Transcatheter aortic valve replacement (TAVR) has emerged as an effective alternative to conventional surgical valve replacement in high-risk patients afflicted by severe aortic stenosis. Despite newer-generation devices enhancements, post-procedural complications such as paravalvular leakage (PVL) and related thromboembolic events have been hindering TAVR expansion into lower-risk patients. Computational methods can be used to build and simulate patient-specific deployment of transcatheter aortic valves (TAVs) and help predict the occurrence and degree of PVL. In this study finite element analysis and computational fluid dynamics were used to investigate the influence of procedural parameters on post-deployment hemodynamics on three retrospective clinical cases affected by PVL. Specifically, TAV implantation depth and balloon inflation volume effects on stent anchorage, degree of paravalvular regurgitation and thrombogenic potential were analyzed for cases in which Edwards SAPIEN and Medtronic CoreValve were employed. CFD results were in good agreement with corresponding echocardiography data measured in patients in terms of the PVL jets locations and overall PVL degree. Furthermore, parametric analyses demonstrated that positioning and balloon over-expansion may have a direct impact on the post-deployment TAVR performance, achieving as high as 47% in PVL volume reduction. While the model predicted very well clinical data, further validation on a larger cohort of patients is needed to verify the level of the model’s predictions in various patient-specific conditions. This study demonstrated that rigorous and realistic patient-specific numerical models could potentially serve as a valuable tool to assist physicians in pre-operative TAVR planning and TAV selection to ultimately reduce the risk of clinical complications.

Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving and effective alternative to surgical valve replacement in high-risk, elderly patients with severe calcific aortic stenosis. Despite its early promise, certain limitations and adverse events, such as suboptimal placement and valve migration, have been reported. In the present study, we aim to evaluate the effect of various TAVR deployment locations on the procedural outcome by assessing the risk for valve migration. The deployment of a balloon-expandable Edwards SAPIEN valve was simulated via finite element analysis in a patient-specific calcified aortic root, which was reconstructed from CT scans of a retrospective case of valve migration. The deployment location was parametrized in three configurations and the anchorage was quantitatively assessed based on the contact between the stent and the native valve during the deployment and recoil phases. The proximal deployment led to lower contact area between the native leaflets and the stent which poses higher risk for valve migration. The distal and midway positions resulted in comparable outcomes, with the former providing a slightly better anchorage. The approach presented might be used as a predictive tool for procedural planning in order to prevent prosthesis migration and achieve better clinical outcomes.

Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that provides an effective alternative to open-heart surgical valve replacement for treating advanced calcific aortic valve disease patients. However, complications, such as valve durability, device migration, paravalvular leakage (PVL), and thrombogenicity may lead to increased overall post-TAVR morbidity and mortality. A series of numerical studies involving a self-expandable TAVR valve were performed to evaluate these complications. Structural studies were performed with finite element (FE) analysis, followed by computational fluid dynamics (CFD) simulations, and fluidstructure interaction (FSI) analysis. The FE analysis was utilized to study the effect of TAVR valve implantation depth on valve anchorage in the Living Heart Human Model, which is capable of simulating beating heart during repeated cardiac cycles. The TAVR deployment cases where no valve migration was observed were then used to calculate the post-deployment thrombogenic potential via CFD simulations. FSI analysis followed to further assess the post-deployment TAVR hemodynamic performance for different implantation depths. The deployed valves PVL, geometric and effective orifice areas, and the leaflets structural and flow stress magnitudes were compared to determine the device optimal landing zone. The combined structural and hemodynamic analysis indicated that with the TAVR valve deployed at an aft ventricle position an optimal performance was achieved in the specific anatomy studied. Given the TAVR's rapid expansion to younger lower-risk patients, the comprehensive numerical methodology proposed here can potentially be used as a predictive tool for both procedural planning and valve design optimization to minimize the reported complications.Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1 *

Introduction: Transcatheter aortic valve replacement (TAVR) has emerged as an effective minimally-invasive alternative to surgical valve replacement in medium- to high-risk, elderly patients with calcific aortic valve disease and severe aortic stenosis. The rapid growth of the TAVR devices market has led to a high variety of designs, each aiming to address persistent complications associated with TAVR valves that may hamper the anticipated expansion of TAVR utility. Areas Covered: Here we outline the challenges and the technical demands that TAVR devices need to address for achieving the desired expansion, and review design aspects of selected, latest generation, TAVR valves of both clinically-used and investigational devices. We further review in detail some of the up-to-date modeling and testing approaches for TAVR, both computationally and experimentally, and additionally discuss those as complementary approaches to the ISO 5840–3 standard. A comprehensive survey of the prior and up-to-date literature was conducted to cover the most pertaining issues and challenges that TAVR technology faces. Expert Commentary: The expansion of TAVR over SAVR and to new indications seems more promising than ever. With new challenges to come, new TAV design approaches, and materials used, are expected to emerge, and novel testing/modeling methods to be developed.

