AHA/ACC CLINICAL PRACTICE GUIDELINE 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/ SCMR Guideline for the Evaluation and Diagnosis of Chest Pain:

Circulation

AHA/ACC CLINICAL PRACTICE GUIDELINE

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/ SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Writing Committee Members*

Martha Gulati, MD, MS, FACC, FAHA, Chair†; Phillip D. Levy, MD, MPH, FACC, FAHA, Vice Chair†;

Debabrata Mukherjee, MD, MS, FACC, FAHA, Vice Chair†; Ezra Amsterdam, MD, FACC†; Deepak L. Bhatt, MD, MPH, FACC, FAHA†; Kim K. Birtcher, MS, PharmD, AACC‡; Ron Blankstein, MD, FACC, MSCCT§; Jack Boyd, MD†;

Renee P. Bullock-Palmer, MD, FACC, FAHA, FASE, FSCCT†; Theresa Conejo, RN, BSN, FAHA‖; Deborah B. Diercks, MD, MSc, FACC¶; Federico Gentile, MD, FACC#; John P. Greenwood, MBChB, PhD, FSCMR, FACC**; Erik P. Hess, MD, MSc†;

Steven M. Hollenberg, MD, FACC, FAHA, FCCP††; Wael A. Jaber, MD, FACC, FASE‡‡; Hani Jneid, MD, FACC, FAHA§§; José A. Joglar, MD, FAHA, FACC‡; David A. Morrow, MD, MPH, FACC, FAHA†; Robert E. O’Connor, MD, MPH, FAHA†; Michael A. Ross, MD, FACC†; Leslee J. Shaw, PhD, FACC, FAHA, MSCCT†

AIM: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

STRUCTURE: Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence- based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.

Key Words: AHA Scientific Statements ◼ chest pain ◼ angina ◼ coronary artery disease ◼ acute coronary syndrome ◼ myocardial ischemia ◼ myocardial infarction ◼ myocardial injury, noncardiac ◼ accelerated diagnostic pathway ◼ clinical decision pathway ◼ sex differences ◼ troponins ◼ chest pain syndromes ◼ biomarkers ◼ shared decision-making ◼ noncardiac chest pain ◼ cardiac imaging

*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 of the full guideline 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.

ACC/AHA Joint Committee on Clinical Practice Guidelines Members, see page e358.

The American Heart Association requests that this document be cited as follows: Gulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, Blankstein R, Boyd

J, Bullock-Palmer RP, Conejo T, Diercks DB, Gentile F, Greenwood JP, Hess EP, Hollenberg SM, Jaber WA, Jneid H, Joglar JA, Morrow DA, O’Connor RE, Ross MA, Shaw LJ. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144:e336–e367. doi: 10.1161/CIR.0000000000001030

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Gulati et al

2021 Chest Pain Guideline Executive Summary

CONTENTS

Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e336 Top 10 Take-Home Messages for the Evaluation

and Diagnosis of Chest Pain . . . . . . . . . . . . . . . . . e337

1. Purpose of the Executive Summary. . . . . . . . . . . e339

1.1. Document Review and Approval . . . . . . . . e340

1.2. Class of Recommendations and

Level of Evidence . . . . . . . . . . . . . . . . . . . . . . e340

1.3. Defining Chest Pain. . . . . . . . . . . . . . . . . . . . e340

2. Initial Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e340

2.1. History .. ………………………… e340

2.1.1. A Focus on the Uniqueness of

Chest Pain in Women . . . . . . . . . . . e340

2.1.2. Considerations for Older

Patients With Chest Pain. . . . . . . . e341

2.1.3. Considerations for Diverse Patient Populations With Chest Pain . . . . e341 2.1.4. Patient-Centric Considerations . . e341

2.2. Physical Examination. . . . . . . . . . . . . . . . . . . e341

2.3. Diagnostic Testing . . . . . . . . . . . . . . . . . . . . . e341

2.3.1. Setting Considerations . . . . . . . . . . e341

2.3.2. Electrocardiogram . . . . . . . . . . . . . . e342

2.3.3. Chest Radiography . . . . . . . . . . . . . e343

2.3.4. Biomarkers. . . . . . . . . . . . . . . . . . . . . e343

3. Cardiac Testing General Considerations. . . . . . . e343

4. Choosing the Right Pathway With Patient-Centric Algorithms for Acute Chest Pain . . . . . . . . . . .. . e343

4.1. Patients With Acute Chest Pain and

Suspected Acute Coronary Syndrome

(Not Including STEMI). . . . . . . . . . . . . . . .. . e343

4.1.1. Low-Risk Patients With Acute

Chest Pain . . . . . . . . . . . . . . . . . . .. . e344

4.1.2. Intermediate-Risk Patients With

Acute Chest Pain. . . . . . . . . . . . . . . e344

4.1.3. High-Risk Patients With Acute

Chest Pain . . . . . . . . . . . . . . . . . . . . . e348

4.1.4. Acute Chest Pain in Patients With

Prior Coronary Artery Bypass Graft

(CABG) Surgery. . . . . . . . . . . . . . . . e350

4.1.5. Evaluation of Patients With Acute

4.3.

Evaluation of Acute Chest Pain With Suspected Noncardiac Causes . . . . . . . . . e352

4.3.1. Evaluation of Acute Chest Pain

With Suspected Gastrointestinal

Syndromes. . . . . . . . . . . . . . . . . . . . . e353

4.3.2. Evaluation of Acute Chest Pain

With Suspected Anxiety and Other

Psychosomatic Considerations . . . . e353

4.3.3. Evaluation of Acute Chest

Pain in Patients With Sickle

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.. .. . .. ..

e350 . e350 e350 e350 e351 e351 e351

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.

Cell Disease . . . . . . . . . . . . . . . . . . . e353 Evaluation of Patients With Stable

Chest Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e353

5.1. Patients With No Known CAD

Presenting With Stable Chest Pain . . . . . . e353

5.1.2. Low-Risk Patients With Stable

ChestPainandNoKnownCAD….e354

5.1.3. Intermediate-High Risk Patients

With Stable Chest Pain and

No Known CAD . . . . . . . . . . . . . . . . e354

5.2. Patients With Known CAD Presenting

With Stable Chest Pain . . . . . . . . . . . . . . . . . e354

5.2.1. Patients With Obstructive

CAD Who Present With Stable

Chest Pain . . . . . . . . . . . . . . . . . . . . . e354

5.2.2. Patients With Known

Nonobstructive CAD Presenting

With Stable Chest Pain . . . . . . . . . e356

5.2.3. Patients With Suspected

Ischemia and No Obstructive

CAD (INOCA) . . . . . . . . . . . . . . . . . . e357 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e359

TOP 10 TAKE-HOME MESSAGES FOR THE EVALUATION AND DIAGNOSIS OF CHEST PAIN

Chest Pain Receiving Dialysis . . . .

4.1.6. Evaluation of Acute Chest Pain

in Patients With Cocaine and

Methamphetamine Use . . . . . . . . .

4.1.7. Shared Decision-Making in

Patients With Acute Chest Pain. . .

4.2. Evaluation of Acute Chest Pain With

Nonischemic Cardiac Pathologies . . . . . . .

4.2.1. Acute Chest Pain With Suspected

Acute Aortic Syndrome . . . . . . .

4.2.2. Acute Chest Pain With

Suspected Pulmonary Embolism .

4.2.3. Acute Chest Pain With

Suspected Myopericarditis . . . .

4.2.4. Acute Chest Pain With Valvular Heart Disease. . . . . . . . . . . . . . . .

. e350

Chest Pain Means More Than Pain in the Chest. Pain, pressure, tightness, or discomfort in the chest, shoulders, arms, neck, back, upper abdomen, or jaw, as well as shortness of breath and fatigue should all be considered anginal equivalents.

High-Sensitivity Troponins Preferred. High- sensitivity cardiac troponins are the preferred standard for establishing a biomarker diagnosis of acute myocardial infarction, allowing for more accurate detection and exclusion of myocardial injury.

