Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair

Study Overview
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Brief Summary
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The investigators' hypothesis is that CMR tissue characterization and myocardial function analysis acquired by CMR feature tracking technique predict reverse remodeling in patients with severe secondary mitral regurgitation (MR) undergoing transcatheter mitral edge-to-edge repair.

Detailed Description
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Diametrically opposed results of the COAPT- and the MITRA-FR trial have demonstrated the need for additional evidence in the field of transcatheter mitral edge-to-edge repair. Reverse left ventricular remodeling after treatment of severe secondary mitral regurgitation can indicate treatment response and is associated with positive outcomes. However, so far it is reverse remodeling, respectively treatment response is difficult to predict, which complicates patient selection for mitral edge-to-edge repair. Previous studies have shown, that focal (late gadolinium enhancement (LGE)) but not diffuse myocardial fibrosis (T1 mapping and extracellular volume fraction (ECV)) burden quantification using CMR predicts reverse left ventricular remodeling following cardiac resynchronization therapy in patients with heart failure with reduced ejection fraction (HFrEF). On the other hand, myocardial T1 mapping was predictive for beneficial left ventricular remodeling after long-term heart failure therapy. Furthermore, in patients with HFrEF, LGE is associated with clinical outcome and an incremental predictive value to left ventricular dimensions and function. However, as only 1/3 of HFrEF patients show LGE, subtle fibrosis might be missed. Recently the investigators have shown that different novel fibrosis detection techniques (naive T1 mapping, mean ECV and λGd being the delta of pre- and post T1 mapping and ECV calculation) all demonstrated strong association with outcome in patients with heart failure. The investigators' hypothesis is that these markers (CMR tissue characterization and myocardial function analysis acquired by a CMR feature tracking) might also be helpful in predicting reverse remodeling after transcatheter mitral edge-to-edge repair. This project might help to understand the pathophysiology of the disease in patients with secondary mitral regurgitation, improve risk stratification in this clinical setting, and optimize selection of patients who benefit from transcatheter mitral edge-to-edge repair.

Official Title
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Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair

Conditions
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Severe Mitral Regurgitation

Intervention / Treatment
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* Diagnostic Test: Cardiac magnetic resonance imaging before the procedure
* Procedure: Transcatheter mitral edge-to-edge repair.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe secondary MR characterized, according to the European guidelines and recommendations, by a regurgitant volume ≥30 mL/beat or an effective regurgitant orifice ≥20 mm². Symptomatic patients with New York Heart Association Class ≥II. Left ventricular ejection fraction between 15% and 50%. Optimal standard of care therapy for heart failure according to investigator. Not eligible for a mitral surgery intervention according to the Heart Team. Patients who have the ability to understand the requirements of the study and provide written consent/assent to participate and agree to abide by the study requirements. Exclusion Criteria: Participants younger than 18 years Pregnancy or breastfeeding Severe impaired renal function (GFR < 15 ml/min) Patients with untreated severe concomitant valve disease (e.g. severe tricuspid valve regurgitation, aortic stenosis) The patient has a medical condition, serious concurrent illness, or extenuating circumstance that would significantly decrease study compliance, including all prescribed follow-up The patient has contraindications to CMR, including: Implanted non-CMR conditional metallic implants, pacemaker, intracardiac defibrillator, neurostimulator, epicardial pacemaker leads, or any abandoned leads, ferromagnetic aneurysm clip, ferromagnetic halo device, cochlear implants, implanted infusion pumps or severe claustrophobia The patient is clinically unstable or has stage D congestive heart failure or inability to lay flat for 60 minutes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Patients undergoing transcatheter mitral edge-to-edge repair in this single-arm study. | Diagnostic Test: Cardiac magnetic resonance imaging before the procedure<br>* CMR image acquisition with previously mentioned analysis<br>Procedure: Transcatheter mitral edge-to-edge repair.<br>* Included patients will undergo Transcatheter mitral edge-to-edge repair.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with reverse remodeling after 12 months | Defined as ≥10% reduction in left ventricular end-diastolic volume in patients with successful MR reduction to grade 2+ or less 12 months after mitral edge-to-edge repair assessed by echocardiography. | 12 months after mitral edge-to-edge repair | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with procedural and device success | Procedural and device success as defined according to the criteria of the Mitral Valve Academic Research Consortium | 24 months after mitral edge-to-edge repair | 
| Rate of patients with reverse remodeling after 6 and 24 months | Reverse remodeling at 6 and 24 months, defined according to previously mentioned criteria. | 6 and 24 months after mitral edge-to-edge repair | 
| Change of left ventricular sphericity index | Echocardiographic assessment of LV sphericity index measured using the LV short/long axis dimension ratio in the end-diastolic four-chamber apical view. | 6, 12 and 24 months after mitral edge-to-edge repair | 
| Change in NT-proBNP levels | Change in NT-proBNP levels as an indirect sign of changes in left ventricular filling pressure, fibrosis and reverse remodeling will be measured in clinically indicated follow-ups at different time points after the intervention. | 6, 12 and 24 months after mitral edge-to-edge repair | 
| All cause death | Occurence of death from any cause | 6, 12 and 24 months after mitral edge-to-edge repair | 
| Cardiovascular death | Occurence of death from cardiovascular reason | 6, 12 and 24 months after mitral edge-to-edge repair | 
| Rate of patients with heart-failure related hospitalization | Hospitalizations for heart failure within the observation time will be systematically recorded. | 6, 12 and 24 months after mitral edge-to-edge repair | 
| Change in NYHA class | Change in NYHA class ≥ +/- 1 compared to baseline NYHA-class before mitral edge-to-edge repair. | 6, 12 and 24 months after mitral edge-to-edge repair | 
| Change in myocardial strain | Clinically indicated follow-up imaging (CMR) will be analyzed by CMR feature tracking | Within 24 months after mitral edge-to-edge repair | 
| Change in left ventricular ejection fraction | Echocardiographic assessment of left ventricular ejection fraction measured according to biplane Simpson disk summation method. | 6, 12 and 24 months after mitral edge-to-edge repair | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter mitral edge-to-edge repair, MitraClip, CMR feature tracking, Parametric mapping, Cardiac magnet resonance (CMR), Mitral Regurgitation