Bicuspid Aortic Valve Model Research Articles

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 29mm), 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.

A computational analysis of potential aortic dilation induced by the hemodynamic effects of bicuspid aortic valve phenotypes

Background and objectivesThe bicuspid aortic valve (BAV) is a major risk factor for the progression of aortic dilation (AD) because of the induced abnormal blood flow environment in aorta. The differences in the development of AD induced by BAV phenotypes remains unclear. Therefore, the objective of this study was to assess the potential locations of AD induced by different phenotypes of BAV. The different effects of opening orifice area and leaflet orientation on ascending aortic hemodynamics in Type-1 BAV was investigated by means of numerical simulation. MethodsFinite element dynamic analysis was performed on tricuspid aortic valve (TAV) and BAV models to simulate the motion of the leaflets and obtain the geometrical characteristics of AV at peak systole as a reference, which were used for aortic models. Then, four sets of aortic fluid models were designed according to the leaflet fusion types [TAV; BAV (left-right-coronary cusp fusion, LR; right-non-coronary cusp fusion, RN; left-non-coronary cusp fusion, LN)], and the computational fluid dynamics method was applied to compare the hemodynamic differences within the aorta at peak systole. ResultsThe maximum opening area of BAV was significantly reduced, resulting in alterations in aortic hemodynamics compared with TAV. The velocity streamlines were essentially parallel to the aortic wall in TAV. The average pressure and wall shear stress in aorta tend to be stable. In contrary, the eccentricity of BAV orifice jet resulted in high-velocity flow directed toward the ascending aorta (AA) wall and aortic arch for LR and LN; RN features an asymmetrical velocity distribution toward the outer bend of the middle AA, and eccentric flow tends to impact the distal AA. As the flow angle is associated with distinct flow impingement locations, different degrees of WSS and pressure concentration occur along the aortic wall from the AA to the aortic arch in three BAV types. ConclusionsThe BAV morphotype affects the aortic hemodynamics, and the abnormal blood flow associated with BAV may play a role in AD. The different BAV phenotypes determine the direction of blood flow jet and change the expression of dilation. LR is likely to cause dilation of the tubular AA; RN results in dilation of the middle AA to proximal aortic arch; and LN causes an increased incidence of the tubular AA and the proximal aortic arch.

Abstract 9587: Combined Aortic Regurgitation and Stenosis of the Bicuspid Aortic Valve Increases Ascending Aortic Wall Shear Stress and Left Ventricle Energy Burden

Introduction: The bicuspid aortic valve (BAV) opening pattern and the degree of aortic stenosis (AS) are reportedly associated with the aneurysmal formation in the ascending aorta. Although AS is often accompanied by aortic regurgitation (AR), the combined effect of AR and AS on the wall of the ascending aorta and energy loss of the blood flow are not well understood. Hypothesis: We hypothesize that AR along with AS can increase the wall shear stress (WSS) to develop the aneurysm in the ascending aorta and increase the load on the left ventricle (LV). Methods: The effects of AR along with AS BAV on the hemodynamic features were assessed using an image-based subject-specific LV-aorta integrated computational model. The computational model was constructed based on an MRI dataset of a 72-year-old healthy volunteer. Four different types of stenosed (52% stenosis) BAV models were created: Type 0, RL fused, RN fused, and LN fused. Then, physiological boundary conditions were given based on a parameter-adjusted 0-1D cardiovascular model of the AS BAV with no AR, mild AR (17% regurgitant fraction (RF)), and severe AR (48% RF) to assess hemodynamic indices such as time-average of WSS in the ascending aorta and pulsatile energy loss index (PELI), an index to estimate energy loss in the aorta. Results: Averaged WSS was highest in the severe AR with AS BAV in 4.1±0.2 Pa, followed by the mild AR with AS BAV in 3.1±0.21 Pa, and no AR with AS BAV in 2.7±0.3 Pa. The intra-ventricular flow (LV) showed more disturbed flow in mid-diastole in severe AR with AS BAV. PELI was augmented in mild AR with AS BAV in 0.34±0.05 and severe AR with AS BAV in 0.25±0.06, compared to no AR with AS BAV in 0.19±0.16. Conclusions: AR along with AS in BAV has a great impact on increasing the WSS in the ascending aorta and increasing the energy loss of the flow in the aorta. These features imply that advanced AR along with AS in BAV may raise the risk of the development of aortic aneurysm as well as heart failure due to the increased workload on the LV.

