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November 30, 2021 Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 e410

CLINICAL STATEMENTS AND GUIDELINES ≥65 years of age, because they have a higher likelihood of ischemia and obstructive CAD.34-36,81-83 Although previous guidelines supported direct referral to ICA among patients with stable chest pain, contemporary randomized trials support that candidates for elective coronary angiography may be safely triaged using CCTA1,84 or noninvasive stress testing.34,35

Patient characteristics and existing contraindications for a given test modality (Tables 5 and 6) should be considered when choosing a diagnostic test. Imaging of obese patients, especially those with morbid obesity (body mass index >40), can be challenging and requires careful consideration of available equipment. In obese patients, contrast enhancement is useful to improve imaging quality. In certain patients, it may be important to undergo exercise testing so to collect data on the hemodynamic or symptomatic response to exercise. In patients selected for stress imaging who are able to exercise, exercise testing is preferred over pharmacologic stress to improve the diagnostic and prognostic information of the test. Although PET and SPECT are grouped together, PET has improved diagnostic and prognostic performance, especially when quantitative assessment of MBF can be performed.36-39 Irrespective of the test performed, an overarching goal of the evaluation of symptomatic patients is to identify those who would benefit from GDMT, as defined by the 2014 SIHD guidelines, the 2018 cholesterol-lowering guidelines, and the 2019 prevention guidelines.13,85-87 For this evaluation, the patient should be engaged in a process of shared decision-making before determining the final choice of the cardiac test modality and in guiding the pathway for treatment decisions.

Recommendation-Specific Supportive Text Anatomic Testing

1.	 Clinical trials report a higher diagnostic sensitivity for CCTA compared with stress testing for detecting obstructive CAD on ICA.2-4,37,38,88 CCTA without stenosis or plaque has a low CAD event rate. From the PROMISE trial, the 3-year CAD event rate for negative test findings was 0.9% for CCTA versus 2.1% for stress testing.17Randomized trials comparing the effectiveness of CCTA versus stress testing report similar near-term effectiveness (at ∼2–3 years of follow-up).7,8,10-12,89 In the SCOT-HEART (Scottish Computed Tomography of the Heart) trial, the addition of CCTA to standard of care resulted in a reduction in 5-year CAD death or AMI when compared with standard care alone (predominantly exercise ECG) (HR: 0.59; 95% CI: 0.41-0.84; P=0.004).9 From a prespecified analysis from the PROMISE trial, patients with diabetes who underwent CCTA had a lower risk of cardiovascular death or MI when compared with those randomized to stress testing (adjusted HR: 0.38; 95% CI: 0.18-0.79; P=0.01).6 Especially for patients with nonobstructive and obstructive CAD, CCTA more often prompts initiation and intensification of preventive and anti-ischemic therapies than other diagnostic strategies.6,89-96 Several randomized trials compared the effectiveness of CCTA versus direct referral to ICA among symptomatic patients.1,5 From the CONSERVE trial, a strategy of initial CCTA was associated with lower cost but similar 1-year MACE rates (death, ACS, stroke, urgent/emergency coronary revascularization, or cardiac hospitalization) as direct ICA (4.6% versus 4.6%).5

Stress Testing

2.	 The prognostic value of stress echocardiography has been demonstrated in large observational series with low rates of CAD events for patients with normal test results, particularly those with good exercise tolerance.71,72,97-99 In the PROMISE trial, patients randomized to stress testing had no difference in the primary outcome of death, ACS, or major procedural complications as compared to CCTA.100 For stress nuclear imaging, multicenter registries support effective risk stratification based on rest/stress measures of MPI and left ventricular function,13,21,27,28,98,101,102 with recent evidence on the prognostic value of stress PET.26,37,38,103,104 Randomized trials have compared the effectiveness of rest/stress MPI with other noninvasive tests, such as CMR105 and CCTA, revealing similar 1- to 3-year outcomes. Two multicenter trials have evaluated the effectiveness of a CMR-guided strategy as compared to standard testing approaches.34,35 The CE-MARC 2 multicenter trial (n=1 202) revealed that both CMR and SPECT MPI were associated with similar rates (ie, 7.1%–7.5%) of unnecessary invasive angiography (defined as a no CAD stenosis ≥70% or a normal invasive FFR) compared with standard testing for chest pain (28.8%; P<0.001).34 The MR-INFORM trial randomized 918 patients with typical angina and multiple risk factors or a positive exercise ECG to a CMR strategy versus invasive FFR strategy.35 The CMR strategy was associated with less coronary revascularization (P=0.005) and a similar event rate (death, AMI, or target vessel revascularization; P=0.91). 3.	 Although PET and SPECT are grouped together, PET has improved diagnostic and prognostic performance, especially when quantitative assessment of MBF can be performed.36-39 A recent clinical trial (n=475) reported a higher diagnostic accuracy with stress PET MPI compared with other stress test modalities.38

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