OBJECTIVES: This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. BACKGROUND: Current data regarding the outcome of patients with concealed LQTS are limited. METHODS: Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤ 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤ 440 ms [n = 1,525]). RESULTS: The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age > 13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). CONCLUSIONS: Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
OBJECTIVES: This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. BACKGROUND: Current data regarding the outcome of patients with concealed LQTS are limited. METHODS: Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤ 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤ 440 ms [n = 1,525]). RESULTS: The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age > 13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). CONCLUSIONS: Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
Authors: Wojciech Zareba; Arthur J Moss; Emanuela H Locati; Michael H Lehmann; Derick R Peterson; W Jackson Hall; Peter J Schwartz; G Michael Vincent; Silvia G Priori; Jesaia Benhorin; Jeffrey A Towbin; Jennifer L Robinson; Mark L Andrews; Carlo Napolitano; Katherine Timothy; Li Zhang; Aharon Medina Journal: J Am Coll Cardiol Date: 2003-07-02 Impact factor: 24.094
Authors: A J Moss; P J Schwartz; R S Crampton; D Tzivoni; E H Locati; J MacCluer; W J Hall; L Weitkamp; G M Vincent; A Garson Journal: Circulation Date: 1991-09 Impact factor: 29.690
Authors: Wataru Shimizu; Arthur J Moss; Arthur A M Wilde; Jeffrey A Towbin; Michael J Ackerman; Craig T January; David J Tester; Wojciech Zareba; Jennifer L Robinson; Ming Qi; G Michael Vincent; Elizabeth S Kaufman; Nynke Hofman; Takashi Noda; Shiro Kamakura; Yoshihiro Miyamoto; Samit Shah; Vinit Amin; Ilan Goldenberg; Mark L Andrews; Scott McNitt Journal: J Am Coll Cardiol Date: 2009-11-24 Impact factor: 24.094
Authors: W Zareba; A J Moss; P J Schwartz; G M Vincent; J L Robinson; S G Priori; J Benhorin; E H Locati; J A Towbin; M T Keating; M H Lehmann; W J Hall Journal: N Engl J Med Date: 1998-10-01 Impact factor: 91.245
Authors: Alon Barsheshet; Arthur J Moss; Scott McNitt; Slava Polonsky; Coeli M Lopes; Wojciech Zareba; Jennifer L Robinson; Michael J Ackerman; Jesaia Benhorin; Elizabeth S Kaufman; Jeffrey A Towbin; G Michael Vincent; Ming Qi; Ilan Goldenberg Journal: Circ Cardiovasc Genet Date: 2011-08-10
Authors: Leigh Anne Swayne; Nathaniel P Murphy; Sirisha Asuri; Lena Chen; Xiaoxue Xu; Sarah McIntosh; Chao Wang; Peter J Lancione; Jason D Roberts; Charles Kerr; Shubhayan Sanatani; Elizabeth Sherwin; Crystal F Kline; Mingjie Zhang; Peter J Mohler; Laura T Arbour Journal: Circ Cardiovasc Genet Date: 2017-01