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Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 November 30, 2021 e395 CLINICAL STATEMENTS AND GUIDELINES

Observations to Study Predictors of Events in the Coronary Tree) trial comparing CCTA- versus MPI-directed strategies (P=0.29).10 Similar 2-year outcomes were also reported for stress echocardiography and CCTA (P=0.47).29 2.	 In patients who have evidence of moderate or severe ischemia on previous stress testing, who were not revascularized, and who present with acute chest pain, additional noninvasive stress testing is unlikely to result in any change in management. Such patients are assumed to have significant flow-limiting CAD and can proceed directly to an invasive evaluation if coronary revascularization is consistent with the goals of care. A sizeable proportion of patients with moderate-severe ischemia do not undergo ICA51,52 and may require additional assessment, if repeat symptoms occur. 3.	 Symptomatic patients with inconclusive or mildly abnormal stress tests often have an increased risk of MACE.53 Patients with previous stress testing often have atherosclerotic plaque and are at risk for obstructive CAD lesions.12,13

Stress Testing

4.	 Among patients evaluated in the ED who need further testing, exercise ECG is safe with most patients having negative studies and a low risk of ACS.1,4,10,14-31,54 Stress echocardiography is safe and effective for triage and prompt discharge of patients and is associated with few events among those with normal or low-risk findings over nearterm follow-up of up to 6 months.17,18,36 Prompt stress echocardiography resulted in a reduction in ED and hospital length of stay, compared with CCTA, with similar 2-year MACE rates (P=0.47).29 In the ED evaluation of patients with acute chest pain, a nuclear MPI strategy is similarly safe when compared with CCTA with no difference in MACE (death, ACS, or stroke) over follow-up of 6 to 12 months. Longer-term follow-up data from the PROSPECT trial10 supported that at ∼3.5 years, the rate of MACE was similar between MPI and CCTA (P=0.29).10 Compared with CCTA, use of stress MPI delayed the time to diagnosis by >50%.1,4 Furthermore, recent observation from 213 patients referred for rest-stress MPI with mildly abnormal hs-cTn values reported no adverse events related to the tests and a modest 13.6% yield for ischemic studies.55 Single-center, small (n=105) randomized trial evidence suggests that stress CMR is safe without a near-term (90-day) increase in hospital readmission or additional testing.32-34 From a single-center registry (n=135), stress CMR was associated with a high sensitivity (100%) and specificity (93%) for the detection of obstructive CAD or cardiovascular events at 1 year.35 Sequential or Add-on Testing

5.	 Patients with coronary artery stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA may benefit from measurement of FFR-CT.37-43 In a large registry of 555 patients, the addition of FFR-CT was safe with no difference in 90-day MACE compared with CCTA alone.42 No deaths or MI occurred among patients with a negative FFR-CT when revascularization was deferred. 6.	 CCTA is highly effective at ruling out the presence of plaque or stenosis and may help to clarify risk assessment and subsequent management decisions in patients with no known CAD who have inconclusive stress test results. 7.	 Patients with acute chest pain who have indeterminate stenosis on CCTA may benefit from having a stress test with imaging to evaluate for myocardial ischemia.37-43 4.1.2.1.1. Cost-Value Considerations Economic evaluations have explored the value of stress echocardiography, CCTA, and stress nuclear imaging. Several observational series report that prompt stress echocardiography in the ED for the evaluation of acute chest pain is associated with significantly lower costs, with no adverse sequelae after early discharge.1,2 In a single-center randomized trial of 400 patients, prompt stress echocardiography was associated with a reduced rate of hospitalization (P=0.026) and length of stay in the ED (P<0.0001).3 The CT-STAT (Systematic Triage of Acute Chest Pain Patients to Treatment) trial reported on the use of CCTA (n=361 patients) compared with stress MPI (n=338 patients) in the acute evaluation of chest pain in the ED.4 In the CT-STAT trial, the time to diagnosis was 2.9 hours in the CCTA arm and 6.2 hours in the stress MPI arm (P<0.0001). Accordingly, median adjusted ED charges were nearly 40% lower for CCTA, compared with stress MPI ($2137 for CCTA versus $3458 for stress MPI; P<0.001). Overall, CCTA resulted in improved efficiency with a reduction in length of stay and prompt discharge,5,6 resulting in cost savings from 15% to 38% when compared with standard care strategies4,7 and a weighted cost savings of $680.8

4.1.2.2 Intermediate-Risk Patients With Acute Chest Pain and Known CAD

Recommendations for Intermediate-Risk Patients With Acute Chest Pain and Known CAD Referenced studies that support the recommendations are summarized in Online Data Supplements 16 and 17.

COR LOE Recommendations

1 A 1.	 For intermediate-risk patients with acute chest pain who have known CAD and present with new onset or worsening symptoms, GDMT should be optimized before additional cardiac testing is performed.1,2

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