Potential Thrombus Formation Research Articles

Decellularized porcine vena cava grafts are fully repopulated after orthotopic implantation

Tissue-engineered organs, based on native extracellular matrix (ECM) scaffolds, could be a game changer in regenerative medicine applications. Decellularization technology provides such scaffolds with organ-typic ECM composition and architecture. Despite limitations such as the requirement of huge cell numbers and finding the optimal route of entry, recellularized scaffolds provide alternative grafts for transplantation. In this study we assessed whether decellularized scaffolds, when implanted, are repopulated from the adjacent tissue. Since the vasculature plays an important role in tissue functionality, our main focus was to evaluate in situ repopulation of decellularized veins in a pig model. For this, porcine inferior vena cava grafts were decellularized and orthotopically implanted in recipient pigs (n = 12). To evaluate possible immune responses to the scaffolds and to assess potential thrombus formation, cellular allogeneic vena cava grafts were transplanted in control pigs (n = 8). Within 28 days after implantation, the decellularized veins were fully recellularized with endothelial cells and smooth muscle cells. Quantitative histological analysis showed a comparable amount of smooth muscle actin in the repopulated decellularized grafts similar to the native IVC. Lymphocyte infiltrates representing signs of graft rejection were not detected in the pigs, as opposed to the control group that received the allogeneic grafts. The decellularized grafts provoked a higher incidence of thrombosis in comparison with allogeneic grafts (33.3 vs. 12.5%). With this study, we show efficient in situ repopulation of decellularized vein grafts. These findings are insightful and promising to further explore the use of decellularized tissue without the need for full pre-transplant recellularization.Graphical abstract

ADAMTS13 or Caplacizumab Reduces the Accumulation of Neutrophil Extracellular Traps and Thrombus in Whole Blood of COVID-19 Patients under Flow.

Neutrophil NETosis and neutrophil extracellular traps (NETs) play a critical role in pathogenesis of coronavirus disease 2019 (COVID-19)-associated thrombosis. However, the extents and reserve of NETosis, and potential of thrombus formation under shear in whole blood of patients with COVID-19 are not fully elucidated. Neither has the role of recombinant ADAMTS13 or caplacizumab on the accumulation of NETs and thrombus in COVID-19 patients' whole blood under shear been investigated. Flow cytometry and microfluidic assay, as well as immunoassays, were employed for the study. We demonstrated that the percentage of H3Cit + MPO+ neutrophils, indicative of NETosis, was dramatically increased in patients with severe but not critical COVID-19 compared with that in asymptomatic or mild disease controls. Upon stimulation with poly [I:C], a double strain DNA mimicking viral infection, or bacterial shigatoxin-2, the percentage of H3Cit + MPO+ neutrophils was not significantly increased in the whole blood of severe and critical COVID-19 patients compared with that of asymptomatic controls, suggesting the reduction in NETosis reserve in these patients. Microfluidic assay demonstrated that the accumulation of NETs and thrombus was significantly enhanced in the whole blood of severe/critical COVID-19 patients compared with that of asymptomatic controls. Like DNase I, recombinant ADAMTS13 or caplacizumab dramatically reduced the NETs accumulation and thrombus formation under arterial shear. Significantly increased neutrophil NETosis, reduced NETosis reserve, and enhanced thrombus formation under arterial shear may play a crucial role in the pathogenesis of COVID-19-associated coagulopathy. Recombinant ADAMTS13 or caplacizumab may be explored for the treatment of COVID-19-associated thrombosis.

Longitudinal investigation of aortic dissection in mice with computational fluid dynamics

Predicting late adverse events in aortic dissections is challenging. One commonly observed risk factor is partial thrombosis of the false lumen. In this study we investigated false lumen thrombus progression over 7 days in four mice with angiotensin II-induced aortic dissection. We performed computational fluid dynamic simulations with subject-specific boundary conditions from velocity and pressure measurements. We investigated endothelial cell activation potential, mean velocity, thrombus formation potential, and other hemodynamic factors. Our findings support the hypothesis that flow stagnation is the predominant hemodynamic factor driving a large thrombus ratio in false lumina, particularly those with a single fenestration.

