). Immunosuppressants were the drugs most commonly involved (35.6%), followed by electrolyte supplements and antihypertensive agents (15.1% and 13.7%, respectively). Conclusion: Our study was the first to describe pharmaceutical care of ambulatory heart transplant recipients in Brazil. Pharmacist-led interventions can potentially contribute to the management of challenging post-transplant pharmacotherapy. 110056 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Microcosting of Intravenous Diuretic use Strategy in Day Hospital for Patients with Heart Failure DAYANNA MACHADO PIRES LEMOS1, Ana Paula Beck Da Silva Etges3, Nadine Oliveira Clausell2, Livia Adams Goldraich1 (1) HOSPITAL DE CLINICAS DE PORTO ALEGRE; (2) UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL; (3) Instituto de Avaliacao de Tecnologias em Saude Background: The use of intravenous (IV) diuretics to treat congestion in outpatients with heart failure (HF) seems to be as effective in maintaining clinical stability as usual hospital therapy, and can potentially reduce costs. Objective: To assess the cost of a day hospital strategy for IV diuretic in patients with HF. Method: Cost study was carried out in a public and university hospital in Brazil. Time-driven Activity-based Costing was applied to calculate the total cost of services and their composition per patient, in addition to an exploratory analysis of a day hospital schedule for HF. Results: Data of 68 sessions of IV diuretic from 20 patients during 2020 were analyzed. On average, 80 mg of furosemide was administered in sessions lasting 39 minutes; 11 patients had a single session of IV diuretic, while 2 patients underwent 19 and 21 sessions each. The annual median cost per patient was US$ 34 (min. US$ 30; max. US$ 515) . Costs was attributed to professionals (58%), exams (23%), physical structure of the unit (10%), consumables (5%) and medicines (3%). A hypothetical schedule with 48 monthly sessions would cost US$ 1,464. Conclusions: This study contributes with novel information involving microcosting of a day hospital strategy for IV diuretic treatment in patients with HF. This data can generate subsidies for the incorporation of such potentially cost-saving strategies in a sustainable manner. 110183 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Association of Cyp11B2 Rs3097 C> T and Rs3802228 G> a Polymorphisms with Reduced Ejection Fraction Heart Failure in a Population of Mixed Ancestry GIZELLA DA CUNHA RODRIGUES1, Felipe Neves de Albuquerque2, Gustavo Salgado Duque2, Ariene Brito do Amaral2, Yasmin Lemos Rollemberg Cruz Machado1, Marcelo Imbroinise Bittencourt2, Denilson Campos de Albuquerque2, Dayse Aparecida da Silva1, Ricardo Mourilhe-Rocha2 (1) Laboratorio de Diagnostico por DNA, Instituto Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil; (2) Hospital Universitario Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil Introduction: Heart failure (HF) is a clinical and multifactorial syndrome that affects approximately 26 million people around the world. HF is generally subclassified according to the left ventricular ejection fraction (LVEF) into 3 categories: HF with preserved ejection fraction (LVEF >= 50%), HF with mid range ejection fraction (LVEF 41%-49%), and HF with reduced ejection fraction (HFrEF, in which the LVEF is <=40%). The pathophysiology of HFrEF is complex, and it is usually preceded by direct injury to the myocardium or a previous disease that leads to reduced ventricular contraction. The renin-angiotensin-aldosterone system (RAAS) is an important target to study the pathophysiological mechanisms involved in HF development. Objective: The main objective of this study was to determine the association of rs3097 (C>T) and rs3802228 (A>G) single nucleotide polymorphisms, present in CYP11B2 gene, with HFrEF. Ancestry informative markers of polymorphisms insertion/deletion were also determined to identify individuals' ancestry and exclude spurious associations regarding the selected genetic targets. Methods: A total of 185 unrelated patients with HFrEF were selected, in addition to 124 unrelated volunteers without cardiovascular diseases. Data provided by HGDP-CEPH reference, containing profiles from African, European, and Native American populations were used to perform ancestry analysis estimations. Results: The control and patient groups were aligned according to gender (HFmen = 66% versus Cmen = 55%, p = 0.06) and age (HF = 50.6 +- 11.6 versus C = 48.5 +- 8.9, p = 0.09). A statistically significant association can be observed in relation to the genotypic frequencies of rs3097 C>T between HF group versus controls when using the codominance (p = 0.0031), dominance (p = 0.0007) and overdominance (p = 0.0035) models. There were not observed any association regarding the rs3802228 A>G polymorphism. The analyses involving the ancestral relationships between the groups are still being carried out. Conclusion: The preliminary results suggest a possible link between the T allele of CYP11B2 rs3097 C>T polymorphism and HFrEF. 110087 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSICAL EDUCATION Health Education for Rheumatic Heart Disease Prevention and Early Detection at a Highly Prevalent Peri-Urban Community in Mozambique EDNA SUSANA LOPES LICHUCHA1, Adjine Mastala Fumo1, Andrea Neves3, Euridsse Amade1, Keila Jamal4, Karen Sliwa5, Ana Mocumbi1 (1) Instituto Nacional de Saude (INS), Maputo - Mozambique; (2) Universidade Eduardo Mondlane (UEM), Maputo - Mozambique; (3) Hospital Geral Jose Macamo, Maputo - Mozambique; (4) Mozambique Institute for Health Education and Research, Maputo - Mozambique; (5) Cape Heart Institute, University of Cape Town - South Africa Abstract Rheumatic Heart Disease (RHD) usually follows repeated episodes of acute rheumatic fever (ARF), which complicates untreated group A streptococcus (GAS) infections in susceptible individuals. RHD is a neglected disease that affects socially and economically disadvantaged young people in endemic areas, with a more malignant course in Africa, where it is an important cause of premature mortality, including indirect maternal mortality. We report an approach to increase awareness and promote health education of high-risk populations in a low-income setting. Methods: The activities were implemented in peri-urban Maputo, Mozambique from February/2019 to February/2020. We trained 21 maternal health professionals in RHD screening and implemented a bi-monthly joint cardio-obstetric clinic involving health education sessions run by six patients living with RHD (PLRHD) trained as peer-educators. At Matchikitchiki Primary School we painted outdoor RHD educational walls (September-October/2019) and trained 40 teachers to support RHD book coloring and video workshops. Results: The Cardiac-Obstetric Clinic assisted 127 women, of which 21 (17.3%) with RHD. Six trained PLRHD delivered 17 health education sessions to 127 patients. We trained 864 children (375 colored the book), 357 watched and discussed the educational video, and 232 were involved in outdoor activities using the RHD wall). Conclusions: Training of teachers, maternal health professionals and PLRHD allows creation of awareness and early detection of RF/RHD in high-risk populations. These strategies may foster decentralization of early diagnosis and prevention of RF/RHD in highly prevalent communities in Africa. 110129 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Ecg Protocol: Evolution of Care Times for Patients with High Risk Acute Coronary Syndrome in Emergency Rooms in Salvador-Ba RAYLANE MARQUES DE BARROS CRUZ1, Pollianna de Souza Roriz1, Daiane Dias de Jesus1, Marta Gabriela Moura Lopes1, Tatiana de Sena Leitao1, Rilary Silva Sales1, Shirley Casais Reis1 (1) Servico de Atendimento Movel de Urgencia - SAMU The electrocardiogram (ECG) is essential for the stratification of Acute Coronary Syndromes (ACS), in which the finding of ST-segment elevation reflects coronary occlusion and indicates the need for reperfusion therapies. In order to optimize the door-to-ECG time, the team responsible for the evaluation of cases with high risk ACS in the city of Salvador-BA, entitled "Protocol-IAM" (P-IAM), developed the "ECG Protocol", easy to apply in the risk classification - implemented in the Pre-hospitalar Emergency Care Units (UPA) of the municipality since July/2020. The time elapsed between the ECG and the P-IAM trigger (ECG-trigger) is also relevant as it starts P-IAM attending. Objective: To compare the door-to-ECG and ECG-trigger with high-risk ACS in patients at the UPA in the city of Salvador-Ba before and after promoting ECG Protocol in the city. Method: This is a cross-sectional and descriptive study; The P-IAM database was used, referring to users diagnosed with high-risk ACS treated at the UPA in Salvador, between 03/04/2017 to 12/31/2021. The analyzed data were the mean and median (minutes) of the Symptom-Admission, and ECG-Trigger times; total number of patients on reperfusion therapy. Results: A total of 1,679 patients were attended by the P-IAM accessing the public health system through the UPA during this period. Of these, 1,416 (84%) were diagnosed with ST-segment Elevation Myocardial Infarction (STEMI), with an increase of 58% comparing 2017 to 2021, followed by reperfusion therapies (171 in 2017 to 310 in 2021). Median times are seen in figure 1. Conclusion: After the disclosure of the ECG Protocol, there was an increase of P-IAM team activations; greater sensitivity of the emergency network in identifying patients with STEMI, as beneficiaries of the program. 110139 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION The use of Oral Anticoagulants and Strategies to Improve its Adherence Among Outpatients with Heart Disease ANDRESSA TEOLI NUNCIARONI1, Gabriella Sena do Nascimento Santos2, Renata Flavia Abreu da Silva1 (1) Alfredo Pinto Nursing School, Federal University of the State of Rio de Janeiro - UNIRIO; (2) State University of Rio de Introduction: Among the drugs that make up the treatment of cardiovascular diseases, the class of oral anticoagulants (OAC) stands out. In Brazil, the main representative of the class is sodium warfarin, due to its low cost and distribution by the Brazilian Unified Health System. The treatment with OAC is complex and requires specific care related to prescription, guidelines for use, taking the drug, and monitoring of efficacy. Thus, adherence to treatment is necessary to ensure its full effectiveness and achieve positive prognosis. Objectives: To identify OAC adherence among outpatients with heart disease and to recognize strategies for increasing adherence among non-adherents. Methods: Cross-sectional quantitative study, conducted in the Anticoagulation Outpatient Clinic of a large Cardiology Federal Hospital, located in Rio de Janeiro, Brazil. Data collection occurred from March to July 2021. We included 76 patients in outpatient follow-up, older than 18 years of age, using OAC. Adherence to OAC was measured through the Instrument for Global Assessment of Medication Adherence (IAGAM), already validated for Brazilian culture and for the assessment of adherence among patients using OAC. Data was analyzed through RStudio Software. The research was approved by the local ethics committee under evaluation number 4.531.072 of 09/02/2021. Results: Considering only medication adherence rate, the participants had averages above 99% when asked about taking the medication on the day, week, and month prior to data collection. However, when associating the number of pills taken with the care required, only 86.84% implement adequate care. These numbers represent the overall adherence measured by IAGAM. Strategies reported by participants to increase adherence were use of an alarm clock; placing the prescription in a visible place, such as the refrigerator and bedside table; keeping the medicine box next to bed, with the schedule written on it; taking the medication associated with routine activities, such as before going to work; family members being responsible for administering the medication, thus remembering the schedule and the correct dose. Conclusions: The assessment of adherence to OAC should consider, in addition to taking the pills, the care needed to improve the drug efficacy. Strategies to enhance OAC adherence might target the underlying care. 110182 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION St-Segment Elevation and T-Wave Inversion Confined to V1-V4 in Young Soccer Players: Prevalence and Differences from Afro-Brazilians to Ghanaians FILIPE FERRARI1, Henrique C. da Silva2, Artur H. Herdy3, Luiz G. M. Emed4, Felipe E. F. Guerra5, Haroldo C. Aleixo6, Guilherme D. Dilda7, Fernando Bassan8, Anderson D. da Silveira9, Ricardo Stein1 (1) Hospital de Clinicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brazil; (2) Universidade do Estado do Para (UEPA), Belem, PA - Brazil; (3) Instituto de Cardiologia de Santa Catarina, Santa Catarina, SC - Brazil; (4) Hospital Cardiologico Costantini, Curitiba, PR - Brazil; (5) Clinica Biocardio, Natal, RN - Brazil; (6) Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG - Brazil; (7) Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (USP), Sao Paulo, SP - Brazil; (8) Universidade Estadual do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brazil; (9) Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS - Brazil Introduction: Afro-Caribbean athletes may present some peculiarities in resting 12-lead electrocardiogram, such as T-wave inversion (TWI) confined to V1-V4 preceded by ST-segment and J-point elevation. However, the prevalence of this finding in young Afro-Brazilian football players (YABFP) is unknown. Purpose: To compare the prevalence of 'domed' ST-elevation and TWI in V1-V4 among YABFP with young Ghanaian black football players (YGBFP). Methods: A visual analysis was performed, as the data from the YABFP were raw data and those from Ghana were aggregated data. A forest plot was constructed with the point estimate and 95% confidence intervals. Results: 668 YABFP (mean age: 21 years) and 159 YGBFP (mean age: 19 years) were evaluated and compared. The average height and weight were similar (178 cm and 73 kg for YABFP, and 175 cm and 68 kg for Ghanaian players). Ghanaians had a significantly higher prevalence of 'domed' ST-elevation and TWI in V1-V4 than YABFP (16.7% versus 2.4%, respectively). Conclusion: YABFP presents a low prevalence of 'domed' ST-elevation combined with TWI in V1-V4, and African players had an almost 8-fold prevalence of this finding compared to Afro-Brazilian players. 110181 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Prevalence of Abnormal Electrocardiographic Findings in a Brazilian Cohort of Young Football Players: B-Pro Foot ECG Pilot Study FILIPE FERRARI1, Henrique C. da Silva2, Luiz G. M. Emed3, Artur H. Herdy4, Guilherme D. Dilda5, Felipe E. F. Guerra6, Haroldo C. Aleixo7, Fernando Bassan8, Frederico P. L. Coimbra9, Mateus F. Teixeira10, Anderson D. da Silveira11, Ricardo Stein1 (1) Hospital de Clinicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brazil; (2) Universidade do Estado do Para (UEPA), Belem, PA - Brazil; (3) Hospital Cardiologico Costantini, Curitiba, PR - Brazil; (4) Instituto de Cardiologia de Santa Catarina, Santa Catarina, SC - Brazil; (5) Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (USP), Sao Paulo, SP - Brazil; (6) Clinica Biocardio, Natal, RN - Brazil; (7) Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG - Brazil; (8) Universidade Estadual do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brazil; (9) Hospital de Urgencias de Goiania, Goiania, GO - Brazil; (10) Clube de Regatas Vasco da Gama, Rio de Janeiro, RJ - Brazil; (11) Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS - Brazil Introduction: A 12-lead resting electrocardiogram is a useful tool for diagnosing pathological conditions in athletes. The prevalence of electrocardiographic abnormalities in young Brazilian football players (YBFP) is unknown. Purpose: To describe the prevalence of abnormal electrocardiographic findings in YBFP based on the "2017 International Criteria for Electrocardiographic Interpretation in Athletes". Methods: Cross-sectional/descriptive study. Intra-group differences were estimated by linear models or binomial and multinomial logistic regressions. Results: 3.490 athletes from 41 Brazilian clubs, aged 15-35 years (median: 19 years) were evaluated. 1.668 were Caucasians, 1.154 were Mixed-race (MR), and 668 Afro-Brazilians (AB). T-wave inversion in the inferior leads (4%), high lateral leads (0.5%), V5 (2.4%), V6 (2%), and V5-V6 (2%) were identified. Prolonged corrected QT interval (0.1%), QRS >=140 ms (0.1%), premature ventricular contractions (0.2%), PR interval >=400 ms (0.03%), Wolff-Parkinson-White pattern (0.06%), and a suggestive case of a type 2 Brugada pattern were also observed. Other abnormalities were not observed. Overall, 216/3.490 (6%) YBFP had electrocardiographic changes considered to be abnormal. Conclusion: This is the first large electrocardiographic cohort of YBFP described. In it, a prevalence of approximately 6% of abnormal findings was identified. Further evaluation in all these cases is indicated. 110364 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Clinical and Epidemiological Behavior of Cardiopatic Pregnant Women in a Cardiological Reference Hospital in the Brazilian Amazon LUCIANNA SERFATY DE HOLANDA1, Maria Elizabeth Navegantes Caetano Costa1, Maria Talita Rodrigues Pinto Campos1, Laise Braga Vieira1, Vitor Bruno Teixeira de Holanda1, Ivy de Almeida Cavalcante e Silva1 (1) FUNDACAO HOSPITAL DE CLINICAS GASPAR VIANNA DO PARA Background: Studies on heart disease in pregnant patients show that it is the main indirect cause of deaths of pregnant women who are in the pregnancy-puerperal cycle. In addition, heart disease can lead to other problems that depend on the clinical and epidemiological state presented during pregnancy. Objectives: To describe the clinical and epidemiological behavior of pregnant with heart disease registered at Hospital das Clinicas Gaspar Viana, from January 2017 to December 2019. Methods: An epidemiological, retrospective and cross-sectional study, by analyzing the medical records of 133 pregnant women with heart disease admitted to HCGV in the aforementioned period. Excel 2007 and Bioestat 5.3 software were used for descriptive statistics; the results were evaluated using the categorical variables of the sample acquired by the G and Chi-Square Adherence Tests and G and Chi-Square Independence Tests. Results: There was no difference between the age groups of the patients, where 81.2% did not have a personal morbid history; the most frequent diagnosis among the others was atrial septal defect with 14.3%. 80.5% are aware of their heart disease and are followed up. In turn, the functional class with the highest proportion was NYHA I with 72.2%. Finally, 60.2% had no problems with pregnancy, childbirth and postpartum. At the time of delivery, a statistically significant majority (*p = 0.0003) of patients were between 35 and 39 weeks of gestation (66.9%). Cesarean delivery was the one with the highest proportion (70.7%) and statistically significant (*p = 0.0008), in relation to vaginal delivery (27.1%). The majority of live births were statistically significant (*p < 0.0001). Conclusions: This study is relevant because due to the scarcity of information about heart disease in pregnant woman in the State of Para, considering that each one pregnant presents peculiarities, mainly on maternal and perinatal results or clinical and epidemiological profile of then. 110370 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY The Effect of Statin Therapy on the Prognosis of Patients who Underwent Transcatheter Aortic Valve Implantation (Tavi) BRENDA GABRIELE SMANIOTTO RAULIK1, Mateus de Miranda Gauza2, Rodrigo Ribeiro e Silva2, Julia Opolski Nunes da Silva2, Joao Pedro Ribeiro Baptista2, Caroline Figueiredo da Silva2, Marcelo Pitombeira de Lacerda2, Gibran da Costa Reis3 (1) Universidade Positivo; (2) Universidade da Regiao de Joinville; (3) Hospital Regional Hans Dieter Schmidt Introduction: In many cardiovascular diseases and procedures, statin therapy has been associated with a reduction in cardiovascular risk for future events. However, the effect of statin therapy for patients undergoing TAVI is not well documented and there are no randomized clinical trials evaluating this association. Considering the long-term mortality after TAVI not to be very satisfactory, it Is of great interest to find alternatives to reduce mortality after this procedure. Objetive: Evaluate the prognostic factor associated with statin therapy in patients who underwent TAVI. Methods: A systematic review was caried out using three data bases: Medline, Embase and the Cochrane library. We included observational studies that evaluated major adverse cardiovascular events, death and major bleeding in patients using statin therapy prior to TAVI. The terms used in the search strategy included "tavi", "tavr" and "statin". We found an initial number of 140 articles published until April 2022. After exclusion of duplicates and other studies that did not fit our objectives, 15 articles were included in our analysis. Results: In our review, 15 observational studies were included in the analysis. From them, 7 studies reported a reduction in all-cause mortality and cardiovascular mortality in patients using statin therapy. 3 studies reported a dose-dependent reduction in long-term mortality, with 1 paper indicating no reduction in the short term with any intensity. Only 1 case-control study found no reduction in mortality in the long-term nor the short term. The effect on mortality may even extend to octogenarian population. Conclusion: Statin therapy appears to be related with a reduction in long-term mortality rates after TAVI procedure, in dose dependent manner. 110416 Modality: E-Poster Young Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Hospital Admission for Acute Rheumatic Fever and Investment in the Treatment of Pharyngotonsillitis in Brazil: Is There a Relationship? NATHALIA LIMA SCHRAMM DOS SANTOS1, Nathalia Lima Schramm dos Santos1, Lucas Santos Silva1, Isabele Carolina Tokumoto1, Rebeca Magalhaes Araujo1, Lucas de Almeida Santos Rocha Pereira1, Ana Layse de Sa Goncalves Torres1, Pedro Emanuel de Jesus Ferreira1, Fernando Gassmann Figueiredo1, Vanessa Arata Figueiredo1 (1) Universidade Estadual de Feira de Santana (UEFS) Introduction: Rheumatic Fever (RF) is a multisystemic disease that, although preventable, still represents a common sequel of pharyngotonsillitis (PT) caused by group A beta-hemolytic streptococcus. In Brazil, there are an estimated ten million cases of PT per year, of which thirty thousand culminate in cases of RF. Its clinical importance is due to the sequelae of this condition, with biological impacts, as it is the main cause of mitral stenosis in the country and also socio-economic impacts, as it is related to a third of the heart surgeries in Brazil. Objective: To analyze the relationship between hospital admission rates for acute rheumatic fever per 100,000 inhabitants and the ratio between hospitalization costs of patients with pharyngitis and acute tonsillitis over the total number of cases of hospitalization for rheumatic fever in Brazilian states in the periodo of January 2008 to May 2021. Method: This is an ecological epidemiological study, whose data were obtained from the DATASUS database and from estimates from the Brazilian Institute of Geography and Statistics for the year 2020. The data were tabulated in the Microsoft Excel program, in which the rates and measurements of the linear regression test were calculated (Pearson's correlation coefficient and p-value). Results: During the study period, there were 49,056 hospital admissions for acute rheumatic fever in Brazil. The age group from 40 to 69 years old stands out, which has the highest number of hospitalizations (n = 20,733). Among those under 20 years old, there is a range of 10 to 14 years old with 4,673 hospitalizations. After performing the correlation between hospital admission rates for acute rheumatic fever and the ratio of hospitalization costs of patients with pharyngotonsillitis by the total number of hospitalizations for RF, a significant negative correlation was observed (r = -0.4 and p = 0.03888). The analysis of the distribution of hospital admission rates by RF by state highlights Pernambuco with 68 admissions per 100,000 inhabitants; Goias with 50 and Ceara with 41. The correlation between the mortality rate and costs per hospitalization was also negative, although negligible (r = -0.2 and p = 0.03893). Conclusions: The results show a relationship between the low investment in the treatment of acute pharyngotonsillitis and the higher rates of hospitalization for rheumatic fever. 110420 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Diagnoses, Interventions and Nursing Outcomes in Immediate Postoperative Period of Cardiac Surgery in Adults: A Systematic Scoping Review MARYANNA CRUZ DA COSTA E SILVA ANDRADE1, Ana Carla Dantas Cavalcanti1, Juliana de Melo Vellozo Pereira Tinoco1, Isabelle Andrade Silveira1 (1) Universidade Federal Fluminense - UFF Introduction: Nurses working in cardiology intensive care units need to improve their knowledge about diagnoses, interventions and nursing outcomes of cardiac surgery patients. Despite, there are no studies that have mapped these concepts in immediate postoperative period context. Objective: To map diagnoses, interventions and nursing outcomes for adult patients in immediate postoperative period of cardiac surgery. Method: Scope review based on Joanna Briggs Institute manual and guided by Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SrC) carried out on bases: Biblioteca Virtual em Saude, Cochrane Library, EBSCO, Epistemonikos, Embase, National Institute Heath and Care Excellence, PMC, Pubmed, Scielo, Science.gov, Scopus e Web of Science. Data were mapped considering Population of adult cardiac surgery patients with sternotomy, in the context of immediate postoperative period and with concept of interest in diagnoses, interventions and nursing outcomes. Results: 23 studies were identified for extraction in the end of selection process. 70 diagnoses, 57 interventions and 47 nursing outcomes using standardized language were mapped, summarizing an unprecedented way the three essential components for the nursing process of this clientele. Five scales for pain assessment, three for neurological assessment, one for predicting patient outcome and one for measuring severity were also mapped. Conclusion: The steps of nursing process were presented in systematic way for the patient in the immediate postoperative period of cardiac surgery through diagnoses, interventions and nursing results representing the affected needs of this clientele. Thus, main implication of this review for nursing care is to guide nurses' critical thinking. 110482 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS The Impact of the Heart Team on Chronic Coronary Artery Disease: Long-Term Follow-Up LUHANDA LEONORA CARDOSO MONTI SOUSA1, Bruno Mahler Mioto1, Nilson Tavares Poppi1, Julio Yoshio Takada1, Luis Henrique Wolff Gowdak1, Carlos Augusto Homem de Magalhaes Campos1, Luis Roberto Dallan1, Amanda Mazetto1, Miguel Antonio Moretti1, Luiz Augusto Ferreira Lisboa1, LUIZ ANTONIO MACHADO CESAR1, Luciana Oliveira Cascaes Dourado1 (1) Instituto do Coracao (InCor) do Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) Introduction: The Coronary Heart Team (CHT) is based on shared decision-making, between of the non-interventional, interventional cardiologist and cardiac surgical. The focus of defining the best treatment in a individualized way, based in scientific evidence. It has class I recommendation, evidence level C guidelines. However, the impact of this intervention is still poorly understood. Objective: To assess the impact of the CHT decision: clinical treatment (CT) percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) in reducing primary composite outcomes: Acute Coronary Syndrome (ACS) and Cardiovascular Death (CV) and symptom improvement: angina class (CCS) and heart failure (HF) class in patients with chronic CAD according to the degree of agreement with the CHT. Methods: Prospective, single-center cohort study, mean follow-up of 41.1 +- 20.7 months. From a cohort of 500 patients discussed in CHT from 2015 to 2020, we evaluated 113 patients, whose final treatment (FT) was defined by the CHT of a tertiary hospital between august 2015 and november 2016. Fisher's exact test or the chi-square test was used. Student's t test for paired samples. The agreement was when estimating the Kappa coefficient, p < 0.05 indicated statistical significance. Stata/SE Program v.14.1. StataCorpLP, USA and SPSS 20.0. Results: The mean age was 62.6 +- 9.8 years, 62.8% were male, diabetic (63%) and a history of AMI in 53.1%. The mean EF was 49.7%. Angina CCS II-IV 57.2%, HF class II-IV 49.1%. They were multivessel in 65.6% and main left coronary >50% associated in 19.47%. There was agreement between the proposed treatment (PT) by the referral cardiologista and the CHT K = 0.19 and good agreement between the CHT and the FT K = 0.62. CABG was the predominant FT and with the highest agreement with the CHT 88.1%, followed by PCI (79.2%) p = 0.005. Total mortality was 10.2%, CV death 5.6% and ACS 27.7%. There was a higher incidence of primary composite outcome when PCI was performed in disagreement with CHT p = 0.001, no difference for the other strategies. In 72% of the cases, angina improvement occurred (p = 0.001). For HF class, only the cases in agreement with the CHT had an improvement of 74.4% p = 0.008. Conclusion: Final treatment in agreement with the CHT was associated with a lower incidence of primary composite outcome and significant improvement in long-term symptoms. 110487 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Acceleration/Ejection Time Ratio as a Predictor Factor of Aortic Valve Stenosis SARA ABOURADI1, Abouradi Sara1, Bendahou Hajar1, Mackonia Noel1, Tamir Mehdi1, Bennouna Ghali1, Habbal Rachida1 (1) CHU IBN ROCHD CASABLANCA Background: Several factors may contribute to higher risk in patients with presumably moderate AS. Acceleration time (AT) and ejection time (ET) increase in parallel with AS severity, however AT/ET ratio in identification of high-risk subjects among asymptomatic mild-moderate AS is unknown The aim of the present analysis was to investigate the association between higher AT/ET ratio and outcomes in mild-moderate AS. Methods: Were included all patients with asymptomatic patients with presumably mild-moderate AS followed at the hospital of Ibn Rochd cardiology departement service in casablanca from October 2017 to June 2021, Patients were grouped according to the optimal AT/ET ratio threshold to predict cardiovascular death and heart failure hospitalization. Outcome was assessed in Cox regression analyses, and results are reported as hazard ratio and 95% CI. Results: The mean age was 65 +- 10. Higher AT/ET ratio was significantly associated with lower systolic blood pressure(p = 0,02), lower left ventricular ejection fraction(p = 0,01), low flow (p = 0,02), and with higher left ventricular mass (p = 0,03) and higher peak aortic jet velocity (p = 0,01). AT/ET ratio >=0.34 had a higher risk of cardiovascular death and heart failure hospitalization (hazard ratio: 1.98 [95% CI, 1.50-3,8]). In patients with moderate AS, AT/ET ratio >0.36 was associated with higher rate for cardiovascular death (p = 0,01) and HF hospitalization (P = 0.035). Conclusions: In asymptomatic moderate AS higher AT/ET ratio was associated with increased cardiovascular morbidity and mortality. 110488 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Assessment of Myocardial Energetic Efficiency in Asymptomatic Aortic Stenosis SARA ABOURADI1, SARA ABOURADI1, NOEL MACKONIA1, HAJAR BENDAHOU1, SOUKAINA ZAHRI1, ABDNASSER DIGHIL1, RACHIDA HABBAL1 (1) CHU IBN ROCHD CASABLANCA Introduction: Low myocardial energy efficiency (MEE) is undoubtedly associated with left ventricular dysfunction (LV) of the myocardium. the objective of this study was to investigate the effect of MEE in patients with asymptomatic aortic stenosis (AS). Methods: Were included all patients with asymptomatic aortic stenosis followed at the hospital of Ibn Rochd cardiology departement service in casablanca from October 2017 to June 2021. MEE was calculated from Doppler stroke volume/([heart rate/60]) and indexed to LV mass (MEEi). Outcome was assessed in Cox regression analysis and reported as HR and 95% CI. Results: The mean age was 60 +- 14 years mean ejection fraction: 50 +- 9%; mean aortic valve area: 1.04 +- 0.45 cm2; MEEi <0.35 mL/s per gram was associated with increased cardiovascular mortality [HR 1,98 (95% CI 1.60-3.28)] (both p < 0.02). This relationship persisted after multivariate adjustment and in the subgroups including more severe AS, higher body mass index, lower ejection fraction and presence of hypertension. (p = 0.01). Conclusions: In patients with asymptomatic AS, Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis regardless of other associated factors. 110489 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Asymptomatic Aortic Stenosis: What to Choose between a Conservative Attitude or An Early Surgery SARA ABOURADI1, SARA ABOURADI1, HAJAR BENDAHOU1, NJIE MALICK1, AMRI MERYEM1, AZZOUZI LAILA1, HABBAL RACHIDA1 (1) CHU IBN ROCHD CASABLANCA Background: Aortic stenosis is a very common pathology, several studies lean towards rapid surgical management, The aim of the study the objective of the study is to determine the appropriate attitude between rapid or conservative surgery. Methods: Were enrolled all patients with asymptomatic patients with severe aortic stenosis (defined as an aortic-valve area of <=1 cm2 with either an aortic jet velocity of >=4 m per second or a mean transaortic gradient of >=40 mm Hg) followed at the hospital of Ibn Rochd cardiology departement service in casablanca from October 2017 to June 2021 Patients were classified according to early surgery or to conservative care according. The primary end point was death during or within 30 days after surgery. Results: The mean age was 65 +- 10 In the early-surgery group there was no operative mortality. The primary end-point event occurred in 3 patient in the early-surgery group (2%) and in 12 patients in the conservative-care group (14, 3%) (hazard ratio, 0.07; 95% confidence interval [CI], 0.03 to 0.24; p = 0.002). Death from another cause occurred in 7 patients in the early-surgery group (10,5%) and in 16 patients in the conservative-care group (19,06%) (hazard ratio, 0.22; 95% CI, 0.11 to 1,90, p = 0,02). Conclusions: Early surgical aortic-valve replacement has a significantly lower risk of operative mortality or death from cardiovascular causes during the follow-up period than conservative care among asymptomatic patients with severe aortic stenosis. 110490 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY Cardiotoxicity: Therapy for HER2+ in Patients Diagnosed with Breast Cancer in a Private Institution in the Amazon MARCELLO FACUNDO DO VALLE FILHO1, Marcello Facundo do Valle Filho1, Odilon Pereira Velho Filho1, Vanessa Mendes Moreira1, Thalita Giovana Diniz Silva1, Giovanna Piva1, Lia Mizobe Ono2, William Hiromi Fuzita2, Monica Regina Hosannah da Silva e Silva1 (1) Faculdade Metropolitana (FAMETRO); (2) Oncologia Sensumed e Instituto Sensumed de Ensino e Pesquisa Ruy Franca (ISENP), Manaus-AM. Introduction: Heart disease and cancer are the main causes of morbidity and mortality in the industrialized world. Breast Cancer is a heterogeneous disease with different prognoses, therapeutic protocols and treatment outcomes. Identification of HER2+ on immunohistochemistry and/or FISH indicates a need for targeted therapy with HER2+ receptor blockers. However, its use may be related to cardiotoxicity, which may be manifested by an asymptomatic decline in left ventricular ejection fraction (LVEF) and/or by the occurrence of symptomatic heart failure, diagnosed through echocardiography. One of the therapies involves pertuzumab (a monoclonal antibody) associated with trastuzumab (which can also be applied alone) and docetaxel, with improved overall and progression-free survival. Considering normal LVEF above 55%, a fall below 10% may be completely reversible, while in those above 10%, reversal may occur in 91% of cases. Even in the presence of cardiotoxicity, 70% to 80% of patients continue to receive targeted therapy. Method: Cross-sectional, observational, descriptive and retrospective study of 697 patients diagnosed with breast cancer at Oncologia Sensumed in the city of Manaus-AM where 69 patients with HER2+ were selected. Results: Of the 69 patients, 45 (65%) received transtuzumab monotherapy, with a mean of eight doses (minimum of 3 and maximum of 17) at 21-day intervals, 16 (23%) received combined triple therapy. All ejection fractions measured quarterly by echocardiogram were within the normal range, ranging from 61% to 75%. Eight patients (12%) did not use any of the three drugs due to previously diagnosed medium and high-grade heart failure. Conclusion: The assessment of LVEF and the presence of heart failure (HF) before starting treatment for breast cancer with HER2+ influences the therapeutic protocol and treatment outcome. In addition, maintaining a quarterly evaluation elucidates data that indicate maintaining, discontinuing or establishing new options for treatment of both cancer and reduced LVEF and HF. Therefore, even with cardiotoxic effects, therapy directed at HER2+ in breast cancers can bring benefits to the prognosis, provided that they are monitored and evaluated quarterly through echocardiography and anamnesis to identify symptoms. 110496 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Epidemiological Profile of Pediatric Heart Failure (HF) Hospitalizations in Para from 2017 to 2021 PEDRO ARTHUR RODRIGUES DE OLIVEIRA1, Pedro Arthur Rodrigues de Oliveira1, Marcello Vieira dos Santos1, Daniely Maues Beliqui1, Laura Coutinho Viana1, Jose Wilker Gomes de Castro Junior1, Jessica Lorena Alves2, Juliana Miranda Benicio3, Juliane Costa Santos3, Lucian Herlan da Costa Luz Fernandes3, Ligia Maria dos Santos de Oliveira Vieira1, Amanda Caricio Gomes1 (1) Centro Universitario do Estado do Para (CESUPA); (2) Universidade Federal do Para; (3) Centro Universitario Metropolitano da Amazonia (UNIFAMAZ) Introduction: Heart failure (HF) is a syndrome characterized by the inability of the heart to maintain sufficient cardiac output for the body's metabolic needs, leading to ventricular dysfunction. In the pediatric population the most common cause of HF is congenital anomalies, such as cardiac malformation. Other less frequent causes are myocardiopathies, myocarditis, and arrhythmias. Objectives: For this reason, this paper aims to conduct an evaluation of the epidemiological profile of hospitalizations for heart failure iciency in Para (Brazil) in the period from 2017 to 2021 in pediatric patients. Methodology: A descriptive, retrospective, quantitative study was conducted based on secondary data provided by the Hospital Information System (SIH) of the SUS Computer Department (DATASUS). The collected information was stored and tabulated in the Microsoft Office ExcelTM program. Results: Among the 1,577 cases found after analyzing the evaluated period, there are the years 2017 with 327 cases (20.73%), 2018 with 379 cases (24.03%), and 2019 with 311 notified cases (19.72%), being the 3 most incident years of the investigated period. The municipalities with the highest number of hospitalizations for heart failure were: Belem (79.64%) followed by Breves (1.83%) and Santarem and Altamira (1.5% each). Moreover, it was identified that mixed race, with 1,130 cases (71.65%), female gender, with 798 cases (50.60%) and the age group of less than 1 year, with 578 cases (36.65%) are the most affected epidemiological variables. After evaluating the cases reported, it was noted that 104 cases (6.59%) died. Conclusion: It was observed, therefore, that patients under the age of 1 year had a higher prevalence of hospitalizations for heart failure, which may be associated with hypertrophic congenital heart diseases. Moreover, the considerable amount of deaths is evident, reflecting the need for attention to pediatric HF. 110500 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Inflammatory Markers and Refractory Hypertension CARLOS FILIPE DOS SANTOS PIMENTA1, Taissa Lorena dos Santos1, Camila Bello Nemer1, Gabriela da Silva Nascimento1, Hugo Farah Affonso Alves1, Lucca Hiroshi de Sa Kimura1, Bernardo Chedier1, Arthur Fernandes Cortez1, Elizabeth Silaid Muxfeldt1 (1) Universidade Federal do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho Introduction: Refractory hypertension (RfHT) is defined as an uncontrolled blood pressure (BP) despite the use of 5 or more antihypertensives, including spironolactone and it is considered an extreme phenotype of resistant hypertension (RHT). High BP levels lead to RAAS stimulation, sympathetic hyperactivity and endothelial dysfunction with consequent production of pro-inflammatory cytokines. Objective: To evaluate the relationship between inflammatory markers and refractory hypertension in a large cohort of patients with RHT. Methods: A cross-sectional study that evaluated 423 resistant hypertensives (30.5% male, mean age 63.9 +- 10.8 years), of which 62 (14.6%) diagnosed as RfHT. All of them were submitted to the dosage of inflammatory markers: TNF-alpha, MCP-1, E-selectin and PAI-1. Socio-demographic and anthropometric characteristics and cardiovascular risk factors (CV) were recorded. Variance analysis compared serum levels of the 4 inflammatory markers and bivariate analysis compared patients with RHT versus RfHT. Results: Patients with RfHT are younger, with higher prevalence of smoking, higher levels of albuminuria and higher prevalence of chronic cerebrovascular and renal disease stages 4 and 5. PAI-1 values (126 [108-162] vs 118 [94-153] were higher in those with RfHT, although they did not reach statistical significance. The other biomarkers evaluated showed no association with the diagnosis of RfHT. Conclusion: Among inflammatory markers, PAI-1 was the one that correlated most strongly with refractory hypertension. Our study is the first one to demonstrate PAI-1 association with treatment refractoriness. 110881 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Cardiovascular Events Associated with White Coat Hypertension ALAYN KLEBER FREIRE DA SILVA JUNIOR1, Adelyanne Santos Barbosa1, Alayn Kleber Freire da Silva Junior1, Barbara Maria Oliveira da Silva1, Guilherme de Azevedo Guedes1, Marco Antonio Mota Gomes2 (1) Centro Universitario CESMAC, Maceio, AL, Brazil; (2) Centro de Pesquisas Clinicas Dr. Marco Mota, Maceio, AL, Brazil Introduction: Systemic Arterial Hypertension is a chronic disease with a multifactorial condition characterized by blood pressure (BP) levels above or equal to 130 and/or 80 mmHg. The combination of BP measurements in the office and Home Blood Pressure Monitoring (HPBM) and Ambulatory Blood Pressure Monitoring (ABPM) made it possible to define BP standards, including White Coat Hypertension (WCH). HAB is characterized by the elevation of BP in the office during repeated visits, concomitantly with normal values of BP out of the office, verified through ABPM and HMBP. Objective: This study aims to identify and analyze evidence about cardiovascular events associated with White Coat Syndrome. Methodology: A literature search was performed using the descriptors: White Coat Hypertension, Cardiovascular and Events together with the Boolean operator "AND" in MedLine/PubMed, Lilacs and Scielo databases. The use of these descriptors allowed the retrieval and restriction of articles. The filter of the last 5 years was used. The inclusion criterion used was the presence of keywords in the title or abstract of the articles. The following were excluded: letter to the editor, dissertations and theses. Reading steps: titles, abstracts, case reports and full articles. Results: Six articles were selected, and it was possible to observe that in a significant part of them, patients with WCH, in general, presented a higher level of cardiovascular alterations when compared to the group of normotensive individuals. Although these alterations were smaller when compared to individuals with sustained hypertension, individuals who suffer from WCH may manifest several anomalies, such as increased LV mass, thickness of the interventricular septum, structural alterations in the carotid artery and greater LA diameter. Because of these changes, WCH has been associated with negative physiological changes, such as sympathetic hyperactivity, which is related to increased cardiovascular risks. Considering this, some studies proposed to analyze the effectiveness of treatments with antihypertensive drugs, but in most of these, there was no reduction in cardiovascular events. Conclusion: In view of the aforementioned arguments, it can be inferred that the cardiac and vascular damages of patients diagnosed with WCH are greater when compared to normotensives, and further studies are needed to develop effective ways to reduce the problems brought about by WCH. 110591 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Impact of Preoperative Pulmonary Hypertension on Early Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease GUSTAVO PINHEIRO SANTANA1, Gustavo Pinheiro Santana1, Rodrigo Morel Vieira de Melo2, Taina Teixeira Viana1, Ana Luisa de Aguiar Almeida Silva2, Joao Pedro Martins Moreira Granja2, Osvaldemar Regis Do Nascimento Junior1, Danilo Sousa Sampaio1, Thais Harada Campos1, Edmundo Jose Nassri Camara1, Luiz Carlos Santana Passos1 (1) Hospital Ana Nery, Salvador - Ba (HAN); (2) Universidade Federal da Bahia (UFBA) Introduction: Rheumatic valve disease is still a health problem worldwide. Pulmonary hypertension (PH) may occur with the gradual progression of mitral stenosis and regurgitation in this condition. Whether or not PH is associated with early surgical mortality in this specific population remais controversial. Objective: In a population of patients undergoing cardiac surgery for rheumatic mitral valve disease, evaluate the impact of preoperative PH on early surgical mortality. Methods: This is a retrospective cohort carried out from January 1, 2017 to December 30, 2020. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with functional tricuspid regurgitation in an echocardiogram performed up to 6 months before surgery were included. Systolic pulmonary artery pressure (sPAP) value was also defined by preoperative echocardiogram evaluation. The primary outcome was surgical mortality. Results: 144 patients were included. The mean age was 46.2 (+-12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67) and sPAP was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The predominant valve disease was mitral stenosis (74.3%). The prevalence of severe tricuspid regurgitation was 47.2%. The total in-hospital mortality was 15 (10.4%) individuals. sPAP was independently associated with early surgical death RR 1.04 (1.01-1.07), p = 0.003. To determine a sPAP cut-off that indicates higher mortality and help decision making in clinical practice, we performed an analysis through the ROC curve (area 0.70, p = 0.012). The estimated value of 73.5 mmHg has the highest accuracy in our model for predicting early mortality. Conclusion: In patients with rheumatic heart disease who will undergo mitral valve surgery, pulmonary hypertension is associated with higher early mortality. Values above 73.5 mmHg predict higher risk and, in this part of the population, additional measures to control intraoperative and immediate postoperative pulmonary hypertension should be considered. 110617 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Association between Phase Angle and Coronary Artery Calcium Score in Patients on Peritoneal Dialysis FABRICIO MOREIRA REIS1, Maryanne Zilli Canedo Silva1, Nayrana Soares Carmo Reis1, Fabiana Lourenco Costa1, Caroline Ferreira da Silva Mazeto Pupo da Silveira1, Alejandra Del Carmen Villanueva Mauricio1, Joao Carlos Hueb1, Rodrigo Bazan1, Pasqual Barretti1, Luis Cuadrado Martin1, Silmeia Garcia Zanati Bazan1 (1) Faculdade de Medicina de Botucatu - Universidade Estadual Paulista Introduction: The phase angle has been used as a nutritional marker and predictor of mortality in patients on peritoneal dialysis. The coronary artery calcium score has showed to predict the incidence of acute myocardial infarction and death from cardiovascular disease in these patients. However, the association between phase angle and coronary artery calcium score in patients on peritoneal dialysis is not well established. Objective: To evaluate the association between phase angle and coronary calcium score in patients on peritoneal dialysis. Methods: This was a cross-sectional study with patients on peritoneal dialysis, followed up at a University Hospital, between March 2018 and August 2019. Phase angle was evaluated by unifrequency bioimpedance. The coronary artery calcium score was calculated based on cardiovascular computed tomography, considering positive when greater than or equal to 100 Agatston and negative when less than 100 Agatston. Results: We evaluated 44 patients on dialysis, with mean age of 56 years and 11.7 months. In a univariate analysis, an association was observed between the coronary artery calcium score, the presence of atherosclerotic plaque in the carotid artery, and the difference in systolic blood pressure in the upper extremities with the phase angle. In the hierarchical multivariate logistic regression, only the coronary artery calcium score maintained an association with the phase angle in the final model. Conclusion: The phase angle is associated with a positive coronary artery calcium score in patients on peritoneal dialysis, and despite other factors, may be useful as a risk marker for coronary artery disease in this population. 110620 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING The Left Atrium as a Predictor of Coronary Calcification in Patients on Peritoneal Dialysis FABRICIO MOREIRA REIS 1, Maryanne Zilli Canedo Silva1, Nayrana Soares Carmo Reis1, Fabiana Lourenco Costa1, Caroline Ferreira da Silva Mazeto Pupo da Silveira1, Alejandra Del Carmen Villanueva Mauricio1, Joao Carlos Hueb1, Rodrigo Bazan1, Pasqual Barretti1, Luis Cuadrado Martin1, Silmeia Garcia Zanati Bazan1 (1) Faculdade de Medicina de Botucatu - Universidade Estadual Paulista Introduction: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD). The assessment of coronary calcification by coronary artery calcium (CAC) score has shown to predict the incidence of acute myocardial infarction and death by CVD in those patients. Left atrial volume has also been associated with acute myocardial infarction and cardiovascular events. Objective: To assess the association between left atrial volume and CAC score in PD patients. Methods: A cross-sectional study with PD patients, followed up between March 2018 and August 2019, including demographic, clinical and laboratory data collection; assessment of nutritional status by anthropometry and bioimpedance; protocol of residual renal function and adequacy of dialysis (Kt/V); doppler echocardiogram, carotid ultrasound, pulse wave velocity, ankle-brachial index and CAC. Patients were divided into two groups: positive or negative CAC score. Comparisons between groups were performed using the Chi-square, Student t or Mann-Whitney test (p < 0.05). Results: 44 patients on PDP, mean age of 56 years. Main cause of CKD was hypertension. Median time on dialysis therapy was 11.7 months. In the univariate analysis, a significant association of CAC score was observed with variables such as age, diabetes mellitus, over hydration, femoral pulse wave velocity, left atrial volume index, E/A ratio and left ventricular mass index, but in the multivariate analysis, only the left atrial volume index was related to a positive CAC score, odds ratio of 1.71. Conclusion: The left atrial volume index is associated with positive CAC score in patients with CKD undergoing PD, and it can be used as a risk marker for coronary artery disease in this population. 110669 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Dietary Indicators of Carbohydrate Quality and Blood Pressure in Brazilian Adolescents VANESSA PROEZA MACIEL GAMA1, Camilla Medeiros Macedo da Rocha4, Edna Massae Yokoo6, Amanda de Moura Souza7, Katia Vergetti Bloch7, Rosely Sichieri5 (1) Instituto Federal de Educacao, Ciencia e Tecnologia Fluminense - IFFlumnense, Av. Souza Mota, 350, Parque Fundao, CEP 28060-010, Campos dos Goytacazes, RJ, Brazil;; (2) Instituto de Saude Coletiva, Universidade Federal Fluminense - UFF, Rua Marques de Parana, 303, 3deg andar, Centro, CEP 24030-210 Niteroi, RJ, Brazil;; (3) Curso de Especializacao em Nutricao Clinica, Instituto de Nutricao Josue de Castro, Universidade Federal do Rio de Janeiro - UFRJ, Av. Carlos Chagas Filho, 373 - bloco J 2deg andar, Ilha do Fundao, CEP 21941-902, Rio de Janeiro - RJ, Brasil.; (4) Instituto de Alimentacao e Nutricao, Centro Mutidisciplinar - UFRJ - Macae, Universidade Federal do Rio de Janeiro, Av. Aluizio da Silva Gomes, 50, Novo Cavaleiros, CEP 27930-560 Macae, RJ, Brazil;; (5) Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro - UERJ, Rua Sao Francisco Xavier, 524, Pavilhao Joao Lyra Filho, 7deg andar, CEP 20550-900 Rio de Janeiro, RJ, Brazil;; (6) Departamento de Epidemiologia e Bioestatistica, Universidade Federal Fluminense - UFF, Rua Marques de Parana, 303, 3deg andar, Centro, CEP 24030-210 Niteroi, RJ, Brazil;; (7) Instituto de Estudos em Saude Coletiva, Universidade Federal do Rio de Janeiro -UFRJ, Avenida Horacio Macedo, s/n, Ilha do Fundao, CEP 21941-598, Rio de Janeiro, RJ, Brazil; Introduction: The consumption of foods and meals with high glycemic index (GI) and high glycemic load (GL) have been suggested as risk factors for chronic diseases, including hypertension. Population-based studies that have investigated this association in adolescence are still scarce. Objective: To evaluate the association between dietary indicators of glycemic response and changes in blood pressure among adolescents in the Study of Cardiovascular Risk in Adolescents (ERICA). Methods: A sample (n = 69,057) of students (12 to 17 years) from public and private schools, representative of Brazilian adolescents living in cities with 100,000 inhabitants or more was evaluated. Prevalence of hypertension was estimated, as well as mean systolic and diastolic blood pressures (mmHg) stratified by sex and age group and mean dietary indicators of glycemic response: daily GI, average GI, GI of the first meal of the day, daily GL, average GL and GL of the first meal of the day, according to sex and age group. Linear and logistic regression models stratified by sex and adjusted for age and body mass index were estimated to assess association between dietary indicators of glycemic response and systolic, diastolic blood pressures and hypertension. Results: The mean age was14.7 years and 56% female. The prevalence of hypertension was 9.1%, almost twice more frequent among boys (12.3%), compared to girls (6.5%). The mean systolic blood pressure was 110.6 mmHg and the mean diastolic blood pressure was 65.8 mmHg. Boys had higher mean dietary indicators of glycemic response (GI of first meal, daily GL, average GL, and GL of first meal) compared to girls (p-value < 0.05), except for mean GI and mean GL. There was a positive association between GI of the first meal with systolic blood pressure in boys. Conclusions: Factors related to carbohydrate metabolism and the nutritional value of the diet should include GI and GL of individual meals, beyond the global indicators of glycemic response such as daily GI and GL. Further studies are needed to deepen the relationship between the glycemic response from food intake. 110759 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Assessment of Cardiac Adverse Events Following COVID-19 Vaccination by Tissue Speckle Tracking SRISAKUL CHAICHUUM1, Shuo-Ju Chiang2, Masao Daimon3, Su-Chen Chang2, Chih-Lin Chan2, Chu-Ying Hsu2, Ching-Li Tseng1 (1) Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan; (2) Division of Cardiology, Department of Internal Medicine, Taipei City Hospital Yangming Branch, Taipei, Taiwan; (3) Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan Background: Cardiac discomfort has been reported periodically in individuals who received COVID-19 vaccines. Transient cardiac symptoms are imperatively monitored to evaluate changes in heart function. Objective: This study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Methods: In total, 121 subjects who received at least one dose of a COVID-19 vaccine within 6 weeks were recruited. Serological markers and echocardiography were assessed. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. Results: After vaccination, 66 individuals (55.4 +- 17.4 years) developed cardiac discomfort, such as chest tightness (n = 59, 89%), palpitations (n = 23, 35%), dyspnea (n = 21, 32%), and chest pain (n = 6, 9%). All had normal serum levels of creatine phosphokinase (93.0 U/L; IQR, 66.5-137.5), creatine kinase myocardial band (10.4 U/L; IQR, 2.3-14.7), Troponin T (6.0 ng/L; IQR, 4.0-8.5), N-terminal pro b-type natriuretic peptide (44.5 pg/mL; IQR, 20.2-79.5), platelets (222.0 x 103/mL; IQR, 199.2-275.5), and D-dimer (0.3 mg/L; IQR, 0.1-0.4). Echocardiogram presented left ventricular ejection fraction in the symptomatic group (71.41% +- 7.12%) and the control group (72.18% +- 5.11%) (p = 0.492) were normal. However, the symptomatic group had a greater ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e') than the normal group (9.32 +- 3.56 vs 7.74 +- 2.34, respectively; p = 0.005), correlated with e' (8.64 +- 3.96 vs 10.25 +- 3.58, respectively; p = 0.023). Use of 2D-STE showed that global longitudinal strain (GLS) and global circumferential strain (GCS) were reduced in the symptomatic group (17.86% +- 3.22% and 18.37% +- 5.22%) compared to the control group (19.54% +- 2.18% and 20.73% +- 4.09%) (p = 0.001 and p = 0.028). Conclusions: COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable evaluation of the subtle changes in myocardial function after vaccination. 110780 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION Cost-Effectiveness of Rivaroxaban Versus Warfarin in New Onset Atrial Fibrilattion After Coronary Artery Bypass Graft Surgery (Task POAF): A Prospective, Single Center and Randomized Trial MARCEL DE PAULA PEREIRA1, Eduardo Gomes Lima1, Fabio Grunspun Pitta1, Luis Henrique Wolff Gowdak1, Bruno Mahler Mioto1, Luiz Antonio Machado Cesar1, Henrique Trombini Pinesi1, Omar Asdrubal Vilca Mejia1, Fabio Biscegli Jatene1, Roberto Kalil Filho1, Francisco Carlos da Costa Darrieux1, Carlos Vicente Serrano Junior1 (1) Instituto do coracao - Universidade de Sao Paulo Introduction: New post-operative atrial fibrillation (POAF) in the setting of coronary artery bypass graft (CABG) is an entity observed in up to 40% of procedures. Despite this, there is little evidence about the use of direct oral anticoagulants in this scenario. Purpose: Our aim was to compare cost-effectiveness of a strategy using rivaroxaban versus the standard therapy after POAF. Methods: This is a single center, randomized, prospective and open-label study comparing two anticoagulation strategies: Warfarin associated with bridging with enoxaparin versus rivaroxaban after POAF. Medications started during hospitalization and continued up to 30 days. Primary endpoint was the assessment of cost-effectiveness. Costs were analyzed from the perspective of supplementary health in Brazil and converted to US dollars. Quality-adjusted life year (QALY) were assessed using the SF-6D questionnaire. Safety endpoint was any bleeding using the international society of thrombosis and haemostasis. Results: In a tertiary hospital, 51 patients who underwent CABG and presented with POAF were randomized. Twenty-six patients were randomized for the warfarin group and 25 for the rivaroxaban group. Both groups had similar baseline. The median of the primary cost-effectiveness outcome was $ 1347,7 in the warfarin group and $433,0 in the rivaroxaban group (p < 0.001), as shown in Figure 1. The result of the SF-6D questionnaire showed no statistical difference between groups. Bleeding rates were 26% in warfarin and 12% in rivaroxaban group (p = 0.18). Conclusion: In this study with a 30-day follow-up, anticoagulation strategy with rivaroxaban in patients with POAF was more cost-effective the standard therapy using warfarin. 110933 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION The use of Anticoagulant for Preventing the Formation of Thrombosis in Patients who Have Undergone Plastic Surgery: A Systematic Review MARCELLO VIEIRA DOS SANTOS1, Cassiane da Silva Portela Pinto2, Jessica Lorena Alves3, Pedro Arthur Rodrigues de Oliveira1, Izadora Avelar Neto2, Daniely Maues Beliqui1, Roberta Louise dias Rodrigues1, Adilson talis Ferreira dos Santos1 (1) Centro Universitario do Estado do Para; (2) Universidade do Estado do Para; (3) Universidade Federal do Para Introduction: Thrombosis is formed from clots in the circulatory system, and is related to venous stasis, trauma, surgery, and others, and can evolve to more fatal conditions, such as pulmonary thromboembolism. To avoid this condition, it is necessary to start anticoagulant therapy early. This condition is recurrent in the postoperative period of plastic surgery, being aggravated by the non-use of elastic stockings, the stimulation of early ambulation, the use of anticoagulants, and the failure of risk analysis. Therefore, this paper discusses anticoagulants in the postoperative period of plastic surgery as a way to prevent thrombosis. Objectives: To analyze the use of anticoagulants as a prophylactic form for thrombosis formation in the postoperative period of patients undergoing plastic surgery. Methods: This is a systematic review of literature, based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyse - PRISMA. We used the term "(anticoagulants) AND (thrombosis) AND (disease prevention)" in the LILACS, PubMed and Scielo databases, obtaining initially 65 publications and after the PRIMAS guidelines, 7 remained for analysis. Results And Discussions: Throughout the studies, it was seen the presence of Virchow's triad in the postoperative period of plastic surgery, characterized by venous stasis, endothelial injury and hypercoagulation. For this, it was observed, only the Caprini score as recommended for risk assessment in the postoperative period. Regarding anticoagulants, it was shown vitamin K antagonists, Factor Xa inhibitors (heparins), direct oral Factor Xa inhibitors (rivoraxaban) being the first line of choice, however there are still many discussions about the ideal propedeutics, leading to its irrational use, since its excess can bring bleeding and smaller doses do little effect. Conclusion: Thus, the diversification of methods for the evaluation of venous thromboembolism (VTE) were shown to be necessary in plastic surgery, since only one method of choice was analyzed, which ends up hindering the patient's risk assessment. Similarly, the creation of a protocol by the Brazilian Society of Plastic Surgery, addressing VTE in the postoperative period could standardize chemoprophylaxis and make it more effective. Finally, greater follow-up of patients at higher risk by a hematologist also shows promise for improving the efficacy of therapy. 110782 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY The Overestimation of the Prevalence of Mismatched Aortic Prosthesis After Transcatheter Implantation by Echocardiography FERNANDO COUTO PORTELA1, Sayuri de Souza Yamamura1, Francisco Expedito de Albuquerque Filho1, Marcus Vinicius Alves Gomes1, Luis Felipe Mousinho Lima de Carvalho1, Marco Tulio Hercos Juliano1, Marcio Mesquita Barbosa1, Ana Claudia Conrado de Oliveira1, Gustavo Travassos Gama1, Marcio Mendes Pereira1 (1) UDI Hospital Introduction: The valve prosthesis-patient mismatch (PPM) is characterized by a small effective orifice area (AOE) in relation to the body surface, resulting in high transvalvular gradients. The presence of MPP in the scenario of transcatheter aortic valve implantation (TAVI) has different characteristics according to the type of prosthesis (balloon-expandable or self-expanding). Knowing the real prevalence of PPM in a real-world sample is very important since such presence impacts survival, functional recovery, hospitalization for heart failure and valve durability. Objectives: To determine the prevalence of PPM in a sample of patients undergoing TAVI, using predicted AOE and AOE measured by the continuity equation. Associate the presence of PPM with several clinical, echocardiographic, tomographic variables and with the type of prosthesis used. Method: An observational study was performed with 26 consecutive patients undergoing TAVI in a private hospital. PPM was defined as present if AOE <0.85 cm2/m2 (<0.70 cm2/m2 if obese). The predicted PPM was obtained from data provided in the medical literature according to the size and prosthesis used. Results: All 26 patients who underwent TAVI within the 9-year period were included in the study. The mean age was 78.9 +- 8.3 years and 57.7% were male. The measured prevalence of PPM was considerably higher (41.7%) than predicted (15.4%). The mean residual gradient was 18.7 +- 4.4 mmHg in patients with PPM and 10.5 +- 4.5 mmHg in patients without PPM (p = 0.029). The rate of PPM in balloon-expandable prostheses was significantly higher than in self-expanding prostheses (42.9% vs. 5.3%, p = 0.018). Patients with PPM had a smaller area of the aortic annulus measured by tomography than those without PPM (3.34 +- 0.16 cm2 vs. 5.06 +- 1.95 cm2, p = 0.014). Conclusion: The use of the AOE calculated by the continuity equation overestimated the prevalence of PPM in patients undergoing TAVI. PPM was more prevalent in balloon-expandable prostheses than in self-expanding ones. Reduced aortic annulus was another factor associated with PPM. 111196 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Modified CHA2DS2VASC Score as Prognostic Risk of Developing Severe COVID-19 YURI CAVALCANTI ALBUQUERQUE TENORIO1, Priscila Alves da Silva2, Ana Livia de Oliveira Barros2, Gabriel Noe Albuquerque Paffer Cruz2, Nicole de Lima Larre Barbosa4, Carolline Cavalcante de Melo3, Ana Clara Valente de Lima Melo3, Arthur Henrique Fernandes Rodrigues2, Edecio Galindo de Albuquerque1, Antonio Everaldo Vitoriano de Araujo Filho2, Francisco de Assis Costa2 (1) Hospital Veredas; (2) Centro Univesitario Tiradentes; (3) Universidade Federal de Alagoas; (4) Universidade Estadual de Ciencias da Saude de Alagoas Introduction: Covid-19 was declared a pandemic in early 2020 by the World Health Organizations (WHO) and it is a respiratory disease caused by SARS-CoV-2 virus. One of its main complications is the development of coagulopathies, given that the infection promotes increased thrombin formation and hypercoagulability state. The modified CHA2DS2-VASc score is used to estimate the risk of thromboembolic stroke in atrial fibrillation, as well as the thrombotic risk in other heart diseases. The abbreviation stands for congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack. The risk factors that make up the m-CHA2DS2VASc score could also be recognized as risk factors for mortality in patients with COVID-19. The aim of this study is to identify the association between m-CHA2DS2VASc score in mortality and hospital staying in Covid-19 patients to use it as prognostic score of severe disease. Methods: Case-control study in a philanthropic hospital in the Brazilian state of Alagoas, selecting 103 hospitalized patients from 2020 to 2021 aged more than 18 years old and diagnosed with SARS- infection. The statistical analysis was calculated using Fisher's Exact test. Results: The mean m-CHA2DS2VASc score. was 1,74 (SD 1,53) and mean age was 53.81 years (SD 17.37). There was a significant relationship between CHA2DS2VASc score and mortality rate (p = .003) and hospital staying (p = .009). Discussion: The results lead us to associate m-CHA2DS2VASC score to risk of death (any cause). Another similar study with 864 patients also found this relation with m-CHA2DS2VASc score and death (p < .001). Other authors suggest that m-CHA2DS2-VASc score can be used to discern patients with higher thromboembolic risk. Also, higher m-CHA2DS2-VASc score is associated with a higher need for mechanical ventilation and a greater risk of death. Conclusion: There was a relationship between m-CHA2DS2VASc score and development of severe covid-19 and mortality according to the population analysed and other similar studies. 110794 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Epigallocatechin-3-Gallate (EGCG) Supplementation in Heart Failure: Systematic Review of Animal Experiments YURI CAVALCANTI ALBUQUERQUE TENORIO1, Thayrone Romario da Silva Santos1, Francisco de Assis Costa2 (1) Hospital Veredas; (2) Universidade Federal de Alagoas Introduction: Epigallocatechin-3-gallate (EGCG) is a natural flavonoid present in green tea leaves with important therapeutical effects such as antioxidant properties, reduction of free radicals involved in numerous chronic diseases. The literature identifies a strong correlation between EGCG supplementation and the treatment and prevention of cardiovascular diseases; consequently, this flavonoid is a potential adjuvant for patients with several clinical conditions, such as arterial hypertension, cardiac heart failure (CHF), arrhythmias, chronic coronary disease, or acute myocardial infarction. Therefore, this paper aims to identify correlation between EGCG extracted from green tea leaves and treatment of CHF. Methods: A systematic literature review was developed selecting seven original articles, focusing on laboratory experiments in animal models. Results and discussion: The results found that EGCG supplementation promoted treatment of CHF and cardiac remodelling prevention from reducing heart weight (lower p was < .0001), increasing left ventricle ejection fraction (lower p was < .01), decreasing protein expression levels of hypertrophy markers, such as brain natriuretic peptide (BNP) in animal models (lower p was < .01), and reducing mortality in one study (p < .05). Conclusion: Therefore, it was possible to conclude that there is a positive relationship between EGCG supplementation with the treatment and prevention of CHF. However, although laboratory tests in animal models have positive results, multicentered randomized clinical trials in the population are necessary to define the actual association of this substance in humans. 110809 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY Cardio-Oncology on Demand: Applying a Protocol to Classify and Identify Patients to be Referred to a Cardio-Oncologist GISELE PLACA RODRIGUES OLSON1, Eduardo Schlabendorff1, Euler Manenti1, Jairo Lewgoy1 (1) Hospital Mae de Deus, Porto Alegre/RS - Brasil Summary Base: Cardiovascular diseases (CVD) and cancer (CA) are the main causes of death in Brazil. Its incidences are associated with rising in life expectancy and various common risk factors. With the improvement of CA treatment and the increasing number of survivors, the event of CVD in these individuals has also been increasing, due to the impacts of the anticancer drugs in the cardiovascular (CV) system, which is called cardiotoxicity. Cardio-oncology becomes essential for early identification, treatment, and prevention of such complications. Our practice suggested a protocol capable of stratifying cancer patients according to the risk of cardiotoxicity. Purpose: The purpose of this study was to estimate the number of patients that were at elevated risk for cardiotoxicity, at their first oncology visit. And the amount of them were referred for an evaluation in cardio-oncology. Methods: We reviewed 104 medical records of patients who had their first appointment at the oncology department of Hospital Mae de Deus, in Porto Alegre/RS, from June 1 to August 31, 2019. To stratify them, we filled out an appropriated protocol based on guidelines. Results: We have identified that 87 (83%) patients at elevated risk for cardiotoxicity, which should be evaluated by a cardio-oncologist. Only 15 (17.2%) were referred. The risk determinants are in the figure. Conclusion: We have shown that most patients seen at the first visit to an oncologist had a substantial risk of cardiotoxicity, but only few were actually referred to the cardio-oncologist department. This initiative encourages initial cardiologic evaluation routine in patients who will undergo therapies with potential cardiotoxicity. 110812 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Long-Term Outcomes of PCI vs CABG in Diabetic Patients with Left Main Coronary Disease: A Meta-Analysis of Randomized Controlled Trial PEDRO EMANUEL DE PAULA CARVALHO1, Thiago Mamede Alencastro Veiga1, Gabriel Venturim Porto1, Felipe Sarsur de Lanna Machado1 (1) School of Medicine, Federal University of Minas Gerais Introduction: It has been recognized that diabetic patients with complex coronary artery disease have poor outcomes when undergoing Percutaneous Coronary Intervention (PCI) compared to Coronary Artery Bypass Grafting (CABG). However, among diabetic patients with unprotected Left Main Coronary Artery (LMCA) disease, the optimal method is not established. Objectives: Evaluate long-term outcomes after PCI with drug-eluting stents, as compared with CABG in diabetic patients with unprotected Left Main Coronary Artery (LMCA) disease. Methods: MEDLINE, ClinicalTrials, and Cochrane databases were searched for randomized clinical trials (RCTs) that reported outcomes after PCI with drug-eluting stents vs CABG in unprotected LMCA disease among the diabetic population. We chose a minimum follow-up period of 3 years. Trial level Risk Ratios (RRs) and 95% confidence intervals (CIs) were pooled by random-effects modeling. The risk of bias was estimated by assessing funnel plots. PRISMA-IPD guideline was followed to present the data. Results: Four RCTs including 1080 patients were identified, of whom 553 (51.2%) underwent PCI. The risk of composite endpoints of death, myocardial infaction, stroke or revascularization was higher after PCI compared with CABG (RR 1.30, 95% CI [1.09-1.56], P = 0.0037, I2 = 0%). There was no difference for individual endpoints of deaths, cardiovascular death and myocardial infarction (RR 1.32, 95% CI [0.94-1.85], P = 0.1131, I2 = 0%; RR 1.29, 95% CI [0.76-2.18], P = 0.3405, I2 = 0%; RR 0.94, 95% CI [0.61-1.45], P = 0.7881, I2 = 0%, respectively), however the risk of stroke was higher in CABG group (RR 0.41, 95% CI [0.18-0.94], P = 0.0351, I2 = 0%) meanwhile the risk of any revascularization was higher in PCI group (RR 1.99, 95% CI [1.44-2.75], P < 0.0001, I2 = 0%). There was no difference between groups with respect to graft occlusion or stent thrombosis (RR 0.66, 95% CI [0.19-2.31], p = 0.5162, I2 = 64,6%). Conclusion: A higher risk of revascularization was associated with PCI compared to CABG in diabetic patients with left main coronary disease. This finding affects the composite endpoint that favors CABG. However, the risk of stroke was greater in patients submitted to CABG and no significant difference was found between the other outcomes evaluated (MI, cardiovascular death, and total deaths) when analyzed individually. These findings could help with the decision-making between PCI and CABG in diabetic patients with unprotected LMCA disease. 110830 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Clinical-Angiographic Profile and Procedural Outcomes in Patients Undergoing Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery Disease: An Observational Study GUSTAVO PAES SILVANO1, Rodrigo Pinheiro Amantea1, Guilherme Pinheiro Machado1, Andre Luiz Theobald1, Alan Pagnoncelli1, Luiz Carlos Corsetti Bergoli1 (1) Hospital de Clinicas de Porto Alegre (HCPA) Introduction: Left main coronary intervention is increasingly used as a treatment option for unprotected left main coronary artery (ULMCA) lesions due to technical improvements in percutaneous coronary intervention (PCI), stent technology and new guideline recommendations. Objectives: To report the clinical profile, angiographic status, and procedural outcomes in patients undergoing ULMCA PCI. Methods: A prospective observational study including all consecutive patients with ULMCA who underwent PCI at a tertiary hospital in Southern Brazil between January 2017 and February 2022. Data including clinical-demographic profile, angiographic details and procedural complications were analyzed. Results: A total of 206 patients were investigated, of which 63.1% were male, with a mean age of 67.7 +- 11.4 years. Hypertension and diabetes were the most common risk factors, present in 81.1% and 44.2% of patients, respectively. Smoking, previous acute myocardial infarction, chronic kidney disease, heart failure and peripheral vascular disease were present in 43.9%, 22.3%, 22.3%, 15.5% and 11.7% patients respectively. Chronic stable angina was the most common mode of presentation (32.5%), followed by non-ST-segment elevation myocardial infarction (23.8%), ST-segment elevation myocardial infarction (16.5%) and unstable angina (15%). The percentage of patients with single-, double-, and triple-vessel coronary disease (in addition to left main stenosis) was 28.6%, 20.9%, and 39.3%, respectively. Isolated ULMCA lesion was present in 11.2% patients and left main bifurcation lesions in 70.9%. Majority of the procedures were performed via femoral approach (63.6%). The median stent number placed was 2 (1-3) and the median contrast volume used was 240 mL (175-300). Predilatation with balloon was performed in 90.8% of patients and postdilatation in 96.1%. Pre-PCI ultrasound was used in 31.2% of patients and 42.9% following stent implantation. Procedure related complications occurred in 19 (14.6%) cases. Most common among these were distal embolization (3.4%), side branch occlusion (3.4%), and no reflow phenomenon (2.4%). Procedure related mortality was 1.0% and occurred exclusively in acute coronary syndrome patients. Among the 18 patiens who died during hospitalization, 12 (66.7%) had cardiogenic shock at presentation. Conclusion: ULMCA PCI was safely performed and presented excellent results in this single-center prospective registry. 110843 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Three-Year Follow-Up of Chronic Coronary Syndrome Patients in a Specialized Center in Brazil HENRIQUE TROMBINI PINESI1, Eduardo Martelli Moreira1, Cibele Larrosa Garzillo1, Eduardo Bello Martins1, Fabio Grunspun Pitta1, Paula Martins Paulino Bolta1, Carlos Alexandre Wainrober Segre1, Desiderio Favarato1, Roberto Kalil Filho1, Fabiana Hanna Rached1, Eduardo Gomes Lima1, Carlos Vicente Serrano Junior1 (1) Instituto do Coracao, Faculdade de Medicina, Universidade de Sao Paulo Introduction: Incidence of cardiovascular events in patients with Chronic Coronary Syndrome (CCS) may vary significantly between geographical regions. Although populous, Brazil is often underrepresented in international registries. Objective: This study aimed to describe the quality of care and 3-years incidence of cardiovascular events and associated prognostic factors in CCS patients in a tertiary public health care center in Brazil. Methods: Patients with CCS (either previous revascularization, myocardial infarction, or stenosis >50% in at least one epicardial coronary artery) presenting for clinical evaluation were enrolled and followed for at least 3 years. The main endpoint was the composite of MI, stroke, or death. We also evaluated prescription, symptoms, and laboratory records. Results: 844 patients with mean age of 65 (+-9.4) years, 31.3% women, were included. Previous MI was present in 60.9%, previous CABG in 28.8%, and previous PCI in 44.5%. Diabetes was prevalent in 49.6% and high blood pressure in 86.7%. The use of aspirin was prevalent in 90.9% of the patients, 21.2% with dual antiplatelet therapy, and only 7.1% with no antiplatelet agent. Statins were prescribed to 94.4% of the patients, with high-intensity statin therapy in 68.2%. At a median follow-up (FU) of 881 days, we recorded 70 events of primary composite endpoint, with a 3-year estimate event incidence of 8.3%. Age (1.54, 95%CI 1.32-1.90), stroke (2.62, 95%CI 1.18-5.84), LDL (1.10, 95%CI 1.03-1.18) and left ventricular function (0.84, 95%CI 0.76-0.93) were the main prognostic factors in multivariate analysis. At admission, angina was present in 29.1% of the patients. This percentage dropped to 16.3 after follow-up. On the other hand, there was no improvement in the LDL levels. Conclusion: CCS patients at our institution had a 3-year incidence of the primary composite endpoint of 8.3%, the prescription of antiplatelet therapy and statins were high, and LDL-cholesterol was the main modifiable risk factor of worse prognosis. 110847 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Prognostic Value of Pulse Pressure in Heart Failure with Reduced Ejection Fraction DIANA SEIXAS FERRAO1, Joana Pereira1, Pedro Ribeirinho Soares1, Marta Soares Carreira1, Marta Amorim1, Catarina Elias1, Rita Gouveia1, Sergio Madureira1, Ana Neves1, Jorge Almeida1, Patricia Lourenco1 (1) Internal Medicine Department, Centro Hospitalar e Universitario de Sao Joao Introduction: Pulse pressure (PP) is the difference between systolic and diastolic blood pressure. Increased PP is a well-recognized cardiovascular risk factor but is less well established in HF, particularly with reduced ejection fraction (HFrEF). Objective: To study the prognostic role of increased PP in HfrEF. Methods: Retrospective cohort study of adult (>18 years) ambulatory patients with chronic HFrEF that were followed in a specialized HF clinic between January 2012 and May 2018. Patients with preserved ejection fraction and those with recovered ejection fraction were excluded. Patients with PP <=50 mmHg and PP >50 mmHg were compared. The 50 mmHg cut-off corresponded to the median value of PP distribution and to the midst of the normal range. Patients were followed-up to 5 years and all-cause mortality was the endpoint. A Cox-regression analysis was performed to study the association of PP with 5-year mortality. Interaction between PP and age (cut-off 80 years) was tested. The analysis was further stratified according to age strata: <80 years and >=80 years. Adjustments were made considering sex, hypertension, diabetes, atrial fibrillation, ischaemic aetiology, systolic dysfunction severity, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), renal function, B-type natriuretic peptide (BNP) and evidence-based therapy. Results: We studied 854 chronic HF patients. Mean age was 71 years and 65% were male. HF was ischaemic in 46.0% of the patients and 51.3% had severe systolic dysfunction. Median (Q1-Q4) PP was 51(40-64)mmHg. Patients with PP >50 mmHg were older, had higher SBP, less systolic disfunction and more often medicated with renin-angiotensin-aldosterone system inhibitors. During the 5-year follow-up, 391 (45.8%) patients died. Patients with PP >50 mmHg had no difference in death risk compared to those with lower PP: HR = 0.94 (95% CI: 0.77-1.15), p = 0.55. When the analysis was stratified according to age, in the subgroup of patients aged >=80 years, elevated PP was associated with survival benefit, HR of 0.58 (95% CI: 0.37-0.91), p = 0.02. No association with mortality existed in the group of patients <80 years. Conclusions: Elevated PP was not predictive of mortality in patients with chronic HF and in the subgroup of patients aged >=80 years, a PP >50 mmHg was associated with lower mortality, so it appears that age influences the impact of PP in mortality in HF. 110858 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Comparison between Cardiac and Non-Cardiac Patients Admitted to an Intensive Care Unit with COVID-19: Analysis of a Tertiary Center in Brazil HENRIQUE TROMBINI PINESI1, Eduardo Martelli Moreira1, Melina de Oliveira Valdo Giugni1, Pedro Henrique de Almeida Marins1, Eduardo Gomes Lima1, Fabio Grunspun Pitta1, Ludhmila Abrahao Hajjar1, Juliana Carvalho Ferreira2, Carlos Vicente Serrano Junior1, Cibele Larrosa Garzillo1 (1) Instituto do Coracao, Faculdade de Medicina, Universidade de Sao Paulo, Brazil; (2) EPICOV Study group, Faculdade de Medicina, Universidade de Sao Paulo, Brazil Background: Studies have shown an association between cardiovascular diseases and higher rates of mortality and complications in patients with COVID-19. The aim of this study was to compare mortality and other events in critically ill cardiac and non-cardiac patients with COVID-19 in a referral center intensive care unit (ICU) in Brazil. Methods: We analyzed data from a prospective registry of patients admitted to a tertiary hospital ICU for COVID-19 between March and June 2020. 1501 patients were admitted and 221 had heart disease. Continuous variables were described as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute frequency and percentage. To compare clinical and demographic characteristics, as well as laboratory tests between patients with and without heart disease, the Student's T test and the Mann-Whitney U method were used. For the occurrence of events, Fisher's exact test was used. Results: Patients with heart disease were older, and had a higher prevalence of diabetes and chronic kidney disease, compared to non-cardiac patients. On the other hand, the prevalence of cancer and obesity was higher among non-cardiac patients. Blood pressure, heart rate and oxygen saturation were similar between the groups, as well as the need of oxygen and ventilatory support. Patients with heart disease were more frequently using vasoactive drugs on admission. Patients with heart disease had worse renal function and higher cardiovascular biomarkers (troponin, NT-proBNP and D-dimer). Non-cardiac patients had higher values of CRP, leukocytes, lymphocytes and platelets. Surprisingly, in-hospital and ICU mortality were similar in both populations studied. Non-cardiac patients required more frequent orotracheal intubation and had more thrombotic events. In contrast, patients with heart disease had a higher occurrence of atrial fibrillation. Conclusion: In our center, the presence of cardiovascular disease in critically ill patients with COVID-19 was not associated with mortality compared with non-cardiac patients. 110863 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Implantation of a Cardioverter-Defibrillator Associated with Multisite Pacing in Patients with Persistent Left Superior Vena Cava ALFREDO AURELIO MARINHO ROSA FILHO3, Lucas Brandao Cavalcante2, Jose Carlos de Souza Neto2, Sara Carolline Gomes de Araujo Lima2, Alice Wanderley Rosa2, Dario de Moura1, Virginia Barreto1, Marcelo Russo1, Fabian Fernandes1, Flavio Loureiro1, Alfredo Aurelio Marinho Rosa1, Edvaldo Ferreira Xavier Junior1 (1) Santa Casa de Misericordia de Maceio - SCMM, AL; (2) Centro Universitario Tiradentes - UNIT, AL; (3) Hospital Universitario Professor Alberto Antunes - HUPAA/UFAL Background: Persistent left superior vena cava (PLSVC) is a rare venous anomaly, however, in the thorax it is the most frequent venous alteration with a prevalence of 0.3 to 0.5% in the general population. The PLSVC is asymptomatic and in most cases is identified during implantation of the cardiac device. Objective: To present the technique used to implant a cardioverter-defibrillator (ICD) with biventricular pacing (BIV) in patients with PLSVC. Material and Methods: Between March 2007 and April 2022, 776 multi-site cardioverter-defibrillators (ICD-CRT) were implanted, of which 4 patients (0.5%) had SEPVC. All patients had symptomatic HF and refractory to optimized drug treatment with recurrent hospitalizations for HF. The 4 patients were male. They presented LBBB on ECG and ventricular tachycardia on 24h Holter. In all, the anomaly was identified during the procedure. They were then submitted to implantation of ICD associated with stimulation (BIV), during the puncture of the left subclavian vein, the presence of PLSVC was found. It was decided to implant the ICD through the right subclavian vein and introduce the left ventricular lead into the left posterolateral vein through the deflectable sheath. Access to the coronary sinus was obtained by femoral access. Results: In all, the procedure was performed successfully. The procedure time was around 90 minutes. All patients (100%) did not show displacement of the electrodes, being discharged 24 hours after the procedure and in the clinical follow-up, the patients showed clinical and ejection fraction improvement, with an average EF from 24% to 42%. Conclusion: Although PLSVC is a rare and complex anomaly, the implantation of the ICD was possible through the right subclavian artery, not compromising the final result of cardiac resynchronization. 110865 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Treatment of Advanced Heart Failure in Octogenarians Through Implantation of a Multi-Site Cardioverter-Defibrillator ALFREDO AURELIO MARINHO ROSA FILHO3, Sara Carolline Gomes de Araujo Lima2, Lucas Brandao Cavalcante2, Jose Carlos de Souza Neto2, Alice Wanderley Rosa2, Marcelo Russo1, Gustavo Santiago1, Fabian Fernandes1, Lenine Angelo1, Flavio Loureiro1, Alfredo Aurelio Marinho Rosa1, Edvaldo Ferreira Xavier Junior1 (1) Santa Casa de Misericordia de Maceio - SCMM, AL; (2) Centro Universitario Tiradentes - UNIT/AL; (3) Hospital Universitario Professor Alberto Antunes - HUPAA/UFAL Background: Heart failure (HF) is considered the final stage of all heart diseases and with the increase in life expectancy of the population, octogenarian patients with HF can benefit from the implantation of a multisite cardioverter-defibrillator (ICD+). Objective: To present the results of the implantation of multi-site cardioverter-defibrillators in octogenarian patients with heart failure unresponsive to optimized clinical treatment. Material and Method: Between March 2010 and April 2022, 763 multisite cardioverter-defibrillators (ICD+CR-T) were implanted, of which 56 patients (7.34%) were octogenarians with 40 male patients (71.4%). Patients had HF with optimized drug treatment without adequate response, ejection fraction less than or equal to 32%, ventricular tachycardia and syncope. In this sample, they underwent implantation of the ICD+CR-T with access to the coronary sinus via the femoral route. Immediate success criterion coursing with QRS complex narrowing. Results: Of the 56 patients, forty-five (80.3%) responded satisfactorily to the therapy used, with a decrease in the number of hospitalizations and an improvement in the quality of life. Regarding the etiology of heart diseases: 38 (67.8%) were ischemic, 12 (21.4%) were chagasic and 6 (10.8%) had hypertensive heart disease. There were no intraoperative and postoperative complications and the main vein addressed for system implantation was the left posterolateral vein in 32 patients (57.1%). No displacement of electrodes was recorded. In the clinical follow-up, 22 pt (39.3%) received appropriate therapy for ventricular tachycardia. Survival was 100% at the end of 12 months in all patients undergoing ICD+CR-T implantation. Conclusion: It is therefore evident in the analyzed sample that the treatment of heart failure in octogenarian patients undergoing ICD+CR-T implantation showed a satisfactory response in terms of morbidity and mortality. 110870 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Comparative Study of Electrophysiological Parameters of Right Ventricular Stimulation Versus Stimulation of the Left Bundle Branch Area JOSE MIGUEL CAYO MONTES1, JOSE MIGUEL CAYO MONTES1, JUAN CARLOS ZERPA ACOSTA1, JOSE CARLOS PACHON MATEOS2, JUAN CARLOS PACHON MATEOS1, ENRIQUE INDALECIO PACHON MATEOS2, YVAN FLORES TARDIO1, CARLOS THIENE CUNHA PACHON2, CIBELE MATSUURA DE OLIVEIRA1 (1) HOSPITAL DO CORACAO; (2) SEMAP Introduction: Pacemaker (PM) implantation is the treatment of irreversible bradyarrhythmias, normalizing the heart rate, right ventricular apical pacing (RVAP) has been traditionally chosen, but it can induce ventricular dyssynchrony, resulting in a widening of the QRS complex duration. (QRSd) and left ventricular activation time (LVTA) increase, leading to heart failure and/or arrhythmias. In order to prevent these adverse effects, right ventricular septal pacing (RVSP) and more recently left bundle branch area pacing (LBBAP) of the bundle of His were developed, which reproduce more physiological activation of the cardiac conduction system. Objectives: The aim of this study is to compare the electrophysiological parameters of ventricular synchrony (QRSd, LVAT) and other parameters such as QRS axis, R-wave amplitude, threshold and impedance of RVAP, RVSP and LBBAP, in a group of patients with pacemaker implantation indication. Methods: Prospective and controlled study, which included 25 patients with indication for bicameral pacemaker implantation. Using radioscopy, first, the electrode is positioned in the position of the RAVP, using the electrogram recording system and the PM device programmer, unipolar stimulation is performed at this point and the electrophysiological parameters are recorded; QRSd, LVAT in V5 or V6, QRS axis, R wave, ventricular lead threshold and impedance. Afterwards, the ventricular electrode was positioned in the region of RVSP and LBBAP and the same parameters were measured. Results: Electrophysiological parameters. QRSd: RVAP: 162 +- 25 ms, RVSP: 145 +- 20 ms, LBBAP: 109 +- 17 ms (p < 0,05) LVAT: RVAP: 80 +- 11 ms, RVSP: 70 +- 16 ms, LBBAP: 60 +- 11 ms. (p < 0,04). QRS axis: RVAP: -56deg +- 10deg, RVSP: 45 +- 15deg, LBAP: 60 +- 11 ms (p < 0,04). Ventricular lead impedance: RVAP: 603 +- 20O, RVSP: 560 +- 25O, LBBAP: 805 +- 25O (p < 0,03). Threshold: RVAP: 0,75 +- 0.50V. RVSP: 0,75 +- 0.25V. LBBAP: 0.5 +- 0.25V (p < 0,05). R wave: RVAP: 10,1 +- 2 mV RVSP: 9,9 +- 3 mV LBBAP: 10,9 +- 6 mV(p: 0,06) There were no adverse events during the 6-month follow-up. Conclusion: The unipolar LBBAP achieved lower QRSd and LAVT, normal QRS axis, lower pacing thresholds, slight increase in ventricular lead impedance, there were no significant difference in the R wave sense compared to RVAP and RVSP. LBBAP is a safe technique that preserves ventricular synchrony, with better electrophysiological parameters compared to RVAP and RVSP, and could be considered as the first choice of ventricular pacing for patients. 111120 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Evaluation of Case Study Discussion in Cardiology Nursing: Instrument Validation JOAO PEDRO DA HORA SILVA BARROS1, Julya de Araujo Silva Monteiro1, Andressa Teoli Nunciaroni2, Renata Flavia Abreu da Silva2 (1) Universidade do Estado do Rio de Janeiro; (2) Universidade Federal do Estado do Rio de Janeiro Introduction: Active methodologies, such as case studies, are teaching strategies in nursing education, making the student an active agent in learning and the teacher a facilitator. Objective: To validate two evaluation instruments for case study discussion in cardiology nursing. Methods: Methodological, prospective, quantitative study, conducted remotely for content validation of measurement instrument. Two instruments were evaluated: Quantitative, with twenty-seven items and three aspects (Psychosocial, Intellectual and Human/Sensitive) and; Qualitative, with six questions addressing the learner's interest about case studies. Nurses with experience in cardiology for over two years were recruited and the instruments were structured in Google Forms(r), being available by link, with questionnaires in Likert Scale with an area for suggestions from experts. Data analysis was performed using Microsoft Excel(r) and validation was based on the calculation of the Content Validity Index (CVI). Items with at least 80% approval if more than six experts and 100% approval if less than six were valid. The study was approved by the institution's Research Ethics Committee under Opinion #4,126,925 on July 1, 2020. Results: The data collection took place in October 2020, obtaining 7 responses from jurors with experience ranging from 4 to 30 years; 3 specialists, 2 masters, and 2 PhDs. In instrument 1, 7 items were not validated, namely: 2 on the Intellectual Aspect and 5 on the Human/Sensitive Aspect; in instrument 2, only 1 item on Pertinence. After changes, a new consultation was made, and 7 responses were obtained, validating all items of the instruments. When calculating the CVI of the instrument (CVI-I), the comprehensiveness, clarity and pertinence were: instrument 1 = 0.99, 1 and 0.97 and; instrument 2 = 1, 0.97 and 1. The validation occurred in Portuguese, not being translated so that there would be no reduction in its characteristics. The simultaneous use of the instruments is mandatory. Some limitations: reduced access to hospitals/universities by COVID-19 and no testing with the public. Conclusion: The validated instruments can be used to evaluate learning through case studies in cardiology. With the interpretation of the results of the instruments, the teachers will be able to recognize the weaknesses and form strategies to overcome them, besides being used in actions of permanent education. 110895 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS The Neutrophil-to-Lymphocyte Ratio on Admission as Important Predictor of In-Hospital Mortality in Acute Myocardial Infarct Patients VISAKHA REVANA IRAWAN1, Frans Wantania2, Janry Pangemanan2 (1) Department of Internal Medicine, Faculty of Medicine, Sam Ratulangi University/Prof. dr. R. D. Kandou General Hospital, Manado, Indonesia; (2) Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Sam Ratulangi University/Prof. dr. R. D. Kandou General Hospital, Manado, Indonesia Background: The neutrophil-to-lymphocyte ratio (NLR) in peripheral blood has recently been able to act as a biomarker that can predict worse clinical conditions ranging from infectious diseases to cardiovascular diseases. Objective: The study aimed to determine the optimal cutoff level of NLR level to predict in-hospital mortality in acute myocardial infarction (AMI) patients. Methods: We analyzed the data characteristics of 332 consecutive cases of AMI patients admitted in Prof. dr. R. D. Kandou General Hospital, retrospectively, from September 2020 to December 2021. Patients with acute infections, HIV/AIDS, who used corticosteroids in the last three months, and antibiotics in the last 24 hours were excluded. NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count (CBC) on hospital admission. Furthermore, the optimal cutoff level of NLR was analyzed using ROC curves to discriminate survivors versus non-survivors during hospitalization. Results: The value of NLR in predicting in-hospital death (AUC = 0.88, p = 0.0001) was higher than the platelet-lymphocyte ratio (PLR) (AUC = 0.79, p = 0.0001), the neutrophil-monocyte ratio (NMR) (AUC = 0.61, p = 0.075), and the lymphocyte-monocyte ratio (LMR) (AUC = 0.17, p = 0.0001). The optimum cutoff NLR level to predict in-hospital mortality was 7.36, with a sensitivity 72% and a specificity of 90.55%. Patients with NLR levels >=7.36 had a higher probability of mortality when comparing with those who with NLR levels <7.36 (OR = 24.65, 95% CI (9.5-63.94), p = 0.0001). Conclusions: NLR could be an early and important predictor of in-hospital mortality in AMI patients. 111347 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Standard Treatment Protocols for the Pharmacological Management of Hypertension: Comparison with the Major Clinical Practice Guidelines Recommendations GAUTAM SATHEESH1, Rupasvi Dhurjati1, Abdul Salam2 (1) The George Institute for Global Health, Hyderabad, India; (2) The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia Introduction: Globally, there are large gaps in the diagnosis, awareness, treatment, and control of hypertension. Using evidence-based standard treatment protocols (STPs) may improve hypertension treatment and control. Objective: 1. To summarize major guidelines recommendations for the pharmacological management of hypertension. 2. To identify, characterize and compare available hypertension STPs with the major guidelines. Methods: We summarized recommendations on the pharmacological management of hypertension from four major hypertension guidelines: American Heart Association, European Society of Cardiology, World Health Organization (WHO), and International Society for Hypertension. STPs were identified from websites of WHO, Resolve to Save Lives, Pan American Health Organization and through expert consultations. We defined hypertension STP as series of steps recommended for treating hypertension with information on target patient group (age, comorbidities, race etc.), blood pressure (BP) thresholds for treatment initiation and intensification, BP targets, drugs/classes for each step, follow-up frequency, target time for BP control, and combination therapy/single-pill combinations. Results: All guidelines, except American, presented a stepwise treatment approach and recommended initiation with single-pill combinations in most patients. All guidelines recommended renin-angiotensin-system inhibitors (RASi), thiazide-type diuretics (TZD), or calcium channel blockers as first-line therapy. Except WHO, no guidelines specified individual drugs or doses. Further, WHO and American guidelines did not mention a target time for BP control. All identified STPs (n = 36) presented a stepwise approach, and 86% (n = 31) consisted of 5 or more steps. Majority (86%) recommended calcium channel blockers as initial therapy, and RASi were the second choice in 69%. TZD was introduced as a third line agent in 72% of STPs, second line in 14%, and first line in 11%. Only eight STPs recommended initiation with combination therapy, and only two recommended single-pill combinations. Contradictory to guidelines, 39% of STPs recommended dose-increase if desired BP control is not achieved. No STPs mentioned a target time for BP control. Conclusion: Several deviations from the major guideline recommendations were observed in the identified STPs. Developing optimal, evidence-based, and context-specific STPs is vital to control hypertension, especially in countries with limited resources. 111165 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Development of Cardiomyopathy in Patients After Liver Transplantation for Hereditary Transthyretin Amyloidosis FERNANDO SARAIVA CONEGLIAN1, Fernando Saraiva Coneglian1, Flavio Henrique Valicelli1, Fernanda Fernandes Souza1, Ajith Kumar Sankarankutty1, Wilson Marques Junior1, Caroline Lavigne Moreira1, Minna Moreira Dias Romano1, Pedro Manoel Marques Garibaldi1, Rodrigo Tocantins Calado de Saloma Rodrigues1, Marcus Vinicius Simoes1 (1) Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto Introduction: Liver transplantation (LT) is an alternative treatment for patients with familial amyloidotic polyneuropathy (FAP), correctly renamed hereditary transthyretin (hATTR) amyloidosis, and is associated with a significant improvement in survival. However, some patients may exhibit progression of the disease latelly, with eventual cardiac involvement. There are few reports on the most common cardiac manifestation in these cases. Objective: To describe the clinical evolution and cardiac involvement in patients who underwent liver transplantation for hATTR in a single interdisciplinary Amyloidosis center. Methods: Observational study of cohort with 8 patients undergoing LT after the diagnosis of hATTR, considering cardiovascular symptoms, ECG, Echocardiogram and therapeutic management. Results: All 8 patients had a diagnosis of hATTR with early-onset V30M mutation, 6 were male (75%). The mean follow-up after LT was 13.5 + 3.9 years and the age at the moment of evaluation was 49.3 + 6.2 years. Cardiovascular manifestations occurred in 4 patients (50%), corresponding in all cases to symptomatic bradycardia with Sinus Node Disease (SND) and need for permanent pacemaker (PP) implantation, with the mean period of cardiovascular manifestation being 14 years. All patients with DNS exhibited symptoms of severe autonomic neuropathy with symptomatic postural hypotension. Only 2 patients(25%) developed echocardiographic alterations compatible with myocardial infiltration by CA and significant increase in the thickness of the interventricular septum (13-15 mm), 1 patient have developed manifestations of heart failure (HF) that started 16 years after LT. This same patient had DNS and PP implant 4 years before the onset of HF. Conclusion: Our results indicate a high prevalence of late development of cardiac organic involvement after liver transplantation in patients with hATTR due to V30M mutation. The preferred form of manifestation of heart disease is symptomatic bradycardia by SND requiring PP implantation. There seems to be an association between the intensity of autonomic denervation and SND, suggesting a pathophysiological link between these abnormalities. 110900 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Opposite Effects of Dapagliflozin and Glibenclamide on Diastolic Function in Patients with Diabetes: Randomized Controlled Trial (Addenda-BHS2) SHEILA TATSUMI KIMURA MEDORIMA1, Daniela Camargo Oliveira1, Ikaro Soares Santos Breder1, Vaneza Lira Waldow Wolf1, Luiz Sergio Fernandes de Carvalho1, Alexandre Anderson de Sousa Munhoz Soares1, Joaquim de Paula Barreto Fonseca Antunes de Oliveira1, Daniel Batista Munhoz1, Jessica da Silva Cunha Breder1, Wilson Nadruz Junior1, Thiago Quinaglia Araujo Costa Silva1, Andrei Carvalho Sposito1 (1) Atherosclerosis and Vascular Biology Laboratory (Atherolab), Cardiology Department, State University of Campinas (Unicamp), Campinas, SP, Brazil. Dapagliflozin significantly reduced cardiovascular death and heart failure endpoints, however sulfonylureas and metformin are the only oral antidiabetics available in Brazilian Primary Care Public Health System. This trial was planned to evaluate their effect on diastolic function and to investigate possible mechanisms underlying this change. Methods: The Assessment of Dapagliflozin effect on Diabetic Endothelial Dysfunction of brachial Artery - Brazilian Heart Study 2 trial is an investigator-initiated prospective clinical trial, single-center, active-controlled, open-label, phase-4 randomized trial. High cardiovascular risk patients with type 2 diabetes were randomized to 12-week treatment with Dapagliflozin (DAPA) or Glibenclamide (GLIB) on top of Metformin, in glucose-lowering equivalent regimens. Echocardiogram was performed at randomization and at 12 weeks. Serum nitrate was analyzed by NO chemiluminescence analyzer. Results: 97 patients completed the study, including 61% males, median age 59(10) years, mean LVEF 62.9% +- 8. After 12weeks, E/e'ratio difference significantly reduced in DAPA group, while increased in GLIB arm [-0.17(1.9) vs 0.87(2.3), p = 0.001]. Tissue Doppler e' velocities did not change significantly, but E velocity increased with GLIB [0(19.7) vs 4.0(16.0), p = 0.016]. LV mass and LV septum reduced in DAPA group, although without statistical significance. Exploratory secondary analysis was performed with clinical variables tested in multivariable binary logistic regression analysis, with E/e' ratio improvement as dependent variable. Nitrate raising was an independent predictor of diastolic function improvement (B = 1.098; p = 0.024; Exp(B) = 2.999), adjusted for age, sex, body surface area and randomization group. This multivariable model classifies correctly 70,1% of the patients (model R-squared = 0,27; p-value < 0,001). Conclusion: Dapagliflozin significantly improves diastolic function by reducing E/e' ratio, while Glibenclamide worsens. In our study, E/e' improvement was significantly predicted by serum nitrate raising after 12-weeks, offering important clues on the pathophysiology evolved in SGLT2 inhibitors myocardium protective effect. 110947 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Hypertrophic Cardiomyopathy: Identification of the Molecular Profile and Treatment of Phenocopies ANABEL LIMA VIEIRA1, Renan Figueiredo de Freitas1, Maria Beatriz Siqueira de Araujo4, Sergio Jose Siqueira de Araujo3, Andrea Virginia Ferreira Chaves2 (1) Hospital Agamenon Magalhaes, Recife, PE; (2) Servico de Referencia em Doencas Raras - RARUS, Recife, PE; (3) UniNassau, Recife, PE; (4) Faculdade Pernambucana de Saude, Recife, PE Introduction: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease (1:200). The development of genetic panels for cardiomyopathies has allowed for the diagnosis of phenocopies, the receipt of adequate genetic counseling and, most importantly, the identification of diseases with specific treatment. Objective: To present the genetic characterization of a group of patients (pts) with an echocardiographic diagnosis of HCM. Methods: This was a cross-sectional observational study that looked at pts who had been diagnosed with HCM and had a molecular panel for HCM. The genes analyzed were cardiac a-actin, desmin, filamin C, alpha galactosidase A, lysosomal-associated membrane protein 2, myosin-binding protein C, cardiac b-myosin heavy chain, myosin light chain 2, myosin 3, myopaladin, phospholamban, Protein kinase A g subunit, non-receptor tyrosine-protein phosphatase type 11, troponin C1, troponin I3, troponin T2, a-tropomyosin 1 and transthyretin. Results: The panel was performed on 25 pts with HCM. The age ranged from 13 to 91 years, mean 39.3 years. Regarding gender, 52% were women. Variants were found in cardiac b-myosin heavy chain genes (sarcomeric, chromosome 14, autosomal dominant and recessive) in ten pts (40%), filamin C in four pts (16%), myosin-binding protein C in three pts (12%), desmin in two pts (8%), myosin light chain 2 in one pts (4%), a-tropomyosin 1 (TPM1) in one pts (4%), troponin T2 in one pts (4%), non-receptor tyrosine-protein phosphatase type 11 (Noonan syndrome - phenocopy, chromosome 12, autosomal dominant) in a pts (4%), lysosome-associated membrane protein 2 (Danon's disease - phenocopy, X chromosome) in a pts (4%), alpha galactosidase A (Fabry's disease - phenocopy, X chromosome) in one pts (4%). In one pts two mutations were found and in another three concomitant mutations. In one pts, no mutation was identified. Conclusion: The molecular panel was used to provide adequate genetic counseling to the pts. Three pts with HCM related phenocopies (Noonan syndrome, Danon's disease, and Fabry's disease) were identified. The diagnosis of Fabry disease allowed for the recommendation of specific treatment, which had a direct impact on the natural history of this pts and their families. Because the panel used was limited to 18 genes, no mutations were found in three pts. Expanded panels improve the probability of genotype identification and the possibility of effective therapy. 110957 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOGERIATRICS Thyroid Dysfunction and Presence of Atrial Fibrillation in Elderly Patients with Heart Failure ANABEL LIMA VIEIRA1, Marina Souto da Cunha Brendel Braga1, Amanda Valerio Galindo1, Caio Correia da Silva1, Rafael Buarque de Macedo Gadelha1, Matheus Dantas Soeiro2, Sabrina Barreto Braga Pires2, Jessica Myrian de Amorim Garcia1, Francisco Alfredo Bandeira e Farias1 (1) Hospital Agamenon Magalhaes, Recife, PE; (2) Faculdade Pernambucana de Saude, Recife, PE; (3) Universidade de Pernambuco, Recife, PE Introduction: Thyroid hormones have both direct and indirect effects on cardiac cells, so both excess and deficiency will influence the cardiovascular system. Atrial fibrillation (AF) is one of the cardiac manifestations of thyroid dysfunction (TD), particularly hyperthyroidism, and arrhythmia with clinical significance is more common in the context of thyroid diseases. Objectives: To assess the relationship between thyroid dysfunction and the presence of atrial fibrillation in elderly patients with heart failure. Methodology: An observational cross-sectional study. The medical records of 118 patients 65 years old admitted to the cardiology ward with HF from August 2020 to October 2021 were analyzed. For qualitative variable comparisons, SPSS v.25.0 was used, and the assumed significance level was 5%; for quantitative variables AF x TD, the chi-square test was used. Results: There is a mean age of 72.8 years (ranging from 65 to 96 years), with the majority of patients being male (54.2%). There are 36 patients (30.5%) with TD present. 47.2% of these patients are male, 97% have Systemic Arterial Hypertension, 46.9% have Diabetes Mellitus (DM), and 25% are pre-DM. Nonetheless, 38.9% have HFrEF, 19.4% have HFrEFi, and 41.7% have HFrEFp, with an average LVEF of 48.16% (standard deviation: 16.8); 5.7% have coronary artery disease, and 26.3% have a history of stroke. In the TD group, 32 patients (88.88%) had subclinical hypothyroidism, while 4 (11.11%) had clinical hypothyroidism. In this group, the mean thyroid-stimulating hormone (TSH) level was 11.26, with (standard deviation: 13.69). 12 patients (33.3%) in the TD group had AF. Only 11 (13.4%) of the non-DT group had AF. The mean TSH in AF patients was 8.50, with a standard deviation of +-14.7, compared to 4.03, with a standard deviation of +-6.17 in non-AF patients (t(116) = 2.267; p = 0.013). The comparison of TD and AF revealed a close relationship between the two variables: 10.2% of the elderly with TD had AF, while only 9.3% of the sample (69.5%) did not have TD (Chi-Square = 6.325a; p = 0.012). Conclusions: According to the study sample, there is a statistically significant relationship between thyroid dysfunction and atrial fibrillation in elderly HF patients, corroborating what has previously been established in the literature. Among the possible thyroid dysfunctions, this study found a stronger link between AF and hypothyroidism, both clinical and subclinical. 110972 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY The Neurodevelopment of Infants with Congenital Heart Disease in Southern Brazil: A Sample Characterization of a Pilot Study RITA CASSIANA MICHELON2, Caroline Engster da Silva2, Ludimila Silveira Parker Lopes1, Claudia Costamilan Paes2, Fernanda Lucchese1 (1) Santa Casa de Misericordia de Porto Alegre (ISCMPA)/Hospital da Crianca Santo Antonio (HCSA); (2) Instituto de Cardiologia/Fundacao Universitaria de Cardiologia (IC/FUC) Introduction: Congenital Heart Disease (CHD) has a prevalence of about 1 case per 100 live births nationwide in Brazil. Infants with CHD are at greater risk of having developmental delays. In 2012, the American Heart Association (AHA) proposed guidelines for the evaluation and intervention of neurodevelopmental delays in infants with CHD. Multidisciplinary early evaluation and interventions can significantly improve the course of the development of a child with CHD, preventing neurodevelopmental sequelae and increasing quality of life, adaptive skills, and academic and professional achievements later in life. Objective: To present data on the neurodevelopment of infants with CHD participating in a multidisciplinary research clinic seeking to develop low-cost early intervention protocols in Brazil. Method: Fifty-nine infants with CHD under the age of 42 months were recruited from a convenience sample at the Pediatric Cardiology Outpatient Clinic of a reference hospital in Southern Brazil. The information was gathered through parental questionnaires. Infant development was measured by the Bayley-III Infant and Toddler Development Scale. Results: Of the 59 infants recruited, there were 17 drop-outs due to non adherence, schedule incompatibility, fatigue during the assessment or death. Forty-two infants (28 female, at the average age of 10 months). Forty-three infants who underwent surgery had on average 2 procedures, ranging between 1-5 surgeries. Sixty-seven percent of the infants were cyanotic. The average length of hospital stay was 31 days (X-XX range), and eight were preemies. The developmental findings showed that 41% of infants were borderline or delayed in the Cognitive, 31% in Receptive Language, 29% in Expressive Language 29%, 36% in Fine Motor, and 67% in the Gross Motor domains. Conclusion: This study showed high rates of developmental delay in infants with CHD from a public (SUS) outpatient clinic in Southern Brazil. In particular, almost 70% of the sample was at risk or had a delay in gross motor development. These data are congruent with previous research that have shown developmental delays in infants with CHD, in particular gross motor deficits. This evidence corroborates with AHA's guidelines, and supports the need for multidisciplinary early evaluation and intervention to prevent neurodevelopmental sequelae in low-income infants with CHD in Brazil. 111366 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Pericardial Involvement is More Transient Than Myocardial in Patients After COVID-19 Infection Detected by Cardiovascular Magnetic Resonance MARILIA MIGUEL DA SILVEIRA1, Sergio Augusto Yukio Hissayassu1, Isabela Ramos Ali Ganem1, Livia Hirayama1, Raiza Silveira da Costa1, Carlos Alexandre Vieira Gomes1, Tiago Augusto Magalhaes1, Adriano Camargo de Castro Carneiro1, Carlos Eduardo Elias dos Prazeres1, Juliana Matsumoto Bello1, Valeria de Melo Moreira2, Carlos Eduardo Rochitte1 (1) Hospital do Coracao (Hcor); (2) Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Background: Cardiovascular complications in Covid-19 is prognostic. Myocarditis and pericarditis can be precisely detected by cardiovascular magnetic resonance (CMR) and present early and/or later (Covid-19 long). Myocardial and pericardial evaluation by CMR in routine clinical practice is scarce. Therefore, we sought to investigate cardiac abnormalities by advanced CMR including subtle tissue chances in myocardium and pericardium. Methods: We included 303 consecutive patients with confirmed prior Covid-19 diagnosis referred to CMR, performed in a 1.5T scanner (Sola CV edition, Siemens Healthineers) with cine-MR, late gadolinium enhancement (LGE), T1(MOLLI), T2 maps and extracellular volume measurements (ECV) using standard parameters. Early-CMR or late-CMR if CMR was defined as before or after 60 days of the infection, respectively. Results: From the 303 patients, 120 (39.9%) were female, mean age was 47.6 +- 13.8 years and mean body mass index of 27.7 +- 4.9. Symptoms were present in 87 patients (28.7%). Mean interval between Covid-19 infection and CMR study was 155.0 +- 138.6 days for the entire study group, with 78 patients (30.3%) with early-CMR. Myocardial LGE (mLGE) was present in 60 patients (19.9%), with 14.1% in early-CMR and 21.8% in late-CMR (p > 0.05). However, pericardial LGE (pLGE) was more frequent in early-CMR than late-CMR (9.0 vs. 2.8%, p = 0.049). The presence of mLGE was similar between symptomatic vs asymptomatic patients (17.7 vs. 20.8%, p > 0.05). Patients with risk factors for coronary artery disease (including obesity) had significantly more mLGE than those without (26.1 vs. 15.9%, p = 0.039). Native T1 and T2 values were higher in patients with CAD (1041 +- 31 vs. 1005 +- 3.8 and 46.7 +- 2.2 vs 44.3 +- 0.3, p = 0.024 and 0.039, respectively), but ECV was similar. No differences were seen in maps and ECV values between early and late-CMR. Thus, mLGE has similar distribution for symptomatic/asymptomatic and early/late phases after infection. However, pLGE was significantly more frequent in the first 60 days after infection. CAD patients had higher T1/T2 myocardial maps. Conclusions: CMR was able to detect subtle myocardial and pericardial changes in patients after Covid-19. Myocardial involvement was similar regardless of symptoms and time after infection, while pericardial involvement was detected more frequently before 60 days of the infection. This might indicate that pericardial involvement is more transient than myocardial involvement. 110983 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY An Analysis of the Epidemiology of Conduction Disorders and Cardiac Arrhythmias in Brazil in the Last 5 Years PEDRO HENRIQUE ALMEIDA WAROL 1, PEDRO HENRIQUE ALMEIDA WAROL1, TALLES AYRES LIMA2, ROMULO RODRIGUES BADINI3, NAJLLA DE SALIM RIBEIRO4, MARIANNA RAMALHO DE SOUSA1, EMILIO PANDELO LIMA1, EMILIO CONCEICAO DE SIQUEIRA1 (1) UNIVERSIDADE DE VASSOURAS; (2) UNIVERSIDADE ESTACIO DE SA; (3) UNIVERSIDADE UNIGRANRIO; (4) FACULDADE DE MEDICINA DE PETROPOLIS Cardiovascular diseases (CVD) are the leading cause of death in Brazil. Among such diseases, there are Conduction Disorders and Cardiac Arrhythmias (CBD), electrical changes in the heart that cause changes in its normal rhythm. Even though it is configured as a public health problem, there is a scarcity in the literature regarding the epidemiological aspects of hospitalizations and deaths of this disease, and its analysis is essential in order to prepare health teams to deal with BED. A systematic review of the literature was carried out together with the descriptive, cross-sectional and observational collection of data available in DATASUS - Hospital Information System of the SUS (SIH/SUS) - from 2017 to 2021, evaluating hospitalizations, deaths and pattern of patients: age group, sex and self-reported color/race. In the analyzed period, there were 316,939 hospitalizations for BED with a total expense of 1,391,918,003.70 reais, with 47.5% of these hospitalizations in the Southeast region. The most affected sex was male, with 52.5% of hospitalized cases. The age group with the most hospitalizations was over 50 years old, with emphasis on the 70 to 79 years old group, which corresponded to 25.8% of the total. When analyzing color, white was the most affected with 45.7% of the total, however 20% of hospitalizations did not have this information. As for deaths, in the analyzed period, there were 40,193, with a predominance of males, which corresponded to 54.3% of the total deaths from BED. The age group with the highest mortality was over 60 years, with emphasis on individuals aged 80 years and over, who accounted for 24.8% of deaths. There was an increase in mortality, which in 2017 was 6,854 and in 2021 it reached 8,664. TCACs represent a serious public health problem with high morbidity and mortality. Because of this, and the increase in mortality expressed in the years analyzed by the research, a new dynamics in health is essential. This dynamic must be guided by prevention and health promotion, with effective monitoring carried out by Primary Health Care in association with the care provided by the cardiologist, in order to avoid the development and worsening of these diseases. 111004 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Analysis of the Results of Minimally Invasive Mitral Valve Surgery in a Brazilian Health Service in the Year of 2021 DANIEL DE MAGALHAES FREITAS1, Artur Henrique de Souza1, Joao Alberto Pansani1, Max Weyler Nery1, Patricia Ferreira Demuner1, Stanlley de Oliveira Loyola1, Mauricio Lopes Prudente1, Debora Rodrigues1, Larissa Xavier Alves de Oliveira1, Fernando Araujo Cintra Canedo1, Giulliano Gardenghi1 (1) Hospital Encore Introduction: The feasibility of minimally invasive mitral valve surgery (MIMVS) has been proven extensively and many centers around the world have been using this technique as a standard approach. Some advantages of the minimally invasive technique, compared to the traditional median sternotomy, are the blood loss reduction, lower morbidity, and shorter intensive care unit and in-hospital stay. Objective: In this study we analyzed the results of MIMVS performed at our institution in the year of 2021 and compare with data from the international literature. Methods: 13 patients were submitted to MIMVS. At our institution, a femoral cannulation is utilized to establish cardiopulmonary bypass; and the incision was made at third or fourth intercostal space starting at the mid-subclavicular line with a length of 5-7 cm. The myocardial protection is done with cold-blood cardioplegia. Data were collected from the patients records and tabulated and analyzed in the Excel software(r). We used Mitral Valve Academic Consortium safety definitions for comparison purposes. Results: From the 13 cases, 11 (84,6%) were valve replacement and 2 were of valve repair. Age mean was 59,6 years (+-14); 9 (69,2%) were at low risk by STS score, 3 were at medium risk (23,2%) and 1 (7,6%) at high risk. The 30-day complications analysis are shown in table 1. Conclusion: Our results are consistent with the world literature corroborating the feasibility and safety of the technique. 111020 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION A Force to be Reckoned With: The Top 75 Twitter Influencers in Cardiac Imaging NAJAH KHAN1, Bindu Chebrolu1, Nadeen N. Faza1 (1) Houston Methodist Hospital Introduction: Twitter influencers exchange information and stimulate discussions from a breadth of expertise. Cardiovascular imaging with echocardiography (ECHO), cardiac computed tomography (CCTA), single-photon and positron emission tomography (SPECT and PET), and cardiac magnetic resonance imaging (CMR) has gained momentum through social media. Objectives: To analyze demographics of top Twitter influencers and imaging modalities they discuss on Twitter. Methods: Twitter topic scores for "cardiac imaging" (CCTA, CMR, SPECT, and PET) and "echocardiography" were collated for individual accounts on Feb 6, 2022 using the Cronycle monitoring platform (integrated with the Right Relevance application programming interface), generating top 75 influencers. Cardiovascular board certifications were confirmed via country-specific board-certifying organizations. Occupation, gender, location, and imaging modalities discussed by influencers were confirmed via Twitter biographies. Influencers' academic influence (h-indices) from Scopus were correlated to their topic scores. Results: Majority influencers were male (73%) and board-certified cardiologists (87%), followed by non-cardiovascular physicians (9%), and non-physicians (4%). The most discussed imaging modality was echocardiography by 40% of top influencers, followed by CMR (28%), CCTA (23%), and Nuclear/PET imaging (9%). Most influencers reside in the United States (61%) followed by the United Kingdom (17%), Canada (4%), Italy and Portugal (3%), and other countries (Spain, Romania, Serbia, Peru, Germany, Chile, Columbia, Brazil, and Australia, 1% each). There was a positive correlation between the h-index and Twitter topic score (r = 0.3562, p = 0.0009). Conclusions: While most top influencers in cardiac imaging are board-certified male cardiologists in the United States, other influencers consist of international cardiologists, non-cardiovascular physicians, and non-physicians. There is a vast global representation of cardiac imaging influencers, showcasing the reach and expansive growth of the field. These findings emphasize the diverse representation of cardiac imaging influencers on Twitter, hopefully changing the landscape of this field. 111022 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Peripheral Arterial Disease as a Predictor of Coronary Arterial Disease and Prognosis in Patients with Stage 5 CKD Undergoing Hemodialysis DANIEL BATISTA CONCIECAO DOS SANTOS2, Luis Henrique Wolff Gowdak2, Jose Jayme Galvao de Lima2, Luiz Aparecido Bortolotto2 (1) Universidade de Sao Paulo; (2) Instituto do Coracao Introduction: There is a need of a simple, inexpensive and reliable noninvasive testing to predict coronary artery disease (CAD) in CKD patients, a population with the higher prevalence of CV events and death. Object: This study analyzed the association between peripheral arterial disease (PAD) and CAD in patients with stage 5 CKD on dialysis. Methods: This was a prospective and observational cohort study in 201 CKD patients on hemodialysis. PAD was defined by either the absence of peripheral arterial pulse by palpation or by >=50% narrowing by ultra sound Doppler (USD) and CAD by angiography (>=70% narrowing). Results: Palpation and USD predicted the occurrence of PAD (P = 0.0001, OR = 27.37). CAD was observed in 45% of patients with PAD (by palpation) and in 60% by USD. Absence of pulse by palpation predicted CAD with a sensitivity of 55% and a specificity of 76%; USD showed a sensitivity of 62% and specificity of 60%. The risk of combined serious CV events and death was significantly higher in individuals with PAD diagnosed by palpation but not by USD. PAD assessed by palpation also correlated with the occurrence of multivessel CAD and with the probability of coronary intervention. Conclusion: There is a high prevalence of CAD in patients with PAD. Palpation may be used instead of USD for the diagnosis of PAD because is inexpensive and easier to use. Both methods presented a moderate utility to predict CAD but the diagnosis of PAD by palpation was a predictor of combined cardiovascular events and death and was also associated with the severity of CAD and the probability of indication of coronary intervention. 111043 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Resources Management in Brazilian Public Health System: How to Define Priority for Cardiologist Consultation Based on Telecardiology, Risk Classification and Diagnostic Groups? SHEILA TATSUMI KIMURA MEDORIMA1, Eduardo Monteiro Diniz Junqueira1, Ana Cristina Serodio1, Maria Fernanda Murijo Righi Turatti1, Fernanda Melo Gomes1, Carolina Rosa Queiroz Fulas1, Valeria Cristina Jodjahn Figueiredo1 (1) Municipal Health Department (SMS-Campinas), Prefeitura Municipal de Campinas Introduction: The COVID-19 pandemic required special management of health services, once outpatients visits were suspended in most units during the lockdown. In Campinas-SP, since 2006, cardiology matrix support is acknowledged by primary health care as a service to case discussion, EKG evaluation and shared care. Since 2019, our team offers telecardiology through institutional e-mail, which acquired great importance during Pandemics. Objective: Evaluate the content of these e-mails, quantifying diagnostic groups with priority risk classification. Methods: This is a cross-sectional observational study, using data from service registry produced by cardiologists while evaluating cases received from e-mail. This research has been approved by ethics committee. Results: In a total of 2224 cases discussed along 2021, 22.8% had missing data, 10.8% were high risk CAD or unstable CAD, 9.4% had acute HF symptoms, 6.4% intermediate risk chest pain, 5.5% structural chronic heart disease, 4.7% paroxysmal supra ventricular tachycardia and 4.1% had abnormal heart murmur. There were 1089 patients (49% of the cases) classified as priority. More priority cases were in the following diagnostic groups: acute atrial fibrillation (AF) (90.2% priorities), high risk CAD or unstable CAD (90.0% priorities), thromboembolic event (87.5% priorities), syncope (78.0% priorities), post-COVID cardiovascular complications (72.0% priorities), structural chronic heart disease (74.6% priorities), acute HF symptoms (72.7% priorities) and chronic AF (69.2% priorities). Conclusion: Telecardiology in Public Health System of Campinas-SP was a successful experience during the COVID-19 pandemics, allowing to evaluate clinical criteria to guide priority risk classification for cardiology consultations, ensuring equity. 111049 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Telecardiology is a Management Tool for Specialized Care in the Brazilian Public Health System, Campinas-SP SHEILA TATSUMI KIMURA MEDORIMA1, Eduardo Monteiro Diniz Junqueira1, Ana Cristina Serodio1, Maria Fernanda Murijo Righi Turatti1, Fernanda Melo Gomes1, Carolina Rosa Queiroz Fulas1, Valeria Cristina Jodjahn Figueiredo1 (1) Municipal Health Department (SMS-Campinas), Prefeitura Municipal de Campinas Cardiology matrix support (CMS) is offered to Primary Care services since 2006 in Campinas-SP, allowing closer relationship with the specialists. In 2019, telecardiology was the method used to expand this proposal, through the institutional e-mail for case discussion, clinical orientation, receiving ECG requiring reports and risk classification for cardiology consultation. This method allowed Specialized Care to meet the needs of Primary Care during the COVID-19 Pandemic, allowed priority access to urgent cases and contributed to continued education of Primary Care in Cardiology. Objective: Characterize the CMS performed in Brazilian Public Health System (SUS), Campinas-SP. Methods: This is a cross-sectional observational study with data registered by cardiologists while evaluating clinical cases discussed via e-mail. This research has been approved by ethics committee. Results: In a total of 2224 cases discussed along 2021, the median age was 61 years, most female (N = 1136,51%). A total of 1089(49%) was classified as priority, 538(24%) as intermediate and 46(2%) as low risk. There were 546(24%) referrals with incomplete data, 381(17%) had insufficient data, 809(36%) proposed shared patient care instead of referring the patient to the specialist, 797(36%) received orientation regarding therapeutic adjustments or complementary investigation. The CSM offered cardiology consultation for 477(21%), echocardiography for 303(14%) and exercise testing for 110(5%). Conclusion: Telecardiology was consolidated in Specialized Care at the SUS in Campinas-SP during the COVID-19 Pandemic, allowing quick access from Primary Care to cardiology support. This data will contribute with the analys of the impact of this format of Specialized Care and for future improvements. 111054 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION State Supported Remote Consultations of Cardiologists in Latvia During the Covid Pandemic - Experience and Opportunities EMMA SOKOLOVA1, Aleksandra Jeniceka2, Ieva Bikava3 (1) Riga Stradins University, University of Latvia, RISEBA, Riga East University Hospital, Pauls Stradins Clinical University Hospital; (2) Riga Stradins University, RISEBA; (3) Riga Stradins University Introduction: Available data on the doctor-patient remote consultations all over the world shows that those are mostly provided by radiologists, psychiatrists and cardiologists. The regulatory framework of each country, the procedure for organizing and payment procedure for the specialists, the legal aspects and the complexity of the medical sector create specific conditions and the need to develop a model and procedure for providing remote consultation appropriate to each country and institution. Objectives: The aim of the study was to find out, summarize and analyze the experience of state paid remote consultation of cardiologists in Latvia during the year 2021, identify problems and develop recommendations for safe and effective remote specialist-patient and specialist-specialist consultation in cardiology. Methods: The study was conducted through semi-structured interviews with cardiologists of PSCUH, data provided by NHS of Latvia and Specialized Medicine Center (unit of State EMS). Results: The total number of state provided teleconsultations was 2 884 632, from them only 2194 (0,8%) patient-cardiologist consultations were conducted, which for 1,9 billion of Latvian population is a very low indicator. Remote patient-cardiologist consultations remained under 0,1% - compared to consultations of doctors of other specialities. The majority of cardiologists indicated that the first consultations could not be performed remotely over the phone. At the specialist-specialist level, the demand is stable, with around 1,100 consultations each year and accounting for about 20-25% of the total number of remote consultations. Conclusions: The main obstacles to remote visits, especially for first-time visits, are related to two problems: 1) the specialist does not have access to all examinations and results of the patient, and 2) it is not possible to make an objective assessment of the patient. A video call is recommended for remote consultations, as it is able to provide more additional information and patient evaluation options. Patient monitoring through remote consultations would be possible if visits are sufficiently regular (every 3 or 6 months), the patient is compliant, the patient's condition has not significantly deteriorated, and the necessary examinations and analyzes have been performed and are available to the doctor. At present, procedures have not been developed and defined at the national level for the implementation of telephone consultations. 111073 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Economic Evaluations of Prevention, Screening, Diagnosis, and Medical and Surgical Management of Rheumatic Heart Disease: A Systematic Review DOMINIQUE VERVOORT1, Rachel Livergant2, Maryam Shams3, Niraj S Kumar4, Sameer Hirji5, Bobby Yanagawa1 (1) Division of Cardiac Surgery, University of Toronto; (2) Office of Global Surgery, Department of Surgery, University of Alberta; (3) Department of Medicine, Stanford University; (4) Department of Medicine, University College London Medical School; (5) Department of Surgery, Brigham and Women's Hospital, Harvard Medical School Introduction: Rheumatic heart disease (RHD) affects over 30 million people globally and remains one of the most underfunded conditions in global health relative to its disease burden. The lack of access to primary, secondary, and tertiary prevention and care for the majority of the world's population contributes to these disparities and is a result of a poor understanding of the socioeconomic value of interventions to prevent and manage RHD. Here, we evaluate the current literature to assess economic evaluations of the prevention, screening, diagnosis, and medical and surgical management of acute rheumatic fever (ARF) and RHD. Objective: The objective of this study is to identify the current knowledge and gaps surrounding the cost-of-illness of ARF/RHD and the cost-effectiveness and cost-utility of prevention or care for ARF/RHD. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed/MEDLINE, EMBASE, Web of Science, World Health Organization Global Index Medicus, and EconLit databases to identify original research on economic evaluations of ARF and RHD interventions between January 2002 and December 2021. Variables extracted included bibliometric data, study country income group ( middle-income countries, LMICs), type of economic evaluation, measures of effectiveness, type of interventions, economic outcomes, and the use of decision analysis. Results: Of 3,980 screened articles, 23 were included in the final analysis. Most studies (56.5%, N = 13) took place in LMICs. Primary prevention and care were most commonly studied (52.2%, N = 12), followed by tertiary care (39.1%, N = 9). Cost-effectiveness and cost-utility analyses (65.2%, N = 15) were the most common type of economic evaluation, followed by cost-of-illness studies (34.8%, N = 8). Effectiveness was most commonly measured as quality-adjusted life-years (30.4%, N = 7) and disability-adjusted life-years (17.4%, N = 4). Most studies (78.3%, N = 18) used decision analysis models. Conclusion: The economic burden due to ARF/RHD is large in LMICs, but economic evaluations in LMICs remain limited. ARF/RHD interventions appear consistently but variably effective and cost-effective to prevent and treat ARF/RHD. Increased research, political prioritization, and public health and healthcare funding are needed to address the global burden of ARF/RHD. 111082 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Post-Heart Transplant Dynamic of Cognitive Functioning, the Structure Indicators of Anxiety and Quality of Life in End-Stage Heart Failure Patients LISAKOVA ANASTASIIA1, Maria Simonenko1, Petr Fedotov1, Larisa Vasilieva1, Yulia Sidorovskaya2, Olga Tarasova1, Svetlana Bagramian1, Aelita Berezina1, Maria Bortsova1, Oleg Mamontov1, Yulia Levashkevich1, Elena Demchenko1 (1) Almazov National Medical Research Centre; (2) Saint-Petersburg state university (SPbU) Introduction: Cognitive impairment and difficulties in coping with negative conditions slows down the rehabilitation. The post-transplant quality of life affects rehabilitation and social adaptation. Objective: To evaluate the dynamics of cognitive and psycho-emotional characteristics of patients with end-stage heart failure before and after heart transplantation (HTx) as a prerequisite for optimization of psychological correction during cardiac rehabilitation. Methods: Study included 60 end-stage heart failure patients (from 07.2019 to 06.2021), 30 of them (mean age-46.9 +- 13.3 yo; 57.1% - male) were examined on pre-HTx and during 6 mo after HTx (1st period - 1-3 mo and 2nd - 4-6 mo), others were excluded due to the various reasons (i.e. still awaiting HTx, death during early-term posttransplant follow-up, etc.). For patients' examination we used Short Form-36 (SF-36), Luria Memory Words Test, Simple analogies method (for the cognitive sphere) and Integrative Anxiety Test (A. Bizyuk et al.) - the tests validated in Russia. Statistical analysis was performed using Student's t-tests and repeated measures ANOVA. Results: At the pre-HTx examination the level of long-term memory was lower than at the 3rd mo after HTx, but decreased by the 6th mo (5.5 +- 1.8; 7.8 +- 1.7; 7.3 +- 1.6, p = 0.013 for trends) Social Functioning was decreasing during 6 mo (50.2 -+- 7.6; 41.7 +- 6.1 (3 mo); 38.1 +- 10.9 (6 mo), p = 0.011 for trend). Role-Physical Functioning increased to the 3rd mo and dropped to the 6th mo (18.9 +- 17,4; 47.3 +- 40.5 (3 mo); 39.3 +- 34.9 (6 mo), p = 0.01). Mental Health improved to the 2nd period (73.1 +- 15.8 vs 57.1 +- 14.9 pre-HTx, p = 0.011). Physical Functioning increased to the both periods: 30.0 +- 19.1; 68.6 +- 20.4 (3mo); 69.4 +- 22.3 (6 mo), p = 0.004 for trend. General situational anxiety leveled up to the 3rd mo but decreased to the 6th mo (4.5 +- 1.9; 5.9 +- 2.1; 2.6 +- 2.1, p = 0.013 for trend), whereas asthenic component dropped in both periods (6.1 +- 1.9; 4.1 +- 2.5; 3.4 +- 2.5, p = 0.014), alarming assessment of future decreased to the 3rd mo (6.2 +- 2.4; 4.7 +- 2.8, p = 0.046). There were no statistically significant differences in the Simple analogies method. Conclusion: The results can be used for psychological support within rehabilitation of HTx patients. Situational anxiety increased to the 3rd mo, thus, psychocorrection of psycho-emotional states is crucial in 1-3 mo after HTx. Social functioning was dropping in 6 mo after HTx, so psychological rehabilitation is necessary in the 4-6 months after HTx. 111092 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Clinical and Epidemiological Profile of Patients Hospitalized for Acute Atrial Fibrillation RICARDO MENDES CARNEIRO1, Eric Costa de Almeida1, Bruno Reznik Wajsbrot1, Daniel Xavier de Britto Setta1, Marcelo Luiz da Silva Bandeira1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Roberta Siuffo Schneider1, Claudia Lanzillotti Weksler1, Andre Volschan1, Fernando Oswaldo Dias Rangel1, Ricardo Mourilhe-Rocha1 (1) HOSPITAL PRO-CARDIACO Introduction: Atrial fibrillation (AF) is an increasingly prevalent condition, with an estimate of almost 60 million people worldwide and 2.5% of the Brazilian population, according to data from the ELSA-BRASIL study, which was not exclusively composed by patients hospitalized for AF. Knowing the clinical profile, cardioembolic and hemorrhagic risk allows personalizing the therapeutic approach in different scenarios. Objective: To identify the clinical and epidemiological profile of patients hospitalized with AF in a quaternary hospital. Methods: Retrospective cohort study of 819 hospitalized patients with a confirmed diagnosis of AF, from January 2018 to December 2021. Data were analyzed using the SPSS20 software. Results: 57.6% of the patients were male, with a mean age of 71 +- 14.4 years. They had the following risk profiles: CHADS2 >=2 in 79%; CHA2DS2VASc >=3 in 63.8%; age >65 years in 72.6%, systemic arterial hypertension in 66.4%, heart failure in 12%, diabetes mellitus in 21.7%, stroke or transient ischemic attack in 8.2%, coronary artery bypass graft surgery previous in 8.6%and previous coronary artery disease in 21.6%. The median of CHA2DS2VASc was 3, and the median of HASBLED was 2. There was reversion to sinus rhythm in 68.3% of the cases. Of these, 52.5% underwent electrical cardioversion (EVC), 22.5% chemical cardioversion and 25% had spontaneous reversion. Regarding oral anticoagulants administered during hospitalization, most used apixaban (25.6%) and rivaroxaban (12%) and only 1.1% had contraindications for anticoagulation. Regarding antiarrhythmics used during hospitalization, amiodarone (29.1%) was the most prescribed one and, of the heart rate control medications, beta-blockers (50.2%) were the most important ones. Complication rates were low, with only 3 embolic (0.4%), 10 (1.2%) hemorrhagic, and 7 (0.9%) deaths. Conclusion: Despite being a population of high-risk AF patients with a high mean age and CHA2DS2VASc >=3, only a few complications occurred. CVE was the method of choice for reversion to sinus rhythm and the most used oral anticoagulant was apixaban. The knowledge of this profile can allow the development of specific care plans for this population. 111097 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Predictors of Failure of Reversion to Sinus Rhythm in Patients Admitted with Acute Atrial Fibrillation ERIC COSTA DE ALMEIDA1, Ricardo Mendes Carneiro1, Daniel Xavier de Britto Setta1, Julia Paulo Mourilhe Rocha1, Thiago Matos Barcellos1, Flavia Prado Fialho Santos1, Bruno Reznik Wajsbrot1, Roberta Siuffo Schneider1, Vitor Hugo Mussi Campos1, Andre Volschan1, Fernando Oswaldo Dias Rangel1, Ricardo Mourilhe-Rocha1 (1) HOSPITAL PRO-CARDIACO Introduction: Strategies aimed at reversing atrial fibrillation (AF) to sinus rhythm aim at better symptomatic control and quality of life. Knowing the clinical factors associated with greater success in rhythm reversal remains a challenge. Objective: To assess failure related factors to revert to sinus rhythm in patients with AF. Methods: Retrospective cohort study of 819 patients hospitalized with diagnosis and AF from January 2018 to December 2021. The parameters analyzed were age, BNP, left atrial size, creatinine and left ventricular ejection fraction (LVEF). Data were analyzed by SPSS 20 software. Results: 57.6% of the patients included were male, with a mean age of 71 +- 14.4 years. They had the following risk profiles: CHADS2 >=2 in 79%; CHA2DS2VASc >=3 in 63.8%; age >65 years in 72.6%, systemic arterial hypertension in 66.4%, heart failure in 12%, diabetes mellitus in 21.7%, stroke or transient ischemic attack in 8.2%, coronary artery bypass graft surgery previous in 8.6%, previous coronary artery disease in 21.6%. The CHA2DS2VASc median was 3, and the HASBLED median was 2. There was reversion to sinus rhythm in 68.3% of the cases. From the comparison between patients discharged in sinus rhythm and those who remained in AF, the profile of patients who were unsuccessful in reversal were older (mean 70.23 +- 14.6 vs 73.95 +- 13.83), had higher BNP (median 216 pg/ml vs 515 pg/ml; p < 0.001), higher creatinine (median 1.0 mg/dl vs 1.1 mg/dl; p < 0.023), median LVEF of 64.0% vs 62.0%, p < 0.332; and higher left atrial volumes (median 41 ml/m2 vs 43 ml/m2; p < 0.013) Conclusion: The parameters associated with failure to revert to sinus rhythm were age, BNP, creatinine and left atrial volume. The understanding of this association may allow the elaboration of failure prediction scores in the reversal of patients with AF. 111099 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Tricuspid Valve-in-Valve Implantation in Failed Surgical Bioprosthetic Valves - Pilot Experience FILIPPE BARCELLOS FILIPPINI1, Cauyna Gurgel Moreira1, Tiago Costa Bignoto1, Mauricio Felippi de Sa Marchi1, Gabriel Kanhouche1, Antonio Fernando Diniz Freire1, Pedro Felipe Gomes Nicz1, Renata de Sa Cassar1, Henrique Barbosa Ribeiro1, Alexandre Abizaid1, Santiago Raul Arrieta1, Fabio Sandoli de Brito Jr.1 (1) InCor - Instituto do Coracao do Hospital das Clinicas da FMUSP Aims: Tricuspid bioprosthesis deterioration is a frequent condition and its treatment (Redo tricuspid valve replacement) is complex and associated with high mortality. Percutaneous tricuspid valve-in-valve implantation (TViV) presents as a safe alternative with favorable outcomes. We aim to describe the pilot experience of TViV procedures. Methods and Results: From June 2015 to August 2022, 12 patients were submitted to TViV procedure in one tertiary-care Brazilian hospital. The median age was 30.0 +- 13.1 years old, 50% of patients with previous infective endocarditis and the number of previous cardiac surgery was 3.2 +- 1.5 per patient. The majority of patients had severe heart failure symptoms (NYHA III or IV in 50%) and the congenital disease involved were tetralogy of fallot or Ebstein anomaly in most cases (66.7%). The mean time since last tricuspid valve procedure was 9.5 years, most of the prosthesis were Braile (33%). The principal mechanism of bioprosthetic valve failure (BVF) was regurgitation in 66% and combined prosthesis dysfunction in 75%. Preprocedural echocardiography identified moderate or severe right ventricular systolic dysfunction in 7 (58%), mean tricuspid gradient of 10.4 mmHg and pulmonary arterial systolic pressure of 34 mmHg. The transcatheter heart valve (THV) prosthesis used was either Inovare (Braile) in 10 (83%) or Sapien 3 (Edwards) in 2 (17%), with sizes 24, 26 or 28 mm equally distributed in 9 (75%) of the cases. Balloon pre-dilatation was used in 7 (58%) and post-dilatation of the THV in 2 (17%). Intraprocedural echocardiographic evaluation of mean tricuspid gradient was 3.5 mmHg with no moderate or severe paravalvular leak. Overall technical success was obtained in 11/12 (92%) of the procedures, due to change in access site from jugular vein to transapical approach in one single case. Mean length of stay was 12 +- 5.4 days, with 67% of patients in NYHA I at discharge. No patient died during the median long term follow-up of 29 months, the antithrombotic regimen was vitamin K antagonist in 10 (83%) and late bioprosthesis thrombosis was observed in 1 (8.3%) case during the follow up, in the context of concomitant covid infection. One year echocardiographic evaluation of mean tricuspid gradient was 7.7 +- 2.4 mmHg and 1 case with moderate paravalvular tricuspid leak. Conclusion: The pilot experience of tricuspid valve-in-valve implantation demonstrated safety, effectiveness and marked improvement of symptoms at mid-term follow-up. 111112 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM What's on Your Plate? COVID-19 and Diet MASHAAL IKRAM1, Mashaal Ikram1, Mina Kerolos2, Mingxi Yu3, Kim Allan Williams2, Max Liebo3 (1) University of Chicago (Northshore University Health System); (2) Rush University Medical Center; (3) Loyola University Medical Center Background: Food choices have been identified as the leading cause of mortality in the U.S., underpinning many chronic diseases, including cardiovascular disease, diabetes mellitus and cancers. During the SARS-CoV-2 pandemic, nutrition quality, specifically plant-based and Mediterranean diets, have been found to be highly protective from moderate to severe COVID-19 illness. In addition, these diets have been promoted by the 2019 ACC/AHA Primary Prevention Guidelines to reduce cardiovascular disease, which remains the leading cause of death of physicians. Objective: We sought to identify the nutritional habits of medical students and practitioners in two Chicago area academic medical centers. The primary aim of the study was to correlate dietary habits that could correlate with the symptomatic response and infection rates of both SARS-CoV-2 virus and its vaccine. Methods: Medical students, residents, fellows and faculty from Loyola and Rush University Medical Centers with exposure to SARS-CoV-2 patients, and who had received two doses of vaccinations were asked to complete a web-based survey between September 2021 to February 2022. Participants provided their dietary habits, any history of SARS-CoV-2 infection, and occurrence of symptoms after either of their two COVID-19 vaccinations. Results: Of the 274 respondents, 14% indicated that they had contracted COVID-19 prior to the survey. Only 18.% had moderate or severe symptoms with the vaccine. The dietary habits, however, indicated that 72% were eating an unrestricted diet (omnivore), 15% were categorized as semi-vegetarian (intentionally reducing, but not eliminating, animal products), 5% consumed seafood, eggs and dairy, but no red meat, 4% ate eggs and dairy without seafood, 4% ate seafood without eggs or dairy, and 0.3% ate no animal products (figure). Given the relative paucity of categorical dietary diversity, there was no analyzable correlation between viral or vaccine symptoms and nutritional habits. Conclusions: This data indicates that very few (11%) of the surveyed physicians follow ACC/AHA Prevention nutritional recommendations, which would lower both cardiovascular and COVID-19 morbidity and mortality. 111121 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Cardiac Vagal and Sympathetic Activity in Frail Elderly LEILA DAL POGGETTO MOREIRA1, Tuany Mageste Limongi Zamperlim2, Giulia Micali1, Camila Martins1, Higor Quintas Goncalves1, Thamyres Oliva Bueno1, Pricila Helena de Souza1, Rodrigo Moreno de Oliveira1, Giovanna Dolder1, Luciana Gonzalez Viscardi Auad1, Adriana Sarmento de Oliveira1 (1) Universidade Anhembi Morumbi UAM; (2) Universidade Federal de Juiz de Fora Background: Impairment of cardiac autonomic modulation during the aging process contributes to the development of cardiovascular events, the leading cause of death in the elderly population, and may indicate that the elderly with frailty syndrome have a poor outcome when compared to other elderly. Objectives: To evaluate the cardiac autonomic response to isometric exercise in comparison to baseline and recovery. Methods: After screening, 54 frail elderly (F) and 12 non-frail elderly (NF). Briefly, using Fried's criteria subject frailty was defined using: handgrip strength, walking speed, unintentional weight loss, report of exhaustion and level of physical activity. The Polar V800 was used to record the RR interval, which was later evaluated by the Kubois HRV Standard. The isometric exercise protocol was performed at 30% of the maximum handgrip strength for 3 minutes. Where appropriate, the Student's t-test or the Mann Whitney U test was used to compare differences between two independent groups. Statistical significance was set at p < 0.05. Results: The F group has a greater value in the LFun index that is associated with cardiac sympathetic and parasympathetic activity at baseline than the NF group [F:55.3 +- 9.7 vs NF:48.8 +- 7.4; p < 0.02], greater LF/HF value [F:1.2 (0.9-1.5) vs NF:0,9 (0,7-1,2); p < 0.02] and lower HFun index value that is related to cardiac parasympathetic activity [F:44.6 +- 9.7 vs NF:50.9 +- 7.2; p < 0.03]. In the recovery measure, the NF group presented higher values in HFun (REC:40.4 +- 6.0 vs HAND:50.6 +- 12.98; p < 0.05). Additionally, it was observed that at the handgrip moment, group F presented a higher LFun value (HAND:59.7 +- 10.8 vs BAS:55.3 +- 9.7); p < 0.02] and a lower HFun value (HAND:40.1 +- 10.8 vs BAS: 44.60 +- 9.77; p < 0.02). On the other hand, still in the F group, a low HFms index was noted during handgrip [REC:153.5 (61-339) vs HAND:93.9 (57-197); p = 0.02]. For the NF group, the handgrip measurement had higher LFun (HAND:59.4 +- 6.1 vs BAS:48.8 +- 7.4; p < 0.00) and LF/HF [(HAND: 1.73 (1.37-1.98) vs. BAS: 0.99 (0.77-1.20); p < 0.01] and lower for the HFnu index (HAND:40.4 +- 6.0 vs BAS: 50.9 +- 7.2; p < 0.00). There were differences between groups for the HFun index [F:44.6 +- 9.7 vs NF:50.9 +- 7.2); p < 0.03], and the LF index (F:55.3 +- 9.7 vs NF:48.8 +- 7.4) p < 0.03] that were low and high in the F group, respectively. Conclusion: Sympathetic activity is increased and cardiac parasympathetic activity is reduced in the frail elderly at baseline, implying greater cardiovascular risk. 111429 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of the COVID-19 Pandemic on Hospital Admissions and Out-of-Hospital Mortality by Cardiovascular Diseases in the City of Curitiba DANIELI CRISTINA PIGOZZO1, Edson Lessa2, Jose Rocha Faria Neto2, Ana Caroline Dariva Chula2, Marcia Olandoski2 (1) Hospital Santa Casa de Curitiba; (2) Pontificia Universidade Catolica do Parana Background: Many countries have shown a decrease in the demand for medical care and an increase in out-of-hospital deaths (EH) caused by cardiovascular diseases (CVD) during the COVID-19 pandemic period. Objectives: To analyze possible differences in the temporal trend of EH deaths and hospital admissions for CVD in the city of Curitiba during the period of the COVID-19 pandemic. Methods: Retrospective, observational, time series study. Individuals admitted in Brazil's Unified Health System network in Curitiba with a diagnosis coded by ICDs I20-I24 and I60-I64 were included. The number of admissions was correlated with the number of EH deaths from CVD and with the number of new COVID-19 cases. The period analyzed was from January 2019 to August 2021. The descriptive analysis was made through graphics. Results: There were 289941 new cases of COVID-19, 13446 hospital admissions and 2336 EH deaths due to CVD. There was a decrease in admissions in the early period of the pandemic (4352 versus 3736 March-December 2019 and 2020) at the expense of fewer admissions for AMI (3307 versus 2435), while those for stroke increased (1044 versus 1301). EH deaths increased mainly from unspecific cardiovascular causes (UCVC). From March to December 2020 this increase was 71% (185 versus 318) compared to the same period in 2019. Conclusion: This study suggests that the COVID-19 pandemic had a negative impact on the evolution of cardiovascular diseases, through a transient reduction in the number of hospital admissions and an increase in the number of EH deaths from CVD. These at the expense of higher mortality from UCVC. 111129 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Effect of Methotrexate Carried in a Lipid Nanoparticles on Left Ventricular Remodeling and Infarct Size in Patients with ST-Elevation Myocardial Infarction: A Randomized Clinical Trial ALINE GEHLEN FERRARI1, Raul Cavalcante Maranhao1, Rocio Salsoso1, Vanessa Maria Gomes Taques Fonseca Baldo1, Gabriela Liberato1, Remo Holanda de Mendonca Furtado1, Talia Falcao Dalcoquio1, Luciano Moreira Baracioli1, Aleksandra Tiemi Morikawa1, Cesar Higa Nomura1, Thauany Martins Tavoni1, Jose Carlos Nicolau1 (1) Instituto do Coracao - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (InCor-HCFMUSP) Background: Inflammation is very important in the pathophysiology of ST-elevation acute myocardial infarction (STEMI), with special role in left ventricular (LV) remodeling. Methotrexate (MTX) is a potent anti-inflammatory drug with a potential benefit in the treatment of STEMI. A formulation of MTX incorporated into lipid nanoparticles (LDE), LDE-MTX, tested in rats with induced myocardial infarction, reduced by 50% the infarct size and improved LV function, without observable toxicity. Purpose: To evaluate effects and safety of LDE-MTX treatment on LV remodeling and infarct size in patients with STEMI. Methods: Randomized, double-blinded, placebo-controlled, proof of concept study. Patients were randomized within 4 +- 2 days after STEMI to receive LDE-MTX (40 mg/m2, intravenous) or LDE-placebo weekly for 6 weeks. The efficacy endpoints were change between 90 +- 7 days and baseline, in LV end-diastolic and end-systolic volumes, LV ejection fraction, LV mass and infarct size, measured by cardiac magnetic resonance. The main safety endpoints were serious adverse events and incidence of hematological, renal, and liver dysfunction. Results: Thirty-five patients were randomized (18 to LDE-MTX, 17 to LDE-placebo). Two patients in the LDE-placebo group and one in the LDE-MTX group refused to continue the protocol and were excluded from the final analysis. The main efficacy results are shown in Table 1. There were no significant differences between the groups regarding safety parameters. Conclusions: In patients with STEMI, LDE-MTX resulted in higher reduction in infarct size and lower LV mass loss, despite no differences in LV volumes. No safety issues were observed. These results encourage further clinical studies on this novel Nanomedicine approach for the treatment of patients with STEMI. 111130 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Aethacizinum: Effective and Safe Antiarrhythmic Drug in Patients with Persistent Atrial Fibrillation for Sinus Rhythm Restoration EMMA SOKOLOVA1, Ainars Rudzitis3, Oskars Kalejs2 (1) Riga Stradins University, University of Latvia, Riga East University Hospital, Pauls Stradins Clinical University Hospital; (2) Riga Stradins University, Pauls Stradins Clinical University Hospital; (3) University of Latvia, Pauls Stradins Clinical University Hospital Introduction: The improvement in cardiac inotropic function after restoration of sinus rhythm in patients with persistent atrial fibrillation (AF) is very important. Previous studies shows that antiarrhythmic class Ic medications are decreasing inotropic function of the heart. Objectives: To investigate safety and efficacy parameters of widely used antiarrhythmic Ic class medication in patients with atrial fibrillation. Methods: 70 patients with persistent AF underwent bicycle ergometer stress test, rest ECG, 24-hours Holter monitoring, echocardiography and blood tests within 1 day and 4 weeks (+-7 days) following electrical cardioversion. We gathered also information considering the quality of life. The investigation protocol included testing with the baseline 100 mg/day aethacizinum treatment. Results: We observed increase in bicycle stress test time from a mean 5,42 minutes to 6,05 minutes (p = 0,005). During Holter monitoring in n = 4 patients (5,7%) atrial fibrillation was observed. Echocardiography showed improve of systolic function from a mean 50% to 55% (p = 0,005), no worsening of diastolic function was observed. There was no significant changes in ECG parameters. Conclusions: No proarrhythmic events were observed during the study. Medication was well tolerated, proved to have high antiarrhythmic efficacy and safety in patients with persistent atrial fibrillation, having no negative inotropic effect on myocardium. 111163 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Fragmentation of the QRS Complex and Early Repolarization Pattern and an Mildly Reduced Ejection Fraction MARIA GORDEEVA1, Irina Serdiukova2, Alexander Krasichkov2, Elena Parmon1 (1) Federal State Budgetary Institution "Almazov National Medical Research Centre" of the Ministry of Health of the Russian Federation; (2) Saint Petersburg Electrotechnical University The key investigation for the assessment of the left ventricular ejection fraction (EF) is echocardiography, however, this method is not a screening method, especially in individuals with mildly reduced ejection fraction (mrEF). At the same time, an ECG is performed in almost all patients with suspected cardiovascular disease and as part of a preventive examination. It is known that traditional ECG-pattern associated with a decrease in EF have a low diagnostic value. Recently, new ECG-patterns associated with depolarization abnormality (fragmentation of the QRS complex (fQRS) and early repolarization pattern (ERP)) have been actively studied. The aim of study is investigated ECG-pattern of depolarization abnormalities (fQRS and ERP) in patients with a mrEF. Materials and methods: The study included 148 patients with ischemic and non-ischemic cardiomyopathy. According to the level of EF, patients were divided into three groups: patients with low EF (lEF) (less than 40%): 31 (25 men, mean age 52.0 +/-15.6); patients with mrEF (49%-40%): 29 (23 men, mean age 54.7 +/- 12.4); patients with preserved EF (pEF) (more than 50%): 88 (57 men, mean age 58.2 +/-12.0) - control group. We used the criteria by Das M. et al, 2006 to identify fQRS and the criteria by Macfarlane P.W. et al., 2015 to identify ERP. Results: In the 1st group (lEF), fQRS was registered in 16 (51.6%) patients, in the 2nd group (mrEF) - in 13 (44.8%), in the 3d (pEF) in 2 (13.6%), p < 0.001. ERP in the 1st group (lEF) was registered in 2 (6.5%), in the 2nd group (mrEF) - in 2 (6.9%), in the 3d group (pEF) ERP - in 11 (12.5%), p = 0,5. As a result of the ROC analysis, a relationship was found between fQRS and an intermediate decrease EF (40-49%). Conclusions: The greatest difficulty for the early detection of heart failure is the group of patients with a mrEF. FQRS has shown its predictive value in identifying these patients. This ECG-pattern must be analyzed to assess the risk of heart failure. 111179 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Relationship between CHA2DS2-Vasc Score and P-Wave Indexes and Echocardiographic Parameters in Patients Without Atrial Fibrillation AMANDA VANESSA DEMARCHI1, Luciana Vidal Armaganijan1, Dalmo Antonio Ribeiro Moreira1, Mariane Higa Shinzato1, Kelvin Henrique Vilalva1, Pablo Santos Graffiti1, Rodrigo Augusto de Miranda Bertin1, Murilo Amato David1, Mathias Antonio Haruno de Vilhena1, Guilherme Dagostin de Carvalho1 (1) Instituto Dante Pazzanese de Cardiologia (IDPC) Introduction: The CHA2DS2-VASc score has been used as a predictor of cardiovascular outcomes even in the absence of atrial fibrillation (AF). Several P wave indexes and echocardiographic parameters are associated with a higher risk of developing AF and thromboembolism; however, there are few studies in patients without AF. Objectives: Primary: Evaluate the association between P wave indexes [P wave duration, dispersion and variability, maximum and minimum P wave duration, P wave voltage in lead I, Morris index, PR interval (PRI), P/PRI ratio and P wave peak time] and CHA2DS2-VASc SCORE in patients without AF and valve disease. Secondary: To assess the relation between echocardiographic parameters [left atrium (LA) and left ventricle (LV) size, LV ejection fraction (LVEF), LV mass and LV indexed mass] and CHA2DS2-VASC score in the same population. Methods: A cross-sectional, descriptive and analytical study in which clinical, electrocardiographic and echocardiographic data from 272 patients without AF and valve disease were collected and analyzed. For statistical analysis, the Chi-Square Test, Mann-Whitney U-Test and Spearman Correlation were used with the significance level of 5%. Results: PRI, LA and LV diameter, LV mass and LV indexed mass were positively associated with CHA2DS2-VASc SCORE, while P wave amplitude, P wave voltage in lead I and LVEF were negatively associated to the same score (Table). The presence of the Morris index was related with high CHA2DS2-VASc. Conclusion: The study of the association between P wave indexes, echocardiographic parameters and CHA2DS2-VASc score may be useful in clinical practice to evaluate patients who trend to have a higher cardiovascular risk using clinical parameters and non-invasive methods in patients without AF. 111181 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of Cardiac, Renal and Hepatic Markers in COVID-19 In-Hospital Patients YURI CAVALCANTI ALBUQUERQUE TENORIO1, Claudia Patricia da Silva Gois2, Lamark Melo Silva Moreira2, Stephanny Isabelly Pessoa Neri de Araujo2, Igor Vieira Lima Alexandre2, Priscila Alves da Silva2, Larine Ferreira Lira3, Edecio Galindo de Albuquerque1, Antonio Everaldo Vitoriano de Araujo Filho2, Francisco de Assis Costa2 (1) Hospital Veredas; (2) Centro Universitario Tiradentes; (3) Centro Universitario Cesmac Introduction: Coronavirus disease (Covid-19) is a pandemic disease caused by SARS-CoV-2 virus first described in Wuhan (China) in 2019. This condition causes general inflammation leading to acute respiratory distress syndrome (ARDS) in severe cases, sometimes requiring mechanical ventilation. The aim of this study is to identify the impact of cardiac, renal and hepatic markers in mortality, hospital staying, development of ARDS, and necessity of mechanical ventilation (MV) in Covid-19 patients. Methods: Case-control study in a philanthropic hospital in the Brazilian state of Alagoas, selecting 103 hospitalized patients from 2020 to 2021 aged more than 18 years old and diagnosed with SARS- infection. Results: Descriptive of the population analysed was 60.2% of male, 47.6% had hypertension, 26.2% had diabetes, 4.9% had cardiac heart failure, 34.9% had history of smoke, 19% had history of alcohol consumption and 2.5% had history of cancer. There was a positive risk between acute renal failure and death (OR = 2.97), similarly there was a positive risk of requiring MV (OR = 1.74), but there was no relation to hospital staying (p = .456). There was no relationship between hepatic injury and death (OR = .862) and hospital staying (p = .429). On the other hand, there was association to the necessity of MV (OR = 2.86). Finally, there was a relation between cardiac injury and death (OR 19.3) and MV (OR 1.38), but no relation in hospital staying (p = .801). Discussion and Conclusion: The study concluded that cardiac, renal and hepatic markers are related to severe Covid-19 requiring MV in the population analysed. There was association between renal and cardiac markers to death, but not hepatic markers to death. 111193 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Trends in Early Mortality Rate in Infective Endocarditis ISABELA GALIZZI FAE1, Pedro Henrique Oliveira Murta Pinto MD1, Fernando Crespo Torres2, Sofia Caporalli Barbosa2, Gustavo Brandao de Oliveira MD1, Rhuan Braga Oliveira2, Lucas Bretas de Padua2, Teresa Cristina Abreu Ferrari, MD, PhD1, Maria do Carmo Pereira Nunes, MD, PhD1 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais; (2) Universidade Federal de Minas Gerais Introduction: Infective endocarditis (IE) is a rare disease associated with substantial mortality. In recent decades, the epidemiology of IE has been changing with an increased age of patients and a crescent number of health-care-acquired IE. However, few studies have examined the contemporary outcomes of IE in this growing population at risk of complications. Objective: The present study aimed to describe the incidence of in-hospital mortality over the past 2 decades and to identify the risk factors for early mortality in a cohort of patients with IE admitted to a Brazilian quaternary hospital. Methods: A total of 334 consecutive patients diagnosed with IE based on modified Duke criteria were prospectively included from 2001 to 2021. Data regarding predisposing baseline condition, laboratory findings, etiologic agents, treatment and in-hospital outcomes were analyzed. The primary endpoint was in-hospital death due to any complication related to IE. Results: The median age was 54 years, 60% men. Cardiac device and rheumatic heart disease were the most frequent predisposing conditions. During the treatment, 78% patients presented adverse events, including worsening of heart failure (HF) (34%), embolic events (13%) and the need for cardiac surgery (43%). The overall in-hospital mortality rate was 34.9% with no changing over this time. In multivariable analysis, the characteristics independently associated with death were embolic events, HF development, increasing age and high CRP levels (C statistic of the model 0.84). Conclusion: Despite recent advances, IE continues to be associated with high in-hospital mortality, without changes in the last 2 decades. Early identification of patients who are at high risk of death may offer an opportunity to improve outcomes in IE. 111215 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Epidemiological Profile of Patients Admitted with Acute Myocardial Infarction Secondary to Spontaneous Coronary Artery Dissection ISABELLE MENDES RODRIGUES SALOMAO1, Marye dos Santos Xavier Dias1, Luanna Damasceno Amaral de Sousa1, Alessandra Arnez Pacheco1, Larissa Guerra Cunha de Sousa1, Daniel Xavier de Brito Setta1, Julia Paulo Mourilhe Rocha1, Fernando Oswaldo Dias Rangel1, Ana Amaral Ferreira Dutra1, Louise Freire Luiz1, Claudia Lanzillotti Weksler1, Ricardo Mourilhe-Rocha1 (1) Hospital Pro-Cardiaco Introduction: Spontaneous coronary artery dissection (SCAD) is considered an uncommon cause of acute coronary syndrome (ACS), in which typical chest pain is the main manifestation, being more common in women <=50 years old. It can be triggered by physical or emotional stress, female sex hormones, inflammatory disorders, fibromuscular dysplasia, and connective tissue disease. Objective: To assess the epidemiological profile of patients with acute myocardial infarction (AMI) secondary to SCAD. Methods: This is a retrospective case series study developed at a Quaternary Hospital in the city of Rio de Janeiro. The database and electronic medical records of 1.200 patients with ACS, admitted between July 2013 and February 2022, were analyzed, in which were selected 0,7% diagnosed with SCAD. Results: Of the 9 patients evaluated, all were female, with a median age of 58 years, 67% had arterial hypertension, 78% obesity, 78% anxiety, 44% smokers, 22% diabetes mellitus, 22% previous AMI and 22% with a positive family history for coronary artery disease. Most (78%) had typical chest pain on admission, with 89% Killip I, 78% non-ST segment elevation AMI, 67% with preserved global left ventricle (LV) systolic function. 11% with severe LV dysfunction and 56% with segmental alteration. Median ejection fraction of LV was 59%. All patients underwent coronary angiography (CAT) within 24 hours of admission, with 67% single-vessel involvement and 44% TIMI III. Conservative treatment, with ASA, clopidogrel, high-potency statin, ACEI and bisoprolol was chosen in 78% of the patients. 22% were treated with angioplasty with drug-eluting stent implantation due to unfavorable coronary anatomy. One patient with extensive and severe lesion of the anterior descending artery and another patient with severe lesion of the marginal artery. 33% of patients had pain recurrence and 22% of whom had recent readmissions due to angina. The length of hospital stay was 5 days. There were no in-hospital deaths. Conclusion: SCAD is more prevalent in females and may be associated with stress factors, smoking and obesity. The approach to patients follows the usual ACS protocol, but it must be considered that the dissection can be aggravated by CAT. Conservative treatment is recommended in most low to moderate risk cases. It is important to perform the differential diagnosis of chest pain in order to avoid underdiagnosis of SCAD. 111760 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Admission Bedside Lung Ultrasound Reclassifies SCAI Shock Classification Mortality Risk in Patients with ST-Segment Elevation Myocardial Infarction GUSTAVO NEVES DE ARAUJO2, Gustavo Neves de Araujo1, Fernando Luis Scolari3, Guilherme Pinheiro Machado3, Anderson Donelli Silveira3, Felipe Pereira Lima Marques3, Rafael Beltrame3, Andre Theobald3, Alan Pagnoncelli3, Rodrigo Vugman Wainstein3, Marco Vugman Wainstein3 (1) Imperial Hospital de Caridade; (2) Instituto de Cardiologia de Santa Catarina; (3) Hospital de Clinicas de Porto Alegre Background: The new SCAI Shock Classification encompasses patients with progressive severity from stage A (at risk) to stage E (Extremis), and early identification of stepping stages is essential to scaling therapy. Lung ultrasound (LUS) evaluates pulmonary congestion, which may be present even in the absence of other signs of overt shock. Our aim was to evaluate prognosis in patients with and without lung congestion evaluated by LUS among SCAI Shock stages. Methods: Cohort of STEMI patients treated with primary PCI in a tertiary center. LUS protocol consisted of 8 scanning zones performed at admission. SCAI shock classification was evaluated within 24h of admission. Primary outcome was in-hospital mortality. Results: We included 582 patients with mean age of 61 +- 12 years and 373 (64.1%) male. SCAI shock stage A was present in 361 (62%) patients, while 115 (19.8%) were class B, 44 (7.6%) class C, 58 (10%) class D, and 4 (0.7%) class E. In-hospital mortality in patients with SCAI Shock classification A-E was 1.4%, 14.4%, 48.9%, 63.8% and 50%, respectively. Among SCAI B patients, mortality in mild (0-3 positive sites) and severe congestion pattern (4-8 positive sites) were 8.8% and 22.2%, respectively. Mortality in SCAI C patients without of LUS congestion (14.3%) was similar to patients in SCAI B stage (p = 0.583). Mortality in SCAI D patients without of LUS congestion (50%) was similar to patients in SCAI C stage (p = 0.631). Conclusion: Among STEMI patients at risk for cardiogenishock, LUS reclassifies SCAI Shock Classification regarding mortality prediction. Absence of lung congestion was associated with one-step decrease of mortality rates in SCAI C and D patients. While this must be tested in larger cohorts, LUS should potentially be included in SCAI Classification. 111288 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Myocardial Ischemia Predictors in Patients with Left Bundle Branch Block ANDRE PINHEIRO ZYLBERMAN1, Lara Teles Alencar Duarte1, Allexa Gabriele Teixeira Feitosa1, Claudia Bispo Martins-Santos1, Yasmin Juliany de Souza Figueiredo1, Cleovaldo Ribeiro Ferreira Junior1, Edvaldo Victor Gois Oliveira1, Arthur Leite Lessa1, Octavio Morais Veloso1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe Introduction: The left bundle branch block (LBBB) is a degenerative condition of the cardiac conduction system that is easily diagnosed by an electrocardiogram. Its prevalence ranges from 0.2 to 1.1%, increasing with age. As it is a chronic illness, patients may also develop several associated pathologies that require careful investigation, including coronary disease. As a result, the determination of heart ischemia predictors takes its place as an important evaluation, especially considering the exercise test's diagnostic difficulties in LBBB subjects. Objective: To determine the predictors of heart ischemia in LBBB patients undergoing physical stress. Methods: This is an observational, cross-sectional and analytical study. It was used a dataset of LBBB patients from a private institution, all of which underwent an exercise stress echocardiography. The selection process excludedindividuals with previous coronary events. A total of 15 variables were studied in relation to the test's result, including: sex, age, body mass index, family background, diabetes mellitus, dyslipidemia, hypertension, obesity, smoking, aortic diameter (AO), left atrium diameter (LA), left atrium volume, left ventricular mass index, ejection fraction and diastolic function. Statistical analysis was performed by the chi-square test (X2) and by the student's t-test, both considering p < 0,05 as significant. The software SPSS Statistics version 22.0 was used. Results: From the 252 patients included in the study, 115 (45.63%) were men and 137 (54.37%) were women. Ages ranged from 30 to 92 years old, with a mean of 64.07 (+-10.93). From the results of the echocardiography, two groups can be clearly identified: positive (n = 64; 25.40%) and negative for ischemia (n = 188; 74.60%). Among the qualitative variables, analysis showed that the male sex was the only associated with heart ischemia (p = 0.01) in LBBB patients. However, among the quantitative variables, AO (p = 0.00), LA (p = 0.02) e left ventricular index (p = 0.02) had significant higher means in the 'positive for ischemia' group. Conclusion: Only four of the 15 possible predictors were significant in the present study. Sex was deemed the only important personal factor for the echocardiography's positive result. However, considering heart measurements as possible predictors, LBBB patients with either a larger atrium or aort, or with a greater ventricular mass were more susceptible to ischemia while facing stress. 111299 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Predictors of Cardiorenal Syndrome Type 1 and Mortality in Patients with Acute Heart Failure: A Case-Control Study TARCIO SADRAQUE GOMES AMORAS1, Giovana Salomao Melo2, Joao Simao de Melo Neto2, Christelaine Venzel Zaninotto1, Vitor Bruno Teixeira de Holanda1, Sheila Santos de Oliveira1, Luana da Silva Freitas1, Luana Santos Nunes1 (1) Division of Cardiology, Gaspar Vianna Clinical Hospital Foundation; (2) UPCEURG, Institute of Health Sciences, Federal University of Para Introduction: Currently, one of the most common causes of aggravation in hospitalized patients with heart failure (HF) is the worsening of renal function. Approximately one-third of patients with acute HF may develop acute renal injury (AKI); this condition has recently been termed cardiorenal syndrome type 1 (CRS-1). Objectives: To identify predictors of CRS-1 and mortality in patients with acute HF in the Eastern Amazon. Methodology: This was an observational, case-control study in which descriptive and inferential analyses were performed. We included 183 patients with acute HF aged older than 18 years admitted from January 2017 to May 2021 at a public referral hospital in the department of nephrology and cardiology. Patients were categorized into two groups: G1, patients with SCR-1 (n = 72), and G2, patients without SCR-1 (n = 111). The prevalence of sociodemographic and clinical factors was determined for both the groups, and independent predictors of SCR-1 and mortality were identified using the logistic regression model. All statistical analyses were performed using SPSS Statistics for Windows, version 21.0. Results: Among 183 patients, 72 (39.3%) developed SCR-1 and 33 (16.6%) evolved with dialysis AKI. Prevalence of chronic kidney failure (CRF) (p = 0.003), uncontrolled hypertension (p = 0.005), non-adherence to food/water (p = 0.043), advanced age (p = 0.004) and elevation of systolic BP (p = 0.021) was observed in the group with SCR-1. Among the factors that contributed to the worsening of acute HF, only non-adherence to dietary and water intake guidelines was considered a predictor for the incidence of SCR-1 (p = 0.003; OR = 81.45; 95% CI = 4.38-1513.13). For in-hospital mortality, only AKI dependent on renal replacement therapy was considered a predictor for SCR-1 incidence (p = 0.010; OR = 15.5; 95% CI = 1.93-124.35). Conclusion: Non-adherence to dietary and water intake guidelines was considered a risk factor for SCR-1. As it is a modifiable factor, preventive actions in public health become relevant for minimizing the occurrence of SCR-1. 111335 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Effect of Sacubitril/Valsartan on Central Hemodynamic Parameters in Patients with Chronic Kidney Disease in CHF with Type 2 Diabetes KHOLIKOVA AZIZA OYBEK1, Abdullaev Timur Atanazarovich1, Kholikova Aziza Oybek1, Tsoy Igor Arsenevich1 (1) Republican Specialized Scientific and Practical Medical Center for Cardiology Purpose of the study: Evaluation of the effect of sacubitril/valsartan on central hemodynamic parameters in patients with chronic kidney disease (CKD), chronic heart failure (CHF) and type 2 diabetes. Material and methods: Randomization included 42 patients with CHF FC class II-III according to NYHA, EF less than 40% with concomitant type 2 diabetes and CKD stages 3a-3b, mean age 50.4 +- 16.6 years. Every 3 months, all patients were determined the content of urea, serum creatinine, the content of potassium, sodium, magnesium and calcium in the blood, GFR, protein in the urine and blood pressure. CKD in history occurred in 100% of patients, arterial hypertension 90%, diabetes mellitus 100%. Previously, patients received standard baseline cholesterol therapy. After 3-4 days of observation, patients were switched to sacubitril/valsartan by standard dose titration. The follow-up period was 18 months. Results: Patients included in the observation who used sacubitril/valsartan were divided into 2 groups according to CKD stages: CKD group 1 GFR up to 45 ml/min/1.73 m2, GFR group 2 above 46 ml/min/1.73 m2 Analysis of integral hemodynamic parameters showed the following. The severity of the decrease in SBP, DBP and HR was greater and had statistical power in patients with eGFR <=45 compared with the group of patients with eGFR >46 ml/min/1.73 m2 ( SBP 16.9 +- 6.24 VS 10 +- 3.18 mm Hg, DBP 10.76 +- 3.48 VS 1.72 +- 2.1 mm Hg, HR 10.38 +- 4.02.24 VS 1.151 +- 3.99 bpm), respectively with an average intergroup t = 2.25; P = 0.03. Those. hemodynamic response was the best in the general group with eGFR <=45 and was almost completely determined by patients with type 2 diabetes. DBP - 14 +- 4 (t = 2.298; P = 0.03); HR 8.4 +- 4.48 was significantly higher in the group with eGFR <=45 than in the group with eGFR >46 SBP - 3.34 +- 4.32 (t = 0.701; P = 0.03); DBP - 2.5 +- 2.17 (t = 0.045; P = 0.8), heart rate 6.25 +- 4.47 (t = 1.423; P = 0.105). The content of urea, creatinine in blood serum did not change significantly in both groups (t1 = 0.439408; t2 = 0.220387). Conclusion: In patients with CHF FC II-III according to NYHA, with an EF less than 40% with concomitant type 2 diabetes, therapy with a neprilysin inhibitor/RAAS blockade was not accompanied by a noticeable decrease in hemodynamic parameters in patients with CKD C3a and C3b. 111350 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Hospital Evolution Comparative Analysis of Percutaneous Coronary Interventions in Acute Coronary Syndrome in Patients with and Without COVID-19 Infection THALES CARDOSO WHATELY1, Joao Gabriel Monteiro Junqueira1, Ana Salome Eurico1, Ana Luiza Iannarella Lacerda1, Barbara Bezerra de Almeida1, Karen Sanae Takehara Vieira1, Mayara Bastos Souza1, Constantino Gonzales Salgado1, Joao Addison Pessoa1, Roberto Pozan1, Esmeralci Ferreira1 (1) Hospital Universitario Pedro Ernesto; (2) Universidade do Estado do Rio de Janeiro Introduction: COVID-19 is a predictor of mortality in acute coronary syndrome (ACS). In a university hospital, in patients with ACS treated by percutaneous coronary intervention (PCI), an increase in mortality and in-hospital complications was observed. In view of these observations and because there are no data related to PCIs in COVID-19, we developed this work. Objectives: The main objective was to assess in-hospital mortality in patients with and without COVID-19 infection and ACS undergoing urgent PCI. The secondary objective was to evaluate cause of mortality and the association with clinical presentations, risk factors and angiographic findings. Methods: It's a comparative, retrospective and consecutive study. A total of 598 patients undergoing PCI in ACS were evaluated. Patients were divided into groups: GI with COVID-19 (N = 76) and GII without COVID-19 (N = 522). Results: The mean age was 62 years. The rate of diabetes, obesity, dyslipidemia, smoking, previous coronary artery disease and systemic arterial hypertension (SAH) were similar. SAH was the most frequent factor (GI = 68.8%; GII = 69.2%, p = 0.99). Renal failure and previous coronary artery bypass graft surgery were more prevalent in GI (11.7%, p = 0.005). ST-segment elevation myocardial infartcion (STEMI) was more frequent (GI = 57.1%; GII = 61.5%, p = 0.53), followed by non-STEMI (GI = 35.1%; GII = 25 .1%, p = 0.07) and unstable angina (GI = 6.5%; GII = 13.4%, p = 0.09). We observed a higher frequency of interventions in anterior descending artery (ADA) (GI = 42.9%; GII = 58.8%, p = 0.01), followed by right coronary artery (GI = 13.3%; GII = 34 .9%, p < 0.001) and circumflex artery (GI = 6.5%; GII = 16.9%, p = 0.02). Mortality was higher in GI (GI = 22.3%; GII = 3.6%, p < 0.001) related to severe acute respiratory syndrome (SARS) (GI = 47.0%; GII = 5.3%, p < 0.001). Cardiogenic shock was greater in GII (GI = 41.2%; GII = 78.9%, p < 0.001). Septic shock was similar in the groups (GI = 11.8%; GII = 10.6%, p = 0.9). In multivariate analysis, the presence of COVID, age, renal failure and the involvement of the ADA showed a positive and significant association with in-hospital death. Conclusion: Emergency care and hemodynamic assessment of ACS took on great importance in pandemic. This study proved that presence of COVID-19 was the main predictor of ACS mortality due to SARS and shock. In addition to COVID-19, mortality is related to age, ADA involvement, and renal dysfunction. 111351 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Analysis of Hospital Cardiovascular Mortality in the State of Rio de Janeiro Pre and Per-Pandemic by SARS-COV-2 THALES CARDOSO WHATELY1, Joao Gabriel Monteiro Junqueira1, Luciana Ludwig Nigri1, Claudia da Silva Lunardi1, Ivana Picone Borges Aragao1, Sara Cristina Marques dos Santos1, Ana Salome Eurico1, Esmeralci Ferreira1 (1) Hospital Universitario Pedro Ernesto; (2) Universidade do Estado do Rio de Janeiro Introduction: The hospital scenario in the state of Rio de Janeiro (ERJ) was overloaded before SARS-Cov-2. Associated with the collapse of the pandemic, there was a reduction in demand for medical services, especially in patients with cardiovascular disease (CVD). COVID-19 represents an additional risk to these individuals. Previous studies have shown lower rates of hospitalization and death from CVD, and an increase in the fatality rate in the pandemic. The lack of epidemiological data related to COVID-19 and mortality in the ERJ led to this study. Objective: Analyze hospital CVD mortality in the health regions of the ERJ in the per-pandemic period of COVID-19 in patients of the brazilian unified health system (UHS). Methods: Descriptive, population-based, retrospective epidemiological study, using the hospital information system database of the UHS informatics department. The periods evaluated were divided in pre-pandemic (2018 and 2019) and per-pandemic (2020 and 1st quarter of 2021). Mortality data were obtained from the International Code of Diseases, which took place in the ERJ, divided into: ischemic diseases (G1), heart failure and cardiogenic shock (G2), cardiac arrhythmia (G3) and myocarditis (G4). Hospitalizations decreased in the regions of Baixada Litoranea (21.21%), Center-South (14.50%), Middle Paraiba (20.86%), Metropolitan I (18.37%), Metropolitan II (5.32%), North (19.44%) and Serrana (16.38%), and increased in Ilha Grande Bay (7.02%) and Northwest (1.72%). There was a drop in mortality in the Center-South (5.07%), Middle Paraiba (25.38%), Metropolitan I (18.09%), Metropolitan II (2.40%), North (11.02%) and Serrana (11.75%) and increase in Ilha Grande Bay (11.32%) and Northwest (9.28%). Conclusion: Hospitalizations in the CVD groups were reduced, especially in G2 patients. There was a significant increase in mortality caused by myocarditis, probably related to the virus. The health regions with an increase in hospitalizations and mortality were Ilha Grande Bay and Northwest Rio de Janeiro. 111352 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY New Risk Score for Predicting Postoperative Atrial Fibrillation After Cardiac Surgery JOAO LINS DE ARAUJO NETO1, Joao Lins de Araujo Neto1, Eduardo Arrais Rocha1 (1) Universidade Federal do Ceara Background: Postoperative atrial fibrillation is the most common sustained arrhythmia after cardiac surgery and occurs in approximately 30% of postoperative patients. Because of the large amount of evidence recommending prophylactic treatment and lack of data indicating who should receive such treatment, this study aimed to develop a new predictive score for atrial fibrillation after cardiac surgery. Methods: This retrospective cohort study included 989 adult patients who underwent cardiac surgery, except for heart transplantation and implantation of a ventricular assist device. Patients with previous atrial fibrillation or those using amiodarone were excluded. The analyzed variables were subjected to a univariate analysis of the occurrence of postoperative atrial fibrillation and a multivariate analysis using logistic regression. Results: Statistically significant variables in the multivariate analysis were age >=60 years (P < .001), left atrial enlargement according to echocardiography (P = .025), inotrope use within 24 hours after surgery (P = .002), and the need for reoperation within 24 hours after surgery (P = .016). The score comprises these four variables and has an accuracy of 77% for predicting outcomes. Scores >=3 were related to a 34% risk of postoperative atrial fibrillation. Conclusions: The proposed score represents the disease pathophysiology well and will be useful in clinical practice. 111354 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Cardioprotection by Human Plasma Transfer After Remote Ischemic Preconditioning: Identification of Cardioprotective Humoral Factors Through Omics Techniques ALBERTO BARRETO GRIMALDI1, Gustavo Monnerat1, Dahienne Ferreira de Oliveira1, Fabio C S Nogueira3, Gilberto B Domont3, Helena Cramer Veiga Rey2, Jose Hamilton Matheus Nascimento1, Antonio Carlos Campos de Carvalho1, Leonardo Maciel1 (1) Instituto de Biofisica Carlos Chagas Filho (Federal University of Rio de Janeiro);; (2) Instituto Nacional de Cardiologia (INC/RJ); (3) Instituto de Quimica (Federal University of Rio de Janeiro) Remote ischemic preconditioning (RIPC) provides myocardial resistance to ischemia/reperfusion (I/R) injuries. The protection mechanism by RIPC is suggested to be mediated by humoral factors. However, the identity of these humoral factors remains enigmatic. We aimed to characterize and identify the humoral factors responsible for the cardioprotection induced by RIPC. Human volunteers signed a consent form and answered a health survey. The volunteers were submitted to RIPC protocol (3 cycles of 5 minutes of ischemia alternated with 5 minutes of reperfusion in the arms). The venous blood was collected before (Placebo plasma) and after RIPC (RIPC plasma). The human plasmas were fractionated in different molecular weight ranges and the cardioprotection was evaluated in isolated hearts of rats submitted to 30 minutes of ischemia and 120 minutes of reperfusion in an isolated heart apparatus. Mass spectrometry (MS) was performed in placebo and RIPC plasma. The fraction less than 10kDa from RIPC plasma reduced infarct size in 50% and induced hemodynamic recovery of hearts submitted to I/R compared to control. The fraction less than 10kDa from placebo plasma did not induce protection. Hearts perfused with the fraction greater than 10kDa or total RIPC plasma also had no cardioprotection. MS showed differences in the protein content, including higher content of adenosine and kininogen in quantitative analysis and the presence of 15 putative cardioprotective proteins in qualitative analysis in the RIPC plasma compared with placebo. The cardioprotective humoral factors are in the less than 10kDa fraction of RIPC plasma. Moreover, the cardioprotection by RIPC can be transferred between species. Adenosine, kininogen, and other 15 proteins could be responsible for the RIPC cardioprotection. 111362 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Analysis of ECG Parameters in Patients with Peripartum Cardiomyopathy KHOLIKOVA AZIZA OYBEK1, Xudoyberganov Otabek1, Abdullaev Timur Atanazarovich1, Tsoy Igor Arsenevich1 (1) Republican Specialized Scientific and Practical Medical Center for Cardiology Objective: To study the features of electrocardiographic changes in patients with peripartum cardiomyopathy in comparison with female patients with dilated cardiomyopathy. Material and methods: ECG and HMECG data of 68 women with peripartum cardiomyopathy and 43 patients with dilated cardiomyopathy were examined. The frequency of occurrence of complete bundle branch block (PBBB) was analyzed. QS phenomenon, atrial fibrillation (AF), ventricular extrasystoles according to Lown's gradation (PV), AV bdokady. Results: ECG analysis showed that complete blockade of the left bundle branch block (LBBB) occurred in patients with DCMP in 12 (27.9%) (kh2 = 7.061; p = 0.008) cases, and in group 1 in 6 (8.8%) cases, respectively. Blockade of the right bundle branch of His (RBBB) was detected in 1 (1.4%) (kh2 = 0.638; p = 0.008) patients from group 1 and was not detected in patients of group 2. A permanent form of atrial fibrillation was in 4 (9.3%) patients with DCMP, and in 1 (1.4%) (kh2 = 3.756; p = 0.053) cases in patients with PCMP (kh2 = 3.756; p = 0.053). Absence of R wave growth or QS complex in chest leads in 8 (12.7%) and 5 (11.6%) (kh2 = 0.000; p = 0.983) patients in groups 1 and 2. AV blockade of the 1st degree was recorded in 4 (5.9%) cases in group 1, in patients from group 2 AV blockade of the 1st degree in 14 (32.5%) cases (kh2 = 13.797; p = 0.001). Negative T wave in 24 (35.3%), group 2 DCMP in 8 (18.6%) (kh2 = 3.576; p = 0.059) cases. HMECG found that ventricular arrhythmias of grades 1 and 2 were 60 (88%) in PPCM, and high grades: paired VA - in 25 (36.8%) and 23 (53.4%) cases (kh2 = 3.002; p = 0.084), respectively, in groups 1 and 2; group VA - 11 (16.1%) and 14 (32.5%) (kh2 = 4.051; p = 0.045); unstable forms of VT - 6 (8.8%) and 9 (20.9%) (kh2 = 3.304; p = 0.070). A stable form of VT was recorded in one case in both groups. Conclusion: In DCM, PBLBBB and 1st degree AV block are significantly more common. At the same time, high grade ventricular extrasystoles and a negative T wave in the chest and standard leads are significantly more common in patients with PPCM. 111367 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Clinical and Functional Characteristics of Heart Failure in Females with the Familial Form of Dilated Cardiomyopathy KHOLIKOVA AZIZA OYBEK1, Abdullaev Timur Atanazarovich1, Tsoy Igor Arsenevich1, Mirzarakhimova Saodat Temurovna1, Bekbulatova Regina Shavkatovna1 (1) Republican Specialized Scientific and Practical Medical Center for Cardiology The aim: To study the clinical and functional features at patients with familial form of dilated cardiomyopathy. Material and Methods: We examined 47 females with the familial form of dilated cardiomyopathy compared with the same of idiopathic dilated cardiomyopathy (n = 50). Examination included: ECG Holter monitoring, echocardiography, test 6-minute walk distance (6MWT). Results: Disease duration was on average 9,4 +- 1,4 and 12,4 +- 1,4 months. (p > 0.05). The length of distance traveled during 6MWT was 264,5 +- 17,3 and 198,4 +- 11,4 m (p > 0.05). Patients with familial form of DCM disease has developed in a relatively early age 36,9 +- 1,6 years, which was significantly lower than in the comparison gr (42,4 +- 1,1 years, p < 0.01). It was shown that AV-blockade I degree was observed with the same frequency in the two grps (12.7% and 14.2%, p > 0.05), however, in the gr with the familial form of DCM in 5 (10.6%) were cases of complete atrioventricular block. Among patients with the familial form of DCM, the LBBB met less frequently (14.8% vs. 21.2%), and AF - more often (19.1% vs. 17.5%, both p > 0.05). The analysis of echocardiographic parameters showed that patients with familial DCM had lower values of ESD (5,6 +- 0, 1 and 6,2 +- 0,1 cm, p < 0.01) and EDD (6,9 +- 0,1 cm and 7,4 +- 0,1 cm, p < 0.01) and EF (37,8 +- 1,8 vs 31,1 +- 1,1%; p = 0.03) compared with patients with idiopathic dilated cardiomyopathy. Conclusions: This form of the disease is associated with younger age, the development of complete atrioventricular block and high rates of left ventricular ejection fraction. 111368 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Short Term Outcomes of Intermediate-High Risk Pulmonary Embolism Stratified by Type of Treatment JULIO LEANDRO BOBADILLA1, Cristhian Emmanuel Scatularo1, Melisa Antoniolli1, Ezequiel Lerech1, Ignacio Manuel Cigalini1, Ezequiel Jose Zaidel1 (1) CONAREC, Consejo Argentino de Residentes de Cardiologia Background: Pulmonary embolism (PE) current stratification includes intermediate-risk patients, in which the specific treatment is controversial yet. The aim of this study was to evaluate short term outcomes of intermediate-high risk patients that received different treatment strategies. Methods: We performed an analysis of a multicenter PE registry. Patients with intermediate-high risk (classification of the European Society of Cardiology) were selected, and clinical variables were stratified by type of treatment received (only antocoagulation or reperfusion with systemic trhombolysis, local thrombolysis, thrombus fragmentation-aspiration or surgical thrombectomy). Results: From 684 consecutive acute PE patients from 75 centres, 178 (26%) were classified as intermediate-high risk. Sixteen percent (n = 28) of this cohort received reperfusion treatment, either systemic thrombolysis (89%) or endovascular treatments, while the rest received only anticoagulation. On multivariable analysis, we found that patients receiving reperfusion strategies were younger (57 +- 17 years vs 68 +- 14; p < 0.001) and had more frequent bilateral PE (78% vs 43.7%, respectively; OR 4.72; 95% CI 1.8-12.3; p < 0.001). No significant differences were observed in total bleeding and major bleeding. 30 days absolute mortality was 3.6% in the reperfusion group and 14% in the non-reperfusion group (OR 0.22, 95% CI 0.02-1.76; p = 0.1). Conclusions: Comparing with anticoagulation only, the use of different reperfusion strategies for intermediate-high risk was safe and showed a trend to improved short-term outcomes, highlighting the need to develop a randomized clinical trial for this specific group of PE patients. 111370 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Physical Activity Behavior of Prediabetes and Diabetes Patients Three Months Later of the Participation in an Exercise Intervention Concluded During the COVID-19 Pandemic JOSIANE APARECIDA DE ALMEIDA1, Ana Paula Delgado Bomtempo Batalha2, Isabela Coelho Ponciano1, Mariana Balbi Seixas2, Tiago Pecanha1, Patricia Fernandes Trevizan3, Raquel Rodrigues Britto3, Lilian Pinto da Silva2 (1) Graduate Program in in Rehabilitation Sciences and Physical-Functional Performance Faculty of Physical Therapy, Federal University of Juiz de Fora, Juiz de Fora, Brazil; (2) Graduate Program in Physical Education, Faculty of Physical Education and Sports, Federal University of Juiz de Fora, Juiz de Fora, Brazil; (3) Graduate Program in Rehabilitation Sciences, Federal University of Minas Gerais, Department of Physical Therapy, Belo Horizonte, Brazil Background: The COVID-19 pandemic imposed critical social restrictions that affected people's behaviors and lifestyles as decreased physical activity. At the same time, healthcare systems recommend home-based exercises as a safe and effective alternative to maintain the population's physical activity levels. Therefore, this study aimed to evaluate motives to maintain physically active and adherence to exercise, as recommended, by patients with prediabetes and type 1 (T1D) and type 2 (T2D) diabetes that participated in a structured exercise intervention delivered partially on-site and partially remote. Methods: This is a cross-sectional study including participants of a pilot randomized trial (NCT03914924) who had completed a 12-week exercise intervention. The exercise intervention was switched from an on-site to a remote delivery in March 2020 due to the social restrictions imposed by the COVID-19 pandemic. All pilot randomized trial participants were instructed to maintain at least 150 minutes of vigorous-intensity aerobic physical activity, as measured by the Borg scale, and 2 to 3 sessions/week of resistance exercise. The motives for maintaining physically active were evaluated by the Motives for Physical Activity Measure-Revised scale (MPAM-R), a twenty-six self-administered questionnaire encompassing five motives (enjoyment, competence, appearance, fitness, and social). Exercise adherence, as recommended, was evaluated by the Brazilian Portuguese version of the Exercise Adherence Rating scale (EARS-Br), a six-items self-administered questionnaire containing six items scored from 0 to 24. A score of seventeen is a cutoff point that demarks adequate adherence to the recommended exercise. Results: Fifteen patients (58 +- 11 yrs; 53% female; 13% prediabetes, 27% T1D, 60% T2D) participated in the study. Thirteen participants (87%) reported maintaining physical activity three months after the exercise intervention conclusion. The descending order of median scores obtained in each motive for physical activity was fitness, enjoyment, competence, social, and appearance. The median (interquartile range) of the EARS-Br total score was 17 (13-23), revealing over half, 53% (n = 8), of the participants adhered to physical exercise as recommended at the end of the exercise intervention. Conclusion: Health concerns are the main motive for patients with prediabetes and diabetes to maintain physical activity during the pandemic COVID 19. 111371 Modality: E-Poster Young Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Differences in Echocardiographic and Functional Parameters and Quality of Life between the Levels of Physical Activity in Patients with Chagas Cardiomyopathy: A Cross-Sectional Study WHESLEY TANOR SILVA1, Matheus Ribeiro Avila1, Pedro Henrique Scheidt Figueiredo1, Lucas Frois Fernandes de Oliveira1, Vanessa Amaral Mendonca1, Ana Cristina Rodrigues Lacerda1, Vanessa Pereira Lima1, Henrique Silveira Costa1 (1) Universidade Federal dos Vales do Jequitinhonha e Mucuri UFVJM Introduction: Physical training seems to promote important clinical, functional, echocardiographic and quality of life changes in patients with Chagas cardiomyopathy. Thus, it is important to verify the differences in the parameters mentioned in the different levels of physical activity presented by the patients. Objective: To verify the functional, echocardiographic and quality of life differences in different levels of physical activity in patients with Chagas' heart disease. Methods: Seventy-eight patients with Chagas cardiomyopathy (53 +- 10 years, 55% male, NYHA I-III, LVEF 53 +- 16%) were selected and evaluated by echocardiography, Cardiopulmonary Stress Test and by Minnesota Living with Heart Failure Questionnaire. Patients' physical activity level was assessed by the International Physical Activity Questionnaire (IPAQ), classifying patients as sedentary, insufficiently active, active and very active. Resulted: Insufficiently active Chagas patients (n = 13, 17%) presented younger age (p = 0.019), greater curve of ventilatory carbon dioxide equivalent (VE/VCO2 slope) (p = 0.003) and greater left ventricular diastolic diameter (p = 0.020) in relation to active (n = 38.49%) and younger age (p = 0.023), lower left ventricular ejection fraction (p = 0.017) and greater left ventricular diastolic diameter (p = 0.012) in relation to the very active (n = 27, 34%). There was no difference in quality of life, resting heart rate, blood pressure and VO2peak between the groups. When comparing the active with the very active, there was no difference between any of the variables analyzed. In the total sample, the level of physical activity correlated with the VE/VCO2 slope (r = -0.447; p < 0.001), with age (r = 0.249; p = 0.028), with left ventricular ejection fraction (r = 0.276; p = 0.016) and left ventricular diastolic diameter (r = -0.300; p = 0.009). Conclusion: Insufficiently active chagasic patients had worse values of the main functional and echocardiographic parameters. In addition, the level of physical activity correlated with well-established prognostic markers for this population, however, without influencing the quality of life of patients with Chagas cardiomyopathy. 111372 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Relationship between Cardial Dysfunction and the Level of ST2 Biomarker in Patients with Dilated Cardiomyopathy KHOLIKOVA AZIZA OYBEK1, Abdullaev Timur Atanazarovich1, Gulomov Khumoyun1, Tsoi Igor Arsenevich1, Akhmatov Yashin Ravshanovich1 (1) Republican Specialized Scientific and Practical Medical Center for Cardiology The aim of the study: To assess the relationship between the parameters of cardiac dysfunction according to echocardiography and the level of the ST2 biomarker in patients with dilated cardiomyopathy. Materials and Methods of the trial: The study included 38 patients (28 men and 10 women) with dilated cardiomyopathy, with an average age of 49 years. Depending on the ST2 level at admission, patients were divided into 2 groups: a group with an ST2 level >=35 ng/ml and a group with an ST2 level <35 ng/ml. In addition to the general clinical examination of patients, an echocardiographic assessment of the state of intracardiac hemodynamics was carried out. The ST2 content in blood plasma was determined by the enzyme immunoassay. Results of the study: The 1st group included 20 people with an increased level of expression ST2 >=35 ng/ml, the 2nd one - 18 patients with ST2 expression level <35 ng/ml. The concentration of soluble ST2 isoform in blood serum in the 1st group was 77.3 +- 24.7 ng/ml, and in the 2nd - 20.6 +- 7 ng/ml (p = 0.000). According to the results of a comparative analysis of structural of the LV functional state in participants at the time of inclusion in the study, it was found that in patients from the 1 group LVEF was 29.9 +- 4.3% and was less by 2.2% (p = 0.035) in comparison with patients in the 2group (LVEF = 32.1 +- 10.9%). EDD - 72.8 +- 3 mm in the 1group 67.6 +- 9.5 mm, in contrast to the 2 group .1 +- 4 mm, 57.7 +- 10.8 mm, .6 +- 3.2 mm, 41.5 +- 4.3 mm, .2 +- 6.1 mm, 40 +- 9.2 mm, LVMM - 355.4 +- 118.4 g, 293.3 +- 74 g, respectively, for the 1st and 2nd groups. Analysis of the relationship between the parameters of the structural and functional state of the LV according to echocardiography revealed a weak positive correlation between LVEF (r = 0.193, p < 0.05) with the concentration of sST2, as well as a positive correlation between the concentration of soluble sST2 in serum and the size of the LV cavities ( dimensions (EDD), r = 0.467, p < 0.05; end systolic (ESD), r = 0.376, p < 0.05; LA size r = 0.273, p < 0.05), and LV myocardial mass (r = 0.375, p < 0.05). Conclusion: In patients with dilated cardiomyopathy, an increased level of soluble ST2 isoform correlates the left ventricular function; the presence of an increased ST2 level in patients with dilated cardiomyopathy is a significant marker of a worse course of CHF. 111376 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Safety of Long-Term use of Intra-Aortic Balloon Pump Therapy in Patients with Advanced Heart Failure Undergoing Heart Transplantation VANESSA SANCHES CORCIOLI BELLINI1, Gustavo Andre Boeing Boros1, Claudia Bernoche1, Milena Frota Macatrao Costa1, Silvia Helena Gelas Lage Pasqualucci1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da USP -INCOR-FMUSP Background: Intra-aortic balloon pump (IABP) is a short-term device that is widely used in patients with advanced heart failure (HF) awaiting heart transplantation (HTx). Complications can be more frequent with prolonged use of the support until HTx. Purpose: Evaluate IABP complications in patients with advanced HF awaiting HTx. Methods: We retrospectively analyzed from 2009 to 2020 in a single center intensive care unit, patients with advanced HF who underwent HTx and received IABP therapy pre-transplant. Patients whose IABP was removed before the transplant were excluded. Prolonged use of IABP was considered over 20 days. We considered IABP relevant complications bleeding, induced thrombocytopenia, infection, and leg ischemia. They were classified as mild or severe. Transfusion or removal for blood complications, replacement and removal for infection and leg ischemia were considered severe. Results: We included 195 advanced HF patients with IABP therapy before HTx. Mean time of IABP onset to HTx was 26 +- 23 days and 107 days was the longest used time. The main cardiomyopathy etiology was Chagas Disease, followed by idiopathic. Left ventricle ejection fraction (LVEF) was 24 +- 6% (TABLE 1). Fifty-two patients had IABP complications. The most frequent complications were induced mild thrombocytopenia and severe infection (TABLE 2). Bleeding occurred in 12 patients and leg ischemia in 5. The IABP replacement occurred in 43 patients and the main reason for replacement was infection. Infection was the only complication that correlated with prolonged use (p = 0.0004). No deaths were attributable to IABP complications. Conclusion: IABP is a safe therapy with low complication rates, most of them minor. Except for infection, complications analyzed were independent of IABP duration. 111384 Modality: E-Poster Young Researcher - Non-case Report Category: DIGITAL HEALTH/INNOVATION Virtual Simulation Training as a Tool to Measure the Quality of Medical Knowledge in Hospital Specialized in Cardiology During the COVID-19 Pandemic MIGUEL BARELLA NETO1, Daniel Fontes1, Savio Batista3, Jadhe Maillard4, Heitor Olegario6, Ana Amaral Ferreira Dutra2, Louise Freire Luiz2, Gabriel Paes5 (1) Daktus; (2) Hospital Pro Cardiaco; (3) Universidade Federal do Rio de Janeiro; (4) Universidade Estacio de Sa; (5) Universidade Federal de Sao Paulo; (6) Universidade Federal de Juiz de Fora Introduction: Virtual training is a tool already used for medical education, adaptation of good practices and training of health professionals to new care flows. Goals: In this work, we report a retrospective observational study demonstrating the results of a Virtual Simulation Training (VST) used as a tool to measure medical knowledge, which allowed a focused face-to-face training intervention during the COVID-19 pandemic in a hospital specializing in cardiology. Materials and methods: During the 3-month period, a VST was performed by the COVID-19 team of the hospital specialized in cardiology, with delivery of a pre and post-test form to evaluate the results. The questions on the form were divided into 5 main criteria: A) Appropriate indication of diagnostic tests for COVID-19 and rational use of resources; B) Recognition of signs of severity and adequate follow-up of patients with suspected COVID-19; C) Use of antibiotic therapy and opening of a sepsis protocol in patients with suspected COVID-19; D) Management of oxygen therapy; E) Airway Management; and F) Cardiovascular emergencies concomitant with COVID-19. The answers to these forms were evaluated according to the percentage of correct answers in good (>90%), medium (between 70-90%) and low (<70%) at the end of the training and, after the results, a face-to-face intervention focused on low performance criteria. Results: The results of the post-test criteria showed Criterion C presenting a good result, Criteria A, B, D and F an average result and Criterion E a low result after the test. VST Criterion E (airway management), due to its low result, was selected for a new face-to-face intervention for airway management. The training consisted of training the entire medical team of the hospital in orotracheal intubation (OTI) through dummies, in airway management. After training, when analyzing the number of complications associated with OTI in the period prior to VST, there was an end to complications of airway management in COVID-19 patients. Conclusions: In addition to being an ally in online medical training, the VST can be a possible tool to show medical training deficits in teams, which may result in choices efficient face-to-face training in specialized teams. 111390 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The Prevalence of Cardiometabolic Multimorbidity and Its Associations with All-Cause Mortality and Premature Mortality in China: A Nationally Representative Population-Based Cohort Study WILLIAM YANG ZHAO1, Lili Song2 (1) The George Institute for Global Health, China; (2) The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia Background: Cardiometabolic disease has been a clinical challenge worldwide and a major public health issue. We aim to examine the epidemiology of cardiometabolic multimorbidity and the association of cardiometabolic multimorbidity with all-cause mortality and premature mortality. Methods: This cohort study utilizes data from the China Health and Retirement Longitudinal Study between 2011 and 2018, which includes 9,712 adults aged 45 years and older. Poisson-distributed Generalized Linear Models were conducted to determine the association of cardiometabolic multimorbidity with all-cause mortality and premature mortality. Results: Overall, the prevalence of cardiometabolic multimorbidity was 32.3% among 9,712 Chinese adults, and increased with age. Compared with the group of none and single disease, cardiometabolic multimorbidity was associated with a higher risk of all-cause mortality (Relative risk ratio [RR] = 1.355, 95% CI = 1.140, 1.611) and all-cause death (RR = 1.601, 95% CI = 1.166, 2.199), after adjusting socio-demographic and lifestyle behavioral covariates. Stratified analyses revealed stronger relationships between cardiometabolic multimorbidity and all-cause mortality (RR = 1.486, 95% CI = 1.126, 1.960) as well as premature mortality (RR = 1.994, 95% CI = 1.137, 3.497) among the females compared to the males. The associations of cardiometabolic multimorbidity with all-cause death (RR = 1.784, 95% CI = 1.317, 2.417) and premature death (RR = 1.781, 95% CI = 1.098, 2.890) were only statistically significant in urban residents. Conclusions: Healthcare systems need to shift from single-disease models to new clinical and public health service delivery models to effectively manage cardiovascular and metabolic diseases as well as multimorbidity. 111413 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The COVID-19 Pandemic and its Effects on Systemic Arterial Hypertension Phenotypes in the City of Sao Paulo MONIZZE VICTORIA ROCHA SENTALIN1, Wilson Nadruz Junior1, Andrei C. Sposito1, Fabiana G. A. M. Feitosa2, Audes D. M. Feitosa2, Marco A. Mota-Gomes3, Weimar S. Barroso4, Roberto D. Miranda5, Andrea A. Brandao6, Eduardo C. D. Barbosa7 (1) Universidade Estadual de Campinas - UNICAMP; (2) Universidade Federal de Pernambuco - UFPE; (3) Centro Universitario CESMAC; (4) Universidade Federal de Goias - UFG; (5) Universidade Federal de Sao Paulo - UNIFESP; (6) Universidade Estadual do Rio de Janeiro - UERJ; (7) Hospital Sao Francisco - Santa Casa de Porto Alegre Introduction: Has been hypothesized pandemic of COVID-19 may have led to inadequate control of cardiovascular risk, like arterial hypertension (HT), due to social isolation and changes in lifestyle habits. However, the impact of pandemic on blood pressure (BP) phenotypes derived from office and out-of-office measures (true normotension, AH sustained, AH white apron, AH masked) is still poorly known. Objective: To compare BP phenotypes before and during the pandemic, and their relation to pandemic's severity in patients Sao Paulo city. Methodology: Retrospective study was conducted analyzing clinical characteristics and measures of BP in office and residential measure of BP (RMBP) in 1529 patients who weren't using anti-hypertensive drugs, from TELEMRPA platform between 2017 and September 2021. Obtained information regarding number of cases and deaths from COVID-19 (SIVEP and SIM/SMS-SP) and medium temperature of Sao Paulo's city in same period. Through analysis of multivariate logistic regression - such as adjustment of BMI, age, sex and ambiental temperature - was avaliated relations between SAH phenotypes, pandemic and its number of cases and deaths from COVID-19. Results: There was an increase in sustained HT (28,2% to 42,2%) and decrease in true normotension (44,5% to 31,8%) in individuals evaluated at the pandemic compared to those evaluated before the pandemic. In addition, BMI and age were greater among patients during pandemic (Table). The relation between pandemic and sustained HT persisted (p < 0,001) and the relation between sustained HT and COVID-19 cases (p < 0,001) and deaths (p = 0,015) every two weeks of COVID-19, even after adjustment for confounding factors. Conclusion: There's a relation between BP phenotypes and COVID-19 pandemic and its severity in Sao Paulo. 111422 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Reperfusion Therapies in Patients with Acute Myocardial Infarction with ST-Segment Elevation: A Comparative Study between the Unified Health System and the Private Network JEFERSON DOS SANTOS1, Suelen Maiara dos Santos1, Luiz Fernando Souza Santos1, Anisia Vieira Souza Fontes3, Aline Barreto Hora2, Adrielly Meneses dos Santos2, Beatriz Silva Ferreira Dantas2, Caio Nemuel Nascimento Santos2, Luiz Ricardo Gois Fontes2, Maria Luiza Leal Paranhos de Oliveira2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe; (3) Centro Universitario Uninassau Introduction: During to the acute ST-segment elevation myocardial infarction (STEMI), the occurrence of clinically relevant events is directly proportional to the time of initiation of reperfusion therapy. Objective: To perform a comparative analysis regarding to the reperfusion therapies used in patients treated in the Unified Health System (SUS) and in the private network. Method: Through the ACCEPT registry database, a project to document the care of acute coronary syndrome in Brazil, patients treated at participating hospitals were selected, whose data were collected from admission to discharge. This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: The procedures performed in 1550 patients (Public = 66.4%; Private = 33.6%) with STEMI were evaluated. Coronary angiography was predominant (Public = 89.3%; Private = 94.8%; p < 0.001) and angioplasty (Public = 73.6%; Private = 81.2%; p = 0.001) in both services. Furthermore, the administration of thrombolytics was performed in 21.8% of patients from the SUS and 10% from the private network (p < 0.001). Only 1.8% of the total number of patients underwent coronary artery bypass graft surgery and 16.9% did not undergo any reperfusion therapy. Conclusion: There was a statistically significant difference in the performance of coronary angiography, angioplasty and use of thrombolytics. 111432 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The Prevalence of Cardiometabolic Disease Multimorbidity and its Associations with Functional Disability in China: A Nationally Representative Population-Based Cohort Study WILLIAM YANG ZHAO1, Siqi Zhao3 (1) The George Institute for Global Health, China; (2) The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; (3) Yantaishan Hospital of Yantai, Yantai, Shandong, China; (4) Yantai Sino-French Friendship Hospital, Yantai, Shandong, China Background: Cardiometabolic disease has been a clinical and major public health challenge worldwide. We aim to examine the epidemiology of cardiometabolic multimorbidity and the association of cardiometabolic multimorbidity with the onset of functional disability. Methods: This cohort study utilizes data from the China Health and Retirement Longitudinal Study between 2011 and 2018, which includes 9,016 adults aged 45 years and older. Poisson-distributed Generalized Linear Models were conducted to determine the association of cardiometabolic multimorbidity with the activities of daily living (ADL) limitation and the instrumental activities of daily living (IADL) limitation. Results: The prevalence of cardiometabolic multimorbidity was 31.9% among 9,016 Chinese adults, and increased with age. Compared with the group of none and single disease, cardiometabolic multimorbidity was associated with a higher risk of ADL limitation (Relative risk ratio [RR] = 1.297, 95% CI = 1.160, 1.450) and of ADL limitation (RR = 1.165, 95% CI = 1.054, 1.288), after adjusting socio-demographic and lifestyle behavioral covariates. Stratified analyses revealed stronger relationships between cardiometabolic multimorbidity and the onset of ADL limitation (RR = 1.309, 95% CI = 1.138, 1.505) among the females compared to the males. The association of cardiometabolic multimorbidity with IADL limitation was only statistically significant (RR = 1.473, 95% CI = 1.158, 1.676) in urban residents. Conclusions: Cardiometabolic multimorbidity is associated with the greater onset of functional impairment. The Health system needs to shift from single-disease models to new clinical and healthcare delivery models to effectively manage cardiometabolic multimorbidity. 111460 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Assessment of Cholinergic Enzyme Activity as a Possible Therapy Against Damage from Ischemic Heart Disease JULIA LEAO BATISTA SIMOES1, Julia Leao Batista Simoes1, Margarete Dulce Bagatini1 (1) Universidade Federal da Fronteira Sul Heart failure (I/R) injury is an important cause of myocardial infarction and heart failure after cardiovascular surgery. Among the therapeutic possibilities, the modulation of the cholinergic system has been highlighted as a prevention of cardiac dysfunction after a cardiac event. The central mechanism of the cholinergic system is related to the stimulation of inflammatory agents in the afferent branch of the vagus nerve. From this perspective, the literature suggests that the greater availability of ACh during and after ischemic deficiencies is associated with a preservation of cardiac function. Thus, the present study was designed to investigate the enzymatic activity of cholinesterases in patients with RHI, given the relationship between Ach and protection against heart problems. Seventy patients with IHD from the Hospital of the Federal University of Santa Maria were selected for the study. Ten milliliters of blood were obtained from each patient and used for biochemical determinations. The protocol was approved by the Human Ethics Committee of the Health Sciences Center of the Federal University of Santa Maria. Thus, the present study demonstrated that the enzymatic activity of AchE and BuChE is increased in patients with IHD, directly responsible for the reduction of ACh in the middle and triggering a worsening in the outcome of the disease. 111444 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Association of Potassium Disorders with the Mode of Death in Patients with Chronic Heart Failure IVNA GIRARD CUNHA VIEIRA LIMA1, Ivna Girard Cunha Vieira Lima1, Jairo Tavares Nunes2, Igor Henrique de Oliveira2, Fernanda Ronco4, Edimar Alcides Bocchi2 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (2) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (3) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; (4) Therapeutic Area Leader - CVRM, AstraZeneca, Brazil Background: Previous observational trials suggested a U-shaped association between potassium disorders and clinical outcomes in HF. However, the mechanism and modes of death, as well as the factors influencing this association are not yet fully understood. Aim: Evaluate the association of potassium disorders with all-cause mortality, as well as to describe the association of potassium disorders with the mode of death in patients with coexisting HF. Methods: A retrospective cohort study conducted in a tertiary hospital from January 2013 to December 2020 including 10390 patients. In-hospital deaths were reported by cause and outside of the hospital deaths were considered sudden deaths. Results: Among the causes of in-hospital death HF was reported in 41.7%, cardiogenic shock in 31.2%, and other causes of death in 25.3%. Death outside of the hospital was reported in 12% of patients. The association between serum potassium disorders and mortality was stronger for severe hyperkalemia, adjusted HR (aHR) of 2.06 (1.36-3.12, p < 0.01), and hypokalemia, aHR of 1.93 (1.42-2.63, p < 0.01). Mortality outside of the hospital was more frequent in patients with hyperkalemia (8.7%) in comparison with hypokalemia (4%). Conclusion: Concurrent potassium disorders were associated with mortality in HF. The potassium disorders may have potential to be a new frontier in the management of HF. Out-of-hospital deaths, were more frequently reported in patients with hyperkalemia. 111451 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Multiprofessional Care Protocol for Patients with Heart Failure During the COVID-19 Pandemic EMILY JUSTINIANO1, Leticia Orlandin1, Luisa Mendes Silveira1, Simoni Chiarelli Da Silva Pokorski1 (1) Hospital de Clinicas de Porto Alegre Introduction: During the SARS-CoV-2 pandemic, the population also suffers from the damage associated with the reduction in the number of outpatient visits and elective exams. In this sense, telemedicine was promoted and expanded, and it served as a strategy in the follow-up and control of patients with chronic diseases, such as heart failure (HF). Objectives: To report the experience of a care protocol, including nursing teleconsultation, during the covid-19 pandemic in patients with heart failure. Method: Experience report of descriptive character constructed from the experience of teleconsultations with patients from a university hospital in southern Brazil during the Covid-19 pandemic. Experience report: In HF, multiprofessional programs focused on care transition, patient education, medication regimen simplification and outpatient follow-up are effective in reducing costs and readmissions. However, during the pandemic period, there was need to reduce outpatient care, which caused a greater team distancing of the patient to the care team which may have contributed to HF decompensation. Faced with this challenge, the nursing team implemented teleconsultation for patients with HF. The team composed of nurses and academic students, physiotherapists and dietitians was trained to use a telephone care protocol based on the application of the European scale, validated for use in Brazil, which evaluates self-care - European Heart Failure Self Care Behavior Scale - EHFScBS. The process begins during hospitalization for decompensated HF, where the patient is evaluated for his/her self-care, receives health education by a multidisciplinary cardiology team, establishes bonding; and has post-discharge follow-up by the team through teleconsultations. In the immediate post-discharge period (5th to 7th day) a telephone call is made with the same questions applied during the hospital evaluation and educational guidelines for self-care are resumed. For the patients who were not hospitalized during the pandemic, teleconsultations were also carried out. Conclusions: The team observed that teleconsultation proved to be efficient for the control of adherence to therapies and it also served as an instrument to reconnect the patient to the team. However, it is worth mentioning that the inability of some patients to use electronic devices, as well as the absence of physical examination during the consultation are some of the difficulties encountered in the use of such strategy. 111487 Modality: E-Poster Young Researcher - Non-case Report Category: NUTRITION Abdominal Obesity Among Smokers with Multimorbidities Undergoing Treatment for Smoking Cessation FERNANDA SILVA MOTTA1, Gabriela Godinho Rezende1, Rodrigo Maximo Silveira1, Samuel Barud Massensine1, Rafael Matoso de Oliveira Figueiredo1, Amanda Goncalves Vieira Martins1, Bianca de Fatima Pereira1, Moises de Toledo Vilela1, Paula Gouvea Abrantes1, Marcela Rabelo1, Eliane Ferreira de Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Internship Department, Medical School of the Federal University of Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais, Brazil Introduction: Abdominal obesity represents an important additional risk factor for both the development of chronic non-communicable diseases, cardiovascular diseases, cancer and diabetes. There is evidence in the literature of the association between smoking and abdominal obesity, in which nicotine acts by increasing insulin resistance and, consequently, is related to the deposition of fat in this region. Objectives: To analyze characteristics associated with abdominal obesity in smokers with multimorbidities. Methods: Longitudinal study, from the "Free Tobacco" group, attended between August/2021 to April/2022, referring to treatment groups consecutive sessions for smoking cessation (with mixed intervention, face-to-face and by telemedicine), composed of a multidisciplinary team, including sessions of cognitive behavioral approach, drug treatment and follow-up. Abdominal obesity was defined as waist circumference (WC) >80 cm for women and >94 cm for men. Light smokers, for use <=10 cigarettes/day. Abusive use of alcohol, for Audit-C >=5 points. High risk for Obstructive Sleep Apnea Syndrome (OSAS), Stop-Bang questionnaire >=5 points. Abnormal systolic blood pressure (SBP), >130 mmHg. Results: 36 users were evaluated, referring to 6 intervention groups. When comparing those with abdominal obesity (60% of the sample) with those who did not, it was observed that these users were predominantly male (p > 0.031), light smokers (p > 0.057) and with alcohol abuse (p > 0.002). As for chronic conditions, they had a higher prevalence of obesity (p > 0.001), OSAS (p > 0.049), diabetes mellitus (p > 0.001), previous acute myocardial infarction (p > 0.001) and peripheral vascular disease (p > 0.001). Allied, higher abnormal SBP (p > 0.021) and increased levels of total cholesterol and LDL-cholesterol (p > 0.021 and p > 0.021, respectively). Conclusions: Among users undergoing treatment for smoking cessation, abdominal obesity was a frequent condition, with the majority of men in abusive alcohol use, but light smokers. Comorbidities associated with vascular damage, as well as lack of lipid and blood pressure control, in addition to OSAS, made up the profile of this population. 111488 Modality: E-Poster Young Researcher - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Antithrombotic Treatment Before Transcatheter Aortic Valve Implantation: Features and Clinical Impact CARLOS ROCA GUERRERO1, Carlos Roca-Guerrero1, Joana Brito2, Beatriz Silva2, Pedro Carrilho-Ferreira2, Claudia Jorge2, Pedro Cardoso2, Hugo Corte-Real2, Marcelo Rizzo1, Pedro Canas-Silva2, Fausto Pinto2, Luis Bras-Rosario2 (1) Hospital Universitario Parc Tauli de Sabadell (Barcelona); (2) Hospital Santa Maria de Lisboa - Centro Hospitalar Universitario Lisboa Norte Introduction: Severe aortic stenosis patients frequently suffer other conditions that require antithrombotic treatment. Features regarding different antithrombotic therapy (AT) and their clinical impact on patients admitted for elective transcatheter aortic valve implantation (TAVI) are not well known. Our aim was to describe AT's diversity and explore its clinical impact in patients admitted for TAVI. Methods: We analyzed retrospectively clinical, laboratory, echocardiographic, angiographic, drug therapy and procedure-related variables from 202 consecutive patients with TAVI between January 2019 and October 2021. Results: This cohort had a mean age of 82,3 +- 5,9 years, 56% male, 83% hypertensive, 62% dyslipidemia, 35% diabetic, 20% chronic kidney disease, 32% had coronary artery disease, 20% previous percutaneous coronary intervention (PICP), 38% Atrial Fibrillation, 18% peripheral arterial disease, 12% cerebrovascular disease. 50% of TAVIs were balloon-expandable and 50% self-expandable. The mean follow up was 11 +- 8 months. 128 (63,4%) patients were under any antithrombotic treatment before admision. 44 (21,5%) under single antiplatelet treatment (SAPT), 11 (5%) under double antiplatelet treatment (DAPT), 9 (9%) under SAPT plus oral anticoagulation (OAC), 2 (1%) under DAPT plus OAC; 62 (30,5%) were under isolated OAC (2 of them with warfarin and the rest with direct OAC). 73 patients (36%) were receiving OAC and 84 (41,6%) were under an antithrombotic strategy different than just SAPT. At the univariate analysis receiving OAC, higher mean hemoglobin during hospitalization and previous percutaneous coronary intervention were all statistically associated with survival at the end of follow up; P < 0,05. At the multivariate analysis adjusted by the previous variables, sex, history of coronary artery disease and age, only PICP, and hemoglobin levels were statistically associated with survival at the end of follow up; P < 0,05. Conclusions: In our patient's population, AT before TAVI-related admission was frequent and diverse. Previous PCI and bleeding were the only variables independently-asociated with mortality. These findings emphasize the importance of balancing bleeding and thrombotic risk when treating these patients, even before the TAVI procedure. 111494 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Novel Predictors of Af Recurrence After Catheter Ablation in Patients with Paroxysmal AF MARIANA RIBEIRO SILVA1, Gualter Santos Silva1, Pedro Ribeiro Queiros1, Rafael Teixeira1, Sara Fernandes1, Joao Almeida1, Paulo Fonseca1, Marco Oliveira1, Helena Goncalves1, Alberto Rodrigues1, Joao Primo1, Ricardo Fontes-Carvalho1 (1) Centro Hospitalar de Vila Nova de Gaia/Espinho Introduction: Recurrence of atrial fibrillation (AF) after catheter ablation (CA) is estimated to be between 20% and 45% and the prediction of recurrence AF in patients (pts) with paroxysmal AF undergoing CA remains challenging. Objectives: To determine the clinical and procedural predictors of recurrence AF after CA in pts with paroxysmal AF. Methods: Single-centre retrospective study that included all pts with paroxysmal AF who underwent AF CA between 2017 and 2019. Ablation procedures included radiofrequency and second-generation cryoballoon CA. All pts underwent cardiac computed tomography prior the procedure. AF recurrence was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 seconds (recorded in 12-lead electrocardiogram or Holter) after 90 days of CA. The independent association between clinical and procedural variables and AF recurrence was evaluated with Cox regression analysis. Results: We included 351 pts, 63,5% male and with a mean age of 57,1 +- 11,4 years. CHADSVASC score >=2 points were present in 43,7% of the pts, median duration of AF prior the intervention was 3 years (IQR 1-6) and most pts were treated with some antiarrhythmic drug at the time of CA (56,9%). Overall, median follow-up was 27 months (IQR 19-39). AF recurrence was present in 96 pts (27,4%), on average, 15,2 +- 10,4 months after CA. Univariate logistic regression identified female gender, thyroid disease, left atrium (LA) enlargement (defined as LA indexed volume >34 mL/m2 or LA diameter >38 mm for female or >40 mm for male), coronary calcium score >100, epicardial adipose tissue volume, number of previous electric cardioversions, treatment with antiarrhythmic drugs prior CA and the extent of CA (only pulmonary vein isolation (PVI) or PVI and ablation of other lesions) as predictors of recurrence AF after CA in pts with paroxysmal AF (p < 0,05 for all). Cox regression analysis identified female gender (OR 1,615, 95% CI 1,005-2,597; p = 0,008), LA enlargement (OR 2,084, 95% CI 1,207-3,596; p = 0,008) and coronary calcium score >100 (OR 1,958, 95% CI 1,133-3,385; p = 0,016) as independent predictors of AF recurrence. Conclusions: In our cohort, AF recurrence was significantly higher in pts with LA enlargement, with coronary calcium score >100 and female gender pts. 111499 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY The Impact of Pre-Existing Right Bundle Brunch Block on Short and Mid-Term Outcomes After Transcatheter Aortic Valve Implantation MARIANA RIBEIRO SILVA1, Gualter Santos Silva1, Mariana Brandao1, Claudio Espada Guerreiro1, Marco Oliveira1, Helena Goncalves1, Gustavo Pires Morais1, Bruno Melica1, Lino Santos1, Alberto Rodrigues1, Pedro Braga1, Ricardo Fontes-Carvalho1 (1) Centro Hospitalar de Vila Nova de Gaia/Espinho Introduction: Conduction disturbances after TAVI remains one of the most frequent complications of the procedure. Right bundle brunch block (RBBB) is the strongest risk factor, leading to an increased risk of permanent pacemaker (PM) implantation and is associated with an increased risk of early and late mortality following TAVI. Objectives: To evaluate whether pre-existing RBBB is associated to higher risk of permanent PM implantation and short and mid-term all-cause mortality in patients (pts) undergoing TAVI. Methods: Retrospective study of all pts submitted to TAVI between 2016 and 2018. ECG data before, immediately after the procedure, at day 3 post-TAVI and at discharge were collected, and continuous telemetry monitoring was recorded. We evaluated the rates of temporary and permanent PM implantation during hospital stay and at 1-year follow-up (FUP), ventricular pacing rates in the first visit after permanent PM implantation and all-cause mortality at 30-days, 3 and 6 months and 1-year after TAVI. Results: 220 pts were included, 57,3% female, mean age of 80,7 +- 7,0 years; RBBB prior TAVI was present in 18 pts (8,2%). No significant differences were found regarding baseline characteristics between pts with or without RBBB prior TAVI procedure. Pts with RBBB presented higher baseline QRS duration compared with pts without RBBB (140,0 +- 16,9 ms vs 107,9 +- 26,6 ms; p = 0,002), without differences in QRS duration immediately or at day-3 after TAVI (p > 0,05). High-degree atrioventricular block and complete atrioventricular block immediately after the procedure were more frequent in pts with RBBB (44,4% vs 14,5%, p = 0,004). We found no significant differences in the rates of temporary PM in pts with or without RBBB. Pts with baseline RBBB presented significantly higher rates of permanent PM implantation during hospital stay (55,6% vs 20,0%; p = 0,002) - without differences regarding the timing of PM implantation - and higher rates of PM implantation at 1-year FUP (58,8% vs 21,4%; p = 0,002). The rates of ventricular pacing at the first visit after PM implantation in pts with RBBB was 75,0% (vs 47,2% in pts without RBBB; p = 0,139). No differences were found regarding 30-days, 3 and 6 months and 1-year FUP regarding all-cause mortality, between patients with and without RBBB prior TAVI. Conclusion: Pre-existing RBBB significantly increased the risk of permanent PM implantation but was not associated with a higher risk of mid-term all-cause mortality. 111509 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Biopsychosocial Profile of Female Smokers in the Context of Smoking Cessation Intervention BEATRIZ STEPHAN FARHAT JORGE1, Pedro Drumond Maia1, Rodrigo Maximo Silveira1, Samuel Barud Massensine1, Rafael Matoso de Oliveira Figueiredo1, Amanda Goncalves Vieira Martins1, Bianca de Fatima Pereira1, Fernanda Silva Mota1, Gabriela Godinho Rezende1, Moises de Toledo Vilela1, Eliane Ferreira Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Cardiology Department, Medical School, Federal University of Juiz de Fora - UFJF Introduction: Women exhibit peculiar characteristics that influence the smoking habit. The identification of the female profile is an important tool to be used in the approach to smoking, identifying triggers and factors that prevent cessation or favor relapse. Objectives: To analyze biopsychosocial characteristics among women smokers treated in groups for smoking cessation. Methods: Study with a mixed strategy, cross-sectional and longitudinal follow-up regarding smoking cessation, evaluating smokers of the "Livres do Tabaco" Project, intended for smoking cessation, between 09/2021 and 03/2022. Abdominal obesity was defined as abdominal circumference >80 cm in women and >94 cm in men; neck circumference was abnormal if >40 cm. Normal systolic blood pressure <130 mmHg. Depression, score Patient Health Questionnaire (PHQ-9) >=9 points. Cognitive deficit, Montreal Cognitive Assessment <26 points. Results: Thirty-six patients were evaluated, 66.7% of whom were women, 56.63 +- 10.80 years old. Comparing women to men, it was noted that women had statistically significant associations regarding sedentary lifestyle (p < 0.030), abnormal neck circumference (p < 0.002), abdominal obesity (p < 0.031), arterial hypertension (p < 0.007), arrhythmias (p < 0.022), cancer (p < 0.057), depression (p < 0.052) and greater cognitive deficit (p < 0.001). Regarding the use of other drugs, marijuana (p < 0.004) and crack (p < 0.002) had negative associations for females. Regarding smoking history, women had a higher frequency of triggers in terms of habits (p < 0.027), while dependence (p < 0.001) and stress (p < 0.001) were higher among men. In addition, they also presented higher nicotine dependence (p < 0.007). Regarding adherence to meetings, it was observed that the first (face-to-face) and the second (remote) were the most frequent among women (p < 0.052 and p < 0.012, respectively). It was women who exhibited the lowest prevalence of cessation, both in the 4th week (p < 0.052) and in the 12th week of treatment (p < 0.012). Conclusion: The present study revealed that female smokers showed cardiovascular risk factors and tobacco-dependent comorbidities more frequently than men. In addition, high nicotine dependence and greater trigger related to habits were evidenced. Greater adherence to meetings was not enough to give women the highest rate of smoking cessation. 111519 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Exercise Capacity Following Cardiac Rehabilitation Program After Tavi: What is the Role of Mitral Regurgitation? MARIANA RIBEIRO SILVA1, Eduardo Vilela1, Ana Mosalina Manuel1, Ana Raquel Barbosa1, Joao Almeida1, Ana Tavares1, Daniel Caeiro1, Olga Sousa1, Alberto Rodrigues1, Pedro Braga1, Madalena Teixeira1, Ricardo Fontes-Carvalho1 (1) Centro Hospitalar de Vila Nova de Gaia/Espinho Introduction: Severe aortic stenosis (AS) and mitral regurgitation (MR) often coexist. However, conflicting data reside concerning the impact of MR on outcomes after TAVI. Also, very few data exist regarding the benefits of a cardiac rehabilitation program (CRP) following TAVI in pts with MR. Objectives: To evaluate the effect of a CRP in functional parameters after TAVI, particularly in pts with MR grade >= II. Methods: Retrospective study which included all pts submitted to TAVI between 2014 and 2020 that completed a CRP following the procedure. Cardiopulmonary exercise tests (CPET) were performed after TAVI at baseline (pre-CRP) and post-CRP. We evaluated post-CRP peak oxygen consumption (pVO2), pVO2 at the anaerobic threshold (AT), respiratory exchange ratio (RER), VE/VCO2 and CPET duration. MR grading severity was assessed with transthoracic echocardiography performed after TAVI and was divided into 2 groups (grade < II vs grade >= II). Results: 52 pts were included, 59,6% were male, mean age of 78,6 +- 8,6 years-old. Mean STS risk score was 4,9%. Twenty-seven (51,9%) pts had MR grade >= II. Baseline characteristics were similar between pts with MR grade < II vs MR grade >= II, with the exception of the prevalence of coronary artery disease which was higher in MR grade >= II (p = 0,036). Pts with MR grade < II had higher maximum and median aortic gradients before TAVI (p < 0,05 for all). The mean number of cardiac rehabilitation sessions was 21 +- 7, without differences between both groups. In pts with MR grade >= II, there was an improvement in CPET duration after CRP (HF protocol from 03:57 min to 05:02 min; p = 0,017 and modified Bruce protocol from 06:03 min to 06:41 min; p = 0,049) but without significant changes in pVO2 (14,7 mL/kg/min to 14,9 mL/kg/min; p = 0,990), RER or VEVCO2/VO2 ratio. Patients with MR grade < II significantly improved pVO2 (13,8 mL/kg/min to 14,7 mL/kg/min; p = 0,015), and CPET duration with HF protocol from 05:04 min to 06:23 min; p = 0,006 after CRP. There was also an improvement in VEVCO2/VO2 ratio, although not statically significant. Conclusions: Patients with MR grade < II after TAVI who underwent a CRP significantly improved pVO2 and CPET duration. Although pts with MR grade >= II did not improved pVO2 after a CRP, an improvement in CPET duration may translate into a clinical benefit in these pts. These results highlight the importance of further research and personalization among this potentially higher risk subset of pts. 111521 Modality: E-Poster Young Researcher - Non-case Report Category: DYSLIPIDEMIA Effects of Vitamin D Supplementation in Children with Childhood Obesity: A Systematic Review of Randomized Controlled Trials DANNYELLY HYLNARA DE SOUSA CAVALCANTE MAIA1, Antonia Gabriela de Araujo1, Mariana Roberta Santos de Melo1, Maria Eduarda Oliveira Amorim1, Josianne Alves de Freitas Maia1 (1) Faculdade Nova Esperanca de Mossoro (FACENE/RN) Introduction: The worldwide prevalence of obesity is increasing, both in adults and children. When it occurs during childhood, there is an increased risk of developing cardiovascular disease (CVD) in adulthood. Thus, early interventions become necessary to reduce the risk of morbidity and mortality during adult life. Objectives: This study aims to assess whether vitamin D supplementation is efficient to treat childhood obesity. Methods: The present study is a qualitative systematic review, in which we used the prism method for making, we also emphasize that the guiding question was based on the pico strategy. Two databases were used: PubMed and VHL and the descriptors were: "vitamin D" and "Pediatric Obesity", combined with the Boolean operator "AND". We obtained as an initial result a total of 354 articles, however, after adding filters, we obtained a total of 49 articles, which went on to remove duplicates and read the title together with abstract in pairs, according to the inclusion and exclusion factors.; secondary and primary studies, with the exception of clinical trials, a study sample not compatible with the pediatric age group and studies in which the relationship between vitamin D dose and obesity was not detailed, resulted in a total of 09 articles. The selected articles went on to read the full texts which resulted in a total of 04 articles which had their data extracted. Results: Most studies did not statistically perceive the reduction in BMI or change in body mass in the supplemented group. In all studies, patients in the supplemented group had an increase in the serum concentration of 25OHD. According to Mazzochi and colleagues, the association of DHA with vitamin D supplements could help improve vitamin D status, body composition and metabolic markers. Most articles also highlight that the dose used in studies may have been insufficient to reach concentrations in obese patients, which would act actively to reduce their lipid profile. However, Alves et al. highlight that supplementation with 1,000 IU/day for 90 days reduced serum TC, LDL-c and LDL-c/HDL-c ratio without altering body composition. 111531 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Inspiron Real Life Registry RICARDO CZARNOBAI SOCCOL1, Denise Pellegrini1, Ricardo Lasevitch1, Natalia Lamas Bueno1, Carlos Alberto S Mattos2, Augusto Lima Filho3, Noriaki Takeshita4, Silvio Sergio Pontes5, Leandro Zacarias6, Marcelo Sabedotti7, Pablo Teixeirense Tome8, Paulo Caramori1 (1) Hospital Sao Lucas da PUCRS; (2) Hospital da Cidade de Passo Fundo; (3) Santa Casa de Belo Horizonte; (4) Sociedade Hospitalar Angelina Caron; (5) Hospital Sao Marcos; (6) Santa Casa de Goiania; (7) Hospital Geral de Caxias do Sul; (8) Instituto dos Fornecedores de Cana Aims: The goal of this study was to evaluate the performance of a Sirolimus-eluting coronary stent, composed of a metallic chromium-cobalt platform with thin struts (75 mm), which releases sirolimus towards a bioresorbable polymer applied only to the abluminal surfaces, in a real-world scenario as a post-marketing clinical follow-up evaluation. Methods: This is a prospective, multicenter, single arm registry of patients treated with the stent in 18 participant sites. All patients with lesions in native coronary arteries treated with the coronary stent were included. Exclusion criteria were target lesion located at a saphenous vein or arterial graft, and use of another stent than study stent during the index procedure. The primary endpoint was the rate of MACE (cardiac death, myocardial infarction and target lesion revascularization) at 12 months of clinical follow-up. Secondary endpoints were target lesion revascularization and stent thrombosis rates at 12 and 24 months. Results: Between June 2017 and January 2022, 2506 patients were included (2991 lesions). The mean age was 63 +- 11 years and 64.2% were male. Clinical presentation was acute coronary syndrome in 53.2%, diabetes mellitus was present in 35.5%, previous myocardial infarction in 27.4% and previous percutaneous coronary intervention in 18.2% of patients. Most of procedures were successful (99.9%) with only one failure related to a vessel perforation followed by cardiac tamponade. To date, 1688 patients have completed the one-year follow-up. The incidence of MACE at 1 year was 3.5%. Cardiac death was 2.2% and non-fatal myocardial infarction was 1.3%. Target lesion revascularization was only 1.1%. Definitive stent thrombosis was 0.3%. Conclusion: In this interim report, the 1-year MACE rate, as well as the individual components of this endpoint were excellent and consistent with previous results available for this stent and others 3rd generation drug eluting stent. The result of this study demonstrates the safety and efficacy of this stent in daily clinical practice. 111542 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIORESPIRATORY PHYSIOLOGY/BASIC SCIENCE Cardiovascular Repercussions Associated with Changes in the Respiratory Pattern: A Systematic Review of the Literature and Meta-Analysis OLIVIA FAGUNDES BRUNO1, RODOLFO PASSOS ALMEIDA1, JULIA DA COSTA ANCIAES2, VICTOR EMANUEL FAGUNDES BRUNO3, JOSE JARJURA JORGE JUNIOR1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DE SAO PAULO; (2) UNIVERSIDADE FEDERAL DE ALFENAS; (3) PONTIFICIA UNIVERSIDADE CATOLICA DE MINAS Objectives: To evaluate the repercussions of the respiratory pattern of Obstructive Sleep Apnea Syndrome (OSAS) in relation to the occurrence and prevalence of cardiovascular pathologies. Methodology: Systematic review of articles in the databases: Scielo, PubMed, Lilac's, NHR and Cochrane. The following search terms are used: Cardiovascular Disease, Apnea and OSAS, selected without restrictions for the language of the articles and for the gender of the observed population, excluding works from the population under the age of 18 years. The specified outcomes were: hypertension, resistant hypertension, Incident coronary heart disease, heart failure in men, cardiovascular death in mild or moderate apnea, cardiovascular death in severe apnea. Results: A joint analysis of stratified disease data revealed 95% confidence, a positive and significant relationship between apnea and cardiovascular diseases, with the treatment of these diseases being a variation that reduces this correlation. 111549 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Is Office Blood Pressure Underestimating Reality in Pediatric Obese Population? NATALIA ALBERTIN DOS SANTOS1, Luiza do Nascimento Ghizoni Pereira1, Natalia Albertin dos Santos1, Simone Rolim Fernandes Fontes Pedra1, Carlos Augusto Cardoso Pedra1, Oswaldo Passarelli Junior1, Marcio Goncalves de Sousa1, Fernanda Marciano1, Antonio Gabriele Laurinavicius1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Hypertension (HTN) diagnosis depends on the accuracy and representativeness of blood pressure (BP) obtained by different methods. In pediatric obese patients, office BP can present great variability and does not detect nighttime changes. Ambulatory Blood Pressure Monitoring (ABPM) allows recognition of HTN phenotypes and predicts HTN severity in an earlier and assertive way. Objectives: To compare HTN stages defined by office BP with ABPM, and describe prevalence of masked HTM in pediatric sample from a reference service. Methods: Retrospective cohort of pediatric patients with primary HTN. Patients underwent a detailed clinical history and examination. BP was measured by auscultatory method with technique adequacy. BP was checked at 2 other visits (2 week interval) and the mean BP of these 3 visits was used to classify BP according recommendations. ABPM was performed with pediatric validated device, with a revised report for this analysis, according to guidelines. Mean 24-hours awake and sleep BP and load were considered to identify HTN phenotypes according to 95th percentile for sex, age and height. Diagnosis and stages of HTN based on office BP were compared with ABPM. Patients with sustained HTN had secondary causes discharged after investigation and target organ damage (TOD) was also evaluated. Results: Were included 16 patients with primary HTN, mean age 13 +- 3.3 years, 62% male, 87% obese or overweight (mean weight 89 +- 28.9 kg) and 75% with first degree family history of HTN. Of these, as in Figure 1, masked hypertension was detected in 37.5% (6/16), white coat HTN in 12.5% (2/16), and in 68% of the sample (11/16) ABPM classified HTN at higher stage compared to office BP. Nocturnal HTN was present in 81% (13/16). None patient had TOD and at follow-up, 12 required antihypertensive drugs, with 68% of BP control. Conclusion: For this obese primary hypertensive pediatric sample, ABPM seems to be essential for HTN diagnosis and stratification, evidencing frequent nocturnal changes in BP. Complementary tests to investigate obstructive sleep apnea weren't done but this could be an associated factor. 111552 Modality: E-Poster Young Researcher - Non-case Report Category: PSYCHOLOGY Repercussion of Depression on Smoking Cessation Among Smokers with Multimorbidities PEDRO DRUMOND MAIA1, Beatriz Stephan Farhat Jorge1, Bianca de Fatima Pereira1, Ramon Jose Moreira Silva1, Fernanda Silva Mota1, Gabriela Godinho Rezende1, Moises de Toledo Vilela1, Paula Gouveia Abrantes1, Rafael Matoso de Oliveira Figueiredo1, Maria Fernanda Monteiro Lamas1, Eliane Ferreira Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Cardiology Department, Medical School, Federal University of Juiz de Fora, Juiz de Fora - Minas Gerais. Introduction: Smoking is a serious public health problem. Among the several factors that hinder smoking cessation and the maintenance of abstinence, there is the high rate of psychiatric comorbidities, such as depression. Mood disorders are important factors to be considered in the evaluation of smokers, aiming at a better approach to the habit and a greater reduction in it. Objectives: To evaluate the impact of depression on biopsychosocial characteristics among smokers with multimorbidities in the smoking cessation process. Methods: Observational cross-sectional study evaluating medical charts of a public service for smoking cessation ("Livres do Tabaco" Project), between 09/2021 and 03/2022. Depression defined by the score Patient Health Questionnaire (PHQ-9) >=9 points. Cognitive deficit evaluated by the Montreal Cognitive Assessment <26 points. Abdominal obesity was defined as abdominal circumference >80 cm in women and >94 cm in men. Normal systolic blood pressure (SBP) <130 mmHg. Results: Thirty-six patients were evaluated, aged 56.63 +- 10.80 years, and depression was present in 55.9%. Comparing smokers with and without depressive symptoms, it was observed that those with depression had statistically significant associations regarding obesity (p = 0.007); arterial hypertension (p = 0.035) and uncontrolled blood pressure (p < 0.035); greater cognitive deficit (p = 0.022); COVID-19 infection (p < 0.003). In addition, the occurrence of cardiovascular events also had a positive association in these patients: acute myocardial infarction (p = 0.002); heart failure (p < 0.001); peripheral vascular accident (p < 001); greater hospitalization secondary to COVID-19 (p < 0.001). Regarding smoking history, those with depression had a higher frequency of triggers for stress (p < 0001). Regarding motivation, depressed patients had lower rates (p < 0.056), as well as adherence to meetings and smoking cessation in the 12th week of treatment (p < 0.022 and p < 0.001, respectively). Conclusion: Smokers with depression showed significantly more frequent cardiovascular outcomes. Low motivation reflected in lower adherence to cognitive-behavioral approach meetings and smoking cessation. The association between smoking and depression reveals the need for a multidisciplinary approach to the habit to develop more effective interventions, and to remember that depression is also a chronic disease that should be tracked and treated simultaneously to the process for the success of smoking cessation. 111562 Modality: E-Poster Young Researcher - Non-case Report Category: PERIOPERATIVE EVALUATION Perioperative Profile of Cardiac Biomarkers in Renal Transplant Recipients RODRIGO PINHEIRO AMANTEA1, Virgilio Olsen2, Laura Hastenteufel1, Julia Bueno1, Santiago Tobar1, Livia Goldraich1, Roberto C. Manfro1, Flavia K. Borges3, Nadine Clausell1 (1) Hospital de Clinicas de Porto Alegre (HCPA); (2) Santa Casa de Misericordia de Porto Alegre; (3) Faculty of Health Sciences, McMaster University Introduction: Cardiovascular risk assessment is important among renal transplant recipients. Biomarkers, such as cardiac troponin and BNP, have been used as adjunctive tools in cardiovascular risk stratification in non cardiac surgeries, but their use in the context of kidney transplantation is not well studied. Objectives: To describe the perioperative profile of cardiac biomarkers in kidney transplant recipients and its association with delayed graft function (DGF). Methods: Prospective cohort study including deceased donor kidney transplant recipients between September 2018 and March 2020 at Hospital de Clinicas de Porto Alegre. We evaluated BNP at hospital admission and 24 hours after kidney transplantation. High-sensitivity cardiac troponin (hs-cTn) was evaluated at admission, 24 and 48 hours after kidney transplantation. Only patients who presented with no major adverse cardiovascular events (MACE) during the first month of follow-up were included in the analysis. Results: We prospectively included 102 patients, of which 52.9% were male, 82.4% were hypertensive and 19.6% had diabetes mellitus. Admission's BNP median value was 225 pg/ml (IQR 98.6-626 pg/ml), and 24 hours after transplantation was 288 pg/ml (IQR 180-597 pg/ml). Admission's Hs-cTn above the 99th percentile was observed in 35.3% of patients, and was associated with age at transplantation (OR 1.099/CI 1.043-1.173) and male sex (OR 4.667/CI 1.644-14.838). Hs-cTn's median change from admission to 24 hours after transplantation was -13.5% (IQR -32-9%) and from 24 hours to 48 hours after transplantation was -1.2% (IQR -17-5%). After transplantation, 52% of the patients presented with DGF, which was associated with concomitant preoperative cardiac troponin above the 99th percentile and BNP above 100 pg/ml (OR 3.989/CI 1.217-15.765). Conclusions: Baseline cardiac troponin and BNP are elevated in a large proportion of kidney transplant recipients. While BNP has an ascending trend after renal transplantation, troponin tends to decrease following surgery. Both biomarkers might be predictive of non-cardiac endpoints such as DGF. 111640 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Saving Hearts Saving Brains, a Protocol for Parental Guidance and Early Intervention in Infants with Congenital Heart Disease: A Randomized Clinical Trial MARIANE LOPES DA SILVA1, Debora Gomes da Rocha2, Nathalia Bottega Banaletti2, Fernanda Lucchese-Lobato2 (1) institute of Cardiology, University Foundation of Porto Alegre; (2) Hospital da Crianca Santo Antonio, Irmandade Santa Casa de Misericordia Children with congenital heart disease (CHD) are exposed to multiple sources of risk for delayed neurodevelopment. Early intervention (EI) studies show positive results in preventing delays. To evaluate the effectiveness of a home-based parent-mediated EI protocol, on the neurodevelopment of children with CHD, in a 6-9-month cohort. Methods: A single-blind randomized controlled trial of a parent-mediated early intervention for infants with CHD. The 6-week cost-effective protocol of activities for early home stimulation was performed by the parents with the support of a specialist. The protocol was remotely guided by a combination of booklet/toy kit/videos, and WhatsApp check-ins. The Bayley-III was used to assess developmental outcomes. Results: Twenty dyads participated in the final evaluation, 10 in the intervention group (IG), and 10 in the control group (CG), with a mean age in months of 6 +- 2, in both groups. Both had greater female participation (58%). The IG performed better than the CG, at T2, in four of the five developmental domains: cognitive (p < 0.05), receptive language (p < 0.001), expressive language (p < 0.05), and fine motor (p < 0.05). The gross motor subscale was not significantly different between IG and CG at T2 (p = 0.58). The CG group did not differ in scores at T1 and T2 in all domains: Cog, Rec lang, exp lang, fine motor, and gross motor (p = 0.9, p = 0.7, p = 0.3, p = 0.3, p = 0.9, p = 0.6, respectively). The IG significantly differed between T1 and T2 scores for four domains: Cognitive, Rec. Lang., Exp. lang. (p < 0.001), and fine motor (p < 0.05). Gross motor performance in the IG did not differ significantly between T1 and T2 scores (p = 0.1). Conclusion: The intervention was effective in improving the developmental scores of the IG in four out of five areas of development at T2. This study showed that a low-cost remote parent-mediated program can be successful in reducing the risks of significant delays in child development associated with CHD, which can also promote long-term academic and professional success in this population. Trial registry: Protocol registered at register.clinicaltrials.gov: NCT04152330. 111602 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Effect of Repeatedly Applied Cold-Water Immersion on Subclinical Atherosclerosis, Inflammation, Fat Accumulation, and Lipid Profile Parameters of Volunteers STEFAN TOTH1 (1) SLOVACRIN, Slovak Clinical Research Infrastructure Network, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia Introduction: Short-time cold-water immersion (CWI) is associated with significant acute cardiovascular, metabolic, and endocrinological responses. There is, however, no available study following the long-term effect of repeated CWI on atherogenesis, lipid parameters, and fat distribution. This study aimed to explore the suggested protective effect. Investigations and methods: 35 healthy volunteers were followed during the 5-month CWI exposition under standard conditions (three times per week 7-10 min). Neoprene equipment was not allowed; volunteers with followed weight or muscle mass changes over 5% were excluded. Equivalent sham control (N = 30) was included. In the beginning and at the end of the study, blood collection and clinical examinations were made. Lipid and non-lipid parameters, including PCSK9 and hsCRP levels, were quantified. Vascular changes were detected by carotid ultrasound (cIMT) and by echo-tracking for detection of arterial stiffness parameters (PWV; AI; Beta). Liver steatosis quantification was based on the calculation of hepatorenal index (HRI), fat distribution was measured by the quantification of subcutaneous and visceral fat thickness changes. Results: 28 volunteers have completed the given protocol. Significant decrease of cIMT (p = 0.0001); AI (p = 0.0002); Beta (p = 0.0001) and PWV (p = 0.0001) was detected after the long-term repeated CWI. In comparison with the entry values, a significant decrease of hsCRP (p = 0.01) and PCSK9 (p = 0.01) was observed. Liver fat accumulation decreased by an average of 11% in comparison with the entry values (HRI p < 0.001). A significant decrease in LDL; TC; TG and VLDL was followed as well. Conclusion: We suggest a possible beneficial effect of repeated-CWI on atherogenesis, liver fat accumulation, lipid, and non-lipid parameters. 