title: Cardiac effects of chronic oral beta-blockade: lack of agreement between heart rate and QT interval changes.
abstract: BACKGROUND
  Although well established on the sinus node, the effects of beta-blockade on ventricular repolarization are still conflicting. The aim of the study was to investigate the effects of a chronic beta-blockade on sinus node and repolarization parameters and their relationship.
  
  
  METHODS
  Sixteen healthy volunteers (10 males, mean age: 40 +/- 6.7 years) were randomized to placebo or atenolol (100 mg). After 7 days, subjects were crossed over. Heart rate (HR) and HRV indices were calculated from long-term ECG recordings separately during the day and at night, together with ventricular repolarization parameters (QT interval duration and QT rate-dependence).
  
  
  RESULTS
  Mean R-R intervals were significantly and consistently increased after atenolol (Day: 916 +/- 103 ms vs. 712 +/- 89 ms, and Night: 1149 +/- 93 vs. 996 +/- 125 ms). HRV changes under atenolol were also consistent, with a significant decrease in sympathovagal ratio. In contrast, atenolol only lowered diurnal QT rate-dependence (0.123 +/- 0.032 vs. 0.190 +/- 0.065 on placebo, P < 0.001), but not the nocturnal pattern. After multivariate analysis QT rate-dependence changes induced by atenolol were correlated with pretreatment QT/RR relation (r = 0.65, P < 0.01) but not with any HR or HRV parameters.
  
  
  CONCLUSIONS
  In healthy subjects, repolarization changes following chronic beta-blockade cannot be predicted by HR or HRV changes, but are dependent on pretreatment rate-dependence.
authors.affiliation: Hôpital Lariboisière, Service de Cardiologie, 2 rue Ambroise Paré, 75010 Paris, France. fabrice.extramiana@lrb.ap-hop-paris.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Extramiana
authors.forename: Pierre
authors.initials: P
authors.lastname: Maison-Blanche
authors.forename: René
authors.initials: R
authors.lastname: Tavernier
authors.forename: Luc
authors.initials: L
authors.lastname: Jordaens
authors.forename: Antoine
authors.initials: A
authors.lastname: Leenhardt
authors.forename: Philippe
authors.initials: P
authors.lastname: Coumel
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001262:Atenolol / Q000494:pharmacology*; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol