title: Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers.
abstract: BACKGROUND
  Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.
  
  
  OBJECTIVE
  To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients.
  
  
  METHODS
  Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years.
  
  
  METHODS
  Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype.
  
  
  RESULTS
  Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).
  
  
  CONCLUSIONS
  Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.
authors.affiliation: Molecular Cardiology, IRCCS Fondazione Maugeri, University of Pavia, Pavia, Italy. spriori@fsm.it
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Grillo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.forename: Elena
authors.initials: E
authors.lastname: Ronchetti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Moncalvo
authors.forename: Chiara
authors.initials: C
authors.lastname: Tulipani
authors.forename: Alessia
authors.initials: A
authors.lastname: Veia
authors.forename: Georgia
authors.initials: G
authors.lastname: Bottelli
authors.forename: Janni
authors.initials: J
authors.lastname: Nastoli
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D018450:Disease Progression; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005838:Genotype; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels