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Physicians Update

 
Summer 2005: Transplantation

Novel Heart Transplants Target High-risk Patients

06/01/2005

UCLA heart transplant physicians, who perform an average of 100 transplants per year, have developed innovative ways to save the lives of patients with end-stage heart failure who otherwise may die while waiting for a donated organ because they are considered too old or sick.

Alternate Hearts

Alternate, or nonstandard, donor hearts are increasingly used at UCLA for higher risk recipients and critically ill patients with end-stage heart failure. “These patients would be turned downin many other transplant programs because of their age or multiple risk factors,” explains Hillel Laks, M.D., head of UCLA’s Heart Transplant Program. Currently, 13 percent of people on the waiting list for donated hearts are over age 65. “By using a marginal heart that would not be appropriate for someone on the regular transplant list, we have been able to expand the number of patients who can get a transplant.”

UCLA’s program was the first to propose the alternate list concept. Over the past 13 years, close to 90 alternate heart transplants have been performed at UCLA on high-risk candidate—those who are over 65 or su¤er from another condition such as kidney trouble, diabetes with complications, or cancer in remission. The types of hearts used have expanded to include borderlinefunctioning hearts that surgeons operate on before transplanting—coronary disease that can be bypassed, holes in hearts that can be closed, and leaking valves that can be repaired.

Preservation of a borderline heart is crucial so that deterioration of function remains minimal. “By removing the white blood cells and controlling reperfusion when blood first enters the organ, we achieve better function of the heart compared to many centers that use standard techniques. Reperfusion also allows us to accept hearts outside our local area,” Dr. Laks notes.

UCLA uses ingenuity matching donor hearts to recipients. “For example, an older donor with a hypertrophied heart due to high blood pressure involves a higher risk for the recipient. If a long transport time is avoided and you use the heart on someone much smaller than the donor—anelderly female, for example—then those hearts will work very well,” Dr. Laks says. “We might accept a heart with deteriorating contractibility caused by brain death in a young person and use that heart in a smaller recipient who would require less pumping volume.”

Four years post-transplant, no statistical di¤erence exists between outcomes for marginal and standard hearts at UCLA. After five years, 59.5 percent of patients are still alive, compared with 76 percent of UCLA’s regular heart recipients. Nationally, 72.5 percent of patients are living five years after a heart transplant.

“The reason the survival decreases after five or six years with the alternate heart is that older people start to get other diseases. However, increasing the longevity by even five years in a functional person in their late 60s or 70s is extremely valuable, and many of them live much longer. Some of our older patients have lived 10 to 12 years with marginal hearts,” Dr. Laks says. UCLA’s oldest alternate heart recipient, now 83, received his transplant 13 years ago.

Ventricular Assist Devices

The future of ventricular assist devices is heading down three paths with UCLA on the front edge of all three: bridge to transplant, destination therapy and artificial heart,” says Mark Plunkett, M.D., director of UCLA’s pediatric heart transplant program.

These devices currently play a major role in keeping patients with end-stage heart disease refractory to medical therapy alive until a suitable donor becomes available as a bridge to transplant. At UCLA, approximately 25 devices are implanted each year. The devices sustain circulation by taking over up to two-thirds of theheart’s pumping, thus allowing some patients to leave the hospital and wait at home for a heart to become available for transplantation.

Because of the limited supply of heart donors, these mechanical pumps have begun to be used as destination therapy—a new concept used primarily for patients older than age 70 or for patients who are not candidates for transplantation. “The limiting factor right now is the durability of the mechanical pump that has been used,” Dr. Plunkett explains. This pulsatile pump is larger than a fist and usually is implanted in the abdomen with tubes connecting to the heart through the diaphragm.

The good news is that three newer, much smaller pumps are being tested in patients at UCLA. This new generation of thumb-size devices sits either inside or outside the heart. Known as axial flow pumps, they contain a little propeller (called an impellor) that pumps seven to 10 liters of blood per minute, but without pulsatility. “The issue of pulsatility is an interesting current topic of research. If we implant a pump that generates a lot of blood flow but no pulse, will the patient benefit? If that proves to be true, it would mean that the new devices we are using would work very e¤ectively.” Dr. Plunkett reflects. “Ultimately, all this is leading up to a perfected artificial heart.”

“These smaller pumps are much simpler and less likely to break down,” notes Jaime Moriguchi, M.D., medical director of UCLA’s Mechanical Circulatory Support Program. “More importantly, they can be placed in smaller men, women and children who currently are not candidates for the larger pulsatile pumps.

"The axial flow pumps are less traumatic to implant, Dr. Laks adds, since patients do not require the heartlung machine during surgery. UCLA is one of the few centers in the country approved to use assist devices for destination therapy.

“All of these pumps have a finite lifespan due to wear and tear,” Dr. Moriguchi notes. “By combining adjuvant heart failure therapies, such as cell transplant or muscle-building drugs like the asthma medication clenbuterol, it appears that heart muscle can significantly recover to the point where the pumps can actually be removed. It is quite possible that the most significant contribution of these mechanical pumps will be in their role as bridges to recovery so that these patients will never need a heart transplant.”

Reducing Rejection

As one of the largest heart transplant programs in the country, UCLA sees some of the most critically ill patients, yet the survival rates are impressive. One-year survival is 90 percent, and three year is 75 percent, both figures higher than the national average. A contributing factor to these statistics is the after-transplant care and control of rejection factors.

“We’ve changed our anti-rejection regimen over the past decade. In 1990, 40 percent of our patients would not experience biopsy-proven rejection; today that figure is 96 percent,” notes Jon Kobashigawa, M.D., medical director of UCLA’s Heart Transplant Program. His groundbreaking work with statins in the 1990s demonstrated that cholesterol-lowering drugs knocked out the natural killer cell activity in patients with heart transplants. Later studies proved that combining mycophenolate mofetil, tacrolimus and pravastatin significantly decreases rejection episodes. Beginning in 1986, UCLA went against common wisdom and began to wean post-transplant patients o¤ steroids after six months to avoid long-term complications of the drugs and showed that patients can do very well without steroids.

Newer drugs are also being used.Everolimus, a proliferation signal inhibitor, and its sister drug sirolimus help prevent cell growth. Sirolimus is also being used at UCLA to treat transplant coronary artery disease, a condition occurring more often as recipients live longer.

Innovative ways to identify rejection include a simple blood test that uses genomics to detect 12 genes that upregulate specifically when rejection is present. With this blood test, UCLA has decreased the number of heart biopsies needed to detect rejection in the first year. Heart biopsies are no longer performed after one year posttransplant.

New frontiers of rejection research include antibody-mediated rejection, which Michael Fishbein, M.D., at UCLA has championed. Cellular rejection can be detected through biopsy. However, antibodies are too small to be detected. Dr. Fishbein has developed C4D staining to detect this form of rejection. If rejection is identified, patients can be treated with high-dose corticosteroids.

Extracorporeal photopheresis is also used to treat antibody-mediated rejection and recurrent rejection. In this technique, white blood cells are removed, a compound is added and then treated with ultraviolet light to cause an irreversible bond with the white cells—signaling the suppression regulatory cells in the body to shut down the part of the immune system involved in the rejection process.

“We have it all here at UCLA—a tremendous cardiomyopathy program, world-class surgical physicians and outstanding post-transplant care that all work very well together,” Dr. Kobashigawa notes.





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