Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation

Abstract

Brugada syndrome (BrS), early repolarization syndrome (ERS), and idiopathic ventricular fibrillation (iVF) have long been considered primary electrical disorders associated with malignant ventricular arrhythmia and sudden cardiac death. However, recent studies have revealed the presence of subtle microstructural abnormalities of the extracellular matrix in some cases of BrS, ERS, and iVF, particularly within right ventricular subepicardial myocardium. Substrate-based ablation within this region has been shown to ameliorate the electrocardiographic phenotype and to reduce arrhythmia frequency in BrS. Patients with ERS and iVF may also exhibit low-voltage and fractionated electrograms in the ventricular subepicardial myocardium, which can be treated with ablation. A significant proportion of patients with BrS and ERS, as well as some iVF survivors, harbor pathogenic variants in the voltage-gated sodium channel gene, SCN5A, but the majority of genetic susceptibility of these disorders is likely to be polygenic. Here, we postulate that BrS, ERS, and iVF may form part of a spectrum of subtle subepicardial cardiomyopathy. We propose that impaired sodium current, along with genetic and environmental susceptibility, precipitates a reduction in epicardial conduction reserve, facilitating current-to-load mismatch at sites of structural discontinuity, giving rise to electrocardiographic changes and the arrhythmogenic substrate.

Keywords: Brugada syndrome; arrhythmogenic cardiomyopathies; ventricular fibrillation.

Figure 1.

Proposed mechanisms and modulating factors underlying arrhythmogenesis in the subepicardial cardiomyopathy, giving rise to BrS, ERS, and idiopathic VF. ACM indicates arrhythmogenic cardiomyopathy; BrS, Brugada syndrome; ERS, early repolarization syndrome; and VF, ventricular fibrillation.

Figure 2.

Development of LGE on CMR imaging during follow-up in patients with BrS. Four (22%) patients (ATT1, BPS1, BPU1, and BXI1) developed focal septal late gadolinium enhancement (LGE) during assessment with serial cardiac magnetic resonance (CMR). Average time between follow-up imaging was 5.0±1.7 years. BrS indicates Brugada syndrome. Reproduced with permission from Isbister et al. Copyright © 2023 Elsevier.

Figure 3.

Detectability and severity of structural abnormalities in BrS, ERS, and ACM with respect to cardiac diagnostic modalities. ACM indicates arrhythmogenic cardiomyopathy; BrS, Brugada syndrome; ERS, early repolarization syndrome; iVF, idiopathic ventricular fibrillation; and MRI, magnetic resonance imaging. Adapted from Boukens et al with permission. Copyright © 2020 Elsevier.