2021 AHA／ACC／ASE／CHEST／SAEM／SCCT／SCMR指南：胸痛的诊断和评估（全文）

指南麻醉与急重症· 急诊与复苏 · 2021

Authors

Keywords

eXXX 3.2.2. Echocardiography/Stress Echocardiography . . . . . . . . . . . . . . . eXXX 3.2.3. Stress Nuclear (PET or SPECT) Myocardial Perfusion Imaging . . . . . eXXX 3.2.4. Cardiovascular Magnetic Resonance Imaging . . . . . . . . . . . . . eXXX 3.3. Cardiac Testing Considerations for Women Who Are Pregnant, Postpartum, or of Child-Bearing Age . . . . . . . . . . . . . . . . eXXX 4. Choosing the Right Pathway With Patient-Centric Algorithms for Acute Chest Pain . . . . . . . eXXX 4.1. Patients With Acute Chest Pain and 5.2.1. Patients With Obstructive CAD Who Present With Stable Chest Pain . . . . . eXXX 5.2.1.1. Patients With Prior Coronary Artery Bypass Surgery With Stable Chest Pain . . . . . . eXXX 5.2.2. Patients With Known Nonobstructive CAD Presenting With Stable Chest eXXX 5.2.3. Patients With Suspected Ischemia and No Obstructive CAD (INOCA) . . . eXXX 5.3. Cost-Value Considerations in Diagnostic mitral valve stenosis, multidetector computed tomography, myocardial infarction, myocardial ischemia, myocardium, NT-proBNP, perfusion imaging, positron-emission tomography, pulmonary hypertension, stable angina, troponin I, troponin T, unstable angina, x-ray computed tomography

The ACC/AHA Joint Committee on Clinical Practice Guidelines (Joint Committee) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations, including the Institute of Medicine, 1, 2 and on the basis of internal reevaluation. Similarly, presentation and delivery of guidelines are reevaluated and modified in response to evolving technologies and other factors to optimally facilitate dissemination of information to healthcare professionals at the point of care. Numerous modifications to the guidelines have been implemented to make them shorter and enhance "user friendliness. " Guidelines are written and presented in a modular, "knowledge chunk" format, in which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text and, when

# CLINICAL STATEMENTS AND GUIDELINES

appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review.

In recognition of the importance of cost-value considerations, in certain guidelines, when appropriate and feasible, an analysis of value for a drug, device, or intervention may be performed in accordance with the ACC/ AHA methodology. 3 o ensure that guideline recommendations remain current, new data will be reviewed on an ongoing basis by the writing committee and staff. Going forward, targeted sections/knowledge chunks will be revised dynamically after publication and timely peer review of potentially practice-changing science. The previous designations of "full revision" and "focused update" will be phased out. 6] [7] The Class of Recommendation (COR) indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The Level of Evidence (LOE) rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 1 ). 8

# Selection of Writing Committee Members

Selection of Writing Committee Members

The Joint Committee strives to ensure that the guideline writing committee contains requisite content expertise and is representative of the broader cardiovascular community by selection of experts across a spectrum of backgrounds, representing different geographic regions, sexes, races, ethnicities, intellectual perspectives/biases, and clinical practice settings. Organizations and professional societies with related interests and expertise are invited to participate as partners or collaborators.

# Evidence Review and Evidence Review Committees

Evidence Review and Evidence Review Committees

In developing recommendations, the writing committee uses evidence-based methodologies that are based on all available data. 4, 5 Literature searches focus on ran-domized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinions. Only key references are cited.

1. INTRODUCTION 1.Methodology and Evidence Review

The recommendations listed in this guideline are, whenever possible, evidence based. An initial extensive evidence review, which included literature derived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline, was conducted from November 11, 2017, to May 1, 2020. Key search words included but were not limited to the following: acute coronary syndrome, angina, angina pectoris, aortic valve stenosis, biomarker, biomarkers, brain natriuretic peptide, cardiac-gated single photon emission computer-assisted tomography, cardiovascular magnetic resonance, chest pain, CKMB, coronary angiography, coronary arteriosclerosis, coronary artery disease, creatine kinase, creatine kinase MB, echocardiography, electrocardiography, heart valve disease, hypertrophic cardiomyopathy, magnetic resonance imaging,

1.2. Organization of the Writing Committee

The writing committee consisted of cardiac intensivists, cardiac interventionalists, cardiac surgeons, cardiologists, emergency physicians, epidemiologists, and a lay/patient representative. The writing committee included representatives from the ACC, AHA, American Society of Echocardiography (ASE), American College of Chest Physicians (CHEST), Society for Academic Emergency Medicine (SAEM), Society of Cardiovascular Computed Tomography (SCCT), and Society for Cardiovascular Magnetic Resonance (SCMR). Appendix 1 lists writing committee members' relevant RWI. For the purposes of full transparency, the writing committee members' comprehensive disclosure information is available in the Supplemental Appendix.

CLINICAL STATEMENTS AND GUIDELINES

1.4.2. Defining Chest Pain

Recommendations for Defining Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplements 1 and 2.

COR LOE Recommendations 1 B-NR

1. [3] [4] [5] [6] [7] 1 C-LD 2. Chest pain should not be described as atypical, because it is not helpful in determining the cause and can be misinterpreted as benign in nature. Instead, chest pain should be described as cardiac, possibly cardiac, or noncardiac because these terms are more specific to the potential underlying diagnosis.

Although the term chest pain is used in clinical practice, patients often report pressure, tightness, squeezing, heaviness, or burning. In this regard, a more appropriate term is "chest discomfort, " because patients may not use the descriptor "pain. " They may also report a location other than the chest, including the shoulder, arm, neck, back, upper abdomen, or jaw. Despite individual variability, the discomfort induced by myocardial ischemia is often characteristic and therefore central to the diagnosis. For this reason, features more likely to be associated with ischemia have been described as typical versus atypical; however, the latter can be confusing because it is frequently used to describe symptoms considered nonischemic as well as noncardiac. 4] [5] [6] [7] Pain-described as sharp, fleeting, related to inspiration (pleuritic) or position, or shifting locations-suggests a lower likelihood of ischemia.

Synopsis

Chest pain or chest pain equivalent will be referred to in these guidelines as "chest pain. " Patients presenting to the ED with nontraumatic chest pain are a frequent diagnostic challenge. 1 The priorities are: 1) rapid initiation of optimal management in patients with life-threatening conditions such as ACS, aortic dissection, and pulmonary embolism (PE), as well as nonvascular syndromes (eg, esophageal rupture, tension pneumothorax); and 2) deliberate therapy for those with less critical illness. ] [4] The initial ECG is important to the evaluation, but history, examination, biomarkers, and other aids remain essential. There is frequently a lack of correlation between intensity of symptoms and seriousness of disease and general similarity of symptoms among different causes of chest pain. A comprehensive history that captures all the char-acteristics of chest pain (Table 3 ), including but not limited to its: 1) nature; 2) onset and duration; 3) location and radiation; 4) precipitating factors; 5) relieving factors; and 6) associated symptoms can help better identify potential cardiac causes and should be obtained from all patients.

Recommendation-Specific Supportive Text 1. Angina pectoris is perceived as a retrosternal chest discomfort that builds gradually in intensity (over several minutes), is usually precipitated by stress (physical or emotional) or occurring at rest (as in the case of an ACS) with characteristic radiation (eg, left arm, neck, jaw) and its associated symptoms (eg, dyspnea, nausea, lightheadedness). When actively treated or spontaneously resolving, it dissipates over a few minutes. Relief with nitroglycerin is not necessarily diagnostic of myocardial ischemia and should not be used as a diagnostic criterion, especially because other entities demonstrate comparable response (eg, esophageal spasm). 1, 5 Associated symptoms such as shortness of breath, nausea or vomiting, lightheadedness, confusion, presyncope or syncope, or vague abdominal symptoms are more frequent among patients with diabetes, women, and the elderly. A detailed assessment of cardiovascular risk factors, review of systems, past medical history, and family and social history should complement the assessment of presenting symptoms.

CLINICAL STATEMENTS AND GUIDELINES

2.1.1. A Focus on the Uniqueness of Chest Pain in Women

Recommendations for a Focus on the Uniqueness of Chest Pain in Women Referenced studies that support the recommendations are summarized in Online Data Supplements 3 and 4.

COR LOE Recommendations

1. Traditional risk score tools and physician assessments often underestimate risk in women and misclassify them as having nonischemic chest pain. 1, 2 The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial looked at sex differences in the presentation, risk factors, demographics, noninvasive test referrals, and results of 10 003 stable outpatients with suspected CAD. 1 Women commonly presented with chest pain symptoms similar to men but also had a greater prevalence of other symptoms such as palpitations, jaw and neck pain, as well as back pain. Women also had more cardiovascular risk factors, including hypertension (66 Physician assessments often misclassify chest pain as nonanginal. The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial reported that women with diabetes had a higher prevalence of angina than their male counterparts, with a lower functional capacity and a lower incidence of obstructive CAD. 16 . In the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, men and women ≤55 years of age were equally likely to present with chest pain (defined as pain, pressure, tightness, discomfort; 89.5% versus 87%, respectively). Women were more likely to report ≥3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain or Sharp chest pain that increases with inspiration and lying supine is unlikely related to ischemic heart disease (eg, these symptoms usually occur with acute pericarditis).

Onset and duration

Anginal symptoms gradually build in intensity over a few minutes.

Sudden onset of ripping chest pain (with radiation to the upper or lower back) is unlikely to be anginal and is suspicious of an acute aortic syndrome.

Fleeting chest pain-of few seconds' duration-is unlikely to be related to ischemic heart disease.

Location and radiation

Pain that can be localized to a very limited area and pain radiating to below the umbilicus or hip are unlikely related to myocardial ischemia.

Severity

Ripping chest pain ("worse chest pain of my life"), especially when sudden in onset and occurring in a hypertensive patient, or with a known bicuspid aortic valve or aortic dilation, is suspicious of an acute aortic syndrome (eg, aortic dissection).

2.1.2. Considerations for Older Patients With Chest Pain

Increased age is a significant risk factor for ACS. However, it is also a risk factor for comorbidities that are associated with alternative diagnoses associated with chest pain. As a result, a more extensive diagnostic workup is required in older patients. Although patients > 75 years of age account for 33% of all cases of ACS, alternative diagnoses are still more common than a cardiac cause of chest pain at presentation. Recommendation-Specific Supportive Text

1 C-LD

2. Among patients of diverse race and ethnicity presenting with chest pain in whom English may not be their primary language, addressing language barriers with the use of formal translation services is recommended.

Synopsis

There are marked racial and ethnic disparities when triaging patients who present for the evaluation of chest pain. 2] [3] [4] Similar treatment disparities are found with Hispanic patients and those who are covered by Medicaid or are uninsured. Derived from a nationally representative sample from the National Hospital Ambulatory Health Care Survey reflecting an estimated 78 million ED visits in the United States over a 10-year period, these findings have been unchanged over time. 5 Such disparity in the management of chest pain among diverse population subgroups contributes to worse outcomes, including the greater incidence of AMI and fatal coronary events seen in these key population subgroups. 6, 7 [10] [11] Consideration of race and ethnicity in the evaluation of patients with suspected ACS and in the outpatient evaluation of symptomatic patients is paramount to improving outcomes. Cultural competency training of providers is recommended to address health disparities in the evaluation and management of diverse patient population subgroups with chest pain.

3. CARDIAC TESTING GENERAL CONSIDERATIONS

For acute and stable chest pain, noninvasive and invasive diagnostic testing is a core component of the evaluation underpinning its importance. Over the past decade, the quality of evidence supporting clinical indications for noninvasive testing has grown dramatically. The approach outlined in this guideline focuses on selective use of testing, optimization of lower cost evaluations, reducing layered testing, and deferring or eliminating testing when the diagnostic yield is low (Figure 5 ). Reducing unnecessary testing can provide a means to exert cost savings within the diagnostic evaluation of populations. 1 In the same manner, elimination of testing where evidence is lacking and the reduction in testing among low-risk patients for whom deferred testing is appropriate are emphasized in this guideline. Testing choice will be influenced by site expertise and availability, but knowledge regarding which test may be preferable is useful when selecting between different modalities. Cost should also be considered, when known by the ordering clinician and there is equipoise between available modalities. 2 The exercise ECG is the lowest cost procedure used in the diagnostic evaluation when compared with stress imaging or anatomic procedures, with the exception of coronary artery calcium (CAC) scoring (Figure 6 ). For all imaging procedures, costs vary by payer and site of services.

The following sections provide a brief overview of the various noninvasive tests available for use in the evaluation of symptomatic patients. Previously, the term known as CAD had been used to define those with a significant obstructive stenosis (ie, ≥50%). In this guideline, we revise the term known CAD to include patients with prior anatomic testing (invasive angiography or coronary computed tomographic angiography [CCTA]) with identified nonobstructive atherosclerotic plaque and obstructive CAD. We recognize this is a departure from convention, but our intent was to ensure that those with lesser degrees of stenosis who do not require coronary intervention but would benefit from optimized preventive therapy do not get overlooked. However, throughout the docu-

CLINICAL STATEMENTS AND GUIDELINES

ment, the term "obstructive, " consistent with convention, will be used to indicate CAD with ≥50% stenosis and nonobstructive CAD will be used to indicate CAD < 50% stenosis. In addition, the term "high risk CAD" is used to denote patients with obstructive stenosis who have left main stenosis ≥50% or anatomically significant 3-vessel disease (≥70% stenosis).

3.1. Anatomic Testing

3.1.1. Coronary Computed Tomography Angiography

] [3] [4] [5] [6] [7] [8] Calculation of fractional flow reserve with CT (FFR-CT) provides an estimation of lesion-specific ischemia. 9 Current radiation dosimetry is low for CCTA, with effective doses for most patients in the 3 to 5 mSv range. 10 CTA contraindications are reported in Table 5 Although in select situations imaging protocols that evaluate the coronary arteries, aorta, and pulmonary arteries may be useful, the general approach should be to use imaging protocols tailored to the most likely diagnosis, rather than a "triple rule out" approach (Figure 6 ).

3.1.2. Invasive Coronary Angiography

Invasive coronary angiography (ICA) defines the presence and severity of a luminal obstruction of an epicardial coronary artery, including its location, length, and diameter, as well as coronary blood flow. 1, 2 For ICA, the primary goal is the characterization and detection of a high-grade obstructive stenosis to define feasibility and necessity of percutaneous or surgical revascularization. The use of physiologic indices (IFR and FFR) provides complementary functional information. 1 Radiation exposure to the patient during an interventional procedure averages 4 to 10 mSv and is dependent on procedural duration and complexity. 3, 4 CA has a spatial resolution of 0.3 mm; as such, it is impossible to visualize arterioles (diameter of 0.1 mm) that regulate myocardial blood flow. 5 Coronary vascular functional studies can be performed during coronary angiography. Normal angiography does not exclude abnormal coronary vascular function, and it is possible to assess coronary microcirculation and coronary vaso-

motion. [8] 3.2. Diagnostic Testing

3.2.1. Exercise ECG

Symptom-limited exercise ECG involves graded exercise until physical fatigue, limiting chest pain (or discomfort), marked ischemia, or a drop in blood pressure occurs. 1 Candidates for exercise ECG are those: a) without disabling comorbidity (eg, frailty, marked obesity [body mass index > 40 kg/m 2 ], peripheral artery disease, chronic obstructive pulmonary disease, or orthopedic limitations) and capable of performing activities of daily living or able to achieve ≥5 metabolic equivalents of exercise (METs) 2 ; and b) without rest ST-T abnormalities (eg, > 0.5-mm ST depression, left ventricular hypertrophy, paced rhythm,

left bundle branch block, Wolff-Parkinson-White pattern, or digitalis use). Exercise electrocardiographic contraindications are reported in Table 5 .

3.2.2. Echocardiography/Stress Echocardiography

Transthoracic echocardiography (TTE) can visualize and aid in the differential diagnosis among the numerous causes of acute chest pain such as acute aortic dissection, pericardial effusion, stress cardiomyopathy, and hypertrophic cardiomyopathy. 1, 2 Although TTE does provide information, for patients with acute chest pain, visualization of left and right ventricular function and regional wall motion abnormalities allows for the assessment of CAD risk and may help to guide clinical decision-making. Performance of TTE at the bedside is ideal for patients with acute chest pain and can be done using point-of-care or handheld devices in institutions where such capabilities are available.

3.2.3. Stress Nuclear (PET or SPECT) Myocardial Perfusion Imaging

6] [17] SPECT/PET contraindications are and contraindications to type of stress test (exercise versus pharmacologic) are reported in Table 5 .

3.2.4. Cardiovascular Magnetic Resonance Imaging

Cardiovascular magnetic resonance (CMR) imaging has the capability to accurately assess global and regional left and right ventricular function, detect and localize myocardial ischemia and infarction, and determine myocardial viability. CMR can also detect myocardial edema and microvascular obstruction, which can help differentiate acute versus chronic MI, as well as other causes of acute chest pain, including myocarditis. CMR contraindications are reported in Table 5 .

3.3. Cardiac Testing Considerations for Women Who Are Pregnant, Postpartum, or of Child-Bearing Age

4. CHOOSING THE RIGHT PATHWAY WITH PATIENT-CENTRIC ALGORITHMS FOR ACUTE CHEST PAIN

After initial evaluation, the next step is determining whether further diagnostic testing is needed to establish a diagnosis or formulate a disposition plan. In some cases, there is clearly minimal risk of a serious medical condition although, in others, uncertainty may remain. We provide guidance to help clinicians make this determination within the context of acute and stable chest pain presentations.

1 B-NR

2. In the evaluation of patients presenting with acute chest pain and suspected ACS for whom serial troponins are indicated to exclude myocardial injury, recommended time intervals after the initial troponin sample collection (time zero) for repeat measurements are: 1 to 3 hours for high-sensitivity troponin and 3 to 6 hours for conventional troponin assays. 15 -17

3. To standardize the detection and differentiation of myocardial injury in patients presenting with acute chest pain and suspected ACS, institutions should implement a CDP that includes a protocol for troponin sampling based on their particular assay. 18, 19 [22] [23] [24] 2a B-NR 5. [27] [28] [29]

Patients with acute chest pain and suspected ACS cover a spectrum of disease likelihood and stratification into lowversus intermediate-or high-risk groups once STEMI has been excluded (Figure 8 ). This stratification is important to guide subsequent management. Although most high-risk patients identified by CDPs should undergo cardiac catheterization, these patients still require a clinical assessment to determine if invasive evaluation is appropriate. 1] [32] [33] [34] [35] Risk scores are essential when conventional cTn assays are used. ] [38] [39] [40] [41] [42] [43] Chest pain protocols are intended to add structure to the process of patient evaluation. Although various terms such as accelerated diagnostic protocols or disposition pathways have been used to describe such protocols, they can collectively be referred to as CDPs. CDPs are generally used to help guide disposition, but some also include guidance for cardiac testing of intermediate-risk patients. 30, 31, 33, 34 ompared with an unstructured clinical assessment, CDPs have been shown to decrease unnecessary testing and reduce admissions while maintaining high sensitivity for detection of acute myocardial injury and 30-day MACE (Table 6 ). The warranty period of prior cardiac test-ing should be considered when symptoms are unchanged (Table 7 ). Low-risk chest pain has been defined in Table 8 .

Recommendation-Specific Supportive Text

] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Use of unstructured assessment for clinical decision-making often leads to both under-and over-testing. To improve on this, protocols have been developed to rapidly detect (rule in) and to rapidly exclude or "rule out" acute myocardial injury, incorporating time-dependent serial cTn sampling. Some protocols include chest pain risk scores while others do not. CDPs have been shown to help avoid admission or further testing in 21.3% to 43% of eligible patients and should be routinely used in clinical practice. 31, 45, 50 To standardize the approach to patient care and ensure consistency in decision-making, CDPs should be implemented at the institution level. There are multiple CDPs from *The terms "very low, " "low, " "high, " "1 h Δ, " and "2 h Δ" refer to hs-cTn assay-specific thresholds published in the ESC guideline. 46, 47

which to choose, and all generally involve single or serial cTn measurement. Because there are several different manufacturers, the CDP should be based on assay-specific performance thresholds. 4, 5 CDPs are more likely to be successful when they incorporate multidisciplinary teams. 2. There are important differences in the performance of highly sensitive and conventional cTn assays. 8] [39] [40] [41] [42] [43] When using conventional cTn assays, the sampling timeframe is extended to 3 to 6 hours from ED arrival. 36 . CDPs that include risk scores all perform well overall, with 99% to 100% sensitivity for index-visit AMI and 30-day MACE and have been shown to decrease advanced testing to varying degrees and should be used particularly with conventional cTn. 2, 13, [30] [31] [32] [33] [34] [35] However, because sex-specific considerations are not included in all scoring systems, their effectiveness in men and women may not be equal. 51 4. Previous test results should always be considered in the evaluation of patients with acute chest pain once ACS has been ruled out. Recommendation-Specific Supportive Text [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Although achieving this with conventional cTn assays requires incorporation of risk scores into a CPD, hs-cTn results can be used on their own. This approach has been validated based on 15 studies including a total of > 9 600 patients, with a demonstrated negative predictive value for MI or death at 30 days of 99.8%. 11 These findings reflect studies involving both hs-cTnI and hs-cTnT using serial measurement algorithms or a single hs-cTn, provided the final measurement is performed ≥3 hours after the onset of symptoms, without incorporation of risk scores. 2. For this low-risk subset of ED patients who have chest pain, there is no evidence that stress testing or cardiac imaging within 30 days of the index ED visit improves their outcomes. 18 This represents a change from previous guidelines where stress testing within 72 hours was broadly recommended for patients with acute chest pain. 19 However, many of these patients have baseline cardiac risk factors that need to be managed. Pathways to facilitate outpatient follow-up for further evaluation and guideline-directed management of cardiac risk factors should be considered. Among patients presenting to the ED with chest pain, there is a separate group that is at such low risk of having atherosclerotic plaque or 30-day MACE that they do not even need CDP-based risk stratification.

##### 4.1.1.1. Cost-Value Considerations in the Evaluation of Low-Risk Patients

4.1.1.1. Cost-Value Considerations in the Evaluation of Low-Risk Patients

] [3] [4] [5] [6] [7] [8] [9] [10] The decision analytic models suggest that the use of hs-Tn can be cost effective as a rule-out for ACS, primarily attributable to prompt discharge of patients without hs-Tn elevations. 2, 8, 11, 12 Moreover, hs-Tn-guided diagnostic strategies also reduced the use of stress testing by nearly one-third. 13 rom a large multicenter registry, the reduced time to discharge and use of noninvasive testing contributed to a cost savings of 20%. 13 Nonadherence to management recommendations impact the potential for cost savings. 5 From a randomized trial applying the HEART Pathway, a modest 30-day cost savings of $216 per patient (P=0.04) was observed. 6 However, the overall reductions in hospital admission and length of stay impacted population estimates for cost savings from 1 ED registry of 30 769 patients presenting before and 23 699 patients presenting after implementation of an accelerated diagnostic pathway and resulted in a total cost reduction of $13.5 million (Australian). 7 Thus, improved process efficiency and discharge of low-risk patients largely results in overall cost reductions.

##### Synopsis

Patients in the ED without high-risk features and not classified as low risk by a CDP fall into an intermediate-risk group. Intermediate-risk patients do not have evidence of acute myocardial injury by troponin but remain candidates for additional cardiac testing. Some may have chronic or minor troponin elevations. This testing often requires more time than is appropriate for an ED visit. These patients may be placed in an inpatient bed or managed in a dedicated observation unit using a chest pain protocol.

##### Recommendation-Specific Supportive Text

] [10] [11] [12] [13] Rapid echocardiographic assessment may facilitate imaging of patients while they are symptomatic. Point-of-care echocardiograms performed at the

##### CLINICAL STATEMENTS AND GUIDELINES

bedside by properly trained clinicians and technicians may be particularly useful.

2. The additional testing needed for intermediate-risk

patients often requires more time than is appropriate for an ED visit and is often performed under "observation" outpatient status. These patients may be placed in an inpatient bed or managed in a dedicated observation unit. Relative to care in an inpatient bed, dedicated observation units have been shown to decrease hospital admissions, length of stay, and cost while improving inpatient bed availability and chest pain patient satisfaction.

For patients with recent prior testing and normal findings, no further testing is indicated, given adequate exercise levels were achieved or pharmacologic stress was performed and if imaging was of sufficient quality, provided there are no changes in symptom frequency or stability at the new visit. ] [46] With a previously inconclusive or mildly abnormal stress test in the past year, CCTA is recommended, avoiding the potential for inconclusive results if the same type of test is repeated and enabling a more definitive ruleout of obstructive CAD. Among patients who present with acute chest pain who have had moderate-severe abnormalities on previous testing, but no interval anatomic testing, direct referral to ICA may be helpful for diagnosis of obstructive CAD. Among those without a previous diagnostic evaluation and no known CAD, CCTA or stress testing may be the initial method of testing. Second-line testing may be helpful for patients with an initial inconclusive stress test. Similarly, for intermediate-risk patients with an intermediate stenosis on CCTA, FFR-CT, or stress testing may also be indicated.

ICA is indicated for patients categorized as high risk on a validated risk score (Figure 9 ). However, patients with an intermediate-risk score may also be candidates for CCTA or ICA if moderate-severe ischemia or significant left ventricular dysfunction is detected on index diagnostic testing.

Patients with previous stress testing often have atherosclerotic plaque and are at risk for obstructive CAD lesions. 12, 13 ress Testing 4. 16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [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 n 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 trial 10 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 urthermore, 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 3] [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 8] [39] [40] [41] [42] [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. 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 strategies 4, 7 and a weighted cost savings of $680. 8

Figure 10 includes the evaluation algorithm for patients with known CAD, including patients with nonobstructive and obstructive CAD. In patents with known nonobstructive CAD (ie, a luminal stenosis 1% to 49% on CCTA or ICA or calcified plaque on chest CT), repeat CCTA is recommended unless there is a large enough plaque burden where ischemia is suspected. The use of FFR-CT may be helpful to guide clinical decision-making regarding the use of coronary revascularization. 16 For all other patients with known CAD, stress testing is recommended to guide decisions on optimizing medical management and revascularization.

2. ICA is an effective means for diagnosing obstructive CAD and guiding the use of coronary revascularization. For the intermediate-risk patients with a previous history of CAD, ICA is reasonable for patients presenting with frequent weekly or daily symptoms or for those already on GDMT as well as those with high-risk CAD (left main or proximal left anterior descending or multivessel CAD).

11] 24 Patients in this category also include those patients with a previous CAC scan (or those for whom coronary artery calcification was

noted as an incidental finding on chest CT) who present to an ED for evaluation of chest pain where concern exists with regard to the extent of noncalcified plaque and potential for underlying obstructive stenosis. However, for patients with extensive plaque, a stress test is preferred. 4] [15] [16] [17] 25 From 1 large clinical registry, the deferral of coronary revascularization with a normal FFR-CT was safe, with no difference in MACE at 90 days. 16 . 9] [20] Despite this, assessing the functional significance of obstructive CAD is an important part of ischemia-guided management. 26 1.

Patients with symptoms suggestive of ACS who are at high risk of short-term MACE include those with new ischemic changes on the ECG, troponin-confirmed acute myocardial injury, new-onset left ventricular systolic dysfunction (ejection fraction < 40%), newly diagnosed moderate-severe ischemia on stress imaging, and/or a high risk score on CDP. 4, 13, 14 5] [6] [7] In the patients with a negative initial evaluation, ICA is also indicated for those categorized as high risk on a validated risk stratification instrument.

10] [11] Recommendation-Specific Supportive Text provides a comprehensive assessment of the extent and severity of obstructive CAD. Moreover, the determination of the severity of anatomic CAD is critical to guide the use of coronary revascularization. 6 . Approximately 6% to 15% of troponin-positive ACS occurs in the absence of obstructive CAD. 17, 18 Additional testing may be helpful to identify the cause that may alter an ensuing therapeutic strategy. 19 Evidence supports that CMR can identify wall motion abnormalities and myocardial edema and distinguish infarct-related scar from non-CAD causes such as myocarditis and nonischemic cardiomyopathy. When performed within 2 weeks of ACS, CMR can be useful to identify MI with nonobstructive CAD (MINOCA) from other causes.

There are many potential causes of acute chest pain in the months after CABG. Musculoskeletal pain from sternotomy remains the most common. However, other

causes such as myocardial ischemia from acute graft stenosis or occlusion, 1,2 pericarditis, PE, sternal wound infection, or nonunion should also be considered. Poststernotomy pain syndrome is defined as discomfort after thoracic surgery, persisting for at least 2 months, and without apparent cause. 15 The incidence of post-sternotomy pain syndrome has been found to be as low as 7% and as high as 66%, [16] [17] [18] [19] with a higher prevalence in women compared with men within the first 3 months of thoracic surgery (51.4% versus 31.3%; P < 0.01) but, after 3 months, postoperative sex difference in prevalence was not seen. 20 Graft failure within the first year post-CABG using saphenous venous grafts is usually a result of technical issues, intimal hyperplasia, or thrombosis. 5 nternal mammary artery graft failure within the first-year post-CABG is most commonly attributable to issues with the anastomotic site of the graft.

Reasons for acute chest pain several years after CABG include either graft stenosis or occlusion or progression of disease in a non-bypassed vessel. One year after CABG, ∼10% to 20% of saphenous vein grafts fail, while by 10 years, only about half of saphenous vein grafts are patent. 5 In contrast, the internal mammary artery has patency rates of 90% to 95% 10 to 15 years after CABG. 6 Compared with the use of saphenous vein grafts, the use of radial artery grafts for CABG also resulted in a higher rate of patency at 5 years of follow-up. 7 In addition, knowledge of the native coronary anatomy and type of revascularization (complete or incomplete) is useful for interpretation of functional testing.

Abstract

Circulation is available at www.ahajournals.org/journal/circ *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. †ACC/AHA Representative. ‡ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison. §Society of Cardiovascular Computed Tomography Representative. ‖Lay Patient Representative. ¶Society for Academic Emergency Medicine Representative. #Former ACC/AHA Joint Committee member; current member during the writing effort. **Society for Cardiovascular Magnetic Resonance Representative. † †American College of Chest Physicians Representative. ‡ ‡American Society of Echocardiography Representative. § §Task Force on Performance Measures, Liaison.

Used. For patients presenting with acute or stable chest pain, risk for coronary artery disease and adverse events should be estimated using evidence-based diagnostic protocols. Figure 1 illustrates the take-home messages.

PREAMBLE

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cardiovascular care. The ACC and AHA sponsor the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. For some guidelines, the ACC and AHA partner with other organizations.

Intended Use

Clinical practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice

in the United States, but these guidelines are relevant to patients throughout the world. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients' interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment.

Clinical Implementation

Management, in accordance with guideline recommendations, is effective only when followed by both practitioners and patients. Adherence to recommendations can be enhanced by shared decision-making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities.

Methodology and Modernization

Relationships With Industry and Other Entities

The ACC and AHA have rigorous policies and methods to ensure that documents are developed without bias or improper influence. The complete policy on relationships with industry and other entities (RWI) can be found online. Appendix 1 of the guideline lists writing committee members' relevant RWI; for the purposes of full transparency, their comprehensive disclosure information is available in the Supplemental Appendix. Comprehensive disclosure information for the Joint Committee is also available online.

An independent evidence review committee is commissioned when there are ≥1 questions deemed of utmost clinical importance and merit formal systematic review to determine which patients are most likely to benefit from a drug, device, or treatment strategy, and to what degree. Criteria for commissioning an evidence review committee and formal systematic review include absence of a current authoritative systematic review, feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline, relevance to a substantial number of patients, and likelihood that the findings can be translated into actionable recommendations. Evidence review committee members may include methodologists, epidemiologists, clinicians, and biostatisticians. Recommendations developed by the writing committee on the basis of the systematic review are marked " SR . "

department (ED) in the United States and accounts for > 6.5 million visits, which is 4.7% of all ED visits. 1 Chest pain also leads to nearly 4 million outpatient visits annually in the United States. 2 Chest pain remains a diagnostic challenge in the ED and outpatient setting and requires thorough clinical evaluation. Although the cause of chest pain is often noncardiac, coronary artery disease (CAD) affects > 18.2 million adults in the United States and remains the leading cause of death for men and women, accounting for > 365 000 deaths annually. 3 Distinguishing between serious and benign causes of chest pain is imperative. The lifetime prevalence of chest pain in the United States is 20% to 40%, 4 and women experience this symptom more often than men. 5 Of all ED patients with chest pain, only 5.1% will have an acute coronary syndrome (ACS), and more than half will ultimately be found to have a noncardiac cause. 6 Nonetheless, chest pain is the most common symptom of CAD in both men and women.

Chest pain is one of the most common reasons that people seek medical care. The term "chest pain" is used by patients and applied by clinicians to describe the many unpleasant or uncomfortable sensations in the anterior chest that prompt concern for a cardiac problem. Chest pain should be considered acute when it is new onset or involves a change in pattern, intensity, or duration compared with previous episodes in a patient with recurrent symptoms. Chest pain should be considered stable when symptoms are chronic and associated with consistent precipitants such as exertion or emotional stress.

[3] [4] [5] [6] [7] Synopsis

Most patients who present to the ED with chest pain are women, particularly among those ≥65 years of age. 8 The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial demonstrated that women with moderate-to-severe ischemia are more symptomatic than men. 9 Women are less likely to have timely and appropriate care. 10 This could be explained by the fact that women are more likely to experience prodromal symptoms when they seek medical care. 11 16 Recommendation-Specific Supportive Text

Precipitating factors

Physical exercise or emotional stress are common triggers of anginal symptoms.

Occurrence at rest or with minimal exertion associated with anginal symptoms usually indicates ACS.

Positional chest pain is usually nonischemic (eg, musculoskeletal).

Relieving factors

Relief with nitroglycerin is not necessarily diagnostic of myocardial ischemia and should not be used as a diagnostic criterion.

discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% of women versus 54.8% of men; P < 0.001). 3 Similar results were found in the YOUNG-MI (Myocardial Infarction) registry where young men and women (≤50 years of age) were equally likely to present with chest pain, although women were more likely to also have other associated symptoms. 7 The HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke) study used cardiolinguistic machine learning to record patient-reported symptoms and, in those diagnosed with obstructive CAD, there was no sex difference in the occurrence of chest pain. 6 In a prospective trial of 1941 patients (39% women) with suspected ACS examining the diagnostic value of high-sensitivity cardiac troponin (cTn), chest pain was reported in 92% of women and 91% of men. 5 Additionally, women with acute myocardial infarction (AMI) were more likely to present with "typical" symptoms than men (77% versus 59%; P=0.007).

Recommendation-Specific Supportive Text presenting with suspected ACS in whom English may not be their primary language, adequately addressing language barriers with the use of language translation is vital to obtain an accurate and complete history. Formal translation services such as those provided through institutions and virtual translation are recommended.

2.1.4. Patient-Centric Considerations

Although chest pain remains one of the most common reasons that patients seek evaluation, among both sexes, there is a tendency for some patients to minimize perceived risk for cardiac disease, resulting in potentially avoidable delays in care. 1 To alleviate this problem, efforts should be made to educate all people regarding their risk for a cardiac event and educate patients about the need for timely care if a heart attack is suspected. Education is essential regarding the need to call 9-1-1, provide transportation by EMS to the nearest ED, initiate early assessment and management of suspected ACS, including transmittal of prehospital ECGs, 2 and intervene if complications occur en route to the ED. 3 The ACC's Early Heart Attack Care guide is a resource to help educate the public about early recognition of potential cardiac symptoms and the importance of activating 9-1-1 for transportation. 4, 5 commendation-Specific Supportive Text 1. To ensure the timely delivery of appropriate care, especially reperfusion therapy, it is strongly recommended that patients with acute chest pain be transported to the ED by trained EMS personnel. 2, 3 MS transportation is associated with substantial reductions in ischemic time and treatment delays. Moreover, 1 in 300 patients with chest pain transported to the ED by private vehicle suffers a cardiac arrest en route. 3 Understanding the mode of transportation to the ED for patients with chest pain and educating those who arrive by private vehicle on the associated dangers is an important aspect of management.

2.2. Physical Examination

Synopsis

Life-threatening causes of chest pain include, but are not limited to, ACS, PE, aortic dissection, and esophageal rupture. Because ST-segment-elevation myocardial infarction (STEMI) can be recognized on the ECG, the major challenge is to distinguish between non-STsegment-elevation (NSTE)-ACS and noncardiac chest pain. 1 With an uncomplicated AMI, the examination may be negative. Sudden onset of severe chest pain or back pain associated with limb pulse differential suggest aortic dissection, 2 but sensitivity of the latter finding alone was only 30%. Recommendation-Specific Supportive Text

that are life-threatening, such as ACS, PE, aortic dissection, and esophageal rupture, to facilitate rapid implementation of appropriate treatment. 1 pecific clues can be helpful (Table 4 ). Chest tenderness on palpation or pain with inspiration markedly reduce the probability of ACS. 1, 5, 6 ntegrating the examination with other elements of the evaluation is crucial to establishing the correct diagnosis.

2.3. Diagnostic Testing

2.3.1. Setting Considerations

Recommendations for Setting Considerations Referenced studies that support the recommendations are summarized in Online Data Supplement 5.

1. Unless a noncardiac cause is evident, an ECG should be performed for patients seen in the office setting with stable chest pain; if an ECG is unavailable the patient should be referred to the ED so one can be obtained.

The goals in patients presenting to the ED or office with acute chest pain are: 1) identify life-threatening causes; 2) determine clinical stability; and 3) assess need for hospitalization versus safety of outpatient evaluation and management. These concerns entail consideration of the full extent of clinical data. The ACC/AHA STEMI and NSTE-ACS guidelines categorize chest pain cause into 4 types: STEMI, NSTE-ACS, stable angina, and noncardiac. 6, 7 The 12-lead ECG, which should be acquired and interpreted within 10 minutes of arrival to a medical facility [1] [2] [3] [4] [5] [6] [7] 11 (Section 2.3.2, EC ), is pivotal in the evaluation because of its capacity to identify and triage patients with STEMI to urgent coronary reperfusion. Other ST-T abnormalities consistent with possible ischemia also mandate prompt evaluation in a hospital setting. In both cases, transfer should be by EMS; personal automobile for this purpose is associated with increased risk and should be avoided. [3] [4] [5] Patients with stable angina or noncardiac chest pain that is not life-threatening should be managed as outpatients.

1. The ECG is central to the evaluation of stable angina in the office setting to ensure that ACS Aortic dissection Connective tissue disorders (eg, Marfan syndrome), extremity pulse differential (30% of patients, type A > B) 8 Severe pain, abrupt onset + pulse differential + widened mediastinum on CXR > 80% probability of dissection 9 Frequency of syncope > 10%

is not missed. 1, 2, 6, 7 If an ECG cannot be obtained, transfer to the ED should be initiated. 2. Transfer by EMS from the office setting for acute chest pain with suspected ACS or other life-threating conditions is recommended because of the important advantages provided by EMS including: 1) acquisition of a prehospital ECG, which can facilitate reperfusion if ST elevation is present; 2) presence of trained personnel who can provide treatment for chest pain, arrhythmias, and implement defibrillation en route; and 3) shorter travel time to the ED. 1-7,10 ] 6, 7 Therefore, regardless of the setting, an ECG should be obtained and interpreted within 10 minutes of arrival. If this cannot be achieved in the office setting, immediate transfer to the ED by EMS is recommended. ] 6, 7 This results in an important and avoidable delay in readiness of the ED and reperfusion teams to implement optimally timed reperfusion therapy.

Chest radiographs are rapid, noninvasive tests that can be used to screen for several disorders that may present with chest pain. The yield of chest radiography depends on the pretest probability and will thus be higher when history or physical examination point to a greater likelihood of a given diagnosis. However, chest radiographs often do not lead to a diagnosis that requires intervention, 1 and their use should be guided by clinical suspicion.

1 C-EO

3. Clinicians should be familiar with the analytical performance and the 99th percentile upper reference limit that defines myocardial injury for the cTn assay used at their institution.

Cardiovascular biomarkers can be useful for the diagnostic and prognostic assessment of patients with chest pain. Their most important application in clinical practice is for the rapid identification or exclusion of myocardial injury. The preferred biomarker to detect or exclude myocardial injury is cTn (I or T) because of its high sensitivity and specificity for myocardial tissue. 33 hs-c n is preferred and can detect circulating cTn in the blood of most "healthy" individuals, with different sex-specific thresholds. 17, 21, 34 cTn is organspecific but not disease-specific. Numerous ischemic, noncoronary cardiac, and noncardiac causes of cardiomyocyte injury can result in elevated cTn concentrations. 17, 21, 24, 25 Therefore, interpretation of cTn results requires integration with all clinical information. 17, 21 Although multiple other cardiovascular biomarkers, including some in common clinical use such as natriuretic peptides, have been shown to be associated with the risk of adverse cardiovascular outcomes in patients with chest pain, none have sufficient diagnostic accuracy for myocardial injury to be recommended for that purpose. The use f D-dimer for diagnosis of PE is discussed in Section 4.2.2.

1. The preferred biomarker to detect or exclude cardiac injury is cTn (I or T) because of its high sensitivity and specificity for myocardial tissue. Det 1] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] A cTn concentration > 99th percentile upper reference limit, which is assay-dependent, is an indicator of myocardial injury. 1, 9, 21 The coefficient of variation at the 99th percentile upper reference limit for each assay should be ≤10%. 8,21 2. There is ample evidence for the superiority of hs-cTn assays over conventional cTn assays in multiple aspects of evaluation for patients presenting with chest pain with and without AMI. 17, 21, 24, 25, 33 he sensitivity and negative predictive values are greater with hs-cTn compared with previous generation assays. 17, 21, 24, 25 In addition, the time interval from onset of chest pain to a detectable concentration at patient presentation is shorter with hs-cTn, affording more rapid rule-in and rule-out algorithms. 22 Although it is sometimes challenging to diagnostically discriminate among these causes of myocardial injury, irrespective of the final diagnosis, the presence of myocardial injury is associated with a higher risk of adverse outcomes among patients with chest pain. 35 . The level of detection, 99th percentile upper reference limit, analytical precision, and criteria for a significant delta are assay-specific, including among the many different manufacturers of the same analyte (eg, hs-cTnI). To appropriately apply a cTn assay, clinicians must be familiar with these analytical performance properties for the assay(s) that they use in their practice. 21 8] [29] [30] [31] [32] The addition of CK-MB or myoglobin to cTn for evaluation of patients presenting with chest pain is not beneficial.

After ACS has been ruled out, stress echocardiography can be used to define ischemia severity and for risk stratification purposes. For TTE and stress echocardiography, ultrasound-enhancing agents are helpful for left ventricular opacification when ≥2 contiguous segments or a coronary territory is poorly visualized. 3 5] [6] Contraindications to stress type (exercise versus pharmacologic) and stress echocardiography are reported in Table 5 .

This guideline focuses on elective and urgent cardiac testing and, in both circumstances, imaging using ionizing radiation during pregnancy or postpartum while breast feeding should generally be avoided. When imaging is necessary to guide management, the risks and benefits of invasive angiography, SPECT, PET, or CCTA should be discussed with the patient. In all cases for a test deemed clinically necessary, the lowest effective dose of ionizing radiation should be used, including considerations for tests with no radiation exposure (eg, echocardiography, CMR imaging). 1 Radiation risk to the fetus is very small. Iodinated contrast enters the fetal circulation through the placenta and should be used with caution in a pregnant woman. 3] [4] [5] If contrast is needed for a postpartum woman, breastfeeding may continue because < 1% of iodinated contrast is excreted into the breast milk and absorbed into the infant's gastrointestinal tract. 6

The initial assessment of patients presenting with acute chest pain is focused on the rapid identification of patients with immediately life-threatening conditions such that appropriate medical interventions can be initiated. Included among the potentially life-threatening

(emergency) causes of chest pain are ACS (Section 4.1), acute aortic syndromes (Section 4.2.1), and PE (Section 4.2.2). Myopericarditis is heterogeneous in its manifestations but can include fulminant myocarditis, which carries a high mortality rate (Section 4.2.3). A subset of noncardiovascular syndromes are also immediately life-threatening, including esophageal rupture (Section 4.3.1), tension pneumothorax, and sickle cell chest crisis. Nonemergency causes of chest pain, such as costochondritis and other musculoskeletal, or gastrointestinal causes, are discussed in Section 4.3. Such nonemergency causes predominate among patients presenting with acute chest pain; therefore, strategies that incorporate routine, liberal use of testing carry the potential for adverse effects of unnecessary investigations and unnecessary cost. Figure 7 provides an overview of this approach. [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] *Screening for potential pregnancy by history and/or pregnancy testing should be performed according to the local imaging facilities policies for undertaking radiological examinations that involve ionizing radiation in women of child-bearing age.

†Low-dose dobutamine may be useful for assessing for low-gradient AS.

51 4. Previous test results should always be considered in the evaluation of patients with acute chest pain once ACS has been ruled out. In those with recent cardiac testing and normal findings who do not have biomarker evidence of acute myocardial injury, further testing is of limited value, provided that adequate exercise levels were achieved or pharmacologic stress was performed, imaging was of sufficient quality, and there are no changes in symptom frequency or stability at the new visit. The "warranty" intervals (Table 7 ) for the various cardiac testing modalities differ because of the low number of incident events among patients with a normal CCTA, although patients with normal stress testing may still have significant plaque and a higher event rate. [20] [21] [22] The warranty period for a normal stress-rest SPECT is highly variable because it is primarily determined by the type of stress, the patient's clinical characteristics, and left ventricular ejection fraction. 52 5. To use cTn properly, an understanding of the assay used (high sensitivity or conventional) and the timing of chest pain onset relative to ED arrival is critical. 17, 38, 39 CDPs that emphasize rapid rule-out based on single hs-cTn concentrations below the limit of detection should be limited to patients whose symptoms started at least 3 hours before ED arri val. 2, 5, 6, 11, 14, 16, 25, [40] [41] [42] [43] [53] [54] [55] Unlike high-sensitivity assays, clinical decision-making based on single measurement of conventional cTn has not been validated. 36 If the clinical presentation is still suspicious for ACS or diagnostic uncertainty remains after serial cTn measurement, it may be reasonable to repeat cTn assay later (ie, beyond 3 hours for high-sensitivity and beyond 6 hours for conventional assays).

≤1%. 17 This estimate is based on clinical information that is readily available during the course of evaluation, typically occurring in the ED. There are several methods to determine that a patient is low risk (Table 8 ) but, invariably, all involve taking an appropriate history and physical examination, demonstration that the ECG is normal, nonischemic, or unchanged from the previous ECG, and cTn measurement at a single point in time (if presentation is > 3 hours from symptom onset and using a high-sensitivity assay) or serially [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] (with incorporation of a chest pain risk score into the CDP if using a conventional cTn assay). Importantly, there is no evidence to support routine admission or cardiac testing for chest pain patients who are low risk, although outpatient CAC scanning can provide additional information for longer-term risk stratification.

1. Acute chest pain in patients with prior CABG may be caused by myocardial ischemia as a result of technical errors at the graft anastomotic site, thrombosis within the graft, graft intimal hyperplasia, or vasospasm within arterial grafts. Progressive atherosclerosis within bypass grafts or the native coronary vessels may also result in acute chest pain caused by myocardial ischemia. Noninvasive stress imaging testing is reasonable in these patients as stress imaging will identify ischemic myocardial territories that will further guide revascularization for patients who are amenable to and are candidates for revascularization. CCTA has a great degree of accuracy with a sensitivity and specificity of detecting complete graft occlusions, 99% and 99%, respectively, when compared with the standard of ICA. 21 Furthermore, CCTA was ideal in assessing bypass grafts because of the large size of these vessels, decreased vessel calcification, and decreased motion of these vessels when compared with native coronary vessels. Evaluation of bypass grafts has been shown to be successful in 93% to 100% of patients. 21 In patients who have acute chest pain without features of ACS, CCTA is especially useful for assessing graft patency and is less robust for assessing native coronary vessel stenosis in this population.

In 2015, there were nearly 500 000 people in the United States who received maintenance dialysis to treat endstage renal disease. 1 Chest pain occurs during hemodialysis in 2% to 5% of patients. 6, 7 Causes are numerous and

related to the high prevalence of severe cardiovascular disease in this population and the dialysis procedure itself. Causes include AMI or ACS, pericarditis, PE, pleuritis, hemolysis, gastroesophageal reflux, subclavian steal, and musculoskeletal disorders. 7 Myocardial ischemia is the most frequent serious cause and can be induced by hypotension 6, 7 or tachyarrhythmias 2 occurring during dialysis in patients with CAD. AMI in patients undergoing dialysis is less frequently associated with chest pain than in patients who are not on dialysis, but warning signs may include diaphoresis or dyspnea. 3 Unusual but serious causes of chest pain during dialysis are embolism 6 and vessel perforation by catheter. 4, 5 When indicated, cardiac testing for patients on dialysis should be the same as those who are not on dialysis.

COR LOE Recommendation 2a B-NR

1. [3]

The most frequent presenting complaint of cocaine abuse is acute chest pain, resulting from ≥1 of the alkaloid's many cardiovascular actions. 1, 4, 5 Cocaine produces a hyperadrenergic state by blocking neuronal reuptake of norepinephrine and dopamine. The accumulation of these catecholamines increases heart rate and blood pressure, sometimes dramatically. These actions and the drug's simultaneous effect of coronary vasoconstriction and elevated myocardial oxygen demand can produce myocardial ischemia and even infarction in the absence of obstructive CAD. [6] Methamphetamine has also been shown to lead to myocardial ischemia from mechanisms similar to cocaine. Studies have shown that methamphetamine can result in decreased myocardial perfusion. Like cocaine, methamphetamine also may reduce coronary sinus blood flow. 7 It has been reported that up to 70% of methamphetamine users have an abnormal ECG, with the most common finding being tachycardia. 8 Additional abnormalities on the ECG have been attributed to presence of hypertension, pulmonary artery hypertension, and cardiomyopathy, all of which have been associated with methamphetamine use. 9 General principles for risk stratification of patients with chest pain apply to patients with cocaine or methamphetamine use. 4 Recommendation-Specific Supportive Text

2] [3] For low-risk patients, decision aids can facilitate risk communication between the clinician and the patient and increase patients' understanding of their risk and the

importance of outpatient follow-up after discharge from the ED. For intermediate-risk patients, admission to an observation unit or discharge from the ED with further, timely evaluation in an outpatient setting is acceptable. Decision aids such as Chest Pain Choice can effectively facilitate shared decision-making regarding the need for admission, observation, or discharge for further evaluation in an outpatient setting. 3 commendation-Specific Supportive Text 1. Adult ED patients with acute chest pain who are deemed low risk are frequently admitted for observation and cardiac stress testing or CCTA, resulting in increased cost to the patient and the health care system. 2 Shared decision-making is the process by which patients and clinicians share information and take steps to build consensus about preferred tests and treatments. In shared decision-making, both parties share information: the clinician offers options and describes the potential harms and benefits, and the patient communicates his or her preferences. Patients are prepared with a better understanding of the relevant factors influencing the decision and share responsibility for deciding how to proceed. Shared decision-making rests on the principles of patient centered care, including respect for patient autonomy (ie, that a patient's informed preferences should be the basis for medical action). 4 Decision aids are patient-centered tools designed to facilitate shared decision-making between a patient and the clinician such that patients' values and preferences are incorporated into health care decisions. 5 Shared decision-making, however, can be performed without a decision aid; lack of a decision aid should not preclude attempts at shared decision-making. 2. In a single-center randomized trial of adults presenting to the ED with a chief complaint of chest pain (n=204) who were being considered by the treating clinician for admission to the observation unit for cardiac stress testing, patients randomized to shared decision-making facilitated by the Chest Pain Choice Decision Aid 2,3 had greater knowledge, were more engaged in the decision-making process, and less frequently decided to be admitted to the observation unit for stress testing (58% versus 77%, absolute difference 19%, 95% CI: 6%-31%). 2 There were no MACE after discharge in either group. The decision aid was subsequently tested in a population of 898 patients with greater socioeconomic diversity recruited from 6 EDs across the United States.

Alternative nonischemic causes for acute chest pain should be considered if an ischemic cause is not suspected based on initial evaluation. Echocardiography, as a portable bedside noninvasive and almost universally available tool, should be used to unmask some imminently dangerous but potentially treatable cardiac conditions. TTE is the primary tool to diagnose pericardial effusions with and without tamponade, aortic dissections (TTE and transesophageal echocardiography [TEE]), acute right ventricular dysfunction in the setting of PE, as well as mechanical complications of MI (ventricular septal rupture, free wall rupture, papillary muscle dysfunction and rupture).

Echocardiography can also identify cardiac masses, emboli, or clots in transit, intracardiac shunting, or endocarditis. Furthermore, beyond the anatomic findings, echocardiography can be used to noninvasively assess volume status, pulmonary hypertension, valvular stenosis, and regurgitation. Many of these entities may present with acute chest pain as well as shortness of breath.

2] [3] [4] [5] [6] Rapid echocardiographic assessment may facilitate imaging of the patient while symptomatic.

4.2.1. Acute Chest Pain With Suspected Acute Aortic Syndrome

Recommendations

Acute aortic syndrome describes diseases involving disruptions in the aortic wall, including aortic dissection, intramural hematoma, and penetrating aortic ulcer. 1 The annual incidence is 2 to 4 cases/100 000, with higher prevalence with genetic conditions that weaken the aortic wall. 2 Prominent risk factors include hypertension atherosclerosis and connective tissue disease. Cocaine use may provoke dissection even without other risk factors.

Acute onset of severe chest or back pain heralds acute aortic dissection in 80% to 90% of patients, sometimes characterized as ripping or tearing. 3 Progression can produce end-organ hypoperfusion, and proximal extension may cause tamponade, severe acute aortic regurgitation, or rarely, STEMI. Intramural hematomas, which differ from dissection by absence of an identifiable intimal flap, have a lesser understood natural history but are typically evaluated and treated in a similar manner to dissections.

Recommendation-Specific Supportive Text

The incidence of PE is estimated at 65 cases per 100 000, but some cases are asymptomatic and others undiagnosed. 5, 6 One-third of deaths are sudden, and 60% are undiagnosed before death. 7 Risk factors for PE are the same for venous thromboembolism and include inherited hypercoagulable states and acquired risk factors (recent surgery, trauma, immobilization, malignancy, smoking, obesity, oral contraception). Recognition of PE can be challenging because symptoms and clinical signs may be nonspecific. Dyspnea followed by chest pain, classically pleuritic, is the most common presenting symptom. 1 Signs of deep venous thrombosis may be present on examination. 5 commendation-Specific Supportive Text 1. CTA using PE protocol is the diagnostic modality of choice in stable patients; ventilation-perfusion scanning is a second-line alternative in the acute setting. 3, 4 Use of clinical prediction rules to select patients for imaging can decrease radiation exposure and cost. 8 Troponin (and brain natriuretic peptide) can be elevated, and echocardiography may reveal acute right ventricular strain consequent to large PEs; troponin and brain natriuretic peptide are both markers for higher mortality rate. 2 2. Recognition of PE is important because prompt anticoagulation improves outcomes. 2 Clinical assessment combined with pretest risk stratification can help select patients appropriate for diagnostic imaging. In the absence of shock, diagnostic evaluation depends on the clinical assessment of pretest probability. 3 Several prediction rules are available that add predictive value to clinical assessment. 4

Pericarditis and myocarditis share overlapping common causes and likely form a continuum. 8 In patients with pericarditis, a minimally elevated troponin does not appear to confer a worse prognosis. 14 Most cases of pericarditis in developed nations are viral, although tuberculosis is sometimes a consideration.

Pericarditis classically presents with chest pain that is sharp, pleuritic, and which may be improved by sitting up or leaning forward, although in many instances such findings are not present. A pericardial friction rub may be audible. Widespread ST-elevation with PR depression is the electrocardiographic hallmark, although changes are nonspecific and may be transient.

Clinical manifestations of myocarditis are varied and include chest pain that is often sharp and reflective of epicardial inflammation involving the pericardium. Myocardial dysfunction often causes fatigue and exercise intolerance, and predominance of heart failure distinguishes myocarditis from pericarditis. Troponin is usually elevated. 15 commendation-Specific Supportive Text or if there is diagnostic uncertainty, CMR is useful to determine myocardial edema, thickening, and late enhancement. CMR may also show evidence of pericardial effusions. 2, 16 ] [9] [10] CMR features that are suggestive of acute pericarditis include enhancement or thickened pericardium, although such findings can also be seen in the presence of pericardial fibrosis. In addition, increased signal on T2-weighted images correlates with edema, which may be seen in acute myopericarditis. The presence of pericardial adhesions between the visceral and parietal pericardium may be useful in patients with suspected acute pericarditis or pericardial constriction. 7-10 3. In patients with suspected myopericarditis, echocardiography may show segmental left ventricular wall hypokinesis, which suggests myocardial involvement in patients with myocarditis and is, therefore, a useful tool in these patients. Patients with acute pericarditis may also have echocardiographic findings such as increased pericardial brightness or pericardial effusion with or without tamponade physiology. Some patients with acute pericarditis may also have normal echocardiographic findings. 9,17 4. In patients with suspected acute pericarditis, cardiac CT with or without contrast may show features that are suggestive of acute pericarditis, such as pericardial thickening or enhancement (after contrast administration). Additionally, CT attenuation values of pericardial effusion can help distinguish between exudative and transudative pericardial fluid. There are limited data on the accuracy of cardiac CT in diagnosing acute pericarditis; a small study showed that pericardial thickening or enhancement was the most accurate single parameter for pericarditis, with sensitivity of 54% to 59% and specificity of 91% to 96%. Therefore, cardiac CT is a reasonable second-line study in these patients.

Chest pain may occur in the presence of VHD, particularly stenotic VHD such as aortic valve stenosis and mitral valve stenosis with secondary pulmonary hypertension. Chest pain may also occur after papillary muscle rupture in the setting of MI or in acute degenerative mitral valve disease after spontaneous chordal rupture. Chest pain may also occur in the setting of acute severe aortic insufficiency, which may be related to acute aortic pathology such as an aortic dissection manifesting as severe acute chest pain that may radiate to the back. The cause of chest pain in patients with aortic valve stenosis may be secondary to coexisting obstructive epicardial CAD 1 or, more commonly, chest pain may occur as a result of coronary microvascular dysfunction 2 in the presence of very elevated left ventricular pressure caused by a high left ventricular afterload, along with the associated left ventricular hypertrophy. The cause of chest pain in patients with severe mitral

valve stenosis is more likely to be secondary to epicardial obstructive CAD 1 although, less likely, chest pain may occur in isolated mitral valve stenosis resulting from low cardiac output and decreased coronary perfusion. 1 commendation-Specific Supportive Text 1. Patients with VHD may present with chest pain particularly in the setting of stenotic VHD, severe valvular regurgitation in the setting of AMI with ruptured papillary muscle resulting in acute severe mitral valve insufficiency, or acute aortic valve insufficiency in the setting of acute aortic pathology, such as aortic dissection. 3, 4 TTE is useful in assessing valvular pathologies because it is widely available and is therefore a good first-line test in these patients to determine the presence, severity, and cause of VHD. 3

2. The ability to attain adequate 3-dimensional (3D)

transthoracic images depends on the ability to obtain adequate 2-dimensional images. 5 In these clinical situations where TTE images are technically inadequate, TEE with 3D images, if required, is useful to determine the severity and cause of VHD. 3,6 3. There may be clinical situations when TTE and TEE may not be technically adequate to assess the severity and cause of VHD. In such circumstances, CMR may be useful to objectively assess the severity and cause of VHD. 6 The aorta can also be visualized on CMR and can therefore be used to assess acute aortic pathologies accompanying aortic valve insufficiency such as aortic dissection.

