Pathology of calcific aortic stenosis

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Vaishnava P, Fuster V, Goldman M, Bonow RO. Surgery for asymptomatic degenerative aortic and mitral valve disease. Nat. Rev. Cardiol.8(3),173–177 (2011).
  MedlineGoogle Scholar
• 2  Roberts WC. The structure of the aortic valve in clinically isolated aortic stenosis. An autopsy study of 162 patients over 15 years of age. Circulation42(1),91–97 (1970).
  Medline CASGoogle Scholar
• 3  Subramanian R, Olson LJ, Edwards WD. Surgical pathology of pure aortic stenosis. A study of 374 cases. Mayo Clin. Proc.59(10),683–690 (1984).
  Medline CASGoogle Scholar
• 4  Passik CS, Ackermann DM, Pluth JR, Edwards WD. Temporal changes in the causes of aortic stenosis. A surgical pathologic study of 646 cases. Mayo Clin. Proc.62(2),119–123 (1987).
  Medline CASGoogle Scholar
• 5  Collins MJ, Butany J, Borger MA, Strauss BH, David TE. Implications of a congenitally abnormal valve. A study of 1025 consecutively excised aortic valves. J. Clin. Pathol.61(4),530–536 (2008).▪ Important pathology study evaluating over 1000 surgically removed aortic valves highlighting salient morphologic differences.
  Medline CASGoogle Scholar
• 6  Baumgartner H, Hung J, Bermejo J et al. Echocardiographic assessment of valve stenosis. EAE/ASE recommendations for clinical practice. J. Am. Soc. Echocardiogr.22(1),1–23; quiz 101–102 (2009).
  MedlineGoogle Scholar
• 7  Baumgartner H, Hung J, Bermejo J et al. Echocardiographic assessment of valve stenosis. EAE/ASE recommendations for clinical practice. Eur. J. Echocardiogr.10(1),1–25 (2009).
  MedlineGoogle Scholar
• 8  Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH. Progression of valvular aortic stenosis in adults: literature review and clinical implications. Am. Heart J.132(2 Pt 1),408–417 (1996).
  Medline CASGoogle Scholar
• 9  Cosmi JE, Kort S, Tunick PA et al. The risk of the development of aortic stenosis in patients with “benign” aortic valve thickening. Arch. Intern. Med.162(20),2345–2347 (2002).
  MedlineGoogle Scholar
• 10  Davies SW, Gershlick AH, Balcon R. Progression of valvar aortic stenosis: a long-term retrospective study. Eur. Heart J.12(1),10–14 (1991).
  Medline CASGoogle Scholar
• 11  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.341(3),142–147 (1999).▪▪ Landmark study demonstrating association of aortic sclerosis with cardiovascular morbidity and mortality including myocardial infarction.
  Medline CASGoogle Scholar
• 12  Boon A, Cheriex E, Lodder J, Kessels F. Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve. Heart78(5),472–474 (1997).
  Medline CASGoogle Scholar
• 13  Yip CY, Simmons CA. The aortic valve microenvironment and its role in calcific aortic valve disease. Cardiovasc. Pathol.20(3),177–182 (2011).
  MedlineGoogle Scholar
• 14  Simmons CA, Grant GR, Manduchi E, Davies PF. Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in normal porcine aortic valves. Circ. Res.96(7),792–799 (2005).
  Medline CASGoogle Scholar
• 15  Butany J, Collins MJ, Demellawy DE et al. Morphological and clinical findings in 247 surgically excised native aortic valves. Can. J. Cardiol.21(9),747–755 (2005).
  MedlineGoogle Scholar
• 16  Roberts WC, Ko JM. Weights of individual cusps in operatively-excised stenotic three-cuspid aortic valves. Am. J. Cardiol.94(5),681–684 (2004).
  MedlineGoogle Scholar
• 17  Kahlert P, Knipp SC, Schlamann M et al. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation121(7),870–878 (2010).
  MedlineGoogle Scholar
• 18  Roberts WC. Morphologic aspects of cardiac valve dysfunction. Am. Heart J.123(6),1610–1632 (1992).
  Medline CASGoogle Scholar
• 19  Sabet HY, Edwards WD, Tazelaar HD, Daly RC. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases. Mayo Clin. Proc.74(1),14–26 (1999).
  Medline CASGoogle Scholar
• 20  Larson EW, Edwards WD. Risk factors for aortic dissection: a necropsy study of 161 cases. Am. J. Cardiol.53(6),849–855 (1984).
  Medline CASGoogle Scholar
• 21  Gore I, Seiwert VJ. Dissecting aneurysm of the aorta; pathological aspects; an analysis of eighty-five fatal cases. AMA Arch. Pathol.53(2),121–141 (1952).
  Medline CASGoogle Scholar
• 22  Roberts CS, Roberts WC. Dissection of the aorta associated with congenital malformation of the aortic valve. J. Am. Coll. Cardiol.17(3),712–716 (1991).
  Medline CASGoogle Scholar
• 23  Fedak PW, de Sa MP, Verma S et al. Vascular matrix remodeling in patients with bicuspid aortic valve malformations: implications for aortic dilatation. J. Thorac. Cardiovasc. Surg.126(3),797–806 (2003).
  MedlineGoogle Scholar
• 24  Isner JM, Chokshi SK, DeFranco A, Braimen J, Slovenkai GA. Contrasting histoarchitecture of calcified leaflets from stenotic bicuspid versus stenotic tricuspid aortic valves. J. Am. Coll. Cardiol.15(5),1104–1108 (1990).
  Medline CASGoogle Scholar
• 25  Stewart BF, Siscovick D, Lind BK et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J. Am. Coll. Cardiol.29(3),630–634 (1997).
  Medline CASGoogle Scholar
• 26  Gotoh T, Kuroda T, Yamasawa M et al. Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study). Am. J. Cardiol.76(12),928–932 (1995).
  Medline CASGoogle Scholar
• 27  Wilmshurst PT, Stevenson RN, Griffiths H, Lord JR. A case-control investigation of the relation between hyperlipidaemia and calcific aortic valve stenosis. Heart78(5),475–479 (1997).
  Medline CASGoogle Scholar
• 28  Thanassoulis G, Massaro JM, Cury R et al. Associations of long-term and early adult atherosclerosis risk factors with aortic and mitral valve calcium. J. Am. Coll. Cardiol.55(22),2491–2498 (2010).
  Medline CASGoogle Scholar
• 29  Briand M, Lemieux I, Dumesnil JG et al. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. J. Am. Coll. Cardiol.47(11),2229–2236 (2006).
  MedlineGoogle Scholar
• 30  Pohle K, Maffert R, Ropers D et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation104(16),1927–1932 (2001).
  Medline CASGoogle Scholar
• 31  Shavelle DM, Takasu J, Budoff MJ, Mao S, Zhao XQ, O’Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet359(9312),1125–1126 (2002).
  Medline CASGoogle Scholar
• 32  Moura LM, Ramos SF, Zamorano JL et al. Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis. J. Am. Coll. Cardiol.49(5),554–561 (2007).
  Medline CASGoogle Scholar
• 33  Cowell SJ, Newby DE, Prescott RJ et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N. Engl. J. Med.352(23),2389–2397 (2005).
  Medline CASGoogle Scholar
• 34  Rossebo AB, Pedersen TR, Boman K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N. Engl. J. Med.359(13),1343–1356 (2008).
  MedlineGoogle Scholar
• 35  Chan KL, Teo K, Dumesnil JG, Ni A, Tam J. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation121(2),306–314 (2010).▪▪ Results of the ASTRONOMER trial demonstrating that cholesterol lowering with rosuvastatin does not reduce progression of calcific aortic stenosis.
  Medline CASGoogle Scholar
• 36  Ngo DT, Sverdlov AL, Willoughby SR et al. Determinants of occurrence of aortic sclerosis in an aging population. JACC Cardiovasc. Imaging2(8),919–927 (2009).
  MedlineGoogle Scholar
• 37  Sarphie TG. Interactions of IgG and β-VLDL with aortic valve endothelium from hypercholesterolemic rabbits. Atherosclerosis68(3),199–212 (1987).
  Medline CASGoogle Scholar
• 38  Sarphie TG. A cytochemical study of the surface properties of aortic and mitral valve endothelium from hypercholesterolemic rabbits. Exp. Mol. Pathol.44(3),281–296 (1986).
  Medline CASGoogle Scholar
• 39  Sarphie TG. Surface responses of aortic valve endothelia from diet-induced, hypercholesterolemic rabbits. Atherosclerosis54(3),283–299 (1985).
  Medline CASGoogle Scholar
• 40  Rajamannan NM, Sangiorgi G, Springett M et al. Experimental hypercholesterolemia induces apoptosis in the aortic valve. J. Heart. Valve Dis.10(3),371–374 (2001).▪ Seminal research study demonstrating experimental hypercholesterolemia as cause of atherosclerosis and calcification in rabbit aortic valves with disease inhibition by atorvastatin.
  Medline CASGoogle Scholar
• 41  Rajamannan NM, Subramaniam M, Springett M et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation105(22),2660–2665 (2002).▪ Seminal research study demonstrating experimental hypercholesterolemia cause of atherosclerosis and calcification in rabbit aortic valves with disease inhibition by atorvastatin.
  Medline CASGoogle Scholar
• 42  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.14(3),365–375 (2005).
  MedlineGoogle Scholar
• 43  Drolet MC, Arsenault M, Couet J. Experimental aortic valve stenosis in rabbits. J. Am. Coll. Cardiol.41(7),1211–1217 (2003).
