Projet

Early Markers of Cardiovascular Remodeling in Valvulopathy and Heart Failure

Cardiovascular diseases remain the first cause of death in industrialized countries, and given the aging population, they represent a major societal challenge. Prevalence of cardiovascular and degenerative diseases (in particular aortic stenosis and heart failure) are steadily increasing related to an aging population [aortic sclerosis and aortic stenosis estimated at 25% and 5% in patients older than 75 year-old, respectively; heart failure estimated at 2%, also increasing in elderly patients (10%)] and have significant medical and economic impacts (hospitalizations, treatments, etc.). On the other hand, aortic stenosis remains incompletely elucidated and so far no treatment has demonstrated a beneficial effect in this pathology. Surgical or percutaneous aortic valve replacement is only proposed at a late stage although aortic stenosis is easily identifiable at the early stage of aortic sclerosis. Finally, no new therapeutic class has been proposed in the past decade in the management of heart failure.

Early vascular alterations, particularly endothelial dysfunction and arterial calcification, play a major role in the development, progression and worsening of cardiovascular diseases through a continuous remodeling process, especially in the field of aortic stenosis and heart failure.

However, this link remains unclear, and the characterization and identification of new early markers in this context is of paramount importance, and requires an approach that takes into account the full continuum of development of these pathologies from the earliest phases (arterial alterations, aortic sclerosis) to the latest events (heart failure, aortic stenosis).

Objectives:

The aim of this project is to identify new diagnostic and prognostic markers (biological and/or imaging biomarkers) of early cardiovascular remodeling leading to aortic stenosis and heart failure with two aspects:

  1. A cognitive aspect, aiming to improve our understanding of the mechanisms of early vascular and valvular alterations that will lead to end-stage valvular diseases (aortic stenosis) and heart failure. This cognitive aspect will particularly focus on endothelial alterations and arterial calcification, and should lead to identify new diagnostic and prognostic markers of early cardiovascular remodeling.
  2. A therapeutic aspect: with the objective of improving the management of valvular disease and heart failure in their early stages. This part of the project will aim to identify new therapeutic approaches capable to slow down progression of vascular and valvular alterations.

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