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Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs).Objectives: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD.Methods: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy.Results: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life.Conclusions: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253). [ABSTRACT FROM AUTHOR]

Background A high percentage of biventricular pacing is required for optimal outcome in patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established. Objectives This study sought to determine if increased ectopic beats reduce the chance of high biventricular pacing percentage and are associated with subsequent adverse outcomes. Methods From the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 801 patients with an implanted CRT-defibrillator device with data available on biventricular pacing percentage and pre-implantation 24-h Holter recordings were included. Using logistic regression, we estimated the influence of ectopic beats on the percentage of biventricular pacing. Reverse remodeling was measured as reductions in atrial and left ventricular end-systolic volumes (LVESV) at 1 year. Cox models were used to assess the influence of ectopic beats on the outcomes of heart failure (HF) or death, ventricular tachyarrhythmias (VTAs), and death. Results In the pre-implantation Holter recording, ectopic beats accounted for a mean 3.2 ± 5.5% of all beats. The probability of subsequent low biventricular pacing percentage (<97%) was increased 3-fold (odds ratio: 3.37; 95% confidence interval: 1.74 to 6.50; p < 0.001) in patients with 0.1% to 1.5% ectopic beats and 13-fold (odds ratio: 13.42; 95% confidence interval: 7.02 to 25.66; p < 0.001) in patients with >1.5% ectopic beats compared with those with <0.1% ectopic beats. Patients with ≥0.1% ectopic beats had significantly less reverse remodeling (percent reduction in LVESV 31 ± 15%) than patients with <0.1% ectopic beats (percent reduction in LVESV 39 ± 14%; p < 0.001). The risk of HF/death and VTA was increased significantly in those with 0.1% to 1.5% ectopic beats (hazard ratio: 3.13 and 1.84, respectively) and for >1.5% ectopic beats (hazard ratio: 2.38 and 2.74, respectively). Conclusions Relatively low frequencies of ectopic beats (≥0.1%) dramatically increase the probability of low biventricular pacing (<97%), with reduced CRT efficacy by less reverse remodeling and higher risk of HF/death and VTA. This supports pre-implantation Holter monitoring of patients selected for CRT for optimal outcome. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271 ) [ABSTRACT FROM AUTHOR]