Early left ventricular unloading with intra-aortic balloon pump versus micro-axial flow pump in cardiogenic shock supported by VA-ECMO: an international observational target trial emulation

Background Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used during refractory cardiogenic shock (CS) but may impede myocardial recovery through increased left-ventricular afterload. Mechanical left ventricular unloading (LVU) with intra-aortic balloon pump (IABP) or micro-axial flow pump (mAFP) may mitigate this effect; However, to date, no randomized trial has compared these strategies. We emulated a target trial to compare early LVU by IABP versus mAFP on myocardial recovery in refractory CS patients supported by V-A ECMO. Methods We analyzed adults with refractory CS from the international ELLIPSE registry (17 centers, 2010–2023) who received V-A ECMO plus mAFP or IABP within 24 hours of V-A ECMO initiation. Time zero was defined as initiation of unloading on top of V-A ECMO to avoid immortal-time bias. The primary endpoint was myocardial recovery at discharge (survival free from death, durable left ventricular assist device or heart transplantation) and at 1 year. Causal effects were estimated via inverse-probability-of-treatment weighting (IPTW). Results Among 1,112 screened patients with V-A ECMO and concomitant LVU, 747 met eligibilities (IABP n=379; mAFP n=368). Before weighting, patients in the V-A ECMO/mAFP group had higher lactate level (7.7 ± 5.6 vs 6.8 ± 5.3 mmol/L; P = 0.023) and lower acute myocardial infarction prevalence (63.0% vs 72.0%; P = 0.009). Myocardial recovery at discharge was significantly higher with V-A ECMO/mAFP (33.4% vs 26.9% %; absolute difference +6.6 percentage points, 95% CI, 3.3–12.8, p = 0.04) and this association remained significant after IPTW (weighted OR 0.76, 95% CI 0.56–0.96). At 1-year, myocardial recovery was significantly higher with V-A ECMO/mAFP, with longer restricted mean event-free survival compared with IABP (137 vs 110 days; absolute difference 26 days, 95% CI 5–52). Bleeding and ischemic complications were similar between groups, whereas renal replacement therapy was more frequent with V-A ECMO/mAFP. Conclusion In this international target-trial emulation, early LVU by mAFP during V-A ECMO was associated with higher myocardial recovery at discharge and sustained recovery at 1 year compared with IABP. These results support early active LVU and provide a rationale for randomized trials.