Life Goes On

From the Winter 2018 edition of Vanderbilt Medicine Magazine

Ahmya Calloway. Photo by Daniel Dubois.

 

Ahmya Calloway, 13, had end-stage renal failure that impacted her heart function. The Chattanooga, Tennessee, native had been cared for at Monroe Carell Jr. Hospital at Vanderbilt since she was 2 years old.

Medication was the first thing Calloway’s doctors tried, but over time her health declined to the point that she needed hemodialysis. Soon after it was begun, Calloway’s heart began to fail. She needed a new heart and kidney.

In May 2016, the teenager became Vanderbilt’s first pediatric dual heart/kidney transplant recipient. At the time of her transplant, United Network for Organ Sharing data show there had been just 41 heart/kidney transplants in children younger than 18 performed in the United States since 1988.

“It is very rare for children to receive a simultaneous heart and kidney transplant,” said Calloway’s pediatrician Kathy Jabs, MD. “We have had patients who received a heart transplant who needed a kidney later in life, but never at the same time. Ahmya was our first, and she is doing wonderfully.”

 

Excellence in innovation

The Vanderbilt Transplant Center (VTC) has experienced many “firsts” over the last couple of years. The longest continuously running transplant program in the Southeast, VTC was established nearly 30 years ago as a multidisciplinary, full-service center for transplantation. The center has made significant advances in education and research and dramatically changed the lives of thousands of patients and their families.

At the core of the center’s success is innovation, a key theme of the charter written in 1989. Lauded for outcomes and patient care, the center’s ability to offer state-of-the-art advances continues to be central to its mission — to propel and direct organ transplantation, research, medicine, technology and education into the future while securing its place as the recognized leader and national authority of multi-organ transplantation.

Seth Karp, MD, is the director of the Vanderbilt Transplant Center, one of the largest organ transplant programs in the Southeast. Photo by Joe Howell.

“We have come a long way since the inception of the program and we continue to integrate the newest innovative and technological solutions in our practices to help us care for our patients,” said Seth Karp, MD, H. William Scott Jr. Professor and chair of the Department of Surgery and director of the Vanderbilt Transplant Center. “As we grow, our ability to perform cutting-edge research and technology increases.

“Innovation to me is anything that helps patients that hasn’t been done before. We are poised to continue our efforts to combine emerging science with clinical delivery.”

Vanderbilt performs about 450 solid organ transplants a year. The center’s adult clinical program comprises kidney, pancreas, combined kidney/pancreas, heart, lung, combined heart/lung, liver, combined heart/ liver and combined heart/kidney. The center’s pediatric clinical program comprises kidney, liver, heart transplantation and dual organ transplant.

Not only does the Transplant Center offer the most novel therapies and technology available, it also incorporates patient support services in areas that include psychiatry, ethics, pharmacy, infectious disease, social work, quality of life and return-to-work. These programs have played a critical role in helping move the center forward and served to set it apart from peer institutions.

“We are a center for training and education,” said Ed Zavala, administrator for VTC. “We recognize the value of treating and supporting our patients as a whole person, which goes beyond the actual act of transplantation.

“We know we can save lives; we have the technology and skills to do that. What we also focus on is the quality of a patient’s life after transplant. How can we make their lives better? It starts even before they begin the transplant process and we work with them beyond that to help them gain a normal level of quality of life.”

 

Ex-vivo perfusion

For decades the miracle of organ donation has relied on an ice cooler to preserve and transport an organ from donor to recipient.

Until now.

Vanderbilt is participating in two separate clinical trials testing novel preservation and transport devices for both hearts and livers. Both studies have the potential to revolutionize transplantation.

The trials will use devices to keep the organs functioning during transport from the donor to the recipient by mimicking the human body. The revolutionary devices continuously perfuse warm, oxygenated,

nutrient-rich blood and nutrition to the organ to optimize function.

“Ex-vivo perfusion is the next big thing in heart transplantation,” said Ashish Shah, MD, director of Heart Transplant and Mechanical Circulatory Support. “The idea is to expand the donor pool. Opening up the criteria for heart donors will do two things: get people transplanted faster because the geographical area has increased with the removal of the time constraints; and secondly, it allows us to create new knowledge in this innovative field of organ reconditioning and resuscitation.”

Ex-vivo perfusion will advance heart transplantation, says Ashish Shah, MD. Photo by Anne Rayner.

Currently, surgeons work to transplant a heart within four hours after it has been harvested from the donor’s body. VTC is one of nine centers across the United States to participate in the EXPAND Heart Pivotal Trial using a device by TransMedics called the Organ Care System (OCS). The device has the ability to increase the amount of time that a heart can be maintained outside the body in a condition suitable for transplantation, providing surgeons the opportunity to assess the heart’s function outside the body and allow for resuscitation, which could potentially improve function after removal from the donor.

“What if we could use this platform to repair hearts?” asked Shah, who holds the Alfred Blalock Endowed Directorship in Cardiac Surgery. “When I look at this technology I am inspired by the extraordinary possibilities of what this holds for the future of transplantation.

“At Vanderbilt we ask and try to answer the relevant questions. If you don’t have a group of people who are thinking in those innovative ways or thinking about innovation, you are just doing heart transplants.”

Like the heart, VTC’s liver program will also test a novel therapy using the OrganOx metra® device, which has the capability of preserving the liver for up to 24 hours outside the body, unattainable with standard preservation methods.

Vanderbilt is among 15 centers, and the only institution in Tennessee, enrolling patients in an investigational, randomized and controlled nationwide study.

“I believe perfusion is the future of organ transplantation,” said Sophoclis Alexopoulos, MD, chief of Vanderbilt’s Division of Hepatobiliary Surgery and Liver Transplantation. “This technology has the potential to increase the donor pool as well as maximize recipient outcomes.

“There are so many future possibilities that this kind of technology can bring. The potential to modulate or modify ex-vivo organs, the potential capability of rehabilitating damaged livers for transplantation and the possibility of modulating the immune profile of the livers to facilitate compatibility issues.”

 

A chance to grow up

Bret Mettler, MD, assistant professor of Cardiac Surgery at Monroe Carell Jr. Children’s Hospital at Vanderbilt, envisions a bright future for children requiring cardiac transplantation utilizing different sources of technologic advancement.

“In pediatrics, we often utilize existing technology, most often designated for much larger patients, and modulate it into therapies that can work for children,” he said. “It’s what we have been doing for years within the field of mechanical support as a bridge to transplantation.

“At Vanderbilt we are fortunate to have one of the largest mechanical support programs in the United States. Our partnership with our adult mechanical support program has been instrumental in maximizing benefits for our patient population.”

While the lack of research and design dollars for new advancements in pediatric heart transplantation continues to be one of the biggest barriers to innovation, Mettler said there is good news on the horizon.

One novel therapy that is showing promise is ABO-incompatible heart transplants. Children’s Hospital performed the state’s first procedure in 2013. It has done five to date. The procedure  — reserved for children 2 years old and younger who have not yet developed significant levels of anti-ABO antibodies — helps a transplant recipient tolerate an organ from a donor whose blood type is incompatible.

In the past, children listed as ABO incompatible for heart transplants were at the “bottom of the list” in terms of matching with a donor. But recent outcomes showing improved survival rates have sparked growing interest in the technique and a reallocation strategy for patients who can receive this type of heart transplant.

Mettler said he is buoyed by the prospect of two additional advancements: the creation of a new heart/liver transplant program for patients with congestive hepatopathy and a new device trial for pediatric heart failure patients.

“If you want to talk about where we are pushing the envelope for our kids, we are starting a true heart/liver transplant program for children,” said Mettler. “Roughly 20-30 percent of our congenital heart volume is made up of patients who have a single ventricle physiology and over time leads to congestive hepatopathy.”

The program, the first in the area, will cater to patients with congestive hepatopathy, a backup of blood in the liver, resulting from heart failure. This disorder eventually causes cirrhosis of the liver with some patients requiring a combined heart/liver transplant.

The need for circulatory support devices for small children with advanced heart failure, most of whom will need a heart transplant, is substantial and has been growing over the past decade.