Among outpatients who present with chest pain, approximately 10% to 20% have a gastrointestinal cause. 1 Gastrointestinal pain may result from stimulation of chemoreceptors by acid or hyperosmolar substances, of mechanoreceptors by abnormal contraction or distention, or of thermoreceptors. 2 Some patients have abnormal perceptions of otherwise normal stimuli. Gastroesophageal reflux disease is the most likely cause for recurring unexplained chest pain of esophageal origin. 3 Chest pain caused by gastroesophageal reflux disease can mimic myocardial ischemia and may be described as squeezing or burning. The duration can be minutes to hours, often occurs after meals or at night, and can worsen with stress. Depending on the severity, it may or may not resolve spontaneously or with antacids. Esophagitis not related to reflux may be caused by medications, underlying infections such as candidiasis, or radiation injury. Allergic conditions are associated with eosinophilic esophagitis, which is diagnosed by biopsy. Esophageal motility disorders such as achalasia, distal esophageal spasm, and nutcracker esophagus are less common but can present as squeezing retrosternal pain or spasm, often accompanied by dysphagia.

1. The first step in evaluation of potential esophageal chest pain is a careful history. Although the clinical presentation often does not provide adequate clues to distinguish cardiac from esophageal pain, some symptoms may be suggestive of an esophageal cause, such as heartburn, regurgitation, or dysphagia, and relief with antacid or antisecretory agents. These symptoms, however, are not sufficiently specific to be fully diagnostic. A history of use of medications such as nonsteroidal anti-inflammatory agents, potassium supplements, iron, or bisphosphonates should be sought. Physical examination is often unrevealing. When an esophageal cause of chest pain is suspected, upper endoscopy should be considered. 4 Symptoms and signs that merit early evaluation (usually within 2 weeks) include dysphagia, odynophagia, gastrointestinal bleeding, unexplained iron deficiency anemia, weight loss, and recurrent vomiting. Patients without these symptoms may merit a trial of empiric acid suppression therapy. 5 If an upper endoscopy is normal and the symptoms persist despite a trial of acid suppression, consideration should be given to additional evaluation, such as esophageal function testing and pH monitoring, to exclude other esophageal causes. 6

4.3.2. Evaluation of Acute Chest Pain With Suspected Anxiety and Other Psychosomatic Considerations

Recommendation for Evaluation of Acute Chest Pain With Suspected Anxiety and Other Psychosomatic Considerations Referenced studies that support the recommendation are summarized in Online Data Supplement 25.

COR LOE Recommendation

2a B-R

1. 3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

Although the heart-brain relationship is well established, [15] [16] [17] its clinical relevance has been enhanced by recognition of stress cardiomyopathy. 18, 19 ] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Chest pain in these patients has been variously labeled angina, angina-like, "atypical" angina, or noncardiac chest pain based on its deviation from characteristic ischemic cardiac discomfort. 1] [22] [23] The close association of this symptom with psychological syndromes such as anxiety, panic attack, depression, somatoform disorder, and cardiophobia suggests that there may be a psychogenic origin in many patients. These factors have also raised consideration of mechanisms for noncardiac chest pain such as central nervous system-visceral interactions, low pain thresholds, hyperbody vigilance, sym-

4] [25] [26] [27] [28] [29] [30] It has been reported that these patients undergo extensive and repetitive cardiac testing and have low referral to cognitive-behavioral therapists, suggesting a lost opportunity for pharmacologic or cognitive-behavioral therapy. 6 commendation-Specific Supportive Text 1. Most low-risk patients presenting to the ED or office setting with chest pain do not have life-threatening conditions. ] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] It has been reported that in low-risk chest pain patients without evidence of cardiac disease, depression, anxiety, and gastroesophageal syndromes each exceeded CAD by almost 10-fold. 7 dditionally, care of these patients often includes multiple tests, high cost, and avoidable radiation exposure (5.0 mSv). 6 A low rate ( < 10%) of clinician inquiry, documentation, or referral has also been noted for psychological factors, even in chest pain patients with self-reported anxiety. 6, 7 A systematic review of therapy for patients with chest pain, no evidence of cardiac disease, and psychological disorders revealed that antidepressants and anxiolytics had mixed evidence for efficacy, 10 but a Cochrane database of psychotherapy (17 RCTs) for such patients revealed a 32% reduction in chest pain frequency 11 for a 3-month interval. Approaches using cognitive-behavioral methods were most effective. 11 These results were limited by small study cohorts and patient heterogeneity; however, they do suggest benefit from consideration of psychogenic factors in patients who continue to seek evaluation for chest pain despite previous definitive, negative workups.

4.3.3. Evaluation of Acute Chest Pain in Patients With Sickle Cell Disease

Recommendations for Evaluation of Acute Chest Pain in Patients With Sickle Cell Disease Referenced studies that support the recommendations are summarized in Online Data Supplement 26.

[5]

Acute chest syndrome is a leading cause of death for patients with sickle cell disease. 1, 2 Patients with sickle cell disease who are experiencing chest pain require prompt evaluation. 3 Although chest pain occurs in most, other manifestations of acute chest syndrome include shortness of breath, fever, arm and leg pain, and the presence of a new density on chest radiography. Older adolescents and adults with sickle cell disease who present with chest pain and shortness of breath should be evaluated for AMI or myocardial ischemia. 4 AMI occurs in patients with sickle cell disease at a relatively early age, usually without the traditional risk factors for ACS. Death from ACS in patients with sickle cell disease is significantly high in age-, sex-, and race-matched controls. 5 commendation-Specific Supportive Text

In patients with sickle cell disease who experience chest pain, ACS is associated with significant morbidity and mortality rates. These patients should be transferred to an acute care setting by EMS when there is clinical suspicion of ACS. 2. The recommended diagnostic evaluation for all adults with sickle cell disease who have a clinical presentation concerning for acute chest syndrome includes an ECG, troponin test, complete blood count with white blood cell differential, reticulocyte count, anteroposterior and lateral chest radiograph, and blood and sputum cultures.

5. EVALUATION OF PATIENTS WITH STABLE CHEST PAIN

as shown in Figure 11 . 2 This information can be obtained from performing a CAC scan or, when available, from a visual estimation of CAC based on prior noncardiac chest CT. Among the remaining patients classified as intermediate-high risk, selective testing may improve diagnosis of CAD and for risk stratification purposes.

Over the past several decades, patient presentation and observed obstructive CAD prevalence has changed, thus affecting patient selection for diagnostic testing. Current observations in the United States include:

• Typical exertional angina prevalence is generally low ( < 10%), with more patients presenting without the classic demand-related symptoms. 11 ymptoms can be infrequent (ie, on a weekly or monthly basis), 12, 13 which challenges the diagnostic evaluation. • Among patients undergoing a diagnostic evaluation, there is a relatively low prevalence of obstructive CAD and ischemia (ie, ∼10%). 11,14,15 ] [18] [19] • Current testing patterns result in a high normal coronary angiography rate (upward of 50%-60%). 20, 21 For the aforementioned reasons, use of a contemporary pretest probability estimates to define low-risk patients not requiring additional diagnostic testing is a primary goal of the initial evaluation of symptomatic patients with suspected CAD. 5 Even when contemporary pretest probability estimates are used, they have a low specificity for identifying patients with obstructive CAD. A CAC score of zero can be useful to identify patients with stable chest pain who are low risk, have a low likelihood of obstructive CAD, and a low risk of future

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 capacity 10 (Figure 12 ).

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 developed 4, 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

The approach to the diagnostic evaluation of patients with no known CAD who are at intermediate to high risk (Figure 12 ) should be guided by the ability to achieve highquality imaging as well as local availability and expertise. 8] [79] [80] CCTA is preferable in those < 65 years of age and not on optimal preventive therapies, while stress testing may be advantageous in those ≥65 years of age, because they have a higher likelihood

[81] [82] [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 CCTA 1, 84 or noninvasive stress testing. 34, 35 atient 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. ] [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.

8, 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. 17 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 0] [91] [92] [93] [94] [95] [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 8] [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 CMR 105 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 he 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.

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 2] [43] [44] [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 men 13, 41, 42, 44 ; such patients may benefit from additional testing (anatomic or stress testing).

5. Use of attenuation correction algorithms and prone

[48] [49] [50] [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 quential or Add-on Testing: What to Do if Index Test Results are Positive or Inconclusive 6. 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 70,94,109,110 9. After n 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] [21] [22] [23] 40, [73] [74] [75] [76] or CMR.

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 commendation-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.

used according to ACC/AHA clinical practice guidelines. 4,5

5.2.1. Patients With Obstructive CAD Who Present With Stable Chest Pain

Recommendations for Patients With Obstructive CAD Who Present With Stable Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplements 32 and 33.

Index Diagnostic Testing Anatomic Testing

1 A

1. [3] [4] 1 A

2. For patients with obstructive CAD who have stable chest pain despite optimal GDMT, those referred for ICA without prior stress testing benefit from FFR or instantaneous wave free ratio.

In patients with known CAD, physicians should opt to intensify GDMT first, if there is an opportunity to do so, and defer testing. In patients with a history of obstructive CAD, previous AMI, or previous coronary revascularization, assessing the severity of ischemia may be useful to guide clinical decision-making regarding the use of ICA and intensify preventive and anti-ischemic therapy.

Imaging should be considered in those with new onset or persistent stable chest pain (Figure 13 ). In patients with frequent angina or severe stress-induced ischemia, referral to ICA or CCTA is an option. 4 3] [4] 41 In the ISCHEMIA trial, a total of 5 179 patients with stable CAD and site-determined moderate-severe ischemia on stress testing were randomized to invasive versus conservative care strategies. 4 No difference in the composite primary MACE endpoint was observed at ∼3.3 years of follow-up. Patients presenting with daily, weekly, or monthly angina had a prompt and durable improvement in symptoms when randomized to invasive compared with conservative management. 41 . Coronary revascularization after identification of suspected lesion-specific ischemia (FFR ≤0.80 or instantaneous wave-free ratio ≤0.89) in obstructive CAD is associated with improved event-free survival compared with the use of PCI determined by anatomy alone. 3,5,6,42 3. In a patient presenting with new or recurrent chest pain symptoms, progression of CAD (ie, new or worsening stenosis or more extensive nonobstructive atherosclerotic plaque) may be characterized using CCTA. 43, 44 2] [53] [54] [55] CCTA-defined left main stenosis (nonobstructive and ≥50% stenosis) is associated with a high CAD event risk. 56, 57 Coronary revascularization confers a survival benefit among patients with left main CAD. 58 From randomized trials, major clinical outcomes in patients with left main CAD are similar with CABG and PCI at near-term follow-up of 1 to 2 years, although repeat revascularization rates are higher after PCI.

0] [61] [62] Diagnostic sensitivity and specificity of FFR-CT, compared with invasive FFR, is high ( > 90%). 32, 60 ress Testing 5. Observational findings reveal that patients with moderate-severe ischemia on PET and SPECT MPI have an improved outcome with early coronary

4] [65] Patients with moderatesevere ischemia on PET (≥10% ischemic myocardium) treated with PCI reported an improvement in angina when compared with those treated medically. 20 ] [16] [17] [18] Clinical trials of CMR have included subgroups with obstructive CAD, including 76% and 49% in the MR-IMPACT and MR-IMPACT2 studies, respectively, showing generally comparable diagnostic accuracy to stress SPECT MPI. 23, 24 Several large, multicenter registries reveal that stress CMR effectively risk stratifies patients with known CAD. [27] [28] [29] [30] In a multicenter registry of 2496 patients with a history of CAD, an abnormal stress CMR had a nearly 2-fold increased mortality hazard. 27 rom the SPINS Registry (Stress CMR Perfusion Imaging in the United States), patients with known CAD with MPI ischemia and scarring by late gadolinium enhancement had a relative hazard of 1.5 to 2.1 for CV death or nonfatal MI. 30 Prognosis worsens for patients by the extent and severity of inducible wall motion abnormalities on stress echocardiography. 66, 67 Recent randomized trial evidence supports the role of stress echocardiography to guide clinical decision-making. From the ORBITA (Objective Randomized Blinded Investigation With Optimal Medical Therapy in Stable Angina) trial, there was a greater reduction in the stress echocardiographic wall motion score among patients with single-vessel CAD treated with PCI compared with placebo (P < 0.0001). 68 In a secondary analysis, there was an interaction between the baseline stress echocardiographic wall motion score and the efficacy of PCI for improved angina at 6 weeks of follow-up. 69 That is, PCI-treated patients with a wall motion score ≥1 were more often angina-free compared with those in the placebo arm. 6. Evidence supports that the improved diagnostic accuracy of PET MPI is helpful in the patient with known CAD. In a randomized trial of 322 symptomatic patients with known CAD, the presence of low-and high-risk stress PET findings was associated with lower and higher rates of ICA when compared with SPECT MPI (P=0.001). 37 n this trial, nearly 1 in 5 patients with low-risk SPECT MPI findings underwent ICA, a rate more than twice that of stress PET MPI. Based on such evidence, PET is preferable over SPECT when both are available.

[40] Secondary Diagnostic Testing: For the Assessment of Vascular Territory Flow or Vessel-Specific Ischemia 8. Measurement of MBFR, when reduced, reflects abnormalities of flow within the epicardial coronary arteries and/or microvasculature and independently predicts risk of major CAD events. This can be effectively accomplished using PET 31, 70, 71 or CMR. 28 Normal MBFR may be helpful in excluding high risk anatomy, although reduced levels may provide a better estimate of disease extent and severity.

In patients with prior CABG who have stable chest pain, it is important to assess medical therapies and optimize all guideline-directed therapies. 1 2] [3] [4] [5] [6] [7] [8] [9] In those whose symptoms do improve after optimizing medical therapy, evaluation with stress testing can be useful to assess the degree of myocardial ischemia and determine which patients may benefit from coronary angiography. 6, 10 CTA can also be used to detect graft patency but is often less robust for assessing native coronary vessel ste-

10] [11] [12] [13] [14] [15] Recommendation-Specific Supportive Text Noninvasive stress imaging testing is reasonable in these patients to identify ischemic myocardial territories that will further guide revascularization for patients who are amenable to and are candidates for revascularization. 12] [13] [14] CCTA has a great degree of accuracy with a sensitivity and specificity of detecting complete graft occlusions, 99% and 99%, respectively, when compared with the standard of ICA. 20 urthermore, CCTA was ideal in assessing bypass grafts attributable to the large size of these vessels, decreased vessel calcification and decreased motion of these vessels when compared with native coronary vessels, with successful evaluation of bypass grafts in 93% to 100% of patients. 15

For patients with known nonobstructive CAD (luminal narrowing 1%-49%), CCTA can be useful for detection of new or worsening obstructive stenosis, atherosclerotic disease progression, and identification of high-risk plaque features, such as low attenuation plaque or positive remodeling 1,2,5-7,25 (Figure 13 ). 7] [28] [29] For this evaluation, the patient should be engaged in a process of shared decision-making before determining the final choice of the cardiac testing modality and in guiding the pathway for treatment decisions.

