Coronary Syndrome (Acute, Suspected)

• Acute coronary syndromes (ACS) encompass a spectrum of conditions that are compatible with acute myocardial ischaemia and include patients presenting with recent clinical symptoms or signs, with or without changes on 12-lead electrocardiogram (ECG) and with or without acute elevations in cardiac troponin (cTn) concentrations 1, 2

• In 2021, there were an estimated 57,300 acute coronary events among people aged 25 and over – equivalent to 157 events every day 3

• In the emergency setting, acute chest pain represents around 5-10% of all presentations, yet only 15-25% of patients have a final diagnosis of ACS 4

• The two main manifestations of ACS are:

• Myocardial infarction (MI)

• Unstable angina (UA)

• The term myocardial injury is defined as evidence of elevated cardiac troponin values with at least 1 value above the 99th percentile upper reference limit

• Myocardial infarction (MI) is defined as myocardial injury with clinical evidence of acute ischaemia and with detection of abnormal troponin and at least one of the following:

• Symptoms of myocardial ischemia

• New ischemic ECG changes

• Development of pathological Q waves

Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology 5, 6.

• Unstable angina is defined as myocardial ischaemia at rest or on minimal exertion in the absence of acute cardiomyocyte injury/necrosis 6

• On the basis of ECG, patients with myocardial infarction (MI) can be divided into:

• ST-elevation myocardial infarction (STEMI)

• Non-ST elevation MI (NSTEMI) 

• Patients with ST-elevation myocardial infarction (STEMI) constitute 25-35% of patients with ACS 7

• Patients with STEMI tend to have elevated cardiac biomarkers and total vessel occlusion leading to transmural myocardial ischemia and infarction 8. The plaque pathophysiology is often different between STEMI and NSTEMI, but one key manifestation is that STEMI is often associated with total vessel occlusion, whereas NSTEMI often still have an open vessel.

• Patients with unstable angina usually have normal cardiac biomarker levels

• Invasive imaging (angiography) is usually performed promptly in patients with STEMI in order to provide reperfusion therapy by intervention or thrombolysis 

• In the Emergency Department setting, in patients with ACS, exclusion of acute MI, risk stratification and assessment for coronary artery disease is required

• The primary investigations in suspected ACS are ECGs and cardiac troponin measurement, serially repeated if required

• As current Hs-cTn assays quickly and accurately rule out AMI in the Emergency Department setting, imaging may not initially be required for diagnosis

• Resting TTE at the point of care in the emergency department has some limited benefit for detection of ischaemic myocardium by demonstration of abnormal wall motion and thereby risk stratification of suspected ACS patients 10, 13

• A 2025 report of the American College of Cardiology/American Heart Association Joint Committee 8 recommends TTE, which may include an initial point-of-care ultrasound by trained clinicians, for patients with cardiogenic shock, hemodynamic instability, or for suspected mechanical complications

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• Plain chest films (CXR) should be considered where a non-cardiac cause of chest pain is suspected 13, 14

• They can be useful in diagnosing some non-cardiac causes of chest pain

• A chest X-ray should be considered  to help exclude complications of ACS such as pulmonary oedema, or other diagnoses such as pneumothorax or pneumonia 15

• 12-19% of patients presenting with chest pain have abnormal findings on CXR  14, 16. However, findings are not always clinically significant. A retrospective study found that CXR potentially changed the management of only 3.8% of patients 17.

• Although CXR has a low yield in patients presenting with chest pain, it is easily accessible in the acute setting

• A chest radiograph should not delay urgent reperfusion therapy where indicated

• In patients with suspected ACS, once STEMI has been excluded, clinical decision pathways (CDPs) can categorise patients into low-, intermediate- and high-risk of major adverse cardiac events 10.

• There are several (non-imaging) CDPs (including HEART Pathway, ADAPT, and ESC 1, 6, 8, 10, 11Discussion of these algorithms is beyond the scope of this article.

• Algorithms for repeat high-sensitivity troponins at 1, 2 and 3 hours from presentation have been validated with negative predictive values over 99% to rule out AMI 12.

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• The presence of coronary artery stents and heavily calcified arteries may make the interpretation of CT angiography difficult due to artifact from the stents 18

• Studies have suggested that up to 11% of stents may be deemed non- evaluable 19

• The ESC guidelines 20 indicate that the use of MDCT coronary angiography in the acute setting in patients with stents has not been validated

• However, CTCA may still have an important role, especially in those who have limitations for stress testing, and may have good specificity if stent diameter is >3mm

• This has led to recommendations that patients with ACS and coronary artery stents in situ may be preferred over CTCA

• However, numerous advances in CT technology have resulted in the increased use of CTCA in the presence of stents where institutions have access to the advanced technology 18

• CT coronary angiography (CTCA) is an established technique that uses contrast to enhance the coronary arteries.

