Evaluation and Diagnosis of Chest Pain

Publication Date: October 27, 2021
Last Updated: October 30, 2024

Key Points

Key Points

Scope of the Problem

Synopsis

  • After injuries, chest pain is the second most common 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.
  • Chest pain also leads to nearly 4 million outpatient visits annually in the United States.
  • 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.
    • 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%, and women experience this symptom more often than men.
    • 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.
    • Nonetheless, chest pain is the most common symptom of CAD in both men and women.

Top 10 Take-Home Messages:*

  1. 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.
  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 accurate 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 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 evidence-based diagnostic protocols.
* Figure 1 illustrates the take-home messages.

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

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

Treatment

Treatment

1.4.2. Defining Chest Pain

  1. An initial assessment of chest pain is recommended to triage patients effectively on the basis of the likelihood that symptoms may be attributable to myocardial ischemia.
(I, B-NR)
573
  1. 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.
(I, C-LD)
573

2. Initial Evaluation

2.1 Recommendation for History

  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 factor assessment should be obtained..
(I, C-LD)
573

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

Figure 3. Top 10 Causes of Chest Pain in the ED Based on Age (Weighted Percentage)

Created using data from Hsia RY, et al. Intern Med.2016;176:1029-32.
Note: The numbering of the following tables and figures differs from that of the Clinical Practice Guideline.

Table 1. Chest Pain Characteristics and Corresponding Causes

Having trouble viewing table?
Nature
  • Anginal symptoms are perceived as retrosternal chest discomfort (e.g., pain, discomfort, heaviness, tightness, pressure, constriction, squeezing) (Section 1.4.2, Defining Chest Pain).
  • Sharp chest pain that increases with inspiration and lying supine is unlikely related to ischemic heart disease (e.g., 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 (e.g., aortic dissection).
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 (e.g., musculoskeletal).
Relieving factors
  • Relief with nitroglycerin is not necessarily diagnostic of myocardial ischemia and should not be used as a diagnostic criterion.
Associated symptoms
  • Common symptoms associated with myocardial ischemia include, but are not limited to, dyspnea, palpitations, diaphoresis, lightheadedness, presyncope or syncope, upper abdominal pain, or heartburn unrelated to meals and nausea or vomiting.
  • 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.

2.1.1. 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.
(I, B-NR)
573
  1. In women presenting with chest pain, it is recommended to obtain a history that emphasizes accompanying symptoms that are more common in women with ACS.
(I, B-NR)
573

2.1.2. Considerations for Older Patients With Chest Pain

  1. In patients with chest pain who are >75 years of age, ACS should be considered when accompanying symptoms such as shortness of breath, syncope, or acute delirium are present, or when an unexplained fall has occurred.
(I, C-LD)
573

2.1.3. Considerations for Diverse Patient Populations With Chest Pain

  1. Cultural competency training is recommended to help achieve the best outcomes in patients of diverse racial and ethnic backgrounds who present with chest pain.
(I, C-LD)
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  1. 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.
(I, C-LD)
573

2.1.4. Patient-Centric Considerations

  1. In patients with acute chest pain, it is recommended that 9-1-1 be activated by patients or bystanders to initiate transport to the closest ED by emergency medical services (EMS).
(I, C-LD)
573

2.2. Physical Examination

  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 (e.g., aortic dissection, PE, or esophageal rupture) and to identify complications.
(I, C-EO)
573
Table 2. Physical Examination in Patients With Chest Pain
Having trouble viewing table?
Clinical Syndrome Findings
Emergency
ACS
  • Diaphoresis, tachypnea, tachycardia, hypotension, crackles, S3, MR murmur; examination may be normal in uncomplicated cases
PE
  • Tachycardia + dyspnea—>90% of patients; pain with inspiration
Aortic dissection
  • Connective tissue disorders (e.g., Marfan syndrome), extremity pulse differential (30% of patients, type A>B)
  • Severe pain, abrupt onset + pulse differential + widened mediastinum on CXR >80% probability of dissection
  • Frequency of syncope >10%, AR 40%–75% (type A)
Esophageal rupture
  • Emesis, subcutaneous emphysema, pneumothorax (20% patients), unilateral decreased or absent breath sounds
Other
Noncoronary cardiac: 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
Pericarditis