111636 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIO-ONCOLOGY Treatment of Malignant Neoplasms of the Heart, Mediastinum and Pleura in Brazil between 2013-2020 ANA FLAVIA OLIVEIRA DE SOUZA1, Afonso Moraes Melo Junior2, Davi Gabriel Barbosa3, Daniel Oliveira da Costa4, Joao Lucas Watrin Braga5, Juliana Ayumi Azevedo Kurosawa6, Lucas Guimaraes Junqueira7, Paola Bitar de Mesquita Abinader8, Rafaela Oliveira Cardoso9, Rafael Silva Lemos10, Wanda Maria de Franca Pires11, Luis Eduardo Werneck de Carvalho12 (1) Centro Universitario do Estado do Para (CESUPA); (2) Centro Universitario do Estado do Para (CESUPA); (3) Universidade Estadual do Para (UEPA); (4) Universidade Estadual do Para (UEPA); (5) Centro Universitario do Estado do Para (CESUPA); (6) Centro Universitario do Estado do Para (CESUPA); (7) Universidade Estadual do Para (UEPA); (8) Centro Universitario do Estado do Para (CESUPA); (9) Centro Universitario do Estado do Para (CESUPA); (10) Universidade Estadual do Para (UEPA); (11) Universidade Federal do Para (UFPA); (12) Oncologica do Brasil Introduction: Intracardiac tumours can be divided into intramural thrombus, primary cardiac neoplasms and metastatic tumours. The management of these pathologies is generally determined by obtaining the tissue pathology, the type of tumour and its degree of involvement. Among the types of treatment, chemotherapy is the main strategy, as well as radiotherapy, immunotherapy and surgery. These neoplasms, when untreated, present a poor prognosis, which highlights the need for epidemiological studies that highlight the therapeutic modalities available today. Objectives: To establish an overview of the treatment of malignant neoplasms of the heart, mediastinum and pleura in Brazil, between 2013 and 2020. Methodology: This is a descriptive, quantitative and retrospective study, whose data came from the DATASUS database. The data were analysed according to the division by federative units and the variables used were the therapeutic modality, cancer staging, year of treatment, age group, gender and total number of cases per year in the selected period. Results: When evaluating the treatment of these neoplasms in Brazil in the period 2013 to 2020, it was observed the prevalence of treatment lasting up to 30 days (82.2%), with the main therapeutic modality being surgery (66.4%), followed by chemotherapy (20.2%), and radiotherapy (13.2%). Among the cases analysed for treatment, staging 3 prevailed (32.7%), followed by 4 (31.4%), and the year 2019 (29.5%) was the one in which the beginning of treatment was recorded the most. Regarding the age range, the ages 55 to 59 years represented 11.3% of cases, followed by 60 to 64 years with 10.9% and the predominance in the male gender (50.9%). Conclusion: It is observed that primary malignant neoplasms of the heart have a poor prognosis and are submitted to palliative treatment, while in metastatic heart tumours the therapy depends on the tumour of origin. Moreover, there is a slight predominance among males and between the ages of 55 and 64 years. Moreover, the TNM stages 3 and 4 were the most prevalent, as well as surgical and chemotherapeutic therapy. Therefore, it is evident the need for continuous scientific and technological advances employed both in early diagnosis and in therapeutic modalities in order to provide a positive prognosis for these patients. 111635 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Diastolic Dysfunction and Myocardial Ischemia in Chronic Coronary Syndrome EDVALDO VICTOR GOIS OLIVEIRA1, Enaldo Vieira de Melo1, Claudia Bispo Martins Santos1, Lara Teles Alencar Duarte1, Antonio Carlos Sobral Sousa1, Eduardo Jose Pereira Ferreira1, Allexa Gabriele Teixeira Feitosa1, Cleovaldo Ribeiro Ferreira Junior1, Irlaneide da Silva Tavares1, Jose Icaro Nunes Cruz1, Gabriela de Oliveira Salazar1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe Introduction: Left ventricular (LV) diastolic dysfunction is one of the important factors for survival and long-term prognosis in patients with Chronic Coronary Syndrome (CCS). However, the connection between diastolic dysfunction during exertion, Chronic Coronary Syndrome, Myocardial Ischemia (MI) and the profile of increased cardiovascular risk has not been demonstrated over the years. Therefore, there is a need to predict the factors that can aggravate this connection, in order to enable the creation of secondary prevention strategies and decrease the occurrence of unfavorable outcomes. Objectives: To evaluate LV diastolic function and factors associated with the presence of Myocardial Ischemia (MI) in patients with Chronic Coronary Syndrome (CCS). Methodology: A cross-sectional study between January 2000 and January 2022 with individuals with CCS who underwent Physical Stress Echocardiography (FES) in a cardiology referral service. A total of 2000 patients (62 +- 19 years) were categorized according to the presence or absence of MI. Statistical analysis included the chi-square test and t 's Student using SPSS Statistics version 22.0. Results: We found 937 (46.9%) patients without MI and 1059 (53.0%) with MI - of the latter, 22.3%, 60.7% and 17.1% had induced ischemia, fixed ischemia and ischemia fixed and induced, respectively. There was no association between MI and diabetes mellitus, obesity, physical inactivity (p > 0.05). Myocardial ischemia was associated with: hypertension (77.9% vs. 69.8%), dyslipidemia (77.7% vs. 67.9%), positive family history of coronary heart disease (74.1% vs. 63.8%) and previous myocardial infarction (51.8% vs. 22.3%) - p < 0.001. MI was associated with diastolic dysfunction (p < 0.001): most patients with normal diastolic function belonged to the group without MI (17.6% vs. 6.5%, p < 0.00001), the impaired relaxation was not significant between groups (p = 0.4839), pseudonormal function was more prevalent among patients with MI (28.9% vs. 20.9%; p = 0.0002), as was the pattern restrictive (1.8% vs. 0.1%; p = 0.0007). Left ventricular ejection fraction did not differ between the groups with and without MI (p > 0.05). Conclusion: Arterial hypertension, dyslipidemia, family history and previous myocardial infarction have been shown to be predictors of myocardial ischemia. On the other hand, LV diastolic dysfunction was more prevalent in patients with myocardial ischemia. 112114 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Retrospective Cohort Study Comparing the Incidence of Thromboembolic Events in the Pre-Pandemic and Pandemic Period in a Quaternary Hospital in Rio De Janeiro ANA CAROLINA PEDROSO 1, Andrea Ferreira Haddad1, Lara Camporez Menezes Trindade1, Antonio Vitor Martins Amaral1, Priscila Oliveira Diaz1, Bernardo Cleto Teles e Silva1, Joao Felipe Tamiozzo Reis1, Thaisa Rodrigues Garcia1, Alessandra godomiczer1, Flavia de Moraes Pedro Moises1, Monica Amorim de Oliveira1, Luiz Fernando Simvoulidis1 (1) Unimed Rio Hospital Venous thromboembolism (VTE) is the most common preventable cause of death in hospitalized patients. Hospitalization increases the risk of VTE by 8x, generating important clinical consequences such as deep vein thrombosis (DVT) and pulmonary embolism (PE) that can leave severe sequelae and even being the main cause of death that can be prevented in hospitalized patients. Covid19 is associated with a concomitant prothrombotic state, increasing risk of VTE This is a retrospective cohort that evaluated clinical and surgical patients admitted for at least 48 hours at a private quaternary hospital, where we compared data on thromboembolic events in the pre-pandemic period, from January 1, 2018 to November 30, 2019 with patients hospitalized in the period pandemic from January 1, 2020 to March 14, 2021. All patients were evaluated according to risk stratification for VTE by the physician and prophylaxis was instituted according to the risk found, classified as low, moderate and high risk. Patients with COVID19 were classified as high risk. Patients admitted with DVT and/or PE, arterial thrombosis events and those in palliative care were excluded from the analysis. The events of DVT (distal and proximal), device thrombosis (PICC and AVP) and PE were recorded and all results were confirmed with imaging exams through the EcoDoppler study. Results: In the historical cohort Jan 18 to Nov 19, 114 VTE events were reported in a universe of 81,445 patients, corresponding to 0.14% of hospitalizations in this period. Of these, DVT corresponded to 81.5%, PE 15% and 3.5% central venous catheter thrombosis. There were 23 deaths during hospitalization, corresponding to 23.96% of patients who presented VTE during this period. These events account for 0.03% of in-hospital mortality. In the period from January 1, 2020 to March 14, 2021, 126 events occurred among hospitalized patient ina a universe de 15,000 patients. Of these, 120 (95.2%) were due to DVT and 06 (4.8%) to PE, causing 48 deaths, which corresponds to 38.1% of patients who presented VTE within the in-hospital mortality. VTE is a frequent condition in hospitalized patients and is related to longer hospital stay and in-hospital mortality. It is the most common preventable cause of death in hospitalized patients. We have to consider that SARS-COV2, COVID-19 disease, has been associated with a concomitant prothrombotic state and an increased risk for VTE frequency, therefore, an increase in mortality. 111653 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Robotically Navigated Transseptal Puncture System for Left Atrial Catheter Ablation: Pilot Real-Time Virtual Simulation Data AYA MUTAZ ZEIDAN1, Aya Mutaz Zeidan1, Yangyang Dai1, Zhouyang Xu1, Jonathan Behar1, Steven Williams1, Richard Housden1, Aruna Arujuna1, Kawal Rhode1 (1) King's College London KCL Robotically assisted catheter ablation procedures have been shown to be safe, effective and confer both better catheter stability and tissue contact. Despite promising results from robotic cardiac CA systems, all systems require manual navigation for the transseptal puncture access, thus motivating the need to develop a fully robotic TP system. This would potentially improve patient safety, further reduce radiation dose to cardiologists, and pave the way to more complete robotic solutions for CA. The research aim is to present a preliminary design and prototype for a robotic TP system, and demonstrate real-time operation via simulation. By employing computer-aided design (Fusion360, Autodesk, USA) and additive manufacturing methods (Ender 3, Creality, China), a first prototype for a robotic TP system has been designed to achieve the cooperation principle of the transseptal needle and dilator sheath. The prototype implements four degrees-of-freedom to accomplish translation and rotation of the needle and sheath, individually. Safety features include speed and position constraints. The open-source Robot Operating System (ROS 2, Open Source Robotics Foundation, USA) was used for the control architecture. Additionally, ros2_control was used to employ Forward Command Controller for efficient and reliable actuator control. We demonstrated constant positional relationship between the virtual dilator-sheath and the BRK-1 needle, achieved within the ROS 2 graphical interface. In coupling the needle and sheath, the realised system was able to successfully drive to a maximum length of 144.5 mm, with an positioning accuracy of 0.10 mm. The deterministic performance of the system and its real-time functionality exemplified the benefits of leveraging ROS 2. Movement commands were executed within the order of a few microseconds, providing real-time, low-latency operation. This research confirms proof-of-concept for a first prototype real-time control of a Robotic TP system implemented based on the ROS 2 framework. Our next step is to develop a joystick interface and evaluate the system by using an anthropomorphic cardiac phantom. 111655 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Functional Cardiorenal Benefits Induced by Concurrent Exercise Training and Hydrochlorothiazide Treatment in an Experimental Model of Hypertension and Menopause PIETRA PETRICA NEVES1, Maycon Junior Ferreira2, Tania Plens Shecaira2, Michel Pablo dos Santos Ferreira Silva1, Debora Conte Kimura2, Maria Claudia Irigoyen3, Guiomar Nascimento Gomes2, Katia De Angelis1 (1) Nove de Julho University (UNINOVE), Sao Paulo, Brazil; (2) Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; (3) Heart Institute (InCor), University of Sao Paulo (USP), Sao Paulo, Brazil Cardiovascular diseases are currently the main causes of mortality and morbidity worldwide. Systemic arterial hypertension(SAH)is one of the main risk factors for cardiovascular outcome. Pharmacotherapy associated with exercise training is clinically recommended for the control of blood pressure(BP)to manage SAH. To investigate the effects of concurrent exercise training(CET)and pharmacological treatment with hydrochlorothiazide on hemodynamic and renal parameters in an experimental model of SAH. Female spontaneously hypertensive rats(SHR) were allocated into 4 groups:sedentary ovariectomized(OS, n = 8), trained ovariectomized (OT, n = 8), sedentary ovariectomized treated with hydrochlorothiazide(OSH, n = 8) and trained ovariectomized treated with hydrochlorothiazide(OTH, n = 8). Ovariectomy was performed on the first day of the study. Hydrochlorothiazide(30 mg/kg) was dissolved in the drinking water. The OT and OTH groups were submitted to CET with intensity of 40-60% of maximum capacity,3 days per week, during 8 weeks. In the seventh week, all rats were kept in metabolic cages during 24 hours for urine collection. In the sequence, the rats underwent cannulation of the carotid artery for direct BP recording. Both trained groups showed an increase in their performances when compared to their initial tests, and to the sedentary groups at the end of the protocol(p < 0.0001). Furthermore, OTH group showed an additional increasing when compared to the OT group at the end of the protocol in the maximal load test (p < 0.0001). The OSH, OT and OTH groups presented lower systolic(OSH:189.0 +- 13; OT:179.3 +- 5; OTH:174.1 +- 15), diastolic(OSH:138.9 +- 7; OT:131.3 +- 11; OTH:127.6.1 +- 14) and mean BP(mmHg) (OSH:163.0 +- 9; OT:154.3 +- 13; OTH:149.8 +- 14) when compared to the OS group (SBP:207.6 +- 15; DBP:155.4 +- 18; MBP:180.2 +- 8). The OT group(332 +- 20) presented resting bradycardia (bpm) compared to the sedentary groups(OS:380 +- 25; OSH:374 +- 28). The OTH group showed reduced plasma creatinine levels in relation to the OS group(p < 0.0001). In addition, hydrochlorothiazide combined or not with CET induced higher clearance of creatinine when compared to the OS group(p = 0.0029). Plasma urea levels were similar between groups. The results suggest that the association of CET and pharmacological treatment can promote additional cardiorenal benefits in post menopaused rats, suggesting an important role of the combination of these therapies, probably impacting on quality of life and SAH-related risk factors and morbimortality. 111664 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Distribution of Death from Acute Myocardial Infarction in Brazil MATHEUS SOUZA DA SILVA1, Jessica Haline de Souza dos Reis1, Thalles Franklin Souza Santos1, Daniel Ferreira Cunha1, Lucca Dal Moro1, Carlos Lutian da Silva Andrade1, Bruno Artur de Almeida Santos1, Lucas Gama Pacheco1, Kamylla Batista Brito1, Raul Antonio Lopes Silva Campos1, Joao Marcos Rodrigues Silva1, Luciano Moura de Assuncao2 (1) Universidade Federal do Para; (2) Fundacao Santa Casa de Misericordia do Para Introduction: Pre-hospital care aims to reduce the time between the onset of an ischemic event in the myocardium and effective treatment. It is at this point that mortality in the first few hours can be reduced (1). Therefore, a good quality of care and adequate management of cases of Acute Myocardial Infarction (AMI) must have a good infrastructure, which is closely related to the number of deaths. Knowing the complexity and differences between the different care contexts by regions, the present study compares the number of deaths from AMI and the number of hospitalizations by regions in Brazil. Objectives: To establish a quantitative analysis on the ratio of the number of deaths to the number of hospitalizations due to AMI and to compare the results by regions of Brazil. Methods: The study is a cross-sectional, retrospective, descriptive and quantitative analysis carried out based on data obtained from the Department of Informatics of the Unified Health System (DATASUS) for Brazil, with a temporal analysis between the period 2015 and 2019. Results: Between 2015 and 2019, there were a total number of 571,473 hospitalizations for AMI in Brazil; being 24,158 in the North Region; 111,422 in the Northeast Region; 283,438 in the Southeast Region; 113,733 in the South Region and 38,722 in the Midwest Region. Of which, 61,499 died in Brazil; 2,892 in the North Region; 13,476 in the Northeast Region; 29,699 in the Southeast Region; 11,392 in the South Region and 4,040 in the Midwest Region. Of the total number of hospitalized patients by region, 10.76% died in Brazil, 11.9% in the North, 12% in the Northeast, 10.47% in the Southeast, 8.79% in the South and 10.43% in the Midwest Region. Thus, there were 9.29 hospitalized for each death in Brazil; 8.3 hospitalized for each death in the North Region; 8.2 hospitalized for each death in the Northeast Region; 9.5 hospitalized for each death in the Southeast Region; 9.98 hospitalized for each death in the South Region and 9.58 hospitalized for each death in the Midwest Region. Conclusions: In view of the results, it can be concluded that the North and Northeast regions have a higher ratio of deaths due to hospitalization due to AMI and do not follow the national average for the same statistics. As a limitation of the study, data referring to out-of-hospital deaths from AMI are highlighted. 1.Myerburg RJ, Castellanos A. Cardiac arrest and sudden death. In: Braunwald E. Textbook of cardiovascular medicine. Philadelphia. 111679 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cognitive Profile Among Smokers with Chronic Conditions in the Smoking Cessation Process MARIA FERNANDA MONTEIRO LAMAS1, Beatriz Stephan Faraht Jorge1, Paula Gouvea Abrantes1, Pedro Drumond Maia1, Ramon Jose Moreira Silva1, Rodrigo Maximo Silveira1, Samuel Barud Massensine1, Rafael Matoso de Oliveira Figueiredo1, Amanda Goncalves Vieira Martins1, Bianca de Fatima Pereira1, Arise Garcia de Siqueira Galil1, Eliane Ferreira Carvalho Banhato2 (1) Universidade Federal de Juiz de Fora - UFJF; (2) Centro Universitario UniAcademia Introduction: Tobacco is responsible for 4 milion adults death per year. The tobacco problem seems to be concerned with changing the cognitive system as well as the use of cognitive function Impairments skills are designed by psychometrically valid brief screening instruments. Montreal Cognitive Assessment (MoCA), Clock Drawing Test (CDT) and Verbal Fluency (VF) are validated tests that provide information particularly on cognition such as proven activities, planning, decision making and impulse control. Goal: Identify the cognitive profile of smokers participating in a smoking cessation program, using neuropsychological screening tests. Methods: Longitudinal study, "Livres do Tabaco" group, Cardiology Service, Federal University of Juiz de Fora, Juiz de Fora/Minas Gerais. Users with multimorbidities were treated between September/2021 and March/2022, in consecutive treatment groups, mixed intervention (in person and telemedicine), multidisciplinary team, cognitive behavioral approach sessions, drug treatment and follow-up. Definitions: Cognitive deficit, Montreal Cognitive Assessment <26 points (CDT and VF, inserted in MoCA) was used. Low level of education <8 years. Results: Sample of 36 smokers, equivalent to 6 consecutive treatment groups. Women, 66.7%; 8 years or more of schooling, 57.1%; 65.7% were not in a stable relationship. Age, 56.64 +- 10.61 years. Number of cigarettes smoked daily, 22.77 +- 14.64 cigarettes; high nicotine dependence, 68.6%. As for the cognitive profile, there was low performance on the MoCA (79.4%). In the VF, 55.9%; in the CDT, 19.4%. Age was correlated negatively with MoCa (r = -0.508, p = 0.002) and positively with years of addiction (r = 0.791, p = 0.000) and pack years (r = 0.426, p = 0.011). The CDT was negatively correlated with age (r = -0.479, p = 0.008) and years of addiction (r = -0.602, p = 0.000). Verbal Fluency was correlated negatively with years of addiction (r = -0.353, p = 0.040) and pack years (r = -0.409, p = 0.016). Conclusion: The negative and significant association among variables related to smoking history and cognitive tests showed the presence of cognitive impairment in the studied sample. It is possible that the impairment in planning and decision-making capacity is an important barrier to the difficulty of smoking cessation among smokers with the characteristics described. 111678 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Inequities and Inequalities in the Treatment of Acute Coronary Artery Disease: Comparison between the Private Network and the Public Health System JEFERSON DOS SANTOS1, Suelen Maiara dos Santos1, Luiz Fernando Souza Santos1, Anisia Vieira Souza Fontes3, Aline Barreto Hora2, Thiago Vaz de Andrade2, Matheus Jhonnata Santos Mota2, Victoria Rafaela Nunes dos Santos2, Carlos Felipe Amado Abud2, Jullia beatriz araujo souza2, Karenn santos souza cruz2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe; (3) Centro Universitario Uninassau Introduction: Due to the efforts and efforts of the Brazilian Society of Cardiology (BSC), with national records, it is possible to ensure detailed data that allow us to analyze the differences between public and private hospitals in the care provided and outcomes of patients with Acute Coronary Syndrome (ACS). Objectives: To determine differences in patient characteristics, access to well-equipped services, treatment offered, and intra-hospital and 12-month outcomes between public and private hospitals in Brazil for patients with acute coronary syndrome. Method: This is a prospective observational study that included inpatients diagnosed with ACS in 47 Brazilian hospitals. Patients were followed from admission to discharge and then follow-up was performed by telephone contact at 30 days after discharge, 6 months after discharge and 12 months after discharge. Clinical, personal (previous history) and index event data were collected, such as medical prescription and occurrence of major cardiovascular events (cardiovascular mortality, reinfarction and stroke). The current series compared the results obtained by the population using the Public Health System and the population using the private network. Values of p < 0.001 were considered statistically significant. The ACCEPT registry included, from August 2010 to April 2014, a total of 5,047 patients, making it the largest prospective registry ever published with ACS in Brazil. For the present analysis, all patients who completed the 12-month follow-up (n = 4375) were considered. This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: Patients treated in the Public hospitals had less direct access to a specialized service, with a greater number having to be transferred (38.9%; p < 0.001), in addition to spending more days in the hospital (after 7 days, 40.7% were still hospitalized p < 0.001) and death in this subgroup also showed a statistical difference, both in the period of hospitalization and at 12 months after discharge. Conclusion: In Brazil the management of patients with Acute Coronary Syndrome is influenced by the type of health service, public or private. Patients were more likely to have worse outcomes in public hospitals. 111682 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Regional Spending on Rheumatic Fever in Adults in Brazil and Mortality Rate: Is There a Correlation? SILVIO CESAR ALVES DO NASCIMENTO JUNIOR1, Karimi Mohamed El Bacha1, Karine Corcione Turke2 (1) Universidade Nove de Julho - Sao Bernardo do Campo; (2) Faculdade de Medicina do ABC Introduction: Rheumatic fever is a prevalent disease in our country, with an incidence of 30,000 people/year in Brazil. This disease is directly related to environmental and economic factors, and it is known that it is a disease with a higher prevalence in regions with less financial conditions. The disease can be responsible for several long-term consequences. There are few studies that link expenditures of the Sistema Unico de Saude (SUS) with deaths from rheumatic fever in adults. Objectives: Correlate spending on rheumatic fever in SUS and late mortality associated with the disease in different administrative regioes od Brazil. Methods: Ecological study. The data collected through the DATASUS platform. SUS spending on rheumatic fever and deaths from this disease were evaluated through the Sistema de Informacoes Hospitalares for each administrative region of the country in adults over 20 year old. Obits were adjusted by age group and were stratified by sex, age group and region. For correlations, the Pearson or Spearman tests were used depending on the normality of the data, assessed by Shapiro-Wilk. Results: Throughout the period of 2008 to 2016, were reported 6254 deaths from rheumatic fever in Brazil in adults over 20 years and the central-west region had the highest mortality rate (0,63:100.000). No correlation was found between the overall mortality rate and SUS spending with rheumatic fever (cor: 0.374, p = 0.32). A strong and positive correlation was observed between mortality and outgoing in the northeast region (cor: 0.853, p = 0.003) and central-west (cor: 0.757, p = 0.018). In addition, no correlation was observed between mortality and HDI (cor: 0.552, p = 0.333). No correlation was found by age group or gender. Conclusion: In this study, it was possible to observe that there was no correlation between regional costs and mortality from rheumatic fever in the country, however, central-west and northeast a correlation was found. In view of the above, this correlations show a significant cost associated with higher mortality. In this way, we can assume that the investment these regions receive, there is a right mortality rate from rheumatic fever in adults, what can reflect an ineffective distribution of resources in these places. 111692 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Inequities and Outcomes in Patients with Myocardial Infarction: Public Network Versus Private Network SUELEN MAIARA DOS SANTOS1, Jeferson dos Santos1, Luiz Fernando Souza Santos1, Aline Barreto Hora2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe Introduction: In the last decade many scholars have been concerned about the differences in treatment (acute and intermediate) offered by the public and private health systems, particularly for patients with Acute Myocardial Infarction (AMI), who belong to the group cardiovascular disease - the leading cause of death in the world. Objectives: The present study aimed to compare population subgroups in order to evaluate the access to health care based on clinical recommendations and the difference in clinical outcomes of patients affected by Acute Coronary Syndrome (ACS), who participated in the ACCEPT Registry, comparing them with regard to the type of service (Public Network versus Private Network). Method: The present study compared the results obtained by the public system user population and the private network user population. Values of p < 0.001 were considered statistically significant. The ACCEPT Registry included, from August 2010 to April 2014, a total of 5,047 patients, making it the largest prospective registry ever published with ACS in Brazil. This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: In both subgroups, there was a predominance of males (Private Network: 65.8%; Public Network: 69.9%). Regarding risk factors, smoking (current or previous) showed a significant difference in patients from the Public Network (63.5%; p < 0.001), as well as dyslipidemia (59.2%; p < 0.001) and sedentary lifestyle. (62.6%; p < 0.001) in patients from the Private Network. Patients treated in the Public Hospitals had less direct access to a specialized service, with a greater number having to be transferred (38.9%; p < 0.001), in addition to spending more days in the hospital (after 7 days, 40.7% were still hospitalized; p < 0.001) and death in this subgroup also showed a statistical difference, both in the period of hospitalization and at 12 months. Patients affected by the group of diseases that constitute the Acute Coronary Syndrome who need to use the Public Health System are more likely to spend more time in hospital and have worse in-hospital outcomes and after 12 months. Conclusion: The need to be transferred to a specialized service seems to contribute to this difference. Thus, in the face of this unequal access to health care, the need for robust, effective and effectively health policies for all is evident. 111694 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Deaths from Heart Failure and Arrhythmias Recorded in Sao Paulo from 2010 to 2019. is There an Increase in Incidence After the Beginning of the COVID-19 Pandemic? SILVIO CESAR ALVES DO NASCIMENTO JUNIOR1, Natalia Gil Prado1, Uelra Rita Lourenco1 (1) Universidade Nove de Julho - Sao Bernardo do Campo Introduction: On March 11, 2020, the World Health Organization declared a COVID-19 (Coronavirus Disease - 2019) pandemic. Data from April 21, 2021 record 14.12.,795 confirmed cases and 381.475 deaths across the country. It is known that there is a correlation between cases of patients infected with COVID-19 and heart disease. However, there are few studies that show an increase in numbers of cases of heart failure (HF) and arrhythmias in adults in the state of Sao Paulo (SP) after the beginning of the pandemic in Brazil. Objectives: To analyze the incidence of deaths from HF, conduction disorders and arrhythmias registered in the Health Unic System (SUS) from Jan/2010 to Dec/2019, and 2020 when the COVID-19 pandemic was declared. Methods: Ecological study. Data were collected through the DATASUS platform. Deaths from HF, conduction disorders and arrhythmias were evaluated in the SUS through the Hospital Information System (SIH/SUS) for the state of Sao Paulo in adults over 20 years of age. Deaths were adjusted by year of care and were stratified by sex, age group and administrative region. For the analysis, hypotheses were used, associated with a t-Student test, when deriving the normality of the data. Results: From 2010 to 2019, 283.834 deaths from HF, conduction disorder and arrhythmias were reported in Brazil in adults over 20 years of age, with 76.190 cases registered in the state of SP, mortality rate (16:100.000). There was no correlation between deaths in 2010 to 2019, and 2020, when the pandemic was declared, recorded in the SUS. However, a probability associated with a t-Student test was observed, with a two-tailed distribution (p: 0.00793), with no significant incidence. When stratified by sex, the mean was 7567.63 (M: 49.90%; F: 50.1%), 80% among the population over 50 years old. Conclusion: It was observed that there was no higher incidence of deaths from HF, conduction disorder and arrhythmias in the pre-pandemic period and the total number of deaths in 2020. However, a slight increase was found when compared to the average mortality in the years 2010 to 2020. 2020 between men and women, and also in older populations. Therefore, it is known that more women die from these diseases in SP. In view of this, cross-sectional studies can be carried out to prove whether there is a relationship between the number of deaths from these pathologies in the post-pandemic. 111695 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Relationship between Neck Circumference, Neck-to-Height Ratio and Arterial Stiffness in Hyperlipidemic Patients RAPHAELA PAULA PINHEIRO1, Carlos Renato de Oliveira2, Allice de Souza Rodrigues1, Maria Julia Montebeller Meneses1, Renato Jorge Alves3 (1) Santa Casa de Sao Paulo School of Medical Sciences; (2) Santa Casa de Misericordia de Sao Paulo Hospital, Cardiology; (3) Santa Casa de Sao Paulo School of Medical Sciences; Santa Casa de Misericordia de Sao Paulo Hospital, Cardiology Background: Hyperlipidemia is an important cardiovascular risk factor. Pulse wave velocity (PWV), the gold standard to assess arterial stiffness (AS), can detect subclinical atherosclerosis with accuracy, however, it's a high-cost tool. Neck circumference (NC) and neck-to-height ratio (NHR), inexpensive and easily obtainable anthropometric measurements, may be associated with AS. Aims: To evaluate the relationship between NC, NHR, and AS assessed by PWV in treated hyperlipidemic patients. Methods: We performed a cross-sectional study with 47 hyperlipidemic patients, over 18 years. Excluded those with cervical anatomical abnormalities. Brachial PWV (bPWV) was obtained by a non-invasive oscillometric method. NC and NHR were assessed. Data were present as frequency (%) or mean +- S.D., used Pearson correlation for analyses, P-value:5%. Results: Sample: 53,2% woman, mean age of 63,6 +- 13,2 years, 63,8% Fredrickson's phenotype IIa, 63,8% used high-potency statin, 87,2% hipertensives, 14,9% current smokers. On average, patients were overweight (BMI 28 +- 3,5). Mean NHR of 23,5 +- 1,8 cm/m, NC of 37,6 +- 3,8 cm, bPWV of 9,3 +- 2,2 m/s; * bPWV was positively associated with NHR (figure 1), but not with NC (r = 0.083; p = 0.580); * Age (years), a well-established risk factor for increased AS, was strongly correlated with PWV (r = 0.962, p = 0.000) and was also associated with NHR (r = 0.386, p = 0.007). Conclusion: Our findings suggest that NHR, but not NC, was positively associated with bPWV in hyperlipidemic patients and might be an inexpensive potential predictor of arterial stiffness, contributing to the clinical follow-up, and preventing cardiovascular events in this population. 111700 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Outcomes in the Care of Patients with Acute ST-Elevation Myocardial Infarction in the Public Health System LUIZ FERNANDO SOUZA SANTOS1, Jeferson dos Santos1, Suelen Maiara dos Santos1, Aline Barreto Hora2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe Introduction: Although we have records that observe patients with Acute Coronary Syndrome (ACS), there is still a lack of studies that show the differences between the public and private service in the care of patients with ACS, in particular the presentation of STEMI (ST-Elevation Myocardial Infarction). The present study aimed to investigate the differences in acute treatment and the presence of outcomes after 12 months of patients affected by STEMI, who participated in the ACCEPT Registry, comparing them with regard to access: Public versus Private Network. Method: The ACCEPT Registry is a prospective observational study that included inpatients diagnosed with ACS in 47 Brazilian hospitals. Patients were observed from admission to discharge and then followed up for 12 months. Clinical data, previous history and index event, such as medical prescription and occurrence of major cardiovascular events (cardiovascular mortality, reinfarction and stroke) were collected. The current study compared the results obtained by the public system user population and the private network user population, specifically affected by the STEMI. Values of p <= 0.01 were considered statistically significant. The ACCEPT Registry included a total of 5,047 patients from August 2010 to April 2014, making it the largest prospective registry ever published with ACS in Brazil. For the present article, only patients with STEMI were considered (n = 1550), which corresponds to the most common diagnosis of ACS (35.8%). This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: Patients treated in the public health service spent more days hospitalized (after 7 days, 40.7% were still hospitalized) and the death rate in this group was 12.3% in 1 year. Age and diabetes were independently associated with the occurrence of major cardiovascular events. Patients with STEMI who need to use the Public hospitals are more likely to spend more time in hospital and have worse outcomes 12 months after the event. Conclusion: The need to be transferred to a better equipped service seems to contribute to this difference. Thus, there is a need to understand in a better way these variables that impact the dichotomy between services, as well as the implementation of strategies that ensure adequate patient management. 111702 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Independent Assessment of the Atrial Fibrillation - Hypertrophic Cardiomyopathy Score in a Brazilian Cohort HENRIQUE IAHNKE GARBIN1, Fernando Luis Scolari2, Felipe Costa Fuchs2, Edileide de Barros Correia3, Beatriz Piva e Mattos2 (1) Post-Graduation Program in Cardiology and Cardiovascular Sciences, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; (2) Division of Cardiology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; (3) Division of Cardiomyopathy, Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil Background: Atrial fibrillation (AF) is a common arrhythmia in hypertrophic cardiomyopathy (HCM), frequently related to adverse outcomes. The AF-HCM point-score is a recently validated predictive model for the assessment of AF risk. Objectives: We sought to independently evaluate the novel AF-HCM score in a tertiary HCM center cohort in Brazil. Methods: A longitudinal HCM cohort followed between 2007-2022 was retrospectively stratified for new onset AF, according to the presence of left atrial dimension (+2 points per 6 mm increase), age at clinical evaluation (+3 points per 10-year increase), age at HCM diagnosis (-2 points per 10-year increase) and heart failure symptoms (+3 points if symptomatic). The AF-HCM score was classified as low (<1,0%/year; score <=17), intermediate (1,0-2,0%/year; score 18 to 21), and high risk (>2,0%/year; score >=22) for AF development. Cox regression model and Kaplan-Meier survival free from AF were analyzed, P < 0,05. Results: A total of 116 patients, aged 56 +- 13 years, 64 (55%) females, were followed for 7.0 +- 5.5 years. The left ventricular maximal wall thickness was 18 +- 3 mm, the left atrial diameter 46 +- 6 mm, 46 (40%) subjects were in NYHA class I, 49 (42%) in class II and 21 (18%) in class III. The AF-HCM score stratified risk as low in 13 (11%) individuals, as intermediate in 49 (42%) and as high in 60 (52%). Over the follow-up, 37 (32%) were diagnosed with AF. Among those with newly diagnosed AF, none was classified as low risk, 14 (38%) as intermediate and 23 (62%) as high, P = 0.027. The area under the ROC curve to detect AF was 0.671 (95% CI 0.565-0.777, P = 0.003). The Kaplan-Meier curve showed that patients in intermediate and high-risk were more likely to develop AF [P (Log-Rank) <0.001]. The intermediate and high-risk groups were associated with developing arrhythmia with a hazard ratio of 56.8 (95% CI 3.4-944.6), P = 0.005. The specificity and the negative predictive value were 100%. On the contrary of the previous North-America study population, most patients of the Brazilian cohort were in the high-risk category (37% vs. 52%). Conclusion: The AF-HCM score is a reasonable tool for recognizing patients not prone to develop AF among those stratified as low risk in a Brazilian cohort. However, the model was limited to identify intermediate and high risk individuals in contrast to the previously stratified North-American population. 111708 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Risk Factors Related to the Development of Preeclampsia and the Importance of Early Identification in Prenatal Care BARBARA BRANDAO LOPES1, Barbara Brandao Lopes1, Joao Joadson Duarte Teixeira1, Maria das Gracas da Silva Guerreiro2, Nadya dos Santos Moura5, Ivana Rios Rodrigues1, Rebeca Silveira Rocha3, Maria Luziene de Sousa Gomes1, Weslley Tiago Sousa Alves4, Barbara Gomes Santos Silva1, Monica Oliveira Batista Oria1 (1) Universidade Federal do Ceara - UFC; (2) Universidade Estadual do Ceara - UECE; (3) Maternidade Escola Assis Chateaubriand - MEAC/UFC; (4) Prefeitura Municipal de Fortaleza - PMF; (5) Universidade Federal do Piaui - UFPI Introduction: Hypertensive disorders occupy the first place in the ranking of causes of maternal deaths in developing countries, as well as being responsible for about 14.0% of all maternal deaths in the world, especially preeclampsia (PE). Despite the lack of knowledge about the etiology of PE and the complexity of its pathophysiology, some factors are related to the development of the disease. Therefore, the early identification of risk factors and the correct management of pregnant women at risk of preeclampsia is a decisive factor in the maternal-fetal clinical outcome. Objective: To investigate the risk factors and maternal characteristics for the development of preeclampsia in pregnant women. Method: Prospective cohort study carried out in 18 Primary Health Care Units in the city of Fortaleza, Ceara, Brazil between March 2018 and February 2020. The study population consisted of pregnant women captured in the 1st gestational trimester, being followed up until postpartum. Sociodemographic, clinical and obstetric data were collected using a form and processed using the Statistical Package for Social Sciences (SPSS) version 24.0 and R software version 3.5.5. Study approved by the Research Ethics Committee of the Federal University of Ceara, according to opinion number 2.448.308. Results: Final sample consisted of 146 patients, of which 39 developed preeclampsia (26.71%). No sociodemographic and clinical aspects were associated with preeclampsia. However, obstetric data such as previous hypertensive disorder (p = 0.03), family history of preeclampsia (p = 0.007) and body mass index (p = 0.01), with a mean of 28.52 (SD +- 7,32) had a strong relation with preeclampsia. Conclusion: In prenatal care, the identification of risk factors related to the development of PE is essential, in order to early identify pregnant women at greater risk for the disease and offer them specialized follow-up, with actions aimed at reducing maternal and perinatal morbidity and mortality. 111847 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Office Long Term Systolic Blood Pressure Variability Before and After a Cerebrovascular Event LARA CABRITA1, Ana Joao Taveira2, Andre Gomes Roque3, Estela Cabral4, Pedro Damiao5 (1) USF Fenix de Aveiro; (2) UCSP Mira; (3) USF Santa Joana; (4) USF Atlantico Norte; (5) USF Fenix de Aveiro Introduction: Cerebrovascular disease (CVD) is a major morbidity and mortality cause. Systolic blood pressure (BP) is classically referred to as a predictor of cerebrovascular events (CVE), and clinical attention is generally given to the mean values of SBP. However, several studies have shown that blood pressure variability (BPV) is a predictor of hypertension mediated organ damage, CVE, and all-cause mortality. Objective: Our study aims at describing long term systolic BPV distribution based on different combinations of modifiable cardiovascular risk factors, before and after a CVE. Methods: We performed an exploratory data analysis on a convenience sample of patients with previous CVE (stroke and transient ischemic accident (TIA)), from a single primary care center. Data was obtained from clinical registries in the software in use on our center. The variables included were age, sex, tobacco use, hypertension, dyslipidemia, obesity, overweight, type 2 diabetes and systolic blood pressure. BPV was calculated as the variability coefficient from the closer 3 systolic BP measures pre and post event, to a maximum of 5 years pre and post event. Statistical analysis was performed with R(r) software and presented in cardinality boxplots. We compared before and after BPV with the Wilcoxon test. Results: Our initial sample included 255 patients with cerebrovascular events, from which only 80 had a minimum of 3 office BP measurements pre and post CVE, and as such were eligible for systolic BPV analysis. Blood pressure target met (defined as systolic BP below 140 mmHg) proportion of patients, pre and post CVE, were 0.475 and 0.508, respectively. No significant differences were found between pre and post event BPV (p = 0.78 global events; p = 0.99 for stroke; p = 0.38 for TIA). No trend was identified for post event reduced BPV for a single or combinations of risk factors. Conclusion: Our study shows that office long term BPV does not vary before and after a CVE. However, in our sample, systolic BP mean proportion of patients that meet the recommended target also remains the same after a CVE, probably meaning a lack of control of this important predictor. This study has major limitations, being observational with a small sample of patients, which renders definite conclusions for the relevance and eventual change of BPV before and after cerebrovascular events. However, it clearly shows that there is a need to improve risk factor goal attainment after a CVE. 111716 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Rheumatic Mitral Valve Disease: Repair or Replacement? LUIS HENRIQUE OLIVEIRA PEREIRA1, Kelvin Camara1, Tamires Santos Pinheiro1, Matheus Monaco Lemos1, Ana Laisa Andrada Oliveira2, Maria Eduarda Pereira de Oliveira3, Gabrielly Machado Trindade4, Marjorie Francisca Raksa1, Manoel Flavio Silva Kanisky1, Gerlanio Cesar da Silva1, Valdano Manuel5 (1) Universidade Centro de Ensino de Maringa (UNICESUMAR); (2) Faculdade Pernambucana de Saude (FPS); (3) Universidade Vila Velha (UVV); (4) Centro Universitario Max Planck (UniMax); (5) Clinica Girassol, Complexo hospitalar de doencas cardio-pulmonares Cardeal Dom Alexandre do Nascimento, Instituto do coracao (InCor) do Hospital das Clinicas da Universidade de Sao Paulo Introduction: Rheumatic heart disease (RHD) remains a public health problem, especially in developing countries. The mitral valve is the main affected cardiac structure, requiring intervention in many cases. The discussion of the best intervention is still a controversy; repair or replacement. Objectives: This systematic review aims to evaluate the survival of patients with RHD submitted to valve replacement or repair. Method: We systematically reviewed the English literature through PubMed, LILACS, SciELO and Google Scholar between January 1, 2021, and February 28, 2022, based on PRISMA methodology. Articles with a sample of at least 30 patients under 66 years-old who underwent mitral valve (MV) replacement or repair were included. The articles were classified by Newcastle-Ottawa Scale. Results: Six studies including 2874 patients were analyzed. Most of the patients were female (2001; 69.6%) with a ratio of 2.30:1 for female:male. The age ranged from 11 to 66 years old, being 10 to 65 years old in the repair group and 12 to 66 years old in the replacement group. The mean follow-up time varied from six to 106 months. In MV repair group, the mortality was 3.2% and reoperation was 6.2%, while in the MV replacement the mortality was 7.5% and 3.2% required reoperation. Patient's survival was found to be similar (85% for repair and 87% for replacement). About the main complications post-MV repair and MV replacement, respectively, were: stroke (1.8%, 2.5%) and endocarditis (0.5%, 1.3%). One article, composed by 148 patients, compared datas between mechanical and bioprosthetic surgical replacement: mortality (2%, 17%), reoperation (5.6%, 5.2%) and survival in four years (98% +- 2%, 70% +- 10%), in that order. The article also presented that the main general complications were stroke (0%, 5,2%) and endocarditis (1%, 4%). Conclusion: MV repair demonstrated lower mortality in patients compared to MV replacement, even though it had a higher rate of reoperation. These facts support the idea of shared decision with the heart team and the patient, considering their clinical status, life expectancy, measuring risks and benefits of the surgical decision. 111731 Modality: E-Poster Young Researcher - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Benchmarking Analysis of a Single Centre PFO Closure Program: Comparative Study using the Reduce Trial Data HENRIETTE MESZAROS1, Pal Abraham1, Andrea Agnes Molnar1, Dorottya Pasztor1, Sandor Nardai1, Bela Merkely1, Bela Merkely1 (1) Heart and Vascular Centre of Semmelweis University Introduction: Half of the cryptogenic strokes are attributed to persistent foramen ovale (PFO), their transcatheter closure significantly reduces the risk of recurrent stroke. Aims: We aimed to do a comparative analysis of the baseline clinical and follow up data from our PFO closure patients with the data from the largest randomized trial on PFO(441 patients). Methods: We prospectively enrolled 105 patients in our single-centre registry who had PFO-closure between January 2018 and March 2021. We analysed retrospectively their baseline clinical data, PFO anatomy, procedural outcome and prospectively arrhythmias, device-related complications, and recurrent stroke events during a median follow-up time of 585 days. Data was compared to the published data from the PFO-closure arm of the REDUCE. Results: The mean age of the patients(45 +- 10.6 vs.44.4 +- 9.3(p = 0.56); and the distribution of genders was similar(males 64% 67/105 vs.59.2% 261/441; p = 0.44). More of our patients had hypertension(42.9% 45/105vs.25.4% 112/441p = 0.0007), and were smokers(36.2% 38/105vs.14.3% 63/441 p = 0.001), the prevalence of diabetes (4.7% 5/105 vs.4.1% 18/441(p = 0.80) and the proportion of complex PFO-s was similar(57.2% 57/105 vs.42.8% 268/441 p = 0.23). The success rate of closures was similarly high:91.4% 96/105 vs.93.7% 413/441 p = 0.40. Device dislocation occured in 1 patient vs.in 3 patients(0.9% 1/105 vs.0.6% in 3/441 patients p = 0.58). No recurrent stroke occurred in our cohort, while 5 patients (1.2%) had stroke in REDUCE in the first 2 year follow-up period, this difference is non-significant. 1 of our patients(0.9%) had postoperative paroxysmal atrial fibrillation, while 29 patients(6.6%) of the REDUCE cohort, however their follow-up time for arrythmias was longer, therefore this data is not comparable. Conclusion: The short and midterm outcome of our PFO program yielded similar results to REDUCE, despite treating patients of higher cardiovascular risk. Further follow-up is needed to determine the long-term prevalence of atrial fibrillation, therefore we need imaging markers in the future for to predict the developement of this arrhytmia. 111759 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Rheumatic Heart Disease in Brazil: Effects of the Antibiotic Prophylaxis in Preventing Heart Damage. A Systematic Review GHABRIELA SILVA RABELO1, Ghabriela Silva Rabelo1, Julia Souza Siqueira1, Lorena Oliveira Carneiro2 (1) Universidade Catolica de Brasilia; (2) Universidade Federal do Goias Introduction: One of the most prevalent acquired heart diseases in children and young adults in Brazil is the Rheumatic Heart Disease. When the patient has already been exposed to the patogen and wasn't treated, the use of antibiotic prophylaxis (AP) prevents further complications. Goal: Given the social/economical difficulties and the high incidence of rheumatic disease in Brazil associated with the prolonged period of antibiotic administration, this study aims to understand the impact of the AP in Brazil in preventing heart damage. Methods: A systematic review carried out in accordance with the recommendations of the PRISMA. The databases used in the study were: SciELO, Lilacs and PubMed. Those search descriptors were used: Rheumatic Heart Disease, Brazil and antibiotic prophylaxis. The inclusion criteria consisted of original articles, of free access, published in English and/or Portuguese and that met the objective of the study. Exclusion criteria included reviews and monographs. Results: The total of 5 articles were screened, 1 of which were duplicate; however, only 3 were selected and included in the review, since the study not selected is a narrative review. A cross-sectional study shows a growth of 215% from 1998 to 2016 of the mortality rate from acute rheumatic fever. A randomized clinical trial with children and adolescents with latent rheumatic heart disease were given intramuscular benzathine penicillin G (BPG) every 4 weeks for 2 years or no prophylaxis (control). Among the participants who completed the study, only 0.8% had echocardiographic progression, compared with 8.2% in the control group. A prospective cohort study followed 593 patients with rheumatic fever for 32 years, starting AP with BPG every 3 weeks, in which 10.4% of patients changed treatment to every 4 weeks after turning 21 years of age. This study was divided into two groups, both with AP, the first with patients without cardiac lesions (41%) and the second with cardiac lesions (59%), among these, 17 patients, in irregular AP, were affected by the worsening cardiovascular; however, no patient on regular AP experienced progression of cardiac damage. Conclusions: This study demonstrates the efficiency of regular use of AP to reduce the recurrence of heart damage and the high rates of rheumatic heart disease in Brazil. However, there are few studies comparing the accessibility and effectiveness of the Brazilian prophylactic scheme in relation to international protocols. 111762 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Outcomes in Patients with an Episode of Acute ST Elevation Myocardial Infarction: A Comparative Analysis between the Public Health System and Private Networks LUIZ FERNANDO SOUZA SANTOS1, Jeferson dos Santos1, Suelen Maiara dos Santos1, Aline Barreto Hora2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe Introduction: Cardiovascular diseases represent the main cause of death in Brazil and in the world. Acute Coronary Syndrome (ACS) is one of the presentations of these diseases, with ST elevation acute myocardial infarction (STEMI) being the type with the highest morbidity and mortality. Objective: To assess the correlation between patient outcomes in STEMI episodes between public and private health care networks. Method: The present study used the ACCEPT registry database. Patients with ACS treated in selected Brazilian hospitals were compiled. Only patients with STEMI were considered (Public Network = 1029, Private Network = 521). P-values (Fisher's exact) were reported to three decimal places. This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: Regarding to the clinical outcomes in the first 7 days, there was no significant difference between episodes of reinfarction, stroke and severe bleeding (Table 1). However, there was a difference in death in the first 7 days (Public Network - 3.8%; Private Network - 1%; p = 0.001). Conclusion: It was concluded that there are statistically significant differences between patients who use the Public Network suffering worse outcomes, death showed differences in the two studied moments, while at hospital discharge there was a worse prognosis for SUS users, the other variables were not significant. 111766 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Chagas Disease-Related Mortality in Brazil from 2010 to 2020: Temporal and Spatial Trends MARIANA DA SILVEIRA CASTRO1, Leonardo Sandrini Costa1, Rafaella Quirino Alcantara1, Geovana Oliveira de Paula1, Felilpe Fonseca dos Reis1 (1) Pontificia Universidade Catolica de Goias (PUC-Goias) Introduction: Chagas disease is an infectious tropical disease, caused by the flagellate protozoan Trypanosoma cruzi, transmitted by contact with the feces of vector insects, called "barbeiros" in Brazil, and it reamins still quite neglected. It has a greater distribution in Brazil, reaching about 40% of the territory, and it is estimated that 30% evolve to cardiac and digestive form, the main responsible for the high disease morbidity and mortality. Objective: To analyze the number of deaths from Chagas disease reported in the Brazilian population, between 2010 and 2020. Methodology: Epidemiological, retrospective, descriptive and quantitative study, carried out by collecting data from the Mortality Information System (SIM) on the platform of the Department of Informatics of the Unified Health System (DATASUS). Mortality data from Chagas disease in the Brazilian population were analyzed from January 2010 to December 2020. The sociodemographic and clinical variables selected were: region and Federative Unit of residence, year of death, sex and age group. Results: In the analyzed period, the total of 49.574 deaths from Chagas disease in the entire national territory was recorded, with 26.886 being men and 22.684 women. Most deaths occurred in age group 70-79 years, corresponding to 28,2% of the total. The variation in mortality in this 10-year interval followed a specific pattern, with a decreasing rate of 14,6%, with the year 2020 having the lowest rate with 4.165 deaths, while the year 2010 represented the highest number of deaths, with 4.876. According to the Federative Unit residing, it was observed that Southern remained as the largest holder of deaths from Chagas disease in the country, with emphasis on the state of Sao Paulo. On the other hand, region North presented the lowest number with 2% in relation to the total. Conclusions: It was possible to identify a high concentration of deaths from Chagas cardiomyopathy in the the most populated region of the country, even with a drop in the number of cases in a ten year period. In view of the national perspective, primary care should be further promoted in terms of the access of the Brazilian population to effective diagnosis and treatment of the disease, since they are crucial for improving the quality of life of patients with this disease, as well as for the prevention of its chronic, and even fatal, condition. 111781 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Prognosis of Acute Myocardial Infarction with ST Elevation and Its Associated Factors: Analyzes between the Unified Health System and Private Networks SUELEN MAIARA DOS SANTOS1, Jeferson dos Santos1, Luiz Fernando Souza Santos1, Aline Barreto Hora2, Andreza Oliveira Almeida2 (1) Universidade Tiradentes; (2) Universidade Federal de Sergipe Introduction: Acute ST elevation myocardial infarction (STEMI) is one of the main causes of death caused by cardiovascular diseases. Combined events such as reinfarction, respiratory arrest, severe bleeding and stroke are factors that affect the prognosis of STEMI. Objective: To evaluate events that may contribute negatively to the prognosis of STEMI in the population studied. Method: The present study used the ACCEPT registry database, which selected patients with Acute Coronary Syndrome treated in Brazilian hospitals in all regions. Only patients with STEMI were considered (Public Network = 1029; Private Network = 521). P-values (Fisher's exact) were reported to three decimal places with p-values less than 0.001 reported as p < 0.001. This study was approved by the Research Ethics Committee of the Federal University of Sergipe, under registration number 302.544. Results: In this present study, the variables: attendance at the Unified Health System (SUS), region, age, systemic arterial hypertension (SAH), diabetes, Congestive heart failure (CHF), current smoking and dyslipidemia were the factors that most contributed to the negative prognosis. (Fig. 1). The variables of female sex, reperfusion with primary and non-primary angioplasty only, and thrombolytic-only reperfusion reduce the likelihood of a negative prognosis. Conclusion: Care in the SUS, SAH, CHF, diabetes and current smoking were factors that most contributed to the negative prognosis. 111856 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Cardiac Implantable Electronic Devices in the Brazilian Public Health System: A Real-World Data Study MIRIAM ALLEIN ZAGO MARCOLINO1, Miriam Allein Zago Marcolino1, Rodrigo Antonini Ribeiro2, Luis E. Rohde3, Carisi Anne Polanczyk4 (1) Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; (2) National Institute of Science and Technology for Health Technology Assessment - INCT/IATS (CNPq 465518/2014-1), Porto Alegre, Brazil; (3) Cardiology Center, Hospital Moinhos de Vento, Porto Alegre, Brazil; (4) Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Introduction: Cardiac implantable electronic devices (CIED), including pacemakers (PM), implantable cardioverter-defibrillator (ICD), and cardiac resynchronization therapy (CRT), are interventions long established in the cardiology practice, but restricted for selected patients. They include simple devices to highly complex and costly procedures. Objective(s): To describe the profile of patients that received a CIED covered by the Brazilian public health system (SUS) over a 12-year period. Methods: Retrospective epidemiological study including open data of all hospital admissions with a CIED implantation as primary procedure reimbursed by the SUS between 2008 and 2019, obtained from the Hospital Information System of SUS Informatics Department (DATASUS). Mean annual rate per million population was age and sex standardized by the OMS standard population. All analysis were performed using R. Results: SUS reimbursed 216,440 CIED implant procedures from 2008 to 2019 (mean annual rate of 87.1 per million population), mainly PM (89.3%). Patients mean age was 68.8y (15.3), and were mostly male (54%), residents in the Southwest (45%), South (22%), or Northeast (21%) regions. Arrhythmias diagnoses were present in 87% of the patients, mostly in PM (91%) and ICD (83%). Heart failure was present in 61% of CRT and 38% of CRT-D patients. The mean length of stay was of 4.1 (6.3) days, 1.5% died during hospitalization, and mean hospitalization reimbursement values varied by CIED type (R$8,309 to R$ 56,791). (Table 1) Conclusions: Twelve-year cumulative data indicates that CIED implantation in Brazil was performed mostly on aged patients, males, residents in the Southwest, South or Northeast, PM predominantly. These data might help guide health policy actions on access to CIED therapies. 111871 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Overweight Prevalence and Correlation with Arterial Stiffness and Cardiometabolic Risk Factors in Treated Hyperlipidemic Patients RAPHAELA PAULA PINHEIRO1, Carlos Renato de Oliveira2, Allice de Souza Rodrigues1, Maria Julia Montebeller Meneses1, Renato Jorge Alves3 (1) Santa Casa de Sao Paulo School of Medical Sciences; (2) Santa Casa de Misericordia de Sao Paulo Hospital, Cardiology; (3) Santa Casa de Sao Paulo School of Medical Sciences; Santa Casa de Misericordia de Sao Paulo Hospital, Cardiology Background: Hyperlipidemia is a well-established cardiovascular risk factor. The overweight is associated with low-grade chronic inflammation and is correlated to cardiometabolic risk factors. Pulse wave velocity (PWV), the gold standard for arterial stiffness assessment, can detect subclinical atherosclerosis with accuracy. Studies suggest an association between PWV and nutritional status. AIM To describe the overweight prevalence, and correlate with arterial stiffness assessed by PWV and cardiometabolic risk factors in treated hyperlipidemic patients. Methods: We performed a cross-sectional study. There were included hyperlipidemic patients, over 18 years. Sociodemographic data and clinical background were collected by a standardized questionnaire and medical records. Nutritional status was determined by body mass index (BMI), considering "overweight" BMI >=25 kg/m2 to adults <60 years and BMI >=28 kg/m2 to elderly >=60 years. The brachial PWV was assessed by the non-invasive oscillometric method and the patient's laboratory tests were recently collected by medical records. Data were presented as frequency (%), prevalence(%), or mean +- S.D. Results: Sample: 62 patients. Mean age of 63,9 +- 12,5 years, 53,23% female, 43,5% diabetics, 88,7% hypertensives, 64,5% Fredrickson's phenotype IIa, 67,7% used high potency statin and 64,5% overweight prevalence, mean BMI of 28,8 +- 3,7 kg/m2. Overweight patients presented a lower mean of PWV (8,95 m/s), although higher use of high potency statin (55,65%) when compared to those without overweight (10,06 m/s; 38,46%). The patients with overweight presented higher means of LDL-c (113,7 +- 61,3 mg/dl), total cholesterol (190,3 +- 74,6 mg/dL), triglycerides (202,3 +- 157,7 mg/dL), fasting blood glucose (113,2 +- 40,4 mg/dL), glycated hemoglobin (6,5 +- 1,4%), uric acid (6,2 +- 2,4 mg/dL) and lower means of HDL-c (42,9 +- 11,6 mg/dL), when compared with individuals without overweight (99 +- 30,5; 169,1 +- 47,1; 165,2 +- 100; 108,4 +- 30,3 mg/dL; 6,2 +- 1,0%; 5,7 +- 1,1; 43,1 +- 17,3 mg/dL respectively). Conclusion: The sample had a 64,5% prevalence of overweight, and these individuals presented a worse cardiometabolic profile when compared with individuals without overweight. Contrary to most of the publications, overweight patients presented lower PWV, although they used more high potency statin when compared to those without overweight. Our results may be related to reverse endothelial remodeling, but longitudinal studies can be used to elucidate these correlations. 111884 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Association of Myocardial Function and Pulmonary Hypertension with Maximal Exercise Capacity in Patients with Chagas and Non-Chagas Heart Failure JHESSICA MACIEIRA PEREIRA1, Thayrine Rosa Damasceno1, Rafael Dias de Brito Oliveira1, Enrico De Francisco Magnani1, Danielle Aparecida Gomes Pereira1, Denise Mayumi Tanaka2, Eduardo Elias Vieira De Carvalho2, Julio Cesar Crescencio2, Eduardo Rubio Azevedo2, Marcus Vinicius Simoes2, Luciano Fonseca Lemos De Oliveira1 (1) Universidade Federal de Minas Gerais - UFMG; (2) Faculdade de Medicina de Ribeirao Preto - FMRP/USP Introduction: Increased pulmonary artery systolic pressure (PASP) and reduced left ventricle ejection fraction (LVEF) in individuals with heart failure (HF) is related to disease progression, morbidity and mortality. On the other hand, booth PASP and LVEF are not related to functional capacity (FC). Patients with Chagas HF are known to present worst prognosis and may develop myocardial dysfunction and pulmonary hypertension (PH). However, the association of FC with cardiac function and PH in Chagas HF is still unclear. Objective: To evaluate the association of FC with cardiac function and PH in individuals with Chagas and non-Chagas HF. Methods: Cross-sectional observational study with 178 patients with HF who underwent clinical examination, cardiopulmonary exercise test (CPET) and 2-dimensional echocardiography. The sample was divided between Chagas (CH, n = 101) and non-Chagas (NCH, n = 77) HF. Data normality was analyzed using the Kolmogorov-Smirnov test. Data comparison was verified with Student's t test or Mann-Whitney test. The association was performed by using the Pearson or Spearman correlation coefficients. Results: Compared to NCH group, CH group presented higher VO2peak (16.8 +- 6.1vs 13.8 +- 4.3 ml.kg.min-1, p < 0.001) and LVEF (42.6 +- 18 vs 28.9 +- 9.7%, p < 0.001), lower left atrial diameter (LAD; 43.1 +- 8.4 vs 47.7 +- 7.2 mm, p < 0.001), left ventricle diastolic diameter (LVDD; 59.5 +- 9.1 vs 66.7 +- 9.9 mm, p < 0.001) and PASP (37.3 +- 13.4 vs 51 +- 15 mmHg, p < 0.001), and similar ventilatory efficiency given by the VE/VCO2slope (35.5 +- 10.6 vs 35.8 +- 8.2, p = 0.83). In the CH group, VO2peak correlated significantly with PASP (r = -0.60, p < 0.001), LVEF (r = 0.51; p < 0.001), LVDD (r = -0.36, p < 0.001), LV mass index (r = -0.36, p < 0.001), LAD (r = -0.34; p < 0.001), E wave (r = -0.32; p = 0.01) and TAPSE (r = 0.27, p = 0.04). The VE/VCO2slope was correlated with LVEF (r = 0.53; p < 0.001), PASP (r = 0.46; p = 0.001), LVDD (r = 0.42; p < 0.001), LAD (r = 0.33; p = 0.001), TAPSE (r = 0.3, p = 0.03) and LV mass index (r = 0.21, p = 0.047). In the NCH group, VO2peak was only correlated with TAPSE (r = 0.60, p = 0.013) and LAD (r = -0.25, p = 0.04). Moreover, VE/VCO2slope was not correlated with echocardiography variables. Conclusion: In patients with Chagas HF, PASP as well as myocardial function and morphology impacts the functional capacity of the subjects when compared to patients with different etiologies. In addition, the findings suggest that PH may be related to the disease severity and progression. 111891 Modality: E-Poster Young Researcher - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Profile of Smokers in Abusive use of Alcohol in the Process of Quitting Smoking SAMUEL BARUD MASSENSINE1, Amanda Goncalves Vieira Martins1, Beatriz Stephan Farhat Jorge1, Bianca de Fatima Pereira1, Fernanda Silva Mota1, Gabriela Godinho Rezende1, Moises de Toledo Vilela1, Paula Gouvea Abrantes1, Pedro Drumond Maia1, Ramon Jose Moreira Silva1, Eliane Ferreira Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Cardiology Department, Medical School, Federal University of Juiz de Fora - UFJF Introduction: Smoking and alcohol abuse usually coexist and have synergistic effects, leading those with this duo addiction to worse outcomes than those who only smoke. This culminates in personal and family suffering and high social cost. Then it's important to evaluate the effects of alcohol consumption in smokers. Objectives: To evaluate alcohol abuse (UAA) with clinical characteristics and smoking history, among smokers during the smoking cessation process. Methodology: Longitudinal study, group "Free Tobacco", Juiz de Fora/Minas Gerais. Users with multi-morbidity were treated between September/2021 and March/2022, in consecutive treatment groups, mixed intervention (face-to-face and telemedicine), multidisciplinary team, cognitive behavioral approach (ACC) sessions, drug treatment and follow-up. Definitions: UAA, Audit-C >=5 points. Low level of education, <8 years. Normal systolic blood pressure (SBP) <130 mmHg. Depression, Patient Health Questionnaire (PHQ-9) score >=9 points. Cognitive deficit, Montreal Cognitive Assessment <26 points. High nicotine dependence, Fagerstrom test >=5 points. Results: The sample consisted of 36 smokers with multi-morbidity who participated in a group with a multidisciplinary team, intended for treatment for smoking cessation. UAA was found in 20% of the sample. Comparing these patients with those without this use, they were younger individuals (p < 0.049), with a higher prevalence of abdominal obesity (p < 0.002), arterial hypertension (p < 0.002), of cognitive deficit (p < 0.001) and with a tendency to greater use of crack together (p < 0.063). Allied, they had a lower prevalence of depression (p < 0.031), anxiety (p < 0.021), and curiously, sedentary lifestyle (p < 0.049). As for smoking history, they had greater nicotine dependence (0.001), greater triggers for alcohol itself (p < 0.008), for habits (p < 0.003), but not for the use of coffee (p < 0.019). Allied, greater adherence to meetings for ACC, (p < 0.001). Conclusion: The association between smoking and alcohol consumption is associated with the perpetuation of this addiction and increased consumption of illicit drugs. Screening for alcohol use should be encouraged for all smokers, and interventions aimed at encouraging the cessation of both harmful habits should be the target audience. As it is also associated with other unfavorable outcomes, it is necessary to track and discourage alcohol consumption by smokers. 111922 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSIOTHERAPY Association of Myocardial Changes with Functional Capacity and Effects of Aerobic Physical Training in Syrian Hamsters with Chronic Chagas Cardiomyopathy THAYRINE ROSA DAMASCENO1, Enrico de Francisco Magnani1, Rafael Dias de Brito Oliveira1, Jhessica Macieira Pereira1, Denise Mayumi Tanaka2, Mariana Duarte de Souza1, Jorge Mejia Cabeza3, Camila Godoy Fabricio2, Alessandra Arantes Resende2, Dawit Albieiro Pinheiro Goncalves1, Marcus Vinicius Simoes2, Luciano Fonseca Lemos de Oliveira1 (1) Universidade Federal de Minas Gerais (UFMG); (2) Faculdade de Medicina de Ribeirao Preto (FMRP/USP); (3) Hospital Israelita Albert Einstein Introduction: Chronic Chagas cardiomyopathy (CCC) may present with morphological, functional and myocardial perfusion alterations. However, the influence of these changes in the reduction of functional capacity and the effects of aerobic physical training (APT) on them are still unknown. Objective: To evaluate the association of aerobic capacity with morphology, function and myocardial perfusion as well as to evaluate the effects of APT on such variables in a model of CCC in Syrian hamsters. Methods: Female Syrian hamsters infected with 3.5 x 10000 trypomastigote forms of the Y strain of T. Cruzi (n = 37) and their respective controls (n = 14) were used. Seven months after infection, the surviving animals underwent two-dimensional echocardiography, myocardial perfusion scintigraphy to assess myocardial perfusion defects (PD) and cardiopulmonary testing (CPT). The animals were then divided into 4 groups: Sedentary Chagas (CH-SED, n = 14), APT Chagas (CH-APT, n = 9), Sedentary Control (CT-SED, n = 6) and APT Control (CT-APT, n = 8). The APT was performed for 8 weeks, 5 times a week, for 50 minutes at an intensity equivalent to 50% of the peak velocity evaluated in the TCP. All animals repeated the examinations at the end of the experiment. Results: At baseline, 9 (24%) of the 37 infected animals showed myocardial involvement with reduced left ventricular ejection fraction (LVEF, pANNOVA <0.01), VO2peak (pANNOVA = 0.01) and higher PD (pANNOVA = 0.01) when compared to control and infected animals without cardiac involvement. VO2peak correlated with PD (r = -0.66, p < 0.01), LVEF (r = 0.37, p = 0.02), left ventricular diastolic diameter (LVDD, r = -0.53, p < 0.01) and LV systolic diameter (LVSD, r = -0.49, p < 0.01). In the multiple regression analysis, only PD remained independently associated with VO2peak (r2 = 0.42). After the follow-up period, the mixed analysis of variance showed that the groups submitted to APT and the CH-SED group showed eccentric LV remodeling with an increase in LVDD. However, an increase in LVSD and PD, as well as a decrease in LVEF were only observed in the CH-SED group. In addition, the CH-APT group showed an increase in VO2peak and an increase in the maximum distance covered after the intervention. Conclusion: APT was able to prevent the progression of perfusion defects and LV dysfunction, in addition to improving functional capacity, which is determined by morphology, function and myocardial perfusion in an experimental model of CCC. 111952 Modality: E-Poster Young Researcher - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Correlation between Postoperative Cardiac Risks Factors, Functionality and Length of Stay MICAELE FARIAS NASCIMENTO1, Beatriz Souza de Albuquerque Cacique New York1, Milton Antonio Goncalves de Oliveira1, Katia Elizabete Galdino1, Ana Tereza do Nascimento Sales Figueiredo Fernandes1 (1) State University of Paraiba - UEPB Introduction: Cardiac surgery (CS) may be associated with several organic repercussions responsible for the appearance of cardiac risk factors during the postoperative period. These, associated with prolonged hospital length of stay (LoS), may trigger critical manifestations in individuals undergoing this surgical procedure. Objective: To investigate the relationships between postoperative cardiac risk factors, LoS, and changes in functioning state. Methods: Patients undergoing reconstructive, substitutive, or corrective cardiac surgeries were evaluated. The presence of postoperative cardiovascular risks was assessed using the InsCor score, while LoS and functionality were collected from medical records. Results: One-hundred patients with a mean age of 59.2 +- 12.3 years were included. Significant correlations between functionality and both the hospital and Intensive Care Unit (ICU) LoS (p < 0.0001, r = 0.56; p = 0.002, r = 0.29, respectively), as well as between hospital LoS and the number of comorbidities (p = 0.003, r = 0.28) were found. No significant relationships were observed between the number of postoperative risk factors and LoS. Conclusion: Functionality and comorbidities are associated with increased hospital and ICU LoS in patients undergoing cardiac surgery. 111976 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT ICD Indication in Hypertrophic Cardiomyopathy: Which Algorithm to Use? MANUELLA DE AMORIM SILVA4, Marcelo Antonio Oliveira Santos Veloso3, Gabriela Cisneiros Arcoverde4, Andrea Virginia Chaves Ferreira3, Eveline Barros Calado1, Manuel Markman5, Lucas Soares Bezerra3, Brivaldo Markman Junior1, Dinaldo Cavalcanti de Oliveira3 (1) Hospital das Clinicas da Universidade Federal de Pernambuco HC-UFPE; (2) Servico de doencas raras RARUS; (3) Programa de Inovacao Terapeutica da Universidade Federal de Pernambuco - UFPE; (4) Hospital Alfa de Referencia ao COVID-19 - HRE; (5) Hospital Agamenon Magalhaes - HAM Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in youth. The recommendations for prophylactic implantable cardioverter-defibrillators (ICDs) are divergent. Objective: To evaluate the agreement in the indication of ICD in patients with HCM, as per recommendations of the European Society of Cardiology 2014 and American Heart Association 2020, and evaluate fragmented QRS (fQRS) as a predictor of cardiovascular outcome. Methodology: Retrospective cohort with 81 patients evaluated between 2019 and 2021. Patients with HCM >=16 years old were included. Exclusion criteria: secondary myocardiopathy, follow-up <1 year. Kappa coefficient was used to determine the agreement. Survival and incidence curves were determined by Kaplan-Meier method. A p-value <0.05 was considered significant. Results: The fQRS was identified in 44.4% of patients. There were no differences between patients with and without fQRS regarding clinical parameters, echocardiography, fibrosis and SCD risk. During follow-up of 4.8 +- 3.4 years, there was no SCD, but 20.6% patients with ICD had at least one appropriate shock. Three of the seven appropriate shocks occurred in European Society of Cardiology low-to-moderate risk patients. Three shocks occurred in moderate-risk patients and four in American Heart Association high-risk patients. Overall recommendations agreement was 64% with a Kappa of 0.270 (p = 0.007). C-statistic showed no differences regarding the incidence of appropriate shock (p = 0.644). Conclusion: SCD risk stratification algorithms present discrepancies in ICD indication, both with low accuracy. 111977 Modality: E-Poster Young Researcher - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Descriptive Analysis of the Brazilian Black Population from the First Brazilian Hypertension Registry MAICON BORGES EUZEBIO2, Maicon Borges Euzebio2, Priscila Valverde de Oliveira Vitorino3, Sayuri Inuzuka1, Weimar Kunz Sebba Barroso4 (1) UNIVERSIDADE FEDERAL DE GOIAS UFG; (2) CENTRO UNIVERSITARIO DE MINEIROS UNIFIMES; (3) PONTIFICIA UNIVERSIDADE CATOLICA DE GOIAS PUC GOIAS; (4) LIGA DE HIPERTENSAO ARTERIAL LHA HC UFG Introduction: Several studies have demonstrated a higher prevalence and severity of arterial hypertension (AH) in blacks than in whites. However, this is an aspect related to the epidemiology of AH that has been little studied in Brazil. Objectives: To characterize the Brazilian black population of the first Brazilian Hypertension Registry in relation to anthropometric, clinical and pharmacotherapeutic characteristics. Methods: This is a cross-sectional, multicenter descriptive study of the population subgroup of self-declared black from the First Brazilian Registry of Arterial Hypertension, whose collection was carried out from June 2013 to October 2015. A descriptive analysis was performed and the test was used to verify the data distribution of the variables and adopted as significant p < 0.05. Anthropometric variables were considered: Age, in years; Body mass index (BMI) in kg/m2; Waist circumference (WC) in cm. In the clinical variables, the presence of: Diabetes, Dyslipidemia, Cerebrovascular disease, Cardiac disease, Renal disease, Peripheral artery disease, Smoking, Physical Activity, Alcohol dependence, Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in mmHg, Blood Pressure (BP) on target (cut-point for BP control <140 x 90 mmHg), Glucose, mg/dL, Total cholesterol, mg/dL, HDL-Cholesterol, mg/dL, LDL-Cholesterol, mg/dL and Triglycerides, mg/dL. As a pharmacotherapeutic conduct, the use of: Acetylsalicylic acid, Clopidogrel, Metformin, Insulin and Statins. Results: Of a total of 2,646 participants (Whites, Blacks, Browns and Yellows) from 45 locations in Brazilian regions, 452 (17.8%) declared themselves to be black. The median age was 62.5 years (54.2-69.7), 57.5% were female; BMI 29.8 +- 5.36 and WC 98 (91-106). Dyslipidemia was the main disease in 182 (40.3%) individuals, followed by Diabetes Mellitus 128 (28.3%) and other heart diseases with 93 (20.3%). Smoking was found in 31 (6.9%) participants and 273 (60.4%) reported performing some type of physical activity. The median of SBP was 139 mmHg (128-151), of BPD was 85 mmHg (80-92.6) and the frequency of controlled casual blood pressure in 233 (51.54%) participants. Statins 167 (36.9%), acetylsalicylic acid 148 (32.7%) and metformin hydrochloride 82 (18.1%). Conclusions: The black population evaluated was predominantly female. On average, the body mass index was above the recommended, most had controlled blood pressure and performed some type of physical activity. 111988 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Association of Cardiovascular Comorbidities with Outcomes in Patients Hospitalized for COVID-19 LETICIA DE SOUSA PERES1, Thiago Moreira Bastos da Silva2, Iliana Regina Ribeiro Menezes1, Nathalia Duarte Camisao1, Mariana Moreno Canario da Silva1, Renata Mexias Abdala Felix1, Giovanni Possamai Dutra1, Anna Butter1, Henrique Custodio Goudar1, Glaucia Maria Moraes de Oliveira2, Bruno Ferraz de Oliveira Gomes1, Joao Luiz Fernandes Petriz1 (1) Hospital Barra Dor; (2) UFRJ Background: During the COVID-19 pandemic, cardiovascular comorbidities were associated with greater severity during hospital stay. However, little is known about its association with other long-term outcomes and death. Goals: To assess the association of cardiovascular comorbidities with myocardial injury, lung parenchyma involvement, need for mechanical ventilation, and long-term death in patients hospitalized for COVID-19. Methods: Retrospective cohort study with patients who were hospitalized with a confirmed diagnosis of COVID-19. We evaluated the association of comorbidities diabetes mellitus (DM), arterial hypertension (SAH), chronic kidney disease (CKD) and obesity with the outcomes long-term mortality, in-hospital mortality, myocardial injury, lung parenchymal involvement and use of mechanical ventilation. The variables were evaluated using the chi-square method (categorical variables) and Student's t test (continuous). Results: 1454 patients were included, mean age 59.8 +- 17.0, 62.6% men. There were 269 deaths (18.5%) during the study period (mean follow-up = 338 +- 209 days). 44.7% of patients had myocardial injury. Obese subjects had greater involvement of the lung parenchyma (>50%) than non-obese subjects (18.5 x 12.1%, p = 0.013). However, they had a lower risk of long-term mortality (OR 0.70; 95%CI 0.51-0.96) as well as a lower prevalence of myocardial injury (OR 0.74; 95%CI 0.59-0.94). We observed an association of DM with long-term mortality (OR 2.30; 95%CI 1.75-3.03), in-hospital mortality (OR 2.21; 95%CI 1.65-2.96), myocardial injury (OR 1.49; 95%CI 1.18-1.87) and need of mechanical ventilation (OR 1.92; 95%CI 1.47-2.50). SAH was also associated with long-term mortality (OR 2.87; 95%CI 2.15-3.84), in-hospital mortality (OR 3.25; 95%CI 2.37-4.44), myocardial injury (OR 2.66; 95%CI 2.15-3.30), need of mechanical ventilation (OR 2.42; 95%CI 1.85-3.17) and pulmonary involvement >50% (17.1 x 11.0%, p = 0.005). Finally, CKD was associated with long-term mortality (OR 3.93; 95%CI 2.39-6.44), in-hospital mortality (OR 3.73; 95%CI 2.24-6.20), myocardial injury (OR 5.73; 95%CI 3.10-10.58) and need of mechanical ventilation (OR 2.61; 95%CI 1.58-4.31). Conclusion: In patients hospitalized for COVID-19, SAH, DM and CKD were associated with long-term mortality, as well as myocardial injury and need of mechanical ventilation. On the other hand, obese individuals had lower mortality and less myocardial injury, despite the greater involvement of the lung parench. 112019 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Role of Extracorporeal Membrane Oxygenation in Covid-Related Myocarditis: A Systematic Review MANOEL FLAVIO SILVA KANISKY1, Gerlanio Cesar da Silva1, Kelvin Camara1, Luis Henrique Oliveira Pereira1, Marjorie Francisca Raksa1, Matheus Monaco Lemos1, Tamires Santos Pinheiro1, Ana Laisa Andrada Oliveira2, Gabrielly Machado Trindade3, Maria Eduarda Pereira de Oliveira4, Valdano Manuel5 (1) Universidade Cesumar (Unicesumar); (2) Faculdade Pernambucana de Saude (FPS); (3) Centro Universitario Max Planck (UniMax); (4) Universidade Vila Velha (UVV); (5) Clinica Girassol; Complexo Hospitalar de Doencas Cardiopulmonares Cardeal Dom Alexandre do Nascimento; Instituto do Coracao (InCor) do Hospital das Clinicas da Universidade de Sao Paulo Introduction: COVID-19 can affect the myocardium causing myocarditis. Some patients need ventricular support with Extracorporeal Membrane Oxygenation (ECMO), however, its therapeutic efficacy is not clear yet. Objectives: To know the role of ECMO in patients with myocarditis due to COVID-19. Methods: We systematically reviewed the English literature, searching for patients over 18 years-old on Google Scholar, LILACS and PubMed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), between March 2020 to February 2022. The keywords used were "myocarditis", "COVID-19" and "extracorporeal membrane oxygenation". The quality of the articles was assessed by Newcastle-Ottawa Scale. Results: Ten studies including 609 patients were analysed. Most of them were male (70,6%) and 29,4% female. Age range was 18 to 80 years. Mean follow-up was 103 days (10-180), the length of stay at the intensive care unit was 26 days (0,9-51,9) and at the hospital was 33 days (21-56,6). The average ECMO duration was 15 days (6,5-38,5). Its most used type was venovenous, which was applied to 469 patients; only 19 received venoarterial, in accordance with eight studies. Although three studies did not report weaning rate, 214 patients (35,1%) weaned off successfully, whereas it is estimated that approximately 165 (27%) did not wean. The most relevant ECMO-related complications, evidenced in eight articles, were: bacterial infection (207), acute kidney (156), liver injury (69) and multiorgan failure (11). The global mortality was 216 deaths (35,4%) which varied from three to 63 deaths. Conclusion: Patients with severe COVID-related ventricular dysfunction submitted to ECMO achieved considerable results of successful weaning off, even though the death rate had a significant result. In addition, venovenous intervention demonstrated an effective strategy in selected patients. However, ECMO application still needs further studies to validate the benefits above its negative outcomes in these patients. 112022 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence of Food Insecurity and Its Association with Health Outcomes in Patients with Chronic Chagas Disease CELSON JUNIO DO NASCIMENTO COSTA1, Paula Simplicio da Silva2, Roberto Magalhaes Saraiva2, Andrea Rodrigues da Costa2, Alejandro Marcel Hasslocher-Moreno2, Luiz Henrique Conde Sangenis2, Marcelo Teixeira de Holanda2, Henrique Horta Veloso2, Gilberto Marcelo Sperandio da Silva2, Fernanda Martins Carneiro2, Daniel Arthur Barata Kasal1, Mauro Felippe Felix Mediano1 (1) Departamento de Pesquisa e Ensino, Instituto Nacional de Cardiologia; (2) Instituto Nacional de infectologia Evandro Chagas Introduction: Chagas disease (CD) is a neglected disease that infected 6 to 7 million people worldwide. Individuals with CD are usually from low socioeconomic status and, therefore, more prone to food insecurity (FI). Objective: To assess the prevalence of FI in CD and its association with clinical forms, nutritional status (NS), comorbidities, and biomarkers. Methods: This is a cross-sectional study including patients diagnosed with CD (confirmed by two serological tests), from both sexes. Patients diagnosed with diseases that affect the immune system, other infectious diseases during the data collection period, those using corticosteroids or anti-inflammatory drugs, cancer patients, pregnant women, and cognitive alterations were excluded. The FI was evaluated according to the Brazilian scale of FI (EBIA 2003). The classification of the clinical form of Chagas disease was obtained following the determinations of the Brazilian Consensus on CD (2016). Parameters established by the Brazilian Institute of Geography and Statistics were used to collect the socioeconomic variables. Anthropometric measurements (weight, height, waist circumference) were collected to assess NS. Biomarkers included lipid profile and plasma glucose. Descriptive statistics included mean (standard deviation for numerical) and percentage (frequency) for categorical variables. Comparisons between participants without and with FI were performed using t-test for numerical and chi-squared test for categorical variables. Linear and logistic regression models adjusted by age, sex, education level, and race were fitted to evaluate the association between FI status and clinical forms, NS comorbidities, and biomarkers. Results: Three hundred sixty individuals (56.1% of women) were included in the study, with a mean age of 60.7 (10.8) years. Of those, 30.8% had FI. Participants with FI were more likely to be women, had a lower per capita income, a lower height, a greater percentage of illiterate/incomplete elementary education, and greater frequency of obesity (Table). No significant association was observed between FI and clinical forms of CD, NS, comorbidities, and biomarkers after adjustments for age, sex, education level, and race. Conclusion: Despite the elevated prevalence of FI among patients with CD, no association was observed for health outcomes. Longitudinal studies examining the impact of FI on health parameters and mortality of individuals with CD are warranted. 112038 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Cardiovascular Premature Mortality between Brazilian Cities with Similar Populations but with Different Human Development Index CAMILA DOS SANTOS MOREIRA DE SOUZA1, Dalmo Valerio Machado de Lima1, Christianne Bretas Vieira Scaramello1 (1) UNIVERSIDADE FEDERAL FLUMINENSE UFF Introduction: Cardiovascular diseases (CVD) are the main cause of death in Brazil and worldwide. Socioeconomic determinants of health are considered independent risk factors for its occurrence. The Human Development Index (HDI) summarizes local human development encompassing health, knowledge and standard of living, being important to investigate if it can be reflected in CVD premature mortality. Objective: Considering the relevance of socioeconomic determinants on CVD deaths, the aim of this work was to evaluate premature cardiovascular mortality (30-69 years of age) in two Brazilian cities with similar populations and different HDI. Methods: The ecological observational study evaluated proportionate CVD premature mortality in two cities of Rio de Janeiro State - Niteroi and Belford Roxo - from 2008 to 2019. Populations of these cities encompass about 500,000 habitants and while Niteroi presents a very high HDI (0.837), Belford Roxo presents a medium one (0.684), occupying the 1st and the 71st position in the state HDI ranking, respectively. An Excel spreadsheet was used for data analysis whose significance was accepted if p < 0.05. The local Human Ethics Committee approved the work. Results: Proportionate CVD premature mortality was lower in Niteroi compared to Belford-Roxo throughout the period studied (27.6 +- 1,3% x 33.5 +- 2.1%; p < 0.01). Pearson coefficient indicates a strong correlation between proportionate CVD premature mortality in these two cities despite the absence of statistical significance (r = 0.4072; p = 0.1888). According to HDI, the mean porportionate CVD premature mortality seems to vary between genders, with Belford Roxo presenting a higher proportion in females (34.2%) while Niteroi shows a higher proportion in males (28.3%). Conclusions: Data suggest that socioeconomic determinants may impact CVD premature mortality. It is important to investigate deeply considering ethnicity and gender aspects to allow better discussions of health policies. 112050 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Access to the Healthcare System of Patients with St-Segment Acute Myocardial Infarction: Has There Been a Change During the Covid 19 Pandemic? RHANNIEL THEODORUS HELHYAS OLIVEIRA SHILVA GOMES VILLAR1, Jose Victor de Sa Santos3, Murilo Jorge da Silva3, Victor Luis Peixoto Pereira Botelho3, Bianca Aparecida Colognese3, Marcio Andrade Barreto Filho4, Marcelo Vincenzo Sarno Filho3, Pollianna de Souza Roriz1 (1) Protocolo IAM - SAMU Salvador; (2) Hospital Ana Nery; (3) Universidade Federal da Bahia; (4) Escola Bahiana de Medicina e Saude Publica Introduction: The pandemic caused by the coronavirus that started in 2020 changed the pre-established dynamics in health systems and also in the user's itinerary in the search for medical care. Before, larger general hospitals shared the entrance of patients in the emergency network with pre-hospital units in a similar way. Objective: Identify possible changes in the itinerary of patients with Acute Myocardial Infarction with ST segment elevation (STEMI) in the urgency and emergency care network in the city of Salvador-BA. Methods: An ambispective study with patients with STEMI treated by the Acute Myocardial Infarction Protocol (AMIP) in Salvador during the pre-pandemic (Jan/2019 to Feb/2020) and pandemic (March/2020 to Dec/2021) period. The AMIP is a group designed to assist the entire process of care for patients with suspected STEMI, from diagnosis to reperfusion, in addition to training health professionals for management. Data were collected regarding the unit of origin: fixed pre-hospital (FPH) and general hospital (GH); assistance times; and mortality. Statistical significance was considered for p < 0.05. Results: In the pre-pandemic period, AMIP performed 542 attendings to STEMI, with 25.3% of access through GH. During the pandemic period, 935 visits to STEMI were performed, with the GH being the gateway in 12.0% of the calls (p < 0.001). During the pandemic, there was a higher frequency of activations through the FPH compared to the pre-pandemic period (76.3% x 61.4%; respectively; p < 0.001). Comparing the pandemic to pre-pandemic period, there was a shorter door-to-ECG time [33 (15-77) min x 38 (19-95) min, respectively; p = 0,04] and a shorter door-to-needle time [115 (80-180,5) min x 149 (101,8-206) min, respectively; p < 0,001] in the FPH access. Regarding GH entrance, comparing pandemic to pre-pandemic period, there was a lesser door-to-ECG time [28 (13,5-67) min x 44 (17-149) min, respectively; p = 0,01] and a lesser door-to-ballon time [221 (158,3-294,5) min x 297,5 (203,5-415,8) min, respectively; p = 0,049]. There was no difference in mortality between the groups (15.8% GH x 16.5% FPH; p = 0.92). Conclusion: After closure of general hospitals for non-COVID emergencies during the pandemic, there was a shift in the demand for medical care of patients with STEMI to the pre-hospital units, with shorter care times and without a major impact on mortality in our sample. 112061 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Access to High-Complexity Cardiac Technologies in the Brazilian Public Health System: A 12-Year Real-World Data Study on Cardiac Implantable Electronic Devices MIRIAM ALLEIN ZAGO MARCOLINO1, Miriam Allein Zago Marcolino1, Rodrigo Antonini Ribeiro2, Luis E. Rohde3, Carisi Anne Polanczyk4 (1) Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; (2) National Institute of Science and Technology for Health Technology Assessment - INCT/IATS (CNPq 465518/2014-1), Porto Alegre, Brazil; (3) Cardiology Center, Hospital Moinhos de Vento, Porto Alegre, Brazil; (4) Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Introduction: Cardiac implantable electronic devices (CIED) implantation and other high-complexity procedures in the Brazilian Public Health System (SUS) are restricted to tertiary care centers located in strategic geographic regions that should provide integral access to care with equity to all population. Objective(s): To describe geographic variations in the access to CIED implantation in the SUS over 12 years. Methods: A retrospective epidemiological study including open data of all hospital admissions with CIED implantation as primary procedure reimbursed by SUS from 2008 to 2019, obtained from the Hospital Information System of SUS Informatics Department (DATASUS). The mean annual rate per million (MM) population per region and state of residency was age and sex standardized by the OMS standard population. All analyses were performed using R. Results: SUS reimbursed 216,440 CIED implantations in the period (87.1/MM). Implantation rates varied according to residency region (South 124.9, Central-West 124.6, Southeast 86.7, Northeast 75.4, North 64.6/MM). The national distribution of different types of CIED implants showed distinct patterns of access by the residents of each state. Conclusions: Although the regionalization principle of SUS should ascertain equity in the access to health care, 12-year data reveal disparities in the access to different types of CIED in Brazil, showing the need of management actions on this field. 112098 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Heart Failure in North Region Brazil between 2017 and 2021 JOSE PEDRO DA SILVA SOUSA1, Jose Pedro da Silva Sousa1, Evaldo da Costa Sa Borges de Rezende2, Maria Eliza Alves Teixeira3, Juliana Leite de Oliveira2, Daniel Sorna Labeca Guerra2, Anna Luiza Alves de Oliveira Miranda1, Jose Wilker Gomes de Castro Junior1, Beatriz Siems Tholius1, Maria Eduarda dos Santos Lopes Vasconcelos1, Matheus Rocha Maia1 (1) Centro Universitario do Estado do Para; (2) Universidade Federal do Para; (3) Universidade de Gurupi Introduction: Heart failure (HF) is a syndrome that the main characteristic is the inability of heart to pump enough blood that the body's needs, due to damages in contraction and/or relaxation. Objective: Trace the epidemiological profile of HF patients in the Northern Region of Brazil between 2017 and 2021. Methods: Epidemiological, quantitative and observational study, with a retrospective design based on Health Unic System Informatical Department (DATASUS) data, through access to information on Epidemiology and Morbidity (SUS Hospital Morbidity) on HF from January 2017 to December 2021. Results: The age group with the highest number of hospitalizations, corresponding to 248,343 patients and 27.1% of hospitalizations in Brazil for HF, involved patients between 70 and 79 years of age. In relation to the region, there were 46,403 hospitalizations in the North of the country, with of these, 12,272 (26.4%) were patients between 70 and 79 years. In the analysis between sexes in the same region, the number of hospitalizations among men is higher (58.9% of hospitalized patients). When it comes to the mortality rate, the prevalence is among patients over 80 years old (17.64%) and the North region takes the second position with 12.30% of the total. In the analysis related to sex, in the North, the mortality rate is higher in females (12.97%). Conclusion: Data analysis corroborates the existence of an intrinsic relationship between advanced age and the hospitalization rate of patients with HF in the North region. This scenario is the result of the natural aging of individuals and the bad prognosis of the disease, which the survival rate is 35% after 5 years of diagnosis. In addition, it was observed that the North region ranks second among the Brazilian regions that have the highest mortality rate in patients over 80 years of age, which denotes inefficiency in the hospital management of this group. Furthermore, the study indicated a higher rate of hospitalization associated with men, due to their more negligent lifestyle in relation to health, but it identified higher mortality rates in females, which indicates less efficient therapeutic approaches for women in the management of HF. 112105 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Digital Interventions for Patients with Heart Failure and the Inequalities: Preliminary Analysis of the Egresos-IC Study EDMAR GERALDO RIBEIRO1, Lilian Cristina Rezende1, Julia Bicas Buback1, Tulio Batista Franco2, Deborah Carvalho Malta1, Luisa Campos Caldeira Brant1 (1) Universidade Federal de Minas Gerais UFMG; (2) Universidade Federal Fluminense UFF Introduction: Heart failure (HF) is the main cause of clinical hospitalizations for cardiovascular diseases in Brazil. Hospitalization for HF is related to adverse outcomes, including loss of quality of life, rehospitalizations and death. Digital health interventions (DHI) to improve cardiovascular care is an evolving field, with some studies showing a reduction in adverse outcomes in high-income countries. However, social disparities may be a barrier to the implementation of DHI in low resource settings, particularly due to lower access and education. Purpose: To compare the sociodemographic characteristics of patients discharged from hospital due to HF who refused or accepted to participate in a clinical trial that aims to evaluate the effectiveness of a DHI to improve HF care. Methods: In a randomized clinical trial with patients discharged from hospitalization for HF in a Brazilian capital city, 527 patients were screened in 6 months in 5 public hospitals, which accounted for 73% of hospitalizations for HF in the city. From these, 448 were not eligible, 54 refused to participate, and 79 participants were randomized in the study (43 in the intervention group and 36 in the control group). In a preliminary analysis, sex, age, race, marital status, education, and living in or outside the city were compared between those who refused or accepted to participate in the trial using Fischer's exact test. A p-value <0.05 was considered statistically significant. Results: Individuals who refused to participate in the study were older (69 vs. 62y, p < 0,001), less educated (53 vs. 30% with less than 4y of education, p = 0.007), with a greater proportion of individuals who self-reported their race as black/pardo compared to white (88 vs. 73%, p < 0.05), and lived more frequently outside the capital city (36 vs. 20%, p < 0.05) than those who accepted. There was no difference between the proportion of females or marital status between the groups. Conclusions: DHI have the potential to overcome major barriers in HF care, such as: access to GDMT care, treatment adherence, and health education. However, our results show that among the eligible population, the most socially vulnerable individuals refused to participate in the trial. As such, DHI studies must evaluate and address the barriers for the acceptance of the intervention to guarantee that DHI in HF care do not increase inequalities. 112108 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Temporal Trends in Cardiac Electronic Implantable Devices Implantation in the Brazilian Public Health System: A 12-Year Real-World Data Study MIRIAM ALLEIN ZAGO MARCOLINO1, Rodrigo Antonini Ribeiro2, Luis E. Rohde3, Carisi Anne Polanczyk4 (1) Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; (2) National Institute of Science and Technology for Health Technology Assessment - INCT/IATS (CNPq 465518/2014-1), Porto Alegre, Brazil; (3) Cardiology Center, Hospital Moinhos de Vento, Porto Alegre, Brazil; (4) Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Introduction: Cardiac implantable electronic devices (CIED) are technologies long available in the Brazilian Public Health System (SUS). The aging population and increased incidence and prevalence of cardiovascular diseases can impact the rates of CIED implantation, which are essential information for health policy strategies. Objective(s): To describe the temporal trend of CIED implantation in the SUS before the pandemic, according to devices and patient characteristics. Methods: A retrospective epidemiological study including open data of all hospital admissions with CIED implantation as a primary procedure reimbursed by the SUS between 2008 and 2019, obtained from the Hospital Information System of the SUS Informatics Department (DATASUS). The annual rate per million (MM) population per CIED type was age and sex standardized by the OMS standard population. All analyses were performed using R. Results: In the period, 216,440 CIED implants were reimbursed by SUS, with a mean annual rate of 87.1/MM, mostly pacemakers (78.1/MM). Despite the growing number of implants per year, from 14.403 to 20.635 (+43.2%), CIED implantation rate reduced from 92.8 in 2008, to 83.7/MM in 2019 (-9.7%), mainly due to the reduction of pacemaker implants (-12.3%). Cardiac resynchronization therapy (CRT) decreased 57% from 2008 to 2019 (3.55 to 1.53/MM), while CRT with defibrillator implantation increased 3.5 times (0.82 to 2.87/million) and implantable cardioverter-defibrillator (ICD) increased 30%. . Conclusions: There was a decrease in the implantation rates of CIED in SUS, mainly derived from a decrease in the implantation of pacemakers and CRT. The decrease in the implantation rates may be due to an unbalance between the populational growth and the increase of these technologies' access in the period. Moreover, implantation of CRT with a defibrillator and ICD increased in the observed period, in accordance with contemporary guidelines. 112119 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR SURGERY Study of the Prevalence of Functional Alterations in the Postoperative Period of Cardiac Surgeries According to the International Classification of Functioning, Disability and Health (ICF) MICAELE FARIAS NASCIMENTO1, Beatriz Souza de Albuquerque Cacique New York1, Milton Antonio Goncalves de Oliveira1, Katia Elizabete Galdino1, Ana Tereza do Nascimento Sales Figueiredo Fernandes1 (1) State University of Paraiba - UEPB Introduction: Functional changes can now be assessed in a more complete and reliable way through the International Classification of Functioning, Disability and Health (ICF), created by the World Health Organization (WHO), improving communication between interested people and health professionals and bringing an important facility for international comparisons. Objective: To investigate the prevalence of functional changes in the postoperative period of cardiac surgeries based on the ICF codes. Methods: Cross-sectional study, where 100 patients undergoing reconstructive cardiac surgery (coronary artery bypass grafting and valve repair), replacement (valve replacement) and correction (correction of congenital heart diseases) in a public referral hospital in Cardiology were evaluated, with prior permission from the patient regarding the use of their postoperative data. The functional alterations present were evaluated through the ICF, according to the 8 chapters of the Body Functions Component. The data computed through the form used were collected, quantified and presented through means, standard deviation and percentages. Results: The mean age was 59.2 +- 12.3 years. Changes in sensory and pain functions (96%) were the most present postoperatively, followed by functional changes in the cardiovascular system, hematological and immune systems, and respiratory system (31%), mental functions (17%), functions of the digestive system and metabolic and endocrine systems (5%), neuromusculoskeletal and movement-related functions (4%), and changes in genitourinary and reproductive functions (3%). No alteration of voice and speech functions (Chapter 3) was presented in the study patients. Chest pain after the surgical procedure was reported by 98% of the patients, being justified mainly by the sternotomy process performed in cardiac surgeries. Conclusion: Cardiac surgeries have several organic repercussions that can alter physiological mechanisms and may lead to a critical postoperative state, implying the need to reinforce evaluation methods and intensive care in order to establish a good recovery for patients. 112148 Modality: E-Poster Young Researcher - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Spontaneous Coronary Artery Dissection. Initial Experience of the Brazilian Scalibur Registry PAULA SANTIAGO TEIXEIRA2, Julio Paiva2, Alessandra Oliveira2, Carlos Campos3, J. Ribamar Costa3, Henrique B Ribeiro2, Milena Fonseca1, Barbara Freitas1, Jamil Cade1, Breno O. Almeida1, Adriano Caixeta1 (1) HOSPITAL ISRAELITA ALBERT EINSTEIN; (2) UNIVERSIDADE FEDERAL DE SAO PAULO; (3) INSTITUTO DO CORACAO DO HCFMUSP Background: Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic, traumatic or iatrogenic epicardial dissection. The pathophysiology is not yet fully elucidated, but is related to triggering factors such as emotional stress, physical stress, or pregnancy. It occurs by intramural hematoma formation or intimal rupture that obstructs the coronary artery, causing acute myocardial infarction, especially in young women (<50 years). Demographic, clinical and angiographic description of SCAD in a Brazilian cohort is poorly explored. Objective: To evaluate the demographic, clinical, angiographic profile and triggers of SCAD in a Brazilian population. Methods: The SCALIBUR registry is a retrospective and prospective study of patients with SCAD involving 22 Hospitals in Brazil. REDcap database review in the period 2010-2022. Results: There were 183 patients with SCAD, with a mean age of 50.15 +- 10.56 years (29 to 84 years) with prevalent incidence in female gender (85%). Patients had none or few risk factors for coronary artery disease, including hypertension (6%), family history of early coronary artery disease (22.5%), mixed dyslipidemia (5%), and active smoking (18%). Ten percent of SCAD cases occurred in the gravid-puerperal cycle. Most cases of SCAD manifested as acute myocardial infarction without supra-ST, NSTEMI (45%), acute myocardial infarction with supra-ST, STEMI (34%), and unstable angina (9%). Among the triggering factors, present in 57.8% of the cases, emotional stress (21%) and menopause (16%) stand out. Fibromuscular dysplasia, not systematically investigated, was observed in a few cases (7%), pregnancy (0.5%), puerperium (9%), physical stressor (5.4%), use of hormone therapy (3%) and psychiatric diseases (2.7%). The anterior descending artery was the most affected vessel, followed by the right coronary and circumflex arteries. SCAD type II occurred in (48.82%). Most frequent serious complications were cardiogenic shock (3.27%) and cardiac arrest (1%). Conclusion: In this large Brazilian cohort, SCAD affected mostly young women with no or few classical risk factors for coronary heart disease and the predominant trigger was emotional stress. It is an underdiagnosed condition, but should be considered in the differential diagnosis of acute myocardial infarction in young women. Demographic and angiographic findings seems to be similar to other ethnicities including in the United States, Canada and Europe. 112149 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Identification of a Novel Pathogenic Variant in FBN1 Associated with Marfan Syndrome JULIANA DA ROCHA FERREIRA1, Juliana da Rocha Ferreira1, Julia Passarelli Pereira1, Anna Paula Arpini Botelho1, Marcelo Machado Melo1, Glauber Monteiro Dias2 (1) Instituto Nacional de Cardiologia - INC; (2) Universidade Estadual do Norte Fluminense Darcy Ribeiro - UENF Aortic diseases arising in Marfan Syndrome (MFS), such as in aneurysms and dissections of the thoracic aorta, are related to genetic alterations in the FBN1 gene. Databases, such as Universal Mutations-FBN1, ClinVar and The Human Gene Mutation, contain more than a thousand FBN1 mutations associated with MFS. The FBN1 gene, which encodes fibrillin-1, is responsible for the integral production of different protein domains. Possible genetic changes may lead to a weakening of blood vessels, leading to the development of aortopathies. In this study, we present the association of a novel FBN1 variant with MFS. The proband is a man who presented ascending aortic aneurysm and dissection (TAAD) at 42-yr-old, which was surgically treated. Clinical investigations were performed in all family members enrolled in the study. Marfan signs were observed in the proband, daughters and granddaughter. Direct sequencing of the FBN1 gene in the proband identified a novel truncation variant p.(Glu2019Ter) and a cascade screening were done. The variant was classified as pathogenic and causal for MFS according to the American College of Medical Genetics and Genomics (ACMG) criteria and revised Ghent nosology for MFS diagnosis, respectively. Proband's daughter and granddaughter harbor the variant, however without aortic alteration. This work reports for the first time a patient with the FBN1-p.(Glu2019Ter) variant and its association with MFS/TAAD. 112121 Modality: E-Poster Young Researcher - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Angiographic Findings in Heart Transplant Patients and Their Correlation with Survival JOAO GABRIEL GUEDES DA CUNHA MELLO1, Joao Gabriel Guedes da Cunha Mello1, Santiago Raul Arrieta1, Pedro Alves Lemos Neto1, Marcelo Biscegli Jatene1, Cauyna Gurgel Moreira1, Estela Azeka1 (1) Instituto do Coracao/InCor Introduction: Heart transplantation is an effective option for the treatment of end-stage heart failure. Cardiac allograft vasculopathy (CAV) is considered one of the leading causes of long-term mortality in these patients. The objective of this study is to evaluate the type of angiographic lesions and the impact of CAV on the survival of heart transplant recipients at a referral center. Methods: Retrospective cohort of cineangiography between 2013 and 2022 in patients that underwent heart transplantation. Demographic, clinical and examination data were obtained from medical records as well as the institutional database. Results: The number of transplanted patients during the period of the study was 196, and coronary angiography was performed in 130 (66.3%) of them. Of these (n = 130), 65 (50%) were males, the median age at transplantation was 9.6 +- 7.8 years, and the median age at diagnosis of the first lesion was 6.2 years. CAV was observed in 29 of them (22.3%). The affected arteries followed the given profile: left anterior descending (LAD) 30.9%, right coronary 16.9%, marginal 14.1%, circumflex 12.7%, posterior descending and posterior ventricular 12.7%, diagonal 8.5% and left main coronary artery 4.2%. The CAV classified as moderate and severe were the most common (37.9% each). The event-free survival curve in transplant patients with CAV shows significant sequential drops in 10 years of transplantation, when compared to the curve for patients without CAV (log-rank p = 0.0001). Other coronary angiographic findings correspond to 11.6% of the total of exams, which were, coronary-cavitary fistulas, pulmonary artery fistulas, mediastinal venous plexus fistulas, myocardial bridges, single ostium coronary artery, anomalous origin of coronary artery and thrombi. Conclusions: A prevalence of 22.3% of CAV was observed in transplanted patients that underwent coronary angiography. Moderate and severe lesions were the most common, and the LAD artery was the most affected. CAV has a major negative impact on event-free survival in transplant recipients. 112131 Modality: E-Poster Young Researcher - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Contribution of Cardiovascular Risk Factors to Non-Ischemic Left Ventricular Systolic Dysfunction in Patients Referred to Myocardial Perfusion Imaging MARIA EDUARDA KOSTECKI1, Wilson Nadruz Junior2, Odilson Marcos Silvestre3, Ramon Conde4, Daniel Macedo4, Ana Carolina de Franca5, Giulia Caldeira Gaelzer5, Mariana De Nadai Andreoli4, Carlos Cunha6, Rodrigo Julio Cerci6, Joao Vicente Vitola6, Miguel Morita Fernandes-Silva6 (1) Hospital Santa Casa de Misericordia de Curitiba (HSC); (2) Universidade Estadual de Campinas (Unicamp); (3) Universidade Federal do Acre (UFAC); (4) Universidade Federal do Parana (UFPR); (5) Pontificia Universidade Catolica do Parana (PUCPR); (6) Quanta Diagnostico por Imagem (QDI) Background: Cardiovascular risk factors (RF) can lead to left ventricular (LV) remodeling, regardless of the presence of coronary artery disease (CAD). The contribution of each RF to non-ischemic LV dysfunction in the population is uncertain. Aim: To estimate the proportion of non-ischemic LV systolic dysfunction attributable to each CV risk factor in patients undergoing myocardial perfusion imaging (MPI). Methods: This is a cross-sectional study of patients undergoing MPI in an imaging center in Curitiba, Brazil, from 2010 to 2021. We excluded those with known previous coronary artery disease or any perfusion myocardial defects at MPI. Data on traditional CV risk factor, including hypertension, diabetes mellitus, and smoking status, were obtained during medical history before MPI exam. Obesity was defined as body mass index >=30 Kg/m2. LV dysfunction was defined as LV ejection fraction below 50% from rest gated-SPECT. The population attributable fraction (PAF) for LV dysfunction was estimated for each CV risk factor. Results: We evaluated 28,156 patients (60 +- 12 years old, 51% women), 632 (2%) having VL dysfunction. After adjusting for age, sex and body mass index, hypertension (adjusted Odds Ratio [95% Confidence Interval]: 1.34 [1.12, 1.60]), diabetes mellitus (adj OR: 1.43; 95%CI 1.18, 1.74) and smoking (adj OR: 1.69; 95%CI 1.35, 2.13) were independently associated with LV dysfunction, but obesity was not (adj OR: 0.89; 95%CI 0.68, 1.17). Hypertension had the highest PAF for LV dysfunction, followed by diabetes mellitus and smoking. Conclusion: In this large study of patients referred to MPI, hypertension and diabetes mellitus were the CV risk factors that mostly contributed to non-ischemic LV dysfunction in the population, followed by smoking status. 112158 Modality: E-Poster Young Researcher - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Coronary Artery Calcification as Risk Factor for Intensive Care Unit Admission Among Adults with COVID-19 GABRIELE CARRA FORTE1, Cristina Carra Forte1, Rubens Gabriel Feijo Andrade1, Luis Miguel Millan Diaz1, Bruno Hochhegger1 (1) Pontificia Universidade Catolica do Rio Grande do Sul - PUCRS Background: Severe acute respiratory syndrome coronavirus 2 is recognized as a multisystemic disease. Clinical studies have reported a complex interplay between cardiovascular disease and worse outcomes in COVID-19 patients. Purpose: To evaluate the association between coronary artery calcification (CAC) and intensive care unit admission among COVID-19 patients. Methods: This is a retrospective cohort study design. All eligible patients underwent a chest CT scan, who were admitted in tertiary university hospital, at the first wave from April 01 until December 31, 2020, were included. A positive COVID-19 case was defined as one polymerase chain reaction test positive for COVID-19. Clinical outcomes were collected from electronic medical records. CAC was graded with a semiquantitative grading system and classified as 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. All data were rated in consensus by 2 readers. The readers were blinded for patient outcomes. Results: 441 consecutively admitted COVID-19 patients were included. Among them, 159 (36.4%) had coronary calcification: 80 (18.3%) patients classified as mild degree, 73 (16.7%), as moderate and six (1.4%) as severe. Sixty-four (14.5%) required admission to an intensive care unit; and 54.7% of these required invasive mechanical ventilation. The presence of CAC was associated with intensive care unit admission (OR 4.37, 95%CI 2.46-7.74, p < 0.001), adjusted for multiple confounders. Conclusion: Estimated risks for intensive care unit admission were consistently higher for patients with COVID-19 and coronary artery calcification. In addition, including CAC standard chest CT for these patients may help guide clinical decision and prognosis. 112161 Modality: E-Poster Young Researcher - Non-case Report Category: NURSING Impact of Telemonitoring as a Care Tool in Patients with Heart Failure: Integrative Review NICHOLLAS COSTA ROSA1, Brenda Goncalves Donay Alves1, Melissa Schiwe1 (1) Centro Univeristario Ritter dos Reis Introduction: Heart failure (HF) is the final pathway of most heart diseases, it has a great impact on the quality of life of patients with this condition, due to progressive symptoms. Telemonitoring of patients with HF aims to reduce hospitalizations, mortality and improve quality of life. Objective: To identify the impact of telemonitoring as a care tool in patients with HF. Method: This study is an integrative review. The bibliographic search was carried out from August to October 2021. The combination of the following descriptors in health sciences (DeCS) was used as a search strategy: "Telemonitoring" and "Heart failure" crossed using the Boolean connector AND or OR. Randomized clinical trials articles were included, indexed in the aforementioned databases in the last 5 years (2016 to 2021). Results: The search resulted in 285 articles, from the reading of the title and abstract, 60 publications were selected, after reading in full, the final sample consisted of 12 articles. The study by Feijo et al. 2021, had 206 randomized patients and demonstrated that the use of a diuretic adjustment algorithm improves the combined outcome in these outpatients, demonstrating a reduction in HF admissions and clinical instability. The studies by Koehler et al. 2021 and Kalter Leibovici et al. (2017), randomized 710 and 1360 patients respectively, demonstrated that care improved depressive symptoms and had a positive influence on quality of life in patients with HF and moderate depression. The study by Winkler et al. 2021, obtained 1119 randomized patients, as a result obtained a reduction in unplanned hospitalizations and emergency calls could be considered a marker of higher morbidity and mortality. Galinier et al. (2020) and Frederix et al. (2018), randomized 937 and 160 patients respectively, telemonitoring did not result in a significantly lower rate of all-cause deaths or unplanned hospitalizations in patients with HF, but in the study of there was a significant reduction in the number of days of hospitalization for HF. Conclusion: Telemonitoring is a tool that has great potential to improve self-care regardless of the patient's clinic, however, impacts on readmissions and mortality were not a consensus in all studies. This can be attributed to the different ways of applying telemonitoring and different audiences addressed in each study. 112173 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION Correlation of In-Hospital Mortality in Elderly Patients and Those with Prolonged Hospital Stays between Clinical and Surgical Inpatients Recently Diagnosed with Venous Thromboembolic Disease BERNARDO CLETO TELES E SILVA1, Lara Camporez Menezes Trindade1, Priscila Diaz1, Antonio Amaral1, Ana Pedroso1, Joao Reis1, Flavia Moises1, Alessandra Godomiczer1, Monica Amorim1, Claudio Carvalho1, Thaisa Garcia1, Andrea Haddad1 (1) Unimed Rio Goals: To evaluate data from patients who had thromboembolic events during hospital stay from Jan 2020 to Mar 2021, correlating length of stay and age with in-hospital mortality in a private quaternary hospital. Methods: Retrospective cohort where consecutive patients admitted to a private quaternary hospital from January 2020 to March 2021 were evaluated, for clinical and surgical hospitalization for at least 48 h. All were evaluated according to risk stratification for VTE by the physician and prophylaxis instituted according to the risk found. Patients admitted with DVT and/or PE, arterial thrombosis events and those in palliative care were excluded from the analysis. DVT (distal and proximal), device thrombosis (PICC and AVP) and PE events were recorded. These outcomes were confirmed with EchoDoppler imaging. Results: We correlated data on thromboembolic events with length of stay and age with an increased risk of in-hospital mortality. In the described period, there were 126 events, of which 120 (92.5%) were DVT and 6 (4.8%). The mean age was 70.8 +- 12.3 years. The age group distribution is shown in table 1. 74 of the patients (58.7%) were male and the mean BMI was 29.6 +- 6.4 kg/m2. The most common risk factors were age >65 years (89.7%), immobility or bedridden (49.2%), neoplasia (13.6%) and surgery or trauma (11.1%). Among patients who had VTE during hospitalization, 63.5% were hospitalized due to COVID-19 infection (figure 1), 35% remained hospitalized for 7-29 days (Graph 1) and 49 patients (38.9%) died. A total of 78.5% were hospitalized for >7 days. 48 patients died, of which 60.3% had more than 7 days of hospitalization among patients who had VTE. There is a correlation between length of hospital stay and higher risk of VTE and mortality, especially in patients with COVID19. Conclusao: VTE is a frequent condition in hospitalized patients and is related to longer hospital stay, as well as advanced age with in-hospital mortality. COVID-19 caused patients to stay in hospital longer, which increased the frequency of VTE. 112193 Modality: E-Poster Young Researcher - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hospitalization and Death Secondary to Different Circulatory System Diseases between 2015-2021: A Brazilian National Database Analysis GIOVANNA LIDIA GONDIM OLIVEIRA DIAS1, Paulo Carvalho Ximenes de Aragao Filho1, Joaquim Francisco Cavalcante Neto1, Mateus de Sousa Cavalcante1, Leandro Cordeiro Portela1, Lucas Almeida Magalhaes1 (1) Federal University of Ceara Introduction: Cardiovascular diseases are the most prevalent comorbidities worldwide and one of the main causes of hospital admissions and mortality, including in Brazil. It is essential to identify the most common conditions in this morbidity group and to guide populations on how to prevent the development of these diseases and their respective negative outcomes. Methods: This is a descriptive, cross-sectional, prevalence study retrospective in nature. The objective is to compare the number of hospitalizations and deaths in Brazil among the main diseases of the cardiovascular system, between 2015-2021. The data used for this work came from DATASUS, in a public electronic data platform of the Brazilian government named "TabNet". The following informations were consecutively selected: "Epidemiology and Morbidity", "Hospital Morbidity on SUS (SIS/SUS)", "General, by hospitalization site - from 2008", and "Brazil by regions". The line for table it is classified by "ICD-10 Morb List", in the column has been selected "Year of attendance" and in the content has been placed "Admissions", "Deaths" and "Mortality Rate". The period settled was between "January 2015" and "December 2021". Results: In Brazil, between 2015-2021, the number of hospitalizations due to circulatory system diseases was 7,714,326, of which 667,815 patients died. Among these hospitalizations, 1,374,104 were due to heart failure - with 156,484 deaths; 1,082,705 due to stroke (ischemic or hemorrhagic) - with 169,224 deaths; 841,559 due to acute myocardial infarction - with 87,432 deaths; 1,017,709 from other ischemic heart diseases - with 27,162 deaths; 457,861 due to varicose veins of the lower limbs - with 1,707 deaths; 440,936 due to conduction disorders and cardiac arrhythmias - with 52,139 deaths; and other morbidities with fewer hospitalizations. Discussion: Analyzing the results presented, the impact of cardiovascular diseases on the public health system is undeniable. Annually, it corresponds to a large number of hospital admissions in Brazil. The comorbidity that caused the highest number of hospitalizations in the last six years was heart failure, followed by stroke. However, stroke has the highest gross number of deaths and the highest mortality rate. In addition, not all diseases with high hospitalization evolve with a significant number of deaths, such as varicose veins of the lower extremities and other ischemic heart diseases (except acute myocardial infarct). 112220 Modality: E-Poster Young Researcher - Non-case Report Category: PHYSIOTHERAPY Comparison between Face-to-Face Rehabilitation and Cardiopulmonary Telerehabilitation in Post Covid KAMYLLA MARIA ALCANTARA SILVA ALVES1, Kamylla Maria Alcantara Silva Alves1, Ana Eugenia Vasconcelos do Rego Barros1, Bruna Thays Santana de Araujo1, Talyta Oliveira de Almeida1, Daniella Cunha Brandao1 (1) UFPE The pandemic caused by the SARS-Cov-2 virus brought several new challenges in the health area, among them, in the lives of patients, generating a decrease in functional capacity and an increase in the fatigue of patients who contracted the disease, having a direct impact However, as in the context of the current pandemic, the recommendation is to maintain as much social isolation as possible, telerehabilitation has proved to be an alternative resource to help improve the functional capacity of these patients and improve their quality of life. Objective: To compare the effectiveness of face-to-face rehabilitation (PR) and telerehabilitation in relation to quality of life, intensity and impact of fatigue in post-COVID-19 patients. Methods: Patients with a history of hospitalization for COVID-19 were allocated to the face-to-face rehabilitation group, whereas those who were not hospitalized were allocated to the telerehabilitation group. the activities of daily life and, consequently, in the quality of life. Thus, cardiopulmonary rehabilitation has been shown to be of great relevance and efficiency in the recovery of such patients. All participants answered the Medical Outcomes Study Short - Form 36 questionnaire and the Fatigue Pictogram. PR was performed and telerehabilitation was performed via the online platform google meet, during 12 sessions, twice a week. The intervention protocol consisted of flexibility, aerobic, strengthening and breathing exercises. This work is an experimental study with a non-probabilistic sample. Results: 12 patients in each group completed rehabilitation, totaling 24 patients. The mean age was 42.83 +- 14.45 years for the telerehabilitation group and 47.67 +- 10.83 years for the PR group. There was an improvement in quality of life in all domains of the SF-36, both in the telerehabilitation group, with a total score of 267.08 +- 125.50 vs 453 +- 186.03 (p < 0.01), and in the RP group. 298.38 +- 205.61 vs 470.31 +- 142.09 (p < 0.01) with no difference between the groups. Regarding fatigue, a reduction of 66.66% and 100% in the "very tired" category was observed for the telerehabilitation and RP groups, respectively. And the reduction in the impact of fatigue was observed by the greater number of individuals who reported being able to "do almost everything". Conclusion: It was observed that both face-to-face rehabilitation and telerehabilitation are capable of promoting an improvement in quality of of life, with no differences between them. 112221 Modality: E-Poster Young Researcher - Non-case Report Category: CARDIOVASCULAR IMAGING Thoracic Aorta Calcification and Mortality in COVID-19 Patients GABRIELE CARRA FORTE1, Cristina Carra Forte1, Rubens Gabriel Feijo Andrade1, Luis Miguel Millan Diaz1, Bruno Hochhegger1 (1) Pontificia Universidade Catolica do Rio Grande do Sul - PUCRS Introduction: Coronavirus disease 2019 had a great impact worldwide, being an important cause of morbidity and mortality in several countries. Although the typical clinical presentation is acute respiratory syndrome, cardiovascular disease is frequent and reported as an important determinant of poor clinical outcome. Purpose: To evaluate the association of thoracic aorta calcification on in-hospital mortality in COVID-19 patients. Methods: All patients with SARS-CoV-2 infection, who underwent a chest computed tomography (CT) in a tertiary university hospital in southern Brazil, between April and December 2020 were prospectively included. Clinical outcomes were collected from electronic medical records. Thoracic aorta calcification, body composition and bone mineral density was evaluated by low-dose chest computed tomography imaging (chest CT scan), widely performed in moderate to severe SARS-CoV-2 patients. Patients were classified as without calcification (0), having mild calcification (1), moderate (2) or having severe (3) calcification. The readers were blinded for patient outcomes. Results: In all, 441 patients were enrolled in the study. There was a predominance of females (54%), and the mean age was 55 +- 19.2 years. Visceral and subcutaneous fat area was 116.9 m2 (55.4-174.0) and 115.3 m2 (67.0-181.1), respectively, and muscular area was 102.5 m2 (84.2-126.8). The bone mineral density was 171.5 (120.0-219.0)HU. After adjustment for covariates, thoracic aorta calcification [OR 11.45 (95%CI 1.745-75.194); p < 0.001], mechanical ventilation [OR 25.45 (95%CI 3.542-182.972); p < 0.001), visceral fat area [OR 1.01 (95%CI 1.003-1.023); p = 0.014] resulted to be independent predictors of in-hospital mortality. Conclusion: Mechanical ventilation, thoracic aortic calcification and visceral fat area permits to stratify the COVID-19 patients in-hospital mortality risk. In addition, to include the thoracic aorta calcification evaluation on standard chest CT for these patients may help guide prognosis and clinical decision. 112228 Modality: E-Poster Young Researcher - Non-case Report Category: ANTICOAGULATION Use of Direct Oral Anticoagulants (DOACs) in the Postoperative Period of Femur Fracture After Hospital Discharge as Prophylaxis for Venous Thromboembolism ANA CAROLINA PEDROSO1, Ana Carolina Pedroso1, Monica Amorim1 (1) Unimed rio hospital Patients with femoral neck fractures have an increased mortality rate. Femoral neck fracture is frequently found in women over 60 years of age and its incidence has been increasing in many parts of the world due to the increase in life expectancy in this age group. Total hip arthroplasty (THA) is one of the most successful surgical procedures in the field of orthopedic surgery. Oral anticoagulants are indicated in the postoperative period (PO) of hip arthroplasty to prevent thromboembolic events. Direct oral anticoagulants (DOACs) were considered by studies to be effective in preventing thromboembolic events, as was enoxaparin. goal Ensure the use of anticoagulant in patients discharged from hospital in the PO of femur fracture, as prophylaxis for venous thromboembolism. Methods: Retrospective cohort from Jan 2019 to Dec 2021 in hospitalized patients with a diagnosis of femur fracture undergoing hip arthroplasty surgery. In a total of 34,167 patients, 373 patients were admitted with a femoral fracture, 28 patients died during hospitalization, and were considered to be patients aged >60 years. All patients were evaluated according to risk stratification for VTE by the physician and prophylaxis was instituted according to the risk found. All patients in the PO period of hip arthroplasty are considered high-risk patients. Results: Of the 34,167 hospitalized patients, 1.1% were due to femoral fractures, of which 7% died during the hospitalization period. Follow-up was performed for 30 days. Of the 345 patients who were discharged from hospital, 100% received anticoagulation with enoxaparin or rivaroxaban or apixaban. Conclusion: Anticoagulation is safe and effective in prophylaxis of thromboembolic events in the postoperative period of femur fracture, showing no risk of increased bleeding with the use of DOACs. Despite the reduced follow-up time of these patients, there was no readmission for VTE. 108565 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Emergent Aortic Balloon Valvuloplasty on a Cardiogenic Shock Patient: A Case Report JOAO MIGUEL MARTINS DE CARVALHO1, Tania Proenca1, Ricardo Alves Pinto1, Joao Carlos Silva1, Filipe Macedo1 (1) Centro Hospitalar Universitario Sao Joao (CHUSJ), Porto, Portugal Severe aortic stenosis patients who are critically ill are in high risk for mortality. Aortic balloon valvuloplasty (ABV) can be done on emergency, improving hemodynamic status on short-term and can be life-saving. A 59 years old male, with known medical history of hypertension, diabetes, renal cell carcinoma treated with parcial right nephrectomy, had severe aortic stenosis, severe left ventricle dysfunction (left ventricle ejection fraction [LVEF] 15%) and 3 vessel coronary artery disease (50% stenosis on the medium segment of the left anterior descending [LAD], 90% stenosis on the proximal segment of the circumflex, 90% stenosis in the proximal right coronary artery, followed by a occlusion on the middle segment; the distal vessels were in good condition) was awaiting surgery when he was admitted to the Internal Medicine ward on January 2019 with a respiratory infection with hypoxemia and severe systemic inflammatory response syndrome. On the same day, he presented with an inferior ST elevation myocardial infarct and cardiogenic shock. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) and aminergic support were initiated and he was submitted to emergent coronary angiography that revealed progression of the LAD disease, with 90% stenosis on the medium segment. It was decided in Heart Team to perform an emergent ABV; the mean left ventricle-aortic gradient reduced to 10 mmHg. It was decided not to perform LAD angioplasty due to the high procedure risk and the probable need for surgical treatment soon. A week later, the patient was submited to surgery with VA-ECMO support, having performed a coronary artery bypass graft with the left internal mammary artery to the LAD; he didn't perform aortic valve replacement surgery due to highly calcified aortic root. On the 8th day pos-op, the patient presented with a hemopericardium and tamponade, needing to be submitted to a new surgery. He was off VA-ECMO and aminergic support by day 12 pos-op. On the 21st day pos-op, the patient was submitted to transcatheter aortic valve implantation (TAVI). The pos-procedure echocardiogram showed a normofunctional aortic prothesis and an improvement in LVEF (36%). The patient was discharged, remaining during follow-up in NYHA functional class I. ABV can be a bridge to TAVI or surgery in highly unstable patients, contributing to patient stabilization. It can be done on an emergency basis, can alter the patient prognosis and should be considered in these patients. 108006 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Disulfiram-Ethanol Reaction Causing the Deadly Shark Fin Electrocardiogram Pattern ANDRE FILIPE MACEDO ALEXANDRE1, Dias de Frias1, Andreia Campinas1, Joao Silveira1, Severo Torres1 (1) Centro Hospitalar Universitario do Porto, Porto, Portugal Disulfiram is used for the treatment of chronic alcoholism. Yet, it is not a safe drug in patients who still drink alcohol due to disulfiram-ethanol reaction (DER). Acute myocardial infarction due to DER has been rarely reported, and most reports suggest coronary vasospasm as the causative mechanism. We present a case of myocardial infarction probably due to DER, in which "white thrombus" formation was found instead of vasospasm. This 65-year-old man with history of schizophrenia and chronic alcoholism was admitted for out-of-hospital cardiac arrest. After 10 minutes of advanced cardiac life support with four defibrillation shocks, the patient returned to spontaneous circulation and the ECG revealed an anterior "shark fin" STEMI. The patient was referred for emergent coronary angiography, which revealed acute thrombotic occlusion of the left anterior descending artery. Aspiration thrombectomy was performed with recovery of a large "white thrombus", and a drug-eluting stent was implanted. This patient has been prescribed disulfiram the week before STEMI presentation, yet he was still drinking alcohol while taking the drug. We suspect that DER may have been responsible for plaque instability due to close temporal relationship. This clinical case highlights that DER can not only cause myocardial ischemia by coronary vasospasm, but can also predispose to thrombus formation, leading to extensive myocardial infarction. 108133 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Myocardial Infarction with Aortic Dissection in the Puerperium: Case Report FRANCIELLY DOS SANTOS VIEIRA1, Marina Vitoria Silva Costa1, Nathalia Abdo Zuliani1, Jessica Evangelista de Queiroz1, Leonardo Teixeira de Melo1 (1) Universidade Federal de Uberlandia - UFU Preface: Cardiovascular diseases are an important cause of gestational and puerperal morbidity and mortality. Because it is rare, aortic dissection is difficult to diagnose during pregnancy and the puerperal period, contributing significantly to maternal mortality due to its high fatality rate, comprising 4% of the causes of maternal death. Case Report: A 38-year-old primiparous patient, on the fifth day of the puerperium (cesarean section), with left renal agenesis, without other gestational comorbidities or complications, presented with severe chest pain with irradiation to the back, upper limbs, neck and jaw. She immediately sought tertiary care, where she was admitted for dyspnea, sweating, bradycardia, and hypotensiveness. Electrocardiogram suggestive of acute myocardial infarction with inferior wall ST elevation. She was referred for coronary angiography, which showed type A aorta dissection associated with acute occlusion of the right coronary artery and right renal artery, without occlusion of supraaortic or mesenteric vessels. She underwent stent implantation in the right coronary artery, followed by emergency surgery with replacement of the ascending aorta using a number 28 Dacron tube and replacement of the aortic valve with a Carpentier Edwards biological prosthesis number 23, replantation of the left coronary artery (Bentall de Bono surgery), associated with implantation of a saphenous vein bypass for the right coronary artery. She remained in the intensive care unit for six days for hemodynamic reestablishment, being discharged on the 11th postoperative day without major complications. Conclusion: Aortic dissection is a rare, life-threatening condition for two main reasons: increased risk of aortic rupture and compromised blood flow from the systemic circulation to major organs by occlusion of the arterial lumen. Pregnancy is one of the main risk factors for arterial dissection among young women. Approximately 60% of them occur related to pregnancy and puerperium, being the third cause of maternal death related to cardiovascular diseases. The therapeutic approach does not differ much from that proposed for other patients, and emergency surgery to replace the ascending aorta with a Dacron tube is the best option in cases of type A acute dissection. 110102 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Subclavian and Right Common Carotid Stenosis by Vascular Kinking in a Patient with Symptoms of Transient Ischemic Attack in the Emergency Room - a Case Report LAIS ANTONUCCI FERREIRA1, Katia Gleicielly Frigotto1, Washington Luiz Batista da Costa1, Daniela Roberta Alves Silva1, Luciano de Figueiredo Aguiar1 (1) Hospital Sao Lucas Copacabana Introduction: Kinking artery is an angular alteration that forms a sharp angle in an artery. Embryogenic and acquired causes can lead to this alteration. Congenital factors are clinically significant in older age, aggravated by arterial hypertension (AH), diabetes mellitus (DM), dyslipidemia, smoking, rheumatological and heart diseases. This alteration is more common in the internal carotid artery, but is rare in subclavian and common carotid arteries. That condition is often asymptomatic, but can present neurologic symptoms, such as mimicking a transient ischemic attack (TIA) due artery stenosis. Diagnostic investigations can be made by anamnestic and clinical data, doppler ultrasonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). The therapeutic includes anti-aggregation and anticoagulation therapy, antihypertensives, antilipidemic, cerebral vasodilatation therapy, and surgical treatment if indicated. Case description: The 77-year-old female patient was admitted to the Emergency Room, due dysarthria and loss of upper body strength, with spontaneous improvement in approximately 15 minutes. She has been reported to have diagnosis of HAS, DM, dyslipidemia, parkinson disease, and previous TIA. In the neurological examination she was conscious and disoriented, presenting miosis and ptosis on the right side, without strength deficit. CTA indicated kinking in the right subclavian and common carotid arteries. The patient was treated with acetylsalic acid, clopidogrel, atorvastatin, antihypertensive and antidiabetic therapy. Conclusion: A severe degree of kinking can cause neurological symptomatology and even simulate TIA. The kinking artery should be considered as a differential diagnosis, especially in older patients and/or with risk factors. 108467 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Irreversible Bilateral Amaurosis Due to Infectious Endocarditis CYBELLE LUZA COSTA1, Cybelle Luza Costa1, Paulo Lucas Moraes Pimenta2, Fabio Queiroga1 (1) Hospital Agamenon Magalhaes; (2) Faculdade Pernambucana de Saude Introduction: Infectious endocarditis (IE) is a serious pathology caused by colonization of the cardiac endocardium, presenting itself in an insidious way, with few specific symptoms, but with catastrophic consequences if not properly treated. Due to its high morbidity and mortality, early recognition and targeted treatment can prevent irreversible sequelae. Objective: Case report of a difficult-to-diagnose infectious endocarditis in a patient assisted at Agamenon Magalhaes Hospital in Recife, Brazil. Methodology: Retrospective, qualitative, observational case report through medical chart and literature reviews. Case Report: MSJ, 79 years-old, female, arrives at the Internal Medicine service referred from a reference hospital in ophthalmology for venous antibiotic therapy after a surgical procedure in the left eye, performed for the treatment of Endogenous Endophthalmitis. She went to the hospital due to bilateral eye pain and a drop in visual acuity, evolving with only light perception in the day she sought medical care. She denied previous eye surgery or trauma. She reported being admitted to the ICU for 5 months due to sepsis and bloodstream infection, evolving after discharge with bilateral eye pain. On admission, she was clinically and hemodynamically stable, with bilateral amaurosis, with hospitalization scheduled for completion of broad-spectrum antibiotic therapy for the endophthalmitis. There was no report of fever. During hospitalization, a new systolic murmur in the mitral focus was detected in the physical examination, and a transesophageal echocardiogram (TE-ECHO) and blood cultures were performed to rule out the possibility of infectious endocarditis (IE) as the cause of endophthalmitis, since the diagnosis of this pathology would imply in extension of antibiotic therapy time. Cultures were negative, but this was not valued because of the use of intravenous Vancomycin in progress. The result of the TE-ECHO found vegetation adhered to the mitral valve, confirming the main suspicion of IE, and empirical treatment with Vancomycin and Gentamicin was performed for 6 weeks. Conclusion: IE is a disease of difficult differential diagnosis due to its symptomathological non-specificity. Therefore, it is important to know the guidelines of ESC and AHA, since the non-confirmation of the disease through one does not exclude confirmation by the other, reducing the number of underdiagnosed patients and, consequently, avoiding severe consequences. 108477 Modality: E-Poster Young Researcher - Case Report Category: CARDIO-ONCOLOGY Right Atrial Sarcoma Causing Superior Vena Cava Syndrome and Cardiac Tamponade VICTOR BAROUKI KORMANN1, Carolina Limongi de Oliveira1, Marcela Kondo Sato1, Claudinei Collatusso1, Taiana Emilio Checchia de Lima1 (1) Hospital Santa Casa de Curitiba Introduction: Based upon the data of 22 large autopsy series, the frequency of primary cardiac tumors is approximately 0.02%. Primary heart tumors are stated to occur at all ages and to have an equal sex incidence. Three quarters of the primary cardiac tumors are benign and one quarter are malignant. Myxomas and sarcomas were the most common types. Description: Patient, 34 years old, reports that in May 2021 she started with pain in the left scapular region, associated with progressive dyspnea, which became limiting for light physical activities after 3 months. Evolved with edema of the face and upper limbs, severe dyspnea, cyanosis, poor peripheral perfusion, requiring emergency pericardiocentesis. Magnetic resonance showed a tumor measuring 8.3 x 5 x 4.8 cm in the right atrium, compressing the superior vena cava and signs of cardiac tamponade. The patient underwent surgical resection of the tumor and cavity reconstruction with bovine pericardium. Biopsy confirmed the diagnosis of Angiosarcoma, with surgical margins free of neoplastic involvement. Conclusion: Cardiac tumors are rare entities, but they must be diagnosed early due to the high potential for serious complications. In this report, we present a case of right atrial sarcoma, coursing with superior vena cava syndrome and cardiac tamponade, successfully treated surgically. The patient remained asymptomatic, and no metastasis was evidenced on the tomographic study. 108544 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Spontaneous Aortic Intramural Haematoma - Case Report of the Ct Angiography Follow up Before and After Surgery DANIEL GAMA DAS NEVES1, Mario Ricardo Amar1, Rafael Vilanova Lima1, Alair Augusto Sarmet Moreira Damas dos Santos1 (1) DASA - Complexo Hospitalar de Niteroi Aortic intramural haematoma (IMH) in a type of acute aortic syndrome, in which a haematoma is formed inside the aortic wall. In this presentation we aim to report a case of acute aortic IMH diagnosed and treated in our institution, that had findings corroborating one of the etiological theories A 58-year-old female patient is admitted at the hospital after being initially evaluated in another institution of lower complexity. The patient arrived at our institution still complaining of crushing chest pain nonrelated to physical exertion, associated with dull pain in the right upper quadrant of the abdomen. Troponin and CKMB where normal but D-dimer was elevated. The medical team decides to investigate the pain with a computed tomography angiography (CTA) of the thoracic and abdominal aorta. That shows an eccentric dense thickening of the aortic wall dislocating the parietal calcifications inwards in the nonenhanced images. Contrast images showed a small irregularity in the luminal surface about 6 cm from the aortic valve plane, suggestive of a small intimal flap. The medical team then decided to admit the patient to the ICU for close surveillance and strict control the double product. After seven days of hospital care, the chest pain returned. New aortic CTA showed increase of wall thickness, formation of ulcer like projections in the ascending aortic wall covering the same location as the previously described luminal irregularity. The images also demonstrated the formation of pericardial effusion. The attending team then decides that surgery was the best course of action. The surgeons description of the procedure confirmed the location of the intimal flap described in the first CTA. Control CTA performed 10 days after the surgery showed no complications. A new CTA performed a year after the procedure demonstrated complete regression of the haematoma. This case aggregates to the body of evidence that intimal flap is a cause of not only classical aortic dissection, but also of aortic IMH. As better CT scanners becomes more available, and cardiologists, cardiovascular surgeons as well as radiologists become more aware of aortic IMHs, the understanding of this pathology will likely improve, and the diagnosis and treatment criteria may become more defined. 108541 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Case Report of Bacterial Endocarditis Caused by Staphylococcus Aureus with Involvement of Aortic, Mitral and Pulmonary Valves MARCELO VIAL FELIX DE SOUSA1, Maicon Felipe Ribeiro da Cruz1, Renata Muller Couto1, Silverio Albano Fernandes Junior1, Walter Emanoel Magalhaes Rocha1 (1) Universidade Estadual de Campinas - UNICAMP We've reported the case of a patient who has presented with symptoms of neurological alterations and, under investigation, was diagnosed with endocarditis by Staphylococcus aureus (SA) involving the mitral, aortic and pulmonary valves. A 53-year-old male sought medical attention due presenting with right arm paresis, right eyelid ptosis and diplopia. During the investigation, he developed fever, lack of appetite, weight loss and diastolic murmur in the pulmonary focus. His exams had shown positive blood culture for SA. In a transthoracic echocardiogram (TTE), vegetations were identified in the pulmonary and mitral valves. After the changes were observed, it was requested a transfer to a tertiary level hospital. In a new TTE, performed in the tertiary service, vegetations were visualized in the pulmonary valve, in the anterior leaflet of a mitral valve and in the right coronary leaflet of aortic valve. After 2 months of vancomycin, the vegetations in the aortic and mitral valves disappeared. Afterwards was performed valvuloplasty in the pulmonary valve with success. Patient maintained in outpatient follow-up without complaints so far. A review of the literature was carried out and it is not uncommon to have 2 valves involved, but the involvement of 3 valves is rare. Multivalvular involvement is related to more severe infections and has higher mortality. Despite the poor prognosis in these cases, the patient in question developed uneventfully. 109943 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Stenotic Lesion of the Left Main Coronary Artery as the Initial Manifestation of Large Vessel Vasculitis in a Sexagenarian Patient PEDRO GUIMARAES SILVA1, BRUNA MITIE IKARIMOTO1, GUILHERME RAPOSO DE MEDEIROS1, MARILIA TAILY SOLIANI1, PAULO ROGERIO SOARES1 (1) INSTITUTO DO CORACAO DO HCFMUSP Introduction: Vasculitis is a rare cause for coronary stenosis. However, it can still be responsible for life-threatening conditions. This group of diseases usually present with nonspecific symptoms and involvement of various systems. Here, we expose a case in which its initial manifestation was the development of ischemic cardiomyopathy due to a severe stenotic lesion of the left main coronary artery (LMA). Case Report: A 63-year-old woman without any previously known comorbidities began an outpatient investigation due to a 1-year history of dyspnea and angina under minimal efforts. Dilated cardiomyopathy with reduced ejection fraction (37%) was diagnosed on transthoracic echocardiography and an elective coronary angiography was requested for assessment of coronary disease A 70% focal stenosis in the distal segment of the left main coronary artery was detected, without any other significant narrowing in the other vascular beds. The patient was the admitted to the hospital for an emergent surgical revascularization. A CT angiography of the aorta and its branches was ordered. It showed a circumferential parietal thickening in the transition between the subclavian and axillary arteries to the right, determining significant segmental luminal reduction (>50%); circumferential parietal thickening of the aorta along its entire length, reaching a thickness of approximately 0.3 cm, suggestive of vasculitis. A PET-CT was ordered, which corroborated the diagnosis with the detection of diffuse and heterogeneous increase in glycolytic metabolism, of mild/moderate intensity, suggestive of an inflammatory process compatible with large-vessel vasculitis. Blood tests rendered negative for Chagas, syphilis, ANCA and antinuclear antibody serology. Pulse therapy with methylprednisolone 1 mg/kg/day was initiated and angioplasty of the LMA was performed with the use of 2 drug-eluting stents in the anterior descending and circumflex arteries, following the mini-crush and post-dilation with kissing-balloon techniques. An intra-aortic balloon was used for coronary protection during the procedure. Aspirin and Ticagrelor (60 mg in loading dose followed by maintenance 10 mg per day) were administered as antiplatelet therapy prior to the intervention. A good angiographic result and resolution of the anginal was achieved and the patient was discharged from the ward after 7 days for out-patient follow-up with a rheumatologist. 108609 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Acute Coronary Syndrome Followed by Pulmonary Thromboembolism and Identification of a Large Fixed Thrombus between Atria in a Patient with Severe COVID-19 Condition: A Case Report ALICE MIRANE MALTA CARRIJO1, Veronica Perius de Brito1, Gabriel Alvarenga Santos1, Samuel Gomes Tomaz da Silva1, Joao Lucas O'Connell1 (1) Hospital de Clinicas da Universidade Federal de Uberlandia - HC/UFU Introduction: Patent foramen ovale associated with a thrombus in transit represents a rare clinical entity difficult to manage. Its association with other thrombotic events and the hyperinflammatory state of novel coronavirus disease (COVID-19) is the subject of discussion in this study. Case description: A 69-year-old woman with grade III obesity, a history of systemic arterial hypertension, hypothyroidism and chronic venous insufficiency, was hospitalized for severe respiratory condition of COVID-19. On the 16th day of symptoms of COVID-19, the patient was diagnosed with Acute Myocardial Infarction with ST-segment elevation of the inferior wall after presenting with typical anginal pain, radiating to the left upper limb, associated with worsening dyspnea. Treatment was carried out with primary coronary angioplasty with drug-eluting stent implantation in the right coronary artery. One day after angioplasty, a routine transthoracic echocardiogram was performed, and identified preserved global systolic function of the left ventricle and the presence of a thrombus straddling the patent foramen ovale, with mobile segments in the right and left atria . Full anticoagulation with enoxaparin was initiated, acetylsalicylic acid (ASA) was maintained and clopidogrel was changed to tirofiban to schedule an embolectomy. The patient evolved with clinical stability, improvement in the respiratory condition and resolution of the atrial thrombus, documented on preoperative echocardiography , without the need for surgical embolectomy. Pulmonary artery CT angiography was performed, and confirmed a pulmonary thromboembolism (PTE). The patient remained without hemodynamic instability and ASA, clopidogrel and oral anticoagulation were maintained after hospital discharge. Conclusion: The identification of thrombus between the atria associated with the presence of patent foramen ovale is a rare event with high mortality rates, especially in the context of severe COVID-19, associated with PTE and Acute Coronary Syndrome. Management in this context is complex and there is still no consensus on the best therapy. 108633 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Typical Chest Pain in a Patient with Surgically Corrected Alcapa Syndrome: A Case Report ANA PAULA DALPICOLLI CORSO1, Alessandra Bossardi1, Bruna Valduga Dutra2, Bibiana Maggi3, Leandro Gazziero Rech4 (1) HGCS - Hospital Geral Caxias do Sul; (2) Federal University of Rio Grande do Sul UFRGS Introduction: Alcapa Syndrome (anomalous left coronary artery from the pulmonary artery) is a rare congenital disease that presents as a coronary anomaly, consisting of the origin of the left coronary artery (LCA) in the pulmonary trunk. The objective of the report is to emphasize the importance of early diagnosis of cardiac alterations to obtain better prognosis results in surgery. Case Description: A 28 years-old female sought care at the hospital due to tight retrosternal pain radiating to the left upper limb associated with dyspnea worsen on exertion in 2021. Patient reports that she had a typical chest pain episode 3 months ago, but with ECG and normal troponins. Previous history of Alcapa Syndrome, with correction of the anomalous origin of the left coronary artery in 2002. Initial laboratory assessment showed no alteration, with a troponin value of 0.005 (reference value >0.0012), and the patient was in use of furosemide. Transesophageal Echocardiography demonstrated a preserved ejection fraction with mitral valve thickening with a non-dysplastic appearance with mild regurgitation and minimal aortic valve regurgitation. At this point coronary angiography was performed, demonstrating severe stenosis in the anastomosis of the aortic tunneling. After this procedure, they underwent coronary bypass graft without complications with release to the ICU, then to the ward. After 4 days of the intervention, the patient was discharged with instruction. Conclusions: Alcapa Syndrome is a rare disease with an anomalous origin of the LCA from the pulmonary artery. There are two forms of the syndrome, infantile and adult. The adult form is characterized by the formation of a collateral system between the Right Coronary Arteries (RCA) and LCA, with a compensation usually keeping the patient asymptomatic. The patient in the case presented a complication of the tunneling previously performed. Corrected with coronary bypass graft surgery in order to restore coronary flow. 108635 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cardiac Amyloidosis: Rare Association of Val142Ile and Val50Met Pathogenic Variants GIOVANNA MARIN LESSE1, Larissa Ventura Bruscky1, Edileide Correa de Barros1, Jessika Mayhara Souza Tolentino1, Fabiano Castro Albrecht1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Cardiac amyloidosis is a underdiagnosed cause of heart failure. Hereditary transthyretin amyloidosis can occur in more than 130pathogenic variants with variable clinical presentation depending on the type of mutation. They two main phenotypes are peripheral polyneuropathy and amyloidotic heart disease. The variant Val50t is the most prevalent in the world and most important representative of the polyneur phenotype. Val142Ile is the second most prevalent and is mostly expressed with heart disease. We describe a patient who presents a rare association of these two pathogenic variants in composed heterozygosity. Case report: A 66-year-old black male patient from Juazeiro-BA, previously healthy, with a family history of neuropathy and heart disease in two brothers who died with 64 and 73 years old. She had altered sensitivity in the tips of her fingers, hands and feet, burning pain and reduced strength in her left leg and both hands for tree years. She also reported weight loss of 9 kg in two years, dizziness when assuming an orthostatic position and early satiety. Cardiological complaints were just heart palpitations during exercise and lower limb edema. In physical examination she presented with postural hypotension, rediced grip strength and pinching movement in the fingers and atrophy of the intrinsic muscles of the hands. Electrocardiogram: left anterior fascicular block and inactive zone of inferior and anterior walls. Echocardiogram: preserved left ventricle ejection fraction (global longitudinal strain of -8.7%), grade III diastolic dysfunction and enlargement of the left ventricle wall (20 mm) and interatrial septum (9 mm). Pyrophosphate scintigraphy showed pergini grade 3 uptake with a 2.22 rate. Genetic sequencing demonstrated the presence of two pathogenic variants on chromosome 18, both in heterozygosity: Val50Met and VAL142Ile. Conclusion: An association of two pathogenic variants is rare and is associated with a more severe expression of the disease and worse prognosis. In this case the apresentation was mixed: heart disease, polyneuropathy and dysautonomia, with a predominance of the last one. Heart disease symptoms were not exuberant, perhaps because of the physical limitation of the patient. However, the uptake of pyrophosphate on scintigraphy was much more intense than usual, suggesting high degree of deposit and worse prognosis. 110326 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Nuclear Medicine in the Diagnosis of Infectious Endocarditis in a Valve-in-Valve Aortic Bioprosthesis - a Case Report RAFAEL RODRIGUES COUTINHO1, Paulo Roberto Dutra da Silva1, Arnaldo Rabischoffsky1, Nilton Lavatori Correa1, Claudio Tinoco Mesquita1 (1) Hospital Pro-Cardiaco/RJ Introduction: Prosthetic valve endocarditis (PVE) has an increasing prevalence. In this case report, we sought to highlight the importance of early diagnosis in cases of previous valve-in-valve intervention. We highlight the need for integrated multidisciplinary action in an endocarditis team for the proper diagnosis. Case: Patient 86 years old, male. Hospitalized due to cough and dyspnea associated with low-grade fever and reports that he had a dental procedure two weeks ago. Previous history of heart failure functional class II, TAVI (2004 and 2021) valve-in-valve, Hypertension, dyslipidemia, smoking and alcohol consumption. He performed 2 blood cultures in the current hospitalization, positive for Streptococcus mitis. TTE and TEE without visualization of vegetations or thrombi and preserved ventricular function. CT angiography with absence of aortic vascular occlusion and shows enlarged heart and small bilateral pleural effusion. Normal lower limb venous Doppler. Scintigraphy with labelled leukocytes showing an infectious/inflammatory process in aortic valve prosthesis topography. Initiated antibiogram-guided ceftriaxone with frame resolution. Discussion: The valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) is already a well-established procedure for degenerated prosthetic valves, being also used for patients who would not tolerate open valve replacement surgery. ViV-TAVI is an alternative for high-risk patients, but there is no evidence of lower mortality of patients using this therapeutic approach compared to valve replacement surgery. Nuclear medicine emerges as a useful tool in the diagnosis of infective endocarditis, with two main evaluation modalities in this scenario, PET-CT using the 18-F-FDG agent and SPECT-CT with labelled leukocytes. Leukocytes are deposited in sites where there an active infection, being an interesting tool for suspected PVE. For the diagnosis of PVE, sensitivity and specificity of labelled leukocytes are above 90%, being then included as one of the modified DUKE criteria for infective endocarditis. Therefore, the use of SPECT-CT with labeled leukocytes has proved to be useful in the identification of PVE and should be included in the diagnostic flow of patients with suspected infective endocarditis. 108686 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING A Challenge Diagnosis in a Rare Presentation of Left Ventricular Pseudoaneurysm Obstructing Left Ventricular Inflow in the Context of Acute Myocardial Infarction JANINE DAIANA STURMER1, Raphael dos Santos Silva1, Tiago Hansel Basile Vigil1, Willer Cesar Bica1, Gabriel Soder1 (1) Instituto de Cardiologia do Rio Grande do Sul/Fundacao Universitaria de Cardiologia - ICFUC Introduction: Left ventricular (LV) pseudoaneurysm is a rare complication of myocardial infarction (MI) with high mortality rates. It consists of an intramyocardial dissecting hematoma communicating with the ventricular cavity when an injured myocardial wall rupture. The definitive diagnosis can be made with transthoracic echocardiogram (TTE) in only 26 percent of patients. Case report: A 60-year-old male with a history of smoking habit was admitted with typical chest pain lasting 20 hours. The electrocardiogram showed ST-elevation in I, aVL, V5 and V6 leads (Panel A), suggestive of lateral MI. He received dual antiplatelet therapy and was immediately transferred for coronary angiography, which displayed occluded mid-circumflex coronary artery. During the exam, he presented acute deterioration of hemodynamic state and a TTE was performed. Pericardial effusion was ruled out in subcostal-view (Panel B). At the apical 4 and 5-chamber-view the mitral valve was not visualized and in its topography a muscular band-like image that could suggest rupture of left ventricular free wall (Panel C). Finally, a long-axis-parasternal-view demonstrating a pericardial hematoma compressing the left atrium referring to a LV pseudoaneurysm (Panel D,E) which was confirmed on left ventriculography (Panel F). We theorize that as the pseudoaneurysm progressed he obstructed the LV inflow, as seen by the limited mitral valve diastolic flow at color Doppler (Panel E). The patient collapsed and died few minutes later. Conclusion: LV pseudoaneurysms can present as congestive heart failure, chest pain, arrhythmia or sudden death. Our case is a highly unusual instance of pseudoaneurysm producing severe extrinsic compression obliterating the LV inflow diagnosed with TTE in a sudden cardiac death presentation. 108710 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY A Rare Embolization of a Chemotherapy Catheter to Coronary Sinus MATHEUS HENRIQUE MENEZES1, Diogo Franca Souza Camargo1, Jose Alaor da Veiga Junior1, Deborah Christina Nercolini1, Wilton Francisco Gomes1 (1) Instituto de Neurologia e Cardiologia de Curitiba Introduction: Central venous catheters are important devices for medical care. Although they improve life-quality for patients with chronic conditions, complications are not negligible. We report a rare case of embolization of a catheter fragment into the coronary sinus. Case: A 43-years-old woman with a history of breast cancer undergoing chemotherapy through a totally implantable catheter was referred to CT scan due to a chest x-ray suggestive of a catheter fracture and embolization. CT scan images showed an embolized catheter fragment, with one extremity in the coronary sinus and the other in the right ventricle. The patient was referred for percutaneous removal of the fragment. The right femoral vein was punctured and a 10F sheath was installed. We approach the case using the "pigtail through snare" technique, using a 5F pigtail catheter placed into a 20mm loop snare before its insertion. With a 0.035 hydrophilic guidewire, we then positioned the pigtail catheter into the pulmonary artery and, with a pull-back maneuver, we successfully entangled the extremity located into the right ventricle. With coordinated movement, the snare loop was positioned right above the pigtail catheter and the guidewire inside the catheter was pushed, as an extension, allowing for the grasping of the fragment and the pigtail catheter, simultaneously. The fragment was then extracted, pulling out the assembly and sheath as a unit. Discussion: Embolization of central venous catheter fragments is uncommon, occurring in 1.1%-2.1%. The pulmonary artery and right chambers are the most frequent sites of embolization. The coronary sinus is 15-65 mm long structure and the Thebesian valve protects the ostium in almost 88% of people. This demonstrates the complexity and rarity of the case reported, with fragments in the coronary sinus and right ventricle. To our knowledge, only 6 similar cases have been reported before. The "pigtail through snare" technique seems to be a useful tool in these challenging situations. 108738 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Phaeohyphomycosis in a Heart Transplant Patient SILVERIO ALBANO FERNANDES JUNIOR1, Maicon Felipe Ribeiro da Cruz1, Marcelo Vial Felix de Sousa1, Otavio Rizzi Coelho Filho1, Wilson Nadruz Junior1 (1) Hospital de Clinicas da Universidade Estadual de Campinas - UNICAMP Introduction: Phaeohyphomycosis is a chronic fungal disease located mainly in the skin, with Fonsecaea pedrosoi being the most frequent fungus. The infection develops after a traumatic inoculation into the skin, and later, as a small papule. They may ulcerate, evolving with lymphatic or hematogenous dissemination. Infections are the main cause of death in heart transplant patients, with fungi being the third predominant etiologic agent. Case report: Male, 44 years old, vigilant, heart transplanted in 2017, using Azathioprine and Tacrolimus. He started with ulcerated lesions began, with exposure of the deep plane in the temporal region and right upper limb. About 2 months later, he developed aphasia and drowsiness. Seen on cranial tomography, frontal expansive lesion on the left, submitted to surgical resection. Diagnosed with Cerebral Chromomycosis, through the result of culture demonstrating the fungus of the genus Fonsecaea sp. Complementary treatment was performed with prolonged use of Amphotericin B during hospitalization and after discharge, replaced by Voriconazole. He was discharged from the hospital with an improvement in his neurological and skin condition. Discussion: Cerebral phaeohyphomycosis corresponds to brain infections caused by dematiaceous fungi. The predominant symptoms are produced by mass effect on the brain parenchyma. The risk of heart transplant patients presenting infection is directly related to the use of immunosuppressive drugs, such as mycophenolate and tacrolimus, which severely damage all components of immunity. Management usually combines surgical and drug treatment, the main antifungals being itraconazole, voriconazole and posaconazole. Conclusion: Phaeohyphomycosis of the central nervous system is a rare pathology in heart transplant patients. The mortality rate among patients with these infections is at least 50%, the high mortality rate highlights the need for aggressive therapy. The case described stands out for the severity of the condition, but with good resolution with combined surgical and antifungal treatment, even in the case of an immunocompromised patient. 108768 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Intimal Pulmonary Artery Sarcoma: A Differential Diagnosis of Chronic Pulmonary Thromboembolism FERNANDA MARIA FRANCO CASTRO1, FABIO MORATO DE CASTILHO1, EDUARDO BELISARIO FALCHETTO1, THIAGO PINHEIRO JUNQUEIRA1, NATHALIA SIMOES FERNANDES CAMPOS1 (1) Hospital Felicio Rocho - HFR Intimal sarcoma of the pulmonar artery is a rare and potentially lethal tumor. Its presentation is similar to pulmonary thromboembolism, what makes the diagnosis between these two diseases a clinical challenge. A 50-year-old woman was diagnosed with pulmonary embolism by Computed tomography angiography (CTA) and anticoagulated with warfarin. Despite 8 months of warfarin therapy she remained symptomatic. She complained of dyspnea and fatigue upon mild exertion. An echocardiogram demonstrated pulmonary hypertension and right ventricular dysfunction and the second CTA exam had demonstrated no change in the pulmonary artery filling defects. In view of the clinical worsening a diagnostic hypothesis of chronic pulmonary thromboembolism associated with acute thromboembolism was raised. She was referred for arteriography which showed the appearance of bilateral acute thrombi, unsuccessful mechanical thrombectomy attempt and subsequent local infusion of thrombolytic. With the findings leading towards a diagnosis of acute pulmonary embolism in a patient who was already on anticoagulant therapy, the implantation of vena cava filter was placed. Subsequently, a pulmonary artery endarterectomy was performed, which did not identify a thrombus. The material sent to anatomopathological and immunohistochemical study, has confirmed the diagnosis of intimal pulmonary artery sarcoma. The lesion was partially removed and the treatment with docetaxel and gemcitabine started with a good initial tumor response. After the surgery to remove the tumor, there was an improvement in the right ventricular function and patient's symptoms. Pulmonary artery sarcomas have no gender preference and generally occur in the fifth decade of life. Histologically, they are mostly undifferentiated or poorly differentiated tumors. The case presented here catch the attention to the need to raise the differential diagnosis in patients who do not respond to the current treatment of pulmonary thromboembolism because the treatments differ markedly and prognosis depends on the early diagnosis and prompt surgical resection of the tumor. 108837 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Unicuspid Aortic Valve: A Case Report of a Rare Condition ELISAMA PIMENTEL ZAMIAN COTIAS1, Fabricio Thebit Bortolon1, Patrick Ventorim Costa1, Herbert Felipe Heimbeck1, Berilurdes Wallacy Garcia1 (1) Hospital Universitario Cassiano Antonio Moraes (HUCAM) Unicuspid aortic valve is a rare congenital malformation associated with aortic stenosis and/or regurgitation. This condition can be categorized into two types: unicommissural and acommissural type. This case report presents a 25-year-old man, with a history of heart murmurs, dyspnea only with unusual exertion. His physical examination demonstrated an ejection systolic murmur heard loudest over the aortic valve. Transthoracic echocardiography showed concentric left ventricular hypertrophy with preserved systolic function and dome-shaped aortic valve during systole on a paraesternal long-axis view . Unicuspid aortic valve had nodule calcifications with a lateral zone of attachment to the aorta and an eccentric orifice consistent with unicommissural type on transthoracic and tridimensional transesophageal echocardiography on a short-axis view . Severe regurgitation at color doppler and severe aortic stenosis with a maximum velocity of 3.95 m/s, a mean gradient of 38 mmHg and calculated aortic valve of 0.58 cm2/m2. In conclusion, echocardiography is a solid imaging method that enables diagnosing morphological anomalies of heart valves, as well as evaluating their functioning. 108874 Modality: E-Poster Young Researcher - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Severe Gastroparesis After Atrial Fibrillation Ablation by Cryoballoon PATRICIA MATTOS VIERA DO PACO1, Olga Ferreira de Souza1, Nilson Araujo de Oliveira Junior1, Joao Pantoja1, Antonio Jose Carneiro1 (1) Hospital Copastar(HCS) Introduction: Ablation(ABL) is a safe treatment for atrial fibrillation(AF). However, injury of the anterior vagal plexus can occur when energy is applied to the posterior wall of the left atrium, resulting in gastric hypomotility, mostly oligosymptomatic and reversible. The reported case presents a patient with severe gastroparesis after cryoablation (CB). Case description: A 58 years old male patient with recent paroxysmal AF, was submitted to CB (MEDTRONIC ARCTIC FRONT II). The day after, he complained of indigestion and nausea. The symptoms were ameliorated with oral prokinetic drugs. After 10 days, he was readmitted with diffuse abdominal pain and not tolerating food and liquid ingestion. The patient was afebrile, had stable vital signs, marked abdominal distention and tenderness. CT scan showed significant gastric distention and mild diverticulitis(DI). Ciprofloxacin and metronidazole were initiated. Despite the clinical and radiologic improvement of the DI, the gastroparesis(GP) persisted. So, we ruled out any role of the DI in the GP genesis and diagnosed vagal damage due to CB. We started clarithromycin 250 mg BID to enhance gastric motility with excellent response. A new CT showed the resolution of gastric distention and a liquid diet was initiated. After a couple of days, he could eat regularly and get discharged. The figure shows the evolution of the CTs, from right to left side. Conclusions: This case helps us understand the GP related to AF ABL. Besides, he presented a second abdominal pathology, making the diagnosis difficult. The resolution was obtained from an unusual drug for this condition. Despite the protective measures there was an injury to the vagus fibers. After this case, we observed the need for further studies to seek effective protective measures. 108899 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Hypereosinophilia Associated with Spontaneous Coronary Dissection and Refractory Vasospasm: Challenges in Diagnosis and Management FELIPE REZENDE GIACOMELLI1, Marcelo Bettega1, Lara do Norte Garcia1, Julia Guidi1 (1) Hospital Israelita Albert Einstein Introduction: Acute coronary syndrome (ACS) associated with hypersensitivity represent predominantly eosinophilic and mast cell endothelial and microvascular dysfunction. This spectrum encompasses spontaneous coronary artery dissection (SCAD), non-atherosclerotic cause of ACS, and Kounis Syndrome (KS), defined by the concomitance between allergic reactions, cardiac symptoms and electrocardiographic changes after the triggering event. Case report: Male, 41 years old, with refractory asthma, chronic sinus disease, nasal polyposis, urticaria, IgG immunodeficiency and hypereosinophilic syndrome. It started in August/2021 typical anginal chest pain in the absence of ischemia on electrocardiogram, elevation of markers of myocardial necrosis (MMN) or atherosclerotic lesions on coronary angiotomography. After 2 weeks, he presented with pain, ST and MMN elevation, DACS and vasospasm in coronary angiography (CA). Angioplasty was performed, but it evolved with 2 recurrences of vasospasm refractory to intracoronary nitrate and the need for new angioplasties, totaling 6 stents. Simultaneously, there were allergic skin and respiratory manifestations, intense headache and abdominal pain. Transferred to this service after angina associated with purulent rhinosinusitis. Documented on CA nitrate-responsive vasospasm and patent stents, absence of vasculitis, myocarditis or arteritis on myocardial magnetic resonance imaging and PET-CT. Satisfactory clinical response was observed after corticosteroid therapy and optimization of antianginal agents. Conclusion: ACS and hypersensitivity are correlated with eosinophilic endothelial infiltrates, mast cell activation, and release of cytotoxic agents such as histamine and thromboxane. DACS results in disruption of the intimal layer and expansive intramural hemorrhage. In KS, cerebral and mesenteric territories are also affected and 3 coronary variables are observed:type I includes vasospasm without previous coronary artery disease; type II vasospasm with quiescent atheromatosis and type III in-stent thrombosis. Drugs, food, hives, bronchial asthma and the presence of an intracoronary stent are triggers and treatment consists of corticosteroids, antihistamines and vasodilators. Therefore, allergic angina is an underdiagnosed condition, with high morbidity, mortality and iatrogenic risk, whose treatment remains unspecific. Eosinophilstabilizing therapies and monoclonal antibodies are promising in attenuating inflammatorydependent myocardial injury. 108929 Modality: E-Poster Young Researcher - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Acute Myocardial Infarction in a Chagasic Patient: A Rare Cause of Thromboembolism LEONCIO BEM SIDRIM1, Maria das Neves Dantas da Silveira Barros2, Rodrigo Brito de Barros Correia e Silva1, Fiamma Ferreira Nogueira1, Taciana Queiroz Medeiros Gomes1 (1) Pronto Socorro Cardiologico de Pernambuco (PROCAPE); (2) Universidade de Pernambuco Introduction: Thromboembolic phenomena are frequent in patients with Chagas heart disease.1,2 Its incidence is 36% in patients with heart failure with this etiology.3 Mortality due to these complications is related, in most cases, to pulmonary and brain embolisms. 4-6 Coronary artery embolisms have been rarely described and their prevalence has not been estimated by clinical studies.2,7 Several anatomopathological and clinical studies have shown a subgroup with higher risk: presence of myocardial dysfunction, presence of intracavitary thrombi, and previous thromboembolic events. 8-10. Case description: Female, 54 years old, history of megaesophagus at 11 years of age and serological diagnosis of Chagas disease 3 years ago. No history of heart disease and no regular use of medication. Transthoracic echocardiogram (TTE) showed preserved left ventricular (LV) diastolic and systolic functions and an ejection fraction (EF) of 71%. For 30 days, she presented chest pain and tightness, in the left hemithorax and radiating to the left upper limb and mandible. Electrocardiogram (ECG) showed ST-segment elevation, measuring 2.0 mm from V2 to V4. Despite looking for the local health service, she was not submitted to emergency coronary angiography or chemical thrombolysis, with spontaneous improvement of chest pain in about 48 hours. After two weeks, the patient sought an outpatient clinic specialized in Chagas disease, reporting what had happened. A new TTE was performed, which showed: dilated LV, with hypokinesia in the anterior (middle), inferolateral (middle) and apical (septal and inferior) septum region, LV EF: 65%. The clinical history and compatible echocardiographic findings allowed the retrospective diagnosis of Acute Myocardial Infarction (AMI). Coronary angiography showed coronary arteries free from atheroma. Ventriculography showed aneurysm at the LV apex. Such findings corroborate the hypothesis of coronary thromboembolism as the etiology for AMI. Conclusion: Chagas disease is always a hypothesis to be raised in thromboembolic phenomena, given its high prevalence. Ventricular aneurysms may represent an important cardioembolic source and may be present even in patients with normal EF. The etiological definition of AMI in this case has an important practical implication for its management, given the need to use anticoagulants as opposed to antiaggregants and statins. 108961 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Reversed Cardiorespiratory Arrest in an Adult Woman with Alcapa Syndrome UANDY DIAS TERRAS1, Arthur Gabriel Soares Costa Monteiro1, Larissa Amaral de Abreu1, Larissa Rosa de Rezende1, Solange de Sousa Andrade2 (1) UNIVERSIDADE DE RIBEIRAO PRETO - UNAERP; (2) INSTITUTO DO CORACAO DA FACULDADE DE MEDICINA DA UNIVERSIDADE DE SAO PAULO Introduction: ALCAPA syndrome (known as Bland-Altman-Garland syndrome) is a rare congenital anomaly in which it occurs in the coronary arteries. We present a case report of ALCAPA syndrome in a 37-year-old female patient, who presented with syncope followed by seizures and cardiorespiratory arrest, remaining in the intensive care unit for 7 days. Case report: Brazilian citizen, female, 37 years old, residing in Santos - Sao Paulo, presented syncope followed by convulsive crisis and cardiorespiratory arrest during intense physical activity at the gym. Cardiopulmonary resuscitation maneuvers were performed for 15 minutes by the personal trainer until the Mobile and Emergency Care Service arrived, which in the initial evaluation verified a Ventricular Fibrillation (VF) rhythm and performed defibrillation with a return to sinus rhythm, palpable pulse and hemodynamically stable. She was intubated and taken to the Emergency Care Unit. Upon physical examination, it was observed that the patient was in poor general condition, Glasgow 4 and mitotic pupils. After 24 hours, the patient presented with spontaneous breathing, Glasgow 15. The Echocardiogram that showed diffuse hypokinesia of the left ventricle, more accentuated in the apical region, Ejection fraction of 52%. Coronary catheterization was requested, which showed filling of the distal third of the left coronary artery and it was not possible to catheterize the origin of this vessel. Angiotomography of the coronary arteries was then indicated, which showed the origin of the left coronary artery from the trunk of the pulmonary artery. The case was referred to the cardiac surgery team with a diagnosis of Alcapa syndrome and surgical treatment was indicated. Patient underwent cardiac surgery for reimplantation of the left coronary artery in the left coronary sinus with stable postoperative evolution and clinical improvement. One year later, the patient is asymptomatic and performs regular moderate-intensity physical activity. Conclusion: Alcapa syndrome is a rare disease among the group of anomalous coronary arteries, with a high risk of sudden death, as was presented in the case that presented a satisfactory result with the performance of cardiopulmonary resuscitation maneuvers and the correction of this anomaly was fundamental for the evolution and patient prognosis. 108985 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Rare Anatomical Anomaly of the Left Anterior Descending Artery Course VALERIA BRAGA SANTIAGO DE SA1, VALERIA BRAGA SANTIAGO DE SA1, GLAUCIENE FERREIRA DE SOUZA XAVIER2, DANIEL MEDEIROS MOREIRA1, GILVAN MAGALHAES PINTO1 (1) INSTITUTO DE CARDIOLOGIA DE SANTA CATARINA; (2) UNACON RR Introduction: Coronary artery anomalies are a diverse group of cardiac anatomical congenital disorders presenting a wide variety of clinical manifestations. Patients may be asymptomatic or have varying degrees of symptoms correlating with the anatomical presentation of the anomalous coronary path. In some cases, they may lead to sudden death. Case report: A 43-year-old Venezuelan male patient sought care presenting short-term chest pain episodes for a week. Previous medical history reported systemic hypertension treated with losartan and suffering a transient ischemic stroke 5 years ago. Electrocardiogram showed no ischemic alteration, negative myocardial necrosis markers. Coronary angiotomography presented anomalous origin of the middle and distal segments of the anterior descending artery in a way that left coronary trunk originates the circumflex artery and the proximal segment of the left anterior descending artery (LAD), which originates the 1st septal and 1st diagonal, as usual. However, the medial and distal segments of the LAD originates from the right coronary ostium with its path anterior to the pulmonary trunk until reaching the anterior interventricular groove in the middle segment, providing 2 more diagonal branches. Conclusion: This finding encourages further study and discussion regarding its potential role in the symptomatic report of this case and other similar clinical situations, helping to evaluate the need for some intervention. 108990 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Pulmonary Arteriovenous Malformation as an Etiological Factor of Stroke in Young Patients: What to Think About Beyond the Patent Foramen Ovale RAFAEL MASSUTI1, Bibiana Guimaraes Maggi1, Marcelo Sabedotti1, Rafaela Oliveira Leite2, Leandro Gazziero Rech1 (1) Hospital Geral de Caxias do Sul; (2) Fundacao Universidade de Caxias do Sul Introduction: Pulmonary arteriovenous malformations (PAVMs) are abnormal pulmonary vessels in which an artery is directly connected to a vein, forming a right-to-left shunt and resulting in clinical manifestations such as hypoxemia, predisposition to infections, and ischaemic cerebrovascular accident (CVA). Case report: Patient with a history of right hemiplegia at fifteen years old, normal hematological investigation and magnetic resonance of the encephalon at that time, and transesophageal echocardiogram demonstrating a patent foramen ovale (PFO) with a small passage of air bubbles under Valsalva maneuver, without septum aneurysm. The assistant physician discussed PFO closure, but decided for clinical management with acetylsalicylic acid, 100 mg per day. At 21-year-old, this patient seeks medical care presenting aphasia and right hemiplegia. Brain computed tomography revealed hypodense areas on the right parietal cortex region, and in left white matter, as well as encephalomalacia areas on the left brain hemisphere, suggesting vascular injury as aetiology of the stroke. Transcranial Doppler (TCD) ultrasound revealed more than 100 high-intensity transient signals (HITS), considering the Spencer Logarithmic Scale, a large shunt. Despite the lesion's anatomy, the patient improved symptoms to the absence of neurologic deficits. PFO closure was discussed once more by the assistant physician team, which opted to investigate differential embolic sources, since a PFO with such anatomical characteristics in a young patient was not considered a high risk for CVA. A pulmonary angiography revealed a massive aneurysmatic PAVM (with 3,3 cm of diameter) on the right lower lobe, nurtured by an interlobar artery branch and drained to the pulmonary vein. We proceeded with the percutaneous embolization of the PAVM through puncture of the right femoral vein and the selective catheterization of the lesion with a Progrear(r) 2.7 microcatheter. The PAVM was embolized with 8 Microplex(r) 18 coils, achieving successful occlusion of the defect. A control chest computed tomography angiography 30 days after the procedure revealed the absence of flow through the PAVM, and new TCD ultrasound demonstrated the absence of HITS. Conclusion: Even though PFO is associated with ischaemic events, ischaemic stroke in young patients must be thoroughly investigated, especially when the clinical picture is not compatible with the anatomical alterations. PAVM, although rare, must be remembered. 109221 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Transcatheter Aortic Valve Implantation in Patients with Pure Aortic Regurgitation JORDANA PIRES MENDONCA1, Flavio Rosa Vieira1, Rogerio Las Casas1, Tannas Jatene1, Vinicius Daher Vaz1 (1) Hospital do coracao Anis Rassi Introduction: Transcatheter aortic valve implantation (TAVI) for aortic stenosis has been well documented over the last years. Nevertheless, TAVI for pure aortic regurgitation (AR) it's stilll challenge due to the absence of calcification of the aortic valve and the high flow state. This features make difficult to anchor the prosthesis in the right spot, that can evolve to acute or late migration with tragic consequences. Case Description: Female 79 y/o fragile lady, at NYHA III on optimal medical therapy. At Physical examination she was tachydyspneic, with severe AR on Doppler, within 100% of the LVOT, the final velocity in the descending aorta was 2.1 m/s, mean gradient (MG) was of 21 mmHg, secondary to hyper flow, PASP of 66 mmHg. Euroscore II 8.39% and STS of 8,5%. showed aortic annulus perimeter of 76.3 mm and mean diameter of 24.3, mean sinus of Valsalva of 34 mm, left main coronary artery height of 12.8 mm and right coronary artery of 11.5 mm with zero aortic valve calcium score. After discussion with the heart team the decision to perform TAVI was made. The procedure was exceptionally performed under general anesthesia and guided by a transesophageal ECO. To secure the pacing during all the deployment a transvenous pacing was chosen. An EVOLUT Pro (Medtronic) #29 was chosen to achieve 19% of oversize. Taking into account the difficulties already anticipates, we did a full paced release. The deployment was done with pacing of 140-160 bpm in order to achieve less than 50 mm/hg of mean arterial pressure until point of no return. After careful checking with angiogram and ECO we did slow full release with 180 bpm and after we kept pacing 120 bpm for 10 minutes. The procedure duration was 69 minutes, with 60cc of contrast and without any major complications. The final MG was of only 4 mmHg and there were no paravalar leak whatsoever. The paciente was discharge from the hospital within 48 hours. At the 30-day follow-up patient has clinically improved markedly, without any further complication. Conclusion: TAVI using self-expanding prosthesis and specific deployments tips may be an alternative for patients with pure aortic regurgitation and high surgical risk or fragile profile. 108998 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Coronary-Cameral Arterial Fistula in a Child: A Case Report DOUGLAS VINICIUS DE OLIVEIRA SANTOS1, Iara dos Santos Ferreira2, Ana Caroline Mendonca Cardoso3, Ana Flavia Reis Costa4, Daniela Passos Garcia Campos5 (1) Hospital Santa Casa de Misericordia de Belo Horizonte; (2) Hospital Santa Casa de Misericordia de Belo Horizonte; (3) Hospital Santa Casa de Misericordia de Belo Horizonte; (4) Hospital Santa Casa de Misericordia de Belo Horizonte; (5) Hospital Santa Casa de Misericordia de Belo Horizonte Introduction: Arterial Coronary-cameral fistulas, congenital or acquired, are rare coronary anomalies, capable of generating serious repercussions in their carriers. We report a case of a 10-year-old child with a coronary-cameral fistula, between the right coronary artery (RCA) and right ventricle (RV). Case report: A 10-year-old female patient with asthma sought medical care denouncing recurrent fevers, associated with prostration and hyporexia, with a month of evolution. On physical examination, a heart murmur was detected, and an echocardiogram was performed suggesting Interventricular Communication (IVC). The patient was fowarded to a high complexity hospital to complete clinical, laboratory and imaging exams, in which evidenced the following: presence of lower dental arch cavities, echocardiographic findings compatible with mobile vegetations, significant regurgitation in the tricuspid valve and coronary-cameral fistula between RCA and RV. The diagnosis of infective endocarditis (IE), ACD-VD coronary-cameral arterial fistula were established, and VSD was ruled out. Antibiotic therapy was instituted (Oxacillin 200 mg/kg for 35 days, Amikacin 15 mg/kg for 22 days) and tooth extraction was performed. The patient evolved with clinical, laboratory and imaging improvement, being discharged with Amoxicillin/Clavulanate for another 7 days, along with Furosemide 40 mg/day, Carvedilol 6,25 mg/day and Beclomethasone 4 g/day. Three months later IE treatment, corrective surgery for a coronary-cameral fistula was successfully performed and all medications were discontinued. Conclusion: Coronary artery fistula with cardiac chambers are rare, being present in 0.002% of the population, representing 0.4% of all cardiac malformations. They can be congenital or acquired, the first being apparently associated with persistence of embryonic sinusoids in the myocardium. Manifestation is very variable, being capable of generating serious repercussions in approximately 19% of patients under 20 years of age, such as infarction, heart failure, cardiomyopathy, arrhythmias and IE. Heart murmur is the main semiological finding, associated with the specific symptomatology of complications. The case exemplifies the challenges of early diagnosis and treatment of coronary-camera fistulas, essential for good outcome, as well as the importance of accurate clinical and echo-Doppler evaluations, given the spectrum of manifestations and differential diagnoses, such as VSD and IE. 109000 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Atrial Fibrillation: Alternative for the Management of Anticoagulants in the Preoperative Period LEANDRO GAZZIERO RECH1, Rafaela Oliveira Leite2, Marcelo Sabedotti1, Rafael Massuti1, Bibiana Guimaraes Maggi1 (1) Hospital Geral de Caxias do Sul; (2) Fundacao Universidade de Caxias do Sul Introduction: Treating patients diagnosed with atrial fibrillation (AF) during the use of direct oral anticoagulants (DOACs) and submitted to elective surgeries is a common daily situation, but its management remains a challenge. The correct suspension period of DOACs before interventions varies according to several factors, and recent studies are committed to adopting the best way of managing these patients to minimize risks. Clinical picture: A 72-years-old female was referred to cervical arthrodesis. She had a history of surgical correction of the atrial septal defect (ASD) 20 years before, chronic AF, diabetes, arterial hypertension, and permanent pacemaker due to sinus node dysfunction. The patient was on rivaroxaban 20 mg per day, suspended 72 hours before the procedure. In the transoperative, the patient evolved to cardiac arrest in pulseless electrical activity, which returned to spontaneous circulation after two minutes of resuscitation by following the advanced cardiac life support (ACLS) protocol. In cardiogenic shock, she was referred to urgent coronary angiography, performed 20 minutes after the cardiac arrest, and the exam demonstrated coronary embolization, with a large quantity of thrombus burden, which were aspirated with a dedicated instrument. The coronary was infused with tirofiban. Hemodynamic instability was corrected with norepinephrine and crystalloids replacement, resulting in a favorable and satisfactory evolution of the instability, allowing the extubation on the same day. A transesophageal echocardiogram was performed and demonstrated spontaneous echo contrast in the left atrium and thrombus in the left atrial appendage. Despite the clinical picture, the patient did not present any degree of ventricular dysfunction. She was on enoxaparin (full dosage) during the hospitalization, and after 48 hours, we introduced Dabigatran 150 mg twice a day. The patient was discharged seven days after the occurrence, asymptomatic. Conclusion: Perioperative management of AF patients during the use of DOACs remains a challenge. Recent studies suggest individualizing treatments, which can be discontinued one to five days before the procedure, according to the surgical port, risk of bleeding, drug half-life, and renal function. Individualization remains the best strategy in addition to the possibility of non-invasive procedures for thrombosis evaluation that can corroborate clinical decisions in problematic situations. 109041 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Fistula from the Anterior Descending Artery to the Pulmonary Artery DAVID EMMANUEL BEDOYA GOYES1, Rodolfo Vaz1, Luis Antonio Machado1, Bruno Mahler Mioto1 (1) Instituto do coracao - INCOR Introduction: Coronary artery anomalies are congenital alterations that include an extensive group of malformations with a wide variety in origin, course, and distribution. Coronary artery fistula is defined as a very rare anomalous connection between a coronary artery and a cardiac chamber or a main vessel, being present in 0.002% of the population and representing 0.4% of all cardiac malformations, being asymptomatic and benign or could present with symptoms such as chest pain and cardiac dysfunction in young adults, depending on the location. Fistulas are usually diagnosed by computed tomography angiography, coronary angiography, transesophageal echocardiography, or cardiac magnetic resonance imaging. Case report A previously hypertensive, dyslipidemic 45-year-old male patient with symptoms of severe grip-related chest pain with irradiation to the mandible and left arm without other associated symptoms. Attended in the emergency room, electrocardiogram was performed without dynamic changes and markers of myocardial necrosis with slight increase; acute coronary syndrome was considered, so coronary angiography was requested, which showed the presence of an important anterior descending artery fistula (AD) for pulmonary artery trunk (AP) with QP/QS of being programmed into a second moment intervention. The patient was successfully submitted to percutaneous closure of the DA-AP fistula by embolization with interlock coil, successfully, control echocardiogram without segmental alterations, and with preserved ejection fraction. Discussion: Coronary fistulas were first described in 1865, being the first successful surgical correction in 1947; coronary artery fistulas (FAC) are congenital anomalies with an estimated incidence of 0.2 to 0.4% and are the result of persistence of primitive myocardial sinusoidal circulation and primordial epicardial vessels and may be associated with other congenital heart diseases such as arterial canal persistence, tetralogy of Fallot and interventricular communication; however, CAS can also be acquired, secondary to complications of procedures such as coronary angioplasty, myocardial revascularization surgery or after heart transplantation and myocardial biopsy. Conclusion: Coronary fistulas, despite having a low incidence among congenital heart diseases, have become increasingly frequent due to technological advances in diagnostic methods, especially in hemodynamic studies offer the possibility of treatment. 109082 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Combined Transcatheter Aortic Valve Implantation and Left Atrial Appendage Occlusion with Cerebral Protection Device GABRIEL KANHOUCHE1, Filippe Barcellos Filippini1, Pedro Felipe Gomes Nicz,1, Fabio Sandoli de Brito Jr.1, Alexandre Abizaid1 (1) Heart Institute of Sao Paulo - HCFMUSP Background: About 2-5% of patients undergoing transcatheter aortic valve implantation (TAVI) experience stroke, which substantially increases the in-hospital mortality. Atrial fibrillation (AF) prevalence in patients undergoing TAVI ranges from 16-51% and balancing the risk of cardioembolic and bleeding events represents a major challenge. We report a combined procedure strategy for treating a high bleeding risk patient with AF and severe aortic stenosis (AS). Case report: A 81-year-old woman, with past history of permanent AF, diabetes and previous pacemaker implant, evolved with heart failure class NYHA III due to severe AS. The risk-scores were CHA2DS2VASc = 6 and HAS-BLED = 3 and she was on irregular rivaroxaban use, with one prior gastrointestinal bleeding. Transesophageal echocardiogram (TEE) indicated a severe AS with aortic valve area = 0.6 cm2, mean aortic gradient = 56 mmHg, normal left ventricle function and chicken wing morphology in the left atrial appendage (LAA). After careful cardiac computed tomography evaluation, anatomy was deemed suitable for transfemoral TAVI, LAA occlusion and cerebral protection device. During Heart Team discussion, according to the intermediate risk score (STS = 6.8%), frailty, high bleeding risk and suitable anatomy, she was considered to the minimalist combined approach. First, the Sentinel cerebral protection device (Boston Scientific, CA, USA) was positioned in the brachiocephalic trunk and left carotid artery, followed by left transfemoral TAVI with Acurate Neo 2 size 25 mm (Boston Scientific, CA, USA) and right venous transfemoral LAA occlusion with Watchman FLX size 27 mm (Boston Scientific, CA, USA). Intraoperative TEE revealed absence of leak in both devices and no procedural complications. After removal of the Sentinel equipment, many embolic debris were found in the filters. She was discharged 10 days after the procedure, on aspirin use and functional class NYHA I. Clinical follow-up after 30 days was uneventful. Discussion/Conclusion: The combined procedure of TAVI and LAA occlusion with the use of a cerebral protection device followed by single antiplatelet therapy was feasible and safe. Since both TAVR and LAAO are associated with a non-negligible risk of stroke, the use of cerebral protection devices might become the standard of care for this combined approach. 109097 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Excimer Laser Coronary Atherectomy as Adjunctive Treatment of Severe Stent Underexpansion with Bulcky Calcification: A Case Report GABRIEL KANHOUCHE1, Mauricio Felippi de Sa Marchi1, Marcelo Harada Ribeiro1, Carlos Augusto Homem Magalhaes de Campos1, Henrique Barbosa Ribeiro1 (1) Heart Institute of Sao Paulo - HCFMUSP Introduction: Excimer laser catheter atherectomy (ELCA) has improved significantly in recent years, emitting high-energy ultraviolet (UV) and short wavelength with less penetration and heat emission, ultimately leading to less tissue damage and fewer complications. Case report: We described a real-life case of a 66-year-old male patient with hypertension, diabetes mellitus, dyslipidemia and former smoker. He was submitted to percutaneous coronary intervention (PCI) with bare metal stent in left descending anterior (LAD), coronary bypass in 2001 including right mammary internal artery to right coronary artery. In the past 20 years, was performed innumerous PCIs including a LAD drug eluting stent (DES) overlapping. The last LAD stent presents an acute thrombosis and was managed only with thrombolysis. A new cardiac catheterization was performed because the patients developed chest pain in the last couple months. A severe stent under-expansion in the proximal LAD was observed and ELCA was the device of choice due a overlapping underexpanded stent with bulcky calcification that make crossover the lesion with balloons or others devices impossible. A progressive load of 40/40, 60/60 and 80 mJ/mm2/80Hz and saline injection method to prepare the in-stent lesion was performed and subsequent implantation of a DES Firehawk Liberty (MicroPort, Shangai, China) 3.50 x 38 mm from the left main coronary to the LAD. Discussion: ELCA was a precise option in this case because its mechanisms of action allow reaching atherosclerosis beyond the stent without disrupting the stent architecture. The photochemical role makes dissociation of the cell's molecular bonds, the photothermal effect generated by vibration leads to the softening of collagen and protein fibers of the atheroma and the photomechanical effect generated by the explosion and implosion of the vapor bubbles leads to plaque rupture. In addition to stent under-expansion, ELCA is indicated for in-stent restenosis, calcification, balloon uncrossable lesions, and chronic total occlusion. Similar cases have been shown sporadic in the literature, but it is necessary more publication of successful results with ELCA to remove the past stigma of laser. Thereby more operators could be encouraged to use this useful device. 109141 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Alcohol Septal Ablation Before Transcatheter Valve Replacement MAURICIO FELIPPI DE SA MARCHI1, Filippe Barcellos Filippini1, Antonio Fernando Diniz Freire1, Alexandre Abizaid1, Fabio Sandoli de Brito Junior1 (1) Instituto do Coracao do Hospital das Clinicas da FMUSP (InCor) Introduction: Transcatheter Aortic Valve Replacement (TAVR) has emerged as a less invasive procedure for severe aortic stenosis. It's not rare to observe concomitant Aortic Stenosis (AS) with left ventricular outflow tract (LVOT) obstruction. This condition is mainly due to ventricular septal hypertrophy, which can potentially impact TAVR result, increasing cardiovascular mortality. We report two cases of patients with AS and high values of intraventricular gradient prior to TAVR. In both cases alcohol septal ablation (ASA) was successfully performed before TAVR. Case: 1 A 75-years-old woman with history of AS, coronary artery disease, paroxysmal nocturnal hemoglobinuria and anemia was admitted in the emergency room (ER) for sudden loss of consciousness. Her initial exams demonstrated aortic stenosis, and a 59-mmHg intraventricular gradient measured at cath lab. Considering this, ablation of the first septal artery branch was executed, with a OTW balloon and 2 mL alcohol. Residual post intervention value of the intraventricular gradient was 7 mmHg. TAVR was indicated after discussion with the Heart Team. After the procedures the patient remained assymptomatic and was referred for out-of-hospital follow-up. Case 2 An 82-years-old woman was referred for TAVR for aortic stenosis. Initial 3D echo showed significant aortic stenosis and a hypertrophic septum of 16 mm. Alcohol septal ablation was performed with an OTW balloon and 1.5 mL alcohol. Initial intraventricular gradient was 100 mmHg intervention and became 24 mmHg afterwards. A transfemoral 23 mm Sapien 3(r) was implanted. Postprocedural echo reported a 65% EF, absence of dynamic intraventricular gradient, a 23-mmHg maximum and 14 mmHg mean gradient. The patient was discharged after three days and remained in out-of-hospital follow-up. Discussion: Outflow-tract gradients of 30 mmHg or more under resting conditions are independent determinants of symptoms of progressive heart failure and death, especially threating in the context of coexistent AS. Percutaneous alcohol septal ablation is a minimally invasive procedure, which can reduce the left-ventricular outflow gradient, therefore reducing symptoms and mortality in many patients. 109151 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Treatment of Post-Endomyocardial Biopsy Fistula between Left Anterior Descending Artery and Right Ventricle with Micro-Coils MAURICIO FELIPPI DE SA MARCHI1, Gabriel Kanhouche1, Filippe Barcellos Filippini2, Luiz Junya Kajita1, Alexandre Abizaid1 (1) Instituto do Coracao do Hospital das Clinicas da FMUSP (InCor) Introduction: Endomyocardial biopsy is the gold standard for the evaluation of graft rejection following orthotropic heart transplantation. It is a relatively safe procedure, with <1% chance of serious complications. Case report: A 69-year-old patient with history of heart transplant in 2018 due to Chaga's disease underwent a 2-years control myocardial perfusion imaging scintigraphy which demonstrated minor stress-induced apical ischemia. He was asymptomatic and his last endomyocardial biopsy was 2 years ago, with no history of graft rejection. After the scintigraphy finding of ischemia a coronary angiography was performed, which displayed a fistula between the left anterior descending artery and right ventricle with subsequent coronary occlusion. This is a rare complication of endomyocardial biopsy. Fistula occlusion was planned after the scintigraphy finding. The procedure was performed with three micro-coils. First, a 5.5 x 5 mm VortX(r) (Boston Scientific) was deployed, followed by a 6.5 x 6 mm VortX(r) (Boston Scientific) and finally a 5.5 x 5 mm VortX Diamond(r) (Boston Scientific), delivered through a Renegade(r) (Boston Scientific) microcatheter. Final angiography demonstrated closure of the coronary artery fistula. After the procedure patient remained asymptomatic and was later discharged. Conclusion: We report a seldom case of fistula between left anterior descending artery and right ventricle. This patient was later successfully treated with micro-coils and was discharged for out-of-hospital follow-up. 109164 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Severe Ventricular Dysfunction and Complex Arrythmias as Manifestation of Isolated Cardiac Sarcoidosis: Case Report OLIVIA SHELLARD JUNQUEIRA FRANCO1, Rodrigo Batista Rocha1, Bruno Normande Colombo1, Rafael Augusto Mendes Domiciano1, Guilherme D'Andrea Saba Arruda1 (1) Rede D'Or - Hospital Sao Luiz Analia Franco Introduction: Cardiac sarcoidosis (CS) is considered the second most common cause of death in sarcoidosis patients globally. Isolated cardiac sarcoidosis (ICS) is defined by the absence of systemic involvement, responsible for 9% of total CS and more common in male patients. Clinical manifestations depend on the location, extent, and activity of the disease and may be evidenced as ventricular arrhythmia, high-grade block, sudden death and heart failure (HF). This is a case report of a young female with ICS initially manifested as syncope. Case description: W.C.M, 30 years, female, was admitted at the emergency room reporting palpitations and an episode of syncope during effort. Eletrocardiogram showed right bundle brunch and first-degree atrioventricular block. Due to an ejection fraction (EF) of 28% evidenced in the transthoracic echocardiogram, a cardiac magnetic resonance was indicated and showed a reduction in thickness and transmural thinning, extensive areas of fibrosis (35,9%) and myocardial edema. The endomyocardial biopsy was compatible with granulomatous miocarditis. Screnning for systemic sarcoidosis was negative. She had frequent sustained ventricular tachycardia episodes and antiarrhytmic therapy was prescribed. Treatment for HF followed current guidelines up to the maximum tolerated doses, in addition to corticosteroids and methotrexate. Hence, an implantable cardioverter-defibrillator (ICD) was implanted to prevent sudden death. After 3 months, patient remained in functional class I, there was improvement in the EF by the transthoracic echocardiogram (44% rate) and lower density of arrhythmias were observed. Conclusion: ICS has poorer prognosis when compared to CS with systemic involvement, presenting itself with lower left ventricular EF, more frequent ventricular tachycardia and ICD indication. The diagnosis may be challenging, due to endomyocardial biopsy low sensitivity. Advanced non-invasive cardiac imaging techniques may allow earlier detection of cardiac involvement. The mainstay of medical therapy for ICS is immunosuppression in addition to therapies for HF manifestations. We have reported a case of ICS with an unusual presentation in a woman with syncope. Early diagnosis, initiation of therapy and recognition of patients in risk of sudden cardiac death and demand ICD prove to be crucial. 109171 Modality: E-Poster Young Researcher - Case Report Category: CARDIO-ONCOLOGY Treatment with Inhibitor of Immunological Checkpoint and Coronary Artery Disease: An Emerging Clinical Problem NATALIA AARAO BERNARDI1, Marina Sahade Goncalves1, Fabio Sandoli de Brito Junior1, Antonio Fernando Diniz Freire1, Luana Alencar Fernandes Sampaio1 (1) Hospital Sirio Libanes Introduction: The use of immune checkpoint inhibitors (ICI), including programmed death protein inhibitors-1 (anti-PD1), brought large increases in survival, representing a paradigm shift. However, the management of immune-mediated side effects is still a challenge. Case report: A 76-year-old male patient with a history of dyslipidemia and coronary artery disease, was diagnosed with acral melanoma in the calcaneus. He started Nivolumab as the first line of systemic treatment, but before initiation, he underwent coronary angioplasty (AD - 2 stents and Mg-1 stent). After the first infusion of Nivolumab, he developed palpebral ptosis and a condition suggestive of immune-mediated myasthenic syndrome. Because symptoms worsened, it was decided to initiate immunoglobulin. During the first infusion, he presented cardiorespiratory arrest with ventricular tachycardia rhythm. Coronary angiography showed previous stents without complications and important progression of coronary artery disease compared to the examination 6 weeks before, being submitted to new angioplasty (AD - 2 stents, CD - 1stent, and balloon in Dg and VP). Cardiac magnetic resonance showed preserved biventricular function and late basal anterolateral epicardial enhancement, suggestive of a previous inflammatory process, and may represent previous inflammatory cardiomyopathy (myocarditis) or even cardiotoxicity. Data from the literature show that ICIs induce an increase in CD8+ T cells in the atherosclerotic plaque, leading to a change in the predominance of macrophages to lymphocytes in its microenvironment. Therefore, activated T cells favor the production of pro-atherogenic cytokines, contributing to the growth and destabilization of the atherosclerotic plaque. Conclusion: The profile of immune-mediated side effects can directly affect the cardiovascular system, culminating in increased morbidity and mortality in previously frail patients due to oncological diagnosis, thus demonstrating the importance of active surveillance of these patients. 109177 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Left Main Coronary Artery Aneurysm: A Therapeutic Challenge PATRICIA COSTA DE ALMEIDA1, Vitor Motta Inacio1, Bruno Azevedo da Cruz1, Felipe Jose Monassa Pitella1, Gabriel Camargo1 (1) Instituto Nacional de Cardiologia Introduction: The objective of this study is to report a rare case of a 15 mm coronary artery aneurysm (CAA) in the left main coronary artery (LMCA) in a patient with trivascular coronary artery disease (CAD), who underwent a surgical approach to CAD and conservative treatment of the coronary artery aneurysm. 68-year-old female patient with arterial hypertension, dyslipidemic and current smoker, with angina and transthoracic echocardiogram showing inferior and apical hypokinesia, with preserved left ventricular systolic function. Case report: The patient underwent stratification for CAD with myocardial perfusion scintigraphy, showing low uptake in the apical and anterior wall and a drop in ejection fraction >10% during exercise, being subsequently referred for coronary angiography with diagnosis of LMCA lesion 95% in the middle and distal third, with the presence of a 15 mm aneurysm, anterior descending artery (ADA) with 70% severe lesion in the middle third, circumflex artery (ACX) of small anatomical importance with 90% ostial lesion, diagonal branch (Dg) with severe lesion at the origin and posterior descending (PD) of the right coronary artery (RCA) with 50% in the middle third. After coronary angiography showed multivascular coronary artery disease, Coronary artery bypass graft surgery (CABG) was indicated and the treatment of the aneurysm was conservative due to technical difficulties. Discussion: Coronary aneurysms are defined as a focal dilatation of a coronary segment at least 1.5 times the size of the adjacent normal segment. The right coronary artery is generally the most affected artery (40%), with the LMCA being the least affected artery (3.5%). In contemporary studies, the incidence of true coronary aneurysms is less than 1%, with a greater predilection for males and for proximal segments of the coronary arteries. The reported clinical case contradicts the epidemiology, showing a rare case of AAC of LMCA in a female patient under investigation for CAD. Most current recommendations on coronary aneurysms are based on small case series or anecdotal reports; AAC involving LMCA, multiple or giant aneurysm. 109190 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Giant Cardiac Lipoma in the Right Atrioventricular Groove: Case Report of a Rare Lipomatose Site CATARINA MAARCHON DA SILVA2, Rodrigo A. S. Sardenberg2, Catarina Marchon da Silva1, Andrea Galvao2, Pedro Ismael Amaral Silva2 (1) Universidade Municipal de Sao Caetano do Sul; (2) Hospital Alemao Oswaldo Cruz; (3) Uniao das Faculdades dos Grandes Lagos Cardiac lipomas are rare and benign tumors. We describe a case of a giant lipoma located in the right atrioventricular groove in a 62 year-old female patient who had no related symptoms. The diagnosis was done with an echocardiogram, and confirmed through intra and postoperative histopathology. Chest angio-CT scan was compatible with giant lipoma in the RAV groove or located at the RAV groove, measuring about 9.0 x 4.5 x 5.0 cm, circling the right coronary artery (RCA), ascending aorta and compressing the right atrium, causing dilation. The patient underwent complete tumor resection and was discharged without complications. The combination of an uncommon primary tumor of the heart in a rare location (AV groove) has, according to our researches, has only been reported once in the literature, so far. Cardiac lipomas are so infrequent that no therapeutic guidelines have been established for surgical indications in such cases. They are usually benign, however, tumor embolism, growth capacity, or intracardiac obstruction can cause a dangerous situation for the patient. Consequently, complete surgical resection might be indicated even in asymptomatic patients, varying according to the patient's or the lipoma's characteristics. 109199 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Concomitant Mitraclip Implantation for Severe Mitral Regurgitation and Transcatheter Aortic Valve Implantation with Valve-in-Valve Technique in a Patient with Prior Bioprosthetic Aortic Valve Replacement and Refractory Heart Failure BRUNA SANTI DOS SANTOS1, Eduardo Schlabendorff1, Eduardo Keller Saadi1, Ana Paula Tagliari1, Marcelo Haertel Miglioranza1 (1) Hospital Mae de Deus Background: Transcatheter heart valve therapies such as mitral valve edge-to-edge repair with the MitraClip device and transcatheter aortic valve implantation (TAVI) have been demonstrated as an effective and valid therapeutic option in high-risk patients with heart failure. One-time double-valve treatment appears to be safe, feasible, and an innovative alternative. We present an exceptional case of concomitant MitraClip implantation for severe mitral regurgitation (MR) and TAVI with valve-in-valve technique in a patient with prior bioprosthetic aortic valve replacement and refractory heart failure. Case: An 80-year-old man with hypertension, diabetes, and prior bioprosthetic aortic valve replacement 6 years ago was referred to our hospital with a history of several hospitalizations for decompensated heart failure in the last 6 weeks. Besides clinical treatment optimization, he persisted with recurrent dyspnea in rest. Transthoracic echocardiography revealed severe MR with effective regurgitant orifice 80 mm2 and biological aortic valve prosthesis dysfunction with severe aortic regurgitation (AR). The left ventricle was dilated (5.8 cm/3.5 cm) and ejection fraction was 69%. This high-surgical-risk patient was accepted for concomitant transcatheter treatment with Mitraclip and TAVI valve-in-valve by the heart team, and it was well succeeded. After the procedure, the patient's symptoms improved and on discharge, he was ambulating, without dyspnea in ordinary physical activity. Conclusion: Our case illustrates a success case of concomitant MitraClip implantation for severe MR and valve-in-valve TAVI for treatment of refractory heart failure, with significant improvement of symptoms. We conclude that the combination of the two transcatheter therapies would appear to be a viable and safe approach for managing high-risk patients with concomitant severe AR and MR and refractory heart failure, and it is likely to show better results in clinical improvement if performed before severe left ventricle remodeling with severe dilation occurs due to non treated valve disease. 109620 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Sinus Venosus Atrial Septal Defect in Adult Patient - A Case Report SARAH PINI DE SOUZA1, Cintia Chaves Mattoso1, Maria Carolina Terra Cola1, Fabio Akio Nishijuka1, Thaissa Santos Monteiro1 (1) Instituto Nacional de Cardiologia Introduction: Atrial Septal Defect (ASD) can remain undiagnosed until adulthood. Sinus venosus atrial septal defects (SVASD) account for approximately 5-10% of ASDs. Associated lesions can be found, including anomalous pulmonary venous connection (APVC), persistent left superior vena cava (SVC), pulmonary valve stenosis and mitral valve prolapse. Case report: A 34 year-old male patient with a history of obesity and systemic arterial hypertension, had a known cardiac condition since he was 13 year-old, but lost follow-up and didn't know any details about the condition. He reported the dyspnea had worsened gradually in the past 20 years, especially after he was diagnosed with atrial fibrillation, when he sought again for medical follow-up. Echocardiogram (Echo) demonstrated SVASD with bidirectional shunt and pulmonary hypertension. The patient had clinical signs of systemic congestion, suggesting right ventricle dysfunction. Right heart catheterization (RHC) was performed to evaluate if the patient was still eligible for ASD closure, and it confirmed SVASD with severe pulmonary hyperflow, increased pulmonary pressures and resistance, but with satisfactory response to vasodilator. The RHC wasn't able to exclude the presence of partial APVC. The patient was then submitted to heart surgery for the ASD closure and at the procedure, anomalous drainage of two right pulmonary veins was identified, as they were connected to the SVC. For this reason, Warden repair was performed, with redirection of the APVC in the SVC through the interatrial communication into the left atrium. In the postoperative period, the patient complicated with severe pericardial effusion, requiring drainage, and was discharged 21 days after surgery. Postoperative echo showed improvement of pulmonary pressure and right ventricular function. During follow-up consultations, patient presented as NYHA I. Conclusion: Patients with ASD may remain asymptomatic until adulthood, and diagnosis delay can impact significantly in prognosis, as some complications can become irreversible. ECHO is the first line diagnostic technique and RHC is mandatory in cases of signs of pulmonary hypertension. Patients with pulmonary vascular resistance >=5 wu should be evaluated with extreme caution, considering not to proceed the ASD closure, or leastwise to maintain an interatrial fenestration. 109211 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Coronary Intervention of Kawasaki's Stenosis in an Infant MAURICIO FELIPPI DE SA MARCHI1, Cauyna Gurgel Moreira1, Gabriel Kanhouche1, Santiago Raul Arrieta1, Pedro Alves Lemos Neto1 (1) Instituto do Coracao do Hospital das Clinicas da FMUSP (InCor) Introduction: Kawasaki's disease is an acute, self-limited febrile vasculitis of unknown cause that predominantly affects children and may lead to coronary dilatation and obstruction. We report the case of a child with extreme coronary aneurysm and stenosis, treated with percutaneous coronary intervention. Case report: A 9-year-old male child was referred to our hospital with chest pain for major efforts. At age of 2, he was diagnosed with Kawasaki's and received treatment with acetylsalycilic acid (ASA) and Intravenous Immunoglobulin (IVIG). At the time, a computerized tomography angiogram large aneurysmatic dilatations in both the right coronary and the left descending arteries, measuring 11.2 mm and 10.2 mm in diameter, respectively. The patient remained asymptomatic in out-of-hospital care and received ASA and clopidogrel. He remained asymptomatic in clinical follow-up for 6 years. Due to the patient's complaints, we performed a coronary angiography which revealed a calcified giant coronary aneurysm in the LAD with a 90% focal stenosis before the aneurysm and a giant aneurysm in the RCA with a 60% focal stenosis. After the diagnostic angiography showed signs of coronary stenosis and aneurysm in the left descending artery our Heart Team opted for a new angiographic study with Intravascular Ultrassond. Due to the findings, balloon angioplasty was successfully performed, initially with semicomplacent balloon and finally with a non-complacent balloon. Angiography after the procedure demonstrated reduction of the previously documented stenosis and the patient reported relieved of the symptoms. Discussion: This case demonstrates a rare, albeit reported complication of Kawasaki's and the treatment option performed. Predisposing factors are not consensual, and an important genetic contribution is observed. Although Kawasaki's leads to coronary aneurysms in approximately 25% of untreated patients, the timely treatment IVIG has decreased this risk to 3-5% of patients. In our case, despite timely IVIG, the patient still developed two giant aneurysms. 109227 Modality: E-Poster Young Researcher - Case Report Category: ANTICOAGULATION Chronic Management of Pulmonary Embolism in Thromboangiitis Obliterans MARIANA INOCENCIO MARTINHO1, Rita Cale1, Ana Gloria Fonseca2, Melanie Ferreira2, Helder Pereira1 (1) Cadiology Department, Hospital Garcia de Orta (HGO); (2) Internal Medicine Department, Hospital Garcia de Orta (HGO) Thromboangiitis obliterans (TAO) is a rare vasculitis of young smokers affecting the small and medium sized vessels of the extremities. Although pulmonary embolism (PE) has been described, risk factors for large vessel occlusion and venous thromboembolism (VTE) recurrence are not known and there is no evidence favoring indefinite oral anticoagulation (OAC) for VTE prevention. Our first patient (pt) is an ex-smoker male diagnosed with PE and TAO at 44yo. He was under indefinite warfarin until 64yo, when OAC was switched to clopidogrel due to absence of VTE recurrence. Within 1 month, he had a massive unprovoked PE. Screening for autoimmunity (AI), antiphospholipid syndrome (APLS) and thrombophilia were negative and he was discharged under indefinite warfarin. At 7y follow-up (FUP) he had arterial ischemia but no VTE recurrence. The second pt is a male smoker diagnosed with TAO at 30yo and previous PE treated with warfarin for 6 months. AI and APLS screening were negative and he had hyperhomocysteinemia associated with MTHFR A1298C heterozigoty. At 36yo he had a submassive central PE treated with indefinite rivaroxaban. At 3y FUP despite arterial ischemia there were no VTE events. Thrombophilia and TAO have been associated and this may correlate with vessel inflammation and peripheral disease severity, but no link has been made to atypical presentation such as large vessel involvement. Hyperhomocysteinemia in MTHFR polymorphisms do not seem to increase VTE recurrence risk in the general population and do not determine prolonged OAC after a first VTE event. To our knowledge, this is the first time that this MTHFR mutation is associated with TAO. Although controversial, chronic OAC has been proposed to alleviate peripheral symptoms with some evidence suggesting that warfarin and rivaroxaban are able to reduce inflammatory markers in TAO. In both cases (the first not having any risk factor other that TAO and the second having hyperhomocysteinemia that alone should not determine secondary prevention), OAC did not prevent arterial events but seemed effective for VTE recurrence, leading us to believe that the proinflammatory state in TAO may warrant long-term OAC after a first event - as already happens with other AI diseases. Regardless, the authors acknowledge that we need more evidence to determine the most suitable approach. 109707 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Recurrent Ascending Aortic Pseudoaneurysm - Rare Complication of Rare Disease BRUNO GONCALVES GARCIA1, Igor Daumas de Souza1, Amanda Dias Bomfim1, Stephan Lachtermacher Pacheco1, Marcelo Machado Melo1 (1) National Institute of Cardiology (INC) - Rio de Janeiro, Brazil Introduction: Ascending Aortic Pseudoaneurysm (AAP) is a rare complication in cardiac surgery. It is a discontinuation of layers of vessel, with extravasated blood being contained by neighboring structures. Understanding of this rare event deserves to be discuss, in view of the potential severity of complications. Case report: Male, 46-year-old, with history of bicuspid aortic valve with aortic insufficiency, who underwent metallic aortic valve replacement in 2005. 15 years later, an increase in diameters of ascending aorta (54 mm) was observed. Submitted to implantation of a non-valved tubular graft, and reimplantation of coronary. In immediate postoperative period, patient develops infective endocarditis of aortic prosthesis, treated only with antibiotic therapy. CT angiography of the aorta 1 year after surgery reveals pseudoaneurysm of ascending aorta measuring 8.4 x 5.9 cm extending up to 9 cm to the arch, with partially thrombosed lumen, and extravasation through anastomosis of the left main coronary artery. Although asymptomatic, by the risk of progression and rupture, was submitted to surgical correction, with closure of the orifice using bovine pericardium patch. On control CT angiography 1 and 2 weeks after surgery, new contrast uptake measuring 9 mm was identified in region adjacent on origin of the coronary arteries, without progression. Re-discussion between Heart Team was made, and conservative approach chosen, with periodic short-term follow-up. Conclusion: The case shows a patient with AAP discovered accidentally, after considerable postoperative period of aortic and aortic valve manipulation. Although asymptomatic, there is a risk of generating compressive symptoms of thoracic organs. It can complicate with rupture and bleeding, in addition to being a site of infection, or thrombosis. Predisposing factors are previous manipulation of the aorta, aortotomy site, cannulation points, coronary graft anastomosis, connective tissue diseases, degenerative changes in the aorta, dissection, local infection. Regardless of size, treatment is indicated. Endovascular therapy is possible, but limited in cases of complex anatomy or active infection. Surgical approach can be performed with patch correction, or Dacron conduit. Cardiopulmonary bypass via femoral vessels is suggested for safe sternotomy. There is a risk of recurrence. Although rare, due to relevant complications, PAA should not be forgotten in the postoperative follow-up of cardiac surgeries. 109300 Modality: E-Poster Young Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Carotid Web: Report of Two Cases SUELEN DAGOSTIM GISLON1, Roberto Gabriel Salvaro1 (1) Universidade do Extremo Sul Catarinense (UNESC) The Carotid Web is a fibrous tissue projection to the carotid artery into the lumen with a pathological characteristic of intimal fibromuscular dysplasia. It is proposed as a mechanism of ischemic cerebrovascular accident (CVA) in which the hemodynamic alteration provoked can cause blood flow stagnation and clot embolisation. The main objective of this search is showed, clinically, the characteristic findings of carotid web in two different patients as well as their imaging tests. APC, female, 78 years old (patient 1), presenting complaints of headache in the occipital region radiating to the frontal region and dizziness for two months. History of Systemic Arterial Hypertension (SAH), dyslipidemia and ischemic heart disease with coronary artery bypass graft surgery in 2017. Due to the history of atherosclerosis and dizziness, an ultrasound of carotid was requested, which showed significant atheromatosis. The evaluation was complemented with carotid angiotomography (left figure), which demonstrated the presence of a linear image with a vertical orientation based on the posterior wall of the right carotid bulb, extending to the site of the internal carotid, determining stenosis in about 70%, probably related to Carotid Web, in addition to partially caicified plaques in the ostium of origin of the left vertebral column, determining stenosis in about 50%. MMF, male, 68 years old, farmer (patient 2), comes for consultation after having seizures with loss of consciousness for a few seconds. History of four CVA, SAH, venous insufficiency in the left lower limb and use of alcohol and tobacco. In investigation of stroke and embolic sources was performed Cranial Magnetic Resonance and Arterial Angio-AM of the neck (right figure), which showed Web Carotid on the right in addition to significant right vertebral lesion. Web Carotid is related to a higher risk of ischemic stroke, being important their identification to carry out the treatment and secondary prevention since the mechanism is also associated with recurrences of stroke, therefore, in some cases, dual antiplatelet aggregation or even anticoagulation is indicated. 109263 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Diagnosis of Infectious Endocarditis in Native Valve by Scintigraphy with Labeled Leukocytes JONAS PACHECO DO DESTERRO1, Rafael Rodrigues Coutinho1, Nilton Lavatori Correa1, Izabella Caterine Palazzo1, Clausio Tinoco Mesquita1 (1) Hospital Pro-Cardiaco Introduction: Infective endocarditis is an infection of the endocardium and is characterized by vegetation, an infected clot of platelets and/or fibrin, containing leukocytes and red blood cells, mainly in valve topography. The diagnosis involves clinical, laboratory and imaging criteria and the prognosis is directly related to the early initiation of treatment. Scintigraphy with MDP-99mTc-labeled leukocytes plays a key role in this pathology. Case report: We report the case of an 85-year-old female patient, hypertensive, dyslipidemic, without history of heart surgery with skin excoriations, fever, poor general condition and tachycardia. COVID19 infection was ruled out and the sepsis protocol started. The patient had leukocytosis with a left shift, elevation of CRP, lactate, massive pyuria and positive blood cultures for Staphylococcus aureus. Cranial, chest and abdomen CT scans showed no signs of infection. The transesophageal echocardiogram showed caseous degeneration in the mitral valve, and it was not possible to rule out the possibility of infective endocarditis (IE). A scintigraphy with labeled leukocytes was requested, which showed anomalous uptake in the mitral-aortic topography, confirming IE in the native valve. Conclusions: In this case report above the scintigraphic method had a crucial role confirming, with high specificity, IE of the native valve and supported the change in the therapeutic management and patient's prognosis. 109285 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Compression of the Left Main Coronary Artery by a Surgical Implanted Aortic Valve Prosthesis - a Case Report JULIANA JANGELAVICIN BARBOSA1, Fabiana Braga Sanches1, Rafael de Castro Hendges1, Silvio Marques Povoa Junior1, Pedro Silvio Farsky1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Cardiovascular disease has been the leading cause of mortality worldwide since the 1960s, including coronary syndrome and valve disease. Surgical implantation of an aortic valve prosthesis is usually a low-risk procedure, but it can be challenging in selected cases. We describe here a compression of the left main coronary artery (LMCA) by a surgical implanted Aortic Valve Prosthesis. Case report: Female patient,53 years old, dyslipidemic, HIV positive, previous coronary artery disease(CAD)-elective percutaneous coronary intervention of the left anterior descending artery in 2020,and surgical aortic valve replacement on May, 2021. On December 24 this patient presented in the Emergency room with chest pain with 2 hours duration. Initial electrocardiogram demonstrated ST-segment elevation in AvR and persistent ST-segment depression in anterolateral wall of up to 2.0 mm. Cardiac catheterization was indicated, demonstrating severe LMCA ostial lesion (90%), suggestive of extrinsic compression by the aortic bioprosthesis. Twenty four hours after the onset of the chest pain, a significant elevation of troponin was detected (12,810 ng/L - Reference value <11 ng/L). After a Heart Team Decision, emergency coronary artery bypass surgery was indicated. The patient was discharged from hospital in 4 days after a successful procedure. Conclusion: Extrinsic compression of the LMCA as a cause of acute coronary syndrome is uncommon. The literature describes cases of coronary obstruction as a complication in patients undergoing transcatheter aortic valve implantation, in cases of pulmonary hypertension and due to aneurysmal structures. However, extrinsic compression of LMCA by a surgical prosthetic valve is a very rare condition, as in this report, that may guide future therapeutic decisions in atypical cases. 109337 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Left Internal Thoracic Artery Fistula to the Bronchial Artery: A Rare Cause of Coronary Flow Theft MARCELA GOMES DE SOUZA1, Alice Mirane Malta Carrijo1, Vinicius Ferreira Aratani1, Flavia Bittar Britto Arantes1 (1) Universidade Federal de Uberlandia (UFU) Introduction: The Left Internal Thoracic Artery (LITA) fistula to the pulmonary artery and its branches is a rare clinical condition, but should be suspected in cases of persistent angina after myocardial revascularization surgery (MRS). From a pathophysiological perspective, there is a pressure difference between the vessels, resulting in coronary flow diversion and myocardial ischemia. Diagnosis requires coronary angiography and treatment may include drug therapy, surgical or endovascular intervention. Case Description: A 75-year-old man, with chronic obstructive pulmonary disease, hypertension, former smoker with a 60 pack-year smoking history. In 2014, the patient underwent MRS with LITA grafts to the anterior interventricular artery (AIA) and bypass graft to the right coronary artery, without complications. Five years later, he developed dyspnea on mild exertion, whose investigation revealed lung adenocarcinoma in the left apex, and a lobectomy was performed. After eight months, he presented with dry cough and dyspnea. The propaedeutics indicated a substernal goiter and heterogeneous thyroid, thus requiring a new surgical intervention in the mediastinum. After two months, he presented with complaints of chest pain on moderate and mild exertion associated with dyspnea. Pharmacological stress echocardiogram showed transient hypokinesia of the left ventricular anterior wall. Coronary computed tomography angiography detected an arterial fistula originating from the LITA following the lateral wall of the heart, confirmed by an angiographic study which indicated its destination for the left bronchial artery, besides blood flow diversion from the AIA. The patient underwent percutaneous embolization and trapping, with Onyx polymer and the release of six Axium micro-coils (Medtronic) into the fistular tract, via left radial access with a modified Seldinger technique. The procedure was successfully performed, and flow was immediately restored to the AIA. The patient was discharged remaining asymptomatic in the early follow-up. Conclusions: Due to the number of MRS procedures performed in the modern era and the preference for LITA as a graft, although rare, the occurrence of fistulas should be considered in cases of persistent angina after MRS. Notably, with the advancement of techniques, endovascular therapy, in addition to sparing patients from the risks of a thoracotomy, has been well documented in the treatment of symptomatic patients with a favorable anatom. 109339 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Double Jeopardy: Acute Left Anterior Descending and Right Coronary Arteries Thrombotic Subocclusions in a Young Healthy Testosterone User MARINA PETSERSEN SAADI1, Anderson Donelli da Silveira1, Guilherme Heiden Telo1, Alan Pagnoncelli1, Felipe Homem Valle1 (1) Hospital de Clinicas de Porto Alegre Background: Utilization of steroids to improve physical performance increase the risk of adverse cardiovascular events by acceleration of atherosclerosis and thrombogenesis. We report a case of acute two-vessel coronary thrombotic subocclusions in an otherwise young healthy testosterone user. Case report: 37 year-old male, bodybuilder, presented with anterolateral myocardial infarction, six hours progression. He reported steroid use since 2013, using 250 mg of intramuscular testosterone decanoate daily at this time. He was taken to primary percutaneous coronary intervention (pPCI), which depicted highly thrombotic proximal left anterior descending coronary artery (LAD) and proximal right coronary artery (RCA) subocclusions, both with TIMI III antegrade flow. Given the high thrombotic burden and the presence of normal flow, pPCI was deferred and intravenous IIb/IIIa inhibitor and unfractionated heparin were administered for the following 24 hours. Repeated angiography with coronary intravascular ultrasound assessment demonstrated an atherosclerotic plaque rupture at proximal LAD, so PCI with a drug-eluting stent strongly discouraged and aggressive secondary prevention of ischemic heart disease was initiated. Conclusion: The potential increased risk of acute coronary syndromes with exogenous testosterone administration needs to be put in perspective and the testosterone to improve physical performance should be avoided. 109365 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Ebstein Anomaly in Elderly: Case Report IZABELLA SILVA FIGUEIREDO1, PATRICIA VIEIRA DE SA1, CLEICIANE RAMOS CAPEL1, ALINE SOUZA DE OLIVEIRA1, RAFAEL LUIS FERREIRA SILVA1 (1) HOSPITAL SANTA CASA DE MISERICORDIA DE BELO HORIZONTE - HSCM BH Introduction: Ebstein's abnormality, a rare congenital heart defect caused by malformation in the posterior and septal leaflets of the tricuspid valve, has an incidence of around 1:20,000 births and a prevalence of about 0.5% among patients with congenital heart disease. It causes clear consequences on the right heart, but because the severity of anatomical alteration is variable, the clinical course of the disease is also variable, ranging from intrauterine heart failure to mild manifestations beginning in adulthood. Case Report: Female, 66 years old, history of congenital heart disease, with interatrial communication closure in 2002, atrial block - total ventricular with pacemaker placement in 2012, evolved in early 2022 with dyspnea and edema of the lower limbs of progression of 2 months. He underwent outpatient follow-up with cardiology, diagnosed with Ebstein's anomaly on the november 2021 echocardiogram, he showed important tricuspid regurgitation and valve alterations suggestive of Ebstein's anomaly, with indication of surgical correction. Admitted electively on 02/06/2022 at Hospital Santa Casa, she underwent surgery with placement of bioprosthesis in a tricuspid valve on 02/08/2022. In the immediate postoperative period, she developed cardiogenic shock and was extubated after clinical improvement on 02/15/2022. Soon after, he developed fever, leukocytosis, pulmonary congestion. Collected cultures in the catheter tip culture was isolated Staphylococcus capitis, started antibiotic vancomycin. New echocardiogram 25/02/22 that suspected endocarditis or thrombosis in the bioprosthesis. After improvement of the congestive and laboratory condition, transesophageal echocardiogram was performed, seen in the lateral leaflet of the tricuspid thrombus bioprosthesis, discarded endocarditis. Started anticoagulation with xarelto and was discharged from the hospital on 03/10/2022 for outpatient control with cardiology and cardiac surgery. Conclusion: Despite being considered the longest natural evolution of all, often exceeding until the third or fourth decade of life, acquired phenomena such as volume overload and ventricular dysfunction right affect this trajectory to the point of increasing the operative risk and morbidity in the postoperative period with the advent of arrhythmias of difficult control, in addition to the greater deterioration of ventricular function. 109370 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Nonbacterial Thrombotic Endocarditis (NBTE) in a Patient with Clear Cell Papillary Carcinoma with Implant in the Omentum, Peritoneum and Pelvis: Case Report LUCAS CAUNETO SILVEIRA1, Romulo Teixeira Vidal1, Flavio Visentin Pecci Maddalena2, Mariana Santos Gomes de Souza3, Marselha Marques Barral1 (1) Hospital e Maternidade Therezinha de Jesus - HMTJ; (2) Universidade Federal do Rio Janeiro - UFRJ/campus Macae; (3) Faculdade de Ciencias Medicas e da Saude de Juiz de Fora - SUPREMA Introduction: Nonbacterial thrombotic or marantic endocarditis (NBTE) is a rare condition of non-infectious lesions of the heart valves (mainly aortic and mitral) due to platelet deposition and hypercoagulable state, associated with neoplasms. Epidemiological data show higher prevalence in people with cancer compared to the general population (1.25% versus 0.2%, respectively), most cases are diagnosed in autopsies, with rates ranging from 0.9% to 1.6% and when compared to malignancy, it occurs more in patients with adenocarcinoma. In addition, it affects all age groups, especially in the fourth to eighth decade of life, with no predilection for sex. Overall, treatment is based on systemic anticoagulation and the surgical indications are the same as for infective endocarditis. Case Description: 49 years old female patient was hospitalized due to ischemic stroke. Transthoracic echocardiogram (TTE) showed a mobile filamentary structure adhered to the ventricular face of the aortic valve, along with a moderate aortic regurgitation. The intracranial arterial computed tomography (CT) angiography demonstrated left frontoinsular hypodensity related to ischemic vascular event without further alterations; CT scan of the abdomen and pelvis detected voluminous ascites, multiple soft tissue peritoneal formations, enhanced by contrast, sparse throughout the abdominal cavity and suggesting peritoneal implant. Furthermore, liver hypocaptant images of irregular contours was showed, mainly in segment VII, measuring 2.2 x 1.5 cm; enlarged uterus with heterogeneous density and oval formations suggesting fibroids, large solid-cystic expansive formation in the pelvis, of well-defined edges, with the solid portions enhanced by contrast measuring about 11.0 x 11.8 x 9.2 cm diagnosed ovarian neoplasm. Carotid doppler USG and thoracic aorta CT angiography was normal. Peritoneal biopsy has shown clear cell carcinoma with omentum, peritoneum and pelvis implant; patient status worsened with septic shock and respiratory failure, requiring orotracheal intubation, vasoactive drugs and intensive care unit support. After ten days, brain death was diagnosed. Conclusion: NBTE is a rare disease with high mortality, finding in advanced stages of cancer. Treatment consists in anticoagulation. 109545 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Liver Cirrhosis Secondary to Constrictive Pericarditis: Case Report FERNANDA MARIA FRANCO CASTRO1, Ludmila Stephanie Julio Machado1, Mariana Fonseca Bittencourt1, Thiago Pinheiro Junqueira1, Eduardo Belisario Falchetto1 (1) HOSPITAL FELICIO ROCHO - HFR Constrictive pericarditis is a condition associated with the development of constrictive heart failure. It results from a thickening of the pericardium, with restriction of diastolic filling of the heart and consequent decrease in cardiac output. The cause is often unknown, although it may be subsequent to any illness that causes acute pericarditis. Symptoms are related to heart failure, and may also present changes such as severe cachexia, peripheral edema, ascites, pulsatile hepatomegaly associated with congestive liver disease and pleural effusion. Physical examination findings such as pulsus paradoxus, Kussmaul's sign and pericardial knock may also be presente, but are not pathognomonic of this condition. We present the case of a 56-year-old male patient, melanoderm, hospitalized with a previous diagnosis of liver cirrhosis of undefined etiology, undergoing propaedeutic for liver transplantation. He was under irregular follow-up with a cardiologist, had a previous diagnosis of atrial fibrillation and heart failure, with a report of dyspnea that started 6 months ago, getting worse in the last 4 months associated with increase in ascites. He reported a history of tuberculosis associated with acute pericarditis for about 20 years ago. He performed a transthoracic echocardiogram whose image revealed a pericardium with increased echogenicity, mainly visceral, compatible with significant thickening, suggesting calcified constrictive pericarditis. Patient underwent surgical pericardiectomy with progressive improvement of heart and liver condition. Currently, there is no more indication for liver transplantation. Constrictive pericarditis is associated with elevated hepatic vein pressures, making patients with constrictive pericarditis prone to developing hepatic necrosis and cirrhosis. The clinical features are relatively nonspecific, making it easy to be confused with primary liver cirrhosis. Thus, a high index of suspicion for the diagnosis must be maintained. Some findings on physical examination may generate important clues (elevated jugular venous pressure, Kussmaul's sign, pericardial knock, and pericardial calcification on chest X-ray). A correct diagnosis is essential, since pericardiectomy is curative if performed early. 109417 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Case Report ANDREY ALVES DE FARIA SILVA1, Henrique Nunes Pereira Oliva2, Mariana Brandao Soares Sousa1, Isabela Oliveira Oliva3, Rita de Cassia Oliveira Araujo3 (1) Universidade Federal dos Vales do Jequitinhonha e Mucuri; (2) Yale University School of Medicine and Unimontes PPGCS; (3) UNIFIPMoc Introduction: ALCAPA Syndrome, also called Bland-Altman-Garland syndrome, is a rare congenital disease characterized by the anomalous origin of the left coronary artery from the Pulmonary Artery (AP), whose probable cause of occurrence is an embryonic alteration that affects cells of the cardiac neural crest during the early stage of embryogenesis. The present article aims to describe the rare case of anomalous origin of the left coronary artery from the pulmonary artery. Case Report: Patient D. P. A, 35 years old, male, electrical engineer, comes to a regularly scheduled review. Electrocardiogram, showed Left bundle branch block. Echocardiogram were performed, and showed akinesia and hypokinesia in lower wall. It was decided to perform a computed angiotomography of the coronary arteries, which confirmed the diagnosis of ALCAPA Syndrome. . The patient was submitted myocardial revascularization surgery, using a branch of the mammary artery to connect to the anterior descending coronary artery. In the postoperative period, the patient presented chest pain and dry cough, after 2-3 days he developed bilateral massive pulmonary thromboembolism and was hospitalized for 7 days. Pradaxa was prescribed twice a day. Conclusion: It is concluded that the ALCAPA syndrome in male adults is rare and is not well described in the literature. With the surgical correction employed, the patient evolved to improve his clinical condition. Therefore, knowledge of this condition is extremely important, since the early diagnosis and conduct provide a reduction in the patient's morbidity and mortality. REFERENCES 1. Angeline P. Revisando a Sindrome de ALCAPA dos Tipos Infantil e Adulto: as Diferencas Estao nos Detalhes. Rev Bras Cardiol Invas. 2007; 15(4). 109416 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Infarto Agudo Do Miocardio Por Doenca Aterosclerotica Coronariana Em Gestante Jovem LUAN GABRIEL PAESE1, Antonio Dejair Acosta Pazzini1, Sergio Antonio Lopez1, Romulo de Lima Moreno1, Rodney de Oliveira1 (1) Sociedade Hospitalar Angelina Caron HAC Introduction: The incidence of acute myocardial infarction (AMI) in pregnant women is low. Spontaneous coronary artery dissection is responsible for approximately 40% of AMI. Maternal mortality can reach 7%. It usually occurs in the third trimester or the immediate postpartum period. There is usually no benefit of planned cesarean delivery. The treatment is controversial and studies are still insufficient to draw definitive conclusions. Case report: Female patient, 34 years old, gestational age (GA) of 20 weeks, housewife, without comorbidities. Family history with smoker father with ischemic stroke at age 50. She was admitted to the emergency room due to chest pain, sweating and dyspnea. The electrocardiogram demonstrates sinus rhythm, subepicardial ischemia in the anteroseptal wall. Ultrasensitive troponin positive, in ascending curve. The transthoracic echocardiogram presented hypocontractility of the anterior wall, left ventricular (LV) ejection fraction of 46% and reduced global longitudinal strain (-13%). Cardiac catheterization revealed a 95% ostial lesion of the anterior descending coronary artery (AD), with thrombi throughout its extension, LV with anteroapical hypokinesia. She underwent primary angioplasty of AD with Orsiro drug-eluting stent 3.5 x 22 mm and was discharged with therapy for atherosclerotic disease (CAD). The classic presentation of AMI due to CAD is more severe in pregnant women. Unlike the high-risk population, the prevalence of atherosclerotic factors in this type of population is low. The ESC 2018 update guides the use of dual antiplatelet therapy with AAS and Clopidogrel, beta-blockers and nitrates, contraindicating the use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. It is recommended that delivery occur at least 2 weeks after the AMI, preferably vaginally. In case of a new pregnancy, it is recommended to wait a period of 12 months. Confirmed AMI in the pregnant woman, there is an indication for coronary angiography, using isosmolar contrast and protective measures. The definition of the use of balloon or stent-eluting is important. The risk of angiography is relatively small compared to its benefit for birth planning. Conclusion: The decision about the treatment to be performed is multifactorial taking into account the GA and the assessment of risks and benefits against the aforementioned drugs. The case had an good maternal evolution with hospital discharge without complications. 109422 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Hypocalcemia and Heart Failure: Case Series FRANCIELE LEIMANN1, Luiz Claudio Danzmann2, Marciane Maria Rover1, Simone Louise Savaris1 (1) Instituto de Cardiologia de Porto Alegre; (2) Universidade Luterana do Brasil Background: Heart failure (HF) is a serious health problem with high morbidity and mortality. Among the several etiologies of HF, hypocalcemia is rare, however, it is potentially fatal. Case Reports: We described three cases of female patients aged 51, 58 and 38 years, respectively, with HF secondary to hypocalcemia. Calcium deficiency occurred due to idiopathic hypoparathyroidism in one of them and hypoparathyroidism secondary to total thyroidectomy in the other two. The patients presented with signs and symptoms of HF, besides suggestive clinic of hypocalcemia, with hypoesthesia and paresthesia of extremities. In etiological research findings, serum calcium levels below 5 mg/dL were found. In two cases, there was a prolongation of the QT interval to the electrocardiogram. Furthermore, it was identified a reduction in the ejection fraction of the left ventricle (LVEF) on the echocardiogram in the three cases - at the first case with 30%, second with 19% and third with 28%. After treatment for HF associated with calcium replacement, all the patients presented an improvement of the LVEF (50%, 46%, and 62%, respectively), as well as clinical and functional status. Conclusion: The cases here presented to illustrate this situation, highlighting the risk of hypocalcemia after total thyroidectomy procedure, and also demonstrate improved function systolic and clinical symptoms with correction of hypocalcemia associated with standard therapy for heart failure. 110136 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Long Covid as a New Etiology for Heart Transplantation: A Case Series PLINIO JOSE WHITAKER WOLF1, Joao Manoel Rossi Neto1, Marco Aurelio Finger1, Carolina Casadei dos Santos1, Victor Bemfica de Mello Mattos1 (1) Instituto Dante Pazzanese de Cardiologia Background: Long COVID is a condition characterized by long-term consequences persisting or appearing after the typical convalescence period of COVID-19. It may last several months but the duration is still matter of observation. The symptoms and the clinical manifestations are clinically heterogeneous including heart failure (HF) episodes. We describe a case series of 4 patients who had long COVID and evolved to heart transplantation (Tx) indication from January/2020 to February/2022. Description: Mean age was 38 +- 9.5 years, 75% were male and 50% were Caucasian. The whole sample was admitted in NYHA IV functional class. None of the patients had more than one previous comorbidity. All had positive troponin, NT-ProBNP (20234 +- 13373) and c-reactive protein (14,7 +- 13,1). Mean time from COVID-19 infection to admission date was 150 +- 113 days and mean time from admission date to outcome was 112 +- 62,1 days. Mean Ejection Fraction (EF) was 17 +- 3,7% and 75% used Intra-aortic balloon (IAB). Two patients underwent Tx (all still alive), one died prior to Tx and one is still in the waiting list. 75% of patients had thrombotic complications awaiting Tx and all transplant patients had treated cellular rejection and Cytomegalovirus infection (table). Conclusion: HF secondary to COVID-19 due to Long COVID can progress to refractoriness to clinical treatment and Tx is the therapy of choice, showing success, despite high mortality during waiting list. 109433 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Post-COVID-19 Pericarditis: Beyond Idiopathic or Viral Etiologies NATALIA GOMES CANDIAGO1, Luiza Maria Costi Menta1, Rafael Massuti1, Tais Regina Bisol1, Bibiana Guimaraes Maggi1 (1) Hospital Geral de Caxias do Sul (HGCS) Introduction: Pericarditis is an usually mild disease with multiple possible etiological factors, including inflammatory diseases, immune responses after heart damages or viral infections, or several other chronic health conditions. Most of these cases, especially viral cases, remain undefined, as idiopathic. Case description: A 62-year-old male presented intermittent symptoms of asthenia, weight loss, thoracic pain, dyspnea, lower limb edema, vespertine fever, night sweats, and syncope on efforts. All symptoms started markedly after an infection of COVID-19, one month earlier. Patient had a familial history of leukemia, multiple sclerosis, and heart failure. The assistant physician team began a thorough outpatient investigation involving exams in search for rheumatic, collagen, neoplastic and infectious diseases. Chest tomography scans demonstrated parenchymal condensation, atelectatic striae, pleural effusion and pericardial effusion. An echocardiography demonstrated valve thickening and elicited suspicion of constrictive pericarditis. The patient evolved within months with recurrent symptoms and worst dyspnea, and so was admitted to the local hospital. A chest angiography demonstrated pulmonary thromboembolism and persistent pericardial effusion, and the patient was transferred to our hospital to assess the need for a pericardiocentesis. At our service, the diagnostic hypotheses of pericardial tuberculosis, other neoplasms and amyloidosis were raised, since the patient persisted with vespertine fever, tachycardia and night sweats during hospitalization. A new echocardiogram did not found constrictive pericarditis, with discrete improvement of findings. Patient evolved with empyema, and a cardiac magnetic resonance imaging found thickened pericardium, pericardial effusion exudate, and protein accumulation. A diagnostic videothoracoscopy was performed, with biopsy of the pericardial tissue and chest drainage. Pericardial biopsy was positive for tuberculosis, and suggestive of both chronic and acute pleuritis. Treatment with RHZE was instituted, and symptoms improved. After removal of chest drains, the patient was discharged, asymptomatic. Conclusion: Not all pericarditis are idiopathic, not even after viral infections. Tuberculosis reactivation after coronavirus infection have been frequent, and physicians must always elicit such diagnosis in light of compatible clinical histories, especially in countries of endemic tuberculosis such as Brazil. 109449 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Coronary Thrombosis and Ectasia in a Young Woman with Turner Syndrome MARINA SOUTO DA CUNHA BRENDEL BRAGA1, Anabel Lima Vieira1, Amanda Valerio Galindo1, Andrea Virginia Ferreira Chaves1, Dayse de Sena Moreira Alves1 (1) Hospital Agamenon Magalhaes Introduction: Turner syndrome (TS) is one of the most common chromosomal abnormalities, caused by the partial or total loss of the X chromosome. Among the alterations, cardiovascular disease is more prevalent, and may be congenital or acquired. Mortality rate in young women increase due to associated malformations. In the literature, coronary ectasia associated with thrombosis is not well established. Case report: F.S.G., 44 years old, female, diagnosed with Turner Syndrome and hypothyroidism, without other comorbidities, sought a cardiologic emergency due to typical chest pain, without other symptoms, 12 hours from symptom onset. She denied previous episodes. Electrocardiogram (EKG) on admission showed no acute ischemic changes. Chest radiography without abnormalities. Serum troponin with positive curve (479 -> 1746; RV: 14). Cardiac catheterization was performed with evidence of diffuse coronary ectasia and thrombus in the middle to distal third of the Circumflex Artery. Transthoracic echocardiography (TTE) showed an ejection fraction of 47% with concentric left ventricular remodeling and segmental contractile deficit (basal and medial infero-lateral hypokinesia). It was decided to start full anticoagulation with a schedule of repeat the cardiac catheterization in 07 days, which kept the same pattern. After the result, acetylsalicylic acid and rivaroxaban were started for further reassessment in 01 year. Additional evaluation of atherosclerotic disease showed no changes - lipidogram within the normal range, carotid Doppler ultrasound without plaques, bone densitometry with android/gynoid ratio indicating low cardiovascular risk. Still, chest tomography showed normal aorta. Conclusion: The association of TS with cardiovascular changes, from bicuspid aortic valve and aortic aneurysm to stroke and acute myocardial infarction, is well established in the literature. Coronary ectasia associated with thrombosis was not described as a cause of acute coronary syndrome, as occurred in the case described. This complication corroborates the need for improved cardiological knowlegde of the syndrome, aiming at proper condution and treatment. 