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November 30, 2021 Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 e408 CLINICAL STATEMENTS AND GUIDELINES cardiovascular events.7 Additionally, exercise testing without imaging is also reasonable to perform in low-risk individuals with stable chest pain and no known CAD to exclude myocardial ischemia and assess functional capacity10 (Figure 12). Recommendation-Specific Supportive Text 1. There are several pretest probability scores for use in symptomatic patients with suspected CAD. Older pretest probability scores, such as the Diamond-Forrester model developed in 1979, estimates the probability of obstructive CAD, resulting in significant overestimation in contemporary patients referred for noninvasive imaging, particularly women.1 Newer pretest probability estimates are available.4 The CAD Consortium models include basic (age, sex, symptoms, and hospital setting); clinical (basic model + risk factors: diabetes, hypertension, hyperlipidemia, and smoking); and extended (clinical model + CAC) versions. Each new variant is better than older models, and the addition of variables within each model level improves prediction.3 A major strength of these models is the extensive validation in different hospitals, settings, and countries. Another updated model to estimate the pretest probability of obstructive CAD was recently developed4,22 and has been recommended by the ESC guidelines, further reinforcing that the prevalence of obstructive CAD among symptomatic patients is substantially lower than predicted estimates. 2. Among symptomatic patients, a CAC score of zero identifies a low-risk cohort of patients who may not require additional diagnostic testing; most events occur among patients with detectable CAC (eg, 84% in the PROMISE trial).7,9 Several randomized trials evaluated the role of CAC in guiding selective use of follow-up testing, including CCTA.6,7 From the CRESCENT 1 (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease) trial, 350 symptomatic patients were randomized to CAC scanning versus exercise ECGs.7 Only patients with detectable CAC or high pretest risk (141/242) underwent follow-up CCTA. At 1 year, the CAC arm was associated with a reduction in cardiovascular disease events when compared with those who underwent exercise testing alone (P=0.011). 3. Exercise testing was shown to be an effective diagnostic strategy in low-risk symptomatic women from the WOMEN (What Is the Optimal Method for Ischemia Evaluation in Women) trial, when compared with exercise MPI.10 Using this approach, there was no significant difference in CAD death or hospitalization for an ACS or heart failure, with either test, but exercise testing alone provided significant cost savings. 5.1.3 Intermediate-High Risk Patients With Stable Chest Pain and No Known CAD Recommendations for Intermediate-High Risk Patients With Stable Chest Pain and No Known CAD Referenced studies that support the recommendations are summarized in Online Data Supplements 29 and 30. COR LOE Recommendations Index Diagnostic Testing Anatomic Testing 1 A 1. For intermediate-high risk patients with stable chest pain and no known CAD, CCTA is effective for diagnosis of CAD, for risk stratification, and for guiding treatment decisions.1-12 Stress Testing 1 B-R 2. For intermediate-high risk patients with stable chest pain and no known CAD, stress imaging (stress echocardiography, PET/SPECT MPI or CMR) is effective for diagnosis of myocardial ischemia and for estimating risk of MACE.8,13-35 2a B-R 3. For intermediate-high risk patients with stable chest pain and no known CAD for whom rest/stress nuclear MPI is selected, PET is reasonable in preference to SPECT, if available to improve diagnostic accuracy and decrease the rate of nondiagnostic test results.36-39 2a B-R 4. For intermediate-high risk patients with stable chest pain and no known CAD with an interpretable ECG and ability to achieve maximal levels of exercise (≥5 METs), exercise electrocardiography is reasonable.8,13,15,40-45 2b B-NR 5. In intermediate-high risk patients with stable chest pain selected for stress MPI using SPECT, the use of attenuation correction or prone imaging may be reasonable to decrease the rate of false-positive findings.46-51 Assessment of Left Ventricular Function 1 B-NR 6. In intermediate-high risk patients with stable chest pain who have pathological Q waves, symptoms or signs suggestive of heart failure, complex ventricular arrhythmias, or a heart murmur with unclear diagnosis, use of TTE is effective for diagnosis of resting left ventricular systolic and diastolic ventricular function and detection of myocardial, valvular, and pericardial abnormalities.13,14,52 Sequential or Add-on Testing: What to Do if Index Test Results are Positive or Inconclusive 2a B-NR 7. For intermediate-high risk patients with stable chest pain and known coronary stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA, FFR-CT can be useful for diagnosis of vessel-specific ischemia and to guide decision-making regarding the use of coronary revascularization.12,53-58 2a B-NR 8. For intermediate-high risk patients with stable chest pain after an inconclusive or abnormal exercise ECG or stress imaging study, CCTA is reasonable.5,59-63 2a B-NR 9. For intermediate-high risk patients with stable chest pain and no known CAD undergoing stress testing, the addition of CAC testing can be useful.64-70 Downloaded from http://ahajournals.org by on October 7, 2026