Development of a totally implantable pulsatile centrifugal pump as a ventricular assist device

The Taita No. 1 ventricular assist device (T-VAD) is a totally implantable pulsatile impeller centrifugal pump driven by a magnetically suspended motor. The flow can achieve 2.01 +/- 0.17 L/min against a pressure of 100 mm Hg under 0.266 +/- 0.017 amp and 13.55 +/- 0.41 voltage. The speed was around 3,500 rpm. It consumed less than 6 W of power, resulting in less heat production and mechanical bearing complications. The impeller vane was designed to have both radial and axial curves according to the stream surface and stream lines to reduce thrombosis and hemolysis. Eight calves weighing 80 to 100 kg (mean 87 +/- 12 kg) were used for experiments. With the calves under general anesthesia, left posterolateral thoracotomy was performed to connect the inflow tube with the atrial appendage and to anastomose the outflow tube with the descending aorta. The calves usually awoke and stood up within hours after discontinuation of anesthetics. The mean survival of the calves was 75 +/- 42 days (range 33-148 days). The terminations of experiments were mainly due to infection. During the course of pumping, no significant deterioration of liver or renal function was noted. The evaluation of serum samples from the implanted calves indicated that hemolysis was not associated with use of the T-VAD. The average daily free hemoglobin level was 8.08 +/- 3.05 mg/dl, which was less than the set limit of 20 mg/dl. The red blood cell and platelet count and hemoglobin of implanted animals were within the normal range. In our results, the T-VAD provided competent pulsatile function without severe blood damage or organ dysfunction.     

Assessing the calf pulmonary function during a long-term biventricular assist device study with a centrifugal blood pump

Pulmonary congestion due to inappropriate pump flow management is one major problem necessary to avoid during long-term biventricular assist device (BVAD) implantation. Our objective was to assess the effects of pulmonary arterial flow rate and flow rates of both (right and left) bypass pumps. Six healthy calves, which had been implanted with a BVAD system, were selected for this retrospective study. Pulmonary artery flows, both pump flow rates, oxygen saturation of the arterial blood, and pulmonary arterial pressures were assessed as parameters of pulmonary function as was routine clinical evaluation of respiratory rate and character and chest auscultation. The average pulmonary artery flow rate (PAF), systolic pressure of pulmonary artery (sPAP), and oxygen saturation were 148.8 ml/kg per min, 35.1 mm Hg, and 95.3%, respectively. Pulmonary dysfunction occurred in one case, in which the mean PAF, sPAP, and oxygen saturation were 169 ml/kg per min, 66.1 mm Hg, and 90.9%, respectively. The ratio for the right/left pump flow rate (R/L ratio) for the case having pulmonary dysfunction was 1.57 even though the ratio for the other cases was less than 1. Maintaining an R/L ratio less than 1 and/or PAF less than 160 ml/kg per min and PAP less than 50 mm Hg is recommended as the initial conditions to target to avoid pulmonary dysfunction during a BVAD implantation with a beating heart condition.     

Right ventricular failure after left ventricular assist device implantation: the need for an implantable right ventricular assist device

Right ventricular failure after implantation of a left ventricular assist device is an unremitting problem. Consideration of portal circulation is important for reversing liver dysfunction and preventing multiple organ failure after left ventricular assist device implantation. To achieve these objectives, it is imperative to maintain the central venous pressure as low as possible. A more positive application of right ventricular assistance is recommended. Implantable pulsatile left ventricular assist devices cannot be used as a right ventricular assist device because of their structure and device size. To improve future prospects, it is necessary to develop an implantable right ventricular assist device based on a rotary blood pump.     

Development status of Terumo implantable left ventricular assist system

We have been developing an implantable left ventricular assist system (T-ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long-term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long-term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long-term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.     

Performance characterization of a rotary centrifugal left ventricular assist device with magnetic suspension

Abstract:  The MiTiHeart (MiTiHeart Corporation, Gaithersburg, MD, USA) left ventricular assist device (LVAD), a third-generation blood pump, is being developed for destination therapy for adult heart failure patients of small to medium frame that are not being served by present pulsatile devices. The pump design is based on a novel, patented, hybrid passive/active magnetic bearing system with backup hydrodynamic thrust bearing and exhibits low power loss, low vibration, and low hemolysis. Performance of the titanium alloy prototype was evaluated in a series of in vitro tests with blood analogue to map out the performance envelop of the pump. The LVAD prototype was implanted in a calf animal model, and the in vivo pump performance was evaluated. The animal's native heart imparted a strong pulsatility to the flow rate. These tests confirmed the efficacy of the MiTiHeart LVAD design and confirmed that the pulsatility does not adversely affect the pump performance.     

Hemodynamic exercise response in calves with an implantable biventricular centrifugal blood pump

An implantable biventricular assist device (BVAD) has been developed at Baylor College of Medicine using 2 centrifugal blood pumps. The aim of this study was to investigate the exercise-reflex response during nonpulsatile biventricular assistance and to evaluate to which degree the autoregulation of the system would accommodate the changed hemodynamic situation during physical exercise. The Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half-Dexter) in a biventricular bypass fashion with native heart remaining. Allowing a 10 day convalescence, 2 animals were subjected to incremental exercise tests. The speed of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with increments of 0.2 mph every 3 min. During the exercise the pump flows were maintained at a fixed rate (6.93 +/- 0.01 L/min for the left ventricular assist device and 5.36 +/- 1.44 L/min for the right ventricular assist device). Hemodynamic parameters and pump performance were recorded continuously. The cardiac output (CO) and heart rate (HR) increased significantly during the exercise. CO increased from 11.1 +/- 0.3 to 13.1 +/- 0.4 L/min, and HR increased from 99 +/- 7.1 to 114 +/- 2.8 bpm, respectively. Mean aortic pressure, central venous pressure, and left arterial pressure did not change significantly. Also, no change was observed for the left and right pump flows. This totally implantable BVAD showed excellent long-term performance without any mechanical problems. It is feasible to operate without impairment under physical activity. However, the natural heart dominated the hemodynamic response during exercise under BVAD support. The left and the right pump flows did not increase spontaneously with exercise. We therefore conclude that a servo CO control system is necessary to regulate pump flows even during moderate exercise.     

Right ventricular assist system feedback flow control parameter for a rotary blood pump

At least 25-30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate.     

In Vivo Evaluation of the Miniaturized Gyro Centrifugal Pump as an Implantable Ventricular Assist Device

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 ± 0.57 L/min, and input power of 6.16 ± 0.49 W, and the inside temperature of the actuator of 43.5 ± 0.52°C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.     

Physiologic analysis of cardiac cycle in an implantable impeller centrifugal left ventricular assist device

The purpose of this study was to determine the physiologic relationship between the cardiac cycle and the nonpulsatile impeller centrifugal Taita No.1 left ventricular assist device (T-LVAD) in a chronic animal study. The relationship of the cardiac cycle, pump flow, aortic pressure, left ventricle pressure, and pump power were analyzed by 5 phases in 4 stages. The isovolumetric ventricular phase is from mitral valve closure (MVC) to aortic valve opening (AVO) and is called Stage 1. The ejection phase is from AVO to aortic valve closure (AVC) and is called Stage 2. The isovolumetric relaxation phase is from AVC to MVC and is called Stage 3. The passive filling and atrial contraction phase is from MVC to mitral valve opening (MVO) and called Stage 4. Based on evidence from the physiologic volume change of the left ventricle, the change of pump flow of the T-LVAD in a cardiac cycle by variable voltages of pump control was evaluated using animal models. After left posteriolateral thoracotomy via the fifth intercostal space under general anesthesia, the nonpulsatile centrifugal T-LVAD was implanted into 2 healthy calves. The inflow of the T-LVAD was inserted into the left ventricle through the mitral valve via the left atrial appendage. The arterial blood pressure waveform was measured and recorded on the outflow of the T-LVAD. The 4 phases of a cardiac cycle were defined as MVC-AVO (Stage 1), AVO-AVC (Stage 2), AVC-MVO (Stage 3) and MVC-MVO (Stage 4) according to the outflow pressure of the outflow of the T-LVAD and differential pressure between the outflow and inflow of the T-LVAD. We carried out the real-time waveform measurement for electrocardiogram, the outflow pressure, the T-LVAD flow and the speed, as well as open loop and constant voltage (V). In a cardiac cycle, the sensing current of the T-LVAD was inverse to the speed. The flow of the T-LVAD at the 4 stages was measured individually and analyzed with different control voltages from 10 to 18 V. The highest flow ratio of MVC-AVC/AVC-MVC was noted when the T-LVAD worked on 14 V. By using analysis methodology of the flow ratio of a cardiac cycle, the optimal physiologically effective control of the T-LVAD might be achieved.     

Real-time studies of the pivot bearings in the NEDO Gyro PI-710 centrifugal blood pump

The NEDO Gyro PI-710 centrifugal pump (Gyro PI-710 pump) incorporates a double pivot bearing system of which the male pivot and female bearings are fabricated from Al2O3 ceramic and ultrahigh molecular weight polyethylene. The top female bearing is a critical component because the impeller is levitated by hydraulic force and is maintained in the top contact position. A long-term in vitro examination of the pivot bearings was conducted using a biventricular assist model. In 7 animal experiments, the depth change of the top female bearing was examined. Animal experiments up to 90 days revealed that there was no noticeable depth increase in the top female bearing. According to the in vitro study, the life of the pivot bearings of the left and right pump was estimated to be approximately 3 and 7 years, respectively. Further improvement of this pivot bearing system is currently underway.     

The Heartmate III: design and in vivo studies of a maglev centrifugal left ventricular assist device

A compact implantable centrifugal left ventricular assist device (LVAD) (HeartMate III) featuring a magnetically levitated impeller is under development. The goal of our ongoing work is to demonstrate feasibility, low hemolysis, and low thrombogenicity of the titanium pump in chronic bovine in vivo studies. The LVAD is based on so-called bearingless motor technology and combines pump rotor, drive, and magnetic bearing functions in a single unit. The impeller is rotated (theta z) and levitated with both active (X, Y) and passive (Z, theta x, theta y) suspension. Six prototype systems have been built featuring an implantable titanium pump (69 mm diameter, 30 mm height) with textured blood contacting surfaces and extracorporeal electronics. The pumps were implanted in 9 calves (< or = 100 kg at implant) that were anticoagulated with Coumadin (2.5 < or = INR < or = 4.0) throughout the studies. Six studies were electively terminated (at 27-61 days), 1 study was terminated after the development of severe pneumonia and lung atelectasis (at 27 days) another study was terminated after cardiac arrest (at 2 days) while a final study is ongoing (at approximately 100 days). Mean pump flows ranged from 2 to 7 L/min, except for brief periods of exercise at 6 to 9 L/min. Plasma free hemoglobin ranged from 4 to 10 mg/dl. All measured biochemical indicators of end organ function remained within normal range. The pumps have met performance requirements in all 9 implants with acceptable hemolysis and no mechanical failures.     

Computational fluid dynamics analysis of a maglev centrifugal left ventricular assist device

The fluid dynamics of the Thoratec HeartMate III (Thoratec Corp., Pleasanton, CA, U.S.A.) left ventricular assist device are analyzed over a range of physiological operating conditions. The HeartMate III is a centrifugal flow pump with a magnetically suspended rotor. The complete pump was analyzed using computational fluid dynamics (CFD) analysis and experimental particle imaging flow visualization (PIFV). A comparison of CFD predictions to experimental imaging shows good agreement. Both CFD and experimental PIFV confirmed well-behaved flow fields in the main components of the HeartMate III pump: inlet, volute, and outlet. The HeartMate III is shown to exhibit clean flow features and good surface washing across its entire operating range.     

