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Myocardial Infarction - Comprehensive Clinical Review

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1. Definition & Epidemiology

• 10% occur in people under 40; 45% in people under 65
• Male sex is a risk factor through middle age; postmenopausal women lose estrogen-related protection and IHD becomes the leading cause of death in older females
• STEMI accounts for ~25-30% of ACS cases; its incidence is declining
• Out-of-hospital mortality from STEMI remains ~30%, with one-third of deaths from arrhythmia within the first hour
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511
• Washington Manual of Medical Therapeutics, p. 146

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2. Pathogenesis

Typical Atherothrombotic Mechanism (~90% of cases)

1. Plaque disruption - an atheromatous plaque is eroded or suddenly ruptured by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents
2. Platelet activation - platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin, causing further aggregation and vasospasm
3. Coagulation cascade - activation by tissue factor adds to the growing thrombus
4. Complete occlusion - within minutes the thrombus can fully occlude the lumen

STEMI vs. NSTEMI

• STEMI: Complete, total occlusion of an epicardial coronary artery → full transmural ischemia
• NSTEMI/UA: Partial occlusion or complete occlusion with good collaterals → subendocardial ischemia

Atypical Mechanisms (~10% of cases)

• Vasospasm (cocaine, ephedrine)
• Embolism (from LV mural thrombus, AF, endocarditis, PFO)
• Vasculitis, sickle cell disease, amyloid deposition
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511-512

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3. Anatomy of Infarction

• Isolated RV infarction is unusual (1-3% of cases)
• RCA occlusion extends into the RV in 15-30% of posterior MI cases
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 512

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4. Morphologic Evolution (Pathology)

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 513

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5. Electrocardiographic Changes

• Hyperacute T waves - very earliest finding (minutes)
• ST elevation - hallmark of acute transmural injury; leads opposite the infarct show reciprocal ST depression
• Q wave development - days to weeks; pathological Q = >40 ms wide or >25% of R wave height
• Non-Q-wave infarcts - tend to be less transmural but carry a high risk of re-infarction
• Ganong's Review of Medical Physiology, p. 534

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6. Clinical Presentation & Diagnosis

Typical Presentation

• Severe, crushing/pressure chest pain, often radiating to left arm, jaw, or back
• Diaphoresis, nausea, vomiting
• Dyspnea
• Sense of impending doom

Atypical Presentation (high-risk groups)

• No chest pain (silent MI)
• Confusion, unexplained hypotension, or heart failure as the presenting feature

Diagnostic Triad

1. History - clinical symptoms
2. ECG - ST elevation in ≥2 contiguous leads, or new LBBB
3. Biomarkers - troponin I or T (most sensitive/specific); CK-MB (rises in 4-6 hours, peaks 18-24 hours, normalizes in 3-4 days - useful for re-infarction)

• Washington Manual of Medical Therapeutics, p. 146

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7. Management

Immediate General Measures (MONA + anticoagulation)

• O2 - if SpO2 < 90% or respiratory distress
• Nitrates - vasodilation, reverse vasospasm (avoid in RV infarction, hypotension, or recent PDE5 inhibitor use)
• Antiplatelet therapy - aspirin (loading dose immediately), plus a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel)
• Anticoagulation - unfractionated heparin, LMWH, fondaparinux, or bivalirudin (direct thrombin inhibitor)
• Beta blockers - reduce myocardial O2 demand and arrhythmia risk (avoid if acute HF, cardiogenic shock, bradycardia, or bronchospasm)
• Pain control - morphine (use judiciously; observational data suggest possible harm with opioids in NSTEMI)

Reperfusion - The Central Priority

Secondary Prevention

• High-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg)
• Dual antiplatelet therapy (DAPT) for 12 months post-PCI
• ACE inhibitor/ARB (especially with reduced EF, anterior MI, or diabetes)
• Beta blocker (long-term for reduced EF)
• Aldosterone antagonist (eplerenone/spironolactone) if EF ≤ 40% with HF symptoms
• Cardiac rehabilitation
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 514
• Washington Manual of Medical Therapeutics, p. 147

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8. Complications

Mechanical Complications (Early, within days)

Arrhythmias

• VF - most common cause of death (~50% of mortality), usually within first hour
• VT, heart block (especially inferior MI involving RCA and AV nodal artery), atrial fibrillation, accelerated idioventricular rhythm (reperfusion arrhythmia - generally benign)

Heart Failure

• LV pump failure proportional to mass of damaged myocardium
• Killip classification grades severity (I = no HF → IV = cardiogenic shock)
• Pulmonary edema in severe cases

Later Complications

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 514-515
• Washington Manual of Medical Therapeutics, p. 146-147

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9. Recent Evidence Updates (2024-2025)

• Antiplatelet secondary prevention - A 2025 individual-patient data meta-analysis in The Lancet compared clopidogrel vs. aspirin for secondary prevention of CAD, finding clopidogrel superior to aspirin in several outcomes (PMID 40902613)
• Anticoagulation in AF + stable CAD - A 2025 JACC meta-analysis found that OAC alone (without antiplatelet) may be sufficient in stable coronary disease with AF, avoiding excess bleeding of triple therapy (PMID 39918465)
• Sudden cardiac death post-MI - A 2024 European Heart Journal pooled cohort study found that SCD risk post-MI is highest in the first year, with reduced EF being the dominant predictor (PMID 39378245)

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Summary Table