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Objective: The goal of this study was to evaluate the very long-term outcome after normal exercise (99m)Tc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). Exercise (99m)Tc-sestamibi SPECT is widely used for risk stratification, but data on very long-term outcome after a normal test are scarce.Methods: A consecutive group of 233 patients (122 men, mean age 54 ± 12 years) with known or suspected coronary artery disease (CAD) underwent exercise (99m)Tc-sestamibi SPECT and had normal myocardial perfusion at exercise and at rest. Follow-up endpoints were all-cause mortality, cardiac mortality, nonfatal myocardial infarction, and coronary revascularization. Predictors of outcome were identified by Cox proportional hazard regression models using clinical and exercise testing variables.Results: During a mean follow-up of 15.5 ± 4.9 years, 41 (18%) patients died, of which 13 were cardiac deaths. A total of 18 (8%) patients had a nonfatal myocardial infarction, and 47 (20%) had coronary revascularization. The annualized event rates for all-cause mortality, cardiac mortality, cardiac mortality/nonfatal infarction, and major adverse cardiac events were, respectively, 1.1%, 0.3%, 0.7%, and 1.8%. Multivariate analysis demonstrated that the variables age, male gender, diabetes, diastolic blood pressure at rest, rate pressure product at rest, peak exercise heart rate, and ST segment changes were independent predictors of major adverse cardiac events.Conclusion: Patients with suspected or known CAD and normal exercise (99m)Tc-sestamibi myocardial perfusion SPECT have a favorable 15-year prognosis. Follow-up should be closer in patients with known CAD, and/or having clinical and exercise parameters indicating higher risk status. [ABSTRACT FROM AUTHOR]