Myocardial Infarction (MI)

1. Definition & Epidemiology

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511

2. Pathogenesis

Coronary Arterial Occlusion (Typical - 90% of cases)

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. Activation of coagulation by tissue factor adds to the growing thrombus.
4. Within minutes, the thrombus completely occludes the coronary artery lumen.

Atypical Causes (~10% of cases)

• Vasospasm (with or without atherosclerosis) - e.g., cocaine, ephedrine use
• Emboli from mural thrombus, infective endocarditis vegetations, or patent foramen ovale
• Vasculitis, sickle cell disease, amyloid deposition in vessel walls
• Robbins, Cotran & Kumar, p. 511

Myocardial Response to Ischemia

• Robbins, Cotran & Kumar, p. 512
• Guyton and Hall Textbook of Medical Physiology, p. 271

3. Patterns of Infarction

• Transmural infarction: Full-thickness necrosis of the ventricular wall; caused by complete occlusion of an epicardial vessel. Associated with STEMI on ECG.
• Subendocardial (non-transmural) infarction: Necrosis limited to the inner third of the ventricular wall; occurs with transient/partial obstruction or global hypotension. Associated with NSTEMI/UA on ECG.

Coronary Artery Territory

4. Morphological Evolution (Gross & Microscopic)

• Robbins, Cotran & Kumar Pathologic Basis of Disease

5. Clinical Features

Symptoms

• Chest pain (most common): crushing/squeezing substernal pressure that may radiate to left arm, jaw, neck, or back. Typically lasting > 20-30 minutes and not relieved by rest or nitrates.
• Associated symptoms: diaphoresis, nausea/vomiting, dyspnea, lightheadedness, sense of impending doom.
• Silent MI (no pain): especially in diabetics (due to neuropathy) and the elderly - may present only with dyspnea, fatigue, or syncope.

ECG Changes

• Hyperacute phase: tall peaked T waves
• Acute phase (minutes to hours): ST segment elevation in leads overlying infarction (STEMI); reciprocal ST depression in opposite leads
• Days to weeks: T wave inversions develop; ST gradually normalizes
• Weeks later: Q waves appear (electrically silent scar) - "pathological Q waves" (>40ms wide, >25% of QRS height)
• Ganong's Review of Medical Physiology, p. 534

Biomarkers

6. Classification: STEMI vs. NSTEMI

7. Management

Immediate (All ACS)

• Oxygen (if SpO2 < 90%)
• Aspirin 300 mg loading dose (antiplatelet, irreversible COX-1 inhibition)
• P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) for dual antiplatelet therapy (DAPT)
• Anticoagulation: heparin (UFH or LMWH)
• Nitrates for pain relief (avoid in RV infarction or hypotension)
• Morphine for refractory pain (used cautiously - may delay P2Y12 absorption)
• Beta-blockers (early oral, if no contraindications - reduces heart rate and oxygen demand)

STEMI - Reperfusion Therapy

• Primary PCI (percutaneous coronary intervention): preferred if available within 90 minutes of first medical contact ("door-to-balloon time"). Angioplasty ± stenting directly opens the occluded artery.
• Fibrinolysis (thrombolysis): if PCI is not available within 120 minutes. Agents: alteplase, tenecteplase, streptokinase. Effective if given within 12 hours of symptom onset.
• The benefit of reperfusion is greatest when achieved quickly - this is the rationale for the "time is muscle" principle, since only severe ischemia lasting 20-40 minutes or longer causes irreversible necrosis.

NSTEMI/UA - Medical Management + Early Invasive Strategy

• Risk stratification using GRACE or TIMI score
• Early invasive angiography (within 24-48 hours) for high-risk patients

Long-term Secondary Prevention

• Aspirin lifelong
• P2Y12 inhibitor (DAPT for 12 months post-ACS, then reassessed)
• Statin (high-intensity, e.g., atorvastatin 40-80 mg)
• ACE inhibitor / ARB (reduces LV remodeling, especially if reduced EF)
• Beta-blocker (reduces mortality post-MI, especially with reduced EF)
• Aldosterone antagonist (eplerenone/spironolactone if EF < 40% with symptoms)

Recent Evidence Note: A 2025 meta-analysis (PMID 39298680) questions the routine use of beta-blockers for secondary prevention in post-MI patients without reduced ejection fraction or heart failure, suggesting the benefit may be less clear in this subgroup - a potential update to classic teaching.

8. Causes of Death

1. Decreased cardiac output - systolic dysfunction; the non-contracting infarcted zone paradoxically bulges outward ("systolic stretch"), worsening overall pump function. Cardiogenic shock occurs when >40% of LV mass is infarcted.
2. Pulmonary edema - from LV failure causing blood to dam back into pulmonary circulation.
3. Ventricular fibrillation - the most common cause of sudden cardiac death in the first few hours; due to electrical instability in peri-infarct zone.
4. Cardiac rupture - most common 3-7 days post-MI when necrotic tissue is softest; can cause hemopericardium and tamponade.

• Guyton and Hall Textbook of Medical Physiology, p. 271

9. Complications

Early (hours to days)

• Arrhythmias: VF, VT, heart block (especially with inferior MI and RCA occlusion), AF
• Cardiogenic shock: poor prognosis; mortality 50-80% without intervention
• Acute mitral regurgitation: from papillary muscle rupture (typically posteromedial papillary, day 2-7)
• Free wall rupture: pericardial tamponade, rapid death
• Ventricular septal defect (VSD): septal rupture, leads to acute left-to-right shunt
• Right ventricular infarction (with inferior STEMI): hypotension, elevated JVP, clear lungs

Late (days to weeks)

• Dressler syndrome (post-MI pericarditis): autoimmune reaction, occurs 2-10 weeks post-MI
• Left ventricular aneurysm: dyskinetic wall segment; risk of mural thrombus and systemic embolism
• Heart failure / dilated cardiomyopathy: from extensive infarction and adverse LV remodeling
• Sudden cardiac death from recurrent arrhythmias

Summary Diagram of Pathophysiology

Atherosclerotic plaque rupture
        ↓
Platelet aggregation + thrombus
        ↓
Coronary artery occlusion
        ↓
Ischemia → ATP depletion (seconds)
        ↓
Loss of contractility (< 2 min)
        ↓
Irreversible necrosis (20-40 min) → "Time is muscle"
        ↓
Coagulation necrosis → Scar formation (weeks)
        ↓
Complications (arrhythmias, pump failure, rupture, remodeling)

• Robbins, Cotran & Kumar - Pathologic Basis of Disease, Ch. 12 (Pathogenesis, morphology, epidemiology)
• Guyton & Hall Textbook of Medical Physiology (Physiology, causes of death)
• Ganong's Review of Medical Physiology (ECG changes)
• Robbins & Kumar Basic Pathology (Overview)
• Beta-blockers post-MI meta-analysis, Eur J Prev Cardiol 2025 (Updated evidence on secondary prevention)