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Acute Myocardial Infarction (MI)
Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis. Diagnosis is by ECG and the presence or absence of serologic markers. Treatment is antiplatelet drugs, anticoagulants, nitrates, beta-blockers, statins, and reperfusion therapy. For ST-segment-elevation myocardial infarction, emergency reperfusion is via fibrinolytic drugs, percutaneous intervention, or, occasionally, coronary artery bypass graft surgery. For non-ST-segment-elevation MI, reperfusion is via percutaneous intervention or coronary artery bypass graft surgery.
(See also Overview of Acute Coronary Syndromes.)
In the US, about 1.5 million myocardial infarctions occur annually. MI results in death for 400,000 to 500,000 people, with about half dying before they reach the hospital (see Cardiac Arrest).
Acute myocardial infarction (MI), along with unstable angina, is considered an acute coronary syndrome. Acute MI includes both non ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). Distinction between NSTEMI and STEMI is vital as treatment strategies are different for these two entities.
Myocardial infarction is defined as myocardial necrosis in a clinical setting consistent with myocardial ischemia ( 1). These conditions can be satisfied by a rise of cardiac biomarkers (preferably cardiac troponin [cTn]) above the 99th percentile of the upper reference limit (URL) plus at least one of the following:
Slightly different criteria are used to diagnose MI during and after percutaneous coronary intervention or coronary artery bypass grafting, and as the cause of sudden death.
MI also can be classified into 5 types based on etiology and circumstances:
Type 1: Spontaneous MI caused by ischemia due to a primary coronary event (eg, plaque rupture, erosion, or fissuring; coronary dissection)
Type 2: Ischemia due to increased oxygen demand (eg, hypertension), or decreased supply (eg, coronary artery spasm or embolism, arrhythmia, hypotension)
Type 3: Related to sudden unexpected cardiac death
Type 4a: Associated with percutaneous coronary intervention (signs and symptoms of myocardial infarction with cTn values > 5 × 99th percentile URL)
Type 4b: Associated with documented stent thrombosis
Type 5: Associated with coronary artery bypass grafting (signs and symptoms of myocardial infarction with cTn values >10 × 99th percentile URL)
MI affects predominantly the left ventricle (LV), but damage may extend into the right ventricle (RV) or the atria. RV infarction usually results from obstruction of the right coronary or a dominant left circumflex artery; it is characterized by high RV filling pressure, often with severe tricuspid regurgitation and reduced cardiac output. An inferoposterior infarction causes some degree of RV dysfunction in about half of patients and causes hemodynamic abnormality in 10 to 15%. RV dysfunction should be considered in any patient who has inferoposterior infarction and elevated jugular venous pressure with hypotension or shock. RV infarction complicating LV infarction significantly increases mortality risk.
Anterior infarcts tend to be larger and result in a worse prognosis than inferoposterior infarcts. They are usually due to left coronary artery obstruction, especially in the anterior descending artery; inferoposterior infarcts reflect right coronary or dominant left circumflex artery obstruction.
Infarction may be
Transmural infarcts involve the whole thickness of myocardium from epicardium to endocardium and are usually characterized by abnormal Q waves on ECG. Nontransmural or subendocardial infarcts do not extend through the ventricular wall and cause only ST-segment and T-wave (ST-T) abnormalities. Subendocardial infarcts usually involve the inner one third of myocardium, where wall tension is highest and myocardial blood flow is most vulnerable to circulatory changes. These infarcts may follow prolonged hypotension. Because the transmural depth of necrosis cannot be precisely determined clinically, infarcts are usually classified as STEMI or NSTEMI by the presence or absence of ST-segment elevation or Q waves on the ECG. Volume of myocardium destroyed can be roughly estimated by the extent and duration of CK elevation or by peak levels of more commonly measured troponins.
Non–ST-segment elevation myocardial infarction (NSTEMI, subendocardial MI) is myocardial necrosis (evidenced by cardiac markers in blood; troponin I or troponin T and CK will be elevated) without acute ST-segment elevation. ECG changes such as ST-segment depression, T-wave inversion, or both may be present.
ST-segment elevation myocardial infarction (STEMI, transmural MI) is myocardial necrosis with ECG changes showing ST-segment elevation that is not quickly reversed by nitroglycerin. Cardiac markers, troponin I or troponin T, and CK are elevated.
1. Thygesen K, Alpert JS, Jaffe AS, et al. the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction: ESC/ACCF/AHA/WHF Expert Consensus Document Third Universal Definition of Myocardial Infarction. Circulation 126:2020–2035, 2012. doi: 10.1161/CIR.0b013e31826e1058
Symptoms of NSTEMI and STEMI are the same. Days to weeks before the event, about two thirds of patients experience prodromal symptoms, including unstable or crescendo angina, shortness of breath, and fatigue.
Usually, the first symptom of infarction is deep, substernal, visceral pain described as aching or pressure, often radiating to the back, jaw, left arm, right arm, shoulders, or all of these areas. The pain is similar to angina pectoris but is usually more severe and long-lasting; more often accompanied by dyspnea, diaphoresis, nausea, and vomiting; and relieved little or only temporarily by rest or nitroglycerin. However, discomfort may be mild; about 20% of acute MIs are silent (ie, asymptomatic or causing vague symptoms not recognized as illness by the patient), more commonly in patients with diabetes. Patients often interpret their discomfort as indigestion, particularly because spontaneous relief may be falsely attributed to belching or antacid consumption.
Some patients present with syncope.
Women are more likely to present with atypical chest discomfort. Elderly patients may report dyspnea more than ischemic-type chest pain. In severe ischemic episodes, the patient often has significant pain and feels restless and apprehensive. Nausea and vomiting may occur, especially with inferior MI. Dyspnea and weakness due to LV failure, pulmonary edema, shock, or significant arrhythmia may dominate.
Skin may be pale, cool, and diaphoretic. Peripheral or central cyanosis may be present. Pulse may be thready, and BP is variable, although many patients initially have some degree of hypertension during pain.
Heart sounds are usually somewhat distant; a 4th heart sound is almost universally present. A soft systolic blowing apical murmur (reflecting papillary muscle dysfunction) may occur. During initial examination, a friction rub or more striking murmurs suggest a preexisting heart disorder or another diagnosis. Detection of a friction rub within a few hours after onset of MI symptoms suggests acute pericarditis rather than MI. However, friction rubs, usually evanescent, are common on days 2 and 3 post-STEMI. The chest wall is tender when palpated in about 15% of patients.
In right ventricular (RV) infarction, signs include elevated RV filling pressure, distended jugular veins (often with Kussmaul sign), clear lung fields, and hypotension.
Serial cardiac markers
Immediate coronary angiography (unless fibrinolytics are given) for patients with STEMI or complications (eg, persistent chest pain, hypotension, markedly elevated cardiac markers, unstable arrhythmias)
Delayed coronary angiography (within 24 to 48 h) for patients with NSTEMI without complications
(See also algorithm Approach to Acute Myocardial Infarction.)
Evaluation begins with initial and serial ECG and serial measurements of cardiac markers to help distinguish between unstable angina, ST segment elevation myocardial infarction, and non ST segment elevation myocardial infarction. This distinction is the center of the decision pathway because fibrinolytics benefit patients with STEMI but may increase risk for those with NSTEMI. Also, urgent cardiac catheterization is indicated for patients with acute STEMI but not generally for those with NSTEMI.
ECG is the most important test and should be done within 10 min of presentation.
For STEMI, initial ECG is usually diagnostic, showing ST-segment elevation ≥ 1 mm in 2 or more contiguous leads subtending the damaged area (see Figure: Acute lateral left ventricular infarction (tracing obtained within a few hours of onset of illness)., Lateral left ventricular infarction (after the first 24 h)., Lateral left ventricular infarction (several days later)., Acute inferior (diaphragmatic) left ventricular infarction (tracing obtained within a few hours of onset of illness)., Inferior (diaphragmatic) left ventricular infarction (after the first 24 h)., and Inferior (diaphragmatic) left ventricular infarction (several days later).).
Pathologic Q waves are not necessary for the diagnosis. The ECG must be read carefully because ST-segment elevation may be subtle, particularly in the inferior leads (II, III, aVF); sometimes the reader’s attention is mistakenly focused on leads with ST-segment depression. If symptoms are characteristic, ST-segment elevation on ECG has a specificity of 90% and a sensitivity of 45% for diagnosing MI. Serial tracings (obtained every 8 h for 1 day, then daily) showing a gradual evolution toward a stable, more normal pattern or development of abnormal Q waves over a few days tends to confirm the diagnosis.
If right ventricular (RV) infarction is suspected, a 15-lead ECG is usually recorded; additional leads are placed at V4-6R, and, to detect posterior infarction, V8 and V9.
ECG diagnosis of MI is more difficult when a left bundle branch block configuration is present because it resembles STEMI changes. ST-segment elevation concordant with the QRS complex strongly suggests MI as does > 5-mm ST-segment elevation in at least 2 precordial leads. But generally, any patient with suggestive symptoms and new-onset (or not known to be old) left bundle branch block is treated as for STEMI.
