In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics: In silico analysis of femoro-jugular VV ECMO.

BACKGROUND: Increasingly, computational fluid dynamics (CFD) is helping explore the impact of variables like: cannula design/size/position/flow rate and patient physiology on venovenous (VV) extracorporeal membrane oxygenation (ECMO). Here we use a CFD model to determine what role cardiac output (CO) plays and to analyse return cannula dynamics. METHODS: Using a patient-averaged model of the right atrium and venae cava, we virtually inserted a 19Fr return cannula and a 25Fr drainage cannula. Running large eddy simulations, we assessed cardiac output at: 3.5-6.5 L/min and ECMO flow rate at: 2-6 L/min. We analysed recirculation fraction (Rf), time-averaged wall shear stress (TAWSS), pressure, velocity, and turbulent kinetic energy (TKE) and extracorporeal flow fraction (EFF = ECMO flow rate/CO). RESULTS: Increased ECMO flow rate and decreased CO (high EFF) led to increased Rf (R = 0.98, log fit). Negative pressures developed in the venae cavae at low CO and high ECMO flow (high CR). Mean return cannula TAWSS was >10 Pa for all ECMO flow rates, with majority of the flow exiting the tip (94.0-95.8 %). CONCLUSIONS: Our results underpin the strong impact of CO on VV ECMO. A simple metric like EFF, once supported by clinical data, might help predict Rf for a patient at a given ECMO flow rate. The return cannula imparts high shear stresses on the blood, largely a result of the internal diameter.

Modelling large scale artery haemodynamics from the heart to the eye in response to simulated microgravity.

We investigated variations in haemodynamics in response to simulated microgravity across a semi-subject-specific three-dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth gravity case and a simulated microgravity case. Under simulated microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates that 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data-specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to simulated microgravity, relative to an upright position in Earth gravity.

Hemodynamic Implications of STABILISE Technique for Aortic Dissection Repair.

BACKGROUND: The stent-assisted balloon-induced intimal disruption and relamination (STABILISE) technique for treatment of type B dissection has shown promising clinical results at mid-term. Computational modeling is a way of noninvasively obtaining hemodynamic effects, such as pressure and wall shear stress, leading to a better understanding of potential benefits. Particular areas of interest are (1) the effect of intimal disruption and re-lamination and (2) the effect of the bare metal stent in the visceral aortic segment. METHODS: Single-center prospective case series. Data from 5 consecutive locally performed cases of STABILISE technique were analyzed. Included cases were type B aortic dissection with or without prior de-branching. The STABILISE procedure had to be performed without 30-day major complications. Preoperative and postoperative imaging data for each patient were transferred to the biomedical engineering team. Each case was reconstructed, meshed, and simulated with computational fluid dynamics using patient-specific data (heart rate, blood pressure, height, and weight). Hemodynamic parameters were then extracted from the simulations. RESULTS: In all cases, computational analysis showed for postoperative patients: (1) a drop in pressure difference between lumina and (2) lower wall shear stress effects, compared to their preoperative status. These observations were most pronounced in the visceral aortic segment. CONCLUSIONS: Computational modeling shows favourable changes in the flow dynamics of type B dissection treated using the STABILISE technique. This may suggest protective effects of this technique for long-term aortic healing and cicatrization.

Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation (ECMO) can be performed with two single lumen cannulas (SLCs) or one dual-lumen cannula (DLC) where low recirculation fraction ([Formula: see text]) is a key performance criterion. DLCs are widely believed to have lower [Formula: see text], though these have not been directly compared. Similarly, correct positioning is considered critical although its impact is unclear. We aimed to compare two common bi-caval DLC designs and quantify [Formula: see text] in several positions. Two different commercially available DLCs were sectioned, measured, reconstructed, scaled to 27Fr and simulated in our previously published patient-averaged computational model of the right atrium (RA) and venae cavae at 2-6 L/min. One DLC was then used to simulate ± 30° and ± 60° rotation and ± 4 cm insertion depth. Both designs had low [Formula: see text] (< 7%) and similar SVC/IVC drainage fractions and pressure drops. Both cannula reinfusion ports created a high-velocity jet and high shear stresses in the cannula (> 413 Pa) and RA (> 52 Pa) even at low flow rates. Caval pressures were abnormally high (16.2-23.9 mmHg) at low flow rates. Rotation did not significantly impact [Formula: see text]. Short insertion depth increased [Formula: see text] (> 31%) for all flow rates whilst long insertion only increased [Formula: see text] at 6 L/min (24%). Our results show that DLCs have lower [Formula: see text] compared to SLCs at moderate-high flow rates (> 4 L/min), but high shear stresses. Obstruction from DLCs increases caval pressures at low flow rates, a potential reason for increased intracranial hemorrhages. Cannula rotation does not impact [Formula: see text] though correct insertion depth is critical.

