Onur Dur

Neonatal Aortic Arch Hemodynamics and Perfusion During Cardiopulmonary Bypass

The objective of this study is to quantify the detailed three-dimensional (3D) pulsatile hemodynamics, mechanical loading, and perfusion characteristics of a patient-specific neonatal aortic arch during cardiopulmonary bypass (CPB). The 3D cardiac magnetic resonance imaging (MRI) reconstruction of a pediatric patient with a normal aortic arch is modified based on clinical literature to represent the neonatal morphology and flow conditions. The anatomical dimensions are verified from several literature sources. The CPB is created virtually in the computer by clamping the ascending aorta and inserting the computer-aided design model of the 10 Fr tapered generic cannula. Pulsatile (130 bpm) 3D blood flow velocities and pressures are computed using the commercial computational fluid dynamics (CFD) software. Second order accurate CFD settings are validated against particle image velocimetry experiments in an earlier study with a complex cardiovascular unsteady benchmark. CFD results in this manuscript are further compared with the in vivo physiological CPB pressure waveforms and demonstrated excellent agreement. Cannula inlet flow waveforms are measured from in vivo PC-MRI and 3 kg piglet neonatal animal model physiological experiments, distributed equally between the head-neck vessels and the descending aorta. Neonatal 3D aortic hemodynamics is also compared with that of the pediatric and fetal aortic stages. Detailed 3D flow fields, blood damage, wall shear stress (WSS), pressure drop, perfusion, and hemodynamic parameters describing the pulsatile energetics are calculated for both the physiological neonatal aorta and for the CPB aorta assembly. The primary flow structure is the high-speed canulla jet flow (approximately 3.0 m/s at peak flow), which eventually stagnates at the anterior aortic arch wall and low velocity flow in the cross-clamp pouch. These structures contributed to the reduced flow pulsatility (85%), increased WSS (50%), power loss (28%), and blood damage (288%), compared with normal neonatal aortic physiology. These drastic hemodynamic differences and associated intense biophysical loading of the pathological CPB configuration necessitate urgent bioengineering improvements--in hardware design, perfusion flow waveform, and configuration. This study serves to document the baseline condition, while the methodology presented can be utilized in preliminary CPB cannula design and in optimization studies reducing animal experiments. Coupled to a lumped-parameter model the 3D hemodynamic characteristics will aid the surgical decision making process of the perfusion strategies in complex congenital heart surgeries.

