Potential mechanisms underlying the effect of gender on response to cardiac resynchronization therapy: insights from the SMART-AV multicenter trial.

BACKGROUND: Recent studies demonstrate that women may respond more favorably to cardiac resynchronization therapy (CRT) than do men. The mechanisms remain unclear. OBJECTIVES: To describe the effects of gender on response to CRT and to explore potential mechanisms behind these differences. METHODS: Data for 846 patients from the SMART-AV trial were used to evaluate the mechanisms behind the effects of gender on CRT response. Atrioventricular optimization (AVO) was performed via SmartDelay or echocardiography. Baseline and 6-month left ventricular end systolic volume index (LVESVi) were fitted to a linear regression model with gender predicting change in LVESVi and adjusted for baseline covariates significantly differing by gender. The interaction variable for AVO and gender was also assessed for its effect on change in LVESVi. RESULTS: Baseline variables, including age, body mass index, left ventricular ejection fraction, QRS width, and severity of heart failure symptoms, were comparable between men and women. Women had a higher incidence of left bundle branch block conduction and nonischemic cardiomyopathy and exhibited greater reductions in LVESVi even after adjustment for these differences (13.4 mL/m(2) vs 8.5 mL/m(2); P = .002). In addition, women had greater percentages of biventricular pacing and appeared to derive greater reductions in left ventricular volume with AVO than did men. CONCLUSIONS: Women demonstrated greater reductions in LVESVi with CRT than did men. These observations are not explained by differences in baseline characteristics. Greater degrees of biventricular pacing and enhanced response to AVO in women may partly explain the reason for the gender effect on CRT response.