Mitral RegurgitationRIPCOM1NCT03155373
The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study
An observational study of Mitral Regurgitation and Pulmonary Hypertension, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Mitral regurgitation (MR) is a prevalent valvular heart pathology. Indications for surgery include symptoms, impaired left ventricular function or enlarging dimensions, new onset atrial fibrillation, pulmonary hypertension, asymptomatic status with a high likelihood of success. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Mitral Regurgitation, Pulmonary Hypertension
- What is being tested?
- Cardiac catheterisation, Cardiopulmonary exercise testing and Pulmonary function tests
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Feb 2017to 1 Mar 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing cardiac surgery for severe primary/degenerative mitral regurgitation under the current guidelines.
Who may be able to join
- Patients listed for surgery for severe primary mitral regurgitation +/- concomitant coronary artery bypass grafting for bystander disease +/- tricuspid valve surgery +/- atrial fibrillation surgery.
Who cannot join
- Secondary mitral regurgitation. Significant history of ischaemic heart disease eg. angina. Age <18 years or >85 years. Critical preoperative status with multi-organ dysfunction. Emergency cardiac surgical intervention. Pregnancy. Unable to give informed consent or unwilling to participate in research. Patients with definite contraindication for MRI would be excluded from the cardiac MRI element of the study.
- Patients we are unable to take adequate biopsies due to technical difficulties would be excluded from the myocardial biopsy element of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease
Mitral regurgitation (MR) is a prevalent valvular heart pathology. Indications for surgery include symptoms, impaired left ventricular function or enlarging dimensions, new onset atrial fibrillation, pulmonary hypertension, asymptomatic status with a high likelihood of success.
Asymptomatic severe primary MR can be initially monitored without impairing long term survival. However, significant symptoms or impairment of left ventricular function is associated with worse prognosis due to long term heart failure. Some physicians wait for early symptoms before referring for surgery and this is reflected by a great variation in referral patterns, but symptomatic status is subjective and difficult to assess. Nearly all of the surgical indications are based on expert opinion rather than significant evidence base.
The primary aim of this project is to improve the current guidelines for surgery for primary MR by finding an objective marker of functional capacity which correlates with surrogates of prognosis and detects early decline, but returns to normal after surgery.
Read the detailed description
The current indications for surgery for MR include symptomatic status; asymptomatic status with echocardiographic features such as impaired left ventricular function or increased left ventricular dimensions; new onset atrial fibrillation or pulmonary hypertension; asymptomatic status with a high likelihood of durable repair and low co-morbidity. The limitation in strength of the current evidence base is reflected by the class of evidence being expert opinion (level C) for all of the above indications with the sole exception of symptomatic patients, which is level B.
The fulcrum point between asymptomatic status and symptomatic status at which patients would derive prognostic benefit and thus should be referred for surgery on prognostic grounds still remains unclear and controversial. Although elective mitral valve repair carries a low risk of mortality, it has been demonstrated that asymptomatic patients with severe degenerative MR can be safely followed up before becoming symptomatic or reaching cutoff values for left ventricular dimensions, size or pulmonary hypertension; with no significant difference with expected survival. As a result, it is debatable whether prophylactic surgery for all patients with asymptomatic severe degenerative MR derives prognostic benefit.
At the other end of the clinical spectrum, the increased operative mortality and worse long term prognosis of symptomatic patients is well proven. Patients with New York Heart Association Class III or IV status have excessive operative mortality and significantly increased mortality at 10 years. Both this study and another have demonstrated that preoperative ejection fraction is an independent predictor of long term survival. Although this evidence base does not support prophylactic surgery on asymptomatic patients, it does highlight the importance of avoiding the long term sequelae of MR in causing symptomatic status or left ventricular impairment. Hence attention has turned to objective markers or investigations independent of symptomatic status that may be subjectively assessed in the early phases; to help identify patients who would prognostically benefit from earlier surgical intervention.
In summary, severe mitral regurgitation is a common valvular pathology that causes a significant burden of disease. Current guidelines for timing of operative intervention are mostly based on expert opinion rather than randomised trials or studies. The ideal tipping point investigation will be an objective marker of functional capacity which correlates with known surrogates of survival such as left ventricular function; and detects early decline, but returns to normal after successful surgery. The improved evidence base will create an epidemiological shift in patterns of referring for mitral valve surgery and reduce the burden of disease of heart failure.
Patients will undergo the following investigations:
Right heart catheterisation- It is the usual gold standard practice at our institution for patients to have a right heart catheterisation before being referred for surgery. Those who have not had one may be referred to the Department of Cardiology at Hammersmith Hospital for this test.
Cardiac MRI- patients will have a T1 weighted cardiac MRI. One strength of cardiac MRI over transthoracic echocardiogram is objective measurements of right heart function. Parameters measured will be ventricular ejection fraction and dimensions, patterns of myocardial fibrosis.
Cardiopulmonary exercise testing (CPEX)- CPEX is a quantitative and validated method of assessing cardiorespiratory function and exercise capacity with commonly measured variables including maximal oxygen consumption (VO2 max) and the clearance of carbon dioxide during exercise (Ve/VCO2). The patient's gaseous exchange is monitored during a 3 minute rest period, a three minute "rolling basal" period when they perform exercise on a bicycle with no load; and subsequently during the exercise phase when the work load increases at a rate of 30 Watts per minute. Exercise continues until the patient has to stop or achieves predicted maximum heart rate.
Pulmonary function tests- Patients will have routine spirometry tests and also assessment of transfer factor.
Transthoracic echocardiogram- It is normal practice for patients to have an echocardiogram at preassessment clinic to assess biventricular function, dimensions and cardiac structural disease.
Quality of life questionnaire- Patients will be asked to fill out a validated questionnaire (SF-36 health survey).
- Conditions
- Mitral Regurgitation, Pulmonary Hypertension
- Being tested
- Cardiac catheterisation, Cardiopulmonary exercise testing, Pulmonary function tests, Cardiac MRI, Quality of life survey
- Keywords
- Cardiopulmonary exercise testing
- Medical subject headings
- Mitral Valve Insufficiency, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac catheterisationDiagnostic test
Pre-operative left heart catheterisation +/- right heart catheterisation
Cardiopulmonary exercise testingDiagnostic test
Pre and post-operative cardiopulmonary exercise testing
Pulmonary function testsDiagnostic test
Pre and post-operative pulmonary function tests
Cardiac MRIDiagnostic test
Pre and post-operative cardiac MRI
Quality of life surveyOther
Pre and post-operative quality of life survey (SF36)
Mitral valve operationProcedure or surgery
Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery
Myocardial biopsiesProcedure or surgery
Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery
| Study group | Role | What they receive |
|---|---|---|
| A | Asymptomatic/mild symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction >60%) Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies | |
| B | Symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction greater than or equal to 60%) Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies | |
| C | Patients with impaired pre-operative left ventricular function (defined as left ventricular ejection fraction <60%) Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impaired Post-operative Functional Capacity
Dichotomic variable of post-operative left ventricular ejection < 50% and/or post-operative percentage predicted peak VO2 <= 84%
Measured: 1 year
Imaging Data
Correlation between transthoracic echocardiogram and cardiac MRI parameters
Measured: 1 year
Secondary outcomes (3)
Right Heart Catheterisation
Accuracy of measurements of pre-op pulmonary artery pressures against the gold standard of right heart catheterisation
Measured: Pre-op
Quality of Life as Assessed by SF36 Survey
Changes in quality of life measured on the SF36 survey after surgery
Measured: Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)
Myocardial Histology
Quantification of myocardial fibrosis on right and left ventricular biopsies
Measured: At surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start15 Feb 2017
- Primary completion1 Mar 2019
- Study completion1 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mitral RegurgitationStudies of the same condition, open and under way.
- More trials run by Imperial 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
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prakash Punjabi, FRCS, Principal investigator, Imperial College LondonSimon Gibbs, FRCP, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03155373
- Sponsor's protocol ID
- 16HH3639
- Other IDs
- 16/LO/2127, 199676
- Acronym
- RIPCOM1
- Status last verified
- Feb 2023
- First submitted
- 15 May 2017
- Last updated
- 28 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Afoke J, Gibbs S, Kanaganayagam S, Bruno D, Howard L, Punjabi P. Changes in cardiopulmonary exercise testing variables after surgery for primary mitral regurgitation. Perfusion. 2026 Mar;41(2):165-172. doi: 10.1177/02676591251346035. Epub 2025 May 27.
PubMed 40424530
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease
- ClinicalTrials.gov ID
- NCT03155373
- Acronym / sponsor ID
- RIPCOM1 / 16HH3639
- Conditions
- Mitral Regurgitation, Pulmonary Hypertension
- Keywords
- Cardiopulmonary exercise testing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 15 Feb 2017 (actual)
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 16 May 2017 (actual)
- Results
- Posted 28 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mitral regurgitation (MR) is a prevalent valvular heart pathology. Indications for surgery include symptoms, impaired left ventricular function or enlarging dimensions, new onset atrial fibrillation, pulmonary hypertension, asymptomatic status with a high likelihood of success.
Asymptomatic severe primary MR can be initially monitored without impairing long term survival. However, significant symptoms or impairment of left ventricular function is associated with worse prognosis due to long term heart failure. Some physicians wait for early symptoms before referring for surgery and this is reflected by a great variation in referral patterns, but symptomatic status is subjective and difficult to assess. Nearly all of the surgical indications are based on expert opinion rather than significant evidence base.
The primary aim of this project is to improve the current guidelines for surgery for primary MR by finding an objective marker of functional capacity which correlates with surrogates of prognosis and detects early decline, but returns to normal after surgery.
Detailed description
The current indications for surgery for MR include symptomatic status; asymptomatic status with echocardiographic features such as impaired left ventricular function or increased left ventricular dimensions; new onset atrial fibrillation or pulmonary hypertension; asymptomatic status with a high likelihood of durable repair and low co-morbidity. The limitation in strength of the current evidence base is reflected by the class of evidence being expert opinion (level C) for all of the above indications with the sole exception of symptomatic patients, which is level B.
The fulcrum point between asymptomatic status and symptomatic status at which patients would derive prognostic benefit and thus should be referred for surgery on prognostic grounds still remains unclear and controversial. Although elective mitral valve repair carries a low risk of mortality, it has been demonstrated that asymptomatic patients with severe degenerative MR can be safely followed up before becoming symptomatic or reaching cutoff values for left ventricular dimensions, size or pulmonary hypertension; with no significant difference with expected survival. As a result, it is debatable whether prophylactic surgery for all patients with asymptomatic severe degenerative MR derives prognostic benefit.
At the other end of the clinical spectrum, the increased operative mortality and worse long term prognosis of symptomatic patients is well proven. Patients with New York Heart Association Class III or IV status have excessive operative mortality and significantly increased mortality at 10 years. Both this study and another have demonstrated that preoperative ejection fraction is an independent predictor of long term survival. Although this evidence base does not support prophylactic surgery on asymptomatic patients, it does highlight the importance of avoiding the long term sequelae of MR in causing symptomatic status or left ventricular impairment. Hence attention has turned to objective markers or investigations independent of symptomatic status that may be subjectively assessed in the early phases; to help identify patients who would prognostically benefit from earlier surgical intervention.
In summary, severe mitral regurgitation is a common valvular pathology that causes a significant burden of disease. Current guidelines for timing of operative intervention are mostly based on expert opinion rather than randomised trials or studies. The ideal tipping point investigation will be an objective marker of functional capacity which correlates with known surrogates of survival such as left ventricular function; and detects early decline, but returns to normal after successful surgery. The improved evidence base will create an epidemiological shift in patterns of referring for mitral valve surgery and reduce the burden of disease of heart failure.
Patients will undergo the following investigations:
Right heart catheterisation- It is the usual gold standard practice at our institution for patients to have a right heart catheterisation before being referred for surgery. Those who have not had one may be referred to the Department of Cardiology at Hammersmith Hospital for this test.
Cardiac MRI- patients will have a T1 weighted cardiac MRI. One strength of cardiac MRI over transthoracic echocardiogram is objective measurements of right heart function. Parameters measured will be ventricular ejection fraction and dimensions, patterns of myocardial fibrosis.
Cardiopulmonary exercise testing (CPEX)- CPEX is a quantitative and validated method of assessing cardiorespiratory function and exercise capacity with commonly measured variables including maximal oxygen consumption (VO2 max) and the clearance of carbon dioxide during exercise (Ve/VCO2). The patient's gaseous exchange is monitored during a 3 minute rest period, a three minute "rolling basal" period when they perform exercise on a bicycle with no load; and subsequently during the exercise phase when the work load increases at a rate of 30 Watts per minute. Exercise continues until the patient has to stop or achieves predicted maximum heart rate.
Pulmonary function tests- Patients will have routine spirometry tests and also assessment of transfer factor.
