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Myocardial Infarction (MI)

Definition

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Epidemiology & Risk Factors

• ~10% of MIs occur before age 40; 45% occur before age 65
• Male sex increases relative risk through middle age
• Women are relatively protected during reproductive years; this protection is lost after menopause (declining estrogen - rise in inflammatory markers, cholesterol, BP)
• IHD is the most common cause of death in older adult women
• Key risk factors: atherosclerosis, hypertension, diabetes, dyslipidemia, smoking, family history, obesity

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Pathogenesis

Coronary Arterial Occlusion

1. An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces - exposing subendothelial collagen and necrotic plaque contents to blood
2. Platelets adhere, aggregate, and are activated - releasing thromboxane A2, ADP, and serotonin - causing further platelet aggregation and vasospasm
3. Coagulation is activated by tissue factor - adding to the growing thrombus
4. Within minutes, the thrombus can completely occlude the coronary artery lumen

Uncommon Causes (10% of MIs)

• Vasospasm (with or without atherosclerosis) - e.g., cocaine or ephedrine
• Embolism (from AF mural thrombus, valve vegetations, prosthetic material)
• Small vessel disease (vasculitis, amyloid, sickle cell)
• Shock / severe hypertrophy with demand ischemia

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Myocardial Response to Ischemia

Timeline of Events (Robbins, Cotran & Kumar, Table 12.4)

Necrosis Progression

• Last to receive blood from epicardial vessels
• Exposed to the highest intramural pressures (impeding inflow)

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Coronary Artery Distribution & Infarct Location

• In right-dominant circulation (~80% of individuals), the RCA perfuses the posterior septum
• RCA occlusions may extend into the RV wall in 15-30% of cases
• Isolated RV infarction is rare (1-3%)

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Morphological Changes Over Time

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Cardiac Biomarkers

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Classification

By ECG Pattern

• STEMI (ST-Elevation MI): complete coronary occlusion; transmural ischemia; ST elevation in leads overlying infarct
• NSTEMI (Non-ST-Elevation MI): partial occlusion or spontaneous reperfusion; subendocardial ischemia; no ST elevation (may show ST depression, T-wave changes, or normal ECG)

By Depth

• Transmural: full-thickness necrosis from endocardium to epicardium (usually corresponds to STEMI)
• Subendocardial: limited to inner 1/3-1/2 of wall (usually corresponds to NSTEMI)

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ECG Changes

Evolution of ECG Changes

• Acute (minutes-hours): Hyperacute T-waves → ST elevation ("tombstone" pattern)
• Evolving (hours-days): ST normalizes, T-wave inversion develops
• Old/healed: Pathological Q waves (dead tissue electrically silent; area negative during systole) - persist indefinitely
• Leads on the opposite side of the heart show reciprocal ST depression

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Clinical Features

• Severe, crushing, pressure-like chest pain - often radiating to left arm, jaw, shoulder, or back
• Not relieved by nitrates (unlike stable angina)
• Associated: diaphoresis, nausea/vomiting, dyspnea, sense of impending doom
• Silent MI occurs in ~20-25% (especially diabetics and the elderly)

• Hypotension (cardiogenic shock), pallor, diaphoresis
• S3 gallop (LV dysfunction), S4
• New murmur (papillary muscle rupture, VSD)
• Pericardial friction rub (pericarditis)
• Jugular venous distension + clear lungs + hypotension = RV infarction triad

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Management

Immediate Initial Steps

1. Aspirin 160-325 mg (chewed for rapid absorption) - inhibits COX-1 and reduces thromboxane A2 (Harrison's Principles, p. 1203)
2. O2 supplementation only if SpO2 < 90%
3. Nitroglycerin (sublingual 0.4 mg x3, q5 min) - reduces preload and dilates coronaries; avoid if: SBP <90 mmHg, RV infarction, or PDE-5 inhibitor use within 24h
4. Morphine 2-4 mg IV q5 min for pain unresponsive to nitrates
5. Beta-blocker (e.g., metoprolol 5 mg IV q2-5 min x3 doses if HR >60, SBP >100, no heart block) - reduces O2 demand, lowers risk of VF and reinfarction

Reperfusion Strategy (STEMI) - the cornerstone of treatment

• Primary PCI (preferred): target door-to-balloon time ≤90 minutes, or ≤120 minutes from first medical contact; preferred if available
  • Indications: STEMI or new LBBB within 12h of symptom onset (or >12h if symptoms persist); cardiogenic shock in patients <75 years
  • Requires centers performing >400 PCIs/year with cardiac surgery backup
• Fibrinolysis: if primary PCI cannot be performed within 120 min; must follow with angiography within 3-24h (pharmacoinvasive strategy)
  • Avoid if active bleeding, prior intracranial hemorrhage, BP >180/110, recent surgery/trauma

Antithrombotic Therapy

• Dual antiplatelet therapy (DAPT): Aspirin + P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel for STEMI)
• Anticoagulation: Unfractionated heparin, low-molecular weight heparin, bivalirudin, or fondaparinux

Long-term Secondary Prevention

• Beta-blockers: reduce mortality; use indefinitely post-MI with reduced EF
• ACE inhibitors / ARBs: reduce LV remodeling; start within 24h; especially if EF <40%, hypertension, or diabetes
• Statins: high-intensity therapy (atorvastatin 40-80 mg); start immediately regardless of baseline LDL
• Aldosterone antagonist (eplerenone/spironolactone): if EF ≤40% with HF or diabetes, and no significant renal failure or hyperkalemia
• DAPT continued for 12 months post-stenting

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Complications

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Recent Evidence Update

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