CLS - Coronary Artery Disease

Question 1

DEVELOPMENT OF ATHEROSCLEROSIS

Answer 1

1. Adaptive Intimal Thickening (Adaptive IT)
   
   • SM cells + proteoglycans accumulate in the intima
2. Intimal xanthoma
   
   • Accumulation of fat
3. Pathological IT (eccentric plaque)
   
   • SM cell + proteoglycan plaque
   • Apoptosis of foam cells (via ER stress pathway)
   • Accumulation of lipids (lipid pool)
   • Microcalcifications
4. Fibrous Cap Atheroma
   
   • Necrotic core
     
     • Early (foam cell apoptosis + clearance by phagocytosis)
     • Late (excessive foam cell apoptosis + defective phagocytosis)
   • No SM cells
   • Lipid pool
   • Cholesterol clefts
   • Foam cells present
5. Thin-Cap Fibroatheroma (TCFA) = Vulnerable Plaque
   
   • Focal manifestation of a systemic disease
   • Thin fibrous cap (< 65um)
   • Large necrotic core
   • Cap infiltrated by macrophages and lymphocytes
   • Cap composition:
     
     • Type I collagen
     • Few or no SM cells
6. Plaque rupture
7. Lesion progression/thrombosis
   
   • Failure of EPCs to heal endothelial rupture
     
     • Incompetent bone marrow
   • Macrophage phagocytosis and inflammation
   • Vascularization (development of new vasa vasorum)
8. Plaque rupture
   
   • Healing –> Quiescent state (Asymptomatic)
   • Plaque Thrombosis (Symptomatic)
     
     • Acute Coronary Syndrome
   • Accelerated Plaque Progression
     
     • Symptomatic OR asymptomatic

Question 2

POTENTIALLY HEALED PLAQUES

Answer 2

• IT –> Macrophages –> fatty streak
  
  • Phagocytosis of early necrotic core
  • Potential regression of atherosclerosis
• FCA –> Vessels can compensate with positive remodeling
  
  • Grow in diameter to maintain lumen size
  • Continuous plaque growth = expansion is overcome
    
    • Lumen narrows

Question 3

IMAGING OF VESSELS

Answer 3

• IVUS (intravascular ultrasound)
  
  • Determine lumen size
• IVUS-VH (virtual history)
  
  • Determine plaque size, density, and composition
  • Better, because lumen size not indicative of vascular health

Question 4

ATHEROSCLEROSIS/VULNERABLE PLAQUE

Answer 4

• PIT = most accepted lesion precursors of complex fibroatheroma formation
• TCFA = bulky, acellular, proximal segments of coronary vessels
• Plaque biomechanics –> role in disruption of fibrous cap –> plaque rupture
  
  • Plaque healing after a “silent rupture” = most likely mechanism of plaque progression and stenosis
• TCFA = most common type of VP
• Any atherosclerotic plaque is technically vulnerable to causing coronary thrombosis in the right environment

Question 5

CLINICAL MANIFESTATIONS OF CAD

Answer 5

• Stable CAD = Stable Angina
  
  • Severe narrowing of artery –> periodic ischemia
  • Inducible (reversible) chest pain on exertion/big meals
    
    • Stress test!
  • No infarcts
  • Treatment
    
    • Elective PCI (percutaneous coronary intervention)
    • Coronary bypass surgery
    • Optimal medical therapy (drugs + exercise & diet)
• Unstable CAD = ACS
  
  • Thrombus
  • Sudden partial or complete coronary occlusion
  • Severe, constant pain
  • Imminent/sustained infarct
  • Heart failure