Discoveries Magazine

Cedars-Sinai

The Beat Goes On

A heart transplant can save patients like Jim Stavis from near-death and return them to a normal life. The next challenge: making a new heart last a lifetime.

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Hanging in Jim Stavis’ kitchen is a framed photo of the young football star who saved his life.

When the call finally came, Jim Stavis was scared but ready. It was November 2, 2005. Jim, then 50, was so weakened by his last dialysis treatment that he had checked himself into a hospital near his Calabasas, Calif., home. Both his heart and kidneys were failing, ravaged by decades of Type 1 diabetes.

Now, after a year on dialysis and four months on the waiting list for a new heart and kidney, the organs were on the way. The next thing he knew, the successful entrepreneur and father of three lay in the back of an ambulance, speeding toward Cedars-Sinai.

“I was pretty close to death,” Jim recalls. “I was tired of being sick, tired of being in this ‘will I live or won’t I?’ state. I wanted there to be a solution—or if not a solution, an end.”

After a 20-hour surgery, he woke up. A stranger’s heart was thumping loud and strong inside his chest, and a new kidney was already hard at work.

Jim had joined the ranks of the roughly 2,300 men and women who receive a lifesaving new heart each year in the United States. But this story of heart transplantation did not end there. The next challenge was just as critical: making the new heart last. It’s a challenge that medicine has faced since the beginnings of organ transplantation. After decades of steady progress, new research on the horizon has the potential to transform the field—and perhaps even make heart transplants a thing of the past.

It has been nearly half a century since the world’s first heart transplant made global headlines in 1967. The surgery, which took place at a hospital in South Africa, was a success—but the patient lived just 18 days, dying of double pneumonia.

“The immunosuppression wasn’t nearly as sophisticated then,” explains Sharon Hunt, MD, medical chief of the Heart Transplant Program at Stanford Hospital & Clinics and one of the early pioneers in post-transplant cardiology in the 1970s. “Most importantly, we couldn’t regulate it as well. Patients were dying either from infection because they were over-immunesuppressed or rejection because of the reverse.”

Today, post-transplant medicine is far more advanced. Thanks to better anti-rejection drugs, improved diagnostics, and superior surgical techniques, one-year survival rates have soared to a national average of 89 percent. At Cedars-Sinai, the rate is 91 percent.

After knocking on death’s door, patients often find themselves enjoying a quality of life they have not had in years. Two-thirds go back to work, and many have run marathons and scaled mountains. Median survival is 11 years; for those who survive the critical first year, it is 14.

But despite this tremendous progress, one issue remains: A transplanted heart still has a much shorter lifespan than the one you are born with. Ironically, one of the biggest problems is heart disease. Over time, patients’ coronary arteries can thicken— not because of hamburgers and French fries, but because their immune systems slowly and silently reject the organ.

Meanwhile, the same drugs that work wonders in extending survival can also lead to high blood pressure, kidney damage, and other health issues. And patients remain tethered to a lifetime of dependency on them.

“Anti-rejection medications are not the panacea we once thought they were,” says Jon Kobashigawa, MD, director of the Heart Transplant Program at Cedars-Sinai, which has performed more adult heart transplants than any other hospital in the United States for three consecutive years. “They revolutionized transplantation, but they can cause long-term problems, too, and those problems limit long-term survival. There’s still a lot of room for improvement.”

Three weeks after his transplant, Jim went home. The day he was discharged, a nurse came into his room with a bag of 26 medicines: anti-rejection drugs, blood pressure and cholesterol drugs, and supplements like magnesium and potassium.

“You think, my God, I’m going to need all this?” Jim remembers. “It was pretty intense. I realized the hardest part of the transplant was still ahead of me.”

The regimen is typical and can be pricey, easily costing patients $2,500 a month, depending on their insurance coverage. The medications also carry side effects, such as nausea and diarrhea, although Jim’s only problem was hair loss. Already balding due to age, he shrugged it off and shaved his head.

“Anti-rejection medications are not the panacea we once thought they were. They revolutionized transplantation, but they can cause long-term problems, too. … There’s still a lot of room for improvement.” –Jon Kobashigawa, MD

Anti-rejection drugs have always been a necessary evil in transplants. Without them, the immune system would quickly circle the wagons and ruthlessly run a newcomer heart right out of town, convinced it is a dangerous foreign invader.

Although the medicines act as an efficient “restraining order” on the immune system, their presence has drawbacks in addition to hypertension and kidney damage. Suppressing the immune system over many years can significantly raise patients’ risk for cancers, particularly skin cancers and lymphomas.

Additionally, many hearts eventually fail due to a low-grade, under-the-radar form of rejection called chronic rejection. Chronic rejection, which causes coronary disease in heart patients, is not well understood and remains a leading cause of death in long-term heart transplant patients. Although a second transplant is sometimes possible, only about 100 are performed each year, due to the critical shortage of donor hearts.