Cardiac markers (serum markers of myocardial cell injury) are cardiac enzymes (eg, CK-MB) and cell contents (eg, troponin I, troponin T, myoglobin) that are released into the bloodstream after myocardial cell necrosis. The markers appear at different times after injury, and levels decrease at different rates. Sensitivity and specificity for myocardial cell injury vary significantly among these markers, but the troponins (cTn) are the most sensitive and specific and are now the markers of choice. Recently, several new, highly sensitive assays of cardiac troponin (hs-cTn) that are also very precise have become available. These assays can reliably measure Tn levels (T or I) as low as 0.003 to 0.006 ng/mL (3 to 6 pg/mL); some research assays go as low as 0.001 ng/mL (1 pg/mL).
Previous, less sensitive cTn tests were unlikely to detect Tn except in patients who had an acute cardiac disorder. Thus a "positive" Tn (ie, above the limit of detection) was very specific. However, the new hs-cTn tests can detect small amounts of Tn in many healthy people. Thus, hs-cTn levels need to be referenced to the normal range, and are defined as "elevated" only when higher than 99% of the reference population. Furthermore, although an elevated troponin level indicates myocardial cell injury, it does not indicate the cause of the damage (although any troponin elevation increases the risk of adverse outcomes in many disorders). In addition to acute coronary syndrome (ACS), many other cardiac and non-cardiac disorders can elevate hs-cTn levels (see Table: Causes of Elevated Troponin); not all elevated hs-cTn levels represent MI, and not all myocardial necrosis results from an acute coronary syndrome event even when the etiology is ischemic. However, by detecting lower levels of Tn, hs-cTn assays enable earlier identification of MI than other assays, and have replaced other cardiac marker tests in many centers.
Patients suspected of having a myocardial infarction should have an hs-cTn level done on presentation and 3 h later (at 0 and 6 h if using a standard Tn assay).
An hs-cTn level must be interpreted based on the patient's pre-test probability of disease, which is estimated clinically based on:
A high pre-test probability plus an elevated hs-cTn level is highly suggestive of myocardial infarction, whereas a low pre-test probability plus a normal hs-cTn is unlikely to represent myocardial infarction. Diagnosis is more challenging when test results are discordant with pre-test probability, in which case serial hs-cTn levels often help. A patient with low pre-test probability and an initially slightly elevated hs-cTn that remains stable on repeat testing probably has non-ACS cardiac disease (eg, heart failure, stable coronary artery disease). However, if the repeat level rises significantly (ie, > 20 to 50%) the likelihood of myocardial infarction becomes much higher. If a patient with high pre-test probability has a normal hs-cTn level that rises > 50% when the hs-cTc is re-measured, myocardial infarction is likely; continued normal levels (often including at 6 h and beyond when suspicion is high) suggest need to pursue an alternate diagnosis.
Coronary angiography most often combines diagnosis with percutaneous coronary intervention (PCI—ie, angioplasty, stent placement). When possible, emergency coronary angiography and PCI are done as soon as possible after the onset of acute MI (primary PCI). In many tertiary centers, this approach has significantly lowered morbidity and mortality and improved long-term outcomes. Frequently, the infarction is actually aborted when the time from pain to PCI is short (< 3 to 4 h).
Angiography is obtained urgently for patients with STEMI, patients with persistent chest pain despite maximal medical therapy, and patients with complications (eg, markedly elevated cardiac markers, presence of cardiogenic shock, acute mitral regurgitation, ventricular septal defect, unstable arrhythmias). Patients with uncomplicated NSTEMI whose symptoms have resolved typically undergo angiography within the first 24 to 48 h of hospitalization to detect lesions that may require treatment.
After initial evaluation and therapy, coronary angiography may be used in patients with evidence of ongoing ischemia (ECG findings or symptoms), hemodynamic instability, recurrent ventricular tachyarrhythmias, and other abnormalities that suggest recurrence of ischemic events. Some experts also recommend that angiography be done before hospital discharge in STEMI patients with inducible ischemia on stress imaging or an ejection fraction < 40%.
Global risk should be estimated via formal clinical risk scores (Thrombosis in Myocardial Infarction [TIMI] or a combination of the following high-risk features:
Recurrent angina/ischemia at rest or during low-level activity
Worsening mitral regurgitation
High-risk stress test result (test stopped in ≤ 5 min due to symptoms, marked ECG abnormalities, hypotension, or complex ventricular arrhythmias)
Sustained ventricular tachycardia
PCI within past 6 mo
LV ejection fraction < 0.40
Overall mortality rate is about 30%, with 25 to 30% of these patients dying before reaching the hospital (typically due to ventricular fibrillation). In-hospital mortality rate is about 10% (typically due to cardiogenic shock) but varies significantly with severity of left ventricular failure (see Table: Killip Classification and Mortality Rate of Acute Myocardial Infarction*).
