Sex differences in response to cardiac resynchronization therapy: the role of relative dyssynchrony - Does size matter in sex?
L Van Pelt, J Erzeel, P Martens, C Ghossein-DohaAbstract
Background and Purpose
Women appear to have a better response to cardiac resynchronization therapy (CRT) compared to men at a shorter QRS duration, but the underlying mechanisms remain unclear. This study aimed to explore factors contributing to the improved response to CRT in women, focusing on the role of relative dyssynchrony and sex.
Methods
We analysed a cohort of heart failure patients undergoing CRT, with a focus on sex differences in treatment outcomes. Echocardiographic and MRI parameters, including left ventricular (LV) ejection fraction (LVEF), LV end-systolic volume (LVESV), and relative dyssynchrony indices (calculated from QRS duration relative to LV end-diastolic volume [QRSd/LVEDV]), were assessed. Longer QRS duration for a given LV-size (LVEDV) represents more relative dyssynchrony. Univariate and multivariate regression analyses were conducted to identify predictors of LVEF and LVESV changes, with particular attention to sex-specific differences. Predictors included age, comorbidities (such as anaemia, chronic kidney disease, atrial fibrillation, hypertension, and diabetes), and treatment regimens.
Results
Our results show that women have a significantly better response to CRT compared to men. Specifically, 89.5% of women experienced an absolute increase in LVEF of greater than 5%, compared to 72.5% of men (p<0.001). Furthermore, 74.3% of women had an improvement of more than 10%, compared to 54.2% of men (p=0.001). Univariate and multivariate analyses showed that the ratio of QRS duration to left ventricular end-diastolic volume (QRSd/LVEDV) was more strongly associated with LVEF improvement in women than in men (interaction term p<0.001). Furthermore, factors such as age, the presence of scar tissue, and non-ischemic cardiomyopathy were significant predictors of response. However, sex differences in response to CRT (>5% LVEF improvement) remained significant (p=0.003) even after adjusting for these variables. For a >10% improvement in LVEF, sex differences were no longer significant after adjustment. However, relative dyssynchrony remained a significant predictor (p=0.034), indicating that size may contribute to a greater response to CRT.
Conclusions
Women appear to respond more favorably to CRT, with a stronger association between relative dyssynchrony and LVEF improvement. This suggests that sex-specific differences in cardiac remodeling contribute to the observed disparity in treatment response, with relative dyssynchrony serving as a critical predictor of success. At a given QRS duration, a higher QRSd/LVEDV ratio indicates that prolonged QRS duration is primarily linked to dyssynchrony (the substrate for CRT), rather than to ventricular size (which does not support CRT). These findings highlight the potential for personalized CRT strategies, optimizing outcomes for both men and women.Spline: QRSd/LVEDV - LVEF changeFor image description, please refer to the figure legend and surrounding text.Multivariate backward Wald regressionFor image description, please refer to the figure legend and surrounding text.