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Background: Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations., Objective: This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD)., Methods: We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality., Results: Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m 2 vs 2.02 [1.89-2.16] m 2 ; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; P interaction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality., Conclusion: Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT)., Methods and Results: Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081)., Conclusion: In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present., Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271., (© 2023 European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials., Methods: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed., Results: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35)., Conclusion: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF)., Methods: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics., Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97)., Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF., (© 2023 Wiley Periodicals LLC.)

Background: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups., Methods: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death., Results: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; P interaction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death., Conclusions: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.

Background: Cardiac resynchronization therapy (CRT) has been demonstrated to improve heart failure (HF) symptoms, reverse LV remodeling, and reduce mortality and HF hospitalization (HFH) in patients with a reduced left ventricular (LV) ejection fraction (LVEF). Prior studies examining outcomes based on right ventricular (RV) lead position among CRT patients have provided mixed results. We performed a systematic review and meta-analysis of randomized controlled trials and prospective observational studies comparing RV apical (RVA) and non-apical (RVNA) lead position in CRT., Methods: Our meta-analysis was constructed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses. We searched EMBASE and MEDLINE. Eligible studies reported on at least one of the following outcomes of interest: all-cause mortality, the composite endpoint of death and first HFH hospitalization, change in LVEF, New York Heart Association (NYHA) class improvement, and change in LV end systolic volume (LVESV). We performed meta-analysis summaries using a DerSimonian-Laird random-effects model and conservatively used the Knapp-Hartung approach to adjust the standard errors of the estimated model coefficients., Results: We included nine studies representing a total of 1832 patients. Of those, 1318 (72%) patients had RVA lead placement and 514 (28%) had RVNA lead placement. The mean age of patients was 65.5 ± 4.4 years, and they were predominantly men (69%-97%). There was no statistically significant difference in all-cause mortality by RVA vs. RVNA (OR = 0.77, 95% CI 0.32-1.89; I 2 = 16.7%, p = 0.31), or in the combined endpoint of all-cause mortality and first HFH (OR 0.88, 95% CI 0.62-1.25; I 2 = 0%, p = 0.84). Also, there was no difference between RVA and RVNA for NYHA class improvement (OR = 1.03, 95% CI 0.9-1.17; I 2 = 0%, p = 0.99), change in LVEF (mean difference (MD) = 1.33, 95% CI -1.45 to 4.10; I 2 = 47%; p = 0.093), and change in LVESV (MD = -1.11, 95% CI -3.34 to 1.12; I 2 = 0%; p = 0.92)., Conclusion: This meta-analysis shows that in CRT pacing, RV lead position does not appear to be associated with clinical outcomes or LV reverse remodeling. Further studies should focus on the relationship of RV lead vis-à-vis LV lead location, and its clinical importance., Competing Interests: Declaration of Competing Interest D.P.M. has received research grants from Medtronic and Boston Scientific, consulting fees from Abbott, and speaking fees from Boston Scientific and Zoll. F.A.A: None. F.D: None. G.D·S: None. N.A.L: None. S.M.A. receives research, speaking and consulting fees from Medtronic, research and speaking fees from Abbott, and research fees from Boston Scientific. V.B: None., (Copyright © 2021. Published by Elsevier Inc.)

