Myocardial Infarction (MI)

Definition

Epidemiology

• ~800,000 MIs per year in the United States (nearly one every 40 seconds)
• ~400,000 deaths annually from MI
• 10% of MIs occur before age 40; 45% before age 65
• Men are at higher risk during middle age; women lose their relative protection after menopause due to falling estrogen and rising inflammatory markers, cholesterol, and blood pressure
• IHD (ischemic heart disease) is the most common cause of death in older women
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511

Pathogenesis

Typical Sequence (>90% of cases)

1. Plaque disruption - An atheromatous plaque is eroded or ruptured by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to circulating blood
2. Platelet activation - Platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin, driving further platelet aggregation and vasospasm
3. Coagulation cascade - Tissue factor exposure activates coagulation, adding to the growing thrombus
4. Complete occlusion - Within minutes, the enlarging thrombus can completely occlude the coronary artery lumen

Atypical Causes (~10% of cases)

• Vasospasm - with or without atherosclerosis; may be triggered by cocaine, ephedrine, or catecholamines
• Embolism - from left atrial mural thrombus (AF), valve vegetations, prosthetic material, or paradoxical emboli via patent foramen ovale
• Microinfarction - vasculitis, amyloid deposition, sickle cell disease (small intramural vessel pathology)
• Subendocardial ischemia without occlusion - prolonged hypoperfusion/tachycardia on top of fixed coronary stenoses

Types of Infarction by Distribution

Robbins, Cotran & Kumar - Fig. 12.11: Distribution of necrosis by vessel territory

Morphological Changes (Timeline)

• Coagulative necrosis with preservation of cell outlines (ghosts)
• Contraction band necrosis in reperfused infarcts - intense eosinophilic cross bands due to calcium influx causing hypercontracted sarcomeres stuck in tetanus without ATP
• Stunned myocardium - prolonged contractile dysfunction of salvaged (still viable) myocytes that gradually recovers
• Hibernating myocardium - chronically reduced function due to sublethal ischemia, recoverable with revascularization

ECG Changes

• Acute phase: ST segment elevation in leads over the infarct; ST depression in reciprocal leads
• Later (days-weeks): ST normalizes; Q waves appear (infarcted muscle is electrically silent and fails to contribute positivity)
• Non-Q-wave infarcts: Less severe but higher risk of subsequent reinfarction
• Ganong's Review of Medical Physiology, p. 534

• Anterior MI (LAD): V1-V4
• Lateral MI (LCX): I, aVL, V5-V6
• Inferior MI (RCA): II, III, aVF
• Posterior MI (RCA/LCX): Tall R in V1-V2, ST depression V1-V2 (reciprocal)

Clinical Features

• Chest pain: Prolonged (>30 min), crushing/squeezing/stabbing, often radiates to left arm, jaw, or neck
• Diaphoresis: Profuse sweating
• Nausea/vomiting: Particularly with inferior MI (vagal stimulation)
• Dyspnea: Due to impaired LV contractility and pulmonary congestion
• Rapid, weak pulse
• Silent MI: Up to 25% of cases - especially in diabetics (autonomic neuropathy); discovered only by ECG or biomarkers
• Robbins, Cotran & Kumar, p. 516

Diagnosis

Biomarkers

Leukocytosis

Complications

Cardiac Causes of Death

1. Decreased cardiac output / Cardiogenic shock
   • Occurs when >40% of LV is infarcted
   • "Systolic stretch": ischemic/dead muscle bulges outward during systole instead of contracting, dissipating pump energy
   • Mortality 40-50% once cardiogenic shock develops
2. Pulmonary edema
   • Blood dams back into pulmonary vasculature
   • Reduced renal output leads to fluid retention over days, precipitating acute pulmonary edema
3. Ventricular fibrillation
   • Most common cause of sudden death
   • Two dangerous windows: within 10 minutes, then again at ~1 hour post-infarct
   • Mechanisms: K+ loss raises extracellular K+ (increased irritability), injury currents, sympathetic reflexes, and ischemia-lengthened refractory periods creating re-entry
4. Cardiac rupture
   • Free wall rupture (hemopericardium/tamponade): days 4-7 during macrophage-mediated softening
   • Papillary muscle rupture: acute mitral regurgitation
   • Ventricular septal defect: new harsh systolic murmur

Other Complications

Management Overview

Acute Phase (STEMI)

1. Aspirin + P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) - dual antiplatelet therapy
2. Anticoagulation (heparin / LMWH / bivalirudin)
3. Primary PCI (percutaneous coronary intervention) - preferred reperfusion if available within 90 min
4. Fibrinolysis - if PCI not available within 120 min of first medical contact
5. Nitrates - pain relief, preload reduction
6. Morphine - analgesia (though evidence now suggests caution due to possible platelet interaction)
7. Beta-blockers - reduce myocardial oxygen demand, antiarrhythmic
8. Oxygen - only if SpO2 <90%

Secondary Prevention

• Beta-blockers: Traditionally given post-MI; a 2025 meta-analysis found that in patients without reduced EF or heart failure, the benefit of long-term beta-blockers is uncertain - this challenges conventional practice
• ACE inhibitors/ARBs: Reduce remodeling, especially with reduced EF
• High-intensity statins: Plaque stabilization and LDL lowering
• Aldosterone antagonists (eplerenone/spironolactone): In patients with EF <40% + HF or diabetes
• ICD: If EF remains <35% after 40+ days

Recent Evidence Update

• Beta-blockers post-MI without reduced EF (2025 meta-analysis, PMID 39298680): Challenges routine long-term beta-blocker use in preserved EF post-MI patients
• Sudden cardiac death post-MI (2024, PMID 39378245): Individual participant data from pooled cohorts characterizing SCD risk stratification after MI

• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th ed.), pp. 511-516
• Robbins & Kumar Basic Pathology, pp. 467-471
• Ganong's Review of Medical Physiology (26th ed.), pp. 534-536
• Guyton & Hall Textbook of Medical Physiology, pp. 271-273
• Braunwald's Heart Disease (12th ed.)