] [5] [6] From the PROMISE trial, nonobstructive CAD was associated with a 3-fold increase in MACE risk over ∼2 years of follow-up. 3 Additional analyses from the SCOT-HEART and PROMISE trials reveal that high-risk atherosclerotic plaque features are associated with an elevated MACE risk among patients with nonobstructive CAD. 4, 5 CCTA commonly identifies patients with nonobstructive CAD but can further define compositional alterations within the plaque (ie, noncalcified plaque) and positive remodeling. 4, 5, 7, 25, 30 These plaque features have been associated with inducible ischemia, identified as precursors for ACS, and independently predict MACE. 5, 6, 31 Recently, Williams et al reported that a low attenuation plaque burden was associated with a > 6-fold increase in incident MI for patients with nonobstructive CAD. 4 2. Controlled clinical trials reveal that FFR-CT improves diagnostic accuracy over and above obstructive CAD on CCTA when compared with invasive FFR. 12, 13 ] [10] [11] From the ADVANCE (Assessing Diagnostic Value of Noninvasive FFR-CT in Coronary Care) registry, FFR-CT changed treatment recommendations in two-thirds of patients, and there were no MACE at 90 days for patients with a negative FFR-CT. 10 From the SYNTAX 3 trial, 14

Signs and symptoms of ischemia occur because of focal obstructive CAD, but INOCA is common and may result from alterations in flow within the microvasculature. Thus, many symptomatic patients without obstructive CAD on previous workup may be candidates for assessment of coronary microvascular dysfunction and other causes of INOCA. 1 Patients at highest risk for coronary microvascular dysfunction include women, those with hypertension, diabetes, and other insulin-resistant states. 15 here is substantive evidence that testing focusing on documentation of coronary or microvascular flow abnormalities can aid in the diagnosis of microvascular angina, and abundant evidence supports that the addition of flow alterations improves risk stratification. Invasive coronary reactivity testing allows for the assessment of vasospasm, in addition to nonendothelial-dependent and endothelium-dependent microvascular reactivity. 2, 4 From the National Institutes of Health-NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation), impaired coronary flow reserve (ie, < 2.32) among women with no obstructive CAD was associated with an elevated hazard for major CAD events with lengthy follow-up of 10 years (P=0.03). 2 Among women with no obstructive

CAD, epicardial vasoconstriction was also significantly associated with higher rates of hospitalization for angina (P=0.0002). 2 Prognostic evidence is available supporting the novel contribution of PET MBFR techniques; several reports also note a benefit using CMR and echocardiographic techniques. A proposed diagnostic evaluation pathway is outlined in Figure 14 .

1. Evidence supports a role for invasive coronary reactivity testing, including prognostic evidence from the WISE study. 1, 2 The CorMicA (Coronary Microvascular Angina) trial enrolled symptomatic patients (74% women) without obstructive CAD and positive invasive coronary reactivity testing (n=76 patients to intervention and 75 to the blinded control group). The intervention consisted of anti-ischemic therapy using beta-blockers and angiotensin-converting enzyme inhibitors along with preventive care (statins) and lifestyle changes, including smoking cessation, and was associated with a significant improvement in angina and quality of life over 6 months (P=0.001). 4, 16 This small trial did not report any differences in 6-month MACE (P=0.8). 2. PET measurement of peak myocardial blood flow and MBFR, when reduced, reflects abnormalities

7] 17 PET measurement of MBFR improves risk stratification, including for patients with nonobstructive CAD, especially women, for whom coronary microvascular dysfunction is suspected. 18 . CMR has been used to evaluate MBFR. When validated against invasive coronary physiology measures, pixel-wise quantitative myocardial perfusion mapping by CMR was able to identify coronary microvascular dysfunction in a small study that included 23 patients with nonobstructive CAD. 19 The addition of coronary flow reserve improves prognostication.

5.3. Cost-Value Considerations in Diagnostic Testing

A general concept regarding cost is that layered testing (ie, when a test is followed by more tests) leads to higher costs. To minimize the potential needs for downstream testing, clinicians should select the test that is most likely to answer a particular question.

5.3.1. CCTA and CAC Scanning Cost-Value Considerations

In the outpatient setting, long-term costs were generally similar between CCTA and stress testing strategies. 1 Higher invasive angiography rates after CCTA are matched by a greater use of downstream stress testing after initial stress testing, resulting in minimal differences in cost at 2 to 3 years of follow-up. 1, 2 From the CON-SERVE (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization) trial, 823 patients were randomized to a selective versus direct referral strategy to ICA. Enrollment was limited to patients with nonemergent indications for ICA. 3 The selective referral arm included CCTA-guided use of ICA. Cumulative diagnostic costs were $1183 for the selective arm and $2755 for the direct referral arm of the CONSERVE trial (57% lower costs). In the CCTA-guided arm, follow-up stress testing was applied and contributed to reduced referrals to ICA. A recent tiered testing strategy was evaluated in both the CRESCENT I and II trials. 2, 4 From the CRES-CENT I trial, CAC was used as the index test, with follow-up CCTA used only in patients with detectable CAC or for those with a high pretest risk. 2 In this trial, nearly 40% of patients did not undergo CCTA, which reduced diagnostic evaluation costs; no events were reported in this subgroup. By comparison, nearly half of those randomized to the exercise ECG had additional confirmatory diagnostic testing. Overall, 1-year costs were significantly lower in the CAC tiered testing protocol (16% cost savings; P < 0.0001). 2 Moreover, 1-year MACE-free survival was higher in the CAC-guided testing arm (97%) compared with exercise ECG (90%; HR: 0.32; P=0.011).

5.3.2. Exercise Electrocardiographic Cost-Value Considerations

The economic evidence for the exercise ECG supports that tiered testing may offset its reduced diagnostic accuracy. 1, 2 In a decision model, tiered testing of exercise ECG followed by selective stress echocardiography resulted in improved diagnostic accuracy and favorable cost-effective ratios when compared with other testing strategies. 2 In a Medicare cohort, observed 180-day costs were lowest for the exercise ECG when compared with stress echocardiography, MPI, or CCTA. 3 Randomized trial data on cost are available and from the PROMISE trial initial test costs were $174 for exercise ECG, > 50% lower than that of other imaging procedures. 4 At 3-years of follow-up, the mean cost difference was $1731 higher for CCTA (n=4818) when compared with the exercise ECG (n=858); however, the 95% CIs for cost differences was wide ($2 to $3519), and there was no overall difference by randomization. 4 Overall, results from the PROMISE trial showed that stress testing was associated with similar costs and CAD outcomes over ∼3 years of follow-up. 4, 5 In a randomized trial of 824 symptomatic women, cumulative procedural costs were nearly 50% lower for exercise ECG versus MPI SPECT (P < 0.0001), with no difference in 2-year eventfree survival (P=0.59). 6

5.3.3. Stress Echocardiographic Cost-Value Considerations

Several cost-effectiveness models have reported an increased incremental cost-effectiveness ratio for stress echocardiography, compared with exercise ECG and

2] [3] [4] In these models, costeffectiveness was influenced by an improved diagnostic accuracy for stress echocardiography, which led to longer life expectancy. 1 In a recent systematic review, the evidence supports that stress echocardiography or stress MPI are cost-effective for those patients at intermediate pretest risk. 5 The improved CAD detection for exercise echocardiography resulted in fewer office and ED visits and hospital days, yielding a 20% cost savings when compared with the exercise ECG. 6 here were 2204 patients that underwent stress echocardiography in the PROMISE trial, and 3-year mean costs were similar to that of CCTA (CCTA -stress echocardiography mean cost difference: -$363; 95% CI: -$1562 to $818). 7 2 In the PROMISE trial, nearly two-thirds of patients underwent stress MPI, and the mean cost was similar when compared with CCTA. 3 Mean costs were also similar in a randomized trial of 457 patients comparing stress MPI with exercise ECG (P > 0.05). 4 Among higher-likelihood patients in the UK enrolled in the CECaT (Cost Effectiveness of Noninvasive Cardiac Testing) trial, MPI SPECT was the most cost-effective approach. 5

5.3.5. Stress CMR Cost-Value Considerations

A synthesis of this cost evidence reveals a pattern whereby CMR perfusion and scar imaging is associated with a favorable incremental cost-effectiveness ratio of < $50 000 per quality-adjusted life years saved. 1, 2 From a single report, a CMR strategy informed by the CE-MARC trial was more cost-effective than stress MPI, largely because of the higher diagnostic accuracy for CMR. 2 However, the most cost-effective strategy was that of initial exercise ECG followed by selective stress CMR and invasive angiography; for this tiered testing approach, additional testing was deemed appropriate in the setting of abnormal or inconclusive findings. In a decision model for intermediate pretest risk patients, a strategy of CMR followed by selective ICA had projected reduced costs by ∼25% when compared with direct referral to ICA. 2, 3 From the Stress CMR Perfusion Imaging in the United States registry, 4 patients with negative findings for ischemia and scar had low downstream costs. 5

6. EVIDENCE GAPS AND FUTURE RESEARCH

Chest pain is one of the most common symptoms for which a person seeks medical care, and it should therefore be the target of substantial research investigation. 1. For patients with ACS, considerable success has been achieved in reducing door-to-balloon times for STEMI, but little progress has been made in reducing the important delays from symptom onset to presentation. Further research is needed to develop approaches to shorten this interval including studies of other methods of evaluating patients with chest pain using technologies that permit acquisition and transmission of ECGs from home and remote evaluations (eg, telehealth) for those with acute symptoms. 1,2 2. An important, increasing patient population includes women and men with angina and ACS associated with angiographically normal or nonobstructive coronary arteries. 3, 4 Prognosis is not benign, pathophysiology has not been clarified, and optimal therapy is unclear in these heterogeneous groups, which are now considered in terms of INOCA 5 and MINOCA. 6 Adequately identifying patients with INOCA, and completing an evaluation to make such a diagnosis, is necessary but often not done, regardless of whether chest pain is assessed in the ED, inpatient, or outpatient setting. Further investigation to clarify disease mechanisms in these challenging syndromes is needed to provide the basis for therapeutic advances. 3. One of the initial challenges in the evaluation of patients with chest pain, either in the emergency or office setting, is symptom classification. Methods to elicit symptoms and clusters of symptoms that provide improved pretest probabilities of symptomatic CAD may be aided with machinelearning algorithms. It is already clear that some common dogma about chest pain descriptions, such as differences between men and women, may not be as prevalent as has been reported 7 and may impede care of both sexes if they do not fit preconceived notions of the clinical significance of their symptoms. However, reducing the differences in both sex and racial differences in treatment and outcomes are important future goals of research and clinical care. 4. Clinical risk stratification and decision tools will likely continue to grow in popularity because they are incorporated into electronic health records, but it would be useful to test them in large randomized trials to rigorously determine their

benefit in terms of improved outcomes or lower costs before widespread implementation. 1 hs-cTn assays are now the global standard of care for identifying myocardial injury, although questions remain about whether minimal elevations, which carry prognostic value, are actionable in a manner that improves outcomes. Trials evaluating various medical and procedural strategies would be useful including diagnostic and therapeutic algorithms for MINOCA. The number of potential questions that could be addressed will demand innovative trial designs to use resources efficiently and meaningfully. 5. Increasingly, randomized trials will be performed to determine which diagnostic tests can be eliminated from initial and follow-up care, both to streamline management algorithms and to decrease health care costs. In part, this approach will encompass evaluation of where patients with chest pain should be initially evaluated and monitored. Comparison of the various imaging modalities in randomized trials should help refine test selection and use. 8 0] [11] [12] In the future, registries will more frequently serve as platforms within which to conduct randomized trials. Accreditation activities coupled with registry participation will also need to be evaluated to determine if they not only improve processes of care but also affect clinical endpoints. 12 ssessment of long-term outcomes, patientcentered metrics, and cost will be integrated into these studies to enhance the evidence base for care of patients presenting with chest pain with greater precision.

|of adverse events, radiation exposure, costs, and| |---|

|alternative options should be provided to facilitate|

|the discussion.|

|5. Testing Not Needed Routinely for Low-Risk|

|Patients. For patients with acute or stable chest|

|pain determined to be low risk, urgent diagnostic|

|testing for suspected coronary artery disease is|

|not needed.|

|6. Pathways. Clinical decision pathways for chest|

|pain in the emergency department and outpatient|

|settings should be used routinely.|

|7. Accompanying Symptoms. Chest pain is the|

|dominant and most frequent symptom for both|

|men and women ultimately diagnosed with acute|

|coronary syndrome. Women may be more likely|

|to present with accompanying symptoms such as|

|nausea and shortness of breath.|

|8. Identify|

|abdo-|

|men, or jaw, as well as shortness of breath and|

|fatigue should all be considered anginal equivalents.|

|2. High-Sensitivity Troponins Preferred. High-|

|sensitivity cardiac troponins are the preferred|

|standard for establishing a biomarker diagnosis of|

|acute myocardial infarction, allowing for more accu-|

|rate detection and exclusion of myocardial injury.|

|3. Early Care for Acute Symptoms. Patients|

|with acute chest pain or chest pain equivalent|

|symptoms should seek medical care immediately|

|by calling 9-1-1. Although most patients will not|

|have a cardiac cause, the evaluation of all patients|

|should focus on the early identification or exclusion|

|of life-threatening causes.|

|4. Share the Decision-Making. Clinically stable|

|patients presenting with chest pain should be|

|included in decision-making; information about risk|

|Nature| |---|

|Anginal symptoms are perceived as retrosternal chest discomfort (eg, pain,|

|discomfort, heaviness, tightness, pressure, constriction, squeezing) (Section|

|1.4.2, Defining Chest Pain).|

|2.1.3. Considerations for Diverse Patient||| |---|---|---|

|Populations With Chest Pain|Populations With Chest Pain|Populations With Chest Pain|

|Recommendations for Considerations for Diverse Patient Populations|||

|With Chest Pain|||

|COR|LOE|Recommendations|

|||1. Cultural competency training is|

|||recommended to help achieve the best|

|1|C-LD|outcomes in patients of diverse racial and|

|||ethnic backgrounds who present with chest|

|||pain.|

|Clinical Syndrome|Findings| |---|---|

|Emergency||

|ACS|Diaphoresis, tachypnea, tachycardia, hypoten-|

||sion, crackles, S3, MR murmur. 2 ; examination|

||may be normal in uncomplicated cases|

|PE|Tachycardia + dyspnea- > 90% of patients; pain|

||with inspiration 7|

|Exercise ECG|Stress Nuclear 1 *|Stress Echocardiography 2-5|Stress CMR 6|CCTA 7 *| |---|---|---|---|---|

