Aortic StenosisMASTERNCT04627987
Mechanisms of Excess Risk in Aortic Stenosis
An observational study of Aortic Stenosis and Non-Sustained VT, run by University College, London at 1 site in United Kingdom.
Trial summary
Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis, Non-Sustained VT, Heart Failure
- What is being tested?
- Cardiac MRI scan, Serum biomarkers (High sensitivity troponin, NT-proBNP and Implantable Loop Recorder
- Type of treatment
- Surgery or procedure
- How many people
- 192 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Mar 2021to 1 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This is a prospective single centre, observational cohort study of patients with symptomatic severe AS (n=192) undergoing clinically indicated AVR (surgical or transcatheter) and multiparametric assessment by CMR prior to AVR.
Who may be able to join
- Patients with symptomatic severe aortic stenosis referred for surgical or transcatheter AVR (one out of: effective orifice area [EOA] <1.0 cm2 , indexed EOA of 0.6cm/m2, peak velocity >4.0 m/s or mean gradient >40mmHg).
Who cannot join
- More than moderate valve disease other than AS
- Diagnosis of dilated or hypertrophic cardiomyopathy, pregnancy/breast feeding
- eGFR <30ml/min, CMR incompatible devices
- Inability to complete the protocol
- Other conditions that would prevent participation in the study.
- Adenosine perfusion will not be performed in patients with AV block, severe asthma/COPD or LVEF<40%.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Barts Heart Centre
London, EC1A 7BE
Thomas Treibel, MBBS PhD, 020 3416 5000, thomas.treibel.12@ucl.ac.uk
Thomas A Treibel, MBBS PhD
About this study
Official title: Mechanisms of Excess Risk in Aortic STEnosis After Aortic Valve Replacement
Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years.
Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this.
Read more
In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure.
Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.
Read the detailed description
Valvular heart disease (VHD) affects around 1.5 million people above the age of 65 across the UK and is set to nearly double by 2050. Aortic Stenosis (AS) is the most common VHD in the UK, affecting 3% of those over 75 with more than 11,000 people requiring aortic valve replacement (AVR) in the UK each year (>100,000 world-wide). Current guidelines recommend AVR to improve survival and symptom status when AS symptoms emerge or there is a reduction in left ventricle (LV) function (1), but years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators, and others, have shown that these changes lead to an excess in morbidity and mortality, but the mechanisms of increased risk is unclear.
Patients undergoing aortic valve replacement for severe aortic stenosis have a shorter life expectancy compared with the general population (2). Years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators and others have shown that these changes to the heart muscle are associated with poor outcome. But the mechanism of how heart muscle damage leads to excess mortality is poorly understood.
The proposed study will enhance our understanding of the residual risk after AVR and reveal the modes and substrate of mortality. Heart failure and heart rhythm disturbances (arrhythmias) are likely downstream effects of heart muscle damage, but without understanding the mode of death (heart failure, arrhythmia or other), the investigators are unable to target therapeutic strategies to improve outcomes.
- Conditions
- Aortic Stenosis, Non-Sustained VT, Heart Failure
- Being tested
- Cardiac MRI scan, Serum biomarkers (High sensitivity troponin, NT-proBNP, Implantable Loop Recorder, 6 minute walk test, Echocardiogram
- Keywords
- Late gadolinium enhancement, Tissue characterisation, Arrhythmia, Sudden cardiac death, Heart failure, Aortic stenosis, Myocardial remodelling
- Medical subject headings
- Aortic Valve Stenosis, Heart Failure, Arrhythmias, Cardiac, Death, Sudden, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRI scanDiagnostic test
Cardiac MRI scan pre- and post- aortic valve replacement to assess degree of left ventricular remodelling, fibrosis and myocardial blood flow.
Serum biomarkers (High sensitivity troponin, NT-proBNPDiagnostic test
Blood tests looking evidence of cardiac structural remodelling and function.
Implantable Loop RecorderProcedure or surgery
Determine post-AVR arrhythmia burden
6 minute walk testDiagnostic test
Validated assessment of functional capacity - distance walked over 6 minute time frame.
