Pathophysiology of Coronary Artery Disease

Question 1

Right Coronary Artery

• Origin
• In 90% of people
• In 10% of people
• Right coronary artery

Answer 1

• Origin
  
  • Right coronary ostium –> right in the AV groove
• In 90% of people
  
  • –> right dominant artery –> posterior descending artery –> posterior interventricular septum
  • Dominant right coronary artery –> AV nodal artery
• In 10% of people
  
  • –> left dominant artery –> circumflex artery –> posterior descending artery
  • Dominant circumflex artery –> AV nodal artery
• Right coronary artery
  
  • –> branches –> anterior right ventricular wall
  • –> acute marginal branch –> free margin of the RV
  • –> posterolateral branches distal to the posterior descending artery

Question 2

Left Coronary Artery

Answer 2

• Origin: left coronary ostium
• –> left main coronary artery
  
  • –> left anterior descending (LAD) coronary artery
    
    • –> anterior interventricular groove overlying the septum
    • –> diagonal vessels that traverse the anterolateral wall
    • –> septal perforator vessels that penetrate the interventricualr septum
  • –> circumflex artery
    
    • –> AV groove to the left
    • –> obtuse marginal vessels
  • –> ramus artery at the bifurcation of the LAD & circumflex artery

Question 3

Coronary Artery Disease

• Coronary atherosclerosis
• Atherosclerotic lesions in a coronary artery
  
  • Two types
  • Differences
• Angiography
• Techniques that can image the vessel wall & provide additional info regarding total disease burden

Answer 3

• Coronary atherosclerosis
  
  • Frequently diffuse down vessel wall w/ segmental areas of more severe obstruction
  • Frequently eccentric in vessel wall
• Atherosclerotic lesions in a coronary artery
  
  • Two types
    
    • Circumferential (sometimes)
    • Eccentric (often)
  • Differences
    
    • Vulnerability to vasospasm at the site of the lesion
    • Respond differently to interventional procedures
• Angiography
  
  • Silhouette technique to visualize the lumen
  • Gives info about the degree of obstruction of the vessel lumen
  • Limited ability to quantify the extent of the disease b/c the atherosclerotic burden is intramural
• Techniques that can image the vessel wall & provide additional info regarding total disease burden
  
  • Intracoronary ultrasound
    Cardiac CT imaging
  • Cardiac MRI

Question 4

Cardiovascular Disease and Mortality

Answer 4

• CV disease: largest cause of mortality in th eUS
• Equal frequency in men & women
• Occurs 10 years later in women during post-menopause

Question 5

Of asymptomatic men 30-60yo, 5% per year will develop symptomatic CAD manifested by…

Answer 5

• Myocardial infarction
• Stable angina pectoris
• Sudden death
• Unstable angina pectoris

Question 6

Oxygen Requirements of the Heart

Answer 6

• Heart: obligate aerobic organ
  
  • To do more work, it has to consume more oxygen
• It has a limited capacity to generate energy through anaerobic metabolism
• Oxygen requirements of the heart are 5x greater than the rest of the body
  
  • LV: particularly oxygen demanding, 20x greater than the rest of the body

Question 7

Oxygen Consumption

• Total amount of oxygen delivered to an organ is a product of…
• Normal arterial blood
• Oxygen consumption of an organ is a product of…
• Arteriovenous oxygen difference (AVO2 difference)

Answer 7

• Total amount of oxygen delivered to an organ is a product of…
  
  • Oxygen carrying capacity of the blood
    
    • Determined by the hemoglobin concentration in the RBCs
  • Total blood flow
• Normal arterial blood
  
  • Fully saturated w/ oxygen
• Oxygen consumption of an organ is a product of…
  
  • Blood flow to the organ
  • Extraction of oxygen from the blood that perfuses it
• Arteriovenous oxygen difference (AVO2 difference)
  
  • Extraction of oxygen from the blood as it passes through an organ
  • Systemic AVO2 difference (total body oxygen extraction) = (oxygen content of the systemic arterial blood) - (oxygen content of blood returning to the pulmonary artery)

Question 8

Oxygen Extraction

• Blood returning to the pulmonary artery to be re-oxygenated
  
  • Rest
  • Exercise
• Blood in the coronary sinus (venous drainage of coronary circulation)
  
  • Rest
  • Exercise

Answer 8

• Blood returning to the pulmonary artery to be re-oxygenated
  
  • Rest: 70% saturated w/ oxygen
  • Exercise: increase total oxygen consumption by extracting more oxygen from blood it’s already receiving
• Blood in the coronary sinus (venous drainage of coronary circulation)
  
