ELASTIC-AS: Role of Elastin Metabolites in Aortic Remodelling in AS

Sponsor

University of Leicester (Other)

Overall Status

Unknown status

CT.gov ID

NCT03883490

Collaborator

(none)

Enrollment

Location

13.8

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Stenosis	Diagnostic Test: ECG Diagnostic Test: Blood test and biobanking Diagnostic Test: Trans-thoracic Echocardiogram Diagnostic Test: Vicorder recording Diagnostic Test: Magnetic Resonance Imaging

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Pilot Study of ELastin Metabolites and Aortic Remodelling Following Surgery for Tricuspid and bICuspid Aortic Stenosis (ELASTIC-AS)

Actual Study Start Date :

Jun 27, 2019

Anticipated Primary Completion Date :

Aug 21, 2020

Anticipated Study Completion Date :

Aug 21, 2020

Arms and Interventions

Arm	Intervention/Treatment
Bicuspid Aortic valve Patients with a bicuspid aortic valve	Diagnostic Test: ECG A 12-lead ECG will be taken for each participant. Diagnostic Test: Blood test and biobanking 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. Diagnostic Test: Trans-thoracic Echocardiogram 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. Diagnostic Test: Vicorder recording Measurement of carotid-femoral PWV will be made using the Vicorder technique. Diagnostic Test: Magnetic Resonance Imaging Patients will undergo a stress MRI scan of their heart and aorta on a 3T scanner, including 4D flow.
Tri-leaflet Aortic valve Patients with a tri-leaflet aortic valve	Diagnostic Test: ECG A 12-lead ECG will be taken for each participant. Diagnostic Test: Blood test and biobanking 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. Diagnostic Test: Trans-thoracic Echocardiogram 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. Diagnostic Test: Vicorder recording Measurement of carotid-femoral PWV will be made using the Vicorder technique. Diagnostic Test: Magnetic Resonance Imaging Patients will undergo a stress MRI scan of their heart and aorta on a 3T scanner, including 4D flow.

Arm

Intervention/Treatment

Bicuspid Aortic valve

Patients with a bicuspid aortic valve

Diagnostic Test: ECG

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

Diagnostic Test: Blood test and biobanking

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.

Diagnostic Test: Trans-thoracic Echocardiogram

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.

Diagnostic Test: Vicorder recording

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

Diagnostic Test: Magnetic Resonance Imaging

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

Tri-leaflet Aortic valve

Patients with a tri-leaflet aortic valve

Diagnostic Test: ECG

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

Diagnostic Test: Blood test and biobanking

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.

Diagnostic Test: Trans-thoracic Echocardiogram

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.

Diagnostic Test: Vicorder recording

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

Diagnostic Test: Magnetic Resonance Imaging

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

Outcome Measures

Primary Outcome Measures

Levels of metabolites of elastin turnover [12 months]
Change in levels of metabolites of elastin turnover pre- and post-AVR.

Secondary Outcome Measures

Aortic distensibility on MRI [12 months]
Aortic distensibility measured on MRI pre- and post-AVR.
Pulse wave velocity on MRI [12 months]
Pulse wave velocity (measure of aortic stiffness) measured on MRI pre- and post-AVR.
Left ventricular mass index (LVMI) on MRI [12 months]
LVMI measured on MRI (measures of cardiac remodelling) pre- and post-AVR.
Left ventricular ejection fraction (LVEF) on MRI [12 months]
LVEF measured on MRI (measures of cardiac function) pre- and post-AVR.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.