Sex-specific response to cardiac resynchronization therapy: the BIO|WOMEN trial

Background: Variable evidence exists about the efficacy of Cardiac resynchronization therapy (CRT) in women vs. men with reduced left ventricular ejection fraction (LVEF) and wide QRS complex. Current guidelines, hindered by underrepresentation of women in clinical trials, lack definitive recommendations. The present study was designed to achieve an equal distribution of women and men to prospectively evaluate sex-specific response to CRT. Methods: The primary endpoint was the absolute increase in core-lab-assessed LVEF 12 months after de novo implantation of a CRT device. Estimation was adjusted by several baseline confounders to correct sex-specific effect of CRT. Secondary endpoints were further echocardiographic changes including responder rate (LVEF increase ≥5 %); change in NYHA class, 6-min walk distance, quality of life, a clinical composite score (CCS) and the composite of death or HF hospitalization. Results: We enrolled 230 women and 244 men at 25 sites in eight countries. A larger improvement in LVEF (+14.7 % vs. +11.5 %, p ≤ 0.01) in women remained after adjustment for baseline variables (absolute increase attributed to female sex +2.53 %, P = 0.023). Furthermore, a better improvement was observed in reverse remodeling, responder rate (∆LVEF ≥5 %: 83.3 % vs. 70.6 %; p = 0.003), quality of life and HF symptoms in women compared to men. The CCS and the composite of death or HF hospitalization were better in women than in men after CRT. Conclusions: The effect of CRT remained superior in women regarding echocardiographic outcomes even after adjusting for baseline variables. Our results confirm the importance of recognizing sex-specific differences when screening patients for CRT.