An arteriovenous mock circulatory loop and accompanying bond graph model for in vitro study of peripheral intravascular bioartificial organs.

BACKGROUND: Silicon nanopore membrane-based implantable bioartificial organs are dependent on arteriovenous implantation of a mechanically robust and biocompatible hemofilter. The hemofilter acts as a low-resistance, high-flow network, with blood flow physiology similar to arteriovenous shunts commonly created for hemodialysis access. A mock circulatory loop (MCL) that mimics shunt physiology is an essential tool for refinement and durability testing of arteriovenous implantable bioartificial organs and silicon blood-interfacing membranes. We sought to develop a compact and cost-effective MCL to replicate flow conditions through an arteriovenous shunt and used data from the MCL and swine to inform a bond graph mathematical model of the physical setup. METHODS: Flow physiology through bioartificial organ prototypes was obtained in the MCL and during extracorporeal attachment to swine for biologic comparison. The MCL was tested for stability overtime by measuring pressurewave variability over a 48-h period. Data obtained in vitro and extracorporeally informed creation of a bond graph model of the MCL. RESULTS: The arteriovenous MCL was a cost-effective, portable system that reproduced flow rates and pressures consistent with a pulsatile arteriovenous shunt as measured in swine. MCL performance was stable over prolonged use, providing a cost-effective simulator for enhanced testing of peripherally implanted bioartificial organ prototypes. The corresponding bond graph model recapitulates MCL and animal physiology, offering a tool for further refinement of the MCL system.

Enhancing cerebral vasculature analysis with pathlength-corrected 2D angiographic parametric imaging: A feasibility study.

BACKGROUND: 2D angiographic parametric imaging (API) quantitatively extracts imaging biomarkers related to contrast flow and is conventionally applied to 2D digitally subtracted angiograms (DSA's). In the interventional suite, API is typically performed using 1-2 projection views and is limited by vessel overlap, foreshortening, and depth-integration of contrast motion. PURPOSE: This work explores the use of a pathlength-correction metric to overcome the limitations of 2D-API: the primary objective was to study the effect of converting 3D contrast flow to projected contrast flow using a simulated angiographic framework created with computational fluid dynamics (CFD) simulations, thereby removing acquisition variability. METHODS: The pathlength-correction framework was applied to in-silico angiograms, generating a reference (i.e., ground-truth) volumetric contrast distribution in four patient-specific intracranial aneurysm geometries. Biplane projections of contrast flow were created from the reference volumetric contrast distributions, assuming a cone-beam geometry. A Parker-weighted reconstruction was performed to obtain a binary representation of the vessel structure in 3D. Standard ray tracing techniques were then used to track the intersection of a ray from the focal spot with each voxel of the reconstructed vessel wall to a pixel in the detector plane. The lengths of each ray through the 3D vessel lumen were then projected along each ray-path to create a pathlength-correction map, where the pixel intensity in the detector plane corresponds to the vessel width along each source-detector ray. By dividing the projection sequences with this correction map, 2D pathlength-corrected in-silico angiograms were obtained. We then performed voxel-wise (3D) API on the ground-truth contrast distribution and compared it to pixel-wise (2D) API, both with and without pathlength correction for each biplane view. The percentage difference (PD) between the resultant API biomarkers in each dataset were calculated within the aneurysm region of interest (ROI). RESULTS: Intensity-based API parameters, such as the area under the curve (AUC) and peak height (PH), exhibited notable changes in magnitude and spatial distribution following pathlength correction: these now accurately represent conservation of mass of injected contrast media within each arterial geometry and accurately reflect regions of stagnation and recirculation in each aneurysm ROI. Improved agreement was observed between these biomarkers in the pathlength-corrected biplane maps: the maximum PD within the aneurysm ROI is 3.3% with pathlength correction and 47.7% without pathlength correction. As expected, improved agreement with ROI-averaged ground-truth 3D counterparts was observed for all aneurysm geometries, particularly large aneurysms: the maximum PD for both AUC and PH was 5.8%. Temporal parameters (mean transit time, MTT, time-to-peak, TTP, time-to-arrival, TTA) remained unaffected after pathlength correction. CONCLUSIONS: This study indicates that the values of intensity-based API parameters obtained with conventional 2D-API, without pathlength correction, are highly dependent on the projection orientation, and uncorrected API should be avoided for hemodynamic analysis. The proposed metric can standardize 2D API-derived biomarkers independent of projection orientation, potentially improving the diagnostic value of all acquired 2D-DSA's. Integration of a pathlength correction map into the imaging process can allow for improved interpretation of biomarkers in 2D space, which may lead to improved diagnostic accuracy during procedures involving the cerebral vasculature.

