title: Genotype-specific onset of arrhythmias in congenital long-QT syndrome: possible therapy implications.
abstract: BACKGROUND
  The identification of the molecular-genetic substrate underlying the various forms of the congenital long-QT syndrome (LQTS) has sparked studies into possible genotype-phenotype correlations with the aim of developing genotype-tailored therapy. The onset of torsade de pointes (TdP) may differ among LQTS patients, being pause dependent in some but not all. This disparity may point to different arrhythmia mechanisms and may affect therapy strategies. We studied whether the proportion of pause-dependent TdP onset varies among LQTS genotypes.
  
  
  RESULTS
  We studied all LQT1 (n=10), LQT2 (n=34), and LQT3 (n=6) patients from 4 centers for whom ECGs of TdP onset were available and analyzed whether pauses preceded TdP onset (first available ECG per patient). Pauses preceded TdP significantly more often in LQT2 (68%) than in LQT1 (0%), and the interval immediately before TdP (pause interval) was significantly longer in LQT2 than in LQT1. The proportion of pause dependence in LQT3 (33%) appeared intermediate, but this group was too small for statistical analysis.
  
  
  CONCLUSIONS
  Pause dependence of TdP onset is predominant in LQT2 but absent or rare in LQT1. It is suggested that disparities in pause dependence of TdP onset may reflect different arrhythmia mechanisms.
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.a.wilde@amc.uva.nl
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
authors.forename: Abdennasser
authors.initials: A
authors.lastname: Bardai
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: Takashi
authors.initials: T
authors.lastname: Noda
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D015203:Reproducibility of Results; D012737:Sex Factors; D016171:Torsades de Pointes / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000319:Adrenergic beta-Antagonists