2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology ...

terminal heart failure :: Article Creator

Doctors Combined A Heart Pump And Pig Kidney Transplant In Breakthrough Surgery

A 54-year-old New Jersey woman has become the second living person to receive a genetically engineered pig kidney. The surgery, carried out at NYU Langone Health on April 12, also involved transplanting the pig's thymus gland to help prevent rejection.

The patient, Lisa Pisano, had a mechanical heart pump implanted days before getting the transplant. She was facing heart failure and end-stage kidney disease and wasn't eligible for a human organ transplant because of several other medical conditions. Her medical team says she's recovering well.

"I feel fantastic," Pisano said from her hospital bed over Zoom during a press conference on Wednesday. "When this opportunity came, I said, 'I'm gonna take advantage of it.'"

It's the first instance of a patient with a mechanical heart pump receiving an organ transplant of any kind. It is the second known transplant of a gene-edited pig kidney into a living person, and the first with the pig's thymus combined.

The series of procedures was performed over a span of nine days. In the first, surgeons implanted the heart pump, a device called a left ventricular assist device, to replace the function of her failing heart. It's used in patients who are awaiting heart transplantation or otherwise aren't a candidate for a heart transplant. Without it, Pisano's life expectancy would have been just days or weeks.

Close up of surgeon working on organ transplant

PHOTOGRAPH: JOE CARROTTA FOR NYU LANGONE HEALTH

The second surgery involved transplanting the pig organs. The animal's thymus gland, which is responsible for educating the immune system, was placed under the covering of the kidney. The addition of the pig thymus is meant to reprogram Pisano's immune system to be less likely to reject the kidney and hopefully allow doctors to reduce the amount of immunosuppressive drugs she has to take, said Robert Montgomery, director of NYU Langone's Transplant Institute, during the press conference.

It's the latest attempt to transplant an animal organ in a person—a process known as xenotransplantation—as a potential way to address the organ shortage and offer transplants to people who otherwise wouldn't get them. In the US alone, there are more than 100,000 people on the national transplant waiting list, and every day 17 people die waiting for an organ. Strict eligibility criteria means that organs are prioritized for relatively healthy patients, leaving patients like Pisano with few other options.

Starting in 2021, the NYU team began experimenting with transplanting genetically engineered pig hearts and kidneys into deceased humans following brain death. With the consent of their families, the patients were kept on a ventilator so that researchers could assess the viability of the pig organs. In one instance, a pig kidney was able to function in a human body for up to two months—a record for xenotransplantation. In monkeys, pig kidneys have been shown to work for up to two years. Now, scientists are testing whether they can support humans in need of new kidneys.

NYU Doctors Perform First-Ever Pig Kidney Transplant Combined With Heart Pump Implant

Another milestone in pig-to-human transplantation has been crossed, with doctors at New York University Langone today announcing the world's first combination pig kidney and heart pump transplant. The recipient is a 54-year-old woman named Lisa Pisano who was diagnosed with terminal kidney disease and heart failure.

What Made George Takei Write a Children's Book About World War II?

The concept of animal-to-human organ transplantation, or xenotransplantation, has been appealing for decades, given the longstanding shortage of human donor organs. But it's only recently that this approach has started to seem within reach, thanks largely to advances in gene-editing technology that have allowed scientists to create pigs that are more compatible with human biology. One important distinction is that pigs and other mammals normally produce the sugar alpha gal in their muscles, while humans don't.

Over the past few years, various research teams—including scientists at NYU Langone—have been successfully experimenting with these pigs. Their experiments have largely involved animals and a few people declared brain-dead, whose bodies their families allowed to be kept mechanically alive for a time while the donated organ is monitored. More recently, health regulators granted permission for researchers to perform these transplants in living humans on an experimental basis. In March, 62-year-old Richard Slayman became the first living human to receive a genetically modified pig kidney transplant, which was performed by doctors from Massachusetts General Hospital.

Like other recipients of these modified organs, Lisa Pisano had few other options available to her. She had reached end-stage kidney disease that required constant dialysis to manage, and she had a long history of heart problems, including a recent episode of cardiac arrest. But she wasn't a good candidate for a typical heart or kidney transplant due to several chronic conditions and a high level of antibodies to human tissue that would worsen the chances of success.

Pisano likely would have benefited from receiving a left ventricular assist device (LVAD), a heart pump that can take over some of the organ's functioning. These devices are either used to keep people stable while they wait for a heart transplant or as a long-term treatment for people not eligible for one. But her pre-existing kidney disease would typically rule out this option. And without a heart pump, she likely had only days to weeks more to live. The NYU doctors decided to ask Pisano if she would be willing to receive both the pump and a new pig kidney, which she quickly agreed to.

The first-of-its-kind procedure was performed by two separate surgical teams at NYU, over the course of nine days in early April. The heart pump was implanted first on April 4, followed by the kidney transplant on April 12. And though Pisano has experienced some complications and is still being monitored at the hospital, she appears to be recovering well so far.