Encouraging Regular Aortic Valve Opening for EVAHEART 2 LVAD Support Using Virtual Patient Hemodynamic Speed Modulation Analysis.

This study focuses on investigating the EVAHEART 2 left ventricular assist device (LVAD) toward designing optimal pump speed modulation (PSM) algorithms for encouraging aortic valve (AV) flow. A custom-designed virtual patient hemodynamic model incorporating the EVAHEART 2 pressure-flow curves, cardiac chambers, and the systemic and pulmonary circulations was developed and used in this study. Several PSM waveforms were tested to evaluate their influence on the mean arterial pressure (MAP), cardiac output (CO), and AV flow for representative heart failure patients. Baseline speeds were varied from 1,600 to 2,000 rpm. For each baseline speed, the following parameters were analyzed: 1) PSM ratio (reduced speed/baseline speed), 2) PSM duration (3-7 seconds), 3) native ventricle contractility, and 4) patient MAP of 70 and 80 mm Hg. More than 2,000 rpm virtual patient scenarios were explored. A lower baseline speed (1,600 and 1,700 rpm) produced more opportunities for AV opening and more AV flow. Higher baseline speeds (1,800 and 2,000 rpm) had lower or nonexistent AV flow. When analyzing PSM ratios, a larger reduction in speed (25%) over a longer PSM (5+ seconds) duration produced the most AV flow. Lower patient MAP and increased native ventricle contractility also contributed to improving AV opening frequency and flow. This study of the EVAHEART 2 LVAD is the first to focus on leveraging PSM to enhance pulsatility and encourage AV flow. Increased AV opening frequency can benefit aortic root hemodynamics, thereby improving patient outcomes.

Modeling Gasotransmitter Availability to Brain Capillary Endothelial Cells with Ultrasound-sensitive Microbubbles.

BACKGROUND: Vascular cognitive impairment and dementia results from blood components passing through disrupted blood brain barriers (BBBs). Current treatments can reduce further progress of neuronal damage but do not treat the primary cause. Instead, these treatments typically aim to temporarily disrupt the BBB. Alternatively, this study computationally assessed the feasibility of delivering carbon monoxide (CO) from ultrasound-sensitive microbubbles (MBs) as a strategy to promote BBB repair and integrity. CO can interact with heme-containing compounds within cells and promote cell growth. However, careful dose control is critical for safety and efficacy because CO also binds at high affinity to hemoglobin (Hb). METHODS: Ultrasound activation was simulated at the internal carotid artery, and CO released from the resulting MB rupture was tracked along the shortest path to the BBB for several activation times and doses. The CO dose available to brain capillary endothelial cells (BCECs) was predicted by considering hemodynamics, mass transport, and binding kinetics. RESULTS: The half-life of CO binding to Hb indicated that CO is available to interact with BCECs for several cardiac cycles. Further, MB and COHb concentrations would not be near toxic levels and free Hb would be available. The axisymmetric model indicated that biologically-relevant CO concentrations will be available to BCECs, and these levels can be sustained with controlled ultrasound activation. A patient-specific geometry shows that while vessel tortuosity provides a heterogeneous response, a relevant CO concentration could still be achieved. CONCLUSIONS: This computational study demonstrates feasibility of the CO / MB strategy, and that controlled delivery is important for viability of this strategy.

Application of 1,000 fps High-Speed Angiography to In-Vitro Hemodynamic Evaluation of Left Ventricular Assist Device Outflow Graft Configurations.

