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

BACKGROUND: The AAMS open-label clinical study demonstrated the safety and feasibility of epicardial transplantation of autologous right atrial appendage micrografts (AAMs) during coronary artery bypass grafting (CABG) surgery. The study also provided the first indications of therapeutic efficacy of the AAMs, as delivered within an extracellular matrix patch, to reduce ischemic scar and increase viable ventricular wall thickness. 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 disease (IHD) and myocardial scar, the AAMS2 trial aims to generate state-of-the-art structural and functional imaging data of the myocardium treated with an AAMs-patch during CABG. METHODS: The AAMS2 trial recruits IHD patients who are set to undergo non-urgent CABG and present with an ischemic myocardial scar in preoperative cardiac magnetic resonance imaging (CMRI) with late gadolinium enhancement. Patients are randomized (1:1) to receive a collagen-based matrix patch (Hemopatch®), with or without AAMs, epicardially onto the scar border. The primary endpoint, assessed by CMRI preoperatively and at 6 months post-operative follow-up, focuses on the left ventricle scar mass. The secondary endpoints center on the change in scar mass by the AAMs-patch site and evaluation of therapy safety and feasibility as well as its effects on myocardial structure and function by echocardiography. Change in blood N-terminal-pro-BNP levels in the timeframe is the co-primary endpoint. DISCUSSION: Data from the AAMS2 trial provides the first randomized, blinded, and placebo-controlled evaluation of efficacy on epicardial AAMs transplantation for ischemic myocardial scar. This data will pave the road towards rational design of larger AAMs therapeutic efficacy-addressing trial(s). TRIAL REGISTRATION: ClinicalTrials.gov, NCT05632432, registered 30 November 2022, https://clinicaltrials.gov/study/NCT05632432 .