The Quest for a Medical Treatment of Aortic Stenosis: Putative Therapeutic Targets

Aortic stenosis (AS), i.e. calcification and obstruction of the aortic valve (AV), is the most common type of valvular heart disease. The therapeutic options for AS are currently limited to either AV replacement surgery or transcatheter AV implantation. In contrast, no medical treatment has proven effective in slowing the process of valve calcification. The molecular and cellular pathophysiology of AS is an active and complex process, with components of inflammation, lipid accumulation, valvular remodelling, dystrophic calcification, oxidative stress, apoptosis, and heterotopic ossification. These pathways contain several potential targets for medical treatment, which are discussed in the present review. These include the targeting of lipids and lipoproteins, inflammation, and calcification pathways, which have been explored in experimental, epidemiological, and prospective studies. However, further mechanistic studies and prospective trials are needed to better understand the pathophysiology of AS and to lead to new therapeutic strategies for the prevention, or at least the delay, of either surgical or transcatheter valve implantations.