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Etiology of degenerative disease of the tri-leaflet aortic valve: a simple explanation for a complex problem
1Carolinas Heart Institute, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC 28203, USA.
Insights
Degenerative aortic valve disease may not be atherosclerosis. Loss of aortic wall compliance causes mechanical stress on aortic leaflets, leading to valve degeneration and calcification.
Area of Science:
- Cardiovascular Science
- Biomedical Engineering
- Pathology
Background:
- Aortic valve disease shares risk factors with aortic wall atherosclerosis, leading to the prevailing view that they are etiologically similar.
- Degenerative aortic valve disease is often considered a manifestation of aortic atherosclerosis affecting the valve leaflets.
- This perspective overlooks the unique functional and structural properties of the aortic valve apparatus.
Purpose of the Study:
- To challenge the prevailing view that degenerative aortic valve disease is solely atherosclerosis of the aortic valve.
- To investigate the mechanical and structural interactions between the aortic wall and the aortic valve leaflets.
- To elucidate the role of aortic wall compliance in the pathogenesis of aortic valve degeneration.
Main Methods:
- Analysis of the functional properties of the aortic valve as a composite structure.
- Experimental studies demonstrating the impact of reduced aortic wall compliance on aortic leaflet mechanics.
- Investigation of the sequence of events from mechanical stress to leaflet microstructure damage, sclerosis, and calcification.
Main Results:
- Loss of aortic wall compliance in the sinuses induces significant flexion stress on the aortic leaflets.
- This mechanical stress initiates a cascade leading to microstructural damage, sclerosis, and eventual cusp distortion or calcification.
- The "pull-and-release" mechanism's dysfunction may contribute to both native and bioprosthetic aortic valve degeneration.
Conclusions:
- Degenerative aortic valve disease may arise from mechanical factors related to aortic wall compliance rather than being a direct form of atherosclerosis.
- Aortic wall mechanics play a critical role in maintaining aortic valve integrity.
- Understanding these mechanical interactions is crucial for developing effective treatments for aortic valve degeneration and improving bioprosthetic valve durability.
Abstract:
Risk factors for both atherosclerotic aortic wall disease and degenerative disease of the tri-leaflet aortic valve are very similar if not identical. This correlation grows even stronger as the person advances in years. Because of this, it is the prevailing view that sclerosis of the tri-leaflet aortic valve is a disease similar in etiology with sclerosis of the aortic wall. In other words, degenerative aortic valve disease is atherosclerosis of the aortic valve. Our studies challenge these views. The aortic valve is a functional assembly composed of the three cusps, corresponding sinuses, and the sinotubular junction, characterized not only by morphological features but also its functional properties, which together create an environment that is optimal for distribution of diastolic pressure load, and assures proper and timely valve opening and closure. Our experiments also demonstrate that loss of aortic wall compliance at the level of the sinuses leads to significant flexion stress in the aortic leaflets and it is likely to start a chain of events, which begins with mechanical damage to the leaflet microstructure then continues to more evident sclerosis, and finally ends in gross distortion and/or calcification of the cusps. The loss of the "pull-and-release" process may also play a part in disintegration of bioprosthetic valves and in degeneration of native aortic valves encased in non-compliant prostheses.
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