Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used for refractory cardiogenic shock, yet optimal weaning strategies and the role of left ventricular (LV) venting remain unclear. The TWEET-1 study was designed as an early feasibility investigation to define processes, timelines, and clinical parameters for future interventional trials evaluating Impella 5.5 for LV venting during V-A ECMO support.

This prospective, single-center observational study from 2021 to 2025 included patients who received standard-of-care V-A ECMO and Swan-Ganz monitoring. Patients were assigned to the ECPELLA + group (defined as the addition of Impella 5.5 to V-A ECMO to provide left ventricular unloading) when pulmonary artery (PA) diastolic pressure exceeded 20 mm Hg; other individuals served as controls. The primary outcome was survival to discharge. Secondary outcomes included V-A ECMO duration, complications, and SAVE score–adjusted survival.

Among 117 screened patients, 43 were enrolled (25 ECPELLA +, 18 controls). Overall survival to discharge was 53% with no significant difference between groups. ECPELLA + patients had higher pulmonary pressures and longer V-A ECMO support but demonstrated appropriate selection for unloading. Both groups exceeded the SAVE score–predicted survival. Subgroup analysis suggested potential benefit of Impella venting in the most severe patients (SAVE −14 to −10).

Hemodynamic-guided LV venting with Impella 5.5 during V-A ECMO was feasible and enabled prompt LV unloading (ECPELLA). While survival to discharge did not differ significantly between groups, patients with higher PA diastolic pressures and SAVE scores below −10 demonstrated a significant reduction in mortality with LV unloading.

Early hemodynamic-guided LV unloading may improve risk-adjusted V-A ECMO outcomes.