In silico model development and optimization of in vitro lung cell population growth.

Tissue engineering predominantly relies on trial and error in vitro and ex vivo experiments to develop protocols and bioreactors to generate functional tissues. As an alternative, in silico methods have the potential to significantly reduce the timelines and costs of experimental programs for tissue engineering. In this paper, we propose a methodology to formulate, select, calibrate, and test mathematical models to predict cell population growth as a function of the biochemical environment and to design optimal experimental protocols for model inference of in silico model parameters. We systematically combine methods from the experimental design, mathematical statistics, and optimization literature to develop unique and explainable mathematical models for cell population dynamics. The proposed methodology is applied to the development of this first published model for a population of the airway-relevant bronchio-alveolar epithelial (BEAS-2B) cell line as a function of the concentration of metabolic-related biochemical substrates. The resulting model is a system of ordinary differential equations that predict the temporal dynamics of BEAS-2B cell populations as a function of the initial seeded cell population and the glucose, oxygen, and lactate concentrations in the growth media, using seven parameters rigorously inferred from optimally designed in vitro experiments.

Bilayer and Trilayer C3N/Blue-Phosphorene Heterostructures as Potential Anode Materials for Potassium-Ion Batteries.

Two-dimensional (2D) van der Waals heterostructures outperform conventional anode materials for postlithium-ion batteries in terms of mechanical, thermal, and electrochemical properties. This study systemically investigates the performance of bilayer and trilayer C3N/blue phosphorene (C3N/BlueP) heterostructures as anode materials for potassium-ion batteries (KIBs) using first-principles density functional theory calculations. This study reveals that the adsorption and diffusion of K ions on bilayer and trilayer C3N/BlueP heterostructures are markedly superior to those of their monolayer counterparts. A bilayer heterostructure (C3N/BlueP) effectively reduces the bandgap of the BlueP monolayer (1.98 eV) to 0.02 eV, whereas trilayer heterostructures (bilayer-C3N/BlueP and C3N/bilayer-BlueP) exhibit metallic behavior with no bandgap. Additionally, the theoretical capacity of the bilayer and trilayer heterostructures ranges from 636.7 to 755.5 mA h g-1, considerably higher than the theoretical capacity of other prospective 2D heterostructures for KIBs investigated in the literature. This study also shows that the heterostructures exhibit K-ion diffusion barriers as low as 0.042 eV, ensuring the relatively fast diffusion of K ions.

Nonlinear dependence (on ionic strength, pH) of surface charge density and zeta potential in microchannel electrokinetic flow.

In this work, a numerical method is proposed to predict the electrokinetic phenomena and combined with an experimental study of the surface charge density (ρs) and zeta potential (ζ) behavior is investigated for borosilicate immersed in KCl and NaCl electrolytes, and for imogolite immersed in KCl, CaCl2, and MgCl2 electrolytes. Simulations and experiments of the electrokinetic flows with electrolyte solutions were performed to accurately determine the electric double layer (EDL), ζ, and ρs at various electrolyte concentrations and pH. The zeta potential was experimentally determined and numerically predicted by solving the coupled governing equations of mass, species, momentum, and electrical field iteratively. Our numerical prediction shows that ζ for borosilicate develops strong nonlinear behavior with the ion concentration following a power-law. Likewise, the ρs obeys a nonlinear behavior, decreasing as the concentration increases. Moreover, for imogolite, both ζ and the ρs behave nonlinearly with the pH. The EDL for borosilicate and imogolite becomes thinner as the electrolyte concentration and pH increase; this behavior is caused by increased ρs, resulting in the higher attraction of the free charges. The reported nonlinear behavior describes more accurately the interaction of the nanoparticle surface charge with the electrolytes and its effect on the electrolyte transport properties.

Prediction of bird-beak configuration in thoracic endovascular aortic repair preoperatively using patient-specific finite element simulations.

