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The Artificial Heart: Prototypes, Policies, and Patients (1991)

Chapter: Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems

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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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C

Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems

GERSON ROSENBERG

THE CONCEPT OF MECHANICAL CIRCULATORY SUPPORT was first postulated by LeGallois in 1812 (LeGallois, 1813). Much later, in 1934, DeBakey proposed a simple continuous flow blood transfusion instrument that was a simple roller pump (DeBakey, 1934). In 1961, Dennis and colleagues performed left heart bypass by inserting cannulae into the left atrium and returning blood through the femoral artery (Dennis, 1979). In 1961, Kolff and Moulopoulos developed the first intra-aortic balloon pump (Moulopoulos et al., 1962). In 1963, Liota performed the first clinical implantation of a pulsatile left ventricular assist device (Liota et al., 1963). In 1969, the first implant of a total artificial heart was performed by Denton Cooley (Cooley et al., 1969). Mechanical circulatory support has been used in over 1,300 patients since 1985. There have been implants of approximately 186 total artificial hearts, 600 left ventricular assist devices, and 112 right ventricular assist devices along with 409 biventricular assist devices. Of these 1,300 patients, over 600 have been weaned and approximately 365 have been discharged from the hospital (Joyce et al., 1988; Pae and Miller, 1990).

Progress in the use of ventricular assist devices and artificial hearts has been excellent. In the 1970s, animal survival with the total artificial heart

Gerson Rosenberg is Research Professor and Assistant Chief, Division of Artificial Organs, Department of Surgery, Milton S. Hershey Medical Center, Hershey, Pennsylvania, and Professor of Bioengineering, College of Engineering, The Pennsylvania State University, University Park, Pennsylvania. This appendix is based on a paper submitted to the Institute of Medicine committee in October 1990 and thus reflects developments and the literature as of that date.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

was averaging approximately two weeks; animal survivals today are approaching one year, and patients have survived for almost 600 days with artificial hearts. The use of temporary ventricular assist devices is becoming more routine, and the development of permanent left ventricular assist devices and total artificial hearts is well under way. Yet with all the progress that has been made, there are currently several complications associated with the permanent application of left ventricular assist devices and total artificial hearts. These can be broken down into durability and biocompatibility (including bleeding, thrombosis, sepsis, calcification, and hemolysis). These factors appear in various degrees in all of the devices and will be discussed, but they do not appear to be insurmountable problems; in fact, several appear to be close to solution.

CURRENT STATE OF THE TECHNOLOGY IN MECHANICAL CIRCULATORY SUPPORT SYSTEMS

Artificial hearts and circulatory assist devices are currently under development in the United States, Korea, Russia, Canada, Switzerland, Japan, Germany, Czechoslovakia, Italy, France, Australia, China, and other countries. A detailed description of all of these devices is beyond the scope of this document, and only those with significant design features or devices sufficiently developed to be nearing clinical trials will be discussed.

The most frequent clinically used mechanical circulatory support systems (MCSSs) are those currently manufactured in the United States (Pae and Miller, 1990). The animal survival times with pneumatically powered devices are essentially the same in the United States and abroad, indicating approximately the same technology level (Total Artificial Heart, 1985; Total Artificial Heart, 1987). Electric motor-driven circulatory assist and artificial heart devices are, at the present time, more advanced in the United States than in any other country, although devices in Japan (Total Artificial Heart, 1985) and Switzerland (Odermatt, 1989) are advancing rapidly.

All of these MCSSs have met with similar difficulties in development and application. These difficulties include device durability and biocompatibility. Various solutions have been implemented for these problems and have allowed devices to function for over a year in vivo and greater than two years in vitro.

Short-Term-Use Devices (fewer than 180 days)

Both total artificial hearts and univentricular or biventricular assist devices can be utilized temporarily for mechanical circulatory support. All of the total artificial hearts that have been utilized clinically have been pneumatically powered devices. The ventricular assist devices that have been

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

utilized clinically include pneumatically or electrically powered pulsatile devices and nonpulsatile devices.

Total Artificial Heart

For the purposes of discussion, total artificial hearts will be considered those devices that are orthotopically placed with the removal of the native heart, thus distinguishing these devices from biventricular assist devices.

Animal and Clinical Results

Over the past decade, several short-term pneumatic artificial hearts have received significant development. These devices include the pneumatic artificial hearts of The Pennsylvania State University (Penn State) and the Free University of Berlin, the Jarvik or Symbion artificial heart originally developed at the University of Utah, the Cleveland Clinic Foundation heart, and the heart of the University of Perkinje in Bruno, Czechoslovakia. Other hearts are being developed in Tokyo, Japan (Pierce, 1986; Total Artificial Heart, 1989). The longest survival with a pneumatic artificial heart in a calf or sheep is 353 days, accomplished by the Penn State group (Aufiero et al., 1987). A sheep at the University of Utah lived for 297 days and a goat with a pneumatic artificial heart lived for 344 days at the University of Tokyo. The Tokyo heart was not orthotopically placed, but was located outside the animal's thoracic cavity. Thus, it is accurate to say that a small percentage of the artificial heart animals have been able to survive for slightly less than one year. Several factors contribute to this one-year time limit. In the growing animal such as the calf, the animals have the potential to outgrow their cardiac output. Typically, pneumatic artificial hearts are capable of pumping a maximum of 12 liters per minute. Normal healthy calves will gain as much as 1 kilogram per day. Starting with a 100-kilogram animal gaining just 1 kilogram a day, the calf will outgrow the heart in less than one year based upon a minimum cardiac output of 70 milliliters per minute per kilogram. Calcification has also been a problem in the growing animal, causing device failure through rupture of the polymeric sac. Sepsis and, to some degree, thrombosis have been present in the long-term animals.

The experience at Penn State for 21 consecutive pneumatic artificial heart animals indicates that 3 died from pannus formation, a proliferation of unwanted tissue in the inlet of the artificial hearts. (This problem has been remedied and has not occurred for four years.) Of the 21 animals, only 1 died from a thromboembolic event. Technical error caused five of the animals to die. One animal died of anticoagulant-related bleeding, and two of the longest-surviving animals, living 275 and 353 days, respec-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

tively, died of cardiac cachexia. These animals basically outgrew their artificial hearts. Mechanical failures were responsible for 9 of the 21 animal deaths (43 percent). Blood sac or diaphragm perforations occurred in six of the nine animals that died as a result of mechanical failure, which was related to stress and/or calcification of the flexing polymer. Since Penn State instituted medical therapy with warfarin sodium and etidronate disodium to retard calcification, along with design changes to reduce the stress experienced with the flexing surfaces, there has not been any failure from these causes in pneumatically driven pumps. Although not a cause of death, sepsis was present in many of these animals (Pae et al., 1987). It should be noted that valve failure and drive system failure have not been a cause of death in these animals.

Clinical results with pneumatic short-term artificial hearts are limited almost exclusively to the results with the Jarvik 100-cubic centimeter (cc) and 70-cc stroke volume devices and may not be indicative of other devices. As of 1990, there have been 186 applications of pneumatic total artificial hearts; 127 of those patients were weaned, and 62 were transplanted and discharged. As previously stated, the largest percentage of those patients received the Jarvik/Symbion-type artificial heart. Of the 186 patients to receive pneumatic total artificial hearts, the major complication was bleeding and reoperation in 28 percent of the patients. Renal failure occurred in 19 percent of the patients. Hemolysis occurred in 7 percent of the patients, respiratory failure occurred in 13 percent, thrombosis in the system occurred in 4 percent, and embolus occurred in 9 percent, for a total of 13 percent for thromboembolic complications. Infection occurred in 21 percent of the patients (Pae and Miller, 1990).

Technological Development of Pneumatic Total Artificial Hearts

Durability. Pneumatic artificial hearts have functioned in animals for approximately one year, and there have been devices that have functioned on the mock circulatory system, at various institutions, for periods in excess of two years. Insufficient studies have been done to accurately predict the reliability of these devices. The clinical registry data indicate that mechanical failure was present in 1 percent of the patients who received the total artificial heart. Similar sac-type blood pumps utilized for left ventricular assist devices have demonstrated a two year reliability in vitro (Jaszawalla et al., 1988). Thus, the durability for short-term application of total artificial hearts appears to be quite adequate, with approximately 1 percent mechanical failures in 186 clinical applications. It is interesting to note that the device that received the most widespread clinical use, the Symbion device, was withdrawn from the market by the Food and Drug Administration. The Food and Drug Administration discontinued the

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

device's trials owing to the inadequacy of the methods, facilities, and controls used for the manufacturing, processing, and installation of the device and the inadequacy of the monitoring and review of the investigation. The investigational device exemption (IDE) was also withdrawn because Symbion did not provide assurance that the integrity of the device had been maintained by adhering to the original design specifications and manufacturing controls and that the clinical studies being performed were adhering to the clinical protocols approved in the original IDE. Thus, the device was withdrawn not because of poor performance but rather because of inadequate manufacturing and application of the device.

Control. Throughout the development of the artificial heart, there have been various control schemes proposed for the artificial heart. The majority of artificial hearts are controlled in a Starling-like manner or fill-limited mode. Thus the device will pump blood that is returned to it within a particular range of cardiac outputs. One of the problems with this type of control system is that the gain is somewhat limited. Thus, it requires large changes in filling pressure to effect physiologic changes in cardiac output. The Penn State group has utilized an electronic automatic control system to control the devices for not only cardiac output but also actively balancing the left and right pumps. This cardiac output control system is sensitive to pump afterload, and balancing is accomplished by indirect sensing of left atrial pressure (Snyder et al., 1986). Other systems have been proposed and tested, such as systems measuring the P-wave from the remnant atrium or using various ChemFETS or other devices to measure blood chemistry values. It does not appear that animal survival has been limited by the various control schemes, since the major groups differ in control method but have essentially the same survival times. Various control schemes may require continuous monitoring and adjustment to maintain balance or cardiac output, while others perform this task automatically. It appears that as long as the control system can maintain a physiologic left atrial pressure, provide a resting cardiac output in the range of 70 milliliters per minute per kilogram, and allow for changes in cardiac output as required, the animals survive normally. In most cases, as the calf continues to grow and survive for longer periods of time, elevated central venous pressures become apparent. These central venous pressures range from 10 to 20 millimeters mercury. The etiology of the increased central venous pressure is unknown. Studies involving the measurement of atrial natriuretic peptide (ANP) have indicated that there is a disruption in the normal ANP control mechanism, and perhaps this is a contributing factor. Studies of ANP levels in these animals will prove very valuable basic knowledge about this not-well-understood physiology. It is also possible that the various control schemes that are utilized, although providing grossly adequate cardiac output, may

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

affect the long-term regulation of central venous pressure (Mabuchi et al., 1988). Even with elevated central venous pressure, however, it does not appear that control systems and control strategies are a limiting factor in the utilization of temporary or long-term artificial hearts.

Biocompatibility. Thrombosis. In clinical applications, thrombosis or embolus occurred in 14 percent of the 186 applications of the pneumatic artificial heart. It is important to point out here, again, that this was the Symbion-type artificial heart, which may not be indicative of all pneumatic artificial hearts (Gaykowski et al., 1988). Of the three patients who received the Penn State artificial heart, the longest-surviving patient, who lived for 390 days, had one thromboembolic event 10 weeks after implantation. This patient's anticoagulant therapy was modified, and no further thromboembolic complications occurred. Based upon existing data, it would be reasonable to predict that 14 percent of the patients to receive a short-term artificial heart would have a thrombotic event with the Jarvik-type artificial heart. It is not possible to predict the thromboembolic complications with devices of other designs. Thromboembolism is a function of the material that is used in the blood pump, the cleanliness and surface characteristics of that material, the actual geometry within the blood pump (which can affect regions of stasis and blood flow), the presence of cracks or crevices, and the careful matching of materials within the blood pump, including heart valves and associated adjoining hardware. Thrombosis is very design- and manufacturing-sensitive. The only device currently available for clinical application of a total artificial heart is the Penn State device. Very careful attention has been paid to the geometry and surface characteristics, as well as careful design and choice of materials in this device, to avoid thrombosis. Other groups also have designs that are potentially superior to the Symbion/Jarvik-7 system. As previously stated, at Penn State with a pneumatic total artificial heart, 1 animal of 21—approximately 5 percent—that received the device suffered a thromboembolic event causing death. Yet evidence of thrombotic complications and organ infarction was noted in 13 of 24 calves, indicating that thrombosis is still a major complication with total artificial heart devices in animals (Al-Mondhiry et al., 1989). Similar results have been seen by other artificial heart research groups (Nojiri et al., 1989).

Sepsis. In the clinical applications of artificial hearts, sepsis was present in 21 percent of the 186 patients undergoing implantation of the artificial heart (Pae and Miller, 1990). Septic complications have also been noted in the early patients receiving the Jarvik-type artificial heart (DeVries, 1988; Gristina et al., 1988; Kunin et al., 1988). In a series of 24 calves at Penn State, septic complications were documented in 10 animals, thus indicating

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

that sepsis is a major complication with the pneumatic total artificial heart with percutaneous leads.

Hemolysis. In reports from the clinical registry for the application of total artificial hearts, hemolysis was listed as a complication in 7 percent of the patients. Experience at Penn State with pneumatic artificial hearts in calves shows that compared with baseline levels, the hemoglobin was significantly lower and the plasma hemoglobin and serum lactate dehydrogenase levels significantly higher throughout the follow-up period. The platelet count decreased during the first 10 to 30 weeks, but returned to preoperative levels by week 35. Platelet survival levels in these animals in stable condition were normal and within normal limits (Al-Mondhiry et al., 1989). Similar findings have been presented by other groups (Nojiri et al., 1989). The hemolysis levels do not seem unreasonable considering there are four prosthetic heart valves within these devices as well as a large amount of prosthetic materials. The hemolysis levels, although clinically significant, are not unmanageable.

Calcification. All groups utilizing calves and sheep have reported some degree of calcification within their devices (Pierce et al., 1980). Calcification within devices employed in growing animals such as calves has been very severe and a limiting factor in many of the experiments, causing stiffening and perforation of the diaphragm. This calcification does not appear to be as severe in the sheep and goat models (Portner, 1987). The calcification also appears to be a function of the material 's surface characteristics and stress on the material. Results with the clinical application of these devices, for over 600 days, indicate that calcification is not a limiting factor for a two-year device life at the present time. Certainly, in applications of these devices for short-term use, calcification is not significant.

All the current short-term total artificial heart devices appear to have three significant complications in common: bleeding, thrombosis, and sepsis. In the clinical application of these devices, the most frequent complication is bleeding and reoperation in 28 percent of the patients. The next most common complication is infection, occurring in 21 percent of the patients. Thrombosis occurs in approximately 14 percent of the patients, while hemolysis occurs in only 7 percent and is easily managed in most.

Univentricular or Biventricular Assist Devices
Pulsatile Devices (Sac/Diaphragm)

Currently four pulsatile assist devices are available for clinical application in the United States: the ABIOMED BVS System 5000, the Novacor

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

left ventricular assist device, the Pierce-Donachy device presently manufactured by Thoratec Laboratories and Sarns, and the Thermedics (Thermo Cardiosystems) Heartmate device (McGee et al., 1989; Macoviak et al., 1990). There are other ventricular assist devices under development such as the device at the Cleveland Clinic Foundation, the device under development by ABIOMED Corporation, and the device under development by Electrocath Corporation. Ventricular assist devices are also under development in Japan (Atsumi et al., 1989). The Symbion ventricular assist device, which is no longer available, had undergone clinical trials. The most widely used device is the Pierce-Donachy ventricular assist device manufactured by Thoratec Laboratories.

Animal and clinical results. In a multicenter study of 29 patients utilizing heterotopic Thoratec prosthetic ventricles as a bridge to cardiac transplantation, 21 received heart transplants and 20 were discharged from the hospital after a median 31 days. Of the 29 patients, 6 were reported to have had infections during their circulatory support period, but in only 2 did infection cause death; 11 of the 29 patients had severe bleeding complications. Two neurologic events were reported in two patients who were later discharged. In one of the patients who sustained a neurologic event, the drive console was off for 20 minutes the night before transplantation, resulting in insufficient blood flow. In both of these patients, thrombus was found in the explanted pump (Farrar et al., 1988).

The ABIOMED BVS 5000 has been used on more than 170 patients in clinical centers throughout the world. It is currently in clinical trials in the United States in 11 centers. The mean patient age is 46 years, ranging between 7 and 74 years. The mean duration of support is 4 days, with the longest support duration being 30 days. The predominant support mode has been biventricular in 67 percent of the cases. In postcardiotomy support, which is the primary intended use of the system, 45 percent of the patients were weaned with 51 percent of these patients surviving. These numbers are comparable to the registry values (postcardiotomy) of 43 percent and 54 percent, respectively. Complications encountered are quite similar to the overall registry results.

The key features of the BVS 5000 are its low cost and simplicity of use. A primary reason for its low cost is the use of trileaflet polyetherurethane valves. These valves were originally developed under the sponsorship of the National Heart, Lung, and Blood Institute. This technology grew out of the mechanical circulatory support program and is an important element in our efforts to expand the clinical utility of this temporary cardiac support system.

The results from the clinical registry of mechanical ventricular assistance show that bleeding and reoperation are still the major complicating factors in all pneumatic mechanical ventricular assist devices, with an incidence of

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

approximately 30 percent. Renal failure was second with 25 percent, infection was third with 17 percent, biventricular failure occurred in 16 percent of the patients, and respiratory failure occurred in 16. Thrombosis in the system occurred in 5 percent of the patients, and embolus occurred in 7 percent. Thus, it is apparent that the problems that occur in the short-term artificial heart also occur in short-term univentricular or biventricular assist devices when all the devices are considered as a group. Some devices do much better than others.

Technological development. Durability. Durability of these devices for their intended period of application has been very good. Mechanical failure has only occurred in 1.45 percent of those cases reported to the registry (Pae and Miller, 1990).

Control. Devices have been run synchronously and asynchronously both partially full and full-to-empty. There have been no definitive clinical studies showing the relative advantages of one modality over the other. There are theoretical considerations, but there are no data indicating improved survival with one technique over the other.

Biocompatibility. As previously stated, thrombosis, sepsis, and to some degree hemolysis are complications associated with the application of short-term univentricular and biventricular assist devices. Of the pulsatile ventricular assist devices, several designs and materials have been utilized. The Novacor, Symbion, and Thoratec devices all use a smooth segmented polyurethane surface. The device developed by Thermedics (Heartmate) utilizes a textured surface to facilitate the formation and adhesion of a biologic lining. The Heartmate pump diaphragm is fabricated of integrally textured polyurethane, and the metallic surfaces of the pump are textured by using powdered metallurgy techniques. There has been no clinical evidence of thromboembolism in any of the 17 patients for whom the device has been used, nor was there any evidence of thromboembolism in patients who came to necropsy (Graham et al., 1989). It has also been reported that in these patients, plasma hemoglobin levels remained acceptable throughout support. Blood chemistry and hematologic values returned to normal in most cases. One of the patients with this device was supported for 132 days (Nakatani et al., 1989). Thus, with the Heartmate device there is an indication of improvement in the area of thrombosis.

Steady-Flow Devices

Animal and clinical results. There are currently several systems available for clinical application that are of the steady-flow type. These include

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

the Biopump manufactured by Biomedicus, the Centrimed System manufactured by Dolphen, Incorporated, and the Hemopump manufactured by Nimbus, Incorporated. There are also several other devices under development. These include devices such as the spindle pump and the axial flow pump described by Schistek and others (Schistek, 1989). A review of the clinical experience with steady-flow or centrifugal devices shows that there is a slightly higher incidence of bleeding and reoperation with centrifugal devices versus pneumatic devices: 46 percent of the patients had bleeding and reoperation with the centrifugal devices, whereas only 30 percent had bleeding as a complication with the pneumatic devices. There were other slight differences in hemolysis and sepsis, and only a very slight difference in thrombosis and embolus with the two types of devices. If one looks at the outcome of mechanical circulatory support for postcardiotomy cardiogenic shock based upon ventricular assist pump type, 24 percent of the patients with the centrifugal pump were discharged after use of the device and 21 percent of the patients with pneumatic devices were discharged. There does not appear to be a major difference. Careful analysis of all the data within the clinical registry shows that there are some slight differences between devices, but they may be related to the indications for use, i.e., postcardiotomy cardiogenic shock versus staged cardiac transplantation. Yet a review of all of the short-term devices, total artificial heart, biventricular, and univentricular devices, pulsatile and nonpulsatile devices, indicates that bleeding, infection, thrombosis, and to a lesser degree hemolysis all are problems. Other complications such as renal failure and respiratory failure are most likely associated with the poor condition of the patient at the time of surgery. In fact, many of these patients have improved renal and respiratory function with initiation of pumping. If one examines the overall outcome of staged heart transplantation based on all types of ventricular assist devices, 72 percent of the patients with pneumatic devices, 67 percent of those with centrifugal devices, and 86 percent of those with electric devices are discharged. The electric device, in this case the Novacor device, appears to have improved results, but the device is used only for bridge to transplantation.

Summary

When considered as a group, short-term and long-term pneumatic and centrifugal unilateral and bilateral assist devices and total artificial hearts have complications of thrombosis, sepsis, bleeding, and hemolysis, and it is not entirely clear which will be the limiting factor in the longevity of these devices. It is apparent that for short-term use, durability is not a limiting factor and devices appear to be satisfactory for use up to 180 days. Control systems do not appear, on the surface, to have a significant impact on the

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

outcome of the use of these devices. The hemolysis levels associated with the short-term devices, in general, are not life-threatening. Bleeding may not be directly attributable to the device, but due to anticoagulant therapy or prolonged cardiopulmonary bypass. Careful anticoagulant therapy and better patient selection may affect the bleeding and reoperation rate.

Although these complications exist, there are no fundamental physical laws or reasons that limit solutions to the problems of thrombosis, sepsis, and bleeding. Improved materials, as well as improved hemodynamic designs of these devices, can lower not only thrombosis but bleeding, since improved devices will require less anticoagulation therapy. Totally implanted devices as well as new techniques for encapsulating these devices will reduce infection.

Permanent or Long-Term-Use Mechanical Circulatory Support Systems (more than 180 days)
Unilateral Assist Devices
In Vitro and In Vivo Test Results

Several groups in the United States and abroad are now working on permanent electric motor- or thermal-powered ventricular assist devices. These include Nimbus in Rancho Cordova, California, Novacor Division of Baxter Healthcare Corporation in Oakland, California, Penn State in Hershey, Pennsylvania, Thermedics in Waltham, Massachusetts, and various groups in Europe and Japan. Currently, the most advanced device is the ventricular assist device developed by Novacor. The totally implantable left ventricular assist system has demonstrated a two year life in vitro with an 80 percent reliability. Implants in sheep of up to 279 days for the ventricular assist device have been accomplished, and this device has received clinical application for short-term use in patients.

In its use as a temporary assist device, bleeding and reoperation occurred in 42 percent of the patients, infection occurred in 18 percent, and thrombosis and embolism occurred in 16 percent. The outcome of staged heart transplantation with the Novacor system in 41 patients that were implanted is that 22 or 54 percent were transplanted. Of the 22, 80 percent were discharged. Since this device, with a transcutaneous energy transmission system (TETS), will be utilized for long-term support, a prediction of the associated complications can be approximated based upon the short-term use. Infection rates may be improved by the elimination of percutaneous leads.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×
Permanent Total Artificial Hearts

Currently four groups are under contract to the National Heart, Lung, and Blood Institute for the development of permanent electric motor-driven total artificial hearts. Other systems being developed utilize thermal engines to provide energy for blood pumping (Emoto et al., 1988; Butler et al. 1989). At the present time, the thermal systems are several years behind the current electric motor-driven devices. The four groups supported by the National Institutes of Health for development of implantable electric motor-driven artificial hearts are the University of Utah, Nimbus/ Cleveland Clinic, ABIOMED/Texas Heart, and Penn State. There are several non-U.S. systems being developed and they will be briefly described in a later section.

University of Utah System

The University of Utah totally implantable artificial heart system consists of two blood pumps that are similar in design to the pneumatic Utah 100 artificial heart (Khanwilkar et al., 1989). Located between these two pumps is an axial flow pump that will pump a working fluid from one blood pump to the other. This working fluid then displaces blood within the blood pump itself. The axial flow pump alternately pumps in one direction, stops and reverses, then pumps in the other direction to provide systole for both the left and right blood pumps. In the past, this system has had two major drawbacks. One is that an axial flow pump can only be optimized for flow in one direction. That is, the pump efficiency can be good in one direction and but poor in the other, or mediocre in both directions. The second drawback of this system, in the past, has been the ability to balance the output of the left and right pumps. An attempt will be made to overcome the second drawback, balancing of the two blood pumps, by placing a shunt between the left and right atria. The University of Utah system will use a TETS that transmits energy across the intact skin by radiofrequency coupling. The system to be employed will be similar to that developed by Thermedics. Thus far, only the blood pump portion and energy converter have undergone in vivo testing. At the present time, the material used in this blood pump is the segmented polyurethane (Biomer) manufactured by Ethicon, Incorporated, Somerville, New Jersey. Animal results with pumps of this type have shown evidence of thrombosis, sepsis, and calcification (Khanwilkar et al., 1989).

Nimbus/Cleveland Clinic System

The Nimbus/Cleveland Clinic system is based upon the E4T electrohydraulic total artificial heart design. This design is the culmination of many

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

years of research performed by the Cleveland Clinic Foundation and Nimbus. The design uses an electrohydraulic energy converter. The blood pumps utilize pusher plates and flexible diaphragms and all blood contacting surfaces are covered with a seamless biocompatible coating through the biolization process that has been developed at the Cleveland Clinic (Harasaki et al., 1979). Human dura mater tissue valves are used in these devices. The pusher plates are actuated by an electrohydraulic energy converter, the fourth in a series of implantable energy converters developed at Nimbus. The pumping unit is located intrathoracically, consisting of the left and right blood pumps and energy converter. The TETS secondary coil is located subcutaneously over the left thorax. This TETS system, developed by Thermedics, utilizes 160-kilohertz radiofrequency to transmit energy across the intact skin (Sherman et al., 1984). Efforts to date on the development of this system have been focused primarily on the pumping unit (Himley et al., 1990). An electronic controller powers a brushless direct-current (DC) motor which turns a gear pump. The gear pump provides hydraulic power to a hydraulic circuit, alternately actuating a piston from one end to the other. The piston indirectly drives pusher plates which are magnetically coupled to the piston. Blood pumps are alternately actuated. Since the follower is not directly coupled to either pusher plate while one blood pump is being ejected, the other blood pump is free to fill. Hall effect sensors detect the pusher plate stroke position and hydraulic main spool position. These signals provide the fill and eject rates of the left blood pump which are used in the left master control algorithm. The control mode is based on matching the actuator eject rate to the left blood pump fill rate by altering motor speed. It is claimed that the resulting operation provides a simulated Frank Starling behavior. Various components of this system have been fabricated, but the system has not been tested, fully assembled, in vivo. In vivo testing is scheduled for late 1990.

