Published Online
on April 21, 2008

A more recent version of this article appeared on April 29, 2008

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Submitted on July 22, 2007
Accepted on January 29, 2008

Long-QT Syndrome After Age 40

Ilan Goldenberg MD^*, Arthur J. Moss MD, James Bradley MS, Slava Polonsky MS, Derick R. Peterson PhD, Scott McNitt MS, Wojciech Zareba MD, PhD, Mark L. Andrews BBA, Jennifer L. Robinson MS, Michael J. Ackerman MD, PhD, Jesaia Benhorin MD, Elizabeth S. Kaufman MD, Emanuela H. Locati MD, Carlo Napolitano MD, Silvia G. Priori MD, PhD, Ming Qi MD, Peter J. Schwartz MD, Jeffrey A. Towbin MD, G. Michael Vincent MD, and Li Zhang MD

From the Cardiology Division of the Department of Medicine (I.G., A.J.M., J.B., S.P., S.M., W.Z., M.L.A., J.L.R.), Biostatistics and Computational Biology (D.R.P.), and Pathology (M.Q.), University of Rochester Medical Center, Rochester, NY; Departments of Medicine, Pediatrics, and Molecular Pharmacology (M.J.A.), Mayo Clinic College of Medicine, Rochester, Minn; Cardiovascular Department De Gasperis (E.H.L.), Niguarda Hospital, Milan, Italy; Bikur Cholim Hospital (J.B.), University of Jerusalem, Jerusalem, Israel; The Heart and Vascular Research Center (E.S.K.), MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio; Molecular Cardiology (C.N., S.G.P.), Fondazione S. Maugeri–University of Pavia and the Department of Cardiology (P.J.S.), Fondazione Policlinico S. Matteo IRCCS and University of Pavia, Pavia, Italy; Department of Pediatric Cardiology (J.A.T.), Baylor College of Medicine, Houston, Tex; and Department of Medicine (G.M.V., L.Z.), University of Utah School of Medicine, Salt Lake City, Utah.

^* To whom correspondence should be addressed. E-mail: Ilan.Goldenberg{at}heart.rochester.edu.

Background—Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied.

Methods and Results—The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] 470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc <440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.65 (P<0.001) in the age range of 41 to 60 years and 1.23 (P=0.31) in the age range of 61 to 75 years. The clinical course of study subjects displayed gender differences: Affected LQTS women experienced a significantly higher cumulative event rate (26%) than borderline (16%) and unaffected (12%) women (P=0.001), whereas event rates were similar among the 3 respective subgroups of men (29%, 26%, and 27%; P=0.16). Recent syncope (<2 years in the past) was the predominant risk factor in affected subjects (hazard ratio 9.92, P<0.001), and the LQT3 genotype was identified as the most powerful predictor of outcome in a subset of 871 study subjects who were genetically tested for a known LQTS mutation (hazard ratio 4.76, P=0.02).

Conclusions—LQTS subjects maintain a high risk for life-threatening cardiac events after age 40 years. The phenotypic expression of affected subjects is influenced by age-specific factors related to gender, clinical history, and the LQTS genotype.

Key words: long-QT syndrome • risk factors • mortality

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