Approach

Patients with suspected acute coronary syndrome (ACS) require urgent evaluation. It is essential to establish whether the symptoms are a manifestation of an ACS and, if so, how likely it is for an adverse clinical event to occur.[2] Physicians need to first establish the patient's risk and follow current guidelines according to the initial risk assessment to choose an appropriate management strategy. The initial risk assessment includes the history, examination, ECG, and cardiac biomarkers.[2][5][79]

ECG

ECG is indicated as the first-line investigation in all patients. A 12-lead ECG should be performed and interpreted within 10 minutes of the point of first medical contact in any patient with suspected non-ST-elevation myocardial infarction (NSTEMI).[5][80]​ It is critical to immediate management to exclude ST-elevation myocardial infarction (STEMI). NSTEMI is indistinguishable from other types of ACS (STEMI or unstable angina) until ECG and biomarkers become available, because their pathophysiology and presentation are similar.[2] Typical ECG findings may be present, but many patients have a normal ECG at presentation and therefore serial ECGs, initially at 15- to 30-minute intervals, should be performed to detect the potential for development of ST-segment elevation or depression.[5]​ Where present, ECG findings in NSTEMI may be highly variable. Typically >1 mm of ST depression is present in 2 or more contiguous leads. Other potential findings include dramatic new T-wave inversions (Wellens waves) or transient ST elevation. ECG changes of ST elevation or new left bundle branch block should be evaluated as STEMI.[Figure caption and citation for the preceding image starts]: ECG showing ST depressionFrom the personal collection of Dr Syed W. Yusuf and Dr Iyad N. Daher, Department of Cardiology, University of Texas, Houston; used with permission [Citation ends].com.bmj.content.model.Caption@3bb75685[Figure caption and citation for the preceding image starts]: ECG showing ST depressionFrom the personal collection of Dr Syed W. Yusuf and Dr Iyad N. Daher, Department of Cardiology, University of Texas, Houston; used with permission [Citation ends].com.bmj.content.model.Caption@27f4a2cf

Continuous 12-lead ECG monitoring is a reasonable alternative to serial 12-lead recordings in patients whose initial ECG is nondiagnostic.[2] Supplemental ECG leads V7 through V9 may be useful in patients with nondiagnostic initial ECGs to rule out myocardial infarction (MI) due to left circumflex occlusion, and V3R and V4R may be useful to detect right ventricular MI.[5] Less commonly, the ECG may reveal a tachyarrhythmia or bradyarrhythmia precipitated by the MI.

History and examination

Patients presenting with chest pain or discomfort need immediate assessment for current or past history of coronary artery disease (CAD) and traditional risk factors (e.g., age, sex, diabetes, hypertension, cocaine use) to triage them as high priority.[7]​​ ACS is highly likely if there is a history of chest or left arm pain similar to previously documented angina pain, and a history of CAD (including MI). Angina pain is typically deep, poorly localized chest or arm pain described as a sensation of tightness, heaviness, aching, burning, pressure, or squeezing. The pain is most often retrosternal and can often radiate to the left arm, but may also radiate to the lower jaw, neck, both arms, back, and epigastrium, where it may mimic heartburn. Angina pain is associated with exertion or emotional stress (or less commonly with cold exposure) and relieved by rest.​[7]

Diaphoresis is a common associated symptom.[2]​ Shortness of breath is also common and is probably secondary to diminished cardiac output, but may also be due to underlying pulmonary congestion. Patients may express anxiety or appear anxious. They may also report a feeling of impending doom. Classically, events peak in the early morning hours, presumably due to hemodynamic stress caused by increased serum cortisol, adrenergic hormones, and platelet aggregation.[81]

Patients may present with a range of noncharacteristic symptoms, any of which may be the sole presenting symptom. These include weakness, nausea, vomiting, abdominal pain, and syncope. These are more common in women, older people, and those with diabetes.[5]​ Examination findings are usually nonspecific but may reveal hypertension or hypotension, the presence of third and fourth heart sounds, and paradoxical splitting of the second heart sound. Signs of heart failure (raised jugular venous pressure, bilateral crepitations on auscultation of the lungs) or cardiogenic shock may also be present, and these signify a worse prognosis.

