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NCT Number: NCT07066904

Quantification of Mitral Regurgitation Using 4D MRI Flow : Comparison With 2D MRI Flow and Echocardiography Using the Evolution of Left Ventricular Remodeling as a Reference

The goal of this study is to evaluate whether 4D MRI provides a better assessment of mitral regurgitation quantification and associated ventricular remodeling than standard imaging techniques: echocardiography and 2D MRI, in patients suffuring from mitral regurgitation. 4D MRI demonstrated its superiority to 2D MRI in some other valve diseases but remains not widely used, due to a lack of evidence. The main question our study aims to answer is:

• Is mitral regurgitant volume measured on 4D MRI more strongly related to remodeling progression (after correction of regurgitation or not) than regurgitant volume measured on 2D MRI and echocardiography?

Participants will undergo 4D MRI, 2D MRI and echocardiography twice at six-month intervals.

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Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Groupe hospitalier Paris Saint-Joseph - hôpital Marie-Lannelongue, Le Plessis-Robinson, France

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About this study

Mitral Regurgitation (MR) is a widely prevalent valvular disease. The decision to refer patients for intervention relies on the precise quantification of MR using the mitral regurgitant volume. This quantification is primarily performed through transthoracic echocardiography (TTE), but its accuracy is limited by operator dependency and acoustic windows.

Magnetic resonance imaging (MRI) is now considered the preferred alternative technique for measuring mitral regurgitant volume using 2D phase-contrast sequences. However, it requires significant expertise from specialized centers.

4D flow MRI enables the recording of blood flow velocities in all directions across the entire cardiac volume and has demonstrated superiority over 2D MRI in other valvular diseases. However, limited data are available for validating the estimation of mitral regurgitation using 4DFlow-MRI, mainly due to the absence of a reference technique. As previously proposed for comparisons between 2D MRI and TTE, ventricular remodeling progression will be used as the evaluation criterion.

Primary Objective:

The main goal is to demonstrate that mitral regurgitant volume assessed by 4DFlow-MRI is more strongly correlated with left ventricular (LV) remodeling progression after correction or persistence of MR than mitral regurgitant volume assessed by 2D MRI or TTE, after adjustment for residual MR.

The primary outcome criterion will be the analysis of the association between the absolute change in LV end-diastolic volume (LVEDV) between baseline (M0) and 6 months after (M6) and mitral regurgitant volume at M0, as calculated by the different methods or MR severity estimated using the integrative TTE approach, adjusted for residual MR.

Secondary Objectives:

  • Evaluate the association between LV remodeling and mitral regurgitant volume measured by the different methods in the subgroup of patients undergoing percutaneous intervention, where correction is incomplete and residual MR assessment is challenging.
  • Evaluate the association between LV remodeling and mitral regurgitant volume measured by the different methods in the subgroup of patients undergoing surgical intervention, where correction is expected to be excellent with no residual MR.
  • Analyze the determinants of LV remodeling progression using novel volumetric echocardiography methods, including specific ultrafast ultrasound sequences, allowing comparisons with data from the most innovative echocardiographic techniques.
  • Investigate all determinants of LV remodeling progression at six months beyond mitral regurgitant volume, including the significance of LV remodeling, longitudinal strains of the LV and left atrium (assessed by MRI and TTE), and myocardial fibrosis derived from myocardial T1 mapping before and after gadolinium injection at M0.

Secondary Outcomes Criteria:

  • Primary evaluation criterion assessed in the subgroup of patients who underwent percutaneous MR correction.
  • Primary evaluation criterion assessed in the subgroup of patients who underwent surgical MR correction, disregarding residual MR.
  • Primary evaluation criterion assessed using innovative echographic techniques, including specific ultrafast ultrasound sequences, and compared with the standard TTE, 2D MRI and 4D MRI.
  • Changes in LV remodeling between M0 and M6, based on various indices (LVEDV, fibrosis indices, strain at M0).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Subjects

  • from 18 to 85 years old
  • having signed a consent form to participate in the study
  • suffering from mild, moderate or severe mitral regurgitation based on an ultrasound graduation
  • able to undergo echocardiography and IRM within 7 days after recruitment and then at 6 months

