Time-series analysis of long-term ambulatory myocardial ischemia: Effects of β-adrenergic and calcium channel blockade

We have previously demonstrated the utility of time-series analysis applied to 72-hour ambulatory electrocardiographic data in patients with coronary artery disease. The present investigation applied time-series analysis to long-term (120-hour) ambulatory electrocardiographic data to determine the minimal period of monitoring needed (1) to detect periodicity of ischemia-related variables in ambulatory patients, (2) to describe auto-correlation and cross-correlation functions for heart rate and ischemia, and (3) to describe the effects of β-adrenergic and calcium channel blockade on circadian characteristics and coupling of heart rate and ischemia. A double-blind crossover design was used to obtain 120-hour recordings during placebo, atenolol (200 mg/day), and diltiazem (360 mg/day) administration. During all three treatment periods, distinct circadian variation of heart rate was documented by autocorrelation and Fourier analysis. Ischemia did not exhibit clear periodicity as indexed by autocorrelation in any period; however, it was coupled to heart rate in all treatment periods as reflected in cross-correlation analysis. Although diltiazem did not quantitatively alter the circadian characteristics of heart rate or ischemia, atenolol produced a shift in the coupling between remaining ischemia and heart rate in time. Significant autocorrelation was detected for all treatment periods after 72 hours of monitoring, suggesting that 72 hours is the minimum amount of time needed for analysis of ambulatory electrocardiographic data in patients with coronary artery disease.