Inflammation-mediated Coronary Plaque Vulnerability, Myocardial Viability and Ventricular Remodeling (VIABILITY)

• ClinicalTrials.gov Identifier: NCT03830944
• Recruitment Status: Unknown
• First Posted: February 5, 2019
• Last Update Posted: July 26, 2019
• Sponsor: Cardio Med Medical Center
• Collaborators: George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures; Tîrgu Mureș Emergency Clinical County Hospital, Romania
• Information provided by (Responsible Party): Cardio Med Medical Center

Study Description

Brief Summary:

VIABILITY study aims to investigate the link between systemic inflammation, pancoronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). The level of systemic inflammation in the acute phase of the myocardial infarction and at 1 month will be assessed on the basis of serum levels of inflammatory biomarkers (hsCRP, matrix metalloproteinases, interleukin-6). Pancoronary plaque vulnerability will be assessed: (1) in the acute phase of the infarction, based on serum biomarkers known to be associated with increased plaque vulnerability, such as adhesion molecules (V-CAM or I-CAM) determined from the blood samples collected in the first day after STEMI; (2) at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features present in all coronary plaques. Myocardial viability and remodeling will be assessed based on: (1) 3D speckle tracking echocardiography associated with dobutamine infusion; (2) MRI imaging associated with complex post-processing techniques for mapping myocardial fibrosis and scar at the level of left atrium and left ventricle. At the same time, CT imaging features associated with systemic and local inflammation, such as global epicardial fat or local pericoronary epicardial fat will be quantified in order to investigate the impact of inflammatory-mediated plaque vulnerability on the extent of myocardial damage in acute myocardial infarction. All these parameters will be investigated in patients with successful primary revascularization performed in a timely manner for ST-segment elevation acute myocardial infarction, who will be divided into 2 groups: group 1 - patients who present persistence of an augmented inflammatory status defined as serum levels of hsCRP>3.0 mg/dl at discharge from the hospital or at 7 days postinfarction (whichever comes first), and group 2 - patients with no persistence of augmented inflammatory status (hsCRP<3.0 mg/dl).

The primary endpoint of the study will be represented by the rate of post-infarction heart failure development, defined as the rate of re-admission in the hospital for heart failure or by a significant decrease in the ejection fraction (<45%).

The secondary endpoints of the study will be:

• rate of re-hospitalization
• rate of repeated revascularization
• rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke)

Condition or disease	Intervention/treatment
Acute Myocardial Infarction; Heart Failure	Diagnostic Test: Blood sampling; Diagnostic Test: transthoracic echocardiography; Diagnostic Test: Late Gadolinium-Enhancement Cardiac Magnetic Resonance; Diagnostic Test: Coronary Angio Computed Tomography

Detailed Description:

Patients with acute myocardial infarction (AMI) who survive the acute event, very often present a significant deterioration of their clinical status with progression towards heart failure, which is directly linked to the extent of myocardial injury and the remodeling process starting immediately after infarction. The major aim of the urgent revascularization in STEMI is to save myocardial tissue from death and necrosis, in order to recover viable myocardium. It is well-known that one of the major factors that trigger an AMI is the systemic inflammation, which has a direct influence on coronary plaque vulnerability. At the same time, 20% of patients surviving an AMI present a recurrent cardiovascular event in the following 12 months, as a result of increased systemic inflammation triggered by the infarction, which leads to vulnerabilization of other atheromatous plaques from all the circulatory system in the post-infarction period. While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree on the extension of ventricular remodeling and scaring has not been elucidated so far.

This is a clinical prospective, descriptive, single-center study which will be carried out in the University of Medicine, Pharmacy, Science and Technology Tîrgu Mures, Romania, in collaboration with two clinical sites: Center of Advanced Research in Multimodal Cardiac Imaging Cardio Med Tîrgu Mures, Romania and County Clinical Emergency Hospital Tîrgu Mures, Romania. The duration of the study is 2 years which includes the initial screening and the follow-up period.

