Acute Myocardial Infarction (MI)

MI affects predominantly the left ventricle (LV), but damage may extend into the right ventricle (RV) or the atria.

Right ventricular 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 Tricuspid Regurgitation Tricuspid regurgitation (TR) is insufficiency of the tricuspid valve causing blood flow from the right ventricle to the right atrium during systole. The most common cause is dilation of the... read more 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 (including 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 cardiac troponins.

Non–ST-segment elevation myocardial infarction (NSTEMI, subendocardial MI) is myocardial necrosis (evidenced by cardiac markers Cardiac markers Acute coronary syndromes result from acute obstruction of a coronary artery. Consequences depend on degree and location of obstruction and range from unstable angina to non–ST-segment elevation... read more 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. Troponin I or troponin T and CK are elevated.

Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is found in about 5 to 6% of patients with acute MI who undergo coronary angiography (2 Pathophysiology references Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more ). Patients with MINOCA tend to be younger, women, and without dyslipidemia. They tend to have myocardial necrosis without significant coronary atherosclerosis. Plaque disruption and coronary vasospasm are common in MINOCA. Coronary thrombosis or embolism and spontaneous coronary artery dissection are causes of MINOCA. Medical management should be based on the underlying mechanism for MINOCA in each patient.

ECG Electrocardiography The standard electrocardiogram (ECG) provides 12 different vector views of the heart’s electrical activity as reflected by electrical potential differences between positive and negative electrodes... read more is the most important test and should be done as soon as possible (eg,within 10 minutes 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 figures Acute lateral left ventricular infarction Acute lateral left ventricular infarction (tracing obtained within a few hours of onset of illness) , Lateral left ventricular infarction Lateral left ventricular infarction (after the first 24 hours) , Lateral left ventricular infarction (several days later) Lateral left ventricular infarction (several days later) , Acute inferior (diaphragmatic) left ventricular infarction Acute inferior (diaphragmatic) left ventricular infarction (tracing obtained within a few hours of onset of illness) , Inferior (diaphragmatic) left ventricular infarction Inferior (diaphragmatic) left ventricular infarction (after the first 24 hours) , and Inferior (diaphragmatic) left ventricular infarction (several days later) 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 myocardial infarction. Serial tracings (obtained every 8 hours 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, creatine kinase-MB isoenzyme [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 the markers of choice. Several highly sensitive assays of cardiac troponin (hs-cTn) that are also very precise are available. These assays can reliably measure cTn 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 methods of measuring cTn were unlikely to detect cTn except in patients who had an acute cardiac disorder. Thus a "positive" cTn result (ie, above the limit of detection) was very specific. However, the hs-cTn tests can detect small amounts of cTn 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 cTn level indicates myocardial cell injury, it does not indicate the cause of the damage (although any cTn 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 cause the hs-cTn measurement to be elevated (see table ); not all elevated hs-cTn measurements represent myocardial infarction, and not all myocardial necrosis results from an acute coronary syndrome event even when the etiology is ischemic. However, by detecting lower levels of cTn, 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 a hs-cTn level measured on presentation and 2 to 3 hours later (at 0 and 6 hours if using a standard cTn assay).

All laboratory tests should be interpreted in the context of the pre-test disease probability (see also Understanding Medical Tests and Test Results Likelihood ratios (LRs) Test results may help make a diagnosis in symptomatic patients (diagnostic testing) or identify occult disease in asymptomatic patients (screening). If the tests were appropriately ordered on... read more ). This is especially relevant for the hs-cTn assay, given the very high sensitivity of this test, but applies to all assays of cTn.

The patient's pre-test probability of disease is estimated clinically based on:

A high pre-test probability plus an elevated cTn level is highly suggestive of myocardial infarction, whereas a low pre-test probability plus a normal cTn is unlikely to represent myocardial infarction. Diagnosis is more challenging when test results are discordant with pre-test probability, in which case serial cTn levels often help. A patient with low pre-test probability and an initially slightly elevated 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 cTn level that rises > 50% when the cTc is re-measured, myocardial infarction is likely; continued normal levels (often including at 6 hours and beyond when suspicion is high) suggest the need to pursue an alternate diagnosis.

Coronary angiography Angiography Angiography is sometimes called conventional angiography to distinguish it from CT angiography (CTA) and magnetic resonance angiography (MRA). Angiography provides detailed images of blood vessels... read more 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 myocardial infarction (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 hours).