Cannulation configuration and recirculation in venovenous extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation is a treatment for acute respiratory distress syndrome. Femoro-atrial cannulation means blood is drained from the inferior vena cava and returned to the superior vena cava; the opposite is termed atrio-femoral. Clinical data comparing these two methods is scarce and conflicting. Using computational fluid dynamics, we aim to compare atrio-femoral and femoro-atrial cannulation to assess the impact on recirculation fraction, under ideal conditions and several clinical scenarios. Using a patient-averaged model of the venae cavae and right atrium, commercially-available cannulae were positioned in each configuration. Additionally, occlusion of the femoro-atrial drainage cannula side-holes with/without reduced inferior vena cava inflow (0-75%) and retraction of the atrio-femoral drainage cannula were modelled. Large-eddy simulations were run for 2-6L/min circuit flow, obtaining time-averaged flow data. The model showed good agreement with clinical atrio-femoral recirculation data. Under ideal conditions, atrio-femoral yielded 13.5% higher recirculation than femoro-atrial across all circuit flow rates. Atrio-femoral right atrium flow patterns resembled normal physiology with a single large vortex. Femoro-atrial cannulation resulted in multiple vortices and increased turbulent kinetic energy at > 3L/min circuit flow. Occluding femoro-atrial drainage cannula side-holes and reducing inferior vena cava inflow increased mean recirculation by 11% and 32%, respectively. Retracting the atrio-femoral drainage cannula did not affect recirculation. These results suggest that, depending on drainage issues, either atrio-femoral or femoro-atrial cannulation may be preferrable. Rather than cannula tip proximity, the supply of available venous blood at the drainage site appears to be the strongest factor affecting recirculation.

Impact of altered vena cava flow rates on right atrium flow characteristics.

The right atrium (RA) combines the superior vena cava (SVC) and inferior vena cava (IVC) flows. Treatments like extracorporeal membrane oxygenation (ECMO) and hemodialysis by catheter alter IVC/SVC flows. Here we assess how altered IVC/SVC flow contributions impact RA flow. Four healthy volunteers were imaged with computerized tomography (CT), reconstructed and combined into a patient-averaged model. Large eddy simulations (LESs) were performed for a range of IVC/SVC flow contributions (30%-70% each, increments of 5%) and common flow metrics were recorded. Model sensitivity to reconstruction domain extent, constant/pulsatile inlets, and hematocrit was also assessed. Consistent with literature, a single vortex occupied the central RA across all flowrates with a smaller counter-rotating vortex, not previously reported, in the auricle. Vena cava flow was highly helical. RA turbulent kinetic energy (TKE; P = 0.027) and time-averaged wall shear stress (WSS; P < 0.001) increased with SVC flow. WSS was lower in the auricle (2 Pa, P < 0.001). WSS in the vena cava was equal at IVC/SVC = 65/35%. The model was highly sensitive to the reconstruction domain with cropped geometries lacking helicity in the venae cavae, altering the RA flow. The RA flow was not significantly affected by constant inlets or hematocrit. The commonly reported vortex in in the central RA is confirmed; however, a new, smaller vortex was also recorded in the auricle. When IVC flow dominates, as is normal, TKE in the RA is reduced and WSS in the venae cavae equalize. Significant helicity exists in the vena cava, as a result of distal geometry and this geometry appears crucial to accurately simulating RA flow.NEW & NOTEWORTHY Right atrium turbulent kinetic energy increases as the proportion of flow entering from the superior vena cava is increased. Although the commonly reported large right atrium vortex was confirmed across all flow scenarios, a new smaller vortex is observed in the right auricle. The caval veins exhibit highly helical flow and this appears to be the result of distal venous morphology.

