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, Christopher Weston, Gerard Nash, Nicolas Nikolaidis, Thomas Barker, Ramesh Patel, Moninder Bhabra, Richard P Steeds, Boyang Liu, Nicola C Edwards, Desley A H Neal, Christopher Weston, Gerard Nash, Nicolas Nikolaidis, Thomas Barker, Ramesh Patel, Moninder Bhabra, Richard P Steeds

Abstract

Background: The optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve but identification of the optimal timing of surgery remains challenging. Current guidelines suggest 'watchful waiting' until the onset of symptoms or left ventricular (LV) dysfunction but these have been challenged as promoting 'rescue surgery'. Better predictors are required to inform decision-making in relation to the necessity and timing of surgery. Chronic volume overload is a stimulus for adverse adaptive LV remodelling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect the development of myocardial fibrosis in response to chronic volume overload. Myocardial fibrosis can be detected non-invasively using cardiac magnetic resonance (CMR) imaging techniques as an expansion of the extracellular volume (ECV).

Methods/design: This study investigates whether: 1) patients with above median ECV will have smaller reduction in end-systolic volume index (as a measure of the degree of reverse LV remodelling) on CMR following mitral valve repair, compared to those with below median ECV; and 2) higher ECV on CMR, validated through histology, adversely impacts upon post-operative complications and symptomatic improvement following surgery. This is a multi-centre, prospective, cross-sectional comparison of patients prior to and 9 months following surgery for chronic severe primary degenerative MR. To establish the natural history of ECV in MR, an additional cohort of patients with asymptomatic MR who do not wish to consider early repair will be followed. Investigations include CMR, cardiopulmonary exercise test, stress echocardiography, signal-averaged electrocardiogram, 24-h electrocardiogram monitoring, laboratory tests and patient-reported outcome measures. Patients undergoing surgery will have cardiac biopsies performed at the time of mitral valve repair for histological quantification of fibrosis.

Discussion: This study will advance our understanding of ventricular remodelling in MR, its impact on patient symptoms and ventricular response following surgery. Establishing the link between myocardial fibrosis (measured on CMR and validated through histology), with early ventricular dysfunction, will offer physicians a novel non-invasive biomarker that can further inform the timing of surgery.

Trial registration: This trial was registered at ClinicalTrials.gov ( NCT02355418 ) on 30th November 2015.

Keywords: Arrhythmia risk; Cardiac MRI; Exercise capacity; Extracellular volume; Myocardial fibrosis; Primary mitral regurgitation; Timing of surgery; Ventricular reverse remodelling.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval for this study was first awarded by University Hospital Birmingham and the NRES Committee East Midlands on 2nd June 2015 (REC reference 15/EM/0243). The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. All study participants will provide written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design flowchart

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