Transthoracic echocardiogram- It is normal practice for patients to have an echocardiogram at preassessment clinic to assess biventricular function, dimensions and cardiac structural disease.
Quality of life questionnaire- Patients will be asked to fill out a validated questionnaire (SF-36 health survey).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | – | Diagnostic Test: Cardiac catheterisation, Diagnostic Test: Cardiopulmonary exercise testing, Diagnostic Test: Pulmonary function tests, Diagnostic Test: Cardiac MRI, Other: Quality of life survey, Procedure: Mitral valve operation, Procedure: Myocardial biopsiesAsymptomatic/mild symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction >60%) |
| B | – | Diagnostic Test: Cardiac catheterisation, Diagnostic Test: Cardiopulmonary exercise testing, Diagnostic Test: Pulmonary function tests, Diagnostic Test: Cardiac MRI, Other: Quality of life survey, Procedure: Mitral valve operation, Procedure: Myocardial biopsiesSymptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction greater than or equal to 60%) |
| C | – | Diagnostic Test: Cardiac catheterisation, Diagnostic Test: Cardiopulmonary exercise testing, Diagnostic Test: Pulmonary function tests, Diagnostic Test: Cardiac MRI, Other: Quality of life survey, Procedure: Mitral valve operation, Procedure: Myocardial biopsiesPatients with impaired pre-operative left ventricular function (defined as left ventricular ejection fraction <60%) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing cardiac surgery for severe primary/degenerative mitral regurgitation under the current guidelines.
Key inclusion criteria (1 listed)
- Patients listed for surgery for severe primary mitral regurgitation +/- concomitant coronary artery bypass grafting for bystander disease +/- tricuspid valve surgery +/- atrial fibrillation surgery.
Key exclusion criteria (2 listed)
- Secondary mitral regurgitation. Significant history of ischaemic heart disease eg. angina. Age <18 years or >85 years. Critical preoperative status with multi-organ dysfunction. Emergency cardiac surgical intervention. Pregnancy. Unable to give informed consent or unwilling to participate in research. Patients with definite contraindication for MRI would be excluded from the cardiac MRI element of the study.
- Patients we are unable to take adequate biopsies due to technical difficulties would be excluded from the myocardial biopsy element of 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 catheterisationPre-operative left heart catheterisation +/- right heart catheterisation | Diagnostic test | A, B, C |
| Cardiopulmonary exercise testingPre and post-operative cardiopulmonary exercise testing | Diagnostic test | A, B, C |
| Pulmonary function testsPre and post-operative pulmonary function tests | Diagnostic test | A, B, C |
| Cardiac MRIPre and post-operative cardiac MRI | Diagnostic test | A, B, C |
| Quality of life surveyPre and post-operative quality of life survey (SF36) | Other | A, B, C |
| Mitral valve operationClinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery | Procedure or surgery | A, B, C |
| Myocardial biopsiesRight and left epicardial ventricular biopsies taken at time of clinically indicated surgery | Procedure or surgery | A, B, C |
Primary outcome
Impaired Post-operative Functional Capacity
Time frame: 1 year
Dichotomic variable of post-operative left ventricular ejection < 50% and/or post-operative percentage predicted peak VO2 <= 84%
Imaging Data
Time frame: 1 year
Correlation between transthoracic echocardiogram and cardiac MRI parameters
3 secondary outcomes
Right Heart Catheterisation
Time frame: Pre-op
Quality of Life as Assessed by SF36 Survey
Time frame: Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)
Myocardial Histology
Time frame: At surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40424530Afoke J, Gibbs S, Kanaganayagam S, Bruno D, Howard L, Punjabi P. Changes in cardiopulmonary exercise testing variables after surgery for primary mitral regurgitation. Perfusion. 2026 Mar;41(2):165-172. doi: 10.1177/02676591251346035. Epub 2025 May 27.
- Individual participant dataSharing planned: No
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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.
Prakash Punjabi, FRCS principal investigator
Imperial College London
Simon Gibbs, FRCP principal investigator
Imperial College London
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 Regurgitation and Pulmonary Hypertension, run by Imperial 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 2 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 28 Feb 2023. 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?
Yes. Results are posted in the registry (first posted 28 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Impaired Post-operative Functional Capacity (time frame: 1 year). 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 NCT03155373, 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 28 Feb 2023.