Official Title
Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases " The DIFFUsE Study "
Brief Title
Impact of Diffuse Myocardial Fibrosis on the Ventricular Function in Regurgitant Left-Sided Valve Heart Diseases ( The DIFFUsE Study)
Protocol ID
NCT02747485
Lead Sponsor
Assistance Publique Hopitaux De Marseille
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.
Enrollment Count
316 participants
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
Filters
Valve Heart Diseases
NA
UNKNOWN
ADULT
OLDER_ADULT