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Myocardial Infarction

Definition

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Epidemiology

• Frequency rises progressively with age and atherosclerotic 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 have relative protection during reproductive years; menopause accelerates risk
• Overall in-hospital death rate is ~7-8%; STEMI mortality ~10%, NSTEMI ~6%
• Out-of-hospital: one-third of STEMI patients die (usually from arrhythmia within 1 hour)

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Classification (ACS Spectrum)

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Pathogenesis

1. An atheromatous plaque is eroded or 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. Coagulation activation via tissue factor exposure adds to the growing thrombus
4. Within minutes, the enlarging thrombus may completely occlude the coronary lumen

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Myocardial Response to Ischemia

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Patterns of Infarction

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Histological Features of MI Repair

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ECG Changes

• Acute phase: ST segment elevation in leads over the infarct; reciprocal ST depression in opposite leads
• Hyperacute T waves: broad-based, tall, symmetrical T-waves - earliest STEMI finding
• Days to weeks later: Q waves appear (electrically silent scar fails to contribute positivity)
• STEMI = ST elevation in ≥2 contiguous leads (criteria: ≥2 mm in V1-V3; ≥1 mm in other leads)

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Cardiac Biomarkers

• Troponins I and T are not normally in circulation; they are the most sensitive and specific markers
• They remain elevated for 7-10 days, allowing late diagnosis when CK-MB has normalized
• With reperfusion, both peak earlier due to rapid washout
• CK-MB was long the standard but is now largely replaced by troponins

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Reperfusion Injury

1. Mitochondrial dysfunction - altered membrane permeability leads to outer membrane rupture, releasing pro-apoptotic contents
2. Myocyte hypercontracture - intracellular Ca²⁺ overload causes uncontrolled myofibril contraction
3. Free radicals (O₂⁻, H₂O₂, •OH) damage membrane proteins and phospholipids
4. Leukocyte aggregation in reperfused vessels causes "no-reflow" phenomenon

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Clinical Features

• Chest pain: severe, crushing, pressure-like, substernal - often radiates to left arm, jaw, or epigastrium; typically lasts >20 minutes
• Associated: diaphoresis, nausea, dyspnea, syncope
• "Angina equivalents" in certain populations: women, diabetics, and post-op patients may present atypically (dyspnea or fatigue alone)
• Silent MI: can occur in elderly and diabetics without pain

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Treatment

Immediate Management (STEMI)

• ECG within 10 minutes of arrival
• Goal: PCI within 90 minutes (door-to-balloon) or within 120 minutes of first medical contact
• Supplemental O₂ only if SpO₂ <90%

Upstream Medical Therapy

Reperfusion Strategies

• Primary PCI: preferred if door-to-balloon time ≤90 min and PCI-capable facility available; stent placement
• Fibrinolysis (thrombolytics): tPA, reteplase, or tenecteplase - used when PCI not available within 120 minutes; followed by transfer to PCI center
• NSTEMI: generally managed conservatively initially; early invasive strategy for high-risk patients

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Complications

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Key Points Summary

1. MI = coagulative necrosis due to sustained ischemia (>20-40 min), most often from plaque rupture + thrombosis
2. LAD is the most commonly involved artery (40-50% of MIs)
3. Troponin I/T is the biomarker of choice - rises at 2-4 hrs, peaks at 48 hrs, persists 7-10 days
4. Hallmark ECG change = ST elevation in leads overlying infarct
5. Treatment priority is rapid reperfusion: primary PCI (goal ≤90 min door-to-balloon)
6. Aspirin + dual antiplatelet + anticoagulation are the pillars of antithrombotic therapy
7. Complications span from early arrhythmia/shock to late aneurysm/Dressler's syndrome

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Myocardial Infarction - Pathology-Oriented Review

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1. Definition & Cell Death Mechanism

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

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2. Pathogenesis of Coronary Occlusion

1. Plaque disruption - atheromatous plaque is eroded or suddenly ruptured by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic lipid core to blood
2. Platelet activation - platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin, causing further aggregation and vasospasm
3. Coagulation cascade - tissue factor exposure activates coagulation, adding to the thrombus
4. Occlusion - within minutes, the thrombus fully occludes the lumen

Angiography within 4 hours of MI demonstrates coronary thrombosis in nearly 90% of cases; by 12-24 hours (without intervention), only 60% - some thrombi lyse spontaneously.

Non-atherosclerotic causes (~10% of MIs)

• Vasospasm (cocaine, ephedrine, catecholamines)
• Embolism (from left atrial thrombus in AF, infective endocarditis vegetations, prosthetic valves, patent foramen ovale)
• Vasculitis, amyloid deposition, sickle cell disease (intramural arterioles)
• Microfocal infarction from microembolization

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3. Patterns of Infarction

Distribution by Vessel

Types of Infarction

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4. Gross and Microscopic Morphology - Evolution Over Time

Gross Visualization

• Triphenyl tetrazolium chloride (TTC) stain: colors intact myocardium brick-red (dehydrogenases intact); infarcted zone appears pale/unstained because LDH leaks out through damaged membranes. Works on infarcts >3 hours old.
• Old scars appear white and glistening

Complete Morphological Timeline (Table 9.2 / Table 12.5)

Microscopic Histology Images

• Wavy fibers (0.5-4 hr): viable myocardium stretches and buckles non-contractile dead fibers
• Coagulative necrosis with hypereosinophilic cytoplasm and pyknotic nuclei (4-24 hr)
• Neutrophil infiltrate peaking day 1-3, then dying
• Macrophage phagocytosis of debris, days 5-10 (most pronounced)
• Granulation tissue with capillary ingrowth, weeks 1-2
• Dense fibrous scar by 6-8 weeks (indistinguishable in age regardless of whether 8 weeks or 10 years old)

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5. Reperfusion - Morphological Changes

• Contraction band necrosis (CBN): intense eosinophilic transverse bands of hypercontracted sarcomeres across myofibers - caused by calcium influx through damaged sarcolemma, triggering uncontrolled actin-myosin interactions. Without ATP, sarcomeres lock in this agonal tetanic state
• Infarct is typically hemorrhagic (vascular injury and leakiness)
• Corresponds to grossly visible brick-red/dark hemorrhagic zone

Stunned vs. Hibernating Myocardium

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6. Consequences and Complications

Complications - Organized by Timing

Risk Stratification by Infarct Location

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7. Ventricular Remodeling

• Ventricular dilation + increased O2 demand can worsen ischemia
• Shape changes and scar stiffening further reduce cardiac output
• ACE inhibitors reduce these deleterious effects

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Summary: The Pathologist's Approach to MI