Aortic Stenosis, SevereNCT05178368
MRI in Randomised Cohorts of Asymptomatic AS
An observational study of Aortic Stenosis, Severe, run by University of Leicester at 1 site in United Kingdom.
Trial summary
Aortic stenosis is narrowing of the aortic valve, and is the commonest type of valve disease requiring surgery. Current guidelines recommend waiting till patients develop symptoms (chest pain, breathlessness and dizzy spells/fainting) before possible open heart surgery to replace the valve is offered. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis, Severe
- What is being tested?
- Surgical/ Transcatheter aortic valve replacement
- Type of treatment
- Surgery or procedure
- How many people
- 202 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Jul 2021to 12 May 2026
- 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: Asymptomatic severe aortic stenosis
Who may be able to join
- Willing to and able to consent
- Participant in an RCT randomising patients with asymptomatic severe AS to early AVR vs standard care
- Severe aortic stenosis, as defined by original trial's inclusion criteria
- Asymptomatic at the time of randomisation in the RCT
- Willingness to have 1-2 cardiac MRI scan(s)
Who cannot join
- Contra-indication to MRI.
- eGFR <30.
- Severe claustrophobia (precluding MRI).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glenfield Hospital
Leicester, Leicestershire, LE3 9QP
About this study
Official title: Impact of Early Valve Replacement on Myocardial Scar in Asymptomatic Aortic Stenosis: an Observational MRI Study of Randomised Cohorts
Aortic stenosis is narrowing of the aortic valve, and is the commonest type of valve disease requiring surgery. Current guidelines recommend waiting till patients develop symptoms (chest pain, breathlessness and dizzy spells/fainting) before possible open heart surgery to replace the valve is offered. However, studies using detailed 'MRI' scanning of the heart have shown that up to half of the patients already have 'scarring' in the heart by the time symptoms develop. Furthermore, scarring is not fully reversed even after surgery and is associated with worse outcome. This suggests that some patients are being offered treatment too late. Two randomised trials in the UK (EASY AS and EVOLVED) are currently investigating if valve replacement before symptoms will result in better survival. The aim of this study is to compare the effect of early valve replacement versus waiting for symptoms, on the amount of scarring in the heart. The investigators want to know if early treatment leads to less overall scarring at the end, and leads to better quality of life and recovery after surgery. The investigators will invite participants of the EASY AS and EVOLVED trials to have 1-2 MRI heart scans: at recruitment and 2 years after being randomly allocated to early aortic valve replacement vs 'watchful waiting'. The investigators will also assess the impact of the two treatment approaches on quality of life, disability-free survival (using questionnaires) and recovery after surgery. The results from this project will increase understanding of the results of the main trials, and lead to improved selection of patients with aortic stenosis who are likely to benefit from early surgery.
Read the detailed description
Ongoing randomised control trials (RCT) are testing the strategy of early AVR in asymptomatic severe AS ('The Early surgery in severe ASYmptomatic Aortic Stenosis': EASY-AS and 'Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis': EVOLVED), and if positive, have the potential to shift the timing of intervention to earlier disease. With TAVR recently being shown to be non-inferior to SAVR in low risk, mostly symptomatic patients, this also has the potential to be extended to asymptomatic patients.
MRI studies have shown that up to 50% of those with asymptomatic AS already have scarring (LGE), which is only partially reversible even after AVE, and remains a marker of mortality. It is not known if earlier valve replacement will lead to less scar burden within the myocardium.
Patient reported outcome measures (PROM) are increasingly recognised as an important outcome measure of surgery, especially in an elderly population, for whom a significant increase in survival may be neither possible, nor sought by the patient. World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) is a standardised cross-cultural measurement of health status assessing functioning and disability in major life domains, that has been shown to be a valid and reliable instrument for assessment of disability. A comprehensive formal review of PROMS instruments in patients receiving medical treatment for heart failure concluded that the Euroqol (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were the most appropriate to measure quality of life in this group. Euroqol is the most commonly used generic instrument in Europe, and showed improvement at 1 year post-AVR for severe AS. MLHFQ is a cardiovascular disease-specific tool that has been shown to be reliable, valid and responsive to therapeutic intervention in patients undergoing valve surgery. Understanding the effect of intervention on PROMs can aid shared decision-making and help shape future individualised recommendations.
This prospective, observational mechanistic study will maximise the opportunity offered by ongoing RCTs, to try and establish the effect of the two treatment strategies (early vs late AVR) on cardiac reverse remodelling (in particular fibrosis burden), PROMs and peri-operative recovery.
