Role of Elastin Metabolites in Aortic Remodelling in AS

NCT03883490 | Completed

• 1 other identifier: 0687
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Around 1-2% of people are born with a 'bicuspid' aortic valve, with only two cusps instead of the common 'tri-leaflet' valve. People with this valve develop dysfunction of the valve (narrowing or leakage) at a much earlier age. It is also more common for them to develop enlargement of the main blood vessel coming out of the heart, the aorta, and some studies suggest that they are also at higher risk of life-threatening tears in the aortic wall. Current guidelines recommend surgical replacement of the aorta at an earlier stage in these patients. The exact mechanism for the dilatation is not clear, and some studies have suggested greater 'stiffness' in the wall of the aorta. In this study, the investigators propose to 1.) study aortic size, stiffness and flow patterns using MRI in patients with bicuspid and tricuspid valves with a narrowing (aortic stenosis, 2.) measure markers in patients' blood that may be important in the process of expansion, 3.) compare the change in MRI and blood markers at before and 12 months after surgery, in patients who are due to have aortic valve replacement surgery.

Conditions

Aortic Stenosis

Keywords

Magnetic Resonance Imaging; Elastin Metabolites; Aorta Stiffness; Bicuspid aortic valve

Outcome Measures

Primary Outcomes (1)

• Levels of metabolites of elastin turnover

  Change in levels of metabolites of elastin turnover pre- and post-AVR.

  12 months

Secondary Outcomes (4)

• Aortic distensibility on MRI

  12 months

• Pulse wave velocity on MRI

  12 months

• Left ventricular mass index (LVMI) on MRI

  12 months

• Left ventricular ejection fraction (LVEF) on MRI

  12 months

Study Arms (2)

Bicuspid Aortic valve

Patients with a bicuspid aortic valve

Diagnostic Test: ECG; Diagnostic Test: Blood test and biobanking; Diagnostic Test: Trans-thoracic Echocardiogram; Diagnostic Test: Vicorder recording; Diagnostic Test: Magnetic Resonance Imaging

Tri-leaflet Aortic valve

Patients with a tri-leaflet aortic valve

Diagnostic Test: ECG; Diagnostic Test: Blood test and biobanking; Diagnostic Test: Trans-thoracic Echocardiogram; Diagnostic Test: Vicorder recording; Diagnostic Test: Magnetic Resonance Imaging

Interventions

ECG DIAGNOSTIC_TEST

A 12-lead ECG will be taken for each participant.

Bicuspid Aortic valve; Tri-leaflet Aortic valve

Blood test and biobanking DIAGNOSTIC_TEST

All patients will undergo venepuncture and blood sample will be taken for full blood count, renal function and plasma will be stored for future biomarker analysis.

Bicuspid Aortic valve; Tri-leaflet Aortic valve

Trans-thoracic Echocardiogram DIAGNOSTIC_TEST

A standard TTE will be undertaken to measure severity of AS as well as bi-ventricular function. Speckle-tracking data will be performed offline to assess diastolic function.

Bicuspid Aortic valve; Tri-leaflet Aortic valve

Vicorder recording DIAGNOSTIC_TEST

Measurement of carotid-femoral PWV will be made using the Vicorder technique.

Bicuspid Aortic valve; Tri-leaflet Aortic valve

Magnetic Resonance Imaging DIAGNOSTIC_TEST

Patients will undergo a stress MRI scan of their heart and aorta on a 3T scanner, including 4D flow.

Bicuspid Aortic valve; Tri-leaflet Aortic valve

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients listed for a surgical aortic valve replacement (with or without coronary artery bypass graft) for severe aortic stenosis of bicuspid (n=15) and tri-leaflet (n=15) aortic valves will be potentially eligible to participate in this study.

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Age 18 years or above.
• Planned surgical AVR (+/- CABG or aortic root surgery) for severe AS.
• Ability to understand the written information in English.

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• Contraindication to MRI (e.g., non-compatible pacemaker or other device).
• Severe claustrophobia (unable to have MRI scan).
• eGFR\<30ml/min (contra-indication to have contrast agent during MRI).
• Contraindication to Adenosine (severe asthma).
• Significant arrhythmia.
• Other valve disease \> moderate in severity.
• Female participants who are pregnant or lactating.
• Previous aortic valve or aorta surgery, previous CABG or other surgery involving aortic cross clamping.
• Participant in an interventional cardiovascular clinical trial.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Patient's plasma will be collected and stored for measurement of elastin metabolites and other biomarkers.

MeSH Terms

Conditions

Aortic Valve Stenosis; Bicuspid Aortic Valve Disease

Interventions

Electrocardiography; Hematologic Tests; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Clinical Laboratory Techniques; Investigative Techniques; Tomography; Diagnostic Imaging

Study Design

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

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 21, 2019
• Study Start: June 27, 2019
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: December 20, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)