Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study

• Published in: Circulation (New York, N.Y.) Vol. 134; no. 12; pp. 872 - 882
• Main Authors: Wilde, Arthur A.M, Moss, Arthur J, Kaufman, Elizabeth S, Shimizu, Wataru, Peterson, Derick R, Benhorin, Jesaia, Lopes, Coeli, Towbin, Jeffrey A, Spazzolini, Carla, Crotti, Lia, Zareba, Wojciech, Goldenberg, Ilan, Kanters, Jørgen K, Robinson, Jennifer L, Qi, Ming, Hofman, Nynke, Tester, David J, Bezzina, Connie R, Alders, Marielle, Aiba, Takeshi, Kamakura, Shiro, Miyamoto, Yoshihiro, Andrews, Mark L, McNitt, Scott, Polonsky, Bronislava, Schwartz, Peter J, Ackerman, Michael J
• Format: Journal Article
• Language: English
• Published: United States by the American College of Cardiology Foundation and the American Heart Association, Inc 20.09.2016
• Subjects: Adolescent; Adrenergic beta-Antagonists - therapeutic use; Adult; Cardiac Conduction System Disease; Child; Child, Preschool; Electrocardiography - methods; Female; Heart Arrest - drug therapy; Heart Arrest - etiology; Humans; Infant; Long QT Syndrome - diagnosis; Long QT Syndrome - drug therapy; Male; Registries; Risk Assessment; Sex Characteristics; Sodium Channels - genetics; Syncope - complications; Syncope - drug therapy; Young Adult; death, sudden, cardiac; risk assessment; SCN5A protein, human; arrhythmia, cardiac; genetic testing; long-QT syndrome
• DOI: 10.1161/CIRCULATIONAHA.116.021823
• ISSN: 0009-7322

BACKGROUND:Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population. METHODS:The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years. RESULTS:Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome–related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02). CONCLUSIONS:Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.