Studio clinico-patologico integrato della Malattia Degenerativa Valvolare Aortica, attraverso i principali marcatori isto-plasmatici di rimodellamento, aterosclerosi e flogosi

Abstract Objectives. To assess the pathophysiological, prognostic role of Aortic Regurgitation (AR) in the “mixed pictures” of Degenerative Aortic Valve Steno-Insufficiency (ASI), by a multimarker clinical approach. Methods. We enrolled 112 consecutive surgical patients: 19 with pure valve stenosis (PAS); 39 with mild regurgitation (m-ASI), 29 with severe regurgitation (s-ASI); 25 controls with anulo-ectasic regurgitation (AR). All underwent complete echocardiography, carotid ultrasound and aortic/coronary Multislice Computed Tomography (MSCT) calcium score. We determined: tissue semi-quantitative Osteopontin (OPN), Metalloproteinases (MMPs), MMP inhibitors (TIMPs) and circulating brain natriuretic peptide (BNP), TIMPs, MMPs, OPN. We evaluated major adverse cardiac events (MACE) and cardiovascular early, longterm mortality after bioprosthetic valve implantation. Results. Tissue calcification, carotid and coronary atherosclerotic disease were prevalent in PAS vs ASI and AR. MSCT calcium score (Agatson) was comparable between PAS and ASI (PAS: 3.507.3+2442.6, m-ASI: 4.270.7+2213.5, s-ASI: 3.568.5+1823.4), much lower in AR (1247.8+2708.6). In ASI, prevailed a plasma/tissue “profibrotic” MMPs/TIMPs balance, with circulating and echocardiographic indices of myocardial dysfunction. Percentages of MACE, early, longterm mortality were higher in ASI. Conclusions. In ASI, different, still unknown, genetic and dysplastic factors could work synergically with cardiovascular risk factors, determining a much more adverse myocardial and valve remodeling, resulting in a worse clinical outcome.