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.