Search

Congenital heart disease affects approximately 40,000 infants annually in the United States with 25% requiring invasive treatment. Due to limited number of donor hearts and treatment options available for children, pediatric ventricular assist devices (PVADs) are used as a bridge to transplant. The 12cc pneumatic Penn State PVAD is optimized to prevent platelet adhesion and thrombus formation at patient nominal conditions; however, children demonstrate variable blood hematocrit and elevated heart rates. Therefore, with pediatric patients exhibiting greater variability, particle image velocimetry is used to evaluate the PVAD with three non-Newtonian hematocrit blood analogs (20%, 40%, and 60%) and at two beat rates (75 and 120 bpm) to understand the device’s performance. The flow fields demonstrate a strong inlet jet that transitions to a solid body rotation during diastole. During systole, the rotation dissipates and reorganizes into an outlet jet. This flow field is consistent across all hematocrits and beat rates but at a higher velocity magnitude during 120 bpm. There are also minor differences in flow field timing and surface washing due to hematocrit. Therefore, despite patient differences in hematocrit or required pumping output, thorough surface washing can be achieved in the PVAD by altering operating conditions, thus reducing platelet adhesion potential.

To address the increasing number of failing Fontan patients, Penn State University and the Penn State Hershey Medical Center are developing a centrifugal blood pump for long-term mechanical support. Computational fluid dynamics (CFD) modeling of the Penn State Fontan Circulatory Assist Device (FCAD) was performed to understand hemodynamics within the pump and its potential for hemolysis and thrombosis. CFD velocity and pressure results were first validated against experimental data and found to be within the standard deviations of the velocities and within 5% of the pressures. Further simulations performed with a human blood model found that most of the fluid domain was subjected to low shear stress (<50 Pa), with areas of highest stress around the rotor blade tips that increased with pump flow rate and rotor speed (138–178 Pa). However, the stresses compared well to previous CFD studies of commercial blood pumps and remained mostly below common thresholds of hemolysis and platelet activation. Additionally, few regions of low shear rate were observed within the FCAD, signifying minimal potential for platelet adhesion. These results further emphasize the FCAD’s potential that has been observed previously in experimental and animal studies.

Background: Both pulsatile and continuous flow ventricular assist devices are being developed for pediatric congenital heart defect patients. Pulsatile devices are often operated asynchronously with the heart in either an “automatic” or a fixed beat rate mode. However, most studies have only investigated synchronized ejection.Methods: A previously validated viscoelastic blood solver is used to investigate the parameters of pulsatility, power loss, and graft failure in a pediatric aortic anastomosis model.Results: Pulsatility was highest with synchronized flow and lowest at a 90° phase shift. Power loss decreased at 90° and 180° phase shifts but increased at a 270° phase shift. Similar regions of potential intimal hyperplasia and graft failure were seen in all cases but with phase-shifted ejection leading to higher wall shear stress on the anastomotic floor and oscillatory shear index on the anastomotic toe.Conclusion: The ranges of pulsatility and hemodynamics that can result clinically using asynchronous pulsatile devices were investigated in a pediatric anastomosis model. These results, along with the different postoperative benefits of pump modulation, can be used to design an optimal weaning protocol.

Supplemental Digital Content is available in the text.Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal’s Web site (www.asaiojournal.com) to listen.

Ventricular assist devices are a commonly used heart failure therapy for adult patients as bridge-to-transplant or bridge-to-recovery tools. The application of adult ventricular assist devices in pediatric patients has led to increased thrombotic events. Therefore, we have been developing a pediatric ventricular assist device (PVAD), the Penn State 12 cc PVAD. It is designed for patients with a body weight of 5–15 kg and has a stroke volume of 12 cc. Clot formation is the major concern. It is correlated to the coagulability of blood, the blood contacting materials and the fluid dynamics within the system. The intent is for the PVAD to be a long term therapy. Therefore, the system may be oriented in different positions according to the patient’s behavior. This study evaluates for the first time the impact of position on the flow patterns within the Penn State 12 cc PVAD, which may help to improve the PVAD design concerning chamber and ports geometries. The fluid dynamics are visualized by particle image velocimetry. The evaluation is based on inlet jet behavior and calculated wall shear rates. Vertical and horizontal model orientations are compared, both with a beat rate of 75, outlet pressures of 9060 mm Hg and a flow rate of 1.3 lmin. The results show a significant change of the inlet jet behavior and the development of a rotational flow pattern. Vertically, the inlet jet is strong along the wall. It initiates a rotational flow pattern with a wandering axis of rotation. In contrast, the horizontal model orientation results show a weaker inlet jet along the wall with a nearly constant center of rotation location, which can be correlated to a higher risk of thrombotic events. In addition, high speed videography illustrates differences in the diaphragm motion during diastole. Diaphragm opening trajectories measurements determine no significant impact of the density of the blood analog fluids. Hence, the results correlate to human blood.

Artificial organs education is often an overlooked field for many bioengineering and biomedical engineering students. The purpose of this article is to describe three different approaches to teaching artificial organs. This article can serve as a reference for those who wish to offer a similar course at their own institutions or incorporate these ideas into existing courses. Artificial organ classes typically fulfill several ABET (Accreditation Board for Engineering and Technology) criteria, including those specific to bioengineering and biomedical engineering programs.

The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study shows that implanted ventricular assist devices improve survival time and quality of life when used as a permanent therapy in patients who do not qualify for heart transplant. The success of the pulsatile 70 cc stroke volume left ventricular assist device (LVAD) developed by Penn State has led to the development of a 50 cc stroke volume pump for use in patients with smaller chest cavities to benefit a larger patient population. The initial 50 cc pump shows regions of in vivothrombus formation, which correlate to low wall shear rates within the device. In an in vitroevaluation of three new designs (V-2, V-3, and V-4) of the 50 cc LVAD, identical except for the location and orientation of their outlet ports, particle image velocimetry (PIV) is used to capture planar flow field data within the pumps. V-2 has an outlet port that is located parallel to the inlet. In V-3, the outlet port is rotated away from the inlet port, with the intention of minimizing the amount of fluid turning needed to exit the device. With V-4 the outlet port is moved to the center of the pump to prolong the desirable rotational flow. PIV data were taken at six planar locations within the pump. Although the modifications to the outlet port locations serve their intended purpose, they also introduce unwanted changes in the flow. Poorer wall washing and weaker rotational flow are observed with V-3 and V-4. Although the differences between the devices are subtle, the device that has the most desirable flow characteristics is V-2.

Because of the shortage of organs for transplant in pediatric patients with end-stage heart failure, Penn State is developing a pneumatically driven 12 cc pulsatile pediatric ventricular assist device (PVAD). A major concern is the flow field changes related to the volume decrease and its effect on device thrombogenicity. Previous studies of similar devices have shown that changes in the orientation of the inlet valve can lead to improvement in the flow field. Herein, the fluid dynamic effects of orientation changes at both the inlet and outlet valves are studied. Using two-dimensional particle image velocimetry, we examine the flow field in vitrousing an acrylic model of the PVAD in a mock circulatory loop. Regardless of valve orientation, the overall flow pattern inside the PVAD remains similar, but important differences were seen locally in the wall shear rates, which is notable because shear rates >500 s−1may prevent thrombus formation. As the inlet valve was rotated toward the fluid side of the PVAD, we observed an increase in inlet jet velocity and wall shear rates along the inlet port wall. A corresponding rotation of the outlet valve increases the wall shear rate along the outer wall near the device outlet. Wall shear rates were all higher when both valves were rotated toward the fluid side of the device, with the best rates found at orientations of 15° for both the inlet and outlet valves. Overall, orientations of 15° or 30° of both the inlet and outlet valve resulted in an increase in wall shear rates and could aid in the reduction of thrombus formation inside the PVAD.

Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because the number of available organs is insufficient, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. During myocardial recovery, the system must be weaned from the patient to prepare for explant; for pulsatile devices, this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes in flow need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time, and wall shear rates above 500 s−1, can help prevent thrombus deposition. Particle image velocimetry was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric VAD (PVAD) at a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed an earlier loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.

An unsteady computational fluid dynamic methodology was developed so that design analyses could be undertaken for devices such as the 50cc Penn State positive-displacement left ventricular assist device (LVAD). The piston motion observed in vitrowas modeled, yielding the physiologic flow waveform observed during pulsatile experiments. Valve closure was modeled numerically by locally increasing fluid viscosity during the closed phase. Computational geometry contained Bjork-Shiley Monostrut mechanical heart valves in mitral and aortic positions. Cases for computational analysis included LVAD operation under steady-flow and pulsatile-flow conditions. Computations were validated by comparing simulation results with previously obtained in vitroparticle image velocimetry (PIV) measurements. The steady portion of the analysis studied effects of mitral valve orientation, comparing the computational results with in vitrodata obtained from mock circulatory loop experiments. The velocity field showed good qualitative agreement with the in vitroPIV data. The pulsatile flow simulations modeled the unsteady flow phenomena associated with a positive-displacement LVAD operating through several beat cycles. Flow velocity gradients allowed computation of the scalar wall strain rate, an important factor for determining hemodynamics of the device. Velocity magnitude contours compared well with PIV data throughout the cycle. Computational wall shear rates over the pulsatile cycle were found to be in the same range as wall shear rates observed in vitro.

Nanoparticle Theranostics The image describes the history of different anticoagulants and diagnostics for clotting disorders, highlighting several decades without innovation. In contrast, the right side of the image depicts the development of new precision strategies, like the nanoparticle theranostic paradigm. This latter work is highlighted in article 2100520by Scott H. Medina and co‐workers. Cover design by Daryl Branford.

Deep vein thrombosis (DVT) is a life‐threatening blood clotting condition that, if undetected, can cause deadly pulmonary embolisms. Critical to its clinical management is the ability to rapidly detect, monitor, and treat thrombosis. However, current diagnostic imaging modalities lack the resolution required to precisely localize vessel occlusions and enable clot monitoring in real time. Here, we rationally design fibrinogen‐mimicking fluoropeptide nanoemulsions, or nanopeptisomes (NPeps), that allow contrast‐enhanced ultrasound imaging of thrombi and synchronous inhibition of clot growth. The theranostic duality of NPeps is imparted via their intrinsic binding to integrins overexpressed on platelets activated during coagulation. The platelet‐bound nanoemulsions can be vaporized and oscillate in an applied acoustic field to enable contrast‐enhanced Doppler ultrasound detection of thrombi. Concurrently, nanoemulsions bound to platelets competitively inhibit secondary platelet–fibrinogen binding to disrupt further clot growth. Continued development of this synchronous theranostic platform may open new opportunities for image‐guided, non‐invasive, interventions for DVT and other vascular diseases. Preventing lethal complications from deep vein thrombosis requires technologies that can rapidly detect and simultaneously treat clots forming in distal and proximal veins. Here, a simple two‐component peptide nanoemulsion that binds to activated platelets in clots to provide contrast‐enhanced ultrasound imaging of thrombosis and synchronous inhibition of clot growth is provided; all in a real‐time, non‐invasive manner.

Given the extensive and routine use of cardiovascular devices, a major limiting factor to their success is the thrombotic rate that occurs. This poses direct risk to the patient and requires counterbalancing with anticoagulation and other treatment strategies, contributing additional risks. Developing a better understanding of the mechanisms of device-induced thrombosis to aid in device design and medical management of patients is critical to advance the ubiquitous use and durability. Thus, mathematical and computational modeling of device-induced thrombosis has received significant attention recently, but challenges remain. Additional areas that need to be explored include microscopic/macroscopic approaches, reconciling physical and numerical timescales, immune/inflammatory responses, experimental validation, and incorporating pathologies and blood conditions. Addressing these areas will provide engineers and clinicians the tools to provide safe and effective cardiovascular devices.