Fragmentation of Different Calcification Growth Patterns in Bicuspid Valves During Balloon Valvuloplasty Procedure.

This study focuses on the calcification development and routes of type-1 bicuspid aortic valves based on CT scans and the effect of the unique geometrical shapes of calcium deposits on their fragmentation under balloon valvuloplasty procedures. Towards this goal, the novel Reverse Calcification Technique (RCT), which can predict the calcification progression leading to the current state based on CT scans, is utilized for n = 26 bicuspid aortic valves patients. Two main calcification patterns of type-1 bicuspid aortic valves were identified; asymmetric and symmetric with either partial or full arcs and circles. Subsequently, a calcification fragmentation biomechanical model was introduced to study the balloon valvuloplasty procedure prior to transcatheter aortic valve replacement implantation that allows better device expansion. To achieve this goal, six representative stenotic bicuspid aortic valves of different calcification patterns were investigated. It was found that the distinct geometrical shape of the calcium deposits had a significant effect on the cracks' initiations. Full or partial circle deposits had stronger resistance to fragmentation and mainly remained intact, yet, arc-shaped pattern deposits resulted in multiple cracks in bottleneck regions. The proposed biomechanical computational models could help assess calcification fragmentation patterns toward improving treatment approaches in stenotic bicuspid aortic valve patients, particularly for the off-label use of transcatheter aortic valve replacement.

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 3.85 m s-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.

Biomechanical modeling of transcatheter aortic valve replacement in a stenotic bicuspid aortic valve: deployments and paravalvular leakage.

Calcific aortic valve disease (CAVD) is characterized by stiffened aortic valve leaflets. Bicuspid aortic valve (BAV) is the most common congenital heart disease. Transcatheter aortic valve replacement (TAVR) is a treatment approach for CAVD where a stent with mounted bioprosthetic valve is deployed on the stenotic valve. Performing TAVR in calcified BAV patients may be associated with post-procedural complications due to the BAV asymmetrical structure. This study aims to develop refined computational models simulating the deployments of Evolut R and PRO TAVR devices in a representative calcified BAV. The paravalvular leakage (PVL) was also calculated by computational fluid dynamics simulations. Computed tomography scan of severely stenotic BAV patient was acquired. The 3D calcium deposits were generated and embedded inside a parametric model of the BAV. Deployments of the Evolut R and PRO inside the calcified BAV were simulated in five bioprosthesis leaflet orientations. The hypothesis of asymmetric and elliptic stent deployment was confirmed. Positioning the bioprosthesis commissures aligned with the native commissures yielded the lowest PVL (15.7 vs. 29.5 mL/beat). The Evolut PRO reduced the PVL in half compared with the Evolut R (15.7 vs. 28.7 mL/beat). The proposed biomechanical computational model could optimize future TAVR treatment in BAV patients. Graphical abstract.

A New Growth Model for Aortic Valve Calcification.

Calcific aortic valve disease (CAVD) is a progressive disease in which minerals accumulate in the tissue of the aortic valve cusps, stiffening them and preventing valve opening and closing. The process of valve calcification was found to be similar to that of bone formation including cell differentiation to osteoblast-like cells. Studies have shown the contribution of high strains to calcification initiation and growth process acceleration. In this paper, a new strain-based calcification growth model is proposed. The model aims to explain the unique shape of the calcification and other disease characteristics. The calcification process was divided into two stages: Calcification initiation and calcification growth. The initiation locations were based on previously published findings and a reverse calcification technique (RCT), which uses computed tomography (CT) scans of patients to reveal the calcification initiation point. The calcification growth process was simulated by a finite element model of one aortic valve cusp loaded with cyclic loading. Similar to Wolff's law, describing bone response to stress, our model uses strains to drive calcification formation. The simulation grows calcification from its initiation point to its full typical stenotic shape. Study results showed that the model was able to reproduce the typical calcification growth pattern and shape, suggesting that strain is the main driving force behind calcification progression. The simulation also sheds light on other disease characteristics, such as calcification growth acceleration as the disease progresses, as well as sensitivity to hypertension.

