Search

Background: There are limited data on the prognostic implications of brain natriuretic peptide (BNP) assessment in patients with mildly symptomatic heart failure (HF) who receive cardiac resynchronization therapy with a defibrillator (CRT-D)., Methods and Results: The effect of elevated baseline and 1-year BNP levels (dichotomized at the upper tertile BNP of 120 pg/mL) on the risk of HF or death was assessed among the cohort of 1197 patients with baseline BNP data enrolled in MADIT (Multicenter Automated Defibrillator Implantation Trial)-CRT. Elevated baseline BNP was associated with a significant 68% (P=0.007) and 58% (P=0.02) increase in the risk of HF or death among MADIT-CRT patients allocated to CRT-D and implantable cardioverter defibrillator-only therapy, respectively. At 1 year of follow-up, patients allocated to CRT-D displayed significantly greater reductions in BNP (26% reduction) levels compared with implantable cardioverter defibrillator-only patients (8% increase; P=0.005). Patients with CRT-D in whom 1-year BNP levels were reduced or remained low experienced a significantly lower risk of subsequent HF or death as compared with patients in whom 1-year BNP levels were high. Similarly, the echocardiographic response to CRT-D was highest among those who maintained low BNP levels or in whom BNP level at 1-year was reduced., Conclusions: Our findings suggest that assessment of baseline and follow-up BNP provides important prognostic implications in patients with mildly symptomatic HF who receive CRT.

Background: Right ventricular function (RVF) is an important determinant of outcome in patients with heart failure, and those with severe RV dysfunction have worse outcome after cardiac resynchronization therapy (CRT). We used data from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) Trial to determine whether therapy with CRT is influenced by or affects RV function and to define the relationship between RV function and outcomes., Methods and Results: A total of 1820 patients were randomly assigned to CRT plus implantable cardioverter defibrillator or implantable cardioverter defibrillator-only in a 3:2 ratio. We assessed RVF as RV fractional area change by echocardiography at baseline and after 1 year of therapy (n=1511 and 1273, respectively). The median RV fractional area change was 41%, with 10.9% of patients <35% at baseline. Baseline RVF did not modify the treatment effect of CRT on the primary outcome (interaction P=0.19). Randomization to CRT-implantable cardioverter defibrillator was associated with a greater improvement in RVF (ΔRV fractional area change 8.1% versus 5.4%; P<0.001), and improvement in RVF was related to subsequent outcomes. Every 5-point increase in RV fractional area change was associated with a 22% reduction in event rates (hazard ratio, 0.78; 95% confidence interval, 0.66-0.92; P=0.003), although this was not independent of the concurrent improvement in left ventricular function. Baseline tricuspid regurgitant velocity, a measure of pulmonary systolic pressure, was predictive of events in a multivariate analysis (hazard ratio, 1.86; 95% confidence interval, 1.24-2.8; P=0.003)., Conclusions: In this population with mild heart failure symptoms, CRT was associated with improvement in RVF, which improved in parallel with improvement in left ventricular function. Patients with the best RVF at 1 year demonstrated the lowest subsequent event rates., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01294449.

Importance: Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown., Objective: To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n = 742) and SCD-HeFT (n = 829)., Design, Setting, and Patients: Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score-matched patients) or the SCD-HeFT criteria (3352 propensity score-matched patients). Mortality data for the registry patients were collected through December 31, 2009., Main Outcome Measures: Cox proportional hazards models were used to compare mortality from any cause., Results: The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II-like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85-1.31; P = .62). Likewise, the survival among SCD-HeFT-like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97-1.38; P = .11)., Conclusions and Relevance: There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice., Trial Registration: clinicaltrials.gov Identifier: NCT00000609.