Left ventricular assist device (LVAD)-induced hemodynamics are characterized by fast-moving flow with large variations in velocity, making quantitative assessments difficult with existing imaging methods. This study demonstrates the ability of 1,000 fps high-speed angiography (HSA) to quantify the effect of the surgical implantation angle of a LVAD outflow graft on the hemodynamics within the ascending aorta in vitro . High-speed angiography was performed on patient-derived, three-dimensional-printed optically opaque aortic models using a nonsoluble contrast media, ethiodol, as a flow tracer. Outflow graft configuration angles of 45° and 90° with respect to the central aortic axis were considered. Projected velocity distributions were calculated from the high-speed experimental sequences using two methods: a physics-based optical flow algorithm and tracking of radio-opaque particles. Particle trajectories were also used to evaluate accumulated shear stress. Results were then compared with computational fluid dynamics (CFD) simulations to confirm the results of the high-speed imaging method. Flow patterns derived from HSA coincided with the impingement regions and recirculation zones formed in the aortic root as seen in the CFD for both graft configurations. Compared with the 45° graft, the 90° configuration resulted in 81% higher two-dimensional-projected velocities (over 100 cm/s) along the contralateral wall of the aorta. Both graft configurations suggest elevated accumulated shear stresses along individual trajectories. Compared with CFD simulations, HSA successfully characterized the fast-moving flow and hemodynamics in each LVAD graft configuration in vitro , demonstrating the potential utility of this technology as a quantitative imaging modality.

A Computational Hemodynamics Approach to Left Ventricular Assist Device (LVAD) Optimization Validated in a Large Patient Cohort.

With increasing use of left ventricular assist devices (LVAD) it is critical to devise strategies to optimize LVAD speed while controlling mean arterial pressure (MAP) and flow according to patient physiology. The complex interdependency between LVAD speed, MAP, and flow frequently makes optimization difficult under clinical conditions. We propose a method to guide this procedure in silico, narrowing the conditions to test clinically. A computational model of the circulatory network that simulates HF and LVAD support, incorporating LVAD pressure-flow curves was applied retrospectively to anonymized patient hemodynamics data from the University of Washington Medical Center. MAP management on 61 patient-specific computational models with a target of 70 mm Hg, resulting flow for a given LVAD speed was analyzed, and compared to a target output of 5 L/min. Before performing virtual MAP management, 51% had a MAP>70 mm Hg and CO>5 L/min, and 33% had a MAP>70 mm Hg and CO<5 L/min. After changing systemic resistance to meet the MAP target (without adjusting LVAD speed), 84% of cases resulted in CO higher than 5 L/min, with a median CO of 6.79 L/min, using the computational predictive model. Blood pressure management alone is insufficient in meeting both MAP and CO targets, due to the risk of hypervolemia, and requires appropriate LVAD speed optimization to achieve both targets, while preserving right heart health. Such computational tools can narrow down conditions to be tested for each patient, providing significant insight into the pump-patient interplay. LVAD hemodynamic optimization has the potential to reduce complications and improve outcomes.

Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

In Vitro Investigation of the Effect of Left Ventricular Assist Device Speed and Pulsatility Mode on Intraventricular Hemodynamics.

Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left ventricle are altered by the implantation of an LVAD, with the increase of thrombogenic flow patterns, such as stagnation regions. Time-resolved stereo particle image velocimetry (Stereo-PIV) measurements of the flow inside a patient-specific model of the left ventricle (LV) implanted with an LVAD were performed. The effects of LVAD speed, peripheral resistance and afterload were investigated. The impact of activating the LVAD pulsatility mode (periodic speed modulation) was also evaluated. Analysis of the velocity measurements in two orthogonal planes revealed stagnation zones which may be favorable to thrombus formation. Increasing LVAD speed, despite increasing the flow rate through the inflow cannula, does not automatically result in smaller stagnation regions. These results demonstrated the strong interdependence of peripheral resistance, afterload and flow through the LVAD. As a consequence, the pulsatility mode showed very limited effect on overall flow rate. However, it did reduce the size of high stagnation areas. This study showed how LVAD speed, peripheral resistance and afterload impact the complex intraventricular flow patterns in a ventricle implanted with an LVAD and quantify their thrombogenic risk.

Platelet Dynamics and Hemodynamics of Cerebral Aneurysms Treated with Flow-Diverting Stents.

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy.

Left Ventricular Assist Device Inflow Cannula Insertion Depth Influences Thrombosis Risk.

Left ventricular assist device (LVAD) use has continued to grow. Despite recent advances in technology, LVAD patients continue to suffer from devastating complications, including stroke and device thrombosis. Among several variables affecting thrombogenicity, we hypothesize that insertion depth of the inflow cannula into the left ventricle (LV) influences hemodynamics and thrombosis risk. Blood flow patterns were studied in a patient-derived computational model of the LV, mitral valve (MV), and LVAD inflow cannula using unsteady computational fluid dynamics (CFD). Hundreds of thousands of platelets were tracked individually, for two inflow cannula insertion depth configurations (12 mm-reduced and 27 mm-conventional) using platelet-level (Lagrangian) metrics to quantify thrombogenicity. Particularly in patients with small LV dimensions, the deeper inflow cannula insertion resulted in much higher platelet shear stress histories (SH), consistent with markedly abnormal intraventricular hemodynamics. A larger proportion of platelets in this deeper insertion configuration was found to linger in the domain for long residence times (RT) and also accumulated much higher SH. The reduced inflow depth configuration promoted LV washout and reduced platelet SH. The increase of both SH and RT in the LV demonstrates the impact of inflow cannula depth on platelet activation and increased stroke risk in these patients. Inflow cannula depth of insertion should be considered as an opportunity to optimize surgical planning of LVAD therapy.

Accuracy of Doppler blood pressure measurement in continuous-flow left ventricular assist device patients.

AIMS: Accurate blood pressure (BP) measurement in continuous-flow ventricular assist device (CF-VAD) patients is imperative to reduce stroke risk. This study assesses the accuracy of the Doppler opening pressure method compared with the gold standard arterial line method in CF-VAD patients. METHODS AND RESULTS: In a longitudinal cohort of HeartMate II and HVAD patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Overall correlation, agreement between Doppler opening pressure and arterial line mean vs. systolic pressure, and the effect of arterial pulsatility on the accuracy of Doppler opening pressure were analysed. A total of 1933 pairs of Doppler opening pressure and arterial line pressure readings within 1 min of each other were identified in 154 patients (20% women, mean age 55 ± 15, 50% HeartMate II and 50% HVAD). Doppler opening pressure had good correlation with invasive mean arterial pressure (r = 0.742, P < 0.0001) and more closely approximated mean than systolic BP (mean error 2.4 vs. -8.4 mmHg). Arterial pulsatility did not have a clinically significant effect on the accuracy of the Doppler opening pressure method. CONCLUSIONS: Doppler opening pressure should be the standard non-invasive method of BP measurement in CF-VAD patients.

Small Left Ventricular Size Is an Independent Risk Factor for Ventricular Assist Device Thrombosis.

The prevalence of ventricular assist device (VAD) therapy has continued to increase due to a stagnant donor supply and growing advanced heart failure (HF) population. We hypothesize that left ventricular (LV) size strongly influences biocompatibility and risk of thrombosis. Unsteady computational fluid dynamics (CFD) was used in conjunction with patient-derived computational modeling and virtual surgery with a standard, apically implanted inflow cannula. A dual-focus approach of evaluating thrombogenicity was employed: platelet-based metrics to characterize the platelet environment and flow-based metrics to investigate hemodynamics. Left ventricular end-diastolic dimensions (LVEDds) ranging from 4.5 to 6.5 cm were studied and ranked according to relative thrombogenic potential. Over 150,000 platelets were individually tracked in each LV model over 15 cardiac cycles. As LV size decreased, platelets experienced markedly increased shear stress histories (SHs), whereas platelet residence time (RT) in the LV increased with size. The complex interplay between increased SH and longer RT has profound implications on thrombogenicity, with a significantly higher proportion of platelets in small LVs having long RT times and being subjected to high SH, contributing to thrombus formation. Our data suggest that small LV size, rather than decreased VAD speed, is the primary pathologic mechanism responsible for the increased incidence of thrombosis observed in VAD patients with small LVs.

Reconstructing patient-specific cerebral aneurysm vasculature for in vitro investigations and treatment efficacy assessments.

