Stephen Benefit

Development of a small implantable right ventricular assist device.

The purpose of this program is to design, develop, and clinically evaluate a new, implantable right ventricular assist device (RVAD) that can be used as a component of an implantable biventricular assist device for patients with severe biventricular heart failure. The initial phase of this program resulted in a prototype RVAD, named DexAide, a modified version of the CorAide left ventricular assist device. In vitro testing was performed in a stand-alone circuit and in a true RVAD mode to evaluate pump performance. Pump flow and power were measured under various afterload and pump speed conditions. The pump performance requirements of 2 to 6 l/min and a pressure rise of 20 to 60 mm Hg were successfully met with pump speeds between 1,800 and 3,200 rpm. The nominal design point of 4 l/min and 40 mm Hg pressure rise was achieved at 2,450 ± 70 rpm with a power consumption of 3.0 ± 0.2 W. The initial in vitro testing met the design criteria for the new DexAide RVAD. Initial in vivo testing is under way, which will be followed by preclinical readiness testing and a pilot clinical trial in this 5-year program.

Development of DexAide right ventricular assist device: update II.

The DexAide right ventricular assist device (RVAD) is a magnetically and hydrodynamically levitated implantable centrifugal pump. Recent progress includes 1) redesign of the inflow/outflow conduits, which yielded two successful 3-month experiments, 2) development of alternative journal bearing materials, and 3) completion of an 18-month duration of in vitro endurance testing. Verification testing of the RVAD electronics has been completed, and a prototype biventricular assist device (BVAD) system has been tested. Acute DexAide/CorAide BVAD implantations via median sternotomy in two calves documented BVAD control algorithms and anatomical fit. A drug-induced chronic calf heart failure model, currently under development in our laboratory, resulted in a successful BVAD implantation in a calf with heart failure. Our future plans are to complete in vitro and in vivo validation of alternative bearing materials, perform preclinical DexAide in vivo and in vitro reliability studies, and obtain Food and Drug Administration (FDA) approval for an Investigational Device Exemption to conduct a clinical pilot study. In conclusion, two successful 3 month in vivo experiments and an 18-month in vitro endurance test were completed. After final bearing material selection, the DexAide design will be “frozen” so that preclinical systems can be manufactured. BVAD experiments using a chronic heart failure model are in progress.

Acute in vivo evaluation of an implantable continuous flow biventricular assist system.

An implantable biventricular assist device offers a considerable opportunity to save the lives of patients with combined irreversible right and left ventricular failure. The purpose of this study was to evaluate the hemodynamic and physiologic performance of the combined implantation of the CorAide™ left ventricular assist device (LVAD) and the DexAide right ventricular assist device (RVAD). Acute hemodynamic responses were evaluated after simulating seven different physiological conditions in two calves. Evaluation was performed by fixing the speed of one individual pump and increasing the speed of the other. Under all conditions, increased LVAD or RVAD speed resulted in increased pump flow. The predominant pathophysiologic effect of independently varying DexAide and CorAide pump speeds was that the left atrial pressure was very sensitive to increasing RVAD speed above 2,400 rpm, whereas the right atrial pressure demonstrated much less sensitivity to increasing LVAD speed. An increase in aortic pressure and RVAD flow was observed while increasing LVAD speed, especially under low contractility, ventricular fibrillation, high pulmonary artery pressure, and low circulatory blood volume conditions. In conclusion, a proper RVAD-LVAD balance should be maintained by avoiding RVAD overdrive. Additional studies will further investigate the performance of these pumps in chronic animal models.

Development of the DexAide right ventricular assist device inflow cannula.

Cannula design and cannulation site can pose major limitations to chronic pump implantations in animal studies. The aim of this study was to evaluate the biocompatibility of various inflow cannula designs for the DexAide right ventricular assist device (RVAD). The DexAide RVAD was implanted for intended durations of 14, 30, or 90 days in 19 animals (mean 20 ± 11 days). Seven inflow cannula designs were evaluated: angled titanium conduit with caged tip (two cases); flexible polyurethane coated polyvinyl chloride (PVC) tube (one case); open ended titanium (one case); a titanium cannula with a flange (six cases); a cannula with a gelatin coated flange (five cases); a cannula with an angled flange (one case); and open ended titanium with two side holes (three cases). The open ended titanium inflow cannula with two side holes positioned through the diaphragmatic surface of the right ventricle (RV) via a right thoracotomy showed good biocompatibility for the chronic animal study. Other cannulae inserted into the infundibular portion of the RV via a left thoracotomy showed significant depositions. Gelatin coated inflow cannula had the advantage to prevent tissue growth around the inflow cannula. The DexAide RVAD pump itself showed good biocompatibility, although nonadherent depositions originating from the inflow cannulae were captured onto the primary impeller blades.

Progress in the development of the DexAide right ventricular assist device.

The DexAide right ventricular assist device (RVAD) is an implantable centrifugal pump modified from the CorAide left ventricular assist device. As previously published, in vitro performance testing of the DexAide RVAD has met design criteria, and the nominal operating condition of 4 l/min and 20 mm Hg pressure rise was achieved at 2,000 rpm, with a power consumption of 1.9 watts. In vivo studies in 14 calves have demonstrated acceptable hemodynamic characteristics. The calf inflow cannula design is still evolving to minimize depositions on the cannula observed in most experiments. Fitting studies were performed in 5 cadavers and 2 patients to reconfigure the cannulae for use in humans. The design and development of external electronics have been completed for the stand-alone RVAD system, and verification tests are under way in preparation for preclinical tests. Work on the external electronics design for the biventricular assist system is ongoing. In conclusion, the initial in vitro and in vivo studies have demonstrated acceptable hemodynamic characteristics of the DexAide RVAD. The design and development of the external electronic components for the stand-alone RVAD system have been completed. The calf inflow cannula is being redesigned, and chronic in vivo tests are under way.

In Vivo Biocompatibility Evaluation of a New Resilient, Hard-Carbon, Thin-Film Coating for Ventricular Assist Devices

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Hearts (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

Initial In Vivo Evaluation of the DexAide Right Ventricular Assist Device

Despite the increasing use of left ventricular assist devices for patients with end-stage congestive heart failure, no implantable, centrifugal right ventricular assist devices (RVADs) are available for those patients with significant right ventricular failure. The DexAide RVAD was developed to provide an implantable RVAD option to surgeons. The aim of this study was to evaluate pump performance in an acute in vivo model. The DexAide RVAD, developed as a modified CorAide left ventricular assist device, was implanted between the right ventricle and the pulmonary artery in four healthy calves. Pump speed was varied from 1800 rpm to 3600 rpm. RVAD performance was analyzed acutely at baseline and under conditions of low circulating volume, high contractility, high pulmonary arterial pressure, vasodilation, and low contractility. Pump flow was well maintained even under conditions of high pulmonary arterial pressure and vasodilation, with the exception of low circulating volume. Under all conditions, pulmonary arterial pressures were not affected by changing pump speed. The DexAide RVAD demonstrated acceptable hemodynamic characteristics for use as an implantable RVAD in the initial acute studies. Further studies are ongoing to examine the biocompatibility of the pump under chronic conditions.

Use of Zirconia Ceramic in the DexAide Right Ventricular Assist Device Journal Bearing

Our aim was to evaluate the potential use of zirconium oxide (zirconia) as a blood journal bearing material in the DexAide right ventricular assist device. The DexAide titanium stator was replaced by a zirconia stator in several blood pump builds, without changing the remaining pump hardware components. In vitro pump performance and efficiency were evaluated at a predetermined pump speed and flow. Motor power consumption decreased by 20%, and DexAide battery life was extended to over 12 h on two fully charged batteries. The zirconia stator was also successfully evaluated in a severe start/stop test pre- and postexposure of the zirconia to accelerated simulated biologic aging. This studys outcomes indicated the advantages of zirconia as an alternate journal bearing material for the DexAide device.

In Vivo Evaluation of Zirconia Ceramic in the DexAide Right Ventricular Assist Device Journal Bearing

Zirconia is a ceramic with material properties ideal for journal bearing applications. The purpose of this study was to evaluate the use of zirconium oxide (zirconia) as a blood journal bearing material in the DexAide right ventricular assist device. Zirconia ceramic was used instead of titanium to manufacture the DexAide stator housing without changing the stator geometry or the remaining pump hardware components. Pump hydraulic performance, journal bearing reliability, biocompatibility, and motor efficiency data of the zirconia stator were evaluated in six chronic bovine experiments for 14-91 days and compared with data from chronic experiments using the titanium stator. Pump performance data including average in vivo pump flows and speeds using a zirconia stator showed no statistically significant difference to the average values for 16 prior titanium stator in vivo studies, with the exception of a 19% reduction in power consumption. Indices of hemolysis were comparable for both stator types. Results of coagulation assays and platelet aggregation tests for the zirconia stator implants showed no device-induced increase in platelet activation. Postexplant evaluation of the zirconia journal bearing surfaces showed no biologic deposition in any of the implants. In conclusion, zirconia ceramic can be used as a hemocompatible material to improve motor efficiency while maintaining hydraulic performance in a blood journal bearing application.