Approach to acute chest pain and acute coronary syndrome in adults

Authors: Isaac Kah Siang Ng, Yew Woon Chia, Kay Choong See, Desmond Boon Seng Teo

DEFINITIONs OF KEY TERMS

Acute chest pain (ACP) refers to pain/discomfort over the anterior thoracic region. The traditional Diamond classification characterises typical angina based on the presence of three cardinal features — substernal chest discomfort, precipitated by exertion and relieved by rest or glyceryl trinitrate (GTN).[1] Ischaemic chest pain is also described as crushing, heavy or tight in character,[23] and may radiate to the left arm, neck or jaw.[2] Currently, stratification of chest pain into typical and atypical angina is discouraged due to clinical ambiguity,[2] with the 2021 American Heart Association/American College of Cardiology guidelines proposing the use of ‘cardiac’, ‘possible cardiac’ and ‘noncardiac’ descriptors when assessing the likelihood of ischaemic chest pain based on symptom characteristics, patient’s age and cardiovascular risk factors.[2]

Acute coronary syndrome (ACS) is a subset of unstable/life-threatening forms of ischaemic heart disease (IHD) comprising unstable angina (UA), NSTEMI and ST segment elevation myocardial infarction (STEMI),[4] which typically warrant early coronary evaluation/intervention. In particular, UA is characterised by a crescendo pattern of angina, with increased frequency, duration (>15–20 min) and intensity, or pain at rest or refractory to GTN. Unstable angina is distinguished from NSTEMI by the absence of elevated cardiac biomarkers.

The fourth universal definition of myocardial infarction (MI) describes five aetiological categories of MI [Table S1, Supplemental Digital Appendix],[4] of which type 1 MI (T1MI; atherothrombotic disease) and type 2 MI (T2MI; myocardial oxygen supply/demand mismatch) are most commonly encountered. Diagnosis of MI requires a ≥20% rise and/or fall in troponin levels with at least one value >99th percentile of the upper reference limit, and at least one of the [2] (a) Clinical typical ischaemic symptoms; (b) Electrocardiographic new ischaemic ECG changes (e.g., new ST–T wave changes or new pathological Q waves); (c) Imaging imaging evidence of new regional wall motion abnormalities on echocardiography or new loss of viable myocardium on myocardial perfusion imaging (MPI); and (d) Anatomical identification of intracoronary thrombus on coronary angiography or during autopsy (for T1MI). Unlike MI, myocardial injury occurs when there is isolated hypertroponinaemia, without evidence of myocardial ischaemia.

PREVALENCE AND CAUSES

Acute chest pain accounts for 5%–11% of emergency department (ED) visits,[56] of which 5% have ACS[5] and 3% have a missed ACS diagnosis.[7] Chest pain can be broadly classified into cardiac and non-cardiac (e.g., respiratory, mediastinal, gastrointestinal, musculoskeletal/soft tissue) aetiologies [Table S2, Supplemental Digital Appendix], including life-threatening causes such as ACS, aortic dissection, pulmonary embolism, tension pneumothorax and perforated viscus.

CLINICAL APPROACH TO ACUTE CHEST PAIN

History taking

There are two components of history taking for ACP. Firstly, characterise the nature of chest pain using the SOCRATES [8] (a) Site: retrosternal/central (stable angina/ACS, pericarditis, gastro-oesophageal reflux disease [GERD]), right/left anterior chest (lung/pleural pathology, chest wall syndromes), epigastrium (gallstone disease, pancreatitis, peptic ulcer disease [PUD]), costochondral junction (costochondritis); (b) Onset: sudden (ACS, aortic dissection, perforated viscus), gradual (other subacute pathologies); (c) Character: heavy/ crushing/tightness (anginal), pleuritic (pleurisy), sharp/stabbing (pericarditis, pleurisy, neuropathic, chest wall syndromes), burning (GERD, PUD); (d) Radiation: to neck/jaw/arm (ACS), back (aortic dissection, pancreatitis), right shoulder (gallstone disease); (e) Alleviating rest/GTN use (anginal), sitting up and leaning forwards (pericarditis, pancreatitis), antacids)(GERD), analgesia/anti-inflammatory medications (musculoskeletal); (f) Timing: association with meals (GERD, PUD, gallstone disease); (g) Exacerbating exertion/emotional stress (anginal), lying flat (GERD, pericarditis, pancreatitis), deep inspiration (pleurisy), palpation/chest wall movement /coughing (musculoskeletal); and (h) Severity: pain score 1–10.