• CTCA has advantages as a gatekeeper over invasive cardiac angiogram for assessing coronary artery anatomy and has a higher sensitivity for plaque burden, and characterization (whereas invasive angio only assesses the lumen), but avoids the risks of an invasive procedure 15.

• It is recommended that the CAD-RADS system should be used for reporting CTCA 2.

• A normal CTCA has a high negative predictive value for coronary artery disease, between 97 and 99% 21, 22.

• Because of its high sensitivity, CTCA may allow reassurance and discharge of patients at low to intermediate risk who do not have significant coronary artery disease 7, 23.

• Multiple studies have validated the accuracy of CTCA to detect coronary artery stenosis and risk stratify patients at risk of a major adverse coronary event (MACE). Meta-analysis found CTCA to have a sensitivity of 96% and specificity of 79% for detecting 50% stenosis 13, 15.

• Limitations:

• With regard to patients with suspected ACS:

•  

• Functional imaging may be performed at rest using a variety of modalities (see below). Stress testing can be undertaken using exercise or a pharmacological agent.

• Note that there are contraindications to stress -testing:

• Ongoing pain. These patients require urgent cardiology referral for consideration of catheter angiography.

• Suspected or known aortic stenosis as a cause of the chest pain.

• Known cardiac dysfunction e.g. untreated heart failure from dilated cardiomyopathy or known restrictive heart disease with reduced ventricular filling, severe hypertrophic cardiomyopathy. Transthoracic echocardiogram (TTE) can be a good guide to this as a first line test prior to any stress testing.

• There is risk associated with inducing stress, with death in 1 in 10 000 and ventricular arrhythmia or MI in 1 in 5 000 15.

• In patients without ischaemic changes on 12-lead ECGs and normal hs-cTn, who are free from chest pain for several hours, stress imaging can be performed during hospitalization 6 or in an  outpatient setting.

• Functional imaging is performed when subjecting the heart to either exercise or pharmacological stress to assess the presence of stress-related ischaemia.

• Stress echo, MPS and cardiac MR have comparable accuracy so choice of functional test should be based on local and patient factors, taking into consideration availability and radiation exposure 26.

Modalities for functional imaging include:

• Transthoracic Echocardiography (TTE)

• SPECT Myocardial Perfusion Scintigraphy (MPS)/ SPECT Myocardial Perfusion Imaging (MPI)

• CT-Perfusion (CTP) and CT -Fractional Flow Reserve (CT-FFR)

• Stress perfusion Cardiac MRI

Transthoracic Echocardiogram (TTE)

• TTE can be performed as a resting procedure only or with the addition of an examination after stress induced by exercise or a pharmacological agent, such as dobutamine. Stress TTE is  equivalent to stress SPECT Myocardial Perfusion Imaging (MPI) in the acute setting in low to intermediate-risk patients 13.

• The 2023 European Society of Cardiology guidelines 1 recommend that TTE should be routinely available and performed or interpreted by trained healthcare professionals.

• In cases of suspected ACS with diagnostic uncertainty TTE can also be useful to suggest alternative aetiologies associated with chest pain (for example, acute aortic disease, RV signs in pulmonary embolism (PE)).

• Resting TTE at the point of care in the emergency department has some limited benefit for detection of ischaemic myocardium by demonstration of abnormal wall motion and thereby risk stratification of suspected ACS patients 13.

• A 2025 report of the American College of Cardiology/American Heart Association Joint Committee 8 recommends TTE, which may include an initial point-of-care ultrasound by trained clinicians, for patients with cardiogenic shock, hemodynamic instability, or for suspected mechanical complications.

• Stress echocardiogram (stress echo) is a functional test that can demonstrate cardiac ischaemia. Stress TTE induces focal wall-motion abnormalities in the region(s) of ischemia.

• In meta-analysis, the sensitivity of stress echo was 76-84% to detect 50% stenosis, with a specificity of 79-86% 15. The specificity is higher 88-90% for detecting stenosis over 70% 15.

• A normal stress echo has a good prognosis: normal results are associated with an annual risk of 0.4-0.9% for cardiac mortality or acute myocardial infarction 27.

• In patients with a normal ECG and non-elevated high-sensitivity cardiac Troponin levels who have been pain-free for some hours, stress TTE or stress SPECT imaging can be performed safely 28.

• NICE suggests stress echocardiography as one alternative for assessing myocardial ischaemia 15.