Fluid-Structure Interaction Models of Bicuspid Aortic Valves: The Effects of Nonfused Cusp Angles.

Bicuspid aortic valve (BAV) is the most common type of congenital heart disease, occurring in 0.5-2% of the population, where the valve has only two rather than the three normal cusps. Valvular pathologies, such as aortic regurgitation and aortic stenosis, are associated with BAVs, thereby increasing the need for a better understanding of BAV kinematics and geometrical characteristics. The aim of this study is to investigate the influence of the nonfused cusp (NFC) angle in BAV type-1 configuration on the valve's structural and hemodynamic performance. Toward that goal, a parametric fluid-structure interaction (FSI) modeling approach of BAVs is presented. Four FSI models were generated with varying NFC angles between 120 deg and 180 deg. The FSI simulations were based on fully coupled structural and fluid dynamic solvers and corresponded to physiologic values, including the anisotropic hyper-elastic behavior of the tissue. The simulated angles led to different mechanical behavior, such as eccentric jet flow direction with a wider opening shape that was found for the smaller NFC angles, while a narrower opening orifice followed by increased jet flow velocity was observed for the larger NFC angles. Smaller NFC angles led to higher concentrated flow shear stress (FSS) on the NFC during peak systole, while higher maximal principal stresses were found in the raphe region during diastole. The proposed biomechanical models could explain the early failure of BAVs with decreased NFC angles, and suggests that a larger NFC angle is preferable in suture annuloplasty BAV repair surgery.

Fluid-structure interaction modeling of calcific aortic valve disease using patient-specific three-dimensional calcification scans.

Calcific aortic valve disease (CAVD) is characterized by calcification accumulation and thickening of the aortic valve cusps, leading to stenosis. The importance of fluid flow shear stress in the initiation and regulation of CAVD progression is well known and has been studied recently using fluid-structure interaction (FSI) models. While cusp calcifications are three-dimensional (3D) masses, previously published FSI models have represented them as either stiffened or thickened two-dimensional (2D) cusps. This study investigates the hemodynamic effect of these calcifications employing FSI models using 3D patient-specific calcification masses. A new reverse calcification technique (RCT) is used for modeling different stages of calcification growth based on the spatial distribution of calcification density. The RCT is applied to generate the 3D calcification deposits reconstructed from a patient-specific CT scans. Our results showed that consideration of 3D calcification deposits led to both higher fluid shear stresses and unique fluid shear stress distribution on the aortic side of the cusps that may have an impact on the calcification growth rate. However, the flow did not seem to affect the geometry of the calcification during the growth phase.

Imaging analysis of collagen fiber networks in cusps of porcine aortic valves: effect of their local distribution and alignment on valve functionality.

The cusps of native aortic valve (AV) are composed of collagen bundles embedded in soft tissue, creating a heterogenic tissue with asymmetric alignment in each cusp. This study compares native collagen fiber networks (CFNs) with a goal to better understand their influence on stress distribution and valve kinematics. Images of CFNs from five porcine tricuspid AVs are analyzed and fluid-structure interaction models are generated based on them. Although the valves had similar overall kinematics, the CFNs had distinctive influence on local mechanics. The regions with dilute CFN are more prone to damage since they are subjected to higher stress magnitudes.

Progressive aortic valve calcification: three-dimensional visualization and biomechanical analysis.