Though this is the second pig kidney transplant in as many months and fourth pig organ transplant overall, there are some important differences between them. Aside from the added complexity of implanting a heart pump, the NYU team opted to use a pig with only a single gene edit (the removal of alpha gal), while the Mass General team used a pig that had more than 60 genetic changes. The NYU team believes that this one edit will be enough to make pigs compatible with humans, in combination with existing immunosuppressant therapy. They also transplanted over the pig's thymus, an organ that helps train immune cells. Emerging research has suggested such dual transplants can lessen the risk of rejection and improve compatibility between a donor organ and its new host.

Even if things continue to go smoothly, Pisano still has a long recovery and an uncertain future ahead of her. And it will ultimately require successful clinical trials for this technology to become available to the public at large. But NYU researchers and others are already working with the Food and Drug Administration to move ahead with these trials. For her part, Pisano is hopeful about the potential of this treatment for herself and others in her situation. "All I want is the opportunity to have a better life," Pisano said in a statement.

First-Ever Combined Heart Pump And Pig Kidney Transplant Gives New Hope To Patient With Terminal Illness

NEW YORK, April 24, 2024 /PRNewswire/ -- Surgeons at NYU Langone Health performed the first-ever combined mechanical heart pump and gene-edited pig kidney transplant surgery in a 54-year-old woman with heart and kidney failure—a confluence of advances that showcase the possibility and hope of modern medicine.

Robert Montgomery, MD, DPhil, (left) the H. Leon Pachter, MD, Professor and chair of the Department of Surgery and director of the NYU Langone Transplant Institute, and Jeffrey Stern, MD, assistant professor in the Department of Surgery at NYU Grossman School of Medicine, evaluate the surgical site before transplanting the gene-edited pig kidney with thymus into Lisa Pisano on April 12, 2024. Photo by Joe Carrotta for NYU Langone Health.

Doctors performed this feat in two stages: first surgically implanting the heart pump days before embarking on the landmark transplant, which included a gene-edited pig kidney and the pig's thymus gland to aid against rejection. Before the procedure, patient Lisa Pisano, a New Jersey native, faced heart failure and end-stage kidney disease that required routine dialysis. She was not a candidate for heart and kidney transplants because several chronic medical conditions significantly reduced the likelihood of a good outcome and there aren't enough organs for those in need.

Despite these adversities, Pisano has thrived from the love of her grandchildren and eagerly wants to watch them grow up.

"All I want is the opportunity to have a better life," she said. "After I was ruled out for a human transplant, I learned I didn't have a lot of time left. My doctors thought there may be a chance I could be approved to receive a gene-edited pig kidney, so I discussed it with my family and my husband. He has been by my side throughout this ordeal and wants me to be better."

To date, there have been no documented instances of anyone with a mechanical heart pump receiving an organ transplant of any kind. It is only the second known transplant of a gene-edited pig kidney into a living person, and the first with the thymus combined.

"It is incredible to consider the scientific achievements that have led to our ability to save Lisa's life, and what we are endeavoring to do as a society for everyone in need of a life-saving organ," said Robert Montgomery, MD, DPhil, who led the transplant surgery and who is the H. Leon Pachter, MD, Professor of Surgery; chair of the Department of Surgery; and director of the NYU Langone Transplant Institute. "This could not have been done without the dedication and skill of the many talented physicians, researchers, nurses, health administrators, and perioperative care teams at NYU Langone Health, and the numerous pioneers who came before us."

Nearly 104,000 people are on the waiting list for a transplant, with 89,360 of those waiting for a kidney. Nearly 808,000 people in the United States have end-stage kidney disease but only about 27,000 were able to receive a transplant last year.

Story continues

Multimedia Materials Available

Multimedia materials, including photos and a B-roll package, are available for download.

About the Procedures

The series of procedures were performed by two separate surgical teams over the course of nine days.

In the first procedure, surgeons implanted the heart pump, a device called a left ventricular assist device (LVAD), which is typically used in patients who are awaiting heart transplantation or otherwise ruled ineligible to receive a heart transplant.

Without a heart pump Pisano's life expectancy would have been measured in days or weeks.

Nader Moazami, MD, chief of the Division of Heart and Lung Transplantation and Mechanical Circulatory Support for the Department of Cardiothoracic Surgery at NYU Grossman School of Medicine, and Deane E. Smith, MD, director of mechanical circulatory support, performed the LVAD surgery on April 4, 2024, in NYU Langone's Kimmel Pavilion in New York.

The second procedure was a xenotransplant, which is a transplant of an organ between different species. Dr. Montgomery led the xenotransplant on April 12, 2024.

Pisano had high levels of harmful antibody to human tissue, but not to gene-edited pig organs. It would have taken years for her to find a match for a human kidney transplant. Dr. Montgomery approached United Therapeutics Corporation and determined an investigational gene-edited pig kidney with thymus was available and matched. Although chronic kidney failure typically rules patients out from receiving an LVAD, the hope of the transplant preventing her from needing dialysis was a key consideration.

"Without the possibility of a kidney transplant, she would not have been eligible as a candidate for an LVAD due to the high mortality in patients on dialysis with heart pumps," said Dr. Moazami. "This unique approach is the first time in the world that LVAD surgery has been done on a dialysis patient with a subsequent plan to transplant a kidney. The measure for success is a chance at a better quality of life and to give Lisa more time to spend with her family."

