Coronary Microvascular Dysfunction in ANOCA and INOCA: From Pathophysiological Endotypes to Precision Diagnosis and Treatment.

Abstract

Coronary microvascular dysfunction (CMD) is an important cause of angina and myocardial ischemia in patients without obstructive coronary artery disease and contributes substantially to the clinical spectrum of angina with non-obstructive coronary arteries (ANOCA) and ischemia with non-obstructive coronary arteries (INOCA). These conditions represent a heterogeneous group of coronary vasomotor disorders in which structural and functional abnormalities of the coronary microcirculation, endothelial dysfunction, coronary vasospasm, and diffuse non-obstructive atherosclerosis may occur alone or in combination. This review summarizes current knowledge on the pathophysiology, diagnosis, and management of CMD in patients with ANOCA and INOCA. We discuss the distinction between ANOCA and INOCA, the principal coronary functional endotypes, and the mechanisms responsible for impaired coronary microvascular function. We also review contemporary diagnostic approaches, including non-invasive imaging and invasive coronary function testing, with emphasis on their complementary roles in identifying the underlying mechanism of ischemia. Current management strategies are presented from a mechanism-based perspective, including lifestyle modification, pharmacological therapy, endotype-guided treatment, and emerging therapeutic approaches. Improved understanding of coronary functional abnormalities has shifted clinical evaluation beyond the exclusion of obstructive coronary artery disease toward identification of the mechanism responsible for persistent symptoms and ischemia. Continued advances in disease phenotyping, coronary function testing, and targeted therapies are expected to support more individualized management and improve outcomes in this diverse patient population.