P36: Filling the Gap: Developing the Penn State University Child Pump

Study: Despite the need for suitable Mechanical Circulatory Support (MCS) for pediatric patients between 10 and 30 kg, there are currently no long-term implantable devices for this patient cohort. In order to address this need, we are developing the Penn State Child Pump, a continuous flow ventricular assist device (cf-VAD) that will remove the risks of device size mismatch and running at suboptimal operating conditions. Methods: A prototype PSU Child Pump was manufactured based on our experiences with adult cf-LVADs and cf-RVADs. The pump size was tailored to the average chest size of the target pediatric patient population (Figure 1A). In-vitro hemolysis was evaluated under three conditions on our small volume mock circulatory loop with bovine blood (Figure 1B): 1) 8300 RPM, ΔP = 60 mmHg, 3.5 LPM; 2) 8200 RPM, ΔP = 20 mmHg, 5.1 LPM; 3) 8400 RPM, ΔP = 70 mmHg, 3.2 LPM. Results: The initial design of the device has an approximate 38% reduction in size compared to our adult cf-VAD. A mock fit study was conducted using a 3D printed model of a 19 kg patient’s thoracic cavity to compare the size of the PSU Child Pump to the HVAD (Medtronic, Minneapolis, MN) (Figure 1A). In-vitro testing revealed the hemolysis levels at conditions 1, 2, and 3 were 0.037 mg/dL, 0.022 mg/dL, and 0.021 mg/dL, respectively (Figure 1C). Conclusions: The PSU Child Pump prototype was constructed and evaluated, yielding initial results indicating promising hemocompatibility under the given testing conditions. Using a computational fluid dynamics-based optimization platform, the PSU Child Pump will be optimized to meet maximum physiological requirements while minimizing the potential for thrombus formation, plasma-free hemoglobin levels, and degradation of von Willebrand factor. The in-silico optimization results will be validated through a series of 30-day in-vivo studies in sheep.

Fluid-structure interaction study for biomechanics and risk factors in Stanford type A aortic dissection.

Aortic dissection is a life-threatening condition with a rising prevalence in the elderly population, possibly as a consequence of the increasing population life expectancy. Untreated aortic dissection can lead to myocardial infarction, aortic branch malperfusion or occlusion, rupture, aneurysm formation and death. This study aims to assess the potential of a biomechanical model in predicting the risks of a non-dilated thoracic aorta with Stanford type A dissection. To achieve this, a fully coupled fluid-structure interaction model was developed under realistic blood flow conditions. This model of the aorta was developed by considering three-dimensional artery geometry, multiple artery layers, hyperelastic artery wall, in vivo-based physiological time-varying blood velocity profiles, and non-Newtonian blood behaviours. The results demonstrate that in a thoracic aorta with Stanford type A dissection, the wall shear stress (WSS) is significantly low in the ascending aorta and false lumen, leading to potential aortic dilation and thrombus formation. The results also reveal that the WSS is highly related to blood flow patterns. The aortic arch region near the brachiocephalic and left common carotid artery is prone to rupture, showing a good agreement with the clinical reports. The results have been translated into their potential clinical relevance by revealing the role of the stress state, WSS and flow characteristics as the main parameters affecting lesion progression, including rupture and aneurysm. The developed model can be tailored for patient-specific studies and utilised as a predictive tool to estimate aneurysm growth and initiation of wall rupture inside the human thoracic aorta.

Analysis of thrombosis risk of commissural misaligned transcatheter aortic valve prostheses using particle image velocimetry

Abstract Due to excellent clinical results, transcatheter aortic valve replacement (TAVR) has evolved to a treatment option for patients with low surgical risk, resulting in an increasing demand for durable heart valve prostheses. Durability of TAVR could be limited by leaflet thrombosis. Thrombus formation in the aortic root is mainly affected by the hemodynamic situation, which is dependent on the positioning of the implant. We investigated the flow field in the aortic root after TAVR implantation by means of particle image velocimetry. To quantify the influence of the implant-position with respect to an alignment or misalignment of the leaflet commissures on the thrombogenic potential, we used a transport equation for residence time (RT) to consider washout behavior. Furthermore, we introduced a shear effect criterion (SIE) to address platelet activation as a measure for a potential thrombus formation. Misaligned implantation of a TAVR resulted in a reversed direction of rotation of the occurring recirculation area. This led to fluid flow with comparable areas of increased relative blood RT (RTaligned: 97.6%, RTmisaligned: 88.0%) and a smaller area of low shear load for the misaligned TAVR (SIEaligned: 57.7%, SIEmisaligned: 3.70%) into the sinus region, indicating a higher potential for thrombus formation.

A Disintegrin and Metalloprotease 10 Expressions Modulate Potential Metastatic and Thrombus Formation in Pancreatic Carcinoma.

Background:Clinical investigations repurposing a disintegrin and metalloproteases 10 (ADAM10) as metastatic and thrombus marker have achieved encouraging results, but the mechanism behind this association remains unclear.Methods:This study was carried out in NingXia and Wuhan, China from 2017 to 2021. The effects of ADAM10 expression on the metastatic and thrombus-associated genes: tissue factor (TF), P-selectin glycoprotein ligand-1 (PSGL-1), cathepsin G (CTSG) and mucin 1 (MUC1) were examined by immunofluorescence, qRTPCR and Western blotting analysis. Metastatic and thrombotic behaviors were evaluated using NODSCID mouse model.Results:The ADAM10 expression controlled the migration and invasion of pancreatic carcinoma cell-1(PANC-1), and significantly regulated the metastatic and thrombus-associated genes (P<0.05). ADAM10 and MUC1 were regulated and aberrantly expressed by a dependent mechanism. Moreover, ADAM10 expression induced the progression of adenocarcinoma cells and thrombus formation in vivo.Conclusion:Regulation of ADAM10 expression in cancer cells might effectively pave the way for a more potent anti-metastatic and anti-thrombotic approach and could regulate the invasion and migration of cancer cells.

Flow residence time in intracranial aneurysms evaluated by in vitro 4D flow MRI

The process of an intracranial aneurysm development, growth, and rupture is multifaceted and complex. In addition, clinical observations have identified the potential of thrombus formation within such aneurysms. While the underlying mechanism is not fully understood, the thrombi represent a potential risk factor for ischemic stroke. Emerging studies indicate that blood residence time (RT) is a promising hemodynamic metric associated with the aneurysm rupture and formation of intra-aneurysmal thrombi. Here, we present a methodology to experimentally evaluate both trajectory-wise and local RT based on magnetic resonance imaging (MRI) velocimetry, and apply it to in vitro flow measurements in scaled-up replicas of 9 patient-specific intracranial aneurysms. Lagrangian tracks of massless tracers are integrated from the velocity fields and averaged to return the mean RT in the aneurysm sac. This is found to be closely approximated by a simple time scale based on the sac diameter and space–time average of the aneurysmal fluid velocity. The mean RT is also correlated with the inflow time scale at the parent artery. These results also provide a basis for the estimation of RT when high-resolution hemodynamic maps are not available. With the continuous increase in accuracy and resolution enabled by progress in MRI technology, the methodology described here may in the future be applicable to in vivo data.

Prevalence of Left Atrial Septal Pouch Among Patients with Embolic Stroke of Undetermined Source Or Stroke of Known Etiology: a Retrospective Study.

Background and objectivesCryptogenic strokes can be defined by the criteria established for an embolic stroke of undetermined source (ESUS). Some embolic events might be caused by a left atrial septal pouch (LASP), due to the potential of thrombus formation. In this study we aimed to determine if LASP is a risk factor for ESUS when compared to a population of strokes of known origin, the LASP screening rate in our institution and if LASP dimensions influences the risk of ESUS.MethodsWe retrospectively analyzed transesophageal echocardiograms (TEEs) in a large cohort of patients that had experienced ischemic strokes. Two authors performed blinded, independent searches for LASPs by reviewing 1152 TEEs from patients that had experienced a stroke or transient ischemic attack. We excluded 26 TEEs, due to incorrect imaging. Next, we reviewed patient medical files.ResultsAmong the 1126 included patients, 148 had an ESUS (ESUS+ group) and 978 had strokes of known origin (ESUS– group). A LASP was present in 176 patients, including 32 patients (21.6% of LASPs) in the ESUS+ group and 144 patients (14.7% of LASPs) in the ESUS– group. In multivariate analysis, LASP was independently associated with ESUS (P = 0,019). 61.9% of LASPs that we found were not mentioned in reports from the original TEE operators.ConclusionThis study demonstrated that LASPs were more prevalent in patients with ESUS than in patients with strokes of known origin. Our results gave rise to the question of whether anticoagulation would be appropriate for some patients with ESUS. New large-scale, prospective studies should be conducted to address this issue. Additionally, considering the low rate of LASP descriptions, we concluded that the awareness of operators should be raised to improve their success in identifying LASPs.

Prevalence of left atrial septal pouch among patients with embolic stroke of undetermined source or stroke of known etiology: A retrospective study

Abstract Background and objectives Cryptogenic strokes can be defined by the criteria established for an embolic stroke of undetermined source (ESUS). Some embolic events might be caused by a left atrial septal pouch (LASP), due to the potential of thrombus formation. In this study we aimed to determine if LASP is a risk factor for ESUS when compared to a population of strokes of known origin, the LASP screening rate in our institution and if LASP dimensions influences the risk of ESUS. Methods We retrospectively analyzed transesophageal echocardiograms (TEEs) in a large cohort of patients that had experienced ischemic strokes. Two authors performed blinded, independent searches for LASPs by reviewing 1152 TEEs from patients that had experienced a stroke or transient ischemic attack. We excluded 26 TEEs, due to incorrect imaging. Next, we reviewed patient medical files. Results Among the 1126 included patients, 148 had an ESUS (ESUS+ group) and 978 had strokes of known origin (ESUS– group). A LASP was present in 176 patients, including 32 patients (21.6% of LASPs) in the ESUS+ group and 144 patients (14.7% of LASPs) in the ESUS– group. In multivariate analysis, LASP was independently associated with ESUS (P = 0,019). 61.9% of LASPs that we found were not mentioned in reports from the original TEE operators. Conclusion This study demonstrated that LASPs were more prevalent in patients with ESUS than in patients with strokes of known origin. Our results gave rise to the question of whether anticoagulation would be appropriate for some patients with ESUS. New large-scale, prospective studies should be conducted to address this issue. Additionally, considering the low rate of LASP descriptions, we concluded that the awareness of operators should be raised to improve their success in identifying LASPs.

Spectral-Clustering of Lagrangian Trajectory Graphs: Application to Abdominal Aortic Aneurysms.

Identification of coherent structures in cardiovascular flows is crucial to describe the transport and mixing of blood. Coherent structures can highlight locations where minimal blood mixing takes place, thus, potential thrombus formation can be expected thither. Graph-based approaches have recently been introduced in order to describe fluid transport and mixing between multiple Lagrangian trajectories, where each trajectory serves as a node that can be connected to another trajectory based on their relative distance during the course of time. In this study, we compute the Lagrangian trajectories from in vitro planar instantaneous velocity fields in two models of abdominal aortic aneurysms, (AAA) namely single bulge and bi-lobed. Then, we construct unweighted and undirected graphs based on the pairwise distance of Lagrangian trajectories. We report local measures of the graph namely the degree and the clustering coefficient. We also perform spectral clustering of the graph Laplacian to extract the flow coherent sets. Local graph measures reveal fluid regions of high mixing such as vortex boundaries. Through spectral clustering, the fluid is partitioned into a reduced number of coherent sets where within each set, inner mixing of fluid is maximized while the fluid mixing between different coherent sets is minimized. The approach reveals multiple coherent sets adjacent to the AAA bulge that have sustained this adjacency to the wall through their coherent motion during one cardiac cycle. Identifying coherent sets enables tracking their transport during the cardiac cycle and identify their role in the flow dynamics. Moreover, the size and the transport of the long residing coherent sets inside the AAA bulges can be deduced which may aid in predicting thrombus formation at such location.

Pathogenesis of atherosclerosis and its influence on local hemodynamics: A comparative FSI study in healthy and mildly stenosed carotid arteries

Atherosclerosis is one of the most dangerous forms of Cardiovascular disease (CVD) due to its asymptomatic nature during its early stages of development. The carotid sinus is a favorable location for plaque progression because of the temporal disturbances experienced in its environment. By performing a transient Fluid-Structure Interaction (FSI) on a healthy idealized carotid artery, zones of low Wall Shear Stress (WSS) were isolated as these regions are prone to plaque formation. A plaque was then constructed in the vicinity of these zones leading to lumen stenosis. The influence and variation of critical hemodynamic parameters such as WSS, Oscillatory Shear Index (OSI), and helicity were then analyzed in the stenosed artery, and compared to that of the healthy one. Significant variation in vessel deformation, an FSI exclusive parameter, was seen due to atherosclerotic obstruction near the bifurcation apex. Elevated WSS, OSI, and velocity levels were observed, especially around the sinus. Regions with low helical intensity corresponded to high particle residence times which originated at the sinus and developed well into the Internal Carotid Artery (ICA). All signs point to further progression of atherosclerosis, with high OSI and RRT indicating a further increase in the degrees of stenosis, or potential thrombus formation at the carotid sinus in case of plaque rupture due to increased velocity and WSS levels.

