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Carbon monoxide exposure of subjects with documented cardiac arrhythmias
Chaitman, B.R.; Dahms, T.E.; Byers, S.; Carroll, L.W.; Younis, L.T.; Wiens, R.D. )
The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity.
Cardiac arrhythmias in pregnancy.
Knotts, Robert J; Garan, Hasan
As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias. PMID:25037518
Ranolazine in Cardiac Arrhythmia.
Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C
Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200
Mechanisms of cardiac arrhythmias
Tse, Gary
Blood circulation is the result of the beating of the heart, which provides the mechanical force to pump oxygenated blood to, and deoxygenated blood away from, the peripheral tissues. This depends critically on the preceding electrical activation. Disruptions in the orderly pattern of this propagating cardiac excitation wave can lead to arrhythmias. Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cardiac action potential, which is discussed in the first part of this review. A brief outline of the different classification systems for arrhythmogenesis is then provided, followed by a detailed discussion for each mechanism in turn, highlighting recent advances in this area. PMID:27092186
Carbon monoxide exposure of subjects with documented cardiac arrhythmias. Research report, August 1987-July 1991
Chaitman, B.R.; Dahms, T.E.; Byers, S.; Carroll, L.W.; Younis, L.T.
The authors studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. Subjects were selected and enrolled in a randomized double-blind study; the carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. Total and repetitive ventricular arrhythmias were measured for four specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide exposure; (3) six hours after carbon monoxide exposure; and (4) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 + or - 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 + or - 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 + or - 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. However, patients with symptomatic ventricular arrhythmias and symptomatic myocardial ischemia were excluded from the present study.
Lysophosphatidylcholine (LPC) metabolism and cardiac arrhythmias
Giffin, D.M.; Man, R.Y.K.; Arthur, G.; Choy, P.C.
The effect of LPC in the production of cardiac arrhythmias in isolated mammalian hearts has been well-documented. Cardiac arrhythmias are initiated by the accumulation of the lysolipid in the cardiac membrane. When isolated rat hearts were perfused in 10 ..mu..M LPC for 10 min, severe arrhythmias were observed in all experiments. In isolated guinea pig hearts that were perfused under identical conditions, the development of severe arrhythmias was never observed, and mild arrhythmias were produced in less than 50% of the hearts used. When the hearts of both species were perfused with (/sup 14/C-palmitate)-LPC, the labellings found in the microsomal fractions (expressed in mg protein) were similar. However, a higher amount of labelled LPC (2-fold) was found in rat heart microsomes, whereas a higher amount of labelled fatty acid was located in the guinea pig heart microsomes. Determination of lysophospholipase activities in these microsomal fractions revealed that the specific activity of the enzyme was much higher in the guinea pig heart than the rat heart. The authors conclude that the differential effect of LPC-induced arrhythmias between the rat and guinea pig heart may be a direct result of the lysophospholipase activities in these hearts. The ability to catabolize LPC more rapidly in the guinea pig heart may decrease the accumulation of LPC in the membrane, and hence, reduce the production of arrhythmias.
Inherited arrhythmias: The cardiac channelopathies.
Behere, Shashank P; Weindling, Steven N
Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms "Long QT Syndrome" (MeSH) and "Short QT Syndrome" (MeSH) and "Brugada Syndrome" (MeSH) and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID:26556967
Inherited arrhythmias: The cardiac channelopathies
Behere, Shashank P; Weindling, Steven N
Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms "Long QT Syndrome" (MeSH) and "Short QT Syndrome" (MeSH) and "Brugada Syndrome" (MeSH) and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID:26556967
Microwave Treatment for Cardiac Arrhythmias
NASA Technical Reports Server (NTRS)
Arndt, G. Dickey (Inventor); Carl, James R. (Inventor); Raffoul, George W. (Inventor); Pacifico, Antonio (Inventor)
Method and apparatus are provided for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue to treat ventricular tachycardia and other arrhythmias while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In operation, microwave energy between about 1 Gigahertz and 12 Gigahertz is applied to monopole microwave radiator having a surface wave limiter. A test setup provides physical testing of microwave radiators to determine the temperature profile created in actual heart tissue or ersatz heart tissue. Saline solution pumped over the heart tissue with a peristaltic pump simulates blood flow. Optical temperature sensors disposed at various tissue depths within the heart tissue detect the temperature profile without creating any electromagnetic interference. The method may be used to produce a desired temperature profile in other body tissues reachable by catheter such as tumors and the like.
Cardiac arrhythmias during or after epileptic seizures
van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D
Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: 'cardiac arrhythmias' and 'epilepsy'. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP. PMID:26038597
Cardiac Arrhythmias In Congenital Heart Diseases
Khairy, Paul; Balaji, Seshadri
Arrhythmias figure prominently among the complications encountered in the varied and diverse population of patients with congenital heart disease, and are the leading cause of morbidity and mortality. The incidence generally increases as the patient ages, with multifactorial predisposing features that may include congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical or hypoxic stress, and residual or postoperative sequelae. The safe and effective management of arrhythmias in congenital heart disease requires a thorough appreciation for conduction system variants, arrhythmia mechanisms, underlying anatomy, and associated physiology. We, therefore, begin this review by presenting the scope of the problem, outlining therapeutic options, and summarizing congenital heart disease-related conduction system anomalies associated with disorders of the sinus node and AV conduction system. Arrhythmias encountered in common forms of congenital heart disease are subsequently discussed. In so doing, we touch upon issues related to risk stratification for sudden death, implantable cardiac devices, catheter ablation, and adjuvant surgical therapy. PMID:19898654
Cardiac arrhythmias associated with spinal cord injury
Hector, Sven Magnus; Biering-Sørensen, Tor; Krassioukov, Andrei; Biering-Sørensen, Fin
Context/Objectives To review the current literature to reveal the incidence of cardiac arrhythmias and its relation to spinal cord injury (SCI). Methods Data source: MEDLINE database, 304 hits, and 32 articles were found to be relevant. The relevant articles all met the inclusion criteria: (1) contained original data (2) on cardiac arrhythmias (3) in humans with (4) traumatic SCI. Results In the acute phase of SCI (1–14 days after injury) more cranial as well as more severe injuries seemed to increase the incidence of bradycardia. Articles not covering the first 14 days after injury, thus describing the chronic phase of SCI, showed that individuals with SCI did not have a higher incidence of cardiac arrhythmias compared with able-bodied controls. Furthermore, their heart rate did not differ significantly. Penile vibro-stimulation was the procedure investigated most likely to cause bradycardia, which in turn was associated with episodes of autonomic dysreflexia. The incidence of bradycardia was found to be 17–77% for individuals with cervical SCI. For individuals with thoracolumbar SCI, the incidence was 0–13%. Conclusion Bradycardia was commonly seen in the acute stage after SCI as well as during procedures such as penile vibro-stimulation and tracheal suction. These episodes of bradycardia were seen more often in individuals with cervical injuries. Longitudinal studies with continuous electrocardiogram recordings are needed to uncover the true relation between cardiac arrhythmias and SCI. PMID:24090076
Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.
Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth
Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke. PMID:26802767
Non-invasive Mapping of Cardiac Arrhythmias.
Shah, Ashok; Hocini, Meleze; Haissaguerre, Michel; Jaïs, Pierre
Since more than 100 years, 12-lead electrocardiography (ECG) is the standard-of-care tool, which involves measuring electrical potentials from limited sites on the body surface to diagnose cardiac disorder, its possible mechanism, and the likely site of origin. Several decades of research has led to the development of a 252-lead ECG and computed tomography (CT) scan-based three-dimensional electro-imaging modality to non-invasively map abnormal cardiac rhythms including fibrillation. These maps provide guidance towards ablative therapy and thereby help advance the management of complex heart rhythm disorders. Here, we describe the clinical experience obtained using non-invasive technique in mapping the electrical disorder and guide the catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats), and ventricular pre-excitation (Wolff-Parkinson-White syndrome). PMID:26072438
Microwave Treatment for Cardiac Arrhythmias
NASA Technical Reports Server (NTRS)
Hernandez-Moya, Sonia
NASA seeks to transfer the NASA developed microwave ablation technology, designed for the treatment of ventricular tachycardia (irregular heart beat), to industry. After a heart attack, many cells surrounding the resulting scar continue to live but are abnormal electrically; they may conduct impulses unusually slowly or fire when they would typically be silent. These diseased areas might disturb smooth signaling by forming a reentrant circuit in the muscle. The objective of microwave ablation is to heat and kill these diseased cells to restore appropriate electrical activity in the heart. This technology is a method and apparatus that provides for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In comparison with other methods that involve direct-current pulses or radio frequencies below 1 GHz, this method may prove more effective in treating ventricular tachycardia. This is because the present method provides for greater control of the location, cross-sectional area, and depth of a lesion via selection of the location and design of the antenna and the choice of microwave power and frequency.
Classification of cardiac arrhythmias using competitive networks.
Leite, Cicilia R M; Martin, Daniel L; Sizilio, Glaucia R A; Dos Santos, Keylly E A; de Araujo, Bruno G; Valentim, Ricardo A M; Neto, Adriao D D; de Melo, Jorge D; Guerreiro, Ana M G
Information generated by sensors that collect a patient's vital signals are continuous and unlimited data sequences. Traditionally, this information requires special equipment and programs to monitor them. These programs process and react to the continuous entry of data from different origins. Thus, the purpose of this study is to analyze the data produced by these biomedical devices, in this case the electrocardiogram (ECG). Processing uses a neural classifier, Kohonen competitive neural networks, detecting if the ECG shows any cardiac arrhythmia. In fact, it is possible to classify an ECG signal and thereby detect if it is exhibiting or not any alteration, according to normality. PMID:21096338
HERG1 Channel Agonists and Cardiac Arrhythmia
Sanguinetti, Michael
Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650
HERG1 channel agonists and cardiac arrhythmia.
Sanguinetti, Michael C
Type 1 human ether-a-go-go-related gene (hERG1) potassium channels are a key determinant of normal repolarization of cardiac action potentials. Loss of function mutations in hERG1 channels cause inherited long QT syndrome and increased risk of cardiac arrhythmia and sudden death. Many common medications that block hERG1 channels as an unintended side effect also increase arrhythmic risk. Routine preclinical screening for hERG1 block led to the discovery of agonists that shorten action potential duration and QT interval. Agonists have the potential to be used as pharmacotherapy for long QT syndrome, but can also be proarrhythmic. Recent studies have elucidated multiple mechanisms of action for these compounds and the structural basis for their binding to the pore domain of the hERG1 channel. PMID:24721650
Basic Cardiac Electrophysiology and Common Drug-induced Arrhythmias.
Lee, Aimee; Pickham, David
Drugs can be a double-edged sword, providing the benefit of symptom alleviation and disease modification but potentially causing harm from adverse cardiac arrhythmic events. Proarrhythmia is the ability of a drug to cause an arrhythmia, the number one reason for drugs to be withdrawn from the patient. Drug-induced arrhythmias are defined as the production of de novo arrhythmias or aggravation of existing arrhythmias, as a result of previous or concomitant pharmacologic treatment. This review summarizes normal cardiac cell and tissue functioning and provides an overview of drugs that effect cardiac repolarization and the adverse effects of commonly administered antiarrhythmics. PMID:27484663
Method for classifying cardiac arrhythmias using photoplethysmography.
Polania, Luisa F; Mestha, Lalit K; Huang, David T; Couderc, Jean-Philippe
Advances in mobile computing and miniature devices have contributed to the accelerated development of wearable technologies for clinical applications. The new trend of wearable technologies has fostered a growth of interest for sensors that can be easily integrated into wearable devices. In particular, photoplethysmography (PPG) is especially suitable for wearable sensing, as it is low-cost, noninvasive, and does not require wet electrodes like the electrocardiogram. Photoplethysmograph signals contain rich information about the blood pulsating variation which is strongly related to the electrical activities of the heart. Therefore, in this paper we hypothesize that the ambulatory PPG monitoring could be employed for arrhythmia detection and classification. This paper presents a method for classifying ventricular premature contraction (VPC) and ventricular tachycardia (VT) from normal sinus rhythm (NSR) and supraventricular premature contraction (SVPC) recorded in patients going through ablation therapy for arrhythmia. Although occasional VPCs are benign, the increase in the frequency of VPC events may lead to VT, which in turn,could evolve into ventricular fibrillation and sudden cardiac death. Therefore the accurate measurement of VPC frequency and early detection of VT events becomes essential for patients with cardiac disease. PMID:26737799
Fetal Arrhythmias Associated with Cardiac Rhabdomyomas
Wacker-Gussmann, Annette; Strasburger, Janette F; Cuneo, Bettina; Wiggins, Delonia; Gotteiner, Nina; Wakai, Ronald T
Background Primary heart tumors in fetuses are rare and mainly represent rhabdomyomas. The tumors have a variable expression and can be associated with arrhythmias, including both wide and narrow QRS tachycardia. Although multiple Doppler techniques exist to assess fetal heart rhythm, it can be difficult to record precise electrophysiological pathologies in fetal life. Objective Investigations defining precise electrophysiological diagnosis were performed using fetal magnetocardiography (fMCG). Methods In addition to routine fetal echocardiography, fMCG was used to investigate electrophysiologic rhythm patterns in a series of 10 fetuses with cardiac rhabdomyomas. Results The mean gestational age of the fetuses was 28.6 weeks (SD ± 4.7 weeks). The multiple rhabdomyomas were mainly located in the right and left ventricles as well as around the AV groove. Arrhythmias or conduction abnormalities were diagnosed in all 10 patients, although only six of them were referred due to that indication. Remarkably, 80% (8/10) had associated Wolff-Parkinson-White pre-excitation. In addition, we found prominent p waves in four fetuses. Conclusion In fetuses with rhabdomyomas, a disease where rhythm pathology is common, precise electrophysiological diagnosis can now be made by fMCG. fMCG is complimentary to echocardiography for rhythm assessment, and can detect conduction abnormalities that are not possible to diagnose prenatally with M-mode or pulsed Doppler ultrasound. Risk factor assessment using fMCG can support pregnancy management and post-natal treatment and follow-up. PMID:24333285
Ethanol for the treatment of cardiac arrhythmias
Schurmann, Paul; Peñalver, Jorge; Valderrábano, Miguel
Introduction Ethanol infusion was an early mode of ablative treatment for cardiac arrhythmias. Its initial descriptions involved coronary intra-arterial delivery, targeting arrhythmogenic substrates in drug-refractory ventricular tachycardia or the atrioventricular node. Largely superseded by radiofrequency ablation (RFA) and other contact-based technologies as a routine ablation strategy, intracoronary arterial ethanol infusion remains as an alternative option in the treatment of ventricular tachycardia when conventional ablation fails. Arrhythmic foci that are deep-seated in the myocardium may not be amenable to catheter ablation from either the endocardium or the epicardium by RFA, but they can be targeted by an ethanol infusion. Recent findings Recently, we have explored ethanol injection through cardiac venous systems, in order to avoid the risks of complications and limitations of coronary arterial instrumentation. Vein of Marshall ethanol infusion is being studied as an adjunctive procedure in ablation of atrial fibrillation, and coronary venous ethanol infusion for ventricular tachycardia. Conclusion Ethanol ablation remains useful as a bail-out technique for refractory cases to RFA, or as an adjunctive therapy that may improve the efficacy of catheter ablation procedures. PMID:26049378
Cardiac Arrhythmia Management: Why Women Are Different from Men
... led to incorrect diagnoses including anxiety neurosis and panic attacks. However, since serotonin reuptake inhibitors can be effective ... Cardiac Arrhythmia Management in Women | Heart Disease Facts | Panic Attack or Heart Attack | Three Women from New Jersey | ...
Maternal cardiac arrhythmias during pregnancy and lactation
Cordina, Rachael; McGuire, Mark A
Arrhythmias occurring during pregnancy can cause significant symptoms and even death in mother and fetus. The management of these arrhythmias is complicated by the need to avoid harm to the fetus and neonate. It is useful to classify patients with arrhythmias into those with and without structural heart disease. Those with a primary electrical problem, but an otherwise normal heart, often tolerate rapid heart rates without compromise whereas patients with problems such as rheumatic heart disease, congenital heart disease or cardiomyopathy may quickly decompensate during an arrhythmia.
[Cardiac arrhythmias in targeted connexin deficient mice: significance for the arrhythmia field].
Hagendorff, A; Plum, A
Intercellular communication can be mediated by gap junction channels. One channel is composed of two hexameric hemichannels which consist of six polypeptide subunits called connexines (Cx). Three different connexines were documented in the cardiac myocytes: Cx40, Cx43 and Cx45. The labeling by number represents the rounded, molecular mass of the amino acid sequences given in kD. Identical connexons form homotypic channels different connexons can form heterotypic channels. Each channel type has specific properties regarding permeability and electrical conductance. Beside a typical age-dependent alignment of gap junction channels on the surface of the cardiac myocytes, regional distribution of the different connexins is different at distinct parts of the mouse heart. The ventricular working myocardium is characterized by Cx43, whereas Cx40 and Cx45 were not found in this region. In the atria as well as in the conduction system, Cx40 is the most frequently expressed. Cx45 appears to form a border zone between conductive and the surrounding working myocardium. In line with the localization and the conduction properties of distinct homotypic gap junction channels, the Cx43 deficient mouse is suitable for analysis of ventricular arrhythmias and the Cx40 deficient mouse primarily for studies of atrial arrhythmias. Increased ventricular conduction velocity and increased ventricular vulnerability were observed in the presence of a decreased number and density of Cx43 gap junction channels. This observation, however, is controversially discussed. Cx40 deficiency induces an impairment of the sinuatrial, intraatrial and atrioventricular conduction properties and is associated with an increased atrial vulnerability. Transgenic mouse models and new mapping techniques for detection of the electrical wavefront propagation provide new insights into the mechanisms of arrhythmogenesis. Geneticists, clinicians and basic researchers need to collaborate in order to explore the clinical
Misaki, Takuro; Fukahara, Kazuaki
The success of the radiofrequency catheter ablation procedure for most types of supraventricular and ventricular tachycardia largely eliminated the role of surgical therapy of arrhythmias. However, there remains a subset of arrhythmia patients in whom urgent surgical treatments are required. In this review we mention recent developments of the urgent surgical treatment for arrhythmias. In cases with complete atrioventricular (AV) block and ventricular fibrillation which associated with sudden death, temporary cardiac pacing and cardiac defibrillation using direct current (DC) cardioversion must be immediately induced and followed by implantation of permanent cardiac pacemaker or implantable cardioverter defibrillator (ICD), if necessary. In addition to usual cardiac pacing therapy, novel pacing therapy has been developed recently for the patients with symptomatic heart failure. Cardiac resynchronization therapy (CRT) using biventricular pacing is an emerging therapy for improvement of cardiac function in patients with heart failure in association with intraventricular conduction delay. To prevent the sudden death in patients with heart failure, biventricular pacing combined with ICD are also implanted and its efficacy are reported. With the exception of the pacing therapy, curative surgical treatments are limited in drug-refractory atrial fibrillation and ventricular fibrillation/tachycardia after myocardial infarction requiring Dor's type operation. In any case surgical treatment must be performed promptly and suitably with lower invasive methods. PMID:15362552
Cardiac arrhythmias during exercise testing in healthy men.
NASA Technical Reports Server (NTRS)
Beard, E. F.; Owen, C. A.
Clinically healthy male executives who participate in a long-term physical conditioning program have demonstrated cardiac arrhythmia during and after periodic ergometric testing at submaximal and maximal levels. In 1,385 tests on 248 subjects, it was found that 34% of subjects demonstrated an arrhythmia at some time and 13% of subjects developed arrhythmia on more than one test. Premature systoles of ventricular origin were most common, but premature systoles of atrial origin, premature systoles of junctional origin, paroxysmal atrial tachycardia, atrioventricular block, wandering pacemaker, and pre-excitation were also seen. Careful post-test monitoring and pulse rate regulated training sessions are suggested for such programs.
Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?
Stunnenberg, Bas C; Deinum, Jaap; Links, Thera P; Wilde, Arthur A; Franssen, Hessel; Drost, Gea
It is unknown how often cardiac arrhythmias occur in hypokalemic periodic paralysis (HypoPP) and if they are caused by hypokalemia alone or other factors. This systematic review shows that cardiac arrhythmias were reported in 27 HypoPP patients. Cases were confirmed genetically (13 with an R528H mutation in CACNA1S, 1 an R669H mutation in SCN4A) or had a convincing clinical diagnosis of HypoPP (13 genetically undetermined) if reported prior to the availability of genetic testing. Arrhythmias occurred during severe hypokalemia (11 patients), between attacks at normokalemia (4 patients), were treatment-dependent (2 patients), or unspecified (10 patients). Nine patients died from arrhythmia. Convincing evidence for a pro-arrhythmogenic factor other than hypokalemia is still lacking. The role of cardiac expression of defective skeletal muscle channels in the heart of HypoPP patients remains unclear. Clinicians should be aware of and prevent treatment-induced cardiac arrhythmia in HypoPP. PMID:25088161
Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia
Watts, Simon J.; Hunter, Amanda J.; Shah, Anoop S.V.; Bosson, Jenny A.; Unosson, Jon; Barath, Stefan; Lundbäck, Magnus; Cassee, Flemming R.; Donaldson, Ken; Sandström, Thomas; Blomberg, Anders; Newby, David E.; Mills, Nicholas L.
Background: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups. Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease. Methods: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population. Results: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease. Conclusions: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions. Citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundbäck M, Cassee FR, Donaldson K, Sandström T, Blomberg A, Newby DE, Mills NL. 2014. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect 122:747–753; http://dx.doi.org/10.1289/ehp.1307337 PMID:24667535
Cardiac arrhythmias in space. Role of vagotonia.
Leguay, G; Seigneuric, A
Rhythm disorders observed in space have always been minor but they are not unfrequent. They include: ventricular or supra-ventricular extrasystoles, nodal arrhythmias, auriculo-ventricular conduction disorders. There are several etiopathogenetic hypotheses: a strict selection must permit its elimination of an underlying heart disease; the potassium deficiency is often advanced but its role is not certain; the role of catecholamines is also discussed; the role of hypervagotony is extensively analysed as great clinical and electro-cardiographic evidence speaks for it. It can induce disorders which are more serious than those observed so far, particularly fibrillation or intermittent atrial flutter; weightlessness itself could partly condition the vagotonic state; and the effects of fluid shifts are also discussed from this point of view. The possible therapies for various atrial, nodal, ventricular disorders are reviewed, with greater detail for vagal atrial arrhythmias. PMID:11542963
Circadian rhythms in cardiac arrhythmias and opportunities for their chronotherapy.
Portaluppi, Francesco; Hermida, Ramón C
It is now well established that nearly all functions of the body, including those that influence the pharmacokinetics and pharmacodynamics of medications, exhibit significant 24-hour variation. The electrical properties of the heart as well as cardiac arrhythmias also vary as circadian rhythms, even though the suboptimal methods initially used for their investigation slowed their identification and thorough characterization. The application of continuous Holter monitoring of the electrical properties of the heart has revealed 24-hour variation in the occurrence of ventricular premature beats with the peak in events, in diurnally active persons, between 6 a.m. and noon. After the introduction of implantable cardioverter-defibrillators, ventricular tachycardia or fibrillation were also found to peak in the same period of the day. Even defibrillator energy requirements show circadian variation, thus supporting the need for a temporal awareness in the therapeutic approach to arrhythmias. Imbalanced autonomic tone, circulating levels of catecholamines, increased heart rate and blood pressure, all established determinants of cardiac arrhythmias, show circadian variations and underlie the genesis of the circadian pattern of cardiac arrhythmias. Arrhythmogenesis appears to be suppressed during nighttime sleep, and this can influence the evaluation of the efficacy of antiarrhythmic medications in relation to their administration time. Unfortunately, very few studies have been undertaken to assess the proper timing (chronotherapy) of antiarrhythmic medications as means to maximize efficacy and possibly reduce side effects. Further research in this field is warranted and could bring new insight and clinical advantage. PMID:17659808
Innovation in the diagnosis and treatment of cardiac arrhythmias.
Friedman, Paul A; Eldar, Michal; Ovsyshcher, I Eli
The 11th International Dead Sea Symposium on Cardiac Arrhythmias and Device Therapy - the 20th Anniversary of the meeting - was held in Jerusalem, Israel on the 26-29 February 2012. The global meeting was conducted with the goal of providing a venue for a multidisciplinary approach to exchange knowledge in all areas related to arrhythmia care. In addition to presentations of original research and keynote lectures, special educational sessions were offered that included hands-on anatomy training and interesting case presentations. A series of innovations sessions included presentations by start-up companies and inventors, leveraging the venue's entrepreneurial environment. PMID:23030286
Caveolae, Ion Channels and Cardiac Arrhythmias
Balijepalli, Ravi C.; Kamp, Timothy J.
Caveolae are specialized membrane microdomains enriched in cholesterol and sphingolipids which are present in multiple cell types including cardiomyocytes. Along with the essential scaffolding protein caveolin-3, a number of different ion channels and transporters have been localized to caveolae in the heart including L-type Ca2+ channels (Cav1.2), Na+ channels (Nav1.5), pacemaker channels (HCN4), Na+/Ca2+ exchnager (NCX1) and others. Closely associated with these channels are specific macromolecular signaling complexes that provide highly localized regulation of the channels. Mutations in the caveolin-3 gene (CAV3) have been linked with the congenital long QT syndrome (LQT9), and mutations in caveolar-localized ion channels may contribute to other inherited arrhythmias. Changes in the caveolar microdomain in acquired heart disease may also lead to dysregulation and dysfunction of ion channels, altering the risk of arrhythmias in conditions such as heart failure. This review highlights the existing evidence identifying and characterizing ion channels localized to caveolae in cardiomyocytes and their role in arrhythmogenesis. PMID:19351512
Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.
Goudis, Christos A; Konstantinidis, Athanasios K; Ntalas, Ioannis V; Korantzopoulos, Panagiotis
Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed. PMID:26218181
Macrolide Antibiotics and the Risk of Cardiac Arrhythmias
Schuller, Joseph L.
Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non–cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended. PMID:24707986
Development of a remote handheld cardiac arrhythmia monitor.
Singh, Swaroop S; Hsiao, Henry S
In this paper we present the design and development of a real-time remote handheld cardiac arrhythmic monitoring system (RCAM). A client-server model based on Internet protocols was used. ECG data was transmitted from the remote handheld client to a centralized server, where the QRS and premature ventricular contraction detection algorithms were implemented and graded depending on the number and pattern of PVCs present. The QRS sensitivity and specificity on ECG records from Physionet archives in absence of arrhythmia was 100% and 99.62%, while in presence of arrhythmia was 99.34% and 99.31%. The average 'negative time' measured on ventricular tachyarrhythmia records was 92 seconds. The RCAM can provide remote detection of cardiac abnormalities and give specific diagnosis and recommendations of actions to be taken immediately. The limitation due to the inability of the PDA to perform complex computations was overcome by the use of the remote server. PMID:17947043
Update on management of cardiac arrhythmias in acute coronary syndromes.
Willich, T; Goette, A
This review summarizes different types of arrhythmias in patients with acute coronary syndromes and provides an overview of the available therapeutic options for acute care and management of critical arrhythmias. The different therapeutic options are depending on the origin and type of arrhythmia. The main common dominant mechanisms are intramural re-entry in ischemia and triggered activity in reperfusion. The different forms of arrhythmia were explained in detail. Atrial arrhythmias are mainly atrial fibrillation; other forms are rare and usually self-limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias can be divided in premature ventricular complexes, accelerated idioventricular rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are available. The treatment with antiarrhythmic drug is rather cautious recommended, with the exception of beta-blockers. An additional drug therapy with ranolazine may be considered. The advantage of ICD therapy for long-term primary or secondary prophylactic therapy has been well documented. ICD therapy is associated with significant reduction in mortality compared with antiarrhythmic drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and stellate ganglion blockade are rather intended as therapeutically options for incessant VT/VF or electrical storm. PMID:25612305
Nonlinear dynamics, chaos and complex cardiac arrhythmias
NASA Technical Reports Server (NTRS)
Glass, L.; Courtemanche, M.; Shrier, A.; Goldberger, A. L.
Periodic stimulation of a nonlinear cardiac oscillator in vitro gives rise to complex dynamics that is well described by one-dimensional finite difference equations. As stimulation parameters are varied, a large number of different phase-locked and chaotic rhythms is observed. Similar rhythms can be observed in the intact human heart when there is interaction between two pacemaker sites. Simplified models are analyzed, which show some correspondence to clinical observations.
Feature-based MRI data fusion for cardiac arrhythmia studies.
Magtibay, Karl; Beheshti, Mohammadali; Foomany, Farbod Hosseyndoust; Massé, Stéphane; Lai, Patrick F H; Zamiri, Nima; Asta, John; Nanthakumar, Kumaraswamy; Jaffray, David; Krishnan, Sridhar; Umapathy, Karthikeyan
Current practices in studying cardiac arrhythmias primarily use electrical or optical surface recordings of a heart, spatially limited transmural recordings, and mathematical models. However, given that such arrhythmias occur on a 3D myocardial tissue, information obtained from such practices lack in dimension, completeness, and are sometimes prone to oversimplification. The combination of complementary Magnetic-Resonance Imaging (MRI)-based techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) could provide more depth to current practices in assessing the cardiac arrhythmia dynamics in entire cross sections of myocardium. In this work, we present an approach utilizing feature-based data fusion methods to demonstrate that complimentary information obtained from electrical current distribution and structural properties within a heart could be quantified and enhanced. Twelve (12) pairs of CDI and DTI image data sets were gathered from porcine hearts perfused through a Langendorff setup. Images were fused together using feature-based data fusion techniques such as Joint Independent Component Analysis (jICA), Canonical Correlation Analysis (CCA), and their combination (CCA+jICA). The results suggest that the complimentary information of cardiac states from CDI and DTI are enhanced and are better classified with the use of data fusion methods. For each data set, an increase in mean correlations of fused images were observed with 38% increase from CCA+jICA compared to the original images while mean mutual information of the fused images from jICA and CCA+jICA increased by approximately three-fold. We conclude that MRI-based techniques present potential viable tools in furthering studies for cardiac arrhythmias especially Ventricular Fibrillation. PMID:26970857
The EINTHOVEN system: toward an improved cardiac arrhythmia monitor.
Widman, L. E.
Contemporary cardiac arrhythmia monitors, used commonly in intensive care settings, are highly sensitive to artifact, resulting in high false alarm rates, inability to detect P waves reliably, and crude rhythm interpretation. We report on two new approaches that address these problems: a noise preprocessor that characterizes the type and degree of artifact in an ECG, and a model-based rhythm interpretation algorithm. PMID:1807639
Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.
Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios
Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies. PMID:22809542
Statistical Versus Individual Forecasting Of Life-Threatening Cardiac Arrhythmias
NASA Astrophysics Data System (ADS)
Wessel, Niels; Meyerfeldt, Udo; Ziehmann, Christine; Schirdewan, Alexander; Kurths, Jürgen
Ventricular tachycardia or fibrillation (VT) as fatal cardiac arrhythmias are the main factors triggering sudden cardiac death. The objective of this investigation is to find early signs of sustained VT in patients with an implanted cardioverter-defibrillator (ICD). These devices are able to safeguard patients by returning their hearts to a normal rhythm via strong defibrillatory shocks; additionally, they are able to store at least 1000 beat-to-beat intervals immediately before the onset of a life-threatening arrhythmia. We study these 1000 beat-to-beat intervals of 63 chronic heart failure ICD patients before the onset of a life-threatening arrhythmia and at a control time, i.e. without VT event. To characterize these rather short data sets, we calculate heart rate variability (HRV) parameters from time and frequency domain, from symbolic dynamics as well as the finite-time growth rates. We find that no linear parameter shows significant differences in HRV between the VT and the control time series. However, the nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (p<0.05, for time series with less than 10% ectopy). Finally, we are investigating whether these results may lead to individual predictions of VT.
Multiple cardiac arrhythmia recognition using adaptive wavelet network.
Lin, Chia-Hung; Chen, Pei-Jarn; Chen, Yung-Fu; Lee, You-Yun; Chen, Tainsong
This paper proposes a method for electrocardiogram (ECG) heartbeat pattern recognition using adaptive wavelet network (AWN). The ECG beat recognition can be divided into a sequence of stages, starting from feature extraction and conversion of QRS complexes, and then identifying cardiac arrhythmias based on the detected features. The discrimination method of ECG beats is a two-subnetwork architecture, consisting of a wavelet layer and a probabilistic neural network (PNN). Morlet wavelets are used to extract the features from each heartbeat, and then PNN is used to analyze the meaningful features and perform discrimination tasks. The AWN is suitable for application in a dynamic environment, with add-in and delete-off features using automatic target adjustment and parameter tuning. The experimental results obtained by testing the data of the MIT-BIH arrhythmia database demonstrate the efficiency of the proposed method. PMID:17281539
Classification enhancible grey relational analysis for cardiac arrhythmias discrimination.
Lin, Chia-Hung
This paper proposes a method for electrocardiogram (ECG) heartbeat recognition using classification enhancible grey relational analysis (GRA). The ECG beat recognition can be divided into a sequence of stages, starting with feature extraction and then according to characteristics to identify the cardiac arrhythmias including the supraventricular ectopic beat, bundle branch ectopic beat, and ventricular ectopic beat. Gaussian wavelets are used to enhance the features from each heartbeat, and GRA performs the recognition tasks. With the MIT-BIH arrhythmia database, the experimental results demonstrate the efficiency of the proposed non-invasive method. Compared with artificial neural network, the test results also show high accuracy, good adaptability, and faster processing time for the detection of heartbeat signals. PMID:16937172
Cryotherapy of cardiac arrhythmia: From basic science to the bedside.
Avitall, Boaz; Kalinski, Arthur
This review focuses on the basic science of cellular destruction by tissue freezing and application of transvenous cryocatheter technology to treat cardiac arrhythmia. Ideally, foci for arrhythmias are selectively ablated, arrhythmogenic tissues are destroyed, and reentry circuits are bisected in order to silence adverse electrical activity, with the goal of restoring normal sinus rhythm. The mechanism of ablation using cryotherapy results in distinct lesion qualities advantageous to radiofrequency (Khairy P, Chauvet M, Lehman J, et al. Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 2003;107:2045-2050). This review is devoted to the mechanism of cryoablation, postablation histopathological changes, and how this information should be used by the clinicians to improve safety and maximize ablation success. PMID:26031374
Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death.
Davis, A M; Natelson, B H
Neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation. Recognition and analysis of such links in the pathogenesis of malignant cardiac arrhythmia are emphasized in this review. Neurocardiac links have been shown to produce arrhythmia both experimentally and clinically; specific examples, including stroke, epilepsy, and environmental stress are presented. We hypothesize that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmia and sudden cardiac death when the neurocardiac axis is activated. Reviewing possible mechanisms of brain-related arrhythmias, we suggest that the nervous system directs the events leading to cardiac damage by raising catecholamine levels and potentially inducing arrhythmia. PMID:8219819
Cardiac ultrasonography in structural abnormalities and arrhythmias. Recognition and treatment.
Brook, M M; Silverman, N H; Villegas, M
Fetal cardiac ultrasonography has become an important tool in the evaluation of fetuses at risk for cardiac anomalies. It can both guide prenatal treatment and assist the management and timing of delivery. We recommend that a fetal echocardiogram be done when there is a family history of congenital heart disease; maternal disease that may affect the fetus; a history of maternal drug use, either therapeutic or illegal; evidence of other fetal abnormalities; or evidence of fetal hydrops. The optimal timing of evaluation is 18 to 22 weeks' gestation. An entire range of structural cardiac defects can be visualized prenatally, including atrioventricular septal defect, ventricular septal defect, cardiomyopathy, ventricular outlet obstruction, and complex cardiac defects. The outcome for a fetus with a recognized abnormality is unfavourable, with less than 50% surviving the neonatal period. Fetal cardiac arrhythmias are also a common occurrence, 15% in the series described here. Premature atrial or ventricular contractions are most commonly seen and usually require no treatment. Supraventricular tachycardia can result in hydrops and require in utero treatment to prevent fetal demise. Complete heart block, particularly in association with structural heart disease, has a poor prognosis for fetal survival. Images PMID:8236970
Cardiac arrhythmias produced by ultrasound and contrast agents
NASA Astrophysics Data System (ADS)
Rota, Claudio
Ultrasound is used widely in medicine for both diagnostic and therapeutic applications. Ultrasound contrast agents are suspensions of gas-filled microbubbles used to enhance diagnostic imaging. Microbubble contrast agents can increase the likelihood of bioeffects of ultrasound associated with acoustic cavitation. Under certain exposure conditions, the interaction of ultrasound with cardiac tissues can produce cardiac arrhythmias. The general objective of this thesis was to develop a greater understanding of ultrasound-induced premature cardiac beats. The hypothesis guiding this work was that acoustic cavitation is the physical mechanism for the production of arrhythmias with ultrasound. This hypothesis was tested through a series of experiments with mice in vivo and theoretical investigations. Results of this research supported the acoustic cavitation hypothesis. The acoustic pressure threshold for premature beats was significantly lower with microbubble contrast agents present in the blood than without. With microbubbles, the threshold for premature beats was below the current output limits of diagnostic devices. The threshold was not significantly dependent upon contrast agent type and was not influenced by contrast agent dose over three orders of magnitude. Furthermore, the dependence of the threshold on acoustic frequency was consistent with the frequency dependence of acoustic cavitation. Experimentally determined thresholds for premature beats in vivo were in excellent agreement with theoretically estimated thresholds for inertial cavitation. A passive cavitation detector (PCD) was used to measure the acoustic emissions produced by cavitating microbubbles in vivo. A direct correlation between the amplitude of the PCD and the percentage of ultrasound pulses producing a premature beat was consistent with cavitation as a mechanism for this bioeffect. Although this thesis focused on the mechanistic understanding of ultrasound-induced arrhythmias, more persistent
Detection and Prevention of Cardiac Arrhythmias During Space Flight
NASA Technical Reports Server (NTRS)
Pillai, Dilip; Rosenbaum, David S.; Liszka, Kathy J.; York, David W.; Mackin, Michael A.; Lichter, Michael J.
There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Electrical alternans affecting the ST segment and T-wave have been demonstrated to be common among patients at increased risk for ventricular arrhythmias. Subtle electrical alternans on the ECG may serve as a noninvasive marker of vulnerability to ventricular arrhythmias. We are studying indices of electrical instability in the heart for long term space missions by non-invasively measuring microvolt level T-wave alternans in a reduced gravity environment. In this investigation we are using volunteer subjects on the KC-135 aircraft as an initial study of the effect of electrical adaptation of the heart to microgravity. T-wave alternans will be analyzed for heart rate variability and QT restitution curve plotting will be compared for statistical significance.
Introduction: Mapping and control of complex cardiac arrhythmias.
Christini, David J.; Glass, Leon
This paper serves as an introduction to the Focus Issue on mapping and control of complex cardiac arrhythmias. We first introduce basic concepts of cardiac electrophysiology and describe the main clinical methods being used to treat arrhythmia. We then provide a brief summary of the main themes contained in the articles in this Focus Issue. In recent years there have been important advances in the ability to map the spread of excitation in intact hearts and in laboratory settings. This work has been combined with simulations that use increasingly realistic geometry and physiology. Waves of excitation and contraction in the heart do not always propagate with constant velocity but are often subject to instabilities that may lead to fluctuations in velocity and cycle time. Such instabilities are often treated best in the context of simple one- or two-dimensional geometries. An understanding of the mechanisms of propagation and wave stability is leading to the implementation of different stimulation protocols in an effort to modify or eliminate abnormal rhythms. (c) 2002 American Institute of Physics. PMID:12779601
Arrhythmias, Sudden Cardiac Death and incapacitation of pilots
Mantziari, L; Styliadis, C; Kourtidou-Papadeli, C; Styliadis, I
Inflight medical emergencies occur at a rate of 20 to 100 per million passengers, with a death rate of 0.1 to 1 per million. Cardiac, neurologic, and respiratory complaints comprise the more serious emergencies, as defined by aircraft diversion or use of ground-based medical assistance. In this paper, we review changes seen in the resting electrocardiogram in normal individuals exposed to high altitude, alongside important implications for patients with heart diseases in high altitude exposures and the possible effects of high altitude to permanent cardiac pacemakers. Arrhythmias in pilots and public safety are revisited together with the guidelines of the Joint Aviation Requirements (JAR) in Europe. The situation of Military flights is also discussed. Physicians ought to become knowledgeable about the specific medical job standards for their patients when asked to render opinions regarding fitness to fly. A database must be established to obtain prospective data that defines the risk of accidents in patients who are or were being treated for arrhythmias. Current guidelines could then be updated and revised as appropriate. PMID:19050752
Role of CaMKII in cardiac arrhythmias.
Hund, Thomas J; Mohler, Peter J
Protein phosphorylation is a central mechanism in vertebrates for the regulation of signaling. With regard to the cardiovascular system, phosphorylation of myocyte targets is critical for the regulation of excitation contraction coupling, metabolism, intracellular calcium regulation, mitochondrial activity, transcriptional regulation, and cytoskeletal dynamics. In fact, pathways that tune protein kinase signaling have been a mainstay for cardiovascular therapies for the past 60 years. The calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase with numerous roles in human physiology. Dysfunction in CaMKII-based signaling has been linked with a host of cardiovascular phenotypes including heart failure and arrhythmia, and CaMKII levels are elevated in human and animal disease models of heart disease. While nearly a decade has been invested in targeting CaMKII for the treatment of heart failure and arrhythmia phenotypes, to date, approaches to target the molecule for antiarrhythmic benefit have been unsuccessful for reasons that are still not entirely clear, although (1) lack of compound specificity and (2) the multitude of downstream targets are likely contributing factors. This review will provide an update on current pathways regulated by CaMKII with the goal of illustrating potential upstream regulatory mechanisms and downstream targets that may be modulated for the prevention of cardiac electrical defects. While the review will cover multiple aspects of CaMKII dysfunction in cardiovascular disease, we have given special attention to the potential of CaMKII-associated late Na(+) current as a novel therapeutic target for cardiac arrhythmia. PMID:25577293
78 FR 36787 - Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug...
Federal Register 2010, 2011, 2012, 2013, 2014
... HUMAN SERVICES Food and Drug Administration Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia... the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug Development Without the... the current guidelines, and the importance of a uniform assay schema. Date and Time: The...
Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats
Epidemiological studies demonstrate a significant association between cardiac electrical dysfunction, arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electri...
A change in the heart's normal electrical conduction system can result in an arrhythmia or irregular heartbeat. An arrhythmia can be an abnormally slow heartbeat, or an abnormally fast heartbeat. In ...
An arrhythmia is a problem with the rate or rhythm of your heartbeat. It means that your heart beats ... is called bradycardia. The most common type of arrhythmia is atrial fibrillation, which causes an irregular and ...
... from the NHLBI on Twitter. What Is an Arrhythmia? Español An arrhythmia (ah-RITH-me-ah) is a problem with ... rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, ...
Ventricular Arrhythmias in Apparently Normal Hearts: Who Needs an Implantable Cardiac Defibrillator?
Tan, Alex Y; Ellenbogen, Kenneth
Idiopathic ventricular tachycardia is often considered a benign form of ventricular arrhythmia in patients without apparent structural heart disease. However, a subset of patients may develop malignant ventricular arrhythmias and present with syncope and sudden cardiac arrest. Survivors of cardiac arrest are candidates for implantable cardiac defibrillators (ICDs). The indications for ICDs in patients with less than a full-blown cardiac arrest presentation but with electrocardiographically high-risk ectopy features remain uncertain. This article addresses some of the uncertainties and pitfalls in ICD risk stratification in this patient group and explores potential mechanisms for malignant conversion of benign premature ventricular complexes to sustained arrhythmia. PMID:27521094
Exact coherent structures: from fluid turbulence to cardiac arrhythmias
NASA Astrophysics Data System (ADS)
Grigoriev, Roman; Marcotte, Christopher; Byrne, Gregory
Ventricular fibrillation, a life threatening cardiac arrhythmia, is an example of spatiotemporally chaotic state dominated by multiple interacting spiral waves. Recent studies of weak fluid turbulence suggest that spatiotemporal chaos in general can be understood as a walk among exact unstable regular solutions (exact coherent states, ECS) of nonlinear evolution equations. Several classes of ECS are believed to play a dominant role; most typically these are equilibria and periodic orbits or relative equilibria and relative periodic orbits for systems with global continuous symmetries. Numerical methods originally developed in the context of fluid turbulence can also be applied to models of cardiac dynamics which possess translational and rotational symmetries and, indeed, allowed us to identify relative equilibria and periodic orbits describing isolated spirals with, respectively, fixed and drifting cores. In order to find regular solutions featuring multiple interacting spirals a new approach is required that takes into consideration the dynamics of slowly drifting cores associated with local, rather than global, symmetries. We describe how local symmetries can be reduced and more general types of ECS computed that dominate spiral wave chaos in models of cardiac tissue.
A Case for Pharmacogenomics in Management of Cardiac Arrhythmias
Kandoi, Gaurav; Nanda, Anjali; Scaria, Vinod; Sivasubbu, Sridhar
Disorders of the cardiac rhythm are quite prevalent in clinical practice. Though the variability in drug response between individuals has been extensively studied, this information has not been widely used in clinical practice. Rapid advances in the field of pharmacogenomics have provided us with crucial insights on inter-individual genetic variability and its impact on drug metabolism and action. Technologies for faster and cheaper genetic testing and even personal genome sequencing would enable clinicians to optimize prescription based on the genetic makeup of the individual, which would open up new avenues in the area of personalized medicine. We have systematically looked at literature evidence on pharmacogenomics markers for anti-arrhythmic agents from the OpenPGx consortium collection and reason the applicability of genetics in the management of arrhythmia. We also discuss potential issues that need to be resolved before personalized pharmacogenomics becomes a reality in regular clinical practice. PMID:22557843
Role of ATP-sensitive K+ channels in cardiac arrhythmias.
Nakaya, Haruaki
The sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) (sarcKATP) channel in the heart is a hetero-octamer comprising the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor SUR2A. By functional analysis of genetically engineered mice lacking sarcKATP channels, the pathophysiological roles of the K(+) channel in the heart have been extensively evaluated. Although mitochondrial KATP (mitoKATP) channel is proposed to be an important effector for the protection of ischemic myocardium and the inhibition of ischemia/reperfusion-induced ventricular arrhythmias, the molecular identity of mitoKATP channel has not been established. Although selective sarcKATP-channel blockers can prevent ischemia/reperfusion-induced ventricular arrhythmias by inhibiting the action potential shortening in the acute phase, the drugs may aggravate the ischemic damages due to intracellular Ca(2+) overload. The sarcKATP channel is also mandatory for optimal adaptation to hemodynamic stress such as sympathetic activation. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. Recently, it has been proposed that the gain-of-function mutation of cardiac Kir6.1 channel can be a pathogenic substrate for J wave syndromes, a cause of idiopathic ventricular fibrillation as early repolarization syndrome or Brugada syndrome, whereas loss of function of the channel mutations can underlie sudden infant death syndrome. However, precise role of Kir6.1 channels in cardiac cells remains to be defined and further study may be needed to clarify the role of Kir6.1 channel in the heart. PMID:24367007
Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.
Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe
As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space. PMID:24211993
Detection and Prevention of Cardiac Arrhythmias During Space Flight
NASA Technical Reports Server (NTRS)
Pillai, Dilip; Rosenbaum, David S.; Liszka, Kathy J.; York, David W.; Mackin, Michael A.; Lichter, Michael J.
There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.
Cardiac arrhythmias associated with a liquid protein diet for the treatment of obesity
Lantigua, R.A.; Amatruda, J.M.; Biddle, T.L.; Forbes, G.B.; Lockwood, D.H.
Our data demonstrate that a liquid protein diet is frequently associated with potentially life-threatening arrhythmias that are not detected on routine electrocardiography. Several studies of metabolic balance failed to reveal a cause for these arrhythmias. We recommended that the use of liquid protein diets should be terminated pending further investigation of the causes and prevention of the cardiac toxicity.
Getting your signals straight. Comparing radio-frequency ablation and cryoablation for treating cardiac arrhythmias.
Radio-frequency ablation has proven to be an effective method for treating cardiac arrhythmias. However, a newer treatment method called cryoablation is becoming increasingly popular. In this article, we discuss the advantages and disadvantages of each. PMID:21305902
Proton Pump Inhibitor Use Is not Associated with Cardiac Arrhythmia in Critically Ill Patients
Chen, Kenneth P.; Lee, Joon; Mark, Roger G.; Feng, Mornin; Celi, Leo A.; Danziger, John
Hypomagnesemia can lead to cardiac arrhythmias. Recently, observational data has linked chronic proton pump inhibitor (PPI) exposure to hypomagnesemia. Whether PPI exposure increases the risk for arrhythmias has not been well studied. Using a large, single center inception cohort of critically ill patients, we examined whether PPI exposure was associated with admission electrocardiogram (ECG) readings of a cardiac arrhythmia in over 8000 patients. There were 24.5% PPI users while 6% were taking a histamine 2 antagonist. 14.3% had a cardiac arrhythmia. PPI use was associated with a 1.18 (95% CI=1.02–1.36, p=0.02) unadjusted and 0.96 (95% CI=0.83–1.12, p=0.62) adjusted risk of arrhythmia. Amongst diuretic users (n=2468), PPI use was similarly not associated with an increased risk of cardiac arrhythmia. In summary, in a large cohort of critically ill patients, PPI exposure is not associated with an increased risk of cardiac arrhythmia. PMID:25655574
... beats too quickly, too slowly, or with an irregular pattern. When the heart beats faster than normal, ... of arrhythmia is atrial fibrillation, which causes an irregular and fast heart beat. Many factors can affect ...
Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.
Navas de Solis, C
Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. PMID:27156002
Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract
Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...
Recommendations of the Brazilian Society of Cardiac Arrhythmias for Holter Monitoring Services
Lorga Filho, Adalberto; Cintra, Fatima Dumas; Lorga, Adalberto; Grupi, Cesar José; Pinho, Claudio; Moreira, Dalmo Antonio Ribeiro; Sobral Filho, Dario C.; de Brito, Fabio Sandoli; Kruse, José Claudio Lupi; Neto, José Sobral
Background There are innumerous indicators to assure the quality of a service. However, medical competence and the proper performance of a procedure determine its final quality. The Brazilian Society of Cardiac Arrhythmias recommends minimum parameters necessary to guarantee the excellence of ambulatory electrocardiographic monitoring services. Objective To recommend minimum medical competences and the information required to issue a Holter monitoring report. Methods This study was grounded in the concept of evidence-based medicine and, when evidence was not available, the opinion of a writing committee was used to formulate the recommendation. That committee consisted of professionals with experience on the difficulties of the method and management in providing services in that area. Results The professional responsible for the Holter monitoring analysis should know cardiovascular pathologies and have consistent formation on electrocardiography, including cardiac arrhythmias and their differential diagnoses. The report should be written in a clear and objective way. The minimum parameters that comprise a Holter report should include statistics of the exam, as well as quantification and analysis of the rhythm disorders observed during monitoring. Conclusion Ambulatory electrocardiographic monitoring should be performed by professionals knowledgeable about electrocardiographic analysis, whose report should comprise the minimum parameters mentioned in this document. PMID:24030077
Unveiling specific triggers and precipitating factors for fatal cardiac events in inherited arrhythmia syndromes.
Nakajima, Tadashi; Kaneko, Yoshiaki; Kurabayashi, Masahiko
Patients with inherited arrhythmia syndromes, such as long QT syndrome, Brugada syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, and their latent forms, are at risk for fatal arrhythmias. These diseases are typically associated with genetic mutations that perturb cardiac ionic currents. The analysis of cardiac events by genotype-phenotype correlation studies has revealed that fatal arrhythmias in some genotypes are triggered by physical or emotional stress, and those in the others are more likely to occur during sleep or at rest. Thus, the risk stratification and management of affected patients differ strikingly according to the genetic variant of the inherited arrhythmia syndrome. Risk stratification may be further refined by considering the precipitating factors, such as drugs, bradycardia, electrolyte disturbances, fever, and cardiac memory. Moreover, an increasing number of studies imply that the susceptibility of fatal arrhythmias in patients with acute coronary syndrome or takotsubo cardiomyopathy is at least partly ascribed to the genetic variants causing inherited arrhythmia syndromes. In this article, we review the recent advances in the understanding of the molecular genetics and genotype-phenotype correlations in inherited arrhythmia syndromes and consider the triggers and precipitating factors for fatal arrhythmias in these disorders. Further studies to explore the triggers and precipitating factors specific to the genotypes and diseases are needed for better clinical management. PMID:25925977
The electrocardiogram in the assessment of the effect of drugs on cardiac arrhythmias.
Reid, D S
The search for the ideal antiarrhythmic drug continues since none of the available agents offers optimum antiarrhythmic therapy. The continuing search coupled with the interest in the mechanisms of cardiac arrhythmias has led to the development of new techniques for the study of arrhythmias and antiarrhythmic drugs. In this article it is proposed to discuss the electrocardiographic methods used in the assessment of antiarrhythmic drugs. Firstly, to discuss the electrocardiogram in the assessment of the clinical electrophysiological properties of a drug and secondly, the electrocardiogram in the assessment of the value of the drug in the management of cardiac arrhythmias in man. PMID:365208
Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction.
Li, Chang-Yi; Li, Yi-Gang
Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403
Cardiac Sympathetic Nerve Sprouting and Susceptibility to Ventricular Arrhythmias after Myocardial Infarction
Li, Chang-Yi; Li, Yi-Gang
Ventricular arrhythmogenesis is thought to be a common cause of sudden cardiac death following myocardial infarction (MI). Nerve remodeling as a result of MI is known to be an important genesis of life-threatening arrhythmias. It is hypothesized that neural modulation might serve as a therapeutic option of malignant arrhythmias. In fact, left stellectomy or β-blocker therapy is shown to be effective in the prevention of ventricular tachyarrhythmias (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD) after MI both in patients and in animal models. Results from decades of research already evidenced a positive relationship between abnormal nerve density and ventricular arrhythmias after MI. In this review, we summarized the molecular mechanisms involved in cardiac sympathetic rejuvenation and mechanisms related to sympathetic hyperinnervation and arrhythmogenesis after MI and analyzed the potential therapeutic implications of nerve sprouting modification for ventricular arrhythmias and SCD control. PMID:26793403
The influence of motor activity on the development of cardiac arrhythmias during experimental emotional stress
NASA Technical Reports Server (NTRS)
Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.
Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.
Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans
NASA Technical Reports Server (NTRS)
Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.
Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.
The role of the Arrhythmia Team, an integrated, multidisciplinary approach to treatment of patients with cardiac arrhythmias: results of the European Heart Rhythm Association survey.
Fumagalli, Stefano; Chen, Jian; Dobreanu, Dan; Madrid, Antonio Hernandez; Tilz, Roland; Dagres, Nikolaos
Management of patients with cardiac arrhythmias is increasingly complex because of continuous technological advance and multifaceted clinical conditions associated with ageing of the population, the presence of co-morbidities and the need for polypharmacy. The aim of this European Heart Rhythm Association Scientific Initiatives Committee survey was to provide an insight into the role of the Arrhythmia Team, an integrated, multidisciplinary approach to management of patients with cardiac arrhythmias. Forty-eight centres from 18 European countries replied to the Web-based questionnaire. The presence of an Arrhythmia Team was reported by 44% of the respondents, whereas 17% were not familiar with this term. Apart from the electrophysiologist, health professionals who should belong to such teams, according to the majority of the respondents, include a clinical cardiologist, a nurse, a cardiac surgeon, a heart failure specialist, a geneticist, and a geriatrician. Its main activity should be dedicated to the management of patients with complex clinical conditions or refractory or inherited forms of arrhythmias. When present, the Arrhythmia Team was considered helpful by 95% of respondents; the majority of centres (79%) agreed that it should be implemented. The Arrhythmia Team seems to be connected to important expectations in the management of cardiac arrhythmias. The efficacy of such an integrated and multidisciplinary approach should be encouraged and tested in clinical practice. PMID:27174994
... chambers. The walls of the heart squeeze together (contract) to push blood through the chambers. The contractions ... heart beats too slowly. Cardiac defibrillation (very brief electric shock) can be used to stop an abnormal ...
