title: Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals.
abstract: OBJECTIVE
  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.affiliation: Cardiology Division of Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA. ilan.goldenberg@heart.rochester.edu
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Samuel
authors.initials: S
authors.lastname: Horr
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Coeli M
authors.initials: CM
authors.lastname: Lopes
authors.forename: Alon
authors.initials: A
authors.lastname: Barsheshet
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Mark L
authors.initials: ML
authors.lastname: Andrews
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Emanuela H
authors.initials: EH
authors.lastname: Locati
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Jesaia
authors.initials: J
authors.lastname: Benhorin
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Kaufman
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Pyotr G
authors.initials: PG
authors.lastname: Platonov
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: G Michael
authors.initials: GM
authors.lastname: Vincent
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D014943:Global Health; D006323:Heart Arrest / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult