Artificial Hearts and Cardiac Assist Devices
ARTIFICIAL HEARTS AND CARDIAC ASSIST DEVICES•••
In 1964 the U.S. Congress budgeted $581,000 to establish an artificial heart program at the National Institutes of Health (NIH). This was the first large-scale effort by any nation to support systematic research into the development of an artificial heart. The effort to build a reliable, totally implantable artificial heart has yielded marginal results. But even though an effective device does not exist, the artificial heart has, since the 1960s, been at the center of a heated ethical, economic, and policy debate. The debate over the wisdom of building and testing an artificial heart has also served as a paradigm for debating the future of expensive technologies in the U.S. healthcare system.
Scientists and physicians in many countries have dreamed for centuries of curing fatal heart diseases by creating a mechanical substitute. Technological advances during the 1960s in engineering fields such as metallurgy, fluid dynamics, electronics, and computer modeling made some scientists think that it might be possible to actually construct such a device. The emergence of the kidney dialysis machine, which could mimic the functions of a human kidney, created a fundamental change in attitude in medicine about the feasibility of building an artificial heart. In the late twentieth century, the quest for the Totally Implantable Artificial Heart (TAH) was once again the catalyst for other technological advances; except for the TAH, the success of the artificial heart program to date is still up for debate.
The Total Artificial Heart
Constructing an artificial heart requires materials such as metals, ceramics, plastics, and polymers that are lightweight and durable. At the same time, these materials must be biologically inert. They must work synergistically with other body systems and not trigger attacks by the body's natural system of immune defenses that would lead to the disruption of the circulatory system and, ultimately, death. An artificial heart also requires sufficiently smooth surfaces so as not to disrupt blood flow through the heart or damage fragile blood cells. A TAH needs a power source that can maintain an efficient and steady stream of energy for long periods of time while being small enough to fit completely inside the body. Both the pump and the power source must be capable of responding to changes in position, temperature, and pressure associated with the needs of the person using the machine.
The decision to launch a program to build a totally implantable heart had its roots in a series of exploratory meetings held during the 1950s at the NIH (Shaw). Enthusiasm for undertaking the research accelerated in the 1960s as physicians and engineers began to build and successfully use the first heart-lung machines, external pumps that could be used to support blood circulation in the body. After a few hours, these machines damaged the blood cells (Zareba). Still, the heart-lung machine was a crude, partial artificial heart that inspired physicians to think that perhaps a permanent device was not beyond reach.
Moreover, as the U.S. space program began to enjoy success, optimism grew in both scientific and government circles about the feasibility of taking on large-scale technological challenges. Many in government were impressed with the productive results being secured in the space program and the military from centrally funded, programmatic research. U.S. physicians and biomedical scientists saw themselves as being able to overcome the many technical obstacles through hard work, directed budgets, and targeted programs. The space program had as its goal putting a man on the moon before the end of the 1960s. The artificial heart program launched at the NIH in 1964 set as its goal the testing of a total artificial heart in a human being by Valentine's Day, February 14, 1970 (Bernstein).
The goal of implanting an artificial heart by the end of the 1960s was not attained. A major hurdle was the development of an energy source capable of providing long-term power to an artificial heart—while fitting inside the body. Not only was progress slow but, during the time artificial heart researchers were trying to overcome the large number of technical challenges that confronted them, an alternative to the mechanical heart appeared: cardiac transplantation. Ironically, the rationale for recent clinical trials of artificial hearts is to find a replacement for the now common cadaveric heart transplant. The increased need for organs and a stable donation rate are the main reasons why there has been renewed interest in total artificial hearts.
While Denton Cooley did implant a crude mechanical heart in a human recipient at Baylor University College of Medicine in 1969, most of the device, including the power source, remained outside the body. He explicitly stated that his sole motive for using this primitive, untested device was the desperate hope that it might help an imminently dying patient live long enough for a donor heart to become available for transplant. According to Michael DeBakey, Cooley did not believe the device he implanted was a permanent replacement for his patient's heart.
