stanford medicine


The first successful adult heart transplant performed in the United States, captured in the last frame of a surgical resident’s film. Among those pictured are nurse Bernadine Hartman and Drs. Norman Shumway, Edward Stinson and Denver Nelson.

What Have We Done?

Forty years of heart transplants

Tony Huesman’s doctor back in Ohio thought the idea was outrageous, and even the front-desk clerks at Stanford Hospital laughed in disbelief when the 20-year-old said he had come more than 2,000 miles to get a new heart. But the real affront came when Huesman, all gowned and prepped for his big transplant surgery, had a priest show up in his hospital room to give him his last rites.

Sure, he had a bum heart, and this was 1978, when the field of heart transplantation was so new that most considered the procedure “off the wall,” Huesman says. But he was young and strong and determined to live.

“I said, ‘No, no, I’m not going to die — I’m going to make it through this,’” Huesman recalls from his home in Dayton, Ohio. “I said, ‘Pray for me all you want, but don’t give me that one.’”

Now 51, Huesman has lived for 30 years with the same heart he got that day at Stanford — a worldwide record. He was patient No. 153 in the Stanford heart transplant program, which this year celebrates the 40th anniversary of its landmark procedure: the first successful human heart transplant in the United States.

Heart transplantation has come a long way since that time, when patients’ lives were measured in days, not years, and the very idea of putting a stranger’s heart into the body of another was out of this world.

Gone are the times when the threat of organ rejection led doctors to drastically suppress patients’ immune systems, which meant many died of terrible infections or spent months in bubble-like intensive care rooms, suffering psychoses from prolonged isolation. Today, patients often head home from the hospital in just a week. To date, some 44,000 people in the United States, and more than 70,000 worldwide, have undergone the procedure.

What has made it possible are developments on a variety of fronts, many emanating from Stanford. These include new anti-rejection drugs, new techniques for predicting organ rejection and new ways to care for patients after their transplants. Legal changes also have paved the way for the procedure to become almost (but not quite) ordinary. Now, laws encourage organ donation and define death based on brain function, rather than heart function, so that beating hearts can be extracted from brain-dead patients.

“We do essentially the same surgery today as we did” early on, says Sharon Hunt, MD, a professor of cardiovascular medicine who, after 35 years of experience, jokingly calls herself the longest-living transplant cardiologist. “What is different is the way we treat the patients afterward — the immunosuppression and how we treat the complications.”

In the future, patients might be freed completely from these oppressive drugs, once doctors achieve the ultimate goal of transplantation science, something known as immune tolerance. This is an elusive biological state in which the body is tricked into thinking a stranger’s organ is its own. “I think it will happen as we learn how genes control rejection. That will lead to some kind of treatment, I believe, hopefully in our life,” says Bruce Reitz, MD, the Norman E. Shumway Professor of Cardiothoracic Surgery.

The future might also bring a wireless version of the mechanical pump, one as small as a C-battery, which could be easily implanted as a permanent prop for an ailing heart. “You’d get your pump and go home the same day,” says Robert Robbins, MD, professor and chair of cardiothoracic surgery. “It sounds far-fetched, but it could happen.”

First times

Stanford’s stature as one of the country’s leading heart transplant centers was assured by the late Norman Shumway, MD, who carried out the first successful procedure in the United States, in 1968. After nine years of painstaking research in dogs, Shumway declared in 1967 in the Journal of the American Medical Association that he was ready to do a trial in humans. A month later, on the evening of Jan. 7, he carved open the chest of a critically ill steelworker, 54-year-old Mike Kasperak of East Palo Alto, and removed his diseased heart.

“Basically, I sort of asked him,‘Are you sure this is legal?’”

It was an awe-inspiring moment as he and his colleagues prepared to sew in an organ taken from the body of a Sunnyvale, Calif., woman, who had died of a massive brain hemorrhage and whose body was transported to an adjacent operating room.

