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

NCT ID: NCT02747485

Last Updated: 2019-03-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2020-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

organic left-sided regurgitant valve

Group Type: EXPERIMENTAL

Cardiac MRI

Intervention Type: DEVICE

blood samples

Intervention Type: BIOLOGICAL

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

myocardial biopsy

Intervention Type: PROCEDURE

blood samples

Intervention Type: GENETIC

extract DNA to look for genomic mutations associated with the disease.

Interventions

Cardiac MRI

Intervention Type: DEVICE

blood samples

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

Intervention Type: BIOLOGICAL

myocardial biopsy

Intervention Type: PROCEDURE

blood samples

extract DNA to look for genomic mutations associated with the disease.

Intervention Type: GENETIC

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine GEINDRE

Role: STUDY_DIRECTOR

Assistance Publique Hopitaux De Marseille

Locations

Assistance Publique Hopitaux de Marseille

Marseille, Bouche DU Rhone, France

Site Status: RECRUITING

Countries

France

Central Contacts

THUNY franck, PU PH

Role: CONTACT

franck.thuny@ap-hm.fr

AVIERINOS Jean-Francois, PU PH

Role: CONTACT

jfavierinos@ap-hm.fr

Facility Contacts

THUNY FRANCK

Role: primary

franck.thuny@ap-hm.fr

AVIERINOS JEAN-FRANCOIS

Role: backup

jfavierinos@ap-hm.fr

Other Identifiers

2015-A00587-42

Identifier Type: OTHER

Identifier Source: secondary_id

2016-11

Identifier Type: -

Identifier Source: org_study_id