Relief of chest pain with sublingual nitroglycerin is not necessarily diagnostic of myocardial ischemia and should not be used as a diagnostic criterion; other entities (e.g., esophageal spasm) may demonstrate a comparable response.[7] Pain described as sharp, fleeting (few seconds duration), or related to inspiration (pleuritic) or position, or which is shifting in location, suggests a lower likelihood of ischemia.[7]

Initial tests (non-ECG)

In addition to the ECG, the following tests must also be performed in all patients.

  • Cardiac troponins: a rise in the levels of cardiac troponins (>99th percentile of normal) are diagnostic for the condition and the use of high-sensitivity cardiac troponin assays have shortened the assessment time interval.[80]​ This test is readily available at most institutions. Cardiac troponins are more sensitive and specific markers of cardiomyocyte damage than creatine kinase (CK), its myocardial band isoenzyme (CK-MB), and myoglobin. In patients with MI, troponin levels rise rapidly (usually within 1 hour from symptom onset if using high-sensitivity assays) and remain elevated for several days. Therefore, with the advent of high-sensitive troponin assays (hs-cTn), other biomarkers (e.g., CK, CK-MB, and myoglobin) should not be used to diagnose NSTEMI.[4][5]​​​​[7]​​​[82][83]​​​​​ Similarly, for initial diagnostic purposes, routine measurement of additional biomarkers (e.g., heart-type fatty acid-binding protein [h-FABP] or copeptin) is not recommended in addition to hs-cTn.[5] For interpretation of hs-cTn, European Society of Cardiology recommends using the 0/1 hour or 0/2 hour “rule in” and “rule out” algorithms, which classify patients into one of three pathways according to the results of their hs-cTn values at 0 hours (time of initial blood test) and 1 hour or 2 hours later.​[5]

    • Rule-out pathway: for very low initial hs-cTn or no increase after 1/2 hours: these patients may be appropriate for early discharge and outpatient management.

    • Rule-in pathway: for high initial hs-cTN or an increase after 1-2 hours: most of these patients will require hospital admission and further evaluation.

    • Observe pathway: if neither of the above criteria is met: check hs-cTN at 3 hours and consider echocardiography.

  • Echocardiography: cardiac ultrasound may be useful for early triage of patients with suspected MI.[4] An urgent echocardiogram should always be performed in patients with cardiogenic shock or hemodynamic instability.[5][84]​ Point-of-care transthoracic echocardiogram can also be used to look for regional wall motion abnormalities of the left ventricle in patients with an atypical presentation or equivocal ECG, look for mechanical complications of acute MI (such as left ventricular function, right ventricular function, ventricular septal rupture, left ventricular free wall rupture, acute mitral regurgitation, pericardial effusion, cardiac tamponade) and for evidence to suggest alternative etiologies associated with chest pain (e.g., acute aortic disease, pulmonary embolism).[2][4]​​[5][84]​​[85]

    ​A predischarge echocardiogram is indicated for all patients post-acute MI to assess left ventricular function after coronary reperfusion therapy and to guide prognostication.[86][87]

  • Patients with a high index of suspicion who have negative serial ECGs and cardiac enzymes should be closely monitored in a telemetry or chest pain unit, as it may take time for cardiac markers to rise.[7]​​[88]​​​ 

  • Chest x-ray: indicated to exclude alternative causes for chest pain such as pneumothorax or a widened mediastinum in aortic dissection, or complications of ACS such as pulmonary edema due to heart failure.[80]

  • CBC: hemoglobin and hematocrit measurements may help to evaluate a secondary cause of NSTEMI (e.g., acute blood loss, anemia) and to evaluate thrombocytopenia to estimate risk of bleeding.

  • BUN and serum creatinine: creatinine clearance should be estimated in NSTEMI patients and the doses of renally cleared drugs should be adjusted appropriately. In chronic kidney disease patients undergoing angiography, iso-osmolar contrast agents may be preferred.​[89]

  • Serum electrolytes: electrolyte derangements may predispose to cardiac arrhythmias.

  • C-reactive protein (CRP): CRP is commonly ordered to rule out other causes of acute chest pain (e.g., pneumonia).

  • Liver function tests: useful if treatment with drugs that undergo hepatic metabolism is considered, and in the assessment of bleeding risk before starting anticoagulation. Impaired liver function tests may also suggest hepatic congestion in patients with concomitant heart failure.

  • Blood glucose levels: hyperglycemia is common in the setting of acute MI, with or without a history of diabetes.[90] There is controversy over whether tight glucose control may reduce risk of death and morbidity.[91]

Risk stratification

ACS management requires continuous risk stratification for death or recurrent MI. The American College of Cardiology/American Heart Association recommend that patients with suspected ACS are risk stratified based on the likelihood of ACS and adverse outcome(s) to further triage and assist in the selection of treatment options, particularly in settings where high-sensitivity cardiac troponin assays are not available.[2][7]​ Several risk scores exist that incorporate a number of variables such as clinical history, angina symptoms and equivalents, physical exam, ECG, renal function, and troponin levels. These variables can be used to estimate the risk of death and nonfatal cardiac ischemic events: for example, using the TIMI risk score or the Global Registry of Acute Coronary Events (GRACE) risk model.[2][92] [ Thrombolysis in Myocardial Infarction (TIMI) Score for Unstable Angina Non ST Elevation Myocardial Infarction Opens in new window ] [ GRACE Score for Acute Coronary Syndrome Prognosis Opens in new window ]

The TIMI risk score is composed of 7 risk indicators rated on presentation. One point is awarded for the presence of each of the following criteria:

  • Age >65 years

  • Presence of ≥3 CAD risk factors

  • Prior coronary stenosis >50%

  • ST-segment deviation on ECG

  • Elevated serum cardiac biomarkers

  • At least 2 anginal episodes in the past 24 hours

  • Use of aspirin in the past 7 days.

Patients with a TIMI score of 0 to 2 are low risk, 3 to 4 are intermediate risk, and 5 to 7 are high risk. All-cause mortality, rate of MI, and rate of urgent revascularization at 14 days increase in proportion to the number of risk factors present on the TIMI score.

The GRACE risk model is a web-based tool that can be used to predict in-hospital and post-discharge mortality or MI in patients following an initial ACS.

The Killip classification is another tool that can be used for risk stratification. This classification system risk stratifies patients with acute MI based on clinical evidence of left ventricular failure:

  • Class I: no evidence of CHF

  • Class II: presence of a third heart sound gallop, basilar rales, or elevated jugular venous pressure

  • Class III: presence of pulmonary edema

  • Class IV: cardiogenic shock.

The HEART Score incorporates elements of the patient’s history, ECG, age, risk factors, and troponin and is used for patients in the emergency room setting to assess risk of acute MI, percutaneous coronary intervention, coronary artery bypass graft (CABG), and death within 6 weeks of initial presentation.[93] [ HEART Score Opens in new window ]

Do not order a coronary artery calcium test in patients with known atherosclerotic disease, including those with stents and bypass grafts, as this offers limited incremental prognostic value for these individuals.[94][95]​​​[96]

Subsequent tests

Following initial workup and risk stratification, a range of additional investigations may be considered.

  • Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP): measurement of BNP or NT-pro-BNP may be considered to supplement assessment of global risk in patients with suspected ACS, in particular to predict risk of mortality, acute heart failure and development of atrial fibrillation (AF).​[5]

  • Lipid profile: this test is indicated in the first 24 hours of admission to the hospital to assess for lipid abnormalities and therefore the need for any lipid-lowering therapy.

