Shaun T. Snyder

Biocompatibility Assessment of the First Generation PediaFlow Pediatric Ventricular Assist Device

The PediaFlow pediatric ventricular assist device is a miniature magnetically levitated mixed flow pump under development for circulatory support of newborns and infants (3-15 kg) with a targeted flow range of 0.3-1.5 L/min. The first generation design of the PediaFlow (PF1) was manufactured with a weight of approximately 100 g, priming volume less than 2 mL, length of 51 mm, outer diameter of 28 mm, and with 5-mm blood ports. PF1 was evaluated in an in vitro flow loop for 6 h and implanted in ovines for three chronic experiments of 6, 17, and 10 days. In the in vitro test, normalized index of hemolysis was 0.0087 ± 0.0024 g/100L. Hemodynamic performance and blood biocompatibility of PF1 were characterized in vivo by measurements of plasma free hemoglobin, plasma fibrinogen, total plasma protein, and with novel flow cytometric assays to quantify circulating activated ovine platelets. The mean plasma free hemoglobin values for the three chronic studies were 4.6 ± 2.7, 13.3 ± 7.9, and 8.8 ± 3.3 mg/dL, respectively. Platelet activation was low for portions of several studies but consistently rose along with observed animal and pump complications. The PF1 prototype generated promising results in terms of low hemolysis and platelet activation in the absence of complications. Hemodynamic results validated the magnetic bearing design and provided the platform for design iterations to meet the objective of providing circulatory support for young children with exceptional biocompatibility.

In Vitro Evaluation of Multiobjective Hemodynamic Control of a Heart-Assist Pump

Ventricular assist devices now clinically used for treatment of end-stage heart failure require responsive and reliable hemodynamic control to accommodate the continually changing demands of the body. This is an essential ingredient to maintaining a high quality of life. To satisfy this need, a control algorithm involving a trade-off between optimal perfusion and avoidance of ventricular collapse has been developed. An optimal control strategy has been implemented in vitro that combines two competing indices: representing venous return and prevalence of suction. The former is derived from the first derivative of diastolic flow with speed, and the latter derived from the harmonic spectra of the flow signal. The responsiveness of the controller to change in preload and afterload were evaluated in a mock circulatory simulator using a HeartQuest centrifugal blood pump (CF4b, MedQuest Products, Salt Lake City, UT). To avoid the need for flow sensors, a state estimator was used, based on the back-EMF of the actuator. The multiobjective algorithm has demonstrated more robust performance as compared with controllers relying on individual indices.

Computational Fluid Dynamics-Based Design Optimization for an Implantable Miniature Maglev Pediatric Ventricular Assist Device