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4. Share the Decision-Making. Clinically stable patients presenting with chest pain should be included in decision-making; information about risk 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 Patients Most Likely to Benefit

From Further Testing. 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. Noncardiac Is In. Atypical Is Out. “Noncardiac” should be used if heart disease is not suspected. “Atypical” is a misleading descriptor of chest pain, and its use is discouraged.

10. Structured Risk Assessment Should Be Used. For patients presenting with acute or stable chest pain, risk for coronary artery disease and adverse events should be estimated using evi- dence-based diagnostic protocols.

Figure 1 illustrates the take-home messages.

Figure 1. Take-Home Messages for the Evaluation and Diagnosis of Chest Pain

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1. PURPOSE OF THE EXECUTIVE SUMMARY

The charge of the writing committee was to develop a guideline for the evaluation of acute or stable chest pain or other anginal equivalents, in a variety of clinical set- tings, with an emphasis on the diagnosis on ischemic causes.1 The guideline will not provide recommendations on whether revascularization is appropriate, or what mo- dality is indicated.1 Such recommendations can be found in the forthcoming American Heart Association (AHA)/ American College of Cardiology (ACC) coronary artery revascularization guideline.1a

After injuries, chest pain is the second most com- mon reason for adults to present to the emergency

department (ED) in the United States and accounts for >6.5 million visits, which is 4.7% of all ED visits.2 Chest pain also leads to nearly 4 million outpatient vis- its annually in the United States.3 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 >365000 deaths annually.4 Distinguishing between serious and benign causes of chest pain is imperative. The life- time prevalence of chest pain in the United States is 20% to 40%,5 and women experience this symptom more often than men.6 Of all ED patients with chest

Table 1. Applying ACC/AHA Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*

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pain, only 5.1% will have an acute coronary syndrome (ACS) and more than half will ultimately be found to have a noncardiac cause.7 Nonetheless, chest pain is the most common symptom of CAD in both men and women.

1.1. Document Review and Approval

This document was reviewed by 16 official reviewers nominated by the ACC, AHA, the American College of Emergency Physicians, American Society of Echocar- diography (ASE), American Society of Nuclear Cardi- ology (ASNC), American College of Chest Physicians (CHEST), Society for Academic Emergency Medicine (SAEM), Society of Cardiovascular Computed Tomog- raphy (SCCT), and Society for Cardiovascular Magnetic Resonance (SCMR), and 39 individual content review- ers. Authors’ relationships with industry and other entities information is published in Appendix 1 of the full guide- line.1 Reviewers’ relationships with industry and other en- tities information is published in Appendix 2 of the full guideline.1

1.2. Class of Recommendations and Level of

Evidence

The Class of Recommendation (COR) indicates the strength of recommendation, encompassing the estimat- ed magnitude and certainty of benefit in proportion to risk. The Level of Evidence (LOE) rates the quality of sci- entific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 1).8

1.3. Defining Chest Pain

Figure 2 presents an index of suspicion that chest “pain” is ischemic in origin based on commonly used descriptors.

2. INITIAL EVALUATION

2.1. History

Figure 3 presents the top 10 causes of chest pain in ED based on age. Table 2 presents chest pain characteristics and corresponding causes.

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

1. Women who present with chest pain are at risk for underdiagnosis, and potential cardiac causes should always be considered.11,12,14,16-19

Recommendations for Defining Chest Pain

Referenced studies that support the recommendations are summarized in Online Data Supplements 1 and 2.

COR

LOE

Recommendations

B-NR

1. An initial assessment of chest pain is recom- mended to triage patients effectively on the basis of the likelihood that symptoms may be attributable to myocardial ischemia.9-15

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.

Recommendation for History

COR

LOE

Recommendation

C-LD

1. In patients with chest pain, a focused history that includes characteristics and duration of symptoms relative to presentation as well as associated features, and cardiovascular risk fac- tor assessment should be obtained.

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

B-NR

2. In women presenting with chest pain, it is rec- ommended to obtain a history that emphasizes accompanying symptoms that are more com- mon in women with ACS.11,12,14,16-19

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Figure 2. Index of Suspicion That Chest “Pain” Is Ischemic in Origin on the Basis of Commonly Used Descriptors

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Gulati et al 2021 Chest Pain Guideline Executive Summary

Figure 3. Top 10 Causes of Chest Pain in the ED Based on Age (Weighted Percentage) Created using data from Hsia RY, et al.7 ED indicates emergency department.

2.1.2. Considerations for Older Patients With Chest Pain

2.1.3. Considerations for Diverse Patient Populations With Chest Pain

2.2. Physical Examination

Table 3 presents physical examination in patients with chest pain.

2.3. Diagnostic Testing

2.3.1. Setting Considerations

Recommendation for Considerations for Older Patients With Chest Pain

COR

LOE

Recommendation

C-LD

1. In patients with chest pain who are ≥75 years of age, ACS should be considered when accom- panying symptoms such as shortness of breath, syncope, or acute delirium are present, or when an unexplained fall has occurred.20

Recommendation for Physical Examination

COR

LOE

Recommendation

C-EO

1. In patients presenting with chest pain, a focused cardiovascular examination should be performed initially to aid in the diagnosis of ACS or other potentially serious causes of chest pain (eg, aortic dissection, pulmonary embolism (PE), or esopha- geal rupture) and to identify complications.

Recommendations for Considerations for Diverse Patient Populations With Chest Pain

COR

LOE

Recommendations

C-LD

1. Cultural competency training is recommended to help achieve the best outcomes in patients of diverse racial and ethnic backgrounds who pres- ent with chest pain.

C-LD

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

Recommendations for Setting Considerations

Referenced studies that support the recommendations are summarized in Online Data Supplement 5.

COR

LOE

Recommendations

B-NR

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.27-31

C-LD

2. Patients with clinical evidence of ACS or other life-threatening causes of acute chest pain seen in the office setting should be transported urgently to the ED, ideally by EMS.27-35

C-LD

3. In all patients who present with acute chest pain regardless of the setting, an ECG should be acquired and reviewed for ST-segment–eleva- tion myocardial infarction (STEMI) within 10 minutes of arrival.27-29,32,33,36

2.1.4. Patient-Centric Considerations

Recommendation for Patient-Centric Considerations

COR

LOE

Recommendation

C-LD

1. In patients with acute chest pain, it is recom- mended that 9-1-1 be activated by patients or bystanders to initiate transport to the closest ED by emergency medical services (EMS).21

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Table 3.

Physical Examination in Patients With Chest Pain

Diaphoresis, tachypnea, tachycardia, hypotension, crackles, S3, MR murmur22; examination may be nor- mal in uncomplicated cases

Tachycardia + dyspnea—>90% of patients; pain with inspiration23

Emesis, subcutaneous emphysema, pneumothorax (20% patients), unilateral decreased or absent breath sounds

Fever, pleuritic chest pain, increased in supine posi- tion, friction rub

Fever, chest pain, heart failure, S3

Epigastric tenderness

Right upper quadrant tenderness, Murphy sign

Fever, localized chest pain, may be pleuritic, friction rub may be present, regional dullness to percussion, egophony

Dyspnea and pain on inspiration, unilateral absence of breath sounds

Tenderness of costochondral joints

Pain in dermatomal distribution, triggered by touch; char- acteristic rash (unilateral and dermatomal distribution)

Recommendations for Setting Considerations (Continued)

COR

LOE

Recommendations

C-LD

4. In all patients presenting to the ED with

acute chest pain and suspected ACS, cTn should be measured as soon as possible after presentation.34,35

3: Harm

C-LD

5. For patients with acute chest pain and sus- pected ACS initially evaluated in the office setting, delayed transfer to the ED for

cTn or other diagnostic testing should be avoided.

Clinical Syndrome

Findings

Emergency

Aortic dissection

Connective tissue disorders (eg, Marfan syndrome), extremity pulse differential (30% of patients, type A>B)24 Severe pain, abrupt onset + pulse differential + widened mediastinum on CXR >80% probability of dissection25 Frequency of syncope >10%24, AR 40%–75% (type A)26

2.3.2. Electrocardiogram

Figure 4 presents electrocardiographic-directed man- agement of chest pain.