Effect of Timings of the Lavare Cycle on the Ventricular Washout in an In Vitro Flow Visualization Setup.

Left ventricular assist devices inherently alter the intraventricular flow field and create areas of blood stasis with potential thrombus formation. The Lavare cycle of the Medtronic HeartWare HVAD was designed to improve ventricular washout. This study aims to evaluate its effects on ventricular washout in a pulsatile in vitro setting with a focus on the timing of pump speed changes. Ventricular flow fields were obtained via particle image velocimetry in two modes: With constant left ventricular assist devices speed and with the Lavare cycle applied. The start of the Lavare cycle was shifted over an entire cardiac cycle, and ventricular washout was evaluated based on velocity fields, kinetic energy, and normalized pulsatility of flow fields. The ventricular flow fields showed dependence on the timing of the Lavare cycle and interaction between speed changes and the cardiac phase. Higher apical velocity was observed for speed decreases at the late E wave and for increases at mid systole by 29% (P = 0.002) and 61% (P < 0.001), respectively. Mean apical kinetic energy for these phases also increased by 21% (P = 0.0013) and 46% (P < 0.001). The Lavare cycle generally promotes higher apical washout and can specifically generate further improved washout if speed steps are applied at the correct timing on the cardiac cycle.

Influence of hemodialysis blood flow rate on the thrombogenic potential in patients with central venous catheters.

In this study we apply methods to determine the tendency for thrombus formation in different central venous catheters (CVC) models associated with flow rate variation. To calculate the thrombogenic potential, we proposed a new numerical model of the platelet lysis index (PLI) equation. To compare the results of PLI and flow rate in different models of catheters, numerical calculations were performed on three different tips of CVC. The results showed that the PLI increases as a power function of the flow rate independent of the type of CVC. This study evidenced that the higher the blood flow rate used in the catheter, the greater the potential for thrombus formation. The PLI computed at the catheter outlet presented higher values when compared to the values computed at the vein outlet indicating that the blood flow through the CVC arterial lumen presents a proportionally larger thrombogenic potential when compared to the blood flow that leaves the vein towards the atrium. This finding may have consequences for clinical practice, since there is no specific flow value recommended in the catheter when the hemodialysis machine is turned on, and with this equation it was possible to demonstrate the thrombogenic potential that the flow rate can possibly offer.

Central pontine myelinolysis during treatment of hyperglycemic hyperosmolar syndrome: a case report

BackgroundCentral pontine myelinolysis (CPM) is a non-inflammatory demyelinating lesion of the pons. CPM and extrapontine demyelination (EPM) are together termed osmotic demyelination syndrome (ODS), a known and serious complication of acute correction of hyponatremia. Conversely, hyperglycemic hyperosmolarity syndrome (HHS) develops in patients with type 2 diabetes who still have some insulin secretory ability due to infection, non-compliance with treatment, drugs, and coexisting diseases, and is often accompanied by ketosis. HHS represents a life-threatening endocrine emergency (mortality rate, 10–50%) associated with marked hyperglycemia and severe dehydration. HHS may develop ODS, and some cases have been associated with hypernatremia.Case presentationThe patient was an 87-year-old woman with hyperglycemia, dehydration, malnutrition, and potential thrombus formation during long-term bed rest. HHS was suspected to have developed due to progression of hyperglycemia and dehydration caused by pneumonia. Furthermore, ketoacidosis developed from ketosis and prerenal renal failure associated with circulating hypovolemia shock, which was also associated with disseminated intravascular coagulation. Treatment was started with continuous intravenous injection of fast-acting insulin and low-sodium replacement fluid. In addition, ceftriaxone sodium hydrate, heparin sodium, thrombomodulin α, human serum albumin, and dopamine hydrochloride were administered. Blood glucose, serum sodium, serum osmolality, and general condition (including vital, infection/inflammatory findings, and disseminated intravascular coagulation) improved promptly, but improvements in disturbance of consciousness were poor. Diffusion-weighted imaging of the brain 72 h after starting treatment showed no obvious abnormalities, but high-intensity signals in the midline of the pons became apparent 30 days later, leading to definitive diagnosis of CPM.ConclusionsFluctuation of osmotic pressure by treatment from hyperosmolarity due to hyperglycemia and hypernatremia in the presence of risk factors such as malnutrition, severe illness, and metabolic disorders may be a cause of CPM onset. When treating HHS with risk factors, the possibility of progression to ODS needs to be kept in mind.