This attempt to use an artificial heart as a bridge to keep a patient alive in the hope that a transplant could be done took place without the approval of Cooley's superiors or any government agency. The recipient, Haskell Karp, died shortly after the implant. Cooley's decision set off a storm of controversy within his medical center. Karp's wife later filed suit against Cooley for failure to obtain proper informed consent to the experiment. Texas courts held that since the procedure was experimental, there was no agreed-upon informed-consent standards that governed artificial heart implant surgery and dismissed the suit.
The power source for the TAH has been a persistent problem. Some researchers in the late 1960s believed that the problem of how to power a TAH could be solved by using a small, implantable capsule of plutonium. In 1972 a specially convened NIH panel, the Artificial Heart Assessment Panel, conducted the first governmental review of such technology. It concluded in 1973 that while the "advent of the totally implantable artificial heart" would be "an earthshaking event," the use of atomic power to drive a mechanical heart posed unacceptable radiation-exposure risks to the public health (Artificial Heart Assessment Panel, 1973, p.187). Current devices rely on access to external power and small batteries. More than thirty years after Cooley's first implant, battery technology still has proven to be a limit on how long a patient can safely remain on an artificial heart.
The Artificial Heart Goes Private
In 1976, Willem Kolff (a physician and the inventor of kidney dialysis and one of the first artificial hearts) and some of his Utah colleagues formed a private company, Kolff Medical Associates, to attract venture capital to support their research. In order to interest private investors, they had to create a marketing program for their mechanical heart. The decision to proceed with a private company constituted a first step into the emerging and often ethically controversial world of public-private partnerships intended to advance medical research.
After further testing and redesign of models previously tested in calves, Clifford Kwan-Gett, Willem Kolff, and later Robert Jarvik managed to use a Jarvik-7 to keep some animals alive for as long as eight months. In 1980, Kolff Medical Associates applied for permission from the institutional review board (IRB) of the University of Utah Medical Center to try the device on a human being. They also sought permission from the U.S. Food and Drug Administration (FDA), which, since 1976, had authority to regulate the testing and marketing of medical devices. While awaiting approval, members of the Utah artificial heart group traveled to Philadelphia and conducted a series of three practice implants of a Jarvik-7 heart on brain-dead patients at Temple University Medical Center. Permission from family members to use the cadavers was obtained by Jack Kolff, Willem Kolff's son, then a surgeon at Temple.
After many weeks of resubmissions and revisions, the IRB at Utah and the FDA granted approval to undertake a series of seven implants of a Jarvik-7 heart in human beings at the University of Utah. The subjects were to be patients with very severe, life-threatening congestive heart failure resulting from cardiomyopathy, a poorly understood condition that causes irreversible fatal damage to the muscle of the heart (Scherr et. al.). Kolff and Jarvik, who had renamed their company Symbion, selected a young surgeon, William DeVries, to perform the first implant in a human recipient.
The Experiment on Barney Clark
Barney B. Clark, a retired dentist who had been admitted to the University of Utah Medical Center on November 29, 1982, with cardiomyopathy, was deemed to be an ideal candidate for the first implant of the Jarvik heart (Fox and Swazey) as he was educated, enthusiastic, and had a very supportive family. He signed the eighteen-page consent form the night he was admitted to the hospital. When his heart began to fail on December 1, he was taken to the operating room, and after a nine-hour operation he became the first human being to receive an artificial heart intended as a permanent replacement for his own.
Jarvik and DeVries spent many hours speaking with the media about the operation, the device, and their patient's health status. In the days after the implant, the healthcare team made many optimistic pronouncements to the media about Clark's chances for survival. But Clark followed a very rocky course during the 112 days he lived with the Jarvik-7 device. He suffered a wide range of complications that required three additional surgical procedures. After a few weeks on the machine, his emotional and cognitive state deteriorated severely, and on more than one occasion, he asked that the artificial heart be turned off. This was not done. After his death, more than 1,300 people, including political figures, members of the governing council of the Latter-Day Saints (Mormon) Church, of which Clark was a member, many of his doctors, and media representatives from around the world attended his funeral in Seattle, Washington.
