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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.

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., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) showed a significant 31 reduction in the risk of death with primary implantable cardioverter-defibrillator (ICD) therapy during a median follow-up of 1.5 years. However, currently there are no data on the long-term efficacy of primary defibrillator therapy., Methods and Results: MADIT-II enrolled 1232 patients with ischemic left ventricular dysfunction who were randomized to ICD and non-ICD medical therapy and were followed up through November 2001. For the present long-term study, we acquired posttrial mortality data through March 2009 for all study participants (median follow-up, 7.6 years). Multivariate Cox proportional hazards regression modeling was performed to calculate the hazard ratio for ICD versus non-ICD therapy during long-term follow-up. At 8 years of follow-up, the cumulative probability of all-cause mortality was 49 among patients treated with an ICD compared with 62 among non-ICD patients (P<0.001). Multivariate analysis demonstrated that ICD therapy was associated with a significant long-term survival benefit (hazard ratio for 0- through 8-year mortality=0.66 [95 confidence interval, 0.56 to 0.78]; P<0.001). Treatment with an ICD was shown to be associated with a significant reduction in the risk of death during the early phase of the extended follow-up period (0 through 4 years: hazard ratio=0.61 [95 confidence interval, 0.50 to 0.76]; P<0.001) and with continued life-saving benefit during the late phase of follow-up (5 through 8 years: hazard ratio=0.74 [95 confidence interval, 0.57 to 0.96]; P=0.02)., Conclusions: Our findings demonstrate a sustained 8-year survival benefit with primary ICD therapy in the MADIT-II population.

Background: Data on long-term follow-up and factors influencing mortality in implantable cardioverter-defibrillator (ICD) recipients are limited., Objective: The aim of this study was to evaluate mortality during long-term follow-up and the predictive value of several risk markers in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implanted cardioverter-defibrillators (ICDs)., Methods: The study involved U.S. patients from the MADIT II trial randomized to and receiving ICD treatment. Data regarding long-term mortality were retrieved from the National Death Registry. Several clinical, biochemical, and electrocardiogram variables were tested in a multivariate Cox model for predicting long-term mortality, and a score identifying high-, medium-, and lower risk patients was developed., Results: The study population consisted of 655 patients, mean age 64 +/- 10 years. During a follow-up of up to 9 years, averaging 63 months, 294 deaths occurred. The 6-year cumulative probability of death was 40%, with evidence of a constant risk of about 8.5% per year among survivors. Median survival was estimated at 8 years. Multivariate analysis identified age >65 years, New York Heart Association class 3-4, diabetes, non-sinus rhythm, and increased levels of blood urea nitrogen as independent risk predictors of mortality. Patients with three or more of these risk factors were characterized by a 6-year mortality rate of 68%, compared with 43% in those with one to two risk factors and 19% in patients with no risk factors., Conclusion: A combination of a few readily available clinical variables indicating advanced disease and comorbid conditions identifies ICD patients at high risk of mortality during long-term follow-up.

Objectives: The study was designed to develop a simple risk stratification score for primary therapy with an implantable cardioverter-defibrillator (ICD)., Background: Current guidelines recommend primary ICD therapy in patients with a low ejection fraction (EF). However, the benefit of the ICD in the low EF population may not be uniform., Methods: Best-subset proportional-hazards regression analysis was used to develop a simple clinical risk score for the end point of all-cause mortality in patients allocated to the conventional therapy arm of MADIT (Multicenter Automatic Defibrillator Implantation Trial)-II after excluding a pre-specified subgroup of very high-risk (VHR) patients (defined by blood urea nitrogen [BUN] >or=50 mg/dl and/or serum creatinine >or=2.5 mg/dl). The benefit of the ICD was then assessed within risk score categories and separately in VHR patients., Results: The selected risk score model comprised 5 clinical factors (New York Heart Association functional class >II, age >70 years, BUN >26 mg/dl, QRS duration >0.12 s, and atrial fibrillation). Crude mortality rates in the conventional group were 8% and 28% in patients with 0 and >or=1 risk factors, respectively, and 43% in VHR patients. Defibrillator therapy was associated with a 49% reduction in the risk of death (p < 0.001) among patients with >or=1 risk factors (n = 786), whereas no ICD benefit was identified in patients with 0 risk factors (n = 345; hazard ratio 0.96; p = 0.91) and in VHR patients (n = 60; hazard ratio 1.00; p > 0.99)., Conclusions: Our data suggest a U-shaped pattern for ICD efficacy in the low-EF population, with pronounced benefit in intermediate-risk patients and attenuated efficacy in lower- and higher-risk subsets.

Background: Much of prognostic implications of ventricular arrhythmia storms remain unclear., Objective: We evaluated the risk associated with electrical storm in patients with defibrillators in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) study., Methods: Electrical storm was defined as > or =3 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) in 24 hours., Results: Of the 719 patients who received internal cardiac defibrillator (ICD) implants and had follow-up in the MADIT-II, 27 patients (4%) had electrical storm, 142 (20%) had isolated episodes of VT/VF, and the remaining 550 patients had no ICD-recorded VT events. Baseline clinical characteristics among the groups were similar. Patients who experienced electrical storm had a significantly higher risk of death. After adjustments for relevant clinical covariates, the hazard ratio (HR) for death in the first 3 months after the storm event was 17.8 (95% confidence interval [CI] 8.0 to 39.5, P <.01) in comparison with those with no VT/VF. This risk continued even after 3 months for those with electrical storm (HR of 3.5, 95% CI 1.2 to 9.8, P = .02). Study patients with isolated VT/VF episodes also were at an increased risk of dying (HR = 2.5, 95% CI 1.5 to 4.0, P <.01) when compared with patients without VT/VF episodes. Statistically significant predictors of electrical storm were interim postenrollment coronary events (myocardial infarction or angina) HR 3.1 (95% CI 1.2 to 8.1, P = .02) and isolated VT or VF HR 9.2 (95% CI 4.0 to 20.9, P <.01)., Conclusion: Postinfarction patients with severe left ventricular dysfunction in whom electrical storm developed have significantly higher mortality than patients with only isolated VT/VF as well as those without any episodes of VT/VF. Patients who experienced postenrollment ventricular arrhythmias and/or interim coronary events during follow-up were at higher risk for VT/VF storms.

