CLINICAL STATEMENTS AND GUIDELINES 14. Moura LM, Ramos SF, Zamorano JL, et al. Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis. J Am Coll Cardiol. 2007;49:554 61. 15. Rajamannan NM, Evans FJ, Aikawa E, et al. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease 2011 update. Circulation. 2011;124:1783 91. 16. Hansson NH, Sorensen J, Harms HJ, et al. Metoprolol reduces hemody- namic and metabolic overload in asymptomatic aortic valve stenosis pa- tients: a randomized trial. Circ Cardiovasc Imaging. 2017;10:e006557. 17. Lindman BR, Zajarias A, Madrazo JA, et al. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricu- lar function in patients with severe symptomatic aortic stenosis. Circula- tion. 2012;125:2353 62. 3.2.3. Timing of Intervention 1. Kapadia SR, Leon MB, Makkar RR, et al. 5-Year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385:2485 91. 2. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implanta- tion for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597 607. 3. Makkar RR, Fontana GP, Jilaihawi H, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012;366:1696 704. 4. Otto CM, Pearlman AS. Doppler echocardiography in adults with symp- tomatic aortic stenosis. Diagnostic utility and cost-effectiveness. Arch In- tern Med. 1988;148:2553 60. 5. Turina J, Hess O, Sepulcri F, et al. Spontaneous course of aortic valve dis- ease. Eur Heart J. 1987;8:471 83. 6. Kelly TA, Rothbart RM, Cooper CM, et al. 