This Article Full Text Full Text (PDF) All Versions of this Article: 114/20/2096    most recent CIRCULATIONAHA.106.642694v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tan, H. L. Articles by Wilde, A. A. M. Search for Related Content PubMed PubMed Citation Articles by Tan, H. L. Articles by Wilde, A. A. M. Related Collections Clinical genetics Arrhythmias, clinical electrophysiology, drugs Electrocardiology Genetics of cardiovascular disease Related Article

(Circulation. 2006;114:2096-2103.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

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; 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.).

Correspondence to Arthur A.M. Wilde, MD, PhD, Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail a.a.wilde{at}amc.uva.nl

Received August 18, 2005; de novo received May 29, 2006; revision received September 1, 2006; accepted September 8, 2006.

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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2006 114: 2089. [Full Text]

This article has been cited by other articles:

				C. I. Berul Congenital Long-QT Syndromes: Who's at Risk for Sudden Cardiac Death? Circulation, April 29, 2008; 117(17): 2178 - 2180. [Full Text] [PDF]

				D. M. Roden Long-QT Syndrome N. Engl. J. Med., January 10, 2008; 358(2): 169 - 176. [Full Text] [PDF]

				I. C. Van Gelder, on behalf of the EHRA Education Committee, G. Boriani, S. Ernst, H. Heidbuchel, A. Zaza, M. Makijarvi, B. Gorenek, and C. B. Lundquist Case of polymorphic ventricular tachycardia after stroke necessitating defibrillation Europace, January 1, 2008; 10(1): 124 - 125. [Full Text] [PDF]

				L. Fabritz Drug-induced torsades de pointes -- A form of mechano-electric feedback? Cardiovasc Res, November 1, 2007; 76(2): 202 - 203. [Full Text] [PDF]

				D. J. Gallacher, A. Van de Water, H. van der Linde, A. N. Hermans, H. R. Lu, R. Towart, and P. G.A. Volders In vivo mechanisms precipitating torsades de pointes in a canine model of drug-induced long-QT1 syndrome Cardiovasc Res, November 1, 2007; 76(2): 247 - 256. [Abstract] [Full Text] [PDF]

				R. Passman and A. Kadish Sudden Death Prevention With Implantable Devices Circulation, July 31, 2007; 116(5): 561 - 571. [Full Text] [PDF]