This is a review addressing the role of exercise stress electrocardiography (ECG) without concomitant cardiac imaging. The following are 10 points to remember:

1. Guidelines. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on exercise testing in the management of stable ischemic heart disease and ACC/AHA appropriate use criteria for cardiac radionuclide imaging recommend exercise stress ECG as the initial diagnostic test among patients at intermediate pretest risk who are able to exercise and who have an interpretable resting ECG.
2. Test accuracy. A meta-analysis of 24,047 patients in 147 studies found exercise ECG to have a pooled sensitivity of 68% and specificity of 77% for detection of coronary artery disease (CAD). Sensitivity was lower (50%) and specificity higher (90%) when analysis was limited to three studies free of workup bias. Confounders such as resting ST-segment depression, digoxin usage, and left ventricular (LV) hypertrophy with repolarization changes decrease specificity, whereas mild single-vessel disease decreases sensitivity.
3. Outcomes. Exercise-induced ST-segment depression is a powerful predictor of adverse cardiac events. In a Duke study of 2,842 patients, maximum ST-segment deviation was the strongest predictor of both cardiac death and a composite of cardiac death and nonfatal myocardial infarction (MI).
4. Additional diagnostic and prognostic tools. Additional variables supplement ST-segment depression and can help add to the diagnostic and prognostic utility of exercise ECG.
   • Exercise capacity. Beyond ST-segment depression, exercise capacity is the most powerful variable that adds to the diagnostic and prognostic utility of exercise ECG. Patients attaining <7 metabolic equivalents (METs) have an 18-fold higher prevalence of substantial (≥10%) LV ischemia compared with those reaching ≥10 METs; patients achieving ≥10 METs have very low rates of cardiac death (0.1%/year) and nonfatal MI (0.7%/year).
   • The pressure-rate product is a surrogate for exercise capacity and helps predict the probability of three-vessel or left main CAD.
   • The Duke Treadmill Score is a composite index that combines multiple predictors into one measure, also carrying diagnostic and prognostic value.
5. ECG findings other than ST-segment depression. Markers other than exercise-induced ST-segment depression have diagnostic and prognostic value.
   • Rapid ST-segment recovery is associated with a low rate of positive imaging or findings of CAD on angiography, and favorable clinical outcomes (using a composite endpoint of cardiovascular death, nonfatal MI, or coronary revascularization) despite a positive exercise treadmill test.
   • The ST/heart rate slope and ST/heart rate index have prognostic power.
   • ≥1 mm ST-segment elevation in lead aVR may identify transmural anterior wall ischemia.
   • Changes in QRS duration, R-wave amplitude, and length of the rate-adjusted QT interval may have diagnostic value.
6. Physiologic markers. Several physiological markers can augment the diagnostic accuracy of exercise ECG, and may have prognostic importance, including heart rate (an impaired chronotropic response) and systolic blood pressure (abnormal systolic blood pressure recovery).
7. Special populations. Some special patient populations merit additional comment.
   • Women. The diagnostic accuracy of exercise ECG is lower in women; the pooled sensitivity and specificity in 3,721 women from 19 studies were 61% and 70%, respectively; compared to 68% and 77%, respectively, in men.
   • Diabetes mellitus. Exercise ECG appears to have similar diagnostic accuracy and prognostic significance in patients with and without diabetes. Although a decision regarding whether to employ imaging during functional testing in diabetic patients should be individualized; the use of cardiac imaging may aid in risk stratification among diabetic patients who are at higher risk (those with poor exercise tolerance, dysfunction, nephropathy, vascular disease, or an abnormal resting ECG).
   • Elderly. Although age is not a consideration in current guidelines for the use of exercise ECG, functional limitations and comorbidities in the elderly lead to a higher rate of conversion to pharmacologic stress imaging.
8. Baseline ECG abnormalities. Several baseline ECG abnormalities affect exercise ECG test performance.
   • Resting ST-segment depression. Resting ST-segment depression <1 mm increases test sensitivity but decreases test specificity, with no change in overall test accuracy.
   • Left bundle branch block (LBBB). Patients with LBBB require cardiac imaging due to a high rate of false-positive exercise ECG.
   • Right BBB (RBBB). The role of exercise stress ECG is less clear in the setting of RBBB.
9. 85% age-predicted maximum heart rate. Because of the late occurrence of ECG changes in the ischemic cascade and known limited test sensitivity of exercise ECG, reaching an adequate workload and heart rate is essential for test accuracy.
10. Novel protocols. Two novel protocols that refine exercise ECG and help reduce the risk of false-negative testing include provisional myocardial perfusion imaging in patients unable to achieve a high exercise workload, and incorporation of coronary calcium scoring.

Keywords: Angina, Stable, Angiography, Blood Pressure, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Tests, Routine, Electrocardiography, Exercise Test, Exercise Tolerance, Metabolic Equivalent, Myocardial Infarction, Myocardial Ischemia, Myocardial Perfusion Imaging

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