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The Influence of Aortic Valve Hemodynamics and LVAD on bio-transport processes in Calcific Aortic Valve Disease

Award Number: R15HL156127
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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The Influence of Aortic Valve Hemodynamics and LVAD on bio-transport processes in Calcific Aortic Valve Disease - Project Summary Calcific Aortic Valve (CAV) is one of the most common types of aortic valve defects, affecting 2–4% of the population above 65 years of age. The biological transport processes near the highly elastic aortic valve (AV) leaflets play an imperative role in the formation of CAV. Despite the significant number of studies on aortic valve hemodynamics, the bio-transport around AV and calcification process is not fully explored. In addition, the ongoing epidemic of advanced heart failure in the U.S. has seen a sharp rise in the utilization of left ventricular assist devices (LVADs) over the last decade. Regardless of technological improvements in the current generation of LVADs, LVAD-supported patients remain prone to AV complications resulting from enormously altered hemodynamics extrinsic to the LVADs. Despite the significant number of studies on altered hemodynamics by LVADs, the cascading effect of hemodynamics alternations on bio-transport processes and CAV is unknown. In this proposed project, we will develop the first computational tool to model Low-Density Lipoprotein (LDL) transport, known as the key component for CAV development, near the highly deforming aortic valve. Our goal is to understand how the movement of the aortic valve leaflets affects the LDL transport and calcification process and how LVADs interact with the LDL transport. We postulate that localized hotspots of LDL concentration near leaflets will not always correlate with the wall shear stress on leaflets and that the spatial and temporal wall shear stress gradient should be considered. We also hypothesize that the elevated transvalvular pressure gradient will increase the localized hotspots of LDL on the aortic side of the valve leaflets and accelerate the CAV development. To test these two hypotheses, the proposed research will include three specific aims. Aim 1 of the proposed research is to develop an innovative immersed boundary method named supreme immersed boundary (SIB). SIB circumnavigates the limitations and deficiencies of existing immersed boundary methods in accurately resolving the velocity and LDL transport boundary layers on highly deforming aortic valve leaflets. In Aim 2, we will test the first hypothesis by modeling the hemodynamics, LDL transport, and mechanical response of the value to examine the correlation between hemodynamic shear stresses and LDL concentration distribution on the moving leaflets. In addition, we will use the LDL concentration level on the leaflets to locally change the stiffness of the leaflets and represent the calcific regions. The biomechanical response of the calcific valve will then be predicted and compared to the healthy valve. In Aim 3, we will test the second hypothesis by including HeartMate III in the model employed in Aim 2. The hemodynamic performance of the valve and LDL transport will be investigated for two pump scenarios (low and high rpm) and two modes (pulse and non-pulse). In this aim, we will also investigate the correlation between LDL and hemodynamic properties, the alternation of hemodynamics and LDL due to the LVAD, calcification pattern, and calcific aortic valve response.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$1 )
2026	2021	UNIVERSITY OF NORTH TEXAS	1112 DALLAS DR STE 4000	DENTON	TX	76205	DENTON	USA	Cardiovascular Diseases Research	000	1	3/23/2026	NEW	-$1
														Subtotal = -$1

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF NORTH TEXAS	1112 DALLAS DR STE 4000	DENTON	TX	76205	DENTON	USA	Cardiovascular Diseases Research	000	1	8/9/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $355,073 )
2021	2021	UNIVERSITY OF NORTH TEXAS	1155 UNION CIR #305250	DENTON	TX	76203	DENTON	USA	Cardiovascular Diseases Research	000	1	7/27/2021	NEW	$355,073
														Subtotal = $355,073

Grand Total All Awards = $355,072

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The Influence of Aortic Valve Hemodynamics and LVAD on bio-transport processes in Calcific Aortic Valve Disease

Award Number: R15HL156127

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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