Comprehensive Assessment of Morphometric, Functional, Biomechanical and Biological Interactions Between Atherosclerotic Plaque and Platelets Within the Stenosed Coronary Artery (INTERFORCE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis; Chronic Coronary Syndrome
• Intervention / Treatment: Diagnostic test: OCT examination; Diagnostic test: Blood sampling; Diagnostic test: Assessment of vFFR and shear stress parameters

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).

• Study Type: Observational
• Enrollment (Estimated): 105

Contacts and Locations

• Study Contact: Name: Mariusz Tomaniak; Phone Number: +48 22 5991951; Email: mariusz.tomaniak@wum.edu.pl
• Study Contact Backup: Name: Adrian Bednarek; Email: adikbednarek@gmail.com

Study Locations

• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 02-097
      • Recruiting
      • Medical University of Warsaw
      • Contact: Mariusz Tomaniak, MD, PhD, Assoc. Prof.; Email: mariusz.tomaniak@wum.edu.pl
      • Contact: Adrian Bednarek; Email: adikbednarek@gmail.com
      • Principal Investigator: Mariusz Tomaniak, MD, PhD, Assoc. Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with chronic coronary syndrome and coronary stenosis (30% - 90%) amenable to OCT imaging; 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.

Diagnostic test: OCT examination; OCT examination for precise evaluation of plaque morphology within the coronary stenosis.; Diagnostic test: Blood sampling; Blood sampling directly from coronary artery (proximal and distal segment) arteries; Diagnostic test: Assessment 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Inflammatory biomarkers will include sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2	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	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	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
Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) concentration of inflammatory biomarkers	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline
Correlation between the shear rate and shear stress values at the site of the lesion and the gradient (delta) of platelet reactivity	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	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	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2	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	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	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	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	Baseline
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	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2	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	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	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
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	Inflammatory biomarkers will include: sST2, sRAGE, sCD40L, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, CCL2	Baseline

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: University College, London; Queen Mary University of London; National Science Centre, Poland

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Estimated): July 21, 2025
• Study Completion (Estimated): July 21, 2026

Study Registration Dates

• First Submitted: February 7, 2024
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Vulnerable plaque; vFFR; Optical Coherence Tomography; Metabolomic; Computational fluid dynamics; Proteomic; Shear stress; Shear Rate; Impedance aggregometry; Prothrombotic platelet
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Atherosclerosis; Plaque, Atherosclerotic
• Other Study ID Numbers: INTERFORCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No