On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part II: Spectral analysis and anisotropy.

Severe aortic valve stenosis can lead to heart failure and aortic valve replacement (AVR) is the primary treatment. However, increasing prevalence of aortic stenosis cases reveal limitations in current replacement options, necessitating improved prosthetic aortic valves. We investigate flow disturbances downstream of severe aortic stenosis and two bioprosthetic aortic valve (BioAV) designs using advanced energy-based analyses. Three-dimensional high-fidelity fluid-structure interaction simulations have been conducted and a dedicated and novel spectral analysis has been developed to characterise the kinetic energy (KE) carried by eddies in the wavenumber space. In addition, new field quantities, i.e. modal KE anisotropy intensity as well as normalised helicity intensity, are introduced. Spectral analysis shows kinetic energy (KE) decay variations, with the stenotic case aligning with Kolmogorov's theory, while BioAV cases differing. We explore the impact of flow helicity on KE transfer and decay in BioAVs. Probability distributions of modal KE anisotropy unveil flow asymmetries in the stenotic and one BioAV cases. Moreover, an inverse correlation between temporally averaged modal KE anisotropy and normalised instantaneous helicity intensity is noted, with the coefficient of determination varying among the valve configurations. Leaflet dynamics analysis highlights a stronger correlation between flow and biomechanical KE anisotropy in one BioAV due to higher leaflet displacement magnitude. These findings emphasise the role of valve architecture in aortic turbulence as well as its importance for BioAV performance and energy-based design enhancement.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part I: Flow configuration and vortex dynamics.

Aortic valve replacement has become an increasing concern due to the rising prevalence of aortic stenosis in an ageing population. Existing replacement options have limitations, necessitating the development of improved prosthetic aortic valves. In this study, flow characteristics during systole in a stenotic aortic valve case are compared with those downstream of two newly designed surgical bioprosthetic aortic valves (BioAVs). To do so, advanced three-dimensional fluid-structure interaction simulations are conducted and dedicated analysis methods to investigate jet flow configuration and vortex dynamics are developed. Our findings reveal that the stenotic case maintains a high jet flow eccentricity due to a fixed orifice geometry, resulting in flow separation and increased vortex stretching and tilting in the commissural low-flow regions. One BioAV design introduces non-axisymmetric leaflet motion, which reduces the maximum jet velocity and forms more vortical structures. The other BioAV design produces a fixed symmetric triangular jet shape due to non-moving leaflets and exhibits favourable vorticity attenuation, revealed by negative temporally and spatially averaged projected vortex stretching values, and significantly reduced drag. Therefore, this study highlights the benefits of custom-designed aortic valves in the context of their replacement through comprehensive and novel flow analyses. The results emphasise the importance of analysing jet flow, vortical structures, momentum balance and vorticity transport for thoroughly evaluating aortic valve performance.

Influence of Roasting Temperature on the Detectability of Potentially Allergenic Lupin by SDS-PAGE, ELISAs, LC-MS/MS, and Real-Time PCR.

Seeds of "sweet lupins" have been playing an increasing role in the food industry. Lupin proteins may be used for producing a variety of foods, including pasta, bread, cookies, dairy products, and coffee substitutes. In a small percentage of the population, lupin consumption may elicit allergic reactions, either due to primary sensitization to lupin or due to cross-allergy with other legumes. Thus, lupin has to be declared on commercial food products according to EU food regulations. In this study, we investigated the influence of roasting seeds of the L. angustifolius cultivar "Boregine" on the detectability of lupin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), ELISAs, LC-MS/MS, and real-time PCR. Seeds were roasted by fluidized bed roasting, and samples were drawn at seed surface temperatures ranging from 98 °C to 242 °C. With increasing roasting temperature, the extractability of proteins and DNA decreased. In addition, roasting resulted in lower detectability of lupin proteins by ELISAs and LC-MS/MS and lower detectability of DNA by real-time PCR. Our results suggest reduced allergenicity of roasted lupin seeds used for the production of "lupin coffee"; however, this has to be confirmed in in vivo studies.

Dielectric elastomer actuator-based valveless pump as Fontan failure assist device: introduction and preliminary study.

