Catecholaminergic Polymorphic Ventricular Tachycardia from Bedside to Bench and Beyond
Section snippets
Clinical Manifestations
As previously stated, the first comprehensive description of CPVT was provided in 1995 by Leenhardt et al,5 who described 21 patients (12 males), 20 of whom had suffered from syncopal episode(s). Almost half of the patients had been diagnosed as suffering from epilepsy prior to being correctly diagnosed with CPVT. Their age at first syncope ranged between 3 and 16 years (mean, 7.8 ± 4) and they had a slow resting heart rate of 60 ± 9 bpm. Physical examination, baseline electrocardiograms, and
Sinus Bradycardia in CPVT
Sinus bradycardia was reported by Leenhardt et al in 19955 but was not mentioned by Priori et al.11 This feature was later described in 29 nongenotyped Japanese CPVT patients14 and in a European series of 12 families carrying 13 different RyR2 missense mutations.12 Mutation carriers in these series had a resting heart rate that was 20 beats/min lower than that of age- and gender-matched controls, and 12 beats/min lower than that of their nonaffected family members. The heart rate of affected
CPVT and Congenital LQTS
It is obvious that phenotypical CPVT is quite similar to congenital LQTS.16 In fact, 9 of the 30 probands in the Priori series11 were misdiagnosed as “LQTS with normal QT interval”16 because syncope occurred during emotion and exercise. Tester et al17 found RyR2 mutations in 17 of 269 (6%) unrelated, genotype-negative patients referred for LQTS genetic testing. Interestingly, the presentation was near-drowning in five and excitement- or exertion-related syncope in three patients. Six patients
Molecular Basis of Calcium-Mediated Arrhythmia
The following sections review the physiology of excitation-contraction coupling, providing the background for discussing the pathogenesis of calcium-mediated arrhythmia in general and genetically determined CPVT in particular.
Acknowledgments
We appreciate the help of Dr. Steve de Palma from Harvard University, Boston and Daniela Tchetchik from Tel Aviv University in preparing the illustrations. Elaine Finkelstein and Vivienne York provided invaluable assistance in editing this manuscript. This project is supported by a grant from the Israel Science Foundation.
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