• Stress echo, MPS and cardiac MR have comparable accuracy so choice of functional test should be based on local and patient factors, taking into consideration availability and radiation exposure 26.

• If the study is suboptimal and unable to answer the clinical question, for example the acoustic window is restricted due to body habitus, cardiac MR could be considered.

Notes on TTE Method

• The testing method normally occurs as follows. A baseline resting reading is taken. The patient's heart is stressed through exercise (e.g. treadmill, supine bike) or pharmacologically for patients who are unable to exercise (e.g. dobutamine, dipyridamole or adenosine). A second reading is taken while the patient is at peak stress. The two readings are then interpreted together.

• Stress echocardiography (stress echo) is considered positive if there is abnormal ventricular wall motion or thickness in response to stress.

• Contrast echocardiography by using microbubbles to show myocardial capillaries can improve endocardial border definition  and assess segmental perfusion abnormalities which improves the diagnostic accuracy of stress echo  29, 30.

• Unlike MPS, there is no radiation dose from stress echo.

• Limitations:

• As with other forms of ultrasound imaging, the quality and hence overall diagnostic accuracy of echocardiography is limited by the experience of the sonographer and the interpreting physician.

• There is risk associated with inducing stress, with death in 1 in 10 000 and ventricular arrhythmia or MI in 1 in 5 000 15.

• Dipyridamole and adenosine are relatively contraindicated in severe asthma or profound obstructive pulmonary disease 15, 31.

SPECT Myocardial Perfusion Scintigraphy (MPS)/ SPECT Myocardial Perfusion Imaging (MPI):

• MPS uses single photon emission computed tomography (SPECT) which is a widely available and well validated method of functional cardiac imaging 32.

• Meta-analysis found MPS to have a sensitivity of 78% and specificity of 81% to detect 50% stenosis. MPS combined with CTCA has a sensitivity of 94% and specificity of 95% 15.

• In patients with active chest pain, an ECG with no ischemic changes, and an initial negative troponin, an urgent rest SPECT MPS is safe and clinically effective 13.

• In patients with a normal ECG and non-elevated high-sensitivity cardiac Troponin levels who have been pain-free for some hours, stress TTE or stress SPECT imaging can be performed safely 28.

• Rest-only MPI has been shown to be less sensitive than stress SPECT imaging if performed after the chest pain has subsided.

• A normal MPS has a good prognosis: a meta-analysis of 31 studies showed that the rate of death or myocardial infarction was 0.85% per year, which is comparable to event rates in populations without coronary artery disease 33.

• Stress echo, MPS and cardiac MR have comparable accuracy so choice of functional test should be based on local and patient factors, taking into consideration availability and radiation exposure 26.

Notes on MPS/MPI method

• A radioactive tracer (such as technetium-99m or thallium-201) is injected, followed by imaging of the myocardial uptake via SPECT. This is usually done twice; once with the patient at rest and later with the patient under stress, either during exercise or after administration of a vasodilator (such as dipyridamole or adenosine). The images at rest and under stress are assessed together. Areas of myocardium that show reversible defects (i.e. tracer uptake at rest, but not under stress) represent myocardial ischaemia. Areas that show irreversible defects (no tracer uptake at rest or under stress) represent infarcted myocardium.

• Limitations:

• High radiation dose: Generally, the radiation dose from MPS using technetium-99 is around 7mSv 34 but can be >20mSv with thallium-201 35. Dose also depends on the protocol used.

• MPS is time consuming, taking 3-4 hours 15. Some protocols comparing rest and stress images require the tracers to leave the heart which may take up to a week, requiring two visits and delaying results 36.

• A false negative result may occur when there is widespread ischaemia throughout the whole myocardium, such as in triple vessel disease 37. This is because the interpretation of the study relies on comparison of ischaemic areas to normal areas.

• There is a 1 in 10000 risk of death associated with stress induction 15.

CT - Fractional Flow Reserve (CT-FFR) 2, 13

• Invasive FFR is obtained at cardiac catheterisation and is the ratio comparing flow at hyperaemia proximal and distal to a stenosis. The technique derives the haemodynamic significance of a stenosis. However, it is an invasive test.

• CT-FFR is non-invasive and uses CTCA data and computational fluid dynamic modeling and/or machine learning to simulate FFR.

• The results of CT-FFR correlate reasonably well invasive FFR values obtained at catheterisation and produce clinical outcomes when incorporated into a management pathway. Using a CT-FFR-guided management pathway 13.

• Adding CT-FFR and stress-CT Perfusion (CTP) to CTA increases specificity, positive predictive value, and diagnostic accuracy over regular CTA 18 but is of limited availability.

