Ischemia with No Obstructive Coronary Arteries (INOCA): Diagnostic Approaches and Contemporary Treatment Strategies

Ischemia with No Obstructive Coronary Arteries (INOCA) is increasingly recognized as a distinct clinical syndrome characterized by objective evidence of myocardial ischemia in the absence of flow-limiting epicardial coronary artery disease. Once considered a benign finding, INOCA is now known to be associated with persistent symptoms, impaired quality of life, recurrent hospitalizations, and adverse cardiovascular outcomes. The condition is highly prevalent among patients undergoing coronary angiography for angina, with a pronounced predominance in women, underscoring important sex specific pathophysiological mechanisms. INOCA encompasses heterogeneous underlying mechanisms, most notably coronary microvascular dysfunction and epicardial coronary vasospasm, which may occur in isolation or coexist. These abnormalities result in dynamic and context dependent ischemia that is frequently missed by conventional diagnostic pathways focused on obstructive coronary disease. As a result, INOCA remains underdiagnosed and undertreated in routine clinical practice. This review provides a comprehensive and contemporary overview of INOCA, integrating current knowledge on its pathophysiology, clinical presentation, diagnostic strategies, and management approaches. We highlight the limitations of traditional anatomy based evaluation and emphasize the importance of functional and mechanism-oriented diagnostic frameworks, including advanced non-invasive imaging and invasive coronary function testing. Particular attention is given to phenotype-guided therapeutic strategies, encompassing targeted anti-ischemic therapy, endothelial and disease modifying treatments, and lifestyle and non-pharmacological interventions. By synthesizing emerging evidence and clinical insights, this review advocates for a multidisciplinary, personalized approach to INOCA. Adoption of mechanism based diagnostic and therapeutic strategies has the potential to improve symptom control, optimize long-term outcomes, and align INOCA management with the principles of modern, patient centered cardiovascular care.