title: Torsades de pointes following acute myocardial infarction: evidence for a deadly link with a common genetic variant.
abstract: BACKGROUND
  Although QT prolongation following myocardial infarction (MI) is generally moderate, cases with marked QT prolongation leading to life-threatening torsades de pointes (TdP) have been described.
  
  
  OBJECTIVE
  To investigate the genetic substrate of this phenomenon.
  
  
  METHODS
  We studied 13 patients who developed TdP in the subacute phase of MI (2-11 days) and a group of 133 ethnically matched controls with uncomplicated MI. Long QT syndrome genes and the KCNH2-K897T polymorphism were screened by using denaturing high-performance liquid chromatography plus direct sequencing and a specific TaqMan assay, respectively.
  
  
  RESULTS
  Two of the 13 patients (15%) who presented with QT prolongation and TdP were found to carry long QT syndrome mutations (KCNH2-R744X and SCN5A-E446K). Nine of the remaining 11 patients (82%) carried the KCNH2-K897T polymorphism, which was present in 35% of the controls (P = .0035). Thus, patients with an acute MI carrying the KCNH2-K897T polymorphism had an 8-fold greater risk of experiencing TdP compared with controls (95% confidence interval = 2-40).
  
  
  CONCLUSIONS
  Our data suggest that the common K897T polymorphism is associated with an increased risk of TdP developing in the subacute phase of MI. Our findings support the concept that the electrical remodeling associated with this healing phase of MI may unmask a genetic substrate predisposing to a time-limited development of life-threatening arrhythmias. They also provide the first line of evidence in support of the hypothesis that a common polymorphism, previously described as a modifier of the severity of LQTS, may increase the risk of life-threatening arrhythmias in a much more prevalent cardiac disease such as myocardial infarction.
authors.affiliation: Section of Cardiology, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Crotti
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Hector
authors.initials: H
authors.lastname: Barajas-Martinez
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliva
authors.forename: Roberto
authors.initials: R
authors.lastname: Insolia
authors.forename: Guido D
authors.initials: GD
authors.lastname: Pollevick
authors.forename: Federica
authors.initials: F
authors.lastname: Dagradi
authors.forename: Alejandra
authors.initials: A
authors.lastname: Guerchicoff
authors.forename: Federica
authors.initials: F
authors.lastname: Greco
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Sami
authors.initials: S
authors.lastname: Viskin
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D016757:Death, Sudden, Cardiac; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016171:Torsades de Pointes / Q000209:etiology* / Q000235:genetics*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human