Catecholaminergic polymorphic ventricular tachycardia: An exciting new era

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI) website. The first used the medical subject headings (MeSH) database using the term “catecholaminergic polymorphic ventricular tachycardia” that was run on the PubMed database using the age filter (birth to 18 years), and it yielded 58 results. The second search using the MeSH database with the search term “catecholaminergic polymorphic ventricular tachycardia,” applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.

The control of cardiac ventricular excitability by autonomic pathways

“…Arrhythmic events in patients with LQT1 and CPVT are now well established to be dependent on high sympathetic tone with exercise being a particular trigger (Schwartz et al, 2001;Behere and Weindling, 2016). In LQT1, this dependence on exercise/increased adrenergic tone for arrhythmogenesis relates to the previously described dependence on I Ks augmentation for APD shortening at high heart rates.…”

Gene Therapy for the Treatment of Cardiac Arrhythmias: Current and Emerging Applications

“…Catecholaminergic polymorphic VT (CPVT) is an inherited arrhythmia disorder in which exercise and emotional stress can cause life-threatening polymorphic VT. A common gene mutation in CPVT involves the membrane-binding protein calseqsterin (CASQ2), which is localized to the sarcoplasmic reticulum and is crucial to the proper calcium storage and regulation of APD. 46 In CPVT, this dysregulation in calcium handling causes delayed afterdepolarization as well as triggers activity due the diastolic release of calcium. To understand if gene transfer could improve calcium regulation, Denegri et al 47 developed a mouse model of CPVT by creating a knock-in mutation that disables CASQ2 gene expression.…”

Compound heterozygous CASQ2 mutations and long‐term course of catecholaminergic polymorphic ventricular tachycardia

“…Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, inherited cardiac disease that predisposes to malignant arrhythmias and sudden death (Behere and Weindling 2016). It is characterized by episodic polymorphic or bidirectional ventricular tachycardia in individuals with otherwise structurally normal hearts (Behere and Weindling 2016). Arrhythmias usually occur under conditions of beta-adrenergic stimulation, such as exercise or stress (Leenhardt et al 1995).…”