The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation

University Hospital Birmingham NHS Foundation Trust

Status: Completed

Conditions: Mitral Valve Regurgitation; Mitral Regurgitation

Treatments: Procedure: Mitral valve repair

Study type: Observational

Funder types: Other

Identifiers

NCT02355418

Not yet available

Details and patient eligibility

About

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.

Full 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.

Enrollment: 147 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

147 participants in 2 patient groups

Patients for early surgery

Description:

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.

Treatment:

Procedure: Mitral valve repair

Patients against early surgery

Description:

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.