T and Small Protrusion (TAP) vs Double-Kissing Crush Technique: Insights From In Vitro Models

BackgroundPercutaneous coronary interventions on complex bifurcation lesions may require implantation of two stents to appropriately treat diffuse side-branch (SB) disease. Comparisons among different bifurcation stenting techniques are continuously attempted by various study designs (bench tests, computer simulations, clinical studies). Among different techniques, double kissing crush (DKC) represents the last evolution for “crushing” while T and small Protrusion (TAP) represents the evolution of “T stenting”. Both techniques are actually gaining popularity, but head-to-head comparisons are lacking. Methods and resultsTwo last generation drug-eluting stents (Synergy™, Boston Scientific, MA, USA and Ultimaster™,Terumo Corp., Japan) were implanted in left main bifurcation bench models using TAP (n = 6 sets) and DKC (n = 6 sets) techniques. A peristaltic pump with fresh porcine blood was used to perfuse the blood through the silicone model at a flow rate of 200 ml/min for 4 min. Optical coherence tomography (OCT) was used to assess stent struts geometry and thrombus formation. SB cross sectional area as well as SB obstruction did not significantly differ between the two techniques. Numerical (but not statistically significant) differences were found in terms of malapposed struts (fewer with TAP) and floating struts (fewer with DKC). Thrombus formation after blood perfusion was similar between TAP and DKC technique (1.53 ± 1.12 vs. 1.20 ± 1.01 mm2, p = 0.6). ConclusionThe result of the present in-vitro study shows the absence of significant difference between TAP and DKC in terms of stent struts apposition and acute thrombus formation potential. Despite the completely different technical steps required, both techniques have similar performance according to such articulated pre-clinical evaluation. What is already known about this subject?Due to its limited complexity, T and Protrusion (TAP) technique is considered the to-go technique for bifurcation lesions with good long-term results. Recently, double kissing crush (DKC) technique has been gaining popularity and demonstrated promising results in randomized clinical trials. What does this study add?This in-vitro bench test study provides a unique detailed OCT comparison and local hemodynamic environment analysis of the two techniques. How might this impact on clinical practice?New insights of acute thrombogenicity and computational flow model simulation may guide percutaneous therapeutic strategies of bifurcation lesions.

Controllable synthesis of biomimetic nano/submicro-fibrous tubes for potential small-diameter vascular grafts.

Mimicking the morphological structure of native blood vessels is critical for the development of vascular grafts. Herein, small-diameter composite vascular grafts that integrate the nanofibrous bacterial cellulose (BC) and submicrofibrous cellulose acetate (CA) were fabricated via a combined electrospinning and step-by-step in situ biosynthesis. Scanning electron microscopy (SEM) observation shows the nano/submicro-fibrous morphology and well-interconnected porous structure of the BC/CA grafts. It is found that the BC/CA graft with a suitable BC content demonstrates lower potential of thrombus formation and enhanced endothelialization as compared to the BC and CA counterparts. Western blotting and RT-qPCR results suggest that the BC/CA-2 graft promotes endothelialization by improving expressions of genes vWF-1 and CD31 and protein CD31. The in vivo tests demonstrate much lower inflammatory response to the BC/CA graft. These results suggest that the BC/CA graft shows a great potential as an artificial graft for rapid formation of an endothelial cell monolayer.

