Numerical model of a valvuloplasty balloon: in vitro validation in a rapid-prototyped phantom.

BACKGROUND: Patient-specific simulations can provide insight into the mechanics of cardiovascular procedures. Amongst cardiovascular devices, non-compliant balloons are used in several minimally invasive procedures, such as balloon aortic valvuloplasty. Although these balloons are often included in the computer simulations of these procedures, validation of the balloon behaviour is often lacking. We therefore aim to create and validate a computational model of a valvuloplasty balloon. METHODS: A finite element (FE) model of a valvuloplasty balloon (Edwards 9350BC23) was designed, including balloon geometry and material properties from tensile testing. Young's Modulus and distensibility of different rapid prototyping (RP) rubber-like materials were evaluated to identify the most suitable compound to reproduce the mechanical properties of calcified arteries in which such balloons are likely to be employed clinically. A cylindrical, simplified implantation site was 3D printed using the selected material and the balloon was inflated inside it. The FE model of balloon inflation alone and its interaction with the cylinder were validated by comparison with experimental Pressure-Volume (P-V) and diameter-Volume (d-V) curves. RESULTS: Root mean square errors (RMSE) of pressure and diameter were RMSE P = 161.98 mmHg (3.8 % of the maximum pressure) and RMSE d = 0.12 mm (<0.5 mm, within the acquisition system resolution) for the balloon alone, and RMSE P = 94.87 mmHg (1.9 % of the maximum pressure) and RMSE d = 0.49 mm for the balloon inflated inside the simplified implantation site, respectively. CONCLUSIONS: This validated computational model could be used to virtually simulate more realistic valvuloplasty interventions.

A novel mono-physics particle-based approach for the simulation of cardiovascular fluid-structure interaction problems.

BACKGROUND AND OBJECTIVE: Fluid-structure interaction (FSI) is required in the study of several cardiovascular engineering problems were the mutual interaction between the pulsatile blood flow and the tissue structures is essential to establish the biomechanics of the system. Traditional FSI methods are partitioned approaches where two independent solvers, one for the fluid and one for the structure, are asynchronously coupled. This process results into high computational costs. In this work, a new FSI scheme which avoids the coupling of different solvers is presented in the framework of the truly incompressible smoothed particle hydrodynamics (ISPH) method. METHODS: In the proposed FSI method, ISPH particles contribute to define both the fluid and structural domains and are solved together in a unified system. Solid particles, geometrically defined at the beginning of the simulation, are linked through spring bounds with elastic constant providing the material Young's modulus. At each iteration, internal elastic forces are calculated to restore the springs resting length. These forces are added in the predictor step of the fractional-step procedure used to solve the momentum and continuity equations for incompressible flows of all particles. RESULTS: The method was validated with a benchmark test case consisting of a flexible beam immersed in a channel. Results showed good agreement with the system coupling approach of a well-established commercial software, ANSYS®, both in terms of fluid-dynamics and beam deformation. The approach was then applied to model a complex cardiovascular problem, consisting in the aortic valve operating function. The valve dynamics during opening and closing phases were compared qualitatively with literature results, demonstrating good consistency. CONCLUSIONS: The method is computationally more efficient than traditional FSI strategies, and overcomes some of their main drawbacks, such as the impossibility of simulating the correct valve coaptation during the closing phase. Thanks to the incompressibility scheme, the proposed FSI method is appropriate to model biological soft tissues. The simplicity and flexibility of the approach also makes it suitable to be expanded for the modelling of thromboembolic phenomena.

Left atrial appendage inversion: First computational study to shed light on the phenomenon.

Inversion of the left atrial appendage is a rare phenomenon, which may occur during the de-airing maneuvers associated to routinely performed surgery procedures, such as cardiopulmonary bypass or left ventricular assist device implantation. In this case, the body of the inverted appendage can obstruct the mitral valve leading to severe complications. The mechanisms are still poorly known, and more specific studies are needed to better understand its causes and identify mitigating strategies. The current study attempts to gain a better comprehension of the conditions and the factors favourable to left atrial appendage inversion. Four patient specific appendage morphologies, obtained from computerised tomography and representative of the main typologies commonly used for the appendage classification (chicken wing, cactus, cauliflower, and windsock), were used for the study. The numerical models were subjected to the same loading pattern, made of subsequent different pressure curves. Results show that the morphologies invert and recover their original anatomical configuration at different pressure loads, indicating that their tendency to invert is associated to their specific morphological features. Moreover, the analysis highlights that, although restoring the physiological left atrium pressure is not sufficient to induce appendage recovery, pressures well below the ventricular ones can induce the return to the natural configuration. All models recovered the anatomical configuration at pressures well below the ventricular pressure (about 100 mmHg), suggesting that basic trans-catheter maneuvers, e.g. producing temporary mitral regurgitation, could be attempted to correct the appendage configuration, prior to opt for more invasive surgical approaches.

Effect of the apron in the mechanical characterisation of hyperelastic materials by means of biaxial testing: A new method to improve accuracy.

Biological soft tissues and polymers used in biomedical applications (e.g. in the cardiovascular area) are hyperelastic incompressible materials that commonly operate under multi-axial large deformation fields. Their characterisation requires biaxial tensile testing. Due to the typically small sample size, the gripping of the specimens commonly relies on rakes or sutures, where the specimen is punctured at the edges of the gauge area. This approach necessitates of an apron, excess of material around the gauge region. This work analyses the apron influence on the estimated mechanical response of biaxial tests performed by using a rakes gripping system, with the aim of verifying the test accuracy and propose improved solutions. In order to isolate the effect of the apron, avoiding the influence of anisotropy and inhomogeneity typical of most soft tissues, homogeneous and isotropic hyperplastic samples made from a uniform sheet of casted silicone were tested. The stress-strain response of specimens with different apron sizes/shapes was measured experimentally by means of biaxial testing and digital image correlation. Tests were replicated numerically, to interpret the experimental findings. The apron surrounding the gauge area acts as an additional annular constraint which stiffens the system, resulting in a significant overestimate in the stress values. This error can be avoided by introducing specific cuts in the apron. The study quantifies, for the first time, the correlation between the apron size/shape and the experimental stress overestimation, proposing a research protocol which, although identified on homogeneous hyperelastic materials, can be useful in providing more accurate characterisation of both, synthetic polymers and soft tissues.

Fluid-structure interaction analysis of the thromboembolic risk in the left atrial appendage under atrial fibrillation: Effect of hemodynamics and morphological features.

BACKGROUND: Complications of atrial fibrillation (AF) include ischemic events originating within the left atrial appendage (LAA), a protrusion of the left atrium with variable morphological characteristics. The role of the patient specific morphology and pathological haemodynamics on the risk of ischemia remains unclear. METHODS: This work performs a comparative assessment of the hemodynamic parameters among patient-specific LAA morphologies through fluid-structure interaction computational analyses. Three LAA models per each of the four commons patient-specific morphological families (chicken wing, cactus, windsock, and cauliflower) were analysed. Mechanical properties of the tissue were based on experimental uniaxial tests on a young pig's heart. Boundary conditions were imposed based on clinical assessments of filling and emptying volumes. Sinus rhythm and atrial fibrillation operative conditions were simulated and analysed. RESULTS: For each model, the effect of morphological and functional parameters, such as the number of trabeculae and LAA stroke volume, over the hemodynamics established into the appendage was analysed. Comparison between results obtained in healthy and diseased conditions suggested the introduction of a new parameter to quantify the risk of thrombosis, here called blood stasis factor (BSF). This is defined as the LAA surface area which permanently experiences levels of shear strain rate inferior to a threshold value, set to 5 s-1 (BSF5). CONCLUSIONS: This work suggests that the current morphological classification is unsuitable to evaluate the probability of thrombus formation. However, hemodynamic parameters easy to determine from clinical examinations, such as normalised stroke volume, LAA orifice flow rate and presence of extensive trabeculations can identify departures from healthy hemodynamics in AF and support a more systematic stratification of the thromboembolic risk.

Hemodynamics in the Valsalva sinuses after transcatheter aortic valve implantation (TAVI).

