Identification of the Arrhythmogenic Substrate in Brugada Syndrome: A Computational Study

Brugada syndrome (BrS) is a primarily electrical epicardial disease that increases the risk of sudden cardiac death. Arrhythmic events in BrS originate from the BrS substrate, located in the right ventricular outflow tract. Risk stratification in BrS patients is still controversial, with several models that have been recently proposed, especially for asymptomatic patients. In this contribution, we developed a computational model of the human right ventricle with alterations that represent the BrS substrate. The model is used to study the arrhythmogenic mechanism of BrS and the effect of different electrophysiological alterations on simulated epicardial unipolar electrograms (UEGs). We observed that the presence of diffuse fibrosis and repolarization abnormalities creates reentrant circuits that induce ventricular arrhythmia. Additionally, we found that repolarization and depolarization abnormalities have a similar effect on simulated UEGs, resulting in J/ST elevation. Our results link features observed on UEGs to the electrophysiological condition of the BrS substrate, offering new information that could be useful in risk stratification of BrS patients.