title: Effects of implantable cardioverter defibrillator implantation and shock application on biochemical markers of myocardial damage. Reduction in inappropriate therapy and mortality through ICD programming. Factors influencing appropriate firing of the implanted defibrillator for ventricular tachycardia/fibrillation: findings from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). Impact of atrial fibrillation on early complications and one year-survival after cardioverter defibrillator implantation: results from the German DEVICE registry. Quantitative Synthesis in Systematic Reviews Prognostic importance of defibrillator shocks in patients with heart failure. Association between atrial fibrillation and appropriate implantable cardioverter defibrillator therapy: results from a prospective study. Effect of long-detection interval vs standard-detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. Safety and efficacy of strategic implantable cardioverter-defibrillator programming to reduce the shock delivery burden in a primary prevention patient population. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. Comparison of benefit and mortality of implantable cardioverter-defibrillator therapy in patients aged ≥75 years versus those <75 years. Prognostic importance of atrial fibrillation in implantable cardioverter-defibrillator patients. Incidence of arrhythmias in a large cohort of patients with current implantable cardioverter-defibrillators in Spain: results from the UMBRELLA Registry. Mortality and appropriate and inappropriate therapy in patients with ischaemic heart disease and implanted cardioverter-defibrillators for primary prevention: data from the Danish ICD Register. Comparison between atrial fibrillation-triggered implantable cardioverter-defibrillator (ICD) shocks and inappropriate shocks caused by lead failure: different impact on prognosis in clinical practice.
abstract: BACKGROUND Implantable cardioverter defibrillator ( ICD ) implantation is a common approach in patients at high risk of sudden cardiac death . To check for normal function , it is necessary to test the ICD . For this purpose , repetitive induction and termination of ventricular fibrillation by direct current shocks is required . This may lead to minor myocardial damage . Cardiac troponin T ( cTnT ) and I ( cTnI ) are specific markers for the detection of myocardial injury . Because these proteins usually are undetectable in healthy individuals , they are excellent markers for detecting minimal myocardial damage . The objective of this study was to evaluate the effect of defibrillation of induced ventricular fibrillation on markers of myocardial damage . METHODS This study included 14 patients who underwent ICD implantation and intraoperative testing .  We measured cTnT , cTnI , creatine kinase MB ( CK-MB ) mass , CK activity , and myoglobin before and at definite times after intraoperative shock application . RESULTS Depending on the effectiveness of shocks and the energy applied , the cardiac-specific markers cTnT and cTnI , as well as CK-MB mass , showed a significant increase compared with the baseline value before testing and peaked for the most part 4 h after shock application . In contrast , the increases in CK activity and myoglobin were predominantly detectable in patients who received additional external shocks . CONCLUSIONS ICD implantation and testing leads to a short release of cardiac markers into the circulation . This release seems to be of cytoplasmic origin and depends on the number and effectiveness of the shocks applied BACKGROUND The implantable cardioverter-defibrillator ( ICD ) is highly effective in reducing mortality among patients at risk for fatal arrhythmias , but inappropriate ICD activations are frequent , with potential adverse effects . METHODS We r and omly assigned 1500 patients with a primary -prevention indication to receive an ICD with one of three programming configurations . The primary objective was to determine whether programmed high-rate therapy ( with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute ) or delayed therapy ( with a 60-second delay at 170 to 199 beats per minute , a 12-second delay at 200 to 249 beats per minute , and a 2.5-second delay at ≥250 beats per minute ) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks , as compared with conventional programming ( with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute ) . RESULTS During an average follow-up of 1.4 years , high-rate therapy and delayed ICD therapy , as compared with conventional device programming , were associated with reductions in a first occurrence of inappropriate therapy ( hazard ratio with high-rate therapy vs. conventional therapy , 0.21 ; 95 % confidence