  • Rest: 30% satured w/ oxygen
  • Exercise: little capacity to increase its oxygen consumption by increasing oxygen extraction
• Only way the heart can increase its oxygen consumption
  
  • Increase oxygen delivery (perfusion)
    
    • B/c areriovenous oxygen difference in the heart is nearly max at rest
    • Heart can’t control hemoglobin concentration to increase oxygen delivery
  • Explains why coronary blood flow is so essnetial to myocardial performance
  • Explains why CAD limiting this flow has such severe implications

Question 9

Coronary Blood Flow

• Autoregulation
• Primary determinants of myocardial oxygen demand (& coronary blood flow)
• Congestive heart failure & digoxin

Answer 9

• Autoregulation
  
  • Demand of heart for oxygen is kept in balance w/ supply of oxygen to the heart
• Primary determinants of myocardial oxygen demand (& coronary blood flow)
  
  • HR
    
    • Greatest determinant
    • Increase HR –> increase myocardial oxygen demand
  • Systolic BP
    
    • Determines wall tension & myocardial oxygen demand
    • More expensive to the heart in terms of myocardial oxygen demand
    • Hypertension or aortic stenosis –> increase pressure in ventricle –> greater oxygen requirement than increased volume
  • LV volume/radius (LaPlace relationship)
    
    • Determines wall tension & myocardial oxygen demand
    • Less expensive to the heart in terms of myocardial oxygen demand
    • Aortic or mitral regurgitation –> increase volume in ventricle –> less oxygen requirement than increased pressure
  • Contractility
    
    • Increase contractility –> increase myocardial oxygen demand
• Congestive heart failure & digoxin
  
  • Increase HR, BP, & volume –> increase myocardial oxygen demand
  • Digoxin: increase contractility –> resolve congestive heart failure –> decrease HR, BP, & volume –> decrease myocardial oxygen consumption

Question 10

Perfusion Pressure

• Coronary perfusion pressure
• LV systolic pressure vs. aortic systolic pressure

Answer 10

• Coronary perfusion pressure
  
  • Difference b/n aortic pressure & pressure in coronary sinus (venous drainage of coronary circulation)
• LV systolic pressure vs. aortic systolic pressure
  
  • Since LV systolic pressure = aortic systolic pressure, there’s no pressure gradient to drive coronary blood flow through the LV myocardium in systole
  • In the LV, coronary blood flow is limited to diastole
  • Aortic diastolic pressure primarily drives pressure for coronary perfusion

Question 11

Systolic Coronary Blood Flow

Answer 11

• Blood flow in the LV during systole
  
  • When flow is limited to systole, transmyocardial flow in teh LV drops
  • Flow is preserved to the epicardial vessels for capacitance
    
    • Flow doesn’t proceed through the myocardial wall
  • Systolic LV pressure = central aortic pressure
    
    • –> no pressure gradient to drive coronary flow through the LV
  • ► coronary blood flow in the LV is primarily a diastolic phenomenon
  • ► perfusion to the endocardium is exclusively diastolic
• Blood flow in the RV during systole
  
  • RV systolic pressure is lower than systemic arterial pressure
    
    • –> pressure gradient during systole to drive coronary perfusion to the RV

Question 12

Resistance to Coronary Perfusion

• R1 vessels: epicardial coronary arteries & larger intramyocardial vessels
• R3: vessels contained within myocardium
• R2: smaller arteries & precapillary arterioles
• R2 + R3
• High R3 component in systole in the LV
• Lower R3 component in epicardial regions

Answer 12

• R1 vessels: epicardial coronary arteries & larger intramyocardial vessels
  
  • Vessels seen on a coronary angiogram
  • Contribute little to resistance to coronary perfusion
  • Primarily serve a capacitance function
• R3: vessels contained within myocardium
  
  • Coronary arteries penetrate from epicardium –> myocardium –> endocardium
  • Any force exerted against the myocardium is unevenly distributed across the myocardial wall
    
    • Greatest in the subendocardium
    • Least in the subepicardium
• R2: smaller arteries & precapillary arterioles
  
  • Contribute more to coronary perfusion
  • Vasodilate in the subendocardial region –> decrease R2 resistance –> overcome R3 resistance & protect subendocardial perfusion
• R2 + R3
  
  • Kept constant to preserve subendocardial perfusion
• High R3 component in systole in the LV
  
