title: High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment "failures".
abstract: BACKGROUND
  Beta-blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite beta-blocker therapy have not been ascertained.
  
  
  RESULTS
  This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with beta-blocker and followed up for a median time of 10 years. Before beta-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After beta-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before beta-blocker had CA/sudden death on beta-blockers.
  
  
  CONCLUSIONS
  beta-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. beta-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "beta-blocker failures." beta-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or beta-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.
authors.affiliation: Department of Medicine, LDS Hospital and University of Utah, Salt Lake City, UT, USA. g.michael.vincent@intermountainmail.org
authors.forename: G Michael
authors.initials: GM
authors.lastname: Vincent
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.forename: Heikki
authors.initials: H
authors.lastname: Swan
authors.forename: Candice
authors.initials: C
authors.lastname: Bithell
authors.forename: Carla
authors.initials: C
authors.lastname: Spazzolini
authors.forename: Lia
authors.initials: L
authors.lastname: Crotti
authors.forename: Kirsi
authors.initials: K
authors.lastname: Piippo
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lupoglazoff
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villain
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010349:Patient Compliance; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012189:Retrospective Studies; D029597:Romano-Ward Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations