Ischemia during ambulatory monitoring as a prognostic indicator in patients with stable coronary artery disease
D. Mulcahy, S. Husain, G. Zalos, A. Rehman, N. P. Andrews, W. H. Schenke, N. L. Geller and A. A. Quyyumi
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1650, USA.
OBJECTIVE: To assess long-term prognostic significance of transient
ischemia in patients with documented coronary artery disease and stable
symptoms and to examine the relation between transient ischemia and the
site of angiographic disease progression following acute cardiac events.
DESIGN: Cohort study with a mean+/-SD follow-up of 51.5+/-23.8 months.
SETTING: Ambulatory patients with stable coronary artery disease, assigned
to medical therapy. PATIENTS: A total 221 patients (173 men; mean age, 60.8
years) were recruited. Of the 221 patients, 101 (45.7%) had single-vessel,
86 (38.9%) had 2-vessel, and 34 (15.4%) had 3-vessel disease. A total of
135 had a positive exercise test for ischemia, and mean+/-SD resting left
ventricular ejection fraction (LVEF) was 49.8%+/-11.4%. Using conventional
criteria, patients were prospectively stratified as low risk for continued
medical therapy (single-vessel disease, 2-vessel disease with negative
exercise test, or LVEF> or =40%; n=189 [85.5%]) or high risk for
continued medical therapy (multivessel disease with ischemia and/or left
ventricular dysfunction; n=32 [14.5%]). INTERVENTIONS: Ambulatory
ST-segment monitoring, treadmill exercise testing, radionuclide
ventriculography, and coronary angiography. MAIN OUTCOME MEASURES:
Demographic, clinical, ambulatory monitoring, treadmill exercise, and left
ventricular function variables as independent predictors of acute (cardiac
death, myocardial infarction, or unstable angina) or all (including
revascularization) cardiac events in the overall and the low-risk
population. RESULTS: None of the clinical or noninvasive measures of
ischemia were of prognostic significance in the overall or the low-risk
group. The only significant independent predictor of outcome in all
patients for all events, including revascularization, was the number of
diseased vessels (X2=13.5 [df=1]; P<.001). Exclusion of vessel disease
resulted in conventional risk stratification as the most significant
predictor of outcome from all events in all patients (X2= 10.3 [df= 1];
P=.001). In the low-risk group, the number of diseased vessels was the only
predictor for all events (X2=4.6; P=.03). For acute cardiac events, none of
the variables tested were of prognostic significance. Based on the
frequency of events in the low-risk patients, a 2-fold increase in the rate
of cardiac events in patients with transient ischemia compared with those
without transient ischemia during ambulatory monitoring could be excluded
with greater than 85% power and alpha of .05. Of 30 patients suffering
acute nonfatal cardiac events during follow-up, angiography was performed
in 27, revealing significant progression of coronary disease in 24 (88.8%)
and the development of new significant lesions at sites remote from
previously significant lesions in 20 (74%) cases. These new lesions were
equally likely to occur in those with or without transient ischemia at
initial assessment. CONCLUSIONS: Acute cardiac events in predominantly
low-risk stable angina patients with confirmed coronary disease are
unpredictable, and those more likely to suffer such an event cannot be
identified by the detection of ambulatory ischemia. Acute nonfatal cardiac
events result predominantly from the development of significant new
coronary lesions, not initially severe enough to cause ischemia. Patients
categorized as high risk for long-term medical therapy have an increased
rate of cardiac events (mainly revascularization) when compared with
low-risk patients.
