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

March 4, 2019 updated by: Assistance Publique Hopitaux De Marseille

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

316

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
the rate of diffuse myocardial fibrosis
Time Frame: 6 months
6 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique Hopitaux De Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2016

Primary Completion (ANTICIPATED)

August 1, 2020

Study Completion (ANTICIPATED)

December 1, 2020

Study Registration Dates

First Submitted

April 19, 2016

First Submitted That Met QC Criteria

April 20, 2016

First Posted (ESTIMATE)

April 21, 2016

Study Record Updates

Last Update Posted (ACTUAL)

March 7, 2019

Last Update Submitted That Met QC Criteria

March 4, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-11
  • 2015-A00587-42 (OTHER: ansm)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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