On this day in 2001, a petite 44-year-old woman received a successful heart transplant at Ronald Reagan UCLA Medical Center, thanks to an experimental Total Artificial Heart designed for smaller patients.
The UCLA patient was the first person in California to receive the smaller Total Artificial Heart, and the first patient in the world with the device to be bridged to a successful heart transplant — that is, to go from needing a transplant to receiving one.
The 50cc SynCardia temporary Total Artificial Heart is a smaller investigational version of the larger 70cc SynCardia heart, which was approved for use in people awaiting a transplant by the Federal Food and Drug Administration in 2004 and has been used by more than 1,440 patients worldwide.
The 50cc device is designed to be used by smaller patients — including most women, some men and many adolescents — with end-stage biventricular heart failure, where both sides of the heart are failing to pump enough blood to sustain the body. The device provides mechanical support until a donor heart can be found.
Nemah Kahala, a wife and mother of five, was transferred to UCLA from Kaiser Permanente Los Angeles Medical Center in March. She was suffering from restrictive heart muscle disease and in critical condition. Her heart failure was so advanced that repair surgery and other mechanical assist devices could not help.
Kahala was placed on a life support system called extra corporal membrane oxygenation, but this only works for about 10 days before a person’s organs begin to deteriorate.
With the clock ticking, doctors needed to buy time by replacing Kahala’s failing heart with an artificial heart while she waited for a heart transplant. Her chest cavity was too small for her to receive the larger 70cc artificial heart. However, under a one-time emergency use permitted under FDA guidelines, her doctors were able to implant the experimental 50cc device.
“Mrs. Kahala’s condition was deteriorating so rapidly that she would have not survived while waiting for a transplant,” said her surgeon, Dr. Abbas Ardehali, a professor of cardiothoracic surgery and director of the UCLA Heart and Lung Transplant Program. “We were grateful to have this experimental technology available to save her life and help bridge her to a donor heart.”
The artificial heart provides an immediate and safe flow of blood to help vital organs recover faster and make patients better transplant candidates.
After the two-hour surgery to implant the artificial heart, Kahala remained hospitalized in the intensive care unit and eventually began daily physical therapy to help make her stronger for transplant surgery.
Two weeks after the total artificial heart surgery, she was strong enough to be placed on the heart transplant list. After a week of waiting, a donor heart was found.
“In addition to the high-tech medicine that kept her alive, Mrs. Kahala and her family exemplified how a solid support system that includes loved ones and a compassionate medical team practicing what we at UCLA have termed ‘Relational Medicine’ plays an important role in surviving a medical crisis,” said Dr. Mario Deng, professor of medicine and medical director of the Advanced Heart Failure, Mechanical Support and Heart Transplant program at UCLA.
Kahala was discharged from UCLA on April 18.
Since 2012, the UCLA Heart Transplant Program has implanted eight 70cc SynCardia Total Artificial Hearts. UCLA also participated in the clinical study of a 13.5-pound Freedom portable driver — a backpack-sized device that powers the artificial heart, allowing the patient to leave the hospital — that received FDA approval on June 26, 2014.
The FDA cautions that in the United States, the 50cc SynCardia temporary Total Artificial Heart is an investigational device, limited by United States law to investigational use. The 50cc TAH is in an FDA-approved clinical study.
On the same day, a patient was implanted with the world’s first self-contained mechanical heart after a 7-hour operation, a hospital in Louisville, Kentucky. The procedure was the first major advance in the development of an artificial replacement heart in nearly two decades.
The device, created by Danvers, Massachusetts-based Abiomed Inc., replaces the lower chambers of a patient’s failing heart with a plastic-and-metal motorized hydraulic pump which weighs 2 pounds (1 kg) and is about the size of a grapefruit.
It was the first artificial heart to be free of wires connecting it to the outside.
“This is the first time this has ever been done,” said Kathy Keadle, a spokeswoman at Jewish Hospital where the procedure was performed by University of Louisville surgeons Laman Gray and
Neither Abiomed nor hospital officials would disclose the name, sex or gender of the patients, all of whom are seriously ill. The long-awaited surgery had been expected by June 30 but was delayed because the company had not completed patient screening.
Abiomed got U.S. Food and Drug Administration approval in February’s 2001 to test the device on as many as 15 patients, all of whom are too ill to be candidates for a heart transplant. Unlike existing devices, which serve as a temporary solution to extend a patient’s life until a patient can secure a donor heart, the AbioCor heart is designed to be a fully functioning replacement heart.
