Myocardial infarction (MI) is a clinical syndrome characterized by symptoms of myocardial ischemia, persistent electrocardiographic (ECG) changes, and release of biomarkers of myocardial necrosis resulting from an insufficient supply of oxygenated blood to an area of the heart. MI may be classified as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) depending on the ECG findings on MI presentation. Acute coronary syndrome (ACS) refers to acute myocardial ischemia without myocardial necrosis (unstable angina) and myocardial necrosis and infarction (NSTEMI or STEMI). According to the European Society of Cardiology/American College of Cardiology guidelines, the following criteria for acute evolving or recent MI (NSTEMI and STEMI) satisfies the diagnosis:

• Detection of the rise and/or fall of cardiac biomarker values (preferably cardiac troponin [cTn]) with at least one value above the 99th percentile upper reference limit and with at least one of the following:
  1. Symptoms of ischemia
  2. Development of pathologic Q waves in the ECG
  3. Imaging evidence of new loss of viable myocardium or a new regional wall motion abnormality
  4. Identification of an intracoronary thrombus by angiography or autopsy pathologic findings of acute MI
  5. Electrocardiogram criteria:
     1. STEMI:
        1. New, or presumed new, significant ST-T changes or new left bundle branch block (LBBB) in appropriate clinical setting
        2. New ST elevation at the J-point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2 to V3 and/or of ≥1 mm (0.1 mV) in another contiguous chest leads or the upper limb leads
     2. NSTEMI:
        1. New ST-segment depression ≥0.5 mV (0.5 mm) and T-wave abnormalities

New generation troponin assays are extremely sensitive to small changes in serum troponin levels at the cost of diagnostic specificity for MI related to plaque rupture or erosion.

Universal classification of acute MI:

• Type 1: Spontaneous MI related to ischemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring, or dissection.
• Type 2: MI secondary to ischemia, other than coronary artery disease, due to either increased oxygen demand or decreased supply (e.g., coronary endothelial dysfunction, coronary artery spasm, coronary embolism, anemia, arrhythmias, respiratory failure, hypertension with/without left ventricular hypertrophy [LVH], or hypotension). Also, in critically ill patients or in patients undergoing major noncardiac surgery, elevated values of cardiac biomarkers may appear due to the direct toxic effects of endogenous or exogenous high circulating catecholamine levels.
• Type 3: Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia, accompanied by presumed new ST elevation, new left bundle branch block, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, or death occurring before blood samples could be obtained or at a time before the appearance of cardiac biomarkers in the blood.
• Type 4a: MI associated with percutaneous coronary intervention. Elevation of cTn >5× percentile of upper reference limit (URL) in patients with normal baseline value, or a rise of cTn >20% if the baseline values are stable and are stable or falling. In addition to either symptoms of ischemia, new ischemic ECG changes or new LBBB, or angiographic loss of a patent coronary artery, persistent slow or no-flow, or embolization, or imaging of new wall motion abnormality.
• Type 4b: MI associated with stent thrombosis as documented by angiography or at autopsy in the setting of myocardial ischemia and with a rise/fall of cardiac biomarker values.
• Type 5: MI associated with coronary artery bypass grafting. Elevation of cardiac biomarker values >10× 99% URL in patients with normal baseline cTn values, in addition to either new pathologic Q waves or new LBBB, or new native coronary artery occlusion or imaging of new abnormal wall motion abnormality.
• Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): It is defined as acute myocardial infarction in the absence of obstructive coronary artery disease. Conditions like Takotsubo cardiomyopathy, spontaneous coronary artery dissection, coronary artery spasm, microvascular dysfunction, and pulmonary embolism come under this novel category.

MI

ST-elevation MI

Heart attack

Acute myocardial infarction

AMI

Coronary thrombosis

Coronary occlusion

The clinical presentation of myocardial infarction is usually based on a history of substernal pressure-type chest pain radiated to the neck, lower jaw, left arm, or mid-back lasting 20 min or more that is not completely relieved by sublingual nitroglycerin. The pain may not be severe. Some patients may present with atypical symptoms such as nausea/vomiting, shortness of breath, fatigue, palpitations, and diaphoresis. The elderly in particular may present with dizziness or syncope. The patients who tend to present with atypical symptoms are more likely to be women, diabetic patients, or elderly patients and less frequently receive reperfusion therapy and other evidence-based therapies than patients with a typical chest pain presentation. Records show that up to 30% of patients with STEMI present with atypical symptoms.