Next Generation Sequencing for the Diagnosis of Cardiac Arrhythmia Syndromes
Lubitz, Steven A.; Ellinor, Patrick T.
Inherited arrhythmia syndromes are collectively associated with substantial morbidity, yet our understanding of the genetic architecture of these conditions remains limited. Recent technological advances in DNA sequencing have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next generation sequencing allows the large-scale and rapid assessment of entire genomes. Although next generation sequencing represents a major technological advance, it has introduced numerous challenges with respect to the interpretation of genetic variation, and has opened a veritable floodgate of biological data of unknown clinical significance to practitioners. In this review, we discuss current genetic testing indications for inherited arrhythmia syndromes, broadly outline characteristics of next generation sequencing techniques, and highlight challenges associated with such testing. We further summarize future directions that will be necessary to address to enable the widespread adoption of next generation sequencing in the routine management of patients with inherited arrhythmia syndromes. PMID:25625719
Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias
Hasan, Wohaib; Streiff, Cole T.; Houle, Jennifer C.; Woodward, William R.; Giraud, George D.; Brooks, Virginia L.; Habecker, Beth A.
Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250–275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events. PMID:24014675
Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?
Ruenraroengsak, Pakatip; Shevchuk, Andrew I; Korchev, Yuri E; Lab, Max J; Tetley, Teresa D; Gorelik, Julia
Aim To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. Materials & methods Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp. Results Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. By contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50–250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores. Conclusion The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias. PMID:23140503
Fetal cardiac arrhythmia detection and in utero therapy
Strasburger, Janette F.; Wakai, Ronald T.
The human fetal heart develops arrhythmias and conduction disturbances in response to ischemia, inflammation, electrolyte disturbances, altered load states, structural defects, inherited genetic conditions, and many other causes. Yet sinus rhythm is present without altered rate or rhythm in some of the most serious electrophysiological diseases, which makes detection of diseases of the fetal conduction system challenging in the absence of magnetocardiographic or electrocardiographic recording techniques. Life-threatening changes in QRS or QT intervals can be completely unrecognized if heart rate is the only feature to be altered. For many fetal arrhythmias, echocardiography alone can assess important clinical parameters for diagnosis. Appropriate treatment of the fetus requires awareness of arrhythmia characteristics, mechanisms, and potential associations. Criteria to define fetal bradycardia specific to gestational age are now available and may allow detection of ion channelopathies, which are associated with fetal and neonatal bradycardia. Ectopic beats, once thought to be entirely benign, are now recognized to have important pathologic associations. Fetal tachyarrhythmias can now be defined precisely for mechanism-specific therapy and for subsequent monitoring of response. This article reviews the current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia. PMID:20418904
Non-Linear Dynamics of Cardiac Alternans: Subcellular to Tissue-Level Mechanisms of Arrhythmia
Gaeta, Stephen A.; Christini, David J.
Cardiac repolarization alternans is a rhythm disturbance of the heart in which rapid stimulation elicits a beat-to-beat alternation in the duration of action potentials and magnitude of intracellular calcium transients in individual cardiac myocytes. Although this phenomenon has been identified as a potential precursor to dangerous reentrant arrhythmias and sudden cardiac death, significant uncertainty remains regarding its mechanism and no clinically practical means of halting its occurrence or progression currently exists. Cardiac alternans has well-characterized tissue, cellular, and subcellular manifestations, the mechanisms and interplay of which are an active area of research. PMID:22783195
Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model
Balakrishnan, Minimol; Chakravarthy, V. Srinivasa; Guhathakurta, Soma
Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias. PMID:26733873
Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model.
Balakrishnan, Minimol; Chakravarthy, V Srinivasa; Guhathakurta, Soma
Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias. PMID:26733873
Congenital Deafness with Cardiac Arrhythmias: The Jervell and Lange-Nielsen Syndrome.
ERIC Educational Resources Information Center
Wahl, Richard A.; Macdonald, Dick, II
The Jervell and Lange-Nielsen syndrome, affecting 0.3 percent of congenitally deaf persons, consists of severe cardiac arrhythmias and sensorineural hearing loss. The authors recommend that every congenitally deaf child with suspicious symptoms receive an electrocardiogram and that professionals who work with deaf children not only inform…
Cardiac arrhythmia classification using multi-modal signal analysis.
Kalidas, V; Tamil, L S
In this paper, as a contribution to the Physionet/Computing in Cardiology 2015 Challenge, we present individual algorithms to accurately classify five different life threatening arrhythmias with the goal of suppressing false alarm generation in intensive care units. Information obtained by analysing electrocardiogram, photoplethysmogram and arterial blood pressure signals was utilized to develop the classification models. Prior to classification, the signals were subject to a signal pre-processing stage for quality analysis. Classification was performed using a combination of support vector machine based machine learning approach and logical analysis techniques. The predicted result for a certain arrhythmia classification model was verified by logical analysis to aid in reduction of false alarms. Separate feature vectors were formed for predicting the presence or absence of each arrhythmia, using both spectral and time-domain information. The training and test data were obtained from the Physionet/CinC Challenge 2015 database. Classification algorithms were written for two different categories of data, namely real-time and retrospective, whose data lengths were 10 s and an additional 30 s, respectively. For the real-time test dataset, sensitivity of 94% and specificity of 82% were obtained. Similarly, for the retrospective test dataset, sensitivity of 94% and specificity of 86% were obtained. PMID:27454417
Pharmacy Students' Performance and Perceptions in a Flipped Teaching Pilot on Cardiac Arrhythmias
Ip, Eric J.; Lopes, Ingrid; Rajagopalan, Vanishree
Objective. To implement the flipped teaching method in a 3-class pilot on cardiac arrhythmias and to assess the impact of the intervention on academic performance and student perceptions. Design. An intervention group of 101 first-year pharmacy students, who took the class with the flipped teaching method, were supplied with prerecorded lectures prior to their 3 classes (1 class in each of the following subjects: basic sciences, pharmacology, and therapeutics) on cardiac arrhythmias. Class time was focused on active-learning and case-based exercises. Students then took a final examination that included questions on cardiac arrhythmias. The examination scores of the intervention group were compared to scores of the Spring 2011 control group of 105 first-year students who took the class with traditional teaching methods. An online survey was conducted to assess student feedback from the intervention group. Assessment. The mean examination scores of the intervention group were significantly higher than the mean examination scores of the control group for the cardiac arrhythmia classes in pharmacology (with 89.6 ± 2.0% vs 56.8 ± 2.2%, respectively) and therapeutics (89.2 ± 1.4% vs 73.7 ± 2.1%, respectively). The survey indicated higher student satisfaction for flipped classes with highly rated learning objectives, recordings, and in-class activities. Conclusion. Use of the flipped teaching method in a 3-class pilot on cardiac arrhythmias improved examination scores for 2 of the 3 classes (pharmacology and therapeutics). Student satisfaction was influenced by the quality of the learning objectives, prerecorded lectures, and inclass active-learning activities. PMID:25657372
Postoperative arrhythmias after cardiac surgery: incidence, risk factors, and therapeutic management.
Peretto, Giovanni; Durante, Alessandro; Limite, Luca Rosario; Cianflone, Domenico
Arrhythmias are a known complication after cardiac surgery and represent a major cause of morbidity, increased length of hospital stay, and economic costs. However, little is known about incidence, risk factors, and treatment of early postoperative arrhythmias. Both tachyarrhythmias and bradyarrhythmias can present in the postoperative period. In this setting, atrial fibrillation is the most common heart rhythm disorder. Postoperative atrial fibrillation is often self-limiting, but it may require anticoagulation therapy and either a rate or rhythm control strategy. However, ventricular arrhythmias and conduction disturbances can also occur. Sustained ventricular arrhythmias in the recovery period after cardiac surgery may warrant acute treatment and long-term preventive strategy in the absence of reversible causes. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur with the need for permanent pacing. We provide a complete and updated review about mechanisms, risk factors, and treatment strategies for the main postoperative arrhythmias. PMID:24511410
Postoperative Arrhythmias after Cardiac Surgery: Incidence, Risk Factors, and Therapeutic Management
Cianflone, Domenico
Arrhythmias are a known complication after cardiac surgery and represent a major cause of morbidity, increased length of hospital stay, and economic costs. However, little is known about incidence, risk factors, and treatment of early postoperative arrhythmias. Both tachyarrhythmias and bradyarrhythmias can present in the postoperative period. In this setting, atrial fibrillation is the most common heart rhythm disorder. Postoperative atrial fibrillation is often self-limiting, but it may require anticoagulation therapy and either a rate or rhythm control strategy. However, ventricular arrhythmias and conduction disturbances can also occur. Sustained ventricular arrhythmias in the recovery period after cardiac surgery may warrant acute treatment and long-term preventive strategy in the absence of reversible causes. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur with the need for permanent pacing. We provide a complete and updated review about mechanisms, risk factors, and treatment strategies for the main postoperative arrhythmias. PMID:24511410
New directions in cardiac arrhythmia management: present challenges and future solutions.
Nattel, Stanley; Andrade, Jason; Macle, Laurent; Rivard, Lena; Dyrda, Katia; Mondesert, Blandine; Khairy, Paul
Cardiac arrhythmias are a major contributor to population morbidity and mortality. Enormous advances in arrhythmia management have occurred over the 60 years since the founding of the Montreal Heart Institute, but important challenges remain. The purpose of this article is to identify the areas of cardiac arrhythmia therapy that need improvement and to discuss the evolving approaches that promise solutions. Challenges in diagnosis, detection, and risk-stratification include difficulties in separating benign from high-risk syncope and pinpointing the underlying causes, the detection of silent atrial fibrillation in patients at risk of stroke, and inadequate identification of sudden-death risk. Implantable devices are limited by the need for battery and device replacements, device complications like infection and dysfunction, and lead complications like fracture, infection, or displacement. Antiarrhythmic drug therapy, although widely used, is plagued by a very limited range of available agents, supply issues, insufficient efficacy, and significant adverse effect risk. Health economic concerns include the high cost of new technologies, challenges in establishing cost effectiveness, and restrictive practices of government or third-party payers. Major improvements in arrhythmia management can be expected from new discoveries and technological developments in genetics, innovative diagnostic tools for arrhythmia monitoring, imaging and analysis, new approaches to antiarrhythmic drug development, biological therapies, and continuing improvement in implantable device technology like further miniaturization, leadless technology, and use of novel energy sources. As exciting as the developments in arrhythmia management have been in the past, we can look forward to exponential improvement in our ability to manage arrhythmia patients in the near future. PMID:25432137
Cardiac bidomain bath-loading effects during arrhythmias: interaction with anatomical heterogeneity.
Bishop, Martin J; Vigmond, Edward; Plank, Gernot
Cardiac tissue is always surrounded by conducting fluid, both in vivo (blood) and in experimental preparations (Tyrode's solution), which acts to increase conduction velocity (CV) close to the tissue-fluid interface, inducing transmural wavefront curvature. Despite its potential importance, computer modeling studies focused on arrhythmia mechanisms have previously not accounted for these bath-loading effects. Here, we investigate the increase in CV and concomitant change in transmural wavefront profiles upon both propagation and arrhythmia dynamics within models of differing anatomical complexity. In simplified slab models, in absence of transmural fiber rotation, bath-loading induced transmural wavefront curvature dominates, significantly increasing arrhythmia complexity compared to no bath. In the presence of fiber rotation, bath-loading effects are less striking and depend upon propagation direction: the bath accentuates natural concave curvature caused by transmurally rotating fibers, but attenuates convex curvature, which negates overall impact upon arrhythmia complexity. Finally, we demonstrate that the high degree of anatomical complexity within whole ventricular models modulates bath-loading induced transmural wavefront curvature. However, key is the increased surface CV that dramatically reduces both arrhythmia inducibility and resulting complexity by increasing wavelength and reducing the available excitable gap. Our findings highlight the importance of including bath-loading effects during arrhythmia mechanism investigations, which could have implications for interpreting and comparing simulation results with experimental data where such effects are inherently present. PMID:22208185
Frequency of cardiac arrhythmias in high- and low- yielding dairy cows
Jafari Dehkordi, Afshin; Nasser Mohebi, Abdonnaser; Heidari Soreshjani, Masoumeh
Electrocardiography (ECG) may be used to recognize cardiac disorders. Levels of milk production may change the serum electrolytes which its imbalance has a role in cardiac arrhythmia. Fifty high yielding and fifty low yielding Holstein dairy cows were used in this study. Electrocardiography was recorded by base-apex lead and blood samples were collected from jugular vein for measurement of serum elements such as sodium, potassium, calcium, phosphorous, iron and magnesium. Cardiac dysrhythmias were detected more frequent in low yielding Holstein cows (62.00%) compared to high yielding Holstein cows (46.00%). The cardiac dysrhythmias that were observed in low yielding Holstein cows included sinus arrhythmia (34.70%), wandering pacemaker (22.45 %), bradycardia (18.37%), tachycardia (10.20%), atrial premature beat (2.04%), sinoatrial block (2.04%), atrial fibrillation (8.16%) and atrial tachycardia (2.04%). The cardiac dysrhythmias were observed in high yielding Holstein cows including, sinus arrhythmia (86.95%) and wandering pacemaker (13.05%). Also, notched P wave was observed to be 30% and 14% in high- and low- yielding Holstein cows respectively. The serum calcium concentration of low yielding Holstein cows was significantly lower than that of high yielding Holstein cows. There was not any detectable significant difference in other serum elements between high- and low- yielding Holstein cows. Based on the result of present study, could be concluded that low serum concentration of calcium results to more frequent dysrhythmias in low yielding Holstein cows. PMID:25568685
Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias?
Cagnoni, Francesca; Destro, Maurizio; Bontempelli, Erika; Locatelli, Giovanni; Hering, Dagmara; Schlaich, Markus P
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias. PMID:26781253
Ischemic, genetic and pharmacological origins of cardiac arrhythmias: The contribution of the Quebec Heart Institute
Drolet, Benoît; Simard, Chantale; Gailis, Laimonis; Daleau, Pascal
Research in the field of basic electrophysiology at the Quebec Heart Institute (Laval Hospital, Quebec City, Quebec) has evolved since its beginning in the 1990s. Interests were focused on cardiac arrhythmias induced by drugs, allelic variants and metabolic factors produced during ischemia. The results have contributed to the creation of new standards in drug development, more specifically, testing all new drugs for their potential effects on cardiac potassium currents, which could produce life-threatening proarrhythmic effects. In a French-Canadian population, three heterozygous single nucleotide polymorphisms in hKv1.5, a gene encoding for a major atrial repolarizing current, were found. These variants affect the expression level of the hKv1.5 channel and change the inactivation process in the presence of its accessory beta subunit. Because these effects could shorten atrial action potential, their presence was tested in postcoronary bypass patients and a higher prevalence was found in patients with postoperative atrial fibrillation. Finally, three potentially proarrhythmic factors characteristic of ischemia were identified: pH decrease; oxygen free radicals, which both increase the flow of K+ ions through human ether-a-go-go-related gene and hKv1.5, producing a reduction in action potential duration, frequently leading to cardiac arrhythmias; and lysophosphatidylcholine, a metabolite involved in the production of cardiac arrhythmias early during ischemia that was shown to be a major cause of electrical uncoupling. Over the past decade, the Quebec Heart Institute has provided a significant amount of original data in the field of basic cardiac electrophysiology, specifically concerning arrhythmias originating from pharmacological agents, genetic background and cardiac ischemia. PMID:17932583
Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data
Hennessy, Sean; Bilker, Warren B; Knauss, Jill S; Margolis, David J; Kimmel, Stephen E; Reynolds, Robert F; Glasser, Dale B; Morrison, Mary F; Strom, Brian L
Objective To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. Design Cohort study of outpatients using administrative data. Setting 3 US Medicaid programmes. Participants Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. Main outcome measure Diagnosis of cardiac arrest or ventricular arrhythmia. Results Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses ⩾600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). Conclusions The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect. What is already known on this topicThioridazine seems to prolong the electrocardiographic QT interval more than haloperidolAlthough QT prolongation is used as a marker of arrhythmogenicity, it is unknown whether thioridazine is any worse than haloperidol with regard to cardiac safetyWhat this study addsPatients taking antipsychotic drugs had higher risks of cardiac events than control patients with glaucoma or psoriasisOverall, the risk of cardiac arrest and ventricular arrhythmia was not higher with thioridazine than haloperidolThioridazine may
Defects in Cytoskeletal Signaling Pathways, Arrhythmia, and Sudden Cardiac Death
Smith, Sakima; Curran, Jerry; Hund, Thomas J.; Mohler, Peter J.
Ankyrin polypeptides are cellular adapter proteins that tether integral membrane proteins to the cytoskeleton in a host of human organs. Initially identified as integral components of the cytoskeleton in erythrocytes, a recent explosion in ankyrin research has demonstrated that these proteins play prominent roles in cytoskeletal signaling pathways and membrane protein trafficking/regulation in a variety of excitable and non-excitable cells including heart and brain. Importantly, ankyrin research has translated from bench to bedside with the discovery of human gene variants associated with ventricular arrhythmias that alter ankyrin–based pathways. Ankyrin polypeptides have also been found to play an instrumental role in various forms of sinus node disease and atrial fibrillation (AF). Mouse models of ankyrin-deficiency have played fundamental roles in the translation of ankyrin-based research to new clinical understanding of human sinus node disease, AF, and ventricular tachycardia. PMID:22586405
Current and future modalities of catheter ablation for the treatment of cardiac arrhythmias.
Haines, D E
Catheter ablation has proven to be a safe and effective treatment for a wide variety of cardiac arrhythmias. By destroying the critical zone of conductive tissue responsible for impulse generation or propagation, the arrhythmias may be cured. A variety of modalities of catheter ablation have been tested in the past decade. Initially, high energy direct current shocks delivered through a conventional electrode catheter were used. Now, use of radiofrequency energy as a power supply has resulted in higher efficacy and much improved safety of this technique. New approaches including low energy direct current shock ablation, microwave hyperthermic ablation, and laser photocoagulation are being tested, and may result in further refinement of nonsurgical curative therapy of arrhythmias. PMID:10147817
Control of Cardiac Arrhythmia by Nonlinear Spatiotemporal Delayed Feedback
NASA Astrophysics Data System (ADS)
Boroujeni, Forough Rezaei; Vasegh, Nastaran; Sedigh, Ali Khaki
The dynamic feedback control of the cardiac pacing interval has been widely used to suppress alternans. In this paper, temporally and spatially suppressing the alternans for cardiac tissue consisting of a one-dimensional chain of cardiac units is investigated. The model employed is a nonlinear partial difference equation. The model's fixed points and their stability conditions are determined, and bifurcations and chaos phenomenon have been studied by numerical simulations. The main objective of this paper is to stabilize the unstable fixed point of the model. The proposed approach is nonlinear spatiotemporal delayed feedback, and the appropriate interval for controller feedback gain is calculated using the linear stability analysis. It is proven that the proposed approach is robust with respect to all bifurcation parameter variations. Also, set point tracking is achieved by employing delayed feedback with an integrator. Finally, simulation results are provided to show the effectiveness of the proposed methodology.
Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation.
Pei, Zifan; Xiao, Yucheng; Meng, Jingwei; Hudmon, Andy; Cummins, Theodore R
Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration. In contrast, blocking palmitoylation increases closed-state channel inactivation and reduces myocyte excitability. We identify four cysteines as possible Nav1.5 palmitoylation substrates. A mutation of one of these is associated with cardiac arrhythmia (C981F), induces a significant enhancement of channel closed-state inactivation and ablates sensitivity to depalmitoylation. Our data indicate that alterations in palmitoylation can substantially control Nav1.5 function and cardiac excitability and this form of post-translational modification is likely an important contributor to acquired and congenital arrhythmias. PMID:27337590
Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation
Pei, Zifan; Xiao, Yucheng; Meng, Jingwei; Hudmon, Andy; Cummins, Theodore R.
Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration. In contrast, blocking palmitoylation increases closed-state channel inactivation and reduces myocyte excitability. We identify four cysteines as possible Nav1.5 palmitoylation substrates. A mutation of one of these is associated with cardiac arrhythmia (C981F), induces a significant enhancement of channel closed-state inactivation and ablates sensitivity to depalmitoylation. Our data indicate that alterations in palmitoylation can substantially control Nav1.5 function and cardiac excitability and this form of post-translational modification is likely an important contributor to acquired and congenital arrhythmias. PMID:27337590
Online cardiac arrhythmia classification by means of circle maps analysis implemented on an intelligent miniaturized sensor.
Schiek, Michael; Schlösser, Mario; Schnitzer, Andreas; Ying, Hong
The intermittent occurrence of cardiac arrhythmias like e.g. atrial fibrillation hampers their diagnosis and hence the treatment. Since persons suffering from atrial fibrillation are known to have a remarkable increased risk of stroke the diagnosis of atrial fibrillation is a matter of great importance. Easy and comfortable to use long term ECG recording systems capable of online arrhythmia classification might help to solve this problem. We developed an intelligent, miniaturized, and wireless networking sensor which allows lossless local data recordings up to 4 GB. With its outer dimensions of 20mm per rim and less than 15g of weight including the Lithium-Ion battery our modular designed sensor node is thoroughly capable of up to eight channel recordings with 8 kHz sample rate each and provides sufficient computational power for online digital signal processing. For online arrhythmia classification we will record one ECG channel and 3-axis accelerometer data with 512 Hz each, the later being used for activity classification based artifact identification. We adapted our recently developed circle maps analysis of short term heart rate variation to run on this miniaturized intelligent sensor powered by the Texas Instruments MSP430 microcontroller derivate F1611. With this configuration we started to evaluate the cardiac arrhythmia classification in long term ECG recordings. PMID:19162988
Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in β-Thalassemia Major Patients.
Russo, Vincenzo; Rago, Anna; Papa, Andrea Antonio; Nigro, Gerardo
Beta-thalassemia major (β-TM) is a genetic hemoglobin disorder characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Clinical management of thalassemia major consists in regular long-life red blood cell transfusions and iron chelation therapy to remove iron introduced in excess with transfusions. Iron deposition in combination with inflammatory and immunogenic factors is involved in the pathophysiology of cardiac dysfunction in these patients. Heart failure and arrhythmias, caused by myocardial siderosis, are the most important life-limiting complications of iron overload in beta-thalassemia patients. Cardiac complications are responsible for 71% of global death in the beta-thalassemia major patients. The aim of this review was to describe the most frequent electrocardiographic abnormalities and arrhythmias observed in β-TM patients, analyzing their prognostic impact and current treatment strategies. PMID:27324981
Mouse Models of SCN5A-Related Cardiac Arrhythmias
Derangeon, Mickael; Montnach, Jérôme; Baró, Isabelle; Charpentier, Flavien
Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na+ channel NaV1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, a trial standstill, and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This review presents the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. This includes two models knocked out for Nav1.5 β1 and β3 auxiliary subunits that are also discussed. Despite their own limitations that we point out, the mouse models still appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodeling of other genes. This points out the potential role of these genes in the overall human phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity. PMID:22737129
Cell and gene therapy for arrhythmias: Repair of cardiac conduction damage
Xiao, Yong-Fu
Action potentials generated in the sinoatrial node (SAN) dominate the rhythm and rate of a healthy human heart. Subsequently, these action potentials propagate to the whole heart via its conduction system. Abnormalities of impulse generation and/or propagation in a heart can cause arrhythmias. For example, SAN dysfunction or conduction block of the atrioventricular node can lead to serious bradycardia which is currently treated with an implanted electronic pacemaker. On the other hand, conduction damage may cause reentrant tachyarrhythmias which are primarily treated pharmacologically or by medical device-based therapies, including defibrillation and tissue ablation. However, drug therapies sometimes may not be effective or are associated with serious side effects. Device-based therapies for cardiac arrhythmias, even with well developed technology, still face inadequacies, limitations, hardware complications, and other challenges. Therefore, scientists are actively seeking other alternatives for antiarrhythmic therapy. In particular, cells and genes used for repairing cardiac conduction damage/defect have been investigated in various studies both in vitro and in vivo. Despite the complexities of the excitation and conduction systems of the heart, cell and gene-based strategies provide novel alternatives for treatment or cure of cardiac arrhythmias. This review summarizes some highlights of recent research progress in this field. PMID:22783301
Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest
Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting
Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis. PMID:26379761
A Real-Time Cardiac Arrhythmia Classification System with Wearable Sensor Networks
Hu, Sheng; Wei, Hongxing; Chen, Youdong; Tan, Jindong
Long term continuous monitoring of electrocardiogram (ECG) in a free living environment provides valuable information for prevention on the heart attack and other high risk diseases. This paper presents the design of a real-time wearable ECG monitoring system with associated cardiac arrhythmia classification algorithms. One of the striking advantages is that ECG analog front-end and on-node digital processing are designed to remove most of the noise and bias. In addition, the wearable sensor node is able to monitor the patient's ECG and motion signal in an unobstructive way. To realize the real-time medical analysis, the ECG is digitalized and transmitted to a smart phone via Bluetooth. On the smart phone, the ECG waveform is visualized and a novel layered hidden Markov model is seamlessly integrated to classify multiple cardiac arrhythmias in real time. Experimental results demonstrate that the clean and reliable ECG waveform can be captured in multiple stressed conditions and the real-time classification on cardiac arrhythmia is competent to other workbenches. PMID:23112746
Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias
NASA Technical Reports Server (NTRS)
Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.
Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.
Role for the Unfolded Protein Response in Heart Disease and Cardiac Arrhythmias
Liu, Man; Dudley, Samuel C.
The unfolded protein response (UPR) has been extensively investigated in neurological diseases and diabetes, while its function in heart disease is less well understood. Activated UPR participates in multiple cardiac conditions and can either protect or impair heart function. Recently, the UPR has been found to play a role in arrhythmogenesis during human heart failure by affecting cardiac ion channels expression, and blocking UPR has an antiarrhythmic effect. This review will discuss the rationale for and challenges to targeting UPR in heart disease for treatment of arrhythmias. PMID:26729106
Chaos for cardiac arrhythmias through a one-dimensional modulation equation for alternans
Dai, Shu; Schaeffer, David G.
Instabilities in cardiac dynamics have been widely investigated in recent years. One facet of this work has studied chaotic behavior, especially possible correlations with fatal arrhythmias. Previously chaotic behavior was observed in various models, specifically in the breakup of spiral and scroll waves. In this paper we study cardiac dynamics and find spatiotemporal chaotic behavior through the Echebarria–Karma modulation equation for alternans in one dimension. Although extreme parameter values are required to produce chaos in this model, it seems significant mathematically that chaos may occur by a different mechanism from previous observations. PMID:20590327
Arrhythmias and Cardiac Bedside Monitoring in the Neonatal Intensive Care Unit.
McMullen, Sherri L
Cardiac physiology is unique in neonates and infants; there are several physiologic changes that occur in the first weeks of life. Important changes can be captured on the bedside monitor and provide vital data in a noninvasive way to providers. The importance of diligent observation cannot be overstated. Bedside monitoring has improved in the last decade, which has enhanced the ability to detect changes in heart rates and rhythms. The purpose here is to review cardiac physiology, describe those arrhythmias able to be observed on bedside monitors, and highlight heart rate changes that can be early signs of sepsis. PMID:27484664
Challenges of genetic testing in adolescents with cardiac arrhythmia syndromes
Cohen, Lilian Liou; Stolerman, Marina; Walsh, Christine; Wasserman, David; Dolan, Siobhan M
The ability to sequence individual genomes is leading to the identification of an increasing number of genetic risk factors for serious diseases. Knowledge of these risk factors can often provide significant medical and psychological benefit, but also raises complex ethical and social issues. This paper focuses on one area of rapid progress: the identification of mutations causing long QT syndrome and other cardiac channel disorders, which can explain some previously unexplained deaths in infants (SIDS) and children and adults (SUDS) and prevent others from occurring. This genetic knowledge, discovered posthumously in many cases, has implications for clinical care for surviving family members who might carry the same mutations. The information obtained from genetic testing, in the context of personal and family history, can guide individually tailored interventions that reduce risk and save lives. At the same time, obtaining and disclosing genetic information raises difficult issues about confidentiality and decision making within families. We draw on the experience of the Montefiore-Einstein Center for Cardiogenetics, which has played a leading role in the genetic diagnosis and clinical management of cardiac channel diseases, to explore some of the challenging ethical questions arising in affected families with adolescent children. We focus on the related issues of (1) family confidentiality, privacy and disclosure and (2) adolescent decision making about genetic risk, and argue for the value of interdisciplinary dialogue with affected families in resolving these issues. PMID:21955955
Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias.
