Cardiac resynchronization therapy outcomes by sex and QRS duration: insights from AdaptResponse and a Real-world registry

Background Sex-related differences in cardiac resynchronization therapy (CRT) outcomes in heart failure (HF) patients, particularly at shorter QRS durations, remain incompletely defined. We evaluated outcomes by sex and QRS duration in AdaptResponse trial and, pooled with Medtronic product surveillance registry (PSR) data, evaluated mortality comparing CRT and no CRT.Methods and results AdaptResponse patients (symptomatic HF, LVEF≤35%, Strauss-LBBB, and normal atrioventricular conduction; 43% women) were analyzed by sex and baseline QRS (150ms cut-off), and pooled with PSR CRT and No CRT groups meeting CRT indications. Average treatment effect on treated (ATT) propensity weighting was used to standardize the PSR groups to AdaptResponse baseline characteristics. All-cause mortality was compared between the pooled CRT patients and No CRT controls with weighted Cox models. In AdaptResponse, adjusted mortality rates did not differ significantly between women and men (HR 0.91, 95% CI: 0.72-1.15; p=0.45), and no interaction was observed between sex and QRS (p=0.31). Adjusted mortality in women with QRSConclusion In this exploratory analysis, among patients with QRS 120-149ms, CRT was associated with a 49% and 50% relative mortality reduction in men and women, respectively, through five years of follow-up compared to No CRT controls. In AdaptResponse, mortality in women with these shorter QRS durations was similar to men with QRS≥150ms. These observational findings are hypothesis-generating and suggest a potential benefit of CRT in this patient population, particularly for women, but have not been confirmed in a randomized trial.