Resynchronising care: addressing sex differences in cardiac resynchronisation therapy

Despite compelling evidence for sex-based differences in cardiovascular disease, current guidelines for cardiac resynchronisation therapy (CRT) remain predominantly informed by male-centric data. Heart failure with reduced ejection fraction (HFrEF) is less prevalent in female individuals. As a result, female patients were less frequently enrolled in early landmark CRT trials (comprising only ∼20% of participants), thus limiting the statistical power needed to detect meaningful female-specific outcomes. Emerging evidence suggests that female patients derive greater benefit from CRT at shorter QRS durations (130-149 ms) compared to male patients (≥150 ms), particularly those with left bundle branch block and non-ischaemic cardiomyopathy. Structural, electrical, and device programming differences may contribute to enhanced reverse remodelling and better clinical outcomes in females. However, these findings are seldomly reflected in guideline recommendations and rarely impact clinical decision-making, leading to underuse of CRT in eligible female patients. This Viewpoint calls for the integration of sex-specific analyses in CRT research, sex-specific recommendations in guidelines, and enhanced clinician awareness of sex-based differences.