Intramyocardial injection of allogeneic human induced pluripotent stem cell-derived cardiomyocytes in advanced ischemic heart failure: an early-stage randomized trial.

A treatment for heart failure that could promote myocardial regeneration has long been sought. Here we conduct the HEAL-CHF trial (n = 20; 18 male and 2 female), in which patients with advanced heart failure with reduced ejection fraction (left ventricular ejection fraction ≤45%) were randomized to receive intramyocardial injections of allogeneic human induced pluripotent stem cell-derived cardiomyocytes or were uninjected. Both groups received concomitant coronary artery bypass grafting. The primary endpoint was safety, defined as the incidence of sustained ventricular tachycardia during the 1- to 6-month postoperative period and tumorigenicity at 12 months of follow-up. Neither sustained ventricular tachycardia nor tumorigenicity was observed in either patient group. Early post-transplantation ventricular arrhythmias occurred in patients in the cell therapy group during the first 4 weeks, as all 10 patients in this group developed accelerated idioventricular rhythm, typically emerging 5 to 7 days post-transplantation. Clinically significant ventricular tachycardia (>140 bpm), which occurred in 2 patients, peaked at 2 to 3 weeks post-procedure and resolved completely after cardioversion. Secondary efficacy analyses indicated that cell transplantation provided significantly greater improvements in 6-min walk distance, global myocardial perfusion (as assessed by the summed rest score on 99mTc single-photon emission computed tomography-computed tomography) and relative wall thickening, compared with coronary artery bypass grafting alone. No significant between-group differences were observed for left ventricular ejection fraction, left ventricular volumes, myocardial scar size, New York Heart Association functional class or Minnesota Living with Heart Failure Questionnaire scores at 12 months. In view of the arrhythmic events observed, future studies will need to determine the risk-to-benefit ratio associated with human induced pluripotent stem cell-derived cardiomyocyte therapy. ClinicalTrials.gov registration: NCT03763136 .