Clinical trial NCT02355418: The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation
Official title: A Prospective Observational Study Examining the Role of Myocardial Fibrosis in Outcome Following Mitral Valve Repair in Degenerative Mitral Regurgitation.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mitral Valve Regurgitation
Mitral Regurgitation
Lead sponsor: University Hospital Birmingham NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2015-02-04
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Detection of diffuse interstitial fibrosis in patients with chronic severe degenerative mitral regurgitation and evaluation of its functional consequences.
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
state: West Midlands
Study officials:
affiliation: University Hospital Birmingham
name: Richard Steeds
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.