BIOmarkers and PLAtelet Function Assessment in Myocardial Ischemia and Non Obstructive Coronary Arteries Study

NCT05714241 | Recruiting

• 1 other identifier: 4657
• Study Type: observational
• Target: 200
• Locations: 2 countries
• Sites: 2

Brief Summary

Ischemia with non-obstructive coronary artery disease (INOCA) identifies a significant proportion of patients presenting with signs and symptoms of myocardial ischemia with normal or near-normal coronary arteries at angiography. Initially believed a benign condition, it is now well-established that INOCA is associated with an increased risk for cardiovascular events. However, it is rarely correctly diagnosed. The identification of distinct signatures of circulating biomarkers and platelet alterations associated with the specific endotype of INOCA (Microvascular Angina \[MVA\]; Vasospastic Angina \[VSA\]; both MVA and VSA; and none) may help in the diagnosis of these patients as well as in the identification of specific pathophysiologic pathways and the development of future therapies. In addition, the identification of specific signatures may help in the prognostic stratification of INOCA patients, identifying those that may need more aggressive therapy and closer follow-up. Finally, the results deriving from this study may pave the way for a new pathophysiology-driven approach with cause-target therapies personalized for the specific mechanisms of INOCA. The BIOPLATINO study is the first study specifically designed to evaluate if there is a unique signature of circulating biomarkers and/or platelet function tests able to discriminate between the multiple pathogenetic mechanisms of INOCA as well as the different clinical courses. Furthermore, it may pave the way for the identification of specific pathophysiologic pathways of INOCA and the development of future therapies.

Conditions

Ischemia With no Obstructive Coronary Artery Disease

Keywords

INOCA

Outcome Measures

Primary Outcomes (1)

• Biomarker, miRNA and platelet function assessment for the specific endotype of INOCA

  Serum levels of circulating biomarkers, miRNAs and the results of platelet function tests as well as their combinations will be analyzed to evaluate sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the specific endotype of INOCA (MVA, VSA, both MVA and VSA, or none).

  Up to 30 days

Secondary Outcomes (2)

• Biomarker, miRNA and platelet function assessment at 1 year follow up

  1 year

• Assessment of prediction model of future cardiovascular events (MACE) at 1-year follow-up.

  1 year

Study Arms (1)

Ischemia with non-obstructive coronary artery disease

Patients with INOCA will be defined as those presenting with either stable, chronic symptoms (stable angina or angina equivalent) and/or signs of ischemia on noninvasive testing (i.e.: exercise stress test, stress echocardiography or nuclear imaging) undergoing elective diagnostic CAG and without obstructive coronary artery disease (defined as \<50% diameter stenosis and/or fractional flow reserve \[FFR\]\>0.80 in any major epicardial vessel).

Other: Data extraction; Other: Blood sampling; Other: Clinical Follow-up

Interventions

Data extraction OTHER

After routine coronary function testing using a diagnostic pressure-temperature sensor guidewire in order to assess Coronary Flow Reserve (CFR) and the Index of Microvascular Resistance (IMR); and/or the acetylcholine (Ach) provocative test to assess the presence of coronary vasomotion disorders, patients will be stratified, accordingly to coronary function testing and Ach provocative test, in four groups/endotypes: 1. MVA (evidence of CMD defined as any of abnormal CFR \[\<2.0\], IMR \[≥25\], or microvascular spasm); 2. VSA (CFR ≥2.0, IMR \<25 and epicardial spasm); 3. both MVA and VSA (evidence of CMD and epicardial spasm); 4. none/non-cardiac chest pain (CFR ≥2.0 and IMR \<25 and neither microvascular nor epicardial spasm).

Ischemia with non-obstructive coronary artery disease

Blood sampling OTHER

At the time of this coronary angiography, arterial blood samples through the radial sheath will be collected. If collected at the time of any follow-up visit, venous blood samples will be collected by venipuncture with the same modalities to obtain whole blood, serum and plasma samples after centrifugation.

Ischemia with non-obstructive coronary artery disease

Clinical Follow-up OTHER

All patients will undergo a final follow-up visit at 12 months from the date of enrollment. During the visit, the incidence of MACE in the past months will be investigated, the Seattle Angina Questionnaire (SAQ) will be administered and the SAQ summary score will be collected.

Ischemia with non-obstructive coronary artery disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with INOCA will be defined as those presenting with either stable, chronic symptoms (stable angina or angina equivalent) and/or signs of ischemia on noninvasive testing (i.e.: exercise stress test, stress echocardiography or nuclear imaging) undergoing elective diagnostic CAG and without obstructive coronary artery disease (defined as \<50% diameter stenosis and/or fractional flow reserve \[FFR\]\>0.80 in any major epicardial vessel).

You may qualify if:

• Patients aged ≥ 18 years
• Patients diagnosed with INOCA
• Patients in therapy with acetylsalicylic acid (100 mg/die per os for more than 3 days or 250 mg intravenous in the past 3 days followed by 100 mg/die per os).