Abstract 12817: Experimental Analysis of Bicuspid Aortic Valve Hemodynamics: Effect of Mild Aortic Dilatation on Systolic Flow Characteristics

Introduction: Aortic diameter is a determinant index in deciding surgical intervention for aortic aneurysm with bicuspid aortic valve (BAV). However, the treatment of a mildly dilated ascending aorta remains controversial. We experimentally investigated influence of mild dilatation of the ascending aorta on BAV-related hemodynamics in 3 BAV morphologies. Methods: An MRI-compatible pulsatile flow circulation system incorporating an aortic valve model and aortic arch model was developed. Tricuspid aortic valve (TAV) and 3 asymmetric BAV models including RL-, RN-, and LN-BAV were constructed by suturing bovine pericardium as cusps to aorta. The aortic arch models with the ascending diameters of 30 mm (non-dilatation) and 40 mm (mildly dilatation) were compared. Streamlines and the circulations (m 2 /s) of peak systolic flow in non- and mildly dilated ascending aorta were assessed using 4D-flow MRI in each BAV morphology (Fig). Results: Streamlines showed eccentric aortic valvular outflow jets impinging on the outer curvature of the ascending aorta, proximal arch, and left-anterior supra-valvular aortic wall in RL-, RN-, and LN-BAV, respectively. Regardless of the non-dilated or mildly dilated aorta, the circulations of peak systolic flow were larger in the BAVs than the TAV model (non-dilated aorta, TAV 0.005; RL- 0.016; RN- 0.026; LN-BAV 0.011 m 2 /s, mildly dilated aorta, TAV 0.009; RL- 0.017; RN- 0.028; LN-BAV 0.025 m 2 /s). Right-handed rotation was observed in RL- and RN-BAV, whereas LN-BAV presented left-handed rotation. In LN-BAV, the circulation markedly increased in the mildly dilated ascending aorta. Conclusions: Asymmetric BAV morphology was associated with highly eccentric aortic valvular outflow jet that directly impinged on the aortic wall, and the large circulation of peak systolic flow. The dilatation of the ascending aorta, even mild dilatation, might induce further increase in the circulation of systolic flow, especially in LN-BAV morphology.

Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85ms-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.

Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.

A bicuspid aortic valve (BAV) is the most common cardiac malformation, found in 0.5% to 2% of the population. BAVs are present in approximately 50% of patients with severe aortic stenosis and are an independent risk factor for aortic aneurysms. Currently, there are no therapeutics to treat BAV, and the human mutations identified to date represent a relatively small number of BAV patients. However, the discovery of BAV in an increasing number of genetically modified mice is advancing our understanding of molecular pathways that contribute to BAV formation. In this study, we utilized the comparison of BAV phenotypic characteristics between murine models as a tool to advance our understanding of BAV formation. The collation of murine BAV data indicated that excess versican within the provisional extracellular matrix (P-ECM) is a common factor in BAV development. While the percentage of BAVs is low in many of the murine BAV models, the remaining mutant mice exhibit larger and more amorphous tricuspid AoVs, also with excess P-ECM compared to littermates. The identification of common molecular characteristics among murine BAV models may lead to BAV therapeutic targets and biomarkers of disease progression for this highly prevalent and heterogeneous cardiovascular malformation.

A Fluid-Structure Interaction Study of Different Bicuspid Aortic Valve Phenotypes Throughout the Cardiac Cycle.

The bicuspid aortic valve (BAV) is a congenital malformation of the aortic valve with a variety of structural features. The current research on BAV mainly focuses on the systolic phase, while ignoring the diastolic hemodynamic characteristics and valve mechanics. The purpose of this study is to compare the differences in hemodynamics and mechanical properties of BAV with different phenotypes throughout the cardiac cycle by means of numerical simulation. Based on physiological anatomy, we established an idealized tricuspid aortic valve (TAV) model and six phenotypes of BAV models (including Type 0 a–p, Type 0 lat, Type 1 L–R, Type 1 N-L, Type 1 R-N, and Type 2), and simulated the dynamic changes of the aortic valve during the cardiac cycle using the fluid–structure interaction method. The morphology of the leaflets, hemodynamic parameters, flow patterns, and strain were analyzed. Compared with TAV, the cardiac output and effective orifice area of different BAV phenotypes decreased certain degree, along with the peak velocity and mean pressure difference increased both. Among all BAV models, Type 2 exhibited the worst hemodynamic performance. During the systole, obvious asymmetric flow field was observed in BAV aorta, which was related to the orientation of BAV. Higher strain was generated in diastole for BAV models. The findings of this study suggests specific differences in the hemodynamic characteristics and valve mechanics of different BAV phenotypes, including different severity of stenosis, flow patterns, and leaflet strain, which may be critical for prediction of other subsequent aortic diseases and differential treatment strategy for certain BAV phenotype.