The trial involved severely ill patients with less than 30 days to live, said John Thero, vice president and chief financial officer of Abiomed.
“This is not a bridge to transplant. There is a scarcity of donor hearts available,” Thero said in a telephone interview. “We are starting with patients who are at the ends of their lives. They are not candidates for transplant and are near death. Our goal is to provide them with a reasonable quality of life and an extension of life.”
Thero said the current candidates had a life expectancy of two months. “While the device is designed to eventually go much longer, if we were able to double someone’s life expectancy, we would be very pleased,” he said.
The 40,000 patients awaiting heart transplants far outnumber the number of hearts available, and a successful mechanical heart could fill a huge need.
Earlier versions of the artificial heart were bulky and provided limited benefit to patients. In 1982, Dr. Barney Clark, 61, of Salt Lake City, Utah, received the first permanent artificial heart, known as Jarvik-7. He was bound to his bed by protruding cables, tubes and a noisy box-like air compressor during the 112 days that he survived with the artificial heart.
With the Jarvik-7 and other “bridge devices,” the outside connectors leave patients exposed to infection. The AbioCor contains a small electric motor attached to an implanted battery and is designed to last for years. Patients could wear a battery pack or plug into an electrical outlet to recharge the heart’s battery.
Long before human-to-human transplantation was ever imagined by the public, scientists were conducting pioneering medical and surgical research that would eventually lead to today’s transplantation successes. From the late 1700s until the early 1900s, the field of immunology was slowly evolving through the works of numerous independent scientists. Among the notable breakthroughs were Ehrlich’s discovery of antibodies and antigens, Lansteiner’s blood typing, and Metchnikoff’s theory of host resistance.
Because of advances in suturing techniques at the end of the 19th century, surgeons began to transplant organs in their lab research. At the start of the 20th century, enough experimentation had taken place to know that xenographic (cross species) transplants invariably failed, allogenic transplants (between individuals of same species) usually failed, while autografts (within the same individual, generally skin grafts) were almost always successful. It was also understood that repeat transplants between same donor and recipient experienced accelerated rejection, and that graft success was more likely when the donor and recipient shared a “blood relationship.”
Alexis Carrel was a French surgeon and Nobel laureate whose experiments involved sustaining life in animal organs outside the body. He received the 1912 Nobel Prize in Medicine or Physiology for his technique for suturing blood vessels. In the 1930s, he collaborated with the aviator Charles Lindbergh to invent a mechanical heart that circulated vital fluids through excised organs. Various organs and animal tissues were kept alive for many years in this fashion.
Throughout the 1940s and 50s, small but steady research advances were made. In 1958, Dickinson Richards, MD, chairman of the Columbia University Medical Division, and Andre Cournaud were awarded the same Nobel Prize for their work leading to fuller understanding of the physiology of the human heart using cardiac catheterization.
In that same year, Keith Reemtsma, MD, a member of the faculty of Tulane University who later became chairman of the Department of Surgery at Columbia University Medical Center, showed for the first time that immunosuppressive agents would prolong heart transplant survival in the laboratory setting.
At this time, Norman Shumway, MD, Richard Lower, MD, and their associates at Stanford University Medical Center were embarking on the development of heart-lung machines, solving perfusion issues, and pioneering surgical procedures to correct heart valve defects. Key to their success was experimentation with “topical hypothermia,” the localized hyper-cooling of the heart which allowed the interruption of blood flow and gave the surgeons the proper blood-free environment and adequate time to perform the repairs. Next came “autotransplantation,” where the heart would be excised and resutured in place.
By the mid-1960s, the Shumway group was convinced that immunologic rejection was the only remaining obstacle to successful clinical heart transplantation. In 1967, Michael DeBakey, MD, implanted an artificial left ventricle device of his design in a patient at Baylor College of Medicine in Houston.
In 1967, a human heart from one person was transplanted into the body of another by a South African surgeon named Dr. Christiaan Barnard in Cape Town. In early December, Dr. Barnard’s surgical team removed the heart of a 25-year-old woman who had died following an auto accident and placed it in the chest of Louis Washkansky, a 55-year-old man dying of heart damage. The patient survived for 18 days. Dr. Barnard had learned much of his technique from studying with the Stanford group. This first clinical heart transplantation experience stimulated world-wide notoriety, and many surgeons quickly co-opted the procedure. However, because many patients were dying soon after, the number of heart transplants dropped from 100 in 1968, to just 18 in 1970. It was recognized that the major problem was the body’s natural tendency to reject the new tissues.
