Abstract

Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. Impairment of this mechanism, defined as coronary microvascular dysfunction (CMD), carries an increased risk of adverse cardiovascular clinical outcomes. Coronary endothelial dysfunction accounts for approximately two-thirds of clinical conditions presenting with symptoms and signs of myocardial ischemia without obstructive coronary disease, termed “ischemia with non-obstructive coronary artery disease” (INOCA) and for a small proportion of “myocardial infarction with non-obstructive coronary artery disease” (MINOCA). More frequently, the clinical presentation of INOCA is microvascular angina due to CMD, while some patients present vasospastic angina due to epicardial spasm, and mixed epicardial and microvascular forms. CMD may be associated with focal and diffuse epicardial coronary atherosclerosis, which may reinforce each other. Both INOCA and MINOCA are more common in females. Clinical classification of CMD includes the association with conditions in which atherosclerosis has limited relevance, with non-obstructive atherosclerosis, and with obstructive atherosclerosis. Several studies already exist which support the evidence that CMD is part of systemic microvascular disease involving multiple organs, such as brain and kidney. Moreover, CMD is strongly associated with the development of heart failure with preserved ejection fraction (HFpEF), diabetes, hypertensive heart disease, and also chronic inflammatory and autoimmune diseases. Since coronary microcirculation is not visible on invasive angiography or computed tomographic coronary angiography (CTCA), the diagnosis of CMD is usually based on functional assessment of microcirculation, which can be performed by both invasive and non-invasive methods, including the assessment of delayed flow of contrast during angiography, measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), evaluation of angina induced by intracoronary acetylcholine infusion, and assessment of myocardial perfusion by positron emission tomography (PET) and magnetic resonance (CMR).

Highlights

  • Typical angina or atypical symptoms such as exertional dyspnea or episodes of chest pain at rest, are often experienced by patients with coronary artery diseases (CAD) [1,2,3]

  • Since coronary microcirculation is beyond the resolution of invasive and non-invasive coronary angiography, the diagnosis of coronary microvascular dysfunction (CMD) is based on functional assessment of the coronary arteries, which can be performed using both invasive and non-invasive methods

  • A substantial proportion of patients with chest pain undergoing diagnostic coronary angiography do not show significant obstructive coronary lesions. Most of these patients have a combination of functional and structural abnormalities of coronary microcirculation strongly associated with endothelial dysfunction

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Summary

Introduction

Typical angina or atypical symptoms such as exertional dyspnea or episodes of chest pain at rest, are often experienced by patients with coronary artery diseases (CAD) [1,2,3]. A substantial proportion (over 50%) of symptomatic patients without flow-limiting coronary lesions have structural or functional abnormalities of the coronary microcirculation leading to impaired vasodilatation, which contributes to myocardial ischemia [17]. The prognosis of non-obstructive CAD was thought to be benign, and patients were often inappropriately reassured, without further investigation, despite clinical features requiring coronary angiography. Instead, this condition represents a major cause for myocardial ischemia and is associated with a high risk of major adverse cardiovascular events, including MI, progressive heart failure, stroke, and even sudden death [10,14,24,25,26,27,28]. CMD is a strong determinant of prognosis even in patients with coronary stenosis of intermediate severity [31]

Distribution of Blood Flow
Heterogeneity of Coronary Microcirculation
Collaterals
Pathophysiology of CMD
Endothelial Dysfunction
Autonomic Nervous System
Clinical Presentation
Gender Differences in CMD
Clinical Classification
CMD without Atherosclerosis
CMD with Non-Obstructive Atherosclerosis
CMD in the Development of HFpEF
Microvascular Disease of the Brain
CMD in Diabetes
CMD in Hypertensive Heart Disease
CMD in Aortic Valve Stenosis
CMD in Chronic Inflammatory and Autoimmune Diseases
CMD with Obstructive Atherosclerosis
Epicardial Effects on Microcirculation
Coronary No-Reflow
Microvascular Effects on Epicardial Coronary Arteries
Diagnosis of CMD
Invasive Diagnosis
Non-Invasive Diagnosis
Treatment of CMD
Findings
10. Conclusions
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