Introduction: We aim to evaluate the mortality benefit from defibrillator therapy in eligible elderly patients. Effective primary prevention of sudden cardiac death with implantable cardioverter defibrillators is well demonstrated in patients with coronary disease and depressed ventricular function., Methods and Results: Among 1,232 patients enrolled with prior infarct and left ventricular ejection fraction < or = 0.30, 204 were > or = 75 years old. Of these 204 patients, 121 underwent defibrillator implant. Relative to the younger patients, those > or = 75 years had a higher incidence of atrial fibrillation, elevated blood urea nitrogen (BUN), widened QRS, and lower use of beta-blockers and HMG-CoA reductase inhibitors. Relevant clinical covariates were similar in elderly patients randomized to conventional and defibrillator therapy. The hazard ratio for the mortality risk in patients > or = 75 years assigned to defibrillator implant compared with those in conventional therapy was 0.56 (95 confidence interval 0.29-1.08; P = 0.08) after a mean follow-up of 17.2 months. Comparatively, the hazard ratio in patients < 75 years assigned to defibrillator implant was 0.63 (0.45-0.88; P = 0.01) after 20.8 months. Elderly patients had similar reductions in quality of life (QoL) regardless of treatment randomization. Scores through Health Utilities Index Mark III (HUI) Questionnaire changes from baseline to 1 year were -0.22 for patients with conventional therapy versus -0.20 for patients with ICD, and -0.36 versus -0.27 at 2 years, respectively (P = NS)., Conclusion: The implantable defibrillator is associated with an equivalent reduction of mortality in elderly and younger patients, with no compromise in the QoL in the older age subjects.

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 beta-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 (< or =30%), inferior wall MI was associated with a significantly higher risk of mortality than anterior wall MI.

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 < or =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.

In the second Multicenter Automatic Defibrillator Implantation Trial, patients with a previous myocardial infarction and left ventricular ejection fraction < or =0.30 benefited significantly from prophylactic implantable cardioverter-defibrillator (ICD) placement. Diabetic patients who had a myocardial infarction had a worse prognosis compared with nondiabetics. The present study used data from the second Multicenter Automatic Defibrillator Implantation Trial to assess the efficacy of ICD placement on survival in diabetic patients. Of the 1,232 patients in the second Multicenter Automatic Defibrillator Implantation Trial, 489 were characterized as diabetic. They were more likely to be New York Heart Association class II to IV, be hypertensive, have renal dysfunction, have an increased body mass index, and to take diuretic drugs. Diabetic patients had a 24% greater adjusted risk of death than nondiabetic patients. The hazard ratio (HR) for the risk of death in patients treated with the ICD compared with conventional therapy was similar in diabetics (HR 0.61; 95% confidence interval [CI] 0.38 to 0.98) and nondiabetics (HR 0.71; 95% CI 0.49 to 1.05), with no evidence of interaction. Thus, diabetic patients derive a similar benefit from ICD therapy despite being sicker and having a higher mortality rate overall.

Background: Prophylactic implantable defibrillators (ICDs) improve survival in patients with impaired ventricular function after myocardial infarction (MI), but it is uncertain whether mortality risk and survival benefit depend on the elapsed time from MI., Methods and Results: The Multicenter Automatic Defibrillator Implantation Trial II examined the impact of ICDs on survival in post-MI patients with ejection fractions < or =30%. In 1159 patients, mean time from most recent MI to enrollment was 81+/-78 months. Patients were randomized to an ICD (n=699) or conventional care (n=460) in a 3:2 ratio. Mortality rates (deaths per 100 person-years of follow-up) in both treatment groups were analyzed by time from MI divided into quartiles (<18, 18 to 59, 60 to 119, and > or =120 months). In conventional care patients, these rates increased as time from MI increased (7.8%, 8.4%, 11.6%, 14.0%; P=0.03). Mortality rates in ICD patients were consistently lower in each quartile and showed minimal increase over time (7.2%, 4.9%, 8.2%, 9.0%; P=0.19). Covariate-adjusted hazard ratios for risk of death associated with ICD therapy were 0.97 (95% CI, 0.51 to 1.81; P=0.92) for recent MI (<18 months) and 0.55 (95% CI, 0.39 to 0.78; P=0.001) for remote MI (> or =18 months)., Conclusions: Mortality risk in patients with ejection fractions < or =30% increases as a function of time from MI. The survival benefit associated with ICDs appears to be greater for remote MI and remains substantial for up to > or =15 years after MI.

Background: Patients with reduced left ventricular function after myocardial infarction are at risk for life-threatening ventricular arrhythmias. This randomized trial was designed to evaluate the effect of an implantable defibrillator on survival in such patients., Methods: Over the course of four years, we enrolled 1232 patients with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned in a 3:2 ratio to receive an implantable defibrillator (742 patients) or conventional medical therapy (490 patients). Invasive electrophysiological testing for risk stratification was not required. Death from any cause was the end point., Results: The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups. During an average follow-up of 20 months, the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group. The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 (95 percent confidence interval, 0.51 to 0.93; P=0.016). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, ejection fraction, New York Heart Association class, and the QRS interval., Conclusions: In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.