Proximal false lumen thrombosis is associated with low false lumen pressure and fewer complications in type B aortic dissection.

BACKGROUND: Improved risk stratification is a key priority for type B aortic dissection (TBAD). Partial false lumen thrombus morphology is an emerging predictor of complications. However, partial thrombosis is poorly defined, and its evaluation in clinical studies has been inconsistent. Thus, we aimed to characterize the hemodynamic pressure in TBAD and determine how the pressure relates to the false lumen thrombus morphology and clinical events. METHODS: The retrospective admission computed tomography angiograms of 69 patients with acute TBAD were used to construct three-dimensional computational models for simulation of cyclical blood flow and calculation of pressure. The patients were categorized by the false lumen thrombus morphology as minimal, extensive, proximal or distal thrombosis. Linear regression analysis was used to compare the luminal pressure difference between the true and false lumen for each morphology group. The effect of morphology classification on the incidence of acute complications within 14 days was studied using logistic regression adjusted for clinical parameters. A survival analysis for adverse aortic events at 1 year was also performed using Cox regression. RESULTS: Of the 69 patients, 44 had experienced acute complications and 45 had had an adverse aortic event at 1 year. The mean ± standard deviation age was 62.6 ± 12.6 years, and 75.4% were men. Compared with the patients with minimal thrombosis, those with proximal thrombosis had a reduced false lumen pressure by 10.1 mm Hg (95% confidence interval [CI], 4.3-15.9 mm Hg; P = .001). The patients who had not experienced an acute complication had had a reduced relative false lumen pressure (-6.35 mm Hg vs -0.62 mm Hg; P = .03). Proximal thrombosis was associated with fewer acute complications (odds ratio, 0.17; 95% CI, 0.04-0.60; P = .01) and 1-year adverse aortic events (hazard ratio, 0.36; 95% CI, 0.16-0.80; P = .01). CONCLUSIONS: We found that proximal false lumen thrombosis was a marker of reduced false lumen pressure. This might explain how proximal false lumen thrombosis appears to be protective of acute complications (eg, refractory hypertension or pain, aortic rupture, visceral or limb malperfusion, acute expansion) and adverse aortic events within the first year.

Surgical Decision Making in Uncomplicated Type B Aortic Dissection: A Survey of Australian/New Zealand and European Surgeons.

OBJECTIVE: There is controversy about the role of pre-emptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD). The aim was to understand expert opinions and the factors influencing decision making. METHODS: In 2018, surgeons from Australia/New Zealand (ANZ) and Europe (EUR) were contacted to participate in an online survey which comprised questions about preferences for pre-emptive TEVAR, followed by five case scenarios, and two ranking questions for anatomical and technical risk factors respectively. Case 1 was designed to favour TEVAR in a hypertensive patient with partial false lumen thrombosis and large diameter (aortic ≥ 40 mm, false lumen ≥ 22 mm). Case 2 had no risk factors mandating TEVAR, according to current evidence. Cases 3, 4, and 5 were designed to test one risk factor respectively, large entry tear on the inner aortic curvature (≥10 mm), partial false lumen thrombosis, and large diameter alone. RESULTS: There were 75 responses, 42 from EUR and 33 from ANZ. Almost half of surgeons (49.3%) endorsed pre-emptive TEVAR with 82.3% preferring to perform TEVAR in the subacute phase. In Case 1 and 5, 58.3% and 52.8% of surgeons respectively chose TEVAR, the highest rates obtained in the survey. Cases 1 and 5 included large diameters ≥40 mm, which were ranked the highest in importance when surgeons considered anatomical risk factors. Surgeons who recommend pre-emptive TEVAR were more likely to choose TEVAR in both Case 1 (83.3% vs. 33.3%, p < .001, 95% CI 27.6%-65.8%) and Case 5 (69.4% vs. 38.2%, p = .008, 95% CI 8.2%-50.0%). CONCLUSION: In this survey about uncomplicated TBAD, about half of surgeons recommended pre-emptive TEVAR in selected cases. The surgeon's predisposition towards intervention and large diameters appear to be the most influential factors in decision making. These findings underline the uncertainty in today's practice and emphasise the need for better predictive tools.

Morphology and Computational Fluid Dynamics Support a Novel Classification of Common Iliac Aneurysms.

