Invasive Evaluation and Phenotype-Guided Treatment of ANOCA in Women

Overview

This prospective single-center interventional study will include women with angina and non-obstructive coronary arteries. Participants will undergo a standardized invasive coronary assessment combining coronary physiology, acetylcholine provocation testing, and optical coherence tomography. The diagnostic protocol will identify functional and morphological mechanisms of angina, including microvascular dysfunction, epicardial vasospasm, microvascular spasm, endothelial dysfunction, functional epicardial disease, combined mechanisms, or normal coronary physiology. Based on the identified phenotype, participants will receive individualized multidisciplinary treatment, including targeted pharmacological therapy, adapted cardiovascular rehabilitation, and psycho-emotional support when indicated. Clinical follow-up will be performed at 1, 6, and 12 months to assess angina symptoms, quality of life, functional capacity, adherence to treatment, and cardiovascular events.

Angina with non-obstructive coronary arteries (ANOCA) is a prevalent and frequently underdiagnosed clinical condition, particularly in women. Although obstructive epicardial coronary artery disease is absent, symptoms may be related to coronary microvascular dysfunction, epicardial or microvascular vasospasm, endothelial dysfunction, non-obstructive atherosclerotic plaque, myocardial bridging, or combined mechanisms. In routine clinical practice, many patients remain without a precise pathophysiological diagnosis after conventional angiography. This study will evaluate a structured diagnostic and therapeutic pathway for women with ANOCA at a single academic cardiovascular center in Uruguay. Eligible participants will undergo an invasive coronary assessment performed during cardiac catheterization. The protocol will include angiographic confirmation of non-obstructive coronary arteries, invasive coronary physiology assessment, acetylcholine provocation testing for coronary vasomotor disorders, and optical coherence tomography for intracoronary morphological assessment. The invasive findings will be integrated to classify participants according to their predominant functional and/or morphological phenotype. Potential phenotypes include coronary microvascular dysfunction, epicardial vasospasm, microvascular spasm, endothelial dysfunction, functional epicardial disease, non-obstructive plaque-related abnormalities, combined mechanisms, or normal invasive coronary physiology. After phenotyping, participants will receive an individualized treatment plan according to the identified mechanism. This may include targeted pharmacological therapy, cardiovascular risk factor optimization, adapted cardiovascular rehabilitation, and structured psycho-emotional support when clinically indicated. The therapeutic strategy will be determined by the treating clinical team according to the study protocol and current evidence-based recommendations. Participants will be followed for 12 months after the invasive assessment. Follow-up visits will assess angina symptoms, health-related quality of life, functional capacity, treatment adherence, adverse events, and cardiovascular outcomes. The study aims to generate local evidence on the feasibility and clinical utility of a phenotype-guided approach for women with ANOCA and to support the development of a multidisciplinary reference pathway for this condition in Uruguay.