Cardiac effects of chronic oral beta-blockade: lack of agreement between heart rate and QT interval changes.
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.
Extramiana
Fabrice
F
Hôpital Lariboisière, Service de Cardiologie, 2 rue Ambroise Paré, 75010 Paris, France. fabrice.extramiana@lrb.ap-hop-paris.fr
Maison-Blanche
Pierre
P
Tavernier
René
R
Jordaens
Luc
L
Leenhardt
Antoine
A
Coumel
Philippe
P
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
D000319:Adrenergic beta-Antagonists; D001262:Atenolol