You may not qualify if:

• the use of thrombolytics, platelet glycoprotein (GP) IIb/IIIa blockers, oral anticoagulants, thienopyridine pretreatment, platelet counts outside the range of 125-450 10 9/l.
• comorbidities with an expected survival less than 1 year and contraindication to drugs administrated (e.g.: history of hypersensitivity to drugs administrated or its excipients, significant renal and/or hepatic disease).

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (2)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Hospital Clínic Cardiovascular Institute

Barcelona, Spain

RECRUITING

Related Publications (20)

• GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1736-1788. doi: 10.1016/S0140-6736(18)32203-7. Epub 2018 Nov 8.

  PMID: 30496103 BACKGROUND

• Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of Ischemic Heart Disease. Circulation. 2018 Oct 2;138(14):1463-1480. doi: 10.1161/CIRCULATIONAHA.118.031373.

  PMID: 30354347 BACKGROUND

• Reeh J, Therming CB, Heitmann M, Hojberg S, Sorum C, Bech J, Husum D, Dominguez H, Sehestedt T, Hermann T, Hansen KW, Simonsen L, Galatius S, Prescott E. Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina. Eur Heart J. 2019 May 7;40(18):1426-1435. doi: 10.1093/eurheartj/ehy806.

  PMID: 30561616 BACKGROUND

• Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, Jorgensen E, Kelbaek H, Prescott E. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012 Mar;33(6):734-44. doi: 10.1093/eurheartj/ehr331. Epub 2011 Sep 11.

  PMID: 21911339 BACKGROUND

• Jespersen L, Abildstrom SZ, Hvelplund A, Prescott E. Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013 Aug;102(8):571-81. doi: 10.1007/s00392-013-0568-z. Epub 2013 May 1.

  PMID: 23636227 BACKGROUND

• Taqueti VR, Solomon SD, Shah AM, Desai AS, Groarke JD, Osborne MT, Hainer J, Bibbo CF, Dorbala S, Blankstein R, Di Carli MF. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018 Mar 7;39(10):840-849. doi: 10.1093/eurheartj/ehx721.

  PMID: 29293969 BACKGROUND

• Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.

  PMID: 32626906 BACKGROUND

• Ford TJ, Ong P, Sechtem U, Beltrame J, Camici PG, Crea F, Kaski JC, Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C; COVADIS Study Group. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When. JACC Cardiovasc Interv. 2020 Aug 24;13(16):1847-1864. doi: 10.1016/j.jcin.2020.05.052.

  PMID: 32819476 BACKGROUND

• Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. doi: 10.1056/NEJMra061889. No abstract available.

  PMID: 17314342 BACKGROUND

• Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: an update. Eur Heart J. 2014 May;35(17):1101-11. doi: 10.1093/eurheartj/eht513. Epub 2013 Dec 23.

  PMID: 24366916 BACKGROUND

• Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ, Niccoli G, Crea F. Coronary Microvascular Dysfunction Across the Spectrum of Cardiovascular Diseases: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 28;78(13):1352-1371. doi: 10.1016/j.jacc.2021.07.042.

  PMID: 34556322 BACKGROUND

• Maseri A. Louis F. Bishop lecture. Role of coronary artery spasm in symptomatic and silent myocardial ischemia. J Am Coll Cardiol. 1987 Feb;9(2):249-62. doi: 10.1016/s0735-1097(87)80372-8.

  PMID: 3543091 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

• Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11.

  PMID: 31709984 BACKGROUND

• Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation. 2017 Mar 14;135(11):1075-1092. doi: 10.1161/CIRCULATIONAHA.116.024534.

  PMID: 28289007 BACKGROUND

• Gurbel PA, Bliden KP, Hayes KM, Tantry U. Platelet activation in myocardial ischemic syndromes. Expert Rev Cardiovasc Ther. 2004 Jul;2(4):535-45. doi: 10.1586/14779072.2.4.535.

  PMID: 15225113 BACKGROUND

• Choi JL, Li S, Han JY. Platelet function tests: a review of progresses in clinical application. Biomed Res Int. 2014;2014:456569. doi: 10.1155/2014/456569. Epub 2014 May 8.

  PMID: 24895576 BACKGROUND

• Lanza GA, Andreotti F, Sestito A, Sciahbasi A, Crea F, Maseri A. Platelet aggregability in cardiac syndrome X. Eur Heart J. 2001 Oct;22(20):1924-30. doi: 10.1053/euhj.2001.2624.

  PMID: 11601836 BACKGROUND

• Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014 Sep;7(5):640-7. doi: 10.1161/CIRCOUTCOMES.114.000967. Epub 2014 Sep 2.

  PMID: 25185249 BACKGROUND

• Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.

  PMID: 31504439 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, plasma, platelet, peripheral blood mononuclear cells

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rocco A Montone, MD, PhD

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rocco A Montone, MD, PhD

CONTACT

+39-0630154187; roccoantonio.montone@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: IRCCS Researcher

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 6, 2023
• Study Start: February 1, 2022
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); ES (1)