Validating In Silico and In Vitro Patient-Specific Structural and Flow Models with Transcatheter Bicuspid Aortic Valve Replacement Procedure.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which had been treated off-label by transcatheter aortic valve replacement (TAVR) procedure for several years, until its recent approval by the Food and Drug Administration (FDA) and Conformité Européenne (CE) to treat BAVs. Post-TAVR complications tend to get exacerbated in BAV patients due to their inherent aortic root pathologies. Globally, due to the paucity of randomized clinical trials, clinicians still favor surgical AVR as the primary treatment option for BAV patients. While this warrants longer term studies of TAVR outcomes in BAV patient cohorts, in vitro experiments and in silico computational modeling can be used to guide the surgical community in assessing the feasibility of TAVR in BAV patients. Our goal is to combine these techniques in order to create a modeling framework for optimizing pre-procedural planning and minimize post-procedural complications. MATERIALS AND METHODS: Patient-specific in silico models and 3D printed replicas of 3 BAV patients with different degrees of post-TAVR paravalvular leakage (PVL) were created. Patient-specific TAVR device deployment was modeled in silico and in vitro-following the clinical procedures performed in these patients. Computational fluid dynamics simulations and in vitro flow studies were performed in order to obtain the degrees of PVL in these models. RESULTS: PVL degree and locations were consistent with the clinical data. Cross-validation comparing the stent deformation and the flow parameters between the in silico and the in vitro models demonstrated good agreement. CONCLUSION: The current framework illustrates the potential of using simulations and 3D printed models for pre-TAVR planning and assessing post-TAVR complications in BAV patients.

Assessment of Paravalvular Leak Severity and Thrombogenic Potential in Transcatheter Bicuspid Aortic Valve Replacements Using Patient-Specific Computational Modeling.

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. Patient-specific computational framework to assess post-transcatheter bicuspid aortic valve replacement paravalvular leakage and flow-induced thrombogenic complications and compare device performances.

Patient-Specific Bicuspid Aortic Valve Biomechanics: A Magnetic Resonance Imaging Integrated Fluid-Structure Interaction Approach.

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 patient-specific 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 cm2 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 flow-induced 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.

Numerical evaluation of transcatheter aortic valve performance during heart beating and its post-deployment fluid-structure interaction analysis.

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 fluid-structure 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.

Correction to: Patient-specific simulation of transcatheter aortic valve replacement: impact of deployment options on paravalvular leakage.

This is to inform that the original article was published without the "Conflict of Interest" statement.

Patient-specific simulation of transcatheter aortic valve replacement: impact of deployment options on paravalvular leakage.

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.

Principles of TAVR valve design, modelling, and testing.

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.

Effect of Balloon-Expandable Transcatheter Aortic Valve Replacement Positioning: A Patient-Specific Numerical Model.

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, it was aimed 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.

Simulation of Transcatheter Aortic Valve Replacement in patient-specific aortic roots: Effect of crimping and positioning on device performance.

Calcific aortic valve disease (CAVD) is a cardiovascular condition that causes the progressive narrowing of the aortic valve (AV) opening, due to the growth of bone-like deposits all over the aortic root (AR). Transcatheter aortic valve replacement (TAVR), a minimally invasive procedure, has recently become the only lifesaving solution for patients that cannot tolerate the standard surgical valve replacement. However, adverse effects, such as AR injury or paravalvular leakage (PVL), may occur as a consequence of a sub-optimal procedure, due to the presence of calcifications in situ. Additionally, the crimping required for delivering the valve via stenting may damage the valve. The aim of the present study is to comparatively assess the crimping mechanics of the commercialized Edwards SAPIEN valve and an alternative polymeric valve (Polynova, Inc) and to evaluate the effect of different TAVR deployment positions using patient-specific numerical models. The optimal deployment location for achieving better patient outcomes was calculated and based on the interactions between the TAVR stent and the native AR. Results demonstrated that the Polynova valve withstands the crimping process better than the SAPIEN valve. Furthermore, deployment simulations showed the role that calcifications deposits may play in the TAVR sub-optimal valve anchoring to the AV wall, leading to the presence of gaps that result in PVL.