Effect of Hematocrit and Elevated Beat Rate on the 12cc Penn State Pediatric Ventricular Assist Device.

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.

Experimental Hemodynamics Within the Penn State Fontan Circulatory Assist Device.

For children born with a single functional ventricle, the Fontan operation bypasses the right ventricle by forming a four-way total cavopulmonary connection and adapts the existing ventricle for the systemic circulation. However, upon reaching adulthood, many Fontan patients exhibit low cardiac output and elevated venous pressure, eventually requiring a heart transplantation. Despite efforts in developing a new device or using an existing device for failing Fontan support, there is still no Food and Drug Administration-approved device for subpulmonary support. Penn State University is developing a hydrodynamically levitated Fontan circulatory assist device (FCAD) for bridge-to-transplant or destination therapy. The hemodynamics within the FCAD, at both steady and patient averaged pulsatile conditions for three physiological pump operating conditions, were quantified using particle image velocimetry (PIV) to determine the velocity magnitudes and Reynolds normal and shear stresses within the device. Data were acquired at three planes (0 mm and ±25% of the radius) for the inferior and superior vena cavae inlets and the pulmonary artery outlet. The inlets had a blunt velocity profile that became skewed toward the collecting volute as fluid approached the rotor. At the outlet, regardless of the flow condition, a high-velocity jet exited the volute and moved downstream in a helical pattern. Turbulent stresses observed at the volute exit were influenced by the rotor's rotation. Regardless of inlet conditions, the pump demonstrated advantageous behavior for clinical use with a predictable flow field and a low risk of platelet adhesion and hemolysis based on calculated wall shear rates and turbulent stresses, respectively.

Transcatheter Heart Valve Downstream Fluid Dynamics in an Accelerated Evaluation Environment.

Transcatheter aortic valve replacements (TAVRs) provide minimally invasive delivery of bioprosthetic heart valves (BHVs) for the treatment of aortic valve disease. While surgical BHVs show efficacy for 8-10 years, long-term TAVR durability remains unknown. Pre-clinical testing evaluates BHV durability in an ISO:5840 compliant accelerated wear tester (AWT), yet, the design and development of AWTs and their accuracy in predicting in vivo performance, is unclear. As a result of limited knowledge on AWT environment and BHV loading, durability assessment of candidate valves remains fundamentally empirical. For the first time, high-speed particle image velocimetry quantified an ISO:5840 compliant downstream AWT velocity field, Reynolds stresses, and turbulence intensity. TAVR enface imaging quantified the orifice area and estimated the flow rate. When valve area and flow rate were at their maximum during peak systole (1.49 cm2 and 16.05 L/min, respectively), central jet velocity, Reynolds normal and shear stress, and turbulence intensity grew to 0.50 m/s, 265.1 Pa, 124.6 Pa, and 37.3%, respectively. During diastole, unique AWT recirculation produced retrograde flow and the directional changes created eddies. These novel AWT findings demonstrated a substantially reduced valve fully loaded period and pressure not matching in vivo or in vitro studies, despite the comparable fluid environment and TAVR motion.

An enlarging pacemaker pocket: A case report of a plasmablastic lymphoma arising as a primary tumor around a cardiac pacemaker and systematic literature review of various malignancies arising at the pacemaker pocket.

To date, there have been limited reports of oncogenesis occurring within pacemaker pockets. We report the case of a 100-year-old male who presented to the emergency department complaining of expansion of his pacemaker pocket over the period of 8 days. Dissection of the pacemaker pocket and pathological analysis of tissue samples revealed plasmablastic lymphoma, a subset of diffuse large B-cell lymphoma, commonly seen in immunocompromised elderly patients. This is the first known reported case of plasmablastic lymphoma occurring within a pacemaker pocket. .

Acquired Von Willebrand Syndrome and Blood Pump Design.

The existence of acquired von Willebrand syndrome (AVWS) in patients with continuous flow left ventricular assist devices (LVADs) is well documented and has been verified by numerous investigators. AVWS has not been observed to occur in pulsatile devices such as the SynCardia total artificial heart (TAH), the HeartMate XVE, and the Thoratec pulsatile ventricular assist device (PVAD) used as a single pump. AVWS can also occur in patients with aortic stenosis, ventricular septal defect, mitral stenosis, and patent ductus arteriosus. It has been experimentally verified that supraphysiologic shear stress that occurs under these conditions can cleave the von Willebrand molecule, but the critical magnitude of stress and duration is unclear. Limited experimental results demonstrate that shear stresses as low as 5 Pa (50 dyne/cm2 ) can cause cleavage. Stresses in current centrifugal pumps can be as high as two orders of magnitude greater than this value. Pulsatile LVADs have stresses almost two orders of magnitude less than continuous flow LVADs. In order to improve continuous flow LVADs, the challenge for designers is to first determine the magnitude and duration of stress that is causing AVWS and then, if possible, design a pump below these stresses.

Characterizing the HeartMate II Left Ventricular Assist Device Outflow Using Particle Image Velocimetry.

Ventricular assist devices (VADs) are implanted in patients with a diseased ventricle to maintain peripheral perfusion as a bridge-to-transplant or as destination therapy. However, some patients with continuous flow VADs (e.g., HeartMate II (HMII)) have experienced gastrointestinal (GI) bleeding, in part caused by the proteolytic cleavage or mechanical destruction of von Willebrand factor (vWF), a clotting glycoprotein. in vitro studies were performed to measure the flow located within the HMII outlet cannula under both steady and physiological conditions using particle image velocimetry (PIV). Under steady flow, a mock flow loop was used with the HMII producing a flow rate of 3.2 L/min. The physiological experiment included a pulsatile pump operated at 105 BPM with a ventricle filling volume of 50 mL and in conjunction with the HMII producing a total flow rate of 5.0 L/min. Velocity fields, Reynolds normal stresses (RNSs), and Reynolds shear stresses (RSSs) were analyzed to quantify the outlet flow's potential contribution to vWF degradation. Under both flow conditions, the HMII generated principal Reynolds stresses that are, at times, orders of magnitude higher than those needed to unfurl vWF, potentially impacting its physiological function. Under steady flow, principal RNSs were calculated to be approximately 500 Pa in the outlet cannula. Elevated Reynolds stresses were observed throughout every phase of the cardiac cycle under physiological flow with principal RNSs approaching 1500 Pa during peak systole. Prolonged exposure to these conditions may lead to acquired von Willebrand syndrome (AvWS), which is accompanied by uncontrollable bleeding episodes.

Asynchronous Pumping of a Pulsatile Ventricular Assist Device in a Pediatric Anastomosis Model.

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.

FDA Benchmark Medical Device Flow Models for CFD Validation.

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.

Development of a platelet adhesion transport equation for a computational thrombosis model.

Thrombosis is a significant issue for cardiovascular device development and use. While thrombosis models are available, very few are device-related and none have been thoroughly validated experimentally. Here, we introduce a surface adherent platelet transport equation into a continuum model to account for the biomaterial interface/blood interaction. Using a rotating disc system and polyurethane-urea material, we characterize steady and pulsatile flow fields using laser Doppler velocimetry. In vitro measurements of platelet adhesion are used in combination with the LDV data to provide further experimental validation. The rotating disc system is computationally studied using the device-induced thrombosis model with the surface platelet adherent transport equation. The results indicate that the flow field is in excellent agreement to the experimental LDV data and that the platelet adhesion simulations are in good agreement with the in vitro platelet data. These results provide good evidence that this transport equation can be used to express the relationship between blood and a biomaterial if the correct platelet adhesion characteristics are known for the biomaterial. Further validation is necessary with other materials.

Analysis of Transitional and Turbulent Flow Through the FDA Benchmark Nozzle Model Using Laser Doppler Velocimetry.

Transitional and turbulent flow through a simplified medical device model is analyzed as part of the FDA's Critical Path Initiative, designed to improve the process of bringing medical products to market. Computational predictions are often used in the development of devices and reliable in vitro data is needed to validate computational results, particularly estimations of the Reynolds stresses that could play a role in damaging blood elements. The high spatial resolution of laser Doppler velocimetry (LDV) is used to collect two component velocity data within the FDA benchmark nozzle model. Two flow conditions are used to produce flow encompassing laminar, transitional, and turbulent regimes, and viscous stresses, principal Reynolds stresses, and turbulence intensities are calculated from the measured LDV velocities. Axial velocities and viscous stresses are compared to data from a prior inter-laboratory study conducted with particle image velocimetry. Large velocity gradients are observed near the wall in the nozzle throat and in the jet shear layer located in the expansion downstream of the throat, with axial velocity changing as much as 4.5 m/s over 200 µm. Additionally, maximum Reynolds shear stresses of 1000-2000 Pa are calculated in the high shear regions, which are an order of magnitude higher than the peak viscous shear stresses (<100 Pa). It is important to consider the effects of both viscous and turbulent stresses when simulating flow through medical devices. Reynolds stresses above commonly accepted hemolysis thresholds are measured in the nozzle model, indicating that hemolysis may occur under certain flow conditions. As such, the presented turbulence quantities from LDV, which are also available for download at https://fdacfd.nci.nih.gov/ , provide an ideal validation test for computational simulations that seek to characterize the flow field and to predict hemolysis within the FDA nozzle geometry.

