Long-QT Syndrome After Age 40

Author:

Goldenberg Ilan1,Moss Arthur J.1,Bradley James1,Polonsky Slava1,Peterson Derick R.1,McNitt Scott1,Zareba Wojciech1,Andrews Mark L.1,Robinson Jennifer L.1,Ackerman Michael J.1,Benhorin Jesaia1,Kaufman Elizabeth S.1,Locati Emanuela H.1,Napolitano Carlo1,Priori Silvia G.1,Qi Ming1,Schwartz Peter J.1,Towbin Jeffrey A.1,Vincent G. Michael1,Zhang Li1

Affiliation:

1. 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,...

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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