Vanderbilt was the first in Tennessee to implant the Berlin Heart,

a smaller version of left ventricular assist devices (LVADs) used in adults. The life-saving device is the first of its kind for small infants and children and buys patients time until a donor heart can be found. A plastic tube attaches to the heart and major vessels to divert blood briefly from the body to a pumping chamber that rests outside the body. The pump gives the blood a stronger push than the heart can muster to deliver oxygen and nutrients needed by the brain and vital organs to sustain life.

But the need for additional support led to the creation of a continuous flow device that is set to be tested this year. Vanderbilt is one of the 16 sites for the PumpKIN (Pumps for Kids, Infants and Neonates) trial. The pump, the size of a paper clip, is fully implantable and supports the circulation of infants and children with advanced heart failure.

 

Lifesaving collaboration

The advancements among the various transplant programs at Vanderbilt give Karp pause and he quickly credits the many team members working to progress transplantation, quality of patient care and outcomes. Among those included in his accolades are members of the transplant teams at the VA Tennessee Valley Healthcare System (VA).

“At Vanderbilt we are honored to collaborate with the outstanding physicians at the VA to deliver state-of-the-art care to our nation’s veterans,” said Karp. “We are the only center in the country that offers bone marrow, liver, kidney, heart, and multiple solid organ transplants to VA patients. We are extraordinarily proud of the trust the VA has placed in our clinical programs over many years.”

In 2017, the dual organ heart/kidney transplant using hepatitis C-positive organs for a disease-free patient was a first for VTC. Traditionally organs infected with hepatitis C, the most common blood-borne infection, would only be offered to patients who also have the disease. If the organ was not suitable for that patient population, it would be discarded.

VTC had already demonstrated the ability to transplant and manage both liver and hearts from a hepatitis C-positive donor into a non-positive recipient with successful outcomes due largely to the advances in anti-viral drug therapies that cure hepatitis C (HCV).

It was a concept learned from the VA, said Joseph Awad, MD, chief of transplantation at the VA. He said the ability to transplant hepatitis C organs into a non hepatitis C patient was a game changer for his program in 2016.

“Hepatitis C has been a major issue for the past 20 or so years,” said Awad. “It’s only been in the last three to four years with the availability of great new medications and it has changed everything. The use of these new antiviral drugs is helping to eradicate HCV, extend the lives of patients already transplanted with HCV, reduce the demand for livers and open up transplantation for more people.”

The Nashville VA, home to the largest transplant center in the country, has blazed a trail in the use of telehealth as a way to provide care to its patients from around the country. The opportunity to consult with patients prior to travel to the VA hospital has allowed for more efficient visits as well as the ability for team members to identify patients who are not acceptable transplant candidates, which saves on unnecessary travel and time for the patients.

But one of the greatest innovations, according to Awad and VA colleague and cardiologist Henry Ooi, MD, is the relationship that began decades ago between the two campuses. Both physicians are part of and work closely with the transplant program at Vanderbilt.

Situated adjacent to VUMC, the Nashville VA is one of a few facilities nationwide to provide transplants for veterans. Modeled after VTC, the Nashville VA is also the only comprehensive transplant center in the VA system, providing all of the most common transplants – kidney, heart, liver and stem cell.

“The collaboration between the two entities has been lifesaving for our patients,” said Ooi, medical director of the advanced heart failure and heart transplant program at the VA.

“Much of what we are able to accomplish, we do in concert with Vanderbilt. We are the only VA heart transplant center that offers dual organ transplants. Our survival rates and outcomes are above the national average. Our shared care model, our proximity and relationship with Vanderbilt are all a part of what makes our transplant program successful,” said Ooi.

The longstanding relationship between the two campuses is a source of pride for Karp. He said the collaboration has provided veterans access to the transplant services at Vanderbilt while enriching the educational opportunities for the center’s medical students and fellows.

As an academic medical center, Karp said innovation is present in most every aspect of the transplant center’s programs. A few areas Karp is focused on include: treating kidney transplant patients with significant obesity; liver regeneration research and having a voice in the national debate in liver allocation which could potentially change the way the UNOS distributes livers that would negatively impact patients listed at Vanderbilt and across the Southeast.

“Our goals are to take outstanding care of our patients and help lead advances in transplant practice, training and research,” said Karp. “We are always thinking about ways to improve this field in a significant way. Sometimes that is through treatment options, technology, relationships, research and advocacy, but at the center of all of this is the patient.”