The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation
The Role of Myocardial Fibrosis 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.
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.
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.