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess, in vitro, the hemodynamic modifications produced by transcatheter valves in the Valsalva sinuses, by mean of phase-resolved particle image velocimetry (PIV) measurements. METHODS: Flow measurements were performed on a glass mock aortic root that included three polymeric valve leaflets, before and after the implantation of a Medtronic CoreValve device and of an Edwards SAPIEN valve. All experiments were carried out in a hydro-mechanical cardiovascular pulse duplicator system (Vivitro Superpump System SP3891) that reproduced physiologically equivalent pressures and flow rates conforming to the requirements of the standard ISO 5840:2005. The flow dynamics, before and after implantation of the two prosthetic devices, was characterized on the basis of phase-resolved velocity field and viscous shear rate measurements. RESULTS: Direct comparison indicated that both transcatheter valves determined a significant variation of flow during the early stages of valve opening and during valve closure. In general, the presence of the two valve implants significantly reduced the flow activity in the Valsalva sinuses, promoting regions of stagnation at their base. CONCLUSION: The reduction in flow in the Valsalva sinuses could be associated with the higher incidence of ischemic events reported after transcatheter heart valve implantation.

Modelling of thrombus formation using smoothed particle hydrodynamics method.

In this paper a novel model, based on the smoothed particle hydrodynamics (SPH) method, is proposed to simulate thrombus formation. This describes the main phases of the coagulative cascade through the balance of four biochemical species and three type of platelets. SPH particles can switch from fluid to solid phase when specific biochemical and physical conditions are satisfied. The interaction between blood and the forming blood clot is easily handled by an innovative monolithic FSI approach. Fluid-solid coupling is modelled by introducing elastic binds between solid particles, without requiring detention and management of the interface between the two media. The proposed model is able to realistically reproduce the thromboembolic process, as confirmed by the comparison of numerical results with experimental data available in the literature.

Compliant Aortic Annulus Sizing With Different Elliptical Ratios Through a Valvuloplasty Balloon Catheter.

OBJECTIVE: Aortic stenos (AS) is a heart valve disease that commonly affects the elderly. Transcatheter aortic valve implantation is a minimally invasive treatment that allows to replace the function of the diseased native valve with a prosthetic device, relying on catheters for device implantation. According to the current clinical guidelines, the choice of the implanted device is based on preoperative sizing determined by image-based technology. However, this assessment faces inherent limitations that can lead to sub-optimal sizing of the prosthesis; in turn, this can cause major post-operative complications like aortic regurgitation or cardiac electrical signal disruption. METHOD: By utilizing balloon pressure and volume data, this article proposes an intra-operative method for determining the dimension of the aortic annulus which takes into account its compliance and geometric irregularity. The intra-balloon pressure-volume curves were obtained using an Automated Balloon Inflation Device operating a commercially available valvuloplasty balloon catheter. A sizing algorithm to estimate the dimensions of the annulus was integrated via a validated analytical model and a numerical model for balloon free-inflation. Tests were performed on circular and elliptical idealised aortic phantoms. RESULTS: Experimental results confirm that the pressure-volume data processed with the sizing algorithm can be used to determine the circular annular diameter for all tissue rigidities. CONCLUSION: The measurement of stiffer elliptical annulus phantoms shows good accuracy and high repeatability. SIGNIFICANCE: This work represents substantial progress toward improving the selection of TAVI devices by using balloon catheters to improve the sizing of compliant aortic annuli with complex geometry.

Hydrodynamic ex vivo analysis of valve-sparing techniques: assessment and comparison.

OBJECTIVES: Valve-sparing procedures are surgical techniques allowing to restore adequate function of the native aortic valve by replacing the dysfunctional ascending aorta with a prosthetic conduit. A number of techniques are currently used, such as Yacoub's remodelling and David's reimplantation, based on a regular straight conduit. More recently, the De Paulis proposed the use of bulging conduits to reconstruct the shape of the Valsalva sinuses. This work investigates the impact of the valve-sparing technique on the aortic valve function. METHODS: The performance of 3 porcine aortic roots (Medtronic Freestyle™) was assessed in a cardiovascular pulse duplicator before and after performing 3 alternative valve-sparing procedures: David's reimplantation, Yacoub's remodelling and De Paulis' reimplantation. RESULTS: The porcine aortic roots, representative of the healthy native configuration, were characterized by the highest efficiency, with a mean energetic dissipation under normal operating conditions of 26 mJ. David's and Yacoub's techniques resulted in significantly lower performance (with mean energetic loss of about 70 mJ for both cases). The De Paulis' procedure exhibited intermediate behaviour, with superior systolic performance and valve dynamics similar to the native case, and a mean energetic loss of 38 mJ. CONCLUSIONS: The dynamics and performance after valve-sparing strongly depend on the adopted technique, with the use of conduits replicating the presence of Valsalva sinuses restoring more physiological conditions.