Over the next 20 years, important advances in tissue typing and immunosuppressant drugs allowed more transplant operations to take place and increased patients’ survival rates. The most notable development in this area was Jean Borel’s discovery of cyclosporine, an immunosuppressant drug derived from soil fungus, in the mid 1970s.
The cardiac transplant program at Columbia University Medical Center began in 1971 as part of an investigational surgery program initiated by Dr. Keith Reemtsma. At that time, Columbia University Medical Center was one of only a handful of medical centers in the nation actively engaged in cardiac transplant research. Columbia University Medical Center’s first cardiac transplant was performed by Dr. Reemtsma in 1977, when survival rates had begun to improve significantly. That patient survived for 14 months. Two additional transplants were performed that year. Initially Columbia University Medical Center accepted patients deemed too risky for transplantation by Stanford and the Medical College of Virginia, the only other medical centers in the country performing heart transplants.
Thanks to the persistence of pioneers in immunosuppression research, transplant patients have dramatically expanded life expectancies. The first immunosuppressant drugs used in organ transplantation were the corticosteroids. In 1983, Columbia University Medical Center became one of a small group of medical centers to initiate clinical trials of cyclosporine; approved for commercial use in November of that year, it is still the most commonly prescribed immunosuppressant used in organ transplantation. General information on the variety of medications that may be prescribed for you is found in the chapter on Medications in the section Care and Concerns after Your Operation.
In 1984, the world’s first successful pediatric heart transplant was performed at Columbia on a four-year-old boy. He received a second transplant in 1989 and lived until he succumbed to other health issues in 2006.
Also, in 1984, in Loma Linda, California, Leonard Bailey, MD, implanted a baboon heart into a 12-day-old girl who came to be known as “Baby Fae.” The infant survived for twenty days as the most famous recipient of xenographic transplantation. Throughout the decade of the 1980s and into the 90s, physicians continue to refine techniques for balancing dosages of immunosuppressant medications to protect the new heart yet allow the patient sufficient immunologic function to stave off infection. In 1994 a new drug, tacrolimus or FK-506, originally discovered in a fungus sample, was approved for immunosuppression in transplant patients. Newer formulations of cyclosporine now enable efficacy (effectiveness) at lower, less toxic dosages.
While research on transplantation issues continues, other techniques for the management and cure of heart disease are also under development. Some future directions include:
Coronary assist devices and mechanical hearts are being developed or perfected to perform the functions of live tissues. Artificial hearts have been under development since the 1950s. In 1966, Dr. DeBakey first successfully implanted a booster pump as a temporary assist device. Columbia’s cardiac surgeons have been instrumental in the development of a LVAD (left ventricular assist device) to function as a bridge-to-transplantation for those waiting for a new heart to become available. Columbia University Medical Center’s lead role in the REMATCH clinical trial helped to lead to approval for the the LVAD as a permanent, or destination, therapy as well.
In 1969, Dr. Denton Cooley implanted the first completely artificial heart in a human, again on a temporary basis. The first permanent artificial heart, designed by Dr. Robert Jarvik, was implanted in 1982. Numbers of patients have received Jarvik or other artificial hearts since, but surviving recipients have tended to suffer strokes and related problems.
There is a tremendous gap in the number of patients waiting for new hearts and the number of organs that actually become available. In addition to avoiding the immunosuppression and rejection complications of transplantation, success in clinical application of such mechanical devices can help resolve the issue of organ availability and thus, stakes are high to continue research in this arena.
Advances in immunosuppression have most recently involved the development and expanded use of polyclonal and monoclonal antibodies to counteract steroid-resistant rejection. Research continues into the management, reversal and avoidance of accelerated atherosclerosis in the transplanted heart, believed to be caused or aggravated by the required suppression of the body’s normal immunology. From the development of more powerful and specific immunosuppressants to new treatments for accelerated graft atherosclerosis, advances in the science of immunology appear to hold the key to expanding the success of heart transplantation in our treatment of end-stage cardiac disease.
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Title: The Beat Goes On | Heart Transplants a Marvel of Modern Medicine