Whole-heart computational modelling provides further mechanistic insights into ST-elevation in Brugada syndrome.

Int J Cardiol Heart Vasc

Department of Cardiology and Angiology, University Heart Center Freiburg - Bad Krozingen, and Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Published: April 2024

AI Article Synopsis

  • Brugada syndrome (BrS) is associated with abnormal heart rhythms, particularly ST-elevations in specific leads, increasing the risk of sudden cardiac death, and understanding its mechanisms can be aided by computational modeling.
  • Researchers tested two main hypotheses—'delayed depolarization' and 'early repolarization'—using a 3D whole-heart computational model that simulated different ionic changes affecting the heart's electrical activity.
  • Results showed that realistic coved-type ST-elevation, characteristic of BrS, was only produced by delayed epicardial depolarization, supporting the depolarization hypothesis and suggesting early repolarization does not play a significant role in the ECG changes observed in BrS.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924145PMC
http://dx.doi.org/10.1016/j.ijcha.2024.101373DOI Listing

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