The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation

Conditions

Mitral Regurgitation, Mitral Valve Regurgitation

Brief 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.

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.

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.

2021-08-1829 citations

10.1016/j.jcmg.2021.07.007

Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance.

Liu B, Neil DAH, Premchand M, Bhabra M, Patel R, Barker T, Nikolaidis N, Billing JS, Treibel TA, Moon JC, González A, Hodson J, Edwards NC, Steeds RP.

2020-12-1424 citations

10.1186/s12968-020-00674-4

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

Boyang Liu, Nicola C. Edwards, Desley A. H. Neal, Chris J. Weston, Gerard B. Nash et al. (10 authors)

BMC Cardiovascular Disorders2017-11-2210 citations

10.1186/s12872-017-0715-y

Interventions

PROCEDUREMitral valve repair

Standard mitral valve repair surgery

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Detection of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation and evaluation of its functional consequences.	3 years	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.

Countries

United Kingdom

Outcome results

None listed