OBJECTIVES: Fontan failure refers to a condition in which the Fontan circulation, a surgical procedure used to treat certain congenital heart defects, becomes insufficient, leading to compromised cardiac function and potential complications. This in vitro study therefore investigates the feasibility of bladeless impedance-driven cavopulmonary assist device via dielectric elastomer actuator (DEA) as a means to address Fontan failure. METHODS: A cavopulmonary assist device, constructed using DEA technologies and employing the impedance pump concept, is subjected to in vitro testing within a closed-loop setup. This study aims to assess the device's functionality and performance under controlled conditions, providing valuable insights into its potential application as a cavopulmonary assistive technology. RESULTS: The DEA-based pump, measuring 50 mm in length and 30 mm in diameter, is capable of achieving substantial flow rates within a closed-loop setup, reaching up to 1.20 l/min at an activation frequency of 4 Hz. It also provides a broad range of working internal pressures (<10 to >20 mmHg). Lastly, the properties of the flow (direction, magnitude, etc.) can be controlled by adjusting the input signal parameters (frequency, amplitude, etc.). CONCLUSIONS: In summary, the results suggest that the valveless impedance-driven pump utilizing DEA technology is promising in the context of cavopulmonary assist devices. Further research and development in this area may lead to innovative and potentially more effective solutions for assisting the right heart, ultimately benefiting patients with heart-related health issues overall, with a particular focus on those experiencing Fontan failure.

Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi.

Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 µm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only 43% of all injected MT were fully occlusive. Second, it could also be shown that the maximal concentration of a dye (representing therapeutic agent) during intracoronary infusion could be increased on average by 58%, when proximally occluding the coronary artery by a balloon during drug infusion. The obtained results and insights enhance the understanding of perfusion in MVO-affected microcirculation and could lead to improved treatment methods for MVO patients.

Novel para-aortic cardiac assistance using a pre-stretched dielectric elastomer actuator.

OBJECTIVES: We propose an evolution of a dielectric elastomer actuator-based cardiac assist device that acts as a counterpulsation system. We introduce a new pre-stretched actuator and implant the device in a graft bypass between the ascending and descending aorta to redirect all blood through the device (ascending aorta clamped). The objective was to evaluate the influence of these changes on the assistance provided to the heart. METHODS: The novel para-aortic device and the new implantation technique were tested in vivo in 5 pigs. We monitored the pressure and flow in the aorta as well as the pressure-volume characteristics of the left ventricle. Different activation timings were tested to identify the optimal device actuation. RESULTS: The proposed device helps reducing the end-diastolic pressure in the aorta by up to 13 ± 4.0% as well as the peak systolic pressure by up to 16 ± 3.6%. The early diastolic pressure was also increased up to 10 ± 3.5%. With different activation, we also showed that the device could increase or decrease the stroke volume. CONCLUSIONS: The new setup and the novel para-aortic device presented here helped improve cardiac assistance compared to previous studies. Moreover, we revealed a new way to assist the heart by actuating the device at different starting time to modify the left ventricular stroke volume and stroke work.

Dielectric Elastomer Actuator-Based Valveless Impedance-Driven Pumping for Meso- and Macroscale Applications.

Impedance pumps are simple designs that allow the generation or amplification of flow. They are fluid-filled systems based on flexible tubing connected to tubing with different impedances. A periodic off-center compression of the flexible tubing causes the fluid to move and generate flow. Wave reflection at the impedance mismatch is the primary driving mechanism of the flow. In addition to their straightforward design, impedance pumps are bladeless, valveless, and pulsatile. These properties are highly sought after by demanding and challenging applications, such as the biomedical field, as they present less risk of damage, disruption, and obstruction when handling viscous and delicate fluids/matter. In this study, we propose a high-performance impedance-driven pumping concept with embedded actuation based on a multilayered tubular dielectric elastomer. This pumping system is made of three parts, a dielectric elastomer actuator tube, a passive tube, and a rigid ring that binds and decouples the two subsystems. The system is able to generate net fluid flow rates up to 1.35 L/min with an internal pressure of 125 mmHg. The soft simplistic design, self-contained concept, and high performances of these pumping systems could make them disruptive in many challenging meso- and macroscale applications in general and in the biomedical field in particular.

Wall Shear Stress and Pressure Fluctuations under Oscillating Stimulation in Helical Square Ducts with Cochlea-like Geometrical Curvature and Torsion.

Our study aims to provide basic insights on the impact of the spiral shape of the cochlea, i.e., of geometric torsion and curvature, on wall pressure and wall shear stress. We employed computational fluid dynamics in square duct models with curvature and torsion similar to those found in human cochleae. The results include wall pressures and wall shear stresses within the ducts under oscillating axial flow. Our findings indicate that the helical shape generates higher transverse wall shear stresses compared to exclusively curved or twisted ducts. The wall pressures and transverse wall shear stresses we found rise to amounts that may be physiologically relevant in the cochlea.Clinical relevance- The role of the spiral shape of the cochlea in hearing physiology remains, for a large part, elusive. For a better apprehension of hearing and its disorders, it is important to investigate the influence of geometric properties on biofluids motion and emerging phenomena in the cochlea.

Altered blood flow due to larger aortic diameters in patients with transcatheter heart valve thrombosis.

The etiology of transcatheter heart valve thrombosis (THVT) and the relevance of the aortic root geometry on the occurrence of THVT are largely unknown. The first aim of this pilot study is to identify differences in aortic root geometry between THVT patients and patients without THVT after transcatheter aortic valve implantation (TAVI). Second, we aim to investigate how the observed difference in aortic diameters affects the aortic flow using idealized computational geometric models. Aortic dimension was assessed using pre-TAVI multi-detector computed tomography scans of eight patients with clinical apparent THVT and 16 unaffected patients (two for each THVT patient with same valve type and size) from the Bern-TAVI registry. Among patients with THVT the right coronary artery height was lower (-40%), and sinotubular junction (STJ) and ascending aorta (AAo) diameters tended to be larger (9% and 14%, respectively) compared to the unaffected patients. Fluid-structure interaction (FSI) in two idealized aortic models with the observed differences in STJ and AAo diameter showed higher backflow rate at the STJ (+16%), lower velocity magnitudes in the sinus (-5%), and higher systolic turbulent dissipation rate in the AAo (+8%) in the model with larger STJ and AAo diameters. This pilot study suggests a direct effect of the aortic dimensions on clinically apparent THVT. The FSI study indicates that larger STJ and AAo diameters potentially favor thrombus formation by increased backflow rate and reduced wash-out efficiency of the sinus. The reported observations require clinical validation but could potentially help identifying patients at risk for THVT.

Application of Patient-Specific Computational Fluid Dynamics in Anomalous Aortic Origin of Coronary Artery: A Systematic Review.

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart condition with fixed and dynamic stenotic elements, potentially causing ischemia. Invasive coronary angiography under stress is the established method for assessing hemodynamics in AAOCA, yet it is costly, technically intricate, and uncomfortable. Computational fluid dynamics (CFD) simulations offer a noninvasive alternative for patient-specific hemodynamic analysis in AAOCA. This systematic review examines the role of CFD simulations in AAOCA, encompassing patient-specific modeling, noninvasive imaging-based boundary conditions, and flow characteristics. Screening articles using AAOCA and CFD-related terms prior to February 2023 yielded 19 publications, covering 370 patients. Over the past four years, 12 (63%) publications (259 patients) employed dedicated CFD models, whereas 7 (37%) publications (111 patients) used general-purpose CFD models. Dedicated CFD models were validated for fixed stenosis but lacked dynamic component representation. General-purpose CFD models exhibited variability and limitations, with fluid-solid interaction models showing promise. Interest in CFD modeling of AAOCA has surged recently, mainly utilizing dedicated models. However, these models inadequately replicate hemodynamics, necessitating novel CFD approaches to accurately simulate pathophysiological changes in AAOCA under stress conditions.

Hemodynamic effects of a dielectric elastomer augmented aorta on aortic wave intensity: An in-vivo study.

Dielectric elastomer actuator augmented aorta (DEA) represents a novel approach with high potential for assisting a failing heart. The soft tubular device replaces a section of the aorta and increases its diameter when activated. The hemodynamic interaction between the DEA and the left ventricle (LV) has not been investigated with wave intensity (WI) analysis before. The objective of this study is to investigate the hemodynamic effects of the DEA on the aortic WI pattern. WI was calculated from aortic pressure and flow measured in-vivo in the descending aorta of two pigs implanted with DEAs. The DEAs were tested for different actuation phase shifts (PS). The DEA generated two decompression waves (traveling upstream and downstream of the device) at activation followed by two compression waves at deactivation. Depending on the PS, the end-diastolic pressure (EDP) decreased by 7% (or increased by 5-6%). The average early diastolic pressure augmentation (Pdia¯) increased by 2% (or decreased by 2-3%). The hydraulic work (WH) measured in the aorta decreased by 2% (or increased by 5%). The DEA-generated waves interfered with the LV-generated waves, and the timing of the waves affected the hemodynamic effect of the device. For the best actuation timing the upstream decompression wave arrived just before aortic valve opening and the upstream compression wave arrived just before aortic valve closure leading to a decreased EDP, an increased Pdia¯ and a reduced.WH.

Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves.

Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. STATEMENT OF SIGNIFICANCE: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.

Biogenic polymer-based patches for congenital cardiac surgery: a feasibility study.

Objective: Currently used patch materials in congenital cardiac surgery do not grow, renew, or remodel. Patch calcification occurs more rapidly in pediatric patients eventually leading to reoperations. Bacterial cellulose (BC) as a biogenic polymer offers high tensile strength, biocompatibility, and hemocompatibility. Thus, we further investigated the biomechanical properties of BC for use as patch material. Methods: The BC-producing bacteria Acetobacter xylinum were cultured in different environments to investigate optimal culturing conditions. For mechanical characterization, an established method of inflation for biaxial testing was used. The applied static pressure and deflection height of the BC patch were measured. Furthermore, a displacement and strain distribution analysis was performed and compared to a standard xenograft pericardial patch. Results: The examination of the culturing conditions revealed that the BC became homogenous and stable when cultivated at 29°C, 60% oxygen concentration, and culturing medium exchange every third day for a total culturing period of 12 days. The estimated elastic modulus of the BC patches ranged from 200 to 530 MPa compared to 230 MPa for the pericardial patch. The strain distributions, calculated from preloaded (2 mmHg) to 80 mmHg inflation, show BC patch strains ranging between 0.6% and 4%, which was comparable to the pericardial patch. However, the pressure at rupture and peak deflection height varied greatly, ranging from 67 to around 200 mmHg and 0.96 to 5.28 mm, respectively. The same patch thickness does not automatically result in the same material properties indicating that the manufacturing conditions have a significant impact on durability. Conclusions: BC patches can achieve comparable results to pericardial patches in terms of strain behavior as well as in the maximum applied pressure that can be withstood without rupture. Bacterial cellulose patches could be a promising material worth further research.

A novel soft cardiac assist device based on a dielectric elastomer augmented aorta: An in vivo study.

Although heart transplant is the preferred solution for patients suffering from heart failures, cardiac assist devices remain key substitute therapies. Among them, aortic augmentation using dielectric elastomer actuators (DEAs) might be an alternative technological application for the future. The electrically driven actuator does not require bulky pneumatic elements (such as conventional intra-aortic balloon pumps) and conforms tightly to the aorta thanks to the manufacturing method presented here. In this study, the proposed DEA-based device replaces a section of the aorta and acts as a counterpulsation device. The feasibility and validation of in vivo implantation of the device into the descending aorta in a porcine model, and the level of support provided to the heart are investigated. Additionally, the influence of the activation profile and delay compared to the start of systole is studied. We demonstrate that an activation of the DEA just before the start of systole (30 ms at 100 bpm) and deactivation just after the start of diastole (0-30 ms) leads to an optimal assistance of the heart with a maximum energy provided by the DEA. The end-diastolic and left ventricular pressures were lowered by up to 5% and 1%, respectively, compared to baseline. The early diastolic pressure was augmented in average by up to 2%.

Fluid mechanical performance of ureteral stents: The role of side hole and lumen size.

Ureteral stents are indispensable devices in urological practice to maintain and reinstate the drainage of urine in the upper urinary tract. Most ureteral stents feature openings in the stent wall, referred to as side holes (SHs), which are designed to facilitate urine flux in and out of the stent lumen. However, systematic discussions on the role of SH and stent lumen size in regulating flux and shear stress levels are still lacking. In this study, we leveraged both experimental and numerical methods, using microscopic-Particle Image Velocimetry and Computational Fluid Dynamic models, respectively, to explore the influence of varying SH and lumen diameters. Our results showed that by reducing the SH diameter from 1.1 to 0.4 mm the median wall shear stress levels of the SHs near the ureteropelvic junction and ureterovesical junction increased by over 150 % , even though the flux magnitudes through these SH decreased by about 40 % . All other SHs were associated with low flux and low shear stress levels. Reducing the stent lumen diameter significantly impeded the luminal flow and the flux through SHs. By means of zero-dimensional models and scaling relations, we summarized previous findings on the subject and argued that the design of stent inlet/outlet is key in regulating the flow characteristics described above. Finally, we offered some clinically relevant input in terms of choosing the right stent for the right patient.

