One day in 1986, David Campbell, MD, stood in an OR at University of Colorado Hospital looking down at a dying patient. The man was only in his mid-50s, but his heart was failing, ruined by severe coronary disease that had ravaged the left ventricle.

Campbell did the only thing possible to save the man’s life. He gave him a new heart. The patient became the first donor organ recipient of UCH’s Cardiac Transplantation Program.

“The transplant went well,” Campbell recalled.

But as was so often the case in the nascent years of transplant medicine, the results fell short of his hopes. Campbell and the transplant team did their best to get the patient through the rigors of organ rejection, but he survived only a week or so – as did the next two.

David Campbell, MD, was surgical director of UCH’s Cardiac Transplantation Program from its inception in 1986 to 2003. He continues to perform pediatric transplants as surgical director of the Cardiac Transplantation Program at Children’s Hospital Colorado.
A decade later, a young resident named Joseph Cleveland, MD, stood in an OR at UCH, assisting on his first heart transplant case. Cleveland peered into the patient’s chest cavity, which held no heart, only bypass tubing.

“I remember thinking we had passed the point of no return,” Cleveland said. “Nothing was going to help except a good heart.”

Another 20 years on, Campbell and Cleveland are still transplanting hearts in the young, the old, and ages in between. Their careers are intertwined: Campbell served as surgical director of the Cardiac Transplantation Program from its inception through 2003, at which point Cleveland took the reins and continues to serve in that post. Campbell is now surgical director of the Cardiac Transplantation Program at Children’s Hospital Colorado. That program has gone on to perform more than 400 pediatric heart transplants, he said.

Long road

Together, the two have participated in or overseen the 506 – and counting – heart transplants at UCH. The program reached the 500-transplant milestone last December. Their memories serve as a reminder that it took many years and painful losses to make heart transplants the reliable procedures that many today take for granted.

The 1986 heart transplant procedures weren’t Campbell’s first. He had teamed up with cardiothoracic surgeon David Clarke, MD, in 1979 to perform two, about a decade after Norman Shumway, MD, performed the first adult human-to-human heart transplant at Stanford University Medical Center in January 1968. The UCH patients Campbell and Clarke operated on suffered hyper-acute organ rejection and died soon after the procedures. At that time, there were no immunosuppressant drugs to fight off rejection.

By the time Campbell launched the program in 1986, the anti-rejection drug cyclosporine had changed the landscape of organ transplantation. But it took years for clinicians to fine-tune administering the drugs, balancing the risk of infection with the necessity of slowing rejection. In addition, UCH and other programs around the country took on extremely sick patients, driving the odds of survival down even further.

“We took on patients we shouldn’t have,” Campbell said. “We had patients sitting in the ICUs who had had two or three previous surgeries, some with increased pulmonary artery pressure. We did the best we could.” He and other transplantation specialists soldiered on in the hope of advancing care, much as liver transplant pioneer Thomas Starzl, MD, had done, first at UCH and later at the University of Pittsburgh.

Early successes

Campbell and his team’s fourth patient, John Mitchell, a middle-aged man with severe coronary disease, received his new heart in 1987 and survived for four years, a quantum leap forward. Then came Jennifer Green. In 1988, she was a 13-year-old from Gillette, Wyo., who was gravely ill with idiopathic cardiomyopathy – disease of the heart muscle with no known cause. She was in the ICU at UCH – the pediatric program did not move entirely to Children’s Colorado until 1990 – when Campbell and colleagues decided her best chance of survival was a heart transplant.

The procedure was not covered by Medicaid at the time, but Wyoming residents raised tens of thousands of dollars on her behalf, and then-governor Mike Sullivan lifted the restriction on a one-time basis. Campbell performed her heart transplant in June 1988. The heart functioned for 22 years before she required a second transplant, again by Campbell, in July 2010.

Now 41, Green still lives in Gillette and works a full-time job as a detention officer. She is still the program’s longest-surviving recipient, Campbell said.

Contacted by phone, Green said she suffered a cardiac arrest in 2012, but that her heart is otherwise “working strongly” and that she has had no problems since.

The original transplant came after her heart problems came up suddenly, Green said. She had a period of flu-like symptoms that eventually were traced to her heart disease. Initially, her providers thought she could manage the condition without a transplant, but her condition worsened rapidly. Green said she doesn’t remember much about getting a new heart at the tender age of 13.

“By the time I was in the hospital, I didn’t care,” she said. “The care I had was very good. I had wonderful physicians and nurses.”

Notable numbers

Green is a standout case in a program that continues to thrive. The number of transplants at UCH more than doubled between 2013 and 2015, from 16 to 34, said Amrut Ambardekar, MD, medical director of the Cardiac Transplant Program and a cardiovascular disease specialist with the CU School of Medicine. One-year and three-year survival rates for patients and grafts meet or exceed the national averages.

Joseph Cleveland, MD, followed Campbell as surgical director of Cardiac Transplantation at UCH in 2003.
“Reaching 500 transplants is a symbolic number that demonstrates we have a longstanding program with a multidisciplinary team that is responsible for our success,” Ambardekar said. “That’s good for patients in the state and in the region who have access to this lifesaving treatment, if it is needed.”

The reasons for the success are varied. Campbell pointed to the introduction of FK506 (tacrolimus), an immunosuppressant medication approved by the FDA in 1994 to combat rejection in liver transplant patients. It was later approved for other organ transplant cases, including heart. Together with cyclosporine, FK506 increased the chances of treating organ rejection, Campbell said.

Cleveland, who estimates he’s performed somewhere between 100 and 150 heart transplants, said building experience is an important component of achieving good outcomes.

“Any time you continue to perform a procedure, you make modifications in your technique,” he said. He noted, for example, that instead of waiting to sew all five connections for the new heart before removing the surgical clamps, he now sews two-and-a-half to allow blood flow to the heart to begin, then sews the remaining two-and-a-half. The result: less ischemic time that could damage the new heart.

“We’re always trying to learn from what we have done in the past,” Ambardekar added. For example, he said, annual cardiac biopsies were long considered routine for heart transplant patients. That’s changed.

“For patients who are stable, we don’t put them through these invasive tests anymore,” Ambardekar said. “We’ve decreased the burden of testing and saved costs while maintaining good outcomes for our patients.”

Keeping the beat

A successful heart transplant does not start or end with a surgeon implanting a new organ. Donor Alliance, the organ procurement organization, for Colorado and Wyoming, plays a key role in the process. In addition, the cardiac transplant team at UCH spends considerable time selecting patients who have the best chance of surviving the procedure and thriving afterward. That requires support from the hospital’s six advanced heart failure-transplant cardiology specialists, as well as nurse practitioners, nurses, social workers, case managers, nutritionists, cardiac rehabilitation experts, pharmacists, and many more.

“When I first started, the surgeon ran everything,” Campbell said. “We didn’t realize how much help we needed from the hard work of our medical colleagues. Our part as surgeons is relatively straightforward. Managing how the body reacts to a heart transplant takes a lot of extra work.”

Amrut Ambardekar, MD, medical director of UCH’s Cardiac Transplantation Program, says transplant is just one of many services the hospital provides patients with advanced heart failure.
Just as the surgeon is only one part of the transplant team, the transplant team is only one part of UCH’s much larger cardiovascular program, Ambardekar emphasized.

He noted that 250,000 people nationally die of heart failure each year, dwarfing the 2,600 or heart transplants that were performed in 2014, according to UNOS (United Network for Organ Sharing).

“Transplants will never solve the problem of heart failure,” Ambardekar said. “We pride ourselves on not wanting to do transplants if we can find other ways to manage patients.” Those strategies include medical management, biventricular pacemakers and interventional procedures such as TAVR (transaortic valve replacement), mitral valve replacement and other recent innovations.

“We pick patients for transplant after we have tried everything else,” Ambardekar said.

Hard choices

The challenges of heart and other organ transplant procedures remain. Despite the significant improvements, rejection is still a delicate and sometimes mysterious problem to manage. Researchers continue to search for clues to explain why some patients’ bodies rebel more fiercely than others at the arrival of a new organ. It’s not surprising that there isn’t an easy answer, Campbell said.

“It took millions of years to put together an immune system,” he said. “It’s the arrogance of man to think that we can dismantle it in just a few years with drugs. It could be that biotechnology allows us to solve the problem faster.”

No amount of technology, clinical expertise, or even flawless teamwork will ever surmount the hard task of selecting patients for transplant. The wide gap between the number of patients and available organs means that providers will inevitably be faced with the question of how to allocate a scarce resource and maximize the chances of success. The hard fact is that a heart transplanted in a patient who is not a good risk for survival is gone forever, leaving another patient to wait while time ticks away.

A multidisciplinary heart transplant team at UCH meets weekly to review cases, with the aim of “ensuring the therapy is offered appropriately,” Cleveland said.

“Donor hearts are a scarce resource,” he said. “It’s a difficult discussion to have with a patient who is not a good candidate for transplant. We have to say to the patient that the organ is not just for you, but that we are also responsible for society at large.”

The hospital’s ventricular assist device (VAD) program has become a strong “bridge to transplant” for patients, Cleveland added. The devices restore and maintain blood flow to kidneys and other organs, thus improving prospects for a successful heart transplant, he said.

Ultimately, the program is part of the hospital’s broader commitment to serving communities in Colorado and the Rocky Mountain region, Cleveland said. Its success hinges on maintaining strong relationships with referring providers.

“We have a vibrant program that is extraordinarily important to the entire community,” he said. “We look at ourselves as privileged and we have a responsibility to do well for patients and their providers.”