Exclusion criteria

Subjects

  • suffering from aortic regurgitation or stenosis or mitral stenosis associated with more than moderate MR, intracardiac shunting or hypertrophic cardiomyopathy
  • suffering from secondary MR
  • having a contraindication to gadolinium-based contrast agent
  • having a pacemaker, defibrillator or any other contraindication to MRI
  • suffering from renal disease with an eGFR CKD-EPI < 30 ml/min
  • pregnant or breastfeeding
  • under legal protection

Enrolled subjects:

  • with an incomplete or suboptimal ultrasound or MRI examination
  • who have not attended to the 6-month follow-up visit
  • with an intercurrent medical event

will be excluded.

Treatment and study plan

Standard echocardiography

Diagnostic Test

Routine ultrasound examination with standardized recordings for the study, incorporating volumetric assessment techniques

Other names: Cardiac echography, TTE, Heart ultrasounds

2D phase-contrast magnetic resonance imaging

Diagnostic Test

A cardiac MRI will be performed on a 1.5 Tesla system, including a biventricular function study with a series of short-axis slices, three long-axis slices, a 2D phase-contrast acquisition orthogonal to the aortic root. Additionally, standard T1 mapping sequences will be acquired on three short-axis slices, 15 minutes after the injection of 0.2 mmol/kg of body weight of gadolinium, for myocardial and blood T1 measurements.

Other names: 2D MRI, Cardiac magnetic resonance imaging, CMR

4D flow magnetic resonance imaging

Diagnostic Test

A sagittal 4D flow acquisition lasting between 6 and 10 minutes of free breathing to cover all four cardiac chambers is added to the 2D acquisition.

Other names: 4D MRI

Cardiac ultrafast ultrasound imaging

Diagnostic Test

Ultrafast sequences are added to the standard echocardiography acquisition.

Other names: ultrafast echocardiography

Primary outcomes

  1. Absolute change in left ventricle end-diastolic volume

    Time frame: Baseline, 6 months

    The primary outcome criterion will be the analysis of the association between the absolute change in LV end-diastolic volume (LVEDV) between baseline (M0) and 6 months after (M6) and mitral regurgitant volume at M0, as calculated by the different methods or MR severity estimated using the integrative TTE approach, adjusted for residual MR.

  2. Mitral regurgitant volume

    Time frame: Baseline

    The primary outcome criterion will be the analysis of the association between the absolute change in LV end-diastolic volume (LVEDV) between baseline (M0) and 6 months after (M6) and mitral regurgitant volume at M0, as calculated by the different methods or MR severity estimated using the integrative TTE approach, adjusted for residual MR.

Secondary outcomes

  1. Absolute change in left ventricle end-diastolic volume

    Time frame: Baseline, 6 months

    Same outcome as the primary outcome but in a subgroup of patients who have undergone percutaneous mitral regurgitation correction.

  2. Mitral regurgitant volume

    Time frame: Baseline

    Same outcome as the primary outcome but in a subgroup of patients who have undergone percutaneous mitral regurgitation correction.

  3. Absolute change in left ventricle end-diastolic volume

    Time frame: Baseline, 6 months

    Same outcome as the primary outcome but in a subgroup of patients who have undergone surgical mitral regurgitation correction.

  4. Mitral regurgitant volume

    Time frame: Baseline

    Same outcome as the primary outcome but in a subgroup of patients who have undergone surgical mitral regurgitation correction.

  5. Absolute change in left ventricle end-diastolic volume

    Time frame: Baseline, 6 months

    Same outcome as the primary outcome but mesured using ultrafast ultrasound imaging compared to the 3 other imaging techniques performed in the study.

  6. Mitral regurgitant volume

    Time frame: Baseline

    Same outcome as the primary outcome but mesured using ultrafast ultrasound imaging compared to the 3 other imaging techniques performed in the study.

  7. Change from baseline in left ventricle remodeling

    Time frame: Baseline, 6 months

Study contacts

Contact information is provided by the study sponsor or research team.

Maxime Brussieux

CONTACT

[email protected]

+33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • GIRCI IDF
  • Ministry of Health, France

Registry information

Acronym: FLAME

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jul 15, 2025
Registry last updated
Jul 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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