Published online before print October 4, 2004, doi: 10.1161/01.CIR.0000144471.98080.CA
(Circulation. 2004;110:2119-2124.)
© 2004 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
Spectrum and Frequency of Cardiac Channel Defects in Swimming-Triggered Arrhythmia Syndromes
From the Department of Pediatric and Adolescent Medicine/Division of Cardiovascular Disease (G.C., C.M.H., M.J.A.), the Department of Molecular Pharmacology and Experimental Therapeutics (L.J.K., D.J.T., M.L.W., C.M.H., M.J.A.), and the Department of Internal Medicine/Division of Cardiovascular Disease, Mayo Clinic College of Medicine (M.J.A.), Rochester, Minn.
Correspondence to Dr Michael J. Ackerman, Long QT Syndrome Clinic and the Sudden Death Genomics Laboratory, Guggenheim 501, 200 First St SW, Rochester, MN 55905. E-mail ackerman.michael{at}mayo.edu
Received April 23, 2004; revision received August 2, 2004; accepted August 4, 2004.
Background— Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events.
Methods and Results— Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2, was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a "Schwartz" score (
4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing RyR2 mutations.
Conclusions— In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.
Key Words: catecholamines • tachycardia • genes • ion channels • long-QT syndrome
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