Clinical trial NCT04913727: Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair
Official title: Prediction of Reverse Remodeling and Outcome in Patients With Severe Secondary Mitral Valve Regurgitation Undergoing Transcatheter Edge-to-edge Mitral Valve Repair
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Severe Mitral Regurgitation
Keywords: Cardiac magnet resonance (CMR)
Mitral Regurgitation
Transcatheter mitral edge-to-edge repair
MitraClip
CMR feature tracking
Parametric mapping
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University Hospital, Basel, Switzerland
name: Cardiocentro Ticino
name: Triemli Hospital
First posted: 2021-06-04
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of patients with reverse remodeling after 12 months
timeFrame: 12 months after mitral edge-to-edge repair
Secondary outcomes:
measure: Rate of patients with procedural and device success
timeFrame: 24 months after mitral edge-to-edge repair
measure: Rate of patients with reverse remodeling after 6 and 24 months
timeFrame: 6 and 24 months after mitral edge-to-edge repair
measure: Change of left ventricular sphericity index
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: Change in NT-proBNP levels
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: All cause death
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: Cardiovascular death
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: Rate of patients with heart-failure related hospitalization
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: Change in NYHA class
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
measure: Change in myocardial strain
timeFrame: Within 24 months after mitral edge-to-edge repair
measure: Change in left ventricular ejection fraction
timeFrame: 6, 12 and 24 months after mitral edge-to-edge repair
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Cardiology, University Hospital Bern, Inselspital, Bern
Study officials:
affiliation: Department of Cardiology, University Hospital Bern, Inselspital, Bern
name: Christoph MD Gräni, PHD
role: PRINCIPAL_INVESTIGATOR
References:
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 Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23.
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, 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.
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 available.
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 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.
citation: 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.
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 patients with suspected myocarditis. J Cardiovasc Magn Reson. 2019 Feb 28;21(1):14. doi: 10.1186/s12968-019-0520-0.