Invasive Evaluation and Phenotype-Guided Treatment of ANOCA in Women

Official title

Invasive Functional and Morphological Coronary Assessment Followed by Phenotype-Guided Multidisciplinary Treatment in Women With Angina and Non-Obstructive Coronary Arteries: A Prospective Single-Center Interventional Study

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.

Detailed description

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.

Interventions

• Procedure Invasive Coronary Functional and Morphological Assessment
  Participants will undergo invasive coronary assessment including coronary physiology measurements, acetylcholine provocation testing, and optical coherence tomography to identify functional and morphological mechanisms of angina with non-obstructive coronary arteries.
• Drug Pharmacological treatment will be individualized according to the invasive coronary phenotype identified. Treatment may include antianginal therapy, vasodilator therapy, endothelial function-targeted
  Pharmacological treatment will be individualized according to the invasive coronary phenotype identified. Treatment may include antianginal therapy, vasodilator therapy, endothelial function-targeted therapy, cardiovascular risk factor optimization, or revascularization evaluation when clinically indicated.

Primary outcome measures

• Change in Angina-Related Health Status Assessed by the Seattle Angina Questionnaire-7 [Time frame: Baseline to 12 months]

Secondary outcome measures (9)

• Change in Health-Related Quality of Life Assessed by the EuroQol 5-Dimension 5-Level Visual Analog Scale [Time frame: Baseline to 12 months]
• Change in Functional Capacity [Time frame: Baseline to 12 months]
• Prevalence of Invasive Coronary Functional Phenotypes [Time frame: At index invasive coronary procedure]
• Prevalence of Coronary Morphological Abnormalities Assessed by Optical Coherence Tomography [Time frame: At index invasive coronary procedure]
• Change in Perceived Stress Assessed by the Perceived Stress Scale-4 [Time frame: Baseline to 6 and 12 months]
• Medication Adherence Assessed by the Modified Morisky-Green-Levine Questionnaire [Time frame: 1, 6, and 12 months]
• Major Adverse Cardiovascular Events [Time frame: Baseline to 12 months]
• Adherence to Cardiovascular Rehabilitation Assessed by Session Completion Rate [Time frame: During the 12-week cardiovascular rehabilitation program.]
• Adherence to Psycho-Emotional Support Assessed by Session Completion Rate [Time frame: 1, 6, and 12 months]

Eligibility criteria

Inclusion criteria

• Female participants aged 35 to 75 years.
• Symptoms compatible with stable angina or suspected myocardial ischemia.
• Non-obstructive coronary arteries, defined as absence of angiographic stenosis greater than or equal to 50%.
• Ability to undergo invasive coronary assessment and clinical follow-up.
• Written informed consent.

Exclusion criteria

• Significant structural heart disease.
• Severe left ventricular systolic dysfunction, defined as left ventricular ejection fraction <40%.
• Clinically relevant contraindication to adenosine or acetylcholine, including severe asthma, untreated high-grade atrioventricular block, or known hypersensitivity.
• Active oncological disease or life expectancy less than 12 months.
• Inability to complete the diagnostic or therapeutic study protocol.
• Participation in another clinical study that could interfere with the present protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Uruguay · 1 center

• Hospital de Clínicas Dr. Manuel Quintela — Montevideo

Publications

• Mila R, Albistur J, Valdez M, Loza G, Torrado J, Bachini J, Murguia S, Acquistapace F, Nobile N, Briano V, Niggemeyer A, Trujillo P, Niell N, Duran A, Alfonso F, Dayan V. "A stratified pathway to stent-free reperfusion: Selecting suitable patients in ST-elevation myocardial infarction". Cardiovasc Revasc Med. 2025 Jun;75:90-97. doi: 10.1016/j.carrev.2024.09.001. Epub 2024 Sep 14. PMID 39306485
• Albistur S, Torrado J, Niell N, Mila R. Microvascular dysfunction following deferred stenting strategy in ST-segment elevation myocardial infarction: a case report. Eur Heart J Case Rep. 2023 Nov 14;7(11):ytad564. doi: 10.1093/ehjcr/ytad564. eCollection 2023 Nov. PMID 38034941
• Larsen AI, Saeland C, Vegsundvag J, Skadberg MS, Nilsen J, Butt N, Ushakova A, Valborgland T, Munk PS, Isaksen K. Aerobic high-intensity interval exercise training in patients with angina and no obstructive coronary artery disease: feasibility and physiological effects. Eur Heart J Open. 2023 Mar 22;3(2):oead030. doi: 10.1093/ehjopen/oead030. eCollection 2023 Mar. PMID 37113515
• Hokimoto S, Kaikita K, Yasuda S, Tsujita K, Ishihara M, Matoba T, Matsuzawa Y, Mitsutake Y, Mitani Y, Murohara T, Noda T, Node K, Noguchi T, Suzuki H, Takahashi J, Tanabe Y, Tanaka A, Tanaka N, Teragawa H, Yasu T, Yoshimura M, Asaumi Y, Godo S, Ikenaga H, Imanaka T, Ishibashi K, Ishii M, Ishihara T, Matsuura Y, Miura H, Nakano Y, Ogawa T, Shiroto T, Soejima H, Takagi R, Tanaka A, Tanaka A, Taruya PMID 36908169
• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the mana PMID 39210710
• Smilowitz NR, Prasad M, Widmer RJ, Toleva O, Quesada O, Sutton NR, Lerman A, Reynolds HR, Kesarwani M, Savage MP, Sweeny JM, Janaszek KB, Barseghian El-Farra A, Holoshitz N, Park K, Albadri A, Blair JA, Jeremias A, Kearney KE, Kobayashi Y, Miner SES, Samuels BA, Shah SM, Taqueti VR, Wei J, Fearon WF, Moses JW, Henry TD, Tremmel JA; Microvascular Network (MVN). Comprehensive Management of ANOCA, Pa PMID 37704316
• Samuels BA, Shah SM, Widmer RJ, Kobayashi Y, Miner SES, Taqueti VR, Jeremias A, Albadri A, Blair JA, Kearney KE, Wei J, Park K, Barseghian El-Farra A, Holoshitz N, Janaszek KB, Kesarwani M, Lerman A, Prasad M, Quesada O, Reynolds HR, Savage MP, Smilowitz NR, Sutton NR, Sweeny JM, Toleva O, Henry TD, Moses JW, Fearon WF, Tremmel JA; Microvascular Network (MVN). Comprehensive Management of ANOCA, Pa PMID 37704315
• Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855 PMID 30266608

Identifiers

NCT: NCT07593157 · FMV_1_2025_1_186667 · FMV_1_2025_1_186667

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