Objectives: This study compared the quality of life (QOL) of patients with cardiac resynchronization therapy (CRT) and an implantable cardioverter-defibrillator (ICD) to patients with an ICD only., Background: CRT with ICD is associated with a reduction in heart failure risk among minimally symptomatic patients. It is unknown whether this improves QOL., Methods: This study uses the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) data. The MADIT-CRT enrolled 1,820 patients at 110 centers across 14 countries. Patients had ischemic cardiomyopathy (New York Heart Association [NYHA] functional class I or II) or nonischemic cardiomyopathy (NYHA functional class II only), sinus rhythm, an ejection fraction of 30% or less, and prolonged intraventricular conduction with a QRS duration of 130 ms or more. QOL was evaluated on the 1,699 patients with baseline and follow-up measures using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Six dimensions (Physical Limitation, Symptom Stability, Symptom Frequency, Symptom Burden, Quality of Life, and Social Limitations) and 3 summary scores (Total Symptom, Clinical Summary, and Overall Summary) were analyzed., Results: During an average follow-up of 2.4 years, the CRT-ICD group had greater improvement than the ICD-only group on all KCCQ measures (p < 0.05 on each scale). These differences were significant among patients with left bundle branch block conduction disturbance (n = 1,204, p < 0.01 on each scale), but not among patients without left bundle branch block (n = 494)., Conclusions: Compared with patients with ICD only, CRT-ICD is associated with greater improvement in QOL among relatively asymptomatic patients, specifically among those with left bundle branch conduction disturbance., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device., Methods and Results: The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS ≥150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume ≥125 mL/m(2), and left atrial volume <40 mL/m(2)). Multivariate analysis showed a 13% (P<0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0-14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratio=0.87; P=0.52); patients in the second and third quartiles derived 33% (P=0.04) and 36% (P=0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% (P<0.001) risk reduction (P for trend=0.005)., Conclusion: Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Objectives: The evaluation of the risk of recurring heart failure events (HFEs) was a pre-specified substudy of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy)., Background: There are limited data regarding the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the occurrence of recurring heart failure episodes after a first post-implantation HFE., Methods: Data with regard to recurring HFEs were prospectively collected for all 1,820 MADIT-CRT participants. The CRT-D versus defibrillator-only risk for nonfatal first- and subsequent-HFEs was assessed by Cox proportional hazards and Andersen-Gill proportional intensity regression modeling, respectively, in efficacy analyses recognizing active device-type during follow-up., Results: Multivariate analysis showed that CRT-D was associated with a significant reduction in the risk of a first HFE (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44 to 0.67, p < 0.001) and with a similar magnitude of reduction in the risk of HFEs subsequent to a first post-enrollment event (HR: 0.62, 95% CI: 0.45 to 0.85, p = 0.003). The benefit of CRT-D for the prevention of first and subsequent HFEs was pronounced among patients with left bundle branch block (HR: 0.38, 95% CI: 0.29 to 0.49, p < 0.001; and HR: 0.50, 95% CI: 0.33 to 0.76, p = 0.001, respectively) and nonsignificant in non-left bundle branch block patients (HR: 1.12, 95% CI: 0.77 to 1.64, p = 0.55; and HR: 0.99, 95% CI: 0.58 to 1.69, p = 0.96, respectively; p values for interaction: p < 0.001 and p = 0.06, respectively). The occurrences of first and second HFEs were associated with 7- and nearly 19-fold respective increases in the risk of subsequent mortality., Conclusions: In the MADIT-CRT trial, the benefit of cardiac resynchronization therapy for the reduction in recurring HFEs was maintained after the occurrence of a first post-enrollment event. The occurrence of HFEs greatly increased the risk of death. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac remodelling is a progressive process after myocardial infarction (MI). However, currently there are no data regarding the effect of s:elapsed time from MI on the benefit of cardiac resynchronization therapy with defibrillator (CRT-D). The present study was designed to evaluate the relationship between elapsed time from MI and the benefit of preventive CRT-D therapy in patients with ischaemic cardiomyopathy (ICM)., Methods and Results: The risk of heart failure (HF) or death as a function of elapsed time from MI to enrolment, by treatment with CRT-D vs. implantable cardioverter defibrillator (ICD)-only therapy, was assessed among 704 ICM patients with a documented MI enrolled in MADIT-CRT, and separately in a subset of ICM patients without a documented prior MI (n = 237). In ICD patients, the adjusted risk of HF or death increased by 4% (P = 0.01) for each year elapsed from MI. Multivariate analysis demonstrated that patients with remote MI [categorized at the median value (≥8 years)] derived a significantly greater benefit from CRT-D [HR = 0.42 (P < 0.001)] than those with a more recent MI [HR = 1.26 (P = 0.35); P-value for interaction <0.001]. Consistently, the benefit of CRT-D was directly related to increasing quartiles of elapsed time from MI [Q(1) (<3 years): HR = 1.67; P = 0.20, Q(2) (3-8 years): HR = 1.12; P = 0.71, Q(3) (8-15 years): HR = 0.47; P = 0.02, and Q(4) (≥15 years): HR = 0.38; P = 0.001]. The ICM subgroup with no documented MI also derived enhanced benefit from CRT-D (HR = 0.43; P = 0.003)., Conclusion: In patients with ischaemic cardiomyopathy, the risk of HF or death and the magnitude of CRT-D benefit are directly related to elapsed time from MI.