Dubois, Rémi; Shah, Ashok J; Hocini, Mélèze; Denis, Arnaud; Derval, Nicolas; Cochet, Hubert; Sacher, Frédéric; Bear, Laura; Duchateau, Josselin; Jais, Pierre; Haissaguerre, Michel
Ten years ago, electrocardiographic imaging (ECGI) started to demonstrate its efficiency in clinical settings. The initial application to localize focal ventricular arrhythmias such as ventricular premature beats was probably the easiest to challenge and validates the concept. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff-Parkinson-White syndrome) is described here. PMID:26403066
The pioneering work of George Mines on cardiac arrhythmias: groundbreaking ideas that remain influential in contemporary cardiac electrophysiology.
Aguilar, Martin; Nattel, Stanley
George Mines was a pioneering physiologist who, despite an extremely short period of professional activity and only primitive experimental methodology, succeeded in formulating concepts that continue to be of great influence today. Here, we review some of his most important discoveries and their impact on contemporary concepts and clinical practice. Mines' greatest contribution was his conceptualization and characterization of circus movement reentry. His observations and ideas about the basis for cardiac reentrant activity underlie how we understand and manage a wide range of important clinical rhythm disturbances today. The notions he introduced regarding the influence of premature extrastimuli on reentry (termination, resetting and entrainment) are central to contemporary assessment of arrhythmia mechanisms in clinical electrophysiology laboratories and modern device therapy of cardiac tachyarrhythmias. Refinements of his model of reentry have led to sophisticated biophysical theories of the mechanisms underlying cardiac fibrillation. His seminal observations on the influence of electrolyte derangements and autonomic tone on the heart are relevant to our understanding of the physiology and pharmacology of arrhythmias caused by cardiac pathology. In this era of advanced technology, it is important to appreciate that ideas of lasting impact come from great minds and do not necessarily require great tools. PMID:26607760
Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.
Hong, TingTing; Yang, Huanghe; Zhang, Shan-Shan; Cho, Hee Cheol; Kalashnikova, Mariya; Sun, Baiming; Zhang, Hao; Bhargava, Anamika; Grabe, Michael; Olgin, Jeffrey; Gorelik, Julia; Marbán, Eduardo; Jan, Lily Y; Shaw, Robin M
Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is downregulated in failing hearts. Here we find that cardiac T tubules normally contain dense protective inner membrane folds that are formed by a cardiac isoform of BIN1. In mice with cardiac Bin1 deletion, T-tubule folding is decreased, which does not change overall cardiomyocyte morphology but leads to free diffusion of local extracellular calcium and potassium ions, prolonging action-potential duration and increasing susceptibility to ventricular arrhythmias. We also found that T-tubule inner folds are rescued by expression of the BIN1 isoform BIN1+13+17, which promotes N-WASP-dependent actin polymerization to stabilize the T-tubule membrane at cardiac Z discs. BIN1+13+17 recruits actin to fold the T-tubule membrane, creating a 'fuzzy space' that protectively restricts ion flux. When the amount of the BIN1+13+17 isoform is decreased, as occurs in acquired cardiomyopathy, T-tubule morphology is altered, and arrhythmia can result. PMID:24836577
Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome
Brunner, Michael; Peng, Xuwen; Liu, Gong Xin; Ren, Xiao-Qin; Ziv, Ohad; Choi, Bum-Rak; Mathur, Rajesh; Hajjiri, Mohammed; Odening, Katja E.; Steinberg, Eric; Folco, Eduardo J.; Pringa, Ekatherini; Centracchio, Jason; Macharzina, Roland R.; Donahay, Tammy; Schofield, Lorraine; Rana, Naveed; Kirk, Malcolm; Mitchell, Gary F.; Poppas, Athena; Zehender, Manfred; Koren, Gideon
Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type α subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death. PMID:18464931
Cardiac Spliced BIN1 Folds T-tubule Membrane, Controlling Ion Flux and Limiting Arrhythmia
Hong, TingTing; Yang, Huanghe; Zhang, Shan-Shan; Cho, Hee Cheol; Kalashnikova, Mariya; Sun, Baiming; Zhang, Hao; Bhargava, Anamika; Grabe, Michael; Olgin, Jeffrey; Gorelik, Julia; Marbán, Eduardo; Jan, Lily Y.; Shaw, Robin M.
Cardiomyocyte T-tubules are important for regulating ionic flux. Bridging Integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is down-regulated in failing hearts. Here we find that cardiac T-tubules normally contain dense protective inner membrane folds that are formed by a cardiac spliced isoform of BIN1. In mice with cardiac Bin1 deletion, T-tubule folding is decreased which does not change overall cardiomyocyte morphology, but frees diffusion of local extracellular calcium and potassium ions, prolonging action potential duration, and increasing susceptibility to ventricular arrhythmias. We also find that T-tubule inner folds are rescued only by the BIN1 isoform BIN1+13+17, which promotes N-WASP dependent actin polymerization to stabilize T-tubule membrane at cardiac Z-discs. In conclusion, BIN1+13+17 recruits actin to fold T-tubule membrane, creating a fuzzy space that protectively restricts ionic flux. When BIN1+13+17 is decreased, as occurs in acquired cardiomyopathy, T-tubule morphology is altered and arrhythmias can result. PMID:24836577
Human sinus arrhythmia as an index of vagal cardiac outflow
NASA Technical Reports Server (NTRS)
Eckberg, D. L.
The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.
Automatic recognition of cardiac arrhythmias based on the geometric patterns of Poincaré plots.
Zhang, Lijuan; Guo, Tianci; Xi, Bin; Fan, Yang; Wang, Kun; Bi, Jiacheng; Wang, Ying
The Poincaré plot emerges as an effective tool for assessing cardiovascular autonomic regulation. It displays nonlinear characteristics of heart rate variability (HRV) from electrocardiographic (ECG) recordings and gives a global view of the long range of ECG signals. In the telemedicine or computer-aided diagnosis system, it would offer significant auxiliary information for diagnosis if the patterns of the Poincaré plots can be automatically classified. Therefore, we developed an automatic classification system to distinguish five geometric patterns of the Poincaré plots from four types of cardiac arrhythmias. The statistics features are designed on measurements and an ensemble classifier of three types of neural networks is proposed. Aiming at the difficulty to set a proper threshold for classifying the multiple categories, the threshold selection strategy is analyzed. 24 h ECG monitoring recordings from 674 patients, which have four types of cardiac arrhythmias, are adopted for recognition. For comparison, Support Vector Machine (SVM) classifiers with linear and Gaussian kernels are also applied. The experiment results demonstrate the effectiveness of the extracted features and the better performance of the designed classifier. Our study can be applied to diagnose the corresponding sinus rhythm and arrhythmia substrates disease automatically in the telemedicine and computer-aided diagnosis system. PMID:25582837
Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia
Kim, Hak Ju; Cho, Sungkyu; Kim, Woong-Han
Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D). After CRT-D, left ventricular ejection fraction improved from 22% to 44% assessed by echocardiogram 1 year postoperatively. On electrocardiogram, QRS duration was shortened from 206 to 144 ms. The patient's clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option. PMID:27525239
Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia.
Kim, Hak Ju; Cho, Sungkyu; Kim, Woong-Han
Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D). After CRT-D, left ventricular ejection fraction improved from 22% to 44% assessed by echocardiogram 1 year postoperatively. On electrocardiogram, QRS duration was shortened from 206 to 144 ms. The patient's clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option. PMID:27525239
Contemporary Mapping Techniques of Complex Cardiac Arrhythmias - Identifying and Modifying the Arrhythmogenic Substrate.
Koutalas, Emmanuel; Rolf, Sascha; Dinov, Borislav; Richter, Sergio; Arya, Arash; Bollmann, Andreas; Hindricks, Gerhard; Sommer, Philipp
Cardiac electrophysiology has moved a long way forward during recent decades in the comprehension and treatment of complex cardiac arrhythmias. Contemporary electroanatomical mapping systems, along with state-of-the-art technology in the manufacture of electrophysiology catheters and cardiac imaging modalities, have significantly enriched our armamentarium, enabling the implementation of various mapping strategies and techniques in electrophysiology procedures. Beyond conventional mapping strategies, ablation of complex fractionated electrograms and rotor ablation in atrial fibrillation ablation procedures, the identification and modification of the underlying arrhythmogenic substrate has emerged as a strategy that leads to improved outcomes. Arrhythmogenic substrate modification also has a major role in ventricular tachycardia ablation procedures. Optimisation of contact between tissue and catheter and image integration are a further step forward to augment our precision and effectiveness. Hybridisation of existing technologies with a reasonable cost should be our goal over the next few years. PMID:26835095
Contemporary Mapping Techniques of Complex Cardiac Arrhythmias – Identifying and Modifying the Arrhythmogenic Substrate
Koutalas, Emmanuel; Rolf, Sascha; Dinov, Borislav; Richter, Sergio; Arya, Arash; Bollmann, Andreas; Hindricks, Gerhard
Cardiac electrophysiology has moved a long way forward during recent decades in the comprehension and treatment of complex cardiac arrhythmias. Contemporary electroanatomical mapping systems, along with state-of-the-art technology in the manufacture of electrophysiology catheters and cardiac imaging modalities, have significantly enriched our armamentarium, enabling the implementation of various mapping strategies and techniques in electrophysiology procedures. Beyond conventional mapping strategies, ablation of complex fractionated electrograms and rotor ablation in atrial fibrillation ablation procedures, the identification and modification of the underlying arrhythmogenic substrate has emerged as a strategy that leads to improved outcomes. Arrhythmogenic substrate modification also has a major role in ventricular tachycardia ablation procedures. Optimisation of contact between tissue and catheter and image integration are a further step forward to augment our precision and effectiveness. Hybridisation of existing technologies with a reasonable cost should be our goal over the next few years. PMID:26835095
Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias.
Shenasa, Mohammad; Assadi, Hamid; Heidary, Shahriar; Shenasa, Hossein
Ranolazine is currently approved as an antianginal agent in patients with chronic angina (class IIA). Ranolazine exhibits antiarrhythmic effects that are related to its multichannel blocking effect, predominantly inhibition of late sodium (late INa) current and the rapid potassium rectifier current (IKr), as well as ICa, late ICa, and INa-Ca. It also suppresses the early and delayed after depolarizations. Ranolazine is effective in the suppression of atrial and ventricular arrhythmias (off-label use) without significant proarrhythmic effect. Currently, ongoing trials are evaluating the efficacy and safety of ranolazine in patients with cardiac arrhythmias; preliminary results suggest that ranolazine, when used alone or in combination with dronedarone, is safe and effective in reducing atrial fibrillation. Ranolazine is not currently approved by the US Food and Drug Administration as an antiarrhythmic agent. PMID:27261835
Can we protect from malignant arrhythmias by modulation of cardiac cell-to-cell coupling?
Tribulova, Narcis; Szeiffova Bacova, Barbara; Benova, Tamara; Viczenczova, Csilla
Defects in intercellular coupling in the heart play a key role in the initiation and persistence of malignant arrhythmias. Such disorders result from abnormal expression and distribution of connexins, the major constituents of cardiac gap junction channels. The alterations of myocardial connexin are well established as a consistent feature of both human and animal heart disease and aging. Following these facts, the modulation of connexin mediated intercellular coupling is suggested as a new antiarrhythmic approach. This review provides recent data supporting this concept. It can be challenging for the development of new antiarrhythmic drugs. Moreover, findings point out the implication of some endogenous compounds in protection from life-threatening arrhythmias via preservation of myocardial connexin. PMID:25732099
Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia
Ying, Shaozhen; Cao, Hong; Hu, He; Wang, Xin; Tang, Yanhong; Huang, Congxin
We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7-/- mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff-perfused Alk7-/- hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito carrying channel), was markedly decreased in Alk7-/- hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia. PMID:26882027
[The use of helium-neon laser in drug-resistant cardiac arrhythmias].
Gel'fgat, E B; Abdullaev, R F; Babaev, Z M; Musabekov, S Sh
Out of 85 patients with cardiac arrhythmias in the presence of chronic coronary heart disease, 28 who were resistant to ethacisine and allapinine were included into the study. They had frequent and persistent arrhythmias. The patients were divided into 2 groups: (1) the patients receiving intravenous He-Ne laser therapy in combination with one of the above drugs; (n = 17) and (2) those taking He-Ne laser therapy alone (n = 11). The efficacy of the therapies were controlled by 24-hour monitoring. An antiarrhythmic effect was more frequently observed when He-Ne laser was combined with one of the above drugs than when it was given alone (67.4 and 36.3%, respectively). PMID:1527940
Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice
Heier, Christopher R.; Satta, Rosalba; Lutz, Cathleen; DiDonato, Christine J.
Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Traditionally, SMA has been described as a motor neuron disease; however, there is a growing body of evidence that arrhythmia and/or cardiomyopathy may present in SMA patients at an increased frequency. Here, we ask whether SMA model mice possess such phenotypes. We find SMA mice suffer from severe bradyarrhythmia characterized by progressive heart block and impaired ventricular depolarization. Echocardiography further confirms functional cardiac deficits in SMA mice. Additional investigations show evidence of both sympathetic innervation defects and dilated cardiomyopathy at late stages of disease. Based upon these data, we propose a model in which decreased sympathetic innervation causes autonomic imbalance. Such imbalance would be characterized by a relative increase in the level of vagal tone controlling heart rate, which is consistent with bradyarrhythmia and progressive heart block. Finally, treatment with the histone deacetylase inhibitor trichostatin A, a drug known to benefit phenotypes of SMA model mice, produces prolonged maturation of the SMA heartbeat and an increase in cardiac size. Treated mice maintain measures of motor function throughout extended survival though they ultimately reach death endpoints in association with a progression of bradyarrhythmia. These data represent the novel identification of cardiac arrhythmia as an early and progressive feature of murine SMA while providing several new, quantitative indices of mouse health. Together with clinical cases that report similar symptoms, this reveals a new area of investigation that will be important to address as we move SMA therapeutics towards clinical success. PMID:20693262
Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias
Dhein, Stefan; Seidel, Thomas; Salameh, Aida; Jozwiak, Joanna; Hagen, Anja; Kostelka, Martin; Hindricks, Gerd; Mohr, Friedrich-Wilhelm
Coordinated electrical activation of the heart is essential for the maintenance of a regular cardiac rhythm and effective contractions. Action potentials spread from one cell to the next via gap junction channels. Because of the elongated shape of cardiomyocytes, longitudinal resistivity is lower than transverse resistivity causing electrical anisotropy. Moreover, non-uniformity is created by clustering of gap junction channels at cell poles and by non-excitable structures such as collagenous strands, vessels or fibroblasts. Structural changes in cardiac disease often affect passive electrical properties by increasing non-uniformity and altering anisotropy. This disturbs normal electrical impulse propagation and is, consequently, a substrate for arrhythmia. However, to investigate how these structural changes lead to arrhythmias remains a challenge. One important mechanism, which may both cause and prevent arrhythmia, is the mismatch between current sources and sinks. Propagation of the electrical impulse requires a sufficient source of depolarizing current. In the case of a mismatch, the activated tissue (source) is not able to deliver enough depolarizing current to trigger an action potential in the non-activated tissue (sink). This eventually leads to conduction block. It has been suggested that in this situation a balanced geometrical distribution of gap junctions and reduced gap junction conductance may allow successful propagation. In contrast, source-sink mismatch can prevent spontaneous arrhythmogenic activity in a small number of cells from spreading over the ventricle, especially if gap junction conductance is enhanced. Beside gap junctions, cell geometry and non-cellular structures strongly modulate arrhythmogenic mechanisms. The present review elucidates these and other implications of passive electrical properties for cardiac rhythm and arrhythmogenesis. PMID:25404918
Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk.
Koenig, Xaver; Kovar, Michael; Boehm, Stefan; Sandtner, Walter; Hilber, Karlheinz
Ibogaine, an alkaloid derived from the African shrub Tabernanthe iboga, has shown promising anti-addictive properties in animals. Anecdotal evidence suggests that ibogaine is also anti-addictive in humans. Thus, it alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug, and despite evidence that ibogaine may disturb the rhythm of the heart, this alkaloid is currently used as an anti-addiction drug in alternative medicine. Here, we report that therapeutic concentrations of ibogaine reduce currents through human ether-a-go-go-related gene potassium channels. Thereby, we provide a mechanism by which ibogaine may generate life-threatening cardiac arrhythmias. PMID:22458604
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Treating Arrhythmias in Children
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Family and population strategies for screening and counselling of inherited cardiac arrhythmias.
van Langen, I M; Hofman, N; Tan, H L; Wilde, A A M
Family screening in inherited cardiac arrhythmias has been performed in The Netherlands since 1996, when diagnostic DNA testing in long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) became technically possible. In multidisciplinary outpatient academic clinics, an adjusted protocol for genetic counselling, originally derived from predictive testing in Huntington's disease, is being used. 1110 individuals, including 842 relatives of index patients, were informed about their risks, and most were tested molecularly and/or clinically for carriership of the disease present in their family. Of 345 relatives who were referred for cardiologic follow-up, 189 are being treated, because of an increased risk of life-threatening arrhythmias. Evaluation of the psychological and social consequences of family screening for inherited arrhythmias can be performed by using the adapted criteria of Wilson and Jüngner, i.e., from a point of view of public health. Preliminary results of psychological research show that parents of children at risk for LQTS show high levels of distress. Many other aspects have to be evaluated yet, making final conclusions about the feasibility of family screening difficult, particularly in HCM. Clinical guidelines are urgently needed. Population screening by molecular testing, for instance in athletic preparticipation screening, will become possible in the future and has its own prerequisites for success. PMID:15176433
Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias
Hara, Munetsugu; Takahashi, Tomoyuki; Mitsumasu, Chiaki; Igata, Sachiyo; Takano, Makoto; Minami, Tomoko; Yasukawa, Hideo; Okayama, Satoko; Nakamura, Keiichiro; Okabe, Yasunori; Tanaka, Eiichiro; Takemura, Genzou; Kosai, Ken-ichiro; Yamashita, Yushiro; Matsuishi, Toyojiro
Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure. PMID:26073556
Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias.
Hara, Munetsugu; Takahashi, Tomoyuki; Mitsumasu, Chiaki; Igata, Sachiyo; Takano, Makoto; Minami, Tomoko; Yasukawa, Hideo; Okayama, Satoko; Nakamura, Keiichiro; Okabe, Yasunori; Tanaka, Eiichiro; Takemura, Genzou; Kosai, Ken-ichiro; Yamashita, Yushiro; Matsuishi, Toyojiro
Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure. PMID:26073556
Cardiac arrhythmia and ischaemic events after combination chemotherapy for testicular cancer.
Villani, F; Misrachi, D; Galimberti, M
The aim of the present investigation was to evaluate the type and the incidence of cardiac arrhythmias and ischaemic events in patients suffering from testicular cancer and submitted to combination chemotherapy with cisplatin, bleomycin and vinblastine (PVB) or etoposide (PEB). Forty-seven patients took part in the study; 23 were treated with PVB and 24 with PEB. Holter monitoring was performed in each patient before chemotherapy and on the 1st, 2nd and 5th day of the first cycle of drug administration. The results showed that combination chemotherapy with PVB or PEB was accompanied by the appearance of, or an increase in, the incidence of supraventricular ectopic beats. No significant difference was found between the two groups. No significant conduction disturbances were recorded. These results show that combination chemotherapy with PVB or PEB, at least during the first cycle, has no significant ventricular arrhythmogenic or ischaemic potency in young people with no history of cardiac disease. PMID:7530660
The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation
Schmidt, Constanze; Kisselbach, Jana; Schweizer, Patrick A; Katus, Hugo A; Thomas, Dierk
Atrial fibrillation (AF) is the most frequently encountered sustained cardiac arrhythmia in clinical practice and a major cause of morbidity and mortality. Effective treatment of AF still remains an unmet medical need. Treatment of AF is based on drug therapy and ablative strategies. Antiarrhythmic drug therapy is limited by a relatively high recurrence rate and proarrhythmic side effects. Catheter ablation suppresses paroxysmal AF in the majority of patients without structural heart disease but is more difficult to achieve in patients with persistent AF or with concomitant cardiac disease. Stroke is a potentially devastating complication of AF, requiring anticoagulation that harbors the risk of bleeding. In search of novel treatment modalities, targeted pharmacological treatment and gene therapy offer the potential for greater selectivity than conventional small-molecule or interventional approaches. This paper summarizes the current understanding of molecular mechanisms underlying AF. Established drug therapy and interventional treatment of AF is reviewed, and emerging clinical and experimental therapeutic approaches are highlighted. PMID:21490945
Histone-deacetylase Inhibition Reverses Atrial Arrhythmia Inducibility and Fibrosis in Cardiac Hypertrophy Independent of Angiotensin
Liu, Fang; Levin, Mark D.; Petrenko, Nataliya B.; Lu, Min Min; Wang, Tao; Yuan, Li Jun; Stout, Andrea L.; Epstein, Jonathan A.; Patel, Vickas V.
Atrial fibrosis influences the development of atrial fibrillation (AF), particularly in the setting of structural heart disease where angiotensin-inhibition is partially effective for reducing atrial fibrosis and AF. Histone-deacetylase inhibition reduces cardiac hypertrophy and fibrosis, so we sought to determine if the HDAC inhibitor trichostatin A (TSA) could reduce atrial fibrosis and arrhythmias. Mice over-expressing homeodomain-only protein (HopXTg), which recruits HDAC activity to induce cardiac hypertrophy were investigated in 4 groups (aged 14-18 weeks): wild-type (WT), HopXTg, HopXTg mice treated with TSA for 2 weeks (HopX-TSA) and wild-type mice treated with TSA for 2 weeks (WT-TSA). These groups were characterized using invasive electrophysiology, atrial fibrosis measurements, atrial connexin immunocytochemistry and myocardial angiotensin II measurements. Invasive electrophysiologic stimulation, using the same attempts in each group, induced more atrial arrhythmias in HopXTg mice (48 episodes in 13 of 15 HopXTg mice versus 5 episodes in 2 of 15 HopX-TSA mice, P<0.001; versus 9 episodes in 2 of 15 WT mice, P<0.001; versus no episodes in any WT-TSA mice, P<0.001). TSA reduced atrial arrhythmia duration in HopXTg mice (1307±289 milliseconds versus 148±110 milliseconds, P<0.01) and atrial fibrosis (8.1±1.5% versus 3.9±0.4%, P<0.001). Atrial connexin40 was lower in HopXTg compared to WT mice, and TSA normalized the expression and size distribution of connexin40 gap junctions. Myocardial angiotensin II levels were similar between WT and HopXTg mice (76.3±26.0 versus 69.7±16.6 pg/mg protein, P=NS). Therefore, it appears HDAC inhibition reverses atrial fibrosis, connexin40 remodeling and atrial arrhythmia vulnerability independent of angiotensin II in cardiac hypertrophy. PMID:18926829
LV Dyssynchrony Is Helpful in Predicting Ventricular Arrhythmia in Ischemic Cardiomyopathy After Cardiac Resynchronization Therapy
Tsai, Shih-Chuan; Chang, Yu-Cheng; Chiang, Kuo-Feng; Lin, Wan-Yu; Huang, Jin-Long; Hung, Guang-Uei; Kao, Chia-Hung; Chen, Ji
Abstract For patients with coronary artery disease, larger scar burdens are associated with higher risk of ventricular arrhythmia. Left ventricular (LV) dyssynchrony is associated with increased risk of sudden cardiac death in patients with heart failure. The purpose of this study was to assess the values of LV dyssynchrony and myocardial scar assessed by myocardial perfusion SPECT (MPS) in predicting the development of ventricular arrhythmia in ischemic cardiomyopathy. Twenty-two patients (16 males, mean age: 66 ± 13) with irreversible ischemic cardiomyopathy received cardiac resynchronization therapy (CRT) for at least 12 months were enrolled for MPS. Quantitative parameters, including LV dyssynchrony with phase standard deviation (phase SD) and bandwidth, left ventricular ejection fraction (LVEF), and scar (% of total areas), were generated by Emory Cardiac Toolbox. Ventricular tachycardia (VT) and ventricular fibrillation (VF) recorded in the CRT device during follow-up were used as the reference standard of diagnosing ventricular arrhythmia. Stepwise logistic regression analysis was performed for determining the independent predictors of VT/VF and receiver operating characteristic (ROC) curve analysis was used for generating the optimal cut-off values for predicting VT/VF. Nine (41%) of the 22 patients developed VT/VF during the follow-up periods. Patients with VT/VF had significantly lower LVEF, larger scar, larger phase SD, and larger bandwidth (all P < 0.05). Logistic regression analysis showed LVEF and bandwidth were independent predictors of VT/VF. ROC curve analysis showed the areas under the curves were 0.71 and 0.83 for LVEF and bandwidth, respectively. The optimal cut-off values were <36% and > 139° for LVEF and bandwidth, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 39%, 53%, and 100%, respectively, for LVEF; and were 78%, 92%, 88%, and 86%, respectively, for bandwidth. LV
Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: Mechanisms and model systems.
Pellman, Jason; Zhang, Jing; Sheikh, Farah
Development of cardiac fibrosis and arrhythmias is controlled by the activity of and communication between cardiomyocytes and fibroblasts in the heart. Myocyte-fibroblast interactions occur via both direct and indirect means including paracrine mediators, extracellular matrix interactions, electrical modulators, mechanical junctions, and membrane nanotubes. In the diseased heart, cardiomyocyte and fibroblast ratios and activity, and thus myocyte-fibroblast interactions, change and are thought to contribute to the course of disease including development of fibrosis and arrhythmogenic activity. Fibroblasts have a developing role in modulating cardiomyocyte electrical and hypertrophic activity, however gaps in knowledge regarding these interactions still exist. Research in this field has necessitated the development of unique approaches to isolate and control myocyte-fibroblast interactions. Numerous methods for 2D and 3D co-culture systems have been developed, while a growing part of this field is in the use of better tools for in vivo systems including cardiomyocyte and fibroblast specific Cre mouse lines for cell type specific genetic ablation. This review will focus on (i) mechanisms of myocyte-fibroblast communication and their effects on disease features such as cardiac fibrosis and arrhythmias as well as (ii) methods being used and currently developed in this field. PMID:26996756
A Field Study of the Effects of Traffic Noise on Heart Rate and Cardiac Arrhythmia During Sleep
NASA Astrophysics Data System (ADS)
Carter, N. L.; Ingham, P.; Tran, K.; Hunyor, S. N.
The aim of this study was to test the hypothesis that traffic noise could increase heart rate, and the frequency or severity of cardiac arrhythmias in susceptible people while asleep. Physiological indicators of sleep, electrocardiograph, and respiration and blood oxygen saturation were monitored continuously overnight in seven elderly men living on a busy road. Continuous recordings of the noise outdoors, at the facade, and indoors in the bedrooms, and video recordings of the traffic were made, simultaneously with the physiological measurements. LAeq, LAmax, LApk , LA90, LA10 and LA1 were measured in each 20 s interval, and noise events exceeding 70 dB(A) outdoors and 50 dB(A) indoors for 2 s or longer were logged. Between 03:00 and 05:00 hours, 65% of the traffic consisted of heavy vehicles. With windows open slightly, indoor and outdoor noise exceeded all local, and internationally recommended criteria for adequate sleep by a wide margin. Cardiac arrhythmia occurred during sleep in four of the men. Heart rate and frequency of cardiac arrhythmia were not correlated with indoor LAeq , LApk or LA1, in stage 2, stage 4 and REM sleep. Two of the four subjects with cardiac arrhythmia showed a significant association ( p < 0·05), predominantly in stage 4 sleep, between single indoor noise events and the frequency of cardiac ectopic beats 20-40 s later.
Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.
