Theoretical prediction of early afterdepolarization-evoked triggered activity formation initiating ventricular reentrant arrhythmias

Kunichika Tsumoto; Takao Shimamoto; Yuma Aoji; Yukiko Himeno; Yuhichi Kuda; Mamoru Tanida; Akira Amano; Yasutaka Kurata

doi:10.1016/j.cmpb.2023.107722

Theoretical prediction of early afterdepolarization-evoked triggered activity formation initiating ventricular reentrant arrhythmias

Comput Methods Programs Biomed. 2023 Oct:240:107722. doi: 10.1016/j.cmpb.2023.107722. Epub 2023 Jul 15.

Authors

Kunichika Tsumoto¹, Takao Shimamoto², Yuma Aoji², Yukiko Himeno², Yuhichi Kuda³, Mamoru Tanida³, Akira Amano², Yasutaka Kurata⁴

Affiliations

¹ Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan. Electronic address: tsumoto@kanazawa-med.ac.jp.
² Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan.
³ Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan.
⁴ Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan. Electronic address: yasu@kanazawa-med.ac.jp.

PMID: 37515880
DOI: 10.1016/j.cmpb.2023.107722

Abstract

Background and objective: Excessive prolongation of QT interval on ECGs in patients with congenital/acquired long QT syndrome and heart failure is a sign suggesting the development of early afterdepolarization (EAD), an abnormal repolarization in the action potential of ventricular cardiomyocytes. The development of EAD has been believed to be a trigger for fatal tachyarrhythmia, which can be a risk for sudden cardiac death. The role of EAD in triggering ventricular tachycardia (VT) remains unclear. The aim of this study was to elucidate the mechanism of EAD-induced triggered activity formation that leads to the VT such as Torsades de Pointes.

Methods: We investigated the relationship between EAD and tachyarrhythmia initiation by constructing homogeneous myocardial sheet models consisting of the mid-myocardial cell version of a human ventricular myocyte model and performing simulations of excitation propagation.

Results: A solitary island-like (clustering) occurrence of EADs in the homogeneous myocardial sheet could induce a focal excitation wave. However, reentrant excitation, an entity of tachyarrhythmia, was not able to be triggered regardless of the EAD cluster size when the focal excitation wave formed a repolarization potential difference boundary consisting of only a convex surface. The discontinuous distribution of multiple EAD clusters in the ventricular tissue formed a specific repolarization heterogeneity due to the repolarization potential difference, the shape of which depended on EAD cluster size and placed intervals. We found that the triggered activity was formed in such a manner that the repolarization potential difference boundary included a concave surface.

Conclusions: The formation of triggered activity that led to tachyarrhythmia required not only the occurrence of EAD onset-mediated focal excitation wave but also a repolarization heterogeneity-based specific repolarization potential difference boundary shape formed within the tissue.

Keywords: Early afterdepolarization; Excitation propagation; Reentrant tachyarrhythmias; Repolarization heterogeneity; Triggered activity.

MeSH terms

Action Potentials
Arrhythmias, Cardiac
Electrocardiography
Heart Ventricles
Humans
Long QT Syndrome* / diagnosis
Long QT Syndrome* / metabolism
Tachycardia, Ventricular*
Torsades de Pointes*