  • Systolic wall tension
  • Limits perfusion of the LV to diastole
• Lower R3 component in epicardial regions
  
  • Why some systolic perfusion to that region can still occur
  • Blood can’t flow into distal vasculature in systole, but its capacitance can flow
  • Fills epicardial vessles w/ blood that then perfuses distally during diastole

Question 13

Coronary Vascular Resistance vs. Pressure

• R1 vessels: epicardial & larger intramyocardial vessels
• R2 vessels: prearteriolar & arteriolar vessels

Answer 13

• R1 vessels: epicardial & larger intramyocardial vessels
  
  • Contribute little to resistance to coronary blood flow
  • Serve primarily a capacitance function
  • Decrease in pressure as blood flows through them is minor
• R2 vessels: prearteriolar & arteriolar vessels
  
  • Where greatest decrease in pressure occurs as blood flows through the arterial bed to the venous circulation

Question 14

Autoregulation of Coronary Blood Flow

• Autoregulatory range of perfusion
• As perfusion pressure drops below a critical level…
• If perfusoin pressure increases to very high levels…

Answer 14

• Autoregulatory range of perfusion
  
  • Rest: coronary blood flow is maintained at a constant level through this wide range of coronary perfusion pressures (circled)
• As perfusion pressure drops below a critical level…
  
  • Coronary perfusion can’t be futher protected
  • Coronary blood flow decreases proportionally to decreasing perfusion pressure (solid arrow)
  • Occurs when the R2 resistance vessels have maximally vasodilated
• If perfusoin pressure increases to very high levels…
  
  • It overwhelms the resistance vessels’ ability to regulate it
  • Coronary blood flow increases proportionally to increasing perfusion pressure (open arrow)

Question 15

Determinants of Myocardial Oxygen Demand at Rest & During Exercise

• At exercise
  
  • Myocardial oxygen demand & coronary blood flow
  • HR
  • Systolic BP
  • LV volume
  • Contractility
• Double product

Answer 15

• At max exercise
  
  • Myocardial oxygen demand & coronary blood flow increase
  • HR increases –> coronary blood flow increases (most important determinant)
  • Systolic BP increases –> myocardial demand increases
  • LV volume may or may not increase depending on the type of exercise & the position
  • Contractility increases by direct rate related effects (Treppe effect) & by an increase in circulating catecholamines
• Double product
  
  • Product of HR & systolic BP
  • Correlates closely w/ coronary blood flow

Question 16

Autoregulation of Coronary Blood Flow

• Myocardial oxygen demand vs. myocardial oxygen supply
• Myocardial oxygen extraction in the coronary circulation at rest

Answer 16

• Myocardial oxygen demand vs. myocardial oxygen supply
  
  • Increase mycoardial oxygen demand –> increase myocardial oxygen supply in a linear fashion
  • Controlled by the autoregulation of coronary blood flow
• Myocardial oxygen extraction in the coronary circulation at rest
  
  • Myocardial oxygen extration is nearly maximal
  • Heart can’t increase its oxygen consumption by increasing oxygen extraction from the blood it’s already receiving
  • Increase oxygen demand –> increase coronary blood flow –> increase myocardial oxygen supply

Question 17

Myocardial Oxygen Supply During Exercise

• Systolic vs. diastolic BP during exercise
• Increasing coronary blood flow
• As HR increases during exercise…
• Net effect

Answer 17

• Systolic vs. diastolic BP during exercise
  
  • Systolic BP primarily increases
  • Diastolic BP shouldn’t increase
• Increasing coronary blood flow
  
  • R2 vessels vasodilate –> R2 vessels decrease their resistance –> increase coronary blood flow
• As HR increases during exercise…
  
  • Diastole shortens –> coronary perfusion time shortens
• Net effect
  
  • Decreased R2 resistance + shortened diastolic time interval –> increase coronary blood flow during max exercise

Question 18

Autoregulation of Coronary Blood Flow

• R2 vasodilation vs. coronary blood flow
• Coronary flow reserve
• Max coronary blood flow & coronary vasodilator reserve

Answer 18

• R2 vasodilation vs. coronary blood flow
  
  • Increase vasodilation of R2 vessels –> increase coronary perfusion pressure –> increase max coronary blood flow
• Coronary flow reserve
  
  • Difference b/n resting & max coronary blood flow
  • Directly dependent on coronary perfusion pressure
• Max coronary blood flow & coronary vasodilator reserve
  
  • 2 different indices that are both directly related to coronary perfusion pressure

