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Morphology, Clinicopathologic Correlations, and Mechanisms in Heart Valve Health and Disease

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Abstract

The clinical and pathological features of the most frequent intrinsic structural diseases that affect the heart valves are well established, but heart valve disease mechanisms are poorly understood, and effective treatment options are evolving. Major advances in the understanding of the structure, function and biology of native valves and the pathobiology, biomaterials and biomedical engineering, and the clinical management of valvular heart disease have occurred over the past several decades. This communication reviews contemporary considerations relative to the pathology of valvular heart disease, including (1) clinical significance and epidemiology of valvular heart disease; (2) functional and dynamic valvular macro-, micro- and ultrastructure; (3) causes, morphology and mechanisms of human valvular heart disease; and (4) pathologic considerations in valve replacement, repair and, potentially, regeneration of the heart valves.

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References

  1. Adams, D. H., J. J. Popma, M. J. Reardon, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N. Engl. J. Med. 370:1790–1798, 2014.

    Article  Google Scholar 

  2. Aggarwal, A., A. M. Pouch, E. Lai, J. Lesicko, P. A. Yushkevich, J. H. Gorman, 3rd, et al. In-vivo heterogeneous functional and residual strains in human aortic valve leaflets. J. Biomech. 2016. doi:10.1016/j.jbiomech.2016.04.038.

    Google Scholar 

  3. Aikawa, E., and F. J. Schoen. Calcific and degenerative heart valve disease. In: Cellular and Molecular Basis of Cardiovascular Disease, edited by M. S. Willis, J. W. Homeister, and J. R. Stone. 2014, pp. 161–180.

    Chapter  Google Scholar 

  4. Aikawa, E., P. Whittaker, M. Farber, K. Mendelson, R. F. Padera, M. Aikawa, and F. J. Schoen. Human semilumar cardiac valve remodeling by activated cells from fetus to adult. Circulation 113:1344–1352, 2006.

    Article  Google Scholar 

  5. Alavi, S. H., and A. Kheradvar. A hybrid tissue-engineered heart valve. Ann. Thorac. Surg. 99:2183–2187, 2015.

    Article  Google Scholar 

  6. Armstrong, E. J., and J. Bischoff. Heart valve development. Epithelial cell signaling and differentiation. Circ. Res. 95:459–470, 2004.

    Article  Google Scholar 

  7. Arsalan, M., and T. Walther. Durability of prostheses for transcatheter aortic valve implantation. Nat. Rev. Cardiol. 13:360–367, 2016.

    Article  Google Scholar 

  8. Ayoub, S., Ferrari, G., Gorman, R. C., Gorman, J. H. 3rd, Schoen, F. J., Sacks, M. S. Heart valve biomechanics and underlying mechanobiology. Compr. Physiol. 2016 (in press)

  9. Bechtel, J. F., C. Muller-Steinhardtke, A. Brunswik, U. Stierle, and H. H. Sievers. Evaluation of the decellularized pulmonary valve homograft (SynerGraft). J. Heart Valve Dis. 12:734–739, 2003.

    Google Scholar 

  10. Bischoff, J., and E. Aikawa. Progenitor cells confer plasticity to cardiac valve endothelium. J Cardiovasc. Transl. Res. 4:710–719, 2011.

    Article  Google Scholar 

  11. Bonow, R. O., M. B. Leon, D. Dashi, and N. Moat. Management strategies and future challenges for aortic valve disease. Lancet 387:1312–1323, 2016.

    Article  Google Scholar 

  12. Boodhwani, M., and G. El Khoury. Aortic valve repair: indications and outcomes. Curr. Cardiol. Rep. 16:490, 2014. doi:10.1007/s11886-014-0490.7.

    Article  Google Scholar 

  13. Bourantas, C. V., and P. W. Serruys. Evolution of transcatheter aortic valve replacement. Circ. Res. 114:1037–1051, 2014.

    Article  Google Scholar 

  14. Bouten, C. V., A. Driessen-Mol, and F. P. Baaijens. In situ heart valve tissue engineering: simple devices, smart materials, complex knowledge. Expert Rev. Med. Devices 9:453–455, 2012.

    Article  Google Scholar 

  15. Brown, J. M., S. M. O’Brien, C. Wu, J. A. Sikora, B. P. Griffith, and J. S. Gammie. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J. Thorac. Cardiovasc. Surg. 137:82–90, 2009.

    Article  Google Scholar 

  16. Cahill, T. J., and B. D. Prendergast. Infective endocarditis. Lancet 387:882–893, 2016.

    Article  Google Scholar 

  17. Carabello, B. A. Aortic stenosis. New Engl J Med 346:677–682, 2002.

    Article  Google Scholar 

  18. Chakraborty, S., J. Cheek, B. Sakthivel, B. J. Aronow, and K. E. Yutzey. Shared gene expression profiles in developing heart valves and osteoblast progenitor cells. Physiol Genom 35:75–85, 2008.

    Article  Google Scholar 

  19. Cheatham, J. P., W. E. Hellenbrand, E. M. Zahn, T. K. Jones, D. P. Berman, J. A. Vincent, et al. Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replaement in the US Melody valve investigational device exemption trial. Circulation 131:1960–1970, 2015.

    Article  Google Scholar 

  20. Chester, A. H., I. El-Hamamsy, J. T. Butcher, N. Latif, S. Bertazzo, and M. H. Yacoub. The living aortic valve: from molecules to function. Glob. Cardiol. Sci. Practice 11:52–77, 2014.

    Google Scholar 

  21. Cheung, D. Y., B. Duan, and J. T. Butcher. Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions. Expert Opin. Biol. Ther. 15:1155–1172, 2015.

    Article  Google Scholar 

  22. Christie, G. W., and B. G. Barratt-Boyes. Age-dependent changes in the radial stretch of human aortic valve leaflets determined by biaxial testing. Ann. Thorac. Surg. 60:S156–S158, 1995.

    Article  Google Scholar 

  23. Di Bardino, D., A. El Bardissi, S. McClure, et al. Four decades experience with mitral valve repair: analysis of differential indications, technical evolution, and long term outcome. J. Thorac. Cardiovasc. Surg. 139:76–84, 2010.

    Article  Google Scholar 

  24. Dreger, S. A., P. M. Taylor, S. P. Allen, and M. H. Yacoub. Profile and localization of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in human heart valves. J. Heart Valve Dis. 11:875–880, 2002.

    Google Scholar 

  25. Dvir, D., M. Barbanti, J. Tan, and J. G. Webb. Transcatheter aortic valve-in-valve implantation for patients with degenerative surgical bioprosthetic valves. Curr. Probl. Cardiol. 39:7–27, 2014.

    Article  Google Scholar 

  26. Dweck, M. R., H. J. Khaw, G. K. Z. Sng, E. L. Luo, A. Baird, M. C. Williams, et al. Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur. Heart J. 34:1567–1574, 2013.

    Article  Google Scholar 

  27. Fassa, A. A., D. Himbert, and A. Vahanian. Mechanisms and management of TAVR-related complications. Nat. Rev. Cardiol. 10:685–696, 2013.

    Article  Google Scholar 

  28. Flameng, W., F. Rega, M. Vercalsteren, P. Herijgers, and B. Meuris. Antimineralization treatment and patient-prosthesis mismatch are major determinants of the onset and incidence of structural valve degeneration in bioprosthetic heart valves. J. Thorac. Cardiovasc. Surg. 147:1219–1224, 2014.

    Article  Google Scholar 

  29. Gammie, J. S., S. Sheng, B. P. Griffith, et al. Trends in mitral valve surgery in the United States: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann. Thorac. Surg. 87:1431–1439, 2009.

    Article  Google Scholar 

  30. Ghazanfari, S., A. Driessen-Mol, B. Sanders, P. E. Dijkman, S. P. Hoerstrup, F. P. Baaijens, et al. In vivo collagen remodeling in the vascular wall of decellularized stented tissue-engineered heart valves. Tissue Eng. A 21:2206–2215, 2015.

    Article  Google Scholar 

  31. Goettsch, C., J. D. Hutcheson, and E. Aikawa. MicroRNA in cardiovascular calcification. Focus on targets and extracellular vesicle delivery mechanism. Circ. Res. 112:1073–1084, 2013.

    Article  Google Scholar 

  32. Hamm, C. V. V., M. Arsalan, and M. J. Mack. The future of transcatheter aortic valve implantation. Eur. Heart J. 37:803–810, 2016.