Objectives: Formation of bird-beak configuration in thoracic endovascular aortic repair (TEVAR) has been shown to be correlated with the risk of complications such as type Ia endoleaks, stent graft migration, and collapse. The aim of this study was to use patient-specific computational simulations of TEVAR to predict the formation of bird-beak configuration preoperatively. Methods: Patient-specific TEVAR computational simulations are developed using a retrospective cohort of patients treated for thoracic aortic aneurysm. The preoperative computed tomography images were segmented to develop three-dimensional geometry of the thoracic aorta. These geometries were used in finite element simulations of stent graft deployment during TEVAR. Simulated results were compared against the postoperative computed tomography images to assess the accuracy of simulations in predicting the proximal position of a deployed stent graft and presence of bird-beak. In cases with a bird-beak configuration, the length and angle of the bird-beak were measured and compared between the simulated and postoperative results. Results: Twelve TEVAR patient cases were simulated. Computational simulations were able to accurately predict whether the proximal stent graft was fully apposed, proximal bare stents were protruded, or bird-beak configuration was present. In three cases with bird-beak configuration, simulations predicted the length and angle of the bird-beak with less than 10% and 24% error, respectively. Other factors such as a small aortic arch angle, small oversizing value, and landing zones close to the arch apex may have played a role in formation of bird-beak in these patients. Conclusions: Computational simulations of TEVAR accurately predicted the proximal position of a deployed stent graft and the presence of bird-beak preoperatively. The computational models were able to predict the length and angle of bird-beak configurations with good accuracy. These simulations can provide insight into the surgical planning process with the goal of minimizing bird-beak occurrence.

A Comparison of Vessel Patch Materials in Tetralogy of Fallot Patients Using Virtual Surgery Techniques.

Tetralogy of Fallot (ToF) is characterized by stenosis causing partial obstruction of the right ventricular outflow tract, typically alleviated through the surgical application of a vessel patch made from a biocompatible material. In this study, we use computational simulations to compare the mechanical performance of four patch materials for various stenosis locations. Nine idealized pre-operative ToF geometries were created by imposing symmetrical stenoses on each of three anatomical sub-regions of the pulmonary arteries of three patients with previously repaired ToF. A virtual surgery methodology was implemented to replicate the steps of vessel de-pressurization, surgical patching, and subsequent vessel expansion after reperfusion. Significant differences in patch average stress (p < 0.001) were found between patch materials. Biological patch materials (porcine xenopericardium, human pericardium) exhibited higher patch stresses in comparison to synthetic patch materials (Dacron and PTFE). Observed differences were consistent across the various stenosis locations and were insensitive to patient anatomy.

A modeling framework for computational simulations of thoracic endovascular aortic repair.

Thoracic endovascular aortic repair (TEVAR) is a minimally invasive treatment for thoracic aortic conditions including aneurysms and is associated with a number of postoperative stent graft related complications. Computational simulations of TEVAR have the potential to predict surgical outcomes and complications preoperatively. When using simulations for stent graft design and prediction of complications in a population, it is difficult to generalize patient-specific TEVAR computational models due to patient variability. This study proposes a novel modeling framework for creating realistic population-based computational models of TEVAR focused on aneurysms that allow for developing various clinically relevant geometric configurations and scenarios that are not easily attainable with limited patient data. The framework includes a methodology for developing population-based thoracic aortic geometries and defining age-dependent aortic tissue material models, as well as detailed steps and boundary conditions for finite element modeling of stent graft deployment during TEVAR. The simulation framework is illustrated for predicting the formation of a bird-beak configuration, a wedge-shaped gap at the proximal end of the deployed stent graft in TEVAR that leads to incomplete seal. A baseline TEVAR simulation model was developed along with three simulations in which the value of aortic curvature, aortic arch angle, or aortic tissue properties varied from the baseline model. Analyzing the length and angle of the bird-beak configuration in each case shows that the bird-beak size is sensitive to different values of the aortic geometry highlighting the importance of using realistic parameter values.

Identification of geometric and mechanical factors predictive of bird-beak configuration in thoracic endovascular aortic repair using computational models of stent graft deployment.

