CIRCADIAN AND POWER SPECTRAL CHANGES OF RR AND QT INTERVALS DURING TREATMENT OF PATIENTS WITH ANGINA-PECTORIS WITH NADOLOL PROVIDING EVIDENCE FOR DIFFERENTIAL AUTONOMIC MODULATION OF HEART-RATE AND VENTRICULAR REPOLARIZATION

This study evaluates the effects of autonomic manipulation by chronic beta blockade with nadolol on the circadian and power spectral changes of heart rate and QT interval. It was hypothesized that differential innervation of the atria and ventricles by sympathetic and parasympathetic fibers may produce differential effects an heart rate and QT interval variabilities. Halter recordings of 12 male patients (age 63 +/- 7 years) with stable angina were analyzed before and after 3 weeks of nadolol therapy. The QT intervals were individually normalized by an exponential for mula to study the circadian variation of QTc. Power spectra of RR and uncorrected QT intervals were obtained by fast-Fourier analysis from 256 consecutive sinus beats during the day at maximal heart rate and during the night at minimal heart rate. Frequency-specific variability was determined from areas under the spectral plots. Both heart rate and QTc exhibited significant circadian patterns (p < 0.01) in opposite phase with each other. Mean heart rate was significantly reduced with nadolol (81 +/- 12 vs 67 +/- 12 beats/min, p < 0.001), with greater reduction during daytime. The mean QTc was unexpectedly reduced after nadolol treatment, with borderline significance (p = 0.06). The RR variability in the frequency range of 0.05 to 0.25 Hz was significantly increased with nadolol at 3:00 A.M. (p < 0.01) but not at 1:00 P.M. The BT variability in the same frequency range was not significantly increased with nadolol. The power spectra of RR and QT intervals were dissimilar except at the lower frequencies around 0.05 Hz. Consistent with this observation, the QT versus RR plots of 256 beat-by-beat values showed poor correlation in all subjects. It is concluded that: (1) the RR power spectra from Holter recordings predominantly reflect vagal activity in the 0.05 to 0.25 Hz range; (2) the QT interval variability is rela tively insensitive to vagal activity; (3) QTc reduction with nadolol may reflect reduced dispersion of ventricular repolarization in the present patient group; and (4) the relation between RR and QT is frequency-dependent, and is effectively masked at frequencies > 0.05 Hz.