Valvulogenesis of a living, innervated pulmonary root induced by an acellular scaffold.

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism".

Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep.

OBJECTIVE: There is growing interest in the application of genetically engineered reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves (BHVs) to reduce antibody induced tissue calcification and accelerated structural valve degeneration (SVD). This study tested biological equivalence of valves made from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral valve implantation in sheep. METHODS: GalKO (n = 5) and standard (n = 5) porcine pericardial BHVs were implanted in a randomized and blind fashion into sheep for 90-days. Valve haemodynamic function was measured at 30-day intervals. After explantation, valves were examined for pannus, vegetation, inflammation, thrombus, and tissue calcification. RESULTS: Nine of 10 recipients completed the study. There was no difference between study groups for haemodynamic performance and no adverse valve-related events. Explanted BHVs showed mild pannus integration and minimal thrombus, with no difference between the groups. Limited focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis detected tissue calcium levels of 1.0 µg/mg ± 0.2 for GalKO BHVs and 1.9 µg/mg ± 0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. CONCLUSIONS: This is the first demonstration of biological equivalence between GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic detrimental biological nor functional impact on BHV performance. Commercial adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the clinical disparity between patients producing anti-Gal antibody and BHVs containing the Gal antigen. GalKO BHVs may reduce accelerated tissue calcification and SVD, enhancing patient choices, especially for younger patients.

Computational Analysis of Balloon Catheter Behaviour at Variable Inflation Levels.

Aortic valvuloplasty is a minimally invasive procedure for the dilatation of stenotic aortic valves. Rapid ventricular pacing is an established technique for balloon stabilization during this procedure. However, low cardiac output due to the pacing is one of the inherent risks, which is also associated with several potential complications. This paper proposes a numerical modelling approach to understand the effect of different inflation levels of a valvuloplasty balloon catheter on the positional instability caused by a pulsating blood flow. An unstretched balloon catheter model was crimped into a tri-folded configuration and inflated to several levels. Ten different inflation levels were then tested, and a Fluid-Structure Interaction model was built to solve interactions between the balloon and the blood flow modelled in an idealised aortic arch. Our computational results show that the maximum displacement of the balloon catheter increases with the inflation level, with a small step at around 50% inflation and a sharp increase after reaching 85% inflation. This work represents a substantial progress towards the use of simulations to solve the interactions between a balloon catheter and pulsating blood flow.

The Role of Patient-Specific Morphological Features of the Left Atrial Appendage on the Thromboembolic Risk Under Atrial Fibrillation.

Background: A large majority of thrombi causing ischemic complications under atrial fibrillation (AF) originate in the left atrial appendage (LAA), an anatomical structure departing from the left atrium, characterized by a large morphological variability between individuals. This work analyses the hemodynamics simulated for different patient-specific models of LAA by means of computational fluid-structure interaction studies, modeling the effect of the changes in contractility and shape resulting from AF. Methods: Three operating conditions were analyzed: sinus rhythm, acute atrial fibrillation, and chronic atrial fibrillation. These were simulated on four patient-specific LAA morphologies, each associated with one of the main morphological variants identified from the common classification: chicken wing, cactus, windsock, and cauliflower. Active contractility of the wall muscle was calibrated on the basis of clinical evaluations of the filling and emptying volumes, and boundary conditions were imposed on the fluid to replicate physiological and pathological atrial pressures, typical of the various operating conditions. Results: The LAA volume and shear strain rates were analyzed over time and space for the different models. Globally, under AF conditions, all models were well aligned in terms of shear strain rate values and predicted levels of risk. Regions of low shear rate, typically associated with a higher risk of a clot, appeared to be promoted by sudden bends and focused at the trabecule and the lobes. These become substantially more pronounced and extended with AF, especially under acute conditions. Conclusion: This work clarifies the role of active and passive contraction on the healthy hemodynamics in the LAA, analyzing the hemodynamic effect of AF that promotes clot formation. The study indicates that local LAA topological features are more directly associated with a thromboembolic risk than the global shape of the appendage, suggesting that more effective classification criteria should be identified.

