Chest pain diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Nuha Al-Howthi, MD[3]

Overview

Chest pain or chest pain equivalent may be referred as chest pain. Diagnosis of nontraumatic chest pain is frequent challenge for physicians. Initial evaluation is considered for life-threatening conditions such as ACS, aortic dissection, and pulmonary embolism , as well as nonvascular syndromes (eg, esophageal rupture, tension pneumothorax). So, therapy for those with less critical illnesses is reasonable. Although there are several life-threatening causes, chest pain usually reflects a more benign condition. The initial work-up is taking ECG, but exact history, physical examination, biomarkers, and other tests are necessary. There is no association between the intensity of symptoms and seriousness of disease and general similarity of symptoms among different causes of chest pain. A comprehensive history with all characteristics of chest pain including nature; 2) onset and duration, 3) location and radiation, 4) precipitating factors, 5) relieving factors, and 6) associated symptoms should be obtained to identify the underlying causes of chest pain.

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

Diagnostic Testing

Class I

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. (Level of Evidence: B-NR)

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. (Level of Evidence: C-LD)

3.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. (Level of Evidence: 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. (Level of Evidence: C-LD)

Electrocardiogram

Class I

1.In patients with chest pain in which an initial ECG is non-diagnostic, 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. (Level of Evidence C-EO)

2.Patients with chest pain in whom the initial ECG is consistent with an ACS should be treated according to STEMI and NSTE-ACS guidelines. (Level of Evidence C-EO)

Class IIa

1.In patients with chest pain and intermediate to-high clinical suspicion for ACS in whom the initial ECG is non-diagnostic, supplemental electrocardiographic leads V7 to V9 are reasonable to rule out posterior MI (Level of Evidence: B-NR)

Chest Radiography

Class I

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. (Level of Evidence C-EO)

Biomarkers

Class I

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 (Level of Evidence: 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.(Level of Evidence: B-NR)

3.Clinicians should be familiar with the analytical performance and the 99th percentile upper reference limit that defines myocardial injury for the cTn assay used at their institution. (Level of Evidence: C-EO)

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

Class I

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.(Level of Evidence: B-NR)

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

3.To standardize the detection and differentiation of myocardial injury in patients presenting with acute chest pain and suspected ACS, institutions should implement a CDP that includes a protocol for troponin sampling based on their particular assay. (Level of Evidence: C-LD)

4.In patients with acute chest pain and suspected ACS, previous testing when available should be considered and incorporated into CDPs (Level of Evidence: C-LD)

Class IIa

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. (Level of Evidence: B-NR)

Diagnostic Study of Choice

• Chest pain or chest pain equivalent may be referred as chest pain.
• The diagnosis of nontraumatic chest pain is a frequent challenge for clinicians in emergency department.
• Initial evaluation for work-up of chest pain is considered for life-threatening conditions such as ACS, aortic dissection, and pulmonary embolism , as well as nonvascular syndromes (eg, esophageal rupture, tension pneumothorax).
• Therapy for those with less critical illnesses is reasonable.
• Although there are several life-threatening causes, chest pain usually reflects a more benign condition.
• The initial ECG is important to the evaluation, but history, physical examination, biomarkers, and other tests are necessary.
• There is no direct association between the intensity of symptoms and seriousness of disease and general similarity of symptoms among different causes of chest pain.
• A comprehensive history that collects all the characteristics of chest pain including:

• Nature
• Onset and duration
• Location and radiation
• Precipitating factors
• Relieving factors
• Associated symptoms

