Mitral Valve RegurgitationNCT02355418
The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation
An observational study of Mitral Valve Regurgitation and Mitral Regurgitation, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This study investigates the hypothesis that diffuse interstitial cardiac fibrosis develops in response to chronic volume overload from severe degenerative mitral regurgitation. The investigators will investigate the functional (exercise) and symptomatic (PROMS) outcomes of patients with severe but asymptomatic mitral… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mitral Valve Regurgitation, Mitral Regurgitation
- What is being tested?
- Mitral valve repair
- Type of treatment
- Surgery or procedure
- How many people
- 147 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2015to Mar 2019
- 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: Patients with asymptomatic chronic, severe primary degenerative mitral regurgitation (MR) under clinical follow-up or on the surgical waiting list at Queen Elizabeth Hospital Birmingham (QEHB). Aetiology and severity of MR will be based on the findings of echocardiography.
Who may be able to join
- All patients with asymptomatic chronic, severe primary degenerative MR known to the Queen Elizabeth Hospital Birmingham (of note, the aetiology and severity of MR will be based on the echocardiography findings , interpreted according to the European Association of Echocardiography recommendations).
Who cannot join
- symptoms due to severe MR;
- LV endsystolic diameter >45mm at baseline;
- LV ejection fraction <60%;
- history of myocardial infarction, previous coronary artery bypass graft, or valve surgery;
- inherited or acquired cardiomyopathy;
- congenital heart disease; including common atrio-ventricular canal defects;
Show all 11Show fewer
- more than mild coexisting aortic valve stenosis or regurgitation
- primary mitral regurgitation not due to degenerative disease, including rheumatic disease and infective endocarditis;
- uncontrolled atrial fibrillation (resting HR>100/min average on 24 hour Holter );
- unable to undergo CMR;
- unable to walk on treadmill or use supine bicycle.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital Birmingham
Birmingham, West Midlands, B15 2TH
About this study
Official title: A Prospective Observational Study Examining the Role of Myocardial Fibrosis in Outcome Following Mitral Valve Repair in Degenerative Mitral Regurgitation.
This study investigates the hypothesis that diffuse interstitial cardiac fibrosis develops in response to chronic volume overload from severe degenerative mitral regurgitation. The investigators will investigate the functional (exercise) and symptomatic (PROMS) outcomes of patients with severe but asymptomatic mitral regurgitation who have the option of choosing surgical repair or watchful waiting.
Read the detailed description
The optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve, but timing of surgery remains controversial. Current guidelines suggest 'watchful waiting' until the onset of symptoms or left ventricular dysfunction but have been criticized for promoting 'rescue surgery'. Better predictors are required to optimize timing of surgery and patient outcomes.
Chronic volume overload is a stimulus for adverse adaptive left ventricular (LV) remodeling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect myocardial fibrosis. The investigators' pilot cardiac magnetic resonance (CMR) data support this hypothesis. The aims of this study are:
- identify whether diffuse interstitial myocardial fibrosis impacts upon post-operative complications, symptomatic improvement and ventricular recovery following surgery,
- to show that diffuse fibrosis (assessed by T1 mapping CMR) is validated by histological assessment on myocardial biopsy,
- identify independent pre-operative imaging / biomarker / exercise predictors of post-operative clinical outcomes
The investigators will investigate and follow up patients with severe degenerative mitral regurgitation, who do meet a class 1 indication for mitral valve surgery using present AHA guidelines. Patients have the option of choosing either close monitoring or early surgical repair of their mitral valve (class 2a indication). The relationship between patient symptoms, CMR findings, blood and histological measures of fibrosis will be studied and correlated with patient outcomes.
- Conditions
- Mitral Valve Regurgitation, Mitral Regurgitation
- Being tested
- Mitral valve repair
- Medical subject headings
- Mitral Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitral valve repairProcedure or surgery
Standard mitral valve repair surgery
| Study group | Role | What they receive |
|---|---|---|
| Patients for early surgery | A prospective, cross sectional comparison of asymptomatic patients before and after mitral valve repair surgery for chronic severe primary degenerative mitral regurgitation.Once established, it is our intention to restudy subjects in 5 years to provide information on late outcome following surgery. Receives: Procedure: Mitral valve repair | |
| Patients against early surgery | In order to establish the natural history of diffuse fibrosis in mitral regurgitation, an additional cohort of patients with asymptomatic mitral regurgitation who do not wish to consider early repair will be followed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation and evaluation of its functional consequences.
Using T1-mapping CMR and myocardial biopsy, the investigators can confirm the development of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation. Using a range of clinical markers, the investigators will study the development of diffuse interstitial fibrosis and its relationship to left ventricular recovery following surgery, length of in-hospital stay, and patients' functional (exercise) and symptomatic (PROMS) status.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2015 (estimated)
- Study startSep 2015
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mitral Valve RegurgitationStudies 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
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Principal investigator, Boyang Liu, University Hospital Birmingham NHS Foundation Trust
- Investigators
- Richard Steeds, Principal investigator, University Hospital Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02355418
- Sponsor's protocol ID
- Not yet available
- Status last verified
- Mar 2022
- First submitted
- 30 Jan 2015
- Last updated
- 14 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Liu B, Neil DAH, Bhabra M, Patel R, Barker TA, Nikolaidis N, Billing JS, Hayer M, Baig S, Price AM, Vijapurapu R, Treibel TA, Edwards NC, Steeds RP. Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation. JACC Cardiovasc Imaging. 2022 Feb;15(2):224-236. doi: 10.1016/j.jcmg.2021.07.007. Epub 2021 Aug 18.
PubMed 34419393Liu B, Neil DAH, Premchand M, Bhabra M, Patel R, Barker T, Nikolaidis N, Billing JS, Treibel TA, Moon JC, Gonzalez A, Hodson J, Edwards NC, Steeds RP. Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2020 Dec 14;22(1):86. doi: 10.1186/s12968-020-00674-4.
PubMed 33308240Liu B, Edwards NC, Neal DAH, Weston C, Nash G, Nikolaidis N, Barker T, Patel R, Bhabra M, Steeds RP. A prospective study examining the role of myocardial Fibrosis in outcome following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and design of the mitral FINDER study. BMC Cardiovasc Disord. 2017 Nov 22;17(1):282. doi: 10.1186/s12872-017-0715-y.
PubMed 29166877
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Study Examining the Role of Myocardial Fibrosis in Outcome Following Mitral Valve Repair in Degenerative Mitral Regurgitation.
- ClinicalTrials.gov ID
- NCT02355418
- Acronym / sponsor ID
- Not yet available
- Conditions
- Mitral Valve Regurgitation, Mitral Regurgitation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- Sep 2015 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 4 Feb 2015 (estimated)
- 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.
This study investigates the hypothesis that diffuse interstitial cardiac fibrosis develops in response to chronic volume overload from severe degenerative mitral regurgitation. The investigators will investigate the functional (exercise) and symptomatic (PROMS) outcomes of patients with severe but asymptomatic mitral regurgitation who have the option of choosing surgical repair or watchful waiting.
Detailed description
The optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve, but timing of surgery remains controversial. Current guidelines suggest 'watchful waiting' until the onset of symptoms or left ventricular dysfunction but have been criticized for promoting 'rescue surgery'. Better predictors are required to optimize timing of surgery and patient outcomes.