Objective: Formation of a bird-beak configuration in thoracic endovascular aortic repair (TEVAR) has been shown to be influenced by various factors. However, the main cause of bird-beak formation remains poorly understood. The hypothesis has been that the geometric and mechanical properties of both the aorta and the stent graft contribute to the formation and extent of a bird-beak configuration. The goal of the present study was to use parameter-based computational simulations of TEVAR to predict for bird-beak formation and identify its most significant contributing factors. Methods: In the present study, we considered five parameters for the computational simulations of TEVAR, including aortic curvature, aortic arch angle, age as a surrogate for thoracic aortic tissue properties, TEVAR landing zone, and stent graft oversizing. Using an experimental design approach, computational models for 160 TEVAR scenarios were developed by varying the values of the simulation parameters within clinically relevant ranges. The bird-beak length and angle were used as metrics to evaluate the simulation results. Statistical analysis of the simulation data using a random forest model was conducted to identify significant parameters and interactions. Results: The mean ± standard deviation of the bird-beak length and angle across 160 simulations were 4.32 ± 4.87 mm and 9.16° ± 12.21°, respectively. The largest mean bird-beak length and angle were found in the most distal location in zone 0 (10.04 mm) and zone 2 (21.48°), respectively. An inverse correlation was found between the aortic arch angle and the bird-beak length and angle. In ∼75% of the scenarios, increased stent graft oversizing either fully resolved the presence of the bird-beak configuration or had reduced its size. In the remaining 25%, oversizing minimally changed the bird-beak length and enlarged the bird-beak angle, which mainly occurred in cases with a smaller aortic arch angle and landing zones near the arch apex. This was justified by the mechanism of stent graft bending in the arch angulation. The aortic curvature and tissue properties were shown to be statistically insignificant in relation to bird-beak formation. Conclusions: Significant parameters predictive of a bird-beak configuration in TEVAR were identified, and the trends in which each parameter influenced the bird-beak size were determined. The findings from the present study can inform the surgical planning and device selection process with the goal of minimizing bird-beak formation.

Cell Inertia: Predicting Cell Distributions in Lung Vasculature to Optimize Re-endothelialization.

We created a transient computational fluid dynamics model featuring a particle deposition probability function that incorporates inertia to quantify the transport and deposition of cells in mouse lung vasculature for the re-endothelialization of the acellular organ. Our novel inertial algorithm demonstrated a 73% reduction in cell seeding efficiency error compared to two established particle deposition algorithms when validated with experiments based on common clinical practices. We enhanced the uniformity of cell distributions in the lung vasculature by increasing the injection flow rate from 3.81 ml/min to 9.40 ml/min. As a result, the cell seeding efficiency increased in both the numerical and experimental results by 42 and 66%, respectively.

Ascending aortic aneurysm haemodynamics are associated with aortic wall biomechanical properties.

OBJECTIVES: The effect of aortic haemodynamics on arterial wall properties in ascending thoracic aortic aneurysms (ATAAs) is not well understood. We aim to delineate the relationship between shear forces along the aortic wall and loco-regional biomechanical properties associated with the risk of aortic dissection. METHODS: Five patients with ATAA underwent preoperative magnetic resonance angiogram and four-dimensional magnetic resonance imaging. From these scans, haemodynamic models were constructed to estimate maximum wall shear stress (WSS), maximum time-averaged WSS, average oscillating shear index and average relative residence time. Fourteen resected aortic samples from these patients underwent bi-axial tensile testing to determine energy loss (ΔUL) and elastic modulus (E10) in the longitudinal (ΔULlong, E10long) and circumferential (ΔULcirc, E10circ) directions and the anisotropic index (AI) for each parameter. Nine resected aortic samples underwent peel testing to determine the delamination strength (Sd). Haemodynamic indices were then correlated to the biomechanical properties. RESULTS: A positive correlation was found between maximum WSS and ΔULlong rs=0.75, P = 0.002 and AIΔUL (rs=0.68, P=0.01). Increasing maximum time-averaged WSS was found to be associated with increasing ΔULlong (rs=0.73, P = 0.003) and AIΔUL (rs=0.62, P=0.02). Average oscillating shear index positively correlated with Sd (rs=0.73,P=0.04). No significant relationship was found between any haemodynamic index and E10, or between relative residence time and any biomechanical property. CONCLUSIONS: Shear forces at the wall of ATAAs are associated with local degradation of arterial wall viscoelastic hysteresis (ΔUL) and delamination strength, a surrogate for aortic dissection. Haemodynamic indices may provide insights into aortic wall integrity, ultimately leading to novel metrics for assessing risks associated with ATAAs.

Vessel network extraction and analysis of mouse pulmonary vasculature via X-ray micro-computed tomographic imaging.

In this work, non-invasive high-spatial resolution three-dimensional (3D) X-ray micro-computed tomography (µCT) of healthy mouse lung vasculature is performed. Methodologies are presented for filtering, segmenting, and skeletonizing the collected 3D images. Novel methods for the removal of spurious branch artefacts from the skeletonized 3D image are introduced, and these novel methods involve a combination of distance transform gradients, diameter-length ratios, and the fast marching method (FMM). These new techniques of spurious branch removal result in the consistent removal of spurious branches without compromising the connectivity of the pulmonary circuit. Analysis of the filtered, skeletonized, and segmented 3D images is performed using a newly developed Vessel Network Extraction algorithm to fully characterize the morphology of the mouse pulmonary circuit. The removal of spurious branches from the skeletonized image results in an accurate representation of the pulmonary circuit with significantly less variability in vessel diameter and vessel length in each generation. The branching morphology of a full pulmonary circuit is characterized by the mean diameter per generation and number of vessels per generation. The methods presented in this paper lead to a significant improvement in the characterization of 3D vasculature imaging, allow for automatic separation of arteries and veins, and for the characterization of generations containing capillaries and intrapulmonary arteriovenous anastomoses (IPAVA).

