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