The study will enroll 100 subjects with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms. Imaging biomarkers and laboratory analyses such as: high sensitive C Reactive Protein (hsCRP), matrix metalloproteinases (MMP), interleukin-6 (IL6) and N-Terminal Pro-B-Type Natriuretic Peptide (NT pro-BNP) will be determined in the first 24 hours after the index hospitalization. At 1 month postinfarction all patients will undergo Dobutamine stress test associated with speckle tracking echocardiography for evaluation of myocardial function and viability, CMR for assessment of myocardial scar, function and remodeling, and Multislice Angio CT for assessment of pancoronary vulnerability, by complex characterization of vulnerability features in all the coronary plaques present in the coronary tree. All these parameters will be investigated in patients with successful primary percutaneous coronary revascularization, who will be divided into 2 groups: group 1 -patients with persistent elevation of systemic inflammatory biomarkers at discharge from the hospital or at day 7 (whichever comes first) (inflammation+ group); and group 2 - patients with no persistent elevation of systemic inflammatory biomarkers at discharge from the hospital or at day 7 (whichever comes first) (inflammation- group). In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers, adhesion molecules and NT-proBNP at 24 hours and 7 days post procedure, the amount of myocardial fibrosis and scar in the left ventricle at 1 month, the degree of ventricular remodeling and myocardial perfusion at 1 month and the amount of epicardial fat surrounding the heart and the plaques. The study will be conducted over a period of 2 years, in which patients will be examined at baseline, and will be followed-up for MACE incidence.

All patients will sign an informed written consent and will be checked for the exclusion criteria prior to enrollment.

Study objectives:

Primary: To investigate the link between coronary inflammation-mediated plaque vulnerability, myocardial viability and ventricular remodeling in the post-infarction period.

Secondary:

• To investigate the impact of systemic inflammation on structural remodeling of the left ventricle in the post-infarction period
• To investigate the impact of local inflammatory response on pancoronary plaque vulnerability following an acute myocardial infarction.

Study Timeline:

• Baseline - visit 1 (day 0)
• Obtain and document consent from participant on study consent form.
• Verify inclusion/exclusion criteria.
• Obtain demographic information, medical history, medication history, alcohol and tobacco use history.
• Record results of physical examinations and 12-lead ECG.
• Collect blood specimens (complete blood count, biochemistry, inflammatory biomarkers, acute adhesion molecules).
• Imaging procedures: transthoracic 2-D echocardiography/speckle tracking
• Visit 2 (day 7 / discharge from the hospital)
• -hsCRP
• Visit 3 (month 1)
• Coronary Computed Tomographic Angiography (vulnerability features, epicardial fat, myocardial perfusion)
• Cardiac Magnetic Resonance (myocardial fibrosis/scar, remodeling, viability)
• Dobutamine stress echocardiography / speckle tracking (viability)
• Visit 4,5,6 (month 3,6,9)
• Record results of physical examinations, 12-lead ECG and medical history.
• Imaging procedures: transthoracic 2-D echocardiography
• Final study visit (month 12)
• Record results of physical examinations, medical history,12-lead ECG
• Imaging procedures: transthoracic 2-D echocardiography
• End-point evaluation.

Study procedures:

• Medical history, clinical examination, laboratory tests (complete blood count, biochemistry, serum level of hs-CRP, MMP, IL6, NT-pro-BNP, adhesion molecules);
• 12-lead ECG
• 2D transthoracic echocardiography with measurement of: cardiac diameters, volumes, left ventricular systolic and diastolic function, speckle tracking echo, dobutamine viability test.
• Late Gadolinium-Enhancement Cardiac Magnetic Resonance (LGE-CMR) with the evaluation of myocardial scar and fibrosis, ventricular function and remodeling index.
• Angio Computed Tomography with assessment of coronary plaque vulnerability (based on vulnerability features: positive remodeling, spotty calcification, napkin-ring sign, low density plaque) and myocardial perfusion Data collection: All the information will be collected in a database that consists of patient's background, medical history, medication, imaging features provided by cardiac ultrasound, Cardiac magnetic resonance, Angio CT and imaging post-processing data.