The efficacy of sinus plication in aortic valvuloplasty for bicuspid aortic valve: experiments in a pulsatile flow simulation model.

Sinus plication has emerged as a promising tool that can lead to better stability in bicuspid aortic valve (BAV) repair. However, the mechanisms underlying the efficacy of this technique are unclear. We evaluated the hydrodynamic effect of sinus plication using the experimental pulsatile flow simulator and our original BAV model in vitro. Based on the computed tomography data of a BAV patient who had undergone aortic valvuloplasty, a BAV model (group C, n = 6) was developed with bovine pericardium and vascular prosthesis (J-graft Shield Neo Valsalva 24 mm). We performed sinus plication (group SP, n = 6) in the BAV model and compared hydrodynamic data with the control model in the pulsatile flow simulator. Non-fused cusp angle, annulus diameter and effective height were measured by ultrasonography. The average flow was significantly increased in group SP compared to group C (4.24 ± 0.14 l/min vs 4.14 ± 0.15 l/min, respectively, P = 0.034). The mean transvalvular pressure gradient and regurgitant fraction were significantly decreased in group SP compared to group C (11.6 ± 4.3 mmHg vs 16.6 ± 5.0 mmHg, respectively, P = 0.009 and 14.1 ± 2.0% vs 17.4 ± 2.1%, respectively, P = 0.001). Ultrasound measurement indicated that non-fused cusp angle was significantly increased in group SP compared to group C (163.8° ± 9.2° vs 153.0° ± 4.6°, respectively, P = 0.012). Sinus plication in the BAV model significantly increased the commissural angle. It was effective in not only controlling regurgitation but also improving valve opening. These finding should be confirmed by evaluating cusp stress and/or long-term durability in the future studies.

Abstract 14618: Bicuspid Aortic Valve Morphology and Risk Factors of Abnormal Hemodynamics: An Experimental Investigation of Velocity, Vorticity and Eccentricity of Systolic Jet Stream, Using a Magnetic Resonance Imaging Compatible Pulsatile Flow Circulation System

Introduction: Abnormal hemodynamics with bicuspid aortic valve (BAV) is influenced by the BAV morphology. However, due to the morphological variety, the relationship between BAV morphology and hemodynamics has not been well clarified. We experimentally investigated influences of BAV morphology on hemodynamics. Methods: An MRI compatible pulsatile flow circulation system incorporating an aortic valve model and morphologically relevant aortic arch model was developed. Two types of BAV models with cusp angles of 240-120 (asymmetric BAV) and 180-180 (symmetric BAV) were prepared using bovine aorta and pericardium. The vorticity and eccentricity of jet in the aortic arch model in systolic phase were assessed using 4D-flow MRI. Streamlines at peak systole were compared among 5 BAV morphologies defined based on the symmetry and the position of leaflets (Fig). Results: Eccentric supra-valvular jets directed to the aortic wall faced to the smaller leaflet were present in the 3 asymmetric BAVs. In the ABAV-1, a markedly eccentric jet impinging on the aortic outer curvature was present. In the ABAV-2, a left-posterior directed jet shifting to the outer curvature of proximal arch was present. The asymmetric BAVs induced larger flow vorticity in the ascending aorta than the symmetric BAVs (ABAV-1 vs -2 vs -3 vs SBAV-1 vs -2, 0.018 vs 0.019 vs 0.014 vs 0.010 vs 0.011 m 2 /s). The ABAV-2 had a larger vortex in the middle arch than the ABAV-1 (ABAV-2 vs -1, 0.010 vs 0.005 m 2 /s). Conclusion: Our study indicated that the angles and orientations of the BAV impacted on the locations of jets impinging on the aortic wall and magnitudes of vorticities in systole. In the asymmetric BAVs, the direction of jet was influenced by the position of smaller leaflet. Our data suggests that the ABAV-1 morphology may be a risk factor inducing asymmetric aneurysm bulged toward the aortic outer curvature, while the ABAV-2 morphology may be a risk factor of an aortic aneurysm involving the transvers arch.

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.

