Ilya V Egorov*

Doctor of Medicine, Professor, Head of the Department of Family Medicine, Institute of Integrative Family Therapy, Moscow, Russia

*Corresponding Author: Ilya V Egorov, Doctor of Medicine, Professor, Head of the Department of Family Medicine, Institute of Integrative Family Therapy, Moscow, Russia.

Received: September 05, 2024; Published: October 08, 2024

Abstract

In recent decades, there has been a shift in the understanding of aortic stenosis that develops in elderly and older individuals. In Russia, this condition has been traditionally associated with atherosclerosis, while internationally, since the first description by J.G. Mönckeberg (1904), this heart defect has been interpreted as degenerative, resulting from wear and tear of the aortic valve followed by dystrophic petrification. However, even this concept is now considered outdated. New data have highlighted the process in the aortic valve as an active inflammation, a nosologically distinct disease. The role of cellular, particularly lymphocytic, infiltration, genetic predisposition to pathological fibrosis in the valve, specific endothelial damage, activation of mechanisms of ectopic ossification, and more, have been demonstrated. The link with osteoporosis has also become evident. Interest in "Mönckeberg's disease" is further fueled by the belief among pharmacologists that it is feasible to develop methods for preventing the calcification of intracardiac structures. However, this is a matter for the future. Currently, in everyday practice, doctors still lack guidelines for managing patients with senile aortic stenosis. This review is dedicated to addressing this issue.

 Keywords: Calcified Aortic Stenosis; Osteoporosis; Bicuspid Aortic Valve; Angiotensin-Converting Enzyme Inhibitors