Background: Although cardiac resynchronization therapy (CRT) is effective for some patients with heart failure and a reduced left ventricular ejection fraction (HFrEF), evidence gaps remain for key clinical and policy areas. The objective of the study was to review the data on the effects of CRT for patients with HFrEF receiving pharmacological therapy alone or pharmacological therapy and an implantable cardioverter-defibrillator (ICD) and then, informed by a diverse group of stakeholders, to identify evidence gaps, prioritize them, and develop a research plan., Methods: Relevant studies were identified using PubMed and EMBASE and ongoing trials using clinicaltrials.gov. Forced-ranking prioritization method was applied by stakeholders to reach a consensus on the most important questions. Twenty-six stakeholders contributed to the expanded list of evidence gaps, including key investigators from existing randomized controlled trials and others representing different perspectives, including patients, the public, device manufacturers, and policymakers., Results: Of the 18 top-tier evidence gaps, 8 were related to specific populations or subgroups of interest. Seven were related to the comparative effectiveness and safety of CRT interventions or comparators, and 3 were related to the association of CRT treatment with specific outcomes. The association of comorbidities with CRT effectiveness ranked highest, followed by questions about the effectiveness of CRT among patients with atrial fibrillation and the relationship between gender, QRS morphology and duration, and outcomes for patients either with CRT plus ICD or with ICD., Conclusions: Evidence gaps presented in this article highlight numerous, important clinical and policy questions for which there is inconclusive evidence on the role of CRT and provide a framework for future collaborative research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: There is limited information on the outcomes after primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with heart failure (HF) and diabetes. This analysis evaluates the effectiveness of a strategy of ICD plus medical therapy vs. medical therapy alone among patients with HF and diabetes., Methods and Results: A patient-level combined-analysis was conducted from a combined dataset that included four primary prevention ICD trials of patients with HF or severely reduced ejection fractions: Multicenter Automatic Defibrillator Implantation Trial I (MADIT I), MADIT II, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE), and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In total, 3359 patients were included in the analysis. The primary outcome of interest was all-cause death. Compared with patients without diabetes (n = 2363), patients with diabetes (n = 996) were older and had a higher burden of cardiovascular risk factors. During a median follow-up of 2.6 years, 437 patients without diabetes died (178 with ICD vs. 259 without) and 280 patients with diabetes died (128 with ICD vs. 152 without). ICDs were associated with a reduced risk of all-cause mortality among patients without diabetes [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.67] but not among patients with diabetes (HR 0.88, 95% CI 0.7-1.12; interaction P = 0.015)., Conclusion: Among patients with HF and diabetes, primary prevention ICD in combination with medical therapy vs. medical therapy alone was not significantly associated with a reduced risk of all-cause death. Further studies are needed to evaluate the effectiveness of ICDs among patients with diabetes., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

The implantable cardioverter defibrillator (ICD) is a life-saving therapy in various patient populations. Although data on the outcomes of initial ICD implants are abundant, data on ICD replacements, especially in patients with improved left ventricular (LV) function, are scarce. Therefore, it is not known when it is safe to not replace an ICD that has reached the end of battery life. This article reviews data on patients with primary prevention ICDs who have improvement in left ventricular ejection fraction during follow-up and provides some guidance, based on the available evidence, related to circumstances when replacement of an ICD may be forgone., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD)., Methods: Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock. Clinical and demographic variables were included in a logistic regression model to predict appropriate shocks., Results: There were 1,463 patients randomized to an ICD, and 285 (19%) had ≥1 appropriate shock over a median follow-up of 2.59 years. Compared with patients without appropriate ICD shocks, patients who received any appropriate shock tended to have more severe heart failure. In a multiple logistic regression model, predictors of appropriate shocks included NYHA class (NYHA II vs. I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs. I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI 1.02-1.06), absence of beta-blocker therapy (OR 1.61, 95% CI 1.23-2.12), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45)., Conclusion: In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF, no beta-blocker therapy, and single chamber ICD (vs. dual chamber) were significant predictors of appropriate shocks., (© 2017 Wiley Periodicals, Inc.)