Study Design

• Study Type: Observational
• Estimated Enrollment: 100 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Impact of Inflammation-mediated Response on Pan-coronary Plaque Vulnerability, Myocardial Viability and Ventricular Remodeling in the Post-infarction Period - the VIABILITY Study
• Actual Study Start Date: July 25, 2019
• Estimated Primary Completion Date: March 1, 2021
• Estimated Study Completion Date: March 1, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
G1; Study subjects with STEMI and increased inflammatory response at 7 days after STEMI Interventions: Blood sampling; transthoracic echocardiography; Late Gadolinium-Enhancement Cardiac Magnetic Resonance; Coronary Angio Computed Tomography	Diagnostic Test: Blood sampling; Assessment of complete blood count, biochemistry, inflammatory biomarkers, adhesion molecules; Diagnostic Test: transthoracic echocardiography; Assessment of the ventricular anatomy, size, function, speckle tracking, myocardial strain, valvular function.; Diagnostic Test: Late Gadolinium-Enhancement Cardiac Magnetic Resonance; Assessment of the ventricular anatomy, function, viability, degree of fibrosis, quantification of infarct size, mass.; Diagnostic Test: Coronary Angio Computed Tomography; Assessment of coronary plaque anatomy, morphology, vulnerability features, quantification of epicardial adipose tissue
G2; Study subjects with STEMI and no increased inflammatory response at 7 days after STEMI Interventions: Blood sampling; transthoracic echocardiography; Late Gadolinium-Enhancement Cardiac Magnetic Resonance; Coronary Angio Computed Tomography	Diagnostic Test: Blood sampling; Assessment of complete blood count, biochemistry, inflammatory biomarkers, adhesion molecules; Diagnostic Test: transthoracic echocardiography; Assessment of the ventricular anatomy, size, function, speckle tracking, myocardial strain, valvular function.; Diagnostic Test: Late Gadolinium-Enhancement Cardiac Magnetic Resonance; Assessment of the ventricular anatomy, function, viability, degree of fibrosis, quantification of infarct size, mass.; Diagnostic Test: Coronary Angio Computed Tomography; Assessment of coronary plaque anatomy, morphology, vulnerability features, quantification of epicardial adipose tissue

Outcome Measures

Primary Outcome Measures :

1. Rate of post-infarction heart failure [ Time Frame: 12 months ]
   The primary outcome measure will be represented by the rate of post-infarction heart failure development, defined as the rate of re-admission in the hospital for heart failure or by a significant decrease in the ejection fraction (<45%).

Secondary Outcome Measures :

1. Rate of re-hospitalization [ Time Frame: 12 months ]
   Re-hospitalization for cardiovascular related causes
2. Rate of repeated revascularization [ Time Frame: 12 months ]
   Repeated myocardial revascularization procedures
3. Rate of major adverse cardiovascular events [ Time Frame: 12 months ]
   Occurrence of major adverse cardiovascular events described as cardiovascular death, stroke.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Study population includes patients from a single center with STEMI meeting inclusion and exclusion criteria and undergoing primary PCI.

Criteria

Inclusion Criteria:

• Patients with ST-segment elevation acute myocardial infarction treated by primary PCI within the first 12 hours after the onset of symptoms
• Ability to provide informed consent;
• Patients aged at least 18 years;

Exclusion Criteria:

• Patients with acute coronary syndrome in the last 30 days
• Unwillingness or incapacity to provide informed consent;
• Allergy to contrast media;
• Absolute or relative contraindications to magnetic resonance imaging
• Pregnancy or lactation;
• Women with childbearing potential in absence of any contraceptive treatment
• Renal insufficiency (creatinine greater than 1.5 mg/dL) or renal failure requiring dialysis;
• Active malignancy or malignancy within the last 5 year prior to enrollment;
• Conditions associated with an estimated life expectancy of under 1 year;

Contacts and Locations

Contacts

Contact: Mirabela Morariu, MD; +40 740651897; mirabela.morariu@yahoo.com

Contact: Theodora Benedek, Professor; +40722560549; theodora.benedek@gmail.com

Locations

Romania

Cardio Med Medical Center; Recruiting

Targu Mures, Mures, Romania, 540102

Contact: Theodora Benedek, Professor

Sponsors and Collaborators

Cardio Med Medical Center

George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures

Tîrgu Mureș Emergency Clinical County Hospital, Romania

Investigators

• Principal Investigator: Mirabela Morariu, MD; University of Medicine, Pharmacy, Science and Technology of Tîrgu Mures, Romania

More Information

• Responsible Party: Cardio Med Medical Center
• ClinicalTrials.gov Identifier: NCT03830944
• Other Study ID Numbers: CM0119-VIA
• First Posted: February 5, 2019
• Last Update Posted: July 26, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication will be available for interested parties.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: The IPD sharing frame is starting 6 months after publication.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cardio Med Medical Center:

ST elevation myocardial infarction; Inflammatory Response; Coronary plaque vulnerability; myocardial viability

Additional relevant MeSH terms:

Myocardial Infarction; Inflammation; Infarction; Ventricular Remodeling; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemia; Necrosis; Myocardial Ischemia; Vascular Diseases; Pathological Conditions, Anatomical