Perianeurysmal hemodynamics play a vital role in the initiation, growth and rupture of intracranial aneurysms. In vitro investigations of aneurysmal hemodynamics are helpful to visualize and measure blood flow, and aiding surgical planning approaches. Improving in vitro model creation can improve the feasibility and accuracy of hemodynamic investigations and surgical planning, improving clinical value. In this study, in vitro models were created from three-dimensional rotational angiography (3DRA) of six patients harboring intracranial aneurysms using a multi-step process involving 3D printing, index of refraction matching and silicone casting that renders the models transparent for flow visualization. Each model was treated with the same commercially-available, patient-specific, endovascular devices (coils and/or stents). All models were scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the vessel lumen, aneurysmal sac and endovascular devices. Dimensional accuracy was compared by quantifying the differences between the microtomographic reconstructions of the fabricated phantoms and the original 3DRA obtained during patient treatment. True-scale in vitro flow phantoms were successfully created for all six patients. Optical transparency was verified by using an index of refraction matched working fluid that replicated the mechanical behavior of blood. Synchrotron imaging of vessel lumen, aneurysmal sac and endovascular devices was successfully obtained, and dimensional errors were found to be O(100 µm). The creation of dimensionally-accurate, optically-transparent flow phantoms of patient-specific intracranial aneurysms is feasible using 3D printing technology. Such models may enable in vitro investigations of aneurysmal hemodynamics to aid in treatment planning and outcome prediction to devise optimal patient-specific neurointerventional strategies.

Blood damage in Left Ventricular Assist Devices: Pump thrombosis or system thrombosis?

INTRODUCTION:: Despite significant technical advancements in the design and manufacture of Left Ventricular Assist Devices, post-implant thrombotic and thromboembolic complications continue to affect long-term outcomes. Previous efforts, aimed at optimizing pump design as a means of reducing supraphysiologic shear stresses generated within the pump and associated prothrombotic shear-mediated platelet injury, have only partially altered the device hemocompatibility. METHODS:: We examined hemodynamic mechanisms that synergize with hypershear within the pump to contribute to the thrombogenic potential of the overall Left Ventricular Assist Device system. RESULTS:: Numerical simulations of blood flow in differing regions of the Left Ventricular Assist Device system, that is the diseased native left ventricle, the pump inflow cannula, the impeller, the outflow graft and the anastomosed downstream aorta, reveal that prothrombotic hemodynamic conditions might occur at these specific sites. Furthermore, we show that beyond hypershear, additional hemodynamic abnormalities exist within the pump, which may elicit platelet activation, such as recirculation zones and stagnant platelet trajectories. We also provide evidences that particular Left Ventricular Assist Device implantation configurations and specific post-implant patient management strategies, such as those allowing aortic valve opening, are more hemodynamically favorable and reduce the thrombotic risk. CONCLUSION:: We extend the perspective of pump thrombosis secondary to the supraphysiologic shear stress environment of the pump to one of Left Ventricular Assist Device system thrombosis, raising the importance of comprehensive characterization of the different prothrombotic risk factors of the total system as the target to achieve enhanced hemocompatibility and improved clinical outcomes.

Left Ventricular Assist Device Inflow Cannula Angle and Thrombosis Risk.

BACKGROUND: As heart failure prevalence continues to increase in the setting of a static donor supply, left ventricular assist device (LVAD) therapy for end-stage heart failure continues to grow. Anecdotal evidence suggests that malalignment of the LVAD inflow cannula may increase thrombosis risk, but this effect has not been explored mechanistically or quantified statistically. Our objective is to elucidate the impact of surgical angulation of the inflow cannula on thrombogenicity. METHODS AND RESULTS: Unsteady computational fluid dynamics is used in conjunction with computational modeling and virtual surgery to model flow through the left ventricle for 5 different inflow cannula angulations. We use a holistic approach to evaluate thrombogenicity: platelet-based (Lagrangian) metrics to evaluate the platelet mechanical environment, combined with flow-based (Eulerian) metrics to investigate intraventricular hemodynamics. The thrombogenic potential of each LVAD inflow cannula angulation is quantitatively evaluated based on platelet shear stress history and residence time. Intraventricular hemodynamics are strongly influenced by LVAD inflow cannula angulation. Platelet behavior indicates elevated thrombogenic potential for certain inflow cannula angles, potentially leading to platelet activation. Our analysis demonstrates that the optimal range of inflow angulation is within 0±7° of the left ventricular apical axis. CONCLUSIONS: Angulation of the inflow cannula >7° from the apical axis (axis connecting mitral valve and ventricular apex) leads to markedly unfavorable hemodynamics as determined by computational fluid dynamics. Computational hemodynamic simulations incorporating Lagrangian and Eulerian metrics are a powerful tool for studying optimization of LVAD implantation strategies, with the long-term potential of improving outcomes.

