Mechanisms of excess risk in aortic stenosis after aortic valve replacement

ISRCTN	ISRCTN64700462
DOI	https://doi.org/10.1186/ISRCTN64700462
ClinicalTrials.gov (NCT)	NCT04627987
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	257307
Protocol serial number	125312, IRAS 257307
Sponsor	University College London
Funder	British Heart Foundation

Submission date: 15/03/2021
Registration date: 15/03/2021
Last edited: 15/03/2021

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Aortic stenosis (AS) is caused by the narrowing of one of the main heart valves, the aortic valve. When this valve narrows, it restricts blood leaving the heart and flowing to the rest of the body. Replacing the valve is the only treatment for AS. The timing of replacement is currently often too late – half of patients are left with permanent damage to the heart muscle (scarring) and a quarter die within 3.5 years. For patients with scarring, there is currently no treatment. Researchers want to change this and understand why patients who are found to have heart damage are at higher risk of dying.

Who can participate?
Patients with severe narrowing of the aortic valve, and surgical (SAVR) or transcatheter aortic valve implantation (TAVI) have been proposed as the best treatment option

What does the study involve?
The researchers will use a heart scan (MRI) to detect scarring before the valve replacement. After the valve replacement, participants will receive a tiny monitor (paper clip size) injected underneath the skin. This monitor continuously checks the heartbeat rhythm. Participants will be monitored for up to 3 years to see if scarring is linked to abnormal heart rhythms and reduced pumping function (heart failure). If participants die during the study, the monitor will help the researchers to understand what happened to their heart at that time.

What are the possible benefits and risks of participating?
If the MRI scan or the cardiac monitor identify important findings that are not known and will change treatment, the researchers will inform the cardiology or cardiac surgeon as appropriate. For example, the heart monitor may show an irregular heartbeat that requires medicine to prevent a stroke or a slow heartbeat that requires a pacemaker. The information from this study will help improve the understanding of heart disease and in the future may help decide which patients should undergo surgery.

Where is the study run from?
Barts Heart Centre, St Bartholomew’s Hospital (UK)

When is the study starting and how long is it expected to run for?
December 2020 to April 2026

Who is funding the study?
British Heart Foundation (UK)

Who is the main contact?
Dr George Thornton
george.thornton@nhs.net

Contact information

Dr Thomas Treibel
Scientific

Barts Heart Centre
St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Phone	+44 (0)7815037599
Email	thomas.treibel@nhs.net

Study information

Primary study design	Observational
Study design	Prospective single-centre observational cohort study
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	Mechanisms of excess risk in aortic stenosis after aortic valve replacement: a prospective single-centre observational cohort study
Study acronym	MASTER
Study objectives	The presence of myocardial scar (late gadolinium enhancement [LGE]/extracellular volume [ECV]) or ischaemia (reduced myocardial blood flow) measured by cardiovascular magnetic resonance (CMR) predicts the incidence of: 1. Heart failure death or hospitalisation 2. Burden of nonsustained ventricular tachycardia (NSVT) in patients following aortic valve replacement (AVR) for aortic stenosis (AS)
Ethics approval(s)	Approved 28/01/2020, London - Riverside Research Ethics Committee (Level 3 Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 (0)207104 8204; riverside.rec@hra.nhs.uk), REC ref: 19/LO/1849
Health condition(s) or problem(s) studied	Severe symptomatic aortic stenosis
Intervention	An MRI scan is carried out to detect scarring before the valve replacement. After the valve replacement, participants will receive a tiny monitor (paper clip size) injected underneath the skin. This monitor continuously checks the heartbeat rhythm. Participants will be monitored for up to 3 years to see if scarring is linked to abnormal heart rhythms and reduced pumping function (heart failure). If participants die during the study, the monitor will help the researchers to understand what happened to their heart at that time. The primary objective is to deliver a better understanding of the risk associated with AS cardiomyopathy after aortic valve replacement by identifying whether heart muscle scar (fibrosis) or its precursor, ischaemia (i.e. a mismatch of blood supply and demand), increase hospitalization for heart failure and significant heart rhythm abnormalities (arrhythmias). The primary outcome is heart failure death or hospitalisation for heart failure over a follow-up period of 3 years.
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	1. Heart failure death or hospitalisation for heart failure measured using 3 monthly telephone follow up and interrogation of Hospital Episode Statistics (HES) at the end of the study, duration of follow up is 3 years. 2. Burden of non-sustained VT, assessed using an implantable cardiac monitor via two weekly device downloads for the duration of device longevity (battery life approximately 2 years)
Key secondary outcome measure(s)	1. All-cause mortality (all-cause and cardiovascular) measured using NHS spine/death registration for 5 years after aortic valve replacement 2. Functional capacity measured using the 6-minute walk test at 6 weeks and 12 months after aortic valve replacement 3. Heart failure symptoms measured using the New York Heart Association (NYHA) functional classification (NYHA) at 6 weeks and 12 months post aortic valve surgery 4. Heart failure symptoms measured using the World Health Organisation Disability Assessment Schedule 2.0 at 6 weeks and 12 months post aortic valve surgery 5. Burden of other serious arrhythmias requiring a change in management, measured using downloads from an implantable device at 2.5 years after aortic valve replacement. 6. Participants with complete heart block, Mobitz 2 atrioventricular (AV) block, and new-onset atrial fibrillation, measured using an implantable device with device downloads at 2 weekly intervals
Completion date	01/04/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	192
Key inclusion criteria	1. Able to provide written informed consent 2. Patients with symptomatic, severe AS referred for surgical or transcatheter AVR with one out of the following echocardiographic criteria for severe AS: 2.1. Effective orifice area [EOA] <1.0 cm² 2.2. Indexed EOA of 0.6 cm²/m² 2.3. Peak velocity >4.0 m/s or mean gradient >40 mmHg
Key exclusion criteria	1. More than moderate valve disease other than AS 2. Patients that have a conventional contraindication for CMR (non-MR conditional pacemakers/implantable defibrillators, claustrophobia) 3. Renal impairment (creatinine clearance <30 ml/min/1.73m²) 4. Needle phobic patients that would preclude blood taking 5. Diagnosis of dilated or hypertrophic cardiomyopathy 6. Pregnancy/breastfeeding, eGFR <30 ml/min 7. Inability to complete the protocol, other conditions that would prevent participation in the study. 8. Adenosine stress perfusion will not be performed in those patients with: 8.1. Asthma/COPD of sufficient severity to make adenosine contraindicated 8.2. High-grade conduction disease precluding the use of adenosine 8.3. Patients with known previous allergic reactions to adenosine 8.4. LVEF <40%
Date of first enrolment	01/04/2021
Date of final enrolment	01/04/2023

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Barts Heart Centre

St Bartholomew's Hospital
King George V Building
West Smithfield
London
EC1A 7BE
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Thomas Treibel (thomas.treibel.12@ucl.ac.uk). The researchers would be prepared to provide anonymised patient-level data to researchers upon reasonable request should this be required. The degree of data sharing and other aspects would be determined on an individual request basis.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

15/03/2021: Trial's existence confirmed by London - Riverside Research Ethics Committee.