Partemi, Sara; Vidal, Monica Coll; Striano, Pasquale; Campuzano, Oscar; Allegue, Catarina; Pezzella, Marianna; Elia, Maurizio; Parisi, Pasquale; Belcastro, Vincenzo; Casellato, Susanna; Giordano, Lucio; Mastrangelo, Massimo; Pietrafusa, Nicola; Striano, Salvatore; Zara, Federico; Bianchi, Amedeo; Buti, Daniela; La Neve, Angela; Tassinari, Carlo Alberto; Oliva, Antonio; Brugada, Ramon
Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy. PMID:25119684
CYP2J2 Overexpression Protects against Arrhythmia Susceptibility in Cardiac Hypertrophy
Westphal, Christina; Spallek, Bastian; Konkel, Anne; Marko, Lajos; Qadri, Fatimunnisa; DeGraff, Laura M.; Schubert, Carola; Bradbury, J. Alyce; Regitz-Zagrosek, Vera; Falck, John R.; Zeldin, Darryl C.; Müller, Dominik N.; Schunck, Wolf-Hagen; Fischer, Robert
Maladaptive cardiac hypertrophy predisposes one to arrhythmia and sudden death. Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) promote anti-inflammatory and antiapoptotic mechanisms, and are involved in the regulation of cardiac Ca2+-, K+- and Na+-channels. To test the hypothesis that enhanced cardiac EET biosynthesis counteracts hypertrophy-induced electrical remodeling, male transgenic mice with cardiomyocyte-specific overexpression of the human epoxygenase CYP2J2 (CYP2J2-TG) and wildtype littermates (WT) were subjected to chronic pressure overload (transverse aortic constriction, TAC) or β-adrenergic stimulation (isoproterenol infusion, ISO). TAC caused progressive mortality that was higher in WT (42% over 8 weeks after TAC), compared to CYP2J2-TG mice (6%). In vivo electrophysiological studies, 4 weeks after TAC, revealed high ventricular tachyarrhythmia inducibility in WT (47% of the stimulation protocols), but not in CYP2J2-TG mice (0%). CYP2J2 overexpression also enhanced ventricular refractoriness and protected against TAC-induced QRS prolongation and delocalization of left ventricular connexin-43. ISO for 14 days induced high vulnerability for atrial fibrillation in WT mice (54%) that was reduced in CYP-TG mice (17%). CYP2J2 overexpression also protected against ISO-induced reduction of atrial refractoriness and development of atrial fibrosis. In contrast to these profound effects on electrical remodeling, CYP2J2 overexpression only moderately reduced TAC-induced cardiac hypertrophy and did not affect the hypertrophic response to β-adrenergic stimulation. These results demonstrate that enhanced cardiac EET biosynthesis protects against electrical remodeling, ventricular tachyarrhythmia, and atrial fibrillation susceptibility during maladaptive cardiac hypertrophy. PMID:24023684
Aging is a primary risk factor for cardiac arrhythmias: disruption of intracellular Ca2+ regulation as a key suspect.
Hatch, Fiona; Lancaster, Matthew K; Jones, Sandra A
Aging is an inevitable time-dependent progression associated with a functional decline of the cardiovascular system even in 'healthy' individuals. Age positively correlates with an increasing risk of cardiac problems including arrhythmias. Not only the prevalence but also the severity of arrhythmias escalates with age. The reasons for this are multifactorial but dysregulation of intracellular calcium within the heart is likely to play a key role in initiating and perpetuating these life-threatening events. We now know that several aspects of cardiac calcium regulation significantly change with advancing age - changes that could produce electrical instability. Further development of knowledge of the mechanisms underlying these changes will allow us to reduce what currently is an inevitable increase in the incidence of arrhythmias in the elderly. PMID:21878050
Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature.
Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L Maximilian; Gregoric, Igor D
We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240
Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature
Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L. Maximilian
We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240
KCNE genetics and pharmacogenomics in cardiac arrhythmias: much ado about nothing?
Abbott, Geoffrey W.
Voltage-gated ion channels respond to changes in membrane potential with conformational shifts that either facilitate or stem the movement of charged ions across the cell membrane. This controlled movement of ions is particularly important for the action potentials of excitable cells such as cardiac myocytes, and therefore essential for timely beating of the heart. Inherited mutations in ion channel genes and in the genes encoding proteins that regulate them can cause lethal cardiac arrhythmias either by direct channel disruption or by altering interactions with therapeutic drugs, the best-understood example of both these scenarios being Long QT Syndrome (LQTS). Unsurprisingly, mutations in the genes encoding ion channel pore-forming α subunits underlie the large majority (~90%) of identified cases of inherited LQTS. Given that inherited LQTS is comparatively rare in itself (~0.04% of the US population), is pursuing study of the remaining known and unknown LQTS-associated genes subject to the law of diminishing returns? Here, with a particular focus on the KCNE family of single transmembrane domain K+ channel ancillary subunits, the significance to cardiac pharmacogenetics of ion channel regulatory subunits is discussed. PMID:23272793
Rapidly detecting disorder in rhythmic biological signals: A spectral entropy measure to identify cardiac arrhythmias
NASA Astrophysics Data System (ADS)
Staniczenko, Phillip P. A.; Lee, Chiu Fan; Jones, Nick S.
We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This spectral entropy measure is motivated by characteristic differences in the power spectra of beat timings during the three rhythms. We plot patient data derived from ten-beat windows on a "disorder map" and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classification of periods of atrial fibrillation from the time series of patients' beats. When the algorithm is set to identify abnormal rhythms within 6s , it agrees with 85.7% of the annotations of professional rhythm assessors; for a response time of 30s , this becomes 89.5%, and with 60s , it is 90.3%. The algorithm provides a rapid way to detect atrial fibrillation, demonstrating usable response times as low as 6s . Measures of disorder in the frequency domain have practical significance in a range of biological signals: the techniques described in this paper have potential application for the rapid identification of disorder in other rhythmic signals.
Automatic cardiac arrhythmia detection and classification using vectorcardiograms and complex networks.
Queiroz, Vinícius; Luz, Eduardo; Moreira, Gladston; Guarda, Álvaro; Menotti, David
This paper intends to bring new insights in the methods for extracting features for cardiac arrhythmia detection and classification systems. We explore the possibility for utilizing vectorcardiograms (VCG) along with electrocardiograms (ECG) to get relevant informations from the heartbeats on the MIT-BIH database. For this purpose, we apply complex networks to extract features from the VCG. We follow the ANSI/AAMI EC57:1998 standard, for classifying the beats into 5 classes (N, V, S, F and Q), and de Chazal's scheme for dataset division into training and test set, with 22 folds validation setup for each set. We used the Support Vector Machinhe (SVM) classifier and the best result we chose had a global accuracy of 84.1%, while still obtaining relatively high Sensitivities and Positive Predictive Value and low False Positive Rates, when compared to other papers that follows the same evaluation methodology that we do. PMID:26737464
Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics
Abunimer, Ayman; Smith, Krista; Wu, Tsung-Jung; Lam, Phuc; Simonyan, Vahan; Mazumder, Raja
Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias—a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs) that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to identify additional non-synonymous mutations that affect the proteome, we analyzed the post-translational modification S-nitrosylation, which is known to affect cardiac arrhythmias. We identified loss of seven known S-nitrosylation sites due to non-synonymous single nucleotide variations (nsSNVs). For predicted nitrosylation sites we found 1429 proteins where the sites are modified due to nsSNV. Analysis of the predicted S-nitrosylation dataset for over- or under-representation (compared to the complete human proteome) of pathways and functional elements shows significant statistical over-representation of the blood coagulation pathway. Gene Ontology (GO) analysis displays statistically over-represented terms related to muscle contraction, receptor activity, motor activity, cystoskeleton components, and microtubule activity. Through the genomic and proteomic context of SNVs and S-nitrosylation sites presented in this study, researchers can look for variation that can predispose individuals to cardiac arrhythmias. Such attempts to elucidate mechanisms of arrhythmia thereby add yet another useful parameter in predicting susceptibility for cardiac diseases. PMID:24705329
Inherited arrhythmia syndromes leading to sudden cardiac death in the young: A global update and an Indian perspective
Chockalingam, Priya; Wilde, Arthur A.
Inherited primary arrhythmias, namely congenital long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, account for a significant proportion of sudden cardiac deaths in young and apparently healthy individuals. Genetic testing plays an integral role in the diagnosis, risk-stratification and treatment of probands and family members. It is increasingly obvious that collaborative efforts are required to understand and manage these relatively rare but potentially lethal diseases. This article aims to update readers on the recent developments in our knowledge of inherited arrhythmias and to lay the foundation for a national synergistic effort to characterize them in the Indian population. PMID:24568830
Gating pore currents, a new pathological mechanism underlying cardiac arrhythmias associated with dilated cardiomyopathy
Moreau, Adrien; Gosselin-Badaroudine, Pascal; Chahine, Mohamed
Voltage-gated ion channels (VGIC) are transmembrane proteins responsible for the generation of electrical signals in excitable cells. VGIC were first described in 1952 by Hodgkin and Huxley,1 and have since been associated with various physiological functions such as propagating nerve impulses, locomotion, and cardiac excitability. VGIC include channels specialized in the selective passage of K+, Ca2+ Na+, or H+. They are composed of 2 main structures: the pore domain (PD) and the voltage sensor domain (VSD). The PD ensures the physiological flow of ions and is typically composed of 8 transmembrane segments (TM). The VSD detects voltage variations and is composed of 4 TM (S1-S4). Given their crucial physiological role, VGIC dysfunctions are associated with diverse pathologies known as ion channelopathies. These dysfunctions usually affect the membrane expression of ion channels or voltage-dependent conformational changes of the pore. However, an increasing number of ion channelopathies, including periodic paralysis, dilated cardiomyopathy (DCM) associated with cardiac arrhythmias, and peripheral nerve hyperexcitability (PNH), have been linked to the appearance of a new pathological mechanism involving the creation of an alternative permeation pathway through the normally non-conductive VSD of VGIC. This permeation pathway is called the gating pore or omega pore. PMID:26046592
Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia
Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.
Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341
Disclosing Genetic Information to Family Members About Inherited Cardiac Arrhythmias: An Obligation or a Choice?
Vavolizza, Rick D; Kalia, Isha; Erskine Aaron, Kathleen; Silverstein, Louise B; Barlevy, Dorit; Wasserman, David; Walsh, Christine; Marion, Robert W; Dolan, Siobhan M
Inherited cardiac arrhythmias such as long QT syndrome and Brugada syndrome, present clinical as well as ethical, legal, and social challenges. Many individuals who carry a deleterious mutation are largely asymptomatic and therefore may not be diagnosed until after the occurrence of a personal or family member's cardiac event. The familial nature of inherited genetic information raises numerous ethical, legal, and social issues regarding the sharing of genetic information, particularly when an individual found to carry a deleterious mutation refuses to disclose his or her results to at-risk family members who could benefit from life-saving treatments. This qualitative study sought to understand the experiences with genetic testing for individuals (n = 50) with a personal or family history of cardiac events or sudden death. Unstructured in-person focus groups or interviews were conducted for each participant in the study. The recordings of these interviews were transcribed verbatim and subsequently analyzed and coded. Participants' comments regarding sharing of genetic information centered around four main themes: (1) motivation to disclose; (2) extent of disclosure; (3) effect of disclosure on family dynamics; and (4) reasons for not sharing genetic information. The majority of individuals believed that affected individuals are obligated to disclose genetic information to family members. In the era of personalized medicine, the disclosure of genetic information provides individuals the opportunities to learn about the genetics, disease characteristics, and treatment options in order to reduce morbidity and mortality in themselves and their family members. Further research is necessary to identify and explore the barriers to sharing genetic information with at-risk family members. PMID:25400212
Prolonged Hypoxia Increases Survival Even in Zebrafish (Danio rerio) Showing Cardiac Arrhythmia
Kopp, Renate; Bauer, Ines; Ramalingam, Anil; Egg, Margit; Schwerte, Thorsten
Tolerance towards hypoxia is highly pronounced in zebrafish. In this study even beneficial effects of hypoxia, specifically enhanced survival of zebrafish larvae, could be demonstrated. This effect was actually more pronounced in breakdance mutants, which phenotypically show cardiac arrhythmia. Breakdance mutants (bre) are characterized by chronically reduced cardiac output. Despite an about 50% heart rate reduction, they become adults, but survival rate significantly drops to 40%. Normoxic bre animals demonstrate increased hypoxia inducible factor 1 a (Hif-1α) expression, which indicates an activated hypoxic signaling pathway. Consequently, cardiovascular acclimation, like cardiac hypertrophy and increased erythrocyte concentration, occurs. Thus, it was hypothesized, that under hypoxic conditions survival might be even more reduced. When bre mutants were exposed to hypoxic conditions, they surprisingly showed higher survival rates than under normoxic conditions and even reached wildtype values. In hypoxic wildtype zebrafish, survival yet exceeded normoxic control values. To specify physiological acclimation, cardiovascular and metabolic parameters were measured before hypoxia started (3 dpf), when the first differences in survival rate occurred (7 dpf) and when survival rate plateaued (15 dpf). Hypoxic animals expectedly demonstrated Hif-1α accumulation and consequently enhanced convective oxygen carrying capacity. Moreover, bre animals showed a significantly enhanced heart rate under hypoxic conditions, which reached normoxic wildtype values. This improvement in convective oxygen transport ensured a sufficient oxygen and nutrient supply and was also reflected in the significantly higher mitochondrial activity. The highly optimized energy metabolism observed in hypoxic zebrafish larvae might be decisive for periods of higher energy demand due to organ development, growth and increased activity. However, hypoxia increased survival only during a short period of
Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes
Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano
Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211
Short-Term Exposure to Air Pollution and Cardiac Arrhythmia: A Meta-Analysis and Systematic Review
Song, Xuping; Liu, Yu; Hu, Yuling; Zhao, Xiaoyan; Tian, Jinhui; Ding, Guowu; Wang, Shigong
The objective was to assess the transient association between air pollution and cardiac arrhythmia. Five databases were searched for studies investigating the association between daily increases in air pollutants (PM2.5, PM10, carbon monoxide, nitrogen dioxide, sulfur dioxide and ozone) and arrhythmia hospitalization or arrhythmia mortality. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Outcomes were analyzed via a random-effects model and reported as relative risk and 95% confidence interval. 25 studies satisfied our inclusion criteria and 23 contributed to the meta-analysis. Arrhythmia hospitalization or mortality were associated with increases in PM2.5 (RR = 1.015 per 10 μg/m3, 95% CI: 1.006–1.024), PM10 (RR = 1.009 per 10 μg/m3, 95% CI: 1.004–1.014), carbon monoxide (RR = 1.041 per 1 ppm, 95% CI: 1.017–1.065), nitrogen dioxide (RR = 1.036 per 10 ppb, 95% CI: 1.020–1.053), and sulfur dioxide (RR = 1.021 per 10 ppb, 95% CI: 1.003–1.039), but not ozone (RR = 1.012 per 10 ppb, 95% CI: 0.997–1.027). Both particulate and gaseous components, with the exception of ozone, have a temporal association with arrhythmia hospitalization or mortality. Compared with Europe and North America, a stronger association was noted in Asia. PMID:27367707
Short-Term Exposure to Air Pollution and Cardiac Arrhythmia: A Meta-Analysis and Systematic Review.
Song, Xuping; Liu, Yu; Hu, Yuling; Zhao, Xiaoyan; Tian, Jinhui; Ding, Guowu; Wang, Shigong
The objective was to assess the transient association between air pollution and cardiac arrhythmia. Five databases were searched for studies investigating the association between daily increases in air pollutants (PM2.5, PM10, carbon monoxide, nitrogen dioxide, sulfur dioxide and ozone) and arrhythmia hospitalization or arrhythmia mortality. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Outcomes were analyzed via a random-effects model and reported as relative risk and 95% confidence interval. 25 studies satisfied our inclusion criteria and 23 contributed to the meta-analysis. Arrhythmia hospitalization or mortality were associated with increases in PM2.5 (RR = 1.015 per 10 μg/m³, 95% CI: 1.006-1.024), PM10 (RR = 1.009 per 10 μg/m³, 95% CI: 1.004-1.014), carbon monoxide (RR = 1.041 per 1 ppm, 95% CI: 1.017-1.065), nitrogen dioxide (RR = 1.036 per 10 ppb, 95% CI: 1.020-1.053), and sulfur dioxide (RR = 1.021 per 10 ppb, 95% CI: 1.003-1.039), but not ozone (RR = 1.012 per 10 ppb, 95% CI: 0.997-1.027). Both particulate and gaseous components, with the exception of ozone, have a temporal association with arrhythmia hospitalization or mortality. Compared with Europe and North America, a stronger association was noted in Asia. PMID:27367707
Particles Alter Diesel Exhaust Gases-Induced Hypotension, Cardiac Arrhythmia,Conduction Disturbance, and Autonomic Imbalance in Heart Failure-Prone Rats
Epidemiologic studies indicate that acute exposures to vehicular traffic and particulate matter (PM) air pollution are key causes of fatal cardiac arrhythmia, especially in those with preexisting cardiovascular disease. Researchers point to electrophysiologic dysfunction and auto...
How are arrhythmias detected by implanted cardiac devices managed in Europe? Results of the European Heart Rhythm Association Survey.
Todd, Derick; Hernandez-Madrid, Antonio; Proclemer, Alessandro; Bongiorni, Maria Grazia; Estner, Heidi; Blomström-Lundqvist, Carina
The management of arrhythmias detected by implantable cardiac devices can be challenging. There are no formal international guidelines to inform decision-making. The purpose of this European Heart Rhythm Association (EHRA) survey was to assess the management of various clinical scenarios among members of the EHRA electrophysiology research network. There were 49 responses to the questionnaire. The survey responses were mainly (81%) from medium-high volume device implanting centres, performing more than 200 total device implants per year. Clinical scenarios were described focusing on four key areas: the implantation of pacemakers for bradyarrhythmia detected on an implantable loop recorder (ILR), the management of patients with ventricular arrhythmia detected by an ILR or pacemaker, the management of atrial fibrillation in patients with pacemakers and cardiac resynchronization therapy devices and the management of ventricular tachycardia in patients with implantable cardioverter-defibrillators. PMID:26443791
Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias
NASA Astrophysics Data System (ADS)
Vago, Hajnalka
apply effectively biatrial pacemaker and biatrial cardioverter defibrillator for the prevention of paroxysmal atrial fibrillation. In the majority of patients frequency of paroxysmal atrial fibrillation decreased significantly due to biatrial stimulation or combined pharmacological and resynchronisation therapy. Parasymphathetic cardiac neurostimulation is a promising new non-pharmacological treatment option in certain types of arrhythmias. In our clinical study we were able to stimulate cardiac parasympathetic nerves innervating atrioventricular node achieving ventricular rate control during atrial tachyarrhythmias with chronically implanted coronary sinus lead. In our study biventricular pacemakers and cardioverter defibrillators were applied successfully in the treatment of drug refractory congestive heart failure combined with inter- and/or intraventricular conduction disturbances. AV sequential left sided chronic pacing using a single lead located in the coronary sinus has not been previously reported. Left sided DDD pacing was effective chronically in the improvement of the functional stage of patient suffering from congestive heart disease combined with left bundle branch block and binodal disease. Parallel with the investigation of pathomechanism of life-threatening ventricular tachyarrhythmias and the most common, clinically relevant atrial fibrillation due to recent technical development, we were able to support nonpharmacological therapeutic modalities, gaining popularity in clinical management, with novel observations.
Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.
Gibbons, David D; Southerland, E Marie; Hoover, Donald B; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L
Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential. PMID:22088304
Effect of Continued Cardiac Resynchronization Therapy on Ventricular Arrhythmias After Left Ventricular Assist Device Implantation.
Schleifer, John William; Mookadam, Farouk; Kransdorf, Evan P; Nanda, Udai; Adams, Jonathon C; Cha, Stephen; Pajaro, Octavio E; Steidley, David Eric; Scott, Robert L; Carvajal, Tomas; Saadiq, Rayya A; Srivathsan, Komandoor
Cardiac resynchronization therapy (CRT) reduces ventricular arrhythmia (VA) burden in some patients with heart failure, but its effect after left ventricular assist device (LVAD) implantation is unknown. We compared VA burden in patients with CRT devices in situ who underwent LVAD implantation and continued CRT (n = 39) to those who had CRT turned off before discharge (n = 26). Implantable cardioverter-defibrillator (ICD) shocks were significantly reduced in patients with continued CRT (1.5 ± 2.7 shocks per patient vs 5.5 ± 9.3 with CRT off, p = 0.014). There was a nonsignificant reduction in cumulative VA episodes per patient with CRT continued at discharge (42 ± 105 VA per patient vs 82 ± 198 with CRT off, p = 0.29). On-treatment analysis by whether CRT was on or off identified a significantly lower burden of VA (17 ± 1 per patient-year CRT on vs 37 ± 1 per patient-year CRT off, p <0.0001) and ICD shocks (1.2 ± 0.3 per patient-year CRT on vs 1.7 ± 0.3 per patient-year CRT off, p = 0.018). In conclusion, continued CRT is associated with significantly reduced ICD shocks and VA burden after LVAD implantation. PMID:27328958
Coxsackie and adenovirus receptor (CAR) is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia
Marsman, Roos F.J.; Bezzina, Connie R.; Freiberg, Fabian; Verkerk, Arie O.; Adriaens, Michiel E.; Podliesna, Svitlana; Chen, Chen; Purfürst, Bettina; Spallek, Bastian; Koopmann, Tamara T.; Baczko, Istvan; dos Remedios, Cristobal G.; George, Alfred L.; Bishopric, Nanette H.; Lodder, Elisabeth M.; de Bakker, Jacques M.T.; Fischer, Robert; Coronel, Ruben; Wilde, Arthur A.M.; Gotthardt, Michael; Remme, Carol Ann
Objectives To investigate the modulatory effect of the Coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Background A heritable component in risk for ventricular fibrillation (VF) during myocardial infarction (MI) has been well established. A recent genome-wide association study (GWAS) for VF during acute MI has led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the coxsackie and adenovirus receptor (CAR), a cell adhesion molecule predominantly located at intercalated discs of the cardiomyocyte. Methods The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed CAR haploinsufficient mice (CAR+/−). Results In human left ventricular samples, the risk allele at the chr21q21 GWAS locus was associated with lower CXADR mRNA levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced VF. Hearts from CAR+/− mice displayed ventricular conduction slowing in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia following LAD ligation. Connexin43 expression and distribution was unaffected, but CAR+/− hearts displayed increased arrhythmia susceptibility upon pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR+/− myocytes showed reduced sodium current magnitude specifically at the intercalated disc. Moreover, CAR co-precipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. Conclusion We identify CAR as a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk
Human G109E-inhibitor-1 impairs cardiac function and promotes arrhythmias.
Haghighi, Kobra; Pritchard, Tracy J; Liu, Guan-Sheng; Singh, Vivek P; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G
A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2Hz +/- Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to
Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs.
Herrera, José A; Ward, Christopher S; Pitcher, Meagan R; Percy, Alan K; Skinner, Steven; Kaufmann, Walter E; Glaze, Daniel G; Wehrens, Xander H T; Neul, Jeffrey L
One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na(+) channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na(+) channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na(+) channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na(+) channel blocker antiepileptic therapies. Thus, Na(+) channel blockers should be considered for the clinical management of LQT in individuals with RTT. PMID:25713300
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
Freyermuth, Fernande; Rau, Frédérique; Kokunai, Yosuke; Linke, Thomas; Sellier, Chantal; Nakamori, Masayuki; Kino, Yoshihiro; Arandel, Ludovic; Jollet, Arnaud; Thibault, Christelle; Philipps, Muriel; Vicaire, Serge; Jost, Bernard; Udd, Bjarne; Day, John W; Duboc, Denis; Wahbi, Karim; Matsumura, Tsuyoshi; Fujimura, Harutoshi; Mochizuki, Hideki; Deryckere, François; Kimura, Takashi; Nukina, Nobuyuki; Ishiura, Shoichi; Lacroix, Vincent; Campan-Fournier, Amandine; Navratil, Vincent; Chautard, Emilie; Auboeuf, Didier; Horie, Minoru; Imoto, Keiji; Lee, Kuang-Yung; Swanson, Maurice S; Lopez de Munain, Adolfo; Inada, Shin; Itoh, Hideki; Nakazawa, Kazuo; Ashihara, Takashi; Wang, Eric; Zimmer, Thomas; Furling, Denis; Takahashi, Masanori P; Charlet-Berguerand, Nicolas
Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a reduced excitability compared with the control adult isoform. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy. PMID:27063795
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy
Freyermuth, Fernande; Rau, Frédérique; Kokunai, Yosuke; Linke, Thomas; Sellier, Chantal; Nakamori, Masayuki; Kino, Yoshihiro; Arandel, Ludovic; Jollet, Arnaud; Thibault, Christelle; Philipps, Muriel; Vicaire, Serge; Jost, Bernard; Udd, Bjarne; Day, John W.; Duboc, Denis; Wahbi, Karim; Matsumura, Tsuyoshi; Fujimura, Harutoshi; Mochizuki, Hideki; Deryckere, François; Kimura, Takashi; Nukina, Nobuyuki; Ishiura, Shoichi; Lacroix, Vincent; Campan-Fournier, Amandine; Navratil, Vincent; Chautard, Emilie; Auboeuf, Didier; Horie, Minoru; Imoto, Keiji; Lee, Kuang-Yung; Swanson, Maurice S.; de Munain, Adolfo Lopez; Inada, Shin; Itoh, Hideki; Nakazawa, Kazuo; Ashihara, Takashi; Wang, Eric; Zimmer, Thomas; Furling, Denis; Takahashi, Masanori P.; Charlet-Berguerand, Nicolas
Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a reduced excitability compared with the control adult isoform. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy. PMID:27063795
Short-term forecasting of life-threatening cardiac arrhythmias based on symbolic dynamics and finite-time growth rates
NASA Astrophysics Data System (ADS)
Wessel, Niels; Ziehmann, Christine; Kurths, Jürgen; Meyerfeldt, Udo; Schirdewan, Alexander; Voss, Andreas
Ventricular tachycardia or fibrillation (VT-VF) as fatal cardiac arrhythmias are the main factors triggering sudden cardiac death. The objective of this study is to find early signs of sustained VT-VF in patients with an implanted cardioverter-defibrillator (ICD). These devices are able to safeguard patients by returning their hearts to a normal rhythm via strong defibrillatory shocks; additionally, they store the 1000 beat-to-beat intervals immediately before the onset of a life-threatening arrhythmia. We study these 1000 beat-to-beat intervals of 17 chronic heart failure ICD patients before the onset of a life-threatening arrhythmia and at a control time, i.e., without a VT-VF event. To characterize these rather short data sets, we calculate heart rate variability parameters from the time and frequency domain, from symbolic dynamics as well as the finite-time growth rates. We find that neither the time nor the frequency domain parameters show significant differences between the VT-VF and the control time series. However, two parameters from symbolic dynamics as well as the finite-time growth rates discriminate significantly both groups. These findings could be of importance in algorithms for next generation ICD's to improve the diagnostics and therapy of VT-VF.
ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats.
Farraj, Aimen K; Hazari, Mehdi S; Haykal-Coates, Najwa; Lamb, Christina; Winsett, Darrell W; Ge, Yue; Ledbetter, Allen D; Carll, Alex P; Bruno, Maribel; Ghio, Andy; Costa, Daniel L
Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an important contributor to ambient fine particulate air pollution. We hypothesized that a single-inhalation exposure to transition metal-rich PM will cause concentration-dependent cardiovascular toxicity in spontaneously hypertensive (SH) rats. Rats implanted with telemeters to monitor heart rate and electrocardiogram were exposed once by nose-only inhalation for 4 hours to 3.5 mg/m(3), 1.0 mg/m(3), or 0.45 mg/m(3) of a synthetic PM (dried salt solution), similar in composition to a well-studied ROFA sample consisting of Fe, Ni, and V. Exposure to the highest concentration of PM decreased T-wave amplitude and area, caused ST depression, reduced heart rate (HR), and increased nonconducted P-wave arrhythmias. These changes were accompanied by increased pulmonary inflammation, lung resistance, and vagal tone, as indicated by changes in markers of HR variability (increased root of the mean of squared differences of adjacent RR intervals [RMSSD], low frequency [LF], high frequency [HF], and decreased LF/HF), and attenuated myocardial micro-RNA (RNA segments that suppress translation by targeting messenger RNA) expression. The low and intermediate concentrations of PM had less effect on the inflammatory, HR variability, and micro-RNA endpoints, but still caused significant reductions in HR. In addition, the intermediate concentration caused ST depression and increased QRS area, whereas the low concentration increased the T-wave parameters. Thus, PM-induced cardiac dysfunction is mediated by multiple mechanisms that may be dependent on PM concentration and myocardial vulnerability (this abstract does not reflect the policy of the United States Environmental
Pilot evaluation of an integrated monitor-adhesive patch for long-term cardiac arrhythmia detection in India.
Shrivastav, Maneesh; Padte, Sanjay; Arora, Vanita; Biffi, Mauro
Electrocardiographic monitoring represents one of the most reliable and time-tested methods for reducing ambiguity in cardiac arrhythmia diagnosis. In India, the resting ECG is generally the first tool of choice for in-clinic diagnosis. The external loop recorder (ELR) is another useful tool that compounds the advantages of traditional tools by coupling ambulatory monitoring with a long-term window. Thus, the objective was to test the use of a 7-day ELR for arrhythmia diagnosis in India for a broad range of presenting symptoms. In this study set in the Indian healthcare environment, an auto-triggered, wireless patch-type ELR was used with 125 patients (62.5 ± 16.7 years, 76 males) presenting a broad range of symptoms. Eighty percent of the symptoms were related to syncope, presyncope or palpitations. Patients were administered an ELR for 7-28 days depending on the physician's prescription. Prespecified significant arrhythmias included sinus pause >2 s, symptomatic bradycardia <40 b.p.m., second-degree (and higher) AV block, complete heart block, ventricular fibrillation, sustained/nonsustained ventricular tachycardia (>3 beats), atrial fibrillation (chronic or paroxysmal), atrial flutter and supraventricular tachycardia (SVT) >130 b.p.m. Diagnostic yield was 38% when a stringent tabulation methodology considering only clinically significant arrhythmia was used. When first-degree AV block, premature atrial and ventricular beats, couplets (both atrial and ventricular in origin), bigeminy or trigeminy, or sudden changes in rate (noted as sinus arrhythmia) were included in the calculation, diagnostic yield was 80%. Patient compliance was 98%; patients wore the patch for the entire prescribed monitoring period without disruption. Seventy percent of the reported symptoms corresponded with an arrhythmia. Use of the ELR led to therapy change in 24% of patients: 15 patients went on to receive an implantable cardioverter defibrillator or pacemaker, 4 received ablation
Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy
Saragoca, M.A.; Canziani, M.E.; Gil, M.A.; Castiglioni, M.L.; Cassiolato, J.L.; Barbieri, A.; Lima, V.C.; Draibe, S.A.; Martinez, E.E. )
In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program.
Lewalter, Thorsten; Koutsouraki, Ilia; Brodherr, Turgut
Intermittent cardiac arrhythmias are sometimes difficult to register using conventional detection concepts. The implantable event recorders offer a unique opportunity to document short lasting or rare and even asymptomatic arrhythmias. This manuscript describes event recorder implantation in a step-by-step manner. PMID:26306017
Cardiac arrhythmia is the primary response of embryonic Pacific herring (Clupea pallasi) exposed to crude oil during weathering.
Incardona, John P; Carls, Mark G; Day, Heather L; Sloan, Catherine A; Bolton, Jennie L; Collier, Tracy K; Scholz, Nathaniel L
Teleost embryos develop a syndrome characterized by edema when exposed to water that weathers substrates contaminated with crude oil. Previous studies using zebrafish demonstrated that crude oil exposure causes cardiogenic edema, and that the most abundant polycyclic aromatic hydrocarbons (PAHs) in weathered crude oils (tricyclic fluorenes, dibenzothiophenes, and phenanthrenes) are cardiotoxic, causing arrhythmia through a pathway that does not require activation of the aryl hydrocarbon receptor (AHR). We demonstrate here for Pacific herring, a species impacted by the Exxon Valdez oil spill, that the developing heart is the primary target of crude oil exposure. Herring embryos exposed to the effluent of oiled gravel columns developed dose-dependent edema and irregular cardiac arrhythmia soon afterthe heartbeat was established. At a dose that produced cardiac dysfunction in 100% of exposed embryos, tissue levels of tricyclic PAHs were below 1 micromol/kg, suggesting a specific, high affinity target in the heart. These findings have implications for understanding the mechanism of tricyclic PAH cardiotoxicity, the development of biomarkers for the effects of PAH exposure in fish, and understanding the long-term impacts of oil spills and other sources of PAH pollution in aquatic environments. PMID:19209607
Next-generation sequencing for the diagnosis of cardiac arrhythmia syndromes.
Lubitz, Steven A; Ellinor, Patrick T
Inherited arrhythmia syndromes are collectively associated with substantial morbidity, yet our understanding of the genetic architecture of these conditions remains limited. Recent technological advances in DNA sequencing have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next-generation sequencing allows the large-scale and rapid assessment of entire genomes. Although next-generation sequencing represents a major technological advance, it has introduced numerous challenges with respect to the interpretation of genetic variation and has opened a veritable floodgate of biological data of unknown clinical significance to practitioners. In this review, we discuss current genetic testing indications for inherited arrhythmia syndromes, broadly outline characteristics of next-generation sequencing techniques, and highlight challenges associated with such testing. We further summarize future directions that will be necessary to address to enable the widespread adoption of next-generation sequencing in the routine management of patients with inherited arrhythmia syndromes. PMID:25625719
Inhibition of Thromboxane A2-Induced Arrhythmias and Intracellular Calcium Changes in Cardiac Myocytes by Blockade of the Inositol Trisphosphate Pathway
Kosloski, L. M.; Gilbert, W. J. R.; Touchberry, C. D.; Moore, D. S.; Kelly, J. K.; Brotto, M.; Orr, J. A.
We have recently reported that left atrial injections of the thromboxane A2 (TXA2) mimetic, (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 -oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), induced ventricular arrhythmias in the anesthetized rabbit. Data from this study led us to hypothesize that TXA2 may be inducing direct actions on the myocardium to induce these arrhythmias. The aim of this study was to further elucidate the mechanism responsible for these arrhythmias. We report that TXA2R is expressed at both the gene and protein levels in atrial and ventricular samples of adult rabbits. In addition, TXA2R mRNA was identified in single, isolated ventricular cardiac myocytes. Furthermore, treatment of isolated cardiac myocytes with U46619 increased intracellular calcium in a dose-dependent manner and these increases were blocked by the specific TXA2R antagonist, 7-(3-((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid (SQ29548). Pretreatment of myocytes with an inhibitor of inositol trisphosphate (IP3) formation, gentamicin, or with an inhibitor of IP3 receptors, 2-aminoethoxydiphenylborate (2-APB), blocked the increase in intracellular calcium. In vivo pretreatment of anesthetized rabbits with either gentamicin or 2-APB subsequently inhibited the formation of ventricular arrhythmias elicited by U46619. These data support the hypothesis that TXA2 can induce arrhythmias via a direct action on cardiac myocytes. Furthermore, these arrhythmogenic actions were blocked by inhibitors of the IP3 pathway. In summary, this study provides novel evidence for direct TXA2-induced cardiac arrhythmias and provides a rationale for IP3 as a potential target for the treatment of TXA2-mediated arrhythmias. PMID:19741149
Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance
Here we describe how air pollution causes cardiac arrhythmogenesis through sensory irritation in the airways. Time-series studies show the risk of adverse cardiac events increases significantly in the hours to days after expos...
Oxidative Stress Induced Ventricular Arrhythmia and Impairment of Cardiac Function in Nos1ap Deleted Mice.
Sugiyama, Koji; Sasano, Tetsuo; Kurokawa, Junko; Takahashi, Kentaro; Okamura, Tadashi; Kato, Norihiro; Isobe, Mitsuaki; Furukawa, Tetsushi
Genome-wide association study has identified that the genetic variations at NOS1AP (neuronal nitric oxide synthase-1 adaptor protein) were associated with QT interval and sudden cardiac death (SCD). However, the mechanism linking a genetic variant of NOS1AP and SCD is poorly understood. We used Nos1ap knockout mice (Nos1ap(-/-)) to determine the involvement of Nos1ap in SCD, paying special attention to oxidative stress.At baseline, a surface electrocardiogram (ECG) and ultrasound echocardiography (UCG) showed no difference between Nos1ap(-/-) and wild-type (WT) mice. Oxidative stress was induced by a single injection of doxorubicin (Dox, 25 mg/kg). After Dox injection, Nos1ap(-/-) showed significantly higher mortality than WT (93.3 versus 16.0% at day 14, P < 0.01). ECG showed significantly longer QTc in Nos1ap(-/-) than WT, and UCG revealed significant reduction of fractional shortening (%FS) only in Nos1ap(-/-) after Dox injection. Spontaneous ventricular tachyarrhythmias were documented by telemetry recording after Dox injection only in Nos1ap(-/-). Ex vivo optical mapping revealed that the action potential duration (APD)90 was prolonged at baseline in Nos1ap(-/-), and administration of Dox lengthened APD90 more in Nos1ap(-/-) than in WT. The expression of Bnp and the H2O2 level were higher in Nos1ap(-/-) after Dox injection. Nos1ap(-/-) showed a reduced amplitude of calcium transient in isolated cardiomyocytes after Dox injection. Administration of the antioxidant N-acetyl-L-cysteine significantly reduced mortality of Nos1ap(-/-) by Dox injection, accompanied by prevention of QT prolongation and a reduction in %FS.Although Nos1ap(-/-) mice have apparently normal hearts, oxidative stress evokes ventricular tachyarrhythmia and heart failure, which may cause sudden cardiac death. PMID:27170476
Influence of electromagnetic interference on implanted cardiac arrhythmia devices in and around a magnetically levitated linear motor car.
Fukuta, Motoyuki; Mizutani, Noboru; Waseda, Katsuhisa
This study was designed to determine the susceptibility of implanted cardiac arrhythmia devices to electromagnetic interference in and around a magnetically levitated linear motor car [High-Speed Surface Transport (HSST)]. During the study, cardiac devices were connected to a phantom model that had similar characteristics to the human body. Three pacemakers from three manufacturers and one implantable cardioverter-defibrillator (ICD) were evaluated in and around the magnetically levitated vehicle. The system is based on a normal conductive system levitated by the attractive force of magnets and propelled by a linear induction motor without wheels. The magnetic field strength at 40 cm from the vehicle in the nonlevitating state was 0.12 mT and that during levitation was 0.20 mT. The magnetic and electric field strengths on a seat close to the variable voltage/variable frequency inverter while the vehicle was moving and at rest were 0.13 mT, 2.95 V/m and 0.04 mT, 0.36 V/m, respectively. Data recorded on a seat close to the reactor while the vehicle was moving and at rest were 0.09 mT, 2.45 V/m and 0.05 mT, 1.46 V/m, respectively. Measured magnetic and electric field strengths both inside and outside the linear motor car were too low to result in device inactivation. No sensing, pacing, or arrhythmic interactions were noted with any pacemaker or ICD programmed in either bipolar and unipolar configurations. In conclusion, our data suggest that a permanent programming change or a device failure is unlikely to occur and that the linear motor car system is probably safe for patients with one of the four implanted cardiac arrhythmia devices used in this study under the conditions tested. PMID:16235032
Geophysical variables and behavior: CIII. Days with sudden infant deaths and cardiac arrhythmias in adults share a factor with PC1 geomagnetic pulsations: implications for pursuing mechanism.
Persinger, M A; O'Connor, R P
If geomagnetic-mediated stimuli trigger many sudden infant deaths, then the days in which they and hospital admissions for cardiac arrhythmias for adults occur should share a similar source of variance. Factor analyses of the days in which a sudden infant death occurred in Ontario or adults were admitted for one of eight categories of cardiac crisis in the Sudbury (Ontario) Region for the year 1984 supported the hypothesis. This factor, with which infant deaths and adult cardiac arrhythmias each shared about 40% of their variance, also shared about 40% of the variance with a factor with which about 35% of the variance in daily occurrence of geomagnetic pulsations (0.2 Hz to 5 Hz) was associated. These results are consistent with the important role of geomagnetic variables in the occurrence of transient electrical anomalies in brain function rather than cardiac blood flow. PMID:11453188
The effects of B0, B20 and B100 soy biodiesel exhaust on aconitine-induced cardiac arrhythmia in spontaneously hypertensive rats
CONTEXT: Diesel exhaust (DE) has been shown to increase the risk of cardiac arrhythmias. Although biodiesel has been proposed as a "safer" alternative to diesel, it is still uncertain whether it actually poses less threat.OBJECTIVE: We hypothesized that exposure to pure...
Assessment of Cardiac Rate and Rhythm in Fetuses with Arrhythmia via Maternal Abdominal Fetal Electrocardiography
Narayan, Hari K.; Vignola, Emilia F.; Fifer, William P.; Williams, Ismee A.
Objective This study aims to report our experience using the Monica AN24 (Monica Healthcare Ltd., Nottingham, United Kingdom), a maternal transabdominal fetal electrocardiographic monitor, in a case series of fetuses with arrhythmias. Study Design We recorded fetal electrocardiograms (fECGs) on subjects with fetal arrhythmias diagnosed by fetal echocardiogram. Fetal heart rate and rhythm were determined via manual fECG analysis. Results Overall, 20 fECGs were recorded from a pool of 13 subjects. Fetal heart rate acquisition was determined to be high, medium, and poor quality in 10, 3, and 7 tracings, respectively. High-quality tracings were obtained in 9 of 11 subjects with gestational age < 26 or > 34 weeks. P waves were detectable in five tracings. Conclusion In subjects < 26 or > 34 weeks' gestational age, there was reasonable success in fetal heart rate acquisition. Further study is warranted to determine the potential role of this device in the monitoring of subjects with fetal arrhythmias. PMID:26495180
Cardiac arrhythmia induced by genetic silencing of "funny" (f) channels is rescued by GIRK4 inactivation
Mesirca, Pietro; Alig, Jacqueline; Torrente, Angelo G.; Müller, Jana Christina; Marger, Laurine; Rollin, Anne; Marquilly, Claire; Vincent, Anne; Dubel, Stefan; Bidaud, Isabelle; Fernandez, Anne; Seniuk, Anika; Engeland, Birgit; Singh, Jasmin; Miquerol, Lucile; Ehmke, Heimo; Eschenhagen, Thomas; Nargeot, Joel; Wickman, Kevin; Isbrandt, Dirk; Mangoni, Matteo E.
The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the "funny" current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca2+]i release and Ca2+ handling in the sinoatrial node, impaired pacemaker activity, and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. PMID:25144323
Incidence and Factors Predicting Skin Burns at the Site of Indifferent Electrode during Radiofrequency Catheter Ablation of Cardiac Arrhythmias
Ibrahim, Hussain; Finta, Bohuslav; Rind, Jubran
Radiofrequency catheter ablation (RFA) has become a mainstay for treatment of cardiac arrhythmias. Skin burns at the site of an indifferent electrode patch have been a rare, serious, and likely an underreported complication of RFA. The purpose of this study was to determine the incidence of skin burns in cardiac RFA procedures performed at one institution. Also, we wanted to determine the factors predicting skin burns after cardiac RFA procedures at the indifferent electrode skin pad site. Methods. A retrospective case control study was performed to compare the characteristics in patients who developed skin burns in a 2-year period. Results. Incidence of significant skin burns after RFA was 0.28% (6/2167). Four of the six patients were female and all were Caucasians. Four controls for every case were age and sex matched. Burn patients had significantly higher BMI, procedure time, and postprocedure pain, relative to control subjects (p < 0.05, one-tailed testing). No one in either group had evidence of dispersive pad malattachment. Conclusions. Our results indicate that burn patients had higher BMI and longer procedure times compared to control subjects. These findings warrant further larger studies on this topic. PMID:27213077
Effect of early bisoprolol administration on ventricular arrhythmia and cardiac death in patients with non-ST elevation myocardial infarction
Maclean, Edd; Zheng, Sean; Nabeebaccus, Adam; O'Gallagher, Kevin; Stewart, Adrian; Webb, Ian
Objective To investigate the impact of early oral beta blockade in patients presenting with acute non-ST elevation myocardial infarction (NSTEMI). Methods We retrospectively identified 890 consecutive patients presenting with NSTEMI to a single UK centre from 2012 to 2014. Included patients all received standardised antiplatelet therapy plus low-dose oral bisoprolol (1.25–2.5 mg) within 4 h (mean 2.2±1.36; 'Early Group') or within 5–24 h (mean 15.4±5.7; 'Late Group') of presentation. Patients were followed up for the duration of hospital stay with the incidence of major adverse cardiovascular events (MACE—defined as ventricular arrhythmia, cardiac death or repeat infarction) set as the primary outcome. Multivariate logistic regression models analysed early versus late bisoprolol administration and adjusted for potential confounders. Results 399 patients were included. Of the patient parameters, only the GRACE score was significantly different between the early (n=99, GRACE 164.5±29.6) and late (n=300, GRACE 156.7±31.4) groups (p=0.033). The early group had significantly fewer ventricular arrhythmias (1 vs 20, p=0.034), cardiac deaths (0 vs 13, p=0.044) and consequently MACE (1 vs 27, p=0.005) than the late group. After adjusting for the confounders of pulse, blood pressure, smoking and creatinine, logistic regression analysis identified early bisoprolol administration as protective for ventricular arrhythmia (p=0.038, OR 0.114, CI 0.015 to 0.885) and MACE (p=0.011, OR 0.064, CI 0.008 to 0.527). There was one episode of symptomatic bradycardia in the late group. Conclusions This study suggests that low-dose oral bisoprolol administered to patients with NSTEMI within 4 h of admission may be protective and lead to reduced inpatient MACE. PMID:27326220
Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects
Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin
Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865
Cardiac glycosides and the risk of breast cancer in women with chronic heart failure and supraventricular arrhythmia.
Couraud, Sébastien; Dell'Aniello, Sophie; Bouganim, Nathaniel; Azoulay, Laurent
The aim of this study is to determine whether the use of cardiac glycosides (CGs), drugs used in the treatment of congestive heart failure (CHF) and supra-ventricular arrhythmia, is associated with an increased risk of breast cancer. A cohort of 53,454 women newly diagnosed with CHF or supra-ventricular arrhythmia between January 1, 1988 and December 31, 2010, followed until December 31, 2012, was identified using the United Kingdom Clinical Practice Research Datalink. A nested case-control analysis was performed, where all incident cases of breast cancer occurring during follow-up were identified and matched with up to 10 controls on age, cohort entry date, and duration of follow-up. Conditional logistic regression models were used to estimate adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) of incident breast cancer associated with the use of CGs, along with measures of cumulative duration of use and dose. All analyses considered a one year lag period prior to the event, necessary for latency considerations and to minimize detection bias. The 898 breast cancer cases diagnosed beyond one year of follow-up were matched to 8,940 controls. Overall, use of CGs was not associated with an increased risk of breast cancer when compared to non-use (OR 1.07, 95 % CI 0.90-1.26). Furthermore, the risk did not vary with cumulative duration of use or cumulative dose. The findings of this large population-based study indicate that the use of CGs is not associated with an increased risk of breast cancer. This should provide reassurance to physicians and patients using these drugs. PMID:25038879
Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
Inherited Cardiac Arrythmias; Long QT Syndrome (LQTS); Brugada Syndrome (BrS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Hypertrophic Cardiomyopathy (HCM); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects
Yang, Kai-Chien; Bonini, Marcelo G.; Dudley, Samuel C.
Mitochondria are essential to providing ATP thereby satisfying the energy demand of the incessant electrical activity and contractile action of cardiac muscle. Emerging evidence indicates that mitochondrial dysfunction can adversely impact cardiac electrical functioning by impairing the intracellular ion homeostasis and membrane excitability through reduced ATP production and excessive reactive oxidative species (ROS) generation, resulting in increased propensity to cardiac arrhythmias. In this review, the molecular mechanisms linking mitochondrial dysfunction to cardiac arrhythmias are discussed with an emphasis on the impact of increased mitochondrial ROS on the cardiac ion channels and transporters that are critical to maintaining normal electromechanical functioning of the cardiomyocytes. The potential of using mitochondria-targeted antioxidants as a novel anti-arrhythmia therapy is highlighted. PMID:24713422
Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart.
Yu, X C; Wu, S; Wang, G Y; Shan, J; Wong, T M; Chen, C F; Pang, K T
The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 microM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia. PMID:11432452
Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers.
Ferrari, Antonio; Compagnoni, Anna; Nandeuil, Anne; Maison-Blanche, Pierre
Chronic obstructive pulmonary disease (COPD) is a multicomponent condition characterized by airway inflammation and associated to comorbidities, including cardiovascular diseases. Among anti-inflammatory agents in development for COPD, the phosphodiesterase inhibitors administrated by inhalation have the potential for increased efficacy and reduced systemic side effects. CHF6001 is an inhaled PDE4 inhibitor with proven anti-inflammatory properties in animal models. This randomized, double-blind, placebo-controlled study was aimed to demonstrate its cardiovascular safety and tolerability in healthy male volunteers with normal electrocardiogram and cardiac parameters. Single and multiple ascending doses (7 days of administration) of CHF6001 were administered. Three electrocardiograms were recorded at several pharmacokinetic time points and at each time points, postdose heart rate, QRS and PR intervals, and presence of arrhythmia were evaluated. In single ascending dose, QTcF intervals did not increase more than 30 milliseconds from the baseline, all heart rate was between 45 and 100 bpm, and no statistically significant differences were observed in PR and QRS intervals. In multiple ascending dose, cardiac parameters did not differ significantly from baseline. In the pharmacokinetic/pharmacodynamic analysis, no medically or clinically significant changes were found. Further studies are ongoing to demonstrate that CHF6001 is safe and well tolerated in COPD patients as well. PMID:26945156
Biological therapies for cardiac arrhythmias: can genes and cells replace drugs and devices?
Cho, Hee Cheol; Marbán, Eduardo
Cardiac rhythm disorders reflect failures of impulse generation and/or conduction. With the exception of ablation methods that yield selective endocardial destruction, present therapies are nonspecific and/or palliative. Progress in understanding the underlying biology opens up prospects for new alternatives. This article reviews the present state of the art in gene- and cell-based therapies to correct cardiac rhythm disturbances. We begin with the rationale for such approaches, briefly discuss efforts to address aspects of tachyarrhythmia, and review advances in creating a biological pacemaker to cure bradyarrhythmia. Insights gained bring the field closer to a paradigm shift away from devices and drugs, and toward biologics, in the treatment of rhythm disorders. PMID:20203316
Effects of Osmotic Stress on the Probability of Stretch-Induced Cardiac Arrhythmias
NASA Astrophysics Data System (ADS)
Parker, Kk; Taylor, Lk; Wray, Cj; Wikswo, Jp; Hansen, De
Ion channels within the plasma membrane of ventricular myocardial cells may relieve cytoskeletal and membrane mechanical stresses. Volume control channels modulate intracellular volume. Stretch-activated channels have a critical role in the initiation of stretch-induced arrhythmias (SIA) and may provide an additional pathway for Ca++ influx that modulates contractility. We tested the hypothesis that the mechanisms by which these two types of channels sense mechanical stresses are similiar. We studied the arrhythmogenic effects of mechanical stretch in six Langendorff-perfused rabbit hearts in which we altered osmotic pressure across the cell membranes. In diastole, the volume was transiently increased in a left ventricular intracavitary fluid- filled ballon, which was connected to a computer-controlled piston pump. Epicardial monophasic action potential recordings showed a marked decrease in the probability of SIA during hypotonic conditions (cells swollen) (from P=0.51 to P=0.06,p=0.009), and contractility (max systolic pressure) decreased (from 51.1 to 19.6 mmHg, p=0.007). Upon return to the isotonic condition, the probability of SIA returned to baseline condition. One explanation for these findings is that stress relaxation of the viscoelastic cytoskeleton during sustained osmotic loading reduces arrhythmogenic effects of elastic loading produced by transient diastolic stretch.
Is respiratory sinus arrhythmia a good index of cardiac vagal tone in exercise?
Casadei, B; Moon, J; Johnston, J; Caiazza, A; Sleight, P
To assess the relative roles of neural and nonneural mechanisms in respiratory sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21 +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan camsylate (3-5 mg/min i.v.). GB was confirmed by the abolition of the reflex bradycardia in response to intravenous phenylephrine and of the blood pressure rise with the cold pressor test. RSA was calculated from the power of the spectral component of the R-R interval variability centered at the breathing frequency. GB decreased but did not abolish RSA. At rest, this nonneural component of RSA was negligible, accounting for < 1% of the control RSA. During GB, exercise did not affect RSA significantly. However, because control RSA was decreased by exercise, the proportion of nonneural RSA increased by 32% (range from 17 to 75%). These results indicate that as the vagal tone decreases with exercise, an increasing proportion of RSA is due to nonneural mechanisms. PMID:8872618
Mosaic Deficiency in Mitochondrial Oxidative Metabolism Promotes Cardiac Arrhythmia during Aging.
Baris, Olivier R; Ederer, Stefan; Neuhaus, Johannes F G; von Kleist-Retzow, Jürgen-Christoph; Wunderlich, Claudia M; Pal, Martin; Wunderlich, F Thomas; Peeva, Viktoriya; Zsurka, Gabor; Kunz, Wolfram S; Hickethier, Tilman; Bunck, Alexander C; Stöckigt, Florian; Schrickel, Jan W; Wiesner, Rudolf J
Aging is a progressive decline of body function, during which many tissues accumulate few cells with high levels of deleted mitochondrial DNA (mtDNA), leading to a defect of mitochondrial functions. Whether this mosaic mitochondrial deficiency contributes to organ dysfunction is unknown. To investigate this, we generated mice with an accelerated accumulation of mtDNA deletions in the myocardium, by expressing a dominant-negative mutant mitochondrial helicase. These animals accumulated few randomly distributed cardiomyocytes with compromised mitochondrial function, which led to spontaneous ventricular premature contractions and AV blocks at 18 months. These symptoms were not caused by a general mitochondrial dysfunction in the entire myocardium, and were not observed in mice at 12 months with significantly lower numbers of dysfunctional cells. Therefore, our results suggest that the disposition to arrhythmia typically found in the aged human heart might be due to the random accumulation of mtDNA deletions and the subsequent mosaic respiratory chain deficiency. PMID:25955204
Cardiac Arrhythmias Classification Method Based on MUSIC, Morphological Descriptors, and Neural Network
NASA Astrophysics Data System (ADS)
Naghsh-Nilchi, Ahmad R.; Kadkhodamohammadi, A. Rahim
An electrocardiogram (ECG) beat classification scheme based on multiple signal classification (MUSIC) algorithm, morphological descriptors, and neural networks is proposed for discriminating nine ECG beat types. These are normal, fusion of ventricular and normal, fusion of paced and normal, left bundle branch block, right bundle branch block, premature ventricular concentration, atrial premature contraction, paced beat, and ventricular flutter. ECG signal samples from MIT-BIH arrhythmia database are used to evaluate the scheme. MUSIC algorithm is used to calculate pseudospectrum of ECG signals. The low-frequency samples are picked to have the most valuable heartbeat information. These samples along with two morphological descriptors, which deliver the characteristics and features of all parts of the heart, form an input feature vector. This vector is used for the initial training of a classifier neural network. The neural network is designed to have nine sample outputs which constitute the nine beat types. Two neural network schemes, namely multilayered perceptron (MLP) neural network and a probabilistic neural network (PNN), are employed. The experimental results achieved a promising accuracy of 99.03% for classifying the beat types using MLP neural network. In addition, our scheme recognizes NORMAL class with 100% accuracy and never misclassifies any other classes as NORMAL.