  MedlineGoogle Scholar
• 44  Rajamannan NM, Subramaniam M, Caira F, Stock SR, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway. Circulation112(9 Suppl.),I229–I234 (2005).
  MedlineGoogle Scholar
• 45  Rajamannan NM. Calcific aortic stenosis: lessons learned from experimental and clinical studies. Arterioscler. Thromb. Vasc. Biol.29(2),162–168 (2009).
  Medline CASGoogle Scholar
• 46  Hjortnaes J, Butcher J, Figueiredo JL et al. Arterial and aortic valve calcification inversely correlates with osteoporotic bone remodelling: a role for inflammation. Eur. Heart J.31(16),1975–1984 (2010).
  Medline CASGoogle Scholar
• 47  Browner WS, Seeley DG, Vogt TM, Cummings SR. Non-trauma mortality in elderly women with low bone mineral density. Study of Osteoporotic Fractures Research Group. Lancet338(8763),355–358 (1991).
  Medline CASGoogle Scholar
• 48  Uyama O, Yoshimoto Y, Yamamoto Y, KawaiA. Bone changes and carotid atherosclerosis in postmenopausal women. Stroke28(9),1730–1732 (1997).
  Medline CASGoogle Scholar
• 49  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. Circulation90(2),844–853 (1994).▪▪ Early pathology study demonstrating histologic and immunohistochemical features of early calcific aortic stenosis lesions.
  Medline CASGoogle Scholar
• 50  Mazzone A, Epistolato MC, De Caterina R et al. Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis. J. Am. Coll. Cardiol.43(9),1670–1676 (2004).
  Medline CASGoogle Scholar
• 51  Soini Y, Salo T, Satta J. Angiogenesis is involved in the pathogenesis of nonrheumatic aortic valve stenosis. Hum. Pathol.34(8),756–763 (2003).
  Medline CASGoogle Scholar
• 52  Vollebergh FE, Becker AE. Minor congenital variations of cusp size in tricuspid aortic valves. Possible link with isolated aortic stenosis. Br. Heart J.39(9),1006–1011 (1977).
  Medline CASGoogle Scholar
• 53  Mirzaie M, Meyer T, Schorn B et al. Calcification tendency of various biological aortic valves in an experimental animal model. Cardiovasc. Surg.7(7),735–741 (1999).
  Medline CASGoogle Scholar
• 54  Bailey MT, Pillarisetti S, Xiao H, Vyavahare NR. Role of elastin in pathologic calcification of xenograft heart valves. J. Biomed. Mater. Res. A.66(1),93–102 (2003).
  MedlineGoogle Scholar
• 55  Dunmore-Buyze J, Boughner DR, Macris N, Vesely I. A comparison of macroscopic lipid content within porcine pulmonary and aortic valves. Implications for bioprosthetic valves. J. Thorac. Cardiovasc. Surg.110(6),1756–1761 (1995).
  Medline CASGoogle Scholar
• 56  Proudfoot D, Shanahan CM. Biology of calcification in vascular cells: intima versus media. Herz26(4),245–251 (2001).
  Medline CASGoogle Scholar
• 57  Fitzpatrick LA, Severson A, Edwards WD, Ingram RT. Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis. J. Clin. Invest.94(4),1597–1604 (1994).
  Medline CASGoogle Scholar
• 58  Kwon HM, Hong BK, Kang TS et al. Expression of osteopontin in calcified coronary atherosclerotic plaques. J. Korean Med. Sci.15(5),485–493 (2000).
  Medline CASGoogle Scholar
• 59  O’Brien ER, Garvin MR, Stewart DK et al. Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. Arterioscler. Thromb.14(10),1648–1656 (1994).
  MedlineGoogle Scholar
• 60  O’Brien KD, Kuusisto J, Reichenbach DD et al. Osteopontin is expressed in human aortic valvular lesions. Circulation92(8),2163–2168 (1995).
  MedlineGoogle Scholar
• 61  Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation103(11),1522–1528 (2001).
  MedlineGoogle Scholar
• 62  Rajamannan NM, Subramaniam M, Rickard D et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation107(17),2181–2184 (2003).▪ Study demonstrating that osteoblast phenotypes are present in calcifying valve tissue and may be involved in regulation of tissue calcium.
  MedlineGoogle Scholar
• 63  Mazzone A, Epistolato MC, Gianetti J et al. Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis: two different sites of the same disease? Am. J. Clin. Pathol.126(4),494–502 (2006).
  MedlineGoogle Scholar
• 64  Avakian SD, Annicchino-Bizzacchi JM, Grinberg M, Ramires JA, Mansura AP. Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis. Clin. Genet.60(5),381–384 (2001).
