Role of Elastin Metabolites in Aortic Remodelling in AS (ELASTIC-AS)

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

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 Overview

• Status: Completed
• Conditions: Aortic Stenosis
• Intervention / Treatment: Diagnostic test: ECG; Diagnostic test: Blood test and biobanking; Diagnostic test: Trans-thoracic Echocardiogram; Diagnostic test: Vicorder recording; Diagnostic test: Magnetic Resonance Imaging

• Study Type: Observational
• Enrollment (Actual): 46

Contacts and Locations

• Study Contact: Name: Anvesha Singh, MBChB, PhD; Phone Number: +44 1162583244; Email: as707@le.ac.uk

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • University Hospitals Of Leicester Nhs Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of metabolites of elastin turnover	Change in levels of metabolites of elastin turnover pre- and post-AVR.	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2019
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Bicuspid aortic valve; Elastin Metabolites; Aorta Stiffness
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 0687

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No