Whole-heart Computational Modelling Provides Further Mechanistic Insights into ST-elevation in Brugada Syndrome

Overview

Journal Int J Cardiol Heart Vasc

Date 2024 Mar 11

PMID 38464963

Authors

Eike M Wulfers

Robin Moss

Heiko Lehrmann

Thomas Arentz

Dirk Westermann

Gunnar Seemann

Katja E Odening

Johannes Steinfurt

Affiliations

Soon will be listed here.

Abstract

Background: Brugada syndrome (BrS) is characterized by dynamic ST-elevations in right precordial leads and increased risk of ventricular fibrillation and sudden cardiac death. As the mechanism underlying ST-elevation and malignant arrhythmias is controversial computational modeling can aid in exploring the disease mechanism. Thus we aim to test the main competing hypotheses ('delayed depolarization' vs. 'early repolarization') of BrS in a whole-heart computational model.

Methods: In a 3D whole-heart computational model, delayed epicardial RVOT activation with local conduction delay was simulated by reducing conductivity in the epicardial RVOT. Early repolarization was simulated by instead increasing the transient outward potassium current (I) in the same region. Additionally, a reduction in the fast sodium current (I) was incorporated in both models.

Results: Delayed depolarization with local conduction delay in the computational model resulted in coved-type ST-elevation with negative T-waves in the precordial surface ECG leads. 'Saddleback'-shaped ST-elevation was obtained with reduced substrate extent or thickness. Increased I simulations showed early repolarization in the RVOT with a descending but not coved-type ST-elevation. Reduced I did not show a significant effect on ECG morphology.

Conclusions: In this whole-heart BrS computational model of both major hypotheses, realistic coved-type ECG resulted only from delayed epicardial RVOT depolarization with local conduction delay but not early repolarizing ion channel modifications. These simulations provide further support for the depolarization hypothesis as electrophysiological mechanism underlying BrS.

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