Subepicardial Cardiomyopathy: A Disease
Underlying J-Wave Syndromes and Idiopathic
Brugada syndrome (BrS), early repolarization syndrome (ERS), and idiopathic ventricular fibrillation (iVF) have long been considered pure electrical disorders (i.e. electrical disease in which only the electrical activity is disturbed), associated with life-threatening ventricular arrhythmia and sudden cardiac death. This means that there are no presumed abnormalities in the structure of the heart. However, in recent years there are several studies that have revealed the presence of subtle microstructural abnormalities in some cases of BrS, ERS, and iVF. These subtle abnormalities are particularly found within the outer layers of the right ventricle.
It was first shown in BrS that ablation at the outside (epicardium) of the right ventricular outflow part is able to normalize the ECG and to reduce arrhythmia frequency. In the area where the ablation is performed abnormal electrical signals are found (i.e. so-called low-voltage showing a a decreased height of the QRS complex from the lowest to the highest point of the ECG spike, and fractionated electrograms showing additional waves or notches in the QRS complex). Patients with ERS and iVF may also exhibit similar abnormal electrical activity in the ventricular subepicardial myocardium (i.e. in the outer layer of the heart muscle directly under the membrane enveloping the heart), which can successfully be treated with ablation.
It is also known that a significant proportion of patients with BrS and ERS, as well as some iVF survivors, harbor disease causing variants in SCN5A, the gene that encodes for the cardiac sodium channel, which is a major protein involved in electrical activity. However, the majority of genetic susceptibility of these disorders is likely to involve more genetic variation at the same time.
In this overview, we postulate that BrS, ERS, and iVF may form part of a spectrum of subtle subepicardial cardiomyopathy, i.e. diseases with slight structural changes in the outer layer of the heart muscle and not purely electrical diseases. We propose that impaired flow of sodium ions, along with genetic and environmental susceptibility, affects cardiac conduction particularly in the epicardium and that this leads to the characteristic changes on the ECG and the increased likelihood for potential fatal ventricular arrhythmias.
Translated by Arthur Wilde, Amsterdam UMC, Amsterdam, The Netherlands
Miles C, Boukens B, Scrocco C, Wilde AAM, Nademanee K, Haïssaguerre M, Coronel R, Behr ER. Subepicardial cardiomyopathy – a disease underlying J-wave syndromes and idiopathic ventricular fibrillation. Circulation 147, 1622-1633, 2023. PMID: 37216437