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Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations

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Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85 m s−1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.

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Acknowledgments

This work is supported by NIH-NIBIB BRP U03EB026414 grant. Author RHA acknowledges the support of the Nathan Cummings Chair of Mechanics. Author AM acknowledges the support of the Planning and Budgeting Committee – Israeli Council for Higher Education.

Conflicts of Interest

Authors KL and RH are employees of Edwards Lifesciences Ltd. Author DB has an equity interest in Polynova Cardiovascular Inc. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel

    Karin Lavon, Adi Morany, Rotem Halevi & Rami Haj-Ali

  2. Department of Cardiology, Rabin Medical Center, Petach Tikva, Israel

    Ashraf Hamdan

  3. Department of Cardio-Thoracic Surgery, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Ehud Raanani

  4. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA

    Danny Bluestein & Rami Haj-Ali

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  1. Karin Lavon
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  2. Adi Morany
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Correspondence to Rami Haj-Ali.

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Associate Editor Stefan M. Duma oversaw the review of this article.

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Lavon, K., Morany, A., Halevi, R. et al. Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations. Ann Biomed Eng 49, 3310–3322 (2021). https://doi.org/10.1007/s10439-021-02877-x

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