Transvalvular Unloading Mitigates Ventricular Injury Due to Venoarterial Extracorporeal Membrane Oxygenation in Acute Myocardial Infarction

•Transvalvular unloading with VA-ECMO (EC-Pella) is being used in patients with AMI.•VA-ECMO increases IS despite reducing LV work while EC-Pella reduces IS and LV work.•Cardioprotective signaling is activated with EC-Pella, not VA-ECMO.•EC-Pella fails to rescue mitochondrial injury due to VA-ECMO.•Load independent myocardial injury mechanisms due to VA-ECMO may be targets in AMI.