Atherosclerosis, Chronic Coronary Syndrome
Conditions
Keywords
Optical Coherence Tomography, vFFR, Shear Rate, Impedance aggregometry, Shear stress, Proteomic, Metabolomic, Computational fluid dynamics, Prothrombotic platelet, Vulnerable plaque
Brief summary
The main objective of the present study is to verify, in vivo, whether shear forces computed solely based on coronary angiography and computational fluid dynamics (CFD) techniques are associated with the biomarkers indicating the prothrombotic tendency of circulating blood in situ - distally and proximally to the coronary stenosis. The study will prospectively assess the relationship between i) the value and distribution of shear rate and shear stress (SS) estimated using three-dimensional angiography and CFD techniques, and ii) atherosclerotic plaque characteristics as assessed by optical coherence tomography (OCT), iii) functional parameters of diseased vessels assessed by vessel fractional flow reserve (vFFR), and iv) in situ platelet activation, as expressed by platelet-derived microvesicles (pMVs) and small extracellular vesicles (sEVs), platelet aggregometry and other serum prothrombotic or inflammatory biomarkers sampled within the coronary artery.
Detailed description
The biomechanical forces, including shear rate and shear stress exerted by circulating blood on the coronary wall and on circulating blood elements have been reported to contribute to the processes of plaque destabilization and thrombosis. Reliable estimation of shear (shear rate and shear stress) acting in vivo within the coronary artery has now become possible using imaging data and computational fluid dynamics techniques. The changing microenvironment of the plaque has a crucial role in the biochemical processes involved in remodeling the plaque itself. In this prospective, single-center study a total of 105 patients will be enrolled presenting with chronic coronary syndrome and angiographically confirmed coronary stenosis (30% - 90%) amenable to OCT imaging (according to the operator's judgment). The groups will be assessed at the time of angiography with: * OCT examination for precise evaluation of plaque morphology within the coronary stenosis * Computational fluid dynamics with vFFR and estimation of value and distribution of shear rate and shear stress * Impedance aggregometry-based platelet reactivity * Single-particle high-resolution flow cytometry analysis of platelet-derived microvesicles and small extracellular vesicles (sEVs) as well as additional platelet activation (P-selectin, annexin-V) and inflammatory biomarkers * Proteomic and metabolomic characterization - in the subset of patients Biomarker assessment will be done in the blood sampled directly from coronary artery (proximal and distal segment).
Interventions
DIAGNOSTIC_TESTBlood sampling
Blood sampling directly from coronary artery (proximal and distal segment) arteries
DIAGNOSTIC_TESTOCT examination
OCT examination for precise evaluation of plaque morphology within the coronary stenosis.
DIAGNOSTIC_TESTAssessment of vFFR and shear stress parameters
The procedure is based on non-invasive assessment of vFFR and shear stress parameters with dedicated software, deriving parameters directly from coronary angiography with the calculation based on the computational fluid dynamics
Sponsors
National Science Centre, Poland
University College, London
Queen Mary University of London
Medical University of Warsaw
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic coronary syndrome * Angiographically confirmed coronary stenosis (30% - 90%) * Amenable to OCT imaging
Exclusion criteria
* Cardiogenic shock * ST-segment elevation or non-ST-segment elevation myocardial infarction * Active bleeding * Left main coronary artery disease * Multivessel disease * Lesions located at a distance ≤3 mm from the ostium of the vessel * Thrombocytopenia * Previous coronary artery bypass grafting * Previous coronary intervention with stent implantation or balloon angioplasty * Previous use of novel oral anticoagulants or vitamin K antagonists
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Correlation between the mean shear rate and shear stress values at the lesion's site and the concentration of pMVs and sEVs sampled in the distal segment of the artery. | Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between the shear stress measurements at the site of the lesion and the platelet reactivity parameters in the distal segment of the artery | Baseline | Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests |
| Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of the pMVs and sEVs | Baseline | — |
| Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of inflammatory biomarkers | Baseline | Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2 |
| Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) of platelet reactivity | Baseline | Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests |
| Concentrations of inflammatory biomarkers categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel | Baseline | Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2 |
| Platelet reactivity levels categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel | Baseline | Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests |
| Correlation between the shear stress measurements at the site of the lesion and the concentration of inflammatory biomarkers in the distal segment of the artery | Baseline | Inflammatory biomarkers will include sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2 |
| Platelet reactivity levels in blood sampled from the stenosed vs. the non-stenosed coronary artery | Baseline | Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests |
| Concentrations of analyzed pMVs and sEVs in blood sampled from the stenosed vs. the non-stenosed coronary artery | Baseline | — |
| Concentrations of analyzed inflammatory biomarkers in blood sampled from the stenosed vs. the non-stenosed coronary artery | Baseline | Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2 |
| Correlation between vFFR delta pressure and the delta platelet reactivity in stenosed artery compared to these gradients in a non-stenosed artery in the same patient | Baseline | Platelet reactivity will be defined as the area under the curve of aggregation units (AU) over time using impedance aggregometry with ADP, ASPI, and TRAP-6 tests |
| Correlation between vFFR delta pressure and the delta concentration of the pMVs and sEVs in stenosed artery compared to these gradients in a non-stenosed artery in the same patient | Baseline | — |
| Correlation between vFFR delta pressure and the delta concentration of the inflammatory biomarkers in stenosed artery compared to these gradients in a non-stenosed artery in the same patient | Baseline | Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2 |
| Concentrations of pMVs and sEVs categorized by the atherosclerotic plaque morphology and the mean value of shear stress affecting the endothelium at the stenosis site and as well as according to the vessel | Baseline | — |
Countries
Poland
Contacts
Primary ContactMariusz Tomaniak
Backup ContactAdrian Bednarek
Outcome results
None listed