The Effect of Geometric and Hemodynamic Parameters on Blood Flow Efficiency in Repaired Tetralogy of Fallot Patients.

Surgical repair of Tetralogy of Fallot (TOF) involves a series of steps to remove right ventricular outflow tract and pulmonary artery obstruction. However, the large degree of anatomic variability among preoperative TOF patients may impact the effectiveness of different repair strategies and, subsequently, different geometric modifications for different patients. This study investigates the relationships between geometric and hemodynamic parameters and mechanical energy efficiency for a patient-specific dataset of 16 postoperative TOF repairs, using morphometric and statistical shape analyses, as well as computational fluid dynamics simulations with physiologically-relevant inlet and outlet boundary conditions. Quantitatively, negative correlations were found between the right and left pulmonary artery centerline tract cumulative torsion and energy efficiency (r = - 0.65, p = 0.01, for both). A positive correlation was also found for a statistical shape mode associated with skewing of the geometric sub-regions (r = 0.61, p = 0.01). Qualitatively, medium- and low-efficiency geometries exhibit disturbed flow and much more proximal vortex formation as compared to a high-efficiency geometry. Thus, it is recommended, as much as possible, to both relieve and avoid the introduction of torsion into the patient's anatomy during surgical repair of TOF.

Computational fluid dynamics for enhanced tracheal bioreactor design and long-segment graft recellularization.

Successful re-epithelialization of de-epithelialized tracheal scaffolds remains a challenge for tracheal graft success. Currently, the lack of understanding of the bioreactor hydrodynamic environment, and its relation to cell seeding outcomes, serve as major obstacles to obtaining viable tracheal grafts. In this work, we used computational fluid dynamics to (a) re-design the fluid delivery system of a trachea bioreactor to promote a spatially uniform hydrodynamic environment, and (b) improve the perfusion cell seeding protocol to promote homogeneous cell deposition. Lagrangian particle-tracking simulations showed that low rates of rotation provide more uniform circumferential and longitudinal patterns of cell deposition, while higher rates of rotation only improve circumferential uniformity but bias cell deposition proximally. Validation experiments with human bronchial epithelial cells confirm that the model accurately predicts cell deposition in low shear stress environments. We used the acquired knowledge from our particle tracking model, as a guide for long-term tracheal repopulation studies. Cell repopulation using conditions resulting in low wall shear stress enabled enhanced re-epithelialization of long segment tracheal grafts. While our work focuses on tracheal regeneration, lessons learned in this study, can be applied to culturing of any tissue engineered tubular scaffold.

Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients.

Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.

Cardiovascular and abdominal flow alterations in adults with morphologic evidence of liver disease post Fontan palliation.

BACKGROUND: Although morphologic abnormalities in the liver are commonly encountered post Fontan palliation, the relationships between hepatic morphology, vascular flows, and clinical status remain incompletely understood. We therefore aimed to explore flow characteristics in hepatic and intestinal vessels and to examine cardiovascular associations with liver disease. METHODS: This was a retrospective study of adults post Fontan palliation undergoing clinically indicated cardiovascular magnetic resonance imaging (MRI). Patients were included if MRI flow quantification was available for cardiac, hepatic and intestinal vessels; patients were excluded if phase-contrast flow imaging was insufficient for analysis. RESULTS: Thirty patients were studied (median age at MRI 28.5 years [range 19-47]). Eighteen subjects (60%) were classified as having morphologic liver disease according to validated criteria based on available MRI imaging. Abdominal and cardiovascular flows were quantified. Patients with morphologic liver disease had a 41% reduction in superior mesenteric artery (211 ± 124 versus 358 ± 181 mL/min/m2, p = .004), a 36% reduction in hepatic vein (496 ± 247 versus 778 ± 220 mL/min/m2, p = .01), a 31% reduction in portal vein (399 ± 133 versus 580 ± 159 mL/min/m2, p = .004), and an 18% reduction in Fontan pathway flows (1358 ± 429 versus 1651 ± 270 mL/min/m2, p = .04) compared with the remaining population. Adverse cardiovascular events were not associated with morphologic liver disease. CONCLUSION: Morphologic liver disease appears to be associated with flow alterations within the heart, liver and intestine post Fontan palliation. These novel observations suggest that a potential relationship exists between morphologic disease and vascular flows thereby providing further insights into the pathophysiology of liver disease in this high-risk population.

