What is the pathophysiology of coronary microvascular dysfunction (CMVD)?

From the Guidelines

Coronary microvascular dysfunction (CMD) is characterized by structural and functional abnormalities in the small coronary blood vessels, leading to impaired blood flow regulation and myocardial ischemia despite patent epicardial coronary arteries. The pathophysiology of CMD centers on endothelial dysfunction, where damaged endothelial cells fail to produce adequate nitric oxide, leading to impaired vasodilation 1. Vascular smooth muscle dysfunction also occurs, causing abnormal vasoconstriction and reduced coronary flow reserve. Structural changes like microvascular remodeling, rarefaction (reduction in capillary density), and perivascular fibrosis further compromise blood flow. Inflammation plays a key role through increased oxidative stress and pro-inflammatory cytokines that damage the microvascular endothelium 1. Autonomic nervous system imbalance contributes through excessive sympathetic activation.

Key mechanisms of CMD include:

• Endothelial dysfunction, leading to impaired vasodilation
• Vascular smooth muscle dysfunction, causing abnormal vasoconstriction
• Structural changes, such as microvascular remodeling and rarefaction
• Inflammation, through increased oxidative stress and pro-inflammatory cytokines
• Autonomic nervous system imbalance, through excessive sympathetic activation

Risk factors for CMD include traditional cardiovascular risk factors (hypertension, diabetes, dyslipidemia), female sex (particularly post-menopausal), and systemic inflammatory conditions 1. The diagnosis of CMD can be made using intracoronary pressure and flow measurements, including coronary flow reserve (CFR) and index of microvascular resistance (IMR) 1. A decreased CFR (<2.5) and increased IMR (≥25) indicate microvascular dysfunction.

The clinical presentation of CMD includes chest pain and other cardiac symptoms, despite patent epicardial coronary arteries. The management of CMD should focus on addressing the underlying pathophysiological mechanisms, including endothelial dysfunction, vascular smooth muscle dysfunction, and inflammation, as well as managing traditional cardiovascular risk factors.

From the Research

Pathophysiology of Coronary Microvascular Dysfunction

The pathophysiology of coronary microvascular dysfunction is complex and involves multiple mechanisms, including:

• Impaired flow augmentation in response to pharmacological vasodilators 2
• Abnormal coronary perfusion during exercise 2
• Endothelial injury and dysfunction, leading to arteriolar vasomotor dysfunction 3
• Inflammation, oxidative stress, insulin resistance, hyperlipidemia, hypertension, and shear stress, which can dysregulate coronary endothelial homeostasis and arteriolar vasomotor function 3
• Structural and functional changes in the coronary microvasculature, including diminished coronary flow reserve and increased microvascular resistance 2, 4

Clinical Implications

Coronary microvascular dysfunction is associated with adverse outcomes, including:

• Heart failure with preserved ejection fraction 4
• Hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes 4
• Ischemia and no obstructive coronary artery disease (INOCA), particularly in women 4, 5
• Diminished quality of life and increased symptoms, such as angina 5

Diagnostic and Therapeutic Considerations

Diagnostic modalities for coronary microvascular dysfunction include:

• Invasive coronary function testing 4, 5
• Non-invasive diagnostic modalities, such as cardiac magnetic resonance imaging 2 Therapeutic options for coronary microvascular dysfunction aim to improve symptoms and myocardial blood flow, and include:
• Stratified medical therapy guided by invasive coronary function testing 4
• Ongoing investigations to develop therapy to improve adverse outcomes related to coronary microvascular dysfunction 4