Ventricular arrhythmogenesis in pulmonary hypertension: From right ventricular remodeling to clinical implications.

Pulmonary hypertension (PH) results in chronic pressure overload of the right ventricle, leading to progressive structural, metabolic, neurohumoral, and electrophysiological remodeling. Although right ventricular failure is the major determinant of outcomes in PH, these remodeling processes may also create a substrate for ventricular arrhythmogenesis, thereby contributing to poor outcomes. While atrial arrhythmias are more common, ventricular arrhythmias (VAs) have also been reported in PH and may have important clinical implications. However, their epidemiology, mechanisms, and optimal management remain incompletely understood. This review summarizes pathophysiological mechanisms of VAs in PH by integrating findings from preclinical and clinical investigations. Available data show that premature ventricular contractions and non-sustained ventricular tachycardia are the most frequently reported VAs, whereas sustained ventricular tachycardia and ventricular fibrillation appear to be uncommon. Arrhythmia susceptibility in PH is associated with several mechanisms that provide possible therapeutic targets. These include changes in specific ion channels in the right ventricle, abnormalities in calcium handling, structural remodeling characterized by hypertrophy, fibrosis and gap junction alterations, autonomic nervous system imbalance, myocardial ischemia, inflammation, and oxidative stress. We discuss the translational implications of these findings and highlight gaps in knowledge to guide future research on the epidemiology, targeted management, and prognostic significance of VAs in PH.