Question 19

Myocardial Oxygen Supply: Coronary Artery Disease

• Atherosclerotic coronary artery disease
• Compensation for increased resistance to flow in the R1 vessel
• Remaining ischemia
• Overall compensations

Answer 19

• Atherosclerotic coronary artery disease
  
  • Primarily a disease of the R1 (epicardial & large intramyocardial coronary) vessels
  • CAD –> resistance to flow through the stenotic lesion –> increased R1 resistance
  • Creates a perfusion pressure gradient to flow through the luminal narrowing
• Compensation for increased resistance to flow in the R1 vessel
  
  • Dilate distal R2 vessels –> decreased R2 resistance –> maintain total resistance to perfusion –> preserve flow
• Remaining ischemia
  
  • Some ischemia may remain in the most vulnerable subendocardial region
  • Early manifestation: diastolic dysfunction (shift of pressure/volume curve up & to the left)
  • Result: localized diastolic dysfunciton in R1 (epicardial) vessels –> increase LVEDP –> increase R3 (subendocardial) resistance
• Overall compensations
  
  • Increased R1 resistance –> decrease R1 resistance
  • Increased R3 (subendocardial) resistance –> stenosis in R2 vessels –> R2 (subendocardial) vasodilation –> preserve flow

Question 20

Coronary Blood Flow in CAD

• CAD coronary blood flow: rest
• CAD coronary blood flow: exercise
• In the presence of coronary stenosis…
• As the ventricle becomes ischemic…

Answer 20

• CAD coronary blood flow: rest
  
  • Preserved via autoregulation despite obstructions
  • Primarily preserved via vasodilated R2 vessels
• CAD coronary blood flow: exercise
  
  • R2 dilate –> decrease resistance to flow –> increase coronary blood flow
• In the presence of coronary stenosis…
  
  • R2 vessels have already vasodilated maximally to preserve perfusion at rest
  • There’s nothing more coronary circulation can do to increase perfusion
  • Increase demand + flow can’t increase –> supply/demand mismatch –> ischemia
• As the ventricle becomes ischemic…
  
  • Systolic & diastolic functions deteriorate
  • LVEDP & LVEDV incrase –> increaes R3 resistance –> increase ischemia

Question 21

Autoregulation of Coronary Blood Flow

• Myocardial oxygen demand vs. myocardial oxygen supply
• In the presence of coronary artery obstruction…
• Ischemic area
• Ischemic threshold
• Ischemic threshold for mild coronary disease vs. severe obstructive disease

Answer 21

• Myocardial oxygen demand vs. myocardial oxygen supply
  
  • Increase myocardial oxygen demand –> increase myocardial oxygen supply linearly
• In the presence of coronary artery obstruction…
  
  • Myocardial oxygen supply increases linearly to increase myocardial oxygen demand
  • When R2 vessels vasodilate maximally, coronary circulation autoregulatory reserve is expended
  • Further increases in myocardial oxygen demand don’t further increase mycoardial oxygen supply
• Ischemic area
  
  • Difference b/n normal & coronary artery obstruction curves
  • Supply < demand
• Ischemic threshold
  
  • Point at which the two curves digress
  • Point of max R2 vessel vasodilation
  • Measure of severity of obstructive disease
• Ischemic threshold for mild coronary disease vs. severe obstructive disease
  
  • Mild: ischemic threshold occurs at high levels of myocardial oxygen demand
  • Severe: ischemic threshold occurs at a lower level of demand

Question 22

Autoregulation of Coronary Blood Flow vs. Stenosis

Answer 22

• Max coronary blood flow in coronary artery stenosis decreases relative to coronary perfusion pressure
• Curve S1: mild stenosis
• Curve S2: severe stenosis

Question 23

Coronary Blood Flow Relative to % Stenosis, Rest, & Peak Exercise

• Coronary blood flow at rest
• Coronary blood flow during max exercise
  
  • Stenosis < 50%
  • Stenosis > 50%
    
    • Critical zone
• Stenosis length vs. flow

Answer 23

• Coronary blood flow at rest
  
  • Remains normal w/ obstructions up to 80-90% in severity
  • Reflection of the vasodilatory reserve of R2 vessels
• Coronary blood flow during max exercise
  
  • Stenosis < 50%: peak coronary blood flow is maintained at normal levels
  • Stenosis < 50%: sharp decline in peak coronary blood flow w/ increasing obstructions
    
    • Critical zone: small increase in obstruction –> large decrease in blood flow
• Stenosis length vs. flow
  