interval [ CI ] , 0.13 to 0.34 ; P<0.001 ; hazard ratio with delayed therapy vs. conventional therapy , 0.24 ; 95 % CI , 0.15 to 0.40 ; P<0.001 ) and reductions in all-cause mortality ( hazard ratio with high-rate therapy vs. conventional therapy , 0.45 ; 95 % CI , 0.24 to 0.85 ; P=0.01 ; hazard ratio with delayed therapy vs. conventional therapy , 0.56 ; 95 % CI , 0.30 to 1.02 ; P=0.06 ) . There were no significant differences in procedure-related adverse events among the three treatment groups . CONCLUSIONS Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher , as compared with conventional programming , was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up . ( Funded by Boston Scientific ; MADIT-RIT Clinical Trials.gov number , NCT00947310 . ) OBJECTIVES The purpose of this study was to prospect ively examine the role of clinical , laboratory , echocardiographic , and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator ( ICD ) therapy for ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) or death in the Multicenter Automatic Defibrillator Implantation Trial II ( MADIT-II ) population . BACKGROUND There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infa rct ion . METHODS We used secondary analysis in one arm of a multicenter r and omized clinical trial in patients with a previous myocardial infa rct ion and reduced left ventricular function . RESULTS We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study . Appropriate ICD therapy was observed in 169 subjects . Clinical , laboratory , echocardiographic , and electrophysiological variables , along with measures of clinical instability such as interim hospitalization for congestive heart failure ( IH-CHF ) and interim hospitalization for coronary events ( IH-CE ) , were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization . Interim hospitalization-CHF , IH-CE , no beta-blockers , digitalis use , blood urea nitrogen ( BUN ) > 25 , body mass index ( BMI ) > or = 30 kg/m2 , and New York Heart Association functional class > II were associated with increased risk for appropriate ICD therapy for VT , VF , or death . In a multivariate ( stepwise selection ) analysis , IH-CHF was associated with an increased risk for the end point of either VT or VF ( hazard ratio [ HR ] 2.52 , 95 % confidence interval [ CI ] 1.69 to 3.74 , p < 0.001 ) and for the combined end point of VT , VF , or death ( HR 2.97 , 95 % CI 2.15 to 4.09 , p < 0.001 ) . Interim hospitalization-CE was associated with an increased risk for VT , VF , or death ( HR 1.66 , 95 % CI 1.09 to 2.52 , p = 0.02 ) . CONCLUSIONS These results provide important mechanistic information , suggesting that worsening clinical condition and cardiac instability , as reflected by an IH-CHF or IH-CE , are subsequently associated with a significant increase in the risk for appropriate ICD therapy ( for VT/VF ) and death AIMS AND OBJECTIVE Outcome data of patients with implantable cardioverter defibrillators ( ICD ) and atrial fibrillation ( AF ) are conflicting . The German DEVICE registry aims to add further information on this particular cohort . METHODS AND RESULTS The German DEVICE registry is a nationwide prospect i ve multicenter data base of ICD implantations . 3261 patients are included ( 81 % males , 2701 ( 82.8 % ) first ICD implantations , 560 ( 17.2 % ) ICD replacements ) .  Cardiac resynchronization therapy ( CRT-D ) was performed in 882 patients ( 27.0 % ) . Sinus rhythm ( SR ) was present in 2654 ( 81.4 % ) and atrial fibrillation ( AF ) in 607 ( 18.6 % ) . Left ventricular ejection fraction ( LVEF ) did not differ between groups ( SR 32.3 % , AF 30.4 % ; p = 0.09 ) . AF patients were older ( AF 70.9 versus SR 63.9 years ; p < 0.0001 ) , presented with more co-morbidities ( diabetes , hypertension , chronic kidney disease ; all p < 0.001 ) . In-hospital complications were not significantly different between groups ( p = 0.58 ) . Follow-up information after one year was available in 2967 patients ( 91 % ) . One-year overall mortality after first ICD implantation was 4.9 % for SR and 11.2 % for AF patients ( p < 0.0001 ) ; mortality one year after ICD replacement was 8.4 % for SR and 12.0 % for AF ( p = 0.34 ) . No statistically significant difference between SR and AF patients receiving a CRT device was observed ( SR 6.9 % , AF 10.7 % , p = 0.16 ) in terms of one-year mortality . CONCLUSION The German DEVICE registry demonstrates that patients with AF who receive ICD devices are older , have more co-morbidity and more severe heart failure . AF carries an independent 1.39 fold risk ( 95 % CI 1.02 - 1.89 ) of death after one year in patients only with first ICD implantation A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis BACKGROUND Patients with heart failure who receive an implantable cardioverter-defibrillator ( ICD ) for primary prevention ( i.e. , prevention of a first life-threatening arrhythmic event ) may later receive therapeutic shocks from the ICD . Information about long-term prognosis after ICD therapy in such patients is limited . METHODS Of 829 patients with heart failure who were r and omly assigned to ICD therapy , we implanted the ICD in  811 . ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate . All other ICD shocks were considered to be inappropriate . RESULTS Over a median follow-up period of 45.5 months , 269 patients ( 33.2 % ) received at least one ICD shock , with 128 patients receiving only appropriate shocks , 87 receiving only inappropriate shocks , and 54 receiving both types of shock . In a Cox proportional-hazards model adjusted for baseline prognostic factors , an appropriate ICD shock , as compared with no appropriate shock , was associated with a significant increase in the subsequent risk of death from all causes ( hazard ratio , 5.68 ; 95 % confidence interval [ CI ] , 3.97 to 8.12 ; P<0.001 ) . An inappropriate ICD shock , as compared with no inappropriate shock , was also associated with a significant increase in the risk of death ( hazard ratio , 1.98 ; 95 % CI , 1.29 to 3.05 ; P=0.002 ) . For patients who survived longer than 24 hours after an appropriate ICD shock , the risk of death remained elevated ( hazard ratio , 2.99 ; 95 % CI , 2.04 to 4.37 ; P<0.001 ) . The most common cause of death among patients who received any ICD shock was progressive heart failure . CONCLUSIONS Among patients with heart failure in whom an ICD is implanted for primary prevention , those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks INTRODUCTION  Atrial fibrillation ( AF ) is associated with significant morbidity and mortality that may be related to hemodynamic impairment , thromboembolic events , or enhanced electrical instability of the ventricular myocardium . There is , however , a lack of data concerning the association of AF and ventricular tachyarrhythmias . METHODS AND RESULTS Consecutive patients with indication for an implantable cardioverter defibrillator ( ICD ) were classified for the presence or absence of persistent AF at the time of device implantation .  Incidence of device therapy , stored electrograms , and clinical events during follow-up were evaluated prospect ively . Two hundred fifty patients were included . During follow-up ( 20+/-14 months ) , patients in AF experienced appropriate device therapy for recurrent ventricular arrhythmias more frequently compared with patients in sinus rhythm ( SR ) ( 63 % vs 38 % , P = 0.01 ) . On multivariate analysis , AF was an independent predictor of appropriate ICD therapy ( relative risk 1.8 ; 95 % confidence interval [ CI ] 1.2 to 2.9 ) and inappropriate device therapy ( relative risk 2.3 ; 95 % CI 1.2 to 4.5 ) . Predefined clinical events ( cluster endpoint : death , syncope , and hospitalizations ) were observed more frequently in AF than in SR patients ( 55 % vs 31 % , P = 0.01 ) . Analysis of device-stored electrograms revealed a higher incidence of short-long-short cycles preceding ventricular arrhythmias in AF compared with SR patients ( 50 % vs 16 % , P = 0.002 ) . Baseline heart rate preceding ventricular arrhythmias did not differ between the two groups . CONCLUSION AF is an independent predictor of recurrent ventricular arrhythmias in ICD recipients . The underlying electrophysiologic mechanism seems to be irregular rather than rapid ventricular activation , with a high incidence of short-long-short sequences preceding ventricular tachyarrhythmias in AF patients IMPORTANCE Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary implantable cardioverter-defibrillator ( ICD ) therapies . OBJECTIVE To determine whether using 30 of 40 intervals to detect ventricular arrhythmias ( VT ) ( long detection ) during spontaneous fast VT episodes reduces antitachycardia pacing ( ATP ) and shock delivery more than 18 of 24 intervals ( st and ard detection ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , single-blind , parallel-group trial that enrolled 1902 primary and secondary prevention patients ( mean [ SD ] age , 65 [ 11 ] years ; 84 % men ; 75 % primary prevention ICD ) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers ( March 2008-December 2010 ) . INTERVENTIONS Patients were r and omized 1:1 to programming with long- ( n = 948 ) or st and ard-detection ( n = 954 ) intervals . MAIN OUTCOMES AND MEASURES Total number of ATPs and shocks delivered for all episodes ( primary outcomes ) and inappropriate shocks , mortality , and syncopal rate ( secondary outcomes ) . RESULTS During a median follow-up of 12 months ( interquartile range , 11 - 13 ) , long-detection group had 346 delivered therapies ( 42 therapies per 100 person-years , 95 % CI , 38 - 47 ) vs 557 in the st and ard-detection group ( 67 therapies per 100 person-years [ 95 % CI , 62 - 73 ] ; incident rate ratio [ IRR ] , 0.63 [ 95 % CI , 0.51 - 0.78 ] ; P < .001 ) . The long- vs the st and ard-detection group experienced 23 ATPs per 100 person-years ( 95 % CI , 20 - 27 ) vs 37 ATPs per 100 person-years ( 95 % CI , 33 - 41 ; IRR , 0.58 [ 95 % CI , 0.47 - 0.72 ] ; P < .001 ) ; 19 shocks per 100 person-years ( 95 % CI , 16 - 22 ) vs 30 shocks per 100 person-years ( 95 % CI , 26 - 34 ; IRR , 0.77 [ 95 % CI , 0.59 - 1.01 ] ; P = .06 ) , with a significant difference in the probability of therapy occurrence ( P < .001 ) ; and a reduction in first occurrence of inappropriate shock ( 5.1 per 100 patient-years [ 95 % CI , 3.7 - 6.9 ] vs 11.6 [ 95 % CI , 9.4 - 14.1 ] ; IRR , 0.55 [ 95 % CI , 0.36 - 0.85 ] ; P = .008 ) . Mortality ( 5.5 [ 95 % CI , 4.0 - 7.2 ] vs 6.3 [ 95 % CI , 4.8 - 8.2 ] per 100 patient-years ; HR , 0.87 ; P = .50 ) and arrhythmic syncope rates ( 3.1 [ 95 % CI , 2.6 - 4.6 ] vs 1.9 [ 95 % CI , 1.1 - 3.1 ] per 100 patient-years ; IRR , 1.60 [ 95 % CI , 0.76 - 3.41 ] ; P = .22 ) did not differ significantly between groups . CONCLUSIONS AND RELEVANCE Among patients receiving an ICD , the use of a long- vs st and ard-detection interval result ed in a lower rate of ATP and shocks , and inappropriate shocks . This programming strategy may be an appropriate alternative . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00617175 AIMS Strategically chosen ventricular tachycardia (VT)/ventricular fibrillation ( VF ) detection and therapy parameters aim ed at reducing shock deliveries were proven effective in studies that utilized single manufacturer devices with a follow-up of up to 1 year . Whether these beneficiary effects can be generalized to additional manufacturers and be maintained for longer periods is to be determined . Our aim was to evaluate the durability and applicability of the programming of strategic implantable cardioverter-defibrillators ( ICDs ) of various manufacturers , which is aim ed at reducing the shock delivery burden in primary prevention ICD recipients . METHODS AND RESULTS A retrospective analysis of prospect ively collected data of 300 ICD recipients of various manufacturers was conducted ; 160 devices were strategically programmed to reduce shocks and 140 were not . The primary endpoint was the composite of death and appropriate shocks . Additional outcomes were inappropriate shocks , syncope events , and non-sustained VTs . At a median follow-up of 24 months , 19 patients died , 31 received appropriate shocks , and 41 received inappropriate shocks . Multivariate analysis showed that strategic programming dedicated to shock reduction was associated with a 64 % risk reduction in the primary endpoint [ hazard ratio ( HR ) : 0.13 - 0.93 ; P = 0.03 ] and a 70 % reduction in inappropriate shock deliveries ( HR : 0.16 - 0.72 ; P = 0.01 ) . Very few syncope events occurred ( five patients , 1.6 % ) , and there was no between-group difference in this outcome . CONCLUSION Utilization of strategically chosen VT/VF detection and therapy parameters was found to be effective and safe in ICDs of various manufacturers at a median follow-up period of 2 years among primary prevention patients OBJECTIVE This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and , if so , whether the increase could be attributed to progressive heart failure or arrhythmic death . BACKGROUND Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias . The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure . METHODS A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline  for the risk of all-cause mortality , progressive pump-failure death and arrhythmic death . RESULTS The patients with atrial fibrillation at baseline , compared to those in sinus rhythm , had greater all-cause mortality ( 34 % vs. 23 % , p < 0.001 ) , death attributed to pump-failure ( 16.7 % vs. 9.4 % , p < 0.001 ) and were more likely to reach the composite end point of death or hospitalization for heart failure ( 45 % vs. 33 % , p < 0.001 ) , but there was no significant difference between the groups in arrhythmic deaths . After multivariate analysis , atrial fibrillation remained significantly associated with all-cause mortality ( relative risk [ RR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.62 , p=0.002 ) , progressive pump-failure death ( RR 1.42 , 95 % CI 1.09 to 1.85 , p=0.01 ) , the composite end point of death or hospitalization for heart failure ( RR 1.26 , 95 % CI 1.03 to 1.42 , p=0.02 ) , but not arrhythmic death ( RR 1.13 ; 95 % CI 0.75 to 1.71 ; p=0.55 ) . CONCLUSIONS The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality , largely explained by an increased risk for pump-failure death . These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction Implantable cardioverter-defibrillator ( ICD ) therapy decreases arrhythmic and all-cause mortality in patients at high risk of sudden death . However , its clinical benefit in elderly patients is uncertain . The aim of this study was to assess the long-term efficacy of ICD treatment in elderly patients and to identify markers of successful ICD therapy and risk factors of mortality . We performed multivariate analysis of a prospect i ve long-term data base from 2 tertiary care centers including 936 consecutive patients with an ICD . Predictors of ICD therapy and risk factors for mortality were assessed in patients ≥75 years old at ICD implantation compared to younger patients . Mean follow-up time was 43 ± 40 months . Rates of ICD therapy were similar in the 2 age groups . No significant predictors of ICD therapy could be identified in older patients . Median estimated survival was 132 months in patients < 75 years and 81 months in those ≥75 years old ( p = 0.006 ) . Decreased ejection fraction ( hazard ratio 1.62 per 10 % decrease , p = 0.03 ) and impaired renal function ( hazard ratio 1.57 per 10 ml/kg/m(2 ) decrease in estimated glomerular filtration rate , p = 0.02 ) were independent risk factors of mortality in patients ≥75 years old . However , mortality of older patients was similar to that of the age-matched general population irrespective of delivery of ICD therapy . In conclusion , ICD therapy is effective for treatment of life-threatening arrhythmias in all age groups . However , prevention of sudden cardiac death may have limited impact on overall mortality in older patients . Despite a similar rate of appropriate ICD therapies , risk of death is increased 1.6-fold in ICD recipients ≥75 years old compared to younger patients . Patients with decreased ejection fraction and impaired renal function are at highest risk OBJECTIVES This study aim ed to assess the prevalence of different types of  atrial fibrillation ( AF ) and their prognostic importance in  implantable cardioverter-defibrillator ( ICD ) patients . BACKGROUND The prevalence of AF has taken epidemic proportions in the population with cardiovascular disease . The prognostic importance of different types of AF in ICD patients remains unclear . METHODS Data on 913 consecutive patients ( 79 % men , mean age 62 + or - 13 years ) receiving an ICD at the Leiden University Medical Center were prospect ively collected . Among other characteristics , the existence and type of AF ( paroxysmal , persistent , or permanent ) were assessed at implantation . During follow-up , the occurrence of appropriate or inappropriate device therapy as well as mortality was noted . RESULTS At implantation , 73 % of patients had no history of AF , 9 % had a history of paroxysmal AF , 7 % had a history of persistent AF , and 11 % had permanent AF . During 833 + or - 394 days of follow-up , 117 ( 13 % ) patients died , 228 ( 25 % ) patients experienced appropriate device discharge , and 139 ( 15 % ) patients received inappropriate shocks . Patients with permanent AF exhibited more than double the risk of mortality , ventricular arrhythmias triggering device discharge , and inappropriate device therapy .  Patients with paroxysmal or persistent AF did not show a significant increased risk of mortality or appropriate device therapy but demonstrated almost 3 times the risk of inappropriate device therapy . CONCLUSIONS In the population currently receiving ICD treatment outside the setting of clinical trials , a large portion has either a history of AF or permanent AF . Both types of AF have prognostic implication s for mortality and appropriate as well as inappropriate device discharge AIMS The benefit of implantable cardioverter-defibrillators ( ICDs ) in patients at risk of sudden death has been established in r and omized clinical trials ( RCTs ) using the ICD models available at the time . However , observational large-scale data on the incidence of arrhythmias in up-to- date ICDs implanted according to the current guidelines are scarce . The aim was to assess the incidence of arrhythmias in a large , current ICD population based on a blinded peer review of the detected episodes . METHODS AND RESULTS UMBRELLA is a multicentre , observational registry of ICD patients followed by remote monitoring . Stored episodes were classified by a blinded committee of experts . Subgroup analyses were based on clinical profiles established by previous pivotal RCTs of ICDs . Of 1514 enrolled patients , 605 ( 39.9 % ) patients had 5951 episodes after 26 ± 17 months follow-up , being 3353 