Background: Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death., Methods: We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian-Weibull survival regression models were used to assess the impact of NYHA class on the relationship between ICD use and mortality., Results: Of the 2,763 patients who met study criteria, 68% (n=1,867) were NYHA II and 52% (n=1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality (hazard ratio [HR] 0.65, 95% posterior credibility interval [PCI]) 0.40-0.99). The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction=.036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35-0.85), and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48-1.24), although this was not statistically significant., Conclusions: Primary prevention ICDs reduce mortality in NYHA class II patients and trend toward reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: Conflicting data have emerged on the efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (primary prevention ICDs) in patients with nonischemic cardiomyopathy., Objective: To investigate the association of primary prevention ICDs with all-cause mortality in patients with nonischemic cardiomyopathy., Data Sources: PubMed was searched from January 1, 2000, through October 31, 2016, for the terms implantable defibrillator OR implantable cardioverter defibrillator AND non-ischemic cardiomyopathy. Additional references were identified from bibliographies of pertinent articles and queries to experts in this field., Study Selection: Inclusion criteria consisted of a randomized clinical trial design and comparison of the ICD with medical therapy (control) in at least 100 patients with nonischemic cardiomyopathy. In addition, studies had to report on all-cause mortality during a follow-up period of at least 12 months and be published in English. The search yielded 10 studies, of which only 1 met the inclusion criteria. A search of bibliographies of pertinent articles and queries of experts in this field led to 3 additional studies., Data Extraction and Synthesis: The PRISMA guidelines were used to abstract data and assess data quality and validity. Data were pooled using fixed- and random-effects models., Main Outcomes and Measures: The primary end point was all-cause mortality. Before data collection started, primary prevention ICDs were hypothesized to reduce all-cause mortality among patients with nonischemic cardiomyopathy., Results: Four randomized clinical trials met the selection criteria and included 1874 unique patients; 937 were in the ICD group and 937 in the control group. Pooling data from these trials showed a significant reduction in all-cause mortality with an ICD (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008; P = .87 for heterogeneity)., Conclusions and Relevance: Primary prevention ICDs are efficacious at reducing all-cause mortality among patients with nonischemic cardiomyopathy. These findings support professional guidelines that recommend the use of ICDs in such patients.

Background: Clinical trials of implantable cardioverter defibrillators (ICDs) for primary prevention enrolled a limited number of women. We sought to examine clinical practice data to compare survival rates among women with heart failure with or without a primary prevention ICD., Methods and Results: We linked data from 264 US hospitals included in the Get With The Guidelines for Heart Failure registry with data from the Centers for Medicare and Medicaid Services. From these sources, we propensity score matched 430 women with heart failure who received a primary prevention ICD to 430 women who did not; we further adjusted using a Cox proportional hazards model. Median follow-up was 3.4 and 3.0 years. For comparison, we matched 859 men receiving an ICD with 859 who did not; median follow-up was 3.9 versus 2.9 years. In the matched cohorts, an ICD was associated with similarly better survival in women (hazard ratio, 0.78; 95% confidence interval, 0.66-0.92; P=0.003) and men (hazard ratio, 0.76; 95% confidence interval, 0.67-0.87 P<0.001). There was no interaction between sex and presence of an ICD with respect to survival (P=0.79)., Conclusions: Among patients with heart failure with reduced left ventricular ejection fraction, a primary prevention ICD was associated with a significant survival advantage among women and among men. These findings support guideline-directed use of primary prevention ICDs in eligible patients., (© 2015 American Heart Association, Inc.)