Aims: To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT., Methods and Results: We studied 761 patients in New York Heart Association I/II, ejection fraction ≤30%, and QRS ≥130 ms [n = 434, CRT-defibrillator (CRT-D), n = 327, ICD] with echocardiographic studies available at baseline and 12 months. Dyssynchrony was determined as the standard deviation of time to peak transverse strain between 12 segments of apical four- and two-chamber views, and contractile function as global longitudinal strain (GLS) by averaging longitudinal strain over these 12 segments. We compared changes in LV dyssynchrony and contractile function between treatment groups and assessed relationships between these changes over the first year and subsequent outcomes (median post 1-year follow-up = 14.9 months). Mean changes in LV dyssynchrony and contractile function measured by GLS in the overall population were, respectively, -29 ± 83 ms and -1 ± 2.9%. However, both LV dyssynchrony (CRT-D: -47 ± 83 ms vs. ICD: -6 ± 76 ms, P < 0.001) and contractile function (CRT-D: -1.4 ± 3.1% vs. ICD: -0.4 ± 2.5%, P < 0.001) improved to a greater extent in the CRT-D group compared with the ICD-only group. A greater improvement in dyssynchrony and contractile function at 1 year was associated with lower rates of the subsequent primary outcome of death or heart failure, adjusting for baseline dyssynchrony and contractile function, treatment arm, ischaemic status, and change in LV end-systolic volume. Each 20 ms decrease in LV dyssynchrony was associated with a 7% reduction in the primary outcome (P = 0.047); each 1% improvement in GLS over the 12-month period was associated with a 24% reduction in the primary outcome (P < 0.001)., Conclusion: Cardiac resynchronization therapy resulted in a significant improvement in both LV dyssynchrony and contractile function measured by GLS compared with ICD only and these improvements were associated with better subsequent outcomes.

Aims: There are no data regarding the differential response to cardiac resynchronization therapy with defibrillator (CRT-D) by the aetiology of cardiomyopathy in mildly symptomatic patients. We evaluated the outcome of patients enrolled in MADIT-CRT by ischaemic and non-ischaemic aetiology of cardiomyopathy (ICM and non-ICM, respectively)., Methods and Results: The clinical response to CRT-D was assessed among ICM (n = 1046) and non-ICM (n = 774) patients enrolled in MADIT-CRT during an average follow-up of 2.4 years, and echocardiographic response was assessed at 1 year. Cardiac resynchronization therapy with defibrillator vs. ICD therapy was associated with respective 34% (P = 0.001) and 44% (P = 0.002) reductions in the risk of heart failure or death among ICM and non-ICM patients (P for interaction = 0.455). In the ICM group, CRT-D was associated with mean (±SD) 29 ± 14% and 18 ± 10% reductions in left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV), respectively. In the non-ICM group, CRT-D was associated with significantly greater volume reductions compared with the ICM group [37 ± 16% and 24 ± 12% reductions in LVESV and LVEDV, respectively (P < 0.001 for all)]. Risk subsets in the ICM group that showed a favourable clinical response to CRT-D included patients with QRS ≥150 ms, systolic blood pressure <115 mmHg, and left bundle branch block (LBBB), whereas in the non-ICM group females, patients with diabetes mellitus, and LBBB, displayed a favourable clinical response., Conclusion: Mildly symptomatic ICM and non-ICM patients show significant differences in the echocardiographic response to CRT-D and in the clinical benefit within risk subsets suggesting that risk assessment for CRT-D in this population should be aetiology-specific.

