Open AccessAssessment of arrhythmia mechanism and burden of the infarcted ventricles following remuscularization with pluripotent stem cell-derived cardiomyocyte patches using patient-derived models
Author(s) -
Joseph Kwong-Leung Yu,
Jialiu A. Liang,
William H. Franceschi,
Qinwen Huang,
Farhad Pashakhanloo,
Eric Sung,
Patrick Boyle,
Natalia A. Trayanova
Publication year - 2021
Publication title -
cardiovascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.774
H-Index - 219
eISSN - 1755-3245
pISSN - 0008-6363
DOI - 10.1093/cvr/cvab140
Subject(s) - induced pluripotent stem cell , cardiology , medicine , magnetic resonance imaging , heart failure , myocardial infarction , radiology , biology , biochemistry , embryonic stem cell , gene
Direct remuscularization with pluripotent stem cell-derived cardiomyocytes (PSC-CMs) seeks to address the onset of heart failure post-myocardial infarction (MI) by treating the persistent muscle deficiency that underlies it. However, direct remuscularization with PSC-CMs could potentially be arrhythmogenic. We investigated two possible mechanisms of arrhythmogenesis-focal vs. re-entrant-arising from direct remuscularization with PSC-CM patches in two personalized, human ventricular computer models of post-MI. Moreover, we developed a principled approach for evaluating arrhythmogenicity of direct remuscularization that factors in the VT propensity of the patient-specific post-MI fibrotic substrate and use it to investigate different conditions of patch remuscularization.