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

BACKGROUND: Intramyocardial injection of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising cell replacement therapy for myocardial infarction, but engraftment arrhythmias (EAs) posttransplantation hinder their clinical translation. OBJECTIVE: This study aims to analyze EA characteristics after hiPSC-CM transplantation and to identify risk factors associated with the occurrence of EAs. METHODS: cells). EA characteristics were analyzed and compared between the 2 subgroups. Univariate logistic regression was performed to identify risk factors for EAs. RESULTS: A total of 24 patients in the experimental group were enrolled, 13 (54.2%) of whom developed EAs originating from the cell injection site (localized by electrocardiogram QRS morphology). Initially, EAs were paroxysmal (heart rate: 55-96 bpm, 72.15 ± 9.77 bpm), progressing to sustained episodes over hours with increased heart rate (max 111-185 bpm, 146.00 ± 21.02 bpm) and R-R interval variability. No hemodynamic abnormalities were detected in any patient during EA episodes. Atrial pacing and electrical cardioversion reduced EA rate but failed to terminate EAs. EA incidence was significantly higher in the high-dose than low-dose group (10/12 [83.3%] vs 3/12 [25.0%], P = .012). Univariate logistic regression showed hiPSC-CM dose was significantly associated with EA occurrence (odds ratio, 15.00; 95% confidence interval, 2.02-111.17; P = .008). CONCLUSION: The occurrence of EAs was likely driven by an automaticity mechanism, and hiPSC-CM transplantation dose was significantly correlated with EA incidence.