109488 Modality: E-Poster Young Researcher - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Chronic Constrictive Tuberculous Pericarditis in a Patient with Alcoholic Liver Cirrhosis: Case Report MATHEUS LIMA LULA GUIMARAES1, Ananda Ribeiro Fretes1, Paula Maria Pinheiro Miranda1, Leticia Aparecida Braga da Silva1, Jose Sudario Cardoso Neto1 (1) Universidade Federal do Mato Grosso Introduction: Tuberculous pericarditis is an important complication of tuberculosis (TB) in developing countries. It affects up to 4% of cases of pulmonary TB and may evolve with fibrosis and calcifications causing chronic constrictive pericarditis. Case report: 58-year-old patient, male, alcoholic, smoker, under follow-up with hepatology due to alcoholic liver cirrhosis. Pathological history: untreated Atrial Fibrillation and treated pulmonary TB. He frequently complained of dyspnea on exertion, orthopnea, lower-extremity edema, ascites, occasional stabbing pain in the left hemithorax, fever, mental confusion, abdominal pain and nausea. Management of decompensated liver cirrhosis was performed, but with progressive worsening of ascites and orthopnea. Therapeutic paracentesis was performed on an outpatient basis, followed by lipothymia after the procedure, therefore, he was hospitalized for clinical compensation. On admission, he was hypotensive, tachycardic, irregular heart rhythm with hypophonetic heart sounds with splitting of the second heart sound, distended jugular veins, right-sided pleural effusion, ascites and lower-extremity edema. Echocardiogram showed preserved systolic function, enlarged hypocontractile right ventricle, significant biatrial enlargement, moderate mitral and tricuspid regurgitation, significant inferior vena cava ectasia, without respiratory variation, and hyperrefringent posterior pericardium. Chest tomography with cardiomegaly with diffuse calcifications in the pericardium, appearing to compress the ventricles and nonspecific mediastinal lymph nodes. Therefore, a diagnosis of constrictive pericarditis was made with echocardiographic criteria and clinical manifestations and of probable tuberculous etiology due to diagnosed pulmonary TB. Pericardiectomy was performed due to refractoriness to the proposed treatments (antituberculous and diuretic therapy). The patient evolved with significant improvement, with dyspnea only on great exertion, resolution of ascites and lower limb edema in subsequent consultations. Conclusion: There is a certain diagnostic difficulty in patients with liver disease due to the clinical similarity, but due to the high prevalence of tuberculous pericarditis and mortality if left untreated, we should consider such a diagnosis in patients with suggestive epidemiology. However, in a world scenario, tuberculous pericarditis is still among the often under-recognized and neglected cardiovascular diseases. 109486 Modality: E-Poster Young Researcher - Case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Sudden Death in High Performance Athlete with Bradycardia and SCN5A Gene Mutation JOAO ANTONIO DA SILVA NETO1, Joao Antonio da Silva Neto1, Patricia Alves de Oliveira1, Luciana Sacilotto1, Walace Magalhaes Barbosa2 (1) Instituto do Coracao INCOR; (2) Instituto Dante Pazzanese de Cardiologia IDPC Introduction: Sinus bradycardia (SB) at rest is considered normal in athletes and is determined by intrinsic heart rate (HR) reduction and modulations of the autonomic system. However, the possibility of progressive degeneration in association with genetic mutations that determine rhythm alterations should make the marked and persistent BS to be better investigated. Case report: Marathon runner, 28 years, SB with HR <30 bpm associated with first degree atrioventricular block (AVB) and left ventricular hypertrophy (LVH). Diagnosed with atrial flutter (AF) during a period of high-intensity training, which was treated with ablation. After 16 years of follow-up, he had an ischemic stroke (IS), treated with trombolisys, without neurologic sequelae. After developed episodes of sudden loss of consciousness, which was attributed to seizures resulting from the IS. However, the SB with pauses persisted, despite the improvement in the (LVH) pattern. HOLTER showed HR 36-48-80 bpm, BS rhythm, alternating with atrial ectopic rhythm, episodes of type I 2nd degree AVB and pauses of up to 2.7s. TILT-TEST with marked SB, 1st degree AVB and junctional escape, with accentuation of bradycardia and prolonged pauses to orthostasis, without HR response to sensitization with vasodilator, as well as with atropine. Suspecting genetic mutations that cause hereditary primary electrical diseases, a genetic test was collected. However, the patient had sudden death during sleep, before the result, which revealed a mutation of the SCN5A gene. Discussion: SB, prevalent in athletes, may be accompanied by AVB of varying degrees. In this case, in addition to marked bradycardia, the patient had AF. Despite the causal relationship between mutations in the SCN5A gene and the Brugada Syndrome phenotype, there are atypical clinical manifestations that include, in addition to the set of signs and symptoms of Brugada syndrome, AF, sinus node dysfunction, long QT syndrome, dilated cardiomyopathy, and others. Carriers of SCN5A mutations linked to Brugada syndrome or progressive cardiac conduction system degeneration are at increased risk of sudden death. Conclusion: Marked bradycardia in athletes should be investigated and the association with channelopathies leads to phenotypes with aberrant rhythms and progressive degeneration of the cardiac conduction system, which can determine fatal arrhythmias. 109497 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Post-Vaccination Myocarditis Against COVID-19: A Case Report BRUNO MIRANDA MINSKI1, RODRIGO BODANESE1, RENAN LEOTTE DE SOUZA1, NADIA MAYER2 (1) Hospital Sao Lucas - PUCRS; (2) Prefeitura Municipal de Porto Alegre Introduction: Myocarditis is inflammation of the heart muscle resulting from exposure to external antigens or internal triggers, such as autoimmune activation. Due to the coronavirus pandemic and vaccination across the world, cases of vaccine reactions have been reported. Of these, myopericarditis corresponds to approximately 0.1% of complications. As a rule, these cases are related to messenger RNA (mRNA) vaccines. Case Description: A 17-year-old man comes to the hospital with chest pain that started 2 hours ago, with oppression, without irradiation or associated symptoms. Triggered at rest, with inspiration worsening. Previously healthy, without continuous use of medication. Two days before the onset of symptoms, he received the second dose of the COVID-19 mRNA vaccine (Pfizer). The diagnosis of COVID-19 was excluded by RT-PCR. On admission he presented with BP 109/50; HR: 101; SatO2: 98%; RR: 16; BT: 36degC. Cardiac and pulmonary auscultation without significant changes. Absence of signs of congestion. Electrocardiogram (ECG) with sinus rhythm (SR), HR 74, anterior, upper lateral and inferior ST elevation and T wave inversion in the lateral wall. High Sensitivity Cardiac (HSc) Troponin I: 16,752 (RV: 34.2). Given the hypothesis of myopericarditis, he was submitted to Cardiac Magnetic Resonance Imaging (MRI), which showed: extensive late enhancement of a non-ischemic aspect and diffuse mesocardial/subepicardial edema, mainly affecting the apical, medial lateral and basal walls. Pericardial edema, more evident in the middle lateral walls of the LV. EF 44%. Findings consistent with myopericarditis. During hospitalization, he remained asymptomatic, with good clinical evolution, receiving Angiotensin Converting Enzyme Inhibitor, Beta-Blockers and Colchicine. Discharged 5 days after admission, without complaints, with a sharp drop in HSc Troponin (202). Ten days after discharge, new ECG showing RS; HR 62; anterior, superior and inferior lateral T wave inversion. After 42 days ECG of normal pattern. After 90 days of the initial event, a new MRI, which showed: reduction in the extension and thickness of the late enhancement with a non-ischemic aspect in the mesocardium/subepicardium. Virtually complete resolution of myocardial edema and pericardial changes. EF: 50%. Conclusions: The description of adverse effects of the new vaccines is essential to quicly diagnose and manage them in the most appropriate way possible, preventing unfavorable outcomes. 109503 Modality: E-Poster Young Researcher - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Single Coronary Lesion on Young Patient Diagnosed with Axenfeld-Rieger Syndrome RAMON OTT VARGAS1, Jose Carone Filho1, Schariff Moyses1, Roberto Ramos Barbosa1, Assad Miguel Sassine1 (1) Instituto de Cardiologia do Espirito Santo Introduction: Axenfeld-Rieger syndrome is an autosomal dominant genetic disease. Generally, described phenotypes consist in craniofacial and dental abnormalities, ocular anterior segment dysgenesis as well as congenital heart defects, mostly outflow tract diseases. Atrial and ventricular septal defects, valve stenosis and persistent truncus arteriosus are the most frequent cardiac presentations. The occurrence of premature coronary artery disease on these patients is not frequently documented. Case Description: Thirty year old male, diagnosed with Axenfeld-Rieger syndrome for the past twelve years, refers chest pain and oppression caused by mild efforts and daily activity, progressively worsening to limitations of any physical activities and, lately, angina at rest. Patient is eutrophic, practices physical exercise regularly, non-smoker, no diabetes or dyslipidemia and no family history for premature coronary heart disease. After being examined in clinic, laboratory exams were requested, as well as transthoracic echocardiography (TTE) and treadmill stress test. Lab results show normal cholesterol levels, glucose and triglycerides. Liver and renal functions were also normal. TTE showed no abnormalities, but the stress test was interrupted for excess tiredness and probably anginous chest pain on peak effort and recovery. Patient then presented a strong episode of angina at rest, and headed to the Emergency Room. On that occasion, a coronary angiography was requested, and showed a 90% obstruction on proximal left anterior descending artery (LAD). Percutaneous coronary intervention was performed, and a zotarolimus-eluting stent was uneventfully implanted. Patient performed well after the procedure, was discharged to home and returned to normal physical activities, maintaining follow-up in clinic. Conclusion: The occurrence of obstructive coronary lesions on young, low cardiovascular risk patients is always reason for questioning. In the described case, patient bears a rare syndrome, on which ophthalmologic and cardiac outflow tract malformations are frequently described. We hypothesize that the coronary lesion relates to this same syndrome. Further studies are necessary to evaluate this correlation. 109525 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Transcatheter Aortic Valve Implantation (TAVI) with Basilica Technique for Surgical Bioprosthesis Failure in Patient with High Risk of Coronary Occlusion FLAVIO ROSA VIEIRA1, Jordana Pires Mendonca1, Tannas Jatene1, Rogerio Lobo de Andrade Las Casas1, Vinicius Daher Vaz1 (1) Hospital do Coracao Anis Rassi Bioprosthetic disfunction is a common late complication in patients submitted to surgical aortic valve replacement. Transcatheter Aortic Valve Implantation (TAVI) valve-in-valve is an option to treat this problem according to most recent guidelines. Although rare, coronary occlusion is a potentially fatal complication after TAVI. We present a case in which we used a technique denominated BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) to prevent this adverse event. A male patient, 75 years old, hipertensive, former smoker, with ongoing dyspnea NYHA III. Physical exam revealed sistolic and diastolic murmur (3/6+) in the aortic area. Past medical history of coronary artery bypass graft in 2007, surgical bioprosthetic aortic valve replacement in 2009, percutaneous coronary intervention with stent at first diagonal branch in 2012 and 2021 (in-stent restenosis). ECG shows sinus rhythm, first degree atrioventricular block, right bundle branch block and left anterior fascicular block. Transthoracic echocardiogram identified a severe regurgitation and stenosis on the bioprosthetic aortic valve (mean gradient 41 mmHg and peak velocity 4,5 m/s). Although STS Score was 6,14% and euroSCORE II 3,45%, the patient refused his third surgery. Angio CT showed high risk for coronary occlusion (Valsalva sinus mean diameter 24 mm, left coronary height 5,5 mm and VTC 3,5 mm). Heart Team opted for TAVI with the described BASILICA technique. The intraoperatory transesofagical echocardiogram (TEE) showed mean gradient 37 mmHg and severe aortic regurgitation due to rupture in the right coronary sinus leaflet. We used a 0.014 guide wire connected to an electrocautery to perforate and tear the left leaflet. Later after pre dilatation, we finally implanted a Sapien 3 (Edwards Lifescience) # 20 bioprothesis followed by post dilation at higher pressure with a #22 non compliant balloon. The TEE showed mean gradient of 12 mmHg and no paravalvular or central leak at the final procedure. Despite the risk, the left coronary occlusion did not occur. Patient remained for 2 days at the ICU due to an increase in the PR interval, which was sustained, and was discharged 3 days after the procedure. We concluded that BASILICA technique is a feasible alternative to the patients candidates to TAVI in Valve-in-Valve with high risk for coronary occlusion. 109538 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Treatment of Severe Mitral Regurgitation Due to Previous Endocarditis in a Patient with Marfan Syndrome and Severe Symmetrical Acute Pectus Excavatum PEDRO GUIMARAES SILVA1, GUILHERME RAPOSO DE MEDEIROS1, MARILIA TAILY SOLIANI1, RONEY ORISMAR SAMPAIO1 (1) INSTITUTO DO CORACAO DO HCFMUSP Introduction: Pectus exacavatum is one of the most iconic features of Marfan syndrome. In patients who have not undergone thoracic correction during childhood, surgical treatment of valvular heart disease faces an even greater challenge. The following case report presents a patient with significant mitral regurgitation due to previous infectious endocarditis who is submitted to valve replacement along with the correction of his severe acute pectus excavatum. Case report: An 18 year-old male diagnosed with Marfan syndrome at 10 years old presented to the emergency room (ER) in February 2022 with worsening dyspnea and fatigue. He had a severe acute pectus excavatum (Haller index: 8.8), arachnodactyly, and and a positive family history of Marfan syndrome (both his father and brother). Concerning the past medical history, in 2018 he suffered from an infectious endocarditis (IE), treated only with antibiotics at the time, which caused a rupture of the tendinous cords of the mitral valve and a prolapse of both its cusps, along with the formation of a significant vegetation on the atrial aspect of the mitral anterior leaflet. He continued his outpatient treatment for 4 more years, which consisted mainly on the management of the symptoms caused by the the worsening mitral regurgitation After the admission to the ER, a transesophageal echocardiography was performed, showing a significant mitral vegetation, similar to the one described in 2018, of 21 x 6 mm along with severe mitral regurgitation; a left atrium of 230 ml/m2; and an ejection fraction was 54%. There was no involvement of the aortic valve or aortic sinus. After thorough assessment, the hypothesis of a recurrent IE was abandoned (low protein levels, no fever or other stigma of IE, and negative blood cultures) and the present condition was attributed solely to the worsening of mitral regurgitation. Chest computerized tomography presented a severe pectus excavatum with a pronounced mediastinal deviation to the left, and a total atelectasis of the left lower lung lobe Mitral valve replacement was then performed using a biological prosthesis. After closure of the left atrium, the pectus excavatum was then corrected using the Ravitch technique and Marlex mesh, without the Nuss bar (due to prolonged surgical time and detected intraoperative ventricular dysfunction). The patient evolved well during the postoperative period, with full recovery and relief of symptoms. 109570 Modality: E-Poster Young Researcher - Case Report Category: NURSING The Importance of Telemonitoring in Graft Rejection After Transplantation EVELYN GOMES OSORIO1, Kalliza Kary Rodrigues da Costa2 (1) Hospital Copa Star; (2) Hospital Copa Star Introduction: Heart transplantation (HT) is considered a therapeutic option for end-stage heart failure (HF) patients1. The occurrence of rejection is one of the post-transplant complications. Although new immunosuppressive regimens have decreased the incidence of rejection, it still represents one of the key clinical concerns. It is estimated that 25% to 80% of recipients will experience at least one episode of rejection, requiring treatment during the first year after implantation. Rejection is the cause of approximately 10% of deaths in the first year after surgery2. The nurse's role in the post-transplant follow-up and the control of adverse events is of paramount importance to detect new complications early on. The early identification of rejection will impact the prognosis and the maintenance therapy decision for the transplanted patient3. Description of the Case: Male, 39 years old, diagnosed with dilated cardiomyopathy without defined etiology about 10 years. Last echocardiogram with ejection fraction (17%), listed for HT, he searched emergency room due to progression of symptoms. He was admitted with acute cardiac insufficiency, requiring inotropic and transfer to HT reference unit where was tested for SARSCOV-2 with a positive diagnosis resulting in removal from the transplant line for 30 days. He returned in line priority subsequently, was transplanted on the 34th day. On the 10th postoperative day, the patient showed rejection grade 3R (severe rejection). The patient evolved with significant clinical improvement but presented infection by cytomegalovirus (CMV), one of the main causes of morbidity and mortality in HT in cases of recurrent or difficult to control infection4. After hospital discharge, the patient continued to be followed up by the multi-professional team, made possible through telemonitoring, the nurse's follow-up to detect early signs of aggravation, monitoring of the serum level in laboratory results to evaluate treatment accession. The treatment was based on oral corticosteroid therapy associated with immunosuppressive therapy. After 3 months of follow-up, the results of the biopsy showed an evolutionary improvement with results of 3R, 2R, and 1R. Conclusions: The outcome of the case was favorable. The advances in telemonitoring and the nurse's role have shown to be important management and follow-up tools for transplant patients at home, seeking early detection of signs of aggravation and monitoring of vascular graft disease. 109597 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Myocardial Bridge: A Clinical or Invasive Approach? SAMIA BADWAN MUSTAFA1, Samia Badwan Mustafa1, Bacila Lunks Badwan Musa3, Yasmine Badwan Mustafa2 (1) Hospital Universitario de Santa Maria; (2) Grupo Hospitalar Conceicao; (3) Clinica Medica Bacila Badwan Introduction: Myocardial bridge is a congenital anomaly, usually in the anterior descending artery (AD). It is one of the main differential diagnoses of coronary artery disease, especially when there is a low probability of atherosclerotic disease. It may manifest as angina and, rarely, acute myocardial infarction or sudden death. Case description: B.E, 39, male, military, typical anginal pain for 1 year. No comorbidities, performs physical activities. Physical examination normal. ECG: sinus rhythm, 70 bpm, left atrial and left ventricular overload. Chest X-ray normal. Echocardiogram normal. Prescribed Rosuvastatin 10 mg/day and Ramipril 5 mg. Ergometric test: ST depression. Coronary angiography: large intramyocardial bridge in AD. Clinical therapy was optimized: Nebivolol 10 mg/day, Amlodipine 10 mg, ASA 100 mg/day, suspension of Ramipril. After a year it returns with pain. Myocardial scintigraphy: no ischemic areas. Surgical evaluation requested. Conclusions: A diagnosis of a congenital condition was made based on a typical angiographic finding - systolic reduction in the diameter of the epicardial coronary artery. Although congenital, symptoms are observed later, since, due to the growth of the heart, there is an increase in the systolic tension of the myocardial wall and a reduction in coronary flow due to atherosclerotic processes. Optimized clinical treatment with beta-blockers was started, in order to reduce heart rate, increase diastolic time and reduce systolic compression of the vessel and, thus, improve anginal symptoms; antiplatelet drug to reduce the risk of cardiac events. Nitrates were avoided, as they worsen coronary artery systolic narrowing, which can worsen symptoms. Despite optimized clinical treatment, symptoms persisted, and the possibility of invasive treatment with stent implantation was discussed. However, studies have shown stent stenosis in almost half of patients undergoing angioplasty and need for reintervention in more than one third. Therefore, clinical treatment is the first line, and invasive treatment should only be considered if it is refractory to optimized clinical treatment. 109614 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Tricuspid Valve Dysplasia Mimicking Ebstein's Anomaly: A Case Report AMARILDO BORGES DA SILVA OLIVEIRA1, Allan Oliveira Macedo1, Ana Caroline Prado Pereira2, Jessica Danicki Prado Fernandes1 (1) Hospital Regional de Ceilandia - Secretaria Estadual de Saude do Distrito Federal (HRC - SES/DF)); (2) Instituto Master de Ensino Presidente Antonio Carlos - IMEPAC Itumbiara/GO Introduction: Ebstein's Anomaly (EA) is a rare congenital heart disease, characterized by abnormalities of the tricuspid valve (TV) and the right ventricle (RV), with clinical presentation varying from neonatal period to adulthood. Some echocardiographic and anatomical features are essential for diagnosis: apical displacement of the insertion of the TV septal leaflet (>=8 mm/m2), redundant elongated anterior leaflet of the TV, and RV thinning, enlargement, and dysfunction. Other comorbidities associated with TV regurgitation and right heart chambers enlargement may be misdiagnosed as EA, such as tricuspid valve dysplasia (TVD), presented in this paper, which aims to correctly identify EA and report a TVD case. Case description: MSL, female, 53 years old, dyslipidemic and diabetic, was admitted to the Emergency Unit with headache, for 4 days, associated with hypotension, sweating, general malaise and diarrhea. Later, she was transferred to a secondary hospital with signs and symptoms suggestive of B-profile decompensated heart failure. During hospitalization, an echocardiography (ECHO) was perfomed, which showed TV with thickened leaflets, apical displacement of the septal leaflet, compatible with EA. Subsequently, a new ECHO was performed with a team specialized in congenital heart diseases, which revealed a TV with redundant and dysplastic leaflets, septal leaflet with normal implantation, however, with a septum attachment with an extension of 7.5 mm/m2, not meeting the criteria for EA but for TVD. Surgical correction with valve replacement was indicated. Conclusions: EA is a complex congenital cardiac malformation with a great difference in anatomical and clinical presentations, and may be suspected in cyanotic patients, with tricuspid regurgitation, heart failure and arrhythmias, which are possible manifestations in TVD. Thus, TVD may mimic EA and its management needs to be individualized. Knowing the anatomical and hemodynamic variations, as well as the associated comorbidities, is essential for the correct recognition of cardiac involvement and management of the case, thus optimizing the patient's longevity. 109625 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS An Acute Myocardial Thrombosis Post - Covid 19 Infection and Vaccination MARCIO RAFAEL MONTICIELO1, Stefano Ramos Farias Leite1, Paula Thais Birk1, Andrieli Cristina de Oliveira1, Leonardo Gheller Zanatta1 (1) Hospital de Caridade de Ijui - HCI Acute Myocardial Infarction (AMI) is among the leading causes of death in the world. It occurs due to obstruction of coronary vessels, leading to perfusion dysfunction of cardiac areas and consequent myocardial injury, with probable failure if not treated in time. Case: Male, white, 35 year, reporting sudden-onset chest pain, approximately 30 minutes before admission, at rest, radiating to the left upper limb, malaise and sweating. He had previous systemic arterial hypertension and reported COVID-19 disease six months ago. He had been vaccinated for COVID-19 eight days before admission (OXFORD). No alcoholism or smoking. On physical examination, he had stable vital signs, cardiac and respiratory auscultation without alterations and well-perfused extremities. The electrocardiogram (ECG) showed ST elevation in leads D2, D3 and AVF, showing inferior wall AMI. Coronary angiography showed a distal thrombotic lesion in the right coronary artery (TIMI 3). At catheterization time, he was without chest pain and with preserved coronary flow (TiMI 3). We defined for pharmacological treatment with Tirofiban, Acetylsalicylic Acid, Clopidogrel and low molecular weight heparin in therapeutic dose. Some hours after, he returned with chest pain and ECG shows inferior wall AMI. A new catheterization was done and observed a significant reduction of previous thrombotic lesion but now distal occlusion of the posterior ventricular branch was verified. Once again it was decided to maintain conservative treatment due to the risk/benefit relationship. He was discharged from the hospital after complete relief of pain and decrease in the enzyme curve. He was oriented to maintaining double platelet aggregation treatment for a period of 1 year and we requested coronary CT angiography for the return. Conclusion: Studies have shown that patients with covid-19 as well as with vaccine for covid 19 are predisposed to thromboembolic events, such as peripheral and pulmonary thromboembolism, stroke, AMI and acute lower limb ischemia. The fact that these patients had no risk factors for CAD and did not have coronary atherosclerotic plaques raises the possibility that the thrombotic event is associated with the hypercoagulable state of the covid-19/vaccine infection. More aggressive pharmacological therapy, such as fibrinolytics, glycoprotein IIb/IIIa inhibitor and prolonged use of anticoagulants, in these cases, in view of the high thrombotic load, replacing angioplasty, should be considered. 109659 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Coronary Artery Compression by Post-Traumatic Left Ventricular Pseudoaneurysm: A Case Report BRENO DE ALENCAR ANTAO1, Raysa Ramos Santos Negromonte1, Anabel Lima Vieira1, Maria de Fatima Nunes de Oliveira1, Maria Dolores da Trindade Henriques Assuncao1 (1) Hospital Agamenon Magalhaes Introduction: A left ventricular pseudoaneurysm (LVP) it is the result of cardiac rupture contained by adherent pericardium or scar tissue. Unlike true aneurysm, it does not contain endocardium or myocardium. Most of the LVP occurs after transmural myocardial infarction but also occurs after cardiac surgery, trauma, or infection. We describe a case of LVP after blunt chest trauma incidentally occurring with valvular heart failure. Case report: J.S.S., a 60-year-old male was admitted with dyspnea on mild exertion, orthopnea, paroxysmal nocturnal dyspnea, and lower limb edema. He had a mitral bioprosthesis (MB) since 2013 due to a blunt chest trauma caused by motor vehicle accident that led to acute mitral regurgitation (MR) as result of ruptured chordae tendineae. Initial echocardiogram (ECHO) revealed preserved systolic function with moderate tricuspid regurgitation, moderate pulmonary arterial hypertension and dysfunctional mitral bioprosthesis. Pre-surgical catheterization revealed anterior descending artery, 2nd diagonal branch and circumflex artery with significant luminal reduction during systole, without signs of coronary atheromatosis. Coronary angiotomography was requested evidenced a pseudoaneurysm in the basal segment of the anterior wall of the left ventricle with slight extrinsic circumflex artery compression. Patient underwent MB replacement and the LVP, which was below the aortic valve plane, measuring 1.3 cm in diameter, was repaired with implantation of a bovine pericardium patch. There was a postoperative bleeding successfully managed. New ECHO revealed normal implantation and fixation of BM, normal LV systolic function with moderate right chamber insufficiency and without evidence of a pseudoaneurysm. Patient had clinical improvement after procedures and remains in outpatient follow-up. Discussion: According to the literature, up to 80% of blunt cardiac injuries are caused by motor vehicle collisions (MVC) widely ranging from LVP to the ventricular free wall rupture. Untreated pseudoaneurysms have rupture risk (30% to 45%) and high mortality rate (almost 50%) with clinical treatment. Patients with severe MR have a higher risk which requires mitral valve replacement, as in the case described. Correct diagnosis and appropriate surgical management lead to reduced mortality and better prognosis. 109722 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Stanford a Chronic Aortic Dissection in a High-Risk Surgical Patient and Decision for Clinical Treatment: Case Report KELSON KEMUEL CONFESSOR DE SOUSA1, Kelton Dantas Pereira1, Vinicius Pereira Dantas1, Ana Olivia Dantas2, Fabio Mastrocola1 (1) Onofre Lopes University Hospital; (2) Federal University of Rio Grande do Norte Introduction: Aortic dissection is marked by the delamination of the middle layer of this vessel due to the inflow of blood. According to the Stanford classification, the ascending aorta (type A) or the descending aorta (type B) may be affected. Some studies show that the mortality of patients with type A acute dissection treated surgically is 26%, while that of those not undergoing surgery, due to advanced age or comorbidities, was about 58%. There are no data on mortality in chronic dissections. Case report: A 78-year-old female patient, with obesity, chronic hypertension and frailty syndrome, started with a sudden loss of muscle strength and dysarthria, being diagnosed with ischemic stroke. During investigation of the present clinical scenario, the Transthoracic Echocardiogram showed a Stanford type A dissecting aortic aneurysm measuring 68 mm. An angiotomography of the thoracoabdominal aorta showed a fusiform aneurysm of the ascending aorta, measuring 7.3 cm with signs of chronic aortic dissection, extending from the aortic valve annulus to the infra-renal abdominal segment. The patient was then also submitted to coronary evaluation, which showed multivessel coronary artery disease. In view of the chronic dissection of the ascending aorta, which treatment currently established is to replace the affected aortic segment, and considering the multiple comorbidities peculiar to this patient at high surgical risk, the clinical and surgical team considered that the surgery would bring more risks than the potential benefit. Thus, the patient was discharged with adequate blood pressure and heart rate control. Conclusion: Acute type A aortic dissection is the cardiovascular lesion with the highest mortality if not treated immediately, reaching a rate of 80% in about 14 days, with surgical treatment being one of the only possible approaches for both acute and chronic cases. There are complex and challenging cases such as the one described above in which the risk versus benefit must be weighed, as the patient has already passed the high mortality phase. Furthermore, the current medical literature is not clear about the mortality estimate in the scenario of chronic aortic dissection, which led us to choose a conservative approach in a patient at high surgical risk. This patient has been under follow-up for more than 6 months, an outcome that could be different if the surgical procedure had been chosen at the initial moment. 109749 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Loeffler's Endomyocardial Disease: A Rare Cause of Heart Failure GABRIELA ASSIS RANGEL DE ABREU1, Lucas Feldman Paz de Lima1, Angelo Antunes Salgado1, Marcos Paulo Lacerda Bernardo1, Joaquim Henrique de Souza Aguiar Coutinho1 (1) Hospital Universitario Pedro Ernesto Introduction: Loeffler's endomyocardial disease is a rare disease caused by eosinophil infiltration into the endomyocardial. Heart failure characterizes the clinical picture, secondary to the restrictive behavior of the ventricle, triggered by fibrosis and obliteration of the ventricular cavities. The treatment targets the etiology of eosinophilia, which often remains unknown. Case: Male, 62, started outpatient follow-up in hematology for eosinophilia and splenomegaly. The laboratory showed leukocytosis of 36,090/mm3 with eosinophils 21,645/mm3 (60%). An investigation was carried out but without etiological elucidation. A transthoracic echocardiogram (TTE) showed biatrial enlargement, preserved biventricular function, type 2 diastolic dysfunction (DD), and increased thickness of the apical segments of both ventricles, suggestive of infiltrative disease. After one month, he presented ascites and dyspnea requiring hospitalization. A new TTE revealed type 3 DD, right ventricular systolic dysfunction with severe tricuspid regurgitation due to coaptation failure, and worsening of ventricular infiltration, obliterating more than 50% of the cavities. During hospitalization, the patient evolved with low cardiac output refractory to pharmacological therapy without improving eosinophilia despite corticosteroid. He then underwent endocardiectomy and biological tricuspid valve replacement; nevertheless, he came to death one day after surgery. Conclusion: Loeffler's endomyocardial disease is a subcategory of the hypereosinophilic syndrome, with 2D TTE being the primary imaging method for diagnosis and follow-up. In this case, the lack of etiology, corticosteroid refractoriness, and fast progression of biventricular apical obliteration made the case difficult to handle and a worse prognosis. 109814 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Transcatheter Edge-to-Edge Mitral Valve Repair to Improve Heart Transplant Candidacy in Worsening Pulmonary Hypertension: A Case Report PEDRO CASTILHOS DE FREITAS CRIVELARO1, Nadine Oliveira Clausell1, Felipe Homem Valle1, Livia Adams Goldraich1, Leonardo Hennig Bridi1 (1) Hospital de Clinicas de Porto Alegre HCPA Background: Transcatheter edge-to-edge mitral valve repair (TEER) has been utilized as a potential therapeutic strategy in selected patients with advanced heart failure. According to a multicenter retrospective registry, TEER may promote clinical improvement and pulmonary hypertension relief as bridge to transplantation or to candidancy. Report: A 57-year-old male with ischemic cardiomyopathy and recently worsened severe functional mitral regurgitation (MR) was admitted with advanced heart failure and listed for transplant. Clinical status worsening, with intravenous inotropic support increases and temporary mechanical circulatory support followed. Hemodynamic assessments showed heart failure progression with fixed severe pulmonary hypertension and remarkably poor cardiac performance. Transplant was then deemed to be of high risk, and the patient was inactivated on the waiting list. TEER was considered as a "bridge to candidancy" and it was carried with the implantation of 2 XTw MitraClip(r) (Abbott Vascular) devices. Remarkable reduction on both MR severity and left atrial V-wave pressure were achieved. Functional and hemodynamic status dramatically improved and the patient was reactivated on the heart transplant waiting list at 30-day follow-up. Conclusion: TEER may be a feasible option in selected heart transplant candidates to improve severe pulmonary hypertension. 109858 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Valve-in-Valve Mitral in Patient with Thrombus in Left Atrial Appendage: The Importance of Brain Protection with SentinelTM Device and Appendage Occlusion with WatchmanTM Prosthesis in the Same Procedure JOAO CARLOS MATOS PINTO JUNIOR1, Luiz Felipe M F Alves1, Joao Luiz Frighetto1, Lisley Riano da Silva Pestana1, Estevao Carvalho de Campos Martins1 (1) Hospital de Forca Aerea do Galeao Introduction: Rheumatic valve disease still is a prevalent condition in our country. Even when young, affected patients evolve the need of mitral valve replacement. Subsequent valve dysfunctions, predominantly in mitral valves, generate structural and pathological consequences, primary or secundary. Thromboembolic phenomenons and the increased operative risk in the classical surgical approaches confers a higher risk of morbidity and mortality to those patients. Modern strategies and devices for percutaneous treatment emerge as an option for a better approach. Case description: 78 years old, female, with hypertension and permanent atrial fibrillation. Evolves with worsening of functional class, signs of congestion, requiring hospital admission and intravenous diuretic therapy. This patient have a history of biological mitral valve replacement due to rheumatic valve disease. The first one was in 1968 and the second one was in 2000. She had a subarachnoid hemorrhage event in 2020. Evolves with worsening functional class, with signs of system congestion, requiring the use of intravenous diuretic therapy. After clinical stabilization, a transesophageal echocardiogram was performed, revealing an LA enlargement and a severe degeneration of the biological mitral prothesis with calcified and poorly mobile bases including a eversion of one of these leaflets into the left atrium, causing a severe mitral regurgitation, with a transprosthetic gradient. maximum 21 mmHg and average 9 mmHg, Peak Velocity 2.3 m/s, PHT 179 ms, AEO 1 cm2, and presence of thrombus in the left atrium Due high surgical risk, percutaneous treatment was chosen with a VIV - "Valve in Valve" strategy preceded by central nervous system protection with the SentinelTM device on the brachiouscefalic trunk and the left internal carotid beside Left Atrial Appendage with the watchmanTM flex. Conclusion: The treatment of valve degeneration in elderly patients with previous biological valve replacement is still challenging, with the advent of percutaneous treatment (Valve-in-valve), which has brought new perspectives to those patients. The use of devices such as sentinelTM and watchmanTM help to prevent one of the main complications, which is embolism to the central nervous system. References: Little SH, Bapat V, Blanke P, Guerrero M, Rajagopal V, Siegel R. Imaging Guidance for Transcatheter Mitral Valve Intervention on Prosthetic Valves, Rings, and Annular Calcification. JACC Cardiovasc Imaging. 20. 109870 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Acute Pericarditis and Pericardial Effusion After COVID-19 Infection RAQUEL SILVA BRITO DA LUZ1, Adnaldo da Silveira Maia1, Arturo Adrian Jara1, Janayna Rabelato1, Antonio Flavio Sanchez1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: COVID-19 infection has a wide spectrum of clinical presentations, including cardiovascular, including myocarditis and pericarditis. The prevalence and events associated with this condition still remain under analysis, as well as the repercussion of such complications after the viral infection. Case Description: 74-year-old female patient, former smoker, bilateral carotid stenosis without hemodynamic repercussions, rheumatoid arthritis and diagnosis of viral pneumonia due to COVID-19 in January 2022. She was admitted, in March 2022, to a referral center in cardiovascular diseases, with a clinical picture of chest pain that worsened during inspiration with 2 months of evolution. Laboratory measurements of troponin and D-dimer within normal limits. Admission electrocardiogram suggestive of pericarditis. Transthoracic echocardiogram (TTECT) revealed preserved biventricular function and pericardial effusion with a greater depth of 11.0 mm. Despite the optimized clinical treatment for the pericarditis, the patient evolved with clinical worsening and rapid evolution of the pericardial effusion initially evident, with a 30.0 mm blade and signs of hemodynamic repercussion, requiring urgent drainage. On the 1st postoperative day in the intensive care unit, the patient evolved with severe acute biventricular dysfunction and need for vasoactive drugs, without response to the established clinical measures, progressing to death. Conclusion: The prevalence of underlying pericarditis and pericardial effusion in patients with COVID-19, as well as its clinical significance remains the subject of clinical research. Thus, knowing risk factors and the pathophysiology of cardiovascular complications related to COVID-19 are sine qua non conditions for understanding the clinical presentation, prognosis and therapeutic management. 109879 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY A Unique Case of Stent Kinking SEPIDEH DARBANDI1, Samuel Congello1, Ali Mardan1 (1) MercyOne North Iowa Medical Center Patient is a 62 year old male with past medical history of tobacco abuse who had presented with abrupt onset of pain and paralysis in his right arm. Of significance, he had suffered a motor vehicle accident two years prior but had refused medical treatment for the diagnosed right clavicle fracture at that time. On physical examination, patient had ischemic discoloration of his right arm and forearm and was noted to have absent pulses in that arm. CT angiogram of the right upper extremity was performed which showed an occlusion at the thoracic outlet with another obstruction down at the bifurcation of the distal brachial artery at about the level of the antecubital fossa. Embolectomy was initially performed. A EV3 Protege self-expanding stent was deployed within the distal subclavian artery and proximal axillary artery. The stent was postdilated with a EV3 EverCross balloon. Post stenting angiogram did not show any significant residual stenosis. There were no immediate post operative complications. To further investigate etiology of patient's arterial thrombosis, transesophageal echocardiogram was performed that was negative for intracardiac thrombus, however atheromatous plaque lesion was present in aorta and CT angiogram of the chest was recommended for further characterization. CT angiogram of the chest showed new right subclavian artery stent placement with resolution of previous occlusion. Report of CT scan read as such: Stent is patent but buckled proximally with luminal narrowing in the area of buckling. He subsequently underwent examination of the right arm and shoulder under fluoroscopy and showed that the distal segment of the clavicle (due to untreated displaced fracture) impinged on the stent with motion. Interestingly enough, with patient's arm hyperadducted, there was impingement on the subclavian stent, and patient would actually experience numbness in his right arm. As a result, patient underwent operation by orthopedics for right clavicle open reduction internal fixation, and his symptoms of right arm paresthesia was resolved as his stent remained patent without kinking. Conclusions: The incidence of subclavian artery thrombosis is quite uncommon, although this risk is increased with risk factors such as peripheral vascular disease, obesity, and diabetes mellitus. Stent impingement should be on the differential in a patient that is admitting to motional symptoms that is related to the regional blood supply. 110595 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Acute Coronary Syndrome Correlation between Echocardiogram, Catheterization and COVID-19 THIAGO BURIL FONTES1, Rudyney Azevedo1, Maria Gorett W. Matioli1, Regina Adler1, Andre Luis Mendes Martins1 (1) Hospital Servidor Publico Municipal de Sao Paulo Background: Acute coronary syndrome (ACS) is an event that happens because of rupture of an atherosclerotic plaque, leading to ischemia of the heart muscle. The Covid-19 pandemic raised questions related to the increase in the number of infarctions, perhaps due to the destabilization of plaques by the inflammatory substrate. Objectives: To make a correlation between the clinical variables of the presentation, complementary exams such as ECG, echocardiogram and catheterization and the concomitant presentation with Covid-19. Methods: We evaluated 62 patients consecutively admitted with the diagnosis of ACS to a public hospital in Sao Paulo in 2021, during the Covid-19 pandemic. Results: The mean age of the patients was 66.9 years and standard deviation 10,44, 51.6% were men, 66.12% were hypertensive, 33.87% had diabetes, 14.51% had a documented history of coronary artery disease (CAD), 35% with a high risk GRACE score, 6.45% with Covid-19, of which 75% with STEMI. In the ECG, we obtained 11.29% of anterior ischemia, 12.9% of posterior ischemia and 20.96% without alteration. On the echocardiogram, the mean LVEF was 0.57 quantified by the Simpson method, 12.9% of regional change in the anterior wall and 24.19% of the posterior wall. In catheterization, the predominance was involvement of the anterior descending artery with 16.12% and only 3.22% without obstructive CAD. Only one patient with Covid-19 had a normal ECG. Conclusions: In a population treated with the diagnosis of ACS during the Covid-19 pandemic, the prevalence of positive cases was low, however, the incidence of STEMI seems to be high in this population, which denotes greater attention to the care and clinical evolution of these patients. 109893 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Takotsubo Syndrome After Mitral Valve Surgery RAQUEL SILVA BRITO DA LUZ1, Adnaldo da Silveira Maia1, Jhonathan Gouveia da Mota1, Matheus Meirelles1, Mario Issa1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Takotsubo Syndrome is a recurrent diagnosis, however, it's rarely seen post cardiac surgery. The disease usually occurs after physical or emotional stress, most prevalent in post-menopausal women. The clinical features may present similar to acute coronary syndrome, with chest pain and electrocardiogram (ECG) alterations, but with this diagnosis being excluded after the absence of obstructive lesions in coronary angiography and encountering typical echocardiogram findings, such as compensatory apical akinesia and basal compensatory hypercontractility. Case Description: A 56-year-old woman with a history of rheumatoid arthritis, active smoking and percutaneous mitral valvuloplasty in 2007, presents with functional class II dyspnea and transthoracic echocardiogram (TTECO) showing important mitral regurgitation. Patient was submitted to mitral valve replacement surgery with an mechanical prosthesis on March 2022, without complications. In the immediate postoperative care, the patient evolved with cardiogenic shock, requiring vasoactive drugs. The ECG presented with T-wave inversion of precordial leads and TTECO revealed hypercontractility of the basal segments and akinesia of medium-apical segments, with left ventricular ejection (LVEF) of 20%. During hospitalization the patient gradually improved from cardiogenic shock, with normalization of LVEF to 64%. Conclusion: Takotsubo Cardiomyopathy is a reversible condition, characterised by transient ventricular dysfunction, with rare cases described in the context of postoperative care due to valve surgery. The surgical intervention can be considered as a trigger for the development of this syndrome. 109916 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT An Integrative Approach to Elucidate Exercise Intolerance Mechanisms in Heart Failure with Functional Mitral Regurgitation PEDRO CASTILHOS DE FREITAS CRIVELARO1, Felipe Homem Valle1, Willian Roberto Menegazzo1, Anderson Donelli da Silveira1, Nadine Oliveira Clausell1 (1) Hospital de Clinicas de Porto Alegre HCPA Background: Functional mitral regurgitation (fMR) is associated with worse prognosis in heart failure (HF). Furthermore, fMR severity worsening during exercise has been associated with even worse prognosis in this scenario. Report: A 44-year-old female with post-chemotherapy HF and moderate fMR presented with progressive exercise intolerance. To further elucidate mechanisms of exercise intolerance, combined exercise invasive hemodynamic assessment and exercise echocardiography were carried. The procedure was performed by right brachial venous access with exercise at a cycle ergometer. Hemodynamics were evaluated at rest and during progressive incremental exercise, with combined transthoracic echocardiography at both stages. At exercise in a 20 Watts work-load, fMR worsening and increase in pulmonary artery pressures occurred. These findings suggest a potential role of fMR in exercise intolerance. Conclusion: Exercise pulmonary hypertension is associated with worse prognosis in fMR. Whether transcatetheter mitral valve interventions may alter prognosis in this scenario is yet to be determined. We herein present a case of exercise intolerance that is potentially related to fMR worsening during exercise. Our group is prospectively evaluating the role of combined invasive exercise hemodynamic assessment and exercise echocardiography to elucidate mechanisms of exercise intolerance in fMR. 109927 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES ST-Segment Elevation Myocardial Infarction (STEMI) and Pericarditis Epistenocardica Due to Coronary Thrombosis Associated with Cannabis use in a Patient with Low Cardiovascular Risk PEDRO GUIMARAES SILVA1, MELINA DE OLIVEIRA VALDO1, GUILHERME RAPOSO DE MEDEIROS1, MARILIA TAILY SOLIANI1, JOSE CARLOS NICOLAU1 (1) INSTITUTO DO CORACAO DO HCFMUSP Introduction: Certain habits and practices present in groups defined as low risk for cardiovascular disease may be associated with the occurrence of major clinical events, such as acute myocardial infarction (AMI) and stroke. The following report portrays the case of a low-risk patient who suffered from a STEMI followed by pericarditis and whose only risk factor would be recreational cannabis use. Case report: A 35-year-old male with no previous comorbidities or positive family history of cardiovascular disease reported the onset of angina at 03pm on 02/26/2022, only seeking medical attention due to unrelenting thoracic discomfort by 5am on 02/27/2022. He admitted having an average alcohol consumption of 2-3 doses a day on weekends, and a daily cannabis use (up to 10 cigarettes a day), with no use of other drugs in the last 10 years. During assessment, he was in Killip class II and the ECG showed an anterior wall ST elevation, with high sensitivity troponin levels >25000. With the diagnosis of anterior STEMI he was referred to the quaternary reference hospital for a primary angioplasty, where he arrived at midday. The coronary angiography showed significant thrombosis in the proximal segment of the anterior descending artery *(ADA) and a stenosis of approximately 40%. There was also an occlusion in the distal segment, with features suggestive of thromboembolism. Other vascular beds had no lesions whatsoever. Thromboaspiration and angioplasty of the distal segment were performed, without any success in achieving reperfusion. Therapy with intravenous GpIIb/IIIa inhibitor infusion (Tirofiban) for 24 hours was undertaken due to the high thrombotic burden, The next day he evolved with recurrence of severe pleuritic chest pain and underwent a new angiography, with no new findings. Despite that, it was decided to treat the remaining stenosis in the ADA's proximal segment. Subsequent ECGs presented diffuse ST-segment elevation associated with PR segment depression, suggestive of pericarditis epistenocardica. Echocardiographic data showed an ejection fraction of 40% and mild pericardial and pleural effusions. An association of Aspirin + clopidogrel and colchicine 0.5 mg of 12/12h was prescribed for the management of both STEMI and pericarditis. The patient evolved with an inactive electrical zone in the anterior wall and regression of the ST elevation, in addition to a recovery of the ejection fraction (48% on 03/09/22) and lessening of the symptoms. 109910 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Syncope Secondary to Carotid Sinus Syndrome in a Patient with Cervical Mass: A Case Report HELENA ALVES DE ANDRADE RIBEIRO1, Bianca Sarria1, Vanessa Sanson Lani1, Karllayno Camatta Milleri1, Fernando Luiz Torres Gomes1 (1) Antonio Moraes University Hospital (HUCAM) - Federal University of Espirito Santo (UFES) Introduction: Carotid sinus syndrome (CSS) is a complication of head and neck tumors, resulting from baroreceptor hyperexcitation. It was first recognized by Weiss and Baker in 1933, who established the role of this complex. Since then, there have been reports of the association of neck masses related to syncope. The case below describes a patient who presented with symptomatic bradycardia secondary to compression exerted by a neck mass. Case-report: AJBS, 69 years old, female, was admitted to the emergency department with episodes of recurrent syncope, with intensification in the left lateral decubitus position, associated with profuse sweating, nausea, left peripheral facial palsy, and generalized weakness, starting one week before seeking for medical care. She had a large left neck mass and a history of evolution during 20 years, with progressive growth, especially 2 months before the symptomatic condition. The heart rate was 27 beats per minute, in sinus rhythm, with ventricular extrasystoles, with a good response to atropine and venous hydration. Neck computed tomography shows expansive formation with soft tissue density, necrosis, calcification and heterogeneous enhancement, affecting the left parotid, measuring 7.9 x 6.7 x 6.4 cm, with local bulging and parapharyngeal space involvement and multiple lymph node hypertrophy. As an immediate treatment, a transvenous pacemaker was implanted, with subsequent insertion of a definitive pacemaker. This intervention initially showed a positive impact, with heart rate stability, but there was a successive return of hypotension episodes, reaffirming the character of an independent local stimulus caused by the expansive formation. Fine needle aspiration puncture (FNA) of the lesion was performed, with material under analysis. The therapeutic under analysis is local treatment for mass reduction and interruption of the feedback caused by it. Conclusion: SSC caused by the presence of neck masses is due to compression and invasion of the carotid sinus and nerve branches. This syndrome has two subtypes: cardioinhibitory and vasodepressor, and the differentiation is not always clear, since the abnormal stimulation of baroreceptors encompasses different cardiovascular phenotypes. Early diagnosis associated with proper management alters the course and outcomes of this syndrome, mitigating unfavorable outcomes resulting from the condition and having a positive impact on morbimortality. 109912 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Successful Coronary Artery Bypass Graft Surgery After Recent use of Tocilizumab During the Covid19 Pandemic VERONICA HOMEM DE CARVALHO E SILVA1, Joao Pedro Soares Costa1, Yasmeen Salah Mustapha El Qatta1, Victor Marcal Carvalho Mendes1, Alexandre Anderson de Sousa Munhoz Soares2 (1) Universidade de Brasilia (UnB); (2) Cardiologia DASA Hospital Brasilia Unidade Aguas Claras COVID-19 infection triggers a cytokine storm that includes a high expression of interleukin-6 (IL-6). Therefore, anticytokine therapy in patients with acute heart failure associated with SARS-COV2 demonstrated to be a good option of treatment. The case report in question is a case in which the use of tocilizumab with myocardial revascularization was successful. A 48-years-old man with past medical history of obesity, systemic arterial hypertension, type 2 diabetes and non-dialysis chronic kidney disease. Presented with complaints of progressive dyspnea for 10 days, decubitus intolerance and low oxygen saturation. At admission, blood exams demonstrated NT-proBNP 6825 pg/ml, D-dimer 425 ng/mL and creatinine 3,04 mg/dl. Next day, troponin curve was on the rise (519-542-671), which led to the suspicion of myocarditis due to COVID-19. After discussing the risks with the family, he was started on off-label treatment of tocilizumab intravenous, and methylprednisolone 2 mg/kg. Over the next days, exams demonstrated negative RT-PCR, pulmonary congestion on CT (moderate right and small left pleural effusion with restrictive atelectasis and multifocal and bilateral ground-glass opacities), compatible to hypertensive pulmonary acute edema, possibly by myocarditis, therefore tocilizumab and corticoid was suspended and cardiac MRI requested. The MRI resulted in a pattern of inferior and lateral fibrosis suggestive of ischemia, thus coronary angiography was requested. The angiography concluded the presence of severe coronary atherosclerotic disease with a three-vessel pattern, indicating the need of myocardial revascularization surgery. Due to the immunosuppression that tocilizumab causes, the infectious disease team was consulted to discuss the risks/benefits of delaying the surgery, it was agreed that it would be after the half-life of the product, which is 11 to 16 days. The surgery took place without complications. After surgery, the patient needed to use norepinephrine, dobutamine and vasopressin, reacting well to the treatment. After the episode, he spent another 9 days in the ICU with hemodialysis as his chronic renal disease worsened but quickly recovered, without other noteworthy complications, being discharged after the period. We report the successful myocardial revascularization surgery after the use of tocilizumab without any infectious complication. The surgery schedule after the half -life period may be considered to the treatment of this complication. 109961 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Recurrence of Spontaneous Coronary Artery Dissection in a Puerperal Woman with COVID-19 VICTOR ALEXANDRE DOS SANTOS VALSECCHI1, Paula Santiago Teixeira1, Thalita Ruolla Barros1, Marcos Damiao Candido Ferreira1, Adriano Caixeta1 (1) Universidade Federal de Sao Paulo Introduction: Spontaneous coronary artery dissection (SCAD) is more common in women, aged approximately 50 years. It accounts for approximately 15-20% of myocardial infarctions (MI) during pregnancy or the peripartum period. It is still a disease of unknown cause, but it is related to triggering factors such as emotional stress and pregnancy. Objective: To report a case that occurred in a university hospital and emphasize the diagnostic importance. Case Report: E.L.A., 36 years old, female, hypertension during a previous pregnancy. Three months ago during gestational period and infection by Influenzae presented coronary syndrome without ST-segment elevation (NSTEMI). Catheterization showed spontaneous coronary dissection of the anterior descending artery and circumflex both classified as Saw type 2 with conservative treatment. The patient was admitted in the third postoperative day of a cesarean section due to atypical chest pain. Electrocardiogram showed T-wave inversion in DI, AVL, V5 and V6. The curve of markers of myocardial necrosis was negative and COVID-19 was positive. Echocardiogram (ECO) without segmental dysfunction. During hospitalization for NSTEMI patient evolved with a new episode of chest pain and dynamic alteration of the ST segment. Catheterization showed new focal spontaneous dissection in the distal third of anterior descending artery and first diagonal dissection in all its extension, both with Saw type 2 classification. Improvement of circumflex and right coronary artery free of stenosis. In view of hemodynamic instability, coronary angioplasty of the LAD was performed with 1 drug-eluting stent, with angiographic success. The patient evolved with improvement of symptoms. New ECO showed anterior apical and septal apical akinesia. Conclusion: It is critical that in young women with chest pain, SCAD is suspected because it is an underdiagnosed disease. Accurate and rapid diagnosis is paramount as the management of MI caused by SCAD differs from that of an atherosclerotic cause. 109964 Modality: E-Poster Young Researcher - Case Report Category: CARDIO-ONCOLOGY Combined Heart-Kidney Transplantation in Congestive Heart Failure in Onco-Cardiology AMANDA DE ANDRADE CAMPELLO GIROTTO1, Luisa Wagner do Rego Barros1, Juliana dos Santos Macaciel1, Jacqueline Sampaio Miranda1, Antonio Fatorelli1 (1) Instituto Nacional de Cardiologia Introduction: Heart transplantation is the definitive therapy for eligible patients with end-stage heart failure. This subgroup of patients often develops with concomitant kidney injury and, in this context, treatment options become limited. Combined heart and kidney transplantation is a growing practice in recent years in large centers, with increasingly promising results. Case Report: L.R.G, female, 22 years old, born in Rio de Janeiro, with dilated cardiomyopathy secondary to anthracycline cardiotoxicity, being followed up for heart failure with reduced ejection fraction with good functional class. Refers progression of the condition 3 months after pregnancy, when she started to present dyspnea on minor exertion. In use of Carvedilol 50 mg, Sacubitril/Valsartan 98/103 mg 2x, Spironolactone 25 mg, Furosemide 80 mg. Undergoing CPET: VO2 10.7|VEVCO2 36.3|R: 1.17, being referred for evaluation of heart transplantation. Loss of outpatient follow-up in the following months, when developed osteomyelitis in the left lower limb prosthesis, and the need to use broad-spectrum antibiotics. She presented Acute Kidney Injury with evolution to daily hemodialysis. Clinical intractability and need for transfemoral limb amputation were defined. She maintains anuria and anasarca despite dialysis therapy, with the need for inotropes for clinical compensation. Dobutamine was started for type 2 cardiorenal component test, with partial response. SHe evolves with clinical stability on INTERMACS III, with improvement of anasarca. After discussion in the Heart Team, was opted for a combined heart and kidney transplant. Submitted to the procedure on 06/22/21. She was discharged from the hospital with satisfactory diuresis and preserved systolic function. Conclusion: The clinical case reinforces the importance of clinical identification of patients with signs of advanced heart failure, to refer them as soon as possible to specialized centers, with early treatment being an important prognostic marker. Combined heart transplantation is a worldwide trend approach, and this strategy is increasingly used in relation to the sequential transplantation strategy (kidney after heart). The database is still limited and has some retrospective studies, highlighting the importance of new studies with high scientific rigor to guide complex cases. 109969 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Case Report: Post-Acute COVID-19 Myocarditis and Long-Term Effects on Reduced Functional Capacity BRUNO LINHARES AZEREDO CORREA1, Fabio Lucas Bassini e Silva1, Jaime Lobo FIgueiredo1, Renata Rodrigues Teixeira de Castro1, Fabio Akio Nishijuka1 (1) Hospital Naval Marcilio Dias Introduction: COVID-19 infection has become a multiorgan disease, which is already well documented in the literature. 2 years after the beginning of the pandemic, we are knowing the long-term effects. As if that wasn't enough, vaccines against COVID-19 still had important side effects on the cardiovascular system. Objective: The objective of this report is to discuss the chronic cardiological form of COVID-19, its pathophysiological mechanisms and propose ideas for an approach. Case report: A 30-year-old male, physically active and without comorbidities, with confirmed COVID-19 infection at the end of 2020 and in August 2021, both with a mild condition, was hospitalized with acute myocarditis in September 2021. 3 weeks after discharge, he received SARS vaccine -CoV-2 (Pfizer), when the chest pain intensified, becoming daily. Hospitalized in November 2021 for tachycardia associated with lipothymia. Investigated with 24-hour holter that did not demonstrate arrhythmias and exercise test without criteria for ischemia. Magnetic resonance imaging showed worsening of mesocardial enhancement from 2% (Sep21) to 4% (Jan22) and edema. At follow-up, he presented with progressive dyspnea on exertion with intolerance to physical exercise, in addition to atypical chest pain that led to several visits to the emergency, attributed to chronic pericarditis. In March 2022, he performed an exercise stress test reaching 10.2 METS, and an echocardiogram with strain, without changes in function or contractility. This is why this service referred the patient to cardiac rehabilitation in order to improve functional capacity. Conclusion: Understand the pathophysiological mechanisms and develop strategies to mitigate the chronic and/or late cardiological effects of COVID-19. The symptoms of long-COVID cause multiple emergency visit, in addition to several exams that financially burden the patient and the health system. Similar cases could generate an unprecedented impact on the functionality of the economically active population. 109979 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Extrinsic Compression of the Left Main Coronary Artery Secondary to the Common Atrium VITOR BONIATTI NEVES1, Deborah Valente Ramos Rocha1, Vitor Boniatti Neves2, Juan Tiago Nunes Pagnussat1, Tiago Vendruscolo3 (1) Universidade Federal da Fronteira Sul - RS; (2) Faculdade IMED - RS; (3) Instituto do Coracao de Passo Fundo - RS Introduction: Common atrium is characterized by complete absence of the interatrial septum, the presence of small strads of tissue presente at the superior atrial wall of the common chamber, absence of interventricular communication and accompanying atrioventricular cushion defect. Objective: Present a report of a rare case of interatrial communication with absence of interatrial septum and complications. Case Report: N.R.M.O, 54 years old, female. Hypertensive and chronic obstructive pulmonary disease. Arives at the emergency room with precordial pain for 1 year, worsening in the last 5 days, associated with dyspnea. Management for acute coronary syndrome was initiated and the patient was referred for invasive stratification. Physical examination: regular rhythm, 2 clicks, systolic murmur 3/6+ at pulmonary focus. Oxygen saturation: 88%. Digital clubbing, but labial cyanosis at rest was not observed. Laboratory data revealed an elevated ultrasensitive troponin - 1941. Electrocardiography: showed left atrial overload. Echocardiogram; complete absence of the interatrial septum. The right ventricle was markedly enlarged with mild pulmonary hypertension (estimated right ventricular pressure, 68 mmHg). Coronary cineangiography demonstrated a LMCA with moderate/severe proximal lesion. An angiography of the ostial left main coronary artery for probable extrinsic compression of the pulmonary artery was performed (IVUS) for anatomical evaluation of significant luminal reduction. The first measurement identified a minimum luminal area of 8.77 mm2, without evidencing atherosclerotic disease. The heart team still discussing the therapy plain. Conclusion: The difficult diagnosis, which begins with investigation of other pathologies, leads to clinical and myocardial worsening of the patient. In the case of this patient, the common atrium led to pulmonary hypertension, with significant dilation of the pulmonary artery, causing extrinsic compression of the left coronary trunk. There are few case reports of older patients with such condition and the therapeutic approach still a challenge. 110038 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Eosinophilic Cardiomyopathy Secondary to Chemotherapy: A Case Report ADOZINA MARQUES DE SOUZA NETA1, Victor Agueda Salles1, Luciana da Rocha Ferreira Lobbe Cotta1, Bruno Miranda Marques1, Jacqueline Sampaio dos Santos Miranda1 (1) HOSPITAL COPA STAR Hypereosinophilic syndrome (HES) is rare and defined as blood eosinophil count >1.5 x 109/L and eosinophilia-related organ damage. According to Mankad et al. in 2015, the heart is an affected organ with an incidence of up to 50% of cases. HES, it is classified into hereditary, undetermined significance, primary (clonal/neoplastic) and secondary (reactive) variants. Diagnosing and stratifying the disease is essential to start treatment at an early. Male patient, 65 years old, with dyspnea and with pulmonary congestion for three weeks. Previous history of lymphoproliferative disease, Waldenstrom's Macroglobulinemia, treated with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab R-CHOP in 2013. In 2018, due to disease progression, he used R-bendamustine + lenalidomide 6 cycles ending 04/15/2019. Currently in remission. Previous lab history of leukogram with eosinophilia ranging from 19.1% on to 47.3%. He sought the emergency department with a picture of decompensated heart failure, associated with elevated troponin and BNP, being referred for coronary angiography, which showed no significant coronary artery disease, however, ventriculography with left ventricular tip obliteration. In the 48 hours after admission, the patient hemodynamic instability, requiring inotropes and mechanical ventilation. Leukogram with eosinophil of 1,160/mm3 (10%). Cardiac NMR imaging showed mild myocardial fibrosis and left ventricular apex occupied by solid content. With the possibility of HES, he underwent pulse therapy with 1g methylprednisolone for 3 days and underwent surgery to remove the mass from the left ventricle. The histopathology of the material showed a fibrin thrombus with numerous eosinophils, thus confirming the SHE. Faced with the possibility of recurrence of the lymphoproliferative disease, a bone marrow biopsy was performed to rule out the presence of B lymphocytes and a negative karyotype for the FIP1L1-PDGFRA mutation. Hereditary causes and reactivation of the neoplasm were ruled out, it confirms the hypothesis of SHE secondary to chemotherapy. The patient evolved with recovery of ventricular function and he was discharged from the hospital with corticosteroids and anticoagulation. In view of this report, the importance of performing routine echocardiography in patients with persistent eosinophilia is evident, given the high prevalence of cardiac involvement in HES. Early diagnosis and treatment improve quality of life reduce mortality. 110055 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 and Primary Angioplasty: Importance of the Door-to-Balloon Time ARGILA GONCALVES DE CARVALHO SANTANA1, Argila Goncalves de Carvalho Santana1, Patricia Veiga Nascimento1, Simone Leticia Souza Querino3, Thayna Oliveira Militao1 (1) Universidade Federal do Reconcavo da Bahia; (2) Hospital Ana Nery; (3) Universidade Federal da Bahia Background: Covid-19 infection exposes patients to several complications, including a greater predisposition to Acute Myocardial Infarction (AMI). Thrombotic complications occur as a result of the inflammatory process, triggering platelet activation, endothelial dysfunction and stasis. Objective: To report a case of a young patient, with no associated comorbidities, with ST-segment elevation AMI who underwent Primary Angioplasty. Methods: Retrospective study research, based on chart analysis, case study type. Case report supported by the Ethics Committee with CAAE 44553421.0.0000.0056. Results: Patient, 45 years old, male, black, general services assistant, smoker and without other previous comorbidities, complaining of fever, malaise associated with 5 days, taking the 2nd dose of the vaccine against SARs CoV2 - Oxford even 2 days ago showing typical symptoms of Covid-19 infection. On the morning of 07/18 at 5:30 am, he presented oppressive chest pain associated with upper limb paresthesia, without respiratory distress. Admitted to the hemodynamics of the HAN on an emergency basis at 09:40h, coming together with the SAMU, TR for SARS CoV2 negative, ECG performed with supra inferior wall, V3R, V4R, triggered AMI protocol, performed 300 mg of ASS, 600 mg of clopidogrel and morphine 2 mg. Undergoing coronary cineangiography and primary angioplasty: Right Coronary Artery with 100% lesion in the middle third by a thrombus. At the end of the procedure, there was good angiographic appearance of the treated arteries, TIMI 3 flow. Echocardiogram: Simpson EF: 42%, with segmental alteration: Akinesia of the basal and middle segments of the inferior and inferoseptal walls. The patient evolved without complications and was discharged after 2 days of hospitalization. Conclusion: Despite a door-to-balloon time of 4h10min, due to the prolonged ischemia time and high thrombotic load, although asymptomatic, the patient evolved with left ventricular segmental dysfunction, which demonstrates that "time is myocardium". 110067 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Embolic Myocardial Infarction Due to Aortic Valve Infective Endocarditis Complication in a Previously Healthy Young Patient ANANDA RIBEIRO FRETES1, Matheus Lima Lula Guimaraes1, Paula Maria Pinheiro Miranda1, Leticia Aparecida Braga da Silva1 (1) Universidade Federal do Mato Grosso Introduction: Coronary artery embolism is an uncommon cause of acute myocardial infarction and one of the most important causes of non-atherosclerotic ST-segment-elevation myocardial infarction. The most common causes are: Infectious Endocarditis (IE), Atrial Fibrillation and Prosthetic Heart Valve Thrombosis. Case Report: Patient, 24 years old, male, smoker, alcoholic, with no previous diagnosed pathologies, with moderate intensity retrosternal pain in the last 30 days, dyspnea on moderate exertion, daily fever, sweating, chills and weight loss of 7 kg in the period. Admitted to an emergency care unit with significant worsening of severe retrosternal pain, worsening with exertion and associated with dyspnea on minor exertion. Physical examination showed an abscess in the left upper molar, cardiac auscultation with a more audible systolic murmur in a 4+/6+ aortic focus radiating to the carotids. The electrocardiogram showed ST-segment elevation in V2, V3, V4, V5 and V6 and troponin: 210 (reference value: <0.03). After 5 hours of evolution, catheterization was performed demonstrating left anterior descending artery (LAD) occluded in the middle third, right coronary artery and circumflex coronary artery free of obstructive lesions, followed by primary angioplasty with implantation of 01 drug-eluting stent in the LAD. An echocardiogram was performed with evidence of vegetation in the aortic valve and an image of paravalvular abscess. Infective endocarditis was confirmed with initiation of antibiotic therapy. Subsequently, during the same hospitalization, aortic valve replacement surgery was performed with implantation of a metallic prosthesis, correction of paravalvular abscess with a pericardium flap and enlargement of the aortic root. The patient evolved in the postoperative period without intercurrences, being discharged after the end of antibiotic therapy, with resolution of the previously presented complaints. Conclusion: Embolic myocardial infarction is a rare but increasingly recognized complication of infective endocarditis and it has increased risk of heart failure and a high mortality rate. Septic embolization resulting in acute coronary syndrome has an incidence of 2.2%. It should be suspected in young patients with a diagnosis of endocarditis or suggestive clinical signs. 110223 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Carcinoid Heart Disease: A Condition to Remember in Cases of Right-Sided Heart Failure DOUGLAS BORGES DA COSTA FILHO1, Euton Freitas de Castro Junior1, Ana Carolina Brito de Alcantara2, Danielli Oliveira da Costa Lino3, Ane Karoline Medina Neri4 (1) Universidade Federal do Ceara, Hospital Universitario Walter Cantidio; (2) Hospital Geral Dr. Waldemar de Alcantara; (3) Hospital de Messejana Dr. Carlos Alberto Studart Gomes; (4) Universidade de Fortaleza, Postgraduate Program in Collective Health Introduction: Although uncommon, carcinoid heart disease is one of the main causes of morbidity and mortality in the context of carcinoid syndrome and can occur as the initial presentation of this neuroendocrine tumour. Among the cardiac impairments are the thickening of valves and right chambers due to infiltration of the parenchyma by carcinoid plaques and the high circulating concentration of serotonin, which can lead to severe dysfunctions. The aim of this study is to share a case series of individuals with carcinoid heart disease and to discuss the main clinical features related to this condition. Case Report: Three cases of carcinoid heart disease were treated in reference hospitals in Cardiology in the city of Fortaleza, state of Ceara, Brazil. The patients were female, were in adulthood, had intestinal carcinoid tumor with liver metastasis, presented with tricuspid valve involvement and a clinical presentation of right-sided heart failure (HF) at diagnosis. The first patient, a 59-year-old female, had insufficiency of the tricuspid and pulmonary valves with the latter also presenting stenotic lesion demonstrated by transthoracic echocardiography (TTE). The second patient, a 48-year-old woman, sought medical assistance complaining of gastrointestinal discomfort. A neuroendocrine tumour was diagnosed in the terminal ileum, with secondary lung implants. TTE showed a tricuspid valve with thickened leaflets, reduced mobility, moderate regurgitation and mild stenosis. The third patient, a 55-year-old female, sought an evaluation complaining of abdominal discomfort and cervical and facial flush. She was diagnosed with a well-differentiated neuroendocrine tumour in the colon and a TTE showed a tricuspid valve with thickened leaflets and mobility restriction with significant coaptation failure and torrential tricuspid insufficiency. Conclusions: This study reported the cases of three patients with carcinoid syndrome with heart involvement, describing their main clinical presentations and aspects in common between them, such as female gender, adulthood, the presence of intestinal carcinoid tumor with liver metastasis, tricuspid valve involvement and a clinical presentation compatible with right-sided HF. Despite being infrequent, carcinoid heart disease deserves attention and should generally be screened for among patients with carcinoid tumors, especially in those individuals who present with a condition compatible with right-sided HF. 110330 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Carfilzomib as a Cause of ST-Segment Elevation DANIELA BARBOSA MATEUS1, Antonio Carvalho1, Rita Gomes1, Rita Duarte1, Carlos Rabacal1 (1) Hospital Vila Franca de Xira - Portugal Introduction: Chemotherapeutic agents, especially proteasome inhibitors, used in the treatment of Multiple Myeloma, have a high risk of cardiovascular disease. The authors report a case of ST-segment elevation secondary to vasospastic angina resulting from the use of carfilzomib. Case Report: 63-year-old man, melanodermic, with a personal history of IgG lambda multiple myeloma diagnosed in February 2012 (stage IIA), under chemotherapy with carfilzomib 120 mg weekly, since May 2021. Admitted in the emergency department due to retrosternal pain with left upper limb irradiation, which started at rest, ten hours prior to presentation. Hemodynamically stable, with an unremarkable physical exam. Initial investigation revealed: electrocardiogram with sinus tachycardia, ST elevation (>2 mm from point J) in V2-V4 with hyperacute T waves; echocardiogram with hypokinesia of the apex and apical segments of the septum, anterior wall and inferior wall; preserved systolic function; non-dilated cardiac chambers; valve structures without morphofunctional changes. The patient was transferred to a center of emergency cardiac catheterization. The coronary arteries presented no angiographically apparent lesions; ventriculography revealed good ventricular function with apical hypokinesia and functional study of the anterior descending artery demonstrated reactivity to acetylcholine, favoring the diagnostic hypothesis of epicardial coronary vasospastic angina. Subsequently, analytically, troponin I (high sensibility) was 5,4 pg/mL, reaching a maximum value of 58 pg/ml. Vasospastic angina secondary to carfilzomib was assumed. Vasodilator therapy was started with good clinical evolution, without recurrence of angor and and maintaining the previously described electrocardiographic changes. Discussion: The authors intend to alert to the harmful cardiovascular effects with the use of chemotherapeutic agents, in this case carfilzomib. 110267 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Don't be Blinded by an Obvious Diagnosis - Pulmonary Hypertension with Multifactorial Mechanisms BRUNO GONCALVES GARCIA1, Thaissa Santos Monteiro1, Fabio Akio Nishijuca1, Jamili Zanon Bonicenha1, Maria Carolina Terra Cola1 (1) National Institute of Cardiology (INC) - Rio de Janeiro, Brazil Introduction: Atrial septal defect (ASD) is a congenital heart disease (CHD) in which blood flows between the atria, primarily with a left-right shunt leading to pulmonary hyperflow and right ventricle (RV) volume overload and consequently pulmonary hypertension (PH) type I and RV enlargement and dysfunction. Eisenmenger syndrome occurs when, because of the PH and RV dysfunction, the shunt flow turns right-left and cyanosis appears. However, there are many other causes for PH, which is classified by 5 different types. Case Report: Female patient, 41 year-old, with low educational level, former smoker and history of asthma, was referred to an adult CHD center after being initially diagnosed with ASD with Eisenmenger syndrome. The patient had clubbing and central cyanosis, a palpable RV and systolic murmur in the tricuspid focus. Echocardiogram identified RV dysfunction, bidirectional shunt in the interatrial septum, tricuspide valve regurgitation, pulmonary artery systolic pressure of 128 mmHg and significant enlargement of the pulmonary artery (PA), with thrombus in situ. Although there was a shunt in the interatrial septum, the ASD observed was small. Angiotomography of the pulmonary arteries confirmed bilateral chronic thromboembolism. Rheumatological assessment was negative, as well the thrombophilic panel. Late syphilis was diagnosed by antitreponemic antibody, and treatment was instituted. PA catheterization was not performed due to risk of distal embolization of thrombus present in the PA. The heart team concluded it was a multifactorial PH, including type I and type IV. Syphilitic arteritis of the PA was also remembered, but could not be confirmed. Closure of the ASD was considered contraindicated because of the PH, and anticoagulation was initiated as well as sildenafil, and the patient followed with improvement of oxygen saturation and exercise capacity. Conclusion: Facing a patient with PH and a late diagnosis of ASD, could have mislead to the conclusion of this being a case of PH type I with Eisenmenger syndrome purely. ASD is one of the most common cause of adult CHD, as there are other common causes for PH. One should not be blinded by the combination of both, and a thorough assessment should be done to insure there is indeed a cause-and-effect relationship. 110369 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Systemic Fibrinolysis for Treatment of Obstructive Shock in a Patient with Aortic Bioprosthetic Valve-in-Valve Thrombosis JIAN CHU1, Nikitaa Nath1, Natasha Rana2 (1) Rush University Medical Center, Department of Internal Medicine; (2) Rush University Medical Center, Department of Internal Medicine, Section of Cardiology An 81-year-old man with ischemic heart failure and aortic valve-in-valve bioprosthesis presented with acute dyspnea. On exam, he was afebrile, but hypotensive, tachycardic, and tachypneic. Labs were notable for a BNP of 3056 pg/mL and venous lactate of 2.1 mmol/L. Due to suspicion for cardiogenic shock, he underwent emergent cardiac catheterization, which revealed elevated left cardiac filling pressures. He was started on inotropes and vasopressors with placement of an intra-aortic balloon pump. A transthoracic echocardiogram showed a LV ejection fraction of 10-15% and prosthetic aortic valve dysfunction with a peak velocity of 3.7 m/s and mean gradient of 32 mm Hg (markedly higher than baseline). A 9 x 17 mm echodensity was seen on the valve leaflet consistent with bioprosthetic valve thrombosis (BPVT). After multidisciplinary discussion with cardiothoracic surgery and interventional cardiology, he was administered systemic tissue plasminogen activator with a 10 mg load followed by 40 mg over 4 hours. Within 24 hours, he was able to wean off all pressors with improved echocardiographic parameters. The data behind fibrinolysis for aortic BPVT is largely derived from the PROMETEE study, which supports ultraslow fibrinolysis and the present case shows that faster infusions may be safe and effective in decompensated patients. However, more data is needed to guide choice of surgical vs. non-surgical management of patients with decompensation from BPVT. 110485 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Infectious Tricuspid Valve Endocarditis and Septic Pulmonary Embolism in a Young Male with Suspected Antiphospholipid Syndrome ADRIANO LOPES BATISTA1, Gracylma Guimaraes Rocha1, Ingrid Loureiro de Queiroz Lima1, Marlucia do Nascimento Nobre1, Augusto de Carvalho Bezerra3 (1) Hospital Universitario Getulio Vargas - HUGV; (2) Universidade Federal do Amazonas - UFAM; (3) Hospital Universitario Francisca Mendes - HUFM Antiphospholipid syndrome is an autoimmune disease characterized by recurrent episodes of vascular thrombosis, predominantly in females. Infective endocarditis associated with this disease is uncommon, with more prevalent aseptic endocarditis. However, there is potential for this collagenosis to lead to pulmonary hypertension, which in turn causes cardiac dysfunction in the right chambers, predisposing the endocardium to infection and, consequently, the lung to septic embolism. The case report is of a 23 years-old male with a clinical history since adolescence of recurrent deep venous and arterial thrombosis, lower limb edema, and progressive dyspnea. Eight years after the onset of symptoms, he developed a condition of digestive hemorrhage associated with thrombocytopenia where, during blood product transfusion, he showed signs of bacteremia. Since then, daily, with mild symptoms of chills, low-grade fever, sweating, arthralgia, and progressive worsening of dyspnea. After 30 days, the patient evolved with pulmonary focus septic shock and was then transferred to our hospital. Chest tomography showed nodules with necrosis and central cavitation compatible with septic emboli(1). Echocardiography showed dilatation of the right chambers, significant pulmonary hypertension, insufficient tricuspid valve, perforated, and a mobile vegetative lesion measuring 1.7 x 1.4 cm adhered to the anterior leaflet compatible with endocarditis. He received antibiotic therapy and valve replacement surgery. All collected blood cultures since admission were negative. We are not aware of cultures performed at the hospital where he came from. He was discharged from the Intensive Care Unit (ICU) and was awaiting the results of investigative tests for the underlying thrombogenic disease. Suddenly, he presented dyspnea and chest pain, evolving into cardiac arrest due to pulseless electrical activity resulting in death. After death, we received the tests that were positive for Antiphospholipid Syndrome. However, for the definitive diagnosis of this collagenosis, the antibodies must remain positive after 12 weeks of the first collection. 110493 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Adverse Effect of Vaccination for COVID-19: Myocarditis Case Report FELIPE MONGE TEIXEIRA1, Paulo Vitor da Silva Goncalves1, Diego Bianchi Braga Campos1, Marcelo Imbroinise Bittencourt1, Ricardo Mourilhe Rocha1 (1) Cardiology Service - Pedro Ernesto University Hospital - UERJ Introduction: In 2020, the WHO declared COVID-19 a pandemic. In the same year, the US Food and Drug Administration (FDA) granted emergency use authorization for the Pfizer/BioNTech and Moderna vaccines. Despite the benefits of vaccination, it can also pose potential risks such as myocarditis. Case Report: Female, 37 years old, without comorbidities, denies alcohol consumption, smoking, and recent infections. She presented mild COVID in January 2021, and after 7 months, she was vaccinated with 2 doses of Pfizer/BioNTech. After vaccination, she developed oppressive type A chest pain, VAS 8/10, radiating to the left upper limb and nausea, seeking emergency care. An ECG was performed, without significant changes, but with high ultrasensitive troponin values (12,500|RV < 5), motivating his hospitalization. She underwent transthoracic echocardiography (TE), which demonstrated septo-apical hypokinesia with preserved function. Coronary angiography was performed on the first day after admission, which showed no obstructions. She had a laboratory with still high troponin, but falling, in addition to a negative PCR for COVID. A new TE was performed, which showed no segmental lesions or changes. Cardiac resonance imaging was requested, demonstrating moderate myocardial fibrosis (11%) suggestive of myopericarditis, as shown in Figures 1A and 1B. In view of this, he started treatment with colchicine and ASA, which led to a drop in troponin after 7 days of hospitalization, and he was discharged asymptomatic. Conclusion: Vaccination for COVID-19 continues to be recommended for all people, clearly outweighing the risks in all populations. As observed in the case described, most individuals with myocarditis had a full recovery of ventricular function, with few reports of major complications. 110515 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Echodopplercardiography as a Marker of Malignancy in Intracardiac Tumors: Case Report VINICIUS STEFANO BARROS DA ROCHA1, Anita de Oliveira e Souza Fragoso1, Maria Luciana Zacharias Hannouche da Trindade2, Ana Clara Tude Rodrigues1 (1) Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP); (2) Instituto de Radiologia do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (InRad) Introduction: Leiomyosarcoma is one of the most common malignant tumors among retroperitoneal tumors, corresponding to approximately 15% of these. Involvement of the inferior vena cava (IVC) and right heart chambers is rare and related to a worse prognosis. Ultrasound-enhancing agent echocardiography (ECHO with enhancement) has been used to identify intracardiac tumors with high accuracy. However, this exam may eventually present limitations in relation to the definition of malignancy. Case Report: A 53-year-old female patient with diabetes and dyslipidemia sought medical care with left low back pain for about 5 months, associated with bulging in the right flank region and weight loss of 5 kg. Investigation with computed tomography (CT) of the abdomen from an external service showed a retroperitoneal mass in the IVC and right atrium (RA), and the biopsy with guided puncture was compatible with high-grade leiomyosarcoma. The enhanced echo showed partial perfusion of the mass in the RA, while the three-dimensional transesophageal echocardiogram showed a heterogeneous multilobulated mass extending from the most apical portion of the IVC to the RA, close to the tricuspid valve, with vacuolar areas in its interior, both tests suggesting a benign process. The patient was scheduled for vascular and cardiac surgery for definitive treatment. Conclusion: Despite studies showing good accuracy of echocardiography with enhancement for differentiating between malignant and benign tumors, according to the characteristics of the perfusion, malignant tumors with necrotic process inside them, such as leiomyosarcomas, may present with partial perfusion of the tumor, limiting the accuracy of the method. 110539 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Uncommon Presentation of Arterial Thrombosis in a Young Male with Systemic Lupus Erythematosus GABRIEL RIBEIRO ROSA1, Elisa Carolina de Almeida Negrello1, Alcirley de Almeida Luiz1, Pedro Henrique Bonifacio Shiino1 (1) Hospital Universitario do Oeste do Parana (HUOP) Introduction: Systemic lupus erythematosus (SLE) is associated with severe cardiovascular manifestations, including myocardial infarction (MI), which is an important cause of premature mortality and morbidity. Accelerated atherosclerosis is the main mechanism involved. We report a case of a young male with an acute MI with ST segment elevation, secondary to coronary thrombosis, which led to the diagnosis of SLE-associated antiphospholipid syndrome (APS). Case Report: A 24-year-old male was admitted to the hospital with typical chest pain, lasting 6 hours. The electrocardiogram in the emergency room (ER) showed ST segment elevation in the anterior wall. The patient had a history of SLE, which was diagnosed when he was 15 years old, and was undergoing investigation for APS due to the positivity of IgG anti-b2 glycoprotein-1 antibody. He had traditional risk factors, such as hypertension and class I obesity. He received treatment in the ER and was referred to Interventional Cardiology. A coronary angiogram showed complete occlusion proximally in the left anterior descending artery. A percutaneous angioplasty with no stent was performed, due to angiographic signs of thrombosis without associated atherosclerotic disease in other vessels. The patient had a good recovery without other complications. Conclusions: SLE is an autoimmune disease commonly associated with APS. This association increases mortality, and the positivity of antiphospholipid antibodies in SLE patients' serum is an independent risk factor for premature death. Deep venous thrombosis and stroke, differently than the reported case, are the most common cardiovascular events in these patients. 110546 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Post-Infarction Left Ventricular Pseudoaneurysm Treated with Percutaneous Transcatheter Occlusion: A Case Report ISABELA GALIZZI FAE1, Carolina Kuchenbecker Soares1, Luis Henrique Coelho Pinto1, Fernanda Araujo Sa1, Anderson Ferreira Leite1 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais Introduction: Left ventricular (LV) pseudoaneurysm is a rare complication after myocardial infarction (MI) characterized by rupture of the LV wall contained by pericardium, thrombus or scar tissue. If not treated properly, it can lead to cardiac tamponade and death. We aim to describe a case of LV pseudoaneurysm after MI treated with percutaneous closure. Case Report: A 57-year-old man presented with chest pain and extensive anterior ST-segment elevation with right bundle-branch block. Acute MI protocol and thrombolysis was performed, without reperfusion criteria. Rescue angioplasty was not available that day. Cineangiocoronariography in the next day revealed severe occlusion (90%) in descending artery (DA) ostium, so angioplasty with pharmacological stent in the left main artery (LMA) towards DA was performed. Echocardiogram showed ejection fraction of 38%, segmentary defect of contractility and an image suggesting pseudoaneurysm in apex of LV, which was confirmed in cardiac resonance and angiotomography. The opted approach was percutaneous transcatheter closure due to high risk of rupture. Surgery was dismissed, as the patient was clinically stable and had elevated risk surgery, owing to MI and recent angioplasty to LMA towards DA. An interatrial communication prosthesis was implanted, without any flow inside the pseudoaneurysm orifice. The patient remains asymptomatic after six months of follow-up. Conclusion: High suspicion is required for the diagnosis of post-infarction LV pseudoaneurysm. Non-invasive imaging is indispensable in stable patients. Surgical treatment is usually recommended, notwithstanding, percutaneous transcatheter closure is growing in importance as it has lower morbimortality compared to surgery, with multiple successful case reports being described. 110790 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Coronary Fistula, Right Ventricle Epicardial Pseudoaneurysm and Acute Myocardial Infarction - "Three in a Row" JULIANA JANGELAVICIN BARBOSA1, Otavio Augusto Oliveira de Carvalho1, Thiago Abizaid Kleinsorge1, Ruldney Ray dos Santos Oliveira1, Antonio Tito Paladino Filho1 (1) Hospital SEPACO (SEPACO) Introduction: Coronary artery fistula (CAF) is a rare abnormality characterized by the connection between one or more coronary arteries and a cardiac cavity or great vessel. Depending on several factors can present without clinical repercussions or cause significant hemodynamics complications. Case description: A 33-year-old male patient presented with chest pain and ST-segment elevation in leads DII, DIII and aVF at the ECG. Troponin was elevated (Pocket). Referred for urgent cardiac catheterization, we not identify obstructive coronary lesions, but observed the presence of a fistula with extravasation of contrast into a neo-cavity. Cardiac magnetic resonance imaging was performed with findings suggestive of acute myocardial infarction (AMI) in the inferior wall and a "mass" adjacent to the right atrium with an image of a thrombus in its interior. The investigation was complemented with coronary CT angiography, bringing the hypotheses of a pseudoaneurysm and evidencing the feeding origin from the right coronary fistula. This "mass" exerted a compression effect on the right coronary artery (RCA), resulting in inferior wall infarction. The patient was referred for surgical intervention, confirming the hypotheses of a right ventricular (RV) pseudoaneurysm with a thrombus inside it. Conclusion: The diagnosis of CAF is rare, and in the clinical case, it was responsible for the formation of a pseudoaneurysm that expanded, evolving with AMI due to compression of the RCA. The case brings together other findings - CAF and RV epicardial pseudoaneurysm - which, despite being rare, presented with a common condition in cardiac emergencies: AMI. Advances in cardiovascular imaging contribute in such types of clinical cases with early diagnosis and effective management, leading to favorable clinical outcomes. 110810 Modality: E-Poster Young Researcher - Case Report Category: CARDIO-ONCOLOGY Case Report: Ventricular Dysfunction Associated with Pazopanib LAISSE BARRETO FERREIRA REIS1, Maira de Melo Ibrahim Nogueira2, Valmir de Freitas Costa1, Rafael Alves da Silva1, Douglas Celestino Froes3 (1) Instituto do Coracao/FMUSP; (2) Hospital Felicio Rocho; (3) Centro Hospitalar do Municipio de Santo Andre Introduction: Pazopanib is a tyrosine kinase inhibitor whose main therapeutic targets are PDGF (platelet-derived growth factor) and, mainly, VEGF (endothelial growth factor). Its use in oncology is in the treatment of renal cell carcinoma, sarcomas and, less commonly, thyroid cancer. This medication has arterial hypertension as its main cardiovascular side effect, but it can also cause arrhythmias, QT interval prolongation and heart failure. Case description: A 64-year-old patient with a personal history of arterial hypertension, dyslipidemia and non-insulin-requiring diabetes, had no history of heart failure and had an echocardiogram with a left ventricular ejection fraction of 60%. Diagnosed with non-metastatic renal cell carcinoma, she started using pazopanib at a dose of 800 mg daily. After one month of use, he started to experience dyspnea on minor exertion, orthopnea and lower limb edema. She was hospitalized for evaluation and management of the condition, her NT-Pro-BNP was 4,500, the electrocardiogram had left bundle branch block and the echocardiogram showed an ejection fraction of 35% with an area of septal and inferior akinesia and hypokinesia of the other walls. In view of this finding, pazopanib was discontinued and the use of enalapril, carvedilol, spironolactone and furosemide was started. An investigation of the etiology of ventricular dysfunction was carried out with the following findings: negative serology for Chagas disease, cardiac catheterization showed no obstructive lesions, cardiac magnetic resonance imaging with no edema, late enhancement or perfusion defects at rest and stress. Therefore, pazopanib was considered the cause of her heart failure. After discontinuation of chemotherapy and initiation of treatment for heart failure, the patient showed clinical improvement and a new echocardiogram showed an ejection fraction of 45%. In a decision shared between the oncology and cardiology teams and with the patient, it was decided to keep the medications for ventricular dysfunction and pazopanib at a lower dose, 400 mg once a day. Conclusion: Pazopanib plays a very important role in the survival of patients with renal cell carcinoma, the incidence of ventricular dysfunction is low and it is a diagnosis of exclusion. Management is challenging and requires shared decision-making between oncology and cardiology, respect for patient values and preferences, and frequent clinical surveillance. 110861 Modality: E-Poster Young Researcher - Case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION The Importance of a Close Follow up for Athletes with Congenital Third Degree Block GABRIELA MELCHUNA MADRUGA1, Rodrigo Otavio Bougleux Alo1, Lucas Yuiti Mori1, Camila Mota Guida1, Marco Antonio Smiderle Gelain1 (1) INSTITUTO DANTE PAZZANESE DE CARDIOLOGIA Congenital third degree block (CHB) is a relative rare disorder. The manifestations of CHB can vary according to many aspects, including ventricular rate of the escape rhythm and ventricular function. The main therapeutic decision is the need for and the ideal timing of permanent pacemaker insertion. Patients with adequate ventricular heart rate increasing appropriately during exertion and no symptoms such as syncope or near syncope and a structurally normal heart and cardiac function can usually be followed without intervention, and therefore, they can selectively participate in competitive sports. Although, this is not a permanent recommendation, and these patients should be followed closely. Case Report: 13-year-old asymptomatic male patient, with a previous diagnosis of CHB, who practices competitive soccer, in yearly follow up at the sports cardiology outpatient clinic, who presented a normal echocardiography, without structural alterations, normal Left Ventricle (LV) dimensions, a Left Ventricle End Diastolic Diameter (LVEDD) of 48 mm, and preserved LV function. His exercise test showed an excellent functional capacity (15 METS) despite a chronotropic insufficiency. However, on the 2021 clinical evaluation, he presented a significant worsening of the tests results, although remained asymptomatic. The new echocardiography presented LV dilatation with a LVEDD of 63 mm, but with preserved ejection fraction. The exercise test showed a worse functional capacity of 11 METS and chronotropic deficit. Therefore, it was indicated the insertion of a pacemaker. New tests were performed two months after the procedure. The echocardiography showed normal LV dimensions (LVEDD: 46 mm). At the cardiopulmonary exercise test, the patient reached 103% of the predicted VO2, showing a normal functional capacity. Although all these improvements, the practice of soccer was contraindicated due to the high risk of thoracic trauma. Nevertheless, the patient still may participate of other competitive and high intensity activities with low risk of lead dislocation and thoracic trauma. In conclusion, the CHB is not a prohibitive condition of high intensity sports, as long as the patient remains without structural cardiac alterations, normal LV function, asymptomatic and with a normal functional capacity. However, these conditions can change in a relative short period, so the follow up must be done closely. 110891 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Libman-Sacks Endocarditis Associated with Mitral Regurgitation in a SLE Patient: A Case Report FLAVIA CORREA DE OLIVEIRA LIMA1, Marilia Spolador Marrafao1, Camila Clara da Costa Geraldo1, Maria Beatriz Marcussi Moretti1, Rafael Cecilio de Lima1 (1) Hospital Regional de Presidente Prudente - HRPP Introduction: Libman-Sacks endocarditis (LSE) - thrombotic, non-bacterial, marantic or verrucous - is characterized by inflammation of the endocardium and sterile vegetations in the heart valves. It is present in 6 to 11% of patients with Systemic Lupus Erythematosus (SLE), with a significant correlation of duration and severity. The development possibly occurs by endothelial injury of circulating cytokines in a patient in a hypercoagulable state, which results in the deposition of platelet thrombi and inflammatory molecules in the valves. Case description: Female, 18 years old, was hospitalized with dyspnea, weakness and bruising for 30 days. Personal history of active SLE with grade III lupus nephritis, hypertension, severe depressive disorder and drug addiction. Patient evolved with persistent high fever, neutropenia, thrombocytopenia, blood pressure peaks and significant worsening of renal function; referred to the intensive care unit. Physical examination: diffuse edema; cardiac auscultation without murmurs and pulmonary auscultation with crackling rales in bilateral bases. Acute intubation with heart failure due to advanced hemodialysis pulse patient edema. Four blood cultures were performed within 30 days, all negative. At the entrance performed Transesophageal Echocardiography (TEECHO), inlet ventricular hypertrophy, mitral function, va a to bicuspid with thickening of the inferior important and echogenic image adhered, filamentous, with random movements, suggestive of endocardial selection. Due to severe thrombocytopenia, it was decided not to perform anticoagulation; clinical support and multidisciplinary follow-up. After 30 exams that showed increased ventricular hypertrophy, increased repetition of myopia, insufficiency and absence of vegetations. In medical records, 9 years ago, ET ECHO with important mitral indication found and leaflet in anterior leaflet with later normalization. At the clinic, a cardiac surgery equipment opted for the conservative approach. Conclusions: Cardiac complications are the ones that most attribute morbidity and mortality to SLE cases. The treatment of the underlying disease with an interdisciplinary approach that included prevention, health education (therapeutic adherence and health care), individualized treatments and diagnosis of complications, such as LSE, can lead to an early risk of negative cardiovascular problems and a better in patient survival. 110960 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Spontaneous Coronary Artery Dissection with Systemic Lupus Erythematosus NOURHAN CHAABAN1, Shilpa Kshatriya2 (1) University of Kansas; (2) Heartland Cardiology Spontaneous coronary artery dissection (SCAD) has been reported to be a rare cause of acute coronary syndrome (ACS) and sudden cardiac death (SCD). We report a case here to emphasize on the benefit of early recognition of SCAD, and to highlight on its association with systemic lupus disease. A 37-year-old female patient known to have hypertension, systemic lupus erythematosus, a history of pre-eclampsia with 3 C-section deliveries, and an active smoking habit presented to the emergency department with chest pain. On arrival, the patient was hypertensive to 152/122 mmHg, with a normal heart rate and respiratory rate. An electrocardiogram (EKG) showed minimum ST elevation in lead V2. Initial troponin was 0.1 ng/mL (normal <0.4 ng/mL) with a peak of 54.5 ng/mL after 6 hours. Aspirin 325 mg was given, and the patient underwent an urgent cardiac catheterization. Intravascular ultrasound was performed that showed evidence of intimal flap (mid LAD) spontaneous dissection with subintimal hematoma. The angioplasty resulted in successful stent placement in the mid-left anterior descending artery. SCAD diagnosis is challenging and requires a high index of suspicion. We aim to elaborate on the association of SCAD with systemic lupus disease and add to the literature this unusual case. 110999 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Purulent Pericarditis Associated with Coronary Thrombosis Due to Escherichia Coli: Hemorrhoidal Disease as the Infection's Origin? POLIANA FERREIRA STROLIGO DIAS1, Paula Bline Lazzari1, Bruno de Souza Paolino1 (1) Hospital Universitario Pedro Ernesto (HUPE) Introduction: Purulent pericarditis is a pericardium located infection characterized by pus. The most common pathophysiology is through continuity or hematogenous dissemination of another infection. It's usually associated with pneumonia and other infection sites are rare. Although the disease is manifested by chest pain, differential diagnosis with acute coronary syndrome (ACS) is made to exclude one of the conditions, since the concomitant presence of pericarditis and ACS is even rarer. Case: 52-year-old smoker and alcoholic male with hypertension and hemorrhoids seeks Emergency Care (EC) with typical chest pain, is diagnosed with inferior STEMI and treated by thrombolysis. He reported anal pain with purulent discharge 15 days before and fever 2 days before but did not use antibiotics. Patient transferred to our institution, still febrile, for invasive stratification after 4 days of EC hospitalization. Coronary angiography showed thrombotic occlusion of posterior ventricular branch (PV), with no atherosclerosis in other vessels. PV angioplasty and thrombus aspiration performed without flow return. Evolution to hemodynamic instability, orotracheal intubation and cardiopulmonary arrest with pulseless electrical activity for 6 min, reversed after CPR. TTE showed pericardial effusion with cardiac tamponade signs, with purulent fluid's output of 300 mL in pericardiocentesis. He was referred to the surgical center, where pericardial window evidenced smooth pericardium. There whas leukocytosis with deviation up to metamyelocyte and CRP elevation in admission exams. Pericardial fluid analysis showed 68600 leukocytes/ml, numerous polymorphonuclear and gram-negative bacilli. Ventilatory and hemodynamic supports were kept and empirical antibiotic therapy with Vancomycin and Meropenem was initiated. The condition worsened, with fever despite antibiotics and antipyretics, progressing to death after 3 days. Later, culture results showed multi-sensitive E. Coli growth in all blood and pericardial fluid samples. Discussion: Purulent pericarditis is a rare and severe disease with mortality up to 30% even with pericardial drainage and adequate antibiotic treatment. Possibly, the infectious condition triggered concomitant coronary thrombosis, another rare but plausible association. Rapid recognition and appropriate treatment are essential for better outcomes and to prevent constrictive pericarditis. 111188 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Case Report: Male Patient, Adult, 31 Years Old, with Single Ventricle, Membranous IVC and Severe Pulmonary Hypertension LARISSA SEBOLD1, Abiran Dalri Merizio1, Barbara Dalri Andreghetoni1, Tiago Goncalves Pereira1, James Alberton1 (1) Cardiological department - Santa Isabel Hospital Introduction: As a congenital heart disease, the univentricular heart may be related to other pathological conditions, such as: pulmonary artery stenosis and aortic obstruction. Within this complex group, the left ventricle hypoplasia (HLHS) is the most common disorder, occurring when there is an underdevelopment of the left ventricle, mitral valve, aortic valve and aortic arch. Typically, it presents in the first 24 to 48 hours of life, due to the constriction of the ductus arteriosus. Adult patients not submitted to repairs usually develop pulmonary stenosis or pulmonary vascular disease. Case Description: AS, 31 years old, male, with congenital heart disease: Single ventricle of left morphology, membranous interventricular communication (IVC), ventriculoarterial connection type "Transposition of the Great Arteries" (TGA) - with pulmonary artery connected to SV, and aorta connected to the hypoplastic chamber - and presence of patent foramen ovale, maintaining signs and symptoms of Heart Failure, with Transthoracic Echocardiogram demonstrating complex cyanotic congenital heart disease (single ventricle + IVC + TGA + Patent Foramen Ovale). Mitral Insufficiency and mild to moderate Tricuspid. Mild Aortic and Pulmonary Insufficiency. Late postoperative of Pulmonary Artery Banding, apparently effective. Moderate enlargement of both Atria. SV with significant enlargement and dysfunction (Ejection fraction:27%). Medication optimization was done and A.S. was listed for performing Heart Transplantation. Conclusion: According to the case above, the clinical manifestations of SV depend on associated cardiac anomalies: if obstructed pulmonary flow, Tetralogy of Fallot clinic, with important cyanosis and without HF; if unobstructed flow, clinical of transposition of great vessels with intraventricular communication, with minimal cyanosis and important HF. When non-operated, many patients succumb to HF from birth, however, the rapid evolution of successful palliation, with surgical approach in stages, has led to a population of adults with only one ventricle. 111026 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Coronary Thrombosis as a Cause of Chest Pain in a Young Anabolic Users: Case Report ANA LUIZA SILVEIRA BORELA PELLIZZER1, Reno Leite Zamignan1, Kamilla Guimaraes Dias1, Pedro Leonel de Paiva Neto1, Ana Paula Lindoso Lima Barreiro1 (1) Santa Casa de Misericordia de Goiania Background: Coronary thrombosis is a serious cause of chest pain and needs to be promptly diagnosed and treated in time, as it leads the patient to the risk of death. One of the causes of coronary thrombosis is the indiscriminate use of anabolic steroids, in most documented reports is the combination of various anabolic steroids. Stanozolol is an anabolic considered the safest among the others, with little probability of complications, for oral use, and which is even approved by the FDA and has grown widely in its use. There are no reports in the literature with the isolated use of Stanozolol associated with serious cardiovascular complications. Case Report: Patient, 25 years old, previously healthy, evolving with tight chest pain, irradiating to the left lower limb, during physical activity (bodybuilding), in which he sought medical attention, and an electrocardiographic diagnosis of acute myocardial infarction with ST-segment elevation on the anterior wall was made. He reports that he had been on regular use of Stanozolol 10 mg once a day for 1 month, denying the use of any other associated medication, such as testosterone, oxandrolone and/or GH. He underwent cardiac catheterization that showed an occluded anterior descending artery with proximal thrombus. Angioplasty and recanalization with intracoronary thrombus aspiration were performed. Due to the presence of residual thrombi and TIMI-II flow, Agrastrat was started. Control catheterization was performed after 5 days in which no intracoronary thrombi were observed, and was then discharged from hospital with outpatient return. Discussion and Conclusion: Stanozolol, the only medication used by the aforementioned patient, is widely used by nutrologists and endocrinologists due to its good efficacy in gaining lean mass and the low probability of complications. The complications documented in publications and articles are neurological changes and hepatotoxicity. This case is of paramount importance, since there are no reports of serious coronary complications in the presence of the use of Stanozolol yet, which should serve as a warning to the general population and health professionals for its use. 112359 Modality: E-Poster Young Researcher - Case Report Category: DYSLIPIDEMIA Impact of C681X Mutation on Treatment of Homozygous Familial Hypercholesterolemia: Review and Case Report GIOVANNA BOLINI BRAZAO1, Isabella Rocha Goncalves1, Eduarda Gabriel Mafra1, Samuel Sabba Fadul1, Ana Augusta Motta Oliveira Valente1 (1) Centro Universitario do Estado do Para (CESUPA) Introduction: Familial hypercholesterolemia (FH) is a genetic disease resulting from the mutation of one of the critical genes for the formation or catabolism of Low-Density Lipoprotein (LDL). Transmission is autosomal dominant and can be heterozygous or homozygous. In about 80% of patients with a definitive diagnosis, mutation can be observed in one of 3 genes: LDL receptor gene (LDLR), gain-of-function mutation in the Protein Convertase Subtilisin/Cexin Type 9 gene (PCSK9) and mutation in the apolipoprotein B (Apo B) gene. Homozygotes will invariably need multiple drugs to control cholesterol, and receptor negative patients will not respond to drugs that act directly or indirectly on LDL receptors. Case details: A 15-year-old man with a diagnosis of homozygous familial hypercholesterolemia by C681X mutation in LDL receptor, as known as Lebanese mutation, one of the most prevalent in Brazil. He has a family history of hypercholesterolemia (father, mother and siblings) and grandmother and uncles who died after AMI under 50 years. On physical examination, corneal arches with cholesterol deposits and tuberous xanthomas on knees, elbows and heels were observed. The treatment was conducted with two distinct pharmacological combined therapy: Therapy 1: rosuvastatin 40 mg daily, ezetimibe 10 mg daily and mipomersen 200 mg every two weeks, for one year. Therapy 2: rosuvastatin 40 mg daily, ezetimibe 10 mg daily and evolocumab 140 mg every two weeks, for one year. The result suggests that the second therapy is better suited to reach the target of 50% reduction in LDL, even without plasmapheresis and in low doses. This corroborates with recent findings that defines C681X mutation as null-receptor mutation, where PCSK9 inhibitors have low efficacy. Conclusion: Studies should be carried out to accumulate data on the distribution of the C681X mutation throughout the Brazilian territory, to pressure public health agencies to create treatment protocols aimed at the Lebanese mutation. 111041 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocarditis After Vaccine for COVID-19 MARIA CLARA SILVEIRA MARQUES PEREIRA1, Thaisa Paula Perini1, Mayara Aparecida da Silva Oliveira1, Juliana Tasso Candido de Lima1, Lucas Simoes de Mello1 (1) Hospital Universitario de Londrina - HU Londrina/UEL Introduction: The coronavirus disease-2019 (COVID-19) pandemic has quickly become a global health problem with high rates of mortality and morbidity. The improvement of the world scenario was possible after the development and wide application of vaccines. A possible complication after vaccination is myocarditis. We report a case of myocarditis after inactivated SARS CoV-2 virus antigen vaccine. Case Report: An 18-year-old male patient attended the emergency department complaining of self-limited episodes of retrosternal chest pain, unrelated to exertion or rest, without irradiation, without other associated symptoms, and lasting up to 1 hour. He denied fever, dyspnea, flu-like symptoms, syncope or other complaints. Personal history of obesity grade III. He received a vaccine for Covid-19 15 days before the onset of the condition. An electrocardiogram was performed on admission, showing sinus tachycardia, positive ultrasensitive troponin result (1.887 - reference value <50 ng/L), NT-pro-BNP 100 (reference value <450 pg/ml). Investigation with chest angiotomography without evidence of pulmonary embolism, chest tomography without alterations. During evolution, the patient showed improvement in chest pain episodes, but with a significant ultrasensitive troponin curve (reaching 3.459 ng/L), without dynamic changes on the electrocardiogram. Considering the hypothesis of post-vaccine myocarditis, cardiac resonance was performed, showing an ejection fraction of 62.9%; area of hypersignal in the inferoseptal wall of the apical segment of the left ventricle (edema); preserved biventricular function; normal-sized cardiac chambers; absence of signs of ischemia at rest or areas of fibrosis . Patient presented spontaneous improvement of pain, being discharged from hospital after investigation. Conclusion: Myocarditis after vaccination is a possible reaction, but with a very low incidence, being more reported among young males, with a good prognosis and a mild and self-limiting course. Therefore the benefits of vaccination outweigh the morbidity and mortality rates associated with COVID-19 infection. 111079 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Sitosterolemia, Advanced Heart Failure, and Mechanical Circulatory Support Implant: A Case Report KAREN KATCHVARTANIAN1, Luis Henrique Silveira Moreira1, Armindo Jreige Junior1, Renan Cintra de Alvarenga Oliveira1, Camila Vilela Vieira1 (1) Instituto do coracao - INCOR-SP L.P., age 46, female, with a previous history of benign familial thrombocytopenia, entry into the InCor emergency room in 2017, receiving a primary diagnosis of acute myocardial infarction with ST segment elevation. Being submitted to an investigation of primary dyslipidemia, sitosterolemia was identified, a rare genetic condition in which lipid metabolism is altered. During hospitalization, the patient developed critical segmental dysfunction and left ventricular failure, with drug therapy being optimized for HF conditions and regular patient follow-up with a specialized team. During hospitalization, progressive worsening conditions evolved presenting multiple organic dysfunctions despite the inotropic drug administration. Chosen MCS (HeartMate 2) as destination therapy, since the patient presented heart transplantation contraindication, because of the elevated immunologic panel due to multiple transfusions by benign familial thrombocytopenia. Sitosterolemia is characterized by hyperabsorption and lowered biliary excretion of dietary sterols, including the phytosterol beta-sitosterol, by plant ingestion. Healthy individuals absorb only about 5% of dietary phytosterols, but sitosterolemia-affected individuals absorb around 15% to 60%. Thus, there is a higher atherosclerosis risk in these patients, and the diagnosis delay has limiting consequences, amongst them, acute myocardial infarction and the subsequent progression to advanced HF when early diagnosis is not achieved. Advanced HF is characterized by heart dysfunction associated with severe symptoms such as dyspnea and fatigue at rest or with minimal physical effort (NYHA III or IV), of life, even with optimized drug therapy, in which life expectancy might be less than two years. At this stage, advanced therapies are considered, including heart transplantation, continuous inotropic therapy, MCS, or palliative care. In 2020, around 3 thousand patients were treated with MCS, and, more than 3 thousand patients had heart transplantation done in the United States, with additional 3,5 thousand patients awaiting transplantation. The importance of support devices as a destination therapy for left ventricularfailure grows incessantly due to organ donor scarcity. However, despite its dissemination, MCS implants still represent a high-risk, burdensome procedure, related to serious adverse events such as right HF, stroke, infection, pump thrombosis, and hemolysis. 111083 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Sitosterolemia, Advanced Heart Failure, and Left Ventricular Assist Device Implant: A Case Report KAREN KATCHVARTANIAN1, Camila Vilela Vieira1, Luis Henrique Silveira Moreira1, Renan Cintra de Alvarenga Oliveira1, Armindo Jreige Junior1 (1) Instituto do coracao - INCOR-SP Heart failure (HF) showed an exponential increase in the last years, affecting about 1-2% of the world'sadult population, and having a significant impact on morbidity and mortality of patients. At the advanced stages of the disease after optimized drug therapy, both a heart transplant and left ventricular assist device (LVAD) implant must be considered for treatment. L.P., age 46, female, with a previous history of benign familial thrombocytopenia, was treated in the Instituto do Coracao de Sao Paulo (InCor) emergency room in 2017, with a diagnosis of acute myocardial infarction, with left ventricular dysfunction development during hospitalization. Was discharged from hospitalization with optimized drug therapy with the outpatient return. At the followup was submitted to an investigation of primary dyslipidemia and sitosterolemia was identified, a rare genetic condition in which lipid metabolism is altered. In 2021 returned to the emergency room due to HF decompensation. During hospitalization, progressive worsening conditions evolved presenting multiple organic dysfunctions despite the inotropic drug administration. Chosen LVAD (HeartMate 2) implantation as destination therapy, since the patient presented heart transplantation contraindication, because of the elevated immunologic panel due to multiple platelet transfusions received. Sitosterolemia is a genetic, autosomal recessive condition, with identified loss-of-function variants in ABCG5 and ABCG8 genes, leading to absorption increase and reduction in the biliary excretion of phytosterol and cholesterol, resulting in prominently elevated serum concentrations. Thus, these patients present tendinous or tuberous xanthomas and early atherosclerosis, similar to familial hypercholesterolemia. The association between the clinical condition of serum sitosterol increase to levels above 1 mg/dl, and pathogenic variant confirmation in the associated genes listed above confirms the diagnosis. The treatment consists of sterol ingestion reduction, so these patients must avoid ingestion of sterol-rich plants such as corn, sesame seeds and oil, peanut, soy, margarine, avocado, and chocolate, associated with standard drug therapy such as ezetimibe and bile acid sequestrants. Sitosterolemia is a rare disease, being of paramount importance its identification to avoid early atherosclerosis. Diagnosis delay has limiting consequences, amongst them, acute myocardial infarction and subsequent progression to advanced HF. 111095 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Acute Coronary Syndrome (ACS) in a Young Woman - Spontaneous Coronary Dissection: A Challenge for the Heart Team SERGIO LAELIO PEREIRA DA SILVA JUNIOR1, Bruno Goncalves Garcia1, Mariana Mancilha Carvalho dos Santos1, Carlos Henrique Oliveira Frango da Silva1, Sergio Laelio Pereira da Silva Junior1 (1) National Institute of Cardiology - NIC Introduction: Spontaneous coronary artery dissection (SCAD) has a low incidence - it represents 0.1 to 4% of ACS cases. However, the cases are underdiagnosed, especially in the early stages of presentation. The evolution of this entity is unpredictable. Keywords: Abstract: A 42-year-old woman with low cardiovascular risk, hospitalized after typical chest pain, with an initial diagnosis of acute myocardial infarction with ST-segment elevation, not thrombolysed, Killip I. Transferred to tertiary hospital for invasive anatomical stratification two weeks after initial event. She presented contractile alteration in the anterior and anteroseptal walls, with global systolic dysfunction of the left ventricle. Invasive anatomical evaluation showed SCAD, involving the left main coronary artery (LMCA) up to the middle third of the anterior descending artery, with TIMI 2 flow. Due to the technical difficulty of percutaneous resolution, clinical and hemodynamic stability of the patient, conservative treatment was initially chosen. After the reappearance of angina at rest, during hospitalization, the Heart Team indicated coronary artery bypass graft surgery, considering the feasibility of the surgical technique of vascular graft anastomosis. The postoperative course was satisfactory, without complications. Conclusions: The diagnostic difficulty of SCAD is a big challenge for Heart Team. The clinical presentation of ACS and/or cardiac arrest in a young patient with low cardiovascular risk strengthens the hypothesis. The diagnosis is mostly angiographic. It includes differentiating iatrogenic and secondary entities to coronary atherosclerosis. The classic angiographic feature - the radiolucid intimal flap is present in less than 30% of non-atherosclerotic cases, which underdiagnoses the condition. The prognosis is a reflection of the degree of involvement of SCAD and according to the modality of proposed therapeutic intervention. Estimates are drawn from retrospective series evaluating outcomes of heart failure, 10-year death, infarction, or dissection recurrence. Cases treated conservatively or with revascularization surgery had better outcomes when compared to percutaneous treatment. 111126 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Giant Coronary Aneurysm Associated with Kawasaki Disease MARIANA FERNANDES GUIMARAES1, Carolina Resende Mariz1, Joaquim Marcio Duarte e Silva1, Viviane Campos Barbosa de Sena1, Aline Reis Bereta1 (1) Instituto Nacional de Cardiologia (INC) Introduction: Kawasaki disease (KD) is an acute vasculitis of unknown etiology that affects medium-caliber arteries. Coronary artery aneurysm is the most feared complication. Case Description: F.N.C, female, 10 years old, diagnosed with KD at nine months. Received immunoglobulin on the 24th day after the onset of symptoms and did not use acetylsalicylic acid. Four years after diagnosis, she evolved with a giant coronary aneurysm. Intake echocardiogram with normal cavitary dimensions and contractility, dilated left coronary artery (LC), greater aneurysm diameter of 0.7 cm. Angiotomography of the coronary arteries with aneurysm (0.63 x 0.55 cm) of the anterior descending (AD). Ectasia in circumflex (Cx) ostium. Giant aneurysm in right coronary (RC) (2.3 x 2.0 cm) with thrombus and subocclusion. Initially, opted for clinical follow-up, since the patient was asymptomatic and scintigraphy did not show stress-induced myocardial ischemia. After five years, the patient developed atypical chest pain and a new scintigraphy suggestive of stress-induced ischemia was performed in the anterior segments of the left ventricle. Coronary angiography presented mild to moderate lesion in the trunk and aneurysm in the LC. Bifurcation of AD with Diagonal Artery presenting significant stenosis. Ectasia in Cx. Occluded RC, with recanalization of the posterior ventricular branch from the collateral branch of Cx. The team indicated myocardial revascularization surgery. Patient awaiting procedure. Conclusion: KD with coronary artery aneurysm is a cause of acute myocardial infarction in early adulthood. It is currently expected that more than 10,000 patients with cardiovascular sequelae have reached adulthood. The understanding of pediatricians and clinicians about this pathology is fundamental. 111155 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cardiac Lipomatosis is not so Benign Disease: A Case Report KAROLYNE MOURA RIQUE DE OLIVEIRA1, Fabio Augusto de Luca1, Ernaque Viana Malta1, Italo Bruno dos Santos Sousa1, Julia Galvani Nobre Ferraz1 (1) Hospital Sao Luiz - Rede D'or Introduction: Cardiac tumors are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, pericardium or the surrounding of the heart, and can be primary or metastatic. The incidence of cardiac tumors is observed to be 0.02%, based on 22 large autopsy data from a United Kingdom center. Almost 75% of all primary tumors of the heart are benign and include myxoma, papillary fibroelastoma, rhabdomyoma, fibroma, lipoma and hemangioma. The lipomas of the heart are encapsulated tumors that are composed primarily of mature fat cells and can originate either from subendocardium, subpericardium or myocardium. Clinical manifestations depend on tumor size and location. The main method for demonstrating lipomatous tumors consist in computed tomography (CT) and magnetic resonance imaging (MRI). Case Report: 42-year-old obese woman with dyspnea on exertion for 8 months, in addition to lower limb edema, orthopnea, and paroxysmal nocturnal dyspnea. A transthoracic echocardiogram detected a mediastinal mass with extrinsic compression of the right atrium and interatrial septum of approximately 72 x 54 mm. Subsequently confirmed by cardiac CT and MRI, suggesting cardiac lipomatosis. On examinations, cardiac chambers had preserved dimensions and biventricular systolic function, without areas of infarction or myocardial fibrosis. The patient underwent thoracotomy for resection of the mass, however, in the intraoperative period, it was visualized multiple tumors with a lipomatous appearance, infiltration in the wall of the right atrium and ventricle, right coronary artery, pulmonary artery trunk extending to the left atrium wall, unresectable. Histopathological examination confirmed cardiac lipomatosis. Thus, the patient had a benign but unresectable primary cardiac tumor with an indication for heart transplantation as the only possibility of a cure. Conclusion: Cardiac lipomas are observed rarely and mostly consist of benign tumors, frequently remaining asymptomatic during a patient's lifetime, but our patient had heart failure-like symptoms. Surgical excision is the treat and has good long-term success and low morbidity. Unfortunately, our patient has an unresectable masses, requiring heart transplantation. It is imperative that cardiac tumors are treated early without making a benign-malignant distinction. In this case, although benign, the lipomatosis was not subject to resection due to the involvement of multiple vital structures. 111157 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Coronary Anomaly by Coronary Angiotomography: A Study Case not Described in the Literature ANNA XIMENES ALVIM1, Maicon Kirchmaier2, Weliton Mendes Apolinario5, Marcos Emanuel Rodrigues2, Thais Ortega Teixeira Guerra6 (1) Hospital Sao Jose do Avai; (2) Universidade Iguacu Campus V - Itaperuna (UNIG); (3) Faculdade Metropolitana Sao Carlos (FAMESC); (4) Cursos de Urgencias Emergencias (CUREM); (5) Universidade Federal Fluminense (UFF); (6) Faminas Introduction: The estimated prevalence of coronary anomalies in the general population is 1.3%, however it is variable and has been described in the literature between 0.21% and 5.8%. In most cases, these are isolated findings, without clinical or hemodynamic repercussions. However, they may be associated with other heart defects, such as valvular heart disease and congenital heart diseases, which may be the cause of myocardial ischemia and sudden death, including sudden cardiac death in young athletes, so their diagnosis and early treatment are important. Case Report: In normal coronary anatomy, the right coronary artery arises from the right coronary sinus (RCS), and the left main coronary arises from the left coronary sinus. It crosses the pulmonary main posteriorly, bifurcating into anterior descending and circumflex. There are reports in the literature of several coronary anomalies, among them, anomalous origin of the circumflex or anterior descending arteries from the RCS. However, there is no description in the literature of cases in which both coronary arteries (right coronary, circumflex and anterior descending arteries) leave the RCS in separate ostia. M.A.O, 61 years old, female, referred by the cardiologist for coronary angiotomography due to atypical chest pain. Physical examination without major changes. The exam performed did not show obstructive plaques, but a coronary anomaly not yet described in literature was found. All coronary arteries emerging from the RCS and with separate ostia. The course of the coronary arteries did not show any characteristics of malignancy, but the RCS was dilated in comparison to the non-coronary and left coronary sinuses. The patient is being followed up by a cardiologist who was alerted to the anomaly found. Conclusion: Angiotomography of the coronary arteries has been essential in the propedeutic of patients with low to moderate cardiovascular risk to detection and exclusion of atherosclerotic plaque. In addition, it presents other highly relevant information, such as the evaluation of coronary anomalies, as described in the case above. 111169 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Fungal Endocarditis: What is the Best Time for Surgery? The Role of a Heart Team CAMILA DALCOMUNI DOS SANTOS1, Igor Henrique Silva Leite1, Rafael Vieira Fernandes1, Airton Salviano de Sousa Junior1, Barbara Porto Valente1 (1) Instituto Dante Pazzanese de Cardiologia - IDPC Fungal endocarditis is an uncommon affliction with high mortality rate; it represents 2% of infectious endocarditis cases with a mortality rate of about 50% and many times diagnosed post-mortem.12 It most frequently affects an adult's aortic or mitral valves. Standardized treatment requires antifungal therapy associated with surgical treatment.3 If there is an uncontrolled fungal infection, an early valvular replacement is recommended (<7 days). Patients that have received only medical treatment have a 100% mortality rate.2 78-year-old male, diabetic, with a previous bioprosthetic aortic valve replacement due to severe aortic stenosis, attended the emergency department with fever for the past two months, initially once a week and recently twice daily, associated with nonspecific unwellness and chills. He brought transthoracic echocardiogram that suggested prosthetic valve endocarditis. The patient was hospitalized. Blood cultures were taken and a transesophageal echocardiogram done, which showed typical vegetation annexed to the prosthetic's aortic ring (7 x 7 mm) with mobile component projecting out of the left ventricle and restricting the opening of the prosthetic valve in this region, causing an increase of its gradients. A multi-sensitive Candida parapsilosis was shown in the blood cultures and then Anidulafungin 200 mg/day was initiated for an estimated 42-day treatment. The case was discussed with Heart Team because of the high surgical risk and the early need of valve replacement. Initial course of action had us schedule surgery for the seventh day of the antifungal treatment. Patient maintained daily fever and blood cultures were collected every 72h showing increase in Candida parapsilosis in all samples and surgery was sped up. The patient was submitted to a bioprosthetic aortic valve replacement with amplification of the ring due to the presence of abscess evidenced in mid-surgery. The patient was admitted in critical condition to the ICU, hemodynamically unstable in use of ascending vasoactive drugs, in vasoplegic shock with refractory septic component. The patient remained refractory to instituted measures evolving to death 24h after surgery. Fungal endocarditis is a rare but extremely serious condition, and a multidisciplinary approach is extremely important. Discussing a case of reoperation with high surgical risk with all those responsible for the care is the role of Heart Team and was essential to decide the best time for the surgery. 111174 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Case Report: An Unexpected Case of Minoca in a 56-Year-Old Male with Myocardial Bridge CAMILA DALCOMUNI DOS SANTOS1, Rafael Vieira Fernandes1, Airton Salviano de Sousa Junior1, Igor Henrique Silva Leite1, Barbara Porto Valente1 (1) Instituto Dante Pazzanese de Cardiologia - IDPC Introduction: A myocardial bridge (MB) is typically asymptomatic, but sometimes can lead to a myocardial infarction with several mechanisms such as: coronary spasm, thrombosis, coronary dissection, or the development of focal atherosclerosis immediately proximal to the MB. Sometimes more than one mechanism can be present. The use of intracoronary images modalities, as Optical Coherence Tomography (OCT) in patient with MB can accurately define the mechanism of the myocardial infarction and provide further guidance to management strategy. Case Report: 56-year-old male with past medical history of systemic arterial hypertension and active tobacco use, attended the emergency department with severe oppressive chest pain after a long car trip in the heat. The initial electrocardiogram showed ST-elevation in anterior leads. Coronary angiography revealed a myocardial bridge with a systolic constriction of more than 90% in the proximal third of the left anterior descending artery (LAD), OCT demonstrate a lesion <20% with no signs of rupture. The patient was diagnosed with MINOCA with multiple mechanisms such as supply and demand imbalance, cigarette-induced vasospasm and hypovolemia. The patient was treated with beta blockers and antiplatelet therapy and discharged 3 days later. There was no recurrence of chest pain at follow-up appointments. Conclusion: Myocardial bridge (MB) is a congenital anatomic anomaly whereby a length of the artery tunnels beneath a section of myocardium. It can potentially be associated with phasic arterial spasm and ischemia. About 67-98% of cases have their anatomical location in the LAD. The gold standard for diagnosis is autopsy, but angiography and OCT provides more information about MBs, such as assessment of vulnerable plaque and coronary morphology. Unlike classic atherosclerotic plaque that produces a fixed stenosis, MB produces a dynamic effect that varies with cardiac cycle, heart rate, and sympathetic tone. According to the classification by Schwarz 2009, this case is classified as type C, with altered intracoronary hemodynamics. The clinical management was maintained with pharmacological therapy, which is the mainstay treatment. Angioplasty would be suggested only for cases with refractory symptoms. The patient was conducted with medications for management of heart failure and general orientation, with no recurrence of chest pain. 111198 Modality: E-Poster Young Researcher - Case Report Category: ANTICOAGULATION Thrombolysis in Metallic Prosthetic Valves: A Series of Cases in a Tertiary University Hospital NATANAEL MENDES DE ARAUJO1, Natanael Mendes de Araujo1, Ana Paula Otaviano1, Andre Schmidt1 (1) HOSPITAL DAS CLINICAS DA FACULDADE DE MEDICINA DE RIBEIRAO PRETO DA UNIVERSIDADE DE SAO PAULO Background: Prosthetic valve thrombosis (PVT) is an important and severe complication of valvar replacement. Until today, treatment guidelines are scarce. Methods: A consecutive series admitted to a tertiary university hospital is reported. All of them were presented in a Heart Team meeting and surgical intervention was denied by various reasons. Non-fractioned heparin was started and patients reevaluated five days later with Doppler echocardiography to identify signs of improvement. Patients with sustained leaflet impairment and/or significant transvalvar gradient, an ultra-slow thrombolytic infusion protocol (Alteplase 25 mg in 25hours) followed by non-fractioned heparin was started and after completion a new echocardiographic evaluation was performed. A descriptive analysis is presented. Results: Six patients (4 females), 53 +- 9 years with a diagnosis of PVT admitted in two consecutive years were evaluated. Three (50%) of them had a metallic prosthesis in the mitral position, two (33%) in the aortic and one (17%) in the tricuspid position. All of them were using warfarin but the INR values were infra therapeutic (1.12 to 1.88). Two of the patients with mitral prosthesis had a significant reduction of transvalvar gradient (51% mean reduction) and good leaflet mobility and did not received thrombolytic. In the other 4 patients, thrombolysis was started and after completion of the protocol a mean gradient reduction of 69% was observed. Only the patient with a prosthesis in the tricuspid position had thrombolytic protocol repeated due to incomplete recover of leaflet mobility. No hemorrhagic or embolic complications occurred. All patients were discharged alive. Conclusion: Thrombolytic treatment using an ultra-slow infusion protocol was safe and presented a high effectiveness, suggesting that large studies are needed to define its indications. 111200 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Interventricular Septum Rupture After Acute Myocardial Infarction: Late Diagnosis and Favorable Outcome LETICIA MACACCHERO MOREIRAO1, Leonardo Giglio Goncalves de Souza1, Gisele Messias Mattioli1, Alex dos Santos Felix1, Matheus Burigo Oliveira1 (1) Instituto Nacional de Cardiologia (INC) Introduction: Rupture of the interventricular septum (IVS) is a surgical medical emergency and it is part of mechanical complications of Acute Myocardial Infarction (AMI), which can occur between 2 and 14 days after the event. Like the other ones, it becomes increasingly rare in the "post reperfusion" era. An incidence of 0.2% is estimated in the US, mainly when associated with single-vessel transmural infarction or the first event. Even with surgical treatment, it is still followed by high rates of mortality, reaching 80% in the first 30 days if not corrected. Clinical Case: R.S.M., 62 years old, male, white. Carrier of Diabetes Mellitus and dyslipidemia, he reports a sudden episode in October/2020 of chest pain. Diagnosed with AMI at the time, not reperfused. In the following two weeks, the pacient developed dyspnea on exertion, orthopnea associated with worsening of functional class (NYHA II). On physical examination, he presented a holosystolic murmur in the lower left parasternal border. A transthoracic echocardiogram was performed, with diagnosis of ventricular septal defect measuring 1.8 cm associated with multiple communicating orifices, LV > RV shunt showing a gradient of 85 mmHg. Coronary angiography showed severe subtotal lesion in the right coronary artery. The patient was hospitalized after a year and a half of the acute event for evaluation of surgical treatment, maintaining the symptoms described. After discussion with Heart Team, we opted to correct communication with bovine patch. Conclusion: Rupture of the IVS is a rare mechanical complication of AMI, with high mortality rates if not corrected early. The illustrated case presents a patient with a late diagnosis of this complication, a large area of communication and a favorable outcome even without initial surgical correction, which is rare according to the literature. BIBLIOGRAPHY: ABDULA, A.D. et al. Mechanical Complications of Acute Myocardial Infarction: A Scientific Statement From the American Heart Association. American Heart Association. Jul/21. THIELE H., ABBOTT J.D. Acute myocardial infarction: Mechanical complications. UpToDate, 2022. 111205 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Aortic Dissection in Childhood: A Case Report and Literature Review LEONARDO PAIVA OHASHI1, Luiz Augusto de Andrade Costa1, Jose Cicero Stocco Guilhen1, Jose Honorio de Almeida Palma da Fonseca1, Celia Maria Camelo Silva1 (1) Escola Paulista de Medicina/Universidade Federal de Sao Paulo Aortic dissection is a serious disease with a high mortality, characterized by the delamination of the media and intima layers of the vascular wall, promoting a rupture in the endothelium of this vessel. Despite of being studied in the adult population, it is rare in the pediatric population and there are few findings in the literature, which makes the management of these cases quite challenging. In this case report, a patient 9 years and 9 months old, male, 28 kg, student, was admitted on 24 of april 2021 to the emergency department of a tertiary hospital with a complaint of abdominal pain within the last 3 hours. He was accompanied by his mother, who revealed that the patient woke up with severe abdominal pain in the upper abdomen region (9 on a scale of 10). The pain radiated to the back and substernal region, and was accompanied by nausea and three episodes of vomiting. He denied similar previous events and any change in bowel habits, as well as fever or urinary symptoms. At birth, he was diagnosed with polycystic kidney disease and evolved with the need for a kidney transplant performed at the of four. There was no family history of aortic disease or a family history of sudden death. On admission physical examination, the physical examination was innocent, except for a absent peripheal pulse on the left upper limb. The admission tests showed mild leukocytosis with no deviations, with other laboratory tests within the normal range. Acute abdome routine X-rays were performed that only showed the presence of mediastinal widening. Aortic CT was then performed (figure 01), with the presence of a dissection flap that extended from the aortic arch to the bifurcation of the common iliac arteries. After a hypertensive peak, the patient evolved for a cardiorespiratory arrest anda despite all efforts during the CPR the death was confirmed at 00:00. This pathology can occur at this age group in 22% of cases, but, classically is relates to congenital anomalies, mainly those of the connective tissue. This way, early diagnosis and treatment are essential for better clinical outcomes. 111213 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Konno-Rastan Procedure for Correction of Aortic Prosthesis Mismatch and Left Ventricular Outflow Tract Stenosis LUIS HENRIQUE COELHO PINTO1, Gabriela Zamunaro Lopes Ruiz1, Claudio Leo Gelape1, Luiz Guilherme Passaglia1, Maria Leticia Leao Lana1 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais - HC-UFMG Introduction: Konno-Rastan procedure is an anterior aortoventriculoplasty originally described for the correction of congenital aortic stenosis, whether subvalvular, valvular or supravalvular. We report a case of an adult patient evolving with a major mismatch of a mechanical aortic prosthesis after 5 invasive surgical procedures due to congenital stenosis of the aortic valve and left ventricular outflow tract (LVOT). Case Description: Female patient, 37 years old, with congenital aortic valve disease associated with LVOT stenosis, who underwent 5 other surgical procedures - aortic commissurotomy in 1996 and 1999, valve replacement for a biological prosthesis in 2009, valve replacement for a mechanical prosthesis in 2013 (No. 19 - Standard), exploration of the valve with 3 linear incisions in the fibrosis of the interventricular septum (subvalvular) - evolving with NYHA functional class III dyspnea, chest pain, palpitations and presyncope on exertion. Transthoracic echocardiogram (TTE) showed a 40 mm left atrium, 25 mm aorta, left ventricle with mild hypertrophy, normal cavity and preserved ejection fraction. Mechanical aortic prosthesis with thickened discs, preserved opening and mobility. Maximum gradient of 87 and mean of 52 mmHg, valve area of 0.9 cm2. The patient underwent cardiac surgery in January 2022, using the Konno-Rastan technique, in which a section of the valve annulus, enlargement of the annulus and LVOT with section of the interventricular septum and septal myectomy were performed, followed by reconstruction of the annulus and septum with bovine pericardium patch and St. Jude model Regent No. 21 mechanical aortic prosthesis implantation. There were 134 minutes of cardiopulmonary bypass and 116 minutes of aortic clamping. The patient evolved in the postoperative period with severe vasoplegia and complete atrioventricular block. Bichamber pacemaker implantation was performed 8 days after surgery. Postoperative TTE showed a reduction in the mean transprosthetic gradient to 10 mmHg. She was discharged from hospital 16 days after surgery. The patient remains under follow-up, asymptomatic, maintaining echocardiographic parameters within normal limits. Conclusion: The Konno-Rastan procedure is a complex tecnique that proved to be an adequate option for the correction of the LVOT stenosis and mismatch presented by this patient, since it involved valvular, subvalvular and supravalvular stenosis not corrected in previous approaches. 111221 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Spontaneous Coronary and Carotid Arteries Dissection Associated with Cerebral Aneurysm in a Young Woman ISABELLE MENDES RODRIGUES SALOMAO1, Alessandra Arnez Pacheco1, Daniel Xavier de Brito Setta1, Julia Paulo Mourilhe Rocha1, Ricardo Mourilhe-Rocha1 (1) Hospital Pro-Cardiaco Introduction: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of myocardial infarction (AMI), reaching approximately 1% of cases and may be associated and may be rarely associated with carotid dissection. In most cases, it is underdiagnosed and may evolve to worse prognosis and even sudden death. Case report: Female, 36 years old, white, with a history of arterial hypertension, gestational diabetes and overweight. She reported stabbing chest pain, 10+/10, for 40 minutes, at rest, without irradiation, associated with sudden dyspnea, nausea and sweating. Normal electrocardiogram (ECG) and positive troponin I (TnI). Reported improvement in her symptoms after aspirin and clopidogrel and was transferred to another hospital asymptomatic. A new ECG was performed, which showed T wave inversion in the anterior and inferior walls and TnI us = 3,950 ng/mL. Echocardiogram (ECO) with severe left ventricular (LV) systolic dysfunction, hypokinesia of the basal segments and akinesia of the middle and apical portions of the LV. Coronary angiography (CAT) was performed, which showed spontaneous anterior descending dissection (ADA), 1st. diagonal, septal and 1st. marginal with TIMI III flow. One day after the CAT, she evolved into a new chest pain with hemodynamic stability and ECG with a new ST elevation in the inferolateral wall, being maintained with ASA, clopidogrel, statin and associated with bisoprolol. Cardiac resonance was performed, which showed recent transmural AMI affecting the anteroseptal wall of the LV (7% infarcted mass) and subendocardial AMI in the inferolateral wall (3% infarcted mass). Coronary CT angiography with absence of atherosclerosis with images of dissections in the middle third of the ADA and moderate dissections in the distal third of the right coronary artery. Angiotomography of the neck and skull showed saccular aneurysmal dilatation in the ophthalmic segment of the right internal carotid artery (ICA) measuring 6 mm and dissection in the distal cervical segment of the left ICA. After clinical control, she was discharged from the hospital in NYHA functional class 1 with improvement in LV function by ECO. Conclusion: SCAD is more prevalent in young women with few risk factors for coronary artery disease and may be related to fibromuscular dysplasia, pregnancy and the puerperium. The association with vascular alterations in other sites must be resherched in those patients. Conservative treatment had been chosen in most cases. 111223 Modality: E-Poster Young Researcher - Case Report Category: NURSING Valve-in-Valve Tavi: First Case of Balloon-Expandable Prosthesis in Self-Expanding Prosthesis Performed at a University Hospital in Southern Brazil EMILY JUSTINIANO1, Rejane Reich1, Juliana Kruger1, Dulce Daise Guimaraes1, Paola Severo Romero1 (1) Hospital de Clinicas de Porto Alegre Introduction: Aortic stenosis is the most prevalent acquired valvular heart disease in the Brazilian population and has high morbidity and mortality. Transcatheter aortic valve implantation (TAVI) is an established procedure for the treatment of symptomatic stenosis for patients considered inoperable, at high risk and intermediate surgical risk. Objective: To report the first case of balloon-expandable prosthesis implantation in a degenerated self-expanding prosthesis performed in a public university hospital in southern Brazil. Case description: An 86-year-old female patient with a history of TAVI CoreValve prosthesis in 2012 was hospitalized with an echocardiogram showing aortic prosthesis with severe stenosis and moderate insufficiency, and a new TAVI (valve in valve) was chosen. The catheterization laboratory team previously performed combinations with the operating room team due to the possibility of conversion to a surgical approach. In addition to alignments with regard to materials, a team of professionals developed strategies to deal with intercurrences. The procedure was performed in September 2021, under general anesthesia, with transesophageal echocardiography follow-up. A balloon-expanded prosthesis, Sapien 3 23 mm, was implanted inside a previous prosthesis, by puncture in the right femoral artery (7 and 14 French introducer) and left femoral artery (7 French introducer). Passed 6 French introducer in the right femoral vein for transvenous pacemaker and in the right radial artery for catheterization of the right coronary artery. Hemostasis was performed with a suture closure device (Perclose) in the right femoral artery and by compression in the other access sites. Patient transferred to intensive care unit extubated and without vasopressor. The procedure time was 215 minutes and the room time was 337 minutes. Four medical specialties participated in the procedure, a nurse, two nursing technicians, a radiology technician, a prosthetic representative, in addition to a perfusionist and an instrumentation specialist in cardiac surgery present at the unit. The patient evolved satisfactorily and was discharged from the hospital on the tenth day after the procedure. Conclusions: The nurses of the catheterization laboratory, together with a team of professionals, actively participated in the organization of material resources and the logistics outlined for the care of a possible surgical approach. The procedure, although complex, was uneventful. 111234 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Quadricuspid Aortic Valve in a Patient with Mucopolysaccharidosis Type 1: A Case Report DANIEL FIORAVANTI GIMENEZ1, Elaine dos Reis Coutinho1, Eduardo Hadad Cherulli1, Marina Romano Capellini1, Aloisio Marchi Rocha1 (1) Hospital da Introduction: The Mucopolysaccharidosis is a group of rare autosomal recessive metabolic disorders which affects multiple systems, including cardiovascular. It's characterized by deficiency of lysosomal enzymes (alpha-L-iduronidase) that leads to accumulation of glycosaminoglycans in tissues and in consequence, tissue dysfunction. Mucopolysaccharidosis type 1 (MPS1) has an estimated prevalence of 1:100.000 births. This case reports a patient with MPS1, Scheie phenotype, with severe aortic stenosis. Case Report: A 47-year-old woman with MPS1 diagnosis since birth and with preserved ejection fraction heart failure (echocardiogram 03/21: left ventricular ejection fraction (LVEF): 51%) was admitted at emergency room with low cardiac output accompanied by pulmonary congestion due to COVID and Bacterial Pneumonia. The echocardiogram revealed: LVEF:25%, globally reduced, absence of segmental disorders, left chambers enlargement with Left Ventricular hypertrophy, malformed aortic valve (quadricuspid aspect) with mild thickening and calcification, critical stenosis and subtle insufficiency. Also, there was an severe mitral insufficiency with ring dilatation, apical systolic closure and posterior leaflet prolapse. The cardiac surgery team was opposed to an aortic valve replacement procedure due to high surgery risk. TAVI was not possible due to an unfavorable anatomy for the procedure and iodine allergy. Regarding her decreased mobility and NYHA functional class I, she was discharged and keeps her follow up in the ambulatory with optimized clinical therapy. In less severe MPS phenotypes, there may be valvular disorders independent of existing risk factors as congenital or rheumatic atherosclerosis. Therefore, the cardiological follow up is important for those patients, as pointed out in the case, in which an adult patient presents severe aortic stenosis with ventricular function loss secondary to MPS 1. Conclusion: The cardiovascular disease emerges subtly in attenuated phenotypic presentations of MPS, contributing to the premature mortality of these patients. Besides being rare, MPS 1 may present late cardiovascular implications, even in broader cases, and severe consequences that compromise the patient's lifestyle. The case is even more uncommon not only for its underlying disease, MPS 1, but for the aortic valve's anatomic modification (quadricuspid), not often reported in literature in this syndrome. 111233 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES The Role of Non-Invasive Intracranial Pressure Monitoring in Hemodynamic Management of Critical Care Patients AMANDA AYAKO MINEMURA ORDINOLA1, Salomon Soriano Ordinola Rojas1, Caroline Spagnol1, Viviane Cordeiro Veiga1 (1) Beneficencia Portuguesa de Sao Paulo Intracranial pressure (ICP) assessment is a method that can guide the hemodynamic management of patients undergoing procedures and conditions associated with neurological disturbances. In this paper, two cases were reported. The first case is a 40-year-old male with Marfan's syndrome, admitted with aortic endocarditis which underwent valved conduit exchange with extracorporeal circulation (ECC) 182 minutes, the patient presented one episode of tonic-clonic seizure. Non-invasive ICP (NIICP) showed altered brain compliance (figure 1). The management included increase in sedation and prevention of secondary cerebral ischemia. New NIICP showed well response to the neuroprotection management (figure 2). The second is a 64-year-old female diabetic patient admitted for cytoreductive surgery due to colon adenocarcinoma. Edema and facial plethora were presented on admission, associated with high central venous pressure and high systolic volume variation. The hypothesis of superior vena cava syndrome was raised and confirmed by evidence of thrombosis related to catheter. The NIICP showed altered brain compliance (figure 3), with improvement after cerebral protection measures. In all cases reported, NIICP identified morphological changes in the ICP waveform and throughout patient management in the intensive care unit. Noninvasive method assisted in clinical decision-making regarding the optimization of protocols adapted for neuroprotection. 111236 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Aortic-Right Atrium Fistula and Pulmonary Tromboembolism After COVID-19 Infection: Case-Report YURI CAVALCANTI ALBUQUERQUE TENORIO1, Priscila Alves da Silva2, Stephanny Isabelly Pessoa Neri de Araujo2, Igor Vieira Lima Alexandre2, Francisco de Assis Costa2 (1) Hospital Veredas; (2) Centro Universitario Tiradentes Introduction: Several cardiac complications have been described after the beginning of pandemic Covid-19, such as myocardial ischemia, acute cardiac heart failure, arrhythmia and myocarditis. Case description: M.J.F.S., female, 43 years old, denied any chronic disease or use of medication, admitted to the ward of a high complexity hospital presenting cardiac heart failure (NYHA IV) and oedema in the lower limbs. The patient had Covid-19 infection two months before and presented a normal routine transthoracic echocardiography (TT-ECHO). After the admission, a new TT-ECO presented global dilatation of cardiac chambers, specially left atrium (LA) and signs of coronary sinus of valsalva rupture and Aortic-Right Atrium (Ao-RA) fistula. These findings were confirmed in a transesophageal echocardiography, that presented left ventricle ejection fraction of 69%, rupture of sinus of valsalva aneurysm at aortic root promoting strong shunt from aorta to right atrium and cardiac chambers dilatation. Thoracic angiotomography described bigger dimensions of the right atrium and signs of pulmonary thromboembolism. Therapeutic decision included surgical correction of Ao-RA fistula, which occurred with complication of complete heart block requiring transitory pacemaker and cardiac arrest successfully reverted to systemic circulation. Definitive cardiac pacemaker was implanted and the patient was discharged in a stable clinical situation after 59 days of hospital stay. Conclusion: The clinical report presents rupture of sinus of valsalva aneurysm leading to Ao-RA fistula and pulmonary thromboembolism two months after Covid-19 infection. As a consequence, the authors suggest linkage between Covid-19 and thrombogenic state and inflammatory process leading to endomyocardial inflammation. 111245 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Thrombolysis in Biological Mitral Valve on a Patient with High Surgical Risk ARIANE ZONHO WOGEL1, Andrei Carvalho Sposito1, Marcelo Sousa1, Renata Muller Couto1, Silverio Fernandes1 (1) Universidade Estadual de Campinas (UNICAMP) Introduction: Prosthetic valve thrombosis is a rare and highly lethal complication, more frequently found in mechanical valves and in the mitral position. The treatment involves systemic anticoagulation and valve replacement surgery. Thrombolysis appears as a second option, due to its complication rates and low efficacy. Case Report: A 65-year-old man who underwent mitral bioprosthesis implantation for severe secondary mitral regurgitation returns after 3 months with dyspnea and, on transthoracic echocardiography (TTE), prosthesis dysfunction due to thrombosis (Image 1: A-C). There was also a global dilation and left ventricular systolic dysfunction (ejection fraction of 17%). Due to a prohibitive surgical risk (EUROSCORE 34%), alteplase 25 mg was administered for 6 hours followed by full anticoagulation with intravenous unfractionated heparin. TTE 24 hours post thrombolysis showed thrombus reduction, improvement in valve motion, and a drop in the transvalvular gradient (Image 1: D-E). The same dose of alteplase was repeated after 48 hours, resulting in improvement in dyspnea, and in valve opening and mobility on TTE (Image 1:F-G). There was no bleeding or adverse effect and he was discharged with Warfarin. Conclusion: Fibrinolytic therapy for prosthetic biological valve thrombosis remains controversial due to the lack of evidence of its benefit and safety. Hence, its use has been sporadic and restricted to critically ill patients who are at high surgical risk. The case presented here stands out for the efficacy and safety of fibrinolysis in severe thrombosis in a mitral bioprosthesis. This report deserves consideration as a therapeutic possibility either in clinical research or in similarly unfavorable clinical conditions. 111265 Modality: E-Poster Young Researcher - Case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Mechanical Ventricular Assistance Devices: A Case Report PALOMA DE BORBA SCHNEIDERS1, Heloise Benvenutti1, Ane Glauce Freitas Margarites1, Mauren Porto Haeffner1, Fernanda Cecilia dos Santos de Vasconcellos1 (1) Hospital de Clinicas de Porto Alegre Introduction: Heart Failure is the final pathway for heart diseases. Considering limiting situations such as lack of donors and contraindications to the Heart Transplant (HTx) new strategies are needed. Mechanical Ventricular Assistance Devices allow patients to be able to perform physical exercises in Cardiac Rehabilitation. Description of Cases: Case 1: FPB, male, 54 years old, ischemic etiology. Ejection Fraction 32%, HTx contraindicated due to immunological hypersensitivity. After HeartMate II, had reduced respiratory muscle strength - RMS (PiMax: 18/PeMax: 37) and cardiorespiratory fitness - CRF (distance in six meters walking test: 261 m). Preserved peripheral muscle strength - PMS (28 KgF) and no self-care limitations (SCL). Case 2: JSP, female, 50 years old, chagasic etiology. Ejection Fraction 16%, HTx contraindicated due to immunological hypersensitivity. After HeartMate II, had reduced RMS (PiMax: 34/PeMax: 46) and CRF (383 m). Preserved PMS (18 KgF). After hospital discharge showed improvement in CRF (429 m). Case 3: MHPD, female, 61 years old, Dilated Cardiomyopathy etiology, worsened after chemotherapy. Ejection Fraction 13%, HTx contraindicated due to pulmonary hypertension. After HeartMate III, had reductions in RMS (PiMax: 50/PeMax: 56), PMS (17 KgF), CRF (273 m) and SCL (Katz: 2). Case 4: LBF, female, 63 years old, Dilated Cardiomyopathy etiology. Ejection Fraction 16%, HTx contraindicated due to pulmonary hypertension. After HeartMate II, had SCL (Katz: 2) and present reductions in RMS (PiMax:75/PeMax:109), PMS (28 KgF) and CRF (390 m). Case 5: AAAV, male, 61 years old. Dilated and non-ischemic etiology. Ejection Fraction 20%. After HeartMate II, had some complications (driveline infection, massive pleural effusion, multifactorial anemia) and prolonged stay (154 days). At hospital discharge, he could walk more than 30 m, but failed to perform the walking test; SCL (Katz: 3); adequate PMS (25 kgF). Conclusion: Hospital Cardiac Rehabilitation was performed with aerobic, respiratory/peripheral strength and balance training. All patients had reductions in RMS and PMS. Two of them had functional SCL and two of them had low exercise tolerance (<300 m). These patients' CRF may be reduced, due to low adaptive capacity to increase cardiac output during physical exercise. Potentially reversible extracardiac factors such as muscle atrophy and deconditioning seem to improve patients' functionality. 111274 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Coronary Ectasia as a Cause of Acute Myocardial Infarction ISMAR JUNIOR PEINADO LIJERON1, Larissa Kaline Santana Diniz1, Marina Albanez Albuquerque de Medeiros1, Soraia Rachid Youssef de Campos1, Valeria Mozetic de Barros1 (1) Instituto Dante Pazzanese de Cardiologia IDPC Introduction: Aneurysmal dilatation of the coronary arteries is found in up to 5% of the patients undergoing coronary angiography, with higher incidence in men and proximal segments of the coronary artery. The right coronary artery (RCA) is more affected (40%), followed by the left Anterior Descending (AD) (32%). Atherosclerosis, vasculitis, genetic susceptibility and post infection are reported as possible etiologies. The presence of coronary aneurysm or ectasia has been associated with a worse long-term prognosis. Case Description: Female, 48 years old, with no previous diseases, presented with an unprecedented typical chest pain after performing moderate physical exertion. On the electrocardiogram it was observed sinus rhythm with electrically inactive area in the inferior wall and positive troponin. Performed coronary angiography that showed important ectasia of RCA, AD with mild ectasia in the proximal third and other arteries with discrete parietal irregularities. Echocardiogram shows akinesia of the inferolateral wall and of the middle and basal segments of the inferior wall and ejection fraction 58%. The angiotomography of coronary arteries confirmed ectasia of RCA, measuring in its largest diameters 10.8 x 10.4 mm and thrombosis in the distal third. Started anticoagulation with warfarin and clopidogrel together with antianginal drugs and after treatment she got angina improvement and had no new thromboembolic events. Conclusion: Aneurysmal dilatation of the coronary vessels is an unusual. Antiplatelets and anticoagulation are the most addressed therapy, but there are possibilities of performing percutaneous coronary intervention or surgical resection. The treatment is still controversial, requiring more randomized studies to define the best and safest treatment strategy. 111515 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Importance of Genetic Testing and Early Diagnosis of Cardiac Amyloidosis: A Case Report ANTONIO FELICIANO FATORELLI1, Vitor Agueda Salles1, Elisangela Cordeiro Reis1, Leticia Macacchero Moreirao1, Jacqueline Sampaio dos Santos Miranda1 (1) Instituto Nacional de Cardiologia Introduction: Cardiac amyloidosis (CA) is a systemic disease caused by tissue deposition of fibrillar and insoluble protein aggregates in different organs, including the heart, leading to organic dysfunction. Different subtypes of amyloidosis can give rise to overlapping clinical manifestations. The importance of carrying out the genetic test is due to the need to correctly characterize the precursor protein for the institution of specific treatment. Thus, the present report aims to describe the case of two patients diagnosed with transthyretin-linked (TTR) AC and discuss the importance of genetic testing, as well as early diagnosis for a better prognosis. Case Report: These are two elderly patients, 71 and 83 years old, with a clinical picture of advanced heart failure, who had indicators in the anamnesis, physical examination and complementary exams of CA and whose etiology was confirmed during the workup. Both had immunoglobulin heavy and light chain form (AL) ruled out with investigation for monoclonal light chains by means of serum and urinary immunofixation, in addition to measurement of the serum kappa/lambda ratio. On pyrophosphate scintigraphy, grade III uptake was identified, one of them with extensive involvement of the right ventricle, corroborating an advanced stage of the disease. Despite the high prevalence of wild type ATTR CA in the elderly population, both were tested for mutation of the ATTR V122l gene. This mutation is well established as a pathogenic variant, with heterozygosity being the most common. It presents after the age of 60 with predominantly cardiological involvement, with a higher frequency in Afro-descendants, which possibly makes it frequent in our country. Specific therapy was instituted with selective stabilizers of TTR tetramers with good tolerance and the patients are in follow up. Conclusion: Thus, CA could be considered an underdiagnosed condition, rather than a rare disease. The patient's journey to diagnosis is long; it is estimated that there is a delay of more than 2 years from symptom onset to diagnosis, with the involvement of an average of five different professionals. Thus, it is essential to disseminate knowledge about CA; clinicians and cardiologists must give greater consideration to this entity, aiming at earlier diagnosis and adequate therapeutic guidance, thus improving patient prognosis and survival. 111931 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Video-Assisted Pericardial Window as an Alternative in Patient with Thoracic Deformity: A Case Report LEONARDO PAIVA OHASHI 1, Diego Felipe Gaia dos Santos1, Paulo Matheus Sanches de Souza1, Aislan Henrique Bezerra Pinheiro1, Pedro Reges Pereira Meira1 (1) Escola Paulista de Medicina/Universidade Federal de Sao Paulo Pericardial effusion is a common finding in clinical practice with a spectrum manifestations ranging from asymptomatic mild effusions to cardiac tamponade. As a minimally invasive form of treatment, video-assisted pericardial window is an alternative intervention. A patient, 73 years old, male, referred to a tertiary hospital for investigation of Asthenia, dyspnea, chronic low back pain, loss of 10 kg in 3 months and solid expansive lesion in the pre-sacral region. The patient had a history of hypertension, Kyphoscoliosis, Pectus Carinatum, Alcoholism for 15 years and previous treatment of gastric ulcer. Laboratory and imaging findings at admission and during hospitalization culminated in a diagnosis of Multiple Myeloma. During the institution of chemotherapy, an echocardiographic follow-up was performed, which showed growth of the pericardial effusion lamina, which progressed from asymptomatic to the presence of signs of ventricular restriction and symptoms of cardiac tamponade. As a result, it was decided to perform a pericardial window before hospital discharge. However, the presence of previously described thoracolumbar deformities, added to the massive abdominal hernia caused by diastasis of the rectus abdominis, precluded the classic subxiphoid surgical approach or through lateral thoracotomy. It was then decided that the only therapeutic possibility would be the use of videothoracoscopy (figure 1). In perioperative care, multiparametric monitoring, invasive blood pressure acquisition through the right radial artery puncture, central venous access in the right Femoral Vein, and Orotracheal Intubation were performed. Intraoperatively, 400 ml of serohematic fluid was released, with a drain in the chest on the right. After the procedure, the patient improved with dyspnea, maintaining chest drainage for 5 days. This is a patient diagnosed with Multiple Myeloma who evolved during hospitalization with significant pericardial effusion and signs and symptoms of cardiac tamponade. Due to the chest deformity that made conventional drainage unfeasible, a video-assisted intervention was chosen. 111330 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Extracorporeal Membrane Oxygenation as a Bridge to Transplantation: A Successful Case Report RAIANE FONSECA SILVA HERDY1, Douglas Fernandes de Souza1, Nathalia Targa Silva1, Alina de Souza dos Santos1, Marcia Barbosa de Freitas1 (1) Instituto Nacional de Cardiologia Introduction: Mechanical circulatory support has been increasingly used in refractory cardiogenic shock associated with conventional treatment in patients with severe heart failure (HF). The literature indicates use as a bridge to recovery for transplantation (Tx) for decision or target therapy. We report the case of using venous-arterial extracorporeal membrane oxygenation (ECMO) in a young patient with cardiac Tx indicated already in use intra-aortic balloon (IAB) and maintenance of low cardiac output that recovered his clinical condition and subjected to Tx. Case Description: A 38-year-old male patient with dilated cardiomyopathy for 2 years developed severe heart failure in NYHA III-IV despite optimized medical therapy. He was indicated cardiac Tx due to disease progression. The patient was hospitalized several times due to HF decompensation in a cold and wet hemodynamic profile, requiring high-dose inotropic support. In the current hospitalization, even with inotropic, his case deteriorated, with several parameters of poor tissue perfusion (lactate increase, renal function worsening, increased transaminases and bilirubins). Already with association of 2 inotropic (Dobutamine and Milinone), as well as vasopressor (norepinephrine and vasopressin), was indicated a device of short permanence circulatory support, IAB. The next day there was maintenance of critical state, which led to an indication of ECMO. There was a significant improvement of oliguria, significant decrease in lactate and plasma creatinine. Two days later, a compatible organ emerged, the patient underwent Tx, extubated six days after the procedure and recovers well from necrotizing pneumonia acquired during hospitalization. Conclusions: ECMO is indicated as a bridge to another device or to Tx in severe heart failure when the patient has refractory cardiogenic shock. Therefore, patients with non-recoverable cardiac function should not be selected. The success of the therapy involves a multidisciplinary team trained with experience in this technology. In the case presented, the use of ECMO associated with systematized care was fundamental to keep the patient viable until the emergence of a compatible organ. Thus, heart transplantation was possible and the patient recovered from the baseline clinical condition, illustrating a good example of the successful use of ECMO as a bridge to cardiac Tx. 111332 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Infective Endocarditis of the Right Heart: Second Case Report in the Literature of Tricuspid Involvement by Staphylococcus Caprae FELIPE KESSLER PEREIRA1, Luanna Damasceno Amaral de Sousa1, Julia Paulo Mourilhe Rocha1, Daniel Xavier de Brito Setta1, Ricardo Mourilhe-Rocha1 (1) Hospital Pro Cardiaco Introduction: Infective endocarditis of the right side (IELD) of the heart is an entity where there is microbial involvement of the tricuspid or pulmonary valves and is responsible for 10% of all cases of infective endocarditis (IE). Case Report: M.B.B, 59 years old, male, with arterial hypertension, dyslipidemia, type I diabetes mellitus, hypothyroidism, coronary artery disease, was admitted to the hospital with atypical chest pain associated with chills, fever, and vomiting. Acute coronary syndrome was ruled out and the hypothesis of myopericarditis was raised, and pharmacological treatment with colchicine was initiated. Despite the established treatment, the patient continued to experience chills and vomiting. Blood cultures were collected and antimicrobial therapy with vancomycin was administered empirically. There was growth of vancomycin-sensitive Staphylococcus caprae, but in the investigation of IE with transesophageal echocardiography, there was no evidence of vegetations. A scintigraphy with labeled leukocytes was then performed to screen for an infectious focus and the tricuspid valve was the only point of evidence of an inflammatory process, confirming the diagnosis of IE, subsequently being treated with antibiotic therapy for 6 weeks. Discussion: Staphylococcus caprae is part of the group of coagulase negative staphylococci (CoNS) and was isolated for the first time in goat milk. Later, it was described as a component of the microbiota of healthy human skin, nails, and nasal mucosa, living symbiotically with its host. S. caprae is a rare cause of infective endocarditis, even more so of native valve. In the literature review, we found a single case report, published in 1995 by Vandenesch et al, of infective endocarditis caused by S. caprae. The case was reported in situ mitral valve involvement, which was treated with intravenous antibiotics for 2 weeks and early surgical removal of the vegetation, preserving the valve, with a good clinical outcome. The main predisposing factors for S. caprae infection are recent use of antibiotics, malignancies, diabetes mellitus, chronic renal failure, open fractures, immunodeficiency, and immunosuppression associated with systemic or local corticosteroids, chemotherapy, radiotherapy. Seng et al. observed that 21 of the 25 patients with S. caprae infection were male, supporting the sex preference hypothesis previously made by Shuttleworth et al. 111348 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Coronary Reperfusion Dilemas from Admission to Outpacient Follow-Up THALES CARDOSO WHATELY1, Joao Gabriel Monteiro Junqueira1, Ana Salome Eurico1, Jose Ary Boechat e Salles1, Esmeralci Ferreira1 (1) Hospital Universitario Pedro Ernesto; (2) Universidade do Estado do Rio de Janeiro Introduction: The main etiology of acute ST-segment elevation myocardial infarction (STEMI) is the rupture of atherosclerotic plaque with thrombus formation. However, other less common etiologies, such as vasospasm, COVID 19 and coronary embolism, should be considered and investigated when there are risk factors, being important to define the best treatment for each patient. Case Report: Female, 56 years old, former smoker, with systemic arterial hypertension, ischemic stroke (CVA) for one month with motor sequelae (right hemiparesis) and aphasia. Sought emergency for typical anginal chest pain. An electrocardiogram was performed, which showed atrial fibrillation rhythm and ST-segment elevation from V1 to V6, DI and AVL (extensive anterior wall STEMI). She was not submitted to fibrinolytic therapy due to absolute contraindication for stroke in less than 3 months. She was referred to the hemodynamics department, and occlusion of the anterior descending artery was evidenced with a negative image, suggestive of a thrombus, without severe obstructive lesion. As reperfusion therapy, mechanical thrombus aspiration was performed followed by implantation of a drug-eluting stent, reestablishing the coronary flow. Transesophageal echocardiogram showed severe left ventricular dysfunction with anterior hypokinesia and presence of thrombus in the auricle. Cranial resonance was performed with ischemic images suggestive of thromboembolism. In view of the results of the complementary exams, the most likely hypotheses for acute coronary syndrome are atherosclerosis associated with coronary embolism caused by thrombus in the auricle related to unkown atrial fibrillation. Dual antiplatelet therapy (clopidogrel and ASA) and full anticoagulation were initially started, with outpatient and echocardiographic follow-up to assess cardioversion and adjusts in antiplatelet therapy. Conclusion: The authors describe a patient with STEMI due to high thrombotic load, recent stroke and presence of atrial thrombus, whose treatment dilemmas begin with the impossibility of using fibrinolytic therapy, the decision to perform thrombus aspiration and the definition of the best post-reperfusion pharmacolocgical therapy. 111756 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Coronary Vasospasm as a Cardiovascular Repercussion of Severe Obstructive Sleep Apnea: A Case Report CATHARINA TUROLLA DE ANDRADE 1, Roberta Dutra Fortes1, Luiza Gondim Toledo4, David Nigri3, Erverton Gregorio de Andrade2 (1) Hospital de Forca Aerea do Galeao; (2) Clinica Sao Vicente da Gavea - Rede dOr Sao Luiz; (3) Hospital Copa Star - Rede dOr Sao Luiz; (4) Universidade Federal do Rio de Janeiro - UFRJ Introduction: Obstructive sleep apnea (OSA) is a disorder characterized by obstructive apneas, hypopneas or respiratory effort-related caused by repetitive collapse of the upper airway during sleep. The estimated prevalence is 30 percent in males. It is essential to recognize OSA as a predisposing factor for cardiovascular disorders. This case report aims to show the occurrence of coronary vasospasm (CV) in a patient with OSA. Case Report: A 67-year-old male, body mass index 26, ex-smoker, systemic arterial hypertension, chronic coronary artery disease (three previous stents), with a known high rate of admissions in the emergency room for acute pulmonary edema (APE), has been readmitted at the hospital with similar acute symptoms started during sleep. The vital signs showed desaturation, tachypnea and high blood pressure. Respiratory auscultation with bibasal crackles. The patient has been hospitalized for clinical surveillance and further investigation for APE. Troponin was elevated in one dosage, electrocardiogram showed no acute alterations, transthoracic echocardiogram was normal and a chest computerized tomography with a pattern of congestion. Despite the initial treatment, the patient continued to have episodes of hypoxemia and dyspnea, especially during sleep, and further complementary tests were requested. The patient underwent coronary angiography, which revealed vasospasm in the circumflex artery and marginal branch with a focal lesion of 70 percent, reversing during the exam with intracoronary mononitrate infusion [figure1]. Polysomnography showed severe OSA. The patient received specific treatment - continuous positive airway pressure and oral nitrate - with significant clinical improvement, remained asymptomatic after discharge. Conclusion: This report presented demonstrates CV as a cardiovascular repercussion possibly caused by severe OSA. Recognizing OSA as predisposing factor for cardiovascular dysfunction is essential to provide adequate therapy, prevent complications, reduce symptom exacerbation and morbidity for these patients. 111377 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Whipple's Endicarditis: A Case Report CAROLINA KUCHENBECKER SOARES1, Claudio Leo Gelape1, Robson de Souza Almeida Junior1, Geraldo Brasileiro Filho1, Luiz Guilherme Passaglia1 (1) Hospital das Clinicas da UFMG Introduction: Whipple's disease (WD) is a rare chronic multisystem illness caused by the bacterium Tropheryma whipplei. Most patients have polyarthritis, malabsorption and anemia. Up to 50% can present with cardiac manifestations, being infective endocarditis (IE) with negative blood culture considered the most frequent and aortic valve the most affected. Case description: A 63-year-old woman, previously healthy, is admitted in the Emergence Department with sudden left hemiplegia. Head tomography confirmed stroke showing acute hypodensity in right corona radiata. Carotid doppler was normal and transthoracic echocardiogram showed a filamentous structure in the ventricular face of the right coronary leaflet of the aortic valve, 9.3 mm long, with moderate regurgitation (confirmed by transesophageal exam). There were no clinical or laboratory signs of infection. Serial blood cultures, rheumatoid factor, abdominal ultrasound, and urinalysis were normal. In view of the possible differential diagnosis of IE, fibroelastoma and Lambl excrescences, as well as the concern for further embolization, cardiac surgery and excision of the material was chosen for anatomopathological diagnosis. She was then submitted to aortic valve replacement with a bioprosthetic valve, an uneventful procedure. The slide evaluation showed mononuclear cell infiltrate with foamy macrophages containing PAS-positive granulations, diagnosing WD. Conclusion: Although rare, WD can be prone to recurrences and its recognition is important to initiate target therapy with parenteral streptomycin and benzylpenicillin for 14 days, followed by oral trimethoprim-sulfamethoxazole for 1 year. Unlike common IE, WD occurs mainly in native valves, without underlying disease and the anatomopathological pattern of inflammation is fundamental, as Trophyerma whipplei cannot be cultured using standard techniques. The presence of prodromes such as gastrointestinal symptoms or arthritis should also be considered in the suspicion. 111911 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Case Report: The Efficacy of PET-CT in Prosthetic Valve Endocarditis ERICA SILVA1, Bernardo Santos Resende1, Ingred Hellen de Resende Andrade1, Henrique Patrus Mundim Pena1, Carlos Eduardo Ornelas1 (1) Rede Mater Dei de Saude Introduction: Infective endocarditis (IE) is a high mortality rate (30-50%) disease with many clinical features. Thus, some diagnoses may be challenging. Increase in the use of prosthetic materials and intracardiac devices (ICD) follows the importance of complementary tests, as 20% of EI patients have valve prosthesis or ICD. Duke criteria, traditional in IE diagnosis, are based on the presence of typical microorganisms in hemoculture and suggestive valve alteration in echocardiogram. However, in over 20% of cases, these may be inconclusive, requiring extended propaedeutics with more accurate exams. Thus, in other suspicious cases, more exams are essential for a precise diagnosis, such as Positron emission tomography (PET-CT). Case Report: F.J.S.M., 59 years old, 15 years with an aortic biologic prosthesis, was admitted to ER reporting paresthesia of left upper limb, lips and tongue, of short duration and spontaneous recovery. Neurology assessed the case and nuclear MR of the skull showed cerebral ischemia area suggesting embolic etiology. Cardiological follow-up and complementary propaedeutics were started for etiologic investigation. Transesophageal echocardiogram image suggested aortic biologic valve periprosthetic vegetation. Patient had no symptoms of infection. Serial hemoculture results showed no bacterial growth. So, under Duke criteria, IE diagnosis was inconclusive (1 major, 2 minor criteria). PET-CT with radiopharmaceutical FDG-18F aimed at cardiac assessment confirmed hypothesis showing hypercaptation of the radiopharmaceutical, circumferential, in the aortic position biologic prosthesis, compatible with valve infective endocarditis. Directed treatment initiated with empiric antibiotic therapy and heart surgery for valve replacement. Conclusions: As the use of prosthetic materials and intracardiac devices (ICD) advances, it is necessary to perform exams other than the traditional doppler echocardiography. Such information follows the European IE Treatment Guidelines (ESC 2015), which cites use of PET-CT in patients with clinical suspicion, when the evidence of valve periprosthetic abnormal activity is a major criterion in IE diagnosis. In the case described, PET-CT was essential to confirm IE diagnosis in patient with valve prosthesis, when Duke criteria were inconclusive. It is a high mortality disease, so, when it is suspected, even with atypical signs, investigation must be exhaustive to minimize risk of improper treatment. 111434 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Atrial Septal Defects, Arrhythmias and a Novel Tbx5 Gene Variant ANNE KATHRINE MOLLER NIELSEN1, Lars Allan Larsen2, Vibeke Hjortdal1 (1) Department of cardiothoracicsurgery, Rigshospitalet, Copenhagen, Denmark; (2) Institute of cellular and Molecular Medicinen, University of Copenhagen, Denmark Background and aims: Patients with atrial septal defect (ASD) have increased mortality and morbidity. This can only be partly explained by hemodynamic changes caused by the ASD, suggesting additional underlying causes. Patients with an ASD have an increased burden of pathogenic gene variants in ASD related genes, indicating genetics as an important etiologic factor. This study aimed to investigate genetic associations in familial ASD and comorbidities. Methods: In a cohort with familial ASD we identified a family with ASD present in 12 family members in three generations. We performed whole exome sequencing on five family members older than 18 years to detect the causative gene variant in this family and evaluated phenotype. Results: We identified a novel pathogenic variant within the T-box domain of TBX5 (F232L) in all affected family members over 18 years of age. They presented with diverse cardiac phenotypes including heart failure and arrhythmias. Two carriers needed a pacemaker. Skeletal malformations where subtle with small hands as the only visible malformation. These findings propose Holt-Oram syndrome. Conclusions: We report a novel variant in TBX5 in a family with Holt-Oram Syndrome, characterized by septal defects, severe cardiac arrhythmias, and mild skeletal malformations. Clinical awareness of family history, arrhythmias, and heart failure in patients with familial ASD is important and may lead to timely treatment and uncover patients with Holt-Oram Syndrome. 111478 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Octogenarian with Refractory Heart Failure, Dextrocardia and Multivalvular Disease - A Complex Case Report with a Successful Percutaneous Approach HENRIQUE TROMBINI PINESI1, Vinicius Esteves1, Francisco Monteiro de Almeida Magalhaes1, Rafael Alves Franco1, Carlos Vicente Serrano Junior2 (1) Rede D'OR Sao Luiz; (2) Instituto do Coracao, Faculdade de Medicina, Universidade de Sao Paulo Introduction: The percutaneous approach of valvular diseases has gained increasing importance in recent years, especially in frail, elderly and high surgical risk patients. However, procedures in the tricuspid valve are still rare. Case Description: Female, 87 years old, previously independent for instrumental activities of daily living, with a history of dextrocardia, dual-chamber pacemaker and difficult-to-manage atrial fibrillation requiring atrioventricular node ablation. She presented with progressively worsening dyspnea up to NYHA class III/IV, fatigue, and progressive swelling of the extremities in the last 4 months, with two hospitalizations due to acute heart failure in this period. Transthoracic echocardiogram identified preserved biventricular function, with significant biatrial and right ventricular dilatation. The Mitral valve showed significant regurgitation with prolapse and the tricuspid valve severe regurgitation with failed coaptation and torrential reflux secondary to annular dilation. A transesophageal echocardiogram identified dilatation of the valve annulus with a slight thickening of the cusps in addition to prolapse of segments A1/A2 of the anterior cusp and P1/P2 of the posterior cusp, with significant reflux. After optimization of medical treatment, she remained symptomatic with signs of congestion, associated with worsening of renal function. After discussion with the Heart Team, considering the patient's elevated surgical risk (STS mortality of 17,29%), a less invasive treatment was chosen. A combined procedure was successfully performed, with a percutaneous mitral valve edge to edge repair (MitraClipTM) and heterotopic tricuspid treatment with percutaneous bicaval valve implantation (TricValveTM). The procedure was a success despite the difficulties caused by the simultaneous multivalvular approach in a patient with dextrocardia. The patient evolved with clinical improvement and normalization of ventricular function. She was discharged with a great enhancement in functional capacity. Conclusion: We present a rare and up to the moment, the first description case of an elderly patient with dextrocardia, high surgical risk and refractory heart failure who underwent successful percutaneous treatment of the mitral and tricuspid valves simultaneously. 111481 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Subacute Lactobacillus Endocarditis in Blalock Prosthesis: A Case Report RAPHAELA TEREZA BRIGOLIN GAROFO1, GUILHERME COELHO FORTES1, ISABELLE DE OLIVEIRA PARAHYBA1, CAMILA VIEIRA VILELA1, RAYZA KARLLA SALLES ARAUJO1 (1) HOSPITAL DO CORACAO - ASSOCIACAO DO SANATORIO SIRIO Introduction: The diagnosis of infective endocarditis is often difficult. We found diagnostic limitations especially in patients with prosthetic valves and implantable cardiac electronic devices. Case Report: A 37-years-old man, diagnosed at birth with tricuspid hypoplasia, significant right ventricle hypoplasia and wide atrial septal defect with bidirectional shunt. He has been submitted to Blalock-Thomas-Taussig surgery on the right at 2 years old and on the left at 20 years old. Between 2019 and 2020 he was diagnosed with pneumonia on 4 occasions. After six months he continued to present with weight loss, low fever at night and asthenia, with elevated serum inflammatory markers. In July 2020, he sought the Emergency complaining of ventilatory-dependent chest pain and worsening of asthenia. Chest tomography showed a consolidation area in the right lung and antibiotic therapy was initiated. Even after the end of treatment, the patient remained subfebrile and with elevated C-Reactive Protein. Blood cultures were positive for Lactobacillus casei, paracasei and Rhamnosus. Due to the clinical suspicion of an undetermined infectious focus and with a negative investigation for Infective Endocarditis, an 18FDG PET/CT was performed, which showed an increase in glycolytic metabolism in a focal area next to the vascular prosthesis interposed on the left in the pulmonary systemic anastomosis. The diagnosis of prosthetic valve infective endocarditis was confirmed. After antibiotic therapy guided by blood cultures, the patient showed clinical and laboratory improvement. He was discharged asymptomatic, with a negative blood culture and normalized inflammatory markers. Lactobacillus are commensal microorganisms of humans and are recognized as a rare cause of endocarditis in people with previous comorbidities. When questioned, the patient reported daily ingestion of Lactobacillus-based probiotics. Conclusion: The FDG-18F PET/CT should be used when there is a high clinical suspicion without diagnostic confirmation with traditional methods in a patient with a prosthetic valve or intracardiac device. 111485 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocarditis Associated with Coronary Thrombosis After Vaccine for COVID-19: Case Report RAPHAELA TEREZA BRIGOLIN GAROFO1, GUILHERME COELHO FORTES1, THAIS DOS SANTOS VIEIRA1, LAURO MARTINS NETO1, CAROLINA TOSI PIRES1 (1) HOSPITAL DO CORACAO - ASSOCIACAO DO SANATORIO SIRIO Introduction: Chest pain in young patients without comorbidities is a challenge. This report is relevant since the patient in the case presented with acute myocarditis associated with acute coronary thrombosis. Case Report: A 20-year-old male patient without previous diseases and with a history of myocarditis 4 years ago. He went to the emergency room with type C chest pain for four hours. An electrocardiogram was performed with no changes. Laboratory tests with troponin curve (0.638 and 2.570 - Reference 0.034). Due to the hypothesis of myocarditis, a Cardiac Magnetic Resonance (CMR) was performed, which showed anterior and anterolateral hypokinesia associated with myocardial edema, and non-ischemic late mesoepicardial enhancement in these segments. It was decided to perform coronary CT angiography due to the segmental alteration on CMR, which showed proximal occlusion in the Anterior Descending Coronary Artery (ADCA) and its diagonal branches. Coronary Angiography was performed in association with Optical Coherence Tomography, which showed acute thrombosis in ADCA without signs of atherosclerosis. The thrombus was aspirated and a stent was implanted. After these findings, the patient reported a dose of mRNA vaccine for COVID-19 21 days before admission. The coronavirus causes a condition of hyperinflammation and hypercoagulability, leading to dysfunctions of various organs, including the heart. Among the cardiac dysfunctions we can mention myocarditis and thromboembolic events. Myocarditis should be considered in young people with chest pain after mRNA vaccine. He had an episode of acute myocarditis and ADCA occlusion with high thrombotic burden without evidence of atherosclerosis, other etiologies for myocarditis and rheumatologic disease. Due to its recent vaccination history for COVID-19, it is likely that the vaccine was the protagonist of the activation of the coagulation cascade and the inflammatory response. Conclusion: This case reinforces the importance of differential diagnoses in young patients with atypical chest pain in order to promote adequate treatment. 111500 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Case Report: Amniotic Fluid Embolism in a Public Maternity Hospital in the State of Amazonas RODRIGO BINDA DE MAGALHAES LOIOLA 1, Emerson Oliveira Lise3, Laura Barbosa David4, Gisele Tezolin Menezes5, Alexandre Lobato Rodrigues Guimaraes6 (1) Faculdade Metropolitana de Manaus; (3) Faculdade Metropolitana de Manaus; (4) Faculdade Metropolitana de Manaus; (5) Faculdade Metropolitana de Manaus; (6) Maternidade Estadual Balbina Mestrinho Amniotic fluid embolism (AFE) is a rare and exclusive complication of pregnancy, and is characterized by the sudden onset of maternal impairment. It usually involves the cardiorespiratory and hematological systems, and can progress to cardiac arrest and coagulopathy, leading to death. The estimated incidence of AFE is 1:15,200 and 1:53,800 births in North America and Europe, respectively. The mortality rate associated with AFE is 30%. The objective of this report is to emphasize the need for knowledge of this serious clinical entity. Patient 21 years, G2P2A0C2, GA 38 weeks and 1 day, admitted to the maternity hospital. Ultrasound with Doppler was requested, by which signs of fetal centralization were found, and cesarean section was indicated. On the 1st day post cesarean section (PCS), in the operating room, she suddenly developed acute respiratory distress and cardiorespiratory arrest (CRA), with return of spontaneous circulation after the first cycle. Sent to the ICU, where she presented 2 more CRAs, both with return in the first cycle. On the same day, the patient developed cardiogenic shock, requiring the use of vasoactive drugs for hemodynamic compensation. Wells criteria: with a high probability of PTE. Laboratory tests and echocardiogram (ECG) were requested, which revealed an increase in right chambers, pulmonary artery systolic pressure (PASP) 68 mmHg. On the 2nd day PCS, ECG showed dilatation of the right ventricle (RV) and right atrium (RA), left artery collapse, dilated inferior vena cava, dilated superior vena cava, presence of pulmonary hypertension with PASP: 60 mmHg. On the 3rd day PCS, she suffered 2 more CRAs, with return in the first cycle. On the 4th day PCS, weaning of vasoactive drugs and sedation was initiated, ECG was requested, dilated inferior vena cava not collapsing with inspiration, RV in "D" due to high pressure, PASP: 60 mmHg, RA increased in size. On the 5th day PCS, extubation was performed. On the 6th day, patient was hemodynamically stable without the use of vasoactive drugs, in good general condition. Presented edema of upper limbs+++/4+ and lower limbs ++/4+. Started on furosemide. On the 8th day, she started captopril due to BP of 149/85 mmHg. On the 9th day PCS, the patient was discharged from the ICU. Although rare, AFE should be maintained as a differential diagnosis for intensivists and obstetricians. Their knowledge is of paramount importance for the early recognition and proper management of the patient. 111528 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Heart Failure with Reduced Ejection Fraction After Biontech-Pfizer Vaccine BARBARA MARIANA DOS SANTOS SILVA1, Carlos Eduardo Lucena Montenegro1, Fiamma Ferreira Nogueira1, Raquel Cristina Farias de Medeiros Queiroz1, Claudia Carolina Mendonca Campos1 (1) Pronto Socorro Cardiologico de Pernambuco (PROCAPE) Introduction: Cardiac complications such as post-vaccination myocarditis from BioNTech-Pfizer have been reported. There is prevalent in young men, evolving with fever, chest pain and dyspnea in the first days after the vaccine. Active infection is ruled out by negative RT-PCR and in all cases MRI showed delayed myocardial enhancement after contrast. Most of the reported cases showed complete resolution of symptoms and absence of sequelae after supportive therapy. Cases of myocarditis have a difficult etiological diagnosis, but they should be considered as part of the clinical diagnosis. Case Report: A 42-year-old woman, previously diagnosed with hypertension, dyslipidemia and overweight, with no other comorbidities, presented to the emergency department with progressive dyspnea started about 2 months ago, progressing to dyspnea on minimal exertion, orthopnea and paroxysmal nocturnal dyspnea. On physical examination, the patient presented with signs of pulmonary and systemic congestion and cardiac auscultation without alterations. She reported onset of symptoms after 1 week of taking the BioNTech-Pfizer COVID-19 vaccine, reporting only a few episodes of associated retrosternal chest pain. She had normal laboratory tests, ECG with sinus rhythm and left bundle branch block pattern, chest X-ray that showed signs of pulmonary congestion, transthoracic echocardiogram with left ventricle showing moderate enlargement, walls with diffuse hypokinesia and markedly reduced systolic function (SIMPSON ejection fraction 25%), cardiac catheterization without evidence of atherosclerotic disease and cardiac MRI with late mesocardial enhancement after gadolinium infusion, with signs of non-ischemic fibrosis in the septal-lower segments and inferior basal and middle, suggestive of sequel of previous inflammatory/infectious process. Optimized treatment was started for heart failure with reduced ejection fraction (sacubitril-valsartan, bisoprolol, spironolactone and furosemide), the patient evolved with significant symptomatic improvement. The patient has had no recurrent symptoms since hospital discharge and is currently under the care of the heart failure center. Conclusion: Post-vaccination myocarditis is a rare event, but it should be considered a differential diagnosis after vaccine for COVID-19, especially when it has a temporal relationship with the BioNTech-Pfizer vaccine. Its evolution is still uncertain and clinical follow-up in specialized centers is necessary. 111532 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Research of Thrombus in the Left Ventricle in a Patient After Acute Myocardial Infarction: A Case Report ANDRE DIAS NASSAR NABACK1, Anderson Ferreira Leite1, Lucas Queiroz Fernandes Campos1, Larissa Barroso Mayrink2, Thales Moura De Battisti1 (1) Hospital das Clinicas da Universidade Federal de Minas Gerais, HC-UFMG; (2) Centro Universitario de Belo Horizonte, UniBH Introduction: Left ventricular (LV) thrombus is one of the complications after acute ST-segment elevation myocardial infarction (STEMI), mostly in cases of anterior wall STEMI with LV ejection fraction <50%. For its diagnosis, transthoracic echocardiography (TTE) is the initial method of choice. Clinical case: Male, 76 years old, diagnosed with STEMI of the anterior wall and submitted to primary angioplasty of the left anterior descending coronary artery (LAD) three and a half hours after the onset of symptoms. One day after the procedure, he presented with transient mental confusion and rotational vertigo. Cranial computed tomography showed a dubious image of an ischemic area in the posterior fossa region. ECOTT did not show intracavitary thrombus, despite an LV ejection fraction of 44%. Nine days after the STEMI, he again presented chest pain and V2-V6 ST-segment elevation on the electrocardiogram. Coronary angiography showed proximal thrombosis of drug-eluting stent in LAD requiring balloon angioplasty and tirofiban infusion. One day later, he recurred with chest pain and worsening of the ST-segment elevation, requiring a new balloon angioplasty due to a new stent thrombosis in the LAD. Changed P2Y12 receptor inhibitor. Two new TTE did not show intracavitary thrombus. It was decided to perform magnetic resonance imaging (MRI) of the heart, which confirmed an image compatible with a thrombus adhered to the apex of the LV, measuring 18 x 10 x 4 mm. Brain MRI confirmed cerebellar ischemic area. Then, anticoagulation with warfarin was started. Conclusion: Intracavitary thrombi are commonly underdiagnosed. Although TTE is the most accessible test, its sensitivity is 35%. The use of ultrasound contrast is an alternative to improve the performance of the exam (sensitivity of 64%). However, despite being less accessible and more expensive, MRI is the gold standard for the diagnosis (sensitivity of 82%-88% and specificity close to 100%), being indicated for patients with high probability of LV thrombus and TTE without thrombus. 111938 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Acute Type a Aortic Dissection Secondary to Closed Thoracic Trauma: Two Stage Approach, a Case Report ELISA ITO MENDES DE ANDRADE1, Jose Carone Filho1, Marcio Luiz Roldi1, Jose Carone Junior1, Carlos Alberto Sancio Junior1 (1) Hospital Evangelico de Vila Velha Introduction: Acute type A aortic dissection secondary to trauma is a potentially fatal cardiovascular emergency that needs to be diagnosed early and treated effectively. Redirection of blood flow to the true lumen with prosthetic grafts is the mainstay of treatment. Method: A 58-year-old man was admitted to the hospital in his city after a power pole fell. A CT scan was requested due to a suspected fracture of the facial bones. In addition to confirmed bone lesion, he showed acute type A (Stanford) aortic dissection secondary to trauma. The patient was transferred to the referral service in cardiovascular surgery, where computed tomography angiography (CT Angio) of the thoracic aorta showed "Flap in the aortic arch and emergence of the brachiocephalic trunk, with flow maintained in them. The other segments of the thoracic aorta had normal caliber, walls and flows". He underwent transsternal thoracotomy, and aortic derivation from the proximal aorta to the carotids with a bifurcated graft (Debranching) and implantation of an endoprotheses with antegrade approach without cardiopulmonary bypass (CPB). He is discharged from the Intensive Care Unit (ICU) on the fourth day after surgery, being transferred for surgical treatment of mandibular fracture. Returns to the emergency room 49 days after discharge, complaining of atypical chest pain, which started one week ago, with significant worsening that day. A new CT angiography of the aorta showed the presence of an endoprosthesis that extended from the emergence of the brachycephalic trunk to the descending portion of the thoracic aorta, with contrasted content outside the proximal portion of the endoprosthesis and in apparent continuity with the intimal flap, suggesting an II/IA ? endoleak. He underwent transfemoral implantation of a 36/36/150 endoprosthesis in the ascending aorta and arch, requiring the use of an accommodation balloon with excellent results. The patient progressed satisfactorily in the postoperative period, being discharged on the third day after the approach. Discussion: It is estimated that about 80% of patients with acute type A aortic dissection secondary to trauma die even before hospital care. Endovascular treatment is not the first option for type A aortic dissection, but in this case the patient was at high risk of serious complications if submitted to heparinization and cardiopulmonary bypass. A study with the objective of long-term follow-up of patients undergoing endovascular treatme. 111565 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Atypical Manifestation of Infective Endocarditis BARBARA MARIANA DOS SANTOS SILVA1, Diana Patricia Lamprea Sepulveda1, Raquel Cristina Farias de Medeiros Queiroz1, Suellen Lidia da Silva Barbosa1, Deborah Rodovalho de Menezes1 (1) Pronto Socorro Cardiologico de Pernambuco (PROCAPE) Introduction: Infective endocarditis has different forms of presentation. Signs and symptoms result from either local destructive effects of the cardiac endothelial surface, metastatic embolization of infected fragments, hematogenous seeding of other sites or antibody formation. Typical clinical features are fever, weight loss, malaise, pulmonary or peripheral congestion and new or changing heart murmur. In rare cases, it may be associated with cutaneous vasculitis or hepatitis. Case Report: A 36-year-old man with a rheumatic heart disease, has undergone mitral and aortic valve replacement in 2008 and aortic valve replacement with tricuspid valve repair in 2018, referred progressive dyspnea for about 3 months associated with febrile episodes and jaundice. His initial laboratory panel showed a marked increase in leukocytes with neutrophilia, thrombocytopenia, elevated CRP, liver dysfunction (AST 528/ALP 357) and hyperbilirubinemia (TB 15,1/DB 12,5). Abdominal imaging exams without changes. On examination, the patient was emaciated, with moderate intensity jaundice, diffuse purpuric lesions, signs of peripheral embolization and jugular distension. On cardiac auscultation, important systolic and diastolic murmurs in the mitral focus and systolic murmurs in the aortic and tricuspid areas. Pulmonary auscultation with crackling rales in lung bases. Transesophageal echocardiography revealed moving filamentous images suggestive of vegetation on the atrial face of the mitral bioprosthesis, in addition to signs of mitral, aortic and tricuspid valve dysfunction. Antibiotic treatment with oxacillin, ceftriaxone, gentamicin and rifampicin was started, with gradual improvement in a few days of the purpuric lesions and the icteric syndrome. Initial blood cultures with negative results. The patient underwent a new surgery to replace the aortic and mitral valves (mechanical) and tricuspid repair. During hospitalization, positive control blood culture samples for Candida albicans and Candida haemulonii were evidenced. Antibiogram-guided treatment with micafungin was performed. Patient was discharged clinically stable and with improvement of all initial clinical and laboratory findings. Conclusion: Infective endocarditis can appear in an atypical manner and can be a diagnostic challenge in such cases that initial signs are these rare complications, such as hepatic failure or vasculitis. Late diagnosis worsens prognosis and leads to increased mortality. 111579 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Congenital Anomaly Type Single Ostum of Coronary Artery with Origin in the Right Coronary Sinus NICOLAS BIONI STEFANO 1, Elisa Souza Lini2, Alexandre Quadros1, Renato Kalil1, Joao Carlos Vieira da Costa Guaragna1 (1) Hospital Divina Providencia; (2) Pontificia Universidade Catolica do Rio Grande do Sul Introduction: Coronary artery single ostium cardiac anomaly represents a rare congenital alteration of unknown etiology. This condition presents clinically from asymptomatic forms to cardiac ischemia and manifestations of sudden cardiac death, especially in young adults. The incidence of this pathology is variable, affecting 0.03% to 0.4% of patients undergoing cardiac catheterization. Case Report: Patient LVAG, 69 years old, male, hypertensive, dyslipidemic, heart failure, hypothyroidism and COPD. Hospitalized for salmonella colitis. During hospitalization, he presented anginal chest pain. He already had similar episodes at home with small efforts, with gradually worsening in the last few weeks. ECG showed sinus rhythm and septal inactive zone, there was elevation of troponin levels, being taken to coronary angiography. During evaluation, an anomalous coronary path was visualized, with the anterior descending artery and circumflex artery originating from the right coronary sinus, together with the right coronary artery. There was also an ulcerated lesion in the middle segment of the circumflex artery, but with a complicated anatomy and path to perform angioplasty. Coronary computed tomography angiography showed a malignant path of the circumflex artery, with passage between the aorta and the pulmonary artery. Echocardiogram showed mild systolic dysfunction with an ejection fraction of 42%. Heart Team defined coronary artery bypass graft surgery for definitive treatment. Conclusion: Congenital coronary artery anomalies are subdivided into seven categories, highlighting the single-ostium coronary artery anomaly, in which four paths can be followed: retroaortic, septal, anterior and interarterial. Its clinical presentation includes angina, ventricular arrhythmias, dyspnea, syncope, heart failure and sudden death. The occurrence of ischemia associated with this anomalous condition, in this case, consists of the path of the vessel between the pulmonary artery and the aorta, which would eventually suffer extrinsic compression. In the present case, the patient had an anomalous interarterial course (between the pulmonary artery and the aorta), considered a malignant type. In these cases, the patient may initially undergo coronary angioplasty and, later, surgical treatment, through reimplantation or ligation of the coronary arteries, followed by grafting of the saphenous vein or internal thoracic artery. 111591 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Chronic Total Occlusion of the Left Main Coronary Artery with Normal Left Ventricular Function and Stable Angina: A Case Report MATHEUS RAMOS DAL PIAZ1, Caio Menezes Machado de Mendonca1, Bruno Mahler Mioto1, Luis Henrique Wolff Gowdak1 (1) Instituto do Coracao (InCor) do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) Introduction: Severe stenosis of the left main coronary artery (LMCA) in patients with stable symptoms is uncommon and usually associated with a dominant right coronary artery (RCA) and rich collateral circulation. The incidence of total occlusion has been reported to be between 0.04% to 0.43%. The impact on the left ventricle (LV) function is often significant with systolic dysfunction, especially with significant involvement of the RCA. Surgical myocardial revascularization remains the best treatment for chronic total occlusion (CTO) of the LMCA. Case Report: A 69-year-old woman with hypertension, dyslipidemia, and obesity, without previous acute myocardial infarction, presented with CCS III angina, associated with dyspnea on exertion for a year. A myocardial perfusion scan revealed extensive stress-induced ischemia in the anterior, anterolateral, lateral, and inferolateral walls. A transthoracic echocardiogram showed a globally preserved ventricular function (LVEF = 65%). We found a CTO of the LMCA and a 70% stenosis of the middle RCA during an elective coronary angiography, with grade III collateral circulation from the RCA to the LMCA. The patient was admitted for surgical myocardial revascularization. A successful triple bypass was performed (left internal thoracic artery-left anterior descending artery, radial artery-left obtuse marginal branch, and saphenous vein graft-posterior descending artery). Conclusion: CTO of LMCA is a rare manifestation in patients presenting with stable symptoms. Two conditions are related to a higher probability of patient survival and maintenance of LV function: a dominant RCA without significant stenosis and an extensive collateral circulation to the left system, conditions only partially found in our patient. Despite having significant stenosis of the RCA, LV function was preserved, and the patient had stable symptoms for a year. 111598 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Report of Three Cases Submitted to Percutaneous Embolization of Pulmonary Arteriovenous Fistulas LARISSA XAVIER ALVES DE OLIVEIRA1, Debora Rodrigues1, Mauricio Lopes Prudente1, Adriano Goncalves de Araujo1, Giulliano Gardenghi1 (1) Hospital Encore Introduction: Pulmonary arteriovenous malformations (PAVMs) consist in an abnormal communication between an artery and a vein, causing clinical manifestations as chronic hypoxia or embolic events. Most cases of PAVMs are represented by hemorrhagic telangiectasia, a rare congenital disease. In the past, pulmonary fistulas were treated only by open surgery, with an expressive rate of complications. In the 70s, the first percutaneous catheter embolization was performed with coils. Currently percutaneous embolization has become the treatment of choice. We report three different cases of percutaneous correction of PAVMs using coils and vascular plugs. Cases Description: First patient, 47 years old, had an 8 mm diameter fistular sub pleural sac. Complete embolization was performed without residual shunt. The second patient, 48 years old presented a pulmonary fistula associated with chronic hypoxemia. The fistula came from several branches of the right pulmonary artery. After embolization was shown immediate improvement of central oxygen saturation. Third patient, 30 years old, the PAVM had a pseudoaneurysm raising next to the first branches of the left pulmonary artery to the upper lobe of the left lung, and two important fistulas in the right inferior lobar arteries forming a shunt right to left. Embolization of the PAVM and pseudoaneurysm was performed successfully. Conclusion: The percutaneous treatment of PAVMs is effective and safe in these cases. 111629 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Early Hemorrhagic Pericarditis After Thrombolisys in Acute Myocardial Infarction: A Case Report CAIO MENEZES MACHADO DE MENDONCA1, Matheus Ramos Dal Piaz1, Antonio Carlos Fonseca de Queiroz Filho1, Matheus Barbosa Gastaldo1, Luis Henrique Wolff Gowdak1 (1) Instituto do Coracao (InCor) do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) Introduction: Post-myocardial infarction pericarditis occurs in approximately 5% to 6% of patients who receive thrombolytic agents. It develops in the first 2 to 4 days following infarction, mainly in the first 24 hours, and usually produces only mild symptoms. Nonetheless, rare complications include hemopericardium, cardiac tamponade, and constrictive pericarditis. Treatment is primarily supportive, with appropriate use of nonsteroidal anti-inflammatory agents. However, pericardiocentesis is indicated to treat a large pericardial effusion, particularly if accompanied by tamponade. Case Report: A 63-year-old male patient with a history of hypertension and smoking was transferred to our hospital 24 hours after an extensive anterior ST-elevation myocardial infarction (STEMI). The patient was initially treated in another facility with ASA + clopidogrel and underwent thrombolysis with tenecteplase, with signs of reperfusion. The patient was brought to the cath lab, significant 3-vessel disease was found, and surgical myocardial revascularization was recommended. Clopidogrel was withdrawn, and full anticoagulation with enoxaparin was initiated. The patient remained asymptomatic, but a transthoracic echocardiogram on the second-day post-MI revealed a pericardial effusion of 25 to 30 mm with signs of ventricular filling restriction with no evidence of left ventricular (LV) dysfunction or LV free wall rupture. The patient developed severe hypotension on the same day, requiring vasoactive drugs. Urgent pericardiocentesis was performed, and 900 mL of hematic fluid was recovered. Right after, the patient evolved with significant hemodynamic improvement. Histopathological examination of a pericardial fragment revealed the diagnosis of acute fibrinohemorrhagic pericarditis. Conclusion: Acute hemorrhagic pericardial tamponade after infarction rarely occurs, at a reported incidence of only 1% of STEMI patients treated by thrombolysis, often within the first 24h. Despite being a rare complication, the present case calls attention to the fact that hemopericardium and cardiac tamponade can occur in patients who have suffered an acute MI and should be included in the differential diagnosis in those presenting with hemodynamic instability. Prompt echocardiography assessment may lead to early diagnosis and better outcomes in these patients. 111883 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Right Ventricle Intracardiac Mass of Unknown Origin Presenting as Right-Sided Heart Case Report MAYARA DE SOUZA VASCONCELOS1, PEDRO RAFAEL VIEIRA DE OLIVEIRA SALERNO1, LUCIA MARIA VIEIRA DE OLIVEIRA SALERNO1, EVELINE BARROS CALADO1 (1) HOSPITAL DAS CLINICA DA UNIVERSIDADE FEDERAL DE PERNAMBUCO Introduction: Intracardiac masses are rare. Causes include neoplasic and non-neoplasic conditions. Diagnosis is challenging due to nonspecific clinical presentation and commonly occurs incidentally. Echocardiography (ECHO) is usually the initial method of assessing the size, location, fixation, mobility, and hemodynamic repercussion of the mass. Computed tomography (CT) and magnetic resonance imaging (MRI) further complement the mass evaluation. Case Description: A 54-year-old female presented with facial edema and conjunctival hyperemia that progressed to diarrhea, lower limbs edema, ascites, abdominal pain, jaundice, and dyspnea at moderate efforts. After a syncopal event with no post-ictal period, she was admitted for investigation. Past medical history included a stroke in 2019 and schistosomiasis that was treated in 2000. After admission, discrete leukocytosis, with significant eosinophilia, elevated C-reactive protein, high aminotransferases, and high lactate dehydrogenase were identified. Blood cultures were negative. Urine culture was positive for Escherichia coli and ceftriaxone + metronidazole were initiated. Transthoracic and transesophageal ECHOs displayed a large right ventricle (RV) mass that occupied most of the chamber and was attached to the tricuspid valve (TV), enlargement of the right atrium, inferior vena cava, and hepatic veins were also seen. Cardiac MRI confirmed the mass that measured 21 x 28,5 x 33,4 mm, attached to the TV and projecting towards the RV outlet. Metastatic disease screening with imaging studies provided non-significant findings. Lower limbs USG with Doppler identified bilateral deep venous thrombosis. Tumor markers and investigation for thrombophilia and collagen disease were negative. Cardiac surgery for the removal of the mass was done, intraoperative findings included a mass involving the papillary muscles and the leaflets of the TV with a caseous appearance. After excision, a biologic prosthesis was inserted in TV position. Histopathological analysis showed a material containing fibrin and leukocytes, and endomyocardial necrosis without significant eosinophil infiltration--no signs of neoplasia, bacteria, or fungus. After discharge, previous blood tests were identified and showed chronic fluctuating eosinophilia (largest count 4.190/mm3, 27,3%). Conclusion: Unique features of this case are the large thrombus-like RV mass causing obstructive symptoms and the presence of persistent eosinophilia perhaps suggesting Loeffler's endocarditis. 111622 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Evolution of a Case of Serratia Marcescens Endocarditis - The Role of 3D Transesophageal Echocardiography THIAGO BURIL FONTES1, Pedro Henrique Pereira Inglez1, Rudyney Azevedo1, Cassia Cardoso Costa1, Carolina Frezzatti de Andrade Neves1 (1) Hospital do Servidor Publico Municipal de Sao Paulo Introduction: Infective endocarditis (IE) is a cardiovascular disease. The etiology is predominantly gram-positive cocci, but it has other infectious agents: HACEK group, fungi and other atypical germs. IE caused by Serratia marcescens is rare, documented in less than 1% of cases. Pathophysiology is multifactorial. Case Report: E.G.V., 58 years old, history of aortic valve disease due to rheumatic fever and permanent pacemaker (PM). PM, on 03/05/22, evolving after ten days of the exchange with phlogistic signs, fever and fluctuation in the generator store region. Opted for cleaning the PM pocket with secretion collection for culture. Febrile peaks remained,37.7degC, after PM cleaning. White blood cell 13 (4.8-10.8) with absolute neutrophils of 11 (1.4-6.5). Cultures with the presence of Serratia marcescens in secretion of PM store and in blood culture. Treatment for bloodstream infection with Meropenem and Teicoplanin. The electrodes were then removed from the PM, with laser, and sent for culture. In the culture, 04/01/22, there was growth of Serratia marcescens on PM electrodes. Because of this, a 2D TEE was performed, showing a mass adhered to the tricuspid valve, which may correspond to vegetation. Changed Daptomycin and maintained Meropenem. The definitive PM generator implanted on 04/19/22, maintaining afebrile condition on the 6th PO and obtaining negative results from the 6 control blood cultures. 3D TEE was performed on 05/11/22 showing persistence of the image of the mass in the right ventricle, this time being interpreted as a residual image due to the removal of the PM. Conclusion: It is a rare case of Serratia marcescens infection and the challenge of interpreting an image of an intracardiac mass, the 3D TEE can help in the follow-up of the case. 111626 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Aortoesophageal Fistula in Post-Operative Dissection of Chronic Ascending and Descending Aorta: A Case Report SABAH ABAZAR YOUSIF MOHAMED ALI1, Paulo Rafael Goncalves da Silva Von Zuben1, Gabriel Queiroz de Abreu1, Ricardo Ribeiro Dias2, Georgina del Cisne Jadan Luzuriaga2 (1) Centro universitario Sao Camilo (CUSC); (2) Instituto do coracao do Hospital das Clinicas (InCor-HC) Aortic dissection is a disease, which presents with chest discomfort, acute hemodynamic compromise and high risk of mortality, requiring surgical management, with endovascular repair of the aorta. However, the prosthesis used in the procedure can be considered a possible etiology of aortoesophageal fistula. LF, female, 64 years old, with a history of systemic arterial hypertension (SAH) for 6 years, hysterectomy for 30 years, with diagnostic hypotheses of aortic aneurysm and chronic dissection of the ascending aorta (55 mm) and descending (50 mm). Replacement of the aortic branch and reimplantation of supra-aortic island branches was performed. Three months after the first surgery, the patient reported daily low-grade fever, malaise, dyspnea on minor exertion, and hyporexia for two months, in addition to hemoptysis, cough, and diffuse chest pain. According to tomography angiography, a large thrombus was identified in the aorta associated with a dissection blade in the abdominal aorta, from the celiac trunk to the bifurcation, extending along the entire length of the superior mesenteric artery. Upper gastrointestinal endoscopy (UGE) showed ulceration in the esophagus with a fistulous orifice in the upper thoracic esophagus. An aortic endoprosthesis was implanted. Two weeks after the second surgery, the aortoesophageal fistula was repaired. The surgeries were a success, however, the patient developed urinary tract infection, acute respiratory failure, pneumothorax, bacteremia and acute kidney injury. The condition evolved with septic shock due to mediastinitis caused by Pseudomonas aeruginosa due to the aortoesophageal fistula, resulting in death. In the literature, aortoesophageal fistula in the postoperative period of chronic aortic dissection is rarer than aortic dissection. Based on the findings of this study, it was possible to observe the severity of such a complication, such as mediastinitis secondary to bacterial infection, which rapidly progresses to death. The situation reported, similarly to previous studies, describes presentations with the same outcome of death, which had some factors similar to that of this patient, such as chronic dissection, uneventful postoperative period and need for reintervention. Patient with an uncommon complication of aortoesophageal fistula after correction of chronic aortic dissection, however, with extreme severity of infectious complications, such as mediastinitis and death. 112133 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Anomalous Origin of Right Coronary Artery and Malignant Path with Late Repercussion: Case Report ANAIS CONCEPCION MARINHO ANDRADE DE MOURA1, Citara Trindade de Queiroz1, Dr. Marcos Antonio Ferreira Lima2, Dr. Marcel Delafiori Hikiji2, Dra. Aline Hofmann Baiao2 (1) Universidade Potiguar; (2) Hospital do Coracao de Natal Introduction: The coronary arteries' anomalous origin is rare, with a frequency of reported cases of 0.64% in neonates and 0.17% in asymptomatic children and adolescents who were discovered through an echocardiogram. Its late discovery may occur in symptomatic patients with hemodynamic repercussions, therefore, early intervention is necessary and performed with surgical correction. Case Report: A 69-year-old female, diabetic, hypertensive, and with chronic coronary artery disease was diagnosed with an anomalous origin of the right coronary artery (RCA) with a malignant path. Symptoms of typical angina and recurrent syncope started in 2012. In 2013, after an anginal condition, she underwent an elective angioplasty, with a complication that led to coronary dissection and brief cardiorespiratory arrest, requiring implantation of 2 stents in the proximal third and mean RCA, however, the artery anomaly was not described in the procedure report. Even after the intervention, the patient maintained the same clinical picture with optimized therapy for 9 years. After a coronary angiotomography in 2021, the anomalous origin of the RCA emerging in the upper portion of the left coronary sinus and its interatrial course, associated with ostial cleft compression, was described, and then coronary artery bypass graft surgery was indicated. The surgical approach was performed in 2022, through an aortic bypass graft to the middle third of the RCA and closure of its proximal third, where the previous stent was located. The patient developed with a total improvement of angina and syncope. Conclusion: Patient with a rare ACD anomaly with a malignant path, which was only discovered when she was elderly, because of symptoms of ischemia that occurred through compression of the artery, which passed between the ascending aorta artery and the pulmonary trunk artery, during ventricular systole. It is worth emphasizing the importance of early diagnosis and therapeutic intervention for better patient survival because of the high risk of sudden death. 111646 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Evolution of Coronary Thromboaspiration: Penumbra CAT RX System MURYELLE ROSA COELHO1, Rogerio Las Casas1, Vinicius Daher Vaz1, Fabricio Las Casas1, Tannas Jatene1 (1) Hospital do Coracao Anis Rassi (HCAR) Introduction: Acute Myocardial Infarction (MI) occurs due to atherosclerotic plaque rupture, and consequent coronary thrombosis. A large amount of intracoronary thrombus is a challenge for the interventional cardiologist as it difficult to restore TIMI III flow and predisposes embolization to distal microcirculation (no-reflow). Coronary thromboaspiration reduces the thrombotic load, improves coronary perfusion and reduces fibrosis area. Case Description: Male, 72 years old, smoking history, hypertension, dyslipidemia, diabetes mellitus and chronic kidney disease. Admitted at emergency room with ST-segment elevation myocardial infarction on inferior wall and 7-hour pain. A loading dose of acetylsalicylic acid and ticagrelor was administered followed by cardiac catheterization that revealed acute total occlusion in the middle third of the right coronary artery. After balloon recanalization, high thrombotic load was observed. A glycoprotein IIbIIIa inhibitor was administered, followed by unsuccessful conventional mechanical thrombus aspiration and TIMI I distal flow. In the face of failure, a Penumbra CAT RX mechanical thrombus aspiration system was used. It contains a catheter with a larger internal lumen and coupled to a pressure aspirator, unlike the conventional modality that uses a manual suction syringe system. TIMI III flow was reestablished and drug-eluting stent was successfully implanted, followed by transfer to the coronary care unit. The evolution was uneventful, echocardiogram showed preserved ejection fraction and inferior wall hypokinesia. Hospital discharge after four days of hospitalization, using dual antiplatelet therapy, statin and beta-blocker. Conclusions: Although TAPAS trial suggests a reduction in major cardiovascular events with routine mechanical thrombus aspiration in MI, larger randomized trials such as TASTE and TOTAL turned this therapy a class III recommendation, because it did not demonstrate clinical benefits and increased the risk of stroke. As the favorable results of mechanical thrombus aspiration on TOTAL trial subgroup with high thrombotic load, the Penumbra CAT RX system was developed. This system contains features as continuous vacuum, making aspiration more effective and with a lower incidence of stroke. The ongoing CHEETAH trial exclusively evaluates patients with high thrombotic burden using the Penumbra CAT RX, as in the case described, to answer the real benefit on mechanical thrombus aspiration. 111654 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Type a Aortic Dissection (Stanford) in the 36th Week of Pregnancy: Case Report of a Multidisciplinary Emergency RAMON OTT VARGAS1, Elisa Ito Mendes de Andrade1, Jose Carone Filho1, Assad Miguel Sassine1, Jose Carone Junior1 (1) Hospital Evangelico de Vila Velha Introduction: Acute aortic dissection is a rare, but lethal entity during pregnancy. Difficulties in early diagnosis and small number of studies available in this group of patients are complicating factors. Case Description: Female, 30 years old, hipertensive, at 35 weeks 6 days of pregnancy, coming from high-risk pregnancy referral service, where she was hospitalized due to restricted intrauterine growth. One week after admission, she developed severe chest pain and syncope. Electrocardiogram and lab work showed no myocardial ischemia. Transthoracic Echocardiogram was performed, suggesting ascending aortic dissection affecting the aortic valve, with mild regurgitation. A computed tomography scan confirmed the diagnosis of Stanford type A aortic dissection. Patient was transferred for cardiovascular surgery, accompanied by all the necessary equipment and medical personnel to perform emergency delivery. Admitted to this service with chest pain, using sodium nitroprusside. In the operating room, patient was submitted to orotracheal intubation with care to avoid cardiorespiratory depression of the fetus. Emergency C-section was performed, neonate with good vitality, Apgar 8/9. Immediately after the C-section, aortic surgery began. Dissection of the common carotid artery was performed for arterial cannulation. Deep hypothermia was induced in the patient. After aortotomy, a dissection flap was detected in the non-coronary sinus. The diseased aortic segment was excised, and both ends were reinforced with teflon matresses, and ultimately anastomosed to one another, obtaining excellent results. Patient resumes spontaneous rhythm after opening of the aortic clamp. Cardiopulmonary bypass time was 100 minutes and aortic cross clamp was 80 minutes. Patient developed sinus tachycardia and hypertension, requiring use of beta-blockers and intravenous vasodilators. Extubated after 48 hours. Patient progresses well, discharge from the Intensive Care Unit on the 6th day after surgery and hospital discharge seven days later. Conclusion: Despite the dismal diagnosis of acute type A aortic dissection in pregnancy and the challenges of keeping both mother and fetus alive in the context of a complex surgery such as the one described, both the patient and the neonate showed good outcome after the approach. Accurate diagnosis and timely multidisciplinary action were decisive for the result obtained in this case. 111663 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Staged Hybrid Approach for Treatment of Very High Risk Octogenarian Patient JOSE CARONE FILHO1, Roberto Ramos Barbosa1, Elisa Ito Mendes de Andrade1, Ramon Ott Vargas1, Roger Alain Pantoja Ribera1 (1) Hospital da Santa Casa de Misericordia de Vitoria - ES Introduction: Acute cardiac failure is a high mortality syndrome with varied ethiology. Mitral regurgitation following acute coronary syndrome is one of its causes and necessary management requires exceptional attention to haemodynamic patient balance. This paper describes the in-hospital events of a patient on which a intra-aortic ballon pump was implemented, after acute mitral insufficiency and cardiogenic shock, until surgery for valve replacement. Case Description: Woman, 84 years old, hypertensive, presenting with oppressive chest pain, radiating to the jaw, even at rest. Physical exam: diaphoretic, regular general state. Irregular cardiac rhythm, normal S1 and S2, holosystolic murmur heard on cardiac apex (2+/6+). Pulmonary auscultation with bilateral rales, respiratory rate of 32 and pulse oximetry saturation of 76%. Acute miocardial infarction (without elevated ST segment) was diagnosed (Killip 3, Timi Risk 4). Transthoracic echocardiography (TTE) was performed and showed chordae rupture resulting in severe regurgitation. Left ventricular ejection fraction was 62%. Patient evolved with cardiogenic shock, respiratory failure with endotracheal intubation, requiring vasopressor. Case was discussed between a multidisciplinary team and intra-aortic balloon pump (IABP) implantation was indicated for salvage and support for percutaneous coronary intervention. Patient was at hight operative risk at that moment (EuroSCOREII: 28%). On the eighth day after admission, percutaneous coronary intervention was performed, with implantation of 3 stents (anterior descending, circumflex and right coronary arteries). After 20 days in-hospital, mitral valve replacement surgery was performed, and a bioprosthesis (size 29) was implanted. IABP was removed after termination of cardiopulmonary by-pass. Patient was discharged 40 days after admission. Control TTE showed functioning bioprosthesis and no sign of intracavitary thrombus. Patient is clinically well, receiving optimized medical therapy and no signs of decompensation. Conclusion: Presence of increasingly high risk patients with multiple comorbidities and complex conditions is rising by the day in our Cardiology practices. This case shows how staged hybrid approach can be performed in high operative risk patients obtaining satisfactory results. 111666 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Minoca: Always use Dapt? RAQUEL CRISTINA FARIAS DE MEDEIROS QUEIROZ1, Barbara Mariana dos Santos Silva1, Isly Maria Lucena de Barros1, Rafael Dayves Medeiros de Queiroz1, Suellen Lidia da Silva Barbosa1 (1) Pronto Socorro Cardiologico de Pernambuco - PROCAPE/UPE Introduction: Some patients presenting with ST elevation myocardial infarction had a syndrome named myocardial infarction with non-obstructive coronary arteries (MINOCA). This diagnosis requires an AMI and absence of obstructive CAD on angiography and may present with or without ST segment elevation on the ECG. Thrombosis may be a mechanism and the prevalence is low. It may arise from thrombotic disorders, atherosclerotic plaque disruption or coronary dissection with associated thrombosis or coronary emboli. To aid in diagnosis, we can use angiography with intravascular ultrasound or OCT (40% of patients with MINOCA have some evidence of plaque disruption). In this scenario, the inpatient treatment usually involves anticoagulation and the outpatient treatment may vary depending on the underlying etiology, but we know that DAPT (dual antiplatelet therapy) may be useful in those cases where plaque disruption is possible. Case Report: Male patient, 39-year-old, with no previous comorbidities and denying the use of illicit substances or medications. He sought emergency care complaining of intense retrosternal pain, which had started forty minutes before, associated with sweating and vomiting. Electrocardiogram showed ST-segment elevation in anterior leads. The patient was referred for invasive stratification and received DAPT. The coronary angiography showed an image suggestive of thrombus presence in the proximal segment of the anterior descending artery, with Thrombolysis in Myocardial Infarction - TIMI 2 - distal flow, and all the vessels were free of significant stenosis. It was decided not to perform a percutaneous intervention at that time; abciximab was administered by 24 hours and anticoagulation was maintained with unfractionated heparin, as well as the concomitant use of DAPT. The new catheterization ten days later did not reveal the same image compatible with thrombus presence and showed a small plaque in the same proximal segment of the anterior descending artery. He showed clinical improvement and was discharged with a prescription of DAPT. Conclusion: This case illustrates the importance of identifying the causes of MINOCA to facilitate more definitive and specific treatment strategies, such as the use of DAPT. Multimodality imaging with OCT and CMR can help in our understanding of the underlying pathophysiological mechanisms within and beyond the context of coronary atherosclerotic disease, however, are not available in our practice. 111687 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Coronary Computed Tomography Angiography in the Evaluation of Kawasaki Disease Aneurism GABRIELA RIBEIRO PRATA LEITE BARROS1, Juliana Pato Serra Souza1, Kevin Rafael De Paula Morales1, Jurgen Beuther1, Diana Rodrigues de Araujo1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. Introduction: Kawasaki disease (KD) is an acute vasculitis that preferentially affects medium-sized arteries, particularly the coronary arteries. Patients with coronary artery aneurysms (CAA) are at risk for cardiac events including coronary artery thrombosis or stenosis, myocardial infarction and death. Coronary computed tomography angiography (CCTA) has been shown to be superior to echocardiography for the detection of CAA in distal portions of the vessel. It also a reliable modality for follow-up of CCA, with close correlation with catheter angiography. Case report: A 9-year-old patient with previous diagnosis of kawasaki disease treated with immunoglobulin and history of giant coronary aneurism seven years ago, presented to the pediatric cardiology consult complaining of chest pain on exertion. Previous CCTA showed coronary dilatation in of the right coronary artery (RCA) measuring and left anterior descending artery (LAD), both without luminal reduction. A new CCTA was performed. The LAD showed a large aneurysmal dilatation in the proximal segment, measuring 10 x 10 mm with proximal luminal evaluation limited by intense calcification . The RCA showed a fusiform aneurysmal dilatation measuring 8 x 7 mm, with mural thrombi and diffuse parietal calcifications, highlighting an area of critical luminal reduction right at the origin of the aneurysm . Cardiac catheterization was performed, proving significant luminal reduction in RCA, and balloon angioplasty was successfully performed. Conclusion: Aneurysms in Kawasaki Disease can evolve with difficult-to-treat stenosis. Coronary computed tomography angiography is an attractive alternative to catheter angiography for the assessment of coronary manifestations of the disease. 111690 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Extrinsic Compression of the Left Main Coronary Artery by Pulmonary Artery as Cause of Chest Pain in a Young Patient with Pulmonary Arterial Hypertension LARISSA MARIA VOSGERAU1, Roberto de Avila Martins1, Pedro Felipe Gomes Nicz1, Paulo Roberto Cruz Marquetti1, Eduardo Leal Adam1 (1) Hospital de Clinicas da Universidade Federal do Parana (HC-UFPR) Introduction: Chest pain in patients with pulmonary arterial hypertension (PAH) is usually attributed to the imbalance oxygen supply demand to the right ventricle, which can lead to subendocardial hypoperfusion. It is known that the pulmonary artery (PA) can induce extrinsic compression of the left main coronary artery (LMCA) in these patients, and it is described that a PA trunk greater than 40 mm in diameter with typical angina is correlated with compression of LMCA in most patients. This luminal reduction can lead to acute myocardial infarction, left ventricular dysfunction, arrhythmias and even sudden death. The evaluation of coronary arteries is often not performed routinely in these patients, so the incidence of LMCA compression by the PA is not well established in literature. There is no consensus about the best therapeutic strategy, but percutaneous coronary intervention is a viable option to relief symptoms and improve outcomes with a high success rate. Case Report: A 30-year-old female patient diagnosed with idiopathic PAH for 9 years and with optimized treatment seeks medical service for progressive chest pain with minimal efforts and quality-of-life impairment. During investigation, a coronary computed tomography was performed and showed a 56 mm PA trunk with a left main coronary artery ostial angulation (17.9deg) and significant luminal reduction (>70%) due to extrinsic compression (figure 1). Coronary angiography shows a critical stenosis in the LMCA. A percutaneous angioplasty with implantation of two drug-eluting stents (stent-in-stent) was successfully performed and the patient evolved with complete improvement of chest pain after revascularization. Treatment of PAH was associated with dual antiplatelet therapy with subsequent outpatient reassessment. Conclusion: Extrinsic compression of the LMCA should be considered as a differential diagnosis in patients with PAH and angina, especially in patients with a PA trunk greater than 40 mm. Percutaneous coronary intervention is a safe and effective option to improving symptoms and reduce cardiovascular outcomes with a low rate of complications. 111725 Modality: E-Poster Young Researcher - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Coronary Embolism - Challenges in Diagnosis and Treatment MATHEUS BURIGO OLIVEIRA1, Gisele Messias Mattioli1, Fernanda Nascimento Dourado1, Leticia Macacchero Moreirao1 (1) Instituto Nacional de Cardiologia Introduction: Coronary embolism is a rare cause of myocardial infarction (MI). Unlike type I MI (plaque instability), its pathophysiology and etiology are not yet well defined. Some studies show it is the underlying cause of 3% of MI, but often neglected. Case Report: A 31-year-old male diagnosed with dilated cardiomyopathy and hypertension was admitted with typical chest pain and Q waves in leads V1-V6 on the electrocardiogram and submitted to coronary angiography, which showed thrombi in the left anterior descending artery and second diagonal branch without other obstructive lesions. Investigation ruled out the presence of risk factors for atherosclerosis (coronary calcium score 0 and normal lipid profile), left ventricular thrombus, atrial fibrillation and paradoxical embolism. Research for thrombophilia showed antinuclear antibodies (ANA) 1:180 of pathological pattern (nucleolar homogeneous) which did not meet the criteria for diagnosis of lupus or antiphospholipid antibody syndrome (APS). We opted for conservative therapy with enoxaparin 1 mg/kg twice a day. A new coronary angiography 1 week after therapy showed a considerable reduction in thrombi. Conclusion: MI caused by coronary embolism should be considered in young patients with few risk factors for atherosclerotic disease. This case illustrates the need to search for triggers of this event, notably arrhythmias, severe left ventricular dysfunction, thrombophilia and rheumatological diseases. The lack of randomized trials on this subject makes it difficult to decide on the type of anticoagulation and the duration of therapy. Finally, the underlying diagnosis is impaired by acute MI either by changes in the coagulation cascade or by the need for rapid use of anticoagulation, which may alter the results of laboratory tests. 111737 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Dilated Cardiomyopathy with Reduced Ejection Fraction Secondary to Rheumatic Myocarditis ARMINDO JREIGE JUNIOR1, Karen Katchvartanian1, Luis Henrique Silveira Moreira1, Renan Cintra de Alvarenga Oliveira1, Bruno Biselli1 (1) Instituto do Coracao do Hospital das Clinicas da FMUSP (InCor/HCFMUSP) Introduction: Rheumatic fever is a possible late complication secondary to group A streptococcus infection. Repeated episodes of acute outbreaks can progress to rheumatic heart disease, which is associated with significant morbimortality in children and young adults. Case Description: A 46-year-old male patient with history of rheumatic fever underwent valve replacement with a caged-ball metallic prosthesis in 1992 due to combined aortic stenosis and regurgitation. He remained asymptomatic until 2020, evolving after that with symptoms of heart failure (HF). The initial hypothesis was dysfunction of the metallic prosthesis. Transesophageal echocardiogram did not reveal prosthetic alterations, showing the presence of ventricular dysfunction, reduction of ejection fraction to 25% (previously normal), dilatation of left cavities and areas of segmental alteration. Coronary angiography showed no obstructive lesions and serology for Chagas disease was negative. Magnetic resonance imaging (MRI) of the heart showed areas of late transmural enhancement in the apical and subendocardial segments in the lateral, anterior and middle wall segments. In view of the MRI findings and the previous diagnosis of rheumatic fever, the main hypothesis was active rheumatic myocarditis. Gallium-67 scintigraphy identified the presence of increased uptake in a projection of the cardiac area with a diffuse pattern and mild degree. This result corroborated the existence of an active cardiac inflammatory process. Patient currently under outpatient follow-up, undergoing clinical evaluation for corticosteroid therapy or inclusion in the heart transplant waiting list. Conclusions: The treatment of rheumatic carditis lacks consensus, with little evidence. Regarding the diagnosis and treatment of rheumatic myocarditis, the scenario is even worse, with only a few observational studies. The therapy currently proposed for severe and refractory cases, as described, is based on the use of corticosteroids. There is great variation between the data in the literature, related to the dosage of the drug to be used, treatment duration and associated pulse therapy. Heart transplantation is also a possibility for cases of terminal and refractory HF. Due to the high prevalence of rheumatic fever in our country and the clinical severity associated with rheumatic myocarditis, further studies must be done for adequate therapeutic management and reduction of morbimortality secondary to this clinical entity. 111742 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Cardiac Complications After SARS-CoV-2 Infection CAROLINA RESENDE MARIZ1, Catharina de Almeida Serra Faria1, Julia Colonese Serra1, Viviane Campos Barbosa de Sena1, Joaquim Marcio Duarte e Silva1 (1) INSTITUTO NACIONAL DE CARDIOLOGIA Introduction: Since the beginning of SARS-CoV-2 pandemic in 2020, several consequences resulting from this infection have been reported, including myocarditis. The mechanism's of myocardial injury are not fully understood yet, but seems to be related to direct damage to cardiomyocytes, systemic inflammation, interstitial fibrosis, mediated immune response, and exaggerated cytokine response. Case Description: G.D.M, male, 4 months old, previously healthy, admitted to Intensive Cardiac Unit in acute congestive heart failure, requiring invasive mechanical ventilation, inotropic and diuretic support for 15 days. Echocardiogram revealed severe mitral insufficiency, left ventricular(LV) dilation and severe dysfunction, with ejection fraction (EF) of 18%. Angiotomography ruled out coronary artery anomalies and cardiac resonance magnetic revealed evidence of myocarditis. Laboratory tests showed elevated BNP, D-dimmer as well as troponin. SARS-CoV-2 PCR and IgM were negative, but SARS-CoV-2 IgG was positive. Also, respiratory syncytial virus and Influenza PCRs were also negative. After the diagnosis of Myocarditis related to SARS-CoV-2 infection was made, therapy with immunoglobulin, enoxaparin and acetylsalicylic acid was initiated. After this therapy, the patient improved clinically as well as laboratory and was discharged with medications. Follow up made with echocardiogram at 2 months showed significant LV dilation, with only mild improvement of EF (Teicholtz and Simpson, respectively, 27% and 24%). Conclusion: Pediatric post viral myocarditis usually has a benign and self-limited course, but in some cases, it results in severe cardiac dysfunction. Given the ongoing pandemic, patients with cardiovascular dysfunction should raise suspicion for SARS-CoV-2 infection and its complications. 111744 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Multilobulate Left Ventricular Pseudoaneurysm in Late Mitral Valve Replacement GABRIELA RIBEIRO PRATA LEITE BARROS1, Juliana Pato Serra Souza1, Kevin Rafael De Paula Morales1, Max Walter Reyes Barrenechea1, Eduardo Kaiser Ururahy Nunes Fonseca1 (1) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. Introduction: Left ventricular pseudoaneurysm (LVP) results from a cardiac-free wall rupture contained by adherent pericardium or scar tissue without any involvement of myocardium or endocardium. It frequently occurs in the setting of myocardial infarction, cardiac surgery and endocarditis. Patients with LVP can report symptoms of heart failure, dyspnea, or chest pain. Left ventriculography is the gold standard for diagnosis, but coronary computed tomography angiography has been increasingly used as noninvasive diagnostic technique. Case Report: A 68-year-old female patient, with a previous history of mitral valve replacement, developed dyspnea and atypical chest pain. During investigation, a transthoracic echocardiogram was performed and showed an oval image with flow inside and aparent communication with the right atrium. Heart and coronary tomography showed a multiloculated pseudoaneurysm (*) with origin in the basal inferoseptal wall of the left ventricle, close to the mitral valve prosthesis. This formation maintained ample contact with the middle and distal segments of the right coronary artery, measuring about 64 x 32 x 27 mm. The image corresponded to a left ventricular pseudoaneurysm of apparent late postoperative etiology, determining compression of the of the venous sinus and in intimate communication with the right coronary artery. Conclusion: Heart and coronary computed tomography is a non-invasive method for diagnosis and evaluation of LVP. 111768 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Complications of Lutembacher Syndrome: A Case Report CAROLINA JANUARIO DA SILVA1, Diana Patricia Lamprea Sepulveda1, Flavio Hilton Feijo Cavalcanti Silva1, Raquel Cristina Farias de Medeiros Queiroz1 (1) PRONTO SOCORRO CARDIOLOGICO DE PERNAMBUCO - PROCAPE Introduction: Lutembacher Syndrome (LS) is a rare condition and is defined as a combination of ostium secundum atrial septal defect (ASD) and mitral valve stenosis and both can be congenital or acquired. The hemodynamic repercussions of this syndrome result from the severity of the valve stenosis and ASD sizes. This can lead to numerous symptoms and complications, such as intolerance to exertion, palpitation, pulmonary hypertension, left atrium and right chamber dilatation, atrial arrhythmias and tricuspid valve failure. The treatment can happen through open surgical correction (with ASD closure and mitral commissurotomy or valve replacement) or percutaneous therapy (with balloon mitral valvuloplasty and septal occlusion with a prosthetic device) in eligible patients. We report a case in a mild age male, with late diagnosis and complicated by atrial fibrillation and pulmonary hypertension. Case Report: Male patient, 46-year-old, with previous diagnosis of systemic arterial hypertension. In 2011, he sought emergency care complaining of dyspnea on exertion and orthopnea. The echocardiogram showed an important mitral stenosis; ostium secundum atrial septal defect with a shunt from the left atrium to the right atrium; preserved left ventricle function and moderate left atrium dilatation. Based on the clinical and imaging findings, LS was diagnosed and was opted for the isolated mitral valve repair, with subsequent correction of interatrial communication - which occurred in 2013. In april 2022, the patient was hospitalized for the same symptoms he had 11 years before. The new echocardiogram showed mitral valve with reduced opening and thickened cusps, average gradient of 5 mmHg and valvular area calculated by the planimetry of 1 cm2, representing an important mitral stenosis associated with a moderate mitral regurgitation; important left and right atrium dilatation; preserved left ventricle function and a moderate pulmonary arterial hypertension (with pulmonary artery systolic pressure estimated at 47 mmHg). The electrocardiogram showed a previously unknown atrial fibrillation. Clinical treatment was optimized and the patient was referred for mitral valve replacement. Conclusion: Early diagnosis with correction of mitral stenosis and closure of ASD indicate a good prognosis. However, in the cases that the diagnosis occurs late, the presence of heart failure, atrial fibrillation and pulmonary hypertension is more common and the prognosis is reserved. 111776 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Aneurysmal Dilation of the Coronaries: A Case Series CAMILA DALCOMUNI DOS SANTOS1, Rafael Vieira Fernandes1, Airton Salviano de Sousa Junior1, Igor Henrique Silva Leite1, Barbara Porto Valente1 (1) Instituto Dante Pazzanese de Cardiologia - IDPC Aneurysmal dilation of the coronaries arteries has a prevalence rate between 1-3%(1). It can be classified in aneurism or ectasia. The first, defined as a focal dilation of about 1.5x the normal diameter and the second as a diffuse dilation The right coronary is the most targeted with 40% of cases, followed by 32% of the left anterior descending (2). Fifty percent are associated with atherosclerosis, the rest is caused by congenital anomalies and inflammatory diseases, such as Kawasaki's (1). Most are clinically silent and are only detected incidentally during coronary angiography or computed tomography. Due to the lack of evidence, management is challenging. Usually, these patients are more susceptible to presenting complications like local thrombosis, distal embolization and myocardial infarction (5). The use of anticoagulants in the context of the acute coronary syndrome (ACS) is implicated in the reduction of major adverse cardiovascular events (MACE) in observational studies. Similar evidence sustains the use of dual antiplatelets (2,4). We present here a serie of 9 cases with aneurysm/coronary ectasia with median follow up of 3,5 years. All 9 patients had Myocardial infarction with non-obstructive coronary artery, 7 with ST-Elevation, due to aneurysm/coronary ectasia, of which 6 were men and 3 women, median age 54,5 years. Two patients had a family history of early coronary artery disease and previous infarction. Three patients had diabetes, history of smoking and obesity. Four patients were dyslipidemic and six had history of hypertension. One patient had atrial fibrillation/Flutter. The ejection fraction ranged from 40 to 60%, with an average of 52.7%. In the treatment, all patients were using statins and beta-blockers. Regarding antiplatelet and anticoagulation of these patients, 2 were using warfarin associated with P2Y12 inhibitors (iP2Y12), 1 was using warfarin alone, 1 was using direct-acting oral anticoagulant alone, 1 was using aspirin alone, 1 was using warfarin associated with aspirin and iP2Y12, and 2 used aspirin associated with iP2Y12. One of the patients evolved with dyspneia and 3 with angina. Three patients had another ACS. No deaths were recorded. Aneurysmal dilation of coronary vessels is a challenging and misdiagnosed entity, with lack of evidence, supporting an individualized management. 111812 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Coronary Artery Vasospasm in a Patient with Chron's Disease FELIPE ROSSI LORO1, CARLOS ALBERTO CAMPELLO JORGE2, GUILHERME DE MORAES FAVERO1, GABRIELLE MOLINA PINTO1, FERNANDA FURTADO REGATIERI1 (1) UNIVERSIDADE FEDERAL DE MATO GROSSO DO SUL - UFMS; (2) Hospital Militar de Area de Campo Grande - HMILACG Vasospastic angina, also known as Prinzmetal angina, corresponds to a form of angina pectoris related to coronary artery spasm, which can lead to transient ST-segment elevation on the electrocardiogram. We documented a case of a 62-year-old male, a former smoker, with hypertension, with a history of atypical chest pain during exercise for 11 years, and a previous investigation with catheterization showing no findings. In the meantime, he was also diagnosed with Crohn's Disease due to gastrointestinal symptoms. He presented to our emergency department due to typical chest pain, which had been lasting 45 minutes and started after a positive treadmill exercise stress test for ischemia. The electrocardiogram and echocardiogram performed in the emergency room showed no abnormalities. He performed catheterization that showed severe stenoses in the right coronary and the left anterior descending arteries, but while preparing for angioplasty, the stenoses resolved after intracoronary nitroglycerin injection, thereby confirming the vasospasm. The case represents an atypical presentation of variant angina. Our hypothesis is that vascular hyperreactivity caused by Crohn's disease acted as a precipitating factor for the patient coronary spasms. 