Pathophysiology of Coronary Artery Disease

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Pathophysiology of Coronary Artery Disease

• William P. Follansbee, M.D.

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Right Coronary Artery
Illustration by Frank Netter, Ciba
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Left Coronary Artery
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Coronary Artery Disease

• Coronary atherosclerosis
• Frequently diffuse down vessel wall with
  segmental areas of more severe obstruction
• Frequently eccentric in vessel wall

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41 of all deaths are due to cardiovascular causes
12,400,00 Americans have history of MI or
angina 1,100,000 Americans per year have a
myocardial infarction, of which 40 are fatal
Cost 2001 298.2 billion
From National Center for Health Statistics and
the American Heart Association
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US Mortality Data 1988-1991
National Center for Health Statistics, 1995
From Heller and Fosati, in Zaret and Beller,
editors Nuclear Cardiology, State of the Art and
Future Directions Mosby, 1999.
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Coronary Artery Bypass Surgery
The fastest way to a man's heart is through his
chest. - Roseanne Barr
553,000 Coronary Artery Bypass Procedures
Performed in 1977
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Presenting Manifestation of CAD

• Of asymptomatic men age 30-60, 5 per year will
  develop symptomatic CAD, manifested by
• Myocardial infarction 45
• Sudden death 11
• Stable angina pectoris 32
• Unstable angina pectoris 9

Franmingham Study, American Journal of
Cardiology, 1976
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Coronary Artery Disease Risk Factors
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Myocardial Oxygen Consumption
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Relative Oxygen Requirements Per Gram of Tissue
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Oxygen Consumption

• Oxygen Extraction
• Arteriovenous oxygen difference (AV02 difference)
• Oxygen Delivery
• Oxygen carrying capacity
• Oxygen saturation
• Perfusion

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Oxygen Extraction
Rest
Exercise
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Oxygen Consumption

• Oxygen Extraction
• Arteriovenous oxygen difference (AV02 difference)
• Oxygen Delivery
• Oxygen carrying capacity
• Oxygen saturation
• Perfusion

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Autoregulation of Coronary Blood Flow
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Determinants of Myocardial Oxygen Demand
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Myocardial Oxygen SupplyPerfusion Pressure and
Resistance
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Systolic Coronary Blood Flow
Left Ventricle
Right Ventricle
Adapted fromHess DS and Bache RJ, Circ Research
4588, 1979
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Myocardial Oxygen SupplyPerfusion Pressure and
Resistance
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Determinants of Myocardial Oxygen Demand At Rest
and During Exercise
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Autoregulation of Coronary Blood Flow
Myocardial oxygen supply
Myocardial oxygen demand
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Myocardial Oxygen SupplyExercise
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Myocardial Oxygen SupplyCoronary Artery Disease
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Myocardial Oxygen SupplyCAD During Exercise
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Autoregulation of Coronary Blood Flow
Myocardial oxygen supply
Myocardial oxygen demand
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Autoregulation of Coronary Blood Flow
Normal
Myocardial oxygen supply
Supply lt Demand
Ischemic threshold
CAD
Myocardial oxygen demand
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Coronary Blood Flow Relative to Stenosis, Rest
and Peak Exercise

• At rest, coronary blood flow remains normal with
  obstructions of up to 80-90 in severity.
• During maximal exercise, peak coronary blood flow
  decreases with obstructions of 50 or more in
  severity.
• There is a sharp decline in peak coronary blood
  flow with increasing obstructions beyond 50

Gould KL, Lipscomb K, and Hamilton GW American J
Cardiology 3387, 1974
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Coronary Blood Flow vs Percent Obstruction
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Reproducibility of Assessment of Percent Diameter
Stenosis
Left Main
Proximal LAD
Two experienced blinded (not blind) observers
from different institutions interpreting the same
coronary angiograms
Fisher LD et al, Cathet Cardiovasc Diagn 8565,
1982. As adapted by Marcus ML et al, Progress in
Cardiovascular Diseases 3139, 1988.
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Percent StenosisSegmental vs Diffuse Disease
Harrison DG, White CW, Hiratzka LF et al
Circulation 691111, 1984.
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Percent of Coronary Artery Segments With Disease
At Autopsy Examination
Arnett EN, Isner JM, Redwood DR et al Ann Int
Med 91350, 1979.
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Impact of the Length of a Stenosis on Flow
Freisinger GC, Hillis WS Am Heart J 92737,
1976. As adapted by Marcus ML The Coronary
Circulation in Health and Disease, Mcgraw Hill
Book Co, 1983.
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Does Visual Interpretation of Coronary Angiogram
Predict Flow?
Peak coronary blood flow as measured directly in
OR at time of bypass surgery, vs stenosis as
assessed at coronary angiography
White C et al NEJM 310819, 1984
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Percent Stenosis Poor Predictor of Flow
23 Patients with Proximal LAD Stenosis
Harrison DG, White CW, Hiratzka LF et al
Circulation 691111, 1984
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Minimal Luminal Cross Sectional Area Predicts
Peak Flow
23 Patients with Proximal LAD Stenosis
Harrison DG, White CW, Hiratzka LF et al
Circulation 691111, 1984
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Percent Stenosis
Although percent diameter stenosis is very
helpful in predicting the physiologic effects of
an experimentally produced obstruction in an
otherwise normal coronary vessel, the
applicability of this index to clinical coronary
disease, which usually is diffuse, has been
seriously challenged particularly in lesions of
intermediate severity. Unfortunately, most
coronary angiographers and clinicians have
continued to use visual estimates of percent
diameter stenosis to separate physiologically
significant from functionally unimportant
obstructions.
Markus ML, Skorton DJ, Johnson MR, et al JACC
11882, 1988.
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The Endocardium
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Myocardial Oxygen SupplyPerfusion Pressure and
Resistance
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The Endocardium
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Coronary blood flow at rest is greater in the
endocardial layer than the epicardium, reflecting
the increased R3 component of resistance in the
endocardium.
Mueller TM, Marcus ML Kerber RE et al Circ Res
42 543, 1978. As adapted by Marcus ML The
Coronary Circulation in Health and Disease
McGraw Hill Book Company, 1983.
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The Endocardium
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Systolic Coronary Blood Flow
Left Ventricle
Right Ventricle
Hess DS and Bache RJ, Circ Research 4588, 1979
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The Endocardium
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Volume of Arterial Vessels Is Greatest In The
Endocardial Layer
Wusten B, Buss DD, Deist H, et al Vasc Res
Cardiol 72636, 1977 Adapted by Marcus ML The
Coronary Circulation in Health and Disease
McGraw Hill Book Company, 1983
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The Endocardium
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Myocardial Oxygen SupplyExercise