The Jarvik 2000 Oxford system: increasing the scope of mechanical circulatory support.

METHODS: We developed a system for mechanical circulatory support based on the Jarvik 2000 intraventricular axial flow impeller pump (Jarvik Research, Inc., New York, N.Y.) and percutaneous electric power. The adult pump provides flow at a rate up to 10 L/min with an energy requirement of 7 to 10 watts. The device was implanted into the apex of the left ventricle through a left thoracotomy without cardiopulmonary bypass. A Dacron graft conveyed blood to the descending thoracic aorta. In patients, we will use a skull-mounted carbon pedestal to transmit fine electric wires through the scalp skin. Being highly vascular, the scalp skin is resistant to infection. RESULTS: We tested 16 adult systems and one pediatric system in 17 adult ewes weighing between 60 and 90 kg. Five died of perioperative complications. Twelve survived between 3 and 198 days (mean 44 days) with a functioning device. None of the sheep could receive adequate anticoagulation with warfarin (INR 1.0 to 1.5). Acute thrombotic occlusion occurred after a 3-hour power loss in one device (46 days) but was cleared with streptokinase. In a second animal with endocarditis, the pump inflow became occluded with vegetations. No other device-related problems or important hemolysis developed despite pump speeds between 10,000 and 18,000 rpm. Renal function remained normal in all animals. Autopsy studies showed no pannus ingrowth at the device inflow despite the restrictive left ventricular cavity size. No sign of thromboembolism could be detected in the brains or kidneys. CONCLUSION: Our findings indicate the Jarvik 2000 Oxford System to be a safe and effective circulatory assist device. Potential uses include permanent circulatory support, bridge to transplantation, or bridge to myocardial recovery in acute or chronic left ventricular failure.

Miniature axial flow pump for ventricular assistance in children and small adults.

We investigated the efficacy of the Jarvik 2000 intraventricular assist device (Jarvik Research, Inc., New York, N.Y.) in an ovine model. The device is an axial flow pump measuring 1.8 cm in diameter by 5 cm long, has a displacement volume of 12 ml, and can deliver flow from 2 to 7 L/min. Seven devices were implanted through a left thoracotomy into the left ventricle with an outflow graft to the descending aorta. Animals were treated with warfarin sodium and aspirin to maintain prothrombin times approximately 1.5 times control. Animals were followed up for 3 to 123 days. Two animals died of operative complications at days 3 and 5. One device failed at 58 days because of thrombus formation at the inflow side of the impeller. The remaining four animals were killed at days 19, 42, 42, and 123, respectively, because of broken electric power cables. Hematocrit values rose significantly higher than preoperative levels (22.8% +/- 3.8% to 30.5% +/- 3.4%); premortem elevations of values higher than baseline values of plasma free hemoglobin (10.4 +/- 7.8 mg/dl to 17.1 +/- 7.4 mg/dl) and lactate dehydrogenase (391.5 +/- 113.7 units/L to 771.2 +/- 370.8 units/L) were statistically insignificant. Serum creatinine and bilirubin levels were normal. No end-organ dysfunction arising from long-term support was evident clinically or at postmortem examination, nor was there any evidence of embolism or damage to intracardiac structures. We found the Jarvik 2000 intraventricular assist device to be easily implantable, safe, nonhemolytic, and able to provide physiologic flow with power requirements under 10 watts.

Six-month survival of a calf with an artificial heart.

A pneumatically powered artificial heart, constructed primarily from a polyurethane, was implanted in the chest of a calf and supported the calf for more than 6 months. The heart, which was designed to fit in the chest of a 90 kilogram calf, was able to suppor the animal when it weighed 180 kilograms. During the first 105 days the calf remained strong and healthy. The animal grew progressively weaker after day 106, and by day 160 right heart failure became apparent. The principal cause of the right heart failure was an obstructive growth between the right atrium and the right ventricle. An attempt to correct the problem on day 184 with an artificial heart resulted in the animal's death.

Survival for 18 days with a Jarvik-type artificial heart.

This is a report of an experiment wherein a calf had its natural heart replaced with an artificial heart and survived for 18 days and 20 hours. All measured physiologic parameters remained normal until the fourteenth day. Thereafter a gradual persistent rise in venous pressure and signs of a decreased cardiac output occurred. However, the animal outwardly appeared normal until the eighteenth day. During the nineteenth day it became comatose and was killed. At autopsy large thrombi were found in both atria, impairing ventricular filling, resulting in venous congestion and diminished cardiac output. This extended survival time and our ability to understand and eliminate the problems associated with artificial heart implantation give support to our hope that artificial hearts for man will be possible in the not too distant future.

LVAD power delivery: a percutaneous approach to avoid infection.

BACKGROUND: Driveline infection limits the event-free survival of patients with a left ventricular assist device. With the evolving prospect of improved left ventricular assist devices in the bridge-to-transplantation or recovery setting, we sought to reduce the risk of driveline complications. METHODS: As part of the Oxford Jarvik 2000 research program, we developed a carbon and then titanium pedestal to transmit the electric wires through the skin. In a sheep model, the pedestal was brought out through the skin of the shoulder (n = 10) or the scalp (n = 9) with underlying fixation to the skull. Exit wounds were carefully inspected for healing and infection. Power cable durability tests were performed in 6 additional animals without an implanted pump. RESULTS: The cumulative observation period was 1,491 days (mean time, 78 days; range, 14 days to 198 days). There was no difference in observation period between the two groups. Infection (n = 2) and impaired healing (n = 5) occurred in the mobile tissues at the shoulder. Skull-mounted pedestals were free from infection or healing problems. The electric cables were not interrupted by repeated neck flexion (cumulative observation period, 588 days). The carbon pedestal was replaced by a titanium pedestal when the head butting of the sheep fractured the carbon. CONCLUSIONS: The combination of rigid fixation and highly vascular scalp skin reduces the risk of percutaneous driveline infection and may solve an important outstanding problem in use of left ventricular assist devices.

Development of an implantable ventricular assist system.

BACKGROUND: This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system. METHODS: Designed for implantation in the human thorax, the system consists of a small (25 cm3, 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-flow impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage. RESULTS: Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device. CONCLUSIONS: These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients.

Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart.

Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

Durability testing of components for the Jarvik 2000 completely implantable axial flow left ventricular assist device.

A cable-lead tester and real time bearing tester have been developed with provisions to test future implantable electronics, transcutaneous energy transfer system (TETS), and related interconnect cabling designs. The cable/lead tester, used in 1997 to test a previously considered implantable bellows-connector-cabling system, can test up to 10 samples at a time. X-Y-Z-theta motions are applied to the proximal end of the test specimen with its distal end fixed. The real time bearing tester is of a mock loop configuration with the bearings under test housed in a fully functional, Good Manufacturing Practices assembled axial pump. A simulated left ventricular pulsatile preload is applied to the inflow of the axial pump, while its outflow is subjected to an 80 mmHg aortic afterload by pumping into a fixed height tube with no outflow restriction. The heated blood bath saline used in this system is UV sterilized and mechanically filtered by use of a commercial salt water conditioning system attached external to the main preload fluid reservoir. The cable-lead tester and real time bearing tester design include provisions to house a complete Jarvik 2000 left ventricular assist device (Transicoil Medical, Norristown, PA) for in vitro system testing.

In vivo evaluation of an intraventricular electric axial flow pump for left ventricular assistance.

In vivo studies have begun to evaluate a new intraventricular electric axial flow left ventricular assist device (LVAD), the Jarvik 2000, which is a small, valveless pump that is placed inside the left ventricle through the left ventricular apex. The operation, which is performed through a left thoracotomy, may be done without cardiopulmonary bypass and aortic cross-clamping. Outflow is provided through a 16 mm softly woven, Dacron graft anastomosed to the descending thoracic or abdominal aorta. Pump flow, which varies from 2 to 16 l/min in vitro, is changed by adjusting the speed of pump rotation. Preliminary studies were done to evaluate the ease of implantation, hematologic and anatomic compatibility, and pump performance. The device has been implanted in seven healthy, preconditioned calves (83-138 kg), one of which is currently undergoing support. The implantation procedure averaged 3 hours. There were no operative deaths, and blood transfusions were not required. Postoperatively, anticoagulation was achieved with heparin followed by warfarin sodium to maintain prothrombin time or partial thromboplastin time at 1.5-2.0 times baseline. In the six completed studies, support time ranged from 2 to 120 days (mean, 36 days). The seventh calf has been supported for 30 days. In the four long-term studies (20, 70, 120, > 30 days), the mean plasma free hemoglobin values during support were 11.0, 7.7, 6.6, and 3.4 mg/dl, respectively. Under normal conditions, the average daily flow rate ranged from 5 to 6 l/min. During treadmill exercise (10% grade, 1.5 km/h) lasting 20 minutes, peak flow rates exceeded 8 l/min. These pilot studies suggest that this intraventricular axial flow pump is relatively easy to implant, operate, and control. In addition, it is hemocompatible, provides physiologic flow rates, and may be able to provide long-term circulatory support.

Mechanical unloading with a miniature in-line axial flow pump as an alternative to cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) causes a well described systemic inflammatory response. To avoid these potential detrimental effects, coronary artery bypass grafting (CABG) has been attempted off CPB on the beating heart. With the use of a left ventricular (LV) assist device during CABG, the heart can be made flaccid with beta-blockade, and the systemic circulation can continue to be supported. The hemodynamic and hematologic consequences of left heart bypass with a miniature axial flow pump were studied in a sheep CABG model. The pump weighs 45 g and was connected to standard venous and arterial cannulas. Left sided inflow and brachiocephalic outflow were employed. A pump speed of 14,000 rpm resulted in a flow of 5.63 +/- 0.18 L/min and provided 75% of the LV output during a 2 hr pump run. This resulted in complete capture of the aortic pressure tracing (mean 56.3 mmHg) with a 15.5 mmHg augmentation in the esmolol depressed ventricle. Reductions in LV end diastolic pressure and LV end systolic pressure resulted in a 66% reduction in LV external work under baseline conditions and an 83% reduction in the beta-blocked ventricle. Myocardial oxygen demand was reduced 16% after axial flow unloading in the esmolol depressed condition. Right ventricular pressures, pulmonary artery flow, LV filling, and oxygenation were adequate in the esmolol depressed animal and remained unchanged throughout the experiment. No changes in hematocrit, total bilirubin, lactate dehydrogenase, or plasma free hemoglobin were detected after 2 hr of assist. Axial flow left heart bypass results in acceptable hemodynamics with no hemolysis and may provide an alternative to CPB during CABG.

Five month survival in a calf supported with an intraventricular axial flow blood pump.

We are studying in vivo an intraventricular axial flow blood pump (Jarvik 2000) designed for long-term left ventricular support. The small (25 cc, 85 g) valveless pump has been placed intraventricularly in seven calves; pumps have functioned for as long as 5 months. In the four most recent long-term studies completed, calves have survived for 70, 120, 155, and 162 days (in that order); weight gain has averaged 0.56 kg/day. One study is ongoing at more than 30 days. Under resting physiologic conditions in the normal calf, the continuous flow pump produces flows of 5-6 L/min with a decreased arterial pulse contour. The device has caused no physiologic complications. Calves in the completed studies had mean free plasma hemoglobin levels of 11.4, 7.1, 6.5, and 4.3 mg/dl, respectively. We have modified the inflow structures of the device, and these results suggest that a thrombus free design with no pannus at or around the inlet of the pump can be achieved. Histopathologic analyses of the heart and kidneys in studies of as long as 5 months show no deleterious effects of this device. These studies demonstrate the feasibility of a small implanted intraventricular blood pump for long-term use. Future developments for permanent implantation will include implanted physiologic control systems, transcutaneous energy transmission systems, and implanted batteries.

Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system.

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 +/- 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (approximately 1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

The beat goes on: status of the artificial heart, 1977.

After two decades of continuous research on the artificial heart, survival times of experimental animals indicate that clinical application of such a device is definitely feasible. However, a number of problems remain to be solved. Durability of the device, infection, pannus formation at the interface between the device and natural tissue and thrombosis within the device appear to be the major problems. Development of an implantable power source is also an area of important research. Questions of efficiency, cosmetic and psychological acceptability and cost are just beginning to be considered.

System considerations favoring rotary artificial hearts with blood-immersed bearings.

Hydrodynamic blood pumps provide such advantages as not requiring an air vent or compliance chamber as well as a great reduction in mechanical complexity with the potential for very long durability. The detailed design of their bearings is emerging as the single most important determinant of long-term success. Three categories of bearings include remote force, such as magnetic suspension; blood-isolated, which require a shaft seal; and blood-immersed using either mechanical or hydrodynamic support. Blood-immersed bearings permit maximum simplification and miniaturization of the entire system, require no flush fluid, and require no electronics as with magnetic suspension. The Jarvik 2000 heart represents an example of their potential. The intraventricular titanium pump (25 mm diameter, 25 cc, 85 g), uses blood flow through the motor air gap with blood-immersed bearings. The longest in vitro bearing durability test is ongoing at 20,000,000,000 revolutions with minimal wear (3 years at 15,000 rpm). In vivo results include 5-month calf survival, no thromboembolism, plasma Hb 2-5 mg%, and power under 10 W.

Electrical energy converters for practical human total artificial hearts--an opinion in support of electropneumatic systems.

Until recently, most artificial hearts have served as research tools to acquire further knowledge necessary ultimately to design practical systems for human use. Transcutaneous systems or percutaneous systems utilizing permanently implanted energy converters, batteries, and electronics packages have a number of substantial problems that would not exist if most system elements were kept outside the body. These problems include physiologic control, fit and fixation, foreign body infection, hermetic sealing, cable insulation and fatigue, inherent system complexity, stringent requirements for maintenance-free operation with long-term high reliability, and high cost. Percutaneous systems, particularly those in which only the blood pump is implanted, are an attractive choice for practical systems in the near future. A wearable, battery-powered electropneumatic total heart system should be developed.

Belt worn control system and battery for the percutaneous model of the Jarvik 2000 heart.

A belt worn controller and lithium-ion battery pack have been developed for use with the initial clinical trials of the Jarvik 2000 heart. Patient interface considerations, safety, and simplicity were major design inputs for the system. The controller was developed using all analog technology to avoid difficulties with electromagnetic interference (EMI), to minimize susceptibility to electrostatic discharge, and to avoid the need for software validation. Manual control of pump speed is accomplished by a patient operated knob, according to physician instructions for rest and exercise for each individual patient. The system includes alarms and indicators which show the following: the amount of remaining battery charge, if the battery is low and needs replacement, the power in watts being consumed, if the power consumed is above 15 W, if the pump is running below the selected speed setting, and if the pump stops. The control box, curved to be worn on the belt, is only 2.5 inches high for comfort when sitting. The battery pack, also form fitted for patient comfort, weighs just over 1 1/2 pounds and supplies 65 W-h of energy storage, sufficient to run the device for over 8 h at nominal load.

Response of the human body to the first permanent implant of the Jarvik-7 Total Artificial Heart.

The success of the first permanent total artificial heart implant would have been more obvious had the patient been able to be transferred from the hospital to an outlying home care setting. Nevertheless, several major achievements were realized. First, we were able to demonstrate that the total artificial heart will fit within an adult male chest without causing obstruction to inflow or outflow channels. Second, we were able to demonstrate that the total artificial heart would sustain life on a long-term basis (at least up to 112 days) without any evidence of systemic or local infection and without any untoward systemic effects. Third, we were able to demonstrate that the patient was able to tolerate a total artificial heart without complaint of the noise or the bulk of the drive system to which he required permanent attachment and that the patient could be comfortable and totally free of pain. An additional finding, which could not be assessed in the animal experimentations, was the fact that the patient was able to maintain higher CNS activity on an undisturbed basis following the implant of the total artificial heart. It is for these reasons that the entire University of Utah Medical Center staff feel great indebtedness to the patient and his family for demonstrating to the world the feasibility and the necessity for pursuing this device as a new therapy for end-stage heart disease.

Jarvik 2000 heart: potential for bridge to myocyte recovery.

BACKGROUND: Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose. METHODS AND RESULTS: The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft. CONCLUSIONS: The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.