Table 2. Chest Pain Characteristics and Corresponding Causes

Nature

Anginal symptoms are perceived as retrosternal chest discomfort (eg, pain, discomfort, heaviness, tightness, pressure, constriction, squeezing) (See Section 1.4.2, Defining Chest Pain, in the full guideline1).

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 syn- drome.

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.

Physical exercise or emotional stress are common triggers of anginal symp- toms.

Occurrence at rest or with minimal exertion associated with anginal symp- toms 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.

Symptoms on the left or right side of the chest, stabbing, sharp pain, or discomfort in the throat or abdomen may occur in patients with diabetes, women, and elderly patients.

ACS indicates acute coronary syndrome.

ACS

Esophageal rupture

Pericarditis

Myocarditis

Esophagitis, peptic ulcer disease, gall bladder disease

Pneumonia

Pneumothorax

Costochondritis, Tietze syndrome

Herpes zoster

Other

Noncoronary car- diac: AS, AR, HCM

AS: Characteristic systolic murmur, tardus or parvus carotid pulse

AR: Diastolic murmur at right of sternum, rapid carotid upstroke

HCM: Increased or displaced left ventricular impulse, prominent a wave in jugular venous pressure, systolic murmur

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).

Precipitating factors

ACS indicates acute coronary syndrome; AR, aortic regurgitation; AS, aortic ste- nosis; CXR, chest x-ray; LR, likelihood ratio; HCM, hypertrophic cardiomyopathy; MR, mitral regurgitation; PE, pulmonary embolism; and PUD, peptic ulcer disease.

Recommendations for Electrocardiogram

Referenced studies that support the recommendations are summarized in Online Data Supplement 6.

COR

LOE

Recommendations

C-EO

1. In patients with chest pain in which an initial ECG is nondiagnostic, serial ECGs to detect potential ischemic changes should be per- formed, especially when clinical suspicion of ACS is high, symptoms are persistent, or the clinical condition deteriorates.33

C-EO

2. Patients with chest pain in whom the initial ECG is consistent with an ACS should be treated according to STEMI and non–ST-segment– elevation ACS guidelines.32,33

B-NR

3. In patients with chest pain and intermediate- to-high clinical suspicion for ACS in whom the initial ECG is nondiagnostic, supplemental elec- trocardiographic leads V7 to V9 are reasonable to rule out posterior myocardial infarction (MI).37-39

Associated symptoms

Common symptoms associated with myocardial ischemia include, but are not limited to, dyspnea, palpitations, diaphoresis, lightheadedness, presyn- cope or syncope, upper abdominal pain, or heartburn unrelated to meals and nausea or vomiting.

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2.3.3. Chest Radiography

2.3.4. Biomarkers

Figure 4. Electrocardiographic- Directed Management of Chest Pain

ECG indicates electrocardiogram; MI, myocardial infarction; NSTE-ACS, non– ST-segment–elevation acute coronary syndrome; and STEMI, ST-segment– elevation myocardial infarction.

3. CARDIAC TESTING GENERAL

CONSIDERATIONS

The approach outlined in this guideline focuses on selective use of testing, optimization of lower cost evalu- ations, reducing layered testing, and deferring or eliminat- ing testing when the diagnostic yield is low (Figure 5). Figure 6 display choosing the right diagnostic test. Table 4 presents contraindication by type of imaging modality.

4. CHOOSING THE RIGHT PATHWAY WITH

PATIENT-CENTRIC ALGORITHMS FOR

ACUTE CHEST PAIN

Figure 7 provides an overview of a patient-centric algo- rithm for acute chest pain.

4.1. Patients With Acute Chest Pain and Suspected Acute Coronary Syndrome (Not Including STEMI)

Recommendation for Chest Radiography

COR

LOE

Recommendation

C-EO

1. In patients presenting with acute chest pain,

a chest radiograph is useful to evaluate for other potential cardiac, pulmonary, and thoracic causes of symptoms.

Recommendations for Biomarkers

Referenced studies that support the recommendations are summarized in Online Data Supplement 7.

COR

LOE

Recommendations

B-NR

1. In patients presenting with acute chest pain, serial cTn I or T levels are useful to identify abnormal values and a rising or fall-

ing pattern indicative of acute myocardial injury.35,40-59

B-NR

2. In patients presenting with acute chest pain, high-sensitivity cTn is the preferred biomarker because it enables more rapid detection or exclusion of myocardial injury and increases diagnostic accuracy.35,56,60-63

C-EO

3. Clinicians should be familiar with the ana- lytical performance and the 99th percentile upper reference limit that defines myocar- dial injury for the cTn assay used at their institution.34,61

3: No benefit

B-NR

4. With availability of cTn, creatine kinase myo- cardial (CK-MB) isoenzyme and myoglobin are not useful for diagnosis of acute myocardial injury.64-69

Recommendations for Patients With Acute Chest Pain and Suspected ACS (Not Including STEMI)

Referenced studies that support the recommendations are summarized in Online Data Supplements 8 and 9.

COR

LOE

Recommendations

B-NR

1. In patients presenting with acute chest pain

and suspected ACS, clinical decision pathways (CDPs) should categorize patients into low-, inter- mediate-, and high-risk strata to facilitate disposi- tion and subsequent diagnostic evaluation.40-52,76

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Figure 5. Chest Pain and Cardiac Testing Considerations

The choice of imaging depends on the clinical question of importance, to either a) ascertain the diagnosis of CAD and define coronary anatomy or b) assess ischemia severity among patients with an expected higher likelihood of ischemia with an abnormal resting ECG or those incapable of performing maximal exercise.

ACS indicates acute coronary syndrome; CAC, coronary artery calcium; CAD, coronary artery disease; and ECG, electrocardiogram.

to estimate a patient’s probability of ACS or risk of 30- day major adverse cardiovascular events (MACE).90-95 The warranty period of prior cardiac testing should be considered, when symptoms are unchanged (Table 6). Low-risk chest pain has been defined in Table 7.

4.1.1. Low-Risk Patients With Acute Chest Pain

Recommendations for Patients With Acute Chest Pain and Suspected ACS (Not Including STEMI) (Continued)

COR

LOE

Recommendations

B-NR

2. In the evaluation of patients presenting with acute chest pain and suspected ACS for whom serial troponins are indicated to exclude myo- cardial 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.35,56,77

C-LD

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 tro- ponin sampling based on their particular assay.78,79

C-LD

B-NR

5. For patients with acute chest pain, a normal ECG, and symptoms suggestive of ACS that began at least 3 hours before ED arrival, a sin- gle hs-cTn concentration that is below the limit of detection on initial measurement (time zero) is reasonable to exclude myocardial injury.51,85-89

Recommendations for Low-Risk Patients With Acute Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplements 10 and 11.

COR

LOE

Recommendations

B-NR

1. Patients with acute chest pain and a 30-day

risk of death or major adverse cardiovascular

events (MACE) <1% should be designated as low risk.34,41,45,49,51,52,54,55,57,85,103

B-R

2. In patients with acute chest pain and suspected ACS who are deemed low-risk (<1% 30-day risk of death or MACE), it is reasonable to

discharge home without admission or urgent cardiac testing.60,94,97,104,105

4. In patients with acute chest pain and suspected ACS, previous testing when available should be considered and incorporated into CDPs.80-84

Patients with acute chest pain and suspected ACS cover a spectrum of disease likelihood and stratifica- tion into low- versus intermediate- or high-risk groups once STEMI has been excluded (Figure 8). Chest pain risk scores provide a summative assessment combining clinical information, such as age, ST-segment changes on ECG, symptoms, CAD risk factors, and cTn (Table 5)

4.1.2. Intermediate-Risk Patients With Acute Chest Pain

Recommendations for Intermediate-Risk Patients With Acute Chest Pain Referenced studies that support the recommendations are summarized in Online Data Supplements 12 and 13.

COR

LOE

Recommendations

C-EO

1. For intermediate-risk patients with acute chest pain, transthoracic echocardiography (TTE) is recommended as a rapid, bedside test to estab- lish baseline ventricular and valvular function, evaluate for wall motion abnormalities, and to assess for pericardial effusion.