Antithrombogenicity evaluation of a centrifugal blood pump

The Gyro C1E3 pump was developed not only for cardiopulmonary bypass but also as a short-term assist device. The main purpose of this study was to examine the correlation between the thrombus formation factor and the Gyro C1E3 pumps. Seven pumps were implanted into 3 calves and evaluated for different periods of duration as a paracorporeal left ventricular assist device (LVAD). One pump was subjected to percutaneous cardiopulmonary support condition (PCPS) (total pressure head 500 mm Hg with a pump flow rate of 3 L/min). The anticoagulation treatment consisted of a continuous administration of heparin to maintain an activated clotting time (ACT) of 200-250 during the LVAD study and 250-300 during the PCPS study. After the experiment, the pumps were disassembled and examined. In cases where there were any blood-derived deposits inside the pumps, the dry weight of these thrombi that adhered to the bearing area of the pump was measured. A multiple correlation was attempted to speculate possible thrombus formation. The estimated dry weight of thrombi was calculated from pump flow rate, pumping day, motor speed, and activated clotting time. This equation was estimated dry weight of thrombi = 1.140 x pump flow rate -0.001 motor speed + 1.652 pumping time -0.041 x ACT + 2.198 R2 = 0.944. This study suggested that there was a possibility to calculate the amount of adhered thrombus formation from pump flow rate, motor speed, pumping day, and ACT.     

Development of normal-suction boundary control method based on inflow cannula pressure waveform for the undulation pump ventricular assist device

It is desirable to obtain the maximum assist without suction in ventricular assist devices (VADs). However, high driving power of a VAD may cause severe ventricle suction that can induce arrhythmia, hemolysis, and pump damage. In this report, an appropriate VAD driving level that maximizes the assist effect without severe systolic suction was explored. The target driving level was set at the boundary between low driving power without suction and high driving power with frequent suction. In the boundary range, intermittent mild suction may occur. Driving power was regulated by the suction occurrence. The normal-suction boundary control method was evaluated in a female goat implanted with an undulation pump ventricular assist device (UPVAD). The UPVAD was driven in a semipulsatile mode with heartbeat synchronization control. Systolic driving power was adjusted using a normal-suction boundary control method developed for this study. We confirmed that driving power could be maintained in the boundary range. Occurrences of suction were evaluated using the suction ratio. We defined this ratio as the number of suction occurrences divided by the number of heartbeats. The suction ratio decreased by 70% when the normal-suction boundary control method was used.     

Development of totally implantable pulsatile biventricular assist device

Approximately 10% to 15% of all patients implanted with left ventricular assist devices (LVADs) have required right heart support with another device. The necessity of aggressive biventricular support has already been proposed. Therefore, the totally implantable biventricular assist device (BVAD) was developed. The width of the BVAD main body was 87 mm, the thickness 67 mm, and the height 106 mm, while the weight was 785 g. The automatic control algorithm was developed to prevent lung edema and atrial rupture.     

HeartQuest ventricular assist device magnetically levitated centrifugal blood pump

Improvements in implantable ventricular assist device (VAD) performance will be required to obtain patient outcomes that are comparable with those of heart transplantation. The HeartQuest VAD (WorldHeart, Oakland, CA, U.S.A.) is an advanced device, with full magnetic suspension of the rotor, designed to address specific clinical shortcomings in existing devices and to maximize margins of safety and performance for an implantable assist device. The device dimensions are 35 x 75 mm, with a total weight of 440 g. The system was designed using extensive computer modeling of device function; a total of two iterations of device prototypes were built before building the clinical version. Animal study results have been very promising, with over 30 calf studies completed. Plasma-free hemoglobin levels returned to preoperative levels, and other hematology results were in the normal ranges. Highlights include clean surfaces seen in a 116-day experiment with no anticoagulation after day 43. Feasibility clinical trials are planned to start in 2006.     

Chronic evaluation of the Cleveland Clinic CorAide left ventricular assist system in calves

The Cleveland Clinic CorAide left ventricular assist system is based on a third-generation, implantable, centrifugal pump in which a rotating assembly is suspended fully. To evaluate chronic in vivo system performance and biocompatibility, the CorAide blood pump was implanted in 18 calves for either 1 month or 3 months. Hemodynamics were stable in all calves with a mean pump flow of 5.9 +/- 1.2 L/min and a mean systemic arterial pressure of 98 +/- 5 mm Hg. There were no incidences of bleeding, organ dysfunction, or mechanical failure in any of the 18 calves. Hemolysis occurred in only 1 calf due to outflow graft stenosis. Thrombus inside the pump, seen in 4 of the first 6 cases, was totally eliminated by a final redesign in the remaining cases, including the last 6 implants conducted without anticoagulation therapy. The CorAide blood pump demonstrated good biocompatibility and reliable, effective system performance.     

Centrifugal blood pump with a hydraulically-levitated impeller for a permanently implantable biventricular assist device

A permanently implantable biventricular assist device (BVAD) system has been developed with a centrifugal pump which is activated by a hydraulically-levitated impeller. The pump impeller floats hydraulically into the top contact position; this position prevents thrombus formation by creating a washout effect at the bottom bearing area, a common stagnant region. The pump was subjected to in vitro studies using a pulsatile mock circulation loop to confirm the impeller's top contact position and the swinging motion produced by the pulsation. Eleven in vivo BVAD studies confirmed that this swinging motion eliminated blood clot formation. Twenty-one pumps im-planted for up to three months did not reveal any thrombosis in the pumps or downstream organs. One exception was a right pump which was exposed to severe low flow due to the kinking of the outflow graft by the accidental pulling of the flow meter cable. Three ninety-day BVAD studies were achieved without thrombus formation.     

Numerical simulation of the pulsating catheter pump: A left ventricular assist device

The pulsating catheter (PUCA) pump, a left ventricular assist device, consists of a hydraulically or pneumatically driven membrane pump, extracorporeally placed and mounted to a valved catheter. The catheter is introduced into an easily accessible artery and positioned with its distal tip in the left ventricle. Blood is aspirated from the left ventricle during systole and ejected into the ascending aorta during diastole. A numerical model of the PUCA pump has been developed to determine the internal diameter of the PUCA pump catheter that allows a certain blood flow. The model considers a limitation of mechanical blood damage and determines the accompanying pressure and flow profile for driving the pump. For a flow of 5 L/min, a catheter with an internal diameter of at least 6. 95 mm is required. For 3 L/min, the minimal diameter is 5.50 mm. The latter catheter can be introduced in the axillary artery, the former via the aorta during an open thorax surgical procedure. To validate the numerical model, 2 different PUCA pump configurations were tested in vitro. Results showed a good resemblance between model and in vitro behavior of the PUCA pump.     

Computational fluid dynamics design and analysis of a passively suspended Tesla pump left ventricular assist device

This article summarizes the use of computational fluid dynamics (CFD) to design a novel suspended Tesla left ventricular assist device. Several design variants were analyzed to study the parameters affecting device performance. CFD was performed at pump speeds of 6500, 6750, and 7000 rpm and at flow rates varying from 3 to 7 liters per minute (LPM). The CFD showed that shortening the plates nearest the pump inlet reduced the separations formed beneath the upper plate leading edges and provided a more uniform flow distribution through the rotor gaps, both of which positively affected the device hydrodynamic performance. The final pump design was found to produce a head rise of 77 mm Hg with a hydraulic efficiency of 16% at the design conditions of 6 LPM through flow and a 6750 rpm rotation rate. To assess the device hemodynamics the strain rate fields were evaluated. The wall shear stresses demonstrated that the pump wall shear stresses were likely adequate to inhibit thrombus deposition. Finally, an integrated field hemolysis model was applied to the CFD results to assess the effects of design variation and operating conditions on the device hemolytic performance.