Management of engraftment arrhythmias associated with human-induced pluripotent stem cell-derived cardiomyocytes

Aixue Zhang1, Yufan Liu1, Yanwei Wei1

  • 1TEDA International Cardiovascular Hospital, Tianjin University, Tianjin, China.

Heart Rhythm
|July 3, 2026
PubMed

Insights

High-dose human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) transplantation increases the risk of early afterdepolarizations (EAs). Lower doses may mitigate EA occurrence, suggesting dose-dependent safety concerns for cell therapy in myocardial infarction.

Area of Science:

  • Cardiovascular Medicine
  • Regenerative Medicine
  • Stem Cell Therapy

Background:

  • Intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) shows promise for myocardial infarction treatment.
  • Early afterdepolarizations (EAs) occurring post-transplantation pose a significant barrier to the clinical translation of this cell therapy.

Purpose of the Study:

  • To characterize the nature of EAs following hiPSC-CM transplantation.
  • To identify critical risk factors associated with the development of EAs after hiPSC-CM transplantation.

Main Methods:

  • Patients undergoing coronary artery bypass grafting (CABG) with hiPSC-CM transplantation (experimental) or isolated CABG (control) were studied.
  • Experimental group patients received low (0.5×10^8) or high (1.5×10^8) doses of hiPSC-CMs.
  • EA characteristics were analyzed, and univariate logistic regression identified risk factors for EAs.

Main Results:

  • EAs occurred in 54.2% of hiPSC-CM recipients, originating from the injection site.
  • EAs progressed from paroxysmal to sustained episodes with increased heart rate and R-R variability.
  • Higher hiPSC-CM dose significantly correlated with increased EA incidence (83.3% high-dose vs. 25.0% low-dose; P=0.012).

Conclusions:

  • Early afterdepolarizations following hiPSC-CM transplantation appear to be driven by an automaticity mechanism.
  • The dosage of hiPSC-CMs is a significant factor influencing the incidence of EAs, highlighting a dose-dependent risk.
Abstract

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