Approach to patients with acute chest pain

• Patients with acute chest pain and suspected ACS should be categorized into low- versus intermediate- or high-risk groups once STEMI has been excluded.
• This risk stratification is important to guide subsequent management.
• Although most high-risk patients should undergo cardiac catheterization, these patients still require a clinical assessment to determine if invasive evaluation is appropriate.
• ECG, symptoms, risk factors of coronary artery disease (CAD), and cTn are used to estimate a patient’s probability of ACS or risk of 30-day major adverse cardiovascular events (MACE).
• The high sensivity cardiac troponin (hs-cTn) result may be more predictive than other clinical components of the risk score.
• If a single level of hs-cTn is below the limit of detection and chest pain symptoms initiated at least 3 hours before ED arrival, the patient is categorized to low risk group ( the probability of MACE within 30 days is ≤1%).
• If the patient is clinically still suspicious for ACS or diagnostic uncertainty remains after serial cTn measurement, repeating cTn assay later (beyond 3 hours for high-sensitivity and beyond 6 hours for conventional assays) is recommended.
• Intermediate risk group should be tested by cardiac imaging or undergoing cardiac catheterization.
• There is no need for additional tests for low risk patients.

Patient with acute chest pain

History, physical exam

ECG

Consider non cardiac cause

Consider nonischemic cardiac cause

Possible ACS

NO cardiac testing needed

Other cardiac testing as required

Obtain troponin

Risk stratification by clinical condition evaluation

Low risk

Intermediate risk

High risk

NO testing required, discharge

Further diagnostic test may be needed

Invasive coronary angiography

The above algorithm adopted from 2021 AHA/ACC/ASE Guideline

Recommendations for diagnostic tests of chest pain

ECG (class 1 )

❑ ECG is recommended in patients presenting with stable chest pain, unless in the evidence of noncardiac causes ❑ Patients with evidence of ACS or other life-threatening causes of chest pain should be transported urgently to hospital by EMS ❑ In patients presenting with acute chest pain, ECG should be taken within 10 min of arrival for evaluation of STEMI ❑ In patients presenting with acute chest pain in ED and suspected ACS, cTn should be measured as soon as possible after presentation

The above table adopted from 2021 AHA/ACC/ASE Guideline

Diagnostic algorythm based on the ECG

Chest pain

History, physical exam

ECG

STEMI

Diffuse ST elevation consistent with pericarditis

ST-depression,New T-wave inversion

Non diagnostic or normal ECG

New arrhythmia

Approach to STEMI

Management of pericarditis

Approach to NSTE-ACS

*Repeat ECG in the presence of persistent symptoms or change or elevated troponin level Considering Leads V7-V9 in suspicion of posterior MI

Approach to arrhythmia

The above algorithm adopted from 2021 AHA/ACC/ASE Guideline

• After initial evaluation, the next step is determining whether further diagnostic testing is required to establish the diagnosis.
• The initial assessment of patients presenting with acute chest pain is identification of patients with immediately life-threatening conditions such as ACS, acute aortic syndromes, and pulmonary embolism.
• Myopericarditis can be manifested as fulminant myocarditis with high mortality rate.
• Noncardiovascular syndromes whether identified life-threatening, including esophageal rupture, tension pneumothorax, and sickle cell chest crisis.
• Nonemergency causes of chest pain include costochondritis and other musculoskeletal, or gastrointestinal causes.

Algorithm for evaluation of suspected ACS with intermediate risk and NO history of coronary artery disease

Abbreviations: Recent negative test: Normal CCTA ≤ 2 years (no plaque, no stenosis) or negative stress test≤ 1 year ; High risk CAD: Left main stenosis ≥ 50%; significant three vessel disease (stenosis ≥ 70%) CAD: Coronary artery disease  ; CCTA: Coronary CT angiography; FFR-CT: Fractional flow reserve with CT; PET: Positron emission tomography; SPECT: Single-photon emission CT; INOCA: schemia and no obstructive coronary artery disease; CMR: Cardiovascular magnetic resonance imaging; CT:Computed tomography

Acute chest pain, intermediate risk, No known CAD

Perior testing

Yes

NO

Stress testing Exercise ECG Stress CMR Stress echocardiography Stress PET Stress SPECT

Coronary CT angiography

Recent negative test

Perior inconclusive or mildly abnormal stress test ≤ 1 year

Moderate severely abnormal test ≤ 1 year

Discharge

Coronary CT angiography (2a)

