Consequences of Right Heart Disease for Cardiac Electrophysiology and Arrhythmias: Cellular and Structural Mechanisms

Conditions provoking the electrical and structural-functional remodelling of the myocardium can lead to the development of heart rhythm disorders, including atrial fibrillation (AF) and ventricular tachyarrhythmias that can cause sudden cardiac death. Right heart disease (RHD) causes progressive structural and functional remodelling of the right heart responsible for right ventricular and atrial dysfunction and arrhyhmias. Conditions contributing to the development of RHD include left heart disease, pulmonary arterial hypertension, congenital heart disease, right-sided myocardial infarction due to coronary artery occlusion, and amyloidosis. In adult patients with RHD associated with pulmonary arterial hypertension, the prevalence of AF is about 20%, and in adult patients with arrhythmogenic right ventricular cardiomyopathy, it is 14%. A study has suggested that compared to non patients without congenital heart disease, AF appears 30 years earlier in adult patients with congenital heart disease, with a 10-20-fold-higher incidence. This narrative review article aims to review knowledge about the pathophysiology of RHD associated with cardiac arrhythmia. Evidence is reported about the mechanisms underlying the initiation and maintenance of the arrhythmogenic substrate in RHD. We summarize the available experimental approaches to study RHD associated with cardiac arrhythmia, including in vitro models (isolated cardiomyocytes, fibroblasts) and in vivo models (monocrotaline, pulmonary artery banding, Sugen/hypoxia). In addition, we discuss potential future strategies targeting myocardial inflammation and fibrosis in the prevention of cardiac arrhythmia in RHD.