Coronary Physiology and Microvascular Dysfunction in Ischemia with Non-Obstructive Coronary Arteries: Advances and Challenges

Dear Colleagues,

Our understanding of ischemic heart disease has evolved considerably, revealing that a significant proportion of patients experience angina despite the absence of significant stenosis in the epicardial coronary arteries. This Special Issue, titled “Coronary Physiology and Microvascular Dysfunction in Ischemia with Non-Obstructive Coronary Arteries: Advances and Challenges”, aims to underscore the crucial role of coronary microcirculation and to provide novel insights into coronary physiology that are reshaping cardiovascular diagnostics and management.

Coronary microvascular dysfunction (CMD) is now widely recognized as a major cause of angina and ischemia in patients without obstructive coronary artery disease (ANOCA/INOCA). Its underlying mechanisms are complex and multifactorial, involving both structural remodeling—such as arteriolar stenosis, perivascular fibrosis, and capillary rarefaction—and functional alterations, including endothelial dysfunction, impaired vasodilation, and microvascular spasm. These changes can significantly reduce myocardial perfusion, resulting in ischemic symptoms. Beyond angina, CMD contributes to a broad spectrum of cardiovascular conditions, including heart failure with preserved ejection fraction (HFpEF), myocardial infarction with non-obstructive coronary arteries (MINOCA), Takotsubo syndrome, and hypertrophic cardiomyopathy.

Recent advances in coronary physiology—particularly through invasive methods such as thermodilution-derived coronary flow reserve (CFR) and the index of microvascular resistance (IMR), along with newer indices like the resistive reserve ratio (RRR), angiography-derived IMR (angio-IMR), microvascular resistance reserve (MRR), and quantitative flow ratio (QFR)—have greatly enhanced our ability to identify and characterize CMD. At the same time, non-invasive imaging modalities such as positron emission tomography (PET), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) offer valuable insights into coronary microvascular function and support a more holistic, patient-centered diagnostic approach.

Despite these significant advancements, INOCA remains substantially underdiagnosed and undertreated in clinical practice, highlighting the urgent need for increased awareness and broader implementation of advanced diagnostic tools.

This Special Issue welcomes original research articles, preclinical studies, comprehensive reviews, and clinical investigations, including both systematic and narrative reviews. We particularly encourage submissions focused on novel diagnostic and imaging approaches, the molecular and cellular mechanisms underlying CMD, therapeutic innovations, and the integration of artificial intelligence into cardiovascular medicine. Of special interest is research advancing precision and personalized approaches to the diagnosis, prevention, and treatment of CMD.

By bringing together cutting-edge research and diverse clinical perspectives, this Special Issue seeks to deepen scientific understanding, optimize diagnostic and therapeutic strategies, and improve outcomes for this often-overlooked yet clinically significant patient population.

Dr. Kyriakos Dimitriadis
Guest Editor

Dr. Athanasios Sakalidis
Guest Editor Assistant

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• coronary physiology
• coronary microvascular dysfunction
• coronary flow reserve
• ischemia with no obstructive arteries
• coronary microcirculation
• myocardial infarction with non-obstructive coronary arteries
• microvascular angina
• thermodilution
• stable angina