Myocarditis
  • Fever, pleuritic chest pain, increased in supine position, friction rub
  • Fever, chest pain, heart failure, S3
Esophagitis, peptic ulcer disease, gall bladder disease
  • Epigastric tenderness
  • Right upper quadrant tenderness, Murphy sign
Pneumonia
  • Fever, localized chest pain, may be pleuritic, friction rub may be present, regional dullness to percussion, egophony
Pneumothorax
  • Dyspnea and pain on inspiration, unilateral absence of breath sounds
Costochondritis, Tietze syndrome
  • Tenderness of costochondral joints
Herpes zoster
  • Pain in dermatomal distribution, triggered by touch; characteristic rash (unilateral and dermatomal distribution)

2.3. Diagnostic Testing

2.3.1. Setting Considerations

  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.
(I, B-NR)
573
  1. 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.
(I, C-LD)
573
  1. In all patients who present with acute chest pain regardless of the setting, an ECG should be acquired and reviewed for STEMI within 10 minutes of arrival.
(I, C-LD)
573
  1. In all patients presenting to the ED with acute chest pain and suspected ACS, cTn should be measured as soon as possible after presentation.
(I, C-LD)
573
  1. For patients with acute chest pain and suspected ACS initially evaluated in the office setting, delayed transfer to the ED for cTn or other diagnostic testing should be avoided.
(III - Harm, C-LD)
573

2.3.2. Electrocardiogram (ECG)

  1. In patients with chest pain in which an initial ECG is nondiagnostic, serial ECGs to detect potential ischemic changes should be performed, especially when clinical suspicion of ACS is high, symptoms are persistent, or the clinical condition deteriorates.
(I, C-EO)
573
  1. Patients with chest pain in whom the initial ECG is consistent with an ACS should be treated according to STEMI and NSTE-ACS guidelines.
(I, C-EO)
573
  1. In patients with chest pain and intermediate-to-high clinical suspicion for ACS in whom the initial ECG is nondiagnostic, supplemental electrocardiographic leads V7 to V9 are reasonable to rule out posterior MI.
(IIa, B-NR)
573

Figure 4. Electrocardiographic-Directed Management of Chest Pain

2.3.3. Chest Radiography

  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.
(I, C-EO)
573

2.3.4. Biomarkers

  1. In patients presenting with acute chest pain, serial cTn I or T levels are useful to identify abnormal values and a rising or falling pattern indicative of acute myocardial injury.
(I, B-NR)
573
  1. 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.
(I, B-NR)
573
  1. 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.
(I, C-EO)
573
  1. With availability of cTn, creatine kinase myocardial (CK-MB) isoenzyme and myoglobin are not useful for diagnosis of acute myocardial injury.
(III - No Benefit, B-NR)
573

Figure 5. Chest Pain and Cardiac Testing Considerations

Figure 6. Choosing the Right Diagnostic Test

Table 3. Contraindication by Type of Imaging Modality and Stress Protocol

Having trouble viewing table?
aExercise ECG Stress Nucleara
  • Abnormal ST changes on resting ECG, digoxin, left bundle branch block, Wolff-Parkinson-White pattern, ventricular 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) i.e., active ACS
  • Uncontrolled heart failure
  • Significant cardiac arrhythmias (e.g., VT, complete atrioventricular block) or high risk for arrhythmias caused by QT prolongation
  • Severe symptomatic aortic stenosis
  • Severe systemic arterial hypertension (e.g., ≥200/110 mm Hg)
  • Acute illness (e.g., acute PE, acute myocarditis/pericarditis, acute aortic dissection)
  • High-risk unstable angina, complicated ACS or AMI (<2 d)
  • Contraindications to vasodilator administration
    • Significant arrhythmias (e.g., VT, second- or third-degree atrioventricular block) or sinus bradycardia <45 bpm
    • Significant hypotension (SBP <90 mm Hg)
    • Known or suspected bronchoconstrictive or bronchospastic disease
    • Recent use of dipyridamole or dipyridamole-containing medications
    • Use of methylxanthines (e.g., aminophylline, caffeine) within 12 hours
    • Known hypersensitivity to adenosine, regadenoson
  • Severe systemic arterial hypertension (e.g., ≥200/110 mm Hg)
Stress Echocardiography Stress CMR CCTAa
  • Limited acoustic windows (e.g., 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 arrhythmias attributable to QT prolongation
  • Respiratory failure
  • Severe COPD, acute pulmonary emboli, severe pulmonary hypertension
  • Contraindications to dobutamine (if pharmacologic stress test needed)
    • atrioventricular block, uncontrolled atrial fibrillation
    • Critical aortic stenosisb
    • Acute illness (e.g., acute PE, acute myocarditis/pericarditis, acute aortic dissection)
    • Hemodynamically significant LV outflow tract obstruction
    • Contraindications to atropine use:
      • Narrow-angle glaucoma
      • Myasthenia gravis
      • Obstructive uropathy
      • Obstructive gastrointestinal disorders
      • Severe systemic arterial hypertension (e.g., ≥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 vasodilator administration
  • Implanted devices not safe for CMR or producing artifact limiting scan quality/interpretation
  • Significant claustrophobia
  • Caffeine use within last 12 h
  • Allergy to iodinated contrast
  • Inability to cooperate with scan acquisition and/or breath-hold instructions;
  • Clinical instability (e.g. acute respiratory distress, severe hypotension, unstable arrhythmia);
  • 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.