Background: Despite benefits of cardiac resynchronization therapy (CRT) in patients with severe but less symptomatic heart failure, approximately 30% of patients do not fully respond to treatment. We hypothesized that a combined assessment of left ventricular (LV) dyssynchrony and contractile function by strain-based imaging would identify patients who would most benefit from CRT., Methods and Results: We studied 1077 patients with New York Heart Association class I/II, LV ejection fraction ≤30% and QRS width ≥130 ms enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial with sufficient echocardiographic image quality for cardiac deformation analysis (implantable cardioverter-defibrillator [ICD], n=416; CRT, n=661). Patients were assigned to CRT plus an ICD or to ICD alone in 3:2 random assignment. We assessed the degree to which baseline echocardiographic assessments of dyssynchrony, measured as the standard deviation of time-to-peak transverse strain over 12 segments, contractile function, measured as global longitudinal strain, or both predicted the effect of treatment on the primary outcome of death or heart failure. With 213 primary events occurring over a mean of 2.4 years, the benefit of CRT plus an ICD relative to ICD alone was greatest in patients with mild to moderate dyssynchrony (time-to-peak transverse strain standard deviation, 142 to 230 ms) and greater baseline contractile function (global longitudinal strain ≤-8.7%). Overall, those patients with mild to moderate dyssynchrony and those with best contractile function at baseline demonstrated the greatest benefit from CRT (adjusted hazards ratio, 0.20; 95% confidence interval, 0.09 to 0.44). Dyssynchrony and global longitudinal strain predicted response to CRT independent of each other, QRS width, LV ejection fraction, and presence versus absence of left bundle-branch block, although the observed benefit remained greatest in patients with left bundle-branch block., Conclusions: Both mechanical dyssynchrony and contractile function are important independent correlates of benefit from CRT., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Background: This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial., Methods and Results: Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P < 0.001) lower in LBBB patients (0.47; P < 0.001) than in non-LBBB patients (1.24; P = 0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P < 0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients., Conclusions: Heart failure patients with New York Heart Association class I or II and ejection fraction ≤ 30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances)., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Objectives: The purpose of this study was to investigate the factors related to sex-specific outcomes for death and heart failure events in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial., Background: In the MADIT-CRT trial, women seemed to achieve a better result from resynchronization therapy than men., Methods: All 1,820 patients (453 female and 1,367 male) enrolled in the MADIT-CRT trial were included in this sex-specific outcome analysis that compared the effect of cardiac resynchronization therapy with defibrillator (CRT-D) relative to implanted cardioverter-defibrillator (ICD) on death or heart failure (whichever came first), heart failure only, and death at any time., Results: Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block and less likely to have renal dysfunction than male patients. Overall, female patients had a better result from CRT-D therapy than male patients, with a significant 69% reduction in death or heart failure (hazard ratio: 0.31, p < 0.001) and 70% reduction in heart failure alone (hazard ratio: 0.30, p < 0.001). Women had a significant 72% reduction in all-cause mortality in the total population (hazard ratio: 0.28, p = 0.02) and significant 82% and 78% reductions in mortality in those with QRS ≥ 150 ms and with left bundle branch block conduction disturbance, respectively, with sex-by-treatment interactions for mortality reduction significant at p < 0.05 in each of these 3 patient groups. These beneficial CRT-D effects among women were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men., Conclusions: Women in the MADIT-CRT trial obtained significantly greater reductions in death or heart failure (whichever came first), heart failure alone, and all-cause mortality with CRT-D therapy than men, with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) plus implantation of an implantable cardioverter defibrillator (ICD) reduced the risk of death or heart failure event in patients with mildly symptomatic heart failure, left ventricular dysfunction, and wide QRS complex compared with an ICD only. We assessed echocardiographic changes in patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function., Methods and Results: A total of 1,820 patients were randomly assigned to CRT plus an ICD or to an ICD only in a 3:2 ratio. Echocardiographic studies were obtained at baseline and 12 months later in 1,372 patients. We compared changes in cardiac size and performance between treatment groups and assessed the relationship between these changes over the first year, as well as subsequent outcomes. Compared with the ICD-only group, the CRT-plus-ICD group had greater improvement in left ventricular end-diastolic volume index (-26.2 versus -7.4 mL/m(2)), left ventricular end-systolic volume index (-28.7 versus -9.1 mL/m(2)), left ventricular ejection fraction (11% versus 3%), left atrial volume index (-11.9 versus -4.7 mL/m(2)), and right ventricular fractional area change (8% versus 5%; P<0.001 for all). Improvement in end-diastolic volume at 1 year was predictive of subsequent death or heart failure, with adjustment for baseline covariates and treatment group; each 10% decrease in end-diastolic volume was associated with a 40% reduction in risk (P<0.001)., Conclusions: CRT resulted in significant improvement in cardiac size and performance compared with an ICD-only strategy in patients with mildly symptomatic heart failure. Improvement in these measures accounted for the outcomes benefit. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Background: This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex., Methods: During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments., Results: During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups., Conclusions: CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.), (2009 Massachusetts Medical Society)