Physical findings:

• Skin may be diaphoretic and exhibit pallor (because of decreased oxygen).
• Rales may be present at the bases of lungs (indicative of heart failure [HF]).
• Cardiac auscultation may reveal an apical systolic murmur caused by mitral regurgitation from papillary muscle dysfunction; S3 or S4 may also be present.
• Up to 10% of patients may present with acute pulmonary edema and/or cardiogenic shock.
• Physical examination may be completely normal.

• Coronary atherosclerosis and plaque rupture
• Coronary artery spasm
• Coronary embolism (caused by infective endocarditis, rheumatic heart disease, intracavitary thrombus, atrial fibrillation)
• Periarteritis and other coronary artery inflammatory diseases
• Dissection into coronary arteries (aneurysmal or iatrogenic or spontaneous)
• Anomalous origin of coronary artery, especially interarterial (aorta and pulmonary artery) course of coronary artery
• MI with normal coronaries: More frequent in younger patients and cocaine addicts. The risk of acute MI is increased by a factor of 24 during the 60 min after the use of cocaine in persons who are otherwise at relatively low risk. Most patients with cocaine-related MI are young, nonwhite, male cigarette smokers without other risk factors for coronary heart disease and who have a history of repeated cocaine use. Blood and urine toxicology screen for cocaine is recommended in all young patients who present with acute MI
• Hypercoagulable states, increased blood viscosity (polycythemia vera and autoimmune diseases such as systemic lupus, antiphospholipid syndrome)

The various causes of myocardial ischemia are described along with the differential diagnosis of chest pain.

• Electrocardiogram (Fig. 1): A 12-lead ECG should be performed and shown to an experienced emergency physician within 10 min of emergency department (ED) arrival for all patients with chest discomfort (or anginal equivalent) or other symptoms suggestive of MI. Table 1 and Table 2 describe ECG findings in myocardial infarction. If the initial ECG is not diagnostic for MI but the patient remains symptomatic and there is a high clinical suspicion for MI, serial ECGs at 5- to 10-min intervals or continuous 12-lead ST-segment monitoring should be performed to detect the potential development of ST deviation. In patients with inferior STEMI, right-sided ECG leads should be obtained to look for ST elevation suggestive of right ventricular (RV) infarction. The joint ESC/ACCF/AHA committee for the definition of MI established the definition for the diagnosis of ST-elevation MI, which is considered to be present when there is an ST-segment elevation in two contiguous leads, ≥2 mm for men and ≥1.5 mm for women in precordial leads and/or ≥1 mm in limb leads. ST-segment elevation is measured at 0.08 sec after the J point (the junction between the end of the QRS and the beginning of the ST segment). In addition, ST depression in >2 precordial leads (V1 to V4) may indicate transmural posterior injury; multilead ST depression with coexistent ST elevation in lead aVR has been described in patients with left main or proximal left anterior descending artery involvement.
• New or presumably new LBBB at presentation occurs infrequently, may interfere with ST-elevation analysis. Thus consider MI only if clinically appropriate.
• Diagnosing new STEMI in patients with old left bundle branch block could be challenging. Sgarbossa and colleagues emphasized that concordant 1 mm ST-segment elevation in any lead with a positive QRS deflection or discordant ST-segment elevation >5 mm in any lead with negative QRS deflection suggest STEMI.
• New ST-segment depression ≥0.5 mV (0.5 mm) and T-wave abnormalities suggest NSTEMI. ECG findings alone, without laboratory results, are sufficient to diagnose STEMI; therefore treatment should not be delayed until biomarkers are available.
• Cardiac troponin levels: Cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnI) are generally indicative of myocardial injury with increases in serum levels of >99th percentile of a normal reference population. Detection of a rise and fall pattern of the measurements is essential to the diagnosis of AMI. The rise may occur relatively early after muscle damage (3 to 6 hr), peak at 12 to 16 hr, and may be present for several days after MI (up to 7 days for cTnI and more than 14 days for cTnT). Earlier peaking and rapid decline of cardiac enzymes may present in light of successful revascularization (Fig. 2). cTnT or cTnI tests can be falsely positive for myocardial infarction in patients with renal failure, heart failure, myocarditis, aortic dissection, and pulmonary embolism. Recently, highly sensitive troponin assays (hs-cTnI, hs-cTnT) have also been developed to facilitate an early diagnosis of AMI. Most patients can be diagnosed with AMI within the first 2 to 3 hr of presentation. However, an initial negative high-sensitivity troponin at the time of presentation is not sensitive enough to completely rule out AMI. MI can be excluded in most patients by 6 hr of presentation, and guidelines suggest serial samples be obtained every 3 to 6 hr after an initial sample if there is a high degree of suspicion for AMI(1&2).
• Troponin is the preferred marker for the diagnosis of myocardial necrosis. A single high-sensitivity assay for cardiac troponin (hs-cTnT) concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out an MI in patients presenting to EDs with possible emergency acute coronary syndrome.² Because troponins need 7 to 14 days to be cleared by the kidneys, they are not sensitive enough to detect a recurrent MI within days from the initial MI. CK-MB isoenzyme can be useful in such circumstances (see Fig. 2).
• CK-MB isoenzyme is also a useful marker for MI if troponin levels are not available. It is released in the circulation in amounts that correlate with the size of the infarct. An increased CK-MB value for the diagnosis of MI is defined as a measurement above the 99th percentile of the upper reference limit. CK-MB can be detected within 3 to 8 hr of the onset of chest pain, peak at 12 to 24 hr, and return to baseline levels within 24 to 48 hr.

