Kenneth C. Butler

HeartMate II Left Ventricular Assist System: From Concept to First Clinical Use

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Development of the Nimbus/University of Pittsburgh innovative ventricular assist system ☆

BACKGROUND Nimbus Inc, and the University of Pittsburghs McGowan Center for Artificial Organ Development have been collaborators on rotary blood pump technology initiatives since 1992. Currently, a major focus is an innovative ventricular assist system (IVAS) that features an implantable, electrically powered axial flow blood pump. In addition to the blood pump, a major development item is the electronic controller and the control algorithm for modulating pump speed in response to varying physical demand. METHODS Methods used in developing the IVAS include computational fluid dynamic modeling of the pumps interior flow field, flow visualization of the flow field using laser-based imaging, computer simulation of blood pump-physiological interactions, vibroaccoustic monitoring, and an extensive in vivo test program. RESULTS Results to date, which are presented below, include successful in vivo tests of blood pumps with blood-immersed bearings, and feasibility demonstration of vibroacoustic monitoring in this application. CONCLUSIONS This unique blend of industrial experience and technologies with the University-based Research and Development Center has greatly enhanced the progress made on this IVAS project.

Development of an axial flow blood pump LVAS.

Nimbus, Inc., (Rancho Cordova, CA) and the University of Pittsburgh (Pittsburgh, PA) are collaborating to develop an implantable rotary blood pump that can be used as a left ventricular assist system (LVAS). The short-term goal of this project is to show that an LVAS based on this pump can operate safely and reliably during chronic implantations in animals. Work conducted to date includes in vitro testing of hydraulic performance, hemolysis, endurance demonstration, and flow visualization. Results indicate that the pump is capable of generating an output of up to 10 L/min at physiologic pressures. Associated electrical power to drive these pumps is in the range of 6-10 watts. One integrated pump was placed in a mock flow loop and operated continuously at a fixed speed (10,000 rpm), pressure (100 mmHg), and flow rate (6 L/min) for 90 days with no apparent difficulty. In vitro hemolysis test results have consistently ranged between 3-6 g of liberated hemoglobin/day, which is an acceptable range for chronic use. Two in vivo trials of 7 and 14 days were performed using calves, after which tests have been done using sheep as the animal model. Five short-term sheep experiments have been conducted with good results. Future studies will include implantations in sheep of 3 months duration.

Dynamic systemic vascular resistance in a sheep supported with a Nimbus AxiPump.

Changes in systemic vascular resistance (SVR) in response to diminished pulse perfusion were analyzed over a dynamic range of flow conditions. An axial flow LVAD (Nimbus AxiPump, Rancho Cordova, CA) was implanted in a sheep for 28 days, during which time SVR was determined over several conditions of posture and excitability. Total arterial resistance (TR) was calculated dynamically as an index of SVR by analysis of pump flow in diastole, and systemic pressure estimated from the characteristic pressure-flow-speed relation of the AxiPump. TR was evaluated over a range of flow rates, including maximum flow--for which the pressures and flows were essentially nonpulsatile. Throughout the course of support, and independent of pulsatility, TR dropped when the sheep stood and was significantly lower than that in the sitting position (P < 0.01). Response to excitement followed the same trend: TR was significantly higher during agitation than during normal temper (P < 0.01). In spite of changes in pulse pressure and flow rate, SVR changes occurred according to expected physiologic responses for pulsatile perfusion. Because pump flow and pressure are sensitive to afterload, the results of these studies suggest that pump speed control must compensate for changes in SVR to maintain acceptable perfusion.

The Cleveland Clinic-Nimbus total artificial heart: Design and in vitro function

We describe the design and in vitro testing of the Cleveland Clinic-Nimbus electrohydraulic permanent total artificial heart as it nears completion of development. The total artificial heart uses an electric motor and hydraulic actuator to drive two diaphragm-type blood pumps. The interventricular space contains the pump control electronics and is vented to an air-filled compliance chamber. Pericardial tissue valves and biolized blood-contacting surfaces potentially eliminate the need for anticoagulation. In vitro studies on a mock circulatory circuit demonstrated preload-sensitive control of pump output over the operating range of the blood pump: 70 to 160 beats/min and 5 to 9.6 L/min at right and left atrial pressures of 1.0 to 7.0 mm Hg and 5.0 to 12.0 mm Hg, respectively. The pump output was found to be insensitive to afterload over a range of 15 to 40 mm Hg mean pulmonary artery pressure and 60 to 130 mm Hg mean systemic pressure. The left master alternate control mode balanced the ventricular outputs during simulated bronchial artery shunting of up to 20% of cardiac output. A 10% to 15% right-pump, stroke-volume limiter balanced ventricular outputs during maximum output of 9.6 L/min. In response to a sustained increase in systemic venous return, the pump increased output by 2 L/min (29%) in 35 seconds. Thus the Cleveland Clinic-Nimbus total artificial heart meets the National Heart, Lung, and Blood Institute hemodynamic performance goals for devices being developed for permanent heart replacement. The biolized blood-contacting surfaces should decrease the risk of thromboembolism associated with circulatory assist devices.