Secondly, identify associated symptoms, significant negatives and predisposing risk factors to assess the likelihood of clinical differentials. For example, patients with MI may have anginal chest pain associated with breathlessness, palpitations and diaphoresis, with a background of significant cardiovascular risk factors. However, we must also be cognisant of atypical presentations of MI, which are more commonly observed in elderly, female and diabetic patients.[9]

Physical examination

Clinical examination comprises four main objectives. Firstly, haemodynamic assessment is required to identify patients who need urgent resuscitation, stabilisation and escalation of care. For example, the presence of hypotension in MI may be concerning for cardiogenic shock, whereas inter-arm differential systolic blood pressures >20 mmHg may be suggestive of aortic dissection. Secondly, a detailed cardiovascular examination is required to identify complications of myocardial ischaemia, such as acute decompensated heart failure, ventricular septal rupture, ischaemic mitral regurgitation and tachy/bradyarrhythmias. Thirdly, a targeted examination to exclude other differentials should be performed, such as respiratory examination for features of pneumonia/pneumothorax, abdominal examination for peritonism in perforated viscus and chest wall inspection/palpation for musculoskeletal pathologies. Finally, observe for features suggestive of atherosclerotic disease (e.g., Frank’s earlobe crease sign[10]), underlying cardiovascular risk factors (insulin injection marks, xanthelasma/tendon xanthoma, nicotine/tar stains) and microvascular/macrovascular end-organ complications (e.g., previous coronary artery bypass graft and vein harvesting scars, residual hemiplegia from previous stroke, stigmata of end-stage renal disease or presence of dialysis vascular access, signs of peripheral arterial disease, peripheral neuropathy).

INVESTIGATIONS FOR ACUTE CHEST PAIN

Broadly, investigations for ACP include ECG, biomarkers (cardiac enzymes and other laboratory tests) and imaging modalities.

Firstly, ECG is a standard point-of-care test in all patients with ACP. In patients with persistent symptoms or high clinical suspicion of ACS, serial ECG should be repeated to look for evolving ST–T wave changes of myocardial ischaemia. There are classical ECG features of STEMI [Figure S3A, Supplemental Digital Appendix] and STEMI equivalents, including left main coronary artery occlusion [Figure S3B, Supplemental Digital Appendix], Wellen’s syndrome (suggestive of critical proximal left anterior descending [LAD] coronary artery stenosis) [Figure S3C, Supplemental Digital Appendix] and de Winter T waves (suggestive of acute proximal LAD occlusion) [Figure S3D, Supplemental Digital Appendix]. A new-onset left bundle brunch block (LBBB) used to be considered a STEMI or occlusion MI equivalent; however, this finding should be interpreted in the context of clinical and biochemical findings to determine if there is concern of ongoing myocardial ischaemia that warrants urgent reperfusion therapy.[11] In cases of pre-existing LBBB, modified Sgarbossa’s criteria are used to identify STEMI.[12] New-onset right bundle brunch block in occlusion MI may also suggest an occlusion of a proximal septal perforating branch of LAD,[13] which is associated with a large infarct size, higher rates of heart failure, heart block and overall mortality.[14] On the other hand, ECG features of NSTEMI typically include ST depressions and/or T wave inversions [Figure S3E, Supplemental Digital Appendix]. Recently, the Aslanger pattern was described in 6.3% of NSTEMI patients, which portends an inferior occlusive MI, associated with larger infarct size, multivessel disease and higher mortality rates.[15]

