Modeling Idiopathic Ventricular Fibrillation Using iPSC Cardiomyocytes and Computational Approaches: A Proof-of-Concept Study

JACC Clin Electrophysiol. 2024 Sep 3:S2405-500X(24)00711-4. doi: 10.1016/j.jacep.2024.07.014. Online ahead of print.

Abstract

Idiopathic ventricular fibrillation (IVF) is an unrefined diagnosis representing a heterogeneous patient group without a structural or genetic definition. IVF treatment is not mechanistic-based due to the lack of experimental patient-models. We sought to create a methodology to assess cellular arrhythmia mechanisms for IVF as a proof-of-concept study. Using IVF patient-specific induced pluripotent stem cell-derived cardiomyocytes, we integrate electrophysiological optical mapping with computational modeling to characterize the cellular phenotype. This approach flips the traditional paradigm using a biophysically detailed computational model to solve the problem inversely. Insight into the cellular mechanisms of this patient's IVF phenotype could also serve as a therapeutic testbed.

Keywords: cardiac arrhythmia; idiopathic ventricular fibrillation; patient-specific stem cells; ventricular fibrillation.

Publication types

  • Review