Myocardial infarction

Myocardial infarction (MI) refers to ischemic necrosis of myocardial tissue. The most common underlying cause is coronary artery disease. Type 1 myocardial infarction occurs when an unstable plaque ruptures, leading to occlusion of a coronary artery. Type 2 myocardial infarction occurs when there is a mismatch between oxygen supply and demand (due to, e.g., systemic hypotension, vasospasm). MI manifests clinically with acute coronary syndrome (ACS), a potentially lethal condition. Diagnosis is based on typical clinical features, ECG findings, and elevation of cardiac biomarkers. Definitive diagnosis requires cardiac catheterization, which serves both diagnostic and therapeutic purposes. All patients suspected of having ACS should be considered for emergency revascularization; additional aspects of treatment include anticoagulation, antiplatelet therapy, statin therapy, and other adjunctive measures. Prevention of MI recurrence and complications consists of dual antiplatelet therapy, the initiation of beta blocker and/or ACE inhibitors, statin therapy, and addressing any modifiable risk factors.

The acute management of ACS, including diagnosis and treatment, is described in “Acute coronary syndrome.”

Myocardial infarction (MI) ^[1]

Defined as acute myocardial injury with clinical and diagnostic evidence of acute ischemia. MI is classified into 5 subtypes.

• Type 1 myocardial infarction: MI caused by atherosclerotic plaque disruption or acute coronary thrombosis
  • Most common form
  • Caused by acute thrombosis due to erosion, ulceration, fissuring, dissection, or rupture of an atherosclerotic plaque
  • ↓ Myocardial blood flow → sudden death of myocardial cells
  • Usually manifests as STEMI
• Type 2 myocardial infarction: MI secondary to an oxygen supply/demand mismatch ^[2]
  • Less common form (14%)
  • Occurs predominantly in women and in individuals with comorbidities (e.g., diabetes, previous NSTEMI)
  • Not due to plaque rupture; caused by a condition other than coronary artery disease
  • Ischemia is caused by increased oxygen demand (e.g., anemia) or decreased coronary blood supply (e.g., coronary artery spasm) ^[3][4]
• Type 3 myocardial infarction: MI resulting in death when biomarker values are unavailable
• Type 4 myocardial infarction: MI related to percutaneous coronary intervention
  • Type 4a: MI ≤ 48 hours after PCI
  • Type 4b: MI related to stent thrombosis
  • Type 4c: MI associated with restenosis after PCI
• Type 5 myocardial infarction: MI related to coronary artery bypass grafting

Acute coronary syndrome

• Suspicion or confirmed presence of acute myocardial ischemia and/or myocardial infarction
• Further classified as unstable angina, NSTEMI, and STEMI
• See “Acute coronary syndrome.”

Myocardial injury

• Cardiac troponin (cTn) level elevated above the 99^thpercentile of the upper reference limit (URL) ^[1]
• Acute myocardial injury: rise and/or fall of cTn levels in sequential measurements
• Damage may be ischemic or nonischemic.

• Incidence: ∼ 1 million cases of myocardial infarction per year in the USA ^[5]
• Sex: ♂ > ♀

Epidemiological data refers to the US, unless otherwise specified.

Any condition that causes occlusion of the coronary arteries, reduces myocardial oxygen supply, or increases oxygen demand can potentially lead to myocardial ischemia and infarction.

• Coronary artery disease: most common cause (see “Risk factors for atherosclerosis”)
• Coronary artery vasospasm (e.g., Prinzmetal angina, cocaine use)
• Coronary artery dissection
• Coronary artery embolism (e.g., due to prosthetic heart valve, atrial fibrillation)
• Takotsubo cardiomyopathy
• Myocarditis
• Thrombophilia (e.g., polycythemia vera)
• Vasculitis (e.g., polyarteritis nodosa, Kawasaki syndrome)
• Myocardial oxygen supply-demand mismatch, e.g., due to the following:
  • Hypotension
  • Severe anemia
  • Hypertrophic cardiomyopathy
  • Severe aortic stenosis

