Calcific aoric valve disease (CAVD) is extremely common worldwide, affecting almost 50% of the population over 85 years of age, with a lethality higher than 50% at 2 years for symptomatic patients, unless aortic-valve replacement is performed. CAVD is characterized by slowly progressive fibro-calcific remodelling of the valve leaflets causing aortic stenosis. The spectrum of the disease progression starts with leaflet degeneration and progresses from early lesions to valve stenosis/obstruction, which is initially mild to moderate but eventually becomes severe. Risk factors for CAVD partly overlap those for atherosclerosis but also intake age-related tissue changes and effects of comorbiditiies (e.g. renal failure) in the overall complex mechanisms of valve leaflet degeneration, which is, at present, unpreventable, leaving aortic valve repair the only treatment option for severe aortic stenosis. In the first phase of the disease the valve becomes thickened and mildly calcified, then the disease evolves to severe valve calcification with impaired leaflet motion and vast blood flow obstruction. Calcific AS valves show advanced osteogenic metaplasia with the presence of osteoblast-like cells and chondrocytes associated with dense inflammatory infiltrates. Bacteria have been detected in the absence of diagnosis of acute infective endocarditis, but their role is still unknown. Different bacterial species (C. acnes (59%), E. faecalis (16%), S. aureus (15%), and S. pyogenes (10%)) have been typed and intramural bacterial colonization has been observed in patients with calcified structural valvular heart disease. Indeed, it has been recently demonstrated that bacterial infections can directly affect osteoblast differentiation/activation. The Authors hypothesized that a subclinical or latent valvular bacterial infiltration facilitates a chronic inflammation and contributes to accelerated structural valve degeneration. An interdisciplinary team has been established to investigate the infective, biochemical and structural features of calcific aortic valve disease.