Investigation of the Thermomechanical Response of Cyclically Loaded NiTi Alloys by Means of Temperature Frequency Domain Analyses.

Nickel-Titanium (NiTi) shape memory alloys subjected to cyclic loading exhibit reversible temperature changes whose modulation is correlated with the applied load. This reveals the presence of reversible thermomechanical heat sources activated by the applied stresses. One such source is the elastocaloric effect, accounting for the latent heat of Austenite-Martensite phase transformation. It is, however, observed that when the amplitude of cyclic loads is not sufficient to activate or further propagate this phase transformation, the material still exhibits a strong cyclic temperature modulation. The present work investigates the thermomechanical behaviour of NiTi under such low-amplitude cyclic loading. This is carried out by analysing the frequency domain content of temperature sampled over a time window. The amplitude and phase of the most significant harmonics are obtained and compared with the theoretical predictions from the first and second-order theories of the Thermoelastic Effect, this being the typical reversible thermomechanical coupling prevailing under elastic straining. A thin strip of NiTi, exhibiting a fully superelastic behaviour at room temperature, was investigated under low-stress amplitude tensile fatigue cycling. Full-field strain and temperature distributions were obtained by means of Digital Image Correlation and IR Thermography. The work shows that the full field maps of amplitude and phase of the first three significant temperature harmonics carry out many qualitative information about the stress and structural state of the material. It is, though, found that the second-order theory of the Thermoelastic Effect is not fully capable of justifying some of the features of the harmonic response, and further work on the specific nature of thermomechanical heat sources is required for a more quantitative interpretation.

Effect of the Alterations in Contractility and Morphology Produced by Atrial Fibrillation on the Thrombosis Potential of the Left Atrial Appendage.

Atrial fibrillation (AF) is a common arrhythmia mainly affecting the elderly population, which can lead to serious complications such as stroke, ischaemic attack and vascular dementia. These problems are caused by thrombi which mostly originate in the left atrial appendage (LAA), a small muscular sac protruding from left atrium. The abnormal heart rhythm associated with AF results in alterations in the heart muscle contractions and in some reshaping of the cardiac chambers. This study aims to verify if and how these physiological changes can establish hemodynamic conditions in the LAA promoting thrombus formation, by means of computational fluid dynamic (CFD) analyses. In particular, sinus and fibrillation contractility was replicated by applying wall velocity/motion to models based on healthy and dilated idealized shapes of the left atrium with a common LAA morphology. The models were analyzed and compared in terms of shear strain rate (SSR) and vorticity, which are hemodynamic parameters directly associated with thrombogenicity. The study clearly indicates that the alterations in contractility and morphology associated with AF pathologies play a primary role in establishing hemodynamic conditions which promote higher incidence of ischaemic events, consistently with the clinical evidence. In particular, in the analyzed models, the impairment in contractility determined a decrease in SSR of about 50%, whilst the chamber pathological dilatation contributed to a 30% reduction, indicating increased risk of clot formation. The equivalent rigid wall model was characterized by SSR values about one order of magnitude smaller than in the contractile models, and substantially different vortical behavior, suggesting that analyses based on rigid chambers, although common in the literature, are inadequate to provide realistic results on the LAA hemodynamics.

Experimental Validation of Enhanced Magnetic Resonance Imaging (EMRI) Using Particle Image Velocimetry (PIV).

