Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department

INTRODUCTION — 

An emergency department patient with a suspected acute coronary syndrome (ACS) should be evaluated and treated rapidly. Initial management steps should be prompt but methodical and evidence-based, and undertaken before or during the time the diagnosis is being established.

ACS applies to patients with evidence of myocardial ischemia or infarction. ACS can be further classified into ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTEACS). The latter was traditionally comprised of non-ST-elevation myocardial infarction (NSTEMI) and unstable angina, but the diagnosis of unstable angina is uncommon in the era of high-sensitivity troponin. (See "Acute coronary syndrome: Terminology and classification".)

The diagnosis of ACS/myocardial infarction (MI) depends upon the characteristics of the chest pain (if present), specific associated symptoms, abnormalities on electrocardiogram (ECG), and levels of serum markers of cardiac injury (ie, troponin). Myocardial infarction is characterized by a typical rise or fall in serum troponin. (See "Diagnosis of acute myocardial infarction".)

TOPIC SCOPE — 

This topic and the associated table (table 1) review the initial management of an emergency department (ED) patient with clinical features (see 'Clinical features of acute coronary syndrome' below) or electrocardiogram (ECG) manifestations (see 'Electrocardiogram assessment' below) suspicious for ACS.

The subsequent management (ie, "rule out myocardial infarction") of patients judged to be at low or intermediate risk for ACS after the initial ED evaluation described below is discussed separately. (See "Evaluation for suspected non-ST-segment elevation acute coronary syndromes".)

Immediate therapy should begin following a provisional diagnosis of ST-elevation myocardial infarction (STEMI) or of non-ST-elevation ACS (NSTEACS) (ie, "ruled in"). The approach to management of STEMI and other aspects of NSTEACS management are presented separately. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

Many life-threatening conditions can cause chest pain (table 2) and dyspnea (table 3), and premature diagnostic closure must be avoided. The general approaches to an ED patient with these symptoms, especially when conditions other than ACS are high on the differential diagnosis, are presented separately. (See "Approach to the adult with nontraumatic chest pain in the emergency department" and "Approach to the adult with dyspnea in the emergency department".)

GUIDANCE FOR INSTITUTIONS

Multidisciplinary teams and protocols — The American College of Cardiology (ACC) and the American Heart Association (AHA) recommend that all hospitals establish multidisciplinary teams to develop guideline-based, institution-specific written protocols for triaging and managing patients who present with symptoms suggestive of myocardial ischemia [1]. Immediate cardiology consultation should be available for cases in which the initial diagnosis and treatment plan are unclear or are not addressed directly by available protocols.

For patients with ST-elevation myocardial infarctions (STEMI), rapid implementation of primary percutaneous coronary intervention (PCI) is more likely to be achieved if the hospital protocol involves immediate activation of the PCI team by prehospital emergency medical services (EMS) [2] or emergency department clinician followed by immediate transfer of the patient to the catheterization laboratory [3].

Standing orders for initial rapid ECG — In general, a 12-lead resting electrocardiogram (ECG) should be obtained within 10 minutes of emergency department (ED) arrival in all patients with possible coronary-related ischemia, ideally by standing order. This includes all patients with chest discomfort that do not have an obvious noncardiac cause. The institution's specific chest pain protocol should be initiated if the history or symptoms are suggestive of acute ischemia. (See 'History' below.)

The ECG provides an important basis for initial diagnosis and management and should immediately be shown to an emergency clinician for interpretation. (See 'Electrocardiogram assessment' below.)

An ECG is also obtained routinely in older adults or patients with diabetes with symptoms of unclear etiology, such as dyspnea, nausea, or malaise; patients with syncope; and patients with symptoms or signs consistent with an arrhythmia. A substantial number of patients ultimately diagnosed with an ACS, particularly older patients, females, and patients with diabetes, present with symptoms such as dyspnea or weakness without chest discomfort or do not manifest clear signs of ischemia in their initial ECG [4]. Large observational studies report that ECG acquisition is frequently delayed and that females are significantly less likely to be assessed within the recommended 10 minutes or to receive testing with a cardiac biomarker [5-7]. (See 'Atypical presentations' below.)

However, it can occasionally be difficult to identify at triage or early in the ED evaluation which younger adult patients should be evaluated with an ECG. A research group has proposed a rule for prioritizing immediate ECG in ED patients at risk for STEMI [8]. This should not replace clinical judgment but provides evidence for clinicians creating appropriate ED triage protocols or determining which patients need an ECG, including those presenting without chest pain. The rule recommends that a patient with any of the following should have an immediate ECG:

●Over 30 years with chest pain

●Over 50 years with any of the following: dyspnea, altered mental status, upper extremity pain, syncope, or weakness

●Over 80 years with abdominal pain, nausea, or vomiting

This rule was derived and validated using information from over three million ED visits (including 6464 STEMI cases) that were part of a state-wide health surveillance database. When applied to the validation sample (3294 STEMI cases), the rule had a sensitivity of 91.9 percent (95% CI 90.9-92.8) and a specificity of 76.2 percent (95% CI 76.1-76.2).

Prospective validation of this decision rule in other patient populations is needed before widespread adoption can be recommended. Among the rule's limitations are its relatively low sensitivity and age cutoffs, which may be too high in some settings. It is worth reiterating the importance of paying close attention to females, older patients, patients with diabetes with symptoms consistent with ACS, and using a low threshold for obtaining an ECG in such patients.

CLINICAL FEATURES OF ACUTE CORONARY SYNDROME

History — ACS is a possibility in any adult who presents to the emergency department (ED) complaining of chest discomfort or dyspnea. Certain characteristics of the patient's chest discomfort and associated symptoms increase the likelihood of ACS, while others make the diagnosis unlikely. A personal or family history of ACS or other cardiovascular disease, older age, diabetes, dyslipidemia, cigarette smoking, hypertension, or cocaine use all increase the likelihood. (See "Overview of established risk factors for cardiovascular disease".)

Many patients with ACS present with symptoms such as dyspnea or malaise, either alone or in addition to chest pain. Females are more likely to have associated dyspnea than males. Patients who are older or who have diabetes are more likely to present with symptoms such as dyspnea, weakness, nausea and vomiting, palpitations, and syncope, and may not manifest chest discomfort. (See 'Atypical presentations' below.)

Ischemic chest pain — Pain from coronary-related ischemia is more often characterized as nonfocal chest discomfort or pressure rather than pain, is generally gradual in onset, and is exacerbated by activity. Symptoms associated with the highest relative risk of myocardial infarction include radiation to an upper extremity, particularly when there is radiation to both arms, and pain associated with diaphoresis, nausea, or vomiting [9-11]. An important question is whether current pain is reminiscent of prior myocardial infarction.

The OPQRST mnemonic plus associated symptoms is a helpful aid to distinguish features of ischemic from noncardiac pain. Of note, no single pain characteristic has sufficient positive or negative predictive value to definitively diagnose or exclude ACS.

●Onset – Ischemic pain is typically gradual in onset, although the intensity of the discomfort may wax and wane. Angina occurs more commonly in the morning due to a diurnal increase in sympathetic tone, increasing heart rate, blood pressure, vessel tone and resistance, and promoting platelet aggregation [12,13].

●Provocation and palliation – Ischemic pain is generally provoked by an activity or situation that increases myocardial oxygen demand, including exercise, cold, emotional stress, and sexual intercourse [10,14]. Ischemic pain generally does not change with respiration, position, or palpation of the chest wall, but the presence of any of these does not exclude ACS. Ischemic pain may or may not respond to nitroglycerin and, if there is improvement, this may only be temporary. Relief of pain following the administration of therapeutic interventions (eg, nitroglycerin, "gastrointestinal cocktail" of viscous lidocaine and antacid) does not reliably distinguish nonischemic from ischemic chest pain [15-19]. Postprandial pain may be anginal, especially in patients with severe ischemia (eg, left main or three-vessel coronary disease) [20].

Relief of chest discomfort with nitroglycerin is not specific for ACS, since it can also improve pain from esophageal spasm or other gastrointestinal problems. Pain that responds to sublingual nitroglycerin is frequently thought to have a cardiac etiology. However, in a study of 459 patients who presented to an ED with chest pain and were admitted to the hospital, the percentage of patients who had relief of chest pain with nitroglycerin was similar among the 141 patients with ACS and the 275 patients without active coronary disease (35 versus 41 percent experienced relief) [15].

●Quality – Ischemic pain is often characterized more as a discomfort than pain, and it may be difficult for the patient to describe. Terms frequently used by patients include squeezing, tightness, pressure, constriction, crushing, strangling, burning/heartburn, fullness in the chest, band-like sensation, knot in the center of the chest, lump in throat, ache, heavy weight on chest (elephant sitting on chest), like a bra too tight, and toothache (when there is radiation to the lower jaw). It is generally not described as sharp, fleeting, knife-like, stabbing, or like "pins and needles" [10].

Increased pain severity does not appear to correlate with an increased likelihood of acute myocardial infarction [21].

In some cases, the patient cannot qualify the nature of the discomfort but places a clenched fist in the center of the chest, known as the "Levine sign."

●Radiation – Ischemic pain often radiates to other parts of the body including the upper abdomen (epigastrium), shoulders, arms (upper and forearm), wrist, fingers, neck and throat, lower jaw and teeth (but not upper jaw), and not infrequently to the back (specifically the interscapular region) [9,10,14,22]. Pain radiating to the upper extremities, especially both arms, is highly suggestive of ischemic pain. Afferent nerves to the same segment of the spinal cord of the heart underlie referral of pain to other areas within the corresponding dermatomes (C5-6 and T1-T6). The radiation of angina is usually the same with each episode, except after bypass surgery due to the disruption of the neural innervation of the heart.

●Site – Ischemic pain is not felt in one specific spot; rather, it is a diffuse discomfort that may be difficult to localize. The patient often indicates the entire chest rather than localizing it to a specific area by pointing a single finger. Ischemic episodes are generally felt in the same location [23].

●Time course – Stable angina is usually brief (two to five minutes) and is relieved by rest or with nitroglycerin. In comparison, patients with an ACS may have chest pain at rest, and the duration is variable but generally lasts longer than 30 minutes. Classic anginal pain lasting more than 20 minutes suggests ACS. Continuous pain that does not wax and wane and persists for over 24 hours is unlikely to be due to ACS [24].

●Associated symptoms – Ischemic pain is often associated with other symptoms. The most common is shortness of breath, which may reflect mild pulmonary congestion resulting from ischemia-mediated diastolic dysfunction. Other symptoms may include belching, nausea, indigestion, vomiting, diaphoresis, dizziness, lightheadedness, clamminess, and fatigue.

Historical features increasing likelihood of ACS — Historical features that increase the likelihood of ACS include the following:

●Patients with a prior history of ACS have a significantly increased risk of recurrent ischemic events.

●A prior history of another vascular disease (eg, stroke, peripheral vascular disease) is associated with a risk of cardiac ischemic events comparable to that seen with a prior history of ACS.

●Risk factors for cardiovascular disease, particularly age, male sex, diabetes, hypertension, dyslipidemia, cigarette smoking, and family history of premature cardiovascular disease [25]. (See "Overview of established risk factors for cardiovascular disease".)

●Recent use of cocaine or other sympathomimetic drugs (eg, methamphetamine, cathinones) [26]. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine use" and "Methamphetamine: Acute intoxication" and "Acute amphetamine and synthetic cathinone ("bath salt") intoxication".)

Features of noncardiac chest pain — The following characteristics are more typical of nonischemic chest discomfort [9,27,28]:

●Pleuritic pain, sharp or knife-like pain related to respiratory movements or cough

●Primary or sole location in the mid or lower abdominal region

●Any discomfort localized with one finger

●Any discomfort reproduced by movement or palpation

●Constant pain lasting for days

●Fleeting pains lasting for a few seconds or less

●Pain radiating into the lower extremities or above the mandible (ie, "pain above the nose or below the navel is rarely cardiac in origin")

Some patients who appear to have a noncardiac cause of chest pain have other serious conditions including acute aortic dissection, pulmonary embolism, tension pneumothorax, myocarditis, perforating peptic ulcer, and esophageal rupture (table 2). It is essential to consider these alternate diagnoses to avoid potentially dangerous errors in management, such as the administration of antiplatelet, anticoagulant, or thrombolytic therapy to a patient with an aortic dissection. (See "Approach to the adult with nontraumatic chest pain in the emergency department".)

Atypical presentations — Some patients with ACS present with symptoms other than chest pain or chest pain that is "atypical" for ACS. For example, in the Multicenter Chest Pain Study, acute ischemia was diagnosed in 22 percent of patients who presented with sharp or stabbing pain and 13 percent who presented with pleuritic-type pain [27]. In a review of over 430,000 patients with confirmed acute myocardial infarction from the National Registry of Myocardial Infarction II, one-third had no chest pain on presentation to the hospital [29]. These patients often present with symptoms such as dyspnea alone, weakness, nausea and/or vomiting, epigastric pain or discomfort, palpitations, syncope, or cardiac arrest. They are more likely to be older, female, or have diabetes [10,29-31]. (See "Clinical features and diagnosis of coronary heart disease in women", section on 'Clinical presentation' and "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus", section on 'Silent ischemia and infarction'.)

The absence of chest pain has important implications for therapy and prognosis. In the Registry, compared with patients with chest pain, those without chest pain were less likely to be diagnosed with a confirmed myocardial infarction on admission (22 versus 50 percent), receive appropriate medical therapy, and receive thrombolysis or primary percutaneous coronary intervention (PCI; 25 versus 74 percent) [29]. Not surprisingly, these differences were associated with an increased in-hospital mortality (23.3 versus 9.3 percent, adjusted odds ratio [aOR] 2.21, 95% CI 2.17-2.26).

Examination findings — ACS is characterized by subtle examination findings or a normal examination. Ischemia impairs myocardial function, which may result in the following findings, but many patients have none of these features. Some patients may present with sudden cardiac arrest.

●Increase in heart rate – Increased reflex sympathetic nervous system activation can raise the heart rate, even if the patient is receiving a beta blocker or calcium channel blocker.

●Elevation in blood pressure – Ischemia often causes a hypertensive blood pressure response from sympathetic activation and stimulation of the left anterior descending coronary artery chemoreceptor.

●Skin findings – Diaphoresis, which occurs from sympathetic activation, is associated with increased likelihood of ACS [32]. Cool, clammy, pale, or ashen skin suggests systemic hypoperfusion.

●Evidence of heart failure or systemic hypoperfusion – Left-sided heart failure may cause pulmonary crackles and an S3 gallop. The presence of hypotension or impaired cognition suggests systemic hypoperfusion and cardiogenic shock. Jugular venous distention (movie 1), hepatojugular reflux, and peripheral edema suggest right-sided heart failure. Palpation of the left anterior chest wall at the anterior axillary line may reveal an abnormal tapping in systole, which reflects the presence of an area of dyskinetic left ventricular contraction or aneurysm. Transient right ventricular dysfunction may lead to a transient right ventricular heave or sternal pulsation. (See "Auscultation of heart sounds" and "Examination of the precordial pulsation" and "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial infarction", section on 'Clinical presentation'.)

●New heart sounds – Ischemia-induced myocardial dysfunction can lead to changes in the normal heart sounds. The second heart sound may become paradoxically split due to delayed relaxation of the left ventricular myocardium and delayed closure of the aortic valve. There may also be a third or fourth heart sound. (See "Auscultation of heart sounds".)

●New/changed murmurs – A new systolic murmur is an ominous sign that may signify papillary muscle dysfunction or a ventricular septal defect. Impaired myocardial function may result in a new mitral regurgitation murmur, causing apical tethering or tenting of the leaflets, or changes in the intensity or timing of preexisting murmurs. (See "Auscultation of cardiac murmurs in adults".)

INITIAL ASSESSMENT AND INTERVENTIONS — 

Patients presenting to the emergency department (ED) with chest pain or other symptoms possibly due to ACS (eg, dyspnea) should be rapidly evaluated for acute ischemia or another potentially life-threatening illness. If ACS is the leading diagnosis, initial assessment and interventions must be performed rapidly. (See 'History' above and "Approach to the adult with nontraumatic chest pain in the emergency department" and "Approach to the adult with dyspnea in the emergency department".)

General measures — During the initial phase, the following steps should be accomplished for any patient at significant risk for ACS (table 1):

●Assess responsiveness, airway, breathing, and circulation – In patients in respiratory or cardiorespiratory arrest, the appropriate resuscitation algorithms should be followed (algorithm 1 and algorithm 2 and algorithm 3). (See "Advanced cardiac life support (ACLS) in adults" and "Overview of advanced airway management in adults for emergency medicine and critical care".)

●Obtain preliminary history and examination – Obtain a brief history focused on ACS and other potentially life-threatening causes of chest pain, such as acute aortic dissection, pulmonary embolism, tension pneumothorax, perforating peptic ulcer, and esophageal rupture (table 2). (See 'History' above.)

If thrombolysis is considered as a potential therapy, inquire about potential contraindications (table 4) and perform a screening neurologic examination to assess for focal lesions or cognitive deficits. (See "Acute ST-elevation myocardial infarction: Management of fibrinolysis".)

The initial physical examination should focus on aiding immediate diagnosis and management and should include the following:

•Findings suggestive of ACS. (See 'Examination findings' above.)

•Evidence of systemic hypoperfusion (hypotension; tachycardia; impaired cognition; cool, clammy, pale, ashen skin) – Cardiogenic shock complicating acute myocardial infarction requires aggressive evaluation and management (table 5). (See "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial infarction" and "Treatment and prognosis of cardiogenic shock complicating acute myocardial infarction".)

•Evidence of heart failure (jugular venous distention, new or worsening pulmonary crackles, hypotension, tachycardia, new S3 gallop, new or worsening mitral regurgitation murmur) – In patients with acute myocardial infarction (AMI) complicated by heart failure, management depends on the severity of heart failure and the presence of contributing factors (eg, mechanical complications, preexisting valve disease). (See "Treatment of acute decompensated heart failure: Specific therapies" and "Acute myocardial infarction: Mechanical complications".)

•Features suggesting aortic dissection (abrupt onset tearing, sharp pain in the chest, abdomen, or back, asymmetric or absent proximal extremity or carotid pulses, new aortic valve murmurs) – Aortic dissection is an uncommon cause of ST-elevation myocardial infarction (STEMI) but requires management that is different from the typical management of STEMI. (See "Overview of acute aortic dissection and other acute aortic syndromes".)

●Interpret the twelve-lead ECG – The initial electrocardiogram (ECG) is often not diagnostic in patients with ACS. Thus, the ECG should be repeated at 15 to 30-minute intervals if the initial study is not diagnostic but the patient remains symptomatic and high clinical suspicion for ACS persists. ECG interpretation is discussed below. (See 'Electrocardiogram assessment' below.)

If the initial ECG reveals ST-elevation or equivalent, immediate intervention is required. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy" and "Acute ST-elevation myocardial infarction: Management of anticoagulation" and "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy".)

●Place patient on cardiac monitor – The patient should be placed on continuous heart rhythm monitoring, continuous pulse oximetry, and have frequent blood pressure measurements. Ensure emergency resuscitation equipment (including a defibrillator and airway equipment) is nearby.

●Establish intravenous access – Intravenous (IV) access should be established, and blood drawn for initial laboratory studies. (See 'Cardiac biomarkers and other laboratory testing' below.)

●Administer aspirin – All patients with suspected ACS should be given aspirin 162 to 325 mg to chew and swallow unless there is a compelling contraindication (eg, history of anaphylactic reaction, aortic dissection is suspected) or it has been taken prior to presentation. Despite its well-demonstrated benefit, aspirin remains underutilized in the setting of ACS. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Aspirin' and "Acute non-ST-elevation acute coronary syndromes: Initial antiplatelet therapy", section on 'Empiric antiplatelet therapy'.)

●Chest radiograph – Unless imaging will delay management of a STEMI, a chest radiograph should be obtained for patients with suspected ACS to evaluate for alternate etiologies (eg, pneumothorax) or complications (eg, pulmonary edema). (See "Approach to the adult with nontraumatic chest pain in the emergency department", section on 'Chest radiograph (most patients)'.)

Role of supplemental oxygen — Supplemental oxygen should be given as necessary to maintain oxygen saturation ≥94 percent. In patients with ACS with normal oxygen saturation and no signs of respiratory distress, we suggest not administering supplemental oxygen.

A meta-analysis (7 studies, 7702 patients) and Cochrane review found that the routine use of oxygen did not decrease the individual risks of all-cause death, recurrent ischemia or myocardial infarction (MI), heart failure, or occurrence of arrhythmia events [33,34].

Most of the patients in the meta-analysis were from the DETO2X-AMI registry-based trial, in which 6629 patients with suspected MI and oxygen saturation of 90 percent or higher were randomly assigned to receive either supplemental oxygen (6 L/min for 6 to 12 hours, delivered through an open face mask) or ambient air [35]. There were no differences in the rate of death from any cause within one year (5.0 versus 5.1 percent; hazard ratio [HR] 0.97, 95% CI 0.79-1.21) and the rate of rehospitalization with MI within one year (3.8 versus 3.3 percent; HR 1.13, 95% CI 0.88-1.46). During a median follow-up of 2.1 years, there was no difference in the rate of the composite end point of all-cause death, rehospitalization for MI, or hospitalization for heart failure (11.2 versus 10.8 percent; HR 1.02, 95% CI 0.88-1.17) [36].

Supplemental oxygen may be harmful in patients with normoxia because hyperoxia, which might occur with the administration of oxygen to normoxic individuals, has been shown to have a direct vasoconstrictor effect on the coronary arteries [37-40].

Symptomatic management

●Administer nitroglycerin if ongoing symptoms – In most cases of suspected ACS with ongoing symptoms, administer nitroglycerin 0.3 to 0.4 mg sublingual (SL) every five minutes for a total of three doses, after which an assessment of blood pressure and pain relief should guide the need for nitroglycerin IV. Nitrates can reduce the symptoms of chest discomfort and heart failure as well as treat hypertension. However, nitrates should be considered as symptomatic management since despite extensive clinical use and several large trials, a mortality benefit has not been demonstrated [41,42].

Contraindications to nitrates include severe aortic stenosis, hypertrophic cardiomyopathy, suspected right ventricular infarct, hypotension, marked bradycardia or tachycardia, and recent use of phosphodiesterase-5 (PDE-5) inhibitor. Prior to administering nitrates, all patients should be questioned about the use of a PDE-5 inhibitor, such as sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis); nitrates are contraindicated if these have been used in the last 24 hours (or perhaps as long as 48 hours with tadalafil) because of the propensity to cause potentially severe hypotension. (See "Nitrates in the management of acute coronary syndrome", section on 'Side effects and caution'.)

Extreme care should also be taken before giving nitrates in the setting of an inferior myocardial infarction with possible involvement of the right ventricle (waveform 1). In this setting, patients are dependent upon preload to maintain cardiac output, and nitrates can cause severe hypotension. (See "Right ventricular myocardial infarction".)

Nitrates relax smooth muscles and can relieve ischemic pain by dilating large coronary arteries and arterioles, dilating the venous system and decreasing preload, and to a lesser extent, decrease afterload by dilating systemic arteries [43]. The evidence that sublingual nitroglycerin relieves anginal symptoms is based on decades of clinical experience, observational data (including angiographic assessment), and some trials [44]. As an example, a trial of 52 patients found the oral nitroglycerin decreased the frequency and severity of anginal episodes by almost 50 percent [45]. Additionally, several small series and a trial (167 patients) have found that intravenous nitroglycerin reduced the frequency and duration of ischemic episodes with symptomatic improvement [46-48].

Nitroglycerin should not be given as a diagnostic test in patients with chest pain or a presentation that is not consistent with ACS since the response to treatment may cloud the clinical picture. Pain relief with nitroglycerin in an acute care setting is not helpful in distinguishing cardiac from noncardiac chest pain [15,19,49]. (See 'Ischemic chest pain' above.)

●Administer morphine only if needed for significant pain – Morphine (initial dose of 2 to 4 mg IV, with increments of 2 to 8 mg IV, repeated at 5 to 15-minute intervals) may be given for the relief of severe, persistent chest pain not relieved by other means, but should not be given routinely.

In a study of 57,039 patients with non-ST-elevation ACS (NSTEACS) enrolled in the CRUSADE Initiative, those treated with morphine (29.8 percent) had a higher adjusted risk of death (5.5 versus 4.7 percent, odds ratio 1.48, 95% CI 1.33-1.64) [50]. It is possible that patients receiving morphine had a higher baseline risk, but the CRUSADE study suggests caution in its use.

Morphine can reduce sympathetic stimulation caused by pain and anxiety, thereby decreasing cardiac workload and risks associated with excess catecholamines. However, morphine may worsen outcomes in patients with AMI by interfering with the antiplatelet effect of the P2Y₁₂ receptor blockers (eg, clopidogrel, ticagrelor, prasugrel) [51-53]. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes", section on 'Morphine' and "Overview of the acute management of ST-elevation myocardial infarction", section on 'Therapies of unclear benefit'.)

ELECTROCARDIOGRAM ASSESSMENT

Initial interpretation and criteria for ischemia — Specific approaches to patients judged to have definite or probable ACS based upon a targeted history and physical examination are initially guided by the accompanying 12-lead electrocardiogram (ECG) [54]. ECG interpretation for this purpose is discussed in detail separately; a focused review is provided below. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction" and "Diagnosis of acute myocardial infarction", section on 'ECG' and "ECG tutorial: Myocardial ischemia and infarction".)

The initial ECG is often not diagnostic in patients with ACS. Forty-one percent of patients with non-ST elevation myocardial infarction (NSTEMI) do not have the typical ST-depression or T-wave inversion [55]. In patients at intermediate to high risk for ACS without a clear diagnosis, ECGs should be repeated at frequent intervals until the patient's chest pain resolves or a definitive diagnosis is made. (See 'Importance of serial electrocardiograms' below.)

The following are criteria for the two major categories of ECG manifestations of acute myocardial ischemia (assuming the usual calibration of 1 mV/10 mm) (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'ECG criteria for myocardial ischemia/infarct'):

●Findings consistent with ST elevation myocardial infarction (STEMI) – New or presumed new ST-segment elevation at the J-point in two anatomically contiguous leads using the following thresholds:

•≥0.1 mV (≥1 mm) in all leads other than V2 to V3 (waveform 2 and waveform 3 and waveform 4 and waveform 5)

•For leads V2 to V3 (waveform 6 and waveform 7):

-≥0.2 mV (≥2 mm) in males ≥ 40 years

-≥0.25 mV (≥2.5 mm) in males <40 years

-≥0.15 mV (≥1.5 mm) in females

●Findings consistent with NSTEMI – Two anatomically contiguous leads with either or both of the following:

•New or presumed new horizontal or down-sloping ST depression ≥0.05 mV (≥0.5 mm)

•T wave inversion ≥0.1 mV (≥1 mm) with prominent R wave or R/S ratio >1

Other high-risk ECG findings, which may be STEMI-equivalents, include (see "Overview of the acute management of ST-elevation myocardial infarction", section on 'Rapid diagnosis of STEMI'):

●Newly identified left bundle branch block (waveform 8) (see 'Left bundle branch block or pacemaker' below)

●Horizontal ST-depression in leads V1 to V4 and relatively tall R-waves in leads V1 to V3 suggesting posterior wall STEMI (waveform 9) (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Posterior wall MI')

●Wellens pattern (deep T-wave inversions in multiple precordial leads) (waveform 10) (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Left anterior descending coronary T-wave inversion pattern')

●de Winter sign (tall, symmetric, T waves arising from upsloping ST-segment depression in leads V2 to V6 sometimes with ST-elevation in lead aVR) (figure 1) (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'de Winter sign')

Patients with inferior wall ischemia (ST-elevation in leads II, III, and aVF (waveform 4)) should have right-sided leads V4R, V5R, and V6R (figure 2) to assess for right ventricular infarction (waveform 1). Patients with prominent R waves and ST depressions in leads V1 and V2 (waveform 9) should have posterior leads V7, V8, and V9 (figure 3) to assess for posterior wall ST-elevation (waveform 11). (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'When to place nonstandard leads?'.)

The ECG leads are more helpful in localizing regions of transmural than subendocardial ischemia. The anatomic location of a transmural infarct is determined by which ECG leads show ST elevation and/or increased T wave positivity and is discussed separately. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Location of ischemia or infarction'.)

ECG abnormalities that appear to represent myocardial ischemia or infarction may be present for other reasons (table 6). However, an emergency department (ED) patient with symptoms consistent with ACS and an ECG showing ST-elevation or a potential STEMI-equivalent requires either immediate treatment for a STEMI or determination that the ST-elevation does not represent acute infarction (eg, identifying similar patterns on prior ECG, diagnosing pericarditis (table 7)). (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Differential diagnosis of ECG abnormalities'.)

Importance of serial electrocardiograms — If the initial ECG is not diagnostic but the patient remains symptomatic and clinical suspicion for ACS remains high, the ECG should be repeated at least every 15 to 30 minutes. An ECG obtained while the patient is experiencing chest pain that fails to show evidence of ischemia does not rule out the possibility of ACS [56,57]. Patients whose repeat ECGs are diagnostic for or strongly suggestive of either STEMI or NSTEMI should be managed for those diagnoses. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

In two series, the initial ECG was nondiagnostic in 45 percent and normal in 20 percent of patients subsequently shown to have an acute myocardial infarction (AMI) [4,58]. In the early hours of infarction, peaked, hyperacute T waves (waveform 12 and waveform 13) may be the only abnormality. Patients whose baseline ECG already shows abnormal T-wave inversions may develop paradoxical T-wave normalization (pseudonormalization) during episodes of acute transmural ischemia [59].

Left bundle branch block or pacemaker — Even though a newly identified left bundle branch block (LBBB) (waveform 14 and waveform 8) in a patient with symptoms of ACS may be a STEMI-equivalent (which is present in approximately 7 percent of patients with AMI), an existing LBBB typically causes ST-elevation and can interfere with the ECG diagnosis of coronary-related ischemia [60]. Since approximately one-half of patients with LBBB and an AMI do not have chest pain as a symptom of their ischemia, patients with LBBB are less likely to receive aspirin, beta blockers, and reperfusion therapy [61,62]. (See "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm", section on 'Left bundle branch block with mi'.)

Similar observations have been made in patients with a paced rhythm, which can also interfere with the ECG diagnosis of coronary-related ischemia [63]. (See "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm", section on 'Ventricular pacing'.)

Careful evaluation of the ECG may show some evidence of ACS in patients with these abnormalities, but the clinical history and cardiac biomarkers are of primary importance in this setting. The Sgarbossa criteria are specific but not sensitive for diagnosis of AMI; these are discussed separately. (See "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm", section on 'Sgarbossa criteria'.)

An emergently performed bedside echocardiogram (if available) may be helpful since severe ischemia produces regional wall motion abnormalities that can be visualized echocardiographically within seconds of coronary artery occlusion. (See "Role of echocardiography in acute myocardial infarction".)

CARDIAC BIOMARKERS AND OTHER LABORATORY TESTING — 

Obtain cardiac biomarkers (contemporary or high-sensitivity troponins), basic electrolyte concentrations, kidney function, and a complete blood count with platelets. Cardiac biomarkers should be obtained in any patient with concern for ACS; we prefer high-sensitivity troponin. Indices of coagulation should be obtained in patients at increased risk of coagulopathy due to anticoagulant use, a history of liver disease, or a history of excessive or spontaneous bleeding [64].

