Left ventricular unloading during VA-ECMO for refractory cardiogenic shock: a target trial emulation multicenter analysis

BACKGROUND: Conflicting data exist regarding the survival benefit of mechanical left ventricular (LV) unloading in patients receiving peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock (CS). In this study, we aimed to assess the effect of LV unloading (Impella or intra-aortic balloon pump [IABP]) on 60-day mortality in patients with refractory CS treated with VA-ECMO. METHODS: We conducted a retrospective bi-center study including consecutive patients requiring VA-ECMO for ≥ 48 h in two high-volume ECMO centers between 2019 and 2023, using the target trial emulation framework. Patients were classified as receiving VA-ECMO alone or VA-ECMO with LV unloading if the unloading strategy was applied within 24 h after ECMO implantation. Propensity-score overlap weighting was applied to adjust for baseline differences. The primary endpoint was 60-day mortality. Secondary outcomes included ECMO weaning rates and device-related complications. RESULTS: Among 264 patients (76% male, mean age 53 ± 14 years), 138 (52.2%) received VA-ECMO alone and 126 (47.8%) underwent LV unloading (78 IABP, 48 Impella), 2 were lost to follow-up. Unloading was not associated with improved 60-day mortality (weighted risk difference: 1.4% [95% CI: -11.8%, 14.6%], p = 0.84). No significant differences were observed in ECMO weaning rates, but device-related complications were more frequent in the unloading group. CONCLUSION: In this propensity-score weighted analysis, LV unloading during VA-ECMO was not associated with improved survival at 60 days. These hypothesis-generating findings highlight the need for a refined, phenotype-driven approach to patient selection for LV unloading in ECMO-supported cardiogenic shock.