Explore the vast range of titles available.

The hemodynamic benefit of novel arteriovenous graft (AVG) designs is typically assessed using computational models that assume highly idealized graft configurations and/or simplified boundary conditions representing the peripheral vasculature. The objective of this study is to evaluate whether idealized AVG models are suitable for hemodynamic evaluation of new graft designs, or whether more realistic models are required. An idealized and a realistic, clinical imaging based, parametrized AVG geometry were created. Furthermore, two physiological boundary condition models were developed to represent the peripheral vasculature. We assessed how graft geometry (idealized or realistic) and applied boundary condition models of the peripheral vasculature (physiological or distal zero-flow) impacted hemodynamic metrics related to AVG dysfunction. Anastomotic regions exposed to high WSS (>7, [less than or equal to]40 Pa), very high WSS (>40 Pa) and highly oscillatory WSS were larger in the simulations using the realistic AVG geometry. The magnitude of velocity perturbations in the venous segment was up to 1.7 times larger in the realistic AVG geometry compared to the idealized one. When applying a (non-physiological zero-flow) boundary condition that neglected blood flow to and from the peripheral vasculature, we observed large regions exposed to highly oscillatory WSS. These regions could not be observed when using either of the newly developed distal boundary condition models. Hemodynamic metrics related to AVG dysfunction are highly dependent on the geometry and the distal boundary condition model used. Consequently, the hemodynamic benefit of a novel graft design can be misrepresented when using idealized AVG modelling setups.

Compliance mismatch between an arteriovenous dialysis graft (AVG) and the connected vein is believed to result in disturbed haemodynamics around the graft–vein anastomosis and increased mechanical loading of the vein. Both phenomena are associated with neointimal hyperplasia development, which is the main reason for AVG patency loss. In this study, we use a patient-specific fluid structure interaction AVG model to assess whether AVG haemodynamics and mechanical loading can be optimised by using novel electrospun polyurethane (ePU) grafts, since their compliance can be better tuned to match that of the native veins, compared to gold standard, expanded polytetrafluoroethylene (ePTFE) grafts. It was observed that the magnitude of flow disturbances in the vein and the size of anastomotic areas exposed to highly oscillatory shear (OSI>0.25) and very high wall shear stress (>40Pa) were largest for the ePTFE graft. Median strain and von Mises stress in the vein were similar for both graft types, whereas highest stress and strain were observed in the anastomosis of the ePU graft. Since haemodynamics were most favourable for the ePU graft simulation, AVG longevity might be improved by the use of ePU grafts.

Background Integration of a patient’s non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019–10–07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013–11–12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. Results A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2  < 1.6), but minimum parameter reproducibility was poor ( ICC min  = 0.01). Iterative reduction yielded a reproducible ( ICC min  = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2  < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs ( p  < 0.05). Conclusions By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient’s underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

We developed a whole-circulation computational model by integrating a transmission line (TL) model describing vascular wave transmission into the established CircAdapt platform of whole-heart mechanics. In the present paper, we verify the numerical framework of our TL model by benchmark comparison to a previously validated pulse wave propagation (PWP) model. Additionally, we showcase the integrated CircAdapt-TL model, which now includes the heart as well as extensive arterial and venous trees with terminal impedances. We present CircAdapt-TL haemodynamics simulations of: 1) a systemic normotensive situation and 2) a systemic hypertensive situation. In the TL-PWP benchmark comparison we found good agreement regarding pressure and flow waveforms (relative errors ≤ 2.9% for pressure, and ≤ 5.6% for flow). CircAdapt-TL simulations reproduced the typically observed haemodynamic changes with hypertension, expressed by increases in mean and pulsatile blood pressures, and increased arterial pulse wave velocity. We observed a change in the timing of pressure augmentation (defined as a late-systolic boost in aortic pressure) from occurring after time of peak systolic pressure in the normotensive situation, to occurring prior to time of peak pressure in the hypertensive situation. The pressure augmentation could not be observed when the systemic circulation was lumped into a (non-linear) three-element windkessel model, instead of using our TL model. Wave intensity analysis at the carotid artery indicated earlier arrival of reflected waves with hypertension as compared to normotension, in good qualitative agreement with findings in patients. In conclusion, we successfully embedded a TL model as a vascular module into the CircAdapt platform. The integrated CircAdapt-TL model allows detailed studies on mechanistic studies on heart-vessel interaction.

Disturbed shear stress is thought to be the driving factor of neointimal hyperplasia in blood vessels and grafts, for example in hemodialysis conduits. Despite the common occurrence of neointimal hyperplasia, however, the mechanistic role of shear stress is unclear. This is especially problematic in the context of in situ scaffold-guided vascular regeneration, a process strongly driven by the scaffold mechanical environment. To address this issue, we herein introduce an integrated numerical-experimental approach to reconstruct the graft–host response and interrogate the mechanoregulation in dialysis grafts. Starting from patient data, we numerically analyze the biomechanics at the vein–graft anastomosis of a hemodialysis conduit. Using this biomechanical data, we show in an in vitro vascular growth model that oscillatory shear stress, in the presence of cyclic strain, favors neotissue development by reducing the secretion of remodeling markers by vascular cells and promoting the formation of a dense and disorganized collagen network. These findings identify scaffold-based shielding of cells from oscillatory shear stress as a potential handle to inhibit neointimal hyperplasia in grafts.van Haaften et al. show numerical-experimental approach to reconstruct the graft–host response. They interrogate the mechanoregulation in dialysis grafts to solve the disturbed shear stress problem, which can be a cause of neointimal hyperplasia in blood vessels and grafts.

Aortic stenosis (AS) is a common valvular disease becoming more prevalent globally due to the aging of the population. Transcatheter aortic valve implantation (TAVI) is a minimally invasive intervention indicated for AS patients as alternative to surgical replacement. TAVI is to date an established procedure. However, it has been often associated with complications such as paravalvular leakage (PVL) or conduction abnormalities. Evidence of associations between morphological features of the aortic root, valve calcification measurements and suboptimal procedural outcomes have been suggested but the analyses were limited by availability and reproducibility of clinical measurements. In this work, we aim to enrich the characterization of AS patients referred for TAVI by analyzing the clinical findings in conjunction with advanced morphological analysis of the implantation site including aortic root, left ventricular outflow tract and 3D calcification patterns. A population of consecutive patients with AS (n = 130) who underwent TAVI at our clinical centre were retrospectively selected for this study. Demographic and clinical measurements were collected before and after TAVI. Pre-operative CT images were used to reconstruct 3D models of patient-specific anatomies. Statistical shape modelling was carried out and outcomes were analyzed in conjunction with clinical outcomes. The 3D modelling of the valve calcification rate matched previous clinical descriptions; including the crescent shapes visible on each leaflet and the higher calcification rate of the non-coronary cusp. Higher calcification rate was found in larger valves together with a positive association between each coronary height and the calcification of their respective leaflet. Sexual dimorphism, on both shape and calcification, was recorded beyond the size differences with straighter aortas and higher calcification rate at the junction between the left and right coronary leaflets for males compared to females. Morphological differences were significantly associated (p = 0.005) with PVL assessments based on post-operative echocardiograms. Larger aortas and shorter left coronary sinus were associated with less leakage. The outcome distribution appeared to be directly affected by sexual differences and device design. Female phenotypes, smaller and more conic aortic root, were associated with worse outcome. Different patterns in calcification distribution on the leaflets were identified but the association with outcomes is not conclusive. In the future, the presented morphological characterization of patients with AS could contribute to predict post-TAVI PVL and design and test improved TAVI devices.

Mechanical properties of an aneurysmatic thoracic aorta are potential markers of future growth and remodelling and can help to estimate the risk of rupture. Aortic geometries obtained from routine medical imaging do not display wall stress distribution and mechanical properties. Mechanical properties for a given vessel may be determined from medical images at different physiological pressures using inverse finite element analysis. However, without considering pre-stresses, the estimation of mechanical properties will lack accuracy. In the present paper, we propose and evaluate a mechanical parameter identification technique, which recovers pre-stresses by determining the zero-pressure configuration of the aortic geometry. We first validated the method on a cylindrical geometry and subsequently applied it to a realistic aortic geometry. The verification of the assessed parameters was performed using synthetically generated reference data for both geometries. The method was able to estimate the true mechanical properties with an accuracy ranging from 98% to 99%.

Local biaxial deformation measurements are essential for the in-depth investigation of tissue properties and remodeling of the ascending thoracic aorta, particularly in aneurysm formation. Current clinical imaging modalities pose limitations around the resolution and tracking of anatomical markers. We evaluated a new intra-operative video-based method to assess local biaxial strains of the ascending thoracic aorta. In 30 patients undergoing open-chest surgery, we obtained repeated biaxial strain measurements, at low- and high-pressure conditions. Precision was very acceptable, with coefficients of variation for biaxial strains remaining below 20%. With our four-marker arrangement, we were able to detect significant local differences in the longitudinal strain as well as in circumferential strain. Overall, the magnitude of strains we obtained (range: 0.02–0.05) was in line with previous reports using other modalities. The proposed method enables the assessment of local aortic biaxial strains and may enable new, clinically informed mechanistic studies using biomechanical modeling as well as mechanobiological profiling.