Aims: The association of psychosocial and physical factors with health outcome in patients with congestive heart failure (CHF) has not been fully explored. The aim of this study was to assess the physical and mental health in relationship to health outcome in post-infarction patients with advanced left ventricular dysfunction., Methods and Results: A total of 1058 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) completed the Medical Outcome Trust Short Form (SF-12) at baseline. Physical component summary (PCS) and mental component summary (MCS) of SF-12 were analysed in relationship to survival, hospitalization due to CHF, and implantable cardioverter-defibrillator (ICD) therapy. Both baseline PCS and MCS were significantly associated with death (P < 0.001 and P < 0.016, respectively) and hospitalization due to CHF (P

Background: Implantable cardioverter-defibrillator (ICD) therapy may be associated with an increased risk for heart failure (HF). The present study evaluated the frequency, causes, and consequences of HF after ICD implantation., Methods and Results: We performed a retrospective analysis of the clinical factors and outcomes associated with postenrollment HF events in 1218 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II. The adjusted hazard ratios (HRs) of ICD:conventional therapy for first and recurrent HF events were 1.39 (P=0.02) and 1.58 (P<0.001), respectively. The risk was increased among patients who received single-chamber or dual-chamber ICDs. Development of HF was associated with an increased mortality risk (HR, 3.80; P<0.001). Among patients who received a single-chamber ICD, there was a similar survival benefit before and after the development of HF (HR, 0.59 and 0.61, respectively; P=0.92 for difference), whereas among patients with dual-chamber devices, there was a significant reduction in survival benefit after HF (HR, 0.26 and 0.83, respectively; P=0.01 for difference). Within the defibrillator arm of the trial, patients who received life-prolonging therapy from the ICD had an increased risk for first and recurrent HF events (HR, 1.90; P=0.01 and 1.74; P<0.001, respectively)., Conclusions: Patients with chronic ischemic heart disease who are treated with either single-chamber or dual-chamber ICDs have improved survival but an increased risk of HF. The present data suggest that ICD therapy transforms sudden death risk to a subsequent HF risk. These findings should direct more attention to the prevention of HF in patients who receive an ICD.

Background: Coronary revascularization (CR) may confer electrical stability in patients with ischemic cardiomyopathy. However, data regarding the effect of CR on the development of ventricular tachyarrhythmias in this population are limited. Objective: The purpose of this study was to evaluate the association between CR and arrhythmic risk in postmyocardial infarction (post-MI) patients with left ventricular dysfunction. Methods: The risk for life-threatening ventricular tachyarrhythmias (defined as a first appropriate defibrillator therapy for ventricular tachycardia [VT]/ventricular fibrillation [VF] or death) was compared between post-MI patients with and those without prior CR (n = 612 and 147, respectively) enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT). Results: The 3-year cumulative rate of VT/VF or death was significantly higher among patients without prior CR (42%) than in patients who underwent prior CR (32%, P = .02). Multivariate analysis demonstrated that patients without prior CR had 48% increased risk (P = .01) for VT/VF or death. Risk reduction associated with CR was related to elapsed time from CR, assessed both as a categorical variable (tertiles for time from CR: ≥7 years, hazard ratio [HR] = 1.93, P = .001; 1.5–7 years, HR = 1.70, P = .01 vs <1.5 years) and as a continuous measure (4%, P = .002, increased risk for VT/VF or death per 1-year increment of elapsed time from CR). The effect of CR on arrhythmic risk was similar in patients treated with a defibrillator alone or when combined with cardiac resynchronization therapy. Conclusion: Post-MI patients with left ventricular dysfunction who undergo CR experience a time-dependent reduction in the risk for subsequent life-threatening ventricular tachyarrhythmias. [ABSTRACT FROM AUTHOR]

The planned MADIT-CRT trial is designed to determine if CRT-D will reduce the risk of mortality and HF events by approximately 25% in subjects with ischemic (NYHA class I-II) and non-ischemic (NYHA class II) cardiomyopathy, left ventricular dysfunction (EF ≤ 0.30), and prolonged intraventricular conduction (QRS duration ≥ 130 ms). [ABSTRACT FROM AUTHOR]

Objectives: We sought to evaluate the influence of single- versus dual-chamber implantable cardioverter defibrillators (ICDs) on the occurrence of heart failure and mortality as well as appropriate and inappropriate ICD therapy in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). Background: In MADIT-II, ICD therapy in patients with a prior myocardial infarction and ejection fraction ≤0.30 was associated with a 31% reduction in risk of mortality when compared to conventionally treated patients. An unexpected finding was an increased occurrence of hospitalization for heart failure in the ICD group. Methods: Data from 717 patients randomized to ICD therapy with single- or dual-chamber pacing devices in MADIT-II were retrospectively analyzed. Endpoints selected for analysis included death from any cause, new or worsening heart failure requiring hospitalization, death or heart failure, appropriate therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), and inappropriate ICD therapy for atrial fibrillation or supraventricular tachycardia. Results: A total of 404 single-chamber ICDs (S-ICDs) and 313 dual-chamber ICDs (D-ICDs) were implanted. Patients receiving D-ICDs were at a higher risk at baseline than those receiving S-ICDs, with older age, higher NYHA class, more frequent prior CABG, wider QRS complex, more LBBB, higher BUN level, a history of more atrial arrhythmias requiring treatment, and a longer time interval from their index myocardial infarction to enrollment. While there was a trend toward an increase in adverse outcomes in the D-ICD group, no statistically significant differences in heart failure or mortality were observed between S-ICD versus D-ICD groups. Conclusions: Patients with D-ICDs had a nonsignificant trend toward higher mortality and heart failure rates than patients with S-ICDs. [ABSTRACT FROM AUTHOR]

