Role of Elastin Metabolites in Aortic Remodelling in AS

University of Leicester46 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Aortic Stenosis

Interventions

ECGDIAGNOSTIC_TEST

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

Blood test and biobankingDIAGNOSTIC_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.

Trans-thoracic EchocardiogramDIAGNOSTIC_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.

Vicorder recordingDIAGNOSTIC_TEST

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

Magnetic Resonance ImagingDIAGNOSTIC_TEST

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: 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.

Locations (1)

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Outcomes

Primary Outcomes

Levels of metabolites of elastin turnover

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

Time frame: 12 months

Secondary Outcomes

Aortic distensibility on MRI

Aortic distensibility measured on MRI pre- and post-AVR.

Time frame: 12 months

Pulse wave velocity on MRI

Pulse wave velocity (measure of aortic stiffness) measured on MRI pre- and post-AVR.

Time frame: 12 months

Left ventricular mass index (LVMI) on MRI

LVMI measured on MRI (measures of cardiac remodelling) pre- and post-AVR.

Time frame: 12 months

Left ventricular ejection fraction (LVEF) on MRI

LVEF measured on MRI (measures of cardiac function) pre- and post-AVR.

Time frame: 12 months

Data from ClinicalTrials.gov

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