Valve Heart Diseases Clinical Trial
Official title:
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.
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