The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation

Mitral Regurgitation Clinical Trial

Official title:

A Prospective Observational Study Examining the Role of Myocardial Fibrosis in Outcome Following Mitral Valve Repair in Degenerative Mitral Regurgitation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02355418
• Other study ID #: Not yet available
• Status: Completed
• Start date: September 2015
• Est. completion date: March 2019

Study information

• Verified date: March 2022
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 regurgitation who have the option of choosing surgical repair or watchful waiting.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mitral Regurgitation
• Mitral Valve Insufficiency
• Mitral Valve Regurgitation

Intervention

Procedure:
• Mitral valve repair
Standard mitral valve repair surgery

Locations

Country	Name	City	State
United Kingdom	University Hospital Birmingham	Birmingham	West Midlands

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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