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Variability of transient myocardial ischemia in ambulatory patients with coronary artery disease
E G Nabel1, J Barry, M B Rocco
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Insights
Variability in ambulatory electrocardiographic (ECG) monitoring for chronic stable angina impacts clinical trial design. Understanding ST segment depression variations is crucial for detecting therapeutic effects in patients with coronary artery disease.
Area of Science:
- Cardiology
- Medical Technology
- Clinical Research
Background:
- Ambulatory electrocardiographic (ECG) monitoring reveals frequent ischemic ST segment depression in chronic stable angina.
- Clinical application necessitates understanding the variability in these ischemic episodes.
Purpose of the Study:
- To evaluate variations in the frequency and duration of ST segment depression episodes.
- To inform clinical trial design by quantifying temporal variability in ambulatory ECG data.
Main Methods:
- Analyzed ambulatory ECG recordings from 42 patients with chronic stable angina over daily, weekly, and monthly intervals.
- Utilized a nested analysis of variance to estimate variance components.
- Derived power calculations and minimum significant percent reductions for ischemia frequency and duration.
Main Results:
- Detected 1,262 episodes of ischemic ST segment depression over 4,656 monitoring hours.
- Mean episode frequency was 6.3/24 hr and mean duration was 18.3/24 hr.
- Significant changes in ischemia detection depend on sample size, monitoring duration, and intervals between sessions.
Conclusions:
- Temporal variability significantly influences the ability to detect therapeutic interventions in chronic stable angina.
- Clinical trials require careful consideration of monitoring parameters to distinguish true treatment effects from spontaneous variations.
- Eliminating ischemic episodes may be necessary for single-patient monitoring to detect significant therapeutic changes.
Abstract:
Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 +/- 0.45/24 hr (mean +/- SEM), and the duration of episodes was 18.3 +/- 2.8/24 hr. Because of variability over time, the ability to detect significant changes was dependent upon the number of subjects, length of monitoring period, and intervals between monitoring periods. In a clinical trial, for example, a sample size of 25 patients monitored for 48 hours with 1 week between control and test conditions would require a 65% reduction in frequency, whereas a sample size of 50 patients monitored under similar conditions would require a 46% reduction in frequency, to attribute the change with 90% power to a therapeutic intervention rather than to a spontaneous variation. When monitoring a single patient for 48 hours with 1 week or 1 month between control and repeat monitoring sessions, episodes of ischemic ST depression must be eliminated to detect significant therapeutic changes in ischemic activity at the 95% confidence level.(ABSTRACT TRUNCATED AT 250 WORDS)