Development of a computational model for macroscopic predictions of device-induced thrombosis.

While cardiovascular device-induced thrombosis is associated with negative patient outcomes, the convoluted nature of the processes resulting in a thrombus makes the full thrombotic network too computationally expensive to simulate in the complex geometries and flow fields associated with devices. A macroscopic, continuum computational model is developed based on a simplified network, which includes terms for platelet activation (chemical and mechanical) and thrombus deposition and growth in regions of low wall shear stress (WSS). Laminar simulations are performed in a two-dimensional asymmetric sudden expansion geometry and compared with in vitro thrombus size data collected using whole bovine blood. Additionally, the predictive power of the model is tested in a flow cell containing a series of symmetric sudden expansions and contractions. Thrombi form in the low WSS area downstream of the asymmetric expansion and grow into the nearby recirculation region, and thrombus height and length largely remain within 95 % confidence intervals calculated from the in vitro data for 30 min of blood flow. After 30 min, predicted thrombus height and length are 0.94 and 4.32 (normalized by the 2.5 mm step height). Importantly, the model also correctly predicts locations of thrombus deposition observed in the in vitro flow cell of expansions and contractions. As the simulation results, which rely on a greatly reduced model of the thrombotic network, are still able to capture the macroscopic behavior of the full network, the model shows promise for timely predictions of device-induced thrombosis toward optimizing and expediting the device development process.

Continuous and Pulsatile Pediatric Ventricular Assist Device Hemodynamics with a Viscoelastic Blood Model.

To investigate the effects of pulsatile and continuous pediatric ventricular assist (PVAD) flow and pediatric blood viscoelasticity on hemodynamics in a pediatric aortic graft model. Hemodynamic parameters of pulsatility, along with velocity and wall shear stress (WSS), are analyzed and compared between Newtonian and viscoelastic blood models at a range of physiological pediatric hematocrits using computational fluid dynamics. Both pulsatile and continuous PVAD flow lead to a decrease in pulsatility (surplus hemodynamic energy, ergs/cm(3)) compared to healthy aortic flow but with continuous PVAD pulsatility up to 2.4 times lower than pulsatile PVAD pulsatility at each aortic outlet. Significant differences are also seen between the two flow modes in velocity and WSS. The higher velocity jet during systole with pulsatile flow leads to higher WSSs at the anastomotic toe and at the aortic branch bifurcations. The lower velocity but continuous flow jet leads to a much different flow field and higher WSSs into diastole. Under a range of physiological pediatric hematocrit (20-60%), both velocity and WSS can vary significantly with the higher hematocrit blood model generally leading to higher peak WSSs but also lower WSSs in regions of flow separation. The large decrease in pulsatility seen from continuous PVAD flow could lead to complications in pediatric vascular development while the high WSSs during peak systole from pulsatile PVAD flow could lead to blood damage. Both flow modes lead to similar regions prone to intimal hyperplasia resulting from low time-averaged WSS and high oscillatory shear index.

Hemodynamics in a Pediatric Ascending Aorta Using a Viscoelastic Pediatric Blood Model.

Congenital heart disease is the leading cause of infant death in the United States with over 36,000 newborns affected each year. Despite this growing problem there are few mechanical circulatory support devices designed specifically for pediatric and neonate patients. Previous research has been done investigating pediatric ventricular assist devices (PVADs) assuming blood to be a Newtonian fluid in computational fluid dynamics (CFD) simulations, ignoring its viscoelastic and shear-thinning properties. In contrast to adult VADs, PVADs may be more susceptible to hemolysis and thrombosis due to altered flow into the aorta, and therefore, a more accurate blood model should be used. A CFD solver that incorporates a modified Oldroyd-B model designed specifically for pediatric blood is used to investigate important hemodynamic parameters in a pediatric aortic model under pulsatile flow conditions. These results are compared to Newtonian blood simulations at three physiological pediatric hematocrits. Minor differences are seen in both velocity and wall shear stress (WSS) during early stages of the cardiac cycle between the Newtonian and viscoelastic models. During diastole, significant differences are seen in the velocities in the descending aorta (up to 12%) and in the aortic branches (up to 30%) between the two models. Additionally, peak WSS differences are seen between the models throughout the cardiac cycle. At the onset of diastole, peak WSS differences of 43% are seen between the Newtonian and viscoelastic model and between the 20 and 60% hematocrit viscoelastic models at peak systole of 41%.

