Abstract
The calcific aortic valve stenosis is one of the most common heart valve diseases in the western countries and its prevalence is growing with the aging of population. The second cause of aortic valve stenosis in the developed countries comes from rheumatic disease. The third cause of aortic valve stenosis in terms of prevalence comes from congenital anatomic variations, unicuspid or bicuspid valves. Several mechanisms are involved in the process of progressive calcification. Inflammation, risk factors for atherosclerosis, oxygen free radicals, and calcium metabolism alteration cause a progressive sclerosis and calcification of the valve leading to a leaflet movement reduction and pressure gradient increase across the valve. With progressive reduction of leaflets movement, there is a continuum spectrum of augmented pressure overload of the left ventricle with the consequent development of myocardial hypertrophy. The mechanisms of valve degeneration and ventricle response are elucidated in this chapter.
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References
Iung B. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on valvular heart disease. Eur Heart J [Internet]. 2003;24(13):1231–43. http://eurheartj.oxfordjournals.org/content/24/13/1231.long
Lindroos M, Kupari M, Heikkilä J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993;21(5):1220–5.
Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, et al. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol. 1997;29(3):630–4.
Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med [Internet]. 1999;341(3):142–7. http://www.nejm.org/doi/abs/10.1056/NEJM199907153410302
Cimini M, Boughner DR, Ronald JA, Aldington L, Rogers KA. Development of aortic valve sclerosis in a rabbit model of atherosclerosis: an immunohistochemical and histological study. J Heart Valve Dis. 2005;14(3):365–75.
Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O’Brien KD. Characterization of the early lesion of “degenerative” valvular aortic stenosis: histological and immunohistochemical studies. Circulation. 1994;90(2):844–53.
Wallby L, Janerot-Sjöberg B, Steffensen T, Broqvist M. T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves. Heart [Internet]. 2002;88(4):348–51. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1767380&tool=pmcentrez&rendertype=abstract
Olsson M, Rosenqvist M, Nilsson J. Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis. J Am Coll Cardiol. 1994;24(7):1664–71.
Kaden JJ, Dempfle CE, Grobholz R, Tran HT, Kilic R, Sarikoc A, et al. Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis [Internet]. 2003;170(2):205–11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14612199%5Cn http://www.sciencedirect.com/science/article/pii/S0021915003002843
Jian B, Narula N, Li QY, Mohler ER, Levy RJ. Progression of aortic valve stenosis: TGF-β1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75(2):457–65.
Helske S, Lindstedt KA, Laine M, Mäyränpää M, Werkkala K, Lommi J, et al. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol. 2004;44(9):1859–66.
Ghaisas NK, Foley JB, O’Briain DS, Crean P, Kelleher D, Walsh M. Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement. J Am Coll Cardiol [Internet]. 2000;36(7):2257–62. http://www.sciencedirect.com/science/article/pii/S0735109700009980
Weinberg EJ, Kaazempur Mofrad MR. A multiscale computational comparison of the bicuspid and tricuspid aortic valves in relation to calcific aortic stenosis. J Biomech. 2008;41(16):3482–7.
Robicsek F, Thubrikar MJ, Fokin AA. Cause of degenerative disease of the trileaflet aortic valve: review of subject and presentation of a new theory. Ann Thorac Surg. 2002;73:1346–54.
Stritzke J, Linsel-Nitschke P, Markus MRP, Mayer B, Lieb W, Luchner A, et al. Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey. Eur Heart J. 2009;30(16):2044–53.
Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol [Internet]. 1997;29(3):630–4. http://www.ncbi.nlm.nih.gov/pubmed/9060903.
Olsen MH, Wachtell K, Bella JN, Gerdts E, Palmieri V, Nieminen MS, et al. Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy). Am J Cardiol. 2005;95(1):132–6.
Miller JD, Chu Y, Brooks RM, Richenbacher WE, Peña-Silva R, Heistad DD. Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans. J Am Coll Cardiol. 2008;52(10):843–50.
Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437(7056):270–4.
