Heart size disparity drives sex-specific response to cardiac resynchronization therapy: a post-hoc analysis of the MORE-MPP CRT trial.

Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased "relative dyssynchrony" at given QRS durations (QRSd). Objective: To investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. Methods: A post-hoc analysis of the MORE-CRT MPP trial (n=3739, 28% female), with a sub-group analysis of patients with non-ischaemic cardiomyopathy (NICM) and left bundle branch block (LBBB) (n=1308, 41% female) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/LVEDV (left ventricular end-diastolic volume). Results: Females had a higher CRT response rate than males (70.1% vs. 56.8%, p<0.0001). Conclusions: In the NICM LBBB population, increased relative dyssynchrony in females, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150ms. Females may benefit from CRT at a QRSd <130ms, opening the debate on whether sex-specific QRSd cut-offs or QRS/LVEDV measurement should be incorporated into clinical guidelines.