Computer Modeling for the Prediction of Thoracic Aortic Stent Graft Collapse

OBJECTIVE To assess the biomechanical implications of excessive stent protrusion into the aortic arch in relation to thoracic aortic stent graft (TASG) collapse by simulating the structural load and quantifying the fluid dynamics on the TASG wall protrusion extended into a model arch. METHODS One-way coupled fluid-solid interaction analyses were performed to investigate the flow-induced hemodynamic and structural loads exerted on the proximal protrusion of the TASG and aortic wall reconstructed from a patient who underwent traumatic thoracic aortic injury repair. Mechanical properties of a Gore TAG thoracic endoprosthesis (W. L. Gore and Assoc, Flagstaff, Ariz) were assessed via experimental radial compression testing and incorporated into the computational modeling. The TASG wall protrusion geometry was characterized by the protrusion extension (PE) and by the angle (θ) between the TASG and the lesser curvature of the aorta. The effect of θ was explored with the following four models with PE fixed at 1.1 cm: θ = 10 degrees, 20 degrees, 30 degrees, and 40 degrees. The effect of PE was evaluated with the following four models with θ fixed at 10 degrees: PE = 1.1 cm, 1.4 cm, 1.7 cm and 2.0 cm. RESULTS The presence of TASG wall protrusion into the aortic arch resulted in the formation of swirling, complex flow regions in the proximal luminal surface of the endograft. High PE values (PE = 2.0 cm) led to a markedly reduced left subclavian flow rate (0.27 L/min), low systolic perfusion pressure (98 mm Hg), and peak systolic TASG diameter reduction (2 mm). The transmural pressure load across the TASG was maximum for the model with the highest PE and θ, 15.2 mm Hg for the model with PE = 2.0 cm and θ = 10 degrees, and 11.6 mm Hg for PE = 1.1 cm and θ = 40 degrees. CONCLUSIONS The findings of this study suggest that increased PE imparts an apparent risk of distal end-organ malperfusion and proximal hypertension and that both increased PE and θ lead to a markedly increased transmural pressure across the TASG wall, a load that would portend TASG collapse. Patient-specific computational modeling may allow for identification of patients with high risk of TASG collapse and guide preventive intervention. CLINICAL RELEVANCE A potentially devastating complication that may occur after endovascular repair of traumatic thoracicaortic injuries is stent graft collapse. Although usually asymptomatic, stent graft collapse may be accompanied by adverse hemodynamic consequences. Numerous anatomic and device-related factors contribute to the development of collapse, but predictive factors have not yet been clearly defined. In the present study, we assessed the relevant hemodynamics and solid mechanics underlying stent graft collapse using a computational fluid-structure interaction framework of stent graft malapposition. Our findings suggest that both increased stent graft angle and extension into the aortic arch lead to a markedly increased transmural pressure across the stent graft wall, portending collapse. Patient-specific computational modeling may allow for identification of patients at high risk for collapse and aid in planning for an additional, prophylactic intervention to avert its occurrence.

Critical Transitions in Early Embryonic Aortic Arch Patterning and Hemodynamics

Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.

Right Ventricular Outflow Tract Reconstruction With Bicuspid Valved Polytetrafluoroethylene Conduit

BACKGROUND In general, all conduits available for right ventricular outflow tract (RVOT) reconstruction eventually become stenotic or insufficient. Owing to the lack of an ideal conduit and with the hope of reducing the incidence of reoperations, we have developed and utilized a bicuspid valved polytetrafluoroethylene (PTFE) conduit for the reconstruction of the RVOT. The purpose of this study was to review our early experience with this conduit. METHODS From October 2008 to September 2009, we have implanted bicuspid valved PTFE conduits in 18 patients with a median age of 1.7 years (range 6 days to 16 years). Their diagnoses include tetralogy of Fallot with pulmonary atresia in 8, truncus arteriosus in 6, congenital aortic stenosis in 2, transposition of great arteries in 1, and interrupted aortic arch with a ventricular septal defect in 1. In 16 patients, a complete biventricular repair was performed. In another 2 cases, the conduit was used for palliative RVOT reconstruction. The conduit sizes varied from 10 mm to 24 mm in diameter. Three-dimensional flow fields obtained from computational fluid dynamics studies were utilized in the conduit design process. RESULTS There was no surgical mortality or reinterventions associated with the PTFE conduit placement in our series. At the time of discharge, none of the patients had any echocardiographic findings consistent with significant conduit stenosis or insufficiency. During the follow-up period of 6.2 ± 3.9 months, all patients were alive and only 3 had more than mild pulmonary insufficiency. CONCLUSIONS Our bicuspid valved PTFE conduit has an acceptable early performance, with a low incidence of valve insufficiency and no conduit stenosis. Certainly, longer follow-up is necessary to fully assess its long-term benefits.

Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo

In the early embryo, a series of symmetric, paired vessels, the aortic arches, surround the foregut and distribute cardiac output to the growing embryo and fetus. During embryonic development, the arch vessels undergo large-scale asymmetric morphogenesis to form species-specific adult great vessel patterns. These transformations occur within a dynamic biomechanical environment, which can play an important role in the development of normal arch configurations or the aberrant arch morphologies associated with congenital cardiac defects. Arrested migration and rotation of the embryonic outflow tract during late stages of cardiac looping has been shown to produce both outflow tract and several arch abnormalities. Here, we investigate how changes in flow distribution due to a perturbation in the angular orientation of the embryonic outflow tract impact the morphogenesis and growth of the aortic arches. Using a combination of in vivo arch morphometry with fluorescent dye injection and hemodynamics-driven bioengineering optimization-based vascular growth modeling, we demonstrate that outflow tract orientation significantly changes during development and that the associated changes in hemodynamic load can dramatically influence downstream aortic arch patterning. Optimization reveals that balancing energy expenditure with diffusive capacity leads to multiple arch vessel patterns as seen in the embryo, while minimizing energy alone led to the single arch configuration seen in the mature arch of aorta. Our model further shows the critical importance of the orientation of the outflow tract in dictating morphogenesis to the adult single arch and accurately predicts arch IV as the dominant mature arch of aorta. These results support the hypothesis that abnormal positioning of the outflow tract during early cardiac morphogenesis may lead to congenital defects of the great vessels due to altered hemodynamic loading.

Pulsatile In Vitro Simulation of the Pediatric Univentricular Circulation for Evaluation of Cardiopulmonary Assist Scenarios

The characteristic depressed hemodynamic state and gradually declining circulatory function in Fontan patients necessitates alternative postoperative management strategies incorporating a system level approach. In this study, the single-ventricle Fontan circulation is modeled by constructing a practical in vitro bench-top pulsatile pediatric flow loop which demonstrates the ability to simulate a wide range of clinical scenarios. The aim of this study is to illustrate the utility of a novel single-ventricle flow loop to study mechanical cardiac assist to Fontan circulation to aid postoperative management and clinical decision-making of single ventricle patients. Two different pediatric ventricular assist devices, Medos and Pediaflow Gen-0, are anastomosed in two nontraditional configurations: systemic venous booster (SVB) and pulmonary arterial booster (PAB). Optimum ventricle assist device strategy is analyzed under normal and pathological (pulmonary hypertension) conditions. Our findings indicate that the Medos ventricular assist device in SVB configuration provided the highest increase in pulmonary (46%) and systemic (90%) venous flow under normal conditions, whereas for the hypertensive condition, highest pulmonary (28%) and systemic (55%) venous flow augmentation were observed for the Pediaflow ventricular assist device inserted as a PAB. We conclude that mechanical cardiac assist in the Fontan circulation effectively results in flow augmentation and introduces various control modalities that can facilitate patient management. Assisted circulation therapies targeting single-ventricle circuits should consider disease state specific physiology and hemodynamics on the optimal configuration decisions.

In Vitro Evaluation of Right Ventricular Outflow Tract Reconstruction With Bicuspid Valved Polytetrafluoroethylene Conduit

Conduits available for right ventricular outflow tract (RVOT) reconstruction eventually become stenotic and/or insufficient due to calcification. In order to reduce the incidence of reoperations we have developed and used a bicuspid valved polytetrafluoroethylene (PTFE) conduit for the RVOT reconstruction. The purpose of this study is to investigate the hemodynamic performance of the new design using a pediatric in vitro right heart mock loop. PTFE conduit has been used for the complete biventricular repair of 20 patients (age 1.7±6 years) with cyanotic congenital defects. To account for the large variability of conduit sizes, 14, 16, 22, and 24-mm conduit sizes were evaluated using an in vitro flow loop comprised of a pulsatile pump with cardiac output (CO) of 1.2-3.2L/min, bicuspid valved RVOT conduit, pulmonary artery, venous compartments, and the flow visualization setup. We recorded the diastolic valve leakage and pre- and post-conduit pressures in static and pulsatile settings. In vitro valve function and overall hemodynamic performance was evaluated using high-speed cameras and ultrasonic flow probes. Three-dimensional flow fields for different in vivo conduit curvatures and inflow regimes were calculated by computational fluid dynamics (CFD) analysis to further aid the conduit design process. The average pressure drop over the valved conduits was 0.8±1.7mm Hg for the CO range tested. Typical values for regurgitant fraction, peak-to-peak pressure gradient, and effective office area were 23±2.1%, 13±2.4mm Hg, and 1.56±0.2 cm(2) , respectively. High-speed videos captured the intact valve motion with asymmetrical valve opening during the systole. CFD simulations demonstrated the flow skewness toward the major curvature of the conduit based on the pulmonic curvature. In vitro evaluation of the bicuspid valved PTFE conduit coincides well with acceptable early clinical performance (mild insufficiency), with relatively low pressure drop, and intact valve motion independent from the conduit curvature, orientation or valve location, but at the expense of increased diastolic flow regurgitation. These findings benchmark the baseline performance of the bicuspid valved conduit and will be used for future designs to improve valve competency.