According to recently available statistics, approximately 36,000 new cases of congenital heart disease (CHD) occur each year [1]. Of these, several studies suggest that 9200, or 2.3 per 1000 live births, require invasive treatment or result in death in the first year of life [2]. The very limited options available to treat ventricular failure in these infants and young children have motivated us to develop the PediaFlow® ventricular assist system, which features a miniature rotodynamic blood pump having a magnetically levitated impeller and streamlined blood flow path. It is intended to be fully implantable, providing chronic (up to 6 months) circulatory support from birth to 2 years of age (3 kg to 15 kg body weight) with a nominal pressure rise of ∼100 mmHg for the flow range of 0.3 ∼ 2.3 L/min. By consideration of the hemodynamic requirements of this population [3], a nominal design point of 1.5 LPM with a target pressure rise of 100 mmHg was chosen for the design procedure. An important design requirement is the need for optimizing and miniaturizing the flow path to maximize hemodynamic performance while minimizing shear-stress induced blood trauma. A unique feature of magnetically levitated axial-flow blood pumps in general, and the PediaFlow® in particular, is a continuous annular fluid gap between rotor and housing. The dimensions of this gap are limited by the requirements for magnetic stiffness and motor efficiency, but must be sufficiently large to permit desired flow of blood and to avoid excessive shear stress and other flow disturbances. When shared with the impeller blades, a narrow annular flow gap generally necessitates greater rotational speeds to generate sufficient pressure rise and flow rate. However, the combination of small gap and high speed can be a formula for blood cell damage without sufficient optimization of flow path geometry including the blade profiles. Because of design tradeoffs such as these, which span across several subsystems of the PediaFlow® (electromagnetics, heat transfer, rotordynamics, etc.), our group has adopted a numerical, multidisciplinary approach to optimization. With regard to the flow path, we employed a CFD-based design optimization system developed by Wu et al. [4,5] that integrates a robust and flexible inverse blade design tool, automatic mesh generators, parameterized geometry models, and mathematical models of blood damage, integrated with commercial CFD packages. The PediaFlow® pump has evolved over four generations, denoted as PF1, PF2, PF3, and PF4. The PF3 evolved from its predecessor (PF2, [6]) by the realization that the rotor can operate above its rotordynamic critical rotational speed, which reduced the requirement for magnetic suspension stiffness. This, in turn, permitted a relatively larger annular gap; hence, smaller rotor diameter. Although PF3 demonstrated excellent in vivo biocompatibility over 72 days [7], adverse fluid–structure interaction caused an unstable operational range greater than 0.8 L/min and 18,000 revolutions per minute (rpm). This study describes the use of the aforementioned CFD-based design optimization tools for overcoming this limitation and thereby expanding the operating range and improving hydrodynamic performance in transitioning from the PF3 to a frozen PF4 design, as illustrated in Fig. ​Fig.11. Fig. 1 Two generations of the PediaFlow® ventricular assist device: PF3 and PF4. Cutaway (bottom) shows critical internal components of PF4.

Towards the development of a pediatric ventricular assist device.

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Childrens Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Modeling and Control of an Electromagnetic Variable Valve Actuation System

A novel electromechanical valve actuation system comprised of a linear actuator, valve, and energy storing cam/spring mechanism is presented. The system dynamics are modeled using Lagrangian mechanics, and a minimum-energy point-to-point optimal control problem is solved to find an optimal trajectory and input. The optimal input is used as a feedforward component in a transition controller to move the valve between the open and closed positions. Between transitions, a simple linear controller stabilizes the valve in the open and closed positions. A high-order model capturing the distributed nature of valve springs is used to validate state constraints related to positive cam/follower forces and a nonslip condition on the cam/follower. Finally, a prototype system is fabricated and tested with promising results.

Preclinical Performance of a Pediatric Mechanical Circulatory Support Device: The PediaFlow® Ventricular Assist Device

Objectives The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous‐flow pediatric ventricular assist device. The fourth‐generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. Methods Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh–led Consortium evaluated fourth‐generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). Results With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery–sized fourth‐generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. Conclusions Designated a Humanitarian Use Device for “mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery” by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth‐generation PediaFlow design to provide chronic pediatric cardiac support.

In-vitro evaluation of multi-objective hemodynamic control of heart-assist pump

Ventricular assist devices (VADs) now clinically used for treatment of end-stage heart failure require responsive and reliable control to accommodate the continually changing demands of the body. This is an essential ingredient to maintaining a high quality of life. To satisfy this need, a control algorithm involving a tradeoff between optimal perfusion and avoidance of suction is developed. An optimal control strategy has been implemented in-vitro that combines two competing indices: representing venous return and prevalence of suction. The former is derived from the first derivative of diastolic flow with speed, and the latter derived from the harmonic spectra of the flow signal. The responsiveness of the controller to change in preload and afterload were evaluated in a mock circulatory simulator using a maglev centrifugal blood pump (CF4b, MedQuest Products). To avoid the need for flow sensors, an estimator is utilized, based on the back-EMF of the actuator. The multi-objective controller has demonstrated more robust performance as compared to controllers relying on individual indices.