- Conditions
- Aortic Stenosis, Severe
- Being tested
- Surgical/ Transcatheter aortic valve replacement
- Keywords
- myocardial fibrosis, cardiac magnetic resonance imaging, late gadolinium enhancement
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical/ Transcatheter aortic valve replacementProcedure or surgery
The choice of intervention will be made by the local clinical team. The timing of intervention will be determined by randomisation as part of the main EASY/EVOLVED trials
| Study group | Role | What they receive |
|---|---|---|
| Early aortic valve replacement | Asymptomatic severe aortic stenosis patients randomised to early aortic valve replacement Receives: Procedure: Surgical/ Transcatheter aortic valve replacement | |
| Standard care | Asymptomatic severe aortic stenosis patients randomised to 'watchful waiting' until symptom onset. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total amount of fibrosis (measured by LGE on MRI) in those randomised to early AVR vs standard care.
Measured by percentage of late gadolinium enhancement on MRI, between those randomised to early AVR vs standard care.
Measured: 2 years
Secondary outcomes (9)
Differences in patient reported outcome measures (health related quality of life) between the two groups
Measured using the questionnaire EuroQol- 5 (EQ-5D-5L)
EuroQol- 5 Dimension is a standardised measure of health-related quality of life and consists of 2 pages.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.
Measured: 2 years
Differences in patient reported outcome measures (patient perceptions of living with heart failure) between the two groups
Measured using the Minnesota Living with Heart Failure questionnaire (MLHF)
Minnesota Living with Heart Failure questionnaire aids to systematically and comprehensively assess the patient's perceptions of the effects of heart failure and its treatment on his or her daily life.
It is a 21-item paper self- administered questionnaire designed as a measure of heart failure, as indicated by its adverse effects on patients' lives. The MLHFQ quantifies a single overall score as a measure of the impact of heart failure on the patient's life.
Measured: 2 years
Differences in patient reported outcome measures (in assessing functioning and disability in major life domains) between the two groups
Measured using the World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) questionnaire
World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) is a standardised cross-cultural measurement of health status assessing functioning and disability in major life domains, that has been shown to be a valid and reliable instrument for assessment of disability. It is a 36-item measure that assesses disability in adults age 18 years and older.
Measured: 2 years
Difference in peri-operative recovery between the two groups.
Days at home within 30 days of surgery
Measured: 30 days from date of surgery
Differences in reverse remodelling (by left ventricular volume) between the two groups.
LV end-diastolic volume index in ml/m2
Measured: 2 years
Differences in reverse remodelling (by left ventricular mass) between the two groups.
LV mass index in g/m2
Measured: 2 years
Differences in reverse remodelling (by left ventricular mass/volume) between the two groups.
LV mass/volume ratio
Measured: 2 years
Differences in reverse remodelling (by left ventricular ejection fraction) between the two groups.
LV ejection fraction in %
Measured: 2 years
Differences in reverse remodelling (by myocardial perfusion reserve) between the two groups.
Myocardial perfusion reserve (in those having optional stress perfusion)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2022
- Study start28 Jul 2021
- Primary completion27 Nov 2025
- Study completion12 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic Stenosis, SevereStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- University of Edinburgh
- Responsible party
- Sponsor
- Investigators
- Anvesha Singh, Dr, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05178368
- Sponsor's protocol ID
- 0824
- Status last verified
- Jul 2026
- First submitted
- 8 Oct 2021
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Early Valve Replacement on Myocardial Scar in Asymptomatic Aortic Stenosis: an Observational MRI Study of Randomised Cohorts
- ClinicalTrials.gov ID
- NCT05178368
- Acronym / sponsor ID
- 0824
- Conditions
- Aortic Stenosis, Severe
- Keywords
- myocardial fibrosis, cardiac magnetic resonance imaging, late gadolinium enhancement
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- University of Edinburgh
- Study start
- 28 Jul 2021 (actual)
- Primary completion
- 27 Nov 2025 (actual)
- Study completion
- 12 May 2026 (actual)
- First posted
- 5 Jan 2022 (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 is narrowing of the aortic valve, and is the commonest type of valve disease requiring surgery. Current guidelines recommend waiting till patients develop symptoms (chest pain, breathlessness and dizzy spells/fainting) before possible open heart surgery to replace the valve is offered. However, studies using detailed 'MRI' scanning of the heart have shown that up to half of the patients already have 'scarring' in the heart by the time symptoms develop. Furthermore, scarring is not fully reversed even after surgery and is associated with worse outcome. This suggests that some patients are being offered treatment too late. Two randomised trials in the UK (EASY AS and EVOLVED) are currently investigating if valve replacement before symptoms will result in better survival. The aim of this study is to compare the effect of early valve replacement versus waiting for symptoms, on the amount of scarring in the heart. The investigators want to know if early treatment leads to less overall scarring at the end, and leads to better quality of life and recovery after surgery. The investigators will invite participants of the EASY AS and EVOLVED trials to have 1-2 MRI heart scans: at recruitment and 2 years after being randomly allocated to early aortic valve replacement vs 'watchful waiting'. The investigators will also assess the impact of the two treatment approaches on quality of life, disability-free survival (using questionnaires) and recovery after surgery. The results from this project will increase understanding of the results of the main trials, and lead to improved selection of patients with aortic stenosis who are likely to benefit from early surgery.
