Noncoaxial Transcatheter Aortic Valve Deployment Creates Cusp-Specific Thrombogenic Microenvironments Through Altered Sinus Hemodynamics

Background: Transcatheter aortic valve replacement has transformed the management of aortic stenosis; however, adverse outcomes such as leaflet thrombosis and hypoattenuating leaflet thickening remain clinically significant concerns. Flow disturbances resulting from valve canting may alter local hemodynamics and promote thrombogenic conditions. We investigated how modest transcatheter heart valve canting alters cusp-specific sinus flow and washout and promotes localized thrombogenic microenvironments associated with leaflet surface thrombus formation using particle image velocimetry, a physiologic blood loop, and tissue analysis. Methods: A patient-derived aortic root model was used to evaluate the hemodynamic and thrombogenic effects of THV canting at -10° (anti-curvature), 0° (neutral), and +10° (along-curvature). High-resolution particle image velocimetry quantified sinus flow fields and washout characteristics, and complementary whole-blood loop experiments enabled histologic assessment of leaflet-associated thrombus formation. Results: ) washout to 4.7 cycles versus 2.9 and 1.8 cycles, respectively. Histology localized surface-adherent platelet/fibrin thrombus to these poorly washed regions, most prominently on the right coronary cusp leaflet in anti-curvature deployments. Left and noncoronary cusp responses shifted with tilt direction, indicating redistribution rather than uniform worsening of thrombogenic conditions. Conclusions: Even modest noncoaxial deployment is sufficient to create sinus-resolved throm-bogenic microenvironments that are not captured by global gradient or effective orifice area. Deployment configuration is therefore a modifiable determinant of post-TAVR leaflet throm-bosis risk and may contribute to HALT.

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Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-21
DOI
https://doi.org/10.64898/2026.04.17.719323
Primary Topic
Cardiac Valve Diseases and Treatments
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article
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article

Noncoaxial Transcatheter Aortic Valve Deployment Creates Cusp-Specific Thrombogenic Microenvironments Through Altered Sinus Hemodynamics

Akshita Jha, Lakshmi Prasad Dasi, Joseph E. Aslan, Thangam Natarajan et al.
bioRxiv (Cold Spring Harbor Laboratory)
Cardiac Valve Diseases and Treatments
article

Noncoaxial Transcatheter Aortic Valve Deployment Creates Cusp-Specific Thrombogenic Microenvironments Through Altered Sinus Hemodynamics

Akshita Jha, Lakshmi Prasad Dasi, Joseph E. Aslan, Thangam Natarajan, Stephanie Sellers, Monica T. Hinds, Ajit P. Yoganathan, Cole Baker, Christian D Salgado, Jae Hyun Kim
article en

Abstract

Background: Transcatheter aortic valve replacement has transformed the management of aortic stenosis; however, adverse outcomes such as leaflet thrombosis and hypoattenuating leaflet thickening remain clinically significant concerns. Flow disturbances resulting from valve canting may alter local hemodynamics and promote thrombogenic conditions. We investigated how modest transcatheter heart valve canting alters cusp-specific sinus flow and washout and promotes localized thrombogenic microenvironments associated with leaflet surface thrombus formation using particle image velocimetry, a physiologic blood loop, and tissue analysis. Methods: A patient-derived aortic root model was used to evaluate the hemodynamic and thrombogenic effects of THV canting at -10° (anti-curvature), 0° (neutral), and +10° (along-curvature). High-resolution particle image velocimetry quantified sinus flow fields and washout characteristics, and complementary whole-blood loop experiments enabled histologic assessment of leaflet-associated thrombus formation. Results: ) washout to 4.7 cycles versus 2.9 and 1.8 cycles, respectively. Histology localized surface-adherent platelet/fibrin thrombus to these poorly washed regions, most prominently on the right coronary cusp leaflet in anti-curvature deployments. Left and noncoronary cusp responses shifted with tilt direction, indicating redistribution rather than uniform worsening of thrombogenic conditions. Conclusions: Even modest noncoaxial deployment is sufficient to create sinus-resolved throm-bogenic microenvironments that are not captured by global gradient or effective orifice area. Deployment configuration is therefore a modifiable determinant of post-TAVR leaflet throm-bosis risk and may contribute to HALT.

bioRxiv (Cold Spring Harbor Laboratory)
Oregon National Primate Research Center (US), Valve (United States) (US), Oregon Health & Science University (US), The Wallace H. Coulter Department of Biomedical Engineering (US), Centre for Social Innovation (CA)
Openalex Percentile: Top 19%
Cardiac Valve Diseases and Treatments
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