ABIOMED/Texas Heart System

The ABIOMED total artificial heart consists of a thoracic element fitted orthotopically in the thoracic cavity, an abdominally placed battery package, a transcutaneous skin transformer, and an external battery vest. The distinguishing characteristics of the ABIOMED total artificial heart are as follows.

  • Hydraulic power generated by an electrically operated centrifugal pump energizes the blood pumps (Millner et al., 1990). The electrohydraulic approach allows a flexible configuration for optimized blood flow and membrane life.

  • Flow compensation for left-right imbalance utilizes blood as a compli-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
×

ance volume, thus eliminating the use of gas compliance chambers. The left and right sides are alternately pumped while the filling of one side occurs simultaneously with ejection from the other side.

  • Trileaflet valves and seamless blood pumps fabricated from Angioflex, a polyetherurethane, provide long life and smooth thromboresistant surfaces at affordable cost. The blood pump is toroidal in shape and may reduce flexing stresses, thus contributing to a high reliability.

The use of blood as a volume compensation medium for left-right flow imbalance is unique (Kung et al., 1989). The volume compensation chamber is hydraulically in communication with the right hydraulic chamber, while the flexing membrane, which ordinarily is in contact with tissue, in the ABIOMED system is placed in contact with left atrial blood.

The degree of compensation is regulated by the hydraulic fluid flow path resistance, by a design parameter, and by the left atrial pressure. The imbalance flow and resulting left atrial pressure are self-regulating. Higher left atrial pressure results in more fluid displaced from the compensation chamber during right diastole. This means more fluid flowing into the compensation chamber during the following right systole, and so a smaller effective stroke volume from the right ventricle. The lower right-side flow reduces the blood volume in the lungs, reducing the left atrial pressure.

The new geometry integrates well with the energy converter, allowing placement of the pump and valve in the hole in the toroid for efficient use of space. The unidirectional operation of the pump, made possible by the use of a rotary valve to reverse fluid flow, is well matched to the centrifugal pump as well. Efficiencies of 40 percent have been demonstrated. An integrated energy converter has demonstrated the functionality of the new valve in combination with a centrifugal pump.

A new design atrial cuff has been detailed, built, and is about to be tested in vivo. The cuff is rough Dacron on the inside to promote growth of pseudointima, and coated with silicone rubber on the outside to prevent leakage and avoid a need for preclotting. The connector has a smooth Angioflex-coated cannula projecting into the cuff, creating a flow pattern which is expected to avoid pannus overgrowth. The interface between the two mating parts of the connector is the interface between rough and smooth surfaces, and so any initial surface thrombus forming here is expected to attach to the rough surface and avoid embolization. This concept will be tested.

The sensor and electronics have been designed, selected, and individually fabricated for component testing. Critical parameters such as pressure sensor drift are being tested in vitro in a long-term life test. The control algorithm, which makes pump motor speed responsive to filling pressure and beat rate responsive to stroke volume, has been thoroughly tested.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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The ABIOMED program has advanced from the design phase to the current hardware integration and testing phase. During the next year, activities will be concentrated on device evaluation in chronic studies and in vitro testing.

Pennsylvania State University System

The Penn State implantable electric motor-driven total artificial heart system utilizes a brushless DC motor to turn a roller screw mechanism. This mechanism imparts rectilinear motion to pusher plates attached to the ends of the roller screw. Blood pumps are attached to the motor housing. The motor turns six revolutions, turning the roller screw and moving the pusher plate for its complete ejection phase, then the motor stops and counter-rotates, moving the screw and pusher plates through the diastolic phase. Blood pumps are alternately actuated through this mechanism. Energy is transferred through the intact skin by using radiofrequency waves. This system also uses a highly modified Thermedics type of TETS. Both the number of turns per coil and coil configuration have been modified along with a completely redesigned TETS electronics. This system has proven extremely reliable both in vitro and during in vivo experiments (Weiss et al., 1990). An intrathoracic compliance chamber is utilized to provide volume for balancing of the left and right outputs. An automatic electronic control system is employed to balance both the left and right blood pumps (Rosenberg et al., 1984).

The Penn State total artificial heart system utilizes extremely smooth, seam-free blood contacting surfaces currently manufactured from either Biomer provided by Ethicon, or the segmented polyurethane Hemothane, provided by 3M Corporation, St. Paul, Minnesota. Currently, an advanced segmented polyurethane is being developed by DuPont Corporation, Wilmington, Delaware, and will be evaluated by the Penn State group. The shape and design of the blood pump are based upon extensive hemodynamic studies utilizing pulsed Doppler ultrasound, laser Doppler anemometry, and hot film anemometry techniques to determine the velocity field within the blood pump (Baldwin et al., 1988). Particular care is taken in the selection of mating materials and in minimizing regions of stasis where thrombus formation may be initiated. The blood pump and mechanical mechanism for this device in its 100-cc stroke volume design have run for over one year on the mock circulatory system. Animal experiments with this device utilizing only the electric motor and blood pump portion with a sealed compliance chamber have run for 222 days (Rosenberg et al., 1984), and another experiment has lasted for 205 days. Neither of these animals had thrombus or thromboembolic events, nor was sepsis present, a very promising result. In both cases, the electronics have been located outside

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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the animal and connected via a percutaneous lead. More recently, in mid-1990, a complete system has been implanted in two animals. This system consists of completely implanted blood pump, electronics, and TETS. This system currently requires no percutaneous lead, thus eliminating a major nidus for infection. Both of the animals died in less than two weeks, of pulmonary complications; system performance has been very encouraging.

Non-U.S. Systems

A system similar to the Penn State roller screw system is being developed in Japan. It utilizes a drum cam which is similar to the early Penn State device. This Japanese system has undergone some initial in vivo testing (Fukumaga et al., 1989). A system very similar to the Penn State roller screw system is being developed in Geneva, Switzerland. The system utilizes the same roller screw mechanism and very similar blood pump design. Both of these systems are approximately one year behind the U.S. systems in development. Also, more recently Daimler Benz AG has agreed to support the development of a German totally implanted total artificial heart. The design features of its system have not been released.

Summary

In summary, the four U.S. groups undertaking development of permanent total artificial hearts have several common design features. They use radiofrequency TETS, which have been employed in animals by the Thermedics group in left ventricular assist animals and in the Penn State left ventricular assist and total artificial heart animals. The systems have functioned quite satisfactorily, indicating no limiting factors in terms of tissue response to the radiofrequency energy reference.

The University of Utah, ABIOMED, and Penn State devices all utilize segmented polyurethane. Various forms of segmented polyurethane have been tried and are currently under development. The most widely used segmented polyurethane is Biomer, manufactured by Ethicon. This material, initially utilized by Pierce in 1967, is a very old material but still the most widely used material in blood pumps. The Penn State group is working with both 3M and DuPont to develop improved blood contacting material based upon this polyurethane chemistry.

All of the four groups employ electric motor drives to power their artificial hearts. Three of the groups utilize electrohydraulic energy converters, while the Penn State group uses a purely mechanical converter. A two-year reliability has not been demonstrated for these energy converters thus far, but utilizing standard techniques, a life in excess of five years can be predicted for energy converter systems. Blood pump reliability studies

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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have not yet been undertaken, but there is evidence from the Novacor left ventricular assist device that achieving a two-year reliability is quite possible.

All of the groups have identified the need for a control system to balance the left and right blood pump outputs as well as control the overall cardiac output. The Penn State group has demonstrated control of these devices with animal survivals in excess of seven months. The other groups have also demonstrated success in controlling the left-right balance of the blood pumps. At present, it appears that all of the groups working on electric motor-driven total artificial hearts are essentially on schedule with their program plans. The Penn State group has had two in vivo experiments of a completely implanted system. This group has also had two animals with electric hearts survive over six months without thrombotic complications or significant sepsis.

At the present time, non-U.S. systems, those of Japan and Europe, appear to lag slightly behind in development. The group in Geneva, Switzerland, has performed some in vivo experiments with their roller screw system. These experiments were conducted without implanted electronics.

CURRENT TECHNOLOGICAL BARRIERS TO DEVELOPMENT OF A SUCCESSFUL MECHANICAL CIRCULATORY SUPPORT SYSTEM
What Is a Successful MCSS?

Determining the criteria for a successful MCSS is not trivial. Value judgments about cost, quality of life, and overall length of patient survival are all major considerations.

Short-Term Devices (fewer than 180 days)

There has been extensive use of short-term MCSSs, with well over 1,000 applications. When used as a bridge to transplant, these devices have successfully bridged over 50 percent of the patients (Miller et al., 1990). The outcomes of these staged cardiac transplantations are not substantially different than for nonbridged transplantations. A review of the clinical registry, as previously mentioned, outlines the complications associated with these devices. With all types of these devices, there have been fewer than 5 percent mechanical failures in all of the applications.

Although these devices work well when used as a bridge to transplant with survival in over half of the patients, further research is required to reduce the complications associated with these devices. The Food and Drug Administration is currently monitoring several systems under IDEs. When

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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these devices receive their premarket approval, can one say that they are successful? If one compares the current results with today 's MCSSs with the results of the early use of mechanical heart valves, or for that matter early pacemakers, it can be appreciated that devices of these types improve with time. The early pacemakers needed to be pushed around on carts. Patients with these devices were not able to leave the hospital. Today, these devices have progressed to very small, essentially forgettable, systems. Artificial heart valves initially had quite high mortality rates. Even today, patients more than 65 years of age undergoing aortic valve replacement can have as high as a 30 percent mortality at 5 years (Mitchell et al., 1988). It is also important to remember that other cardiovascular devices such as prosthetic blood vessels and heart valves have risks of mortality associated with them that are most significant. Determining the risk of thromboembolism following valvular replacement is an extremely difficult task (McGoon, 1984). The risk varies with valve type, position, age of the patient, and other preexisting disease or condition. The fact that a short-term circulatory assist device uses valves and involves prosthetic materials similar to those utilized in heart valves and vascular grafts would, at the present time, make it seem unreasonable that these devices should provide superior performance to current heart valves and vascular grafts. At the present time, the goal should be to make these devices as safe as existing devices such as heart valves and vascular grafts. It should be noted that both short- and long-term devices, left ventricular assist devices and total artificial hearts, may have considerably more surface area and as many as four artificial valves associated with them.

It is this author's opinion that the performance of short-term mechanical circulatory assist devices in their current stage of development is comparable to that of heart valves in their early stage of development; thus, it is not unreasonable to state that these devices are currently successful but require additional development, as do current heart valves and other cardiovascular devices, to eliminate or minimize all associated complications.

Long-Term Devices (more than 180 days)

Defining a successful long-term MCSS is a somewhat more difficult task than defining a successful short-term device. Fortunately, one way to determine the success of a device such as this is to compare it with existing technology. Currently, the alternative for a patient with end-stage heart disease is cardiac transplantation. Actuarial statistics now show that approximately 50 percent of the patients who receive cardiac transplantation are alive after five years (Kriett and Kaye, 1990). Of the patients who received cardiac transplantation five years ago, less than half are currently alive, so that the actual survival is less than 50 percent at five years for

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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patients receiving a heart transplant (this figure may be as low as 35 percent). Thus, at the current time, it would not be unreasonable to have as a design goal for long-term MCSSs that approximately 40 to 50 percent of the patients receiving these devices survive for five years.

Performance and Reliability
Energy Sources

Currently, all long-term MCSSs utilize electrical energy as a source of power. This may be direct electrical energy for electric motor-and solenoid-driven devices or electric energy converted to heat for thermal systems. At the present time, the most advanced systems are those that are solenoid- or electric motor-driven. The thermal systems under development by Nimbus and the University of Washington are a few years behind in development compared with the electric motor-driven systems. The most practical form of energy source for the long-term devices is external or implanted batteries. External batteries can be used to transmit electrical energy across the intact skin by using a TETS (Rosenberg et al., 1985).

Batteries

Today, the most practical form of batteries for external or implanted usage is the nickel cadmium type. Although silver zinc batteries offer higher energy densities, their cost, potential need for venting, and limited number of recharge cycles make them somewhat impractical for use with these devices. Lead acid or gel cell batteries offer some advantages for external batteries in that their cost is considerably lower than for nickel cadmium, although they are heavier. They also have the added advantage of a voltage which is proportional to the energy in the battery system. Currently, all long-term MCSSs that are being powered by batteries utilize nickel cadmium cells. There is promising new technology with lithium systems that will significantly increase the energy density and reliability of batteries. Honey well Corporation has manufactured test cells and will be providing prototype cells to Penn State for testing in early 1991.

Transcutaneous Energy Transmission System

In the early 1960s, Dr. Schuder (Schuder et al., 1971) began development of a TETS utilizing radiofrequency energy transmission across intact skin. Later, Thermedics continued development of this system for application with their permanent left ventricular assist device (Sherman et al., 1983). There have been other such systems proposed that utilize different

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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coil configurations, such as the system developed by Novacor. Thermedics, Novacor, and Penn State have all conducted in vivo animal experiments with the TETS. The results of these tests show that there is some inflammation and foreign body reaction in the area of the coil. These systems must transmit 10 to 20 watts continuously across the intact skin and have been able to do this satisfactorily. This same method of transcutaneous energy transmission has also been utilized by manufacturers of cochlear implants to transmit the necessary power to operate these devices successfully. These systems have received Food and Drug Administration approval for use.

Energy Converters
Electric Motor-Driven Converters

At the present time, the long-term MCSSs are driven by electric motors or solenoid motors. Motor-driven devices either turn a mechanical linkage arrangement consisting of a cam or roller screw mechanism or, in the electrohydraulic system, power a pumping system that pumps an intermediate fluid to actuate the device. These systems range from low-speed, high-torque systems to very high-speed, low-torque systems. Some of these systems operate at speeds up to 20,000 revolutions per minute, stop and counter-rotate, and accelerate to that speed again. Some of these systems have fewer moving parts than others and range in complexity.

One thing that all of these systems have in common, in terms of electric motor, mechanical linkage, and bearings, is that well-established, sound, fundamental engineering principles can be used to design them. These principles allow the designer to predict the correct motor, mechanical linkage, bearings, and materials for the devices to function satisfactorily for the intended period of use. At the present time, the longest-running system documented is the Novacor solenoid-type electric ventricular assist device. That system has demonstrated an 80 percent reliability for two years (Jaszawalla et al., 1988). Other systems at Nimbus, Penn State, and Thermedics have run in excess of one year, but none has formally been qualified as the Novacor system has.

All of the systems under development currently utilize electronic microprocessor control systems. Ten years ago, these systems were not available and totally implanted artificial heart and circulatory assist devices were only dreams of designers. With the advent of microprocessor systems, very large scale integrated circuits, and hybrid electronics, these systems have become a reality. All of the groups in the United States working on permanent ventricular assist devices have developed miniaturized electronics and in some instances tested them in vitro and in vivo. At Penn State, a completely implanted electric motor-driven total artificial heart has

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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been tested in vitro and in two in vivo experiments involving calves. These were completely implanted systems with automatic electronic control systems and implanted batteries.

The technology in the mechanical systems and in the electronic components is such that it is reasonable to expect 80 percent or more of the electric motors, energy converters, and electronics to function satisfactorily for two years, utilizing current technology. With further development and testing, this could be extended to five years. At the present time, there does not appear to be any technological barrier to developing a battery system, miniaturized electronics, electric motor, and energy converter that will function satisfactorily for five years in 80 percent of the systems run, based upon current engineering predictions.

At the present time, all the systems under development utilize a polymeric material that is in contact with the blood. This polymer may be in contact with the blood in the blood sac or in contact with blood and body tissue through the compliance chamber. All of these elastomeric materials have some degree of permeability. Several groups have been working on laminating low-permeability materials in the blood sac. These have reduced the permeability of the blood sacs and compliance chambers. None of the polymeric materials can provide a truly hermetic seal. Thus, the systems must be capable of operating in an environment that can be losing or gaining mass (CO2, O2, N2, H2O plus others). Although this loss or gain in mass is undesirable, it can be overcome by utilizing an infusion port to make up for lost mass. The systems can be designed from materials that are not affected by moisture. Further development in barrier elastomers may provide for much reduced permeability.

Thus, in summary, for the current energy converters, which include the electric motor, mechanical linkage and hydraulic pump, and the associated electronics and batteries, there do not appear to be any technological barriers that would keep these devices from functioning satisfactorily for two years with current technology; with further research and development, these times could be expanded to provide a high reliability device for five years.

Thermal Heat-Cycle Energy Converters

At present, two systems utilize thermal heat cycles to power mechanical circulatory support systems. Both of these systems are based upon a Stirling thermodynamic cycle. These systems have the potential advantage of being able to run on an implanted heated lithium fluoride-lithium chloride salt mixture providing longer times between recharge than nickel cadmium batteries. These systems in general are more complicated than the mechanical systems, requiring sophisticated insulation to maintain surface tempera-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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tures on the device within physiologically acceptable limits. At the present time, these devices are several years behind electrically powered devices in development.

Blood Pumps

It is somewhat difficult to predict the long-term performance of blood pump sacs or diaphragms, but methods do exist. The prediction of the reliability of mechanical heart valves is more straightforward and easier to accomplish.

Sac/Diaphragm

Currently, all pulsatile long-term MCSSs use a blood pump that consists of a polymeric membrane, forming either a sac or diaphragm. Prediction of the fatigue life of elastomeric materials is difficult. Conventional methods of testing and developing a stress versus cycle diagram are not always fruitful or practical. More recently, investigators are examining these elastomeric materials to determine if they have a threshold tear energy (Capecchi et al., 1989). There is some evidence indicating that the polyurethanes exhibit this type of threshold energy. If they do, it is theoretically possible to design a device that has mechanical stresses such that the system never is exposed to energies above the threshold energy that causes crack propagation. Thus, even though the material may have inherent flaws, these will not propagate due to the low energies. At the present time, it is difficult to predict the stresses in these elastomeric membranes. Calculation of these stresses requires extremely sophisticated computation codes and supercomputers for solutions. These solutions will enable the designer to design a more reliable pump.

As previously stated, the Novacor permanent MCSS has demonstrated a complete system reliability for two years. Pneumatic devices have run at various institutions in excess of two years. Based upon these results, a two year durability for blood pumps is quite reasonable. There is also no reason to believe that careful analysis and redesign of these pumps could not provide for stresses which do not induce crack propagation, thus extending the life of the devices.

Valves

Permanent MCSSs under development use both mechanical and tissue-type valves. Although these valves are all exposed to stresses that are higher than would be encountered when implanted in the natural heart, there

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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are means for predicting the life of these devices. Currently valve manufacturers do accelerated testing which provides information on relative valve durability. Also, finite element analysis can be performed on the valves to determine the stresses imposed on the valve and predict the life. Many of these valves are now reused in animal experiments, and valves have run in excess of two years in these in vivo experiments at Penn State. The durability of these valves appears to be acceptable for a two-year period and may show a durability of five years with additional testing and no further development.

In summary, energy sources, energy converters, and blood pumps including sacs and diaphragms can provide for a two-year durability, and it does not seem unreasonable to predict that a five-year life may be possible with current technology and no further development. Continued testing of the devices must be done in order to accurately determine the reliability of existing systems.

Thrombosis

It is difficult to review all investigators' data relative to thromboembolic events in in vivo animal experiments. A review of the Clinical Registry shows that thrombosis in the system or embolus occurs in roughly 12 percent of patients receiving mechanical circulatory support for all indications. At the present time, none of the long-term MCSSs has undergone rigorous in vivo experiments for preclinical testing. The most advanced system, the Novacor system, has yet to generate sufficient in vivo data to be able to accurately predict the thromboembolic complications of that device. Work at Penn State with implanted electric motor-driven total artificial hearts shows that in eight animals receiving these artificial hearts for durations up to 222 days, two had a thromboembolic event. Thus, thrombosis still poses a significant complication for the use of permanent MCSSs. However, there does not appear to be a technological barrier to solving the problem of thrombosis. Thrombosis is related to the material composition, the surface characteristics of the material, and the fluid mechanics surrounding the material. It can also be activated pharmacologically. The incidence of thrombus complications is much less today than it was 10 years ago. New polymeric materials are now being developed by 3M, DuPont and others. Also under examination is the fluid dynamics within the blood pump. Laser Doppler anemometry studies as well as numerical analysis are being conducted to determine the role of fluid mechanics in thrombosis (Baldwin et al., 1989). There have also been indications from the data of Thermedics that their flocked surface may provide a much reduced thromboembolic rate (Lamson et al., 1988).

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Sepsis

Infection has occurred in as many as 20 percent of the patients listed in the registry. Thus far, all patients and animals run for any significant period (more than two weeks) have utilized a percutaneous lead to provide the driving energy for the device. With the recent use of transcutaneous energy transmission and implanted electronics, the percutaneous lead has been eliminated and there is reason to believe that this will significantly lower the rate of complications due to infection. But clearly, with the sheer amount of prosthetic material implanted, sepsis will always be a serious complication if it involves the device.

Hemolysis

In short-term applications of MCSSs, hemolysis has not been shown to be a significant problem. Although patients may require occasional transfusions, the hemolysis is not usually clinically significant. Animal experiments with long-term MCSSs have also shown results indicating that, with satisfactory heart valves and proper pump function, hemolysis is not a significant complication associated with these devices and does not require transfusion. Improved heart valves and improved pump designs should be able to reduce further the levels of hemolysis.

Calcification

Although calcification has appeared to be a significant complication in growing animals, it is present to a much lesser extent in mature animals. Calves undergoing total artificial heart implantation have more calcification than do mature adult sheep. Very few blood pumps have been run in vivo for over one year. Patients implanted with the Jarvik artificial heart and the Penn State artificial heart survived for more than one year. Calcification was not the cause of failure in either of these devices. Improved materials and/or pump manufacturing combined with reduction of stresses in the blood pumps should reduce calcification. There appears to be no technological barrier to reducing calcification to a level that will not cause device failure in a two year period.

Materials

Various materials are used in the manufacturing of blood pumps. These include various stainless steels, titanium, alloy steel such as Vitalium, polymeric materials such as Delrin, Teflon, polycarbonate, and polysulfone, and elastomers such as polyurethane, Hexin rubber, silicone rubber, and Da-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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cron. With the exception of those components that are in direct contact with the blood intravascularly, the materials used for the MCSSs function with very minimal complications at the present time. Improvements in these materials through either pharmacological treatment or structural changes may impart antiseptic properties to the materials. At the present time it does not appear that there is any identifiable technological barrier to either changing or modifying these materials to improve biocompatibility.

Controls and Electronics

Current long-term MCSSs all take advantage of the latest developments in power and microelectronics. Systems developed to commutate and control these devices have performed satisfactorily both in vitro and in vivo. There does not appear to be any technological barrier that would limit the satisfactory performance of electronics for periods up to and exceeding five years. It is important to note that many similar systems utilized in automobiles and aircraft have performed their mission satisfactorily for comparable periods of time.

Bleeding

Bleeding has been shown to be the most prevalent complication in the application of short-term MCSSs listed in the registry. The bleeding that is associated with the application of these devices is not necessarily unique to these devices. It will occur in patients undergoing long cardiopulmonary bypass times or patients normally hemodiluted or in compromised physical condition. In animal experiments at Penn State utilizing permanent MCSSs, bleeding is still a complication. Bleeding occurs in approximately 25 percent of animals undergoing implantation of ventricular assist or artificial heart devices. In the artificial heart devices, there are longer suture lines and thus bleeding becomes more probable. Improved techniques and surgical procedures have reduced the incidence of bleeding in animal experiments over the past decade. Although the incidence of bleeding as a major complication has been decreased, there does not appear to be any fundamental technological reason why it cannot be further reduced. It is extremely doubtful that it will ever be eliminated, any more than it is eliminated as a complication in any major surgery (5 percent of open heart surgery cases return to the operating room for bleeding), particularly for those requiring cardiopulmonary bypass.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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EFFECTS OF NEW OR EMERGING TECHNOLOGIES ON IMPROVEMENT IN MECHANICAL CIRCULATORY SUPPORT SYSTEMS

Several new or emerging technologies will have a positive impact on development of MCSSs. These include materials development, electronics development, magnetic materials development, and supercomputers.

Materials Development
New Plastics and Polymers

One of the most widely used polymers in mechanical circulatory support systems is polyurethane, specifically Biomer, manufactured by Ethicon. This material, first developed by DuPont, is now some 20 years old. At the present time, 3M is developing a polyurethane similar to Biomer in a joint effort with Penn State. Most recently, DuPont has made a decision to begin development of improved biomaterials, specifically an improved Lycra- or Biomer-like polyurethane. Both of these companies have highly capable individuals to perform the necessary development. The interest of these companies in developing new biomedical elastomers for blood contact is very exciting. These new elastomers will have design goals of being more biocompatible and more fatigue resistant, along with ease of fabrication. Potentially, there are thousands of polymeric materials yet to be developed. The improvement in existing polymers and the development of new polymers through research and development should have a positive effect on development of MCSSs. Elastomers can also be modified by texturing the surface or chemically altering the surface.

Surface Modifications

Surface modification of existing and new polymers is another method of improving biocompatibility. Bonding of a heparin-like substance to the surface of the material can improve the thrombogenicity of polymeric materials. Ion implantation can be performed on these materials to change their surface structure to improve mechanical properties as well as biocompatibility. Companies such as Spire Corporation have been leaders in the area of ion implantation in metal and polymeric materials. Surfaces may also be coated with LTI pyrolytic carbon. Surface charge and surface energy may play a role in thrombogenicity and also may be altered through surface modification.

New plastics which have recently become available for implant such as polysulfone have had a positive impact on MCSSs. Penn State has replaced

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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its devices' polycarbonate components with polysulfone, which has improved durability without changing biocompatibility. Plastics can also be used to form composites with substances such as carbon fiber, boron fiber, Kevlar fiber, and others. These composites have excellent strength-to-weight ratios and can also be manufactured of compatible biomaterials.

Improved Metals, Ceramics, and Composites
Improved Metals

Various ferrous and nonferrous metals are utilized in the energy converters and blood pumps of MCSSs. These include traditional metals such as the stainless steels and titanium alloys as well as some of the less traditional superalloys.

A relatively new class of metals, amorphous metals, is a new family of engineering materials. Amorphous metals are produced by cooling molten metals so quickly that they do not form regular crystalline structures but rather are frozen in random atomic patterns similar to those found in glass. These materials can improve motor performance. These amorphous metals or metallic glasses are being developed by Allied Corporation in the United States and other companies in Japan and Europe. Already these amorphous metals have begun to compete with the metallic strips and large ferrite cores in magnetic devices operating from 100 to 200 kilohertz. They are also being used in magnetic components for switching power supplies, in transducers for phonograph cartridges, and in magnetic shields for blocking electromagnetic interference. This new technology may also impact positively on the motors and solenoids in electrically powered MCSSs.

Surface Treatments

Surface treatments and coatings have been recently applied to various metals. Ion implantation is one method of changing the physical and chemical properties of material surfaces. Today ion implantation is used to selectively increase corrosion resistance, hardness, wear resistance, and other surface sensitive properties of metal parts without affecting dimensions.

There are also thermally sprayed coatings. Thermal spraying has become much more than a process for rebuilding worn metal surfaces. Thanks to sophisticated equipment, precision control can now be factored into the design process. Materials can be combined to produce the required surface quality such as wear resistance, solderability, or thermal barrier characteristics. Union Carbide Corporation has a new D-gun coating process as well as the traditional plasma coating process. These processes can be used to deposit material such as tungsten carbide, chromium carbide, tungsten tita-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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nium carbide, aluminum oxide plus titanium dioxide, chromium oxide, nickel, nickel chromium, cobalt-based alloys with aluminum dispersion, plus others. Companies such as Perkin Elmer and Norton Industrial Ceramics are developing new coating techniques.

Surface treatments can also be used to form various imperfections or irregularities on the surfaces of metals or ceramics to promote such phenomena as improved heat transfer of boiling or condensation. These would have application for devices such as a two-phase fluid compliance chamber. This is a compliance chamber designed to operate at a constant pressure utilizing a material that goes from saturated liquid to saturated vapor at constant temperature and pressure. This then is a volume change under constant pressure and can be utilized to compensate for changes in blood volume within the device (Lamson et al., 1988).

New Ceramics

New ceramics made of materials such as alumina, aluminum silicate, carbon/graphite, silicone nitride, titanium diboride, boron nitride, Macor from Corning Glass, partially stabilized zirconia, and others all have promising applications for mechanical components in MCSSs.

One of the newest applications for these ceramics involves what are referred to as hybrid bearings. These bearings utilize conventional steels for the races such as carbon steel 52100 and stainless steel 440C, but utilize ceramic balls made of materials such as silicone nitride. These hybrid bearings have improved life.

New Composites

Literally thousands of composite material combinations are possible today (Schwartz, 1983). These composites are a matrix consisting of at least two distinct components, one the binder that contains the major structural elements of the fibers. Most composites to date have used a relatively soft matrix, a thermosetting plastic of a polyester or epoxy type. These composites can offer advantages in manufacturability of both rigid and flexing members of the devices. It may be possible to use fiber reinforcement in a flexing diaphragm to improve fatigue resistance. The binders can be reinforced with various fibers such as aluminum, steel, E-glass, S-glass, HT graphite, boron, various grades of Kevlar, and other materials. These composite materials are being used extensively in the aerospace industry, and further developments in this area will undoubtedly help to improve durability of MCSSs.

Most recently, ceramic metal composites have been developed. At present, this new family of hard, lightweight, and tough ceramic metals was devel-

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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oped for military armor (Ashley, 1990). It consists of aluminum and boron carbide. This material would have application in cases or housings for mechanical circulatory support systems.

Electronics Development
New Power Devices

Over the past two decades there have been dramatic developments in electronics components. New power devices that switch much more rapidly and have much lower on-resistance have been developed. There will be new, even faster switching, lower on-resistance power switching devices becoming available within the next year. These will improve the efficiency and reliability of MCSSs.

New Microprocessors

Larger and faster microprocessors are becoming available almost yearly and will greatly simplify the current systems.

Hall Effect Devices

Improved Hall effect devices have been manufactured by various companies such as Honeywell. Their Hall effect sensors have gotten smaller and more reliable with improved performance specifications. New and improved devices will be forthcoming in the near future.

Room-Temperature Superconductors

Major strides have been made in approaching room-temperature super-conductors, and work on them continues. Even if just an order-of-magnitude change is accomplished in existing conductors, this will have a very significant impact on MCSSs. Major losses occur in these devices due to the I 2R losses in the motors and leads. In summary, electronics development should have a major positive impact on MCSSs in the very near future, in terms of increased reliability, reduced size, and less power utilization.

Magnetic Materials

In the 1970s, Alnico was the magnetic material of choice for brush-type DC motors. Late in the 1970s, brushless DC motors were developed but still utilized Alnico metals. In the late 1970s, improved magnetic materials

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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were developed that utilized rare earth materials such as samarium cobalt. Energy products approaching 30,000,000 Gauss Oersted were obtained with this material. More recently, neodymium iron magnets have been developed that produce an energy product in excess of 30,000,000 Gauss Oersted. These improved magnetic materials mean smaller and lighter motors and better magnetic coupling in solenoid devices. Research continues for improved magnetic materials. Any improved magnetic materials would have a positive impact on MCSSs. They would reduce the size and weight of the device, and might also improve overall performance.

Supercomputers
Computational Fluid Dynamics

Supercomputers such as the Cray system have had and will, in the near future, have a significant impact on the development of MCSSs. These systems can be used to solve extremely complicated, nonlinear partial differential equations that may describe stresses in the materials or fluid mechanics. These are extremely important studies in terms of (1) understanding the fluid mechanics within the blood pump and (2) determining the stresses in the various components of the system. At the present time, it is not possible to solve a three dimensional unsteady, non-Newtonian turbulent flow within these blood pumps. Thus, it is extremely difficult to know and understand the fluid mechanics that are occurring in the device and the contribution to thrombosis, hemolysis, and the mechanical stresses within these devices. Through the use of new codes and supercomputers, solutions of this problem will yield basic information related to fluid mechanics and thrombosis.

Numerical Analysis Techniques

The ultimate longevity of the elastomeric diaphragms and other mechanical components in these blood pumps relies on an accurate prediction of the stresses imposed on the device during operation. The determination of these stresses involves the solution of difficult differential equations. New supercomputers and new codes can be utilized to solve these differential equations. These solutions can then be used to do optimization of the size and shape of the blood pump to provide for minimum stresses and minimum hemolysis and thrombosis related to the mechanical motion and fluid mechanics of the device.

Summary

Developments in new materials, electronic components, magnetic materials, and supercomputers should all have a positive impact on MCSSs. Not

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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only will the new materials and electronic components provide for smaller and more efficient and reliable devices, but the advent of new polymeric materials or surface-improved materials should also yield reduced thrombosis. New mathematical models solved on supercomputers will give a better basic understanding of the role of mechanical stresses and fluid mechanics in thrombosis, hemolysis, and mechanical component failure. This basic knowledge can be utilized to design and optimize improved devices.

SPIN-OFF TECHNOLOGIES
Materials and Design

Research on mechanical circulatory support has generated a pool of individuals with unique expertise in the area of artificial organs. The expertise of these individuals can be utilized in the development of other devices such as grafts, valves, new biomaterials, biosensors, and implantable battery technology.

Grafts

The technology related to materials and blood flow within MCSSs can be applied to the design of new and improved vascular grafts. New biomaterials, manufacturing processes, or surface modification techniques can be used for these grafts.

Valves

Researchers working on the development of mechanical circulatory support systems are working on manufacturing polymeric trileaflet heart valves. ABIOMED currently uses a polymeric trileaflet valve that their personnel have designed and constructed for their short-term MCSS. Researchers at the University of Utah and Penn State have also manufactured polymeric heart valves (Wisman et al., 1982). As these valves are further developed, they may find clinical application as prosthetic heart valves. They potentially could offer improved biocompatibility over mechanical and tissue valves at a reduced cost.

Biomaterials

Certainly, any biomaterial developed for MCSSs could be utilized in other implant applications. There have really been no new major biomaterials developed in the past 10 years. Increased emphasis should be placed on the development of new biomaterials that would be applicable to mechanical circulatory assist devices and other biomedical applications.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Biosensors

Researchers associated with mechanical circulatory support systems are developing biosensors that can be used to control devices such as the artificial heart. These biosensors will sense quantities such as pH, carbon dioxide, carbon monoxide, and oxygen tensions within the body. These biosensors will have uses in artificial organs such as liver, kidney, and lung. They would also have application for incorporation into catheters that can be used for monitoring of hospital patients in intensive care units.

Battery Technology

The Honeywell Energy Systems Division has identified the biomedical market as one they would like to develop a battery for. Honeywell has previously developed a lithium technology primary battery that is utilized in the implantable defibrillator. Honeywell Energy Systems is currently working on the development of new lithium rechargeable technology for use with MCSSs. This battery technology, if developed, would be used for other high-energy, high-reliability applications such as in aerospace and other medical areas.

Drug Actions

Artificial heart animals and patients provide excellent models for testing the actions of various drugs. The effects of these drugs on the vascular system can be studied while the heart is controlled by the researcher. This model can then be utilized to understand more clearly the cardiac and vascular component actions of the drugs.

Development of Transcutaneous Energy Transmission Systems

Development of transcutaneous energy transmission has already been spun off into use into the cochlear implant, as previously described. This technology would have application for other implanted artificial organs that require high energy levels.

Much of the technology that is developed for MCSSs can be used for other artificial organs or biomedical applications. Also, developments in battery technology, biomaterials, and biosensors will have uses in other high reliability situations such as aerospace applications.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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SUMMARY
Current Status of Mechanical Circulatory Support Systems
Short-Term Devices

Several short-term ventricular assist devices are now available to clinicians under IDEs. These include the Thoratec pump, the Thermedics pump, the ABIOMED system, the Novacor system, the Sarns Centrimed system, and the Biomedicus pump. Usage of these short-term ventricular assist devices has been outlined elsewhere and is covered extensively in the Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart. It should be noted that complications associated with this class of devices, in general, include bleeding, infection, thrombosis, and to a lesser extent hemolysis. It is also quite important to note that some of the devices have much better results in certain areas than others. For example, the Thermedics device has been utilized in 17 patients without thrombosis or thromboembolic events. Although this is a small number of patients, the results appear encouraging. Also, a careful look at the registry data shows that a particular device may do better than the general population of devices. The success rate for these devices continues to improve with time, and there appears to be great interest in getting more of these devices into use.

At the present time, the only short-term total artificial heart approved by the Food and Drug Administration is the Penn State heart. This device has been utilized in three patients, the longest of whom survived for 390 days. The clinical indications for the use of a short-term total artificial heart have not been well established. It appears that in most instances, biventricular support or univentricular support is adequate for short-term bridge to transplant applications. With biventricular and left ventricular assist devices as successful as they are, it is doubtful that there will be an increased use of the short-term total artificial heart.

Long-Term Mechanical Circulatory Support Devices

Long-term or permanent ventricular assist devices are coming quite close to clinical application. The system developed by Novacor has demonstrated a two-year life with an 80 percent reliability in vitro. Preclinical testing in vivo will begin shortly, and clinical trials under an IDE will also be beginning in the next one to two years. The Novacor system has been utilized as a short-term device clinically with results essentially similar to the average registry results. Other research groups, such as ABIOMED, Penn State, Thermedics, and the University of Washington, are all pursuing development of long-term ventricular assist devices. Devices from Nimbus, Penn

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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State, and Thermedics have undergone limited in vitro testing and have all been utilized in vivo. Experiments at Penn State have been conducted utilizing transcutaneous energy transmission with a completely sealed system in the calf.

Long-Term Implantable Total Artificial Hearts

Four groups in the United States are now working under contract on long-term electric motor-driven total artificial heart devices: ABIOMED, Nimbus, Penn State, and the University of Utah. ABIOMED, Nimbus, and University of Utah have completed initial designs and have begun in vitro testing of various components of their systems. Penn State has manufactured a complete electric motor-driven total artificial heart system that transmits energy across the intact skin by inductive coupling. The system is completely sealed and totally implantable, has undergone in vitro testing, and has been utilized in two calf experiments. This system is currently in a state of development that is equivalent to the development of long-term ventricular assist devices, with the exception of the Novacor system, which is the most advanced. All of these systems have their relative advantages and disadvantages in terms of size, efficiency, and reliability, and further testing is required to determine the best system.

Prospects for the Future of Mechanical Circulatory Support Systems

Prediction of future prospects for MCSSs can be done with a certain degree of confidence for the next three to five years. When predicting for the next 5 to 10 years, one needs to be more cautious; in predicting the prospects for the next 10 to 30 years, one must be extremely cautious. Looking back at medical device and device-related technology in the early 1950s, it is doubtful that many would have predicted then the great usage of heart valves, pacemakers, implantable defibrillators, and vascular prostheses available today. In the 1950s, the first pacemaker had to be pushed around on a cart by the patient. Twenty years ago, patients were still changing or charging batteries in their pacemakers. Then new higherenergy-density primary cells and lower-energy-requiring C-MOS electronics made charging and changing batteries a thing of the past. Today there are smaller, lighter, programmable adaptive pacemakers. The usage of heart valves has expanded and the results have improved.

In general, if one looks at the history of MCSSs and plots survival times in animals and in patients versus time, one sees a very progressive increase in both animal and patient survival times.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Three to Five Years

In the next three to five years, short-term ventricular assist devices should see more widespread use. Sarns/3M Healthcare Group will be making the Pierce-Donachy pump available under an IDE within the next year, and it is reasonable to predict that other companies will attempt to expand their usage under IDEs. Thus, the use of these devices should continue to increase gradually. It is doubtful that the use of short-term total artificial heart devices will expand due to the success that is occurring with the current left heart assist devices. In the next three to five years, long-term ventricular assist devices will continue to be tested for preclinical and clinical application. Novacor should be able to complete in vivo studies on its system and begin initial clinical trials within the next two to three years. Thus, clinical application of the Novacor system could occur within the next five years. Other systems being developed for long-term application may undergo in vitro testing to qualify for in vivo testing prior to clinical application within the next five years. Permanent total artificial heart devices currently under development will begin initial in vivo experiments within the next three to five years, and some fairly extensive in vivo and in vitro studies should have been completed on all four of the systems being developed under government contact.

Five to Ten Years

It is reasonable to assume that there will be the same trend in usage of short-term left ventricular assist and total artificial heart devices within the next 5 to 10 years. Perhaps improvements in the short-term left heart assist devices will result in more usage for cardiogenic shock support. Within the next 5 to 10 years, the permanent left heart assist system of Novacor should be well into clinical trials. Other groups manufacturing devices, such as Nimbus, Penn State, ABIOMED, and Thermedics, should within the next 5 to 10 years complete their animal in vivo studies and begin human in vivo studies. Within the next 5 to 10 years, permanent total artificial heart devices should be well on the way to becoming finalized designs. The current contracts call for the beginning of preclinical testing within the next five years. This would mean that the groups should have completed all of their preliminary in vitro and in vivo testing and have begun extensive reliability testing and animal studies. By 10 years from now, the first of these devices should receive some clinical application. Thus, it would seem reasonable to predict that within the next 10 years a permanent total artificial heart will be implanted in a human. This device should have as a minimum an 80 to 90 percent reliability for two years.

Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Ten to Thirty Years

Predictions for the next 10 to 30 years become much more difficult. Within the next 10 to 30 years, new materials should become available that will reduce or eliminate the complications associated with MCSSs. Almost surely new magnetic materials, new electronic components, and better conductors all will enable these devices to be improved. New electrochemical energy sources should become available and should be able to be incorporated into existing designs. Within the next 30 years, these devices should be available for widespread use and provide a satisfactory lifestyle, with five-year survival rates in excess of 50 percent.

It is always worrisome to make predictions about the future and much more so when they are made in writing. With that in mind, this author has attempted to be as conservative as possible. Looking at the history of mechanical circulatory assist devices, looking at the status today, and looking at the progress that has been made, one should feel fairly comfortable with predicting their widespread usage in the future. This is not to predict that these devices will be without problems of bleeding, infection, and thromboembolic complications, but that such problems will be much reduced and the devices will provide a satisfactory lifestyle for patients in the future.

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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Suggested Citation:"Appendix C: Technological Opportunities and Barriers in the Development of Mechanical Circulatory Support Systems." Institute of Medicine. 1991. The Artificial Heart: Prototypes, Policies, and Patients. Washington, DC: The National Academies Press. doi: 10.17226/1820.
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Next: Appendix D: Epidemiology of End-Stage Heart Disease »
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A significant medical event is expected in 1992: the first human use of a fully implantable, long-term cardiac assist device. This timely volume reviews the artificial heart program—and in particular, the National Institutes of Health's major investment—raising important questions.

The volume includes:

  • Consideration of the artificial heart versus heart transplantation and other approaches to treating end-stage heart disease, keeping in mind the different outcomes and costs of these treatments.
  • A look at human issues, including the number of people who may require the artificial heart, patient quality of life, and other ethical and societal questions.
  • Examination of how this technology's use can be targeted most appropriately.
  • Attention to achieving access to this technology for all those who can benefit from it.

The committee also offers three mechanisms to aid in allocating research and development funds.

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