Detailed description
Ongoing randomised control trials (RCT) are testing the strategy of early AVR in asymptomatic severe AS ('The Early surgery in severe ASYmptomatic Aortic Stenosis': EASY-AS and 'Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis': EVOLVED), and if positive, have the potential to shift the timing of intervention to earlier disease. With TAVR recently being shown to be non-inferior to SAVR in low risk, mostly symptomatic patients, this also has the potential to be extended to asymptomatic patients.
MRI studies have shown that up to 50% of those with asymptomatic AS already have scarring (LGE), which is only partially reversible even after AVE, and remains a marker of mortality. It is not known if earlier valve replacement will lead to less scar burden within the myocardium.
Patient reported outcome measures (PROM) are increasingly recognised as an important outcome measure of surgery, especially in an elderly population, for whom a significant increase in survival may be neither possible, nor sought by the patient. World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) is a standardised cross-cultural measurement of health status assessing functioning and disability in major life domains, that has been shown to be a valid and reliable instrument for assessment of disability. A comprehensive formal review of PROMS instruments in patients receiving medical treatment for heart failure concluded that the Euroqol (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were the most appropriate to measure quality of life in this group. Euroqol is the most commonly used generic instrument in Europe, and showed improvement at 1 year post-AVR for severe AS. MLHFQ is a cardiovascular disease-specific tool that has been shown to be reliable, valid and responsive to therapeutic intervention in patients undergoing valve surgery. Understanding the effect of intervention on PROMs can aid shared decision-making and help shape future individualised recommendations.
This prospective, observational mechanistic study will maximise the opportunity offered by ongoing RCTs, to try and establish the effect of the two treatment strategies (early vs late AVR) on cardiac reverse remodelling (in particular fibrosis burden), PROMs and peri-operative recovery.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early aortic valve replacement | – | Procedure: Surgical/ Transcatheter aortic valve replacementAsymptomatic severe aortic stenosis patients randomised to early aortic valve replacement |
| Standard care | – | –Asymptomatic severe aortic stenosis patients randomised to 'watchful waiting' until symptom onset. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Asymptomatic severe aortic stenosis
Key inclusion criteria (5 listed)
- Willing to and able to consent
- Participant in an RCT randomising patients with asymptomatic severe AS to early AVR vs standard care
- Severe aortic stenosis, as defined by original trial's inclusion criteria
- Asymptomatic at the time of randomisation in the RCT
- Willingness to have 1-2 cardiac MRI scan(s)
Key exclusion criteria (3 listed)
- Contra-indication to MRI.
- eGFR <30.
- Severe claustrophobia (precluding MRI).
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 |
|---|---|---|
| Surgical/ Transcatheter aortic valve replacementThe choice of intervention will be made by the local clinical team. The timing of intervention will be determined by randomisation as part of the main EASY/EVOLVED trials | Procedure or surgery | Early aortic valve replacement |
Primary outcome
Total amount of fibrosis (measured by LGE on MRI) in those randomised to early AVR vs standard care.
Time frame: 2 years
Measured by percentage of late gadolinium enhancement on MRI, between those randomised to early AVR vs standard care.
9 secondary outcomes
Differences in patient reported outcome measures (health related quality of life) between the two groups
Time frame: 2 years
Differences in patient reported outcome measures (patient perceptions of living with heart failure) between the two groups
Time frame: 2 years
Differences in patient reported outcome measures (in assessing functioning and disability in major life domains) between the two groups
Time frame: 2 years
Difference in peri-operative recovery between the two groups.
Time frame: 30 days from date of surgery
Differences in reverse remodelling (by left ventricular volume) between the two groups.
Time frame: 2 years
Differences in reverse remodelling (by left ventricular mass) between the two groups.
Time frame: 2 years
Differences in reverse remodelling (by left ventricular mass/volume) between the two groups.
Time frame: 2 years
Differences in reverse remodelling (by left ventricular ejection fraction) between the two groups.
Time frame: 2 years
Differences in reverse remodelling (by myocardial perfusion reserve) between the two groups.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
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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.
Anvesha Singh, Dr principal investigator
University of Leicester
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, Severe, run by University of Leicester 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 5 inclusion and 3 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: finished, as of the sponsor's last update on 29 Jul 2026. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total amount of fibrosis (measured by LGE on MRI) in those randomised to early AVR vs standard care. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2026.