Coronary artery occlusion ^[1][6][7]

• Partial coronary artery occlusion
  • Decreased myocardial blood flow → supply-demand mismatch → myocardial ischemia
  • Usually affects the inner layer of the myocardium (subendocardial infarction)
  • Typically manifests clinically as unstable angina and/or NSTEMI (see “Acute coronary syndrome”)
• Complete coronary artery occlusion
  • Impaired myocardial blood flow → sudden death of myocardial cells (if no reperfusion occurs)
  • Usually affects the full thickness of the myocardium (transmural infarction)
  • Typically manifests clinically as STEMI

Atherosclerotic plaque disruption (type 1 MI) ^[1][6][7]

• For plaque formation, see “Coronary artery disease” and “Atherosclerosis.”
• Stable atherosclerotic plaque: manifests as stable angina (symptomatic during exertion)
• Unstable plaques are lipid-rich and covered by thin fibrous caps : high risk of rupture and acute coronary syndrome
• Inflammatory cells in the plaque (e.g., macrophages) secrete matrix metalloproteinases → breakdown of extracellular matrix → weakening of the fibrous cap → minor stress → rupture of the fibrous cap → exposure of highly thrombogenic lipid core → thrombus formation → coronary artery occlusion

Oxygen supply and demand mismatch (type 2 MI) ^[1][2]

• Can occur in patients with or without underlying coronary artery disease
• Decreased oxygen supply
  • Occlusion of coronary arteries (e.g., coronary dissection, vasospasm)
  • Reduced perfusion (e.g., hypotension, bradycardia, anemia)
• Increased oxygen demand (e.g., sustained tachyarrhythmia)

Nonischemic myocardial injury ^[1][2]

• Necrosis of myocardial tissue without ischemia (e.g., in sepsis)
• The pathophysiology of myocardial damage is not completely understood, but potential explanations include:
  • Inflammatory cytokines
  • Toxicity of high catecholamine levels

• Classic presentation ^[8][9]
  • Acute retrosternal chest pain
    • Typical: dull, squeezing pressure and/or tightness
    • Commonly radiates to left chest, arm, shoulder, neck, jaw, and/or epigastrium
    • Precipitated by exertion or stress
    • Symptom relief after administration of nitrates is not a diagnostic criterion for cardiac ischemia. ^[10]
    • The peak time of occurrence is usually in the morning.
    • See “Angina.”
  • Dyspnea (especially with exertion)
  • Pallor
  • Nausea, vomiting
  • Diaphoresis, anxiety
  • Dizziness, lightheadedness, syncope

• Other findings
  • Tachycardia, arrhythmias
  • Symptoms of CHF (e.g., orthopnea, pulmonary edema) or cardiogenic shock (e.g., hypotension, tachycardia, cold extremities)
  • New heart murmur on auscultation (e.g., new S₄)
• Atypical presentations: more likely in elderly, diabetic individuals, and women ; ^[10][11]
  • Stabbing, sharp chest pain
  • No or minimal chest pain
    • ”Silent MI” without chest pain is more common in patients with diabetes, as a result of polyneuropathy.
  • Autonomic symptoms (e.g., nausea, diaphoresis)
• More common in inferior wall infarction
  • Epigastric pain
  • Bradycardia
  • Clinical triad in right ventricular infarction: hypotension, elevated jugular venous pressure, clear lung fields ^[12]

Classically, it has been taught that STEMI manifests with more severe symptoms than NSTEMI, but this is not always the case.

Follow ACS protocols if acute myocardial ischemia is suspected (see “Acute coronary syndrome”). Diagnosis is based on typical clinical features, ECG findings, and elevation of cardiac biomarkers.

ECG ^[1]

• A 12-lead is the initial test in every patient with suspected myocardial ischemia.
• Findings include pathological Q waves, ST-segment shifts, and T-wave inversions (see “ECG changes in STEMI” and “ECG changes in NSTEMI/unstable angina”).
• Dynamic changes require serial ECG evaluation.
• Compare to prior ECGs (if available).

