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

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.

Study Overview

• Status: Recruiting
• Conditions: Severe Mitral Regurgitation
• Intervention / Treatment: Diagnostic test: Cardiac magnetic resonance imaging before the procedure; Procedure: Transcatheter mitral edge-to-edge repair.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christoph MD Gräni, PHD; Phone Number: +41 31 632 4508; Email: christoph.graeni@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Cardiology, University Hospital Bern, Inselspital, Bern
    • Contact: Christoph Gräni, Prof; Phone Number: +41316324508; Email: christoph.graeni@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: University Hospital, Basel, Switzerland; Cardiocentro Ticino; Triemli Hospital
• Investigators: Principal Investigator: Christoph MD Gräni, PHD, Department of Cardiology, University Hospital Bern, Inselspital, Bern

Publications and helpful links

General Publications

• Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Weissman NJ, Mack MJ; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23.
• Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, Lefevre T, Piot C, Rouleau F, Carrie D, Nejjari M, Ohlmann P, Leclercq F, Saint Etienne C, Teiger E, Leroux L, Karam N, Michel N, Gilard M, Donal E, Trochu JN, Cormier B, Armoiry X, Boutitie F, Maucort-Boulch D, Barnel C, Samson G, Guerin P, Vahanian A, Mewton N; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018 Dec 13;379(24):2297-2306. doi: 10.1056/NEJMoa1805374. Epub 2018 Aug 27.
• Praz F, Grasso C, Taramasso M, Baumbach A, Piazza N, Tamburino C, Windecker S, Maisano F, Prendergast B. Mitral regurgitation in heart failure: time for a rethink. Eur Heart J. 2019 Jul 14;40(27):2189-2193. doi: 10.1093/eurheartj/ehz222. No abstract available.
• Grani C, Biere L, Eichhorn C, Kaneko K, Agarwal V, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis. Int J Cardiovasc Imaging. 2019 Jun;35(6):1067-1078. doi: 10.1007/s10554-019-01552-6. Epub 2019 Feb 12.
• Grani C, Eichhorn C, Biere L, Kaneko K, Murthy VL, Agarwal V, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis. J Cardiovasc Magn Reson. 2019 Feb 28;21(1):14. doi: 10.1186/s12968-019-0520-0.
• Grani C, Eichhorn C, Biere L, Murthy VL, Agarwal V, Kaneko K, Cuddy S, Aghayev A, Steigner M, Blankstein R, Jerosch-Herold M, Kwong RY. Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis. J Am Coll Cardiol. 2017 Oct 17;70(16):1964-1976. doi: 10.1016/j.jacc.2017.08.050. Erratum In: J Am Coll Cardiol. 2017 Nov 28;70(21):2736. doi: 10.1016/j.jacc.2017.10.042.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Mitral Regurgitation; MitraClip; Cardiac magnet resonance (CMR); Transcatheter mitral edge-to-edge repair; CMR feature tracking; Parametric mapping
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 2021-00704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No