Myocardial Infraction
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"myocardial infarction"[MeSH Terms] AND management
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Myocardial Infarction (MI)
Definition
Myocardial infarction (MI) - commonly called a "heart attack" - is necrosis of cardiac muscle resulting from prolonged ischemia. The 2018 Fourth Universal Definition (joint U.S./European Cardiology Task Force) defines it as "the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia."
- Approximately 800,000 MIs occur in the United States each year (nearly one every 40 seconds)
- ~400,000 deaths annually
- 10% occur in people under age 40; 45% occur under age 65
- Male sex increases risk through middle age; postmenopausal women lose estrogen protection and IHD becomes the most common cause of death in older women
(Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511; Robbins & Kumar Basic Pathology, p. 467)
Etiology & Risk Factors
The major underlying cause is coronary atherosclerosis. Risk factors include:
| Category | Factors |
|---|---|
| Non-modifiable | Age, male sex (pre-menopause), family history, genetics |
| Modifiable | Hypertension, hyperlipidemia, diabetes, smoking, obesity, sedentary lifestyle |
| Special | Cocaine/ephedrine use (vasospasm), hypercoagulable states, atrial fibrillation (embolism) |
Pathogenesis
Classic Atherothrombotic Sequence (90% of cases)
- 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 to blood
- Platelet activation - Platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin, causing further platelet aggregation and vasospasm
- Coagulation cascade - Tissue factor exposure activates coagulation, adding to the growing thrombus
- Complete occlusion - Within minutes, the thrombus can completely occlude the coronary artery lumen
Angiography performed within 4 hours of symptom onset demonstrates coronary thrombosis in ~90% of cases. By 12-24 hours, evidence drops to 60% (spontaneous lysis occurs). This is the therapeutic rationale for early thrombolysis and/or angioplasty.
Non-Atherothrombotic Causes (~10% of cases)
- Coronary vasospasm (with or without atherosclerosis) - cocaine, ephedrine
- Embolism (from left atrial thrombus in AF, valve vegetations, prosthetic material)
- Vasculitis of small intramural coronary vessels
- Hematologic disorders (sickle cell disease, hypercoagulable states)
- Amyloid deposition in vascular walls
(Robbins & Kumar Basic Pathology, p. 468-471)
Coronary Artery Territory and Infarct Location
| Artery | Frequency | Area of Infarction |
|---|---|---|
| Left Anterior Descending (LAD) | 40-50% | Anterior LV wall near apex; anterior ventricular septum; apex circumferentially |
| Right Coronary Artery (RCA) | 30-40% | Inferior/posterior LV wall; posterior ventricular septum; inferior/posterior RV (in some cases) |
| Left Circumflex (LCx) | 15-20% | Lateral LV wall (except apex) |
- Isolated RV infarction: only 1-3% of cases
- 15-30% of RCA obstructions extend into the RV wall
(Robbins, Cotran & Kumar, p. 512)
Morphological Changes Over Time
The gross and microscopic appearance changes in a predictable sequence:
| Time After MI | Gross Appearance | Histologic Changes |
|---|---|---|
| 0-2 hours | No change visible | No change or subtle nuclear changes |
| 2-12 hours | Faint pallor (TTC stain needed) | Early coagulative necrosis; wavy fibers (stretching of non-contractile dead fibers by viable contracting myocardium) |
| 12-24 hours | Reddish-blue discoloration (congestion, extravasated blood) | Coagulative necrosis; pyknosis of nuclei; myocyte hypereosinophilia |
| 1-3 days | Yellow-tan central pallor with hyperemic border | Neutrophilic infiltration |
| 3-7 days | Rimmed by hyperemic granulation tissue; soft yellow-tan center | Macrophage infiltration; beginning removal of dead cells |
| 1-3 weeks | Pale gray-white, firmer | Granulation tissue; fibroblast proliferation; collagen deposition |
| 6+ weeks | Dense white fibrous scar | Mature fibrous scar |
Key stain: Triphenyl tetrazolium chloride (TTC) - viable myocardium stains brick-red; infarcted area appears as unstained pale zone (dehydrogenases leaked from dead cells).
(Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 512-513)
Types of MI
By Depth
- STEMI (ST-Elevation MI) - Transmural infarction; complete coronary occlusion; full-thickness necrosis through the ventricular wall
- NSTEMI (Non-ST-Elevation MI) - Subendocardial infarction; incomplete occlusion; necrosis confined to inner 1/3 to 1/2 of wall
- UA (Unstable Angina) - Ischemia without biomarker elevation (together with NSTEMI = NSTE-ACS)
Fourth Universal Definition - Types by Mechanism
| Type | Mechanism |
|---|---|
| Type 1 | Atherothrombosis (plaque rupture/erosion) |
| Type 2 | Supply-demand mismatch (e.g., vasospasm, tachyarrhythmia, anemia, hypotension) |
| Type 3 | Cardiac death before biomarker results available |
| Type 4a/b | PCI-related / stent thrombosis |
| Type 5 | CABG-related |
Clinical Features
Symptoms
- Chest pain - severe, crushing, pressure-like or squeezing, classically radiating to the left arm, jaw, neck, or back; typically lasts >20 minutes
- Diaphoresis, nausea, vomiting
- Dyspnea, anxiety, sense of impending doom
- Silent MI - occurs in ~20-25% of patients (especially diabetics and elderly women)
Signs
- Tachycardia, hypertension (early) or hypotension (cardiogenic shock)
- S3 or S4 gallop
- Mitral regurgitation murmur (papillary muscle dysfunction)
- Pericardial friction rub (2-4 days post-MI)
- Jugular venous distension (RV infarct or LV failure)
ECG Changes
The three major ECG abnormalities in acute MI (Ganong's physiology):
| Defect in Infarcted Cells | Current Flow | ECG Change (Leads Over Infarct) |
|---|---|---|
| Rapid repolarization | Out of infarct | ST segment elevation |
| Decreased resting membrane potential | Into infarct | TQ segment depression (appears as ST elevation) |
| Delayed depolarization | Out of infarct | ST segment elevation |
Evolution of ECG Changes
- Hyperacute T waves - tall peaked T waves (earliest change, minutes)
- ST elevation - hallmark of acute STEMI (early hours)
- Q wave formation - appears over days/weeks; indicates transmural necrosis
- T wave inversion - evolves as ST normalizes
- LBBB (new) - equivalent to STEMI
Localization by Leads
| Leads | Territory |
|---|---|
| II, III, aVF | Inferior (RCA) |
| V1-V4 | Anterior (LAD) |
| I, aVL, V5-V6 | Lateral (LCx) |
| V1-V2 (tall R, ST depression) | Posterior (RCA/LCx) |
(Ganong's Review of Medical Physiology, p. 534)
Biomarkers
| Marker | Rises | Peaks | Returns to Normal |
|---|---|---|---|
| Troponin I / T (preferred) | 3-6 hours | 12-24 hours | 7-14 days |
| CK-MB | 4-8 hours | 18-24 hours | 48-72 hours |
| Myoglobin | 1-4 hours | 6-7 hours | 24 hours |
- High-sensitivity troponin (hs-cTn) is the standard of care; enables rapid 0h/1h or 0h/2h rule-in/rule-out algorithms
- Serial troponin measurements are required (rise and/or fall pattern confirms acute injury)
Management
Immediate General Measures (MONA - modified)
- Morphine - for pain (use cautiously; may mask symptoms, possible harm in some)
- Oxygen - only if SpO2 < 90%
- Nitroglycerin - sublingual/IV (avoid in RV infarct, hypotension, PDE5 inhibitor use)
- Aspirin - 325 mg loading dose immediately (antiplatelet)
STEMI Management - Reperfusion (Time-Critical)
"Time is myocardium"
| Strategy | Goal | Indication |
|---|---|---|
| Primary PCI (preferred) | Door-to-balloon <90 min | Available within 120 min of first medical contact |
| Fibrinolysis (tPA, streptokinase) | Door-to-needle <30 min | PCI not available within 120 min; no contraindications |
Antithrombotic Therapy
- Dual antiplatelet therapy (DAPT): Aspirin + P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel in ACS)