Cosmi JE, Kort S, Tunick PA, Rosenzweig BP, Freedberg RS, Katz ES, et al. The risk of the development of aortic stenosis in patients with “benign” aortic valve thickening. Arch Intern Med [Internet]. 2002;162(20):2345. http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinte.162.20.2345
Mohler ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001;103(11):1522–8.
Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005;111:3316–26.
Clavel M-A, Pibarot P, Messika-Zeitoun D, Capoulade R, Malouf J, Aggarval S, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis results of an international registry study. J Am Coll Cardiol. 2014;64:1202–13.
Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56(1):56–64.
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med [Internet]. 1990;322(22):1561–6. http://www.ncbi.nlm.nih.gov/pubmed/2139921
Salcedo EE, Korzick DH, Currie PJ, Stewart WJ, Lever HM, Goormastic M. Determinants of left ventricular hypertrophy in patients with aortic stenosis. Cleve Clin J Med. 1989;56(6):590–6.
Kupari M, Turto H, Lommi J. Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure? Eur Heart J. 2005;26(17):1790–6.
Gunther S, Grossman W. Determinants of ventricular function in pressure-overload hypertrophy in man. Circulation. 1979;59(4):679–88.
Dweck MR, Joshi S, Murigu T, Gulati A, Alpendurada F, Jabbour A, et al. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson [Internet]. 2012;14(1):50. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3457907&tool=pmcentrez&rendertype=abstract
Orlowska-Baranowska E, Placha G, Gaciong Z, Baranowski R, Zakrzewski D, Michalek P, et al. Influence of ACE I/D genotypes on left ventricular hypertrophy in aortic stenosis: gender-related differences. J Heart Valve Dis [Internet]. 2004;13(4):574–81. http://www.ncbi.nlm.nih.gov/pubmed/15311863.
Rieck AE, Cramariuc D, Staal EM, Rossebø AB, Wachtell K, Gerdts E. Impact of hypertension on left ventricular structure in patients with asymptomatic aortic valve stenosis (a SEAS substudy). J Hypertens. 2010;28(2):377–83.
Briand M, Dumesnil JG, Kadem L, Tongue AG, Rieu R, Garcia D, et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment. J Am Coll Cardiol. 2005;46(2):291–8.
Hachicha Z, Dumesnil JG, Pibarot P. Usefulness of the valvuloarterial impedance to predict adverse outcome in asymptomatic aortic stenosis. J Am Coll Cardiol. 2009;54(11):1003–11.
Cioffi G, Faggiano P, Vizzardi E, Tarantini L, Cramariuc D, Gerdts E, et al. Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart. 2011;97(4):301–7.
Bishopric NH, Andreka P, Slepak T, Webster KA. Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 2001;1(2):141–50.
Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, et al. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995;96(5):2247–59.
Pierzchalski P, Reiss K, Cheng W, Cirielli C, Kajstura J, Nitahara JA, et al. p53 induces myocyte apoptosis via the activation of the renin-angiotensin system. Exp Cell Res. 1997;234(1):57–65.
Camici PG, Olivotto I, Rimoldi OE. The coronary circulation and blood flow in left ventricular hypertrophy. J Mol Cell Cardiol. 2012;52:857–64.
Anderson KR, Sutton MGSJ, Lie JT. Histopathological types of cardiac fibrosis in myocardial disease. J Pathol. 1979;128(2):79–85.
Krayenbuehl HP, Hess OM, Monrad ES, Schneider J, Mall G, Turina M. Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement. Circulation. 1989;79(4):744–55.
Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Investig. 2007;117:568–75.
Bishop JE, Lindahl G. Regulation of cardiovascular collagen synthesis by mechanical load. Cardiovasc Res. 1999;42(1):27–44.
Treibel TA, López B, González A, Menacho K, Schofield RS, Ravassa S, et al. Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients. Eur Heart J [Internet]. 2017. https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehx353
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Di Giammarco, G., Marinelli, D. (2019). Pathophysiology of Aortic Valve Stenosis. In: Giordano, A., Biondi-Zoccai, G., Frati, G. (eds) Transcatheter Aortic Valve Implantation. Springer, Cham. https://doi.org/10.1007/978-3-030-05912-5_3
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DOI: https://doi.org/10.1007/978-3-030-05912-5_3
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