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

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.