|Parkinson-White pattern, ventricular paced rhythm (unless test is performed to establish exercise capac-ity and not for diagnosis of ischemia) Unable to achieve ≥5 METs or unsafe to exercise High-risk unstable angina or AMI ( < 2 d) ie, active ACS Uncontrolled heart failure Significant cardiac ar-rhythmias (eg, VT, complete atrioventricular block) or high risk for arrhythmias caused by QT prolongation Severe symptomatic aortic Severe systemic arterial mm Hg) Acute illness (eg, acute PE, acute myocarditis/pericardi-hypertension (eg, ≥200/110 stenosis|Contraindications to vasodi-lator administration Significant arrhythmias (eg, VT, second-or third-degree atrioventricular block) or si-nus bradycardia < 45 bpm Significant hypotension (SBP < 90 mm Hg) Known or suspected bronchoconstrictive or bronchospastic disease Recent use of dipyridam-ole or dipyridamole-con-taining medications Use of methylxanthines ≥200/110 mm Hg) rial hypertension (eg, Severe systemic arte-adenosine, regadenoson Known hypersensitivity to (eg, aminophylline, caf-feine) within 12 h|rate Uncontrolled heart failure High-risk unstable angina, active ACS or AMI ( < 2 d) Serious ventricular ar-rhythmia or high risk for ar-rhythmias attributable to QT prolongation Respiratory failure Severe COPD, acute pulmo-nary emboli, severe pulmo-nary hypertension Contraindications to dobu-tamine (if pharmacologic stress test needed) Hemodynamically significant tis, acute aortic dissection) acute myocarditis/pericardi-Acute illness (eg, acute PE, Critical aortic stenosis † Atrioventricular block, un-controlled atrial fibrillation|lator administration Implanted devices not safe for CMR or producing ar-tifact limiting scan quality/ interpretation Significant claustrophobia Caffeine use within past 12 h|breath-hold instructions Clinical instability (eg, acute respiratory distress, severe hypotension, unstable ar-rhythmia) Renal impairment as defined by local protocols Contraindication to beta blockade in the presence of an elevated heart rate and no alternative medications available for achieving target heart rate Heart rate variability and ar-rhythmia Contraindication to nitroglyc-erin (if indicated)|

|tis, acute aortic dissection)||LV outflow tract obstruction|||

|||Contraindications to atro-|||

|||pine use:|||

|||Narrow-angle glaucoma|||

|||Myasthenia gravis|||

|||Obstructive uropathy|||

|||Obstructive gastrointestinal|||

|||disorders|||

|||Severe systemic arterial|||

|||hypertension (eg, ≥200/110|||

|||mm Hg)|||

|||Use of Contrast|||

|||Contraindicated in:|||

|||Hypersensitivity to perflutren|||

|||Hypersensitivity to blood,|||

|||blood products, or albumin|||

|||(for Optison only)|||

||||ADAPT|||2016 ESC/| |---|---|---|---|---|---|---|

||HEART Pathway 31|EDACS 44|(mADAPT) 45|NOTR 34|2020 ESC/hs-cTn* 46,47|GRACE 11,38|

|||ACS, CP > 5|ACS, CP > 5|ACS, ECG,||planned serial tro-|

|||min, planned|min, planned|troponin or-||ponin|

|||serial tro-|observation|dered|||

|||ponin|||||

||increasing missed 30-d or|charge rate|rate without in-|sification with-|30-d MACE|AMI|

||1-y MACE|without|creasing missed|out increasing|||

|||increasing|30-d MACE|missed 30-d|||

|||missed 30-d||MACE|||

|||MACE|||||

|Patients with primary|6-22|12|15|5-8|9.8|10-17|

|outcome in study popu-|||||||

|lation, %|||||||

|Variables used|History|Age|TIMI score 0-1|Age|History|Age|

||ECG Age Risk factors|Sex Risk factors History|No ischemic ECG changes Troponin (0, 2 h)|Risk factors Previous AMI or CAD|ECG hs-cTn (0, 1 or 2 h)|HR, SBP Serum Cr Cardiac arrest ECG|

||Troponin (0, 3 h)|Troponin (0, 2 h)||Troponin (0, 2 h)||Cardiac biomarker Killip class|

|Risk thresholds:|||||||

|Low risk|HEART score < 3|EDACS|TIMI score|Age < 50 y||Chest pain free,|

||Neg 0, 3-h cTn Neg 0, 2-h hs-cTn|score < 16 Neg 0, 2 h hs-cTn No ischemic ECG Δ|0 (or < 1 for mADAPT) Neg 0, 2-h cTn or hs-cTn No ischemic|< 3 risk factors Previous AMI or CAD Neg cTn or hs-cTn (0, 2 h)||GRACE < 140 Sx < 6 h -hs-cTn < ULN (0, 3 h) Sx > 6 h -hs-cTn < ULN (arrival)|

||||ECG Δ||||

||||||"low" and "high"|ng/L or|

||||||And/Or|1-h Δ = 3-5 ng/L|

||||||1-or 2-h hs-cTn Δ is||

||||||between low and||

||||||high thresholds||

|High risk|HEART score 7-10 48,49|NA|TIMI score 5-7 49 NA|Initial hs-cTn is "high"|T0 hs-cTn > 52 ng/L||

||||||Or|Or|

||||||1-or 2-h hs-cTn Δ|Δ 1 h > 5 ng/L|

||||||is high||

||(40% versus 18%) ↓ 30-d objective testing by 12% (69% versus 57%) ↓ length of stay by 12 h (9.9 versus 21.9 h)|identified as low risk ver-sus ADAPT (42% versus 31%)|discharged ≤6 h (19% versus 11%)|sensitivity =100% 28% eligible charge for ED dis-|62% Ruled out (0.2% 30-d MACE) 13% Rule in 25% Observe|> 99% 30-d MACE not studied|

|AMI sensitivity, %|100|100|100|100|> 99|96.7|

|cTn accuracy: 30-d|100|100|100|100|NA|NA|

|MACE sensitivity, %|||||||

|hs-cTn accuracy: 30-d|95|92|93|99|99|--|

|ED discharge, %|40|49|19 (ADAPT)|28|--|--|

||||39 (mADAPT)||||

|||Warranty| |---|---|---|

|Test Modality|Result|Period|

|Anatomic|Normal coronary angiogram|2 y|

||CCTA with no stenosis or plaque||

|Stress testing|Normal stress test (given adequate stress) 1 y|Normal stress test (given adequate stress) 1 y|

|Table 8 provides a definition used for low-risk chest pain patients. CCTA|||

|indicates coronary computed tomographic angiography.|||

||Low Risk ( < 1% 30-d Risk for Death or| |---|---|

||MACE)|

|hs-cTn Based||

|T-0|T-0 hs-cTn below the assay limit of detection|

||or "very low" threshold if symptoms present for|

||at least 3 h|

|T-0 and 1-or 2-h Delta|T-0 hs-cTn and 1-or 2-h delta are both below|

||the assay "low" thresholds ( > 99% NPV for|

||30-d MACE)|

|Clinical Decision Pathway Based|Clinical Decision Pathway Based|

|HEART Pathway 20|HEART score ≤3, initial and serial cTn/hs-cTn|

||< assay 99th percentile|

|EDACS 14|EDACS score ≤16; initial and serial cTn/hs-cTn|

|ADAPT 21|TIMI score 0, initial and serial cTn/hs-cTn|

|mADAPT|TIMI score 0/1, initial and serial cTn/hs-cTn|

|NOTR 15|0 factors|

|ADAPT indicates 2||

|COR|LOE|Recommendations| |---|---|---|

|Recommendations for High-Risk Patients, Including Those With|||

|High-Risk Findings on CCTA or Stress Testing|||

|||1. For patients with acute chest pain and|

|||suspected ACS who have new ischemic|

|||changes on electrocardiography, troponin-|

|||confirmed acute myocardial injury, new-|

|1|B-NR|onset left ventricular systolic dysfunction (ejection fraction < 40%), newly diagnosed|

|||moderate-severe ischemia on stress testing,|

|||hemodynamic instability, and/or a high clinical|

|||decision pathway (CDP) risk score should be|

|||designated as high risk for short-term MACE. 1-3|

|||2. For patients with acute chest pain and|

|1|C-EO|suspected ACS who are designated as high|

|||risk, ICA is recommended. 4-7|

|||3. For high-risk patients with acute chest pain|

|||who are troponin positive in whom obstructive|

|2a|B-NR|CAD has been excluded by CCTA or ICA,|

|||CMR or echocardiography can be effective in|

|||establishing alternative diagnoses. 8-12|

|Recommendation for Evaluation of Acute Chest Pain in Patients With| |---|

|Cocaine and Methamphetamine Use|

|Referenced studies that support the recommendation are summarized|

|in Online Data Supplement 21.|

|4.1.7. Shared Decision-Making in Patients With||| |---|---|---|

|Acute Chest Pain|||

|Recommendations for Shared Decision-Making in Patients With Acute|||

|Chest Pain|||

|Referenced studies that support the recommendations are|||

|summarized in Online Data Supplement 22.|||

|||suspected ACS who are deemed low risk by|

|1|B-R|a CDP, patient decision aids are beneficial to|

|||improve understanding and effectively facilitate|

|||risk communication. 1,2|

|||suspected ACS who are deemed intermediate|

|||risk by a CDP, shared decision-making|

|||between the clinician and patient regarding|

|1|B-R|the need for admission, for observation,|

|||discharge, or further evaluation in an|

|||outpatient setting is recommended for|

|||improving patient understanding and reducing|

|||low-value testing. 1,2|

|4| |---|

|Respiratory| |---|

|Pulmonary embolism|

|Pneumothorax/hemothorax|

|Pneumomediastinum|

|Pneumonia|

|Bronchitis|

|Pleural irritation|

|Malignancy|

|Gastrointestinal|

|Cholecystitis|

|Pancreatitis|

|Hiatal hernia|

|Gastroesophageal reflux disease/gastritis/esophagitis|

|Peptic ulcer disease|

|Esophageal spasm|

|Dyspepsia|

|Chest wall|

|Costochondritis|

|Chest wall trauma or inflammation|

|Herpes zoster (shingles)|

|Cervical radiculopathy|

|Breast disease|

|Rib fracture|

|Musculoskeletal injury/spasm|

|Psychological|

|Panic disorder|

|Anxiety|

|Clinical depression|

|Somatization disorder|

|Hypochondria|

|Other|

|Hyperventilation syndrome|

|Carbon monoxide poisoning|

|Sarcoidosis|

|Lead poisoning|

|Prolapsed intervertebral disc|

|Thoracic outlet syndrome|

|Adverse effect of certain medications (eg, 5-fluorouracil)|

|Sickle cell crisis|

|Gulati et al|2021 Chest Pain Guideline|2021 Chest Pain Guideline| |---|---|---|

|Sequential or Add-on Testing: What to Do if Index Test Results are Positive or|||

|Inconclusive (continued)|||

||November 30, 2021|e43|

|5.2. Patients With Known CAD Presenting With||| |---|---|---|

|Stable Chest Pain|||

|Recommendations for Patients With Known CAD Presenting With|||

|Stable Chest Pain|Stable Chest Pain||

|summarized in Online Data Supplement 31.|summarized in Online Data Supplement 31.|summarized in Online Data Supplement 31.|

|||1. For patients with obstructive CAD and stable|

|1|A|chest pain, it is recommended to optimize|

|||GDMT. 1-3|

|||2. For patients with known nonobstructive CAD|

|1|C-EO|and stable chest pain, it is recommended to|

|||optimize preventive therapies. 4,5|

||November 30, 2021|e45|

|CLINICAL STATEMENTS CLINICAL STATEMENTS CLINICAL STATEMENTS|AND GUIDELINES AND GUIDELINES AND GUIDELINES|ACC/AHA JOINT COMMITTEE MEMBERS Patrick T. O'Gara, MD, MACC, FAHA, Chair; Joshua A. Beckman, MD, MS, FAHA, FACC, Chair-Elect; Glenn N. Levine, MD, FACC, FAHA, Immediate Past Chair*; Sana M. Al-Khatib, MD, MHS, FACC, FAHA#; Anastasia L. Armbruster, PharmD, FACC; Kim K. Birtcher, MS, PharmD, AACC*; Ralph G. Brindis, MD, MPH, MACC#; Joaquin E. Cigarroa, MD, FACC*; Lisa de las Fuentes, MD, MS, e54 Gulati et al ARTICLE INFORMATION REFERENCES PREAMBLE 1. Intitute of Medicine (US) Committee on Standards for Developing Trustwor-thy Clinical Practice Guidelines. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press. 2011. vascular Medicine, Heart and Vascular Institute Hani Jneid Baylor College of Medi-cine-Associate Professor of Medicine; The Michael DeBakey VA Medical Cen-ter-Director of Intervention-al Cardiology Research None None 2. November 30, 2021 FASE, FAHA; Anita Deswal, MD, MPH, FACC, FAHA; Dave L. Dixon, PharmD, FACC*; Lee A. Fleisher, MD, FACC, FAHA*; Federico Gentile, MD, FACC*; Zachary D. Goldberger, MD, MS, FACC, FAHA*; Bulent Gorenek, MD, FACC; Norrisa Haynes, MD; Adrian F. Hernandez, MD; Mark A. Hlatky, MD, FACC, FAHA*; John S. Ikonomidis, MD, PhD, FAHA#; José A. Joglar, MD, FAHA, FACC; W. Schuyler Jones, MD, FACC; Joseph E. Marine, MD, FACC*; Daniel B. Mark, MD, MPH, FACC; Debabrata Mukherjee, MD, MS, FACC, FAHA; Latha P. Palaniappan, MD, MS, FAHA, FACC; Mariann R. Piano, RN, PhD, FAHA; Tanveer Rab, MD, FACC; Barbara Riegel, PhD, RN, FAHA*; Erica S. Spatz, MD, MHS, FACC; Jacqueline E. Tamis-Holland, MD, FACC; Duminda N. Wijeysundera, MD, PhD*; Y. Joseph Woo, MD, FAHA, FACC STAFF American College of Cardiology Dipti N. Itchhaporia, MD, FACC, President Cathleen C. Gates, Chief Executive Officer MaryAnne Elma, MPH, Senior Director, Enterprise Con-tent and Digital Strategy Timothy W. Schutt, MA, Clinical Practice Guidelines Analyst Grace D. Ronan, Team Leader, Clinical Policy Publications American College of Cardiology/American Heart Association Thomas S.D. Getchius, Director, Guideline Strategy and Operations Abdul R. Abdullah, MD, Director, Guideline Science and Methodology Hannah Planalp, Guideline Advisor Zainab Shipchandler, MPH, Guideline Advisor American Heart Association Mitchell S.V. Elkind, MD, MS, FAAN, FAHA, President Nancy Brown, Chief Executive Officer Mariell Jessup, MD, FAHA, Chief Science and Medical Officer Radhika Rajgopal Singh, PhD, Senior Vice President, Of-fice of Science and Health Paul St. Laurent, DNP, RN, Senior Science and Medicine Advisor, Office of Science, Medicine and Health Jody Hundley, Production and Operations Manager, Sci-entific Publications, Office of Science Operations 0000000000001029 2021 Chest Pain Guideline e55 • PLx Pharma* • Regeneron* • Roche* • Sanofi-aventis* • Synaptic* • Takeda † • The Medicines Company* (Continued ) November 30, 2021 e79 None None None None Gulati et al 2021 Chest Pain Guideline 14. Gulati et al 2021 Chest Pain Guideline 3.1. Anatomic Testing 3.1.1. Coronary Computed Tomography Angiography 2021 Chest Pain Guideline • Apex Innovation* • AstraZeneca • AstraZeneca, Hospital Quality Foundation • Beckman Coulter • Boehringer Ingelheim • Bristol-Myers Squibb • Cardiorentis • Novartis* • Ortho Diagnostics* • Pfizer • Roche* • Sciex • Shire* • Siemens* • The Medicines Company • Trevena • ZS Pharma None • Carbon Lifeform Innovations † • Mespere † • Amgen* • Bristol-Myers Squibb* • Cardiorentis* • Edwards Life-sciences* • Gilead Sciences* • Novartis* • Pfizer* • Roche* • Shire* • Trevena • Amgen* • Edwards* • E.R. Squibb & Sons, L.L.C. • Janssen Pharmaceuticals • Roche None Debabrata Mukherjee (Vice Chair) Texas Tech University Health Sciences Center El Paso-Chairman, De-partment of Medicine None None None None None None Ezra Amsterdam UC Davis Medical Cen-ter-Professor, Depart-ment of Internal Medicine None None None None None None Deepak L. Bhatt Brigham and Women's Hospital Heart & Vascular Center-Executive Direc-tor of Interventional Car-diovascular Programs; Harvard Medical School-Professor of Medicine • Daiichi Sankyo • Pfizer* None None • Abbott* • Amarin* • Amgen* • AstraZeneca* • Bayer* • Boehringer Ingel-heim* • Bristol-Myers Squibb* • Cardax* • Chiesi* • Eisai* • Eli Lilly* • Ethicon* • FlowCo † • Forest Labora-tories* • Idorsia* • Ironwood* • Ischemix* • Medtronic* • Merck* • Pfizer* • PhaseBio* • Amarin Pharma Inc.* • AstraZeneca* • Biotronik ‡ • Boehringer Ingelheim* • Boston Scien-tific ‡ • Cardax † • Merck † • Novartis • PhaseBio † • PLx Pharma † • Regado Biosci-ences † • Sanofi-aventis* • St. Jude Medi-cal ‡ • Svelte ‡ None Gulati et al 2021 Chest Pain Guideline Kim K. Birtcher University of Houston College of Pharmacy-Clinical Professor None None None None None None Ron Blankstein Harvard Medical School-Associate Professor of Medicine and Radiology, Co-Director, Cardiovas-cular Imaging Training Program; Brigham and Women's Hospital-Asso-ciate Physician, Preven-tive Cardiology; Director, Cardiac Computed Tomography • Amgen • Astellas Inc • EKOS Corp. None None • Amgen † • Astellas Pharma † • Gilead Sciences † • Sanofi-aventis † • Sanofi US Ser-vices* None Jack Boyd Stanford University-Clini-cal Assistant Professor, Department of Cardiotho-racic Surgery • Esculon/Centese • Sorin None None None None None Renee P. Bullock-Palmer Deborah Heart & Lung Center-Director, Wom-en's Heart Center; Direc-tor, Non-Invasive Cardiac Imaging None None None None None None Theresa Conejo Nazareth Hospital-Heart Failure Coordinator None None None None None None Deborah B. Diercks UT Southwestern-Pro-fessor and Chair, De-partment of Emergency Medicine •` ETHealthcare • Janssen Pharmaceu-ticals • Novartis* None None • Abbott* • Bristol-Myers Squibb † • Ortho Clinical † • Roche* • Siemens • E.R. Squibb & Sons, L.L.C.* • Konica Minolta Healthcare Americans, Inc. None Federico Gentile Centro Cardiologico Gen-tile, Naples, Italy-Director None None None None None None John P. Greenwood Leeds Institute of Cardio-vascular and Metabolic Medicine-Mautner Chair of Cardiology, Division of Biomedical Imaging None None None None None None Erik P. Hess University of Alabama at Birmingham-Professor of Emergency Medicine and Vice Chair for Research, Department of Emer-gency Medicine • Gilead Sciences* None None • Gilead Sciences* None None Steven M. Hollenberg Cooper Medical School of Rowan University-Profes-sor of Medicine; Cooper University Hospital-Direc-tor, Coronary Care Unit None None None None None None Wael A. Jaber Cleveland Clinic Le-rner College of Medicine-Professor of Medicine, De-partment of Cardiovascular Medicine and Fuad Jubran Endowed Chair in Cardio-None None None None None None 1. Gaur S, Gulati et al Appendix 1. Continued|AND GUIDELINES AND GUIDELINES|CLINICAL STATEMENTS CLINICAL STATEMENTS| |---|---|---|---|---|

