Abstract
His-Purkinje-related ventricular arrhythmias are a subset of ventricular tachycardias that use the specialized cardiac conduction system. These arrhythmias can occur in various different forms of structural heart disease. Here, we review the basic science discoveries and their analogous clinical observations that implicate the His-Purkinje system as a crucial component of the arrhythmia circuit. While mutations serve the molecular basis for arrhythmias in the heritable cardiomyopathies, transcriptional and posttranslational changes constitute the adverse remodeling leading to arrhythmias in acquired structural heart disease. Additional studies on the electrical properties of the His-Purkinje network and its interactions with the surrounding myocardium will improve the clinical diagnosis and treatment of these arrhythmias.