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(Circulation. 2000;102:2796.)
© 2000 American Heart Association, Inc.

Editorials

Predicting the Long-QT Genotype From Clinical Data

From Sense to Science

Arthur A. M. Wilde, MD; Dan M. Roden, MD

From the Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, and the Interuniversity Cardiology Institute, Netherlands (A.A.M.W.), and the Division of Clinical Pharmacology and Arrhythmia Service, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn (D.M.R.).

Correspondence to Dr A.A.M. Wilde, Academic Medical Center, University of Amsterdam, Department of Clinical and Experimental Cardiology, M-0-052, PO Box 22700, 1100 DE Amsterdam, Netherlands. E-mail a.a.wilde@amc.uva.nl

Key Words: Editorials • long-QT syndrome • genes • arrhythmias

In the past 3 decades, the congenital long-QT syndrome (LQTS) has emerged as an important paradigm for understanding arrhythmogenesis. An understanding of the electrophysiological basis of arrhythmias in LQTS has now merged with new molecular genetics, solving some problems and raising new ones both in clinical management and in basic arrhythmia mechanisms (for review, see Roden and Spooner¹ ). In this scientific evolution, the international LQT registry has proved to be of paramount importance. Since 1979, data from this registry have proved to be of great value for the diagnosis, prognosis, and management of LQT patients and their relatives, and in more recent years, data from the registry represent a reliable source for attempts to correlate phenotype with genotype and vice versa.

Variability in Presentation of LQTS

We now understand that LQTS can arise as a result of mutations in multiple genes, each encoding an ion channel structural unit. Because ion channels have different time and voltage characteristics, it is tempting to speculate that the clinical presentation may be gene specific, and indeed emerging data support this idea (Table). Phenotypical differences in genetically distinct forms of LQTS may include every aspect of the clinical presentation, ie, the ECG appearance of the ST-T–wave patterns and arrhythmias, symptoms that trigger arrhythmias, QT dynamics during exercise or other triggers, efficacy of different treatment modalities, and the clinical course of affected patients (Table).

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics in Common Forms of LQTS

A gene-differentiating potential has indeed been shown for symptom-related triggers: swimming and acoustic stimuli typically trigger events . . . [Full Text of this Article]

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