The impact of yoga on atrial fibrillation: A review of The Yoga My Heart Study.

Atrial fibrillation is a common arrhythmia affecting thousands of individuals worldwide. It is a conduction disorder that causes the heart to beat irregularly and rapidly. There are a few medical approaches to manage this costly health care burden: antiarrhythmics to maintain normal sinus rhythm, beta blockers to achieve rate control while allowing atrial fibrillation to persist, and electro-physiologic intervention for rate and rhythm control. These treatments can be costly and are not without side effects. Yoga, an intervention that is available to people worldwide, has shown some promise in combating this widespread heart disorder.

Sex- and gender-specific research priorities in cardiovascular resuscitation: proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Resuscitation Research Workgroup.

Significant sex and gender differences in both physiology and psychology are readily acknowledged between men and women; however, data are lacking regarding differences in their responses to injury and treatment and in their ultimate recovery and survival. These variations remain particularly poorly defined within the field of cardiovascular resuscitation. A better understanding of the interaction between these important factors may soon allow us to dramatically improve outcomes in disease processes that currently carry a dismal prognosis, such as sudden cardiac arrest. As part of the 2014 Academic Emergency Medicine consensus conference "Gender-Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes," our group sought to identify key research questions and knowledge gaps pertaining to both sex and gender in cardiac resuscitation that could be answered in the near future to inform our understanding of these important issues. We combined a monthly teleconference meeting of interdisciplinary stakeholders from largely academic institutions with a focused interest in cardiovascular outcomes research, an extensive review of the existing literature, and an open breakout session discussion on the recommendations at the consensus conference to establish a prioritization of the knowledge gaps and relevant research questions in this area. We identified six priority research areas: 1) out-of-hospital cardiac arrest epidemiology and outcome, 2) customized resuscitation drugs, 3) treatment role for sex steroids, 4) targeted temperature management and hypothermia, 5) withdrawal of care after cardiac arrest, and 6) cardiopulmonary resuscitation training and implementation. We believe that exploring these key topics and identifying relevant questions may directly lead to improved understanding of sex- and gender-specific issues seen in cardiac resuscitation and ultimately improved patient outcomes.

In vitro quantification of time dependent thrombus size using magnetic resonance imaging and computational simulations of thrombus surface shear stresses.

Thrombosis and thromboembolization remain large obstacles in the design of cardiovascular devices. In this study, the temporal behavior of thrombus size within a backward-facing step (BFS) model is investigated, as this geometry can mimic the flow separation which has been found to contribute to thrombosis in cardiac devices. Magnetic resonance imaging (MRI) is used to quantify thrombus size and collect topographic data of thrombi formed by circulating bovine blood through a BFS model for times ranging between 10 and 90 min at a constant upstream Reynolds number of 490. Thrombus height, length, exposed surface area, and volume are measured, and asymptotic behavior is observed for each as the blood circulation time is increased. Velocity patterns near, and wall shear stress (WSS) distributions on, the exposed thrombus surfaces are calculated using computational fluid dynamics (CFD). Both the mean and maximum WSS on the exposed thrombus surfaces are much more dependent on thrombus topography than thrombus size, and the best predictors for asymptotic thrombus length and volume are the reattachment length and volume of reversed flow, respectively, from the region of separated flow downstream of the BFS.

Platelet adhesion to polyurethane urea under pulsatile flow conditions.

Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s(-1). The aim of the current work is to determine the properties of platelet adhesion to the polyurethane urea surface as a function of time-varying shear exposure. A rotating disk system was used to study the influence of steady and pulsatile flow conditions (e.g., cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments were conducted with the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk was rotated in platelet-rich bovine plasma for 2 h, with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow was found to decay exponentially with increasing shear rate. Adhesion levels were found to depend upon peak platelet flux and shear rate, regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices.

The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro, a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s-1, which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.