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

Severe Mitral Regurgitation Clinical Trial

— PRE-MITRA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04913727
• Other study ID #: 2021-00704
• Status: Recruiting
• Phase: N/A
• Start date: August 4, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Christoph MD Gräni, PHD
• Phone: +41 31 632 4508
• Email: christoph.graeni[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mitral Valve Insufficiency
• Severe Mitral Regurgitation

Intervention

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.

Locations

Country	Name	City	State
Switzerland	Department of Cardiology, University Hospital Bern, Inselspital, Bern	Bern

Sponsors (4)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	Cardiocentro Ticino, Triemli Hospital, University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

References & Publications (6)

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 suspect — View Citation

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 — View Citation

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 Myoc — View Citation

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, Bout — View Citation

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 avail — View Citation

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 Patient — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	All cause death	Occurence of death from any cause	6, 12 and 24 months after mitral edge-to-edge repair
Secondary	Cardiovascular death	Occurence of death from cardiovascular reason	6, 12 and 24 months after mitral edge-to-edge repair
Secondary	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
Secondary	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
Secondary	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
Secondary	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