Optimization of porous stents for endovascular repair of abdominal aortic aneurysms.

This study presents a simulation-based methodology to design porous stents to induce suitable hemodynamic environments inside abdominal aortic aneurysm (AAA) sacs. In the proposed methodology, an optimization algorithm iteratively modifies the porosity distribution of the stent and executes a computational fluid dynamics (CFD) simulation to determine the effect of these changes on the hemodynamic conditions inside the aneurysm sac. The optimization iterations proceed until relevant hemodynamic parameters are within ranges prescribed a priori by the user as desirable to control the progression of the AAA. The resulting porosity distribution uniquely describes the porous stent design that can control the hemodynamic environment (eg, shear stress at the aneurysm wall, pressure distribution, residence time), reducing AAA rupture risks and improving treatment efficacy. To demonstrate its potential, the proposed methodology is applied to idealized AAA geometry under steady-state flow conditions, though it may be easily applied to more complex AAA geometries under transient, pulsatile flow conditions. The proposed methodology has the potential to enable the design of a new generation of porous stents tailored to patient-specific geometries and flow conditions, to improve patient outcomes.

De-epithelialization of porcine tracheal allografts as an approach for tracheal tissue engineering.

Replacement of large tracheal defects remains an unmet clinical need. While recellularization of acellular tracheal grafts appeared to be a viable pathway, evidence from the clinic suggests otherwise. In hindsight, complete removal of chondrocytes and repopulation of the tracheal chondroid matrix to achieve functional tracheal cartilage may have been unrealistic. In contrast, the concept of a hybrid graft whereby the epithelium is removed and the immune-privileged cartilage is preserved is a radically different path with initial reports indicating potential clinical success. Here, we present a novel approach using a double-chamber bioreactor to de-epithelialize tracheal grafts and subsequently repopulate the grafts with exogenous cells. A 3 h treatment with sodium dodecyl sulfate perfused through the inner chamber efficiently removes the majority of the tracheal epithelium while the outer chamber, perfused with growth media, keeps most (68.6 ± 7.3%) of the chondrocyte population viable. De-epithelialized grafts support human bronchial epithelial cell (BEAS-2B) attachment, viability and growth over 7 days. While not without limitations, our approach suggests value in the ultimate use of a chimeric allograft with intact donor cartilage re-epithelialized with recipient-derived epithelium. By adopting a brief and partial decellularization approach, specifically removing the epithelium, we avoid the need for cartilage regeneration.

Impact of Insertion Technique and Iliac Artery Anatomy on Fenestrated Endovascular Aneurysm Repair.

Purpose: To develop a mechanically realistic aortoiliac model to evaluate anatomic variables associated with stent-graft rotation and to assess common deployment techniques that may contribute to rotation. Materials and Methods: Idealized aortoiliac geometries were constructed either through direct 3-dimensional (3D) printing (rigid) or through casting with polyvinyl alcohol using 3D-printed molds (flexible). Flexible model bending rigidity was controlled by altering wall thickness. Three flexible patient-specific models were also created based on the preoperative computed tomography angiograms. Zenith infrarenal and fenestrated devices were used in this study. The models were pressurized to 100 mm Hg with normal saline. Deployments were performed under fluoroscopy at 37°C. Rotation was calculated by tracking the change in position of gold markers affixed to the devices. Results: In the rigid idealized models, stent-graft rotation increased with increasing torsion; torsion levels of 1.6, 2.6, and 3.6 mm-1 had mean rotations of 5.2°±0.03°, 11.2°±4.8°, and 27.6°±13.0°, respectively (p<0.001). In the flexible models, the highest rotation (58°±3.0°) was observed in models with high torsion and high rigidity (7.5 mm-1 net torsion and 254 N·m2 flexural rigidity). No rotation was observed in the absence of torsion. Applying torque to the device during insertion significantly increased stent-graft rotation by an average of 28° across all levels of torsion (p<0.01). Multiple device insertions prior to deployment did not change the observed device rotation. The patient-specific models accurately predicted the degree of rotation seen intraoperatively to within 5°. Conclusion: Insertion technique plays an important role in the degree of stent-graft rotation during deployment. Our model suggests that in vivo correction of device orientation can increase the observed rotation and supports the concept of fully removing the device, adjusting the orientation, and subsequently reinserting. Additionally, increasing iliac artery torsion in the presence of increased vessel rigidity results in stent-graft rotation.

