Catecholaminergic polymorphic ventricular tachycardia: A paradigm to understand mechanisms of arrhythmias associated to impaired Ca2+ regulation

Cardiovascular Genetics, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, USA.
Heart rhythm: the official journal of the Heart Rhythm Society (Impact Factor: 5.08). 11/2009; 6(11):1652-9. DOI: 10.1016/j.hrthm.2009.06.033
Source: PubMed


In the 8 years since the discovery of the genetic bases of catecholaminergic polymorphic ventricular tachycardia (CPVT), we have witnessed a remarkable improvement of knowledge on arrhythmogenic mechanisms involving disruption of cardiac Ca(2+) homeostasis. Studies on the consequences of RyR2 and CASQ2 mutations in cellular systems and mouse models have shed new light on pathways that are also implicated in arrhythmias occurring in highly prevalent diseases, such as heart failure. This research track has also led to the identification of therapeutic targets of potential clinical impact to abate the burden of sudden death in CPVT. Here, we review the current knowledge on the pathophysiology of CPVT also highlighting the existing controversies and possible future development.

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    • "Up to 50 % of mortality in heart failure does not result from pump failure but from ventricular tachyarrhythmias (Grimm and Maisch 2002) that are the consequence of dysfunctions in cardiac Ca2+ homeostasis: Resting (diastolic) Ca2+ which is increased in heart failure(Gwathmey et al. 1990) as well as SR Ca2+ leak in a rare genetic disease called CPVT (Lehnart et al. 2008) can result in transient inward currents mediated by the sarcolemmal Na+/Ca2+ exchanger that, in turn, can lead to DADs and triggered activity. Both HF and CPVT have been linked to aberrant Ca2+ release through ‘leaky’ RyR2 channels (see Lehnart et al. 2009; Cerrone et al. 2009; Kushnir and Marks 2010 for recent reviews). "
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