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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02747485
Recruitment Status : Unknown
Verified March 2019 by Assistance Publique Hopitaux De Marseille.
Recruitment status was:  Recruiting
First Posted : April 21, 2016
Last Update Posted : March 7, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille

Study Description
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Brief 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. 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.


Condition or disease Intervention/treatment Phase
Valve Heart Diseases Device: Cardiac MRI Biological: blood samples Procedure: myocardial biopsy Genetic: blood samples Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 316 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases " The DIFFUsE Study "
Actual Study Start Date : May 2016
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. the rate of diffuse myocardial fibrosis [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Correlations between ECV and the global longitudinal strain and the serum level of Galectin-3 and ST2 [ Time Frame: 42 months ]
  2. Correlations between ECV changes and genetic factors [ Time Frame: 42 months ]
  3. correlations between ECV and the severity of the regurgitation [ Time Frame: 42 months ]
  4. correlation between ECV and the myocardial deformation quantified by speckle tracking echocardiography (2D Strain) [ Time Frame: 42 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02747485


Contacts
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Contact: THUNY franck, PU PH franck.thuny@ap-hm.fr
Contact: AVIERINOS Jean-Francois, PU PH jfavierinos@ap-hm.fr

Locations
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France
Assistance Publique Hopitaux de Marseille Recruiting
Marseille, Bouche DU Rhone, France, 13354
Contact: THUNY FRANCK       franck.thuny@ap-hm.fr   
Contact: AVIERINOS JEAN-FRANCOIS       jfavierinos@ap-hm.fr   
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
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Study Director: Catherine GEINDRE Assistance Publique Hopitaux De Marseille
More Information
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Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT02747485    
Other Study ID Numbers: 2016-11
2015-A00587-42 ( Other Identifier: ansm )
First Posted: April 21, 2016    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Heart Diseases
Heart Valve Diseases
Cardiovascular Diseases