a 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.

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

Figure 7. Patient-Centric Algorithms for Acute Chest Pain

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

  1. In patients presenting with acute chest pain and suspected ACS, clinical decision pathways (CDPs) should categorize patients into low-, intermediate-, and high-risk strata to facilitate disposition and subsequent diagnostic evaluation.
(I, B-NR)
573
  1. 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.
(I, B-NR)
573
  1. 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.
(I, C-LD)
573
  1. In patients with acute chest pain and suspected ACS, previous testing when available should be considered and incorporated into CDPs.
(I, C-LD)
573
  1. For patients with acute chest pain, a normal ECG, and symptoms suggestive of ACS that began at least 3 hours before ED arrival, a single hs-cTn concentration that is below the limit of detection on initial measurement (time zero) is reasonable to exclude myocardial injury.
(IIa, B-NR)
573

Figure 8. General Approach to Risk Stratification of Patients With Suspected ACS

Table 4. Warranty Period for Prior Cardiac Testing

Having trouble viewing table?
Test Modality Result Warranty Period
Anatomic
  • Normal coronary angiogram
  • CCTA with no stenosis or plaque
 2 y
Stress testing
  • Normal stress test (given adequate stress)
 1 y

4.1.1. Low-Risk Patients With Acute Chest Pain

  1. Patients with acute chest pain and a 30-day risk of death or MACE <1% should be designated as low risk.
(I, B-NR)
573
  1. 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.
(IIa, B-R)
573
Table 5. Definition Used for Low-Risk Patients With Chest Pain
Having trouble viewing table?
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
HEART Pathway HEART score <3, initial and serial cTn/hs-cTn < assay 99th percentile
EDACS EDACS <16; initial and serial cTn/hs-cTn < assay 99th percentile
ADAPT TIMI score 0, initial and serial cTn/hs-cTn < assay 99th percentile
mADAPT TIMI score 0/1, initial and serial cTn/hs-cTn < assay 99th percentile
NOTR 0 factors

4.1.2. Intermediate-Risk Patients With Acute Chest Pain

  1. For intermediate-risk patients with acute chest pain, TTE is recommended as a rapid, bedside test to establish baseline ventricular and valvular function, evaluate for wall motion abnormalities, and to assess for pericardial effusion.
(I, C-EO)
573
  1. For intermediate-risk patients with acute chest pain, management in an observation unit is reasonable to shorten length of stay and lower cost relative to an inpatient admission.
(IIa, A)
573

4.1.2.1. Intermediate-Risk Patients With No Known (CAD)

Anatomic Testing
  1. For intermediate-risk patients with acute chest pain and no known CAD eligible for diagnostic testing after a negative or inconclusive evaluation for ACS, CCTA is useful for exclusion of atherosclerotic plaque and obstructive CAD.
(I, A)
573
  1. For intermediate-risk patients with acute chest pain, moderate-severe ischemia on current or prior (≤1 year) stress testing, and no known CAD established by prior anatomic testing, ICA is recommended.
(I, C-EO)
573
  1. 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.
(IIa, C-LD)
573
Stress Testing
  1. For intermediate-risk patients with acute chest pain and no known CAD who are eligible for cardiac testing, either exercise ECG, stress echocardiography, stress PET/SPECT MPI, or stress CMR is useful for the diagnosis of myocardial ischemia.
(I, B-NR)
573
Sequential or Add-on Diagnostic Testing
  1. 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, FFR-CT can be useful for the diagnosis of vessel-specific ischemia and to guide decision-making regarding the use of coronary revascularization.
(IIa, B-NR)
573
  1. For intermediate-risk patients with acute chest pain and no known CAD, as well as an inconclusive prior stress test, CCTA can be useful for excluding the presence of atherosclerotic plaque and obstructive CAD.
(IIa, C-EO)
573
  1. 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.
(IIa, C-EO)
573

