Myocardial Infarction (MI)

Definition

Epidemiology

Classification (Fourth Universal Definition - 5 Types)

STEMI vs. NSTEMI

• STEMI (ST-Elevation MI): Complete occlusion; transmural injury; ST elevation on ECG
• NSTEMI (Non-ST-Elevation MI): Partial/transient occlusion; subendocardial injury; no ST elevation but troponin elevated
• Unstable angina: Plaque disruption + thrombus, but no biomarker rise; increasingly treated aggressively

Pathophysiology

Coronary Artery Occlusion - Step by Step

1. Atheromatous plaque eroded or disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces - exposing subendothelial collagen and necrotic plaque contents
2. Platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin - promoting further aggregation and vasospasm
3. Coagulation cascade activated by tissue factor exposure - thrombin converts fibrinogen to fibrin
4. Glycoprotein IIb/IIIa receptors on platelets develop high affinity for fibrinogen - cross-linking platelets
5. Within minutes, the thrombus may completely occlude the coronary lumen
6. Angiography within 4 hours of MI onset demonstrates coronary thrombosis in ~90% of cases

Cellular Response to Ischemia

• Within seconds: aerobic metabolism ceases; ATP drops; potentially noxious metabolites (lactic acid) accumulate
• Within minutes: loss of contractility (reversible at this stage)
• After 20-40 minutes of persistent ischemia: irreversible damage and coagulative necrosis
• Earliest detectable necrosis: sarcolemmal membrane disruption - intracellular macromolecules leak into circulation
• If blood flow restored before irreversible injury: myocardium preserved ("stunned myocardium" - transiently noncontractile for days)
• In 80-90% of cardiac deaths: cause is ventricular fibrillation from myocardial irritability, not pump failure

Subendocardial Vulnerability

1. It is the last area to receive blood from epicardial vessels
2. It is exposed to relatively high intramural pressures that impede blood inflow
3. It has higher oxygen consumption

Coronary Artery Territories and Infarct Patterns

FIG. 9.9 - Dependence of myocardial infarction on coronary artery territory. Robbins & Kumar Basic Pathology

• Right dominant circulation (90% of individuals): RCA gives rise to posterior descending artery
• 15-30% of posterior/posteroseptal MIs also extend into the right ventricle
• Isolated RV infarction: only 1-3% of IHD cases

Morphological Timeline

FIG. 9.10 - Acute MI of posterolateral LV demonstrated by lack of TTC staining in necrotic area (arrow); old scar (arrowhead); ventricular rupture site (asterisk). Robbins & Kumar Basic Pathology, p. 357

ECG Changes

• Acute STEMI: ST elevation in leads overlying the infarct; reciprocal ST depression in opposite leads
• Evolving: After days-weeks, ST changes subside; dead muscle electrically silent
• Old MI: Q waves (pathological) appear in relevant leads ("Q-wave MI"); reflects lack of normal depolarization vector
• Non-Q-wave MI (NSTEMI): Tends to be less transmural but carries high risk of early reinfarction

Clinical Presentation

Symptoms

• Chest pain: Heavy, crushing, pressure-like; substernal; radiates to left arm, jaw, neck, back
• Duration: >20-30 minutes (unlike angina)
• Associated: Diaphoresis, nausea/vomiting, dyspnea, sense of impending doom
• Atypical presentations (especially in women, elderly, diabetics): Epigastric pain, fatigue, syncope, silent MI

Signs

• Anxiety, diaphoresis, pallor
• Tachycardia or bradycardia (especially inferior MI - vagal)
• S3 or S4 gallop
• New murmur (papillary muscle dysfunction, VSD)
• Pulmonary crackles (if LV failure)
• Hypotension (cardiogenic shock)

Biomarkers

Causes of Death After AMI

1. Decreased cardiac output - "systolic stretch" (ischemic zone bulges during systole instead of contracting - reduces net pumping efficiency) - Guyton & Hall, p. 271
2. Pulmonary edema - damming of blood in pulmonary vessels
3. Ventricular fibrillation - most common cause; majority of VF deaths within first 24h (half in first hour)
4. Cardiac rupture (rare but catastrophic) - usually ventricular free wall, papillary muscles, or interventricular septum at 3-7 days

Complications

Management

Prehospital

• Immediate aspirin (if no contraindication)
• Rapid transport to PCI-capable center
• Defibrillator available (most out-of-hospital deaths = VF in first hour)
• Prehospital fibrinolysis in remote settings if ECG-confirmed STEMI and trained personnel

Emergency Department - Initial Medications

• Morphine (IV for pain, reduces sympathetic drive)
• Oxygen (if SpO2 <90%)
• Nitroglycerin (IV if BP >90 mmHg systolic; avoid in RV infarction and phosphodiesterase inhibitor use)
• Aspirin (162-325 mg, chewed, immediately) - Tintinalli's EM
• P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel)
• Anticoagulation (unfractionated heparin, LMWH, or bivalirudin)
• Beta-blockers (oral; avoid if cardiogenic shock risk, acute decompensation, or significant bradycardia)
• ACE inhibitors (begin within 24h if no hypotension/renal failure - reduce LV remodeling)
• Statins (high-intensity: atorvastatin 40-80 mg)

Reperfusion Strategy

• Superior to fibrinolysis in reducing mortality, reinfarction, and stroke
• Door-to-balloon time target: <90 minutes
• Greatest benefit in: age <75, no prior MI, anterior STEMI

• Acceptable within 12 hours of symptom onset (most benefit within 3 hours)
• Agents: Alteplase (tPA), reteplase, tenecteplase (TNK)
• Contraindications: recent surgery/stroke, active bleeding, hypertensive emergency

Cardiogenic Shock Management

• Mechanical circulatory support (IABP, Impella) as bridge to revascularization
• Emergency PCI or CABG for definitive treatment of cardiogenic shock

Secondary Prevention (Post-MI)

• Dual antiplatelet therapy (aspirin + P2Y12) for 12 months
• Beta-blockers (for at least 3 years post-MI; recent 2025 meta-analysis questions benefit in preserved EF without HF - PMID 39298680)
• ACE inhibitor or ARB (especially if EF reduced or DM)
• Aldosterone antagonist (if EF <40% + DM or HF)
• High-intensity statin (target LDL-C <55 mg/dL)
• Cardiac rehabilitation, lifestyle modification, smoking cessation

Recent Evidence Update