Serial cardiac biomarker testing, as well as use of a single high-sensitivity troponin to exclude ACS, is discussed separately. (See "Evaluation for suspected non-ST-segment elevation acute coronary syndromes", section on 'Management after initial testing'.)

Information on specific aspects of troponin testing, including high-sensitivity assays, sex-specific cutoffs, and chronic troponin elevation, is discussed separately. (See "Troponin testing: Clinical use".)

MANAGEMENT

ST-elevation MI — Selection and implementation of the optimal reperfusion strategy (algorithm 4) is the most important step in the management of patients with ST-elevation myocardial infarction (STEMI). Reperfusion therapy, whether percutaneous coronary intervention (PCI) or thrombolytics (table 8), should not await the result of cardiac biomarker measurement. Most patients should receive aspirin, an anticoagulant (algorithm 5), and a P2Y₁₂ inhibitor (prasugrel, ticagrelor, or clopidogrel); selection is determined by the reperfusion strategy and other patient characteristics. The accompanying table provides a concise summary of immediate treatment interventions (table 1). The management of patients with STEMI is discussed separately. (See "Overview of the acute management of ST-elevation myocardial infarction".)

Non-ST elevation ACS — Non-ST-elevation ACS (NSTEACS) was traditionally comprised of non-ST-elevation MI (NSTEMI) and unstable angina, which are distinguished by the presence of elevated serum biomarkers. The management of NSTEACS includes antiplatelet therapy (algorithm 6), anticoagulation (algorithm 7), and determination of early invasive strategy (eg, PCI) versus a conservative strategy with medical therapy (algorithm 8). Thrombolytic therapy should not be administered to patients with NSTEACS unless subsequent electrocardiograms (ECGs) develop ST segment elevations; thus, serial ECGs are essential. The accompanying table provides a concise summary of immediate treatment interventions (table 1). The management of patients with NSTEMI is discussed separately. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

Cardiac arrhythmias during ACS — Disturbances of cardiac rhythm during ACS are usually detected by cardiac monitor rather than by physical examination or 12-lead ECG:

●Sustained ventricular tachyarrhythmias in the peri-infarction period must be treated immediately because of their deleterious effect on cardiac output, possible exacerbation of myocardial ischemia, and the risk of deterioration into ventricular fibrillation (algorithm 1). (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".)

●While supraventricular tachyarrhythmias in the peri-infarction period may pose less immediate risk of cardiac arrest, the management of such arrhythmias is important because any tachycardia can increase myocardial oxygen demand, thereby exacerbating ischemia and possibly decreasing cardiac output (algorithm 3). (See "Supraventricular arrhythmias after myocardial infarction".)

●Bradyarrhythmias occurring early in the setting of an inferior wall myocardial infarction (within the first 24 hours) may respond to treatment with atropine (algorithm 2). Later bradyarrhythmias, wide QRS-complex bradyarrhythmias, and those occurring in the setting of an anterior wall myocardial infarction may require temporary pacemaker placement. (See "Conduction abnormalities after myocardial infarction".)

DISPOSITION — 

Patients with ACS are typically admitted to an intensive care unit, coronary care unit, or monitored cardiac unit depending upon the persistence of symptoms and evidence of hemodynamic compromise. Those with persistent pain or hemodynamic compromise generally undergo urgent angiography and revascularization. Others with resolution of symptoms and stable hemodynamics are typically admitted for early elective angiography and revascularization if appropriate. The patient's hemodynamic status, serum biomarkers, and historical risk factors, as well as available hospital resources, should also be used to determine appropriate disposition. Cardiology consultation is generally useful for any case in which the diagnosis, treatment plan, or disposition are unclear.

Patients with an uncertain diagnosis after initial assessment require further observation and evaluation. The management of such patients, including the use of validated ACS risk stratification tools (eg, HEART score) and noninvasive imaging for obstructive coronary artery disease (ie, rest imaging and stress testing), is discussed separately. (See "Evaluation for suspected non-ST-segment elevation acute coronary syndromes" and "Noninvasive imaging for diagnosis in patients at low to intermediate risk for acute coronary syndrome".)

IMPACT OF MISSED DIAGNOSIS — 

With careful evaluation using effective risk scores, serial electrocardiogram (ECGs), and appropriate diagnostic testing, only a very small percentage of patients with an acute coronary syndrome (ACS) are mistakenly discharged from the emergency department (ED) [65,66]. However, patients whose diagnosis is missed initially have an increase in short-term mortality [30,65,67,68]. For example, in a review of 10,689 Black, White, and Hispanic American patients who presented to the ED with symptoms suggesting ACS, 8 percent had an acute myocardial infarction (AMI), and 9 percent had unstable angina [30]. Among the patients with an ACS, 2.2 percent were mistakenly discharged from the ED. Atypical presentation most frequently led to missed diagnosis. The patients with missed myocardial infarction had the following characteristics:

●Females less than 55 years of age

●Non-White Americans

●Shortness of breath as the major presenting symptom

●Normal or nondiagnostic ECG

Misreading the ECG was an infrequent problem. There was a nonsignificant trend toward an increased risk-adjusted 30-day mortality ratio for patients who were not hospitalized (1.9 and 1.7 in the patients with myocardial infarction and unstable angina, respectively). While improvements in care since the publication of this study have reduced the rate of missed ACS in the ED, lessons about which patient groups are most at risk bear remembering.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST-elevation myocardial infarction (STEMI)" and "Society guideline links: Adult with chest pain in the emergency department".)