Localization of myocardial infarct on ECG ^[9][13][14]

Infarction of the anterior wall is caused by obstruction of the LAD or its branches. Depending on the extent of anterior wall infarction, it results in ECG changes in the anterior wall leads (V_1–6) and/or I and aVL. Infarction of the inferior wall is caused by obstruction of the LCX or RCA or their branches, and ECG changes are seen in leads II, III, and aVF.

To remember the ECG leads with maximal ST elevation in anterior MI, think “SAL”: “Septal (V1–2), Apical (V3–4), Lateral (V5–6).

In severe transmural posterior wall infarction, there may not be any ST elevation on a standard 12-lead ECG.

Cardiac biomarkers ^[10][15]

• Cardiac troponin (cTn) is the most important biological marker of myocardial necrosis.
  • Acute myocardial injury: change in cardiac troponin levels in sequential measurements
  • Myocardial injury: cardiac troponin elevation above the 99^thpercentile of the upper reference limit (URL) ^[1]
• All cardiac biomarkers require clinical context for interpretation (e.g., troponin can also be elevated in other cardiac and noncardiac conditions; see “Differential diagnosis of increased troponin”).
• Values and time references may vary based on the precise laboratory methods employed.

Serum troponin T and I are the most important cardiac-specific markers.

The timing of a detectable rise in cardiac troponin levels depends (among other factors) on the assay used by the laboratory.

Additional laboratory studies ^[19][20]

• CBC and markers of inflammation
  • Hemoglobin: to evaluate for anemia
  • Platelets: to evaluate for thrombocytopenia
  • Elevated inflammatory markers: ↑ WBC, CRP
• Serum chemistries
  • Basic metabolic panel: to evaluate for renal dysfunction and electrolyte abnormalities
  • LDH and AST: may be elevated due to cell necrosis
• BNP or NT-proBNP: may be elevated, especially in concurrent heart failure ^[10]
• Coagulation panel: to evaluate for baseline coagulopathies
• Urine toxicology screening: Consider in suspected use of cocaine or methamphetamines. ^[10]

Coronary angiography

• Best test for definitive diagnosis of acute coronary occlusion to identify site and degree of vessel occlusion
• Can be used for concurrent intervention (e.g., PCI; with stent placement)
• Indications include:
  • Acute STEMI
  • NSTEMI with timing depending on risk factors
  • See also “Acute coronary syndrome” and “Cardiac catheterization.”

The most commonly occluded coronary arteries (in descending order): left anterior descending artery, right coronary artery, circumflex artery.

Transthoracic echocardiography ^[1][10]

• Identification of any wall motion abnormalities and assessment of LV function
• Evaluation for complications: aneurysms, mitral valve regurgitation, pericardial effusion, free wall rupture
• Risk assessment: In STEMI, the best predictor of survival is LVEF. ^[12]

Histopathological findings of MI ^[21]

Obstruction of a coronary artery branch due to > 90% stenosis or embolization results in coagulation necrosis of the post-stenotic zone.

Cellular changes

• See “Ischemia” in “Cellular changes and adaptive responses.”
• Reperfusion injury
  • Timing
    • Can occur spontaneously or after revascularization (e.g., fibrinolysis or PCI)
    • Typically occurs when reperfusion occurs > 3 hours after the acute coronary artery occlusion
  • Mechanism: blood flow restored → damaged myocytes release reactive oxygen species (ROS); → mitochondrial permeability transition pores are formed → cell swelling → cell death → Ca²⁺ entry into the cytosol → hypercontraction of myocytes → contraction band necrosis and increase in infarct size ^[22]
  • Microscopic findings: neutrophilic infiltration, capillary obstruction, and contraction band necrosis of the myocardium

References:^[7]

• See “Differential diagnoses of chest pain.”
• See “Differential diagnoses of increased troponin.”
• See “Differential diagnoses of ST elevations on ECG.”

