Long-term variation in myocardial ischemia during daily life in patients with stable coronary artery disease: Its relation to changes in the ischemic threshold

Long-term variation in the frequency of myocardial ischemia during daily activity in patients with coronary artery disease who do not experience symptomatic changes has not been documented. Because at one point in time, the magnitude of such ischemia is strongly related to the ischemic threshold measured during exercise testing, this study was undertaken to determine whether patients with stable coronary artery disease show long-term variations in the frequency and duration of myocardial ischemia and to establish whether such variability is related to parallel changes in the ischemic threshold during exercise testing. Forty consecutive patients (mean age 61 ± 8 years) who showed a stable clinical course over ≥12 months were studied with a repeat exercise treadmill test and ambulatory electrocardiographic (ECG) monitoring after withdrawal of antianginal medications. The ischemic threshold was determined as the exercise time at 1 mm of ST segment depression. The mean interval to both follow-up evaluations was 15 ± 3 months. Among the 23 patients with myocardial ischemia on ambulatory ECG monitoring at initial evaluation, the number and duration of ischemic episodes at follow-up were increased in 5 patients (mean increase 3.6 ± 2 episodes and 123 ± 98 min), unchanged in 1 patient and decreased in 17 patients (mean decrease 2.6 ± 2 episodes and 98 ± 72 min). Of the 17 patients without ischemic episodes at initial evaluation, 3 had evidence of ischemia on follow-up ambulatory ECG monitoring. During follow-up exercise testing, the exercise ischemic threshold decreased significantly (from 12.5 ± 6 to 8 ± 4 min; p < 0.001) in those patients in whom the frequency (and duration) of myocardial ischemia on ambulatory monitoring increased. Conversely, the ischemic threshold significantly increased (from 8 ± 5 to 10.2 ± 5 min; p < 0.001) in those patients in whom the number (and duration) of ischemic episodes decreased during follow-up. The variations in the frequency of myocardial ischemia during follow-up ambulatory monitoring significantly correlated with the changes in exercise ischemic threshold (r = −0.62; p < 0.0001). These findings indicate that patients with coronary artery disease may show long-term variations in myocardial ischemia during daily activity, even without simultaneous symptomatic changes. The occurrence and magnitude of this variation are closely related to parallel changes in the exercise ischemic threshold. These findings may have important implications for the understanding of the mechanisms and prevalence of ischemia during daily activity and the longitudinal evaluation of patients with stable coronary artery disease.