Gender Differences in Mechanical Circulatory Support, Heart Transplantation, and Survival Among Patients with Advanced Heart Failure

Objective: Despite growing awareness of sex-based disparities in heart failure (HF), their impact on clinical outcomes in advanced stages remains poorly understood, largely due to confounding in observational data. This study aimed to assess the independent effect of biological sex on clinical outcomes in advanced HF.

Method: In this retrospective cohort study, 522 patients with advanced HF (85.2% male) evaluated between 2021 and 2024 underwent comprehensive assessments, including echocardiography, cardiopulmonary exercise testing, and cardiac catheterization. Covariate balance was achieved using inverse probability weighting (IPW) based on propensity scores. Primary outcomes included left ventricular assist device (LVAD) implantation, heart transplantation, all-cause mortality, and a composite of these events. Cox proportional hazards models were applied, with a median follow-up of 864 days.

Results: At baseline, male patients were older (54.0 vs. 49.5 years; P = 0.025), had higher rates of ischemic etiology (49.9% vs. 22.7%; P < 0.001), larger cardiac dimensions, and superior exercise capacity. Following IPW adjustment, female sex was associated with a significantly lower risk of LVAD implantation (hazard ratio [HR]: 0.13; 95% confidence interval [CI]: 0.04–0.40; P < 0.001). In contrast, no significant sex-related difference was found in all-cause mortality (HR: 0.75; 95% CI: 0.36–1.58; P = 0.43). The composite outcome showed a non-significant trend toward better outcomes in women (HR: 0.53; 95% CI: 0.26–1.06; P = 0.076). These findings should be interpreted in the context of the relatively small female cohort (14.8%).

Conclusion: In patients with advanced HF, female sex was associated with a lower likelihood of LVAD implantation without an effect on overall mortality. These findings suggest that advanced HF may follow distinct pathophysiological trajectories in women and men, underscoring the importance of sex-informed clinical decision-making frameworks to optimize management and outcomes.

Keywords: Advanced heart failure, sex differences, left ventricular assist device, mechanical circulatory support, inverse probability weighting, propensity score