The differential diagnoses listed here are not exhaustive.

This section provides an overview of the most important treatment aspects of myocardial infarction. See “Acute coronary syndrome” for more detailed management.

Any patient with ST elevations on ECG requires immediate evaluation for urgent revascularization. The administration of other therapies should not delay care.

Critical management ^[10][12]

• Revascularization: all patients with suspected acute coronary syndrome should be considered for emergency percutaneous coronary intervention (PCI)
• Monitoring
  • Serial 12-lead ECG
  • Continuous cardiac monitoring
  • Serial serum troponin measurement
• Antiplatelet therapy and anticoagulation: See “Antiplatelet therapy and anticoagulation in STEMI” and “Antiplatelet therapy and anticoagulation in NSTE-ACS.”
  • Dual antiplatelet therapy (DAPT)
    • Aspirin loading dose: 162–325 mg
    • PLUS; ADP receptor inhibitor: prasugrel, ticagrelor, or clopidogrel
  • Anticoagulation: unfractioned heparin or LMWH
• Management of acute complications of myocardial infarction
  • Management of bradycardia
  • Management of tachycardia
  • Management of acute heart failure
  • Management of cardiogenic shock

Adjunctive therapy ^[10][12]

See “Adjunct medical therapy in ACS” for details.

• Oxygen: only in case of cyanosis, severe dyspnea, or SpO₂ < 90% ^[12]
• Sublingual or intravenous nitrate (nitroglycerin or ISDN)
  • For symptomatic relief of chest pain
  • Does not improve prognosis
  • Contraindications: inferior wall infarct (due to risk for hypotension), hypotension, and/or PDE5 inhibitor (e.g., sildenafil) taken within last 24 hours
• Morphine IV or SQ
  • Indicated for severe, persistent chest pain unresponsive to antianginal medication
  • Administer with caution due to the increased risk of complications (e.g., hypotension, respiratory depression) and adverse events.
• Beta blockers (avoid in patients with hypotension, features of acute heart failure, and/or risk of cardiogenic shock): Start within 24 hours.
• Statins: early initiation of high-intensity statin (e.g., atorvastatin) regardless of baseline cholesterol, LDL, and HDL levels
• ACE inhibitors/ARBs: Consider within 24 hours in stable patients with any of the following.
  • STEMI
  • LVEF ≤ 40%
  • Heart failure
  • Hypertension
  • Diabetes mellitus
  • Stable CKD
• Aldosterone antagonists (e.g., eplerenone): Consider in patients already receiving an ACE inhibitor and beta blocker with any of the following.
  • LVEF ≤ 40%
  • Heart failure
  • Diabetes mellitus

Options for initial MI treatment include “MONA-BASH”: Morphine, Oxygen, Nitroglycerin, Antiplatelet drugs (aspirin + ADP receptor inhibitor), Beta blockers, ACE inhibitors, Statins, and Heparin. The scope of interventions depends on the patient's risk profile.

Further management

Further management includes treatment of underlying ischemia (PTCA or CABG) and management of risk factors to prevent recurrence; see also “Prevention of coronary heart disease.”

Prevention of recurrent myocardial infarction ^[10][12]

• Lifestyle modifications for ASCVD prevention (See also “Primary prevention of MI.”)
• Lipid-lowering therapy for ASCVD: All patients should be started on a high-intensity statin (e.g., atorvastatin).
• Antiplatelet therapy
  • Lifelong low-dose aspirin: 75–100 mg/day ^[10][12]
  • Dual antiplatelet therapy (DAPT)
    • Aspirin PLUS one ADP receptor inhibitor (e.g., prasugrel, ticagrelor, clopidogrel)
    • Duration is an individual decision based on bleeding risk and risk of stent thrombosis ^[23]
    • After PCI with stent placement: usually for 12 months
    • See “Antiplatelet therapy and anticoagulation in STEMI” and “Antiplatelet therapy and anticoagulation in NSTE-ACS” for details.
• Management of comorbidities: e.g. treatment of hypertension, management of diabetes mellitus
• Other cardioprotective drugs as indicated
  • Beta blockers: Unless contraindicated, all patients should be started on a beta blocker, which has been shown to confer a mortality benefit.
  • ACE inhibitor/ARB are recommended if any one of the following are present: ; ^[10][12]
    • STEMI (especially those with anterior location)
    • Heart failure
    • LVEF < 40%
    • Hypertension
    • Diabetes mellitus
    • Chronic kidney disease (only if stable)
  • Aldosterone antagonist: in addition to ACE inhibitors in patients with heart failure, LVEF < 40%, or diabetes mellitus

0–24 hours post-infarction ^[6][24]

• Sudden cardiac death (SCD)
  • Definition: A sudden death presumably caused by cardiac arrhythmia or hemodynamic catastrophe, which occurs either within an hour of symptom onset in patients with cardiovascular symptoms, or within 24 hours of being asymptomatic in patients with no cardiovascular symptoms. ^[25][26]
  • Pathophysiology: Fatal ventricular arrhythmia is considered to be the underlying mechanism of SCD. ^[27]
  • Underlying conditions
    • Coronary artery disease: present in ∼ 70% of cases in adults over 35 years ^[28]
    • Dilated/hypertrophic cardiomyopathy
    • Hereditary ion channelopathies (e.g., long QT syndrome, Brugada syndrome)
  • Prevention: installation of the implantable cardioverter-defibrillator device ^[27]
• Arrhythmias: a common cause of death in MI patients in the first 24 hours
  • Ventricular tachyarrhythmias
  • Sinus bradycardia
  • Atrioventricular block (e.g., complete heart block)
  • Conduction blocks
  • Asystole
  • Atrial fibrillation
• Acute left heart failure: death of affected myocardium → absence of myocardial contraction → pulmonary edema
• Cardiogenic shock

1–3 days post-infarction ^[6][24]

• Early infarct-associated pericarditis
  • Typically occurs within the first week of a large infarct close to the pericardium
  • Clinical features of acute pericarditis, including:
    • Friction rub
    • Pleuritic chest pain , dry cough
    • Diffuse ST elevations on ECG
    • Pericardial effusion
  • Treatment: supportive care
  • Complications (rare): hemopericardium, pericardial tamponade
  • Prognosis: usually self-limiting
  • Prevention: early coronary reperfusion therapy

3–14 days post-infarction ^[6][24]

• Papillary muscle rupture
  • Usually occurs 2–7 days after myocardial infarction
  • Can lead to acute mitral regurgitation
  • Location
    • More often: posteromedial papillary muscle rupture due to occlusion of the posterior descending artery (single supply)
    • Less often: anterolateral papillary muscle rupture due to occlusion of LAD and/or LCx (double supply)
  • Clinical features
    • New holosystolic, blowing murmur over the 5^thICS on the midclavicular line
    • Signs of acute mitral regurgitation: dyspnea, cough, bilateral crackles, hypotension
  • Complications: Mitral regurgitation can lead to severe pulmonary edema and/or cardiogenic shock.
• Ventricular septal rupture
  • Usually occurs 3–5 days after myocardial infarction
  • Pathophysiology: macrophagic degradation of the septum → ventricular septal defect → blood flow from LV to RV following the pressure gradient (left-to-right shunt) → ↑ pressure in RV and ↑ O₂ content in the venous blood
  • Most commonly due to LAD infarction (septal arteries arise from LAD)
  • Clinical features
    • New holosystolic murmur over the left sternal border
    • Acute-onset right heart failure (jugular venous distention, peripheral edema)
  • Complications: can progress to cardiogenic shock and severe pulmonary edema
• Left ventricular free wall rupture
  • Usually occurs 5–14 days after myocardial infarction
  • Greatest risk during macrophage-mediated removal of necrotic tissue
  • LV hypertrophy and tissue fibrosis from previous MI decrease the risk of free wall rupture.
  • Clinical features
    • Chest pain
    • Dyspnea
    • Signs of cardiac tamponade (e.g., Beck triad)
  • Complications: cardiac tamponade; , sudden cardiac death (if the rupture occurs acutely)
• Left ventricular pseudoaneurysm: refers to the outpouching of the ventricular wall rupture that is contained by either the pericardium, a thrombus, or scar tissue
  • Usually occurs 3–14 days after myocardial infarction
  • Clinical features
    • Can be asymptomatic
    • If symptomatic
      • New heart murmur
      • Chest pain
      • Heart failure
      • Syncope
  • Complications
    • Rupture → cardiac tamponade (risk of rupture is higher than in a true aneurysm)
    • Associated with mural thromboembolism, decreased cardiac output, and increased risk of arrhythmia

