Coronary Microvascular Dysfunction - Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy

Abstract

Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.

Figure 1.

Comparison of cardiovascular event rates and deaths between WISE and WTH patients. CV, cardiovascular; HF, heart failure; MI, myocardial infarction; WISE, Women’s Ischemia Syndrome Evaluation study; WTH, Women Take Heart study. Modified with permission from Gulati M, et al.

Figure 2.

Anatomy of coronary macrovascular and microvascular circulation: epicardial coronary artery (solid arrow) dilates in response to nitroglycerin, acetylcholine, shear stress; intramyocardial arterioles (striped arrow) are responsive to local metabolites and responsible for metabolic regulation of coronary blood flow.

Figure 3.

Cardiac magnetic resonance perfusion images demonstrating dark-rim artifact (red arrows) eliminated by high radial acquisition in a normal control subject, and improved subendocardial border delineation (green arrows) in a WISE subject. WISE, Women’s Ischemia Syndrome Evaluation study.

Figure 4.

Proposed diagnostic criteria of coronary dysfunction using reactivity testing. CBF, coronary blood flow; CFR, coronary flow reserve; EKG, electrocardiography.

Figure 5.

Coronary angiograms and coronary reactivity testing: baseline (A); severe abnormal vasoconstriction (arrow) in response to acetylcholine (B); resolution of vasoconstriction with intracoronary nitroglycerin (C).