Project 433568

With aging, the aortic valve calcifies, thus the opening of the valve decreases, blocking the ejection of the blood in the body: this is aortic stenosis. Aortic stenosis is the most common cardiovascular disease in developed countries after coronary artery disease and systemic arterial hypertension. When the stenosis progresses, the heart needs to work harder to eject the blood into the body. This increase in workload leads to heart failure and death without treatment. The only available treatment is to replace the stenosed valve by a prosthesis. There is no medical treatment to slow down the progression of the aortic stenosis. Despite aortic stenosis is perceived as a "men disease", 50% of patients are women. Unfortunately, the vast majority of studies have been performed in men or male animals. Women are often referred later for valve replacement, with more symptoms and worse heart function. We recently demonstrate that, for the same severity of the disease, women have less calcification in their valve but more fibrosis. We also demonstrated that for the same valve disease, women have more fibrosis in the heart. In our mouse model, we also demonstrated that angiotensin-receptor blockers (ARBs) was effective to slow down aortic stenosis progression in female but not in male. This finding was expected given that ARBs protect against fibrotic deposition. This may explain why some previous studies were not able to find an impact of ARBs in aortic stenosis progression. Indeed, studies enroll a vast majority of men. We believe that ARBs will be able to 1) slow down aortic stenosis progression, with more impact in women than in men and 2) reduce fibrosis deposition in the myocardium which will protect heart function. Thus, we propose to realize a randomized control trial comparing ARBs and placebo, in patients with aortic stenosis, to document the impact of the medication on aortic stenosis progression and heart fibrosis and dysfunction.