Secondly, high-sensitivity cardiac troponins are gold standard biomarkers for diagnosing MI.[4] High-sensitivity troponin I has a higher diagnostic accuracy than troponin T, with sensitivity and specificity >90% when performed on admission.[16] In patients presenting <6 h from the onset of chest pain with a normal first set of high-sensitivity troponins, trending of a second set of troponins at the 3-h mark confers at least 98% negative predictive value for MI.[17] Nonetheless, serial troponin testing beyond the initial two sets may occasionally be helpful to assess for re-infarction in the presence of new/recurrent ischaemic chest pain and/or ECG changes[4] or for prognostication in acute myocarditis.[18]

Thirdly, imaging modalities often include chest radiographs (CXR), point-of-care ultrasound (POCUS) and formal transthoracic echocardiogram. The CXR is useful to assess for cardiopulmonary pathologies such as pulmonary oedema from acute decompensated heart failure, pneumonia or pneumothorax. The POCUS may identify territorial regional wall motion abnormalities suggestive of myocardial ischaemia or reduction in left ventricular ejection fraction,[19] left ventricular apical hypokinesia with basal sparing that may suggest Takotsubo cardiomyopathy in the appropriate context,[20] and look for cardiopulmonary features of aortic dissection,[19] pulmonary embolism, pneumothorax, pneumonia, pericardial and pleural effusion.[21] Advanced imaging modalities include anatomical and functional imaging studies for stable patients with intermediate pretest probability of coronary artery disease (CAD), as well as cardiac magnetic resonance imaging for diagnosis of myocarditis based on Lake Louise criteria.[22]

Finally, coronary angiography should be offered to all patients with ACS, in the absence of contraindications, but the timing of coronary evaluation and revascularisation depends on the type and risk stratification of MI. The overall approach to differentiating the causes of ACP is summarised in Table S3 [see Supplemental Digital Appendix], with a summarised algorithm presented in Figure 1.

DIAGNOSTIC EVALUATION OF CORONARY ARTERY DISEASE

Diagnostic workup for CAD may be performed through invasive or non-invasive coronary evaluation, anatomical or functional imaging, and stress or non-stress testing modalities, depending on the pretest probability of CAD.[2] This is because in low pretest probability cases, an abnormal test is more likely to be a false positive, whereas in high pretest probability situations, a normal test is more likely to be a false negative.[23] Hence, patients with low pretest probability of CAD should avoid cardiac testing, while patients with intermediate pretest probability of CAD may undergo cardiac stress testing (e.g., exercise ECG, stress myocardial perfusion imaging, stress echocardiogram, stress cardiac magnetic resonance imaging) or non-stress cardiac imaging (e.g., computed tomography coronary angiogram), and patients with high pretest likelihood of CAD should directly undergo diagnostic coronary angiogram to detect and quantify the severity of coronary athero-occlusive disease.

Several predictive models exist for risk stratification of patients with suspected CAD, including the updated Diamond–Forrester (UDF) classification,[24] CAD consortium 2[25] and CONFIRM registry scores.[26] In a multicentre study of the utility of the above risk scores in predicting obstructive CAD in patients with suspected CAD detected on computed tomography coronary angiogram, the CAD consortium 2 score had the best discrimination with area under the receiver-operating curve and ability to reclassify low-risk patients at 10% probability threshold.[27] Locally, a novel PRECISE risk score has recently been developed and validated for use in Southeast Asian patient cohorts.[28]

Importantly, cardiac stress testing should be avoided in haemodynamically unstable patients, within 48 h post-MI, in high-risk UA and in the presence of significant cardiac arrhythmias.[229] Moreover, decision to work up suspected CAD should take into consideration the patient’s goals of care, benefits and risks of testing, and how the diagnostic findings will change the overall management.

RISK STRATIFICATION OF ACUTE CHEST PAIN

The History, ECG, Age, Risk factors and Troponin (HEART) score[30] is a practical tool in ED settings for risk stratification of patients presenting with ACP into low-risk (0–3), moderate-risk (4–6) and high-risk (7–9) categories to guide disposition and subsequent management of ACP and ACS.