111822 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19, An Independent Cardiovascular Risk Factor? Case Report of a Patient with Rapid Progression of Coronary Artery Disease JOAO DE AZEVEDO1, Marcelo Kirschbaum1, Silvio Marques Povoa Junior1, Breno Oliveira Almeida1, Claudio Cirenza1 (1) Hospital Israelita Albert Einstein Introduction: Complications of the post-acute phase of COVID-19 can manifest in several organs and systems, mainly in the lung, but also in the cardiovascular and other organs. This is an uncommon clinical case of a patient with previous history of coronary artery disease and recent angioplasty, who was infected by COVID-19. This patient evolved with rapid and significant progression of underlying atherosclerotic disease resulting in an acute coronary syndrome and sub occlusion of the main left coronary artery. Case Report: A 58-year-old male patient was admitted to the emergency room with intermittent left arm pain, worsening on exertion and improving at rest, starting 24 hours before presentation. He had a history of coronary artery disease with elective angioplasty of the left anterior descending artery 2 months before in the context of stable angina, with no other coronary lesions. Later he had mild COVID 19 infection. He presented a dynamic change in the EKG, with ST-segment depression greater than 2.0 mm in DI, DII, AVF, V2-V6, in addition to ST-segment elevation in AVR, ultrasensitive troponin of 19 (VR <= 5). He was referred to the hemodynamics department for early invasive stratification and underwent angioplasty of the left main coronary artery due a sub occlusive lesion in that artery. Conclusion: Cardiovascular risk may increase in post-acute phase of COVID-19. This is an important issue that should draw health system attention to improve assistance either for mild or aggressive post-infection patients. 111828 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Subaortic Ventricular Septal Defect as a Complication of Native Valve Endocarditis EVELYN AMBROSANO ANTONIO1, JOSE EDUARDO DE LIMA BORRELLI FILHO1, LUCIANE FRANCISCHINI GOTTSCHALL ODONE1, FERNANDA MENDES1, VINICIUS MEARIM ODONE1 (1) HOSPITAL DOS FORNECEDORES DE CANA Despite the technological and therapeutic advances, infective endocarditis (IE) remains a pathology with high morbidity and mortality. On the other hand, there is a change in its epidemiological profile, with an increase in cases related to the presence of invasive devices and valve degeneration, with staphylococcus being the main infectious agent. We report a successful case in the treatment of a severe aortic valve IE that resulted, in addition to multiple sites of embolization and cardiogenic shock resulting from acute and severe aortic insufficiency (AOI), in coronary leaflet perforation, extensive valve abscess and consequent ventricular septal defect (VSD) subaortic COP, 73, male, with indolent lymphocytic lymphoma and non-dialytic chronic renal failure. Admitted with poor general condition, fever, abdominal pain and dizziness. Submitted to infectious screening and initially diagnosed with urinary tract infection, without improvement despite empirical antibiotic therapy. After neurological worsening, associated with septic shock of abdominal focus, multiple sites of embolization and hematogenous dissemination were visualized on tomography, including pyelonephritis, splenic abscess, cerebellar ischemia and skin lesions characterized as Janeway lesions. Identified in paired blood cultures S. Aureus infection. He underwent transesophageal echocardiography, which confirmed filamentous vegetation in a 10 mm native valve associated with valve dysfunction - moderate aortic insufficiency. On the 45th day of treatment, he presented rapid clinical deterioration to cardiogenic shock and cardiorenal syndrome, secondary to acute and severe AOI, and urgent surgical treatment was chosen. He underwent aortic valve replacement with a biological prosthesis, with intraoperative visualization of right coronary sinus perforation, extensive valve abscess and contiguity to the septum, resulting in a VSD approximately 1 cm below the aortic valve, which was corrected at the same surgical time. Maintained in intensive support and prolonged antibiotic therapy, with resolution of the infection, cardiac compensation and recovery of renal function We report the case of successful clinical and surgical treatment in a severe IE of native aortic valve, with positivity in all diagnostic criteria, multiple embolizations and rapid evolution to valve insufficiency, associated with abscess and consequent subaortic VSD, an uncommon but serious and potentially fatal local complication. 111870 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Focal Contraction Pattern in Takotsubo Syndrome: A Case Report FELIPE HADDAD LOVATO1, Arthur Antunes Silva Castro1, Maria Julia Palitot de Melo2, Isabella Secol Corteze1, Isabella Souza Oliveira1 (1) Hospital Sirio-Libanes (HSL); (2) Pontificia Universidade Catolica de Campinas (PUCCAMP) Background: Takotsubo cardiomyopathy (TCM) is a reversible left ventricular dysfunction triggered by emotional or physical stress, which closely mimics acute coronary syndrome (ACS) and can presents with chest pain and dyspnea, dynamic ST/T changes, elevated myocardial necrosis biomarkers and and regional left ventricular (LV) wall motion abnormalities, without significant coronary artery disease. It is particularly frequent in 65-70 year-old female patients and should be considered as a differential diagnosis in episodes of chest pain. We describe the case of a 69 year-old woman who presented with chest pain while under stress and was then diagnosed with a focal variant of TCM, which represents 1.5% of patients in the International Takotsubo Registry study. SUMMARY M.E., 69 year-old female, with previous diagnosis of hypertension, presented to the emergency department with a 3 hour long chest pain during emotionally stressful event. On admission, ECG showed ST-segment depression in the inferior wall and V4-V6, with asymmetric negative T-wave in V2-V3, and laboratory tests showed high troponin. With the suspection of ACS, cardiac catheterization was indicated and showed no obstructive lesions. Echocardiogram showed hypokinesia in the anterior basal region. During investigation, the myocardial MRI showed a focal akinesia of the anterior middle segment of the LV. After these findings, we diagnosed TCM with focal involvement. Conclusion: TCM is an underdiagnosed cause of chest pain. It should be considered a differential diagnosis especially in postmenopausal women presenting with symptoms similar to ACS. This cardiomyopathy is often delayed, so it is important that physicians maintain a high index of suspicion for TCM, mainly in patients with few cardiovascular risk factors. 111877 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Recurrent Left Ventricular Pseudoaneurysm Secondary to Myopericarditis - Case Report MARIANA SILVEIRA DE ALCANTARA CHAUD1, Lais Olivo Rossi1, Felipe Lopes Malafaia1, Pedro Gabriel de Melo Barros e Silva1, Mucio Tavares de Oliveira Junior2 (1) Hospital Samaritano Paulista; (2) Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Introduction: Left ventricular (LV) pseudoaneurysm is a rare disorder. It results from the rupture of the LV free wall and leads to hemorrhagic process contained by pericardium or scar tissue. LV pseudoaneurysms are most commonly caused by myocardial infarction. It can also be identified after cardiac interventions, infections or trauma. We describe a rare case of LV pseudoaneurysm secondary to myopericarditis with recurrences after first approach. Case Report: A 36-year-old man, with past medical history of hypertension, presented to our hospital with a 3-year complaint of chest pain, worsening in the last thirty days. Discomfort was described as sharp and radiated to left shoulder. It was associated to dyspnea on moderate exercion. Admission tests revealed negative troponin. Coronary computed tomography angiography (CTA) had no obstructive lesions. Echocardiogram confirmed LV pseudoaneurysm. At magnetic ressonance imaging, LV pericardial and mesoepicardial thickening was observed, with delayed enhancement suggesting myopericarditis, in addition to apical thrombus image. Coronary angiography confirmed the diagnosis, and aneurysmectomy was indicated. Surgery was uneventful and he was discharged in good condition twelve days after surgery. Five months after surgery, patient presented with chest pain and fever. Chest CTA showed a saccular formation at the apex of the LV. The patient was admitted for re-approach. Aneurysmal sac was sewn with anchored stitches and it was closed over the orifice without complications. He was discharged on the seventh postoperative day with good clinical evolution. Six months after the second intervention, patient had chest pain again. Echocardiogram showed LV rupture and communication to a neocavity with thrombus formation, which led to a new surgical approach with a vascular plug. On the fifth postoperative day, he was discharged with a well-positioned apical plug, obliterating the orifice. Six months later, a control echocardiogram was performed with an apical occluder device without shunt, apical hypokinesia and preserved LV ejection fraction. At one-year follow-up the patient remains asymptomatic and practicing physical activity. Conclusion: The case demonstrates that the presence of LV pseudoaneurysm resulting from myopericarditis, although rare, must be identified soon with multimodality tests. Surgical correction must be performed before long in order to prevent its rupture and provide quality of life for the patient. 111879 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY A Case of Tricuspid Insufficiency with Late Evolution ANA LUIZA DE OLIVEIRA QUEIROZ TEOFILO1, WILSON ANDRES MENA SILVA1, Amanda de Miranda Constantino1, Luiz MInuzzo1, Daniel Dantas1 (1) INSTITUTO DANTE PAZZANESE DE CARDIOLOGIA Introduction: Tricuspid insufficiency (TI) is thought to be a rare complication of blunt, non-penetrating chest trauma. The right ventricle (RV) is immediately behind the sternum, predisposing it to an anteroposterior compression type of injury, especially during the end diastolic phase. Case Description: A previously healthy 39-year-old male without cardiac history was admitted to the emergency room with symptoms of heart failure and atrial flutter. Transthoracic echocardiogram showed significant tricuspid regurgitation, with an image suggestive of chordae rupture related to the anterior leaflet, with significant enlargement of the right chambers (right atrium indexed volume 115 ml/m2), moderate RV systolic dysfunction. After clinical stabilization, a history of high-energy automobile trauma occurred 20 years ago was identified, which resulted in traumatic brain injury and blunt abdominal trauma, requering abdominal surgeries; did not have any cardiovascular symptoms. Since then, he has not performed any cardiovascular follow-up. However, about three years ago, after starting to practice intense sports, he noticed of fatigue and dyspnea. He noticed progression of symptoms, seeking care in the emergency room with dyspnea on minimal exertion, palpitations and chest pain. In the heart team it was indicated surgical correction for severe TI. In the intraoperative, rupture of the chordae was observed, with calcification of the related papillary muscle and significant dilation of the tricuspid ring (60 mm);he was underwent valve replacement for a biological prosthesis in the tricuspid position. Postoperative echocardiogram showed the prosthesis in tricuspid position without reflux and maximum gradient of 8 mmHg. Conclusion: We report a case of traumatic TI, manifesting symptoms 20 years after the trauma. The interval between the traumatic event and the appearance of symptoms is variable, possibly due to the variability of possible associated valve lesions. While papillary muscle rupture is associated with more severe and acute symptoms (weeks to months), chordae rupture more commonly causes a slower course -10 to 25 years. The timing and appropriate treatment of traumatic TI depends on the natural course of the disease. Most cases do not require surgical intervention in the immediate period after the event. However, in the medium and long term, surgical correction of the tricuspid valve -by replacement or valve indicated to improve symptoms and avoid permanent impairment of the RV. 111887 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Interventricular Communication After Acute Inferior Wall Myocardial Infarction with Good Clinical Outcome: A Case Report MARIANA DE PAULA PERES1, Clarissa San Thiago1, Eduardo Rosa da Silva1, Camila Bussolo Schmitt1, Evandro de Campos Albino1 (1) Instituto de Cardiologia de Santa Catarina Interventricular communication (IVC) after acute myocardial infarction (AMI) is more common after anterior wall infarction, in the apical septal region, but, less commonly, it can occur in inferior wall AMI, at the base of the septum. It is a serious and potentially fatal complication that can suddenly lead to cardiogenic shock. Female patient, 56 years old, cleaning lady, is admitted to the emergency department with burning chest pain, of strong intensity, beginning 2 hours ago, irradiated to the left upper limb. She had arterial hypertension (SAH), diabetes mellitus, dyslipidemia and obesity, in addition to being an active smoker, with early family history of acute coronary syndrome. On admission, she was hemodynamically stable, respiratory and cardiac auscultation without alterations, as well as the remainder of the physical examination. The electrocardiogram (ECG) presented a tracing with sinus rhythm and ST-segment elevations in leads referring to lower walls. Coronary angiography visualized an obstruction of the distal third of the right coronary artery (RCA). Primary angioplasty of the lesion in the RCA was successfully performed. Transthoracic echocardiogram (TTE) showed aneurysm in the inferior wall of left ventricle (LV), LV concentric remodeling, grade I diastolic dysfunction and ejection fraction preserved despite segmental myocardial involvement and mild mitral regurgitation. Five days after hospitalization, she evolved with the presence of a 4+/6+ systolic murmur in the lower left sternal border, and a new TTE was requested, which showed IVC in mid-inferobasal segment from the base of the aneurysm, neck diameter estimated in 1.5 cm and diameter of the outlet in the right ventricule estimated at 0.6 cm, with mild hemodynamic repercussion. After one day, the patient started with symptoms of pulmonary congestion and showed clinical improvement with furosemide. Correction of post-AMI IVC with bovine pericardium was successfully performed twice weeks after identification via TTE. A new TTE was performed, and showed an intact interventricular septum (IVS). Currently, the surgery is indicated even in hemodynamically stable pacientes and with preserved left ventricular function, due to the possibility of abrupt expansion of the local rupture, resulting in sudden hemodynamic collapse. The shutdown surgery remains the procedure of choice, but the timing is controversial, and it should be performed as early as possible in cases of cardiogenic shock. 111893 Modality: E-Poster Young Researcher - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Cardiac Tamponade as the First Manifestation of Systemic Histoplasmosis FLAVIA DE MORAES PEDRO MOISES1, Bernardo Cleto Teles e Silva1, Andrea Haddad1, Alessandra Godomiczer1, Joao Felipe Tamiozzo Reis1 (1) Hospital Unimed Rio Histoplasmosis is an infection caused by inoculation of the fungus Histoplasma capsulatum into soil or by dust contaminated with bird or bat feces. Prolonged and intense exposure, age and immunosuppression are risk factors. It may be restricted to the lung or spread hematogenously to other organs. Most cases are asymptomatic or mild, progressing without diagnosis. Cardiac manifestations are endocarditis, mediastinal granuloma, fibrosing mediastinitis, pericarditis and cardiac tamponade. Patient 27 a, male, without comorbidities, denies drinking and smoking, delivery man at a food distributor. He started having an afternoon fever for 1 month, dry cough, hyporexia, sweating, weight loss and pain in the right hypochondrium. Tachycardic and feverish, pulmonary auscultation reduced in bases. Chest CT with consolidations and nodules with subpleural soft tissue density in the right lower lobe, right pleural effusion with a heterogeneous mass in the right paratracheal chain and voluminous pericardial effusion. CT abdomen with lymph node enlargement at the height of the hepatic hilum. Laboratory without leukocytosis, lymphopenia, hepatogram without alterations, normal ESR and C-reactive protein. Echocardiogram with significant pericardial effusion, signs of tamponade with diastolic restriction, inferior vena cava without variation. Drainage 750 ml of pericardial fluid and make a pleuropericardial window with biopsy. Pericardial fluid with hemorrhagic appearance, lactate dehydrogenase 689, glucose 74, proteins 5.4 g/dl, adenosine deaminase 69 g/dl, BAAR negative, cytology without cell atypia, PCR for M. tuberculosis and negative fungal culture. Serology for dengue, human immunodeficiency virus, hepatitis B and C and COVID negative. A lymph node biopsy, right paratracheal mass and parietal pleura showed a granulomatous chronic inflammatory process involving mediastinal and pleural fibroadipose connective tissue with areas of central necrosis, presence of rounded and minute structures in the necrotic central portion of the granulomas suggestive of fungal yeasts from Histoplasma sp with absence of AFB. Although the patient did not present risk factors, did not present pulmonary lesions and presented a non-specific condition, the diagnosis was suspected due to paratracheal lymph node enlargement with a granulomatous aspect, increased incidence in the state and after exclusion of common causes of tamponade. Stable discharge for outpatient follow-up. 111958 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Transient Ischemic Attack + Acute Myocardial Infarction + Pulmonary Embolism - Three Comcomitant Embolic Events in a Patient with Patent Foramen Ovale BARBARA VIDIGAL DOS SANTOS1, Lais Villela Costa Vazquez1, Rayane Fontoura Koch1, Mariane Higa Shinzato1, Maria Julia Silveira Souto1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Patent foramen ovale (PFO) is the persistence of the opening between the atrial septum primum and atrial septum secundum at the location of the fossa ovalis. It is present in about 25% of adults and is a casual finding without hemodynamic repercussions. However, studies prove an association between PFO and potentially severe clinical conditions, such as ischemic stroke, pulmonary embolism (PE), and, more rarely, acute myocardial infarction (MI). Despite well-documented consequences of paradoxical embolism through the PFO, the passage of venous clot from a patent foramen has been rarely described in the literature. We report a case of a patient with PFO and manifestation of three concomitant embolic events: venous thromboembolism, transient ischemic attack, and MI. Case Description: A 49-year-old woman with a history of idiopathic pulmonary arterial hypertension, asthma, PFO, and two previous episodes of PE sought emergency care with dyspnea on mild exertion for 2 weeks and oxygen desaturation on room air. She was admitted for compensation and clinical investigation. Chest CT angiography revealed dilatation of the pulmonary trunk and filling defects in the segmental and subsegmental arteries bilaterally. Full anticoagulation was started with enoxaparin. On the fourth day of hospitalization, the patient presented sudden burning chest pain, frontal headache, decreased consciousness, and tachypnea. ECG showed ST-segment elevation inferior MI and complete heart block, which spontaneously reverted to sinus rhythm. Patient also developed sudden left-sided hemiparesis and ipsilateral hemineglect. Non-contrast brain CT ruled out hemorrhage and aortic angiotomography excluded dissection. Due to the reported PFO, an embolic etiology was hypothesized and it was decided not to perform a coronary cineangiography and also to suspend antiplatelet drugs. The patient had complete reversal of the deficits within hours and no changes were noted in a subsequent brain CT. Cardiac magnetic resonance imaging confirmed inferior acute MI, and echocardiogram revealed PFO with small right-to-left shunt. After 18 days, the patient was discharged under oral anticoagulation and outpatient follow-up revealed no further complications. Conclusion: We report a case of paradoxical embolism manifested in distinct sites in a young patient with PFO, with good outcomes with anticoagulant therapy. 111964 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Inverted Takotsubo Cardiomiopathy in Middle Aged Man: Case Report JOAO VICTOR LIMA DANTAS 1, Hellen Dutra Passos1, Josefa Camila Menezes Reis Carvalho1, Antonio Carlos Sobral Sousa1, Joselina Luzia Meneses Oliveira2 (1) Hospital Sao Lucas - HSL; (2) Universidade Federal de Sergipe - UFS Takotsubo's cardiomyopathy is defined as a transient abnormality of left ventricular wall movement, triggered by severe emotional or physical stress, in the absence of coronary obstruction. It is estimated that the syndrome is present in 2% of all patients who come to the emergency room for suspected ACS. Multiple variants have been described, classified according to the site of involvement of the left ventricular wall. The inverted form (Inverted Takotsubo), which corresponds to basal hypokinesia/akinesia, associated with apical hyperkinesia has a prevalence of 2.2%, occupying the 3rd place among the 4 described forms, therefore, a rare condition. We report the case of a previously healthy male patient, 56 years old, hospitalized due to left tibial fracture after falling from his own height, which evolved with hemodynamic instability followed by CRP during anesthetic induction to correct the trauma. The patient was submitted to the investigation and received the diagnosis of inverted Takotsubo. Although the inverted variant is more prevalent in women and young people, the greater knowledge of the pathology has shown increased incidence in men, with physical stress being the main triggering factor. The pathophysiological process of inverted Takotsubo is similar to its typical variant and not completely understood, but there is considerable evidence that sympathetic stimulation is the central mechanism of its pathogenesis. 111970 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Scimitar Syndrome: Is the Adult Always Asymptomatic? AMANDA DE MIRANDA CONSTANTINO1, Vivian De Biase1, Beatriz Moura Sucupira Tajra1, Alana Osterno Moreira Linhares1, Mardelson Nery de Souza1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: Scimitar syndrome (CS) is a rare congenital cardiac malformation that occurs in 2/100,000 live births with a 2:1 predominance in females, it belongs to the group of partial anomalous pulmonary venous connections, which has numerous described variations, being a subtype that constitutes only 3-5% of congenital cardiac anomalies. It is classified as a heart disease with increased pulmonary and cyanogenic flow, its diagnosis is usually early, but we will highlight the importance of attention to this pathology in adult patients without a previous diagnosis. Case Report: Female patient, 39 years old, with dyspnea for 3 years, with progressive worsening of functional class. On physical examination, pulmonary auscultation was normal with 98% saturation. On cardiac auscultation, regular rhythm, with fixed split S2 and ejective systolic murmur 2+/4+ in the middle right sternal border. A chest X-ray was performed during the investigation, which showed a slightly arched tubular structure towards the right atrium with dextrocardia. In transthoracic echocardiogram evidenced anomalous pulmonary venous connections: the right pulmonary veins drain into the right atrium at the mouth of the inferior vena cava, with free flow, and the left into the left atrium. Ostium secundum interatrial communication of 13.5 mm with bidirectional flow, significant dilation of the right cavities, with right ventricular myocardium with mild hypertrophy, with preserved function. PSVD 51 mmHg and hypoplastic right pulmonary artery. Discussion: SC is a rare disease characterized by anomalous venous drainage from the lung directly into the inferior vena cava. The disease may be associated with right pulmonary hypoplasia, dextrocardia, cardiac abnormalities, and systemic pulmonary collaterals. The present case report draws attention to the late discovery of a congenital heart disease, with the patient already symptomatic and with possible important hemodynamic repercussions, highlighting the importance of always evaluating the clinical picture of dyspnea and heart failure in adults during the routine investigation. the presence of a congenital heart disease. 112001 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Role of Cardiac Magnetic Resonance in Cardiac Sarcoidosis Diagnosis YURI RHIOS ARAUJO SANTOS1, Luiz Henrique de Oliveira Bernardino1, Yuli Mendes de Souza1, Victor dos Reis Cunha1, Thaiz Ruberti Schmal1 (1) Universidade Federal de Juiz de Fora, UFJF Introduction: Sarcoidosis is an idiopathic systemic inflammatory disease marked by the formation of non-caseating granulomas, most prevalent in middle aged women and afro descendants. Diagnosis is made based on clinical, imaging, and histological findings after excluding other causes of granulomatous diseases. Although rare, Cardiac Sarcoidosis (CS) is the second cause of death in affected patients. Poor prognosis is related to ventricular dysfunction and severe arrhythmias. Although endomyocardial biopsy allows final diagnosis, guidelines using clinical and imaging criteria have been proposed to avoid invasive procedures. Case Report: A 41-year-old black woman complaining of headache develops amaurosis, hypoacusis, cutaneous lesions, dyspnea, hypotension, and tachycardia. Meningeal biopsy revealed non necrotizing granulomatous inflammation, leading to the diagnosis of neurosarcoidosis. In face of cardiac symptoms, cardiac involvement was also suspected. The electrocardiogram showed sinus tachycardia. Echocardiogram revealed moderate left ventricle (LV) systolic dysfunction, reduced Global Longitudinal Strain and hypokinesia of multiple wall segments. Magnetic Resonance Imaging exhibited mild LV global dysfunction and segmental wall dysfunction of multiple segments. Specific T2 weighted sequences showed small regions of myocardial edema and the specific sequences for late enhancement demonstrated subepicardial fibrosis of the septal apical and anterolateral basal segments and transmural fibrosis of the inferolateral medial wall as seen in the annexed image. The diagnosis of sarcoidosis with meningeal and cardiac involvement was made and imunossupressor systemic therapy was started with standard heart failure medication, leading to clinical stabilization. The patient was discharged and continued its follow-up as an outpatient. Conclusion: The current report shows that it is possible to diagnose CS in patients with a pre-established diagnosis of sarcoidosis through clinical and imaging findings. As a result, adequate treatment may be started as soon as the diagnosis is made, avoiding disease progression. 112012 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Aortic Dissection as a Manifestation of Lupic Disease Activity: Case Report RAYANNE KALINNE NEVES DANTAS1, Dieison Pedro Tomaz da Silva1, Ramon Felix de Avila1, Eduardo Caetano Abujamra1, Luciano Vaccari Grassi1 (1) Hospital de Base Sao Jose do Rio Preto; (2) Faculdade de Medicina de Sao Jose do Rio Preto Introduction: Systemic lupus erythematosus (SLE) is often associated with cardiovascular lesions, and may evolve mainly with pericarditis and myocarditis. Aortitis is a rare complication in SLE and can present itself in a variety of ways, from minimal aortic valve regurgitation to aneurysm with risk of dissection. This is an extremely rare complication, being more commonly found in patients with arterial hypertension and prolonged use of corticosteroids, and, in many cases, they are not diagnosed early and are documented during the perioperative period or by autopsy. Case Report: Female patient, 49 years old, with a previous diagnosis of systemic lupus erythematosus, systemic arterial hypertension and membranous nephropathy, using prednisone 5 mg/day, hospitalized after an outpatient consultation due to pancytopenia, arthritis and worsening of renal dysfunction, hemodynamically stable. One day after hospital admission, he developed tight chest pain, started at rest, of strong intensity and with spontaneous improvement. An electrocardiogram showed diffuse changes in ventricular repolarization and, on laboratory examination, he showed an ascending troponin curve. The possibility of lupus myocarditis was questioned and the decision was made to start pulse therapy with methylprednisolone. The patient evolved with orthopnea and jugular distension, without improvement with intense diuretic therapy, muffled heart sounds and desaturation, requiring supplemental oxygen, and was transferred to the intensive care unit. An emergency transthoracic echocardiogram was performed and confirmed the diagnosis of cardiac tamponade, probably due to lupus pericarditis. During the surgical approach for pericardiocentesis, an important acute aortic dissection was visualized. Surgical approaches for both conditions were uneventful, and today, the patient is clinically and hemodynamically stable from a cardiovascular point of view. Conclusion: Thoracic aneurysms and vascular dissections, mainly aortic, in SLE have a greater correlation with disease activity, in addition to a high risk of fatal outcome. Given this scenario, it is important to remember that aortitis is a cardiovascular manifestation in these patients, aiming for timely treatment to reduce death and disabling sequelae. 112028 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Initiating Sacubitril-Valsartan in Patient with Cardiogenic Shock in use of Inotropic Medication ANDRESSA DE MEDEIROS PULCHERIO TOSETTO1, Joana Carolina Junqueira Brum1, Vanessa Grings1, Luiz Claudio Danzmann1 (1) Hospital Sao Lucas PUCRS - HSL PUCRS; (2) Santa Casa de Misericordia de Porto Alegre Introduction: The withdrawal of inotropic drugs in patients with heart failure with reduced ejection fraction (HFrEF) is frequently challenging. In this group of patients, peripheral vasodilatation contributes for clinic and hemodynamic improvement (1). For this reason, the vasodilatory properties of neprilysin inhibitors can be of great value in this scenario. However, there's little data available in regard to the use of neprilysin inhibitors in patients receiving inotropic drugs. Case Report: A 71-year-old male patient with previous diagnosis of HFrEF with ischemic etiology (Simpson EF 31%) was admitted in a hospital in south of Brazil after cardiac arrest in a public street. The cardiac arrest rhythm was identified by first responders as ventricular fibrillation. Patient was immediately referred to coronary angiography which showed total occlusion of the circumflex coronary artery, subocclusion of the right coronary artery and severe stenosis of the anterior descending coronary artery. Performed angioplasty of the anterior descending coronary artery and intra aortic balloon and Swan-Ganz catheter insertion. Simultaneously, he needs hemodynamic support with noradrenaline, vasopressin and dobutamine. After four days of intensive care he presents hemodynamic and laboratory improvement, withdrawal of noradrenaline and vasopressin and maintenance of dobutamine at moderate doses. At this moment, sacubitril-valsartan is added to the therapeutic regimen. Initially, there were some episodes of hypotension (systolic arterial pressure 80-85 mmHg), but after 48 hours of medication was observed improvement in lactatemia and central venous oxygen saturation without hiperkalemia or worsening of renal function. In this context, it was possible to withdrawal dobutamine and discharge patient from ICU. Later, patient was discharged from the hospital with an optimized dose of sacubitril-valsartan and after 2 months, he maintained clinical stability and functional class NYHA II. Conclusion: The PIONEER-HF study (2) showed the safety of starting neprilysin inhibitors in a hospital setting, excluding patients in use of vasoactive drugs. In this case report, it was decided to start the medication in a patient while in use of an inotropic medication. This approach was taken considering data of a small retrospective analysis of 25 patients with HFrEF in use of vasodilators and/or inotropes (3). In this study, the use of neprilysin inhibitors was well tolerated and impro. 112057 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS ST-Elevation Myocardial Infarction with Two Culprit Arteries MILENA JOLY KULICZ1, Alana Ohashi1, Isadora Daleffi Zocoler1, Daniel Hideki Tashima1, Talita Beithum Ribeiro Mialski1 (1) Complexo Hospital de Clinicas UFPR (CHC-UFPR) Introduction: The ischemic heart disease is the main cause of death in Brazil and worldwide. The following case illustrates a diagnoses of ST-elevation myocardial infarction (STEMI) with two culprit arteries. Case Report: A 53-year-old man, obese and active smoker (40 pack-years), admitted at a tertiary hospital with typical chest pain for 10 hours. The admission electrocardiogram showed right bundle branch block and ST-elevation on anterior wall, DIII and aVF leads. The patient received loading doses of aspirin and clopidogrel and was referred to invasive coronary angiography, which demonstrated proximal occlusion of the right coronary artery (RCA), 99% stenosis with thrombus inside of proximal anterior descending coronary artery (LAD), and 80% stenosis of distal left coronary artery (LCA). Percutaneous coronary intervention (PCI) was performed with stent placement in the RCA and LAD. The patient was referred to the cardiac ICU requiring doses of vasoactive drugs for 24 hours, presenting significant clinical and hemodynamic improvement. After Heart Team discussion, it was performed PCI with stent placement in the LCA. The patient was discharged asymptomatic from hospital, with left ventricular ejection fraction of 39%, in addition to septal, apical, mid anterior and inferior akinesia, receiving STEMI and heart failure treatment. Discussion: Multiple Culprit Arteries are rare in STEMI and associated with worse outcomes, death and high incidence of complications, including cardiogenic shock and ventricular arrhythmias. The presented case highlights the STEMI with two culprit vessels (RCA and LAD), severe stenosis of distal LCA and good evolution after PCI. 112060 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Left Ventricular Pseudoaneurysm After Acute Myocardial Infarction: Case Report HEBER HENRIQUE ALVES LESSI1, Santiago Andres Castro Vintimilla1 (1) Instituto do Coracao Left ventricular pseudoaneurysm is a very rare complication after acute myocardial infarction, which results from ventricular wall rupture. Although rare, it can be catastrophic due to imminent risk of rupture and death. The differential diagnosis with true aneurysm is very important because it implies the patient's prognoses. We report an interesting case of presentation of left ventricular giant pseudoaneurysm after myocardial infarction in a 72-year-old man, with a history of acute coronary syndrome eighty days before he sought our service, admitted to the emergency unit with new chest pain that had started 24 hours ago. About 48 hours after admission, the patient underwent cardiac catheterization, showing multivessel disease and inferior aneurysm on cardiac ventriculography. A transthoracic echocardiogram was performed that showed an pseudoaneurysm in the basal segment of the inferior wall. The inferobasal pseudoaneurysm has a neck of 2.8 cm, a length of 4.7 cm and a distal width of 3.8 cm. Cardiac Magnetic Resonance confirmed the diagnostic in the left ventricle with increased dimensions at the expense of a giant pseudoaneurysm in the basal segment of the inferior wall and the presence of intracavitary thrombus measuring 16 x 5 mm, in the lower basal wall. The patient underwent surgical correction of the pseudoaneurysm with geometric reconstruction of the left ventricular due to free wall rupture and coronary arterial bypass grafting. A favorable hemodynamic evolution and discharge from the intensive care unit on the third postoperative day. About one week after discharge from the ICU he developed infectious complications and required readmission to the intensive care unit and died 30 days after cardiac surgery. 112066 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING Prosthetic Valve Uptake on FDG PET/CT in Absence of Endocarditis: What are the Possibilities? LEONCIO BEM SIDRIM1, Simone Cristina Soares Brandao2, Diana Patricia Lamprea1, Thais Araujo Nobrega1 (1) Pronto Socorro Cardiologico de Pernambuco - PROCAPE/UPE; (2) Hospital das Clinicas - UFPE Introduction: Positron emission tomography with 18F-fluorodeoxyglucose (FDG PET/CT) is increasingly used in cases of Prosthetic Valve Endocarditis (PVE). However, the specificity of the method still represents a limitation. It is recognized that an uptake in the perivalvular area can occur in the absence of infection. The persistence of uptake in the periprosthetic area can be explained by the persistence of a healing process around the seam ring, with endothelization. Such a process can even trigger marked fibroblast proliferation, leading to obstructive pannus in the most severe cases. Case Description: Male, 51 years old, with a history of rheumatic heart disease, with two biological aortic and mitral valve prostheses implanted 2 years ago. Admitted with paresthesia and labial commissure deviation for 3 weeks. He denied fever. Cardiac auscultation without murmurs. Cranial tomography showed hypodensity in the caudate nucleus related to the sequel of an ischemic insult. A transesophageal echocardiogram was performed, which showed a dysfunctional mitral bioprosthesis with a filamentous image measuring 3.0 cm, adhered to one of the leaflets. Blood cultures did not show bacterial or fungal growth. FDG PET/CT showed homogeneous hyperuptake in mitral and aortic perivalvular topography (maximum SUV of 5.49 and 5.28, respectively). The patient underwent surgery for valve replacement due to prosthetic dysfunction. The intraoperative finding was of vegetating lesions adhered to the prosthesis. The culture of the prosthesis was negative. Conclusion: Caution is needed when interpreting FDG PET/CT in suspected PVE, and special attention should be paid to the CVP uptake pattern and implantation time. Finally, the need to integrate FDG PET/CT results with the clinical context is highlighted. 112081 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 is the New Lupus? Chronic Pericarditis as Another Presentation of SARS-COV-2 Infection BRUNO LINHARES AZEREDO CORREA1, Jaime Lobo Figueiredo1, Sabrina Pedrosa Lima1, Fabio Akio Nishijuka1, Renata Rodrigues Teixeira de Castro1 (1) Hospital Naval Marcilio Dias Introduction: Lupus is an autoimmune disease with multiple presentations, several signs and symptoms and involvement of various organs and systems. Like Lupus, Coronavirus-19 is no longer an acute lung disease to become a multiorgan disease. The involvement of multiple systems is already well described in the literature. 2 years after the beginning of the pandemic, we are knowing its long-term effects. The cardiological spectrum has been gaining prominence after the chronification of the disease because it has a great impact on the quality of life of patients. Case Report: Female, 33 years old, no previous comorbidities, with a history of COVID-19 in April 2020 without hospitalization. Started home treatment with symptomatic and oral corticosteroids with partial improvement of symptoms. Evolving with exercise intolerance, palpitation, chest pain and symptoms of postural orthostatic tachycardia syndrome (POTs). In March 2021, after remission, she takes 2 doses of Coronavac, and returned with cardiovascular symptoms, associated of low output. She performed cardiac magnetic resonance imaging (cMRI) in April 2021 with a pattern of inflammatory injury in the pericardium. The 24-hour holter resulted sinus rhythm, sinus arrhythmias, and mean heart-rate of 104. Treated with ibuprofen for 30 days and colchicine for 6 months. In October 2021, the control cMRI showed significant improvement in pericarditis. In January 2022, a new oligosymptomatic SARS-Cov-2 infection. In March 2022 she returned with symptoms. In a new study with cMRI, the pattern of pericarditis returned. Ibuprofen was restarted for 30 days and colchicine for 6 months, maintaining medical follow-up until the present moment. Conclusion: Time has consolidated COVID-19 as another multiorgan disease. In this context, it's important to understand the pathophysiological mechanisms in the heart, generated by the long term COVID-19, as well as to develop strategies to mitigate the impacts on the functionality and quality of life of the economically active population. 112087 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Anomalous Pacemaker Lead Placement - a Report of Extrinsic Compression of the Left Pulmonary Artery AMANDA DE MIRANDA CONSTANTINO1, Vivian De Biase1, Beatriz Moura Sucupira Tajra1, Thauan Paulucio de Oliveira1, Mardelson Nery de Souza1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: The Atrioventricular Septal Defect (AVSD) corresponds to 3% of congenital heart diseases, being associated with genetic syndromes and other congenital malformations. One of the anatomical alterations present in AVSD is the posterior displacement of the atrioventricular node, located between the coronary sinus and the annulus of the atrioventricular valve, increasing the risk of injury to the same during mitral cleft repair, generating atrioventricular block (AVB), Such a complication may evolve with the need for definitive implantation of a pacemaker. Abstract: A 27-year-old female patient with complex heart disease (left atrial isomerism, partial AVSD, muscular interventricular communication, single atrium, pulmonary hypertension), underwent atrial septation surgery, mitral cleft repair and ventriculoseptoplasty in the first year of life, evolving in the postoperative period with total AVB, requiring implantation of a permanent pacemaker 1 month after the surgical procedure. In follow-up, she demonstrated heart rate reversibility, being submitted to extraction of the pacemaker generator and plasty of the abdominal pocket at age 22, remaining with the endocardial electrode. The patient evolved with symptoms of right heart failure (dyspnea, with worsening of the functional class). During the current diagnostic investigation, a significant pulmonary gradient was evidenced by the transthoracic echocardiogram, but without valvular lesion. An angiotomography of the heart and basal vessels was performed, which showed extrinsic compression of the right pulmonary artery by the pacemaker wire, which generated the pulmonary stenosis evidenced by the echocardiogram. Conclusion: Extrinsic compression by endocardial pacemaker lead is a rare phenomenon that can be difficult to recognize. In the case reported, due to the left atrial isomerism and the need to implant a permanent pacemaker during childhood in the abdominal cavity, the electrode was implanted through the azygos venous system. With the development and growth of the patient, the fixed electrode implanted in the right ventricle pulled the azygos vein under the right pulmonary artery, generating extrinsic compression and pulmonary stenosis evidenced both by imaging methods and by the patient's clinical condition. It is clear the importance of late follow-up of patients who still have implanted electrodes, even without the use of a pacemaker, in complex anatomical situations. 112084 Modality: E-Poster Young Researcher - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Pacemaker Lead Prolapse Through the Pulmonary Valve in Young Patient: Case Report MONIQUE ALMEIDA VAZ1, Gustavo Lara Moscardi1 (1) Hospital Universitario de Brasilia (HUB-UnB) Introduction: The permanent pacemakers (PPM) are most commonly implanted via an epicardial approach in pediatric patients, due to transvenous route limitations. The advent of generators and thinner leads has increased the implantation of PPM with transvenous leads over the last three decades. Growth of children causes stress on leads, which do not tolerate ongoing linear strain. Aiming to reduce conductor fractures, some redundancy should be left as slack to avoid tension, or the use of an atrial loop. However, the extra loop of lead can result in mechanical and hemodynamic complications, as lead prolapse through the pulmonary valve (PV) and its insufficiency. Case Report: A 16-year-old male with a history of congenital complete heart block, underwent dual chamber epichardical pacemaker implant on the first day of life. At age 10, transvenous atrial and ventricular leads were implanted along with pulse generator in thoracic site, left an atrial loop. During routine follow-up, he was asymptomatic and with normal average growth. Over the next year, transthoracic echocardiogram (TTE) showed prominent lead slack prolapsing across the PV, into the pulmonary artery (PA), mild tricuspid regurgitation, mild pulmonary regurgitation and normal left ventricular systolic function (56%). At age 13, TTE elucidated prolapsed lead into pulmonary valve, causing moderate regurgitation, and signs of interventricular dyssynchrony. During device interrogation, at age 16, evidence of lead fracture was found. A new TTE showed right ventricular (RV) hypertrophy and dysfunction, and redundant lead with a long loop, located inside the PA, causing double pulmonary valve lesion. Removal and replacement of the ventricular lead was indicated. Conclusion: Prolapse of transvenous lead through the PV can occur when excess slack is left for growth. The tip of ventricular lead fixated in the apex may facilitate its prolapse into PA when it is closer to the outflow tract, because of alterations in contractility and vortex flow patterns. Therefore, it is recommended to place RV leads in septal locations to avoid that complication. The treatment consists in repositioning leads, through extraction and replacement, particularly if adherent to valve apparatus. However, the pulmonary valve disfunction may be irreversible. Periodic radiographic and echocardiographic monitoring is essential in pediatric patients, allowing a preclinical detection of valvular dysfunction secondary to lead prolapse. 112120 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR IMAGING A Case of Acute Myocardial Infarction as a Complication of Atrial Myxoma JESSICA MAYARA DE FIGUEIREDO OSEAS1, Nestor Rodrigues de Oliveira Neto1, Jessione de Carvalho Lima Neto1, Matheus Fontes Leite1, Camila Albuquerque Coelho Lopes2 (1) Universidade Federal do Rio Grande do Norte, UFRN; (2) Universidade Potiguar, UnP This study aims through a case report of an unusual pathology to recall the importance of considering the importance of differential diagnosis in clinical reasoning in the care of patients with acute myocardial infarction, especially considering the possible etiologies of a type 2 infarction. A 42-year-old male patient, with no history of comorbidities, was admitted to UPA 30/02/2022 due to severe precordial pain, in sudden onset grip when performing physical exercise. Requested propaedeutics of infarction. ECG with lower wall ST segment unevenness and elevated troponin, compatible with AMI. He was referred to the university hospital for cardiac catheterization on the same day, which did not show any athertortotic lesions in coronary arteries. However, due to the abnormal vascular path observed on the examination, hemodinamycrist suggested the presence of tumor lesion in the left atrium. On 4/6, a transesophageal echocardiogram showed a mass in both atria of 6.4 x 2.6 cm, suggestive of myxoma. Surgery was performed on 4/29, and complete resection of the myxoma was performed in need of resection of the entire interatrial septum. The patient evolved clinically stable and discharged from the hospital on 05/05/2022 for outpatient follow-up with clinical treatment after AMI. This report of a type 2 infarction by an atheroembolic event due to atrial myxoma in a young patient without comorbidities exemplifies why we should not limit the diagnosis of infarctions to type 1, even if it is the most common. 112111 Modality: E-Poster Young Researcher - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Ischemic Cardiomyopathy Due to Late Diagnosis of Alcapa Syndrome AMANDA DE MIRANDA CONSTANTINO1, Vivian De Biase1, Beatriz Moura Sucupira Tajra1, Thauan Paulucio de Oliveira1, Mardelson Nery de Souza1 (1) Instituto Dante Pazzanese de Cardiologia Introduction: ALCAPA Syndrome (Anomalous Left Coronary from the Pulmonary Artery) is the anomalous origin of the left coronary artery from the pulmonary artery. Also known as Bland-White-Garland Syndrome, it is a rare congenital heart defect, present in 0.25-0.5% of patients with congenital heart defects. It can occur in isolation or be associated with other birth defects. Usually the diagnosis is early, made in the prenatal period and the need for its correction is immediate. Case Report: A 63-year-old female patient sought emergency care with chest pain, dyspnea on moderate exertion, and palpitations. Myocardial scintigraphy was positive for ischemia, corresponding to the territory of the anterior descending artery. Cardiac catheterization was requested, in which an anomalous left coronary artery was observed in the pulmonary artery trunk. The transthoracic echocardiogram showed the following findings: akinesia of the apical and anteroapical septum, with hypokinesia of the anterolateral wall and of the mid-basal segments of the anterior wall, moderate left ventricular systolic dysfunction (ejection fraction of 37%), pulmonary artery systolic pressure of 62 mmHg. It has magnetic resonance imaging of the heart, which shows the areas of infarction mentioned in the echocardiogram, without myocardial viability. Discussion: ALCAPA syndrome is difficult to diagnose, and should be suspected in children with dilated cardiomyopathy. About 85% of cases manifest up to 2 months of age, but symptoms can be misinterpreted and the disease may be underdiagnosed. The disease requires surgical treatment to restore the flow of oxygenated blood to the myocardium. The procedure of choice consists of reimplanting the coronary artery in the aorta and it is estimated that the surgical mortality is less than 5-10%, with a good prognosis after reimplantation. The peculiarity of the case reported is due to the fact that the diagnosis was extremely late and with important irreversible hemodynamic repercussions: the patient has an ischemic cardiomyopathy without myocardial viability, a condition usually related to chronic coronary artery disease or acute coronary syndromes, rarely related to ALCAPA, since due to the severity of the syndrome, its diagnosis is early. Currently, due to the lack of myocardial viability, surgical correction would not bring benefits or recovery of heart muscle, opting for clinical treatment for cardiac remodeling. 112145 Modality: E-Poster Young Researcher - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Mitral Valve in Valve Replacement Through a Bovine Pericardial Septal Patch, a Case Description of a Challenging Approach ANDRES FELIPE VALENCIA RENDON1, Marcello Augustus de Sena2, Murilo Castro3, Bernardo Kremer1 (1) Federal University of Rio de Janeiro; (2) ITPAC Palmas; (3) Palmas Medical Center 43 years old female patient, with controlled Hypertension, without any other known comorbidities. Two years ago, she was submitted to an open biological Mitral valve replacement due to severe rheumatic mitral valve stenosis. During the procedure, a highly redundant atrial septum was noted, hence an atrioseptoplasty was performed using bovine pericardium. In the recent year, she evolved with worsening dyspnea, platipnea, with a Trans Thoracic Echocardiogram showing a severe Mitral stenosis with a mean gradient of 20 mmHg. The patient declined another open-heart surgery, therefore a transcatheter approach was selected. Under general anesthesia, under guidance of Trans Esophageal Echocardiography (TEE), a Brokenbrough catheter with needle was advanced though the right femoral vein reaching the right atrial septum. Not having a clear reference of the Fossa Ovalis due to the previous atrioseptoplasty, the anatomical navigation for the septal puncture was performed under the TEE landmarks. The penetration of the bovine pericardial patch presented a high resistance with the classical approach; hence the needle was connected to an electro surgical scalpel console using 30 mV, having success at the first attempt, with no anatomical alterations or hemodynamic instability. A sapiens 3 valve was advanced to the mitral valve position with no issues after deployment, presenting a minimal atrio ventricular pressure gradient. To our knowledge, this is one of the first reports of a mitral valve in valve intervention through a previous a bovine pericardial septal patch. 112151 Modality: E-Poster Young Researcher - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of COVID-19 Infection on Post-Infectious Cardiomyocyte Compromise in a Healthy Middle-Aged Women: A Case Report GIOVANNA BOLINI BRAZAO1, Fabio Vasconcellos Brazao3, Maria Angelica Bolini Brazao2, Patricia Brazao Cohen4 (1) Centro Universitario do Estado do Para (CESUPA); (2) Universidade Federal do Para (UFPA); (3) Laboratorio Ruth Brazao, LTDA; (4) Universidade do Estado do Para (UEPA) Introduction: In the last two years, several post-infectious cardiac repercussions have been observed in SARS-CoV-2 infections. In severe cases, the infection can cause pneumonia, severe acute respiratory syndrome, cardiomyopathies, kidney failure and even death, with an impact on public health. Case Description: Female, 51 years old, without comorbidities, remained in prolonged hospitalization due to COVID-19 in a private hospital in Sao Paulo (SP). Upon admission, developed a Severe Acute Respiratory Infection, requiring admission to the ICU-Adult and later orotracheal intubation and mechanical ventilation (MV). Remained on MV for a long time and presented complications such as septic shock from ventilator-associated pneumonia, bronchitis obliterans with organizing pneumonia, which required high-dose corticosteroids, in addition to a short-term catheter-related bloodstream infection [antimicrobials used: Ceftriaxone; Cefepime; Meropenem + Vancomycin; Ceftazidime + Vancomycin; Polymyxin + Amikacin; single dose ivermectin]. At that time, presented a chest computed tomography with a report showing more than 90% of pulmonary involvement. Due to the prolonged time on MV, she needed a Tracheostomy to wean off sedatives and MV. After adequate awakening, started a process of respiratory, cognitive, muscular and sensory rehabilitation due to the critically ill patient's polyneuromyopathy. About a month after awakening, during the rehabilitation process, had an episode of chest discomfort investigated for suspected acute coronary syndrome. A transthoracic echocardiogram was performed, which showed mild hypokinesia of the anterior wall and segmental myocardial involvement of the left ventricle - non-existent changes in an exam performed one month before - in addition to the dosage of troponin (18 pg/mL) and CPK (21 U/L). The investigation and risk stratification showed no high cardiovascular risk, since they related changes to psychological stress due to the death of the patient's mother in this interval. Therefore, was released for activities and for hospital discharge. She was discharged to continue outpatient follow-up and home rehabilitation, which lasted for about 6 months. Conclusion: Studies should be carried out to accumulate more data on the cardiac repercussions of the new coronavirus and its variants in Brazil and in the world, in order to pressure public health agencies to create protocols aimed at the prevention and treatment of such cardiomyopathies. 112177 Modality: E-Poster Young Researcher - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Age of Genes: The Importance of Genetic Research in Defining the Etiology of Heart Failure BRUNO LINHARES AZEREDO CORREA1, Sabrina Pedrosa Lima1, Fabio Lucas Bassini e Silva1, Fabio Akio Nishijuka1, Renata Rodrigues Teixeira de Castro1 (1) Hospital Naval Marcilio Dias Introduction: Heart failure is not a pathology that usually affects young adults. However, once manifested, ischemic etiologies or those associated with infectious myocarditis should be ruled out. In parallel, hereditary etiologies must be considered, in which genetic tests are of enormous importance, and which are gaining more and more space in current medicine. Case Report: A 22-year-old man presented with progressive dyspnea until minimal exertion, associated with paroxysmal nocturnal dyspnea and orthopnea. Admitted with heart failure with reduced ejection fraction (EF) (admission echocardiogram EF 09% by Teichozl) hemodynamic profile B. MAGGIC Score 29 points. After the condition was compensated, triple therapy with beta-blockers, spironolactone and enalapril (ACEI) was started. Subsequently, the ACEI is replaced by the angiotensin and neprilysin receptor inhibitor (INRA) for hospital discharge. 3 weeks after discharge, she was readmitted due to decompensation associated with poor adherence to treatment. There was no water restriction. A new drug adjustment was performed, with sequential nephron block and inclusion of dapagliflozin, with a good response. During the diagnostic investigation, there was a positive family history of dilated cardiomyopathy on the part of the mother at age 25 years. Cardiac magnetic resonance imaging (cMRI) showed late enhancement with a pattern of myocardial injury of non-ischemic origin with EF 10%. Six months after admission, a new cMRI showed the same pattern, but with EF 21%, and ergospirometry with VO2max of 35.36 ml/kg/min. The genetic test showed the presence, in heterozygosity, of the variant described as NM_001458.5(FLNC):c.6976C > T;p.(Arg2326Ter), classified as pathogenic, in the FLNC gene (Filamin C), associated with Familial Restrictive Cardiomyopathy of the type 5 (OMIM:617047), of autosomal dominant inheritance. Conclusion: In young patients with heart failure, in addition to investigating the ischemic etiology or related to infectious myocarditis, one should also consider hereditary etiologies. At this point, genetic research provides important information about the definitive diagnosis and therapeutic choice. However, the high cost of genetic sequencing makes this test little available. Making it accessible will allow testing the source patient's family members and offering patient-directed therapy, ensuring improvement in symptoms and, consequently, quality of life. 112226 Modality: E-Poster Young Researcher - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Minoca in a Patient with APS After Prolonged Air Travel MILENE FERNANDES FARIAS1, Adriel Alves de Paiva; Emidio Almeida Junior Jr; Joao Marcos Bemfica Barbosa Ferreira; Katia do Nascimento Couceiro.2 (1) Fundacao Hospital do Coracao Francisca Mendes - Amazonas, Brasil.; (2) Universidade do Estado do Amazonas Introduction: Myocardial infarction without obstructive coronary atherosclerosis (MINOCA) is a syndrome with many causes, representing 10 to 15% of all diagnoses of acute myocardial infarction (AMI). Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by the plasma detection of antiphospholipid antibodies, such as anticardiolipin and lupus anticoagulant, which clinically manifests itself mainly as recurrent arterial and/or venous thrombosis. It is the main acquired cause of hypercoagulability, occurring in 2% of the general population and has high morbidity and mortality. Myocardial involvement, however, is rarely described in this pathology. Case Report: The present report describes the case of an elderly, non-sedentary, hypertensive patient, using Nebivolol 5 mg, who, after a flight to Switzerland, presented on the seventh day in that country with typical chest pain, without dyspnea, syncope or associated palpitations, electrocardiogram with millimeter elevation of V3, with flat T waves, even negative in aVL, elevated troponins, being diagnosed with acute coronary syndrome without ST-segment elevation. Echocardiogram showing normal ventricular ejection fraction (estimated at 60%), mild inferior hypokinesia. After coronary angiography, thrombosis of the posterior ventricular branches was evidenced with thrombus aspiration by microcatheter and thrombectomy with a stent retriever. Lower limb venous thrombosis was ruled out by angiographic evaluation, and treatment with low-molecular-weight heparin was initiated. Upon returning to Brazil, three months after the event, the patient was treated at a referral hospital, and a diagnostic investigation was carried out, including APS, deep vein thrombosis of the lower limbs and patent foramen ovale (PFO). Conclusion: We report the favorable outcome of primary APS with cardiological complications, which after its diagnosis determined the institution of full anticoagulation with oral anticoagulant. Clinical management of hypertension was maintained with beta-blocker therapy, with no recurrence of chest pain. Therefore, he continues to be followed up with a hematologist and cardiologist, with the aim of reducing the morbidities that may eventually exist. 112232 Modality: E-Poster Young Researcher - Case Report Category: CARDIOVASCULAR SURGERY Thrombus in the Ascending Aorta and Aortic Arch - in Association with COVID-19 ALBERT SALVIANO DOS SANTOS 1, Ana Luiza Scholl Giaretta1, Ana Maria Rocha e Pinto1, Valquiria Pelisser Campagnucci1, Camila de Queiros Mattoso Archela dos Santos1 (1) Irmandade da Santa Casa de Misericordia de Sao Paulo Introduction: Primary aortic thrombosis is a rare condition, with incidence of 0.45% in aortas with no prior lesions. It's usually presented as embolization and has a high mortality rate. Its correlation with COVID-19 was described in six cases in the literature and in our service, in three patients. Cases: The first case a 57-year-old man, a former smoker, with DM2 and thyroid cancer. Diagnosed a thrombus in the ascending aorta, received parenteral anticoagulation and after 13 days the thrombus has completely resolved. The second patient, 47 years old, smoker, hypertensive, dyslipidemic, with a history of stroke a year prior, sought medical attention for a subocclusion of the axillary artery and thrombus in the aortic arch. The patient was anticoagulated and evolved with the resolution of the thrombus. The last case, a 56-year-old female, smoker, arrived at the ER with acute myocardial infarction and acute arterial occlusion of the left upper extremity. A thrombus was found in the ascending aorta and aortic arch. The patient underwent emergency surgery. The patient progressed with biventricular dysfunction, need for an intra-aortic balloon, high doses of vasoactive drugs, and died from mixed shock and electrical instability 24 hours after surgery. Conclusion: The formation of thrombus in COVID-19 is related to endothelial inflammation due to hypoxia, increased concentration of clotting factors, and its high specificity in binding to ACE-2 receptors present in the endothelium. Primary aortic diseases are the most frequent risk factors for thrombus formation. In COVID-19-related cases, smoking was a common risk factor. Our patients had additional risk factors that, associated with the thrombogenicity of SARS-CoV-19, increased the risk of aortic thrombosis even in the absence of lesions, such as plaques or ulcers. In the surgery of the 3rd case, we observed thrombi pedunculated in smooth endothelium, without lesions. There is no consensus on treatment. Most authors advocate anticoagulation, with surgery being reserved for cases of persistence, recurrence of the thrombus or embolization. Others argue that aortotomy should be the immediate treatment to prevent complications. There is a trend toward early surgical treatment in young patients, thrombi larger than 3 cm, location in the ascending aorta or arch, recurrence of embolic events, and high thrombus mobility. 107750 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Assessment of Arterial Rigidity in Heart Transplanted Patients HENRIQUE ULISSES DUARTE DE CASTRO1, Caio Caldas Couto1, Bruno Almeida Rezende1 (1) Faculdade Ciencias Medicas de Minas Gerais (FCMMG); (2) Universidade Federal de Minas Gerais (UFMG) Introduction: Heart failure is an extremely important clinical condition whose symptoms are the result of a structural or functional disorder of the heart. Heart transplantation is a complex and high-risk procedure, but when successfully performed demonstrates a considerable improvement in the clinical condition and in the patient's quality of life. However, the vascular changes of such a procedure are not fully known. Objective: Collect and analyze data related to arterial stiffness in patients undergoing heart transplants from March 2020 to January 2021 at the Hospital das Clinicas de Belo Horizonte. Methods: The Mobil-O-Graph 24H device was used, which makes it possible to measure hemodynamic parameters of arterial rigidity that is estimated by evaluating the variables pulse wave velocity (PWV) in the brachial artery, augmentation index (AIx) adjusted for a heart rate of 75 beats per minute (Aix@75), central and peripheral arterial pressure. The measurements were made immediately before surgery and 60 days after. Results and Discussion: There was an increase in blood pressure levels after transplantation surgery for both systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure (p < 0.031). The values of central arterial pressure also increased significantly (p < 0.031). Cardiac output and cardiac index increased (p < 0.031 and p < 0.036). PWV was also increased after surgery (p < 0.031). The increase in PWV can be related to the medications used to control the rejection of the transplanted organ and hemodynamic changes. The data obtained in the study showed that there is a trend in the increase of Aix@75 after heart transplantation (which happened with all the patients studied so far). However, the inconstancy of this variable made it not possible to demonstrate that this increase was statistically significant due to the low sampling. Possibly, with the increase in the sample, it will be possible to show a significant increase in Aix@75 in the short term after heart transplantation. Conclusion: The non-invasive assessment of hemodynamic parameters can contribute to better control of the evolution of patients, in order to prevent cardiovascular events related to vascular remodeling. As it is an easily applicable method, it could be used for the continuous monitoring of the patient in different phases of the post-transplant recovery process. A longer follow-up period and a larger sample are needed to reinforce the applicability of the proposed method. 107773 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Epidemiology Profile of Patients with Infective Endocarditis in Three Tertiary Centers in Brazil LUCAS SOUSA SALGADO1, Renato Lott Bezerra2, Yago Machado da Silva3, Gustavo Guimaraes Rocha Figueiredo3, Raimundo Matos Bezerra Filho3, Eduardo Luis Guimaraes Machado3, Isabel Cristina Gomes3, Angelo Geraldo Jose Cunha1 (1) Uniao Educacional do Vale do Aco, UNIVACO, Ipatinga, MG.; (2) Hospital Joao XXIII, Belo Horizonte, MG; (3) Complexo de Saude Sao Joao de Deus, 3 Divinopolis, MG - Brazil Introduction: Infective endocarditis (IE) is a high morbimortality disease with increasing incidence. With medical improvement in diagnosis and treatment, several epidemiological changes have been reported over time, however, most of the studies were conducted in developed countries, and it is questionable whether developing countries are susceptible to this epidemiological transition. Objectives: It was sought to describe the epidemiological profile, mortality predictors, and analysis of possible microbiological transition from patients admitted to three tertiary centers in Brazil. Methods: In this cross-sectional and retrospective study, data from 211 patients with definite or probable IE were analyzed according to the modified Duke criteria, between 2003 and 2017. The association between categorical variables was assessed using Chi-square or Fisher's exact test and binary logistic models were built to investigate the death outcome. We considered p < 0.05 as statistically significant. Results: Median age of the sample was 48.00 (33-59) years old, 70.6% were men and the most prevalent pathogen was Staphylococcus spp. (19%). Mortality was 22.3% and it was observed that increasing age is the leading risk factor for death (p = 0.028). With regard to the location of the disease, native valves were the most affected, with aortic valve being more affected in men when compared to women (p = 0.017). The average number of cases of Staphylococcus spp. (t = 0.293, p = 0.148) and Streptococcus spp. (t = -0.078, p = 0.727) has remained stable over the years. Conclusion: No trend towards a reduction or increase in mortality between 2003 and 2017 was evident. Although Staphylococcus spp. was the most prevalent pathogen, it was not possible to observe the expected epidemiological transition. 107794 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Predictors of Late Extubation from Mechanical Ventilation After Cardiac Surgery Maria Luisa Souza Santana1, Rodrigo Carvalho de Menezes2, Isabella Bonifacio Brige Ferreira3, Kaique Vinicius da Cruz Santos Aguiar4, Raissa Barreto Lima3, Ana Luisa de Aguiar Almeida Silva5, Elias Soares Roseira5, Luiz Carlos Santana Passos6, Rodrigo Morel Vieira de Melo6, Nivaldo Menezes Filgueiras Filho1 (1) Medicine, Salvador University, C ampus Teacher Barros, Salvador, Brazil; (2) Human pathology, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (3) Medicina e saude, Bahia School of Medicine and Public Health - C abula, Salvador, Brazil; (4) Gemini, Grupo de Estudos em Medicina Intensiva, Salvador, Brazil; (5) Medicine, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (6) Medical board, Hospital Ana Nery, Salvador, Brazil Introduction: Prolonged use of mechanical ventilation has been associated with poor clinical outcomes, and about 10% of patients who undergo heart surgery are part of this group. Identifying those who are at a higher risk for late weaning may assist in the management of these patients, decreasing the risk of death and complications. Objectives: To determine factors associated with late extubation (>6 hours) after cardiac surgery. Methods: Retrospective cohort study, with secondary data analysis from Ana Nery Hospital's, Bahia, Brazil, patients who underwent cardiac surgery between 2018 and 2021. The D'agostino test was used to assess normality. Continuous variables were assessed using the Mann-Whitney test, categorical variables using Fisher's exact test. Variables that showed statistical relevance in the univariate analysis were included in a binary logistic regression model. Results: A total of 1594 patients were admitted to the study, with a mean age of 56 years (45-66) and a slight predominance of male patients. The most performed surgery was coronary artery bypass grafting (635 [40.1%]). Median Society of Thoracic Surgeons (STS) score of 1.17 (0.70-2.08) and a EUROscore of 1.30 (0.86-2.15). Among admitted patients, 860 had late extubation (>6 hours) MV, with a median of 12 (9-18) hours on the machine while patients who had early extubation had a median of 4 (2.5-5) hours on MV. 74.2% had type 2 diabetes. They also had more noradrenaline use - 55.3% - less vasopressin use (6.86%), with a median peak troponin of 3.51 (1.67-8.24). Conclusions: The presence of congenital valvulopathy, history of endocarditis, troponin and lactate values, presence of previous type 2 diabetes, and use of vasopressin and debutamine were independently associated with late extubation. 107813 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Predictors of Intra-ICU Complications After Cardiac Surgery ANA CAROLINA RIOS CARVALHO1, Maria Luisa Souza Santana1, Rodrigo Carvalho de Menezes2, Isabella Bonifacio Brige Ferreira3, Kaique Vinicius da Cruz Santos Aguiar4, Raissa Barreto Lima3, Ana Luisa de Aguiar Almeida Silva5, Elias Soares Roseira5, Luiz Carlos Santana Passos6, Rodrigo Morel Vieira de Melo6, Nivaldo Menezes Filgueiras Filho1 (1) Medicine, Salvador University, C ampus Teacher Barros, Salvador, Brazil; (2) Human pathology, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (3) Medicina e saude, Bahia School of Medicine and Public Health - C abula, Salvador, Brazil; (4) Gemini, Grupo de Estudos em Medicina Intensiva, Salvador, Brazil; (5) Medicine, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (6) Medical board, Hospital Ana Nery, Salvador, Brazil Introduction: Cardiac surgery aims to restore the functional capacity of the heart and reduce symptoms. Complications have a negative and variable effect on outcome after cardiac surgery. Therefore, the measurement of its effect is of fundamental importance. Objectives: To determine patient characteristics associated with complications post-cardiac surgery. Methods: Retrospective cohort study, with data analysis from Hospital Ana Nery's, Bahia, Brazil patients who underwent cardiac surgery between 2018 and 2021. The D'agostino test was used to assess normality. Continuous variables were evaluated using the Mann-Whitney test, and categorical variables evaluated using Fisher's exact test. Variables that showed statistical relevance in the univariate analysis were included in a binary logistic regression model. Results: A total of 1594 patients were admitted to the study, with a mean age of 56 years (45-66) and a lower predominance of male patients. The most performed surgery was coronary artery bypass grafting (635 [40.1%]). The study population has a median Society of Thoracic Surgeons (STS) score of 1.17 (0.70-2.08) and a EUROscore of 1.30 (0.86-2.15). 279 patients had intra-ICU complications. These were older (58 [48-67] vs. 56 [45-65]), median 85 (64-110) min on cardiopulmonary bypass, 62.2% used dobutamine, 64.4% used noradrenaline. Among complications, 183 (65.6%) had infection, 103 (37.3%) required reoperation, 56 (20.1%) had acute kidney injury, 11 (9.73%) had stroke, and 23 (8.30%) required dialysis. Conclusions: Cardiopulmonary by-pass time, debutamine use, presence of type 2 diabetes, chronic kidney disease, and use of intra-aortic balloon pumps were identified as independent risk factors for the development of postsurgical complications. 107814 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Mortality Predictors After Cardiac Surgery ANA CAROLINA RIOS CARVALHO1, Maria Luisa Souza Santana1, Rodrigo Carvalho de Menezes2, Isabella Bonifacio Brige Ferreira3, Kaique Vinicius da Cruz Santos Aguiar4, Raissa Barreto Lima3, Ana Luisa de Aguiar Almeida Silva5, Elias Soares Roseira5, Luiz Carlos Santana Passos6, Rodrigo Morel Vieira de Melo6, Nivaldo Menezes Filgueiras Filho1 (1) Medicine, Salvador University, C ampus Teacher Barros, Salvador, Brazil; (2) Human pathology, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (3) Medicina e saude, Bahia School of Medicine and Public Health - C abula, Salvador, Brazil; (4) Gemini, Grupo de Estudos em Medicina Intensiva, Salvador, Brazil; (5) Medicine, Federal University of Bahia Ondina C ampus, Salvador, Brazil; (6) Medical board, Hospital Ana Nery, Salvador, Brazil Introduction: Risk prediction models have been developed to provide information about risk for both physicians and patients, as well as to guide decision making. Likewise, knowing a patient's risk may allow the implementation of individualized strategies, aimed at preventing mortality. Objectives: To determine patient characteristics associated with post-cardiac surgery Mortality. Methods: Retrospective cohort study, with secondary data analysis from Ana Nery Hospital's, Bahia, Brazil, patients who underwent cardiac surgery between 2018 and 2021. The D'agostino test was used to assess normality. Continuous variables were evaluated using the Mann-Whitney test, and categorical variables evaluated using Fisher's exact test. Variables that showed statistical relevance in the univariate analysis were included in a binary logistic regression model. Results: A total of 1594 patients were admitted to the study, with a median age of 56 years (45-66) and a lower predominance of male patients [RCdM1] [MS2] The most performed surgery was coronary artery bypass grafting (635 [40.1%]). The study population has a mean Society of Thoracic Surgeons (STS) score of 1.17 (0.70-2.08) and a EUROscore of 1.30 (0.86-2.15). Among the patients who did not survive, it was observed that a median age of 66 (53.3-71), BMI with a median index of 24.4 (21.5-27.6), higher rate of CKD and 41.6% had previous AMI. They had a higher EUROscore - 2.58 (1.45-3.76) - and STS - 2.05 (1.31-3.75), needed more supportive medications, and had more postoperative complications, measuring up to 51.1%. Conclusions: BMI, peak 24-hour lactate, CKD, presence of complications in the intensive care unit, use of norepinephrine and vasopressors were identified as risk factors associated with postoperative patient mortality. 107822 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Echocardiographic Evaluation of Secondary Cardiotoxicity in Women's Breast Cancer Treatment IVANA BECKER1, Bruna Strube Lima1, Joao Pedro Dutra2, Samantha Cristiane Lopes1, Susane Fanton3, Franciani Rodrigues da Rocha1, Marcelo Vier Gambetta1, Luiz Eduardo Bacca1, Caroline de Oliveira Fischer Bacca1 (1) UNIDAVI - Centro Universitario para o Desenvolvimento do Alto Vale do Itajai; (2) CEPON - Centro de Pesquisas Oncologicas; (3) FURB - Universidade Regional de Blumenau Background: The introduction of new chemotherapy drugs has improved overall survival for patients fighting breast cancer. They might however be the cause of secondary structural or functional alterations to the heart, defined as cardiotoxicity. Objectives: To identify the incidence of secondary cardiotoxicity in breast cancer treatment while emphasizing its demographical, clinical, and echocardiographic characteristics. Methods: Observational, analytical, and cross-sectional study in the oncology sector of a reference hospital in Alto Vale do Itajai, Santa Catarina, Brazil. We analyzed 238 patient's records of women under medical echocardiographic supervision from August/2018 until June/2021. It was defined as cardiotoxicity the presence of left ventricular dysfunction, represented by the reduction of at least 10% in the ejection fraction (LVEF) to values of lower limits of normality (LVEF <50%). It was employed the SPSS software, Kolmogorov-Smirnov normality, and Fisher exact tests. The chosen level of significance was p < 0.05. Results: The sample counted on 118 women who met eligibility criteria. Average age was 52.73 +- 12.35 years. The incidence of cardiotoxicity was 2.5% (4 patients), meaning significance to the association between treatment with trastuzumab and radiotherapy (p < 0.05). There wasn't any statistical relevance in the analysis of sociodemographic parameters, as well as in the clinical data related to CT outcomes. Conclusion: The incidence of cardiotoxicity in women under medical echocardiographic supervision during breast cancer treatment was 2.5%, with statistical relevance to the association between treatment with trastuzumab and radiotherapy. 107900 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY An Evaluation of the Recommendations for the Blood Pressure Measurement in Patients who Underwent Mastectomy JULIA DE CONTI PELANDA1, Andre Vinicius de Oliveira1, Annelise de Jesus Oliveira1, Mateus Rodrigues Alessi2, Alexandre Alessi1 (1) Universidade Federal do Parana (UFPR); (2) Universidade Positivo Introduction: Patients who underwent mastectomy as cancer treatment are often advised not to measure their blood pressure (BP) in the ipsilateral arm and to avoid many daily-life activities, in order to prevent lymphedema. These recommendations are based on a small number of studies with widely controversial results. Hence, a thorough review of the literature is imperative to better evaluate the adequacy of the current guidelines. Methods: A cross-sectional online survey with cardiologists and mastologists, and a semi-systematic literature review were performed. Data were cross-linked to assess the degree of concordance between clinical practice and guidelines. Survey results were evaluated by Chi-Square test, with a significance level of 95%. Results: From the 334 physicians surveyed, 206 (62%) were mastologists and 128 (28%) were cardiologist. Whereas cardiologists contraindicated measuring the BP after mastectomy (Chi2 20.1, p < 0.001), sentinel lymph node biopsy (Chi2 25.6, p < 0.001) and radiotherapy (Chi2 18.5, p < 0.001), mastologists did not. According to the literature, there is no data supporting the maleficence of such procedure in mastectomy patients. Conclusion: These results highlight the discrepancy of recommendations among physicians of different specialties, which can increase patients' illness anxiety. In this study, mastologists showed greater awareness of risks and benefits of measuring the BP in the ipsilateral arm of the procedure. 107945 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Risk Reclassification by Subclinical Atherosclerotic Disease in the Brazilian Diabetes Study SOFIA HELENA VITTE1, Joaquim Barreto1, Andrei C. Sposito1 (1) Universidade Estadual de Campinas Background: Cardiovascular risk estimates assist healthcare providers in targeted selection of type 2 diabetes (T2D) individuals who may benefit the most from stricter control of risk factors. Subclinical cardiovascular disease (SCD) either as carotid plaque or coronary calcifications is a surrogate marker of increased incidence of cardiovascular events and is thus employed as a classifying feature. Whether screening SCD significantly reclassifies the estimated risk of T2D individuals assessed by risk engine equations at the primary prevention level remains unexplored. Objectives: We sought to determine whether SCD significantly reclassified the UKPDS-based risk estimates in T2D individuals at primary prevention. Methods: This is a cross-sectional study with data collected by the national prospective cohort Brazilian Diabetes Study. Briefly, in this cohort, patients with DM2, aged >=30 years, underwent carotid Doppler ultrasound for common carotid intima-media thickness (CIMT) measurement and computed tomography angiography to calculate coronary calcium score (CAC). SCD was considered in those who had at least one of the following: (i) carotid atherosclerotic plaque; (ii) CIMT > percentile 75; (iii) CAC > 0 Agatston. The UKPDS risk engine was used to estimate the 10-year risk of CV events classified as low (<15%), intermediate (15-30%) and high-risk (30%). Receiver operator curve (ROC) was used to evaluate the predictive value of UKPDS value. The proportion of individuals at each risk class were compared between the UKPDS and the UKPDS + SCD groups by chi-square test. Results: Among 371 patients included in this analysis (Mean age: 58 + 7.5 years; T2DM duration: 9 + 6.7 years; 59.8% male), 302 (81.4%) had SCD defined by either CIMT (72.4%) or CAC score (71.6%). The UKPDS had an area under the curve of 0.66 (95%CI: 0.60, 0.74; p < 0.001). Adding SCD data to the UKDPS risk engine significantly change the proportion of individuals classified as low- (80.32% vs 17.25%), intermediate (15.36% vs 1.08%) and high-risk (4.31% vs 81.67%) (p < 0.001 for all). Only 5% of SCD individuals were classified as high-risk by UKPDS. 108555 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Aspects and Number of People Affected by Malignant Neoplasm of the Heart, Mediastinum and Pleura in Brazil from 2019 to 2021 AUREA NATHALLIA GOMES DE SOUZA1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa UNIFAP Introduction: Malignant Neoplasm of the Heart, Mediastinum and Pleura (MNHMP) is considered a rare condition, which could only be better studied after improving diagnostic methods. Heart tumors originate mainly in internal tissues, such as the muscular layer and the pericardium, presenting with symptoms common to other cardiovascular diseases, requiring a differential diagnosis. Objective: To analyze the epidemiological aspects and number of people affected by MNHMP, in the years 2019, 2020 and 2021, observing the variation of numbers over the years and main epidemiological findings. Methods: We used the data available in the PAINEL-ONCOLOGIA, from the Department of Informatics of the Unified Health System (DATA-SUS), which comes from the Outpatient Information System (SIA). Results: It was observed, a reduction in the number of cases of people diagnosed with MNHMP over the years. In 2019, 1420 cases were recorded, in 2020, there were 1273 and in 2021, the decrease was more pronounced, totaling 621 cases. Concerning gender, it was found that the frequency in females is slightly bigger, in 2019, 50.53% were females, in 2020, they corresponded to 53.18% of cases and in 2021, they represented 52.17%. Furthermore, another important epidemiological aspect is the age group of these patients, where it was possible to observe that in 2019, in the age group from 0-19 there were 103 cases, and a larger group, which comprises 45-79 years old, represents 58.87% of the cases that year, where those aged 65-69 reached 178 cases. In 2020, the age group from 50-74 years old stood out, with greater attention to 55-59 years old, with 180 cases. In 2021, with the decrease in the total number, no age group exceeded 100 cases, with the highest number, 77 cases, patients between 60 and 64 years old. It was also possible to analyze the distribution of these cases throughout Brazilian territory, some states maintained higher numbers of MNHMP diagnoses during the analyzed period: Bahia, Minas Gerais, Rio de Janeiro, Sao Paulo and Rio Grande do Sul. Conclusions: It is possible to sketch epidemiologically, from the data, that MNHMP affects more females than male, from the fifth decade of life, who live mainly in the states of Bahia, Minas Gerais, Rio de Janeiro, Sao Paulo and Rio Grande do Sul. It is necessary to pay attention to the sudden decrease that occurred from 2020 to 2021 and not rule out the possibility of underreporting, mainly because of the current pandemic. 108595 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Mortality Due to Essential Hypertension in the Northeast Compared to Brazil and Schooling LARISSA DE OLIVEIRA BELTRAO1, Ricardo Henrique Freitas Tavares2, Maria Keyllane Vasconcelos de Miranda2, Isabella Carla Barbosa Lima Angelo2, Ieda Fernanda da Silva Santos2, Henrique Pessoa Tseng2, Joao Henrique Neves Ferreira2, Carlos Henrique Pereira da Silva2, Matheus Guilherme de Assuncao Franca2, Maria Luisa Lopes Rodrigues2, Erinaldo Siqueira de Medeiros2, Pedro Rafael Salerno2 (1) Faculdade Pernambucana de Saude (FPS); (2) Universidade Catolica de Pernambuco (UNICAP) Introduction: Systemic Arterial Hypertension (SAH) is a chronic and non-communicable disease of multifactorial origin, characterized by sustained elevation of systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg, when it has no clearly identifiable cause, it is called essential hypertension. It was estimated that almost a quarter of the Brazilian population has hypertension. Objectives: This study aims to compare the mortality rate from essential hypertension and relate it to years of study between the Northeast Region and Brazil. Results: It was observed that there were 241,797 deaths resulting from essential hypertension in Brazil from 2010 to 2019, with 78,134 cases in the Northeast region, characterizing it as the second region with the most deaths due to this pathology, representing 32.31%. In addition, regarding education, in individuals who had no years of study, there were 33,641 deaths in the Northeast, representing a rate of 51.31%. Furthermore, among patients with 1 to 3 years of study in the Northeast, there were 16,062 deaths, with 26.42% of the total in Brazil. As for the population with 4 to 7 years of study, 8,049 deaths were obtained in the Northeast, representing 20.44%. In relation to 8 to 11 years of study, 3,704 deaths were recorded in the Northeast, constituting 19.61%. In addition, in individuals with 12 or more years of study, the Northeast represented a total of 906 deaths, with 16.17% of the total. Finally, in some notifications, the degree of education was not reported, which represented 15,772 deaths in the Northeast, representing 30.57%. Conclusion: The schooling factor is a variable to be considered when assessing death from SAH, highlighting the Northeast region of Brazil. It was observed that mortality rate was inversely proportional to the level of education, with half of the national cases occurring in individuals who did not have training, demonstrating the relevance of this variable. Thus, health prevention and promotion measures are needed for patients with low schooling to control essential hypertension in order to reduce complications resulting from this disease. 107996 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Outcomes of Palliative Care Interventions in Patients with Heart Failure: A Systematic Review of the Literature HITESH BABANI 1, Hitesh Babani1, Giovana De Oliveira Sarubi1, Marjorie Binda Leite1, Guilherme Henrique Souza1, Rania Gabriele Said1, Ornella Aquino Da Silva1, Lorrana de Oliveira Teixeira1, Adria Melissa Silva Campos1, Jessica Alessandra Cruz Dos Santos1, Rodrigo de Souza Leitao2 (1) Centro Universitario Fametro; (2) Fundacao Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Background: Heart failure (HF) is a progressive life-limiting condition affecting 1-2% of the general adult population in high-income countries. By 2030, it is estimated to affect 8 million people, consuming more than $69 billion in medical costs. Patients with advanced HF have a risk of premature death and report physical symptoms, psychosocial burdens, and spiritual needs, making necessary the interventions of PC (palliative care). PC offers total care for a person with an incurable disease which may still respond to disease-modifying treatments, but is nonetheless progressive and life-shortening and is not limited to a specific diagnosis, nor to a particular prognosis. Aims: This document aims to identify outcomes of PC intervention in patients with HF and ascertain the efficacy of management. Methods: A systematic literature review was developed in three steps: Development of the research question, search for scientific articles in the Pubmed database and critical analysis of included articles. The search was conducted in March 2021, and articles between 2019 and 2022 were selected, for a total of 74 articles, of which 19 were used. Results: PC interventions improved quality of life, symptom burden, physical symptoms, mental symptoms, and patients were able to end their life with dignity. The PC needs to be based on multidisciplinary team management for end-stage HF with the purpose of improving quality of life and reducing healthcare costs. In addition, the presence of a multidisciplinary team was associated with multiple positive results. The outcomes of improving access to palliative care for people with advanced HF might reduce their suffering and of their loved ones, as well as decrease hospital readmissions. Conclusions: PC aims at integral care and approaches the patient as a whole (spiritually, socially, physically, and emotionally) these interventions should be provided alongside optimal cardiologic management. This study indicates that there are associations between PC and positive outcomes for patients with end-stage heart failure, resulting in a substantial improvement in quality of life as well as comfort and dignity whilst dying. 108575 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Trisomy 21 and Congenital Heart Defects: Frequency and Types Verified in a Sample of 299 Patients ISADORA BUELONI GHIORZI1, Mauricio Rouvel Nunes1, Mateus dos Santos Taiarol1, Marina da Rocha Besson1, Eliaquim Beck Fernandes1, Adriano Louro Moreira1, Juliana Bergmann1, Giulia Righetti Tuppini Vargas1, Konopka1, Valberto Sanha1, Thais Vanessa Salvador1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre Introduction: Patients with trisomy 21, or Down syndrome (DS), have an increased risk of presenting congenital heart defects (CHDs). They have been described in around 40-50% of the patients. Objective: To detect the frequency and types of CHDs in a sample of patients with DS. Methods: The sample was composed by patients seen at a Genetics Clinic Department, in a period between 1994 and 2008. Data was collected retrospectively, emphasizing the cardiological assessment. All patients underwent cytogenetic evaluation through GTG-Banding karyotype. Results: Among the 299 patients from the sample, 166 (55.5%) were male. The mean age at first evaluation was 23.4 days. The predominant karyotypic abnormality was trisomy 21 (96%). Structural abnormalities were found in 3% of patients of the sample, and mosaicism was found in 1% of them. Two hundred and thirty two patients (77.6%) underwent cardiological assessment, and 160 of them (69%) presented abnormal physical examination findings. Among them, 151 underwent echocardiography, and malformations were detected in all of the patients. Among the 72 patients with normal findings (31%), 41 underwent echocardiography, and malformations were detected in 3. Therefore, CHDs were detected in 154 patients among the 232 who underwent cardiological assessment (66%). The most common CHDs observed were: atrioventricular septal defect (n = 61; 39.6%), atrial septal defect (n = 60; 39%), ventricular septal defect (n = 38; 24.7%), and patent ductus arteriosus (n = 38; 24,7%). Other CHDs consisted of Fallot tetralogy (n = 12; 7.8%), pulmonary stenosis (n = 7; 4.5%), pulmonary atresia (n = 1; 0.65%), and Ebstein abnormality (n = 1; 0.65%). Conclusions: Data of this study confirm the increased prevalence of CHD in patients with DS. Therefore, as opposed to what was observed in this sample, in which 22.4% were not assessed, this study reinforces the importance of cardiological assessment in every child with DS, since it may have a significant impact on their prognosis. 108730 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Effects of Strengthening the Surae Triceps Muscle on Venous Pump Function in Chronic Venous Insufficiency LUISA PEREIRA DE OLIVEIRA ZANETTI GOMES1, Ana Carla Schmidt1, Camila Martins Marinelli1, Ricardo Zanetti Gomes1 (1) Universidade estadual de ponta grossa; (2) Universidade da regiao de Joinville Chronic venous insufficiency (CVI) is a common disease that causes calf muscle pump dysfunction and has repercussions for the hemodynamics of the structures involved. To analyze the effects on venous hemodynamics of exercises to strengthen the calf muscles in patients with CVI. This non-randomized clinical trial analyzed 25 lower limbs with CVI, classified from C1 to C5 according to CEAP, Were included if they had achieved at least 60% attendance in the calf strengthening group session. The variables analyzed were collected at at baseline, after 1 month and 2 months and at the end of the exercise protocol. The isometric dynamometry, goniometry, leg circumference and adipometry of the calf The intervention duration 24 session. Both open and closed kinetic chain exercises were performed, involving plantar and dorsal flexion of the ankle joint. Initially, a descriptive analysis of patient variables was conducted, estimating simple frequencies. The variables were analyzed with estimation of mean, median, standard deviation, and 25th and 75th percentiles for each data collection period. Differences between different data collection times were tested with the Friedman test followed Bonferroni correction. In this study were included 25 limbs, comprised of women, who had been diagnosed with CVI for a mean of 6.4. The results of the comparison between the first and the last section showed that there was an increase in the muscular strength of 0.5 kgf (p = 0,2) In the dorsiflexion and plantar flexion measurements increase by 5o (p < 0,0001). The leg circumference increases 0,6 cm (p = 0,215). The Adipometry reduce in 5 mm (p < 0.001). At the analysis of the dynamometry results, there were no statistically significant. The dorsiflexion and plantar flexion there was an increase of 5o at the C3 in the dorsiflexion, at the C2 group in the plantar flexion (p < 0,002). The leg circumference increase 1,2 cm in the group C1 (p = 0.045). The adipometry results showed a reduction at the C3 classification of 1 mm (p = 0,004), Administration of exercise protocols should be considered as a treatment option for CVI, since it has a positive impact on risk factors and on the functions that are impaired by this pathology. A positive impact was observed after the 3 month at the muscular strength, adipometry, range of movement in the patients. 108010 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY "Study of the Role of Focal Adhesion Kinase in the DNA Damage Response in Cardiomyocytes Exposed to Doxorubicin by Super-Resolution Structured Microscopy" ANTONIO DOSUALDO NETO1, Aline Mara dos Santos2, Ana Paula Samogim2, Isabela Aparecida Moretto2, Gabriel Macherini Quaglia2, Andre Alexandre de Thomaz2 (1) Pontificia Universidade Catolica de Campinas (PUC-CAMPINAS); (2) Universidade Estadual de Campinas (UNICAMP) Introduction: Cardiovascular complications of anticancer therapies are emerging as a major public health problem, considering that the cancer survival rate has increased considerably in recent years. Cardiotoxicity resulting from the action of chemotherapeutic agents, such as Doxorubicin (doxo), is a serious condition that can progress to chronic cardiomyopathy, congestive heart failure and patient death. Studies focusing on signaling activated by antineoplastic therapies have demonstrated the importance of focal adhesion kinase (FAK) for cell survival and resistance to this treatment, however, this signaling remains poorly understood. The present work aimed to characterize the effects of treatment with the chemotherapy drug doxo on the subcellular redistribution of FAK in H9C2 cardiac myocytes. Furthermore, we investigated the interaction between FAK and DNA damage response (DDR) related proteins after doxo treatment, such as DDX5, XRCC5 and DNA-PK which were previously identified in FAK co-immunoprecipitation experiments. Objective: Investigate whether FAK is modulated by Doxo in cardiac myocytes and whether this protein co-localizes with DNA damage response (DDR) proteins by means of super-resolution microscopy. Methodology: Culture of ventricular cardiomyoblasts (n = 80 cells), treatment with doxorubicin, immunostaining of proteins with subsequent analysis by Super Resolution Microscopy were performed. Finally, the T-Student distribution was used for the statistical data and the comparative effect between the control and chemotherapy groups was detailed by the ImageJ program. Results: Among the main findings, it was found that there is an accumulation of activated FAK in the nucleus and the approximation between this kinase and the DDR proteins during genotoxic stress by doxo, indicative of mutual action to maintain cell viability. Furthermore, doxo stress did not cause a significant gain in fluorescence intensity of DDX5, but a subnuclear redistribution accompanied by FAK. XRCC5 and DNA-PK increased their intensities in cells treated with chemotherapy, with concomitant approximation of FAK. Conclusion: The findings of this project contributed to the understanding of the mechanisms by which FAK promotes cell survival against treatment with doxo and, in addition, may contribute to the establishment of new therapeutic modalities for tumor treatment with reduction of the deleterious effects on cardiac function. of the patient. 108048 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Orthostatic Hypotension is Related to Subclinical Coronary Artery Disease in Type 2 Diabetes Individuals ANA RAQUEL WHITAKER FILIPE1, Ana Raquel Whitaker Filipe1, Sofia Helena Vitte1, Daniel Campos de Jesus1, Joaquim Barreto1, Andrei C. Sposito1 (1) Universidade Estadual de Campinas (UNICAMP) Introduction: Orthostatic hypotension (OH) is a surrogate marker of poor prognosis in type 2 diabetes (T2D) and results at least partially from arteriosclerosis, autonomic dysfunction, and glucotoxicity; all features involved also in the progression of atherosclerotic cardiovascular disease. Objective: To determine whether OH is related to subclinical coronary artery disease (SCD) in T2D individuals. Methods: This was a cross-sectional, predefined analysis of the Brazilian Diabetes Study, a single-center, prospective cohort of T2D. After 3-min resting sited with their arms at their heart level, participants had their blood pressure (BP) measured three times with a 1-min interval between each measurement and the mean value of the last 2 was considered. Orthostatic BP was then measured as the BP obtained after 1-min standing. OH was defined as an orthostatic systolic or diastolic BP drop greater than 20 mmHg and 10 mmH, respectively, when compared to sitting BP. SCD was a coronary calcium score above zero in individuals without prior acute coronary syndrome, coronary revascularization, or stable angina. Logistic regression was used to evaluate the influence of the independent variable, OH, on the dependent variable, SCD, and further adjustment by age, gender, and LDL-C was performed. To assess if OH was related to SCD severity, ordinal logistic regression was performed using OH as a predictor of higher CAC groups (0, 1-99 and > 100 Agatston). Results: Among 366 individuals (mean age, 57 + 8 years; 58% male; T2D duration, 9 years), included in this analysis, 41 (11.2%) had OH and 260 (71%) had SCD. Compared with controls, HO group were older (57 + 7.4 vs 60 + 7.8 years; p = 0.034), had higher levels of LDL-C (106 + 38 vs 121 + 40.1, p = 0.033) and displayed a higher prevalence of SCD (69.2% vs 85.4%, p = 0.032). HO was related to SCD with an OR of 2.59 (95%CI: 1.06, 6.36; p = 0.037), which remained significant after adjustment (OR: 2.87; 95%CI: 1.03, 8.03, p = 0.044). OH was significantly related to the chance of being classified at a higher CAC group in logistic ordinal regression, with an OR of 2.34 (95%CI: 1.09, 5.01, p < 0.001). Conclusion: T2D individuals with HO are at an increased risk of SCD. This should be borne in mind of healthcare providers when assessing CV risk in this population. 108065 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risks of Hormone Replacement Therapy in Transgender Women: A Systematic Review PRISCILA PEREIRA ALBUQUERQUE1, Kassielly Melissa Ribeiro Rodrigues1, Nathalia Bianco Fabris1, Rodrigo Lage Carneiro1, Joao Gabriel Pacetti Capobianco1 (1) Pontificia Universidade Catolica de Minas Gerais campus Pocos de Caldas Introduction: There is a growing number of transgender women who use hormone replacement therapy (HRT), based mainly on the use of estrogen, so it's necessary to understand their effects on the individual's health. The main goal of this treatment is to adjust secondary sexual characteristics to be congruent with your gender. The impact of hormone therapy on cardiovascular health is not widely known. Objective: The study aims to perform a systematic review on what are the cardiovascular risks caused by hormone therapy in transgender women. Methodology: The search was performed using the following electronic databases: Pubmed, Scopus, BVS, Scielo, Web Of Science, Science Direct, Sage Journals, DOAJ, Oxford Journal, Lippincott Williams & Wilkins Journals from 2015 to 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology using the terms "Hormone treatment AND Transgender AND Cardiovascular diseases". Only primary studies were included, which investigated the cardiovascular effects of HRT in transgender women. Reviews, meta-analyses, non-primary studies, animal studies, and adolescent studies were not included. Results: Of the 228 articles found, after applying the inclusion criteria, 7 articles were selected for analysis. The results were heterogeneous and showed that cross-sex hormone therapy impacts the health of transgender women in several aspects, such as: changes in blood pressure (BP), lipid profile, body mass index (BMI) and vascular compromise. Regarding BP, 2 studies showed an increase in blood pressure levels and 1 observed reduction. As for changes in the lipid profile, 2 studies didn't observe changes, however, 2 other studies reported a decrease in these parameters. Only 1 study showed an increase in BMI as a consequence of the use of HRT. Concerning, vascular compromise, 1 study reported the occurrence of deep vein thrombosis, on the other hand, another study with 676 transgender women showed only one case. Conclusion: The heterogeneity of the results found in relation to the effects of HRT indicates the need for studies with larger samples that longitudinally follow up individuals involved in this process. The recent beginning of the use of this therapy and the neglect that this population group suffers from society are the factors identified by the authors as responsible for the lack of robust data regarding the safety of HRT for the health of transgender women. 108066 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Diabetic Polyneuropathy is Related to Carotid Artery Disease in Type 2 Diabetes Individuals NATALIA CHICANI ZORZETO 1, Sofia Helena Vitte1, Daniel Campos de Jesus1, Ana Raquel Whitacker Filipe1, Joaquim Barreto1, Andrei Carvalho Sposito1 (1) Universidade Estadual de Campinas - UNICAMP Introduction: Sensory-motor diabetic polyneuropathy (DP) is driven by axonal lesion, which is chiefly mediated by the activation of receptors for advanced glycation end-products (RAGE). RAGE are also expressed in the endothelial layer, where it intensifies the progression of atherosclerosis. Henceforth, plausibly DP may be a surrogate marker of atherosclerotic cardiovascular disease among T2D individuals. Objective: We sought to investigate whether DP is related to the risk of atherosclerotic cardiovascular disease in T2D individuals. Methods: This was a prespecified analysis of the Brazilian Diabetes Study dataset. T2D subjects were screened for DP using the Michigan Neuropathy Screening Instrument (MNSI), which was deemed altered in all participants scoring 4 or more points in a 15-questions questionnaire, or in those scoring 2 points in a directed foot examination. Carotid doppler ultrasound was performed for intima-media thickness (C-IMT) measurement, and carotid disease (SCD) was considered for all with C-IMT higher than the 75th percentile validated for our population by the ELSA-Brasil Study. The relationship between SCD and DP was estimated by binary logistic regression, adjusted by the covariates: age, gender, A1c, LDL-C, hypertension, and prior cardiovascular disease. Results: Among 324 individuals (age: 58 + 7.1 years; 85% hypertensive; T2D duration: 9 + 6 years; 58.6% male; HbA1c: 7.8 + 1.6%), 134 (41.4%) had DP and 220 (67.9%) had SCD. Compared to non-DP, DP group had a higher prevalence of SCD (61.1% vs 77.5%; p = 0.002) and higher values of C-IMT (0.71 + 0.16 mm vs 0.78 + 0.19 mm; p < 0.001). DP was related to a SCD risk, with an OR of 2.21 (95%CI: 1.34, 3.64; p = 0.002), which remained significant after adjustment by age and gender (OR: 2.31; 95%CI: 1.28, 3.53; p = 0.003), and when further adjustment by A1c, LDL-C, hypertension and prior CVD was performed (OR: 3.38; 95%CI: 1.46, 7.81; p = 0.004). Conclusion: In T2D individuals, DP is independently related to SCD. Healthcare providers should thus consider DP screening as a potential tool when assessing individuals at higher risk of cardiovascular events. 108069 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Evaluation of the Clinical-Epidemiological Profile, Risk of Stroke and Bleeding in Patients with Atrial Fibrillation and End-Stage Renal Disease on Hemodialysis LUCAS YUJI SONODA1, Maria da Graca Lepre Hawerroth1, Jean Jose Silva2, Walter Alvarenga de Oliveira2 (1) Minas Gerais State University; (2) Santa Casa de Misericordia de Passos Introduction: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia and shares several common risk factors with end-stage renal disease (ESRD), as advanced age, hypertension, diabetes and vascular disease. Objective: To assess the clinical-epidemiological profile, risk of stroke and bleeding in patients with AF on renal replacement therapy undergoing hemodialysis in a regional hospital in Minas Gerais. Methods: A cross-sectional study, carried out in the nephrology sector of a hospital in the southwest of Minas Gerais, which included patients on renal replacement therapy on hemodialysis from January to March 2020. Patients with glomerular filtration rate (GFR) > 15 mL/min/1.73 m2, hemodialysis treatment for < 3 months, age < 18 years, and patients on peritoneal dialysis were excluded. All patients underwent a 12-lead electrocardiogram (ECG) during the hemodialysis session. The risk of stroke and major bleeding were calculated using the CHA2DS2VASC and HAS-BLED scores, respectively. Results: 247 patients from the hemodialysis sector were screened, of which 17 (6.8%) had AF on the ECG. Among patients with AF, 76% were male, the mean age was 72.5 +- 7.6 years. The mean GFR was 6.8 +- 3.1 mL/min/1.73 m2. The most common comorbidities were hypertension 14 (82.4%), smoking history 13 (76.4%), heart failure 11 (64.7%), diabetes 5 (29.4%), coronary artery disease 5 (29.4%) and stroke 3 (17.6%). The CHA2DS2VASC was >= 2 in 94.1% (mean 3.8 +- 1.5) of these patients. HAS-BLED scored >= 3 in 76.4% (mean 3.2 +- 1.1) of the cases. 3 (17.6%) of the patients were taking oral anticoagulants. Discussion: The prevalence of AF in patients with ESRD is approximately 11.6%, with a range from 4.5 to 27%. These patients have several conditions which increase the risk of stroke and also the risk of bleeding. However, to date, there is a lack of evidence on the safety and efficacy of oral anticoagulants in hemodialysis patients, remaining a dilemma in the management of these patients. Conclusion: In the present study, there was a prevalence of 6.8% of patients with AF on hemodialysis, with multiple comorbidities, high risk for both stroke and major bleeding and most were not receiving oral anticoagulation. 108079 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Prevalence and Risk Factors for Orthostatic Hypotension in Individuals with Type 2 Diabetes ANA RAQUEL WHITAKER FILIPE1, Ana Raquel Whitaker Filipe1, Sofia Helena Vitte1, Daniel Campos de Jesus1, Joaquim Barreto1, Andrei C. Sposito1 (1) Universidade Estadual de Campinas (UNICAMP) Introduction: Orthostatic hypotension (OH) is a surrogate marker of cardiovascular morbimortality in type 2 diabetes (T2D). The prevalence of OH is influenced by characteristics that significantly vary across populations. Objective: To determine the prevalence of OH and its risk factors in T2D Brazilian individuals. Methods: This was a cross-sectional, predefined analysis of the Brazilian Diabetes Study, a prospective ongoing cohort of T2D. Blood pressure (BP) was measured after 3-min resting using appropriately sized cuffs and the mean value of the last two out of three measurements were considered. Enrolees stood for 1-min for orthostatic BP. OH was defined as systolic or diastolic BP drops greater than 20 mmHg and 10 mmHg, respectively, or any OH-related symptoms. Baseline demographic and anthropometric data were recorded, and blood samples collected for biochemical analysis. The median family income was considered to classify study sample as high-income, whereas LDL-C > 100 mg/dL was deemed as high. Results: Among 1030 patients (mean age: 57 years; T2D duration: 9 years; 59% male), 104 (10,09%) had HO. Compared with non-HO, HO group was older (58 + 8.1 vs 60.4 + 7.5 years; p = < 0.001) and had a higher prevalence of female individuals (38.7% vs 58.7%; p < 0.001), high LDL-C levels (53.0% vs 65.8%; p = 0.038), low-income (15.2% vs 35.6%; p < 0.001), and of individuals with less than primary school education (15.1% vs 27.2%; p < 0.001). In binary logistic regression, the characteristics related to HO were age (OR: 1.046, 95%CI: 1.02, 1.07; p < 0.001), female gender (OR: 2.25, 95%CI: 1.49, 3.39; p < 0.001), high LDL-C (OR: 1.70, 95%CI: 1.02, 2.84; p = 0.040), whilst high-income (OR: 0.33; 95%CI: 0.17, 0.62; p < 0.001) and secondary education (OR: 0.31; 95%CI: 0.17, 0.57; p < 0.001, compared with less than primary education) were protective. After adjustment by covariates, female (OR: 2.16; 95%CI: 1.08, 4.34; p = 0.030) and secondary education (OR: 0.29; 95%CI: 0.09, 0.85; p = 0.025) were independently related to HO risk. Conclusions: OH affects 10% of Brazilian T2D subjects and its prevalence is higher among female and less educated individuals. This should be borne in mind when assessing OH status in this population. 108703 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Fake News in Cardiology - Study on the Online Dissemination of Fake News About Vaccine and Sudden Death ESTEPHANY DE JESUS SILVA1, Aline Goneli de Lacerda3, Claudio Tinoco Mesquita1 (1) Universidade Federal Fluminense - UFF; (2) Fundacao Euclides Cunha - FEC; (3) Pos Graduacao em Comunicacao - UFF Introduction: During the COVID-19 pandemic, the spread of fake news on social media took on such proportions that it was described by the World Health Organization as an "infodemic''. Sudden deaths of artists and athletes or by stroke have become associated with Covid-19 vaccines in social networks and message groups. As YouTube is the largest online video platform, our goal is to evaluate the spread of Fake News linking vaccines and sudden death on YouTube in Portuguese language videos. Methodology: We conducted a search for videos on Youtube Data Tools by the "Video Network", from the junction of the keywords "vaccine" AND "sudden death", from the crawl depth 0 of the tool to identify the most relevant actors (videos) on the topic on this platform. Then we used the software Gephi 0.9.2, for network analysis and visualization. Finally, we analyzed the content of the 99 most relevant videos to group them into 2 categories: "fake news" and "non-fake news". Results: Of the 99 videos, 17 were considered as fake news videos (18%), with a total of 2,289,355 views. The most watched fake news (673,175 views) related the death by stroke of a young man with the use of the COVID vaccine, although the hypothesis was ruled out by the health team in less than 6 months. In contrast we found 82 non-fake news videos, with the most viewed one accounting for 1,410,154 views. Videos with fake news often did not feature health professionals, and some were from mainstream media vehicles such as television newspapers. Conclusion: One in five of the most watched videos on YouTube linking vaccines and sudden death contain fake news. Although most videos are scientifically based, the dissemination of misinformation can contribute negatively to the health of the population by increasing hesitancy to vaccinate. Strategies to increase scientifically based cardiology content should be encouraged. 108356 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION D:A:Dr Seems to Agree Perfectly with Framingham Risk Score in a Brazilian Population Living with HIV VITOR QUEIROZ DE CASTRO SOUZA1, Victoria Valadares Andrade1, Thais Velasques Dias1, Carlos Roberto Brites Alves2, Eduardo Martins Netto2 (1) Faculdade de Medicina da Bahia (FMB/UFBA); (2) Laboratorio de Pesquisa em Infectologia (LAPI), Hospital Universitario Professor Edgard Santos (HUPES), Salvador, Brazil Introduction: People living with HIV (PLHIV) are twice as likely to develop cardiovascular disease. The identification of high cardiovascular risk (CVR) is essential to manage prevention strategies and can be performed through prediction equations. However, there is no validated CVR score for Brazilians living with HIV. Objective: To assess the agreement between three CVR scores in PLHIV. Methods: Cross-sectional study carried out with 265 Brazilians living with HIV, aged 40 to 74 years, using antiretroviral therapy. Ten-year CVR was calculated using two scores for the general population, the Framingham Risk Score (FRS) and the American College of Cardiology/American Heart Association (ASCVD), and one specific for PLHIV, Data Collection on Adverse Effects of Anti-HIV Drugs Cohort reduced (D:A:Dr). Multivariate logistic regression was performed to investigate the association of high CVR with statistically significant variables. Agreement between scores was assessed using the weighted Kappa coefficient and the Bland-Altman plot. The preventive recommendation with statins was analyzed, according to the Brazilian Clinical Protocol and Therapeutic Guidelines, through the use of scores. Results: The median age was 52 years (47-58), 58.9% were men, 46% brown, 11.3% were smokers, 34% were hypertensive, 9.1% were diabetic and 50.2% were overweight/obese. The median time of antiretroviral use was 15 years (7-21), 8.3% had a detectable viral load. Multivariate analysis showed that age, current smoking and diabetes mellitus were independent predictors for high CVR in the three scores. The agreement between the D:A:Dr and the FRS was perfect (k = 0.82; 95% CI 0.77-0.87; p < 0.001), and substantial between the FRS and the ASCVD (k = 0, 74; 95% CI 0.69-0.79; p < 0.001) and between D:A:Dr and ASCVD (k = 0.70; 95% CI 0.64-0.76; p < 0.001). The Bland Altman plot revealed greater discordance between scores as the RCV increased. The use of statins would be recommended for 25 patients when using the FRS, 8 with the ASCVD and 23 with the D:A:Dr. Conclusion: A high CVR was found in this study. The agreement between the FRS and the D:A:Dr suggests that both scores may be suitable for classifying the CVR in this population. There is still a need to develop calibrated equations for Brazilians living with HIV. Our results generate insights for the incorporation of D:A:Dr as an alternative to the FRS in the Brazilian protocol, as well as other international guidelines have been advocating. 108373 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Prevalence of Esophageal Injury After Atrial Fibrillation Ablation in Hospital Israelita Albert Einstein BEATRIZ HACHUL DE CAMPOS1, Denise Tessariol Hachul2, Cristiano Pisani3, Tan Chen Wu3, Alberto Ferraz3, Mauricio Ibrahim Scanavacca2 (1) FICSAE - Sao Paulo - Sao Paulo - Brasil; (2) Hospital Israelita Albert Einstein - Sao Paulo - Sao Paulo - Brasil; (3) INSTITUTO DO CORACAO DO HCFMUSP - SP - BRASIL Introduction: Catheter ablation of atrial fibrillation (AF) presents esophageal injury as a possible post-procedure complication. It is important to know its prevalence, to analyze the efficacy of protection techniques and establish early diagnosis and preventive treatment. Objective: To identify the prevalence of esophageal lesions in patients who underwent AF catheter ablation at Hospital Israelita Albert Einstein in a determined period. Methods: This is a retrospective study, with clinical follow-up based on the survey of medical records related to the perioperative period, of patients who underwent AF catheter ablation from 2016 to 2019. The esophageal mucosa evaluation was made by upper digestive endoscopy, performed between 24 and 72 hours after the procedure. Patients who showed severe injuries were selected to undergo a second endoscopy in the following week. The lesions observed were standardized by the Kansas City classification (KCC). Results: Fifty-seven patients were included in the study. Most of them were male (75.4%) with a mean age of 60.1 years old. Of the patients included, 75.4% had paroxysmal AF. In most cases (86%), a linear thermometer was used to avoid critical increase in the temperature and the occurrence of injury. In the other cases, esophagus displacement with a transesophageal Echo probe was carried out. Considering the esophageal injuries, 36 (63.2%) patients had no lesions in the endoscopy. Among the lesions observed, 1 (1.8%) had erythema (KCC1), 7 (12.3%) had erosion (KCC2A), 3 (5.3%) had hematoma-ecchymosis and 8 (14%) had traumatic injury. The overall prevalence of esophageal lesions was 34.5%. In the control endoscopy, performed in the following week, most of the injuries healed spontaneously, and no patient had complications during the medium and long terms follow-up. Conclusion: Despite protective measures, a considerable number of esophageal lesions was observed. Thus, this study suggests the need to improve the techniques of left atrium ablation and of esophageal protection. 108375 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Myocardial Insulin Resistance GABRIELA CORREIA MATOS DE OLIVEIRA1, Luis Matos de Oliveira2, Luis Jesuino de Oliveira Andrade3 (1) Faculdade de Medicina - UniFTC - Salvador - Bahia - Brazil.; (2) Faculdade de Medicina - Salvador - Bahia - Brazil.; (3) Colegiado de Medicina - Universidade Estadual de Santa Cruz - Ilheus - Bahia - Brazil. Background: The low available of Glut-4 transporters in sarcolemma of the cardiac cells is what characterizes the myocardial insulin resistance (MIR), which is triggered separately of generalized insulin resistance. Insulin receptors are quite evident in the heart muscle and vessels, and mitochondrial activity performs a significant function in MIR preserving cellular homeostasis by cell reproduction, cells livelihoods, and energy generation. Objective: It is to evaluate the MIR mechanism, and through the signaling pathway design. Methods: PubMed database was employed to search for reviews publications with MIR. The referenced data of the signaling pathway was chosen aggregating references of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A signaling pathway was designed based on MIR research manuscripts, where we show several mechanisms included in the MIR. The KEGG server was employed to exploit the interrelationship protein-protein, and elaborate signaling pathway diagram. The signaling pathway mapping was carried out with PathVisio software. Results: We selected 42 articles from a total of 450 articles in the PubMed database that presented a significant association between the terms "insulin resistance myocardial" AND "signaling pathway". Founded on database-validated research papers, we choose well-founded pathways and we succeeded representative description of these pathways. The reproduction contigs taken from the KEGG database designed the signaling pathway of the bio-molecules that lead to MIR. Thus, the acting among multiple mechanisms releases factors that participate of the development of MIR. Conclusion: The interaction among various mechanisms and molecular interactions are important factors in development of MIR. 108661 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Mortality and Outcomes After Correction of Aortic Stenosis by Surgical Replacement and Transcateter in Sergipe - Smallest State of Brazil GABRIELA DE OLIVEIRA SALAZAR1, Jose Icaro Nunes Cruz1, Claudia Bispo Martins-Santos1, Mayara Evelyn Gomes Lopes1, Ullany Maria Lima Amorim Coelho de Albuquerque1, Marilia Marques Aquino1, Juliana Maria Chianca Lira1, Nathalia Luiza Silva Sobral1, Lucas Villar Shan de Carvalho Cardoso1, Antonio Carlos Sobral Sousa2, Joselina Luzia Menezes Oliveira2, Eduardo Jose Pereira Ferreira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Lucas Hospital; (3) Primavera Hospital Introduction: The symptomatic manifestation of aortic stenosis (AoS) represents a considerable increase in the risk of death and indicates valve replacement, either by transcatheter route (TAVR) or by conventional transthoracic surgery (SAVR). Recent studies seek to compare the results and complications between these procedures, with attractive results for TAVR, especially after the development of more modern prostheses. Objective: To compare hemodynamic outcomes, mortality and in-hospital complications in patients with severe AoS treated in SAVR and TAVR in Sergipe (Brazil). Methods: Retrospective, observational and analytical cohort study. It included data collected between 2013 to 2021 based on medical records. Fifty-five patients were included, divided into groups according to treatment for severe aortic stenosis, SAVR (17; 30.9%) or TAVR (38; 69.1%). Statistical analysis was performed using the Student's T test, indicated by the Shapiro-Wilk test, in addition to the chi-square test or Fisher's exact test. A significance level of 5% was adopted. Results: The mean age of the sample was 76.6 +- 10.93 years. Of the total, 59.3% were male. Of the TAVRs (38), all were via transfemoral access and the most used prostheses were EVOLUT R (64.7%), followed by COREVALVE (17.6%) and SAPIEN 3 (8.8%). In SAVR (17), bovine pericardium bioprosthesis was the most used (80%). Patients in the TAVR group had a higher surgical risk profile according to the EuroSCORE I, II and STS scores (p < 0.05). The mean length of hospital stay was 11 days for both groups and hospital mortality was 8.5% for TAVR and 5.9% for SAVR (p > 0.05). There were no differences regarding the percentage of improvement in the echocardiographic parameters after the procedure, regarding the development of conduction disturbance or cardiac rhythm alteration (p > 0.05). However, there was more mild and moderate paravalvular regurgitation in the TAVR group (p = 0.03) and more major or minor bleeding complications (p = 0.046) and acute renal failure (p = 0.017) in the SAVR group. Conclusion: Patients with severe AoS treated by SAVR and TAVR had similar results in terms of valvular hemodynamic performance, mortality rate and mean hospital stay. Patients in the TAVR group had a higher rate of paravalvular regurgitation and those in the SAVR group had more bleeding complications and acute kidney injury. 109089 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Use of Electronic Cigarettes and Its Impacts on the Cardiovascular System BRUNA GUIMARAES AGUIAR1, Ana Christina Beltrao de Souza Guerra Curado2, Jose Felipe Valois Ribeiro Silva1, Paulo Borges Santana3 (1) Centro Universitario Mauricio de Nassau (UNINASSAU); (2) Faculdade Pernambucana de Saude (FPS); (3) Hospital Agamenon Magalhaes (HAM) Introduction: The use of traditional cigarettes (TC) is still a major public health problem, having negative effects on the cardiovascular system (CVS), despite incentives to reduce its use. The electronic cigarette (EC) appears aiming to replace the TC, releasing nicotine without containing the smoke of the latter. However, ECs are not pharmacologically controlled products, leading them to have an even higher nicotine content than CT. Objectives: Analyze the cardiovascular effects of EC use, as well as the harm caused by the chemical products present in cigarettes. Methodology: A systematic review was carried out using a search for scientific articles on Scielo and PubMed, in March 2022, without language and year restrictions, using the descriptors: "Cardiovascular System", "Cardiovascular Disease", "cigarette electronic" associated to the Boolean operator AND. Results and Discussion: 98 articles were found, of which 83 were discarded by reading the titles, 10 by reading the abstracts, since they were not related to the research purpose, being selected 5 articles for complete reading, and all were used for the research. ECs work by heating and releasing vapors that produce toxic substances, including nicotine. Its use is related to high cytotoxicity and changes in cell morphology, which negatively affects endothelial function and the supply of nitric oxide, resulting in an increased risk on CVS. These users, when compared to non-smokers, have twice the risk of having a myocardial infarction, and may have worsened CVS ongoing pathologies, since nicotine, which is also related to dependence, has repercussions on hemodynamics, coronary blood flow, angiogenesis, hypertension and inflammation. Paradoxically, the concentration of nicotine in EC is higher than in CT, and can vary from 16 to 21 mg/mL. In addition, the use of EC increases the risk of atherosclerosis, due to changes in low-density lipoprotein (LDL). Conclusion: Smoking is a relevant health problem, being an important risk factor for heart disease. EC may contain an even higher nicotine content than CT, due to the lack of pharmacological control. The risk of myocardial infarction is greater in smokers than in non-smokers. In addition, nicotine affects hemodynamics, angiogenesis and worsens atherosclerosis. Furthermore, further studies on this topic are needed to broaden the understanding of the EC's repercussions on public health. 108460 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Remote Monitoring of Cardiac Devices During the COVID-19 Pandemic. Timely and Effective? EDUARDO AUGUSTO QUIDUTE ARRAIS ROCHA1, Luis Gustavo Bastos Pinho3, Juvencio Santos Nobre3, Pedro Sales Pereira Gondim1, Arthur Holanda Dantas1, Pedro Barbosa Duarte Vidal3, Aston Alves de Freitas1, Vitor Olimpio Coimbra1, Davi Sales Pereira Gondim2, Bruna Sobreira Kubrusly3, Fernanda Pimentel Arraes Maia3, Francisca Tatiana Moreira Pereira4 (1) Centro Universitario Christus (Unichristus); (2) Universidade de Fortaleza (Unifor); (3) Universidade Federal do Ceara (UFC); (4) Centro de Arritmia do Ceara (CACE) Introduction: The COVID-19 pandemic determined great difficulty or even the impossibility of ambulatory follow-up for several patients, including those with heart disease and those with implanted electronic cardiac devices (IECD). These patients need special monitoring for testing and programming their devices. The groups with remote monitoring (RM) could be followed during the pandemic at a distance. It is important to analyze the results of this population, including the possibility of expanding this form of monitoring in Brazil. The aim of this study was to analyze the findings of IECD followed by RM during the COVID-19 pandemic. Methods: Cohort, observational, prospective study involving 119 patients. Events detected in the RM were: presence of atrial and ventricular arrhythmias, defibrillator therapies, changes in the battery, electrode or heart failure parameters. Comparisons were performed using the chi-square test and paired student t test, with p < 5% considered significant. The numbers of events during the pandemic (Group 1-G1) and before the pandemic (Group 2-G2) were compared, with the patient initially being used as his own control. Then, the event rates of G-1 were compared with the group followed just before the pandemic period (Group 3-G3). Results: The patients were 30.2% female, with a mean age of 72 +- 14.2 years, ejection fraction of 55% (34.5/57%), and these types of devices: 30.2% pacemaker; 42, 8% with defibrillator, 3.3% biventricular pacemaker and 22.7% with defibrillator/biventricular pacemaker. 58.8% of the patients in the study had events in the pandemic. Group 1 hadn't a higher number of events when compared to its own control (G2), RR 1.03 (CI 95% 0.83-1.28), or in relation to group 3, RR 1.02 (CI 95% 0.81-1.30). The groups followed during the pandemic and outside the pandemic showed no differences in characteristics such as age (p = 0.86), ejection fraction (p = 0.08) or functional class > II (p = 0.25). Conclusions: During the COVID-19 pandemic, patients with IECD followed by RM had a high number of monitored events. The COVID-19 pandemic hasn't determined increases in arrhythmic events in the population of this study. The RM should be considered as an additional form of follow-up for patients with IECD in Brazil. 108718 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Independent Predictors of Low Cardiorespiratory Fitness in Patients with Myocardial Ischemia on Exercise Stress Echocardiography JOSE ICARO NUNES CRUZ1, Gabriela de Oliveira Salazar1, Claudia Bispo Martins-Santos1, Juliana Maria Chianca Lira1, Edvaldo Victor Gois Oliveira1, Lara Teles Alencar Duarte1, Ullany Maria Lima Amorim Coelho de Albuquerque1, Myllena Maria Santos Santana1, Lucas Villar Shan de Carvalho Cardoso1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital Introduction: Cardiorespiratory fitness (CF), quantified in Metabolic Equivalent of Task (MET), has an inverse relationship with cardiovascular morbidity and mortality. It is estimated that an increase of 1 MET to the CF reduces mortality from all causes from 11.6% to 15.0% and from 16.1% to 19.0% mortality from cardiovascular causes. Objectives: To determine the predictors of low CF in patients with myocardial ischemia. Methods: Cross-sectional, analytical study, whose inclusion criterion was the diagnosis of myocardial ischemia on exercise stress echocardiography. The criterion for low CF was MET < 7.9. A multivariate analysis using binary logistic regression was performed to determine risk and protective factors for low CF in patients with myocardial ischemia. The Nagelkerke pseudo R-squared for the model was 39.3%. The analyses were performed using SPSS Statistics software, version 22.0. Results: 1443 patients were included in the study, of which 56.1% were male (809) and 37.8% had low CF (545). Predictors of low CF were smoking or ex-smoking, chronotropic incompetence, female sex, sedentary lifestyle, typical chest pain, systemic arterial hypertension (SAH), diabetes mellitus (DM) and age. Individuals with asymptomatic myocardial ischemia were 57.3% less likely to have low CF. Left ventricular ejection fraction (LVEF) was also a protective factor - an increase of 1% in LVEF provided 4.2% greater protection against low CF (Table 1). Conclusions: Smoking, female sex and sedentary lifestyle are strong predictors of low cardiorespiratory fitness. It has also been demonstrated that chronotropic incompetence, typical chest pain, SAH and DM are risk factors for low CF. In addition, the absence of symptoms and preserved LVEF confer a lower risk of low CF in ischemic patients. 108927 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Profile of a Young Adult Population with High Risk for Obstructive Sleep Apnea Screened by Stop-Bang and Epworth Sleepiness Scale in a Primary Health Care Unit TOMAS DE SOUZA MELLO1, Karine da Silva Guimaraes1, Gabriela Gama Zagni Jardim1, Ana Rachel Bucar Cervasio1, Clara Avelar Mendes de Vasconcellos1, Juliana Camara Garcia1, Rodrigo Eugenio Vinuto Borges1, Natalia Rossilho Moyses Ushijima1, Luiza Brandao Catharina1, Luisa Leite Vaz da Silva1, Ana Cristina Tenorio da Costa Fernandes1, Elizabeth Silaid Muxfeldt1 (1) IDOMED - Universidade Estacio de Sa, Medicine School, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil. Objective: To establish the relationship between cardiovascular (CV) risk profile and detected risk of Obstructive Sleep Apnea (OSA) in two questionnaires - STOP-BANG (SB) and Epworth Sleepiness Scale (ESS), in a young population of adults registered in a Primary Health Care unit in Rio de Janeiro, Brazil. Design and Methods: This cross-sectional population study enrolled adults between 20-50 years old, registered in a primary healthcare unit in Rio de Janeiro. A database is being developed including sociodemographic and anthropometric data, and CV risk factors. Office blood pressure and Home Blood Pressure Monitoring (7-day protocol) (Omron-705CP). Moreover, OSA was investigated by SB and ESS. Patients with a high risk for OSA in either of these two questionnaires were subsequently assigned for polysomnography. Results: A total of 562 subjects were evaluated [40% males, 38.9 +- 8.8 years], where 151 (26.9%) were identified as high risk for OSA by the SB questionnaire and 210 (37.4%) by ESS. The most common CV risk factor was physical inactivity (43%), followed by dyslipidemia (38%) and obesity (28%). By Office blood pressure, the prevalence of hypertension was 13.4% while by Home Blood Pressure Monitoring was 18.6%, with a low concordance between them (kappa = 0.472). Subjects with a high risk at SB are older, with a higher prevalence of obesity, hypertension and higher Office blood pressure and Home Blood Pressure Monitoring. On the other hand, individuals with high-risk by ESS were more obese, with increased waist circumference, higher prevalence of dyslipidemia and metabolic syndrome. Nevertheless, there was no difference in Office blood pressure levels. Among the subjects submitted to polysomnography, 46% had a diagnosis of OSA (AHI >= 5/hour) and 23% of moderate/severe OSA (AHI > 15/hour). The best predictor of AOS was SB, positive in 100% of subjects with moderate/severe OSA, while ESS was positive in only 20% of them. Conclusion: This young and apparently healthy population presented a high prevalence and risk for OSA. The SB had a higher association with higher Office blood pressure levels, while ESS was associated with a worse metabolic profile. SB questionnaire seems to be the best predictor for moderate/severe OSA in this young adult population. 108480 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Gender Impact on Mortality Rates of Patients with Heart Failure Stratified by a New Classification Proposal: A 5-Year Follow-Up in a Hospital in Southern Brazil ALINE PETRACCO PETZOLD1, Fernanda Lourega Chieza3, Luiz Claudio Danzmann2, Luiz Carlos Bodanese1 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS); (2) Universidade Luterana do Brasil (ULBRA); (3) Hospital Sao Lucas da PUCRS Introduction: Gender differences in the epidemiology of heart failure (HF) have been suggested. Findings reinforce that women respond differently to left ventricular ejection fraction (LVEF) values and HF treatment. Objectives: To compare survival between sexes in HF patients, stratified by LVEF values, in a new proposal (< 40%, between 40-59% and > 60%), in a 5-year cohort follow-up. Methods: This is a retrospective cohort study in which the 5-year mortality rates of 385 patients, was analyzed. The sample was divided into three groups: LVEF <= 40% (n = 133), LVEF 40-59% (n = 145) and LVEF >= 60% (n = 107), differentiating the sexes in each group. Inclusion criteria were age > 18 years, previous diagnosis of HF and transthoracic echocardiogram. The logrank test and Kaplan-Meier curve were used. Results: Patients with lower LVEF were younger, for both sexes. High mortality among all groups was observed. The main HF cause was, for women, hypertension, and, for men, ischemic heart disease. In a 5-year analysis, the mortality rates for each LVEF group and sex were compared (Table 1). The mortality rates found were similar between sexes, thus our results go against women responding differently to LVEF values and to HF treatment. Conclusions: No statistically significant difference was found in survival between the sexes, comparing the different LVEF groups. There is a need for better assessment of the HF population, since all mortalities found were high. 108512 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Reduction in Elective Cardiology Diagnostic Tests and Procedures During the COVID-19 Pandemic in Brazil DANIEL MARQUES DA SILVA1, SEVERINO PEIXOTO NUNES NETTO2, LETICIA STEPHANIE DE SOUZA ARAUJO3 (1) UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE (UFRN); (2) UNIVERSIDADE FEDERAL DE UBERLANDIA (UFU); (3) UNIAO SOCIAL CAMILIANA (USC) Introduction: During the COVID-19 Pandemic's first three months in Brazil, a decrease in Elective Cardiology Diagnostic Tests and Procedures (ECDTP) was reported, which can be associated with deficient planning of cardiovascular disease (CVD) management and may have contributed to the increase of in-hospital fatality due to CVDs. Objective: To analyze the impact of the Pandemic on the amount of ECDTP performed at Brazilian Unified Public Health System (SUS) in 2020 and 2021. Methods: We evaluated the number of ECDTP performed at SUS between March and December of each year from 2015 to 2021 from the Brazilian Outpatient Information System (SIA/SUS). The data until 2019 was used to project the number of ECDTP expected in 2020 and 2021 by a linear regression using a statistical significance level of 0.05 (P-value = 0.0026 for both angular and linear coefficients). The projection was compared to the real data from 2020 and 2021. Results: The linear regression until 2019 presented a R-squared of 0.967, which showed a rising trend of ECDTP performed per year before the Pandemic. The data recorded in 2020 was 38.65% lower than the predicted. It showed that the cardiovascular care provision was notably affected by the pandemic due to SUS rearrangement to attend COVID-19 requirements. In 2021, after the mass immunization campaign in Brazil, the ECDTP returned to a rising trend, with 21.39% increase compared to 2020. Despite the improvement, in 2021 the real data was 29.14% lower than the amount predicted. Conclusions: Rearrangements to address COVID-19 requirements affected the amount of ECDTP performed. This effect was mainly noted in 2020, but was still remarkable in 2021 even with the immunization campaign. This situation may have resulted in the neglection of cardiovascular diseases. 108536 Modality: E-Poster Scientific Initiation - Non-case Report Category: ANTICOAGULATION Venous Thromboembolism in Patients Hospitalized for -2: A Systematic Review ESTEVAO OLIVEIRA CARVALHO1, Joao Ricardo Nogueira Perez1, Gabriela Billafan Ferreira1, Lucas Lagares Braganca Magami1, Luan de Castro Franca1, Leandro Guedes Santos1, Diana Aristotelis Rocha de Sa1 (1) ESCOLA SUPERIOR DE CIENCIAS DA SAUDE (ESCS) Introduction: The coronavirus disease 2019 (COVID 19), caused by Sars-CoV-2 virus, according to stipulations, claimed about 18,2 million lives until December 31, 2021 . The COVID-19 generates a hypercoagulability state. Therefore, the main guidelines [2-3] recommend thromboprophylaxis in hospitalized COVID-19 patients. However, doubts remain about the use of low-molecular-weight heparin (LMWH). Aim: To analyze the incidence of venous thromboembolism in hospitalized patients with COVID-19 in the regime of thromboprophylaxis with LMWH. Method: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) rules. EMBASE and PubMed were the selected databases. The following health descriptors were used: "venous thromboembolism" "COVID-19", "coronavirus disease 2019", "anticoagulant" and "anticoagulants agent". Two authors independently performed a systematic literature search in databases. A search encompassed that was published between 01/01/2019 until 31/12/2021. The studies eligible for inclusion had a population over 18 years old, with confirmed diagnosis of COVID-19, hospitalized, and all population did use exclusively LMWH Articles were excluded if they did not provide data about prophylactic anticoagulation regimen (PAR) and if they are case reports. Two authors (E.O.C and J.R.N.P) realized the data collection process, in an independent form. Results: Our search found 202 articles, of which 80 were duplicates. A total of 122 titles were excluded after reading the title and abstract. Therefore, 17 articles were selected for reading the full-text. In this step, 5 titles were excluded, because they don't give information about the PAR and 3 because they don't use LMWH exclusively. So, we selected 9 titles [4-12]. A total of 1614 participants, from 8 countries, submitted to prophylaxis with LMWH. Being that 160 participants (9,91%) had a venous thromboembolic event. 6 articles [6-11] gave information about bleeding that occurred with 43 participants (3%). Conclusion: The proportion of thrombotics events in hospitalized patients diagnosed with COVID-19 is 18% to 37%, without prophylactic anticoagulation . Our research demonstrated that less than half of the population submitted to prophylaxis anticoagulation evolved to venous thromboembolic events. 109325 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Prevalence of Transthyretin Cardiac Amyloidosis in a Population Previously Diagnosed with Hypertrophic Cardiomyopathy LEONARDO SANTANA ANDRADE1, Emerson Santana Santos1, Braulio Cruz Melo1, Antonio Guilherme Cunha de Almeida1, Joao Victor Andrade Pimentel1, Larissa Rebeca da Silva Tavares2, Vinicius Barbosa dos Santos Sales1, Julia Souza Diniz1, Joao Paulo Dias Costa1, Irlaneide da Silva Tavares1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe; (2) Universidade Tiradentes Introduction: Transthyretin amyloidosis (ATTR) is one of the hypertrophic cardiomyopathy (HCM) phenocopies. It is caused by pathogenic variants in the transthyretin (TTR) gene and occurs in five per cent of patients with unexplained HCM. Aims: Estabilish the prevalence of ATTR in a population previously diagnosed with HCM. Methods: A prospective study was conducted and a 168 genes panel related to cardiomyopathy was performed. HCM was diagnosed according to the guidelines of the American Heart Association (AHA). Results: The TTR gene was sequenced in 74 index patients referred to our cardiogenetics outpatient clinic between January 2021 and March 2022. Among the included patients, 4 had positive diagnosis for ATTR and other major clinical findings are summarized on Table 1. Conclusion: The prevalence of ATTR was similar to literature. Our study highlights the importance of early diagnosis for ATTR since treatment has higher rates of effectiveness when administered in the early stages, it also reinforces that phenocopies, such as the ATTR, should always be included in differential diagnosis investigations for patients with unexplained HCM. Keywords: Transthyretin amyloidosis, Hypertrophic Cardiomyopathy, Genetic Panel. 108685 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Prevalence and Risk Factors of Delirium in Post-Operative Period of Heart Surgery ARTHUR MAROT DE PAIVA2, Gabriel Baeta Branquinho Reis2, Luiz Fernando Sposito Ribeiro Baltazar2, Pedro Guimaraes Moreira da Silva2, Walace Chaves dos Santos1, Mauricio Lopes Prudente1, Abissay Francisco Dias1, Marcos Vinicius Pires Rodrigues1, Thaina Lopes de Souza1, Joao Alberto Pansani1, Artur Henrique de Souza1, Giulliano Gardenghi1 (1) Hospital ENCORE - Aparecida de Goiania/GO; (2) Universidade Federal de /GO Introduction: Delirium is an acute mental status change, with a fluctuating course and a high incidence in cardiac surgery post-operative (PO) period. Delirium can lead to both short and long-term consequences. Objective: Describe the prevalence of delirium in patients summitted to cardiovascular surgery. Methods: This is a descriptive cross-sectional study with patients summitted to cardiac surgery between January 2020 and February 2022. The assessment of delirium was performed on the 1st PO in the Intensive Care Unit using the CAM-ICU and RASS scales. The evaluation of epidemiological data, previous comorbidities, use of pre and post-operative medications, anthropometric measurements and information related to the surgery were collected from TASY(r) electronic medical record. Data collected and tabulated using specific spreadsheets with Excel 2010(r) software. Results: 74 patients (39 men) were included. The prevalence of delirium was 16.2%. In patients with delirium, 50% were males and in those without delirium, 53.3% were males. The mean age in those with delirium was 72(+-7.9) years old and the mean of BMI was 25.6(+-2.89), while those without delirium was 57.2(+-12.9) and 27.8(+-4.1), respectively. In patients with delirium, 58.3% was summitted to general anesthesia associated with spinal anesthesia and in 41.6% general anesthesia was used alone. In patients without delirium, 61.3% underwent spinal anesthesia plus general anesthesia and in 38.7% only general anesthesia. In patients with delirium, the mean cardiopulmonary bypass (CPB) time was 100.7(+-31.34) minutes, and the mean aortic clamping time was 70(+-27.3) minutes. In those without delirium, the mean time of CPB was 97.5(+-26.6) minutes and the aortic clamping time was 69.4(+-22.6) minutes. Regarding comorbid diseases, the mean was 5.08(+-2.27) in patients with delirium and 3.2(+-2.2) in those without delirium. With respect of the number of medications used, in patients with delirium, the mean home medications used was 5(+-2.1) and the mean of post-operative medications was 7.8(+-1.9). While, in patients without delirium the mean number of medications used was 4.1(+-2.1) and post-operative used was 7.5(+-1.9). Conclusion: The prevalence of delirium found in the sample was consistent with current literature data. Considering patients with delirium, multiple risks factors were observed, such as advanced age, greater number of comorbidities and pre and post-operative polypharmacy. 108757 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Are Elderly Patients with Hypertension Still using Potentially Inappropriate Medications? an Observational Study with Secondary Data TAINA SILVEIRA ALANO1, Larissa Xavier Neves da Silva3, Guilherme Lucca Casali3, Jayne Santos Leite3, Andresa Conrado Ignacio3, Linda Ariene dos Santos Cardoso1, Daniel Umpierre2 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (2) Hospital de Clinicas de Porto Alegre (HCPA); (3) Universidade Federal do Rio Grande do Sul (UFRGS); (4) Prefeitura Municipal de Porto Alegre (PMPA) Background: The elderly are the most medicalized age group in society. Due to their metabolism changes, many commonly used drugs are no longer appropriate, with their risks outweighing the benefits. When the patient already has a chronic disease, the prescription should be even more responsible. The Beers Criteria for Potentially Inappropriate Medications (PIMs) is a systematic cataloging of the existing evidence in this field, aiming to improve the healthcare of the elderly. Objectives: Assess the prevalence and characterize the use of PIMs in older adults with hypertension enrolled in research studies in the city of Porto Alegre. Methods: Cross-sectional study of secondary data. The population was composed of individuals aged 60 years or older and diagnosed with systemic arterial hypertension (SAH). The data were retrieved from 2 studies carried out in the city of Porto Alegre between 2018 and 2020. Based on the answers to a General Health Questionnaire, the prevalence of PIMs was analyzed using the 2015 Beers Criteria. Drugs with minimum dosage requirements were excluded from the analysis. The data analysis was performed using Python 3.9. The pre-analysis plan, statistical codes, and dataset used for this study are available at osf.io/ksfg2. Results: There were 318 hypertensive patients (71% female) included, with a mean age of 69 years old (standard deviation 6.4). A total of 32 different PIMs were found, with the most prevalent being omeprazole, used by 30 (9%) patients. A total of 88 (28%) patients were using at least one PIM. Considering sex, 23% of males and 30% of females were using PIMs. Patients aged from 60-69, 70-79, and 80-89 years old had a prevalence rate of using at least one PIM of 28%, 27%, and 30%, respectively. Conclusions: There is still a notable usage of PIMs in the elderly with SAH, with the highest rates being in females and octogenarians. The existing literature on this subject is inconclusive, with prevalences ranging from 24% to 82%. The results reflect the need for better pharmacological and geriatrics training for healthcare professionals and the empowerment of the patient in the prescription process. This study presents some limitations, such as the absence of the full illness history and a possible selection bias, since the participants were already involved in health-related scenarios. Further studies could explore interventions of education on responsible prescribing and self-medication risks in hypertensive elderlies. 108639 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Down Syndrome and Congenital Heart Diseases: Clinical and Cytogenetic Characteristics of Patients Admitted to a Cardiac Intensive Care Unit of a Pediatric Hospital LETICIA VIEIRA SENGER1, Rafael Fabiano Machado Rosa1, Helena Guedes da Rocha1, Helena Marcon Bischoff1, Grasiele do Amaral Martins1, Georgia Marques Jardim1, Alexandre Perin Decol1, Matheus Ribeiro Fretes1, Bianca Brinques da Silva2, Estefany Karenine Rodriguez Casanova1, Carolina Feijo Bombana1, Carolina Andreatta Gottschall2 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (2) Universidade Luterana do Brasil (ULBRA) Introduction: In children with Down Syndrome, there is a high prevalence of congenital heart diseases, which characterize anomalies associated with hospitalization and surgical correction. Objectives: To investigate incidence, clinical presentation and cytogenetic characteristics of patients with Down syndrome (DS) and congenital heart disease (CHD) who are admitted to a cardiac Intensive Care Unit (ICU) of a pediatric hospital. Methodology: A prospective and consecutive cohort of patients hospitalized for the first time by CHD in the Cardiology ICU of the Santo Antonio Children's Hospital was evaluated for 1 year. For each patient, a standard clinical protocol was applied, with abdominal ultrasound and karyotype examination. Results: 207 patients composed the sample and karyotype could be performed in 204. Chromosomal alterations were observed in 29 individuals, 24 of them (12%) with DS (23 by trisomy free of chromosome 21 and 1 by isochromosome 21q). The main CHDs observed in these patients were septal defects (n = 18), especially the atrioventricular septal defect (AVSD), present in half of the cases. DS was the cause of AVSD in 55% of the cases of the sample, and the association of this defect with DS was statistically significant. There was no difference in the frequency of alterations detected on abdominal ultrasound, length of hospital stay and deaths among patients with DS and normal karyotype. Conclusions: The frequency of DS found in our study, as well as the types of chromosomal abnormalities identified in these patients, were in accordant with the literature. In our series, patients with DS presented a good evolution, similar to patients with normal karyotype, as described in other studies. 108640 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Percutaneous Correction of Interatrial Communication (IAC) in Adults in a High Complexity Cardiology Service in Brazilian Western Amazon: A Case Series LEO CHRISTYAN ALVES DE LIMA1, Leo Christyan Alves de Lima1, Elaine Largura Biazati1, Willian Kubo1, Hildeman Dias da Costa2, Alexandre Venturelli da Silva3, Fabiana Cristina Schabatoski Passos3, Luiz Henrique Gasparelo3 (1) Liga Rondoniense de Cardiologia Clinica e Cirurgica (LICAR); (2) Universidade Federal de Rondonia; (3) Angiocenter Introduction: Interatrial communication (IAC) is one of the most common congenital heart diseases, affecting one in 800 births, characterized by a defect in the closure of the interatrial septum. Due to its slow evolution, it is usually diagnosed late in adulthood, when symptoms result from right heart failure, pulmonary hypertension with cor pulmonale or atrial arrhythmias. Objectives: This is a descriptive study of the registration of cases of IAC correction performed in a high-complexity service in the Western Amazon. Methods: Data obtained through research via medical records and complementary exams were used. The database selection was through Pubmed and Scientific Electronic Library On-line (SCIELO). Results: Five patients were followed, one male and four female, all of them with symptoms of dyspnea on exertion and fatigue. The transthoracic echocardiogram showed an ostium secundum (OS) IAC, with signs of right chamber overload and pulmonary hypertension (mild to moderate). The prostheses were implanted through the right femoral vein and with the aid of intracardiac echocardiography. Although vascular complications are known, in this small serious there were no complications during the procedures. The prostheses used were Coccum(r) in one case and Amplatz(r) in four cases. The patients had a hospital stay of less than two days and in the outpatient follow-up they showed a favorable evolution. Discussion: The indication for percutaneous IAC closure are patients who have ostium secundum (OS) +96 with favorable anatomy associated with symptoms or with any degree of pulmonary hypertension, right chamber overload, as described in this work. In addition, percutaneous closure is a less invasive alternative and is associated with fewer thromboembolic complications compared to the traditional surgical method. Conclusion: Despite a smaller number of cases than most large centers, positive results can be seen in this type of treatment. The percutaneous treatment of OS type IAC is a safe procedure and performed in the state without the need to transfer to other locations, improving the patient's quality of life with a relatively low risk and increasing their life expectancy. 108643 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Influence of Clinical Characteristics on Therapeutic Indication for Aortic Stenosis in Sergipe - the Smallest Brazilian State JOSE ICARO NUNES CRUZ1, Gabriela de Oliveria Salazar1, Claudia Bispo Martins-Santos1, Mayara Evelyn Gomes Lopes1, Ullany Maria Lima Amorim Coelho de Albuquerque1, Marilia Marques Aquino1, Lucas Villar Shan de Carvalho Cardoso1, Edvaldo Victor Gois Oliveira1, Joselina Luzia Menezes Oliveira2, Enaldo Vieira de Melo1, Eduardo Jose Pereira Ferreira2, Antonio Carlos Sobral Sousa2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital Introduction: Aortic stenosis (AoS) is the restriction of blood outflow through the aortic valve leaflets during ventricular systole. When symptomatic, AoS can be treated with valve replacement, which can be performed percutaneously (TAVR) or by conventional transthoracic surgery (SAVR). Objectives: To evaluate the influence of clinical variables and surgical risk on therapeutic indication for AoS in Sergipe - the smallest Brazilian state. Methods: This is an observational, cross-sectional, analytical study, conducted in two private hospitals in Sergipe (Brazil). The sample included patients who underwent TAVR or SAVR after diagnosis of severe AoS defined by echocardiographic criteria and symptomatological assessment, between 2013 and 2021. The TAVR and SAVR groups were compared in terms of comorbidities and surgical risk scores. Categorical variables were analyzed using Fisher's exact test, whereas quantitative variables were analyzed using Student's t-test or Mann-Whitney U test. The statistical analysis was performed using SPSS Statistics software, version 22.0. Results: The sample included 55 patients, of which 38 underwent TAVR and 17 underwent SAVR. The TAVR and SAVR treatment groups did not demonstrate differences in sex, height and weight distributions, however age was higher among those who underwent TAVR (88 vs. 62 years; p < 0.001). The TAVR group exhibited more patients in functional class III or IV (New York Heart Association) compared to the SAVR group (88.6% vs. 40.0%; p < 0.01), as well as higher prevalence for diabetes mellitus (46.2% vs. 5.9%), dyslipidemia (76.0% vs. 31.3%) and chronic kidney disease (78.6% vs. 33.3%) (p < 0.05). The four surgical risk scores assessed were also higher in the TAVR treatment group: logistic EuroSCORE I (15.6% vs. 6.7%; p < 0.05); EuroSCORE II (7.0% vs. 2.9%; p < 0.01); STS mortality score (5.3% vs. 1.7%; p < 0.05); and STS morbidity or mortality score (29.5% vs. 11.5%; p < 0.05). Conclusions: Patients treated with TAVR presented older age, greater severity of heart failure, greater frequency of comorbidities, in addition to exhibiting a greater surgical risk profile according to the 30-day mortality prediction scores. Although the guidelines recommend TAVR for patients at higher surgical risk, this treatment was also expanded to intermediate-risk patients in Sergipe. 108657 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Diagnostic Accuracy of Coronary Angiotomography for Coronary Artery Disease in Sergipe - the Smallest Brazilian State JOSE ICARO NUNES CRUZ1, Claudia Bispo Martins-Santos1, Gabriela de Oliveira Salazar1, Juliana Maria Chianca Lira1, Myllena Maria Santos Santana1, Ana Luisa Lisboa Prado1, Giulia Vieira Santos1, Leticia Luiza Gomes Marques1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2, Luiz Flavio Galvao Goncalves2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital Introduction: Coronary angiography is the gold standard test for the diagnosis of coronary artery disease (CAD). In recent years, with the advent of coronary computed tomography angiography (CCTA), the possibility of non-invasively diagnosing CAD has emerged. However, in order to validate CCTA locally, it is necessary to assess its diagnostic accuracy in a northeastern brazilian state, where the use of CCTA has recently been expanded. Objectives: To determine the diagnostic accuracy of CCTA in a sample from Sergipe, considering coronary angiography as the gold standard test. Methods: This is an observational, cross-sectional, analytical study. The sample included patients with cardiovascular complaints who underwent CCTA and coronary angiography at an interval of less than six months, in Sergipe (Brazil). The identification of plaques associated with luminal narrowing of any degree was considered positive for CAD. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and Receiver Operating Characteristic (ROC) curve were evaluated to determine the diagnostic potential of CCTA for CAD, considering coronary angiography as the gold standard method. Results: 130 patients were included in the study. The median age was 62 years (IQR: 57.0-67.25). The prevalence of CAD determined by the gold standard test was 76.9% (100). The CCTA showed a sensitivity of 95.0%, specificity of 80.0%, PPV of 94.1%, NPV of 82.8% and accuracy of 91.5%. The area under the ROC curve demonstrated significant discriminatory capacity (0.875; CI95% 0.79-0.96; p < 0.001) . Conclusions: The study results are consistent with those observed in meta-analytic studies and clinical trials. The high prevalence of CAD in the sample determined a higher PPV than NPV. It is concluded that, in Sergipe, CCTA has significant accuracy for the diagnosis of CAD, being recommended for the assessment of chest pain in patients at intermediate risk for CAD. 108672 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM People with Previous Covid Positive Diagnose Have Higher Pulse Wave Values and Their Hemodynamic Parameters of Arterial Stiffness? SARA CRISTINE MARQUES DOS SANTOS1, Luan Tardem Veloso Teixeira1, Thais Lemos de Souza Macedo1, Joao Pedro de Resende Cortes1, Ivan Lucas Picone Borges dos Anjos1, Paula Pitta de Resende Cortes1, Joao Carlos de Souza Cortes Junior1, Eduardo Tavares de Lima Trajano1, Carlos Eduardo Cardoso1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: In COVID infection, vascular stiffening may be induced due to indirect damage caused by the virus and its systemic inflammatory state and binding to angiotensin-converting enzyme 2, which cause cellular injury1. These mechanisms may contribute to the progression of atherosclerosis and increased cardiovascular risk, arterial stiffness, and augmentation index in previously infected individuals. The objective of the present study was to seek correlation between pulse wave analysis data in individuals up to 30 years of age who tested positive for COVID at least 15 days before the exam and individuals who were not infected. Methodology: Observational and cross-sectional study, carried out from May to July 2021 in students aged over 20 and under 30 years, in accordance with the current hypertension guideline of the Brazilian Society of Cardiology. Of 59 participants, 4 were excluded for absence of answers about COVID infection and 10 for age >30 years. After selection, participants were divided into 2 groups: prior COVID (CoP) and non-infected (NI). We used an anonymous questionnaire and the values provided by the Arteris device by means of the oscillometric method: PWV, AIX@75, heart rate (HR), central systolic pressure (CSBP) and central diastolic pressure (CDBP). The mean, maximum and minimum values were calculated using Excel software. Evaluation of sample normality (Shapiro-Wilk) and unpaired Student's T test (with Welch correction) were performed for parametric samples and Mann Whitney for non-parametric samples, with confidence level of 95% through GraphPad Prism Software version 9.2. Results: In the CoP group, the means were: PWV 4.65 m/s (5.4 +- 4.2); AIX@75 23.22% (40.7 +- 9.3); HR 89.5 bpm (119 +- 71); CSBP 97.72 mmHg (118 +- 80); CDBP 76.68 mmHg (98 +- 61). While in the NI group, the means were: PWV 4.58 mmHg (5.2 +- 3.1); AIX@75 21.85% (41.7 +- 5.3); HR 86.3 bpm (128 +- 60); CSBP 97.6 mmHg (113 +- 80) and CDBP 73.8 mmHg (54 +- 91). There was no statistical difference between PWV (p = 0.95) and AIX@75 (p = 0.63) values between CoP and NI group. Conclusion: Although higher values were observed for the CoP group in several hemodynamic and arterial stiffness parameters, no statistical difference was obtained between this group and NI group. However, it is valid to emphasize the importance of further studies in the area to be able to affirm or rule out the influence of the SARS-COV-2 virus on vascular integrity. 108678 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Assessment of Pain in Patients Submitted to Conventional Valve Replacement Surgery Versus Minimally Invasive Cardiac Surgery ARTHUR MAROT DE PAIVA2, Gabriel Baeta Branquinho Reis2, Luiz Fernando Sposito Ribeiro Baltazar2, Pedro Guimaraes Moreira da Silva2, Thais Vieira de Araujo Rodrigues1, Lays de Souza Albuquerque Oliveira1, Abissay Francisco Dias1, Marcos Vinicius Pires Rodrigues1, Joao Alberto Pansani1, Mauricio Lopes Prudente1, Artur Henrique de Souza1, Giulliano Gardenghi1 (1) Hospital ENCORE - Aparecida de Goiania/GO; (2) Universidade Federal de /GO Introduction: Minimally invasive cardiac surgery has becoming popular in the last two decades, associated with a better aesthetic effect and less surgical trauma, which may be related to a lower prevalence of pain or a different neuropathic component in pain. Objective: The aim is to compare the prevalence of pain in the first postoperative day (PO1) of patients undergoing valve replacement between conventional and minimally invasive techniques. Methods: Analytical cross-sectional study with patients undergoing heart valve replacement surgery between January 2020 and February 2022. Pain assessment was performed on the PO1 using the Visual Analog Pain Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) Scale. For the analysis of independent samples, the t-student test was performed with 5% significance. Results: 41 patients were included in the study. 33 patients underwent conventional heart valve replacement surgery (CONV group) and 8 patients underwent minimally invasive valve replacement surgery (MINI group). The mean age of the CONV group was 55.5 +- 12.5 years versus the MINI group: 62.9 +- 16.1 years (p = 0.19). Regarding pain intensity by VAS, the mean of the CONV group was 4.3 +- 3.4 points versus 4.1 +- 3.4 of the MINI group (p = 0.89). Regarding the number of painful areas, the CONV group had a mean of 1.3 +- 1.0 points versus 1.1 +- 0.8 of the MINI group (p = 0.59). In the CONV group, the main painful area was the sternal region and in the MINI group it was in the right thoracic region. According to the LANNS Scale in the CONV group, 72.7% of the patients had a score lower than 12, 15.2% did not report pain and could not be classified with the scale, and 12.1% had a score higher than 12. In the MINI group, 75% of patients scored less than 12 and 25% reported no pain, which means that no one in this group had a neuropathic pain. In the statistical analysis, there was no significant difference between the groups (p = 0.81). Conclusion: There was no difference between conventional and minimally invasive surgeries in terms of pain assessed in the present sample. 108683 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Prevalence of Delirium in Patients Undergoing Conventional Heart Valve Replacement Versus Minimally Invasive Cardiac Surgery ARTHUR MAROT DE PAIVA2, Gabriel Baeta Branquinho Reis2, Luiz Fernando Sposito Ribeiro Baltazar2, Pedro Guimaraes Moreira da Silva2, Thais Vieira de Araujo Rodrigues1, Abissay Francisco Dias1, Marcos Vinicius Pires Rodrigues1, Thaina Lopes de Souza1, Walace Chaves dos Santos1, Joao Alberto Pansani1, Artur Henrique de Souza1, Giulliano Gardenghi1 (1) Hospital ENCORE - Aparecida de Goiania/GO; (2) Universidade Federal de /GO Introduction: Minimally invasive cardiac surgery has been gaining popularity in the last two decades, associated with better aesthetic effect and decreased surgical trauma. Objective: The present study aims to compare patients undergoing valve replacement between conventional method and minimally invasive cardiac surgeries. Methods: Analytical cross-sectional study with patients undergoing heart valve replacement surgery between January 2020 and February 2022. Patients undergoing microsurgery were included from September 2021 onwards. The assessment of delirium was performed at first postoperative (PO1) day in an Intensive Care Unit (ICU) using the CAM-ICU and RASS scales. The evaluation of epidemiological data, previous comorbidities, use of pre and postoperative medications, anthropometric measurements and information related to the surgery were collected from TASY(r) electronic medical record system. The collected data were tabulated and calculated directly using specific spreadsheets with Excel 2010(r). For the analysis of independent samples, the t-student test was performed. Results: 41 patients were included in the study. 33 patients underwent heart valve replacement surgery by the conventional manner (CONV group) and 8 patients underwent minimally invasive cardiac surgery (MINI group). When comparing patients undergoing different surgical procedures, the mean age of patients in CONV group was 55.5 (+-12.5) and in MINI group was 62.9 (+-16.1) (p = 0.19). The mean BMI of CONV was 26.6 (+-3.8) and of MINI 27.7 (+-6) (p = 0.51). The mean of cardiopulmonary bypass (CPB) time in CONV was 99.2 (+-19.8) minutes and the mean clamping time was 71 (+-15.7) minutes and the mean CPB time of MINI was 115.4 (+-32.8) minutes (p = 0.08) and the mean clamping time was 76.9 (+-30.2) (p = 0.45). The mean number of comorbidities in CONV was 3.1 (+-2) and in MINI was 3.9 (+-2.5) (p = 0.33). In CONV, the mean of home medications was 4.1 (+-2.3) and in the postoperative period was 7.7(+-2.3), while in MINI the mean of home medications was 5.1(+-2, 9) (p = 0.29) and of postoperative medications was 7.1 (+-1) (p = 0.47). The overall incidence of delirium in the CONV was 15.2% and 12.5% in MINI (p = 0.85). Conclusions: The observed delirium prevalence findings were consistent with the current literature in both groups. Risk factors and triggers classically related to delirium, such as age and polypharmacy, was not statistically significant between the two groups. 108694 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Impact of . Off-Hours Admission of Patients with Stemi in Treatment and Hospital Outcomes in a Public University Hospital JARBAS RYGOLL DE OLIVEIRA FILHO1, ALESSANDRO MENEGHETTI ANVERSA2, ISABELLA KLAFKE BRIXNER3, ANDRESSA DUARTE SEEHABER3, NATALIA DA SILVEIRA COLISSI3, ALESSANDRA REBELATTO BOESING3, MATHEUS WERLANG DONADEL3, BRUNA SANTI DOS SANTOS3, ALEXANDRA SEIDE CARDOSO3, ALEXANDRE SHAAN DE QUADROS3, MATEUS DINIZ MARQUES3, ANIBAL PEREIRA ABELIN3 (1) Universidade Federal da Fronteira Sul (UFFS), Campus Passo Fundo, BRASIL; (2) Instituto de Cardiologia do RS/FUC, Porto Alegre, RS, BRASIL; (3) UFSM, Santa Maria, RS, BRASIL Background: ST-elevation myocardial infarction (STEMI) is a myocardial injury characterized by coronary artery occlusion. Treatment is rapid myocardial reperfusion performed through primary percutaneous coronary intervention (pPCI) or fibrinolytic therapy. Off-hours hospital presentation may impact the choice of reperfusion strategy, therefore increase cardiovascular outcomes. Objeticve: The aim of this study was to compare the effect of different times of presentation ( off-hours) on reperfusion strategy and in-hospital outcomes. Methods: Prospective cohort study, including patients diagnosed with STEMI between September/2016 and February/2020 in a public university hospital in southern Brazil. Patients were divided into off-hours admission. Off-hours presentation was defined as hospital admission between 18:00 p.m. and 8:00 a.m. from Monday to Friday and weekends. In-hospital outcomes were evaluated. Results: A total of 150 patients (56%) were admitted during off-hours, and 118 (44%) during on-hours. Baseline characteristics were balanced between the two groups, except that hypertension was more prevalent in the off-hour group. Patients admitted off-hours had a higher rate of non-reperfusion strategy (31.3% vs 22.9%), lower rate of fibrinolytic therapy (9.3% vs 22%) and similar pPCI (p = 0,011). Median door-to-balloon time was similar between groups (on-hours group: 119 min (IQR 56-175) vs. 109 min (IQR 59-161)) (p = 0,640). No difference was found in the rates of in-hospital mortality (p = 0,621) and MACCE (p = 0,16). Conclusions: In our hospital we observed a difference in the reperfusion estrategy between patients admitted on and off-hours, with a higher rate of non-reperfusion. However, there was no difference in-hospital outcomes. 109405 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 and Chronic Cardiovascular Diseases: Clinical and Epidemiological Indicators in Elderly People in Southern Brazil JARBAS RYGOLL DE OLIVEIRA FILHO1, EVA BRENDA SANTOS SILVA1, THIAGO EMANUEL RODRIGUES NOVAES1, TASSO KFURI ARAUJO MAFRA1, JOSSIMARA POLETTINI1, GUSTAVO OLSZANSKI ACRANI1, SHANA GINAR DA SILVA1, RENATA DOS SANTOS RABELLO1, IVANA LORAINE LINDEMANN1 (1) Universidade Federal da Fronteira Sul (UFFS), Campus Passo Fundo, BRASIL Introduction: The new viral infection, caused by Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2), called Coronavirus Disease 2019 (COVID-19), presents different clinical conditions and levels of severity, like patients who develop Acute Respiratory Syndrome. Severe (SRAG). Such cases are mostly elderly, considered at risk because they are more vulnerable due to physiological changes inherent to the aging process. Objectives: To identify the prevalence of hospitalization in the Intensive Care Unit (ICU), use of ventilatory support and case evolution in elderly patients diagnosed with COVID-19, carriers and non-carriers of chronic cardiovascular diseases (CVD). Methods: Observational study based on data analysis from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) in Passo Fundo, RS. The study population consisted of SARS cases due to COVID-19, confirmed and notified from January 1 to December 31, 2020. Sociodemographic and health data were collected from individuals aged 60 years or older. The use of ventilatory support, admission to the ICU and the evolution of the case (death/cure) were used as outcomes of interest, and the exposure analyzed was the diagnosis of CVD. The prevalence was verified with a 95% confidence interval (95%CI) of the outcomes and their distribution according to the predictor variable (chi-square test, admitting an a error of 5%). Results: The sample consisted of 585 participants, most of them women (52.3%), aged up to 75 years (63.4%) and with CVD (59.0%). Of the total, 31.4% were admitted to the ICU (CI95 28-35), 74.2% used ventilatory support (CI95 71-78) and 41.2% (CI95 37-46) died. A higher prevalence of ICU admission was observed among patients with CVD (34.3%, p = 0.031), but no statistically significant difference was identified in the relationship between CVD and death (38.0%, p = 0.242) and use of ventilatory support (75.5%, p = 0.320). Conclusions: Elderly people diagnosed with SARS by COVID-19, carriers of CVD, were more exposed to ICU admission, which reinforces that having CVD increases the complexity of the case. Although the mechanisms are not yet fully understood, it is possible that the fact is related to the action of the angiotensin-converting enzyme 2, the main gateway of SARS-COV2 in the body and also the target of treatments in patients with CVD. With regard to lethality and use of ventilatory support, it was not possible to establish a relationship. 108707 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Diseases in Teachers of the Public Education: Prevalence of Risk Factors JARBAS RYGOLL DE OLIVEIRA FILHO1, SILVIO LUIZ SIMOES ANCINES FILHO1, SABRINE AGUIAR DE SOUZA1, ALAN ROBSON FERREIRA DA PAZ JUNIOR1, GUSTAVO OLSZANSKI ACRANI1 (1) Universidade Federal da Fronteira Sul (UFFS), Campus Passo Fundo, BRASIL. Introduction: The relationship between risk factors (RF) for Cardiovascular Diseases (CVD) and patients workplace represents an important environmental factor. The Brazilian high school teacher is part of one of the classes that suffers most from environmental factors, occupying the second category of professionals with the highest presence of occupational diseases by the International Labour Organization (ILO). Objective: To analyze the prevalence of risk factors for cardiovascular disease among teachers of basic education in public schools in the city of Passo Fundo-RS-Brazil as well as the variables related to the outcome. Methods: This is a cross-sectional study, whose data were collected between August 2019 and February 2020 through a questionnaire sent to teachers by email and messages in mobile phone social network groups. Sociodemographic, life, health and employment data were collected. Cardiovascular risk stratification was calculated from the Brazilian Guidelines on Arterial Hypertension published by the Brazilian Society of Cardiology update 2020. Results: The sample consisted of 225 teachers, 91.1% women, 64.9% over 40 years old, 89.3% white, 54.5% with monthly income below R$ 5,000, 52.8% with more than 16 years of career, 73.4% with more than 30 working hours per week. After the analysis, it was found that 32% of those surveyed have a high risk for cardiovascular comorbidities in 10 years. It was possible to verify a statistically significant relationship between the presence of high cardiovascular risk among male teachers (60%, p = 0.005), age over 60 years (71.4%, p = 0.013), obesity (44%, p = 0.001), anxiety (37.5%, p = 0.018), RSI/WRMD (45.6%, p = 0.001) and exhaustion (42.9%, p = 0.044). Conclusions: The present study showed a high number of professors at high risk for cardiovascular disease in 10 years. It also found high rates of associated risk factors that denote negligence in the management of health care programs for teachers. The continuity in the production of studies on the relationship between teaching work and cardiovascular risk is fundamental for the development of measures that are, in fact, effective in combating the disease process, avoiding further complications in the future. 108709 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Influence of Blood Pressure Self Measurement on Pressure Control, Self-Medication and Emergency Visit GABRIELA DE OLIVEIRA SALAZAR1, Glessiane de Oliveira Almeida1, Felipe J Aidar1, Marcos Antonio Almeida-Santos1, Ikaro Daniel de Carvalho Barreto1, Dihogo Gama de Matos1, Claudia Bispo Martins-Santos1, Jose Icaro Nunes Cruz1, Joselina Luzia Menezes Oliveira2, Enaldo Vieira de Melo1, Jose Augusto Soares Barreto Filho2, Antonio Carlos Sobral Sousa2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital Introduction: One of the strategies to control hypertension, recommended by some guidelines, is the self-measurement of blood pressure (BP). However, the benefits of this practice are not yet unanimous. Objective: To assess whether there is an association between non-standardized BP self-measurement and the control of systemic arterial hypertension (SAH), self-medication and emergency department visit. Methodology: Observational, analytical and cross-sectional study. Information was obtained through a standardized questionnaire and medical records of patients seen at cardiology outpatient clinics in Sergipe (Brazil). Adults with SAH were included. BP was considered controlled when systolic and diastolic pressure did not exceed 130 mmHg and 80 mmHg, respectively. The Shapiro Wilk, Chi-square with odds ratio and the Mann-Whitney U tests were performed. A two-tailed p <= 0.05 was set for statistical significance. Results: The sample consisted of 1000 patients, with a mean age of 61 +- 12.5 years, 57.1% were women and 52.3% had comorbidities. Most (93.8%) used a digital device for self-measurement and 21.1% were aware of the need for annual calibration of the device, which was performed in 10.7% of the total. The highest frequency of self-measurement in the population was 1 to 3 times/day (35%). The symptom that most induced BP self-measurement was headache (44.4%; p < 0.0001). The most prevalent behaviors after verifying high BP were doing nothing (49.9%) and self-medication (26%), followed by looking for urgency and trying to contact the doctor (22.8% and 1.3%). 99.2% reported that there was no guidance on how to measure BP. There was no association between sex or age with BP self-measurement. Patients with comorbidities perform more self-assessment (p = 0.005), including diabetics, dyslipidemic patients, patients with obstructive arterial disease (p < 0.001) and stroke (p = 0.010). Self-measurement was associated with uncontrolled BP (p < 0.001; OR 1.953; 95% CI 1.707-2.233), emergency visits in the last 12 months for hypertensive causes (p < 0.001; OR 3.410; 95%CI 2.928-3.972) and to self-medication (p < 0.001; OR 1.958; 95% CI 1.703-2.251). Conclusion: Non-guided BP self-measurement, practiced by 93.8% of the sample, was associated with non-control of SAH, self-medication and more visits to the emergency department in the last 12 months. 108711 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Law No 12.732/12 and Analysis of Data Regarding the Time Interval between Diagnosis and Treatment of Malignant Neoplasm of the Heart, Mediastinum and Pleura in Brazil from 2019 to 2021 AUREA NATHALLIA GOMES DE SOUZA1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa UNIFAP Introduction: In 2012, law no 12.732/12 was approved in Brazil, which provides for the first treatment of patients with proven malignant neoplasia and establishes a maximum period of 60 days from the diagnosis as the start date. Objective: To analyze the data about the year of diagnosis and year of treatment, observing compliance with law no 12.732/12 in force in Brazil and other related aspects. Method: Were used the data available in PAINEL-ONCOLOGY, from the Department of Informatics of the Unified Health System (DATA-SUS), for more detail, in the detailed diagnosis category, C-38 (Malignant neoplasm of the heart, mediastinum and pleura), year of treatment and year of diagnosis and for a deeper analysis, the filters Month/Year of diagnosis and Month/Year of treatment were used, combining them and generating tables for analysis. Results: It is important to highlight the absence of data registered in the Information System over the years analyzed. Of the patients who were diagnosed in 2019, there is no information about the year of treatment for about 52.36%. Those who received their diagnosis in 2020 and 2021, the numbers also exceeded 50% of patients, being, respectively, 51.76% and 53.84%, approximately. In addition, some data were filled in incorrectly, stating that the patient started treatment one month before being diagnosed. Using the filter Month/Year of diagnosis and Month/Year of treatment, it can be said that law no 12,732/12 is complied with in most of the registered cases, but it was observed that in some cases there is a delay in starting treatment, overloading the subsequent months. The annual general data show that 26 people who were diagnosed in 2019 started their treatment in 2020, and when looking at the detailed data per month, only 8 were registered according to the month, of these, 5 in the period governed by the law. And 20 people diagnosed in 2020 started treatment in 2021, but in the detailed data per month, there is information about 4, and 3 started in the period governed by the law. There is no detailed information about the year 2021. Conclusion: The analysis was hampered by the lack of data, which also has an impact on the absence of public policies aimed at the delay in starting the treatment of malignant neoplasms in general, which can have negative consequences for the prognosis of patients. The records show partial compliance with Law no 12.732/12. 108721 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Factors Predicting Blood Pressure Control between Public and Private System Patients GABRIELA DE OLIVEIRA SALAZAR1, Glessiane de Oliveira Almeida1, Felipe J Aidar1, Marcos Antonio Almeida-Santos1, Ikaro Daniel de Carvalho Barreto1, Dihogo Gama de Matos1, Jose Icaro Nunes Cruz1, Claudia Bispo Martins-Santos1, Joselina Luzia Menezes Oliveira2, Jose Augusto Soares Barreto Filho2, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital Introduction: The number of hypertensive people in the world has doubled to 1.28 billion since 1990. It is estimated that about 50% of hypertensive people are uncontrolled. Objectives: To assess whether there are differences between the public and private systems in terms of blood pressure control and which factors predict non-control of systemic arterial hypertension (SAH) in these groups. Methods: Observational, cross-sectional and analytical study including hypertensive patients treated at cardiology outpatient clinics of the Unified Health System (SUS) and the Supplementary Network (RS) in Sergipe (Brazil). Information was obtained using a standardized questionnaire and medical records. The Shapiro Wilk, Chi-square, Mann-Whitney U test and binary logistic regression (backward stepwise method) were performed, which considered the model entry a p <= 0.25 and permanence <= 0.05. Results: Of the total, 50% of the patients were from the UHS and 50% from the SN. UHS users were more diabetic (24.6% vs. 18.6%; p = 0.021) and dyslipidemic (42.6% vs. 25.4% p < 0.001). UHS patients had more uncontrolled SAH, more visits to the emergency room in the last 12 months due to hypertension and fewer regular consultations with the cardiologist, while SN patients performed more self-medication. There was no difference regarding the self-measurement of blood pressure (BP). The predictors of uncontrolled SAH in both groups were emergency visits for hypertension and BP self-measurement. In the UHS, there were other factors, such as female sex and self-medication (Tables 1 and 2). Conclusion: There was a higher prevalence of uncontrolled SAH in the UHS, with female sex and self-medication being predictors of uncontrolled BP in this group, and self-measurement and emergency room visits predictors in both groups. 108727 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Increase in Cases of Arterial Hypertension in Childhood: An Overview of the Last Decade PRISCILA SANTOS MARIANO1, Amanda Cyntia Lima Fonseca Rodrigues2, Isabelly Salgado Marin3, Heloisa Belinati Pereira Perez3, Maria Carolina Casagrande3 (1) Universidade Federal de Ouro Preto; (2) Deutsche Hochdruckliga e.V. DHL(r) Deutsche Gesellschaft fur Hypertonie und Pravention; (3) Centro Universitario Inga Background and Aims: Arterial hypertension (AH) has become a common childhood health condition. When compared to adulthood, screening for childhood AH is complicated and unstable. This stems from the misunderstanding of the effects of AH in childhood, due to the scarcity of information about the long-term consequences of this condition, proof of this is that many pediatric patients have altered blood pressure and are not diagnosed or treated. Based on this evidence, there is a need for in-depth studies about primary hypertension in childhood and how its diagnosis and treatment can act in the prevention of cardiovascular diseases in adult life. Methods: This systematic review used the "PubMed" database to search for the descriptors "Arterial Hypertension" and "Childhood", associated with articles from the last 10 years, finding 122 articles, which 38 were selected to perform the abstract. Results: The prevalence of AH in the age group from 7 to 17 years remained stable, ranging from 4.4 to 6.4%. However, the risks of developing SAH increased considerably from 6.3% in 1995 to 19.2% in 2014, among the predisposing factors obesity stands out. In other analyses, other possible predisposing factors to childhood obesity, such as longitudinal effects of maternal depression, unhealthy lifestyle, high screen time and low levels of physical activity. In addition, it can also be mentioned that newborns of women with greater weight gain in the first trimester of pregnancy had an increased risk of overweight or obesity, as well as elevations in diastolic blood pressure. Children born to mothers who had gestational diabetes mellitus had significantly higher systolic and diastolic blood pressure. Conclusion: Childhood hypertension is becoming progressively more common in the pediatric population, which demonstrates an enormous public health challenge worldwide. There is a correlation between BMI and AH level in overweight adolescents, and the obese BMI range in this age group is related to an increased risk of incidence of cardiovascular diseases, morbidity (ischemic heart disease and stroke) and mortality in adulthood. Early identification of abnormal AH at young ages is of utmost importance, as it is possible to increase its control and awareness, in addition to reducing progression to higher levels of AH and target organ damage. 108852 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Clinical Outcome of Patients with Rheumatic Tricuspid Valve Disease: Matched Cohort Study IGOR MARQUES JORDAO1, Alana Helen Dos Santos Matos1, Ana Beatriz Cordeiro Prates1, Beatriz Dias Pinheiro1, Andre Barbosa de Andrade1, Isadora Goncalves Roque1, Lucas Lopes Toledo1, Isabel Pellegrinelli Bacelar1, Fernando Coletti Mazarao1, Jose Luiz Padilha da Silva2, William Antonio de Magalhaes Esteves1, Maria do Carmo Pereira Nunes1 (1) Federal University of Minas Gerais (UFMG); (2) Federal University of Parana (UFPR) Background: Rheumatic heart disease (RHD) is still a major health problem, especially in mid-income countries, leading premature deaths owing to valvular disease (VD). Although left-sided valvular involvement is most commonly seen in RHD, the tricuspid valve can also be affected. However, there is a lack of information about the prognostic value of primary tricuspid valve disease (TVD) in RHD. Objective: This study aimed to determine the impact of TVD on clinical outcome in RHD. Methods: This prospective study enrolled patients with RHD referred to a tertiary center in Brazil for management of VD between 2011 and 2021. Primary rheumatic TVD was defined by echocardiographic features including thickening of leaflets associated with some degree of restricted mobility. Patients with rheumatic TVD were matched to patients with mitral valve disease (MVD) using 1:1 genetic matching algorithm that maximized balance of baseline covariates prior to exploring outcome differences. The main outcome was either need for MV replacement or death. Results: Among 694 patients eligible for the study, age of 47 +- 13 years, 84% female, 39 patients (5.6%) had rheumatic TVD. After excluding patients with incomplete data, 33 patients with TVD were matched to 33 controls based on age, right-sided heart failure, atrial fibrillation, and MV area. Over a median follow-up of 28 months [interquartile range: 8-71], 28 underwent MV replacement, and 6 patients died. Kaplan-Meier survival estimates showed worse event-free survival in patients with TVD compared to matched controls . TVD was predictor of adverse events with a hazard ratio of 3.39 (95% CI: 1.56, 7.35, p = 0.002) in the genetic matched cohort with balance on baseline covariates of interest. Conclusions: In the setting of RHD, rheumatic TVD significantly increased risk of adverse events compared with matched controls. The involvement of TV may express overall disease severity that adversely affects clinical outcome. Our study is the first to assess clinical outcome using genetic matching approach to account for baseline differences in patients characteristics. 108743 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Takotsubo Cardiomyopathy and the COVID-19 Vaccine: A Systematic Review JESSICA SILVA ROCHA1, Gabriel Silva Rocha2, Andre Moises de Oliveira Nunes4, Geovanna Vitoria da Cruz Xavier Silva1, Julia Ranielly Oliveira Rios1, Lucas de Lacerda Ramos3 (1) Centro Universitario UniFTC (UniFTC); (2) Hospital Ana Nery (HAN); (3) Universidade Federal da Bahia (UFBA); (4) Escola Bahiana de Medicina e Saude Publica (EBMSP) Introduction: Takotsubo cardiomyopathy (TCM) is caused by catecholamine surge, which is also observed in COVID-19 disease due to cytokine storm. TCM refers to a transient left ventricular systolic dysfunction, usually with associated chest pain, whose main differential diagnosis is acute coronary syndromes. Although vaccination against SARS-CoV-2 is the primary factor in combating the pandemic, myocarditis has been demonstrated in reports as a side effect of the vaccine. And, despite being rare cases, a new category is being reported, with studies still limited, such as TCM. Objectives: To evaluate the association between the incidence of TCM and vaccination against the COVID-19 virus, in addition to characterizing the rate of post-vaccination TCM hospitalizations. Methods: This is a systematic review, in which the databases available on the platforms Pubmed, Lilacs, Medline were analyzed. For this, studies that address Takotsubo Syndrome related to COVID-19 vaccination were selected, following the PRISMA guidelines. As for the inclusion criteria, it consists of case reports presenting TCM as the only differential diagnosis, published in the last 2 years and available in the electronic version. The excluded studies were those that showed distance from the central objective of the research and duplication. Results: Seven eligible studies were selected for data collection. Of the results obtained, the female sex predominated (85.75%), mean age 62.1 +- 17.8 years, the mean number of days from the vaccine to the event was 3 days and 71.4% of the cases had some comorbidity. Conclusion: Typical epidemiological characteristics of Takotsubo Syndrome were evidenced, such as female gender, advanced age and the presence of comorbidities, in which the event was exclusively related to COVID-19 vaccination, subjectively excluding other causes. Therefore, the need for further studies characterizing TTK, as well as its relationship with mRNA vaccines is important, since there are also previous reports correlating TTK with the influenza vaccine. And from that, to evaluate the safety of mRNA vaccines and optimize patient outcomes. 108748 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Electrocardiographic Findings and Medical History of Female Soccer Professional Athletes GIULIA VITORIA NASCIMENTO DA SILVA1, LARISSA DACIER LOBATO COMESANHA2, TEREZA MARIA MEIRELES FERNANDES DA SILVA1, MARIANA DOS SANTOS GUIMARAES2, GABRIEL REZENDE NEVES1, MIGUEL CHAMOSO GILSANZ NETO1, PAULO CESAR LOBATO MAGALHAES2, GABRIELA DE ARRUDA CUSTODIO3, HENRIQUE CUSTODIO DA SILVA1 (1) Universidade do Estado do Para (UEPA); (2) Universidade Federal do Para (UFPA); (3) Centro Universitario Metropolitano da Amazonia (UNIFAMAZ) Introduction: Professional athletes constantly suffer physiological and anatomic alterations in the cardiovascular system in order to balance the intense cardiac activity during exercises. Although women develop less cardiac diseases in their life as a result of healthier habits of life than men, feminine athletes are not exempt from the constant cardiovascular adaptation inherent to high performance sports and its risks. In this regard, changes in the stimulant complex of the heart and in its structure may lead to some severe complications such as arrhythmias and cardiac insufficiency. Objective: To identify electrocardiographic abnormalities in athletes from a professional women's soccer team. Method: Cross-sectional, analytical-descriptive and quantitative study. Data were obtained through medical records of 20 professional female soccer athletes, in the year 2020, in the city of Belem, Brazil. In addition to electrocardiographic records, information on age, family history, chest pain when practicing physical activity and consumption of alcohol drinks were also analyzed. Chi-square test and Fisher's exact test were used for statistical analysis of variables. Results: The average age of the athletes were 25.1 +- 3.9 years. In the study population, only 4 participants (20%) had ECG abnormalities, which were 2 right bundle branch conduction delay (50%), 1 left ventricular hypertrophy signs (25%) and 1 right bundle branch block (25%,). There was no statistical significance between alcohol consumption and the presence or absence of ECG changes (p > 0.05). Moreover, there were also no statistically significant differences associated with ECG changes when related to the presence of chest pain during physical activity or the existence of a family history of sudden death or heart disease (p > 0.05). Conclusion: The findings of the present study showed electrocardiogram abnormalities in 20% of the athletes included, but not related to chest pain, family history of sudden death or heart disease, nor to the use of alcohol drinks, being in similarity with other studies available in the literature. Despite this, the importance of continuity of cardiological medical evaluation by athletes for the prevention of cardiovascular diseases and possible sudden death is highlighted. 108756 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Malaria Increases Blood Pressure and Risk of Hypertension in an Observational Study in the Brazilian Amazon KARINE OLIVEIRA LIMA1, Laura Cordeiro Gomes2, Philip Brainin3, Marliton Vinicius Pedrosa Evangelista1, Isabelle Victoria Martins Vieira1, Anna Engell Holm3, Luan Oliveira Matos1, Bianca Vasconcellos Rodrigues Lopes4, Iara Fernanda Vasconcelos de Oliveira e Silva1, Tor Bierning-Sorensen5, Claudio Romero Farias Marinho2, Odilson Marcos Silvestre5 (1) Multidisciplinary Center, Federal University of Acre, Campus Floresta, Cruzeiro do Sul, Acre, Brazil; (2) Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; (3) Department of Cardiology, Herlev-Gentofte University Hospital, Hellerup, Denmark; (4) Health and Sport Science Center, Federal University of Acre, Rio Branco, Acre, Brazil; (5) Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark Background: The prevalence of hypertension in malaria endemic areas seems to be higher than in malaria-free areas. In these regions, a higher rate of hypertension has been detected in younger people when compared to developed countries. We aimed to investigate the relationship between malaria episodes and hypertension in the Brazilian Amazon. Methods: The study was conducted in the Brazilian Western Amazon from June 2020 to August 2021. Patients with a lifetime history of malaria, but not infected at inclusion had a cross-sectional assessment. However, those who were infected with Plasmodium spp. at enrollment (T0) had a follow-up evaluation (FUP) performed 34 +- 7.2 days later. All of them answered a questionnaire concerning clinical and sociodemographic information and underwent physical examination. Patients were classified as hypertensive through previous medical diagnosis and/or according to the International Society of Hypertension parameters: >=140 systolic blood pressure (SBP) and/or >=90 diastolic blood pressure (DBP). The mean between both arms were considered for SBP and DBP. Since variables were non-parametric, Wilcoxon signed-rank test was applied to compare blood pressure betweenT0 and FUP. Logistic regression was performed to assess the risk of hypertension as a function of the age at the first malaria episode. Results: Seventy-six symptomatic malaria patients completed the follow-up evaluation. The median age was 37 years (IQR 26 to 48) and 59% were males. A significant increase in the SBP (median [IQR] T0 119.5 mmHg [.5] vs FUP 122.5 mmHg [113.75-134], P = 0.015) and DBP (median [IQR] T0 74.5 mmHg [68-82.75] vs FUP 77.5 mmHg [72.5-84], P < 0.001) was found in the follow-up when compared to enrollment. Additionally, a total of 430 patients were included in the cross-sectional study [53% males; median age 39 years (IQR 30 to 47)]. Median age of the first malaria episode was 17 (IQR 12 to 27) years. After adjusting for number of previous malaria episodes, age, abdominal circumference, income, sex, smoking and diabetes, age at first malaria infection was associated with higher risk of hypertension [Odds ratio 1.031 (95% CI 1.006 to 1.057), P = 0.014]. Conclusion: Age at the first malaria episode seems to influence blood pressure levels. Both SBP and DBP increased 34 days after infection. More studies to investigate this association are required to improve health policies on hypertension in communities living in malaria endemic areas. 109436 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Physical Exertion and Emotions as Triggers of Stroke: A Systematic Review JOAO PEDRO TORRES NEIVA RODRIGUES1, Raquel Vieira Torres1, Pedro Viana Diniz1 (1) Universidade Federal de Juiz de Fora Introduction: Risk factors for stroke onset are well known. However, factors that may act as a trigger still need clarification. Objective: We aimed to review data from the literature to assess the role of physical exertion or emotional distress as triggers of stroke. Methods: Reviewers researched on Pubmed, Embase, and PsycINFO for cohort, case-control, or case-crossover studies with exposition to triggers within 3 months of stroke onset. PRISMA protocol was used. Results: 323 articles were found, and after applying inclusion criteria, 17 studies remained. Combined, there were 1168152 cases of stroke. Physical exertion was defined in most articles as activities that require more than 5 METs to be performed, however, sexual activity, and lifting >23 kg, were also included. Eight studies analyzed this group, and 5 studies reported a correlation between physical exertion and the onset of stroke. 15 studies reported emotional triggers such as anger, psychological distress, startling, positive, and negative emotions were investigated. A correlation between emotions and the onset of stroke was found in 12 studies (Table 1). Different cutoffs were used to determine an emotional outburst, which could increase studies heterogeneity and could cause discordant results between them. Self-reported questionnaires can be prone to memory bias. Conclusion: Physical exertion and emotional triggers were associated with an increased risk of stroke onset in most studies. 108793 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION Automatic Detection of Heart Diseases on Electrocardiograms using Machine Learning GUSTAVO SANTOS PORFIRO1, Gustavo Santos Porfiro1, Leonardo Favaro Pereira1, Rosemberg Rodrigues Dal Gobbo1, Fernando Luiz Torres Gomes1 (1) Universidade Federal do Espirito Santo; (2) Universidade Federal do Espirito Santo; (3) Universidade Federal do Espirito Santo; (4) Universidade Federal do Espirito Santo; (5) Universidade Federal do Espirito Santo; (6) Universidade Federal do Espirito Santo Introduction: Heart diseases are the leading cause of death in the world, affecting developed and underdeveloped countries, and have been presenting progressive and alarming growth. Early diagnosis of this type of condition is fundamental to reduce mortality. The main and most common way of diagnosing heart disease is the electrocardiogram (ECG), which is totally dependent on the supervision of a specialized professional. Consequently, it is pertinent to observe the need for preventive diagnosis in order to minimize the high mortality rates of these diseases. Objective: To investigate the selection and prediction of Machine Learning (ML) algorithms to facilitate the process of identifying heart diseases from electrocardiogram signals. Methods: We conducted a literature review, covering the period from January 2021 to January 2022, in the Pubmed, Cochrane and Physionet databases. The descriptors "machine learning", "heart diseases", "electrocardiogram", separated by Boolean operators AND, were searched in the Medical Subject Heading. Among the inclusion criteria were full-text articles published from 2011 onwards. Results: Performance evaluation of an ML algorithm was performed by means of statistical metrics relating overall prediction hit rate, accuracy and the confusion matrix to the treatment of tabular data. It was obtained from algorithms and solutions with open source code a hit rate higher than 80% both in predicting normal ECG exams and in predicting classes that presented heart disorders, such as myocardial infarction, being that in some cases the hit rates were higher than 75% for normal exams and almost 90% in relation to exams with myocardial infarction. Conclusion: The use of intelligent software based on Machine Learning to facilitate the diagnosis of heart diseases is a promising advance, given the alarming growth of these diseases according to data from the World Health Organization. With increasingly advanced technology and improved resources, this software can partially reduce the dependence on analysis by a professional, and can indicate findings that may be overlooked by professionals. It is, then, an ally to the professionals who deal with these types of exams, and not their substitutes. 108798 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Analysis of the Indication for Coronary Computed Tomography Angiography in Patients with Known or Suspected Coronary Artery Disease in a Particular Diagnostic Imaging Center in Curitiba CAROLINA DOS ANJOS BASTOS1, Carolina dos Anjos Bastos1, Eduardo Pires dos Santos1, Anderson Rafael Pesamosca1, Tania Zaleski1, Wilton Francisco Gomes1 (1) Faculdades Pequeno Principe (FPP) Background: Cardiovascular diseases (CVD) remain the leading cause of premature death worldwide. There are several diagnostic methods for its detection, among them coronary computed tomography angiography (CTA), with increasing use in recent years. Defining the most appropriate complementary test, in terms of accuracy for clinical decision making and rationalization of resources, remains a challenge in medical practice. Objective: To analyze the appropriateness of the indications for CTA in a sample from a private clinic in Curitiba, taking as reference the II Guidelines for Cardiovascular Magnetic Resonance and Computed Tomography of the Brazilian Society of Cardiology and Brazilian College of Radiology (IIDRT) and the Roll of the National Agency for Supplementary Health (ANS). As a secondary objective, to analyze the main variables that correlated with the presence of obstructive CAD in this sample. Method: This is an observational and retrospective study, with the analysis of 2595 consecutive CTA exams for the evaluation of CAD, between January 2019 and December 2020. Indications were classified according to IIDRT recommendation classes and ANS Roll recommendations. Multivariate analysis was used for correlation between independent variables and outcome. Results: Regarding the IIDRT indications for the performance of CTA, 1170 (45.1%) individuals fit into recommendation class I, 10 (0.4%) into IIa, 175 (6.7%) into IIb, 550 (21.2%) into III and 690 (26.6%) did not fit into any expected indication. As for the ANS Roll, 1620 (62.4%) individuals fit the indication criteria, while 975 (37.6%) did not. Risk factors such as dyslipidemia, diabetes and family medical history were associated with obstructive CAD in CTA (p < 0.001). Conclusion: 47.8% of patients referred for CTA had a class III recommendation or did not have indications according to the IIDRT. By ANS criteria, over 37.6% of patients had non-predicted indications. This denotes that a critical analysis of current recommendations as well as clinical practice should probably be performed. 108803 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERIOPERATIVE EVALUATION Infections in the Postoperative Period of Cardiac Surgery: Incidence, Mortality and Hospitalization Time EDUARDO PORTO SANTOS1, RAFAEL FORTES LOCATELI1, ANNA CAROLINA FLORES MARIATH2, VITORIA CAROLINA KOHLRAUSCH1, ISABELLA KLAFKE BRIXNER1, GABRIELLE LENZ DE ABREU2, ANIBAL PEREIRA ABELIN1, DIEGO CHEMELLO1, MATEUS DINIZ MARQUES1 (1) UNIVERSIDADE FEDERAL DE SANTA MARIA; (2) HOSPITAL UNIVERSITARIO DE SANTA MARIA Background: Infection is the most frequent non-cardiac complication after cardiac surgery. Its incidence is associated with increased mortality, hospitalization days and costs. Objective: The aim of this study is to describe the incidence of infections in patients undergoing cardiac surgery at the University Hospital of Santa Maria and hospitalization days and mortality associated with. Methods: This is a descriptive, longitudinal and retrospective study analyzing the medical records of patients undergoing cardiac surgery between September 2018 and April 2021. Patients undergoing pacemaker implantation or pericardial surgery or those who died intraoperatively were excluded. The analysis was performed using the software Stata version 15.1, and the results were expressed as percentage, mean and standard deviation. Results: From a database of 200 patients, 194 filled the inclusion criteria. Of these, 60 patients (30.92%) were diagnosed with infection and used antibiotics postoperatively and 16 died (26.67%). The mortality among patients without nfection was 6.0% (8 patients). Infection was associated with death during hospitalization (x2 = 16.37; p < 0.001), with 66.67% of deaths occurring among patients with infection. individuals with infection had higher mean hospitalization days than those without infection using the Mann Whitney U test (20 +- 15 days and 9 +- 5 days, respectively, U = 1465.500, Z = -7.099, p < 00.1). Conclusions: The study portrayed the reality of a tertiary public hospital for heart surgery in the countryside, with a high incidence of postoperative infection. The diagnosis of infection was associated with longer hospital stay and higher mortality. The factors associated with higher incidence of infection and management factors need to be addressed in detail in future studies. 108808 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Female Sex is a Protective Factor Against Coronary Artery Disease JOSE ICARO NUNES CRUZ1, Claudia Bispo Martins-Santos1, Gabriela de Oliveira Salazar1, Juliana Maria Chianca Lira1, Mayara Evelyn Gomes Lopes1, Ana Luisa Lisboa Prado1, Marilia Marques Aquino1, Nathalia Luiza Silva Sobral1, Arthur Leite Lessa1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or - Sao Lucas Hospital Introduction: Cardiovascular diseases are important causes of morbidity and mortality worldwide. Among these, coronary artery disease (CAD) stands out as a significant cause of death and health costs. Some studies demonstrated that female sex is a protective factor for CAD in the premenopausal period, suggesting a beneficial action of endogenous estrogens on the heart. In this context, it is essential to analyze the risk factors and prevalence of CAD between the sexes. Objectives: To assess the frequency of CAD, as well as its characteristics, according to sex. Methods: This is an observational, cross-sectional, analytical study. The sample included patients who underwent coronary computed tomography angiography (CCTA) in a private hospital. Coronary stenosis >= 50% was considered significant on CCTA. Statistical analysis was conducted using Chi-Square test, with significance level set at 5% for comparisons. Odds ratio (OR) and 95% confidence intervals (CI95%) were also described. All analyses were performed using SPSS Statistics software, version 22.0. Results: The sample consisted of 1250 patients, of which 48.3% (604) were female. The mean age was 57.9 +- 12.9 years, with a non-significant difference between the sexes (p > 0.05). Women demonstrated higher frequencies of obesity (27.9% vs. 21.8%; p = 0.027) and sedentary lifestyle (75.3% vs. 65.3%; p = 0.001). Men demonstrated higher rates of smoking (4.6% vs. 3.8%; p = 0.041) and alcohol consumption (41.2% vs. 18.0%; p < 0.001). Male subjects exhibited higher prevalence of CAD (52.6% vs. 38.1%; p < 0.001), as well as higher chance of calcified plaques (OR: 1.95; CI95%: 1.40-2.72; p < 0.001) and non-calcified plaques (OR: 1.75; CI95%: 1.08-2.82; p = 0.021). In addition, men were more likely to have significant coronary stenosis (OR: 2.65; CI95%: 1.82-3.85; p < 0.001), as well as triple vessel CAD (OR: 3.88; CI95%: 2.02-7.46; p < 0.001) and double vessel CAD (OR: 2.76; CI95%: 1.72-4.43; p < 0.001). Conclusions: The prevalence of CAD was lower among women. Men were more likely to have calcified and non-calcified plaques, significant coronary stenosis, double vessel CAD and triple vessel CAD. Thus, it is concluded that females are less affected by CAD. 108817 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Alcohol Consumption and Cardiorespiratory Fitness in Echocardiogram Evaluated Women Under Physical Stress GABRIELA DE OLIVEIRA SALAZAR1, Jose Icaro Nunes Cruz1, Claudia Bispo Martins-Santos1, Juliana Maria Chianca Lira1, Lucas Villar Shan de Carvalho Cardoso1, Nathalia Luiza Silva Sobral1, Ana Luisa Lisboa Prado1, Giulia Vieira Santos1, Mayara Evelyn Gomes Lopes1, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa2, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Lucas Hospital Introduction: Low cardiorespiratory fitness (CF) is a risk factor for cardiovascular morbidity and mortality. Women have significantly lower CFs than men. Furthermore, alcohol consumption is a known determinant of disease burden, although there is still no consensus on the influence of alcohol on CF. In recent years there has been an increase in alcohol consumption among women. Objective: To identify predictors of low CF in women, with emphasis on the influence of social alcohol consumption on CF. Methods: Observational, cross-sectional, analytical study, with data collection from record of echocardiogram exams under physical stress performed in Sergipe (Brazil). Female patients were included. The CF was classified according to the metabolic equivalent of task (MET) as low (MET < 7.9), intermediate (7.9 <= MET < 10.9) and high (MET >= 10.9). Statistical analysis included the chi-square test and multinomial logistic regression using SPSS Statistics software. A value of 5% was set for statistical significance. Results: 2202 patients were included, with a mean age of 58.48 +- 10.9 years. Among the risk factors, 54.1% were hypertensive, 47.5% sedentary, 46.4% dyslipidemic, 21.9% obese, 17.1% alcoholic and 4.3% smokers. CF was considered low in 35%, intermediate in 37.5% and high in 27.5% of the population studied. Alcohol consumption was a predictor of low CF in women, compared to those with high and intermediate CF, as well as sedentary lifestyle. Systemic arterial hypertension (SAH) and obesity predicted low CF when compared to the high CF group (Table 1). Conclusion: Alcohol consumption was an independent predictor associated with low CF in women. The same was verified with the presence of sedentary lifestyle, SAH and obesity. 108835 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Assessment of Left Ventricular Dysfunction using Native T1 Mapping Through Cardiac Magnetic Resonance Imaging JOSE ICARO NUNES CRUZ1, Gabriela de Oliveira Salazar1, Claudia Bispo Martins-Santos1, Lara Teles Alencar Duarte1, Nathalia Luiza Silva Sobral1, Juliana Maria Chianca Lira1, Raisan Almeida Santos2, Myllena Maria Santos Santana1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2, Luiz Flavio Galvao Goncalves2 (1) Federal University of Sergipe; (2) Rede D'Or - Sao Lucas Hospital Introduction: The pathophysiology of ventricular dysfunction comprises cardiac remodeling with formation of diffuse cardiac fibrosis, a marker of poor prognosis. Native T1 mapping, performed by cardiac magnetic resonance imaging (CMRI), is a non-invasive method of assessing compromised myocardial areas, such as fibrotic areas, being considered a sensitive marker of cardiovascular morbidity and mortality. Objectives: To associate native T1 mapping with parameters related to left ventricular dysfunction on CMRI. Methods: This is an observational, cross-sectional, analytical study. The sample included patients who underwent CMRI in a Phillips Ingenia 1.5T magnet, from a private hospital located in Sergipe (Brazil), in 2021. Native T1 mapping of the left ventricle was compared with other variables related to ventricular function, which were indexed to body surface when measurements were borderline. Statistical analysis was performed using the Mann-Whitney U test and one-way analysis of variance (ANOVA) adjusted by bootstrapping, followed by Games-Howell post-hoc. All analyses were performed using SPSS Statistics software, version 22.0. Results: Among 415 patients who underwent CMRI in 2021, native T1 mapping was originally obtained for 225 patients (54.2%). The median native T1 mapping in the included sample was 1036 ms (IQR: 1008.0-1067.0 ms). Native T1 mapping values were significantly higher in patients with increased left ventricular (LV) end-diastolic volume (1055.5 vs. 1035.0 ms; p = 0.003), increased LV mass (1066.5 vs. 1034.0 ms; p < 0.001) and increased left atrium (LA) size (1053.0 vs. 1033.0 ms; p < 0.001). The native T1 mapping was also superior in patients with reduced left ventricular ejection fraction (LVEF) compared to patients with preserved LVEF (1143.53 vs. 1032.03 ms; p = 0.001), as well as among patients with LVEF borderline compared to those with preserved LVEF (1077.35 vs. 1032.03 ms; p = 0.007). Conclusions: Elevated native T1 mapping was strongly associated with indicators of cardiac dysfunction, such as greater LV end-diastolic volume, greater LV mass, greater LA dimension and reduced LVEF. Thus, the study confirms the applicability of native T1 mapping on the assessment of heart failure. 108857 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Metabolically Healthy Obesity in a Young Population Assisted by the Family Health Strategy ANA RACHEL BUCAR CERVASIO1, Clara Avelar Mendes Vasconcellos1, Carlos Augusto Parente Macedo Moura1, Daniel Barreto Kendler1, Deisianny Santos Ferreira1, Elizabeth Silaid Muxfeldt1, Karine da Silva Guimaraes1, Gabriela Gama Zagni Jardim1, Livia Lopes Monteiro de Barros Junqueira1, Rodney Barbera Boghossian1, Tomas de Souza Mello1, Vitoria Santa Marinha Flumignan1 (1) IDOMED - Universidade Estacio de Sa, Medicine School, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil - UNESA Background: Obesity is increasing in younger populations, and is associated with a high cardiovascular (CV) risk, however, it is not clear whether metabolically healthy obesity (MHO) may have a lower CV risk or if it is just an earlier stage of the disease. Objective: To evaluate the prevalence and cardiovascular (CV) risk factors associated with metabolically healthy obesity (MHO) in a young population assisted by a Family Health Care unit in a large urban center. Design and Methods: A cross-sectional population study for CV risk assessment in adults aged 20-50 years old from a Family Health Care unit. Demographic, anthropometric data and CV risk factors were recorded. All underwent office blood pressure (BP) measurements, laboratory evaluation (lipid and glycidic profile). Obesity was defined as a body mass index (BMI) > 30 kg/m2 and MHO are those who have less than 3 of the following criteria for metabolic syndrome: office BP higher or equal to 130 x 85 mmHg, hypertension, fasting blood sugar higher or equal to 100 mg/dL, HDL < 40 mg/dL (men) and 50 mg/dL (women), triglycerides >150 mg/dL and waist circumference > 102 cm (men) and > 88 cm (women). Results: A total of 632 individuals were evaluated (60% female; mean age 37 +- 9 years). The prevalence of obesity was 26%, of which 73% were classified as MHO. Obeses are older, with a higher prevalence of physical inactivity (51% vs 41%, p = 0.03), hypertension (44% vs 19%, p < 0.001), dyslipidemia (50% vs 36%, p = 0.002), and diabetes (7% vs 2%, p = 0.001) with higher systolic OBP. MHO compared to unhealthy ones are significantly younger and smoke less. Despite being obese, they have lower BMI (33.6 vs 35.2 kg/m2, p = 0.02) and abdominal circumference (102 vs 110 cm, p = 0.03), with lower diastolic BP. Conclusion: MHO was more prevalent in this young population and seems to have a lower CV risk, however it is not clear whether these younger and less obese individuals are only at an earlier stage of the disease. Perhaps the CV diseases onset is postponed for a few years. Even so, these individuals should not be excluded from public health policies as a form of primary prevention. 108872 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Kidney Subclinical Lesions in Hypertension Phenotypes Defined by Home Blood Pressure Monitoring Among Young Adults Enrolled in a Family Health Strategy Unit CLARA AVELAR MENDES DE VASCONCELLOS1, Tomas de Souza Mello1, Karine da Silva Guimaraes1, Gabriela Gama Zagni Jardim1, Ana Rachel Bucar Cervasio1, Carlos Augusto Parente Macedo Moura1, Felipe Rey Costa Tostes1, Pedro Henrique dos Santos Lemos1, Clara Maria da Costa Muguet1, Joana Sauerbronn Correa da Costa1, Inah Maria Drummond Pecly1, Elizabeth Silaid Muxfeldt1 (1) IDOMED - Universidade Estacio de Sa, School of Medicine, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil. Introduction: The association between kidney lesion, hypertension (HTN) and cardiovascular risk (CV) is well established. Asymptomatic patients with decreased glomerular filtration rate (GFR) and/or increased albuminuria seem to have increased CV risk. The refinement of HTN diagnosis using Home Blood Pressure Monitoring (HBPM) allows to identify individuals with different phenotypes: normotension, sustained HTN, masked HTN and white-coat HTN, increasing diagnostic accuracy. Objective: To assess kidney subclinical lesions among different HTN phenotypes identified by HBPM in an adult population enrolled in a Family Health Strategy unit. Design and Methods: Cross-sectional, populational study with adults between 20-50 years old enrolled in a Family Health Strategy unit in a metropolis. Sociodemographic, anthropometric and CV risk factors were registered. Office blood pressure (BP) was the average of two consecutive measurements, and HBPM followed a 7-day protocol. HBPM < 135 x 85 mmHg and office BP < 140 x 90 mmHg were considered normal, identifying four phenotypes: normotension (controlled office BP and HBPM); white-coat HTN (uncontrolled office BP and controlled HBPM); masked HTN (controlled office BP and uncontrolled HBPM) and sustained HTN (uncontrolled office BP and HBPM). Albuminuria was dosed in an isolated urine sample whereas GFR was calculated by CKD Epi formula using serum creatinine. Results: 483 individuals were evaluated (39% male; mean age: 37.6 +- 8.8 years). More often, individuals with white-coat HTN (9.3%) are male, with greater neck circumference and higher prevalence of metabolic syndrome. Individuals with masked HTN (10%) are more obese, with increased neck and waist circumferences whereas those who present sustained HTN are predominantly male, more obese, with increased neck and waist circumferences and higher prevalence of diabetes and metabolic syndrome. Analyzing four phenotypes, a progressive albuminuria increase was observed among normotensive patients: white-coat HTN 4.0 +- 2.2; masked HTN 5.3 +- 3.4 and sustained HTN 7.1 +- 1.4 mg/g creatinine. We also observed an increased serum creatinine and decreased GFR: white-coat HTN 0.74 +- 0.16/132 +- 34; masked HTN 0.79 +- 0.17/123 +- 28; sustained HTN 0.81 +- 0.32/120 +- 59, respectively, although without statistical significance. Conclusion: The performance of HBPM refined HTN diagnosis and was able to early identify a progressive worsening of kidney function parameters in the different phenotypes. 110530 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Medication Adherence Rate of Apparent Resistant Hypertensive Patients in a Teaching-Care Outpatient Clinic GABRIELA FREITAS VALVERDE 1, Gabriel Martins Nogueira1, Bruna Marmori Lima1, Joao Victor Araujo de Oliveira1, Adriana Santiago de Carvalho Borges1, Lorena de Souza Santos1, Gabriel Von Flach Sarmento1, Alexandra Brito Rocha da Silva1, Jessica Reis de Jesus1, Ana Flavia de Souza Moura1, Constanca Margarida Sampaio Cruz2 (1) Escola Bahiana de Medicina e Saude Publica (EBMSP); (2) Obras Sociais Irma Dulce (OSID) Introduction: Resistant Arterial Hypertension (RHTN) is a clinical condition in which blood pressure (BP) remains above target even with the concomitant use of three specific antihypertensive drugs of different classes at maximum doses or within the target using 4 or more of those. The main factor interfering with BP control is drug non-adherence, which can be assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8), an update of the four-item, still not widely found in national studies on RHTN. Thus, this study aims to estimate the rate of medication adherence in patients with apparent RHTN and correlated factors in a teaching-care outpatient clinic. Methods: This is a cross-sectional study carried of patients treated at a cardiology teaching-care outpatient clinic, over 18 years old, diagnosed with hypertension and with at least six months of antihypertensive treatment. Patients with severe psychiatric and/or cognitive limitations, who did not meet RHTN criteria and with secondary hypertension were excluded from the sample. Medication adherence was collected through the application of the MMAS-8 questionnaire in person, in an outpatient clinic and by telepresence, through a virtual form. The score obtained for the therapeutic adherence rate ranges from zero to eight, with eight considered high adherence, >= 6 and < 8, medium adherence and < 6, low adherence. Results: A total of 31 patients were included in the study, 23 (74.19%) women and a median age of 60 (IQR 53-65) years. Furthermore, 18 (58.06%) had a family history of hypertension, 20 (64.5%) had no BP control, 25 (80.64%) were sedentary, nine (29.03%) were alcoholics and the most prevalent comorbidity was Diabetes Mellitus (35.4%). The body mass index (BMI) was, on average, 32.37 (IQR 27.10-35.86), the median time of diagnosis of hypertension was 10 (IQR 4-15.5) years and the median number of antihypertensive drugs in use and the median total number of drugs were four (IQR 3-4.5) and seven (IQR 5-8.5), respectively. The median score obtained on the MMAS-8 was 5.75 (IQR 4.75-7.75), considered low adherence. It was found that the no BP control (p = 0.020), a higher BMI (p = 0.043) and higher serum urea values (p = 0.045) are correlated with a lower rate of adherence to antihypertensive drugs. Conclusion: Low outpatient medication adherence to antihypertensive drugs was found. There was a correlation between adherence and the control variables of BP, BMI and serum urea values. 108904 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Negative Correlation of Coronary Artery Disease in Patients with Chagas Disease: A Case-Control Study FRANCISCO JEAN DE MOURA SANTOS FILHO1, Carlos Eduardo Batista de Lima1, Andre Goncalves Honorio Carvalho1, Maria Clara Lima Almeida2, Paulo Marcio de Sousa Nunes1, Antonio Maycon da Silva Sousa1, Patryck Araujo Dantas1, Mauro Guimaraes Albuquerque1, Ginivaldo Victor Ribeiro do Nascimento1, Francisco Cesar de Oliveira Goncalves1, Arthur Oliveira Nogueira e Lago1, Jardel Silva Santos3 (1) Hospital Universitario da Universidade Federal do Piaui (HU-UFPI) - Empresa Brasileira de Servicos Hospitalares (EBSERH); (2) Instituto do Coracao do Hospital das Clinicas da Universidade de Sao Paulo - InCor HCFMUSP; (3) Universidade Estadual do Piaui (UESPI) - Hospital Getulio Vargas (HGV) Introduction: Chagas cardiomyopathy is a myocarditis that can progress to dilated non-ischemic cardiomyopathy, heart failure, ventricular arrhythmias and thromboembolic complications. During the chronic phase, an important proportion of patients complain of atypical chest pain. Some studies showed a lower occurrence of chronic coronary disease in Chagas disease, but this fact is not clarified. Objective: Comparative analysis of structural cardiac alterations and the presence of severe obstructive coronary artery disease in patients with and without Chagas disease. Methods: A paired case-control study for atherosclerosis risk factors based on the Framingham risk score (FRS). From November 2014 to November 2019, all patients undergoing coronary angiography at the University Hospital of the Federal University of Piaui, in an elective basis for investigation of coronary disease, were evaluated and chagasic patients were selected, confirmed with two positive serological tests by different methods. The control group was selected consecutively in a 1:3 ratio. For statistical analysis, the chi-square test was used, considering the value of p < 0.05 for statistical significance. Results: Among 1120 patients evaluated, 15 patients with Chagas disease were identified and 45 patients without a diagnosis of Chagas disease were selected. The FRS variables, including age, sex, arterial hypertension, diabetes, physical inactivity, smoking, dyslipidemia and ejection fraction showed no statistical difference between the groups. The occurrence rate of CAD was lower in chagasic patients: 13.3% versus 64.4%, and for severe CAD the percentages were 13.3% and 51.1% (p = 0.003). The presence of structural cardiac alterations was high in both groups, being 80% of the chagasic and 73.3% of the non-chagasic, with no statistical difference (p = 0.606). Conclusion: In this series, the presence of segmental structural alterations of the left ventricle was high in both groups, while in the evaluation of coronary artery disease there was a lower occurrence in the group of patients with Chagas disease. 108910 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Correlation between Remote Myocardial T1 Mapping with Morphological and Functional Parameters in Patients with Chronic Infarction GABRIELA DE OLIVEIRA SALAZAR1, Claudia Bispo Martins-Santos1, Jose Icaro Nunes Cruz1, Lara Teles Alencar Duarte1, Nathalia Luiza Silva Sobral1, Juliana Maria Chianca Lira1, Mayara Evelyn Gomes Lopes1, Raisan Almeida Santos2, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa2, Joselina Luzia Menezes Oliveira2, Luiz Flavio Galvao Goncalves2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Lucas Hospital Introduction: Risk stratification in patients with chronic infarction is based on left ventricular (LV) morphological and functional parameters, such as left ventricular ejection fraction (LVEF), left ventricular volumes, extent of delayed gadolinium enhancement, among others risk scores. However, native T1 and extracellular volume (ECV), tools for the assessment of interstitial fibrosis, when measured in the myocardium distant from the infarcted territory, present an association of poor prognosis in patients with chronic infarction. Objective: To evaluate the correlation between native T1 and ECV with LV morphological and functional parameters in patients with chronic infarction. Methods: Observational, cross-sectional, analytical study. Patients who underwent cardiac magnetic resonance imaging using a Philips Ingenia 1.5T magnet in 2021 in Sergipe (Brazil) were included. Patients with delayed transmural and/or subendocardial enhancement compatible with myocardial infarction were selected and those with acute infarction or other diagnoses were excluded. T1 measurements were performed in myocardium without delayed enhancement using specific software, and ECV was calculated using native and post-contrast T1 of the myocardium and cavity, in addition to hematocrit. The analysis included the execution of the Shapiro-Wilk tests, Spearman correlation and Mann Whitney U test. The significance level was set at 5%. Results: Of the 75 patients with delayed subendocardial or transmural enhancement, 56 (74.7%) had chronic infarction. The mean age was 68.14 +- 10.24 years. The mean value of native T1 was 1044 +- 43 ms and ECV was 29.8% +- 4.7. There was a negative correlation between T1 and LVEF (r-0.374; p = 0.027). The group with increased T1, considering local reference value (>1030 ms), had a higher LV systolic diameter (Md 47.2 vs. 40.2; p = 0.049; TDE-LC 69.4%) and lower LVEF (Md 43 vs. 58; p = 0.038; TDE-LC 70.4%). The group with increased ECV (ECV > 28%) had higher LV mass (Md 96 vs. 120; p = 0.019; TDE-LC 78.4%). Conclusion: The value of native T1 showed an inverse correlation with LVEF. The group with increased T1 had higher LV systolic diameters and lower LVEF. The group with increased ECV had higher LV mass. These findings suggest that the increase in T1 and ECV may be associated with LV remodeling, resulting in diffuse interstitial fibrosis, which may impact the long-term prognosis. 108914 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Inflammatory Biomarkers and Obesity in Resistant Hypertension GABRIELA DA SILVA NASCIMENTO1, Fernanda Oliveira de Carvalho Carlos1, Carlos Filipe dos Santos Pimenta1, Victor Margallo1, Joao Gabriell Bezerra da Silva1, Bianca Zattar de Mello Barreto1, Carolina de Carvalho Fortes1, Marcus Vinicius Serejo Borges Vale da Silva1, Sofia Luz Coutinho Botelho Lobo1, Arthur Fernandes Cortez1, Bernardo Chedier1, Elizabeth Silaid Muxfeldt1 (1) UFRJ, Universidade Federal do Rio de Janeiro - Faculdade de Medicina, Hospital Universitario Clementino Fraga Filho - ProHart Inflammatory: Biomarkers and Obesity in Resistant Hypertension Fundamental: In the last few years, obesity has acquired pandemic features, being an important public health's problem and being strongly related to cardiovascular diseases, beyond of being responsible for the difficulty of blood pressure and metabolic control of patients with resistant hypertension (RHT) apparently due to an inflammatory process that underlines this unfavorable context. Objective: To evaluate the relationship between inflammatory biomarkers and obesity in a large cohort of patients with RHT. Methods: This cross-sectional study evaluated 423 subjects with RHT (30.5% male; 63.9 +- 10.8 years old), 215 (50,8%) of whom are obese. In all subjects the inflammatory biomarkers, TNF-a, MCP-1, E-Selectin and PAI-1, were dosed. Socio-demographic characteristics, anthropometric measurements and cardiovascular risk factors were recorded. Variance analysis compared the serum levels of 4 biomarkers inflammatory and the bivariate analysis compared resistant hypertensives with and without obesity. Results: Obese subjects are younger, with a higher prevalence of peripheral obstructive arterial disease. No difference was found concerning to the blood pressure, neither to subclinical lesions. The values of PAI-1 (123 [107-164] vs 113 [89-138] and E-Selectin (53.2 [34.2-68.6] vs 44.6 [20.8-62.0] were significantly higher in patients with obesity. The other biomarkers evaluated did not evidence association with obesity. Conclusion: Among the inflammatory biomarkers evaluated, which was most strongly correlated with obesity was PAI-1 and E-Selectin. According to literature PAI-1 is tightly linked to metabolic disorders, such as insulin resistance and central obesity, while E-Selectin has an important role on atherosclerosis's development. 108916 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Effect of Long-Term use of Continuous Positive Airway Pressure Treatment on Arterial Stiffness in Patients with Obstructive Sleep Apnea and Resistant Hypertension CAMILA BELLO NEMER1, Bianca Zattar de Mello Barreto1, Carolina de Carvalho Fortes1, Marcus Vinicius Serejo Borges Vale da Silva1, Sofia Luz Coutinho Botelho Lobo1, Aline de Hollanda Cavalcanti1, Joao Carlos Moreno de Azevedo1, Carlos Filipe dos Santos Pimenta1, Taissa Lorena dos Santos1, Bernardo Chedier1, Elizabeth Silaid Muxfeldt1, Christian Nejm Roderjan1 (1) Universidade Federal do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho - ProHArt Objective: To evaluate the impact of a long-term use of CPAP on arterial stiffness (AS) measured by pulse wave velocity (PWV) in patients with resistant hypertension (RHT) and moderate-severe obstructive sleep apnea (OSA). Design and Methods: An observational prospective study was performed in 121 patients (38% male, mean age 60.7 +- 7.8 years) with RHT and moderate/severe OSA (AHI > 15/hour) divided in 2 groups using CPAP (CPAP group - n = 62) and not using CPAP (control group - n = 59) and followed for at least 12 months. Pulse wave velocityand ABPM were measured before and after follow-up. Primary outcomes were changes in aortic stiffness. Intergroup comparisons of differences in PWV were assessed by a general linear model with allocation group (CPAP or control) as a fixed factor and adjusted for their respective baseline PWV values in addition to gender, age, and 24-hour SBP values. Per-protocol analysis was performed excluding patients with poor CPAP adherence. Results: Patients were followed-up for a median of 68 [49-81] months. They used a median of 5 [3-8] anti-hypertensive drugs and had mean PWV of 8.41 +- 1.52 m/s. CPAP and control groups were similar in their baseline demographic, anthropometric, office and ambulatory BP, PWV, and laboratory characteristics. Control group had a mean increase in PWV of 0.88 m/s (95% CI: 0.52-1.25 m/s, p < 0.001), whereas CPAP group had an average increase in PWV of 1.20 m/s (95% CI: 0.84-1.55 m/s; p < 0.001). After adjustment for initial PWV, gender, age and 24-systolic BP, the mean difference between CPAP and control groups was +0.32 (95%CI: 0.17-0.83; p = 0.20). In a subgroup analysis with patients with higher PWV (>10 m/s) the mean difference adjusted was -0.20 (95%CI: -2.17-1.75, p = 0.83). Conclusions: Long-term treatment with CPAP did not reduce aortic stiffness in RHT with moderate/severe OSA, but it may prevent its worsening in relation to control group in those with baseline increased arterial stiffness. 108917 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERIOPERATIVE EVALUATION Incidence, Mortality and Hospitalization Time of Postoperative Atrial Fibrillation in Cardiac Surgery RAFAEL FORTES LOCATELI1, Vitoria Carolina Kohlrausch1, Eduardo Porto Santos1, Isabella Klafke Brixner1, Anna Carolina Flores Mariath2, Gabrielle Lenz de Abreu2, Anibal Pereira Abelin1, Diego Chemello1, Mateus Diniz Marques1 (1) Universidade Federal de Santa Maria - UFSM; (2) Hospital Universitario de Santa Maria - HUSM Introduction: Arrhythmias are one of the most frequent cardiac complications in the cardiac surgeries postoperative. Atrial fibrillation (AF) is the most common arrhythmia with 20 to 50% incidence. Most cases occur in the first five postoperative days, with a maximum incidence on the 2nd day. The consequences of AF are increased hospital stay, risk of recurrence and increased mortality. Objective: This study aims to compare mortality and hospital stay among patients who presented AF and those who did not have AF in the postoperative period of cardiac surgery at the University Hospital of Santa Maria from January 2011 to April 2021. Methods: This is a longitudinal, descriptive and retrospective study reviewing physical and electronic medical records of patients undergoing cardiac surgery at public tertiary hospital at Santa Maria, Brazil. Exclusion criteria are age younger than 18 years or a procedure involving only the pericardium or pacemaker implantation. The variables analyzed for this study were the occurrence of AF, period of occurrence and death during hospitalization. Results: From a database of 856 patients, 30,96% patients were diagnosed with AF in the postoperative period (n = 265). The mean number of days for the occurrence was 3,35 and the day with the highest incidence was the 2nd. The total number of deaths in the study was 82 (9,57%). Among those who had AF, the mortality was 7,54% (n = 20) and the odds ratio was 0,6965 (CI 95% 0,41-1,17; p = 0,08). The mean hospitalization days for those who had AF was 14 +- 13 days, and 10 +- 9 days for those without AF. Those without AF had lower hospitalization days (-3.57 days, CI 95% - 5.13 - -2; p < 0.0001). Conclusions: This analysis highlights the reality of a tertiary hospital in southern Brazil. AF occurrence was not associated with overall mortality during hospitalization despite a longer hospital stay. Data continues to be collected and future analyzes will show more accurate results. 108919 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERIOPERATIVE EVALUATION Incidence and Mortality of Stroke in the Postoperative Period of Cardiac Surgery in a Brazilian University Hospital VITORIA CAROLINA KOHLRAUSCH1, Vitoria Carolina Kohlrausch1, Rafael Fortes Locateli1, Eduardo Porto Santos1, Anna Carolina Flores Mariath2, Gabrielle Lenz de Abreu2, Anibal Pereira Abelin1, Diego Chemello1, Mateus Diniz Marques1 (1) Universidade Federal de Santa Maria - UFSM; (2) Hospital Universitario de Santa Maria - HUSM Introduction: Stroke in the cardiac surgery postoperative is an important neurologic complication. Postoperative stroke is defined as occurring up to 30 days after the procedure, with 56% of them occurring within the first 24 hours. The incidence usually varies between 1.3 to 5% of the procedures and the mortality is from 13 to 41%. Objective: The purpose of this study is to describe the incidence and mortality of stroke in the postoperative period of cardiac surgery at the University Hospital of Santa Maria from January 2011 to April 2021. Methods: The physical and electronic medical records of patients undergoing cardiac procedures at the HUSM were reviewed, between January 2011 and April 2021. This is a retrospective and longitudinal study. and pericardium or only pacemaker implantation procedures were not included. A total of 857 medical records were reviewed and the variables of stroke presentation in the postoperative period, time in days of stroke after surgery and death were evaluated. Data were analyzed using EpiInfo software (version 7.2.5.0.) and comparisons were made based on articles indexed in the PubMed platform. Results: Of the 857 patients included in the study, 3.73% had a stroke in the postoperative period (n = 32; SD = 2.66%-5.22%) - with 46.88% occurred in the first 24 hours after surgery (n = 15; SD = 29.09%-65.26%). The overall mortality was 9.57% (n = 82; SD = 7.78%-11.72%), and higher in the group with perioperative stroke (25%;n = 8; SD = 11.46%-43.40%) than in the group that did not develop this complication (8.97%; n = 74; SD = 7.21-11.11%), with OR = 3.3829, x2 = 9.13, p < 0,005. Conclusions: Despite the low income and economical barriers faced by public hospitals in Brazil we showed that a tertiary public hospital in southern Brazil has similar results than general hospitals around the world regarding neurologic complications in the cardiac surgery postoperative. The database continues to be filled and new studies are being written, analyzing variables such as sex, age and previous diseases. 108926 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Cardiovascular Risk and Subclinical Target Organ Damage in a Young Adult Population Provided by a Primary Healthcare Unit KARINE DA SILVA GUIMARAES1, Gabriela Gama Zagni Jardim1, Ana Rachel Bucar Cervasio1, Clara Avelar Mendes de Vasconcellos1, Tomas de Souza Mello1, Carlos Augusto Parente Macedo Moura1, Mariana Stutz Klen1, Heitor de Oliveira Moraes Rego Bandeira1, Diego Alves Calvao1, Ramon Narde Simao1, Ana Cristina Tenorio da Costa Fernandes1, Elizabeth Silaid Muxfeldt1 (1) IDOMED - Universidade Estacio de Sa, Medicine School, Campus Vista Carioca, Rio de Janeiro - RJ Background: In primary care it is necessary to identify early cardiovascular risk factors and target organ damage with low complexity procedures. The most available with low cost are Ankle-Brachial Index (ABI), left ventricular hypertrophy by voltage index in ECG and aortic stiffness by pulse pressure (PP) calculation. Objective: To evaluate cardiovascular risk factors and subclinical target organ damage in a young and apparently healthy population assisted in a Primary Healthcare unit. Design and Methods: A cross-sectional population study for cardiovascular risk assessment in adults aged 20-50 years old provided by a Primary Healthcare Unit. A total of 632 individuals were evaluated (40% male; mean age 36 +- 9 years). Sociodemographic, anthropometric data, and traditional cardiovascular risk factors were recorded. All underwent office Blood Pressure (BP) and pulse pressure (PP) (systolic BP minus diastolic BP) was calculated. Ankle-brachial index (ABI) was also calculated after BP measurements in the 4 limbs. The median of the ABI was 1.14 [1.08-1.22], which is the cutoff point used to define early changes. All participants were submitted to ECG to calculate Sokolow-Lyon Index (SLI) and Cornell Voltage Index (CVI) for left ventricular hypertrophy diagnosis. We considered the median of the SLI (20 mm) and the CVI (11 mm) as the cutoff point for early alterations. Results: The prevalence of hypertension was 16%. The median [IQR] office PP was 46 [39-52] mmHg. Elevated Office PP (> 60 mmHg) were identified in 64 participants. High office PP was more frequent in men, obese, with increased neck circumference and lower ABI (1.07 vs 1.16, p < 0.001). It was also associated with higher voltage index: SLI 21.9 vs 19.8, p = 0.04 and CVI 13.4 vs 7.1, p = 0.03. Individuals with decreased ABI are more obese with smaller neck circumference (10 vs 5%, p = 0.03). They also had higher systolic BP (125 vs 119 mmHg, p < 0.001) and PP (49 vs 43 mmHg, p < 0.001). A total of 362 ECGs were performed. Increased SLI was more frequent in men, younger and overweight, in addition to a higher prevalence of hypertension and higher PP. Those with increased CVI are more often male, obese with higher BP levels. Conclusion: In this young population, early changes in subclinical target organ damage already identify a higher cardiovascular risk profile, indicating the importance of implementing primary prevention measures to reduce this risk. 109374 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Effects of High Intensity Interval Training and Moderate Intensity Continuous Training on the Right Ventricle in Obese Women BRENDA BARETA SIRONI1, Wendell Arthur Lopes1, Caroline Ferraz Simoes1, Joao Carlos Locatelli1, Higor Barbosa Reck1, Victor Hugo de Souza Mendes1, Gustavo Henrique de Oliveira1, Rogerio Toshiro Passos Okawa1 (1) Universidade Estadual de Maringa Introduction: Obesity appears to affect the right ventricle, considered the forgotten chamber in cardiac evaluation. The TAPSE (tricuspid annular plane systolic excursion) have been used for this evaluation, and more recently, new methods of evaluating the right ventricle function have been developed, in which the right free wall Longitudinal Strain, and the FAC (fractional area change), are highlighted. Studies have shown that aerobic training seems to have some effects on the right ventricular structure and function, however little is known about the impact of different types of training on it. Objective: To investigate the effects of 8 weeks of HIIT (high intensity interval training) and MICT (moderate intensity continuous training) on right ventricle by three different methods (TAPSE, FAC and right strain) in obese women. Methods: The sample consisted of 44 women with obesity grade I or II (age: 28.4 +- 4.8 years; BMI: 35.6 +- 3.1 kg/m2), who were randomly allocated to the HIIT group (n = 22) and MICT (n = 22). The training protocols were adjusted so that both promoted similar energy expenditure. Echocardiographic measurements of left and right ventricular function and morphology were evaluated using the Vivid T8 GE ultrasound system. The Vo2 max, was measured during a cardiopulmonary stress testing, with the Cortex device. Body composition was measured using a tetrapolar bioimpedance device. Data were analyzed using the Statistical Package for the Social Sciences (SPSS, IBM(r)). Differences between the HIIT and MICT groups and moments before and after 8 weeks of training were explored by the ANOVA test for repeated measures. Results: Twenty-five obese women completed 8 weeks of HIIT (n = 11) or MICT (n = 14). Both HIIT and MICT training significantly increased the TAPSE (p = < 0.006; <0.026), FAC (p = 0.002; <0.001) and right free wall GLS (p = <0.003; <0.001). Only HIIT reduced body mass (p = 0.002), body mass index (p = 0.002), body fat percentage (BF% p = <0.001), and significantly increased VO2peak (p = 0.024.). Conclusion: The results obtained with 8 weeks of training on the right ventricle function showed no difference between the two exercise training interventions, both with a positive impact in the right ventricle function parameters. Overall, aerobic training can be considered as a potential intervention for substantial improvements in the right ventricle function of young women with grade I and II obesity, however, HIIT may have additional benefits. 108978 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Impact of Long-Term use of CPAP Treatment on Blood Pressure Among Refractory Hypertensive Patients with Obstructive Sleep Apnea CAROLINA DE CARVALHO FORTES1, Carolina de Carvalho Fortes1, Taissa Lorena Dos Santos1, Camila Bello Nemer1, Sofia Luz Coutinho Botelho Lobo1, Gabriela da Silva Nascimento1, Hugo Farah Affonso Alves1, Lucca Hiroshi de Sa Kimura1, Aline de Hollanda Cavalcanti1, Joao Carlos Moreno de Azevedo1, Bernardo Chedier1, Elizabeth Silaid Muxfeldt1 (1) Universidade Federal Do Rio de Janeiro - Hospital Universitario Clementino Fraga Filho - ProHArt Objective: To assess blood pressure response to long-term continuous positive airway pressure (CPAP) treatment among patients with refractory hypertension (RfHTN) with moderate and severe obstructive sleep apnea (OSA). Design and Methods: An observational prospective study was performed in 26 patients (35.7% male, average age 59.3 +- 7.9 years) with diagnostic of RfHTN and moderate and severe OSA who were divided in 2 groups to use CPAP (CPAP group, n = 13) or not (control group, n = 15). All of them were submitted to clinical follow-up and their anti-hypertensive medication was adjusted according to the assistant physician. 24-hour ABPM was performed both at the beginning and at the end of the study. Primary outcomes were changes in office and ambulatory blood pressure (BP) and BP control. The comparison between groups of BP changes were calculated by a general linear model with group allocation as a fixed factor and adjusted by its respective BP basal values in addition to gender and age. Results: The median follow-up time was 68 months (IQR: 49-81 months). CPAP and control groups were similar in their baseline demographic, anthropometric, laboratory characteristics, and office and ambulatory BP. They had mean systolic and diastolic 24-hour BP of 142 (15) and 83 (14), respectively. At the end of follow-up, refractory patients using CPAP had a reduction of 8.5 and 5.0 mmHg of office systolic and diastolic BP with an intergroup difference (CPAP and control) of 13.5 (-15.2-42.3) mmHg and 10.1 (-7.5-5.4) mmHg, respectively. The most important difference between groups was noticed at nighttime with an intergroup difference of 10.0 (-8.6-28.7) mmHg of systolic BP and 6.7 (-3.9-17.3) mmHg of nighttime diastolic BP. Out of 28 initial refractory patients, 12 are not refractory anymore, being 3 (20%) in control group and 9 (69.2%) in CPAP group with a significant difference between the groups (p = 0.02) Conclusion: Long-term use of CPAP among refractory hypertensive patients with moderate/severe OSA seems to be effective to reduce and control blood pressure measured both in the office BP and 24-hour ABPM, especially lowering nighttime blood pressure. 108960 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Factors, Lifestyle and Social Determinants in a Cross-Sectional Population Study GABRIELA GAMA ZAGNI JARDIM1, Ana Rachel Bucar Cervasio1, Clara Avelar Mendes de Vasconcellos1, Tomas de Souza Mello1, Karine da Silva Guimaraes1, Giovanna Francesca Ferreira Maselli1, Michelle Felipe Falcao1, Ivan da Costa Velho Junior1, Raphaella Ferrao1, Inah Maria Drummond Pecly1, Rafael Bica1, Elizabeth Silaid Muxfeldt1 (1) IDOMED - Universidade Estacio de Sa, Medicine School, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil. Objective: To evaluate the relationship between the main CV risk factors and socioeconomic indicators in a population of adults registered in a Family Health Care (FHC) unit in the center of Rio de Janeiro. Design and Methods: Cross-sectional population study that included adults aged between 20 and 50 years living in the area covered by the FHC in Rio de Janeiro. Demographic data (gender and age), socioeconomic data (education level, profession, employment), CV risk factors (smoking, sedentary lifestyle, obesity, hypertension, diabetes, dyslipidemia) were recorded. The metabolic profile is evaluated through laboratory tests. Those who studied up to high school were considered poorly educated. Results: 604 individuals were enrolled [39% male, mean age: 38.8 +- 8,9 years] The median of schooling was 12 years. 288 individuals had high schooling, 44.5% were male. A total of 130 individuals did not study or work. Women with low education had a higher risk of smoking, obesity and hypertension with no difference regarding labor or study activities. Otherwise, men with low education had higher risk of sedentary lifestyle and hypertension. Among men, not working or studying increased the risk of smoking and hypertension. Conclusion: We found an inverse association between socioeconomic conditions and the prevalence of CV risk factors. Women are more affected by low schooling, while men are more affected by their working occupation. The study suggests that socioeconomic factors influence the CV risk, affecting men and women differently, pointing to the need for public policies to reverse this situation. 109353 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Dizziness Complaints and Cardiorespiratory Fitness Post Severe Forms of COVID-19 Among the Middle-Aged Population GLORIA DE MORAES MARCHIORI1, Gloria de Moraes Marchiori1, Braulio Henrique Magnani Branco1, Mauricio Medeiros Lemos1, Daiane Soares de Almeida Ciquinato1, Elen Cristina Bressiano1, Luciana Lozza de Moraes Marchiori1 (1) Universidade UniCesumar UniCesumar Introduction: Dizziness is a common nonspecific sensation of disorientation or impairment in spatial perception and stability. The pathophysiology of post COVID-19 rotatory dizziness is probably similar to that of other viral infections, with some of its manifestations such as hypercoagulability and microthrombus formation, causing significant circulatory disorders possibly affecting its pathogenesis. Cardiorespiratory fitness is one of the significant variables to monitor health, and the gold standard used has been maximal or peak consumption of oxygen (VO2max or VO2peak) through a direct analysis of gas exchange. Thus, VO2max demonstrates the maximum capacity of an individual to absorb, transport, and consume oxygen fitness may be used to identify those at the most significant risk for severe COVID-19 illness. Association between dizziness complaints and cardiorespiratory fitness has not been investigated in individuals with severe forms of COVID-19. Objective: To verify whether there is a correlation between dizziness complaints and cardiorespiratory fitness among people with severe forms of COVID-19. Methods: This study presents a cross-sectional design part of a broader research named the "Post COVID-19 project." The human research ethics committee approved the project of the institution, with a sample of people post COVID-19 who responded to the Visual-Analog Scale (VAS) for dizziness. To evaluate cardiorespiratory fitness, it used the clinical assessment and Bruce test to measure oxygen consumption directly (via gas analyzer). Results: Of the 133 participants, with a mean age of 49.8 +- 12.2 years old. The prevalence of self-reported dizziness was 51.1% (n = 68); of these, 9.8% (n = 13) were related to dizziness prior to the diagnosis of COVID-19 and 41.4% (n = 55) were related to dizziness during or after COVID-19. The subgroup analysis for age groups, a difference was found in the middle-age (45-64 years) group for the absolute VO2 peak (p = 0.027). Conclusion: There was a statistically significant difference between dizziness complaints and the VO2 peak among the middle-aged population, with the dizziness group having a lower absolute VO2 peak than the non-dizziness group. 109001 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Comparative Study of Pulse Wave Analysis and Other Hemodynamic Parameters in Medical Students: Initial Data SARA CRISTINE MARQUES DOS SANTOS1, Luan Tardem Veloso Teixeira1, Ivan Lucas Picone Borges dos Anjos1, Thais Lemos de Souza Macedo1, Joao Pedro de Resende Cortes1, Paula Pitta de Resende Cortes1, Joao Carlos de Souza Cortes Junior1, Eduardo Tavares de Lima Trajano1, Carlos Eduardo Cardoso1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Pulse wave velocity is currently (PWV) considered a gold standard parameter in the assessment of arterial stiffness, and may be associated with cardiovascular risk in several groups. Stiffness is characterized by the decrease in arterial distensibility, being present in aging, diabetes, atherosclerosis and chronic renal disease1. The objective of the present study was to perform the analysis of central and peripheral hemodynamic values in men and women aged 30 years old or less. Methodology: Observational and cross-sectional study, carried out from May to July 2021 in students aged up to 30 years (in accordance with the first group for pulse wave velocity of the current brazilian hypertension guideline). 49 participants were selected, 32 female (F) and 17 male (M). It was used an anonymous questionnaire and the values provided by the Arteris device through the oscillometric method: PWV; AIX@75; heart rate (HR); peripheral systolic blood pressure (SBP) and central (CSBP); and peripheral diastolic (DBP) and central (CDBP); centre pulse pressure (CPP), cardiac output (CO); vascular age (VA); peripheral vascular resistance (SVR) and cardiac index (CI). For the general group (G) mean, maximum and minimum values were calculated; while for M and F, only the mean was calculated. Results: Mean age G was 23 years (29 +- 20), M 22 and F 23; PWV G of 4.65 m/s (5.4 +- 3.1), M 4.9 and F 4.5; AIX@75 G of 22.6% (41.7 +- 5.3), M 18.4% and F 25%; SBP G of 111 mmHg (137 +- 88), M 120 and F 107; DBP G 74.5 mmHg (96 +- 56), M 77 and F 73; CSPB G 98 mmHg (118 +- 80), M 103 and F 95; CDPB G 75.5 mmHg (98 +- 54), M 79 and F 73.5; HR G 88 bpm (128 +- 60), M 83 and F 90; CPP G 22 mmHg (36 +- 13), M 24.5 and F 20.5; VA G of 22.6 years (32 +- 18), M 25 and F 21; CO G 3.9 l/min (4.6 +- 2.9), M 4.1 and F 3.81; SVR G 1.30 mmHg/ml (1.58 +- 0.97), M 1.29 and F 1.30; CI G 3.9 l/min/m2 (4.6 +- 2.9), M 4.1 and F 3.8. Conclusion: Men presented higher values of PWV, SBP, DBP, CSPB, CDPB, CPP, VA, CO and CI both in relation to the female group and to the general group. Meanwhile, women obtained higher values in SVR, HR and AIX@75. It is worth noting that the values of CSPB and PWV found in the study participants are within the normal range for the population without cardiovascular risk factor (established in the 2020 hypertension guideline of the Brazilian Society of Cardiology) while they are borderline in the European index of CSPB and adequate for PWV. 109005 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Pulse Wave Analysis in a Group of Individuals with and Without Family History of Arterial Hypertension: Preliminary Data SARA CRISTINE MARQUES DOS SANTOS1, Luan Tardem Veloso Teixeira1, Joao Pedro de Resende Cortes1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Paula Pitta de Resende Cortes1, Joao Carlos de Souza Cortes Junior1, Eduardo Tavares de Lima Trajano1, Carlos Eduardo Cardoso1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Family history of hypertension (FHH) is a strong risk factor for the development of high blood pressure (HBP), where individuals of normotensive parents would have a lower occurrence of the stiffening process of the arteries1. It is believed that stiffness also has a genetic influence, as well as HBP and age2. The mechanism of pulse wave velocity (PWV) and HPB is not completely established; there is an increase in PWV with increased blood pressure, but it is still not possible to define which is the cause or consequence3. The objective of the present study was to analyze two groups: with positive family history of HBP (PFH) and the group with negative family history of HBP (NFH) through the answers of questionnaires about self-knowledge, life habits, the values provided by the Arteris device of central hemodynamics and arterial stiffness, such as PWV, AIX@75, central systolic pressure (CSP), central diastolic pressure (CDP), central pulse pressure (CPP) and vascular age (VA). Methodology: Observational, cross-sectional study conducted from May to July 2021 in medical students. Done through an anonymous questionnaire and analysis of the pulse wave by the oscillometric method in the Arteris device. The mean was calculated using Excel. Evaluation of sample normality (Shapiro-Wilk), multiple logistic regression, with confidence level of 95% and calculated odds ratio by GraphPad Prism Software version 9.2. Results: Total of 59 participants, mean age of 25.29 (20 +- 42), where 45 belonged to the PFH group and 14 to the NFH group. When analysing the values obtained by the device, the PFH group obtained averages of: PWV 4.82 m/s (6.6 +- 3.1); AIX@75 22.59% (41.67 +- 5.33); CSP 97.47 mmHg (124 +- 11); CDP 77.13 mmHg (106 +- 58); CPP 36.27 mmHg (61 +- 21) and VA 24.84 (45 +- 18). While in the NFH group, means of: PWV 4.76 m/s (5.4 +- 4.2); AIX@75 18.53% (37.67 +- 8.67); CSP 99.86 mmHg (118 +- 81); CDP 75.14 mmHg (98 +- 54); CPP 37.85 mmHg (52 +- 26) and VA 23.36 (32 +- 18). The lower the PWV, the lower the chance of having PFH (OR: 0.4) and the lower the CPP (OR = 0.7), CDP (OR = 0.9) and PWV (OR = 0.3); the lower the probability of being hypertensive. Conclusion: In the PFH group, the values of PWV, AIX@75, CDP and VA were higher than those found in those NFH. Also, it was possible to show statistically that the PFH can influence the increase in the value of PWV, the reduction of the levels of PWV and other hemodynamic parameters are important for prevention of HBP. 109013 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Diagnostic Value of Atherogenic Indices in Atherosclerotic Cardiovascular Diseases YURI BARBOSA ARAUJO1, Glebson Santos Sobral1, Rafael Alexandre Meneguz Moreno1 (1) Universidade Federal de Sergipe Background: For years, the search for clinically useful assessment methods with good accuracy, low cost, non-invasiveness and easy management has been stimulated, aiming to improve the prevention and treatment of atherosclerotic diseases. Objective: To verify the diagnostic potential of the following indices in patients with clinical Atherosclerotic Cardiovascular Disease (ASCVD): Castelli I and II indices, Atherogenic Coefficient, Atherogenic Index of Plasma (AIP) and the variation of the perfusion index between 90 and 120 seconds after reactive hyperemia in the evaluated limb (DPI90-120). Methods: A case-control study, of whom 161 patients were included so far, of which 44 (27.3%) were part of the ASCVD group, selected by means of a cinecoronariography, exercise stress test, coronary CTA, cranial CT, carotid or lower limb artery Doppler. To estimate the potential of these atherogenic indices, sensitivity, specificity, positive (PV+) and negative (PV-) predictive value, positive (LR+) and negative (LR-) likelihood ratios were estimated through receiver operating characteristic (ROC) curves. Additionally, multivariate logistic regression was performed to estimate the association of these indices with the outcome. Values of p < 0.05 were considered statistically significant. Results: The number of patients with a history of smoking, hypertension, diabetes mellitus and dyslipidemia was higher in the ASCVD group, as well as mean age and some laboratory parameters: HDL-c, triglycerides, HbA1c and creatinine. The ROC analysis showed better performance with AIP and DPI90-120. For the former, a cut-off of (> 0.04) achieved an LR+ and 4.84 and 0.15, respectively (sensitivity 88.0%; specificity 81.8%; PV+ 64.7%; .7%). For the latter, a cut-off of (<= 56.6) achieved an LR+ and 5.76 and 0.30, respectively (sensitivity 73.6%; specificity 87.2%; PV+ 68.4%; .8%). In multivariate analysis adjusted for age and comorbidities, both AIP and DPI90-120 were independently associated with ASCVD: respectively, OR 23.6 (95%CI 4.3-130.9; p < 0.001) and OR 17.8 (95%CI 3.3-97.0; p < 0.001). Conclusions: AIP and DPI90-120 were independent predictors of ASCVD. In addition, both have better diagnostic performance for ASCVD compared to the other evaluated indices, making them attractive for future trials and possible contribution to the prevention and treatment of atherosclerotic diseases. 109020 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Knowledge of Cardiopulmonary Resuscitation Manoeuvre and use of Automatic External Defibrillator by Medical Students SARA CRISTINE MARQUES DOS SANTOS1, Thais Lemos de Souza Macedo1, Joao Pedro de Resende Cortes1, Ivan Lucas Picone Borges dos Anjos1, Eduardo Tavares de Lima Trajano1, Carlos Eduardo Cardoso1, Joao Carlos de Souza Cortes Junior1, Eucir Rabello1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: With high mortality rates, the out-of-hospital cardiac arrest (OHCA) is a subject of discussion in the medical field and currently, it is emphasized the inclusion of CPR training for laymen and health professionals, in order to reduce the number of deaths and sequelae in victims. The objective of the present study was to analyze the medical students knowledge regarding the care of victims of CPR and their ability to perform this care. Methodology: This is an observational and cross-sectional study, with quantitative data collection obtained through an anonymous questionnaire, containing questions related to the recognition of a CRA and the CPR maneuver procedures by medical students during the years 2018 to 2021. Results: Of the total 468 students interviewed, 149(31.84%) answered correctly about maximum time limit from which a cardiac arrest can be considered irreversible. Regarding the use of the AED, 222(47.44%) said they knew how to use it, with 158(33.76%) reporting having learned to use it in college. Still on the AED, 265(56.62%) do not know the difference between shockable and non-shockable rhythms, but 307(65.60%) understand that this rhythm will influence in the conduct of care. Regarding the use of AED during CPR, 169(36.11%) answered correctly stating that it should be used as soon as possible. In pediatric CPR, 51(10.90%) could correctly answer regarding the depth of compressions. In the victim's pulse reassessment, 203(43.38%) did not know the correct periodicity. At the end of the questionnaire, 206(44.02%) considered themselves able to perform a CPR. Conclusion: It was possible to observe from the present study that more than half of the students do not know the ideal time to help the victim of CRA, the time of pulse reassessment during the assistance and about 90% of them, would not do the pediatric compression effectively. Regarding the AED, about 53% do not know, also not knowing the difference of the rhythm found and the need for its immediate use in a CRA. Less than half of the interviewees consider themselves capable of performing CPR. The need to implement courses in hands-on modality is emphasized, where students can realistically train the care and thus, fix it in their professional life, thus bringing benefits in post-CPR survival rates. 