Pisano received the organ from a pig genetically engineered to disrupt, or "knock out," the gene responsible for the production of a sugar known as alpha-gal. In previous studies at NYU Langone, it was demonstrated that removing alpha-gal was sufficient to prevent an antibody reaction that can cause immediate, or hyperacute, rejection of the xeno-organ. The donor pig's thymus gland, which is responsible for educating the immune system, was surgically placed under the covering of the kidney to reduce the likelihood of rejection. The xenokidney and the thymus tissue combined are called a UThymoKidney™. The gene edits, pig breeding, and production of the investigational UThymoKidney™ used in this procedure were performed by United Therapeutics Corporation. No other unapproved devices or medications were used in the procedure.

"By using pigs with a single genetic modification, we can better understand the role one key stable change in the genome can have in making xenotransplantation a viable alternative," said Dr. Montgomery. "Since these pigs can be bred and do not require cloning like more-complex gene edits, this is a sustainable, scalable solution to the organ shortage. If we want to start saving more lives quickly, using fewer modifications and medications will be the answer."

The effort required rigorous preparation, clearance by NYU Langone's institutional review board, and approval by the FDA through its Expanded Access Program—sometimes called "compassionate use" and meant for patients who have a serious or immediately life-threatening condition.

Additional investigators in the xenotransplant included Adam Griesemer, MD; Jeffrey M. Stern, MD; Bonnie E. Lonze, MD, PhD; Nicole M. Ali, MD; Sapna A. Mehta, MD; Vasishta Tatapudi, MD; Massimo Mangiola, PhD; Elaina Weldon, MSN, NP; Karen Khalil, PharmD; Jacqueline Kim, MD; Ian S. Jaffe; Imad Aljabban, MD; Aprajita Mattoo, MD; Rebecca Esker, PharmD; Nikki Lawson, RN; Jef Boeke, PhD; Brendan Keating, PhD; and Alexandre Loupy, MD, PhD, director of the Paris Institute for Transplant and Organ Regeneration.

The NYU Langone Transplant Institute collaborated with David Sachs, MD, and Megan Sykes, PhD, of the Columbia Center for Translational Immunology (CCTI) at Columbia University Irving Medical Center. They both helped to develop a pig thymus–kidney concept with the intent of reducing the amount of immunosuppression. This procedure marked the first-ever human transplant of a pig-derived thymokidney.

NYU Langone Health acknowledges United Therapeutics Corporation for the UThymoKidney™ and financial support provided for xenotransplantation research initiatives and this procedure, as well as the support of Apellis Pharmaceuticals Inc.'s Compassionate Use Program, which provided Empaveli®, also known as pegcetacoplan, a medicine used in the off-label treatment to prevent rejection of the organ.

Progress in Xenotransplantation

This complex intervention marks the sixth human xenotransplant surgery performed by the NYU Langone Transplant Institute and orchestrated by Dr. Montgomery, who has spent much of his career studying innovative approaches to expanding the organ supply and performed the world's first gene-edited pig-to-human organ transplant on September 25, 2021, in a neurologically deceased person with a beating heart. The same gene-edited pig kidney and thymus were used in that procedure and in a second similar procedure on November 22, 2021. Surgeons at NYU Langone then performed two gene-edited pig heart transplants in summer 2022. Last year, a 61-day study of a gene-edited pig kidney xenotransplant in a recently deceased man showed optimal performance with standard-of-care immunosuppression.

The NYU Langone Transplant Institute has performed more xenotransplantation surgeries in humans than any other institution to date. Before this most recent surgery, however, five were done using a special protocol involving recently deceased people, in collaboration with their families, to study the effectiveness and viability of gene-edited pig organs in humans before transplanting them into living people.

"Without the generosity and altruism of those who participated in our series of decedent model studies, this moment in transplantation would not have been possible," said Dr. Montgomery. "We eagerly await the opportunity to participate in clinical trials, under the FDA's guidance, to continue learning more about the possibility of a new, sustainable source of organs for all those without much time left."

About the NYU Langone Transplant Institute

The NYU Langone Transplant Institute offers the highest-quality kidney and lung transplantation programs in the nation, according to federal quality data, while the heart and liver transplant programs stand out in national survival rates and in their success getting patients off the waitlist. In 2023, the institute performed 576 organ transplants. NYU Langone's heart, kidney, liver, lung, and pancreas transplant programs are approved by the Centers for Medicare & Medicaid Service (CMS), which means they have met the stringent volume, process, quality, and survival outcome requirements of CMS regulation.

Media InquiriesColin DeVriesPhone: 212-404-3588Colin.DeVries@NYULangone.Org

NYU Langone Health (PRNewsfoto/NYU Langone Health)

Cision

View original content to download multimedia:https://www.Prnewswire.Com/news-releases/first-ever-combined-heart-pump-and-pig-kidney-transplant-gives-new-hope-to-patient-with-terminal-illness-302125248.Html

SOURCE NYU Langone Health System

View comments

Search This Blog

Poliomyelitis