Wülfers Eike M, Moss Robin, Lehrmann Heiko, Arentz Thomas, Westermann Dirk, Seemann Gunnar, Odening Katja E, Steinfurt Johannes
Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg - Bad Krozingen, and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Physics and Astronomy, Faculty of Sciences, Ghent University, Ghent, Belgium.
Int J Cardiol Heart Vasc. 2024 Mar 4;51:101373. doi: 10.1016/j.ijcha.2024.101373. eCollection 2024 Apr.
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.
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.
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.
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.
Brugada综合征（BrS）的特征是右胸前导联出现动态ST段抬高，以及心室颤动和心源性猝死风险增加。由于ST段抬高和恶性心律失常的潜在机制存在争议，计算建模有助于探索疾病机制。因此，我们旨在在全心脏计算模型中检验BrS的主要相互竞争的假说（“延迟去极化”与“早期复极化”）。
在一个三维全心脏计算模型中，通过降低右心室流出道（RVOT）心外膜的电导率来模拟心外膜RVOT激活延迟和局部传导延迟。通过增加同一区域的瞬时外向钾电流（Ito）来模拟早期复极化。此外，在两个模型中都纳入了快速钠电流（INa）的降低。
计算模型中局部传导延迟的延迟去极化导致胸前体表心电图导联出现穹窿型ST段抬高和负向T波。当基质范围或厚度减小时，可获得“马鞍形”ST段抬高。增加Ito模拟显示RVOT早期复极化，ST段抬高呈下降型而非穹窿型。降低INa对心电图形态无显著影响。
在这个关于两种主要假说的全心脏BrS计算模型中，逼真的穹窿型心电图仅由心外膜RVOT延迟去极化和局部传导延迟导致，而非早期复极化离子通道改变。这些模拟为去极化假说作为BrS的电生理机制提供了进一步支持。