Steady Flow Hemodynamic and Energy Loss Measurements in Normal and Simulated Calcified Tricuspid and Bicuspid Aortic Valves

The bicuspid aortic valve (BAV), which forms with two leaflets instead of three as in the normal tricuspid aortic valve (TAV), is associated with a spectrum of secondary valvulopathies and aortopathies potentially triggered by hemodynamic abnormalities. While studies have demonstrated an intrinsic degree of stenosis and the existence of a skewed orifice jet in the BAV, the impact of those abnormalities on BAV hemodynamic performance and energy loss has not been examined. This steady-flow study presents the comparative in vitro assessment of the flow field and energy loss in a TAV and type-I BAV under normal and simulated calcified states. Particle-image velocimetry (PIV) measurements were performed to quantify velocity, vorticity, viscous, and Reynolds shear stress fields in normal and simulated calcified porcine TAV and BAV models at six flow rates spanning the systolic phase. The BAV model was created by suturing the two coronary leaflets of a porcine TAV. Calcification was simulated via deposition of glue beads in the base of the leaflets. Valvular performance was characterized in terms of geometric orifice area (GOA), pressure drop, effective orifice area (EOA), energy loss (EL), and energy loss index (ELI). The BAV generated an elliptical orifice and a jet skewed toward the noncoronary leaflet. In contrast, the TAV featured a circular orifice and a jet aligned along the valve long axis. While the BAV exhibited an intrinsic degree of stenosis (18% increase in maximum jet velocity and 7% decrease in EOA relative to the TAV at the maximum flow rate), it generated only a 3% increase in EL and its average ELI (2.10 cm2/m2) remained above the clinical threshold characterizing severe aortic stenosis. The presence of simulated calcific lesions normalized the alignment of the BAV jet and resulted in the loss of jet axisymmetry in the TAV. It also amplified the degree of stenosis in the TAV and BAV, as indicated by the 342% and 404% increase in EL, 70% and 51% reduction in ELI and 48% and 51% decrease in EOA, respectively, relative to the nontreated valve models at the maximum flow rate. This study indicates the ability of the BAV to function as a TAV despite its intrinsic degree of stenosis and suggests the weak dependence of pressure drop on orifice area in calcified valves.

Fully coupled fluid–structure interaction model of congenital bicuspid aortic valves: effect of asymmetry on hemodynamics

A bicuspid aortic valve (BAV) is a congenital cardiac disorder where the valve consists of only two cusps instead of three, as in a normal tricuspid valve (TAV). Although 97% of BAVs include asymmetric cusps, little or no prior studies have investigated the blood flow through a three-dimensional BAV and root. The aim of the present study was to characterize the effect of asymmetric BAV on the blood flow using fully coupled fluid-structure interaction (FSI) models with improved boundary conditions and tissue properties. This study presents four FSI models, including a native TAV, asymmetric BAVs with or without a raphe, and an almost symmetric BAV. Cusp tissue is composed of hyperelastic finite elements with collagen fibres embedded in the elastin matrix. A full cardiac cycle is simulated by imposing the same physiological blood pressures for all the TAV and BAV models. The latter have significantly smaller opening areas compared with the TAV. Larger stress values were found in the cusps of BAVs with fused cusps, at both the systolic and diastolic phases. The asymmetric geometry caused asymmetric vortices and much larger flow shear stress on the cusps which could be a potential initiator for early valvular calcification of BAVs.

The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

In Vitro Characterization of Bicuspid Aortic Valve Hemodynamics Using Particle Image Velocimetry

The congenital bicuspid aortic valve (BAV) is associated with increased leaflet calcification, ascending aortic dilatation, aortic stenosis (AS) and regurgitation (AR). Although underlying genetic factors have been primarily implicated for these complications, the altered mechanical environment of BAVs could potentially accelerate these pathologies. The objective of the current study is to characterize BAV hemodynamics in an in vitro system. Two BAV models of varying stenosis and jet eccentricity and a trileaflet AV (TAV) were constructed from excised porcine AVs. Particle Image Velocimetry (PIV) experiments were conducted at physiological flow and pressure conditions to characterize fluid velocity fields in the aorta and sinus regions, and ensemble averaged Reynolds shear stress and 2D turbulent kinetic energy were calculated for all models. The dynamics of the BAV and TAV models matched the characteristics of these valves which are observed clinically. The eccentric and stenotic BAV showed the strongest systolic jet (V = 4.2 m/s), which impinged on the aortic wall on the non-fused leaflet side, causing a strong vortex in the non-fused leaflet sinus. The magnitudes of TKE and Reynolds stresses in both BAV models were almost twice as large as comparable values for TAV, and these maximum values were primarily concentrated around the central jet through the valve orifice. The in vitro model described here enables detailed characterization of BAV flow characteristics, which is currently challenging in clinical practice. This model can prove to be useful in studying the effects of altered BAV geometry on fluid dynamics in the valve and ascending aorta. These altered flows can be potentially linked to increased calcific responses from the valve endothelium in stenotic and eccentric BAVs, independent of concomitant genetic factors.