Haemodynamics of Different Configurations of a Left Subclavian Artery Stent Graft for Thoracic Endovascular Aortic Repair

Branched stent grafts represent a viable option for left subclavian artery (LSA) revascularisation in patients treated by thoracic endovascular aortic repair (TEVAR) for Zone 2 lesions. This study investigated the haemodynamic performance of different LSA branched stent graft configurations as potential determinants of thrombotic and stroke risks. A three dimensional aortic arch geometry extracted from post-operative computed tomography images of a TEVAR patient using a single LSA branched aortic endograft was modified in silico to obtain ten potential LSA branched stent graft configurations: five down facing (0-5 - 10mm aortic protrusion with 10-12mm internal diameter), four curved (30-60° with antegrade/retrograde orientation), and one LSA orifice misalignment. The 0mm down facing stent graft was considered base configuration. Computational fluid dynamic analyses were performed to identify differences in pressure, energy, and wall shear stress (WSS) based parameters. Total pressure drop and energy loss variations among configurations were not greater than 5mmHg (6% of mean arterial pressure) and 5.7mW (0.7% of cardiac power), respectively. Protrusions up to 5mm created clinically insignificant flow disturbances. However, stent graft protrusions further into the aortic lumen created more complex haemodynamics, characterised by larger energy loss and more prominent flow recirculation. Protrusion greater than 5mm into the lumen was associated with larger areas of elevated maximum WSS (>20Pa) along the outer surface of the branched stent graft. Arterial haemodynamic characteristics are affected by LSA branched stent graft configurations, with pressure drops and energy losses likely to be clinically insignificant. The length of the stent graft protrusion into the aortic lumen generated the largest haemodynamic variations in the aortic system. Protrusions up to 5mm have smaller risk of potential thrombus generation. Conversely, larger protrusions into the aortic lumen showed more disturbed haemodynamics, suggesting a greater risk of potential thrombus formation, which may be clinically important over time.

Hemodynamic analysis of a novel stent graft design with slit perforations in thoracic aortic aneurysm

Thoracic endovascular aortic repair (TEVAR) has been introduced as a less invasive approach to the treatment of thoracic aortic aneurysm (TAA). However, the effectiveness of TEVAR in the treatment of TAA is often limited due to the complex anatomy of aortic arch. Flow preservation at the three supra-aortic branches further increases the overall technical difficulty. This study proposes a novel stent graft design with slit perforations that can positively alter the hemodynamics at the aortic arch while maintaining blood flow to supra-aortic branches. We carried out a computational fluid dynamic (CFD) analysis to evaluate flow characteristics near stented aortic arch in simplified TAA models, followed by in-vitro experiments using particle image velocimetry (PIV) in a mock circulatory loop. The hemodynamics result was studied in terms of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and endothelial cell action potential (ECAP). The results showed that the stent graft with slit perforations can reduce the disturbed flow region considerably. Furthermore, the effect of the slits on flow preservation to the supra-aortic branches was simulated and compared with experimental results. The effectiveness of the stent graft with slit perforations in preserving flow to the branches was demonstrated by both simulated and experimental results. Low TAWSS and elevated ECAP were observed in the aortic arch aneurysm after the placement of the stent graft with slits, implying the potential of thrombus formation in the aneurysm. On the other hand, the effects of the stent grafts with full-slit design and half-slit design on the shear stress did not differ significantly. The present analysis indicated that not only could the stent graft with slit perforations shield the aneurysm from rupture, but also it resulted in a favorable environment for thrombus that can contribute to the shrinkage of the aneurysm.

Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal Thrombus

Over 75% of abdominal aortic aneurysms harbor an intraluminal thrombus, and increasing evidence suggests that biologically active thrombus contributes to the natural history of these potentially lethal lesions. Thrombus formation depends on the local hemodynamics, which in turn depends on morphological features of the aneurysm and near vasculature. We previously presented a hemodynamically motivated “thrombus formation potential” that predicts where and when thrombus might form. Herein, we combine detailed studies of the three-dimensional hemodynamics with methods of sparse grid collocation and interpolation via kriging to examine roles of five key morphological features of aneurysms on thrombus formation: lesion diameter, axial position, length, curvature, and renal artery position. Computational simulations suggest that maximum diameter is a key determinant of thrombogenicity, but other morphological features modulate this dependence. More distally located lesions tend to have a higher thrombus formation potential and shorter lesions tend to have a higher potential than longer lesions, given the same aneurysmal dilatation. Finally, movement of vortical structures through the infrarenal aorta and lesion can significantly affect thrombogenicity. Formation of intraluminal thrombus within an evolving abdominal aortic aneurysm thus depends on coupled morphological features, not all intuitive, and computational simulations can be useful for predicting thrombogenesis.