  • Increase length of vessel –> decrease peak flow

Question 24

Percent Stenosis Limitations

• Reproducibility
• Diffusibility
• Techniques that can image both the lumen & vessel wall

Answer 24

• Reproducibility
  
  • Percent stenosis is assessed by coronary angiography (visual analysis)
  • Variability in interpretations by coronary angiographers
• Diffusibility
  
  • CAD is often diffuse down the length of a vessel
  • Assess percent stenosis
    
    • Estimate lumen at site of stenosis & compare it to another portion of the lumen of the same vessel that appears normal
    • –> difference estimates percent stenosis
  • If disease is diffuse, area that appears normal may be stenosed
    
    • –> underestimates the true original lumen size & underestimates the severity of the lesion
• Techniques that can image both the lumen & vessel wall
  
  • Intracoronary angiography
  • Cardiac CT & MRI

Question 25

Predicting Flow

• Visual interpretation of coronary angiogram prediction of flow
• Percent stenosis prediction of flow
• Minimal luminal cross sectional area prediction of flow

Answer 25

• Visual interpretation of coronary angiogram prediction of flow
  
  • Poor correlation: visual interpretation underestimates disease severity
• Percent stenosis prediction of flow
  
  • Poor correlation b/n peak flow velocity by doppler measurement & percent diameter / luminal narrowing
  • Percent stenosis, while a widely used standard for assessing disease severity, is actually a crude measurement w/ limitation
• Minimal luminal cross sectional area prediction of flow
  
  • Close correlation b/n peak lumenal area & peak doppler flow
  • Size of remaining lumen matters more than the percent stenosis of the lesion
  • Small vessel w/ 50% stenosis will have a lower peak flow than a large vessel w/ 50% stenosis

Question 26

Endocardium

• Subendocardium
• Myocardial oxygen demand in subendocardium vs. middle & epicardial layers
• R3 component of resistance
• Oxygen demand in the endocardium

Answer 26

• Subendocardium
  
  • Area of myocardium at greatest vulnerability for ischemia
• Myocardial oxygen demand in subendocardium vs. middle & epicardial layers
  
  • Subendcardium > middle or epicardial layers
• R3 component of resistance
  
  • Greatest in the subendocardial region
  • Unevenly distributed across the myocardial wall
  • Increased subendocardial oxygen demand requires increased subendocardial blood flow to meet that demand
• Oxygen demand in the endocardium
  
  • Since pressure is a determinant of myocardial oxygen demand, the increased forces exerted against the endocardial wall increase the oxygen requirements in that area
  • Since oxygen demand is greatest in the endocardial region, the endocardium requires more blood flow at rest than the epicardium to meet that incrased demand

Question 27

Systolic Coronary Blood Flow

• Systolic vs. diastolic persuion in the epicardium & endocardium
• Rate of flow in epicardium vs. endocardium
• Mechanisms by which endocardium receives flow

Answer 27

• Systolic vs. diastolic persuion in the epicardium & endocardium
  
  • Coronary perfusion in the LV is primarily diastolic
  • Epicardium: receives more flow/perfusion in systole
  • Endocardium: receives more flow/perfusion in diastole
• Rate of flow in epicardium vs. endocardium
  
  • Endocardium receives more flow in less time than epicardium
  • Rate of flow in endocardium > epicardium
• Mechanisms by which endocardium receives greater rate of flow
  
  • More vessels per unit area
  • Increased size of the vascular bed
  • R2 vasodilation –> decreased R2 component of resistance at rest

Question 28

Subendocardial Perfusion

• R2 during exercise
• Coronary blood flow vs. HR
• Subendocardial vs. epicardial blood flow at rest
• Subendocardial blood flow in CAD

Answer 28

• R2 during exercise
  
  • R2 vasodilates –> decreases resistance –> provides increased rate of flow to the endocardium
  • Less vasodilating reserve for recruitment int he endocardial region –> makes endocardium more vulnerable to ischemia in the presence of CAD
  • Pts present w/ subendocardial ischemia or infarction
• Coronary blood flow vs. HR
  
  • Increase HR –> increase coronary blood flow –> maintain epicardial blood flow at a consistent level
• Subendocardial vs. epicardial blood flow at rest
  
  • Subendocardial > epicardial blood flow at rest
  • Increase HR –> decrease subendocardial blood flow
• Subendocardial blood flow in CAD
  
  • CAD: subendocardial blood flow is lower than normal at rest & decreases more rapidly than normal as HR increases
  • Peak HR is limited by ischemia