Abstract Background Women have been previously shown to be at a lower risk of ventricular tachyarrhythmia (VT) events in ICD trials, however, more contemporary data on the risk of VT/VF and death by sex in patients with prior VT/VF are lacking. Objective We aimed to assess sex-differences in ICD-treated VT/VF events and all-cause mortality in patients in the Ranolazine in High-Risk ICD Patients (RAID) trial. Patients were either implanted for secondary prevention or primary prevention ICD indications but experienced VT/VF before enrolment. Methods The RAID trial enrolled high-risk ICD patients with ischemic or non-ischemic cardiomyopathy, randomized to ranolazine or placebo. This analysis focused on patients with prior VT/VF. Sex-differences in VT/VF requiring ATP or shock were evaluated using Kaplan-Meier analysis, Fine and Grey, and Cox models in an intention to treat analysis. All VT/VF episodes were centrally adjudicated. Results There were 124 women (17%) out of 714 subjects analysed. Women were younger (60 vs. 65 years, p<0.001), more often non-ischemic (70% vs. 37%, p<0.001), less often had hypertension (69% vs. 78%, p=0.045) and diabetes (19% vs. 34%, p=0.002). Compared to men, women were at a significantly lower risk of VT/VF/Death (HR=0.67, [95% CI, 0.46-0.96], p=0.029), lower risk of VT/VF (HR=0.68, [95% CI, 0.46-1.00], p=0.049), lower risk of VT/VF treated with ATP (HR=0.59, [95% CI, 0.38-0.92], p=0.019), and lower risk of VT/VF treated with ICD shock (HR=0.54, [95% CI, 0.31-0.96], p=0.035). The risk of recurrent VT/VF was also significantly lower in woman (HR=0.35 [95% CI, 0.26-0.48], p<0.001). Hazard ratio for death was similar to the other endpoints, (HR=0.61, [95% CI 0.30-1.22] p=0.162) but did not reach statistical significance, most probably related to low statistical power due the relatively small number of death events among women. The effect of ranolazine on endpoints did not differ by sex. Conclusions Women with a history of prior VT/VF and managed with an ICD/CRT-D experienced a lower risk recurrent VT/VF requiring device therapy as compared with men. The risk of mortality showed a similar trend although did not reach significance.
The implantable cardioverter–defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects.
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.
Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs).This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD.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.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.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).
The implantable cardioverter defibrillator (ICD) is highly effective in reducing mortality due to cardiac arrhythmias in high‐risk cardiac patients. However, inappropriate therapies caused predominantly by supraventricular tachyarrhythmias (SVTs) remain a significant side effect of ICD therapy despite medical treatment, affecting 8–40% of patients. The MADIT‐RIT is a global, prospective, randomized, nonblinded, three‐arm, multicenter clinical investigation to be performed in the Unites States, Europe, Canada, Israel and Japan, and will utilize approximately 90 centers with plan to enroll 1500 patients programmed to three treatment arms. The objective of the MADIT‐RIT trial is to determine if dual‐chamber ICD or CRT‐D devices with high rate cutoff (MADIT‐RIT‐Arm B) and/or long delay in combination with detection enhancements (MADIT‐RIT‐Arm C) are associated with fewer patients experiencing inappropriate therapies than standard programming (MADIT‐RIT‐Arm A) during postimplant follow‐up of patients with indication for primary prevention device therapy. This paper describes design and analytic plan for the MADIT‐RIT trial.
There is no clear consensus regarding the optimal risk stratification of high-degree atrioventricular block (HDAVB) after transcatheter aortic valve replacement (TAVR).
Introduction: There are limited data on the risk of inappropriate and appropriate ICD therapy and on the efficacy of different ICD programing strategies as a function of race. Methods: In MADIT-RIT, we evaluated the risk of inappropriate and appropriate ICD therapy by self identified race, and assessed the efficacy of improved ICD programming with either a high rate cut-off VT zone ≥ 200 bpm (Arm B), or long 60 sec delay in the VT zone 170-190 bpm (Arm C), as compared to conventional ICD programming with 2.5 sec delay beginning at 170 bpm (Arm A) among black and white patients. Results: MADIT-RIT enrolled 272 (20%) black and 1119 (80%) white patients. Black patients were younger, more often females, they more often had non-ischemic etiology of cardiomyopathy, a narrower QRS and they were less often implanted with CRT-D. The risk of inappropriate ICD therapy was similar among black and white patients (HR 1.25, 95% CI 0.82-1.93, P=0.30) after adjustment for relevant covariates. High rate cut-off or delayed VT therapy was associated with significant reductions in inappropriate ICD therapy among white patients (Arm B vs. Arm A, HR 0.15, P<0 .0001, Arm C vs. Arm A, HR 0.19, P 0.10). However, delayed VT therapy (Arm C) when compared to Arm A, was associated with greater reduction in appropriate ICD therapy in black patients (HR 0.08, P<0.0001), as compared to white patients (HR 0.27, P<0.0001, P interaction=0.07). There were no appropriate ICD therapies in the 170-200 bpm range in Arm C with delayed VT therapy programming in black patients, and a further reduction in appropriate ICD therapy ≥ 200 bpm (Arm C vs. Arm A, HR=0.16, p<0.001). Conclusion: In MADIT-RIT, there were similar reductions in inappropriate ICD therapy among black and white patients with improved ICD programming. However, black patients derived more benefit from delayed VT zone programming with greater reduction in appropriate ICD therapy compared to whites, due to a higher rate of self-terminating VT events.
Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no–beta‐blocker group (hazard ratio,1.997; 95% CI, 1.118–3.568; P <0.02), the >0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094–3.016; P <0.02), and the >25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105–2.815; P <0.02), compared with the >12.5% to 25% dose group. The mortality in the full‐dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687–2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta‐blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta‐blocker and other beta‐blocker doses. A new paradigm for post‐MI beta‐blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.