Imaging studies such as a high-quality portable chest X-ray, transthoracic echocardiography, and a contrast chest computed tomography (CT) scan should be used to differentiate MI from aortic dissection, pulmonary embolism, and other intrathoracic causes of chest pain (i.e., pneumonia and pneumothorax) in patients for whom this distinction is initially unclear, or to assess for complications of AMI such as pulmonary edema. Transthoracic echocardiography may provide evidence of focal wall motion abnormalities and facilitate triage in patients with ECG findings that are difficult to interpret.

For STEMI patients, TIMI (Thrombolysis in Myocardial Infarction) risk index, TIMI risk score (30-day outcomes), and GRACE (Global Registry of Acute Coronary Events) risk score (6-mo outcomes) are commonly available risk assessment models. In the TIMI risk score for STEMI, the mean 30-day mortality was 6.7%. It is composed of eight baseline variables. The risk score showed a >40-fold graded increase in mortality, with scores ranging from 0 to >8 (P <0.0001); 30-day mortality was 0.1% among patients with a score of 0, 2.25 with a score of 5, and >8.8% among patients with a score of 8 or greater. The higher the score, the higher the 30-day mortality rate. The variables are divided between historic, exam, and presentation:

• Limit patient’s activity: Bed rest with bedside commode for the initial 12 to 24 hr. If the patient remains stable, gradually increase.
• Diet: Nothing by mouth until stable, then clear liquids as tolerated to advance gradually to a diet tailored to the patient’s comorbidities (i.e., diabetes, hypertension, heart failure, hyperlipidemia, renal failure, chronic obstructive pulmonary disease [COPD], etc.).
• Patient education to decrease the risk of subsequent cardiac events, counseling on smoking cessation, dietary restrictions, regular exercise, and medication compliance should be initiated when the patient is medically stable.