2 weeks to months post-infarction ^[6][24]

• Atrial and ventricular aneurysms
  • Epidemiology: affects 10–20% of patients
  • Clinical features
    • Persistent (> 3 weeks post-MI) ST elevation and T-wave inversions
    • Systolic murmur, S₃ and/or S₄
    • New heart murmur, chest pain, heart failure, and/or syncope
  • Diagnosis: echocardiography
    • Visualization of the pathological myocardial wall protrusion
    • Detection of dyskinetic movements of the thinned aneurysmal wall (uncoordinated contraction occurs due to fibrotic changes of the myocardium)
  • Complications
    • Cardiac arrhythmias (risk of ventricular fibrillation)
    • Rupture → cardiac tamponade
    • Left ventricular thrombus
  • Treatment
    • Anticoagulation if LV thrombus is present
    • Possibly surgery
    • See “Ventricular aneurysm” for details.
• Postmyocardial infarction syndrome (Dressler syndrome): pericarditis occurring 2–10 weeks post-MI without an infective cause
  • Pathophysiology: thought to be due to circulating antibodies against cardiac muscle cells (autoimmune etiology) → immune complex deposition → inflammation
  • Clinical features
    • Signs of acute pericarditis: pleuritic chest pain; , dry cough ; , friction rub
    • Fever
    • Laboratory findings: leukocytosis, ↑ serum troponin levels
    • ECG: diffuse ST elevations
  • Treatment: NSAIDs (e.g., aspirin), colchicine
  • Complications (rare): hemopericardium, pericardial tamponade
• Mural thrombus formation → thromboembolism (stroke, mesenteric ischemia, renal infarction, acute obstruction of peripheral arteries) ^[29]
• Arrhythmias
• Congestive heart failure (e.g., due to ischemic cardiomyopathy)
  • Can occur at any time after an ischemic event
  • Treatment: for patients with LVEF < 40% or signs of heart failure, ACE inhibitor/ARB and aldosterone antagonists have been shown to confer a mortality benefit.
• Reinfarction

We list the most important complications. The selection is not exhaustive.

• Lifestyle modifications for ASCVD prevention ^[12]
  • Smoking cessation
  • Healthy, plant-based diet ^[30]
  • Regular physical activity and exercise
• Management of comorbidities, e.g. treatment of hypertension
• Low-dose aspirin is beneficial for certain high-risk groups. ^[12]
• For detailed information on primary prevention see “ASCVD prevention.”

• One-Minute Telegram 112-2024-1/3: Colchicine for inflammation after MI: not a silver bullet?
• One-Minute Telegram 97-2024-1/3: Beta blockers after MI: no longer a knee-jerk reaction
• One-Minute Telegram 58-2022-2/3: 2022 USPSTF recommendations on statins for primary ASCVD prevention
• One-Minute Telegram 6-2020-3/3: Statins underprescribed in patients with PAD
• One-Minute Telegram 5-2020-3/3: Aspirin discontinuation with continued P2Y₁₂ inhibitors may be beneficial for select patients after PCI

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