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A Novel Rheumatic Mitral Valve Disease Model with Ex Vivo Hemodynamic and Biomechanical Validation

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Abstract

Purpose

Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics.

Methods

Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n = 4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n = 18).

Results

The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p < 0.001), reduced effective orifice areas (p < 0.001), augmented transmitral mean gradients (p < 0.001), and increased leaflet stiffness (p = 0.025).

Conclusion

This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.

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Data Availability

All data is made available in this manuscript.

Code Availability

Not required.

Abbreviations

RHD:

Rheumatic heart disease

MV:

Mitral valve

3D:

Three-dimensional

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Acknowledgments

This work was supported by the National Institutes of Health (NIH R01 HL152155-03, YJW), the National Science Foundation Graduate Research Fellowship Program (DGE-1656518, AMI), the Stanford Graduate Fellowship (AMI), and the Thoracic Surgery Foundation Resident Research Fellowship (YZ). We would also like to thank the generous donation by Donald and Sally O’Neal to support this research effort.

Funding

This work was supported by the National Institutes of Health (NIH R01 HL152155-03 YJW), the National Science Foundation Graduate Research Fellowship Program (DGE-1656518, AMI), the Stanford Graduate Fellowship (AMI), and the Thoracic Surgery Foundation Resident Research Fellowship (YZ).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Stanford University, Falk Cardiovascular Research Building CV-235, 300 Pasteur Drive, Stanford, CA, 94305-5407, USA

    Matthew H. Park, Pearly K. Pandya, Yuanjia Zhu, Danielle M. Mullis, Hanjay Wang, Annabel M. Imbrie-Moore, Robert Wilkerson, Mateo Marin-Cuartas & Y. Joseph Woo

  2. Department of Mechanical Engineering, Stanford University, Stanford, CA, USA

    Matthew H. Park, Pearly K. Pandya & Annabel M. Imbrie-Moore

  3. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Yuanjia Zhu & Y. Joseph Woo

  4. University Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany

    Mateo Marin-Cuartas

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Park, M.H., Pandya, P.K., Zhu, Y. et al. A Novel Rheumatic Mitral Valve Disease Model with Ex Vivo Hemodynamic and Biomechanical Validation. Cardiovasc Eng Tech 14, 129–140 (2023). https://doi.org/10.1007/s13239-022-00641-3

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