Early left ventricular unloading after extracorporeal membrane oxygenation: rationale and design of EARLY‐UNLOAD trial

Abstract

Aims The clinical benefits of venoarterial extracorporeal membrane oxygenation (VA‐ECMO) for profound cardiogenic shock are well known. However, peripheral VA‐ECMO increases the left ventricular afterload, thus compromising myocardial recovery. Recent studies have revealed the benefit of left ventricular unloading using various methods applied at different times. The EARLY‐UNLOAD trial compares the clinical outcomes of early left ventricular unloading and conventional approach after VA‐ECMO. Methods and results The EARLY‐UNLOAD trial is a single‐centre, open‐label, randomized trial that recruited 116 patients with cardiogenic shock undergoing VA‐ECMO. Patients meeting the inclusion criteria were randomized in a 1:1 ratio to two groups: routine left ventricular unloading via intracardiac echocardiography‐guided transseptal left atrial cannulation within 12 h of VA‐ECMO initiation or conventional approach that indicates rescue left ventricular unloading if clinical signs of an increased left ventricular afterload are present. The primary endpoint is the cumulative incidence of all‐cause death within 30 days, and patients will be followed‐up for 12 months. A key secondary endpoint is a composite measure of all‐cause death and rescue transseptal left atrial cannulation in the conventional group (suggestive of VA‐ECMO treatment failure) within 30 days. The enrolment of patients was finished in September 2022. Conclusions The EARLY‐UNLOAD trial is the first randomized controlled trial to compare early left ventricular unloading and conventional approach after VA‐ECMO using the same unloading modality. The results could impact clinical practice to overcome the haemodynamic issues associated with VA‐ECMO.

Early Left Ventricular Unloading or Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: The EARLY-UNLOAD Randomized Clinical Trial

“…The trial design has been published previously. 18 The 30-day follow-up for analysis of the primary outcome was completed on October 15, 2022. However, follow-up for the primary analysis continued for up to 6 months after randomization (March 14, 2022) to evaluate in-hospital outcomes, including the rate of heart transplantation.…”

Left Ventricular Unloading in Extracorporeal Membrane Oxygenation: A Clinical Perspective Derived from Basic Cardiovascular Physiology

“…Two recent trials (EVOLVE-ECMO [ 47 ], and EARLY UNLOAD [ 48 ]) investigated the effects of trans-septal cannulation of the left atrium and consequent venting. EVOLVE-ECMO randomized 60 V-A ECMO supported patients with signs of left ventricular overload to early venting through a trans-septally placed cannula in the left atrium within a median 2.4 h after V-A ECMO initiation versus an approach without initial venting.…”

“…Although there was no survival benefit, a significantly larger number of patients in the control arm developed pulmonary edema and nearly 80 percent of them eventually received left atrial venting [ 47 ]. EARLY UNLOAD was a single center study which was set out to find out whether venting through trans-septal cannulation would result in a 25 percent absolute mortality reduction at 30 days [ 48 ]. For this purpose, 116 patients with cardiogenic shock were randomized in a 1:1 fashion to left ventricular unloading through percutaneous trans-septal cannulation within 12 h after V-A ECMO initiation versus conventional therapy.…”