OBJECTIVE: Isolated common iliac artery aneurysms (CIAAs) are uncommon, and evidence concerning their development, progression, and management is weak. The objective was to describe the morphology and haemodynamics of isolated CIAAs in a retrospective study. METHODS: Initially, a series of 25 isolated CIAAs (15 intact, 10 ruptured) in 23 patients were gathered from multiple centres, reconstructed from computed tomography, and then morphologically classified and analysed with computational fluid dynamics. The morphological classification was applied in a separate, consecutive cohort of 162 patients assessed for elective aorto-iliac intervention, in which 55 patients had intact CIAAs. RESULTS: In the isolated CIAA cohort, three distinct morphologies were identified: complex (involving a bifurcation); fusiform; and kinked (distal to a sharp bend in the CIA), with mean diameters of 90.3, 48.3, and 31.7 mm, and mean time averaged wall shear stresses of 0.16, 0.31, and 0.71 Pa, respectively (both analysis of variance p values < .001). Kinked cases vs. fusiform cases had less thrombus and favourable haemodynamics similar to the non-aneurysmal contralateral common iliac artery (CIA). Ruptured isolated CIAAs were large (mean diameter 87.5 mm, range 55.5-138.0 mm) and predominantly complex. The mean CIA length for aneurysmal arteries was greatest in kinked cases followed by complex and fusiform (100.8 mm, 91.1 mm, and 80.6 mm, respectively). The morphological classification was readily applicable to a separate elective patient cohort. CONCLUSION: A new morphological categorisation of CIAAs is proposed. Potentially this is associated with both haemodynamics and clinical course. Further research is required to determine whether the kinked CIAA is protected haemodynamically from aneurysm progression and to establish the wider applicability of the categorisation presented.

The application of computational modeling for risk prediction in type B aortic dissection.

OBJECTIVE: New tools are urgently needed to help with surgical decision-making in type B aortic dissection (TBAD) that is uncomplicated at the time of initial presentation. This narrative review aims to answer the clinical question, Can computational modeling be used to predict risk in acute and chronic Stanford TBAD? METHODS: The review (PROSPERO 2018 CRD42018104472) focused on risk prediction in TBAD. A comprehensive search of the Ovid MEDLINE database, using terms related to computational modeling and aortic dissection, was conducted to find studies of any form published between 1998 and 2018. Cohort studies, case series, and case reports of adults (older than 18 years) with computed tomography or magnetic resonance imaging diagnosis of TBAD were included. Computational modeling was applied in all selected studies. RESULTS: There were 37 studies about computational modeling of TBAD identified from the search, and the findings were synthesized into a narrative review. Computational modeling can produce numerically calculated values of stresses, pressures, and flow velocities that are difficult to measure in vivo. Hemodynamic parameters-high or low wall shear stress, high pressure gradient between lumens during the cardiac cycle, and high false lumen flow rate-have been linked to the pathogenesis of branch malperfusion and aneurysm formation by numerous studies. Considering the major outcomes of end-organ failure, aortic rupture, and stabilization and remodeling, hypotheses have been generated about inter-relationships of measurable parameters in computational models with observable anatomic and pathologic changes, resulting in specific clinical outcomes. CONCLUSIONS: There is consistency in study findings about computational modeling in TBAD, although a limited number of patients have been analyzed using various techniques. The mechanistic patterns of association found in this narrative review should be investigated in larger cohort prospective studies to further refine our understanding. It highlights the importance of patient-specific computational hemodynamic parameters in clinical decision-making algorithms. The current challenge is to develop and to test a risk assessment method that can be used by clinicians for TBAD.

A computational framework to investigate retinal haemodynamics and tissue stress.