Hyperglycemia Alters the Structure and Hemodynamics of the Developing Embryonic Heart.

Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3-5 fold. During heart organogenesis, little is known about the effects of hyperglycemia on hemodynamics, which are critical to normal heart development. Heart development prior to septation in the chick embryo was studied under hyperglycemic conditions. Sustained hyperglycemic conditions were induced, raising the average plasma glucose concentration from 70 mg/dL to 180 mg/dL, akin to the fasting plasma glucose of a patient with diabetes. The OFTs were assessed for structural and hemodynamic alterations using optical coherence tomography (OCT), confocal microscopy, and microcomputed tomography. In hyperglycemic embryos, the endocardial cushions of the proximal OFT were asymmetric, and the OFTs curvature and torsion were significantly altered. The blood flow velocity through the OFT of hyperglycemic embryos was significantly decreased, including flow reversal in 30% of the cardiac cycle. Thus, hyperglycemia at the onset of gestation results in asymmetric proximal endocardial cushions, abnormal OFT curvature, and altered hemodynamics in the developing heart. If present in humans, these results may identify early developmental alterations that contribute to the increased risk for cardiac malformations in babies from diabetic mothers.

Intermittent Aortic Valve Opening and Risk of Thrombosis in Ventricular Assist Device Patients.

The current study evaluates quantitatively the impact that intermittent aortic valve (AV) opening has on the thrombogenicity in the aortic arch region for patients under left ventricular assist device (LVAD) therapy. The influence of flow through the AV, opening once every five cardiac cycles, on the flow patterns in the ascending aortic is measured in a patient-derived computed tomography image-based model, after LVAD implantation. The mechanical environment of flowing platelets is investigated, by statistical treatment of outliers in Lagrangian particle tracking, and thrombogenesis metrics (platelet residence times and activation state characterized by shear stress accumulation) are compared for the cases of closed AV versus intermittent AV opening. All hemodynamics metrics are improved by AV opening, even at a reduced frequency and flow rate. Residence times of platelets or microthrombi are reduced significantly by transvalvular flow, as are the shear stress history experienced and the shear stress magnitude and gradients on the aortic root endothelium. The findings of this device-neutral study support the multiple advantages of management that enables AV opening, providing a rationale for establishing this as a standard in long-term treatment and care for advanced heart failure patients.

LVAD Outflow Graft Angle and Thrombosis Risk.

This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization. Accurate platelet-level investigation, enabled by statistical treatment of outliers in Lagrangian particle tracking, demonstrates a strong influence of outflow graft anastomoses angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced TP for acutely-angled anastomosed outflow grafts. The methodology presented in this study provides a device-neutral platform for conducting comprehensive thrombogenicity evaluation of LVAD surgical configurations, empowering optimal patient-focused surgical strategies for long-term treatment and care for advanced heart failure patients.

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

BACKGROUND: Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. METHODS: Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. RESULTS: We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. CONCLUSIONS: We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at smaller diameters. AOO appears to increase PWS, whereas COPD and PAD may be surrogate markers of decreased aortic wall strength. We therefore recommend consideration of early, elective AAA repair in patients with AOO, PAD, or COPD to minimize risk of early rupture.

Effect of Outflow Tract Banding on Embryonic Cardiac Hemodynamics.

We analyzed heart wall motion and blood flow dynamics in chicken embryos using in vivo optical coherence tomography (OCT) imaging and computational fluid dynamics (CFD) embryo-specific modeling. We focused on the heart outflow tract (OFT) region of day 3 embryos, and compared normal (control) conditions to conditions after performing an OFT banding intervention, which alters hemodynamics in the embryonic heart and vasculature. We found that hemodynamics and cardiac wall motion in the OFT are affected by banding in ways that might not be intuitive a priori. In addition to the expected increase in ventricular blood pressure, and increase blood flow velocity and, thus, wall shear stress (WSS) at the band site, the characteristic peristaltic-like motion of the OFT was altered, further affecting flow and WSS. Myocardial contractility, however, was affected only close to the band site due to the physical restriction on wall motion imposed by the band. WSS were heterogeneously distributed in both normal and banded OFTs. Our results show how banding affects cardiac mechanics and can lead, in the future, to a better understanding of mechanisms by which altered blood flow conditions affect cardiac development leading to congenital heart disease.