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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic coronary syndrome
- •Angiographically confirmed coronary stenosis (30% - 90%)
- •Amenable to OCT imaging
排除标准
- •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
结局指标
主要结局
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.
时间窗: Baseline
次要结局
- 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)
- 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)
- 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)
- Concentrations of analyzed inflammatory biomarkers in blood sampled from the stenosed vs. the non-stenosed coronary artery(Baseline)
- 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)
- Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of inflammatory biomarkers(Baseline)
- 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)
- Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) of platelet reactivity(Baseline)
- 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)
- 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)
- 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)
研究者
Mariusz Tomaniak
Tomaniak Mariusz MD PhD Assoc. Prof.
Medical University of Warsaw