DeVries and the Utah group pronounced the Clark experiment a success. They had kept a man alive in the final stages of heart failure for well over three months. But the IRB at Utah, troubled by the many complications that had arisen during the experiment, asked for many changes and clarifications in the research protocol before giving DeVries permission to try another implant. Among other things, the Clark experiment raised questions about the adequacy of informed consent of potential recipients. Could those facing certain death really be said to choose? And were those conducting the research so enthusiastic and hopeful about its prospects that they could not provide a realistic picture of the risks and dangers inherent in the experiment (Fox and Swazey)?
Between 1984 and 1987, four more implants were done using artificial hearts as permanent replacements for the human heart. William J. Schroeder received his implant of a Jarvik heart on November 29, 1984, less than two months after the IRB at Humana-Audubon gave its approval. Schroeder initially did well on the heart, but within nineteen days he suffered a stroke. During the course of the next 620 days he spent on the device, he had three more strokes; the last brought about his death. The other recipients of total artificial hearts, two at Louisville, one in Sweden, and one in Arizona—all experienced similar difficulties and ultimately died. It became clear from these experiments that the Jarvik-7 was not suitable for use as a permanent replacement device.
In January of 1988 the new director of the National Heart, Lung, and Blood Institute, Claude Lenfant, decided to cancel the NIH program to build a total artificial heart. The recent experience with artificial hearts, he believed, clearly indicated that such devices could be best used to assist failing hearts or for temporary use until a transplant could be found. Lenfant argued that a totally implantable artificial heart was still at least ten years away and might well wind up benefiting a relatively small number of patients at great cost. The threat of shutting down research on the TAH created a whirlwind of political protest in Congress. Legislators from states such as Utah and Massachusetts, where heart research was being conducted, fought to block Lenfant's plan. By the end of 1988, $20 million had been awarded to four centers to continue this research.
In July of 1991, the National Academy of Sciences' Institute of Medicine issued a study in which they recommended continued federal funding for both Left-Ventricular Assist Devices (LVADs) and TAHs. They predicted that a reliable LVAD should become available in the late 1990s and a TAH by around 2005 (Institute of Medicine). Federal funding for research on both permanent and temporary artificial hearts continued.
In July of 2001 the first Totally Implantable Artificial Heart replaced Robert Tools's own heart. Abiomed, Inc., started the controversial clinical trial of the Abiomed artificial heart. The FDA has approved fifteen patient implants.
The Left-Ventricular Assist Device
The left chamber, or ventricle, of the human heart does the greatest share of the work of circulating blood throughout the body. Heart attacks and other forms of heart disease frequently damage this portion of the heart. An LVAD is a pump capable of supplementing the function of the left ventricle, thus allowing a weakened or damaged heart to support life. It does not require an implantable power source and its design can be simpler since it does not have to duplicate all the functions of a heart for prolonged periods of time.
In the United States the ventricular assist device is used primarily for three groups of patients: those who cannot be weaned from cardiopulmonary bypass after a cardiac procedure; those who have an acute heart attack that results in cardiogenic shock; and the largest group, those who have end-stage heart disease and need some support while waiting for a heart transplant. In several European countries the LVAD is used as destination therapy. This is prohibited in the United States because the FDA has only approved the device as a bridge to transplant.
Starting in 1973, the NIH spent approximately $10 million per year over the next decade and a half on research on LVADs for damaged hearts. The first implant of an LVAD in a patient who could not be weaned from bypass was done in August of 1966 (Goldstein et al.). In the ten days after surgery the patient's continued improvement allowed her to be successfully weaned from the pump (DeBakey). It was not, however, until the early 1990s that a number of universities and private companies in a wide variety of countries undertook formal clinical trials of LVADs. Currently LVADs are a relatively common treatment for patients who are candidates for heart transplantation.
Ethics and Mechanical Hearts and Cardiac Assist Devices
The history of artificial heart research and use raises many ethical issues. Among these there are several issues that are especially important. These issues are both specific to the artificial heart and also apply more generally to all forms of new and expensive high-technology healthcare.
The use of human subjects in a clinical trial is one of the most important dilemmas of artificial heart research. The existing protections for persons who participate in medical research are informed consent and review by local committees of scientists (IRBs) of research proposals. The history of artificial heart research has called into question the adequacy of both protections.
