title: Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations.
abstract: BACKGROUND
  Patients with long QT syndrome (LQTS) who harbor multiple mutations (i.e. ≥ 2 mutations in ≥ 1 LQTS-susceptibility gene) may experience increased risk for life-threatening cardiac events.
  
  
  OBJECTIVE
  The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a single mutation.
  
  
  METHODS
  The risk for life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. single mutations, was assessed among 403 patients from the LQTS Registry.
  
  
  RESULTS
  Patients with multiple mutations (n=57) exhibited a longer QTc at enrollment compared with those with a single mutation (mean ± SD: 506 ± 72 vs. 480 ± 56 msec, respectively; P=0.003) and had a higher rate of life threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac events as compared to patients with a single mutation. The presence of multiple mutations in a single LQTS gene was associated with a 3.2-fold increased risk for life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving >1 LQTS gene was not significantly different from the risk associated with a single mutation (HR 1.7, P=0.26).
  
  
  CONCLUSIONS
  LQTS patients with multiple mutations have a greater risk for life-threatening cardiac events as compared to patients with a single mutation.
authors.affiliation: Cardiology Division, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Mullally
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Coeli M
authors.initials: CM
authors.lastname: Lopes
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Jesaia
authors.initials: J
authors.lastname: Benhorin
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Kaufman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Alon
authors.initials: A
authors.lastname: Barsheshet
mesh_terms: D000328:Adult; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014943:Global Health; D006801:Humans; D015994:Incidence; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D009154:Mutation; D012042:Registries; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D055815:Young Adult