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4.1.2.1. Intermediate-Risk Patients With Acute Chest Pain and No Known Coronary Artery Disease

Figure 9 presents an evaluation algorithm for pa- tients with suspected ACS at intermediate risk with no known CAD.

Figure 6. Choosing the Right Diagnostic Test

ASCVD indicates atherosclerotic cardiovascular disease; CAD, coronary artery disease; CAC, coronary artery calcium; CCTA, coronary computed tomography angiography; CMR, cardiovascular magnetic resonance; ETT, exercise tolerance test; LV, left ventricular; MPI, myocardial perfusion imaging; PET, positron emission tomography; and SPECT, single-photon emission computed tomography.

Recommendations for Intermediate-Risk Patients With Acute Chest Pain (Continued)

COR

LOE

Recommendations

2. For intermediate-risk patients with acute chest pain, management in an observation unit is rea- sonable to shorten length of stay and lower cost relative to an inpatient admission.106-112

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Gulati et al 2021 Chest Pain Guideline Executive Summary

Table 4. Contraindication by Type of Imaging Modality and Stress Protocol

Exercise ECG

Stress Nuclear70*

Stress Echocardiography71-73a

Stress CMR74

CCTA75*

Abnormal ST changes on resting ECG, digoxin, left bundle branch block, Wolff- Parkinson-White pattern, ven- tricular paced rhythm (unless test is performed to establish exercise capacity 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 arrhyth- mias (eg, VT, complete atrio- ventricular block) or high risk for arrhythmias caused by QT prolongation

Severe symptomatic aortic stenosis

Severe systemic arterial hypertension (eg, ≥200/110 mm Hg)

Acute illness (eg, acute PE, acute myocarditis/pericarditis, acute aortic dissection)

High-risk unstable angina, complicated ACS or AMI (<2 d)

Contraindications to vasodila- tor administration

Significant arrhythmias (eg, VT, second- or third-degree atrioventricular block) or sinus bradycardia <45 bpm

Significant hypotension (SBP <90 mm Hg)

Known or suspected bron- choconstrictive or broncho- spastic disease

Recent use of dipyridamole or dipyridamole-containing medications

Use of methylxanthines (eg, aminophylline, caffeine) within 12 h

Known hypersensitivity to adenosine, regadenoson

Severe systemic arterial hypertension (eg, ≥200/110 mm Hg)

Limited acoustic windows (eg, in COPD patients)

Inability to reach target heart rate

Uncontrolled heart failure

High-risk unstable angina, active ACS or AMI (<2 d)

Serious ventricular arrhythmia or high risk for arrhyth-

mias attributable to QT prolongation

Respiratory failure

Severe COPD, acute pulmo- nary emboli, severe pulmonary hypertension

Contraindications to dobuta- mine (if pharmacologic stress test needed)

Atrioventricular block, uncontrolled atrial fibrillation

Critical aortic stenosis†

Acute illness (eg, acute PE, acute myocarditis/ pericarditis, acute aortic dissection)

Hemodynamically sig- nificant LV outflow tract obstruction

Contraindications to atro- pine use:

Narrow-angle glaucoma

Myasthenia gravis

Obstructive uropathy

Obstructive gastrointesti- nal 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)

Reduced GFR (<30 mL/ min/1.73 m2)

Contraindications to vasodila- tor administration

Implanted devices not safe for CMR or producing arti- fact limiting scan quality/ interpretation

Significant claustrophobia

Caffeine use within past 12 h

Allergy to iodinated contrast

Inability to cooperate with scan acquisition and/or breath-hold instructions

Clinical instability (eg, acute myocardial infarction, decompensated heart failure, severe hypotension)

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 arrhythmia

Contraindication to nitroglycerin (if indicated)

For all the imaging modalities, inability to achieve high-quality images should be considered, in particular for obese patients

ACS indicates acute coronary syndrome; AMI, acute myocardial infarction; AS, aortic stenosis; CCTA, coronary computed tomography angiography; CMR, cardio- vascular magnetic resonance imaging; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; LV, left ventricular; MET, metabolic equivalent; MRI, magnetic resonance imaging; PE, pulmonary embolism; SBP, systolic blood pressure; and VT, ventricular tachycardia.

*Screening for potential pregnancy by history and/or pregnancy testing should be performed according to the local imaging facilities policies for undertaking radio- logical examinations that involve ionizing radiation in women of child-bearing age.

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

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Figure 7. Patient-Centric Algorithms for Acute Chest Pain

ECG indicates electrocardiogram; and STEMI, ST- segment–elevation myocardial infarction.

Recommendations for Intermediate-Risk Patients With No Known CAD Referenced studies that support the recommendations are summarized in Online Data Supplements 14 and 15.

COR

LOE

Recommendations

Index Diagnostic Testing

Anatomic Testing

1. For intermediate-risk patients with acute chest pain and no known CAD eligible for diagnostic testing after a negative or inconclusive evalu- ation for ACS, coronary computed tomography angiography (CCTA) is useful for exclusion

of atherosclerotic plaque and obstructive CAD.113-123

C-EO

2. For intermediate-risk patients with acute chest pain, moderate-severe ischemia on cur- rent or prior (≤1 year) stress testing, and no known CAD established by prior anatomic testing, invasive coronary angiography (ICA) is recommended.

C-LD

3. For intermediate-risk patients with acute chest pain with evidence of previous mildly abnormal stress test results (≤1 year), CCTA

is reasonable for diagnosing obstructive CAD.124,125

Stress Testing

B-NR

4. For intermediate-risk patients with acute chest pain and no known CAD who are eligible for cardiac testing, either exercise ECG, stress echocardiography, stress positron emission tomography (PET)/single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), or stress CMR

is useful for the diagnosis of myocardial ischemia.33,107,111,113,116,122,126-145

Recommendations for Intermediate-Risk Patients With No Known CAD (Continued)

COR

LOE

Recommendations

Sequential or Add-on Diagnostic Testing

B-NR

5. For intermediate-risk patients with acute chest pain and no known CAD, with a coronary artery stenosis of 40% to 90% in a proximal or middle coronary artery on CCTA, fractional flow reserve computed tomogra- phy (FFR-CT) can be useful for the diagnosis of ves- sel-specific ischemia and to guide decision-making regarding the use of coronary revascularization.146-152

C-EO

6. For intermediate-risk patients with acute chest pain and no known CAD, as well as an incon- clusive prior stress test, CCTA can be useful for excluding the presence of atherosclerotic plaque and obstructive CAD.

C-EO

7. For intermediate-risk patients with acute chest pain and no known CAD, with an inconclusive CCTA, stress imaging (with echocardiography, PET/SPECT MPI, or CMR) can be useful for the diagnosis of myocardial ischemia.

4.1.2.2. Intermediate-Risk Patients With Acute Chest Pain and Known Coronary Artery Disease

Recommendations for Intermediate-Risk Patients With Acute Chest Pain and Known CAD

Referenced studies that support the recommendations are summarized in Online Data Supplements 16 and 17.

COR

LOE

Recommendations

1. For intermediate-risk patients with acute chest pain who have known CAD and present with new onset or worsening symptoms, guideline-directed medical therapy (GDMT) should be optimized before additional cardiac testing is performed.153,154

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Figure 8. General Approach to

Risk Stratification of Patients With Suspected ACS

ACS indicates acute coronary syndrome; CDP, clinical decision pathway; and ECG, electrocardiogram.

4.1.3. High-Risk Patients With Acute Chest Pain

Recommendations for Intermediate-Risk Patients With Acute Chest Pain and Known CAD (Continued)

COR

LOE

Recommendations

2. For intermediate-risk patients with acute chest pain who have worsening frequency of symptoms with significant left main, proximal left anterior descending stenosis, or multivessel CAD on prior anatomic testing or history of prior coronary revas- cularization, ICA is recommended.113-115,119,155,156

B-NR

3. For intermediate-risk patients with acute chest pain and known nonobstructive CAD, CCTA can be useful to determine progression of athero- sclerotic plaque and obstructive CAD.157-159

B-NR

4. For intermediate-risk patients with acute chest pain and coronary artery stenosis of 40% to 90% in a proximal or middle segment on CCTA, FFR-CT is reasonable for diagnosis of vessel-specific isch- emia and to guide decision-making regarding the use of coronary revascularization.146,148,149,151,152,160

B-NR

5. For intermediate-risk patients with acute chest pain and known CAD who have new onset or worsening symptoms, stress imaging (PET/SPECT MPI, CMR, or stress echocardiography) is reasonable.120,126,129,142

Recommendations for High-Risk Patients With Acute Chest Pain

Referenced studies that support the recommendations are summarized in Online Data Supplements 18 and 19.