Flow-sensitive four-dimensional Cardiovascular Magnetic Resonance Imaging (4D Flow CMR) has increasingly been utilised to characterise patients' blood flow, in association with patiens' state of health and disease, even though spatial and temporal resolutions still constitute a limit. Computational fluid dynamics (CFD) is a powerful tool that could expand these information and, if integrated with experimentally-obtained velocity fields, would enable to derive a large variety of the flow descriptors of interest. However, the accuracy of the flow parameters is highly influenced by the quality of the input data such as the anatomical model and boundary conditions typically derived from medical images including 4D Flow CMR. We previously proposed a novel approach in which 4D Flow CMR and CFD velocity fields are integrated to obtain an Enhanced 4D Flow CMR (EMRI), allowing to overcome the spatial-resolution limitation of 4D Flow CMR, and enable an accurate quantification of flow. In this paper, the proposed approach is validated in a U bend channel, an idealised model of the human aortic arch. The flow patterns were studied with 4D Flow CMR, CFD and EMRI, and compared with high resolution 2D PIV experiments obtained in pulsatile conditions. The main strengths and limitations of 4D Flow CMR and CFD were illustrated by exploiting the accuracy of PIV by comparing against PIV velocity fields. EMRI flow patterns showed a better qualitative and quantitative agreement with PIV results than the other techniques. EMRI enables to overcome the experimental limitations of MRI-based velocity measurements and the modelling simplifications of CFD, allowing an accurate prediction of complex flow patterns observed experimentally, while satisfying mass and momentum balance equations.

Polymeric heart valves: new materials, emerging hopes.

Heart valve (HV) replacements are among the most widely used cardiovascular devices and are in rising demand. Currently, clinically available devices are restricted to slightly modified mechanical and bioprosthetic valves. Polymeric HVs could represent an attractive alternative to the existing prostheses, merging the superior durability of mechanical valves and the enhanced haemodynamic function of bioprosthetic valves. After early unsatisfactory clinical results, polymeric HVs did not reach commercialization, mainly owing to their limited durability. Recent advances in polymers, nanomaterials and surface modification techniques together with the emergence of novel biomaterials have resulted in improved biocompatibility and biostability. Advances in HV design and fabrication methods could also lead to polymeric HVs that are suitable for long-lasting implantation. Considering all these progresses, it is likely that the new generation of polymeric HVs will find successful long-term clinical applications in future.

Percutaneous heart valve replacement: an update.

Valvular heart disease continues to be an important health care problem. Although surgical valve replacement remains the standard treatment, minimally invasive approaches for valve repair and replacement are becoming attractive alternatives among physicians and patients. In fact, percutaneous procedures can extend treatment to the increasing population of elderly patients with severe comorbidities who cannot withstand the stress of open heart surgery and to the younger patients at the early stage of valve disease, who are not treated until older ages to avoid multiple invasive surgeries. Feasibility of this technique has been shown in the first clinical experiences, and the early results are promising. However, it is clear that percutaneous valve replacement therapy is still at the early stage of development and requires enhanced implantation procedures and substantial design improvements as well as long-term follow-up to show the safety and effectiveness of this new treatment modality.

Does transcatheter aortic valve alignment matter?

Objective: This study investigates the effect of transcatheter aortic valve (TAV) angular alignment on the postprocedure haemodynamics. TAV implantation has emerged as an effective alternative to surgery when treating valve dysfunction. However, the benefit of avoiding surgery is paid back by the inability to remove the native diseased leaflets and accurately position the device in relation to the aortic root, and the literature has shown the root anatomy and substitute position can play an essential role on valve function. Methods: A commercial TAV was placed in a silicone mock aortic root in vitro, including mock native leaflets, and either aligned commissure-to-commissure or in maximum misalignment. Haemodynamic performance data at various stroke volumes were measured, and Particle Image Velocimetry analysis was performed at a typical stroke volume for rest conditions. The two configurations were also studied without mock native leaflets, for comparison with previous in vitro studies. Results: Haemodynamic performance data were similar for all configurations. However, imaging analysis indicated that valve misalignment resulted in the central jet flow not extending to the root wall in the native commissures' vicinity, replaced by a low shear flow, and a reduction of upper sinus flow of 40%, increasing flow stagnation in the sinus. Conclusions: TAV misalignment did not result in a significant change in valve hydrodynamic performance, but determined some change in the fluid flow patterns, which may promote pathological scenarios, such as increased thrombogenicity of blood flow within the sinuses of Valsalva, and plaque formation around the lumen of the sinotubular junction.