  • Angiography: urgent and immediate angiography is indicated if the patients is clinically unstable or has any very high risk features: ongoing or recurrent pain despite treatment, hemodynamic instability (low blood pressure or shock) or cardiogenic shock, recurrent dynamic ECG changes suggestive of ischemia, a life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation) or cardiac arrest after presentation, or mechanical complications such as new onset mitral regurgitation.[2][5]​​[97]​ Patients with a history of anaphylaxis or allergy to contrast must be premedicated prior to angiography.[Figure caption and citation for the preceding image starts]: 64-slice CT angiography (A) and conventional angiography (B) showing a high-grade lesion in the mid-right coronary artery, indicated by the arrows. The arrowheads show artifacts that may be mistaken for lesionsFrom: Schussler JM and Grayburn PA. Heart. 2007 Mar;93(3):290-7 [Citation ends].com.bmj.content.model.Caption@57391e4c[Figure caption and citation for the preceding image starts]: 64-slice CT angiography of a patient with stable angina showing 3D reconstruction (A), curved reformatted images (B) and confirmation of a high-grade lesion on conventional angiography (C). The arrowheads show calcified plaques. Dx= diagnosisFrom: Schussler JM and Grayburn PA. Heart. 2007 Mar;93(3):290-7 [Citation ends].com.bmj.content.model.Caption@6ef7a6d4

  • Stress testing: stress testing, including treadmill exercise testing, may be useful and is recommended in low and intermediate pretest probability with a normal ECG and normal high sensitivity biomarkers to assist with guiding the need for an invasive strategy.[2][98][99]​​ The sensitivity and specificity of these tests increase when combined with either nuclear imaging to look for myocardial perfusion defects or echocardiography to assess wall motion abnormalities. The key positive finding on nuclear imaging stress tests is the presence of a reversible defect. This is an area of myocardium that becomes deprived of perfusion during increased myocardial demand and reperfuses on stopping the activity. This signifies stenosis within the coronary circulation that may be treated with percutaneous coronary intervention or CABG. Submaximal exercise testing can be performed at 4-7 days after myocardial infarction, while symptom limited testing can be performed at 14-21 days post-myocardial infarction, when the patient has been free of active ischemic or heart failure symptoms.[100] High risk patients should be considered for invasive strategy instead of stress testing.[101]​​

  • Coronary CT angiography (CCTA): this may provide noninvasive evaluation of coronary anatomy and atherosclerosis.[102]​ Renal failure is a relative contraindication. Patients with contrast allergy may be premedicated prior to angiography. Due to the high negative predictive value of CCTA, evidence suggests that CCTA is useful in patients with low to moderate risk of NSTEMI. When compared with the standard care of low-risk patients (observation, serial enzymes followed by stress testing) CCTA reduced time to diagnosis, reduced length of emergency department stay, and had similar safety.[103] CCTA is not indicated for patients with high-risk features (i.e., ischemic ECG changes, positive cardiac markers) so should not be used in high-risk emergency department patients presenting with acute chest pain.[5][84][95][104][Figure caption and citation for the preceding image starts]: 64-slice CT angiography of a patient with stable angina showing 3D reconstruction (A), curved reformatted images (B) and confirmation of a high-grade lesion on conventional angiography (C). The arrowheads show calcified plaques. Dx= diagnosisFrom: Schussler JM and Grayburn PA. Heart. 2007 Mar;93(3):290-7 [Citation ends].com.bmj.content.model.Caption@2aeed544[Figure caption and citation for the preceding image starts]: 64-slice CT angiography (A) and conventional angiography (B) showing a high-grade lesion in the mid-right coronary artery, indicated by the arrows. The arrowheads show artifacts that may be mistaken for lesionsFrom: Schussler JM and Grayburn PA. Heart. 2007 Mar;93(3):290-7 [Citation ends].com.bmj.content.model.Caption@5470857c

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