A Computational and Experimental Comparison of Two Outlet Stators for the Nimbus LVAD

Two designs of an outlet stalor for the Nimbus axial flow left ventricular assist device (LVAD) are analyzed at nominal operating conditions. The original stator assembly (Design 1) has significant flow separation and reversal. A second stator assembly (Design 2) replaces the original tubular outer housing with a converging-diverging throat section with the intention of locally improving the fluid dynamics. Both stator designs are analyzed using computational fluid dynamics (CFD) analysis and experimental particle imaging flow visualization (PIFV). The computational and experimental methods indicate: 1) persistent regions of flow separation in Design 1 and improved fluid dynamics in Design 2; 2) blade-to-blade velocity fields that are well organized at the blade tip yet chaotic at the blade hub for both designs; and 3) a moderate decrease in pressure recovery for Design 2 as compared with Design 1. The CFD analysis provides the necessary insight to identify a subtle, localized flow acceleration responsible for the decreased hydraulic efficiency of Design 2. In addition, the curiously low thrombogenicity of Design 1 is explained by the existence of a three-dimensional unsteady vortical flow structure that enhances boundary advection. ASAIO Journal 1999; 45:328–333.

In vivo evaluation of the Nimbus axial flow ventricular assist system. Criteria and methods.

Continuing in vivo trials are being conducted at the University of Pittsburgh using the Nimbus axial flow blood pump (AxiPump). To date, 14 sheep experiments have been performed to address several issues related to short-term support. Six acute experiments (< 6 hr) have been performed to assess hemodynamics related to speed regulation and to determine anatomic placement of the pump and cannulae. Eight short-term survival studies lasting up to 6 days have been performed to evaluate biocompatibility and system reliability, and to establish clinical management protocols. The AxiPump has been used as a left ventricular assist device (LVAD), right ventricular assist device (RVAD), and biventricular assist device (BiVAD) with left ventricular and right atrial cannulation. The AxiPump has demonstrated the ability to assume complete support of either the pulmonary or systemic circulation, or both. We have determined that sufficient surgical access may be obtained through left lateral thoracotomy for both LVAD and RVAD insertion. In the absence of post operative anticoagulation therapy, we have detected subclinical renal cortical infarctions in 6 of 8 short-term animals. Thrombus deposition has been observed at the ventricular cannula tip in 4 of 8 cases--necessitating design changes. Two short-term experiments have been terminated because of bleeding--one due to inflow cannula obstruction and one due to cannula failure. Plasma free hemoglobin levels were all below 15 mg/dl, except for one case complicated by inflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system.

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

Progress in Cleveland Clinic-Nimbus total artificial heart development

A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses electrohydraulic energy conversion and an automatic left master-alternate mode control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major organ and blood cell function. Post-operative suppression of platelet aggregation recovered by the second post-operative week. The gelatin-coated pump surface generally was clean without any anticoagulants and free from infection. Embolism, which occurred in two cases, was caused by complications attributable to fungal infection in a Dacron graft and by thrombus formed around a jugular vein catheter. A system with a hybridized microcircuit controller in the interventricular space has been tested successfully in the three most recent cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat effects were confined to the tissues immediately adjacent to the hottest spots. The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The transcutaneous energy transmission system and the internal battery functioned well as designed in the most recent animal implant.

Low bearing wear in explanted HeartMate II left ventricular assist devices after chronic clinical support.

The primary objective of this study was to evaluate bearing wear during clinical use of the HeartMate II (HMII) left ventricular assist device. Bearings obtained from HMII pumps explanted after clinical use in the Destination Therapy and Bridge to Transplantation clinical trials were analyzed for wear using surface profilometry. Geometric profile variations measured on the inlet bearing ball were used to calculate the wear. Bearing wear was normalized to the total pump support duration to obtain an annualized bearing wear rate. Bearing life was estimated assuming a linear wear rate, as the time to reach a wear limit of 25 µm, which includes a 3× safety factor, to ensure that there is no contact between the rotor blades and the blood bore housing. One hundred and eighty-three bearings from left ventricular assist devices implanted in 181 patients were analyzed. Average age of the patients was 56.3 ± 14.6 years, 76% were male, 46% had an ischemic etiology of heart failure. Mean support duration for the pumps was 363 ± 349 days (median: 238, range: 1–1,621 days). Sixty pumps (33%) were explanted at heart transplantation, 20 (11%) after device replacement, 6 (3%) for ventricular recovery, 94 (51%) after patient death, and 3 (2%) were explanted for other reasons. Mean bearing wear was 0.59 ± 0.37 µm (median: 0.46 µm [5–95% interval: 0.25–1.48]). The median bearing wear rate for patients supported for at least 1 year was 0.30 [5–95% interval: 0.09–0.94] µm/yr. The 5–95% limits of the bearing wear rate corresponded to an estimated bearing life between 27 and 269 years. The pump having the highest bearing wear rate (1.46 µm/yr) had an estimated bearing life of at least 17 years. HMII bearing wear is extremely small, with an estimated bearing life well in excess of 17 years; it is not a limiting factor for long-term support with the HMII left ventricular assistive system.