“Shumway usually maintained a light atmosphere in the operating room, but on that particular occasion, it was pretty solemn,” recalls Edward Stinson, MD, professor emeritus of cardiothoracic surgery. “We reached the first milestone when we removed the recipient’s heart. He (Shumway) and I both looked down into this empty pericardial cavity with the heart gone, and the patient was on bypass. We looked at one another and said, ‘What on earth have we done?’ Basically, I sort of asked him, ‘Are you sure this is legal?’ He said, ‘I think so.’

“Once we had implanted the donor heart, and it started to beat, there was a surge of relief,” Stinson says. “At that point, we knew it was going to work from a technical standpoint, so the rest of the case was more routine. There was just general buzz as the donor heart was resuscitated. It was a palpable aura of relief and excitement….As is commonly said, it was awesome.”

The procedure took place amid a media frenzy, as Shumway, following a news leak of the historic operation, reluctantly appeared the next morning before 150 reporters at a press conference in a School of Medicine classroom.

“It was much like having the Beatles in town,” recalls longtime transplant coordinator Joan Miller, RN. “Reporters were crawling up the side of the building to peek in the window and get pictures. It was just great fun and exciting.”

The publicity ignited near-hysteria in international circles, and nearly 100 medical centers jumped in to try the new procedure.

“It was a sexy thing to do if you thought you were a major cardiac center, but most of the patients died horrible deaths,” cardiovascular medicine professor Hunt recalls.

Most patients succumbed to massive infections and malignancies — fungus, herpes, bacterial infections and lymphomas — as the crude anti-rejection drugs of the day destroyed their bodies’ ability to fend off disease.

Heart transplantation then “was a dramatic way to save a desperate situation, but the procedure had so many complications of its own,” says Reitz, who began his career in Shumway’s lab in 1969.

As patient outcomes proved dismal, with fewer than 20 percent living a year, physicians called for a national moratorium on heart transplantation. But Shumway persisted, persuaded by his years of research that it was a viable procedure that could return patients to productive lives.

Honing alone

During the dark ’70s, Stanford largely stood alone as the only center performing the procedure as Shumway and his colleagues continued refining the process. Shumway was even threatened with murder charges by the Santa Clara County coroner for removing beating hearts from brain-dead shooting victims. Shumway also was called to testify in a murder trial in Oakland, Calif., after the shooting victim’s heart was removed for transplantation into a Stanford patient.

“The main difficulty was in trying to convince the neurological community about the validity of the concept of brain death and to try to identify appropriate donors,” Stinson recalls. “That was a fight.”

The issue ultimately would be resolved by the 1974 approval of a California law on brain death, allowing doctors to remove a beating heart from the body of a brain-dead patient.

Though the legal issues were resolved, the experience was still grueling for patients like Huesman, who would be confined to the intensive care unit for months at a time while they were subjected to massive immune suppression that made them vulnerable to infection. Huesman, a high school athlete who suffered from familial cardiomyopathy (a weakening of the heart muscle), recalls being isolated behind double glass doors in the north ICU, attended by a nurse whose job included scrubbing down the room three times a day. Though he didn’t develop the ICU psychosis of some patients, who experienced fits of crying and depression, he did suffer from chronic boredom during his three-month hospital stay and would sometimes pick up a mop and clean the floor himself.

When he made a foray out of his room, he covered up from head to toe with gown, mask, booties, gloves and hat — a curious sight in the hospital corridors.

“Patients couldn’t help but feel freakish, and people would look at them all wrapped up like that and think, are they contagious?” recalls transplant social worker Mary Burge. “People didn’t realize it was for the patients’ protection.”

“It was a shotgun approach — Kill all the T cells.”

Experience would prove those precautions to be unnecessary in preventing infection, Hunt says. “It turns out it made no difference. So a lot of money was wasted on that,” she says.

What would really make the difference for patient survival were improvements in drugs to prevent rejection. The early medications were primitive indeed.

“It was a shotgun approach — kill all the T cells,” Robbins says of those early formulations. Newer drugs, including medications like mycophenolate, would be more selective, targeting those cells specifically involved in organ rejection, he says.