Right Ventricular Pacing in the MADIT II Trial. Introduction:This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome.Methods and Results:Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0–50% and 51–100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age≥65 years, advanced NYHA heart failure class, LVEF<0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio= 1.93; P= 0.002) and VT/VF requiring ICD therapy (HR= 1.50; P= 0.02).Conclusions:Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.(J Cardiovasc Electrophysiol, Vol. 16, pp. 359-365, April 2005) [ABSTRACT FROM AUTHOR]

FELDMAN, A. M., et al.: Use of a Wearable Defibrillator in Terminating Tachyarrhythmias in Patients at High Risk for Sudden Death: Results of WEARIT/BIROAD. The automatic ICD improves survival in patients with a history of sudden cardiac arrest. However, some patients do not meet the guidelines for ICD implantation or are unable to receive an implantable device. This study tested the hypothesis that these patients could benefit from a wearable cardioverter defibrillator. Patients with symptomatic heart failure and an ejection fraction of <0.30 (WEARIT Study) or patients having complications associated with high risk for sudden death after a myocardial infarction or bypass surgery not receiving an ICD for up to 4 months (BIROAD Study) were enrolled into two studies. After a total of 289 patients had been enrolled in the trial (177 in WEARIT and 112 in BIROAD), prespecified safety and effectiveness guidelines had been met. Six (75%) of eight defibrillation attempts were successful. Six inappropriate shock episodes occurred during 901 months of patient use (0.67% unnecessary shocks per month of use). Twelve deaths occurred during the study 6 sudden deaths: 5 not wearing and 1 incorrectly wearing the device). Most patients tolerated the device although 68 patients quit due to comfort issues or adverse reactions. The results of the present study suggest that a wearable defibrillator is beneficial in detecting and effectively treating ventricular tachyarrhythmias in patients at high risk for sudden death who are not clear candidates for an ICD and may be useful as a bridge to transplantation or ICD in some patients. (PACE 2004; 27:4–9) [ABSTRACT FROM AUTHOR]

A response by Arthur J. Moss and W. Jackson Hall to a letter to the editor about their article "Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events" in the October 1, 2009 issue is presented.

Objectives: This study aimed to evaluate the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risks of first and recurrent ventricular tachyarrhythmic events (VTEs) in the MADIT-CRT. Background: Reverse remodeling associated with CRT-D therapy was suggested to reduce arrhythmic risk. However, the effect of the device on the risk of recurrent VTEs among patients who experience a first arrhythmic event has not been investigated. Methods: The CRT-D versus defibrillator-only risks for first and subsequent fast VTEs (>180 beats/min) were assessed by Cox proportional hazards and Andersen-Gill proportional intensity regression modeling, respectively, in efficacy analyses recognizing active device-type during follow-up. Results: Multivariate analysis showed that CRT-D was associated with a significant 29% (p = 0.003) reduction in the risk of a first VTE, with a pronounced effect among patients with left bundle branch block (LBBB) (hazard ratio [HR]: 0.58; p < 0.001) and no significant effect among non-LBBB patients (HR: 1.05; p = 0.82, p for the difference = 0.02). Patients with LBBB who experienced a first VTE had no change in the risk of subsequent VTEs with CRT-D (HR: 0.98; p = 0.85). In contrast, the risk of recurrent VTEs with CRT-D was significantly increased among non-LBBB patients (HR: 3.62; p = 0.002, p for the difference = 0.009). Recurrent VTEs increased the risk of subsequent heart failure or death. Conclusions: In MADIT-CRT, active treatment with CRT-D was associated with a significant reduction in the risk of life-threatening VTEs. However, our findings suggest that CRT-D does not reduce the risk of subsequent VTEs in patients who experience a first arrhythmic event and may increase subsequent arrhythmic risk in non-LBBB patients. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271) [ABSTRACT FROM AUTHOR]