Background: Sudden cardiac death is the leading cause of death among end-stage kidney disease patients (ESKD) on dialysis, but the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in this population is uncertain. We conducted this investigation to compare the mortality of dialysis patients receiving a primary prevention ICD with matched controls., Methods: We used data from the National Cardiovascular Data Registry's ICD Registry to select dialysis patients who received a primary prevention ICD, and the Get with the Guidelines-Heart Failure Registry to select a comparator cohort. We matched ICD recipients and no-ICD patients using propensity score techniques to reduce confounding, and overall survival was compared between groups., Results: We identified 108 dialysis patients receiving primary prevention ICDs and 195 comparable dialysis patients without ICDs. One year (3-year) mortality was 42.2% (68.8%) in the ICD registry cohort compared with 38.1% (75.7%) in the control cohort. There was no significant survival advantage associated with ICD [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.66-1.13, log-rank P = 0.29]. After propensity matching, our analysis included 86 ICD patients and 86 matched controls. Comparing the propensity-matched cohorts, 1 year (3 years) mortality was 43.4% (74.0%) in the ICD cohort and 39.7% (76.6%) in the control cohort; there was no significant difference in mortality outcome between groups (HR = 0.94, 95% CI: 0.67-1.31, log-rank P = 0.71)., Conclusions: We did not observe a significant association between primary prevention ICDs and reduced mortality among ESKD patients receiving dialysis. Consideration of the potential risks and benefits of ICD implantation in these patients should be undertaken while awaiting the results of definitive clinical trials., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objectives: The purpose of this study was to assess the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in women., Background: Clinical trials of primary prevention ICDs enrolled a limited number of women., Methods: Using a propensity score method, we matched 490 women ≥65 years of age who received an ICD during a hospitalization for heart failure in the National Cardiovascular Data Registry ICD Registry from January 1, 2006, through December 31, 2007, to 490 ICD-eligible women without an ICD hospitalized for heart failure in the Get With The Guidelines for Heart Failure database from January 1, 2006, through December 31, 2009. The primary endpoint was all-cause mortality obtained from the Medicare Claims Database. An identical analysis was conducted in men., Results: Median follow-up for patients with an ICD was 4.6 years versus 3.2 years for patients with no ICD. Compared with women with no ICD, those with an ICD were younger and less frequently white. In the matched cohorts, the survival of women with an ICD was significantly longer than that of women without an ICD (adjusted hazard ratio: 0.79, 95% confidence interval: 0.66 to 0.95; p = 0.013). Similarly, men with an ICD had longer survival than men without an ICD (adjusted hazard ratio: 0.73, 95% confidence interval: 0.65 to 0.83; p < 0.0001). There was no interaction between sex and the presence of an ICD with respect to survival (p = 0.44)., Conclusions: Among older women with left ventricular dysfunction, a primary prevention ICD was associated with a significant survival benefit that was nearly identical to that seen in men. These findings support the use of primary prevention ICDs in eligible patients regardless of sex., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine if the benefit of implantable cardioverter-defibrillators (ICDs) is modulated by medical comorbidity., Background: Primary prevention ICDs improve survival in patients at risk for sudden cardiac death. Their benefit in patients with significant comorbid illness has not been demonstrated., Methods: Original, patient-level datasets from MADIT I (Multicenter Automatic Defibrillator Implantation Trial I), MADIT II, DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation), and SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were combined. Patients in the combined population (N = 3,348) were assessed with respect to the following comorbidities: smoking, pulmonary disease, diabetes, peripheral vascular disease, atrial fibrillation, ischemic heart disease, and chronic kidney disease. The primary outcome was overall mortality, using the hazard ratio (HR) of time to death for patients receiving an ICD versus no ICD by extent of medical comorbidity, and adjusted for age, sex, race, left ventricular ejection fraction, use of antiarrhythmic drugs, beta-blockers, and angiotensin-converting enzyme inhibitors., Results: Overall, 25% of patients (n = 830) had <2 comorbid conditions versus 75% (n = 2,518) with significant comorbidity (≥2). The unadjusted hazard of death for patients with an ICD versus no ICD was significantly lower, but this effect was less for patients with ≥2 comorbidities (unadjusted HR: 0.71; 95% confidence interval: 0.61 to 0.84) compared with those with <2 comorbidities (unadjusted HR: 0.59; 95% confidence interval: 0.40 to 0.87). After adjustment, the benefit of an ICD decreased with increasing number of comorbidities (p = 0.004)., Conclusions: Patients with extensive comorbid medical illnesses may experience less benefit from primary prevention ICDs than those with less comorbidity; implantation should be carefully considered in sick patients. Further study of ICDs in medically complex patients is warranted., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD)., Methods and Results: Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26,056), those with CKD (n=21,226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99-2.18; P<0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92-4.50; P<0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46-5.17; P<0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction., Conclusions: The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy., (© 2014 American Heart Association, Inc.)

