Wülfers, Eike M; Moss, Robin; Lehrmann, Heiko; Arentz, Thomas; Westermann, Dirk; Seemann, Gunnar; Odening, Katja E; Steinfurt, Johannes (2024). Whole-heart computational modelling provides further mechanistic insights into ST-elevation in Brugada syndrome. International Journal of Cardiology. Heart & Vasculature, 51(101373) Elsevier 10.1016/j.ijcha.2024.101373
|
Text
1-s2.0-S2352906724000393-main.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
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 (Ito) in the same region. Additionally, a reduction in the fast sodium current (INa) 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 Ito simulations showed early repolarization in the RVOT with a descending but not coved-type ST-elevation. Reduced INa 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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology 04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology |
UniBE Contributor: |
Odening, Katja Elisabeth |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2352-9067 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Mar 2024 13:18 |
Last Modified: |
11 Mar 2024 14:02 |
Publisher DOI: |
10.1016/j.ijcha.2024.101373 |
PubMed ID: |
38464963 |
Uncontrolled Keywords: |
Brugada Computational modeling Depolarization Repolarization ST-elevation |
BORIS DOI: |
10.48350/194116 |
URI: |
https://boris.unibe.ch/id/eprint/194116 |
Actions (login required)
 |
Edit item |