Objectives: This study hypothesized that time-dependent statin therapy will reduce the risk of life-threatening ventricular tachyarrhythmias among patients with nonischemic cardiomyopathy (NICM) enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). Background: Prior studies suggested that statin therapy exerts antiarrhythmic properties among patients with coronary artery disease. However, data regarding the effect of statins on arrhythmic risk among patients with NICM are limited. Methods: Multivariate Cox proportional hazards regression modeling was used to assess the effect of statin therapy, evaluated as a time-dependent covariate, on the risk of appropriate defibrillator therapy for fast ventricular tachycardia (VT) (defined as a rate faster than 180 beats/min)/ventricular fibrillation (VF) or death (primary endpoint) and appropriate defibrillator shocks (secondary endpoint) among 821 patients with NICM enrolled in the MADIT-CRT trial. Results: Statin users (n = 499) were older and had a higher prevalence of diabetes and hypertension yet were less frequently smokers. Multivariate analysis showed that time-dependent statin therapy was independently associated with a significant 77% reduction in the risk of fast VT/VF or death (p < 0.001) and with a significant 46% reduction in the risk of appropriate implantable cardioverter defibrillator shocks (p = 0.01). Consistent with these findings, the cumulative probability of fast VT/VF or death at 4 years of follow-up was significantly lower among patients who were treated with statins (11%) as compared with study patients who were not treated with statins (19%; p = 0.006 for the overall difference during follow-up). Conclusions: Statin use was associated with a significant reduction in the risk of life-threatening ventricular tachyarrhythmias among patients with NICM. [ABSTRACT FROM AUTHOR]

Background-Women with congenital long-QT syndrome experience an increased risk for cardiac events after the onset of adolescence that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population. Methods and Results-We used a repeated-events analysis to evaluate the risk for recurrent syncope during the menopause transition and postmenopausal periods (5 years before and after the age at onset of menopause, respectively) among 282 LQT1 (n = 151) and LQT2 (n= 131) women enrolled in the Long-QT Syndrome Registry. Multivariate analysis showed that the risk for recurrent syncope (n =150) among LQT2 women was significantly increased during both menopause transition (hazard ratio, 3.38; P= 0.005) and the postmenopausal period (hazard ratio, 8.10; P<0.001) compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction). Only 22 women (8%) experienced aborted cardiac arrest or sudden cardiac death during follow-up. The frequency of aborted cardiac arrest sudden cardiac death showed a similar genotype-specific association with the onset of menopause. Conclusions-The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population. [ABSTRACT FROM AUTHOR]

Location (anterior) and type (Q wave) of myocardial infarction (MI) might be considered of prognostic significance when predicting mortality. However, there are limited data regarding the prognostic significance of type and location of MI in patients with severely depressed left ventricular function. In 1,221 patients in the MADIT II, Q-wave MI was observed in 763 patients (62%), 115 (10%) had non–Q-wave MI, and 343 (28%) had conduction abnormalities. In patients with Q-wave MI, anterior MI was present in 430 (57%), inferior in 155 (20%), and combined in 178 (23%) patients. Study end points included all-cause mortality, hospitalization or death due to worsening congestive heart failure, and episodes of ventricular tachycardia or ventricular fibrillation requiring implantable cardioverter-defibrillator therapy. In a multivariate Cox proportional hazard model predicting mortality, the following clinical variables entered the predictive model at a p value <0.10: treatment (implantable cardioverter-defibrillator vs conventional therapy), age dichotomized at 65 years, angina pectoris, ejection fraction dichotomized at 25%, serum urea nitrogen dichotomized at 25 mg/dl, and β-blocker use. After adjustment for these covariates, risk of mortality was not significantly different in non–Q-wave MI versus Q-wave MI. However, when analyzing location of MI, inferior wall MI was associated with a significantly (hazard ratio 1.58, p = 0.048) higher risk of mortality than anterior wall MI. In addition, patients with conduction abnormalities had a higher risk of mortality (hazard ratio 1.36, p = 0.088) than patients with anterior wall MI. In conclusion, in the setting of severely depressed ejection fraction (≤30%), inferior wall MI was associated with a significantly higher risk of mortality than anterior wall MI. [Copyright &y& Elsevier]