Novel Imaging Approaches To Identify Unstable Coronary Plaques

Cardiovascular disease is the leading cause of death in Scotland and the Western World. Approaches to improve the identification of vulnerable or ruptured coronary atherosclerotic plaques are urgently needed to help risk stratification, to identify patients for intensive therapies, and to provide novel biomarkers for the development of anti-atherosclerotic drug interventions. Using positron emission tomography, we have recently shown that sodium 18-fluoride uptake holds major promise as a novel marker of plaque vulnerability and rupture. Here we wish to characterise coronary atherosclerotic plaque using 128-multidetector computed tomography combined with 18-fluorodeoxyglucose and sodium 18-fluoride positron emission tomography and Virtual histology-intravascular ultrasound in 80 patients with stable and unstable coronary artery disease. This has the potential to provide an innovative and highly valuable translational model with which to test novel therapeutic interventions targeted at reducing atheroma and plaque rupture. This could have major implications for the future treatment of cardiovascular disease.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH16 4SB
      • Clinical Research Imaging Centre/ NHS LOTHIAN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The investigators will recruit two populations of 40 patients each. The first population will be patients with known stable coronary heart disease. They will have previously documented and angiographically proven coronary artery disease (≥70% luminal stenosis of a major epicardial vessel). The second population will be patients with a recent (within 30 days) acute myocardial infarction defined by the Universal definition of myocardial infarction. The culprit plaque will be defined according to the invasive coronary angiogram appearances, electrocardiogram and clinical features by two cardiologists blinded to the results of positron emission tomography.

Description

Inclusion Criteria:

Age > or = 50 yrs. Patients with Acute coronary syndromes or stable coronary artery disease.

Exclusion Criteria:

Insulin dependent diabetes Inability or unwillingness to undergo computed tomography scanning Severe renal failure (serum creatinine >250 µmol/L or estimated glomerular filtration rate <30 mL/min) Known contrast allergy Inability to give informed consent. Females in child bearing age will undergo pregnancy test if pregnancy suspected.

Participation in other research studies requiring exposure to further radiation (over and above mentioned in this study).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Acute Coronary Syndrome; 40 patients admitted with ACS (NSTEMI/STEMI) will be recruited undergo 18F NaF PET, 18F FDG and CTCA within 1 month of the event.
Stable angina cohort; 40 patients with previously diagnosed coronary artery disease and listed to undergo elective coronary angiogram will be recruited. VH-IVUS will be attempted in all patients. Selected patients will undergo PET scan after stent implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with ACS have focal 18F-NaF uptake and high tissue to background ratio(TBR) and standardised uptake values (SUV) in the culprit vessels.	Using PET/CT, the investigators will assess if there is presence of focal uptake at the areas of plaque ruptures in patients presenting with ACS. Standardised uptake values and Tissue to Background ratios of the culprit vessels with be compared with non-culprit lesions.	Within 1 month of index event
What are the morphological characteristics of plaque with high 18F-NaF tissue to background ratio or standardised uptake value	Using VH-IVUS, the investigators will look at the morphological characteristics of plaques that have higher SUVs and TBRs. Additional information about the plaque characteristics will be derived from CT coronary angiogram	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Is there a co-relation between the two PET/CT tracers(18FDG and 18F NaF) as measured as Tissue to background ratio or standardised uptake value.	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Is there a difference between the coronary and aortic TBR/SUVs in stable and unstable patients	The investigators will look for differences in activity in stable angina and ACS patients using 18F-NaF and 18F-FDG	1 month
Will patients with higher 18F-NaF uptake as measured by SUV/TBR will have higher levels of cardiac biomarkers such as hsCRP or Troponin	Blood collected from volunteers in the study will be analysed for inflammatory biomarkers such as hsCRP and Troponin	1 year

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: University of Cambridge

Publications and helpful links

General Publications

• Joshi NV, Toor I, Shah AS, Carruthers K, Vesey AT, Alam SR, Sills A, Hoo TY, Melville AJ, Langlands SP, Jenkins WS, Uren NG, Mills NL, Fletcher AM, van Beek EJ, Rudd JH, Fox KA, Dweck MR, Newby DE. Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction. J Am Heart Assoc. 2015 Aug 27;4(9):e001956. doi: 10.1161/JAHA.115.001956.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (Estimate): December 13, 2012

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: PET; inflammation; calcification; Culprit plaques; Vulnerable Plaques
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: 2011/R/CAR/13; ETM/160 (Other Grant/Funding Number: Chief Scientist Office)