COR

LOE

Recommendations

Recommendations for High-Risk Patients, Including Those With High-Risk Findings on CCTA or Stress Testing

B-NR

1. For patients with acute chest pain and sus- pected ACS who have new ischemic changes on electrocardiography, troponin-confirmed acute myocardial injury, new-onset left ven- tricular systolic dysfunction (ejection fraction <40%), newly diagnosed moderate-severe ischemia on stress testing, hemodynamic instability, and/or a high CDP risk score should

be designated as high risk for short-term MACE.161-163

C-EO

B-NR

3. For high-risk patients with acute chest pain who are troponin positive in whom obstructive CAD has been excluded by CCTA or ICA, CMR or echocardiography can be effective in establishing alternative diagnoses.167-171

Figure 10 includes the evaluation algorithm for patients with known CAD, including patients with nonobstructive and obstructive CAD.

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2. For patients with acute chest pain and sus- pected ACS who are designated as high risk, ICA is recommended.33,164-166

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Table 5. Sample Clinical Decision Pathways Used to Define Risk

HEART Pathway91

EDACS96

ADAPT (mADAPT)97

NOTR94

2020 ESC/ hs-cTn*98,99

2016 ESC/ GRACE49,100

Target population

Suspected ACS

Suspected ACS, CP >5 min, planned se- rial troponin

Suspected ACS, CP >5 min, planned observation

Suspected ACS, ECG, troponin ordered

Suspected ACS, stable

Suspected ACS, planned serial troponin

Target outcome

↑ ED discharge without increasing missed 30-d or 1-y MACE

↑ ED discharge rate without in- creasing missed 30-d MACE

↑ ED discharge rate without increasing missed 30-d MACE

↑ Low-risk classification without increas- ing missed 30-d MACE

Early detection of AMI; 30-d MACE

Early detection of AMI

Patients with primary outcome in study popula- tion, %

Troponin

6–22

cTn, hs-cTn

12 15

hs-cTn cTn, hs-cTn

5–8 9.8

cTn, hs-cTn hs-cTn

10–17

cTn, hs-cTn

Variables used

History

ECG

Age

Risk factors Troponin (0, 3 h)

Age

Sex

Risk factors History Troponin (0, 2 h)

TIMI score 0-1

No ischemic ECG changes

Troponin (0, 2 h)

Age

Risk factors

Previous AMI or CAD

Troponin (0, 2 h)

History

ECG

hs-cTn (0, 1 or 2 h)

Age

HR, SBP

Serum Cr

Cardiac arrest ECG

Cardiac biomarker Killip class

Risk thresholds:

Low risk

HEART score ❤ Neg 0, 3-h cTn Neg 0, 2-h hs-cTn

EDACS score <16

Neg 0, 2 h hs-cTn

No ischemic ECG Δ

TIMI score 0 (or <1 for mADAPT)

Neg 0, 2-h cTn or hs-cTn

No ischemic ECG Δ

Age <50 y

❤ risk factors Previous AMI or CAD

Neg cTn or hs- cTn (0, 2 h)

Initial hs-cTn is “very low” and Sx onset >3 h ago

Initial hs-cTn “low” and 1– or 2-h hs-cTn Δ

is “low”

Chest pain free, GRACE <140

Sx <6 h – hs-cTn <ULN (0, 3 h)

Sx >6 h – hs-cTn <ULN (arrival)

Intermediate risk

HEART score 4-6

TIMI score 2-4

Initial hs-cTn is between “low” and “high”

And/Or

1- or 2-h hs-cTn Δ is between low and high thresholds

T0 hs-cTn = 12–52 ng/L or

1-h Δ = 3–5 ng/L

High risk

HEART score 7-10101,102

TIMI score 5-7102

Initial hs-cTn is “high”

1- or 2-h hs-cTn Δ is high

T0 hs-cTn >52 ng/L or Δ 1 h >5 ng/L

Performance

↑ ED discharges by 21% (40% versus 18%)

↓ 30-d objective testing by 12% (69% versus 57%)

↓ length of stay by 12 h (9.9 versus 21.9 h)

More patients identified as low risk versus ADAPT (42% versus 31%)

ADAPT: More dis- charged ≤6 h (19% versus 11%)

30-d MACE sen- sitivity =100%

28% eligible for ED discharge

AMI sensitivity >99%

62% Ruled out (0.2% 30-d MACE)

25% Observe 13% Rule in

AMI sensitivity >99%

30-d MACE not studied

AMI sensitivity, %

cTn accuracy: 30-d MACE sensitivity, %

hs-cTn accuracy: 30-d MACE sensitivity, %

ED discharge, %

100

95 40

100 100

92 93

49 19 (ADAPT) 39 (mADAPT)

100 >99

100 NA

99 99 28 —

96.7

— —

ACS indicates acute coronary syndrome; ADAPT, Accelerated Diagnostic protocol to Assess chest Pain using Troponins;

equivalent; Cr, creatinine; cTn, cardiac troponin; hs-cTn, high-sensitivity cardiac troponin; ECG, electrocardiogram; ED, emergency department; EDACS, emergency department ACS; ESC, European Society of Cardiology; GRACE, Global Registry of Acute Coronary Events; HEART, history, ECG, age, risk factors, troponin; HR, heart rate; hs, high sensi- tivity; MACE, major adverse cardiovascular events; mADAPT, modified (including TIMI scores of 1) ADAPT; NA, not applicable; neg, negative; NICE, National Institute for Health and Clinical Excellence; NOTR, No Objective Testing Rule; SBP, systolic blood pressure; SSACS, symptoms suggestive of ACS; Sx, symptoms; and ULN, upper limit of normal.

*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.98,99

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AMI, acute myocardial infarction; CP, chest pain or

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Table 6.

Anatomic

Table 7.

Pain

T-0

T-0 and 1- or 2-h Delta

Warranty Period for Prior Cardiac Testing

Definition Used for Low-Risk Patients With Chest

T-0 hs-cTn below the assay limit of detection or “very low” threshold if symptoms present for at least 3 h

T-0 hs-cTn and 1- or 2-h delta are both below the assay “low” thresholds (>99% NPV for 30-d MACE)

Test Modality

Result

Warranty Period

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

hs-cTn Based

Normal coronary angiogram CCTA with no stenosis or plaque

2 y

Stress testing

CCTA indicates coronary computed tomographic angiography.

4.1.4. Acute Chest Pain in Patients With Prior Coronary Artery Bypass Graft (CABG) Surgery

Normal stress test (given adequate stress)

1 y

Recommendations for Acute Chest Pain in Patients With Prior CABG Surgery

COR

LOE

Recommendations

C-LD

1. In patients with prior CABG surgery present- ing with acute chest pain who do not have ACS, performing stress imaging is effective to evaluate for myocardial ischemia or CCTA for graft stenosis or occlusion.172-178

C-LD

2. In patients with prior CABG surgery present- ing with acute chest pain, who do not have ACS165,179-184 or who have an indeterminate/ nondiagnostic stress test, ICA is useful.179

Clinical Decision Pathway Based

HEART Pathway91

EDACS105

ADAPT90

mADAPT

NOTR94

HEART score ≤3, initial and serial cTn/hs-cTn < assay 99th percentile

EDACS score ≤16; initial and serial cTn/hs-cTn < assay 99th percentile

TIMI score 0, initial and serial cTn/hs-cTn < assay 99th percentile

TIMI score 0/1, initial and serial cTn/hs-cTn < assay 99th percentile

0 factors

4.1.5. Evaluation of Patients With Acute Chest Pain Receiving Dialysis

1. In patients who experience acute unremitting chest pain while undergoing dialysis, transfer by EMS to an acute care setting is recommended.185-189

4.1.6. Evaluation of Acute Chest Pain in Patients With Cocaine and Methamphetamine Use

1. In patients presenting with acute chest pain, it is reasonable to consider cocaine and methamphet- amine use as a cause of their symptoms.190-192

4.1.7. Shared Decision-Making in Patients With Acute Chest Pain

ADAPT indicates 2-hour Accelerated Diagnostic Protocol to Access Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarkers; cTn, cardiac troponin; EDACS, Emergency Depart- ment 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 Acceler- ated Diagnostic Protocol to Access Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarkers; NOTR, No Objec- tive Testing Rule; NPV, negative predictive value; and TIMI, Thrombolysis in Myocardial Infarction.

4.2. Evaluation of Acute Chest Pain With Nonischemic Cardiac Pathologies

4.2.1. Acute Chest Pain With Suspected Acute Aortic Syndrome

Recommendation for Evaluation of Patients With Acute Chest Pain Receiving Dialysis

Referenced studies that support the recommendation are summarized in Online Data Supplement 20.

COR

LOE

Recommendation

B-NR

Recommendation for Evaluation of Acute Chest Pain With Nonischemic Cardiac Pathologies

COR

LOE

Recommendation

C-EO

1. In patients with acute chest pain in whom other potentially life-threatening nonischemic cardiac conditions are suspected (eg, aortic pathology, pericardial effusion, endocarditis), TTE is recom- mended for diagnosis.

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.

COR

LOE

Recommendation

B-NR

Recommendations for Shared Decision-Making in Patients With Acute Chest Pain

Referenced studies that support the recommendations are summarized in Online Data Supplement 22.

COR

LOE

Recommendations

B-R

1. For patients with acute chest pain and suspected ACS who are deemed low risk by a CDP, patient decision aids are beneficial to improve understand- ing and effectively facilitate risk communication.193,194

B-R

2. For patients with acute chest pain and suspected ACS who are deemed intermediate risk by a CDP, shared decision-making between the clinician and patient regarding the need for admission, for obser- vation, discharge, or further evaluation in an outpa- tient setting is recommended for improving patient understanding and reducing low-value testing.193,194

Recommendations for Acute Chest Pain With Suspected Acute Aortic Syndrome

COR

LOE

Recommendations

C-EO

1. In patients with acute chest pain where there is clinical concern for aortic dissec- tion, computed tomography angiography (CTA) of the chest, abdomen, and pelvis is recommended for diagnosis and treatment planning.

C-EO

2. In patients with acute chest pain where there is clinical concern for aortic dissec- tion, transesophageal echocardiography (TEE) or CMR should be performed to make the diagnosis if CT is contraindicated or unavailable.

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Figure 9. Evaluation Algorithm for Patients With Suspected ACS at Intermediate Risk With No Known CAD

Test choice should be guided by local availability and expertise.

*Recent negative test: normal CCTA ≤2 years (no plaque/no stenosis) OR negative stress test ≤1 year, given adequate stress. †High-risk CAD means left main stenosis ≥50%; anatomically significant 3-vessel disease (70% stenosis). ‡For FFR-CT, turnaround times may impact prompt clinical care decisions. However, the use of FFR-CT does not require additional testing, as would be the case when adding stress testing.

CAD indicates coronary artery disease; CCTA, coronary CT angiography; CMR, cardiovascular magnetic resonance imaging; CT, computed tomography; FFR-CT, fractional flow reserve with CT; GDMT, guideline-directed medical therapy; ICA, invasive coronary angiography; INOCA, ischemia and no obstructive coronary artery disease; PET, positron emission tomography; and SPECT, single-photon emission CT.

4.2.2. Acute Chest Pain With Suspected PE

1. In stable patients with acute chest pain with high clinical suspicion for PE, CTA using a PE protocol is recommended.195-198

2. For patients with acute chest pain and possible PE, need for further testing should be guided by pretest probability.

4.2.3. Acute Chest Pain With Suspected Myopericarditis

Recommendations for Acute Chest Pain With Suspected Myopericarditis (Continued)

COR

LOE

Recommendations

B-NR

2. In patients with acute chest pain with suspected acute myopericarditis, CMR is useful if there is diagnostic uncertainty, or to determine the pres- ence and extent of myocardial and pericardial inflammation and fibrosis.202-207

C-EO

3. In patients with acute chest pain and suspected myopericarditis, TTE is effective to determine the presence of ventricular wall motion abnor- malities, pericardial effusion, valvular abnormali- ties, or restrictive physiology.

C-LD

4. In patients with acute chest pain with suspected acute pericarditis, noncontrast or contrast cardiac CT scanning may be reasonable to determine the pres- ence and degree of pericardial thickening.202,203,208

Recommendations for Acute Chest Pain With Suspected PE Referenced studies that support the recommendations are summarized in Online Data Supplement 23.

COR

LOE

Recommendations

B-NR

C-EO

Recommendations for Acute Chest Pain With Suspected Myopericarditis Referenced studies that support the recommendations are summarized in Online Data Supplement 24.

COR

LOE

Recommendations

B-NR

1. In patients with acute chest pain and myocardial injury who have nonobstructive coronary arter- ies on anatomic testing, CMR with gadolinium contrast is effective to distinguish myopericar- ditis from other causes, including myocardial

infarction and nonobstructive coronary arteries (MINOCA).168,170,171,199-201

4.2.4. Acute Chest Pain With Valvular Heart Disease (VHD)

Recommendations for Acute Chest Pain With VHD

COR

LOE

Recommendations

C-EO

1. In patients presenting with acute chest pain with suspected or known history of VHD, TTE is useful in determining the presence, severity, and cause of VHD.

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Figure 10. Evaluation Algorithm for Patients With Suspected ACS at Intermediate Risk With Known CAD

Test choice should be guided by local availability and expertise.

*Known CAD is prior MI, revascularization, known obstructive or nonobstructive CAD on invasive or CCTA. †If extensive plaque is present a high-quality CCTA is unlikely to be achieved, and stress testing is preferred. ‡Obstructive CAD includes prior coronary artery bypass graft/ percutaneous coronary intervention. §High-risk CAD means left main stenosis ≥50%; anatomically significant 3-vessel disease (≥70% stenosis). ‖FFR-CT turnaround times may impact prompt clinical care decisions.

ACS indicates acute coronary syndrome; CAD, coronary artery disease; CCTA, coronary CT angiography; CMR, cardiovascular magnetic resonance; CT, computed tomography; FFR-CT, fractional flow reserve with CT; GDMT, guideline-directed medical therapy; ICA, invasive coronary angiography; INOCA, ischemia and no obstructive coronary artery disease; PET, positron emission tomography; and SPECT, single-photon emission CT.

4.3. Evaluation of Acute Chest Pain With Suspected Noncardiac Causes

Recommendations for Acute Chest Pain With VHD (Continued)

COR

LOE

Recommendations

C-EO

2. In patients presenting with acute chest pain with suspected or known VHD in whom TTE diagnostic quality is inadequate, TEE (with 3D imaging if available) is useful in determining the severity and cause of VHD.

C-EO

3. In patients presenting with acute chest pain with known or suspected VHD, CMR imaging is reasonable as an alternative to TTE and/or TEE is nondiagnostic.

Recommendation for Evaluation of Acute Chest Pain With Suspected Noncardiac Causes

COR

LOE

Recommendation

C-EO

1. Patients with acute chest pain should be evalu- ated for noncardiac causes if they have persis- tent or recurring symptoms despite a negative stress test or anatomic cardiac evaluation, or a low-risk designation by a CDP.

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Table 8. Differential Diagnosis of Noncardiac Chest Pain

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

The differential diagnosis for noncardiac causes of acute chest pain is quite broad, and includes respiratory, mus-

culoskeletal, gastrointestinal, psychological, and other causes (Table 8).

