Cardiac resynchronization therapy: better in women?

Abstract Introduction Women are underrepresented in cardiac resynchronization trials; however, they have been shown to derive a greater benefit from CRT compared to men. Aim To determine sex-specific differences in CRT in our population. Methods Single center retrospective study of patients (pts) submitted CRT implantation between 2017 and 2024. Echocardiographic CRT response was defined as a reduction in left ventricular end-systolic volume (LVESV)≥15% or an improvement in LVEF≥10%. Superresponse was defined as an increase in LVEF≥ 20% or a reduction in LVESV ≥30%. The mean follow-up time was 36,3± 23,9 months. Results We included 182 pts, 69% males, age 74 (IQR 66-79) years, median LVEF 29% (IQR 25-33). Males had higher rate of tobacco use (38% vs 7%, p<0,005), obstructive sleep apnoea (12% vs 2%, p= 0,026) and previous stroke (14% vs 0%, p= 0,003). Ischemic aetiology was significantly more common in males (40% vs. 18%, p = 0,003), who also had higher rates of obstructive coronary disease (63% vs. 34%, p = 0,005) and prior revascularization (43% vs. 20%, p = 0,003). Women were more likely to present with left bundle branch block (51% vs 78%, p 0,001). The mean QRS duration was 161 ±28 ms with no differences between sexes. Women presented with higher NHYA functional class (NHYA Class III-IV in 35% vs 53%, p= 0,029). No differences in LVEF between groups. Men had higher prevalence of valvular prostheses (14% vs 4%, p= 0,047), and more dilated ventricles (mean left ventricular end-diastolic volume: 107 ±35 ml/m2 vs 93 ±39 ml/m2, p=0,003; mean left ventricle diameter: 65±8 mm vs 61±7 mm, p=0,005). There were no significant differences in pre-CRT medication use, although men showed a trend toward higher use of sacubitril-valsartan (41.3% vs. 26.8%, p = 0,06). Women had higher CRT response rates compared to men (70% vs 89%, p = 0,01) and were more likely to achieve superresponse (55% vs 80%, p = 0,003). In multivariate analysis, after adjusting for possible confounders, female sex was an independent predictor of CRT response (HR 4,2, 95% CI: 1,4–12,4, p=0,008). Regarding clinical evolution, there were no differences in heart failure hospitalizations (log-rank p=0,92), but higher rates of cardiovascular mortality in men (12,8% vs 3,6%, log-rank p= 0,035). Conclusions In our cohort, women showed significantly higher response rates to cardiac resynchronization therapy (CRT) and better clinical outcomes. Despite having less dilated ventricles and larger QRS widths, female gender was independently associated with improved CRT response. The higher prevalence of ischemic aetiology may contribute the poorer prognosis in males. These findings highlight the importance of increasing female representation in CRT trials and further investigating sex-specific factors affecting CRT outcomes.