The dream of transplant medicine has long been to make a new heart last a lifetime without the need for immune-suppressing drugs. The idea is to induce “immune tolerance,” tricking the body into believing a new organ is “self.” In a promising development, a small Northwestern University study last year reported achieving tolerance in a handful of kidney transplant patients. In the study, patients received bone marrow stem cells from their kidney donor.”

It’s still early, and we don’t know how much it can apply to heart patients,” says Dr. Kobashigawa, who holds the DSL/ Thomas D. Gordon Chair in Heart Transplantation Medicine. “But this is the holy grail of transplantation. This is what we’re hoping for.”

In the meantime, the search is on for new medicines that are just as effective but less toxic. Two possible candidates, sirolimus and everolimus, already used in cardiac stents, are in clinical use in heart transplant patients. Several antibody drugs are being studied, too. Another goal is to use less of the medicines—something that could be possible with better donor/recipient match- ing. Currently, however, there is simply no time for sophisticated immune-matching tests—once a heart is removed from a donor’s body, it has a mere four hours to make it to its new home.

A new “heart-in-a-box” technology could change that—and soon. Called the Organ Care System, it keeps donor hearts warm and beating instead of on ice, and may extend transplant windows to 10 to 12 hours. Cedars-Sinai is participating in a multicenter clinical trial on the system, and preliminary results are promising.

“Better matching would cut down on acute and chronic rejection and allow us to use fewer medications,” says Lawrence Czer, MD, medical director of the Cedars-Sinai Heart Transplant Program and Jim’s cardiologist. “It’s a huge potential advance; and if it works, it’s just a year or two away.”

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Eight years ago, Jim Stavis became a rare triple organ recipient after undergoing heart, kidney, and pancreas treatment at Cedars-Sinai. Today, he bikes regularly near his home in Calabasas, Calif.

It took some time for Jim to get used to his new heart. For one thing, it was a lot louder than his old one. It was a strange sensation to hear and feel it pumping inside his chest. It seemed to have a mind of its own, too. “It would be time to go to bed, and you’d want your heart to slow down. And it wouldn’t,” he says. “You’d almost have to talk to your heart. It was like, ‘OK, we’re going to bed now!’”

Today, Jim and his heart have no trouble communicating. At 58, he is the picture of health. Tall and fit, his head smoothly shaved, he golfs and bikes regularly. His limitations are minor.

He steers clear of sick people because, when he gets a cold, it takes him longer to recover. He no longer eats sushi. He has high blood pressure, but it is controlled by two medications. Overall, he now takes just six medicines a day, a standard routine for long-term patients. Although about 5 percent of patients have trouble exercising, and some report greater side effects, Jim’s success is common today.

In the living room of the Calabasas home he shares with his wife of 31 years, Renee, he leans back on the sofa and openly shares his journey to near-death and back.

For most of his life, Jim was intensely private about his health, but the transplants changed that. At Paragon Steel, the Long Beach–based steel fabrication company he runs with a partner, Jim began writing about his experiences in the firm’s newsletter— essays on “How to See Sunshine Through the Clouds” and “Finding Your Source of Hope.”

Thoughtful and articulate, with an easygoing smile and calm, soft-spoken demeanor, he calls his optimism his greatest strength. But he is no Pollyanna. He has seen too much reality for that, starting at age 17, when he was diagnosed with Type 1 diabetes. Doctors told Jim he would be lucky to live through his 40s.

“My choice was to let that depress me, or just move forward and hope that medical technology would have an answer for me later,” he says. “I decided to manage my diabetes the best I could, and then live life, but at an accelerated rate. In some ways, it kind of motivated me to get my act together.”

For the next 25 years, Jim lived a normal life, managing his diabetes with daily insulin injections and, later, an insulin pump. Then his doctors’ predictions began coming true. At 42, he had his first cardiac event—his heart briefly stopped while vacationing with family and friends at Lake Arrowhead. Over the next few years, his heart and kidneys began failing, and he spent a year in dialysis before his 2005 transplant.

He was back at Paragon Steel just two months after that transplant. But soon, another challenge loomed: He needed yet another organ—this time, a pancreas. Without it, his ongoing diabetes would likely begin affecting his new heart and kidney. In October 2006, he received a new pancreas at Cedars-Sinai, becoming a rare triple-organ recipient. Again, he had to recover from the pain of major surgery and face a litany of powerful medications, but he no longer needed that insulin pump.

A month later, on Thanksgiving, Jim enjoyed a slice of pumpkin pie for the first time in 35 years. His diabetes was cured.

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“It would be easy to start sweating the small stuff and taking life for granted again,” Jim says. I don’t want that to happen.”

One day, heart transplants may be a thing of the past.