- Anticoagulation: UFH, LMWH (enoxaparin), bivalirudin, or fondaparinux during PCI
- Long-term DAPT: Preferably 12 months post-ACS; shorter if high bleeding risk
Key P2Y12 Inhibitors
| Drug | Notes |
|---|---|
| Ticagrelor | Preferred in NSTE-ACS; direct, reversible |
| Prasugrel | More potent; avoid if prior stroke/TIA |
| Clopidogrel | Prodrug; CYP2C19 polymorphism reduces efficacy in some patients |
| Cangrelor | IV, direct, rapidly acting; used peri-PCI |
Long-Term Secondary Prevention
| Drug Class | Indication |
|---|---|
| Beta-blockers | Reduce re-infarction and arrhythmia (especially if EF reduced); recent meta-analysis questions benefit if preserved EF - see PMID 39298680 |
| ACE inhibitors / ARBs | All MI patients, especially reduced EF |
| Statins (high-intensity) | All MI patients regardless of LDL |
| Eplerenone/Spironolactone | EF ≤40% + HF symptoms or diabetes |
(Harrison's Principles of Internal Medicine 22E, p. 2154)
Complications
Early (Hours to Days)
- Arrhythmias - most common cause of early death; VF is the leading cause of sudden death in acute MI; also VT, AF, heart blocks
- Cardiogenic shock - most common cause of in-hospital death; occurs when >40% of LV myocardium is infarcted
- Acute LV failure / Pulmonary edema
- RV failure (RV infarct - hypotension + clear lungs + elevated JVP)
Subacute (Days to Weeks)
- Pericarditis (Dressler's syndrome) - autoimmune, weeks after MI
- Free wall rupture - 3-5 days post-MI; sudden hemopericardium; almost universally fatal without surgery
- Ventricular septal rupture - harsh holosystolic murmur + step-up in O2 from RA to RV
- Papillary muscle rupture - acute mitral regurgitation; flash pulmonary edema
- LV aneurysm - persistent ST elevation; thrombus formation; CHF
Late
- Post-MI remodeling - LV dilation and hypertrophy; evolves to ischemic cardiomyopathy
- Sudden cardiac death (see PMID 39378245 - pooled cohort meta-analysis 2024)
- Mural thrombus - risk of systemic embolization; treat with anticoagulation
Prognosis & Risk Stratification
TIMI and GRACE scores are used to stratify risk and guide treatment intensity.
Prognostic factors:
- Size of infarct (degree of EF reduction)
- Presence of cardiogenic shock
- Time to reperfusion
- Completeness of revascularization
- Age and comorbidities
Recent Evidence (2024-2026)
- Beta-blockers after MI without reduced EF: A 2025 meta-analysis in Eur J Prev Cardiol found that beta-blockers do not clearly reduce mortality in post-MI patients with preserved ejection fraction - this challenges long-standing practice
- Sudden cardiac death post-MI: A 2024 pooled individual participant data meta-analysis in Eur Heart J identified that risk is highest in the first 30 days post-MI and then declines - refining ICD implantation timing decisions
Quick Summary Diagram
Plaque rupture/erosion
↓
Thrombus formation (TXA2, ADP, serotonin, tissue factor)
↓
Coronary artery occlusion
↓
Ischemia → Necrosis (if >20 min)
↓
STEMI (transmural) or NSTEMI (subendocardial)
↓
ECG changes + Troponin rise
↓
Reperfusion (PCI/thrombolysis) + DAPT + Anticoagulation
↓
Secondary prevention (statin, ACEi, beta-blocker)
Sources:
- Robbins, Cotran & Kumar Pathologic Basis of Disease (10th ed.), pp. 510-515
- Robbins & Kumar Basic Pathology (11th ed.), pp. 467-471
- Ganong's Review of Medical Physiology (26th ed.), p. 534
- Harrison's Principles of Internal Medicine (22nd ed., 2025), p. 2154
- Braunwald's Heart Disease (textbook of cardiovascular medicine)
- PMID 39298680 - Beta-blockers post-MI (meta-analysis 2025)
- PMID 39378245 - Sudden cardiac death post-MI (meta-analysis 2024)
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