    Article  Google Scholar 

  33. Hilbert, S. L., F. J. Schoen, and V. J. Ferrans. Allograft heart valves: Morphologic, biomechanical and explant pathology studies. In: Cardiac Reconstructions with Allograft Tissues2nd, edited by R. Hopkins. New York: Springer, 2004, pp. 193–233.

    Google Scholar 

  34. Hinton, R. B., and K. E. Yutzey. Heart valve structure and function in development and disease. Ann. Rev. Physiol. 73:29–46, 2011.

    Article  Google Scholar 

  35. Hoerstrup, S. P., R. Sodian, S. Daebritz, J. Wang, E. A. Bacha, D. P. Martin, et al. Functional living trileaflet heart valves grown in-vitro. Circulation 102:III-44–III-49, 2000.

    Article  Google Scholar 

  36. Honda, S., T. Miyamoto, T. Watanabe, T. Narumi, S. Kadowaki, Y. Honda, et al. A novel mouse model of aortic valve stenosis induced by direct wire injury. Arterioscler. Thromb. Vasc. Biol. 34:270–278, 2014.

    Article  Google Scholar 

  37. Huang, G., and S. H. Rahimtoola. Prosthetic heart valve. Circulation 123:2602–2605, 2011.

    Article  Google Scholar 

  38. Iung, B., and A. Vahanian. Epidemiology of acquired valvular heart disease. Can. J. Cardiol. 30:962–970, 2014.

    Article  Google Scholar 

  39. Jung, J. J., M. Razavian, A. A. Challa, L. Nie, R. Golestani, J. Zhang, et al. Multimodality and molecular imaging of matrix metalloproteinase activation in calcific aortic valve disease. J. Nucl. Med. 56:933–938, 2015.

    Article  Google Scholar 

  40. Kapadia, S. R., M. B. Leon, R. R. Makkar, E. M. Tuzcu, L. G. Svensson, S. Kodali, et al. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperative aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 385:2485–2491, 2015.

    Article  Google Scholar 

  41. Kheradvar, A., E. M. Groves, L. P. Dasi, S. H. Alavi, R. Tranquillo, K. J. Grande-Allen, et al. Emerging trends in heart valve engineering: Part 1. Solutions for future. Ann. Biomed. Eng. 43:833–843, 2015.

    Article  Google Scholar 

  42. Kheradvar, A., E. M. Groves, C. J. Goergen, S. H. Alavi, R. Tranquillo, C. A. Simmons, et al. Emerging trends in heart valve engineering: Part 2. Novel and standard technologies for aortic valve replacement. Ann. Biomed. Eng. 43:844–857, 2015.

    Article  Google Scholar 

  43. Kheradvar, A., E. M. Groves, C. A. Simmons, B. Griffith, S. H. Alavi, R. Tranquillo, et al. Emerging Trends in heart valve engineering: Part 3. Novel technologies for mitral valve repair and replacement. Ann. Biomed. Eng. 43:858–870, 2015.

    Article  Google Scholar 

  44. Kurobe, H., M. W. Maxfield, C. K. Breuer, and T. Shinoka. Concise review: tissue-engineered vascular grafts for cardiac surgery: past, present, and future. Stem Cell Transl. Med. 1:5665–5671, 2012.

    Google Scholar 

  45. Latif, N., A. Quillon, P. Sarathchandra, A. McCormack, A. Lozanoski, M. H. Yacoub, et al. Modulation of human valve interstitial cell phenotype and function using a fibroblast growth factor 2 formulation. PLoS ONE 10:e0127844, 2015.

    Article  Google Scholar 

  46. Law, K. B., K. R. Phillips, and J. Butany. Pulmonary valve-in-valve implants: how long do they prolong reintervention and what causes them to fail? Cardiovasc. Pathol. 21:519–521, 2012.

    Article  Google Scholar 

  47. Levine, R. A., A. A. Hagege, D. P. Judge, M. Padala, J. P. Dal-Bianco, E. Aikawa, et al. Mitral valve disease—morphology and mechanism. Nat. Rev. Cardiol. 12:689–710, 2015.