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

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

  1. For intermediate-risk patients with acute chest pain who have known CAD and present with new onset or worsening symptoms, GDMT should be optimized before additional cardiac testing is performed.
(I, A)
573
  1. 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 revascularization, ICA is recommended.
(I, A)
573
  1. For intermediate-risk patients with acute chest pain and known nonobstructive CAD, CCTA can be useful to determine progression of atherosclerotic plaque and obstructive CAD.
(IIa, B-NR)
573
  1. 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 ischemia and to guide decision-making regarding the use of coronary revascularization.
(IIa, B-NR)
573
  1. 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.
(IIa, B-NR)
573

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

4.1.3. High-Risk Patients With Acute Chest Pain

  1. For patients with acute chest pain and suspected ACS who have new ischemic changes on electrocardiography, troponin-confirmed acute myocardial injury, new-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.
(I, B-NR)
573
  1. For patients with acute chest pain and suspected ACS who are designated as high risk, ICA is recommended.
(I, C-EO)
573
  1. 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.
(IIa, B-NR)
573

4.1.4. Acute Chest Pain in Patients With Prior CABG Surgery

  1. In patients with prior CABG surgery presenting 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.
(I, C-LD)
573
  1. In patients with prior CABG surgery presenting with acute chest pain, who do not have ACS or who have an indeterminate/nondiagnostic stress test, ICA is useful.
(I, C-LD)
573

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.
(I, B-NR)
573

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 methamphetamine use as a cause of their symptoms.
(IIa, B-NR)
573

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

  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 understanding and effectively facilitate risk communication.
(I, B-R)
573
  1. 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 observation, discharge, or further evaluation in an outpatient setting is recommended for improving patient understanding and reducing low-value testing.
(I, B-R)
573

4.2. Evaluation of Acute Chest Pain With Nonischemic Cardiac Pathologies

  1. In patients with acute chest pain in whom other potentially life-threatening nonischemic cardiac conditions are suspected (e.g., aortic pathology, pericardial effusion, endocarditis), TTE is recommended for diagnosis.
(I, C-EO)
573

4.2.1. Acute Chest Pain With Suspected Acute Aortic Syndrome

  1. In patients with acute chest pain where there is clinical concern for aortic dissection, computed tomography angiography (CTA) of the chest, abdomen, and pelvis is recommended for diagnosis and treatment planning.
(I, C-EO)
573
  1. In patients with acute chest pain where there is clinical concern for aortic dissection, TEE or CMR should be performed to make the diagnosis if CT is contraindicated or unavailable.
(I, C-EO)
573

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.
(I, B-NR)
573
  1. For patients with acute chest pain and possible PE, need for further testing should be guided by pretest probability.
(I, C-EO)
573

4.2.3. Acute Chest Pain With Suspected Myopericarditis

  1. In patients with acute chest pain and myocardial injury who have nonobstructive coronary arteries on anatomic testing, CMR with gadolinium contrast is effective to distinguish myopericarditis from other causes, including myocardial infarction and nonobstructive coronary arteries (MINOCA).
(I, B-NR)
573
  1. In patients with acute chest pain with suspected acute myopericarditis, CMR is useful if there is diagnostic uncertainty, or to determine the presence and extent of myocardial and pericardial inflammation and fibrosis.
(I, B-NR)
573
  1. In patients with acute chest pain and suspected myopericarditis, TTE is effective to determine the presence of ventricular wall motion abnormalities, pericardial effusion, valvular abnormalities, or restrictive physiology.
(I, C-EO)
573
  1. In patients with acute chest pain with suspected acute pericarditis, non-contrast or contrast cardiac CT scanning may be reasonable to determine the presence and degree of pericardial thickening.
(IIb, C-LD)
573

4.2.4. Acute Chest Pain With Valvular Heart Disease

  1. In patients presenting with acute chest pain with suspected or known history of valvular heart disease (VHD), TTE is useful in determining the presence, severity, and cause of VHD.
(I, C-EO)
573
  1. 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.
(I, C-EO)
573
  1. 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.
(IIa, C-EO)
573

4.3 Evaluation of Acute Chest Pain With Suspected Noncardiac Causes

  1. Patients with acute chest pain should be evaluated for noncardiac causes if they have persistent or recurring symptoms despite a negative stress test or anatomic cardiac evaluation, or a low-risk designation by a CDP.
(I, C-EO)
573

Table 6. Differential Diagnosis of Noncardiac Chest Pain

Having trouble viewing table?
Respiratory Pulmonary embolism Bronchitis
Pneumothorax/hemothorax Pleural irritation
Pneumomediastinum Malignancy
Pneumonia
Gastrointestinal Cholecystitis Peptic ulcer disease
Pancreatitis Esophageal spasm
Hiatal hernia Dyspepsia
Gastroesophageal reflux disease/gastritis/esophagitis
Chest wall Costochondritis Breast disease
Chest wall trauma or inflammation Rib fracture
Herpes zoster (shingles) Musculoskeletal injury/spasm
Cervical radiculopathy
Psychological Panic disorder Somatization disorder
Anxiety Hypochondria
Clinical depression
Other Hyperventilation syndrome Prolapsed intervertebral disc
Carbon monoxide poisoning Thoracic outlet syndrome
Sarcoidosis Adverse effect of certain medications (e.g., 5-fluorouracil)
Lead poisoning Sickle cell crisis

4.3.1. Evaluation of Acute Chest Pain With Suspected Gastrointestinal Syndromes

  1. In patients with recurrent acute chest pain without evidence of a cardiac or pulmonary cause, evaluation for gastrointestinal causes is reasonable.
(IIa, C-LD)
573

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

  1. For patients with recurrent, similar presentations for acute chest pain with no evidence of a physiological cause on prior diagnostic evaluation including a negative workup for myocardial ischemia, referral to a cognitive-behavioral therapist is reasonable.
(IIa, B-R)
573

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.
(I, B-NR)
573
  1. In patients with sickle cell disease who report acute chest pain, ACS should be excluded.
(I, C-LD)
573

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

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

  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.
(I, B-NR)
573
  1. For patients with stable chest pain and no known CAD categorized as low risk, CAC testing is reasonable as a first-line test for excluding calcified plaque and identifying patients with a low likelihood of obstructive CAD.
(IIa, B-R)
573
  1. 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.
(IIa, B-NR)
573

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

Anatomic Testing

  1. For intermediate-high risk patients with stable chest pain and no known CAD, CCTA is effective for diagnosis of CAD, for risk stratification, and for guiding treatment decisions.
(I, A)
573

Stress Testing

  1. 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 ischemia and for estimating risk of MACE.
(I, B-R)
573
  1. For intermediate-high risk patients with stable chest pain and no known CAD for whom rest/stress nuclear MPI is selected, PET is reasonable in preference to SPECT, if available to improve diagnostic accuracy and decrease the rate of nondiagnostic test results.
(IIa, B-R)
573
  1. For intermediate-high risk patients with stable chest pain and no known CAD with an interpretable ECG and ability to achieve maximal levels of exercise (≥5 METs), exercise electrocardiography is reasonable.
(IIa, B-R)
573
  1. In intermediate-high risk patients with stable chest pain selected for stress MPI using SPECT, the use of attenuation correction or prone imaging may be reasonable to decrease the rate of false-positive findings.
(IIb, B-NR)
573

Assessment of Left Ventricular Function

  1. In intermediate-high risk patients with stable chest pain who have pathological Q waves, symptoms or signs suggestive of heart failure, complex ventricular 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.
(I, B-NR)
573

Secondary Diagnostic Testing: What to Do If Index Test Results Are Positive or Inconclusive

Sequential or Add-on Diagnostic Testing
  1. For intermediate-high risk patients with stable chest pain and known coronary stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA, FFR-CT can be useful for diagnosis of vessel-specific ischemia and to guide decision-making regarding the use of coronary revascularization.
(IIa, B-NR)
573
  1. For intermediate-high risk patients with stable chest pain after an inconclusive or abnormal exercise ECG or stress imaging study, CCTA is reasonable.
(IIa, B-NR)
573
  1. For intermediate-high risk patients with stable chest pain and no known CAD undergoing stress testing, the addition of CAC testing can be useful.
(IIa, B-NR)
573
  1. For intermediate-high risk patients with stable chest pain after inconclusive CCTA, stress imaging is reasonable.
(IIa, B-NR)
573
  1. For intermediate-high risk patients with stable chest pain after a negative stress test but with high clinical suspicion of CAD, CCTA or ICA may be reasonable.
(IIb, C-EO)
573

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

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.
(I, A)
573
  1. For patients with known nonobstructive CAD and stable chest pain, it is recommended to optimize preventive therapies.
(I, C-EO)
573

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

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 guiding therapeutic decision-making.
(I, A)
573
  1. 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.
(I, A)
573
  1. 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 effective for guiding therapeutic decision-making.
(I, B-R)
573
  1. 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).
(IIa, B-NR)
573
Stress Testing
  1. 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.
(I, B-NR)
573
  1. 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.
(IIa, B-R)
573
  1. For patients with obstructive CAD who have stable chest pain despite GDMT, exercise treadmill testing 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.
(IIa, B-R)
573
  1. For patients with obstructive CAD who have stable chest pain symptoms undergoing stress PET MPI or stress CMR, the addition of MBFR is useful to improve diagnosis accuracy and enhance risk stratification.
(IIa, B-NR)
573

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

5.2.1.1. Patients With Prior Coronary Artery Bypass Surgery With Stable Chest Pain

  1. In patients who have had prior coronary artery bypass surgery presenting with stable chest pain whose noninvasive stress test results show moderate to severe ischemia, or in those suspected to have myocardial ischemia with indeterminate/nondiagnostic stress test, ICA is recommended for guiding therapeutic decision-making.
(I, C-LD)
573
  1. In patients who have had prior coronary artery bypass 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 stenosis or occlusion.
(IIa, C-LD)
573

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

Index Diagnostic Testing: Selecting the Appropriate Test

Anatomic Testing
  1. For symptomatic patients with known nonobstructive CAD who have stable chest pain, CCTA is reasonable for determining atherosclerotic plaque burden and progression to obstructive CAD, and guiding therapeutic decision-making.
(IIa, B-NR)
573
  1. 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.
(IIa, B-NR)
573
Stress Testing
  1. For patients with known extensive nonobstructive CAD with stable chest pain symptoms, stress imaging (PET/SPECT, CMR, or echocardiography) is reasonable for the diagnosis of myocardial ischemia.
(IIa, C-LD)
573

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

  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.
(IIa, B-NR)
573
  1. For patients with persistent stable chest pain and nonobstructive CAD, stress PET MPI with MBFR is reasonable to diagnose microvascular dysfunction and enhance risk stratification.
(IIa, B-NR)
573
  1. For patients with persistent stable chest pain and nonobstructive CAD, stress CMR with the addition of MBFR measurement is reasonable to improve diagnosis of coronary myocardial dysfunction and for estimating risk of MACE.
(IIa, B-NR)
573
  1. For patients with persistent stable chest pain and nonobstructive CAD, stress echocardiography with the addition of coronary flow velocity reserve measurement may be reasonable to improve diagnosis of coronary myocardial dysfunction and for estimating risk of MACE.
(IIb, C-EO)
573

Figure 14. Clinical Decision Pathway for INOCA

Recommendation Grading

Abbreviations

  • ACS: Acute Coronary Syndrome
  • AMI: Acute Myocardial Infarction
  • CABG: Coronary Artery Bypass Graft
  • CAC: Coronary Artery Calcium
  • CAD: Coronary Artery Disease
  • CCTA: Cardiac Computed Tomography Angiography
  • CDPs: Clinical Decision Pathways
  • CMR: Cardiac Magnetic Resonance
  • ECG: Electrocardiogram
  • ED: Emergency Department
  • EMS: Emergency Medical Services
  • FFR-CT: Fractional Flow Reserve With CT
  • GDMT: Guideline-directed Medical Therapy
  • ICA: Invasive Coronary Angiography
  • INOCA: Ischemia With Nonobstructive Coronary Artery
  • MACE: Major Adverse Cardiac Event
  • MBFR: Myocardial Blood Flow Reserve
  • METs: Metabolic Equivalents
  • MINOCA: Myocardial Infarction And Nonobstructive Coronary Arteries
  • MPI: Myocardial Perfusion Imaging
  • NSTE-ACS: Non-ST-elevation Acute Coronary Syndrome
  • PCI: Percutaneous Coronary Intervention
  • PE: Pulmonary Embolism
  • PET: Positron Emission Tomography
  • SIHD: Stable Ischemic Heart Disease
  • SPECT: Single-photon Emission Computerized Tomography
  • STEMI: ST-elevation Myocardial Infarction
  • TEE: Transesophageal Echocardiography
  • TTE: Transthoracic Echocardiography
  • VF: Ventricular Fibrillation
  • VHD: Valvular Heart Disease
  • VT: Ventricular Tachycardia
  • cTn: Cardiac Troponin
  • hs-cTn: High-sensitivity Cardiac Troponin

Source Citation

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: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Oct 28:CIR0000000000001029. doi: 10.1161/CIR.0000000000001029. Epub ahead of print. PMID: 34709879.

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