Heart failure remains a significant cause of morbidity and mortality following myocardial infarction. Cardiac remuscularization with transplantation of human pluripotent stem cell-derived cardiomyocytes is a promising preclinical therapy to restore function. Recent large animal data, however, have revealed a significant risk of engraftment arrhythmia (EA). Although transient, the risk posed by EA presents a barrier to clinical translation. We hypothesized that clinically approved antiarrhythmic drugs can prevent EA-related mortality as well as suppress tachycardia and arrhythmia burden. This study uses a porcine model to provide proof-of-concept evidence that a combination of amiodarone and ivabradine can effectively suppress EA. None of the nine treated subjects experienced the primary endpoint of cardiac death, unstable EA, or heart failure compared with five out of eight (62.5%) in the control cohort (hazard ratio = 0.00; 95% confidence interval: 0–0.297; p = 0.002). Pharmacologic treatment of EA may be a viable strategy to improve safety and allow further clinical development of cardiac remuscularization therapy.

心力衰竭仍然是心肌梗死后发病率和死亡率的重要原因。通过移植人多能干细胞衍生的心肌细胞进行心脏再肌肉化是一种有希望的临床前治疗以恢复功能。然而，最近的大型动物数据揭示了植入性心律失常 (EA) 的显着风险。虽然是短暂的，但 EA 带来的风险对临床转化构成了障碍。我们假设临床批准的抗心律失常药物可以预防 EA 相关的死亡率以及抑制心动过速和心律失常负担。本研究使用猪模型提供概念验证证据，证明胺碘酮和伊伐布雷定的组合可以有效抑制 EA。九名接受治疗的受试者均未经历心源性死亡、不稳定 EA、或心力衰竭，而对照组中有八分之五（62.5%）（风险比 = 0.00；95% 置信区间：0-0.297；p = 0.002）。EA的药物治疗可能是提高安全性并允许心脏再肌肉化治疗进一步临床开发的可行策略。