Importance: Clinical trials of prophylactic implantable cardioverter-defibrillators (ICDs) have included a minority of patients with a left ventricular ejection fraction (LVEF) between 30% and 35%. Because a large number of ICDs in the United States are implanted in such patients, it is important to study survival associated with this therapy., Objective: To characterize patients with LVEF between 30% and 35% and compare the survival of those with and without ICDs., Design, Setting, and Participants: Retrospective cohort study of Medicare beneficiaries in the National Cardiovascular Data Registry ICD registry (January 1, 2006, through December 31, 2007) with an LVEF between 30% and 35% who received an ICD during a heart failure hospitalization and similar patients in the Get With The Guidelines-Heart Failure (GWTG-HF) database (January 1, 2005, through December 31, 2009) with no ICD. The analysis was repeated in patients with an LVEF less than 30%. There were 3120 patients with an LVEF between 30% and 35% (816 in matched cohorts) and 4578 with an LVEF less than 30% (2176 in matched cohorts). Propensity score matching and Cox models were applied., Main Outcomes and Measures: The primary outcome was all-cause mortality; data were obtained from Medicare claims through December 31, 2011., Results: There were no significant differences in the baseline characteristics of the matched groups (n = 408 for both groups). Among patients with an LVEF between 30% and 35%, there were 248 deaths in the ICD Registry group, within a median follow-up of 4.4 years (interquartile range, 2.7-4.9) and 249 deaths in the GWTG HF group, within a median follow-up of 2.9 years (interquartile range, 2.1-4.4). The risk of all-cause mortality in patients with an LVEF between 30% and 35% and an ICD was significantly lower than that in matched patients without an ICD (3-year mortality rates: 51.4% vs 55.0%; hazard ratio, 0.83 [95% CI, 0.69-0.99]; P = .04). Presence of an ICD also was associated with better survival in patients with an LVEF less than 30% (3-year mortality rates: 45.0% vs 57.6%; 634 and 660 total deaths; hazard ratio, 0.72 [95% CI, 0.65-0.81]; P < .001) (P = .20 for interaction)., Conclusions and Relevance: Among Medicare beneficiaries hospitalized for heart failure and with an LVEF between 30% and 35% and less than 30%, survival at 3 years was better in patients who received a prophylactic ICD than in comparable patients with no ICD. These findings support guideline recommendations to implant prophylactic ICDs in eligible patients with an LVEF of 35% or less.