EchocardiogramDiagnostic test
Ultrasound assessment of heart structure and function. Standard of care in valve surgery pathway.
| Study group | Role | What they receive |
|---|---|---|
| Main study | Patients with severe, symptomatic aortic stenosis will be recruited and followed up with primary outcome of heart failure death and hospitalisation (n=192). Of these, 170 will have an implantable cardiac monitor placed to detect presence and burden of non-sustained VT. Receives: Diagnostic Test: Cardiac MRI scan; Diagnostic Test: Serum biomarkers (High sensitivity troponin, NT-proBNP; Procedure: Implantable Loop Recorder; Diagnostic Test: 6 minute walk test; Diagnostic Test: Echocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart failure death or hospitalisation for heart failure.
Measured: 5 years after aortic valve replacement
Burden of non-sustained VT
As assessed on implantable cardiac monitor (approximate battery life 2.5 years)
Measured: 2.5 years after aortic valve replacement.
Secondary outcomes (5)
All-cause mortality (all-cause and cardiovascular via NHS spine/death registration)
Measured: 5 years after aortic valve replacement
change in functional capacity (6-minute walk test)
Measured: At 6 weeks and 12 months after aortic valve replacement.
Heart failure symptoms
New York Heart Association (NYHA) functional classification (NYHA 1 least symptomatic, 4 most symptomatic)
Measured: At 6 weeks and 12 months post aortic valve surgery
Heart failure symptoms
World Health Organisation Disability Assessment Schedule 2.0 (Higher score indicates greater disability)
Measured: At 6 weeks and 12 months post aortic valve surgery
Burden of other serious arrhythmias requiring change in management
Participants with complete heart block, Mobitz 2 AV block, new onset atrial fibrillation
Measured: 2.5 years after aortic valve replacement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2020
- Study start23 Mar 2021
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 192 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Barts & The London NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04627987
- Sponsor's protocol ID
- 125312
- Acronym
- MASTER
- Status last verified
- Apr 2021
- First submitted
- 6 Nov 2020
- Last updated
- 30 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bennett J, Thornton GD, Nitsche C, Gama FF, Aziminia N, Gul U, Shetye A, Kellman P, Davies RH, Moon JC, Treibel TA; Barts Valve and Imaging Group. Left Ventricular Hypertrophy in Aortic Stenosis: Early Cell and Matrix Regression 2 Months Post-Aortic Valve Replacement. Circ Cardiovasc Imaging. 2024 Dec;17(12):e017425. doi: 10.1161/CIRCIMAGING.124.017425. Epub 2024 Dec 4.
PubMed 39629586
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Excess Risk in Aortic STEnosis After Aortic Valve Replacement
- ClinicalTrials.gov ID
- NCT04627987
- Acronym / sponsor ID
- MASTER / 125312
- Conditions
- Aortic Stenosis, Non-Sustained VT, Heart Failure
- Keywords
- Late gadolinium enhancement, Tissue characterisation, Arrhythmia, Sudden cardiac death, Heart failure, Aortic stenosis, Myocardial remodelling
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 192 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Barts & The London NHS Trust
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 13 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years.
Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this.
In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure.
Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.
Detailed description
Valvular heart disease (VHD) affects around 1.5 million people above the age of 65 across the UK and is set to nearly double by 2050. Aortic Stenosis (AS) is the most common VHD in the UK, affecting 3% of those over 75 with more than 11,000 people requiring aortic valve replacement (AVR) in the UK each year (>100,000 world-wide). Current guidelines recommend AVR to improve survival and symptom status when AS symptoms emerge or there is a reduction in left ventricle (LV) function (1), but years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators, and others, have shown that these changes lead to an excess in morbidity and mortality, but the mechanisms of increased risk is unclear.
Patients undergoing aortic valve replacement for severe aortic stenosis have a shorter life expectancy compared with the general population (2). Years of excessive haemodynamic load result in an "AS cardiomyopathy" with LV hypertrophy, remodelling, diffuse and focal scar. The investigators and others have shown that these changes to the heart muscle are associated with poor outcome. But the mechanism of how heart muscle damage leads to excess mortality is poorly understood.