Chronic volume overload is a stimulus for adverse adaptive left ventricular (LV) remodeling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect myocardial fibrosis. The investigators' pilot cardiac magnetic resonance (CMR) data support this hypothesis. The aims of this study are:
- identify whether diffuse interstitial myocardial fibrosis impacts upon post-operative complications, symptomatic improvement and ventricular recovery following surgery,
- to show that diffuse fibrosis (assessed by T1 mapping CMR) is validated by histological assessment on myocardial biopsy,
- identify independent pre-operative imaging / biomarker / exercise predictors of post-operative clinical outcomes
The investigators will investigate and follow up patients with severe degenerative mitral regurgitation, who do meet a class 1 indication for mitral valve surgery using present AHA guidelines. Patients have the option of choosing either close monitoring or early surgical repair of their mitral valve (class 2a indication). The relationship between patient symptoms, CMR findings, blood and histological measures of fibrosis will be studied and correlated with patient outcomes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients for early surgery | – | Procedure: Mitral valve repairA prospective, cross sectional comparison of asymptomatic patients before and after mitral valve repair surgery for chronic severe primary degenerative mitral regurgitation.Once established, it is our intention to restudy subjects in 5 years to provide information on late outcome following surgery. |
| Patients against early surgery | – | –In order to establish the natural history of diffuse fibrosis in mitral regurgitation, an additional cohort of patients with asymptomatic mitral regurgitation who do not wish to consider early repair will be followed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with asymptomatic chronic, severe primary degenerative mitral regurgitation (MR) under clinical follow-up or on the surgical waiting list at Queen Elizabeth Hospital Birmingham (QEHB). Aetiology and severity of MR will be based on the findings of echocardiography.
Key inclusion criteria (1 listed)
- All patients with asymptomatic chronic, severe primary degenerative MR known to the Queen Elizabeth Hospital Birmingham (of note, the aetiology and severity of MR will be based on the echocardiography findings , interpreted according to the European Association of Echocardiography recommendations).
Key exclusion criteria (11 listed)
- symptoms due to severe MR;
- LV endsystolic diameter >45mm at baseline;
- LV ejection fraction <60%;
- history of myocardial infarction, previous coronary artery bypass graft, or valve surgery;
- inherited or acquired cardiomyopathy;
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 |
|---|---|---|
| Mitral valve repairStandard mitral valve repair surgery | Procedure or surgery | Patients for early surgery |
Primary outcome
Detection of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation and evaluation of its functional consequences.
Time frame: 3 years
Using T1-mapping CMR and myocardial biopsy, the investigators can confirm the development of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation. Using a range of clinical markers, the investigators will study the development of diffuse interstitial fibrosis and its relationship to left ventricular recovery following surgery, length of in-hospital stay, and patients' functional (exercise) and symptomatic (PROMS) status.
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 14 Mar 2022.
- Derived from this study: PubMed 34419393Liu B, Neil DAH, Bhabra M, Patel R, Barker TA, Nikolaidis N, Billing JS, Hayer M, Baig S, Price AM, Vijapurapu R, Treibel TA, Edwards NC, Steeds RP. Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation. JACC Cardiovasc Imaging. 2022 Feb;15(2):224-236. doi: 10.1016/j.jcmg.2021.07.007. Epub 2021 Aug 18.
- Derived from this study: PubMed 33308240Liu B, Neil DAH, Premchand M, Bhabra M, Patel R, Barker T, Nikolaidis N, Billing JS, Treibel TA, Moon JC, Gonzalez A, Hodson J, Edwards NC, Steeds RP. Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2020 Dec 14;22(1):86. doi: 10.1186/s12968-020-00674-4.
- Derived from this study: PubMed 29166877Liu B, Edwards NC, Neal DAH, Weston C, Nash G, Nikolaidis N, Barker T, Patel R, Bhabra M, Steeds RP. A prospective study examining the role of myocardial Fibrosis in outcome following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and design of the mitral FINDER study. BMC Cardiovasc Disord. 2017 Nov 22;17(1):282. doi: 10.1186/s12872-017-0715-y.
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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.
Richard Steeds principal investigator
University Hospital Birmingham
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 Mitral Valve Regurgitation and Mitral Regurgitation, run by University Hospital Birmingham NHS Foundation Trust 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 11 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 14 Mar 2022. 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?
Detection of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation and evaluation of its functional consequences. (time frame: 3 years). 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 NCT02355418, which also lists 3 linked publications.
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 14 Mar 2022.