Hemodynamics of the hepatic venous three-vessel confluences using particle image velocimetry.

Despite rapid advancements in the patient-specific hemodynamic analysis of systemic arterial anatomies, limited attention has been given to the characterization of major venous flow components, such as the hepatic venous confluence. A detailed investigation of hepatic flow structures is essential to better understand the origin of characteristic abnormal venous flow patterns observed in patients with cardiovascular venous disease. The present study incorporates transparent rapid-prototype replicas of two pediatric hepatic venous confluence anatomies and two-component particle image velocimetry to investigate the primary flow structures influencing the inferior vena cava outflow. Novel jet flow regimes are reported at physiologically relevant mean venous conditions. The sensitivity of fluid unsteadiness and hydraulic resistance to multiple-inlet flow regimes is documented. Pressure drop measurements, jet flow characterization, and blood damage assessments are also performed. Results indicate that the orientation of the inlets significantly influences the major unsteady flow structures and power loss characteristics of this complex venous flow junction. Compared to out-of-plane arranged inlet vessel configuration, the internal flow field observed in planar inlet configurations was less sensitive to the venous inlet flow split. Under pathological flow conditions, the effective pressure drop increased as much as 77% compared to the healthy flow state. Experimental flow field results presented here can serve as a benchmark case for the surgical optimization of complex anatomical confluences including visceral hemodynamics as well as for the experimental validation of high-resolution computational fluid dynamics solvers applied to anatomical confluences with multiple inlets and outlets.

Simulation of Optimal Surgical Anastomosis of Pediatric Aortic Cannula

Ventricular assist devices (VADs) have received widespread application to treat adults with end-stage heart failure. However, application to the pediatric population has been limited due to the excessive size; and therefore miniature, pediatric VADs (PVADs) are now being developed for the pediatric population to expand the current treatment options available to young patients with congenital heart defects and acquired heart disease. These pumps are typically connected via the left ventricular apex (via an inflow cannula) to the ascending aorta (via an outflow cannula). The distal anastomosis between outflow cannula and aorta has been studied by other researchers [1, 2] revealing complex fluid dynamic phenomena due to the non-physiologic confluence of native blood flow and outflow from the VAD. The corresponding pediatric anastomosis differs in dimensions and proportions to the adult, and has not yet been studied. The objective of this initial study is to examine the influence of cannula design, location, angle of insertion, and flow rate on the macro- and micro-fluid dynamics in the pediatric aorta. This parametric study is intended to provide both developers and surgeons with insight that would lead to optimization of both the cannula and surgical procedure, with particular emphasis at avoiding recirculation and stagnation flows commonly associated with platelet activation and thrombus generation [2, 3].Copyright

Effect of Caval Waveform on Energy Dissipation of Failing Fontan Patients

Last stage of the palliative surgical reconstruction (i.e. Fontan procedure) for the infants with functional single-ventricle is total cavopulmonary connection (TCPC), where the superior vena cavae (SVC) and inferior vena cavae (IVC) are routed directly into the pulmonary arteries. Limited pumping energy available due to the absence of right-ventricle and altered venous characteristics require optimized hemodynamics inside the TCPC pathway, which can be achieved by minimizing the power losses.Copyright