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In the past three decades, a great body of literature has established the use of radionuclide myocardial perfusion imaging (MPI), for risk stratification in patients with known or suspected coronary artery disease (CAD). The early studies have been reinforced and enhanced with the use of novel stress agents, modern single-photon emission tomography (SPECT) technologies, and the evolution of the appropriate use criteria (AUC). This chapter will review the use of stress radionuclide SPECT MPI for risk stratification in a general population and among patients with chronic CAD. Risk stratification for specific applications is discussed elsewhere in this book, including prior to major noncardiac surgery (Chapter 16), after therapeutic intervention (Chapter 17), in heart failure patients (Chapter 18), and for a variety of unique populations (Chapter 19).

Risk Assessment

Risk stratification is of crucial importance for the practice of contemporary medicine. Appropriate management of CAD should include the assessment of the individual risk of future cardiac events, particularly cardiac death and myocardial infarction (MI).1 Extending the paradigm of noninvasive cardiac testing beyond the detection of disease is especially important, as risk assessment permits patient management decisions to be formulated on an evidence-based approach. Patients who are identified as being at high risk for subsequent cardiac events should be considered for aggressive management, including cardiac catheterization and revascularization procedures that may improve their outcome. Conversely, the management of low-risk patients should be focused toward aggressive medical therapy and risk factor modification,2,3 thus reserving invasive procedures for patients who fail medical management. Additional testing in this low-risk group should generally be avoided, thereby minimizing cost. An outcome-based risk assessment model strives for improved patient outcome and avoidance of complications from unnecessary procedures, and is cost-effective.

Risk strata are often defined in many ways; but when related to CAD events, specifically nonfatal MI and cardiac death, an annual event rate of <1% is accepted as a low risk, while an annual event rate of >3% is considered high risk and an annual event rate between 1% and 3% is an intermediate risk.4

Risk can be defined using clinical parameters, namely cardiac risk factors5 and symptoms characterization, such as chest pain4 or dyspnea.6 However, risk assessment based only on clinical findings and resting ECG is often limited. Exercise tolerance test (ETT) without imaging and related risk indices, such as the Duke Treadmill Score, provide substantial prognostic value.7 Unfortunately, in contemporary practice, many patients cannot undergo ETT due to aging, obesity, and other limiting comorbidities. Moreover, using clinical data and the Duke Treadmill Score, most patients with suspected CAD would fall in an intermediate-risk group which may necessitate additional risk stratification.8

While coronary angiography is considered the "gold standard" for the diagnosis of CAD, it does not provide information about the physiologic significance of atherosclerotic disease, especially in borderline lesions (50–70% stenosis) or when the culprit lesion ...

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