  Medline CASGoogle Scholar
• 65  Novaro GM, Sachar R, Pearce GL, Sprecher DL, Griffin BP. Association between apolipoprotein E alleles and calcific valvular heart disease. Circulation108(15),1804–1808 (2003).
  Medline CASGoogle Scholar
• 66  Ortlepp JR, Hoffmann R, Ohme F, Lauscher J, Bleckmann F, Hanrath P. The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart85(6),635–638 (2001).
  Medline CASGoogle Scholar
• 67  Garg V, Muth AN, Ransom JF et al. Mutations in NOTCH1 cause aortic valve disease. Nature437(7056),270–274 (2005).
  Medline CASGoogle Scholar
• 68  Probst V, Le Scouarnec S, Legendre A et al. Familial aggregation of calcific aortic valve stenosis in the western part of France. Circulation113(6),856–860 (2006).
  MedlineGoogle Scholar
• 69  Hammermeister KE, Sethi GK, Henderson WG, Oprian C, Kim T, Rahimtoola S. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans Affairs Cooperative Study on Valvular Heart Disease. N. Engl. J. Med.328(18),1289–1296 (1993).
  Medline CASGoogle Scholar
• 70  Butany J, Yu W, Silver MD, David TE. Morphologic findings in explanted Hancock II porcine bioprostheses. J. Heart Valve Dis.8(1),4–15 (1999).
  Medline CASGoogle Scholar
• 71  Kopf GS, Geha AS, Hellenbrand WE, Kleinman CS. Fate of left-sided cardiac bioprosthesis valves in children. Arch. Surg.121(4),488–490 (1986).
  Medline CASGoogle Scholar
• 72  Fishbein MC, Levy RJ, Ferrans VJ et al. Calcifications of cardiac valve bioprostheses. Biochemical, histologic, and ultrastructural observations in a subcutaneous implantation model system. J. Thorac. Cardiovasc. Surg.83(4),602–609 (1982).▪ Important pathology study from expert cardiovascular pathologists evaluating mechanisms of calcification in bioprosthetic heart valves. Studies include animal models and explanted valves.
  Medline CASGoogle Scholar
• 73  Schoen FJ, Levy RJ. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann. Thorac. Surg.79(3),1072–1080 (2005).▪ Important pathology study from expert cardiovascular pathologists evaluating mechanisms of calcification in bioprosthetic heart valves. Studies include animal models and explanted valves.
  MedlineGoogle Scholar
• 74  Tomazic BB, Edwards WD, Schoen FJ. Physicochemical characterization of natural and bioprosthetic heart valve calcific deposits: implications for prevention. Ann. Thorac. Surg.60(Suppl. 2),S322–S327 (1995).
  Medline CASGoogle Scholar
• 75  Schoen FJ, Levy RJ. Tissue heart valves: current challenges and future research perspectives. Founder’s Award, 25th Annual Meeting of the Society for Biomaterials, perspectives. Providence, RI, USA, 28 April–2 May 1999. J. Biomed. Mater. Res.47(4),439–465 (1999).
  Medline CASGoogle Scholar
• 76  Levy RJ, Schoen FJ, Levy JT, Nelson AC, Howard SL, Oshry LJ. Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats. Am. J. Pathol.113(2),143–155 (1983).▪ Important pathology study from expert cardiovascular pathologists evaluating mechanisms of calcification in bioprosthetic heart valves. Studies include animal models and explanted valves.
  Medline CASGoogle Scholar
• 77  Schoen FJ, Levy RJ, Nelson AC, Bernhard WF, Nashef A, Hawley M. Onset and progression of experimental bioprosthetic heart valve calcification. Lab. Invest.52(5),523–532 (1985).
  Medline CASGoogle Scholar
• 78  Salgueira M, Jarava C, Alba R et al. Valvular heart calcifications in hemodialysis patients: an analysis of predisposing factors. Nefrologia18(3),221–226 (1998).
  Google Scholar
• 79  Briand M, Pibarot P, Despres JP et al. Metabolic syndrome is associated with faster degeneration of bioprosthetic valves. Circulation114(Suppl. 1),I512–I517 (2006).
  MedlineGoogle Scholar
• 80  Thubrikar MJ, Deck JD, Aouad J, Nolan SP. Role of mechanical stress in calcification of aortic bioprosthetic valves. J. Thorac. Cardiovasc. Surg.86(1),115–125 (1983).
  Medline CASGoogle Scholar
• 81  Owens DS, Otto CM. Is it time for a new paradigm in calcific aortic valve disease? JACC Cardiovasc. Imaging2(8),928–930 (2009).
  MedlineGoogle Scholar
• 82  Farb A, Virmani R, Burk AP. Pathology of valvular heart disease. In: Valvular Heart Disease. Alpert JS, Dalen JF, Rahimtoola SH (Eds). Lippincott, Williams & Wilkins, Philadelphia, PA, USA, 16 (2000).
  Google Scholar