Huesman recalls taking one particularly nasty drug called ATG (anti-thymocyte globulin), which was injected twice a day in the arm or leg. The drug, a formulation of rabbit-derived antibodies that target human T cells, was made in the early days by a senior research associate at Stanford. Patients responded violently to the painful injections, often developing tennis ball-sized lumps in their arms or legs. “I swear, I still have some remnants in my arm, up in my biceps,” Huesman says. The drug, now commercially manufactured in more refined form, is still used, though it is given to patients intravenously, rather than being injected into the muscle, causing minimal side effects.

The advent of cyclosporine, an immunosuppressive drug developed in Europe, dramatically changed the landscape. The drug was studied at Stanford in the late ’70s, and first used for heart transplantation in December 1980. It also paved the way for successful lung transplants. The clinical use of cyclosporine got its start after an Arizona newspaper executive, Mary Gohlke, contacted Stanford seeking to be the first combined heart-lung transplant. Gohlke was desperate for a new heart and lungs, as hers were rapidly failing due to primary pulmonary hypertension. Stanford was waiting for cyclosporine approval before it would do the transplant, but Gohlke was in no position to wait. She contacted her U.S. senator, who put pressure on the Food and Drug Administration to approve the drug in a one-day turnaround. Gohlke got her historic transplant in March 1981 — and five more years of life.

Cyclosporine “definitely changed the field — brought it from a very labor-intensive treatment with lots of complications to a treatment that, while still difficult, was significantly better,” says Reitz, who performed Gohlke’s landmark surgery.

After cyclosporine was introduced, first-year survival rates among transplant recipients jumped from 66 percent to more than 80 percent, Reitz says. It led to wider acceptance of the procedure, with an exponential increase in the number of heart transplants performed nationwide.

Another major advance in the field came in the mid-1970s with the development of a biopsy to detect when a patient was in the throes of rejecting an implanted heart. Before the biopsy came to fore, doctors used “seat-of-the-pants” methods to detect rejection, listening to the heart or just observing that a patient wasn’t looking particularly well, Hunt says. With the biopsy, developed at Stanford by visiting scientist Philip Caves, MB, FRCS, clinicians could snip off a 1-millimeter fragment of the heart through a catheter fed into a neck vein. By looking at the tiny piece of tissue through a microscope, doctors could see the number of lymphocytes — white blood cells — collecting in the muscle fibers, a signal of rejection.

“It was so important to detect rejection before it became a clinical problem,” Reitz says of the biopsy procedure, which is routinely performed in patients today.

In the early 1970s, Stanford also pioneered methods for preserving organs, avoiding the logistical and emotional nightmare of having to transport cadavers to a hospital where recipients were anxiously in wait.

“When I was a resident, we used to go out and we’d have to bring a deceased person’s body back, still on a ventilator,” Reitz recalls. “Then after the procedure, the remains would go back to the family for burial.”

Scientists developed techniques to preserve a heart in a high-potassium electrolyte solution and then pack it on ice, keeping it viable for six or seven hours.

“It comes in feeling almost frozen,” Reitz says. “As soon as it gets warm blood in it, it starts quivering and beating. It’s neat. Even after all these years, it’s still exciting to see.”

With new methods for preservation, Stanford did not have to look to California alone for donors but could use organs from as far as 1,000 miles away.

Nonetheless, a scarcity of donors remains an obstacle to heart transplantation today. While tens of thousands of patients wait, only about 2,000 donor organs become available each year, most of them from victims of motor vehicle accidents, Robbins says.

Stanford has benefited from being in an area where the donor procurement agency, known as the California Transplant Donor Network, is actively involved in promoting donation. The medical center’s patients now wait an average of six weeks for hearts, compared with the national average of three to four months, Reitz says.