References

1. Awan Z., et al. “Vascular calcifications in homozygote familial hypercholesterolemia”. Arteriosclerosis, Thrombosis, and Vascular Biology 4 (2008): 777-785.
2. Moncla LHM., et al. “Calcific aortic valve disease: mechanisms, prevention and treatment”. Nature Reviews Cardiology 20 (2023): 546-559.
3. Mönckeberg JG. “Der normale histologische Bau und die Sklerose Aortenklappen”. Virchows Archiv fur pathologische Anatomie und Physiology und fur Klinische Medizin 176 (1904): 472-496
4. Olsson M., et al. “Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves”. Journal of the American College of Cardiology 23 (1994): 1162-1170.
5. Wallby L., et al. “T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves”. Heart 88 (2002): 348-351.
6. Yu M., et al. “Insights into the Inherited Basis of Valvular Heart Disease”. Current Cardiology Report 5 (2024): 381-392.
7. Beppu S., et al. “Rapidity of progression of aortic stenosis in patients with congenital bicuspid aortic valves”. American Journal of Cardiology 71 (1993): 322-327.
8. Gollmann-Tepeköylü С., et al. “Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact”. Interactive CardioVascular and Thoracic Surgery6 (2022).
9. Otto CM., et al. “Characterization of the early lesion in “degenerative” valvular aortic stenosis: histological and immunohistochemical studies”. Circulation 90 (1994): 844-853.
10. Qin M., et al. “Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease”. Frontiers on Cardiovascular Medicine 9 (2023): 1058274.
11. Kaden JJ., et al. “Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis”. Atherosclerosis 170 (2003): 205-211.
12. Tanase DM., et al. “Contribution of Oxidative Stress (OS) in Calcific Aortic Valve Disease (CAVD): From Pathophysiology to Therapeutic Targets”. Cells17 (2022): 2663.
13. Egorov IV. “Pathogenetic aspects of senile aortic stenosis”. Russian Medical Journal 3 (2003): 48-52.
14. O’Brien KD., et al. “Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma”. Circulation 106 (2002): 2224-2230.
15. Grau JB., et al. “Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease”. Annals of Thoracal Surgery 93 (2012): 79-86.
16. Sivaguru M., et al. “Osteopontin stabilization and collagen containment slows amorphous calcium phosphate transformation during human aortic valve leaflet calcification”. Scientific Report1 (2024): 12222.
17. Perrotta I., et al. “New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review”. Histopathology 59 (2011): 504-513.
18. Gössl M., et al. “Role of circulating osteogenic progenitor cells in calcific aortic stenosis”. Journal of the American College of Cardiology60.19 (2012): 1945-1953.
19. Bairati F and DeBiasi S. “Presence of a smooth muscle system in aortic valve leaflets”. Anatomy and Embryology 3 (1981): 329-340.
20. Mohler ER., et al. “Bone formation and inflammation in cardiac valves”. Circulation 103 (2001): 1522-1528.
21. Alexopoulos A., et al. “Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves”. International Journal of Cardiology139.2 (2010): 142-149.
22. Arumugam SB., et al. “Osseous metaplasia with functioning marrow in a calcified aortic valve”. Journal of Cardiology Surgery5 (1995): 610-61120.
23. Urena P., et al. “Evolutive aortic stenosis in hemodialysis patients: analysis of risk factors”. Nephrologie 20 (1999): 217-225.
24. Karpova NYu., et al. “Calcined aortic stenosis and osteoporosis: general mechanisms and prospects of pharmacological correction”. 5.2 (2011): 86-93.
25. Mohler ER., et al. “Development and progression of aortic valve stenosis: atherosclerosis risk factors—a causal relationship? A clinical morphologic study”. Clinical Cardiology 14 (1991): 995-999.
26. Peltier M., et al. “Relation between cardiovascular risk factors and nonrheumatic severe calcific aortic stenosis among patients with a three-cuspid aortic valve”. American Journal of Cardiology 91 (2003): 97-99.
27. Chen Y., et al. “Calcified aortic valve disease complicated with and without diabetes mellitus: the underlying pathogenesis”. Reviews in Cardiovascular Medicine 1 (2022): 7.
28. Aronow WS., et al. “Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis”. American Journal of Cardiology 83 (1999): 599-600.
29. Olsen MH., et al. “Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy)”. American Journal of Cardiology 95 (2005): 132-136.
30. Chandra HR., et al. “Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation”. Journal of the American College of Cardiology 43 (2004): 169-175.
31. Hu T., et al. “Investigation of autophagy‑related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation”. Experimental and Therapeutic Medicine 5 (2024): 233.
32. Cosmi JE., et al. “The risk of the development of aortic stenosis in patients with “benign” aortic valve thickening”. Archives Internal Medicine 162 (2002): 2345-2347.
33. Otto CM., et al. “Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly”. The New England Journal of Medicine 341 (1999): 142-147.
34. Roger VL., et al. “Progression of aortic stenosis in adults: new appraisal using Doppler echocardiography”. American Heart Journal 119 (1990) 331-338.
35. Rosenhek R., et al. “Predictors of outcome in severe, asymptomatic aortic stenosis”. The New England Journal of Medicine 343 (2000): 611-617.
36. Egorov IV and Shostak NA. “Degenerative aortic stenosis: a modern view of an old problem”. Clinical Gerontology 11-12 (2000): 37-42.
37. Horstkotte D and Loogen F. “The natural history of aortic valve stenosis”. European Heart Journal 9 (1988): 57-64.
38. Turina J., et al. “Spontaneous course of aortic valve disease”. European Heart Journal 8 (1987): 471-483.
39. Otto MC., et al. “2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines”. Circulation 5 (2021): e35-e71.
40. Gerber IL., et al. “Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis”. Circulation 107 (2003): 1884-1890.
41. Bergler-Klein J., et al. “Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis”. Circulation 109 (2004): 2303-2308.
42. Bohbot Y., et al. “Usefulness of Cardiac Magnetic Resonance Imaging in Aortic Stenosis”. Circular Cardiovascular Imaging5 (2020): e010356.
43. Chrysostomidis G., et al. “The Application of Precision Medicine in Structural Heart Diseases: A Step towards the Future”. Journal of Personalized Medicine 4 (2024): 375.
44. Cawley PJ and Otto CM. “Prevention of calcific aortic valve stenosis-fact or fiction?”. Annals of Medicine2 (2009): 100-108.
45. Benton JA., et al. “Statins block calcific nodule formation of valvular interstitial cells by inhibiting alpha-smooth muscle actin expression”. Arteriosclerosis, Thrombosis, and Vascular Biology11 (2009): 1950-1957.
46. Parolari A., et al. “Do statins improve outcomes and delay the progression of non-rheumatic calcific aortic stenosis?”. Heart 7 (2011): 523-529.
47. Goldstein RE. “Bone modifiers and the quest to slow progression of aortic stenosis”. American Journal of Cardiology104.1 (2009): 125-127.
48. Elder DH., et al. “Aortic valvular heart disease: Is there a place for angiotensin-converting-enzyme inhibitors?”. Expert Review of Cardiovascular Therapy1 (2013): 107-114.
49. Nadir MA., et al. “Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis”. Journal of the American College of Cardiology58 (2011): 570-576.
50. Jiménez-Candil J., et al. “Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study”. Heart 10 (2005): 1311-1318.

Citation

Citation: Ilya V Egorov. “Calcified Aortic Stenosis: From Understanding Pathogenesis to the Development of a Conservative Treatment Strategy (on the 120^th Anniversary of the Publication of J.G. Mönckeberg)”.Acta Scientific Medical Sciences 8.11 (2024): 17-24.

Copyright

Copyright: © 2024 Ilya V Egorov. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.