Myocardial Infarction - Overview

Definition

• ~800,000 MIs occur in the United States per year (nearly one every 40 seconds)
• ~400,000 deaths annually
• 10% occur before age 40; 45% before age 65
• Men are at higher risk than women, but the gap narrows with age; post-menopausal women lose estrogen-mediated protection, making IHD the #1 cause of death in older women

Types of MI

By Depth of Necrosis

By Clinical/ECG Presentation

Universal Classification (Types 1-5)

• Type 1 - Spontaneous MI from plaque rupture/erosion with thrombosis (classic atherothrombotic)
• Type 2 - Supply-demand mismatch (tachyarrhythmia, anemia, hypotension, vasospasm) without plaque rupture
• Type 3 - Sudden cardiac death before biomarkers can be drawn
• Type 4a/4b - MI associated with PCI or stent thrombosis
• Type 5 - MI associated with CABG

Pathophysiology

Step 1: Coronary Artery Occlusion

1. An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces - exposing subendothelial collagen and necrotic plaque contents to circulating blood
2. Platelets adhere, aggregate, and are activated - releasing thromboxane A2, ADP, and serotonin, causing further platelet aggregation and vasospasm
3. Activation of coagulation via tissue factor exposure adds to the growing thrombus
4. Within minutes, the thrombus can completely occlude the coronary artery lumen

Evidence: Angiography within 4 hours of MI onset shows coronary thrombosis in ~90% of cases. By 12-24 hours, this falls to ~60% - indicating that some occlusions clear spontaneously via thrombolysis or spasm relaxation.

• Vasospasm (with/without atherosclerosis) - cocaine, ephedrine
• Embolism (from atrial fibrillation mural thrombus, endocarditis vegetations, prosthetic material, or patent foramen ovale)
• Small vessel disorders: vasculitis, sickle cell disease, amyloid deposition, vascular dissection

Fig. Progression of myocardial necrosis - Robbins & Cotran Pathologic Basis of Disease

Step 2: Myocardial Response to Ischemia

• Cessation of aerobic metabolism → inadequate ATP production → accumulation of lactic acid
• Loss of contractility within minutes (before cell death - this is reversible)
• Sarcolemmal membrane disruption allows intracellular proteins (troponin, CK-MB) to leak into circulation - basis of biomarker testing
• Only ischemia of 20-40 minutes or longer (with blood flow ≤10% of normal) leads to irreversible necrosis

The "Wavefront Phenomenon"

• It is the last area to receive blood from epicardial vessels
• Exposed to the highest intramural pressures, impeding blood inflow

Step 3: Vascular Territory and Location

Morphological Progression (Gross & Microscopic)

MIs < 12 hours old are often not visible on gross examination. The triphenyl tetrazolium chloride (TTC) stain reveals early infarcts: viable myocardium stains brick-red; infarcted (enzyme-depleted) tissue appears as an unstained pale zone.

Reperfusion Injury

• Stunned myocardium - reperfused myocardium may be profoundly non-contractile for days despite viability (persistent biochemical abnormalities)
• Reperfusion injury - reactive oxygen species and calcium overload cause additional damage at the moment of reperfusion
• Arrhythmias - ischemic regions show electrical instability; in 80-90% of cases, cardiac death in MI is due to ventricular fibrillation (not mechanical failure)

Summary

Myocardial Infarction - Overview, Types & Pathophysiology

Definition

• ~800,000 MIs per year in the United States (one every ~40 seconds)
• ~400,000 deaths annually
• 10% occur before age 40; 45% before age 65
• Men at higher risk than women until menopause, after which the gap closes - IHD is the #1 cause of death in older women

Types of MI

By Depth of Necrosis

By ECG / Clinical Presentation

Universal Classification (Types 1-5)

Pathophysiology

1. Coronary Artery Occlusion (Typical Type 1 Sequence)

1. An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces - exposing subendothelial collagen and necrotic plaque contents to blood
2. Platelets adhere, aggregate, and activate - releasing thromboxane A₂, ADP, and serotonin, driving further aggregation and vasospasm
3. Coagulation cascade activation via tissue factor exposure amplifies the growing thrombus
4. Within minutes, the thrombus can completely occlude the coronary lumen

Angiography within 4 hours of MI onset shows thrombotic occlusion in ~90% of cases. By 12-24 hours this falls to ~60%, as some occlusions clear spontaneously through lysis or spasm relaxation - the basis for thrombolytic therapy.

• Vasospasm (cocaine, ephedrine, or idiopathic)
• Embolism (from atrial fibrillation mural thrombus, endocarditis vegetations, prosthetic material, patent foramen ovale)
• Small vessel disease: vasculitis, sickle cell disease, amyloid deposition, vascular dissection
• Severe fixed atherosclerosis + increased demand (tachycardia, hypertension) - causes subendocardial infarction without frank thrombosis

2. Cellular Response to Ischemia

• Cessation of aerobic metabolism → ATP fails → lactic acid accumulates
• Loss of myocardial contractility within 1-2 minutes (reversible at this stage)
• Sarcolemmal membrane disruption → intracellular proteins (troponin, CK-MB) leak into interstitium and circulation - the basis of biomarker testing
• Only ischemia lasting ≥20-40 minutes with blood flow ≤10% of normal produces irreversible coagulative necrosis

3. The "Wavefront Phenomenon" - How Necrosis Spreads

• Last region to receive blood delivered via epicardial vessels
• Exposed to the highest intramural pressures, impeding blood inflow

Progression of myocardial necrosis after coronary artery occlusion (Robbins & Cotran Pathologic Basis of Disease)

Clinical implication: This wavefront is why "time is muscle" - early reperfusion (PCI or thrombolysis) interrupts the wavefront and limits infarct size.

4. Coronary Territory and Infarct Location

• Left main coronary artery occlusion is rare but catastrophic
• 15-30% of RCA occlusions extend into the right ventricular wall
• Isolated RV infarction is unusual (1-3% of cases)

Morphological Progression

MIs < 12 hours old are often invisible on gross examination. The triphenyl tetrazolium chloride (TTC) stain is used to detect early infarcts: viable myocardium stains brick-red (preserved dehydrogenase activity); infarcted tissue appears as an unstained pale zone (enzymes have leaked out).

Reperfusion and Its Consequences

• Stunned myocardium - viable but non-contractile for days after reperfusion, due to persistent biochemical dysfunction; may produce transient but reversible cardiac failure
• Reperfusion injury - reactive oxygen species and calcium overload at the moment of reperfusion cause additional myocyte death
• Arrhythmias - ischemic regions develop electrical instability; in 80-90% of cases, cardiac death in MI is from ventricular fibrillation, not mechanical failure
• No-reflow phenomenon - microvascular injury after >1 hour of ischemia can prevent tissue reperfusion even after the epicardial vessel is opened

Key Takeaways

1. MI = irreversible ischemic necrosis of cardiomyocytes, threshold at 20-40 minutes of severe ischemia
2. The dominant mechanism is plaque rupture → platelet aggregation → thrombus → occlusion
3. Necrosis spreads as a subendocardial-to-epicardial wavefront over 6-12 hours
4. Three anatomical patterns: transmural (STEMI), subendocardial (NSTEMI), microinfarction
5. Five universal types by mechanism (Type 1-5), with Type 1 atherothrombotic being the most common
6. Biomarker release (troponin, CK-MB) reflects sarcolemmal disruption and is the clinical cornerstone of diagnosis