Background. Although our comprehension of nonrheumatic aortic stenosis (NRAS) has increased substantially during the last decade, less is known about the histopathology of rheumatic aortic stenosis (RAS). The aim of this study was to investigate rheumatic aortic stenosis by means of analyses previously used in nonrheumatic stenosis. Material and Methods. Valve specimens were obtained from 39 patients referred to hospital due to significant aortic stenosis. According to established macroscopic criteria the valves were divided into two groups consisting of 29 NRAS and 10 RAS valves. Mononuclear inflammatory cells and apolipoproteins were investigated using immunohistochemical analyses. Results. The localisation of calcification differed in tricuspid nonrheumatic valves when compared to bicuspid nonrheumatic and rheumatic valves. The RAS valves revealed a lower degree of T lymphocyte infiltration compared with the NRAS valves. Infiltration of macrophages was seen in all valves and there were no differences regarding deposition of apolipoprotein. Conclusion. Rheumatic and nonrheumatic aortic stenotic valves show a similar and significant chronic inflammation. The similarities regarding the localisation of calcification indicate that the valve anomaly/morphology can influence the pathogenesis of aortic stenosis. Finally, our findings highlight the question of a postinflammatory valvular disease of other causes than rheumatic fever. 1. Introduction At the beginning of the 20th century, the incidence of rheumatic fever in the United States exceeded 100 per 100,000 population [1], and rheumatic heart disease was consequently the leading cause of heart valve illness. During the same century a gradual decrease in the incidence of rheumatic fewer was seen. The incidence ranged between 40 and 65 per 100,000 between 1935 and 1960 and is currently estimated at less than 2 per 100,000. Improved socioeconomic conditions in the western world during the late half of the 20th century, with an increased life span, dramatically changed the aetiologic panorama of aortic stenosis. The so-called degenerative, nonrheumatic aortic stenosis (NRAS) has become the foremost cause of significant aortic valve obstruction. In adults undergoing aortic valve replacement for symptomatic aortic stenosis in the USA, nonrheumatic tricuspid aortic stenosis (NRAS-T) accounts for 51% of cases, bicuspid aortic stenosis (NRAS-B) for 36%, and rheumatic aortic stenosis (RAS) for 9% [2]. However, the presence of an aortic stenosis of rheumatic origin has been under debate. The sole pathognomonic
References
[1]
A. S. Dajani, “Rheumatic fever,” in Braunwald's Heart Disease, D. P. Zipes, R. O. Bonow, and D. L. Mann, Eds., vol. 2, pp. 2093–2099, Elsevier Saunders, St. Louis, Mo, USA, 7th edition, 2005.
[2]
A. J. Dare, J. P. Veinot, W. D. Edwards, H. D. Tazelaar, and H. V. Schaff, “New observations on the etiology of aortic valve disease: a surgical pathologic study of 236 cases from 1990,” Human Pathology, vol. 24, no. 12, pp. 1330–1338, 1993.
[3]
P. Gallo, E. Tonelli, B. Marino et al., “Postinflammatory scarring of cardiac valves of rheumatic and nonrheumatic etiology,” The American Journal of Cardiovascular Pathology, vol. 3, no. 2, pp. 101–105, 1990.
[4]
Y. A. Goffin, J. L. Leclerc, and G. C. Primo, “Histopathology of the aortic valve in patients with a previous history of acute rheumatic fever. An analysis of 63 surgical specimens,” Acta Cardiologica, vol. 39, no. 5, pp. 329–339, 1984.
[5]
W. C. Roberts, “Anatomically isolated aortic valvular disease. The case against its being of rheumatic etiology,” The The American Journal of Medicine, vol. 49, no. 2, pp. 151–159, 1970.
[6]
W. C. Roberts, “The structure of the aortic valve in clinically isolated aortic stenosis: an autopsy study of 162 patients over 15 years of age,” Circulation, vol. 42, no. 1, pp. 91–97, 1970.
[7]
K. D. O'Brien, J. Kuusisto, D. D. Reichenbach et al., “Osteopontin is expressed in human aortic valvular lesions,” Circulation, vol. 92, no. 8, pp. 2163–2168, 1995.
[8]
K. D. O'Brien, D. D. Reichenbach, S. M. Marcovina, J. Kuusisto, C. E. Alpers, and C. M. Otto, “Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of “degenerative” valvular aortic stenosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 16, no. 4, pp. 523–532, 1996.
[9]
M. Olsson, C. J. Dalsgaard, A. Haegerstrand, M. Rosenqvist, L. Ryden, and J. Nilsson, “Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves,” Journal of the American College of Cardiology, vol. 23, no. 5, pp. 1162–1170, 1994.
[10]
M. Olsson, M. Rosenqvist, and J. Nilsson, “Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis,” Journal of the American College of Cardiology, vol. 24, no. 7, pp. 1664–1671, 1994.
[11]
M. Olsson, J. Thyberg, and J. Nilsson, “Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 5, pp. 1218–1222, 1999.
[12]
C. M. Otto, J. Kuusisto, D. D. Reichenbach, A. M. Gown, and K. D. O'Brien, “Characterization of the early lesion of “degenerative” valvular aortic stenosis: histological and immunohistochemical studies,” Circulation, vol. 90, no. 2, pp. 844–853, 1994.
[13]
L. Wallby, B. Janerot-Sj？berg, T. Steffensen, and M. Broqvist, “T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves,” Heart, vol. 88, no. 4, pp. 348–351, 2002.
[14]
W. Lars, S. Thora, and B. Mats, “Role of inflammation in nonrheumatic, regurgitant heart valve disease. A comparative, descriptive study regarding apolipoproteins and inflammatory cells in nonrheumatic heart valve disease,” Cardiovascular Pathology, vol. 16, no. 3, pp. 171–178, 2007.
[15]
A. Pomerance, “Pathogenesis of aortic stenosis and its relation to age,” The British Heart Journal, vol. 34, no. 6, pp. 569–574, 1972.
[16]
F. J. Schoen, “Surgical pathology of removed natural and prosthetic heart valves,” Human Pathology, vol. 18, no. 6, pp. 558–567, 1987.
[17]
R. Subramanian, L. J. Olson, and W. D. Edwards, “Surgical pathology of pure aortic stenosis: a study of 374 cases,” Mayo Clinic Proceedings, vol. 59, no. 10, pp. 683–690, 1984.
[18]
N. Stratford, K. Britten, and P. Gallagher, “Inflammatory infiltrates in human coronary atherosclerosis,” Atherosclerosis, vol. 59, no. 3, pp. 271–276, 1986.
[19]
B. Waller, J. Howard, and S. Fess, “Pathology of aortic valve stenosis and pure aortic regurgitation. A clinical morphologic assessment—part I,” Clinical Cardiology, vol. 17, no. 2, pp. 85–92, 1994.
[20]
C. S. Passik, D. M. Ackermann, J. R. Pluth, and W. D. Edwards, “Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases,” Mayo Clinic Proceedings, vol. 62, no. 2, pp. 119–123, 1987.
[21]
E. G. J. Olsen, The Pathology of the Heart, The Macmillan Press, London, UK, 2nd edition, 1980.
[22]
F. Schoen and M. Sutton, “Contemporary pathologic considerations in valvular heart disease,” in Cardiovascular Pathology, R. Virmani, J. Atkinson, and J. Fenoglio, Eds., pp. 334–353, WB Saunders, Philadelphia, Pa, USA, 1991.
[23]
P. Chopra and M. L. Bhatia, “Chronic rheumatic heart disease in India: a reappraisal of pathologic changes,” The Journal of Heart Valve Disease, vol. 1, no. 1, pp. 92–101, 1992.
[24]
P. Chopra, H. D. Tandon, V. Raizada, N. Gopinath, C. Butler, and R. C. Williams Jr., “Comparative studies of mitral valves in rheumatic heart disease,” Archives of Internal Medicine, vol. 143, no. 4, pp. 661–666, 1983.
[25]
V. Raizada, R. C. Williams Jr., P. Chopra et al., “Tissue distribution of lymphocytes in rheumatic heart valves as defined by monoclonal anti-T cell antibodies,” The American Journal of Medicine, vol. 74, no. 1, pp. 90–96, 1983.
[26]
U. Baandrup, “Rheumatic fever reappraised,” Chinese Medical Journal, vol. 118, no. 5, pp. 360–361, 2005.
[27]
Z. G. Pan, X. N. Wang, Y. W. Li, H. Y. Zhang, and L. C. Archard, “Detection of herpes simplex virus type 1 in rheumatic valvular tissue,” Chinese Medical Journal, vol. 118, no. 5, pp. 370–376, 2005.
[28]
Y. Soini, T. Salo, and J. Satta, “Angiogenesis is involved in the pathogenesis of nonrheumatic aortic valve stenosis,” Human Pathology, vol. 34, no. 8, pp. 756–763, 2003.
[29]
J. M. Isner, S. K. Chokshi, A. DeFranco, J. Braimen, and G. A. Slovenkai, “Contrasting histoarchitecture of calcified leaflets from stenotic bicuspid versus stenotic tricuspid aortic valves,” Journal of the American College of Cardiology, vol. 15, no. 5, pp. 1104–1108, 1990.
[30]
F. E. M. G. Vollebergh and A. E. Becker, “Minor congenital variations of cusp size in tricuspid aortic valves. Possible link with isolated aortic stenosis,” The British Heart Journal, vol. 39, no. 9, pp. 1006–1011, 1977.
[31]
G. K. Hansson, “Mechanisms of disease: inflammation, atherosclerosis, and coronary artery disease,” The New England Journal of Medicine, vol. 352, no. 16, pp. 1685–1695, 2005.
[32]
E. R. Mohler III, “Are atherosclerotic processes involved in aortic-valve calcification?” The Lancet, vol. 356, no. 9229, pp. 524–525, 2000.