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 hours 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 patients with STEMI who have inducible ischemia on stress imaging or an ejection fraction < 40%.

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], and pain management with nitrates) can reduce risk of mortality and complications. Early diagnostic data and response to treatment can help determine the need for and timing of revascularization Revascularization for Acute Coronary Syndromes Revascularization is the restoration of blood supply to ischemic myocardium in an effort to limit ongoing damage, reduce ventricular irritability, and improve short-term and long-term outcomes... read more .

On arrival to the emergency department, 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 hours 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 Antiplatelet Drugs Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more , anticoagulants Anticoagulant Drugs Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more , 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 Drugs for Acute Coronary Syndromes Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more . Other drugs, such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins, should also be given (see table Drugs for Coronary Artery Disease Drugs for Coronary Artery Disease* ).

Patients with acute myocardial infarction should be given the following (unless contraindicated):

All patients are given aspirin 160 to 325 mg (not enteric-coated), if not contraindicated, at presentation and 81 mg once a 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 orally once), prasugrel (60 mg orally once), or ticagrelor (180 mg orally once) improves outcomes, particularly when administered 24 hours 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 unless contraindicated (eg, by active bleeding). Unfractionated heparin is more complicated to use because it requires frequent (every 6 hours) dosing adjustments to achieve target activated partial thromboplastin time (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 Heparin-induced thrombocytopenia Platelet destruction can develop because of immunologic causes (viral infection, drugs, connective tissue or lymphoproliferative disorders, blood transfusions) or nonimmunologic causes (sepsis... read more . Bivalirudin is recommended for patients with a known or suspected history of heparin-induced thrombocytopenia Anticoagulants are continued for:

Consider a glycoprotein IIb/IIIa inhibitor during PCI for high-risk lesions (high thrombus burden, no reflow). Abciximab, tirofiban, and eptifibatide appear to have equivalent efficacy, and the choice of drug should depend on other factors (eg, cost, availability, familiarity). This agent is continued for 6 to 24 hours.

Chest pain can be treated with nitroglycerin or sometimes morphine. Nitroglycerin is preferable to morphine, which should be used judiciously (eg, if a patient has a contraindication to nitroglycerin or is in pain despite nitroglycerin therapy). Nitroglycerin Nitrates Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more is initially given sublingually, followed by continuous IV drip if needed. Morphine 2 to 4 mg IV, repeated every 15 minutes as needed, is highly effective but can depress respiration, can reduce myocardial contractility, and is a potent venous vasodilator. Evidence also suggests that morphine use interferes with some P2Y12 receptor inhibitors. A large retrospective trial showed that morphine may increase mortality in patients with acute myocardial infarction (1, 2 Treatment references Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more ). Hypotension and bradycardia secondary to morphine can usually be overcome by prompt elevation of the lower extremities.

Standard therapy for all patients with unstable angina includes beta-blockers, ACE inhibitors, and statins. Beta-blockers Beta-Blockers Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more 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 Other Drugs Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more 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 Other Drugs Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more may be substituted. Statins Other Drugs Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more are also standard therapy regardless of lipid levels 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 minutes) by an experienced operator (3 Treatment references Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more ). If there is likely to be a significant delay in availability of PCI, thrombolysis should be done for STEMI patients meeting criteria (see Infarct extent Infarct extent Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and/or diaphoresis... read more ). 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 minutes. Greatest benefit occurs within 3 hours, but the drugs may be effective up to 12 hours. Characteristics and selection of fibrinolytic drugs Fibrinolytics Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications... read more 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 coronary artery bypass grafting (CABG).

For uncomplicated NSTEMI patients, immediate reperfusion is not as urgent because a completely occluded infarct-related artery at presentation is uncommon. Such patients typically undergo angiography within the first 24 to 48 hours of hospitalization to identify coronary lesions requiring PCI or CABG.

Fibrinolytics are not indicated for any NSTEMI patients. Risk outweighs potential benefit.

Choice of reperfusion strategy is further discussed in Revascularization for Acute Coronary Syndromes Revascularization for Acute Coronary Syndromes Revascularization is the restoration of blood supply to ischemic myocardium in an effort to limit ongoing damage, reduce ventricular irritability, and improve short-term and long-term outcomes... read more .

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 hours, 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 Myocardial Infarction Functional Evaluation After Myocardial Infarction ).

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.