Regenerative strategies for heart failure aim to restore myocardial tissue and improve function. This early-stage randomized trial, HEAL-CHF, tested intramyocardial delivery of allogeneic human induced pluripotent stem cell-derived cardiomyocytes in patients with advanced ischemic heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%). All participants underwent coronary revascularization at the time of intervention to standardize surgical care across groups.
HEAL-CHF enrolled a total of 20 participants (18 male, 2 female) with advanced ischemic heart failure and randomized them to receive either intramyocardial cell injection plus concomitant coronary artery bypass grafting or CABG alone. The report indicates that 10 patients received the cell therapy and 10 were uninjected controls undergoing the same revascularization procedure. The trial was intended as an early-stage safety and feasibility evaluation rather than a definitive efficacy trial. ClinicalTrials.gov registration is cited (NCT03763136).
The prespecified primary safety endpoint combined two outcomes: incidence of sustained ventricular tachycardia during the 1- to 6-month postoperative period, and evidence of tumorigenicity at 12 months. Across both randomized groups, neither sustained ventricular tachycardia in months 1–6 nor tumor formation at 12 months was observed. These findings indicate that no sustained VT meeting the primary safety definition or detectable neoplastic growth was recorded during the trial follow-up period reported.
Despite the absence of the primary sustained VT endpoint, all 10 patients in the cell therapy arm developed early post-transplant ventricular rhythm disturbances. Specifically, each of these patients experienced accelerated idioventricular rhythm (AIVR), which typically emerged 5–7 days after transplantation and occurred within the first 4 weeks. In addition, two patients in the cell group developed clinically significant ventricular tachycardia (defined in the report as >140 beats per minute). These episodes peaked at 2–3 weeks post-procedure and resolved completely after cardioversion.
These observations highlight a pattern of early transient arrhythmias after intramyocardial injection of pluripotent stem cell–derived cardiomyocytes: frequent, self-limited AIVR and occasional sustained high-rate VT requiring intervention. The authors note that these arrhythmic events will necessitate careful assessment of the risk-to-benefit ratio in future studies.
Secondary analyses examined functional capacity and imaging measures. Patients receiving cell transplantation achieved significantly greater improvements in 6-minute walk distance compared with CABG alone. Imaging-based secondary endpoints also favored the cell group for some measures: global myocardial perfusion, assessed by the summed rest score on 99mTc single-photon emission computed tomography–computed tomography (SPECT–CT), and relative wall thickening showed significantly greater improvement in the transplant group.
However, at 12 months there were no significant between-group differences in several key clinical and structural outcomes, including left ventricular ejection fraction, left ventricular volumes, myocardial scar size, New York Heart Association (NYHA) functional class, or Minnesota Living with Heart Failure Questionnaire scores. Thus, benefits were present for some functional and perfusion metrics but not for conventional measures of global systolic function or quality-of-life indices at one year.
The trial included quantitative imaging endpoints, illustrated in the published figures and extended data. Global myocardial perfusion was evaluated by summed rest score on 99mTc SPECT–CT, and relative wall thickening was measured as a regional functional metric. These imaging assessments contributed to the finding that the cell therapy group experienced improved perfusion and wall motion recovery relative to CABG alone. Detailed numeric values and statistical parameters are presented in the article’s figures and extended data tables; interested readers should consult the source for exact values.
The authors state that supporting data are provided within the Article, Extended Data Tables and Figures, Supplementary Information and Source Data. Additional de-identified participant-level data may be shared with qualified researchers on reasonable request, subject to ethical approvals, participant consent, sponsor and institutional governance review, and an appropriate data use or transfer agreement. The report explains that individual-level public release was not planned because the small, single-center trial and combination of clinical, imaging and safety data pose a re-identification risk.
Limitations inherent to the trial include its small sample size, single-center early-stage design and the focus on safety and feasibility rather than definitive efficacy. These constraints limit generalizability and statistical power for many efficacy endpoints.
In this early randomized study of intramyocardial allogeneic iPSC-derived cardiomyocytes administered at the time of CABG in patients with advanced ischemic HFrEF, the prespecified primary safety outcomes—sustained ventricular tachycardia between months 1–6 and tumorigenicity at 12 months—were not observed. All patients in the cell arm experienced early transient accelerated idioventricular rhythm, and two developed clinically significant ventricular tachycardia that resolved after cardioversion. Secondary analyses indicated improved 6-minute walk distance, myocardial perfusion and relative wall thickening with cell therapy, but no differences were detected for LVEF, volumes, scar size or several clinical outcome measures at 12 months.
The pattern of early arrhythmias indicates a need for rigorous arrhythmia monitoring and mechanistic investigation in future studies, and for careful evaluation of the overall risk–benefit profile before broader clinical application. Further larger, multicenter trials with longer follow-up will be required to define efficacy, durability and safety of intramyocardial allogeneic iPSC-derived cardiomyocyte therapy for ischemic heart failure.
ClinicalTrials.gov registration: NCT03763136.