    Article  Google Scholar 

  48. Levy, R. J., F. J. Schoen, and S. Howard. Mechanism of calcification of porcine aortic valve cusps: role of T-lymphocytes. Am. J. Cardiol. 52:629–631, 1983.

    Article  Google Scholar 

  49. Li, C., S. Xu, and A. I. Gotlieb. The response to valve injury. A paradigm to understand the pathogenesis of heart valve disease. Cardiovasc. Pathol. 20:183–190, 2011.

    Article  Google Scholar 

  50. Li, C., S. Xu, and A. I. Gotlieb. The progression of calcific aortic valve disease through injury, cell dysfunction, and disruptive biologic and physical force feedback loops. Cardiovasc. Pathol. 22:1–8, 2013.

    Article  Google Scholar 

  51. Lincoln, J., and V. Garg. Etiology of valvular heart disease. Genetic and developmental origins. Circ. J. 78:1801–1807, 2014.

    Article  Google Scholar 

  52. Liu, A. C., V. R. Joag, and A. I. Gotlieb. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am. J. Pathol. 171:1407–1418, 2007.

    Article  Google Scholar 

  53. Lueders, C., B. Jastram, R. Hetzer, and H. Schwandt. Rapid manufacturing techniques for the tissue engineering of human heart valves. Eur. J. Cardiothorac. Surg. 46:593–601, 2014.

    Article  Google Scholar 

  54. MacGrogan, D., G. Luxan, A. Driessen-Mol, C. Bouten, F. Baaijens, and J. L. de la Pompa. How to make a heart valve: from embryonic development to bioengineering of living valve substitutes. Cold Spring Harb Perspect Med. 4:a013912, 2014.

    Article  Google Scholar 

  55. Mack, M. J., M. B. Leon, C. R. Smith, D. C. Miller, J. W. Moses, E. M. Tuzcu, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 385:2477–2484, 2015.

    Article  Google Scholar 

  56. Makkar, R. R., G. Fontana, H. Jilaihawi, T. Chakravarty, K. F. Kofoed, O. de Backer, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N. Engl. J. Med. 373:2015–2024, 2015.

    Article  Google Scholar 

  57. Manji, R. Z., B. Skser, A. H. Henkis, and D. K. C. Cooper. Bioprosthetic heart valves of the future. Xenotransplantation 21:1–10, 2014.

    Article  Google Scholar 

  58. Markwald, R. R., R. A. Norris, R. Moreno-Rodriguez, and R. A. Levine. Developmental basis of adult cardiovascular diseases: valvular heart diseases. Ann. N.Y. Acad Sci. 2007(1188):177–183, 2010.

    Article  Google Scholar 

  59. Masoumi, N., N. Annabi, A. Assmann, B. L. Larson, J. Hjortnaes, N. Alemdar, et al. Tri-layered elastomeric scaffolds for engineering heart valve leaflets. Biomaterials 35:7774–7785, 2014.

    Article  Google Scholar 

  60. Matheny, R. G., M. L. Hutchison, P. E. Dryden, H. D. Hiles, and C. J. Shaar. Porcine small intestine submucosa as a pulmonary valve leaflet substitute. J. Heart Valve Dis. 9:769–774, 2000.

    Google Scholar 

  61. Mendelson, K. M., and F. J. Schoen. Heart valve tissue engineering: concepts, approaches, progress, and challenges. Ann. Biomed Eng. 34:1799–1819, 2006.

    Article  Google Scholar 

  62. Mitchell, R. N., R. A. Jonas, and F. J. Schoen. Pathology of explanted cryopreserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J. Thorac. Cardiovasc. Surg. 115:118–127, 1998.

    Article  Google Scholar 

  63. Mohr, F. W. Decade in review—valvular disease: Current perspectives on treatment of valvular heart disease. Nat. Rev. Cardiol. 11:637–638, 2014.

    Article  Google Scholar 

  64. Mongkoldhumrongkul, N., M. H. Yacoub, and A. H. Chester. Valve endothelial cells—not just any old endothelial cells. Curr. Vasc. Pharmacol. 14:146–154, 2016.

    Article  Google Scholar 

  65. Mordi, I., and N. Tzemos. Bicuspid aortic valve disease: a comprehensive review. Cardiol. Res. Pract. 2012. doi:10.1155/2012/196037.