of them ( 56.3 % ) sustained ventricular arrhythmias ( SVA ) , and 13.2 % of SVA were self-terminated . Appropriate and inappropriate shocks occurred in 11.6 and 5 % of patients , respectively . The 3 years cumulative incidence of SVA was 25 % ( 95 % CI : 21 - 28 % ) in primary prevention patients and 41 % ( 95 % CI : 36 - 47 % ) in secondary prevention patients ( P < 0.001 ) . Male gender , secondary prevention , and atrial fibrillation as basal rhythm were significantly related to a higher incidence of SVA . CONCLUSION This real-world analysis suggests that  modern ICD patients have a low rate of appropriate and inappropriate shocks . The risk of SVA in secondary prevention patients is less than what has been reported in RCTs AIMS To evaluate the incidences of and risk factors predisposing to appropriate and inappropriate shocks and mortality in a ' real-world ' population of patients with ischaemic heart disease ( IHD ) and implantable cardioverter defibrillators ( ICD ) for primary prevention of sudden cardiac death ( SCD ) . METHODS AND RESULTS In this nationwide cohort , we prospect ively followed 1609 patients with IHD and left ventricular dysfunction from the Danish ICD Register who received an ICD for primary prevention of SCD ( 1 January 2007 to 30 November 2011 ) . Primary study outcomes were appropriate shocks , inappropriate shocks , and all-cause mortality . Secondary study outcomes included the composite endpoints : appropriate therapy and inappropriate therapy ( defined as shock or anti-tachycardia pacing ) . All-cause mortality was 12.1 % during a mean follow-up time of 1.9 ± 1.3 years . Inappropriate shocks and therapy occurred in 2.6 % and 3.7 % during follow-up , respectively . Appropriate shocks and therapy was identified in 7.8 % and 13.4 % , respectively . Time-dependent multivariable Cox regression analyses were used to identify risk factors of inappropriate/appropriate shock , therapy and mortality . Implantation of a dual-chamber ICD was associated with increased risk of both inappropriate shocks and any inappropriate therapy compared to single-chamber ICD [ hazard ratios ( HR ) = 2.45 ; confidence intervals (CI):1.16 - 5.14 and HR = 2.38 ; CI:1.28 - 4.42 , respectively ] . No excess risk of mortality was associated with any device type . CONCLUSION In this nationwide study of IHD patients with an ICD for primary prevention of SCD , the incidence of appropriate shocks as well as inappropriate shocks were significantly lower than reported in r and omized trials . Implantation of a dual-chamber ICD was associated with more inappropriate shocks compared with single chamber devices INTRODUCTION Recent studies suggest a worse impact of inappropriate shock therapies on the outcome of patients with an implantable cardioverter-defibrillator ( ICD ) .  However , it is not known whether the worse impact is attributed to the ICD shock itself or due to the underlying heart disease . The aim of the study was to evaluate the impact of inappropriate ICD shocks on clinical outcome by comparing ICD shocks triggered by atrial fibrillation ( AF ) with shocks caused by lead failure . METHODS AND RESULTS A total of 1,411 consecutive patients of the prospect i ve single-center ICD-registry Ludwigshafen who underwent an ICD implantation between 1992 and 2008 for primary or secondary prevention of sudden cardiac death were analyzed . During the median follow-up of 3 years , 297 ( 21 % ) patients experienced inappropriate ICD shocks . Sixty percent of patients had inappropriate shocks due to AF and 24 % due to lead defect or T-wave oversensing . Multiple ICD shocks ( ≥2 ) triggered by AF were associated with a worse prognosis , whereas a single shock due to AF or 1 or multiple shocks result ing from lead failure were not . ICD shocks caused by AF occurred more often in t and em with a serious adverse event than in patients with a lead failure ( 15 % vs 6 % , P < 0.05 ) . CONCLUSION Multiple ICD shocks triggered by AF are associated with a worse prognosis in ICD patients , whereas a single shock due to AF or shocks result ing from lead failure are not . These data support that the ICD shock itself has no worse impact on the outcome of ICD patients
target: Atrial fibrillation history is statistically significantly associated with adverse major clinical outcomes in ICD-implanted HF patients .
  Patients with AF have a higher risk of all-cause mortality , appropriate , and inappropriate ICD interventions compared with patients with no AF history .
background: AIMS To assess the association between atrial fibrillation ( AF ) and all-cause mortality and implantable cardioverter-defibrillators ( ICDs ) therapies  in heart failure ( HF ) patients with reduced ejection fraction and an ICD implanted .