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Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 November 30, 2021 e411 CLINICAL STATEMENTS AND GUIDELINES

4.	 Diagnostic accuracy of the exercise ECG is lower (ie, sensitivity and specificity range, 60%–77%) than stress imaging, but prognostication remains a useful goal.13,41 In the WOMEN trial including 824 symptomatic women, exercise ECG was equally effective when compared with exercise SPECT MPI, with similar 2-year CAD event rates (2.0% versus 2.3%; P=0.59).40 Failure to complete the first stage of the Bruce protocol (or <5 METs) or to achieve 85% of age-predicted fitness level increases CAD event risk.13,41-45 Patients exercising to Bruce stage III or >10 METs with a negative ECG have a low risk of CAD events. In patients with submaximal exercise or for those with an ischemic ECG ≥1.0 mm ST depression, additional stress imaging may improve risk detection and guide clinical management.41 Marked ischemia (eg, ≥2.0 mm at reduced workloads) or high Duke or Lauer scores signify increased risk among women and men13,41,42,44; such patients may benefit from additional testing (anatomic or stress testing). 5.	 Use of attenuation correction algorithms and prone imaging can reduce MPI artifacts.46-51 Assessment of Left Ventricular Function

6.	 Clinical practice guidelines and appropriate use criteria support use of TTE as appropriate for the assessment of regional and global left ventricular function.13,14 The likelihood of abnormal findings increases when TTE is performed selectively among higher risk patients, such as those with electrocardiographic Q waves or heart failure symptoms, complex ventricular arrhythmias, or a heart murmur.52 Sequential or Add-on Testing: What to Do if Index Test Results are Positive or Inconclusive

7.	 The use of FFR-CT is supported by several studies,56,57,104 including one reporting improved diagnostic accuracy with FFR-CT versus coronary CT alone when applying invasive FFR as the gold standard.56 Several multinational registries have examined the utility of FFR-CT with regards to guiding clinical decision-making and the safety of deferring coronary revascularization in patients with a negative FFR-CT.12,26,53,54 In the ADVANCE registry, FFR-CT changed treatment recommendations in two-thirds of 5 083 patients, and there were no MACE at 90 days for patients with a negative FFR-CT.54 FFR-CT is most beneficial when measured in a coronary stenosis of 40% to 90% severity located in a proximal or mid-coronary artery segment.54,106,107 8.	 Use of CCTA after stress testing can diagnose or exclude obstructive CAD and identify patients who may benefit from referral to ICA.5,59-61,63 The ISCHEMIA trial used CCTA after site-determined moderate-severe ischemia to exclude patients with nonobstructive CAD and identifying those with significant left main stenosis who benefit from prompt referral to ICA.63,108 Half of the screen failures for the ISCHEMIA trial were identified by CCTA including those with nonobstructive CAD or unprotected left main CAD. 9.	 Observational registry data suggest that adding

CAC can improve risk assessment, reduce diagnostic uncertainty, help detect atherosclerotic plaque, and guide preventive management.64-70,94,109,110 10.	 After an initial exercise ECG, data support an improved diagnostic accuracy and improved risk stratification with further stress imaging, such as with stress echocardiography,13,14,71,72 nuclear MPI,20-23,40,73-76 or CMR.35,111-113 11.	 For the symptomatic patients with negative stress test findings, selective use of CCTA or invasive coronary angiography can help detect obstructive CAD and atherosclerotic plaque and reduce diagnostic certainty.

5.2 Patients With Known CAD Presenting With

Stable Chest Pain Recommendations for Patients With Known CAD Presenting With Stable Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplement 31.

COR LOE Recommendations

1 A 1.	 For patients with obstructive CAD and stable chest pain, it is recommended to optimize GDMT.1-3

1 C-EO 2.	 For patients with known nonobstructive CAD and stable chest pain, it is recommended to optimize preventive therapies.4,5

Synopsis In patients with known CAD, clinicians should opt to intensify GDMT first, if there is an opportunity to do so, and defer testing. Although GDMT exists for obstructive CAD, there are no current guidelines that are specific to nonobstructive CAD. Thus, adhering to atherosclerotic CV prevention guidelines is recommended.4,5 Recommendation-Specific Supportive Text

1.	 ACC/AHA clinical practice guidelines for treatment of patients with stable CAD recommend optimization of anti-ischemic and preventive therapies with the goal to reduce the patient’s angina burden and improve clinical outcomes.6,7 2.	 For all patients with a history of CAD risk factors, optimized preventive therapy should be used according to ACC/AHA clinical practice guidelines.4,5

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