Ischemia with nonobstructive coronary arteries: Insights into diagnostic approaches

Ischemia with nonobstructive coronary arteries (INOCA) is a clinically significant yet underrecognized condition characterized by anginal symptoms and evidence of myocardial ischemia in the absence of obstructive coronary artery disease. Once considered benign, INOCA is now associated with adverse outcomes such as myocardial infarction and heart failure. 1 This narrative review synthesizes current understanding of the multifactorial pathophysiology underlying INOCA, including coronary microvascular dysfunction (CMD), epicardial coronary vasospasm, endothelial dysfunction, hormonal influences, and autonomic nervous system imbalance. Diagnostic challenges are explored, highlighting the utility of both invasive and noninvasive modalities (e.g. coronary flow reserve, index of microcirculatory resistance, acetylcholine provocation testing, cardiac PET, MRI, and single-photon emission computed tomography). Evidence-based management strategies are discussed with emphasis on mechanism-targeted pharmacologic therapy, alignment of treatments with specific pathophysiological processes, emerging interventions (such as Rho-kinase inhibitors), and lifestyle modifications. By identifying knowledge gaps, this review provides a narrative overview of current diagnostic approaches and management options for INOCA, while underscoring areas of ongoing research and clinical uncertainty.