Comparison of Qualitative and Quantitative Assessments of Iliac Artery Tortuosity and Calcification.

INTRODUCTION: During endovascular aneurysm repair, the iliac artery typically serves as a conduit for device delivery. The degree of tortuosity and calcification in the iliac artery ultimately determines whether the device can successfully traverse the vessel. These 2 parameters can be assessed using qualitative approaches or calculated using quantitative methods based on the Society for Vascular Surgery (SVS) reporting standards. The objective of this study was to determine whether qualitative methods are sufficient to accurately assess iliac artery tortuosity and calcification by calculating interobserver variability and comparing them to the SVS Reporting Standards. METHODS: Three vascular surgeons reviewed preoperative computed tomography scans for 50 patients who underwent fenestrated endovascular aneurysm repair and qualitatively assessed left and right iliac artery tortuosity and calcification. Iliac artery geometries were segmented from these image sets. Tortuosity index and calcification length ratio were calculated and categorized based on the SVS Reporting Standards. RESULTS: Interobserver variability was calculated for the qualitative assessments using interclass correlation coefficients. For tortuosity index, among the 3 observers, good agreement was found for the left iliac artery and fair agreement was found for the right. For calcification length ratio, excellent agreement was found for both iliac arteries. When compared to the quantitative assessment, the qualitative assessments underpredicted tortuosity in 2.3% of cases, matched the quantitative values in 16.7% of cases, and overpredicted tortuosity in 81.0% of cases. The qualitative assessments underpredicted calcification in 46.3% of cases, matched the quantitative values in 49.3% of cases, and overpredicted calcification in 4.3% of cases. CONCLUSION: Qualitative assessment of iliac artery tortuosity showed fair-to-good interobserver agreement and poor agreement to SVS Reporting Standards. Qualitative assessment of iliac artery calcification showed excellent interobserver agreement and fair agreement to SVS Reporting Standards. These trends should be considered when qualitative reporting methodologies are used.

Impact of fenestrated stent graft misalignment on patient outcomes.

OBJECTIVE: During fenestrated endovascular aneurysm repair (FEVAR), accurate alignment of the fenestration and the target artery is necessary to prevent complications. This study's objective is to determine the incidence of clinical outcomes following fenestration misalignment during FEVAR. METHODS: A single-center, retrospective chart review was performed for all elective FEVARs between January 2008 and April 2015. Data were gathered from patient records and intraoperative imaging. Native vessel angles were calculated using the vessel centerlines. Intraoperative stent graft orientation was determined by changing the angle of the image intensifier as the fenestration was profiled for cannulation. Vertical fenestration misalignment was defined as 4 mm or greater and is the distance from the center of the fenestration markers to the center of the target vessel ostium at the time of cannulation. Horizontal stent graft misalignment was defined as a difference between the native vessel angle and the intraoperative fenestration angle of 15° or more. Early and late clinical outcomes were analyzed with respect to the presence of either vertical or horizontal misalignment of the renal artery fenestrations. RESULTS: The study cohort includes 65 patients who underwent FEVAR during this study period. A horizontal misalignment of 15° or more occurred in 40% of patients (n = 26) and 30° or more in 9.2% of patients (n = 6). A vertical misalignment of 4 mm or greater occurred in 32.3% of patients (n = 21). The incidence of severe postoperative complications, defined as any in-hospital end-organ ischemia and/or death, was significantly greater for patients with stent graft misalignment-31% (n = 11) vs 3% (n = 1) in the aligned group. There was a trend toward higher rates of target vessel cannulation failure in patients with stent graft misalignment 3% (n = 99 fenestrations) vs 0% (n = 76 fenestrations). The combined incidence of any intraoperative target vessel complication was significantly higher in patients with misalignment, 8.1% (4, 15) vs 1.3% (0, 8). Long-term survival was significantly lower in patients with stent graft misalignment, which was primarily driven by high intraoperative and in-hospital mortality rates (P < .05). CONCLUSIONS: Intraoperative stent graft misalignment is associated with higher rates of procedural target vessel complications and severe postoperative adverse events. Patients with stent graft misalignment should be considered at high risk for early postoperative complications. These results highlight an important need for improved FEVAR planning.