Plaque Erosion Prospective Study ii

NCT04701385 | Completed

• 1 other identifier: 270706
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Plaque erosion is associated with myocardial infarction (MI) in about 30% of cases and may require a different management approach to plaque rupture. The investigators hypothesise that plaque erosion leads to higher levels of apoptotic circulating endothelial cells (CECs) compared to plaque rupture. Aims: To compare associations between plaque erosion and plaque rupture with numbers and types of apoptotic CECs in patients with non-ST elevation MI (NSTEMI) and stable coronary artery disease controls (CAD). Additional aims are to explore signals of cellular stress (mitochondrial dsDNA), sub-populations of activated neutrophils, circulating endothelial progenitor cells and erosion-specific plasma biomarkers. Methods: Prospective observational study of 80 patients with NSTEMI and 40 patients with stable CAD. Plaque erosion or rupture will be identified by intracoronary Optical Coherence Tomography (OCT). CECs and neutrophils will be quantified and characterised using flow cytometry looking at markers of cell death and neutrophil activation. Plasma will be analysed by proteomic methods (Olink) and for mitochondrial dsDNA. Potential importance of findings: This study will provide evidence for the hypothesised mechanism of plaque erosion and clarify if biomarker analysis in NSTEMI patients provides a basis for non-invasive diagnosis of plaque erosion versus rupture.

Conditions

Atheroma; Myocardial

Keywords

Plaque Erosion; Circulating endothelial cells; Myocardial infarction; Neutrophils

Outcome Measures

Primary Outcomes (1)

• Apoptotic circulating endothelial cells

  The hypothesis is that plaque rupture myocardial infarctions are correlated with higher levels of circulating endothelial cells (100-1000 cells per ml) in blood compared to levels seen following a plaque rupture myocardial infarction (less than 100 cells per ml).To measure these levels, plasma will be taken from patient and a sample analysed using flow cytometry to determine the levels of circulating endothelial cells. Invasive assessment of their coronary arteries at the time of angioplasty with an OCT scanner will differentiate the patients cause of heart attack into plaque eruption or plaque rupture.

  1 year

Secondary Outcomes (3)

• Neutrophils

  1 year

• Endothelial progenitor cells

  1 year

• Biomarker analysis

  1 year

Study Arms (2)

NSTEMI

Patients presenting with a myocardial infarction will have blood samples taken for analysis. At the time of their angiography/angioplasty procedure they will have an OCT assessment of the culprit coronary artery to distinguish if the heart attack was caused by a plaque rupture or plaque erosion event

Diagnostic Test: Optical Coherence Tomography (OCT)

Control

Patients undergoing planned angioplasty will have blood samples taken pre and post angioplasty to help as a control for the flow cytometry and for biomarker analysis

Interventions

Optical Coherence Tomography (OCT) DIAGNOSTIC_TEST

Optical Coherence Tomography (OCT) can undertake detailed characterisation of plaque morphology in patients with myocardial infarction at the time of percutaneous treatment. This allows plaque rupture, erosion and other mechanisms of myocardial infarction to be differentiated

NSTEMI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All comers myocardial infractions/stable angina cases to the NNUH Cardiology team

You may qualify if:

• Provision of written informed consent, \< 75 years old
• NSTEMI group: Admission to hospital within 24 hr of pain onset. Scheduled to undergo invasive angiography ± PCI during index admission
• Stable angina group: Scheduled to undergo elective PCI

You may not qualify if:

• Cardiogenic shock or haemodynamic instability,
• NSTEMI due to stent thrombosis restenosis, coronary dissection or embolism
• Previous CABG
• Requirement for mechanical ventilation
• Known severe renal impairment (eGFR \<45 ml/min/1.73m2)
• Known haematological malignancy or systemic inflammatory disorder
• Requirement for emergency cardiac surgery
• Inability to carry out OCT

Sponsors & Collaborators

• Norfolk and Norwich University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum for flow cytometry and proteome analysis

MeSH Terms

Conditions

Plaque, Atherosclerotic; Myocardial Infarction

Interventions

Tomography, Optical Coherence

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Necrosis

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques

Study Officials

• James Wardley

  Specialist Trainee in Cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: January 8, 2021
• Study Start: October 15, 2020
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2023
• Last Updated: December 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)