    Google Scholar 

  66. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation 2016;133:e38–e60.

    Article  Google Scholar 

  67. Mylotte, D., A. Andalib, P. Theriault-Lauzier, M. Dorfmeister, M. Girgis, W. Alharnbi, et al. Transcatheter heart valve failure: a systematic review. Eur. Heart J. 36:1306–1327, 2015.

    Article  Google Scholar 

  68. Nishimura, R. A., C. M. Otto, R. O. Bonow, B. A. Carabello, J. P. Erwin 3rd, R. A. Guyton, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 63:e57–e185, 2014.

    Article  Google Scholar 

  69. O’Connor, C. T., and T. J. Kiernan. Contemporary management of prosthetic valve endocarditis: principles and future outlook. Expert Rev. Cardiovasc. Ther. 13:501–510, 2015.

    Article  Google Scholar 

  70. Rabkin, E., M. Aikawa, J. R. Stone, Y. Fukumoto, P. Libby, and F. J. Schoen. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 104:2525–2532, 2001.

    Article  Google Scholar 

  71. Rabkin-Aikawa, E., M. Aikawa, M. Farber, J. R. Kratz, G. Garcia-Cardena, N. T. Kouchoukos, et al. Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site. J. Thorac. Cardiovasc. Surg. 128:552–561, 2004.

    Article  Google Scholar 

  72. Rabkin-Aikawa, E., M. Farber, M. Aikawa, and F. J. Schoen. Dynamic and reversible changes of interstitial cell phenotype during development and remodeling of cardiac valves. J. Heart Valve Dis. 13:841–847, 2004.

    Google Scholar 

  73. Rajamannan, N. M., F. J. Evans, E. Aikawa, K. J. Grande-Allen, L. L. Demer, D. D. Heistad, 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. Circulation 124:1783–1791, 2011.

    Article  Google Scholar 

  74. Rashedi, N., and C. M. Otto. Aortic stenosis: changing disease concepts. J. Cardiovasc. Ultrasound 23:59–69, 2015.

    Article  Google Scholar 

  75. Remenyi, B., A. ElGuindy, S. C. Smith, Jr, M. Yacoub, and D. R. Holmes, Jr. Valvular aspects of rheumatic heart disease. Lancet 387:1335–1346, 2016.

    Article  Google Scholar 

  76. Rizzo, S., C. Basso, E. Lazzarini, R. Celeghin, A. Paolin, G, Gerosa, et al. TGF-beta1 pathway activation and adherens junction molecular pattern in nonsyndromic mitral valve prolapse. Cardiovasc. Pathol. 24:359–367, 2015.

    Article  Google Scholar 

  77. Sacks, M. S., and F. J. Schoen. Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves. J. Biomed. Mater. Res. 62:359–371, 2002.

    Article  Google Scholar 

  78. Schoen, F. J. Interventional and Surgical Cardiovascular Pathology: Clinical Correlations and Basic Principles. Philadelphia: WB Saunders, pp. 415, 1989.

    Google Scholar 

  79. Schoen, F. J. Aortic valve structure-function correlations: role of elastic fibers no longer a stretch of the imagination. J. Heart Valve Dis. 6:1–6, 1997.

    Google Scholar 

  80. Schoen, F. J. Pathology of heart valve substitution with mechanical and tissue prostheses. In: Cardiovascular Pathology3rd, edited by M. D. Silver, A. I. Gotlieb, F. J. Schoen, and W. B. Saunders. 2001, pp. 629–677.

    Google Scholar 

  81. Schoen, F. J. Heart valve tissue engineering: quo vadis? Curr. Opin. Biotechnol. 22:698–705, 2011.

    Article  Google Scholar 

  82. Schoen, F. J. Evolving concepts of heart valve dynamics. The continuum of development, functional structure, pathology and tissue engineering. Circulation 118:1864–1880, 2008.

    Article  Google Scholar 

  83. Schoen, F. J. Mechanisms of function and disease in natural and replacement heart valves. Ann. Rev. Pathol. Mech. Dis. 7:161–183, 2012.

    Article  Google Scholar 

  84. Schoen, F. J., and J. Butany. Cardiac valve replacement and related interventions. In: Cardiovascular Pathology4th, edited by L. M. Buja, and J. Butany. Amsterdam: Elsevier, 2016, pp. 529–576.