Patients asked to serve as subjects in the use of artificial hearts and during the development of LVADs are extremely vulnerable. They face certain death if the device is not implanted. In many cases their heart failure came about suddenly and unexpectedly, and in others the opportunity to receive a device is not introduced until the patient is facing imminent death. For many of the subjects, the complexities of the research and the rigorous post-implant monitoring of the device in the past have been extremely intimidating and continue to be. Moreover, subjects may hear the risks and benefits of participation only from researchers who themselves have a powerful interest in wanting their work to proceed. Those who sought subjects to receive artificial hearts in past trials did so as both clinician and researcher to the recipients of the device, generating a strong conflict of interest.
The threat of imminent death tends to coerce subjects to make particular choices; furthermore, those charged with reviewing requests to use artificial hearts have faced serious moral challenges. There has been a great deal of pressure associated with the race to be the first medical center to use a mechanical heart or to be the first to use one successfully. Considerable financial and publicity stakes are involved for the researcher, the institution, and any companies in which the institution or researcher might have an interest. Local IRBs usually do not have the requisite expertise or independence to evaluate exactly what sorts of criteria to use to govern subject selection, consent forms, or the methods for accumulating data on subjects over long periods of time. Because of limited time and resources, local IRBs often do not adequately monitor clinical trials over time, which provides little protection for research subjects.
Once it became clear in the 1980s that the devices then available could not safely support long-term heart function in human beings, enthusiasm for artificial hearts turned to their temporary use. Here, too, tough ethical questions must be confronted. If artificial hearts are to be used on a temporary basis, is it permissible to implant them without the explicit consent of a person who has undergone a sudden, unexpected heart failure? Which patients would constitute the best patient population for testing devices intended for temporary use only: those nearest death and thought to have the lowest risk for the greatest potential benefit, or those not quite as sick, who are most likely to recover if given a respite by an LVAD or temporary use of an artificial heart? It is not clear that those who are given artificial hearts or LVADs on a temporary basis understand what their rights are to turn off these devices. Nor is it clear, according to George Annas, that the use of these devices will contribute to an overall increase in the number of lives saved. When cadaver hearts are scarce, the use of artificial hearts or bridge devices as a prelude to transplant means only that the identity of those getting a chance at a transplant may change while the overall number of transplants done remains the same (Caplan). Many believe that assist devices will not save more lives since there are only a small number of cadaver hearts available for transplant. One must find the balance between simply extending life versus improving its quality and happiness.
The Societal Impact of the Artificial Heart
One of the obvious moral questions raised by research to develop an artificial heart is whether developing this device is the best way to spend limited research dollars in meeting the healthcare needs of Americans or of the world's population as a whole. Artificial heart research is expensive. The costs of doing the first TAH implants ran into the hundreds of thousands of dollars, and current research promises to be much more costly. Approximately 40,000 people die annually from heart disease so the life saving potential of the artificial heart appears significant, yet the development of expensive new medical technology raises ethical questions about where money should be allocated and what diseases should be the priority for research.
Many experts note that to develop, test, and manufacture a fully perfected artificial heart would probably cost billions of dollars. Those most likely to benefit from access to such a device would likely be those who could afford insurance to pay for mechanical hearts. The quest for a totally implantable artificial heart, as with many other new procedures, devices, and pharmaceuticals, brings to mind questions of equity and justice in asking all to bear the cost of research for a device that would only be available to some. Questions of fairness also exist in the decision to build a machine that may add years of life to those at the end of their life span, when tens of millions of persons around the globe die before reaching adolescence from diseases and injuries that can be prevented. Explicit debates about fairness have not been very much in evidence regarding how best to allocate resources to perfect new therapies in American healthcare policy. If the pursuit of a TAH is to continue, it would seem prudent to make considerations of fairness a more central part of the policy debate.
Finally, the development of the total artificial heart and the use of ventricular assist devices have gained popularity and are believed to be one solution to the problem of a limited number of donor hearts and an ever-increasing transplant waiting list. It is imperative as we seek new technology to replace organs that cease to function effectively that we continually ask, what are the acceptable limits of our drive for prolonging life through radical replacement technologies?
arthur l. caplan (1995)
revised by arthur l. caplan
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