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

NCT02747485 | Active Not Recruiting

• 2 other identifiers: 2016-112015-A00587-42
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 1

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.

Conditions

Valve Heart Diseases

Outcome Measures

Primary Outcomes (1)

• the rate of diffuse myocardial fibrosis

  6 months

Secondary Outcomes (4)

• Correlations between ECV and the global longitudinal strain and the serum level of Galectin-3 and ST2

  42 months

• Correlations between ECV changes and genetic factors

  42 months

• correlations between ECV and the severity of the regurgitation

  42 months

• correlation between ECV and the myocardial deformation quantified by speckle tracking echocardiography (2D Strain)

  42 months

Study Arms (1)

organic left-sided regurgitant valve

EXPERIMENTAL

Device: Cardiac MRI; Biological: blood samples; Procedure: myocardial biopsy; Genetic: blood samples

Interventions

Cardiac MRI DEVICE

organic left-sided regurgitant valve

blood samples BIOLOGICAL

Serum levels of biomarkers of myocardial fibrosis (galectine-3 and ST2) will be measured

organic left-sided regurgitant valve

myocardial biopsy PROCEDURE

organic left-sided regurgitant valve

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hopitaux de Marseille

Marseille, Bouche DU Rhone, 13354, France

Location

MeSH Terms

Conditions

Heart Valve Diseases

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Catherine GEINDRE

  Assistance Publique Hopitaux De Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: April 21, 2016
• Study Start: May 1, 2016
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

FR (1)