Catecholaminergic Polymorphic Ventricular Tachycardia in 2012

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, potentially lethal inherited arrhythmia syndrome characterized by stress or emotion-induced ventricular arrhythmias. CPVT was first described in 1960, while the genetic basis underlying this syndrome was discovered in 2001. The past decade has seen substantial advances in understanding the pathophysiology of CPVT. In addition, significant advances have been made in elucidating clinical characteristics of CPVT patients and new treatment options have become available. Here, we review current literature on CPVT to present state-of-the-art knowledge on the subject of the genetic basis, pathophysiology, clinical presentation, diagnosis, treatment and prognosis.

Conduction Slowing Contributes to Spontaneous Ventricular Arrhythmias in Intrinsically Active Murine RyR2‐P2328S Hearts

“…It is associated with genetic abnormalities in the cardiac ryanodine receptor (RyR2) 1,3 and the calsequestrin ( CASQ2) 2 gene. Detailed mechanisms underlying sustained arrhythmias, however, are incompletely understood, and pharmacological treatments remain only partially effective 4,5 . Features of CPVT have been replicated by several mouse models and expression systems variously containing C‐terminal RyR2‐R4496C , 6 N‐terminal RyR2‐R176Q , 7 and central domain RyR2‐R2474S , 8 RyR2‐P2328S , 9 and RyR2‐S2246L 10 mutations.…”

Ion Channels and Beating Heart: The Players and the Music

“…The clinical diagnosis is often possible with an exercise stress test, revealing typical ventricular rhythm abnormalities. 11 Clinical heterogeneity and incomplete penetrance are other well-recognized features of channelopathies and research is underway to identify these modifying genetic traits (i.e. SNPs) and epigenetic mechanisms (i.e.…”

“…In LQTS for instance, the molecular screening is positive in 80% of affected patients and may be helpful for sudden death risk evaluation and for the correct management of the patients; 7 in CPVT the yield of genetic test is high as well (70%), however, despite being useful for diagnosis, it is not useful for making therapeutic decisions. 11 In the case of SQTS, the known disease-associated genes has been shown to account for approximately 30% of probands (unpublished observation); molecular screening is of value in choosing a therapeutic approach, since traditional I Kr blockers, including sotalol and dofetilide are ineffective in many cases of SQT1 because they depend on the inactivated state of the HERG channel (which is lost) in order to exert their inhibitory effect. Quinidine, on the other hand, because it interacts with the activated state of the I Kr channel, is effective in reducing the augmented I Kr responsible for the disease.…”