The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation

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.

Study Overview

• Status: Completed
• Conditions: Mitral Regurgitation; Mitral Valve Regurgitation
• Intervention / Treatment: Procedure: Mitral valve repair

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:

1. identify whether diffuse interstitial myocardial fibrosis impacts upon post-operative complications, symptomatic improvement and ventricular recovery following surgery,
2. to show that diffuse fibrosis (assessed by T1 mapping CMR) is validated by histological assessment on myocardial biopsy,
3. 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 Type: Observational
• Enrollment (Actual): 147

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • University Hospital Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

(1) 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).

Exclusion Criteria:

1. symptoms due to severe MR;
2. LV endsystolic diameter >45mm at baseline;
3. LV ejection fraction <60%;
4. history of myocardial infarction, previous coronary artery bypass graft, or valve surgery;
5. inherited or acquired cardiomyopathy;
6. congenital heart disease; including common atrio-ventricular canal defects;
7. more than mild coexisting aortic valve stenosis or regurgitation
8. primary mitral regurgitation not due to degenerative disease, including rheumatic disease and infective endocarditis;
9. uncontrolled atrial fibrillation (resting HR>100/min average on 24 hour Holter );
10. unable to undergo CMR;
11. unable to walk on treadmill or use supine bicycle.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Procedure: Mitral valve repair; Standard mitral valve repair 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 years

Collaborators and Investigators

• Sponsor: University Hospital Birmingham NHS Foundation Trust
• Collaborators: British Heart Foundation
• Investigators: Principal Investigator: Richard Steeds, University Hospital Birmingham

Publications and helpful links

General 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.
• Liu 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.
• Liu 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): March 1, 2019
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: January 30, 2015
• First Posted (ESTIMATE): February 4, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: not yet available (not yet available)