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Myocardial Infarction (MI)

Definition

• Robbins, Cotran & Kumar Pathologic Basis of Disease

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Classification

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Epidemiology & Risk Factors

• 10% occur in people < 40 years, 45% occur in people < 65 years
• Through middle age, male sex confers higher relative risk
• Females are generally protected during reproductive years; post-menopausal decline in estrogen leads to worsening CAD - IHD is the most common cause of death in older females
• Post-menopausal hormonal replacement therapy has not been shown to be protective and may be detrimental (pro-thrombotic effect)

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Pathogenesis

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 coronary artery lumen

Non-atherothrombotic causes (~10% of MIs)

• Coronary vasospasm (e.g., cocaine, ephedrine use)
• Embolism (from mural thrombus, infective endocarditis vegetations, patent foramen ovale)
• Vasculitis, sickle cell disease, amyloid deposition
• Hemodynamic compromise (shock, severe hypotension)
• Robbins, Cotran & Kumar Pathologic Basis of Disease

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Pathophysiology

1. Seconds - cessation of aerobic metabolism → inadequate ATP and creatine phosphate production → accumulation of lactic acid
2. Within 1 minute - loss of myocardial contractility (before cell death)
3. 20-40 minutes - irreversible cell injury begins (point of no return)
4. 1-2 hours - macroscopic irreversibility without reperfusion

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Morphological Changes Over Time

• Robbins, Cotran & Kumar Pathologic Basis of Disease

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Clinical Features

Symptoms

• Chest pain - the hallmark; typically crushing, pressure-like, or squeezing substernal pain, often radiating to the left arm, left jaw, back, or epigastrium; lasting > 20-30 minutes and not relieved by nitrates
• Dyspnea, diaphoresis, nausea, vomiting
• Silent MI - particularly common in diabetics and elderly (diabetic autonomic neuropathy masks pain); may present as dyspnea, fatigue, or sudden hemodynamic collapse

Signs

• Tachycardia, hypotension (or hypertension early)
• S3/S4 gallop, new mitral regurgitation murmur (papillary muscle dysfunction)
• Signs of heart failure: pulmonary rales, elevated JVP, peripheral edema
• Pericardial friction rub (transmural MI with pericarditis, day 2-3)

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ECG Changes

1. Hyperacute T waves (minutes) - peaked, tall T waves
2. ST elevation (hours) - hallmark of STEMI; leads overlying the infarct show elevation, opposite leads show reciprocal depression
3. T wave inversion (hours to days)
4. Pathological Q waves (days to weeks) - reflect electrically silent dead tissue; indicate transmural necrosis

• Anterior (LAD): V1-V4
• Inferior (RCA): II, III, aVF
• Lateral (LCx): I, aVL, V5-V6
• Posterior: tall R in V1-V2 with ST depression (reciprocal)
• Right ventricle (RCA): ST elevation in right-sided leads (V3R, V4R)
• Ganong's Review of Medical Physiology

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Biomarkers

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Management

Acute Phase - First Response (MONA + Reperfusion)

• Morphine - for pain relief (though evidence for benefit is debated)
• Oxygen - only if SpO₂ < 90% (routine O₂ may be harmful in normoxic patients)
• Nitrates (sublingual/IV nitroglycerin) - for pain and preload reduction; avoid in RV infarction (risk of severe hypotension), and with recent PDE-5 inhibitor use
• Aspirin - 325 mg loading dose immediately; then 75-100 mg daily

Reperfusion Therapy - The Cornerstone of STEMI Management

• Fuster and Hurst's The Heart, 15th Edition

Antithrombotic Therapy

• Aspirin - immediate loading (300-325 mg), then lifelong
• P2Y12 inhibitors (Dual Antiplatelet Therapy - DAPT):
  • Ticagrelor (180 mg loading, 90 mg BD) - preferred
  • Prasugrel (60 mg loading, 10 mg daily) - preferred over clopidogrel post-PCI
  • Clopidogrel (600 mg loading, 75 mg daily) - if others contraindicated
• DAPT is continued for 12 months after ACS; duration may be shortened based on bleeding risk

• Unfractionated heparin (UFH), enoxaparin, bivalirudin, or fondaparinux

Other Pharmacological Therapy

Recent evidence update: A 2025 meta-analysis (PMID: 39298680) found that beta-blockers for secondary prevention after MI in patients without reduced ejection fraction or heart failure may have limited benefit, challenging the traditional universal use of beta-blockers post-MI in this subgroup.

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Complications

Early (hours to days)

1. Arrhythmias - most common complication; ~90% of patients develop some form
   • Ventricular fibrillation - greatest risk in the first hour (most dangerous)
   • Complete heart block (especially inferior MI with RCA occlusion)
   • Sinus bradycardia (inferior MI)
   • Atrial fibrillation
2. Cardiogenic shock - LV pump failure; carries high mortality (~50%)
   • Defined as hypotension + signs of tissue hypoperfusion despite adequate filling
3. Acute heart failure - pulmonary edema from LV systolic failure

Days to Weeks

1. Myocardial rupture (1-3% of MIs, usually day 3-7)
   • Free wall rupture → hemopericardium → cardiac tamponade (usually fatal)
   • Ventricular septal rupture → VSD with acute left-to-right shunt
   • Papillary muscle rupture → severe acute mitral regurgitation
   • Risk factors: first MI, female sex, age > 60, anterior/lateral wall, no prior LVH
2. Pericarditis - fibrinous; appears 2-3 days post-MI (friction rub, pleuritic chest pain)
3. Dressler syndrome (weeks to months) - immune-mediated pericarditis due to anti-myocardial antibodies
4. LV aneurysm - thinning and outward bulging of infarcted wall; predisposes to:
   • Mural thrombus → systemic embolization
   • Persistent ST elevation
   • Refractory heart failure
   • Ventricular arrhythmias
5. Mural thrombus - forms on akinetic/dyskinetic endocardium → stroke risk

• Robbins, Cotran & Kumar Pathologic Basis of Disease, Fig. 12.17

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Killip Classification (Clinical Severity)

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Secondary Prevention (Post-Discharge)

• DAPT: Continue for 12 months; aspirin lifelong thereafter
• High-intensity statin: Atorvastatin 80 mg or rosuvastatin 40 mg; target LDL < 70 mg/dL (or < 55 mg/dL in very high-risk)
• ACE inhibitor/ARB: Especially if EF < 40%, hypertension, or diabetes
• Beta-blocker: If EF < 40% or ongoing ischemia
• Cardiac rehabilitation: Strongly recommended
• Lifestyle modification: Smoking cessation, diet, exercise, weight management

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Key Images from Textbooks

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• Robbins, Cotran & Kumar Pathologic Basis of Disease (Robbins Pathology), Chapter 12
• Fuster and Hurst's The Heart, 15th Edition, Chapter 18
• Ganong's Review of Medical Physiology, 26th Edition, Chapter 29
• Braunwald's Heart Disease, 2-Vol Set