    Chapter  Google Scholar 

  85. Schoen, F. J., and W. D. Edwards. Valvular heart disease: General principles and stenosis. In: Cardiovascular Pathology3rd, edited by M. D. Silver, A. I. Gotlieb, and F. J. Schoen. Philadelphia: WB Saunders, 2001, pp. 402–442.

    Google Scholar 

  86. Schoen, F. J., Gotlieb, A. I. Heart valve health, disease, replacement, and repair: a 25-year cardiovascular pathology perspective. Cardiovasc. Pathol. 25:341–352, 2016.

    Article  Google Scholar 

  87. Schoen, F. J., and R. J. Levy. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann. Thorac. Surg. 79:1072–1080, 2005.

    Article  Google Scholar 

  88. Schoen, F. J., and R. N. Mitchell. The heart. In: Robbins/Cotran Pathologic Basis of Disease9th, edited by V. Kumar, A. Abbas, and J. C. Aster. Philadelphia: W.B. Saunders, 2015, pp. 523–578.

    Google Scholar 

  89. Schoen, F. J., et al. Pathological considerations in replacement cardiac valves. Cardiovasc. Pathol. 1:29–52, 1992.

    Article  Google Scholar 

  90. Shah, S. R., and N. R. Vyavahare. The effect of glycosaminoglycan stabilization on tissue buckling in bioprosthetic heart valves. Biomaterials 29:1645–1653, 2008.

    Article  Google Scholar 

  91. Sharma, S., A. Mehra, and S. H. Rahimtoola. Valvular heart disease: a century of progress. Am. J. Med. 121:664–673, 2008.

    Article  Google Scholar 

  92. Simon, P., M. T. Kasimir, G. Seebacher, G. Weigel, R. Ullrich, U. Salzer-Muhar, et al. Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. Eur. J. Cardiothorac. Surg. 23:1002–1006, 2003.

    Article  Google Scholar 

  93. Spicer, D. E., J. M. Bridgeman, N. A. Brown, T. J. Mohun, and R. H. Anderson. The anatomy and development of the cardiac valves. Cardiol. Young 24:1008–1022, 2014.

    Article  Google Scholar 

  94. Stephens, E. H., N. de Jonge, M. P. McNeill, C. A. Durst, and K. J. Grande-Allen. Age-related changes in material behavior of porcine mitral and aortic valves and correlation to matrix composition. Tissue Eng. Part A 16:867–878, 2010.

    Article  Google Scholar 

  95. Stollerman, G. H. Rheumatic fever in the 21st century. Clin. Infect. Dis. 33:806–814, 2001.

    Article  Google Scholar 

  96. Torre, M., D. Hwang, R. F. Padera, R. N. Mitchell, and P. A. VanderLaan. Osseous and chondromatous metaplasia in calcific aortic stenosis. Cardiovasc. Pathol. 25:18–24, 2016.

    Article  Google Scholar 

  97. Wirrig, E. E., R. B. Hinton, and K. E. Yutzey. Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves. J. Mol. Cell. Cardiol. 50:561–569, 2011.

    Article  Google Scholar 

  98. Yutzey, K. E., L. L. Demer, S. C. Body, G. S. Huggins, D. A. Towler, C. M. Giachelli, et al. Calcific aortic valve disease: a consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscler. Thromb. Vasc. Biol. 34:2387–2393, 2014.

    Article  Google Scholar 

  99. Zhang, X., B. Xu, D. S. Puperi, A. L. Yonezawa, Y. Wu, H. Tseng, et al. Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering. Acta Biomater. 14:11–21, 2015.

    Article  Google Scholar 

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The author is a paid consultant to: Medtronic, Inc.; Sorin Medical, Inc.; St. Jude Medical, Inc.; Symetis; Xeltis.

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Associate Editors Dr. Hanjoong Jo and Dr. Craig Simmons, Prof. Ajit P. Yoganathan oversaw the review of this article.

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Schoen, F.J. Morphology, Clinicopathologic Correlations, and Mechanisms in Heart Valve Health and Disease. Cardiovasc Eng Tech 9, 126–140 (2018). https://doi.org/10.1007/s13239-016-0277-7

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