For patients receiving reperfusion (fibrinolysis or PCI), in-hospital mortality is 5 to 6%, versus 15% for patients eligible for reperfusion who do not receive reperfusion therapy. In centers with established primary PCI programs, in-hospital mortality is reported to be < 5%.
Most patients who die of cardiogenic shock have an infarct or a combination of scar and new infarct affecting ≥ 50% of LV mass. Five clinical characteristics predict 90% of the mortality in patients who present with STEMI (see Table: Mortality Risk at 30 Days in STEMI): older age (31% of total mortality), lower systolic BP (24%), Killip class > 1 (15%), faster heart rate (12%), and anterior location (6%). Mortality rates of women and patients with diabetes tend to be higher.
Mortality rate of patients who survive initial hospitalization is 8 to 10% in the year after acute MI. Most fatalities occur in the first 3 to 4 mo. Persistent ventricular arrhythmia, heart failure, poor ventricular function, and recurrent ischemia indicate high risk. Many authorities recommend stress ECG before hospital discharge or within 6 wk. Good exercise performance without ECG abnormalities is associated with a favorable prognosis; further evaluation is usually not required. Poor exercise performance is associated with a poor prognosis.
Cardiac performance after recovery depends largely on how much functioning myocardium survives the acute attack. Acute damage adds to scars from previous infarcts. When > 50% of left ventricular mass is damaged, prolonged survival is unusual.
Killip Classification and Mortality Rate of Acute Myocardial Infarction*
Mortality Risk at 30 Days in STEMI
Risk of Adverse Events* at 14 Days in NSTEMI
Prehospital care: oxygen, aspirin, nitrates and/or opioids for pain, and triage to an appropriate medical center
Drug treatment: Antiplatelet drugs, antianginal drugs, anticoagulants, and in some cases other drugs
Reperfusion therapy: Fibrinolytics or angiography with percutaneous coronary intervention or coronary artery bypass surgery
Postdischarge rehabilitation and chronic medical management of coronary artery disease
A reliable IV route must be established, oxygen given (typically 2 L by nasal cannula), and continuous single-lead ECG monitoring started. Prehospital interventions by emergency medical personnel (including ECG, chewed aspirin [325 mg], pain management (with nitrates or opioids) can reduce risk of mortality and complications. Early diagnostic data and response to treatment can help determine the need for and timing of revascularization.
On arrival to the emergency room, the patient's diagnosis is confirmed. Drug therapy and timing of revascularization depend on the clinical picture and diagnosis.
For STEMI, reperfusion strategy can include fibrinolytic therapy or immediate PCI. For patients with NSTEMI, angiography may be done within 24 to 48 h of admission if the patient is clinically stable. If the patient is unstable (eg, ongoing symptoms, hypotension or sustained arrhythmias), then angiography must be done immediately (see Figure: Approach to myocardial infarction.).
Approach to myocardial infarction.
All patients should be given antiplatelet drugs, anticoagulants, and if chest pain is present, antianginal drugs. The specific drugs used depend on the reperfusion strategy and other factors; their selection and use is discussed in Drugs for Acute Coronary Syndrome. Other drugs, such as beta-blockers, ACE inhibitors, and statins, should be initiated during admission (see Table: Drugs for Coronary Artery Disease*).
Patients with acute myocardial infarction should be given the following (unless contraindicated):
Antiplatelet drugs: Aspirin, clopidogrel, or both (prasugrel or ticagrelor are alternatives to clopidogrel)
Anticoagulants: A heparin (unfractionated or low molecular weight heparin) or bivalirudin
Glycoprotein IIb/IIIa inhibitor for some high risk patients
Antianginal therapy usually nitroglycerin
All patients are given aspirin 160 to 325 mg (not enteric-coated), if not contraindicated, at presentation and 81 mg once/day indefinitely thereafter. Chewing the first dose before swallowing quickens absorption. Aspirin reduces short-term and long-term mortality risk. In patients undergoing PCI, a loading dose of clopidogrel (300 to 600 mg po once), prasugrel (60 mg po once), or ticagrelor (180 mg po once) improves outcomes, particularly when administered 24 h in advance. For urgent PCI, prasugrel and ticagrelor are more rapid in onset and may be preferred.
Either a low molecular weight heparin (LMWH), unfractionated heparin, or bivalirudin is given routinely to patients with unstable angina unless contraindicated (eg, by active bleeding). Unfractionated heparin is more complicated to use because it requires frequent (q 6 h) dosing adjustments to achieve target activated PTT (aPTT). The LMWHs have better bioavailability, are given by simple weight-based dose without monitoring aPTT and dose titration, and have lower risk of heparin-induced thrombocytopenia. Bivalirudin is recommended for those with a known or suspected history of heparin-induced thrombocytopenia.
Consider glycoprotein IIb/IIIa inhibitor for high risk patients (patients with recurrent ischemia, dynamic ECG changes or hemodynamic instability). Abciximab, tirofiban, and eptifibatide appear to have equivalent efficacy, and the choice of drug should depend on other factors (eg, cost, availability, familiarity).
Chest pain can be treated with morphine or nitroglycerin. Morphine 2 to 4 mg IV, repeated q 15 min as needed, is highly effective but can depress respiration, can reduce myocardial contractility, and is a potent venous vasodilator. Hypotension and bradycardia secondary to morphine can usually be overcome by prompt elevation of the lower extremities. Nitroglycerin is initially given sublingually, followed by continuous IV drip if needed.
Standard therapy for all patients with unstable angina includes beta-blockers, ACE inhibitors, and statins. Beta-blockers are recommended unless contraindicated (eg, by bradycardia, heart block, hypotension, or asthma), especially for high-risk patients. Beta-blockers reduce heart rate, arterial pressure, and contractility, thereby reducing cardiac workload and oxygen demand. ACE inhibitors may provide long-term cardioprotection by improving endothelial function. If an ACE inhibitor is not tolerated because of cough or rash (but not angioedema or renal dysfunction), an angiotensin II receptor blocker may be substituted. Statins are also standard therapy and should be continued indefinitely.
For STEMI patients, emergency PCI is the preferred treatment of ST-segment elevation myocardial infarction when available in a timely fashion (door to balloon-inflation time < 90 min) by an experienced operator. If there is likely to be a significant delay in availability of PCI, thrombolysis should be done for STEMI patients meeting criteria (see Table: Infarct extent). Reperfusion using fibrinolytics is most effective if given in the first few minutes to hours after onset of myocardial infarction. The earlier a fibrinolytic is begun, the better. The goal is a door-to-needle time of 30 to 60 min. Greatest benefit occurs within 3 h, but the drugs may be effective up to 12 h. Characteristics and selection of fibrinolytic drugs are discussed elsewhere.
Unstable NSTEMI patients (ie, those with ongoing symptoms, hypotension, or sustained arrhythmias) should proceed directly to the cardiac catheterization laboratory to identify coronary lesions requiring PCI or CABG. Immediate reperfusion is not as urgent in patients with uncomplicated NSTEMI, in whom a completely occluded infarct-related artery at presentation is uncommon. Such patients typically undergo angiography within the first 24 to 48 h of hospitalization to identify coronary lesions requiring PCI or CABG. Fibrinolytics are not indicated for NSTEMI. Risk outweighs potential benefit.
Choice of reperfusion strategy is further discussed in Revascularization for Acute Coronary Syndromes.
Patients who did not have coronary angiography during admission, have no high-risk features (eg, heart failure, recurrent angina, ventricular tachycardia or ventricular fibrillation after 24 h, mechanical complications such as new murmurs, shock), and have an ejection fraction > 40% whether or not they received fibrinolytics usually should have stress testing of some sort before or shortly after discharge (see Table: Functional Evaluation After MI).
Functional Evaluation After MI
The acute illness and treatment of myocardial infarction should be used to strongly motivate the patient to modify risk factors. Evaluating the patient’s physical and emotional status and discussing them with the patient, advising about lifestyle (eg, smoking, diet, work and play habits, exercise), and aggressively managing risk factors may improve prognosis.
On discharge, all patients should be on appropriate antiplatelet drugs, statins, antianginals, and other drugs based on comorbidities.
Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery.
Symptoms of acute myocardial infarction include chest pain or discomfort with or without dyspnea, nausea, and diaphoresis.
Women and patients with diabetes are more likely to present with atypical symptoms, and 20% of acute MI are silent.
Diagnosis is by ECG and cardiac markers.
Immediate treatment includes oxygen, antianginals, antiplatelet drugs, and anticoagulants.
For patients with STEMI, do immediate angiography with percutaneous coronary intervention (PCI); if immediate PCI is not available, give fibrinolytics.
For patients with NSTEMI who are stable, do angiography within 24 to 48 h; for those who are unstable, do immediate angiography with PCI.
Following recovery, initiate or continue antiplatelet drugs, beta-blockers, ACE inhibitors, and statins.
Drug NameSelect Trade
aspirinNo US brand name
morphineDURAMORPH PF, MS CONTIN
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