Comprehensive Assessment of Morphometric, Functional, Biomechanical and Biological Interactions Between Atherosclerotic Plaque and Platelets Within the Stenosed Coronary Artery
- Conditions
- AtherosclerosisChronic Coronary Syndrome
- Interventions
- Diagnostic Test: OCT examinationDiagnostic Test: Blood samplingDiagnostic Test: Assessment of vFFR and shear stress parameters
- Registration Number
- NCT06275399
- Lead Sponsor
- Medical University of Warsaw
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 105
- Chronic coronary syndrome
- Angiographically confirmed coronary stenosis (30% - 90%)
- Amenable to OCT imaging
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging Assessment of vFFR and shear stress parameters Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging. The groups will be assessed at the time of angiography with: * OCT for 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 pMVs and sEVs as well as additional platelet activation 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) arteries. Shear rate/shear stress distribution and biomarkers profile will be compared between the stenotic vessel and the non-stenotic vessel (stenoses \<30%) in the same patient. Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging OCT examination Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging. The groups will be assessed at the time of angiography with: * OCT for 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 pMVs and sEVs as well as additional platelet activation 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) arteries. Shear rate/shear stress distribution and biomarkers profile will be compared between the stenotic vessel and the non-stenotic vessel (stenoses \<30%) in the same patient. Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging Blood sampling Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging. The groups will be assessed at the time of angiography with: * OCT for 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 pMVs and sEVs as well as additional platelet activation 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) arteries. Shear rate/shear stress distribution and biomarkers profile will be compared between the stenotic vessel and the non-stenotic vessel (stenoses \<30%) in the same patient.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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 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 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 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
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 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 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
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 Concentrations of analyzed pMVs and sEVs in blood sampled from the stenosed vs. the non-stenosed coronary artery Baseline 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
Trial Locations
- Locations (1)
Medical University of Warsaw
🇵🇱Warsaw, Mazowieckie, Poland