Modelling and Simulation Reveals Density-Dependent Re-Entry Risk in The Infarcted Ventricles After Stem Cell-Derived Cardiomyocyte Delivery

2022 Computing in Cardiology (CinC) Pub Date : 2022-09-04 DOI:10.22489/CinC.2022.392

Leto L. Riebel, Z. Wang, H. Martinez-Navarro, C. Trovato, J. Biasetti, R. S. Oliveira, R. D. Santos, Blanca A Rodríguez

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Abstract

Delivery of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a potential therapy to improve cardiac function after injury. However, hPSCCMs express immature electrophysiological and structural properties and may be pro-arrhythmic. Our goal is to identify key factors determining arrhythmic risk of hPSC-CM therapy in the infarcted human ventricles through modelling and simulation. We model three densities of hPSC-CMs covering 4%, 22%, and 39% of the infarct and border zone and induce re-entry through ectopic stimulation. We furthermore simulate the effect of different therapeutic agents on re-entry susceptibility. Due to the increased refractory period of the hPSC-CMs, the vulnerable window increases from 20ms in control, to 60ms in the low- and 80ms in the medium- and high-density scenarios. Our results highlight the density-dependent effect of hPSC-CM delivery on arrhythmic risk after myocardial infarction and show the effect of therapeutic strategies on this increased re-entry susceptibility.

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模型和模拟揭示了干细胞衍生心肌细胞输送后梗死心室的密度依赖性再入风险

人多能干细胞来源的心肌细胞(hPSC-CMs)是一种改善损伤后心功能的潜在治疗方法。然而，hpsccm表达不成熟的电生理和结构特性，可能会导致心律失常。我们的目标是通过建模和模拟来确定确定hPSC-CM治疗梗死人类心室心律失常风险的关键因素。我们模拟了三种hPSC-CMs密度，分别覆盖4%、22%和39%的梗死区和边界区，并通过异位刺激诱导其重新进入。我们进一步模拟了不同治疗剂对再入易感性的影响。由于hPSC-CMs的不应期增加，脆弱窗口从对照组的20ms增加到低剂量的60ms，中剂量和高密度的80ms。我们的研究结果强调了hPSC-CM递送对心肌梗死后心律失常风险的密度依赖性作用，并显示了治疗策略对这种增加的再进入易感性的影响。

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2022 Computing in Cardiology (CinC)

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