• Fig. 3 shows a treatment algorithm for STEMI. Assessment and treatment algorithm for non-ST-segment MI is described in Fig. 4. Rationale of the treatment of a patient with STEMI is based on “time is muscle.” Therefore all communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of EMS and hospital-based activities. A 12-lead ECG must be done by EMS personnel at the site of first medical contact (FMC).
• Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within 12 hr. Indications for primary angioplasty and comparison with fibrinolytic therapy are described in Table 3. Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators with an ideal FMC-to-device time system goal of 90 min or less.
• In the absence of contraindications, fibrinolytic therapy (Table 4) should be administered to patients with STEMI at non-PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 min because of unavoidable delays. Door-in door-out time (DIDO) for fibrinolytic therapy should be less than 30 min. If more than 30 min delay, transfer the patient to a PCI-capable hospital.
• Among STEMI patients who were treated with fibrinolytics, patients with >50% ST-segment resolution on EKG were at much lower risk for cardiac-related mortality compared with those with <50% resolution at 30 days.
• PCI is superior to thrombolytic therapy and is the standard of care. It is effective and generally results in more favorable outcomes than thrombolytic therapy.
• Primary PCI should be performed in patients with STEMI and persistent ischemic symptoms and who have contraindications to fibrinolytic therapy, irrespective of the time delay from FMC, or in patients with cardiogenic shock or acute severe HF irrespective of time delay from myocardial infarction (MI) onset, first medical contact to balloon time is <90 min or door to balloon/door to needle time is <1 hr, symptoms onset was >3 hr ago and when diagnosis of STEMI in doubt. Coronary stents (drug-eluting or bare-metal) are useful in patients with STEMI (3,4,5 &6).
• The question of culprit vessel vs. complete revascularization during PCI has been brought up since the stent technology was applied to the management of STEMI. The most recent clinical trials (CuLPRIT, PRAMI, and DANAMI3-PRIMULTI [FFR-driven revascularization]) appear to favor complete revascularization in the setting of STEMI. However, CULPRIT-SHOCK trial showed culprit vessel only PCI associated with 9.5% absolute reduction in the rate of death or renal replacement therapy at 30 days compared to multivessel PCI in acute MI patients with cardiogenic shock. One-yr outcomes did not show significant difference in mortality between two groups. Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) Registry data showed better outcomes with multivessel PCI in cardiogenic shock patients compared to culprit vessel-only PCI. Thus multivessel PCI should be reserved for few selective patients.
• For patients presenting to a non-PCI-capable hospital, rapid assessment should be done of (1) the time from onset of symptoms, (2) the risk of complications related to STEMI, (3) the risk of bleeding with fibrinolysis, (4) the presence of shock or severe HF, and (5) the time required for transfer to a PCI-capable hospital and a decision about administration of fibrinolytic therapy reached. Because the effectiveness of thrombolytics is time dependent, these agents should ideally be administered either in the field or within 30 min of the patient’s arrival to the emergency department (door-to-needle time).
• Fibrinolytic therapy: If tissue plasminogen activator (t PA) or reteplase is used, anticoagulants, such as heparin, are given to increase the likelihood of patency in the infarct-related artery for 48 hr and preferably for the duration of the index hospitalization, up to 8 days. In patients receiving fibrinolysis for STEMI, treatment with enoxaparin is superior to treatment with unfractionated heparin for 48 hr but is associated with an increase in major bleeding episodes. In patients receiving streptokinase or APSAC, heparin after thrombolysis is not indicated because it does not offer any additional benefit and can result in increased bleeding complications. Tenecteplase and reteplase are comparable with accelerated infusion recombinant t-PA in terms of efficacy and safety but are more convenient because they are administered by bolus injection. Lanoplase and heparin bolus plus infusion are as effective as tPA with regard to mortality rate, but the rate of intracranial hemorrhage is significantly higher.
• Absolute contraindications to thrombolytic therapy (Table 5) include history of intracranial hemorrhage, known intracranial malignant neoplasm or arteriovenous malformation, ischemic stroke within 3 mo (except acute ischemic stroke within 4.5 hr), suspected aortic dissection, active bleeding or bleeding diathesis (except menses), significant closed head or facial trauma within 3 mo, intracranial or intraspinal surgery within 2 mo, or severe uncontrolled hypertension (unresponsive to therapy). For streptokinase, this applies to prior treatment within 6 mo.
• Relative contraindications: History of chronic severe, poorly controlled hypertension, SBP >180 mm Hg, diastolic blood pressure (DBP) >110 mm Hg, history of prior ischemic stroke more than 3 mo, dementia, known intracranial pathology, traumatic or prolonged cardiopulmonary resuscitation (CPR) (>10 min), major surgery <3 wk, recent internal bleeding within 2 to 4 wk, noncompressible vascular punctures, pregnancy, active peptic ulcer, oral anticoagulant therapy. After the administration of thrombolytics, immediate transfer to a PCI-capable facility is advisable without waiting for lytic results.
• Transfer to a PCI-capable hospital: Immediate transfer for STEMI patients who develop cardiogenic shock or acute severe HF, irrespective of the time delay from MI onset. Urgent transfer if the patient demonstrates evidence of failed reperfusion or reocclusion after fibrinolytic therapy.
• Coronary angiography should not be performed within the first 2 to 3 hr after administration of fibrinolytic therapy.
• Coronary artery bypass graft (CABG): Urgent CABG is indicated in patients with STEMI and coronary anatomy not amenable to PCI who have ongoing or recurrent ischemia, cardiogenic shock, severe HF, or other high-risk features. CABG is recommended in patients with STEMI at time of operative repair of mechanical defects. Box 1 summarizes CABG in patients with MI.
• Therapeutic hypothermia should be started as soon as possible in comatose patients with STEMI and out-of-hospital cardiac arrest caused by ventricular fibrillation (VF) or pulseless ventricular tachycardia, including patients who undergo primary PCI.
• Immediate angiography and PCI when indicated should be performed in resuscitated out-of-hospital patients.
• The use of mechanical circulatory support is reasonable in patients with STEMI who are hemodynamically unstable and require urgent CABG.
• For NSTEMI patients, immediate invasive strategy (within 2 hr) recommended in patients with refractory angina, signs or symptoms of congestive heart failure or new or worsening ischemic mitral regurgitation, hemodynamic instability, recurrent angina or ischemia at rest or with low level activities despite intensive medical therapy and sustained ventricular tachycardia or ventricular fibrillation.
• Early invasive strategy (<24 hr) for NSTEMI patients recommended if GRACE risk for more than 140, dynamic ST changes on EKG and temporal change in troponin levels.
• NSTEMI patient with low-risk TIMI score (0 or 1) and/or low GRACE score (<109) and/or troponin-negative female patients can benefit from ischemia-guided strategy. Fibrinolytic therapy is contraindicated in NSTEMI patients.
• Medical therapy should be initiated immediately in the emergency department for all MI patients. This includes:
  1. Routine measures
     1. Oxygen: Supplemental oxygen should be administered to patients with arterial oxygen desaturation (SaO₂ less than 90%). No benefit has been demonstrated to supplemental oxygen in patients with normal SaO_2.
     2. Nitroglycerin: Increase oxygen supply by reducing coronary vasospasm and decrease oxygen consumption by reducing ventricular preload. Patients with ongoing ischemic discomfort should receive sublingual nitroglycerin every 5 min for a total of three doses, after which an assessment should be made about the need for intravenous nitroglycerin. Intravenous nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion. Nitrates should not be administered to patients whose systolic blood pressure is <90 mm Hg or ≥30 mm Hg below baseline or severe bradycardia (<50 beats/min), tachycardia (>100 beats/min), or suspected RV infarction. Nitrates should not be administered to patients who have received a phosphodiesterase inhibitor for erectile dysfunction within the last 24 hr (48 hr for tadalafil).
     3. Adequate analgesia: Morphine sulfate 2 to 4 mg intravenous (IV) initially with increments of 2 to 8 mg IV at 5- to 10-min intervals can be given for severe pain unrelieved by nitroglycerin. Morphine can reduce the catecholamine surge caused by anxiety and pain, particularly in patients with anterior myocardial infarctions, which in turn can reduce heart rate and pulmonary capillary wedge pressure (PCWP), the increased cardiac workload and oxygen demand, leading to decreased ischemia and pulmonary congestion. Hypotension from morphine can be treated with careful IV hydration with saline solution. If sinus bradycardia accompanies hypotension, use atropine (0.5 to 1.0 mg IV q5min prn to a total dose of 2.5 mg). Respiratory depression caused by morphine can be reversed with naloxone 0.8 mg. Morphine sulfate and nitroglycerine should be avoided in patients with RV involvement who usually present with bradycardia and hypotension. Pain management in these cases should be provided preferentially with meperidine 25 to 50 mg intravenously q4h, in combination with Phenergan 12.5 mg to prevent nausea and/or vomiting. Blood pressure support with normal saline solution is of critical importance to maintain adequate hemodynamics until optimal revascularization is accomplished.