The process of vision begins in the retina, yet the role of biomechanical forces in the retina is relatively unknown and only recently being explored. This contribution describes a computational framework involving 3D fluid-structure interaction simulations derived from fundus images that work towards creating unique data on retinal biomechanics. We developed methods to convert 2D fundus photographs into 3D geometries that follow the curvature of the retina. Retina arterioles are embedded into a six-layer representation of the retinal tissue with varying material properties throughout the retinal tissue. Using three different human retinas (healthy, glaucoma, diabetic retinopathy) and by varying our simulation approaches, we report the effects of transient versus steady flow, viscosity assumptions (Newtonian, non-Newtonian and Fåhræus-Lindqvist effect) and rigid versus compliant retinal tissue, on resulting wall shear stress (WSS) and von Mises stress. In the retinal arterioles, the choice of viscosity model is important and WSS obtained from models with the Fåhræus-Lindqvist effect is markedly different from Newtonian and non-Newtonian models. We found little difference in WSS between steady-state and pulsatile simulations (< 5%) and show that WSS varies by about 7% between rigid and deformable models. Comparing the three geometries, we found notably different WSS in the healthy (3.3 ± 1.3 Pa), glaucoma (5.7 ± 1.6 Pa) and diabetic retinopathy cases (4.3 ± 1.1 Pa). Conversely, von Mises stress was similar in each case. We have reported a novel biomechanical framework to explore the stresses in the retina. Despite current limitations and lack of complete subject-specific physiological inputs, we believe our framework is the first of its kind and with further improvements could be useful to better understand the biomechanics of the retina.

Morphology and Hemodynamics in Isolated Common Iliac Artery Aneurysms Impacts Proximal Aortic Remodeling.

Objective- Isolated common iliac artery aneurysms (CIAA) are rare. Their prognosis and influence on aortoiliac blood flow and remodeling are unclear. We evaluated the hypotheses that morphology at and distal to the aortic bifurcation, together with the associated hemodynamic changes, influence both the natural history of CIAA and proximal aortic remodeling. Approach and Results- Twenty-five isolated CIAAs (15 intact, 10 ruptured), in 23 patients were reconstructed and analyzed with computational fluid dynamics: all showed abnormal flow. Then we studied a series of 24 hypothetical aortoiliac geometries in silico with varying abdominal aortic deflection and aortic bifurcation angles: key findings were assessed in an independent validation cohort of 162 patients. Wall shear stress in isolated unilateral CIAAs was lower than the contralateral common iliac artery, 0.38±0.33 Pa versus 0.61±0.24 Pa, inversely associated with CIAA diameter ( P<0.001) and morphology (high shear stress in variants distal to a sharp kink). Rupture usually occurred in regions of elevated low and oscillatory shear with a wide aortic bifurcation angle. Abdominal aortas deflected towards the CIAA for most unilateral isolated CIAAs (14/21). In silico, wider bifurcation angles created high focal regions of low and oscillatory shear in the common iliac artery. The associations of unilateral CIAA with aortic deflection and common iliac artery diameter with bifurcation angle were confirmed in the validation cohort. Conclusions- Decreasing wall shear stress is strongly associated with CIAA progression (larger aneurysms and rupture), whereas abnormal blood flow in the CIAA seems to promote proximal aortic remodeling, with adaptive lateral deflection of the abdominal aorta towards the aneurysmal side.

Haemodynamics and stresses in abdominal aortic aneurysms: A fluid-structure interaction study into the effect of proximal neck and iliac bifurcation angle.

Our knowledge of how geometry influences abdominal aortic aneurysm (AAA) biomechanics is still developing. Both iliac bifurcation angle and proximal neck angle could impact the haemodynamics and stresses within AAA. Recent comparisons of the morphology of ruptured and intact AAA show that cases with large iliac bifurcation angles are less likely to rupture than those with smaller angles. We aimed to perform fluid-structure interaction (FSI) simulations on a range of idealised AAA geometries to conclusively determine the influence of proximal neck and iliac bifurcation angle on AAA wall stress and haemodynamics. Peak wall shear stress (WSS) and time-averaged WSS (TAWSS) in the AAA sac region only increased when the proximal neck angle exceeded 30°. Both peak WSS (p<0.0001) and peak von Mises wall stress (p=0.027) increased with iliac bifurcation angle, whereas endothelial cell activation potential (ECAP) decreased with iliac bifurcation angle (p<0.001) and increased with increasing neck angle. These observations may be important as AAAs have been shown to expand, develop thrombus and rupture in areas of low WSS. Here we show that AAAs with larger iliac bifurcation angles have higher WSS, potentially reducing the likelihood of rupture. Furthermore, ECAP was lower in AAA geometries with larger iliac bifurcation angles, implying less likelihood of thrombus development and wall degeneration. Therefore our findings could help explain the clinical observation of lower rupture rates associated with AAAs with large iliac bifurcation angles.