109023 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Automatic External Defibrillator at Cardiac Arrest: Are Medicine Students Able to Use? SARA CRISTINE MARQUES DOS SANTOS1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Joao Pedro de Resende Cortes1, Eduardo Tavares de Lima Trajano1, Carlos Eduardo Cardoso1, Eucir Rabello1, Esmeralci Ferreira2, Joao Carlos de Souza Cortes Junior1, Paula Pitta de Resende Cortes1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras; (2) Universidade do Estado do Rio de Janeiro Introduction: Cardiac arrest (CA) is defined as the sudden interruption of necessary mechanical ventricular activity and breathing. Clinically, pulse, breath, and consciousness are absent. Biologically, there is still a viable brain and other biological functions. (1) In Brazil, approximately 200 thousand individuals are victims per year of CA, 50% of them occur in extra-hospital environments such as homes, shopping centers, stadiums, airports, sports centers, among other spaces (2). In the United States of America, approximately 350,000 people die annually from CA, and, currently, the prevalence of training in cardiopulmonary resuscitation is low (3). Chest compressions associated with the use of an automatic external defibrillator (AED) are essential for survival and reducing post-CA sequelae. The present study aimed to analyze the knowledge of medical students about the use of DEA. Methods: Observational and cross-sectional, quantitative, and qualitative study between 2018 and 2019, through an anonymous survey, distributed after approval by the Research Ethics Council, addressing questions related to the knowledge of medical students about handling an AED during a CA. Results: Of 291 students interviewed, 162 (55.67%) knew how to handle an AED. Of these, 115 (39.52%) learned at college, 45 on courses (15.46%), 3 (1.03%) over the internet, 1 at work (0.34%), and 127 (43.65) did not inform or not applied. A total of 115 (39.52%) knew the difference between shockable and non-shockable rhythms. However, 190 (65.29%) reported knowing that the cardiac rhythm influences the conduct in the CA, 88 (30.24%) did not know and 13 (4.46%) did not inform. In assisting the victim of CA, 92 (31.62%) answered correctly that the AED should be used as soon as possible, 94 (32.3%) said that the use should be made later, 56 (19.24%). When asked about the locations that could identify the presence of the DEA, 92 (31.62%) mentioned shopping centers, 92 (31.62%) in universities and schools, 45 (15.46%) in gyms, 3 (1, 03%) in cinemas and 147 (50.52%) did not know. Conclusion: It was observed that slightly more than half of the students consider themselves capable of using an AED in an emergency and less than half know the difference between heart rhythms. However, they know that it will influence the conduct of the CPR. Less than a third knew the correct moment to use the AED. It shows that is necessary to implement practical workshops on CA management through universities, targ. 109024 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Efficacy of Thyroidal Hormones Supplementation in the Evaluation of Cardiac Surgeries in Pediatric Patients: A Systematic Review ISRAEL FIGUEIRA LEMOS1, Israel Figueira Lemos1, Luiz Carlos Figueiredo Filho1, Maria Eduarda Dantas da Veiga1, Mariana Lassance Maya Palheta1, Juliana de Sousa Tavares1, Ivan Cuoco Sampaio1, Rafael Augusto Silva Cabeca1, Joao Lucas Silva Sales1, Luma Maria Favacho Bordalo1, Ingrid Jade Muniz Wanderley1, Paula Larissa Baia Lima1 (1) Universidade do Estado do Para Introduction: Extracorporeal circulation, especially associated with children undergoing cardiac surgeries, is related to situations of decline in serum levels of thyroid hormones. Studies show that the rates of improvement in prognosis in surgical outcome situation in these patients can be optimized by supplementation of these hormones, due to their importance in vital functions, becoming essential in the improvement in operative outcome. Objectives: To evaluate the effectiveness of thyroid hormonal supplementation in pediatric cardiac surgeries for improvement of the operative prognosis. Methods: Systematic review using the PICO strategy and guiding question: "Does the supplementation of thyroidal hormones influence the recovery from cardiac surgery in pediatric patients?". Inclusion criteria: randomized clinical trials and articles that focus on the effect of thyroidal hormones supplementation in pediatric patients undergoing cardiac surgeries. Exclusion criteria: articles with methodological approach focused on surgical techniques rather than the supplementation of these hormones. The inclusion of articles followed the filtering protocol of the PRISMA diagram. The articles were selected from PubMed and VHL databases with the temporal delineation from 2000 to 2022. To reduce the risk of bias, Rob 2 software guidelines were used to analyze the articles. Furthermore, the descriptors used were: "thyroid hormones", "heart surgeries" and "children". Results: At first, 8 articles were found in the databases by means of the descriptors, of these, 5 fit the selective criteria. In the postoperative period, with the administration of T4, there was no improvement in hemodynamic performance or less use of mechanical ventilation in patients. Moreover, 4 studies reported in common the role of improvement in myocardial function by T3 administration, highlighting: improvement in cardiac output, reduction of systemic vascular resistance and ischemia-reperfusion lesions. In pharmacokinetic terms, doses between 0.4-0.8 mg/kg are safe and effective. Conclusion: Efficacy of thyroid hormone supplementation was evidenced in the prognostic evaluation of surgical pediatric conditions, which allowed for an improvement of the condition. A limitation of this study was the scarcity of studies, that still absent in the literature, for the comparison of the longer surgical evaluation time with the supplementation of thyroidal hormones. 109462 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Difference between Clinical, Surgical and Echocardiographic Profiles of Patients Undergoing Aortic Valve Replacement Procedure for Rapid Implant Prosthesis and Conventional Bioprosthesis PEDRO AUGUSTO MOREIRA ZAPPA1, Sergio Lima de Almeida1, Fernando Graca Aranha1, Luis Enrique Portugal1, Marli Annes1, Giani Osni Alves1, Giovanna Grunewald Vietta2, Portiuncola Gorini1, Adriana Ferraz Mrtins1, Jose Fernando Arruda1, Roberta Luiza Salum1 (1) Hospital SOS Cardio; (2) Universidade do Sul de Santa Catarina Background: The high prevalence of patients with aortic stenosis has led to the development of new surgical treatment options, such as rapid implant valves. These can reduce transoperative times, which are crucial for reducing complications for patients benefiting from this type of prosthesis. Objective: To evaluate the difference between the clinical, surgical and echocardiographic profile of patients undergoing aortic valve replacement procedure using rapid implant prosthesis and conventional bioprosthesis. Method: Case-control study, carried out at Hospital SOS-Cardio in Florianopolis; population of 60 cases and 119 controls, the controls were selected at random. The variables studied were demographic, clinical, surgical and echocardiographic factors, in order to identify differences between the times of aortic clamping and extracorporeal circulation. Results: 73.3% of patients in the case group were at high risk, compared to 39.5% of controls (p < 0.001). Mortality was similar between groups (p > 0.999). The CPB time was on average shorter for the case group (72.35 +- 18.459 minutes), as well as the Clamp time (62.87 +- 16.802) (p < 0.001). The mean transvalvular gradient differed between groups: 7.95 +- 2.74 mmHg for cases, and 13.19 +- 13.142 mmHg for controls (p < 0.001). Conclusion: The study demonstrated a reduction in cardiopulmonary bypass times and aortic clamping in the case group, as well as, this same group showed better hemodynamic performance in the prosthesis implanted in it. There was no difference in mortality between the groups, which demonstrated a better result when using the rapid implant prosthesis, as it presented significantly increased risks. 109032 Modality: E-Poster Scientific Initiation - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Humanized Medicine. What is the Impact on the Quality of the Patient's Hospitalization? SARA CRISTINE MARQUES DOS SANTOS1, Ivan Lucas Picone Borges dos Anjos1, Livia Liberata Barbosa Bandeira1, Thais Lemos de Souza Macedo1, Eucir Rabello1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Promoting the approach of medical students to patients aims to encourage the implementation of humanization in the doctor-patient relationship1. In a study carried out in 2008, a total of 82.5% of respondents who were under hospitalization, considered themselves stressed3. Because of the stress observed during hospitalization and the benefit that humanization of care can bring to patients, the objective was to bring first-time medical students closer to patients admitted to a teaching hospital with a humanized focus and to evaluate through questionnaires anonymously. Methodology: Prospective, observational, and cross-sectional study, with the opinion of the Research Ethics Council (CEP) No. 1,963,944 and carried out from 2017-2019 under the guidance of teachers to first-time medical students in accompanying hospitalized patients with vision humanized as a person. An anonymous questionnaire of quick responses to patients was administered on the participation of students during hospitalization. Results: A total of 1732 hospitalized patients were interviewed and 1156 (66.7%) considered the participation of students with a humanized focus as excellent; 492 (28.4%) as good; 69 (4%) as regular and only 09 (0.5%) as poor, with 06 (0.3%) not responding. They considered that the student's participation during hospitalization was positive, bringing more comfort and tranquility to patients, according to the reports of the questionnaires, during hospitalization, seeking to supply problems reported by patients in various areas reported. Of the total group, 835 (48.2%) of them reported that their hospitalization was responsible for the occurrence of disorders in their routine, 351 (42%) being concerned about the disease, 235 (28.1%) reporting communication problems with family members, 232 (27.8%) with work, financial 151 (8.7%), 24 (1.4%) problems with personal hygiene and 48 (2.7%) did not report. Conclusion: Humanization in hospitalized patients stands out as an important tool in the treatment because of the reduction of stress generated by the disease and hospitalization. The present study demonstrated that 95.15% of the patients perceived the student's participation as positive from the humanized point of view. Humanized treatment should be encouraged by the doctor's initial training, contributing to stress reduction, optimizing treatment. 109043 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION The Increment in Aerobic Capacity is Correlated with Lower Wall Motion Score Index After Exercise in Patients with Chronic Coronary Syndrome CLAUDIA BISPO MARTINS SANTOS1, Gabriela de Oliveira Salazar1, Jose Icaro Nunes Cruz1, Lucas Villar Shan de Carvalho Cardoso1, Ana Luisa Lisboa Prado1, Giulia Vieira Santos1, Leticia Luiza Gomes Marques1, Arthur Leite Lessa1, Edvaldo Victor Gois Oliveira1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Federal University of Sergipe Introduction: Physical exercise leads to cardiovascular and autonomic adaptations essential for most favorable prognosis of chronic coronary disease (CCD), increasing aerobic capacity expressed by maximal oxygen consumption (VO2MAX). Objective: To analyze the behavior of cardiorespiratory capacity in patients with CCD undergoing Exercise Stress Echocardiography (ESE). Methods: Cross-sectional study between January/2000 and January/2022 of patients with CCD who underwent ESE at a cardiology referral service in Sergipe (Brazil). A total of 2000 patients (61.04 +- 10.17 years) were categorized as sedentary or active according to the definitions of the World Health Organization. Student's t test or Mann-Whitney test and chi-square test was used. The correlation of VO2MAX with clinical variables was evaluated using Pearson's or Spearman's tests. A significance level of 5% was adopted. Analyzes were performed using SPSS Statistics software. Results: A total of 1033 (51.66%) sedentary and 967 (48.34%) active individuals were evaluated. The active patients reached higher VO2MAX (35.41 vs. 30.48 mg/kg.min; p < 0.001) and, the sedentary, higher diastolic pressures after exercise (85.05 vs. 83.99 mmHg; p = 0.003). Sedentary lifestyle was associated with the female sex (45.5% vs. 34.7%; p < 0.001). VO2MAX was negatively correlated with resting systolic blood pressure, wall motion score index after exercise and age - being those relationships stronger in the active group; resting diastolic blood pressure was positively correlated with VO2MAX only in sedentary individuals - Table 1. Conclusions: Practicing physical exercise permitted the increase of aerobic capacity, reducing systolic pressure levels at rest and correlating with lower wall motion score index after exercise. 109048 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Myocardial Ischemia and Smoking on Post-Acute Myocardial Infarction Patients Undergoing Exercise Stress Echocardiography CLAUDIA BISPO MARTINS-SANTOS1, Jose Icaro Nunes Cruz1, Gabriela de Oliveira Salazar1, Juliana Maria Chianca Lira1, Lucas Villar Shan de Carvalho Cardoso1, Mayara Evelyn Gomes Lopes1, Marilia Marques Aquino1, Octavio Morais Veloso1, Giulia Vieira Santos1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Federal University of Sergipe Introduction: Despite the clear association between smoking and atherosclerotic diseases, the discussion about the smoker's paradox persists, given the low reactivity of platelets induced by smoking. Objective: To evaluate the occurrence of smoking-related myocardial ischemia (MI) in patients with previous Acute Myocardial Infarction (AMI) submitted to Exercise Stress Echocardiography (ESE). Methods: Cross-sectional study between January/2000 and January/2022 with individuals presenting a positive history for AMI who underwent ESE at a cardiology referral service in Sergipe (Brazil). A total of 737 patients (61.01 +- 10.78 years) were categorized according to tobacco exposure: smokers, former smokers and non-smokers. Analysis of variance (ANOVA) was used for multiple comparisons with post-hoc Bonferroni and the chi-square test were applied. A significance level of 5% was adopted. Binary logistic regression was performed to identify whether smoking was independently associated with MI. To enter the model, the significance level was p < 0.10 and, to remain, p < 0.05. Analyzes were performed using SPSS Statistics software. Results: Fifty-four (7.33%) smokers, 581 (78.83%) ex-smokers and 102 (13.84%) non-smokers were evaluated, which did not presented differences in the distribution of sex, systemic arterial hypertension, family history and systolic and diastolic blood pressures at rest (p > 0.05). The age was higher on the non-smoker group when compared to smokers (63 vs. 58 years; p = 0.022). Smokers were more likely to be diabetics (p = 0.0037), and ex-smokers, non-diabetics (p = 0.0010). Former smokers were generally non-dyslipidemic (p = 0.0051), while non-smokers were dyslipidemic (p < 0.0001). The chance of having MI was higher among smokers (OR = 2.44; 95%CI 1.14-5.22; p = 0.022) and former smokers (OR = 2.24, 95%CI 1.42-3.53, p = 0.001). Conclusions: When evaluating post-AMI patients, being a former smoker was independently associated with MI. The predictive model also showed that the chance of having MI was even greater among those who continued to smoke. 109050 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Associated Factors on Myocardial Ischemia Without Obstructed Coronary Arteries (INOCA) CLAUDIA BISPO MARTINS-SANTOS1, Jose Icaro Nunes Cruz1, Gabriela de Oliveira Salazar1, Ullany Maria Lima Amorim Coelho de Albuquerque1, Myllena Maria Santos Santana1, Lucas Villar Shan de Carvalho Cardoso1, Marilia Marques Aquino1, Nathalia Luiza Silva Sobral1, Lara Teles Alencar Duarte1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Federal University of Sergipe Introduction: When myocardial ischemia (MI) is documented and there is no obstruction of coronary arteries, the diagnosis of ischemia with no obstructive coronary artery disease (INOCA) is established, which has an adverse prognosis. Objective: To analyze the factors associated with the absence of obstructive coronary artery disease (CAD) in patients with MI. Methods: Cross-sectional study between January/2000 and January/2022 with individuals presenting MI on Exercise Stress Echocardiography carried out at a cardiology referral service in Sergipe (Brazil). A total of 1631 patients (59.80 +- 10.56 years) were analyzed, divided into patients with INOCA - defined by coronary angiography - and with obstructive CAD. Mann-Whitney and chi-square tests were applied. A significance level of 5% was adopted. Analyzes were performed using SPSS Statistics software. Results: 500 (30.66%) individuals had INOCA and 1131 (69.34%) had CAD. Patients with INOCA were more likely to be female (56.6% vs. 35.6%; p < 0.0001). The INOCA group showed a lower tendency to have dyslipidemia (57.0% vs. 70.4%; p < 0.0001) and a positive family history of cardiovascular diseases (54.6% vs. 64.2%; p < 0.0001). There was no association between absence of CAD on MI and the factors: hypertension, diabetes mellitus and obesity (p > 0.05). Patients with INOCA tended to be younger (58 vs. 60 years; p < 0.0001) and the analyses of wall motion score index at rest and after exercise dit not presented significant differences (p > 0.05) between the groups. Systolic blood pressure levels at rest and after exercise did not differ between INOCA and CAD (p > 0.05). Conclusions: Female sex, absence of dyslipidemia and negative family history for cardiovascular events were factors associated with INOCA. There was no difference in the involvement of left ventricular motility, which suggests that ischemia in patients with CAD and INOCA has a similar degree. 109052 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Elevated Levels of Native T1 Myocardial Mapping in Patients Without Late Enhancement CLAUDIA BISPO MARTINS-SANTOS1, Gabriela de Oliveira Salazar1, Jose Icaro Nunes Cruz1, Nathalia Luiza Silva Sobral1, Juliana Maria Chianca Lira1, Lara Teles Alencar Duarte1, Raisan Almeida Santos2, Giulia Vieira Santos1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1, Luiz Flavio Galvao Goncalves2 (1) Federal University of Sergipe; (2) Hospital Sao Lucas Introduction: Cardiovascular magnetic resonance (CMR), through the myocardial T1 time mapping technique, provides the tissue characterization of myocardial fibrosis, both localized and diffuse, in a quantitative manner, in order to overcome some limitations of the evaluation of late enhancement. Objective: To analyze CMR parameters in relation to the increase in native T1 map levels in patients without delayed enhancement, in order to demonstrate its role as a marker of advanced heart disease. Methods: Cross-sectional study between January and December 2021 with individuals undergoing CMR who did not present late enhancement at a cardiology referral service in Sergipe (Brazil). A total of 131 patients (54.54 +- 16.96 years) were analyzed, divided into two groups according to the increase (>=1030 ms) or not (<1030 ms) in the levels of native T1 acquired by the modified look locker method (MOLLI) in a magnetic field of 1.5 Tesla. Student's t, Mann-Whitney and chi-square tests were applied. A significance level of 5% was adopted. Analyzes were performed using SPSS Statistics software. Results: 47 (35.88%) individuals had increased levels of native T1 and 84 (64.12%) presented levels below 1030 ms. The group with increased T1 had more females than the group without increased T1 (72.3% vs. 32.1%; p < 0.0001). Patients with increased native T1 levels had lower left ventricular ejection fraction values when compared to those with normal T1 levels (56.32% vs. 62.35%; p = 0.014). The group with high native T1 had even lower values of left ventricular mass (95.34 g vs. 105.41 g; p = 0.027), right ventricular end-diastolic volume (108.89 ml vs. 129.52 ml; p = 0.007) and right ventricular measurements at short axis orientation (3.66 cm vs. 3.99 cm; p = 0.001). Conclusions: Elevated levels of native T1 mapping were associated with female sex, as well with lower left ventricular mass and ejection fraction values in those patients without late enhancement. Therefore, the role of CMR in the assessment of ventricular function is reiterated and its application in patients without late enhancement is demonstrated. 109069 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Epidemiological Study of Morbidity and Mortality from Acute Myocardial Infarction Reported in Brazil between 1999 and 2019 FILIPE ALVES RAMOS 1, Augusto De Marco Martins2 (1) Catholic University of Brasilia; (2) Biocardio Institute Introduction: Acute myocardial infarction is one of the main causes of death in Brazil. According to the Ministry of Health, risk factors such as (1) smoking, (2) dyslipidemia, (3) hypertension, (4) obesity, (5) diabetes, and (6) stress have contributed to an increase in the number of deaths associated with infarction, and thus, generating social and economic impacts on the Brazilian society. Objective: To investigate the number of deaths associated with Acute Myocardial Infarction in Brazil between 1999 and 2019. Methods: This is a cross-sectional epidemiological study carried out between 1999 and 2019 on the number of deaths from acute myocardial infarction reported in Brazil. The analysis of information had been extracted from the Department of Informatics of the Brazilian Unified National Health System (DATASUS). Results: In the analyzed period, 1,610,781 deaths from acute myocardial infarction were reported in Brazil. There was a 28.42% increase in the mortality rate in 2019 when compared with the rate reported in 1999. The number of deaths in Brazil in 2019 (95,557 deaths) was 65.00% higher than in 1999 (57,913 deaths). The male sex was the most afflicted and corresponded to 59.03% of the deaths reported in that period. Regarding the deaths by race, it was observed that white people (57.03%) and pardo people (29.48%) were the most affected. When grouped by age, it was observed a higher frequency of mortality rate between 70 to 79 years old: 411,161 (25.53%); followed by 80-year-olds: 380,371 (23.61%); 60 to 69 years: 378,933 (23.52%); 50 to 59 years: 263,790 (16.38%); 40 to 49 years: 126,090 (7.83%); 30 to 39 years: 37,176 (2.31%) and under 30 years old: 11,244 (0.70%). In 2019, the mortality rate per 100,000 people in Brazil was 45.36. Regarding the numbers by region, it was noted that the southeast region was responsible for 48.45% of deaths reported in Brazil in the analyzed period. Conclusions: In the light of the results obtained, it was verified that the mortality rate and the number of deaths due to acute myocardial infarction increased over the years. In this study, it was observed a higher frequency of deaths from acute myocardial infarction among white men over the age of 50. Therefore, it is essential to promote health campaigns against stress, sedentary lifestyle, and poor diet, which are aimed at the prevention of coronary artery disease. 109074 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH What Factors Influence Brazilian Medical Students to Pursue a Career in Cardiology? MARYANA HELENA DE SOUZA MENDONCA RIBEIRO1, Jeanne du Fay de Lavalla2, Luciene Ferreira Oliveira Mota3, Annabelle Santos Volgman4 (1) Medicine College of Itajuba, Itajuba, MG, Brazil; (2) Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.; (3) Department of Cardiology, Medicine College of Itajuba, Itajuba, MG, Brazil; (4) Division of Cardiology, Rush University Medical Center, Chicago, IL USA Introduction: While a diverse workforce improves the care of patients, encourages different views, and reduces bias in the working environment, female cardiologists continue to be <30% of the workforce in the United States and Brazil. Therefore, including women's recruitment as a priority for the cardiology community through understanding and discovering what inspires women to follow a cardiology career is essential. We conducted a survey of students from a Brazilian medical school to ascertain their motivations to consider cardiology and sought to find sex differences among the students. Objective: Identify factors which affect medical students' interest in cardiology and assess any sex differences. Methods: Medical students answered a digital survey based on the science interest survey, validated by the Rasch scale and modified to address cardiology interest questions. The survey consisted of 20 questions, answered in the Likert scale and divided into five categories: class, family, friends, informal (learning outside the classroom), and professors. Altogether, 100 medical students (28 men/72 women) from the first to sixth year answered this survey. p < 0.05 was considered significant. Results: In both sexes the influence of professors had higher median ratings compared to the classes, family, friends, and informal. Friends had the least influence on students' interest in cardiology. There were no significant sex differences. Conclusion: In this cohort of Brazilian medical students, professors had the most influence on encouraging medical students into pursuing cardiology. In the same way, practical classes in cardiology wards and visits to specialized centers appeared to be a good alternative to inspire men and women on becoming cardiologists. 109075 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Safety of COVID-19 Vaccines Among Individuals with Cardiopathies Assisted in an Outpatient Facility in Brazil ANA LUISA SOARES CHIARETTI1, Bianca de Almeida Nunes2, Livia Brito Oliveira2, Glicia Gleide Goncalves Gama2, Fabio Figueiredo Costa2, Adriana Lopes Latado2 (1) Faculdade de Medicina da Bahia da Universidade Federal da Bahia - FMB-UFBA; (2) Hospital Universitario Professor Edgar Santos da Universidade Federal da Bahia/Empresa Brasileira de Servicos Hospitalares - HUPES-UFBA/EBSERH Introduction: The rapid development of effective and safe vaccines was set as a priority due to the COVID-19 pandemic. This acceleration generated an infodemic, raising questions about the safety of the vaccines between the population, including cardiac patients. Objectives: Evaluate the safety of COVID-19 vaccination in patients with cardiopathies. Methodology: Unicentric prospective observational cohort that evaluated vaccination cover, frequency and severity of adverse events (AE) associated with the COVID-19 vaccines between patients with cardiopathies followed up in a cardiology referral service, in Salvador, Bahia, Brazil, between 2021 and 2022. AE were defined as any unwanted medical occurrence after the vaccination, which were categorized as severe (SE) or non-severe (NSE) events. Descriptive analysis of the data were performed and the inferential analyses were exploratory. Significance level adopted was 5%. Results: 259 patients were included, 65,4% were women, 83,3% were black or brown. The average age was 62.4 (+15.8) years). Among morbidities, 81,4% had arterial hypertension, 44,6% had diabetes mellitus, 23% had chronic kidney disease, 78,7% had dyslipidemia, 16,3% had atrial fibrillation, 11,2% had previous myocardial infarction and 36,6% were diagnosed with heart failure. With regard to vaccination, 84,3% (204) had received at least two doses of vaccine, of which 38,0% received the CoronaVac, 30,2% (78) received the AstraZeneca, and 15,1% received Pfizer. 1,9% received a single dose of Janssen and 14,7% (38) did not know about vaccine type. By the end of the study, 35,6% had received a third dose of vaccine, 97,5% (81) were given Pfizer and 2,5% were given CoronaVac. Of total vaccinated, 30% reported NSE (local soreness, fever, myalgia or headache, during less than 3 days) and no SE (life-threatening events, requirement of hospitalization or causes of permanent sequelae) were reported. Patients who reported AE were younger (56,5 + 15,1 vs 65,5 + 14,9 years; p < 0,01), mostly women (36,8% vs 18,3% p = 0,01) and without hypertension (40,6% vs 34%, p = 0,04). The AE were more frequently reported after vaccination with adenovirus carrier or RNA vaccines (AstraZeneca, Janssen and Pfizer) than with Coronavac (p < 0,01). Conclusion: The COVID-19 vaccines available in Brazil are safe for application in patients with cardiopathies. AE were frequent but without gravity, being more frequent in women and after vaccination with adenovirus carrier or RNA immunizers. 109122 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Chronic Rheumatic Cardiopathy in the Northern Region of Brazil: A Ten-Year Analysis in the Single Health System LEO CHRISTYAN ALVES DE LIMA1, Hildeman Dias da Costa2, Laura Jane Franca Lacerda1, Matheus Akira Suzuki de Oliveira2, Leticia Luana Alves Ferreira1, Emanuelle Toneto Souza Silva1, Andressa Flores da Costa1, Carla Cibelly Mesquita Almeida1, Joao Paulo Lucena1 (1) Centro Universitario Sao Lucas (UniSL); (2) Universidade Federal de Rondonia (UNIR) Introduction: Chronic rheumatic heart disease (CRHD) is a non-suppurative complication of pharyngotonsillitis caused by group A beta-hemolytic streptococcus and results from a delayed immune response in genetically predisposed populations. It is a leading cause of cardiovascular disease in developing countries, accounting for approximately 15 percent of all heart failure patients in endemic countries. Objectives: To describe the epidemiological profile of hospitalizations for Chronic Rheumatic Heart Disease in adults between the years 2009 and 2019. Methodology: Epidemiological, descriptive, retrospective study. Data were obtained from the IT department of the Unified Health System - DATASUS, from January 2009 to December 2019, with individuals aged 20 to 79 years, evaluating hospitalization rates, mortality and pattern of carriers: range age, race and sex. Results: In the analyzed period, 3830 hospitalizations were observed, 2052 were female and 1778 were male. Regarding race, there were 2089 occurrences in pardos, 272 in whites, 76 in blacks, 20 in yellows, 7 in indigenous people. The age group with the highest number of cases was between 40 and 49 years, with 777 individuals. The average total hospital stay was 14 days, representing a total expense of R$31,020,178.05, with 2017 being the year with the highest number of hospitalizations (534) and 2010 the lowest number (295). The total mortality rate was 9.63, with the state of Amapa having the highest rate (18.37), followed by Rondonia (12.27), with a peak in 2014 (17.49). The total number of deaths corresponded to 369 deaths, with the state of Para holding the highest number (143), followed by Amazonas (87). Conclusion: CRHD is still a major public health problem, especially in developing countries, resulting in huge health expenditures. The present study demonstrated a large number of cases of the disease in the northern region of Brazil. Between the years 2009 to 2019, the epidemiological profile was characterized by females, brown, aged between 40 and 49 years. The state with the highest number of cases was Para and the highest mortality rate found was in Amapa. The description of these sociodemographic and epidemiological characteristics guide the planning of health actions in order to improve the population's quality of life. 109124 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hypertension and Heart Rate: Insights from a National Study with Brazilian Adolescents DOMINGOS ALVES DE SANTANA NETO1, Anna Mayse Feitosa da Silva1, Mariana Evaristo Leite2, Sarah Mariani Rocha Oliveira1, Ana Beatriz Vaz de Araujo1, Katia Vergetti Bloch1 (1) Universidade Federal do Rio de Janeiro (UFRJ); (2) Universidade Federal de Sao Joao del-Rei (UFSJ) Introduction: Hypertension (HTN) is one of the main risk factors for cardiovascular diseases. Hypertensive adolescents are at higher risk of becoming hypertensive adults. Heart rate (HR) is a simple measure associated with sympathetic activity and can be influenced by numerous environmental factors. Elevated resting HR in adolescents can be a predictor of HTN in adults. Objective: To explore the association of Hypertension with Heart rate in Brazilian adolescents. We also aimed to investigate the influence (confounding or effect modification) of sex, age, physical activity, and obesity in this association. Methods: The Study of Cardiovascular Risks in Adolescents (ERICA) was a national, school-based, cross-sectional study. The sample has a complex design, being composed of adolescents aged between 12 and 17 years old from public and private schools located in Brazilian municipalities with more than 100,000 inhabitants. Data were collected using a self-administered questionnaire on an electronic device. Blood pressure and heart rate at rest were measured with an oscillometric device. Weight and height were measured to calculate the body mass index (weight/height2), classified according to WHO reference curves by sex and age. Physical activity was evaluated using a list of 24 modalities, including information on frequency (days) and time (hours and minutes) of practice during the last week. Adolescents who accumulated more than 300 min/week of physical activity were classified as active. Raw and adjusted linear regression models were performed in Stata 15.0. Results: Age and obesity were confounding variables, while sex and physical activity were effect modifiers for the association between Hypertension and Heart rate (p < 0.001 for interaction). Girls and hypertensive adolescents had the highest Heart rate levels (88.5 bpm; 95%CI 87.0 to 90.0), while boys and non-hypertensive adolescents had the lowest (78.1 bpm; 95%CI 77.6 to 78.5) adjusted for age and obesity. The Heart rate of hypertensive and inactive adolescents was 87.6 bpm (95%CI 86.0 to 89.1), and non-hypertensive and active adolescents was 79.1 bpm (95%CI 78.6 to 79.5). Conclusion: The observed association of Hypertension with Heart rate was independent of age and obesity. The effects of sex of physical activity on this association should be considered in longitudinal studies to estimate the prediction. 109217 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Acetylsalicylic Acid for Preventing Preeclampsia and Complications: A Systematic Review RAYANNE ALESSANDRA DA SILVA BARRETO1, Anderson Brasileiro de Araujo1, Ana livia Gadelha Xavier da Nobrega1, Beatriz Gadelha e Xavier1, Bianca Vasconcelos Braga Cavalcante1, Leticia Lacerda Burity1, Vinicius Vieira Leandro da Silva1 (1) Faculdade de medicina Nova Esperanca-FAMENE Introduction: Preeclampsia is defined as hypertension (systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg), arising after 20 weeks of gestational age with proteinuria (300 mg) or other signs of end-organ damage and is an important cause of maternal and perinatal morbimortality, particularly when of early onset associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that doses greater than 80 mg/day of acetylsalicylic acid, might delay or prevent development of preeclampsia. Prophylaxis is recommended in women at high risk of this disease that includes history of preeclampsia, chronic hypertension, family history of preeclampsia, renal disease, a body mass index greater than 30, multifetal gestation, and sociodemographic characteristics. Should be initiated between 12 weeks and 28 weeks of gestation, optimally before 16 weeks, and continued daily until delivery. Objective: To assess the effectiveness and safety of doses greater than 80 mg/day of acetylsalicylic acid (ASA), in early pregnancy with increased risk of preeclampsia with the objective of delaying or preventing this disease. Methods: Keywords were combined for electronic databases search. Relevant citations were extracted from PubMed, Elsevier and web science from 2007 to 2021. This systematic review includes only randomized, controlled trials. The population in the studies involved pregnant women at risk of preeclampsia treated with aspirin low-dose initiated at or before 16 weeks of gestation. Results: 17 trials (n = 15.908) to assess maternal and perinatal health outcomes and 15 trials (n = 15.767; 10 good-quality) to assess prevention of preeclampsia. All trials were placebo-controlled. ASA treatment beginning in early gestation was associated with a greater reduction in the incidence of preeclampsia than treatment beginning in late gestation. Conclusions: Daily low-dose acetylsalicylic acid use in pregnancy is considered safe. Treatment with this drug initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. 109129 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Overview of Acute Myocardial Infarction (AMI) Cases in the Regions of Brazil: A Comparative Analysis between a Period Before and During the COVID-19 Pandemic MARINA DE ANDRADE BATISTA1, Ana Verena Silva Santos1, Daiane Lima dos Santos2 (1) Cetro universitario UniFTC; (2) Universidade Estadual da Bahia Introduction: According to the Brazilian Society of Cardiology (2015), there are about 350 thousand new cases of Acute Myocardial Infarction (AMI) per year and 40 to 65% of them evolve to death in the first hours. Among cardiovascular diseases, AMI has one of the highest rates of morbidity and mortality. In the period of the COVID-19 pandemic, given the restrictions to seek health services, the possibility of underreporting of AMI cases in the country is raised. In addition, from 2019 to 2020, there was a decline of 89.97% in patients who sought the cardiology outpatient clinic. Therefore, given this public health problem, there is an urgent need to analyze the registration of these cases in regional units in Brazil. Objective: To analyze the number of confirmed cases of acute myocardial infarction, before and during the Covid-19 pandemic, among the Regional Units of the Brazilian territory, comparing the periods from 2017 to 2019 and 2019 to 2022. Method: This is a retrospective epidemiological study of an analytical nature, carried out using data published on the Ministry of Health portal from 2017 to 2022. For this study, confirmed cases of AMI were analyzed by Regional Unit from 2017 to 2022. Appraisal by the Research Ethics Committee is unnecessary because this research used public data, without identification of the participants. Results: In the analyzed period, 738,196 cases of AMI were confirmed in Brazil, with 362,649 in the pre-pandemic period (1) 2017 to 02/2019 and 370,547 in the pandemic period (2) from 03/2019 to January 2022. Studying the regional units in period 1, the following stand out: Southeast with 49.3% (n = 178,942), Northeast with 19.7% (n = 71,509) and South with 19.3% (n = 70,021) of cases. In period 2, regional highlights were in charge of the same regional units, respectively, with 48.8% (n = 180,945) of cases, 19.8% (n = 73,724) and 18.8% (n = 69,868). Therefore, during the pandemic, there was an increase of 2.1% (n = 7,898) compared to the pre-pandemic period. Conclusion: While access to health services has declined during the pandemic, AMI records have increased. However, given the possible underreporting, it is inferred that the increase was even more significant. Since AMI has high morbidity and mortality, many individuals were left without proper assistance during this period, increasing their susceptibility to AMI and its complications. 109131 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Impact of Atrial Fibrillation on Left Atrial Function Following Percutaneous Mitral Valvuloplasty ANA CLARA DE PAULA CALDAS1, Ana Clara de Paula Caldas1, Juliana Rodrigues Soares2, Vinicius Tostes Carvalho2, Lucas Lodi-Junqueira2, Guilherme Rafael Sant'Anna Athayde2, Paulo Henrique Melo1, Fernando Coutinho1, Lucas Posoli1, Pedro Emanuel Carvalho1, William Antonio M. Esteves1, Maria Carmo Pereira Nunes2 (1) Universidade Federal de Minas Gerais (UFMG); (2) Hospital das Clinicas da Universidade Federal de Minas Gerais (HC - UFMG) Background: Rheumatic mitral stenosis (MS) results in elevated left atrial (LA) pressures and subsequent atrial remodeling, atrial fibrillation (AF), and thrombus formation. Progressive LA enlargement can occur, despite the relief of valvular obstruction with valve intervention. This study evaluates LA function by three-dimensional echocardiography (3DE) in rheumatic MS patients undergoing percutaneous mitral valvuloplasty (PMV) to assess the impact of AF on LA function. Methods: A total of 160 MS patients referred to PMV were prospectively enrolled. LA volumes and function were measured by 3DE pre, immediately after PMV, and at 1 year follow-up. Results: Mean age was 44 +- 12 years, and 134 (84%) patients were women. Pre PMV, 44 (28%) were in AF, and 66 (41%) were in NYHA functional class III or IV. LA maximum volume decreased from 55.5 +- 23.1 ml/m2 to 53.5 +- 29.7 ml/m2 48 hours after the procedure (p = 0.147), and to 50.5 +- 24.6 ml/m2 at 1 year follow-up (p = 0.011). LA emptying fraction increased from 20.4 +- 10.1 ml/m2, to 28.7 +- 11.4 ml/m2 after 48 hours of procedure (p < 0.001), and to 32.6 +- 13.3 ml/m2 at 1 year follow-up (p = 0.003). In AF patients, LA emptying fraction was 13.8 +- 7.5% at baseline, 21 +- 9.3% 48 hours after the procedure (p = 0.039) and 20.8 +- 8.7% at follow-up (p = 0.946) . Age, initial presence of AF, and postprocedural mean gradient were identified as the most significant predictors of late LA function. Conclusions: LA presents reverse remodeling after PMV. This remodeling is higher immediately after the procedure, but continues to occur in the following months. In patients with MS and AF, volumes remained unchanged after PMV, either at 48 hours and at follow up, and only the emptying fraction improves at 48 hours, without further improvement at follow up. 109143 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Comparative Analysis of the Epidemiological Panorama of Hospitalizations and Deaths in Patients with Pulmonary Embolism in the Periods Pre, During and Post-Covid 19 Pandemic ERICK BRODER BICHARA1, Victor Arthur Soares Costa Araujo1, Diego Moreira Arruda1 (1) Escola Bahiana de Medicina e Saude Publica Background: Pulmonary embolism (PE) is one of the most frequent underdiagnosed acute cardiovascular diseases. In the COVID-19 first wave, especially, there were many disorders with similar symptoms. The pandemic has created an atmosphere of uncertainty among healthcare professionals and this fear leaded to a pulmonary embolism diagnosis even more underdiagnosed within the focus on COVID cases. Increased D-dimer works as a predictor for the presence of COVID. This indicator is still an essential factor for diagnosis PE, and it's increase in patients with COVID can result in prothrombotic state. Methods: Quantitative, descriptive study, carried out using secondary data from the Hospital Information System of DataSUS, about the monthly frequencies of hospitalizations and deaths related to pulmonary embolism. Objective: Describe the epidemiological profile of hospitalizations and deaths resulting of pulmonary embolism in periods pre, during and post-COVID-19 pandemics in Brazil. Results: In pre-pandemic period (Apr/19-Jan/20), there were 7915 hospitalizations in the country, 1948 in capitals. 2979 hospitalizations occurred in men and 4936 in women. Age group 60-69 years (1496) led. As for deaths, there were 1387 in country, 344 in capitals. 560 deaths in men and 827 in women. The age group 80 years and over (358) led. In 1st wave period (Feb/20-Nov/20), there were 7173 hospitalizations in country, 1777 in capitals. An increasing pattern was observed between Dec/19-Feb/20 (28, 141 and 222) - pandemic beginning - and a decreasing between Oct/20-Nov/20 (187 and 79) - end of the first wave. 2803 hospitalizations occurred in men and 4370 in women. Age group 60-69 years (1406) led. As for deaths, there were 1289 in country, 351 in capitals. 527 deaths in men and 762 in women. Age 80 and over (333) led. During vaccine period (Jan/21-Oct 2021), there were 8087 hospitalizations in country, 1936 in capitals. This period had the highest number among the three periods (1042 in Jul/21). There was an increasing pattern from Aug/20-Apr/21 (4, 6, 23, 47, 109, 178, 182, 185, 232) and a decreasing from Jun/2021-Oct/21 (256, 253, 196, 151, 97). 3440 hospitalizations occurred in men and 4647 in women. Age group from 60-69 years (1565) led the cases. As for deaths, there were 1585 in country and 387 in capitals. 692 deaths in men and 893 in women. Age 80 and over (402) led. Conclusion: Both cases and deaths decreased during 1st wave period and increased during vaccine period. 109708 Modality: E-Poster Scientific Initiation - Non-case Report Category: PSYCHOLOGY The Relationship and Benefits of Psychotherapy in Patients After Cardiac Surgery VINICIUS VIEIRA LEANDRO DA SILVA1, Leticia Lacerda Burity1, Beatriz Gadelha e Xavier1, Bianca Vasconcelos Braga Cavalcante1, Ana Livia Gadelha Xavier da Nobrega Pereira1, Rayanne Alessandra da Silva Barreto1, Giovanna Alves de Souza2, Eduardo Franco Correia Cruz Filho3, Salmo Vasser Paranhos de Oliveira4, Beatriz Calsolari Ranha5, Idemar Luis Cover Filho6, Luis Fernando Brito Ferreira7 (1) Faculdade de Medicina Nova Esperanca (FAMENE); (2) Universidade Cidade de Sao Paulo (UNICID); (3) Centro Universitario de Joao Pessoa (UNIPE); (4) Universidade: Instituto de Ensino Metropolitano de Ensino Superior (IMES - Univaco); (5) Universidade do Estado do Rio de Janeiro (UERJ); (6) Faculdade Ciencias Medicas (FCM); (7) Centro Universitario Facisa (FACISA) Introduction: Cardiovascular diseases (CVDs) are the leading cause of death in the world, bringing concern to the main global health agencies. Among the risk factors for CVDs, emotional aspects are increasingly being associated with increased cardiovascular risk. In the clinical practice of cardiac surgical patients, it is observed that psychological factors such as depressed mood, anxiety and fear of dying influence the patient's recovery. Objective: This abstract aims to show the benefits of psychotherapy in patients after cardiac surgery, and its relationship with cardiovascular disease. Methods: This is an integrative review based on relevant publications on databases of the Latin American and Caribbean Literature on Health Sciences Information (LILACS), Scientific Electronic Library Online (SciELO), Virtual Health Library (BVS) and PubMed, in English and Portuguese from 2007 to 2020. Results: It is known that the frequency of psychiatric disorders in hospitalized patients after cardiac surgery is between 20 and 60%, where anxious and depressive disorders due to fear of loss of autonomy or death stand out. Psychotherapy has brought several benefits to hospitalized patients, where there has been a reduction in the symptoms of psychological disorders, greater adherence to medication and diet, and an improvement in the acceptance of the procedures performed, leading to a reduction in the number of hospitalization days, helping in a better patient recovery. Conclusions: Therefore, we can conclude that the support of psychotherapy in patients who have undergone cardiovascular surgery has brought relevant results, causing a faster and more comfortable recovery for hospitalized patients. 109182 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Chronotropic Index as a Predictor of Mortality in Patients with Coexisting Heart Failure and Atrial Fibrillation GUILHERME OLIVEIRA MAGALHAES COSTA1, Bruno Oneto Y Viana Pintos2, Mauricio Pimentel2, Anderson Donelli da Silveira2 (1) Universidade Federal do Rio Grande do Sul (UFRGS); (2) Hospital de Clinicas de Porto Alegre (HCPA) Introduction: Atrial fibrillation (AF) is associated with a worse prognosis in patients with heart failure (HF). A blunted chronotropic response seems to be related to worse prognosis and functional capacity in those patients, independently of beta-blocker use. Objectives: To evaluate heart rate response during cardiopulmonary exercise testing (CPET) in patients with both HF and AF and its association with cardiovascular events. Methods: Retrospective cohort study including patients with HF and AF assessed by CPET, followed-up in an outpatient clinic at a public university hospital. The primary endpoint was death or need for heart transplant. T-Test for independent samples or Mann-Whitney U test were used when appropriate. The best cut-off point for the chronotropic index was obtained by a ROC curve analysis. Univariate and multivariate survival analysis was performed using Cox regression and Kaplan-Meier curve. Results: A total of 1083 patients with HF comprised the entire cohort, 208 of those with coexisting AF. Mean age was 58 (+-11) years and average follow-up time was 42 (+-20) months. 31% were female, 19% ischemic, 15% had HFpEF, 85% had HFrEF and 93% were receiving beta-blockers. Primary outcome occurred in 21.4% of patients. It was more frequent in patients who had lower peak HR (123 vs 141 bpm, P < 0.001), DHR (47 vs 58 bpm, P = 0.004), chronotropic index (0,57 vs 0,78, P < 0.001), peak VO2 (15.4 vs 16.9 ml/kg/min, P = 0.03) and OUES (1.18 vs 1.39, P = 0.002). Univariate survival analysis showed that the same variables remained as outcome predictors. A chronotropic index <0.6 was associated with an HR 2.7 (IC 95% 1.5 -4.7) to the primary endpoint in the univariate analysis and an HR 3,1 (IC 95% 1,2-7,8) in the multivariate adjusted for sex, age, CKD, DM and use of beta-blockers, remaing as the strongest risk predictor in our sample. Conclusion: A blunted HR response in patients with HF and AF, evidenced by lower chronotropic index, DHR and HR peak, was associated with an increased risk of death or need for heart transplant in our sample. These findings question the real benefit of beta-blocker use in this scenario. Further studies evaluating the reduction or withdrawal of these medications could help to answer our question. 109185 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Correlation between Antenatal Diagnosis and Origin of Critical Congenital Heart Defects in a Neonatal Intensive Care Unit NICOLE DE OLIVEIRA SANTOS1, Giovana Rezende Fernandes Costa1, Jennifer Klassen Boeing1, Luis Antonio Zorzi Santin1, Adriana Saito Jasper2 (1) Universidade Positivo (UP); (2) Associacao Hospitalar de Protecao a Infancia Dr. Raul Carneiro/Hospital Pequeno Principe (HPP) Introduction: Critical congenital heart diseases (CCHD) require intervention as early as possible. The delay in its diagnosis increases the risk of morbidity and mortality in newborns (NB). Prenatal diagnosis of CCHDs is at first done using morphological ultrasound, and then more thoroughly by fetal echocardiography, allowing for a more deliberate management planning of birth conditions with the family and health-care providers. However, these exams are not offered to all pregnant women by the Healthcare System in Brazil. Objective: To correlate the antenatal diagnosis with the origin of newborns admitted for critical congenital heart defects in a neonatal intensive care unit of a tertiary hospital in Curitiba, Parana, Brazil. Methods: This was a retrospective study reviewing medical records covering the period from January 1st 2015 to December 31st 2019 of patients diagnosed with critical congenital heart disease who were admitted to the Neonatal Intensive Care Unit. A descriptive analysis of the collected data was performed. Results: The study included 127 patients. The CCHD type incidence found in our sample was: coarctation of the Aorta (20.5%), transposition of great arteries (15.7%), pulmonary atresia (13.4%), hypoplastic left heart syndrome (11.8%), tetralogy of Fallot (3.1%), anomalous pulmonary vein drainage (3.1%), Ebstein anomaly (3.1%), tricuspid atresia (2.4%), truncus arteriosus (2.4%), double outlet right ventricle (1.6%), aortic stenosis (0.8%) and two or more heart defects combined (22%). Prenatal diagnosis, performed on 41.7% of the patients, showed statistically significant relation with the origin of the NB (p < 0,0001). Curitiba, capital of the state of Parana, had the highest proportion of prenatal diagnosis (69%) when compared to the Greater Curitiba region (25.9%), the countryside region of Parana (25%) and other Brazilian states (50%). Conclusion: Most patients with CCHD weren't diagnosed prenatally and, amongst the NB with a prenatal diagnosis, most were from Curitiba - PR. Due to the available infrastructure in the capital, Curitiba has the necessary technology and professionals qualified to perform diagnosis, scanning protocols and practice related to prenatal screening, suggesting an important role in their implementation. 109188 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Value of Atrial Fibrillation in Progression of Mitral Regurgitation in Rheumatic Heart Disease ALEXANDRE NEGRAO PANTALEAO1, Nayana FA Gomes1, Vicente Rezende Silva1, William AM Esteves1, Marildes Luiza de Castro1, Lucas Chaves Diamante1, Fernando Cunha Ruffo1, Matheus de Oliveira Ferreira1, Luis Felipe Rezende de Almeida1, Maria Carmo P Nunes1 (1) School of Medicine, Federal University of Minas Gerais (UFMG) Introduction: Rheumatic heart disease (RHD) is the leading cause of cardiovascular death in children and young adults, and disproportionally affects middle-income countries. Mitral regurgitation (MR) is the most common valve abnormality in RHD and it is often associated with atrial fibrillation (AF). AF is the most prevalent sustained arrhythmia in RHD and it is a marker of disease severity with poor prognosis. Objective: This study aims to investigate the association between AF and MR progression in patients with RHD. Methods: Consecutive RHD patients with non-severe MR associated with any degree of mitral stenosis were selected between 2011 and 2021. Primary endpoint was progression of MR, which was defined as an increase of one grade in MR severity from baseline to the last follow-up echocardiogram. AF diagnosis was based on a history of permanent AF supported by past 12-lead electrocardiogram (ECG). Diagnosis of new-onset AF in patients with sinus rhythm at baseline was confirmed by 12-lead ECG. Results: 539 patients were included, aged 46.2 +- 12 years, and 83% were women. At a mean follow-up time of 4.2 years (IQR: 1.2 to 6.9 years), 54 patients (10%) displayed MR progression with an overall incidence of 2.4 per 100 patient-years. Patients who had new-onset AF during the follow-up were at risk for progression (adjusted hazard ratio [HR] 2.447, 95% CI 1.035-5.788) and patients with permanent AF were at the highest risk (HR 4.459, 95% CI 2.148-9.631) compared with patients in sinus rhythm. Conclusions: In RHD patients with a full spectrum of MR severity, progression of MR occurs over time, associated with the presence of AF. AF burden either permanent or new-onset AF led to an increased risk of progression of MR. 109194 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cross Sectional Study of Heart Failure Mortality Reported in Brazil between 1999 and 2018 FILIPE ALVES RAMOS 1, ROSANGELES KONRAD2 (1) Catholic University of Brasilia; (2) Hospital Anchieta - Carddio Clinic Introduction: Heart failure is a cardiovascular pathology that presents a high mortality rate. According to the World Health Organization (OMS), 23 million people live with this disease in the world. Hypertension, as well as diabetes and coronary artery disease are the main risk factors for the development of heart failure and are related to their worst prognosis. Objective: Analyzing the evolution of the number of deaths from heart failure in Brazil between 1999 and 2018. Methods: This is a descriptive and quantitative cross sectional study conducted between 1999 and 2018 on the number of deaths from heart failure documented in Brazil. The analyzed data were obtained through the Department of Informatics of the Brazilian Unified National Health System (DATASUS). Results: From 1999 to 2018, 550,969 deaths from heart failure were recorded in Brazil. The mortality rate in 2018 decreased 29.71% compared to 1999. The number of deaths in Brazil in 2018 (26.482 deaths) was 10.32% lower than the recorded in 1999 (29.531 deaths). In relation to race/skin color deaths, it was found that white people 297.198 (53.94%) and pardo people 157.282 (28.55%) were the most affected. In the distribution by age groups there was a higher prevalence of mortality over 80 years: 233.283 (42.34%); followed by 70 to 79 years: 144.164 (26.16%); 60 to 69 years: 89.072 (16.17%); 50 to 59 years: 46.643 (8.46%); 40 to 49 years: 20.871 (3.79%); 30 to 39 years: 8.589 (1.56%) and those under 30: 7.747 (1.41%). There was a 29.71% reduction in the mortality rate for every 100,000 people, when compared to the one registered in 2018 (12.66%) with that documented in 1999 (18.01%). Conclusions: Through the results presented, it is noted that the mortality rate, as well as the number of deaths from heart failure has decreased in Brazil over the years. This reduction is justified by the greater use of beta-blockers and angiotensin-converting enzyme, which reduce the morbidity and mortality associated with heart failure. Add to this, the reduced selection of heart failure as a basic cause of death in the face of other cardiovascular diseases, such as hypertension. In the present study, there was a higher frequency of heart failure deaths among white men over the age 60. 109196 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Study of Morbimortality from Heart Arrhythmia and the Relationship with the use of Chloroquine and Hydroxychloroquine as Treatment of COVID-19 in Brazil LARISSA SILVA FERREIRA1, Larissa Silva Ferreira1, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa (UNIFAP) Introduction: Torsades de pointes is a rare type of ventricular cardiac arrhythmia that is characterized by an increase in the QT interval on the electrocardiogram (ECG). After the beginning of the COVID-19 pandemic, the use of chloroquine and hydroxychloroquine (HCQ) became part of treatment protocols. However, later studies demonstrated the low efficacy of these drugs for the treatment and the increase of cardiovascular risks such as angina, arrhythmias and heart failure. Objective: To analyze the mortality trend due to cardiac arrhythmias in the northern region between the periods of 2020 and 2022. Methods: Epidemiological study with a cross-sectional design of mortality and arrhythmia in Brazil between 2020 and 2022. The investigated data were extracted from the Department of Informatics of the Unified Health System (DATASUS). Results: In the period investigated, 18,741 deaths from arrhythmias were documented in Brazil. The growth in the mortality rate was from 11.64% in January 2020 to 15.62% in January 2022. It was observed that the highest mortality rate occurred in the Midwest region (35.04%). Furthermore, the number of hospitalizations for arrhythmias in this period was 27,887, being higher in the Southeast region, which represents 47.7% of hospitalizations. Regarding deaths by sex, it was found that males were the most affected (15.43%) as well as in the number of hospitalizations (56.03%). In the distribution by age groups, higher mortality was observed in individuals aged 80 years or older (16.83%) compared to those aged 55 to 59 years (14.80%). It was also noted an increase in cases of hospitalization in this period in the age group from 65 to 69 years, representing 53.3% of the total number. Conclusions: Based on the results obtained, there was an increase in cases of hospitalizations and deaths due to arrhythmias in the period studied. This mortality was higher in males and in the age group from 65 years old. Thus, HCQ can prolong the ECG QT interval and can trigger an arrhythmia called torsades de pointes. Thus, the use of this drug during the COVID-19 pandemic may, indirectly, have been one of the aggravating factors in this arrhythmia mortality rate. 109241 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY The Effect of Medicinal Plants in Prevention and Treatment of Cardiovascular Diseases: A Systematic Review LEONARDO YOHAN SANTOS CHUCRE DE LIMA1, Elizama Raquel de Souza Silva1, Bruna Lisboa Nunes1, Isabela Ferreira de Freitas1, Luiz Felipe Leao Lima1, Micandria Yanka Fender Lobato1, Luma Maria Favacho Bordalo1, Fernando Gabriel dos Santos Santiago1, Caio Vinicius Botelho Brito1 (1) Laboratorio de Cirurgia Experimental da Universidade do Estado do Para Introduction: Noncommunicable diseases (NCDs) are responsible for 70% of global deaths and about 45% of those are of cardiovascular origin. In Brazil, 72% of deaths result from NCDs and 30% are by cardiovascular diseases (CVDs). Thus, the importance of finding therapeutical strategies and new pharmacological models is evident. In this context, a great number of traditional herbs which have high anti-oxidative and anti-inflammatory capacities have been referred to as effective and might prove beneficial against CVDs. Objective: To assess the existence of cardioprotective effects in medicinal plants. Methods: This study is a systematic review with meta-analysis through the PRISMA method. Searches were conducted in the MedLine and LILACS databases, through the "Medicinal plants" and "Cardiovascular diseases" descriptors and their synonyms indexed in DeCS/MeSH. Randomised studies, case reports and observational studies published in the last 5 years in english and portuguese were included. Integrative reviews and articles without free full text available were excluded. Research resulted in 290 articles that were filtered for analysis by 4 reviewers. Results: The primary outcomes showed important effects of different medicinal plants over congenital cardiopathies' treatment, highlighting its antiatherogenic potencial and reduction of cardiovascular risk factors, especially through lowering body mass index (BMI), waist circumference and cholesterol levels. Furthermore, as secondary outcomes, it was possible to observe a hypotensive action of Acacia longifolia, Urtica Dioica and Viola Odorata extracts, and the regularization of biomarkers and inflammatory response as a result of citrus flavonoids and polyphenols combination, which improved both lipid panel and flow-mediated dilation in studied patients. Moreover, the use of oils, such as Brazil nuts and coconut combined with epigallocatechin gallate, is effective against lipid peroxidation and decreases risk of CVDs. Conclusions: Medicinal plants are a great alternative for treating and preventing CVDs and might be used to develop future studies for promising medicines. 112393 Modality: E-Poster Scientific Initiation - Non-case Report Category: PSYCHOLOGY Psychological Distress at Work: A Cardiovascular Risk Neglected in Public Safety Professionals SUELLEN KEYZE ALMEIDA LIMA1, Dra. Antoinette Oliveira Blackman1, Beatriz Montenegro Oliveira1, Dra. Solange Lopes da Silva1, Adda Cecilia Batista de Carvalho Vieira1, David Ricardo Bernal Lima Hernandez1, Pedro Henrique Alves Miranda1, Patricia Brito de Almeida Borges1 (1) Centro Universitario do Planalto Central Apparecido dos Santos Introduction: Remarkable changes in the work situation have led to the increasing importance of psychomental and socioemotionally demanding conditions at work. Psychic distress at work can encompass stressful situations and numerous consequences that compromise the worker's lifestyle, including cardiovascular risk. Objective: To understand the main triggers of uneasiness at work and relationships between psychic suffering in public security personnel and the risk of cardiovascular diseases among these professionals. Method: An integrative literature review was carried out in the databases BVS-PSI, Scientific Eletronic Library Online (SCIELO), PubMed/MEDLINE, Google Scholar, UptoDate, PePSIC. Results: This study analyzed the association between work-related behavioral characteristics and the main triggers related to illness, such as load, pace, schedule, work environment, among others. Final Considerations: We present reflections about behaviors adopted by the servers, as tools to their process of getting sick; we also point out aspects to be highlighted in prevention and assistance actions. And it links an immediate alert system for anticipation of care to the health of these servers, because they are getting sick. 109224 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Overview of Fallot Tetralogy Correction Procedures and Variants in Children and Adolescents in Brazilian Regions in 10 Years JULIANA DE ALMEIDA SILVEIRA1, Sara Cristine Marques dos Santos1, Anna Julia Tamiozzo Reis1, Girley Cordeiro de Sousa1, Juliana Alves Costa1 (1) Universidade de Vassouras Introduction: Among the congenital abnormalities, cardiac malformations are the most responsible for death, being the main cause of infant death in first world countries. Tetralogy of Fallot (TF) is the most frequent cyanotic congenital heart disease, with an incidence of 10% of congenital heart defects1. TF consists of four concomitant anomalies, namely: right ventricular outflow tract obstruction (RVOT), sub-aortic interventricular communication (VSD), aortic dextroposition associated with overriding over the interventricular septum and right ventricular hypertrophy. The importance of TF lies not only in its incidence, but also in the severity of symptoms and the effectiveness of surgical correction, especially when performed in childhood. Objective: To analyze the current panorama of Tetralogy of Fallot procedures and variants in children and adolescents performed in Brazil for 10 years and to correlate the current epidemiology with the results obtained. Methods: A systematic review of the literature and an observational, descriptive and cross-sectional collection of data on correction of Tetralogy of Fallot and variants in children and adolescents, available in DATASUS - Hospital Information System of the SUS (SIH/SUS) were carried out for a ten-year period - December 2011 to December 2021 - evaluating the value of public spending, complexity, mortality rate, deaths, permanence and character of care and articles available in Scielo and PubMed. Results: In the analyzed period, 2,777 hospitalizations were observed for the performance of correction procedures for Tetralogy of Fallot and variants in children and adolescents, representing a total expense of R$ 65,165,447.56. The total mortality rate in the 10 years studied was 10.44, corresponding to 290 deaths, with 2011 being the year with the highest mortality rate, 12.99, while 2018 had the lowest rate, 8.16. The Brazilian region with the highest number of hospitalizations was the Southeast with 1,265 hospitalizations, followed by the Northeast region with 627. The Midwest region had the highest mortality rate 20.29, while the Southeast region had the lowest rate, with a value of 7.67. Conclusions: The present study identified that the rate dropped from 8.89 in 2009 to 8.76 in 2019. It is worth noting that the Southeast region, despite having the highest number of hospitalizations, has the lowest mortality rate, evidencing the effectiveness of the services performed. 109230 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Epidemiological Analysis of Mortality from Hypertensive Diseases in Brazil, by Region, from 2009 to 2019 CECILIA RODRIGUES VIANA 1, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Larissa Silva Ferreira1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) UNIVERSIDADE FEDERAL DO AMAPA (UNIFAP) Introduction: Systemic arterial hypertension (SAH) consists of a chronic increase in blood pressure to values greater than or equal to 140 mmHg for systolic pressure and 90 mmHg for diastolic pressure. It is considered a multifactorial condition, which presents important risk factors, such as obesity and sedentary lifestyle. It represents one of the most relevant conditions for the incidence of cerebrovascular diseases. Objective: To analyze the epidemiological aspects related to mortality from hypertensive diseases in Brazil, by region, from 2009 to 2019. Methodology: Cross-sectional epidemiological study of mortality from hypertensive diseases by Brazilian region, during the years 2009 to 2019, from the data analysis from the SUS Hospital Information System (DATASUS). Results: In the analyzed period, Brazil recorded 530,382 deaths from hypertensive diseases, with 29,149 in the North region (5.49%), 165,717 in the Northeast (31.24%), 228,553 in the Southeast (43.09%), 73,711 in the South (13.89%) and 33,252 in the Midwest (6.26%). In relation to deaths by race/color, white individuals were the most affected in Brazil (n = 250,330), however, when analyzing by region, changes in this situation are noted, since in the North region, the predominance was of pardos (66.45%), as well as in the Northeast region (62.2%) and in the Center-West region (48.07%). The Southeast and South regions followed the trend of Brazil with the predominance of the white population, corresponding to 57.39% and 84.85%, respectively. Regarding gender, in Brazil, women were the most affected (53.05%), however, when analyzing by region, there are differences in the North and Center-West regions, in which the male population had the highest rates., 52.83% and 51.56%, respectively. The Northeast, Southeast and South regions maintained the Brazilian trend and their female population was the most affected, representing 53.08%; 53.95% and 54.63% of the total, respectively. Regarding the age group, the population aged 80 years and over is the one that dies the most from hypertensive diseases (n = 222,829) in the country. This holds true in all regions, with the Southeast having the highest number of cases (39.17%), followed by the Northeast (35.44%), South (14.68%), Central-West (5.39%) and North (5.29%). Conclusion: It's concluded that SAH mortality in Brazil presents a heterogeneous aspect when analyzed by region, since, generally, Brazilian prevalence trends were not maintained for all. 109231 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Sex and Obesity Modify the Association of Physical Activity with Heart Rate in Brazilian Adolescents MARIANA EVARISTO LEITE1, Domingos Alves de Santana Neto2, Sarah Mariani Rocha Oliveira2, Anna Mayse Feitosa da Silva2, Ana Beatriz Vaz de Araujo2, Katia Vergetti Bloch2 (1) Universidade Federal de Sao Joao del-Rei (UFSJ); (2) Universidade Federal do Rio de Janeiro (UFRJ) Introduction: Physical activity is defined as any bodily movement generated by the skeletal muscles that increase energy expenditure. During physical activity, the autonomic nervous system promotes changes in the cardiovascular system to compensate for the increased metabolic demand required during the effort, including increased heart rate and stroke volume. Resting heart rate usually decreases with physical conditioning, and the stroke volume increases. Therefore, heart rate can be a marker of physical conditioning that accurately assesses physical activity levels. Objective: The study aimed to analyze the association of resting heart rate with physical activity. We also tested the effect of sex and obesity on this association in Brazilian adolescents. Methods: The Study of Cardiovascular Risks in Adolescents was a cross-sectional, national, school-based study with adolescents aged 12 to 17 years old from public and private schools in municipalities with more than 100 inhabitants. An oscillometric blood pressure monitor assessed heart rate. Leisure-time physical activity was categorized according to the week volume (active >= 300 min and inactive = zero min). Obesity was classified by body mass index (BMI = weight/height2) according to age and sex. Data analysis was performed using Stata 15.0, estimating raw and adjusted linear regression models. Results: A total of 73,399 adolescents were evaluated, of which 49.6% were considered inactive (60.2% were girls and 36.9% were boys). The mean heart rate of the inactive group was 83.4 beats per minute, and that of active adolescents was 79.7 beats per minute, p < 0.001. Adolescents with obesity had higher heart rate than those without obesity (83.7 vs. 81.2 beats per minute, respectively; p < 0.001). Adjusting for age, sex and obesity modified the association of physical activity and heart rate (p < 0.001 and p = 0.03 for interaction, respectively). Conclusion: Active adolescents have lower resting heart rate than inactive ones, indicating a predominance of parasympathetic modulation instead of sympathetic modulation. These results suggest that the physical activity classification adopted in the study reflects the physical conditioning of adolescents and that sex and obesity modify the effect of the relationship between physical activity and heart rate. 109247 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The use of Chloroquine and Hydroxychloroquine in Hospitalized COVID-19 Patients: A Retrospective Analysis DANIELLA NUNES PEREIRA1, Maira Viana Rego Souza-Silva1, Magda Carvalho Pires1, Lucas Emanuel Pereira Ramos1, Maria Aparecida Camargos Bicalho2, Fernando Anschau3, Yara Cristina Neves Marques Barbosa Ribeiro4, Milton Henriques Guimaraes Junior5, Luanna Silva Monteiro Menezes6, Neimy Ramos de Oliveira7, Jose Miguel Chatkin8, Milena Soriano Marcolino1 (1) Universidade Federal de Minas Gerais; (2) Fundacao Hospitalar do Estado de Minas Gerais; (3) Grupo Hospitalar Conceicao; (4) Hospital Metropolitano Dr. Celio de Castro; (5) Hospital Marcio Cunha; (6) Hospital Metropolitano Odilon Behrens; (7) Hospital Eduardo de Menezes; (8) Hospital Sao Lucas da PUCRS Introduction: Despite the evidence of lack of benefit, chloroquine has still been prescribed by some doctors to treat coronavirus disease 2019 (COVID-19) patients. Objectives: To describe and analyze the side effects and outcomes associated with the use of chloroquine and hydroxychloroquine in COVID-19 therapy. Methods: This retrospective cohort of a substudy of the multicentric cohort Brazilian COVID-19 Registry, which included consecutive COVID-19 patients, admitted to 37 hospitals in 17 Brazilian cities, from March to September 2020. A propensity score was used to select the sample, matched by age, sex, cardiovascular comorbidities and hospital. Chi-square or Fisher tests were used to compare categorical variables and the Wilcoxon test for numerical variables. Results: From 7,732 COVID-19 patients, 280 (89.7%) were treated with hydroxychloroquine and 32 with chloroquine (10.3%) and 515 were randomly selected as controls. Demographic data and comorbidities are shown in Table 1. During hospitalization, 3.2% of the chloroquine patients presented side-effects to the medication and 40.0% of them required therapy interruption. Electrocardiography abnormalities were more prevalent in patients using chloroquine than controls (36.5% vs 26.9%). With regards to patient outcomes, patients who used chloroquine/hydroxychloroquine had a higher frequency of admission in intensive care units (45.2 vs. 34.0%, p = 0.002) and mechanical ventilation (34.6 vs. 25.5% p = 0.008). Mortality was not significantly different between groups. Conclusion: Patients undergoing COVID-19 treatment with chloroquine/hydroxychloroquine presented higher frequency of intensive care unit and mechanical ventilation requirement than matched controls who did not use the medications. In-hospital death rates were similar. 109250 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Clinical and Epidemiological Analysis of Critical Congenital Heart Diseases in a Neonatal Intensive Care Unit GIOVANA REZENDE FERNANDES COSTA 1, Jennifer Klassen Boeing1, Luis Antonio Zorzi Santin1, Nicole de Oliveira Santos1, Adriana Saito Jasper2 (1) Universidade Positivo (UP); (2) Associacao Hospitalar de Protecao a Infancia Dr. Raul Carneiro/Hospital Pequeno Principe (HPP) Introduction: Congenital heart disease (CHD) is the most common congenital disease among newborns (NBs). CHDs defined as critical, generally dependent on the ductus arteriosus' permeability, account for around 20% to 25% of heart diseases. The definition of the clinical-epidemiological profile of these patients can help in proposals and optimization of treatments. Objective: Perform an epidemiological analysis of critical congenital heart diseases (CCHDs) in NBs admitted to the Neonatal Intensive Care Unit of a tertiary care hospital in Curitiba/PR. Methods: This was a retrospective study reviewing medical records covering the period from January 1st 2015 to December 31st 2019 of patients diagnosed with CCHDs who were admitted to the Neonatal Intensive Care Unit. Results: The sample consisted of 127 patients. The incidence of diagnoses found is represented in the graph. Sixty-five (51.2%) male and 62 (48.8%) female patients were identified. Regarding gestational age, 0.8% of NBs were born at less than 30 weeks, 7.1% between 30 and 33 weeks, 13.4% between 34 and 36 weeks, 47.2% 37 to 38 weeks and 31.5% over 39 weeks. Considering the clinical outcomes, 38.6% died, of which 73.5% of deaths were due to cardiogenic shock, 24.5% due to septic shock and 2% due to other causes. When relating the type of CCHD with the number of deaths, the mortality rate was higher in cases of hypoplastic left heart syndrome (p < 0.017) and tricuspid atresia (p < 0.027). Conclusion: Within our sample, the main diagnoses were hypoplastic left heart syndrome, coarctation of the aorta, transposition of the great arteries, tetralogy of Fallot, and pulmonary atresia, following what is detailed in literature. No level of significant correlation was found between the type of CCHD and gender and between the type of CCHD and gestational age at birth. There was a statistical significance in the correlation between mortality and the two heart diseases: hypoplastic left heart syndrome and tricuspid atresia, in most cases resulting in death. These data should be evaluated as opportunities to improve care for heart disease. 109256 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Epidemiological Aspects of Congenital Heart Diseases as a Cause of Infant Death in the Northern Region of Brazil between 2016 and 2019 CECILIA RODRIGUES VIANA 1, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Larissa Silva Ferreira1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) UNIVERSIDADE FEDERAL DO AMAPA (UNIFAP) Introduction: Congenital heart diseases (CHD) consist of macroscopic abnormalities of the heart or great vessels and constitute an important cause of infant death, death occurring in live-born children from the moment of birth to an incomplete year of age. These malformations can occur in the first eight weeks of pregnancy, in which the cardiac system begins its formation. The patient may have respiratory and circulatory failure as the main complications resulting from this pathology, which are decisive for the compromise of the child's quality of life. Objective: To analyze the epidemiological aspects regarding infant death due to congenital heart disease in the North region, from 2016 to 2019. Methods: Cross-sectional epidemiological study of infant mortality due to congenital heart disease in the North region between 2016 and 2019, based on the analysis of data from the Hospital Information System (SIH) from the DATASUS database. Results: During the study period, 1,342 infant deaths from congenital heart disease were reported in the North region, which corresponds to 11.9% of the total number of deaths from this cause in Brazil (11,277 deaths). In 2016, the number of deaths was 301 children, in 2019 this figure was 349, which represents an increase of 15.95% during the years analyzed. Regarding deaths by color/race, it was noted that brown individuals were the most affected: 830 (61.85%), followed by declared whites: 354 (26.37%). With regard to maternal schooling, it was observed that mothers with schooling between 8 and 11 years are the most affected (37.77%) by this fatality. In terms of gender, males had a higher number of cases: 705 (52.53%) versus 630 (46.94%) throughout the analyzed period. Conclusions: Based on the data obtained, it can be concluded that the highest incidence of infant deaths from congenital heart disease in the North region occurs in mixed-race male individuals whose mother has between 8 and 11 years of schooling. There was also an increase in the number of cases between 2016 and 2019. 109257 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Association of Myocardial Injury with Mortality in COVID-19 Patients EDUARDO BARROS SCHAUSTZ1, Joao Dario Martins de Mattos1, Andrea Silvestre de Sousa3, Emiliano Horacio Medei2, Denilson C. de Albuquerque1, Olga Ferreira de Souza1, Fernando A. Bozza1, Gabriel C Camargo1, Paulo Henrique Rosado de Castro1, Ronir Raggio Luiz2, Renata Moll-Bernardes1 (1) D'Or Institute for Research and Education (IDOR); (2) Federal University of Rio de Janeiro (UFRJ); (3) Evandro Chagas National Institute of Infectious Diseases (INI) Background: Myocardial injury has been associated with adverse outcomes and mortality in patients with Coronavirus disease 2019 (COVID-19); however, there are still important knowledge gaps regarding its pathogenesis and clinical implications. Aim: To assess the prevalence and mortality associated with myocardial injury in a large population of hospitalized patients with COVID-19. Methods: Consecutive adult patients hospitalized with COVID-19 were prospectively included in a multicenter registry (n = 3246). Troponin levels were measured in the first week of hospitalization (n = 1476) and normalized according to the 99th percentile upper reference limit (URL). Demographic, clinical, and laboratory data were collected, and a logistic regression model was used to quantify the association with the primary outcome. Results: Myocardial injury (troponin levels > URL) was detected in 353 cases (23.9%). Total in-hospital mortality was 10.9% (IC95%: 9,8% - 12,0%). The mortality rate was higher among patients with cardiac injury (22,7% vs 5.5%) and increased for each level of troponin . In-hospital mortality and myocardial injury were associated with older age, reduced oxygen saturation, diabetes, hypertension, heart failure, coronary artery disease, and chronic renal disease, but were not associated with sex. After adjusting for age and comorbidities, a multivariable logistic model showed a higher risk of death in patients with cardiac injury with an odds ratio of 2.99 (95% CI: 2,06-4,36). According to the model, age, oxygen saturation <=93% and diabetes were also independent risk factors for mortality with COVID-19. Conclusions: Myocardial injury was detected in 23.9% of the patients hospitalized with COVID-19 and was an independent predictor of in-hospital mortality. Mortality rate increased for each higher troponin category level. Myocardial injury and mortality were also associated with age, reduced oxygen saturation and cardiovascular comorbidities. 109266 Modality: E-Poster Scientific Initiation - Non-case Report Category: ANTICOAGULATION Fondaparinux Versus Enoxaparin in the Treatment of Obese Patients with Acute Coronary Syndrome BEATRIZ ROCHA DARZE1, Carolina Costa da Silva Souza1, Joao Victor Santos Pereira Ramos1, Queila Borges de Oliveira2, Mateus Santos Viana2, Eduardo Sahade Darze2, Luiz Eduardo Fonteles Ritt2 (1) Escola Bahiana de Medicina e Saude Publica; (2) Instituto Dor de Pesquisa e Ensino, Hospital Cardio Pulmonar Introduction/Background: Fondaparinux is an effective and safe anticoagulant in the treatment of non-ST segment elevation acute coronary syndromes (NSTE-ACS), when compared to enoxaparin. However, due to the underrepresentation of the obese population in clinical trials, the application of these results to obese patients is still uncertain. Purpose: To compare fondaparinux to enoxaparin in the treatment of obese patients with NSTE-ACS. Methods: This is a retrospective cohort study including obese patients (BMI >= 30 kg/m2) admitted with a diagnosis of non-ST segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and treated with fondaparinux or enoxaparin at a tertiary hospital, between 2010 and 2017. The study compared clinical and laboratory characteristics between the fondaparinux and enoxaparin groups using the Chi-square and Mann Whitney tests, when appropriate. The incidence of the primary outcome (death, reinfarction, stroke or major bleeding) was compared between groups and a p-value < 0.05 was used for all analyses. The study complied with the Declaration of Helsinki and was approved by the institutional review board. Results: A total of 335 patients with obesity and NSTE-ACS were included, of which, 238 used fondaparinux and 97, enoxaparin. The mean age was 64 +- 12 and 52.5% were male. The prevalence of diabetes, hypertension, dyslipidemia, previous diagnosis of coronary artery disease, previous stroke and use of an invasive strategy were similar between fondaparinux and enoxaparin groups. The incidence of the primary outcome was 4.2% in the fondaparinux group and 5.2% in the enoxaparin group (p = 0.702). There were no significant differences between groups when the primary outcome components were analyzed separately. The incidence of death, stroke, myocardial infarction, and major bleeding in the fondaparinux and the enoxaparin groups were, respectively, 1.3% vs 3.1% (p = 0.251), 0% vs 1% (p = 0.117), 1.3% vs 3.1% (p = 0.251), 2.1% vs 0% (p = 0.355). Conclusion: In a sample of patients with NSTE-ACS and obesity, there was no difference in the occurrence of the composite outcome (death, stroke, reinfarction and major bleeding) between patients using fondaparinux or enoxaparin. Randomized trials are needed to confirm these findings. 109267 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Analysis of Correction Procedures for Interventricular Communication in Brazilian Regions in 10 Years JULIANA DE ALMEIDA SILVEIRA1, Sara Cristine Marques dos Santos1, Girley Cordeiro de Sousa1, Anna Julia Tamiozzo Reis1, Yasmin Monteiro Mandu1 (1) Universidade de Vassouras Introduction: Interventricular communication (IVC) is defined as the absence of septal tissue, which allows communication between the ventricles. Among the congenital heart diseases, it is the most frequent, corresponding to about 35%. In Brazil, data indicate an incidence variation of 0.6/1000 live births and it is estimated that 28,000 new cases will appear per year, of which 23,000 will require surgical intervention. In view of the above, a more in-depth knowledge about this anomaly becomes, therefore, a subject of great interest not only for its high frequency, high number of hospitalizations and expenses for the health system, but also serves as an alert for the need of more comprehensive research in order to know the possible risk factors and make an early diagnosis. Objective: To analyze the current panorama of CIV Correction procedures performed in Brazil for 10 years. Methods: A systematic literature review and observational, descriptive and cross-sectional collection of IVC Correction data, available in DATASUS - SUS Hospital Information System (SIH/SUS) for a period of ten years - December 2011 were carried out. to December 2021 - evaluating the value of public spending, complexity, mortality rate, deaths, permanence and character of care and articles available in Scielo and PubMed. Results: In the analyzed period, there were 2,951 hospitalizations for IVC Correction procedures, representing a total expense of R$55,801,572.62. The Brazilian region with the highest number of hospitalizations was the Southeast with 1,228 hospitalizations. The region with the highest number of deaths was the Southeast with 79 cases, while the North region had the lowest number, with 6 deaths recorded. The North region had the highest mortality rate (8.96). The Northeast region had the lowest rate, with a value of 5.58. Conclusions: In view of the data, there is a higher prevalence of hospitalizations in the three most industrialized Brazilian regions (Southeast, Northeast and South). On the other hand, emergency procedures have the highest mortality rate. Furthermore, the highest mortality rate occurs in the regions with the lowest prevalence, the North and Midwest regions, and the deaths are higher in the Southeast and Northeast regions. Thus, there is a need to expand data collection in order to improve the current epidemiological analysis. 109272 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hypertension and Diabetes: An Analysis of its Prevalence in Women in a Brazilian State Over a Decade DANIEL DE OLIVEIRA MEIRELES 1, Sara Cristine Marques dos Santos1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Patricia Rangel Sobral Dantas1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: High blood pressure (HTN) and diabetes mellitus (DM) are two common diseases today. Complications of DM and HTN can include chronic kidney disease, cardiovascular, or cerebrovascular disease. The association of these diseases increases cardiovascular risk and morbidity and mortality1. The present study aimed to analyze the current panorama of cases of hypertensive and also diabetic patients in the state of Paraiba for 10 years and to correlate the current epidemiology with the results obtained. Methods: A systematic review of the literature and an observational, descriptive and cross-sectional collection of data on HTN and DM, available at DATASUS - System for registration and monitoring of (HYPERDIA) for a period of ten years - December 2002 to December 2012 - and articles available in Scielo, Lilacs, and PubMed. Results: In the analyzed period, 55,993 follow-up records of patients with HTN and DM were observed, of which 38,103 were female and 17,890 were male. Of the 55,993, 27,486 are considered sedentary, 19,008 of whom are women. Overweight in 25,635 cases. According to the age group, there is a greater number of cases from 55 to 69 years old, with an average of 7,461 cases (obtained through the arithmetic mean of the values shown by DATASUS). There are 14,569 smokers out of the total. Among the total cases, 5,222 patients with previous acute myocardial infarction and 6,513 with stroke were identified. 3,026 cases of diabetic foot were recorded. Counting 1,859 cases of amputation due to DM. Of 55,993 patients, 3,344 have chronic kidney disease. As for risk, 27,784 are considered high risk, 10,217 are very high risk and 17,992 have no calculated risk. Conclusions: From the present study, the prevalence of SAH and DM in women is higher than in men. It is worth emphasizing the need to invest in primary care to control and treat these patients, also preventing new ones. Besides, there is a need for correct notification of procedures, to improve the current epidemiological analysis. 109273 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Peripartum Cardiomyopathy and the Relationship of Oxidative Stress and Prolactin Levels LARA ALIPIO PEDROSA1, Ariana Lacerda Garcia1, Beatriz Ribeiro Coutinho de Mendonca Furtado1, Carolina Goncalves da Cunha Lima1, Gabriella de Figueiredo Falcao1, Lais Nobrega Diniz1 (1) Faculdade de Medicina Nova Esperanca (FAMENE) Introduction: Peripartum cardiomyopathy is a form of dilated cardiomyopathy of uncertain etiology, characterized by reduced left ventricular ejection fraction, which affects women without preexisting heart disease during the last month of gestation or until the fifth month of puerperium. The factors identified as the greatest risk for its development include advanced maternal age, black race, gestational hypertension and family history of cardiomyopathies. Clinical presentation includes signs and symptoms of congestive heart failure with tachycardia, tachydyspnea, edema, orthopnea, swollen jugular veins, and nocturnal cough. Objectives: To discuss the clinical manifestations of peripartum cardiomyopathy, in addition to the link between prolactin levels in the genesis of this cardiomyopathic condition. Methods: This bibliographic review had a qualitative character based on exploratory and selective readings of articles and scientific websites (Sciello, PubMed, UpToDate) referring to the topic in question. Results: The hemodynamic stress of pregnancy on the heart can trigger the clinical manifestation of genetic forms of previously silent cardiomyopathy. Studies show identified evidence of MCP carriers with a family history of cardiomyopathy and a subgroup of patients with mutations in genes related to familial forms of cardiomyopathy. New pathophysiological concepts were recently presented in the literature, involving oxidative stress and prolactin levels in the genesis of MCP. Oxidative stress activates cathepsin D in cardiomyocytes, an enzyme that promotes proteolytic cleavage of prolactin resulting in the 16 KDa fragment, which is a potent factor with pro-inflammatory, antiangiogenic, pro-apoptotic, vasoconstrictor and cardiomyocyte depressant characteristics. In agreement with these findings, inhibition of prolactin secretion with bromocriptine, a dopamine receptor agonist, prevents the development of MCP. Conclusion: Peripartum cardiomyopathy is a condition with several risk factors and without a defined cause. Treatment uses drugs for heart failure in general and the prognosis is still poor. With therapeutic advances, the mortality rate of peripartum cardiomyopathy has decreased, among these, those related to the study of the association of prolactin. Research with a view to clarifying the etiopathogenesis of this disease should be implemented, which may facilitate preventive measures. 109288 Modality: E-Poster Scientific Initiation - Non-case Report Category: ANTICOAGULATION Influence of Obesity on the Safety and Efficacy of Antithrombotic Therapy: A Systematic Review and Meta-Analysis BEATRIZ ROCHA DARZE1, Queila Borges de Oliveira2, Mateus Santos Viana2, Eduardo Sahade Darze2, Luiz Eduardo Fonteles Ritt2 (1) Escola Bahiana de Medicina e Saude Publica; (2) Instituto Dor de Pesquisa e Ensino, Hospital Cardio Pulmonar Background/Introduction: The prevalence of obesity has increased in recent decades and, considering its association with a higher risk of Venous Thromboembolism (VTE) and Acute Coronary Syndromes (ACS), it is necessary to establish an anticoagulation regimen suitable for this group of patients. The obese population is historically underrepresented in clinical trials, so the effect of obesity on the efficacy and safety of antithrombotic treatment is still uncertain. Purpose: To evaluate the influence of obesity on the safety and efficacy of antithrombotic therapy in patients with ACS or VTE. Methods: This is a systematic review and meta-analysis, conducted according to the PRISMA methodology, using the MEDLINE/PubMed, Scielo, Cochrane, EMBASE and Lilacs databases. Articles characterized as randomized, cohort or case-control studies that compared the occurrence of clinical outcomes (mortality or bleeding) between obese and non-obese patients using parenteral anticoagulants for the treatment of ACS or VTE were selected. To assess the risk of bias, the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale were used. Statistical analysis was performed using Revman 5.4 software with relative risk and 95% CI as analytical parameters. Results: Six articles, with a total of 40.939 patients, were eligible for this review, being 3 randomized clinical trials and 3 retrospective cohorts. Of the patients, 87.7% had ACS. The mortality rate was 2.6% (95% CI 2.2% -3.0%) in obese patients and 3.6% (95% CI 3.3% -4.0%) in non-obese patients, while the rate of major bleeding was 6.0% (95% CI 5.6% -6.4%) in the obese group and 6.2% (95% CI 5.9% -6.5%) in the non-obese group. The incidence of major bleeding was similar between groups with RR: 0.90, 95% CI: 0.77-1.04, p = 0.14. The outcome incidence remained comparable when studies were analyzed separately by anticoagulant: enoxaparin (RR: 0.87, 95% CI, 0.70-1.08, p = 0.21) or UFH (RR: 0.96, 95% CI, 0.79-1.17, p = 0.67). The mortality rate, measured by only 2 studies, was lower in obese patients, with RR: 0.71, 95% CI 0.59-0.87, p = 0.0007. Conclusion: In patients treated for VTE or ACS, rates of thrombotic complications, death and bleeding were comparable between obese and non-obese patients, regardless of the antithrombotic used. 109317 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Mavacamtem: A New Perspective in the Treatment of Hypertrophic Cardiomyopathy ANA LIVIA GADELHA XAVIER DA NOBREGA PEREIRA1, Beatriz Gadelha e Xavier1, Bianca Vasconcelos Braga Cavalvante1, Rayanne Alessandra da Silva Barreto1, Leticia Lacerda Burity1, Vinicius Vieira Leandro da Silva1 (1) Faculdade de Medicina Nova Esperanca (FAMENE) Introduction: Hypertrophic cardiomyopathy (HCM) is a heart disease that causes anatomical changes in the cardiac structure, the main one being left ventricular hypertrophy. Mavacamten is a molecule capable of inhibiting myosin ATPase and aims to assist in the treatment of hypertrophic heart disease, reducing contractility, improving diastolic function and promoting a better energetic response in the myocardium. The drug was tested in preclinical studies, demonstrating safety and reduction of obstructive symptoms, in addition to improvement in left ventricular filling pressures. Objectives: This article aims to systematically review the existing literature with the results of the use of the drug mavacamtem for the treatment of hypertrophic cardiomyopathy. Methods: This is a systematic review of the literature indexed between 2018 and 2021, published in the Scientific Electronic Library and PubMed databases. Unfinished and inaccessible articles for free were excluded. Results: The clinical presentation of HCM can vary from asymptomatic to advanced heart failure. Its diagnosis is confirmed by echocardiography and/or vascular magnetic resonance imaging with the observation of left ventricular hypertrophy. Currently, HCM therapy is based on the use of beta-blockers as a first line in symptomatic patients and disopyramide as a second option. Mavacamtem was recently tested in phase three of a randomized double-blind placebo-controlled trial with 251 patients enrolled in the program, where 123 were selected for use of the drug. It was evidenced that 45 patients using mavacamten reached the primary goal against the 22 who reached the use of placebo. Patients using the medication had significant reductions in left ventricular outflow tract obstruction after exercise, a greater increase in pVO2, and improvement in symptoms and quality of life compared to those who did not use the drug. In addition, there was a NYHA class reduction in at least 80 patients. In addition, the drug proved to be tolerable and without important adverse manifestations, being similar to placebo. Conclusion: Currently, the use of macavamten must be associated with previously established pharmacological therapy, in an effective, safe and tolerable way, in order to act directly in the pathophysiology of the disease and to avoid or postpone the need for invasive processes in patients. However, additional studies are needed to determine the best therapy for patients with HCM. 109302 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Accuracy of Clinical Judgment in the Evaluation of Specific Characteristics of Acute Chest Pain Predicting Coronary Artery Disease: A Systematic Review CAROLINA COSTA DA SILVA SOUZA1, Claudio Marcelo Bittencourt das Virgens1, Mateus dos Santos Viana1 (1) Escola Bahiana de Medicina e Saude Publica (EBMSP) Background: Faced with a patient with acute chest pain, the need to rule out the etiology of coronary artery disease (CAD) is substantial due to the high associated mortality. In a scenario of abundant and often unnecessary expenses in the medical field, the need for an initial reasoning to determine which patients need confirmatory tests is highlighted. Because of this, health professionals seek support in the specific characteristics of acute chest pain through the gestalt to determine the pre-test probability of each patient. In view of the wide applicability of this methodology, its validation becomes essential for medical practice. Purpose: To assess the accuracy of clinical judgment in interpreting specific characteristics of acute chest pain for the diagnostic prediction of CAD. Methods: A systematic literature search was carried out through PUBMED, EMBASE, LILACS, SCIELO and CENTRAL databases and manual search. The selected articles were evaluated using the QUADAS-2 tool, and the collected data were used for a qualitative and quantitative analysis of the data, with meta-analysis built according to the fixed effects model, considering the measures of sensitivity, specificity, odds ratio, and diagnostic odds ratio (DOR). The present research was formulated according to PRISMA methodology. Results: Two studies with low risk of bias and good applicability for this systematic review were selected, with a total of 487 patients evaluated in terms of coronary obstruction in an emergency setting. Studies' results were comparable, with values of sensibility and specificity ranging from 0,49 to 0,47 and 0,52 to 0,66, respectively. The calculated DOR was 1.47 (95%CI, 1.02-2.11), p = 0.04. The McNemar test for heterogeneity was 6.91 (p = 0.009). Conclusion: The gestalt of acute chest pain in an emergency context is not a good accuracy method for the prediction of coronary artery disease. New research is necessary to reinforce these findings. 109346 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOGERIATRICS Screening for Sarcopenia in Elderly Patients with Chronic Kidney Disease and Heart Failure ELLEN BEATRIZ SOBRAL2, Carolina Jeronimo Magalhaes3, Maria Eduarda Borges Matias2, Sabrina Barreto Braga Pires2, Carolina de Carvalho Moury Fernandes2, Matheus Dantas Soeiro2, Jessica Myrian de Amorim Garcia1, Francisco Bandeira3 (1) Hospital Agamenon Magalhaes (HAM); (2) Faculdade Pernambucana de Saude (FPS); (3) Universidade de Pernambuco (UPE) Introduction: The reduction of muscle strength, mass and function, known as sarcopenia, has a significant association with physiologic aging process. As the world population has aged, multiple comorbidities such as heart failure (HF) and chronic kidney disease (CKD) are frequent in the elderly, which has correlation with inflammatory factors and sarcopenia. Sarcopenia influences quality of life, morbidity, and mortality. Objectives: Evaluate the screening of high risk for sarcopenia in elderly in-patients with CKD and HF. Methods: Cross sectional observational study from August 2020 to December 2021 in a tertiary cardiology center with in-patients >=65 years. Diagnosis and classification (stage 1 to 5) of CKD was based on CKD epidemiology collaboration equation to estimate glomerular filtration rate (GFR). For this study we established a considered renal disfunction patients with GFR < 60 mL/min/1.73 m2. Sarcopenia screening was performed with Sarc-f and patients with score >5 were defined in a high risk for sarcopenia. Results: A total of 190 patients (53,6% female) were studied. Mean age of 72.9 +- 5.9 years. A total of 49,73% elderly patients had renal disfunction. Stage 3 CKD elderly patients were 31,6% of the population study; 8,9% stage 4; 8,4% stage 5. In elderly patients with both renal disfunction and HF, 36,8% had positive screening for sarcopenia with Sarc-f > 5. The presence of CKD (stages 3 to 5) and HF had no association with the prevalence of high risk for sarcopenia. Conclusions: The screening with Sarc-f in elderly patients with CKD and HF in this study has not shown a significant high risk for sarcopenia. However, screening Sarc-f has providing identification of in-patients at risk of developing sarcopenia, in addition to practicality and specificity in medical practice, which shows the importance of more studies and further analysis. 109543 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Reduction of Cardiac and Vascular Remodeling in Pulmonary Hypertension Induced by Agonist of A2A Adenosine Receptor GABRIEL FONSECA GOMIDE1, Jaqueline S Da Silva1, Bruna Rocha1, Tadeu Montagnoli1, Bruno Eduardo Dematte1, Rodolfo Maia1, Eliezer J Barreiro1, Gisele Zapata-Sudo1 (1) Universidade Federal do Rio de Janeiro UFRJ Introduction: Pulmonary hypertension (PH) is a chronic progressive disease characterized by extensive pulmonary vascular remodeling, leading to right ventricle (RV) hypertrophy and failure. Activation of adenosine receptor A2A (A2A-AR) can limit the progression of PH by attenuating vascular and cardiac inflammation and remodeling. This work aims to evaluate the effects of a new A2A-AR agonist, LASBio-1900, in cardiac and vascular dysfunctions on monocrotaline (MCT)-induced PH in male Wistar rats. Methods: After a single injection of MCT (60 mg/kg i.p.), twelve rats were randomly divided in groups and treated orally with either vehicle or LASSBio-1900. Hemodynamic parameters were obtained by Doppler echocardiography and intraventricular pressure measurement. Pulmonary arteries (PA) muscularization was determined through the percentage of the wall portion positively stained with alpha smooth muscle actin (a-SMA) relative to the total transversal area. Perivascular collagen in PA was evaluated using picrosirius red staining and interstitial fibrosis was measured by obtaining the total collagen area per arteriole area. Evaluation of inflammatory process in perivascular PA was performed by immunohistochemistry to iNOS content in as the ratio of stained area to the arteriole area. Results: PH promotes increased PA vascular resistance, since the ratio of pulmonary acceleration time to total ejection time (PAT/TET) changed from 34.35 +- 0.85 in control rats to 23.17 +- 1.51 in MCT and improved in MCT-LASSBio-1900 to 30.86 +- 2.74 (p < 0.05). LASSBio-1900 reduced RV hypertrophy, as it reduced from 55.4 +- 2.3 to 35.3 +- 5.9% (p < 0.05). PH increased RV systolic and diastolic pressures, 19.21 +- 2.04 and 4.73 +- 1.04 mmHg in control to 51.5 +- 5.2 and 11.9 +- 1.3 mmHg, respectively. LASSBio-1900 recovered RV function reducing systolic and diastolic pressures to 28.4 +- 4.0 and 6.51 +- 0.84 mmHg. The increase in wall thickness observed in MCT 61.70 +- 1.11 to 83.24 +- 1.82% was improved by LASSBio-1900 to 75.24 +- 3.46% (p < 0.05). Perivascular fibrosis in PH rats was 15.06 +- 1.34% and LASSBio-1900 reduced the PA collagen deposition to 8.7 +- 1.4% (p < 0.05). iNOS expression evaluated in control of 4.5 +- 0.3 and MCT of 19.0 +- 0.9% (p < 0.05) in iNOS protein content were observed in PH and LASSBio-1900 reduced to 8.7 +- 1.4% (p < 0.05). Conclusion: A2A-AR activation by LASSBio-1900 improved RV hemodynamics and pulmonary vascular structure in PH, indicating a new alternative treatment. 109378 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Systematic Review of the Efficacy of Anacetrapib in Reducing Cardiovascular Events in Patients with Dyslipidemia or Atherosclerosis BERNARDO BALSAN CAMILLO 1, Carolina Martinez Teixeira1, Rodolfo Balsan Camillo2, Bruna Rocha Mezzomo1, Giuseppe Morales Gentilini1, Joel Soares Dahne1 (1) Universidade Catolica de Pelotas; (2) Santa casa de misericordia de Porto Alegre Introduction: Among the causes of global morbidity and mortality, cardiovascular diseases are among the most prevalent. For the purpose of reducing cardiovascular risk, the use of cholesterol-lowering medications, such as Anacetrapib, has gained prominence in relation to other therapeutic options. Objective: Description of the importance of Anacetrapib in the reduction of cardiovascular events associated with dyslipidemia and atherosclerosis. Method: Systematic review (PRISMA) based on scientific literature from 2011 to 2019, published in PubMed databases. The descriptor used was "Anacetrapib". Articles that show information about the choice of their choice were removed, and those whose content was not related to the proposed topic were removed. 249 titles were found. Of these, 15 were selected, 7 abstracts were read and 7 papers were selected for this study. Result: The results demonstrate that dyslipidemic patients undergoing cholesterol ester transfer protein (CETP) inhibitors, a key protein involved in reverse cholesterol transport, especially Anacetrapib, had a reduction in mortality associated with atherosclerosis and dyslipidemia. The reduction in mortality is due to the significant reduction in LDL, triglyceride and HDL levels in patients who used the drug as a single therapy. Furthermore, in patients on dual therapy, associated with statins, they have a greater ability to reduce cardiovascular events. Although other CEPTs have been analyzed, the only one that has so far not demonstrated adverse effects such as death from cardiovascular and non-cardiovascular causes was Anacetrapib. In addition to being able to be used in replacement therapy for statins, this medication can be used both in patients who do not reach LDL levels adequate for their risk, and in patients who do not tolerate statin therapy. Conclusion: Despite the occurrence of drugs that there are more studies on the subject, and ignoring the high cost factor, Anacetrapib is a drug that seems to reduce death from cardiovascular causes in patients with dyslipidemia or atherosclerosis, without causing significant adverse effects. 109369 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Admissional D-Dimer Level as a Biomarker for Assessment of COVID-19 Prognosis in a University Hospital JOAO PEDRO COSTA DOS SANTOS1, Joao Pedro Costa dos Santos1, Mariana Ranucci da Cunha1, Lucas Narciso Balchiunas1, Pedro Henrique Yukio Miyaji1, Henrique Thadeu Periard Mussi1 (1) Universidade Federal Fluminense Introduction: COVID-19 is a respitarory disease that has a physiopathology highly associated with thromboembolic disorders and complications. Some studies suggest that elevated d-dimer can predict poor prognosis in this patients, although cut-off levels are not consensual yet. Objetives: This study aims to correlate admissional d-dimer levels with the need for endotracheal intubation and mortality in COVID-19 patients. Methods: Retrospective cohort study with 142 patients with laboratorial diagnosis of COVID-19 admited at Hospital Universitario Antonio Pedro. We compared mean serum levels of d-dimer between patients submitted to mechanical ventilation or not and with mortality in this group, searching for the association of this variables, using the t-test for this purpose. Statistical analysis was performed in Microsoft Office Excel 2016 and Jamovi 1.6.23. Results: We enrolled 142 patients with laboratorial diagnosis of COVID-19, 53,5% were male, the mean age was 60,3 years, 62,6% were diagnosed with arterial hypertension and 37,3% with diabetes. The mean admissional d-dimer level in the whole population was 2289 ng/ml. In the patients that needed endotracheal intubation the admissional mean levels were 3275 ng/ml and 1809 ng/ml in those who were not intubated. Besides that, the mean admissional levels of d-dimer in the patients that died were 3556 ng/ml and 1834 ng/ml in those that did not have the same outcome. According to the t-test results, high d-dimer admissional serum levels were associated with the need of endotracheal intubation (Statistic = -3,52; p < 0,01) and with mortality (Statistic = -3,96; p < 0,01). Conclusions: This studie concludes that high admissional levels of the d-dimer showed association with poor prognosis in patiets diagnosed with COVID-19 in Hospital Universitario Antonio Pedro. More studies are needed to define a cut-off point and confirm the association between these variables. 109377 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Probable Association between Body Mass Index and Hypertension in Elementary and High School Teachers GLORIA DE MORAES MARCHIORI1, Gloria de Moraes Marchiori1, Daiane Soares de Almeida Ciquinato1, Braulio Henrique Magnani Branco1, Luciana Lozza de Moraes Marchiori1 (1) Universidade UniCesumar UniCesumar Introduction: Obesity and overweight are an important public health problem in society, due to their growth in all age groups and their association with various chronic diseases, especially arterial hypertension. The school constitutes an important environment in the configuration of the teaching staff's reality of life and aspects related to the conditions and organization of the teacher's work, which have repercussions on the health-disease process. The working conditions of teachers can contribute to the development of lifestyle-related diseases, including obesity and high blood pressure. High sedentary behavior has been associated with abdominal obesity, and high sedentary leisure breaks have been associated with lower chances of hypertension among public school teachers. Objective: The objective of the present research was to compare hypertension with the body mass index (BMI) in a sample of teachers. Methods: This is a cross-sectional study, part of a thematic project, part of a broader research called PRO-MESTRE. The project was approved by the Humana Research Ethics Committee, in which all participants were previously informed about its purpose and procedures and signed the Free and Informed Consent Form. Inclusion criteria included being elementary and high school teachers, being actively teaching and being in charge of a subject in class, working in the classroom for more than 12 months, in addition to not having had a leave of absence for >30 days in the 12 months previous. The sample of elementary and high school teachers, who answered the questionnaire with objective questions to verify hypertension. BMI (kg/m2) was calculated based on self-reported body weight (in kilograms) divided by height (in square meters), with the following classification: <18.5: low weight; 18.5 to 24.99: normal or eutrophic; 25.0 to 29.99: overweight; and 30.0: obese. The BMI calculation and classification followed the National Center for the Prevention of Chronic Diseases. Appropriate statistical tests were applied adopting a significance level lower than 0.05%. Conclusion: In the present study, there was a significant association between hypertension and BMI in the teacher population. These observations can help health professionals in the diagnosis of arterial hypertension in teachers and in the approach of anthropometric factors and other comorbidities in the clinical evaluation of these professionals, considering the lifestyle. 109393 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Epidemiology of Deaths by Congenital Malformations of Cardiac Septa in the North Region in the Years 2014 to 2019 JOSE GUILHERME MELO SILVA1, Eduardo Fernandes de Oliveira1, Newton Pessoa de Oliveira Neto1, Ana Beatriz Estrela de Sa1, Giordana do Nascimento Nunes1, Victor Matheus Costa Cardoso1 (1) Centro Universitario Tocantinense Presidente Antonio Objective: Congenital heart disease is considered the most common malformation and the leading cause of death among birth defects, despite being underdiagnosed in Brazil. The aim of this study was to describe the epidemiological profile of deaths that occurred due to congenital heart septal malformation from 2014 to 2019. Methods: This is a cross-sectional, descriptive and quantitative epidemiological study using data of deaths due to congenital heart septal malformation in the Northern region in the period 2014-2019, which were obtained through the computer department of the single health system (DATASUS). Discussion and Results: According to the age group, most cases of death due to cardiac septal malformation occurred in the first year of life, especially in the first month. Comparing the genders, females were slightly more prevalent than males. Comparing the races/colors, the prevalence occurred mainly in those who considered themselves as brown, followed by white, and thus, gathering more than 90% of the cases of deaths due to congenital malformation of the heart septum. Conclusion: It is evident, therefore, that the research findings point to the importance of an active search for congenital heart diseases in the neonatal period and a greater attention to socioeconomic groups that historically are more exposed. Considering that this is one of the main causes of death in the first year of life. In addition, more comprehensive and detailed research is needed to understand the risk factors and develop preventive plans for some of these disabilities. 109411 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Association between Delayed Door to Ballon Time and "Off-Hours" Primary Percutaneous Coronary Intervention BRUNO CARDOSO SCHMOELLER1, Leonardo Sinnott Silva1, Italo Mattos Rinaldi1, Gabriel Fernando Elias dos Reis1 (1) Universidade do Sul de Santa Catarina (UNISUL) Background: Primary percutaneous coronary intervention (PCI) is currently the therapy of choice for the treatment of acute ST-segment elevation myocardial infarction (STEMI). However, randomized clinical trials have shown that when the door-to-balloon time exceeds 100 minutes, the benefits of PCI over fibrinolytic therapy is drastically reduced or even eliminated. Objective: To verify the association of door-to-balloon time with patients admitted in business hours and non-business hours. Material & Methods: 57 STEMI patients who underwent primary PCI between April and August 2021 were included. Results: The average door-to-balloon time (D2B) found was 132.16 +- 68.96 minutes. For better characterization, the D2B time was converted into a categorical variable and separated into two groups: below 90 minutes (26.30%) and above 90 minutes (73.70%). Patients undergoing primary PCI outside of business hours, at night and on weekends, had a higher prevalence of D2B time over 90 minutes (66.60%), with a statistical difference compared to patients admitted during business hours (33.40%) (p = 0,027). It is easily noticeable that the longer D2B time at night and on weekends are related to logistical issues. Conclusion: The average D2B time found is above what is recommended. It was evidenced that the delayed PCIs are mostly concentrated in non-business hours, which negatively affects the prognosis of treated patients. 109478 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Total Cost Estimate of Acute Coronary Syndrome (ACS) in the State of Piaui in the Period from 2011 to 2020 FRANCISCO ELTON COELHO DA SILVA FILHO1, Giuseppe Marques Alencar1, Lidia Lillian Santos Barbosa2, Antonio Maycon da Silva Sousa1, Carlos Eduardo Batista De Lima1 (1) Universidade Federal do Piaui - UFPI; (2) Centro Universitario UniFacid - UniFacid Objective: To estimate the total cost of Acute Coronary Syndrome (ACS) in the State of Piaui, between January 2011 and December 2020. Methodology: For the calculation of direct adirect cost we obtained the number and cost of hospitalizations for Acute Myocardial Infarction and Unstable Angina in Piaui, for the Unified Health System (SUS) through DATASUS/TABNET as well as the values related to angioplasties and revascularization surgeries. From this, data for the Supplementary Health System (SSS) were estimated based on specific annual coverage rates. To estimate indirect costs they were incorporated due to loss of productivity associated with early mortality and absenteeism in patients belonging to the occupied population. Results: The sum of the amounts of hospitalizations by ACS and the procedures performed in the period (total direct cost) was R$ 178,943,799.06 (U$ 35,189,136.92). The sum (total indirect cost) of the estimated costs for absenteeism and early mortality was R$ 1,176,271,322.60 (U$ 231,312,696.18). Therefore, the total estimated cost was R$ 1,355,215,121.66 (U$ 266,501,833.10). Conclusion: The estimated average annual cost of ACS in Piaui was R$ 135,521,512.16 (U$ 26,650,183.31) and showed a downward trend in the last five years of the period. 109414 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 and Chronic Cardiovascular Diseases: Clinical and Epidemiological Indicators in Adults in Southern Brazil JARBAS RYGOLL DE OLIVEIRA FILHO1, EVA BRENDA SANTOS SILVA1, THIAGO EMANUEL RODRIGUES NOVAES1, TASSO KFURI ARAUJO MAFRA1, JOSSIMARA POLETTINI1, GUSTAVO OLSZANSKI ACRANI1, SHANA GINAR DA SILVA1, RENATA DOS SANTOS RABELLO1, IVANA LORAINE LINDEMANN1 (1) Universidade Federal da Fronteira Sul (UFFS), Campus Passo Fundo, BRASIL. Introduction: The Coronavirus Disease 2019 (COVID-19) still represents a global health problem. It is known that such an infection, caused by Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2), can progress to complex clinical conditions, including Severe Acute Respiratory Syndrome (SARS), requiring hospitalization in the Intensive Care Unit (ICU) and use of ventilatory support. It is also clear that patients with previous cardiovascular diseases, as well as other comorbidities, are at greater risk of developing severe symptoms and progressing to death. Objectives: To identify the prevalence of hospitalization in the Intensive Care Unit (ICU), use of ventilatory support and case evolution in adult patients diagnosed with COVID-19, carriers and non-carriers of chronic cardiovascular diseases (CVD). Methods: Observational study based on data analysis from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) in Passo Fundo, RS. The study population consisted of SARS cases due to COVID-19, confirmed and reported from January 1 to December 31, 2020. Sociodemographic and health data were collected from individuals aged between 20 and 59 years. The use of ventilatory support, admission to the ICU and the evolution of the case (death/cure) were used as outcomes of interest, and the exposure analyzed was the diagnosis of CVD. The prevalence was verified with a 95% confidence interval (95%CI) of the outcomes and their distribution according to the predictor variable (chi-square test, admitting an a error of 5%). Results: The sample consisted of 574 participants, with a predominance of men (58.0%) and aged between 41 and 59 years (69.0%). The diagnosis of CVD was observed in 25.3%. The prevalence of ICU admission was 21.0% (CI95 18-24), use of ventilatory support was 65.1% (CI95 61-69) and 12.2% (CI95 9-12) died. A statistically significant relationship was found between CVD and ICU admission (29.0%, p = 0.002) and use of ventilatory support (77.4%, p < 0.001), but not between CVD and deaths (15.6%, p = 0.051). Conclusions: There was a higher prevalence of ICU admission and use of ventilatory support in adults with CVD, a fact that attests to the greater complexity of managing the COVID-19 patient with CVD. The relationship of angiotensin-converting enzyme 2 - the main gateway of SARS-CoV2 - which is also related to CVD, is evaluated. As for lethality, no statistically significant relationship was identified. 109446 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The COVID-19 Pandemic and its Impact on Deaths from Cardiovascular Causes in Brazi GUSTAVO FIALHO COELHO1, Mariana Moreira Vannier2, Tamara Tamara de Souza1, Caroline Melo Jordao Reis2, Karla Santa Cruz Coelho1 (1) Universidade Federal do Rio de Janeiro campus Macae; (2) Centro Universitario Serra dos Orgaos Introduction: The first confirmed death by COVID-19 in Brazil was on 12th March 2020, in the city of Sao Paulo. From then on, the country's health system was affected by the pandemic with the occurrence of direct and indirect deaths. Therefore, an analysis of the pandemic's impacts on other health aspects such as deaths from cardiovascular causes is necessary. Objectives: Analyze the pandemic's impact on mortality from cardiovascular causes in Brazil, as a whole and at home, using death data from the Civil Registry in 2019, 2020 and 2021. Methods: The Civil Registry Portal was accessed on March 28th 2022 and death data from unspecific (UCC) and specific cardiovascular causes - acute myocardial infarction and cerebrovascular accident (CVA), in the years 2019, 2020 and 2021, referring respectively to the pre-pandemic, 1st year of pandemic and 2nd year of pandemic were collected. Results: When comparing the sequence of years there was a single reduction in deaths from infarction from 2019 to 2020 (-4.28%) with an increase in all other analyzed aspects. From 2019 to 2020 there was an increase in deaths from CVA (0.97%) and UCC (31.17%). While from 2020 to 2021 there was an increase in deaths from infarction (6.40%), CVA (3.55%) and UCC (15.94%). When analyzing deaths at home, there was an increase in all death causes; infarction (4.35%), CVA (26.67%) and UCC (69.89%) from 2019 to 2020 and infarction (4.16%), CVA (4.06%) and UCC (14.65%) from 2020 to 2021. There was also a more accentuated growth in deaths from unspecific than specific cardiovascular causes, especially in deaths at home. Conclusion: Deaths from different cardiovascular causes increased when comparing the pre-pandemic period to the pandemic period and persisted from the first year of the pandemic to the second, almost in its entirety. Deaths from unspecific cardiovascular causes and at home had a significant increase, showing a probable influence of the COVID-19 pandemic on the Brazilian health system. Thus, the pandemic's evolution in different phases and the adaptation of the health system to it, demonstrated an influence on the number of deaths from cardiovascular diseases. New studies should be carried out, analyzing the deaths registered in registry offices and the hospital admissions data. 109430 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Descriptive Analysis of Arterial Stiffness Data in a Cohort of Resistant Hypertensives: A Possible Predictor of Cardiovascular Risk GABRIELA GAMA ZAGNI JARDIM1, Antonio Carlos Eberienos Assad Filho2, Julia Resende de Oliveira2, David Ferreira de Lima Duarte2, Maria Gabriela Pimenta dos Santos2, Paola Pugian Jardim3, Andrea Vaospasse Cocco Faria3, Lilian Soares da Costa4 (1) IDOMED - Universidade Estacio de Sa, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil/Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (2) IDOMED - Universidade Estacio de Sa, Campus Citta, Rio de Janeiro, RJ, Brasil/Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (3) Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (4) IDOMED - Universidade Estacio de Sa, Campus Vista Carioca, Rio de Janeiro, RJ, Brasil/IDOMED - Universidade Estacio de Sa, Campus Citta, Rio de Janeiro, RJ, Brasil/Instituto Estadual de Cardiologia Aloysio de Castro/IECAC Background: It is estimated that the prevalence of resistant arterial hypertension (RAH) is 200 million individuals worldwide. Compared to controlled hypertensives, a higher arterial stiffness is observed, and the measurement of pulse wave velocity (PWV) has been, in addition to being a predictor of vascular stiffness, a prognostic marker and increased cardiovascular (CV) risk, especially in low/medium risk populations. Objective: Descriptively analyze the demographics and PWV findings of an RAH cohort. Materials and Methods: Prospective observational study of a consecutive cohort of RAH, who are part of a cohort of individuals at high CV risk (n 163), followed up at a tertiary cardiology unit in Rio de Janeiro. A questionnaire was applied containing sociodemographic data, CV risk factors, comorbidities, medications in use and therapeutic optimization, in addition to reviewing medical records to collect data from complementary exams performed within 12 months. In this group, casual systolic (SBP) and diastolic blood pressure (DBP), central aortic pressure, amplification index and PWV were measured. Results: Fifty-two individuals with RAH were evaluated. The mean age was 65.3 years (42-85 years) and 53.85% (n 28) were female. The most relevant data found were: 75% dyslipidemia, 75% confirmed coronary disease, 55.7% diabetes mellitus, 5.8% chronic kidney disease, 63.8% reported snoring with 25% untreated sleep apnea. In oscillometric analysis, the mean BP was 130.2 x 82.8 mmHg (SBP 91-220 and DBP 68 x 108 mmHg) and PWV 9.45 m/s (6.3-13.3 m/s). Clinical evaluation showed that blood pressure values were elevated by 28.8% for SBP and/or DBP (n 15) and 55.8% for PWV (n 29), using median values as a standard after adjustment for sex, age, and presence of additional risk factors. Conclusion: The data indicate PWV values similar to those of studies with a RAH population of the same age group, emphasizing that a statistically significant percentage presented high PWV values, even in patients with RAH and controlled BP in oscillometric measurements. Additional studies are needed to demonstrate that PWV can be an independent prognostic marker also in high CV risk individuals, which may contribute to the management and pharmacological adjustment of this RAH population. 109454 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Comparative Analysis between Myocardial Revascularization Procedures using Extracorporeal Circulation by Region between 2018 and 2021 in Brazil MARCIO CESAR RIBEIRO MARVAO1, Marcio Cesar Ribeiro Marvao1, Mariana Kondo Obara2, Alice Barroso Guimaraes2, Lucas Campos Maia3, Teresa Giovanna do Carmo Alves4, Danillo Monteiro Porfirio2, Maria Clara Hollanda Cecim4 (1) Instituto Evandro Chagas (IEC); (2) Universidade Federal do Para (UFPA); (3) Universidade do Estado do Para (UEPA); (4) Centro Universitario do Para (CESUPA) Introduction: Among cardiovascular diseases, coronary artery disease (CAD) has been the leading cause of death in Brazil for half a century. Myocardial revascularization (RM) is the most performed cardiac surgery in the country, and aims to improve the blood supply of coronary arteries that have a narrowed or blocked portion, through the implantation of grafts, which can be performed with or without extracorporeal circulation (ECC). Objectives: To quantitatively analyze data on MR using ECC performed in Brazil from 2018 to 2021 and analyze the percentage rate of surgeries by region and national and regional morbidity and mortality rates. Methodology: Cross-sectional, observational and descriptive study, with data from the Hospital Information System of the SUS IT department (SIH/DATASUS) about MR with the use of ECC, including those in which 2 or more grafts were used, performed between 2018 and 2021. Results: There were 67,122 hospitalizations for the procedure studied, with a peak in 2019 (28.7%) and concentrated in the Southeast (42.9%) and South (31.9%) regions. The North region had the lowest value (3.9%). There were 4,003 deaths, with the Southeast region presenting the most expressive amount (39.5%), followed by the South region (32%). The North region presented the lowest numbers (5.5%). The national mortality rate was 5.64 in 2018 and 5.53 in 2019 (a drop of 1.9%), however, during the period of the pandemic, there was a recorded value of 6.51 in 2020 (an increase of 18% compared to 2019). Taking into account the relative mortality rate in the period, the Central-West and North regions had the highest indicators (10.6 and 8.48, respectively). Conclusion: There were 67,122 hospitalizations for coronary revascularization surgery, mainly in the Southeast and South regions, with the lowest rates in the North region. These data may be related to the availability of resources and the greater number of specialized centers in the richest regions. A total of 4,003 deaths were recorded, with the Southeast and South presenting the highest values, which may reflect the number of procedures being proportional to the number of deaths. However, when analyzing relative mortality, the Midwest and North regions led, which implies that there are other factors that increase mortality in these places. During the COVID-19 pandemic, there was an 18% increase in the death rate, suggesting that there may be a relationship between Sars-Cov-2 and CAD complications. 109492 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Analysis of Hospital Admissions and Mortality Rate Due to Cardiac Insufficiency Amongst Elder Patients in Brazil's Regions from 2009 to 2019 IVAN CUOCO SAMPAIO1, Israel Figueira Lemos1, Ingrid Jade Muniz Wanderley1, Joao Lucas Silva Sales1, Juliana de Sousa Tavares1, Luiz Carlos Figueiredo Filho1, Luma Maria Favacho Bordalo1, Maria Eduarda Dantas da Veiga1, Mariana Lassance Maya Palheta1, Paula Larissa Baia Lima1, Rafael Augusto Silva Cabeca1, Ivan Cuoco Sampaio1 (1) Universidade do Estado do Para Introduction: Cardiac insufficiency, also known as heart failure, occurs when the heart cannot pump strongly enough to make sufficient blood reach the entire body, causing several secondary effects on patients, including death. Recently, an increase in the number of cases and mortality related to this pathology has been observed, especially amongst the elderly, due to their vulnerability to this disease because of their age. Objective: Carry out a comparative analysis of death and hospital admission numbers on elderly people, caused by Cardiac Insufficiency in Brazil's regions. Method: This is a quantitative-focused, retrospective cross-sectional study which uses the Brazilian public health system hospital database ("Sistema de Informacoes Hospitalares do SUS - SIH/SUS"), alongside ICD-10: Cardiac Insufficiency. The data searched refers to elder patients - 60 years or more - who were hospitalized or died between the years 2009 and 2019 in the five Brazilian regions. Results: Regarding the data collected, there was a slightly higher frequency of female hospitalization (50.5%) compared to male (49.5%). The Southeastern Region concentrated the highest number of hospitalizations (41.5%), followed by the South (23.6%), Northeast (22.7%), Midwest (7%) and North (5%). The age group that accumulates the highest number of hospitalizations is 70 to 79 years (36.9%), followed by 60 to 69 years (32.8%), finally, 80 years and more (30.1%). In total, 259.416 patients died due to Cardiac Insufficiency. The Brazilian region with most death rates was Southeast (47.1%), followed by Northeast (24.1%), South (18.1%), Midwest (5.9%) and North (4.8%) regions. The age group that concentrated the most mortality was 80 years or more (52.8%), followed by 70 to 79 years (29.2%) and 60 to 69 years (18.0%). Conclusion: According to the data collected, Southeast region has the highest number of admissions and deaths regarding Cardiac insufficiency, this happens due that region's population density. Also, as patients grow older, more female patients suffer from this disease. It has been shown that even though the South has the 2nd highest number of hospital admissions, the Northeast possesses the 2nd highest mortality, possibly due to demographic density or poor infrastructure of the public health system, when compared to the South region. 109472 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Stratification of Patients Care at a Secondary Health Service LAURA MINELLI CANTOIA1, Isabella Molina Silva1, Claudia Helena Cury Domingos1 (1) Universidade de Ribeirao Introduction: Cardiovascular Diseases (CVD) are the leading cause of death in Brazil and worldwide. In Brazil, CVD continue to be the main cause of death and hospitalizations in the country, reaching the mark of 31% of deaths in the adult population. Risk factors for CVD have been in previous work from the Framingham Heart Study. In Brazil, the prevalence of these cardiovascular risk factors (CV) shows regional variation and an inverse relationship between socioeconomic status and cardiovascular mortality. Objectives: Due to the impact of CVD on public health, nationally and internationally, this study aims to know the variables that make up the CV risk of patients, in order to stratify them into risk groups, identifying the most vulnerable patients and those with greater need for care attention. Methodology: This is an observational, descriptive and transversal study. Data from medical records of patients being followed up at cardiology outpatient clinic of a secondary hospital in Ribeirao Preto, Sao Paulo, between 2019 and 2022 were included. Individuals aged between 49 and 95 years were included in the study. For CV risk stratification, the "Cardiovascular Risk Stratification Calculator" of the Brazilian Society of Cardiology was used, which allows inferring the patient's prognosis over the next 10 years. Results: A total of 182 medical records of patients undergoing follow-up at the outpatient clinic were studied. For CV risk stratification, the following variables were used: Presence of Clinical or Subclinical Atherosclerotic Disease, Type 1 or Type 2 Diabetes Mellitus, Gender, Age, Arterial Hypertension, Smoking and Dyslipidemia. Of the study patients, 40 of them (22%) were classified as very high CV risk, 124 (68.1%) as high CV risk, 13 (7.1%) as medium CV risk and 5 (2.7%) as low CV risk. Conclusion: Cardiovascular risk stratification allows establishing a more assertive and individualized clinical approach. When analyzing the clinical profile of these patients, it is observed that most are at high risk for cardiovascular events and, therefore, will need a multiprofessional approach for adherence to lifestyle changes and prescription of adequate drugs, in order to reduce the chances of CV events in the next 10 years. 109490 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Heart Failure Morbidity in the North of Brazil from 2017-2021: An Epidemiological Study ADRIA RAYANE LIMA CASCAES1, Ana Josefina Goncalves Salomao2, Antonia Evelyn Albuquerque Costa1, Fernando Maia Coutinho3, Vinicius Queiroz Silva1 (1) Universidade do Estado do Para UEPA; (2) Centro Universitario do Estado do Para CESUPA; (3) Universidade Federal do Para UFPA Background: Cardiovascular diseases are one of the main causes for mortality and hospitalizations worldwide. In Brazil this tendency started in the decade of 1960 and persists until nowadays. The increasing incidence of admissions by heart failure from 2008 to 2018 shows the importance of analyzing the scenario of morbidity in the north of Brazil. Objective: Review the epidemiological profile of heart failure morbidity between 2017-2021 in the north of brazil. Methods: Epidemiological and Ecological descriptive study. Data extracted from the Department of Informatics of the Unified Health System (DataSUS) through health information (TABNET), considering age, sex, race and year the patients receive care. Results: From 2017 to 2021, there were 50,264 hospitalizations for heart failure in the northern region of Brazil. The highest number occurred in 2018 (11,255), followed by 2019 (11,078) and 2017 (10,961), the lowest occurred in 2021 (8,176). Analysing distribution by sex, the predominance of admissions was among men with a range of 29,449 (58%), compared to women who total around 20,815 (41%), demostraiting that heart failure affects more in men's health. The prevalence of the disease can be considered of great importance in the state of Para, where the number of hospitalizations was the highest in the North, totaling 22,161 during the study period. Para was not the one with the lowest mortality rate, obtaining about 10%, in comparison, the state of Acre had a much lower number of admissions (1,655) and the highest mortality rate among Brazilian states (17.95%). Ranging from younger than 1 to older than 80 years, elderly between 70 and 79 years old, followed by those between 60 and 69 years old, showed the higher incidence of heart failure hospitalizations. In opposition, the younger ones have the lowest values, and it was observed that hospitalizations begin to decline considerably from those under 30 years of age. In relation to color/race, the prevalence occurs in people self-declared to be brown (30,915) and to a lesser extent in indigenous people. Conclusions: The epidemiological profile identified a higher alarm on the populations of men, self-declared to be brown, elderly between 70 and 79 years and residents of the state of Para. Therefore, these groups need to be a distinct focus of the health system attention to the prevention of this morbidity, for a more effective management of resources and better care for patients with their specificities. 109494 Modality: E-Poster Scientific Initiation - Non-case Report Category: ANTICOAGULATION Telemedicine-Based Management of Oral Anticoagulation: Impact on Thromboembolic and Bleeding Events - Systematic Review and Meta-Analysis LAURA CAETANO DE SA 1, Leticia Santos Dias Norberto Ferreira1, Alair Junio Rocha Arantes2, Hebatullah Abdulazeem3, Ishanka Weerasekara4, Raissa Carolina Fonseca Candido2, Rodrigo Lanna de Almeida5, Samuel Rosa Ferreira2, Tati Guerra Pezzini Assis2, Thais Marques2, Isabela Muzzi1, Milena Soriano Marcolino1 (1) Telehealth Center, University Hospital, Universidade Federal de Minas Gerais; (2) Medical School and University Hospital, Universidade Federal de Minas Gerais; (3) Department of sport and health sciences, Technical University of Minich, Germany; (4) School of Health Sciences, College of Health, Medicine and Wellbeing, The University of Newcastle, Australia; (5) Laboratory of Respiratory Physiology, University of Brasilia Oral anticoagulation is the cornerstone treatment of several cardiovascular diseases, and due to its large applications, different e-health strategies have been proposed and implemented to support the management of such treatment. However, data on the effect of e-health-based anticoagulation management on clinical outcomes are very scarce. Therefore a summary of the best available evidence on the topic is warranted and very appropriate for the current moment, due to the explosion in adoptance of telehealth strategies during COVID-19 pandemic. Our goal was to systematically review the evidence on the impact of telemedicine-based management of oral anticoagulation therapy (OAT) compared to usual care (UC) on thromboembolic and bleeding events. Medline, EMBASE, Cochrane library, LILACS and Google scholar databases were searched from inception to September 2021 for randomized controlled trials (RCTs) comparing telemedicine to UC for OAT management in adult outpatients and reporting any of our outcomes of interest: total thromboembolic events (TTE), major bleeding (MB), mortality or time in therapeutic range (TTR). Risk of bias of included studies was assessed using the Cochrane risk-of-bias tool. Dichotomous outcomes were pooled as relative risks (RR) and continuous outcomes as mean differences (MD), using random-effects models. Regarding the results, twenty-seven RCTs were included, comprising 27 758 patients. Atrial fibrillation and venous thromboembolism were the most common indications for anticoagulation. Different telemedicine strategies were evaluated, such as electronic algorithms for anticoagulant dose adjustment, self-testing and self-management of anticoagulation with remote support, mobile applications for OAT management, among others. Telemedicine resulted in similar rates of TTE (9 studies, RR: 0.88 95% CI: 0.73, 1.06; I2: 0%), MB (9 studies, RR: 0.94, 95% CI 0.82, 1.07; I2: 0%) and mortality (10 studies, RR: 0.98, 95% CI 0.83, 1.17; I2: 0%), when compared to UC, and in slightly improved TTR (15 studies, MD: 2.76, 95% CI 0.37, 5.15; I2: 91%). Concluding, telemedicine-based management of OAT appears to be at least as good as UC when it concerns clinical outcomes, and may be slightly better in regard to quality of anticoagulation, although the confidence in those estimates was moderate or low. 109509 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Hospitalizations by Myocardial Infarction in Northern Region of Brazil: A Ten Years Analysis ADRIANO LEITAO DE ALMEIDA1, Ana Carolina de Sousa2, Carlos Eduardo Alexandre Silva2, Vivian de Lima Brabo1, Larissa da Silva Cambraia1 (1) Universidade do Estado do Para; (2) Universidade Federal do Para Introduction: Acute myocardial infarction (AMI) is defined as the presence of acute myocardial injury associated with the clinical manifestation of ischemia. In Brazil, from 1996 to 2016, the North region was the second region with the highest growth in the mortality rate from AMI. Objective: To describe the epidemiological data regarding acute myocardial infarction hospitalizations in northern region of Brazil between 2012 and 2021. Method: This research is a cross-sectional descriptive study, carried out under a quantitative approach. Data was collected on the website of Hospitalar information system (SIH), from Brazil's healthcare information department, including the hospitalizations on patients living in north region from 2012 to 2021. This study evaluated the number of hospitalizations and its mean length of stay, which were compared by state, gender, age group, race/ethnicity and character of care. The data was analyzed using Microsoft Office Excel 2017 software. Results: During the period studied, there were a total of 45890 cases of hospitalizations for AMI, with emphasis on the year 2021, which represented about 13.23% of all hospitalizations, with a mean length of 8.2 days. The state of Para held the higher hospitalization rates, with 19075 cases (41.57%). The highest number of hospitalizations for AMI occurred between 60 and 64 years old, with 7170 cases (15.62%), however, the longest mean length of stay was in the 65-69 age group, lasting 8.8 days. Men had more hospitalizations due to AMI than women, with 69% of cases, as well as a longer permanence time on hospital, with 8.3 days. In people of brownish color, representing 65.79% of hospitalizations for this disease. Regarding the character of care, urgency was the predominant one, with 86.77% of the total hospitalizations. Conclusion: Thus, this study found higher hospitalizations of AMI on brown men above 60 years old who lived in State of Para, admitted on urgency care. The longer permanence time among advanced age men might suggest a higher morbidity on this group. During the pandemic, the number of hospitalizations was initially stable, however had a significant increase in 2021, which differ from other studies that reported a decrease on hospitalizations due to bigger demand on COVID-19 management, so that could be explained by the allocation of beds initially created for COVID when the incidence decreased, although this relation can be better evaluated on future studies. 109514 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Complication of Decompensated Heart Failure in COVID-19 Hospitalized Patients GABRIELA SILVA SANTOS1, Gabriel Barbosa Figueira dos Santos1, Rafael Alexandre Meneguz-Moreno1, Gilberto Andrade Tavares1, Viviane Correia Campos1 (1) Universidade Federal de Sergipe (UFS) - Campus Lagarto Introduction: Patients hospitalized with COVID-19 and heart failure (HF) have higher in-hospital mortality and complications. Besides, HF as a risk factor for severe SARS-CoV-2 infection could be a complication triggered by COVID-19. OBJECTIVE To analyze the complications developed during hospitalization of patients with COVID-19 and HF. Materials and Methods: It was a retrospective study based on review of electronic medical records of adult patients admitted to the Respiratory Disease Unit (RDU) of a unique hospital from northeast Brazil with RT-PCR reagent for SARS-COV2 and HF diagnosis according to the Framingham criteria. Patients were divided into two groups, one with acute heart failure (AHF) and the other with acute chronic heart failure (ACHF), regarding if they presented with HF for the first time or if they already had this diagnosis, respectively. We have analyzed the comorbidities, complications and mortality between groups and complications according to New York Heart Association (NYHA) functional class and mortality as a hard outcome. Results: The sample consisted of 77 participants, 59.7% (n = 46) male, age 67.1 +- 16.4 years, 33.8% (n = 26) with AHF and 66.2% (n = 51), ACHF. The AHF group had as previous comorbidities mostly diabetes (pdee = 0.019) and chronic lung disease (p = 0.017). There was no difference regarding complications and mortality among the groups. Those with NYHA classification IV and positive SARS-COV2 had an increased risk of developing shock (p = 0.001), cardiopulmonary arrest (CA) (p = 0.01), acute respiratory distress syndrome (ARDS) (p < 0.0001), bacteremia (p = 0.008), hemorrhage (p = 0.04), and liver damage (p = 0.04). In-hospital mortality rate was 39% (n = 30). Mortality was higher in patients who presented as complications: shock (p < 0.0001), CA (p < 0.0001), pneumonia (p = 0.009), ARDS (p < 0.0001), bacteremia (p = 0.0003), hemorrhage (p = 0.02), anemia (p = 0.02), cardiac arrhythmia (p = 0.03), and liver damage (p = 0.04). Conclusion: NYHA functional class IV HF and COVID-19 have a higher risk of developing complications and death during hospitalization, especially when they develop pneumonia, ARDS, shock, CA, anemia, hemorrhage, arrhythmia, liver damage, and/or bacteremia. 109698 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Impact of COVID-19 Pandemic on Admission Rates for Acute Myocardial Infarction and on Management with Coronary Artery Bypass Graft Surgery Through Brazil's Public Health Care System LARISSA DE OLIVEIRA BELTRAO1, Beatriz Ximenes Bandeira de Morais1, Maria Leticia Garrote Bulhoes2, Leticia Ferreira Leal3, Catiane Kelly Schaefer4, Isabela Torres Castro1, Vauma Garrote Bulhoes Barros5, Rafael Jose Coelho Maia6, Maria de Fatima Nunes de Oliveira Mesquita6 (1) Faculdade Pernambucana de Saude; (2) Universidade Estacio de Sa; (3) Universidade de Pernambuco; (4) Universidade de Santa Cruz do Sul; (5) Hospital do Coracao de Alagoas; (6) Hospital Agamenon Magalhaes Background: Acute Myocardial Infarction (AMI), is the major cause of death worldwide, having Coronary Artery Bypass Graft (CABG) Surgery as a therapeutic option. In 2020, with the outbreak of the COVID-19 pandemic, there was a decrease in the number of patients admitted for AMI symptoms, as well as in the number of CABGs. Objective: This study aims to demonstrate the impact of the COVID-19 pandemic changed the main indicators of hospitalizations of patients with AMI in hospitals of the Unified Health System (SUS) in Brazil, their length of stay, mortality rate, number of CABGs, correlation with sex, age and condition of the procedure and hospital stay, and if there is a tendency for return to normality. Methods: This is a descriptive, cross-sectional study conducted using data from SUS Data Transfer Service, about hospital admissions for AMI and CABGs performed between 2019 and 2021. We analyzed the numbers of admissions and procedures undertaken, as well as, percentage reductions in each year across subgroups. Results: 132,173 patients with AMI were admitted to SUS hospitals in 2019, decreasing by 23,95% in 2020, totaling 129,637. The following year it reduced by 13,25%, amounting to 125,916 patients (Tab1). This decrease was proportional between genders and was more prevalent between 50 and 70 years of age. Additionally, the amount of CABG decreased by 1.92% from 2019 to 2020 and 2.87% in 2021. It was accompanied by a decline in the length of hospital stay in 2020 (11,3 days), when compared to 2019 (11,85 days), followed by an increase in 2021 (11,6 days). Furthermore, there was a slight increase in the mortality rate of patients undergoing CABG, both elective and emergency. In 2019, this rate was 5.95, increasing to 7.11 in 2020 and decreasing to 6.84 in 2021. Conclusions: Hospitalizations for AMI continue to decrease at lower intensity, showing a reduction of almost 50% in the trend of previous year, which leads to belief in a full recovery, if this trend continues, in 2022 or 2023. In CABG, we have a continued decrease, however with signs of an imminent recovery in mortality rate and days of hospitalization. 109516 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Primary Percutaneous Coronary Intervention During Off-Hours: One Decade of Experience from a Tertiary Cardiovascular Centre PEDRO HENRIQUE TORRES TIETZ1, Filipe Cirne1, Marcia Moura Schmidt1, Cristiano de Oliveira Cardoso1, Alexandre Schaan de Quadros1 (1) Instituto de Cardiologia do Rio Grande do Sul (IC-FUC RS) Introduction: The gold standard treatment for ST elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (pPCI), but the clinical impact of performing pPCI off-hours is controversial. Objectives: To compare characteristics and major adverse cardiovascular events (MACE) of STEMI patients submitted to pPCI performed off-hours versus on-hours in a reference cardiology center. Methods: Prospective cohort of patients who underwent pPCI for STEMI from 2009 to 2019 in our institution. Patients treated off-hours were compared as to baseline characteristics and short and long-term events. Clinical events were assessed by Kaplan Meier survival curves and Cox regression analysis. A p value <0.05 indicated statistical significance. Results: 2560 patients were treated off-hours and 1876 patients treated on-hours. Most of the baseline characteristics were well balanced between the groups, including similar door-to-balloon times (70min. x 69min; p = 0.15). Patients treated off-hours had a higher thrombus burden (49.6% x 45.5%; p < 0.01). Radial access was more frequently used off-hours (62.1% x 57.6%; p = 0.01). Procedural success (95.7% x 96.4%; p = 0.21) and peri-procedural complications were similar between the groups(p = 0,97). The off-hours groups had higher rates of MACE at 30 days (10.2% x 8.5%; p = 0.04) and 1 year(15.4% x 13.1%; p = 0.03), as well as higher rates of death at 30 days(7.8% x 6.1%; p = 0.03) and 1 year(11.1% x 9.0%; p = 0.02). No statistically significant differences in ischemic events were seen. Conclusion: In our institution, clinical characteristics, door-to-balloon time, pPCI results and short and long-term ischemic events of STEMI patients treated on and off-hours were similar, but off-hours patients presented higher mortality. 109521 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Profile of Hypertrophic Cardiomyopathy Patients in a Cardiogenetic Unit ANTONIO GUILHERME CUNHA DE ALMEIDA1, Braulio Cruz Melo1, Emerson de Santana Santos1, Joao Victor Andrade Pimentel1, Beatriz Luduvice Soares1, Julia Souza Diniz1, Joao Paulo Dias Costa1, Giovanna Medeiros Resende2, Irlaneide da Silva Tavares1, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa1, Joselina Luzia Menezes de Oliveira1 (1) Universidade Federal de Sergipe; (2) Universidade Tiradentes Introduction: Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disease in the world. The diagnosis is made by echocardiography and cardiac magnetic resonance (CMR), and its genetic etiology is defined as pathogenic variations in sarcomeric genes causing left ventricular hypertrophy without any other plausible etiology. Methods: A prospective study was conducted with patients referred to our cardiogenetic outpatient service between January 2021 and March 2022. Patients who met the American Heart Association hypertrophic cardiomyopathy diagnostic criteria had DNA sequenced using Next-Generation Sequencing technique. Statistical analysis was performed using R software version 4.0.1. Objective: To describe the population of patients under investigation for HCM. Results: A total of 74 patients were referred and 52 (70.2%) met HCM diagnostic criteria and had a mean age of 49.7 +- 18.9 years and 71.2% were men. A family history of sudden cardiac death was present in 59.6% patients. Beta-blocking agents were the most commonly used medications (44.2%); 7.7% of patients reported having an implantable cardioverter-defibrillator (ICD). Palpitations were the most reported symptom (69.2%). Rest echocardiogram showed a mean septum wall thickness of 16.6 +- 6.6 millimeters. CMR showed a maximal wall thickness of 17.4 +- 7.4 millimeters. 38.4% of patients had a pathogenic variant in gene panel, 70% of those presented pathogenic sarcomeric variants and the 30% presented a pathogenic variant of a phenocopy. Conclusion: The present study corroborates previous findings. Genetic testing has enabled the distinction between HCM and its phenocopies and accurate genetic counseling for the patients' families. 109522 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Overview of Coronary Angioplasty Procedures with Stenting in the City of Vassouras in 10 Years JULIANA DE ALMEIDA SILVEIRA1, Sara Cristine Marques dos Santos1, Daniel de Oliveira Meireles1, Julia Bardela de Oliveira1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Isabela Costa Linhares1, Joao Paulo Nora Munoz1, Anna Julia Tamiozzo Reis1, Anderlucia Correa Guedes1, Girley Cordeiro de Sousa1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Coronary angioplasty is a procedure performed by percutaneous coronary artery revascularization, decreasing myocardial ischemia. Technically, access is via a percutaneous artery, without the need for a thoracotomy. Stent device implantation was used most of the time. The present study aimed to analyze the current panorama of coronary angioplasty procedures with stent implantation performed in Vassouras - Rio de Janeiro, for 10 years and to correlate the current epidemiology with the results obtained. Methods: A systematic literature review and an observational, descriptive and cross-sectional collection of data on coronary angioplasty with stent implantation, available at DATASUS - SUS Hospital Information System (SIH/SUS) for a period of ten years - December 2008 to December 2018 - evaluating the value of public spending, complexity, mortality rate, deaths, permanence, and character of care and articles available in Scielo, Lilacs, and PubMed. Results: In the analyzed period, 1,675 hospitalizations were identified for the performance of coronary angioplasty procedures with Stent implantation, representing a total expenditure of R $ 8,086,346.37, with 2018 being the year with the highest number of hospitalizations (263) and the year of 2008 with the lowest number of hospitalizations (6). With 2018 as the year responsible for the largest amount spent during the period (R $ 1,173,571.59). Of these admissions, 1,025 were in private. Of the total procedures, 1,112 were performed on an elective basis and 563 on an urgent basis, with 1,675 being considered highly complex. The total mortality rate in the 10 years studied was 1.73, corresponding to 29 deaths, with 2011 being the year with the highest mortality rate, 4.17, with 8 deaths while 2015 had the lowest rate, 0,72, with 1 death. The mortality rate for elective procedures was 1.08 compared to 3.02 for urgent procedures. The average total hospital stay was 2.3 days. Conclusions: It can be observed, from the present study, that there was an increase in the performance of the coronary angioplasty procedure with Stent implantation in the period of 10 years, starting in 2008, accompanied by a reduction in the number of deaths, showing the treatment success. Besides, there is a need for the correct notification of procedures, aiming to improve the current epidemiological analysis. 109529 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY 22Q11 Deletion Syndrome (Digeorge Syndrome/Velocardiofacial Syndrome) and its Correlation with Conotruncal Type Congenital Heart Diseases WALDEMIR FERRARI JUNIOR1, Leonardo Nunes Sanson1, Mariana Castro Pires1, Capitulino Camargo Junior1, Vitor Reis de Souza1, Rafael Fabiano Machado Rosa1, Julio Pasquali Andrade1, Mirian Francine Favero1, Laura Peroni Baldino1, Diego Seibel Junior1, Pedro Enrico Ventura1, Maiquel Andre Teixera1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre Introduction: Congenital heart diseases (CHDs) represent an important public health problem. Although its etiology is not well understood, the 22q11 deletion syndrome (22q11DS) stands out among its known causes, also known as DiGeorge syndrome/Velocardiofacial syndrome. Objective: The aim of this study was to verify the frequency of 22q11DS among patients with a conotruncal CHD. Methods: The sample consisted of a prospective and consecutive cohort of patients in their first hospitalization in a cardiology intensive care unit (ICU) of a pediatric hospital, during a period of 1 year. An evaluation form was filled out for each patient with the collection of clinical data. ALL of them also underwent high resolution karyotype and 22q11 microdeletion investigation using the fluorescent in situ hybridization (FISH) technique. The classification into conotruncal defect was performed by a collaborating cardiologist based on the results of echocardiograms and catheterizations, and also the surgical descriptions Results: Of all patients with CHD, 52 (25.1%) had a conotruncal defect. Thirty-two were male and their ages ranged from 1 day to 10 years (48% <1 month). The main reason for hospitalization was cardiac surgery (76.9%). The most observed CHD was tetralogy of Fallot (TOF) (40.4%). There were no cases of interruption of the aortic arch. Karyotypic abnormalities were observed in 5 patients (9.6%); however, none of them had 22q11DS. The analysis by the FISH technique could be performed successfully in 51 patients, and the 22q11 microdeletion was identified in 2 cases (3.9%) (both with TOF). Conclusions: The frequency of 22q11DS verified in our study was similar to studies that found values ranging from 4 to 15% and different from others that detected rates between 17 and 48%. These differences seem to be related, especially, with the method of patient selection adopted in the studies. Patients with 22q11DS often have complex heart defects and extracardiac malformations, which can have direct implications in their treatment (especially the surgical one) and prognosis. 109536 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of Coronavirus Infection in Patients with Cardiovascular Diseases: A Systematic Review LUIS FILIPE RIBAS SOUSA1, Brenno Laerth Neves Sousa1, Gabriel Lino Ribas Sousa1, Rafaela Franca da Silva1, Yana Mara de Oliveira Coelho Mendes1, Elyanne dos Santos Gomes1, Marcus Vinicius Moreira Barbosa1 (1) Instituto Tocantinense Presidente Antonio Carlos de Porto Nacional - ITPAC Porto In December 2019, a city of China called Wuhan onset a new coronavirus infection, named Coronavirus Desease 19 (Covid-19), caused by Severe Acute Respiratory Syndrome-2 (SARS-CoV-2). It has affected more than 457 million people wordwide. The transmission occours person-to-person through contact to respiratory particles. Although SARS-CoV-2 is willing to cause respiratory sindromes, It may cause cardiovascular complications, even in those who do not have past medical history. Thereby, it is intended to do a systematic review, using the PRISMA methodology to identify cardiovascular outcomes in pacientes infected with Covid-19. Scielo and Pubmed are the bases used in this review. Free access articles published in English and Portuguese were included, according to the purpose of the study. It was analyzed 1.817 pacientes infected by Covid-19, where 62.5% male with mean age of 58,8 years-old. According to the database, cardiac manifestations of Covid-19 happened in those who had previous comorbidy, like essential hypertension, diabetes mellitus, dyslipidemia or smoking and alchol using. Miocardical injury are the most common complications, ranging from 8.1% to 36.6%. Arrhythimias were found in 12.7% to 17,6% and myocardical infaction in 0,4% to 9,9%. From this, the studies were able to asses point of care susceptible to cardiovascular complications in people with Covid-19. Among them, men aged over 60 years-old, who chronicle cardiac deasease and white blood cells (WBC) contage <=1,1 x 10^9 cells/L. It was pointed out that advanced age, especially in men, with risk factons, such as: smoking, diabetes mellitus, hypertension, dyslipdemia, chronic heart desease, chronic kidney desease with glomerular filtration rate <90l/day and WBC <=1,1 x 10^9 cells/L. It all worsens patient's prognosis. 109548 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Advanced Cardiac Life Support in Simulation for Undergraduate Students: There is Beneficial Data? LUCAS LUCENA BEZERRA1, Guilherme Aragao Melo1, Bruna Ferreira Apolinario Costa1, Maria Julia Pimentel de Albuquerque1, Cicero Samuel Tavares de Souza1, Lara Guedes Bezerra1, Mariana Diniz de Souza1, Natalia Lisboa de Carvalho Wanderley Cavalcanti1, Michelle Alves de Farias1, Antonia Raiane Silva Claudino1, Isabella Cristina Oliveira Pacheco1, Diego Felipe Ferrao Pereira de Andrade Barros1 (1) FACULDADE DE MEDICINA DE Introduction: In-hospital cardiac arrest (IHCA) is an emergency health issue that can lead to morbidity and mortality in a varied number of patients. In Brazil, there is not much data on IHCA found in the literature, but it is known that cases have a bad prognosis and low survival rates. For a better outcome for patients who need a good resuscitation at the IHCA, undergraduate students must go through adequate training to improve their knowledge in Advanced Cardiac Life Support (ACLS) when dealing with cardiac arrest. Objective: The main goal was to review and synthesize evidence on the following question: "What is the scientific evidence on the benefits of educational simulation interventions in advanced cardiology life support training in undergraduate students?". Methods: This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature research that was performed covered 3 databases (PUBMED, EBSCOHOST, AND ScienceDirect). The period of publication of the articles was from 2018 to 2022. Results: Among 350 articles retrieved, 9 papers were included and totalizes 1152 undergraduate students. Most studies used multiple-choice questionnaires to evaluate knowledge retention and cardiac arrest simulation or other skills tests to evaluate skills retention. The interventions, which were delivered in a variety of ways, have seen improvements such as: better patient outcomes, improved skills, and increased teamwork performance. In one of the articles, the pre-test score and post-test for ACLS knowledge had an 88% improvement. The performance of ACLS maneuvers that most follows the guidelines of the main world institutions, were in the high-fidelity simulation training scenarios. Conclusions: Simulation technology for resuscitation training as an innovative strategy for students, has brought great benefits to the ACLS learning process, helping bring better results in death prevention. However, more high-quality studies are needed, especially in Brazil. 109732 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Risk Behavior in Sexual Activity in Patients Submitted to Heart Transplantation GABRIEL SOUSA SANTOS1, Danielli Oliveira da Costa Lino2, Ane Karoline Medina Neri3, Carlos Jose Mota de Lima2, Glauber Gean de Vasconcelos2 (1) Universidade federal do Ceara, School of Medicine.; (2) Hospital de Messejana Dr. Carlos Alberto Studart Gomes.; (3) Universidade de Fortaleza, Postgraduate Program in Collective Health Heart transplantation is a surgical alternative used to treat heart failure unresponsive to clinical treatment, being responsible for improving the expectation and quality of life of patients who present such a condition. After a cardiovascular event, patients and their families deal with numerous changes, including the consequences of the disease or its treatment on everyday functioning. Individuals assume behaviors for which they are not prepared, such as initiating sexual intercourse early, often due to anxiety about living quickly and intensely. The onset of early sexual activity increases vulnerability to sexually transmitted diseases, which interferes with post-transplant survival. Sexual activity is an aspect of quality of life that is important to many patients and partners who may be adversely affected by a cardiac event. Although healthy sexual activity integrates quality of life, few studies addressing this theme have been developed in heart transplant patients. To assess risky behaviors in sexual activity in individuals undergoing heart transplantation. Descriptive research with a qualitative approach, with the interview of 30 heart transplant patients treated at the outpatient clinic specializing in Cardiac Transplantation in 2018. It was observed that 25 patients (83.3%) did not receive guidance on sexual activity. In 66.7% of respondents, risky behaviors were present, such as not using condoms reported by 50% of respondents, having multiple partners reported by 17.9% and early return to sexual activity, contrary to the recommendation of the cardiac transplant team, by 7.1% of the evaluated individuals. We evaluated the presence of risky sexual behaviors among individuals undergoing heart transplantation and observed that most participants had not received guidance regarding sexual activity in the post-transplant period and that most individuals practiced risky sexual behaviors. The contribution of the transplant team in the guidelines related to sexual activity is shown in a very timid way in the post-transplant guidelines, which may be contributing to a considerable prevalence of risky behaviors in these individuals. Supporting post-transplant providing guidance regarding sexual activity proves a coherent decision as a humanized practice. The deleterious clinical consequences of sexual risky behaviors, such as exposure to infections, can lead to cardiac impairment and reduced life expectancy in these patients. 109590 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Point-of-Care Ultrasound in Cardiopulmonary Arrest: A Systematic Review LUCAS LUCENA BEZERRA1, Mariana Diniz de Souza1, Guilherme Aragao Melo1, Cicero Samuel Tavares de Souza1, Maria Julia Pimentel de Albuquerque1, Bruna Ferreira Apolinario Costa1, Lara Guedes Bezerra1, Michelle Alves de Farias1, Natalia Lisboa de Carvalho Wanderley Cavalcanti1, Isabella Cristina Oliveira Pacheco1, Antonia Raiane Silva Claudino1, Diego Felipe Ferrao Pereira de Andrade Barros1 (1) FACULDADE DE MEDICINA DE Introduction: Despite significant improvements in cardiopulmonary resuscitation (CPR), sudden cardiac arrest is one of the leading causes of mortality. Nowadays, Ultrasound is a widely available tool that can be used to evaluate the presence of cardiac wall motion during cardiac arrest, which can be used to determine prognostic of the patient during CPR. We performed a systematic literature review of the existing evidence of point-of-care ultrasound (POCUS) in Cardiopulmonary arrest (CPA). Objectives: The main objective of this study was to systematically review and synthesize the published literature on the benefits of POCUS in CPA. Methods: The reporting of this study follows PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). The literature research that we performed covered 3 large databases (PUBMED, EBSCOHOST and ScienceDirect). The research was conducted gathering the articles from 2018-2022. We performed a systematic search in those databases up to 03/03/2022. Results: Initially, the literature search identified 120 articles, EBSCOHOST: 36; SCIENCEDIRECT: 15 and PubMed: 69. Furthermore, the updated withdrawal of duplicate articles was 74, leaving 22 articles selected. Finally, after the last selection, 6 articles were included in our review Among 15 papers, 9 were included and totalizes 356 patients. As for the articles included in our review, POCUS was used in order to identify the cause of CPA and the return of spontaneous circulation. When identified early, it increases patient survival. Thus, achieving greater diagnostic accuracy associated with less neurological and cardiac damage. Despite this, 2 of them suggest that POCUS should not be integrated into the protocols, so as to prolong pauses in CPR. They all also point out that POCUS depends on operator training and experience. Likewise, in one of the reports the instrumentator was trained in a four-hour training session, which included a didactic lecture and hands-on POCUS instruction. After this training, paramedics are prescribed to operate and enter the exam. Conclusions: POCUS has the potential to be an important tool in CPA and could potentially reduce health care costs. We conclude that POCUS is a powerful tool to assess reversible causes of cardiac arrest. However, it must be used in a protocolized and efficient way so as not to cause damage. 109592 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Assessing the Prevalence and Impact of Fake News About COVID-19 Vaccines and Heart Attack: A Youtube Study LUANA DE OLIVEIRA RIBAS1, Luana de Oliveira Ribas1, Silvia Nazare Braga Pereira1, Rebeca Bittencourt Jaqueira Rios1, Aline Goneli de Lacerda1, Claudio Tinoco Mesquita1 (1) Universidade Federal Introduction: In today's globalized world, the dissemination of Fake News in the medical field represents a great risk for the population's health. With the COVID-19 pandemic and the increasing of fake news circulation, including those of a general interest of medical nature, this phenomenon took on gigantic proportions, dominating social media. This scenario is propitious for the emergence of conspiratorial theories, pseudoscience and other misinformative speeches that represent a risk for public health. In this context, the purpose of this research is to survey and map the circulation of Fake News through videos in Portuguese that correlate COVID-19 vaccines and heart attack available on YouTube, popular and easily accessible data. Objective: Evaluate the veracity of Portuguese-language videos on the YouTube platform after a search relating the COVID-19 vaccine to heart attack. The initial objective was to evaluate the first 200 videos found. Methods: The data extraction was made through the YoutubeData Tools software through "Video Network", by the union of the key-words "vaccine" and "heart attack" utilizing the crawl depth 0 to identify the actors (videos) of most relevance about the subject. Then, the generated GDG file was imported to the software Gephi 0.9.2 responsible for the network analysis and visualization. Lastly, the 200 more relevant videos were analyzed for their content and labeled as truthful or containing Fake News. Results: 200 videos in Portuguese on the YouTube platform have been analyzed, obtained through the GDF file generated by the YoutubeData Tools. Of these, only 171 were classified as "True" or "Containing Fake News". Of the classified videos, 7 of them had fake news in their content, representing approximately 4.09% of the total videos analyzed. The authors of these videos almost always used persuasion strategies, such as the use of technical terms, doctoral degrees or the use of lab coats, as a way to convey a sense of trust. At the time of the survey, the total views of videos classified as "Containing Fake News" was 2,944,884. Conclusion: In the midst of the advancement of technology and disinformation detection tools, Fake News are still a reality in our daily lives and a threat to Public Health. Although most of the videos analyzed have a scientific basis, the existence of Fake News in the health sector can represent a serious danger to the general population, being therefore a topic of scientific and social relevance. 109594 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Hospitalizations for Phlebitis, Venous Thrombophlebitis and Venous Thrombosis in Brazil from 2017 to 2021 CAMILA SILVA DE OLIVEIRA1, Luiz Felipe Facanha Ramos1, Cecilia Rodrigues Viana1, Aurea Nathalia Gomes de Souza1, Bianca Paula Miranda Martins1, Vinicius Maciel Vilhena1, Larissa Silva Ferreira,1, Marcos Roberto Marques da Silva Junior1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa (UNIFAP) Introduction: Phlebitis presents as an inflammation of the intima of the veins, being caused by mechanical irritation, chemical or bacterial infection. Deep Vein Thrombosis (DVT), according to the Brazilian Society of Angiology and Vascular Surgery, is a disease caused by blood clotting inside the veins at an inappropriate place or time. And thrombophlebitis, according to the Brazilian Ministry of Health, consists of the inflammation of a clot formed when there is a thrombosis. In Brazil, data from the Ministry of Health put the three pathologies together and point out that women are the most affected due to risk factors such as pregnancy and use of contraceptives. Objective: To analyze the epidemiological profile for phlebitis, in all age groups, in Brazil, from 2017 to 2021. Method: Epidemiological study with a cross-sectional design of hospitalizations for phlebitis, venous thrombophlebitis and venous thrombosis in the regions of Brazil from 2017 and 2021. The investigated data were extracted from the SUS Hospital Morbidity System (SIM/SUS), from the database of the Department of Informatics of the Unified Health System (DATASUS). Results: In the investigated period, a total of 205,029 were documented. hospitalizations for phlebitis, venous thrombophlebitis and venous thrombosis. In 2017, the total was 40,238. The sum of hospitalization rates was higher in the Southeast region, which has about 55% of total hospitalizations in the period from 2017 to 2021, followed by the South region with 21.21%, the Northeast region with 15.93%, the Midwest and North region with7.74%. In the distribution of age groups, below 1 year to 19 years old are the least affected age with 1.61%, from 20 to 59 years old with 57.20% and 50 years or older with 40.85% of the total number of hospitalizations. It is worth mentioning that women are the most affected with about 154.34% more than men. When crossing the data with color/race, about 21.99% of the total hospitalizations were not identified, indigenous and yellow people with 1.97%, white people with 41.13% and black and brown people with 34% of cases registered. In total, 5292 deaths were recorded. Conclusion: Through the analyzed results, it was concluded that there was an increase in the rate of morbidity and mortality from phlebitis, venous thrombophlebitis and venous thrombosis in the period from 2017 to 2021. A higher prevalence was observed in white women aged 30 to 80 years. 109598 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY The Flavonoid Kamatakenin is a New Calcium Channel Blocker: Docking Molecular Analyzes CLARA DE ASSIS KAROLINE OLIVEIRA1, Clara de Assis Karoline Oliveira1, Adilson Lima dos Santos Junior1, Marcus Vinicius Guerra Canto1, Thacia Kiara Beserra de Oliveira2, Joelmir Lucena Veiga da Silva2 (1) de Medicina de Olinda; (2) DOCENTE - Faculdade de Medicina de Olinda Introduction: The cardiovascular diseases are evaluating due to risks and prevalence in world, as hypertension. The calcium-channel blockers (CCB) antihypertensives agents inhibit calcium-channel in the membrane of the vascular smooth muscle cells, it reduces calcium availability into cells impairing muscle contraction and decreasing vascular peripheral resistance. The flavonoid kumatakenin (5-hydroxy-2-(4-hydroxyphenyl)-3,7-dimethoxychromen-4-one), isolated from species vegetal Solanum paludosum, presented vasorelaxant effect in vitro by blocking the calcium channel (CaV). Thus, the researching by news drugs is a continuous process and natural products are a putative resource of medicines. Aim: To analyze the conformers and binding sites of kumatakenin on voltage-gated calcium channel by molecular docking. Methods: A quantitative and experimental research with an in silico approach that used the kumatakenin (CID 5318869) and nifedipine (CID 4485), standard drug, ligands from PubChem. To docking studies, atomics coordinates for the CaV, a structural basis of Ca2+ selectivity of a voltage-gated calcium channel, were retrieved from Protein Data Bank (ID 4MS2). The output conformers from Dockthor (GMMSB version 2.0), a receptor-ligand docking program, were ranked in order of increasing affinity with the protein. The affinity bonds (Ab) were obtained and compare using Test-t, where values p < 0.05 were significant. Results: There were three conformers that showed greater binding affinity with CaV and kumatakenin or nifedipine. The kumatakenin presented Ab of -8.353, -8.304 and -8.283, as the nifedipine of -8.021, -8.024 and -8.049. The comparing Ab into kumatakenin and nifedipine revealed significant difference (p < 0.05), showing that the flavonoid had more affinity than standard drug. The flavonoid conformer with the highest binding affinity occupies the most central region of the constriction, occupying a larger volume and justifying the events of greater amplitude of CaV blocker and greater reduction in the calcium conductance. The types of interaction involved in the connection between the three best docking solutions (flavonoid or nifedipine) and the CaV could be polar interactions, as salt bridge and carbon-hydrogen bond. Conclusion: The data confirm the blocking of voltage-gated calcium channel by kumatakenin in molecular insight, a putative CCB. It showed most affinity than nifedipine, a CCB antihypertensive. 109603 Modality: E-Poster Scientific Initiation - Non-case Report Category: PHYSIOTHERAPY Relationship between Waist Circumference and the Occurrence of Signs and Symptoms in Cardiac Rehabilitation Programs: An Observational Longitudinal Study ANNA JULIA LEAL RODRIGUES1, Heloisa Balotari Valente1, Lara Julia Montezori Costa1, Felipe Ribeiro1, Carolina Takahashi1, Lais Manata Vanzella1, Luiz Carlos Marques Vanderlei1 (1) Universidade Estadual Paulista "Julio de Mesquita Filho" (UNESP) Introduction: During cardiac rehabilitation programs (CRP) sessions patients may present signs and symptoms, which may be manifest prior to major adverse events, such as acute myocardial infarction and sudden cardiac death. Considering that high waist circumference is associated with a higher risk of major adverse events, it is important to investigate the relationship between waist circumference and the occurrence of signs and symptoms in CRP, since it may contribute to better conditions of cardiac risk stratification and to increased patient safety. Objectives: To investigate the relationship between waist circumference and the occurrence of signs and symptoms in CRP. Methods: 68 participants (65.81 +- 11.67 years) from an exercise-based CRP, diagnosed with cardiovascular disease and/or cardiovascular risk factors were included. Waist circumference was measured using a tape measure at the smallest point between the lower ribs and the iliac crest. The occurrence of signs and symptoms was assessed during 24 CRP sessions. The following signs and symptoms were assessed at the end of each step of the CRP session (initial rest, warm-up, resistance, and relaxation), and counted by session: arrhythmias, increased systolic (SBP) (>200 mmHg) and/or diastolic (DBP) (>120 mmHg) blood pressure during the exercise, tachypnea, pallor, angina, cramp, muscle pain, fatigue, dizziness, and nausea. Pearson's correlation or Spearman's correlation were used to evaluate the relationship between waist circumference and the occurrence of signs and symptoms, depending on the normality of the data (Shapiro-Wilk). The statistical significance level was set at <0.05. (CAAE: 79213417.0.0000.5402). Results: The average waist circumference found for the sample was 95.82 +- 9.72 centimeters (minimum: 70 centimeters; maximum: 119 centimeters). In total, 528 signs and symptoms were observed, which generated an average occurrence of 1 sign and symptom for each 3.09 hours of CRP session. No significant correlations were observed between waist circumference with total signs and symptoms (r = 0.111; p = 0.37), and with the main signs and symptoms observed in the 24 sessions: arrhythmias (r = 0.139; p = 0.26), muscle pain (r = 0.114; p = 0.35) and fatigue (r = -0.110; p = 0.37). Conclusion: Waist circumference is not related to the occurrence of signs and symptoms in CRP. 109610 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Analysis of Endovascular Repair of Abdominal Aortic Aneurysm in Brazil from 2016 to 2022 ISABELA ARAGAO COLARES1, Mariana Salles Ballalai1, Helena Raquel Nogueira de Oliveira1, Gabriel Sousa Santos1, Renata Pinheiro Martins de Melo1, Gabriel Coelho Brito Dias1, Jose Levi Tavares Cavalcante1, Ane Karoline Medina Neri2, Weiber Silva Xavier3, Joao Luiz de Alencar Araripe Falcao1, Sandra Nivea dos Reis Saraiva Falcao1 (1) Universidade Federal do Ceara, Faculdade de Medicina, Curso de Medicina; (2) Universidade Federal do Ceara, Faculdade de Medicina, Hospital Universitario Walter Cantidio; (3) Programa de Educacao em Reanimacao Cardiorrespiratoria Background: Abdominal Aortic Aneurysm (AAA) is a dilatation of that artery when its normal limit diameter of 2 cm is exceeded by 50%. It is considered a lethal event because of its risk of rupture, therefore Endovascular Aneurysm Repair (EVAR) is considered to be an important treatment for this condition, as it is indicated in the treatment of ruptured aneurysms and in elective endovascular procedure, if anatomically viable, according to the August 2016 recommendations of Brazilian Guideline for the treatment of AAA. Objectives: Observe the aspect of health care in the performance of EVAR, as well as in each Brazilian geographic region by verifying the data on hospitalizations, average hospital stay, mortality rate and death toll. Methods: The data available at DATASUS platform, provided by the Hospital Information System (SIH), from August 2016 to January 2022, were quantitatively and descriptively analyzed. Results: The EVAR with straight or conical endoprosthesis, of this period, performed electively, represents 135 hospitalizations, with a mean stay of 9.9 days, with a mortality rate of 5.10 and 7 deaths. As for the urgent care, there were 303 hospitalizations, with an average length of stay of 8.5 days, a mortality rate of 9.9, and 30 deaths. Furthermore, it was possible to verify the following information about each geographical region: the South had the highest number of hospitalizations, with 202 patients, and a mortality rate of 13.52, while the North had the lowest number of hospitalizations, 10 in total, and the second highest mortality rate, 14.82. Still, the Midwest Region showed the highest mortality rate, 15.12, among the 20 hospitalized patients. The Southeast presented 167 hospitalizations for the procedure in question, with a mortality rate of 13.02. The Northeast, with 42 hospitalizations, had a mortality rate of 13.03. Conclusion: EVAR is recommended for reducing early morbidity and mortality and is a technique that can be increasingly improved, as well as the care after the procedure. Moreover, it has a significant mortality rate in emergency treatment compared to elective due to the patient's clinical condition, which is directly related to the anatomical evaluation and success of EVAR. Additionally, the differences in mortality rates in each Brazilian region may be related to the character of the care, the clinical status and recovery of the patient, as well as the existence of local reference services. 109635 Modality: E-Poster Scientific Initiation - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Association between Spirituality and Depression Among Hypertensive Outpatients VITHORIA VIDOTTI NEVES1, Julio Cesar Tolentino Junior1, Victor Pacheco Zanela Monte1 (1) Hospital Universitario Gaffree e Guinle Introduction: Depression is associated with greater morbidity and mortality in hypertensive patients. Then, it is important to know potential protective factors for depression in these individuals. Studies have demonstrated that spirituality protects against depression in the general population. Therefore, we hypothesized that spirituality would be a predictor of depression. Additionally, higher spirituality could be related to less depression severity in this population. Objectives: 1) Investigate spirituality as a predictor of depression among hypertensive patients; 2) Analyze the association between spirituality and depression severity. Method: This cross-section study was carried out in hypertensive outpatients at a University Hospital. Depression was diagnosed by DSM-5 criteria. The Patient Health Questionnaire-9 evaluated depression severity. Spirituality was assessed through the Functional Assessment of Chronic Illness Therapy -Spiritual Well-Being (FACIT-Sp). In this widely validated questionnaire, total scores range from 0 to 48, with higher scores indicating higher spiritual well-being (SWB). With SPSS 25(r), continuous variables were analyzed using the t-test and linear regression. The binary logistic regression model was performed to predict depression using sex, age, religious affiliation, and FACIT-Sp score as predictors. Data were presented with their respective 95% confidence intervals (95%CI) and odds ratios (OR), considering a significance level of 5%. Results: We included 150 hypertensive outpatients. The age ranged from 28 to 80 years (53.5 +- 14.9), and 69.3% were female. The prevalence of depression was 29.3%. The mean FACIT-Sp score was significantly lower in depressive patients than those without depression (39.5 and 30.2, respectively; p < 0.001). The logistic regression model was statistically significant [kh2(2) = 34.0, p < 0.001] and the Wald test indicated that female sex (OR = 3.884; 95%CI: 1.231-12.253; p = 0.02) and FACIT-Sp score (OR = 0.882; 95%CI: 0.836-0.930; p < 0.001) added significantly to the model. Then, SWB was the strongest depression predictor. The FACIT-Sp has a significant negative association with the PHQ-9 (F(1,148) = 52.205; p < 0.001; R = 0.51; R2 = 0.261). Conclusion: Spirituality was considered a protective factor for depression in hypertension outpatients. In addition, the higher SWB was associated with lower depression severity. These results highlight the importance of spirituality in the approach of hypertensive patients. 109638 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiology of Hospitalization and Costs of Heart Failure Treatment in the Northern Region of Brazil from 2017 to 2021 LUIZ FELIPE FACANHA RAMOS1, Karen Tassia Facanha Ramos1, Hildeman Dias da Costa2, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia Introduction: Heart failure (HF) is characterized by complex syndromes that compromise tissue metabolic demands. There are about two million new diagnosed cases of HF per year in the world, constituting the leading cause of hospital admission in the elderly in Brazil. In this sense, it impacts on the increase in the costs of treating patients, thus being an important public health problem. Objective: To trace the epidemiology and treatment costs of HF from 2017 to 2021 in the northern region of Brazil. Methodology: This is an analytical ecological study of time series and geographical distribution about hospitalization cases and HF treatment costs in the northern region of the country, using secondary data by place of residence (from 2017-2021) from the Department of Informatics of the Unified Health System (DATASUS), through the Hospital Information System and the Hospital Morbidity System, for the evaluation of frequencies, case rates and association factors. Results: In the period 2017-2021, there were 52,963 hospitalizations for HF treatment in the North region of Brazil, which represented a cost of BRL 78,913,522.84 (with an average cost of BRL 1,489.97 per hospitalization) and with a growing trend in average spending on these services (1,658.32 in 2021). There was a drop in these hospitalizations in the period, and the State of Para and Amapa, respectively, had the highest (42.14%) and lowest (2.2%) percentages of hospitalizations. In the region, there was an average length of stay of 8.2 days of hospitalization (ranged from 8.1 to 8.4 days) and a mortality rate of 11.97% (n = 6,319), with the year 2019 had the highest number of deaths (n = 1,415). The state of Roraima had the highest mortality rate from HF treatment (16.09%). It is noteworthy that associated factors that were more expressive are people of mixed race (n = 31,456), aged between 70 and 79 years (n = 12,608) and males (n = 29,921). Conclusions: During the study period, HF had a high number of hospitalizations in the northern region of the country, with an increase in average treatment costs over the years, with the highest average cost in 2021, although the number of hospitalizations has decreased. It is worth noting the State of Para with the highest number of hospitalizations and the State of Roraima with the highest mortality rate due to HF, and 2019 was the most lethal year for HF. Finally, it was noticed that HF affects more brown men aged 70 to 79 years. 109642 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Presence of the Third Heart Sound as a Predictor of Mortality in Patients with Heart Failure in a Referral Hospital in the North of Ceara FELIPE SALIM HABIB BUHAMARA ALVES NASSER GURJAO1, Felipe Salim Habib Buhamara Alves Nasser Gurjao1, Mateus de Sousa Cavalcante1, Bruna de Almeida Freixedelo1, Dara Medeiros Mendes1, Benedito Mesley Lima Portela1, Joao Marcos de Fontes Carneiro1, Daniel Salmito Chaves1, Paulo Roberto Matos Neto1, Luis Eduardo Rodrigues Reis1, Leandro Cordeiro Portela1 (1) Universidade Federal do Ceara - Campus Sobral Introduction: The third heart sound (S3) corresponds to a protodiastolic gallop, which results from the ventricular resistance to the rapid filling phase of diastole. In heart failure, S3 is a marker that indicates systolic dysfunction. Thus, the presence of S3 may be an important feature in the diagnosis and prognosis of patients with heart failure. Means: In this study, the objective is to analyze the relevance of the presence of S3 during hospital admission as a marker of mortality in patients at Hospital do Coracao in Sobral with heart failure. Methodology: This is a prospective cohort study obtained with primary data, using as a sample patients admitted to the Hospital do Coracao de Sobral with heart failure between the years 2015 to 2019. Thus, at moment of hospital admission the patients who participated in the study had auscultation performed, in order to determine the presence or absence of S3. Then the data was correlated with the in-hospital mortality of these patients. The informations were submitted to statistical analysis using the Chi-Square test, using the OpenEpi program, with a significance value of p = 0.0001. Results and discussion: This study obtained relevant data from 314 patients during this period. From those pacientes, only 21 (6.68%) had S3 at the time of hospital admission, from which 7 (2.23%) died. On the other hand, from the other 293 (93.31%) patients who were denied the presence of S3 at hospital admission, only 16 (5.09%) died. Thus, the risk of death in patients who were admitted with the presence of S3 in auscultation was 33.33%, while the risk of patients who were not admitted with S3 was 5.42%. Therefore, patients admitted with the presence of S3 on auscultation are 6.1 times more likely to die than patients without the presence of S3 during hospital admission. Conclusion: Based on the data analyzed, it can be seen that the presence of S3 during hospital admission of patients with heart failure may be an important marker of in-hospital mortality. Thus, larger studies on the subject are necessary. 109647 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Number of Deaths from Acute Rheumatic Fever between the Years 2010 to 2019 ORLANDO SEIXAS ROCHA NETO2, Orlando Rocha Seixas neto2, Ellen Magnavita Seixas Santos2, Luiz Augusto Ferreira Alvarez2, Katarina Pereira do Lago2, Cinayra Daisy Fraga de Souza2, Ingrid Porto Gomes2, Beatriz Souza Bastos2, Ian Felipe Mariano Goncalves2, Leticia Barbosa Machado de Lima2, Mauricio Santa Fe Lins Junior2, Bruno Cunha Freitas2 (1) Universidade Salvador; (2) Liga Baiana de Cirurgia Cardiovascular Introduction: Rheumatic fever (RF) is an inflammatory, systemic disease triggered after an infection in pharyngotonsillitis and its etiology is group A beta-hemolytic streptococcus (ECGA). Early attention to pharyngitis coupled with antibiotic use can greatly reduce the risk of RF and its complications. In view of this scenario, one of the factors that may have implied a significant increase in this pathology in the national territory during the period 2010-2019 is the shortage of the main antimicrobial used in prophylaxis: benzathine penicillin. Objective: To assess the number of deaths from acute rheumatic fever in Brazil from 2010 to 2019 and to correlate the shortage of the main antibiotic used for the disease, benzathine penicillin, and poor adherence to treatment. Methods: A cross-sectional observational study of aggregated data, collected through the collection of information through the SUS Hospital Information System (SIH-SUS) by the SUS Department of Informatics (DATASUS), where the number of deaths in years from 2010 to 2019 related to acute rheumatic fever by macroregions of Brazil. The Kolmogorov-Smirnov test was performed for the subsequent adequacy of the tests of comparison of parametric or non-parametric groups. A linear regression in the 10 years surveyed was also performed to assess the increase in deaths in the Brazilian territory in this period. Results: In the linear regression from 2010 to 2019, throughout Brazil, there was evidence for an increase in deaths related to acute rheumatic fever, with the following results: b = -0.848; R2 = 0.719; p = 0.002. Conclusion: Finally, it was possible to observe that, with regard to the mortality rate, the studies showed that in the period in which there was a shortage, the numbers of deaths increased, demonstrating a failure to adhere to treatment or a low continuity. of Streptococcus pyogenes prophylaxis in patients. However, even based on this assumption, the adoption of an adequate clinical approach for continuity in prophylaxis in order to avoid cardiac impairment and access to health resources for treatment is the most recommended, in order to modify these statistics. 110035 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Golden Ratio Deviation, SBP/DBP and DBP/PP Coefficients in Normotensive, Pre-Hypertensive, Hypertensive and Diabetic Patients - Clinical Applicability LOUISE BUONALUMI TACITO YUGAR1, Tatiana Rubio Azevedo2, Larissa Costa Morete2, Beatriz Vaz Domingues Moreno1, Bruno Rodrigues1, Jose Fernando Vilela Martin2, Heitor Moreno Junior1, Lucia Helena Bonalume Tacito2, Juan Carlos Yugar Toledo2 (1) Faculdade de Ciencias Medicas, UNICAMP; (2) Faculdade de Medicina de Sao Jose do Rio Preto, FAMERP Introduction: The golden ratio (ph, phi) is defined as a line divided into two parts of different size (a and b, in which a > b) so that the ratio of the whole length to the larger one is equal to the ratio of the larger number to the smaller. It is approximately 1,61. This number is found throughout the body as in fingers, uterus and the cardiovascular system. The blood pressure curve can be segmented in three parts: pulse pressure (PP), diastolic blood pressure (DBP) and systolic blood pressure (SBP), which is the sum of DBP and PP. In this paper, we aimed to analyze geometrically these values in the form of proportions (DBP/PP and SBP/DBP) to assess if the deviations from phi can be used as additional markers of cardiovascular risk. Material and methods: This retrospective study analyzed data of 171 normotensive patients (NT), 78 pre-hypertensive patients (PHTN), 46 hypertensive people (HTN) and 81 diabetic people (T2DM) from the study "Vascular hemodynamic alterations in HTN and T2DM type 2 patients". The protocol was approved by the local ethical committee. We used age, sex, SBP, DBP, PP and pulse wave velocity (PWV) for the analysis. We made a descriptive statistical analysis along with t test and ANOVA in SPSS 24 (USA). Results: We observed lower SBP/DBP in PHTN and HTN when compared to NT (p = 0,0002 e p < 0,0001, respectively). Between PHTN and HTN, PHTN and T2DM, there was a significant difference. The DBP/PP ratio showed greater values in PHTN and HTN when compared to HTN (p < 0,0001 in both) and lower and we compared T2DM and NT (p = 0,0495). The comparison between PHTN and HTN, PHTN and T2DM, as well as HTN and T2DM showed significant difference. Multivariate regression in the different groups demonstrated that age and PWV are correlated to SBP/DBP in HTN and there's a correlation with sex, age and PWV in T2DM. Additionally, we found significant correlation between SBP/DBP and DBP/PP with PWV and PP in the four groups. Conclusion: Deviations from phi were detected in PHTN, HTN and T2DM with different pattern among the groups and can be used as additional risk evaluators as well as markers of cardiovascular damage and are closely related to vascular accelerated ageing for its relation with PP and PWV. 109660 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Changes in the Epidemiological Profile of Cardiovascular Mortality in the Face of the COVID-19 Pandemic Scenario: A Focus on the Brazilian Reality GABRIELA CUNHA FERNANDES2, Sylton Arruda de Melo1, Juliana Maria Gurgel Guimaraes de Oliveira1, Ana Isabelly De Medeiros Tomaz1, Arthur Felipe Tertulino Cunha1, Pedro Nonato Silveira Costa1, Mateus Bessa Nogueira2, Sara Araujo de Oliveira Lima2, Maria Teresa da Fonseca Madruga2, Maria Laura Torres e Araujo2, Joice Raquel Urbano Nascimento2, Flavia Diogenes Forte Melo2 (1) Universidade Potiguar - UnP; (2) Liga Academica de Cardiologia do Rio Grande do Norte (LiCordis-RN) Introduction: In view of the pandemic caused by SARS-Cov 2, a broad approach to the disease and its repercussions is extremely important. Unquestionably, COVID-19 has potentially serious outcomes: cardiovascular, pulmonary, systemic repercussions and death, but we must also consider its impact on the health system in general. Objective: To analyze the mortality rate from cardiovascular diseases (CVD) before and during the pandemic, noting the epidemiological situation in Brazil. Methods: Cross-sectional, retrospective and portal study, through the analysis of transparency data - civil registry. It was a survey on the number of deaths from CVD in Brazil, considering the pre-pandemic period of the year 2019 (from January), and the pandemic scenario of 2020, 2021 until March 15, 2022. Results: The period from January 2019 to March 15, 2022: in 2019 there were 275,032 deaths from cardiovascular causes, of which 37.2% (102,361) were due to stroke, while 36.4% (100,378) were due to acute myocardial infarction (AMI) and 26.2% (72,293) due to unspecific cardiovascular causes. In 2020, 293,963 deaths were observed, with 35.1% (103,238) from stroke, 32.6% (96,023) from AMI and 32.2% (94,702) from unspecific cardiovascular causes. In 2021, there were 318,602 deaths, 33.5% (106,817) from stroke, 32% (102,098) from infarction and 34.4% (109,687) from unspecific cardiovascular causes. In the year 2022, until March, 62,310 deaths were recorded, with 34.5% (21,522) deaths from stroke, 31.8% (19,831) from AMI and 33.6% (20,957) from unspecific cardiovascular causes. Conclusion: An increase in the number of deaths from cardiovascular causes was observed between 2019 and 2022, with a significant increase in the number of deaths from nonspecific cardiovascular diseases (26.2% to 33.6%). However, in 2022, until the analyzed period, a predominance of mortality from stroke was evidenced and that nonspecific cardiovascular causes remained close to the percentage numbers between 2020 and 2021, still above the observed in 2019. It's concluded that there was an increase in deaths from CVD in a pandemic scenario in Brazil, which can be attributed to the fear of patients to seek medical care in the face of the risk of contamination, reaching more advanced stages or even dying outside the hospital environment. In addition, the increase in the number of deaths from unspecific cardiovascular causes can be largely attributed to mortality from the cardiovascular repercussions of COVID-19. 109663 Modality: E-Poster Scientific Initiation - Non-case Report Category: NURSING Nursing Diagnoses and Cardiovascular Risk Factors Related to Oral Health in Homeless Women in Sao Paulo City, Brazil AMANDA CIRILO SILVA1, Andreia Correia de Menezes1, Ingrid Milani Nacaratto de Freitas1, Claudia Cristina Soares Muniz1, Everaldo Muniz Oliveira1, Fernanda de Mello Demai1 (1) Universidade Nove de Julho Introduction: The homeless population in Brazil is minority composed of women, which represent only 14.6% in the city of Sao Paulo1, where they are commonly affected by the scarcity in which they live, without health information and lack of access to personal and oral hygiene. We used the nursing diagnoses and possible interventions aiming to produce quality of life and reduction of damage to their health. Objective: To evaluate cardiovascular risks to oral health in homeless women in Sao Paulo, associated with the Taxonomy of International Nursing Diagnoses Nanda I 2018/2019. Methods: This is a field research with quantitative method, exploratory and cross-sectional nature, approved by the Institutional Ethics Committee under protocol 036417, CAAE:21519413.40000.5511. Conducted in downtown Sao Paulo, the research counted among 173 evaluated, it was found 18 women volunteers in street situation between the months of November 2019 to March 2020, having between 18 and 59 years, previously selected by convenience and submitted to a questionnaire, being evaluated sociodemographic data pointing the risk factors for cardiovascular diseases (CVD), measurement of blood pressure (BP) and heart rate (HR), subsequently associated with the International Nursing Taxonomy Nanda I. Results: Of the women studied the mean blood pressure (BP) of 128 x 85 mmhg, and Heart Rate (HR) of 91bpm. Being that 18.1% reported having previous history for stroke, 9% for AMI and 76.6% could not inform previous history for AMI. Of these women, 18.1% reported having presented an abscess or edema in the last 6 months. And 27.2% reported toothache or pain in the mucosa region. It was observed that 72.70% of the women answered that yes, they use some illicit substance, 18.1% never used and 9% do not use. Thus, nursing diagnoses were listed during the analysis, using the NANDA I taxonomy, are: Related Ineffective Health Control, Impaired Dentition, and Risk of Impaired Oral Mucous Membrane Integrity. Conclusion: However, it is evidenced that oral hygiene has a direct connection with cardiovascular alterations in this population associated with AMI, stroke, and atherosclerosis. Thus, the importance of public politics for the improvement and eradication of this problem was observed, reducing the aggravations of CVD and aiming to improve the quality of life for this often underprivileged part of society. 109752 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Evolution of Mortality from Cardiomyopathies in Brazil LUIZ FELIPE FACANHA RAMOS1, Karen Tassia Facanha Ramos1, Hildeman Dias da Costa2, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Leo Christyan Alves de Lima3, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia; (3) Centro Universitario Sao Lucas Introduction: Cardiovascular diseases are an important cause of mortality in the country, representing the main cause of mortality from all causes, especially cardiomyopathies. Objective: To analyze the evolution and profile of mortality from cardiomyopathies in Brazil in 3 consecutive years. Methods: This is an epidemiological, cross-sectional study on mortality from cardiomyopathies (ICD I42) from 2017 to 2019, in Brazil, using secondary data from the Department of Informatics of the Unified Health System (DATASUS). Results: In the analyzed period, there was a 2% increase in mortality from cardiomyopathies, from 2017 to 2019, totaling 23,061 deaths, with the year 2018 having the highest mortality in the period (n = 7,834). During this period, the southern region of the country had the highest number of deaths (n = 14,658) and the northern region had the lowest number (n = 651). Analyzing the age group, marital status, sex and color, there were more deaths, respectively, among people aged 60 to 69 years (n = 7,412), single (n = 8,683), male (n = 15,904) and white people. (n = 10,387). Conclusion: Thus, there was an increase in the number of deaths during the period studied, especially in 2018. In addition, there were more deaths in the south of the country, in the elderly, single and white. Therefore, there is an urgent need for public health policies for the southern region of the country to contain the advance of mortality from cardiomyopathies. 109687 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Indirect Effect of the COVID-19 Pandemic on Mortality from Arterial Embolia and Thrombosis in Brazil LUIZ FELIPE FACANHA RAMOS1, Karen Tassia Facanha Ramos1, Hildeman Dias da Costa2, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia Introduction: The disease caused by the SARS-CoV-2 virus (COVID-19) has been responsible for high rates of hospitalization and high mortality. In addition to respiratory failure, coagulopathy has become a recurrent complication in infected patients, especially the most severe, thus increasing the number of arterial embolisms and thrombosis in the country. Objective: To analyze the effect of the COVID-19 pandemic on cases of arterial embolism and thrombosis in Brazil. Methodology: This is an ecological time series analytical study, using secondary data on arterial embolism and thrombosis (from 2017-2021) in the country based on the Department of Informatics of the Unified Health System (DATASUS), through the Information System of the Unified Health System (DATASUS). Hospital Morbidity. The data were tabulated in two spreadsheets - period 1 (P1): data from 2018-2019; period 2 (P2): 2020-2021 - of the Microsoft Excel software, which were analyzed by the GraphPad Prism software version 9, using the test of Wilcoxon and Pearson's chi-square test to assess differences in rates, association factors, risk ratio (RiR) and their 95% CI, with a significance level of 5%. Results: Analyzing the two groups of data, there was an increase in mortality from arterial embolism and thrombosis in Brazil during the pandemic period (from n = 3736 to n = 4215; p = 0.05; RiR 1.00; 95% CI 0.99-1.00), also expressed by the difference in standardized mortality rates, since P2 had a higher rate than P1 (8.76 and 8.37, respectively; p = 0.18). It should be noted that the number of deaths was higher in the elderly in both periods (P1, n = 3125; P2, n = 3474), with P2 being the most lethal for people aged 60 years or older (p = 0.14; RiR 0, 95; 95% CI 0.89-1.01). It is noteworthy that the number of deaths occurred more in females in both temporal groups (p = 0.07; RiR: 0.95; 95% CI 0.91-1.00) and in white people (p < 0.0001; RiR: 0.89; 95% CI 0.85-0.93). Conclusions: During the pandemic, the indirect effect was the increase in the number of deaths and mortality rates from arterial embolism and thrombosis in the country, when compared to the same period 2 years before the beginning of the pandemic period. In addition, in the two analyzed periods, deaths occurred more among women, elderly people aged 60 years or older and white people. Thus, we can see the importance of investing in surveillance and effective treatment of this morbidity to possibly reduce the number of deaths. 110173 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Analysis of the Number of Healthy Metrics in Women with Chronic Ischemic Heart Disease According to Current Therapeutic Recommendations MARIA EDUARDA BERGAMO1, Maria Eduarda Bergamo1, Gustavo Henrique Ferreira Goncalinho1, Nathalia Ferreira de Oliveira Faria1, Karen Lika Kuwabara1, Jose Rafael de Oliveira Nascimento1, Gean dos Santos de Sales1, Antonio de Padua Mansur1 (1) Insituto do Coracao - HC FMUSP Introduction: Ischemic heart disease (IHD) is the leading cause of death in women. Despite advances in the treatment of IHD, little is known about how this knowledge is applied in current outpatient clinical practice. This study aimed to analyze the number of healthy metrics (HM) the clinical response to the recommended treatment in women with IHD. Methods: This cross-sectional study analyzed 462 women with IHD in outpatient care aged >=30 years. IHD was diagnosed by cardiac catheterization for coronary lesions >70%. The response to clinical treatment was analyzed by quantifying the number of HM, namely: healthy eating (DASH-Dietary Approaches to Stop Hypertension diet), physical activity (PA), body mass index (BMI = 18.5-24.9 Kg/m2), blood pressure (SBP <=140 and DBP <=90 mmHg), non-smokers, LDL-cholesterol <=50 mg/dL, glucose <126 mg/dl. Results: Mean age was 66.5 years; 340 (74%) women with chronic IHD had 3 and 4 HM outside the targets established by current guidelines; 47 (10%) had none or one HM; only 0.4% (n = 3) with all HM. Only 17 (3.7%) of the patients practiced physical activity (PA) regularly, and the entire study population did not have a healthy eating pattern assessed by the DASH diet. The table shows the prevalence of HM analyzed and the mean values of clinical and metabolic variables. Conclusion: The quality of outpatient care for women with chronic IHD did not meet the strategies recommended by current guidelines. 109693 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cardiovascular Continuum - is There Room for Analysis of Arterial Stiffness in the Assessment of Heart Failure with Reduced Ejection Fraction? MARIA GABRIELA PIMENTA DOS SANTOS1, David Ferreira de Lima Duarte1, Gabriela Gama Zagni Jardim2, Julia Resende de Oliveira1, Antonio Carlos Eberienos Assad Filho1, Paola Pugian Jardim3, Andrea Vaospasse Cocco Faria3, Lilian Soares da Costa4 (1) Universidade Estacio de Sa/IDOMED, Campus Citta; (2) Universidade Estacio de Sa/IDOMED, Campus Vista Carioca; (3) Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (4) Universidade Estacio de Sa/IDOMED, Campus Citta e Vista Carioca; Instituto Estadual de Cardiologia Aloysio de Castro/IECAC Introduction: Arterial stiffness measured by pulse wave velocity (PWV) is considered the gold standard in different national and international guidelines, being a parameter of significant prognostic value of cardiovascular (CV) risk. Although the assertion that elevation of PWV increases the occurrence of CV events, CV mortality and death from all causes, its prognostic value in very high-risk individuals, such as heart failure with reduced ejection fraction (HFrEF), is not yet well established. Objective: Evaluate the oscillometric analysis of vascular pulsatile hemodynamics, using PWV, in patients with HFrEF. Materials and Methods: A cohort study evaluating patients with HFrEF, followed up at a tertiary cardiology hospital in the State of Rio de Janeiro. Blood pressure measurements, PWV, anthropometric measurements and chart analysis were performed. Results: PWV was analyzed in a series of sixteen consecutive cases of individuals with compensated HF and severe systolic dysfunction, comprising a cohort of 180 individuals at high CV risk, which 56% was male and mean age was 64.6 years (36-87 years). The subgroup is composed of sixteen patients, 75% male, mean age 63.4 years (44-78 years), HFrEF with mean EF 30.3% (18-40%). We emphasize that twelve individuals had three or more major risk factors or comorbidities, such as diabetes mellitus, arterial hypertension, dyslipidemia and coronary artery disease. A risk score for arterial stiffness (SAGE Score) was applied on the study population and demonstrated values within normal limits in 14/16 individuals. Blood pressure values within normal parameters were found in 5/16 participants and, in 2/16, arterial stiffness parameters were recorded above the median standards considered normal for the Brazilian population, adjusted for age, sex and presence of factors of risk. Conclusion: As assumed in the literature, a greater number of individuals is needed to confirm the role of this tool as a CV prognostic marker in this particular group of very high-risk individuals with HFrEF. The future perspective of our cohort is that the possibility of pharmacological interventions in the short and medium term can modify these parameters, in order to assess outcomes, for possible assessments of inferences about the role of PWV in CV prognosis. 109700 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Gastrointestinal Tract Malformations Among Patients with Congenital Heart Disease GUILHERME RODRIGUES VIANA1, Grasiele do Amaral Martins1, Marco Antonio Vinciprova Dall Agnese1, Adriano Louro Moreira1, Pedro Henrique Torres Tietz1, Bianca Brinques da Silva2, Caroline Engster da Silva1, Eric Seiji Kanai1, Estefany Karenine Rodriguez Casanova1, Leticia Vieira Senger1, Matheus Ribeiro Fretes1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre; (2) Universidade Luterana do Brasil Introduction: Extracardiac malformations (ECMs) associated with congenital heart disease (CHD) may increase the risk of morbidity and mortality of the child, often making surgical intervention risky. This association between ECMs and CHD may involve defects of different systems or tracts, such as the gastrointestinal tract (GIT). Purpose: To determine the frequency and types of GIT malformation in a sample of patients with CC. Methods: A retrospective study using Clinical Data from patients hospitalized for the first time in a cardiac intensive care unit of a reference pediatric hospital in southern Brazil. In the present study, ECMs and CHD data were obtained by filling out a standard protocol. Results: The sample was composed of 343 patients, 182 (53.1%) males, ages ranging from 1 day to 14 years and 6 months (60.1% <1 year). GIT changes were evident in 6 patients (1.7%) and consisted of esophageal atresia (n = 2), duodenal stenosis (n = 1), multiseptated gallbladder (n = 1), anteriorized anal canal (n = 1), and imperforate anus (n = 1). The most commonly observed CC among patients with GIT malformations were septal defects (n = 3), in particular ventricular septal defect (n = 2). Four patients were syndromic, and chromosomal alterations were observed in 5 patients. Conclusion: From the information of the presence of an associated GIT alteration, health professionals can perform a more detailed and directed evaluation of patients with CC, aiming at the best management of these patients and preventing future complications, mainly related to their prognosis. 109714 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality from Circulation Diseases and the Evolution of Family Health in Brazil: An Ecological Study LUIZ FELIPE FACANHA RAMOS1, Karen Tassia Facanha Ramos1, Hildeman Dias da Costa2, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa; (2) Universidade Federal de Rondonia Introduction: The Family Health Strategy (FHS) stands out, among many factors, for its comprehensive care for people living with non-infectious chronic diseases, especially circulatory diseases, which represent the main cause of death and physical disability in the world. However, there are few studies that associate the advancement of the FHS to the parameters of these diseases, making systematic evaluations of its expansion necessary. Objectives: The objective of this study was to analyze mortality from circulatory diseases in parallel with the evolution of the FHS from 2017 to 2020 in Brazil. Methods: This is an ecological, retrospective study, based on the temporal evolution of the FHS, inhabitant coverage x FHS, and on standardized rates (per 10,000 inhabitants) of mortality from circulatory diseases in Brazil. Secondary data were taken from the SUS Hospital Morbidity System, from the Information Technology Department of the Unified Health System (DATASUS), and from the Primary Care Information and Management System, using the Spearman Correlation test, through the GraphPad Prism software version 9.3.1, for statistical association. Results: During the analyzed period, there was a 2% population increase in Brazil, a 4.7% increase in the number of FHS and a 20.5% increase in mortality from circulatory diseases. The population x FHS ratio increased from 4,965 (2017) to 4,834 (2020) people assisted (2.6% higher coverage). In 2020, the northeast region had the best population coverage by FHS, reaching 3,520 people per implemented unit. Even with the expansion of the FHS in the country, mortality from circulatory diseases increased in all regions, with the northern region having the highest increase (34%). When analyzing the data from the regions, it was noticed that in three there was a positive correlation between FHS and mortality from circulatory diseases (r > 0.7; p < 0.05) and the south and southeast did not present a significant correlation (r: 0, 2; p = 0.91). Overall, Brazil showed a positive correlation between FHS and mortality from circulatory diseases (r: 0.8; p = 0.33). Conclusion: Thus, this study demonstrated that, even with the increase in population coverage by the FHS in Brazil, there was no reduction in mortality from circulatory diseases and that they are a challenge for public health policies. In addition, there was a large increase in mortality from 2017 to 2021 that did not follow the growth of FHS coverage in the same proportion. 109745 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Analysis of the Clinical Profile and Outcomes of Patients with Previous Cardiovascular Disease and COVID-19 CAMILA THAYNA DE MENEZES CLEMENTE1, Mariane Leandro Ferro de Sousa1, Matheus Dantas Soeiro1, Carolina Jeronimo Magalhaes3, Jessica Myrian de Amorim Garcia1 (1) Faculdade Pernambucana de Saude; (2) Real Hospital Portugues de Beneficencia em Pernambuco; (3) Universidade de Pernambuco Introduction: Cardiovascular diseases (CV) is the most prevalent chronic conditions worldwide. The coronavirus disease 2019 (COVID-19) infection leads to heterogeneous clinical manifestations throughout the population. Therefore, it was necessary to establish the interplay between cardiovascular disease and COVID-19. Objective: Analyze the clinical profile and outcome of patients with and previous CV disease compared with patients with COVID-19 without these comorbidities. Methods: A cross-sectional observational study of inpatients presenting with COVID-19. Conducted in a private Brazilian hospital from August 2020 and August 2021. The diagnostic criteria were a positive reverse transcriptase-polymerase chain reaction (RT-PCR) or ground-glass opacities on computerized chest tomography with compatible clinical manifestations of dyspnea, fever, and cough. The data were obtained from online medical records. Results: We studied 212 patients with COVID-19. The sample had a mean age of 58.4 years, and 55.7% were males. There was a 50.5% prevalence of previous CV disease, 98.1% of these group of patients had systemic arterial hypertension, 11.2% acute myocardial infarction, and 13.0% congestive heart failure. The patients with both COVID-19 and CV disease were associated with greater mean inflammatory markers D-Dimer (p = 0.03) and troponin (p < 0.01) (TABLE 1). Patients with COVID-19 and CV disease had a greater incidence of shock (p = 0.01), anemia (p < 0.01), bacteremia (p = 0.03), and worse outcomes marked by an extended hospital stay (p = 0.04) as well as 80% of the deaths (TABLE 2). Conclusion: Patients with previous cardiovascular disease infected by COVID-19 had a poorer prognosis and were subject to worse clinical course and complications during of hospitalization. 109755 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Incidence of Acute Myocardial Infarction in Young Population DANIEL DE OLIVEIRA MEIRELES 1, Sara Cristine Marques dos Santos1, Aline de Jesus Oliveira1, Thais Lemos de Souza Macedo1, Ivan Lucas Picone Borges dos Anjos1, Julia Bardela de Oliveira1, Anderlucia Correa Guedes1, Patricia Rangel Sobral Dantas1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Acute myocardial infarction is when an obstruction of the coronary artery leads to oxygen deficiency in the myocardial supply, causing necrosis1. According to the Ministry of Health records, there was an increase in the occurrence of AMI in young people (aged 20 to 39 years) and a potential responsible for these cases, which despite being considered small when compared to the national context, are the unhealthy lifestyle habits associated with physical inactivity2. Infarctions in young people are more lethal due to the rapid evolution and their exuberant clinical condition. If there is a delay in starting treatment, complications such as heart failure and arrhythmias may occur2,3. Objectives: To analyze the panorama of the occurrence of AMI in people aged 20 to 39 years. Methodology: A literature review and an observational, descriptive, and cross-sectional collection of data on the occurrence of AMI, available at DATASUS - SUS Hospital Information System - December 2004 to December 2018, were carried out. Results: In the analyzed period, if 45,883 hospitalizations for acute myocardial infarction in people aged between 20 and 39 years, where the year responsible for the largest number was 2018, with 3,823, followed by 2017 with 3,778; on the other hand, the lowest number was 2004 with 2,351, followed by 2005 with 2,518. The total number of deaths was 2,704 in 15 years studied. As for sex, 33,462 affected males while 12,421 were females. The Southeast with 23,901 cases, the Northeast with 8,139, the South with 8,088, the Midwest with 3,295, and the North with 2,460. Among the federation units, Sao Paulo led with 13,377 hospitalizations. As for the character of the hospitalizations, 33,289 were considered urgent, where they obtained 1,946 deaths (mortality rate of 5.85), the electives totaled 2,373 with 73 deaths (mortality rate of 3.08) and for other causes, 3 with 50% mortality rate. Of the 1946 deaths in emergency care, 1,569 were in patients aged 30 to 39 years, corresponding to 80.6% of cases. Conclusion: It was possible to observe the percentage increase of 62% of the cases of AMI in individuals aged 20 to 39 years in 10 years, where 72.5% was attended to on an urgent basis, which obtained the highest mortality rate, mainly in the age range from 30 to 39 years. It is a disease prevalent in males, which accounts for 72.9% of cases. Where Sao Paulo has more than half of admissions across the Southeast. 109765 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Impact of the COVID-19 Pandemic on the Performance of Myocardial Revascularizations using Extracorporeal Circulation in the State of Rio de Janeiro GIULIA VITORIA NASCIMENTO DA SILVA1, GABRIEL REZENDE NEVES1, LUCAS DIAS SILVA1, SAMARA GUILHERMINA DE SOUSA1, PAULO CESAR LOBATO MAGALHAES2, LETICIA RIBEIRO DOS SANTOS1, MARIANA DOS SANTOS GUIMARAES2, LARISSA DACIER LOBATO COMESANHA2, TEREZA MARIA MEIRELES FERNANDES DA SILVA1, MARCONDES TAVARES NEVES JUNIOR1 (1) Universidade do Estado do Para (UEPA); (2) Universidade Federal do Para (UFPA) Introduction: Due to the COVID-19 pandemic, logistical changes have occurred to meet the demand of patients affected by the SARS-CoV-2 virus. However, the expansion of beds for the hospitalization of infected people and the suspension of elective surgeries contributed to modifying the profile of cardiovascular interventions performed during the period. Objective: To analyze the impact of the COVID-19 pandemic on myocardial revascularization using extracorporeal circulation in the state of Rio de Janeiro (RJ). Methods: Observational, cross-sectional, analytical-descriptive and quantitative study. The numbers of myocardial revascularization surgeries using extracorporeal circulation, in RJ, from 2019 to 2021, were obtained via DATASUS - Hospital Information System of the Unified Health System (SIH/SUS). The amount of confirmed COVID-19 cases per month in RJ, from March 2020 to December 2021, were collected via Painel COVID-19 - the virtual platform of the Secretary of Health of the State of Rio de Janeiro. Results: COVID-19 cases in RJ emerged in March 2020 and the number of notifications grew abruptly in May, a period in which there was an increase of 44,687 cases when compared to the previous month. During this period, 77 myocardial revascularizations were performed with the use of extracorporeal circulation, 37.4% less than in the same month of the previous year. In May 2021, the second month with the highest number of new cases of infections in RJ throughout the pandemic, 88 procedures were performed, representing an increase of 14.3% when compared to the same month in 2020 and a decrease of 28.4% compared to the same period in 2019. In addition, in September 2021, the period with the highest peak of new cases of COVID-19 in RJ, 97 myocardial revascularizations were performed, 6.7% more than the same month in 2020 and 33.1% less than in 2019. September 2021 values were succeeced by only 64 procedures in the following month, October 2021, which configured a 34% decrease in surgeries performed between these months. Comparing October 2021 with the same month in 2020, there was a reduction of 27.3%, and in relation to the same period in 2019, a decrease of 56.7%. Conclusion: In view of the increase in cases of COVID-19, there is a significant decline in the volume of myocardial revascularization surgeries performed in the state of RJ, consequently hindering the medical therapy of atherosclerotic coronary disease. 109769 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Jugular Vein Ultrasound: A Central Venous Pressure Predictor for Patients Hospitalized with Heart Failure - a Systematic Review CAIO PLUVIER DUARTE COSTA1, Mayara Gabriele Toledo1, Eduardo Thadeu de Oliveira Correia1 (1) Universidade Federal Fluminense Introduction: Monitoring volume status in patients hospitalized for heart failure (HF) is fundamental to provide therapeutic and prognostic guidance. Recently, the measurement of the internal jugular vein (IJV) by ultrasonography has been object of investigation by several studies. Therefore we aim to systematically review if IJV ultrasound is an useful parameter to predict central venous pressure (CVP) in patients hospitalized for HF. Methods: We conducted a systematic review following the PRISMA guidelines. Original studies indexed by Embase, Pubmed, Cochrane and LiLACS with the keywords: "ultrasound" or "ultrasonography" and "heart failure" and "jugular vein" published until March, 2022 and which matched the inclusion criteria were included. Two authors (C.P and M.T.) performed the screening and data extraction, in cases of discordance, a third author (E.T.) made the decision. Results: Thirteen studies were included, with a total of 898 patients analyzed. Due to the significant heterogeneity between studies, a meta-analysis was not conducted. In all included studies CVP was measured by right heart catheterization. For the ultrasound evaluation of CVP, 5 used the diameter of the IJV; another 4 used the cross-sectional area (CSA) of the IJV and 4 studies used the height of IJV collapse and added 5 centimeters to this measurement (uJVP). Studies that analyzed the diameter of the IJV showed an AUC of 0,74 to 0,84 to predict CVP. Regarding CSA, all 4 articles showed that the IJV ultrasound was useful to predict CVP. Zamboni et al. showed that the CSA was 50-60% better than clinical visualization of jugular vein, while Simon et al. demonstrated an AUC of 0,86 for a CSA variation higher than 66% during Valsalva, compared with rest. Moreover, for the uJVP method, all the included studies concluded that it was a significant predictor of CVP. Significantly, Wang et al. showed that uJVP was a significant predictor of CVP in obese patients, with an AUC of 0,81, although it had a better accuracy among non-obese patients. Conclusion: This systematic review shows that IJV ultrasound is a significant predictor of CVP measured by right heart catheterization. Also, this demonstrates the need for a standard ultrasonographic measurement method of the IJV, to diminish the heterogeneity of future studies. In conclusion, this study paves the way for future randomized trials that aim to investigate if IJV ultrasound can be used to guide diuretic therapy and discharge. 109776 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Echocardiographic Profile of Patients with Resistant Arterial Hypertension: Preserved or Reduced Ejection Fraction? OSVALDO CARLOS SILVA LEOPOLDINO1, Osvaldo Carlos Silva Leopoldino1, Camila Orge Rodrigues2, Jayne Milly Queiroz Santana1, Bernardo Oliveira Torres3, Juliana Almeida Frank3, Amanda Gabriela Rodrigues dos Santos de Souza1, Pedro Henrique Souza de Aragao3, Ana Luisa Soares Chiaretti3, Victoria Valadares Andrade3, Cristiano Ricardo Bastos de Macedo4, Roque Aras Junior4 (1) Universidade Salvador (UNIFACS); (2) Escola Bahiana de Medicina e Saude Publica (EBMSP); (3) Universidade Federal da Bahia (UFBA); (4) Hospital Universitario Professor Edgard Santos (HUPES) Introduction: The relationship between hypertension and diastolic dysfunction with preserved ejection fraction (EF) is well established, yet this data is still nebulous in patients with Resistant Arterial Hypertension (RAH). It is uncertain whether other particulates in this group, such as high afterload, may interfere with EF or diastolic dysfunction. Objectives: Analyze the epidemiological and echocardiographic profile of patients with RAH. Methods. Open, Transversal, and Unicenter study from a University Hospital set in Brazil from June 2018 to March 2022 (last update). Eligible patients were those over 18 years and diagnosed with RAH (defined as medical office Blood Pressure (BP) >=140/90 mmHg despite the use of >=3 antihypertensive drugs, one of those being a diuretic, or controlled BP using >=4 medication). Statistical tests (Chi-square test and Z-test) and dispersion measurements were performed using the graph pad and SPSS app. The BP was taken by standardized automated devices, and the echocardiographic exam was performed by the hospital's staff. Results: There were evaluated 118 hypertensive patients, mostly black (n = 64) and brown (n = 48), with a mean age of 65.28 (+-11.14) years and a predominance of women (n = 91). The mean systolic/diastolic BP values were 143.6 (+-22.09 [P < 0.01])/82.98 (+-16.42 [P < 0.01]) mmHg. At the echocardiographic, the mean EF was 66.00% (+-13.05 [P < 0.01]), with only 6 (5.08%) having EF < 40% and 6 (5.08%) with EF 40-50%. The interquartile range of EF (Q1-Q3) was 9,19. Of this sample, 63.5% (n = 75) manifested diastolic dysfunction, with 93.33% (n = 70) being type 1 dysfunction and 6.66% (n = 5) type 2. Regarding the clinical profile, 55 patients declared themselves sedentary, 73 presented with metabolic syndrome, 23 with Chronic Kidney Disease, and 48 with Type 2 Diabetes Mellitus. Conclusion: This study presents some limitations, such as the low sample size and the echocardiogram limit (it is operator-dependent). Nevertheless, this work shows a high prevalence of preserved EF at the echocardiogram, revealing preservation of the left ventricle systolic function. A large proportion of the population had diastolic dysfunctions at an initial state, suggesting that, despite the severity of hypertension, the compromise to the cardiac functionality occurs at a rather late point in the natural history of the disease. At last, some individuals had low EF which suggests independent factors for systolic impairment. 109788 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Deaths by Heart Failure in Northern Brazil in 2020 LEANDRO LOURENCO SILVA MONTEIRO1, Luiz Fernando Leite da Silva Neto1, Luig Matias Barreiros Pires2, Ana Beatriz Rezende dos Santos Correa2, Talles Levi Pereira Nogueira3, Ana Paula Correa de Lima2, Igor Lucas Farias Lima1, Fernando Tavares Brasil Teixeira1 (1) Universidade do Estado do Para (UEPA); (2) Centro Universitario do Estado do Para (CESUPA); (3) Universidade Federal do Para (UFPA) Introduction: Cardiac Insufficiency, marked by heart failure in blood pumping, is still a common outcome for heart diseases of several etiologies and, despite optimized therapy, maintains high levels of hospitalization and in-hospital mortality of patients. In this sense, cardiac insufficiency has a high impact, since social determinants such as gender, age and socioeconomic conditions influence the clinical outcome of disease. Objective: To trace the epidemiological characteristics of deaths by Heart Failure in the Northern region of Brazil in 2020. Method: The study has ecological, descriptive and retrospective character. Data were collected from the Departamento de Informatica do Sistema Unico de Saude (DATASUS) in the Sistema de Informacao sobre Mortalidade (SIM) as to the number of deaths by Heart Failure in the Northern Region, and epidemiological characteristics of patients, in 2020. The following variables were analyzed: number of deaths, federation units, gender, age group, race/color, schooling and location. Results: In 2020, 1.510 deaths were recorded. The Federation Units with highest records are from Para (46,42%), Amazonas (17,68%) and Rondonia (15,56%), and Amapa with the lowest value (2,98%). Relating to age groups, the most prevalent were over 80 years (39,07%), 70 to 79 years (25,58%) and 60 to 69 years (18,27%). In addition, men received quantitative prominence with 58,14%. Regarding race/color, the most notified were brown (65,29%) and white (22,58%). A significant number of deaths occurred in individuals without schooling (32,05%), followed by 1 to 3 years of schooling (21,45%) and 4 to 7 years (16,88%), with the lower value in the classification corresponding to school formation over 12 years (3,5%). Finally, most occurred in a hospital environment (73,04%), followed by home location (19,4%). Conclusion: Cardiac Insufficiency is a disease with a five-year survival rate that is worrisome, because it generates functional loss and quality of life, gradually and eventually evolving to death. And yet, it is possible to notice that death from Heart Failure is prevalent in the Northern region, whose epidemiology is mainly related to age, gender, race/color and intra hospital environment according to data collected from DATASUS. Therefore, it is confirmed the importance of identifying the epidemiological characteristics of deaths for the implementation of effective public health policies in the prevention of such a pathology. 109795 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION The Influence of Systemic Arterial Hypertension on the Pathophysiology of Acute Aortic Dissection DAVI DE SOUZA CATABRIGA1, Lucas Dalvi Armond Rezende2, Janaina Rodrigues Barbosa1, Beatriz Contarini Peluzzo Moraes1, Caio Lucas Franco Inocencio1, Lorena Padua de Moura Duarte3, Karolini Zuqui Nunes2 (1) Higher School of Sciences of the Santa Casa de Misericordia de Vitoria - EMESCAM; (2) Nursing Department, Health Sciences Center, Federal University of Espirito Santo - UFES; (3) Vila Velha University - UVV Introduction: Systemic arterial hypertension (SAH) is a risk factor for several diseases, including acute aortic dissection (AAD). AAD is defined by the entry of blood into the aortic wall, usually between the outer third and the inner two thirds of the tunica media, due to rupture of the intima. Objective: To elucidate the pathophysiology of aortic dissection and its relationship with systemic arterial hypertension, through the guiding question "What is the pathophysiological relationship of acute aortic dissection with hypertension?" Methods: A systematic review was performed, without meta-analysis, using the PRISMA protocol. Thus, the PubMed database and the Virtual Health Library (BVS) were used during the period of May 2021. The DeCS/MeSH descriptors ""Aneurysm, Dissecting", "hypertension" and "Pathophysiology" were used. combined using the Boolean operator "AND". Results: A total of 270 articles were found; of which, after applying the criteria for inclusion, exclusion of duplicates and exclusion by analysis of title, abstract and full text, 13 articles remained for analysis, all in English. AAD comprises the rupture of the tunica intima, which causes an infiltration of blood into the tunica media, so that this blood continues to flow and creates a false lumen. SAH decreases the blood flow to the vasa vasorum, responsible for nourishing the middle layer of the aorta. This situation results in an increasing stiffness of this vessel, which can cause a degeneration of the middle layer of the aorta and increase shear stresses, situations that favor the AAD. This degeneration involves mechanisms of loss of smooth muscle cells and cellular matrix and production of pro-inflammatory cytokines and metalloproteins. On the other hand, the rupture is related to sites exposed to greater shear stresses, which promote an endothelial alteration that delays the proliferative, apoptotic and remodeling processes of the aorta. Conclusion: It was found that the pathophysiological mechanism of AAD of hypertensive etiology is the degeneration of the aortic middle layer and the increased shear stress. These factors are caused by reduced flow of vasa vasorum, loss of smooth muscle cells, production of pro-inflammatory cytokinins and metalloproteins, and changes in proliferative, apoptotic and remodeling processes. We emphasize the need for further research on the pathophysiology of this process in order to define a better diagnostic and therapeutic approach to AAD. 109817 Modality: E-Poster Scientific Initiation - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Spirituality and a New Look at Takotsubo Syndrome BEATRIZ MONTENEGRO OLIVEIRA1, Dra. Antoinette Oliveira Blackman1, Adda Cecilia Batista de Carvalho Vieira1, Andre Luiz Vergamini Dias2, David Ricardo Bernal Lima Hernandez1, Felipe Romerio Marques Duraes Barbosa1, Maria Gabriela Alves da Silva1, Patricia Brito de Almeida Borges1, Pedro Henrique Alves Miranda1, Suellen Keyze Almeida Lima1, Warllson Jesus dos Santos1, Wenderval Borges Carvalho Junior3 (1) Centro Universitario do Planalto Central Apparecido dos Santos; (2) Universidade Nove de Julho; (3) Hospital Universitario de Brasilia Introduction: Takotsubo Syndrome (TS), characterized by transient systolic dysfunction of apical contraction, which simulates Acute Myocardial Infarction (AMI) without obstruction in the corresponding territory, has in its management focus on pharmacological treatment. The pathogenesis is not completely known and the mechanisms suggested are: coronary spasm, microvascular dysfunction and excess of catecholamines, the latter being triggered by emotional stress. Thus, special attention must be given to the integral health of patients, corroborating the concept of health of the World Health Organization (WHO). Objective: To highlight the importance of Spirituality in the complementary management of TS. Methods: Narrative review with search in Pubmed and Scielo databases including case reports, cohort studies, randomized clinical trials and systematic reviews about TS in Portuguese and English languages. Results: Data on non-pharmacological treatment of TS are limited and do not show a relationship between spirituality and TS. Initially more prevalent (90%) in women with a mean age of 68.5 years, with the pandemic of COVID-19 there was an increase in prevalence in men (about 30% of cases), due to stress caused directly by myocardial injury resulting from SARS-CoV-2 or indirectly by the socioeconomic influences of the pandemic. The INTERHEART study (conducted in 52 countries) assessed the impact of cardiovascular risk factors for AMI and found that psychosocial factors (stress, depression, and life events) have a 32.5% risk. The PEACE-III study with post-AMI patients and positive psychology interventions showed substantial improvement in psychological and behavioral outcomes. For the spiritual anamnesis, we have the FICA, HOPE, SPIRIT and FAITH tools, besides the DUREL index; the FACIT-Sp-12 scale; the WHO quality of life instrument (WHOQOL-SRPB); the Spiritual Well-Being scale; among others, as instruments to assess the dimensions of spirituality. Final considerations: The importance of integrating Spirituality in a systematic way in clinical practice and the expansion of the look at the patient (integrality) to improve cardiovascular outcomes is evident, and the application of the WHOQOL - SRPB to measure the dimensions of spirituality should be enforced. More robust studies in the population in question are recommended in order to explore opportunities for future research on TS integrated with Spirituality. 109818 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Analysis of Hospital Morbidity of Individuals with Primary Hypertension in Northern Brazil from 2017 to 2021 IGOR LUCAS FARIAS LIMA1, Luiz Fernando Leite da Silva Neto1, Wadilla Fiuza da Silva2, Larissa da Silva Cambraia1, Alexandre D'Annibale Cartagenes1, Pietro Chaves Amaral Miralha3, Talles Levi Pereira Nogueira2, Vinicius Queiroz Silva1 (1) UNIVERSIDADE DO ESTADO DO PARA - UEPA; (2) UNIVERSIDADE FEDERAL DO PARA - UFPA; (3) CENTRO UNIVERSITARIO DO ESTADO DO PARA - CESUPA Introduction: Primary Hypertension is the term used to characterize Systemic Arterial Hypertension with no known cause, accounting for about 95% of cases. In this clinical entity, the patient has blood pressure levels that confer a significant increase in the risk of clinical events in the short and long term. As it is a highly prevalent disease, it is necessary to understand the hospital morbidity of this disease in the North region of Brazil. Objective: To characterize the epidemiological profile of patients with hospitalization outcome due to Primary Hypertension in the North region of Brazil between 2017 and 2021. Method: The following study is ecological, descriptive and retrospective. Data were sourced from the Departamento de Informatica do Sistema Unico de Saude (DATASUS) regarding the epidemiological characteristics of hospital morbidity due to primary hypertension in Northern Brazil between 2017 and 2021. The following variables were analyzed: number of hospitalizations, year of hospitalization, federation units, sex, age group, hospitalization cost, hospitalization time and mortality. Results: A total of 28,331 hospitalizations were recorded in the verified period. The main years that received the most hospitalizations were: 2017 (22.24%), 2019 (22.07%) and 2018 (21.99%). As for the federation units, the most remarkable were: Para (57.88%), Rondonia (17.38%) and Amazonas (14.57%). In concern to the profile of the hospitalized patient, the most prevalent were women (56.34%), with the most prevalent age groups from 60 to 69 years old (22.11%) and from 70 to 79 years old (19.66%). Furthermore, the medium cost of hospitalization was R$ 263.06, with an increase of 22.86% from 2017 to 2021. The average hospital internment was 3.3 days, with a higher value for males compared to females. Finally, the mortality rate is 2.02, with emphasis on the age groups over 80 years and 70 to 79 years. Conclusion: Besides noting that the number of hospitalizations showed an uneven distribution among the states in the region, there was an increase in the average cost of hospitalization for the health system during the period. Concerning the profile of patients, most are female, but males had higher mortality, in addition to a clear correlation between age and the outcome of death. This study presents data that can guide not only clinical decisions focused on populations at risk, but also provide the basis for public health actions and resource allocation. 109834 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Correlation between B-Lines After Submaximal Exercise Test and Nt-Probnp in Outpatients with Heart Failure with Reduced Ejection Fraction ALICE ZANETTI DUSSIN1, Anna Paula Tscheika2, Luiz Claudio Danzmann3, Marcus Vinicius Simoes4, Andrielle Dias Pinheiro2, Luiz Carlos Bodanese1 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS); (2) Hospital Sao Lucas da PUCRS (HSL); (3) Universidade Luterana do Brasil (ULBRA); (4) Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP) Background: Congestion detected by lung ultrasound (LUS) through B-lines is related to prognosis in patients with heart failure (HF); performing it after physical stress tests can detect congestion even earlier. However, stress tests require equipment and specialized professionals. The 6-minute walk test (6MWT) is a submaximal exercise test; it is a feasible, inexpensive, and reproducible test to evaluate patients with HF. The dosage of NT-proBNP is also useful in the diagnosis and prognosis of patients with HF. There are no studies evaluating the use of lung US after 6MWT. Aims: To evaluate the correlation of the number of B-lines on LUS before and after the 6MWT with the measurement of the NT-pro-BNP in outpatients with heart failure with reduced ejection fraction (HFrEF). Methods: It is a cross-sectional analytical study with prospective inclusion of patients from three HF outpatient clinics. Inclusion criteria were: age >=18 years, to have the diagnosis of HF for at least 6 months and to have echocardiogram with ejection fraction <40%. Blood samples were collected for NT-proBNP analysis before the 6MWT. Patients were submitted to the LUS before and after 6MWT. Results: From September 15, 2020 to November 30, 2021, 188 patients were included in the study. The mean age of the patients was 61.83 years (+-12.13 years); most patients were male (63.8%); the median left ventricular ejection fraction was 31.73% (interquartile range 25-75% [IQR] 28-37%); the most prevalent etiology of HF was ischemic (52.7%). The NT-proBNP median value was 1,017.5 pg/mL (IQR 331.5-3,482.5); the median number of B-lines was 3 (IQR 1-9) at rest and 6 (IQR 2-13) after submaximal stress. The NT-proBNP value was correlated with the total number of B-lines at rest (r = 0.517; p < 0.001) and after submaximal stress (r = 0.585; p < 0.001), as shown in Figure 1. Conclusion: B-lines in LUS after submaximal stress and at rest were correlated to NT-proBNP in outpatients with HFrEF. Since congestion is one of the main factors that precedes hospitalization, the use of LUS seems to be a useful and easy-to-learn tool to evaluate outpatients with HF. 109839 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Acute Myocardial Infarction and the Single Health System: An Analysis of Hospitalization and Death for this Pathology in Brazil LUIZ FERNANDO LEITE DA SILVA NETO1, Leticia Lima Branco1, Kennedy Medeiros Cavalcante1, Adriano Leitao de Almeida1, Daniel Oliveira da Costa1, Maria Eduarda Silveira Buhrnheim1 (1) Universidade do Estado do Para Introduction: Acute Myocardial Infarction (AMI) is responsible for 12.1% of all cardiovascular diseases (CVD) deaths. This disease is marked by the impairment of the cardiac heart by the minimal blood supply due to total or partial obstruction of a coronary artery. In this context, an expressive severity of the pathology generates hospitalizations and deaths, denoting the need for epidemiological studies in the Brazilian territory to understand its prevalence. Objective: To evaluate the epidemiological profile of hospitalizations and deaths in Brazil due to myocardial infarction from January 2016 to December 2020. Methods: This study has a descriptive, transversal, quantitative and ecological character. Data was collected on Unified Health System Information Department, including information from january 2016 to december 2020. Thus, there were analyzed variables such as hospitalization year, region, sex, age group, color, type of care and deaths. Results: There were a total of 600.752 hospitalizations by AMI. The higher prevalence was found in the Southeast region (49,47%). Regarding the most affected group of people, white people (40,98%), from male sex (56,02%) and aged between 60 and 69 years old (30,75%) were in evidence. Furthermore, the hospitalization quantity increased from 2016 to 2019, although it decreased in 2020. Finally, most hospitalizations were categorized as emergencies (95.88%), and the number of deaths represented 10.31% of the total hospitalizations. Conclusion: Hospitalizations caused by AMI increased from 2016 to 2019 due to demographic transition, characterized by a life expectancy increase in the population. However, there was a decrease in cases in 2020 due to the COVID-19 pandemic, marked by a reluctance to seek medical care and structural limitations in hospital centers, hampering notification. Therefore, with these epidemiological data, it is possible to determine populations at risk and the location with the highest prevalence, guiding future research in this area and the creation of public health actions as well as new financial investments. 109850 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOGERIATRICS Resistance Exercises and Pressure Control in Hypertensive Elderly: A Systematic Review BRENO VINICIUS DIAS DE SOUZA1, Lauanda Enia de Medeiros Rocha1, Emilie Queiroga Queiroga1, Gerson Barbosa do Nascimento1 (1) Universidade Federal do Rio Grande do Norte (UFRN) Introduction: Systemic Arterial Hypertension (SAH) is one of the main risk factors for cardiovascular diseases, which can lead to severe complications, target organ damage (TOD) and death, especially in the elderly. The disease control and consequent prevention of complications requires changes in lifestyle, with adherence to appropriate physical exercises for the age group. Objective: To review, based on the scientific literature, the impact of resistance exercise on blood pressure reduction in elderly hypertensive individuals. Method: Systematic review of articles published between 2011 and April 2021, in the BVS, LILACS, Cochrane and Pubmed databases with the descriptors "hypertension"; "resistance training" and "elderly", with 579 articles found. There was the exclusion of duplicate articles, independent evaluation by two researchers of title and abstract, and analysis of the full text of original studies, according to the inclusion and exclusion criteria. Results: 10 articles were included and analyzed. All were unanimous in defending the safety of strength training in hypertension and 9 attested to its direct hypotensive effect in the elderly. The evaluation of resistance exercise in elderly hypertensive women stands out, with a relevant reduction in systolic blood pressure (BP). A 2016 study attested chronic reduction in systolic, diastolic and mean BP in women who acutely already had the hypotensive effect, establishing a relationship between them. It was also evidenced that the greater the duration or volume of exercises, the greater the hypotensive effect. These findings are in line with Brazilian Directive on Arterial Hypertension's recommendations. Conclusion: Within the complexity of SAH treatment, the practice of resistance physical exercises was crucial for blood pressure control. Last decade's studies with methodological rigor confirmed its role in the non-drug treatment of SAH, with safety, reduced BP and improvement in the hemodynamic profile in the elderly. 109852 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Trend of Deaths from Valvular Heart Diseases in Brazil from 2000 to 2019 RENAN GERONIMO SOUZA DA SILVA1, Renan Geronimo Souza da Silva1, Alexandre Akio Majima1, Ana Paula Cassetta dos Santos Nucera1, Fabio de Souza1, Wilson Braz Correa Filho1, Eduardo Marinho Tassi1, Davi da Silveira Barroso Alves1, Paulo Henrique Godoy1 (1) Federal University of the Rio de Janeiro State (UNIRIO) Introduction: Prevalence of heart valve diseases (HVD) is increasing and its etiological profile has changed over the last few decades. Objective: To analyze the trend of deaths due to HVD, according to gender and age group in Brazil, from 2000 to 2019. Method: Ecological study, in which information was collected from the Mortality Information System. The causes of death were categorized into: rheumatic valve disease (RVD); non-rheumatic valve disease (NRDV) and congenital valve disease (CVD), according to ICD-10. Age groups were: 0-29, 30-59, 60 or older. Crude and standardized rates were estimated according to sex and age. Results: A total of 113,570 deaths due HVD were found, 54.93% were female. The distribution by causes was: RVD - 36,018, RVD - 71,477 and CVD - 3,583. The female gender was predominant in the RVD, while in the CVD the male gender was prevalent. In the DVNR, the standardized rate was higher in males, although a greater magnitude of deaths occurred in females. The highest mortality rates due DVR and DVNR were observed in the group aged 60 years and over. In CVD, the mortality rate was higher in the younger age group. The trend for deaths due DVNR and CVD was increasing, while from DVR was decreasing. Conclusions: Trends in deaths from RVD and NRVD seem to reflect an epidemiological transition from these causes. The trend for DVC deserves attention. It seems to reflect higher mortality from congenital heart disease in the country. 109859 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Temporal Analysis of Mortality Rate and Hospital Profile of Hospitalized Patients with Systemic Arterial Hypertension in Brazil between 2012 and 2021 HILDEBRANDO ANTUNES DE CARVALHO NETO1, Bruno Oliveira Souza Prates1, Beatriz Souza Martins1, Beatriz Catarina dos Santos de Oliveira1, Gabriela Chateaubriand Campos1, Rafael Carlos Pereira1 (1) Universidade Federal da Bahia - UFBA Introduction: Systemic Arterial Hypertension (SAH) is a chronic multifactorial condition that constitutes the main modifiable risk factor for cardiovascular complications. It is estimated that this disease has high morbidity and mortality and affects about 30% of the world's adult population, with higher prevalence in middle-income countries, such as Brazil. In this sense, the epidemiological study of the disease presents itself as an important instrument for this control and prevention. Objective: To analyze the mortality rate and epidemiological profile of hospitalized patients with SAH in Brazil, between 2012 and 2021. Methods: This is an ecological time series study from secondary data collected by the Hospital Information System (SIH-SUS), between the years 2012 to 2021. The total and percentage distribution of elective and urgent care, mortality rate and demographic data were included. Results: In Brazil, in the years analyzed, 608,045 cases of patients hospitalized for SAH were reported, 93.9% of which were on an emergency basis. The year 2012 had the highest number of cases (85,646), and year 2021 had the lowest number (35,472). Females were the most prevalent (85.75%) and the age group most affected was the elderly between 60 and 69 years old (22.42%), followed by elderly people between 70 and 79 years old (20.34%). Most of the admissions were of brown patients (38.38%), followed by whites (24.24%). Within the years under review, the mortality rate ranged from 1.41 in 2012 and 2013 to 2.1 in 2021. Conclusions: Based on the data analyzed in a temporal sequence, there is a tendency to decrease the number of hospitalized patients each year, with the year 2021 having a total number of hospitalizations 58.58% lower than the beginning of the historical series. This decrease in hospital admissions happened gradually, and had its most significant drop in 2020 (24.99%). Elderly, female and brown patients had a higher prevalence in all analyzed years. Regarding the mortality rate attributed to SAH, among hospitalized patients, there was a trend towards stability, with an increase in the year (27.27%). 109863 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY The Impact of Vericiguat as a Reducer of Mortality and Hospitalization in Patients with Heart Failure with Reduced Ejection Fraction: A Systematic Review ENZZO BARROZO MARRAZZO1, Luiz Fernando Moraes Pereira1 (1) Pontificia Universidade Catolica de Minas Gerais Background: Heart failure (HF) is occasioned by a functional or structural cardiac change. HF has been during years the major cause of mortality in the world. The treatment of chronic heart failure with reduced ejection fraction is mainly diuretics, neurohormonal antagonists and devices therapies. New pharmacological therapies have been developed as sodium-glucose cotransporter 2 inhibitors and vericiguat, which are promises a better prognosis. Aim: To clarify the impact of Vericiguat use on mortality and on hospitalization rates of patients with heart failure with reduced ejection fraction. Methods: A systematic review was carried out by using a sheared in the PubMed, Lilacs, and Embase databases to search for the descriptors "Vericiguat" e "Heart Failure, Reduced Ejection Fraction". Only studies conducted on humans, clinical trials where participants were over 18 years old had been selected for inclusion. Studies, where was including patients with HF with preserved ejection fraction and studies focused on sacubitril/valsartan, were not included. To avoid bias was made a double-check in the entire filtering process by different authors. Results: A total of 116 articles were identified and analyzed, of which only 7 were eligible for this review. The use of vericiguat after 3 months of follow-up demonstrated a decrease in the incidence of cardiovascular deaths or hospitalization for HF, reducing these primary outcomes by 4.2 events per 100 patient-years. Despite the few studies, it is suggested that these results can be generalized to patients with worsening HF events in clinical practice. Furthermore, the use of vericiguat was not related to the occurrence of atrial fibrillation events after randomization, although these events are related to the number of deaths and hospitalizations for HF. The effect of vericiguat on the assessed outcomes appears to be better in younger patients, however there is no heterogeneity in the treatment effect of vericiguat compared to placebo on the composite primary endpoint of patients according to baseline systolic blood pressure. Conclusion: The use of vericiguat appears to be promising in reducing mortality and hospitalization rates in patients that developed HF with reduced ejection fraction. Despite recent and scarce studies, the drug demonstrates good safety in clinical management, not inducing the occurrence of events such as syncope, clinical manifestations resulting from hypotension and atrial fibrillation. 109868 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of the COVID-19 Pandemic on Mortality from Heart Failure in Southern Region of Brazil LARISSA ALMEIDA BUSNELLO1, Paola Goncalves Moreira de Oliveira1, Bruna Karas1, Ana Carla Dlugosz1, Alice Magro Koscianski1, Francielle Nocera Viechineski1, Camilla Mattia Calixto1, Julia Henneberg Hessman1, Mario Claudio Soares Sturzeneker1 (1) Universidade Estadual de Ponta Grossa (UEPG) Introduction: Heart failure (HF) has an estimated worldwide prevalence of 1-2%, reaching >=10% in elderly people >=70 years. In Brazil, hospitalizations for HF correspond to 4% of general hospitalizations and have high morbidity and mortality. During the COVID-19 pandemic, there was congestion of the health system, but during the 2nd half of 2021, about 70% of the population was vaccinated with the 1st dose and 40% with the 2nd dose. Objective: Evaluate the impact of the pandemic on HF mortality in the southern region of Brazil through the analysis of DATASUS data. Methods: Data regarding HF in the South region were collected in the DATASUS system: hospitalizations, deaths and average hospital stay. Lethality was calculated by dividing the number (N) of deaths by the N of hospitalizations. The periods of pre-pandemic (02/17-02/20), pandemic (03/20-06/21), peak of the pandemic (12/20-05/21), 1st and 2nd quarter of the peak (12/20-02/21 and 03-05/21) and mass vaccination (06-12/21) were evaluated. The means of each variable were calculated by sex and age, and each vaccination period was compared with the others, with the results manifested as a percentage. Results: There was a reduction in the number of hospitalizations in the period of mass vaccination in relation to the pre-pandemic period (25.88%) and an increase of 44,76% in comparison with 2nd trimester of the peak (2TP), and about hospitalizations and deaths, the largest percentage difference evaluated was seen in the 2TP. The evaluation by gender and age groups showed similar behaviour, including the largest increase in relation to the peak of the pandemic, reaching 55.06% in the population >80 years. Regarding the average hospital stay, there was an increase in the vaccination period compared to all other periods, except in the 20-29 age group. Regarding deaths, during the mass vaccination period, there was little variation when compared to the pre-pandemic period, but with significant increases compared to pandemic periods, especially when compared to the peak. There was a significant increase in lethality during the vaccination period when compared to the pre-pandemic period (39.42%), mainly in the age group of 40-49 years (62.43%) and 60-69 years (59.99%). Conclusion: Hospitalizations and inpatient deaths reduced during the COVID-19 pandemics, especially at the peak of the pandemy. However, currently, with mass vaccination, there is a tendency to return the parameters to pre-pandemic values. 109869 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Impact of the COVID-19 Pandemic on Morbidity and Mortality from Heart Failure in the Southeast Region of Brazil ANA CARLA DLUGOSZ1, Larissa Almeida Busnello1, Camilla Mattia Calixto1, Bruna Karas1, Julia Henneberg Hessman1, Alice Magro Koscianski1, Mario Claudio Soares Sturzeneker1, Paola Goncalves Moreira de Oliveira1, Francielle Nocera Viechineski1 (1) Universidade Estadual de Ponta Grossa (UEPG) Introduction: The SARS-CoV-2 pandemic may have influenced heart failure (HF) morbidity and mortality due to a lack of vacancies or fear of contamination in the hospital. Objective: Assess the influence of the SARS-CoV-2 pandemic on HF morbidity and mortality in the Southeast region. Method: Data from 2017 to 2021 were collected on the DATASUS platform. Lethality was calculated by dividing the number (N) of deaths by the N of hospitalizations and expressed as a percentage. The periods denominated pre-pandemic (02/2017 to 02/2020), pandemic (03/2020 to 06/2021), peak of the pandemic (12/2020 to 05/2021), the peak's 1st and 2nd quarter (12/2020 to 02/2021 and 03/2021 to 05/2021) and mass vaccination (06/2021 to 12/2021) were evaluated. The means of each variable were calculated in general by sex and age group. The pre-pandemic and mass vaccination periods were compared to the others, and the results were expressed as a percentage. Results: Compared to the pre-pandemic period, there was a reduction in the number of hospitalizations in the pandemic period (20.56%), mainly at the peak (34.31%). There was a reduction in the average hospitalization length in all periods of the pandemic, except for the 20-29 age group in the peak's 1st quarter. There was also a reduction in deaths numbers, mostly in the peak's 2nd quarter. There were increases in lethality in all periods of the pandemic. During the mass vaccination period, there were reductions in hospitalizations (15.77%), hospitalization length (3.05%) and mortality (3.06%) compared to the pre-pandemic period. However, compared to the pandemic period, there was an increase in hospitalizations (6.03%), hospitalization length (3.96%) and mortality (11.12%). As for lethality, there was an increase of around 15% in both genders and in all age groups compared to the pre-pandemic period and 6.32% compared to the pandemic period, except for women. Conclusions: Data suggests a significant impact of the pandemic on HF lethality in the Southeast region. The expressive reduction in the number of hospitalizations, associated with the reduction in the average hospitalization length, could justify a lower number of deaths and the divergent behaviour of lethality during the pandemic. Mass vaccination allowed these patients to have greater access to hospitals and, probably due to the increase in demand caused by the pandemic, there was an increase in hospitalizations, hospitalization length and mortality. 