iPSC-Derived Heart Cells Show Early Promise in Chinese Heart Failure Trial

Key Points

• The HEAL-CHF trial compared iPSC-derived cardiomyocyte injections plus coronary artery bypass grafting with bypass surgery alone in 20 patients with advanced heart failure.
• Cell therapy produced significantly greater improvements in six-minute walking distance, myocardial perfusion and relative wall thickening.
• The study found no significant between-group differences in ejection fraction, ventricular volumes, myocardial scar size or several other clinical measures.
• No sustained ventricular tachycardia or tumor formation was observed during the study’s defined safety periods, although all 10 cell therapy recipients developed early ventricular arrhythmias.

HELP Therapeutics and researchers at Nanjing Drum Tower Hospital have published results from the HEAL-CHF trial, an early-stage randomized study evaluating allogeneic human induced pluripotent stem cell (iPSC)-derived cardiomyocytes in patients with advanced heart failure.

The study enrolled 20 patients with a left ventricular ejection fraction of 45% or less. Ten received cardiomyocyte injections directly into the heart during coronary artery bypass grafting, while 10 underwent bypass surgery alone.

Efficacy Findings

At 12 months, secondary efficacy analyses found significantly greater improvements with cell therapy in:

• Six-minute walking distance
• Global myocardial perfusion
• Relative wall thickening

The researchers reported that cell transplantation produced “significantly greater improvements in 6-min walk distance” compared with bypass surgery alone.

However, significant differences were not observed between the groups in:

• Left ventricular ejection fraction
• Left ventricular volumes
• Myocardial scar size
• New York Heart Association functional class
• Minnesota Living with Heart Failure Questionnaire scores

Arrhythmias Remain a Safety Question

The trial’s primary endpoint focused on sustained ventricular tachycardia between one and six months after surgery and tumor formation through 12 months. Neither was observed.

Early arrhythmias were common, however. All 10 patients receiving cardiomyocytes developed accelerated idioventricular rhythm during the first four weeks, generally beginning five to seven days after transplantation.

Two patients developed clinically significant ventricular tachycardia above 140 beats per minute. The events peaked two to three weeks after treatment and resolved following cardioversion.

The researchers concluded that future studies will need to determine the risk-to-benefit ratio of iPSC-derived cardiomyocyte therapy given the observed arrhythmias.

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