Calcific aortic valve disease (CAVD) is a progressive pathology characterized by calcification mainly within the cusps of the aortic valve (AV). As CAVD advances, the blood flow and associated hemodynamics are severely altered, thus influencing the mechanical performance of the AV. This study proposes a new method, termed reverse calcification technique (RCT) capable of re-creating the different calcification growth stages. The RCT is based on three-dimensional (3D) spatial computed tomography (CT) distributions of the calcification density from patient-specific scans. By repeatedly subtracting the calcification voxels with the lowest Hounsfield unit (HU), only high calcification density volume is presented. RCT posits that this volume re-creation represents earlier calcification stages and may help identify CAVD initiation sites. The technique has been applied to scans from 12 patients (36 cusps) with severe aortic stenosis who underwent CT before transcatheter aortic valve implantation (TAVI). Four typical calcification geometries and growth patterns were identified. Finite elements (FE) analysis was applied to compare healthy AV structural response with two selected CAVD-RCT configurations. The orifice area decreased from 2.9cm(2) for the healthy valve to 1.4cm(2) for the moderate stenosis case. Local maximum strain magnitude of 0.24 was found on the edges of the calcification compared to 0.17 in the healthy AV, suggesting a direct relation between strain concentration and calcification geometries. The RCT may help predict CAVD progression in patients at early stages of the disease. The RCT allows a realistic FE mechanical simulation and performance of calcified AVs.

Fluid-structure interaction model of aortic valve with porcine-specific collagen fiber alignment in the cusps.

Native aortic valve cusps are composed of collagen fibers embedded in their layers. Each valve cusp has its own distinctive fiber alignment with varying orientations and sizes of its fiber bundles. However, prior mechanical behavior models have not been able to account for the valve-specific collagen fiber networks (CFN) or for their differences between the cusps. This study investigates the influence of this asymmetry on the hemodynamics by employing two fully coupled fluid-structure interaction (FSI) models, one with asymmetric-mapped CFN from measurements of porcine valve and the other with simplified-symmetric CFN. The FSI models are based on coupled structural and fluid dynamic solvers. The partitioned solver has nonconformal meshes and the flow is modeled by employing the Eulerian approach. The collagen in the CFNs, the surrounding elastin matrix, and the aortic sinus tissues have hyperelastic mechanical behavior. The coaptation is modeled with a master-slave contact algorithm. A full cardiac cycle is simulated by imposing the same physiological blood pressure at the upstream and downstream boundaries for both models. The mapped case showed highly asymmetric valve kinematics and hemodynamics even though there were only small differences between the opening areas and cardiac outputs of the two cases. The regions with a less dense fiber network are more prone to damage since they are subjected to higher principal stress in the tissues and a higher level of flow shear stress. This asymmetric flow leeward of the valve might damage not only the valve itself but also the ascending aorta.

Numerical model of the aortic root and valve: optimization of graft size and sinotubular junction to annulus ratio.

OBJECTIVE: The aim of this study was to determine the influence of aortic annulus (AA) diameter and the ratio of the sinotubular junction (STJ) diameter to the AA diameter on aortic valve hemodynamics and tissue mechanics and to suggest optimal values. METHODS: Sixteen cases of aortic roots with AA diameters between 22 and 28 mm and an STJ/AA diameter ratio between 0.8 and 1.4 were numerically modeled. Average coaptation height and mechanical stresses were calculated from 3-dimensional finite element analysis of the aortic valve and root. Five additional fluid structure interaction (FSI) models with an AA diameter of 24 mm and an STJ/AA ratio between 0.6 and 1.4 were also constructed. The material properties of the tissues were from porcine valves and boundary conditions were physiologic and normal blood pressures. RESULTS: In most cases, average coaptation height decreased with an increase in the STJ/AA ratio. Those cases with AA diameters between 24 and 26 mm and an STJ/AA ratio between 0.8 and 1.0 had a relatively large average coaptation height (>3 mm) and similar stress distribution during diastole. The flow shear stress values on the cusps at peak systole increased at the same time as the STJ/AA ratio decreased, similar to the opening area. CONCLUSIONS: Relatively large coaptation, low stress in the tissues during diastole, and low flow shear stress during systole is the best combination for cases of AA diameter between 24 and 26 mm with identical STJ diameter. Valve-sparing procedures that prevent AA expansion are preferable.