4.3.1. Evaluation of Acute Chest Pain With Suspected Gastrointestinal Syndromes

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

Recommendation for Evaluation of Acute Chest Pain With Suspected Gastrointestinal Syndromes

COR

LOE

Recommendation

C-LD

1. In patients with recurrent acute chest pain without evidence of a cardiac or pulmonary cause, evaluation for gastrointestinal causes is reasonable.

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

B-R

1. For patients with recurrent, similar presentations for acute chest pain with no evidence of a phys- iological cause on prior diagnostic evaluation including a negative workup for myocardial isch- emia, referral to a cognitive-behavioral therapist is reasonable.209-222

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

1. In patients with sickle cell disease who report acute chest pain, emergency transfer by EMS to an acute care setting is recommended.223-227

2. In patients with sickle cell disease who report acute chest pain, ACS should be excluded.225-227

5. EVALUATION OF PATIENTS WITH STABLE CHEST PAIN

5.1. Patients With No Known CAD Presenting

With Stable Chest Pain

Stable chest pain is a symptom of myocardial ischemia characterized by chest pain that is provoked with stress (physical or emotional). Risk status in stable ischemic heart disease (SIHD) is not well defined. Figure 11 pro- vides a description of SIHD risk estimates.228

Circulation. 2021;144:e336–e367. DOI: 10.1161/CIR.0000000000001030 November 30, 2021 e353

Recommendations for Evaluation of Acute Chest Pain in Patients With Sickle Cell Disease

Referenced studies that support the recommendations are summa- rized in Online Data Supplement 26.

COR

LOE

Recommendations

B-NR

C-LD

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5.1.2. Low-Risk Patients With Stable Chest Pain and No Known CAD

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

COR

LOE

Assessment of Left Ventricular Function

Recommendations

B-NR

6. In intermediate-high risk patients with stable chest pain who have pathological Q waves, symptoms or signs suggestive of heart failure, complex ventricu- lar arrhythmias, or a heart murmur with unclear diagnosis, use of TTE is effective for diagnosis

of resting left ventricular systolic and diastolic ventricular function and detection of myocardial, valvular, and pericardial abnormalities.249,250,285

Sequential or Add-on Testing: What to Do If Index Test Results Are Positive or Inconclusive

B-NR

7. For intermediate-high risk patients with stable chest pain and known coronary stenosis of 40% to 90% in a proximal or middle coronary seg- ment on CCTA, FFR-CT can be useful for diag- nosis of vessel-specific ischemia and to guide

decision-making regarding the use of coronary revascularization.146,148,149,160,286-288

B-NR

8. For intermediate-high risk patients with stable

chest pain after an inconclusive or abnormal

exercise ECG or stress imaging study, CCTA is reasonable.84,154,242,289-291

B-NR

C-EO

Recommendations for Low-Risk Patients With Stable Chest Pain and No Known CAD

Referenced studies that support the recommendations are summarized in Online Data Supplements 27 and 28.

COR

LOE

Recommendations

B-NR

1. For patients with stable chest pain and no known CAD presenting to the outpatient clinic, a model to estimate pretest probability of obstructive CAD is effective to identify patients at low risk for obstructive CAD and favorable prognosis in whom additional diagnostic testing can be deferred.228-232

B-R

2. For patients with stable chest pain and no known CAD categorized as low risk, CAC test- ing is reasonable as a first-line test for exclud- ing calcified plaque and identifying patients with a low likelihood of obstructive CAD.233-236

B-NR

3. For patients with stable chest pain and no known CAD categorized as low risk, exercise testing without imaging is reasonable as a first- line test for excluding myocardial ischemia and determining functional capacity in patients with an interpretable ECG.237

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

Figure 12 presents a CDP for patients with stable chest pain and no known CAD.

9. For intermediate-high risk patients with stable chest pain and no known CAD undergoing stress testing, the addition of CAC testing can be useful.235,292-297

10. For intermediate-high risk patients with stable

chest pain after inconclusive CCTA, stress imag- ing is reasonable.237,249,250,255-258,298-303

11. Forintermediate-highriskpatientswithstablechest pain after a negative stress test but with high clinical suspicion of CAD, CCTA or ICA may be reasonable.

5.2. Patients With Known CAD Presenting With Stable Chest Pain

1. For patients with obstructive CAD and stable chest pain, it is recommended to optimize GDMT.153,154,304

2. For patients with known nonobstructive CAD and stable chest pain, it is recommended to optimize preventive therapies.305,306

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

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

Referenced studies that support the recommendations are summarized in Online Data Supplements 29 and 30.

COR

LOE

Recommendations

Index Diagnostic Testing

Anatomic Testing

1. For intermediate-high risk patients with stable chest pain and no known CAD, CCTA is effec- tive for diagnosis of CAD, for risk stratification, and for guiding treatment decisions.160,238-248

Stress Testing

B-R

2. For intermediate-high risk patients with stable chest pain and no known CAD, stress imaging (stress echocardiography, PET/SPECT MPI or CMR) is effective for diagnosis of myocardial isch- emia and for estimating risk of MACE.124,245,249-270

B-R

3. For intermediate-high risk patients with stable chest pain and no known CAD for whom rest/ stress nuclear MPI is selected, PET is reason- able in preference to SPECT, if available to improve diagnostic accuracy and decrease the rate of nondiagnostic test results.271-274

B-R

4. For intermediate-high risk patients with stable chest pain and no known CAD with an inter- pretable ECG and ability to achieve maximal levels of exercise (≥5 metabolic equivalent

[MET]s), exercise electrocardiography is reasonable.181,237,245,249,251,275-278

B-NR

5. In intermediate-high risk patients with stable chest pain selected for stress MPI using SPECT, the use of attenuation correction or prone imag- ing may be reasonable to decrease the rate of false-positive findings.279-284

Recommendations for Patients With Known CAD Presenting With Stable Chest Pain

Referenced studies that support the recommendations are summarized in Online Data Supplement 31.

COR

LOE

Recommendations

C-EO

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.

COR

LOE

Recommendations

Index Diagnostic Testing

Anatomic Testing

1. For patients with obstructive CAD who have stable chest pain despite GDMT and moderate- severe ischemia, ICA is recommended for guid- ing therapeutic decision-making.153,154,304,307

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Figure 11. Pretest Probabilities of Obstructive CAD in Symptomatic Patients According to Age, Sex, and Symptoms

Modified from Juarez-Orozco et al228 and Winther S et al.229 1) The pretest probability shown is for patients with anginal symptoms. Patients with lower-risk symptoms would be expected to have lower pretest probability.

2) The darker green– and orange-shaded regions denote the groups in which noninvasive testing is most beneficial (pretest probability >15%). The light green–shaded regions denote the groups with pretest probability of CAD ≤15% in which the testing for diagnosis may be considered based on clinical judgment.228 3) If CAC is available,

it can also be used to estimate the pretest probability based on CAC score.229 CAC indicates coronary artery calcium; and CAD, coronary artery disease.

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

COR

LOE

Recommendations

Anatomic Testing (continued)

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.307-310

B-R

3. For symptomatic patients with obstructive CAD who have stable chest pain with CCTA-defined ≥50% stenosis in the left main coronary artery, obstructive CAD with FFR with CT ≤0.80, or severe stenosis (≥70%) in all 3 main vessels, ICA is effec- tive for guiding therapeutic decision-making.154,165

B-NR

4. For patients who have stable chest pain with previous coronary revascularization, CCTA is reasonable to evaluate bypass graft or stent patency (for stents ≥3 mm).288,311-314

Stress Testing

B-NR

5. For patients with obstructive CAD who have stable chest pain despite optimal GDMT, stress PET/SPECT MPI, CMR, or echocardiography is recommended for diagnosis of myocardial ischemia, estimating risk of MACE, and guiding therapeutic decision-making.265,272,315-335

B-R

6. For patients with obstructive CAD who have stable chest pain despite optimal GDMT, when selected for rest/stress nuclear MPI, PET is reasonable in preference to SPECT, if available, to improve diagnostic accuracy and decrease the rate of nondiagnostic test results.261

B-NR

7. For patients with obstructive CAD who have stable chest pain despite GDMT, exercise treadmill test-

ing can be useful to determine if the symptoms are consistent with angina pectoris, assess the severity of symptoms, evaluate functional capacity and select management, including cardiac rehabilitation.154,336-338

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

COR

LOE

Recommendations

Stress Testing (continued)

B-NR

8. For patients with obstructive CAD who have stable chest pain symptoms undergoing stress PET MPI or stress CMR, the addition of myocardial blood flow reserve is useful to improve diagnosis accuracy and enhance risk stratification.272,331-335

Imaging should be considered in those with new onset or persistent stable chest pain (Figure 13).

5.2.1.1. Patients With Prior CABG Surgery With Stable Chest Pain

Recommendations for Patients With Prior CABG Surgery With Stable Chest Pain

COR

LOE

Recommendations

C-LD

1. In patients who have had prior CABG sur- gery presenting with stable chest pain

whose noninvasive stress test results show moderate-to-severe ischemia,165,179-184 or in those suspected to have myocardial ischemia with indeterminate/nondiagnostic stress test, ICA is recommended for guiding therapeutic decision-making.179

C-LD

2. In patients who have had prior CABG surgery presenting with stable chest pain who are suspected to have myocardial ischemia, it is reasonable to perform stress imaging or CCTA to evaluate for myocardial ischemia or graft ste- nosis or occlusion.172-178,339

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Gulati et al 2021 Chest Pain Guideline Executive Summary

Figure 12. Clinical Decision Pathway for Patients With Stable Chest Pain and No Known CAD

Test choice should be guided by local availability and expertise.

*Test choice guided by patient’s exercise capacity, resting electrocardiographic abnormalities; CCTA preferable in those <65 years of age and not on optimal preventive therapies; stress testing favored in those ≥65 years of age (with a higher likelihood of ischemia). †High-risk CAD means left main stenosis ≥50%; anatomically significant 3-vessel disease (≥70% stenosis).

CAD indicates coronary artery disease; CCTA, coronary CT angiography; CMR, cardiovascular magnetic resonance imaging; CT, computed tomography; FFR-CT, fractional flow reserve with CT; GDMT, guideline-directed medical therapy; INOCA, ischemia and no obstructive CAD; PET, positron emission tomography; and SPECT, single-photon emission CT.

Recommendations for Patients With Known Nonobstructive CAD Presenting With Stable Chest Pain (Continued)

COR

Anatomic Testing (continued)

LOE

Recommendations

B-NR

Stress Testing

C-LD

3. For patients with known extensive nonobstruc- tive CAD with stable chest pain symptoms, stress imaging (PET/SPECT, CMR, or echocar-

diography) is reasonable for the diagnosis of myocardial ischemia.272,328,331-334,344-347

5.2.2. Patients With Known Nonobstructive CAD Presenting With Stable Chest Pain

Recommendations for Patients With Known Nonobstructive CAD Presenting With Stable Chest Pain

Referenced studies that support the recommendations are summarized in Online Data Supplements 34 and 35.

COR

LOE

Recommendations

Index Diagnostic Testing

Anatomic Testing

B-NR

1. For symptomatic patients with known nonobstruc- tive CAD who have stable chest pain, CCTA is reasonable for determining atherosclerotic plaque burden and progression to obstructive CAD, and guiding therapeutic decision-making.124,158,159,340-343

2. For patients with known coronary stenosis from 40% to 90% on CCTA, FFR can be useful for diagnosis of vessel-specific ischemia and to guide decision- making regarding the use of ICA.146,148,149,160,286-288

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Figure 13. Clinical Decision Pathway for Patients With Stable Chest Pain (or Equivalent) Symptoms With Prior MI, Prior Revascularization, or Known CAD on Invasive Coronary Angiography or CCTA, Including Those With Nonobstructive CAD

Test choice should be guided by local availability and expertise.

*Known CAD means prior MI, revascularization, known obstructive CAD, nonobstructive CAD. †High-risk CAD means left main stenosis ≥50%; or obstructive CAD with FFR-CT ≤0.80. ‡Test choice guided by the patient’s exercise capacity, resting electrocardiographic abnormalities. §Patients with prior CABG or stents >3.0 mm. Follow-up Testing and Intensification of GDMT Guided by Initial Test Results and Persistence / Worsening / Frequency of Symptoms and Shared Decision Making.

CABG indicates coronary artery bypass graft; CAD, coronary artery disease; CCTA, coronary CT angiography; CMR, cardiovascular magnetic resonance imaging; CT, computed tomography; ECG, electrocardiogram; FFR-CT, fractional flow reserve with CT; GDMT, guideline-directed medical therapy; ICA, invasive coronary angiography; iFR, instant wave-free ratio; INOCA, ischemia and no obstructive coronary artery disease; MI, myocardial infarction; MPI, myocardial perfusion imaging; PET, positron emission tomography; SIHD, stable ischemic heart disease; and SPECT, single-photon emission CT.

5.2.3. Patients With Suspected Ischemia and No Obstructive CAD (INOCA)

Recommendations for Patients With Suspected INOCA (Continued)

COR

LOE

Recommendations

B-NR

2. For patients with persistent stable chest pain and nonobstructive CAD, stress PET MPI with myocardial blood flow reserve is reasonable to diagnose microvascular dysfunction and enhance risk stratification.272,331-334,344,345

B-NR

3. For patients with persistent stable chest pain and nonobstructive CAD, stress CMR with the addition of myocardial blood flow reserve measurement is rea- sonable to improve diagnosis of coronary myocardial dysfunction and for estimating risk of MACE.328,346,347

Recommendations for Patients With Suspected INOCA Referenced studies that support the recommendations are summarized in Online Data Supplements 36 and 37.

COR

LOE

Recommendations

B-NR

1. For patients with persistent stable chest pain and nonobstructive CAD and at least mild myocardial ischemia on imaging, it is reasonable to consider invasive coronary function testing to improve the diagnosis of coronary microvascular dysfunction and to enhance risk stratification.348-351

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Gulati et al 2021 Chest Pain Guideline Executive Summary

Figure 14. Clinical Decision Pathway for INOCA

Test choice should be guided by local availability and expertise.

*Ford T et al.352 †Cannot exclude microvascular vasospasm.

ACh indicates acetylcholine; CAD, coronary artery disease; CFR, coronary flow reserve; CFVR, coronary flow velocity reserve; CMD, coronary microvascular dysfunction; CV, cardiovascular; ECG, electrocardiographic; FFR, fractional flow reserve; GDMT, guideline-directed medical therapy; IMR, index of microcirculatory restriction; INOCA, ischemia and no obstructive CAD; MACE, major adverse cardiovascular events; and MBFR, myocardial blood flow reserve.

Recommendations for Patients With Suspected INOCA (Continued)

COR

LOE

Recommendations

C-EO

4. For patients with persistent stable chest pain and nonobstructive CAD, stress echocardiogra- phy with the addition of coronary flow velocity reserve measurement may be reasonable to improve diagnosis of coronary myocardial dys- function and for estimating risk of MACE.

A proposed diagnostic evaluation pathway is outlined in Figure 14.

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. Arm- bruster, 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, 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. Wi- jeysundera, MD, PhD*; Y. Joseph Woo, MD, FAHA, FACC

*Former ACC/AHA Joint Committee member; current member during the writing effort.

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ARTICLE INFORMATION

This document was approved by the American College of Cardiology Clinical Pol- icy Approval Committee in May 2021, the American Heart Association Science Advisory and Coordinating Committee in May 2021, the Society of Cardiovascu- lar 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 Ameri- can Society of Echocardiography in June 2021, the American Heart Association Executive Committee in July 2021, and the American College of Cardiology Sci- ence and Quality Committee in July 2021.

Supplemental materials are available with this article at https://www.ahajour- nals.org/doi/suppl/10.1161/CIR.0000000000001030.

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/ statements by selecting the “Guidelines & Statements” button. To purchase addi- tional 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 “Guide- lines & 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 Re- quest Form” appears in the second paragraph (https://www.heart.org/en/about- us/statements-and-policies/copyright-request-form).

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