The proposed study will enhance our understanding of the residual risk after AVR and reveal the modes and substrate of mortality. Heart failure and heart rhythm disturbances (arrhythmias) are likely downstream effects of heart muscle damage, but without understanding the mode of death (heart failure, arrhythmia or other), the investigators are unable to target therapeutic strategies to improve outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Main study | – | Diagnostic Test: Cardiac MRI scan, Diagnostic Test: Serum biomarkers (High sensitivity troponin, NT-proBNP, Procedure: Implantable Loop Recorder, Diagnostic Test: 6 minute walk test, Diagnostic Test: EchocardiogramPatients with severe, symptomatic aortic stenosis will be recruited and followed up with primary outcome of heart failure death and hospitalisation (n=192). Of these, 170 will have an implantable cardiac monitor placed to detect presence and burden of non-sustained VT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This is a prospective single centre, observational cohort study of patients with symptomatic severe AS (n=192) undergoing clinically indicated AVR (surgical or transcatheter) and multiparametric assessment by CMR prior to AVR.
Key inclusion criteria (1 listed)
- Patients with symptomatic severe aortic stenosis referred for surgical or transcatheter AVR (one out of: effective orifice area [EOA] <1.0 cm2 , indexed EOA of 0.6cm/m2, peak velocity >4.0 m/s or mean gradient >40mmHg).
Key exclusion criteria (6 listed)
- More than moderate valve disease other than AS
- Diagnosis of dilated or hypertrophic cardiomyopathy, pregnancy/breast feeding
- eGFR <30ml/min, CMR incompatible devices
- Inability to complete the protocol
- Other conditions that would prevent participation in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac MRI scanCardiac MRI scan pre- and post- aortic valve replacement to assess degree of left ventricular remodelling, fibrosis and myocardial blood flow. | Diagnostic test | Main study |
| Serum biomarkers (High sensitivity troponin, NT-proBNPBlood tests looking evidence of cardiac structural remodelling and function. | Diagnostic test | Main study |
| Implantable Loop RecorderDetermine post-AVR arrhythmia burden | Procedure or surgery | Main study |
| 6 minute walk testValidated assessment of functional capacity - distance walked over 6 minute time frame. | Diagnostic test | Main study |
| EchocardiogramUltrasound assessment of heart structure and function. Standard of care in valve surgery pathway. | Diagnostic test | Main study |
Primary outcome
Heart failure death or hospitalisation for heart failure.
Time frame: 5 years after aortic valve replacement
Burden of non-sustained VT
Time frame: 2.5 years after aortic valve replacement.
As assessed on implantable cardiac monitor (approximate battery life 2.5 years)
5 secondary outcomes
All-cause mortality (all-cause and cardiovascular via NHS spine/death registration)
Time frame: 5 years after aortic valve replacement
change in functional capacity (6-minute walk test)
Time frame: At 6 weeks and 12 months after aortic valve replacement.
Heart failure symptoms
Time frame: At 6 weeks and 12 months post aortic valve surgery
Heart failure symptoms
Time frame: At 6 weeks and 12 months post aortic valve surgery
Burden of other serious arrhythmias requiring change in management
Time frame: 2.5 years after aortic valve replacement
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2021.
- Derived from this study: PubMed 39629586Bennett J, Thornton GD, Nitsche C, Gama FF, Aziminia N, Gul U, Shetye A, Kellman P, Davies RH, Moon JC, Treibel TA; Barts Valve and Imaging Group. Left Ventricular Hypertrophy in Aortic Stenosis: Early Cell and Matrix Regression 2 Months Post-Aortic Valve Replacement. Circ Cardiovasc Imaging. 2024 Dec;17(12):e017425. doi: 10.1161/CIRCIMAGING.124.017425. Epub 2024 Dec 4.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Stenosis and Non-Sustained VT, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Thomas A Treibel, MBBS PhD (020 3416 5000, thomas.treibel.12@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart failure death or hospitalisation for heart failure. (time frame: 5 years after aortic valve replacement). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04627987, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2021.