Background: Several studies based on claims data have reported underutilization of evidence-based heart failure (HF) therapies. The degree to which these estimates fail to account for therapeutic contraindications is unclear., Methods: We identified patients with HF and left ventricular ejection fraction ≤45% seen between January 1, 2010, and July 1, 2010, at a tertiary care Veterans Affairs Medical Center. Medical records were abstracted to evaluate utilization of and contraindications to β-blocker, angiotensin-converting enzyme inhibitor, aldosterone antagonist, anticoagulation for atrial fibrillation, implantable cardioverter-defibrillator, and cardiac resynchronization therapies., Results: Of the 178 patients with HF and an ejection fraction ≤45%, 78 (44%) received every guideline-recommended therapy. After accounting for medical contraindications, 77 (72%) of 107 patients received every guideline-recommended therapy. Adherence to recommendations for β-blocker (98%), angiotensin-converting enzyme inhibitor/angiotensin blocker (95%), and anticoagulation (97%) were better than adherence to implantable cardioverter-defibrillator (82%), cardiac resynchronization therapy (59%), or aldosterone antagonist (51%) recommendations. In adjusted analysis, lower New York Heart Association functional class and care by a cardiologist were associated with improved guideline adherence (P < .001)., Conclusions: Many patients with HF have therapeutic contraindications, and a failure to account for these may lead to a large underestimation of the true guideline adherence rates., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Context: Practice guidelines do not recommend use of an implantable cardioverter-defibrillator (ICD) for primary prevention in patients recovering from a myocardial infarction or coronary artery bypass graft surgery and those with severe heart failure symptoms or a recent diagnosis of heart failure., Objective: To determine the number, characteristics, and in-hospital outcomes of patients who receive a non-evidence-based ICD and examine the distribution of these implants by site, physician specialty, and year of procedure., Design, Setting, and Patients: Retrospective cohort study of cases submitted to the National Cardiovascular Data Registry-ICD Registry between January 1, 2006, and June 30, 2009., Main Outcome Measure: In-hospital outcomes., Results: Of 111,707 patients, 25,145 received non-evidence-based ICD implants (22.5%). Patients who received a non-evidence-based ICD compared with those who received an evidence-based ICD had a significantly higher risk of in-hospital death (0.57% [95% confidence interval {CI}, 0.48%-0.66%] vs 0.18% [95% CI, 0.15%-0.20%]; P <.001) and any postprocedure complication (3.23% [95% CI, 3.01%-3.45%] vs 2.41% [95% CI, 2.31%-2.51%]; P <.001). There was substantial variation in non-evidence-based ICDs by site. The rate of non-evidence-based ICD implants was significantly lower for electrophysiologists (20.8%; 95% CI, 20.5%-21.1%) than nonelectrophysiologists (24.8% [95% CI, 24.2%-25.3%] for nonelectrophysiologist cardiologists; 36.1% [95% CI, 34.3%-38.0%] for thoracic surgeons; and 24.9% [95% CI, 23.8%-25.9%] for other specialties) (P<.001 for all comparisons). There was no clear decrease in the rate of non-evidence-based ICDs over time (24.5% [6908/28,233] in 2006, 21.8% [7395/33,965] in 2007, 22.0% [7245/32,960] in 2008, and 21.7% [3597/16,549] in 2009; P <.001 for trend from 2006-2009 and P = .94 for trend from 2007-2009)., Conclusion: Among patients with ICD implants in this registry, 22.5% did not meet evidence-based criteria for implantation.

Background: Implantable cardioverter defibrillator (ICD) therapy improves survival of patients with systolic heart failure. We assessed whether physicians' recommendation for ICD therapy varies as a function of patient age, gender, race, and physician's specialty., Methods: We surveyed a random sample (n = 9969) of U.S. physicians who are active members of the American College of Cardiology (ACC). We asked participants about their likelihood to recommend ICD therapy in 4 clinical scenarios that randomly varied patient age, gender, race, and ICD indication (guideline Class I, Class IIa, Class III, and Class I in a noncompliant patient)., Results: Responses were received from 1210 physicians (response rate 12%), of whom 1127 met the study inclusion criteria. Responders and nonresponders had similar demographics. In responding to hypothetical clinical scenarios, physicians were less likely to recommend an ICD to older patients (≥80 vs 50 years) (P < 0.01) but were unaffected by gender or race for all class indications. Compared with non-electrophysiologists (EPs), EPs were significantly more likely to recommend an ICD for a Class I indication (92.4% vs 81.4%; P < 0.01), but they were not more likely to offer an ICD for a Class III indication (0.4% vs 0.6%; P = 0.95)., Conclusions: Based on survey responses, physicians were equally willing to offer an ICD to men and women and to whites and blacks, but were less likely to offer an ICD to an older patient even when indicated by practice guidelines. Electrophysiologists (EPs) more often adhered to practice guideline recommendations on ICD therapy compared with non-EPs., (©2011, Wiley Periodicals, Inc.)

Background: More than 80% of sudden cardiac deaths (SCDs) occur in patients >or=65 years old; the cost-effectiveness of implantable cardioverter defibrillator (ICD) therapy in older patients remains unclear. We sought to examine the cost-effectiveness of ICD therapy in at-risk patients >or=65 years old., Methods: We developed a Markov model to evaluate lifetime costs and benefits of ICD therapy compared with optimal medical therapy in patients >or=65 years of age with left ventricular dysfunction. Data were derived from the literature and existing clinical trials of primary prevention of SCD. Outcome measures included life years, quality-adjusted life years, costs, and incremental cost-effectiveness., Results: Benefits and costs of ICD therapy in older individuals varied widely by clinical-trial population. In the 5 trials considered, for patients >or=65 years of age, ICDs demonstrated a life expectancy benefit compared with control therapy (incremental cost-effectiveness ratios ranging from $37,031-$138,458 per quality-adjusted life year). For 75-year-old patients, the findings were qualitatively similar, although cost-effectiveness was reduced in all trial populations. In sensitivity analyses, cost-effectiveness of ICD therapy in older individuals depended upon the trial population, quality of life, device cost, and frequency of generator replacement. Sensitivity analyses on other variables did not change the results substantially., Conclusions: The cost-effectiveness of ICD therapy for primary prevention in older patients varies widely among trials. Given an aging US population and the high risk of SCD in these individuals, further studies of ICD therapy and their cost-effectiveness-specifically in older patients-are needed., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Whether there is an optimal time to place an implantable cardioverter-defibrillator (ICD) more than 40 days after myocardial infarction (MI) in guideline-eligible patients is unknown. Objective: To evaluate the effect of time from MI to randomization on mortality, rehospitalizations, and complications. Methods: Individual data on patients enrolled in 9 primary prevention ICD trials were provided. Clinical trials were eligible for the current analysis if they enrolled patients with an MI more than 40 days prior to randomization to primary prevention ICD therapy vs usual care: Multicenter Automatic Defibrillator Implantation Trial I, Multicenter UnSustained Tachyardia Trial, Multicenter Automatic Defibrillator Implantation Trial II, and Sudden Cardiac Death in Heart Failure Trial. Results: ICD recipients died less frequently than nonrecipients at 5 years across all subgroups of time from MI to randomization. In unadjusted Cox proportional hazards regression, a survival benefit was evident in most subgroups. Adjusted Bayesian Weibull survival modeling yielded hazard ratio (HR) 0.50, 95% posterior credible interval (PCI) 0.20–1.25 41–180 days after MI; HR 0.98, 95% PCI 0.37–2.37 181–365 days after MI; HR 0.22, 95% PCI 0.07–0.59>1–2 years after MI; HR 0.42, 95% PCI 0.17–0.90>2–5 years after MI; HR 0.55, 95% PCI 0.25–1.15>5–10 years after MI; and HR 0.48, 95% PCI 0.20–1.02>10 years after MI. There was no evidence of an interaction between time from MI and all-cause mortality, rehospitalizations, or complications. Conclusions: In this meta-analysis, there was scant evidence that the efficacy of primary prevention ICD therapy depends on time to implantation more than 40 days after MI. Similarly, there was no evidence that the risks of rehospitalizations or complications depend on time more than 40 days after MI. [Copyright &y& Elsevier]

The article is a study that evaluates the quality of patient education and decision-making materials related to sudden cardiac arrest (SCA) and treatment with implantable cardioverter defibrillators (ICDs). The 18 SCA and ICD educational tools were assessed by a panel of two cardiologists, two electrophysiologists, a psychologist, a patient advocate, and a health services researcher. Four of the tools were rated good, 12 were marginal, and two were inadequate.

Abstract: Introduction: This study was designed to determine if physicians’ attitudes and recommendations surrounding implantable cardioverter-defibrillators (ICDs) are regionally associated with ICD use. Methods and Results: A national sample of 9969 members of the American College of Cardiology was surveyed electronically. Responses were merged with rates of ICD implantation from the National Cardiovascular Data Registry. Multivariable regression was used to assess trends between regional use and responses. We received 1210 responses (12%) and used 1124 after exclusions. Across regions, physicians were equally likely to recommend ICDs to males or females with ischemic (∼99% for both; P = NS) or nonischemic cardiomyopathy (85 vs. 88% P = 0.85). Significant increasing trends in the probability recommending ICD therapy were found when the patient was “frail” (21% to 32%; P = .03) or had a life expectancy <1 year (5% to 10%; P = .05). These differences were not associated with attitudes toward ICDs. Conclusions: Independent of variations in physicians’ attitudes towards ICDs, physicians in regions of low ICD use are not less likely to recommend ICDs in situations clearly supported by guidelines while those in regions of high ICD use are more likely to recommend ICDs to patients who might have limited benefit. [Copyright &y& Elsevier]

