Role of Elastin metabolites in aortic remodelling in AS (V1)
Research type
Research Study
Full title
A pilot study of ELastin metabolites and Aortic remodelling following Surgery for Tricuspid and bICuspid Aortic Stenosis (ELASTIC-AS)
IRAS ID
250505
Contact name
Anvesha Singh
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
1 years, 6 months, 31 days
Research summary
Research 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.
It was originally thought that the changes in the aortic wall may be a structural problem within the wall that you may be born with, but newer studies have shed light on the importance of different flow pattern of the blood in the aorta of bicuspid and tricuspid patients. We have previously studied aortic size and stiffness using MRI in patients with bicuspid and tricuspid valves with a narrowing (aortic stenosis). We now want to extend this further and 1.) measure markers in patients’ blood that may be important in the process of expansion, 2.) compare the change in MRI and blood markers at before and 6-12 months after surgery, in patients who are due to have aortic valve replacement surgery.Summary of Results
Around 1-2% of people are born with a 'bicuspid' aortic valve (BAV), with only two cusps instead of the common 'tri-leaflet' valve (TAV). People with BAV 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, we used advanced MRI imaging techniques to compare aorta of patients with BAV and the more common TAV with severe narrowing (‘aortic stenosis’ or AS) of the valve, before and 12 months after they have their valves replaced by surgery. We compared the aortic size, stiffness and flow patterns using a technique called ‘4D-flow’ on MRI. We also collected blood samples to see if markers in patients' blood may be related to differences found in the aorta. By repeating the MRI scan 12 months after valve replacement, we wanted to understand if any differences between BAV and TAV patients’ aortas were related more to the valve narrowing (in which case these would improve in both groups after valve replacement), or more related to the presence of a BAV itself. We also recruited some ‘controls’ who had a BAV or TAV, but without significant narrowing
(AS)A total of 32 patients with severe AS (11 BAV, 21 TAV) were recruited. Repeat scans after valve replacement were acquired in 25 patients (6 BAV, 19 TAV). As expected, those with BAV have larger aortas. We found that in patients with BAV and AS, there were no difference in most 4D flow parameters compared to those with TAV and AS. The only parameter that was abnormal in BAV AS was ‘flow displacement’. After valve replacement, most flow parameters improved in both BAV and TAV groups. Our data suggests that regardless of the type of valve, the narrowing of the valve (AS) leads to abnormalities in
the flow patterns in the aorta of AS patients, which may be normalised following valve repair in both BAV and TAV patients.The initial analysis done on the collected plasma has not resulted in reliable results due to problems encountered with measurement . technique. We have consent to store the collected plasma samples, which can be analysed using newer techniques in the future, if we secure more funds for this.
REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
19/EM/0035
Date of REC Opinion
29 Apr 2019
REC opinion
Further Information Favourable Opinion