Ann Thorac Surg 2001;72:747-752
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump in calves
Yoshie Ochiai, MDa,
Leonard A.R. Golding, MDa,
Alex L. Massiello, MEBMEa,
Alexander L. Medvedev, PhDa,
Renee L. Gerhart, BSBMEa,
Ji-Feng Chen, BSa,
Masami Takagaki, MD, PhDa,
Kiyotaka Fukamachi, MD, PhDa
a Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
Accepted for publication May 16, 2001.
Address reprint requests to Dr Golding, Department of Biomedical Engineering/ND-20, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195
e-mail: golding{at}bme.ri.ccf.org
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Abstract
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Background. The Cleveland Clinic CorAide left ventricular assist system is based on a small implantable continuous-flow centrifugal blood pump with a completely suspended rotating assembly designed for long-term circulatory support (5 to 10 years).
Methods. Between June 1999 and August 2000, the CorAide blood pump was implanted in 10 calves for 1 month and in 3 calves for 3 months.
Results. The mean pump flow and arterial pressure were 6.1 ± 1.1 L/min and 97 ± 5 mm Hg, respectively. The mean plasma free-hemoglobin level after postoperative day 3 was 2.0 ± 1.8 mg/dL. Renal and hepatic function remained normal in all cases. There was no incidence of mechanical failure, hemolysis, bleeding, or systemic organ dysfunction in any of the cases. Significant findings at autopsy were limited to two cases of renal infarction, one of which was associated with an outflow graft infection.
Conclusions. The CorAide blood pump is easily implanted, reliable, nonhemolytic, and nonthrombogenic, positioning it as a leading third-generation, continuous-flow left ventricular assist system with a completely suspended rotor.
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Introduction
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The development of the CorAide implantable, continuous-flow centrifugal blood pump at the Cleveland Clinic Foundation was supported in part by a grant from the National Heart, Lung, and Blood Institute at the National Institutes of Health. Initial analytical input and design guidance were provided by a multi-institutional collaborative effort among the Cleveland Clinic Foundation and the Ohio Aerospace Institute (Cleveland, OH), NASA Glenn Research Center (Cleveland, OH) [1], The Ohio State University (Columbus, OH) [2, 3], and Mechanical Technology Inc (Albany, NY) [4]. The final development steps to achieve the refined simplicity of this left ventricular assist system (LVAS) were guided by the animal in vivo test results summarized herein. Intended uses are as bridge to heart transplantation [5, 6], alternative to heart transplantation [7], and bridge to recovery of the natural heart for patients in end-stage heart failure [8, 9].
The CorAide pump is a third-generation, implantable, continuous-flow device with a rotating assembly supported passively by magnetic forces and by a stable blood-lubricated fluid film bearing. It is designed to be simple, reliable, noncontacting, nonwearing, and nonthrombogenic. In this article we present the CorAide blood pump components, theory of operation, physiologic control algorithm, and results of in vivo animal testing.
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Material and methods
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CorAide device description
Component description and theory of operation
Detailed functional description of the CorAide pump components and theory of operation have been presented earlier [10, 11]. The current CorAide pump configuration (293 g), as shown in Figures 1A and 1B,consists of only three subassemblies : a volute housing, a rotating assembly, and a stator assembly. The cast titanium volute housing contains the threaded blood inlet and outlet ports. The pumping element is a cylindrical rotating assembly containing a permanent magnet ring and impeller vanes on each axial end of the assembly. The stator assembly contains the motor windings surrounded by a thin-walled titanium cylinder. This cylinder forms the post around which the rotating assembly spins and is the stationary part of the fluid film bearing. This innovative blood-lubricated fluid film bearing allows the rotating assembly to revolve levitated on a cradle of blood, eliminating any surface contact between moving parts. The blood-contacting materials used within the blood pump include titanium 6Al4V, polytetrafluoroethylene, polyimide, and amorphous carbon plating.
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Fig 1. (A) Three major components of the CorAide blood pump assembly. (B) CorAide blood pump cross section.
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The nominal design point for the CorAide blood pump is 5 L/min and a 100–mm Hg pressure rise, matched to a pump speed of 2850 rpm, at a power consumption less than 6.0 W. The blood shear stress in the fluid film is minimized such that there has been no evidence of hemolysis during in vivo testing. This pump demonstrates a comforting tolerance to mechanical shock while being subjected to intentional impact loading, such as hammer blows and slamming onto a tabletop during operation on the bench.
Physiologic control algorithm
To provide automatic pump control without intervention of medical personnel, the CorAide physiologic control algorithm has been developed [12]. A "sensorless" physiologic monitoring system does not require implanted flow, electrocardiogram (ECG), or pressure sensors. A microprocessor-based physiologic controller acquires only pump power and speed data over a 10-second control interval, from which the heart rate (HR), pump flow characteristics (mean, maximum, minimum, and pulsatility index) and systemic arterial pressure (AoPcalc) are derived. Heart rate is determined by analyzing the motor current waveform, assuming that the HR defines the fundamental frequency of the waveform. Pump motor power and speed waveforms are used to calculate instantaneous pump flow. After calculating the pump flow, the peak pump inlet–outlet conduit pressure difference (AoPcalc) is derived from the pump normalized pressure–flow curve. In this algorithm, the controller adjusts pump power to maintain a targeted pump flow that is a function of the HR to AoPcalc ratio (HR/AoPcalc). This flow response can be optimized to match patient size and physiologic conditions. Due to residual ventricular function, the CorAide pump flow remains pulsatile even though it is a continuous-flow device (Fig 2). To maintain safe operation, programmed limiting conditions include minimum and maximum allowable pump speed and flow, minimum and maximum afterload and HR response, and minimum allowable pump flow pulsatility. Pump power is adjusted to prevent suction of the left ventricle by monitoring the calculated flow pulsatility.
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Fig 2. Hemodynamic traces during CorAide support. (AoP = measured arterial pressure; Pump Flow = measured pump flow; Pump Power = electrical power to the pump motor driver.)
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In vivo experiments
Surgical procedure
From June 1999 through August 2000, chronic CorAide blood pump implantation was performed in 13 calves (weight 80 to 105 kg, mean 88 kg). All animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" prepared by the Institute of Laboratory Animal Resources, National Research Council, and published by the National Academy Press (revised 1996).
Animals were anesthetized with inhalational halothane, ventilated through an endotracheal tube, and monitored continuously for arterial blood pressure and ECG. The CorAide blood pump was implanted through a left thoracotomy. An outflow graft (14 mm in 10 cases and 12 mm in 3 cases; Cooley, low-porosity, woven polyester graft, Meadox Medicals, Oakland, NJ) was preclotted with nonheparinized autologous blood. The distal end was anastomosed to the aorta in an end-to-side manner reinforced with Teflon felt. The blood pump surfaces were preconditioned with an albumin/heparin solution. After opening the pericardium, 100 mg of lidocaine was injected to avoid ventricular arrhythmias during manipulation of the heart. Two pursestring sutures with pledgets were placed on the left ventricular (LV) apex. After heparinization (2 mg/kg), the clamped outflow graft was connected to the pump outflow port. An ultrasonic perivascular flow probe (Transonic Systems Inc, Ithaca, NY) was placed around the outflow graft for continuous monitoring of the pump output. The LV apex was clamped with a side clamp and then incised to insert the inflow cannula into the LV after the removal of the clamp. The inflow cannula (12-mm internal diameter) was connected to the pump, and air was evacuated through a needle in the outflow graft. Pumping was started as the clamp on the outflow graft was removed. The pump was positioned in the left chest, and the flow probe cable, pump motor cable, and arterial pressure monitoring line were exteriorized.
Physiologic monitoring and postoperative care
After completion of surgery, all animals were transferred to a chronic care facility for physiologic monitoring. The calves were kept in cages throughout the duration of these studies. No exercise studies or additional manipulation of hemodynamic preload or afterload were used to evaluate pump physiologic control. Heparin was adjusted to maintain activated clotting time (ACT) values at approximately 1.2 times baseline in the first 12 cases. In case 13, heparin was discontinued on postoperative day (POD) 7, after which no further anticoagulants or antiplatelet therapy was used. Intravenous nitroprusside was administered to maintain mean arterial pressure (AoP) at less than 125 mm Hg and pump flows greater than 3.5 L/min. Serial blood samples were collected to determine blood cell counts, blood chemistry values, and levels of plasma free hemoglobin.
An Astro-Med MT95K2, 16-channel data acquisition and recording system (Astro-Med, Inc, West Warwick, RI) continuously recorded AoP, ECG, pump flow, pump motor current, and pump speed waveforms. Mean values for AoP, pump flow, current, and speed were recorded hourly, along with thermal recorder waveform traces.
Autopsy
At the completion of each study, a thorough autopsy was performed, focusing on postexplant device evaluation, detection of infection, and systemic organ pathology. Macroscopic examination for thromboembolism and gross organ pathophysiology included the following: (1) opening all major branches of the systemic arterial tree to the common iliac artery; (2) gross examination followed by 1.5-cm sectioning of the lungs, kidneys, liver, spleen, adrenals, and pancreas; and (3) gross examination of the digestive tract through its length for signs of hemorrhage or discoloration. Any organ pathology or device deposition noted was investigated further by histologic evaluation.
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Results
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Experiment duration and outcome
The first 9 cases were studied for approximately 1 month to finalize the blood pump design, and the next 3 cases for 3 months as in vivo pump performance validation studies. The 13th study was conducted for 1 month to evaluate the biological effects of running the CorAide blood pump without the use of anticoagulants. A total of 1.5 years of cardiac support was accumulated over a 14-month period. Eleven cases were electively terminated at the completion of their scheduled duration. Two studies were terminated nonelectively, one at POD 39 (case 5) because of a cable connector failure and one at POD 29 (case 6) because of blood-bearing complications resulting from a manufacturing surface defect in the rotating assembly seam. There was no incidence of blood pump component mechanical wear or structural failure, bleeding, hemolysis, or systemic organ dysfunction in any of the 13 cases.
Hemodynamics and pump performance
A summary of hemodynamic and pump performance measurements is given in Table 1. Data are expressed as mean ± SD. As shown in Figure 2, pump flow was pulsatile during each cardiac cycle. The recorded mean maximum and mean minimum flows during each cardiac cycle for all cases were 9.6 ± 1.9 and 2.9 ± 0.8 L/min, respectively. The mean pump flow (6.1 ± 1.1 L/min), AoP (97 ± 5 mm Hg), pump speed (2828 ± 121 rpm), and power consumption (6.8 ± 1.0 W) for all cases were consistent with in vitro hydraulic performance data.
Demonstration of physiologic control
Cases 11 and 12 accumulated more than 35 days of operation under the CorAide physiologic control algorithm without any hemodynamic complication. Pump flows of 4.5 to 7.5 L/min were recorded over a programmed allowable speed range of 2,650 to 2,900 rpm in response to heart rates of 63 to 117 beats per minute and mean AoP values of 82 to 122 mm Hg. Figure 3 demonstrates a pump flow response from 5.7 to 7.0 L/min for a range of HR/AoPcalc ratios of 0.82 to 1.17. These data track the preprogrammed target flow versus HR/AoPcalc relationship.
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Fig 3. CorAide physiologic control flow response to a range of heart rate (HR) to estimated systemic arterial pressure (AoPcalc) physiologic ratios from case 12. Data were obtained after each successive 10-second physiologic control interval of more than 3 hours’ duration. The heavy line was the preprogrammed targeted response for this study. HR and AoPcalc are calculated based on pump motor power and speed inputs. Pump flow was a measured value.
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Biologic response
The hemoglobin levels dropped from baseline (12.1 ± 1.0 g/dL) in the first week and then stabilized at 8.9 ± 1.0 g/dL. After POD 3, plasma free-hemoglobin levels averaged 2.0 ± 1.8 mg/dL, which confirmed low hemolysis (Fig 4). Indices of renal and liver function such as creatinine (0.3 to 1.2 mg/dL), blood urea nitrogen (BUN; 3 to 24 mg/dL), and total bilirubin (0.1 to 0.9 mg/dL) remained within laboratory normal ranges, whereas aspartate aminotransferase (AST) values returned to baseline on POD 14. Total protein (6.1 ± 0.3 g/dL) and albumin (3.3 ± 0.2 g/dL) also recovered to near baseline on POD 14. The ACT values were 1.21 ± 0.06 times the preoperative baseline values for all cases except case 13.
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Fig 4. Mean hemoglobin and plasma free-hemoglobin values for all cases. (POD = postoperative day; Pre = preoperative level.) The mean values of Pre, POD 1, POD 7, POD 14, POD 21, and POD 28 are derived from all 13 cases. The mean values of POD 60 and POD 90 are derived from 3 cases of 3-month studies.
