Clinical trial NCT06275399: Comprehensive Assessment of Morphometric, Functional, Biomechanical and Biological Interactions Between Atherosclerotic Plaque and Platelets Within the Stenosed Coronary Artery
Official title: Comprehensive Assessment of Morphometric, Functional, Biomechanical, and Biological Interactions Between Atherosclerotic Plaque and Blood Platelets Within the Stenosed Coronary Artery in Vivo: a Prospective Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Coronary Syndrome
Atherosclerosis
Keywords: Optical Coherence Tomography
vFFR
Shear Rate
Impedance aggregometry
Shear stress
Proteomic
Metabolomic
Computational fluid dynamics
Prothrombotic platelet
Vulnerable plaque
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
Collaborators: name: National Science Centre, Poland
name: University College, London
name: Queen Mary University of London
First posted: 2024-02-23
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Baseline
Secondary outcomes:
measure: 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
timeFrame: Baseline
measure: Correlation between the shear stress measurements at the site of the lesion and the platelet reactivity parameters in the distal segment of the artery
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of inflammatory biomarkers
timeFrame: Baseline
measure: Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) of platelet reactivity
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: Platelet reactivity levels in blood sampled from the stenosed vs. the non-stenosed coronary artery
timeFrame: Baseline
measure: Concentrations of analyzed pMVs and sEVs in blood sampled from the stenosed vs. the non-stenosed coronary artery
timeFrame: Baseline
measure: Concentrations of analyzed inflammatory biomarkers in blood sampled from the stenosed vs. the non-stenosed coronary artery
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Medical University of Warsaw
state: Mazowieckie
Study officials:
References: