Myocardial Ischemia: View from the Vessel Wall

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Myocardial IschemiaView from the Vessel Wall
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Causes of inadequate myocardial O2 supply

• Limited flow in epicardial coronary arteries
• Flow-limiting lesion(s) in conduit vessels
• Exacerbated by impaired endothelium-dependent
  response to stress
• Reduced dilation
• Constriction
• Impaired microvascular coronary flow reserve
• Resistance vessel (lt200 µm diameter) dysfunction
• Disordered VSMC activation/contraction
• Abnormal motility
• Abnormal growth
• Inflammation
• Extravascular compression

Pepine CJ et al. J Am Coll Cardiol.
20064730S-5. Reis SE et al. J Am Coll Cardiol.
1999331469-75. Kerins DM et al. In Goodman and
Gilmans The Pharmacological Basis of
Therapeutics. 10th ed.
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Ischemia is related to myocardial O2 supply and
demand
Heart rate
Diastolic time
Spasm/ autoreg.
Oxygen demand
Oxygen supply
Contractility
Coronary blood flow
Collaterals
Wall tension
AoP LVED gradient
Systolicpressure
Volume
LVEDP
Ao dias. pressure
Ischemia
Adapted from Morrow DA et al. In Braunwalds
Heart Disease. 7th ed.
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Symptoms occur at end of ischemic cascade
Abnormalities evolving during ischemia

• Approximately ½ of patients with angina also
  experience episodes of asymptomatic (silent)
  ischemia
• Many episodes of ischemia never become painful

Angina
? ST
? Filling
Magnitude of ischemia
Systolic dysfunction
? Relaxation (diastolic dysfunction)
0
30
Duration of ischemia (sec)
Cohn PF et al. Circulation. 20031081263-77.Adap
ted from Kern MJ. In Braunwalds Heart Disease.
7th ed.
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Obstructive plaque and ischemia
Obstructiveatheroscleroticplaque
Fattystreak
Increasedplaque
Normal
Plaque
Exertionalangina
Noninvasive tests normal
Noninvasive tests abnormal
? Vasodilator response to stress
Adapted from Abrams J. N Engl J Med.
20053522524-33.
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Impaired microvascular perfusion in the anginal
syndrome

Diminished microvascular perfusion ?
P lt 0.001
P 0.002
P 0.02
P NS
Control (n 10)
Chest pain with normal coronary angiogram (n
20)
Panting JR et al. N Engl J Med. 20023461948-53.
Assessed via magnetic resonance imaging
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Subendocardial hypoperfusion Association with
anginal syndrome
MRI of myocardium during first pass of gadolinium

• At rest
• During stress (adenosine infusion)

Healthy control
Patient withchest pain and angiographically
normal coronary arteries
Panting JR et al. N Engl J Med. 20023461948-53.
Magnetic resonance imaging
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Accumulating evidence implicates coronary
microcirculation dysfunction in IHD

• Wide variability in effort tolerance over time
• Large scatter between stenosis severity and flow
  reserve
• Reduced flow responses to stress in regions
  perfused by non-stenotic vessels
• Variability in outcome after successful
  intervention
• 25 of cases with biomarker-positive ACS have no
  flow-limiting stenosis
• Predictive value of ? BNP and ? CRP for adverse
  outcomes in ACS
• Plaque erosion with microvascular embolization

Pepine CJ et al. J Am Coll Cardiol. 20064730S-5.