Epicardial Injections of Allogenic Human Induced Pluripotent Stem Cells-derived Cardiomyocytes for Severe Chronic Ischemic Heart Failure: The HEAL-CHF Trial

Abstract Heart failure continues to impose a significant global health burden, with a continuous search for therapies capable of promoting a true myocardial regeneration. The HEAL-CHF trial evaluated the safety and efficacy of intramyocardial injections of allogeneic human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in advanced heart failure (LVEF≤45%) patients with concomittent coronary artery bypass grafting (CABG). The primary safety endpoints, defined as the incidence of sustained ventricular arrhythmias at 1-6-month follow-up and tumorigenicity at 12-month follow-up, were not observed. Efficacy analyses suggested benefits of cell transplantation compared with CABG alone, primarily evidenced by significant improvements in 6-minute walk distance (6MWD), stroke volume (SV), myocardial perfusion recovery and myocardial contractility. This first randomized and controlled clinical trial of human iPSC-based cardiac regenerative therapy demonstrates the safety and therapeutic potential of hiPSC-CMs and provides a strong incentive for moving to trials adequately powered to yield robust efficacy data. (ClinicalTrials.gov registration: NCT03763136.)