Published Online
on October 4, 2004

A more recent version of this article appeared on October 12, 2004

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Submitted on April 23, 2004
Revised on August 2, 2004
Accepted on August 4, 2004

Spectrum and Frequency of Cardiac Channel Defects in Swimming-Triggered Arrhythmia Syndromes

Grace Choi MD, Laura J. Kopplin BS, David J. Tester BS, Melissa L. Will BS, Carla M. Haglund , and Michael J. Ackerman MD, PhD^*

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.

^* To whom correspondence should be addressed. E-mail: ackerman.michael{at}mayo.edu.

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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