     4. Aspirin 162 to 325 mg PO should be crushed and chewed to enhance drug absorption and delivery. It should be given as soon as possible and continued indefinitely at 81 mg daily. Depending on the clinical and ECG findings, if the patient is suspected to have a coronary anatomy that needs CABG rather than PCI, aspirin should be continued. P2Y12 receptor antagonists should be avoided (except cangrelor) because they increase the perioperative bleeding risk; on-pump surgery should be deferred for at least 24 hr after clopidogrel and ticagrelor. Off-pump surgery might be considered within 24 hr of clopidogrel or ticagrelor if the benefits of revascularization outweigh the risk of bleeding. However, if the coronary artery disease is likely to benefit from PCI alone, then a loading dose of clopidogrel 600 or 300 mg or ticagrelor 180 mg PO or prasugrel 60 mg should be given as early as possible and no later than 1 hr after PCI. P2Y12 receptor antagonist should be continued for at least 1 yr after acute coronary syndrome or after primary PCI. Prasugrel showed significant net clinical benefit (MACE vs. bleeding complications) only in patients with MI who underwent revascularization. It shouldn’t be given for non-revascularized patients. Ticagrelor or clopidogrel can be given in patients with MI with or without catheter-based revascularization. Cangrelor is the newest direct-acting P2Y12 platelet receptor inhibitor. It has a similar chemical structure to ATP, with a half-life of 3 to 6 min. It is given IV as a bolus plus 120 min of infusion at the time of primary PCI in patients who are naïve to P2Y12 receptor antagonists. It was approved by the FDA in 2015 after the CHAMPION PHOENIX trial. Clopidogrel and prasugrel should be started after its infusion is finished. The ticagrelor loading dose can be given during the infusion. Considering rapid onset action and clearance, cangrelor can be started in the emergency room at the time of high-risk acute myocardial infarction diagnosis irrespective surgical or catheter-based revascularization.
  2. In patients receiving fibrinolytics only or balloon angioplasty without stent, P2Y12 antagonists can be given for as little as 14 days. Clopidogrel is recommended for postfibrinolytic patients.
  3. Unfractionated heparin (UFH) is recommended in all patients with NSTEMI and STEMI (fibrinolysis or invasive revascularization). UFH infusion should not exceed more than 48 hr after PCI or fibrinolysis in the absence of an ongoing indication due to risk of heparin-induced thrombocytopenia. NSTEMI patients who underwent ischemia-guided therapy, low-molecular- weight heparin (LMWH) showed better MACE outcomes compared with UFH. The benefit was not significant in revascularized patients. Bivalirudin was associated with lower MACE and bleeding events in STEMI patients compared with UFH. However, it increased the risk of stent thrombosis. In NSTEMI patients who are undergoing PCI, LMWH, bivalirudin, and UFH are acceptable.
  4. Beta-adrenergic blocking agents should generally be given to all patients who do not exhibit evidence of shock. Table 6 summarizes recommendations for β-blocker therapy for STEMI. β-blockers are useful to reduce myocardial oxygen consumption and prevent tachyarrhythmias. Early IV beta blockage (in the initial 24 hr) followed by institution of an oral maintenance regimen is also effective in reducing recurrent infarction and ischemia. Oral β-blockers should be initiated in the first 24 hr in patients with MI who do not have any of the following: Signs of HF, evidence of a low-output state, sinus tachycardia, increased risk for cardiogenic shock, or other contraindications for its use (bradycardia, PR interval more than 0.24 sec, second- or third-degree heart block, active asthma, or reactive airways disease).
  5. They should be continued during and after hospitalization for all patients with MI and with no contraindications to their use for at least 2 yr. Patients with initial contraindications to the use of β-blockers in the first 24 hr after MI should be reevaluated to determine their subsequent eligibility. It is reasonable to administer intravenous β-blockers at the time of presentation to patients with MI and no contraindications to their use who are hypertensive or have ongoing ischemia.
  6. In patients with acute MI, treatment with drug-eluting stents is associated with decreased mortality rates and a reduction in the need for repeated revascularization procedures compared with treatment including bare-metal stents.
  7. Gp IIb/IIIa inhibitors in the era of DAPT therapy and primary PCI have failed to show benefit with “upstream” treatment. Abciximab might be useful in the presence of large thrombus burden during primary PCI. For patients receiving bivalirudin as the primary anticoagulant, routine adjunctive use of GP IIb/IIIa inhibitors is not recommended but may be considered as adjunctive or “bail-out” therapy in selected cases. In patients with acute coronary syndrome with high-risk features and not adequately pretreated with P2Y12 inhibitors, it is useful to administer GP IIb/IIIa inhibitors at the time of PCI.

Figure 3 Reperfusion therapy for patients with STEMI.

∗Patients with cardiogenic shock or severe heart failure initially seen at a non-PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset. +Angiography and revascularization should not be performed within the first 2 to 3 hr after administration of fibrinolytic therapy. ACS, Acute coronary syndrome; CABG, coronary artery bypass graft; Cath, catheterization; DIDO, door-in to door-out; EKG, electrocardiogram; FMC, first medical contact; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

Modified from O’Gara PT et al: 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, JACC 61(4):e78-e140, 2013.

• Discharge medications in all patients with MI (unless contraindicated) should include antiischemic medications (e.g., nitroglycerin, β-blocker), lipid-lowering agents, and antiplatelet therapy (aspirin and/or P2Y12 antagonists).
• Aspirin, 81 mg PO daily, but should be continued indefinitely unless not tolerated (e.g., GI bleed). In MI patients, clopidogrel 75 mg PO daily; ticagrelor, 90 mg bid, or prasugrel, 10 mg PO daily, can be combined with aspirin and should be continued without interruption for a minimum of 12 mo after drug-eluting stent placement; however, aspirin should be continued indefinitely. In cases of high bleeding risk or significant overt bleeding, consider discontinuation of P2Y12 inhibitor after 6 mo (Fig. 5). Combining P2Y12 antagonists with aspirin reduces risk for repeat myocardial infarction and stent thrombosis. If there is an elective surgical intervention pending, it is recommended to defer the surgery until completion of the full course of the P2Y12 antagonist treatment. Duration dual antiplatelet therapy in high-bleeding-risk (HBR) patients is debatable. Many randomized controlled trials support single antiplatelet therapy 1 or 3 mo after PCI in HBR acute coronary syndrome populations.
• Angiotensin-converting enzyme inhibitors (ACEIs) should be started within the first 24 hr of MI to all patients having MI with anterior infarction, pulmonary congestion, or LV EF <40%, in the absence of hypotension. They reduce LV dysfunction and dilation and slow the progression to HF during and after acute MI. Angiotensin receptor blockers (ARBs) should be given to patients who have indication but are intolerant of ACEIs. IV formulations of ACEIs should not be given within the first 24 hr of STEMI due to risk of hypotension. ARBs offer no advantage over ACEIs and should be considered only in patients who are intolerant to ACEIs.
  1. ACEIs may be stopped in patients without complications and no evidence of LV dysfunction after 6 to 8 wk.
  2. ACEIs should be continued indefinitely in patients with impaired LV function (EF <40%) or clinical HF.
• Long-term aldosterone antagonist therapy should be prescribed for post-MI patients without significant renal dysfunction (creatinine ≤2.5 mg/dl in men and ≤2.0 mg/dl in women) or hyperkalemia who are already taking an ACEI, a β-blocker, and have LV EF <40% with symptomatic HF or diabetes.
• In late 2018, American College of Cardiology (ACC) recommended LDL goal of <70 mg/dl for secondary prevention of atherosclerotic cardiovascular disease. Goal should further be reduced to <55mg/dl in patients with existing atherosclerotic vascular disease and familial hypercholesterolemia. High-intensity statins (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg) should be started as early as possible in all patients with MI regardless of lipid panel, not only for their lipid-lowering effects, but also their antiinflammatory properties (JUPITER trial), which can stabilize the ruptured plaque. Atorvastatin 80 mg can be used (PROVE IT-TIMI 22 and MIRACL trials). IMPROVE-IT trial showed adding ezetimibe to statin treatment could decrease recurrent MI and ischemic stroke in MI patients. FDA also approved two PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors (alirocumab and evolocumab) for heterozygous familial hypercholesterolemia patients who are receiving maximally tolerated statins or patients with clinical atherosclerotic cardiovascular disease who require lowering LDL levels. Newer 2018 lipid guidelines suggested starting PCSK9 inhibitor in very high-risk atherosclerotic cardiovascular disease patients who did not meet the LDL goal on high intensity statin and ezetimibe. One should always consider adding ezetimibe to high intensity statin prior to initiation of PCSK9 inhibitor due to cost issues. A fasting lipid panel should be checked during the first 24 hr of hospital course, and the intensive therapy can be stepped down if appropriate. Inclisiran, evinacumab and bempedoic acid are reasonable non-statin therapy alternatives in patients who are unable to tolerate statin and reach target LDL levels.
• In diabetic patients, HbA1c goal should be aimed at below or around 7.0% to reduce micro- and macrovascular complications. Oral hypoglycemic agents GLP1 (glucagon-like peptide) agonist (liraglutide) and SGLT2 (sodium-glucose cotransporter) inhibitor (empagliflozin) showed significant mortality benefit in type 2 diabetic patients with history of CAD.
• ACC/AHA 2017 hypertension guidelines recommend initiation of blood pressure (BP)-lowering medications in patients with clinical CVD and an average SBP ≥130 mm Hg or a DBP ≥80 mm Hg for goal BP of <130/80.

• Cardiogenic shock: Emergent revascularization with either PCI or CABG is the recommended treatment.
• Sustained ventricular tachycardia: Implantable cardioverter-defibrillator therapy (ICD) is indicated before discharge in patients who develop sustained ventricular tachycardia/ventricular fibrillation more than 48 hr after STEMI, provided the arrhythmia is not due to transient or reversible ischemia, reinfarction, or metabolic abnormalities.
• Pacing in MI: Temporary pacing is indicated for symptomatic bradyarrhythmias unresponsive to medical treatment and after revascularization. AV block and bradyarrhythmias in the setting of inferior wall MI are usually transient, will not require long-term pacing, and usually resolve within 2 to 4 wk of the event. On the contrary, AV block and bradyarrhythmias or new LBBB in the presence of an anterior wall MI is usually a sign of severe disruption of the bundle of His and often requires a permanent pacemaker.
• Pericarditis after MI: Post-MI pericarditis can occur early after MI. Dressler syndrome is an autoimmune inflammatory reaction to myocardial antigen after myocardial infarction. Symptoms of pericarditis usually occur 2 to 3 wk after myocardial infarction. Aspirin is recommended for treatment of pericarditis after MI. Glucocorticoids and nonsteroidal antiinflammatory drugs are potentially harmful for treatment of pericarditis after STEMI.
• Severe mitral regurgitation from papillary muscle rupture (1%), interventricular septum rupture (0.2%), and free wall rupture (1% to 3%) are the three major mechanical complications that can occur after acute myocardial infarction. Echocardiogram is helpful in diagnosing papillary muscle rupture, ventricular septal rupture, and free wall rupture. Right heart catheterization is needed to show “step-up” in oxygen saturation at the level of right ventricle. Emergent surgical repair is the treatment of choice for ventricular free wall rupture, intraventricular septum rupture, and papillary muscle rupture.

