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For 50 years, exercise testing has served as the backbone of the noninvasive evaluation of coronary artery disease (CAD) and as an essential component of a clinician’s tool kit. Its rationale is compelling: it is simple, widely available, and inexpensive. Underused as stand-alone testing, a sophisticated and critical evaluation of the ECG and the patient during exercise and recovery, and a true maximal exercise effort, often provides the test sensitivity required for decision making without adjunctive nuclear or echocardiographic imaging. When adjunctive imaging is used, this same discriminatory power can enhance accuracy and confidence in the combined study.
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When standardized exercise testing was developed by Master and colleagues in 1929,1 the gold standard for exercise test accuracy was the development of angina and the occurrence of cardiac events.2,3 The advent of coronary angiography in 19584 created a new gold standard, easily performed after exercise testing to study the correlation between exercise test results and coronary luminal anatomy. The following year, Prinzmetal and coworkers identified that ischemia could be caused by coronary vasospasm in the presence or absence of obstructive anatomic disease.5 Coronary vasospasm was thought to be infrequent, however, and the accuracy of exercise testing continued to be measured by the presence of obstructive CAD on coronary angiography. A few decades later, the development of thallium- and technetium-based single photon emission computed tomography (SPECT) imaging allowed myocardial perfusion imaging (MPI) to be considered a gold standard.
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Studies assessing the physiologic effect of coronary stenoses with fractional flow reserve (FFR) call the use of coronary angiography to predict ischemia, and thus serve as a gold standard, into question. Meanwhile, recent advances in quantitative positron emission tomography (PET) imaging create the opportunity to accurately measure global myocardial blood flow, and cardiac magnetic resonance imaging (MRI) has been shown to accurately detect ischemia that is solely subendocardial. These two techniques may demonstrate ischemia associated with coronary lesions that are angiographically less than 50% stenotic. Thus, what is the proper gold standard against which exercise testing should be compared? As exercise testing detects ischemia that is predominately subendocardial, the assessment of global coronary flow by quantitative pharmacologic PET or ischemia by cardiac MRI should serve as the new gold standards. If ischemia in the distribution of a particular coronary artery needs to be evaluated, FFR can serve as the gold standard. Our previous understanding of the accuracy of exercise testing to detect ischemia must be tested against these new gold standards. The bulk of the extensive literature assessing the sensitivity and specificity of exercise stress testing used coronary angiography as the gold standard. As such, the basis of our understanding of exercise test sensitivity, specificity, and predictive values may be called into question. As new correlative studies have yet to be performed, we must rely on previous studies to best understand the accuracy of exercise testing, understanding ...