Continuous flow ventricular assist devices (cfVADs) while effective in advanced heart failure, remain plagued by thrombosis related to abnormal flows and elevated shear stress. To limit cfVAD thrombosis, patients utilize complex anti-thrombotic regimens built upon a foundation of aspirin (ASA). While much data exists on ASA as a modulator of biochemically-mediated platelet activation, limited data exists as to the efficacy of ASA as a means of limiting shear-mediated platelet activation, particularly under elevated shear stress common within cfVADs. We investigated the ability of ASA (20, 25 and 125 μM) to limit shear-mediated platelet activation under conditions of: 1) constant shear stress (30 dyne/cm2 and 70 dyne/cm2); 2) dynamic shear stress, and 3) initial high shear exposure (70 dyne/cm2) followed by low shear exposure – i.e. a platelet sensitization protocol, utilizing a hemodynamic shearing device providing uniform shear stress in vitro. The efficacy of ASA to limit platelet activation mediated via passage through a clinical cfVAD system (DeBakey Micromed) in vitro was also studied. ASA reduced platelet activation only under conditions of low shear stress (38% reduction compared to control, n = 10, p < 0.004), with minimal protection at higher shear stress and under dynamic conditions (n = 10, p > 0.5) with no limitation of platelet sensitization. ASA had limited ability (25.6% reduction in platelet activation rate) to modulate shear-mediated platelet activation induced via cfVAD passage. These findings, while performed under “deconstructed” non-clinical conditions by utilizing purified platelets alone in vitro, provide a potential contributory mechanistic explanation for the persistent thrombosis rates experienced clinically in cfVAD patients despite ASA therapy. An opportunity exists to develop enhanced pharmacologic strategies to limit shear-mediated platelet activation at elevated shear levels associated with mechanical circulatory support devices.

Congenital bicuspid aortic valve (BAV) consists of two fused cusps and represents a major risk factor for calcific valvular stenosis. Herein, a fully coupled fluid-structure interaction (FSI) BAV model was developed from patientspecific magnetic resonance imaging (MRI) and compared against in vivo 4-dimensional flow MRI (4D Flow). FSI simulation compared well with 4D Flow, confirming direction and magnitude of the flow jet impinging onto the aortic wall as well as location and extension of secondary flows and vortices developing at systole: the systolic flow jet originating from an elliptical 1.6 cm 2 orifice reached a peak velocity of 252.2 cm/s, 0.6% lower than 4D Flow, progressively impinging on the ascending aorta convexity. The FSI model predicted a peak flow rate of 22.4 L/min, 6.7% higher than 4D Flow, and provided BAV leaflets mechanical and flowinduced shear stresses, not directly attainable from MRI. At systole, the ventricular side of the non-fused leaflet revealed the highest wall shear stress (WSS) average magnitude, up to 14.6 Pa along the free margin, with WSS progressively decreasing towards the belly. During diastole, the aortic side of the fused leaflet exhibited the highest diastolic maximum principal stress, up to 322 kPa within the attachment region. Systematic comparison with ground-truth non-invasive MRI can improve the computational model ability to reproduce native BAV hemodynamics and biomechanical response more realistically, and shed light on their role in BAV patients' risk for developing complications; this approach may further contribute to the validation of advanced FSI simulations designed to assess BAV biomechanics.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective alternative to conventional surgical aortic valve replacement (SAVR) in high-risk elderly patients with calcified aortic valve disease. All currently FDA-approved TAVR devices use tissue valves that were adapted to but not specifically designed for TAVR use. Emerging clinical evidence indicates that these valves may get damaged during crimping and deployment- leading to valvular calcification, thrombotic complications, and limited durability. This impedes the expected expansion of TAVR to lower-risk and younger patients. Viable polymeric valves have the potential to overcome such limitations. We have developed a polymeric SAVR valve, which was optimized to reduce leaflet stresses and offer a thromboresistance profile similar to that of a tissue valve. This study compares the polymeric SAVR valve's hemodynamic performance and mechanical stresses to a new version of the valve- specifically designed for TAVR. Fluid-structure interaction (FSI) models were utilized and the valves' hemodynamics, flexural stresses, strains, orifice area, and wall shear stresses were compared. The TAVR valve had 42% larger opening area and 27% higher flow rate versus the SAVR valve, while wall shear stress distribution and mechanical stress magnitudes were of the same order, demonstrating the enhanced performance of the TAVR valve prototype. The TAVR valve FSI simulation and Vivitro pulse duplicator experiments were compared in terms of the leaflets' kinematics and the effective orifice area. The numerical methodology presented can be further used as a predictive tool for valve design optimization for enhanced hemodynamics and durability.

Bicuspid aortic valve (BAV), the most common congenital valvular abnormality, generates asymmetric flow patterns and increased stresses on the leaflets that expedite valvular calcification and structural degeneration. Recently adapted for use in BAV patients, TAVR demonstrates promising performance, but post-TAVR complications tend to get exacerbated due to BAV anatomical complexities. Utilizing patient-specific computational modeling, we address some of these complications. The degree and location of post-TAVR PVL was assessed, and the risk of flow-induced thrombogenicity was analyzed in 3 BAV patients -using older generation TAVR devices that were implanted in these patients, and compared them to the performance of the newest generation TAVR devices using in silico patient models. Significant decrease in PVL and thrombogenic potential was observed after implantation of the newest generation device. The current work demonstrates the potential of using simulations in pre-procedural planning to assess post-TAVR complications, and compare the performance of different devices to achieve better clinical outcomes.