109874 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hospitalization and Mortality Index on Acute Myocardial Infarction in Brazil in the Last Decade MARIANA SALLES BALLALAI1, Helena Raquel Nogueira de Oliveira1, Isabela Aragao Colares1, Gabriel Sousa Santos1, Renata Pinheiro Martins de Melo1, Gabriel Coelho Brito Dias1, Jose Levi Tavares Cavalcante1, Ane Karoline Medina Neri2, Weiber Silva Xavier3, Joao Luiz de Alencar Araripe Falcao1, Sandra Nivea dos Reis Saraiva Falcao1 (1) Faculdade de Medicina, Federal University of Ceara (UFC); (2) Hospital Universitario Walter Cantidio (HUWC), Federal University of Ceara (UFC); (3) Programa de Educacao em Reanimacao Cardiorrespiratoria (PERC) Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Acute chest pain is responsible for more than 5% of all emergency department visits. Although most of these patients are discharged with a diagnosis of non-cardiac cause, about 25% are affected with acute myocardial infarction (AMI). Objectives: To analyze the behavior of hospitalizations and deaths numbers due to acute myocardial infarction in the last decade in Brazil. Methods: Retrospective descriptive study with data from the Brazilian Unified Health System database(Tabnet-DATASUS) on hospital admissions and deaths from AMI, by region, in Brazil, from January 2012 to January 2022. Results: Annually, an average of 107,522.8 (+-17,350.5) hospitalizations due to AMI occur in Brazil, and the southeast region has the highest average number of hospitalizations (55,005 +- 8003.8). There was an increase of 64% in the number of hospitalizations in 10 years, except in the year 2020 when there was a discrete reduction of 0.6%, which could be explained by the pandemic context. The most considerable increase occurred in the mid-western region, with 160.7% increase in the number of hospitalizations, followed by the northern region with 88.1%. On the other hand, the southern region had the shortest variation, with an increase of 51.7% in 10 years. About mortality, an average of 11,981.4 deaths (+-936.26) occurred annually due to AMI. In the last decade, there was an increase of 28% in the number of deaths, except for the intervals 2016/2017 and 2019/2020, in which there was a subtle reduction respectively of 2.0% and 3.8% in the numbers of deaths. The period of greatest increase was 2020/2021 (8.6%). The region with the highest increase in mortality was the mid-west (37.8%). Although the Southeast region had the highest percentage of deaths, this region had the lowest variation in the number of deaths over the years (22.8%). Conclusion: We analyzed the numbers of hospitalizations and deaths due to AMI in the last decade and we found that AMI is still very prevalent in Brazil and that it is an important cause of death in this country. We also noted that there was a considerable increase in hospitalizations during the evaluated period, especially in the southeastern region. Thus, a greater strict prevention in populations at risk is necessary, and the importance of early recognition and adequate treatment of these patients is reaffirmed, to avoid worse prognosis. 109876 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Congenital Coronary Fistula: The Diagnosis Method and Its Treatment, An Experience After Correction with Minimally Invasive Videothoracoscopy BRENDA GABRIELE SMANIOTTO RAULIK1, Jeronimo Antonio Fortunato Junior2, Juliana Fortunato2, Shema El-laden hammoud1, Leticia Gusso Scremin1, Nikolai Cernescu Neto1, Gabriel Fontana de Melo1, Thaisa Rodrigues Ferreira Basaglia1 (1) Universidade Positivo; (2) Hospital da Cruz Vermelha Brasileira - Filial Parana Introduction: Coronary artery fistula (CAF) is defined as an abnormal communication of coronary arterial blood with other capillary structure, without passing through myocardial capillaries. The congenital origin is the most common, despite accounting for only 0.2 to 0.4% of congenital heart defects. Although rare, they can be fatal. Cardiac surgery allows the correction of most coronary anomalies, but thoracotomy and cardiopulmonary bypass support are associated with a higher number of postoperative complications compared to less invasive videothoracoscopy techniques of surgical treatment. Objectives: Report 5 cases of patients diagnosed with CAF and describe the methodology used for diagnosis, the 5-year evolution of the patients, and the description of the first cases reported in the literature who underwent minimally invasive video-assisted thoracoscopic surgery (VATS). Methodology: We selected the medical records of five medical with CAF diagnosed by two-dimensional echocardiography, coronary angiotomography and cineangiocoronariography. Results: Patients who underwent VATS procedure had to sign an Informed Consent Form. In this study the male gender was more frequent, with 82% of cases, and the mean age was 56.8 years. All patients presented clinics of obstructive coronary insufficiency and only one patient evolved to heart failure NYHA III functional class, this same patient in angiographic studies presented, besides the CAF, an intramyocardial tract of the anterior descending artery. There were no intercurrences during the procedures and the primary success was confirmed with coronary angiographic studies to evaluate remaining fistulous branches or residual shunts. There was no mortality after 5 years of outpatient follow-up. Conclusion: The association of 3 diagnostic methods has fundamental importance to guide the treatment to be followed. With the minimally invasive technique and ligation of the CAF via thoracoscopy, there is a satisfactory surgical result, associated with better long-term clinical outcome and low morbidity. 109900 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Preliminary Analysis of the Satisfaction Level and Perception of Change in the use of an Adapted Diving Mask for Non-Invasive Ventilation Evaluated by the Global Perception of Change (PGIC) in the Postoperative Period of Cardiac Surgery EDUARDA CHAVES SILVEIRA1, Mariana Goulart Almiron3, Jessica Luiza Pedroso da Silva1, Bruna Diehl1, Tiago da Rosa Rambo1, Helena Rocha Machado3, Alexander Romao Vieira Morinelli1, Patricia Erika de Melo Marinho2, Dulciane Nunes Paiva1 (1) Universidade de Santa Cruz do Sul (UNISC); (2) Universidade Federal de Pernambuco (UFPE); (3) Hospital Santa Cruz (HSC) Introduction: Non-invasive ventilation (NIV) is widely used in the postoperative period (PO) of cardiac surgery (CS) to promote lung reexpansion. The orofacial mask, interface usually used in NIV, can cause air leakage and, in the Covid-19 pandemic, avoid aerosolization to the environment has become a priority focus. The adapted diving mask (Owner Mask) emerged as an alternative NIV interface and its effectiveness has been evaluated. Objective: To assess the satisfaction level and the perception of change in patients undergoing NIV with an Owner mask in the PO of CS. Methods: A cross-sectional study that evaluated patients undergoing coronary artery bypass graft or valve replacement surgery with clinical indication for NIV. The level of satisfaction and the perception of change was assessed using the Patients' Global Impression of Change questionnaire at discharge from the ICU. This instrument classifies the perception of improvement in 7 items: 1 = No changes, 2 = Almost the same, without any visible change, 3 = Slightly better, but without considerable changes, 4 = With some improvement, but the change did not represent any real difference, 5 = Moderately better, with slight but significant change, 6 = Better, and with improvements that made a real and useful difference, 7 = Much better, and with a considerable improvement that made all the difference. Data described in frequency of occurrence. Results: Sample (n = 29; 52% male) had comorbidities such as SAH (66.7%), diabetes mellitus (24.8%), ischemic heart disease (19.4%), CHF (16.7%) COPD (11.1%), dyslipidemia (11.1%) and obesity (11.1%). Of the sample evaluated, 17.2% reported "no changes", 3.4% "Almost the same, no visible changes", 20.7% "Slightly better, but without considerable changes", 10.3% "With some improvements, but the change didn't make any real difference", 10.3% Moderately better, with slight but significant change, 20.7% "Better, and with improvements that made a real and useful difference" and 17.2% reported as "Much better, and with a considerable improvement that made all the difference". Conclusion: The level of satisfaction and the perception of change with the use of the Owner mask went from "Slightly better, but without considerable changes" to "Better, and with improvements that made a real and useful difference" in 41.4% of the sample evaluated. The comparison of these outcomes in relation to the conventional orofacial mask will be carried out with the expansion of the research. 109905 Modality: E-Poster Scientific Initiation - Non-case Report Category: NUTRITION The COVID-19 Pandemic and Adolescents and Children Brazilian Lifestyles: A Cross-Sectional Study, 2020 RAQUEL SANTIAGO VITORINO1, Luana Azevedo de Aquino1, Leticia Martins Raposo1, Simone Augusta Ribas1, Michelle Teixeira Teixeira1 (1) Universidade Federal do Estado do Rio de Janeiro UNIRIO In an overwhelming way, the Sars-Cov2 virus changed the planetary routine starting in 2020. In order to contain the advance and mortality of the pandemic, the WHO and several entities and governments recommended restriction in social contact, resulting from the closing of schools, commerce and leisure areas. The domestic environment becomes the only space for social coexistence, limiting the activities of children and adolescents. The vulnerability of development in this age group maximizes the risks by interrupting the children's routine. Objective: To describe the lifestyle of Brazilian children and adolescents, regarding food, physical activity, sleep quality, screen time, in the period of social restriction resulting from the COVID-19 pandemic. Methods: Cross-sectional study carried out between May and June 2020, with data collected through online forms, intended for parents and/or guardians of children aged 2 to 9 years and adolescents aged 10 to 18 years, in a random and non-probabilistic manner, in all Brazilian regions. Prevalence calculations were performed, with a 95% confidence interval, with the R software. Results: 1309 participated in the survey, 589 children and 720 adolescents. Of the total, half of the families were in social isolation (52%) and belong to the middle social class (56%). As for the practice of physical activity, 72% did not perform or performed less than one hour a day. In addition, the sedentary behavior of excessive use of electronic devices occurred among 75% of those evaluated, with adolescents being the users with the highest reported screen time. There was a change in sleep among 55%, with inadequacy for more (17%) or less (24%). As for eating habits, 30% used to replace meals with snacks, and there was a significant increase in the consumption of sugary drinks (25%), sweets (45%) and quick snacks (36%), especially among adolescents (p < 0.001). On the other hand, there was a reduction in the consumption of beans (10%), fruits (13%), vegetables (20%) and dairy products (10%). Conclusions: The social restriction imposed by the COVID-19 pandemic has imposed negative changes in diet and physical activity level that could possibly have a long-term impact on the health of children and adolescents. 109909 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Ami Hospitalizations in the Current Context of the COVID-19 Pandemic: A Comparative Study between Demographic Regions in Brazil BIANCA MENDONCA REIS1, Gabriela El Bazi1, Ravy Soares Alvares1, Millena Batistela Pereira1, Caroline Borges de Assis1, Bruno Carraro1, Humberto Graner Moreira1 (1) Universidade Evangelica de Goias Introduction: The access to hospital care in Brazil has always been conditioned to each geographic region's socioeconomic discrepancies. Following the isolation resulting of the pandemic of the new coronavirus, the access to health care has been compromised even further, especially regarding treatment for acute myocardial infarction (AMI). Until 2019, AMI represented the leading cause of deaths in Brazil, however, in 2020, with the unfolding of the pandemic, some countries observed a drop in the AMI notifications. Objectives: To describe the reduction in reported cases of AMI among the geographic regions of Brazil. Methods: Observational and descriptive study with a quantitative approach. Data collected using the databases of the Department of Informatics of the Unified Health System (DATASUS) from the Hospital Information System of the SUS (SIH/SUS) and the Mortality Information System (SIM) from January 2017 to December 2020, using the variables: number of hospital admissions; average length of hospitalization; hospital mortality rate and as the underlying cause myocardial infarction, codes I21 to I24 of the 10th International Statistical Classification of Diseases and Related Health Problems (ICD-10). Patients younger than 20 years old were excluded from the study. Results: Comparing data from 2020 to 2019, there was a decrease in cases of AMI in the North, Northeast and Southeast regions, while the South and Midwest presented an increase. In the North region, there was a progressive increase in cases between 2017 and 2018. In 2020, the reduction was of 1.61% cases compared to 2019. In the Northeast region, the reduction of 7.13% cases from 2019 to 2020, was more significant. However, in the Midwest region, there was an increase of 948 cases from 2019 to 2020 while in the Southeast region, there was a decrease of 427 cases. In the South, there was an increase of 3.01% from 2019 to 2020. Conclusion: Despite the expectations of a decrease in AMI cases in all geographic regions the Midwest and South regions presented increasing data. The reduction noticed in other regions is directly related to a sudden drop in the search for AMI treatment due to the imposed social isolation and the fear of contracting a respiratory infection in the hospital environment. Socioeconomic disparities between regions directly interfere with the result. 109915 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Relation of Alcoholic Beverage Ingestion as a Risk Factor for Atrial Fibrillation in Patients with Heart Failure JOAO MARCOS DE FONTES CARNEIRO1, Joao Marcos de Fontes Carneiro1, Daniel Salmito Chaves1, Paulo Roberto Matos Neto1, Felipe Salim Habib Buhamara Alves Nasser Gurjao1, Mateus de Sousa Cavalcante1, Bruna de Almeida Freixedelo1, Benedito Mesley Lima Portela1, Leandro Cordeiro Portela1, David Carneiro Neto1 (1) Universidade Federal do Ceara - campus Sobral Introduction: Sustained alcohol consumption is closely linked to atrial fibrillation (AF), which is the most common heart rhythm disorder. This is due to electrical remodeling in the atrium, which facilitates the formation of arrhythmogenic portions. This condition is of great social relevance, as it is associated with the deterioration of the hemodynamic profile and cardiac output in affected patients, which is, therefore, a worsening factor in heart failure (HF). Objectives: To evaluate the relationship between alcohol intake and the incidence of AF in patients with decompensated HF. Methods: A cross-sectional study was carried out with 322 patients admitted to a cardiology hospital for acute HF decompensation. Information was obtained from a database collected by properly trained health professionals present at the time of hospital admission, with a signed consent form. Participants were divided into two groups: those who had the habit of drinking alcohol and those who did not. Electrocardiographic data were collected in both groups, and the appearance of Atrial Fibrillation was recorded. To verify the significance of the association between alcohol intake and the onset of AF, Fisher's Exact Test was used. The calculation of statistical significance was performed on the OpenEpi platform, using a significance level of p < 0.05. Results: Of the 67 patients with atrial fibrillation at hospital admission, a total of 25 (37.31%) had the habit of drinking alcohol. On the other hand, of the 255 patients who were admitted without atrial fibrillation, only 65 (25.5%) reported drinking alcohol. Thus, there was a significant influence in both groups regarding the consumption of alcoholic beverages as a risk factor for the onset of atrial fibrillation at hospital admission, with a considerable significance level, with p = 0.04062. Conclusion: The habit of drinking alcoholic beverages is an important propensity factor for the development of AF in patients with acute decompensated HF, evidencing the importance of correct control of certain lifestyle habits for the prevention and control of the prevalence of factors that influence the aggravation of the symptoms and greater chance of complications that culminate in a worse prognosis of HF. 111117 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION High Risk for Obstructive Sleep Apnea Syndrome and Diastolic Function on Echocardiography AHYSLA GONCALVES DURAES1, Adson Renato Leite2, Antonio Jose Lagoeiro Jorge2, Cesar Augusto da Silva Nascimento2, Maria Luiza Garcia Rosa2, Wolney de Andrade Martins2, Ana Paula Arriaga Carvalho2, Clara Monica Figueredo de Lima1, Luan Andrade Carvalho3, Emilly Vendramini Mello1, Ana Leticia dos Anjos Sampaio1, Nathalia Felicia Silva Frias1 (1) Universidade Federal do Sul da Bahia (UFSB); (2) Universidade Federal Fluminense (UFF); (3) Universidade Federal do Vale do Sao Francisco (UNIVASF) Obstructive sleep apnea (OSA) is a chronic, progressive disorder with high mortality and morbidity associated with cardiovascular diseases (CVD), including heart failure (HF). OSA-related pathophysiological alterations can directly impact the diastolic function of the left ventricle. Objective: To evaluate the relation between the risk of OSA, considered by the Berlin Questionnaire (BQ), and echocardiogram parameters, related to diastolic function, in individuals without HF assisted by the Family Medical Program of Niteroi (PMF). Methods: Cross-sectional study that included 354 individuals (51% women) aged 45 years or older. The exclusion criteria were the presence of HF, non-completion of the BQ and obese patients with arterial hypertension and not classified as being at risk for OSA by another criterion. All the individuals selected for the study underwent an evaluation, performed in a single day, that consisted of the following procedures: consultation, filling out the BQ and clinical examination, performing laboratory tests and transthoracic doppler echocardiogram (TDE). Results: Of the 354 individuals analyzed, 63% were classified as being at risk for OSA. Patients at risk for OSA present significant alterations in the parameters that assess the diastolic function, which may indicate a worsening of this function in these patients. An adjusted multivariate gamma regression was performed. After adjustment (gender, age, BMI, fasting glucose, triglycerides, serum uric acid, urea albumin/creatinine ratio, systolic and diastolic blood pressure in their continuous forms), risk for OSA confirmed its positive and statistically significant association with indicators of diastolic dysfunction, LAV-i (p = 0.02); E'/A'(p < 0.01), A (p = 0.02), E/A (p < 0.01). Conclusion: Our data show that patients at risk for OSA present a worsening in the diastolic function parameters measured by the TDE. 109931 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Heart Failure Morbidity and Mortality Profile in Brazil in the Last 5 Years GABRIEL COELHO BRITO DIAS1, Mariana Salles Ballalai1, Jose Levi Tavares Cavalcante1, Helena Raquel Nogueira de Oliveira1, Isabela Aragao Colares1, Gabriel Sousa Santos1, Renata Pinheiro Martins de Melo1, Ane Karoline Medina Neri2, Weiber Silva Xavier3, Joao Luiz de Alencar Araripe Falcao1, Sandra Nivea dos Reis Saraiva Falcao1 (1) Universidade Federal do Ceara (UFC); (2) Hospital Universitario Walter Cantidio (HUWC); (3) Programa de Educacao em Reanimacao Cardiorrespiratoria (PERC) Introduction: Heart Failure (HF) is a syndrome in which the heart is unable to adequately pump blood to meet organic needs. Despite clinical advances, HF is the leading cause of hospitalization among circulatory system diseases. Objectives: To describe the morbidity of HF in Brazil and its impact on public health in the country. Methods: Observational descriptive study conducted using data obtained from DATASUS. The variables gender, age group, death and hospitalization costs of patients with HF between 2017 and 2021 were analyzed. Results: In the period, the total number of hospitalizations was 928,541, with the highest number occurring in 2017 recording 209,162 (22.53%) and decreasing annually until the lowest value in 2021 (16.27%). There was a predominance of male patients representing 480,691 (51.77%). The most affected age group was the elderly aged 70 to 79 years with 26.40% of hospitalizations. In addition, 108,692 deaths were registered in the period, totaling 11.71% mortality rate for HF within this time frame. Finally, the average amount spent per hospitalization was R$ 1,649.47. Conclusion: We analyzed the numbers of hospitalization and deaths due to HF in the last five years and we found that HF is still very prevalent in Brazil and, in despite of the decrease in the mean number of hospitalizations in 2021, it is an important cause of death in the country and a significant source of state expenses. Furthermore, we noticed that the hospitalized patients tended to be male and aged 70 to 79 years. Thus, a greater strict prevention in populations at risk is necessary and the importance of early recognition associated with an adequate treatment strategy is reaffirmed. 109933 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Ami Mortality During the First Year of the COVID-19 Pandemic: Lifestyle Improvements or Distraction? RAVY SOARES ALVARES1, Gabriela El Bazi1, Bianca Mendonca Reis1, Millena Batistela Pereira1, Caroline Borges de Assis1, Bruno Carraro1, Humberto Graner Moreira1 (1) Universidade Evangelica de Goias Introduction: The search for medical assistance during the coronavirus pandemic in Brazil has declined significantly. Furthermore, the fear of contracting covid in hospitals and the prioritization of urgency and emergency care over elective consultations resulted in a decrease in the search for medical assistance during the pandemic. Faced with this new reality, some changes were noticed in the country's morbidity and mortality rates, since the Acute Myocardial Infarction (AMI), the leading cause of death in the country until 2019, presented significant decrease during the pandemic. Objectives: To describe the incidence of AMI by sex and age group during the pandemic. Methods: Observational and descriptive study with a quantitative approach. Data was collected using the databases of the Department of Informatics of the Unified Health System (DATASUS) from the Hospital Information System of the SUS (SIH/SUS) and the Mortality Information System (SIM) from January 2017 to December 2020, using the variables: number of hospital admissions; average length of hospitalization; hospital mortality rate and as the underlying cause myocardial infarction and then stratified by age group, and sex, encompassing only individuals over 20 years old. Results: In 2020, the age group with the highest hospitalization rate for AMI was the one of 60 to 69 years old, while the lowest rate belongs to the age group of 80 years and older. In the age group of 80 years and older, females had the most significant reduction (3.3%) in hospitalizations while males decreased in 1.5% Previously to the pandemic, there was an annual progressive increase in mortality by AMI, however in 2020 there was an overall reduction of 6118 deaths when compared to 2019, being that the age group of 80 years and older presented a decrease of 56.15% of total deaths. Females presented a reduction of 2886 deaths in 2020 when compared to 2019 while males, in the age group of 80 years and older, presented a reduction of 30.9% of cases Conclusion: A reduction in hospitalizations and mortality by AMI was expected and confirmed in this study. However, it could be noticed that the main reason behind said reduction was not the improvement in people's lifestyles and subsequent reduction in cardiovascular diseases, but the association between the lower search for hospital assistance and the fact that the AMI symptoms can be disguised by the coronavirus infection due to the latest's greater expressiveness. 111850 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOGERIATRICS Low Aerobic Capacity as a Predictive Factor for Ventricular Dysfunction in Elderly Undergoing Stress Echocardiography ALLEXA GABRIELE TEIXEIRA FEITOSA1, Gabriela de Oliveira Salazar1, Jose Icaro Nunes Cruz1, Claudia Bispo Martins-Santos1, Lara Teles Alencar Duarte1, Cleovaldo Ribeiro Ferreira-Junior1, Edvaldo Victor Gois Oliveira1, Andre Pinheiro Zylberman1, Eduardo Jose Pereira Ferreira1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe - UFS Introduction: The advance of age is an important risk factor for cardiovascular diseases, including ventricular dysfunction, which makes the elderly an important research and control group. Objective: To identify predictors of ventricular dysfunction in a population of elderly people and to evaluate the level of aerobic capacity of these patients. Methods: Cross-sectional study between January 2000 and January 2022 with individuals over the age of 60 years undergoing Physical Stress Echocardiography (SE) in a respected cardiological service. 1644 (68 +- 6 years) patients were categorized according to cardiorespiratory capacity (CRC) into low (MET < 7,9), intermediate (7,9 <= MET < 10,9) and high (MET >= 10,9) fitness. The chi-square test and logistic regression were used using SPSS Statistics software version 22.0. A significance level of 5% was admitted. Results: Among the patients analyzed, 40,8% had low CRC, 34,8% intermediate and 24,4% had high aerobic capacity. Of the total, 8,2% (135) had ventricular dysfunction. Low CRC was associated with the presence of: systemic arterial hypertension, sedentary lifestyle, obesity, alcohol consumption, female sex (p < 0,001) and family history (p = 0,01). Male sex (OR = 1,950; IC95% = 1,328-2,863; p = 0,001), diabetes mellitus (OR = 1,908; IC95% = 1,267-2,874; p = 0,002), smoking (OR = 2,540; IC95% = 1,409-4,577; p = 0,002), dyslipidemia (OR = 1,588; IC95% = 1,092-2,307; p = 0,015), low CCR (OR = 3,218; IC95% = 1,846-5,611; p < 0,001) and intermediate CCR (OR = 1,989; IC95%1,129-3,503; p = 0,017) were predictors of ventricular dysfunction in the elderly. Conclusions: Low aerobic capacity was associated with systemic arterial hypertension, sedentary lifestyle, obesity, alcohol consumption and the female sex, as well as being a predictor of ventricular dysfunction in the elderly. 110112 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Association between Arterial Stiffness Through Aortic Pulse Wave Velocity and Increased Heart Disease in Copd Patients BIANCA VASCONCELOS BRAGA CAVALCANTE1, Ana Livia Gadelha Xavier da Nobrega Pereira1, Beatriz Gadelha e Xavier1, Leticia Lacerda Burity1, Rayanne Alessandra da Silva Barreto1, Vinicius Vieira Leandro da Silva1 (1) FACULDADE DE MEDICINA NOVA ESPERANCA - FAMENE Introduction: Chronic obstructive pulmonary disease is one of the main causes of mortality in the world and is closely related to cardiovascular diseases, with a risk of 4.5 times greater compared to the healthy population. There is a correlation between heart failure (HF) and COPD, which has been extensively investigated in recent years. Objective: To correlate arterial stiffness in patients diagnosed with COPD. Method and materials: This is a systematic review of the literature indexed between 2018 and 2022, published in the Scientific Electronic Library and PubMed databases. The following terms were applied to the Health Science Descriptors (DeCS): "Chronic Obstructive Pulmonary Disease" and "Aortic diseases". Articles unrelated to the topic and inaccessible for free were excluded. Results: It is known that about 30% of patients with HF are also diagnosed with COPD, which corroborates the prognosis of increased hospitalizations and mortality in these people. There are few studies that report which biomarkers are related to the two diseases, but it has been seen that aortic pulse wave velocity (aPWV) is the gold standard measure to determine arterial stiffness and, therefore, is a predictor for elevated cardiovascular events. in COPD patients (defined as +0.7 m/s). In a meta-analysis, a +1 m/s increase in aPWV was reported to determine a 15% increase in the risk of heart disease. A plausible explanation for the relationship between aPWV and COPD is the pathological mechanism of degradation of elastin fibers in the lungs and large arteries, such as the aorta, since patients with COPD lose a large part of the cutaneous elastin, which generates severity in emphysema. and arterial stiffness. Conclusion: It is known that these data can influence the determination of the negative impacts of the two pathologies. Thus, there is a clear need for further studies on biomarkers related to COPD and heart disease. 111395 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Deaths Caused by Acute Myocardial Infarction in a State of the Brazilian Amazon from 2016 to 2020 AMANDA GABRIELA FREITAS RODRIGUES1, Matheus Ricardo Malveira Camacho2, Lucas dos Santos Fontes1 (1) Universidade Federal do Para; (2) Universidade Estadual do Para Introduction and/or Fundamentals: Acute myocardial infarction (AMI) is responsible for significant mortality rates in Brazil and worldwide. Despite the implementation of national policies to prevent precursor diseases of cardiovascular importance such as hypertension and diabetes, mortality rates from AMI remain high compared to the rates of developed countries. Therefore, the analysis of the epidemiological profile of deaths caused by AMI in Brazil is crucial, so that the strategy towards reducing mortality from this disease is more accurate. 2. Objectives: Trace an epidemiological profile of deaths caused by acute myocardial infarction in the state of Para, Brazil, from 2016 to 2020. 3. Methods: Analysis of data provided by the digital platform of the Department of Informatics of the Unified Health System (DATASUS), in the category "deaths from preventable causes from 5 to 74 years old", ICD-10 category "I21 Acute myocardial infarction", selecting the sections according to the search parameters, such as "sex" and "education". 4. Results: In the period evaluated, there was a trend of growth in the number of cases of deaths caused by AMI; 1577 were registered in 2016; 1709, in 2017; 1721, in 2018; 1840, in 2019; and 1863, in 2020; totaling 8710 deaths. There was a greater involvement of men (n = 5953/68.4%) and less of women (n = 2757/31.6%). Regarding self-declaration of color, most deaths were registered in brown people (n = 6702/76.9%), followed by white (n = 1181/13.5%) and black (n = 605/6.9%). People aged between 60 and 69 years were more affected (n = 3343/38.4%), followed by people aged between 50 and 59 years (n = 2159/24.8%) and people aged between 70 and 74 years old (n = 1697/19.5%). In addition, in relation to schooling, there was a higher occurrence among people with 4 to 7 years of schooling (n = 2193/25.2%), followed by people with 1 to 3 years of schooling (n = 2138/24.5%) and people with 8 to 11 years of schooling (n = 1614/18.5%). 5. Conclusion: This study has found an important social stratum in the data in question; people with up to 7 years of schooling symbolize 49.7% of the total number of cases registered and analyzed, indicating an influence of social status in this scenario, as well a stronger the prevalence of AIM between males. Therefore, public policy should be more aware of epidemiological data to define strategies to prevent AIM. 109957 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Disorders Caused by Hellp Syndrome in Women During Gestational and Post Childbirth Period: A Systematic Review RAFAEL AUGUSTO SILVA CABECA1, Ingrid Jade Muniz Wanderley1, Joao Lucas Silva Sales1, Israel Figueira Lemos1, Ivan Cuoco Sampaio1, Maria Eduarda Dantas da Veiga1, Mariana Lassance Maya Palheta1, Juliana de Sousa Tavares1, Luiz Carlos Figueiredo Filho1, Luma Maria Favacho Bordalo1, Paula Larissa Baia Lima1 (1) Universidade do Estado do Para Background: HELLP Syndrome (hemolysis, elevated liver enzymes and low platelets) is a multisystemic disorder that usually arises from a serious condition of pre-eclampsia, which is present in 7,1% of pregnant women with hypertensive disorder. The presence of this condition is responsible for the development of endovascular endothelial damage by the intravascular platelet activation, which leads to many cases of maternal, perinatal and neonatal morbidity and morbimortality. Objective: Describe, through a systematic review, the available evidence about the maternal disorders arising from HELLP syndrome. Methods: A systematic review with articles collected at MEDLINE, Scielo and LILACS databases published from 2017 to 2022, using the descriptors "HELLP" and "HELLP Syndrome". Were included cohort retrospective studies, full text available, in english, spanish and portuguese languages, while studies with tematic deviation, duplicated and articles that haven't published results. This review was based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) standards and procedures. Results: 310 articles were collected, and after the selection, analysis and the application of exclusion and inclusion criteria, 11 articles were selected. In the period of study, the analysis of publications demonstrated the prevalence of three poor outcomes on pregnant women's clinical conditions: liver damage, kidney damage and hypertension, which were classified as primary outcomes. Furthermore, the studies described the following secondary outcomes: premature birth, placental abruption and pulmonary infection, uterine infection and gastrointestinal infection. Were observed the presence of gestational diabetes and congenital abnormalities caused by placental disorders. In addition, cerebrovascular morbidities were detected in patients with HELLP syndrome, and epigastric pain was the main isolated symptom on pregnant women, despite some patients related to having both symptoms in considerable part of the cases. The outcomes associated with cardiac disorders were concentric hypertrophy of the left ventricle and diastolic dysfunction. Conclusion: In this aspect, although HELLP syndrome is a rare obstetric condition, it was possible to observe that the outcomes resulted by, particularly related to hepatic, kidney and vascular damages, may leave after-effects at short and long term in the life of the pregnant. 109965 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Temporal Analysis of the Mortality Rate and Epidemiological Profile of Patients who Died from Atherosclerotic Disease in Brazil between 2012 and 2021 BRUNO OLIVEIRA SOUZA PRATES1, Hildebrando Antunes de Carvalho Neto1, Beatriz Souza Martins1, Beatriz Catarina dos Santos de Oliveira1, Gabriela Chateaubriand Campos1 (1) Universidade Federal da Bahia - UFBA Introduction: Atherosclerosis is a chronic inflammatory disease of multifactorial origin and is one of the main causes of morbidity and mortality worldwide. Its prevalence has been increasing rapidly in developing countries, such as Brazil, and this growth is closely linked to the lifestyle adopted by the population. In this way, the epidemiological study of deaths associated with atherosclerosis is presented as a tool to assess the efficiency of the treatment instituted. Objective: To analyze the epidemiological profile of patients who died from atherosclerotic disease in Brazil, between 2012 and 2021. Methods: This is an ecological time series study from secondary data collected by the Hospital Information System (SIH-SUS), between the years 2012 to 2021. The total and percentage distribution of deaths, the mortality rate and sociodemographic data were included. Results: A total of 7.927 deaths were recorded during the analyzed period, with 2012 presenting 572 cases and 2021 with 1.006. The mortality rate presented an oscillatory character, varying in a range between 3.63 (in 2017) and 4.11 (in 2021). There was no significant difference between genders, but the age group most affected was the elderly over 60 years (89.29%). Furthermore, the Southeast region has the highest number of cases with 3,967 (50.04%) followed by the Northeast region with 2,169 (27.36%). Conclusions: As can be seen from the data obtained, despite the fact that the main risk factors for the development of atherosclerosis, as well as their treatment, are currently very well established, the numbers of deaths continue to increase in Brazil. And this increase is not just due to population growth, since the highest mortality rate in the historical series was recorded in 2021. As for sociodemographic data, the need for greater attention to elderly patients was once again reinforced, since they account for almost 90% of deaths. Finally, the data obtained prove that atherosclerosis remains an important and preventable cause of death in Brazil. 109968 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM SARS-COV-2 Pandemic and Mass Vaccination: Impact on Morbidity and Mortality from Acute Myocardial Infarction in the Brazilian Southeast CAMILLA MATTIA CALIXTO1, Alice Magro Koscianski1, Ana Carla Dlugosz1, Bruna Karas1, Francielle Nocera Viechineski1, Julia Henneberg Hessman1, Larissa Almeida Busnello1, Paola Goncalves Moreira de Oliveira1, Mario Claudio Soares Sturzeneker1 (1) Universidade Estadual de Ponta Grossa (UEPG) Introduction: Acute myocardial infarction (MI) is the primary global cause of death, and accounted for 7.06% of all deaths in Brazil in 2017. Chest pain is the cause of up to 40% of hospital admissions; and 10% of non-traumatic visits to the emergency department. The pandemic could reduce access to healthcare due to hospital overcrowding and the reduced seeking of the healthcare system, although the evidence is limited. Objective: Estimating the possible influence of the SARS-CoV-2 pandemic on morbimortality related to acute MI in the Southeast region through analysis of DATASUS data from 2017 to 2021. Methods: Data on the number of admissions, mortality, lethality, and duration of inpatient stay was collected. The lethality was calculated as the ratio of deaths over admissions and expressed as a percentage. We studied the periods pre-pandemic (02/2017 to 02/2020), pandemic (03/2020 to 06/2021), pandemic's peak (12/2020 to 05/2021), peak's 1st trimester (12/2020 a 01/2021), peak's 2nd trimester (03/2021 a 06/2021), and mass vaccination (06/2021 a 12/2021). We calculated the mean of each variable for sex and age group. We compared the mass vaccination period to the others and recorded the difference between means as a percentage. Results: During mass vaccination, there was an increase of 6.69% in admissions compared to the pre-pandemic period, 10.35% compared to the peak, and 20.4% for the 2nd trimester, particularly among women (5.87%, 12.03%, and 23.06% respectively). The duration of stay dropped by 15.34% compared to the pre-pandemic period in a similar way between the sexes. Regarding the pandemic's peak, the 2nd trimester showed a 4.66% increase. The mortality increased, especially comparing the peak's 2nd trimester with the vaccination period (18.66%). The lethality showed mixed results with a slight upward tendency. There was a 9.44% increase compared to the 1st trimester and a 1.46% drop for the 2nd trimester. The sex and age analysis had similar results, except for an increase in all comparisons in the age group 40-49 and a reduction in the 30-39 age group. Conclusion: After the mass vaccination period, there was an increase in mortality and hospital admissions. The duration of inpatient stay decreased compared to the rates before the pandemic and increased compared to the pandemic's peak. The lethality had a slight upward tendency. 110011 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Results of the Surgical Treatment of the Mitral Valve by a Minimally Invasive Procedure in Rheumatic and Degenerative Disease, Comparison of Results SHEMA EL-LADEN HAMMOUD1, Juliana Fortunato2, Jeronimo Antonio Fortunato Junior2, Leticia Gusso Scremin1, Nikolai Cernesco Neto1, Gabriel Fontana de Melo1, Brenda Gabriele Smaniotto Raulik1 (1) Universidade Positivo; (2) Hospital Cruz Vermelha Brasileira - Filial do Parana Introduction: In Brazil, valvulopathies represents a significant portion of hospitalizations by cardiovascular disease. Rheumatic Fever is the main etiology, representing 70% of all cases, unlike developed nations, where degenerative diseases (DD) are the main cause. For patients that have DD, mitral valvuloplasty with a ballon catheter (MVBC) is still the most recommended treatment. However, in the last decades the minimally invasive cardiologic surgery (MICS) assisted by video, recieved a major boost and has become a possible choice of treatment to the diseases of the mitral valve. In pacients with a rheumatic disease (RD), the inicial treatment is farmacologic, reserving the surgical intervention on refratary cases. Objective: To compare the results of mitral valvuloplasty performed using the MICS techinique in patients with DD and RD; and also assess the initial surgical results with a five year evolution from the same patients. Methods: Between 2005 and 2019, patientes with Degenerative Desease (43) and Rheumatic Desease (36) undergoing MICS were selected totalizing 79 patients. Results: Among the patients selected, 56% were female and the average age was 49 years. Of all valve alterations, the rheumatic etiology prevailed in mitral valve stenosis while the degenerative disease prevailed in mitral valve insufficiency. There were 97,7% of plasties in DD, against 72,2% in RD. Sequential echocardiography showed minimal mitral regurgitation in 88,4% in patients with DD, versus 61,5% in RD. Left ventricular diastolic dimension was 57,8 mm in DD pacients, versus 51 mm in RD. Valve replacement after plasty failure occurred in the initial postoperative period from one pacient with RD and another pacient with DD, one year later the procedure. Five years later, one pacient with DD was submitted to a new surgical procedure due to mitral endocarditis. Late survival after 10 years of follow-up was 91,67% in RD versus 88,4% in DD. Conclusion: As observed in the world literature, the surgical results in pacients with DD was satisfactory. In pacients with RD the surgical results were also promising, with increased survival. 110013 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Assessment of Discordances and Causes of Pathological Q Wave Discordance, using the Minnesota Code, in Patients from the Longitudinal Study of Adult Health (Elsa-Brasil) GABRIEL FELIPE GONZAGA SILVEIRA1, Antonio Luiz Pinho Ribeiro1, Marcelo Martins Pinto-Filho1 (1) Universidade Federal de Minas Gerais UFMG; (2) Universidade Federal de Minas Gerais UFMG; (3) Universidade Federal de Minas Gerais UFMG The electrocardiogram (ECG) is a simple and useful clinical tool, used in population studies as a tool for disease prognosis estimation. The Minnesota code (CM) is used for better standardization of the ecg reading. The degree of ECG variability in the same patient (as well as the variation of codes) over time is not well established, with some reporting significant variations including pathological Q waves. The aim of the present study is to evaluate the discordance and causes of these discordances in major Q-wave CM in patients from The Longitudinal Study of Adult Health (ELSA-Brasil) over a 4-year follow-up period. The ELSA-Brasil is a multicenter cohort that included more than 15,000 participants aged between 35 and 74 years at baseline. The ECG is one of the tests performed in the study. For the present study, the presence of pathological Q wave was evaluated in a total of 26,516 ECGs performed in the years 2013 (13,877) and 2018 (12,639), using the major criteria of group 1 of the Minnesota Code (CM 1.1 a 1.2). The ECGs were performed in a sequence called waves 1, 2 and 3. The ECGs of wave 3 were fully lauded and coded with manual review and therefore were considered the gold standard for comparison. Waves 2 and 3 ECGs were compared in order to observe the discordance and causes of these discordances in the larger Q wave CM. We called Major Disagreement when there were changes in the pathological Q wave category, that is, the major Q wave pathological changes changed to minor or non-existent pathological changes between the groups in the CM. Minor disagreement: when there are changes in the CM, but no change in the Q wave category. Total agreement when the CM is identical and New pathological Q wave: when new pathological Q wave events have occurred. Patients without ECG were excluded. From the 26,516 electrocardiograms performed, we found 1,562 major changes in the Q wave (CM 1.1 and 2.1). When comparing the electrocardiograms performed in 2013 (13,877) and 2018 (12,639) we found 121 (1.0%) total agreement. Minor disagreement: 94 (0,7%). Major disagreement: 5 (0.04%) and New pathological Q wave:713 (5.6%). In conclusion, there was little Total agreement between the 2013 and 2018 ECGs. Most of the disagreements are due to Minor disagreement, which is possibly due to millimeter variations in measurement and the New pathological Q wave, which possibly occurred due to the aging of the population of the study. 110032 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Impacts of the Pandemic on the Increase in Mortality from Heart Failure in a Developing Country SOFIA HELENA VITTE1, Idrys Henrique Leite Guedes2, Joanna Sousa da Fonseca Santana3, Marclebia Quesado Borges4, Marcelle Rodrigues Carneiro de Souza Reis5 (1) Pontificia Universidade Catolica de Campinas; (2) Universidade Federal de Campina Grande; (3) Escola Bahiana de Medicina e Saude Publica; (4) Universidade Federal do Reconcavo da Bahia; (5) Centro Universitario do Planalto Central Apparecido dos Santos Introduction: Congestive heart failure is a complex syndrome that is a result of either functional or structural disorder, which can be divided into caused by heart failure such as ischemic heart disease and systemic hypertension. During the pandemic, it was possible to see a scenario that got worse in a country that faced serious consequences due to the coronavirus onset, with higher mortality data. Thus, our main goal was to show this impact on the statics of heart failure in an emergent country. Methodology: A cross-sectional quantitative study was carried out using the open database of the Brazilian Ministry of Health (DATASUS). Information on hospitalizations and mortality rates for heart failure, as well as hospitalizations for ischemic diseases and primary hypertension from January 2018 to December 2021, were analyzed. Results: There were 201,040 and 199,858 hospitalizations for heart failure in Brazil in 2018 and 2019, respectively, while in 2020 and 2021 these values were 167,375 and 151,106, which represents a reduction of 20.5% between the averages of the two biennia. In these same periods, heart failure mortality rates ranged from 11.12 and 11.41 in 2018-2019 to 12.11 and 13.54 in 2020-2021, resulting in a 13.8% increase between the two periods. Finally, average hospitalizations for other ischemic diseases and primary hypertension in Brazil decreased by 23.7% and 30.7% in 2020-2021 compared to 2018-2019. Conclusion: From the available data, a significant reduction in the number of hospitalizations for heart failure after the beginning of the pandemic, as well as for hypertension and ischemia, can be observed. Conversely, the mortality rate for the pathology grew, which demonstrates a possible relationship between the limitations imposed in the period on the adequate treatment of the two main etiologies of heart failure in the country. 110945 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Prevalence of Orthostatic Hypotension in the Municipality of Serta CATARINA RAQUEL GASPAR DOS SANTOS1, Patricia Coelho1, Francisco Rodrigues1 (1) Instituto Politecnico de Castelo Branco Introduction: It is characterized as Orthostatic Hypotension when there is a drop in systolic blood pressure greater than 20 mmHg and/or 10 mmHg in diastolic blood pressure. Its symptoms are related to cerebral hypoperfusion, such as blurred vision, nausea, palpitations, headache, neurological changes, and loss of balance. Its prevalence is associated with increasing age. Objective: To determine the prevalence of orthostatic hypotension in the population of Serta. Methodology: Prospective study with sample collection based on the cluster method, through the random selection of streets in the municipality of Serta. Initially, anthropometric data were collected and, as a base, an assessment of blood pressure was carried out with the individual sitting and at rest, then, with an interval of 3 minutes, after this medication, blood pressure was reassessed in the sitting position. orthostatic. Statistical treatment and data analysis were performed using the SPSS Statistics program. Results: The sample is composed of 1000 individuals, of legal age and residing in the municipality, 515 (52%) male and 485 (48%) female. The mean age was 56.04 years with a standard deviation of +-16.04 years. It was found that 7.4% of the sample has orthostatic hypotension, with 54.1% being male and 45.9% female. Regarding the age groups, it was between 61 and 70 years old that stood out the most with this diagnosis, with a represented value of 41.9%. Discussion: Like the results found in the present study, there is an article on the study of Orthostatic Hypotension in the municipality of Proenca-a-Nova, in which a prevalence of 5.3% of the population with this diagnosis was found, having been more prevalent in females, contrary to what was observed in the municipality of Serta. Conclusions: Despite the low prevalence, it is still important to carry out its diagnosis in health units since this risk factor is also associated with cardiovascular disease. 110072 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Jugular Venous Ultrasound for the Diagnosis of Heart Failure in the Emergency Department - a Systematic Review MAYARA GABRIELE TOLEDO1, Caio Pluvier Duarte Costa1, Eduardo Thadeu de Oliveira Correia1 (1) Universidade Federal Fluminense Introduction: Tools that aid the differentiation of dyspnea from cardiovascular and noncardiovascular etiology are fundamental in the emergency department (ED). In this study we will systematically review if internal jugular vein (IJV) ultrasound can serve as a screening method for the diagnosis of heart failure in the ED. Methods: We conducted a systematic review following the PRISMA guidelines. Original studies indexed by Embase, Pubmed, Cochrane and LiLACS with the keywords: "ultrasound" or "ultrasonography" and "heart failure" and "jugular vein" published until March, 2022 and which matched the inclusion criteria were included. Two authors (C.P and M.T.) performed the screening and data extraction, in cases of discordance, a third author (E.T.) made the decision. Results: Eight studies were included, with a total of 931 patients analyzed. The ultrasound examination of the IJV was used to evaluate patients with dyspnea in ED, using different methods. Due to significant heterogeneity between studies, a meta-analysis was not performed. All of the included studies showed that IJV ultrasound had a high sensitivity for differentiation of dyspnea on the ED. Jang et al defined 10 cmH2O of central venous pressure (CVP) as a good cutoff to define HF by IJV ultrasound for patients without jugular vein distension on physical examination, showing a sensitivity of 98.2% and a specificity of 42.9% for IJV ultrasound in dyspneic patients comparing with pulmonary edema on initial Chest x-ray, a sensitivity of 99%, specificity of 59% compared with echocardiography, and finally a sensitivity of 100%, specificity of 43% compared with a BNP >= 500 pg/ml. Tzadok's study evaluated the use of the change of the IJV area with respiration in patients with dyspnea to detect acute HF, showing that the respiratory area change of the IJV had a specificity and sensitivity of nearly 70% rate to identify HF. Conclusion: Our systematic review demonstrates that IJV ultrasound is a complementary tool that provides important information for the diagnosis of HF in patients with dyspnea in the ED. Further studies are needed to define a standard measurement method to apply IJV ultrasound in clinical practice. 110064 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Cardio Oncology Applied to a Ecological Study in a Emergent Country SOFIA HELENA VITTE1, Idrys Henrique Leite Guedes2, Joanna Sousa da Fonseca Santana3, Marclebia Quesado Borges4, Marcelle Rodrigues Carneiro de Souza Reis5, Allan Christian Cardozo Cembrane6 (1) Pontificia Universidade Catolica de Campinas; (2) Universidade Federal de Campina Grande; (3) Escola Bahiana de Medicina e Saude Publica; (4) Universidade Federal do Reconcavo da Bahia; (5) Centro Universitario do Planalto Central Apparecido dos Santos; (6) Hospital Alvorada Brasilia Cardio-oncology is a field focused on detection, monitoring and treatment of cardiovascular disease occuring due to chemotherapy cardiotoxicity. Not only that, but cardiovascular diseases and cancer share multiple risk factors, such as increased age, smoking and obesity, and the presence of one condition worsens the other. Even though cardio-oncology is a new field, the most researched topics are focused on chemotherapy' toxicity and cardiac assessment during treatment, leaving very little room to discuss heart malignancies. 25% of malignant cardiac tumors are cardiac sarcoma, and secondary tumors are 40 times more likely to appear. Therefore, the aim of this study is to analyze the profile of heart, mediastinum and pleural cancer in Brazil. This is a cross-sectional descriptive population based study with values obtained from the database of the Ministry of Health of Brazil (DATASUS) during the period from 2018 to 2021. The analyzed variables were: treatment time, sex, year and age group. The tables were obtained and exported to the IBM SPSS 26 statistical software for the purpose of comparing the variables. A total of 4438 diagnoses were accounted, with 2143 corresponding to males and 2295 to females. In the annual distribution, we can observe an increase of approximately 93.6% from 2018 to 2019, and a decrease of 12% from 2019 to 2020 and of 16.5% from 2020 to 2021. The most affected age group was from 60 to 69 years old. Finally, regarding the average treatment time, it can be observed that in 2,020 cases, treatments lasted up to 30 days, while 71 cases were between 31 and 60 days and 123 cases were for more than 60 days. Data shows a decrease in the number of diagnosed neoplasms in Brazil in the post-pandemic period, with a small increase between 2020 and 2021. Among those affected, elderly people, under 70 years old, are the age group with greater expression of the disease. However, it is not possible to establish a relationship between sexes, due to the small difference in cases. Regarding the treatment, most of it was done within a period of up to 30 days, showing a small time rate of tratament. 110065 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Comparative Cross-Sectional Study of the Incidence of Chagas Disease with Deforestation in the Amazon Region of the State of Para MARCIO CESAR RIBEIRO MARVAO1, Giovanna Coutinho Jardim2 (1) Instituto Evandro Chagas (IEC); (2) Universidade Federal do Para (UFPA) Introduction: Chagas disease is an anthropozoonosis caused by the parasite Trypanosoma cruzi that is considered a public health issue in several countries of The Americas, being endemic in 21 countries of the continent, reaching about 7 million people. There are several pathophysiological mechanisms that surround Chagas disease, so that there is permanent tissue repercussion, autosomal abnormality and impaired coronary microcirculation, the latter can generate decreased myocardial performance and impair the functional capacity of the affected person. The relationship between Chagas and deforestation can be addressed by the theme of destruction of the vector habitat, causing its migration to areas with human presence. The state of Para, northern Brazil, leads deforestation rates in the Amazon region, in addition to suffering from chagas disease endemics. Objective: To perform a comparative analysis between deforestation data and incidence of acute chagas disease in the state of Para from 2015 to 2020. Methodology: Cross-sectional, observational and descriptive study, with data from the Notifiable Diseases Information System (SINAN/DATASUS) on the frequency of acute chagas disease in the state of Para. The linear regression test was used using the PASR4.03 software to verify the statistical relationship. The variables of annual forest loss, forest cover rate and forest deforestation rate were analyzed. Results: During the period described, the highest incidence occurred in 2016, marking 3.3 new cases per 100,000 inhabitants. In relation to the forest situation, the greatest loss of forest cover (hectare) marked the year 2020, representing a loss of 675591.3, with a forest deforestation rate of 24.93%, followed by 2016, with 597199 of area loss and with a rate of 24.04%. The statistical correlation showed R2 = 37% of events, demonstrating a variability of 63% of the relationship occurring by other factors. Non-significant P-value (0.19997). Conclusion: Although deforestation is a major problem for the onset of diseases and a decrease in the quality of life of the population. The data collected did not bring a significant relationship between deforestation and the incidence of chagas in the described region, not ruling out this relationship in other locations. 111668 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Profile of Patients who Died from Aortic Valve Stenosis (AVS) in Brazil in the Last 10 Years VALENTINA BRATTI DE NADAL1, Pedro Van Der Sand Germani2, Juliana Nichterwitz Scherer1 (1) Universidade do Vale do Rio dos Sinos (UNISINOS); (2) Pontificia Universidade Catolica do Rio Grande do Sul Introduction: AVS is, in children and adults, the most common cause of left ventricular outflow obstruction. When the severity of Aortic Valve Stenosis is low to moderate, the disease is well tolerated and is usually not accompanied by symptoms. When it progresses to severe, AVS is associated with significant mortality. The classic manifestations when the disease is in terminal stage are dyspnea on exertion, syncope and angina. It is important to identify the profile of patients who died from such condition in order to provide more adequate screening and to identify risky groups. Objective: To describe the profile of patients who died from AVS in Brazil in the last 10 years. Methodology: An ecological study was conducted through the collection and analysis of data from the Departamento de Analise de Saude e Vigilancia de Doencas Nao Transmissiveis (DASNT) system, covering the period from January 2011 to December 2021. The variables evaluated were: number of deaths for AVS, geographic region and place of occurrence, age group, race/color and sex. All data were extracted into an excel spreadsheet, and the descriptions of the variables were performed by analyzing absolute and relative frequencies. Results: A total of 32,094 deaths due to AVS were recorded in Brazil between 2011 and 2021. Of these, 53.6% were females and 46.3% were males. Considering age group, 96.1% of deaths occurred in individuals over 50 years old, with 47.3% of total deaths being aged 80 years old or over. The lowest rate occurred in patients aged 05 to 09 years, totalizing 0.06%. About race/color, 73.8% of deaths occurred in white patients, 17.8% in brown and 3.5% in black, while the lowest rate occurred in indigenous people, 0.09%. Regarding region, the Southeast had the highest rate of deaths (50.9%), followed by the South (26.3%) and the Northeast (14.7%). The North and Midwest accounted for 8.1% of deaths. Conclusions: As 96.1% of deaths caused by AVS occurred in patients over 50 years old, it should be noted that there is a need for medical management to identify these patients before they become symptomatic, which improves survival. Public policies that propose regular monitoring of these patients are extremely important to monitor hemodynamic progression and the development, mainly in the Southeast, where there were 50.9%% of deaths. 110074 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Golden Ratio Deviation: SBP/DBP and DBP/PP Coefficients During Ambulatory Blood Pressure Monitoring in Diabetics and Resistant Hypertensive Patients LOUISE BUONALUMI TACITO YUGAR1, Larissa Costa Morete2, Tatiana Rubio Azevedo2, Elizabeth do Espirito Santo Cestario2, Bruno Rodrigues1, Silvia Elaine Ferreira Souza Melo1, Carolina Manzano2, Lucia Helena Bonalume Tacito2, Jose Fernando Vilela Martin2, Heitor Moreno Junior1, Juan Carlos Yugar Toledo2 (1) Faculdade de Ciencias Medicas, UNICAMP; (2) Faculdade de Medicina de Sao Jose do Rio Preto, FAMERP Introduction: The wave pressure profile can be separated into three segments: pulse pressure (PP), diastolic blood pressure (DBP) and systolic blood pressure (SBP), which corresponds to the sum of the previous ones. Although the measurement of these values has advanced, there are still few studies on the relationship between them. The golden ratio (ph, phi, or Fibonacci number) is present in several organisms and is defined by dividing a straight line into two segments a and b (a being greater than b) so that the ratio between a and b is equal to the ratio of the sum of the quantities by the larger segment. The value of this equality is approximately 1.61. In this sense, we try to relate SBP, DBP and PP to phi. In this study, we evaluated and compared the deviations from the golden ratio during the periods of ABPM: 24h, daytime and nighttime in resistant hypertensives (RHTN) and type 2 diabetics (T2DM) using the SBP/DBP and DBP/PP ratios for comparison. Material and Methods: We retrospectively analyzed data from RHTN participants (n = 54) from the ResHypOT ClinicalTrials.gov study, ID: NCT 02832973 and T2DM patients (n = 81) from the study "Changes in vascular hemodynamics in patients with RHTN and T2DM. The data used were: age, sex, SBP, DBP and PP. Descriptive statistical analysis, t-test and ANOVA were performed with SPSS 24 softwares (IBM-USA). Results: We observed elevated blood pressure values in RHTN and normal values in T2DM in the 24-hour periods, daytime and nighttime with attenuation of the systolic and diastolic nocturnal dipping, being more pronounced in the RHTN group. The SBP/DPB ratio in the 24-hour period and nighttime was significantly higher in the T2DM group when compared to the RHTN group (p = 0.0063 and p = 0.044, respectively), above phi in both. The SBP/DBP ratio in daytime was higher in the RHTN group (p < 0.0001) (figure 1). The DBP/PP ratio in RHTN was lower in the 24-hour period and during nighttime in T2DM (p = 0.0012; p = 0.0189, respectively) (figure 2). There was no significant difference between T2DM and RHTN groups for DBP/PP ratio in daytime. Conclusion: The phi deviations found in T2DM are greater than those observed in RHTN. These differences may be attributed to the difference in blood pressure values between the groups and reduced nocturnal SBP dipping in patients with RHTN. Future studies using the deviations of the golden ratio are needed to validate the information obtained from this mathematical proposal. 110081 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiology of Risk Factors for Heart Failure in Children and Adolescents in Brazil between 2021 and 2022 LARISSA SILVA FERREIRA1, Aurea Nathallia Gomes de Souza (Souza, ANG)1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira (Oliveira, CS)1, Cecilia Rodrigues Viana1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Vinicius Maciel Vilhena1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa (UNIFAP) Introduction: Cardiovascular diseases are the major causes of death in Brazil. Among the most likely risk factors for the development of these diseases are: arterial hypertension (SAH), dyslipidemia, diabetes mellitus (DM), obesity and physical inactivity. With the changes in life habits in Brazil and in the world, high-calorie dietary changes and the decrease in physical activity among children and young people stand out, which raises an alert for the increased probability of developing diseases in the cardiovascular system in the first two decades of life. Objective: To analyze the mortality rate of children and adolescents due to heart failure in children and adolescents in Brazil, with data from 2021 and 2022. Method: Cross-sectional epidemiological study on the mortality rate of individuals aged 0 to 19 years, due to heart failure cardiac arrest, based on data extracted from the Information Technology Department of the Unified Health System (DATASUS). Results: Between 2021 and 2022, the mortality rate from heart failure before the age of 19 was 7.51% and increased numbers were observed in children under 1 year (9.18%) and between 15 and 19 years (9.83%). With regard to Brazilian regions, the Midwest region has the highest mortality rate (10%), while the Northeast region has the lowest percentage (6.97%). In addition, the rate is higher in children under 1 year old (10.67%) and decreases with age, increasing again from 10 to 14 years old (6.29%) and until reaching 15 to 19 years old (8.75%). This rate is higher in males (8.57%). Finally, the indigenous are the most affected (18.75%) and the yellow ones the least (5.26%). Conclusions: In the child and adolescent population, there was a predominance of males and individuals aged less than 1 year and 15 to 19 years in all data evaluated. Thus, it is understood that changes in habits are increasingly affecting a younger population. This shows the need to invest in health promotion policies for the prevention of cardiovascular diseases, a need reinforced by the high cost of assisting modifiable factors such as diet and physical activities. 110360 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Tongue Inflammation is Associated with Higher Intensity of Immunostaining for IL-1 in Aortic Arteries: Autopsy Study BEATRIZ JUNQUEIRA MATTAR1, Bruno Henrique dos Reis Souza Oliveira1, Kathia Maria Duarte Ono1, Thiago Lima Pereira2, Renata Margarida Etchebehere2, Rodrigo Cesar Rosa2, Sanivia Aparecida de Lima Pereira1 (1) Universidade de Uberaba UNIUBE; (2) Universidade Federal Do Triangulo Mineiro UFTM Introduction: Atherosclerosis is an inflammatory disease of the arteries responsible for a high rate of morbidity and mortality worldwide. Objective: To associate the histopathological and immunohistochemical aspects of tongue inflammation with aortic and coronary atherosclerosis in autopsied humans. Methodology: A total of 4,378 autopsy reports were analyzed and all cases where there were stored fragments of the tongue, aorta and coronary artery of the same individual were selected (n = 16). Morphological and immunohistochemical evaluation was performed for IL-1 beta, IL-6, TNF alpha and IFN gamma. Results: IL-1 in the aorta was associated with the following parameters evaluated in the tongue: IL-6 (p = 0.031); inflammation (p = 0.047); spongiosis (p = 0.018); lymphocytic exocytosis (0.003). IL-6 in the tongue was associated with IL-1 (p = 0.031), IL-6 (p = 0.016) and TNF-alpha (p = 0.016) in the aorta. Tongue exocytosis was associated with IFN gamma in the aorta (p = 0.003). Conclusion: Inflammation and higher immunostaining by IL-6, TNF-alpha and IFN gamma on the tongue are associated with higher immunostaining by IL-1 in atherosclerotic plaques of the aorta arteries. Therefore, knowing that IL-1 is a pro-inflammatory mediator associated with the development of atherosclerosis and that infectious agents are the major causes of inflammation in the tongue, we suggest that prevention and treatment of lingual infections could reduce the risk of atherosclerosis. Thus, these simple and low-cost measures could help prevent the atherosclerotic process, reducing the morbidity and mortality rates associated with this disease. However, further studies are needed in order to corroborate our findings. 110356 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION 3D Printing in Teaching Cardiac Embryological Development CAMILA PIENTZNAUER SOARES MONTE VIANNA1, Claudio Tinoco Mesquita1, Juliana Cadilho da Silva Abrantes1 (1) Universidade Federal Fluminense (UFF) Introduction and/or Fundamentals: 3D printing has proven to be a resource in healthcare through the creation of models of organs and structures with various applications. In cardiology it is possible to use this technology both in the educational area and in surgical planning. In education, an important application of this tool is the printing of three-dimensional embryological models of the formation of the heart, in order to provide a better understanding of human embryology and congenital heart defects. Thus, 3D printed embryological models can provide active learning by visualizing the stages of heart formation in a three-dimensional way, being an innovative didactic resource in embryology and cardiology classes. Objective: We aimed to describe and analyze the improvements of the application of 3D printing in teaching cardiac embryology to health care students. Materials and Methods: At the university we have a digital fabrication laboratory (Fab Lab) that has a GT MAX 3D FDM printer, which builds models by heating and extruding PLA and ABS filaments. These models were digitally modeled by the lab's multidisciplinary team using the Sculptris software and saved in STL format by analyzing images from books and articles in the area. Three embryological cardiac structures have already been printed: cardiac tubes and cardiac tube folding. The printed models are being used for teaching embryology to undergraduate students through face-to-face seminars in the lab. Results: The classes resulted in in-depth teaching of the structures of the heart at different stages of its formation, focusing on the visualization of structures, as well as stimulating the sciences and technologies applied to medicine. Through the three-dimensional visualization of the structures, the students obtained a better understanding of the embryological development of the heart, as well as of its malformations due to failures in this process. In addition, the understanding of the initial formation of the heart helped to better understand the anatomy of the adult heart. Conclusions: The Fab Lab has been of great value and interest to the academic-scientific community. The experience with the 3D models of the heart in teaching embryology and anatomy shows the great potential of this tool allowing a multidisciplinary integration that serves as a stimulus to attract young students. 110371 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Elevated D-Dimer as a Marker for Thromboembolic Events in Pediatric Patients with COVID-19: A Systematic Review JADE ZARICHTA COSTA1, Pietro Preis Casagrande2, Vitor Henrique Macarini2, Josue Barbosa2, Franciely Vanessa Costa3, Maira Cola4, Roberta de Paula Martins1 (1) Laboratorio de Bioquimica Patologica, LABIP, Departamento de Ciencias da Saude, Centro de Ciencias, Tecnologias e Saude, Universidade Federal de Santa Catarina, UFSC, Campus Ararangua.; (2) Academico do Curso de Graduacao em Medicina, Departamento de Ciencias da Saude, Centro de Ciencias, Tecnologias e Saude, Universidade Federal de Santa Catarina, UFSC, Campus Ararangua.; (3) Departamento de Ciencias da Saude, Centro de Ciencias, Tecnologias e Saude, Universidade Federal de Santa Catarina, UFSC, Campus Ararangua.; (4) Grupo de Gestao em Riscos e Desastres, Departamento de Ciencias da Saude, Centro de Ciencias, Tecnologias e Saude, Universidade Federal de Santa Catarina, UFSC, Campus Ararangua. Introduction: Pediatric patients may develop Multisystem Inflammatory Syndrome (MIS-C) in severe cases of COVID-19, a clinical condition that is poorly described yet and may cause cardiovascular changes, persistent fever, skin manifestations, and coagulopathies. Objective: To determine whether elevated D-dimer levels are a risk marker for the development of thromboembolic events in the pediatric population with COVID-19. If so, D-dimer levels could be used to determine prophylactic anticoagulation measures if needed. Methods: This systematic review was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and registered in the PROSPERO Database of Systematic Reviews under CRD42022298330. The last update of the database search was on December 14, 2021, resulting in 79 documents for analysis. Inclusion criteria were: academic articles (case series, cohort studies, and case controls) on patients aged up to 21 years, in English, Portuguese, and Spanish; the databases used were PubMed, Scopus, MEDLINE/Bireme (Virtual Library of Health - VLH), Web of Science, and EMBASE, queried by topic, keywords, or abstract. Bibliographic reviews, books, nonacademic research, case reports, and content in languages other than those indicated were excluded. All articles were independently reviewed by all authors using the Joanna Briggs Institute (JBI) checklist and critical appraisal for risk of bias. Disagreements were resolved through discussion within the group. Six of the articles used were rated as low risk of bias and one was rated as moderate risk. Results: From the 79 articles found, only 7 were selected for analysis. Among these seven articles, only one had patients with thromboembolic events. In the other articles, D-dimer levels were elevated but were considered controversial in predicting events, with no clear association between the magnitude of D-dimer change and the magnitude of thrombosis risk, as the level tended to increase in all inflammatory diseases. Conclusions: Although D-dimer is used for adults, it was not a good parameter for assessing the risk of thromboembolic events in individuals younger than 21 years. The main shortcomings are that D-dimer is elevated in many patients even without the occurrence of thromboembolic events and increases with any type of inflammation, therefore is not a specific marker. 110836 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Prevalence of Diabetes in Adults of Santiago Island -Cabo Verde KELLY ANNY FERNANDES MASCARENHAS 1 (1) Instituto Politecnico de Castelo Branco Introduction: Diabetes are defined as a metabolic disorder characterized by insufficient insulin production or by the incapacity of the body in using them. Consequently, it results in an increase in glucose levels in the blood, being type II diabetes the most common one. It's considered an important risk factor for cerebrovascular pathologies development such as acute myocardial infarction and cerebral vascular accident. In Cabo Verde, according to the National Survey on the Risk Factors of the Non-Transmitted Diseases (SNTD II) 2020, 3.9% of the adult population of Cabo Verde was diagnosed with diabetes, being the females the most predominant one, and 16.6% of them with the range between 60-69 years of age. Objectives: To compare the results of measured diabetes through questionnaire application as well as evaluated diabetes through capillary glycemia of the adults from the island of Santiago - Cabo Verde. Methodology: The transversal study of population background of 599 participants over 18 years old, from both genders. The data collection took place in October and November 2021, in the nine municipalities of Santiago Verde. It was excluded from the study the individuals of Cape Verdean nationality who have been living for over a year abroad and that have just arrived on Santiago Island in less than 30 days, as well as the individuals with any kind of disabilities that may affect their participation in the study. The data were collected through questionnaires; As for diabetes, it was evaluated through a glucometer. Results: The sample was made of 599 individuals with the age range between 18 and 99 years old with an age average of 42 years of age, 54.8% were female and 45.2% were male. Through a questionnaire, it was possible to verify that 7.5% of the participant population answered they have a diabetes diagnosis 71.1% of females. In the diabetes evaluation carried out through capillary glycemia, we found a prevalence of 4.5% of diabetes, of which 63% are females. In both cases, it was verified that there's a meaningful statistical relationship between diabetes and the age group. Furthermore, only measured diabetes by questionnaire showed there's a meaningful statistical relationship with gender. Thus, we could infer that 3% of diabetics have controlled glycemia. Conclusion: There is a greater rate of prevalence in evaluated diabetes by questionnaire, with the women presenting greater predominance in the adminis. 110459 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Association of Morbimortality and Lymphocytes and Neutrophils in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass in a Public Hospital in Belo Horizonte ISABELLA VICTORIA DA CUNHA PEIXOTO RIBEIRO1, Eduardo Augusto Victor Rocha1, Maria Paula Parreira1, Arthur de Vasconcellos Rocha2, Vitor Lanza Avelar Almeida2 (1) Faculdade Ciencias Medicas de Minas Gerais - CMMG; (2) Faculdade da Saude e Ecologia Humana - FASEH Introduction: Cardiovascular surgeries with cardiopulmonary bypass (CPB) have great associated risk, therefore prognostic markers are very important to help in medical decision. In this study we tried to search for markers that help in the decision making process. Objective: To evaluate variables and relate them to morbidity/mortality in order to find prognostic markers for cardiovascular surgery with CPB. Method: Observational retrospective cohort study through consecutive analysis of 113 medical records of patients over 18 years old undergoing cardiovascular surgery with cardiopulmonary bypass from January 1 to December 31, 2015, at the Hospital Universitario Ciencias Medicas de Minas Gerais, in the city of Belo Horizonte, MG - Brazil. We evaluated 32 variables relating them to intensive care stay, hospital stay and mortality. Results: EuroScore II, preoperative creatinine, on intensive care unit (ICU) admission and at hospital discharge, reintubation, surgical infection and return to CPB were statistically significant variables. The number of lymphocytes at ICU admission, above 1263.9 was a statistically significant variable in relation to mortality. These results, except the lymphocyte values, were expected to be related to death. However, the values of lymphocytes collected at the ICU entrance, is an interesting finding and is not in the algorithms for prognostic evaluation in cardiovascular surgery. The study has some limitations due to the small number of participants in the study, because it was done in a single center, and because it has only one year of data collection. However, this study brings a new data, which may be an important prognostic marker in cardiac surgery. Conclusion: The value of lymphocytes above 1263.9/mm3, in addition to Euroscore II, Creatinine in the pre, per and postoperative, infection, return to CPB, showed a significant relation with mortality in cardiovascular surgery with CPB. 110468 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Determinants and Prognostic Value of In-Hospital Infection in Patients Waiting for Permanent Pacemaker Implantation MATHEUS CANDIDO BARBOSA1, Willian Cirillo1, Fernando Piza1, Marcio J.O. Figueiredo1, Odilson M. Silvestre2, Miguel M. Fernandes-Silva3, Roberto Schreiber1, Matheus F.R.A. Oliveira1, Otavio R. Coelho-Filho1, Jose R. Matos-Souza1, Andrei C. Sposito1, Wilson Nadruz Jr.1 (1) Department of Internal Medicine, School of Medical Sciences, State University of Campinas, Sao Paulo, Brazil.; (2) Federal University of Acre, Rio Branco, Brazil.; (3) Federal University of Parana, Curitiba, Brazil. Background: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. Methods: We retrospectively evaluated 905 consecutive patients (68.2 +- 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. Results: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified implantation of temporary pacemaker, diabetes, hospitalization >3 days, heart failure and complete atrioventricular block as independent predictors of pre-PPM-HI. The generated score (range 0-9.9) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.702 [0.653-0.751]. Patients with score >=7.5 had 12-fold greater risk of developing pre-PPM-HI than those with score <2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.86 [1.16-7.06], p = 0.022) as compared with their counterparts. Conclusions: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event. 110476 Modality: E-Poster Scientific Initiation - Non-case Report Category: PHYSIOTHERAPY Photobiomodulation at 808nm in the Induced Fatigue of the Triceps Sural Muscle of Physically Active People. Double-Blind Randomized Study LUCAS CONSOLAIO DE ASSIS1, Lucas Consolaio de Assis1, Liz Maria Xavier de Oliveira2, Cristiane Rodrigues Pedroni3 (1) Universidade Estadual Paulista "Julio de Mesquita Filho" - UNESP, Marilia, Faculdade de Filosofia e Ciencias (FFC - Marilia, SP); (2) Centro de Estudos e Reabilitacao (CER - UNESP, Marilia - SP); (3) Laboratorio de Pesquisa em Ortopedia e Recursos Terapeuticos (LAPORT - Unesp, Marilia) Dysfunction or fatigue of the triceps surae muscles can lead to a defect posture, muscle contracture, fiber ruptures, contusion and injuries related to excessive and repetitive dorsiflexion. Photobiomodulation is a well-studied resource for reduce fatigue and the risk of muscle injuries, being a treatment option and a effective method also for improving muscle performance. Purpose: To investigate the effect of photobiomodulation on muscle performance and recovery after the installation of triceps surae fatigue in physically active people. Methods: Randomized double-blind study, with 14 healthy and physically active subjects, of both sexes, aged between 18 and 30 years, randomly divided into two groups: irradiation and placebo. were carried out the Y Balance Test, manual dynamometry and the electromyographic exam to verify the lower limb performance, strength and electrical activity respectively. In Then, the adapted Bruce protocol and fatigue protocol were applied to the triceps surae, and then active photobiomodulation or placebo according to the group. used the equipment Cluster LASER infrared with 4 diodes, wavelength 808 nm, 120 mW output power, continuous mode emission and total energy (cluster - 4 points) equal to 60J. The effect of therapy between the groups was verified through the values of performance on YBT, strength values by dynamometry and by RMS and index values of fatigue calculated by the median frequency of the electromyographic signal. Results: No significant differences were observed in the intergroup comparison and when compared pre and post in the evaluations of YBT (p = 0.46), muscular strength (p = 0.73) and in the electromyographic behavior of mean RMS values (p > 0.05) and fatigue index (p > 0.05). Conclusion: The photobiomodulation protocol applied after muscle fatigue proposed for the gastrocnemius muscle was not enough to change the parameters of lower limb performance, muscle strength and electromyography. 112438 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Effect of Beta-Blockers and Losartan for Preventing Aortic Dissection in Marfan Syndrome: A Systematic Review MARIA HELOISA BEZERRA VILHENA1, Barbara Vilhena Montenegro1, Lorena Souza dos Santos Lima1, Hillary Ferreira Parnaiba1, Natalia Fernandes Ribeiro1, Michelle Sales Barros de Aguiar1 (1) Instituto Michelle Sales Introduction: Use of antihypertensive medication in Marfan Syndrome (MFS) aims to prevent one of the worst outcomes, aortic dissection. Beta-blockers are well-established drugs in this context, however, a possible response to the use of losartan has attracted the attention of researchers. Objective: To describe the effect of beta-blockers and losartan for preventing aortic dissection in MFS. Methods: This systematic review is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol. PUBMED and Cochrane databases were searched, using the descriptors "Aortic dissection", "Beta-blocker" and "Marfan Syndrome" combined with the Boolean operator "AND". Inclusion criteria were: published in the last 5 years, full text available, clinical trials, randomized trials, books and documents. Exclusion criteria were articles on Loeys-Dietz Syndrome. 116 articles were identified, of which 7 met the inclusion criteria. After checking the studies, a careful reading was carried out, verifying the PRISMA protocol checklist, in order to obtain the qualitative results of the systematic review. Results: According to a randomized study carried out in 2018, the use of atenolol for 3 years by patients with MFS caused a decrease in aortic root stiffness by lowering heart rate (P = 0.01). In the losartan group, no significant differences were observed (p = 0.31). However, a clinical trial was carried out in 2018, in which no significant differences were observed in the increase in the diameter of the aortic root between losartan group (95% CI: 0.2 to 0.5 mm/year) and atenolol group (95% CI: 0.3 to 0.6 mm/year). A study carried out in 2020 in the Netherlands reports that the group of patients using beta-blockers exclusively (n = 124) had 11 cases of aortic dissection, while the group using combined therapy with beta-blockers and losartan had 3 evolutions for this event during the eight years of study. In another 2020 finding, patients with MFS who had the CC genotype and were in use of atenolol had a better rate of improvement than patients who were using losartan (interaction P = 0.002; -0.20 +- 0.02 vs -0.07 +- 0.02; P < .001). Conclusion: Combined therapy of atenolol and losartan has beneficial effects when compared to losartan alone, although there are no significant clinical differences on the exclusive use of losartan. There are insufficient randomized studies to prove the effectiveness of this therapy in acute aortic dissection in MFS. 110549 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Factors Associated with Carotid Intima-Media Thickness in Adults and the Elderly in a German City in Southern Brazil NATALIA MERHEB HADDAD1, Suhen Aquino de Liz2, Marcello Ricardo Paulista Markus3, Maria Eduarda Venera4, Ernani Tiaraju de Santa Helena5, Clovis Arlindo de Sousa6, Alan de Jesus Pires de Moraes1 (1) Universidade do Vale do Itajai; (2) Programa de Pos-Graduacao Stricto Sensu em Saude Coletiva. Universidade Regional de Blumenau; (3) Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany. German Center for Diabetes Research (DZD), partner site Greifswald, Gre; (4) Departamento de Educacao Fisica. Universidade Regional de Blumenau, Blumenau, Santa Catarina, Brasil; (5) Departamento de Medicina. Programa de Pos-Graduacao Stricto Sensu em Saude Coletiva, Universidade Regional de Blumenau; (6) Departamento de Educacao Fisica, Programa de Pos-Graduacao Stricto Sensu em Saude Coletiva, Universidade Regional de Blumenau Background: Carotid intima-media thickness (CIMT) is a marker of atherosclerosis and a predictor of cardiovascular disease, however, there are few studies on factors associated with CIMT in specific populations. Objective: The goal was to analyze the prevalence and factors associated with CIMT among adults and the elderly people in a German city in southern Brazil. Method: Cross-sectional population-based study, with 2488 people between 20 and 79 years old, from the Study of Health in Pomerode - SHIP-Brazil. The CIMT was evaluated by ultrasonography and the altered thickening was values >=0.90 mm. The independent variables involved sociodemographic aspects, lifestyle, health conditions and chronic diseases. Crude and adjusted Poisson regression with estimates of prevalence ratios (PR) and confidence intervals were used. Results: The prevalence of high CIMT was 10.9%, higher in the elderly (42.5%) when compared to adults (4.7%). Among adults, male (PR = 1.75), ex-smoker (PR = 2.06), smoker (PR = 2.15), high waist-to-hip ratio (PR = 2.09), hypertension (PR = 2.19), and carotid plaque (PR = 2.34) were associated with elevated EMIC. In the elderly, male (PR = 1.33), insufficiently active (PR = 1.39), high waist-to-hip ratio (PR = 1.34) and plaque (PR = 1.54). Conclusion: Actions to prevent and control high CIMT involve increase the level of physical activity, smoking cessation, preventing of hypertension and excess abdominal fat. 111061 Modality: E-Poster Scientific Initiation - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Resilience in Patients with Chronic Coronary Syndrome Assisted in Public and Private Healthcare Networks: Are there Differences? JOSE ICARO NUNES CRUZ1, Adelle Cristine Lima Cardozo1, Giulia Vieira Santos1, Jade Soares Doria1, Mariano Cesar de Souza Reis1, Gabriela de Oliveira Salazar1, Bruna Souza Matos de Oliveira1, Juliana Maria Chianca Lira1, Diego Maldini Borba de Lima1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital; (3) Primavera Hospital Introduction: Resilience refers to the ability to develop adequately, even when facing difficulties, and can be an important factor in health promotion, especially in chronic diseases. Objectives: To evaluate how resilience behaves among patients with Chronic Coronary Syndrome (CCS) seen in the public and private healthcare networks. Methods: This is a cross-sectional, analytical study, whose sample included patients with CCS assisted at cardiology outpatient clinics of two public hospitals and one private hospital. The patients were divided into two groups, according to the healthcare system: I) Public; II) Private. Participants completed the Connor-Davidson Resilience Scale (CD-RISC-10), composed of ten items, each one presented as an ordinal scale from 0 to 4. The total resilience level comprises the sum of the responses from each item, and thus ranges from 0 to 40. The results were described in terms of means and standard deviations and the statistical analysis was performed using Fisher's Exact test and Student's T-test, with significance level set at 0.05. Results: 53 patients with CCS were included, 69.8% from the Public group and 30.2% from the Private group. The gender distributions were not different between groups (p > 0.05), however the Public group had a lower mean age than the Private group (60.2 vs. 66.9 years; p < 0.05). Patients with CCS assisted at the public system showed a lower level of total resilience than patients assisted at the private healthcare system (26.4 vs. 31.9; p < 0.05). The CD-RISC-10 showed that patients in the Public group believed less that they could achieve their goals compared to the Private group (3.0 vs. 3.8; p < 0.05). When presented with the statement "I am not easily discouraged by failures", Public group patients had lower mean scores on the scale (2.9 vs. 3.7; p < 0.05), which denotes that this statement is less true for this group compared to the Private group. Conclusions: The results show that patients with CCS assisted in the public healthcare system have a lower level of resilience than patients assisted in private settings. Differences in resilience levels between the groups are concentrated in the belief in the possibility of achieving personal goals (lower for the Public group), and in discouragement in the face of failures (higher for patients in the Public group). 110589 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Risk Factors Related to Congenital Heart Diseases: An Analysis of the Unified Health System Database in the State of Parana, Brazil (Datasus) MARIA JULIA DA SILVEIRA MARQUES1, Maria Julia da Silveira Marques1, Audrei Pavanello1 (1) Unicesumar Congenital heart diseases (CHDs) describe a set of abnormalities of the heart and great vessels which are present at birth and are associated with great physiological impact on the neonate. The etiology of those malformations is multifactorial, including genetic and environmental factors, maternal obesity, pre-gestational diabetes mellitus and the use of potentially teratogenic drugs like retinoic acid. These causes seem to influence the development of the fetal cardiovascular system, causing cardiac and great vessel anomalies and consequently, a functional disorder of this system. Considering these factors, the objective of this study is to correlate the risk factors associated with poor fetal cardiovascular development, through an analysis of the Unified Health System database (DATASUS). The data used were collected from the DATASUS Information System for Live Births (SINASC) platform with the help of Software R (version 4.1.3) and RStudio (version 2021.09.0 + 351). For data collection, the R microdatasus package was used, with the referring period of 2007 to 2020 in the state of Parana. Data were filtered using the R tidyverse package, with 1135 births with congenital heart anomalies registered during this period (ICD Q200 to Q250). For comparison, 5676 observations of non-anomaly neonates chosen from random data were used. The analysis was performed using the rpart package, where a classification tree was constructed crossing the variables: weeks of pregnancy, maternal age, birth weight, sex and race against the presence of congenital anomalies. Data were plotted using the rpart.plot package. With the analysis of the data, through the softwares R and RStudio, the following results were obtained: in order of greater to lesser relevance, the factors that influence the development of CHD are the birth weight (184.497256), the type of delivery (40.688717), gestational age (29.954032), mother's age (21.551755), race (2.277806) and sex of the neonate (1.405119). Greater attention is necessary to these factors, aiming possible prevention and early management of this condition. 110627 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk Profile in Patients with Metabolic Dysfunction-Associated Liver Disease MARIA EDUARDA DE ALMEIDA OLIVEIRA1, Daniele Araujo de Azevedo Coutinho2, Sergio Augusto Antonio3, Davi Cassiano Costa4, Vanessa da Costa Rodrigues5, Raphael Carreiro Moura6, Maria Auxiliadora Saad7, Carlos Roberto Moraes de Andrade Junior8, Priscila Pollo Flores9, Debora Vieira Soares10 (1) Universidade Federal Fluminense; (2) Universidade Federal Fluminense; (3) Universidade Federal Fluminense; (4) Universidade Federal Fluminense; (5) Universidade Federal Fluminense; (6) Universidade Federal Fluminense; (7) Universidade Federal Fluminense; (8) Universidade Federal Fluminense; (9) Universidade Federal Fluminense; (10) Universidade Federal Fluminense Background and Aims: fatty liver desease (NAFLD) is the most frequent cause of hepatic disease, with a world prevalence of 25%. There seems to be a connection between the gravity of NAFLD, endothelial dysfunction, atherosclerosis and the increase in cardiovascular mortality events. This study aimed to asses cardiovascular risk profile of individuals with NAFLD. Methods: Prospective observational analytical study. Adults with established risk for the development of NAFLD were selected, such as: type 2 Diabetes Mellitus (DM), metabolic syndrome and obesity are selected. Non-invasive assessment of liver steatosis and fibrosis was performed by hepatic ultrasound (FLI-score) and transient elastography. We assessed the frequency of the cardiovascular disease, according to the clinical history, common carotid artery intima-media thickness (IMT) using an ultrasound examination of the carotids and a stratification of the cardiovascular risk by a specific algorithm. Results: All data are presented in median (IQR) and n(%): 31 individuals, 25(80,65) female, performed the ultrasound examination of the carotids. Chronological age 67,5(53,75-66,5) years, vascular age 85(46-85)years. Right IMT 0,805(0,54-0,79)cm and left IMT 0,85(0,53-0,75)cm, 8(25,81) had atherosclerotic plaques. We observed: Hepatic Steatosis in 28(90,32), being 6 (19,35) mild, 12(38,71) moderate and 10(32,25) severe. Liver Fibrosis in 8(25,81), being 2(25,00) moderate and 6(75,00) advanced or cirrhosis. Systemic Arterial Hypertension 24(77,42), DM 18(58,06) and Dyslipidemia 22(70,97). Conclusion: Our data shows a high frequency of hepatic fibrosis and atherosclerotic disease in the collected sample. 110660 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Mechanical or Biological Valve Prostheses for Aortic Valve and Mitral Valve Replacement: Analysis of the Patients Operated in a Tertiary Health Center between 2010-2021 AMANDA BERGAMO MAZETTO1, Eduarda Druck Magadan2, Rafael Aprecido Garcia2, Hellen Cristina Cinesio1, Abdalla Hoelz1, Julien Ramos Stein1, Berta Paula Napchan Boer1, Paula Lavitola1, Ana Flavia Diez de Andrade1, Flavio Tarasoutchi1 (1) Instituto do Coracao da Faculdade de Medicina da USP; (2) Escola de Medicina da PUCRS Introduction: Valvular heart disease is a public health problem in Brazil, mainly due to the high prevalence of rheumatic fever, resulting in the need for surgical procedures to repair the valvular disease. Choosing the type of prosthesis in some situations remains a challenge, since it is necessary to consider the patient's age, preferences and socioeconomic conditions, besides thromboembolic, hemorrhagic and new valve replacement risks. With the development of the Valve-in-Valve procedure, the risk of reoperation has decreased considerably and, therefore, the ideal type of prosthesis for the patient remains a controversial topic. Objectives: The objective of the present study is to analyze the type of prosthesis that is most chosen in the surgical treatment of valve replacement in aortic or mitral position in patients operated in a tertiary health center. Methods: Medical records were reviewed of patients undergoing valve replacement surgery in aortic and mitral position between 2010 and 2021. Results: There were 5333 patients with a mean age at the time of surgery of 57.8 years. Among the analyzed patients, 49.9% of the individuals were female. Regarding the indication of the procedure, elective surgery was the indication in 82.2% of the cases, and urgent and emergency cases, in 17.8% of the cases. In total, 91.4% of biological prostheses and 8.6% of mechanical prostheses were placed. A total of 3042 (57%) aortic valve replacements were performed alone, of which 2876 (94.5%) were biological and 166 were mechanical (5.4%). In the mitral position, there were 1889 (35.42%) valve replacements alone, of which 1654 (87.5%) were biological and 235 (12.4%) were mechanical. In the study, 402 (7.53%) patients with double lesions (aortic and mitral) underwent surgery, 354 (88.1%) being biological and 48 (11.9%) mechanical. Conclusion: Biological prosthesis is the model of choice in our service. The main factors that justify this choice are the age of our patients, the socioeconomic and educational conditions that often limit the possibility of anticoagulation, the better quality of life without the need for anticoagulation, and the lower risk of current reoperation with the Valve-in-Valve procedure in biological prostheses. 110676 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Prevalence in the Number of Hospitalizations for the Treatment of Aortic Aneurysms in Brazil between January of 2011 and December of 2021 PABLO RIBEIRO MIRANDA BARBOSA1, Brunna Machado Medeiros1, Gabriel Dias de Oliveira1, Gustavo Fornachari1, Matheus Giacomelli da Trindade1, Marcelle Telasca Patzlaff1, Lucas Alvares de Souza1, Ricardo Augusto Oliveira Mendes1, Mikaelle Taina Bertoli1, Bruno Noschang Blaas2 (1) Federal University of Pelotas (UFPEL); (2) Federal University of Sao Paulo (UNIFESP) Introduction: An aneurysm is the dilation of a blood vessel that is greater than 50% of its normal diameter. It induces a fragility in the arterial wall and can trigger severe outcomes, such as the compression of adjacent structures or rupture of the blood vessel itself . In Brazil, the most prevalent cases of aneurysms come in the form of an abdominal aortic aneurysm (AAA). This is more frequently found in elderly patients, with other risk factors in addition to age being: smoking, systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus. It is 4 to 6 times more frequent in males. Furthermore, ultrasonography (USG) AAA screening is recommended for men between the ages of 65 and 75, who are smokers or who have first-degree relatives with a history of AAA. As for women, screenings are recommended for those with a family history of AAA where a 1st degree relative has had a diagnosis. Objective: Describe the annual prevalence in the number of hospitalizations for the treatment of aortic aneurysms (AA) in Brazil between January of 2011 and December of 2021. Methodology: Descriptive cross-sectional study based on a quantitative approach to the frequency of hospital admissions for treatment of aortic aneurysm in Brazil between January of 2011 and December of 2021. Data regarding hospitalizations was collected from the Hospital Information System of the Unified Health System in Brazil, colloquially known as SIH/SUS. Results: In 2011 there were 2,892 registered hospitalizations for the treatment of AA, followed by 2,906 in 2012, 3,184 in 2013, 3,440 in 2014, 3,815 in 2015, 4,061 in 2016, 3,907 in 2017, 4,184 in 2018, 4,456 in 2019, 3,733 in 2020 and 4,092 cases in 2021. Thus, we conclude an increase of 41.4% in the number of cases between 2011 and 2021. Conclusion: We observed an increase of more than 40% in hospitalizations for the treatment of AA during the study period. However, during the same period, it is important to note that there was a population increase of 10.9%. As a result, we can speculate that there was an increase in diagnostic screening, in addition to a higher incidence of comorbidity such as obesity, diabetes mellitus, dyslipidemia and hypertension. In conclusion, this article is not able to infer specific causality for the number of hospitalizations, thus suggesting that further studies in this topic are needed. 110768 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM SARS-COV-2 Pandemic and the Morbimortality of Acute Myocardial Infarction in the Northeast Region of Brazil ANA FLAVIA BOTELHO1, Caroline Link1, Larissa Almeida Busnello1, Paola Goncalves Moreira de Oliveira1, Francielle Nocera Viechineski1, Bruna Kara1, Ana Carla Dlugosz1, Alice Magro Koscianski1, Camilla Mattia Calixto1, Julia Henneberg Hessman1, Mario Claudio Soares Sturzeneker1 (1) Universidade Estadual de Ponta Grossa Introduction: Worldwide, ischemic heart disease is the most common cause of death, and, in this context, acute myocardial infarction (AMI) is a significant public health problem. The SARS-CoV-2 pandemic caused changes in the dynamics of care in emergency units and consequently influenced morbidity and mortality from AMI. Purpose: To estimate the impact of the SARS-CoV-2 pandemic on morbidity and mortality from AMI in the Northeast region through the analysis of DATASUS data. Method: In the period from 2018 to 2021, subdivided into pre-pandemic (11/2018 to 02/2020), pandemic (03/2020 to 06/2021), the peak of the pandemic (12/2020 to 05/2021), first and second trimester of the peak (12/2020 to 02/2021 and 03/2021 to 05/2021) and mass vaccination period (06/2021 to 12/2021), were evaluated in general and by gender, hospitalizations, deaths, mortality rate (percentage obtained by dividing the number of deaths by the number of hospitalizations), calculating the average of each variable and comparing the respective periods, with differences expressed as percentages. Results: In the pandemic period, the number of hospitalizations reduced by approximately 4% compared to the pre-pandemic period. There is an increase in the number of hospitalizations in the second trimester of the peak and the period of mass vaccination, with an increase of 2% and 15%, respectively. Compared to the pre-pandemic period, the average hospital stay was lower in the pandemic and first trimesters of the peak periods (12.3%). There was a reduction in the number of deaths in the pandemic (1%) and the first trimester of the peak (5%) compared to the pre-pandemic period. There is an increase in the number of deaths in the second trimesters of the peak, especially in the mass vaccination period (13%) compared to the pre-pandemic period. Regarding gender, the number of hospitalizations was higher in men, and the mortality rate was higher in women throughout the period evaluated. Conclusions: Social isolation and functional changes in the health system caused by the SARS-CoV-2 pandemic influenced morbidity and mortality from AMI in the Northeast region of Brazil, and mass vaccination culminated in the return to characteristics similar to the pre-pandemic period. 110789 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Prevalence of Subclinical Atherosclerosis with Altered Coronary Calcium Score in a Santa Catarina Microregion JULIA FARENZENA ZAPELINI1, Manuela Matheus1, Samantha Cristiane Lopes1, Franciani Rodrigues da Rocha1, Ottavia de Vasconcelos Zainho Helbok1, Caroline de Oliveira Fischer Bacca1 (1) UNIDAVI - Centro Universitario para o Desenvolvimento do Alto Vale do Itajai Introduction: Considering that some cardiac death occurs in asymptomatic patients, it is very important to identify subgroups of people with a high risk of cardiovascular arterial diseases (CAD). The coronary artery calcium (CAC) is a marker that identifies the atherosclerotic burden, which is related to the incidence of CAD. Objectives: Evaluate the prevalence of subclinical atherosclerosis defined as altered CAC, recognizing the most prevalent risk factors. Methods: Cross-sectional study with 547 patients who underwent CAC between Jan/16 and Dec/21. Statistical analyses were performed using SPSS employing Fisher's exact test or Pearson's chi-square test. The level of statistical significance was set at p < 0.05. Results: The mean age was 52.3 +- 8.9 years. Including CAC, the mean age was 70.5 +- 13.4 years and the CAD risk was 9.5 +- 8.8%. There was correlation between hypertension (SAH) and CAC > 400 (p = 0,04; p < 0,05); and diabetes (DM) and CAC > 400 (p = 0,01; p < 0,01). When the CAC was adjusted in percentiles, the presence of SAH was relevant with the percentile >75 (ra = 4,8; p < 0,01), and dyslipidemia with the percentile 50-75 (ra = 2,7; p < 0,01) and >75 (ra = 2,5; p < 0,01). The absence of SAH (ra = 4,3; p < 0,01) and dyslipidemia (ra = 4,1; p < 0,01) were protective factors, since they showed significance with the 0 percentile. Conclusions: Elevated CAC showed relevance with DM, SAH and dyslipidemia, while the absence of SAH and dyslipidemia were cardiovascular protection factors. 110797 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOGERIATRICS What are the Results and Characteristics of the Head-Up Tilt Test in the Elderly? ANA GABRIELA PONTE FARIAS1, Arnobio Dias da Ponte Filho4, Francisca Tatiana Moreira Pereira4, Vera Marques4, Luis Gustavo Bastos Pinho1, Maria Jacqueline Batista1, Eduardo Augusto Quidute Arrais Rocha3, Ana Rosa Pinto Quidute1, Marcela Albuquerque de Holanda3, Aston Alves de Freitas3, Arthur Holanda Dantas3, Eduardo Arrais Rocha4 (1) Universidade Federal do Ceara; (2) Universidade de Fortaleza; (3) Centro Universitario Christus; (4) Centro de Arritmia do Ceara Introduction: In the elderly, there are several causes of syncope or presyncope, making etiological diagnosis challenging. The relevance of the Head-Up Tilt Test (HUT) in this population has been questioned because of a high incidence of cardiac causes with risk of sudden death. However, dysautonomic causes are also common in this age group, affecting morbidity and mortality. Objective: The aim of this study was to compare the results of the HUT between the elderly (>=60 years old) and non-elderly age groups. Methods: This was a retrospective cohort study, carried out from 2016 to 2021. For comparisons, non-parametric Mann-Whitney/Wilcoxon tests were used, with a significant p-value <5%. The protocols were Westminster or Italian, with the sensibilization phase (1.25 mg sublingual isosorbide) used according to the medical decision during the examination. Results: A total of 2347 tilt tests were analyzed, 61.7% were female, with a median age of 51.1 (31-71). The overall positivity rate was 33.3%, with 43.3% with pharmacological sensibilization (p < 0.01). There were 972 (41.82%) in the elderly group (EG) and 1352 (58.18%) in the non-elderly group (NEG). The positivity rate of EG was lower (p < 0.01); 266 (11.45%) in the EG had positive HUT x 496 (21.24%) in the NEG. The positivity rate with sensibilization in the EG was 27.37% x 20.52% in the NEG (p = 0.008). In the EG, 48 patients (5.04%) had a dysautonomic response x 10 (0.73%) in the NEG (p < 0.001). In the EG, the rates of vasovagal response were 209 (21.97%), distributed as follows: vasodepressor (15.23%); cardioinhibitory (0.92%); mixed (5.86%), while in the NEG, the rates were 466 (33.94%), being vasodepressor (16.94%), mixed (15.90%), and cardioinhibitory (1.26%) (p < 0.001). The rate of complications in the EG was 1.54% x 1.63% in the NEG (p = 0.02), but without serious events. Prodromes were more common 39.86% (539) in the NEG x 31.10% (302) in the EG (p < 0.001). Conclusion: The HUT in the elderly population showed a lower incidence of positivity in the passive phase, however with a higher rate in the sensibilization phase, compared to the non-elderly. The elderly had a higher incidence of dysautonomic responses and a lower rate of prodromes and complications. This method should remain, therefore, as a complementary test in the syncope or presyncope investigation also in the elderly. 110799 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Angiography Quantitative Flow Ratio: A Systematic Review and Analysis of Diagnostic Accuracy LUCAS BONACOSSA SANT'ANNA1, Eduardo Amar Ferreira1, Sergio Livio Menezes Couceiro3, Daniel Chamie4, Fernando Mendes Sant'Anna2 (1) Fundacao Tecnico-Educacional Souza Marques (RJ); (2) Universidade Federal do Rio de Janeiro (Macae); (3) Hospital Santa Izabel (Cabo Frio); (4) Instituto Dante Pazzanese de Cardiologia (SP) Introduction: Fractional flow reserve (FFR) is the gold standard to evaluate severity of coronary stenosis. Quantitative flow ratio (QFR) is a new angiography-based method used to infer FFR. Studies have shown >90% agreement between QFR and FFR. Objective: To conduct a systematic review and diagnostic accuracy analysis of QFR using individual vessel data. Methods: This review follows PRISMA guidelines. MEDLINE, EMBASE and Cochrane Library of Clinical Trials were searched for QFR accuracy studies published until Oct 2020. Inclusion criteria: (a) QFR vs FFR; (b) QFR diagnostic capacity; (c) agreement data between QFR/FFR expressed as dot plots or individual data tables. Graphic data were digitized using a semiautomatic software. QFR/FFR values were dichotomized using cutoff values of <=0.80 for ischemia. QFR diagnostic accuracy was assessed by two logistic regressions superimposed on the same graph to ensure the probability of agreement between QFR and FFR for any QFR value. FFR was the reference standard. Results: 20 studies comprising 5,318 vessels from 4,429 patients were included. Most patients were male (64%) at an age of 66.8 +- 5.2 years. Figure 1A shows FFR distribution and QFR diagnostic accuracy for different QFR ranges. QFR overall accuracy, sensitivity, specificity, PPV and NPV are displayed in Figure 1B. A diagnostic accuracy of 87% was reached for QFR cutoff values <0.71 or >0.86, and 95% or 98% with cutoffs <0.66 or >0.91 and <0.62 or >0.94, respectively . Conclusions: A very good diagnostic accuracy of QFR measures was observed using individual vessel data. QFR can be used to evaluate the severity of coronary stenosis. At less accurate values addition of FFR can improve precision. 110835 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION The Prevalence of Hypertension in Santiago Verde KELLY ANNY FERNANDES MASCARENHAS MASCARENHAS1 (1) Instituto Politecnico de Castelo Branco Introduction: It is estimated that about 1.13 thousand million people around the world are affected by Hypertension (HTN), which causes about 45% of heart disease deaths and 51% of the CVA deaths, more than 8 million deaths per year, and 92 million years of life disability. In Cabo Verde, according to the National Survey about the Risk Factors of Non-Transmitted Diseases (NTDS II) 2020, 20,1% of the population suffer from hypertension. Objectives: To study the prevalence of hypertension in adults residing in Santiago Island - Cabo Verde. Methodology: The transversal Study of the population background in which the data collection took place in October and November 2021, in the municipality of Santiago IslandCabo Verde. It was excluded from the study the individuals of Cape Verdean nationality who have been living for over a year abroad and that have just arrived on Santiago Island in less than 30 days, as well as the individuals with any kind of disabilities that may affect their participation in the study. The data were collected through questionnaires; As for hypertension, it was evaluated using an automated sphygmomanometer. Results: It was studied 599 individuals with the age range between 18 and 99 years old with the age average of 42 years of age, while 54.8% female and 45.2% male. The findings showed that 32.6% of the participants in the study had high blood pressure; 53.8% are female and 46.2% are male. Out of 195 hypertensive participants, it's realized that 34.6% had stage I HTN, 26.2% had stage II HT, 14.1% had stage III HTN and 25.1% had systolic Isolated hypertension. Thus, it was also found that there is a meaningful statistical relationship between HTN, diabetes, and the age group. Conclusion: There is a high prevalence of HTN in the population of Santiago Island - Cabo Verde. 110867 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Nets Release from Peripheral Blood Neutrophils from Patients with Chagas Disease: Correlation with Ecocardiogram Parameters LUANN GABRIEL PORPINO SALES1, Marcelo Augusto Araujo Castro1, Pedro Felipe Alves de Souza1, Valeria Duarte de Almeida1, Eduardo Bulhoes Leopoldo da Camara1, Suyane Maria Paiva Pimenta1, Micassio Fernandes de Andrade1, Cleber Mesquita Andrade1, Thales Allyrio Araujo de Medeiros Fernandes1, Amanda Estevam Carvalho1, Felipe Alves de Lima1 (1) Universidade do Estado do Rio Grande do Norte (UERN) Introduction: The neutrophils are capable of interacting with Trypanosoma cruzi, the etiological agent of Chagas Disease (CD), and release NETs (extracellular Neutrophils traps) causing damage to the myocardium. Objective: To evaluate the correlations between the amounts of NETs released by patients with CD, their clinical forms, with the echocardiographic parameters of these patients. Methods: Retrospective cross-sectional study with conventional sampling. A total of 35 volunteers participated in the research, being 11 healthy individuals and 24 patients with Chagas disease (15 of the indeterminate clinical form and 9 of the cardiac form). The quantification of the formation and release of NETs was performed by means of fluorescence. The identification of clinical forms and the analysis of the echocardiogram were performed by analyzing the filed medical records. The data obtained were processed and statistically analyzed using the GraPad Prism 7.00. Results: Neutrophils from healthy individuals, when stimulated with soluble T. cruzi antigen, release NETs greater than the cells of chagasic patients, both with the clinical cardiac form (* p = 0.0014), as for the indeterminate clinical form (* p = 0.0142). When correlating the concentration of NETs released with the parameters of the Echocardiogram, a negative correlation was observed with the systolic diameter of the left ventricle (r = -0.07998; * p = 0.0097) and with the left ventricular mass index (r = -0.7743; * p = 0.0086), in addition to a positive correlation with the left ventricular ejection fraction (r = 0.6539; * p = 0.0403). Conclusions: Neutrophils from patients with CD release less NETs than neutrophils from healthy individuals and may be associated and contribute to the clinical course of Chagas cardiomyopathy. 110877 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOGERIATRICS Prevalence of Cognitive Dysfunction in Elderly Patients with Ischemic Heart Failure CAROLINA DE CARVALHO MOURY FERNANDES1, Maria Eduarda Borges Matias1, Carolina Jeronimo Magalhaes3, Matheus Dantas Soeiro1, Sabrina Barreto Braga Pires1, Ellen Beatriz Sobral1, Jessica Myrian de Amorim Garcia2, Francisco Bandeira3 (1) Faculdade Pernambucana de Saude; (2) Hospital Agamenon Magalhaes; (3) Universidade de Pernambuco Introduction: The incidence of heart failure (HF) has steadily increased especially due to the aging of the population. One of its main etiologies is the coronary artery disease (CAD). In the elderly there is a high prevalence of cognitive dysfunction, which can be analyzed by mini cog, a short cognitive impairment screening exam. This cognitive dysfunction may be associated with both coronary and cerebrovascular disfunction. Objectives: Analyze the prevalence of cognitive dysfunction in hospitalized patients with ischemic heart failure. Methods: Cross-sectional observational study of inpatients aged >=65 years, hospitalized with HF. The study was conducted in a public Brazilian cardiology teaching center from August 2020 to December 2021. The diagnostic criteria for ischemic heart failure was based on coronary angiography findings, while cognitive dysfunction was evaluated using the Mini-Cog. Results: Our total sample consisted of 198 elderly patients diagnosed with HF, we studied 98 of them that also had CAD, showing the prevalence of ischemic heart failure. The mean age was 72.7 years ranging from 65 to 90, and 56.1% were male. Among the comorbidities, 42.9% had diabetes and 89.8% hypertension. The prevalence of cognitive dysfunction was 59.2% based on the Mini-Cog. Conclusion: There was a high prevalence of cognitive dysfunction among the elderly patients with CAD and HF, that was evident when analyzing using the Mini-Cog. 111798 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Profile of Hospitalization in the Health Unic System in the Municipality of Sao Paulo for Acute Myocardial Infarction in the Year 2021 MAYURI AKEMI RODRIGUES HIGASHI1, Gabriel Ribeiro de Souza1, Rafaela Andrade Penalva Freitas2 (1) UNIVERSIDADE DE SANTO AMARO; (2) INSTITUTO DANTE PAZZANESE DE CARDIOLOGIA Introduction: Despite significant scientific advances and public prevention policies, acute myocardial infarction corresponds to a high rate of hospitalizations and morbidity and mortality. Objective: To analyze and describe the profile of patients who are hospitalized in the city of Sao Paulo for Acute Myocardial Infarction in the year 2021. Methodology: It consists of a descriptive, retrospective, longitudinal epidemiological study, based on the analysis of a secondary source of data, with the aim of the studies being hospital admissions in the Unified Health System of the city of Sao Paulo, in the year 2021, for causes related to diseases. hypertensive As inclusion criteria, all hospital admissions were selected through the Hospital Information System (SIH), through DATASUS. The period studied was the year 2021. The morbidities were separated and selected according to the main hospitalization diagnosis and classified according to the International Disease Code 10 (ICD10), the following being selected: I10 -Essential hypertension, I11 - Hypertensive heart disease, I12 - Hypertensive kidney disease, I13 - Hypertensive heart and kidney disease, I15 - Secondary hypertension. Gender, race/color and age group were also taken into account. Results: During the study period, 2219 hospitalizations were performed for hypertensive diseases, of which 49.2% were male and 50.8% female. Among the target audience of the study, when considering race/color, 35.8% of patients consider themselves white, 8% black, 29.5% brown and 0.2% yellow. 26.5% of the registered admissions had no description of race/color. Regarding the age groups studied, there is a gradual increase in the number of hospitalizations as the observed age group also increases, with the group of patients over 80 years of age having the highest number of hospitalizations, corresponding to 14% of all the hospitalizations. Conclusion: Hospitalizations in the city of Sao Paulo due to hypertensive syndromes were slightly higher in males, most of whom were white and aged over 80 years. 110903 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Features of Enterococcal Endocarditis in a Cardiology Surgical Center in Brazil: A Comparative Analysis NICOLAS DE ALBUQUERQUE PEREIRA FEIJOO1, Mariana Giorgi Barroso de Carvalho1, Thatyane Veloso de Paula Amaral de Almeida1, Ingrid Paiva Duarte1, Leo Rodrigo Abrahao dos Santos1, Rafael Quaresma Garrido2, Giovanna Ferraiuoli Barbosa2, Clara Weskler2, Wilma Golebiovski2, Bruno Zappa2, Marcelo Goulart Correia2, Cristiane Lamas2 (1) Unigranrio/Afya, Rio de Janeiro, Brasil; (2) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (3) Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brasil Introduction/Objectives: Enterococci have increasing frequency as agents in infective endocarditis (IE) due to the population's increasing life expectancy. They are also strongly related to infections acquired in healthcare scenarios. The present study aims to describe episodes of Enterococcal Endocarditis (EE) in a cardiac quaternary referral center, while also comparing them to other cases IE within the cohort. Materials and Methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Patients were identified prospectively. Categorical variables of the EE group were compared to the other patients IE in the cohort by test of proportions. Statistical significance was set in p < 0,05 threshold. Results: Enterococcal Endocarditis was observed in 48 out of 435 (11%) cases, in which 2 out of 48 (4.2%) cases were identified as E.faecium, while E.faecalis accounted for the vast majority (46/48, 95.8%). Patients with EE were significantly older (median age 59 years, IQR 46-65.3) than the remaining of the cohort (median age 46.0, IQR 32.5 -61.0). A higher incidence of EE was observed in patients with coronary artery disease (13/48, 27.1% vs 47/380, 12.4%, p = 0.006), previous cardiovascular surgery (26/48, 54.2% vs 144/385, 37.4%, p = 0.025), coronary artery bypass graft surgery (6/47, 12.8% vs 19/383, 5%, p = 0.031), diabetes mellitus (12/48, 25% vs 43/387, 11.1%, p = 0.006), chronic renal failure, CRF (16/48, 33,3% vs 75/385, 19.5%, p = 0.026), and cerebrovascular disease (6/48, 12.5% vs 23/386, 6%, p = 0.087). EE patients often acquired the infection in hospital (23/48, 47.9% vs 89/386, 23.1%, p < 0.001). Furthermore, data demonstrated that early Prosthetic Valve Endocarditis (PVE) was proportionally more common in patients with EE (9/48, 18.8% vs 38/387, 9.8%, p = 0.06). New conduction abnormalities (11/43, 25.6% vs 43/349, 8.3%, p = 0.017) were more frequent in patients with EE. Discussion: The frequency of EE in our cohort was similar to the literature (5 to 20%). The results define a profile of older patients with multiple comorbidities, especially CRF and diabetes, and a higher proportion of early-PVE. The observed complication of new conduction disturbances may result from PVE. We hypothesize vascular accesses were the portal of entry for enterococci, and special care must be taken with with them, especially in the perioperative period. 110905 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Features of Fungal Endocarditis in a Cardiac Referral Center in Rio de Janeiro, Brazil NICOLAS DE ALBUQUERQUE PEREIRA FEIJOO1, Thatyane Veloso de Paula Amaral de Almeida1, Mariana Giorgi Barroso de Carvalho1, Ingrid Paiva Duarte1, Leo Rodrigo Abrahao dos Santos1, Rafael Quaresma Garrido1, Giovanna Ferraiuoli Barbosa2, Clara Weksler2, Wilma Golebiovski2, Bruno Zappa2, Marcelo Goulart Correia2, Cristiane Lamas2 (1) Unigranrio/Afya, Rio de Janeiro, Brasil; (2) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (3) Instituto Nacional de Infectologia Evandro Chagas, Fiocruz Introduction/Objectives: Fungi, especially candida spp., have become a frequent cause of bloodstream infections, and Fungal Endocarditis (FE) has a bad prognosis with high in-hospital mortality rates. This study aims to describe cases of FE in a cardiac quaternary referral center and compare them to other infective endocarditis (IE) cases within the cohort. Materials and methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Patients were identified prospectively. Categorical variables of the EF group were compared to the other patients with IE within cohort by test of proportions. Statistical significance was set in p < 0,05 threshold. Results: FE occurred in 14/434 (3.2%) of IE cases; Candida spp accounted for 12/434 (2.7%), of which 8/12 (66.6%) were C. parapsilosis, 2/12 (16.6%) C. albicans, 1 (8.3%) C. tropicalis and 1 (8.3%) C.famata, and Trichosporum spp for 2/434 (0.4%). A higher frequency of FE was observed in patients who had previously been submitted to cardiovascular surgery (8/12, 66.7% vs 162/421, 38.5%, p = 0.07). Patients with FE often acquired the infection in hospital (7/12, 58.3% vs 105/422, 24.9%, p = 0.016). Vascular embolic events were more frequent in FE (9/12, 75% vs 196/412, 47.6%, p = 0.079). Specifically, peripheral embolization (3/12, 25% vs 35/421, 8.3%, p = 0.079) and mycotic aneurisms (4/12, 33,3% vs 43/420, 10.2%, p = 0.032). A higher rate of mortality was observed in patients with Fungal Endocarditis (6/12, 50% vs 103/413, 24.9%, p = 0.05). There was no difference between the rates of surgical indication (91.7% vs 86%) and performed surgery (63.6% vs 80.3%). Discussion: The incidence of FE within the cohort of IE in adults was similar to studies published by other centres (2 to 4%). Non-albicans candida predominated (91.7%), especially C.parapsilosis, which differs from international studies but is similar to other centres in South America. This is probably related to hospital acquisition and the affinity of parapsilosis to catheters and prosthetic material. In fact, previous heart surgery and nosocomial IE were more frequent in FE. Emboli, particularly manifested as mycotic aneurisms, and peripheral emboli were two common complications of FE, which highlights the strong emboligenic dissemination of these agents. Mortality was higher in FE, at 50%, which is similar to the published literature. 110908 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Comparison of Features of S.Aureus Endocarditis to Non-S.Aureus Endocarditis in a Cardiac Referral Center in Brazil NICOLAS DE ALBUQUERQUE PEREIRA FEIJOO1, Thatyane Veloso de Paula Amaral de Almeida1, Mariana Giorgi Barroso de Carvalho1, Ingrid Paiva Duarte1, Leo Rodrigo Abrahao dos Santos1, Rafael Quaresma Garrido2, Giovanna Ferraiuoli Barbosa2, Clara Weksler2, Wilma Felix Golebiovski2, Bruno Zappa2, Marcelo Goulart Correia2, Cristiane C. Lamas2 (1) Unigranrio/Afya, Rio de Janeiro, Brasil; (2) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (3) Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brasil Introduction/Objectives: S.aureus has become the mostly encountered pathogen in series of patients with infective endocarditis (IE) from developed countries in recent years, but its role and behaviour is not so well defined in developing countries. S.aureus IE (SAIE) is described as more severe and lethal. Our aim was to describe cases of SAIE in a developing country and compare it to other cases of IE in a cohort presenting to a cardiac surgical referral center. Materials and methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Patients were identified prospectively. Categorical variables were presented as frequencies and percentages, and the SAIE group was compared to the other patients with IE in the cohort by test of proportions. A p-value less than 0.05 was considered statistically significant. Results: S.aureus accounted for 49/434(11.3%) episodes of IE. Resistance to methicillin was seen in 8/49(16.3%) strains (5 MRSA, 3 community-acquired MRSA or ca-MRSA). Patients with SAIE more often had chronic renal failure (15/49, 30.6% vs 76/384, 19.8%, p = 0.08). Rheumatic valve disease (RVD) was less often seen in SAIE (16.3% vs 33.5%, p = 0.015). Patients with SAIE more often had hospital-acquired IE (46.9% vs 23.1%, p < .001), and devices were more often affected (24.5% vs 5.5%, p < 0.001). No differences were seen regarding the frequency of paravalvular abscess (18.4% vs 15.1%), valve perforation (14.3% vs 18.8%) or fistulae (4.1% vs 4.2%). Complications more often found in SAIE were persistent bacteremia (23.9% vs 5.6%, p < .001), peripheral emboli (18.8% vs 7.5%, p = 0.01) and recurrent emboli (19.1% vs 5.1%, p < .001). Acute renal failure 44.7% vs 32.5%, p = 0.097) and need for hemodialysis (52.2% vs 25.0%, p = 0.008) were more often seen in SAIE. Rates of surgical indication (83.3% vs 86.5%), surgery (72.7% vs 80.7%) and mortality (28.6% vs 25.3%) were similar between groups. Discussion: S.aureus was the third mostly encountered causative agent in IE in our center, and was mostly associated with healthcare acquisition and intracardiac devices. Surgical rates and mortality were similar to other IE, possibly because of referral bias, but recurrent emboli, persistent bacteremia and acute renal failure were more frequent in SAIE, highlighting its acute presentation with sepsis. 110914 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Cardiovascular Risk in the Municipality of Serta CATARINA RAQUEL GASPAR DOS SANTOS1, Catarina Santos1, Patricia Coelho1, Francisco Rodrigues1 (1) Instituto Politecnico de Castelo Branco Arterial hypertension (HTA) is one of the main risk factors for cerebrovascular diseases, representing a high incidence rate in the world population. In this way, it becomes increasingly important to make people aware of the importance of hypertension and the risk factors that it entails. As such, the objective of this investigation was to assess the prevalence of hypertension in the municipality of Serta. The present research study is of the prospective type. The sample collection was based on the cluster method, through the random selection of streets in the municipality of Serta. Anthropometric data were collected, 3 blood pressure assessments were performed, with an interval of 3 minutes between each, and a survey on risk factors was applied. Statistical treatment and data analysis were performed using the SPSS Statistics program. The sample is composed of 1000 individuals, of legal age and residing in the municipality under study, with 515 (52%) of the participants being male and 485 (48%) females. The mean age was between 56.04 years. Regarding the prevalence of arterial hypertension, a percentage of 43.6% was found, and this result includes all individuals who presented mean SBP and/or DBP values above normal values (140/90 mmHg, respectively) and all individuals who take antihypertensive medication. About individuals who reported performing associated therapy, 165 individuals (60.2%) had controlled hypertension, however, 109 (39.8%) had uncontrolled hypertension. Regarding risk factors, the most affluent were obesity (61.7%), physical inactivity (48.2%) and family history of hypertension (42.3%). It is concluded that the present study found that there is a significant prevalence of hypertensive patients in this region, which may be related to the lack of control of risk factors. 110920 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Analysis of the Effects of Antidepressive Agents on Blood Pressure: A Systematic Review GABRIELA DANTAS MACHADO LEAL1, Fernanda Dantas Machado Leal1, Marilia Menezes Gusmao1 (1) Escola Bahiana de Medicina e Saude Publica Introduction: The prevalence of depression and the use of antidepressive agents have been increasing worldwide over the last few years. Hypertension is another clincal condition of high prevelence in which it is common to be associated with drepression. Objective: Avaluate by a systematic review, the likelihood of antidepressive agents effecting blood pressure, the study will also evaluate what are the classes of antidepressive agents that are related to the deacrease or increase of blood pressure value. Methods and materials: searches were conducted in databases such as PubMed and Scielo, and selected papers in humans, which included the use of antidepressive agents for depression treatment and blood pressure mesurement. Researches that have used other medications that were not antihipertensive agents, but could have potentially altered blood pressure measurement, were excluded. The review protocol was registeres in PROSPERO. The protocol registration number is CRD42020194118. Results: The final sample consisted of seven articles. In three of them, the use of antidepressive agents did not cause significant changes on the value of blood pressure. One study detected blood pressure drop after the use of antidepressive agents. While three other studies detected blood pressure spike after the use of antidepressive agents. Conclusion: Selective serotonin reuptake inhibitors (SSRIs) e serotonina and norepinephrine reuptake inhibitors (SNRIs) are not capable of influencing and altering blood pressure value, however, GSK372475 is capable of increase blood pressure value. 111006 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Comprehensive Echocardiographic Assessment with Global Longitudinal Strain in a Cohort of On-Treatment Acromegalic Patients CAROLINA MENDES PEREIRA1, Camila Pereira de Carvalho2, Clara Alice Lima Leal1, Luis Augusto Oliveira Santos1, Breno Carvalho Cirne de Simas1, Ferdinand Gilbert Saraiva da Silva Maia1, Josivan Gomes de Lima1, Lucia Helena Coelho Nobrega2, Ricardo Luiz de Medeiros Lima2 (1) Federal University of Rio Grande do Norte; (2) University Hospital Onofre Lopes Introduction: Acromegaly is a rare disease characterized by high levels of growth hormone (GH) and insulin-like growth factor (IGF-1). Cardiovascular disease, especially heart failure, is a common complication in acromegaly. Objectives: Perform a comprehensive echocardiographic assessment of acromegalic patients and relate systolic function indexes with disease activity. Methods: Bidimensional echocardiographic assessment of left ventricular geometry, Ejection Fraction (EF, determined by Simpson's method), Global Longitudinal Strain (GLS, using speckle-tracking technique) and diastolic function were performed in on-treatment acromegalic patients without established cardiovascular disease. Patients with poor acoustic window, atrial fibrillation and oncologic treatment (systemic chemotherapy or thoracic radiotherapy) were excluded. Ejection fraction and GLS were compared in patients with active and remitting disease. Results: 28 acromegalic patients were included (17 women and 11 men; mean age 42,8 +- 11,5 years; mean time from diagnosis 7 +- 4.9 years). Thirteen patients were in biochemical remission, 11 had active disease and 4 had elevated GH level with normal IGF-1 (indeterminate pattern). Structural and/or functional cardiac alterations were present in 16 patients (57.8%). Eleven patients (39.28%) exhibited abnormal geometry (7 with eccentric hypertrophy, 3 with concentric hypertrophy and 1 with concentric remodeling). Mean EF was 58.8% (+-6.3). Only one patient had mildly reduced EF. Mean GLS was 20.5 +- 2.8. Seven patients (25%) had below normal GLS (6 patients had borderline and 1 had reduced GLS). Four patients (14.28%) presented alteration in diastolic function indexes (2 with type 1 and 2 with indeterminate diastolic dysfunction). EF (57.4 +- 7.39 vs 59.5 +- 6.2, p = 0.44) and GLS (19.8 +- 3.1 vs 20.4 +- 2.7, p -0.60) were not different in patients with active or remitting disease. Conclusions: In this cohort of on-treatment acromegalic patients without established cardiovascular disease, structural and/or functional echocardiographic alterations were frequent. Left ventricular hypertrophy is the most frequent alteration. Ejection fraction and global longitudinal strain were not different in patients with active or remitting disease. 110923 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Ring Shaped Neutrophils from Peripheral Blood of Patients with Chagas Disease:Correlations with Echocardiogram Parameters LUANN GABRIEL PORPINO SALES1, Pedro Felipe Alves de Souza1, Felipe Alves de Lima1, Marcelo Augusto Araujo De Castro1, Henrique Rangelly Gabriel de Melo1, Leonardo Lacerda do Amaral1, Rafaela Germana Cavalcanti da Nobrega2, Micassio Fernandes de Andrade1, Amanda Estevam Carvalho1, Valeria Duarte de Almeida1, Cleber Mesquita Andrade1 (1) Universidade do Estado do Rio Grande do Norte (UERN); (2) Centro Universitario de Joao Pessoa (UNIPE) Introduction: Neutrophils are cells with a typical polylobulated nucleus, capable of modulating the immune response in Chagas disease (CD). In some occasions, these cells may have a ring shaped nucleus, typical of immature leukocytes with different performing mechanisms, and your greater incidence be associated with solid tumor cancers and CD. Objective: Evaluate the morphology of the peripheral blood neutrophils nucleus of patients with Chagas disease, in the different clinical forms of the disease. Methods: Transversal study with non-probabilistic sampling. A total of 32 volunteers participated in the research, being 11 individuals with indeterminate clinical form of the disease and 21 individuals with cardiac clinical form. The analysis of the morphology of the nucleus of the polymorphonuclear cells were performed by light microscopy. The identification of the clinical forms and the analysis of the echocardiogram were performed by analyzing the filed medical records. Spearman and Pearson tests were used to determine the correlations between the absolute number of ring neutrophils and echocardiographic parameters. Results: A negative correlation was observed between the absolute number of ring neutrophils in the patients' peripheral blood and the left ventricular (LV) ejection fraction (*p = 0.0031 and r = -0.7087). However, regarding the other echocardiographic parameters of LV Systolic Diameter (*p = 0.0009 and r = 0.8040), LV Diastolic Diameter (*p = 0.0250 and r = 0.5942) and Mass Index of the LV (*p = 0.0351 and r = 0.5655), a positive correlation was noticed concerning the absolute number of annular neutrophils. Conclusion: Ring shaped neutrophils from patients with CD may contribute to the physiopathology of Chronic Chagas Heart Disease. 110948 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Study Prev.Cardio.Cv - Ilha De Santiago KELLY ANNY FERNANDES MASCARENHAS1, Patricia Coelho1, Francisco Rodrigues1, Julio Rodrigues2 (1) Instituto Politecnico de Castelo Branco; (2) Ministerio de Saude Cabo Verde Introduction: Cerebrocardiovascular diseases represent a meaningful death rate worldwide, making a big challenge to public health and the economy. Many African countries like Cabo Verde are facing an epidemiologic transition from transmitted diseases to non-transmitted diseases, demographic changes as well as socio-economic changes, and are facing rapid growth in terms of cardiovascular diseases and are linked to rising in cardiovascular risk. Objectives: This present study had as its objective to identify the prevalence of risk factors of cardiovascular diseases in adults residing on the island of Santiago-Cabo Verde. Methodology: The transversal study of a population background of individuals over 18 years of age, from both genders. The data collection took place in October and November 2021, in the nine municipalities of Santiago Verde. It was excluded from the study the individuals of Cape Verdean nationality who have been living for over a year abroad and that have just arrived on Santiago Island in less than 30 days, as well as the individuals with any kind of disabilities that may affect their participation in the study. The sample size was calculated based on the population projection of the year of Santiago Island, for those over 18 years of age according to the appropriate epidemiologic sample. The field data (domiciliary) were obtained through a questionnaire application where ages, sex, race, weight, height, risk factors, (diabetes presence, dyslipidaemias, hereditariness, physical exercise practices, smoking habits, cerebrovascular antecedent events, weight control habits, and blood pressure) are considered. Results: The sample of the study is mostly made of females representing 54.8%. Furthermore, the age group with the highest sample number was between 18-27 years old, corresponding to (21%). 42.2% with BMI >= 25 kg/m2; 65.1% of physical inactivity; 7.3% with Tabaco, 14.4% with alcohol, 6.5% with cardiac diagnosed diseases, 19.9% with close family with cardiac pathology, 2.7% have had cerebral vascular, 0.1 has already suffered an ischemic transitory accident, 0.5% myocardial infarction, and 23.5% had a periodic habit of checking the blood pressure, 32.6% hypertensives and 4.5% of diabetics. Conclusion: The result of the study allowed us to affirm that there's a high prevalence of risk factors for cerebrovascular accidents in the island of Santiago-Cabo Verde, especially among women. 110988 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Late Prosthetic Valve Endocarditis in a Cohort of Adults in a Quaternary Surgical Referral Center in Brazil THATYANE VELOSO DE PAULA AMARAL DE ALMEIDA1, Mariana Giorgi Barroso de Carvalho1, Nicolas de Albuquerque Pereira Feijoo1, Ingrid Paiva Duarte1, Leo Rodrigo Abrahao dos Santos1, Rafael Quaresma Garrido2, Giovanna Ferraiuoli Barbosa2, Clara Weksler2, Wilma Golebiovski2, BRUNO ZAPPA2, Marcelo Goulart Correia2, Cristiane C. Lamas3 (1) Unigranrio/Afya, Rio de Janeiro, Brasil; (2) Instituto Nacional de Cardiologia, Rio de Janeiro, Brasil; (3) Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brasil Introduction: Prosthetic valve infective endocarditis (IE) has high morbidity and mortality. Late prosthetic valve IE (LPVE), defined as that acquired 12 or more months after prosthesis implantation, often has as causative agents' community pathogens. Our objective was to describe cases of LPVE and compare them to other cases of IE. Methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Statistical analysis was performed using the Jamovi and R software. Results: Of the 435 patients with IE, 77 (17.7%) had LPVE. They were older, with a median age of 52 years (IQR 38-68), compared to 47 years (IQR 32-61). Enterococci were more frequent in LPVE (29.2% vs 16.3%, p = 0.027), but negative blood cultures were less frequent (11.9% vs 20.3%, p = 0.036). In LPVE, infection was community-acquired in 75.3%, and hospital-acquired (HA) in 16.9%. Patients with LPVE more often had a history of coronary artery disease (21.1% vs 12.5%, p = 0.051), coronary artery bypass surgery (12.2% vs 4.5%, p = 0.01), congestive heart failure (59.2% vs 35.9%, p < 0.001), and cerebrovascular disease (17.1% vs 4.5%, p < 0.001); chronic renal failure was less frequent in LPVE (11.7% vs 23.0%, p = 0.027). Rheumatic valvular heart disease (RVD) was observed more frequently in LPVE (57.9% vs 25.7%, p < 0.001). Aortic and mitral involvement was frequent in both groups. The frequency of abscess (23.7% vs 13.7%, p = 0.029) and conduction disturbances (25.7% vs 11.2% p = 0.001) was higher in LPVE. Heart failure secondary to acute valve regurgitation was equally frequent (56.6% vs. 61.6%), as were neurological events (40.5% vs. 50.0%), including mycotic aneurysms (6.5% vs 11.8%). Splenic emboli were frequent in both groups (32.5% vs. 35.8%). Surgical indication occurred less frequently (78.9% vs 87.7%, p = 0.046), as well as surgery (67.2% vs 82.4%, p = 0.005). In-hospital death was higher in LPVE (39.5% vs 22.6%, p = 0.002). Conclusion: LPVE had a frequency of 17.7%, like other series in the literature (10-30%). However, it showed a high prevalence of VHD, as in other developing countries where it is the main reason for valve replacement. Clinical features were like other IE, except for the presence of abscesses, and mortality was very high, possibly due to patients being older, having more underlying illnesses and less often having valve replacement surgery for IE. 110991 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES The Prognostic Value of the Electrocardiogram in Chagas Disease Serology Evolution GUILHERME DANTAS CAMPOS PINTO1, Silvia Marinho Martins2, Cristina de Fatima Velloso Carrazzone2, Maria das Neves Dantas da Silveira Barros1, Carolina de Araujo Medeiros2, Gabriela Arcoverde Wanderley1, Gustavo Sales Santa Cruz1, Gabrielly Nascimento de Lima1, Virginia Maria Barros de Lorena3, Luciane de Freitas Firmino3, Maria da Gloria Aureliano de Melo Cavalcanti2, Wilson Alves de Oliveira Junior2 (1) Universidade de Pernambuco (UPE); (2) Ambulatorio de Doenca de Chagas e Insuficiencia Cardiaca - PROCAPE/UPE; (3) Fundacao Oswaldo Cruz (Fiocruz) Introduction: Changes in the electrocardiogram (ECG) are markers of severity and prognosis in chronic Chagas disease (CD). However, in the acute form, the prognostic value of the ECG before and after treatment with benznidazole, as a tool to analyze serological evolution, has not been well established yet. Objective: To verify the association between electrocardiographic changes and serology evolution in patients with acute CD. Methodology: This is a cohort study with 25 patients infected by T. cruzi in an outbreak in a city in the Brazilian Northeast. The population was followed up at a referral outpatient clinic in Pernambuco State, from acute phase treatment until 24 months (+/- 6) after benznidazole administration. The diagnosis was confirmed by serological methods and/or molecular tests. ECGs and serological tests were performed before and after treatment. Then, the remission, maintenance, and appearance of electrocardiographic changes were determined, as well as the serological evolution of each patient. The ECGs were evaluated by two professionals - one of whom is an expert in the area. P-value < 0.05 indicates a statistically significant association. Results: The population was mostly female (56%), with a mean age of 30 years (SD = 11.5) and without comorbidities (92%). The prevalence of ECG changes after 30 and 60 days of the infection was 56%. They were: altered cardiac repolarization (ACR) (20%), electrical axis deviation (20%), low QRS voltage (20%), incomplete right bundle branch block (IRBBB) (8%), left anterior fascicular block (LAFB) (8%) and first-degree atrioventricular block (8%). On reassessment of the ECGs after 2 years, 48% had some alteration: low QRS voltage (32%), IRBBB (12%), LAFB (8%), left anterior fascicular block (8%), and chaotic atrial rhythm (8%). When follow-up ECG was compared to pretreatment exam, 7 remained normal; 5 remained altered; 6 which were previously altered were normalized, and 7 presented some new alteration. Fifteen patients (60%) showed positive IgG for T. cruzi. In the acute phase, 100% of patients who had ACR before treatment had positive serology tests after 2 years (p = 0,061). There was no statistical association between serology results and the follow-up ECG. Conclusions: ECG changes in the acute phase showed no power of association with post-treatment CD serology. It is considered relevant to elucidate the predictive value of ACR in the acute phase for seroconversion, through novel studies. 111000 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Prognostic Value of Brain Natriuretic Peptide in Patients with Chagas Cardiomyopathy from Endemic Areas: Sami-Trop Cohort Study ADMILSON LEMOS DA COSTA FILHO1, Marcelo Alves Maia2, Ester Cerdeira Sabino3, Ana Isabel Nobre Maia4, Artur Lima Sendin1, Kassia Burini1, Fellipe Colares P G Versiani4, Antonio Luiz P Ribeiro2, Maria Carmo P Nunes2 (1) School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.; (2) Post Graduation Program in Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.; (3) Instituto de Medicina Tropical e Departamento de Molestias Infecciosas e Parasitarias da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.; (4) Health Science Program, Universidade Estadual de Montes Claros, Montes Claros, Brazil. Background: Chagas cardiomyopathy is an important cause of heart failure in endemic areas. Natriuretic peptides are well established in the diagnostic of heart failure, but their prognostic value is not well defined, especially in community-based Chagas patients. Objective: This study aims to assess the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting mortality in patients with Chagas cardiomyopathy from remote areas. Methods: Patients with Chagas disease from endemic areas who had heart failure defined as left ventricular ejection fraction (LVEF) <50% and/or NT-ProBNP >300 pg/ml were eligible for the study. Clinical data were obtained using a standardized questionnaire. A resting 12-lead electrocardiogram was recorded at baseline. A range of readily obtained echocardiographic measures were collected using portable equipment at public health primary centers. The end point was all-cause mortality. Results: The study cohort consisted of 370 patients with a mean age of 66.2 +- 12.7 years, and 210 patients (57%) were women. The majority of the patients had left ventricular (LV) systolic dysfunction with mean ejection fraction of 41 +- 12%. During a mean follow-up of 31 months, 133 patients died (36%) with overall mortality incidence rate of 39.6 deaths per 100 patient-years. Four key echocardiographic parameters were predictors of mortality, including LVEF (HR 0.97, 95% CI 0.95 to 0.98), right ventricular (RV) end-diastolic area (HR 1.06, 95% CI 1.03 to 1.09), E/e' ratio (HR 1.03, 95% CI: 1.01 to 1.05), and left atrial (LA) volume (HR 1.01, 95% CI 1.00 to 1.01). The inclusion of NT-ProBNP on top of echocardiographic parameters resulted in significant improvement in model performance. Conclusions: In a contemporary cohort of patients with Chagas cardiomyopathy, NT-proBNP was a strong predictor of death, independently of LV dysfunction severity and RV involvement. NT-proBNP assessment may be used in a clinical setting to improve the risk prediction model for mortality in patients with Chagas cardiomyopathy. 111010 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Consensus and Disparities Regarding Clinical Protocols for Cardiogenic Shock: A Systematic Review THIAGO FONSECA DE AZEVEDO1, Adria Rayane Lima Cascaes1, Leonardo Rodrigues Ferreira Diogo1, Pablo Rodrigues Nunes de Souza1 (1) Universidade do Estado do Para (UEPA) Introduction: In the research about cardiac pathologies, cardiogenic shock (CS) stands out, given its complexity and high incidence (between 5 and 15% of patients with acute myocardial infarction). In general, CS is the inability of the heart to perform a tolerable cardiac output to oxygenate and nourish tissues. In this sense, understanding the processes of this cardiological condition is important, as there is still a high mortality associated with it (about 50%). Despite this, it is observed that the treatment of cardiogenic shock is not standardized and doubts persist regarding its therapeutic protocol. Therefore, it is important to understand the therapeutic methods associated with cardiogenic shock, in order to manifest a logical and temporal framework in the progression of the disease and in the improvement or worsening of the patient. Objective: To assess the most used clinical treatment protocols for cardiogenic shock. Methods: Systematic review without meta-analysis, using the descriptors "Clinical protocol" and "Cardiogenic shock". The search was carried out in the PubMed, LILACS and Cochrane databases. As inclusion criteria, articles in English limited to the last five years (2018-2022) were accepted. Studies such as randomized clinical trials, cohort, case-control and observational studies were selected. Articles without abstract or full text available and duplicates were excluded. Results: Critical analysis of the collected data revealed the absence of a standardized protocol for CS across centers, together with a high post-discharge mortality despite advances in the field; however, some factors, such as early invasive hemodynamics and percutaneous coronary intervention, as well as shock team-based protocols, were correlated with higher rates of survival and better prognosis, while the use of intra-aortic balloon pump didn't show advantages in several studies, and is accordingly not recommended anymore for management of CS. Conclusion: The present study concludes that ECMO, Inotropic Agents, Impella 5.0 and percutaneous hemodynamic support were prevalent in the studies analyzed. In Addition, intra-aortic balloon pump and the creation of a Shock Team were used as a way to improve prognosis in patients with cardiogenic shock. The disparity of results showed the necessity of clinical trials and a clearer Cardiogenic Shock clinical protocol in order to establish a better CS clinical management. 111002 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Postural Orthostatic Tachycardia Syndrome: A Challenging Diagnosis EDUARDO AUGUSTO QUIDUTE ARRAIS ROCHA1, Marcela Sobreira Kubrusly1, Luis Gustavo Bastos Pinho3, Vera Marques4, Francisca Tatiana Moreira Pereira4, Bruna Sobreira Kubrusly3, Davi Sales Pereira Gondim2, Fernanda Pimentel Arraes Maia3, Rodrigo Carvalho Paiva1, Maria Eduarda Quidute Arrais Rocha2, Arnobio Dias da Ponte Filho4, Roberto Lima Farias3 (1) Centro Universitario Christus (Unichristus); (2) Universidade de Fortaleza (Unifor); (3) Universidade Federal do Ceara (UFC); (4) Centro de Arritmia do Ceara (CACE) Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) represents one form of clinical presentation among neurally mediated syndromes, with several peculiar characteristics. Many aspects of this syndrome still remain unknown. This study aimed to analyze the characteristics of patients with clinical suspicion of POTS. Methods: Retrospective cohort study, conducted in the period 2016-22. Statistical analysis was performed in the stats models module. To obtain odds ratios, we used logistic regression models (for positivity as a response) and multinomial logistic regression models (for the type of response). Other comparisons were made using the Mann-Whitney test and Fisher's exact test, with p-value of 5% considered significant. Results: The mean age for the 36 patients with a POTS response was 35.3 +- 0.45 years; 72.2% (26) were male. Among the symptoms that motivated the TT, in the POTS group, we had 69.4% (25) with syncope, 8.3% (3) presyncope, 8.3% (3) with a previous suspicion of POTS, 8.3% (3) with dizziness and 5.5% (2) unknown. None of the patients had associated pathology or reported previous medication use. The complication rate was 2.7% (1). The total number of tilt tests performed were 2462, with 115 exclusions, 37.5% of which were male, with a median age of 51.1 (31-71) years, with 66.31% TT with normal response and 33.69% positive TT. The types of response were 16.22% (377) hypotensive, 11.7% (272) mixed, 2.49% (58) dysautonomic, 1.55% (36) POTS, 1.11% (26) cardioinhibitory, 0.47% (11) psychogenic. A total of 14 patients had a previous suspicion of POTS, with 42.8% (6) presenting a positive TT, while 57.1% (8) a negative one. In the group that did not have a suspicion of POTS, the values were, respectively, 32.7% (756) and 67.2% (1554) (p = 0.47). The symptom reproduction rate in patients with a POTS response was 52.7% (19) versus 47.2% (17). Conclusion: The Postural Orthostatic Tachycardia Syndrome represented a small percentage of the TT exams performed, predominating in young patients, with a positive response on the TT, even in the absence of clinical suspicion, with reproduction of symptoms in most cases and a low rate of complications in the exam. POTS is usually a challenging diagnosis. 111057 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Inflammatory Dynamics in Brazilian Indigenous People with and Without Arterial Hypertension: A Multivariate Network Approach in the Project of Atherosclerosis Among Indigenous Populations (PAI) MANOEL PEREIRA GUIMARAES1, Carlos Dornels Freire de Souza1, Rodrigo Feliciano do Carmo1, Ricardo Khouri2, Savio Luiz Pereira Nunes3, Jandir Mendonca Nicacio1, Ana Marice Teixeira Ladeia4, Joao Augusto Costa Lima5, Anderson da Costa Armstrong1, Manoel Barral-Netto2 (1) Universidade Federal do Vale do Sao Francisco (UNIVASF); (2) Instituto Goncalo Moniz/FIOCRUZ; (3) Universidade de Pernambuco (UPE); (4) Escola Bahiana de Medicina e Saude Publica; (5) Johns Hopkins University Introduction: Atherosclerotic disease and its risk factors show relationships with inflammatory changes. The inflammatory mediation of cardiovascular risk in indigenous groups undergoing a rapid process of urbanization is still unknown. Objective: To describe the inflammatory dynamics of two indigenous groups in Northeast Brazil with and without arterial hypertension. Methods: Cross-sectional ancillary study (2016-2017) involving 302 indigenous people from the Fulnio (n = 210) and Truka (n = 92) ethnic groups (Pernambuco, Brazil). Sociodemographic data and samples of blood to measure the inflammatory markers IL-8, MPO, Tenascin-C2, Trail, FGF-2 and Lox-1. For the analysis, multivariate network analysis was used by the Leats absolute shrinkage and selector operator (LASSO)- with non-parametric transformation. This project is part of the PAI-Study (Integral Indigenous Care Project). Results: The prevalence of arterial hypertension was 23.5%. (n = 71) [20.0% in Fulnio and 31.5% in Truka] in hypertensive patients, a positive correlation was observed between Tenascin-C2 and FGF-2, which was not present in non-hypertensive indigenous people. There is a stronger positive correlation between TRAIL and IL-8 than the obs herbed in non-hypertensive patients. On the other hand, the correlation between FGF-2 and PAI-1 was stronger in non-hypertensive individuals. Conclusions: Differences were found in the inflammatory dynamics of hypertensive and non-hypertensive indigenous people, with emphasis on the positive correlation between Tenascin-C2 and FGF-2. 111062 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Differences in Hypertension Diagnosis and Control in Public and Private Health Sectors in Northeast Brazil using Home Blood Pressure Monitoring MANOEL PEREIRA GUIMARAES1, Antonio Marconi Leandro da Silva1, Elder Gil Alves da Cruz2, Matheus Pereira Barreira1, Everardo Joaquim Goncalves dos Santos1, Frank Land Carvalho1, Fernando Marcos Franca3, Audes Diogenes de Magalhaes Feitosa4, Rodrigo Feliciano do Carmo1, Jeova Cordeiro de Morais Junior1, Carlos Dornels Freire de Souza1, Anderson da Costa Armstrong1 (1) Universidade Federal do Vale do Sao Francisco (UNIVASF); (2) Clinica do Coracao Dr. Elder Gil; (3) CARDIOVASF - Instituto do Coracao do Vale do Sao Francisco; (4) Universidade Federal de Pernambuco (UPE) Introduction: Validated home blood pressure monitoring (HBPM) is not widely available in Brazil. In the places HBPM is available, it is unknown how Brazilian inequalities in access to health may impact on hypertension diagnosis and control. Objectives: To compare hypertension diagnosis and control in public and private health sectors in an unfavored outland area in Northeast Brazil (Sertao; Pernambuco). Methods: Longitudinal, multicenter study. Information on sex, age, body mass index (BMI), antihypertensive medications, office BP and HBPM was collected using the TeleMRPA platform, between September 2017 and February 2022. All equipment was validated and calibrated. All participants were classified according to the Brazilian Guidelines on Hypertension and grouped following the health sector (public vs. private). Data was also collected in recurrent exams up to six months. For data analysis, the Shapiro-Wilk, Mann-Whitney and chi-square tests were used. Results: 2,261 individuals were included. People from the public sector were younger (58.3 +- 15.7 vs 55.5 +- 15.2 years; p = 0.001), had higher BMI (29.6 +- 5.8 vs 28.1 +- 5.2 g/m2; p < 0.001), and used higher number of BP pills (1.6 +- 1.3 vs 0.9 +- 1.0 pill; p < 0.001). Male participants were more prevalent in the private sector (37.2%vs31.4%; p = 0.019). In the first HBPM performed, 54.9% of the public sector group had BP out of control, compared to 44.0% (p < 0.001) in the private sector. During follow-up, 50 participants enrolled in the new HBPM within six months of the first exam. For the second HMBP, 47.1% of the public sector group had BP out of control compared to 54.5% of the private sector (p = 0.616). Conclusion: Hypertensive participants enrolled from the public health sector had a more severe disease profile in the initial assessment but were similar to those from private sector in the 6-month follow-up period, when HBPM was used. The wide use of HBPM may aid reducing inequalities in hypertension treatment in Brazil. 111103 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Prognostic Value of QRS Axis in Chronic Heart Failure with Reduced Ejection Fraction GABRIELA ARCOVERDE WANDERLEY1, Guilherme Dantas Campos Pinto1, Gustavo Sales Santa Cruz1, Felipe Jose Gomes Pereira de Lucena1, Larissa Cassiano de Araujo1, Maria da Gloria Aureliano Melo2, Maria Elisa Lucena Alves2, Maria das Neves Dantas Silveira Barros2, Wilson Alves de Oliveira Junior2, Silvia Marinho Martins Alves2 (1) Universidade de Pernambuco; (2) Casa do Paciente Portador de Doenca de Chagas e Insuficiencia Cardiaca (PROCAPE) Introduction: Heart failure is a high mortality clinical syndrome. The electrocardiogram (EKG) is an assessable exam with low cost, very useful in the evaluation of heart failure patients. The QRS axis, determined by EKG, is a possible prognostic tool. Objective: To verify the prognostic value of the QRS axis in patients with heart failure with reduced ejection fraction (HFrEF). Methodology: Cohort study with 110 patients with HFrEF (EF <=40% in a last year echocardiogram -ECHO). QRS axis was determined by the Hexaxial Reference System and was classified in: normal (-30deg to +90deg), left axis deviation (-90deg to -30deg), right axis deviation (+90deg to +180deg) and northwest axis (-90deg to -180deg). To prognostic analysis was considered: funcional class (New York Heart Association), left ventricular end-diastolic diameter (LVEDD) on ECHO and right ventricle systolic function (RVSF), evaluated by tricuspid annular plane systolic excursion on ECHO and classified in reduced RVSF and normal RVSF. P-value <0,05 indicates a statistically significant association and a 95% confidence interval was considered. Results: The population was predominantly male (58%) and brown ("pardos", 68%) with a mean age of 57 years (29-82, SD = 11,5). Low education levels were present (70% of the patients dropped out in Primary or Secondary School). The most prevalent comorbidities were overweight/obesity (67%), arterial hypertension (61%), dyslipidemia (46%) and diabetes (31%). HFrEF most frequent etiologies were Chagas Cardiomyopathy (31%), Hypertensive Heart Disease (19%) and Isquemic Heart Disease (17%). Mean ejection fraction was 29% (12-40%, SD = 6,8). Mean LVEDD was 65 mm (30-90, SD = 8,5) and 38% of the patients had reduced RVSF. About QRS axis: 48% had normal axis, 36% had left axis deviation, 10% had right axis deviation and 5,5% had the northwest axis. Neither the functional class (p = 0,174) nor LVEDD (p = 0,623) were statistically associated with QRS deviation. QRS axis deviation was associated with RVSF (p = 0,013) and patients with right axis deviation (OR = 9,5) or left axis deviation (OR = 1,3) had more chances of presenting reduced RVSF when compared with patients with normal axis. However, the northwest axis was less likely to have reduced RVSF when compared with normal axis (OR = 0,03). Conclusion: QRS axis deviation was only associated with RVSF. 111278 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY Evaluation of the use of Antihypertensive Drugs by Mothers During Pregnancy of Children with Congenital Heart Disease GEORGIA MARQUES JARDIM1, Bianca Brinques da Silva2, Guilherme Rodrigues Viana1, Carolina Guimaraes Herzog1, Eric Seiji Kanai1, Grasiele do Amaral Martins1, Carolina Andreatta Gottschall2, Egidio Junior Lorenzetti Ruggini1, Helena Guedes da Rocha1, Leticia Vieira Senger1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto ; (2) Universidade Luterana do Brasil - ULBRA Introduction: Congenital heart diseases (CHDs) are abnormalities in the structures or functions of the heart that can compromise the individual in all age groups. In this sense, they are a public health problem, since early diagnosis is crucial for patient survival. Objective: To evaluate the use of antihypertensive drugs according to their risk classification in pregnancies of fetal CHD patients. Method: The study sample consisted of 198 patients, who were consecutively evaluated during their first hospitalization in a cardiac intensive care unit. The participants were submitted to a protocol that evaluated the use of antihypertensives during their pregnancy. These were divided according to their fetal risk, following the classification proposed by the Food and Drug Administration (FDA). The data analysis considers high risk the exposure of children to drugs that have pharmacological classes D and X. Results: Of the total sample, 103 patients (52%) were male, with ages ranging from 1 to 4934 days. The interview for data collection was carried out with the patient's mother in 48.5% of cases and with both parents in 42.9%. Most of the patients are users of the brazilian national health service. The most frequently observed CHDs were ventricular septal defect (16.1%) and atrial septal defect (16.1%). Furthermore, 124 patients (62.6%) were exposed to at least one drug during pregnancy. 18 mothers (9%) reported using antihypertensive drugs during pregnancy, which included methyldopa (n = 7-3.5%), enalapril (n = 4-2%), hydrochlorothiazide (n = 3-1.5%), verapamil (n = 2-1%) and propranolol (n = 2-1%). Regarding the use of enalapril (n = 4), two pregnant women used it in the first trimester of pregnancy and two in the second. As for propranolol, one did it in the first trimester and the other in the third. According to the FDA classification, 3 cases (16.7%) were class B medications, 12 (66.7%) class C and 3 (16.6%) class D (2 cases of enalapril, in which the use was performed in the second trimester and one of propranolol, in the third trimester). Conclusion: The use of antihypertensives belonging to class D among pregnant women in our study, suggest that these exposures may have relevance in the origin of CHD detected in patients later. The incidence and severity of clinical cases of CHD highlight the importance of prevention and education of health professionals as well as patients regarding the use of these medications in pregnancy. 111131 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Impact of the SARS-COV-2 Pandemic on Morbimortality from Heart Failure: The Northeastern Brazil Scenario CAROLINE LINK1, Ana Flavia Botelho1, Francielle Nocera Viechineski1, Bruna Kara1, Ana Carla Dlugosz1, Alice Magro Koscianski1, Camilla Mattia Calixto1, Larissa Almeida Busnello1, Paola Goncalves Moreira de Oliveira1, Julia Henneberg Hessman1, Mario Claudio Soares Sturzeneker1 (1) Universidade Estadual de Ponta Grossa - UEPG Introduction: Heart failure (HF) remains poorly prognostic and has a high morbidity and mortality rate. The SARS-CoV-2 pandemic may have influenced these parameters mainly due to the overload of health services, although regional characteristics may have been influential. Objective: To assess the impact of the SARS-CoV-2 pandemic on HF morbidity and mortality in Northeast Brazil through the analysis of DATASUS data. Method: The average hospital stay, the number (No) of hospitalizations and deaths, and the mortality rate (calculated by dividing the number of deaths by the number of hospitalizations) were evaluated from 02/2017 to 12/2021. The respective period was subdivided into pre-pandemic (02/2017 to 02/2020), pandemic (03/2020 to 06/2021), peak (12/2020 to 05/2021), first and second trimester of the peak (12/2020 to 02/2021 and 03/2021 to 05/2021) and mass vaccination (06/2021 to 12/2021). The subdivisions of the total period evaluated, named pre-pandemic and mass vaccination, were compared with the others, and the results were expressed as a percentage. Results: Compared to the pre-pandemic period, there was a reduction of approximately 33% in the pandemic period and 15% in the mass vaccination period. Compared to the peak period, there was a 50% increase in hospitalizations during the mass vaccination period. There was a reduction in the monthly average of deaths (21-28%) in the pandemic period when compared to the pre-pandemic period, with this average being similar in the mass vaccination and pre-pandemic periods. However, there was a significant increase in the mortality rate in the pandemic period (12.45%) when compared to the pre-pandemic period (10.9%), with the highest percentage observed in the mass vaccination period (12.79%). Mean hospital stay in days was highest in the first trimester (8.5) and lowest in the second trimester of the peak (7.7) and 8.1 in the pre-pandemic period. The mortality rate was higher, and the average length of stay was lower in all periods for the female gender. Conclusions: There were relevant consequences of the SARS-CoV-2 pandemic on HF morbidity and mortality in the Northeast region of Brazil, with a lower number of hospitalizations and an increase in mortality compared to the pre-pandemic period. During the vaccination period, the increase in hospitalizations and the higher mortality rate may reflect both the difficulty in monitoring the disease in previous periods and the greater access to health services. 111146 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Comparison between Clinical and Echocardiographic Profiles of Patients with Chagasic and Non-Chagasic Heart Failure in an University Hospital ARTHUR MAROT DE PAIVA1, Ana Luisa Guedes de Franca-e-Silva1, Beatriz Caldas Goncalves1, Felipe Thome Arradi1, Gustavo Elias Gomes de Oliveira1, Daniela do Carmo Rassi1, Salvador Rassi1, Aguinaldo F. Freitas Jr1 (1) Universidade Federal de Goias - UFG Introduction: Chagas disease (CD) affects about 6 to 7 million people in Latin America with a dramatic increase in areas such as United States and Europe. Cardiomyopathy is the most frequent clinical form of chronic CD, occurring in 20% to 30% of chronically infected individuals, with heart failure (HF) being one of its main manifestations. Objective: Compare echocardiographic and clinical profile of patients diagnosed with chagasic and non-chagasic HF. Methods: Analytical cross-sectional study with outpatients treated at an University Hospital between June 2020 and February 2022. Were included patients with a previous diagnosis of HF whom underwent echocardiography in the last 5 years. For the analysis of independent samples, the student's t test was performed (5% significance). Results: A total of 91 patients were included, of which 51 have HF because of CD (CHAGAS group) and 40 have non-chagasic HF (NCE group). Of the NCE patients, 10 were ischemic etiology, 9 hypertensive, 1 post-chemotherapy, 13 idiopathic, 1 trachycardiomyopathy, 2 peripartum, 1 myocarditis, 10 valvular and 6 alcoholic. Comparing the age of the two groups, the mean of CHAGAS was 64.90 (+-10.67) and NCE (+-15.05) (p = 0.04). When analyzing the heart rate, the CHAGAS group had a mean of 64.72 (+-10.81) and the NCE 72.37 (+-12.92) (p = 0.0028). Regarding systolic blood pressure (SBP), the mean of CHAGAS group was 104.78 mmHg (+-19.99) and of NCE group was 117.60 mmHg (+-30.82) (p = 0.01). About the diastolic blood pressure (DBP), the mean of CHAGAS group was 67.74 mmHg (+-11.37) and of NCE group was 75.27 mmHg (+-21.77) (p = 0.03). Regarding the echocardiographic measurements, the mean of ejection fraction in CHAGAS group was 31.07% (+-74.16) and in NCE group was 33.64% (+-101.80) (p = 0.22), the left atrium in the CHAGAS group had an average of 43.77 mm (+-7.79) and the NCE group 42.00 mm (+-7.28) (p = 0.27). The right ventricle had an average of 29.06 mm (+-8.04) in the CHAGAS group and 25.75 mm (+-6.58) in the NCE group (p = 0.04). The mean of left ventricular mass index in CHAGAS group was 134.97(+-39.40) and in the NCE group was 142.91 (+-39.69) (p = 0.36). Conclusion: About clinical measures, there was a significant difference in the values of heart rate, SBP and DBP between the two groups, with CHAGAS showing lower values than NCE group. Among the echocardiographic measurements, the measurement of the right ventricle was the only one that showed a significant difference, with CHAGAS group showing higher values. 111139 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Tilt Table Test in the Evaluation of Syncope, Presyncope or Postural Dizziness. Analysis of a Cohort of 2462 Patients in Brazil MARIA EDUARDA QUIDUTE ARRAIS ROCHA1, Luis Gustavo Bastos Pinho2, Bruna Sobreira Kubrusly2, Roberto Lima Farias2, Vera Marques4, Arnobio Dias da Ponte Filho4, Francisca Tatiana Moreira Pereira2, Maria Jaqueline Batista2, Juvencio Santos Nobre2, Maria Camila Timbo Rocha3, Camila Pinto Cavalcante2, Eduardo Arrais Rocha2 (1) Universidade de Fortaleza (Unifor); (2) Universidade Federal do Ceara (UFC); (3) Centro Universitario Christus (UNICHRISTUS); (4) Centro de Arritmia do Ceara (CACE) Introduction: The tilt table test (TT) provides relevant information on individual susceptibility to neuro-mediated hypotension and bradycardia. Its importance has been questioned with the advent of implantable cardiac monitors. In this work, we analyzed the results and safety of the Tilt Test in the investigation of syncope, presyncope or postural dizziness in the general population. Methods: Retrospective cohort study, with analyzes of TT exams performed by 5 specialists in cardiac arrhythmias, from 2016 to 2021, in a syncope unit. Comparative analyses were performed using the Mann-Whitney tests, multiple logistic regression and ROC curves, with a p-value of 5% considered significant. The protocols used were the Westminster or Italian protocol, with a sensitization phase with 1.25 mg of sublingual isosorbide, used as assessed by the physician during the examination. Results: A total of 2462 tilt tests performed were analyzed, with 115 exclusions, 61.7% of which were female, with a median age of 51.1(31-71) years. The overall positivity rate was 33.3%, with 43.3% with pharmacological sensitization (p < 0.01). In patients with tests requested to investigate syncope, positivity was 34.2% (477) x 30.65% (285) for other symptoms, with a significant difference in relation to the overall rate (p < 0.001), while evaluating syncope and pre-syncope together, the difference was 37.55%(623) x 20.9%(139) for other symptoms (p < 0.001). Positivity rates were higher in: males (p < 0.01; OR = 1.40 (1.16-1.69)), older patients (p < 0.01; 1.01(1.009-1.02)), in the sensitized tests (p < 0.01; 2.01(1.64-2.38)), in patients with early orthostatic hypotension with symptoms (p < 0.01; 9.68 (4.13-27.44)) or without symptoms (p < 0.01; 2.93(2.07-4.18). Previous use of hypotensive drugs or the pathologies presented were not significant as predictors of response. The complication rate was 4.85%, without hospitalization or death. Conclusions: The Tilt Table Test continues to be an important and safe methodology in the investigation of patients with suspected neurally mediated syndromes in clinical practice in Brazil. 111142 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Tolerability of Beta-Blockers: Comparison between Patients with Chagasic and Non-Chagasic Heart Failure ARTHUR MAROT DE PAIVA1, Ana Luisa Guedes de Franca-e-Silva1, Beatriz Caldas Goncalves1, Felipe Thome Arradi1, Gustavo Elias Gomes de Oliveira1, Daniela do Carmo Rassi1, Salvador Rassi1, Aguinaldo F. Freitas Jr1 (1) Universidade Federal de Goias - UFG Introduction: Chagas disease (CD) is a zoonosis whose main manifestation is heart failure (HF). One of the drugs most related to a better prognosis in HF are beta-blockers. However, the use of this class in patients with heart failure because of CD may be limited due to the patient's heart rate. Objective: Compare the tolerability of beta-blockers in patients with chagasic and non-chagasic HF Methods: Analytical cross-sectional study with patients with HF who used beta-blockers in outpatient clinic of an University Hospital between June 2020 and February 2022. For the analysis of independent samples, the student's t test was performed (5% significance). Results: 78 patients were included in the study, being 27 male and 51 female. The non-chagasic etiology group (NCE) had 35 patients and the chagasic etiology group (CHAGAS) 43. Of the NCE group, 8 of them were ischemic etiology, 1 valvular, 6 alcoholic, 8 hypertensive, 1 post-chemotherapy, 6 idiopathic, 2 peripartum and 1 myocarditis. In CHAGAS group, 33 were in use of metoprolol with a mean dose of 67 mg and 10 carvedilol with a mean dose of 6 mg. In the NCE group, 27 were in use of metoprolol with an average dose of 90 mg and 8 carvedilol with an average dose of 6 mg. In the CHAGAS group, 48% were in use of amiodarone, 4% calcium channel blockers, 25% angiotensin receptor blockers (ARB), 20% digoxin, 83% loop diuretic, 86% spironolactone, 32% ACE inhibitor, 11% SGLT-2 inhibitor and 23% sarcobitril-valsartan. In the NCE group, 17% were in use of amiodarone, 14% calcium channel blockers, 34% ARB, 11% digoxin, 71% loop diuretic, 82% spironolactone, 45% ACE inhibitors, 20% ISGLT-2 and 17% used sarcobitril -valsartan. When comparing heart rate, the NCE group had a mean of 72.94 (+-13.46) and the CHAGAS group 64.67 (+-10.59) p = 0.0033. The NCE group had a mean systolic blood pressure (SBP) of 117.8 (+-32.13) and the CHAGAS group had a mean SBP of 107.18 (+-19.82) p = 0.07. The mean NCE ejection fraction was 33.64% (+-10.09) and the CHAGAS mean was 31.07% (+-8.61) p = 0.22. Of the patients in the CHAGAS group, 6 were on a maximum dose of beta-blocker and 37 were not. In the NCE group, 9 were on the maximum dose and 26 were not, with a prevalence ratio of 0.86 (0.6-1.0). Conclusion: The CHAGAS group had a lower heart rate than NCE group. SBP of CHAGAS group showed a tendence to have lower values than NCE group. The number of patients using maximum dose of beta-blockers was lower in CHAGAS group than NCE group. 111144 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The Impact of the COVID-19 Pandemic on the Care and Mortality of Patients with Rheumatic Heart Disease in Brazil: A Comparative Study and Time Series Analysis BEATRIZ XIMENES BANDEIRA DE MORAIS1, Larissa de Oliveira Beltrao1, Luiza Dias Aguiar1, Bianca Guirra Matos de Oliveira1, Arycia Lais Nascimento Cunha1, Paloma Gomes Tavares Sette1, Michelle Lima de Carvalho Silva1, Lucas Sandes de Lima1, Renato Dias Aguiar1, Augusto Franca Cruz Ximenes2, Andreza Leite Marques de Sa Souza1, Alexandre Duram de Lima Junior3 (1) Faculdade Pernambucana de Saude (FPS); (2) Universidade Catolica de Pernambuco (UNICAP); (3) Instituto de Medicina Integral Professor Fernando Figueira (IMIP) Background: Rheumatic Heart Disease (RHD) is the major cause of morbidity and mortality from severe or multiple episodes of acute rheumatic fever (ARF), a serious public health problem, especially in low and middle-income countries. These patients need continuous cardiac care and, in severe cases, heart valve surgery. During the COVID-19 pandemic, access to these services was limited, leading to adverse clinical outcomes to many patients living with RHD. Objectives: This study aims to assess the impact of the COVID-19 pandemic on Hospital Admissions (HA), In-Hospital Morbidity and Mortality Rate from RHD in Brazil. Methods: A time-series, observational study, using the public database from the Brazilian Unified Public Health System (DATASUS), to conduct a comparative analysis of HA, Morbidity and Mortality Rate from RHD, in Brazil, in 2020 and 2021, using as reference values from 2016 to 2019, and linear regression projection for 2020 and 2021. Results: Compared to 2019, HA for RHD decreased in 31.5% in 2020 and 30.65% in 2021, In-Hospital Morbidity decreased in 19.15% in 2020 and 28.24% in 2021, In-Hospital Mortality Rate was 9.21 in 2020, a 16.43% increase, and 8.05 in 2021, a 1.77% increment. The number of valvuloplasties and valve replacement surgery fell, there was a reduction of 31.66% in 2020 and 34.64% in 2021, compared to 2019, whilst their mortality rate grew from 12.02 in 2019 to 13.59 in 2020, 13.05% increase, and was at 12.26 in 2021. All the 2020-2021 rates differed from their projected trend, specially 2020 values. Conclusion: Resource prioritization and COVID-19 contention strategies, paired with patient's reluctance to seek medical help, corroborated with precautionary postponement of elective procedures and reduction in HA and In-hospital morbidity for RHD, leading to delays in care and assistance, and a consequent increase of in-hospital mortality rates. Meanwhile, postponement of procedures implicated in the delay and decrease of valvuloplasties and heart valve replacement surgeries, leading to higher procedural mortality rates and severe consequences to the clinical outcome of RHD patients. 111161 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Cardiovascular Manifestations in Previously Healthy Individuals with COVID-19: A Sub-Analysis of Coronaheart Study GEORGIA FIGUEIREDO RAMOS1, Francis Ribeiro de Souza2, Patricia O. Guimaraes3, Renato D. Lopes4, Cicero P. Albuquerque2, Alexandre Soeiro2, Renata M. do Val2, Ludhmila A. Hajjar2, Maria Janieire de Nazare Nunes Alves2, Roberto Kalil Filho2 (1) University Santo Amaro (UNISA), Sao Paulo, SP, Brazil; (2) Heart Institute (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil; (3) Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil; (4) Duke University Medical Center - Duke Clinical Research Institute, Duke Health, Durham, United States of America; (5) Hospital Beneficencia Portuguesa Mirante, Sao Paulo, SP, Brazil; (6) Hospital Sirio Libanes, Sao Paulo, SP, Brazil Introduction: Previous studies showed that patients with prior history of cardiovascular disease present worst clinical outcomes when infected by Coronavirus Disease 2019 (COVID-19). Moreover, elevated levels of troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP), are important prognostic markers associated with poor outcomes. However, whether patients with COVID-19 without prior structural heart disease may present cardiovascular alterations are poorly understood. Objectives: We aimed to evaluate if individuals with COVID-19 without prior history of structural heart disease may present cardiovascular manifestations and/or cardiac dysfunction. In addition, we also evaluated the factors that could be associated with a worst clinical outcome. Methods: This is an unicentric, retrospective, secondary analysis of the previous study (CoronaHeart study). For this analysis, 1198 patients were assessed. However, only those patients without prior history of structural heart disease who presented alterations in echocardiogram (ECHO) at admission were included. Additionally, logistic regression models to evaluate the association between clinical variables and in-hospital mortality were performed. Results: A total of 40 participants had cardiovascular manifestations and were included (mean age 60 +- 14 years; 62% male). Overall, at hospital admission, 60% were admitted to intensive care units (ICU), and needed mechanical ventilation, 75% had elevated troponin levels, and 60% had elevated D-dimer levels. In-hospital mortality was 48%. The strongest factors associated with in-hospital mortality were elevated NT-proBNP levels (hazard ratio [HR] 1.0, 95% confidence interval [CI] 1.0-1.0 p = 0.002) and length of ICU stay (HR 0.87, 95% CI 0.77-0.98 p = 0.024). Additionally, in the hospital admission ECHO, 30% had acute pulmonary hypertension in the absence of thromboembolic events. Further analyses showed a higher rate of mortality in those individuals who presented an increased Systolic Pulmonary Artery Pressure (PAPs) compared to those individuals who presented normal values of PAPs [median, 95% CI, 44 (34-51) vs 30 (24-40) mmHg, respectively, p = 0.027]. Conclusion: Patients with COVID-19 even in the absence of prior history of structural heart disease may present cardiovascular manifestations and cardiac dysfunction associated with higher rate of mortality. Additionally, the increasing PAPs was more evident in the subjects with worst outcome. 111173 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Cardiac Autonomic Response to Isometric Exercise in Elderly Subjects with Frailty Syndrome GIULIA MICALI1, Tuany Mageste Limongi Zamperlim2, Luciana Gonzales Auad Viscardi1, Camila Martins1, Giovanna Dolder1, Pricila Helena de Souza1, Rodrigo Moreno de Oliveira1, Thamyres Oliva Bueno1, Higor Quintas Goncalves1, Leila Dal Poggetto Moreira1, Adriana Sarmento de Oliveira1 (1) UNIVERSIDADE ANHEMBI MORUMBI -UAM; (2) UNIVERSIDADE FEDERAL DE JUIZ DE FORA-UFJF Introduction: Frailty syndrome is the progressive decline of physiological systems. One of its dysfunctions is reduction of heart rate variability (HRV), which is related to adverse cardiovascular effects, a leading cause of death in the elderly. Objective: To evaluate the impact of advanced fragility syndrome on cardiac autonomic control in the elderly. Methods: In this cross-sectional prospective study, 18 Pre-Fragile (PF) and 9 Fragile (F) patients, of both genders aged over 65 years, were evaluated at Centro Integrado de Saude. Using Fried's criteria, participants were grouped as F, PF or NF if presenting with 3, <=2, or nil criteria features, respectively. Staging focused on unintentional weight loss, low level of physical activity, exhaustion, reduced walking speed, and decreased grip strength. Isometric exercise protocol was performed at 30% maximum handgrip strength with participants in supine position during a 3 minutes isometric exercise. Analyses in the time domain used heart rate indices (MNN, SDNN, RMSSD, and pNN50). Low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.49 Hz) indices in absolute (m2) and normalized (un) units and the LF/HF ratio representing the sympathovagal balance were used in frequency domain analyses. Student t-test and Mann Whitney U test were used to compare differences between two groups. Statistical significance was set at p < 0.05. Results: For time domain, there were no significant difference between groups for interval between heart beats (Mean RR; PF: 829.2 +- 61.4 vs F: 828.5 +- 85.7;p = 0.98), heart rate (Mean HR; PF: 72.8 +- 5.3 vs F: 73.4 +- 8.4;p = 0.83) and in parasympathetic modulation indices like SDNN [PF: 17.4 (13.1-19.5) vs F: 17.0 (10.0-20.1);p = 0.41], RMSSD [(PF: 17.9 (12.6-19.0) vs F: 15.6 (12.9-17.9);p = 0.41] and pNN50 [(PF: 1.6 (0.0-5.1) vs F: 0.4 (0.0-1.2);p = 0.28]. Conversely, for frequency domain parasympathetic modulation was lower in the F group compared to PF group [HFms; PF: 106.1 (56.8-165.7) vs F: 67.6 (19.8-85.6); p = 0.03]. There were no significant differences between groups for sympathetic modulation [LFms; PF: 144.8 (84.7-163.0) vs F: 86.9 (36.9-129.7); p = 0.12], LFun (PF: 56.2 +- 11.4 vs F: 63.5 +- 10.9; p = 0.11), HFun related to parasympathetic modulation (PF: 43.7 +- 11.5 vs. F: 36.4 +- 10.9; p = 0.11) and the sympathetic-vagal balance LF/HF ratio (PF: 1.5 +- 0.8 vs. F: 2.0 +- 0.9; p = 0.12). Conclusion: During exercise, fragile individuals show poorer parasympathetic modulation compared to pre-fragile elderly. 111182 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Epidemiological Profile of Hospital Morbimortality Due to Chronic Rheumatic Heart Disease in Northern Brazil from 2011 to 2021 VANDO DELGADO DE SOUZA SANTOS1, Elisama Quintino Sales1, Saul Rassy Carneiro1 (1) Universidade Federal do Para - UFPA Introduction: Chronic Rheumatic Heart Disease (RHD), associated with reduced socioeconomic development in a given country, is a sequela of rheumatic fever, which is a complication of pharyngotonsillitis caused by Streptococcus pyogenes and results from a late immune response to this infection in populations genetically predisposed. Objectives: To analyze the epidemiological profile of hospital admissions and the RHD mortality rate in the northern region of Brazil from 2011 to 2021. Methods: This is a descriptive longitudinal epidemiological study based on secondary data from the Department of Informatics of the Unified Health System regarding the number of hospitalizations, gender, age group and RHD mortality rate in northern Brazil, between January from 2011 to December 2021. Results: In the analyzed period, 3,841 hospitalizations for RHD were recorded in the northern region, with the highest number of hospitalizations in 2017 (n = 468) and the lowest in 2021 (n = 246). The state of Para had the highest rate of hospitalization for CRC (39.47%), followed by the state of Amazonas (30.82%), the state of Roraima had only 14 cases (0.36%). Females were the most affected (52.17%), the state of Amazonas was the only one with the highest rate of hospitalizations of the male population compared to females (59.97%) and the state of Tocantins was the one with the highest rate of hospitalizations females compared to males (59%), the age group most affected was 50 to 59 years (17.65%). Regarding the number of deaths, a total of 361 deaths from RHD were recorded, the year 2014 had the highest number (n = 55) and 2013 the lowest (n = 21), the state of Roraima had the highest mortality rate (21, 43%) and the state of Tocantins the lowest (9.06%). The female population had the highest mortality rates (54.02%) compared to the male population (45.98%), the most affected age group was 50 to 59 years (21.33%). Conclusion: The study showed that the states Para and Amazonas had the highest numbers of hospitalizations and deaths in the analyzed period. The low rate of hospitalizations and mortality in the most geographically distant states was noticeable, indicating an inefficiency in access to health. The data showed a higher number of hospitalizations and deaths in women and in the population over 30 years of age. With this, the impact of RHD on the health of population and the need for prevention, diagnosis and early treatment policies can be seen. 111183 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Smoking Load as a Predictor of Cardiovascular Events in 30 Days After the First Myocardial Infarction MARIA LUIZA DE CASTRO AMARAL1, Maria Luiza de Castro Amaral1, Manuella Bernardo Ferreira1, Maria Eduarda Valente da Luz Fontes1, Cecilia Meirelles Gaspar Coelho Tomazzoni1, Larissa Rovaris de Quevedo1, Roberto Leo da Silva2, Tammuz Fattah2, Daniel Medeiros Moreira2 (1) Universidade do Sul de Santa Catarina (UNISUL); (2) Instituto de Cardiologia de Santa Catarina (ICSC) Objective: This study evaluated whether there is an association between previous smoking load and the incidence of cardiovascular events 30 days after the first myocardial infarction (AMI). Methods: This is a preliminary analysis of data from the Catarina Heart Study, a prospective cohort that assesses patients diagnosed with first-time AMI. Results: There was a significant association between smokers and non-smokers age (56 +- 9.2 vs 62.0 +- 11.5) and Body Mass Index (BMI) [26.6 (23.6-29.3) vs. 27.9 (25.0-31.1)]. There was an increase in thrombosis and reinfarction (AMI) at 30 days in smokers vs. non-smokers, with an incidence (2.5% vs. 0.2%) and (3.7% vs. 0.7%), respectively. There was an association between previous smoking load to the first AMI with reinfarction [OR 1.028 (CI 1.013-1.043)] and in-stent thrombosis [OR 1.023 (CI 1.004-1.043] at 30 days among smokers. In the smoking population, there was a significant association between previous smoking load and post-infarction ventricular function evaluated with left ventricular ejection fraction (LVEF) (r = 0.093, P = 0.047). Conclusion: Patients with previous smoking load had more re-infarction and in-stent thrombosis. Smokers had better post-infarction LVEF, fitting into the smoking paradox. 111191 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Infective Endocarditis Associated with Congenital Heart Disease in a Cardiac Surgery Referral Center in Brazil MARIANA GIORGI BARROSO DE CARVALHO1, Thaissa dos Santos Monteiro2, Thatyane Veloso de Paula Amaral de Almeida1, Nicolas de Albuquerque Pereira Feijoo1, Leo Rodrigo Abrahao dos Santos1, Wilma Golebiovki2, Clara Weksler2, Giovanna Ferraiuoli Barbosa2, Bruno Zappa2, Rafael Quaresma Garrido2, Marcelo Goulart Correia2, Cristiane C. Lamas3 (1) Universidade do Grande Rio - Unigranrio; (2) Instituto Nacional de Cardiologia - INC; (3) Instituto Nacional de Doencas Infecciosas Evandro Chagas - Fiocruz Introduction: Congenital heart disease is among the several risk factors for infective endocarditis (IE) and it has distinct clinical features. Objectives: Our objective was to describe cases of IE in patients with congenital heart disease (CHDIE) in a developing country and compare it with other cases of IE in a cohort presented to a referral center for cardiac surgery. Methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Statistical analysis was performed using the Jamovi and R software. Results: There were 435 episodes of IE, of which 61 (14%) were CHDIE. Of these, 21/61(34.4%) were bicuspid aortic valves. There was no difference in the proportion of gender between CHDIE and other IE. Coronary artery disease, diabetes mellitus, systemic arterial hypertension and chronic renal failure were observed less frequently in CHDIE (3.3% vs 15.8%, p. = 0.008; 4.9% vs 13.9%, p = 0.06; 27.6% vs 51.6%, p < 0.001; 6.6% vs 23.4%, p = 0.002, respectively), but previous heart failure was frequent for both groups (39.3% vs 40.1%). Patients with CHDIE less frequently had hospital-acquired IE (14.8% vs 27.6%, p = 0.033). Aortic regurgitation was more frequent in CHDIE (51.7% vs 36.7%, p = 0.027) as were aortic vegetations (62.3% vs 38.2%, p < 0.001), while mitral regurgitation was less frequent (14.8% vs 50.7% p < 0.001). No differences were observed regarding the frequency of valve perforation (18% vs 18.3%) or fistulae (4.9% vs 4%), however paravalvular abscess was more frequent (32.8% vs 20.9% p = 0.004). The frequency of fever, embolic and immunological phenomena, splenomegaly, CRP and ESR levels were not different between groups. There was no difference in the proportion of microorganisms (S.aureus, viridans group streptococci, enterococci or fungi) identified in blood cultures. The rates of surgical indication (91.7% vs 85.3%) and surgery performed (81% vs 79.6%) were similar. Mortality was lower for CHDIE (19.3% vs 26.6%) but this was not statistically significant (p = 0.238). Conclusion: In our cohort, bicuspid aortic valves were the most frequent CHD found. There were fewer comorbidities in patients with CHDIE, and a lower mortality, possibly because it presents usually in young adults. The aortic valve was more affected, corroborating the most common malformation in congenital heart diseases, which is the bicuspid aortic valve. 111203 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Effects of Hiperdia Program on Mortality from Hypertension, Diabetes Mellitus and Cardiovascular Diseases in Bahia, Brazil DAVI FIALHO SILVA1, Davi Fialho Silva1, Fabio Leandro dos Santos Correia1, Anselmo Araujo Oliveira1, Lucas Perales Borbon1, Joao Gabriel Neves Lopes1 (1) Universidade do Estado da Bahia Introduction: Cardiovascular diseases (CVD) and Diabetes Mellitus (DM) are currently among the main challenges for Public Health in Brazil. Systemic Arterial Hypertension (SAH) is a multifactorial disease that affects the blood circulation, causing serious damage to target organs. DM is an endocrine-metabolic disease that mainly affects carbohydrate metabolism, causing systemic and target organ impairment. The proper diagnosis and treatment of these diseases, as well as an effective therapeutic adherence is essential for the patient's quality of life. Failures resulting from incorrect management demand high public expenditures. To reduce the impact of these comorbidities, the HiperDia program was created through Ordinance No. 371/2002 of the Ministry of Health. Objective: To verify the effect of the HiperDia Program on mortality from SAH, DM and CVD in Bahia. Methods: Data were obtained from the Mortality Information System database (SIM-DATASUS), and deaths related to codes I10, E10, E11, E13, E14 and chapter IX of the ICD-10 were collected. Mortality coefficients and annual percentage change rates (APC) of SAH, DM and CVD were calculated in Bahia in the period, before and after the HiperDia Program. Result: There was an increase in the median mortality rate in all the variables studied after the implementation of the program (Table 1). There was a statistically significant reduction in the growth of deaths from DM and CVD (Table 2). Conclusion: The increase in the median mortality coefficients indicates how challenging it is for the Health System to properly manage these diseases. However, there was a deceleration in the growth of mortality from CVD and DM in Bahia after Hiperdia, suggesting a possible effect of the program on mortality from these diseases. 111211 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Menopause: A Pillar for Assessing Myocardial Ischemia in Women CLEOVALDO RIBEIRO FERREIRA-JUNIOR1, Claudia Bispo Martins-Santos1, Lara Teles Alencar Duarte1, Allexa Gabriele Teixeira Feitosa1, Edvaldo Victor Gois Oliveira1, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe (UFS) Introduction: Cardiovascular disease (CVD) in women differs from CVD in men because it has sex-specific risk factors related to reproductive health and hormonal changes. In the menopausal transition phase, estrogen levels decrease, and this is a moment of acceleration of the risk of CVD, with CVD being the main cause of morbidity and mortality in postmenopausal women. According to a meta-analysis involving studies from 24 countries on 6 continents, the global mean age of menopause is 48,78 years. Objective: To evaluate menopause as an additional factor to the classic risk factors for myocardial ischemia (MI) in women undergoing Physical Stress Echocardiography (ESE). Methods: Cross-sectional study performed between January 2000 and January 2022 with women who underwent ESE at a cardiology referral service in Sergipe. A total of 7276 women (age: 58.6 +- 10.9 years) were included, divided into two categories according to the ESE result: positive or negative for MI. Patients over 48 years of age were considered menopausal women. For analysis, binary logistic regression was used to identify whether menopause and other risk factors were independently associated with MI. To enter the model, the significance level was p < 0.10 and, to remain, p < 0.05. Finally, the chi-square test was performed to assess factors associated with menopause. Results: The frequency of MI was 19.5% with a 95% confidence interval of 18.6-20.3. The factors independently associated with MI were: menopause (OR = 1.72; 95%CI 1.42-2.08), dyslipidemia (OR: 1.90; 95%CI 1.66-2.16), diabetes (OR = 1.54; 95%CI 1.30-1.82), hypertension (OR = 1.22; 95%CI 1.07-1.39) and family history (OR = 1.58; 95%CI 1.39-1.79). The group of postmenopausal women had a higher presence of comorbidities, such as hypertension (p < 0.0001), diabetes (p < 0.0001) and dyslipidemia (p < 0.0001); however, it presented better habits regarding the practice of physical activity (p = 0.002) and a lower frequency of smoking (p = 0.007). There was no difference between women before and after menopause in the distribution of obesity and family history (p > 0.05). Conclusions: Menopause is an additional factor to consider when evaluating for MI in women. The classic risk factors dyslipidemia, diabetes, hypertension and family history were also associated with MI. 111218 Modality: E-Poster Scientific Initiation - Non-case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Early Prosthetic Valve Infective Endocarditis in a Cardiology Referral Center Cohort of Adult Patients MARIANA GIORGI BARROSO DE CARVALHO1, Thatyane Veloso de Paula Amaral de Almeida1, Nicolas de Albuquerque Pereira Feijoo1, Ingrid Paiva Duarte1, Leo Rodrigo Abrahao dos Santos1, Wilma Golebiovki2, Clara Weksler2, Giovanna Ferraiuoli Barbosa2, Bruno Zappa2, Rafael Quaresma Garrido2, Marcelo Goulart Correia2, Cristiane C. Lamas3 (1) Universidade do Grande Rio - Unigranrio; (2) Instituto Nacional de Cardiologia - INC; (3) Instituto Nacional de Doencas Infecciosas Evandro Chagas - Fiocruz Introduction: Early Prosthetic Valve Infective Endocarditis (EPVIE), defined as infective endocarditis (IE) occurring up to 1 year after valve replacement surgery, is a feared complication and usually involves hospital pathogens. Our aim was to describe cases of EPVIE in a developing country and compare it with other cases of IE in our cohort. Methods: Adult patients with definite IE according to the modified Duke criteria were included from 2006-2021 using the International Collaboration in Endocarditis case report form. Statistical analysis was performed using the Jamovi and R software. Results: EPVIE was responsible for 10.8% of episodes of IE (47/435). Median age of patients with EPVIE was 54 years [34.5-64.5], significantly different to other IE, where it was 47 years [33-61.3]. No differences were found regarding gender, diabetes mellitus, chronic renal failure, congenital heart disease and rheumatic valve disease (RVD). However, patients with EPVIE more frequently had coronary artery disease (25.5% vs 12.6%, p = 0.016), coronary artery bypass graft surgery (15.2% vs 4.7% p = 0.004), heart failure (58.7% vs 37.7% p = 0.006), cerebrovascular disease (12.8% vs 5.9% p = 0.077) and arterial hypertension (69.8% vs 45.5% p = 0.003). Fever, embolic and immunological phenomena, splenomegaly, CRP and ESR levels were not different between EPVIE and other cases of IE, although the presence of new murmurs was less frequent (28.3% vs 57.8%, p < 0. 01). Most found complications in EPVIE were myocardial or paravalvular abscess (32.6% vs 21.4%, p < 0.01), acute renal failure (ARF) (48.9% vs 32%, p = 0.024) and need for hemodialysis (HD) (45.8% vs 82.4%, p < 0.01). The microorganisms most frequently associated with EPVIE were enterococci (18.8% vs 9.8%, p = 0.06) and coagulase-negative staphylococci, but not S.aureus (4.1 vs 11.7%). Surgical indication rate was 58.7% (vs 89.4%, p < .001) and surgery (56.4% vs 80.7%, p < .001) in patients with EPVIE were lower when compared to other cases of IE, while the mortality rate (31.1% vs 25%) was higher, but not statistically different between groups. Conclusions: Myocardial abscess, which is an absolute surgical indication, occurred in almost 1/3 of EPVIE. Possibly because of poor clinical status and frequent comorbidities, patients with EPVIE had less surgical indication and less surgery than the others in the cohort, evolving with high mortality. 111227 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Clinical Factors Associated with Chronotropic Incompetence in Women CLEOVALDO RIBEIRO FERREIRA-JUNIOR1, Lara Teles Alencar Duarte1, Allexa Gabriele Teixeira Feitosa1, Edvaldo Victor Gois Oliveira1, Claudia Bispo Martins-Santos1, Enaldo Vieira de Melo1, Antonio Carlos Sobral Sousa1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe (UFS) Introduction: Cardiovascular disease (CVD) has become increasingly prevalent in women, although it is underestimated when compared to other diseases specific to women. It differs from CVD in men in terms of pathophysiology, with traditional risk factors predicting higher or lower risk of CVD in women than in men. Objective: To evaluate the clinical factors associated with Chronotropic Incompetence (CI) in women undergoing Exercise Stress Echocardiography (ESE). Methods: Cross-sectional study between January 2000 and January 2022 with women who underwent ESE at a cardiology referral service in Sergipe. A total of 7049 women (age: 58.6 +- 10.9 years) were included, divided into two categories according to the chronotropic index: chronotropic competent and incompetent. Patients with a chronotropic index less than 0.8 were considered chronotropic incompetent. For analysis, binary logistic regression was used to identify factors that were independently associated with CI. Results: We compared 6430 (91.2%) competent women and 619 (8.8%) incompetent women. Dyslipidemia, diabetes, family history of CVD, obesity and beta-blocker use (withdrawn 3 days before the exam) were not independently associated with CI (p > 0.05). Factors independently associated with CI were: sedentary lifestyle (OR = 2.49; 95%CI 1.93-3.21), smoking (OR: 2.84; 95%CI 1.60-5.05), former smoking (OR = 1.90; 95%CI 1.29-2.79), age 60 years or older (OR = 1.55; 95%CI 1.24-1.95), hypertension (OR = 1,39; 95%CI 1.09-1.78) and previous presence of symptoms such as chest pain - typical or atypical - or dyspnea in the clinical history (OR = 1.45; 95%CI 1.14-1.85). Conclusions: Bad habits such as smoking and physical inactivity had the highest odds ratios for CI. Patients who did not quit smoking were more likely to have CI than former smokers. Beta-blocker discontinued 3 days before the exam was not independently associated with CI. 111658 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Number of Deaths from Ischemic Cardiovascular Diseases in Brazil: An Epidemiological Analysis BEATRIZ CUNHA LISBOA DE MEDEIROS NUNES1, Luisa Silva de Azevedo2, Julia Freitas Carneiro2, Kimberlly Aparecida de Sousa Ferreira2 (1) Universidade Potiguar - UNP; (2) Universidade Do Estado Do Rio Grande Do Norte - UERN Introduction: Chronic non-communicable diseases (CNCD) have gained space in the epidemiological and social context, constituting a global problem responsible for 74% of annual deaths. In Brazil, which follows this pattern, it is still possible to single out ischemic heart diseases (IHD) as the main cause of death in all states. To endure this reality, the Strategic Action Plan for Combating CNCD was established which was not able to achieve its goals. Objective: To analyze the number of deaths due to IHD in Brazil, from 2010 to 2020, and correlate it with the goals of the Strategic Action Plan to Combat CNCDs in force. Methods: Based on a time-series study on the number of deaths from IHD that occurred in Brazilian macro-regions, from 2010 to 2020. Data were taken from the Mortality Information System of the Informatics Department of the Unified Health System. To obtain the approach, the International Classification of Diseases was used, specifically the codes I20 to I25. Results: From 2010 to 2020, 1,208,022 total deaths from IHD were registered in Brazil, with a percentage increase of approximately 10% of the cases recorded in the studied period. Furthermore, there is an increase in the number of deaths recorded by four out of the five regions in the country, with emphasis on the North, which shows an increase of 56.13% in its percentage of deaths. In 2011, the Health Ministry of Brazil launched the Strategic Action Plan to Combat CNCD as a way to contain the rising trend predicted in 2010 for the following decades. In the opposite direction of the efforts, it can be observed, by the exposed data, that the purpose is not close to being achieved. On the contrary, the numbers in most Brazilian regions are in full advance, as can be seen in the figures in Table 1. Conclusions: IHDs still represent an important obstacle to public health in Brazil. The disparities in rates among the states reveal the need for actions consistent with the reality and local singularities. Not reaching the goals established in the plan has undeniable impacts on the health of the Brazilian population. 111253 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Diagnosis of Heart Neoplasia, Mediastinum and Pleura in Brazil between the Years of 2013 and 2020 PAOLA BITAR DE MESQUITA ABINADER1, Ana Flavia Oliveira de Souza2, Ana Josefina Goncalves Salomao3, Camila Rodrigues Maciel4, Cecilia Gomes da Silva5, Daniel Oliveira da Costa6, Davi Gabriel Barbosa7, Gabriel de Siqueira Mendes Lauria8, Juliana Ayumi Azevedo Kurosawa9, Lucas Guimaraes Junqueira10, Rafaela Oliveira Cardoso11, Luis Eduardo Werneck de Carvalho12 (1) Centro Universitario do Estado do Para (CESUPA); (2) Centro Universitario do Estado do Para (CESUPA); (3) Centro Universitario do Estado do Para (CESUPA); (4) Centro Universitario do Estado do Para (CESUPA); (5) Universidade Federal do Para (UFPA); (6) Universidade Estadual do Para (UEPA); (7) Universidade Estadual do Para (UEPA); (8) Centro Universitario Metropolitano da Amazonia (UNIFAMAZ); (9) Centro Universitario do Estado do Para (CESUPA); (10) Universidade Estadual do Para (UEPA); (11) Centro Universitario do Estado do Para (CESUPA); (12) Clinica Oncologica do Brasil Introduction: The cardiac tumors can begging in the cardiac tissues of the internal coating, muscular layer and pericardium. Such neoplasms can show secondary symptoms and pathologies, such as: obstructions to the blood flow, dyspnea, chest pains or syncope, embolizations and arrhythmias. These clinical pictures usually show up late, and are to characterize these tumors, therefore hampering the clinical diagnosis. However, the image examinations crucial in this diagnosis are: transesophageal echocardiography, thorax tomography, magnetic resonance of the heart and even the fetal echocardiography, which allows for a diagnosis in the intrauterine phase. Therefore, the diagnosis methods in conjunction with the clinical interfere directly on the early choice of treatment and prognosis of the patients, showing the importance of the epidemiology on this pathology. Objectives: Characterize the epidemiology of the diagnosis of heart neoplasia, mediastinum and pleura in Brazil between the years of 2013 and 2020. Method: It's and epidemiological study about malignant neoplasias of the heart, mediastinum and pleura in Brazil between the years of 2013 and 2020. The data was collected on the database of the Departamento de Informatica do Sistema Unico de Saude (DATASUS). The variables analyzed here were the year and number of notifications, gender and age group. Results: In total, 3954 cases of malignant neoplasias of the heart, mediastinum and pleura were registered between the years of 2013 and 2020, with a greater incidence on males (50,9%) and a lesser in females (49,01%). Regarding the age groups, in males there was a greater prevalence of cases between 60-64 years (48,3%), while in females, the cases concentrated on the age group of 55-59 years (56%). Besides that, it was observed that 2019 was the year with the biggest number of cases, counting 1420 cases (35,9%), distributed between males and females. Conclusion: Based on the results obtained, malignant neoplasias of the heart, mediastinum and pleura affect, most of all, elderly men, with the biggest number of cases being observed in 2019. Taking on account the noted epidemiology and the difficult of identifying the risk factors and symptomatology of this type of cancer, this work puts emphasis on the need of more studies on the topic aiming to diagnose and treat the afflicted individuals early. Besides that, is primordial that the population achieves a greater access to the means of diagnosis. 111564 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Delayed Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction Patients in the Public Health System in a City of the South of Brazil LUCAS MULLER PRADO1, Jessica Tamires Reichert1, Gustavo Sarot Pereira1, Jorge Tadashi Daikubara1, Michelle Bozko Collini1, Rafael Moretti1, Matheus Bissa Duarte Ferreira1, Eduardo Leal Adam2, Miguel Morita Fernandes da Silva2 (1) Universidade Federal do Parana; (2) Complexo Hospital de Clinicas, Universidade Federal do Parana. Background: In patients with acute ST elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) is the first-choice reperfusion therapy, but fibrinolysis is recommended in non-PCI centers, when the expected time-to-PCI is expected to be more than 120 minutes (min). Objectives: To assess the time from chest pain (CP) to PCI (CP-to-PCI time) and the reasons for delay in patients with STEMI undergoing PCI in a tertiary hospital from the public health system in Brazil. Methods: We prospectively included patients admitted for STEMI in a Tertiary Hospital in Curitiba, Brazil, from Oct/2019 to Dec/2021. CP onset was the beginning of the last symptom that motivated the patient seeking care. For patients first admitted in non-PCI centers, we collected the moment the patient arrived in the emergency care unit (ECU) before being referred to the tertiary hospital. Results: We included 71 patients (61 +- 13 years old, 31% women), with 46 (65%) referred from non-PCI centers. Overall, the CP-to-PCI time was 378 [272.0, 628.0] min, and there was no significant difference between patients referred from non-PCI centers and those directly admitted in the tertiary hospital (p = 0.54). CP-to-ECU time was shorter in patients in non-PCI centers than those directly admitted in the tertiary hospital (104.5 [47.0, 206.5] vs 170.0 [123.0, 339.0] min, p = 0.012), but this was offset by a delay between the non-PCI center ECU and the tertiary hospital (172 [116.0, 335.0] min), with 74% of patients taking longer than 120 min . Conclusion: We found important delays in primary PCI in patients with STEMI treated in the public health system in a city of Brazil, with time of referral from non-PCI centers to the tertiary hospital being largely responsible for these delays. 111957 Modality: E-Poster Scientific Initiation - Non-case Report Category: DYSLIPIDEMIA Screening for Dyslipidemia and its Risk Factors in Children and Adolescents Residents in Riverside Communities in the Western Amazon GABRIEL IRISMAR RODRIGUES SCHWAMBACK1, RAIMUNDO BENICIO DE VASCONCELOS NETO1, REBECCA SHAIANE SOARES NUNES RIVOREDO1, BRENDA DOS SANTOS RODRIGUES1, SOFIA DOS SANTOS SOUZA1, JADE GOMES DA COSTA MEDEIROS1, LIANA MIRANDA PEREIRA1, ANA JULIA OMODEI RODRIGUES MARTIM1, ANTONIETA RELVAS PEREIRA2, JULIANA DE SOUZA ALMEIDA ARANHA CAMARGO1, SERGIO DE ALMEIDA BASANO1, LUIS MARCELO ARANHA CAMARGO1 (1) Centro Universitario Sao Lucas - UNISL; (2) Centro Universitario Aparicio Carvalho - FIMCA Introduction: Measuring the prevalence of dyslipidemia and its risk factors is necessary to enable the design of interventions and management of population health. However, it is observed that these data are scarce in the Western Amazon, especially regarding the monitoring of children living in riverside communities. Objectives: To estimate the prevalence of dyslipidemia and associated risk factors in children and adolescents residing in riverside communities in the Western Amazon, Brazil. Methods: The present cross-sectional study was carried out with individuals aged between 6 and 16 years, living in the riverside region of the Madeira River, in Humaita (S 6o 58'62" and W 62o 50" 08W), Amazonas State, Brazil. The project has been approved by the research committee of the Brazilian Research Center for Tropical Medicine in Rondonia (CEPEM). For the research, a clinical-epidemiological questionnaire was applied, as well as 10 mL of blood samples were collected and analyzed, as established in the parameters of the V Brazilian Directive on Dyslipidemia and Prevention of Atherosclerosis. The analysis was performed by applying the prevalence ratio (PR), Mantel-Haenszel chi-square test, with statistical significance p < 5%. Results: It was possible to analyze the data of 131 (82%), among 160 children and adolescents, being 63 females and 68 males. Eleven blood samples were found with serum values consistent with dyslipidemia, representing an absolute prevalence of 8.4%. The mean age of the sample was 11 years, ranging from 6 to 16 years. The average family income reported was calculated at R$ 809.16. For risk factors, the PR between dyslipidemia and female sex was equal to 2.0 (p = 14%); for a family history of dyslipidemia, the PR was 1.66 (p = 21%); for obesity the PR was 1.9 (p = 28%); and for sedentary lifestyle and systemic arterial hypertension, PR values were lower than 1, with p > 5%. Conclusion: Dyslipidemia is poorly studied disease in remote communities, especially when the target audience is children and adolescents. The data point to a prevalence of dyslipidemia of almost 10%, considered high for children and requiring intervention by the health system to mitigate the occurrence of chronic non-communicable diseases in adulthood. In this study, no proven risk factors associated with dyslipidemia were found. 111633 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Impact of COVID-19 on the Treatment of Conduction Disorders in Brazilian Public Health System IDRYS HENRIQUE LEITE GUEDES1, Kleber Oliveira de Souza1 (1) Universidade Federal de Campina Grande Introduction: In the global pandemic scenario and crisis in the Brazilian health system, the restriction of medical care for diseases other than COVID-19 infection triggered vast effects in the treatment of various pathologies. Therefore, it is important to analyze the consequences of this situation specifically on the treatment and management of patients with conduction disorders and cardiac arrhythmias, given the complexity of these conditions. Objectives: Collect and analyze hospitalization, hospital stay, and death data for conduction disorders and cardiac arrhythmias in Brazil. Methodology: Cross-sectional quantitative study on the treatment of conduction disorders and cardiac arrhythmias in Brazil from January 2018 to December 2021, based on data obtained from the SUS Hospital Information System (SIH/SUS), through the Ministry of Health database (DATASUS), and analyzed using IBM SPSS statistical software. The following variables were included: year of care, hospitalizations, the average length of stay, and the number of deaths. Results: There were 64790 and 69673 hospitalizations due to conduction disorders and cardiac arrhythmias in Brazil in 2018 and 2019, respectively, while in 2020 and 2021 there were 60362 and 59834 hospitalizations, resulting in a 14% difference between the highest and lowest values and a P-value <0,001. The average hospital stay in the pre-pandemic biennium increased from 4.75 days to 4.3 days (P-value of 0.978), while the number of deaths increased from 7153 and 8500 to 8576 and 8674, with a respective P-value < 0,001. Conclusion: According to the analysis, there was an indication of a significant reduction in the number of hospitalizations, a likely result of the low demand for medical care in the pandemic period. It is still possible to observe a lower number of days of hospital stay in the post-pandemic period, probably contributing to the growth in the number of deaths observed, which is also favored by the greater severity in the evolution of patients who delayed medical follow-up for too long. 111513 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION The Impact of Renal Sympathetic Denervation to the Treatment of Resistant Hypertension MARIA RAFAELA ALVES NASCIMENTO1, Yure Batista Sousa1, Leticia Rego Borborema1, Victoria Liery Ribeiro Alves1, Lara Carneiro Magalhaes1, Livia Caroline Bemquerer Veloso1, Karolina Campos Sampaio Lopes1, Fernando Guimaraes Fonseca1, Lanuza Borges Oliveira1, Maria das Merces Borem Correa Machado1 (1) Centro Universitario FIPMOC - Afya Introduction: Systemic arterial hypertension (SAH) is a considerable risk factor for cardiovascular diseases. Resistant hypertension (RH) diagnosis can be reached through the management of elevated levels of blood pressure (BP), despite the use of three or more antihypertensive medications of different classes, including diuretic ones. The sympathetic nervous system (SNS) plays an essential role in elevating BP through peripheral and central mechanisms which have an impact on the kidneys, the heart and blood vessels. The use of invasive procedures for RH treatment has recently been proven to be effective. Renal denervation modifies the sympathetic interactions between the kidneys and the central nervous system through a percutaneous procedure by connecting a catheter to a radiofrequency device. Objective: To observe the impact of renal sympathetic denervation to the treatment of resistant hypertension. Method: Systematic review has been used, with articles found in the SciELO database as well as in the Biblioteca virtual em saude, LILACS, and Medline databases. The keywords "renal denervation", "resistant hypertension", and "sympathetic nervous system" have been used in research, with the use of PRISMA methodology. Nineteen papers published in the last ten years have been selected; ten of which published in Brazil and nine others published internationally. Results: Based on the positive results of the pilot study, a new study has been encouraged: the Symplicity HTN-2. In this trial, 106 RH patients were randomly selected for renal sympathetic denervation (RSD) (n = 52, initial average BP of 178/96 mmHg) or underwent previous treatment (n = 54, initial average BP of 178/97 mmHg). After six months of observation, it was possible to determine a decrease of systolic blood pressure higher than 10 in 84% of patients subjected to RSD. In the control group, only 35% of patients showed positive results. Finally, 20% of patients from the intervention group showed decrease in the amount of medication used, as compared to the control group, which showed only 6% of patients. Conclusion: With the data collected from the study, it is possible to conclude that RSD is an efficient procedure in light of RH diagnosis, which showed no relevant complications or adverse effects and has proven to provide significant increase in the quality of life of patients who have been subjected to such treatment. 111479 Modality: E-Poster Scientific Initiation - Non-case Report Category: SPIRITUALITY AND CARDIOVASCULAR MEDICINE Association between Spirituality/Religiosity and Risk Factors for Cardiovascular Diseases BRUNA SOUZA MATOS DE OLIVEIRA1, Adelle Cristine Lima Cardozo1, Jose Icaro Nunes Cruz1, Camille Marques Aquino1, Jade Soares Doria1, Giulia Vieira Santos1, Juliana Maria Chianca Lira1, Gabriela de Oliveira Salazar1, Philipi Santos Soares1, Antonio Carlos Sobral Sousa2, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira2 (1) Federal University of Sergipe; (2) Rede D'Or Sao Luiz - Sao Lucas Hospital; (3) Primavera Hospital Introduction: Several studies analyze the influence of spirituality and religiosity (S/R) on the lifestyle of individuals. It is known that sedentarism, smoking and high alcohol consumption are risk factors for cardiovascular disease, the leading cause of global morbidity and mortality. Objectives: To analyze the relationship between S/R levels with the variables sedentarism, smoking and alcohol consumption. Methods: Observational, cross-sectional, analytical study. The sample included patients from cardiology outpatient clinics of three hospitals in Sergipe. Three natures of religiosity were assessed according to Duke Religiosity Index (DUREL): organizational (OR), non-organizational (NOR) and intrinsic (IR). The cut-off point for defining low or high level of OR and NOR was 4 (<4: low; >=4: high), while the cut-off point for low or high level of IR was 13 (<13: low; >=13: high). The variables alcohol consumption, smoking, and sedentary lifestyle were assessed by applying a self-questionnaire and their prevalence was compared between the OR, NOR and IR groups using Fisher's exact test, with the significance level set at 0.05. Results: 130 patients were included in the study, of which 62.3% were female. The mean age was 60.6 +- 11.2 years. In this sample, 73.8% were hypertensive, 59.2% were dyslipidemic, 40.8% had chronic coronary syndrome, and 35.4% had diabetes mellitus. Patients with low level of NOR had higher prevalence of alcohol consumption when compared to high level patients (71.4% vs. 28.9%; p < 0.05). Individuals with low level of IR showed higher prevalence of alcohol consumption compared to individuals with high level (61.9% vs. 25.0%; p < 0.05). There was no difference between patients with low or high level of OR for the prevalence of alcohol consumption, smoking, and sedentary lifestyle (p > 0.05). There was no difference between patients with low or high level of religiosity for the prevalence of smoking and sedentary lifestyle (p > 0.05). Conclusions: Patients with high levels of NOR and IR had lower prevalence of alcohol consumption compared to patients with low levels. The prevalences of the risk factors evaluated were not different between patients with high and low OR. There was no difference between patients with low or high levels of religiousness for the prevalence of smoking and sedentary lifestyle. Future studies with larger numbers of participants are needed to better understand this association. 111580 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Trend in Mortality Due to Hypertensive Diseases According to Underlying Cause and Mentioned Cause in Brazil from 2000 to 2019 RENATTA KAROLINE BEKMAN VOGAS1, Jonatas Benarroz da Silva1, Davi da Silveira Barroso Alves1, Paulo Henrique Godoy1 (1) Federal University of the State of Rio de Janeiro - UNIRIO Introduction: Hypertensive diseases (HD) have a high prevalence and are a risk factor for cerebrovascular and coronary diseases. They are one of the main causes of death in Brazil, however, its participation as the underlying cause of death (UCD) may be underestimated due to the selection rules of the International Classification of Diseases (ICD-10). Objective: To analyze the trend in mortality by underlying cause and by mentioned cause due to hypertensive disease, according to age and sex, in Brazil, from 2000 to 2019. Methods: Ecological study with a description of a historical series on deaths due to HD, reported as UCD or mentioned cause (MC) in lines A to D, recorded in Mortality Information System databases, in Brazil, from 2000 to 2019, based on ICD-10 codes for HD (I10-I15). Crude and standardized mortality rates were estimated for UCD and MC, according to sex and age groups. Results: There were 814,722 deaths whose UCD was HD and 3,714,982 deaths recorded as MC. The number of deaths was 4.5 times higher in the case of MC than when considered the UCD. Mortality rates as MC were significantly higher than when considered as UCD and there was a proportional increase according to age groups, especially in males, aged 30-59 years. Trends observed in the 0-29 age group were the ones that most differed, for the sexes, according to UCD and MC. Conclusions: It seems reasonable to use mentioned cause of death as a method to analyze mortality due to HD and minimize possible underestimations due to UCD selection rules, especially when considering younger groups. 111358 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The use of Ambulatory Internal Jugular Vein Ultrasound to Evaluate Congestion in Patients with Heart Failure - A Systematic Review MAYARA GABRIELE TOLEDO1, Mayara Gabriele Toledo1, Caio Pluvier Duarte Costa1, Eduardo Thadeu de Oliveira Correia1 (1) Universidade Federal Fluminense Introduction: One of the key therapeutic aims of the outpatient management of heart failure (HF) is to treat peripheral and pulmonary edema. However, although clinical signs can identify patients with congestion, it may still be present subclinically, which is an indicator of a worse prognosis. Therefore, this study aims to systematically evaluate the use of internal jugular vein (IJV) ultrasound to detect congested HF patients seen in outpatient clinics. Methods: We conducted a systematic review following the PRISMA guidelines. Original studies indexed by Embase, Pubmed, Cochrane and LiLACS with the keywords: "ultrasound" or "ultrasonography" and "heart failure" and "jugular vein" published until March, 2022 that matched the inclusion criteria were included. Two authors (C.P and M.T.) performed the screening and data extraction, in cases of discordance, a third author (E.T.) made the decision. Results: Six studies were included with a total of 1236 patients analyzed, excluding control patients. Due to the significant heterogeneity between studies, a meta-analysis was not conducted. For the ultrasonic assessment of volume status, 4 studies used the variation of the IJV diameter at rest and during the Valsalva maneuver, 1 used the variation of cross-sectional area (CSA) at rest and after the Valsalva maneuver before and after the use of diuretics, and 1 study compared the measurement of right atrial pressure (RAP) estimated by IJV ultrasound with the value obtained during right heart catheterization. One of the studies that analyzed the variation of IJV diameter at rest and during the Valsalva maneuver showed that jugular vein distention (JVD) is a valid option to assess fluid status of patients and provides diagnostic and prognostic information similar to natriuretic peptides. Pellicori et al, in their 2 studies showed that resting JVD was lower in controls (0.16 and 0.17 cm) than in HF patients (both 0.23 cm) and the JVD ratio was higher in controls (both 6.3) than in HF patients (4.5 and 4.4). In one of his studies, he showed that JVD was similar during Valsalva (1.03 cm vs 1.08 cm) in controls and HF. Conclusion: This systematic review shows that IJV ultrasound is useful for examining intravascular volume status and identifying congestion. Future clinical trials evaluating whether IJV ultrasound could be used to guide diuretic therapy are needed. Finally, further studies are needed to define a standard IJV ultrasound technique to examine volume statu. 111754 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Transcateter Aortic Valve Implantation (TAVI) in a High Complexity Center in the Western Brazilian Amazon: A Case Series REBECCA SHAIANE SOARES NUNES RIVOREDO 1, Rebecca Shaiane Soares Nunes Rivoredo1, Raimundo Benicio de Vasconcelos Neto1, Gabriel Irismar Rodrigues Schwamback1, Paulo Roberto de Oliveira Molina4, Isabel Bussinguer Gomes1, Ingrid da Silva Morais Freitas4, Francisco Siosney Almeida Pinto2 (1) Centro Universitario Sao Lucas/Afya UNISL; (2) Instituto ; (3) Centro Universitario Aparicio Carvalho Introduction: Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure that, since its debut in 2002, evolved to become the standard care for patients with aortic stenosis (AS) at intermediate and severe risk to surgery once conventional surgery as the femoral approach can be safely implemented. Over the years, there has been a significant improvement in the development of transcatheter heart valves (THV), in addition to the refinement of the skills involved in the implant process, which made it possible to increase the spectrum of patients who benefit from TAVI. Currently, studies are investigating the role of TAVI in patients at low surgical risk, new indications and new alternatives for perioperative management. Objectives: This is a descriptive study of TAVI cases performed in a high complexity hospital located in the Western Amazon. Methods: The data presented were obtained through research via medical records, complementary exams and databases such as PubMed and Google Academy. Results: In the period between September 2019 and November 2021, 11 TAVIs were performed by the cardiology team of a high complexity hospital in the Western Amazon. Patients undergoing TAVI are 5 women and 6 men, with an average age of 65.8 years, of which only one underwent the procedure on an emergency basis. The main symptom reported by patients before implantation was dyspnea on minor exertion and at rest, this symptomatology is justified by the diagnosis of severe aortic stenosis associated with heart failure NYHA > 3. The implants were performed using the Inovare(r) expandable balloon prostheses, introduced by catheter via the femoral artery with a unanimous duration of approximately 2 hours per procedure. A total of 7 patients evolved with a good prognosis without aortic regurgitation and after 24 hours of hospitalization in the intensive care unit, they were discharged from the hospital six days after the procedure and consequent progressive decrease in associated symptoms. From the sample space, 4 patients died, due to non-surgical causes. Conclusion: The data presented show the effectiveness of the procedure in patients of high and medium complexity. Therefore, the preparation and efficiency of the cardiology team responsible for managing cases and modifying the prognosis of patients who benefit from TAVI in this region of the country is of remarkable importance. 111405 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Recanalization of Coronary Chronic Total Occlusions in the Daily Practice: Insights from a Multicenter Registry in Latin America FRANCIELE ROSA DA SILVA1, Lucio Padilla2, Antonio Carlos Botelho3, Joao Eduardo Tinoco de Paula4, Carlos Augusto Homem de Magalhaes Campos,5, Marco Alcantara6, Ricardo Santiago7, Franklin Leonardo Hanna Quesada8, Felix Damas de Los Santos9, Marcia Moura1, Pedro Piccaro de Oliveira1, Alexandre Schaan de Quadros1 (1) Instituto de Cardiologia do Rio Grande do Sul (ICFUC); (2) Instituto Cardiovascular de Buenos Aires; (3) Hospital Sao Jose do Avai; (4) Instituto Cardiovascular de Linhares (UNICOR); (5) InCor; (6) Centro Medico 20 de Noviembre ISSSTE; (7) Hospital Pavia Santurce; (8) Clinica Comfamiliar; (9) Instituto Nacional de Cardiologia Ignacio Chavez Background: Chronic total occlusion (CTO) percutaneous coronary interventions (PCI) has been increasingly performed worldwide, but there is few information in Latin America. Objectives: To assess contemporary CTO PCI in the daily practice of Latin America. Methods: Centers volunteered to participate, and no minimal number of procedures was required. The databank was managed in a REDCap platform, and clinical, procedural and outcome data were evaluated. Predictors of unsuccessful procedures were assessed by multivariable analysis. Results: Data from 2.968 CTO PCIs performed in 63 hospitals from Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Mexico and Puerto Rico was analyzed. Most patients were male (78%) with a mean age of 64.0 +- 10.7 years. CTO PCI was performed mainly for angina control (83%) and/or to treat significant ischemia (30%). Radial access, dual injections and a microcatheter were used in most cases. The overall success rate of CTO PCI was 85%. The successful strategy was antegrade wire escalation in 80%, retrograde approach in 10% and antegrade dissection reentry in 10%. Proximal cap ambiguity, blunt stump, calcification, and previous attempt were predictors of unsuccessful procedures. In-hospital major adverse cardiovascular events occurred in 1.6% of the cases, and at the one-year follow-up 82% of the patients remained free of angina. Conclusions: CTO PCI in Latin America has achieved a high rate of angiographic and clinical success with low complication rates in centers dedicated to these procedures. 111406 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Relationship between Smoking and Occurrence of Amputation in Diabetes Associated with Systemic Arterial Hypertension: An Epidemiological Analysis in the State of Para MATHEUS RICARDO MALVEIRA CAMACHO1, Amanda Gabriela Freitas Rodrigues2, Wellen Sampaio Ferreira1, Izaura Maria Vieira Cayres Vallinoto2 (1) Universidade do Estado do Para; (2) Universidade Federal do Para Introduction: The association between diabetes and hypertension is a public health problem with great socioeconomic impact, being responsible for great morbidity and mortality - generating high rates of hospitalization and burden on the Brazilian Unified Health System. Among the most common late complications of hypertensive and diabetic patients is amputation, a condition that requires a considerable amount of resources in its treatment and is associated with a significant reduction in the quality of life of patients. Added to this, recent studies demonstrate that the association between smoking, diabetes and hypertension may be responsible for early death due to macrovascular complications. Objectives: To analyze the influence of smoking on the occurrence of amputations among the population that has both hypertension and diabetes. Methods: A quantitative research was carried out in a secondary database using the digital platform of the Department of Informatics of the Unified Health System (DATASUS). Data referring to hypertension associated with diabetes between the years 2003 and 2013 in the geographic scope of the state of Para were selected, analyzing the following variables: smoking and amputation. The data were worked with the help of tabulators for the Internet and for Windows (TABNET and TABWIN). The data found were analyzed by Pearson's chi-square statistical test using the Biostat software. Results: During the study period, 56,974 cases of hypertension concurrent with diabetes were reported in the state of Para. Among the registered cases, 1632 (2.86%) were smokers, while 55,342 (97.14%) were non-smokers. Among the total of smokers, 578 progressed to amputation, making 35.42% of the participants in this group. On the other hand, among non-smokers, amputation occurred in 12,049 patients, a figure that represents 27.83% of this group. When calculating the p-value of the data, a value <0.0001 was obtained; therefore, there is a statistically significant difference in the occurrence of amputations between smokers and non-smokers. Conclusions: There is an important relationship between the occurrence of amputations in patients with hypertension concomitant to diabetes and smoking in Para. This data is in agreement with the current literature and signals the need for public policies related to the prevention of hypertension and diabetes, as well as encouraging smoking cessation in the state. 111407 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Impact on Short-Term Outcomes of using a Coated Cardiopulmonary Bypass Circuit in Cardiac Surgery at a Referral Hospital KARLA SANTOS PINTO1, Luiz Carlos Passos1, Rodrigo Morel1, Diogo Azevedo1, Jackson Brandao1, Clara Salles1, Mariana Barauna da Silva1, Joao Pedro Martins Moreira Granja1, Beatriz Barbosa Viana1, Elias Soares Roseira1, Livia Maria Goes Lemos1, Raissa Barreto Lima1 (1) Hospital Ana Nery Introduction: The surgical technique with Extracorporeal Circulation (ECC) is used as the technique of choice in most cardiac surgeries, whether myocardial revascularization or valvular revascularization. However, CEC acts as an aggressor agent due to the diversion of blood to an artificial circuit. This tool puts the patient at a greater risk of developing coagulopathies, infection and vasoplegia, due to the inflammatory response. Therefore, new technologies are being developed to minimize these risks, such as ECC with endothelial biological material coating. Goal: To assess the impact on mortality and in-hospital outcomes of the use of a covered circuit for cardiopulmonary bypass Methods: This is a prospective cohort with all patients undergoing cardiac surgery using ECC from March 2021 to February 2022, in a referral hospital in Salvador, Bahia. For analysis, they were divided into group 1 (use of the coated circuit) and group 2 (use of the standard circuit); there was no prerequisite for the use of the coated circuit, it was defined in a semi-random way in the distribution of operating rooms. Surgical mortality, length of stay in the intensive care unit (ICU), length of mechanical ventilation (MV) and time of vasoactive drug use (VAD) were evaluated. Statistical significance was considered for p < 0.05. Results: A total of 292 patients were included, 104 (40.5%) using an ECC coated circuit. Of the patients, 128 (43.8%) were female and 152 (52.0%) of the surgeries involved valve approach and 140 (48.0%) underwent myocardial revascularization. The Euroscore II mean was 1.77% (+-1.5). There was no difference in mortality, in the duration of mechanical ventilation: 7 (4-12) versus 5 (3.8-9); p = 0.058, DVA use: 23 (0-46.5) versus 24 (2.8-48); p = 0.950 or length of ICU stay: 3 (2-4) versus 3 (2-3); p = 0.057, respectively, for groups 1 and 2. Conclusion: The use of a coated cardiopulmonary bypass circuit did not reduce mortality, duration of vasoactive drug use, length of stay in the ICU or time of use of mechanical ventilation. 111821 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Correction by Cor Triatriatum in Brazilian Regions in 10 Years SARA CRISTINE MARQUES DOS SANTOS1, Maria Luiza Silva Barbosa1, Alice Machado de Sales Silva1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras UV Introduction: Cor triatriatum, or triatriated heart, is a rare congenital anomaly, representing 0.1% to 0.4% of congenital heart diseases1. Embryologically, it occurs when the pulmonary vein leaves a remnant in the left atrium, dividing it into three chambers. Physiologically, there is a similarity to mitral stenosis and other obstructive pathologies of the right ventricle2. This study aims to analyze the current panorama of Cor Triatriatum correction procedures performed in Brazil for 10 years and to correlate the current epidemiology with the results obtained. Methods: A systematic literature review and an observational, descriptive, and cross-sectional collection of triatriatum color correction data, available at DATASUS - SUS Hospital Information System (SIH/SUS) for a period of ten years - December 2008 to December 2018. Results: In the analyzed period, 61 hospitalizations were observed for the performance of color correction triatriatum procedures. The total expense was R $ 937,420.58, with the year 2017 being responsible for the highest cost: R $ 179,379.02. The 61 procedures were considered highly complex, of which 31 were performed on an elective basis and 30 were urgent. The total mortality rate in the 10 years studied was 12.90, corresponding to 8 deaths, a mortality rate of 50 was identified in the years 2010 and 2018, representing the highest, while the years 2009 and 2017 had the lowest rate, 11,11. The average total hospital stay was 14.6 days. The Brazilian region with the highest number of hospitalizations was the Southeast with 17 hospitalizations, followed by the Northeast region with 15, South, and Midwest with 12 and, finally, the North region with 5 hospitalizations. Among the units of the federation, the states of Sao Paulo and Minas Gerais concentrated the majority of hospitalizations, accounting for 8 each. The North region had the highest mortality rate (20.0), followed by the South region (16.67). The Midwest region had the lowest rate, with a value of 7.69. Conclusions: From the present study, it can be observed that the North region, despite having the lowest number of hospitalizations, has the highest mortality rate when compared to other regions. It is worth noting that it is a rare congenital malformation and therefore, little discussed. Also, highlight the need for the correct notification of procedures, due to the absence of certain information, to improve the current epidemiological analysis. 111418 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Association of Severe Pulmonary Hypertension and Mortality in Heart Valve Surgery in a Referral Center KARLA SANTOS PINTO1, Elias Soares Roseira1, Joao Pedro Martins Moreira Granja1, Mariana Barauna da Silva1, Beatriz Barbosa Viana1, Taina Viana1, Rodrigo Morel1, Ana Karenina1, Luiz Carlos Passos1, Clara Salles1, Livia Maria Goes Lemos1, Raissa Barreto Lima1 (1) Hospital Ana Nery Introduction: Pulmonary hypertension (PH) is one of the factors associated with high morbidity and mortality, especially in valve surgeries. It is generally associated with more severe valve disease or with an evolved natural history. Objective: To describe the association between PH and mortality in heart valve surgery, with main emphasis on patients with suprasystemic pulmonary artery pressure (PASP) with values above 100 mmHg. Methods: This is a prospective cohort including all individuals over 18 years of age who underwent heart valve surgery using ECC from January 2020 to December 2021 in a referral hospital in the city of Salvador-Ba. For univariate analysis, chi-square test was used for categorical variables and t test for continuous variables. Multivariate analysis with logistic regression was performed, in which predictors with p < 0.05 in univariate analysis or those with biological plausibility were included. A value of p < 0.05 was considered statistically significant. Results: A total of 474 individuals were included, with a mean age of 48.1 +- 14.4 years, 180 (38%) were male and the main etiology of valvular heart disease was rheumatic heart disease: 244 (51.5%), mortality estimated by Euroscore II was on average 2.34 +- 2.53. Mean PASP was 49.8 +- 19.6 and mean ejection fraction was 60.3 +- 12.1. PASP as a continuous variable was associated with higher mortality: RR 1.06 (CI 1.05-1.07); p < 0.001 and severe PH (considered as PASP > 70 mmHg) was associated with higher mortality: RR 3.7 (1.6-8.5); p = 0.005. Seven patients presented PASP above 100 mmHg, none of which evolved to surgical death. Conclusion: Severe pulmonary hypertension was independently associated with higher mortality in heart valve surgery, which is an important factor to be considered in decision making regarding the surgical risk of patients who are candidates for surgery, with perspectives of specific conducts directed to the care of pulmonary circulation and function. of right chambers in the perioperative period. 111427 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Predictors of Blood Transfusion in the Postoperative Period of Cardiovascular Surgery with Cardiopulmonary Bypass KARLA SANTOS PINTO1, Aurea Maria Lago Novais1, Elias Soares Roseira1, Larissa Xavier Gomes da Silva1, Raissa Barreto Lima1, Ana Luisa de Aguiar Almeida Silva1, Taina Viana1, Rodrigo Morel1, Luiz Carlos Passos1, Clara Salles1, Diogo Azevedo1, Ana Karenina1 (1) Hospital Ana Nery Introduction: The need for blood transfusion in the postoperative period of cardiac surgery is associated with increased surgical morbidity and mortality. For this reason, it is important to identify predictors so that we can try to optimize them or try to solve them before the procedure. Objective: To identify predictors of need for blood transfusion in the postoperative period of cardiovascular surgery using cardiopulmonary bypass (CPB). Methods: This is a prospective cohort including all individuals over 18 years of age who underwent cardiac surgery using ECC from January 2020 to December 2021 in a referral hospital in the city of Salvador-BA. For univariate analysis, the chi-square test was used for categorical variables and the t test for continuous variables. Multivariate analysis with logistic regression was performed, in which predictors with p < 0.05 in univariate analysis or those with biological plausibility were included. A value of p < 0.05 was considered statistically significant. Results: A total of 1668 individuals were included, with a mean age of 54.5 +- 14.4 years, 889 (53%) were male, 412 (25%). The majority underwent isolated valve surgery 738 (44.2%), followed by coronary artery bypass graft surgery in 672 (40.3%). The mean EuroSCORE II was 1.96 +- 2.26 and the mean baseline blood count (Hb) was 12.9 +- 2.0. There was a need for blood transfusion in 506 (30.3%). Blood transfusion was associated with higher mortality: RR 2.7 (CI 1.8-4.0); p < 0.001. The predictors of blood transfusion in the multivariate analysis were male gender: RR 1.66 (1.31-2.11) and preoperative Hb: RR 1.19 (1.10-1.28). Conclusion: Blood transfusion in the postoperative period of cardiovascular surgery with the use of ECC was associated with higher mortality. Transfusion predictors were sex and preoperative hemoglobin. Therefore, it is important to identify patients with lower levels of basal hemoglobin to attempt optimization, with possible impact on surgical outcomes 111443 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Electrocardiographic Findings Recognize Left Ventricular Aneurysm in Patients with Chagas Disease LETICIA RODRIGUES GATTI PEREZ1, Carlos Alberto Pastore2, Nelson Samesima2, Leonardo Paschoal Camacho Varoni2, Mirella E. Facin2 (1) Universidade Municipal de Sao Caetano do Sul - USCS; (2) Instituto do Coracao (InCor) - Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo Background: The clinical presentations during the chronic phase of Chagas disease may be chest pain, thromboembolism, cardiac arrhythmias, sudden death and chronic heart failure. Although the electrocardiogram (ECG) has a crucial role in the diagnosis/prognosis of chronic Chagas cardiomyopathy (CCC) complications, there is no report of any ECG aspect associated with left ventricular (LV) apical aneurysms (present in 21%-46% of cases). Objective: To characterize the ECG pattern of LV apical aneurysms in the chronic chagasic cardiomyopathy. Methods: Cross-sectional study of patients with CCC, with and without LV aneurysm. From 2012-2019, 3377 patients were consecutively enrolled. Those with a time interval of <=6 months between cardiac magnetic resonance imaging and ECG were included. Exclusion criteria were pacemaker, left bundle-branch blocks (LBBB), tachyarrhythmias, premature ventricular contractions, aneurysm in inferior wall, previous cardiac surgery and manifest coronary artery disease. Seventy-six patients were studied, 34% with aneurysm. The ECG analysis evaluated the presence of T-wave with plus-minus pattern in V2 and/or V3 and/or V4, in addition to DI and aVL leads, to identify those with LV aneurysm. In patients with LBBB+LSFB, the aneurysm was identified by the finding of ST-segment elevation in V2 >= 1 mm and a positive T-wave. Results: A T-wave plus-minus pattern in V2 and/or V3 and/or V4 and/or DI and aVL identified LV apical aneurysm with sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of 58%, 100%, 100% and 82%, respectively. ST-segment elevation in V2 >= 1 mm (in the presence of LBBB+LSFB) showed respectively 45%, 98%, 83% and 89%. The concomitant utilization of both criteria resulted in 77%, 98%, 95%, 89%, 91%, and 38 for sensitivity, specificity, PPV, NPV, accuracy and likelihood ratio, respectively. Conclusions: The presence of a T-wave with plus-minus pattern in V2 and/or V3 and/or V4, and/or DI and aVL leads, in addition to ST-segment elevation in V2 >= 1 mm with positive T-wave (in the presence of LBBB+LSFB) showed high accuracy to identify LV apical aneurysm in patients with chronic Chagas cardiomyopathy. Further prospective studies should evaluate the relationship between these new ECG findings and morbi-mortality clinical outcomes. 111446 Modality: E-Poster Scientific Initiation - Non-case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Obstructive Sleep Apnea in a Smoking Cessation Group RAFAEL MATOSO DE OLIVEIRA FIGUEIREDO1, Paula Gouvea Abrantes1, Samuel Barud Massensine1, Rodrigo Maximo Silveira1, Moises de Toledo Vilela1, Gabriela Godinho Rezende1, Amanda Goncalves Vieira Martins1, Eliane Ferreira Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Cardiology Department, Medical School, Federal University of Juiz de Fora, Minas Gerais - UFJF Introduction: Obstructive sleep apnea (OSA) and smoking have been established as prevalent and relevant risk factors for cardiovascular outcomes, such as stroke, acute myocardial infarction and death. Although their reported synergic effect, OSA can be an underdiagnosed and undervalued as a co-risk factor. Objective: Assess the prevalence of OSA in a smoking cessation group and the correlations with comorbidities and other known risk factors. Methods: A transversal study was conducted from 2021 to 2022, with six consecutive smoking cessation groups. The participants received comprehensive evidence-based support, including a multidisciplinary team care with pharmacological treatment. A STOP-Bang score of at least 5 was defined as high-risk screening for OSA, due to its high sensibility (>90%) and accuracy. Other clinical data were collected and analyzed for knowledge between the OSA positive and negative screening groups. Results: A sample of 36 smokers, 66.7% female, 56.63 +- 10.8 years old and 42.9% with low schooling (<8 years). Comparing users with measured positive OSA with the negative OSA, it was possible to verify that the prevelance of arterial hypertension (p < 0.0001), cardiac arrhythmias (p < 0.012), abdominal obesity (p < 0.049), cognitive decline (p < 0.001), anxiety (p < 0.035) and a high tendency for depression (p < 0.077) were significantly higher for the OSA group. Regarding smoking history, nicotine dependence (p < 0.002), prevalence of the smoking triggers: stress, habits and coffee use (p < 0.001, p < 0.021 and p < 0.013, respectively) and use of marijuana and crack (p < 0.002) were significantly higher in the positive screening for OSA group. Conclusion: We observed that tobacco use might be a potential factor for aggravating or developing obstructive sleep apnea. Therefore, the synergic effect goes beyond both being relevant for cardiovascular outcomes and death. These findings may suggest how both can impact the global patient health, as isolated or, more importantly, combined risk factors. 111448 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION E-Cigarette use as a Cardiovascular Risk Factor: A Systematic Review MARIA GABRIELA MEDEIROS CUNHA DE ARAUJO1, Anna Luiza Fragoso Guimaraes Costa2, Beatriz Cunha Lisboa de Medeiros Nunes3, Eduarda Caroline Lopes de Freitas4, Felipe Andrade de Lima Trindade2, Felipe Jose Cavalcanti de Albuquerque Holanda2, Joao Victor Bezerra Ramos1, Livia Farias de Holanda Furtado1, Mateus Ribeiro Fernandes Teixeira5, Quezia Valerio Brito6 (1) Universidade Federal da Paraiba; (2) Faculdade de Ciencias Medicas da Paraiba; (3) Universidade Potiguar - UnP; (4) Centro Universitario Fametro; (5) Centro Universitario de Joao Pessoa - UNIPE; (6) Universidade Nilton Lins Introduction: Electronic cigarettes or e-cigarettes (EC), used as an alternative to smoking cessation, have become popular despite the uncertain cardiovascular risk. Although toxic-carcinogenic substances are present at lower levels in ECs compared to tobacco cigarette (TC) smoking, the products in e-liquid can be harmful to health and worryingly are often consumed by a nonsmoking public, especially young people. Objective: To provide current insight into the relation of e-cigarettes and their effects and or risks of developing cardiovascular disease. Methods: This is a systematic review, using the PubMed and Scopus databases. The Mesh descriptors used were: Electronic Nicotine Delivery Systems, Heart Disease Risk Factors, Cardiovascular Diseases and their synonyms. The initial search generated a total of 1301 articles, which after using filters resulted in 113 and after inclusion and exclusion criteria, 35 articles, used for the present study, for which the PRISMA methodology was followed. Results: It is notorious the divergence on the effects and cardiovascular risks of ECs. Some studies show damage in cellular repolarization, increase in heart rate and rhythm, and mean arterial pressure, while others do not. Furthermore, most users make dual use of electronic cigarettes and combustible cigarettes, making them more vulnerable to cardiovascular risk factors than smokers of tobacco alone or never smokers, with a higher prevalence of Metabolic Syndrome, for example. Switching from conventional smoking to the use of electronic devices is associated with a potential lower cardiovascular risk compared to continuing conventional tobacco, but some studies show no useful change in biomarkers of oxidative stress. On the other hand, users who started electronic devices after conventional ones, have a substantial higher cardiovascular risk than those who have ceased smoking. However, according to imaging methods, both conventional cigarette smokers and EC users have more carotid plaque disposition and similar alteration of vascular stiffness, with no difference in inflammatory degree between them, when compared to nonsmokers. Conclusion: The use of tobacco and the use of ECs cause damage to the cardiovascular system and alter inflammatory biomarkers. However, there is still a lack of evidence-based studies on this subject, since many of the studies are based only on acute and not chronic alterations, and the irreversibility of the disease is unknown. 111449 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Relation between Pulse Wave Speed and Cardiovascular Risks Variables FERNANDA ABRAHAM LEAO1, Maria Eduarda S. Barbosa1, Raquel P. Cabus1, Marco Antonio Mota Gomes1, Waleria Dantas Pereira1, Marcia Samia Fidelix1, Annelise Machado Gomes de Paiva1 (1) Centro Universitario Cesmac Background: The onset of CVD is most often associated with genetic predisposition, sex and age, in addition to a lifestyle that includes alcoholism, smoking, physical inactivity and diet; factors that can also influence the development of Type 2 Diabetes, Dyslipidemia and Arterial Hypertension. Given this situation, it is pertinent to analyze the relation between blood pressure parameters and cardiovascular risk variables. Objectives: To analyze the relation of different risk factors with PWV as an outcome. Methodology: Identification and behavioral data were formed, risk factors were verified, and the study variables were: age, sex, smoking, sedentary lifestyle, alcoholic beverages, presence of hypertension, diabetes, dyslipidemia, in addition to peripheral parameters and blood pressure (blood pressure and pulse wave velocity) which was created by the Mobil-O-Graph(r) equipment. An anthropometric assessment (weight, height) was performed and then the calculation of the body mass index (BMI) was verified. Results: When all risk factors were observed, 58.3% of the sample had hypertension, one of the most relevant pathologies for increasing PWV and corrected for age, it was noted that SBP with a p-value of <0.01, alcoholism with a p-value of 0.04 and smoking with a p-value of 0.02 were significant in relation to PWV. Conclusion: It appears that age and sex are the main causes of increased PWV, but they are not unique components, analyzed as risk factors, and it was noted that it is not an innate factor, but a set of mortifiable conditions. 112103 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Relevance of Myocardial Changes in Functional Capacity in Patients with Chronic Chagas Cardiomyopathy ENRICO DE FRANCISCO MAGNANI1, Jhessica Macieira Pereira1, Danielle Aparecida Gomes Pereira1, Rafael Dias de Brito Oliveira1, Thayrine Rosa Damasceno1, Suelen Cristina Silva de Oliveira1, Denise Mayumi Tanaka2, Eduardo Elias Vieira de Carvalho2, Julio Cesar Crescencio2, Eduardo Rubio Azevedo2, Marcus Vinicius Simoes2, Luciano Fonseca Lemos de Oliveira1 (1) Universidade Federal de Minas Gerais - UFMG; (2) Faculdade de Medicina de Ribeirao Preto - FMRP/USP Introduction: Heart failure (HF) is one of the main disorders that characterize chronic Chagas cardiomyopathy (CCC), and it is directly related to diffuse myocarditis, ventricular dilatation and reparative fibrosis. With its development, there is a consequent reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, little is known about the factors that determine such reduction in functional capacity in CCC. Objective: To evaluate the functional capacity and identify the determining factors of the reduction of the maximum oxygen consumption (VO2peak) in patients with CCC. Methods: Observational study using 101 patients with CCC, who underwent clinical examination, cardiopulmonary exercise test (CPET) and echocardiography as part of the standard clinical evaluation. Data normality was analyzed using the Kolmogorov-Smirnov test. The association between VO2peak and clinical or echocardiographic variables were analyzed by Pearson or Spearman correlation coefficients. Multivariable linear regression analysis was used in order to identify independent clinical and echocardiographic predictors associated with peak VO2max. Results: Mean age of study patients was 56.2 +- 13.4 years. The mean left ventricular ejection fraction (LVEF) was 42.6 +- 18%, and mean VO2peak was 16.8 +- 6.1 ml/kg/min-1. VO2peak was associated with age (r = 0.44; p < 0.001), male gender (p < 0.001), functional class (FC-NYHA, r = 0.53; p < 0.001), LVEF (r = 0.51; p < 0.001), LV diastolic diameter (r = -0.38; p < 0.001), left atrium diameter (r = -0.34; p < 0.05), E wave (r = -0.32; p = 0.01) and LV mass index (r = -0.28; p = 0.006). In the multivariate analysis, only age, male gender, LVEF and E wave remained independently associated with VO2peak with adjusted R2 = 0.66. In patients who were able to assess pulmonary artery systolic pressure (PASP, n = 45) and tricuspid annular plane systolic excursion (TAPSE, n = 55), the VO2peak correlated significantly with PASP (r = -0.60, p < 0.001) and with TAPSE (r = 0.28, p = 0.04). Conclusion: In patients with CCC, disease severity (FC-NYHA), male gender, LV systolic and diastolic function, as well as pulmonary hypertension influence functional capacity. 111520 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Study of Congenital Heart Diseases in Brazil VANESSA FARIA DE ALMEIDA SCHNEIDER1, Larissa Lima Nunes1, Inaie Maiala De Almeida Miranda1, Ana Gabriela da Silva Farias1, Leandro Rozin1 (1) Faculdades Pequeno Principe Introduction: Congenital Heart Diseases (CHD) are abnormalities in cardiocirculatory structure or function that occur in the intrauterine period, being diagnosed during pregnancy or after birth. They range from communications between cavities that regress spontaneously, to large malformations that require several invasive procedures, which can result in intrauterine death, in childhood or even in adulthood. Objective: To estimate the prevalence of CHDs and their most frequent subtypes in Brazil, from the years 2017 to 2021. Methods: An observational epidemiological survey was carried out using data from the Information System on Live Births (SINASC) and DataSUS, available by the Ministry of Health. We analyzed, through descriptive statistics, the incidences at birth and the prevalence in that period, bringing information according to the country's regions for every 10,000 live births. Results: In the total of 5 years researched, 14,748 cases of Congenital Malformations Of The Circulatory System (Q20-Q28) occurred in Brazil. Its highest incidence (18.59) was in 2017 in the Southeast region. Among the subtypes of the disease, the Southeast region continues in highlight due to Congenital Malformations Of The Cardiac Septum (Q21), with a prevalence of 7.79, reaching its highest incidence (8.87) in 2017. The greatest rates of this subtype correspond to Atrial Septal Defect (Q21.1), with a prevalence of 5.09 and its highest incidence of 6.04 occurred in 2020. Another highlighted subtype concerns Other Congenital Heart Malformations (Q24), which reached a prevalence of 4.74 in the South of the country and its highest incidence of 5.17 in 2020 - its highest rates account for Unspecified Heart Malformations (Q24.9), with a prevalence of 3.77 and its highest incidence of 4.02 occurred in 2018. A fact that draws attention is that, in the sum of the 5 years, more than 65% of cases of CHD occurred in the Southeast region, information that opens valuable precedents for new research. Conclusions: It is a fact that the difficulty in diagnosing Congenital Heart Diseases represents a significant Global Health Problem, mobilizing public policies for early diagnosis, which in Brazil has the "Teste do coracaozinho" (Little Heart Test), Morphological Ultrasound Exams, and Fetal Echocardiography. Despite this, it is worth mentioning that there is a disparity in access to these resources, which represents another challenge to the issue and may indicate underreporting of cases. 111550 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Case Series of Percutaneous Balloon Mitral Valvuloplasty for Severe Mitral Stenosis Correction in a High Cardiological Complexity Service in the Western Amazon CAMILA ALENCAR DE ANDRADE1, Gabriel Irismar Rodrigues Schwamback1, Bruna Katharine Cavalcante Nascimento1, Joao Pedro de Oliveira Vicente1, Leo Christyan Alves de Lima1, Fabiana Cristina Schabatoski Passos2, Alexandre Venturelli da Silva2, Luiz Henrique Gasparelo2 (1) Centro Universitario Sao Lucas - UNISL; (2) Angiocenter Introduction: First introduced more than 40 years ago by Japanese surgeon Kanji Inoue, percutaneous balloon mitral valvuloplasty (PBMV) is performed using a balloon inflated with high pressure in a stenotic heart valve. Mitral stenosis (MS) is a serious disease that can progress to elevated left atrial pressure and pulmonary hypertension, formation of emboli, among other complications. Objectives: This is a descriptive study of registration of cases of percutaneous mitral valvuloplasty with Inoue balloon, performed in a highly complex service in the state of Rondonia, in the Western Amazon. Methods: Data obtained through research via medical records and complementary exams were used. Results: In this case series, four patients were followed, three female aged 24, 42 and 54 years and one male aged 28 years. All patients were symptomatic (complaints of fatigue and/or dyspnea). On echocardiography, they showed significant MS with a mean gradient of 13 to 20 mmHg. The procedures were performed through the right femoral vein with an Inoue balloon, through transseptal puncture performed with the aid of transesophageal echocardiography. Patients had a hospital stay of less than two days. In the one-year follow-up with echocardiographic control, they had a favorable evolution of less than moderate stenosis and insufficiency. Discussion: Correction of MS is indicated for patients with severe symptomatic mitral stenosis (dyspnea with New York Heart Association II to IV) or asymptomatic patients with complicating factors, including pulmonary hypertension or new-onset atrial fibrillation. The patient should preferably have an echocardiographic score less than or equal to 8 (with subvalvular apparatus and calcification less than or equal to 2). Patients who present pre-procedure echocardiographic score greater than 8, post-procedure mitral valve area with a value of less than 1.5 or post-procedure mitral regurgitation with a value greater than or equal to 2, will have the need for of mitral valve replacement surgery at 2 years after of the procedure. Conclusion: Although it is a recent procedure for the region when compared to large centers, performing PBMV for the treatment of severe MS in the state of Rondonia promotes a safe procedure, capable of improving the patient's quality of life and increasing life expectancy, with a relatively low risk. 111936 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Incidence of Dextrocardia in Brazil in the Last Decade: An Epidemiological Analysis BRUNA VIEIRA SILVA OLIVEIRA2, Ana Paula Fernandes Pereira2, Marla Thais Fernandes Teodoro3, Davi Marques de Souza1, Joao Victor Silva Souza1, Lara Oliveira Santana Rocha1 (1) Universidade estadual do sudoeste da Bahia; (2) Universidade federal da Bahia; (3) Faculdade Santo Agostinho Introduction: Dextrocardia is a congenital malformation that consists of a shift of the heart axis to the right side of the chest, contrary to physiological and derives from a change in the embryological process. In the literature, the overall incidence is about 10:100,000, and may be underdiagnosed in most cases. Objectives: To determine the annual incidence of the malformation in each Brazilian region during the last 10 years. Methods: Data collection in the platform of the SUS Department of Informatics - Information System on Live Births (DATASUS - SINASC), separated by region - north, northeast, south, southeast, and center-west - and year - 2010 to 2019 - with statistical calculations of the Brazilian incidence rate per 100,000 inhabitants, in order to make the data more tangible. Results: The Brazilian region with the highest incidence was the southeast, with 92 cases, and the lowest was the midwest, with 8. The year 2016 had the highest number of cases, totaling 16. Table 1 shows the relative data by region in each year. The incidence rate was about 0.5:100,000 population. Conclusions: Dextrocardia is still an underdiagnosed condition in Brazil, since the incidence rate was lower than the global rate. A result that corroborates this statement is that the southeastern region had the highest incidence in all years, perhaps due to greater access to diagnostic methods or because of a lower prevalence of complications related to the condition. 