ICD: Remote Monitoring Versus Clinic Interrogations. Introduction: Remote monitoring is increasingly becoming the new standard of care for implantable cardioverter defibrillator (ICD) follow-up. We sought to determine whether remote monitoring of ICDs improves patient outcomes compared with quarterly device interrogations in clinic. Methods and Results: In this single-center pilot clinical trial, adult patients with an ICD were randomly assigned to remote monitoring versus quarterly device interrogations in clinic. The primary endpoint was a composite of cardiovascular hospitalization, emergency room visit for a cardiac cause, and unscheduled visit to the electrophysiology clinic for a device-related issue at 1 year. We also examined health-related quality of life, costs, and patient satisfaction with their ICD care. Of 151 patients enrolled in this trial, 76 were randomized to remote monitoring and 75 to quarterly device interrogations in clinic. There was no significant difference in the primary endpoint (32% in the remote monitoring arm vs 34% in the control arm; P = 0.8), mortality, or cost between the 2 arms. Quality of life and patient satisfaction were significantly better in the control arm than in the remote monitoring arm at 6 months (83 [25th, 75th percentiles 70, 90] vs 75 [50, 85]; P = 0.002 and 88 [75, 100] vs 75 [75, 88]; P = 0.03, respectively), but not at 12 months. Conclusion: We showed no significant reduction in cardiac-related resource utilization with remote monitoring of ICDs. However, given the small number of patients in our study, the real clinical and health economics impact of remote monitoring needs to be verified by a large, multicenter, randomized clinical trial. (J Cardiovasc Electrophysiol, Vol. 21, pp. 545-550, May 2010) [ABSTRACT FROM AUTHOR]

Background: Many patients in the SCD-HeFT had a significant improvement in the left ventricular ejection fraction (LVEF) during the course of the study, but factors and outcomes associated with such improvement are uncertain. Objective: We examined factors and outcomes associated with a 10% improvement in LVEF by analyzing patients in the SCD-HeFT who were randomized to placebo or an ICD and who had their LVEF checked during follow-up (n=837). Methods: To examine all-cause mortality, we used joint longitudinal-survival models. We defined the longitudinal model as a linear mixed-effects model for the log-transformed LVEF regressed on time since randomization. Time-to-event was modeled by Cox proportional hazards models. Similarly, competing risk joint models were fitted to cause-specific mortality. Results: During a median follow-up of 3.99 years, 276 patients (33%; 149 had an ICD) had a significant improvement in LVEF and 561 (67%; of whom 267 had an ICD) had no significant change in LVEF. Factors significantly associated with an LVEF improvement included male gender (p = 0.001), white race (p < 0.001), history of hypertension (p < 0.001), a QRS duration <120 ms (p < 0.001), and beta blocker use (p=0.01). Improvement in LVEF was associated with a significant improvement in survival (HR 0.87, 95% CI 0.82 - 0.92; see figure) and decreased rates of both non-arrhythmic cardiac death (HR 0.83, 95% CI 0.76-0.90) and arrhythmic cardiac death (HR 0.86, 95% CI 0.77-0.97). Furthermore, an ICD was associated with improved survival (HR 0.63, 95% CI 0.42-0.95). Conclusion: About a third of patients randomized to placebo or an ICD in SCD-HeFT had a significant improvement in LVEF during follow-up. Improvement in LVEF is associated with both survival benefit and decreased rates of arrhythmic and non-arrhythmic cardiac death. [ABSTRACT FROM AUTHOR]