Invasive coronary angiography

Non obstructive CAD (stenosis<50%)= Discharge

Inconclusive stenosis

Obstructive CAD (stenosis)≥ 50%

High risk CAD or frequent angina=Coronary angiography

Non obstructive CAD (stenosis<50%)

Inconclusive result

Obstructive CAD (stenosis ≥ 50%)

FFR-CT, or stress testing

Medical therapy, discharge

Discharge

FFR-CT or stress test (2a)

*High risk CAD, frequent angina= Coronary angiography Making decision for medical therapy= Discharge

FFR-CT≤0.8, moderate to severe ischemia=Coronary angiography

FFR-CT>0.8, mild ischemia= medical therapy, discharge

FFR-CT ≤ 0.8 , moderate severely ischemia=Coronary angiography

FFR-CT>0.8, mild ischemia=Medical therapy, discharge

Negative or mildly abnormal=discharge

Moderately severe ischemia= Coronary angiography

Inconclusive=Coronary CT angiography

The above algorithm adopted from 2021 AHA/ACC/ASE Guideline

• Among patients with recent normal prior testing , no further testing is recommended.
• The intervals (1 year for stress testing, 2 years for CCTA without plaque or stenosis) are reasonable due to lack of atherosclerosis progression and low likelihood of cardiac events in patients with normal CCTA.
• When stress test is inconclusive or mildly abnormal in the past year, CCTA is recommended.
• It is recommended to test another study to rule-out of obstructive CAD when the previous result is inconclusive.
• For patients with presentation of acute chest pain and moderate-severe abnormalities on previous testing, without anatomic testing, invasive coronary angiography may be helpful for diagnosis of obstructive CAD.
• CCTA or stress test are the initial tests in patients without a previous diagnostic evaluation and no known CAD.
• When the initial stress test is inconclusive, second-line testing may be helpful.
• In patients with intermediate-risk who have intermediate stenosis on CCTA, FFR-CT, or stress testing may be indicated.
• Coronary angiography is recommended for high risk patients. However, patients with an intermediate-risk score may be recommended for CCTA or invasive coronary angiography in the context of moderate-severe ischemia or significant left ventricular dysfunction on diagnostic testing.
• Patients with coronary artery stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA may benefit from measurement of FFR-CT.
• CCTA is highly effective at ruling out the presence of plaque or stenosis and may be helpful to risk assessment and management in patients with no known CAD with inconclusive stress test results.
• Stress test with imaging may be indicated in patients with acute chest pain who have indeterminate stenosis on CCTA for evaluation of myocardial ischemia.

• Symptomatic patients with inconclusive or mildly abnormal stress tests often have an increased risk of MACE.
• Patients with previous stress testing often have atherosclerotic plaque and obstructive CAD lesion.

Recommendation for intermediate to high risk patients with stable chest pain and NO known CAD

Recommendation for intermediate to high risk patients with stable chest pain and NO known CAD

Anatomic test:

❑CCTA is reasonable for diagnosis, risk stratification, and guide therapy for intermediate to high risk patients and NO known CAD with stable chest pain (Class I, Level of Evidence A):

Stress test:

❑ For intermediate to high risk stable chest pain, use of stress imaging such as stress echocardiography, PET, SPECT /MPI,or CMR is effective to diagnosis of myocardial ischemia and determination the risk of MACE. (Class I, Level of Evidence B) ❑Exercise echocardiography is reasonable for stable chest pain and intermediate to high risk with interpretable ECG and ability to achieve more than 5 METS (Class IIa, Level of Evidence B) ❑ PET is preferred to SPECT to increase diagnostic accuracy and decrease the rate of nondiagnostic test result in intermediate- high risk stable chest pain (Class IIa, Level of Evidence B) ❑ Use of attenuation correction or prone imaging may increase the test accuracy in MPI SPECT (Class IIb, Level of Evidence B)

Assessment of left ventricular function:

