Systemic, Pancoronary and Local Coronary Vulnerability
Systemic, Pancoronary and Local Coronary Vulnerability
• The aim of the VIP study is to investigate the impact of vulnerability markers
 (inflammatory serum biomarkers for systemic vulnerability, coronary shear stress and
 vulnerability mapping for pancoronary vulnerability, and imaging-based plaque features for
 systemic vulnerability) on the rate of major adverse cardiovascular events caused by
 progression of the non-culprit lesion in patients with acute ST or non-ST segment elevation
 myocardial infarction who undergo revascularization of the culprit lesion during the acute
 event. Furthermore, the study will evaluate the rate of progression of non-culprit lesions
 towards a higher degree of vulnerability, based on coronary computed tomography angiographic
 assessment at 1 year after enrollment.
The project is a prospective, cohort, mono-centric study which will be carried out in the
 Center of Advanced Research in Multimodal Cardiac Imaging Cardiomed.

 The project will include 100 subjects who present ST and non-ST segment elevation myocardial
 infarction at 30 days prior to study enrollment, who underwent emergency revascularization of
 the culprit lesion. Samples for systemic serum biomarkers for myocardial injury, myocardial
 strain and enhanced systemic inflammation will be collected at the moment of the acute event.
 All patients will undergo coronary CT angiography, cardiac perfusion CT and intracoronary
 imaging procedures (Intravascular ultrasound - IVUS; Optical Coherence Tomography - OCT) at
 the moment of enrollment in the study, for complex assessment of non-culprit coronary
 lesions. The endothelial coronary shear stress will be calculated with imaging
 post-processing techniques on the CT data acquired at baseline, by using computational fluid
 dynamics.

 The study will be conducted over a period of 3 years, in which patients will be examined at
 baseline, and during several follow-up visits. At the one-year follow-up, the study subjects
 will undergo CT coronary angiography for re-evaluation of the non-culprit lesions, in the
 prospects of analyzing the rate of plaque progression towards a higher degree of
 vulnerability. At the end of the 3-year period, patients will be assessed about the
 occurrence of major adverse cardiovascular events and the rate or revascularization for
 non-culprit lesions.

 Study objectives:

 Primary: to investigate the association between systemic, pancoronary and local vulnerability
 features of coronary plaques and the risk for major adverse cardiac events - MACE (all-cause
 mortality, cardiovascular death, myocardial infarction, repeated revascularization, repeated
 hospitalizations for cardiovascular related incidents, cerebrovascular events) during a
 3-year follow-up.

 Secondary: to assess the rate of progression for the non-culprit lesions towards a higher
 degree of vulnerability, as evaluated via coronary CT angiography at 1 year after enrollment,
 in relation to systemic, pancoronary and local vulnerability features at baseline.

 To identify the type of vulnerability (systemic, pancoronary or local) with the highest
 impact on plaque progression and future MACE

 Study Timeline:

 Baseline (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.

 -  Imaging procedures: transthoracic 2-D echocardiography, 128-multisclice CT angiography,
 cardiac perfusion CT, IVUS, OCT

 Visit 1 (month 1)

 -  Record results of physical examinations, 12-lead ECG and medical history.

 -  Imaging procedures: transthoracic 2-D echocardiography

 Visit 2 (month 3)

 • Telephone follow-up

 Visit 3 (month 6)

 -  Record results of physical examinations, 12-lead ECG and medical history.

 -  Imaging procedures: transthoracic 2-D echocardiography

 Visit 4 (month 12)

 -  Record results of physical examinations, 12-lead ECG and medical history.

 -  Imaging procedures: transthoracic 2-D echocardiography, 128-multislice CT coronary
 angiography for evaluation of non-culprit lesion

 -  End-point evaluation

 Visit 5 (month 15)

 • Telephone follow-up

 Visit 6 (month 18)

 • Telephone follow-up

 Visit 7 (month 24)

 -  Record results of physical examinations, 12-lead ECG and medical history.

 -  Imaging procedures: transthoracic 2-D echocardiography.

 -  End-point evaluation

 Visit 8 (month 30)

 • Telephone follow-up

 Final study visit (month 36)

 -  Record results of physical examinations, 12-lead ECG and medical history.

 -  Imaging procedures: transthoracic 2-D echocardiography

 -  End-point evaluation.

 Study procedures:

 -  Clinical examination, medical history

 -  12-lead ECG

 -  2D transthoracic echocardiography with measurement of: cardiac diameters, volumes,
 valvular function and regurgitation, pressure gradients, pericardial fat thickness,
 pericardial effusion, left ventricular global and regional function and ejection
 fraction.

 -  128-multislice CT coronary angiography with the evaluation of: epicardial fat volume,
 plaque burden, total and local calcium score, markers for lesion severity (degree of
 stenosis, lesion length, lumen area and diameter, minimum and maximum plaque thickness);
 morphological plaque characteristics (plaque related volumes, plaque burden, vascular
 indexes - remodeling and eccentricity index); plaque components evaluated via volumetric
 and planimetric units (necrotic core, fibrofatty tissue, fibrotic tissue, dense
 calcium); markers of plaque vulnerability (necrotic core, low attenuation plaque, spotty
 calcification, napkin ring sign, positive remodeling).

 -  Shear stress evaluation of CT acquired images and computational fluid dynamics

 -  Intracoronary imaging techniques: IVUS and OCT with evaluation of plaque
 characteristics.

 -  Venous blood sample collection during the acute coronary event for evaluation of serum
 levels of hsCRP, IL-6, matrixmetalloproteases MMP9, Adhesion molecules (VCAM, ICAM),
 alfa tumour necrosis factor, hs-cTnI, NTproBNP

 Data collection: In a dedicated database that includes all patient information, demographics,
 medical history, medication, therapeutic procedures, information derived from imaging
 techniques (echocardiography, CT angiography, CT imaging post-processing and shear stress
 evaluation).
Inclusion Criteria:

 -  Patients aged over 18 years old that have signed the written informed consent;

 -  Patients with ST and non-ST segment elevation myocardial infarction (as stated in the
 Third Universal Definition of Myocardial Infarction) at 30 days prior to
 randomization;

 Exclusion Criteria:

 -  unwillingness or incapacity to provide informed consent (and if consent of legal
 guardian or family is not available);

 -  acute myocardial infarction at the moment of randomization (as these patients are
 referred to the hospital for emergency invasive coronary angiography and
 revascularization)

 -  conditions that present an estimated life expectancy of under 5 years;

 -  acute renal failure or terminal stage chronic kidney disease;

 -  pregnancy or lactation and women of reproductive age who are not using any
 contraceptive method;

 -  allergy and history of allergic reactions to iodine contrast media;

 -  active malignancy or malignancy within the last 1 year prior to enrollment;

 -  patients who, in the opinion of the investigators are not compliant and will not
 present for study visits.