title: Torsades de pointes during complete atrioventricular block: Genetic factors and electrocardiogram correlates.
abstract: BACKGROUND
  Atrioventricular (AV) block is infrequently associated with QT prolongation and torsades de pointes (TdP). It was hypothesized that patients with AV block-mediated QT-related arrhythmia may have latent congenital long QT syndrome or a vulnerable genetic polymorphism.
  
  
  METHODS
  Eleven patients with complete AV block and TdP were prospectively identified. Patients underwent assessment, resting electrocardiography and telemetry at baseline, during AV block and pre-TdP. Genetic testing of KCNH2, KCNQ1, KCNE1, KCNE2 and SCN5A was performed. Thirty-three patients with AV block without TdP were included for comparison.
  
  
  RESULTS
  Genetic variants were identified in 36% of patients with AV block and TdP. Patients with AV block who developed TdP had significantly longer mean (+/- SD) corrected QT intervals (440+/-93 ms versus 376+/-40 ms, P=0.048) and Tpeak to Tend (Tp-Te) intervals (147+/-25 ms versus 94+/-25 ms, P=0.0001) than patients with AV block alone. In patients with a genetic variant, there was a significant increase in Tp-Te intervals at baseline, in AV block and pre-TdP compared with those who were genotype negative. A personal or family history of syncope or sudden death was more likely observed in patients with a genetic variant.
  
  
  CONCLUSIONS
  TdP in the setting of AV block may be a marker of an underlying genetic predisposition to reduced repolarization reserve. The Tp-Te interval at baseline, in AV block and pre-TdP may predict a genetic mutation or polymorphism compromising repolarization reserve. Patients with TdP in the setting of AV block represent a phenotypic manifestation of latent congenital long QT syndrome.
authors.affiliation: University of Western Ontario, London.
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Subbiah
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gollob
authors.forename: Lorne J
authors.initials: LJ
authors.lastname: Gula
authors.forename: Robert W
authors.initials: RW
authors.lastname: Davies
authors.forename: Peter
authors.initials: P
authors.lastname: Leong-Sit
authors.forename: Allan C
authors.initials: AC
authors.lastname: Skanes
authors.forename: Raymond
authors.initials: R
authors.lastname: Yee
authors.forename: George J
authors.initials: GJ
authors.lastname: Klein
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krahn
mesh_terms: D000368:Aged; D054537:Atrioventricular Block / Q000235:genetics* / Q000503:physiopathology*; D003645:Death, Sudden; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D015222:Sodium Channels / Q000235:genetics; D013575:Syncope / Q000235:genetics; D016171:Torsades de Pointes / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels
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