❑ Transthoracic echocardiography is reasonable in intermediate-high risk stable chest pain and evidence of Q waves on ECG, heart failure signs and symptoms, complex ventricular arrhythmia, heart murmur (Class I, Level of Evidence B)

Add-on testing:

❑FFR-CCTA is recommended in intermediate-high risk patients with known CAD and stenosis 40%-90% in coronary CT angiography for determination of ischemia territory and decision making for revascularization (Class IIa, Level of Evidence B) ❑ CCTA is reasonable in intermediate-high risk stable chest pain when exercise ECG or stress imaging results are inconclusive or abnormal(Class IIa, Level of Evidence B) ❑ Stress imaging is recommended for intermediate to high risk stable chest pain when the result of CCTA is inconclusive (Class IIa, Level of Evidence B) ❑ For intermediate-high risk stable chest pain and negative stress imaging when clinical suspicion of CAD is high, CCTA or invasive coronary angiography may be reasonable (Class IIb, Level of Evidence B)

The above table adopted from 2021 AHA/ACC/ASE Guideline

• Among patients with recent normal prior testing , no further testing is recommended.
• The intervals (1 year for stress testing, 2 years for CCTA without plaque or stenosis) are reasonable due to lack of atherosclerosis progression and low likelihood of cardiac events in patients with normal CCTA.
• When a stress test is inconclusive or mildly abnormal in the past year, CCTA is recommended.
• It is recommended to test another study to rule-out of obstructive CAD when the previous result is inconclusive.
• For patients with the presentation of acute chest pain and moderate-severe abnormalities on the previous testing, without anatomic testing, invasive coronary angiography may be helpful for diagnosis of obstructive CAD.
• CCTA or stress test are the initial tests in patients without a previous diagnostic evaluation and no known CAD.
• When the initial stress test is inconclusive, second-line testing may be helpful.
• In patients with intermediate-risk who have intermediate stenosis on CCTA, FFR-CT, or stress testing may be indicated.
• Coronary angiography is recommended for high risk patients. However, patients with an intermediate-risk score may be recommended for CCTA or invasive coronary angiography in the context of moderate-severe ischemia or significant left ventricular dysfunction on diagnostic testing.
• Patients with coronary artery stenosis of 40% to 90% in a proximal or middle coronary segment on CCTA may benefit from measurement of FFR-CT.
• CCTA is highly effective at ruling out the presence of plaque or stenosis and may be helpful to risk assessment and management in patients with no known CAD with inconclusive stress test results.
• Stress test with imaging may be indicated in patients with acute chest pain who have indeterminate stenosis on CCTA for evaluation of myocardial ischemia.
• Symptomatic patients with inconclusive or mildly abnormal stress tests often have an increased risk of MACE.
• Patients with previous stress testing often have atherosclerotic plaque and obstructive CAD lesion.

Approach to stable chest pain and ischemia and no obstructive CAD (INOCA)

Stable chest pain suspected INOCA

Non-invasive test more prevalent Invasive test more comprehensive

Invasive coronary functional testing

Stress PET, Stress CMR, Stress echocardiography

CFR( coronary flow reserve)≥2 IMR (index of microcirculatory restriction) <25 Negative provocation study of Acetylcholine

Epicardial artery spasm > 90% with acetylcholine Reproduction of chest pain Ischemic changes in ECG

IMR (index of microcirculatory restriction)≥25 CFR (coronary flow reserve) <2 Coronary artery spasm and angina with ST depression during infusion or bolus of acetylcholine

NO ischemia and normal myocardial blood flow reserve

Ischemia and normal myocardial blood flow reserve

Ischemia , reduced myocardial blood flow reserve

Reduced myocardial blood flow reserve, No Ischemia

Noncardiac

Vasospasm

Coronary microvascular dysfunction

Low risk for cardiovascular event

INOCA, NO CMD (coronary microvascular dysfunction)

CMD (Coronary microvascular dysfunction), Ischemia

CMD

The above algorithm adopted from 2021 AHA/ACC/ASE Guideline