A new article published in The New England Journal of Medicine has offered insights into the world’s first pig-to-human heart transplant, which took place earlier this year. The researchers report the patient died unexpectedly nearly two months after the procedure and the exact cause of death is still unclear.
At the beginning of 2022 surgeons in the United States performed a historic procedure, transplanting a genetically modified pig heart into a human for the very first time. The highly experimental procedure was authorized by the US Food and Drug Administration (FDA) under a compassionate use provision. The patient, a man in his 50s with a terminal heart condition, was too unwell to qualify for a conventional heart transplant.
The procedure was initially successful, and within days of the transplant the patient was disconnected from a heart-lung bypass machine that was previously keeping him alive. He began physical rehabilitation and for several weeks displayed impressive signs of recovery.
"We were incredibly encouraged by his progress,” explained Bartley Griffith, the surgeon leading the landmark project. “His heart was strong, almost too strong for his frail body, but he had a strong will to live. He told me he wanted to go home and see his dog, Lucky.”
For around seven weeks the transplant functioned well, and the patient displayed no conventional signs of organ rejection. Sadly, around day 49 the transplanted heart began to display signs of failure and within a fortnight the patient had died.
In a newly published report the researchers behind this world-first procedure describe the conditions that led to the patient’s passing. Officially, the cause of death was heart failure, however, the organ didn’t fail because it was rejected. Upon autopsying the heart, the researchers discovered the transplanted pig heart developed a dramatic thickening of the ventricular walls.
"Our findings on autopsy did not show evidence of rejection," said Griffith. "Instead, we saw a thickening and later stiffening of the heart muscle leading to diastolic heart failure, which means the heart muscle was not able to relax and fill the heart with blood as it is supposed to."
The report notes this tissue behavior is not consistent with what is normally seen when an organ is rejected. At this point it is unclear exactly what mechanism caused this particular organ damage.
Several months ago it was revealed that the transplanted pig heart was found to contain traces of a virus known as porcine cytomegalovirus. It had been hypothesized that this virus could have played a role in the organ failing by stimulating an immune response that subsequently led to heart tissue damage.
However, the new report questions this hypothesis, finding no trace of the virus having spread beyond the pig heart into other organs. It still may be possible the latent virus in the pig heart contributed to the tissue damage but the researchers suggest this hypothesis requires further investigation.
The presence of this porcine virus in the transplanted heart tissue is still a major concern for the researchers as significant testing was undertaken before the organ was used. The donor pig itself was also raised in a secure facility designed to prevent infection from porcine cytomegalovirus.
Muhammad Mohiuddin, co-lead on the research, said the safeguards will be improved in the future to prevent this virus from infecting pigs grown for human transplantation.
"We consider this to be an important learning experience," Mohiuddin said. "Knowing what we know now, we will alter some of our practices and techniques in the future."
Ultimately, this historic procedure is just the first step in a long journey toward successful xenotransplantation. E. Albert Reece, dean of the University of Maryland School of Medicine, singles out the courage of the patient, David Bennett, as fundamental to progressing this field in the hopes of saving more lives in the future.
"This publication will provide vital information for the xenotransplant research community and will play a pivotal role in pushing this field forward," said Reece. "I am so proud of the historic medical achievements made by these leaders in their field and hope these first brave steps, including the courage of Mr. Bennett, will lead to a long-term solution where no patient will die waiting for an organ transplant."
The report was published in The New England Journal of Medicine.
