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Published on: May 10, 2021
Computational Model for Early-Stage Aortic Valve Calcification Shows Hemodynamic Biomarkers
Asad Mirza1, Chia-Pei Denise Hsu1, Andres Rodriguez1
1Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA.
Insights
Tracking hemodynamics may offer a new way to monitor early-stage heart valve calcification. This study found increased wall shear stress in calcified bioscaffold valves, suggesting a potential biomarker for calcific aortic valve disease (CAVD).
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Medical Engineering
Background:
- Heart disease remains a leading cause of mortality globally.
- Calcific aortic valve disease (CAVD) is the most common form, necessitating early detection for effective patient management.
- Predictive markers for early CAVD are crucial for timely intervention before aortic valve replacement surgery.
Purpose of the Study:
- To investigate hydrodynamic, mechanical, and hemodynamic differences between healthy and early-stage calcified porcine small intestinal submucosa (PSIS) bioscaffold valves.
- To identify potential parameters for tracking CAVD progression.
- To assess the suitability of PSIS bioscaffolds for modeling early CAVD.
Main Methods:
- Three groups of PSIS valves were tested: raw (control), calcified (seeded with VICs/VECs) in static conditions, and calcified (seeded with VICs/VECs) in bioreactor oscillatory flow.
- Hydrodynamic assessments and mechanical testing (Young's modulus) were performed.
- Fluid-structure interaction (FSI) simulations were conducted to analyze hemodynamic parameters like time-averaged wall shear stress (TAWSS).
Main Results:
- Hydrodynamic metrics in calcified valves were below thresholds for mild calcification.
- A significant increase in Young's modulus was observed in calcified valves compared to raw PSIS, indicating altered tissue structure.
- FSI simulations showed a significant increase in TAWSS in calcified valve groups compared to the raw control group.
Conclusions:
- While hydrodynamic metrics were not indicative of early calcification, increased mechanical stiffness (Young's modulus) suggests structural changes.
- Fluid-structure interaction simulations revealed a significant increase in time-averaged wall shear stress (TAWSS) in calcified valves.
- Hemodynamic monitoring, specifically TAWSS, may serve as a viable biomarker for early-stage calcific aortic valve disease (CAVD) tracking.
Abstract:
Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes. Three valve groups were tested: raw PSIS as a control and two calcified groups that were seeded with human valvular interstitial and endothelial cells (VICs/VECs) and cultivated in calcifying media. These two calcified groups were cultured in either static or bioreactor-induced oscillatory flow conditions. Hydrodynamic assessments showed metrics were below thresholds associated for even mild calcification. Young's modulus, however, was significantly higher in calcified valves when compared to raw PSIS, indicating the morphological changes to the tissue structure. Fluid-structure interaction (FSI) simulations agreed well with hydrodynamic results and, most notably, showed a significant increase in time-averaged wall shear stress (TAWSS) between raw and calcified groups. We conclude that tracking hemodynamics may be a viable biomarker for early-stage CAVD tracking.
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