Complexity-Measure-Based Sequential Hypothesis Testing for Real-Time Detection of Lethal Cardiac Arrhythmias
NASA Astrophysics Data System (ADS)
Chen, Szi-Wen
A novel approach that employs a complexity-based sequential hypothesis testing (SHT) technique for real-time detection of ventricular fibrillation (VF) and ventricular tachycardia (VT) is presented. A dataset consisting of a number of VF and VT electrocardiogram (ECG) recordings drawn from the MIT-BIH database was adopted for such an analysis. It was split into two smaller datasets for algorithm training and testing, respectively. Each ECG recording was measured in a 10-second interval. For each recording, a number of overlapping windowed ECG data segments were obtained by shifting a 5-second window by a step of 1 second. During the windowing process, the complexity measure (CM) value was calculated for each windowed segment and the task of pattern recognition was then sequentially performed by the SHT procedure. A preliminary test conducted using the database produced optimal overall predictive accuracy of[InlineEquation not available: see fulltext.]. The algorithm was also implemented on a commercial embedded DSP controller, permitting a hardware realization of real-time ventricular arrhythmia detection.
Use of an Implantable Loop Recorder in a Chimpanzee (Pan troglodytes) to Monitor Cardiac Arrhythmias and Assess the Effects of Acupuncture and Laser Therapy.
Magden, Elizabeth R; Sleeper, Meg M; Buchl, Stephanie J; Jones, Rebekah A; Thiele, Erica J; Wilkerson, Gregory K
Cardiovascular disease is a leading cause of death in captive chimpanzees and is often associated with myocardial fibrosis, which increases the risk of cardiac arrhythmias. In this case report, we present a 36-y-old male chimpanzee (Pan troglodytes) diagnosed with frequent ventricular premature complexes (VPC). We placed a subcutaneous implantable loop recorder for continual ECG monitoring to assess his arrhythmias without the confounding effects of anesthetics. During his initial treatment with the antiarrhythmia medication amiodarone, he developed thrombocytopenia, and the drug was discontinued. After reviewing other potential therapies for the treatment of cardiac arrhythmias, we elected to try acupuncture and laser therapy in view of the positive results and the lack of adverse side effects reported in humans. We used 2 well-known cardiac acupuncture sites on the wrist, PC6 (pericardium 6) and HT7 (heart 7), and evaluated the results of the therapy by using the ECG recordings from the implantable loop recorder. Although periodic increases in the animal's excitement level introduced confounding variables that caused some variation in the data, acupuncture and laser therapy appeared to decrease the mean number of VPC/min in this chimpanzee. PMID:26884410
Effects of Acupuncture at the Yintang and the Chengjiang Acupoints on Cardiac Arrhythmias and Neurocardiogenic Syncope in Emergency First Aid.
Fabrin, Saulo; Soares, Nayara; Pezarezi Yoshimura, Daiana; Hallak Regalo, Simone Cecilio; Donizetti Verri, Edson; de Freitas Vianna, Jacqueline Rodrigues; Gatti Regueiro, Eloisa Maria; Torres da Silva, Josie Resende
This study evaluated the effectiveness of YinTang and ChengJiang acupoints on patients with cardiac arrhythmia and neurocardiogenic syncope in emergency first aid. A 45 year old woman underwent acupuncture. She had a previous history of a valvuloplasty for rheumatic disease and two acute myocardial infarctions, followed by four catheterizations and an angioplasty. Needling of the YinTang acupoint and stimulation of the ChengJiang acupoint through acupressure were performed for 20 minutes soon after syncope and during tachycardia, hypertension, tachypnea, and precordial pain, without any effect on peripheral oxygen saturation (SpO2) or the glycemic index. Data were analyzed comparatively by using the following parameters at rest, during syncope, and at 1 minute and 10 minutes after an emergency acupuncture procedure: blood pressure; heart rate; SpO2; and respiratory rate. We found that acupuncture at YinTang and ChenJiang acupoints induced cardiovascular responses, increased the limits of the body's homeostasis, and normalized the patient's condition in the case of syncope. Acupuncture using a combination of ChengJiang and YinTang acupoints had an immediate effect on the autonomic nervous system and on maintaining homeostasis and energy balance in the body. Although this technique was effective, the patient was still referred to the Emergency Room. PMID:26896074
Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in Experimental Pulmonary Artery Hypertension.
Zhao, Qingyan; Deng, Hongping; Jiang, Xuejun; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Hu, Wei; Yu, Shengbo; Yang, Bo; Tang, Yanhong; Huang, Congxin
Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter (AFL), is common in patients with pulmonary arterial hypertension (PAH), who often have increased sympathetic nerve activity. Here, we tested the hypothesis that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The atrial effective refractory period and AF/AFL inducibility at baseline and after anterior right ganglionated plexi ablation were determined during left stellate ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs with or without PAH. Then, sympathetic nerve, β-adrenergic receptor densities and connexin 43 expression in atrial tissues were assessed. The sum of the window of vulnerability to AF/AFL was increased in the right atrium compared with the left atrium at baseline in the PAH dogs but not in the controls. The atrial effective refractory period dispersion was increased in the control dogs, but not in the PAH dogs, during left stellate ganglion stimulation. The voltage thresholds for inducing AF/AFL during anterior right ganglionated plexi stimulation were lower in the PAH dogs than in the controls. The AF/AFL inducibility was suppressed after ablation of the anterior right ganglionated plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and β1-adrenergic receptor densities, increased levels of nonphosphorylated connexin 43, and heterogeneous connexin 43 expression in the right atrium when compared with the control dogs. The anterior right ganglionated plexi play important roles in the induction of AF/AFL. AF/AFL induction was associated with right atrium substrate remodeling in dogs with PAH. PMID:26418021
Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology.
Liew, Reginald
Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing. PMID:24783482
Cardiac vagal control and respiratory sinus arrhythmia during hypercapnia in humans.
Brown, S J; Mundel, T; Brown, J A
Normoxic hypercapnia may increase high-frequency (HF) power in heart rate variability (HRV) and also increase respiratory sinus arrhythmia (RSA). Low-frequency (LF) power may remain unchanged. In this study, 5-min ECG recordings (N = 10) were analyzed in time and frequency domains while human subjects breathed normoxic 5% CO2 (5%CO2) or room air (RA). Tidal volume (VT), inhalatory (TI), and exhalatory (TE) times of breaths in the final minute were measured. ECG time domain measures were unaffected by CO2 inhalation (P > 0.05). Following natural logarithmic transformation (LN), LFLN was unaltered (RA: 7.14 +/- 0.95 vs. 5%CO2: 7.35 +/- 1.12, P > 0.05), and HFLN increased (RA: 7.65 +/- 1.37 vs. 5%CO2: 8.58 +/- 1.11, P < 0.05) with CO2 inhalation. When changes in total power (NU) were corrected, LF(NU) decreased (RA: 34.4 +/- 22.9 vs. 5%CO2: 23.8 +/- 23.1, P < 0.01), and HFNU increased (RA: 56.5 +/- 22.3 vs. 5%CO2: 66.8 +/- 22.9, P < 0.01) with CO2 inhalation. TI (RA: 2.0 +/- 1.0 vs. 5%CO2: 1.9 +/- 0.8 s) and TE (RA: 2.5 +/- 1.1 vs. 5%CO2: 2.4 +/- 0.9 s) remained unchanged, but VT increased with CO2 inhalation (RA: 1.1 +/- 0.3 vs. 5%CO2: 2.0 +/- 0.8 L, P < 0.001). Heart rates during inhalation (RA: 35.2 +/- 4.4, 5%CO2: 34.5 +/- 4.8 beats min(-1)) were different from heart rates during exhalation (RA: 28.8 +/- 4.4, 5%CO2: 29.1 +/- 3.1 beats min(-1)). Hypercapnia did not increase the clustering of heart beats during inhalation, and we suggest that the HF component may not adequately reflect RSA. PMID:17996126
Shock-induced termination of reentrant cardiac arrhythmias: Comparing monophasic and biphasic shock protocols
Bragard, Jean Simic, Ana; Elorza, Jorge; Grigoriev, Roman O.; Fenton, Flavio H.; Cherry, Elizabeth M.; Gilmour, Robert F.; Otani, Niels F.
In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one–dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 10{sup 6} simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation.
Shock-induced termination of reentrant cardiac arrhythmias: Comparing monophasic and biphasic shock protocols
NASA Astrophysics Data System (ADS)
Bragard, Jean; Simic, Ana; Elorza, Jorge; Grigoriev, Roman O.; Cherry, Elizabeth M.; Gilmour, Robert F.; Otani, Niels F.; Fenton, Flavio H.
In this article, we compare quantitatively the efficiency of three different protocols commonly used in commercial defibrillators. These are based on monophasic and both symmetric and asymmetric biphasic shocks. A numerical one-dimensional model of cardiac tissue using the bidomain formulation is used in order to test the different protocols. In particular, we performed a total of 4.8 × 106 simulations by varying shock waveform, shock energy, initial conditions, and heterogeneity in internal electrical conductivity. Whenever the shock successfully removed the reentrant dynamics in the tissue, we classified the mechanism. The analysis of the numerical data shows that biphasic shocks are significantly more efficient (by about 25%) than the corresponding monophasic ones. We determine that the increase in efficiency of the biphasic shocks can be explained by the higher proportion of newly excited tissue through the mechanism of direct activation.
Cardiac Repolarization Instability during Psychological Stress in Patients with Ventricular Arrhythmias
Abisse, Saddam S.; Lampert, Rachel; Burg, Mattew; Soufer, Robert; Shusterman, Vladimir
Introduction Changes in the autonomic nervous system activity (ANS) are a major trigger of life-threatening ventricular tachyarrhythmias (VTA). Mental arithmetic, a condition administered in a laboratory setting, can provide insight into the ANS effects on cardiac physiology. We examined the responses of cardiac repolarization to laboratory-induced psychological stressors in patients with implantable cardioverter defibrillators (ICDs) with the objective of identifying the indices that differentiate patients with and without subsequent VTA in follow-up. Methods Continuous ECG signals were recorded using 3 standard bipolar (Holter) leads in 56 patients (age: 63.6±11.9, female: 12%, LVEF: 32.3±11) with ICDs during mental arithmetic. The patients were separated into those with subsequent VTA during 3–4 years of follow-up (Group 1: N=9 pts) and those without VTA (Group 2: N=47 pts). Changes in repolarization (QT-interval, mean T-wave amplitude (Tamp), and T-wave area (Tarea) were analyzed during 5min of baseline, stress and recovery. The temporal instability of Tamp and Tarea was examined using the range (Δ) and variance (σ2) of beat-to-beat variations of the corresponding parameters. Results There were no significant differences in HR between the two groups at baseline (61 vs. 63 bpm, p=0.97), during stress (64 vs. 65 bpm, p=0.40), and recovery (62 vs. 61 bpm, p= 0.88). However, during mental stress and post-stress recovery ΔTamp was almost 2-fold greater in Group 1 compared with Group 2 (111 (57–203)) vs. 68 (44–94) μV p=0.04, respectively). Changes in QT-intervals were also greater in Group 1 compared with Group 2 (p=0.02). Conclusion Among patients with ICDs, changes of T-wave amplitude after psychological stress were greater in those with subsequent arrhythmic events. This might signal proarrhythmic repolarization response and help identify patients who would benefit the most from ICD implantation and proactive management. PMID:21920534
Inhibition of Angiotensin II-Induced Cardiac Hypertrophy and Associated Ventricular Arrhythmias by a p21 Activated Kinase 1 Bioactive Peptide
Lin, Wee K.; Zhang, Yanmin; Liu, Wei; Huang, Kai; Terrar, Derek A.; Solaro, R. John; Wang, Xin; Ke, Yunbo; Lei, Ming
Cardiac hypertrophy increases the risk of morbidity and mortality of cardiovascular disease and thus inhibiting such hypertrophy is beneficial. In the present study, we explored the effect of a bioactive peptide (PAP) on angiotensin II (Ang II)-induced hypertrophy and associated ventricular arrhythmias in in vitro and in vivo models. PAP enhances p21 activated kinase 1 (Pak1) activity by increasing the level of phosphorylated Pak1 in cultured neonatal rat ventricular myocytes (NRVMs). Such PAP-induced Pak1 activation is associated with a significant reduction of Ang II-induced hypertrophy in NRVMs and C57BL/6 mice, in vitro and in vivo, respectively. Furthermore, PAP antagonizes ventricular arrhythmias associated with Ang II-induced hypertrophy in mice. Its antiarrhythmic effect is likely to be involved in multiple mechanisms to affect both substrate and trigger of ventricular arrhythmogenesis. Thus our results suggest that Pak1 activation achieved by specific bioactive peptide represents a potential novel therapeutic strategy for cardiac hypertrophy and associated ventricular arrhythmias. PMID:25014109
Identification and Characterization of a Compound That Protects Cardiac Tissue from Human Ether-à-go-go-related Gene (hERG)-related Drug-induced Arrhythmias*
Potet, Franck; Lorinc, Amanda N.; Chaigne, Sebastien; Hopkins, Corey R.; Venkataraman, Raghav; Stepanovic, Svetlana Z.; Lewis, L. Michelle; Days, Emily; Sidorov, Veniamin Y.; Engers, Darren W.; Zou, Beiyan; Afshartous, David; George, Alfred L.; Campbell, Courtney M.; Balser, Jeffrey R.; Li, Min; Baudenbacher, Franz J.; Lindsley, Craig W.; Weaver, C. David; Kupershmidt, Sabina
The human Ether-à-go-go-related gene (hERG)-encoded K+ current, IKr is essential for cardiac repolarization but is also a source of cardiotoxicity because unintended hERG inhibition by diverse pharmaceuticals can cause arrhythmias and sudden cardiac death. We hypothesized that a small molecule that diminishes IKr block by a known hERG antagonist would constitute a first step toward preventing hERG-related arrhythmias and facilitating drug discovery. Using a high-throughput assay, we screened a library of compounds for agents that increase the IC70 of dofetilide, a well characterized hERG blocker. One compound, VU0405601, with the desired activity was further characterized. In isolated, Langendorff-perfused rabbit hearts, optical mapping revealed that dofetilide-induced arrhythmias were reduced after pretreatment with VU0405601. Patch clamp analysis in stable hERG-HEK cells showed effects on current amplitude, inactivation, and deactivation. VU0405601 increased the IC50 of dofetilide from 38.7 to 76.3 nm. VU0405601 mitigates the effects of hERG blockers from the extracellular aspect primarily by reducing inactivation, whereas most clinically relevant hERG inhibitors act at an inner pore site. Structure-activity relationships surrounding VU0405601 identified a 3-pyridiyl and a naphthyridine ring system as key structural components important for preventing hERG inhibition by multiple inhibitors. These findings indicate that small molecules can be designed to reduce the sensitivity of hERG to inhibitors. PMID:23033485
Calcium signalling microdomains and the t-tubular system in atrial mycoytes: potential roles in cardiac disease and arrhythmias.
Trafford, Andrew W; Clarke, Jessica D; Richards, Mark A; Eisner, David A; Dibb, Katharine M
The atria contribute 25% to ventricular stroke volume and are the site of the commonest cardiac arrhythmia, atrial fibrillation (AF). The initiation of contraction in the atria is similar to that in the ventricle involving a systolic rise of intracellular Ca(2+) concentration ([Ca(2+)](i)). There are, however, substantial inter-species differences in the way systolic Ca(2+) is regulated in atrial cells. These differences are a consequence of a well-developed and functionally relevant transverse (t)-tubule network in the atria of large mammals, including humans, and its virtual absence in smaller laboratory species such as the rat. Where T-tubules are absent, the systolic Ca(2+) transient results from a 'fire-diffuse-fire' sequential recruitment of Ca(2+) release sites from the cell edge to the centre and hence marked spatiotemporal heterogeneity of systolic Ca(2+). Conversely, the well-developed T-tubule network in large mammals ensures a near synchronous rise of [Ca(2+)](i). In addition to synchronizing the systolic rise of [Ca(2+)](i), the presence of T-tubules in the atria of large mammals, by virtue of localization of the L-type Ca(2+) channels and Na(+)-Ca(2+) exchanger antiporters on the T-tubules, may serve to, respectively, accelerate changes in the amplitude of the systolic Ca(2+) transient during inotropic manoeuvres and lower diastolic [Ca(2+)](i). On the other hand, the presence of T-tubules and hence wider cellular distribution of the Na(+)-Ca(2+) exchanger may predispose the atria of large mammals to Ca(2+)-dependent delayed afterdepolarizations (DADs); this may be a determining factor in why the atria of large mammals spontaneously develop and maintain AF. PMID:23386275
[Cardiac arrhythmias in hypertensive subjects with and without left ventricular hypertrophy compared to the circadian profile of the blood pressure].
Novo, S; Barbagallo, M; Abrignani, M G; Alaimo, G; Longo, B; Corrao, S; Nardi, E; Liquori, M; Forte, G; Raineri, A
To evaluate possible correlations between cardiac arrhythmias and circadian pattern of blood pressure (BP) and of heart rate (HR), we studied 2 groups of 20 males with stable arterial hypertension of mild to moderate entity, with (Group I) or without (Group II) left ventricular hypertrophy (LVH). In patients with LVH the mean age (56 vs 46 years), the duration of the hypertensive state (48.1 vs 15.7 months), the thickening of interventricular septum (IVS; 13.7 vs 9.6 mm) and of the posterior wall of the left ventricle (13.2 vs 9.2 mm) and the mass of LV (149.8 vs 99.7 g/m2) were significantly greater (p less than 0.01). On the contrary, the 2 groups did not show significant differences concerning casual BP determined in the morning (178.3/108.4 vs 171.5/106.2 mmHg). After a pharmacological washout of 2 weeks, patients underwent a noninvasive, intermittent, monitoring of BP (every 15 min during daytime and every 30 min from 11 pm to 7 am), using a pressure meter II Del Mar Avionics, and a continuous monitoring of ECG for 24 hours, employing an instrument 445/B Del Mar Avionics. Mean 24-hour BP was not different in the 2 groups of patients (161.7/99.0 vs 158.2/98.3 mmHg); however, patients with LVH showed a significantly greater variability of BP in the morning (7 am-3 pm), while mean 24-hour HR was significantly less (71.6 vs 78.2 b/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2150345
Role of sarcomere mechanics and Ca2+ overload in Ca2+ waves and arrhythmias in rat cardiac muscle.
ter Keurs, Henk E D J; Wakayama, Yuji; Sugai, Yoshinao; Price, Guy; Kagaya, Yutaka; Boyden, Penelope A; Miura, Masahito; Stuyvers, Bruno D M
Ca(2+) release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca(2+) load and the cytosolic Ca(2+) level. Arrhythmogenic Ca(2+) waves underlying triggered propagated contractions arise from Ca(2+) overloaded regions near damaged areas in the cardiac muscle. Ca(2+) waves can also be induced in undamaged muscle, in regions with nonuniform excitation-contraction (EC) coupling by the cycle of stretch and release in the border zone between the damaged and intact regions. We hypothesize that rapid shortening of sarcomeres in the border zone during relaxation causes Ca(2+) release from troponin C (TnC) on thin filaments and initiates Ca(2+) waves. Elimination of this shortening will inhibit the initiation of Ca(2+) waves, while SR Ca(2+) overload will enhance the waves. Force, sarcomere length (SL), and [Ca(2+)](i) were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca(2+)] 10 mM (HC), or HC containing BDM, was used to weaken a 300 mum long muscle segment. Trains of electrical stimuli were used to induce Ca(2+) waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca(2+) waves (V(prop)) were studied. Sarcomere shortening was uniform prior to activation. HC induced spontaneous diastolic sarcomere contractions in the jet region and attenuated twitch sarcomere shortening; HC+ butanedione monoxime (BDM) caused stretch only in the jet region. Stimulus trains induced Ca(2+) waves, which started inside the HC jet region during twitch relaxation. Ca(2+) waves started in the border zone of the BDM jet. The initial local [Ca(2+)](i) rise of the waves by HC was twice that by BDM. The waves propagated at a V(prop) of 2.0 +/- 0.2 mm/sec. Arrhythmias occurred frequently in trabeculae following exposure to the HC jet. Stretch early during relaxation, which reduced sarcomere shortening in the weakened regions, substantially
[New diagnostic tools for arrhythmias].
Teres, C; Burri, H
Cardiac arrhythmias are common conditions that often manifest themselves intermittently, thus complicating their diagnosis, particularly in the ambulatory setting. Recently, technological advances have facilitated public access to health applications and devices. This article reviews the available technologies and analyses their usefulness for the diagnosis of arrhythmias in the context of everyday clinical practice. PMID:26182638
How are European patients at risk of malignant arrhythmias or sudden cardiac death identified and informed about their risk profile: results of the European Heart Rhythm Association survey.
Proclemer, Alessandro; Bongiorni, Maria Grazia; Dagres, Nikolaos; Sciaraffia, Elena; Todd, Derick; Blomstrom-Lundqvist, Carina
The purpose of this EP wire is to examine clinical practice in the field of screening of patients of risk of ventricular arrhythmias and/or sudden cardiac death (SCD) in European countries. A systematic screening programme existed in the majority of centres and was organized by a multidisciplinary dedicated team or by an activity programme of implantable cardioverter-defibrillator (ICD) or heart failure clinics. In particular, high-risk subgroups of patients with ischaemic and non-ischaemic cardiomyopathy ICD implantation are considered strongly indicated within 90 days of myocardial revascularization or initial diagnosis. Cardiac magnetic resonance imaging appears as an important tool to better characterize the left ventricular arrhythmogenic substrate in patients at risk of SCD. PMID:26023178
Hemodynamics in fetal arrhythmia.
Sonesson, Sven-Erik; Acharya, Ganesh
Fetal arrhythmias are among the few conditions that can be managed in utero. However, accurate diagnosis is essential for appropriate management. Ultrasound-based imaging methods can be used to study fetal heart structure and function noninvasively and help to understand fetal cardiovascular pathophysiology, and they remain the mainstay of evaluating fetuses with arrhythmias in clinical settings. Hemodynamic evaluation using Doppler echocardiography allows the elucidation of the electrophysiological mechanism and helps to make an accurate diagnosis. It can also be used as a tool to understand fetal cardiac pathophysiology, for assessing fetal condition and monitoring the effect of antiarrhythmic treatment. This narrative review describes Doppler techniques that are useful for evaluating fetal cardiac rhythms to refine diagnosis and provides an overview of hemodynamic changes observed in different types of fetal arrhythmia. PMID:26660845
Bartonella vinsonii subsp. berkhoffii and Related Members of the Alpha Subdivision of the Proteobacteria in Dogs with Cardiac Arrhythmias, Endocarditis, or Myocarditis
Breitschwerdt, Edward B.; Atkins, Clarke E.; Brown, Talmage T.; Kordick, Dorsey L.; Snyder, Patti S.
Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis, Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude that B. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs. PMID:10523564
Arrhythmias in Complex Congenital Heart Disease
Hayward, Robert M.; Tseng, Zian H.
Late after surgical repair of complex congenital heart disease, atrial arrhythmias are a major cause of morbidity, and ventricular arrhythmias and sudden cardiac death are a major cause of mortality. The six cases in this article highlight common challenges in the management of arrhythmias in the adult congenital heart disease population. PMID:25197326
TRPA1 and Sympathetic Activation Contribute to Increased Risk of Triggered Cardiac Arrhythmias in Hypertensive Rats Exposed to Diesel Exhaust
Haykal-Coates, Najwa; Winsett, Darrell W.; Krantz, Q. Todd; King, Charly; Costa, Daniel L.; Farraj, Aimen K.
Background: Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias. Objective: We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia. Methods: Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m3 (high) or 150 μg/m3 (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored. Results: Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE–exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia. Conclusions: These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk. PMID:21377951
Arrhythmias in pulmonary arterial hypertension.
Rajdev, Archana; Garan, Hasan; Biviano, Angelo
Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914
Arrhythmias in Pulmonary Arterial Hypertension
Rajdev, Archana; Garan, Hasan; Biviano, Angelo
Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914
TRPA1 and Sympathetic Activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust
Background -Diesel exhaust (DE), which is emitted from on-and off-road sources, is a complex mixture of toxic gaseous and particulate components that results in adverse cardiovascular effects. Arrhythmias, which are often triggered in the hours and days following exposure, are on...
Changes in heart rate, arrhythmia frequency, and cardiac biomarker values in horses during recovery after a long-distance endurance ride.
Flethøj, Mette; Kanters, Jørgen K; Haugaard, Maria M; Pedersen, Philip J; Carstensen, Helena; Balling, Johanne D; Olsen, Lisbeth H; Buhl, Rikke
OBJECTIVE To evaluate heart rate, heart rate variability, and arrhythmia frequency as well as changes in cardiac biomarker values and their association with heart rate in horses before and after an endurance ride. DESIGN Cross-sectional study. ANIMALS 28 Arabian horses competing in a 120- or 160-km endurance ride. PROCEDURES ECG recordings were obtained from each horse before (preride) and after (recovery) an endurance ride to evaluate changes in heart rate and the SD of normal R-R intervals (SDNN) during the initial 12 hours of recovery. Frequencies of supraventricular and ventricular premature complexes before and after the ride were evaluated. Blood samples were obtained before the ride and twice during recovery. Hematologic analyses included measurement of serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity. RESULTS Heart rate was significantly increased and SDNN was decreased during the recovery versus preride period. Frequency of ventricular premature complexes increased during recovery, albeit not significantly, whereas frequency of supraventricular premature complexes was not significantly different between preride and recovery periods. Serum cardiac troponin I concentration and creatine kinase isoenzyme MB activity were significantly increased in the recovery versus preride period. No associations were identified between cardiac biomarkers and velocity, distance, or mean heart rate. CONCLUSIONS AND CLINICAL RELEVANCE Heart rate increased and SDNN decreased in horses after completion of an endurance ride. These and other cardiac changes suggested that prolonged exercise such as endurance riding might have cardiac effects in horses. Additional studies are needed to clarify the clinical relevance of the findings. PMID:27074612
Bisbal, F; Mont, L
Regular exercise provides substantial health benefits, mostly by reducing cardiovascular risk factors. However, it may also trigger acute cardiac events and cause sudden cardiac death in individuals with a pre-existing condition. In an otherwise healthy population, intense regular exercise may lead to morphological and electrical cardiac adaptations commonly referred as "athlete's heart." Recent data suggest that this may itself produce structural changes of atrial and ventricular myocardium with enlargement and fibrosis, creating the substrate for development of arrhythmias in apparently healthy athletes. The state of the art in this controversial issue is reviewed. PMID:22782729
Fetal and Neonatal Arrhythmias.
Jaeggi, Edgar; Öhman, Annika
Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID:26876124
Characterization of Cardiac Anoctamin1 Ca²⁺-Activated Chloride Channels and Functional Role in Ischemia-Induced Arrhythmias.
Ye, Zhen; Wu, Ming-Ming; Wang, Chun-Yu; Li, Yan-Chao; Yu, Chang-Jiang; Gong, Yuan-Feng; Zhang, Jun; Wang, Qiu-Shi; Song, Bin-Lin; Yu, Kuai; Hartzell, H Criss; Duan, Dayue Darrel; Zhao, Dan; Zhang, Zhi-Ren
Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride (Cl(-)) channel (CaCC) in variety tissues of many species. Whether ANO1 expresses and functions as a CaCC in cardiomyocytes remain unknown. The objective of this study is to characterize the molecular and functional expression of ANO1 in cardiac myocytes and the role of ANO1-encoded CaCCs in ischemia-induced arrhythmias in the heart. Quantitative real-time RT-PCR, immunofluorescence staining assays, and immunohistochemistry identified the molecular expression, location, and distribution of ANO1 in mouse ventricular myocytes (mVMs). Patch-clamp recordings combined with pharmacological analyses found that ANO1 was responsible for a Ca(2+)-activated Cl(-) current (I(Cl.Ca)) in cardiomyocytes. Myocardial ischemia led to a significant increase in the current density of I(Cl.Ca), which was inhibited by a specific ANO1 inhibitor, T16A(inh)-A01, and an antibody targeting at the pore area of ANO1. Moreover, cardiomyocytes isolated from mice with ischemia-induced arrhythmias had an accelerated early phase 1 repolarization of action potentials (APs) and a deeper "spike and dome" compared to control cardiomyocytes from non-ischemia mice. Application of the antibody targeting at ANO1 pore prevented the ischemia-induced early phase 1 repolarization acceleration and caused a much shallower "spike and dome". We conclude that ANO1 encodes CaCC and plays a significant role in the phase 1 repolarization of APs in mVMs. The ischemia-induced increase in ANO1 expression may be responsible for the increased density of I(Cl.Ca) in the ischemic heart and may contribute, at least in part, to ischemia-induced arrhythmias. PMID:24962810
Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats
Sharma, Ashish Kumar; Kishore, Kunal; Sharma, Divya; Srinivasan, B.P; Agarwal, Shyam Sunder; Sharma, Ashok; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh
The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract (150, 250, and 450 mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The PQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia. PMID:23554702
Hexabromocyclododecane exposure induces cardiac hypertrophy and arrhythmia by inhibiting miR-1 expression via up-regulation of the homeobox gene Nkx2.5.
