Vasospastic and Microvascular Coronary Artery Disease
Attilio Maseri, MD
University Vita-Salute San Raffaele – Milan, Italy
15th GWICC Beijing, October 2004
Coronary Vasoconstriction
Coronary perfusion can be transiently or persistently impaired by coronary vasoconstriction resulting in myocardial ischemia.
Vasoconstriction may occur in large coronary arteries and in the microcirculation.
Vasoconstriction of Epicardial Coronary Arteries
Coronary vasomotion modulates residual coronary flow reserve, resulting in a variable effort tolerance when stenosing plaques have a preserved muscular media which can vary the residual lumen
Coronary Artery Spasm
Coronary spasm can cause persistent coronary occlusion when associated with local thrombosis, resulting in acute infarction
Soon after acute MI, intracoronary acetilcoline cause coronary spasm in about 60% of Japanese patients, but only in 20% of Italians
Pristipino et al, Circulation 2000; 101:1102-1108
Vasoconstriction of Epicardial Coronary Arteries
Variant angina is typically characterized by angina at rest, particularly at night or in the morning, in the presence of a normal effect tolerance, but often causes infarction and fatal arrhythmias
Suspicion of Variant Angina
Predominantly spontaneous attacks with preserved effort tolerance, often in clusters of 2-3
Predominantly spontaneous attacks with preserved effort tolerance, often in clusters of 2-3
Lasting 1-10 mins, relieved by GTN
Predominantly spontaneous attacks with preserved effort tolerance, often in clusters of 2-3
Lasting 1-10 mins, relieved by GTN
Often at night or early morning with waxing and waning over periods of weeks and months
Predominantly spontaneous attacks with preserved effort tolerance, often in clusters of 2-3
Lasting 1-10 mins, relieved by GTN
Often at night or early morning with waxing and waning over periods of weeks and months
Sometimes associated with syncope
Negative exercise test after GTN
Prevalence of Variant Angina
Pisa, London, Rome = 1.0% of admissions
Diagnosed only after weeks, months or years
Rome (1991-96): 64 cases aged 19-75 years
60% had normal angiograms ? 40% major events
40% had stenosis ? 6% major events
Pathogenetics Mechanisms of Spasm
A local coronary hyper-response Hackett 1986
Hence: a smooth muscle post-receptorial alteration Maseri 1990
Provocation by stimuli acting on different receptors:
Ergonovine Higgins 1976
Metacholine Endo 1976
Dopamine Crea 1986
Hystamine Ginsburg 1981- Kaski 1986
Acetylcholine Yasue 1986
Serotonin Mc Fadden 1991
Treatment of Variant Angina
Reduce aspecifically smooth muscle constrictor response by nitrates and calcium-antagonists
Sometimes very high doses required
Frenneaux et al. Am J Cardiol 1988;62:832
Lefroy et al. Coronary artery disease 1992;3:745
Pace-maker, implantable defibrillator
Microvascular Constriction
This syndrome includes 60-70% of women (about 60% post-menopausal and 40% pre-menopausal) but also 30-40% of men.
It is characterized by angina pectoris and ‘normal’ coronary angiography.
Its incidence may vary from 10% to 50% of patients submitted to coronary arteriography.
The diagnosis of myocardial ischemia is difficult for a number of reasons.
In spite of the absence of increased risk of infarction and cardiac death, these patients may be crippled by pain.
Syndrome X: PROBLEM
The inconsistent response to nitrates and anti-anginal drugs and to non conventional anti-ischemic therapy, indicates the need for research on multiple, potential causes of coronary vascular dysfunction, in order to develop rational forms of therapy.
Suspicion of Microvascular Angina
Long-lasting (>10-30’), poorly responsive to GTN
Transient ECG changes or positive myocardial scintigraphy ? Cardiac origin of pain
No evidence of left ventricular dysfunction
Worsening of exercise test following GTN
Lanza et al, Circulation 1994
Mechanisms of Microvascular Angina
No flow limiting stenosis
Prearterioles 0.1 mm
Conduit
Distribution
Epicardial 0.5 mm
Endo
Epi
Arterioles < 0.1 mm
Metabolic flow control
Maseri A et al, JACC 1991; 17: 499-506
Maseri A et al, AJC 1992; 70: 1602-1605
Myocardial Phosphorus-31 NMR Spectroscopy
in women with angina and normal coronary arteries
Buchthal SD et al, NEJM 2000; 342
Ischemia-reperfusion damage after pacing
in patients with cardiac syndrome X
Buffon A et al, Am J Physiol Heart Circ Physiol 2000; 279
Subendocardial perfusion reserve index in patients with syndrome X is reduced
Panting JR et al, NEJM 2002
Evidence of Myocardial Ischemia
NPY ? Clarke et al, Lancet 1977
Endothelin ? Larkin et al, Am J Cardiol 1989
Altered adrenergic function ? Lanza et al, Circulation 1997
Serotonin ? Mc Fadden et al, NEJM 1991
Acetylcholine ? Neumann et al, Am J Cardiol 1990
Na+/H+ exchanger upregulation ? Karen et al, Eur Heart J 1997
Potential Causes &n