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Autopsy results after an accumulated 589 implant days revealed one incident of device infection and two indications of emboli to a systemic organ. Case 11 showed one small macroscopic renal infarction associated with resolving bacterial infection and diffuse thrombus throughout the length of the pump outflow graft. Case 7 also showed a single microscopic renal cortical infarct. In 8 cases (cases 2, 4, 6 to 9, 12, and 13), a cellular fibrous tissue growth frequently terminating with thrombus was noted at the LV apex adjacent to the outer diameter of the inflow cannula. This tissue growth was found to be due to invagination of apical myocardial tissues into the LV apex during rapid insertion of the inflow cannula, and was minimized in later cases by increasing the diameter of the cored LV during insertion. Thrombus was noted at the blood pump stator housing fluid film bearing surface in cases 1, 2, and 3. These initial cases were used to evaluate successive design changes to critical CorAide blood pump components. After optimizing the stator surface geometry empirically and using preimplantation albumin/heparin pump priming, there was no incidence of deposition adhering to the fluid film bearing surface in the last 10 cases (489 implant days). Only 1 of the 10 remaining cases showed deposition inside the blood pump. The thrombus at the rotating assembly secondary impeller in case 6 was eliminated in the remaining 7 cases (393 implant days) after a redesign of the secondary impeller blade geometry and a modification in the rotating assembly manufacturing procedures. It was notable that no thromboembolism or blood pump deposition was found at autopsy of case 13, conducted without anticoagulants or antiplatelet therapy after POD 7.
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Comment
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The cumulative 1.5 years of animal in vivo testing has shown that the CorAide pump design is easily implanted and provides good blood flow at low power levels. It is demonstrated to be reliable, nonhemolytic, and nonthrombogenic with minimal anticoagulation therapy. Integration of pump function with residual cardiac function was achieved by the CorAide automatic control algorithm, responding appropriately to physiologic perturbations.
Implantable blood pumps have recently been classified based on their historic development and their pumping mechanism. First-generation blood pumps are pulsatile in nature and simulate the LV, eg, HeartMate 1000 IP and VE (Thoratec Laboratories Corp, Pleasanton, CA), Novacor LVAS (World Heart Corp, Ottawa, ON, Canada), and Thoratec VAD (Thoratec Laboratories Corp, Pleasanton, CA) [13, 14]. Second-generation pumps are continuous-flow rotary devices characterized by a rotating assembly supported by mechanical pivot bearings [15–17]. The major advantages of these devices over first-generation pumps are their small size, absence of valves, elimination of the compliance chamber or external vent tube, lower power consumption, and lower cost. The pivot bearings, however, pose potential risks of wear, deposition and being subject to shock and handling damage. Third-generation pumps such as CorAide are continuous-flow rotary pumps in which the rotating assembly is fully suspended and noncontacting [18–20].
The success of current first-generation clinical LVAS programs as a bridge to cardiac transplantation and the shortage of available donor hearts have directed the worldwide medical community and the European and United States regulatory agencies to address the device requirements for permanent LVAS support as a treatment for end-stage heart failure. This has been termed destination therapy [7]. A minimum 5-year mission life, no life-limiting wear, high reliability, shock tolerance, low cost, and nonthrombogenic blood-contacting surfaces were the requirements established by the CorAide design team for permanent LVAS support. Problematic components such as pivot bearings, position sensors, electromagnets, and extra position control electronics were absolutely avoided in design.
The combination of hydrodynamic support of the rotating assembly in the radial direction and passive magnetic positioning in the axial direction resulted in operation of the CorAide pump with no surface contact and no mechanical wear. The design goal of no contact, no wear, and no thrombus has been achieved with this simple innovative pump design, positioning it as a leading third-generation, continuous-flow LVAS, with a completely suspended rotor.
Future goals
A series of in vivo studies in calves is underway to validate safe use of the CorAide pump without the use of anticoagulants. A clinical percutaneous CorAide system currently under development is illustrated in Figure 5. The small (15.2 x 8.7 x 2.5 cm), belt-mounted, portable electronic module contains the integrated motor and physiologic controllers and will be evaluated in future in vivo validation studies in calves. The Cleveland Clinic Foundation has initiated contacts with commercial companies to transfer the CorAide blood pump technology to industry for worldwide distribution and clinical use.
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Fig 5. The Cleveland Clinic CorAide percutaneous left ventricular assist system configuration. The pump is placed in the left thoracic cavity. The left ventricular apex is cored for insertion of the inflow cannula and a prosthetic vascular graft is anastomosed to the ascending aorta for the pump outflow. A percutaneous pump cable transmits power to the motor from the portable electronics module. System power input to the portable electronics module is by means of two portable external batteries.
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Acknowledgments
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We thank Michael Kopcak for technical assistance, and C. R. Bard, Inc, Cardiosurgery Division, Billerica, MA, for donation of fabrics used in this project. This study was supported in part by contract N01-HV-58155, issued by the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
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Abstract
Introduction
