Calcium polymorphic ventricular tachycardia: a new name for CPVT?

Abstract

This editorial refers to ‘Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse ardiomyocytes with a human CPVT mutation’ by S. Sedej et al ., pp. 50–59, this issue. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated ventricular tachyarrhythmia leading to syncope and sudden cardiac death.1 Patients with CPVT show ventricular tachycardia during exercise or emotional stress in the absence of any structural heart disease. Also, any increase in the levels of circulating catecholamines (during stress or exercise, i.e. β-adrenergic stimulation) leads to a bi-directional ventricular tachycardia. Since 2001, more than 70 mutations in either ryanodine receptors (RyR) or an RyR-associated protein [calsequestrin, involved in sarcoplasmic reticulum (SR) Ca2+ buffering] have been identified in CPVT families.2,3 During the last several years, the physiological consequences of such mutations have been mainly investigated in expression systems (e.g. HEK cells expressing mutant RyR).4,5 However, expression systems lack a cardiac intracellular environment (accessory proteins, cell structure, etc.), hampering a complete understanding of how such mutations induce cardiac arrhythmias in native cardiac myocytes. The development of the first knock-in mouse model of human CPVT (mutation in RyR at position R4496C) by Priori's group2 shows that the mouse phenotype has striking similarity with the clinical human CPVT symptoms. Since then, it has been possible to investigate the effect of …