Valve Heart DiseasesDIFFUsENCT02747485
Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases ( The DIFFUsE Study)
A study testing Cardiac MRI, blood samples and myocardial biopsy in people with Valve Heart Diseases, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Valve Heart Diseases
- What is being tested?
- Cardiac MRI, blood samples and myocardial biopsy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 1 siteFrance
- Study dates
- May 2016to Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance Publique Hopitaux de Marseille
Marseille, Bouche DU Rhone, 13354
About this study
Official title: 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.
- Conditions
- Valve Heart Diseases
- Being tested
- Cardiac MRI, blood samples, myocardial biopsy
- Medical subject headings
- Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac MRIDevice
blood samplesBiological
Serum levels of biomarkers of myocardial fibrosis (galectine-3 and ST2) will be measured
myocardial biopsyProcedure or surgery
blood samplesGenetic
extract DNA to look for genomic mutations associated with the disease.
| Study group | Role | What they receive |
|---|---|---|
| organic left-sided regurgitant valve | Experimental | Not described Receives: Device: Cardiac MRI; Biological: blood samples; Procedure: myocardial biopsy; Genetic: blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rate of diffuse myocardial fibrosis
Measured: 6 months
Secondary outcomes (4)
Correlations between ECV and the global longitudinal strain and the serum level of Galectin-3 and ST2
Measured: 42 months
Correlations between ECV changes and genetic factors
Measured: 42 months
correlations between ECV and the severity of the regurgitation
Measured: 42 months
correlation between ECV and the myocardial deformation quantified by speckle tracking echocardiography (2D Strain)
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2016 (estimated)
- Study startMay 2016
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Valve Heart DiseasesStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine GEINDRE, Study director, Assistance Publique Hopitaux De Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02747485
- Sponsor's protocol ID
- 2016-11
- Other IDs
- 2015-A00587-42
- Acronym
- DIFFUsE
- Status last verified
- May 2026
- First submitted
- 19 Apr 2016
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases " The DIFFUsE Study "
- ClinicalTrials.gov ID
- NCT02747485
- Acronym / sponsor ID
- DIFFUsE / 2016-11
- Conditions
- Valve Heart Diseases
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 316 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 21 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| organic left-sided regurgitant valve | Experimental | Device: Cardiac MRI, Biological: blood samples, Procedure: myocardial biopsy, Genetic: blood samples |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- Age < 18 years
- Pregnancy
- Impossibility to maintain a decubitus position
- Arrhythmia that do not allow an ECG synchronization during MRI
- Hemodynamic instability
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac MRI | Device | organic left-sided regurgitant valve |
| blood samplesSerum levels of biomarkers of myocardial fibrosis (galectine-3 and ST2) will be measured | Biological | organic left-sided regurgitant valve |
| myocardial biopsy | Procedure or surgery | organic left-sided regurgitant valve |
| blood samplesextract DNA to look for genomic mutations associated with the disease. | Genetic | organic left-sided regurgitant valve |
Primary outcome
the rate of diffuse myocardial fibrosis
Time frame: 6 months
4 secondary outcomes
Correlations between ECV and the global longitudinal strain and the serum level of Galectin-3 and ST2
Time frame: 42 months
Correlations between ECV changes and genetic factors
Time frame: 42 months
correlations between ECV and the severity of the regurgitation
Time frame: 42 months
correlation between ECV and the myocardial deformation quantified by speckle tracking echocardiography (2D Strain)
Time frame: 42 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine GEINDRE study director
Assistance Publique Hopitaux De Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiac MRI, blood samples and myocardial biopsy in people with Valve Heart Diseases, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the rate of diffuse myocardial fibrosis (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.