Invasive Evaluation and Phenotype-Guided Treatment of ANOCA in Women

NCT07593157 | Not Yet Recruiting

• 1 other identifier: FMV_1_2025_1_186667
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ANOCA - Angina With Non-obstructive Coronary Arteries; Vasospastic Angina; Coronary Microvascular Dysfunction (CMD)

Keywords

Angina with non-obstructive coronary arteries; ANOCA; INOCA; Vasospastic angina; Coronary Microvascular Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change in Angina-Related Health Status Assessed by the Seattle Angina Questionnaire-7

  Change in Seattle Angina Questionnaire-7 score from baseline to 12-month follow-up after invasive coronary phenotyping and phenotype-guided multidisciplinary treatment. The Seattle Angina Questionnaire-7 is a 7-item patient-reported outcome measure assessing angina-related health status. Scores range from 0 to 100, with higher scores indicating better angina-related health status and fewer symptoms.

  Baseline to 12 months

Secondary Outcomes (9)

• Change in Health-Related Quality of Life Assessed by the EuroQol 5-Dimension 5-Level Visual Analog Scale

  Baseline to 12 months

• Change in Functional Capacity

  Baseline to 12 months

• Prevalence of Invasive Coronary Functional Phenotypes

  At index invasive coronary procedure

• Prevalence of Coronary Morphological Abnormalities Assessed by Optical Coherence Tomography

  At index invasive coronary procedure

• Change in Perceived Stress Assessed by the Perceived Stress Scale-4

  Baseline to 6 and 12 months

Study Arms (1)

Phenotype-Guided Diagnostic and Therapeutic Strategy

EXPERIMENTAL

Participants will undergo a standardized invasive coronary assessment to identify functional and morphological mechanisms of angina with non-obstructive coronary arteries. Based on the identified phenotype, participants will receive individualized treatment including targeted pharmacological therapy, adapted cardiovascular rehabilitation, and psycho-emotional support when clinically indicated.

Procedure: Invasive Coronary Functional and Morphological Assessment; Drug: Pharmacological treatment will be individualized according to the invasive coronary phenotype identified. Treatment may include antianginal therapy, vasodilator therapy, endothelial function-targeted

Interventions

Invasive Coronary Functional and Morphological Assessment PROCEDURE

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.

Phenotype-Guided Diagnostic and Therapeutic Strategy

Pharmacological treatment will be individualized according to the invasive coronary phenotype identified. Treatment may include antianginal therapy, vasodilator therapy, endothelial function-targeted DRUG

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.

Phenotype-Guided Diagnostic and Therapeutic Strategy

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clínicas Dr. Manuel Quintela: lead

Study Sites (1)

Hospital de Clínicas Dr. Manuel Quintela

Montevideo, Montevideo Department, 11600, Uruguay

Location

Related Publications (8)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 A, Tsuda E, Wakabayashi K, Yokoi K, Minamino T, Nakagawa Y, Sueda S, Shimokawa H, Ogawa H; Japanese Circulation Society and Japanese Association of Cardiovascular Intervention and Therapeutics and Japanese College of Cardiology Joint Working Group. JCS/CVIT/JCC 2023 Guideline Focused Update on Diagnosis and Treatment of Vasospastic Angina (Coronary Spastic Angina) and Coronary Microvascular Dysfunction. Circ J. 2023 May 25;87(6):879-936. doi: 10.1253/circj.CJ-22-0779. Epub 2023 Apr 6. No abstract available.

  PMID: 36908169 BACKGROUND

• 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 management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

  PMID: 39210710 BACKGROUND

• 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, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1264-1279. doi: 10.1016/j.jacc.2023.06.044.

  PMID: 37704316 BACKGROUND

• 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, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1245-1263. doi: 10.1016/j.jacc.2023.06.043.

  PMID: 37704315 BACKGROUND

• 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. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25.

  PMID: 30266608 BACKGROUND

MeSH Terms

Conditions

Angina Pectoris, Variant

Condition Hierarchy (Ancestors)

Angina, Unstable; Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Rafael Mila, MD

CONTACT

+59824871515; r1000a@gmail.com

Victor Dayan, MD, PhD

CONTACT

+5989924871515; victordayan24@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Cardiology and Head of Interventional Cardiology

Model Details: All participants will undergo the same structured diagnostic and therapeutic pathway. The intervention consists of invasive coronary phenotyping followed by individualized treatment according to the functional and/or morphological mechanism identified. There is no randomization and no comparator arm.

Study Record Dates

• First Submitted: May 10, 2026
• First Posted: May 18, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: May 18, 2026

Record last verified: 2026-05

Locations

UR (1)