---

Myocardial Infarction (MI)

Definition

• Acute myocardial injury (cardiac troponin rise/fall with at least one value above the 99th percentile upper reference limit), AND
• At least one of:
  • Symptoms of myocardial ischemia
  • New ECG changes (ST/T wave changes or new Q waves)
  • Imaging evidence of new loss of viable myocardium or wall motion abnormality
  • Angiographic or autopsy evidence of coronary thrombus
• Rosen's Emergency Medicine, 10th Ed.

---

Epidemiology

• Approximately 800,000 MIs occur per year in the United States - nearly one every 40 seconds
• Causes almost 400,000 deaths annually
• 10% occur in people under 40 years; 45% under 65 years
• The major underlying cause is atherosclerosis
• Male sex increases relative risk through middle age; females are generally protected during reproductive years due to estrogen; postmenopausal women see rapid acceleration of coronary artery disease (CAD) due to decreased estrogen, increased inflammatory markers, cholesterol, and blood pressure
• Post-menopausal hormone replacement therapy has NOT been shown to be protective and may be detrimental (pro-thrombotic effect)
• Robbins, Cotran & Kumar Pathologic Basis of Disease

---

Types of MI (Universal Classification)

• Rosen's Emergency Medicine

---

Pathogenesis

Coronary Arterial Occlusion (Typical Sequence - ~90% of Cases)

1. Atheromatous plaque erosion or rupture - exposes subendothelial collagen and necrotic plaque contents
2. Platelet adhesion, aggregation, and activation - release of thromboxane A2, ADP, serotonin → further aggregation + vasospasm
3. Coagulation cascade activation via tissue factor → growing thrombus
4. Complete occlusion of the coronary artery lumen within minutes
5. When angiography is performed within 4 hours of onset, coronary thrombosis is demonstrated in nearly 90% of cases. At 12-24 hours (without intervention), only 60% still show thrombosis (spontaneous lysis occurs in some)

Non-Atherosclerotic Causes (~10% of cases)

• Vasospasm with or without atherosclerosis (e.g., cocaine, ephedrine)
• Embolism - from left atrial thrombus (in AF), endocarditis vegetations, prosthetic material, or paradoxical embolism via patent foramen ovale
• Uncommon causes: small vessel vasculitis, sickle cell disease, amyloid deposition, coronary artery dissection
• Robbins, Cotran & Kumar Pathologic Basis of Disease

---

Cellular & Biochemical Response

• The first consequence is cessation of aerobic metabolism within seconds, leading to accumulation of lactic acid and depletion of creatine phosphate and ATP
• Only severe ischemia (flow ≤10% of normal) lasting 20-40 minutes leads to irreversible necrosis
• Irreversible necrosis first occurs in the subendocardial zone (most vulnerable - last to receive blood, exposed to highest intramural pressures), then spreads outward as a "wavefront" toward the epicardium
• Sarcolemmal disruption allows intracellular proteins (troponins, CK-MB) to leak into the circulation - the basis for biomarker testing

• Robbins, Cotran & Kumar; Guyton & Hall Textbook of Medical Physiology

---

Patterns of Infarction

Coronary Artery - Territory Correlation

Infarct Patterns

• Transmural infarction - Full wall thickness necrosis; caused by complete, persistent occlusion of an epicardial vessel; associated with ST-elevation MI (STEMI)
• Subendocardial (nontransmural) infarction - Involves inner layers only; caused by transient/partial occlusion or plaque thrombus that lyses before full-thickness necrosis; also seen with global hypotension (circumferential subendocardial infarct); associated with NSTEMI
• Multifocal microinfarction - Pathology of small intramural vessels (microembolization, vasculitis, catecholamine excess)

---

Morphological (Gross & Microscopic) Changes

Gross Changes

Microscopic (Histological) Changes

• Coagulative necrosis with "wavy fibers" at infarct margins (Day 1)
• Neutrophilic infiltrate peaks at 1-3 days
• Macrophage cleanup peaks 3-7 days
• Granulation tissue forms 7-10 days (infarct heals from borders inward)
• Dense collagenous scar complete by ~6 weeks
• Note: Healed scars cannot be dated - an 8-week and a 10-year-old scar look identical

---

Reperfusion Injury

• Contraction band necrosis - pathognomonic of reperfusion injury; irregular dense transverse bands of hypercontracted sarcomeres
• Gross appearance: Hemorrhagic infarct due to vascular leakage in the zone of reperfusion
• Despite this, reperfusion is still highly beneficial - the sooner achieved, the greater the myocardium salvaged

---

ECG Changes (Ganong's Physiology)

• After days-weeks: ST abnormalities subside; dead muscle becomes electrically silent
• Dead area appears negative relative to normal myocardium during systole → pathologic Q waves develop (or R-wave regression in anterior leads)
• Non-Q-wave (NSTEMI) infarcts tend to be less severe but carry high risk of reinfarction

---

Clinical Presentation

Classic Symptoms

• Crushing, heavy, squeezing chest pain - typically substernal, radiating to left arm, jaw, neck, or back
• Pain lasting >20-30 minutes (distinguishes from stable angina)
• Diaphoresis, nausea, vomiting
• Dyspnea, anxiety, sense of impending doom

Atypical / Anginal Equivalent Presentations

• One-third of ED patients with confirmed AMI have NO chest pain on presentation
• Risk factors for atypical presentation: diabetes mellitus, older age (especially >85 years), female sex, nonwhite ethnicity, dementia, prior stroke/CHF
• In patients >85 years, 60-70% present with anginal equivalents, especially dyspnea
• Women: more likely to present with dyspnea, indigestion, weakness, unusual fatigue, cold sweats, anxiety
• Diabetic patients: "silent MI" (medically unrecognized) occurs in ~40% vs. 25% in non-diabetics
• Presentations that can mimic GERD, GI upset, or anxiety should prompt consideration of ACS
• Rosen's Emergency Medicine

---

Biomarkers

• Troponins begin to rise in 2-4 hours, peak at 24-48 hours, remain elevated 7-10 days
• With reperfusion: troponin levels peak earlier and may be higher (rapid washout)
• "Troponin leak" (low-level elevation) is seen in CHF, PE, renal failure, sepsis - serial measurements and clinical context help distinguish
• Robbins, Cotran & Kumar

---

Causes of Death

1. Decreased cardiac output - systolic stretch of non-contracting infarcted muscle further reduces effective pump function; in large infarcts (>40% of LV mass) → cardiogenic shock
2. Pulmonary edema - LV failure → damming of blood in pulmonary vasculature
3. Ventricular fibrillation - most common cause of sudden death early post-MI; due to:
   • Abnormal action potentials at infarct border zone
   • Re-entrant circuits from slowed conduction around infarcted area
   • Ventricular dilation increasing conduction pathway length
4. Cardiac rupture - occurs days 3-10 as necrotic muscle degenerates and thins; free wall rupture → cardiac tamponade → sudden death; septal rupture → VSD; papillary muscle rupture → acute mitral regurgitation
5. Other arrhythmias: complete heart block (especially RCA occlusion affecting AV node), ventricular tachycardia

• Guyton & Hall Textbook of Medical Physiology

---

Complications

---

Treatment

Initial (Acute) Management

• Oxygen - for hypoxia or respiratory distress (target SpO₂ ≥94%)
• Aspirin (antiplatelet) - immediately; inhibits TXA₂-mediated platelet aggregation
• P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) - dual antiplatelet therapy
• Anticoagulation - heparin (UFH or LMWH) or bivalirudin
• Nitroglycerin - for pain relief and preload reduction (avoid in RV infarct, hypotension, phosphodiesterase inhibitor use)
• Beta-blockers - reduce heart rate, oxygen demand; decrease risk of VF; start early if no contraindications (avoid in cardiogenic shock, severe bradycardia)
• Morphine - pain relief; used with caution (may mask symptoms, possible harm in NSTEMI)

Reperfusion (Primary Goal)

• STEMI: Primary percutaneous coronary intervention (PCI) is the gold standard; target door-to-balloon time <90 minutes
  • If PCI not available within 120 minutes: thrombolysis (fibrinolytics: streptokinase, tPA, tenecteplase)
  • Reperfusion is most beneficial when achieved quickly; benefits of early thrombolysis/angioplasty are well established
• NSTEMI/UA: Risk-stratify; early invasive strategy (angiography ± PCI) vs. conservative strategy based on TIMI/GRACE score

Long-term Management

• ACE inhibitors (or ARBs) - reduce remodeling; especially in reduced EF
• Beta-blockers - continued long-term; mortality benefit
• Statins - high-intensity statin therapy regardless of baseline LDL
• Dual antiplatelet therapy (DAPT) - for 12 months post-ACS/stent
• Aldosterone antagonists (eplerenone, spironolactone) - in HFrEF post-MI
• Cardiac rehabilitation - improves outcomes and quality of life
• Robbins, Cotran & Kumar; Guyton & Hall; Rosen's Emergency Medicine

---

Recovery & Healing

• After a large MI, dead fibers in the infarct center enlarge over days
• Marginal collateral channels expand progressively, salvaging peri-infarct zone
• Most nonfunctional muscle around the infarct eventually recovers over days to 3 weeks
• In non-necrotic ischemic zones, pumping power typically returns to near-normal
• The central necrotic area is replaced by fibrous scar tissue (complete by 6-8 weeks)
• The remaining healthy muscle undergoes compensatory hypertrophy to maintain output
• If >40% of LV mass is infarcted, adequate compensatory hypertrophy may be impossible, leading to progressive HF
• Guyton & Hall Textbook of Medical Physiology

---