Visions of TAVR Future: Development and Optimization of a Second Generation Novel Polymeric TAVR.

Tissue-based transcatheter aortic valve (AV) replacement (TAVR) devices have been a breakthrough approach for treating aortic valve stenosis. However, with the expansion of TAVR to younger and lower risk patients, issues of long-term durability and thrombosis persist. Recent advances in polymeric valve technology facilitate designing more durable valves with minimal in vivo adverse reactions. We introduce our second-generation polymeric transcatheter aortic valve (TAV) device, designed and optimized to address these issues. We present the optimization process of the device, wherein each aspect of device deployment and functionality was optimized for performance, including unique considerations of polymeric technologies for reducing the volume of the polymer material for lower crimped delivery profiles. The stent frame was optimized to generate larger radial forces with lower material volumes, securing robust deployment and anchoring. The leaflet shape, combined with varying leaflets thickness, was optimized for reducing the flexural cyclic stresses and the valve's hydrodynamics. Our first-generation polymeric device already demonstrated that its hydrodynamic performance meets and exceeds tissue devices for both ISO standard and patient-specific in vitro scenarios. The valve already reached 900 × 106 cycles of accelerated durability testing, equivalent to over 20 years in a patient. The optimization framework and technology led to the second generation of polymeric TAV design- currently undergoing in vitro hydrodynamic testing and following in vivo animal trials. As TAVR use is rapidly expanding, our rigorous bio-engineering optimization methodology and advanced polymer technology serve to establish polymeric TAV technology as a viable alternative to the challenges facing existing tissue-based TAV technology.

Thrombogenic Risk Assessment of Transcatheter Prosthetic Heart Valves Using a Fluid-Structure Interaction Approach.

Background and Objective: Prosthetic heart valve interventions such as TAVR have surged over the past decade, but the associated complication of long-term, life-threatening thrombotic events continues to undermine patient outcomes. Thus, improving thrombogenic risk analysis of TAVR devices is crucial. In vitro studies for thrombogenicity are typically difficult to perform. However, revised ISO testing standards include computational testing for thrombogenic risk assessment of cardiovascular implants. We present a fluid-structure interaction (FSI) approach for assessing thrombogenic risk of prosthetic heart valves. Methods: An FSI framework was implemented via the incompressible computational fluid dynamics multi-physics solver of the Ansys LS-DYNA software. The numerical modeling approach for flow analysis was validated by comparing the derived flow rate of the 29-mm CoreValve device from benchtop testing and orifice areas of commercial TAVR valves in the literature to in silico results. Thrombogenic risk was analyzed by computing stress accumulation (SA) on virtual platelets seeded in the flow fields via Ansys EnSight. The integrated FSI-thrombogenicity methodology was subsequently employed to examine hemodynamics and thrombogenic risk of TAVR devices with two approaches: 1) engineering optimization and 2) clinical assessment. Results: The simulated effective orifice areas of the commercial devices were in the range reported in the literature. The flow rates from the in vitro flow testing matched well with the in silico results. The approach was used to analyze the effect of various TAVR leaflet designs on hemodynamics. Platelets experienced different magnitudes of SA along their trajectories as they flowed past each design. Post-TAVR deployment hemodynamics in patient-specific bicuspid aortic valve anatomies revealed varying degrees of thrombogenic risk for these patients, despite being clinically defined as "mild" paravalvular leak. Conclusions: Our methodology can be used to improve the thromboresistance of prosthetic valves from the initial design stage to the clinic. It allows for unparalleled optimization of devices, uncovering key TAVR leaflet design parameters that can be used to mitigate thrombogenic risk, in addition to patient-specific modeling to evaluate device performance. This work demonstrates the utility of advanced in silico analysis of TAVR devices that can be utilized for thrombogenic risk assessment of other blood recirculating devices.

Thrombogenic Risk Assessment of Transcatheter Prosthetic Heart Valves Using a Fluid-Structure Interaction Approach.

BACKGROUND AND OBJECTIVE: Prosthetic heart valve interventions such as TAVR have surged over the past decade, but the associated complication of long-term, life-threatening thrombotic events continues to undermine patient outcomes. Thus, improving thrombogenic risk analysis of TAVR devices is crucial. In vitro studies for thrombogenicity are typically difficult to perform. However, revised ISO testing standards include computational testing for thrombogenic risk assessment of cardiovascular implants. We present a fluid-structure interaction (FSI) approach for assessing thrombogenic risk of transcatheter aortic valves. METHODS: An FSI framework was implemented via the incompressible computational fluid dynamics multi-physics solver of the ANSYS LS-DYNA software. The numerical modeling approach for flow analysis was validated by comparing the derived flow rate of the 29 mm CoreValve device from benchtop testing and orifice areas of commercial TAVR valves in the literature to in silico results. Thrombogenic risk was analyzed by computing stress accumulation (SA) on virtual platelets seeded in the flow fields via ANSYS EnSight. The integrated FSI-thrombogenicity methodology was subsequently employed to examine hemodynamics and thrombogenic risk of TAVR devices with two approaches: 1) engineering optimization and 2) clinical assessment. RESULTS: Simulated effective orifice areas for commercial valves were in reported ranges. In silico cardiac output and flow rate during the positive pressure differential period matched experimental results by approximately 93 %. The approach was used to analyze the effect of various TAVR leaflet designs on hemodynamics, where platelets experienced instantaneous stresses reaching around 10 Pa. Post-TAVR deployment hemodynamics in patient-specific bicuspid aortic valve anatomies revealed varying degrees of thrombogenic risk with the highest median SA around 70 dyn·s/cm2 - nearly double the activation threshold - despite those being clinically classified as "mild" paravalvular leaks. CONCLUSIONS: Our methodology can be used to improve the thromboresistance of prosthetic valves from the initial design stage to the clinic. It allows for unparalleled optimization of devices, uncovering key TAVR leaflet design parameters that can be used to mitigate thrombogenic risk, in addition to patient-specific modeling to evaluate device performance. This work demonstrates the utility of advanced in silico analysis of TAVR devices that can be utilized for thrombogenic risk assessment of other blood recirculating devices.

Designing a Novel Asymmetric Transcatheter Aortic Valve for Stenotic Bicuspid Aortic Valves Using Patient-Specific Computational Modeling.

Bicuspid aortic valve (BAV), the most common congenital heart malformation, is characterized by the presence of only two valve leaflets with asymmetrical geometry, resulting in elliptical systolic opening. BAV often leads to early onset of calcific aortic stenosis (AS). Following the rapid expansion of transcatheter aortic valve replacement (TAVR), designed specifically for treating conventional tricuspid AS, BAV patients with AS were initially treated "off-label" with TAVR, which recently gained FDA and CE regulatory approval. Despite its increasing use in BAV, pathological BAV anatomy often leads to complications stemming from mismatched anatomical features. To mitigate these complications, a novel eccentric polymeric TAVR valve incorporating asymmetrical leaflets was designed specifically for BAV anatomies. Computational modeling was used to optimize its asymmetric leaflets for lower functional stresses and improved hemodynamic performance. Deployment and flow were simulated in patient-specific BAV models (n = 6) and compared to a current commercial TAVR valve (Evolut R 29 mm), to assess deployment and flow parameters. The novel eccentric BAV-dedicated valve demonstrated significant improvements in peak systolic orifice area, along with lower jet velocity and wall shear stress (WSS). This feasibility study demonstrates the clinical potential of the first known BAV-dedicated TAVR design, which will foster advancement of patient-dedicated valvular devices.