Wu, Meifang; Wu, Di; Wang, Chonggang; Guo, Zhizhun; Li, Bowen; Zuo, Zhenghong
Hexabromocyclododecane (HBCD) is one of the most widely used brominated flame retardants. Although studies have reported that HBCD can cause a wide range of toxic effects on animals including humans, limited information can be found about its cardiac toxicity. In the present study, zebrafish embryos were exposed to HBCD at low concentrations of 0, 2, 20 and 200 nM. The results showed that HBCD exposure could induce cardiac hypertrophy and increased deposition of collagen. In addition, disordered calcium (Ca(2+)) handling was observed in H9C2 rat cardiomyocyte cells exposed to HBCD. Using small RNA sequencing and real-time quantitative PCR, HBCD exposure was shown to induce significant changes in the miRNA expression profile associated with the cardiovascular system. Further findings indicated that miR-1, which was depressed by Nkx2.5, might play a fundamental role in mediating cardiac hypertrophy and arrhythmia via its target genes Mef2a and Irx5 after HBCD treatment. HBCD exposure induced an arrhythmogenic disorder, which was triggered by the imbalance of Ryr2, Serca2a and Ncx1 expression, inducing Ca(2+) overload in the sarcoplasmic reticulum and high Ca(2+)-ATPase activities in the H9C2 cells. PMID:26476318
... from American Heart Association Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... terms: SCA, sudden cardiac death (SCD), sudden death, arrhythmias, ... ventricular fibrillation, defibrillator, automatic cardiac defibrillator ( ...
Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A
The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366
Genetics of inherited primary arrhythmia disorders
Spears, Danna A; Gollob, Michael H
A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. PMID:26425105
Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†
Huikuri, Heikki V.; Raatikainen, M.J. Pekka; Moerch-Joergensen, Rikke; Hartikainen, Juha; Virtanen, Vesa; Boland, Jean; Anttonen, Olli; Hoest, Nis; Boersma, Lucas V.A.; Platou, Eivind S.; Messier, Marc D.; Bloch-Thomsen, Poul-Erik
Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint. Conclusion Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI. PMID:19155249
High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.
Gilchrist, Kristin H; Lewis, Gregory F; Gay, Elaine A; Sellgren, Katelyn L; Grego, Sonia
Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. PMID:26232523
Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.
Song, LouJin; Awari, Daniel W; Han, Elizabeth Y; Uche-Anya, Eugenia; Park, Seon-Hye E; Yabe, Yoko A; Chung, Wendy K; Yazawa, Masayuki
Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics. PMID:25769651
Janse, M J; Rosen, M R
A historical overview is given on the techniques to record the electrical activity of the heart, some anatomical aspects relevant for the understanding of arrhythmias, general mechanisms of arrhythmias, mechanisms of some specific arrhythmias and nonpharmacological forms of therapy. The unravelling of arrhythmia mechanisms depends, of course, on the ability to record the electrical activity of the heart. It is therefore no surprise that following the construction of the string galvanometer by Einthoven in 1901, which allowed high-fidelity recording of the body surface electrocardiogram, the study of arrhythmias developed in an explosive way. Still, papers from McWilliam (1887), Garrey (1914) and Mines (1913, 1914) in which neither mechanical nor electrical activity was recorded provided crucial insights into re-entry as a mechanism for atrial and ventricular fibrillation, atrioventricular nodal re-entry and atrioventricular re-entrant tachycardia in hearts with an accessory atrioventricular connection. The components of the electrocardiogram, and of extracellular electrograms directly recorded from the heart, could only be well understood by comparing such registrations with recordings of transmembrane potentials. The first intracellular potentials were recorded with microelectrodes in 1949 by Coraboeuf and Weidmann. It is remarkable that the interpretation of extracellular electrograms was still controversial in the 1950s, and it was not until 1962 that Dower showed that the transmembrane action potential upstroke coincided with the steep negative deflection in the electrogram. For many decades, mapping of the spread of activation during an arrhythmia was performed with a "roving" electrode that was subsequently placed on different sites on the cardiac surface with a simultaneous recording of another signal as time reference. This method could only provide reliable information if the arrhythmia was strictly regular. When multiplexing systems became available in
Exercise and Inherited Arrhythmias.
Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D
Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise. PMID:26927864
NASPE expert consensus document: use of i.v. (conscious) sedation/analgesia by nonanesthesia personnel in patients undergoing arrhythmia specific diagnostic, therapeutic, and surgical procedures.
Bubien, R S; Fisher, J D; Gentzel, J A; Murphy, E K; Irwin, M E; Shea, J B; Dick, M; Ching, E; Wilkoff, B L; Benditt, D G
Use of IV (Conscious) Sedation/Analgesia by Nonanesthesia Personnel in Patients Undergoing Arrhythmia Specific Diagnostic, Therapeutic, and Surgical Procedures. This article is intended to inform practitioners, payers, and other interested parties of the opinion of the North American Society of Pacing and Electrophysiology (NASPE) concerning evolving areas of clinical practice or technologies or both, that are widely available or are new to the practice community. Expert consensus documents are so designated because the evidence base and experience with the technology or clinical practice are not yet sufficiently well developed, or rigorously controlled trials are not yet available that would support a more definitive statement. This article has been endorsed by the American College of Cardiology, October 1997. PMID:9507538
Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia.
Milstein, Michelle L; Musa, Hassan; Balbuena, Daniela Ponce; Anumonwo, Justus M B; Auerbach, David S; Furspan, Philip B; Hou, Luqia; Hu, Bin; Schumacher, Sarah M; Vaidyanathan, Ravi; Martens, Jeffrey R; Jalife, José
The cardiac electrical impulse depends on an orchestrated interplay of transmembrane ionic currents in myocardial cells. Two critical ionic current mechanisms are the inwardly rectifying potassium current (I(K1)), which is important for maintenance of the cell resting membrane potential, and the sodium current (I(Na)), which provides a rapid depolarizing current during the upstroke of the action potential. By controlling the resting membrane potential, I(K1) modifies sodium channel availability and therefore, cell excitability, action potential duration, and velocity of impulse propagation. Additionally, I(K1)-I(Na) interactions are key determinants of electrical rotor frequency responsible for abnormal, often lethal, cardiac reentrant activity. Here, we have used a multidisciplinary approach based on molecular and biochemical techniques, acute gene transfer or silencing, and electrophysiology to show that I(K1)-I(Na) interactions involve a reciprocal modulation of expression of their respective channel proteins (Kir2.1 and Na(V)1.5) within a macromolecular complex. Thus, an increase in functional expression of one channel reciprocally modulates the other to enhance cardiac excitability. The modulation is model-independent; it is demonstrable in myocytes isolated from mouse and rat hearts and with transgenic and adenoviral-mediated overexpression/silencing. We also show that the post synaptic density, discs large, and zonula occludens-1 (PDZ) domain protein SAP97 is a component of this macromolecular complex. We show that the interplay between Na(v)1.5 and Kir2.1 has electrophysiological consequences on the myocardium and that SAP97 may affect the integrity of this complex or the nature of Na(v)1.5-Kir2.1 interactions. The reciprocal modulation between Na(v)1.5 and Kir2.1 and the respective ionic currents should be important in the ability of the heart to undergo self-sustaining cardiac rhythm disturbances. PMID:22509027
SU-C-303-06: Treatment Planning Study for Non-Invasive Cardiac Arrhythmia Ablation with Scanned Carbon Ions in An Animal Model
Eichhorn, A; Constantinescu, A; Prall, M; Kaderka, R; Durante, M; Graeff, C; Lehmann, H I; Takami, M; Packer, D L; Lugenbiel, P; Thomas, D; Richter, D; Bert, C
Purpose: Scanned carbon ion beams might offer a non-invasive alternative treatment for cardiac arrhythmia, which are a major health-burden. We studied the feasibility of this procedure in an animal model. The underlying treatment planning and motion mitigation strategies will be presented. Methods: The study was carried out in 15 pigs, randomly distributed to 3 target groups: atrioventricular node (AVN, 8 animals with 25, 40, and 55 Gy target dose), left ventricular free-wall (LV, 4 animals with 40 Gy) and superior pulmonary vein (SPV, 3 animals with 40 Gy). Breathing motion was suppressed by repeated enforced breathholds at end exhale. Cardiac motion was mitigated by an inhomogeneous rescanning scheme with up to 15 rescans. The treatment planning was performed using the GSI in-house software TRiP4D on cardiac-gated 4DCTs, applying a range-considering ITV based on an extended CTV. For AVN and SPV isotropic 5 mm margins were applied to the CTV, while for the LV 2mm+2% range margins were used. The opposing fields for AVN and LV targets were optimized independently (SFUD), while SPV treatments were optimized as IMPT deliveries, including dose restrictions to the radiosensitive AVN. Results: Median value of D{sub 95} over all rescanning simulations was 99.1% (AVN), 98.0% (SPV) and 98.3% (LV) for the CTV and 94.7% (AVN) and 92.7% (SPV) for the PTV, respectively. The median D{sub 5}-D{sub 95} was improved with rescanning compared to unmitigated delivery from 13.3 to 6.5% (CTV) and from 23.4 to 11.6% (PTV). ICRP dose limits for aorta, trachea, esophagus and skin were respected. The maximal dose in the coronary arteries was limited to 30 Gy. Conclusion: We demonstrated the feasibility of a homogeneous dose delivery to different cardiac structures in a porcine model using a time-optimized inhomogeneous rescanning scheme. The presented treatment planning strategies were applied in a pig study with the analysis ongoing. Funding: This work was supported in part by the
An evaluation of potential signals for ventricular arrhythmia and cardiac arrest with dolasetron, ondansetron, and granisetron in the fda combined spontaneous reporting system/adverse event reporting system
Schnell, Frederick M.; Coop, Andrew J.
arrhythmias and cardiac arrest. The PRR, used as a parameter to detect a potential signal within the database, was 3.23, 1.31, and 1.13 for dolasetron, ondansetron, and granisetron, respectively. The number of observed ventricular arrhythmias and cardiac arrests was ∼3-fold higher with dolasetron compared with the expected value (calculated by dividing the individual agent's total number of events reported by the proportion of adverse events for all agents combined). The results for dolasetron fulfilled the criteria we used to define a potential signal. Conclusions: This analysis detected a potential signal for ventricular arrhythmiasand cardiac arrest with dolasetron, but not with ondansetron or granisetron. However, there are limitations of a PRR analysis, which include only measuring cases that have been reported, providing relative frequencies instead of actual rates, and not providing information on the severity of adverse events or causal relationships. In addition, our analysis does not include consideration of concomitant medications, and only 2 search terms were used. Errors in identifying potential signals may also include confounding factors, such as the underlying disease, potential confusion with reporting under trade and generic names, and potential multiple reporting of the same case. PMID:24790242
Left regional cardiac perfusion in vitro with platelet-activating factor, norepinephrine and K+ reveals that ischaemic arrhythmias are caused by independent effects of endogenous 'mediators' facilitated by interactions, and moderated by paradoxical antagonism
Baker, Kathryn E; Curtis, Michael J
Various putative drug targets for suppression of ischaemia-induced ventricular fibrillation (VF) have been proposed, but therapeutic success in the suppression of sudden cardiac death (SCD) has been disappointing. Platelet-activating factor (PAF) is a known component of the ischaemic milieu. We examined its arrhythmogenic activity, and its interaction with two other putative mediators, norepinephrine and K+, using an ischaemia-free in vitro heart bioassay, and a specific PAF antagonist (BN-50739). PAF (0.1–100 nmol) was administered selectively to the left coronary bed of rat isolated hearts using a specially designed catheter. In some hearts, PAF was administered to the left coronary bed during concomitant regional perfusion with norepinephrine and/or K+. In separate studies, PAF accumulation in the perfused cardiac tissue was evaluated using 3H-PAF. PAF evoked ventricular arrhythmias concentration-dependently (P<0.05). It also widened QT interval and reduced coronary flow selectively in the PAF-exposed left coronary bed (both P<0.05). Two exposures of hearts to PAF were necessary to evoke the QT and rhythm effects. The PAF-induced arrhythmias and coronary vasoconstriction were partially suppressed by the PAF antagonist BN-50739 (10 μM), although BN-50739 itself widened QT interval. K+ (8 and 15 mM) unexpectedly antagonised the arrhythmogenic effects of PAF without itself eliciting arrhythmias (P<0.05). Norepinephrine (0.1 μM) had little or no effect on the actions of PAF, while failing to evoke arrhythmias itself. Nevertheless, the combination of 15 mM K+ and 0.1 μM norepinephrine evoked arrhythmias of a severity similar to arrhythmias evoked by PAF alone, without adding to or diminishing the arrhythmogenic effects of PAF. 3H-PAF accumulated in the cardiac tissue, with 43±5% still present 5 min after bolus administration, accounting for the need for two exposures of the heart to PAF for evocation of arrhythmias. Thus, PAF, by activating specific receptors
Non-Invasive Drosophila ECG Recording by Using Eutectic Gallium-Indium Alloy Electrode: A Feasible Tool for Future Research on the Molecular Mechanisms Involved in Cardiac Arrhythmia
Kuo, Po-Hung; Tzeng, Te-Hsuen; Huang, Yi-Chun; Chen, Yu-Hao; Chang, Yi-Chung; Ho, Yi-Lwun; Wu, June-Tai; Lee, Hsiu-Hsian; Lai, Po-Jung; Liu, Kwei-Yan; Cheng, Ya-Chen; Lu, Shey-Shi
on the molecular mechanism involved in cardiac arrhythmia, as well as research related to drug screening and development. PMID:25226390
Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients with Chronic Myocardial Infarction: Early Evidence
Cokic, Ivan; Kali, Avinash; Yang, Hsin-Jung; Yee, Raymond; Tang, Richard; Tighiouart, Mourad; Wang, Xunzhang; Jackman, Warren S.; Chugh, Sumeet S.; White, James A.; Dharmakumar, Rohan
BACKGROUND Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electrical behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias (mVA) in humans with CMI is unknown. METHODS AND RESULTS CMI patients (n=94) who underwent late-gadolinium-enhanced CMR prior to ICD implantation for primary and secondary prevention were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession (bSSFP) images and conventional CMR and ECG mVA parameters for the prediction of primary combined outcome (appropriate ICD therapy, survived cardiac arrest or sudden cardiac death) were studied. The use of HIC within CMI on bSSFP as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range (IQR) of 540) days after ICD placement. Of the 19 patients meeting the primary endpoint, 18 were classified as HIC+, while only 1 was HIC−. Among the cohort in whom the primary endpoint was not met, there were 28 HIC+ and 47 HIC− patients. ROC analysis demonstrated an additive predictive value of HIC for mVAs with an increased AUC to 0.87 when added to LVEF (LVEF alone 0.68). Both CMR and histological validation studies performed in canines demonstrated that HIC regions in bSSFP images within CMI likely result from iron depositions. CONCLUSIONS Hypointense cores within CMI on bSSFP CMR can be used as a marker of iron deposition and yields incremental information toward improved prediction of mVA. PMID:26259581
Weather-induced ischemia and arrhythmia in patients undergoing cardiac rehabilitation: another difference between men and women
NASA Astrophysics Data System (ADS)
Schneider, Alexandra; Schuh, Angela; Maetzel, Friedrich-Karl; Rückerl, Regina; Breitner, Susanne; Peters, Annette
Given the accumulating evidence that people with underlying heart disease are a particularly vulnerable group for triggers like changing meteorological parameters, the objective of this longitudinal study was to analyze the influence of weather parameters on blood pressure, arrhythmia and ischemia in cardiovascular patients. A panel study with repeated measurements was conducted in a rehabilitation clinic in Timmendorfer Strand (Baltic Sea, Germany) with 872 cardiovascular patients. Heart rate, blood pressure and electrocardiography changes were measured during repeated bicycle ergometries. Generalized Estimating Equations were used for regression analyses of immediate, delayed and cumulative influences of the daily measured meteorological data. For men, a decrease in air temperature and in water vapor pressure doubled the risk of ST-segment depression during ergometry [odds ratio (OR) for 1 day delay: 1.88 (1.24; 2.83) for air temperature] with a delay of 1-2 days. For women, an increase of their heart rate before the start of the ergometry [same day: 4.36 beats/min (0.99; 7.74) for air temperature] and a 2- to 3-fold higher risk for ventricular ectopic beats [1 day delay: OR 2.43 (1.17; 5.05) for air temperature] was observed with an increase in temperature and water vapor pressure in almost all analyzed time-windows. The study indicates that meteorological parameters can induce changes in heart function which may lead to adverse cardiovascular events especially in susceptible, diseased individuals. The observed effect on ST-segment depression could be a link between the association of weather changes and cardiovascular morbidity and mortality.
Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human
Roux-Buisson, Nathalie; Cacheux, Marine; Fourest-Lieuvin, Anne; Fauconnier, Jeremy; Brocard, Julie; Denjoy, Isabelle; Durand, Philippe; Guicheney, Pascale; Kyndt, Florence; Leenhardt, Antoine; Le Marec, Hervé; Lucet, Vincent; Mabo, Philippe; Probst, Vincent; Monnier, Nicole; Ray, Pierre F.; Santoni, Elodie; Trémeaux, Pauline; Lacampagne, Alain; Fauré, Julien; Lunardi, Joël; Marty, Isabelle
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans. PMID:22422768
Arrhythmias in the Muscular Dystrophies
Rajdev, Archana; Groh, William J.
Synopsis In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occur with variable prevalence mirroring the phenotypic variability seen among and within the various hereditary myopathies. These patients are at risk for development for bradyarrhythmias and tachyarrhythmias including sudden cardiac death. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The non-cardiac manifestations can lead to delayed recognition of symptoms (limited mobility and respiratory weakness masking cardiac manifestations), affect decision to implant prophylactic device (quantity vs. quality of life) and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications. PMID:26002394
Jurkovicová, O; Cagán, S
Reperfusion arrhythmias originate as a consequence of the complex of cellular and humoral reactions accompanying the opening of coronary artery. As the primary cause of their generation are considered the chemically defined substances that are produced and accumulated in myocardium during reperfusion. The key role is ascribed to free oxygen radicals but of importance are also other substances such as calcium, thrombin, platelet activating factor, inositol triphosphate, angiotensin II and others. These chemical mediators of reperfusion arrhythmias operate as modulators of cellular electrophysiology causing the complex changes at the level of ion channels. It is supposed that in the genesis of reperfusion arrhythmias unlike ischemic arrhytmias operate nonreentrant mechanisms such as abnormal or enhanced automacy and triggered activity due to afterdepolarizations. As a typical reperfusion arrhythmia is considered an early (within 6 hours after start of thrombolysis), frequent (> 30 episodes/hour) and repetitive (occurring during > 3 consecutive hours) accelerated idioventricular rhythm (AIVR). AIVR with such characteristics has a high specificity and positive predictive accuracy but relative low sensitivity as a predictor of reperfusion. Thus, in occurrence of AIVR, recanalization of infarction-related coronary artery is very probable, but in absence of AIVR, reperfusion is still not excluded. The following arrhythmias are regarded also as markers of reperfusion: frequent premature ventricular complexes (> twofold increase in frequency within 90 minutes after the start of thrombolysis), a significant increase of episodes in nonsustained ventricular tachycardia, sinus bradycardia and probably also high-degree atrioventricular blocks. At present, there is no definite evidence, as to whether sustained ventricular tachycardia and especially ventricular fibrillation can be caused by reperfusion. Reperfusion arrhythmias are an important noninvasive marker of successful
Feasibility of spinal cord stimulation in angina pectoris in patients with chronic pacemaker treatment for cardiac arrhythmias.
Ekre, Olof; Börjesson, Mats; Edvardsson, Nils; Eliasson, Tore; Mannheimer, Clas
Spinal cord stimulation (SCS) has been used since 1985 as additional symptom-relieving treatment for patients with severe angina pectoris despite optimal conventional medical and invasive treatment. SCS has antiischemic effects and is safe and effective in long-term use. Several patients with coronary artery disease also suffer from disorders that necessitate the use of a cardiac permanent pacemaker (PPM). The combination of SCS and PPM has previously been considered hazardous because of possible false inhibition of the PPM. To assess if thoracic SCS and PPM can be safely combined in patients with refractory angina pectoris, 18 patients treated with both SCS and PPM were tested. The PPM settings were temporarily modified to increase the probability of interference, while the SCS intensity (used in bipolar mode) was increased to the maximum level tolerated by the patient. Any sign of inhibition of the ventricular pacing was recorded by continuous ECG monitoring. With the aid of a questionnaire, symptoms of interference during long-term treatment were evaluated. No patient had signs of inhibition during the tests. Reprogramming of the pacemaker because of the test results was not needed in any of the patients. The long-term follow-up data revealed no serious events. This study indicates that bipolar SCS and PPM can be safely combined in patients with refractory angina pectoris. However, individual testing is mandatory to ascertain safety in each patient. A testing procedure for patients in need of SCS and PPM is suggested in this article. PMID:14622316
Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations
Lalani, Seema R.; Liu, Pengfei; Rosenfeld, Jill A.; Watkin, Levi B.; Chiang, Theodore; Leduc, Magalie S.; Zhu, Wenmiao; Ding, Yan; Pan, Shujuan; Vetrini, Francesco; Miyake, Christina Y.; Shinawi, Marwan; Gambin, Tomasz; Eldomery, Mohammad K.; Akdemir, Zeynep Hande Coban; Emrick, Lisa; Wilnai, Yael; Schelley, Susan; Koenig, Mary Kay; Memon, Nada; Farach, Laura S.; Coe, Bradley P.; Azamian, Mahshid; Hernandez, Patricia; Zapata, Gladys; Jhangiani, Shalini N.; Muzny, Donna M.; Lotze, Timothy; Clark, Gary; Wilfong, Angus; Northrup, Hope; Adesina, Adekunle; Bacino, Carlos A.; Scaglia, Fernando; Bonnen, Penelope E.; Crosson, Jane; Duis, Jessica; Maegawa, Gustavo H.B.; Coman, David; Inwood, Anita; McGill, Jim; Boerwinkle, Eric; Graham, Brett; Beaudet, Art; Eng, Christine M.; Hanchard, Neil A.; Xia, Fan; Orange, Jordan S.; Gibbs, Richard A.; Lupski, James R.; Yang, Yaping
The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3–9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3–9. Additionally, a homozygous exons 4–6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3–9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations. PMID:26805781
[Rational management of arrhythmias].
González-Hermosillo, J A; Colín, L; Iturralde, P; Romero, L
Despite the development of better diagnostic techniques and new modes of therapy, management of cardiac arrhythmias is still difficult. The lack of standardization in the indications of each technique has increased the risk of overtreatment and unnecessary cost. This paper describes the minimal requirements necessary for the different techniques and the appropriate information that should be collected from each. A well taken clinical history and a 12-lead EKG give very important information for the decision on when and how to treat. PMID:2091549
In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias.
Wold, Loren E; Simkhovich, Boris Z; Kleinman, Michael T; Nordlie, Margaret A; Dow, Joan S; Sioutas, Constantinos; Kloner, Robert A
Exposure to ultrafine particles (UFPs) by inhalation increases the number and severity of cardiac events. The specific mechanism(s) of action are unknown. This study was designed to examine whether UFPs could exert a direct effect on the cardiovascular system without dependence upon lung-mediated responses. The direct effects of UFPs were determined in normal rats (infused intravenously with UFPs), and in the isolated Langendorff perfused rat heart. UFPs from either ambient air (UFAAs) or diesel engine exhaust (UFDGs) were studied. Infusion of UFDGs prepared in our laboratory caused ventricular premature beats (VPBs) in 2 of 3 rats in vivo. Ejection fraction increased slightly (approximately 4.5%) in rats receiving UFPAA and was unchanged in the UFDG and saline groups in vivo. In the isolated rat heart, perfused according to Langendorff, UFDGs caused a marked increase in left-ventricular end-diastolic pressure (LVEDP; from 12.0 +/- 4.6 mmHg to 24.8 +/- 11.2 mmHg, p < 0.05) after 30 min of exposure. UFPs isolated from industrial diesel particulate matter (UFIDs), obtained from the National Institute of Standards and Technology, caused a significant decrease in left-ventricular systolic pressure (LVSP; from 85.7 +/- 4.0 mmHg to 37.9 +/- 20.3 mmHg, p < 0.05) and +/- dP/dt (from 2,365 +/- 158 mmHg/s to 1,188 +/- 858 mmHg/s, p < 0.05) at 30 min after the start of infusion. This effect was absent when the soluble fraction (containing no particles) isolated from the UFIDs was studied. These findings indicate that UFPs can have direct effects on the cardiovascular system that are independent of effects of particles on the lungs. PMID:16845184
Antipsychotic Drugs and the Risk of Ventricular Arrhythmia and/or Sudden Cardiac Death: A Nation‐wide Case‐Crossover Study
Wu, Chi‐Shin; Tsai, Yu‐Ting; Tsai, Hui‐Ju
Background Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD. Methods and Results We conducted a case‐crossover study using a nation‐wide population‐based sample obtained from Taiwan's National Health Insurance Research Database. A total of 17 718 patients with incident VA and/or SCD were enrolled. Conditional logistic regression models were applied to examine the effects of antipsychotic drug use on the risk of VA/SCD during various case and control time windows of 7, 14, and 28 days. The effect of the potency of a human ether‐à‐go‐go‐related gene (hERG) potassium channel blockade was also assessed. Antipsychotic drug use was associated with a 1.53‐fold increased risk of VA and/or SCD. Antipsychotic drugs with increased risk included clothiapine, haloperidol, prochlorperazine, thioridazine, olanzapine, quetiapine, risperidone, and sulpiride. The association was significantly higher among those with short‐term use. Antipsychotics with a high potency of the hERG potassium channel blockade had the highest risk of VA and/or SCD. Conclusion Use of antipsychotic drugs is associated with an increased risk of VA and/or SCD. Careful evaluations of the risks and benefits of antipsychotic treatment are highly recommended. PMID:25713294
The Comparison of the Effects of Epidural Bupivacaine and Levobupivacaine on the Autonomic Nervous System and Cardiac Arrhythmia Parameters in Inguinal Hernia Surgeries
Demir, Aynur; Kaya, Ayşe Günay; Yavuz, Bünyamin; Kantekin, Çiğdem Ünal; Başar, Hülya
Objective The aim of this study is to investigate the effects of bupivacaine and levobupivacaine, used to create epidural anaesthesia in inguinal hernia operations, on heart rate variability and cardiac arrhythmia parameters. Methods Sixty male patients of the American Society of Anesthesiology (ASA) I–II group, scheduled to be operated on for inguinal hernia surgery with epidural anaesthesia, were randomly divided into two groups. The patients, with a 12-channel Holter recorder (Rozinn RZ153+12-USA) attached 1 hour before the operation to record until the end of the surgery, were taken into the preparation room and anaesthetised. In group L (n=30), 17 mL of 0.5% levobupivacaine (Chirocain 0.5%-Abbot, El-verum, Norway) was given into the epidural space within 10 minutes, versus 17 mL of 0.5% bupivacaine in (Marcain 0.5%, Astra Zeneca, İstanbul, Turkey) group B (n=30). After 30 minutes, when there was enough block, the operation had been started. Holter recordings, starting 1 hour before the anaesthetic procedure and completed by the end of the operations, were transferred to the computer. The records were evaluated by the cardiologists. Results When analysing the frequency effect measurement results of the heart rate variability, it was seen that neither of the medications created any statistically significant change in or among the groups in total, very-low-frequency (VLF), low-frequency (LF), high-frequency (HF) and LF/HF ratio levels. Only normalised low-frequency band was significantly lower in Group L (p=0.013). Conclusion In the volumes and concentrations that were used in our study, levobupivacaine and bupivacaine created sensory blockade at the same level on average and did not reduce heart rate variability at the levels of these blockages. PMID:27366472