The burgeoning science of tissue engineering already can grow a beating heart in a lab. Lab-grown hearts are not close to human trials yet, but stem cells have shown potential in another area: repairing damaged hearts. In 2012, a groundbreaking, first-in-humans trial led by Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute and the Mark Siegel Family Foundation Distinguished Chair, showed that treating heart attack patients with an infusion of their own heart-derived stem cells significantly shrank scar tissue and helped regrow healthy heart muscle. Dr. Marbán and his team are expanding that research and exploring other avenues, too. One prospect could be to examine whether cardiac stem cells can repair damage that occurs from heart transplant rejection.

“We’ve made tremendous advances in stem cell therapies in the past five years, and initial studies in patients with heart disease show a lot of promise,” says Dr. Marbán. “Different types of heart disease have different needs and we can take a different approach with stem cells. Clinical trials take time. We are a long ways away from being able to transplant a heart entirely grown in the lab instead of one harvested from a donor. However, stem cell therapy could soon be used to restore function to a damaged heart and avoid the need for transplant in some patients.”

One day, heart transplants may be a thing of the past.

Technology has made huge strides in ventricular assist devices and the Total Artificial Heart to support function and blood flow in failing hearts. These can be lifesavers while patients wait for a transplant—and they can sometimes be used permanently—but they lack many dynamic features of a real heart.

Finding viable alternatives to heart transplant is key because of the great shortage of donor hearts. On any given day in the U.S., more than 3,000 people are waiting for a new heart. Only about 2,300 heart transplants are performed each year.

“I think we’ll see big advances from these devices in the next few years,” Dr. Kobashigawa says. “But right now, a transplant is still preferred. There’s nothing better than a beating heart.”

Hanging in Jim and Renee’s kitchen is a framed photo of a handsome, dark-haired teenage boy in his varsity letter jacket: Jim’s heart and kidney donor. The boy, Brice Fabing, was a star field-goal kicker for the football team at Lompoc High School. The 17-year-old senior, who was being recruited for college football opportunities, was killed in a car accident.

After his transplant, Jim sent the Fabings a thank-you letter. They wrote back, and Jim and his family attended what would have been Brice’s graduation in June 2006. When the families met, Brice’s mother had one request: to put her head on Jim’s chest and listen, one more time, to the beat of her son’s heart.

“It’s a weird sensation to know that somebody had to die in order for you to live,” Jim says. “That piece didn’t really hit me as hard until after I met the family. I saw firsthand the void their loss created. I know I’m not responsible for that loss. But I have an incredible sense of gratitude for the gift they’ve given me.”

Jim has seen his kids Ashley and Brian graduate from college and has attended the wedding of his eldest daughter, Jessica.

He admits he gets a little nervous going in for exams. “I like to think I have an unlimited warranty on these organs,” he says with a laugh. His checkups, so far, have been “perfect.” He feels so well he could almost forget he nearly died eight years ago. Brice’s photo is a daily reminder.

“It would be easy to start taking life for granted again,” Jim says. “I don’t want that to happen. I owe my life to that family, and to the doctors and so many others who helped me. I’m lucky just to be here. I don’t ever want to forget that.”

A Delicate Balancing Act

The challenge in post-transplant care remains akin to walking a tightrope: restraining the immune system just enough so that it doesn’t reject the new organ but not so much that the body is defenseless. Doctors have mostly performed this delicate balancing act in the dark.

“We’ve had to monitor immunosuppression by measuring drug levels in the blood,” explains Stanley Jordan, MD, director of Kidney Transplantation and Transplant Immunology at the Cedars-Sinai Kidney and Pancreas Transplant Center. “But that doesn’t tell us how exactly the drugs are affecting the immune system.”

A host of new tools is changing that picture. The ImmuKnow® blood test has been used in recent years to indicate whether a patient’s immunity is too suppressed. Dr. Jordan and his team are now studying new, more sophisticated tests to diagnose undersuppression, too. He estimates the tests will be ready for clinical trials this year.

Meanwhile, the Human Leukocyte Antigen Laboratory at Cedars-Sinai, directed by Nancy Reinsmoen, PhD, is a leader in innovative protocols to facilitate better donor/recipient matching in high-risk transplant cases and to also monitor whether patients are developing worrisome antibodies.

“We’re evolving to a more precise way of monitoring immune response in each patient,” Dr. Jordan says. “It will be more like a personalized medicine assessment of a patient’s risk.”

Advances in immune monitoring will have another benefit for patients: fewer invasive heart biopsies, which are performed frequently in the first year after transplant to screen for rejection.

Earlier this year, Cedars-Sinai completed a randomized clinical trial that showed that the AlloMap® blood test is as effective at detecting heart transplant rejection as biopsy. The test should be in routine use at Cedars-Sinai later this year.

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2 Responses

  1. That quit a good article

  2. Jen Lopez says:

    Great article! Uplifting and promising for us transplant-ees. :-)

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