111573 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Initial Experience of the Telehealth Nucleus of the University Hospital of the Federal University of Piaui: Results of the Tele-Electrocardiogram ANTONIO MAYCON DA SILVA SOUSA1, Carlos Eduardo Batista de Lima2, Victor Eulalio Campelo2, Ginivaldo Victor Ribeiro do Nascimento2, Newton Nunes de Lima Filho2, Thiago Nunes Pereira Leite2, Jonatas Melo Neto2, Mauricio Giraldi2, Lucas Teixeira Dias2, Paulo Marcio Sousa Nunes2 (1) Universidade Federal do Piaui (UFPI); (2) Hospital Universitario da Universidade Federal do Piaui (HU-UFPI) Introduction: Telemedicine experienced strong growth after the Covid-19 pandemic. Objective: Evaluate the clinical demographic profile, rate and probability of occurrence of electrocardiographic abnormalities in the population studied in relation to sex and age. Methods: The telehealth center of the University Hospital of the Federal University of Piaui (THC UH-FUPI) uses an analysis system that allows receiving exams from peripheral units. From November 2020 to March 2022, data from patients who underwent electrocardiogram (ECG) in basic health units sent to THC UH-FUPI were evaluated. The variables analyzed were: age, gender and electrocardiographic diagnosis: unspecific changes in ventricular repolarization (UCVR), old infarction, bundle branch block, ischemia, intraventricular conduction disorder (IVCD), arrhythmias and chamber overloads. For statistical analysis, Anderson-Darling, Mann-Whitney and logistic regression tests were used with a significant p-value <0.05. Results: ECG of 27955 patients were evaluated, aged between 51.9 +- 17.3 years and predominantly female (63.0%). Of the ECGs analyzed, 6075 (21.7%) had an abnormality, with a higher occurrence with advancing age (p < 0.0001). UCVRs were more prevalent (2337; 7.96%), followed by conduction disorders (1949; 6.63%), arrhythmias (1401; 4.77%), bundle branch block (594; 2.02%), chamber overload (481; 1.64%), old infarction (359; 1.22%) and ischemia (30; 0.1%). Atrial fibrillation (AF) was observed in 138 cases (0.5%); 13% in <60 years; 87% in >60 years. Male patients were more likely to have an ECG change (OR 2.25, 95%CI 1.77-2.78), however, adjusted for advancing age, this probability cancels out. As a factor regardless of age, males had a lower chance of UCVR (OR 0.85; 95%CI 0.78-0.93), and a higher chance of arrhythmias (OR 1.29; 95%CI 1.15-1, 44), old infarction (OR 1.69; 95%CI 1.37-2.09), and ischemia (OR 1.93; 95%CI 0.93-3.99). Conclusion: In the population studied, the rate of abnormal ECGs was high (21.7%), increasing with age, with females being more prevalent. The rates of occurrence of AF and ischemia were low (0.5% and 0.1%, respectively). The main alteration was UCVR with a higher chance of occurrence in females and males were more likely to have arrhythmias, old infarction and ischemia. In this initial experience, it was observed that the tele-ECG is feasible and can be implemented, with a wide reach, even in regions where there is greater difficulty in accessing health care. 111571 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality Due to Secondary Hypertension as Underlying Cause and Mentioned Cause in Brazil and Regions from 2000 to 2019 RENATTA KAROLINE BEKMAN VOGAS1, Jonatas Benarroz da Silva1, Davi da Silveira Barroso Alves1, Paulo Henrique Godoy1 (1) Federal University of the State of Rio de Janeiro - UNIRIO Introduction: Secondary hypertension (SH) is a condition in the group of hypertensive diseases, which has a lower prevalence. Knowing mortality from SH is important, however, the lower prevalence can influence its analysis in death records. Objective: To analyze mortality due to SH, when registered as the underlying cause of death (UCD) and mentioned cause (MC), according to age group and sex, in Brazil and regions, from 2000 to 2019. Methods: Ecological study on deaths due to SH, registered as UCD and MC in lines A to D, of death certificates, from the Brazilian Mortality Information System. Code I15 of the International Code of Diseases 10 (ICD-10) was used. Crude and standardized mortality rates were estimated for UCD and MC, for Brazil and regions, from 2000 to 2019, according to sex and age groups. Results: For UCD 14 deaths were recorded, the standardized rates were similar for both sexes. The highest frequency of deaths occurred in the age group of 60 years or older. In the Midwest region, no deaths were recorded, while the Northeast accounted for 57% of deaths. As for MC, 16,892 were registered due to HS. This result is 1,200 times greater than that found in the records by UCD. There was greater disparity between the sexes than in UCD analysis, with 43% of the standardized rate for males higher than females. Standardized rates were lower in women and crude rates increased with age. The North region presented the highest standardized rate and the Southeast the lowest, in both sexes. Conclusions: It is possible that the selection rules, defined by the ICD-10, for UCD underestimate deaths from HS. Thus, it may be useful to consider MC as a method for analyzing mortality from less prevalent diseases. 111701 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Mortality Due to Malignant Neoplasms of the Heart, Mediastinum and Pleura in Brazil MARCELLA OLIVEIRA MONTE SANTO1, Afonso Moraes Melo Junior3, Ana Flavia Oliveira de Souza3, Camila Rodrigues Maciel3, Cecilia Gomes da Silva1, Lucas Guimaraes Junqueira2, Maina Cristina Santos dos Santos2, Rafael Silva Lemos2, Rafaela Oliveira Cardoso3, Paola Bitar de Mesquita Abinader3, Luis Eduardo Werneck de Carvalho4, Davi Gabriel Barbosa2 (1) UNIVERSIDADE FEDERAL DO PARA (UFPA); (2) UNIVERSIDADE ESTADUAL DO PARA (UEPA); (3) CENTRO UNIVERSITARIO DO PARA (CESUPA); (4) ONCOLOGICA DO BRASIL Introduction: Within the thoracic region there are 3 main sites of development and metastasis of malignant neoplasms: the heart, the mediastinum and the pleura. Although neoplasms in the cardiac muscle tissue are rare, there are cases of primary and secondary tumours, representing 0.05% and 1-2% of neoplasms. In contrast, pleural tumours are more common, the main cancer of which is mesothelioma in its diffuse form. In general, most tumours present in these organs are metastases from other neoplasms in advanced stages. Objectives: To establish an overview of mortality from malignant neoplasms of the heart, mediastinum and pleura in Brazil, through a time-series study, between 2011 and 2020. Methodology: This is a cross-sectional study, evaluating the information on mortality from malignant neoplasms of the heart, mediastinum and pleura in the years 2011 to 2020. A search was performed in the tabnet DATASUS system. The ICD C38 (heart, pleura and mediastinum) was selected to perform the search and comparison between the regions of Brazil. It established the stratification by age range affected, the division by gender and the total number of cases per year in the selected period. Results: In the period 2011-2020 about 7585 deaths from cancer of the heart, mediastinum and pleura, and 2019 was the year with the highest number of deaths; 867 were recorded. In 2019, the southeastern region had the highest number of deaths (45.7%). Of the total absolute deaths in the regions, 5859 (77.3%) were in ages 50 years and above, with the most prominent age group being 60-69 years with 1809. Comparing the sexes, there were more male deaths, with 4,249 (56.01%) registered, compared to the female, with 3,332 deaths (43.92%). Both genders presented a higher number of deaths in 2019, with men representing 54.09% and women 45.91%. Moreover, the highest number of deaths of both sexes was registered in the Southeastern region and the most affected age group was 60-69 years. Women presented a greater constant of deaths along the years than men. Conclusion: It appears that neoplasms of the heart, mediastinum and pleura in Brazil have a higher incidence at ages between 60-69 years. There was a predominance of male deaths, besides the southeastern region accounting for most of the deaths. Thus, it is necessary to invest in prevention actions directed to this public, in order to reduce the number of deaths from these neoplasms. 111604 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Assessment of Postoperative Pain on Cardiac Surgery Patients Randomized between Preemptive Pregabalin and Placebo: Preliminary Analysis of Pregaba-Heart Study FABIO ANTONIO SERRA DE LIMA JUNIOR1, Fabio Antonio Serra de Lima Junior1, Ana Beatriz Venancio de Paula Bezerra1, Renan Furtado de Almeida Mendes1, David Cesarino de Sousa1, Raphael Patrik Borges da Costa1, Isaac Newton Guimaraes de Andrade1, Andre Telis de Vilela Araujo1 (1) Universidade Federal da Paraiba Introduction: Cardiac surgery, through sternotomy, can cause intense postoperative pain, most commonly in the immediate postoperative period, affecting 50% of patients and may lead to significant long-term consequences, as well as chronification. Despite this, between 50% and 75% of patients do not receive adequate analgesic management. Few randomized controlled trials have addressed the efficacy of pregabalin administration in the perioperative period for pain control, delirium, and postoperative recovery, obtaining variable results. Objectives: This study aimed to evaluate the preemptive use of pregabalin to decrease pain perception in patients undergoing cardiac surgery in the first three postoperative days. Methodology: Patients, undergoing cardiac surgery, were randomized into two groups: one group will preemptively use pregabalin 75 mg on the day of surgery until the second postoperative day, and the other group will use placebo for the same period. After postoperative extubation, they were evaluated at 24, 48, and 72 hours for visual analog scale (VAS) and analgesic use. The study was registered in ClinicalTrials.gov through NCT04173390. Results: Twenty-three patients were included, with 11 receiving pregabalin and 12 placebo, presenting, respectively, visual pain scale means of 1.75 +- 2.188 vs. 2.27 +- 2.412 (p = 0.634) at 1st PO day; 0.88 +- 1.246 vs. 2 +- 2.049 (p = 0.188) at 2nd PO day; and 1.75 +- 2.915 vs. 1.64 +- 1.804 (p = 0.918) at 3rd PO day. There was no statistically significant difference in the use of simple analgesics, weak or strong opioids on any of the postoperative days. Conclusion: In this partial evaluation of the study, pregabalin did not affect patients' postoperative pain scores, nor did it affect their analgesic consumption. The study will continue to randomize and collect patients until it reaches the anticipated sample size for more adequate statistical power. 111609 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Myocardial FDG Uptake Variation and its Relationship with Survival During Immunotherapy MATHEUS COELHO TORRES1, Juliana Goes Martins Fagundes2, Luis Fabio Barbosa Botelho1, Thiago Lins Fagundes de Sousa5, Alinne Fernanda Amaral Vercosa3, Rodrigo de Carvalho Flamini3, Eudanusia Guilherme de Figueiredo2, Emilio Carlos De Arruda Lacerda2, Igor Lemos Duarte2, Jean Fabricio De Lima Pereira2, Marcelo Dantas Tavares De Melo1, Silvia Moreira Ayub Ferreira4 (1) Hospital Universitario Lauro Wanderley - UFPB, Joao Pessoa, Brazil; (2) Oncoclinicas Paraiba (Centro Paraibano de Oncologia), Joao Pessoa, Brazil; (3) Nova Diagnostico por Imagem, Joao Pessoa, Brazil; (4) Instituto do Coracao, Sao Paulo, Brazil; (5) Hospital Universitario Alcides Carneiro, UFCG, Campina Grande, Brazil Background: The rise of Immune Checkpoint Inhibitors (ICI) as a cancer treatment has been followed by the increase of cardiotoxicity events reports. Retrospective studies with anthracycline revealed a relationship between increased myocardial 18F-FDG uptake (MGU) and a slight drop in Left Ventricular Ejection Fraction values, suggesting that this may be a useful tool for early detection of cardiotoxicity. Our study is intended to evaluate the prognostic impact of the variation in MGU in advanced lung cancer undergoing treatment with ICI. Methods: This is a unicentric, retrospective study, that evaluated lung cancer patients treated with ICI from 2016 to 2021 and submitted to at least two positron emission tomography (PET-CT). The primary objective was to evaluate the MGU variation during ICI treatment (DSUV) and its impact on survival outcomes. Results: 59 patients fulfilled all inclusion criteria. 51% received Immunotherapy in combination with chemotherapy and 49% received only immunotherapy. Global median DSUV was +0.05; Among patients in the disease control group, the median DSUV was +0.48, while the median DSUV of the disease progression group was -0.66. Considering patients with positive myocardial DSUV versus negative DSUV, there was a median increase of progression-free survival (PFS) of 161 days in favour of the positive myocardial DSUV group (p = 0.066) and increase of 281 days on Overal Survival (p = 0.256). There was an increase of 759 days in the OS of diabetic patients (p = 0.023), and better results in metformin users (p = 0.015), in addition to an increase of 285 days in favor of beta-blocker (BB) users (p = 0,886). The trend data found indicate that BB and/or metformin could perhaps have a supporting role in the treatment of ICI. These findings correlate with recent evidence showing an increase in MGU after BB use and that BB may function as immunomodulatory agents improving immunotherapy results. Conclusions: The increase in MGU was associated with better outcomes, suggesting that perhaps it could be studied as a predictor of treatment response, in addition to the trend of benefit also shown with the use of metformin and BB, which strengthens their possible synergistic effect in treatment. However, more robust studies are needed to better understand the MGU role on ICI treatment. 111642 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Detection and Monitoring of Arterial Hypertension Through Residential Monitoring of Blood Pressure (MRPA) in Adolescents: A Literature Review PAOLA DE OLIVEIRA DAS CHAGAS1, Camila Alvarez Alonso1, Luz Alcira Avila Rincon Alves1, Fabiane Rosa Rezende Honda Marui1 (1) Universidade Municipal de Sao Caetano do Sul - USCS Introduction: Hypertension in adolescents has become more and more frequent due to the increase in the childhood obesity rate. In addition to obesity and overweight, stress and excessive salt intake are also factors related to increased blood pressure in this age group. The increase in cases of hypertension in adolescence has been a recent concern, since until the mid-1970s, the measurement of Blood pressure in asymptomatic children was not frequently performed, after updates to the guidelines, it is recommended that in the absence of comorbidities, the Blood pressure is measured annually. ABPM, which is the gold standard for monitoring, has been the most recommended for confirming the diagnosis of AH, but despite the recommendation, ABPM has high costs and risks of failure. Home blood pressure monitoring has shown great efficacy and sensitivity when compared to ABPM, although there are not enough studies. Method: The bibliographic survey was carried out from articles collected on the LILACS and MEDLINE platforms. Articles published between 2012 and 2021, in Portuguese, English and Spanish were eligible. The articles were initially selected by reading the titles and abstracts for categorization according to the study objectives. Subsequently, the selected ones were read in full. Results: Considering the analysis of the studies, it was identified that the ABPM obtained values similar to the ABPM when performed in adolescents and presented a better cost-benefit ratio, in addition to being more effective in identifying White apron effect and masked hypertension. Studies have shown that this accuracy prevents teenagers from being misdiagnosed and that they consequently involve unnecessary treatment with antihypertensive drugs. Final considerations: Although evidence on HBPM is still limited, the literature review points out that the values obtained through home monitoring proved to be accurate when compared to other methods and also provided information on the daily variability of the assessed public, showing be a precise alternative in confirming the diagnosis of hypertension and young people. 111648 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Hospitalizations and Deaths Due to Systemic Arterial Hypertension in a Brazilian Amazon's State GABRIEL NERY LIMA1, Arthur Afonso Ferreira Rebelo1, Thassio Marcyal Bento Ferreira1, Gisely Seguchi Spinasse1, Matheus Ricardo Malveira Camacho1, Amanda Gabriela Freitas Rodrigues2, Israel Figueira Lemos1 (1) Faculdade de Medicina da Universidade do Estado do Para; (2) Faculdade de Medicina e Cirurgia do Para Introduction: Systemic Arterial Hypertension (SAH) is a clinical condition that consists in high and sustained levels of blood pressure, generating effects in the heart, brain, kidney and blood vessels. The SAH is related with several metabolic disorders, which leads to elevated risk of cardiovascular fatal and non-fatal events. Nowadays, in Brazil, the SAH affects approximately 30% of the population and corresponds to 40% of deaths from stroke and 25% of deaths from Chronic Arterial Disease. Therefore, there is great relevance in studying the epidemiology of this disease in the country, seeking to understand which social groups are most affected by it and, thus, need greater attention from Public Health. Objective: To describe the epidemiological profile of hospitalizations and deaths due to Systemic Arterial Hypertension in the state of Para. Methods: A cross-sectional, descriptive and quantitative study was carried out using the database of the Department of Informatics of the Unified Health System (DATASUS). Data referring to patients hospitalized or who died from SAH in the period from 2008 to 2020 in the state of Para were selected, considering the following variables: age, sex and race. Data were processed using Excel and Biostat software. Results: During the study period, 55,503 hospitalizations and 508 deaths from SAH were reported in the state of Para. Hospitalizations were more frequent among women (58.5%), black and brown people (57.6%), and in the 50-69 age group (42.6%). On the other hand, deaths occurred mainly among men (51.9%), black and brown people (43%), and aged over 70 years (54.6%). It is worth mentioning that the analysis of the "race" criterion was hampered by a large number of cases without information in the system (23,097 records). Conclusion: There is greater morbidity and mortality among the non-white population, which is in agreement with the current literature, which states that there is a greater prevalence and severity of SAH among black and brown people, mainly due to genetic factors. However, it is known that in Brazil there is a historical marginalization of this population; this factor may be related to the difficulty in accessing the right to health, aggravating the risk factors for the development of SAH in this social group. In this sense, greater efforts must be made in order to reduce social inequality and promote universal access to heahealth thus minimizing unfavorable outcomes due to lack of assistance. 111649 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality Due to Acute Myocardial Infarction Among Indigenous and Non-Indigenous: The Brazilian Scenario Over the Past Decade MARCOS OLIVEIRA1, Solange Lima Gomes1, Franciane de Paula Fernandes1 (1) Universidade do Estado do Para (UEPA) Introduction: Acute Myocardial Infarction (AMI) is an important cause of mortality in society. In indigenous peoples, this illness gains prominence due to barriers that hinder access to health. Despite advances, AMI remains among the main causes of death in these peoples. In view of this, it is necessary to investigate how this situation affects the occurrence of this disorder in traditional populations. Objective: To analyze the mortality due to AMI in indigenous and non-indigenous peoples from Brazil over the past decade. Methods: This is a descriptive study, with a quantitative, cross-sectional, and retrospective approach. Data from public domains of the Mortality Information System of the Informatic Department of the Unified Health System (SIM/Datasus) were analyzed. Results: 974,862 deaths were reported in non-indigenous peoples and 1,775 in indigenous peoples. Among non-indigenous peoples, the highest number occurred in 2019. In the same group, 59% were male and 40.98% female. Furthermore, the age group of 80 years or older was predominant (26.04%) and the majority of deaths occurred in hospitals (51.24%). Among non-indigenous peoples, the highest number of deaths occurred in 2020. There was a predominance of males with 59.15%, while 40.78% were female. The most affected age group was 80 years or older (29.35%). It was also noted, a higher frequency of notifications at home (47.49%). Conclusion: This context may be a reflection of greater difficulty in accessing health facilities for the traditional population. It is evident the need for health access strategies that consider the cultural particularities of each group, in addition to awareness campaigns with a preventive approach, and research that explores prevention strategies and control of risk factors in health units. 111680 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The Impact of Comorbidities on the Prognosis of Patients with Acute Heart Failure JOSE RENAN DE MATOS PAIN1, Jose Renan de Matos Pain1, Jorge Tadashi Daikubara Neto1, Matheus Bissa Duarte Ferreira1, Rafael Moretti1, Jessica Tamires Reichert1, Lucas Muller Prado1, Gustavo Sarot Pereira da Cunha1, Leornardo Henrique dos S. Melo1, Michelle Bozko Collini1, Raphael Henrique Dea Cirino1, Miguel Morita Fernandes da Silva1 (1) Universidade Federal do Parana (UFPR) Background: Comorbidities are associated with worse quality of life and prognosis in chronic heart failure. However, there is lack of data on the impact of comorbidities in acute heart failure (AHF). Objective: To assess the association between comorbidities and the and prognosis of patients with AHF. Methods: Patients diagnosed with AHF, admitted to a tertiary hospital in southern Brazil, between 2019 and 2021 participated in the study. We selected the following comorbidities: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol consumption, anemia, stroke, atrial fibrillation, coronary artery disease (CAD), peripheral vascular disease (PVD), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). The outcome was a composed of all-cause death or re-hospitalization within 6 months. We performed a stepwise forward selection with Cox regression analysis to identify the comorbidities independente associated with the outcome. Results: We analyzed 175 patients with AHF were included, of which 66 died or were re-hospitalized during the study period. The mean age of the patients was 67 years, 88 (50%) patients were female, the mean ejection fraction was 43.8, and the ejection fraction extremes were 61.6-26.1. The five most prevalent comorbidities were: hypertension (79%), diabetes (38%), atrial fibrillation (36%), dyslipidemia (31%), CAD (29%) and COPD (18%). In the stepwise multivariate regression, the only comorbidity that was independently associated with the composite outcome was COPD (Hazard ratio 1.83, 95% confidence interval, 1.04-3.23, p = 0.035). Ejection fraction (EF) was not significantly associated with the outcome (p = 0.48). Conclusion: In patients with AHF, COPD was the only comorbidity independently associated with the risk of events in a six month follow up. 111691 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Is There a Relationship between the COVID-19 Pandemic and the Epidemiological Behavior of Acute Coronary Syndromes in Salvador-Bahia? JULIA SCHOUCAIR NEVES1, Marilia Menezes Gusmao1, Lais Araujo Carneiro de Campos1 (1) Escola Bahiana de Medicina e Saude Publica - EBMSP Introduction: The COVID-19 pandemic brought impacts that may have had a great influence on the incidence and lethality of Acute Coronary Syndromes (ACS). Since the actions to contain the pandemic have regional differences, it is necessary to know if the increase in the number of cases of COVID-19 was linked to an increase in the number of cases and mortality from ACS in Salvador. Objective: To investigate whether there was an association between cases of ACS and cases of SARS-CoV-2 infection, during the first wave of the COVID-19 pandemic, in Salvador. Methodology: Observational study of comparative incidence and temporal trend carried out using secondary data from a local public ambulance service (SAMU) registries and the COVID-19 database provided by Health Secretary of Bahia State. The monthly incidence, lethality and assessment of the association between its incidences and Pearson's correlation coefficient were performed in Excel software. Results: From April to December 2020, there were 490 new cases of ACS, attended by SAMU, in Salvador. Compared with the number of cases in the same period of pre-pandemic years (2017, 2018 and 2019), respectively 341; 484 and 496 cases, it was observed that the incidence remained constant. There was no significant correlation between the monthly incidence of COVID-19 and ACS (r = -0.1) or lethality among these two variables (r = -0.13), from April 2020 to April 2021. Conclusion: There was no increase in ACS cases registered by SAMU between April 2020 and April 2021, during the COVID-19 pandemic, in Salvador, when compared to the same period of the last 3 years and there was no significant correlation between the incidence of ACS cases and COVID-19 cases. 111705 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Screening for Systemic Arterial Hypertension and Its Risk Factors in Students Resident in a Riverside Community in the Western Amazon RAIMUNDO BENICIO DE VASCONCELOS NETO1, Raimundo Benicio De Vasconcelos Neto1, Rebecca Shaiane Soares Nunes Rivoredo1, Gabriel Irismar Rodrigues Schwamback1, Brenda dos Santos Rodrigues1, Sofia dos Santos Souza1, Maria Eduarda Brotto de Souza1, Barbara Barbosa Pires1, Antonieta Relvas Pereira2, Sergio de Almeida Basano3, Juliana de Souza Almeida Aranha Camargo4, LUIS MARCELO ARANHA CAMARGO4 (1) Centro Universitario Sao ; (2) Centro Universitario Aparicio ; (3) CEMETRON; (4) ICB-5 USP Introduction: Systemic arterial hypertension (SAH) is a chronic non-communicable disease (CNCD) with high worldwide prevalence. It is a disease that has its onset, often in childhood and adolescence, and can lead to serious future consequences. However, it appears that there is a data scarcity about the occurrence of SAH in Western Amazon communities, especially riverside communities. Objectives: To estimate the prevalence of SAH and associated risk factors in public school students residing in riverside communities in the Western Amazon, Brazil. Methods: This work is a cross-sectional study, carried out with individuals aged between 4 and 21 years old, without gender distinction, living in a riverside region in Humaita (S 6o 58'62'' re W 62o 50'' 08W), Amazonas State, Brazil. The project was approved by the research committee of the Brazillian Center for Research in Tropical Medicine (CEPEM). For the blood pressure measurement, the patients were prepared according to the protocol of the Brazilian Ministry of Health, 3 measurements were performed, excluding the first and applying the average of the last two in each arm. The analysis was performed using the prevalence ratio (PR), Mantel-Haenszel chi-square test, with statistical significance p < 5%. Results: 160 public school students were randomly selected for the study, of which 152 (95%) had their data analyzed, 82 male and 70 female. Twenty-five individuals were found with blood pressure levels consistent with SAH, representing an absolute prevalence of 16.5%. The mean age of hypertensive students was 12 years, ranging from 5 to 21 years. The average income reported was calculated at R$ 862.00. Regarding risk factors, the PR between SAH and males was 1.5 (p = 13%); for family history of SAH, the PR was 1.2 (p = 35%); for SAH and sedentary lifestyle, the PR was 1.3 (p = 30%); for the association between SAH and obesity in this population and SAH and dyslipidemia, the PR was less than 1, but with p > 5%. Conclusions: A few decades ago, CNCD, such as SAH had significance only among the adult population, now it also affect children and adolescents in a similar way. The data from this analysis point to a prevalence of more than 16% of SAH among students aged 5 to 21 years, which is considered high for this age group, requiring an intervention by the health system in order to attenuate the occurrence of NCDs in adulthood. There was no association between risk factors and SAH in this study. 111733 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Obesity Screening and Risk Factors in Riverside Schools in the Western Amazon REBECCA SHAIANE SOARES NUNES RIVOREDO1, Rebecca Shaiane Soares Nunes Rivoredo1, Raimundo Benicio de Vasconcelos Neto1, Gabriel Irismar Rodrigues Schwamback1, Jade Gomes da Costa Medeiros1, Liana Miranda Pereira1, Barbara Barbosa Pires1, Ana Julia Omodei Rodrigues Martim1, Antonieta Relvas Pereira2, Sergio de Almeida Basano3, Juliana de Souza Almeida Aranha Camargo4, LUIS MARCELO ARANHA CAMARGO4 (1) Centro Universitario Sao Lucas/Afya UNISL; (2) Centro Universitario Aparicio Carvalho FIMCA; (3) CEMETRON; (4) ICB-5 Schools in the Western Amazon Introduction: The current Brazilian epidemiological profile is undergoing a process of transition in the most gentrified regions of the country, where infectious diseases predominated, has been showing an increase in non-communicable chronic diseases. Obesity is a chronic disease considered a serious public health problem, defined by excess body fat. Its prevalence may contribute to the emergence of cardiovascular diseases. This study aimed to identify the prevalence of obesity and its risk factors in riverine schoolchildren in the Western Amazon, Brazil. Methodology: This is a cross-sectional study, carried out with individuals aged between 6 and 16 years old who attend public schools. The sample space consisted of 152 individuals belonging to 22 riverside communities along the Madeira River in Humaita, Amazonas State, Brazil. For the research, a clinical-epidemiological questionnaire was applied, in addition to obtaining anthropometric data (weight, height, waist circumference), body mass indices (BMI) were calculated, considering the guidelines of the Brazilian Ministry of Health as a standard of normality. The statistical analyzes performed were the prevalence ratio (PR), Mantel-Haenszel chi-square test, with statistical significance p < 5%. Result: The 152 individuals evaluated corresponded to 95% of the sample population aged between 6 and 16 years. The study showed 7 individuals with BMI values consistent with obesity, demonstrating an absolute prevalence of 4.6%. The age of obese individuals ranges from 6 to 16 years old, and the average family income reported was R$ 809.16, most of which came from financial Federal Government Programs. Among the risk factors, the association between obesity and family history for obesity, the PR is 0.4 (p = 40%), the PR for males is 4.84 (p = 5.7%) and finally, sedentary lifestyle and obesity have a PR that is below 1 (p = 13%). Conclusion: Little is known about the culture and epidemiological profiles of riverside communities, but with the data collected, it is observed that even in remote areas, cases of obesity are already identified. It is important to develop public policies aimed at these populations, with the objective of improving knowledge about nutrition and health, physical activity and diet, ensuring good nutrition throughout life, promoting health in addition to reducing public spending on health problems. triggered by excess weight. 111718 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Study of the Overview of Hospitalizations for Acute Myocardial Infarction between the Regions of Brazil from 2011 to 2021 NESLAYNE LOUISE CAMPIOL1, Andreisa Prieb1, Thiago Santos Souza1, Monique Veloso Lima1, Nathalia Freire Gilo1, Mauricio Antonio Batista Cavalcante1 (1) Universidade de Gurupi - UNIRG Introduction: Non-transmissible cardiovascular diseases represent a major public health problem worldwide. In Brazil, Acute Myocardial Infarction (AMI) is the leading cause of death in the country, according to DATASUS, and constitutes a process of ischemic necrosis caused by acute obstruction of a coronary artery. Therefore, a greater awareness of the measures for prevention and control of AMI is necessary, in addition to the stratification of cardiovascular risk in the population. Objective: Analyze the epidemiological profile of hospitalizations for AMI among Brazilian regions from 2011 to 2021. Methods: A retrospective, observational, descriptive, cross-sectional study was conducted on data from hospitalizations for AMI, available at DATASUS - SUS Hospital Information System (SIH/SUS), in the period from January 2011 to December 2021, evaluating several variables such as the number of hospitalizations, mean value, mean length of stay, number of deaths and mortality rate. Results: In the period studied, 1,187,982 hospitalizations for procedures to treat AMI were observed, representing a total expenditure of R$ 4,378,770,679.45. The Southeast region recorded 593,441 hospitalizations, corresponding to half of the entire country, followed by 233,365 in the Northeast (19.6%), 232,330 in the South (19.6%), 81,086 in the Midwest (6.8%), and 47,760 in the North (4.02%). The total number of deaths in Brazil was 130,209, being higher in the Southeast with 63,517 (48.8%) and in the Northeast with 28,506 (21.9%). The mortality rate in Brazil was 10.96, with the Northern and Northeastern regions above the national average, 12.22 and 12.04, respectively; and the other regions below the national average, Southeast (10.70), South (10.36), and Center-West (10.32). The national average stay was 7.3 days, while in the North it was 8.2, followed by 7.7 in the Northeast and Southeast, 7.3 in the Midwest, and 5.6 in the South. Concerning the average value of hospitalization, the highest value was in the South, R$4,417.68, followed by the Southeast R$3,695.58, Center-West R$3,503.92, Northeast R$3,194.34, and North R$2,716.46. Conclusions: It is important to emphasize the importance of promotion and prevention in primary health care and early diagnosis to avoid sequelae and reduce the risk of death in patients. In addition, it reinforces the need for correct notification so that the information can help in the development of public health policies. 111726 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Study of Pacemaker Implants in the City of Rio de Janeiro LEO RODRIGO ABRAHAO DOS SANTOS1, INGRID PAIVA DUARTE1, ANDRE MELO DE FARIA1, MATHEUS SOUZA DE MOURA RIBEIRO1, NATALIA MELO DUARTE DE ALMEIDA1, LUANA TEIXEIRA DA SILVA1, LUIZA FURTADO AREAS1, THATIANA DA SILVA PIRES1, DANIEL ALBUQUERQUE MARTINS ZANIBONE1, THIAGO CAVALHEIRO TAVARES1, LUIS ORLANDO POZES PEREIRA FILHO1, OGI JANDERSON ANTUNES DE CASTRO BRITO1 (1) Unigranrio-Afya, Rio de Janeiro, Brazil Introduction/Objectives: Artificial Cardiac Pacemakers are devices capable of replacing electrical impulses through multiprogrammable stimulation to achieve physiological cardiac electrical activity. They are classified by clinical need as Temporary or definitive, by transcutaneous route, transvenous or thoracotomy, by the types of endocavitary and epicardial cable, single chamber stimulated chambers, double, triple or the four chambers. The study aims to know epidemiologically the population that underwent pacemaker implantation in thecity of Rio de Janeiro. Materials/methods: The collection of data was made in the hospital information system of the municipality of Rio de Janeiro from January 2010 to December 2020, researching race, age, type of pacemaker performed, hospitalizations, mortality and expenses. The present study is observational, descriptive and cross-sectional. Results: The study found records of 5031 patients who underwent the procedure, 4063 (81%) were Transvenous Double Chamber Pacemakers, 564 (11%) of Transvenous Single Chamber, 219 (4%) of Transvenous Multi-site, 73 (2%), of Epimyocardial Double Chamber, 56 (1%) Temporary Transvenous, 30 (1%) of Single Epimyocardial Chamber, 21 (<1%) of Multi-site Epimyocardial by Thoracotomy for Thoracotomy for electrode implant and 5 (<1%) multi-site Endocavitary with reversal to epimyocardial. The majority were attended at the Instituto de Cardiologia Aloysio de Castro (IECAC) which totaled 1524 (30.3%) procedures. 3238 (64%) performed the implant electively. 73% were over 65 years old. 44% were White. 2547 (51%) were Men. The average length of hospital stay was 5.44 days and an average expenditure of US$ 2,552. In addition, 2499 (49.7%) had a daily ICU with an average expenditure of US$ 3,125. The most expensive procedure was the Transvenous Multi-site pacemaker with an average cost of US$ 5875.6. There were 84 deaths in general, 61% in Transvenous Double Chamber Pacemakers, the highest mortality rate was found in patients who underwent temporary transvenous pacemaker implantation with 25% of deaths. Discussion/Conclusion: Patients undergoing pacemaker implantation have a profile mainly of elderly males, whites who perform Transvenous Double Chamber Pacemakers mostly in high complexity cardiac hospitals. These data, in addition to characterizing users, show how costly, complex and common the use of these devices is, and the need for investment in cardiology services in the city. 111746 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Evaluation of Chronic Rheumatic Heart Disease Admissions in the Northern Region of Brazil between 2017 and 2021 IGOR LUCAS FARIAS LIMA1, Luciano Moura de Assuncao3, Giulia Vitoria Nascimento da Silva1, Ariane Lobato Moraes2, Marcos Aurelio Vieira da Costa Filho2, Wanda Maria de Franca Pires2, Larissa Dacier Lobato Comesanha2, Julia de Moura Carvalho Faria1 (1) UNIVERSIDADE DO ESTADO DO PARA - UEPA; (2) UNIVERSIDADE FEDERAL DO PARA - UFPA; (3) FUNDACAO SANTA CASA DE MISERICORDIA DO PARA Introduction: Chronic rheumatic heart disease (RHD), a sequel of rheumatic fever (RF), is caused by lesions that mainly affect mitral and aortic valves, and late diagnosis results in major complications such as heart failure, pulmonary hypertension and atrial fibrillation1. The primary prevention of RHD consists of the diagnosis and treatment of streptococcal pharyngitis and secondary prevention in long-term antimicrobial prophylaxis in individuals with a previous diagnosis of RF2. Objective: To assess the prevalence and analyze the epidemiological profile of RHD hospitalizations in the Northern Region of Brazil from 2017 to 2021. Methods: Observational, cross-sectional, descriptive and quantitative study based on data from the SUS Hospital Information System (SIH/SUS) - DATASUS. The variables analysed were: number of hospitalizations, age, sex, average hospital stay, average cost per hospitalization and mortality rate, referring to hospitalizations due to RHD in the Northern region of Brazil between 2017 and 2021. Results: In the analyzed period, 1744 hospitalizations for RHD were reported in the Northern Region of Brazil, with the highest number of hospitalizations in the state of Para (697). In the North Region, the largest amount occurred in 2017 with 468 cases, with a gradual decrease until 2021 with 246 hospitalizations. Regarding gender, 51.15% of the hospitalized patients were female and 48.85% were male. The most affected age groups were 50 to 59 years old, with 308 (17.6%) notifications, and 40 to 49 years old, with 297 (17%) cases. The average length of stay in 2017 to 2021 was 13.1 days, being highest in Rondonia (15.1 days) and lowest in Roraima (7.3 days). In the North region, the lowest average time (11.1 days) occurred in 2020 and the highest (14.7 days) in 2017. The mortality rate was 7.91%, being the lowest in 2018 (6.14%) with gradual growth until 2021 (10.16%). The state with the highest mortality rate was Roraima (28.57%) and the lowest was Amazonas (6.53%). A total of R$16,878,115.65 was spent in the considered period, with an average cost of R$9,677.82 per hospitalization. Conclusion: The study reports that the highest number of hospitalizations occurred in 2017, mostly in the state of Para. Mortality rate due to RHD is rising and the highest rate comes from Roraima. In addition, the most affected age group was 50 to 59 years, and there was no significant difference in prevalence between genders. 111751 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Long-Term Impact of COVID-19 on the Practice of Physical Exercise in Patients with Heart Disease: A Cohort Study in the Brazilian Amazon LUANA LIVELLI BECKER1, Kletey Mendes Silva1, Odilson Marcos Silvestre1, Miguel Fernandes da Silva Morita2, Dhayn Cassi Freitas1, Roberta Gabriela da Silva1, Lais Vitoria de Andrade Miranda1, Sabrina da Silva Medeiros1, Emanuel Silva de Abreu1, Jessica Borsoi Maia do Carmo1, Leonardo Buranello1, Wilson Nadruz3 (1) Federal University of Acre; (2) Federal University of Parana; (3) University of Campinas Introduction: The impact of COVID-19 infection in patients with heart disease remains little explored. Object: To investigate the incidence of physical inactivity in individuals with heart disease after 12 months of SARS-CoV-2 infection. Methods: We prospectively evaluated 837 individuals who practiced regular physical exercise infected with SARS-CoV-2 in Rio Branco, Acre. Sociodemographic information, diseases of interest (cardiopathies, hypertension and diabetes mellitus) and details about the acute phase of the disease were collected after COVID-19 infection. In a second 12-month follow-up questionnaire, participants were asked about their physical exercise. To identify independent predictors of physical inactivity, multivariate logistic regression with stepwise strategy was used. Results: The mean age of the sample was 39 +- 11 years, 54% were male. A total of 14 participants were identified with heart disease (cardiac arrhythmia, n = 7; heart failure, n = 5; congenital heart disease, n = 1; third-degree atrioventricular block and pacemaker, (n = 1) and 42 participants with diabetes mellitus. A total of 243 (29%) participants were inactive after 12 months of SARS-CoV-2 infection. Compared to individuals without heart disease, those with heart disease had a higher occurrence of physical inactivity after 12 months of COVID-19 (28% vs 71%, respectively). After adjusting for multiple confounders, heart disease, diabetes mellitus, and female gender were predictors of long-term physical inactivity (figure 01). Conclusion: After 12 months of infection by SARS-CoV-2, 71% of patients with heart disease did not practice physical exercises. Female sex, diabetes mellitus and heart disease were independent predictors of long term physical inactivity. 111752 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Screening a Diagnosed Population with Systemic Arterial Hypertension and Diabetes Mellitus in the Amazon Riverside Community RAIMUNDO BENICIO DE VASCONCELOS NETO1, Gabriel Irismar Rodrigues Schwamback1, Rebecca Shaiane Soares Nunes Rivoredo1, Maria Eduarda Brotto de Souza1, Archimedes Fernandes Alves de Santana1, Julia Maria de Lourdes Balsan1, Sofia dos Santos Souza1, Renata Goncalves Silva Santos1, Izabella Gurgel do Amaral Pini1, Gesanaje da Paz Carvalho1, Fernanda Gabry Scazuza Gomes de Souza1, Byron Maia Feitosa1 (1) Centro Universitario Sao Introduction: Characterized as Chronic Non-Communicable Diseases (CNCD), Systemic Arterial Hypertension (SAH) and Diabetes Mellitus (DM) affect a large part of the Brazilian population, even if undiagnosed. Despite having different mechanisms of action, when associated, these CNCD considerably increase the risk of developing cardiovascular and renal pathologies. Therefore, assessing the prevalence of these comorbidities is necessary to establish intervention and management strategies for the population, especially in remote communities. Objectives: To estimate the prevalence of the association of Systemic Arterial Hypertension and Diabetes Mellitus in individuals living in a riverside community in the Western Amazon, Brazil. Methods: This is a cross-sectional, quantitative, retrospective study carried out with individuals aged between 1 and 87 years, regardless of gender, living in a riverside region in Porto Velho, Rondonia, Brazil. Home visits were carried out in which the residents answered an individual epidemiological questionnaire, each form had the information tabulated. Results: 268 individuals were randomly selected for the study, of which 55 (20.52%) had informed SAH, 26 (9.7%) had informed DM and 23 (8.58%) claimed to have both associated chronic non-communicable diseases. Females had the highest prevalence of the association between Systemic Arterial Hypertension and Diabetes Mellitus, with 14 cases (60.86%). The average age of individuals with both chronic non-communicable diseases is 58 years old. Conclusion: Systemic Arterial Hypertension and Diabetes Mellitus are the most frequent non-communicable chronic comorbidities in the world population. Nevertheless, the significant prevalence of these health conditions in the Amazon riverside population observed in this study reinforce the importance of monitoring cardiovascular health and associated risk factors. 111763 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Association between Subjective Sleep Quality and Peripheral and Central Blood Pressure Values of Patients in a Cardiology Clinic CLARISSA MARIA TITO BELTRAO1, Waleria Dantas Pereira Gusmao2, Alana Costa Machado Gomes1, Fernanda Abraham Leao1, Silvia Dandara Coutinho de Souza Lins Machado1, Giulia Abraham Leao1, Isabele Rejane de Oliveira Maranhao Pureza1, Annelise Machado Gomes de Paiva1, Marco Antonio Mota Gomes1, Claudia Roberta de Castro Moreno2 (1) Centro Universitario CESMAC; (2) Universidade de Sao Paulo Introduction: Blood pressure (BP) oscillations are regulated by neural, endocrine, endothelial and hemodynamic pathways in a circadian pattern. Although environmental and behavioral phenomena can mask the circadian rhythm of BP, circadian variability has higher levels in the morning, a plateau throughout the day and lower values at night during sleep. Poor quality or sleep deprivation can potentiate greater insulin resistance, chronic inflammatory processes, increased cortisol and catecholamines and exacerbation of stress, can disorganize the structure of the vascular wall, which can increase pressure. Objective: To determine if there is an association between subjective sleep quality and BP values. Methods: This is a cross-sectional study, carried out in a cardiology outpatient clinic, from Sep. to Dec. 2021, in which sociodemographic and clinical data were collected and a visual analogue sleep quality scale was applied through a structured questionnaire. Pressure values were estimated using an Arteris-AOP(r) oscillometric device. Results: 133 adults (19-89 years, mean 53.49 +- 14.01 years) were included in the study, 77.44% were female and 22.56% were male, the mean body mass index (BMI) was 29.30 +- 4.60 Kg/m2 (18.7-42.02 Kg/m2), the mean peripheral BP values were 128.51 +- 15.91 (99-181) mmHg of systolic BP, 83.05 +- 9.74 (62-115) mmHg of diastolic BP and 45.46 +- 13.55 (25-94) mmHg of pulse pressure. The BP central mean values were 118.63 +- 14.25 (116.19-121.08) mmHg of systolic BP, 84.62 +- 9.79 (64-116) mmHg of diastolic BP and 31.04 +- 11.25 (32.08-35.94) mmHg pulse pressure. To analyze the association between subjective sleep quality and peripheral and BP central values, linear regressions were performed with adjustment for age, sex and BMI. Subjective sleep quality was inversely proportional to systolic BP (b: -0.16; 95%CI: -2.76; -0.05; R2 = 0.19) and diastolic BP (b: -0. 28; 95%CI: -2.36; -0.59; R2 = 0.08), as well as systolic centrals BP (b: -081; 95%CI: -2.58; -0.20; R2 = 0.22) and diastolic centrals BP (b: -0.278; 95%CI: -2.35; -0.57; R2 = 0.08) with no effect on peripheral or central pulse pressure. The findings indicated an association between subjective sleep quality and peripheral BP levels in the studied population, that is, the worse the sleep quality, the higher the BP, constituting a promising area for study. Conclusion: Hypertensive patients should investigate sleep quality, since there is an association between poor sleep quality and high BP. 111932 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Financial Resources and Hospital Morbimortality from Chronic Rheumatic Heart Disease in Northern Brazil VANDO DELGADO DE SOUZA SANTOS1, Saul Rassy Carneiro1 (1) Universidade Federal do Para - UFPA Introduction: Chronic Rheumatic Heart Disease (RHD) is a sequela of rheumatic fever, which is a complication of pharyngotonsillitis caused by Streptococcus pyogenes and results from a late immune response to this infection in genetically predisposed populations, having a direct relationship with the development of services. of health in the country. All the financial resources made available to the Unified Health System are made directly by the National Health Fund (NHF) for each Federation Unit. Objectives: To relate the total financial transfers from the NHF and the amount of the Family Health Strategy (FHS) with the number of hospital admissions for RHD in northern Brazil from 2011 to 2020. Methods: This is a descriptive longitudinal epidemiological study based on secondary data from the Department of Informatics of the Unified Health System, the Portal of the National Health Fund of the Federal Government and the Portal of the Secretariat of Primary Health Care. RHD hospital morbidity and mortality data were correlated with the financial resources allocated to each FU and with the total number of FHS in each FU. Results: In the analyzed period, there were a total of 3.595 hospitalizations for RHD and a total of 336 deaths in the northern region, that is, a mortality rate of 9.35%. The state of Para had the highest rates of hospitalizations (38.58%), followed by the state of Amazonas (32.54%), and the state of Roraima had the lowest rates (0.39%). In the same period, Para and Amazonas were the ones that received the most financial transfers and had the largest number of FHS, and Roraima was the state that received the least financial resources and had the lowest number of FHS. Conclusion: The study showed that the greater the availability of NHF resources for the FU and the greater the number of FHS, the greater the hospitalization rates and, consequently, the mortality rate, this is due to the greater screening of heart diseases and greater access to health. 111777 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Profile of Myocardial Revascularization Procedures in the City of Vassouras for 10 Years SARA CRISTINE MARQUES DOS SANTOS1, Maria Luiza Silva Barbosa1, Alice Machado de Sales Silva1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: Myocardial revascularization surgery (CABG) is one of the treatments for obstructive atherosclerotic coronary artery disease accompanied by myocardial ischemia. The procedure can be performed with or without cardiopulmonary bypass (CPB). The present study aimed to analyze the current panorama of CRM procedures, with and without CPB and use of 1 or more grafts performed in the city of Vassouras for 10 years and correlate the current epidemiology with the results obtained. Methods: A systematic literature review and observational, descriptive and cross-sectional data collection of myocardial revascularization procedures, available at DATASUS - SUS Hospital Information System (SIH/SUS) for a period of ten years - December 2008 to December 2018 - evaluating the value of public spending, complexity, mortality rate, deaths, permanence, and character of care and articles available in Scielo, Lilacs, and PubMed. Results: In the analyzed period, 306 hospitalizations were observed for the performance of myocardial revascularization procedures, representing a total expenditure of R $ 3,228,341.33, with 2010 being the year with the highest number of hospitalizations (80) and 2011 being the year responsible for the largest amount spent during the period (R $ 687,969.79). Of the total procedures, 162 were performed on an elective basis and 144 on an urgent basis, with 306 being considered highly complex. The total mortality rate in the 10 years studied was 10.46, corresponding to 32 deaths, 2016 being the year with the highest mortality rate, 18.18, while 2012 had the lowest rate, 4.00. The mortality rate for elective procedures was 9.26 compared to 11.81 for urgent procedures. The average total hospital stay was 14.2 days. Conclusions: It can be seen, from the present study, that CABG is a procedure considered to be highly complex, regardless of whether it is performed urgently or not. A progressively considerably high mortality rate has been identified. Also, the need for correct notification of procedures is highlighted, aiming to improve the current epidemiological analysis. 111780 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION "Livres Do Tabaco", Helping Smokers to Quit Smoking and Getting to Know Their Profile in the Smoking Cessation Process BIANCA DE FATIMA PEREIRA1, Ramon Jose Moreira Silva1, Beatriz Stephan Farhat Jorge1, Pedro Drumond Maia1, Fernanda Silva Mota1, Gabriela Godinho Rezende1, Moises de Toledo Vilela1, Paula Gouvea Abrantes1, Marcela Rabelo1, Helio Brito de Lima Junior1, Eliane Ferreira Carvalho Banhato1, Arise Garcia de Siqueira Galil1 (1) Cardiology Department, Medical School, Federal University of Juiz de Fora, Juiz de Fora - Minas Gerais. Introduction: Smoking is a preventable and controllable chronic disease, in addition to high morbidity and mortality. Encouraging smoking cessation is a priority in Public Health and represents a cost-effective intervention. Objective: To describe the profile of smokers assisted by a treatment group for smoking cessation. Methodology: Longitudinal study, "Livres do Tabaco" group. Users with multimorbidities were assisted between September/2021 and March/2022, in consecutive treatment groups, mixed intervention (face-to-face and telemedicine), multidisciplinary team, behavioral cognitive approach sessions, drug treatment and follow-up. Definitions: Low level of schooling, <8 years. Normal systolic blood pressure (SBP) <130 mmHg. Depression, score Patient Health Questionnaire (PHQ-9) >=9 points. High risk for Obstructive Sleep Apnea Syndrome (OSAS), Stop Bang questionnaire >=5 points. Abusive use of alcohol, Audit-C >=5 points. Cognitive deficit, Montreal Cognitive Assessment <26 points. High nicotine dependence, Fagerstrom test >=5 points. Results: Sample with 36 patients, 6 consecutive treatment groups. Age, 56.6 +- 10.8 years; elderly, 44%; female, 66.70%; low level of schooling, 42.9%. Dyslipidemia, 52.90%; sedentary lifestyle, 61.5%; family history of coronary artery disease, 88.20%. Arterial hypertension, 68.6%; coronary insufficiency, 25.7%; diabetes mellitus, 17.1%; chronic obstructive pulmonary disease; 31.4%; previous history of cancer, 8.6%. High risk for OSAS, 31.4%, depression, 55.90%, cognitive impairment, 79.4%, alcohol abuse, 20%. Daily consumption of 17.9 +- 12.2 cigarettes; pack-years, 40.7 +- 29.3; high nicotine dependence, 68.6% and 55.6%, heavy smokers. Smoking triggers, stress, 85.7%; coffee, 60% and alcohol intake, 48.6%, were the most frequent. Smoking cessation until the 12th week of accumulated treatment, 33.3%. Conclusion: The initial data showed a high prevalence of both risk factors and comorbidities that most increase morbidity and mortality worldwide. It was also found a high prevalence of women, depression, cognitive impairment, in addition to high nicotine dependence and heavy smokers, data considered as weaknesses within the smoking cessation process. Even so, smoking cessation was observed to be within the average for smokers without associated comorbidities. 111783 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION Prototype of Electronic Stethoscope for Continuous Monitoring GUSTAVO PEDROZO1, Sergio Eduardo Soares Fernandes1, Pedro Henrique Santos de Medeiros1 (1) Escola Superior de Ciencias da Saude ESCS Introduction: Cardiac auscultation as a semiological tool has been widespread for more than four centuries, but only recently, with the popularization of computer processors, some of them with GPIO (General Purpose Input/Output) interfaces, it was possible to bring technological evolution to low-cost research centers. Objectives: To develop a low-cost cardiac and pulmonary audio signal capture prototype for future tests with continuous monitoring. Method: A long literature review was carried out about concepts of acoustics, stethoscope chest-piece modelling, sound signal capture and articles with similar prototypes of digital stethoscopes. Then, a chest-piece was built with Autodesk Inventor(r) software and printed with antimicrobial PLA (Polylactic Acid) filament. The prototype was assembled with a digital microphone INMP441(r) connected to a raspberry(r) pi 3b board (figure 1). The signal capture was performed using Python 3.10.4 code with pyaudio and mathplot libraries. The tests were carried out exclusively among the research team and validation tests about the method have not yet been carried out until this submission date. Results: The prototype was able to capture satisfactorily cardiac and pulmonary signals which were converted into phonograms (figure 1). The cost of materials used with the initial prototype was $67.32 including taxes and shipping. The cost proved that the reproduction of this prototype is viable for future larger tests. Likewise, it was possible to create new conceptual prototypes with potential for significant cost reduction, which will be produced in later phases of the study. Conclusion: The prototype allowed the analysis of production feasibility, however, to proceed the project with validation of methods for continuous monitoring, safety studies will still be necessary and, as well, the development of a continuous analysis code with intelligence to alert critical findings. This study allowed not only the production of a viable prototype, but also perspectives of cost reduction and the means for the continuity of the project with the validation of a monitoring system by auscultation. 111869 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Profile of Patients with Severe Heart Failure in a Tertiary Hospital in Salvador KARLA SANTOS PINTO1, Taina Viana1, Raissa Barreto Lima1, Ana Luisa de Aguiar Almeida Silva1, Eduarda Luciana Mendes Borges1, Larissa Xavier Gomes da Silva1, Aurea Maria Lago Novais1, Luiz Carlos Passos1, Mariana Barauna da Silva1, Elias Soares Roseira1, Karla Santos Pinto1, Joao Pedro Martins Moreira Granja1 (1) Hospital Ana Nery Introduction: Heart failure (HF) is a complex and highly prevalent clinical syndrome that limits the quality of life of many of its patients. Patients with heart failure reduced ejection fraction (HFrEF) are subject to higher mortality, given the potential reduction in cardiac function. The objective of this study is to describe the clinical and epidemiological profile of patients with HFrEF in a reference hospital in Salvador-BA. Methods: This is a prospective cohort that included patients with HFrEF treated at a heart failure outpatient clinic of a cardiology referral hospital in Salvador from September 2020 to July 2021. The outcome variables evaluated were mortality and hospitalization for any cause in 1 year. Variables with nonparametric distribution were described by median and interquartile range and categorical variables were described as frequency and percentage. Results: We included 196 patients with HFrEF with a median age of 60.5 (49-68) years, most of them men (54.1%), and a median LVEF of 29% (23-35). Ischemic and chagasic etiologies were the most prevalent, with 46 (23.5%) and 40 (20.4%) patients, respectively. Among the associated comorbidities, arterial hypertension (63.8%) and diabetes mellitus (30.6%) were the most observed. As for the medications in use, 93.9% of the patients used beta-blockers, 74% used ACEI/ARB, 13.3% used sacubitril/valsartan and 75% used spironolactone. After a 1-year follow-up, it was found that 25 (12.8%) patients died and 50 (25.5%) were hospitalized during the period. In the HF grading by the New York Heart Association (NYHA), 57 (34.5%) patients belonged to functional classes III-IV. Conclusion: The present study showed that the prevalence of HFrEF in the studied population reflects a considerable degree of hospitalization and death. It is expected that the results found can improve health policies that help in the care of patients with HFrEF, as well as in the prevention of unfavorable outcomes. 111788 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence of Diseases and Factors Associated with Cardiovascular Diseases in a Cardiology Ambulatory Service in the Brazilian Amazon: Evidence of a Potential Tool of Management in Primary Assistance ANNA LUIZA ALVES DE OLIVEIRA MIRANDA1, Matheus Vinicius Mourao Parente1, Daniel Chagas Barreto1, Jose Pedro da Silva Sousa1, Beatriz Siems Tholius1, Jose Wilker Gomes de Castro Junior1, Claudio Eduardo Correa Teixeira1, Fabiola de Carvalho Chaves de Siqueira Mendes1 (1) Centro Universitario do Estado do Para (CESUPA) Introduction: CardioVascular Diseases (CVD) are a public health problem, representing more than 30% of all deaths worldwide. In this context, evidencing the prevalence of the main diseases associated with CVDs and the profile of these patients is necessary, in order to guide the management of public health services that receive this demand. Objectives: In the present study, we aimed to highlight the prevalence of diseases and factors associated with CVDs in the population fraction admitted, via the Brazilian Unified Health System (Servico unico de Saude, SUS), at the Medical Specialties Center of the Para State University Center, in the city of Belem (Brazilian Amazon). Methods: A cross-sectional study was carried out based on the analysis of the medical records of patients seen at a Cardiology outpatient clinic for a period of 1 year. Results: Of 202 patients seen at the outpatient clinic, it was observed that 68.3% were female. Regarding the age group, the group between 55 and 64 years old predominated (29.2%), followed by those over 65 years old (28.7%). The main complaint reported by patients was chest pain (11.5%), followed by dyspnea (10.9%) and Systemic Arterial Hypertension (SAH, 10.45%). In addition, physical inactivity (23.8%), smoking (18.1%) and alcohol consumption (16%) were observed, which are important risk factors for CVD. Regarding family history, SAH (35%) stood out, followed by cancer (17.3%), Diabetes Mellitus (15.22%), Stroke (12.75%) and Acute Myocardial Infarction. (10.3%). Consistently and as expected from the results cited, the most common diagnoses among these patients were: SAH (31.8%), DM2 (7.7%) and Dyslipidemia (7.3%). The most prescribed drugs were Losartan (18.6%), Hydrochlorothiazide (13.3%) and Simvastatin (9.9%). The main tests requested were the echocardiogram (9.5%) and electrocardiogram (5.4%). Conclusion: We conclude that the observed frequency of diseases and factors associated with the development of CVDs is of significant prevalence, and such data should be valued and used as support tools in the management of public health services, especially in primary care. 111792 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hospitalization in the Public Health System in the Municipality of Sao Paulo Resulting from Hypertensive Diseases in the Year of 2021 GABRIEL RIBEIRO DE SOUZA1, Mayuri Akemi Rodrigues Higashi1, Rafaela Andrade Penalva Freitas2 (1) Universidade de Santo Amaro; (2) Instituto Dante Pazzanese de Cardiologia Introduction: In Brazil, arterial hypertension has a high prevalence and low control rate, being a risk factor for cardiovascular diseases, which implies large public health expenses related to hospitalizations resulting from complications. Objective: To quantitatively analyze the hospitalizations resulting from hypertensive syndromes in the city of Sao Paulo in the year 2021. Methodology: It consists of a descriptive, retrospective, longitudinal epidemiological study, based on the analysis of a econdary source of data, with the aim of the studies being hospital admissions in the Unified Health System of the city of Sao Paulo, in the year 2021, for causes related to diseases. Hypertensive as inclusion criteria, all hospital admissions were selected through the Hospital Information System (SIH), through DATASUS. The period studied was the year 2021. The morbidities were separated and selected according to the main hospitalization diagnosis and classified according to the International Disease Code 10 (ICD10), the following being selected: I10 - Essential hypertension, I11 - Hypertensive heart disease, I12 - Hypertensive kidney disease, I13 - Hypertensive heart and kidney disease, I15 - Secondary hypertension. Gender, race/color and age group were also taken into account. Results: During the study period, 2219 hospitalizations were performed for hypertensive diseases, of which 49.2% were male and 50.8% female. Among the target audience of the study, when considering race/color, 35.8% of patients consider themselves white, 8% black, 29.5% brown and 0.2% yellow. 26.5% of the registered admissions had no description of race/color. Regarding the age groups studied, there is a gradual increase in the number of hospitalizations as the observed age group also increases, with the group of patients over 80 years of age having the highest number of hospitalizations, corresponding to 14% of all the hospitalizations. Conclusions: Hospitalizations in the city of Sao Paulo due to hypertensive syndromes were slightly higher in males, most of whom were white and aged over 80 years. 111842 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING The Influence of Previous Acute Myocardial Infarction on Exercise Stress Echocardiography Results and Risk Factors, Among Chronic Coronary Syndrome Patients LARA TELES ALENCAR DUARTE1, Claudia Bispo Martins-Santos1, Jose Icaro Nunes Cruz1, Allexa Gabriele Teixeira Feitosa1, Gabriela de Oliveira Salazar1, Cleovaldo Ribeiro Ferreira Junior1, Danilo Brito Silva de Oliveira1, Victor Ravel Santos Macedo1, Eduardo Jose Pereira Ferreira1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe (UFS) Introduction: Considering the epidemiological relevance of Chronic Coronary Syndrome (CCS) and Acute Myocardial Infarction (AMI), studies that statistically associate the two groups with their main outcome, Myocardial Ischemia (MI), are still rare. Objective: To assess the occurrence of MI related to the presence or absence of previous AMI, among patients with CCS undergoing Exercise Stress Echocardiography (ESE). Methods: A cross-sectional study between January 2000 and January 2022 with individuals aged 40 years or older and with a positive history of CCS who underwent ESE at a cardiology referral service in Sergipe. A total of 1956 patients (X = 62 +- 9.6 years) were categorized according to the presence or absence of a history of previous AMI. Student's t test and chi-square test were used. A significance level of 5% was assumed. Analyzes were performed using SPSS Statistics software. Results: 735 patients (37.6%) with previous AMI and 1221 patients (62.4%) without the ischemic event were evaluated. There was no difference between the mean age of the groups. Male sex was associated with previous AMI (75.9% vs. 65.7%; p < 0.001), as well as diabetes (23.6% vs. 19.9%; p = 0.05) and dyslipidemia (76.7% vs. 71.2%; p = 0.008). On the other hand, statin use was positively associated with the group of patients without previous AMI (80.6% vs. 59.9%; p < 0.001). When the ESE results were analyzed, there was an association between MI (ischemia, fixed ischemia or fixed and induced ischemia) with the presence of previous AMI (71.8% vs. 41.4%; p < 0.001). However, an association was found between the result of new ischemia (ie, induced) and the group with no history of previous AMI (14.7% vs. 7.2%; p < 0.001). There was no significant difference between the distributions of: obesity (p = 0.207), arterial hypertension (p = 0.12), family history (p = 0.159), use of oral antidiabetics (p = 0.283) and the presence of symptoms (p = 0.261). Conclusions: MI in CCS patients was associated with patients with previous AMI in a fixed and fixed and induced manner, while new ischemia was associated with patients with no history of AMI. The relevance of statins as a protective factor for MI is also confirmed. 111802 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Analysis of Hypertensive Crisis Treatment in the Municipality of Vassouras in 10 Years SARA CRISTINE MARQUES DOS SANTOS1, Maria Luiza Silva Barbosa1, Alice Machado de Sales Silva1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: The hypertensive crisis is the rapid increase in systemic arterial pressure, which can occur in people with systemic arterial hypertension or those with normotension, potentially complicated with target organ damage. Divided into two categories, such as hypertensive urgency and hypertensive emergency. The present study aimed to analyze the current panorama of hypertensive crisis treatment procedures performed in the city of Vassouras for 10 years and to correlate the current epidemiology with the results obtained. Methods: A systematic review of the literature and an observational, descriptive and cross-sectional collection of hypertensive crisis treatment data, available at DATASUS - SUS Hospital Information System (SIH/SUS) for a period of ten years - December 2008 to December 2018 - evaluating the value of public spending, complexity, mortality rate, deaths, permanence, and character of care and articles available in Scielo, Lilacs, and PubMed. Results: In the analyzed period, there were 213 hospitalizations for the performance of hypertensive crisis treatment procedures, representing a total expenditure of R $ 82,593.96, 2009 being the year with the highest number of hospitalizations (66) and 2009 the year responsible for the highest amount spent during the period (R $ 28,385.62). Of the total procedures, 6 were performed on an elective basis and 207 on an urgent basis, with all 213 considered to be of medium complexity. The total mortality rate in the 10 years studied was 1.41, corresponding to 3 deaths, with the years 2008 and 2014 having the highest mortality rate, 9.09, while the year 2009 had the lowest rate, 1,52. The mortality rate for elective procedures was 0 compared to 1.45 for urgent procedures. Death cases covered only the years 2008, 2009, and 2014, with 1 death each. The average total hospital stay was 5.7 days. Conclusions: Low mortality was demonstrated, with seven cases in 10 years analyzed. It is worth noting the greater occurrence of hospitalizations on an urgent basis, highlighting the need for primary and secondary prevention, in addition to investing in early recognition by the patient. It is important to have correct notification of the procedures, aiming to improve the current epidemiological analysis. 111803 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Low Aerobic Capacity Predictors Under Physiological Stress Echocardiography LARISSA REBECA DA SILVA TAVARES1, Larissa Rebeca da Silva Tavares1, Claudia Bispo Martis-Santos2, Irlaneide da Silva Tavares2, Jose Icaro Nunes Cruz2, Gabriela de Oliveira Salazar2, Silvia Regina Freire Oliveira Melo3, Lais Oliveira Melo1, Stephanie Macedo Andrade4, Antonio Carlos Sobral Sousa2, Joselina Luzia Menezes Oliveira2, Diego Henrique da Silva Tavares1 (1) Universidade Tiradentes - UNIT; (2) Universidade Federal de Sergipe - UFS; (3) Hospital Primavera; (4) Hospital Sao Lucas Introduction: The metabolic equivalent intensity levels (MET) are a way of expressing cardiorespiratory fitness (CRF). High risk cardiovascular profiles are related to low aerobic capacity. Objective: To evaluate low cardiorespiratory fitness under stress during Physiological Stress Echocardiography (PSE). Methods: Transversal study between January 20000 and January 2022 with individuals who have been through PSE at a cardiology reference service. 3894 Patients were categorised (57 +- 11 years) under low (MET < 7,9), intermediary (7,9 <= MET < 10,9) or high (MET >= 10,9) CRF. The chi-square test and multinomial logistic regression were used with the SPSS Statistics software version 22.0. Admitting a significance level of 5%. Results: In the sample, 56.5% (2202) were female; 25.7% (1002) had low CRF, 33.5% (1306) intermediate and 40.7% (1586) high CRF. The comparison between high and low CRF groups show that older age (OR = 1.126; 95%CI = 1.113-1.139; p < 0.001), arterial hypertension (OR = 1.886; 95%CI = 1.501-2.369; p < 0.001), diabetes mellitus (OR = 1.447; 95%CI = 1.043-2.007; p = 0.027), obesity (OR = 1.936; 95%CI = 1.496-2.506; p < 0.001), sedentary lifestyle (OR = 3.18; 95%CI = 2. 55-3.966; p < 0.001), alcoholism (OR = 1.781; 95%CI = 1.387-2.286; p < 0.001) and segmental alteration during exertion (OR = 2.127; 95%CI = 1.562-2.896; p < 0.001) were predictors of low CRF. When compared to the intermediate CRF group, older age were predictors of low CRF (OR = 1.069; 95%CI = 1.058-1.08; p < 0.001); sedentary lifestyle (OR = 1.614; 95%CI = 1.32-1.975; p < 0.001), alcoholism (OR = 1.499; 95%CI = 1.177-1.908; p = 0.001), obesity (OR = 1.35; 95%CI = 1.076-1.694; p = 0.009) and segmental alteration during exertion (OR = 1.526; 95%CI = 1.168-1.996; p = 0.002). Male sex protected against low CRF in comparisons to the intermediate (OR = 0.491; 95%CI = 0.390-0.618; p < 0.001) and high cardiorespiratory fitness (OR = 0.164; 95%CI = 0.128-0.209; p < 0.001) groups. Conclusion: When evaluating patients with low CRF, older age, sedentary lifestyle, obesity, alcohol consumption and segmental alteration on exertion were predictors. The predictive model also showed that physical inactivity increased the chance of low CRF by three times, being the main predictor. 111809 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Profile of Transvenous Defibrillator Cardioverter Implant Procedures in Brazilian Regions for 10 Years SARA CRISTINE MARQUES DOS SANTOS1, Maria Luiza Silva Barbosa1, Alice Machado de Sales Silva1, Ivana Picone Borges de Aragao1 (1) Universidade de Vassouras Introduction: The defibrillator cardioverter implantation is intended to diagnose and treat rhythmic heart changes, preventing death. It is a minimally invasive and fast recovery procedure. The objective was to analyze the current panorama of single-chamber and transvenous double-chamber defibrillator implant procedures performed in Brazil and correlate the current epidemiology with the results obtained. Methods: A literature review and observational, descriptive, and cross-sectional collection of single-chamber and transvenous double-chamber cardioverter implant data, available at DATASUS - SUS Hospital Information System (SIH/SUS) - December 2008 to December 2018. Results: In the period analyzed, there were 10,736 hospitalizations for performing single-chamber and transvenous double-chamber cardioverter implantation procedures, representing a total expense of R$ 428,781,939.15, 2018 being the year with the highest number of hospitalizations (1,238) and the highest amount spent (R$ 54,823,826.53). The total mortality rate in the 10 years studied was 0.46, corresponding to 49 deaths, with 2008 being the year with the highest mortality rate, 3.17, while 2018 had the lowest rate, 0.24. The region with the largest number of hospitalizations was the Southeast with 4,837 hospitalizations, followed by the South with 2,570, the Northeast with 1,728, the Midwest with 1,434, and, finally, the North with 167 hospitalizations. The region with the highest number of deaths was the Southeast with 22 cases, while the North region had the lowest number, with 3 registered deaths. The northern region had the highest mortality rate (1.80) and the southern region had the lowest rate, with a value of 0.35. Conclusions: It can be observed from the present study that this is a procedure with a considerably low mortality rate with a progressive reduction in the period of 10 years from 2008. It is worth noting that the northern region despite having the lowest incidence of performing the procedure has the highest mortality rate. 111813 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Comparison of Mortality Rates between Treatments for Acute Myocardial Infarction: Angioplasty and the use of Fibrinolytic LUIZ FELIPE SILVA MARCIAO1, Mateus Itiro Tamazawskas Otake2, Micaella Yanne Fender Lobato2, Leonardo Barbosa Duarte2, Nyara Rodrigues Conde de Almeida3, Victor Matheus Mendonca de Araujo2, Rafael Silva Lemos2, Livia Guerreiro de Barros Bentes2, Danusa Neves Somensi2, Herick Pampolha Huet de Bacelar2, Edmundo Frota de Almeida Sobrinho2, Deivid Ramos dos Santos2 (1) Centro Universitario do Estado do Para; (2) Universidade do Estado do Para; (3) Universidade Federal do Para Introduction: The most serious representative of acute coronary syndromes is acute myocardial infarction, which is an extremely serious complication caused by the interruption of blood flow to the myocardium. Therefore, the therapeutic objective is arterial clearance and cardiac reperfusion; for this, there is the use of fibrinolytic and/or angioplasty, the therapeutic methods can be used exclusively or associated, depending on the patient's clinic and the time of Evolution. Objective: To analyze the mortality rate between Coronary Angioplasty and Catheter-Directed Thrombolysis with fibrinolytic procedures in Brazil in the period 2011-2021. Methods: It is characterized as descriptive, quantitative, and retrospective performed by collecting data from the Hospital Information System of the Unified Health System (SIH/SUS-DATASUS) during May 2022. Data were organized according to the procedure performed in the Microsoft Excel program. Results: In the period from 2011 to 2021, 33.867 Coronary Angioplasty (CA) surgeries were performed, with the Southeast region having the largest number of procedures performed (41.6%), in addition to an average annual growth rate (AAGR) of 3.4% between 2011-2016 and an annual decrease of 2.2% between 2016-2021. Furthermore, 2.179 deaths were associated with the procedure, and the mortality rate (MR) was 6.42 +- 1.32. For the Catheter-Directed Thrombolysis with fibrinolytic (CDT), 1168 were performed between 2011 and 2021, with an AAGR of 26.8% between 2011-2016 and 1.7% between 2016-2021, and the majority in the Southeast (51.7%). There were 49 deaths recorded in this period and an MR of 4.17 +- 2.11. Therefore, for CA, the number of deaths in 2011 was 126, in 2016 it was 205, and in 2021 it was 243, with an AAGR of 10.2% between 2011-2016 and 3.5% between 2016-2021. Regarding CDT, for the same variable, 3 records in 2011, 6 in 2016, and 2021 were 7 deaths, with an AAGR of 14.9% between 2011-2016 and 3.1% between 2016-2021. Both procedures showed an increase in deaths in the number of deaths vs a number of procedures, with emphasis on the correlation made in the CA, where the increase did not follow the decrease of the last five years, in addition to the fact that the MR was higher in the CA compared to CDT. Conclusion: The Southeast region had the highest number of CA and CDT procedures performed in the period evaluated. In addition, a higher MR was observed for CA when compared to CDT and a decreasing AAGR between 2016-2021. 111815 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR IMAGING Percutaneous Treatment with Coronary Stents Guarantees Patients with Previous Acute Myocardial Infarction Better Conservation of Echocardiographic Parameters at Rest and During Exercise LARA TELES ALENCAR DUARTE1, Jose Icaro Nunes Cruz1, Claudia Bispo Martins-Santos1, Allexa Gabriele Teixeira Feitosa1, Gabriela de Oliveira Salazar1, Cleovaldo Ribeiro Ferreira Junior1, Andre Pinheiro Zylberman1, Edvaldo Victor Gois Oliveira1, Eduardo Jose Pereira Ferreira1, Antonio Carlos Sobral Sousa1, Enaldo Vieira de Melo1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe (UFS) Introduction: Chronic Coronary Syndrome (CCS) appears frequently to clinical cardiologists, but the literature still lacks data on the evolution of its complex pathology. Objective: To analyze, by Exercise Stress Echocardiography, the behavior of myocardial ischemia in CCS patients with previous Acute Myocardial Infarction (AMI), according to the given treatment. Methods: A cross-sectional study from January 2000 to January 2022 with individuals aged >= 40 years (X = 62 +- 9.6 years) who underwent the exam at a cardiology referral service in Sergipe. They were grouped by the intervention performed after the AMI: surgical revascularization, Stent, or clinical treatment. Patients with CCS with no history of AMI were also considered. The behavior of the left ventricle was evaluated considering the Left Ventricular Mass Index (LVMI) and the Ejection Fraction (EF) while the behavior of the myocardial ischemia, considering the Wall Motion Score Index (WMSI). Chi-square test and one-way ANOVA analysis for multiple comparisons with Tukey's post-hoc were used. The significance level was set to 5%. Analyzes were performed using SPSS Statistics. Results: 727 patients (37.3%) with previous AMI were studied: 142 (7.3%) underwent surgical revascularization, 284 (14.6%), Stent, and 301 (15.5%), clinical treatment. 1221 patients (62.7%) without previous AMI were evaluated. On average, the increase in LVMI was greater among those who received only clinical treatment, compared to those who had no previous AMI (108g vs. 91.3g; p = 0.010); the other groups showed no significant difference. Regarding EF, individuals treated with surgical revascularization (14.4% vs. 3.5%; p < 0.001), with Stent (10.8% vs. 3.5%; p < 0.001) and clinically (9.5% vs. 3.5%; p < 0.001) had a higher percentage of reduced EF compared to patients with CCS without previous AMI. As for resting and exercise WMSI, the surgical revascularization group (averages 1.21 and 1.22 respectively) and the clinically treated group (averages 1.17 and 1.20) were statistically different from the Stent group (averages 1.11 and 1.10) (p < 0.001) and the SCC group without previous AMI (averages 1.04 and 1.05) - those last also different among themselves. Conclusions: In the stratification of patients with CCS with previous AMI, treatment with the Stent showed better evolution in the behavior of the LVMI, EF and WMSI on the Exercise Stress Echocardiogram at rest and exercise, when compared to patients with CCS without previous infarction. 111819 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Myocarditis Related to Vaccine Against COVID-19 in Adults VITORIA CALDAS GONCALVES1, Beatriz Caldas Goncalves2, Ana Elisa Caldas Goncalves3, Gabriela Magalhaes Bandeira Gomes1, Isadora Vilela Rodovalho1, Rodrigo Rodrigues Pache4, Ana Luiza Espindula Rocha1, Paulo Henrique Rodrigues1 (1) Universidade Evangelica de Goias - UniEvangelica; (2) Universidade Federal de Goias - UFG; (3) Universidade Federal de Uberlandia - UFU; (4) Universidade Federal do Tocantins - UFT Introduction: The mRNA vaccines developed against the SARS-CoV-2 virus, despite being well tolerated in most cases, are related to serious and potentially fatal reactions, such as myocarditis. This is characterized as an inflammation of the heart muscle resulting from the action of toxins, through hypersensitivity reactions or by an autoimmune mechanism. In order to reduce clinical complications and improve functional prognosis, diagnosis and treatment must be performed quickly and accurately. Objective: To understand the development of myocarditis as an adverse effect of the vaccine against the SARS-CoV-2 virus, as well as its main prognostic aspects. Methods: This is an integrative review with a search in the databases PubMed and The Virtual Health Library (VHL) using the Health Sciences Descriptors "myocarditis", "covid-19" and "vaccine", combined with the boolean operator AND. We selected 10 original articles, whose inclusion criteria consisted of recent publication date (last 5 years) and languages in Portuguese and English. Results: With regard to immunization against COVID-19, myocarditis should be suspected when symptoms of heart failure such as progressive chest pain, dizziness, fever, nausea and vomiting begin about five days after vaccination. It is common the elevation of cardiac biomarkers in the complementary exams, such as troponin I, in addition to evidence of changes in ventricular repolarization on the electrocardiogram. Typically, an increase in the plasma concentration of N-terminal pro-B-type natriuretic peptide (NTproBNP) and C-reactive protein (CRP) is found. A possible pathophysiological justification for the relationship studied is the fact that cardiac myocytes express ACE2 receptors, which can bind to the spike glycoprotein, translated from the mRNA vaccine, and trigger cardiac complications. However, there is still not enough evidence to establish this causal association. Conclusion: Myocarditis after vaccination against COVID-19 usually follows a benign course; however, medical monitoring is necessary due to the high rate of morbidity and mortality, even though it is an infrequent and poorly understood adverse effect. It is important to note that the benefits of vaccination outweigh the risks of developing myocarditis since COVID-19 infection carries a much higher rate of acute and chronic cardiovascular sequelae, including arrhythmias and thromboembolic events. 111827 Modality: E-Poster Scientific Initiation - Non-case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Impact of Diabetes Mellitus in Young Individuals with Acute Coronary Syndromes on Cardiovascular Outcomes and the Direct and Indirect Health-Related Costs MARIANA GUIMARAES SOUZA DE OLIVEIRA1, Ana Carolina Augusto Rocha1, Eduardo Souza Amancio da Costa1, Marina Miguel de Lucena1, Alexandre Anderson de Souza Munhoz Soares2, Luiz Sergio Fernandes de Carvalho3 (1) Universidade Catolica de Brasilia UCB; (2) Instituto Aramari Apo; (3) Clarity Healthcare Intelligence Objectives: We seek to compare the prevalence of diabetes (DM) and cardiovascular outcomes (CO) associated with groups of young individuals who presented their first acute coronary syndromes (ACS) with ages <55 y/o (Premature ACS, pACS). In parallel, we sought to comprehend the economic impact of the pACS and DM association. 2. Methods: We analyzed the registers retrospectively with the first ASC aged <55 y/o from 2013 to 2015 within the B-CaRE:QCO study, a registry that includes all the admissions to public hospitals of Federal District, Brazil. DM has been defined as hemoglobin A1c >6.5%, documented diagnostics, or the reception of diabetes treatment. Cause of death was adjudicated and all cause-specific hospitalizations were retrieved from digital records. The primary outcome was overall health care spending (sum of the cost of lost productivity [CLP], ambulatory costs, and the cost of recurrent hospitalizations [CRH] in international dollars [Int$] per year), and the secondary outcomes were the mortality due to all causes of the recurrent ACS. 3. Results: Among 6,341 individuals with ACS, 2.242 were pACS (mean age 47.9 +- 5.5 years), diabetes was present in 514 individuals (29.7%), of whom 137 (27%) used insulin. During median follow-up of 6.5 (IQR 1.9) years, DM was associated with higher all-cause mortality (HR 1.58[95%CI 1.3-1.9]; p < 0.001) and recurrent ACS (1.48[95%CI 1.3-1.7]; p < 0.001) relative to young and non-diabetic individuals. These associations persisted after the adjustment for baseline covariates (all-cause mortality: 1.69; p = 0.003; recurrent ACS: 1.72; p < 0.001). Compared to older individuals, the pASC group had lower all-cause death rates (p < 0.001), but higher rates of recurrent ACS (p = 0.012) during the monitoring, particularly in diabetics. Driven primarily by CRH and CLP, young people with diabetes spent the highest amounts (Int$16,350 [12,545-23,740]/year in pACS+DM+ vs Int$14,555[12,593-20,354]/year in prACS+ Int$12,183 [10,082-17,416]/year in older individuals, p < 0.001). 4. Conclusions: Diabetes was present in 29.7% of patients presenting ACS at age <55 y/o and was associated with higher all-cause mortality at long-term as well as a more recurrent ACS in comparison to young non-diabetic individuals, but otherwise lower when compared to older individuals. However, young diabetics have shown the highest overall healthcare expenditures. These findings highlight the need for implementation of heftier therapies aimed at preventing. 111834 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Characteristics and Prognosis of Patients with Acute Heart Failure According to the Universal Ejection Fraction Classification MICHELLE BOZKO COLLINI1, Gustavo Sarot Pereira da Cunha1, Leonardo Henrique dos Santos de Melo1, Matheus Bissa Duarte1, Jorge Tadashi Daikubara Neto1, Rafael Moretti1, Carolina Ruschel Senger1, Karoline Cordeiro Vercka1, Jessica Tamires Reichert1, Lucas Muller Prado1, Jamilly Giuriatti Anziliero1, Miguel Morita Fernandes-Silva1 (1) Universidade Federal do Parana Introduction: The universal classification of heart failure defined four classes according to the ejection fraction (EF). These classes have different characteristics and prognosis in chronic patients, but the information in the literature on acute heart failure is scarce. Objectives: To compare the prognosis of the EF classes in patients admitted for acute heart failure. Methods: We studied patients admitted for acute heart failure in a tertiary hospital in Curitiba, Brazil, from October 2019 to July 2021. EF classes were defined as: reduced EF (HFrEF): EF <=40%, mildly reduced EF (HFmrEF): EF 41-49%, preserved EF (HFpEF): EF >=50% and improved EF (HFimpEF): baseline EF <=40%, with >=10 point increase from baseline, and a second measurement of EF >40%. The outcome was all-cause mortality in a six-month follow-up. Results: From 153 patients (67.21 +- 14.86 years, 50.3% female, EF = 43.79 +- 17.62%), 52% had HFrEF, 33% HfpEF and 12% HFmrEF. The proportion of patients with HFimpEF was very small (3%). As expected, HFrEF patients were mostly male (66.2%) and more likely to have an ischemic etiology (42.5%); and HFpEF patients were more likely female (67.3%), and had hypertension (90.9%) and atrial fibrillation (49.1%), as compared with the other categories. The 6-month survival rate did not significantly differed among the EF classes (p = 0.55) (figure 1). Conclusions: In patients with acute heart failure, the proportion of HFimpEF was small and the 6-month all-cause mortality was similar among the EF classes. 111837 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Prevalence of Arterial Hypertension in a Community Riverside of the Rio Jamari in the Amazon ANA CAROLINE LEITE GUEDES1, Maria Eduarda Brotto de Souza1, Fernanda Dias de Oliveira1, Roberta Cristiane Oliveira da Silva1, Gesanaje da Paz Carvalho1, Jade Gomes da Costa Medeiros1, Caroline de Souza Alovisi1, Ana Julia Omodei Rodrigues Martim1, Renata Goncalves Silva Santos1, Lucas Vieira Amorim1, Sofia dos Santos Souza1, Fernanda Gabry Scazuza Gomes de Souza1 (1) Centro Universitario Sao Introduction: Systemic arterial hypertension (SAH) is a multifactorial condition, which depends on genetic/epigenetic, environmental and social factors, characterized by persistent elevation of blood pressure (BP). The diversity of causes for the development of SAH is extensive and, in most cases, it is associated with alcoholism, smoking and physical inactivity, in the entire population, with a special focus on remote communities. The health of the Amazon riverside population has been the focus of special attention, mainly related to factors such as changes in the level of physical activity in their daily lives (fewer active individuals) due to the so-called "facilities" of the modern world, and changes in their patterns of physical activity. In this way, the present work aims to analyze the prevalence of this comorbidity in riverine people and highlight the relevance of the problem. Objectives: To describe the prevalence of SAH in a riverside community on the Jamari River in the Amazon, Brazil. Methods: The present work is a cross-sectional and quantitative cohort study, through the application of a questionnaire to the population, between the ages of 1 to 87 years, residents of the region corresponding to the district of Sao Carlos do Jamari, in Rondonia. The collected data were described and tabulated for further analysis. Results: 269 individuals from the region in question were randomly and unintentionally selected. Of these, 78 people (29%) reported having Systemic arterial hypertension, among them the highest prevalence for women. Social habits include drinking (15.3%) and smoking (10%), as well as unspecified heart problems (10%). Conclusion: The aforementioned study brings the discussion about the prevalence of SAH in riverside populations in the Amazon, which presents an expressive percentage, with an association of multiple factors, proving the necessary detailed analysis of the situation aiming at reducing risks and improving the population's quality of life. 111841 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION Accuracy of Cardiac Arrhythmias and Conduction Disorders Diagnosis using a Smartwatch GUILHERME NUNES MIRANDA1, Daniel Italiano de Araujo Filho1, Francisco Jose de Almeida Cruz Junior2, Hermano Rodrigues Pinheiro3, Maria Clara Almeida4, Carlos Eduardo Batista de Lima2 (1) Universidade Federal do Piaui; (2) Hospital Universitario do Piaui; (3) Centro de Pesquisa Cardiolima; (4) Instituto do Coracao - FMUSP Introduction: Implantable devices increase the detection of silent atrial fibrillation in high-risk populations, being a useful tool in the early diagnosis of these patients, allowing monitoring for a longer time. The Smartwatch could be a useful, easy tool for the daily cardiological propaedeutics. However, there is just a little information on the limitations of analysis on the watch's Electrocardiogram (ECG) in comparison to the conventional one. Objective: To analyze, in patients with cardiovascular disease, the electrocardiographic aspects detected from the device in comparison to the conventional ECG, identifying aspects of similarity between the tracings. Method: A cross-sectional observational study of diagnostic accuracy is currently being carried out in a Hospital since July 2021. Each patient did three ECGs, ECG 1 = 12-lead conventional; ECG 2 = rhythm strip DI single lead conventional; ECG 3 = DI single lead on the smartwatch. The ECGs were randomly delivered for 3 cardiologists, the 3 examiners were blinded. The data was analyzed comparatively between the 3 measures in each patient and between each other. Data were analyzed using the Statistical Package for the Social Science program (SPSS(r), version 20.0). For statistical analysis, the Kappa statistics, ANOVA test, Turkey post-test were used, considering a significant p-value <0.05. Results: 19 patients were analyzed between July 2021 and April 2022. Fifty five ECGs were collected and the 3 examiners registered a total of 165 reports. The average age was 61,68 and male gender was more prevalent (78,9%), the most common diseases were angina (57,9%) and Atherosclerosis (57,9%). The results showed the sinusal rhythm detection Kappa between examiners 1, 2, 3 in the Smartwatch's ECG were (0,799; 0,895; 0,712) and the sinusal rhythm detection Kappa in the conventional 12-lead ECG were (1,000; 1,000; 1,000). Some data showed that the Smartwatches ECG's could detect abnormal rhythms, even when we could not specify, nonspecific changes in ventricular repolarization (AIRV) were detected. Conclusions: In this 19 patient analysis, the Smartwatch has shown a good accuracy to detect if the patient had a normal rhythm. Even though the wereables presented some data capture limitations but, as we educate patients on how to use the 1-lead ECG, add more data and new technologies in each patient analysis, it could be a useful tool for monitoring and possible early diagnosis of abnormalities, such as arrhythmia. 111848 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION Association of Wearable Devices and Cardiovascular Risk Reduction ANA ELISA BARRETO CALIXTO1, Ana Elisa Barreto Calixto1, Guilherme Rufino Marques Pellegrin1, Nathalia Noyma Sampaio Magalhaes1, Luiza Dahbar Rodrigues1, Matheus Pericles Belcavello1, Patrick Ribeiro Reis1, Lucas Nicolato Almada2 (1) Faculdade de Ciencias Medicas e da Saude de Juiz de Fora - Suprema; (2) Hospital e Maternidade Therezinha de Jesus - HMTJ Introduction: Cardiovascular diseases are the leading cause of death globally. They are preventable by changing risk behaviors, such as a sedentary lifestyle and poor sleep quality. The implementation of low-cost technology-based interventions can contribute not only to improve health outcomes, but also to reduce public health costs related to cardiovascular disease. Wearable devices (WD) are gadgets that can be worn anywhere on the body, allowing the generation of data on physical activity, heart rate and rhythm and, more recently, impedance and thoracic fluid data. The assessment of these data is an important challenge in the clinical setting. Objectives: To evaluate the impact of WD, associated with physical exercises, in reducing cardiovascular risk. Methods: Literature review was carried out in the MedLine database using the descriptors: "Wearable Devices", "Cardiovascular Risk" and their variations according to MeSH. Controlled and randomized clinical trials carried out in humans and published in the English language in the last 10 years were included. The PRISMA scale was used to improve the reporting of this review. Results: Two studies analyzed the outcomes of WD in patients with elevated cardiovascular risk. In the first one, 144 patients with a mean age of 61 years were recruited. 70 patients participated in the experimental group (EG) and, as an intervention, they used WD, resulting in a significant increase in the number of steps and activity level over time (p < 0.001 and p = 0.01, respectively). No significant changes were observed in blood pressure, weight, and sleep quality. In the second study, 40 individuals with a mean age of 72 years were randomized into two groups. Both of them received instructions concerning physical activity practice, but the EG also received WD. 12 weeks after randomization, the EG presented a significant increase in the number of steps (p < 0,05) while in the control group (CG) this number actually decreased. In EG, there was a reduction of 4 mmHg in blood pressure levels and the CG suffered an increase in this parameter. Sedentary behavior did not suffer any alteration in either group. Conclusion: The results of the studies showed that the reduction of cardiovascular risk was optimized by the association of WD with regular practice of physical activities, which suggests that the use of these devices has the potential to help in the prevention and treatment of cardiovascular diseases. 111865 Modality: E-Poster Scientific Initiation - Non-case Report Category: NUTRITION Effects of Energy Drinks on the Cardiovascular System and Their Long Therm Repercussions GABRIEL JUNQUEIRA JULIO1, Giuliano Fernando da Silva Julio2, Sofia Sousa Alexandre1, Katarina Masciano Pereira1, Sevana Valadao Naves1, Danilo Cezar Aguiar de Souza Filho1, Douglas Araujo Menezes Filho1, Renato Tassi de Lima1, Isadora Silva de Sousa1, Lorena Costa de Holanda1, Giovanna Cristina Silveira Correa1, Mariana Mello Menezes1 (1) Centro universitario euro americano - UNIEURO; (2) Prevencor Introduction: The increased consumption of energy drinks (ED) in recent years has encouraged studies with the purpose of identifying possible damage caused by indiscriminate and prolonged use. The increase in consumption is associated with the intention to improve performance in daily activities. The compounds present in ED show that the levels of caffeine and sugar ingested can generate cardiovascular, behavioral and metabolic repercussions when used for a long time. Objectives: Acknowledge the risks of indiscriminate consumption of abusive doses of ED and the effects caused by the chronicity of use. Methodology: A systematic literature review was performed. In data collection, a bibliographic and documentary search was carried out on the subject, using articles that discuss the cardiovascular repercussions associated with the use of energy drinks. The search platform was PubMed, using the terms "energy drink" and "cardiovascular" as descriptors. 16 articles were selected, and the selection criteria were free systematic review studies or clinical trials, with 5 years of publication, in English or Portuguese, the articles that didn't match the theme were eliminated. For analysis, the different results of the studies were systematized and compared. Results: When comparing the studies, it was found that the abusive use of ED increases the probability of cardiovascular repercussions such as tachycardia, arrhythmia, ischemia, increased systemic blood pressure, changes in repolarization, conduction disturbances and prolongation of QT intervals on the electrocardiogram. In addition to behavioral changes, such as stress, increased anxiety attacks and insomnia. The metabolism is altered by elevated cortisol levels and increased sugar consumption, providing greater risk for developing type 2 diabetes mellitus. Caffeine is the main compound that influences the perceived changes and its association with alcoholic beverages generates more serious and faster-evolving repercussions. Conclusion: The effects of the use of ED are already present in the studies carried out and show consequences in the lives of users who often don't have the necessary knowledge about the drink and its long-term damage remains uncertain. Thus, the cardiovascular and metabolic systems are affected, but also the psychological system undergoes negative changes, demonstrating the need for studies with longer follow-up. 111907 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Mortality Predictors in Patients with Heart Failure in a Referral Hospital KARLA SANTOS PINTO1, Raissa Barreto Lima1, Ana Luisa de Aguiar Almeida Silva1, Eduarda Luciana Mendes Borges1, Elias Soares Roseira1, Livia Maria Goes Lemos1, Aurea Maria Lago Novais1, Beatriz Barbosa Viana1, Joao Pedro Martins Moreira Granja1, Karla Santos Pinto1, Larissa Xavier Gomes da Silva1, Clara Salles1 (1) Hospital Ana Nery Introduction: Chronic heart failure is a condition associated with high rates of morbidity and mortality. Despite recent advances in optimized drug therapy for patients with reduced ejection fraction (HFrEF), they still have a significant risk of death. Therefore, the objective of this study is to identify predictors of death among individuals with HFrEF in a referral hospital in the city of Salvador, Bahia. Methods: This is a prospective cohort of patients with HFrEF, treated at a heart failure outpatient clinic from September 2020 to July 2021. The outcome variables evaluated were mortality and hospitalization for any cause in one year. For data analysis, the Odds Ratio (OR) was used as a measure of association between categorical variables and 95% Confidence Intervals (CI), using the chi-square test in the bivariate analysis. Continuous variables with normal distribution were compared using Student's t test. Multivariate analysis with logistic regression was used to assess independent predictors of mortality. A value of p < 0.05 was considered for statistical significance. Results: We included 196 patients with heart failure with a median age of 60.5 (49-68) years, most of them men (54.1%) and a median LVEF of 29% (23-35). Ischemic and chagasic etiologies were the most prevalent, with 46 (23.5%) and 40 (20.4%) patients, respectively. After 1 year of follow-up, it was found that 25 (12.8%) died, 50 (25.5%) were hospitalized and NYHA III-IV totaled 57 (34.5%) patients. Most patients who died were male (64%) and 49% had a history of hospitalization <1 year. In the multivariate logistic regression model, Chagas' etiology remained the only independent predictor of mortality (OR 1.36; 95% CI 1.52-10.11; p = 0.005). In the univariate analysis, the mortality predictors were: DM2, CAD, hospitalization <1 year and Chagas' etiology (Table 1). Conclusion: Chagas' etiology was the only independent predictor of mortality in patients with HFrEF. 111875 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT The use of Colchicine in Acute Myocarditis - A Systematic Review EDUARDA CORREA MAIA1, Evandro Tinoco Mesquita1 (1) Universidade Federal Fluminense Fundamentals: Myocarditis is an inflammation of the myocardium that can affect cardiac function, reducing ejection fraction and causing arrhythmias, leading to heart failure syndrome, cardiogenic shock and sudden death. This condition can be caused by a viral infection, an immune-mediated response due a late viral response, inflammatory autoimmune diseases or an auto-inflammatory response, making myocarditis even more relevant within the COVID-19 pandemic. Colchicine is a low-cost anti-inflammatory, already known and used in rheumatologic diseases, and, now, used in cardiology for pericarditis and coronary disease. In cases of colchicine use for myocarditis there have been publications with positive results, however its effects in patients with acute myocarditis are not clearly demonstrated. Goal Systematically review the literature to assess the effects of colchicine use in patients with acute myocarditis. Methods: We performed a systematic review of the effects of colchicine in patients with myocarditis. Case series, randomized studies and case controls published on PubMed, SciELO and Google Scholar platforms were selected, from January 2010 to January 2022, in Portuguese, English, Spanish and French. Results: Initially, a total of 62 studies were found. After exclusions, 30 articles remained, with a total of 128 patients with acute myocarditis who used colchicine. Of this group, 10.93% (14 patients) had myocarditis in association with another disease, 3.9% (5 patients) in association with autoimmune diseases, and 16.4% (21 patients) with myopericarditis. In the only study using a control group consisting of 60 patients (didn't use colchicine), 31.6% (19 patients) had complete resolution of symptoms. In the end, a positive association was demonstrated in the use of colchicine in the treatment of myocarditis, with 75.78% (97 of 128 patients) of patients presenting resolution of symptoms within 14 months after starting treatment. Conclusion: The results found in this systematic review, so far, suggest that the use of colchicine in the treatment of acute myocarditis has been effective. The study also showed the absence of randomized studies that analyze the effectiveness of colchicine in cases of acute myocarditis, with only one study using a control group and showing significant improvement in the clinical picture. In addition, the little evidence related to cases of post-covid myocarditis is even more relevant in the current pandemic context. 111897 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM COVID-19 Cardiovascular Outcomes in People Living with HIV in Brazil MANUELA FURTADO SACIOTO1, Thais Lorenna Souza Sales2, Joao Victor Baroni Neves1, Vivian Costa Morais de Assis1, Maira Viana Rego Souza-Silva3, Polianna Delfino-Pereira3, Amanda Rabello Conceicao3, Anna Luiza Homan Araujo Carvalho1, Isabela Moraes Gomes3, Lucas Emanuel Ferreira Ramos3, Magda Carvalho Pires3, Milena Soriano Marcolino3 (1) Faculdade Ciencias Medicas de Minas Gerais (FCMMG); (2) Universidade Federal de Sao Joao Del-Rei (UFSJ); (3) Universidade Federal de Minas Gerais (UFMG) Introduction: There is a lack of studies investigating the influence of HIV infection, on the cardiovascular outcomes, in COVID-19 patients in Latin America. Objective: To compare cardiovascular outcomes, between patients with COVID-19 with and without HIV infection, in two consecutive years. Methods: This is a substudy of a multicentric cohort, which included 27 Brazilian hospitals, comprising March to September 2020 and March to December 2021. Cardiovascular outcomes included acute myocardial infarction (AMI), pulmonary thromboembolism (PTE), deep vein thrombosis (DVT) and stroke. Patients with COVID-19 and HIV coinfection were matched for age, sex, number of comorbidities and hospital. Groups were compared using the Chi-Square Test for categorical variables and the Wilcoxon test for continuous variables. Results were considered statistically significant at a significance level of p < 0.05. Results: From 17,101 COVID-19 patients, 130 were people living with HIV (PLHIV) (0.76%). Of these, 86 were hospitalized in 2020 and 44 in 2021. The median age in 2020 and 2021 periods was 53 and 54 years, respectively, with no significant differences between groups. The most frequent COVID-19 symptoms in both groups were dyspnea (2020: 52 [60.5%] vs 227 [67.0%]; p = 0.314/2021: 30 [68.2%] vs 122 [69.7%]; p = 0.989) and fever (2020: 50 [58.1%] vs 207 [61.1%]; p = 0.710/2021: 20 [45.5%] vs 76 [43.4%]; p = 0.942). The main cardiovascular outcomes between PLHIV in 2020 were PTE (4.7%), DVT (2.3%), AIM (2.3%), and stroke (1.2%). Non-HIV infected patients showed similar prevalence for the outcomes under study, with no significant difference. PTE (13.6%) and DVT (2.3%) were also the most common cardiovascular outcomes in PLHIV in 2021, however, no cases of AIM and stroke were observed in this group. Comparison of outcomes with the controls also showed no significant difference in this period. When observing the years of 2020 and 2021, there was a total reduction of cardiovascular outcomes, except for PTE. Conclusion: There were no significant differences in the cardiovascular outcomes between PLHIV and their controls. However, the reduction of the cardiovascular outcomes between 2020 and 2021 indicates the importance of vaccination in the prognosis of COVID-19 in HIV coinfected patients. 111913 Modality: E-Poster Scientific Initiation - Non-case Report Category: DIGITAL HEALTH/INNOVATION Diagnostic Accuracy of Smartwaches for Detection of Atrial Fibrilation: A Systematic Review LAIS ARAUJO CARNEIRO DE CAMPOS1, Lais Araujo Carneiro de Campos1, Marilia Menezes Gusmao1, Marilia Menezes Gusmao2, Julia Schoucair Neves1 (1) Escola Bahiana de Medicina e Saude Publica (EBMSP); (2) Escola Bahiana de Medicina e Saude Publica (EBMSP) Introduction: Atrial fibrillation is a common cardiac arrhythmia that affects about 59 million people worldwide. In many cases its diagnosis occurs late, due investigation of an ischemic stroke. In other situations, it presents a paroxysmal behavior, which makes it difficult to detect this arrhythmia in conventional electrocardiography exams. Among recent technologies being used to monitor and detect cardiac arrhythmias, the smartwatches are becoming very popular. For that reason, it is important to verify if those devices are accurate to detect atrial fibrillation. Objective: To describe the diagnostic accuracy of smartwatch-like devices in detecting atrial fibrillation. Methods: A systematic review was conducted using PRISMA methodology, between June and September 2021, in the Databases of Pubmed/Medline and Virtual Health Library. The descriptors used included the terms "watch", "wearable electronic devices", "photopletysmography" and "atrial fibrillation". After removal of duplicates, the results were screened for inclusion and exclusion criteria. Results: 409 articles were returned by the search, of which, 120 were duplicates. After screening the remaining 289 titles and abstracts for inclusion and exclusion criteria, 96 were selected for the second screening (full article read), of which 10 studies matched the criteria and were included in the review. The accuracy was measured on 10 different devices models produced by 5 companies. The sensitivity of the smartwatches included in the review varied between 67-100%, the specificity 67-99%, positive predictive value 80-90% and negative predictive value 85-100%. The accuracy was available in only two studies (70% and 97,5%). Conclusion: The smartwatches models reviewed by this study are accurate to detect atrial fibrillation. 111915 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hospitalizations for Cardiovascular Conditions Sensitive to Primary Health Care in Betim, Minas Gerais 2018-2020 FERNANDA AMPARO RIBEIRO1, SUELLEN MOURAO SILVA1, GILBERTO ANTONIO REIS1, GILBERTO ANTONIO REIS1, FERNANDA AMPARO RIBEIRO1, FERNANDA AMPARO RIBEIRO1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DE MINAS GERAIS - PUC-MG; (2) Fundacao de Amparo a Pesquisa do Estado de Minas Gerais - FAPEMIG Hospitalizations for Primary care-sensitive conditions are preventable health complications through disease prevention, diagnosis and care of acute conditions, monitoring of chronic conditions. The use of this indicator is based on the principle that effective and effective primary health care can prevent hospitalizations. Thus, a high number of Hospitalizations for primary care-sensitive conditions in a population points to difficulties in accessing and operating health services. Different activities of primary health care and specialized outpatient and hospital care were interrupted or paralyzed due to the priority given to COVID-19. For different reasons, both professionals and primary care users have dangerously delayed non-COVID-19 procedures, which could interfere with the effectiveness and effectiveness of primary health care and which, in turn, would reflect on Hospitalizations for primary care-sensitive conditions. Thus, the hypothesis presented is that the incidence of Hospitalizations for Primary care-sensitive conditions care in the population over 34 years of age in the city of Betim-MG may vary between the periods before and during the COVID-19 pandemic. Objective: To measure the occurrence of hospitalizations for cardiovascular conditions sensitive to primary care in adults over 34 years of age living in the city of Betim - Minas Gerais and to estimate the variability between the previous period and during the COVID-19 pandemic. Methods: This is an ecological, descriptive, longitudinal study with a quantitative approach. Data were extracted from the Hospital Information System available on the DATASUS, portal of the Ministry of Health. Descriptive statistical measures of data were used to analyze the variables included in the study. Results: Among hospitalizations for cardiovascular conditions sensitive to primary care in the period between 2018-2021 in the city of Betim-MG, it was observed that the total number of hospitalizations behaved in a stationary way year after year. At the same time, there was a drop in the number of emergency admissions in 2021 compared to 2018, 2019 and 2020. The population most affected by cardiovascular and cerebrovascular causes were black and brown people and men. Stroke was the main cause of elective and emergency admissions. 111919 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Epidemiological Profile of Live Births with Tetralogy of Fallot During the Period from 2016 to 2020 in Brazil LAURA COUTINHO VIANA1, Laura Coutinho Viana1, Jose Wilker Gomes de Castro Junior1, Marcello Vieira dos Santos1, Pedro Arthur Rodrigues de Oliveira1, Daniely Maues Beliqui1 (1) Centro Universitario do Estado do Para - Cesupa Introduction: Tetralogy of Fallot (TF) is a complex cyanotic congenital heart disease that involves changes in 4 cardiac segments in the newborn. They are: Right ventricular hypertrophy, aortic overriding of the interventricular septum, pulmonary artery stenosis, and sub-aortic interventricular communication (IVC). Its cause is multifactorial and affected pediatric patients may experience intense hypoxemic crises. Objective: This work aims to perform an evaluation of the epidemiological profile of live births with tetralogy of Fallot in Brazil in the period from 2016 to 2020. Methodology: A descriptive, retrospective and quantitative study was conducted based on secondary data provided by the Information System on Live Births (SINASC), SUS Department of Informatics (DATASUS). The collected information was stored and tabulated in Microsoft Office ExcelTM program. Results: Among the 527 cases found after analyzing the evaluated period, higher incidence is found in the years 2018, with 136 cases (25.8%) and 2019, with 126 cases (23.9%). The Brazilian region with the highest number of those born with TF was the Southeast region with 358 cases (67.9%) with the highest rate in the state of Sao Paulo with 286 cases (54.2%). Regarding racial profiles, whites were the highest number, with 310 cases (58.8%), followed by mixed race, with 158 cases (29.9%). Regarding gestational age, there were 369 cases (70.1%) of term pregnancy (37-41 weeks) and 134 cases (25.4) of premature pregnancy (before 37 weeks). Conclusion: Therefore, we observed a higher incidence profile of TF in children born in the state of Sao Paulo, white and born at term. The possible cause would be success in screening and identification of the disease, which is indifferent to early birth. 111942 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Chagas Disease: A Brazilian Epidemiological Overview BRUNO ENEAS ROLIM PAIVA1, Monique Benemerita Vilela Gomes1, Isabella Aparecida Abreu Garcia1, Isabela Rezende Costa1, Paulo Henrique Tenorio Queiroz1, Renata Adelia Alves de Oliveira1, Giovanna Maria Lopes Magalhaes1, Cleio Pereira dos Santos1, Paulo Jose da Silva1, Nisandra Pereira da Silva1, Ana Caroline Borges Lustosa1, Isabella de Almeida Nascimento1 (1) Universidade Federal do Piaui (Campus Senador Helvidio Nunes de Barros) Introduction: Chagas disease is a clinical condition caused by the protozoan Trypanosoma cruzi. This pathology is an important public health problem in Brazil, especially due to its cardiovascular complications. In average, between 10 and 30 years after the acute infection, 30% of the infected have chronic Chagas disease cardiomyopathy, which is the main cause of morbidity in this pathology, and sudden death is the main cause of mortality in those cases. Goals: To assemble an epidemiological overview of Chagas disease in Brazil. Methods: For this analysis, an epidemiological study was made using the data about acute Chagas disease in the Notifiable Diseases Information System (SINAN/DataSUS). The search considered the data from 2016 to 2020, grouping the number of confirmed cases by region of notification and sex. Hereafter, a data search of the number of deaths due to acute Chagas disease was performed using the same filters. Moreover, this study determined the Brazillian population by using the demographic census of 2010 from the Brazilian Institute of Geography and Statistic (IBGE). Results: According to DataSUS, between 2016 and 2020, there were 1662 notified cases of Chagas disease, affecting mostly and being more deadly in males. Between 2017 and 2019, an increase of 12.94% occurred, and 2019 was the year with most notifications, representing 23.1% of the cases between 2016 and 2020. The North region showed relatively more cases, representing 91.66% of deaths and 94.64% of the notified cases, with approximately 0.012% of the population being infected. Conclusion: The majority of the cases of Chagas disease occurs in the North region, therefore, the most cases of Chagas disease cardiomyopathy. Furthermore, it was observed that many regions do not notify new cases of Chagas disease, making it harder to paint a real epidemiological estimative and intervention necessity throughout the country. Besides that, in 2020 there was a decrease in notifications, explained by the Covid-19 pandemic, that caused a reduction in the notification of diseases non-related to respiratory syndromes. 111949 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY The Decrease of Heart Transplantation During the COVID-19 Pandemic in Brazilian Reality: A Comparative Study between Socio-Demographic Regions LARISSA DE OLIVEIRA BELTRAO1, Beatriz Ximenes Bandeira de Morais1, Maria Leticia Garrote Bulhoes2, Andreza Leite Marques de Sa Souza1, Luiza Dias Aguiar1, Leticia Ferreira Leal3, Isabela Torres Castro1, Juliana Mirelly Moura de Oliveira1, Catiane Kelly Schaefer4 (1) Faculdade Pernambucana de Saude (FPS); (2) Universidade Estacio de Sa (UNESA); (3) Universidade de Pernambuco (UPE); (4) Universidade de Santa Cruz do Sul (UNISC) Background: Heart transplantation is the therapeutic option for refractory heart failure cases and is a procedure with limited access in many underdeveloped countries. With the COVID-19 pandemic, health resources were directed to contention plans and patient management, leading to a global decrease in transplantations. Objectives: This study aims to demonstrate the disparity in the impact of the COVID-19 pandemic on heart transplantation among the sociodemographic regions of Brazil. Methods: This is a retrospective descriptive study with data from the Department of Informatics of the Unified Health System from 2018 to 2021. A comparative analysis was performed between the average of the first two years of study and the two subsequent years, before and during the pandemic, respectively. Results: Between 2018 and 2021, 1,146 Brazilians underwent heart transplantation. Before the COVID-19 pandemic, 159.5 transplants were achieved in the Southeast region, the most developed in Brazil, 53.5 in the South, 31.5 in Midwest, and 80 transplants in the Northeast. With the COVID-19 pandemic, there was a drop to 41 procedures executed in the Northeast, 24.5 in the Midwest, 25.5 in the South, and 157.5 in the Southeast. Conclusion: There was a decrease of approximately 50% of heart transplants achieved in the Northeast and South, while there was maintenance in the numbers of other regions, which are two of the three most developed regions of Brazil. 111953 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Central Pressure, Arterial Stiffness and Sympathovagal Balance After SARS-COV-2 Infection: Difference between Sexes ANA LUIZA DE ARAUJO GARCIA1, Ana Luiza de Araujo Garcia1, Maria Luiza Rangel de Vasconcellos Guerra1, Michelle Rabello da Cunha1, Samanta de Souza Mattos1, Mario Fritsch Toros Neves1 (1) Universidade do Estado do Rio de Janeiro (UERJ) Introduction: Acute infection caused by the SARS-CoV-2 can generate functional changes in the vascular endothelium but structural vascular alterations and long-term effects on the sympathovagal balance are still unknown. Objective: To compare central hemodynamic parameters, arterial stiffness, and autonomic activity between men and women with a history of symptomatic COVID-19. Materials and Methods: Cross-sectional study with patients aged between 30 and 70 years, both sexes, submitted to clinical evaluation, central hemodynamic parameters and pulse wave velocity (PWV) by Mobil-O-Graph, and sympathetic tone by heart rate variability (HRV). Patients were divided into two groups: Control (n = 25) with patients with no history of COVID-19, and post symptomatic COVID (n = 29), which included patients with positive RT-PCR in the last 12 months before enrollment in the study. An intragroup analysis was performed to verify the differences between men and women. Results: Patients were predominantly female in both groups (64 vs 62%, p = 0.883) and with similar ages (55 +- 6 vs 51 +- 10 years, p = 0.088). In the analysis by sex, the frequency of hypertension was similar between men and women in the control group (100 vs 81%, p = 0.243) and in the post-COVID group (60 vs 56%, p = 0.570). The post-COVID group presented, in females, higher peripheral systolic and diastolic pressures (114 +- 15 vs 131 +- 23 mmHg, p = 0.040; 72 +- 9 vs 85 +- 16 mmHg, p = 0.013), central systolic pressure (106 +- 15 vs 122 +- 23 mmHg, p = 0.037), augmentation pressure (5 +- 3 vs 11 +- 7 mmHg, p = 0.018), augmentation index (16 +- 7 vs 30 +- 12%, p = 0.006) and pulse wave velocity (6.7 +- 0.9 vs 7.8 +- 1.6 m/s, p = 0.033). The control group showed no significant difference between sexes in these parameters. HRV indices were similar for both sexes in both groups. The sympathovagal balance, represented by the low frequency/high frequency (LF/HF) ratio, was higher in men in the post-COVID group (4.7 +- 8.6 vs 1.2 +- 1.5, p = 0.185), although not reaching statistical significance. Conclusion: Early vascular aging, characterized by higher arterial stiffness and increased central pressure, was more evident in women who had symptomatic COVID-19 compared with men in the same group, even without differences in sympathovagal balance. 111963 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR PHARMACOLOGY The Effectiveness of Beta-Blockers in the Treatment of Hypertensive Patients ISRAEL FIGUEIRA LEMOS1, Alice Jacomini Barcos1, Gabriel do Nascimento Oliveira1, Ana Lucy Peixoto Rabelo1, Camila Namie Seki Garzon1, Edson Luis de Barros Siqueira1, Ana Luiza Nepomuceno Sampaio1, Caroline Hipolito Pires1, Luma Maria Favacho Bordalo1, Maria Eduarda Dantas da Veiga1, Juliana de Sousa Tavares1, Erick Clayton Goncalves Feio1 (1) Universidade do Estado do Para Introduction: Beta-blocker drugs are widely used in the treatment of systemic arterial hypertension, being able to be used in monotherapy treatments or combined with other medications. However, due to their complex pharmacological actions and adverse effects, the effectiveness of beta-blockers raises uncertainties. Objectives: Evaluate the effectiveness of beta-blockers in the control of hypertension. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, using the PICO strategy to elaborate the guiding question "Have beta-blockers been effective in hypertensive people?". The data collection was based on the use of the following keywords: "beta blockers'' AND "effectiveness" AND "systemic arterial hypertension", which were obtained in English and Portuguese on the Medical Subject Headings (DeCS/MeSH). The articles were searched on the PubMed and Biblioteca Virtual em Saude (BVS) databases, including those that approach the treatment of beta-blockers in systemic arterial hypertension, indexed in the selected databases and published between 2012 and 2022, in Portuguese and English. All studies that are not randomized clinical trials were excluded. Results: A total of 20 articles were selected to integrate this study. Traditional beta-blockers (BB) are efficient agents to reduce BP, but they're not recommended as standard therapy to uncomplicated essential hypertension, for being less efficient in reducing cardiac events. However, new generation BB's, nebivolol for example, has auxiliary vasodilating properties. Compared to ACE inhibitor therapy, BB therapy was superior in hypertensive patients and required fewer antihypertensives to control BP. Furthermore, BB effects had different outcomes in regard to age, sex, ethnicity and daily habits. Conclusion: In general lines, a positive response was seen on the hypertensives' treatment with beta-blockers, considering the singular effects of the medicine's actions of vasodilation and complacency on hypertensive patients, according to the drug manipulation, different treatments and varied physiologies. 111971 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Decompensated HF in the Extreme Elderly: Characteristics and Outcomes. Data from a Hospital Record LARISSA MELO TARGINO1, Claudio Lucas Silva Cunha1, Larissa Melo Targino1, Helen de Araujo Alves2, Luiz Eduardo Fonteles Ritt2 (1) Escola Bahiana de Medicina e Saude Publica (EBMSP); (2) Hospital Cardio Pulmonar da Bahia (HCP) Introduction: The trend towards population aging and its direct association with the prevalence of heart disease has resulted in a higher incidence of Heart Failure (HF). However, extreme old patients are still underrepresented in clinical studies and few data regarding their profile and prognosis is present in the literature. Objective: To describe and compare clinical characteristics and clinical outcomes between extreme elderly (>=80 years-of-age) and their counterparts patients hospitalized for decompensated HF. Methods: Prospective cohort study in a single-center registry model. Patients hospitalized for HF at a private institution in Salvador, Bahia, Brazil, were included. Data were obtained from hospital records from 2019 to 2022. In addition, telephone follow-up was carried out 30 days after discharge, when the outcomes of death or readmission were measured. A p < 0.05 was set as a level of significance for all analyses. Results: We analyzed 356 patients hospitalized for HF, who were divided into groups of extreme elderly (n = 159) and non-extremely elderly (n = 197). Compared to the non-extremely elderly group, the extreme elderly group were more likely to be female, had hypertension and was less likely to have obesity, smoking, use of a pacemaker, had paroxysmal nocturnal dyspnea and third beat extra heart sounds. The group >=80 years had higher values of Left Ventricular Ejection Fraction (mean = 48.56, 95% CI [46.16-50.96] versus mean = 41.43, 95% CI [38.9-43.9]; p < 0.001), as well as higher levels of urea and brain natriuretic peptide (BNP) at discharge. There was no difference in the rate of betablocker or ACE inhibitor/angiotensin receptor blocker usage between groups. During hospitalization and the 30-day follow-up, the mortality in the extreme elderly group was significantly higher (28.9% versus 14.4%; p = 0.047). Within 30 days after discharge, 7.9% of patients <80 years were readmitted, while 13.4% of patients >=80 years-of-age, although without statistical significance. Conclusion: Extremely elderly patients with HF are susceptible to higher mortality rates and have a particular clinical profile. Future studies focusing on the treatment of these subgroup are warranted. 111974 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Clinical and Epidemiological Profile of Patients with Stemi Treated at a Referral Hospital KARLA SANTOS PINTO1, Beatriz Barbosa Viana1, Larissa Xavier Gomes da Silva1, Joao Pedro Martins Moreira Granja1, Elias Soares Roseira1, Taina Viana1, Luiz Carlos Passos1, Pollianna Roriz1, Adriano Tamazato1, Raissa Barreto Lima1, Ana Luisa de Aguiar Almeida Silva1, Eduarda Luciana Mendes Borges1 (1) Hospital Ana Nery Introduction: Coronary Artery Diseases (CAD) are responsible for the highest mortality rate in the world. Acute ST-segment elevation myocardial infarction (STEMI) corresponds to one third of CAD and has a higher mortality among the disease subtypes. Early diagnosis and prompt reperfusion are effective ways to limit ischemia, reducing the risk of complications. Angioplasty is the main reperfusion strategy and, if it is not performed within 120 minutes, fibrinolysis therapy must be managed. Objective: To describe the epidemiological and therapeutic clinical profile and clinical consequences in a tertiary referral hospital in the city of Salvador - BA, which receives an average of 50 patients per month in this condition. Methodology: Descriptive study with 329 patients treated at health units in Salvador and the metropolitan region with suspected AMI, transferred through the AMI Protocol - SAMU for angioplasty proposal in a referral hospital, between January 2021 and April 2022. demographic variables, risk factors, first care, angiographic data, and outcomes. Categorical variables were presented as frequencies and continuous variables as mean or median. Results and Discussion: There were 329 patients with STEMI, 60% of whom were men. The mean age was 61 years. Previous diseases were SAH (64%), DM (32%) and obesity (15%). 19% were smokers and 16% were ex-smokers. Most with Killip I in the first evaluation (84.8%). The most affected wall was the anterior one (46%). The most performed reperfusion was primary angioplasty (71.4%). The average time for the balloon holder was 354 minutes. The most frequent culprit artery was the anterior descending artery (47.1%), followed by the right coronary artery (28.2%). There was occlusion in 43.4% and none in 12% of the cases. Most access was via the Radial artery (76%). 40% had an initial TIMI of 0 and 20% had a TIMI of 3. 65% of the patients had a final TIMI of 3 and only 4.3% had a final TIMI of 0. Angioplasty was successful in about 70% of cases. As an outcome, there was death of 6, 6% during hospitalization. Conclusion: Patients undergoing primary angioplasty were men with anterior wall AMI. Despite the long door-to-balloon time, a high success rate was obtained in restoring normal flow after the procedure. These results corroborate the generation of strategies to reduce injuries in patients undergoing angioplasty. 111985 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Hospitalizations for Cardiovascular Conditions Sensitive to Primary Health Care in Betim, Minas Gerais 2018-2021 FERNANDA AMPARO RIBEIRO1, FERNANDA AMPARO RIBEIRO1, SUELLEN MOURAO SILVA1, GILBERTO ANTONIO REIS1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DE MINAS GERAIS - PUC-MG; (2) Fundacao de Amparo a Pesquisa do Estado de Minas Gerais - FAPEMIG Hospitalizations for Primary care-sensitive conditions are preventable health complications through disease prevention, diagnosis and care of acute conditions, monitoring of chronic conditions. The use of this indicator is based on the principle that effective and effective primary health care can prevent hospitalizations. Different activities of primary health care and specialized outpatient and hospital care were interrupted or paralyzed due to the priority given to COVID-19. For different reasons, both professionals and primary care users have dangerously delayed non-COVID-19 procedures, which could interfere with the effectiveness and effectiveness of primary health care and which, in turn, would reflect on Hospitalizations for cardiovascular conditions sensitive to primary care. Patients with cardiovascular diseases are more vulnerable to hospitalizations due to adverse events related to poor symptom control. Thus, the hypothesis presented is that the incidence of Hospitalizations for cardiovascular conditions sensitive to primary care in the population over 34 years of age in the city of Betim-MG may vary between the periods before and during the COVID-19 pandemic. Objective: To measure the occurrence of hospitalizations for cardiovascular conditions sensitive to primary care in adults over 34 years of age living in the city of Betim - Minas Gerais and to estimate the variability between the previous period and during the COVID-19 pandemic. Methods: This is an ecological, descriptive, study with a quantitative approach. Data were extracted from the Hospital Information System available on the DATASUS, portal of the Ministry of Health. Descriptive statistical measures of data were used to analyze the variables included in the study. Results: Among hospitalizations for cardiovascular conditions sensitive to primary care in the period between 2018-2021 in the city of Betim-MG, it was observed that the total number of hospitalizations behaved in a stationary way year after year. At the same time, there was a drop in the number of emergency admissions in 2021 compared to 2018, 2019 and 2020. The population most affected by cardiovascular and cerebrovascular causes were black and brown people and men. Stroke was the main cause of elective and emergency admissions. The COVID-19 pandemic had an important impact on the care routine of all health service users. It is necessary to carefully investigate the long-term impacts of this health crisis. 111986 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Predictors of Heart Failure with Improved Ejection Fraction on Patients with Chagas Disease GABRIELLY NASCIMENTO1, Celina Maria de Carvalho Guimaraes1, Silvia Marinho Martins1, Luis Eduardo Martins Alves1, Taciane Queiroz Medeiros Gomes1, Maria Elisa Lucena Sales de Melo1, Maria da Gloria Aureliano de Melo1, Carolina de Araujo Medeiros1, Maria das Neves Dantas da Silveira Barros1, Maria da Piedade Costa Reis de Albuquerque1, Cristina de Fatima Velloso Carrazzone1, Wilson Alves de Oliveira Junior1 (1) Pronto Socorro Cardiologico de Pernambuco - PROCAPE Introduction: Heart failure with improved ejection fraction (HFimpEF) is associated with improved clinical outcomes , however little is known about HFimpEF of chagasic etiology . Objective: Identify predictors of progression to HFimpEF in Chagas' etiology. Methodology: Cohort study in a referral outpatient clinic for Chagas Disease admitted between march-2016 and august-2019. From the 862 included in database, 86 were selected, under two criteria from two different echocardiograms (echos), the first was the admission one, with left ventricular ejection fraction (LVEF) <40%, and the second one, the follow-up. The mean time interval between the echos was 3.13 years (1 +- 5 years). HFimpEF was defined as LVEF >=40% on the follow-up echo. The variables analyzed were sex, age, presence of comorbities (diabetes mellitus, dyslipidemia and arterial hypertension), medications: spironolactone, beta-blockers, loop and thiazide diuretics, angiotensin II receptor blocker/angiotensin converting enzyme inhibitor and sacubitril valsartan, left ventricle end-diastolic diameter (LVEDD) and right ventricule function to the Echo, QRS duration, presence of right bundle branch block and left bundle branch block on the electrocardiogram. For data analysis the technique utilized was a logistic regression with variables that presented p-value < 0,15 in the univariate analyses. Results: On admission, mean age was 60.9 years (standard deviation 11.5, minimum 30 and maximum 80), 52% women, 77.7% had arterial hypertension, 19.7%: diabetes, 33.7%: dyslipidemia. On the electrocardiogram: 43% right bundle branch block, 37.2% left bundle branch block. On the admission echo, LVEF with median 33% (minimum 16%, maximum 39%), LVEDD average of 65(standard deviation: 1,25, minimum 45, maximum 81) and 25.5% with right ventricle dysfunction. On therapeutics: 95.3% beta blockers, 77.9% used loop and thiazide diuretics, 74.4% angiotensin II receptor blocker/angiotensin converting enzyme inhibitor, 67.4% spironolactone, 8.1% sacubitril valsartan. In the univariate analysis, use of spironolactone (p = 0.027) and LVEDD (p = 0.001) were shown to be factors for improving LVEF, but in the multivariate analysis, only LVEDD (Odds Ratio 0.87, 95% CI 0.80-0.95, P = 0.002) was an independent predictor associated with improvement in LVEF. Conclusion: In agreement with the literature when analyzing different etiologies, in Chagas' etiology, only LVEDD was able to predict progression to HFimpEF. 111990 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Acute Rheumatic Fever: An Epidemiological Analysis of Hospitalizations in the Northern Region of Brazil between 2017 and 2021 GIULIA VITORIA NASCIMENTO DA SILVA1, IGOR LUCAS FARIAS LIMA1, MARCOS AURELIO VIEIRA DA COSTA FILHO2, JULIA DE MOURA CARVALHO FARIA1, WANDA MARIA DE FRANCA PIRES2, ARIANE LOBATO MORAES2, LARISSA DACIER LOBATO COMESANHA2, LUCIANO MOURA DE ASSUNCAO3 (1) Universidade do Estado do Para (UEPA); (2) Universidade Federal do Para (UFPA); (3) Fundacao Santa Casa de Misericordia do Para Introduction: Rheumatic fever (RF) is a pathology that follows as an immune response to an infection from group A b-hemolytic Streptococcus. Its prevalence is higher in sub-evolved countries, being that around 15 million cases in the world are linked to valve damage, a characteristic of chronic rheumatic heart disease - most serious manifestation of the disease. Objective: To analyze the epidemiological profile of hospital admissions, mortality and cost per hospitalization resulting from acute RF with cardiac in the northern region of Brazil, from 2017 to 2021. Methods: Observational, cross-sectional, analytical-descriptive and quantitative study based on data from Sistema de Informacoes Hospitalares do SUS (SIH/SUS) - DATASUS. The number of hospitalizations, age, sex, average hospital stay, average cost per hospitalization and mortality rate were analyzed, referring to hospitalizations due to acute RF in the North region of Brazil, from 2017 to 2021. Results: In the period described, 868 hospitalizations for acute RF were reported in the Northern region of Brazil. The lowest number occurred in 2021, with 99 admissions and the highest in 2018 and 2019, with 219 and 218 cases, respectively. The average number of hospitalizations per year was 173.6. Females represented 53.6% (465) of the hospitalizations and males 46.4% (405). The most affected age groups were 5 to 14 years old, with 263 (30.2%), and 40-49 years old, with 101 cases (11.6%) of the total. Children under 5 years had 44 admissions and adults over 20 years old had 515 cases. The average length of hospitalizations during 2017 and 2021 was 6.1 days and the standard deviation was 0.67 between the annual values. The shortest admission time was in 2018, with an average of 5.2 days, and the longest was in 2020 with 7.2 days. The mortality rate was 1.14% with the lowest in 2019 (0.46%) and the highest in 2021 (3.03%). R$328,658.56 was spent on hospitalizations with an average cost of R$373.04. Conclusion: The number of hospitalizations gradually decreased during the study period. Among these hospitalizations, most were women and the main age group affected was children between 5 to 14 years old. The mortality rate followed a pattern contrary to the hospitalization rate, increasing gradually until 2021. It is notorious for the necessity of affirmative actions in public health to prevent the disease and reduce its impact on the brazilian health and economic system. 111996 Modality: E-Poster Scientific Initiation - Non-case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS The Influence of Educational Level on the Suspicion of Acute Myocardial Infarction (AMI) in Patients of the Public Health System of Salvador - BA JULIA SCHOUCAIR NEVES1, Pollianna de Souza Roriz1, Fabiana Benevides Pontes1, Mariana Mendonca de Almeida1, Frederico Gesteira de Viveiros Junior1, Joao Gabriel Batista Simon Viana1, Franciele Mascarenhas Alves Luz1, Marianne Soglia Calixto Costa1, Luiz Ricardo Cerqueira Freitas Junior1, Victoria Kelly Lima de Castilho1 (1) Servico de Atendimento Movel de Urgencia - SAMU Introduction: Social determinants of health -such as the level of one's education - as risk factors for cardiovascular diseases have been highlightened by several studies. These determinants are directly related to the prognosis, and may impact the patient's identification of the disease itself. In this context, the present study aims to evaluate the influence of the level of education on the self-perception of disease in patients with ST-segment elevation Acute Myocardial Infarction (STEMI) treated in the public health system of the city of Salvador - BA. Methods: A cross-sectional study, carried out with data collected from the STEMI survey from Salvador (PERSISST), which analyzed the association between suspected AMI in patients who had a heart attack between January/2019 and December/2021 and their corresponding level of education. The sample of 859 people was divided into Group I - patients who did not suspect AMI - and Group II - patients who suspected AMI -. Each group was subdivided into 5 different levels of education. Such division of groups aimed to possibly identify an association between the lowest level of education with a lower suspicion of the condition in question. Results: 859 patients were included in the survey (590 in Group I and 269 in Group II). In both groups there was a predominance of male patients, with no difference between the two groups in terms of gender and age. In Group I, 26.8% (158) had gone to school until the 4th year of elementary school; 27.1% (160) had finished elementary school (up to 5th grade); 18.6% (110) had finished middle school (up to 9th grade); 21.2% (125) finished high school and 6.3% (37) had graduated from college. While in Group II, the following distribution was observed in terms of education: 23.8% (64) up to 4th grade; 20.4% (51) finished elementary school, 18.2% (49) finished middle school; 27,9% (75) finished high school and 9.7% (26) finished college. After comparing the groups, it was found that patients with a lower level of education had a lower degree of suspicion, pointing to a statistically significant difference of p = 0.034. Conclusion: In our sample, composed by STEMI patients treated by the public health system of Salvador, the low level of education was related to the patient's lower self-suspicion of heart attack. This analysis reinforces the need for educational measures, which could positively influence the early recognition of time-dependent diseases. 112013 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Epidemiological Profile of Patients Affected by Chagas Disease in the State of Para between 2010 a 2020 ARIANE LOBATO MORAES1, Ariane Lobato Moraes1, Icaro Jose Araujo de Souza1, Cassio Kenzo Camara Yamada2, Jayssa Leite Freitas3, Bruna Araujo Smith3, Giovana Fonseca Pontes3, Rayane Calandrini de Azevedo3, Luciano Moura de Assuncao4 (1) Universidade Federal do Para (UFPA); (2) Universidade do Estado do Para (UEPA); (3) Centro Universitario do Para (CESUPA); (4) Fundacao Santa Casa de Misericordia do Para (FSCMPA) Introduction: Chagas disease or American trypanosomiasis is a parasitic infection caused by the protozoan Trypanosoma cruzi. Transmission occurs from the contact of the injured skin or mucous membranes with contaminated feces, mainly through the ingestion of contaminated food, such as acai. Affected individuals may develop Chagas myocarditis, with possible electrocardiographic changes. Objectives: To analyze the epidemiology of Chagas disease cases in the state of Para, from 2010 to 2020, analyzing the following variables: sex, race, age group, area of residence, probable mode of infection and disease evolution. Methods: This is an epidemiological, descriptive and analytical study, whose data were collected in the Notifiable Diseases Information System (SINAN) made available by the Department of Informatics of the Unified Health System (DATASUS), referring to reported cases of Acute Chagas, in the state of Para, from 2010 to 2020, totaling 2,221 cases. For the statistical analysis, the Chi-Square test of equal expected proportions was used, through the Bioestat 5.3 program, in order to calculate the p-value of the data found. Data with p value < 0.05 were considered significant. There was no need for submission to the research ethics committee. Results: This study showed that, of the 2.221 reported cases, there was a higher frequency of Acute Chagas Disease in brown patients (80.10%), male (55.16%) and in adults between 20 and 59 years old (58, 89%). The most frequent route of transmission was oral (79.78%). The significant number of unreported data prevents a more detailed analysis. Finally, the predominant evolution was the survival of 86% of the total cases in the analyzed period. Conclusion: The study reports that the epidemiological profile of the patient with Chagas cardiomyopathy between the years 2010 to 2020 is a male patient, brown and aged between 20 and 59 years. In addition, underreporting and missing data are relevant features. Thus, we identified the demand for new studies in order to generate more data and promote public policies aimed at reducing the incidence of Chagas Disease in the region. 112017 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Alcohol Consumption and Atrial Fibrillation Incidence in Brazilian Capitals: A Population-Level Study ROBERTA GABRIELA DA SILVA1, Lais Vitoria de Andrade Miranda1, Roberto Vieira Botelho4, Rodrigo Alves da Silva4, Marcelo Vieira Damiao5, Marcio Sommer Bittencourt3, Miguel Morita Fernandes da Silva2, Odilson Marcos Silvestre1 (1) Universidade Federal do Acre; (2) Universidade Federal do Parana; (3) University of Pittsburgh; (4) Instituto do Coracao do Triangulo; (5) ITMS Telemedicina Brasil Introduction: Alcohol consumption can lead to tachyarrhythmias, particularly atrial fibrillation. Aim: We evaluated the association between alcohol consumption at the population level and the incidence of atrial fibrillation/flutter (AF) in Brazilian capitals. Methods: We performed an ecological time-series study using electrocardiogram (EKG) reports in all Brazilian capitals from 2008 to 2013. EKG data were provided by ITMS Telemedicine Network, and the diagnosis of AF was defined according to the EKG medical report. Abusive alcohol consumption at each capital, defined as the estimated proportion of individuals who binge drinking (>=4 doses for women and >=5 doses for men, on an occasion), was estimated from the Surveillance of Risk and Protective Factors for Chronic Diseases by Telephone Survey (VIGITEL) in the respective year and divided in terciles: 1st tercile (10.6-14.6%); 2nd tercile (14.7-16.9%); 3rd tercile (17.1-26.6%). A stratified two-stage weighted survey analysis was performed to estimate the incidence of AF at each tercile of alcohol consumption. Results: We evaluated 474,357 EKGs (48.8 +- 18.5 years old, 50% women) performed in all 27 Brazilian capitals. The incidence of AF was significantly higher in the 3rd tercile (5.3%, 95% Confidence interval [CI] 1.6, 9.0%) as compared with the 2nd (1.5%, 95%CI 1.2, 1.7%) and 1st (2.1%, 95%CI 1.7, 2.6%, p < 0.001, figure) terciles of alcohol consumption, respectively. Conclusion: In this population-level study of Brazilian capitals, higher alcohol consumption was associated with increased incidence of AF. 112027 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Prevalence of Electrocardiographic Abnormalities Detected by a Telediagnosis Service in Primary Care in a Municipality in Southern Brazil HENRIQUE GUIMARAES AIRES E SILVA1, Pedro Ermel Martins1, Marcia Barbosa de Freitas2, Chaiana Esmeraldino Mendes Marcon1 (1) Universidade do Sul de Santa Catarina; (2) Instituto Nacional de Cardiologia Background: The 12-lead electrocardiogram (ECG) is one of the most used tests in the evaluation of cardiovascular diseases (CVD) in primary health care (PHC) because it is cheap and available in the Sistema Unico de Saude (Brazil's health care model). However, particularities in the frequency of electrocardiographic findings are observed when population characteristics are considered. Objective: To identify the main electrocardiographic abnormalities and the clinical and epidemiological factors associated with their occurrence in primary health care. Methods: This study analyzed all ECG and application forms of patients submitted to primary care examination over 20 years of age in a municipality of Santa Catarina - Brazil - in 2020. Descriptive analysis of the data and statistical inference was performed. The level of significance adopted was 5%. Results: ECGs of 1907 patients were analyzed, 57.37% of them abnormal. The mean age of the patients was 54,8 +- 15,0 years-old. The abnormalities found varied according to age group, however the most common were nonspecific changes in ventricular repolarization (52.93%), right branch conduction block (28.52%), left ventricular overload (12.07%), electrically inactive areas (10.42%) and divisional blocks of the left branch (8.96%). The main clinical and epidemiological factors related to the presence of an abnormal ECG were age over 60 years (OR 2.17 [CI 95% 1,79-2,62]), systemic arterial hypertension (OR 1.76 [CI 95% 1,46-2,11]), diabetes mellitus (OR 1.78 [CI 95% 1,38-2,30]), dyslipidemia (OR 1.87 [CI 95% 1,49-2,34]), previous acute myocardial infarction (OR 5.63 [CI 95% 1,28-24,72]), previous myocardial revascularization surgery (OR 8.24 [CI 95% 1,06-64,01]), or the use of any medication (OR 1.55 [CI 95% 1,27-1,88]). The report of the electrocardiogram by the cardiologist was made available with less than two days in more than 70% of the tests. Conclusion: The evaluation of the prevalence of electrocardiographic findings and associated factors allows the construction of pre-test probability, which is essential in the context of public health for the indication of the examination rationally and without burdening Brazil's health care system. The use of telediagnostic resources in this setting allowed to minimize the effects of the large geographic dimentions and social disparitys that exist in Brazil. 112030 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Cardiotoxicity by Anthracyclines in Cancer Treatment: Systematic Review DAVI GABRIEL BARBOSA1, Paola Bitar de Mesquita Abinader2, Ana Paula Correa de Lima2, Ana Claudia Reis Guilhon2, Camila Rodrigues Maciel2, Fernando Gabriel Rodrigues Pereira1, Isabella Soares Souza3, Luiz Fernando Leite da Silva Neto1, Fernando Tavares Brasil Teixeira1, Luis Eduardo Werneck de Carvalho4 (1) Universidade do Estado do Para - UEPA; (2) Centro Universitario do Para - CESUPA; (3) Universidade Federal do Para - UFPA; (4) Sociedade Brasileira de Cancerologia - SBC Introduction: Immunotherapies have demonstrated a relevant effect on the prognosis of neoplasms over the years. However, antineoplastic agents increase the risk of cardiovascular disease by inducing cardiotoxicity. Objective: To analyze the induction of cardiovascular diseases by cardiotoxicity caused by antineoplastic drugs in cancer patients. Methods: Systematic review about cardiotoxicity due to antineoplastic treatment, whose data were obtained through the Biblioteca Virtual da Saude (BVS) from the last 5 years, using the PICO with PRISMA strategy, excluding case reports. The descriptors used were antineoplastic, cardiotoxicity, and anthracycline. Results: On the clinical aspects, no deaths were reported due to cardiotoxicity, i.e., anthracyclines did not cause any effect on mortality, and cardiotoxicity with the occurrence of heart failure was not statistically significant in treatment with anthracyclines. But 4 studies have analyzed the occurrence of arrhythmias, presenting statistically significant numbers, occurring in 317 patients. 3 studies have addressed the side effects of cardioprotective drugs: hypotension, acute pulmonary edema (enalapril), and bradycardia (metropol). About cardiac markers the changes in CK-MB, Troponin I and NT-proBNP were statistically significant along with markers of inflammation and oxidative stress having increased IL-6 and ROS1 with anthracycline treatment. On LVEF The cardioprotective drugs showed a statistically significant benefit in preventing LVEF reduction compared to the control group (MD 3.57, 95% CI 93%). Also, analyzing the cardioprotective drugs, a positive trend was found with the studies involving beta-blockers. The SRAA blockers as a cardioprotective drug also had positive results regarding LVEF. The cardioprotective effects were positive and similar in the various types of chemotherapeutic drugs: doxorubicin and epirubicin, especially in a study addressing breast cancer patients where LVEF obtained a considerabldifference, The cardioprotective drugs showed a possible benefit in preventing the reduction of Mitral Peak E/A Wave Velocity. Conclusion: In summary, there was an increase in inflammatory and cardiac markers and the presence of cardiotoxicity with the occurrence of arrhythmias by the use of anthracyclines. Moreover, the use of drugs with cardioprotective potential has efficacy in preventing the reduction of left ventricular ejection fraction, such as angiotensin-converting enzyme inhibitors. 112031 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Medical Therapy Optimization During Hospitalization for Acute Heart Failure Relates to Better Prognosis RAFAEL MORETTI1, Michelle Bozko Collini1, Karoline Cordeiro Vercka1, Carolina Ruschel Senger1, Jorge Tadashi Daikubara Neto1, Matheus Bissa Duarte Ferreira1, Jessica Tamires Reichert1, Lucas Muller Prado1, Gustavo Sarot Pereira da Cunha1, Leonardo Henrique dos Santos Melo1, Jose Renan de Matos Pain1, Miguel Morita Fernandes da Silva1 (1) Complexo Hospital de Clinicas da Universidade Federal do Parana (CHC-UFPR) Background: Initiating or uptitrating doses of modifying-disease drugs for heart failure (HF) is recommended during hospitalization for decompensated HF. However, data on the impact of HF medical therapy optimization (MTO) during hospitalization on long-term prognosis is scarce. Objectives: This study aims to evaluate the association of MTO during hospitalization and the composite outcome of re-hospitalization and death in patients with decompensated HF. Methods: Prospective cohort study that included patients >18 years old admitted for decompensated HF in a tertiary hospital from October 2019 to February 2022. Patients with ejection fraction >50% or who died during hospitalization were excluded. MTO was defined as any of the following during hospitalization: 1) addition of one of the following classes: ACE-I (Angiotensin-Converting Enzyme Inhibitors)/ARB (Angiotensin II Receptor Blockers)/ARNI (Angiotensin Receptor-Neprilysin Inhibitor), beta-blocker, spironolactone and SGLT2 inhibitor; 2) exchange of ACE-I/ARB for ARNI; or 3) reaching the target dose of one of these medications already in use. The outcome was the composite of re-hospitalization or death from any cause during a follow-up of up to 180 days. Survival analysis was performed by COX regression adjusted for confounding factors. Results: 109 patients were analyzed (66 +- 14 years old, 40% women, ejection fraction: 33 +- 9%), with 36 (33%) presenting the composite outcome. Compared to patients without MTO (n = 44), those with MTO (n = 65) had lower serum creatinine values [1.1 (0.8-1.5) vs 1.4 (0.9-2.0) mg/Dl; p = 0.014) and higher systolic blood pressure [129.7 +- 23.9 vs 119.8 +- 22.8 mmHg; p = 0.035] at hospital admission, and were less likely to have decompensated due to infectious causes (7.7% vs 20.5%; p = 0.05) or non-adherence to sodium and water restriction (1.5% vs. 18.2%, p = 0.002), respectively. After adjusting for these confounders, therapeutic optimization was associated with a lower incidence of the composite outcome (Hazard Ratio: 0.42; 95% Confidence Interval: 0.18-0.96, p = 0.039). Conclusion: In patients with decompensated HF, therapeutic optimization during hospitalization was associated with a lower incidence of the composite outcome of death or re-hospitalization in the 6-month follow-up. 112040 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Correlation between Distance Covered in the Stress Test and B-Lines Detected on Lung Ultrasound in Outpatients with Heart Failure with Reduced Ejection Fraction ALICE ZANETTI DUSSIN1, Anna Paula Tscheika2, Luiz Claudio Danzmann3, Marcus Vinicius Simoes4, Andrielle Dias Pinheiro2, Luiz Carlos Bodanese1 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS); (2) Hospital Sao Lucas da PUCRS (HSL); (3) Universidade Luterana do Brasil (ULBRA); (4) Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP) Background: Congestion detected by lung ultrasound (LUS) through B-lines is related to prognosis in HF (heart failure) patients; performing it after a physical stress test can detect congestion even earlier. The 6-minute walk test (6MWT) is a submaximal stress test used to assess response after treatment, functional capacity, and prognosis in HF patients. There are no studies evaluating the use of lung US after the 6MWT. Aim: To evaluate the correlation of the number of B-lines on LUS before and after the 6MWT with the distance covered in the stress test in outpatients with heart failure with reduced ejection fraction (HFrEF). Methods: It is a cross-sectional analytical study with prospective inclusion of patients from three HF outpatient clinics. Inclusion criteria were: age >=18 years, to have the diagnosis of HF for at least 6 months and to have echocardiogram with ejection fraction <40%. Patients were submitted to the LUS before and after 6MWT. Results: From September 15, 2020 to November 30, 2021, 188 patients were included in the study. The mean age of the patients was 61.83 years (+-12.13 years); most patients were male (63.8%); the median left ventricular ejection fraction was 31.73% (interquartile range 25-75% [IQR] 28-37%); the most prevalent etiology of HF was ischemic (52.7%); the median number of B-lines was 3 (IQR 1-9) at rest and 6 (IQR 2-13) after submaximal stress; the median distance covered on 6MWT was 363.5 m (IQR 270-436). The distance covered on the 6MWT was inversely correlated with the total number of B-lines after submaximal stress (r = -0.235; p = 0.001) and at rest (r = -0.253; p = 0.001). Conclusion: The distance covered on the 6MWT was inversely correlated with the total number of B-lines after submaximal stress and at rest in outpatients with HFrEF. There was no significant difference between stress and rest B-lines. More studies, with prognostic follow-up, are needed to assess whether LUS associated with the 6MWT adds more benefit in the evaluation of patients with HF. 112049 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Evaluation of the Behavior of the Number of Cases of Chagas Disease in Brazilian Regions between 2016 and 2020 ANNA LUIZA ALVES DE OLIVEIRA MIRANDA1, Maria Eduarda dos Santos Lopes Vasconcelos1, Jose Pedro da Silva Sousa1, Jose Wilker Gomes de Castro Junior1, Beatriz Siems Tholius1, Evaldo da Costa Sa Borges de Rezende2, Matheus Rocha Maia1 (1) Centro Universitario do Estado do Para (CESUPA); (2) Universidade Federal do Para (UFPA) Introduction: Chagas disease (CD) is a zoonosis caused by the protozoan Trypanosoma cruzi, whose vector is a hematophagous triatomine. The transmission mechanisms are vectorial, oral, vertical, accidental, by blood transfusion or organ transplantation. Objective: To analyze the behavior of the annual number of cases of CD in Brazilian regions, between 2016 and 2020. Methods: Descriptive, retrospective, and quantitative study, from 2016 to 2020. Data were extracted from the Notifiable Diseases Information System (SINAN) from the Department of Informatics of the SUS (DATASUS), with the variables: sex, probable mode of infection and confirmation criteria. Results: From 2016 to 2020, were 1,662 new cases of CD in Brazil, 1,573 (94%) in the North, 75 (9%) in the Northeast, 7 (0.5%) in the Southeast and 7 (0.5%) Midwest. Regarding the year of detection, 359 (22%) occurred in 2016, 338 (21%) 2017, 384 (23.5%) 2018, 385 (23.5%) 2019 and 157 (10%) 2020. Gender, 897 (54%) were men and 765 (46%) were women. According to the probable mode of infection, 97 (6%) were: vectorial, 5 (0.3%) vertical, 5 (0.3%) accidental, 1,405 (84.4%) oral and 150 (9%) ignored. According to the confirmation criteria, 1,579 (95%) were performed by laboratory, 45 (2.5%) clinical-epidemiological, 7 (0.5%) remained under investigation, and 31 (2%) were ignored. Conclusion: There was an increase in the annual number of CD cases in Brazil in the years studied, with a predominance in the North region, men, browns and oral mode of infection, the diagnosis being confirmed through laboratory tests, they are the research of the parasite and the identification of antibodies in the serum. In recent years, the average worldwide incidence of CD per year has remained around 30,000 cases/year, with Brazil being an endemic area, especially in the state of Para, corresponding to 74% of cases in the five years evaluated, a state that has culture of consumption of acai and sugarcane juice, which are the main sources of food contamination by deposition of feces of infected triatomines or crushing of the same during processing. In this way, it is evident that acting in the awareness of the population about the consumption and treatment of food, as well as greater participation of inspection in the places where potentially contaminated food is sold, contributes to the prevention of Chagas disease, a serious pathology that can lead to cardiomyopathy. and progress to heart failure. 112052 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Screening for Systemic Arterial Hypertension in Pre-Elderly and Elderly in an Amazon Riverside Community GABRIEL IRISMAR RODRIGUES SCHWAMBACK1, RAIMUNDO BENICIO DE VASCONCELOS NETO1, Rebecca Shaiane Soares Nunes Rivoredo1, Ana Caroline Leite Guedes1, Jade Gomes da Costa Medeiros1, Lucas Vieira Amorim1, Archimedes Fernandes Alves de Santana1, Byron Maia Feitosa1, Maria Eduarda Brotto de Souza1, Renata Goncalves Silva Santos1, Orisman Martins de Souza Rocha Filho1, Fernanda Gabry Scazuza Gomes1 (1) Centro Universitario Sao Lucas - UNISL Introduction: Systemic Arterial Hypertension (SAH) is considered a chronic non-communicable disease (NCD) of insidious onset and that, if not diagnosed and treated, evolves as a precursor to other cardiovascular pathologies. With the aging process, it is common for this CNCD to become more frequent in the population, given the physiological processes of the heart that are affected by time and harmful lifestyle habits. Thus, tracking the number of pre-elderly people (between 55 and 64 years old) and elderly people (over 65 years old) with SAH contributes to highlighting the situation in which a given population finds itself, in addition to providing data for later health interventions. Objectives: To estimate the prevalence of SAH in pre-elderly and elderly people residing in a riverside community in the Western Amazon, Brazil. Methods: This is a cross-sectional, quantitative study carried out with individuals aged between 55 and 87 years, regardless of gender, residing in a riverside community in Porto Velho, Rondonia, Brazil. Data collection was made possible by the application of an individual epidemiological questionnaire during home visits. The analysis was performed by applying the prevalence ratio and the Mantel-Haenszel chi-square test, with statistical significance p < 5%. Results: Data from 58 individuals were analyzed, of which 30 (52%) were male and 28 (48%) were female. We found 35 (60.3%) individuals with an informed prior diagnosis of SAH, with a mean age of 69 years, ranging from 55 to 87 years. As a risk factor for SAH, females have a prevalence ratio equal to 1.4 (variation from 0.93 to 2.19) compared to males (p = 4.9%). Conclusion: SAH is a highly relevant disease to be studied in elderly populations, especially with regard to tracking this CNCD in remote communities, given the strong association between cardiovascular diseases and advanced age. The data point to a prevalence of more than 60% of respondents, an expected value for pre-elderly and elderly people, reinforcing the importance of monitoring the cardiovascular health of this population. No associations were found between sex and SAH in this study. 112054 Modality: E-Poster Scientific Initiation - Non-case Report Category: PSYCHOLOGY Investigation Into the Influences of Depression on the Management of People with Heart Disease: A Systematic Review LUMA MARIA FAVACHO BORDALO1, Yasmin Cavalleiro de Macedo Maranhao1, Paula Cordeiro Aguiar de Almeida1, Leticia Mariana Gomes Santiago Freire1, Glendse Giovanna Costa Pinheiro1, Luma Fleury de Figueiredo1, Ana Julia Farache Cabral1, Heullem Uyhara da Silva Amorim1, Israel Figueira Lemos1, Maria Eduarda Dantas da Veiga1, Juliana Tavares de Sousa1, Erick Clayton Goncalves Feio1 (1) Universidade do Estado do Para Introduction: In analyzing heart diseases, multiple factors are considered, such as the presence of Major Depressive Disorder (MDD) since pathologies can establish, among themselves, a syndemic relationship capable of aggravating the patients' condition. Therefore, the investigation of the impacts of this scenario on the quality of life of those affected is essential to establish improved management measures. Objective: To verify the influence of depression in the treatment of people with heart disease. Methods: The methodology was based on the PRISMA protocol and searches were conducted in the Virtual Health Library (VHL) database using the descriptors "treatment", "heart diseases" and "depression"; observational studies, published between 2017 and 2022 in Portuguese and English were included. Those that do not relate to the central question, do not have full text available on the platform, or were duplicated were excluded. Results: 6042 articles were obtained with the descriptors. After applying the filters 134 were selected and after deep reading, 4. The first literature indicated that among patients with cardiovascular disease (CVD), there is a prevalence of major depressive disorder (MDD) two or three times greater than the general population and that the possible mechanisms that justify this syndemic relationship between MDD and CVD include dysfunctional neurohormonal and autonomic nervous system effects, brain-derived neurotrophic factor and behavioral factors, as well as inflammation and increased platelet aggregation. Confirming the existence of this relationship, another article points out that individuals with MDD are more likely to develop CVD and associated cumulative diseases, in addition to being more vulnerable to subsequent mortality. Two articles show that patients with CVD and MDD represent a significantly higher financial cost for follow-up than patients without MDD. The fourth study indicates that motivational interviews and interventions based on the transtheoretical model are shown to be effective in improving depressive symptoms associated with coronary atherosclerosis. Conclusion: Patients with CVD are more likely to have MDD and both health conditions have an imbricated relationship, in which the worsened manifestation of one tends to cause the same scenario in the other. In addition, TDM and CVD, when together, result in more financially expensive treatment. 112068 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Cross-Sectional Study of Deaths Caused by Acute Myocardial Infarction in Brazil, Divided by Regions (2020) VINICIUS MACIEL VILHENA1, Aurea Nathallia Gomes de Souza1, Bianca Paula Miranda Martins1, Camila Silva de Oliveira1, Cecilia Rodrigues Viana1, Larissa Silva Ferreira1, Luiz Felipe Facanha Ramos1, Marcos Roberto Marques da Silva Junior1, Reny Wane Vieira dos Santos1 (1) Universidade Federal do Amapa Introduction: Acute myocardial infarction is an ischemic lesion of the heart muscle due to a severe alteration in the functioning of the coronary arteries, leading to decreased blood flow to the myocardium and consequent tissue necrosis. This event can lead to death if not diagnosed urgently. In addition, this disease represents one of the main causes of death in Brazil and in the world, with serious consequences for mortality, morbidity and cost to society. Objective: To analyze the epidemiological profile of deaths caused by acute myocardial infarction in Brazil during 2020. Methods: Epidemiological study with a cross-sectional design of mortality from acute myocardial infarction in Brazil during 2020, divided by regions. The data presented were extracted from the DATASUS database, operated by the Health Department. Results: According to the data collected, in Brazil in 2020 there were 90.465 deaths caused by acute myocardial infarction. With a mortality rate of approximately 42.72 per 100.000 inhabitants. Among the Brazilian regions, the South region had the highest mortality rate, approximately 46.85 per 100,000 inhabitants, followed by the Northeast region with a rate of 43.67. The northern region had the lowest mortality rate, approximately 29.78. Regarding the states, those with the highest rate were: Mato Grosso do Sul (65.67), Rio de Janeiro (61.68) and Piaui (56.83). Those with the lowest rate were: Amazonas (19.03), Amapa (22.28) and Distrito Federal (23.63). According to sex, 53.925 men and 36.534 women died from acute myocardial infarction in 2020. Conclusions: It was observed that Brazil presents different situations in relation to mortality from acute myocardial infarction in each region and state. It is possible to reflect on the quality of life in each region and the possible risk factors related to this disease and how this can change the data, which should be further studied. In addition, there is the possibility of underreporting in regions with lower infrastructure conditions for the collection of these data, which can make the management of this disease difficult. 112088 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT COVID-19 Vaccine-Associated Takotsubo Cardiomyopathy: A Systematic Review VINICYUS EDUARDO MELO AMORIM1, Ana Cecilia Araujo Cabral2, Leticia Fagundes do Nascimento Silva3 (1) Faculdade Pernambucana de Saude; (2) Faculdade Pernambucana de Saude; (3) Faculdade Pernambucana de Saude Background: The coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has negatively affected millions worldwide. There is an urgent need to advance vaccine campaigns, however, the adverse effects of these vaccines remain unclear. Some patients have reported chest pains and atypical symptoms characteristic of Takotsubo cardiomyopathy (TCM) shortly after receiving the vaccine. TCM is often triggered by intense emotional stress. It characteristically presents with features that mimic acute myocardial infarction. Objectives: To assess the relationship between Takotsubo Cardiomyopathy and the Covid-19 vaccine through a systematic review. Methods: The bibliographic search was performed, using the PRISMA protocol, from articles published in PubMed from January 2021 to April 2022 associating the key terms: Takotsubo Cardiomyopathy, Vaccination and COVID-19. From this, 154 articles were found. The articles included fulfilled the criteria for discussing the arising of TCM after vaccination for covid-19. Articles that only approach the increase in the incidence of TCM during the pandemic were excluded. Results: After selection, nine case reports and one case series were identified through this search process totalling eleven patients. The median age of the 11 TCM patients was 62,27 years, with most being female [81,8%]. Vaccines received by patients were Pfizer-BioNTech Covid-19, mRNA-1273 and ChadOX1 nCOV-19. Ten patients developed atypical symptoms within the first 10 days post-vaccination. The most common symptoms were: body pain, chest pain, chest pressure, dyspnea, palpitation, malaise, nausea, fatigue, sweating, vomiting and hypotension. Eight patients had comorbidities, but only 1 had a previous history of Covid-19 infection. All patients had positive troponin and electrocardiogram changes, with a negative T wave being the most common finding. Coronary angiography and X-ray were used to rule out other possible diagnoses. Cardiac magnetic resonance, transthoracic echocardiography and ventriculography were used to diagnose TCM and the most common findings were left ventricular akinesia and hypokinesia, apical ballooning and ejection fraction reduction of less than 50%. Conclusion: Despite the similarity between the cases, the causality of TCM triggered by vaccination cannot be proven, due to the small sample size; however, it appears to be the most likely cause, as the onset of symptoms occurred very soon after vaccination. 112100 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Left Atrial Appendage Occlusion During Cardiac Surgery as a Preventive Strategy for Stroke in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis LETICIA RIBEIRO DO VALE1, Elias Pereira de Lisboa2, Pedro Guido Rocha de Almeida3, Vitor Hugo Soares Rosa4, Maria Isabel Fortunato Cavalcante5, Felipe Eduardo campos da Silva6, Lucas Amaral da Silveira7, Elany Maria Ferreira Portela8, Helvecio Teixeira Mazon Junior9, Giovanna Vinhal Reis10, Brenna Pinheiro Zuttion11, Leticia Ribeiro do Vale1 (1) Leticia Ribeiro do Vale; (2) Elias Pereira de Lisboa; (3) Pedro Guido Rocha de Almeida; (4) Vitor Hugo Soares Rosa; (5) Maria Isabel Fortunato Cavalcante; (6) Felipe Eduardo campos da Silva; (7) Lucas Amaral da Silveira; (8) Elany Maria Ferreira Portela; (9) Helvecio Teixeira Mazon Junior; (10) Giovanna Vinhal Reis; (11) Brenna Pinheiro Zuttion Introduction: Atrial fibrillation (AF) results from abnormalities in electrical conduction. The left atrial appendage (LAA) is the most recurrent site for thrombus formation and its occlusion is an intervention that reduces the risk of stroke. Objective: To compare the results of LAA occlusion during cardiac surgery in patients with AF and the development of Ischemic Stroke. Method: Systematic review using the PRISMA methodology and the PICO criteria in the MEDLINE, COCHRANE and LILACS databases, using the keywords "Atrial fibrillation", "Left Atrial Appendix" and "Thromboembolism" to identify relevant articles. Five publications were considered for the meta-analysis, involving 15,595 patients with AF who underwent surgical cardiac interventions. The odds ratio (OR) values and their respective 95% confidence intervals (95% CI) were calculated using RStudio. Results: Of the five studies, one presented an OR value greater than 1, rejecting the hypothesis. The overall OR was 0.68 [95% CI 0.57; 0.82]. The I2 heterogeneity measure was 0%, a value considered as low heterogeneity. Publication bias was assessed using the funnel plot. Conclusion: Patients with AF who underwent LAA occlusion reduced the chances of developing ischemic stroke when compared with patients with AF who did not undergo the procedure. This study presents evidence in favor of performing the LAA occlusion procedure as an effective alternative to reduce the risk of stroke. 112094 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Heart Failure Induced by Antineoplastic Treatment: A Systematic Review DAVI GABRIEL BARBOSA1, Marcella Oliveira Monte Santo2, Paola Bitar de Mesquita Abinader3, Daniel Oliveira da Costa1, Afonso Moraes Melo Junior3, Camila Rodrigues Maciel3, Joao Lucas Watrin Braga3, Bruna Freitas Vinagre3, Igor Lucas Farias Lima1, Luig Matias Barreiros Pires3, Wadilla Fiuza da Silva2, Luis Eduardo Werneck de Carvalho4 (1) Universidade do Estado do Para - UEPA; (2) Universidade Federal do Para - UFPA; (3) Centro Universitario do Para - CESUPA; (4) Sociedade Brasileira de Cancerologia - SBC Introduction: Antineoplastic chemotherapy consists in the administration of drugs that act at the cellular level, destroying tumor cells. Because they act without specificity, they can generate undesirable effects, such as cardiotoxicity; presenting as main damages the higher frequency of moderate or severe heart failure associated with systolic or diastolic ventricular dysfunction. Objectives: To analyze the induction of heart failure in patients on antineoplastic treatment by searching for scientific evidence in the database literature. Methods: A systematic review was conducted through a bibliographic search of articles, using the Virtual Health Library database, whose filters were: articles published in the last 5 years, published freely and in full, and randomized clinical trials. The descriptors used comprised (Heart Failure) AND (Antineoplastics) AND (Cardiotoxicity) and the exclusion criteria were case reports and other systematic reviews. PICO and PRISMA methodology was employed. Results: The use of trastuzumab can lead to decreased left ventricular function and moderate or severe HF. There is a decline in LVEF with improved survival with the use of ACEI and beta-blockers, reducing mortality and patient hospitalization. Crizotinib showed few events associated with HF. Anthracycline, used in first-line lymphoma treatment increases the risk of CHF in patients with no prior history of heart disease, particularly when treatment courses with more than 6 cycles of R-CHOP/CHOEP. The expression of TLR2 and TLR3 biomarkers is down-regulated, respectively, in patients treated with doxorubin, causing cardiac dysfunction. ACE inhibitors in anthracycline-induced cardiotoxicity, did not develop arrhythmia or heart failure, and enalapril acted in reducing cardiac toxicity after anthracycline administration. Conclusion: It is inferred that the antineoplastic drug with the highest relation to HF is anthracycline. However, the group of ACE inhibitors and enalapril decrease the cardiotoxicity of anthracycline. Moreover, trastuzumab is related to the onset of moderate or severe HF, and the ACE inhibitor drug groups IECA and beta-blockers decrease mortality in these patients. Doxorubin has predictive markers: TLR2, up-regulated, and TLR3, down-regulated. 112099 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Mortality from Cerebrovascular Disorders in Women in the Northern Region of Brazil from 2010 to 2020 GABRIELLY CARVALHO LEAO1, Gabrielly Carvalho Leao1, Saul Rassy Carneiro1, Vando Delgado de Souza Santos1, Bruno Patricio dos Santos Oliveira1 (1) Universidade Federal do Para Introduction: Cerebrovascular Disorders encompass several diseases with clinical manifestations resulting from the interruption of brain blood flow, which can manifest in an ischemic way, usually linked to circulation obstruction, or in a hemorrhagic way, when there is vascular rupture. In view of the wide occurrence of deaths and permanent sequelae that such diseases generate, investigation and understanding of them become indispensable. Objectives: To identify and analyze the epidemiological profile linked to the mortality of female individuals due to Cerebrovascular Disorders in the northern region of Brazil, from 2010 to 2020, as well as to associate it with regional factors of a social and economic nature. Methods: This is an observational and cross-sectional study, which used mortality records in cases of cerebrovascular diseases in northern women, between January 2010 and December 2020, obtained through the Departamento de Informatica do Sistema Unico de Saude (DATASUS), using the variables age group, color, schooling and place of occurrence. Results: The data gathered showed the occurrence of 30,490 deaths of women from cerebrovascular diseases in the region in question during the period considered, a value that corresponds to 45.94% of the total deaths of this category in the north of Brazil. Regarding the profile of these northern women, it should be noted that 79.96% of them were aged over 60 years. In addition, 33.47% of these women did not have any complete levels of education and 66.35% declared themselves to be brown. Finally, regarding the place of death, 74.55% took place in hospital settings. Conclusion: Thus, it is evident that cerebrovascular disorders predominate in the female population in disadvantaged socioeconomic situations, especially elderly brown women, without a degree of education, with low income and possibly without access to health surveillance and primary prevention mechanisms (such as encouraging and subsidizing healthy eating and physical activity). In addition, the high death rates in the hospital context indicate the contribution of the diseases analyzed to the burden of the health system, reinforcing their severity and the need for preventive actions, in order to guarantee the well-being and longevity of women northerners. 112104 Modality: E-Poster Scientific Initiation - Non-case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Population at Risk for Heart Failure in the Amazon Basin BIANCA VASCONCELLOS RODRIGUES LOPES1, Luisa de Oliveira Pereira Vila Nova Ramalho1, Laura Cordeiro Gomes3, Philip Brainin2, Anna Engell Holm2, Karine Oliveira Lima1, Isabelle Victoria Martins Vieira1, Marliton Vinicius Pedrosa Evangelhista1, Luan Oliveira Matos1, Iara Fernanda Vasconcelos de Oliveira e Silva1, Tor Biering-Sorensen2, Odilson Marcos Silvestre1 (1) Federal University of Acre; (2) Herley-Gentofte University Hospital; (3) University of Sao Paulo Introduction: Neglected diseases, less access to health services and socioeconomic factors makes the Amazon Basin a vulnerable area for heart disease. There is no data concerning the risk for developing heart failure in this setting. Aim: To assess the population at risk for developing heart failure in the Amazon Basin. Methods: We performed a cross-sectional study in the Brazilian Amazon Basin. Patients were classified as at risk for HF according to the American College/American Heart Association staging system. For stage A, we considered the presence of at least one of the following factors: hypertension, diabetes, BMI > 30 kg/m2, hypercholesterolemia, moderate or intense alcohol use, smoking and history of rheumatic fever. We compared those at stage A with those with no risk factors (table). Results: The mean age was 39 years and 47% were male. 70% of all patients were in stage A for HF. Among those, 29% had hypertension, 4% had diabetes, 24% were obese, 38% had hypercholesterolemia, 11% consumed alcohol at moderate or intense level, 11% smoked and 6% had a history of rheumatic fever. HF risk participants had lower educational levels, 214 (27.7%) participants did not complete elementary school vs. 43 (13.4%) in out of risk population (p < 0.001). A total of 385 (49.9%) stage A patients have lived in rural areas for the most part of their lives against 121 (37.7%) at non-risk group (p < 0.001). Median income was lower in stage A [median (IQR) R$ 360.0 (175 to 700.0)] when compared to the other group [median (IQR) R$ 400.0 (240.0 to 800)] (p < 0.004). Conclusion: Most of Amazon Basin population is at risk for developing heart failure. Patients at stage A are older, have lower income and educational levels and have lived in rural areas for the most part of their lives. 112112 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Stent Implantation for the Treatment of Carotid Aortic Coarctation in Infants LIVIA FARIAS DE HOLANDA FURTADO1, Patricia Oliveira Lima de Macedo1, Lais Vieira Araujo1, Joao Victor Bezerra Nunes1, Abel Belarmino de Amorim Neto2, Lara Andrade Dantas2, Ranise Nunes Pereira Moura2, Daniel Marcelo Silva Magalhaes2, Carlos Marximiliano Alves de Oliveira2, Juliana Sousa Soares de Araujo1, Claudio Teixeira Regis3, Fabricio Leite Pereira2 (1) UFPB - Universidade Federal da Paraiba; (2) Hospital Metropolitano Dom Jose Maria Pires; (3) Complexo Pediatrico Arlinda Marques Introduction: Coarctation of the aorta is a congenital heart disease in which there is narrowing of the aortic isthmus. Stenting for treatment is well established in adults and in children over 25 kg. However, in younger children the usual treatment is surgery or balloon recoarctation. Currently, this technique has been used in selected cases. Objective: To demonstrate the early results of stent implantation for the treatment of carotid coarctation in infants. Methods: This is a cross-sectional, observational, retrospective study of a case series of stenting in carotid coarctation in a public hospital in Paraiba. Results: 4 infants underwent carotid stenting in infants with a mean age of 110 days (22 days to 12 months), mean weight 5.3 kg (2.9 to 10.6 kg) all male, and with another cardiac alteration. In the first case, the coarcted area increased from 2.6 to 7 mm; the second increased from 1.3 to 6 mm; the third increased from 3 to 8 mm, and the fourth increased from 3.4 to 8.5 mm. Thus, the pre-treatment mean was 2.58 mm and became 7.38 mm, with the size of the balloon chosen by measuring the abdominal aorta and the aortic arch. Only 1 patient presented as a complication a small aortic dissection, of expectant management. All patients presented normalization of the abdominal aortic flow in the control echo. Conclusion: Stent implantation proved to be effective and safe in the short term, and may be a treatment option also at this age. However, further long-term studies are needed to monitor the effectiveness of the technique in terms of reinterventions required due to somatic growth of patients. 112116 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIO-ONCOLOGY Antineoplastic Protocols in Cardio-Oncology: Updates from the Past 5 Years PAOLA BITAR DE MESQUITA ABINADER3, Marcella Oliveira Monte Santo1, Ana Josefina Goncalves Salomao3, Davi Gabriel Barbosa2, Joao Lucas Watrin Braga3, Leandro Lourenco Silva Monteiro2, Manuela pedreira da Cruz Rocha3, Vinicius Queiroz Silva2, Alexandre D'Annibale Cartagenes2, Luis Eduardo Werneck de Carvalho4, Luiz Fernando Leite da Silva Neto2 (1) UNIVERSIDADE FEDERAL DO PARA (UFPA); (2) UNIVERSIDADE ESTADUAL DO PARA (UEPA0; (3) CENTRO UNIVERSITARIO DO PARA (CESUPA); (4) ONCOLOGICA DO BRASIL Introduction: Antineoplastic protocols guarantee standards and criteria to treat different neoplasms, based on effectiveness and scientific evidence. Henceforth, it is possible to define the degree of validity in therapeutic category. In the cardio-oncology field, adopting these protocols is essential, since some pharmacological interventions can be cardiotoxic, such as the use of anthracyclines, becoming necessary the regulation of therapies for these pathologies. Objective: Analyzing antineoplastic protocols in cardio-oncology searching for scientific evidence and database updates. Methods: This is a systematic literature review with descriptive collection and a qualitative approach to data on antineoplastic protocols in cardio-oncology, available in the BVS database. The search formula used was: Antineoplastic Protocols AND Cardiac Neoplasms. Studies that presented a 5 years maximum gap since their publication, and published in completion and in English, were selected. Exclusion criteria were: other types of studies. The data extraction and synthesis strategy followed the PICO and PRISMA guidelines. Results: 795 studies were found on the search platform with the descriptors, 113 remained after initial filtering, 40 of these were applicable in the inclusion criteria, 4 studies were selected for analysis. In the case of cardiac rhabdomyomas related to tuberous sclerosis, surgery is indicated, but it has a high mortality rate. Regarding pharmacological treatment for them, there are studies indicating that prolonged treatment with sirolimus has shown positive results and has been shown to be more beneficial in male patients. In the case of ventricular fibromas and cardiac myxomas, surgical resection with cardiopulmonary bypass showed benefits and a high survival rate with few complications. Conclusion: In this viewpoint, it is noted a beneficial relationship in the use of antineoplastic drugs in patients affected by cardiac tumors, especially in male subjects, with the treatment being faster; aged over 4 years and fewer cardiovascular surgeries. Thus, even though the number of studies on this condition is scarce, there is an important possibility of pharmacological intervention in cardio-oncology services that needs further studies. 112123 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Comparison of Electrocardiographic Changes Consistent with Pericarditis in Patients Undergoing Posterior Pericardiotomy During Coronary Artery Bypass Graft Surgery - A Randomized Double-Blinded Study GUSTAVO GUIMARAES OLIVEIRA3, Gustavo Guimaraes Oliveira3, Carolina Maria Vianna Guimaraes2, Jackson Brandao Lopes2, Taina Teixeira Viana1, Diego Moreira Arruda1 (1) Hospital Ana Nery - HAN; (2) Universidade Federal da Bahia - UFBA; (3) Escola Bahiana de Medicina e Saude Publica - EBMSP Background: Posterior pericardiotomy (PP) is a surgical technique in which a 4 cm incision is made in the pericardium in order to avoid complications in the postoperative period (PO) of cardiac surgeries, such as pericardial effusion (PE) and atrial fibrillation (AF). There are, however, few studies addressing the presence of electrocardiographic findings of pericarditis in patients undergoing this procedure. Objective: Compare the presence of electrocardiographic alterations compatible with pericarditis, AF and PE in the PO period of myocardial revascularization between the groups. Methods: A double-blinded, single center, randomized study, conducted by Hospital Ana Nery - Bahia, with a sample size of 30 patients. Patients were randomized into two groups: intervention group (submitted to PP) and control group (CG), which did not undergo PP. Data collected for the study included pre-, postoperative data. Results: In the sample, 62.5% are men, the PP group was composed by 66% male and the CG 80%, while the mean age of the study was 62.4 +- 8.9 years. The patient's EUROSCORE II had a median of 0.76 with a maximum of 2.5 and a minimum of 0.5. All the patients analyzed used the internal mammary artery in the surgery, while 26.7% of the CG used double mammary against 6.7% in the PP group. The radial artery was used in 33.3% of patients in the PP group and 53.3% of the CG. In the PP group, a frequency of 6.7% of AF was observed in the PO, while in the CG 0.0% (p = 0.30). Regarding PE, there was a 26.7% incidence in the PP group and 40.0% in the CG (p = 0.43). Electrocardiographic findings of pericarditis were identified in 6.7% of patients in the CG and 20.0% of the PP group (p = 0.28). There was one death in the study that occurred in the CG on the 20th postoperative day (p = 0.30). Conclusion: Although a lower incidence of PE was found in the PP group, it was not statistically significant. It was also not possible to identify a statistically significant difference in the occurrence of AF between the groups or of electrocardiographic changes compatible with pericarditis. Due to the low incidence of events in this study, the N was not powerful enough to identify the statistical differences already reported in the literature, which makes us believe that a larger sample is needed to corroborate or disprove previously published data. 112124 Modality: E-Poster Scientific Initiation - Non-case Report Category: DYSLIPIDEMIA Prevalence of Left Ventricular Diastolic Dysfunction Among Patients with Familial Hypercholesterolemia Under Primary Prevention AMANDA PEREIRA MATOS1, Rogerio Krakauer2, Renato Jorge Alves2 (1) Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo; (2) Santa Casa de Misericordia de Sao Paulo Background: Familial Hypercholesterolemia (FH) is a disorder characterised by an increased serum LDL-cholesterol level (LDL-c > 190 mg/dL). It represents a high cardiovascular risk and leads to complications that can compromise the ventricular myocardium function. There are no studies on left ventricular (LV) diastolic function in patients with FH. The early detection of subclinical morphological changes could contribute to a more effective prevention strategy. Purpose: This study aimed to obtain the prevalence of diastolic dysfunction among patients with FH under primary prevention (PP) and to epidemiologically compare PP and secondary prevention (SP) in patients with FH. Methods: We performed a cross-sectional study with 42 patients with FH over 18 years old of a dyslipidemia outpatient clinic of a tertiary hospital. The patients were divided into two groups: PP and PS. We excluded those who, at the time of the echocardiographic assessment, presented: ejection fraction less than 50%, LV regional wall motion abnormality, significant valve dysfunction, cardiac arrhythmia, pericardial effusion or unavailable information to determine LV diastolic function. Each exam was performed on the same machine and analysed by the same physician. Results: Out of 42 patients, 9 were excluded. Of a total remaining 33, 12 were included in the PP group and 21 in the SP. Therefore, 36,4% (12/33) underwent the transthoracic echocardiogram exam for diastolic function assessment. After exams' analysis: 75% (9/12) of the patients had normal diastolic function, 8.3% (1/12) indeterminate function and 16.7% (2/12) presented grade I diastolic dysfunction. Of those with normal function, one had diabetes and one, grade I obesity. Of those with the dysfunction, one had diabetes and one, diabetes and grade III obesity, both elderly. By comparing the two groups: PP had an average age of 60.5 years old and SP 67 years old; PP 91.7% women and SP 71.4%; PP 25% and SP 38.1% diabetes; PP 50% and SP 90.5% arterial hypertension (p = 0,015). Conclusions: Patients with FH under PP did not show significant changes in LV diastolic function (low prevalence of grade I dysfunction only). Furthermore, patients under SP showed a higher frequency of arterial hypertension. However, new studies must be carried out, with a higher number of patients, for better clarification. 112125 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Preoperative Electrocardiographic Parameters as Predictors of Atrial Fibrillation in the Postoperative Period of Cardiac Surgery DAVID CESARINO DE SOUSA1, Fabio Antonio Serra de Lima Junior1, Renan Furtado de Almeida Mendes1, Andre Loureiro Fernandes1, Ana Beatriz Venancio de Paula Bezerra1, Raphael Patrik Borges da Costa1, Tiago Lucena de Brito Pereira2, Joao Bosco Ferreira Gadelha2, Isaac Newton Guimaraes de Andrade1, Andre Telis de Vilela Araujo1 (1) Universidade Federal da Paraiba; (2) Clinica Dom Rodrigo Introduction: Postoperative atrial fibrillation is responsible for important postoperative morbidity and mortality, and the ability to predict it could allow prophylactic measures and intensive monitoring in patients at higher risk. Objectives: To relate preoperative ECG findings of patients undergoing cardiac surgery with the occurrence of postoperative arrhythmias, and compare the results with those found in national and international studies. Methods: A longitudinal observational study was conducted with patients undergoing cardiac surgery between 2019 and 2021 in a cardiology referral hospital in Joao Pessoa. postoperative 12-lead electrocardiogram data were collected and processed, in addition to patients' constitutive and surgical data. Results: A total of 105 patients were observed, with the presence of supraventricular extrasystole (2 vs. 0 cases, p = 0.017), P-wave amplitude (0.993 +- 0.8426 mV vs. 0.318 +- 1.1467 mV, p = 0.015), the Morris index (-94.286 +- 78.2849 mV.ms vs. -36.951 +- 94.7297 mV.ms, p = 0.023) and the presence of left ventricular overload (6 vs. 12 cases, p = 0.015). Conclusion: The presence of supraventricular extrasystole, P wave amplitude, Morris index, and the presence of electrocardiographic criteria of left ventricular overload were associated with a higher risk of developing postoperative atrial fibrillation. Larger samples may reveal yet other significant predictor variables. 112127 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Assessment of Adherence to Hypertension Treatment in People with Depressive Symptoms: A Systematic Review ISRAEL FIGUEIRA LEMOS1, Alice Marcely dos Santos Tunas1, Rafael Malcher Meira Rocha1, Giovanna Lopes Evangelista2, Ronaldo Monteiro Veras3, Guisela Gabriela Silveira de Souza1, Maria Giovanna Trindade Rocha1, Lucas Matheus Marinho de Miranda1, Maria Eduarda Dantas da Veiga1, Juliana de Sousa Tavares1, Erick Clayton Goncalves Feio1, Luma Maria Favacho Bordalo1 (1) Universidade do Estado do Para; (2) Centro Universitario do Para; (3) Universidade Federal do Para Introduction: According to the new Brazilian Hypertension Guidelines (2020), the main reason for inadequate control of hypertension is noncompliance with long-term treatment. Some factors such as the absence of symptomatology and the requirement for continuous treatment, as well as changes in habits, are important in this statistic. Depression, however, can make the patient reduce his health care for a psychic issue, by the symptoms of discouragement, easy fatigue, and need for greater effort to do things. Objectives: To evaluate the relationship between adherence to treatment for hypertension and depressive symptoms. Methodology: This is a systematic literature review, it was used as a database the Virtual Health Library (VHL), with the descriptors "Hypertension", "Depression" and "Treatment Adherence" between the years 2017 and 2022, in English and Portuguese, published free and fully, selected through the PRISMA method. Where articles that did not address the relationship to be evaluated and literature reviews were excluded. Results: 283 articles were obtained with the use of the descriptors, 87 with the application of search filters, after detailed reading, 8 met the objectives of the study. From the literature, it is observed that depression negatively influences adherence to hypertension treatment. The chance of a patient being at the target pressure increases significantly with increased adherence to treatment for depression. In one study, with women only, depression was more reported by patients with worse adherence to AH treatment (p = 0.026). However, no differences in depression symptoms were observed between adherent and non-adherent patients seen in an emergency room. Hypertensives with depressive symptoms have a significantly higher relative risk of treatment noncompliance. In this sense, the negative impact of depression on the capacity for self-care and continuation of the prescribed drug therapy is noted, as well as the vulnerability and need for support. Conclusion: In this article, we sought to evaluate adherence and continuity of pharmacological and non-pharmacological treatment for AH in patients with depressive symptoms. Therefore, expanding studies that propose and evaluate strategies for adherence to drug treatment is essential to ensure that individuals remain normotensive, with the potential to reduce the pressure on the health system and represent simultaneous gains in the quality of life of hypertensive individuals. 112134 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Impact of COVID-19 Pandemic on Cases of Cardiac Arrest in Brazil RAFAEL BRACCIO ZAWISLAK1, Mariana Saadi de Azevedo1, Alice Zanetti Dussin1, Thomas Ranquetat Andrade1, Mario Wiehe1 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) Background: Coronavirus disease (COVID-19) is caused by SARS-CoV-2, in which the patient affected has different clinical manifestations. The infection may cause different cardiovascular complications, such as sudden death and cardiac arrest. Besides the pathophysiologic relation of the infection with cardiovascular diseases, these different bad outcomes may also have a social and political component, such as saturation of the health system and loss of patient follow-up. Aims: To evaluate the impact of the Covid-19 pandemic on cases of cardiac arrest with death outcome in Brazil and verify the frequency according to in or out-hospital events. Methods: The data of the last 4 years (2018 to 2021) of deaths due to cardiac arrest were collected using the Mortality Monitoring Panel of the Health Surveillance Department of Brazil. The number of deaths were separated into tables comparing the year of the deaths to location of event. This was conceived as a descriptive study. Results: Pre-pandemic numbers (2018 and 2019) were very similar, averaging them for comparison. The number of deaths of the 2 years before the Covid-19 pandemic were quite similar in age groups and sex. The average number of deaths in the 2018-19 period was 1384, with an increase of 56.21% in 2020 and 130.41% in 2021. The cause of the cardiac arrest was described as sudden death in all periods analyzed. The average number of cardiac arrests in-hospital in the 2018-19 period was 383.5, with an increase of 32.72% in 2020 and 87.48% in 2021. In the 2018-19 period, out-hospital cardiac arrests were at an average number of 1000.5, with an increase of 65.21% in 2020 and 146.87% in 2021. Conclusion: The number of cardiac arrests during the COVID-19 pandemic increased overall, in-hospital as well as out-hospital. This may be related to pathophysiological and social-political components. Events that occurred at home had a significant growth, which may be associated with lockdown protocols and difficulty in obtaining basic access to healthcare, possibly related to a hesitation of a possible acquisition of SARS-CoV-2 infection and the overload of hospitals. 112144 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Epidemiology of Deaths by Hypertensive Disease During the COVID-19 Pandemic in Brazil MARIANA SAADI DE AZEVEDO1, Rafael Braccio Zawislak1, Alice Zanetti Dussin1, Rafael Vianna Behr1, Mario Wiehe1 (1) Pontificia Universidade Catolica do Rio Grande do Sul Background: Covid-19, disease caused by Sars-CoV-2, is responsible for the pandemic that generated instability in health systems across the globe and over 66,0000 deaths in Brazil since 2020. There is evidence that arterial hypertension is associated with a more severe course and higher death rates. In addition, control of chronic diseases has been a challenge due to loss of patient follow up and failure to seek medical help in an acute condition. Aims: To convey epidemiological data of the last 5 years of death by hypertensive disease in Brazil and to elucidate its possible relation to Sars-CoV-2 infection and social aspects of the Covid-19 pandemic. Methods: This was conceived as a descriptive study. The Mortality Monitoring Panel of the Health Surveillance Department of Brazil was used to collect the data of the last 5 years (2017 to 2021) of deaths due to hypertensive disease. The data was organized in a table comparing the years pre and post Covid-19 advent. Results: There has been a 19.98% increase in the average of death rates by hypertensive disease in Brazil post covid-19 (years 2020 and 2021) in relation to the years previous to the pandemic that were analyzed (2017-2019). In the years 2017-2019, the average of yearly deaths at home was 21440, while in the years 2020 and 2021 the average escalated to 30146 cases. This shows an increase of 40.6% in the average of deaths at home by hypertensive disease in Brazil post Covid-19. Concerning deaths in hospital, there was an increase of 0.72% in the yearly average post Covid-19. Conclusion: There has been an increase of death by hypertensive disease in Brazil in the years of 2020 and 2021, which coincides with the Covid-19 pandemic. This can be attributed to a significant rise in domicile death rates. Future studies can evaluate factors involved in this increase and, consequently, the forms of preventing it in similar situations. In addition, it must be observed if, in the years following the pandemic, the number of out hospital deaths will return to that of previous years, or if they will still be affected by the pandemic period. 112152 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH Association between the Transfer of Resources via the National Health Fund and the Number of Hospitalizations for Diseases of the Circulatory System VANDO DELGADO DE SOUZA SANTOS1, Saul Rassy Carneiro1 (1) Universidade Federal do Para - UFPA Introduction: Diseases of the circulatory system (DCS) are diseases that affect the heart and blood vessels. Since 1980, they have been the leading cause of death in the world. The analysis of the association between DCS and financial transfers becomes, therefore, essential for the implementation of health policies. Objectives: To analyze the relationship between hospital admissions for DCS and transfer of financial resources via the National Health Fund (NHF) to the northern region of Brazil from 2011 to 2021. Methods: This is a longitudinal epidemiological study carried out with secondary data from the Department of Informatics of the Unified Health System on the number of hospitalizations for diseases of the cardiocirculatory system and the transfer of resources via NHF to the states of the northern region between January 2011 to December 2021. Results: In the analyzed period, a linear regression model was performed, where the transfer of funds via NHF was the independent predictor to analyze hospitalizations for DCS, under the formula y = 69-2.57e-9x. The allocation of resources to the states of the northern region resulted in a significant reduction in the number of hospitalizations (R = 0.748; p < 0.001). A model with the number of family health strategies was used, but it proved to be less adjusted than the transfer of resources, perhaps because the increase in liquidity in the states had a direct impact on the increase in family health teams. Conclusion: There was an inversely proportional relationship between hospitalizations for DCS and financial transfers via NHF. It is important to emphasize the aspect of primary care performance in controlling these indicators, because, with efficient primary care integrated with reference services, the number of hospitalizations for CAD can be reduced. 112170 Modality: E-Poster Scientific Initiation - Non-case Report Category: ANTICOAGULATION Anticoagulant Therapy in COVID-19 Hospitalised Patients REGINA MARIA ALEXANDRE FERNANDES DE OLIVEIRA1, Amanda Pereira Matos1, Ronaldo Fernandes Rosa2, Milton Luiz Gorzoni2, Renato Jorge Alves2 (1) Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo; (2) Hospital da Santa Casa de Misericordia de Sao Paulo Background: Coronavirus disease 2019 has been associated with a prothrombotic state, which puts into question whether a prophylactic anticoagulant therapy could be used to prevent bad outcomes in hospitalised patients since they represent the most severe cases of the disease. However, substantial studies have reported divergent results regarding its benefits and applicability in prevention strategies. Purpose: To explore the incidence of bad outcomes in COVID-19 hospitalised patients that have received Anticoagulants or not. Methods: This retrospective observational study analysed electronic medical records from hospitalised patients with laboratory-confirmed COVID-19 in a large tertiary hospital, between March 2020 and July 2020. The study sample was divided between those who received any dose of anticoagulation (low molecular weight or unfractionated heparin) and those who did not (control group). Our primary outcome was data on mortality, hospital length of stay, need for Intensive Care Unit admission and use of vasoactive medications between the two groups. Results: Of a total 317 patients, 259 (37.8% females, 62.2% males) received Anticoagulants and 58 (37.9% females, 62.1% males) did not. The mortality rate was 49.4% in the Anticoagulant recipient group, and 58.6% in the control group. However, no association could be made between Anticoagulant use and hospital survival (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.8-2.6). The length of hospital stay showed to be similar between the two groups, with an average of 17.8 days (95% CI, 15.3-20.2) for the Anticoagulant group and 16.2 days (95% CI, 9.5-22.8) for the control one. Additionally, lesser need of intensive care could not be associated with blood thinners use (OR 1.6; 95% CI, 0.8-3.1), whereas utilisation of vasoactive medications could (OR 6.5; 95% CI, 3.2-13.3). Conclusion: The findings of our study suggest that the use of Anticoagulants in COVID-19 hospitalised patients is associated with reduced need for vasoactive drugs, with no impact, however, in mortality, hospital length of stay or need for Intensive Care Unit admission. We intend to reexamine the matter with a larger sample of patients. 112160 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Percutaneous Renal Sympathetic Denervation in the Treatment of Hypertension in Patients with Chronic Kidney Disease LETICIA FAGUNDES DO NASCIMENTO SILVA1, Ana Cecilia Araujo Cabral2, Vinicyus Eduardo Melo Amorim3 (1) Faculdade Pernambucana de Saude - FPS; (2) Faculdade Pernambucana de Saude - FPS; (3) Faculdade Pernambucana de Saude - FPS Background: Systemic arterial hypertension (SAH) is a highly prevalent disease that can be both the cause and the consequence of chronic kidney disease (CKD). Chronic kidney disease is defined when the glomerular filtration rate (GFR) is less than 60 mL/min/1.73 m2 for three or more months. In this way, the treatment objective to reduce the progression of kidney disease and cardiovascular risk. Given this, percutaneous sympathetic denervation emerges as a promising new therapy for patients with resistant hypertension when drug therapy fails. In this procedure, ablation of sympathetic fibers is performed through the application of radiofrequency transluminally in the renal arteries. Methods: The study is designed as a systematic review and the articles used were collected through the "PUBMED" and "BVS" platforms and selected according to the PRISMA 2020 protocol. Using the descriptors "Renal denervation", "Hypertension" and "Chronic kidney disease", 105 articles were found. Those with full texts were selected while duplicate articles and that did not directly address the research topic were excluded, leaving 18 articles for review. Results: 18 articles included in the review, including randomized clinical trials, clinical trials, meta-analyses, prognostic study, diagnostic study and etiology study. It was observed an improvement in central pressures and pulse wave velocity, a reduction in systolic pressure was observed in most patients after 3 years of treatment, in addition to renal protection in most of the studies performed. Changes in renal sensory function participate in the maintenance of high vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. However, results from some studies do not show a reduction in the degree of kidney injury. Furthermore, the change in aldosterone level evidenced reaffirms the effect of denervation on the renin-angiotensin-aldosterone system. It is necessary to point out that more clinical trials are needed to assess the safety and reproducibility of the method. Conclusion: Renal denervation is safe for patients with resistant SAH and CKD, with a significant reduction in systolic pressure. However, further studies are needed to assess safety, application advantages and clinical impact. In addition, the mechanisms involved in cardiorenal protection by denervation have not yet been fully clarified. 112171 Modality: E-Poster Scientific Initiation - Non-case Report Category: PSYCHOLOGY Psychological Impacts on Patients who have Suffered from Acute Myocardial Infarction: A Systematic Review MARIA EDUARDA DANTAS DA VEIGA1, Juliana de Sousa Tavares1, Erick Clayton Goncalves Feio1, Luma Maria Favacho Bordalo1, Israel Figueira Lemos1, Amanda de Queiroz Andrade1, Bruno Kaue Rodrigues Vilhena1, Chan David Ribeiro1, Greta Evelin da Silva Mota1, Luis Arthur Moreira Ferreira1, Victor Leno Silva Paes1, Alice Marcely dos Santos Tunas1 (1) Universidade do Estado do Para - UEPA Introduction: Acute Myocardial Infarction (AMI) is a fatal condition, and survivors can present multiple complications related to mental health and quality of life. Thus, the psychological consequences in the individual who suffered AMI interfere with the prognosis of the disease, as there is an association between psychological and biological factors, such as depression and anxiety. Furthermore, these pathologies affect the patient's recovery and life expectancy, increasing the risk of AMI recurrence. Objectives: Identify the psychological impacts on patients after AMI. Methods: Systematic literature review with searches in the Virtual Health Library (BVS) using the descriptors "Psychological distress", "Psychological stress", "Myocardial Infarction" and "Post-traumatic stress disorder". The filters used were original articles, complete and open to public consultation from the last 10 years in Portuguese, English and Spanish. Case reports, notices, editorials, comments and literature reviews were excluded. The PRISMA protocol and the question formulated by the PICO methodology were used. Results: 158 articles were obtained with the descriptors. After applying the filters and detailed reading of the data, 17 articles were included in the present study. The literature pointed to the occurrence of several psychological disorders in patients who suffered from AMI, which made recovery even more difficult. It was pointed out that individuals with Post Traumatic Stress Disorder (PTSD) after infarction had a greater stress response, suggesting an association between PTSD with or without cardiovascular outcomes. Based on this logic, it was found that patients with emotional distress are more likely to die after the AMI. Other results, in addition, indicated heterogeneity of emotional suffering, showing a higher incidence of stress related to youth, poverty and the female gender. Furthermore, high levels of anxiety and depression were noted as predictive factors for mortality and readmission to patients with symptoms of ischemic heart disease. Moreover, professional psychological support is also related to a reduction in the mortality rate and decrease in the recurrence of the cardiac condition. Conclusion: It was identified that the psychological impacts, especially depression and anxiety, are evident in people who have suffered from AMI. In this sense, a more in-depth study of the topic and its relationship with the quality of life of these patients is necessary. 112176 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Chagas Cardiomyopathy and its Prevalence as to the Type of Heart Device and its Outcomes KARLA SANTOS PINTO1, Elias Soares Roseira1, Rafaela Ferreira dos Santos1, Jose Victor de Sa Santos1, GABRIEL SAPUCAIA DA SILVA DE QUEIROZ1, Pollianna Roriz1, Luiz Carlos Passos1, William de Carvalho1 (1) Hospital Ana Nery Introduction: Chagas disease (CD) is the fourth disease with the greatest social impact in Latin America. It is associated with ventricular tachyarrhythmias - an important cause of sudden death (SD). Thus, the implantable cardioverter-defibrillator (ICD) appears as a treatment option for being able to reverse these arrhythmias. Despite this, there are gaps in the indication of the device with a focus on this population, especially in the context of primary prevention. Objective: To describe the profile of CD patients with ICD implantation, prevalence of triggered therapies and post-implantation outcomes. Methods: Descriptive study including patients treated at a tertiary hospital in Salvador-BA diagnosed with Chagas Disease, between January/2021 to April/2022. The variables described were age, sex, NYHA functional class, previous comorbidities, medications, Rassi score (in primary prevention), ICD indication for primary or secondary prophylaxis, number of ICD electrodes, Maggic ICD therapy score and deaths. Results: Sample (n) included 234 CD patients, with a mean age of 60 years, 63.7% of whom were men. The most prevalent previous comorbidities were systemic arterial hypertension (61.1%) and type II diabetes mellitus (14.5%). 27.8% had atrial fibrillation, 15.4% and 9.4% had a history of AMI and CVA, respectively. 62% were classified as NYHA II. 90.2% implanted an ICD for secondary prophylaxis. 76.5% implanted a bicameral ICD. 13.7% had a history of arrhythmic syncope. 40.6% had episodes of unstable ventricular tachycardia (VT). 20.1% suffered cardiorespiratory arrest due to ventricular fibrillation or VT. 85, 8% did not present therapies applied by the ICD, in 13.8% appropriate therapies were applied; 0.4% took inappropriate therapies. 62.7% had high mortality by the Rassi Score. The average Maggic score was 13 points for 1 year and 29 points for 3 years. There was death in 19.7%. Conclusion: Most patients who underwent ICD implantation were for secondary prevention, but there is room for primary prevention. This pathology continues to add high morbidity and cost to its treatment (like ICD), and it is important to act at all levels of care to minimize deaths from CD. 112179 Modality: E-Poster Scientific Initiation - Non-case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Mortality in Patients with Cardiometabolic Disease During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis GABRIELLA DE SOUSA CARBALLOSA GONZALEZ1, Elisabeth Uchoa de Melo1, Erika Thienne Lopes da Silva1, Luciana Andrade Tavares1, Jose Kaellyson Barbosa dos Santos Oliveira1, Carolline Araujo1 (1) Faculdade de Medicina de Olinda The COVID-19 pandemic, responsible for the biggest health crisis today, has caused more than 6 million deaths worldwide, constituting a serious public health problem. Cardiovascular diseases, such as hypertension and dyslipidemia, associated with diabetes mellitus and obesity, characterizing the metabolic syndrome, have been associated with severe forms of the disease and death. We investigated mortality in patients with SARS-COV-2 infection and its association with cardiometabolic diseases. This is a systematic review and meta-analysis following the PRISMA recommendation. Cohort, case-control and cross-sectional studies on the investigated topic were considered. The MEDLINE/EBSCO, Cochrane Library, Pubmed and SciELO databases were consulted using strategies limited to English, Spanish and Portuguese, using the descriptors available in MeSH (Medical Subject Headings) and DeCS (Health Sciencies Descriptors) as keywords. The meta-analysis involved all studies that presented a measure of association (Odds ratio, relative risk and others) in their results. Heterogeneity was assessed using Pearson's chi-square test. A p-value was adopted, at a significance level of 5%. Data analysis was performed using Stata software. From this search, 24 articles were included. The median number of people among the analyzed works was 382 (P25 = 154/P75 = 894) and involved older individuals with a mean age of 56 years (dP = 11.4), predominantly male (63.6%). Covid-19 infection was confirmed using the RT-PCR molecular test. The mortality rate in this population was 18.5%. Among the cardiometabolic comorbidities that were significantly associated with mortality (p < 0.005), hypertension was more prevalent (25%), followed by diabetes (19.9%), obesity (18.7%) and dyslipidemia (9.35%). The presence of cardiometabolic comorbidities constituted factors associated with mortality in patients with SARS-COV2 infection. Future studies are needed to accurately determine the pathogenic mechanism involving these patients, especially hypertensive, diabetic and obese men, and the development of severe forms of COVID-19 infection. 112194 Modality: E-Poster Scientific Initiation - Non-case Report Category: CARDIOVASCULAR SURGERY Post Anesthesia Recovery After Preemptive Analgesia with Pregabalin on Cardiac Surgery: Randomized Controlled Trial - First Partial Analysis of the Pregaba-Heart Study ANA BEATRIZ VENANCIO DE PAULA BEZERRA1, Fabio Antonio Serra de Lima Junior1, David Cesarino de Sousa1, Renan Furtado de Almeida Mendes1, Raphael Patrik Borges da Costa1, Ana Gabriela Venancio de Paula Bezerra2, Joao Bosco Ferreira Gadelha3, Tiago Lucena de Brito Pereira3, Isaac Newton Guimaraes Andrade1, Andre Telis de Vilela Araujo1 (1) Universidade Federal da Paraiba; (2) Faculdade de Medicina Nova Esperanca; (3) Clinica Dom Rodrigo Introduction: Pain is one of the main morbidity factors associated with heart surgery, affecting about 50% of patients. Sternotomy can cause intense pain in the postoperative period, most commonly in the first 7 days, and can lead to significant short and long term consequences. Among the complications we can mention postoperative delirium, poor prognosis, increased length of stay in hospital and in the intensive care unit or in the post-anesthesia recovery unit, increased treatment costs and increased mortality. Few controlled and randomized clinical trials have addressed the efficacy of pregabalin administration in the perioperative period for pain control or recovery after surgery, obtaining variable results. Objectives: This study aims to evaluate the partial results if the preemptive use of pregabalin reduces the perception of pain in the patient undergoing heart surgery in the first 72 hours. Results: 23 patients submitted to cardiac surgery were randomized into two groups: 11 of them used preemptively 150 mg pregabalin starting 1 hour before surgery until the 3deg postoperative day, the other 12 used a placebo for the same period. After extubation they were evaluated in 4 moments for the visual analog scale (VAS) and clinical parameters, at the 2deg postoperative day the Qor-40 was applied. After analisis 70% were men, 78,2% had elevated blood-pressure, 39,1% had coronary arterial disease and 30,4% were diabetic. In relation to the clinical parameters studied, we verified that none showed statistically relevant differences between the use of pregabalin or placebo, but the pCO2 was the only one that was able to show a certain tendency that the pregabalin group accumulated less CO2 in the postoperative period (p = 0,074), which could mean a better thoracic expansion and therefore, less pain. The intervention group presented a mean QoR-40 of 180,17 + 17,88, while the control, 183,80 + 9,17 (p = 0,692). Revealing a non statistically significant better post-anesthesia recovery in the control group, which may be explained by an attrition bias while questioning, aimed to be ratified after team training in the remainder of this research. Conclusion: This partial analysis suggests that there may be a difference in the preemptive use of pregabalin, but it may be better verified in a bigger sample of patients. 112195 Modality: E-Poster Scientific Initiation - Non-case Report Category: EPIDEMIOLOGY AND HEALTH POLICIES/GLOBAL HEALTH The Prevalence of Death Resulting from the Specific Hypertensive Disease of Pregnancy (DHGE) in the Last Decade in Sus YURI MAGALHAES FERNANDES1, Barbara Bernardes Magalhaes1, Maria Ines Alves Brasil1, Rafaela Frota Malheiro2 (1) Universidade Estadual do Sudoeste da Bahia - Campus de Vitoria da Conquista (Bahia); (2) Faculdade Santo Agostinho - Campus Vitoria da Conquista (Bahia) Introduction: The gestational hypertensive syndrome (defined as systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg between 20 weeks of gestation and eight weeks postpartum) as a quite prevalent condition in the Brazilian population, affecting about 10% of pregnant women in the country. Furthermore, data from the Ministry of Health shows that maternal mortality in the country related to Pregnancy-Specific Hypertensive Disease (DHGE) amounts to about 35% of all maternal deaths while perinatal mortality reaches about 150 for every 1000 deliveries performed. For this, it is necessary to know the prevalence of deaths and hospitalizations related to the pregnancy-specific hypertensive disease (DHGE) in the last decade (2011-2020) in the unified health system (SUS), in order to know a little more about these comorbidities that affects many women during their pregnancy. Objectives: To analyze the prevalence of deaths and hospitalizations due to pregnancy-specific hypertensive disease in Brazil in the last decade (2011-2020) in the single health system (SUS). Methods: This is a retrospective cross-sectional study of secondary data made available by the Department of Informatics of the SUS (DATASUS) about mortality and hospitalization for pregnancy-specific hypertensive disease (DHGE) In Brazil in the period of years 2011 to 2020. Results: During this period (2011 to 2020) there were 1198 deaths across the country from pregnancy-specific hypertensive disease. The most recent data show the northeast and southeast regions with the largest number of deaths (420 and 421, respectively). It is worth mentioning the increase in the number of cases in 2011 (116) compared to 2020 (146) and the upward trend in the 2 previous years analyzed (2019, 2018), with, respectively, 118 and 112 deaths. Conclusions: The analysis of the data collected and the epidemiological knowledge about DHGE that the rate of women who still die as a result of this pathology is still high in our country. However, the most recent rates (2020 and 2019) show a great increase in relation to the previous years analyzed, leading to speculations about interrupted care or little assistance in this period, which coincides with the COVID-19 pandemic. In this sense, the analysis of these data is an important tool for understanding the national reality about care and deaths from the DHGE, as well as stimulates intervention formulation to reduce mortality in these patients. 112208 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Pulse Oximetry, Echocardiography, and Active Search for Patients: Screening for Congenital Heart Disease in the State of Paraiba LIVIA FARIAS DE HOLANDA FURTADO1, Joao Victor Bezerra Ramos1, Patricia Oliveira Lima de Macedo1, Ingrid Gabriele de Souza1, Maria Gabriela Medeiros Cunha de Araujo1, Dionarte Dantas Araujo3, Lara Andrade Dantas3, Fabricio Leite Pereira2, Claudio Teixeira Regis4, Juliana Sousa Soares de Araujo1 (1) UFPB - Universidade Federal da Paraiba; (2) Hospital Metropolitano Dom Jose Maria Pires; (3) Rede Cuidar; (4) Complexo Pediatrico Arlinda Marques Introduction: The Rede Cuidar is a health care strategy developed in Paraiba since 2018 that has as one of its lines to ensure the therapeutic care and follow-up of children with congenital heart disease in the state. The network is a primary strategy for the early identification, correct care, and follow-up of this population in the state. For this it uses three strategies: pulse oximetry test, screening echocardiogram, and active search through the caravan in 13 cities in the state, for early identification of congenital heart disease and thus reducing mortality. Objective: To describe the incidence of cardiac alterations through pulse oximetry, echocardiogram and active search of patients in Paraiba. Method: This is a retrospective epidemiological study, of observational nature, with patients screened by the Rede Cuidar between the years 2020 and 2021 through pulse oximetry, echocardiogram and active search of patients in Paraiba. Results: Over one year (November/2020 to October/2021), in 18 hospitals and maternity hospitals in Paraiba, 34978 pulse oximetries were performed, identifying 150 patients with indication for echocardiogram, which represents an incidence of 4.2 for every 1000 live births. Of those, 67 were female (44.7%), 82 (54.7%) male, and 1 (0.6%) intersex. Still, 110 (73.3%) were adequate, 19 (12.7%) large and 12 (8%) small for gestational age, 9 missing information. Throughout 2021, 379 echocardiograms were performed, of which 253 (66.7%) were abnormal, 4 (1.1%) had an inconclusive report, and 122 (32.2%) were normal. In addition, by May 2020, 596 heart patients were followed in the 13 Heart Rooms, of these 12.6% had complex type heart disease and 10.4% had obstructive type heart disease. Conclusions: One realizes, then, the importance of the strategy created in the state of Paraiba for early detection of children with heart disease, not only by traditional methods, but by actively searching in areas with difficulty in accessing a specialized health service. 112217 Modality: E-Poster Scientific Initiation - Non-case Report Category: HYPERTENSION/RENAL DENERVATION Pressure Control and Safety Profile of Antihypertensive Agents in the Puerperium: A Systematic Review FABIO ANTONIO SERRA DE LIMA JUNIOR1, Ana Beatriz Venancio de Paula Bezerra1, Ana Beatriz Torres Figueiredo de Lacerda1, Isaac Newton Guimaraes Andrade1, Andre Telis de Vilela Araujo1 (1) Universidade Federal da Paraiba Introduction: In puerperal women who had gestational hypertension, there is uncertainty regarding the choice of maintaining methyldopa or replacing it with other drugs. Objectives: This review seeks to evaluate the efficacy of different antihypertensive agents tested during the puerperium on pressure control and their safety. Methodology: MEDLINE, Embase, LILACS, Web of Science, CENTRAL and ClinicalTrials were searched for articles with terms associated with postpartum period and hypertension, eclampsia or pre-eclampsia. Randomized clinical trials that evaluated puerperal women who used antihypertensive agents during the puerperium and had their blood pressure monitored during the period were included. The primary endpoint was blood pressure control, and the secondary endpoints were incidence of hypertensive spikes and medication-associated adverse events. Results: Initially, 2470 studies were found, which were filtered by title and abstract and full text. After screening by the PRISMA method, 11 studies were included. In patients with severe preeclampsia, the most studied antihypertensive was nifedipine, which showed benefits in mean arterial pressure control and renal perfusion compared to placebo, was similar to methyldopa in duration of treatment and in need for other agents, but inferior to diltiazem and labetalol in both effectiveness and hypertensive crisis profile. Furosemide monotherapy may reduce the risk of postpartum hypertension and its faster resolution in puerperae who had non-severe gestational hypertension, while in those who had severe preeclampsia, its association with nifedipine may reduce the need for other doses of antihypertensive agents. Protocols with different durations of magnesium sulfate in the postpartum period have been evaluated, and maintaining it for 6 hours may be as effective as 24 hours, but reducing the time for bladder catheterization, the beginning of ambulation, and contact with the newborn. Clonidine and captopril had similar efficacy and safety in puerperae who had severe preeclampsia. Labetalol and nifedipine are equally effective, although the former is associated with fewer hypertensive peaks. Studies comparing methyldopa to captopril and magnesium sulfate are ongoing. Conclusion: Antihypertensives in the puerperium of gestational hypertension should be chosen according to the patient's clinical pattern, service availability, and desired profile of pressure control and side effects. 112219 Modality: E-Poster Scientific Initiation - Non-case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Analysis of the Active Search for Children with Congenital Heart Disease in the State of Paraiba in the Year 2021 MARIA GABRIELA MEDEIROS CUNHA DE ARAUJO1, Joao Victor Bezerra Ramos1, Ana Quezia Bezerra de Holanda Sousa1, Julia de Melo Nunes1, Lucas Emmanuel Freitas Mendes1, Pedro Nascimento Araujo Brito1, Patricia Oliveira Lima de Macedo1, Dionarte Dantas Araujo2, Lara Andrade Dantas2, Fabricio Leite Pereira3, Juliana Sousa Soares de Araujo2 (1) Universidade Federal da Paraiba; (2) REDE CUIDAR; (3) Hospital Metropolitano Dom Jose Rodrigues Introduction: In Brazil, 28.9 thousand children are born with congenital heart disease per year (1% of the total births). Of these, about 80% (23.8 thousand) need heart surgery, and half need surgery in the first year of life. In the context of the state of Paraiba, until 2010, there was no qualified team in the area of cardiopediatrics. Knowing this, pediatric cardiology network of services was created to work in heart disease screening programs, in order to reduce late diagnosis. To this end, the Caravan of the Caring Network is held annually, a screening program held in conjunction with the Secretary of Health of the State, which actively searches for children with heart diseases in 13 cities in the state, and refers these patients for specialized monitoring. Objective: To analyze the active search for children with congenital heart disease in the state of Paraiba in the year 2021. Methods: This is a retrospective descriptive epidemiological study referring to the records obtained by the Caravan in the year 2021. Between November and December 2021, the action traveled through the cities of Paraiba: Monteiro; Princesa Isabel; Itaporanga; Cajazeiras; Sousa; Catole do Rocha; Pombal; Patos; Queimadas; Picui; Guarabira; Mamanguape; Itabaiana. In these records, information about the echocardiogram performed on patients and the diagnosis defined by professionals were observed, in order to allow the categorizations: shunt heart disease; complex heart disease; obstructive heart disease; acquired heart disease, and arrhythmias. Results: In 2021, the total number of visits was 6291. About 92 children (1.4%) were diagnosed with some heart disease. Analyzing the diagnosis of those children, 56 (60.86%) have shunt heart disease, 17 (18.47%) have obstructive heart disease, 8 (8.69%) have acquired heart disease, 6 (6.52%) have complex heart disease and 5 (5.43%) arrhythmia. Conclusion: Therefore, the relevance of the Caravan of the Caring Network as a mechanism for the detection and diagnosis of congenital heart diseases in Paraiba was evidenced, being important for the epidemiological monitoring of the State and for ensuring early care for children with heart disease. From this perspective, a higher incidence of shunt-type heart diseases was observed in the 2021 cut-off, included in the study, representing about 60% of the diagnoses performed. 107873 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Pericarditis and Pericardial Effusion Secondary to Methotrexate Treatment: The First Case Report in Brazil of this Rare Side Effect MONIREH ZIMMERMANN RAMEZANALI1, Amanda Cristina dos Santos1, Gabrielle Purnhagen1, Natasha Silva Constancio2, Caroline de Oliveira Fischer Bacca1 (1) UNIDAVI - Centro Universitario para o Desenvolvimento do Alto Vale do Itajai; (2) Hospital Regional Alto Vale Introduction: Methotrexate (MTX) is a folic acid analogue that inhibits DNA synthesis by causing an acute intracellular deficiency of folate coenzymes. It is a pillar in the treatment of various immune-mediated diseases. Among the side effects of the MTX therapy, mucositis and hematological symptoms are common. Besides, serositis is also a major adverse effect, presenting as pneumonia and pleural effusion. Pericarditis and pericardial effusion (PE) are uncommon ones. We present the first clinical case in Brazil of MTX-induced pericarditis with PE. Case Report: 67-year-old man, with systemic atherosclerosis, started a dermatologic treatment for cutaneous psoriasis with MTX 15 mg/week. After 30 days, he complained of chest pain radiating to the right shoulder, dyspnea and hypotension. Echocardiography (ECHO) showed a moderate PE (14 millimeters), without cardiac tamponade signals. Computerized tomography revealed PE around the cardiac area, with no evidence of lynphonodes, neoplastic lesions nor infections, including tuberculosis. During hospitalization, PE was aspirated and a pericardial biopsy was made. The fluid did not reveal any abnormalities and biopsy showed a chronic inflammatory infiltrate. All the laboratory tests for rheumatoid diseases were within normal limits. The suspension of MTX therapy and use of Prednisone 40 mg daily produced improvement in symptoms within 14 days and follow-up ECHO showed complete resolution of the PE. Conclusion: Although extremely rare, pericarditis and PE might be consequences of MTX treatment. For the right diagnosis, a careful analysis should be undertaken to discontinue the drug therapy. The use of ECHO provides important information on the severity of the clinical condition. The patient was treated with MTX withdrawal and steroid therapy. 108354 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR IMAGING Renovascular Hypertension Associated with an Anomalous Intrathoracic Originated Renal Artery LARISSA ARAUJO DE LUCENA1, Felipe Leite Guedes2, Fabiano Cesar de Medeiros Junior1, Marcio Vilar de Freitas2, Rodrigo Azevedo de Oliveira1 (1) Universidade Federal do Rio Grande do Norte; (2) Hospital Universitario Onofre Lopes Renovascular disease (RVD) is responsible for 5.8% of secondary hypertension cases in young adults, caused mainly by obstructive lesions due to either atherosclerotic renal artery stenosis or fibromuscular dysplasia. Although the renal arteries' supradiaphragmatic origin is exceedingly rare, up to date, three cases of secondary hypertension due to single ectopic renal arteries originating from the thoracic aorta have been reported in patients with customarily positioned kidneys. Herein we describe a case of a 21-year-old man with resistant hypertension whose investigation showed an ectopic right renal artery originated from the internal thoracic artery. Although both renal arteries were free of obstructive lesions, the right one was very long and tortuous, causing kidney hypoperfusion. A bypass surgery between the right renal artery and the aorta was performed uneventfully, leading to better blood press control. To the best of our knowledge, there are no previous reports of secondary hypertension due to the renal artery arising from the internal thoracic artery. 108454 Modality: E-Poster Scientific Initiation - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Unusual Cases of Remote Monitoring of Implantable Defibrillators During the COVID-19 Pandemic DAVI SALES PEREIRA GONDIM3, Maria Eduarda Quidute Arrais Rocha3, Rodrigo Carvalho Paiva2, Marcela Albuquerque de Holanda2, Eduardo Arrais Rocha4 (1) Universidade Federal do Ceara-UFC; (2) Universidade Unichristus; (3) Universidade de Fortaleza-UNIFOR; (4) Centro de Arritmia do Ceara-CACE Introduction: Implantable cardiac defibrillators (ICDs) represent the most effective therapy in the treatment of severe ventricular arrhythmias. Routine follow-up with periodic scheduled office visits may not be sufficient due to the complexity of the pathologies. The COVID-19 pandemic determined more limitations in this follow-up. In this work, we report a series of cases in which remote monitoring (RM) of ICDs were of great importance in treatment. Case 1: Male patient, 65 years old, with ischemic cardiomyopathy, sustained ventricular tachycardia (SVT), with ICD implantation after reversed cardiac arrest. After 7 years, changes in the impedance of the shock electrode were detected, information transmitted remotely, requiring reprogramming in the shock vector. After 6 months, informations of changes in impedance of stimulation was received by e-mail as a red alert. Implantation of a new electrode was necessary. During the follow-up, he presented several SVTs and atrial fibrillation (AF), needing pharmacological adjustment and just one office visit for reprogramming. Case 2: Female patient, 91 years old, with ICD with multisite pacemaker due to dilated cardiomyopathy. During acupuncture, there was an ICD shock. The professional had inadvertently used electro-acupuncture. Due to portable RM, the information was transmitted to the physician, who detected an inappropriate therapy and advised the professional not to use electrical stimulation during acupuncture. Case 3: Female patient, 72 years old, with ischemic and valvar cardiomyopathy, hospitalized with SVT, when was implanted an ICD. After starting antiarrhythmics drugs, no new arrhythmias occurred in the short term. After months, she presented with several SVTs, some with high rate, reversed with anti-tachycardia pacing (ATP) and others SVTs with low rates, outside the therapy zones. AF was also detected, inappropriately recognized by the ICD as SVT and treated with inappropriate ATP therapies. Therapeutic adjustments were made and on 2 occasions there was a need for immediate reprogramming of the ICD. Discussion and Conclusion: RM of patients with ICD during the COVID-19 pandemic allowed therapeutic optimization, reduction of scheduled office visits, hospitalizations and inappropriate shocks, with an improvement in the treatment and in the quality of life. 108936 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Surgical Excision of a Large Left Ventricular Aneurysm Secondary to Chagas Cardiomyopathy Leading to Significant Clinical and Morphofunctional Improvement MIKE VINICIUS CANTO DE ANDRADE1, Natalia Barreira Silva1, Rodrigo Penha de Almeida1, Paulo Cesar Santos1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia Introduction: Left ventricular aneurysm (LVA) can be defined as a thin and dilated portion of the left ventricle (LV) due to the predominance of fibrosis and scar area. This phenomenon generates contractile disorders and, consequently, akinetic or dyskinetic ventricular segments observed during systole. They may develop after myocardial infarctions and secondary to some cardiomyopathies, such as chronic Chagas cardiomyopathy. Case Description: Female patient, 61 years old, with Chagas cardiomyopathy and heart failure (HF) functional class III (NYHA) with low tolerance to drug therapy optimization due to arterial hypotension. A transthoracic echocardiogram and cardiac catheterization were performed. The exams identified significant left ventricular dysfunction with an image of a large aneurysm associated with a thrombus at the LV apex. Pointing out the refractoriness to clinical treatment, along with complex ventricular arrhythmias on Holter and the presence of a well-defined base, it was decided to perform an LV aneurysmectomy. A significant improvement was observed in the patient's clinical state in the subsequent months. Currently, 2 years after the surgical treatment, he is in functional class I (NYHA), using Warfarin 5 mg/day, Enalapril 10 mg/day, Carvedilol 25 mg/day and Spironolactone 25 mg/day. There was a significant reduction in the size of the left ventricular cavity and a significant improvement in ventricular function (currently with normal LVEF). Not only post-surgical morphofunctional data from echocardiograms and holter will be presented, but also preoperative ventriculography and postoperative magnetic resonance imaging. Conclusion: The treatment of patients with LV aneurysms is eminently clinical, through the optimization of drug therapy for HF. However, the surgical indication of aneurysmectomy should be considered for cases that develop refractory HF, angina, complex ventricular arrhythmia and systemic embolization of intraventricular thrombi. The reported case shows that the performance of aneurysmectomy, with preservation of viable myocardium in the basal and middle portions of the LV, is capable of significantly reducing the ventricular cavity and promoting a significant improvement in the global contractile function of the LV in selected cases. Surgical treatment can also provide an important improvement in the patient's clinical condition. 108550 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Pulmonary Artery Sling - Rare Diagnosis in a Wheezing Baby BERNARDO MUSSI SOARES1, Andressa Mussi Soares2, Renata de Backer Pacifico2, Resi Apolinario2, Paulo Jose Ferreira Soares2 (1) Fundacao Tecnico Educacional Souza Marques - FTESM; (2) Hospital Evangelico de Cachoeiro de Itapemirim - HECI Pulmonary artery sling - rare diagnosis in a wheezing baby. Introduction: Pulmonary artery (PA) sling is a rare congenital vascular disease (59 cases per million children) in which the left pulmonary artery (LPA) derives from the right pulmonary artery (RPA), forming a ring that passes anteriorly to the esophagus and posteriorly to the trachea, which may compress mediastinal structures and cause severe upper airway symptoms in children. Case Description: 2 years old male child, with respiratory distress at birth, evolved with frequent wheezing and tachydyspnea, without improvement. He presented several hospitalizations for respiratory symptoms, being diagnosed with allergy to cow's milk protein. After evaluation by the immunoallergy, he was referred for echocardiographic evaluation. The echocardiogram (Echo) detected the APE emerging from the posterior wall of the RPA that originates from the pulmonary trunk and has a usual course, and the diagnosis of AP sling was made. Therefore, CT angiography of the chest was performed to better evaluate possible compressions in the trachea and esophagus. APE emerging from the dorsal surface of the RPA was detected, passing inferiorly to the origin of the upper lobar bronchus that exits directly from the trachea and over the right main bronchus, forming the vascular ring that causes a moderate degree of stenosis of the distal trachea. In addition, the APD presents an anatomical variation with anomalous segmentation at the hilum, where it trifurcates forming three main arterial trunks. This data is especially important at the time of the surgical approach to avoid incidental complications. CT angiography was performed with reconstruction focused on the air phase, allowing an excellent assessment of tracheal stenosis and thoracic esophageal distention. The child has just been diagnosed and will undergo surgery. Conclusions: Due to the non-specific symptoms, the clinical diagnosis can be difficult and delayed, compromising the general condition and in some cases leading to death in the first months of life. Echo performed in detail is a robust tool for diagnosing PA sling. The other exams offer a better assessment of the relationships with neighboring structures. With an early diagnosis and surgical correction, the prognosis is generally good, but the anatomy of the structures must be very well evaluated because the risk of death during surgery increases when there is significant bronchial or tracheal stenosis. 108571 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Importance of Cerebral Oximetry Monitoring in Cardiac Surgery with Cardiopulmonary Bypass: Case Report RODRIGO BATISTA WARPECHOWSKI1, Emmanuela Flavia Alves Pinto2, Fabiana Rodrigues Philippsen2, Paulo Warpechowski2, Tiago Luz Leiria1 (1) Instituto de Cardiologia do Rio Grande do Sul; (2) Sociedade de Anestesiologia (SANE) In cardiopulmonary bypass (CPB) surgeries, adverse events such as desaturation, hypoflow, hypoxia and brain injury may occur. Such situations may lead to complications such as cognitive decline (CO), observed in up to 50% of the patients. Herein, we present a case of hypoxia during cardiac surgery with CPB identified using the INVOSTM 5100 C Cerebral/Somatic Oximeter. Male patient, 77 years old, 80 kg, hypertensive, with root and ascending aortic aneurysm and aortic valve insufficiency. Scheduled aneurysm repair and valve replacement. No previous neurological deficits. Regional saturation (INVOSTM) and anesthetic depth (Bispectral Index-BIS) monitors were installed. Regional brain O2 saturation (rSO2) was between 65-80 and BIS between 30-60 throughout the process. At thirty minutes of CPB, there was an abrupt drop in rSO2 (Image 1), reaching critical values <40, a drop in mean arterial pressure and a BIS reduction, with high suppression rates. Arterial blood gases revealed severe hypoxemia (PO2 of 40 mmHg and SO2 of 62%). A failure in the CPB gas mixer was identified by the perfusionist and it was replaced. Subsequently, rSO2 returns to values >55. The CPB time was 138 min, and aortic aneurysm repair was performed using the Bentall de Bono procedure. The patient showed no neurological damage and progressed satisfactorily, being discharged from the ICU after 3 days and discharged from the hospital 12 days after surgery. Studies such as those by Murkin et al and Slater et al, which evaluated the effectiveness of rSO2 monitoring by INVOSTM, demonstrate that intraoperative cerebral O2 desaturation is significantly associated with an increased risk of CD and prolonged hospital stay after CPB, and its treatment was associated with a shorter length of stay in the ICU and a significantly reduced incidence of morbidity and mortality. Despite performing preventive maintenance procedures, equipment failure may occur. Thus, it is imperative that the anesthesiologist is aware and uses all available monitoring means to recognize possible failures and so that management can be carried out in the best way as possible. 108581 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Congenital Heart Disease and Its Association with the Fetal Valproate Syndrome ISADORA BUELONI GHIORZI1, Adriano Louro Moreira1, Juliana Bergmann1, Mateus dos Santos Taiarol1, Marina da Rocha Besson1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre Introduction: Valproic acid is a medication frequently used in the treatment of epilepsy, and, among anticonvulsants, it has the highest incidence of major malformations. Our aim was to report a patient with fetal valproate syndrome (FVS) presenting congenital heart disease. Case Description: The patient was the third child of a mother diagnosed with epilepsy. She used valproic acid (up to the third month) and phenobarbital (from the third month onwards) during pregnancy. She reported episodes of frequent seizures until the end of the third month of pregnancy. The female child was born by vaginal delivery, premature at 35 weeks, weighing 2450 grams and with Apgar scores of 8 at first minute and 9 at fifth minute. She had heart failure after birth. Echocardiography identified perimembranous ventricular septal defect (VSD) with a wide outflow tract, mild peripheral pulmonary stenosis, and left superior vena cava persistence draining into the coronary sinus. The evaluation also showed growth retardation, keeled skull, epicanthal folds, bilateral tear duct obstruction, well-marked infraorbital crease, anteverted nostrils, long philtrum, thin upper lip, retroverted and low-set ears, and accessory nipples to the right. Head computed tomography confirmed the diagnosis of trigonocephaly. The karyotype was normal. The child underwent surgery to correct the VSD at 8 months of age. Conclusions: The findings presented by the patient were compatible with the diagnosis of FVS. Congenital heart defects may be part of the picture and they have been described in about 25% of patients. The VSDs were less common malformations. 108591 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY The Tilt Test in Munchhausen Syndrome MARIA EDUARDA QUIDUTE ARRAIS ROCHA1, Pedro Sales Pereira Gondim3, Arthur Holanda Dantas3, Marcela Albuquerque de Holanda3, Camila Pinto Cavalcante Mina2 (1) Universidade de Fortaleza (Unifor); (2) Universidade Federal do Ceara (UFC); (3) Centro Universitario Christus (UNICHRISTUS) The Tilt Test in Munchhausen Syndrome Introduction. The Tilt Test (TT) is a complementary method widely used to investigate the susceptibility to vasovagal phenomena or late orthostatic hypotension. Reproduction of clinical symptoms is essential to the true positivity of the test and its good accuracy. Patients may present with several symptoms during the test, without concomitant hemodynamic changes, called psychogenic response. We described a remarkable case of a patient with a suspected diagnosis of Munchhausen Syndrome, a more severe form of factitious disorder self-imposed, confirmed during the TT. Case: Female patient, 22 years old, with a history of more than ten years of multiple symptoms of loss of consciousness, intensification in recent years, descriptions and videos showing tonic movements, with deviation of looking up, pallor, falls, palpitations, causing a worsening in her quality of life. She had a history of childhood sexual abuse, dependence on the use of morphine and psychotropic drugs for the treatment of fibromyalgia, herniated disk and depression. There were several hospitalizations, with suspected diagnoses of pheochromocytoma, hyperthyroidism, adrenal insufficiency, autoimmune diseases and dysautonomia, when she was referred to syncope unit for investigation. There was a hypothesis of her psychiatrist of the syndrome of post traumatic disorder. Laboratory tests showed nonspecific findings. The cardiologic tests: sinus tachycardia 120-151 bpm, even when lying down; normal 24-hour Holter with RR variability showing preserved autonomic balance. Neurologic tests were normal. In 2020, she underwent TT with a report of pseudo syncope. In 2021, during a recorded TT, there was full reproduction of the symptoms, without any correlation with hemodynamic changes. The diagnosis was made according to the criteria of the manual diagnostic for mental disorders (DSM-5), and she was forwarded to the psychiatrist. In the evolution, the patient no longer returned for revaluation, a situation described in this syndrome after confirmation of the diagnosis, remaining meanwhile with evaluations by other professionals. Discussion and Conclusion: This work highlights the importance of knowledge of Munchhausen Syndrome due to the wealth and multiple symptoms presented and the role of the Tilt Test in excluding other etiologies, since the diagnosis is rarely done by the psychiatrist, but mainly by the specialist. 109134 Modality: E-Poster Scientific Initiation - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Acute Decompensation of Heart Failure by COVID-19 with Need for Heart Transplant: A Case Report CAROLINA TISOTT BURTET1, Amanda Hillesheim Schuck1, Maria Constanza Ce Erig1, Rafaella Magni Berthier1, Olga Sergueevna Tairova1 (1) Universidade de Caxias do Sul (UCS) Introduction: Coronavirus disease (COVID-19) is an infectious disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with previously established comorbidities, such as heart failure, are at particularly high risk of morbidity and mortality from this infection - they generally have a worse prognosis and a mortality rate of more than 10%. Studies suggest that viral infections can exacerbate a preexisting cardiac insufficiency, with multiple mechanisms responsible for triggering and aggravating this process. Case Description: Female patient, 34 years old, without comorbidities. History of mild blood pressure increase and left ventricular enlargement since 2015. Progression of loss of ejection fraction (EF) up to 20% after COVID-19 infection in December 2020. Evolved with worsening of the general condition, acute heart failure and need for sequential dialysis. After the condition, the patient became a candidate to receive a heart transplant, which was performed in February 2021, with good postoperative clinical evolution. Complementary tests after transplant: Electrocardiogram with regular rhythm, HR 95, without alterations; Echocardiogram with improvement in EF (69%), anomalous movement of the interventricular septum and left atrial enlargement. Stress Test: Distance covered 0.86 km; Duration 11 minutes; maximum HR 129; Max Vo2 15.44; Maximum power: 29.9 W; NYHA III functional group; Also showing a very low cardiorespiratory fitness (AHA). The patient has been followed up on a weekly basis for physical and cardiopulmonary rehabilitation at the Sports Medicine outpatient clinic, with good evolution. Conclusion: Acute infections result in an inflammatory cascade, leading to a severe inflammatory storm that can exaggerate the initial injury. Furthermore, it is already documented that increased metabolic demand can lead to cardiac depression and new-onset heart failure or acute decompensation of chronic cardiac insufficiency. The case above describes a severe acute decompensation in a young patient, without associated comorbidities with the need for immediate heart transplantation. Thus, we can conclude that it is essential to understand the interactions between heart disease and the virus to prevent unfavorable outcomes like this one and improve the management of these patients. In addition, there are yet few reports in the literature that demonstrate the need for heart transplantation after COVID-19. 108771 Modality: E-Poster Scientific Initiation - Case Report Category: HYPERTENSION/RENAL DENERVATION Renal Artery Angioplasty and Stent Implantation in Patient with Refractory Arterial Hypertension Associated to Low Back Pain and Progressive Renal Dysfunction DANIELLE CAMPOS DE ALMEIDA1, Benara Otoni de Siqueira1, Ebes Kleofas da Silva Magalhaes1, Gabriel Alves Meneses1, Joao Lucas O'Connell1 (1) Faculdade de Medicina, Universidade Federal de Uberlandia Introduction: Renal Artery Stenosis (RAS) in elderly is, in most cases, a consequence of a progressive atherosclerosis, that may be associated with other blood vessels atherosclerosis. The most common symptoms are related to tough control of blood pressure (an important cause of secondary hypertension) and renal insufficiency. It's described a patient's case with multiple comorbidities and systemic atherosclerosis, evolving with refractory arterial hypertension, low back pain and progressive renal disease, even as relevant right renal artery stenosis. Case Description: 75-years-old woman, smoker, hipertensive and dyslipidemic, with previous transitory ischemic attack, bilateral carotid stenosis, carotid endarterectomies, acute myocardial infarction, coronary angioplasties and stents implantation, mesenteric artery angioplasty with two stent implantation. Presenting for six months with worsening of blood pressure control (maintaining levels higher than 170 mmHg), right low back colic-like pain episodes, and recent worsening of creatinine levels (from 1,6 to 2,5 mg/dL). It was requested an abdominal aorta angiotomography (and renal arteriography later) that identified important right renal artery stenosis. The Patient was subjected to a angioplasty and successful stent implantation in the right renal artery without any complications. There was improvement of low back pain, blood pressure control and creatinine levels (returning to normal values). Performed new abdominal aorta angiotomography that detected blood vessels permeability and absence of stenosis within previously implanted prosthesis. Conclusion: Renal Artery Stenosis diagnosis can be done by renal artery doppler, renal scintigraphy and abdominal aorta angiotomography. Concerning treatment, literatura still is controversial about drug treatment and percutaneous modalities effectiveness. For some cases, as described here, interventionist approach, renal artery angioplasty and stent implantation, may be mandatory for blood pressure control, pain control, due to a renal ischemia and to avoid renal insufficiency. 108778 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Progressive Chest Pain Evolving to Pericardial Effusion and Cardiac Tamponade Due to a Cardiac Suture Needle Perforation Used in Maxillofacial Surgery Decades Before DANIELLE CAMPOS DE ALMEIDA1, Karina Baltor Cabral1, Mike Vinicius Canto de Andrade1, Paulo Cesar Santos1, Joao Lucas O'Connell1 (1) Faculdade de Medicina, Universidade Federal de Uberlandia Introduction: Cardiac perforations usually are due to stab wounds or bladed weapons, firearms or eventually due to chest trauma followed by penetration of foreign bodies inside the chest wall. Although most of cardiac perforations are life threatening, minor lacerations may evolve to tamponade and cardiac surgery can avoid death. Cardiac perforations because of sharp perforation material are rare. Even more uncommon when surgical material was used on procedures outside the chest. Case Description: A female patient of 60-years-old woman had orthognathic surgery 36 year ago and post-surgery identification of a suture needle "forgotten" on cervical region. Comes into the Emergency Room complaining about a progressive chest pain ventilator-dependent, associated with dyspnea. Physical exams evidence pericardial friction rub. Electrocardiograms and myocardial necrosis markers had no major changes. Coronary angiography showed absence of coronary obstruction. However, a suture needle was identified in the topography of the right ventricle (RV). A chest tomography was performed and revealed pericardial effusion and thickening, as well as micro-perforations of RV free wall associated with needle suture image. After two days, the patient evolved with an increase in pericardial effusion and tamponade cardiac signs, requiring emergency surgery aiming to remove the foreign body, followed by ventricule suture and pericardiocentesis. Patient is asymptomatic six months after the event. Conclusion: Cardiac perforations caused by "forgotten" foreign bodies in previous surgeries are rare. Furthermore, if associated with surgical material used in surgeries outside the chest. The needle displacement from cervical region to chest cavity was very likely provoked by shoulders and knees magnetic resonance imaging (MRI) performed four months before. The magnetic field produced by MRI equipaments is capable of shifting ferromagnetic objects first implanted, that may result in tissue injury. The fast and efficient cardiac surgery was essential to manage cardiac tamponade, foreign body removal, RV suture and to save the patient's live. 108783 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Acute Coronary Syndrome Associated with Anomalous Origin of the Right Coronary from the Left Coronary Sinus and Interarterial Course: A Challenging Clinical Scenario DANIELLE CAMPOS DE ALMEIDA1, Alice Mirane Malta Carrijo1, Marcela Gomes de Souza1, Gabriel Alves Meneses1, Joao Lucas O'Connell1 (1) Faculdade de Medicina, Universidade Federal de Uberlandia Introduction: Coronary Artery Anomalies (ACA) are characterized by changes on these vessels origin, course or structure. Compose a rare condition: less than 1% of general population. Within these anomalies, there are anomalous origin of coronary arteries from aorta which can have retroaortic, subpulmonary, pre-pulmonary and interarterial courses. At large, these abnormalities remains asymptomatic until adult age and are incidental findings on complementary exams or necropsy. Yet, it can cause angina, syncope, ischemia, arrhythmia or sudden death, especially in young athletes. Case Description: 56-years-old men, hypertensive, family history of coronary disease, dyslipidemic, pre-diabetic, sedentary and obese. Was admitted in the hospital for evaluation of mild unstable angina. Electrocardiogram (ECG): Sinus rhythm and left ventricular overload signs. There wasn't any increase on cardiac enzymes. Coronary angiography highlighted the origin of the right coronary from the left coronary sinus, slit ostium and moderate ostial stenosis (for probable extrinsic compression). Left coronary without stenosis. Left ventricules' global and segmental systolic function were preserved. Coronary artery angiotomography confirmed inappropriate RCA origin from left valsalva sinus, interarterial course (between aorta and pulmonary artery) and proximal moderate luminal reduction ("slit-like orifice" course). The possibility of surgical treatment has been considered, however it was opted for myocardial scintigraphy which showed normal myocardial perfusion. The conduct taken was drug therapy maintenance. The Patient remains asymptomatic even after two years passed from initial diagnosis. Conclusions: Although anomaly's interarterial course is associated to higher incidence of sudden death, especially after vigorous exercises, low physical efforts diaries, associated with absence of detectable ischemia on appropriate exam, reduce risk for fatal events, as well corroborates the therapeutic option chosen on this case. Moreover, the absence of angina symptoms after drug treatment also reinforces the initial non-interventionist option for the case in discussion. 108789 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Acute Myocardial Infarction in a Young Man Caused by Spiral Spontaneous Coronary-Artery Dissection of the Left Coronary Trunk, Anterior Descending and Circumflex: A Surprising Clinical and Angiographic Scenario ISABELA MARTINS RODRIGUES1, Joaquim Adelio de Oliveira Neto1, Ana Julia Carvalho Paulinelli1, Gustavo Nahuel Leyes Ontivero1, Joao Lucas O'Connell1 (1) Faculdade de Medicina da Universidade Federal de Uberlandia Introduction: Spontaneous Coronary-Artery Dissection (SCAD) is defined as the rupture of the intima and media layer of an epicardial coronary-artery wall by an intramural hemorrhage and is not secondary to atherosclerotic disease, aortic dissection, or intravascular trauma. SCAD occurs primarily in women, and the predisposing factors include intense emotional stress, intense physical activities (especially isometric exercises), hormone therapy, use of corticosteroids, use of cocaine, and smoking. Case Description: A 39-year-old man, smoker, and cocaine user was referred to our hospital with intense chest pain at rest, associated with dyspnea, for more than 24 hours. He maintained mild chest discomfort at the time of admission and was hemodynamically stable. The electrocardiogram showed sinus rhythm, mild and diffuse ST-segment elevation. Coronary angiography revealed dissection in the left coronary trunk, involving the entire left anterior descending artery and the entire first left marginal branch with distal occlusion of these two vessels. Left ventriculography showed a significantly decreased global left ventricular systolic function, dyskinesia of the anterolateral wall, and akinesia of the apical and inferoapical walls. An attempt was made for coronary angioplasty in marginal branch, without success, because access to the true lumen of the vessel was not possible. Clinical treatment was performed and reassessment was scheduled with a new coronary angiography in 30 days or an emergency cardiac surgery in case of instability of the condition. The patient remained stable, and drug treatment was maintained for Coronary Artery Disease and Heart Failure. He is asymptomatic with partial recovery of ventricular function one year after the initial condition. Conclusion: SCAD is a dramatic clinical and angiographic situation that can lead to death in young individuals without risk factors for coronary artery disease. There is a current trend towards adopting a conservative strategy, especially in those patients without recurrent ischemia. When attempting angioplasty, verification of the correct positioning of the guidewire in the true vessel lumen is mandatory. Stent angioplasty has failure rates that can reach 35.0%. The case reported is a SCAD, probably due to cocaine use, with spiral dissection involving multiple vessels. Despite the severity of the lesions, the conservative approach was successful, and the patient presented a satisfactory clinical response. 