SUMMARY AND RECOMMENDATIONS

●Definitions and diagnosis – Acute coronary syndrome (ACS) applies to patients with myocardial ischemia or infarction. ACS can be further classified into ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTEACS). The latter was traditionally comprised of non-ST-elevation MI (NSTEMI) and unstable angina. (See "Acute coronary syndrome: Terminology and classification".)

The diagnosis of ACS/myocardial infarction (MI) depends upon the characteristics of the chest pain (if present), specific associated symptoms, electrocardiogram (ECG) abnormalities, and levels of serum markers of cardiac injury (ie, troponin). MI is characterized by a typical rise or fall in serum troponin. (See "Diagnosis of acute myocardial infarction".)

●Initial ECG obtained rapidly – The initial ECG should be obtained within 10 minutes of presentation but is often not diagnostic in patients with ACS. In patients without a clear diagnosis but at risk for ACS, ECGs should be repeated at frequent intervals (every 15 to 30 minutes) until the patient's chest pain resolves or a definitive diagnosis is made. (See 'Standing orders for initial rapid ECG' above and 'Electrocardiogram assessment' above.)

●Immediate assessment and interventions – If ACS is suspected, initial assessment and interventions must be performed rapidly to minimize potential injury to the myocardium (table 1), including the following (see 'Initial assessment and interventions' above):

•Assess airway, breathing, and circulation.

•Obtain preliminary history and examination.

•Interpret 12-lead ECG.

•Attach cardiac monitor to the patient and ensure resuscitation equipment is nearby.

•Establish intravenous (IV) access and obtain blood work (including contemporary or high-sensitivity troponin).

•Unless imaging will delay management of a STEMI, obtain a chest radiograph to evaluate for alternate etiologies (eg, pneumothorax) or complications (eg, pulmonary edema).

•Administer aspirin 162 to 325 mg to chew and swallow unless there is a compelling contraindication (eg, history of anaphylactic reaction) or it has been taken prior to presentation. The evidence is discussed separately. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Aspirin'.)

•In a patient with suspected ACS with ongoing symptoms, we suggest nitrates rather than morphine (Grade 2C). Administer nitroglycerin 0.3 to 0.4 mg sublingual (SL) every five minutes for a total of three doses. Contraindications include severe aortic stenosis, hypertrophic cardiomyopathy, suspected right ventricular infarct, hypotension, marked bradycardia or tachycardia, and recent use of phosphodiesterase-5 (PDE-5) inhibitor. Nitrates should be considered as symptomatic management since despite extensive clinical use, a mortality benefit has not been demonstrated. (See 'Symptomatic management' above.)

•We do not routinely treat pain from ACS with morphine. Morphine may increase risk of death in patients with NSTEACS but can be given for the relief of severe, persistent chest pain not relieved by nitrates or other means. (See 'Symptomatic management' above.)

•In a patient with suspected ACS who has an oxygen saturation ≥94 percent and no signs of respiratory distress, we suggest not administering supplemental oxygen (Grade 2C). Routine use of supplemental oxygen has not demonstrated a benefit and may be harmful in patients with normoxia since hyperoxia has a vasoconstrictor effect on the coronary arteries. (See 'Role of supplemental oxygen' above.)

●Characteristics of ischemic chest pain – Pain from coronary-related ischemia is more often characterized as non-focal chest discomfort or pressure rather than pain, is generally gradual in onset, and is exacerbated by activity. Symptoms associated with the highest relative risk of myocardial infarction include radiation to an upper extremity, particularly when there is radiation to both arms, and pain associated with diaphoresis, nausea, or vomiting. (See 'Ischemic chest pain' above.)

Many patients with ACS present with symptoms such as dyspnea or malaise, either alone or in addition to chest pain. Females are more likely to have associated dyspnea than males, and patients who are older or have diabetes are more likely to present with dyspnea without chest pain. Relief of symptoms following the administration of therapeutic interventions (eg, nitroglycerin, "gastrointestinal cocktail" of viscous lidocaine and antacid) does not reliably distinguish nonischemic from ischemic chest pain. (See 'History' above and 'Atypical presentations' above.)

●Differential diagnosis of chest pain – Chest discomfort can be caused by a number of life-threatening conditions (table 2) and premature diagnosis of ACS must be avoided. The evaluation of chest pain in the emergency department is discussed separately. (See "Approach to the adult with nontraumatic chest pain in the emergency department".)

●Further management and disposition – ECG findings, cardiac biomarkers, risk factors, persistence of symptoms, and evidence of hemodynamic compromise determine further management and disposition. In a patient with a STEMI, reperfusion therapy, whether percutaneous coronary intervention (PCI) or thrombolytics, should not await the result of cardiac biomarker measurement. (See 'Management' above and 'Disposition' above.)

With careful evaluation using appropriate risk scores and diagnostic testing, only a small percentage of patients with an ACS are mistakenly discharged from the ED, but these patients have an increase in short-term mortality. American patients whose ACS was missed are more likely to be females less than 55 years of age, non-White Americans, patients with shortness of breath as the major presenting symptom, and patients with a normal or nondiagnostic initial ECG. The subsequent management (ie, "rule out MI") of patients judged to be at low or intermediate risk for ACS after the initial ED evaluation is discussed separately. (See 'Impact of missed diagnosis' above and "Evaluation for suspected non-ST-segment elevation acute coronary syndromes".)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Eric Awtry, MD, who contributed to an earlier version of this topic review.