UNLOAD-ECMO Randomised Controlled Trial for Left Ventricular Unloading with Veno-arterial Extracorporeal Membrane Oxygenation in Severe Cardiogenic Shock

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Dr Schrage opened his presentation by recapping that veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides circulatory support for cardiogenic shock (CS), but also increases left ventricular (LV) afterload, which can hamper myocardial recovery. In a recent multinational multicentre retrospective registry study, it was shown that if the LV afterload is reversed by active LV unloading using Impella in addition to VA-ECMO in the setting of CS, 30-day mortality was lower, although there were higher rates of complications, such as bleeding and ischaemia.1

Based on learnings from this data, Dr Schrage and his team designed a randomised clinical trial, the UNLOAD-ECMO trial, to test the hypothesis that active LV loading with Impella combined with VA-ECMO (ECPella strategy) improves 30-day survival in patients with severe CS compared with the strategy of VA-ECMO alone. The study population consists of patients with severe CS due to severe LV dysfunction. These patients will be randomised 1 : 1 to either the intervention arm for treatment with an Impella for active LV unloading on top of VA-ECMO (n=99) or the control arm with VA-ECMO alone (n=99). A blinded interim analysis will be performed after enrolment of 75% (n=148) of patients is achieved. The primary endpoint of the study is time to death from any cause within 30 days after randomisation; data from a 12-month follow-up for additional secondary efficacy endpoints and safety endpoints will also be collected.

Dr Schrage highlighted that the trial includes patients with a number of key inclusion features. First, an arterial lactate concentration of >5 mmol/l, which is a higher threshold than previous randomised controlled trials on mechanical circulatory support, has been included to target a high-risk patient population and distinguish patients with high mortality even within the same Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK stage.2 A second key inclusion criterion is systolic blood pressure <90 mmHg or the need for catecholamines to maintain blood pressure at this level. In addition, patients must display the signs of impaired organ perfusion with at least one of the following: impaired mental status or cold, clammy skin or oliguria with urine output <30 ml/h. Third, it has been decided to include patients who have undergone previous ECMO therapy for up to 6 hours before implantation of the Impella device, and a resuscitation time of up to 60 minutes is allowed. Finally, the study will include patients with both acute MI-CS and non-acute MI-CS because there appears to be no association between causes of CS and mortality after VA-ECMO. The trial encourages early active LV unloading by early implantation of Impella and early explant in accordance with strict protocols. Due to the risk of complications arising from the use of two devices simultaneously, study procedures encourage the use of ultrasound-guided access and micropuncture sets to assist with device implantation. Dr Schrage clarified that at the present time the trial does not rely upon any objective criteria for LV dysfunction.

Dr Schrage closed his presentation by announcing that enrolment is expected to commence imminently.


  1. Schrage B, Becher PM, Bernhardt A, et al. Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: results from an international, multicenter cohort study. Circulation 2020;142(22):2095–106. 
    Crossref | Pubmed
  2. Jentzer JC, Schrage B, Patel PC, et al. Association between the acidemia, lactic acidosis, and shock severity with outcomes in patients with cardiogenic shock. J Am Heart Assoc 2022;11:e024932. 
    Crossref | Pubmed