Natural History of Mild and of Moderate Aortic Stenosis—New Insights From a Large Prospective European Study Christa Gohlke-Ba ¨ rwolf, MD, Jan Minners, MD, PhD, Nikolaus Jander, MD, Eva Gerdts, MD, PhD, Kristian Wachtell, MD, PhD, Simon Ray, MD, and Terje R. Pedersen, MD, PhD Abstract: Increased life expectancy has led to a higher prevalence of calcific aortic valve disease. Both ends of the disease spectrum—sclerosis of the aortic valve with- out hemodynamic obstruction and the late stage of aortic valve stenosis (AS)—have been associated with increased morbidity and mortality. This raises the question of the prognostic contribution of atherosclerotic diseases and other comorbidities as opposed to the hemodynamic effect of obstructive AS. Hence, the evaluation of asymptomatic patients with mild or moderate AS without comorbidities is of major interest. In the Simvastatin and Ezetimibe in Aortic Stenosis study, with the exception of hypertension, comorbidities were excluded, thus allowing an analysis of the effect of pure AS as well as the effect of hypertension on the progression and outcome of AS. Curr Probl Cardiol 2013;38:365–409. 0146-2806/$ – see front matter http://dx.doi.org/10.1016/j.cpcardiol.2013.06.003 Christa Gohlke-Bärwolf received lecture fees, travel expenses and payment as member of the scientific committee of the SEAS study from Merck/Schering-Plough Pharmaceuticals, North Wales. Jan Minners received payment for travel/accommodation/meeting expenses from Merck/Schering-Plough Pharmaceuticals, North Wales. Nikolaus Jander received payment for developments of educational presentations from Kardiologiefo- rum Schweiz, Rheinfelden, Switzerland; Institut für Kardiovaskuläre Fort- und Weiterbildung e.V, Bad Krozingen, Germany; Interdisziplinäres Trainings- und Simulationszentrum, Würzburg, Germany; Universitätsklinik Freiburg, Germany; mediCORum GmbH, Pforzheim, Germany; payment for travel/accommodation/meeting expenses from Boehringer Ingelheim Pharma GmbH, Germany; and Merck/Schering-Plough Pharmaceuticals, North Wales. Eva Gerdts received consulting fees and her institution a grant from Merck/Schering-Plough Pharmaceuticals, North Wales. Kristian Wachtell Kristian Wachtell’s institution received payment for grant, consultant fee and as member of the scientific committee of the SEAS study from Merck/Schering-Plough Pharmaceuticals, North Wales. Simon Ray received payment for travel/accommodation/meeting expenses from Merck/Schering-Plough Pharmaceuticals, North Wales. Terje R. Pedersen received research grants from Merck and Pfizer, consultation fees from Merck AztraZeneca, Pfizer, and Amgen, speakers honoraria from Merck, Pfizer, AstraZeneca, Roche, Novartis and GlaxoSmithKline. Curr Probl Cardiol, September 2013 365