In cases of proven ACS (UA, NSTEMI, STEMI), the Thrombolysis in MI[3132] and Global Registry of Acute Coronary Events (GRACE)[33] scores scores are useful for predicting clinical outcomes. In particular, a high GRACE score >140 portends poorer prognosis and is considered a high-risk feature in NSTEMI that warrants early intervention within 24 h.[17]

APPROACH TO HYPERTROPONINAEMIA

There are many causes of hypertroponinaemia [Table S4, Supplemental Digital Appendix], as serum troponins can be elevated in any condition that leads to myocardial injury/necrosis, from acute (e.g., sepsis, acute kidney injury, myocarditis) and chronic (e.g., chronic heart failure with elevated left ventricular end-diastolic pressure, chronic kidney disease) myocardial injury to full-blown MI (e.g., T1MI or T2MI).

For simplicity, a ‘three-step approach’ to hypertroponinaemia can be adopted [Figure 2]:

Exclude chronic myocardial injury (in the appropriate clinical context, e.g., chronic structural heart disease, chronic kidney disease) by the absence of an acute >20% rise and/or fall in troponin levels on serial measurements.Differentiate between acute myocardial injury and acute MI by looking for symptoms/ECG/radiological/angiographic changes suggestive of myocardial ischaemia.In patients with acute MI, differentiate between T1MI and T2MI by looking for clinical precipitants of myocardial oxygen supply/demand mismatch (e.g., severe anaemia, sepsis, acute kidney injury).

In practice, differentiating between T1MI and T2MI is often challenging. In general, T2MI patients are commonly older,[34] female[3435] and have multiple comorbidities (e.g., renal insufficiency),[343536] whereas T1MI patients are more likely to have prior MI[35] or revascularisation.[3435] However, both the absolute cardiac troponin levels and percentage change over time are not useful to discriminate between T1MI and T2MI.[37] Coronary angiography is useful to detect coronary atherothrombotic disease with plaque rupture if T1MI is suspected.[36]

In MI cases with clear precipitants of myocardial oxygen supply/demand mismatch and a low pretest probability of T1MI, it is reasonable to treat the underlying clinical event first without pursuing urgent coronary evaluation. Nonetheless, in patients with significant cardiovascular risk factors or known CAD, a low threshold for coronary evaluation is often required, especially if patients develop high-risk features such as recurrent/persistent chest pain, haemodynamic or electrical instability or dynamic ECG changes suggestive of myocardial ischaemia.

In hospitalised patients, common events precipitating myocardial ischaemic imbalance include anaemia, sepsis, renal impairment, cardiac arrhythmias and postoperative state.[36] For example, in severe anaemia, there is reduced oxygen-carrying capacity and myocardial oxygen delivery, while the concomitant hyperdynamic circulation increases myocardial oxygen demand. In sepsis, MI may be inflicted through infective, cytokine and catecholamine-mediated mechanisms.[38] In renal impairment, hypertroponinaemia may be related to clinically silent micro-infarctions or associated left ventricular hypertrophy.[39]

Finally, in unexplained cases of elevated troponins without evidence suggestive of myocardial injury/ischaemia, there is an entity of spurious hypertroponinaemia caused by laboratory assay interference, for instance, due to the presence of heterophile antibodies that may be acquired from iatrogenic (e.g., blood products, monoclonal antibody therapies, vaccinations) and non-iatrogenic (e.g., rheumatoid factor in rheumatoid arthritis and other autoimmune conditions) sources.[40] The possibility of heterophile antibody interference with laboratory troponin assay may be investigated through repeat testing on different analyser platforms or by adding heterophile-blocking reagents.[40]

MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION

In general, management of MI depends on the aetiological subtype (T1MI vs. T2MI) and extent/severity of MI (STEMI vs. NSTEMI).