Enhanced Drug Delivery for Cardiac Microvascular Obstruction with an Occlusion-Infusion-Catheter.

Microvascular Obstruction (MVO) is a common consequence of acute myocardial infarction. MVO is underdiagnosed and treatment is often nonspecific and ineffective. A multi-scale in-vitro benchtop model was established to investigate drug perfusion in MVO affected microcirculation. The central element of the benchtop model was a fluidic microchip containing channels with diameters between [Formula: see text] and 50 µm representing [Formula: see text] of the microvascular tree fed by the left anterior descending artery (LAD). The outlets of the chip could be closed to mimic MVO. Two methods for intracoronary infusion of pharmacologic agents (simulated by dye) to regions with MVO were investigated using an occlusion-infusion catheter. The first case was a simple, bolus-like infusion into the LAD, whereas the second case consisted of infusion with concomitant proximal occlusion of the LAD phantom with a balloon. Results show that local dye concentration maxima in the chip with MVO were 2.2-3.2 times higher for the case with proximal balloon occlusion than for the conventional infusion method. The cumulated dose could be raised by a factor 4.6-5.2. These results suggest that drug infusion by catheter is more effective if the blood supply to the treated vascular bed is temporarily blocked by a balloon catheter.

HPC+ in the medical field: Overview and current examples.

BACKGROUND: To say data is revolutionising the medical sector would be a vast understatement. The amount of medical data available today is unprecedented and has the potential to enable to date unseen forms of healthcare. To process this huge amount of data, an equally huge amount of computing power is required, which cannot be provided by regular desktop computers. These areas can be (and already are) supported by High-Performance-Computing (HPC), High-Performance Data Analytics (HPDA), and AI (together "HPC+"). OBJECTIVE: This overview article aims to show state-of-the-art examples of studies supported by the National Competence Centres (NCCs) in HPC+ within the EuroCC project, employing HPC, HPDA and AI for medical applications. METHOD: The included studies on different applications of HPC in the medical sector were sourced from the National Competence Centres in HPC and compiled into an overview article. Methods include the application of HPC+ for medical image processing, high-performance medical and pharmaceutical data analytics, an application for pediatric dosimetry, and a cloud-based HPC platform to support systemic pulmonary shunting procedures. RESULTS: This article showcases state-of-the-art applications and large-scale data analytics in the medical sector employing HPC+ within surgery, medical image processing in diagnostics, nutritional support of patients in hospitals, treating congenital heart diseases in children, and within basic research. CONCLUSION: HPC+ support scientific fields from research to industrial applications in the medical area, enabling researchers to run faster and more complex calculations, simulations and data analyses for the direct benefit of patients, doctors, clinicians and as an accelerator for medical research.

An in vitro bladder model with physiological dynamics: Vesicoureteral reflux alters stent encrustation pattern.

In vitro models are indispensable to study the physio-mechanical characteristics of the urinary tract and to evaluate ureteral stent performances. Yet previous models mimicking the urinary bladder have been limited to static or complicated systems. In this study, we designed a simple in vitro bladder model to simulate the dynamics of filling and voiding. The physio-mechanical condition of the model was verified using a pressure-flow test with different bladder outlet obstruction levels, and a reflux test was performed to qualitatively demonstrate the stent associated vesicoureteral reflux (VUR). Finally, the setup was applied with and without the bladder model to perform encrustation tests with artificial urine on commercially available double-J stents, and the volumes of luminal encrustations were quantified using micro-Computed Tomography and image segmentation. Our results suggest that, VUR is an important factor contributing to the dynamics in the upper urinary tract with indwelling stents, especially in patients with higher bladder outlet obstruction levels. The influence of VUR should be properly addressed in future in vitro studies and clinical analyses.