title: Gene-specific effect of beta-adrenergic blockade on corrected QT interval in the long QT syndrome.
abstract: BACKGROUND
  In the long QT syndrome (LQTS) the effects of beta-blocker treatment on prevention of cardiac events differs according to the genotype. We aimed to assess the effect of beta-blocker treatment on QT/QTc duration in Type 1 LQTS (LQT1) and Type 2 LQTS (LQT2) patients.
  
  
  METHODS
  24-hour digital Holter ECG were recorded before and after beta-blocking therapy initiation in LQT1 (n = 30) and LQT2 patients (n = 16). QT duration was measured on consecutive 1-minute averaged QRS-T complexes leading to up to 1440 edited QT-RR pairs for each recording. We computed subject- and treatment-specific log/log QT/RR relationships which were used to correct the QT intervals. The QT duration was also evaluated at predefined heart rates and after correction using Bazett and Fridericia coefficients.
  
  
  RESULTS
  At baseline, individual QT/RR coefficients were higher in LQT2 than in LQT1 patients (0.53 ± 0.10 vs. 0.40 ± 0.11, P < 0.001) and QT1000 was longer in LQT2 than in LQT1 patients (521 ± 38 vs. 481 ± 39 ms, P < 0.01). Beta-blockers significantly prolonged the mean RR interval (from 827 ± 161 to 939 ± 197 ms, P < 0.0001). The individual QT/RR coefficients were not significantly modified by beta-blockers. Beta-blocker treatment was associated with a prolongation of the QT1000 interval (from 481 ± 39 to 498 ± 43 ms, P < 0.01) in LQT1 patients but with a shortening in LQT2 patients (from 521 ± 38 to 503 ± 32 ms, P < 0.01).
  
  
  CONCLUSIONS
  The effect of beta-adrenergic blockade on QTc duration is different in LQT1 and LQT2 patients. Our data suggest that, in LQT1 patients, the well-known positive effect of beta-blockade might be associated with a prolongation of QTc duration. The mechanisms of beta-blockade protection may be different in LQT1 and in LQT2 patients.
authors.affiliation: University Paris Diderot, Paris, France. fabrice.extramiana@bch.aphp.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Extramiana
authors.forename: Pierre
authors.initials: P
authors.lastname: Maison-Blanche
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.forename: Patrick
authors.initials: P
authors.lastname: De Jode
authors.forename: Anne
authors.initials: A
authors.lastname: Messali
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Labbé
authors.forename: Antoine
authors.initials: A
authors.lastname: Leenhardt
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000704:Analysis of Variance; D015331:Cohort Studies; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D015716:Electrocardiography, Ambulatory / Q000187:drug effects* / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D029597:Romano-Ward Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: QT duration; beta-blocker; long QT syndrome