Cardiac Surgeons Seeking Replacements for Failing Hearts by Gina Shaw In 1965, when he was a medical student studying the artificial heart under cardiac pioneer Dr. Michael E. DeBakey, Dr. O.H. ìBudî Frazier heard an exciting prediction from DeBakeyís chief researcher. ìHe told me, ëBy 1980, there will be 100,000 Americans going back to useful, productive lives with artificial hearts,íî recalled Frazier, who as chief of cardiopulmonary transplantation at the Texas Heart Institute in Houston has performed more heart transplants than anyone else in the world. ìHe himself died of heart failure about five years ago, and of course, the problem turned out to be a lot more complex than it looked.î Heart transplantation, artificial hearts and other technologies to replace or assist a failing heart have had tantalizing successesóand heartbreaking failuresóin the past 40 years since Dr. Christiaan Barnard performed the first human heart transplant in South Africa in 1967. The recipient, a 55-year-old man dying of heart damage, survived 18 days with the heart of a 25-year-old woman who had died after a car accident beating in his chest. Since then, weíve seen the first artificial heart transplant in 1982 and the first successful pediatri c heart transplant in 1984. That young boy, James P. Lovette, then age 4, is today about to graduate from Case Western University with a masterís degree in bioethics and hopes someday to practice medicine at Columbia University Medical Center, the hospital where he received his groundbreaking surgery. But for every heartwarming success story such as Lovetteís, there are cases such as the first infant to receive a heart transplant, who was a patient of Frazierís. ìShe was 8 months old when we did her surgery in 1984,î he recalled. ìShe was a really sweet child, enjoying school, doing cheerleading. And then she just suddenly died at the age of 13 because her arteries occluded.î Thatís one of the primary challenges involved in heart transplantation, Frazier said. ìPatients develop, invariably, what we call accelerated atherosclerosis, which probably has something to do with injury to the endothelium of the arteries,î he explained. Surprisingly, he said, the population of patients who do best after a heart transplant is men in their 60s. ìThey tend to reject less, and if the surgery itself is successful, they usually live another 10 years or so, about the normal ëthreescore and 10.í But if you do a transplant on a 20-year-old, statistically he wonít live to see 30 unless you transplant him again.î The other major challenge: a lack of donors. About 1,000 heart patients die every year in the United States when their hearts give out before a transplant becomes available. ìOver the past five years, the number of heart transplants in this country hasnít changed significantly. Donor heart availability is the primary reason,î said Yoshifumi Naka, director of Cardiac Transplantation and Mechanical Circulatory Support Programs at Columbia University Medical Center. ìAt Columbia, we have more than 200 patients on our waiting list and are able to perform about 80 transplants a year. Nationally, the picture is about the same: There are about 6,000 people on the waiting list and around 2,000 transplants a year. The fundamental problem is a donor shortage, and I donít think that we can resolve this problem.î Giving the Heart a Boost Thatís why leading cardiac specialists such as Frazier and Naka are focusing much of their attention on the future of transplantation alternatives such as artificial hearts and assist devices such as the left ventricular assist device (LVAD). The first LVAD approved by the Food and Drug Administration, the HeartMate, manufactured by Thoratec Corp., is a fist-size implantable pump placed just below the diaphragm in the abdomen. There itís attached to the patientís own heart and collects blood from the left ventricle, pumping it through the aorta. The FDA initially approved the HeartMate in 1998 as a short-term therapyówhatís called ìbridge to transplantîófor patients awaiting heart transplantation who would not otherwise survive until a transplant became available. In fact, it turned out that the LVADs were so successful in supporting a patientís own heart and improving survival and quality of life that in 2002, the FDA also approved the device as a ìdestination therapyîóin other words, a permanent implant in patients who may never have a heart transplant. ìThe average survival rate after an LVAD implant is about 75 percent, and for someone whoís going to be dead, thatís very good,î said Frazier, who helped pioneer the HeartMate at the Texas Heart Institute and performed the first 26 LVAD implants. ìIt became apparent to me that once we had given these patients their implants, they did much better. The University of Michigan reported that 90 percent of their LVAD patients, who had been near death, lived at least a year, and I think Columbia has similar results. The last I looked, there were something like 56 patients whoíd been on these pumps more than three years. Thatís going to be the therapy of the future I think.î The next generation of LVADs includes the Jarvik 2000 (a valveless, electrically powered miniature flow pump that fits directly into the left ventricle), the HeartMate II (longer lasting and considerably lighter than its predecessor) and MicroMedís DeBakey VAD, which is now being tested in two trials, one a bridge-to-transplant trial and the other a destination-therapy trial. All of these are much smaller than the original HeartMate, allowing them to be implanted into smaller patients and permitting less invasive surgery. The DeBakey has the added advantage of having only one moving part, making it far less complicated than the original HeartMate. In June 2000, Frazier, who developed the Jarvik in collaboration with Dr. Robert Jarvik, the creator of the first artificial heart, traveled to Oxford, England, to implant the first Jarvik 2000 in a 63-year-old palliative care counselor, Peter Houghton, who was then near death from heart failure. A year later, Houghton completed a 91-mile charity walk in celebration of his first anniversary with the pump. Heís now the longest-surviving patient with a cardiac-assist device, having lived four and a half years since the initial implantation, during which time he has published two books, lectured widely, hiked in the Swiss Alps and the American West, flown in an ultra-light aircraft, and traveled extensively around the world. ìPrior to the surgery, heíd been in the hospital nine times over the previous six months. And after we implanted the pump, he hasnít been in the hospital since,î said Frazier. ìIn fact, we couldnít find him a couple of years ago for a celebration because he was hiking in the Alps. Itís a beautiful pump, and weíve never had one fail yet.î Indeed, the primary problem for the assist devices, said Frazier, is not one of technology but one of regulation. ìThe FDA has only approved these devices for patients who are damn near dead and on the transplant list,î he said. ìI have a lot of patients who meet one criterionótheyíre on the transplant listóbut theyíre not near death yet. Theyíd be ideal candidates for the Jarvik as a destination therapy, but itís not approved for them.î Frazier described one such patient, a young woman with severe heart failure whom he first saw five years ago and who is still working. ìHer heartís ejection fraction is about 15 percent; normally, it should be about 65 percent,î he said. The ejection fraction is the amount of blood your heartís left ventricle pumps out per beat. Some blood always stays in the chamber, so no one has an ejection fraction of 90 percent or 100 percent. ìShe gets up at 8 a.m., takes two hours to get ready, goes to work, works for an hour, then eats lunch and has to rest for an hour after eating lunch. Then she can work for another couple of hours before going home and going to bed to rest for the next day. If she came in nearly dead, we could put a pump in, but often when a patient suddenly deteriorates, we donít have time. Now is the ideal time to give her a pump, while sheís still healthy enough to survive the operation with a very good prognosis.î On the very near horizon, said Columbiaís Naka, is the third-generation LVAD: a still smaller flow pump, with the added plus of having no mechanical bearings. ìMechanical bearings can wear out and potentially fail,î said Naka. ìThe third-generation pumps have magnetic levitation bearings, meaning thereís no metal-to-metal contact and should last more than 10 years.î Two or three of these pumps have been placed in Europe and Australia, he noted, and a trial may come to the United States this year. The Bionic Heart? What about replacing the heart completely? Thatís another option that is showing promise as an alternative to donor-heart transplantation. The most famous and first completely self-contained artificial heart, the AbioCor Replacement Heart, was first implanted in a man named Robert Tools in June 2001. Tools survived 151 days with the AbioCor, about five times longer than the one-month lifespan he was given by doctors without the replacement heart. (Like the other patients who have had the still-experimental surgery, Tools had exhausted existing therapies for his end-stage heart failure and was unable to receive a donor heart.) ìAbout 16 or 17 of these devices have been placed to date,î said Naka. ìThe biggest problem is the criteria for enrollment in the trial: You have to be the very sickest of the sickest, within a month of death. That means that not only is your heart very sick, but your kidney and liver functions are abnormal as well. These patients die most often from comorbid conditions. Device failure, while it happens, is not frequent.î ABIOMED, the deviceís manufacturer, has applied to the FDA for commercial approval under a Humanitarian Device Exemption, which would make the AbioCor available to up to 4,000 patients with end-stage heart failure each year. The AbioCor has another limitation: its size. Currently, itís about one-third larger than a normal heart, said Frazier, its developer. ìYou can only fit it in about 40 percent of the adult population,î he explained. Recently, however, the successful treatment of a young man with heart failure using the HeartMate II pump has inspired him to begin work on a modification to the AbioCor. In November, Everardo Flores became the first patient to be supported by the HeartMate II for a full year. In October 2003, he was admitted to the hospital with severe cardiomyopathy and implanted with the device to await a transplant. ìHe wouldnít have lived a month without itóin fact, I donít think he would have lived a week,î said Frazier. Because he was so small, no conventional pump would work for him, but the smaller HeartMate II did. A year later, heís back at work as a mechanic and expecting his second child. But there was something else unique about Flores that intrigued Frazier. ìI never felt a pulse in him, and I hadnít seen that before,î he said. ìIt led me to think again about the total artificial heart. If you could make a continuous flow heartócompletely pulselessóyou could make it half the size of a normal heart and it would still do the same amount of work.î Since September 2004, Frazier has done three animal experiments with an experimental second-generation total replacement heartóright now, a hybrid of two small Jarvik pumps. The possibilities look promising, he said. ìIf we can make a total artificial heart thatís completely pulseless, we can reduce the cost and the size of the pump, and power it totally from the inside so that there will be nothing coming out of the bodyóno wires, nothing. We could finally have a total heart that would work long term and fit in everyone.î How soon might that be? ìWe doctors try not to be excited,î Frazier cautioned. ìBut weíre making headway. Even over the last year, thereís been logarithmic progress in the field. Iím not going to make a firm prediction, but I suspect that in a decade, weíll be able to expand this technology to give meaningful lives and avoid premature death in a lot of these tragic cases.î Gina Shaw is the medical writer for The Washington Diplomat.