Identification of Molecular Mechanisms of Coronary Instability in Homogeneous Subsets of Patients With Acute Coronary Syndromes for the Implementation of Precision Medicine (PRECISION)

Identification of Molecular Mechanisms of Coronary Instability in Homogeneous Subsets of Patients With Acute Coronary Syndromes for the Implementation of Precision Medicine (PRECISION Study)

To further improve the outcome of ACS it is strongly needed to identify new therapeutic targets. This is possible only by improving our knowledge of the multiple molecular mechanisms leading to coronary instability through several pathways. The goal of this project is to define the molecular mechanisms responsible for the four different presentations of ACS, to identify biomarkers for their noninvasive identification and potential new therapeutic targets, thus promoting precision medicine.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome; Chronic Coronary Syndrome
• Intervention / Treatment: Diagnostic test: Venous blood samples, Biological samples analysis, Cardiology visit.

Detailed Description

This is a multicenter prospective observational study, involving 5 Research Units (RU), the enrollment-phase will take 18 months (month 6 to 24). This is an explorative project that will prospectively enroll: 1) Consecutive patients with an admission diagnosis of ACS with Non ST elevation myocardial infarction (NSTEMI) confirmed at coronary angiography, undergoing OCT evaluation of the culprit coronary plaque before stent implantation for clinical reasons and with a clearly identifiable feature of the culprit plaques according to current European guidelines. ECG changes may include transient ST- segment elevation, persistent or transient ST-segment depression, T-wave inversion, flat T waves or pseudo- normalization of T waves or the ECG may be normal. Taking into account our previous studies, the investigators estimated that between 30-35% of NSTEMI patients will undergo OCT evaluation; 2) Consecutive patients with symptoms of Stable Angina (SA) lasting >12 months, angiographically confirmed coronary artery disease, without any episode suggestive of previous acute event, and no overt ischemic episodes during the last 48 hours, according to current European guidelines. Myocardial ischemia was documented by afunctional test (ie, exercise treadmill testing and/or myocardial perfusion imaging). Patients showing Q waves on 12-lead electrocardiogram and/or abnormal echocardiogram (ie, left ventricular ejection fraction <40% and/or wall motion abnormalities) were excluded. NSTEMI (within 12 hours of symptom onset) and SA patients will be enrolled at the time of their admission to the Coronary Care Unit and to the SubIntensive Cardiac Care Unit, of wich Prof. Giovanna Liuzzo (project PI) is the supervising physician; 3) In the same period, consecutive Mitral Valve Disease patients (MVD) with angiographically normal coronary arteries undergoing surgery for mitral valve regurgitation, age and sex matched 1:3 with NSTEMI patients, will be enrolled as control group. MVD patients will be enrolled at Cardiosurgery Operative Unit, lead by Professor Massimo Massetti.

Our RU1 will enroll:

1. 150 consecutive patients with an admission diagnosis of NSTEMI.
2. 50 consecutive patients with a diagnosis of SA.
3. 50 consecutive MVD.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Giovanna GL Liuzzo; Phone Number: 06/30154187; Email: giovanna.liuzzo@policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy, 00168
    • Active, not recruiting
    • Fondazione Policlinico Gemelli
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

1. Patients with plaque rupture and inflammation;
2. Patients with plaque rupture without inflammation;
3. Patients with intact fibrous plaque with evidence of thrombus (plaque erosion);
4. Patients with a smooth plaque.

Description

Inclusion Criteria:

• Men and post-menopause women of age 45-80 years; ability to understand and sign the informed consent;
• For NSTEMI and SA patients inclusion criteria will include evidence of obstructive atherosclerosis (> 70% stenosis) at invasive coronary angiography;

Exclusion Criteria:

• Evidence of inflammatory or infectious diseases, malignancies, immunological or haematological disorders;
• Ejection fraction less than 40%;
• Treatment with anti-inflammatory drugs other than low-dose aspirin, and with antibiotic therapies until 1 month before the enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NSTEMI patients; Patients no ST-segment elevation myocardial infarction (NSTEMI)	Diagnostic test: Venous blood samples, Biological samples analysis, Cardiology visit.; These interventions are important to study all patients recruited
SA patients; Patients with Stable Angina (SA) diagnosis	Diagnostic test: Venous blood samples, Biological samples analysis, Cardiology visit.; These interventions are important to study all patients recruited
MVD patients; Patients with consecutive Mitral Valve Disease patients (MVD)	Diagnostic test: Venous blood samples, Biological samples analysis, Cardiology visit.; These interventions are important to study all patients recruited

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify homogeneous subsets of ACS patients at OCT interrogation of the culprit plaque	Using Optical Coherence Tomography	2 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the role of shear stress in coronary instability	On OCT-based reconstruction of coronary lesions and fluid dynamics studies;	1 year
Establish the most efficient and cost-effective biomarker panel	Establish the most efficient and cost-effective biomarker panel for the identification of homogeneous ACS patient subsets, this approach is relevant especially in centers where OCT is not available and unravel specific mechanisms and players of coronary instability and to identify molecular therapeutic targets, taking advantage of newomics technologies.	1 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 13, 2019
• Primary Completion (ANTICIPATED): September 5, 2023
• Study Completion (ANTICIPATED): September 13, 2024

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (ESTIMATE): February 14, 2023

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Atherosclerotic plaque; Optical Coherence Tomography
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: 2747

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No