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Myocardial Ischemia: View from the Vessel Wall

Myocardial Ischemia: View from the Vessel Wall. Causes of inadequate myocardial O 2 supply. Limited flow in epicardial coronary arteries Flow-limiting lesion(s) in conduit vessels Exacerbated by impaired endothelium-dependent response to stress Reduced dilation C onstriction

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Myocardial Ischemia: View from the Vessel Wall

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  1. Myocardial Ischemia:View from the Vessel Wall

  2. 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 (<200 µm diameter) dysfunction • Disordered VSMC activation/contraction • Abnormal motility • Abnormal growth • Inflammation Extravascular compression Pepine CJ et al. J Am Coll Cardiol. 2006;47:30S-5. Reis SE et al. J Am Coll Cardiol. 1999;33:1469-75. Kerins DM et al. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed.

  3. Ischemia is related to myocardial O2 supply and demand Heart rate Diastolic time Spasm/ autoreg. Contractility Coronary blood flow Oxygen demand Oxygen supply Collaterals Wall tension AoP – LVED gradient Systolicpressure Volume Ischemia LVEDP Ao dias. pressure Adapted from Morrow DA et al. In: Braunwald’s Heart Disease. 7th ed.

  4. 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. 2003;108:1263-77.Adapted from Kern MJ. In: Braunwald’s Heart Disease. 7th ed.

  5. 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. 2005;352:2524-33.

  6. Impaired microvascular perfusion in the anginal syndrome Diminished microvascular perfusion  P < 0.001 P = 0.002 P = 0.02 P = NS Control (n = 10) Chest pain with normal coronary angiogram (n = 20) *Assessed via magnetic resonance imaging Panting JR et al. N Engl J Med. 2002;346:1948-53.

  7. 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 Magnetic resonance imaging Panting JR et al. N Engl J Med. 2002;346:1948-53.

  8. 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. 2006;47:30S-5.

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