• CT-FFR has been shown to accurately predict flow limiting lesions and can be utilised in place of other functional imaging tests 18.

• Some of the newer technologies like CT-FFR and CTP have now been shown to improve the accuracy of CAD diagnosis over and above CTA alone 18.

• CTP, CT-FFR and CMR are superior per patient sensitivity (88-90%), specificity (84-87%). The 2 most frequently performed functional imaging modalities of Stress Echocardiography and SPECT were the least accurate: 69% and 78% sensitivity, 77% and 79% specificity, respectively 18.

Cardiac Magnetic Resonance Imaging:

Cardiac Magnetic Resonance Imaging:

• In practice, cardiac MRI (CMRI) has a limited role in the assessment of ACS in the emergency department 7 in large part due to accessibility issues, lack of availability of out-of-hours trained staff and  the problems of scanning unstable patients

• However, potential roles are as follows:

• CMRI is particularly useful when echocardiography is of poor technical quality

• CMRI may be used to determine cardiac structure and function 1

• CMRI may help in the triage of patients with acute chest pain

• CMRI may be useful in MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) – comprising 5-10 % of ACS presentations

• In suspected acute myocardial ischaemia, cardiac MRI may show 7:

• Wall motion abnormalities

• Cine CMR has usefulness in demonstrating wall-motion abnormalities, which may accompany acute or chronic ischemic heart disease, and first-pass contrast-enhanced perfusion CMR can demonstrate myocardial perfusion abnormalities 13

• Reversible myocardial damage and oedema

• The use of T2-weighted CMR to identify myocardial oedema and can allow differentiation of acute from chronic infarction and is sensitive for acute myocardial damage 7

• CMRI can distinguish scarring and areas of viability and suggest the diagnoses of myocarditis and cardiomyopathy 1

• CMRI can assess myocardial perfusion and areas of myocardial injury 1

• Necrotic myocardium

• Alternative diagnoses

• CMRI may aid in risk stratification

• CMRI can also help predict outcomes in patients with non-ST elevation ACS 38

• CMR with delayed post-contrast imaging and oedema-weighted imaging provides assessment of the size, distribution, and transmural extent of acute or remote MI 13

• Late gadolinium enhancement of the subendocardium with variable transmural extent, following a coronary artery territory distribution indicates the number and location of coronary arteries involved 7

With regard to Stress CMRI:

• Indications for stress CMRI include patients with intermediate to high risk who have stable symptoms; it has high accuracy for prediction of significant coronary artery disease 7

• Studies have demonstrated high negative predictive value and excellent diagnostic performance of vasodilator-stress CMR in a low to intermediate-risk cohort when compared with nuclear MPI 39-41

•  CMRI can assess myocardial perfusion before and after pharmacological stress

• However, inotropic stress agents like dobutamine, are relatively contraindicated in patients with recent or active chest pain

• Stress CMRI is particularly useful in patients with known established coronary artery disease 1

• CMR has been shown to have similar or better performance to nuclear MPI in determining the degree of ischemic myocardium, which may be an important predictor of outcomes after revascularisation 13

• Stress echo, MPS and cardiac MR have comparable accuracy so choice of functional test should be based on local and patient factors, taking into consideration availability and radiation exposure 26

• CT - Fractional Flow Reserve (CT-FFR) 2, 13

  • Invasive FFR is obtained at cardiac catheterisation and is the ratio comparing flow at hyperaemia proximal and distal to a stenosis. The technique derives the haemodynamic significance of a stenosis. However, it is an invasive test.

  • CT-FFR is non-invasive and uses CTCA data and computational fluid dynamic modeling and/or machine learning to simulate FFR.

  • The results of CT-FFR correlate reasonably well invasive FFR values obtained at catheterisation and produce clinical outcomes when incorporated into a management pathway. Using a CT-FFR-guided management pathway 13.

  • Adding CT-FFR and stress-CT Perfusion (CTP) to CTA increases specificity, positive predictive value, and diagnostic accuracy over regular CTA 18.

  • CT-FFR has been shown to accurately predict flow limiting lesions and can be utilised in place of other functional imaging tests 18.

  • Some of the newer technologies like CT-FFR and CTP have now been shown to improve the accuracy of CAD diagnosis over and above CTA alone 18

  • CTP, CT-FFR, CMR superior per patient sensitivity (88-90%), specificity (84-87%). The 2 most frequently performed functional imaging modalities of Stress Echocardiography and SPECT were the least accurate: 69% and 78% sensitivity, 77% and 79% specificity, respectively 18.

• Patients who are at high risk and/or have ongoing pain should have urgent referral to cardiology for consideration of cardiac catheterisation