Frailty and obesity in heart transplant recipients: impact on post-transplant mortality

Background Frailty and obesity are key determinants of post-transplant outcomes in patients with advanced heart failure, yet their combined impact on mortality remains unclear (1, 2). This study examines the relationship between frailty, obesity, and survival following heart transplantation. Methods We conducted a retrospective cohort study of 268 heart transplant recipients between 2013 to 2024 who underwent frailty assessment using Fried’s Frailty Phenotype (FFP) within 6 months prior to transplant. Frailty was defined as FFP ≥ 3 (45.9%, n = 123), and obesity was defined as BMI ≥ 30 kg/m² (19.8%, n = 53). Patients were classified into four frailty-obesity groups: non-frail non-obese (44.8%, n = 120), non-frail obese (9.3%, n = 25), frail non-obese (35.4%, n = 95), and frail-obese (10.4%, n = 28). The primary outcome was post-transplant all-cause mortality. Mortality differences were assessed using Kaplan-Meier analysis with log-rank tests. A Cox proportional hazards model was used to evaluate the combined effects of frailty and obesity on mortality. Results The cohort was predominantly male (68.3%, n = 183), with a median age of 54 years [IQR 42.00 - 62.00]. Post-transplant mortality differed across frailty-obesity groups. Non-frail non-obese patients had the lowest mortality rate (15%, 18/120), followed by frail non-obese (25.3%, 24/95), non-frail obese (28%, 7/25), and frail-obese (28.6%, 8/28) (p < 0.05). In the Cox proportional hazards model, frail-obese patients had the highest risk of mortality (HR = 2.66, 95% CI: 1.15–6.14, p < 0.05), and frail non-obese individuals also showed a significantly increased risk (HR = 1.96, 95% CI: 1.06–3.62, p < 0.05). The hazard ratio for non-frail obese patients (HR = 2.37, 95% CI: 0.99–5.70, p = 0.053) suggested increased risk. Conclusion While obesity is often considered protective against frailty, our findings indicate that frailty commonly occurs in obese individuals undergoing heart transplants. Post-transplant mortality was highest in frail-obese patients, demonstrating that the coexistence of frailty and obesity compounds mortality risk. These results highlight the importance of screening for frailty in all heart transplant candidates, regardless of BMI, to identify high-risk individuals who may benefit from targeted prehabilitation and post-transplant care.