Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases ( The DIFFUsE Study) (DIFFUsE)
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|ClinicalTrials.gov Identifier: NCT02747485|
Recruitment Status : Recruiting
First Posted : April 21, 2016
Last Update Posted : March 7, 2019
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||316 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|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.
- the rate of diffuse myocardial fibrosis [ Time Frame: 6 months ]
- 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 ]
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
|Contact: THUNY franck, PU PHemail@example.com|
|Contact: AVIERINOS Jean-Francois, PU PHfirstname.lastname@example.org|
|Assistance Publique Hopitaux de Marseille||Recruiting|
|Marseille, Bouche DU Rhone, France, 13354|
|Contact: THUNY FRANCK email@example.com|
|Contact: AVIERINOS JEAN-FRANCOIS firstname.lastname@example.org|
|Study Director:||Catherine GEINDRE||Assistance Publique Hopitaux De Marseille|