Published Online
on November 6, 2006

A more recent version of this article appeared on November 14, 2006

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Submitted on August 18, 2005
Revised on September 1, 2006
Accepted on September 8, 2006

Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome. Possible Therapy Implications

Hanno L. Tan MD, PhD, Abdennasser Bardai MSc, Wataru Shimizu MD, PhD, Arthur J. Moss MD, Eric Schulze-Bahr MD, Takashi Noda MD, and Arthur A.M. Wilde MD, PhD^*

From the Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (H.L.T., A.B., A.A.M.W.); Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Suita, Osaka, Japan (W.S., T.N.); Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (A.J.M.); and Department of Cardiology and Angiology and Leibniz Institute for Arteriosclerosis Research, University of Münster, Münster, Germany (E.S.-B.).

^* To whom correspondence should be addressed. E-mail: a.a.wilde{at}amc.uva.nl.

Background--The identification of the molecular-genetic substrate underlying the various forms of the congenital long-QT syndrome (LQTS) has sparked studies into possible genotype-phenotype correlations with the aim of developing genotype-tailored therapy. The onset of torsade de pointes (TdP) may differ among LQTS patients, being pause dependent in some but not all. This disparity may point to different arrhythmia mechanisms and may affect therapy strategies. We studied whether the proportion of pause-dependent TdP onset varies among LQTS genotypes.

Methods and Results--We studied all LQT1 (n=10), LQT2 (n=34), and LQT3 (n=6) patients from 4 centers for whom ECGs of TdP onset were available and analyzed whether pauses preceded TdP onset (first available ECG per patient). Pauses preceded TdP significantly more often in LQT2 (68%) than in LQT1 (0%), and the interval immediately before TdP (pause interval) was significantly longer in LQT2 than in LQT1. The proportion of pause dependence in LQT3 (33%) appeared intermediate, but this group was too small for statistical analysis.

Conclusions--Pause dependence of TdP onset is predominant in LQT2 but absent or rare in LQT1. It is suggested that disparities in pause dependence of TdP onset may reflect different arrhythmia mechanisms.

Key words: arrhythmia • electrophysiology • genetics • long-QT syndrome • torsade de pointes

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