Autologous atrial appendage micrografts transplanted during coronary artery bypass surgery: design of the AAMS2 randomized, double-blinded, and placebo-controlled trial

Abstract

Background—The AAMS open-label clinical study demonstrated safety and feasibility of epicardial transplantation of autologous right atrial appendage micrografts (AAMs) during coronary artery bypass grafting (CABG) surgery. Delivered in an extracellular matrix patch, the study also provided first indications of reduced ischemic scar and increased live ventricular wall thickness associated with AAMs therapy. To further evaluate the initial beneficial effects observed in the AAMS study, we designed the randomized, double-blinded, and placebo-controlled AAMS2 trial. Focusing on patients with ischemic heart failure with reduced ejection fraction (iHFrEF), the AAMS2 trial aims to generate state-of-the-art structural and functional imaging data on the myocardium treated with an AAMs-patch during CABG. Methods—The AAMS2 trial recruits iHFrEF patients who are set to undergo non-urgent CABG and present with a myocardial scar in preoperative cardiac magnetic resonance (CMR) with late gadolinium enhancement. Patients are randomized evenly (1:1) to receive an collagen-based matrix patch (Hemopatch^®), with or without AAMs, epicardially onto the scar border. The primary endpoints at 6 months post-operatively are the effect change on the myocardial scar size by the AAMs-patch transplantation site, as assessed by CMR with late gadolinium enhancement and change in blood N-terminal-pro-BNP in the timeframe. The trial’s secondary endpoints address feasibility, safety, echocardiography, quality of life, symptom scaling, and 6-minute walk test. Discussion—Data from the AAMS2 trial provide the first randomized, blinded, and placebo-controlled evaluation of efficacy on epicardial AAMs transplantation for iHFrEF. This data then enables the rational design of larger AAMs therapeutic efficacy-addressing trial(s). Trial Registration: ClinicalTrials.gov, NCT05632432, registered 30 November 2022, https://clinicaltrials.gov/study/NCT05632432