Obesity, frail obesity, and outcomes after durable left ventricular assist device implantation: a pooled analysis of the MOMENTUM 3 trials

Background and Aims Obesity in patients supported by left ventricular assist devices (LVADs) is linked to excess mortality and haemocompatibility-related events. Whether this association persists with the fully magnetically levitated HeartMate 3 (HM3) pump is unknown. This analysis tested outcomes with obesity and the additive influence of co-existing frailty (‘frail obesity’) in the contemporary era. Methods The study pooled 2200 HM3 recipients from the MOMENTUM 3 pivotal randomized trial (n = 515) and Continued Access Protocol (n = 1685). Obesity was defined as body mass index (BMI) ≥30 kg/m2 and frailty by a 40-item Rockwood cumulative-deficit frailty index (FI), with clinically relevant frailty defined as FI ≥0.325 (moderate–severe frailty); BMI was excluded from the FI to avoid mathematical coupling. The primary endpoint was survival to transplant, recovery, or 24 months of support free of disabling stroke (modified Rankin score >3) or pump replacement reoperation. Results Obese patients (n = 887, 40.3%) were younger, less often with ischaemic aetiology, and more frequently women, but more often had diabetes and hypertension, than non-obese patients. Unadjusted 2-year outcomes were similar between groups (freedom from the primary endpoint: 75.1% vs 77.1%, log-rank P = .34; survival: 79.9% vs 81.2%, P = .57). After covariate adjustment, obesity was independently associated with a higher risk of the primary endpoint (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.07–1.58) and all-cause mortality (HR 1.35, 95% CI 1.10–1.67), as well as heart failure hospitalization, infection, and arrhythmia, but not stroke, bleeding, or early right heart failure. Frailty affected 67.3% of obese recipients (571/849) and was associated with a higher adjusted risk of the primary endpoint (HR 1.51, 95% CI 1.09–2.10), overall mortality and non-haemocompatibilty-related morbidity endpoints. The obesity-by-frailty interaction was not significant for either the primary endpoint (P = .436) or mortality (P = .215), indicating additive rather than synergistic risk; frail–obese patients nonetheless carried the highest absolute risk of any subgroup. Frailty improved by at least one severity class by 6 months in 75.9% of frail–obese patients, and improvement was associated with better survival (adjusted HR 0.14, 95% CI 0.07–0.26). Conclusions In the HM3 era, obese and non-obese recipients had similar unadjusted 2-year outcomes; however, after adjustment for baseline case-mix, obesity was independently associated with a higher risk of both the primary endpoint and all-cause mortality, together with heart failure hospitalization, infection, and arrhythmia. Frailty was independently associated with adverse outcomes across nearly all endpoints and was highly prevalent among obese recipients; the combination of obesity and frailty was additive but not synergistic, with frail–obese patients carrying the highest absolute risk. Frailty, however, proved substantially reversible after LVAD support, and its improvement was associated with markedly better survival. Obesity and frailty should therefore be assessed together, rather than through BMI thresholds alone, with recognition that frailty status is dynamic after implantation and that improvement in frailty is associated with markedly better survival.