Cardiac Resynchronization in Women: A Substudy of the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial

Objectives: This study sought to evaluate the effect of cardiac resynchronization therapy with defibrillator (CRT-D) as compared with implantable cardioverter-defibrillator (ICD) on mortality, heart failure (HF) hospitalization, and ventricular arrhythmia in women versus men. Background: CRT-D has demonstrated reduced mortality and HF hospitalizations with greater benefit observed in women compared with men. However, whether CRT-D prevented ventricular arrhythmias in women compared with men was unclear. Methods: The RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study randomized 1,798 patients to an ICD or CRT-D. In this post hoc analysis, women and men were compared by randomized group. By using a multivariable model, the outcomes of death and HF hospitalization and incidence of ventricular arrhythmia were compared between men and women. Results: There were 1,490 (83%) men (732, ICD; 758, CRT-D) and 308 (17%) women (172, ICD; 136, CRT-D) included in the analysis. Women with CRT-D had a significantly reduced incidence of death and HF hospitalization compared with men with CRT-D (hazard ratio: 0.52; 95% confidence interval: 0.33 to 0.81; p < 0.001) on multivariable analysis. Women with a primary prevention indication and CRT-D had the lowest rate of ventricular arrhythmia compared with men (hazard ratio: 0.59; 95% confidence interval: 0.39 to 0.91; p = 0.016). Conclusions: Women have improved rates of death and HF hospitalization with CRT-D and were less likely to experience ventricular arrhythmia when compared with men, after adjusting for differences in baseline characteristics over a prolonged follow-up. Whether these improved outcomes reflect inherent sex differences in the underlying myocardial substrate resulting in an enhanced response to CRT-D requires further research.