Myocardial Infarction - Complete Overview

Definition

Epidemiology & Risk Factors

• ~10% of MIs occur before age 40; ~45% before age 65
• Men are at greater risk than women, but the gap narrows with age
• Women are relatively protected during reproductive years; risk rises sharply after menopause (declining estrogen)
• Major risk factors mirror those for atherosclerosis: hypertension, dyslipidemia, diabetes, smoking, obesity, family history

Types of MI

• Type 1 MI - atherosclerotic plaque rupture causing occlusion and ischemic infarction (the classic "heart attack")
• Type 2 MI - demand ischemia; mismatch between oxygen supply and demand without plaque rupture (e.g., tachyarrhythmia, severe anemia, hypotension)

• STEMI - ST elevation + biomarker elevation (complete occlusion)
• NSTEMI - biomarker elevation without ST elevation (partial/transient occlusion)
• Unstable angina - ischemic symptoms without biomarker elevation

Pathogenesis

1. An atheromatous plaque is eroded or disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic contents
2. Platelets adhere, aggregate, and activate, releasing thromboxane A2, ADP, and serotonin - causing further aggregation and vasospasm
3. Coagulation is activated by exposure of tissue factor, adding to the thrombus
4. Within minutes, the enlarging thrombus fully occludes the coronary lumen

Angiography within 4 hours of MI onset shows coronary thrombosis in ~90% of cases. When performed at 12-24 hours, only 60% still show thrombus - indicating spontaneous thrombolysis occurs.

Myocardial Response to Ischemia

• Within seconds: aerobic metabolism ceases → ATP drops → lactic acid accumulates
• Within minutes: loss of contractility (reversible at this stage)
• 20-40 minutes of persistent ischemia: irreversible coagulative necrosis
• The subendocardial zone is most susceptible - it receives blood last from epicardial vessels and is compressed by high intramural pressures

Coronary Artery Territories

Morphological Evolution

Key point: Myocardial necrosis proceeds invariably to scar without regeneration.

ECG Changes

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

Cardiac Biomarkers

• Troponin I and T - most sensitive and specific; rise 3-6 hours post-MI, peak at 24-48h, remain elevated 7-10 days (troponin T) or 5-7 days (troponin I)
• CK-MB - rises in 4-6h, peaks at 24h, returns to normal in 48-72h; used to detect re-infarction
• Myoglobin - earliest to rise (1-3h) but not cardiac-specific

Clinical Presentation

• Severe, crushing/pressure chest pain - often radiating to the left arm, jaw, or back
• Duration >20 minutes (differentiates from stable angina)
• Diaphoresis, nausea, vomiting
• Dyspnea

• Epigastric pain, fatigue, jaw pain, or no pain at all ("silent MI")

Management

Acute STEMI - "Time is muscle"

1. Immediate reperfusion (within 90 min "door-to-balloon"):
   • Primary PCI (preferred if available within 90 min)
   • Thrombolysis (if PCI unavailable within 120 min)
2. Antiplatelet therapy:
   • Aspirin 300 mg loading
   • P2Y12 inhibitor (ticagrelor or clopidogrel)
3. Anticoagulation: heparin (UFH or LMWH)
4. Supplemental O2 if SpO2 <94%
5. Nitrates: sublingual/IV for chest pain and hypertension (avoid in RV infarction - can cause catastrophic preload reduction)
6. Beta-blockers: cardioprotective; start if no cardiogenic shock, bradycardia, or low EF
7. Morphine: for pain unrelieved by nitrates

NSTEMI / Unstable Angina

• Risk-stratify (TIMI/GRACE score)
• High-risk: early invasive strategy (angiography within 24-72h)
• Medical therapy: antiplatelet + anticoagulation + statin

Secondary Prevention

• Aspirin lifelong
• Statin (high-intensity, e.g., atorvastatin 40-80 mg)
• ACE inhibitor / ARB - especially if EF reduced or anterior MI; prevents remodeling
• Beta-blocker - reduces sudden cardiac death
• Aldosterone antagonist (eplerenone) if EF <40% and no renal failure

Recent meta-analysis (Chi et al., 2025) found beta-blockers for secondary prevention post-MI may not reduce mortality in patients without reduced ejection fraction or heart failure - an evolving evidence area.

Complications

Early (within days)

• Arrhythmias - most common cause of death; ventricular fibrillation accounts for 80-90% of ischemic cardiac deaths
• Cardiogenic shock - pump failure; mortality ~80% without intervention
• Acute heart failure - pulmonary edema from LV dysfunction
• Systolic stretch - non-contractile infarcted segment bulges outward during systole, worsening effective output

Mechanical complications (days 1-14, highest risk 3-7 days)

• Free wall rupture - leads to hemopericardium and tamponade; usually fatal
• Interventricular septal rupture - new harsh pansystolic murmur; requires surgical repair
• Papillary muscle rupture - acute severe mitral regurgitation; cardiogenic shock

Late complications

• Ventricular aneurysm - fibrotic bulge of infarcted wall; risk of mural thrombus, arrhythmia, and persistent heart failure
• Dressler syndrome (post-MI pericarditis) - autoimmune pericarditis 2-10 weeks post-MI; fever, pleuritic chest pain, elevated ESR; treated with NSAIDs/aspirin
• Chronic heart failure - progressive LV remodeling
• Sudden cardiac death - Peek et al., 2024 found in a meta-analysis of pooled cohorts that sudden cardiac death risk remains significantly elevated for years after MI

Key Pearls

• Irreversible injury begins at 20-40 minutes of ischemia
• Full infarct develops in 3-6 hours - the reperfusion window
• LAD occlusion = most common (40-50%); often fatal if proximal
• Subendocardium is always more vulnerable than epicardium
• ECG: ST elevation = acute injury; Q waves = established necrosis
• Right-sided MI: avoid nitrates and diuretics; maintain preload
• Cardiac troponin is the gold standard biomarker
• After MI, healing produces only scar - no myocardial regeneration