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This study was designed to evaluate the prognostic value of symptom-limited maximal exercise treadmill testing with tomographic technetium-99m sestamibi (MIBI) myocardial imaging in patients referred for evaluation of stable angina. Exercise stress thallium-201 myocardial imaging provides prognostic information in coronary artery disease subsets including patients with stable chest pain. The prognostic value of exercise technetium-99m MIBI myocardial tomography has not been established.Of 548 consecutive patients with stable angina pectoris who underwent maximal exercise treadmill stress testing in combination with a same-day “rest-stress” tomographic technetium-99m MIBI myocardial imaging protocol, 521 patients were followed for 13±5 months to determine the univariate and multivariate variables associated with cardiac events and to define their cardiac event-free survival. Ten patients were lost to follow-up (98% complete), and 17 who had coronary revascularization within 6 months of testing were excluded. Major cardiac events occurred in 24 patients (9%) –nonfatal myocardial infarction in 11 and cardiac death in 13. Univariate Cox survival analysis demonstrated significant relative risk (RR) and 95% confidence intervals (CI) for exercise ST segment depression (RR=2.3; 95% CI, 1.0 to 5.3), an abnormal MIBI scan (RR=13.8; 95% CI, 1.9 to 102.3), and a reversible MIBI perfusion defect (RR=3.2; 95% CI, 1.4 to 7.5). Multivariate models demonstrated that both exercise MIBI perfusion abnormalities (RR= 11.9; 95% CI, 1.6 to 89.4) and reversible MIBI perfusion defects (RR=2.9; 95% CI, 1.2 to 7.0) had independent predictive value. During 1 year of follow-up, cardiac events occurred in only 0.5% of patients with normal MIBI scans compared with 7% of those with abnormal MIBI scans (P < .001). One-year, cardiac event-free survival was 92% in patients with reversible MIBI perfusion defects (P < .01 versus normal), 96% in patients with fixed defects (P < .01), and 93% in patients with combined reversible and fixed MIBI myocardial perfusion abnormalities (P < .02).As with exercise thallium-201 myocardial imaging, exercise stress technetium-99m MIBI myocardial tomography provides significant independent information concerning the subsequent risk of serious cardiac events (death, myocardial infarction) in patients with stable angina pectoris. The identification of MIBI perfusion abnormalities, in particular, the presence of reversible MIBI defects, was associated with reduced 1-year, event-free survival. The recognized imaging and radiotracer biokinetic differences between thallium- 201 and MIBI do not appear to modulate the prognostic value associated with scintigraphic evidence of ischemic myocardial jeopardy in the stable angina population.