2000;83:721 5. 8. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005 11. 9. Go AS, Mozaffarian D, Roger VL, et al. Executive summary: heart disease and stroke statistics 2013 update: a report from the American Heart As- sociation. Circulation. 2013;127:143 52. 10. Hagler MA, Hadley TM, Zhang H, et al. TGF- signalling and reactive oxy- gen species drive fibrosis and matrix remodelling in myxomatous mitral valves. Cardiovasc Res. 2013;99:175 84. 11. Miller JD, Weiss RM, Heistad DD. Calcific aortic valve stenosis: methods, models, and mechanisms. Circ Res. 2011;108:1392 412. 12. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-centered re- search in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. 16.2. Medical Therapy to Treat or Prevent Disease Progression: Stage B 1. Park SJ, Dweck MR. Multimodality imaging for the assessment of severe aortic stenosis. J Cardiovasc Imaging. 2019;27:235 46. 2. Everett RJ, Dweck MR. Renin-angiotensin system inhibition in aortic ste- nosis: thinking beyond transcatheter aortic valve replacement. J Am Coll Cardiol. 2019;74:642 4. 3. Lindman BR, Otto CM, Douglas PS, et al. Blood pressure and arterial load after transcatheter aortic valve replacement for aortic stenosis. Circ Car- diovasc Imaging. 2017;10:e006308. 4. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503 12. 5. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-cen- tered research in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. 16.3. Optimal Timing of Intervention: Stage C 1. Nicolau S, Ionescu T, Cleanoveanu G, et al. 