Transcript Contemporary Management of Myocardial Ischemia

Myocardial Ischemia:
View from the Vessel Wall
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.
Ischemia is related to myocardial O2 supply
and demand
Diastolic
time
Heart rate
Contractility
Oxygen
demand
Oxygen
supply
Coronary
blood flow
Collaterals
Wall tension
Systolic
pressure
Spasm/
autoreg.
AoP – LVED
gradient
Volume
Ischemia
LVEDP
Ao dias.
pressure
Adapted from Morrow DA et al. In: Braunwald’s Heart Disease. 7th ed.
Symptoms occur at end of ischemic cascade
Abnormalities
evolving during
ischemia
• Approximately
½ of patients with
angina also
experience
episodes of
asymptomatic
(silent) ischemia
Angina
 ST
 Filling
Magnitude
of ischemia
Systolic
dysfunction
• Many episodes
of ischemia never
become painful
 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.
Obstructive plaque and ischemia
Normal
Fatty
streak
Plaque
Increased
plaque
Obstructive
atherosclerotic
plaque
Exertional
angina
Noninvasive tests:
normal
Noninvasive tests:
abnormal
 Vasodilator response to stress
Adapted from Abrams J. N Engl J Med. 2005;352:2524-33.
Impaired microvascular perfusion in the anginal
syndrome
Diminished microvascular perfusion
0.2
Myocardial
perfusion
index*
P = 0.02
P = 0.002
Endocardium
Epicardium

P < 0.001
P = NS
0.1
0
Control (n = 10)
Rest
Endocardium
Epicardium
Chest pain with
normal coronary angiogram (n = 20)
Adenosine infusion
*Assessed via magnetic resonance imaging
Panting JR et al. N Engl J Med. 2002;346:1948-53.
Subendocardial hypoperfusion: Association
with anginal syndrome
MRI of myocardium during first pass of gadolinium
A. At rest
Healthy control
B. During stress
(adenosine infusion)
Patient with
chest pain and
angiographically
normal coronary
arteries
Magnetic resonance imaging
Panting JR et al. N Engl J Med. 2002;346:1948-53.
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.