Stanford remains one of the most prolific centers in the country, performing about 60 heart procedures a year. Since Shumway’s first procedure in 1968, the medical center has implanted 1,483 hearts in 1,390 patients as of Sept. 1, 2008, some of whom have been transplanted twice. More than 86 percent of patients transplanted at Stanford now live three years or longer, compared with 80 percent nationwide.

“We’re pushing the envelope, doing patients we would never have done 10 years ago — patients who are older and sicker,” Robbins says. “And despite that, we’re getting outstanding results.”

These results are due largely to Stanford’s long experience and its multidisciplinary, team approach to patient care, which was Shumway’s model, says Robbins. Many of the early members of the transplant team, including the nurses, social workers and physicians, continue to work at Stanford, always seeking to refine the practice.

“There is this great continuity — people have been here a long time, and they don’t make the same mistakes over and over again,” says Miller, the transplant coordinator, who retired in August after 45 years at Stanford.

As the technique grew more refined, the costs of the procedure grew exponentially — from roughly $60,000 in the 1970s to an average charge of $748,000 per patient today at Stanford. Early on, Shumway and his colleagues donated their time, while a few private insurers agreed to cover the costs of care. Medicare initially paid for some of the ancillary costs as well, but in 1979, it threatened to withdraw its coverage, claiming the procedure was still experimental. Stanford officials, saying the move put the program in jeopardy, lobbied the federal government, which ultimately agreed to cover the procedure in full. Other private insurers soon followed suit.

Certainly no one predicted at that time that patients like Huesman would live so long. In fact, in the early days, no one knew how to counsel patients on what to expect from their lives.

“I had a patient from Arizona, and he was joking, ‘I’m really annoyed with you guys — because I’m still alive. I never saved for my retirement. I never made any plans. I never thought I’d live to be this old,’” Miller says, adding. “We’re much better now at life counseling for patients.”

Huesman says when he returned to Ohio from Stanford, he figured he’d have only five years more to live, because that was the record in those days.

“So I never made long-term plans. Getting married and having children, that wasn’t going to happen,” he says, though he finally relented and got married 11 years ago.

He also started Huesman Heart Foundation, which aims to prevent heart disease through children’s education, and has written several children’s books, winning humanitarian awards for his work. He’s less energetic now and has developed diabetes, skin cancers and osteoporosis, among other conditions stemming from long-term treatment with steroids and other anti-rejection medications. But he still works three days a week at his longtime job at a sporting goods store.

“So here I am 30 years later. Go figure. There’s a reason — I don’t know what it is, but obviously I feel very blessed to have this second chance.”

extras headline
movie poster frame

And the beat
goes on

Future cures for ailing hearts

While there have been enormous strides in heart transplantation in the last four decades, the future of the procedure remains limited by a perennial shortage of donor organs, complications associated with the operation and chronic rejection issues.

Part of the solution might be mechanical heart pumps, which can be used to prop up an ailing heart muscle, says Robert Robbins, MD, professor and chair of cardiothoracic surgery. Stanford developed the earliest pump, called a left-ventricular assist device, which was implanted in the first patient in 1984. It was a cumbersome machine with a four-pound battery pack, and was designed to be temporary, keeping patients alive until an organ became available for transplant.

Since then, scientists have invented a series of smaller, easier to implant pumps, some with the goal of serving as a permanent support for the heart. Robbins envisions the day when these pumps will be powered with wireless technology and durable enough that the only maintenance required would be a battery change every five years. The pump wouldn’t entirely replace transplantation but it would be a very good alternative, he says. Such a system will take decades to develop, he adds.

Bruce Reitz, MD, the Norman E. Shumway Professor of Cardiothoracic Surgery, says he is not quite as bullish on pumps, but rather is looking to human biology for answers. One of the ultimate goals is to free patients of immune-suppressing drugs by coaxing the body into a state of immune tolerance so it accepts the organ as part of itself. So far, it’s proven to be very difficult to trick the body in this fashion, though there has been some limited success in kidney and liver transplantation.

Scientists also are looking to stem cells as a possible method for mending ailing hearts. They are trying to entice embryonic stem cells into becoming heart cells capable of replacing damaged heart tissue. But success so far has been elusive.

“Embryonic stem cells have great promise, but I think we’re several years away from magically putting stem cells into a failing heart to treat it,” Robbins says.

Change of hearts

One man, two transplants

When Danilo Oncena’s doctors first broached the idea of a heart transplant, his reaction was predictable enough, given that it was 1978 and fewer than 100 patients in the United States were still alive after the experience.

“I told them, ‘You’re crazy,’ ” he laughs. He cast his mind back to the earliest transplant patients, who had lived only a few weeks. “I said, ‘That was successful?’” With time, however, the Pittsburg, Calif., resident reconsidered; cardiomyopathy was steadily draining the strength from his heart. His doctor referred him to Stanford, then virtually the only medical center in the country doing heart transplants, where he was introduced to a patient who had undergone the procedure only a few days before. Oncena was impressed by the man’s robust look and enthusiasm.

“I said, ‘I want one, too,’” he recalls.

It would not be that easy. Oncena, then 35, would have to wait nine months to get his new heart. In the 1970s, transplantation barely made an impression in the public consciousness and donors were exceedingly scarce. By the time a suitable organ became available, he was very frail, a skeletal 100 pounds. “I felt I had about a week left,” he says.

He reflects on that time from the living room of his modest, single-story home, where he’s lived some 40 years. He slowly shuffles to the door, a slender, soft-spoken man. As two of his young grandchildren bound through the house, his wife, Violet, shows off the albums she’s lovingly created with photos, news clippings and other paraphernalia documenting Oncena’s lengthy medical experience.

After his 1979 transplant, Oncena spent 70 days in the hospital, much of it in isolation in the intensive care unit, as anti-rejection drugs had virtually wiped out his immune system. The photos show him in a hospital wheelchair, a wisp of a figure barely recognizable under a gown and cap, with his wife and five young children at his side.

“There was a lot of pain and hardship because the medications had a lot of side effects,” he says. Among other complications, he developed a case of chicken pox.

But his new heart proved to be a sturdy stand-in, serving him well for 26 years. At that point, he was 62 and had already outlived many of his counterparts, becoming one of Stanford’s longest-lived patients.

“I know some patients who were done before me, and some who came after me, and they’re all gone now,” he says wistfully.

By 2005, his heart began to give way to the body’s penchant for rejection. That year, Oncena returned to Stanford, his second home, he calls it, for a fresh organ. This time the experience was altogether different, he says.

“This time around, it was a lot better — the information available, the equipment, the skills of the doctors and nurses, the technology,” says Oncena, an engineer.

This time, he was in the intensive care unit just one night before he started asking the nurses for something to drink — a Snapple, maybe, or a nice cup of hot tea with lemon.

His wife arrived the morning after to find him without his breathing tube, propped up in a chair. “I was so surprised,” she says. “He was up and ready to eat his breakfast the next day. I couldn’t accept that he was getting out of the ICU.”

Unlike the old days of isolation, he was able to walk freely around the unit. He was out of the hospital in just six days and soon returned work.

Oncena, now 66, retired last year from his job in the medical equipment unit of Siemens, the German-based electrical-equipment manufacturer, where he spent most of his career. He says he doesn’t think much about his transplant. “They tell you to live life as normal as possible. That’s what I’m doing,” he says, but he adds, “Every day is a bonus.”

He spends much of his time now with his children and four grandchildren, who live nearby. “It’s a gift for him to be able to see his children grow up,” says his wife. “And now he’s lucky to see his grandchildren, too.”

Stanford will celebrate 40 years of heart transplantation on Oct. 24

The all-day event will be held at the Arrillaga Alumni Center on campus. The celebration will include a morning symposium on state-of-the-art science in transplantation, and an afternoon reunion of transplant recipients from around the country. For more information, visit the Cardiovascular Institute site.





©2008 Stanford University  |  Terms of Use  |  About Us