• Noninvasive testing for ischemia should be performed before discharge to assess the presence and extent of inducible ischemia in patients with STEMI who have not had coronary angiography and do not have high-risk clinical features for which coronary angiography would be warranted. It might be considered before discharge to evaluate the functional significance of a noninfarct artery stenosis previously identified at angiography and/or before discharge to guide the postdischarge exercise prescription.
• Assessment of LV function: LV ejection fraction should be measured in all patients with STEMI. Echocardiography to rule out presence of mural thrombi in patients suspected of having an extensive infarction (more common with anterior wall MI); contrast echocardiography is added if mural thrombus is suspected.
  1. Assessment of risk for sudden cardiac death: Patients with an initially reduced LV ejection fraction, <40%, who are possible candidates for implantable cardioverter-defibrillator therapy should undergo reevaluation of LV ejection fraction at 90 days (or 42 days if no revascularization was performed). ICD is recommended when LVEF remains <35% in the presence of NYHA class II or III heart failure, or in patients with LVEF <30% regardless of symptoms, if the life expectancy is >1 yr.
• Cardiac rehabilitation/secondary prevention programs are recommended for patients with STEMI.

The prognosis after MI depends on multiple factors:

• New bundle branch block, Mobitz II second-degree block, and third-degree heart block adversely affect outcome.
• Size of infarct: The larger it is, the higher the post-MI mortality rate. Significant myocardial stunning with subsequent improvement of ventricular function occurs in most patients after anterior MI. A lower level of creatine kinase, an estimate of the extent of necrosis, is independently predictive of recovery of function.
• Site of infarct: Inferior wall MI carries a better prognosis than anterior wall MI; however, patients with inferior wall MI and right ventricular involvement have a high risk for arrhythmic complications and cardiogenic shock.
• Ejection fraction after MI: The lower the LV ejection fraction, the higher the mortality rate after MI. The risk of death is higher in the first 30 days after MI among patients with LV dysfunction, HF, or both.
• Presence of post-MI angina indicates a high mortality rate.
• Performance on low-level exercise test: The presence of ST-segment changes during the test is a predictor of high mortality rate during the first year.
• Presence of pericarditis during the acute phase of MI increases mortality rate at 1 yr.
• The Killip classification is an independent predictor of all-cause 30-day mortality:
  1. Killip class I include individuals with no clinical signs of HF. Mortality rate is 6%.
  2. Killip class II includes individuals with rales or crackles in the lungs, S3 gallop, and elevated jugular venous pressure. Mortality rate is 17%.
  3. Killip class III describes individuals with frank acute pulmonary edema. Mortality rate is 38%.
  4. Killip class IV describes individuals in cardiogenic shock or hypotension (measured as systolic blood pressure <90 mm Hg) and evidence of peripheral vasoconstriction (oliguria, cyanosis, or sweating). Mortality rate is 67%.
• Self-reported moderate alcohol consumption in the year before acute MI is associated with reduced 1-yr mortality rate.
• Discharge medication in patients with MI should include lipid-lowering agents. Statins may also lower vascular inflammation and damage by mechanisms other than reduction of low-density lipoprotein cholesterol. Early initiation of statin treatment in patients with acute MI is associated with reduced 1-yr mortality rate.
• Additional poor prognostic factors include cigarette smoking, history of hypertension or prior MI, presence of ST-segment depression in acute MI, older age, diabetes mellitus, and female sex (especially women >50 yr). Lammintausta and Fonarow reported that single men and women who live alone have a 60% to 70% greater risk of a heart attack. Furthermore, the study showed >160% increase in the risk of sudden death in these groups when compared to people who are married or live with family.
• Renal disease, even mild, as assessed by the estimated glomerular filtration rate, is a major risk factor for cardiovascular complications after MI.
• Although black patients with MI have worse outcomes than their white counterparts, these differences did not persist after adjustment for patient factors and site of care.

• Approximately 1.5 million patients undergo PCI in the U.S. each year. Depending on local practices and the diagnostic criteria used, 5% to 30% of these patients have evidence of a periprocedural MI.
• The 12-lead ECG has low sensitivity for the detection of MI if the culprit lesion is in the left circumflex artery (LCX). If the initial 12-lead ECG is not diagnostic and high clinical suspicion for acute coronary syndrome exists, it is reasonable to obtain additional posterior chest leads (V7 to V9) to detect LCX occlusion.
• Triad of hypotension, elevated jugular venous pressure, and clear lungs are suggestive of RV infarction in patients with inferior AMI. Administration of nitroglycerin is contraindicated due to hypotension. IV fluids, inotropic support, and early reperfusion are the mainstays of treatment.

Heart Attack (Patient Information)

Acute Coronary Syndrome (Related Key Topic)

Angina Pectoris (Related Key Topic)

Coronary Artery Disease (Related Key Topic)