Background Mathematical modelling of pressure and flow waveforms in blood vessels using pulse wave propagation (PWP) models could support clinical decision-making. For a personalised model outcome, measurements of all modelled vessel radii and wall thicknesses are required. In clinical practice, however, datasets are often incomplete. To overcome this problem, we hypothesised that the adaptive capacity of blood vessels in response to mechanical load can be utilised to fill in the gaps of incomplete patient-specific datasets. Methods We implemented homeostatic feedback loops in a validated PWP model [ 1 ] to allow adaptation of vessel geometry to maintain wall stress and wall shear stress. To evaluate our approach, we utilised complete datasets of 10 patients scheduled for vascular access surgery. Datasets comprised of wall thicknesses and radii of 7 central and 11 arm arterial segments. We simulated reference models (RefModel, n = 10) using complete data and adapted models (AdaptModel, n = 10) using data of one brachial artery segment only. The remaining AdaptModel geometries were estimated using adaptation. In both models, mean brachial pressure, brachial artery distensibility, heart rate and aortic inflow were prescribed. We evaluated agreement between RefModel and AdaptModel geometries, as well as between pressure and flow waveforms of both models. Results Limits of agreement (bias ± 1.96SD) between AdaptModel and RefModel radii and wall thicknesses were 0.029 ± 1.3mm and 28 ± 230µm, respectively. AdaptModel pressure and flow waveform characteristics across the proximal-to-distal arterial domain were within the uncertainty bounds of the RefModel ( Fig. 1 ). Figure 1 AdaptModel and RefModel pressure and flow waveforms at three arterial locations. For adequate comparison between the AdaptModel and the RefModel a total of 100 RefModel realisations were generated within the measurement uncertainty. The median RefModel is indicated by the blue dotted curves. Conclusions Our adaptation-based PWP model enables personalisation even when not all required data is available.

Background Dysfunctional cellular mechanosensing appears central to aneurysm formation [ 1 ]. We aimed to derive material parameters of aneurysm tissue from in vivo deformations, which may increase insight into the underlying structural integrity of the pathological tissue. Methods Videos of tracking markers (example Video in supplement, screenshot in Figure) placed on ascending aortic segments were captured alongside radial arterial blood pressure in patients undergoing open-thorax ascending thoracic aorta aneurysm (ATAA) repair ( n = 5) and coronary bypass (controls; n = 2). Normalised cross-correlation was used to determine marker displacements, resulting in estimates of systolic/diastolic diameters, distensibility, and cyclic axial engineering strain. A thinwalled, cylindrical geometry was assumed, with amorphous (Neo-Hookean) and fibrous (two-family) constitutive contributions [ 2 ]. This framework was fitted to individual patient measurements, by varying parameters c (amorphous material constant), k 1 and k 2 (fiber stiffness and strain stiffening parameter), β (fiber angle w.r.t. circumferential direction), unloaded intact length ( L ), and internal radius ( R i ). Results Axial strain tended to be lower (expected) and distensibility larger (unexpected) in aneurysm than controls (Figure). However, the intrinsic pressure-dependence of distensibility must be considered when drawing conclusions related to differences in structural stiffness between both groups [ 3 ]. Material stiffness parameters ( c and k 1 ) appeared higher in aneurysm patients than in controls which is in line with previous studies in mice [ 4 ]. Conclusion We are developing a method to determine ATAA material properties from in vivo deformations and observed increased material stiffness in ATAA. Aneurysm Control Measured outcomes Diastolic diameter [mm] 40 ± 5 23 ± 3 DBP [mmHg] 58 ± 11 34 ± 2 SBP [mmHg] 90 ± 18 93 ± 7 Distensibility [MPa –1 ] 4.3 ± 3.0 3.7 ± 1.1 Axial strain [%] 4.3 ± 2.1 7.6 ± 3.5 Estimated properties c [kPa] 37 ± 29 15 ± 13 k [kPa] 43 ± 26 24 ± 24 R 1 [mm] 17 ± 1 10 ± 1 β [degrees] 35 ± 3 36 ± 2 k 2 – 34 ± 9 37 ± 3 L [mm] 24 ± 5 15 ± 2 Figure Left: Example of ascending aortic region of interest with tracking markers. Right: Data presented as mean ± standard deviation. SBP/DBP, systolic/diastolic blood pressure. Estimated properties are defined in the text.