The management of T1MI (atherothrombotic MI) comprises the following five key components, with differences in the choice of antithrombotic agents and timing of revascularisation depending on the extent of ischaemia (STEMI vs. NSTEMI):

Acute resuscitation and airway, breathing, circulation for the haemodynamically unstable patient, advanced cardiac life support in cardiac arrests, ‘cath lab activation’ for confirmed STEMI and high-risk NSTEMI cases;Revascularisation target immediate percutaneous coronary intervention (PCI) (‘door-to-balloon time’) within 90 min for STEMI; target PCI within 72 h for NSTEMI in the absence of high-risk features that may warrant earlier or immediate intervention (e.g., recurrent or persistent chest pain, haemodynamic or electrical instability or presence of dynamic ECG ST–T wave changes suggestive of myocardial ischaemia);[41] in 2018, the TRANSIENT trial studied the entity of ‘transient STEMI’ (i.e., attaining ST segment normalisation and symptomatic relief before definitive revascularisation) and found that these patients generally had small infarct sizes and had no significant differences in major adverse cardiac events between adopting an immediate (as for STEMI) versus delayed (as for NSTEMI) reperfusion strategy;[42]Symptomatic sublingual GTN (500 mcg pro re nata, can be repeated 5 min apart) or intravenous GTN (initiate at 15–20 mcg/min, then uptitrate by 10–15 mcg/min at 15–30 min intervals to the desired effect) for symptomatic relief of anginal chest pain;Guideline-directed medical (a) dual antiplatelet therapy (DAPT) with aspirin (300 mg loading dose, followed by 100 mg OM maintenance dose) and either clopidogrel (300/600 mg loading dose, followed by 75 mg OM maintenance dose), ticagrelor (180 mg loading dose, followed by 90 mg BD maintenance dose) or prasugrel (60 mg loading dose, followed by 10 mg OM maintenance dose); (b) consider subcutaneous low-molecular-weight heparin for NSTEMI planned for early PCI (e.g., subcutaneous enoxaparin 1 mg/kg BD, with dose reduction to 1 mg/kg OD if estimated glomerular filtration rate [eGFR] 15–29 mL/min and contraindicated if eGFR <15 mL/min), or intracoronary heparin during PCI; (c) beta-blockers (e.g., carvedilol, metoprolol and bisoprolol); (d) angiotensin converting enzyme inhibitors (ACE-I; e.g., captopril, enalapril and lisinopril); and (e) statins (e.g., atorvastatin);Post-MI cardiac rehabilitation, preventive health (vaccinations), lifestyle modifications, optimisation of cardiovascular risk factors and longitudinal follow-up.

For T2MI, guideline-directed medical treatment remains fairly scarce. In the presence of clear clinical precipitants of myocardial ischaemic imbalance, management largely involves treating the underlying cause, with the potential role of beta-blockers to reduce myocardial oxygen demand, provided there are no contraindications such as hypotension, bradycardia or acute heart failure.[36] Depending on the patient’s pretest probability of IHD and goals of care, non-urgent cardiac evaluation for underlying CAD may be considered.[36]

TAKE HOME MESSAGES

Acute chest pain can be caused by cardiac and non-cardiac (respiratory, mediastinal, gastrointestinal, musculoskeletal and others, e.g., psychogenic) pathologies.Approach to chest pain involves clinical characterisation of the chest pain with its associated features and risk factor assessment, with appropriate use of investigations including ECG, cardiac biomarkers and radiological investigations.Myocardial injury refers to isolated hypertroponinaemia, whereas MI requires clinical, electrocardiographic, imaging or angiographic evidence of acute myocardial ischaemia.T1MI is caused by acute atherothrombosis in the presence of underlying atherosclerotic coronary disease, whereas T2MI is precipitated by clinical insults that lead to significant myocardial oxygen supply/demand mismatch.Treatment of MI comprises five key components of acute resuscitation/stabilisation, revascularisation therapy, symptomatic treatment, guideline-directed medical therapy, and post-ACS rehabilitation, follow-up and optimisation of cardiovascular risk factors.

Financial support and sponsorship

Nil.

Conflicts of interest

See KC is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article.

Supplemental digital content

Appendix at http://links.lww.com/SGMJ/A84