Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases ( The DIFFUsE Study) (DIFFUsE)

May 18, 2026 updated by: Assistance Publique Hopitaux De Marseille

Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases " The DIFFUsE Study "

New strategies are needed to early detect myocardial involvement in these diseases. Histological studies showed that diffuse fibrosis and cardiomyocyte hypertrophy precede the LV remodelling (dilatation) observed by cardiac imaging. Quantification of LV diffuse myocardial fibrosis using magnetic resonance imaging (MRI) could reach this goal. Recently, contrast enhanced cardiac MRI has been used to measure the extracellular volume fraction (ECV) of the myocardium, and it has been able to detect diffuse myocardial fibrosis. In diseases in which increased collagen deposition enlarges the extra-cellular space, the ECV can act as a fibrosis index. ECV is correlated with the amount of fibrosis measured by histology. Left ventricular overloads induced by regurgitant VHD result in cardiomyocyte hypertrophy and diffuse fibrosis. Other methods can be used to estimate the degree of myocardial fibrosis such as the serum level of galectine-3 or ST2. Moreover, although the pathophysiological mechanisms leading to the occurrence of myocardial fibrosis differ in patients with various cardiac diseases, the cellular effectors of fibrotic remodelling are common and involve similar signalling pathways. At the cellular level, key progression of ventricular hypertrophy is associated with increased cardiomyocytes apoptosis and fibrosis, suggesting that these two processes are responsible for the transition.

To our knowledge, no study has analysed the impact of the rate of myocardial diffuse fibrosis, non-invasively estimated by ECV, in the risk of LV dysfunction during MR and AR, especially after surgery. The measurement of ECV could become an important tool for risk stratification in left-sided regurgitant VHD. Thus, it would provide an early marker of LV myocardial involvement before the occurrence of global remodeling, might help physicians in surgical decision, and would improve prognosis. This is an innovative original project because it uses modern imaging modalities to answer to a crucial question. The clinical implications would be important because this work would modify the international surgical indications of MR and AR in order to finally improve the prognosis of patients with this frequent heart disease. Moreover, investigators will analyze the genetic factors that can influence the myocardial reaction resulting from these regurgitations, which will improve the quality of this work and offer new future perspectives.

Investigators hypothesize that the ECV measurement could be used as an early predictor of LV dysfunction in the left-sided valve regurgitations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
316

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
    • Bouche DU Rhone
      • Marseille, Bouche DU Rhone, France, 13354
        • Assistance Publique Hopitaux de Marseille

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All consecutive patients referred for organic MR and/or AR at least moderate to severe according to the ESC guidelines criteria⁴ will be eligible. The moderate to severe criteria will defined by echocardiography as followed:
  • MR: an effective regurgitant orifice area (EOA) >30mm2 and/or a regurgitant volume (RV) >45mL
  • AR: an EOA >20mm2 and/or a RV >45mL

Exclusion Criteria:

  • Age < 18 years
  • Pregnancy
  • Impossibility to maintain a decubitus position
  • Arrhythmia that do not allow an ECG synchronization during MRI
  • Hemodynamic instability
  • Indication of urgent surgery
  • Known coronary artery disease
  • Severe arterial hypertension
  • Cardiomyopathy
  • Claustrophobia
  • Gadolinium intolerance
  • Implantable medical devices that do allow to perform MRI
  • Severe renal insufficiency with clearance <35 mL/min
  • Vulnerable patients
  • Acute infective endocarditis
  • Aortic dissection
  • Moderate or severe mitral stenosis (mitral area <1.5cm2/m2)
  • Moderate or severe aortic stenosis (aortic area <0.8cm2/m2, or Vmax>3m/s, or mean gradient>30mmHg)
  • Previous cardiac surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: organic left-sided regurgitant valve
Device: Cardiac MRI
Biological: blood samples
Serum levels of biomarkers of myocardial fibrosis (galectine-3 and ST2) will be measured
Procedure: myocardial biopsy
Genetic: blood samples
extract DNA to look for genomic mutations associated with the disease.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
the rate of diffuse myocardial fibrosis
Time Frame: 6 months
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Correlations between ECV and the global longitudinal strain and the serum level of Galectin-3 and ST2
Time Frame: 42 months
42 months
Correlations between ECV changes and genetic factors
Time Frame: 42 months
42 months
correlations between ECV and the severity of the regurgitation
Time Frame: 42 months
42 months
correlation between ECV and the myocardial deformation quantified by speckle tracking echocardiography (2D Strain)
Time Frame: 42 months
42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique Hopitaux De Marseille

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Catherine GEINDRE, Assistance Publique Hopitaux de Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2016

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 19, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2016-11
  • 2015-A00587-42 (Other Identifier: ansm)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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