The Coronary Circulation in Hypertrophy and in Syndrome X

Summary

Although the contribution of epicardial coronary artery disease in ischemic syndromes is incontrovertible, in recent years much interest has shifted to the pathophysiologic relevance of disease or dysfunction of the coronary microcirculation (defined as intramyocardial arteries and arterioles too small to be visualized angiographically). Animal studies have shown the major contribution of intramyocardial arteries, proximal to the arteriolar bed, to coronary resistance, limitations in coronary flow reserve, and impaired coronary autoregulation in experimental left ventricular hypertrophy, and have shown evidence for microvascular endothelial dysfunction in early atherosclerosis. Despite imperfect techniques for measurement of coronary blood flow in humans, several studies have shown limitations in coronary flow reserve in familial hypertrophic cardiomyopathy and pressure-induced left ventricular hypertrophy that may be causally related to inducible myocardial ischemia in these patients. Mechanisms for impaired coronary flow reserve in hypertrophy are likely multifactorial and may include increased resting and stress-induced coronary flow requirements without neovascularization, detrimental effects of abnormal diastolic relaxation on intramyocardial coronary flow, and medial and intimal thickening of intramyocardial coronary arteries. More controversial is the presence and significance of coronary microvascular dysfunction in patients with chest pain syndromes in the absence of left ventricular hypertrophy, often with abnormal noninvasive testing, and designated as Syndrome X or microvascular angina. Although several studies have shown limited coronary flow responses to pacing or pharmacologic vasodilators, and heightened sensitivity of the coronary microcirculation to ergonovine in this patient population, proof that these altered coronary flow dynamics truly cause myocardial ischemia during stress has been elusive. Selection of patients on the basis of abnormal radionuclide studies may be more fruitful in making the connection between abnormal coronary flow dynamics and inducible myocardial ischemia than selection of patients on the basis of their exercise EKG. Coronary artery disease may also be associated with coronary microvascular dysfunction, and hypercholesterolemia and hypertension, which are commonly associated with obstructive coronary artery disease, also adversely affect the coronary microcirculation. Such involvement may explain why a subset of patients continue to have symptoms and evidence of inducible ischemia despite adequate revascularization by percutaneous transluminal coronary angioplasty or coronary bypass grafting. Further studies will undoubtedly clarify the mechanisms and the extent of coronary microvascular dysfunction in ischemic syndromes, in addition to clarifying suitable therapeutic interventions.