Clinical trial NCT05488249: CCTA Coronary Hemodynamics, Systemic Inflammation and Vulnerable Plaques (COHESIVE)
Official title: CCTA Study of Atheromatous Lesions, Coronary Hemodynamics and Systemic Inflammation in Patients With Vulnerable Plaques (COHESIVE STUDY)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Systemic Inflammatory Response
Chronic Coronary Syndrome
Atherosclerosis
Keywords: coronary vulnerable plaque
CCTA
Systemic inflammation
Coronary shear stress
Plaque topography
Lead sponsor: Cardio Med Medical Center
Sponsor class: INDUSTRY
Collaborators: name: George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures
name: University Hospital of Targu Mures, Romania
First posted: 2022-08-04
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stable chest pain who present in out-patient conditions for complete clinical assessment and CCTA evaluation of coronary artery tree, without any history of coronary revascularization, with a low to intermediate pre-test probability for coronary artery disease, who do not present acute or chronic inflammatory/infections disease or malignancy that could interfere with the systemic inflammatory response.

Brief summary: Although there are numerous studies that have demonstrated the impact of systemic inflammation on coronary plaque vulnerability, there are few literature data regarding the influence of coronary plaque localization within the coronary tree (right and left coronary artery, proximal, mid-coronary and distal), on plaque composition, morphology and degree of vulnerability, in relation with systemic inflammation and coronary hemodynamics. The aim of this study is to identify: (1) the impact of plaque topography in different sites within the coronary tree (right versus left, proximal distal) on their vulnerability degree evaluated with CCTA; (2) the relationship between degree of plaque vulnerability, systemic inflammatory biomarkers and specific hemodynamic characteristics quantified by coronary shear stress computations. The study will include 100 patients with stable coronary artery disease for which data collection will be perform on: (1) Clinical, echocardiographic and ECG data; (2) cardiovascular risk assessment; (3) 128 slice CCTA evaluation of coronary tree anatomy, plaque morphology, composition and vulnerability degree; (4) systemic inflammation based on serum levels of hsCRP, IL-6, MMP-9, periostin, adhesion molecules (5) shear stress via coronary flow computational simulations.

Detailed description: This is a clinical, observational cross sectional, mono-centric study which will be carried out in the Center of Advanced Research in Multimodal Cardiac Imaging Cardiomed in collaboration with the University of Medicine, Pharmacy, Sciences and Technology "GE Palade".

The project will include 100 subjects with stable coronary artery disease (defined according to the ESC guidelines for management of patients with chronic coronary syndromes), presenting in out-patient conditions, who will undergo 128 slice CCTA evaluation of coronary artery tree anatomy, coronary plaque morphology, composition and degree of vulnerability.

Samples for systemic serum biomarkers for systemic inflammation will be collected at the moment of CCTA image acquisition for all patients. 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 6 months, in which patients will be examined for clinical data, echocardiography assessment of left ventricular function, valvular disease, diastolic function, 12-lead ECG, cardiovascular risk assessment, systemic inflammation (based on serum levels of hsCRP, interleukin-6, MMP-9, periostin, adhesion molecules. Coronary plaque analysis will be conducted on an offline station by using dedicated post-processing software for detection of plaque morphology (length, volume, degree of stenosis, plaque location within the coronary tree, remodeling and eccentricity index), composition (lipid rich, fibrotic and calcified volumes), degree of vulnerability (identification of positive remodeling, low attenuation, spotty calcium, napkin ring sing). After plaque selection and analysis, computational fluid dynamics based on CCTA images will be performed on an offline dedicated station for coronary shear stress quantification.

Primary exclusion criteria include acute coronary syndromes at the moment of enrollment, with myocardial necrosis, the presence of coronary stents and extensive calcifications and suboptimal CCTA image acquisition that could interfere with plaque analysis, as well as contraindications for administration of contrast media agent (renal disease, allergies, thyroid dysfunction).

Study objectives:

Primary: to investigate the association between coronary plaque topography in different sites within the coronary tree (right versus left, proximal distal) and their vulnerability degree evaluated with CCTA.

Secondary: to assess the relationship between degree of plaque vulnerability, systemic inflammatory biomarkers and specific hemodynamic characteristics quantified by coronary shear stress computations in relation to plaque location.

Study procedures

* Clinical examination, medical history, cardiovascular risk assessment
* 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
* Venous blood sample collection during the acute coronary event for evaluation of serum levels of hsCRP, IL-6, matrix metalloproteases - MMP9, Adhesion molecules (VCAM, ICAM, e-selectin, p-selectin), periostin.
* 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).

Eligibility criteria: Inclusion Criteria:

* chronic coronary syndromes (defined according to current ESC guidelines) presenting in out-patient conditions for CCTA evaluation of stable chest pain
* age over 30 years

Exclusion Criteria:

* the presence of acute coronary syndromes at the moment of enrollment
* the presence of coronary stents and severe calcifications or other conditions that could interfere with image postprocessing and coronary plaque analysis
* acute renal failure of end-stage chronic kidney disease
* contraindication for iodine contrast agent administration (allergies, thyroid dysfunction, etc)
* active malignancy or history of cancer within the last 12 months prior to enrollment.
* systemic inflammatory disease, acute infections, positive SARS-CoV2 test, or other conditions that could interfere with the systemic inflammatory response.

Primary outcomes:
measure: Relationship between coronary plaque localization on its degree of vulnerability
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Relationship between systemic inflammation on coronary plaque vulnerability, according to plaque location and hemodynamic characteristics
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Targu Mures
country: Romania
facility: Cardio Med Medical Center
Study officials:
affiliation: CardioMed Medical Center
name: Diana Opincariu, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Opincariu D, Benedek T, Chitu M, Rat N, Benedek I. From CT to artificial intelligence for complex assessment of plaque-associated risk. Int J Cardiovasc Imaging. 2020 Dec;36(12):2403-2427. doi: 10.1007/s10554-020-01926-1. Epub 2020 Jul 2.
citation: Opincariu D, Rodean I, Rat N, Hodas R, Benedek I, Benedek T. Systemic Vulnerability, as Expressed by I-CAM and MMP-9 at Presentation, Predicts One Year Outcomes in Patients with Acute Myocardial Infarction-Insights from the VIP Clinical Study. J Clin Med. 2021 Jul 31;10(15):3435. doi: 10.3390/jcm10153435.
citation: Mester A, Rat N, Benedek T, Opincariu D, Hodas R, Chitu M, Benedek I. Acute-Phase Inflammatory Reaction Predicts CMR Myocardial Scar Pattern and 2-Year Mortality in STEMI Patients Undergoing Primary PCI. J Clin Med. 2022 Feb 24;11(5):1222. doi: 10.3390/jcm11051222.
citation: Opincariu D, Rat N, Mester A, et al. Site-specific Phenotype of Atherosclerotic Lesions According to Their Location Within the Coronary Tree - a CCTA-based Study of Vulnerable Plaques. Journal of Cardiovascular Emergencies 2021;7(2):39-46. DOI: 10.2478/jce-2021-0010
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