Patients with acute or stable chest pain who are at intermediate risk or intermediate to high pre-test risk of obstructive coronary artery disease, respectively, will benefit the most from cardiac imaging and testing. 9.

The physician should have a heightened awareness to understand that these symptoms may be associated with ACS, in addition to chest pain.1

-hour Accelerated Diagnostic Protocol to Access Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarkers; cTn, cardiac troponin; EDACS, Emergency Department Acute Coronary Syndrome; HEART Pathway, History, ECG, Age, Risk Factors, Troponin; hs-cTn, high-sensitivity cardiac troponin; MACE, major adverse cardiovascular events; mADAPT, modified 2-hour Accelerated Diagnostic Protocol to Access Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarkers; NOTR, No Objective Testing Rule; NPV, negative predictive value; and TIMI, Thrombolysis in Myocardial Infarction.

3. High-Risk Patients With Acute Chest PainRecommendations for High-Risk Patients With Acute Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplements 18 and 19.

1. Because the risk of CAD is relatively high in patients undergoing dialysis, when acute unremitting chest pain occurs during dialysis, a 12-lead ECG should be performed and the patient should be urgently transferred by EMS to an acute care setting for evaluation for cause of symptoms and further clinical engagement.

Cocaine and methamphetamine use can be considered in young patients presenting with chest pain and evidence of ACS; the frequency of ACS is < 10% among cocaine and methamphetamine users in most studies, and death is rare. 1-4 A person's urine typically tests positive for cocaine or methamphetamine within 1 to 4 hours of consuming the drug and will continue to test positive for 2 to 4 days.

Recommendations for Intermediate-High Risk Patients With Stable Chest Pain and No Known CAD (Continued)

35,[111][112] [113]10. 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.

6,72. For all patients with a history of CAD risk factors, optimized preventive therapy should be

This document was approved by the American College of Cardiology Clinical Policy Approval Committee in May 2021, the American Heart Association Science Advisory and Coordinating Committee in May 2021, the Society of Cardiovascular Computed Tomography in July 2021, the Society for Academic Emergency Medicine in June 2021, the Society for Cardiovascular Magnetic Resonance in June 2021, the American College of Chest Physicians in June 2021, the American Society of Echocardiography in June 2021, the American Heart Association Executive Committee in July 2021, and the American College of Cardiology Science and Quality Committee in July 2021.The Comprehensive RWI Data Supplement table is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000001029/-/DC1.This article has been copublished in the Journal of the American College of Cardiology.Copies: This document is available on the websites of the American Heart Association (professional.heart.org)and the American College of Cardiology (www.acc.org).A copy of the document is also available at https://professional. heart.org/statementsbyselecting the "Guidelines & Statements" button.To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com.The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations.For more on AHA statements and guidelines development, visit https://professional.heart.org/statements.Select the "Guidelines & Statements" drop-down menu near the top of the webpage, then click "Publication Development."Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the "Copyright Permissions Request Form" appears in the second paragraph (https://www.heart.org/en/aboutus/statements-and-policies/copyright-request-form). Institute of Medicine (US) Committee on Standards for Systematic Reviews of Comparative Effectiveness Research. Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: National Academies Press. 2011. 3. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. Circulation. 2014;129:2329-2345. 4. ACCF/AHA Task Force on Practice Guidelines. Methodology manual and policies from the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Available at: https://www.acc.org/Guidelines/About-Guidelines-and-Clinical-Documents/Methodology. Accessed July 26, 2021. https://professional.heart. org/-/media/phd-files/guidelines-and-statements/methodology_manual_ and_policies_ucm_319826.pdf. 5. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;133:1426-1428. 6. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and US Department of Health and Human Services. J Am Coll Cardiol. 2014;64:1851-1856. 7. Levine GN, O'Gara PT, Beckman JA, et al. Recent innovations, modifications, and evolution of ACC/AHA Clinical Practice Guidelines: an update for our constituencies: a report of the American College of Cardiology/Ameri-can Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;129:e879-e886. 1.4. Scope of the Guideline 1. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/ PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2014;130:1749-1767. 2. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126:e354-e471. 3. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:e199-e267. 4. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019;140:e125-e151. 5. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:e344-e426. 6. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-e1143. 7. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128:e240-e327. 8. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137-e161. 9. Arnett DK, Blumenthal R, Albert M, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596-e646. 10. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(suppl 2):S102-S138. 11. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362-e425. 12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2018;138:e272-e391. 13. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/ AHA guideline for coronary artery bypass graft surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124:e652-e735. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142:e558-e631. 15. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574-e651. 16. Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/ AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation. 2016;133:1135-1147. 17. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;58:2458-2473. 18. Berg KM, Cheng A, Panchal AR, et al. Part 7: systems of care: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020;142:S580-S604. 19. Panchal AR, Berg KM, Hirsch KG, et al. 2019 American Heart Association focused update on advanced cardiovascular life support: use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest: an update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2019;140:e881-e894. 20. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-e115. 21. Amsterdam EA, Kirk JD, Bluemke DA, et al. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation. 2010;122:1756-1776. 22. Fox CS, Golden SH, Anderson C, et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2015;132:691-718. 23. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices-United States, 2018-19 Influenza Season. MMWR Recomm Rep. 2018;67:1-20. . Wolk MJ, Bailey SR, Doherty JU, et al. ACCF/AHA/ASE/ASNC/HFSA/ HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2014;63:380-406. 2. Medicare Program: Changes to Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs; Revisions of Organ Procurement Organizations Conditions of Coverage; Prior Authorization Process and Requirements for Certain Covered Outpatient Department Services; Potential Changes to the Laboratory Date of Service Policy; Changes to Grandfathered Children's Hospitals-Within-Hospitals; Notice of Closure of Two Teaching Hospitals and Opportunity To Apply for Available Slots. Available at: https://www.cms.gov/ Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/ Hospital-Outpatient-Regulations-and-Notices-Items/CMS-1717-FC. Accessed September 14, 2020. Ovrehus KA, Dey D, et al. Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions. Eur Heart J. 2016;37:1220-1227. 2. Ferencik M, Mayrhofer T, Bittner DO, et al. Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: a secondary analysis of the PROMISE randomized clinical trial. JAMA Cardiol. 2018;3:144-152. 3. Budoff MJ, Mayrhofer T, Ferencik M, et al. Prognostic value of coronary artery calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Circulation. 2017;136:1993-2005. . Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126:e354-e471. 2. Shaw LJ, Hage FG, Berman DS, et al. Prognosis in the era of comparative effectiveness research: where is nuclear cardiology now and where should it be? J Nucl Cardiol. 2012;19:1026-1043. 3. Green R, Cantoni V, Petretta M, et al. Negative predictive value of stress myocardial perfusion imaging and coronary computed tomography angiography: a meta-analysis. J Nucl Cardiol. 2017. 4. Rozanski A, Gransar H, Min JK, et al. Long-term mortality following normal exercise myocardial perfusion SPECT according to coronary disease risk factors. J Nucl Cardiol. 2014;21:341-350. 5. Metz LD, Beattie M, Hom R, et al. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis. J Am Coll Cardiol. 2007;49:227-237. 6. Dorbala S, Di Carli MF, Beanlands RS, et al. Prognostic value of stress myocardial perfusion positron emission tomography: results from a multicenter observational registry. J Am Coll Cardiol. 2013;61:176-184. 7. Kay J, Dorbala S, Goyal A, et al. Influence of sex on risk stratification with stress myocardial perfusion Rb-82 positron emission tomography: results from the PET (Positron Emission Tomography) Prognosis Multicenter Registry. J Am Coll Cardiol. 2013;62:1866-1876. 8. Shaw LJ, Cerqueira MD, Brooks MM, et al. Impact of left ventricular function and the extent of ischemia and scar by stress myocardial perfusion imaging on prognosis and therapeutic risk reduction in diabetic patients with coronary artery disease: results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. J Nucl Cardiol. 2012;19:658-669. 9. Gould KL, Johnson NP, Bateman TM, et al. Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making. J Am Coll Cardiol. 2013;62:1639-1653. Downloaded from http://ahajournals.org by on October 28, 2021 Circulation. 2021;144:00-00. DOI: 10.1161/CIR.0000000000001029

None

Washington University

References

引用 / 出处

2021 AHA／ACC／ASE／CHEST／SAEM／SCCT／SCMR指南：胸痛的诊断和评估（全文）. 2021.

2021 AHA／ACC／ASE／CHEST／SAEM／SCCT／SCMR指南： 胸痛的诊断和评估（全文）

Authors

Keywords

1. INTRODUCTION 1.Methodology and Evidence Review

1.2. Organization of the Writing Committee

CLINICAL STATEMENTS AND GUIDELINES

1.4.2. Defining Chest Pain

COR LOE Recommendations 1 B-NR

Synopsis

CLINICAL STATEMENTS AND GUIDELINES

2.1.1. A Focus on the Uniqueness of Chest Pain in Women

COR LOE Recommendations

Onset and duration

Location and radiation

Severity

2.1.2. Considerations for Older Patients With Chest Pain

1 C-LD

Synopsis

3. CARDIAC TESTING GENERAL CONSIDERATIONS

CLINICAL STATEMENTS AND GUIDELINES

3.1. Anatomic Testing

3.1.1. Coronary Computed Tomography Angiography

3.1.2. Invasive Coronary Angiography

3.2.1. Exercise ECG

3.2.2. Echocardiography/Stress Echocardiography

3.2.3. Stress Nuclear (PET or SPECT) Myocardial Perfusion Imaging

3.2.4. Cardiovascular Magnetic Resonance Imaging

3.3. Cardiac Testing Considerations for Women Who Are Pregnant, Postpartum, or of Child-Bearing Age

4. CHOOSING THE RIGHT PATHWAY WITH PATIENT-CENTRIC ALGORITHMS FOR ACUTE CHEST PAIN

1 B-NR

Recommendation-Specific Supportive Text

2. The additional testing needed for intermediate-risk

Abstract

PREAMBLE

Intended Use

Clinical Implementation

Methodology and Modernization

Relationships With Industry and Other Entities

Precipitating factors

Relieving factors

2.1.4. Patient-Centric Considerations

2.2. Physical Examination

Synopsis

2.3. Diagnostic Testing

2.3.1. Setting Considerations

1 C-EO

COR LOE Recommendation 2a B-NR

4.2.1. Acute Chest Pain With Suspected Acute Aortic Syndrome

Recommendation-Specific Supportive Text

2. The ability to attain adequate 3-dimensional (3D)

4.3.2. Evaluation of Acute Chest Pain With Suspected Anxiety and Other Psychosomatic Considerations

COR LOE Recommendation

2a B-R

4.3.3. Evaluation of Acute Chest Pain in Patients With Sickle Cell Disease

5. EVALUATION OF PATIENTS WITH STABLE CHEST PAIN

5.1.3. Intermediate-High Risk Patients With Stable Chest Pain and No Known CAD

5. Use of attenuation correction algorithms and prone

5.2.1. Patients With Obstructive CAD Who Present With Stable Chest Pain

1 A

5.3. Cost-Value Considerations in Diagnostic Testing

5.3.1. CCTA and CAC Scanning Cost-Value Considerations

5.3.2. Exercise Electrocardiographic Cost-Value Considerations

5.3.3. Stress Echocardiographic Cost-Value Considerations

5.3.5. Stress CMR Cost-Value Considerations

6. EVIDENCE GAPS AND FUTURE RESEARCH

None

References

引用 / 出处

2021 AHA／ACC／ASE／CHEST／SAEM／SCCT／SCMR指南：胸痛的诊断和评估（全文）