108790 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Left Ventricular Pseudoaneurysm Rupture: A Tragedy that Must be Avoided MIKE VINICIUS CANTO DE ANDRADE1, Leticia Guimaraes Mendonca1, Natalia Barreira Silva1, Eduardo Henrique Costa Vitor1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia Introduction: Often, even patients with a favorable evolution in the first days after an Acute Myocardial Infarction (AMI) can develop important mechanical complications. These complications can be sudden and lethal, such as, for example, left ventricular (LV) free wall rupture. Another serious mechanical complication of patients with AMI is LV pseudoaneurysm, which develops due to rupture of the left ventricular (LV) wall contained by pericardial adhesions. When not diagnosed and treated early, the pseudoaneurysm can also have a catastrophic course. Case Description: Male, 65 years old, presented with non-thrombolyzed inferolateral wall AMI. Coronary angiography, still in the hospital phase: three-vessel obstructive pattern with important and proximal stenosis in the anterior descending and circumflex arteries, in addition to total occlusion of the right coronary artery. Ventriculography showed a large extension of akinetic area in the inferior wall and "image suggestive of aneurysm in the inferior wall of the LV". He was discharged from hospital on the sixth day; he was advised to look for a cardiac surgeon to schedule coronary artery bypass graft surgery (and possible LV aneurysmectomy). Outpatient echocardiogram (performed on the tenth day after AMI) identified the presence of a pseudoaneurysm of the inferior wall of the LV. Still in the echocardiography room, the patient had a cardiorespiratory arrest in a pulseless electrical activity (PEA) rhythm, which was not reversed after cardiopulmonary resuscitation (CPR) or puncture pericardiocentesis maneuvers. A new echocardiogram during cardiac arrest confirmed an image suggestive of significant pericardial effusion with signs of cardiac tamponade, not identified in the exam performed a few minutes earlier. Conclusion: Left ventricular aneurysms and pseudoaneurysms are types of mechanical complications associated with AMI and the differential diagnosis between one situation and another is still a challenge in clinical practice. Unlike true aneurysms, false aneurysms have a high tendency to rupture and should be operated on soon after diagnosis. This report reinforces the importance of careful analysis of risk factors for the occurrence of mechanical complications after AMI and also of careful analysis of echocardiography and ventriculography images that allow early treatment of this potentially fatal clinical situation when the diagnosis is not made. 108799 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Sudden and Unprecedented Mental Confusion as the Only Clinical Manifestation of Spontaneous Coronary-Artery Dissection in an Athlete ISABELA MARTINS RODRIGUES1, Rodrigo Penha de Almeida1, Dennis Miguel Lemos da Silva1, Fabiane Mian de Souza1, Joao Lucas O'Connell1 (1) Faculdade de Medicina da Universidade Federal de Uberlandia Introduction: The occurrence of concomitant association between acute coronary syndrome and stroke is rare. Although several cases have been described in the literature, we did not find any case description of a patient with concomitant cerebrovascular accident (CVA) associated with Spontaneous Coronary-Artery Dissection. Case Description: A 39-year-old man, tennis coach, and player without morbid history or classic risk factors for coronary artery disease presented to our hospital with sudden mental confusion, disorientation, and mild dysarthria, with partial reversal during the 7-day hospital stay. Magnetic Nuclear Brain Resonance showed alterations compatible with stroke. Electrocardiographic and echocardiographic alterations were seen suggestive of acute inferior wall myocardial infarction and led to the performance of coronary angiography, which revealed proximal occlusion of the right coronary artery, receiving grade II coronary collaterals left, without stenosis in other coronary arteries. Left ventriculography showed significant hypokinesia of the inferior wall with preserved global systolic function. We decided not to approach the right coronary artery at that time and the possibility of coronary dissection was considered a pathophysiological mechanism to explain the acute coronary syndrome and mobilization of the coronary thrombus to explain the consequent cerebral embolism. He returned 30 days after the initial condition and identified a recanalized right coronary artery, with subocclusive stenosis in the proximal segment and an image compatible with a long line of coronary dissection. Angioplasty of the right coronary artery was performed with successful implantation of two stents. The patient remains well and without further events two years after the initial event. Conclusion: Several pathophysiological mechanisms can explain the occurrence of simultaneous ischemia in cardiac and cerebral territories. Firstly, the same traditional risk factors act for the genesis and rupture of obstructive atherosclerotic plaques in both territories. Secondly, one can also lead the other which justifies the simultaneous manifestation of the conditions. The initial percutaneous approach to a coronary vessel suspected of having dissection can be postponed to a second moment, in case of clinical stability of the patient. In the case reported, this initial clinical management proved to be very important. 108802 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Myocardial Infarction Associated with Massive Right Coronary Aneurysm: A Challenging Case LETICIA GUIMARAES MENDONCA1, Gustavo Nahuel Leyes Ontivero1, Victor Custodio Ribeiro1, Sthephany Yamaguchi de Melo1, Joao Lucas O'Connell1 (1) Universidade Federal Uberlandia Introduction: Coronary aneurysm (CA) is defined by the presence of a vessel segmental dilatation 1,5 times larger than the adjacent segment or as the largest vessel's segment with the larger diameter of the vessel. Aneurysms incidence varies between 1,5% a 5% in adults and is more frequent in males. Also, this condition is related to Takayasu, Kawasaki arteritis, Polyarteritis Nodosa, and syphilitic, or previous exposure to trauma, dissection, angioplasty, atherectomy, and herbicides. The role of the classical risk factors in the genesis of aneurysms is controversial. Case Description: Male, 49 years, class 3 obesity, hypertensive. Appeared with Non-ST segment elevation myocardial infarction (NSTEMI) of the inferior wall. Heart catheterization showed ectasias along the entire length of the right coronary, an aneurysm (vessel maximum diameter 12 mm), and an occlusive thrombus in the middle third. The exam also showed coronary ectasia, without significant stenosis in the anterior interventricular and circumflex branches. An attempt of primary balloon transluminal coronary angioplasty was made, it was associated with intracoronary thrombolysis and venous Alteplase maintenance, obtaining TIMI II coronary flow. A coronary stent wasn't possible due to de excessive dilatation of the vessel. The patient evolved well until his hospital discharge and did not present new cardiological problems in the last 4 years. The patient took Aspirin for the first 28 days. Currently, he takes Atorvastatin (80 mg/day), Metoprolol (50 mg/day), Clopidogrel (75 mg/day), and Rivaroxaban (15 mg/day). Conclusions: The pathophysiology of CA is related to multifactorial endothelial damage, which activates inflammatory mediators and vasodilator substances that lead to degeneration of the vessel layer and progressive coronary dilatation. Percutaneous revascularization can be associated with distal thrombus embolization, no-reflow phenomenon, malposition of the stent, dissection, and flow compromise. There are no specific guidelines for the management of CA in acute coronary syndrome and there is no data in the literature about the efficacy of thrombolytic therapy in this case. Finally, this case suggests that balloon angioplasty and the use of thrombolytic, followed by the clinical treatment optimized with high doses of statin, and antiplatelet aggregation associated with anticoagulation in the long term, can be good therapeutic choices for some selected cases of NSTEMI with CA. 108805 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Silent Aortic Coarctation in Adulthood Associated with Bicuspid Aortic Valve, Aneurysm and Stanford B Aortic Dissection: A Case Report CAROLINE DA SILVA TEIXEIRA1, Lucca Ziravello Elias Coelho1, Gabriela Rodrigues de Oliveira2, Ricardo Santiago Ferreira Coelho2, Juliano Novaes Cardoso2 (1) Faculdade Santa Marcelina; (2) Hospital Santa Marcelina Coarctation of the aorta (CoA) is not only considered a narrowing of the aorta but part of a generalized arteriopathy. The incidence corresponds to 3 cases per 10.000 births. The associated lesions include a bicuspid aortic valve (BAV) in up to 85% of the cases. Patients with mild CoA may not manifest until adulthood, which can be accidentally diagnosed through clinical examinations as arterial hypertension. This case discusses a 36-year-old male who presented to the emergency department with a 1-hour history of sudden, tearing and severe (10/10 intensity) retrosternal pain radiating to his back. Initial electrocardiogram revealed first-degree AV block and left anterior superior divisional block. Blood pressure was different between the upper and lower limbs. His past medical history includes a non-investigated and non-treated asymptomatic arterial hypertension since he was seven years old. Aortic dissection was suspected and further investigation with angiotomography was realized. The image revealed an aortic coarctation after the emergence of the subclavian artery, associated with an aortic fusiform aneurysm after the stenotic region, parietal thrombus, aortic ulcer, and dissection flap. A transesophageal echocardiogram was performed, which detected a bicuspid valve with significant insufficiency. The patient was hospitalized, medicated and awaiting a surgical procedure. A medical history of re-coarctation, descending aortic aneurysms, hypertension, and recurrent procedures associated with congenital heart disease are related to higher cardiovascular morbidity. The diagnosis of CoA is the most commonly missed, being detected at the prenatal screening with less than one-third of the cases. In conclusion, early diagnosis is very important to reduce disease morbidity. 108816 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR PHARMACOLOGY Blue-Gray Syndrome: A Rare Amiodarone-Induced Dermopathy HELENA MARCON BISCHOFF1, Helena Marcon Bischoff1, Sergio Ferreira de Ferreira Filho2, Raphael Boesche Guimaraes2, Mathias Silvestre de Brida2 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (2) Instituto de Cardiologia do Rio Grande do Sul/Fundacao Universitaria de Cardiologia (IC-FUC) Introduction: Amiodarone is a widely used drug in the treatment of arrhythmias, however, its metabolites are responsible for numerous side effects. We report a rare dermopathy secondary to the chronic use of amiodarone. Case Description: Female patient, 57 years old, hypertensive and with a history of paroxysmal atrial fibrillation and mechanical mitral valve prosthesis, on chronic use of warfarin and amiodarone, sought consultation due to the appearance of bluish spots on her face and upper limbs in the last three months. She reported daily use of 400 mg of amiodarone for the last four years. Patient had lost medical follow-up, with no consultation in the last 4 years. On physical examination, areas of blue-gray hyperpigmentation were found in photoexposed areas, predominantly on the face and upper limbs. Chest X-ray and laboratory tests to evaluate other adverse effects were unremarkable. Considering the characteristic clinical findings, the hypothesis of amiodarone-induced skin disease, known as Blue-Gray Syndrome was raised. The patient was then instructed on the discontinuation of the drug, protection against sun exposure and the need for ophthalmological evaluation. After four months, she showed significant improvement in the lesions. Conclusions: Blue-Gray Syndrome is an adverse effect that occurs in 1 to 7% of patients on chronic use of amiodarone. Differential diagnosis is made with other situations that cause facial discoloration, especially with the use of chlorpromazine and tricyclic antidepressants. Treatment is based on photoprotection and drug suspension, with usual resolution of the discoloration in 6 to 12 months. In conclusion, side effects of amiodarone should be widely known to the prescriber and follow-up is necessary in order to avoid unwanted events. 108822 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Rupture of the Left Ventricle After the Acute Myocardial Infarction: A Dramatic Clinical Situation VICTOR CUSTODIO RIBEIRO1, Huggo Santana Machado1, Rodrigo Penha de Almeida1, Dennis Miguel Lemos da Silva1, Joao Lucas O'Connell1 (1) Universidade Federal Uberlandia Introduction: Complications after myocardial infarction (MI) includes mechanical, arrhythmogenic, and hemorrhagic causes. In general, it happens in the first 5 days after the MI, which justifies the orientation of keeping the patients hospitalized during this period. However, the risk of complications remains high until the 14th day. The mechanical causes are more frequently associated with MI with ST-segment elevation, being responsible for 15% of the deaths by MI. There is a higher risk associated with a larger extension of the necrosis area, the longer period of time until the myocardial reperfusion, and the treatment with fibrinolytic (when compared to primary angioplasty). Case Description: Female, 74 years, obese, smoker, family history of coronary heart disease. Presented with typical chest pain, being admitted 36 hours after the beginning of the symptoms, already asymptomatic. The electrocardiogram showed an ST-segment positive deflection in the inferolateral-dorsal wall and right ventricle (RV). The patient evolved with decompensated heart failure and improved after clinical support. The echocardiogram showed biventricular dysfunction with a left ventricular ejection fraction of around 50%, inferior akinesia, and inferolateral hypokinesia. The cineangiocoronariography indicated a multivessel obstructive pattern, and surgical treatment was chosen. On the fifth day of hospitalization, the patient presented with abdominal pain followed by a sudden loss of consciousness without pulse. Cardiopulmonary resuscitation and Marfan puncture were done, with a moderate volume of bloody secretion expelled. Unresponsive, the patient evolved to death. At necropsy, a rupture of the posterior wall of the left ventricle with hemopericardium was identified. Conclusion: The most severe mechanical complication after MI is the rupture of the left ventricle. This condition is 7 times more common than RV rupture, with an incidence of up to 10%, especially when it affects territories supplied by the anterior descending artery. The acute form, with the presence of hemopericardium, progresses fast to death. The chronic form can be asymptomatic with the formation of pseudoaneurysms. Our case reinforces the importance of effective and early revascularization treatment. The persistence of ST-segment elevation after 72 hours attests to the risk of serious complications. Pericardiocentesis is an interim measure until clinical stabilization and referral for cardiac surgery. 108828 Modality: E-Poster Scientific Initiation - Case Report Category: ATHEROSCLEROSIS/CARDIOVASCULAR RISK FACTORS/CARDIOVASCULAR PREVENTION Double Anterior Descending Artery Associated with Severe Atherosclerotic Disease Both in the Native Vessel and at the Origin of the Anomalous Anterior Descending Artery (In Bifurcation with the Right Coronary Artery) RIZIA CARLA DA SILVA LEOPOLDINO1, Karina Baltor Cabral1, Fernanda Fernandes Goncalves Ribeiro1, Caio Araujo da Cunha1, Joao Lucas O'Connell1 (1) Universidade Federal Uberlandia Introduction: Coronary artery anomalies have an incidence ranging from 0.1% to 1.4% in studies of necropsy and coronary angiography series. These anomalies are mostly benign and asymptomatic. However, they can cause symptoms when there are repercussions on coronary flow. The diagnosis of double Anterior Descending Artery (AD) occurs when identifying a short anterior descending artery that runs in the interventricular groove but does not reach the cardiac apex, and another long anterior descending artery, which has a variable proximal course and returns to the distal interventricular groove. The incidence of this type of anomaly is low: 0.017%. There is little data in the literature on the incidence of severe obstructive disease related to double AD. Case Description: A 68-year-old female patient presenting myocardial ischemia in angina investigation. Coronary angiography was submitted that identified double AD and the presence of obstructive coronary artery disease associated with both the proximal segment of the AD (originated from the left coronary trunk) and the anomalous AD ostium (bifurcation stenosis with the right coronary artery (DC), which also presented important stenosis). The patient underwent Coronary Angioplasty for both branches of AD and DC, with good clinical and angiographic evolution. Images of coronary angiography will be presented before and after angioplasty treatment. The patient progressed well clinically and is asymptomatic, 2 years after angioplasties. Conclusion: The diagnosis of double AD is given by coronary angiography or, more recently, by coronary tomography. Double AD should be suspected when there is a discrepancy between the apparent coronary distribution pattern and the motility of the ventricular walls. Dual Type IV AD is characterized by the origin of long AD in the right Valsalva sinus or right coronary artery. This anomaly is rare: 0.004% - 0.006%. Double AD can also be confused with occlusion of the middle third of AD, especially if only left coronary angiography is performed and long anomalous AD does not undergo selective catheterization. In addition, this anomaly may be associated with coronary obstructive atherosclerotic disease and the clinical aspects of the patient, angiographic complexity, and discussion among the members of the heart team should be considered in order to offer the best therapeutic proposal to patients with this pathology. 109111 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY From Acute Myocardial Infarction to Intraventricular Communication: Case Study INGRID SAGRILLO1, Julia Carvalho Brasil Malaquias1, Cezar Ladeira Macedo Junior2, Juan Dias de Lima2 (1) Faculdade de Minas - Muriae (FAMINAS - Muriae); (2) Casa de Caridade Hospital Sao Paulo (HSP - Muriae) Introduction: The intraventricular communication (IVC) is among the main mechanical complications of acute myocardial infarction (AMI), with an incidence of 0.2%, next to free-wall papillary muscle rupture, all generally associated with hemodynamic instability and high mortality. Case Report: J.H.V., a 59-year-old male, without previous comorbidities, came to the emergency room with typical chest pain for 20 hours, and electrocardiogram showed supra-ST-segment elevation in the inferior wall. He was immediately transferred to the hemodynamics department where primary angioplasty of the occlusive lesion of the right coronary artery was performed. On the third day after the onset of symptoms, the patient developed anginal pain, sweating, hypotension, and transthoracic echocardiogram showed IVC and Left Ventricular pseudoaneurysm (LVP). Thus, the patient was referred to a new hemodynamic procedure for percutaneous closure of the two IVC holes together with the LVP. Conclusion: The main symptom of AMI is sudden and constant chest pain due to reduced blood flow. Diagnosis is through the electrocardiogram, which shows a ST-segment elevation. Left ventricular pseudoaneurysm is a rare complication after AMI that results in ventricular wall rupture without cardiac tamponade. It is diagnosed by echocardiography or nuclear magnetic resonance, but most are done in the chronic phase, which often evolves asymptomatically. However, once diagnosed, it must be treated surgically. Echocardiography is also the gold standard for the diagnosis of IVC, in which it causes significant occlusions, which with advancing age may arise adjuvant diseases. The treatment of choice is surgical, usually -pericardial patch-, with low operative mortality and good long-term results. 108846 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Severe Cor Pulmonale in a Patient with Pickwick Syndrome VALENTINA BRATTI DE NADAL1, Pedro Boustany Escobar1, Isabelle Gambin Antonini1, Leonardo Mussoi1, Rafael Coimbra Ferreira Beltrame2 (1) Universidade do Vale do Rio dos Sinos (UNISINOS); (2) Hospital Dom Joao Becker Introduction: Pickwick syndrome (PS) is defined by obesity, chronic hypoventilation and hypercapnia in absence of other secondary causes. Pulmonary hypertension with cor pulmonale is one of the consequences of severe untreated forms. Although well described, PS is often underdiagnosed. The following case illustrates the history of the untreated disease and the current challenges in its diagnosis. Case Description: A 43-year-old male with grade 3 obesity, hypertension and obstructive sleep apnea syndrome with CPAP indication, was admitted due to generalized peripheral edema with spontaneous transudation through lower limbs skin, and dyspnea at rest initiated within the last 3 months. He was on continuous and multiprofissional care regarding his obesity for 8 years, being in pre-op evaluation for bariatric surgery. At admission he weighed 230 kg, oxygen saturation was 85% on room air, and cyanosis, jugular turgor, bilateral pulmonary crackles were present. Echocardiogram showed biventricular dysfunction . Abdominal tomography showed congestive hepatomegaly and splenomegaly. Managed with arterial and pulmonary vasodilators during hospitalization, CPAP and high dose diuretics, with complete improvement of congestion and 67 kg of fluid loss - discharge with 163 kg. Arterial blood gas analysis on room air after compensation showed a pCO2 of 63.3 mmHg and a pO2 of 52.6 mmHg, confirming the diagnosis of PS. Discharged with nutritional plan designed for obesity care, treatment for pulmonary hypertension and biventricular dysfunction, CPAP and home oxygen therapy. Conclusions: Obesity is a public health epidemic. The patient above received long standing medical follow-up for obesity, without ever receiving specific evaluation for PS and its consequences, resulting in extremely advanced cardiopulmonary disease. Although a well-described entity, PS is rarely remembered and treated early by health care teams. The reasons are multifactorial, ranging from negative health care team biases related to the treatment of obese patients to lack of focus on the particularities of care for this group of patients. 108892 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Acute Myocardial Infarct: Management of Coronary Events Due to use of Cocaine in Emergency Scenery ELISA ROCHA NONEMACHER2, Elisa Rocha Nonemacher2, Gabriel Almeida Krul2, Rafaela de Oliveira Leite2, Marcelo Sabedotti1 (1) Hospital Geral; (2) Fundacao Universidade de Caxias do Sul Introduction: Cocaine is one of the most used illicit drugs worldwide. Its use can lead to acute or chronic cardiovascular intoxication - among them, the Acute Coronary Syndromes (ACS), aortic dissection and rupture, arrhythmias and cardiomyopathies stand out. Its effect is related to blocking adrenergic reuptake in the synaptic cleft in addition to blocking sodium channels. The acute myocardial infarction is present in 6% of the population with recent cocaine use. Clinic History: 44-year-old woman, with a history of systemic arterial hypertension, smoker and cocaine user for 8 years. She sought emergency for medical care complaining of typical chest pain, associated with nausea, in 90 minutes of evolution. She was referred to the Coronary Intervention Unit of reference in the region, 4 hours after the onset of pain. On examination, she was with signs of hypertension and tachycardia. Electrocardiogram (ECG) with sinus tachycardia, ST elevated myocardial infarction (STEMI) in anteroseptal-lateral wall, being referred for early intervention. Coronary Coronary angiography demonstrated occlusion of the anterior descending artery. The thrombus burdens were aspirated resulting in restoration of coronary flow. Right after there was insertion of a drug-eluting stent in the affected artery, with clinical and hemodynamic improvement. Cocaine is a substance that, from a cardiological point of view, generates a cascade of events that is conducive to acute coronary syndromes, as it is a potent platelet activator, in addition to increasing heart rate and promoting vasoconstriction (mediated by alpha receptors). The blockade of sodium channels also contributes to a tendency to ventricular arrhythmias. Regarding drug therapy, it is prudent not to prescribe beta-blockers, especially in the acute phase, due to the risk of diverting all adrenergics from the synaptic cleft to alpha receptors, worsening the deleterious effects of cocaine. Conclusion: Considering that ACS are an important cardiovascular consequence of cocaine use, proper investigation and early treatment are necessary. Even though protocol treatment is the most appropriate alternative, there are some important differences in relation to conventional drug treatment that should be considered. 108893 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Intranodal Lymphangiography in the Assessment and Treatment of Chylous Pleural Effusion in an Univentricular Case Report PEDRO RAFAEL VIEIRA DE OLIVEIRA SALERNO1, Santiago Raul Arrieta2, Mario Henrique Hattori2, Willian Yoshinori Kawakami3 (1) Faculdade Pernambucana de Saude; (2) INCOR-SP; (3) Hospital das clinicas da faculdade de medicina da universidade de sao paulo Introduction: In univentricular patients, lymphatic complications, such as CPE, represent an important cause of morbidity and mortality.1 Identification of the source of the leak and management remains a challenge. ILG provides visualization of the lymphatic system and may represent a therapeutic alternative to surgical ligation of the TD2. Case Report: 10-month-old patient, 6,6 kg, born full-term, with an intrauterine diagnosis of double-inlet single ventricle with aortic atresia and hypoplasia of the aortic arch presented with irritability. Patients' medical history included stage 1 hybrid palliative surgery with 7 days of life and Norwood-Glenn, atrioseptostomy, and stent placement in the left pulmonary artery at 8 months of life. CPE on the fifth postoperative day was reported. Physical examination: cyanotic child, dyspnea, and no fever. Gasometry with a Sat02 83,8%, lactate 18 mg/dL. Chest X-ray showed bilateral pleural effusion. Tube thoracostomy (TT) was performed, pleural fluid analysis: triglycerides 515 mg/dl and cholesterol <50 mg/dl. With a high bilateral TT drainage (46,66 ml/kg) and failure of clinical management, ILG was done. Guided by ultrasound, an inguinal lymph node was punctured bilaterally with 25G needles and ethiodized oil was injected. After visualization of the cisterna chyli, a 22G Chiba Needle was used to access it. Due to its reduced size, TD cannulation was not feasible. Therefore, further injection of ethiodized oil was performed and the lymphatic leak was observed. After 48 hours, TT drainage reduced (5 ml/kg) and computerized tomography showed a reduction of CPE. 1 week after the procedure, clinical and radiological improvement was observed. Conclusion: CPE in univentricular patients results from iatrogenic lesions during palliative procedures or as an outcome of the increased lymph flow due to increased central venous pressure in patients with lymphatic anatomic variants.1 ILG is a low-risk procedure capable of identifying and treating the source of leakage.2 In this case, due to incapacity of TD cannulation, further use of ethiodized oil was implemented and successfully controlled the effusion. 108944 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Rare Association between Heart Failure and Late Onset Pompe Disease: A Case Report CAROLINA TISOTT BURTET1, Amanda Hillesheim Schuck1, Luisa Gailhard Brito1, Rafaella Magni Berthier1, Olga Sergueevna Tairova1 (1) Universidade de Caxias do Sul (UCS) Introduction: Pompe disease or glycogen storage disease type II (GSD II) is a rare hereditary autosomal disorder, whose incidence reaches 1:50.000. It's caused by gene mutations that encodes the acid alpha-glucosidase enzyme that is responsible for the glycogen degradation - mainly in the muscles. Therefore, this hereditary disease may cause symptoms such as muscle weakness, unsteady gait and cardiorespiratory failure. It can be categorized as early onset Pompe disease (less than 12 months age) or late onset Pompe disease (more than 12 months age), and it is usually known based on the onset symptoms and on the presence or absence of cardiomyopathy. Case Description: 53 year-old female patient with a heart failure history. The patient has been diagnosed with Pompe disease at 34 years of age, and has the family history of two brothers with the same disease. In the last 20 years, it progressed with dyspnea during physical exercise, global strength reduction with predominance in the right hemibody, associated with degenerative anatomical changes. In addition, it presented significant worsening in the lower limbs in the last 5 years. Physical examination: altered gait phases, decreased balance, altered cognitive and verbal level and decreased coordination of selectivity. Complementary Tests: Echocardiogram with ejection fraction (EF) of 37%, eccentric hypertrophy, diastolic dysfunction and systolic dysfunction with a pattern of relaxation deficit; normal catheterization. Patient has no conditions of motor physiotherapy due to the lack of physical fitness. Conclusion: Late-onset Pompe disease usually progresses with a less aggressive presentation and without major cardiac involvement. Despite that, the patient evolved into heart failure with reduced EF. Then, it is possible to propose an association between this condition and late Pompe disease. Although there are few reports in the literature that demonstrate this association, we can conclude that, even if it is rare, it may be possible to find this condition not only in early onset disease. 108971 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY No-Reflow Phenomenon: Alternative Treatment Technique for Patients in the Public Health System RAFAELA OLIVEIRA LEITE1, Bibiana Guimaraes Maggi2, Marcelo Sabedotti2, Rafael Massuti2, Leandro Gazziero Rech2 (1) Fundacao Universidade de Caxias do Sul; (2) Hospital Geral de Caxias do Sul Introduction: The no-reflow phenomenon is defined by the lack of myocardial perfusion despite the opening of the coronary vessel in the context of primary percutaneous coronary intervention (PPCI) after stenting, with no presence of dissection, mechanical obstruction, significant residual stenosis, or spasm. Angiographic evaluation is done by assessing the contrast flow beyond the PPCI location to the distal vessel and is related to an increased risk of major cardiovascular events. To solve this phenomenon, intracoronary infusion of adenosine distal to the stent, by microcatheter, can improve the angiographic pattern. However, in the Brazilian public health care system, also known as Sistema unico de Saude (SUS), PPCI doesn't contemplate microcatheter due to its high cost, making alternative techniques necessary. Case Report: A 70-years-old male, with no previous comorbidity, was hospitalized due to typical chest pain without signs of hemodynamic instability. Complementary tests demonstrated an electrocardiogram with ST-segment elevation on the anterior-septal-lateral and high lateral walls, glomerular filtration rate of 43 mL/min/1,73 m2 and elevated troponin levels (3,9, for a reference of 0,014). Cardiac catheterization, performed through a puncture of the right radial artery, demonstrated ostial occlusion of the anterior descending artery. The left main coronary artery was cannulated with an EBU 4 (6F) catheter, followed by access of a 0,014 guidewire, with the thrombus burden aspiration with an Export(r) Medtronic aspiration catheter and circulation returned. When implanting the drug-eluting stent, the no-reflow phenomenon occurred. For its management, we positioned an aspiration catheter distal to the stent, and administered 1,2 mg of adenosine intracoronary, reestablishing the vessel flow (TIMI 3, BLUSH 3). The patient was transferred to the ward, where he remained asymptomatic until discharged after 6 days. Conclusion: The technique of distal infusion of adenosine through a thrombus aspiration catheter is effective and can be used on the SUS as an alternative to the microcatheter. 108972 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Intraaortic Balloon: Therapeutic Alternative for Treatment of Patients with Acute Coronary Syndrome RAFAELA OLIVEIRA LEITE 1, Elisa Rocha Nonemacher1, Gabriel Almeida Krul1, Marcelo Sabedotti2 (1) Fundacao Universidade de Caxias do Sul; (2) Hospital Geral de Caxias do Sul Introduction: Temporary short - and intermediate-term mechanical circulatory support devices (MCSD) may be used as an escalation strategy to manage situations like cardiogenic shock (CS). The selection of an MCSD depends on the specific indication for hemodynamic support, the urgency of need, costs, and patient-related or device-related risks. The main etiology of CS is acute myocardial infarction (AMI), with seven percent incidence and evolving with loss of up to forty percent of left ventricular function. This study aims to report and discuss a case of acute myocardial infarction with ST-segment elevation associated with occlusion of the left main coronary artery evolving to CC and the use of an Intraaortic balloon pump (IABP). Case Report: A 40-years-old male, previously diagnosed with systemic arterial hypertension arrive at the hospital because of an acute myocardial infarction with ST-segment elevation. His physical examination demonstrated signs of hemodynamic instability, a Killip score of four (suggesting CS), and preserved neurologic status. High-sensitive troponin of the admission was 0,084 (reference of 0,014) and an electrocardiogram demonstrated sinus tachycardia, ST-segment elevation of 7 mm in aVR, and ST-segment depression in anterior-septal-lateral and inferior walls. The patient was promptly referred for early intervention. We performed coronary angiography, which demonstrated left main coronary artery occlusion. The thrombus burdens were aspirated with restauration the coronary flow, and then there was insertion a drug-eluting stent on the left main coronary artery towards the anterior descending artery. We opted for the implantation of an IABP after the procedure, for 24-hour duration support. The patient underwent intensive care for 72-hours. He was successfully discharged after ten days, asymptomatic, with orientation for optimized therapy, request for outpatient care, and cardiac rehabilitation. Conclusion: Knowing that CS increases the morbidity and mortality of patients, it is necessary to evaluate the use of MCDS by the Heart Team. However, the available evidence does not support the routine use of IABP in most patients with AMI. There is evidence that IABP can be an extremely important adjunct in the treatment of these patients, reducing hospital mortality and myocardial injury. Therefore, the technique must be proposed in cases of AMI with rapid clinical deterioration. 108974 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Multicavitary Mixoma: Case Report LEO CHRISTYAN ALVES DE LIMA1, Leo Christyan Alves de Lima1, Hildeman Dias da Costa2, Laura Jane Franca Lacerda1, Milena Stephanie Alves Matos3 (1) Centro Universitario Sao Lucas (UniSL); (2) Universidade Federal de Rondonia (UNIR); (3) Secretaria de Estado da Saude de Rondonia Introduction: Primary cardiac tumors are extremely rare, with an incidence of less than 0.1%. In adults, most benign lesions of the heart are myxomas, accounting for more than 75% of cases. Case Description: Male, 48 years old. A magnetic resonance imaging and transthoracic echocardiogram were performed for diagnostic investigation due to chest pain, which showed an enlarged right atrium (RA) with a mass pedunculated to the interatrial septum, irregular, mobile, invading the right ventricle (RV) in atrial systole, measuring 44 x 35 mm. In the left atrium (LA), oval mass, adhered to the interatrial septum, regular contours, measuring 15 x 11 mm. In RV, oval, subvalvular mass, measuring 19 x 14 mm. The images suggested myxoma in the right atrium and thrombus in the RV and LA, and surgical treatment was proposed. Intraoperatively, excision of the tumor that invaded the entire right atrium was performed, in addition to resection of the mass in the LA and RV, with resection of the atrial septum where the pedicle was located. The septal defect was closed with a continuous suture pericardium patch. He was taken to the ICU and discharged after 4 days. The anatomopathological result was positive for myxoma. Discussion: Differently from the preoperative imaging exams, where two thrombi and one myxoma were suspected, they were confirmed and the three masses were confirmed for myxoma. The vast majority of myxomas are located in the left atrium (LA), the biatrial ones being infrequent and even rarer when associated with the LV location. Conclusion: Due to the location of multicavitary myxoma and less prevalent prevalence, this report shows a rare and atypical morphological presentation of myxomas, with a classic diagnostic method, satisfactory recent postoperative surgical result and good prognosis. 109045 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Use of Fibrinolytics 14 Days After an Episode of Pulmonary Thromboembolism Evolving with Hemodynamic Stability, But with Significant Pulmonary Arterial Hypertension and Limiting Symptoms MIKE VINICIUS CANTO DE ANDRADE1, Karina Baltor Cabral1, Rizia Carla da Silva Leopoldino1, Sthephany Yamaguchi de Melo1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia Introduction: Pulmonary thromboembolism (PTE) has variable clinical conditions. They may be completely asymptomatic or there may even be situations in which massive emboli lead the patient to death, and the diagnosis only through necropsy is not uncommon. Fibrinolytic treatment is indicated for patients who develop clinical instability. However, the establishment of this therapy for hemodynamically stable patients with pulmonary hypertension and/or right ventricular dysfunction is controversial. Case Report: Female, 34 years old, obese, no previous history, taking oral contraception. Reports an episode, 12 days before, of intense chest pain which radiated to her back along with pre-syncope and malaise. Since then, she has maintained dyspnea and fatigue on minor exertion. Physical examination: tachycardia and tachypnea, although hemodynamically stable; normal respiratory and cardiac auscultation. Electrocardiogram: sinus tachycardia (120 bpm) and S1Q3T3 pattern. Chest radiography: no changes. Arterial blood gases without hypoxemia. Elevated D-dimer, Troponin T and BNP. Transthoracic echocardiogram: right chamber dilation, significant right ventricular (RV) dysfunction, good left ventricular (LV) function. Pulmonary artery systolic pressure: 68 mmHg. Normal lower limb venous Doppler. Chest CT angiography: Signs of bilateral submassive thromboembolism. Full dose Enoxaparin was started on the 12th day and chemical thrombolysis was performed by an infusion of 100 mg of thrombolytic recombinant human tissue plasminogen activator (rTPA) in 2 hours (on the 14th day). She improved the symptoms, being discharged. Oral Rivaroxaban was prescribed. A transthoracic echocardiogram performed 3 days later revealed normalization of the right chambers, RV systolic function, and pulmonary artery pressure. Conclusion: Patients with hemodynamically unstable PTE should receive thrombolytic treatment as early as possible; preferably within the first 48 hours. However, if the clinical picture persists, it can be performed up to 14 days after the acute event. In hemodynamically stable patients with signs of RV dysfunction on echocardiography, the use of fibrinolytics is controversial. The use of thrombolytic in this case allowed a significant improvement in the patient's clinical condition, even though it was performed 14 days after the initial diagnosis. The use of the new oral anticoagulants also allows effective, safe anticoagulation and early hospital discharge. 109079 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIO-ONCOLOGY Right Atrial Metastasis of Renal Cell Carcinoma NICOLAS HENRIQUE BORGES1, Ana Paula Guimaraes Feuerschuette1, Jamylle Araujo Dias dos Santos2, Paulo Andre Bispo Machado-Junior1, Gustavo Gavazzoni Blume1 (1) Pontificia Universidade Catolica do Parana (PUC-PR); (2) Hospital Santa Casa de Misericordia de Curitiba Introduction: Renal cell carcinoma (RCC) is a solid lesion responsible for 90% of neoplasms of renal origin. It is classified as an aggressive, lethal tumor with high metastatic power in rare and uncommon locations. Tumor growth can extend to the intravascular environment through the renal veins (RVs) to the inferior vena cava (IVC) with an incidence of 15% in patients diagnosed with CRC, in addition, there is an additional extension of the tumor, which can reach the right atrium (RA), being considered rare and present in 1% of cases. Clinical Description: Female patient, 68 years old, with a previous history of hypertension using hydrochlorothiazide 25 mg/day and hyperthyroidism using tapazole 10 mg/day, sought medical attention with complaints of palpitations and asthenia on minor exertion. In the investigation, exercise stress test was limited by fatigue, indicating functional class III (NYHA), and transthoracic echocardiogram showed a diastolic dysfunction with concentric remodeling of the left ventricle, in addition to the presence of a mobile mass inside the right cavities. On admission, she was dyspneic (RR: 20 mrpm), hypertensive (BP: 140 x 80) and presence of a murmur in the tricuspid focus. MR Angiography report an expansive cortico-medullary lesion in the lower 2/3 of the right kidney, with a central area of necrosis. There was involvement of the ipsilateral renal vein, which showed a filling, suggesting a tumor thrombus that extends to the inferior vena cava and into the right chambers. Cardiac MRI revealed dumbbell-shaped intracavitary mobile mass with protrusion through the tricuspid ring. The patient underwent a total nephrectomy, venous system thrombectomy and retroperitoneal lymphadenectomy. She remained under ICU for 3 days and stay under observation before, being discharged. Biopsy confirming a unifocal, histological grade G3, clear cell renal cell carcinoma of Fuhrmann. The patient presented an excellent evolution only taking medications. Conclusion: Cardiac metastasis to the right atrium is rare in patients with renal cell carcinoma. In our case report, surgery was effective for clinical improvement. 109175 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Recurrent Takotsubo Syndrome in Postmenopausal Woman PEDRO HENRIQUE ROSA E SILVA2, Pedro Henrique Rosa e Silva2, Jairo Rosa e Silva Junior3, Thiago Quinaglia4, Maria A Delbin1 (1) Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas-SP; (2) School of Medical Sciences, University of Campinas (UNICAMP), Campinas-SP; (3) Climecardio, Centro Integrado de Clinica Medica e Cardiologia, Ribeirao Preto-SP; (4) Discipline of Cardiology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas-SP Introduction: Takotsubo Syndrome (TTS) is an acute cardiac syndrome characterized by typical regional wall motion abnormalities that reflect impairment of myocardial contractility. TTS predominantly affects postmenopausal women and is often preceded by emotional stress. The case report was approved by the Ethics Committee (CAAE 45476521.9.0000.5404). Results: A 69-year-old postmenopausal woman with hypothyroidism, type 2 diabetes mellitus, systemic hypertension, dyslipidemia and history of chronic anxiety had in 2/6/2013 an intermittent chest pain accompanied by dyspnea and triggered by emotional stress. The ECG showed an inverted and peaked T wave in the anterolateral and inferior wall, ECHO showed apical segments dyskinesia with aneurysmatic dilatation and coronary angiogram revealed no evidence of coronary artery disease, the patient was diagnosed with TTS. On 10/14/2015, the 71-year-old patient presented sudden symptoms of typical chest pain, accompanied by malaise and diaphoresis, also triggered by emotional stress. The ECG showed an inverted symmetrical and spiked T wave in anterior wall, the left ventricle (LV) ECHO showed the wall entire apex and basal portion hypokinesis, with global contractile function moderately depressed, and coronary angiogram revealed normal coronary arteries and alteration of LV segmental contractility with mild global systolic dysfunction, being diagnosed with TTS. At 74-year-old, on 11/25/2018 the patient presented typical chest pain, dyspnea and diaphoresis, triggered by emotional stress. The ECG showed an inverted and spiked T wave in the septal wall and ECHO showed alteration of segmental mobility in the septal wall associated with mitral regurgitation. Due to the previous medical history of TTS and to the similarity of the clinical conditions with previous events the coronary angiogram wat not performed, being diagnosed with TTS recurrence. In all events, the patient was admitted to the intensive therapy unit for five days with treatment for acute chest pain protocol and hemodynamic support. The ECG and ECHO changes were completely reversed. Years later a myocardial scintigraphy was performed showing no sign of sequels from the events. Conclusion: The report presented a case of recurrent TTS triggered by emotionally stressful events in postmenopausal woman, two events with a differential diagnosis with coronary angiogram. 109176 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Transcathetter Implantation of Aortic Valve in a Patient with a Single Ostium Anomaly of the Coronary Artery with Left Sinus of Valsalva Origin and High Anatomical Risk for Coronary Occlusion FRANCIELLE GODOI SANTOS1, ENZO OKU MARTINAZZO1, ROMULO FRANCISCO DE ALMEIDA TORRES2 (1) Pontificia Universidade Catolica do Parana; (2) Hospital Marcelino Champagnat Introduction: Coronary obstruction (CO) during the transcatheter aortic valve implantation (TAVI) procedure remains an important complication due to a high mortality rate. Its main risk predictors are low origin of coronary ostia, narrow sinus of valsalva and valve-in-valve procedures. Coronary protection (CP) with guidewire and eventual stent implantation is used in patients at high risk for CO in order to increase the safety of the procedure. This study reports the case of a patient with symptomatic severe aortic stenosis who underwent TAVI with the CP technique. In the pre-intervention evaluation, she presented high risk predictors for CO and a rare anomaly of coronary origin. Case Description: An 82-year-old patient was admitted to a tertiary hospital with heart failure. The transthoracic echocardiogram showed the presence of low-gradient normoflow aortic stenosis. Aortic valve calcium score was performed, which reinforced the presence of severe aortic disease. The evaluation with CT angiography showed the presence of a single ostium-like anomaly of the coronary artery originating in the left sinus of valsalva with a low origin in relation to the plane of the annulus. After evaluation by the institutional Heart Team, she underwent TAVI with the CP technique. Conclusions: This report demonstrates the feasibility and safety of the coronary CP technique during the TAVI procedure in a patient with a rare coronary anomaly and at high risk for CO. 109237 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Infective Endocarditis by Proteus Mirabilis: A Rare and Defiant Association NICHOLAS VINCENT LEE1, Nicolas Henrique Borges1, Rosane Carolina Paes de Lira2, Paulo Andre Bispo Machado Junior1, Gustavo Gavazzoni Blume1 (1) PONTIFICIA UNIVERSIDADE CATOLICA DO PARANA - PUC/PR; (2) HOSPITAL SANTA CASA DE CURITIBA - HSC Introduction: Infective Endocarditis (IE) is an uncommon disease with high morbidity and mortality, being commonly associated with gram-positive microorganisms. The IE by Proteus mirabilis, gram-negative, it's rare, difficult to diagnose and the treatment is controversial, being necessary a fast intervention to avoid severe complications. Case Report: Healthy young patient, come to the emergency room with symptoms of asthenia and progressive dyspnea for the last 2 months. On physical examination, the patient had a systolic murmur in aortic focus with irradiation to the carotid arteries. The echocardiogram shows us a severe double aortic valvar lesion and an importante systolic disfunction (Simpson's Ejection Fraction of 29%), being indicated aortic valve replacement surgery. While waiting for the surgery, the patient developed bacteremia secondary to phlebitis in peripheric venous access, hemoculture with Staphylococcus epidermidis was positive, initiated a guided antibiotic regimen (oxacillin 500 mg 4/4 h IV). However, the patient remained feverish with high inflammatory markers, evolving to sepsis, and a new antibiotic regimen was started (vancomycin 1000 mg 12/12 h IV). Eight days after the diagnosis of the infeccion, news hemocultures revealed the presence of Proteus mirabilis in blood, being administrated a new antibiotic treatment (cefepime 2g 8/8 h IV) but without a good response. After multiples antibiotics and roled out other infectious foci, a new transesophageal ecocardiogram identify a laminar image in the aortic root suggestive of abscess without vegetations. Opted of emergency surgery, the diagnosis was confirmed of abscess valvar, but despite the intervention, the patient died. Conclusion: The present report case demonstrated a rare and defiant association of IE by Proteus mirabilis with an atypical presentation in echocardiogram (abscess without vegetation) and even with the combined antimicrobial management and surgery, it did not present a favorable outcome. 109261 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Coronary Anomalies, a Rare Diagnosis and an Unfavorable Outcome: Case Report SARA AYRES SOARES DE SOUZA1, Danielle Caiado de Castro Dragalzew2, Felipe Augusto Lima Rodrigues2 (1) Universidade Catolica de Brasilia - UCB; (2) Instituto Hospital de Base do Distrito Federal - IHBDF Introduction: Coronary anomalies (CA) are a group of cardiac malformations that encompass variations as anomalous origin of the left coronary (AOLC) and coronaries fistulas. Those abnormalities are rare (0.2-1.2%) and difficult to diagnose, usually needing an imaging test. Patients with this condition are asymptomatic at onset, however they have a high risk of sudden death. Latest findings include valvular complications, myocardial ischemia, angina and congestive heart failure. As spontaneous resolutions are rare, it is essential to diagnose and treat these cases. Case Report: JRSB 44-years-old woman, hypertensive, under treatment for squamous cell carcinoma of the cervix IIIB. Myocardial Scintigraphy (2018) shows preserved ejection fraction (EF), evidencing high degree of persistent hypoperfusion of the anterior wall and apex of the left ventricle, indicative of fibrosis/hibernating myocardium and apex myocardial ischemia. No follow-up was performed. She presented with acute coronary syndrome (ACS) in 2021. In the same year a coronary angiography showed right coronary artery (RCA) without obstruction, AOLC without possibility of selective catheterization and one fistula communication from the RCA to the pulmonary artery. Transthoracic echocardiogram with an EF of 65%, mild mitral, tricuspid and pulmonary valves insufficiency and septal dyskinesia. Electrocardiogram: diffuse repolarization abnormality and extrasystole. In 2022 patient presented with chest pain and tachycardia in moderate to mild intensity exercises, no findings on physical examination. The patient uses daily metoprolol 100 mg, enalapril 10 mg, simvastatin 20 mg, trimetazidine 80 mg. At the found diagnostic stage, the patient presented with symptomatic cardiac morphological change, and waits for surgical approach. Conclusion: The diagnosis of CA is rare, but important as differential in cases of chest pain. In the present case, this is showed by the imaging tests demonstrating the presence of AOLC and coronary fistula, abnormalities that can evolve with ACS, myocardial ischemia and valve insufficiency as happened. This evolution was favored by the absence of follow-up and proper treatment. The patient is still waiting for surgical approach which will help to avoid unfavorable outcomes. 109297 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Early Diagnosis and Intervention of Eisemenger Syndrome in a Six Months Old Child: A Case Report ERYCLAUDIA CHRYSTIAN BRASILEIRO AGRIPINO1, Matheus Henrique Soares Neves da Silva1, Hanna da Costa Avelar Domingues1, Raquel Travassos Oliveira1, Estefane Ribeiro Melo1 (1) Universidade de Pernambuco - Campus Garanhuns (UPE) Introduction: Eisenmenger syndrome (ES) represents the triad of pulmonary arterial disease, reversal of the central shunt's flow and cyanosis resulting from systemic-to-pulmonary congenital cardiovascular communication. The key to decide management is the detection and treatment of the cardiac defect before development of pulmonary hypertension, preferably during early childhood. In this case-report, it's described the diagnosis and following management of an ES secondary to intracardiac communication and a right-to-left shunt in a 6 months old child. Case Report: A 6 months old girl presented with respiratory discomfort since birth, developmental delay and low weight gain was admitted to a tertiary hospital to undergo clinical evaluation. On examination, the patient presented a pansystolic murmur (5+/6+) and signs of respiratory failure. The remainder of the examination was normal. On the third day of hospitalization, it was ordered a transthoracic echocardiogram (TTE), that demonstrated interatrial communication with bidirectional shunt (right-to-left predominance), interventricular communication with bidirectional shunt (left-to-right predominance), moderate pulmonary hypertension (PAH), patent ductus arteriosus (PDA) with left-to-right shunt and relative mitral valve stenosis. On the fourth day, it was initiated therapy with spironolactone 1 mg/kg/day, digoxin 0,01 mg/kg/day and captopril 1 mg/kg/day. She was referred for a cardiological surgical service on the sixteenth hospital day. Atrial septoplasty and ventricular septoplasty with ligation of the PDA were performed. In the last week of hospitalization, a new TTE was ordered, which demonstrated intact atrioventricular septums, preserved biventricular systolic function and pulmonary pressure gradient unsuggestive of PAH. She was discharged after 43 days of hospitalization with a long-term therapy plan with furosemide 1 mg/kg/day, spironolactone 1 mg/kg/day and referral to ambulatory care. Conclusion: ES is a truly devastating condition, mainly without the early diagnosis and adequate treatment. Most of the patients tend to suffer an early death due to heart failure, arrhythmias and thromboembolic cerebrovascular disease. In this case-report, the early diagnosis associated with clinical and surgical optimized intervention were decisives for the patient's outcome to be modified following the literature recommendations regarding management in such conditions. 109327 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Takotsubo Cardiomyopathy in a Paciente with Panhypopituitarism Resulting in QT Prolongation FILIPE EVERTON SILVA RODRIGUES 1, Joao Gabriel Oliveira de Souza1, Ana Carolina Sampaio Freire1, Victor Oliveira da Cruz1, Alexandre Anderson de Sousa Munhoz Soares1 (1) Universidade de Brasilia - UnB Introduction: Takotsubo cardiomyopathy (TTC) is a reversible left ventricular dysfunction. The initial symptoms mimic acute coronary disease, as patients present with dyspnea, hypotension, syncope, elevated troponin levels and suggestive electrocardiographic changes. Predisposing factors include emotional stress, endocrine disease and adrenal insufficiency. Case Report: A diabetic, hypertensive 50 year old woman with a history of chronic pericarditis and TTC seeked the emergency department presenting chest pain, sweating, hypotension and dyspnea. Transthoracic Echocardiogram showed regional changes in the left ventricle contractile function, suggesting TTC with a left ventricular ejection fraction of 47,6% and cardiac magnetic resonance imaging revealed pericarditis. After hospitalization, she had improvement in the symptoms, being discharged with further ambulatorial investigation scheduled. A week later, she presented with worsening symptoms, with high troponin and D-dimer levels. She developed an episode of unstable polymorphic ventricular tachycardia with QT prolongation, corrected QT (QTc) of 518 ms, needing electrical cardioversion. Upon investigation and questioning the patient revealed a visual impairment that began 6 months prior. With that information and imaging it was diagnosed a brain tumor (very likely a glioma) compressing the pituitary gland. After starting hormonal replacement therapy (HRT), there were no new episodes of arrhythmia. The patient was discharged waiting to begin tumor treatment. Conclusion: Although the evolution of TTC in the majority of cases is favorable, prolonged QTc should be evaluated due to the potential of death. QT prolongation serves as a substrate for ventricular tachycardia and sudden cardiac death, but the occurrence of ventricular fibrillation and its predictors in the disease are still unknown. The exact pathophysiology of TTC is not fully understood. In this case, a panhypopituitarism due to tumor compression might of caused a secondary adrenal insufficiency, resulting in glucocorticoid deficiency, hyponatremia and related hypoglycemia, which may have induced a catecholamine release resulting arrhythmia and the recurrence of abnormal wall motion. To guide clinical decision-making, patients with cardiac abnormalities should be checked for hormonal alterations, knowing the possible connection between endocrine disorder in TTC and torsades de pointes, resulting in a potential therapeutic opportunity with HRT. 109329 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY 22Q11 Deletion Syndrome (Velocardiofacial/Digeorge Syndrome) and Congenital Heart Diseases: Report of Two Cases Together with a Literature Review CAROLINA GUIMARAES HERZOG1, Marco Antonio Vinciprova Dall'Agnese1, Pedro Dutra Batista1, Gabriel de Paula Alves1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre - UFCSPA Introduction: The 22q11 deletion syndrome (22q11DS) is considered the second most known genetic cause of congenital heart disease (CHD). Here we reported two patients with different types of CHD presenting 22q11DS. Cases Descriptions: The first patient was a three-year-old girl, who was referred to the service due to a diagnosis of type A aortic arch interruption. She underwent cardiac surgery shortly afterwards, and developed hypoparathyroidism. Abdominal ultrasound revealed a left renal agenesis. The patient also presented intermittent strabismus, high palate, micrognathia, posteriorly rotated right ear, left ear in faun and umbilical hernia. Karyotypic analysis was normal. However, a posterior evaluation through the use of fluorescence in situ hybridization (FISH) technique confirmed the diagnosis of 22q11DS. The second patient was a two-day-old girl who presented an echocardiography with evidence of a type I truncus arteriosus. She had already been submitted to karyotypic evaluation during the prenatal period - due to an increased nuchal translucency measurement -, which was normal. The patient presented in her clinical evaluation blepharophimosis, posteriorly rotated and low-set ears, and clubfoot on the right. The use of the FISH technique verified the diagnosis of 22q11DS. Conclusion: The 22q11DS presents an important association with CHDs, especially with the conotruncal ones. About half of the patients presenting type A interrupted aortic arch and one third of those with truncus arteriosus disclosed 22q11DS. As a consequence, patients with those CHDs should always be carefully evaluated regarding the existence of this syndrome. 109373 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Syphilitic Thoracic Aortic Aneurysm in a Young Patient - Case Report MARIA CLARA SERAPIAO FERREIRA1, Maria Clara Serapiao Ferreira1, Alessandro da Costa Machado2, Fernanda Snovarski Mota3, Alberto Acosta Hermida3 (1) Universidade Federal da Integracao Latino-Americana (UNILA); (2) Hospital Municipal Padre Germano Lauck (HMPGL); (3) Hospital Ministro Costa Cavalcanti (HMCC) Introduction: Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum; when not properly treated, it can progress to tertiary syphilis and produce cardiovascular lesions, mostly affecting the aorta. Syphilitic aortic aneurysm, although rare, is still a possibility. We report the case of a young patient with an aortic arch aneurysm susceptible to rupture of syphilitic origin. Case Description: Male, 37 years old, with progressive dyspnea for 5 days, dry cough, mainly during inspiration, evolving with hoarseness for about 1 day. Hypertensive without treatment and smoker, associated with history of multiple sexual partners, not using protection. There is no history of STI or recent trauma. On physical examination, a hypertensive patient 140 x 80 mmHg (left upper limb) and 160 x 90 mmHg (right upper limb), normocardic, eupneic on room air. On cardiac auscultation, he had intense diastolic murmur (+4/+6) associated with thrill in aortic focus and hyperphonetic heart sounds. Chest angiotomography showed an aortic arch aneurysm, with an extension of 11,5 cm, with a mural thrombus in the right lateral portion, associated with tracheal deviation due to mass effect. Coronary computed tomography angiography showed no significant coronary lesions. Therefore, it was indicated a surgical approach for aneurysm repair, with aortic reconstruction and implantation of a 28 mm Dacron tube, without complications. Afterwards, considering the patient's history and the aneurysm characteristics, especially its location, nontreponemal test was requested, being positive, with a VDRL of 1:128. For that reason, the treatment for tertiary syphilis with benzathine penicillin was initiated. The patient evolved uneventfully, was discharged six days after the operation, with outpatient follow-up. Conclusions: Although the treatment of syphilis with benzathine penicillin is effective and widely available, and the manifestations of tertiary syphilis are uncommon, the diagnosis of syphilitic aortitis should be considered. We must consider that there is a direct relationship between the sociocultural level of the patient and the development of the disease. Thus, the case demonstrates that the late diagnosis of syphilis causes important cardiovascular repercussions, which require immediate recognition and surgical approach to obtain a favorable prognosis. 109420 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Aortic Perforation: A Rare but Serious Complication in Pacemaker Implantation KESLLY KRAUSPENHAR CUCHINSKI1, Eduardo Bartholomay1, Liara Eickhoff Coppetti1, Melissa Nadal Duarte1, Tilae Steinmetz Soares1 (1) Universidade Luterana do Brasil - ULBRA Introduction: Pacemaker implantation is a safe procedure and widely used in clinical practice. Intercurrences are infrequent, but a serious complication can occur, such as vessel perforation. The present study aims to report a case of cardiac pacemaker insertion with unfavorable outcome due to ascending thoracic aorta perforation and to discuss ways to avoid this rare complication. Case Description: Male patient, 71 years old, submitted to pacemaker implantation due to sinus dysfunction and Wenckebach type 2 atrioventricular block with a narrow QRS. The device chosen was a DDD pacemaker with ventricular stimulation through the conduction system by the bundle of His. The implantation was performed by placing the atrial lead in the anteroseptal region through posteroanterior radiographic visualization and the ventricular lead by radiological orientation and by the His bundle electrogram in the septal region, close to the membranous septum. The procedure was performed with a duration of 1.5 hours with 7 min of radioscopy. After arriving in the intensive care unit (ICU), the patient showed cardiac tamponade detected by echocardiography. Pericardial drainage of 100 ml of blood was performed with resolution of the hemodynamic condition. The patient was referred for atrial lead replacement, since the His bundle lead was in the septum. During anesthetic preparation, the patient presented cough and sudden hemodynamic collapse, evolving to cardiorespiratory arrest. With the opening of the pericardium, a large amount of arterial blood was detected. It was opted for emergency sternotomy and direct cardiopulmonary resuscitation (CPR). A small screw tip of the atrial electrode was visualized, which had perforated the atrium and "clamped" the aorta. The bleeding was manually stopped and the spontaneous circulation returned after 60 minutes of CPR. The atrial electrode was repositioned in the anterior region of the right atrial appendage and the sternum was sutured. The patient was referred to the ICU, but evolved with hemodynamic shock due to systemic inflammatory response syndrome, passing away 4 days after the procedure. Conclusion: Aortic perforation by atrial lead is a rare event described in few cases in literature; however, it is of extreme clinical relevance due to its high mortality. Therefore, we suwe suggest that the right oblique view should always be performed to certify the location of the anterior lead, aiming to avoid this rare, yet tragic complication. 109425 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Congenital Complete Heart Block in a Newborn Due to Maternal Sjogren's Syndrome: A Case Report PEDRO GUSTAVO STEVANATO DE OLIVEIRA1, Georgia Marques Jardim1, Nadine Edda Correa2, Gustavo Gianesini1, Neivis Cubillos1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre; (2) Universidade Federal de Santa Catarina, Campus Ararangua Introduction: Congenital complete heart block (CHB) occurs in approximately 1/20,000 live births and is associated with low ventricular rate and reduced cardiac output, leading to heart failure and fetal hydrops. Congenital CAVB is associated with a significant increase in mortality and morbidity and may or may not be secondary to immunological processes. The transplacental passage of maternal anti-RO and anti-La antibodies, which causes damage to the fetal conduction system, is responsible for congenital CHB of immunological etiology. Case Description: Female patient, 31 years old, Sjogren's syndrome with idiopathic thrombocytopenic purpura (remission for four years) and depression. The fetus was diagnosed with CHB during the prenatal follow-up of her fifth pregnancy. She followed up with fetal cardiology through echocardiograms that showed bradycardia around 42 bpm, ventricular rate around 47 and no signs of hydrops. The newborn (NB) was born full-term with high levels of anti-RO and anti-La, with a heart rate of 45 bpm without clinical hemodynamic repercussions. A postnatal echocardiogram showed ventricular chambers' enlargement and mild mitral and tricuspid regurgitation. A 24-hour holter monitoring confirmed CHB and QTC interval increase. After nine days, the patient underwent surgery to implant a pacemaker (Median Sternotomy: Implantation of an epicardial bipolar electrode in the left ventricular tip). He was presented with mild metabolic acidosis in the immediate postoperative period and progressed well, with a heart rate of 100 bpm, being extubated the next day, with hospital discharge one week after the procedure. Conclusion: Congenital CABG is of significant risk to the newborn and may be secondary to immunological mechanisms, such as Sjogren's syndrome, as seen in this case by the high anti-RO and anti-La levels in the NB. It can be treated by implanting a pacemaker with good evolution. 109438 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Electrical Cardioversion in the Resolution of Atrial Flutter in a Newborn: A Case Report PEDRO GUSTAVO STEVANATO DE OLIVEIRA1, Nadine Edda Correa2, Georgia Marques Jardim1, Gustavo Gianesini1, Barbara Zottis1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre; (2) Universidade Federal de Santa Catarina, Campus Ararangua Introduction: Atrial flutter (AF) is a supraventricular tachyarrhythmia, rare in neonates, marked on the Electrocardiogram (ECG) by irregular, rapid atrial activity with 280-500 beats per minute (bpm), generally associated with 2:1 atrioventricular (AV) conduction. It usually affects children with cardiac malformations, but it can also develop in newborns with normal cardiac anatomy. Sinus rhythm can be restored with antiarrhythmic drugs, electrical cardioversion, or transesophageal stimulation. Case Description: 8-day-old male newborn, cesarean delivery due to maternal desire, at term, without complications, with 24-hour Holter showing AF with ventricular response ranging between 105 and 235 bpm, with an average of 168 bpm, in addition to AV conduction in a 2:1 ratio. After five days of finding AF in the exam, propranolol was started, with no adequate response. The patient was transferred to the Pediatric Intensive Care Unit of the reference hospital in the city, where he arrived hemodynamically stable, without vasoactive drugs, on room air, and without the need for oxygen therapy. ECG and echocardiogram were requested, continued monitoring and anticoagulation with heparin 29IU/kg/h was initiated in case of intra-atrial thrombus. Echocardiogram performed the following day showed mild enlargement of the cardiac chambers, biventricular systolic function in the lower limits of normality, mild mitral regurgitation, and absence of intracardiac thrombi. Electrical cardioversion was chosen. Pre-procedure orotracheal intubation was performed with a rapid intubation sequence, an uneventful procedure. Two cardioversion attempts were performed with 2 Joules (0.5 joules/kg) each, successfully after the second. It was documented an electrocardiogram after the procedure with sinus rhythm. The patient was extubated throughout the day without complications. Anticoagulation was suspended 96 hours after cardioversion. He remained hospitalized, stable, without new arrhythmias for seven days after the procedure. He was discharged with a referral for cardiological follow-up within 30 days. Conclusion: Despite being potentially fatal, atrial flutter in neonates has a good prognosis when diagnosed early, with electrical cardioversion representing an excellent therapeutic option, as evidenced in the above case. 109444 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Congenital Atrioventricular Block: Diagnosis, Treatment and Follow-Up in a Child 01 Year and 8 Months Old ISABELLA CAROLINE SOUZA DANTAS1, Marco Arthur Queiroz Passos1, Mary Anny Silva Fonseca1, Tarcisio Esdras Araujo Moura2, Jose Carlos Pachon Mateos2 (1) Faculdade Ages de Medicina; (2) Associacao Beneficente Siria HCOR Introduction: Bradyarrhythmias are rare in children, the main, of significance is the complete atrioventricular block (CAVB), whose reported incidence is one case for every 25,000 live births, being more predominent in females. Children with a normally structured heart, in general, have a congenital etiology and are often linked to the presence of maternal systemic lupus erythematosus (SLE). Case Report: M.E.C.A.A.P., 01 year and 8 months old, presented dyspnea between feedings, low weight gain and syncope for +/-02 months. An electrocardiogram was performed, which showed a CAVB and a transthoracic echocardiogram (ECOTT) with a dilation of the left chambers. In the family history, mother with SLE. On 07/04/2018, an implantation of a definitive unicameral pacemaker by puncture of the left subclavian vein was performed, the electrode was positioned in the middle septum of the right ventricle and atrial loop was performed for growth curve. After implantation of the device, the patient evolved with significant improvement in dyspnea, with no recurrence of any syncope episodes and with the last ECOTT, performed four years after implantation, within normal limits. Conclusion: Congenital CAVB is a rare disorder and occurs due to the pathological changes in the AV conduction system that can be associated or not with congenital heart disease. In 50% of cases, it occurs due to malformation of the conduction system and is associated with structural diseases, the most frequent being left atrial isomerism and corrected transposition of the great arteries. Autoimmune CAVB, associated with maternal anti-Ro and Anti-La antibodies, represents approximately 40% of cases. This pathology can evolve with ventricular dysfunction, severe heart failure and even fetal or neonatal death, justifying the importance of awakening the academic community for early diagnosis and adequate therapy. In the case described above, the patient had signs and symptoms of low cardiac output, syncope and growth issues. In addition, maternal autoantibodies (Anti-Ro and Anti-La) and heart rate lower than 70 bpm were still present with structural heart disease or ventricular dysfunction. For these reasons, a pacemaker was indicated, whose endovascular implant was performed with the atrial loop aiming at the child's growth curve. After implantation of the device, the patient's s symptoms and heart disease improved, in a four-year follow-up. 109474 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Case Report of a Patient Diagnosed with Cat Eye Syndrome Presenting a Total Anomalous Pulmonary Venous Return (TAPVR) WALDEMIR FERRARI JUNIOR1, Mariana Castro Pires1, Julio Pasquali Andrade1, Leonardo Nunes Sanson1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre Introduction: Cat eye syndrome (CES) is a rare disease caused by a partial tetrasomy of chromosome 22. We aim to report a patient with CES presenting a total anomalous pulmonary venous return (TAPVR). Case Description: The patient was the fourth child of a couple with no previous history of similar cases in the family. The child was a non-identical twin and was born by cesarean section, premature, weighing 2,240 g, with a length of 46 cm and a 6/8 Apgar score. The child needed oxygen therapy and mechanical ventilation immediately after birth, when a cardiac murmur was discovered. Due to an anal atresia with a vaginal fistula, the child required a colostomy surgery. Echocardiography revealed a non-obstructive TAPVR. The child underwent a cardiac surgery with 15 days of life, and kept the sternum open in the post-operative period. In the newborn evaluation, a right iris coloboma was also observed, in addition to both bilateral preauricular appendages and pits, micrognathia and a cutaneous appendage at the anus' topology. The karyotype test revealed a partial tetrasomy of chromosome 22, resulting from a dicentric supernumerary marker chromosome: inv dup (22) (pter->q11.2::q11.2->pter). The child evolved with a persistent chylothorax, requiring thoracic drainage and pleurodesis, and died with 2 months old. Conclusion: Congenital heart defects are observed in more than half of patients with CES, especially TAPVR. When patients present extracardiac manifestations, as coloboma, preauricular pits/tags and anal atresia, TAPVR should be investigated. 109582 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Pediatric Hypertrophic Cardiomyopathy Due to Biallelic Pathogenic Variant in ALPK3: A Case Report JOAO VICTOR ANDRADE PIMENTEL1, Julia Souza Diniz1, Beatriz Luduvice Soares1, Joao Paulo Dias Costa1, Emerson Santana Santos1 (1) Universidade Federal de Sergipe Introduction: Alpha-protein kinase 3 (ALPK3) is one of the genes related to the development of cardiomyopathy. Patients with pathogenic variants in ALPK3 may present dilated cardiomyopathy that can progress to hypertrophic cardiomyopathy with poor systolic function. Biallelic pathogenic variants can cause several clinical features, with early-onset cardiomyopathy and extracardiac manifestations. Case Report: A 16-year old male was referred to our cardiogenetics outpatient clinic due to the diagnosis of non-obstructive concentric hypertrophic cardiomyopathy (HCM) at the age of 10. Born from healthy and non-consanguineous parents. He has four siblings without any cardiac conditions. His maternal and paternal grandparents had sudden cardiac deaths. Extracardiac features were also observed (facial dysmorphism, downslanting ears, short neck). Patient has also depression and has been assisted by a psychiatrist. He has been using beta-blocker and fluoxetine. A HCM gene panel found two different pathogenic variants on ALPK3 gene. Genetic studies confirmed that both parents were carriers. Cardiac magnetic resonance showed a maximal wall thickness of 33 millimeters. Conclusion: This case report highlights the importance of searching for the etiology of HCM and the genetic counseling for proper management of patients and their families. 109604 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Subendocardial Calcification and Ventricular Tachycardia of Undetermined Etiology: A Case Report DIEGO ARAUJO SILVA1, Thaisa Moreira Cencao1, Gabriela Rodrigues de Oliveira2, Ricardo Santiago Ferreira Coelho2, Juliano Novaes Cardoso2 (1) Faculdade Santa Marcelina; (2) Hospital Santa Marcelina Myocardial calcification, for the most part, has an etiology related to chronic pericardial diseases of multiple causes (viral, metabolic, rheumatologic). 67% of the patients with cardiac calcification have symptoms of heart failure; 8% have chest pain; 6%, abdominal pain; 4%, atrial arrhythmias; and 5%, symptoms suggestive of cardiac tamponade1. The present study aims at reporting a case considered unprecedented in the literature because although most cases of cardiac calcification are related to constrictive pericarditis, the case in question is a calcification secondary to a subendocardial infarction, not correlated with any identified etiology. A 69-year-old female patient, seen due to complaint of acute vertigo, which evolved with unstable ventricular tachyarrhythmia and in need of electrical cardioversion. After cardiological evaluation, coronary cineangiography was submitted without alterations; However, ventriculography calcifications were identified leading to myocardial resonance imaging for differential diagnosis, which showed: subendocardial calcifications in inferolateral, basal, middle, and apical segments, compatible with subendocardial infarction. Due to the impossibility of surgical removal of the calcifications and the occurrence of ventricular tachycardia, implantation of an implantable cardioverter defibrillator was indicated. The patient presented stabilization of the condition and remains under outpatient follow-up. Unlike what is presented in the literature as the most common, the patient evolved with subendocardial calcifications of unspecified etiology, without a positive clinical history, nor infectious, metabolic, or rheumatological markers identified during the etymological evaluation performed. Subendocardial calcification is very rare, with few studies on this subject being found. Adequate planning and outpatient follow-up should be performed, considering subendocardial calcification, ICD, and the team's experience. 109652 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Aortic Coarctation and Bicuspid Aortic Valve with Severe Regurgitation Being Diagnosed in Adulthood and Treated with Extra-Anatomical Tube Implantation and Valve Plasty MARIA GABRIELA PIMENTA DOS SANTOS1, David Ferreira de Lima Duarte1, Maria Carolina Terra Cola2, Fabio Akio Nishijuka2, Thaissa Santos Monteiro2 (1) Universidade Estacio de Sa/IDOMED; (2) Instituto Nacional de Cardiologia (INC) Introduction: Aortic coarctation (AC) and bicuspid aortic valve (BAV) are commonly associated. Diagnosed of AC must be early. Case Report: A 23 year-old patient diagnosed with AC and BAV after he had been hospitalized due to heart failure. Had many suggestive signs of AC in the physical exam, such as reduced pulse in the lower limbs, significant gradient of blood pressure between upper and lower limbs, and even a disproportion of upper and lower limbs development and signs of a significant aortic regurgitation as well. Echocardiogram (ECHO) identified BAV with severe regurgitation, left ventricle (LV) enlargement with moderate systolic dysfunction, monophasic blood flow in the distal descending aorta and abdominal aorta. Chest x-ray showed enlargement of the heart and erosions of the inferior border of the costal arches. Angiotomography (AT) showed a focal stenosis after the left subclavian artery, multiple collateral vessels and brachiocephalic trunk aneurysm. The initial strategy was to stent the AC and then treat the BAV surgically. The patient was submitted to an attempt of percutaneous treatment, but there was no success in passing the wire guide through the stenosis. It was then performed surgery with extra-anatomical tube implantation and aortic valve plasty with successful results and recovery. Conclusion: AC associated with BAV with significant regurgitation can evolve with significant impairment of the LV, impacting the morbidity and mortality of a young patient. The physical exam can be very helpful in the suspicion of these diagnoses, highlighting the importance of a thorough physical exam. Confirmation with non invasive tests are required, such as ECHO and AT, but catheterization will evaluate the gradient of the AC and often treat the lesion in the same procedure. 110116 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Heyde's Syndrome: Presentation, Pathophysiology and Management RODRIGO BATISTA WARPECHOWSKI1, Thomas Ranquetat Andrade3, Nicholas Travi Dornelles3, Iuri Schwaab1, Paulo Warpechowski2 (1) Instituto de Cardiologia do Rio Grande do Sul; (2) Sociedade de Anestesiologia (SANE); (3) Escola de Medicina da PUCRS Introduction: Heyde's syndrome (HS) is described as a multisystem disorder, characterized by a triad composed of aortic stenosis (AS), angiodysplasia (AD) of the gastrointestinal tract and acquired von Willebrand syndrome (AVWS) type IIA. In this case report, we present the evolution of a patient with HS presenting symptoms of congestive heart failure (CHF) and anemia. Case Report: Female patient, 73 years old, hypertensive, diabetic, dyslipidemic, smoker, with a history of iron-deficiency anemia and atrial fibrillation, admitted for aortic valve replacement. Complains of dyspnea, chest pain and symptoms of CHF. Echocardiogram showed severe aortic valvular stenosis (0,6 cm2), calcified valve leaflets, biatrial overload, left ventricular concentric hipertrofy, and pulmonary hypertension. The patient presented anemia, (Hb 6.9 g/dL), and received packed red blood cells treatment. After 3 days, there was an improvement in her blood count, with acceptable haemoglobin levels. No coronary lesions. Blood transfusion and CHF therapy were performed, with correction of congestion and dyspnea. A valve replacement procedure with biological prosthesis was performed without intercurrences. A new episode of anemia (Hb 6,1 g/dL) due to gastrointestinal bleeding occurred, presenting melena and requiring a new blood transfusion. The patient was discharged with general improvement, with a request for colonoscopy in search of AD. Conclusion: The most accepted AVWS mechanism proposes that in a situation in which shear forces are increased, as in AS, conformational changes occur in the multimers of von Willebrand Factor as it passes through the turbulent flow of a stenotic valve, causing interference in the control of angiogenesis and in the distribution of clotting factor VIII throughout the body. This association provides an important pathophysiological basis that supports valve replacement as a key strategy for long-term resolution of recurrent bleeding. Currently, most patients with HS after valve replacement have a reduction or disappearance of bleeding episodes. Furthermore, transcatheter aortic valve replacement (TAVR) has shown excellent results as well, with fewer perioperatory complications. Despite TAVR reduced risk, there are no differences in outcomes in terms of all-cause mortality in patients with HS undergoing these procedures. In addition, in patients who received bioprosthesis, the risk of recurrence of bleeding was 45% lower than in the mechanical ones group. 109729 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Russell-Silver Syndrome and Congenital Heart Disease: Report of a Rare Association WALDEMIR FERRARI JUNIOR1, Capitulino Camargo Junior1, Julio Pasquali Andrade1, Vitor Reis de Souza1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre Introduction: Russell-Silver Syndrome (RSS) is a genetically heterogeneous condition characterized by the fault of the primordial growth. Our goal was to report a case of RSS presenting transposition of great vessels. Case Description: The patient is the fifth child of a non-consanguineous couple, without history of similar cases in the family. The child was born of vaginal delivery, with 37 weeks of gestation, weighing 1,785 grams and with Apgar scores of 7/8. He was hospitalized in the neonatal intensive care unit requiring oxygen therapy. In this period, there was suspicion of a congenital heart disease. Echocardiography showed transposition of great vessels, persistence of the ductus arteriosus, ventricular septal defect and atrial septal defect of patent oval foramen type. The child underwent cardiac surgery and resection of the ductus arteriosus, as well as recovery and atrial septal defect repair on the thirteenth day of life. In the physical examination, with 11 months old, growth retardation was observed, upslanting palpebral fissures, epicanthic folds, wide and low nasal root, high arched palate, micrognathia, bilateral single palmar crease, fifth fingers clinodactyly, bilateral camptodactyly from the second to the fifth hand fingers, lower lombo asymmetry (the left member was smaller than the right), overlapping toes and hypotonia. He evolved with neuropsychomotor delay and feeding difficulties. His karyotype test was normal. Conclusion: The sum of the presenting findings our patient was compatible with the diagnosis of RSS. The pre and postnatal growth retardation and limb asymmetry are considered major criteria for diagnosis. Congenital heart diseases are rarely described among these individuals. 109770 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Necrotizing Aortitis with Aortic Dissection and Libman-S Sacks Endocarditis in a Lupus Patient DAVID FERREIRA DE LIMA DUARTE1, Maria Gabriela Pimenta dos Santos1, Maria Carolina Terra Cola2, Fabio Akio Nishijuka2, Thaissa Santos Monteiro2 (1) Universidade Estacio de Sa/IDOMED, Campus Citta e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (2) Instituto Nacional de Cardiologia Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease. It is associated with multisystem organ damage mediated by autoantibodies and immune complexes. Lupus Aortitis is an uncommon and potentially fatal complication of SLE. Case Description: Female 37-year-old, known to have SLE 15 years ago and Sjogren's syndrome. Has had, lupus nephritis type IV, sensory motor polyneuropathy, idiopathic thrombocytopenic purpura and depression. Reports irregular use of azathioprine and hydroxychloroquine when presented a chest pain radiating to the neck and jaw after emotional stress, which lasted 15 minutes. Transesophageal echocardiographym identified an aneurysm of the ascending aorta measuring 4.9 cm with dissection 1.6 cm above the aortic valve, and severe tricuspid regurgitation with overload of the right ventricle. Angiotomography confirmed the diagnosis of aortic dissection Stanford A, Debakey I. was performed with replacement of the ascending aorta and arch, resection of vegetations in the tricuspid valve (TV) that was identified through histopatological analysis as thrombus, and plastic repair of TV. Controlled angiotomography after surgery identified several saccular aneurysms in the aortic root. FDG pet scan was performed to assess the SLE activity in the aorta, which identified inflammatory activity. Adjustments of the medical treatment were made in order to control lupus activity before the patient can be submitted to another surgery. Conclusions: Lupus aortitis is a rare and severe complication of SLE, and surgical treatment as well as controlled of the rheumatological disease are required. The FDG pet scan can help in assessing the inflammatory activity of the disease, determining adjustments of the medical treatment and the best timing for surgery. 109783 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Association between COVID-19 and Rapid Progression of Graft Vascular Disease in Late Heart Transplantation: Unexplored Link or Spurious Relationship? BRUNA DE ALMEIDA FREIXEDELO1, Mateus de Sousa Cavalcante1, Dara Medeiros Mendes1, Jefferson Luis Vieira2, Leandro Cordeiro Portela1 (1) Universidade Federal do Ceara (UFC), campus Sobral, Sobral/CE-Brazil; (2) Hospital de Messejana Dr. Carlos Alberto Studart Gomes, Fortaleza/CE-Brazil Introduction: Heart transplant (HT) recipients are at an increased risk of complications from COVID-19 due to chronic immunosuppression and comorbidities. Yet, no immunological link has been proven to explain an association between COVID-19 infection and late post-HT complications, including graft vascular disease (GVD) or late rejection. Case Description: Male patient, 63 years old, with a history of HT for 18 years, admitted for HF and LVEF 35% one month after COVID-19 and change of immunosuppressive regimen due to unavailability of sirolimus in the health system. The pharmacological stress echocardiogram with dobutamine had been normal in the previous year. Diagnostic screening with endomyocardial biopsy (EMB) and panel of antibodies (including CD3, CD68, CD20 and C4D) ruled out cellular and/or humoral rejection, showing extensive interstitial and endocardial fibrosis, with myocytic hypertrophy and ischemic pattern; coronary angiography revealed significant multivessel coronary disease, with ectasias and rosary bead-like occlusions, confirming the clinical suspicion of GVD. Subsequent intracoronary ultrasound identified a minimum luminal area of 5 mm2 and the Heart Team opted for conservative management of the LVD. Conclusion: GVD consists of the narrowing of the arterial lumen, due to the thickening and pathological remodeling of the tunica intima, due to the infiltration of mononuclear inflammatory cells. This condition has multiple possible etiologies, with immunological and non-immunological factors involved in the pathophysiology. The disease may result from a local and systemic inflammatory response initiated by alloantigen-dependent factors and non-immunological stress agents. The patient reported presented a clinical picture compatible with HFrEF due to decompensated GVD one month after infection by COVID-19 and change of the immunosuppressive regimen, without anatomopathological evidence of cellular or humoral rejection. In rare cases, there is evidence of accelerated progression of GVD from grade 0 (angiographically undetectable) to grade 3 (graft failure) in less than 4 months. Consequently, we believe that the systemic inflammatory response to SARS-Cov-2, with widespread cytokine production, direct myocytic damage, and vascular inflammation, may have played a key role in GVD progression. More studies with adequate methodology are needed to elucidate this potential association between GVD, myocardial damage and COVID-19 in HT recipients. 109816 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Spontaneous Coronary Dissection Angioplasty After Thrombolysis: Case Report MATHEUS RODRIGUES TEIXEIRA NETTO1, Eduardo Comazzeto dos Reis2, Selma Rodrigues Chaves2, Alessandra Teixeira de Oliveira2, Valter Correia de Lima2 (1) Universidade Federal de Ciencias da Saude de Porto Alegre; (2) Santa Casa de Misericordia de Porto Alegre Introduction: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction. The increase in its occurrence is related to the widespread use of coronary angiography in recent years. The etiology of SCAD is poorly understood. Its pathophysiology consists of separation of the arterial wall layers by intimal rupture or intraparietal hemorrhage, so that luminal narrowing and consequent coronary syndrome with elevation of biomarkers occur. Angiography shows the appearance of extraluminal contrast, multiple radiolucent lumens, and intraluminal filling defects. Conservative treatment is recommended, given the spontaneous healing of most lesions, while thrombolysis is contraindicated. Revascularization should be considered in case of ongoing ischemia, hemodynamic instability, arrhythmias or involvement of the left main coronary artery. Case Report: Female patient, 54 years old, hypertensive and diabetic, presented an episode of oppressive retrosternal pain. In the first evaluation, electrocardiogram showed a current from a subepicardial lesion in the lower-dorsal wall. At the origin hospital, loading doses of ASA and Clopidogrel were administered, followed by thrombolysis with Alteplase and Enoxaparin. Due to the absence of reperfusion criteria, she was referred for rescue catheterization, which showed a left main coronary artery (LMCA) with 98% stenosis and occlusion of the circumflex (LCX) and anterior descending (LAD) branches. After LMCA predilation, LMCA and LAD dissection were diagnosed. Implantation of 3 drug-eluting stents was performed in LMCA, LAD and LCX, with good angiographic results. Follow-up was given with Aspirin, Clopidogrel, Simvastatin and Metoprolol Succinate. Conclusion: The increase in the occurrence of SCAD brings with it the need for new studies to facilitate the understanding of how to manage it. Patients' inadvertent thrombolysis can worsen the condition and add to the need for new interventions. Therefore, whenever possible, all approaches should be based on the findings of coronary angiography. 109825 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Recurrent Gastrointestinal Bleeding in a Patient with Obstructive Asymmetric Septal Hypertrophic Cardiomyopathy, a Rare Form of Heyde Syndrome? ANA OLIVIA DANTAS1, KELSON KEMUEL CONFESSOR DE SOUSA2, THALINY BATISTA SARMENTO DE OLIVEIRA1, KELTON DANTAS PEREIRA2, FABIO MASTROCOLA2 (1) UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE; (2) HOSPITAL UNIVERSITARIO ONOFRE LOPES Introducao: Heyde's Syndrome (HS) is classically described as an association between aortic stenosis and gastrointestinal bleeding from angiodysplastic lesions. Acquired von Willebrand factor (fVW) deficiency is related to its pathogenesis and results from hemodynamic stress on the stenotic valve. It is believed that valve replacement reduces the risk of bleeding, with success in 80% of cases. Relato De Caso: Female patient, 60 years old, with chronic intestinal bleeding due to vascular ectasias in the gastrointestinal tract. She had clinical decompensation with major bleeding. Upper digestive endoscopy showed ectasia in the bulb and in the second and third duodenal portions without bleeding. Colonoscopy showed two angiectasia of the cecum and colon. On physical examination, aortic and mitral ejection systolic murmur was observed. Patient was unaware of previous heart disease. The ECG showed signs of left ventricular overload and the echocardiogram revealed asymmetric septal hypertrophy with left ventricular outflow tract (LVOT) obstruction - septum 26 mm and maximum systolic gradient 230 mmHg - and significant mitral regurgitation. Thus, the hypothesis of hypertrophic cardiomyopathy (HCM) with possible associated Heyde syndrome was raised, because, similarly to aortic stenosis, HCM in its obstructive asymmetric septal form could lead to the same mechanism of degradation of von Willebrand multimers of high molecular weight by the ADAMST13 enzyme due to the high shear stress generated by the interventricular septum in the LVOT. However, the dosage of Von Willebrand factor antigen (fVW) and ristocetin cofactor were normal. Conclusao: We describe a case of probable SH in a patient with bleeding from angiodysplasias in the gastrointestinal tract associated with hypertrophic cardiomyopathy. Despite the normality of the VWf antigen, this data does not invalidate a possible association between MCH and SH, since the isolated dosage of the von Willebrand factor antigen may be normal in patients with acquired von Willebrand disease. The patient was discharged after stabilization of intestinal bleeding and correction of anemia, using a beta-blocker with reduced LVOT gradient. If bleeding recurs, specific therapies can be tried to reduce the diameter of the interventricular septum, such as alcohol ablation, myectomy and radiofrequency ablation, aiming to correct the pathophysiological substrate responsible for gastrointestinal bleeding. 109833 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Neprilysin Inhibitor and Chagas Cardiomyopathy Improvement JOAO CLEITON MARTINS RODRIGUES2, Joao Cleiton Martins Rodrigues2, Talles Levi Pereira Nogueira2, Marcio Cesar Ribeiro Marvao3, Joao Maria Silva Rodrigues1 (1) Instituto Clinicardio; (2) Universidade Federal do Para (UFPA); (3) Instituto Evandro Chagas (IEC) Introduction: Chagas heart disease (ChHD) is caused by the protozoan Trypanossoma cruzi, was discovered in 1909 by Carlos Chagas and to this day is among the main endemic diseases of the Amazonic region. In the chronic phase the symptoms begin, resulting from the replication of protozoan amastigotes in myocytes, which causes mechanical cell's rupture and release of pro-inflammatory cytokines, resulting in loss of tissue function and fibrosis. From this there is the process of cardiac remodeling and heart failure due to chagas disease. In 2014, the PARADIGM-HF study reported that the use of sacubitril/valsartan (neprilysin inhibitor and angiotensin II receptor blocker) significantly reduced mortality and hospitalization for heart failure with reduced ejection fraction (EF) compared to the use of enalapril. Another research was conducted with ChHD with reduced EF doing sacubitril/valsartan treatment for 6 months, which showed an improvement in the functional classification of NYHA of patients, without significant improvement of the EF on doppler echocardiography (DEC). Description: A male patient M.J.P.S., 46 years old, 2 years ago sought clinical cardiology complaining of asthenia, epigastralgia, weight loss and insomnia. She had systemic arterial hypertension; heart failure (NYHA III); IgG indirect hemagglutination test and bioelisa reagents for chagas, cardiomegaly (+++) on chest x-ray PA; DEC showing diffuse involvement of an important degree in the left ventricle (LV), a image suggestive of thrombi at LV apex (approximately 20 x 21 mm2), EF of 29%, LV diastolic dimension of 69 mm (05/25/2020). After addicting sacubitril/valsartan in the treatment with carvedilol 6,25 mg/day, furosemide 20 mg/day, spironolactone 12,5 mg/day and sodic levothyroxine 50 mcg/day for approximately 6 months, a significant clinical improvement was noticed and DEC reported an enhancement in EF: preserved cardiac chambers, EF of 67%, diastolic dimension of LV of 53 mm (02/26/2022). Conclusion: Therefore, the sacubitril/valsartan, associated with carvedilol, spironolactone and furosemide improved the clinical outcome of a ChHD patient, reverting a condition of reduced EF. Then, that medication eschedule is effective as a treatment for chagas cardiomyopathy. 109841 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Holocardiac Involvement in a Patient with Adult-Onset Still Disease: A Case Report HENRIQUE KRICHENKO LEDRA1, Marcelo Vier Gambetta1, Franciani Rodrigues da Rocha1, Caroline de Oliveira Fischer Bacca1 (1) UNIDAVI - Centro Universitario para o Desenvolvimento do Alto Vale do Itajai Introducion: Adult-Onset Still's Disease is a rare condition, with a prevalence of 1-34 cases per million people, classified as a multigenic auto-inflammatory disorder, negatively affecting the patient's cardiovascular system through pericardial and myocardial damage mainly, considered an important risk factor for the development of cardiovascular diseases. Case Report: We reported ten years of evolution of a male patient, 30 years old, hospitalized due to presence of low blood pressure, jugular veins distention, and muffled heart sounds on cardiac auscultation, diagnosed with cardiac tamponade. A successful emergency pericardial drainage was performed. A month later he was hospitalized again because of chest pain, fever and dyspnea. Diagnosed as aortic valve endocarditis with important aortic regurgitation after echocardiological evaluation. Aortic valve replacement surgery with metallic valve implant was performed and the vegetation biopsy showed chronic inflammatory lesion with no infeccion associated. He was referred to outpatient evaluation with a rheumatologist doctor, who diagnosed him with Adult-Onset Still's Disease. Ten years after his first cardiovascular disability, the patient presented an important hemodynamic disturbance being hospitalized due to acute coronary syndrome because of the presence of thrombus in the descending and diagonal coronary arteries. He underwent successful balloon catheter angioplasty. Conclusion: Our hypothesis for the patient's cardiac involvement is based on the complex pathophysiology of the disease and it's possible complications. Pericarditis is well documented as a quite common Still's Disease complication. However the same does not apply to aortic valve vegetation since just a few reports bring the same association between those conditions. As far as we know, based on the literature, the occurrence of an intracoronary thrombus in a patient with Still's Disease is unprecedented and we consider the coagulation disorder the best pathophysiological hypothesis. 109856 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Role of Pulse Wave Velocity in the Individual Relevance of Individuals at High Cardiovascular Risk - Case Report DAVID FERREIRA DE LIMA DUARTE1, Maria Gabriela Pimenta dos Santos1, Julia Resende de Oliveira1, Gabriela Gama Zagni Jardim3, Lilian Soares da Costa4 (1) Universidade Estacio de Sa/IDOMED, Campus Citta e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (2) Universidade Estacio de Sa/IDOMED, Campus Citta e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (3) Universidade Estacio de Sa/IDOMED, Campus Citta e Presidente Vargas e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC; (4) Universidade Estacio de Sa/IDOMED, Campus Vista Carioca e Instituto Estadual de Cardiologia Aloysio de Castro/IECAC Introduction: The analysis of arterial stiffness through the measurement of pulse wave velocity (PWV) has been listed as one of the oscillometric parameters among the best predictors of cardiovascular (CV) risk, when compared to the use of traditional scores and brachial artery pressure analysis, which, although consecrated in the literature, have numerous limitations and complexity in their evaluation. Different studies have shown that increasing PWV doubles the risk of CV events, CV mortality and death from all causes. In individuals at high CV risk, regardless their vascular age, this correlation is not entirely clear and defined. Case Report: We report a cohort study of 163 individuals at high CV risk, object of a scientific initiation project at our institution. Male, 58 years old, white, hypertensive, obese, diabetic, submitted to percutaneous revascularization after acute coronary syndrome. Although with optimized prescription, it maintains irregular drug treatment and low adherence to lifestyle modifications. On examination, baseline blood pressure was 135 x 87 mmHg; FC 63 bpm; pulse pressure 46 mmHg. Vascular parameters showed central aortic pressure 120 mmHg and PWV 8.4 m/s, highlighting that the standards adopted for the medians adjusted for sex, age and presence of risk factor are 124 mmHg and 7.9 m/s, respectively. Remaining symptomatic in his outpatient risk stratification, he was submitted to a hemodynamic study, demonstrating severe coronary lesions (>80%) proximal in 4 vessels, and referred for surgical revascularization. Conclusion: The analysis of PWV has been important as an additive value in the functional analysis of individuals with coronary artery disease (CAD), in different suggestions of new risk models. In this context, we believe that arterial stiffness, in addition to the possible early manifestation of atherosclerosis, as established in national and international guidelines, can be a CV prognostic marker of individual relevance in high CV risk, as demonstrated in this case, where the presence of high PWV could even be an additional factor in the severity and extent of CAD. Whether this finding could predict a higher risk of CAD evolution, its therapeutic response or even infer prognosis, so far there are no answers, but we hope to be able to contribute to future analyzes with our cohort study. 109919 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Oral Facial Digital Syndrome: Report of a Patient Presenting an Atrioventricular Septal Defect Associated with Truncus Arteriosus GUILHERME RODRIGUES VIANA1, Guilherme Taioqui Fioruci1, Helena Guedes da Rocha1, Rafael Fabiano Machado Rosa1 (1) UNIVERSIDADE FEDERAL DE CIENCIAS DA SAUDE DE PORTO ALEGRE - UFCSPA Introduction: Oral facial digital syndrome (OFDS) represents a heterogeneous group of disorders of genetic cause, characterized by oral, facial and limb anomalies with or without associated visceral malformations. Our aim was to describe a patient diagnosed with OFDS presenting an atrioventricular septal defect (AVSD) associated with truncus arteriosus. Case Description: The pregnant, a 25-year-old woman, was in her third pregnancy and was referred at 20 weeks of pregnancy for presenting fetal ultrasound with description of congenital heart disease and polydactyly. The patient had a description of a previous pregnancy with a fetus with a history of hard palate and tongue abnormalities, polydactyly, syndactyly of fingers and toes, and suspected congenital heart disease. The child died on the first day of life. In the second trimester ultrasound performed in the current pregnancy at 20 weeks, the interatrial septum and the right ventricular outlet were not visualized. In addition, polydactyly of hands and feet was observed. Fetal echocardiography revealed a complete AVSD associated with pulmonary atresia. The fetal karyotype was normal (46, XY). The child was born by cesarean section at 38 weeks, weighing 3,200 g, with Apgar scores of 8 and 9. Physical examination revealed facial dysmorphia and tongue alteration indicative of the presence of hamartoma. There was also polydactyly of both hands, with the presence of 7 fingers, and syndactyly between the fourth and fifth fingers. There was also polydactyly of both feet, with partial syndactyly between the first two toes. Echocardiography performed shortly after birth revealed a complete type C AVSD and a ventriculo-atrial communication with a single right ventricular outflow valve. Computed angiotomography performed on the same day also showed the presence of a truncus arteriosus. Conclusion: The clinical findings herein observed, including the cardiac ones, are compatible with the OFDS type II diagnosis, also known as Mohr syndrome. Cardiac malformations, overall ASD and VSD, have been reported in patients with this subtype of OFDS. Nevertheless, the truncus arteriosus, as observed in our patient, is considered to be a quite rare finding. 109982 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Truncus Bovis, Abnormal Subclavian Artery and Aortic Aneurysm Without Genetic Inheritance: A Case Report CAIO RESENDE DA COSTA PAIVA1, Brenna Pinheiro Zuttion2, Pedro Pimentel Rocha Faria2, Veronica Homem de Carvalho e Silva1, Ana Carolina Bezerra Goes1 (1) Universidade de Brasilia; (2) Hospital Universitario de Brasilia Introduction: Among the most common congenital anomalies of the aortic arch, the retroesophageal right subclavian artery (RSA) (prevalence 0.5-1%) and Truncus bovis (prevalence 20-32%) stands out. These changes, mostly asymptomatic, are the result of defects in embryogenesis. Aortic aneurysm (AA) is an acquired anomaly and consists of a pathological dilation of this vessel. The case in question presents a patient in which these 3 alterations are present, without evidence of the presence of genetic syndrome (GS). Case Report: Patient, female, 59 years old, complaining of paresthesia in the right upper limb and neck pain for 3 days. He has a history of arterial hypertension, surgical repair of ascending AA and aortic trunk in 2012, with a Dacron tube installed, without valve replacement. In use of atenolol, ASA, metoprolol, olmersartan + amlodipine. Physical examination without changes. He was admitted to the Hospital de Base de Brasilia for investigation. An angiotomography of the chest and abdomen was performed, which showed type 1 thoracoabdominal AA, with a greater diameter of 75 mm in the descending segment, and intramural hematoma in this portion. Tortuous aorta except for the ascending portion, truncus bovis and retroesophageal ASD. Echocardiogram showed mild aortic insufficiency and coronary cineangiography showed stenosis of 60% in the anterior descending artery. SG were discarded. In view of this, we opted for a right carotid-subclavian bypass and, later, open surgery for thoracoabdominal AA, with cardiopulmonary bypass. Endovascular procedure was not performed due to impossibility due to aortic tortuosity. During the second operation, the patient evolved with myocardial infarction, refractory cardiogenic shock and death. Conclusion: Anatomical changes of the aorta and its branches in combination are uncommon and poorly reported. When present, they occur mainly in patients with some genetic syndrome. Although usually asymptomatic, the congenital changes seen can lead to symptoms resulting from local compression, aneurysmal degeneration or atherosclerosis, causing dysphagia and paresthesias. In these cases, surgical intervention is the option of choice as well as for AA depending on its diameter and complications. Due to the high aortic tortuosity, percutaneous treatment was discarded, opting for open surgical repair of the vessel. The large scale of the surgery and the patient's hemodynamic instability may have contributed to the outcome of the case. 110028 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Insidious Course of Infective Endocarditis in the Elderly: Considerations of the Diagnostic Challenge BRENO VINICIUS DIAS DE SOUZA1, Humberto Cabral de Oliveira Filho1, Heron Alves Vale1, Gerson Barbosa do Nascimento1 (1) Universidade Federal do Rio Grande do Norte (UFRN) Introduction: Infective endocarditis (IE) is characterized by inflammation of the endocardium, heart valves, or even an intracardiac device, such as pacemaker leads and prostheses. It is mainly by bacteria, and more, by fungi. Acute IE is usually caused by Staphylococcus aureus, and there is the subacute form, with slow evolution from weeks to months, with mild toxic, chronic fever and weight loss. A heart murmur may be present, as well as immunological and vascular phenomena. Case Report: Male patient, 80-years-old, retired, is supported in a referral hospital with a weight loss of 12 kilograms in 5 months. During that time, he had sporadic low-grade fever, which gave way to the use of simple analgesia, followed by sweating. Still, had severe arthritis, with limited range of motion due to pain. He had anemia in this temporal cut. The patient is hypertensive and has a history of exchange cancer treated with radiotherapy and valve surgery by aortic operation 10 years ago. It evolved with persistence of the joint, with characteristics of the lower limbs. Still, general condition, suffered with feverish brand, without compromising the general condition. On examination, calculated oral without teeth, with unsatisfactory hygiene. There was a murmur in the aortic focus. It presented three changes persistently, with an echocardiogram showing vegetation in the aortic valve. He received antibiotic therapy with ceftriaxone and oxacillin, evolving with improvement. Conclusions: The insidious course of the disease brought definitive treatment to establish a definitive diagnosis. The important echocardiogram image and the patient's predisposition to valvular heart disease were used to guide the management, but it is noticed that there is a limitation for some times, since fever is poorly measured and that immunological manifestations are often not confirmed. Therefore, attention should be paid to non-positive germs such as blood cultures, such as Coxiella burnetii and fungi, which have a prolonged course. 111770 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES 3D Printing in Mitral Stenosis' Surgical Planning - Case Report MATEUS DOS SANTOS BANDEIRA1, Ana Luisa Guedes de Franca-e-Silva2, Maria Luiza Novaes de Souza1, Eduarda Correa Maia1, Claudio Tinoco Mesquita1 (1) Universidade Federal Fluminense - UFF; (2) Universidade Federal de Goias - UFG Introduction: 3D printing is revolutionizing medical imaging. In cardiology, 3D printing is increasingly used by surgeons and health professionals, such as cardiovascular surgeons, in procedures with cardiac involvement, including mitral stenosis. Description: A 57-year-old female patient reported dyspnea on moderate exertion, which began gradually and progressed to progressive worsening, being associated with orthopnea. She complained of chest discomfort. Patient had a history of interatrial communication corrected in 1987 associated with cleft repair of the anterior mitral leaflet, severe mitral regurgitation, tricuspid regurgitation, permanent atrial fibrillation, in addition to having systemic lupus erythematosus. A transthoracic echocardiogram demonstrated a cleft of the anterior leaflet of the mitral valve associated with severe regurgitation. 3D impression of the heart was performed with atrial and ventricular sections through preoperative CT images. The objective was to better understand the extent of the disease and assist in surgical planning, seeking to understand the potential benefit of the surgical approach. After 3D printing the selected approach was a median sternotomy with resection of the leaflets and implantation of a metallic mitral valvar prosthesis (numb er 3), associated with closure of the interatrial septum with a bovine pericardium patch and tricuspid annuloplasty with a number 28 ring. Unfortunately, patient died in 22nd postoperative day due to central venous catheter infection. Conclusion: We describe the use of 3D printing to anticipate a realistic cardiac surgery, to guarantee a safe surgery, as well as to promote a reduction in the duration of the surgery. Due to the size of the IAC dimension, it is possible to allow a joint visualization of the defect size in the middle of a wide 3D impression of the target organ. This case reinforces the future promise of modeling for surgical planning purposes, in addition to the future of such modeling for education. 110385 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Clinical-Conservative Treatment Strategy After Coronary Dissection at the End of Pregnancy GABRIEL ALVES MENESES1, Taua Richel Belchior da Costa1, Kaio Saramago Mendonca1, Marcela Souza Carneiro1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia Introduction: Usually, the main causes of maternal mortality related or aggravated by pregnancy are hypertension, hemorrhage, puerperal infections, and miscarriage. However, other cardiovascular causes have contributed to increased pregnancy-related morbidity and mortality. In this scenario, arterial dissections (mainly of the aorta and coronary arteries) have an important role and also different therapeutic possibilities. Case Report: Second-time pregnant, 34 years old, 35 weeks and 5 days, obese, without other comorbidities or gestational complications, presented with intense precordialgia with irradiation to the dorsum and left upper limb, lasting more than one hour after a light walk. Referred to the tertiary service with positive myocardial injury markers, dynamic T-wave in anterior wall on electrocardiogram (ECG), but without ST segment depression. Started propedeutics of Non-ST Segment Elevation Myocardial Infarction (NSTEMI). The hypothesis of coronary dissection was considered and initial drug treatment was chosen. Patient remained hospitalized and underwent cinecoronariography at 37 weeks of gestation, which showed dissection of the left main coronary artery involving the anterior descending and circumflex arteries with TIMI III coronary flow. Clinical treatment was maintained and caesarean section was performed at 38 weeks under general anesthesia. She presented, in the puerperium, a new presentation of chest pain, with dynamic ECG, without enzymatic elevation. Coronary angiography was repeated and improvement of the angiographic aspect of the coronary dissection was identified, and the expectant management was maintained. The binomial was discharged from hospital in good general condition and remained well for the last 6 months. Conclusion: Due to hormonal changes and the hyperdynamic state, pregnancy alone increases the risk of acute myocardial infarction (AMI). Commonly, because we deal with young women, atherosclerotic diseases are not the main cause of AMI during pregnancy, but arterial dissections, which normally receive a differentiated therapeutic strategy. In addition, these dissections are associated with the occurrence of death or a reduction in maternal ejection fraction, which is directly related to maternal-fetal complications. 110398 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT A Novel Genetic BAG3 Gene Variant Associated with Peripartum Cardiomyopathy and Family History of Sudden Death ANTONIO PEDRO LIMA COSTA PEREIRA1, Giovanna Lucieri Alonso Costa1, Ana Paula Cassetta dos Santos Nucera1, Maria Angelica de Faria Domingues de Lima2, Fabio de Souza1 (1) Universidade Federal do Estado do Rio de Janeiro (UNIRIO); (2) Hospital Universitario Gaffree e Guinle (HUGG) Introduction: Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). The BAG3 gene encodes a protein that is highly expressed in cardiac muscle and is involved in the anti-apoptosis effect. BAG3 pathogenic variant is associated with autosomal dominant DCM and has been reported in PPCM and in families undergoing sudden death. Case Description: A 36-year-old black woman presented to the emergency department with palpitations while breastfeeding her 2-week-old daughter. She denied any other symptoms. Medical history included diabetes mellitus type 1 and preeclampsia. Electrocardiogram (ECG) exhibited ST segment deviation and inverted T-waves in the precordial leads. Echocardiogram revealed left ventricular enlargement with diffuse hypokinesis. There were no records of raised troponin levels. Weeks later, magnetic resonance (MRI) showed reduced left ventricular ejection fraction (29%) and late gadolinium enhancement detecting presence of fibrosis. In the patient's family history, her father, brother and paternal half-brother died suddenly at 42, 28, and 26 years old, respectively. During a further investigation, a cardiomyopathy gene panel identified a heterozygous BAG3 pathogenic variant with a cytosine deletion at position 824 (c.824del). The result was consistent with the diagnosis of, BAG3-related conditions, including autosomal dominant DCM, and this variant has not been reported in the literature. Regarding her medical history, coronary artery disease was ruled out, and her coronary calcium score was 0. It was considered to place an implantable cardioverter-defibrillator, but myocardial findings on MRI were completely reverted as were ECG and echocardiogram repeated after three years. At present, the patient has no complaints. She is under clinical cardiology care, and genetic counseling will be provided for her relatives. Conclusion: This case report highlights a rare occurrence of peripartum cardiomyopathy in a patient in which a novel pathogenic variant in the BAG3 gene was identified and related to a strong family history of sudden death. 110547 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Electrocardiographic Clues in a Rare Case of Hereditary Transthyretin Cardiac Amyloidosis ANA GABRIELLA MEDEIROS1, Caroline Bittar Braune2, Marcio Aloysio Freitas Siqueira Junior3, Ana Paula Cassetta dos Santos Nucera1, Fabio de Souza1 (1) Universidade Federal do Estado do Rio de Janeiro; (2) Hospital Universitario Gaffree e Guinle; (3) Hospital Sao Lucas Introduction: Transthyretin cardiac amyloidosis (TTR-CA) is currently being discussed as a possible underlying cause of heart failure with preserved ejection fraction (HFpEF). Despite advances in cardiac imaging, monitoring electrocardiograms (ECGs) remains imperative for reducing TTR-CA misdiagnoses. Case Presentation: A 78-year-old black man presented with breathlessness and progressive exercise intolerance. He had a medical history of mild hypertension controlled with losartan 50 mg once daily. Physical examination showed blood pressure of 120/80 mmHg, heart rate 66 bpm, and no edema or pulmonary congestion. Initial ECG was described as nonspecific and indicated a possible previous infarction. Two-dimensional echocardiogram (2D-Echo) revealed ejection fraction 55%, left ventricular (LV) hypertrophy (septum 13 mm), diastolic dysfunction grade 3, and no segmental changes. HFpEF was considered and a loop diuretic was prescribed. In fact, ECG demonstrated sinus rhythm, PR interval 220 ms, narrow QRS complex with left axis deviation, disproportional amplitude of QRS complex related to assumed LV hypertrophy by 2D-Echo, and absence of R-wave progression in the anterior leads, which were interpreted as a pseudo-infarction. A reduced global longitudinal strain (-13%) measurement was obtained with an "apical sparing" pattern. Scintigraphy with technetium pyrophosphate confirmed TTR-CA (Perugini grading scale = 3). Genetic testing detected a pathogenic variant in TTR gene (genotype V142I) in which cardiac involvement is predominant. Conclusion: This report highlights ECG findings in a case of TTR-CA. Pseudo-infarction pattern and/or discordant amplitude of QRS compared to LV hypertrophy can be subtle clues indicating TTR-CA. Attention to the ECG is crucial to enable this challenging diagnosis. 110896 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR PHARMACOLOGY Marfan Syndrome: Importance of Drugs that Reduce Hemodynamic Stress in the Prevention of Aortic Aneurysm GEORGIA MARQUES JARDIM 1, Rafael Fabiano Machado Rosa1, Marco Antonio Vinciprova Dall Agnese1, Rafaella Alessio Naibo2, Alexandre Perin Decol1 (1) Universidade Federal de Ciencias da Saude de Porto ; (2) Universidade Federal do Rio Grande do Sul - UFRGS Introduction: Marfan syndrome (MS), is a systemic connective tissue disorder with a high degree of clinical variability. The main manifestations consist of alterations involving the ocular, skeletal and cardiovascular systems. The short-term segment of a patient with MS, emphasize the importance of using propranolol in preventing the development of aortic aneurysm. Case Report: A 13 years old female patient who had a paternal family history of cardiopathy in a cousin and grandparents. Both grandparents passed away due to heart disease. Patient full-term newborn, with 2,9 kg weight and 51 cm of height. The patient was forwarded for investigation of fainting and right facial paralysis within one week of evolution. The examination identified oblique palpebral slits, low ear implantation, important scoliosis, arachnodactyly in both hands and feet, joint hypermobility and Marfan's habitus. In cardiac auscultation, was identified a systolic murmur 3+/6+. The electrocardiogram had a precordial repolarization alteration. The echocardiography showed normal systolic biventricular function, mild left ventricular enlargement, systolic prolapse of the mitral valve in both leaflets, moderate valve regurgitation, ectasia in the region of the sinuses of Valsalva, aortics and ascending aorta, and aortic regurgitation. Therefore, she started using propranolol 10 mg, 3 times a day. During his echocardiographic follow-up, no dilatation or appearance of aortic aneurysm was observed, in the period of three years. The spine radiography showed marked dextroconvex dorsal and left convex lumbar scoliosis. The ophthalmologic evaluation revealed bilateral iridodonesis, Bell's palsy, alternating exotropia, and superior lens subluxation. All these findings led to the diagnosis of Marfan syndrome. Conclusions: Drugs that decrease hemodynamic stress on the aortic wall, such as the use of b-blockers or angiotensin receptor blockers, are usually initiated at diagnosis or upon evidence of significant and/or progressive aortic dilatation in patients with MS. This therapy aims to prevent the development of aneurysms and the possible occurrence of aortic dissection, an important cause of death among these patients. 110607 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Diabetic Embryopathy and its Relation with Congenital Heart Diseases GRASIELE DO AMARAL MARTINS1, Carolina Guimaraes Herzog1, Emanuella Lara Tarzo de Medina Coeli1, Rafaella Alessio Naibo2, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (2) Universidade Federal do Rio Grande do Sul Introduction: Insulin-dependent diabetes mellitus (DM1) can lead to the presence of a spectrum of malformations known as diabetic embryopathy. The aim of this report was to discuss the findings of a fetus whose gestation course was characterized by diabetic embryopathy, highlighting its relationship with congenital heart disease (CHD). Case Description: A 24-year-old, primiparous pregnant woman with a past medical history of DM1. Fetal ultrasound was performed outside the hospital at 22 weeks of pregnancy, the report described holoprosencephaly, congenital heart disease and single umbilical artery. Fetal echocardiography showed dextrocardia; double inflow tract atrioventricular connection to the left ventricle; single outflow tract ventriculoarterial connection and truncus arteriosus. Morphological ultrasound also showed increased amniotic fluid, single umbilical artery, and dilation of the third and lateral ventricles. The complementary examination also showed no visualization of the right kidney, the left kidney was small, and an abnormality was observed in the fetal spine. Fetal magnetic resonance imaging confirmed the finding of supratentorial hydrocephalus, in addition to the other malformations described on the ultrasound. The fetal karyotype was normal. The child was born by c-section at 33 weeks gestation, with a head circumference of 45 cm and Apgar scores of 3/7. Abdominal ultrasound showed that the right kidney was pelvic and the left kidney was multicystic dysplastic. Spinal x-ray showed hemivertebrae and butterfly vertebrae. Conclusion: In the literature, there are reports that there is a relationship between diabetic embryopathy and fetal findings of VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association, as observed in the present case report. CHD are part of the clinical spectrum of both conditions, with emphasis on those of the conotruncal type, i.e., involving the outflow tracts of the heart, as in the case of truncus arteriosus. 110855 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Takotsubo Syndrome Secondary to Catsaridaphobia MIKE VINICIUS CANTO DE ANDRADE1, Danielle Campos de Almeida1, Gabriel Alves Meneses1, Fabio Vieira Fernandes1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia Introduction: The cardiologic syndrome called "Takotsubo", also called broken heart syndrome, is a type of stress-induced cardiomyopathy characterized by transient apical bulging and left ventricular dysfunction. The clinical picture usually mimics the same one of an acute myocardial infarction. In the absence of significant coronary obstruction, it courses with transient left ventricular dysfunction (usually apical). Characteristically, the clinical picture is preceded by intense emotional and/or physical stress. There is little data in the literature on fear or phobia reactions to insects or other potentially repulsive animals that lead to this condition. Case Report: Female patient, 58 years old, previously healthy, asymptomatic. Started with typical intense and tight chest pain for 2 hours. She describes similar, less intense episodes in the 2 days prior to arrival at the hospital. Given a history of catsaridaphobia, she reported significant acute stress after contact with a cockroach 12 hours before the initial episode. Physical examination without changes. Electrocardiogram: sinus rhythm, anteroseptal inactive electrical zone and slight ST-segment elevation in the anterior wall. There were typical enzymatic alterations. Cardiac catheterization did not identify coronary stenoses, but a pattern of left ventricular apical akinesia characteristic of Takotsubo Syndrome. Echocardiogram confirmed apical akinesia. Cardiac Magnetic Nuclear Resonance, 5 days later, showed basal anterior myocardial edema and medial septum, without fibrosis and with improvement in ventricular function. The patient had a good clinical evolution and was discharged from the hospital on the 7th day, with normal global contractile function. She is asymptomatic one year after the initial event. Conclusion: The reported clinical picture simulated an acute myocardial infarction, once absence of coronary obstruction was established, along with apical systolic dysfunction of the left ventricle and hyperkinesia of the basal portions. Transient acute ventricular dysfunction was clearly related to intense emotional stress, fulfilling current criteria for the diagnosis of stress-induced cardiomyopathy syndrome. The inducing stress of the condition was physical contact with an insect to which he has a phobia, whose occurrence may be the stressor mechanism for a part of the cases that develop Takotsubo syndrome. 110928 Modality: E-Poster Scientific Initiation - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM The Need of Prompt Diagnosis of Mis-C to Prevent Cardiac Sequelae: A Case Report of a 2-Year-Old Patient ALINE PETRACCO PETZOLD1, Bibiana Liberman Thome1, Fernanda Serratte Warlet2, Larissa Arruda Ferreira2, Andrea Mabilde Petracco2 (1) Pontificia Universidade Catolica do Rio Grande do Sul; (2) Hospital Materno Infantil Presidente Vargas Introduction: Kawasaki disease (KD) is one of the most common primary systemic vasculitis in childhood, being the main cause of acquired heart disease in children. Throughout the COVID-19 pandemic, cases with manifestations similar to KD were reported, being classified as Multisystem Inflammatory Syndrome (MIS-C) following SARS-CoV-2 infection. Most findings for the disease are nonspecific, such as high, persistent fever, and inflammatory findings without an infectious explanation. Despite usually being a self-limited disease, prompt diagnosis and management are fundamental to prevent cardiac sequelae, since coronary artery aneurysms occur in 25% of untreated or poorly treated cases. Case Report: Male, 2-year-old patient, had contact with SARS-CoV-2 in January 2022. Admitted to the emergency for persistent fever for 20 days, with peaks every 2 days, associated with greenish coryza, rhinorrhea and eye discharge. A week before, was treated for otitis media with 3 doses of ceftriaxone, having momentary improvement, but further worsening. In the hospital, he presented fever, upper airway infection symptoms, conjunctival hyperemia with bilateral discharge, exsudate in oroscopy, opacity in the right tympanic membrane, hemoglobin of 10.2, and negative hemocultures and PCR for COVID-19. Echocardiography revealed patent foramen ovale and dilation of the anterior descending coronary artery, raising the hypothesis of post-COVID-19 MIS-C. The patient was started on acetilsalicylic acid (AAS) and methylprednisolone, persisting with mild fever. Since it was not available previously, he received intravenous immunoglobulin (IVIg) only 12 days after the diagnosis, showing clinical improvement. He was discharged with AAS and a scheduled echocardiogram in 15 days. Conclusion: Since the findings for MIS-C are nonspecific and, in the absence of specific tests for the disease, its diagnosis relies on clinical manifestations, it is important to maintain a high degree of suspicion for the syndrome. Children with unremitting fever, an epidemiologic link to SARS-CoV-2 and suggestive clinical symptoms should be thoroughly evaluated. Prompt recognition and management are crucial to control the hyperinflammatory state and prevent severe organ dysfunction and potentially fatal complications, such as coronary aneurysms. Supportive care, IVIg, corticosteroids, biological immunomodulators, antiplatelet therapy, and prophylatic anticoagulation are key in the management of these childre. 110997 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR INTENSIVE CARE/CARDIOVASCULAR EMERGENCIES Acute Aortic Root Dissection in Two Patients with Marfan Syndrome LUANA DIAS XAVIER1, Joao Paulo Dias Costa1, Julia Sousa Diniz1, Beatriz Luduvice Soares1, Emerson De Santana Santos1 (1) Universidade Federal de Sergipe Introduction: Aortic root dilatation/dissection is one of the cardinal features of Marfan syndrome (MS), a heritable disorder of the fibrillin 1 gene (FBN1), which leads to a systemic disorder of connective tissue, with a high degree of clinical variability manifestations and involves the ocular, skeletal, and cardiovascular systems. Abnormalities of the aortic wall are quite frequent in this population, causing progressive aortic dilatation, thus increasing the risk of acute aortic dissection. Case reports: Two adult patients were referred from cardiothoracic surgery service to cardiogenetics evaluation after recovering from the successful intervention for acute aortic root dissection. Both patients were middle-aged males, not related, who fulfilled the Ghent criteria for MS. Patient 1 had no other affected member in the family and an FBN1 pathogenic variant was found. Patient 2 had an affected son and no molecular exam was performed. Other clinical data are summarized in the table. Conclusion: Although other MS typical features were previously present, the two reported cases had the diagnosis confirmed only after cardiogenetics evaluation. The delay in diagnosis is quite harmful once, with proper management, the life expectancy of someone with Marfan syndrome approximates that of the general population. Genetic counseling was provided for both families and the patients have been followed by a multidisciplinary team. 111085 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY 8 Years Old Patient with Cyanotic Congenital Heart Disease and Upper Extremity Deep Vein Thrombosis: A Case Report LUISA RIGO LISE1, Luiza Fernandes Xavier1, Sabrina Comin Bizotto1, Julia Helena Wegner1, Adriana Chassot Bresolin2 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS); (2) Universidade Estadual do Oeste do Parana Introduction: The Complex Cyanotic Congenital Heart Disease is a deformation in the embryonic development of cardiac structures, causing an altered blood flow which may result in failures in the development of the circulatory system and systemic arterial oxygen desaturation. Its prevalence is aproximadely 1.45 per 1000 children. Description: Female, 8 years old, diagnosed in intrauterine life by fetal echocardiography with situs inversus and cyanotic congenital heart disease. Father, 35 years old, and mother, 24 years old, both healthy with family history of second cousin with aortic coarctation. Full-term cesarean delivery with premature placental detachment. The echocardiography postnatal showed: situs inversus with levocardia; single left ventricle; hypoplastic right ventricle with double-outlet right ventricle; transposition of great arteries; total anomalous pulmonary venous connection (TAPVC); ostium primum; interventricular communication. At 1 year and 5 months, Glenn procedure and correction of TAPVC were performed without complications. At 6 years old, she developed upper extremity deep vein thrombosis, involving brachiocephalic, internal jugular and right subclavian. A computed tomography showed agenesis of inferior vena cava and overload of azygos-hemiazygos system that drains to right brachiocephalic vein. The patient progressed with more cyanosis, hepatomegaly and increased intensity of second sound and initiated Furosemide and Enoxaparin. Carvedilol, Enalapril, Dildenafil and Spironolactone were associated because of worsening signs of heart failure. 6 months after this episode, Enoxaparin was changed by Warfarin. Currently, at 8 years and 3 months, thrombosis of brachiocephalic and right subclavian veins are already resolved and thrombosis of internal jugular vein is in regression. In addition, she has diastolic dysfunction of ventricles, moderate insufficiency of atrioventricular valve and, due to the difficulty of controlling anticoagulation, warfarin was suspended and dabigatran was prescribed. Conclusion: In this case, the association between anomalous venous return, blood hyperviscosity and hyperglobulinemia due to chronic hypoxia is observed as the cause of thromboembolism. Besides that, the Fontan Surgery was contraindicated due to agenesis of inferior vena. Therefore, early diagnosis, through fetal echocardiography and a careful medical follow-up, guarantees a better prognosis and lower morbidity and mortality in cases like this. 111168 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Atypical Presentation of Carcinoid Sindrom with Severe Tricuspid Regurgitation LEONARDO PESSANHA CORDEIRO1, Juliana Fraga Soares1, Mellyssa Dias de Oliveira2, Pedro Hissa Monteiro1, Daniel J.M. Medeiros Lima1 (1) Faculdade de Medicina de Campos - FMC; (2) Centro Universitario Redentor - UniRedentor Carcinoid tumors are tumors that originate most commonly in the enterochromaffin cells of the gastrointestinal tract, especially in the small intestine. In the presence of liver metastases or a production that exceeds the metabolism capacity, substances such as serotonin fall directly into the systemic circulation, causing the carcinoid syndrome. The prognosis is worse in patients with carcinoid syndrome and carcinoid heart. Here we report an atypical presentation of carcinoid syndrome with early involvement of the right heart chambers, without flushing or diarrhea: a 49-year-old woman with complaints of nausea and vomiting with one-month evolution, lower limb edema associated with increased abdominal volume, and an involuntary weight loss of 10% in 6 months. Physical examination showed important ascites with mobile dullness and positive Piparote sign, bilateral lower limb edema 2+/4, pathological jugular swelling, and systolic murmur in tricuspid focus 2+/6 with reinforcement after the Riveiro Carvalho maneuver. A magnetic resonance imaging revealed numerous hypervascular nodular lesions, suggestive of metastasis. A liver biopsy, immunohistochemistry, scintigraphy with a somatostatin analogue (Octreoscan), Chromogranin A and 5-hydroxy indole acetic acid levels were compatible with carcinoid syndrome resulting from a carcinoid tumor of the gastrointestinal tract. The echocardiogram showed an increase in the volume of the right atrium and ventricle with severe tricuspid regurgitation, the valve was thickened, with failure to coaptation of its leaflets. The main therapy for the carcinoid heart currently used is the somatostatin analogues. Surgical intervention as valvar replacement is also a possibility for a sectioned patient who is more likely to benefit from an invasive approach. 111275 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOLOGY OF SPORTS, EXERCISE, ERGOMETRY AND CARDIOVASCULAR REHABILITATION Post - COVID-19 Cardiovascular Rehabilitation - Case Report LUISA DE LAMARE DOS SANTOS PAULA 1, Gustavo Henrique de Oliveira1, Thiago Honorio Dutra da Silva2, Jaqueline Lyrio Bermudes Okawa2, Rogerio Toshiro Passos Okawa1 (1) Universidade Estadual de Maringa; (2) Avancor Cardiologia R.A.F., male, 35 years old, businessman, born in Japura-Parana, from Santa Monica-Parana. Patient had a Covid-19 infection in March 2021, being admitted to an intensive care unit, for supplemental oxygen therapy in a high-flow mask. Thorax tomography showed 75% of pulmonary involvement. He had elevation of troponin and BNP during hospitalization. He was discharged with dyspnea on exertion, NYHA functional class II, being evaluated and requested complementary exams 30 days after hospital discharge, with echocardiogram with left ventricular ejection fraction with slight reduction: 42%, and reduced global longitudinal strain: - 12%. Cardiopulmonary stress test demonstrated Vo2: 24 mL/kg*min (72% of predicted), aerobic threshold 38% of predicted, with drop in oxygen pulse. He was medicated with Sacubitril/valsartan 49/51 mg every 12 hours, Bisoprolol 2.5 mg daily and Dapagliflozin 10 mg daily. Referred to cardiovascular rehabilitation, with 3 sessions per week, lasting 1 hour in each session. After 3 months of cardiovascular rehabilitation and pharmacological treatment, the symptoms improved, with a functional class I NYHA. The echocardiogram was repeated with improvement in left ventricular ejection fraction: 52%, improvement in global longitudinal strain: -16%, and improvement in ergospirometry parameters: Vo2: 37 mL/kg*min (90% of predicted), aerobic threshold 55% of predicted, oxygen pulse normalization. The present case report demonstrates a post-covid myocarditis, with left ventricular systolic dysfunction and the importance of pharmacological treatment with cardiovascular rehabilitation in this case. 111281 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY POF as a Cause of Cryptogenic Ischemic Stroke in Elderly MARIA GABRIELA PERERA1, Eveny Moraes Prola1, Helena Fussiger1 (1) Universidade Feevale Introduction: Ischemic stroke (IS) is the leading cause of morbidity in the world. In 30-40% of cases, TOAST classification is from a cryptogenic etiology. In these cases, the patent oval foramen (POF) may be the etiologic agent through paradoxical embolism. In young patients (18-60 years), 10% of cases are associated with POF, in elderly, however, attributing the cause of the vascular event to FOP is still a major challenge. Case: A previously healthy 70-year-old male presented with sudden onset of vertigo, nausea and vomiting, ataxia, hypoesthesia, and paresthesia of the left hemiface and left upper limb, lasting for 2 hours. His MRI scan showed no acute changes; only malacia in the left cerebellar hemisphere, but previous clinical history of focal neurological deficits. Then he was diagnosed with a transient ischemic attack (TIA). In the etiological investigation, transcranial Doppler identified passage of >20 HITs at rest, and after Valsalva maneuver >60 HITs, within the first 10 seconds of the infusion, considered a large shunt. Transesophageal echocardiography revealed interatrial septal aneurysm and POF with passage of a large amount of bubbles during the Valsalva maneuver. The rest of the investigation (with cervical Doppler, ECG, and laboratory tests) showed no changes that would justify the cerebral vascular event. RoPE score was 3 and PASCAL classified as a vascular event possibly related to POF. Treatment with Apixaban was initiated and a percutaneous endovascular closure procedure was performed for correction of POF. Discussion: The association of POF with IS in young is already established. However, in case of elderly with cryptogenic event, especially in cases of TIA, where we don't have the imaging to indicate event suggestive of embolism, the connection becomes even more difficult. According to a systematic review of 2021, in patients with possible PASCAL classification, the absolute risk of ischemia recurrence in 2 years was 3.6 and 1.5 for those treated conservatively versus invasively, respectively. But the data are valid mainly for patients between 8-60 years. In elderly, more studies are needed to inform the therapeutic decision, which is still a challenge today. References: Saver JL, et al. POF closure versus medical therapy for cryptogenic IS: topical review. 2018. Kent DM, et al. Heterogeneity of treatment effects in an analysis of pooled individual patient data from randomized trials of device closure of POF after stroke. JAMA. 2021. 111282 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Acute Reversible Aortic Insufficiency During Percutaneous Coronary Angioplasty: A Rare Mechanical Complication ARNOBIO ANGELO DE MARIZ NETO1, Carolline Araujo2, Luan Martins de Sousa3, Mateus Macena Correia de Lima3, Arnobio A. Mariz Jr3 (1) UNINASSAU; (2) Faculdade de Medicina de Olinda - FMO; (3) Pronto Socorro Cardiologico Universitario de Pernambuco Prof. Luiz Tavares, PROCAPE/UPE Percutaneous coronary angioplasty in patients with non-ST elevation acute myocardial infarction (NSTEMI) is a relatively common procedure and severe acute aortic regurgitation is a rare complication. We report a case of acute reversible aortic regurgitation during percutaneous coronary angioplasty in a 67-year-old woman, diabetic and hypertensive, with chronic coronary atheromatous disease who was admitted to hospital with NSTEMI. Subocclusive lesion in the circumflex artery and severe lesion in the anterior descending artery were evidenced in cardiac catheterization. During anterior descending angioplasty, a slowing of the flow through the vessel was observed , proceeded with the direct implantation of a drug-eluting stent with Sirolimus. At this moment, the patient developed oppressive chest pain, radiating to the upper limbs, profuse sweating, vomiting, sinus bradycardia and cardiogenic shock (BP = 64 x 42 mmHg). The images revealed significant acute aortic insufficiency caused by the guiding catheter (Amplatz AL1) and reversed with the removal of the catheter. A new angiographic control revealed stents implanted with good results and a final TIMI III arterial flow . No dissection of the left main coronary artery was observed. Acute aortic regurgitation caused by coronary catheterization can be avoided through careful handling of the catheter, especially in challenging scenarios or in patients with an anomalous coronary origin. 111785 Modality: E-Poster Scientific Initiation - Case Report Category: HYPERTENSION/RENAL DENERVATION Preeclampsia and its Association with Patau Syndrome PEDRO HENRIQUE TORRES TIETZ1, Lais Bettoni1, Carolina Feijo Bombana1, Guilherme Rodrigues Viana1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) Introduction: Trisomy 13 or Patau Syndrome (PS) is considered a chromosomal disease characterized by multiple malformations and a limited prognosis. The following reports indicate that pregnancies with trisomy 13 have higher risk of developing preeclampsia. This association is related to the placental abnormalities which are frequently found in pregnancies of PS fetuses, including reduced placental volume and vascularization and placental mesenchymal dysplasia. Case Description: The first case reported a 30-year-old pregnant woman in her fifth pregnancy. She had a past medical history of one pregnancy loss. She was monitored by prenatal care and at the final stage of pregnancy she developed preeclampsia. She wasn't submitted to fetal ultrasound at anytime of the pregnancy. The child was born prematurely at 36 weeks, weighing 2550 grams, by cesarean section. The Apgar score was 3/9. On examination, multiple alterations were observed, which included microcephaly, aplasia cutis on the scalp, cleft lip, micrognathia and hypertonia. Her karyotype indicated mosaic PS (47, XX, +13/46, XX). The child evolved with clinical worsening and died at 26 days of life. The pregnant woman in case 2 was 27 years old and in her second pregnancy. The pregnancy was accompanied by prenatal care, and it evolved with an episode of vaginal bleeding at 13 weeks. In addition, there was a description of an episode of urinary tract infection and preeclampsia. Due to the latter, the child was born by induced vaginal delivery. The other ultrasound exams performed during pregnancy were described as normal. The child was born at 37 weeks' gestation, weighing 2445 grams and with Apgar scores of 6 and 8. In her examination, there were alterations such as microcephaly, trigonocephaly, aplasia cutis on the scalp, microphthalmia, micrognathia, micropenis, empty scrotum, and polydactyly of hands and feet. The karyotype was compatible with PS (47, XY, +13). The child died at 12 days old. Conclusion: Pregnant women with PS fetuses have a higher risk of developing preeclampsia, considered one of the main causes of maternal death during pregnancy. This may have important implications for the management and prognosis of these patients. 111333 Modality: E-Poster Scientific Initiation - Case Report Category: HYPERTENSION/RENAL DENERVATION Secondary Arterial Hypertension by Aldosterone Producing Adenoma: A Case Report IUGO ALVES DE SOUSA1, Filipe Batista de Brito3, Gabriela Menezes Goncalves de Brito2, Matheus Araujo de Medeiros1, Renner Cassio Nunes de Lucena1 (1) Universidade Federal do Rio Grande do Norte; (2) Universidade Tiradentes-SE; (3) Hospital de Cirurgia-SE Introduction: Adenomas are among the causes of increased aldosterone production by the adrenal gland. The prevalence in hypertensive patients varies from 3% to 22%, being higher in hypertensive patients who are difficult to control. In general, patients have stage 2 or 3 hypertension, which may be refractory to treatment. Currently, it is known that the prevalence of hypokalemia in primary hyperaldosteronism varies from 9% to 37% of cases. In the diagnosis of this condition, the differentiation between hyperplasia and adenoma is essential for proper treatment. From a clinical and laboratory point of view, patients with adenoma are, in general, younger, have more severe hypokalemia and higher aldosterone concentrations (> 25 ng/dl). Case Report: Female, 32 years old, asymptomatic, with grade III arterial hypertension despite the use of three antihypertensive drugs of different classes. When performing abdominal ultrasound for ovarian evaluation, a random adenoma was observed in the left adrenal measuring approximately 3.5 x 2.9 x 2.5 cm with a volume of 19.2 cm2, which was later confirmed by on total abdominal tomography. Aldosterone and renin levels were then requested and the results showed an aldosterone overproduction (37.2 ng/dL) not accompanied by a renin suppression (4.7 uIU/mL). A potassium dosage was also requested, which allowed the identification of hypokalemia (2.2 mEq/L). After confirmation, the patient followed for evaluation of cardiovascular alterations. Echocardiography showed eccentric left ventricular hypertrophy with mild mitral regurgitation, which suggests a functional impairment of the heart. Then, the patient was referred for unilateral adrenalectomy. Conclusion: The case in question presents the diagnosis of a unilateral aldosterone-producing adenoma, in a young woman with a history of resistant arterial hypertension, accidentally identified in an imaging exam. The report aims to alert professionals about the need to screen this cause of secondary hypertension in all hypertensive patients with spontaneous or diuretic-induced hypokalemia and in hypertensive patients resistant to usual treatments, so that the disease is diagnosed early and treated according to guidelines. 111441 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIAC ARRHYTHMIAS/ELECTROPHYSIOLOGY/ELECTROCARDIOGRAPHY Bayes Syndrome in an Infant: Case Report with Atrial Fibrillation Associated with Bachmann Bundle Block and Tachycardiomyopathy ANTONIO MAYCON DA SILVA SOUSA1, Carlos Eduardo Batista de Lima2, Patryck Araujo Dantas da Silva1, Marcelo Madeira Pinheiro Silva2 (1) Universidade Federal do Piaui (UFPI); (2) Hospital Universitario da Universidade Federal do Piaui - (HU-UFPI). Introduction: Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice with a higher occurrence in the elderly and rarely occurs in pediatric patients with a structurally normal heart. Bayes syndrome has been described as the occurrence of AF in the elderly associated with electrocardiogram (ECG) findings of interatrial block by the Bachmann bundle, and there are no reports of cases in pediatrics so far. The reduced atrial myocardium mass in children makes the occurrence of AF difficult, reinforcing the mechanism triggered by the interatrial delay. Case Report: S.R.C., male, 5 months old, in December 2018, admitted to a public hospital in Teresina-PI due to respiratory distress reported by the mother, which had been frequent since birth. Born at term, with no pathological antecedents. On physical examination, he had a 2+/4+ systolic murmur in the mitral area, irregular heart rhythm, high heart rate (HR), normal vesicular murmur, without adventitious sounds or signs of pulmonary edema. On admission, an echocardiogram (ECHO) was performed, which showed dilated left chambers, left ventricular ejection fraction of 55% and mild mitral and tricuspid regurgitation. The admission ECG showed AF with HR around 180 bpm and episodes characteristic of Ashman's phenomenon. After reversal, in sinus rhythm, morphological alterations of the p wave characteristic of interatrial delay by Bachmann's bundle were evidenced, a fixed alteration associated with a greater predisposition to the occurrence of AF. The patient used antiarrhythmic medications, with complete normalization of the ECHO and maintaining long-term sinus rhythm on an outpatient basis. Final Considerations: We report a rare case of Bayes syndrome in an infant with AF and mild tachycardiomyopathy associated with an electrocardiographic alteration characteristic of a fixed conduction disturbance in the Bachmann fascicle due to interatrial delay. The presence of Bachmann's bundle block on the electrocardiogram justifies the pathophysiological mechanism of the arrhythmia as a probable etiology, as it is a known risk factor for AF and no other clinical alteration was evidenced that would justify the occurrence of arrhythmia in this patient. 111450 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Characteristics and Progress of a Twin Pregnancy with an Acardiac Fetus PEDRO HENRIQUE TORRES TIETZ1, Vitor Agne Magnus1, Marco Antonio Vinciprova Dall'Agnese1, Gabriel de Paula Alves1, Jorge Alberto Bianchi Telles2 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA); (2) Hospital Materno Infantil Presidente Vargas (HMIPV) Introduction: A twin pregnancy with an acardiac fetus is a rare event, with a low number of cases in the literature describing conservative treatments and parameters to be assessed. Case Description: 29 years old female with a 14 week pregnancy presented to fetal medicine service due to an ultrasound evidencing a monochorionic and diamniotic twin pregnancy. One of the fetuses had a malformation in the superior part of the body, suggestive of an acardiac fetus. The patient was submitted to fetal ultrasound which confirmed this diagnosis of twin reversed arterial perfusion (TRAP). The patient was assessed for possible laser ablation of the umbilical cord. There weren't any signs of hemodynamic decompensation on the pump twin and a blood flow almost restricted to the umbilical cord on the acardiac fetus, without surgical indication at that moment. The 22 week ultrasound showed no morphologic alterations on the pump twin, which weighed 560 g, and a dysmorphic mass of 160 g representing the acardiac fetus. There was evidence of vascularization in its interior shown by a doppler ultrasound. The doppler echocardiogram and a magnetic resonance imaging were also normal for the pump fetus. The acardiac fetus still presented to be a misshapen mass with significantly peripheral edema. Ultrasounds were regularly made as of the 26 weeks of gestation, aiming at the early diagnosis of any sign of cardiac decompensation of the pump fetus. The evaluated parameters consisted on the relation between the weight of the acardiac and pump fetuses, cardiothoracic ratio, visualization of tricuspid regurgitation, presence of polyhydramnios and doppler ultrasound of the venous duct in the pump fetus. These parameters stayed normal and it was decided to hospitalize the patient with 30 weeks of gestation for an ultrasound follow-up and for daily cardiotocography (CTG). The CTGs were normal. The pump fetus, a girl, was born with 33 weeks of pregnancy and weighing 2.125 g, presenting an Apgar score of 8/9. The acardiac fetus weighed 1.090 g, being a misshapen mass, with more developed inferior limbs. The pump twin presented a respiratory failure. However, she progressed without major complications, being discharged 14 days after birth. Conclusion: Although there is not a well defined pattern established for the management of twin pregnancy with an acardiac fetus, some factors like early diagnosis and hemodynamic assessment can help future cases to end successfully. 111476 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Brugada Phenocopies in a Pediatric Patient with Ventricular Pre-Excitation: A Case Report GABRIEL SILVA DE CARVALHO PONCIANO1, Amanda Metsa da Silva Cardoso1, Henrique Lobo Saraiva Barros2, Rafaela Marrocos Bezerra2, Sonia Maria Cavalcante da Rocha2 (1) Universidade do Estado do Rio Grande do Norte - UERN; (2) Policlinica dr. Luiz Carlos Fontenele - SPDM Introduction: Brugada Syndrome (BrS) is a genetic disease of low worldwide prevalence and male preponderance, which can lead to severe arrhythmias. The diagnosis includes an electrocardiogram (EKG) with the presence of spontaneous or drug-induced ST elevation, followed by a symmetrical negative T wave in the right precordial leads and clinical features. Brugada phenocopies present an EKG pattern equivalent to BrS, but may arise from a previus ventricular repolarization alteration or associated with factors like hydroelectrolytic disorders. Such changes might generate a transmural myocardial gradient or delay the conduction around the right ventricular outflow tract, inducing the EKG pattern. This diagnosis includes EKG pattern, low pretest probability for the syndrome, drug and genetic testing. Case Description: A 6 years old male child with psychomotor agitation was sent to cardiological evaluation in order to use methylfnidate. There were no heart complaints and a negative family history of sudden death or arrhythmic syncope. Short PR interval and delta wave were seen in all EKG leads. A 24H Holter monitoring was requested, which showed a short PR and delta wave throughout the tracing and no documented arrhythmias. Ventricular pre-excitation became the main diagnostic hypothesis. It was indicated a careful follow-up for the child. In early 2022, during a routine appointment, the child showed no heart complaints, but he was in a recovery from gastroenteritis. The EKG showed a pattern of type 1 BrS. The EKG was repeated after 2 days with no more BrS pattern. The possibility of BrS was ruled out due to the absence of clinical features, normalization of the EKG and negative family for BrS. For that ocasion the diagnosis of phenocopies seemed more likely to be suitable. Conclusion: Considering phenocopies as a differential diagnosis of Brugada syndrome is important. A complete investigation of the patient is necessary for the diagnostic suspicion, considering the possible related factors for the condition. A careful follow-up along with a complete explanation of this entity is the best way of deal with this case. 111594 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Midventricular Form of Takotsubo Cardiomyopathy: A Clinical Entity that Needs to be Recognized STHEPHANY YAMAGUCHI DE MELO1, Sthephany Yamaguchi de Melo1, Isabela Souza Cruvinel Borges1, Danielle Campos de Almeida1, Joao Lucas O'Connell1 (1) Universidade Federal de Uberlandia - UFU Introduction: Takotsubo cardiomyopathy (or broken heart syndrome) is characterized by transient left ventricular systolic and diastolic deficits, mimicking acute coronary syndrome (ACS). It is more common in women (9:1), elderly, with a history of psychiatric disorder and physical or emotional stress. Classically, the ventricular abnormality is analogous to the Japanese pot used to fish for octopus, which resembles the apical ballooning of the typical form of the disease. The description of this case highlights the possibility of other regional abnormalities (less common) that have also been described in the literature: the one that evolves with midventricular akinesia, with severe hypokinesia restricted to the middle ventricle. Case Description: Female patient, 54 years old, hypertensive, smoker and anxious. She presented with syncope at home after emotional stress and being taken to the emergency room. Electrocardiogram: discrete infra-ST on the anterior wall. Elevation of myocardial necrosis markers. Coronary angiography: absence of obstructive coronary lesions; Significant hypokinesia of the middle segments with moderate global systolic dysfunction suggestive of Takotsubo cardiomyopathy of the midventricular form. He evolved well and was discharged with optimized clinical treatment for ventricular dysfunction. She is asymptomatic and with full recovery of contractility and ventricular function one year after the initial condition. Conclusion: Although most cases are benign, Takotsubo heart disease is a potentially fatal disease, with a severe and irreversible course. Diagnostic criteria aim to identify acute left ventricular dysfunction and treatment is directed towards heart failure that sets in. Despite not being a diagnostic criterion, cardiac catheterization is commonly performed to rule out ACS. When performed, the absence of coronary artery disease is expected. Echocardiography and myocardial resonance assist in the diagnosis and identification of ventricular abnormalities that are sudden and without a defined time for reversibility. The mid-ventricular form represents a minority of cases (15%). Its benign character has been questioned in recent reviews due to the number of underestimated cases that may evolve unfavorably without a well-established prognosis. 111597 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY "Valve-in-David", a New Face of Structural Interventional Cardiology GUSTAVO LUIZ MONTENEGRO DA COSTA1, Dany David Kruczan2, Lilian Soares da Costa2, Edgard Freitas Quintella2, Marcio Jose Montenegro da Costa2 (1) Faculdade Tecnico-Educacional Souza Marques; (2) Instituto Estadual de Cardiologia Aloysio de Castro Introduction: Valvular heart disease is an important contributor to morbimortality worldwide. This case report proposes to switch a redo operation on a valvular aortic regurgitation, in a 60-year-old man post David procedure for a transcatheter aortic valve replacement (TAVR-in-David). Case Description: A 60-year-old man, after almost a 10-year outpatient follow-up due to a prior David procedure, presents onset of dyspnea with minimal exertion and chest pain in July 2021. Until March 2022, this patient was managed even optimal medical treatment has kept non-responsiveness and then was admitted in our hospital. The first choice of treatment during this admission was the conventional surgery for aortic valve replacement, but the surgical team denied the procedure due to the high risk of complications. Then we have implanted a balloon expandable valve with no leak and good final result. TAVR should be contemplate in the role of procedures as a final solution for severe aortic regurgitation in case of high surgical risk or inoperable patients, especially in centers of excellence. Conclusion: The decision to treat a patient with a TAVR-in-David procedure is off label but we believe that with permission of the patient and, a multidisciplinary approach to get the best decision must be a rule inside Cardiology. In conclusion, we need a series of cases and a follow-up to validate this new proposal to switch a redo David procedure for a V-i-David transcatheter. 111600 Modality: E-Poster Scientific Initiation - Case Report Category: ACUTE AND CHRONIC CORONARY DISEASE/THROMBOLYSIS Spontaneous Coronary Artery Dissection by a Woman in Early Postpartum RODRIGO LACERDA GERVOU1, Daniel Luiz Messias Pereira1, Miguel Angelo Ribeiro2, Natalia Dominguez Paes Leme2, Nathalia Duarte Camisao2 (1) Universidade Federal do Estado do Rio de Janeiro UNIRIO; (2) Hospital Norte D'or Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), myocardial infarction and sudden death, but becomes more relevant in younger women, with multiple pregnancies, especially in the puerperium phase, which consists of 2-18% of all cases of SCAD. It has few association with atherosclerotical risk factors but emotional stress preceded in 50% of the cases, SCAD consists in a non-traumatic, non-iatrogenic separation of the coronary arterial wall resulting in an ischemic event and myocardium injury, that may represent up to 1-4% of total ACS events. Case Report: A 39 years-old female patient arrives in the Emergency Room, reporting typical chest pain, started after the news that her newborn child had been transferred to the neonatal UCI, she referred of a similar pain one week ago, but with spontaneous cure. She has a history of arterial systemic hypertension but no other risk factors for atherosclerotic disease. An Electrocardiogram showed repolarization alteration in the Inferior wall and a small elevation of the ST segment in V2-V4. Echocardiogram stated a moderate dysfunction of Left Ventricular function (LVEF) and akinesis of apical segments. The patient was forwarded to coronary angiography that revealed SCAD of the left anterior descending artery, after diagonals branch. Due to the etiology of the coronary disease, opted for optical medical treatment, and no angioplasty was performed. Magnetic resonance Imaging showed poor LVEF of 40%, 11% infarcted area with disproportion between the ventricular dysfunction and the size of the ischemic area, suggesting a large stunned area that could become functional again. As the literature states, because of the risks of coronary angioplasty, especially without arterial oclusion, patient was discharged from hospital with optical medical treatment for heart failure. Conclusions: SCAD is not a common cause of ACS, but is associated with great mortality and morbidity. It is an important etiology and deserves our attention so we can have it in mind, identify and to have the best approach to this pathology. 111608 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Treatment of Superior Vena Cava Syndrome Caused by Tuberculous Lymphadenitis with Spiral Saphenous Vein Graft: A Case Report FABIO ANTONIO SERRA DE LIMA JUNIOR1, Andre Loureiro Fernandes1, Isaac Newton Guimaraes de Andrade1, Petrucio Abrantes Sarmento1, Andre Telis de Vilela Araujo1 (1) Universidade Federal da Paraiba Introduction: Tuberculous lymphadenitis is a rare cause of superior vena cava syndrome (SVCS). All of literature cases report a conservative or an endovascular approach to treat these cases. Case Description: We aim to report a 42 years old female case who was allergic to two components of both standard and alternative tuberculosis treatment, and required a surgical approach. However, the same patient had a large and excessively calcified tuberculous node exponentially decreasing the preview success rate of a possible endovascular approach, due to the risk of drift. On the case, the surgical team chose to execute a spiral saphenous vein graft, a method previously reported to treat SVCS, but never on association to tuberculous lymphadenitis. Conclusion: When treating superior vena cava syndrome, etiologies that induce intense vein fibrosis, such as mediastinal tuberculosis, may be unsuitable for endovascular treatment. In these cases, open surgical bypass using a spiral venous graft is an achievable and effective option for symptoms relief, with satisfactory long-term patency. 111758 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Chronic Total Occlusion Percutaneous Coronary Intervention for Correction of Ischemic Mitral Regurgitation: A Case Report MONIQUE DE SOUSA LOPES1, Debora dos Santos Silva1, Bruno Goncalves Machado1, Aline Viana Alves1, Ewerton de Souza Abreu2 (1) Centro Universitario Faminas Muriae (FAMINAS); (2) Hospital Prontocor de Muriae (PRONTOCOR) The main indication for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is to improve anginal symptoms, being considerable when there is resistant angina or ischemia compatible with the territory of the occluded artery, however, there is no routine evidence of this approach for correction of ischemic mitral regurgitation (IMR). This study analyzed a 51-year-old patient, without previous comorbidities, with stage B Congestive Heart Failure. Transesophageal Echocardiogram showed severe Mitral Insufficiency, regurgitant jet and incomplete coaptation due to wide prolapse of the posterior leaflet, raising the hypothesis of IMR due to dysfunction of the posteromedial papillary muscle. Invasive coronary stratification revealed CTO in the middle third of the right coronary artery (RCA). Due to the persistence of symptoms despite optimized clinical treatment, a percutaneous approach to the RCA CTO was decided. With failure of an antegrade angioplasty, a retrograde approach was performed using the dissection and reentry technique, which was successful with positive results, including improvement of heart failure symptoms and immediate papillary dysfunction, confirming the diagnostic hypothesis. At ten-month follow-up after the procedure, the patient remains asymptomatic, with fully preserved physical and functional capacities and mild mitral regurgitation. Therefore, despite the technical limitations associated with the procedure and the need for further quality studies to better define the indications, specifically regarding the IMR, it is suggested that the approach for such purpose, when well indicated, may be a promising possibility within the interventional cardiology, impacting on the increase of survival and expanding the prospects of treatment. 111779 Modality: E-Poster Scientific Initiation - Case Report Category: HEMODYNAMICS AND INTERVENTIONAL CARDIOLOGY Effect of Lipid Therapy in a Patient with Cardiogenic Shock Due to Alpha and Beta-Blockers Intoxication: A Case Report YURY PIFANO VARELA1, Marina Coelho Feitosa1, Caio Pessoa Cruz2, Isabelly Crysthynne Moreira da Luz3, Polianna Lemos Moura Moreira Albuquerque4 (1) Academico do Curso de Medicina da Universidade de Fortaleza - UNIFOR; (2) Academico do Curso de Medicina da Universidade Estadual do Ceara; (3) Academico do Curso de Farmacia da Universidade Federal do Ceara; (4) Medica Nefrologista do Instituto Dr. Jose Frota e Coordenadora do Centro de Informacao e Assistencia Toxicologica (CIATox/IJF). Doutora em Ciencias Medicas pela Universidade Federal do Ceara - UFC Introduction: Intoxication by selective a-1 and b-1 adrenorreceptor blockers may cause serious repercussions in the cardiovascular system, that can progress to Cardiogenic Shock, which can lead to death in 80% to 90% of patients. There are successful reports using 20% lipid emulsion (20% ILE) as treatment after cardiovascular collapse caused by lipophilic agents such as tricyclic antidepressants, propranolol, verapamil, bupropion and barbiturates, although the literature still does not assign a standard protocol. This report case demonstrates the emergency use of 20% ILE in acute toxicity from attempted suicide through ingestion of doxazosin and metoprolol. Case Description: A.H.M.L, 61 years old, male, admitted by a tertiary care hospital, reference in toxicological assistance, in Fortaleza/CE, in critical condition, 8 hours after intentional and unquantified ingestion of metoprolol and doxazosin. At admission, patient on mechanical ventilation, without sedoanalgesia, Glasgow Coma Scale 3, using high doses of vasoactive drugs (noradrenaline 40 ml/h + vasopressin 4 ml/h) (Table 1). With no response to the standard protocols for hemodynamic shock, it was suggested a therapeutic regimen with 20% ILE in 3 doses of 1 ml/kg (60 ml), implemented at intervals of 10 min, resulting in immediate hemodynamic upturn - distressed awakening and improvement in ventilatory parameters (Table 1). After 5 hours, it was necessary to repeat the 20% ILE regimen due to clinical instability. Over the 28 days of hospital stay, the initial high doses of vasoactive drugs were reduced without clinical complications. In addition, renal replacement therapy was performed (two sessions). Conclusion: This is the first successful experience in the state of Ceara for the treatment of Cardiogenic Shock resulting from intoxication by selective a-1 and b-1 adrenorreceptor blockers agents. The study provides evidence on the use of 20% ILE as a relevant therapy in patients after cardiogenic shock due to high ingestion of alpha and beta blockers. 111794 Modality: E-Poster Scientific Initiation - Case Report Category: PERICARDIUM/ENDOCARDIUM/VALVOPATHIES Viral Pericarditis Associated with Denge Infection: A Case Report RAIMUNDO BENICIO DE VASCONCELOS NETO1, Ana Caroline Leite Guedes1, Rebecca Shaiane Soares Nunes Rivoredo1, Fernanda Gabry Scazuza Gomes de Souza1 (1) Centro Universitario Sao Lucas-UNISL Introducao: Dengue is a viral infectious process transmitted by Aedes aegypti and most of it presents with a limited high condition, however, the endemic outbreaks of the disease open the way for the emergence of serious cases with complications. Cardiac involvement associated with dengue is a rare and broad-spectrum process, in which pericarditis and pericardial effusion have a lower occurrence. The pathophysiology of such involvement is still uncertain, but it is believed that viral infection in the pericardium can generate the release of inflammatory cytokines that cause dysfunction in the cardiac endothelium, and that promote increased vascular permeability, culminating in fluid leakage to the third space. and generating the process of pericardial effusion, which in most cases does not constitute an accentuated process. This article aims to report a case of a patient with pericarditis and mild pericardial effusion as a complication of dengue. Relato: Female patient, 81 years old, hypertensive, with advanced stage of Alzheimer's disease, was taken to the emergency room by family members who reported a decline in general condition, unmeasured fever and lowered level of consciousness. On admission, the patient presented Glasgow Coma Scale 14, was febrile, and diffuse rashes associated with significant swelling in the upper and lower limbs were observed. She was mildly dyspneic and hypoxemic, requiring the use of complementary oxygen therapy. In view of the symptoms presented, complementary exams and transthoracic echocardiography (TTE) were requested due to the suspicion of cardiac insufficiency. The hemogram results showed significant thrombocytopenia and leukometry within the normal range, serology was requested for dengue, which showed positive IgG and IgM for the viral infection. The TTE showed hyperrefringence of the pericardium and small effusion, concluding the diagnosis of viral pericarditis. The patient remained in the intensive care department under infectious, neurological and hemodynamic surveillance, with subsequent clinical improvement. Conclusao: The present report points to the unusual association between pericarditis and dengue, which demonstrates the importance of a thorough clinical management and an accurate look at the individual, since the signs can vary from mild to severe, including pericardial effusion. If treated satisfactorily, they potentially increase the chances of restoring the patient to health. 111800 Modality: E-Poster Scientific Initiation - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Acute Myocardial Infarction Secondary to Coronary Thrombosis in a Patient After Mild COVID-19: Case Report MARIANA FURTADO DE SA1, Vanessa Ortega1, Vinicius Eiji Kameoka2, Bianca Altrao Ratti Paglia1 (1) Universidade Cesumar - Unicesumar; (2) Hospital Parana Introduction: SARS-COV2 has been shown to be a virus that affects multiple organs, including the heart. This case report shows a severe cardiologic complication in a patient post mild COVID-19. Case Report: L.M.B, 37 years old, female, former smoker (10 pack-years) and with no medical conditions, reports mild COVID-19 two months before an episode of intense retrosternal burning associated with diaphoresis. Initial electrocardiogram (ECG) without ischemic alterations, however, due to the recurrence of the pain, she returned to the emergency room after two days, in which diffuse ST elevation was evidenced in new ECG, associated with pleuritic chest pain. The patient was referred for coronary angiography (CA) and later cardiac magnetic resonance imaging (CMR). CA: Absence of atherosclerotic process. Distal occlusion of the left anterior descending. Residual thrombus in marginal branch. CMR: Apical transmural infarct. Intracavitary thrombus in apex. Acute Pericarditis. Conclusion: Inflammation and hypercoagulability generated by COVID-19, increase the chances of cardiovascular events, such as the myocardial infarction evidenced in the case, even in the absence of significant risk factors. Therefore, the importance of studies is emphasized, to identify groups that will benefit from prophylactic therapies, avoiding similar outcomes. 111825 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Atrial Mixoma with Cardioembolic Manifestations - When Should we Anticoagulate: A Case Report JOYCE FERNANDES COSTA1, Thaissa Santos Monteiro2, Fabio Akio Nishijuka2, Maria Carolina Terra Cola2 (1) Universidade Estacio de Sa - UNESA; (2) Instituto Nacional de Cardiologia - INC Introduction: Cardiac tumors are rare, the majority being benign and atrial myxoma (AM) is the most common type. Most are symptomatic and may present Goodwin's triad, with intracardiac obstruction, embolic manifestations and constitutional symptoms. The diagnostic method is echocardiography (ECO), assessing size and location of the tumor. Surgical resection is recommended. Anticoagulants may be indicated if embolic signs are present, although evidence points not to be an alternative to surgery, as half develop cerebral ischemia despite the anticoagulation. Local recurrence is uncommon and annual ECO follow-up is recommended for 4 years after tumor resection. Case Report: Female, 35 year-old, hypertensive, smoker, obese grade I and family history of coronary artery disease. Admitted with severe chest pain, blood pressure of 220 x 100 mmHg, right bundle branch conduction disorder and positive myocardial necrosis markers, diagnosed with acute myocardial infarction type II. Recent history of transient focal deficit in the left upper limb. Presented cutaneous lesions resembling Janeway lesions in hands and feet, but tender. ECO observed an heterogeneous and irregular mass in the left atrium adhered to the atrial septum, measuring 5.2 x 3.6 cm, projecting to the mitral valve orifice, without significant obstruction, suggestive of AM. The patient was then transferred to our institution, and the screening for COVID-19 was positive, but with normal chest tomography (CT) and no related symptoms. Coronary angiotomography performed later showed no coronary obstructions, and head CT showed no signs of ischemia. Full anticoagulation was started due to the possible cardioembolic nature although there were no CT evidence for ischemia, while waiting for surgery. She underwent resection of the mass with atrial septoplasty. Postoperative ECO showed no shunt through the atrial septal and absence of intracavitary mass. There were no surgical complications on follow-up. Conclusion: AM manifests itself in different ways and with imminent risks. Immediate surgical intervention is important, due to the risk of embolism, and in cases of previous embolic events, anticoagulation may also be considered, due to the risk of associated thrombi with the tumor. 111867 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Type B Interrupted Aortic Arch with Ventricular Septal Defect in an Adult with Eisenmenger Syndrome and Features of Vacterl Association HALAN VITOR CORREIA EVANGELISTA VIEIRA1, Catarina Vasconcelos Cavalcanti1, Paulo Ernando Ferraz Cavalcanti1, Ricardo Felipe de Albuquerque Lins1, Monica Cristina Rezende Fiore1 (1) Pronto Socorro Cardiologico de Pernambuco (PROCAPE); (2) Universidade de Pernambuco (UPE); (3) Faculdade de Ciencias Medicas da Universidade de Pernambuco (FCM-UPE) Introduction: Correlation between clinical findings and study with transthoracic echocardiography and angiotomography allow diagnosis of rare congenital heart disease in adult patient. Case Description: A 42-year-old female patient with a long-standing history of cyanosis and abdominal discomfort, presenting worsening of symptoms in the last months was admitted at our center. The physical examination revealed cyanosis and digital clubbing with outstanding difference between upper and lower limbs, since the right hand was quite normal. Placing oximeter probe on her fingers and toes when breathing room air, differential peripheral oxygen saturation (SpO2) preserving the right hand was noted (Right fingers 99%, left fingers 94% and toes 88%). A loud second cardiac sound with fixed splitting was heard, as well as a systolic murmur in the left sternal border. Two-dimensional transthoracic echocardiography revealed a ventricular septal defect (12.1 mm) and the color Doppler showed bidirectional flow across the ventricular septal defect (VSD). The estimated systolic pulmonary artery pressure was 105 mmHg. An angiotomography was performed due to difficulties in the analysis of the aortic arch, revealing a type B aortic arch interruption associated with VSD and a patent ductus arteriosus as well as signs of severe pulmonary artery hypertension. Severe kyphoscoliosis for her age as well as incidental finding of ectopic kidney in the pelvis were also revealed. Deoxygenated blood from right ventricle flows into the descending aorta and left subclavian artery through the patent ductus arteriosus preserving the right hand from the long-term effects of deoxygenated blood. A hypothesis of VACTERL association was also formulated in view of the demonstrated features: V, vertebral anomaly by kyphoscoliosis; C, cardiac anomaly due to type B aortic arch interruption with interventricular communication; and R, renal anomaly with the left kidney in pelvic location. Conclusion: The clinical and anatomical findings described and the rarity of the pathology in this adult patient (Not surgically treated) make this case report unique. 111876 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR SURGERY Coronary Arteriovenous Fistula as a Cause of Angina: A Case Report REBECCA SHAIANE SOARES NUNES RIVOREDO 1, Raimundo Benicio de Vasconcelos Neto1, Ana Caroline Leite Guedes1, Fernanda Gabry Scazuza Gomes de Souza1 (1) Centro Universitario Sao Lucas/Afya UNISL Coronary fistulas are rare congenital anomalies that constitute connections between the coronary artery and the heart chambers (coronary-cameral fistula) or with the venous system of the myocardium (coronary arteriovenous fistula). This fact is due to the malformation of the individual's cardiac vascular system, which presents continuity of the embryonic sinusoids of the myocardium, which are responsible for the formation of the perforating arteries and the right and left coronary trunks, and should close during the gestational period. Coronary arteriovenous fistulas are one of the rarest cases of this pathology, usually causing symptoms only after the 4th decade of life, which course with heart failure, angina, arrhythmias or endocarditis. The intervention of the pathological condition is established according to the patient's condition, consisting of factors such as cardiovascular symptoms, fistula drainage volume and myocardial ischemia. This is a case report of a patient with an arteriovenous fistula in the right and circumflex coronary artery leading to the coronary sinus. Report: Female patient, 47 years old, hypertensive, diabetic and dyslipidemic. She sought medical care due to exertion angina, which started 3 months ago, of a progressive nature, having intensified in the week preceding hospitalization, which motivated her to seek care. She was received with type A chest pain, at rest, with an electrocardiogram showing anteroseptal subendocardial ischemia. At no time did she present positive myocardial necrosis markers, and she was treated as high-risk unstable angina and underwent coronary angiography that showed coronary arteriovenous fistulas (CAF) in the paths from the right coronary artery to the coronary vein and from the circumflex artery to the coronary vein. After diagnosis, in-hospital clinical treatment was optimized and the patient was referred to the cardiovascular surgery service for fistulization correction. Conclusion: The aforementioned case brings to light a discussion about coronary arteriovenous fistula associated with anginal cause, which, although rare, when detected early and managed clinically and surgically in an adequate and satisfactory manner, evidences the relief of symptoms and improvement in the patient's quality of life. 111929 Modality: E-Poster Scientific Initiation - Case Report Category: NEGLECTED CARDIOVASCULAR DISEASES Takayasu's Arteritis - When to Intervene? PEDRO LUCAS CARDOZO BARROS1, Ana Flavia Silveira de Souza1, Joana Raquel Cardoso dos Santos1, Hellen Dutra Passos2, Jose Augusto Soares Barreto Filho1 (1) Hospital Universitario da Universidade Federal de Sergipe (HU-UFS); (2) Hospital Sao Lucas, Rede D'or Sao Luiz (HSL) Takayasu's arteritis (TA) is a chronic inflammatory disease of unknown etiology. It is a rare vasculitis involving the aorta and its main branches in which transmural granulomatous inflammation causes multiple arterial lesions. The present report is about a 32-year-old female which physical exam exposed asymmetric radial pulses and significant pressure difference between upper limbs. She was subjected to a tomography of thoracic and abdominal aorta for the investigation of an abdominal murmur and possible secondary arterial hypertension. Angiography then revealed diffuse arterial injuries, including dissection of right renal artery, stenosis of left renal artery and at infrarenal portion of abdominal aorta and fusiform aneurysm upstream. Outpatient follow-up almost 6 years after the diagnosis of TA reveals a completely asymptomatic individual without prior hospitalization or any other intervention besides conservative treatment. The woman has a history of two pregnancies among one abortion, practices regular physical activity and maintains all work performance. Her blood pressure is controlled; thoracic radiography, electrocardiogram and laboratory exams are all normal; and both transthoracic echocardiogram and Holter show discrete and unspecific cardiac alterations. Studies have demonstrated that few patients with symptomatic TA require surgery. The procedures indicated for occlusive disease are endovascular stent and arterial bypass; the aneurysmal form of TA may require arterial reconstruction by open surgery or endovascular approach. However, current literature lacks significant evidence to indicate most invasive treatments for asymptomatic individuals. Our patient's clinical presentation is stable, thus not requiring invasive procedures despite of diffuse arterial injuries. 111939 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Hyperthrophic Cardiomyopaty and Marfan Syndrome: Case Report of Complex Cardiopathy Association GABRIELLA GOMES FERNANDES MAIA1, Rafael Souza Conceicao da Silva2, Claudia Regina de Oliveira Cantanheda1, Dany David Kruczan1, Marcio Montenegro1 (1) Instituto Estadual de Cardiologia Aloysio de Castro - IECAC; (2) Unigranrio Barra da Tijuca Marfan syndrome is an autosomal dominant multisystem connective tissue disorder caused by mutations in fibrillin. HCM is a inherited disease caused by mutations in genes encoding sarcomeric proteins in the heart cells. The estimated incidence rate for Marfan syndrome is 1:5000, while for HCM is 1:500. Both association has no incidence, which explains the motivation of this case report. A 39-year-old female patient, reporting dyspnea on exertion for 2 years and palpitations for 18 months, presents with HTN and a murmur, which progressed to dyspnea on moderate exertion, diaphoresis and lipothymia. After 6 months, she presented a dry cough and chest discomfort such as tingling, radiating to the left arm and jaw. She uses antihypertensive drugs. History of descending aortic endoprosthesis in 2016. On physical examination, normal HR and BP. Abnormal kyphoscoliosis. Ogival palate and Steinberg's sign. Regular and wide pulses. Palpable Ictus without deviation. On auscultation, mitral focus with hypophonetic sounds, holosystolic murmur and S3. In the supine position, the systolic murmur increases with expiration. In left lateral decubitus, it increases after inspiration. Mesocardium with hypophonetic sounds, systolic murmur and gallop. Accessory aortic focus with systolic murmur radiating to clavicles, carotids, and suprasternal notch, and an diastolic murmur. Pulmonary focus with a rough protosystolic murmur, well audible diastolic murmur and split S2. The X-ray shows slight cardiac enlargement and aortic calcification. ECG shows sinus rhythm, cardiac axis at -30deg and alteration in ventricular repolarization. ECHO shows increased of LA and RA, asymmetric LV hypertrophy with reduced contractility but preserved global systolic function; MR with intense anterior systolic motion, AR with failure of central coaptation; big dilation of the ascending aorta plus descending aortic dissection. Diagnosed with Marfan syndrome, severe AR and MR, dilated ascending aorta and HCM. Surgical correction with Myectomy, placement of Aortic Valve Tube and mitral valve replacement was indicated. However, due to technical problems, the responsible institution chose to perform only the aortic valve replacement with a biological prosthesis. Currently, the patient remains symptomatic and Percutaneous Septal Alcoholization is indicated, due to a safer and more effective conclusion for the case. It was preferred a less invasive technique, since the main outcome is to provide quality life. 111982 Modality: E-Poster Scientific Initiation - Case Report Category: COVID-19 AND CARDIOVASCULAR SYSTEM Acute Pericarditis in Scholar 3 Weeks After Infection by COVID-19: A Case Report GABRIELA ZIMMERMANN1, Melissa Dorneles de Carvalho1, Thamara Andressa Fagundes1, Fernando Caritas de Souza1, Giolana Mascarenhas da Cunha1 (1) Universidade Estadual do Oeste do Parana (UNIOESTE) Pediatric presentation of coronavirus disease 2019 (Covid-19) rarely includes severe complications in acute phase; however, characteristics of the condition among children are not yet fully established. We report a case of a scholar who presented developed acute pericarditis, tested positive for Covid-19, progressed to myopericarditis and had completely recovery after the therapeutic management. Male, 11 years old, previously healthy, referred chest pain, for over one hour, no radiating, that started suddenly in prone position and presented spontaneous remission. Fourteen hours later he felt the same symptoms, so he was taken to the emergency service. An electrocardiogram (EKG) showed alterations that could suggest infarction, nonetheless, considering the patient's symptoms and age, the heart attack was rejected, and pericarditis was the most likely hypothesis. The patient denied having fever or dyspnea, but a flu episode about twenty-five days earlier. Physical exam had no irregular findings. Laboratory evaluation included leukocytes 12.820/mm3, erythrocyte sedimentation rate 20 mm/h, troponin I 19.572 ng/mL, pro B-type natriuretic peptide 790 pg/mL, C-reactive protein 5,9 mg/L, lactate dehydrogenase 335 mg/dL, D-dimer 222 ng/mL and COVID-19 serology results: IgG positive and IgM negative. With the orientation to make EKG's series, another exam was performed , which presented ST-segment elevation in D2, D3, avF and precordial leads. Echocardiogram was conclusive with pericarditis. The treatment included nonsteroidal anti-inflammatory drugs (ibuprofen and high-dose aspirin) for two weeks. The hospital length of stay was 4 days, the scholar turned asymptomatic, and EKG was normal. The patient was not vaccinated against SARS-Cov-2. This is a case of pericarditis after SARS-Cov-2 infection that might be a useful reference to other clinicians caring for pediatric patients affected by COVID-19 and contribute to the differential diagnosis of chest pain. Despite the rapidly growing research on management of COVID-19 and its complications, there are many unanswered questions and areas to explore. 111984 Modality: E-Poster Scientific Initiation - Case Report Category: CARDIOVASCULAR IMAGING Non-Invasive Diagnosis of Cardiac Amyloidosis by Technetium-Pyrophosphate Scintigraphy: A Case Report ALICE ZANETTI DUSSIN1, Alice Einsfeld Britz1, Juliana Menezes Zacher1, Barbara Dewes Silva1, Joao Carlos Vieira da Costa Guaragna1 (1) Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) Background: Transthyretin amyloidosis (ATTR) is the main cause of cardiac amyloidosis and it is presented by clinical manifestations such as heart failure, diastolic dysfunction, left ventricular hypertrophy, atrial fibrillation (AF) and aortic stenosis. Technetium-pyrophosphate (Tc-99m-PYP) scintigraphy has a fundamental diagnostic role in differentiating types of amyloidosis, being able to detect the presence of transthyretin deposits. Case Report: A 85-year-old diabetic female, with a history of multiple hospitalizations due to decompensated heart failure and chronic obstructive pulmonary disease since 2009. Patient brought a 2009 transthoracic echocardiogram (TTE) - ejection fraction (EF) of 74%, all cavities had normal dimensions - and two myocardial scintigraphy from the same period with low probability of ischemia. Five years ago, was presented with acute chest pain and underwent coronary angiography that showed coronary arteries without obstructions. Soon after, she started having syncopal episodes. Three years ago, started experiencing dyspnea on moderate efforts, and was diagnosed with AF; cardioversion was successfully performed. Thirty days later, she once again presented AF with worsening dyspnea, lower limb edema, jugular swelling and hepatomegaly. At the time, a chest tomography (cardiomegaly, right pleural effusion and enlargement of the pulmonary trunk) and a TTE (EF of 68%, left ventricle with normal diameters and biatrial overload) were executed. A cardiac magnetic resonance also showed biatrial enlargement. A Tc-99m-PYP scintigraphy was then requested, which diagnosed grade 2-3 ATTR. Conclusion: Cardiac amyloidosis is a rare, progressive and lethal pathology; and its incidence has increased due to advances in cardiovascular imaging. A Tc-99m-PYP scintigraphy, for example, has a sensitivity of 90% and specificity of 97% for the diagnosis of ATTR. Therefore, it is extremely important for the cardiologist to be acquainted with this method, since this can allow an early diagnosis of ATTR without the need for invasive tests, such as biopsy, which is still considered the gold standard for diagnosis. 112065 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Prenatal Findings of a Case of Imperfect Twinning JULIANA ROSSI CATAO1, Guilherme Girardi May1, Eric Schwellberger Barbosa1, Henrique Perez Filik1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) Introduction: Imperfect twinning occurs in 1 in 100 monozygotic twins. Our aim was to report the prenatal findings of a case of conjoined thoracopagus twins. Case Presentation: The patient was a 31-year-old pregnant woman in her fourth pregnancy. She was referred to the fetal medicine service due to an ultrasound at 12 weeks gestation, with a description of twins united in the abdomen. The examination at 14 weeks revealed that the twins were united at the chest and upper abdomen. There was apparent sharing of heart and liver. A single umbilical cord emerged caudally to the union of the fetuses. The emergence of the umbilical arteries was observed laterally to the bladders. The pregnancy was monochorionic and monoamniotic. Echocardiography revealed a normal fetus on the left and a fetus on the right with dextrocardia. Second trimester ultrasound, performed at 22 weeks of pregnancy, showed no morphological changes in the fetuses. Two venous ducts were visualized. The echocardiography performed soon after revealed an apparent communication of the hearts through the right atrium of the fetus located on the right with the left atrium of the fetus located on the left. The fetus on the left had a tetralogy of Fallot with pulmonary atresia. There was a large infundibular perimembranous ventricular septal defect with a large caliber aorta riding the trabecular septum in 50% of its annulus. Magnetic resonance imaging revealed fetuses fused through the thorax and upper abdomen, above the umbilical cord insertion. The right lobe of the liver of fetus one was related to the left lobe of the liver of fetus two. There were two stomachs and two gallbladders, as well as four kidneys. Close to the lower margin of the livers, small bowel loops were observed, which were closely related, making it difficult to characterize whether there was a crossing between them from one fetus to another. Discussion: Although imperfect twinning is a rare condition, estimated at 1 in 75,000 births, its prenatal diagnosis is very important. It makes it possible to assess the fetal fusion site and its complexity to help define management and prognosis. Final Comments: Thus, the evaluation of fetuses with imperfect twinning is usually multidisciplinary, involving mainly radiologists, obstetricians, pediatricians, and pediatric surgeons, intending to start birth planning during pregnancy, including a place that has adequate conditions for receiving and properly handling these babies. 112083 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Hematological Alterations in a Patient with Congenital Heart Disease: Jacobsen Syndrome HELENA GUEDES DA ROCHA1, Estefany Karenine Rodriguez Casanova1, Caroline Engster da Silva1, Lais Bettoni1, Rafael Fabiano Machado Rosa1 (1) Universidade Federal de Ciencias da Saude de Porto Alegre - UFCSPA Background: Jacobsen syndrome is a chromosomal abnormality characterized by a deletion involving the long arm of chromosome 11 and is associated with different clinical findings. Objective: To report the case of a patient with Jacobsen syndrome secondary to a translocation of paternal origin, highlighting its relationship with congenital heart diseases. Results/Case Report: The patient, who is the second child of young parents, was born by cesarean delivery weighing 3500 g and with an Apgar score of 10 at the fifth minute. He had a history of surgery for correction of pyloric stenosis at 54 days of life. On physical examination, palpebral ptosis, right inguinal hernia, bilateral hallux valgus, clinodactyly of the 5th finger and syndactyly between the 2nd and 3rd pododactiles were observed. Echocardiography revealed an interventricular communication. The patient also had a history of epistaxis, ecchymosis and coagulation problems. He had a neuropsychomotor developmental delay that affected his school performance. In addition, the neurological evaluation found an attention deficit hyperactivity disorder. Computed tomography showed an epidermoid cyst in the skull. Audiometric evaluation revealed moderate sensorineural hearing loss in both ears. Karyotype showed a deletion of part of chromosome 11 (46, XY, del (11) (q23.1q25) ), compatible with the diagnosis of Jacobsen syndrome. The complementary examination of the father revealed the presence of a translocation between chromosomes 6 and 11. Conclusions: Patients with Jacobsen syndrome may present a multisystemic involvement, which demands a multidisciplinary approach. Special attention should be dedicated to congenital heart diseases, since they are one of the main causes of death in these patients. Heart defects are observed in 56% of the cases and usually require drug treatment and/or surgical correction. The interventricular communications, such as the one observed in our patient, are the most common cardiac malformations. All this is of great importance, since hematological alterations are also common, which may corroborate to an increase in morbidity and mortality of the patients. 112102 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Transthyretin Cardiac Amyloidosis Due to Homozygous Val142Ile Variant LUANA DIAS XAVIER1, Joao Paulo Dias Costa1, Julia Souza Diniz1, Emerson De Santana Santos1, Joselina Luzia Menezes Oliveira1 (1) Universidade Federal de Sergipe Introduction: Val142Ile, predominantly found among African descents, is the most common transthyretin (TTR) amyloidosis variant and predominantly develops a cardiomyopathy phenotype. Individuals with two variants in the TTR gene are extremely rare. They tend to manifest symptoms a mean of 10 years earlier than heterozygotes and it can be more severe. We report a Northeast Brazilian family with recurrence of homozygotes for Val142Ile due to consanguineous marriages. Case Report: A 77-year-old male was referred to cardiogenetics evaluation due to progressive heart failure whose symptoms started at the age of 70 and cardiac amyloidosis was suspected. He had asymmetrical septal hypertrophy and arrhythmia. Holter showed sporadic ventricular ectopia and supraventricular ectopia. An echocardiogram revealed restrictive cardiomyopathy and left ventricle hypertrophy. 99mTc-Pyrophosphate scintigraphy was also suggestive of TTR cardiac amyloidosis. His cardiac magnetic resonance imaging (MRI) showed ventricular septal hypertrophy, perfusion deficit in stress, and delayed myocardial enhancement. A molecular exam detected Val142Ile in heterozygosity. His ex-wife (who is also his cousin), a 74-year-old lady who was born from a consanguineous marriage (her parents were first-grade cousins too), is also affected. Cardiac MRI showed asymmetric apical hypertrophy, stress echocardiogram was negative for ischemia, and the genetic test showed she was homozygous for the Val142Ile variant. Their older son had sudden cardiac death at the age of 52. Their younger daughter, a 42-year-old female, has no cardiac involvement yet and she is also homozygous for the Val142Ile variant. All reported patients had bilateral carpal tunnel syndrome and no other neurological manifestation. Conclusion: The frequency of consanguineous marriages in Northeast Brazil is higher than in other regions, with rates as high as 6 to 12% in rural areas. Inbreeding has certainly contributed to the homozygosity in Val142Ile detected in two members of the family. Genetic counseling was provided to the family since early diagnosis may benefit affected members with the available treatments. 112204 Modality: E-Poster Scientific Initiation - Case Report Category: CONGENITAL AND PEDIATRIC CARDIOLOGY Ebstein Syndrome in Elderly Patient FELIPE SALIM HABIB BUHAMARA ALVES NASSER GURJAO1, Felipe Salim Habib Buhamara Alves Nasser Gurjao1, Bruna de Almeida Freixedelo1, Mateus Sousa Cavalcante1, Leandro Cordeiro Portela1, Dara Medeiros Mendes1, Vicente Lopes Montes Neto1 (1) Universidade Federal do Ceara - Campus Sobral Introduction: Ebstein's anomaly corresponds to a set of malformations centered around the tricuspid valve. This syndrome corresponds to the most common congenital heart disease of the tricuspid valve. The severity of symptoms depends primarily on age and the degree of insufficiency presented. The clinical spectrum is variable and can range from death in 50% of cases in newborn patients to a silent disease with symptoms appearing only after decades. Case Description: Male patient, 68 years, diagnosed with systemic arterial hypertension, type 2 diabetes and heart failure, since 2017, sought medical care at the Senador Carlos Jereissati Municipal Hospital on 04/18/2022 due to respiratory distress with progressive worsening for two days. He had BP: 70 x 40 mmHg, Capillary blood glucose: 180, RR: 30, HR: 111, T: 35.1degC and oxygen saturation: 85% in oxygenation of 15 L/min. Thus, due to the patient's serious condition and the lack of stabilization in the hospital of origin, a transfer to the North Regional Hospital was requested, where the patient was admitted in the early hours of the following day. At the time of admission, the patient was tachypneic, diffusely diminished universal vesicular murmurs with diffuse crackles. An electrocardiogram was performed which reported low voltage and atrial fibrillation. The patient was then hospitalized under the action of vasoactive drugs and oxygen therapy for better hemodynamic stabilization and search for the cause of heart failure decompensation. Laboratory tests and a transthoracic echocardiogram were requested. Among these tests, the echocardiogram, performed on 04/21/2022, showed a significant increase in the right chambers, with atrialization of the right ventricle and 31 mm inferior detachment of the tricuspid valve septal cusp of the tricuspid valve, adhered to the contractile right ventricular wall e decreased right ventricle contractile function, which indicates Ebstein Syndrome. Conclusion: Ebstein's anomaly corresponds to a complex and rare disease that mainly affects newborns with greater severity. Knowing the anatomical changes and cardiac physiology is essential for the correct approach to this condition. Health professionals should be alert to detect symptoms suggestive of heart failure and request tests for confirmation. As it is characterized as an insidious disease, the early diagnosis of this condition corresponds to a point of great importance for the proper management of the patient. 112241 Modality: E-Poster Scientific Initiation - Case Report Category: HEART FAILURE/CARDIOMYOPATHY/TRANSPLANT Peripartum Cardiomyopathy and the Hardships to Diagnose It: Case Report ANA ROBERTA DE SOUSA ARAUJO1, Beatriz Nunes Deseyvan Rodrigues2, Rayanne Carvalho Vasconcelos de Azevedo2, Ana Roberta de Sousa Araujo1 (1) FIMCA; (2) FIMCA Opening: The peripartum cardiomyopathy (PPCM) is a cardiac insufficiency secondary to systolic dysfunction of the left ventricle that affects women at the end of their pregnancy or even 6 months after giving birth. It has left ventricle ejection fraction (LVEF) < 45%, with a condition of dyspnea, fatigue and lower extremity edema (LEE). The risk factors include being an afro-descendant, multiparity, maternal old age and preeclampsia. Furthermore, it presents high and variable mortality rate, because it can be avoided with an early diagnosis and specific treatment. So, documenting PPCM is important, given that it often gets a late diagnosis. Thus, this study objectifies reporting the case of a woman diagnosed with PPCM 6 months after giving birth. Case Report: 33-year-old woman, brown, married, home secretary, no prior diseases, multiparous, no cardiomyopathies in previous gestations, developed preeclampsia in the fifth gestation, which was treated. Her delivery occurred after a hypertensive peak via cesarean, ceasing the hypertensive disturbances. 6 months of gestation passed, reported tiredness, dyspnea and an edema on the lower limbs, that extended itself to the abdomen. There was a diagnosis of cardiomegaly, and with the condition getting worse, she was hospitalized in an intensive Therapy unit. It was identified a 120/94 mmHg blood pressure, pulmonary noises with sparse hisses, high troponin I in the laboratory tests and hepatomegaly in the total abdomen ultrasound. In the Echocardiogram, it was verified a LVEF of 30, left ventricle dilated, diffuse hypokinesia, sharp systolic dysfunction, right ventricle with moderate increase, significant aortic regurgitation and moderate mitral. In the cardiogram, it was observed sinus tachycardia (FC > 99 bpm), probable left ventricular hypertrophy and long QT interval. Hence, after clinical analyses the patient was diagnosed with PPCM, it was prescribed atorvastatin, carvedilol and enalapril. With a bad prognosis, the patient finds itself admitted to the transplant center. Conclusion: Therefore, PPCM being a hard to diagnose disease, probable to adversely evolve, might be necessary to perform a transplant, as in the discussed case. However, controlling the appearance of signs and specific symptoms, besides doing early diagnostic tests, can effectively avoid complications. So, it's indispensable to increase the scientific knowledge to improve the prognosis. Competing Interests The authors have no competing interests to declare. |
PMC10000336 | Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.34767 Ophthalmology Are YouTube Videos on the Treatment of Macular Holes Useful for Patients? Muacevic Alexander Adler John R Sabanci Senol 1 Erol Muhammet Kazim 1 Gedik Birumut 2 Yaprak Lutfiye 1 Suren Elcin 1 1 Ophthalmology, Antalya Training and Research Hospital, Antalya, TUR 2 Ophthalmology, Antalya Serik State Hospital, Antalya, TUR Birumut Gedik [email protected] 8 2 2023 2 2023 15 2 e347678 2 2023 Copyright (c) 2023, Sabanci et al. 2023 Sabanci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from Objective In this study, we aimed to assess the effectiveness and quality of the YouTube videos for patients regarding the treatment of macular holes. Materials and methods The quality and effectiveness of the videos on macular hole treatment on YouTube were evaluated using the DISCERN, global quality score (GQS), Journal of the American Medical Association (JAMA), and usefulness index scoring systems. Results The median DISCERN score of 100 videos included in the study was 18 (range: 15-73), the median JAMA score was 3 (range: 0-4), the median global quality score was 1 (range: 1-5), and the median usefulness index score was 1 (range: 0-5). The JAMA scores of the videos uploaded by non-clinicians were found to be significantly lower than those of the videos uploaded by clinicians (p<0.001). However, the daily viewing rate and the number of comments and likes for the videos uploaded by non-clinicians were found to be significantly higher than those for the videos uploaded by clinicians (p<0.003). Conclusion Based on our findings, while all of the beneficial macular hole videos on YouTube were published by clinicians, the majority of them are not really helpful to patients. macular hole youtube video jama discern The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. pmcIntroduction A macular hole is a retinal disorder that is usually seen in people of advanced ages and it affects the central vision. Even though the majority of them are largely idiopathic, secondary causes can occasionally be involved . Although the treatment method for a macular hole is determined by its degree, a vitrectomy is typically employed. Other therapeutic options include intravitreal injection of medications such as ocriplasmin. With various surgical techniques devised in the last several years, vitrectomy has seen a big improvement in functional success and a large improvement in anatomical success . The internet has become a major source of medical information in recent years, and nearly all patients use the internet to research their complaints and illnesses. YouTube is among the most well-known of these sites. Of note, 79% of internet users have a YouTube account, and with 2.3 billion monthly active users, over one billion hours of video viewing, and over 720,000 hours of video posting each day, the rate at which YouTube is used has risen astronomically over the past few years . Also, YouTube has established itself as a very popular source of health-related information. However, the ease with which videos may be uploaded to YouTube and the fact that anybody, expert or not, is able to do so raise concerns about the validity of the material and the potential for spreading misinformation. As a response to these concerns, studies that assess the validity and substance of health-related videos posted on social media platforms have started to appear in recent years . In this study, we assessed the YouTube videos regarding macular hole therapy for their quality, dependability, and level of benefit to patients. Materials and methods On December 22, 2021, the first 120 videos were seen after signing out of the YouTube site and typing in "macular hole therapy for patients." The study included videos in English that are more than a minute long. Videos that were duplicated, unrelated to macular holes, without audio or subtitles, less than one minute in length, not in English, or those in which comments had been deleted by the uploader were excluded from our study. The number of times the video has been viewed, its length, its age (from the time it was uploaded until January 22, 2022), the number of likes and comments it has received, who uploaded it (a patient, a healthcare professional, a hospital or academic institution, a commercial health channel), its purpose (clinical information, treatment, and postoperative period), and its content (scientific, patient information, patient experience), were all evaluated in the study. The utility level of the videos was also evaluated by using the DISCERN, global quality score (GQS), Journal of the American Medical Association (JAMA), and usefulness index scoring systems (Tables 1-4). Table 1 DISCERN scoring system Section 1 What is investigated? Is the publication reliable? No Partially Yes 1 Are the aims clear? 1 2-3 4-5 2 Does it achieve its aims? 1 2-3 4-5 3 Is it relevant? 1 2-3 4-5 4 Is it clear what sources of information were used to compile the publication (other than the author or producer)? 1 2-3 4-5 5 Is it clear when the information used or reported in the publication was produced? 1 2-3 4-5 6 Is it balanced and unbiased? 1 2-3 4-5 7 Does it provide details of additional sources of support and information? 1 2-3 4-5 8 Does it refer to areas of uncertainty? 1 2-3 4-5 Section 2 How good is the quality of information regarding treatment choices? 9 Does it describe how each treatment works? 1 2-3 4-5 10 Does it describe the benefits of each treatment? 1 2-3 4-5 11 Does it describe the risks of each treatment? 1 2-3 4-5 12 Does it describe what would happen if no treatment is used? 1 2-3 4-5 13 Does it describe how the treatment choices affect the overall quality of life? 1 2-3 4-5 14 Is it clear that there may be more than 1 possible treatment choice? 1 2-3 4-5 15 Does it provide support for shared decision-making? 1 2-3 4-5 Section 3 Overall rating of the publication 16 Based on the answers to all of these questions, rate the overall quality of the publication as a source of information about treatment choices 1 2-3 4-5 1: Low 2-3: Moderate 4-5: High Table 2 Usefulness score criteria Usefulness score Score criteria Not mentioned Mentioned Definition 0 1 Indication 0 1 Procedure involved 0 1 Complication 0 1 Prognosis-survival 0 1 Table 3 JAMA score criteria JAMA: Journal of the American Medical Association JAMA score Authorship: authors and contributors, their affiliations, and relevant credentials should be provided (0 or 1 point) Attribution: references and sources for all content should be listed clearly, and all relevant copyright information should be noted (0 or 1 point) Disclosure: website "ownership" should be prominently and fully disclosed, as should any sponsorship, advertising, underwriting, commercial funding arrangements or support, or potential conflicts of interest (0 or 1 point) Currency: dates when content was posted and updated should be indicated (0 or 1 point) Table 4 Global quality scoring system Global quality score 1 - Poor quality, very unlikely to be of any use to patients 2 - Poor quality but some information present, of very limited use to patients 3 - Suboptimal flow, some information covered but important topics missing, somewhat useful to patients 4 - Good quality and flow, most important topics covered, useful to patients 5 - Excellent quality and flow, highly useful to patients The DISCERN system, which has three parts and 16 questions that are scored on a scale of 1 to 5, is used to assess the content, balance, and clarity of each given publication's arguments. The first eight questions focus on dependability, the next seven provide treatment information, and the last question assesses overall quality. Scores for the videos range from 16 to 75, categorized as follows: 63-75: excellent, 51-62: good, 39-50: fair, 27-38: poor, and 16-26: extremely poor . Another rating system, JAMA, rates the validity of online health resources on a scale of 0 to 1, taking into consideration the authors' clarity, references and citations, declaration of any financial or other relationships with commercial interests, timeliness, and the date the data was posted . Another grading method, the global quality score, gives a score between 1 and 5 depending on the uploaded video's content, quality, and chance of helping patients. Another rating method is the video usefulness index, which gives points to materials based on the disease diagnosis, treatment indication, technique, prognosis, and consequences. Each item receives 1 point in this scoring system, which is then summed up. Scores of 0 and 1 are seen as having limited value for patients since they provide little information and video material. A score of 2-3 shows that the information and substance are of decent quality, but the patients are still not sufficiently educated. A score of 4-5 indicates that the content is sufficiently capable of educating patients and the information is of excellent quality and substance . Statistical analysis For descriptive statistics, mean +- standard deviation (SD) was used to present continuous data with normal distribution. The median with minimum-maximum values was applied for continuous variables without normal distribution. Numbers and percentages were used for categorical variables. The Shapiro-Wilk, Kolmogorov-Smirnov, and Anderson-Darling tests were used to analyze the normal distribution of the numerical variables. The Mann-Whitney U test was employed to compare two independent groups where numerical variables had no normal distribution. The Kruskal-Wallis H test was used to compare more than two independent groups where numerical variables had no normal distribution. The Dwass-Steel-Critchlow-Fligner test was utilized to evaluate differences between the groups if the non-parametric tests were applied. The Pearson Chi-Square and Fisher's exact tests were used to compare the differences between categorical variables in 2x2 tables. The Fisher-Freeman Halton test was used in RxC tables. Spearman correlation coefficients were calculated to analyze the relationships between the videos' descriptive statistics and characteristics. Jamovi (Version 2.2.5.0) and JASP (Version 0.16.1) were used for statistical analysis. A p-value of 0.05 was considered statistically significant. Results Of the 120 videos we watched, 100 were included in the study; nine videos unrelated to the macular hole, four videos without sound, three duplicated videos, two videos shorter than one minute, and two non-English videos were excluded from the study. Descriptive statistics are presented in Table 5. The median length of the videos was 4.2 minutes, ranging from one to 136.2 minutes. The majority (60.0%) were less than five minutes in length. They received a median of 1889.5 views with a viewing rate of 1.6 per day. The median number of "likes" was 16, ranging from 0 to 491. Table 5 Data on the length, number of views, comments, and likes related to the videos Variables Values (n=100) Video length, minutes, median (range) 4.2 (1-136.2) Groups by video length, n (%) <5 minutes 60 (60) 5-10 minutes 22 (22) >=10 minutes 18 (18) Days since upload, median (range) 821 (30-5091) Number of views, median (range) 1189.5 (13-95938) Daily viewing rate, median (range) 1.6 (0-54.8) Number of comments, median (range) 2 (0-272) Number of likes, median (range) 16 (0-491) Video characteristics are shown in Table 6. Healthcare professionals uploaded the majority of the videos (93%). Grouping based on the upload source revealed that healthcare professionals (40%), commercial health channels (28%), and hospital or academic institutions (25%) were the most frequent sources of the videos. The purpose of the videos was related to clinical information and treatment in most cases (Table 6). More than half of the videos (63%) had a scientific context. The calculations regarding the total scores of the different quality metrics are detailed in Table 6. Regarding the usefulness score, more than half of the videos (67%) scored 0-1. Table 6 Data on the authorship, upload source, purpose, and content of the videos JAMA: Journal of the American Medical Association Variables Values (n=100) Personal source of authorship, n (%) Healthcare professional 93 (93) Non-healthcare individual users 7 (7) Upload source, n (%) Healthcare professional 40 (40) Hospital/academic institution 25 (25) Commercial health channel 28 (28) Patient 7 (7) Purpose, n (%) Clinical information 8 (8) Treatment 62 (62) Clinical information and treatment 26 (26) Postoperative period 4 (4) Content, n (%) Scientific 63 (63) Patient information 29 (29) Patient experience 8 (8) DISCERN score, median (range) 18 (15-73) JAMA score, median (range) 3 (1-4) Global quality score, median (range) 1 (1-5) Usefulness score, median (range) 1 (0-5) Usefulness score categories, n (%) 0-1 67 (67) 2-3 21 (21) 4-5 12 (12) There were significant differences between the descriptive statistics and characteristics of the videos uploaded by healthcare professionals and those of the videos uploaded by non-healthcare users (Table 7). The videos uploaded by non-healthcare individual users were significantly longer (p=0.002), had more views (p=0.003), comments (p<0.001), and "likes (p<0.001), and had a higher rate of daily viewing (p=0.001). Table 7 Comparison of the data on videos based on the source of authorship *Mann-Whitney U test; **Pearson Chi-square or Fisher-Freeman-Halton test JAMA: Journal of the American Medical Association Variables Source of authorship P-value Healthcare professionals (n=93) Non-healthcare users (n=7) Video length, minutes, median (range) 4.0 (1.0-136.2) 13.1 (5.2-16.4) 0.002* Groups by video length, n (%) <5 minutes 60 (64.5) 0 (0) <0.001** 5-10 minutes 21 (22.6) 1 (14.3) >=10 minutes 12 (12.9) 6 (85.7) Days since upload, median (range) 821 (30-5091) 790 (274-1701) 0.766* Number of views, median (range) 969 (13-95938) 7514 (2061-29775) 0.003* Daily viewing rate, median (range) 1.2 (0-54.8) 12.6 (2.6-34.1) 0.001* Number of comments, median (range) 1 (0-254) 54 (11-272) <0.001* Number of likes, median (range) 14 (0-491) 130 (50-419) <0.001* Upload source, n (%) Healthcare professional 40 (43) 0 (0) <0.001** Hospital or academic institution 25 (26.9) 0 (0) Commercial health channel 28 (30.1) 0 (0) Patient 0 (0) 7 (100) Purpose, n (%) Clinical information 6 (6.5) 2 (28.6) 0.038** Treatment 60 (64.5) 2 (28.6) Clinical information and treatment 24 (25.8) 2 (28.6) Postoperative period 3 (3.2) 1 (14.3) Content, n (%) Scientific 63 (67.7) 0 (0) <0.001** Patient information 29 (31.2) 0 (0) Patient experience 1 (1.1) 7 (100) DISCERN score, median (range) 17 (15-73) 21 (16-29) 0.458* JAMA score, median (range) 3 (1-4) 2 (1-2) <0.001* Global quality score, median (range) 1 (1-5) 2 (1-3) 0.138* Usefulness score, median (range) 1 (0-5) 2 (0-3) 0.698* Usefulness score categories, n (%) 0-1 64 (68.8) 3 (42.9) 0.074** 2-3 17 (18.3) 4 (57.1) 4-5 12 (12.9) 0 (0) We detected significant differences regarding the upload source, purpose, and content of the videos (p<0.05) (Table 7). The scores of the quality metrics (DISCERN, global quality score, and usefulness score) were similar between the groups (p=0.458, p=0.138, p=0.698, respectively) (Table 7). The videos uploaded by non-healthcare users had a lower median JAMA score than those by healthcare professionals (p<0.001). Table 8 presents a comparative analysis of the descriptive statistics and characteristics of the videos according to the upload sources. There were significant differences between the groups (p<0.05). The length of the videos uploaded by patients was significantly longer than those by healthcare professionals (p=0.033), hospital or academic institutions (p=0.008), and healthcare channels (p=0.014). We detected significant differences in the number of views and daily view rates between the videos by patients and those by healthcare professionals (p=0.026 and p=0.002, respectively) and healthcare channels (p=0.016 and p=0.009, respectively). The viewing rate per day was significantly higher for videos by patients than those uploaded by hospitals or academic institutions (p=0.049). The number of comments and "likes" for the videos uploaded by patients was significantly higher than for those uploaded by healthcare professionals (p<0.001 and p=0.001, respectively), hospitals/academic institutions (p<0.001 and p=0.005, respectively), and healthcare channels (p<0.001 and p<0.001, respectively). Table 8 Comparison of the data on videos based on the upload source *Kruskal-Wallis H test; **Pearson Chi-square or Fisher-Freeman-Halton test JAMA: Journal of the American Medical Association Variables Upload source P-value Healthcare professionals (n=40) Hospitals/academic institutions (n=25) Healthcare channels (n=28) Patients (n=7) Video length, minutes, median (range) 4.8 (1-136.2) 3.2 (1-31.2) 3.1 (1-58) 13.1 (5.2-16.4) 0.005* Groups by video length, n (%) <5 minutes 20 (50) 19 (76) 21 (75) 0 (0) <0.001** 5-10 minutes 15 (37.5) 3 (12) 3 (10.7) 1 (14.3) >=10 minutes 5 (12.5) 3 (12) 4 (14.3) 6 (85.7) Days since upload, median (range) 896.5 (145-5091) 761 (30-3440) 852 (31-4352) 790 (274-1701) 0.732* Number of views, median (range) 777 (13-82138) 1214 (25-64531) 876 (42-95938) 7514 (2061-29775) 0.024* Daily viewing rate, median (range) 1.1 (0-19.3) 1.7 (0.1-54.8) 1 (0-25.2) 12.6 (2.6-34.1) 0.004* Number of comments, median (range) 2.5 (0-254) 0 (0-30) 1 (0-65) 54 (11-272) <0.001* Number of likes, median (range) 14.5 (0-168) 16 (0-491) 10.5 (0-78) 130 (50-419) 0.001* Source of authorship, n (%) Healthcare professionals 40 (100) 25 (100) 28 (100) 0 (0) <0.001** Non-healthcare individual users 0 (0) 0 (0) 0 (0) 7 (100) Purpose, n (%) Clinical information 0 (0) 4 (16) 2 (7.1) 2 (28.6) <0.001** Treatment 33 (82.5) 9 (36) 18 (64.3) 2 (28.6) Clinical information and treatment 7 (17.5) 12 (48) 5 (17.9) 2 (28.6) Postoperative period 0 (0) 0 (0) 3 (10.7) 1 (14.3) Content, n (%) Scientific 34 (85) 9 (36) 20 (71.4) 0 (0) <0.001** Patient information 6 (15) 15 (60) 8 (28.6) 0 (0) Patient experience 0 (0) 1 (4) 0 (0) 7 (100) DISCERN score, median (range) 16 (15-69) 29 (16-64) 17 (16-73) 21 (16-29) 0.004* JAMA score, median (range) 3 (1-4) 3 (1-3) 3 (1-4) 2 (1-2) 0.004* Global quality score, median (range) 1 (1-4) 3 (1-5) 1 (1-4) 2 (1-3) 0.001* Usefulness score, median (range) 1 (0-5) 1 (0-5) 1 (0-4) 2 (0-3) 0.165* Usefulness score categories, n (%) 0-1 29 (72.5) 13 (52) 22 (78.6) 3 (42.9) 0.048** 2-3 8 (20) 5 (20) 4 (14.3) 4 (57.1) 4-5 3 (7.5) 7 (28) 2 (7.1) 0 (0) The DISCERN score for the videos uploaded by hospitals or academic institutions was significantly higher than for those uploaded by healthcare professionals (p=0.007) and healthcare channels (p=0.049). JAMA scores for videos by patients were significantly lower than for videos by healthcare professionals (p=0.002), hospitals or academic institutions (p=0.015), and healthcare channels (p=0.024). Global quality scores for videos uploaded by hospitals or academic institutions were significantly higher than for those by healthcare professionals (p=0.007) and healthcare channels (p=0.017). Although the median value of the usefulness score was similar between the groups (p=0.165), the categories based on this score revealed significant differences (p=0.048) (Table 8). Although the median length of the videos according to the usefulness score categories was similar (p=0.321), we detected significant differences between the categories regarding the duration of the videos and the usefulness score categories (p=0.001). The descriptive statistics were similar between the usefulness score categories (p>0.05) (Table 9). Table 9 Comparison of the data on videos based on usefulness score categories *Kruskal-Wallis H test; **Pearson Chi-square or Fisher-Freeman-Halton test JAMA: Journal of the American Medical Association Variables Usefulness score categories P-value 0-1 (n=67) 2-3 (n=21) 4-5 (n=12) Video length, minutes, median (range) 4 (1-58) 4.3 (1-136.2) 4.3 (1.4-56.2) 0.321* Groups by video length, n (%) <5 minutes 42 (62.7) 11 (52.4) 7 (58.3) 0.001** 5-10 minutes 20 (29.9) 1 (4.8) 1 (8.3) >=10 minutes 5 (7.5) 9 (42.9) 4 (33.3) Days since upload, median (range) 897 (31-5091) 641 (152-3011) 716.5 (30-2861) 0.114* Number of views, median (range) 1574.0 (13-95938) 491 (39-21458) 720.5 (25-64531) 0.233* Daily viewing rate, median (range) 1.7 (0.1-54.8) 0.9 (0-34.1) 2 (0.1-32) 0.448* Number of comments, median (range) 2 (0-254) 0 (0-272) 0.5 (0-30) 0.608* Number of likes, median (range) 18 (0-158) 8 (0-419) 8 (1-491) 0.349* Purpose, n (%) Clinical information 7 (10.4) 1 (4.8) 0 (0) <0.001** Treatment 50 (74.6) 11 (52.4) 1 (8.3) Clinical information and treatment 7 (10.4) 8 (38.1) 11 (91.7) Postoperative period 3 (4.5) 1 (4.8) 0 (0) Content, n (%) Scientific 49 (73.1) 9 (42.9) 5 (41.7) 0.009** Patient information 14 (20.9) 8 (38.1) 7 (58.3) Patient experience 4 (6) 4 (19) 0 (0) DISCERN score, median (range) 16 (15-32) 29 (16-53) 47.5 (30-73) <0.001* JAMA score, median (range) 3 (1-4) 3 (1-4) 3.0 (2-4) 0.697* Global quality score, median (range) 1 (1 -3) 3 (1-4) 4.0 (1-5) <0.001* There were significant differences in the distribution of the categories based on the purpose and content of the videos between the groups (p<0.05) (Table 9). The comparison of the JAMA scores revealed no significant differences (p=0.697). However, the videos with a usefulness score of 4-5 had significantly higher values of the DISCERN and global quality score than those with a score of 2-3 (p<0.001 and p=0.001, respectively) and a score of 0-1 (p<0,001 and p<0.001, respectively). We detected significant differences in the values of the DISCERN and global quality scores between the usefulness scores of 2-3 and 0-1 (p<0.001 and p<0.001, respectively) (Table 9). The results of the correlation analysis of the descriptive statistics and video characteristics are detailed in Table 10. The DISCERN score positively correlated with the global quality score (r=0.796, p<0.001) and the usefulness score (r=0.823, p<0.001). There was a positive correlation between the global quality score and the usefulness score (r=0.690, p<0.001). Table 10 Data on correlations between various aspects of the videos Spearman's rho correlation coefficient JAMA: Journal of the American Medical Association Variables Video length, minutes Days since upload Number of views Daily viewing rate Number of comments Number of likes DISCERN score JAMA score Global quality score Days since upload r 0.000 -- P-value 0.994 -- Number of views r 0.138 0.555 -- P-value 0.171 <0.001 -- Daily viewing rate r 0.180 0.078 0.845 -- P-value 0.074 0.440 <0.001 -- Number of comments r 0.221 0.139 0.582 0.610 -- P-value 0.027 0.169 <0.001 <0.001 -- Number of likes r 0.167 0.179 0.774 0.801 0.712 -- P-value 0.097 0.076 <0.001 <0.001 <0.001 -- DISCERN score r 0.102 -0.214 -0.061 0.056 -0.215 -0.112 -- P-value 0.311 0.033 0.544 0.581 0.031 0.267 -- JAMA score r -0.077 -0.081 -0.272 -0.238 -0.327 -0.299 0.109 -- P-value 0.444 0.422 0.006 0.017 <0.001 0.002 0.279 -- Global quality score r -0.088 -0.125 0.001 0.085 -0.101 -0.056 0.796 -0.008 -- P-value 0.382 0.214 0.990 0.400 0.320 0.583 <0.001 0.938 -- Usefulness score r 0.148 -0.221 -0.125 -0.009 -0.142 -0.172 0.823 0.149 0.690 P-value 0.141 0.027 0.216 0.930 0.157 0.086 <0.001 0.139 <0.001 Discussion Today, the internet has become an almost indispensable tool in our everyday lives. The internet, which we utilize to research any topic under the sun, is commonly used for medicine-related search/research as well. One of the social media sites, YouTube, is now the second-most-used search resource after Google . The fact that YouTube is widely utilized, the ease with which to submit videos on it, and that it is free have made it a gathering place for both people seeking knowledge and those wanting to share it. All of these carry some dangers as well as potential benefits. One of these risks would be that people could be given inaccurate or incomplete information by others who lack appropriate knowledge or who have vested personal or professional interests. According to Sahin et al., one-third of the YouTube videos on retinopathy of prematurity were erroneous and could have negative effects . Owing to these factors, some people might decide not to get certain therapies, while others may demand unrealistically high results. For the reasons explained above, there has been an increase in recent years in the studies on the validity, impartiality, content, and quality of health details available on YouTube . Our review of the literature revealed scarce research analyzing the caliber, substance, and dependability of YouTube videos related to macular holes. We reviewed YouTube videos regarding treatment for macular holes for the purpose of this study. Relevant videos were graded in this study based on the DISCERN, JAMA, global quality score, and usefulness scoring index. We had to use the median value rather than the mean value since vastly different values were obtained within the results of each scoring system. The median scores for DISCERN, JAMA, and usefulness and global quality scores were assessed to be 18, 3, 1, and 1, respectively, in this study. Clinical videos submitted by nonphysicians had an average JAMA score significantly lower than clinical videos uploaded by physicians. The JAMA score offers important details on the dependability of the submitted video as it assesses the video's origin, the person who shot it, any possible sponsors or financial ties, the video's relevance, and references . Therefore, their high JAMA scores lead us to conclude that clinical videos uploaded are more trustworthy. Between clinicians and non-clinicians, the mean scores related to other scoring systems were not significant (global quality score, usefulness index, DISCERN) . The median DISCERN score in this study was 18, which was shown to be far lower than in similar investigations on other individuals. We may infer that this is because most videos regarding macular holes are scientific in nature and only discuss surgery, skipping over symptoms, causes, types of therapy, side effects, and prognosis. This disease is less widespread than other illnesses, which means less commercial return, as well as a low number of physicians interested in this issue. Due to these reasons, macular hole videos may have been uploaded mostly for scientific purposes rather than informing patients. The content and purpose of the videos produced by healthcare professionals and those uploaded by non-healthcare professionals were found to be significantly different (p<0.05). The highest DISCERN score among the videos uploaded by non-clinicians was 29. This was due to the fact that patients frequently recorded videos explaining why they underwent surgery and the recommended head posture following surgery. Only three of the videos analyzed were found to have DISCERN scores of 63 or above and very high content standards, and these were all submitted by physicians. Only five videos in the review met all the usefulness score criteria (indication, description, surgical technique, complication, and prognosis), and all of these videos were posted by clinicians. Based on our analysis of who uploaded the videos reviewed in other studies, we observe that there is a difference between clinicians and non-clinicians, but this difference is more pronounced in our study . This could be attributed to the fact that the macular hole is less common than the other reviewed subjects and subsequently less popular. Another explanation could be that macular holes are typically diagnosed in elderly patients, who are also less likely to utilize social media to describe their experiences. In this study, it was shown that videos submitted by non-clinicians had more views and a higher daily view rate (Table 7). We may explain this by pointing out that since they do not use medical terminology, persons with the same ailment tend to be more inquisitive about what others are going through. The fact that surgical videos for scientific purposes make up the majority of the videos produced by physicians regarding macular holes, and that some of them contain lengthy videos in the form of seminars, might be a factor in the dearth of views. Based on an analysis of the number of comments and likes, it was found that the videos uploaded by non-clinicians obtained more comments and likes than the videos uploaded by clinicians (p<0.001). This is explained by the fact that videos with more viewership receive more likes and comments. Since YouTube hides the number of dislikes, it was not possible to calculate the number of dislikes or the viewer interaction index in this study. Based on the above-mentioned findings, there are several videos concerning macular holes on YouTube that have been posted by medical professionals, healthcare organizations (hospitals and academic institutions), commercial health channels, and patients. Most of these videos were produced for scientific purposes, and few of them are actually helpful to patients. It has been shown that even the videos uploaded by professionals do not go into adequate detail regarding available treatments, side effects, and prognosis. Most videos released in recent years have been about treating macular holes. It has been observed that some videos on advancements in science and surgery have been produced. There is a remarkable number of videos discussing the inverted flap procedure, which is used to repair big and refractory macular holes. It appears that individuals will increasingly use YouTube in the coming years to obtain knowledge on health and healthcare, just as they do with every other subject. Conclusions This is the first study to analyze the caliber, substance, and dependability of YouTube videos related to macular holes in the literature. Although YouTube videos could be incredibly beneficial for many, they could also have many negative effects. The quality of videos released on sensitive and significant subjects like healthcare is crucial. Clinicians should properly describe the disease symptoms, when the treatment will begin, any potential complications, and the potential benefits of the therapy in the video recordings they publish to educate the public without regard for profit. In order to inform people more thoroughly and objectively, it will be beneficial for specialists to rigorously review health-related videos before they are uploaded to YouTube. Human Ethics Animal Ethics The authors have declared that no competing interests exist. Consent was obtained or waived by all participants in this study Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. References 1 Macular hole Surv Ophthalmol Ho AC Guyer DR Fine SL 393 416 42 1998 9548570 2 Rates of reoperation and retinal detachment after macular hole surgery Ophthalmology Vaziri K Schwartz SG Kishor KS Fortun JA Moshfeghi AA Smiddy WE Flynn HW Jr 26 31 123 2016 26505804 3 How Many People Use YouTube in 2022 2 2023 7 2021 [New Data] 2022 4 Are YouTube videos useful in informing patients about keratoplasty? Semin Ophthalmol Kalayci M Cetinkaya E Suren E Yigit K Erol MK 469 474 36 2021 33617416 5 Toward automated assessment of health web page quality using the DISCERN instrument J Am Med Inform Assoc Allam A Schulz PJ Krauthammer M 481 487 24 2017 27707819 6 Assessing, controlling, and assuring the quality of medical information on the Internet: caveant lector et viewor-let the reader and viewer beware JAMA Silberg WM Lundberg GD Musacchio RA 1244 1245 277 1997 9103351 7 Is the YouTubeTM an useful source of information on oral leukoplakia? Oral Dis Kovalski LN Cardoso FB D'Avila OP Correa AP Martins MA Martins MD Carrard VC 1897 1905 25 2019 31332880 8 Meet the 7 most popular search engines in the world March 3 2 2023 Meet the 7 Most 2023 9 YouTube as a source of information in retinopathy of prematurity Ir J Med Sci Sahin A Sahin M Turkcu FM 613 617 188 2019 30238185 10 YouTube videos in the English language as a patient education resource for cataract surgery Int Ophthalmol Bae SS Baxter S 1941 1945 38 2018 28849436 11 Medical YouTube videos and methods of evaluation: literature review JMIR Med Educ Drozd B Couvillon E Suarez A 0 4 2018 12 YouTube as a source of information about retinitis pigmentosa Eye (Lond) Guthrie G Davies RM Fleming CK Browning AC 499 500 28 2014 24434660 13 YouTube as a source of information on neurosurgery World Neurosurg Samuel N Alotaibi NM Lozano AM 394 398 105 2017 28599904 |
PMC10000338 | Pediatr Res Pediatr Res Pediatric Research 0031-3998 1530-0447 Nature Publishing Group US New York 36899124 2527 10.1038/s41390-023-02527-z Population Study Article Neonatal outcomes of maternal SARS-CoV-2 infection in the UK: a prospective cohort study using active surveillance Ali Shohaib 1 Mactier Helen 2 Morelli Alessandra 3 Hurd Madeleine 3 Placzek Anna 3 Knight Marian 3 Ladhani Shamez N. 4 Draper Elizabeth S. 5 Sharkey Don 6 Doherty Cora 7 Kurinczuk Jennifer J. 3 Quigley Maria A. 3 Gale Chris [email protected] 8 1 grid.7445.2 0000 0001 2113 8111 School of Public Health, Faculty of Medicine, Imperial College London, London, UK 2 grid.8756.c 0000 0001 2193 314X Princess Royal Maternity and the University of Glasgow, Glasgow, UK 3 grid.4991.5 0000 0004 1936 8948 NIHR Policy Research Unit in Maternal and Neonatal Health and Care, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK 4 grid.264200.2 0000 0000 8546 682X Paediatric Infectious Diseases and Vaccinology, St. George's University of London, London, UK 5 grid.9918.9 0000 0004 1936 8411 Department of Health Sciences, Centre for Medicine, University of Leicester, University Road, Leicester, UK 6 grid.4563.4 0000 0004 1936 8868 Centre for Perinatal Research, School of Medicine, University of Nottingham, Nottingham, UK 7 grid.241103.5 0000 0001 0169 7725 University Hospital of Wales, Cardiff, UK 8 grid.7445.2 0000 0001 2113 8111 School of Public Health, Faculty of Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Road, London, SW10 9NH UK 10 3 2023 10 3 2023 2023 94 3 12031208 21 7 2022 25 1 2023 30 1 2023 (c) The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Background Newborns may be affected by maternal SARS-CoV-2 infection during pregnancy. We aimed to describe the epidemiology, clinical course and short-term outcomes of babies admitted to a neonatal unit (NNU) following birth to a mother with confirmed SARS-CoV-2 infection within 7 days of birth. Methods This is a UK prospective cohort study; all NHS NNUs, 1 March 2020 to 31 August 2020. Cases were identified via British Paediatric Surveillance Unit with linkage to national obstetric surveillance data. Reporting clinicians completed data forms. Population data were extracted from the National Neonatal Research Database. Results A total of 111 NNU admissions (1.98 per 1000 of all NNU admissions) involved 2456 days of neonatal care (median 13 [IQR 5, 34] care days per admission). A total of 74 (67%) babies were preterm. In all, 76 (68%) received respiratory support; 30 were mechanically ventilated. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy. Twenty-eight mothers received intensive care, with four dying of COVID-19. Eleven (10%) babies were SARS-CoV-2 positive. A total of 105 (95%) babies were discharged home; none of the three deaths before discharge was attributed to SARS-CoV-2. Conclusion Babies born to mothers with SARS-CoV-2 infection around the time of birth accounted for a low proportion of total NNU admissions over the first 6 months of the UK pandemic. Neonatal SARS-CoV-2 was uncommon. Study registration ISRCTN60033461; protocol available at Impact Neonatal unit admissions of babies born to mothers with SARS-CoV-2 infection comprised only a small proportion of total neonatal admissions in the first 6 months of the pandemic. A high proportion of babies requiring neonatal admission who were born to mothers with confirmed SARS-CoV-2 infection were preterm and had neonatal SARS-CoV-2 infection and/or other conditions associated with long-term sequelae. Adverse neonatal conditions were more common in babies whose SARS-CoV-2-positive mothers required intensive care compared to those whose SARS-CoV-2-positive mothers who did not. issue-copyright-statement(c) International Pediatric Research Foundation, Inc 2023 pmcIntroduction Although serious infection with SARS-CoV-2 is uncommon in children, maternal SARS-CoV-2 infection around the time of birth is associated with adverse outcomes, including preterm birth1,2 and neonatal infection.3-5 Swedish data demonstrate a higher risk of preterm birth, neonatal unit (NNU) admission and neonatal respiratory conditions following birth to a mother with SARS-CoV-2 at any time in pregnancy.6 Although studies show adverse pregnancy outcomes increased in those mothers with severe/critical disease,7 only limited data describe neonatal clinical courses and outcomes. Accumulating data indicate that the Alpha and Delta variants of SARS-CoV-2 may lead to more severe maternal COVID-19;1 for comparative purposes, it is important to establish neonatal impacts of the initial wave of predominantly 'wildtype' SARS-CoV-2 infection. We aimed to describe the presentation, clinical course and short-term outcomes of babies born in the first wave of the pandemic to a mother with confirmed SARS-CoV-2 infection within 7 days of birth and who required NNU admission. Neonatal outcomes were examined by the severity of maternal COVID-19. Methods Study design and procedures This was a national prospective cohort study using the British Paediatric Surveillance Unit (BPSU).8 From 1 April 2020, senior paediatricians in all 155 hospital trusts and health boards with their associated 190 NNUs in the UK received a weekly electronic BPSU reporting card asking them to notify any babies born to mothers with laboratory-confirmed SARS-CoV-2 infection in the 7 days before or after birth, and who required admission to an NNU between 1 March 2020 to 30 August 2020. This did not include routine newborn care provided on the postnatal ward by neonatal health professionals. An additional monthly card asked for confirmation both that all eligible babies had been reported and that zero reports were accurate (active negative surveillance). To maximise case ascertainment, the UK Obstetric Surveillance System (UKOSS) study of COVID-19 admission in pregnancy was also used to identify and link babies born to women with laboratory-confirmed SARS-CoV-2 infection using hospital site, date and time of delivery. Following a BPSU report, notifying clinicians were asked to complete a data collection form with details of the pregnancy, baby characteristics, neonatal management and outcomes. Data collection was supported by hospital-based research nurses from the UK's National Institute of Health Research (NIHR) Clinical Research Network following the study's adoption as an urgent public health priority study. Cases identified were linked to routinely recorded neonatal clinical data held in the National Neonatal Research Database (NNRD) to describe neonatal treatments, clinical course and outcomes.8 Neonatal deaths were cross-checked with national perinatal mortality surveillance data from the Mother and Babies, Reducing Risk through Audits and Confidential Enquires across the UK (MBRRACE-UK) collaboration.9 Neonatal SARS-CoV-2 infection was cross-checked with national testing data from public health organisations as described previously.4 UK SARS-CoV-2 testing policy amongst pregnant women and babies evolved during the study. Initially, only symptomatic women and babies were tested. Routine screening of all obstetric admissions was recommended by the Royal College of Obstetricians and Gynaecologists on 29 May 2020 and neonatal testing was recommended for symptomatic babies of mothers with a SARS-CoV-2 infection; testing of asymptomatic babies varied.10 Confirmation of neonatal SARS-CoV-2 infection required at least two positive samples, including one at least 72 h after birth.10 UK policy was that well babies of SARS-CoV-2-infected mothers should be cared for alongside their mothers in the postnatal ward. This report presents the characteristics and short-term outcomes for babies born to a mother with confirmed SARS-CoV-2 infection in the 7 days before or after birth between 1 March and 31 August 2020 and for whom complete data had been received by 14 January 2021. Maternal admission criteria were based on locally defined clinical indications.11 Neonatal intensive care was defined using the British Association of Perinatal Medicine criteria.12 Denominator data for total NNU admissions over the study period were obtained from the NNRD and data describing maternal SARS-CoV-2 infections were taken from the UKOSS which recorded all pregnant women in hospitals with confirmed SARS-CoV-2 infection.11 Parent, patient and public involvement Parents, patients and the public were consulted during the design of the study and presentation of the findings through the MBRRACE-UK and the NIHR Policy Research Unit in the Maternal and Neonatal Care third-sector stakeholder groups comprising representatives from all the relevant national mother and baby charities in the UK. Statistical analysis Descriptive statistics are presented as means with standard deviations and medians with interquartile ranges. Results There were 309,518 live births during the study period; 1019 babies were born in the UK to mothers known to have SARS-CoV-2 infection within 7 days of birth during the study period (634 symptomatic mothers, 385 asymptomatic mothers). All were singleton pregnancies. Monthly BPSU card returns were received from between 87.0% and 91.3% of 4091 UK paediatricians each month; 340 potentially eligible babies were reported through the BPSU system and 177 through UKOSS surveillance (Fig. 1). After de-duplication and exclusion of ineligible babies, 111/1019 (10.9%) were admitted to an NNU following maternal SARS-CoV-2 infection around birth.Fig. 1 Flowchart of case selection for the study period 1st March 2020 to 31st August 2020. This flowchart describes how cases were selected including the linkage between BPSU data and UKOSS data. During the study period, 56,179 babies were admitted to an NNU for any reason. Therefore, overall 2 per 1000 (95% CI 1.6-2.4) neonatal admissions were of babies born to mothers with SARS-CoV-2 infection around the time of birth. The highest proportions were in March and April 2020 (3.4 and 6.7 per 1000 admissions, respectively) (Fig. 2). 74/111 babies (67%) were born preterm (<37 weeks' gestation), including 26 (23%) born very preterm (<32 weeks' gestation). Over the study period, 6 per 1000 (95% CI 4.4-9.4) very preterm neonatal admissions were babies born to mothers with perinatal SARS-CoV-2 infection. Among babies admitted for neonatal care, 55/111 babies (50%) were born to mothers from non-white ethnic groups (Table 1).Fig. 2 Proportion of babies admitted for neonatal care following maternal coronavirus. Babies admitted for neonatal care following maternal coronavirus as a proportion per 1,000 of total monthly neonatal admissions between March 2020 to 31st August 2020. Table 1 Maternal and birth characteristics for babies admitted for neonatal care following maternal SARS-CoV-2 infection around the time of birth in the UK by maternal intensive care status. Neonatal care following maternal SARS-CoV-2 around the time of birth Neonatal care following maternal intensive care Neonatal care following maternal non-intensive care Number 111 28a 76a Maternal age <35 years 62 (55%) 13 (46%) 49 (65%) >=35 years 42 (38%) 15 (54%) 27 (36%) Missing 7 (6%) 0 (0%) 0 (0%) Maternal BMI Normal 33 (30%) 6 (21%) 27 (35%) Overweight 32 (29%) 14 (50%) 18 (23%) Obese 35 (32%) 7 (25%) 28 (37%) Missing 11 (10%) 1 (3%) 3 (4%) Maternal ethnicity White 48 (43%) 11 (39%) 37 (49%) Asian 25 (23%) 5 (18%) 20 (26%) Black 25 (23%) 10 (36%) 15 (20%) Other 2 (2%) 0 (0%) 2 (3%) Mixed 3 (3%) 2 (7%) 1 (1%) Missing 8 (7%) 0 (0%) 0 (0%) Antenatal steroids given Eligible (<34 weeks) 37 18 19 Full 18 (49%) 8 (44%) 10 (53%) Partial 16 (43%) 7 (39%) 9 (47%) Not indicated 3 (8%) 3 (17%) 0 (0%) Magnesium sulfate given Eligible (<30 weeks) 11 8 3 Yes 10 (90%) 7 (88%) 3 (100%) No 1 (10%) 1 (12%) 0 (0%) Not indicated Mode of birth Unassisted vaginal birth 18 (16%) 0 (0%) 18 (24%) Instrumental vaginal birth 6 (5%) 1 (4%) 5 (7%) Caesarean birth, maternal SARS-CoV-2 33 (30%) 25 (89%) 8 (11%) Caesarean birth, unrelated to SARS-CoV-2 42 (38%) 2 (7%) 40 (53%) Missing 12 (11%) 0 (0%) 2 (3%) Gestational age at birth 22-27 weeks 2 (2%) 1 (4%) 1 (1%) 28-31 weeks 24 (22%) 11 (39%) 9 (12%) 32-36 weeks 48 (43%) 14 (50%) 33 (43%) >=37 weeks 37 (33%) 2 (7%) 33 (43%) aMaternal intensive care status was missing for 7 babies. Severity of illness from SARS-CoV-2 infection among the mothers of the 111 admitted infants varied: 28/104 (27%) mother's required intensive care, of whom four died from SARS-CoV-2; maternal intensive care data were missing for seven cases. Forty of 111 (36%) babies required neonatal intensive care; 76 (68%) were treated with some form of respiratory support of whom 30 received mechanical ventilation. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy (Table 2). Eleven (10%) babies had confirmed neonatal SARS-CoV-2. In total, babies born to mothers with SARS-CoV-2 infection around birth received 2456 days of neonatal care (median 13 days [IQR 5, 34] per baby), including 295 days of intensive care (median 0 days [IQR 0, 2] per baby). At the end of follow-up, 105 (95%) babies had been discharged home and two were still admitted to an NNU. Three babies died before discharge from the NNU; outcome data were missing for one baby. In no instance was the cause of death attributed to neonatal or maternal SARS-CoV-2 infection.Table 2 Characteristics, treatments and outcomes of babies admitted for neonatal care following maternal SARS-CoV-2 around the time of birth infection in the UK by maternal intensive care status. Neonatal care following maternal SARS-CoV-2 around the time of birth Neonatal care following maternal critical care Neonatal care following maternal non-critical Number 111 28a 76a Condition at birth 5 min Apgar <7 14 (13%) 9 (32%) 5 (7%) 10 min Apgar <7 4 (4%) 3 (11%) 1 (1%) Intubated 14 (13%) 9 (32%) 5 (7%) Chest compressions 2 (2%) 1 (4%) 1 (1%) Resuscitation drugs 2 (2%) 2 (7%) 0 (0%) Highest level of care Special care 18 (16%) 3 (11%) 14 (18%) High dependency care 53 (60%) 8 (29%) 44 (58%) Intensive care 40 (36%) 17 (61%) 18 (24%) Highest respiratory support Mechanical ventilation 30 (27%) 15 (54%) 12 (16%) Non-invasive ventilation 39 (35%) 7 (25%) 29 (38%) Supplemental oxygen 7 (6%) 1 (4%) 6 (8%) Neurological condition Seizures 3 (3%) 2 (7%) 1 (1%) Therapeutic hypothermia 4 (4%) 1 (4%) 3 (4%) Neonatal outcome Discharged home 105 (95%) 26 (93%) 73 (96%) Still admitted 2 (2%) 1 (4%) 1 (1%) Died 3 (3%) 1 (4%) 2 (3%) Missing 1 (1%) 0 (0%) 0 (0%) Breastfeeding at discharge Any 37 (33%) 7 (25%) 30 (39%) Exclusive 18 (16%) 3 (11%) 15 (20%) aMaternal intensive care status was missing for 7 babies. The large majority (25/28, 89%) of mothers requiring intensive care had a SARS-CoV-2-indicated caesarean birth, compared to 11% (8/76) for mothers not receiving intensive care. Twenty-six (93%) babies born to mothers requiring intensive care were preterm compared to 43% (33/76) of babies born to mothers who were less unwell or asymptomatic (Table 1). Seven (88%) of eligible mothers requiring intensive care were given magnesium sulfate but only 8/14 (44%) were recorded as having received a full course of antenatal steroids. Only three babies born to mothers who received intensive care were exclusively breastfed at discharge from the NNU. Apgar score was lower in babies born to mothers receiving intensive care (Table 2). A total of 61% (17/28) of babies born to mothers who received intensive care required neonatal intensive care and 54% (15/28) of these babies received mechanical ventilation. Short-term outcomes at neonatal discharge were similar between babies born to mothers who received intensive care and those who did not (Table 2). Discussion Using national population-level data collected through active surveillance, we found that babies born to a mother with confirmed SARS-CoV-2 infection around birth, made up a low proportion of total neonatal admissions during the first 'wildtype' wave of the pandemic. On average 2 per 1000 neonatal admissions in this wave of the pandemic in the UK were babies of mothers infected with perinatal SARS-CoV-2 infection;13 but there was variation throughout the year in the number of babies affected by maternal SARS-CoV-2 with a considerably higher proportion of neonatal admissions related to maternal SARS-CoV-2 in March and April 2020. This trend follows the epidemiology of community cases of SARS-CoV-2 in the UK, with cases rising in March and reaching a peak in April.14 it is not possible to determine from available data the degree to which this early increase in neonatal admissions additional may be related to additional precautions rather; however, this would be unlikely as national United Kingdom guidance from the start of the pandemic was to keep babies born to SARS-CoV-2-infected mothers with their mother when clinically possible. A total of 640 women with symptomatic SARS-CoV-2 infection gave birth during the study period; further details on maternal and perinatal care and outcomes have previously been described:11 hospitalised women with symptomatic were more likely to be admitted to intensive care but the absolute risk of poor outcomes was low. Neonatal data presented here support this that mortality in babies born to mothers with SARS-CoV-2 infection around birth was low with none of the three neonatal deaths directly attributed to SARS-CoV-2 infection in mother or baby. Despite these apparently reassuring short-term outcomes, the longer-term implications of maternal SARS-CoV-2 around the time of birth may be more concerning. The rate of very preterm birth, which is strongly associated with long-term morbidity and later mortality, was 2.6% among all mothers with known perinatal SARS-CoV-2 infection who were in hospital, which is approximately double the UK national rate.9,15 Four term babies born to mothers with perinatal SARS-CoV-2 infection received therapeutic hypothermia for hypoxic ischaemic encephalopathy; numbers were low and preclude further formal analysis. Hypoxic ischaemic encephalopathy was not significantly more common in babies born to mothers with SARS-CoV-2 infection in pregnancy in Sweden, with only 3 cases seen among 2323 babies.6 This work highlights the importance of collaborative working between teams caring for pregnant women in intensive care and the maternity team.16 The low rate of administration of a full course of antenatal steroids to mothers receiving intensive care may be explained in part by the urgency of delivery, but is nevertheless concerning. It is important that SARS-CoV-2 infection is recognised as a significant cause of maternal intensive care admission, particularly in unvaccinated mothers, and appropriate measures are put in place to optimise maternal and neonatal outcomes.1 The low rates of exclusive breastfeeding at neonatal discharge in mothers receiving intensive care are likely related to multiple factors including maternal ill-health and underline the need to follow national guidance to support breastfeeding and expression of breastmilk among mothers who are receiving intensive care.17 The well-established benefits of breastfeeding, including potential transfer of passive immunity against SARS-CoV-2 to the neonate, comprehensively outweigh any unproven risk of viral transmission.18 In keeping with studies in other age groups and populations in the first pandemic wave,3 babies born to mothers from black, Asian, and mixed or other ethnic groups were over-represented in this cohort.19 This has been attributed to socioeconomic differences and compounded by the impact of systemic structural and social inequity.20,21 The major strength of this study is that it reports UK-wide, population-level data from a national health service collected through an established active surveillance system with high reporting levels, linkage with national obstetric active surveillance to ensure high case ascertainment and the addition of routinely recorded neonatal data held in the NNRD. A weakness of the study is that the true incidence of SARS-CoV-2 infection within 7 days of birth is not known because national testing of all obstetric admissions was only introduced part way through this study in May 2020. Other limitations include the absence of both longitudinal data on laboratory test results and results of neonatal imaging which may inform prognosis. Neither do we have outcomes for babies not admitted to an NNU. The long-term effects of early life exposure to SARS-CoV-2 are unknown, and ongoing data collection, linkage and follow-up are crucial. Conclusions Extremely preterm birth was more common among mothers with SARS-CoV-2 infection around the time of birth, but babies born to mothers with perinatal SARS-CoV-2 infection made up a low proportion of UK NNU admissions over the first 6 months of the UK pandemic and neonatal SARS-CoV-2 infection was uncommon in these babies. Supplementary information Supplemental material Supplementary information The online version contains supplementary material available at 10.1038/s41390-023-02527-z. Acknowledgements This research is funded by the UK NIHR Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care (PR-PRU-1217-21202). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We acknowledge the assistance of Jacob Avis and Richard Lynn at the BPSU, the BPSU reporting clinicians, the NIHR Clinical Research Networks, and other people without whose support this research would not have been possible in such a timely manner. Author contributions S.A. wrote the first draft of the article. S.A., M.A.Q., C.G., J.J.K. and A.P. carried out the analyses. All authors edited and approved the final version of the article. C.G., M.K., S.N.L., E.S.D., D.S., C.D., H.M. and J.J.K. contributed to the development and conduct of the study. C.G. as guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. C.G., M.A.Q. and J.J.K. have accessed and verified the data underlying the study. Funding The BPSU COVID-19 study is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217-21202. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The UKOSS study was funded by the National Institute for Health Research HS&DR Programme (project number 11/46/12). M.K. is an NIHR Senior Investigator. The Maternal, Newborn and Infant Clinical Outcome Review Programme, delivered by MBRRACE-UK, is commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the National Clinical Audit and Patient Outcomes Programme (NCAPOP). The Maternal, Newborn and Infant Clinical Outcome Review Programme is funded by NHS England, NHS Wales, the Health and Social Care division of the Scottish government, The Northern Ireland Department of Health, and the States of Jersey, Guernsey, and the Isle of Man. The study funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Data availability The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request. Competing interests M.L., M.A.Q. and J.J.K. received grants from the UK NIHR Policy Research Programme in relation to the submitted work. S.A., A.M., M.H., A.P., S.N.L., E.S.D., D.S., C.D., H.M. and C.G. declare no competing interests. Ethics approval and consent to participate The study was approved by the North East - Newcastle & North Tyneside 2 Research Ethics Committee (IRAS ID 282127; REC 20/NE/0107). Data were collected in England and Wales without parental consent following Section 251 advice from the Confidentiality Advisory Group of the Health Research Authority (20/CAG/0058) and under the COVID-19 notice issued by the Secretary of State for Health and Social Care under Regulation 3(4) of the Health Service Control of Patient Information Regulations 2002. Data were collected in Scotland without parental consent following COVID-19 rapid review and advice from the Public Benefit and Privacy Panel for Health and Social Care (PBPP) (1920-0288) and with maternal consent following advice from the Privacy Commissioner in Northern Ireland. All NNUs agreed to the inclusion of their NNRD data in the study. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. These authors contributed equally: Maria A. Quigley, Chris Gale. References 1. Vousden N Severity of maternal infection and perinatal outcomes during periods of SARS-CoV-2 wildtype, alpha, and delta variant dominance in the UK: prospective cohort study BMJ Med. 2022 1 e000053 10.1136/bmjmed-2021-000053 36936566 2. Gale C National active surveillance to understand and inform neonatal care in COVID-19 Arch. Dis. Child Fetal Neonatal Ed. 2020 105 346 347 10.1136/archdischild-2020-319372 32536607 3. Swann OV Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study BMJ 2020 370 m3249 10.1136/bmj.m3249 32960186 4. 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