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.

Analysis of fibrocalcific aortic valve stenosis: computational pre-and-post TAVR haemodynamics behaviours.

Fibro-calcific aortic valve (AV) diseases are characterized by calcium growth or accumulation of fibrosis in the AV tissues. Fibrocalcific aortic stenosis (FAS) rises specifically in females, like calcification-induced aortic stenosis (CAS), may eventually necessitate valve replacement. Fluid-structure-interaction (FSI) computational models for severe CAS and FAS patients were developed using lattice Boltzmann method and multi-scale finite elements (FE). Three parametric AV models were introduced: pathology-free of non-calcified tri-and-bicuspid AVs with healthy collagen fibre network (CFN), a FAS model incorporated a thickened CFN with embedded small calcification volumes, and a CAS model employs healthy CFN with embedded high calcification volumes. The results indicate that the interaction between calcium deposits, adjacent tissue and fibres crucially influences haemodynamics and structural reactions. A fourth model of transcatheter aortic valve replacement (TAVR) post-procedure outcomes was created to study both CAS and FAS. TAVR-CAS had a higher maximum contact pressure and lower anchoring area than TAVR-FAS, making it prone to aortic tissue damage and migration. Finally, although the TAVR-CAS offered a larger opening area, its paravalvular leakage was higher. This may be attributed to a similar thrombogenicity potential characterizing both models. The computational framework emphasizes the significance of mechanobiology in FAS and underscores the requirement for tissue modelling at multiple scales.

Fluid-structure interaction modeling of compliant aortic valves using the lattice Boltzmann CFD and FEM methods.

The lattice Boltzmann method (LBM) has been increasingly used as a stand-alone CFD solver in various biomechanical applications. This study proposes a new fluid-structure interaction (FSI) co-modeling framework for the hemodynamic-structural analysis of compliant aortic valves. Toward that goal, two commercial software packages are integrated using the lattice Boltzmann (LBM) and finite element (FE) methods. The suitability of the LBM-FE hemodynamic FSI is examined in modeling healthy tricuspid and bicuspid aortic valves (TAV and BAV), respectively. In addition, a multi-scale structural approach that has been employed explicitly recognizes the heterogeneous leaflet tissues and differentiates between the collagen fiber network (CFN) embedded within the elastin matrix of the leaflets. The CFN multi-scale tissue model is inspired by monitoring the distribution of the collagen in 15 porcine leaflets. Different simulations have been examined, and structural stresses and resulting hemodynamics are analyzed. We found that LBM-FE FSI approach can produce good predictions for the flow and structural behaviors of TAV and BAV and correlates well with those reported in the literature. The multi-scale heterogeneous CFN tissue structural model enhances our understanding of the mechanical roles of the CFN and the elastin matrix behaviors. The importance of LBM-FE FSI also emerges in its ability to resolve local hemodynamic and structural behaviors. In particular, the diastolic fluctuating velocity phenomenon near the leaflets is explicitly predicted, providing vital information on the flow transient nature. The full closure of the contacting leaflets in BAV is also demonstrated. Accordingly, good structural kinematics and deformations are captured for the entire cardiac cycle.

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.

The effect of the fibrocalcific pathological process on aortic valve stenosis in female patients: a finite element study.

Calcific aortic valve disease (CAVD) is the most common heart valvular disease in the developed world. Most of the relevant research has been sex-blind, ignoring sex-related biological variables and thus under-appreciate sex differences. However, females present pronounced fibrosis for the same aortic stenosis (AS) severity compared with males, who exhibit more calcification. Herein, we present a computational model of fibrocalcific AV, aiming to investigate its effect on AS development. A parametric study was conducted to explore the influence of the total collagen fiber volume and its architecture on the aortic valve area (AVA). Towards that goal, computational models were generated for three females with stenotic AVs and different volumes of calcium. We have tested the influence of fibrosis on various parameters as fiber architecture, fibrosis location, and transvalvular pressure. We found that increased fiber volume with a low calcium volume could actively contribute to AS and reduce the AVA similarly to high calcium volume. Thus, the computed AVAs for our fibrocalcific models were 0.94 and 0.84 cm2and the clinical (Echo) AVAs were 0.82 and 0.8 cm2. For the heavily calcified model, the computed AVA was 0.8 cm2and the clinical AVA was 0.73 cm2. The proposed models demonstrated how collagen thickening influence the fibrocalcific-AS process in female patients. These models can assist in the clinical decision-making process and treatment development in valve therapy for female patients.

Structural Responses of Integrated Parametric Aortic Valve in an Electro-Mechanical Full Heart Model.

The aortic valve (AV) is located between the left ventricle and the aorta and responsible for maintaining an outward unidirectional flow. Many AV hemodynamic and structural aspects of have been extensively studied, however, more sophisticated models are needed to better understand the AV biomechanical behavior. This study deals with integrating a new parametric AV structural model with the electro-mechanical Living Heart Human Model® (LHHM). The LHHM is a finite element model simulating human heart capable of realistic electro-mechanical simulations. Different geometric metrics of AV have been examined. New integrated structural AV model within the LHHM better predict local stresses during the cardiac cycle due to the realistic boundary condition derived from the LHHM. It was found that ellipticity index (EI), calculated as the ratio between the maximal (Max) and minimal (Min) aortic annulus (AA) diameters, well correlates with measured clinical data obtained from patients undergoing computed tomography (CT) while the annular perimeter (Perim) matches the same trend. This increases the confidence in the predicted kinematic behavior, leaflets coaptation, and the overall stresses. From the clinical aspect, the new proposed coupled and integrated AV modeling can serve as a platform for design and implementation of pre-transcatheter aortic valve replacement (TAVR) procedures.

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.

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.