Heart transplant

The world’s first pig heart transplant recipient died of heart failure, not organ rejection

David Bennett Sr, an American citizen who made history as the first person in the world to receive a genetically modified pig’s heart, died of heart failure and not due to organ rejection, have concluded surgeons from the University of Maryland. Bennett, 57 and suffering from terminal heart disease, received a heart from biotech company Revivicor, which produces genetically modified pigs, in January this year. Organ transplantation has demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body, doctors said after the rare and successful operation. But his death two months later called into question the procedure. Earlier, researchers pointed to a pig virus – a preventable infection linked to devastating effects on transplants – as the possible reason for his death.

Now the researchers say the transplanted pig heart functioned well for several weeks and showed none of the typical signs of rejection by the patient’s body, even when carefully examined during an autopsy. Surgeons concluded that the patient died of heart failure likely caused by a complex set of factors.

“Our autopsy results did not show evidence of rejection. Instead, we saw thickening and then stiffening of the heart muscle leading to diastolic heart failure, which means that the heart muscle has no been able to relax and fill the heart with blood like it’s supposed to,” said Bartley Griffith, MD, a professor at the university’s medical school.

The team explained several factors that may have contributed to the development of heart failure, including the use of intravenous immunoglobulin, IVIG, a drug that was given to the patient twice during the second month after the transplant to help prevent rejection and infection.

The drug contains antibodies against pig cells that may have interacted with the pig’s heart, causing a reaction that damages the heart muscle. The heart was also found to contain DNA evidence of a latent porcine virus called porcine cytomegalovirus (pCMV) through highly sensitive tests that were first detected several weeks after surgery and later confirmed during organ autopsy.

“We consider this to be an important learning experience. Knowing what we know now, we will modify some of our practices and techniques in the future,” added Muhammad M. Mohiuddin, professor of surgery at the university.

The new finding comes amid reports from the US Food and Drug Administration (FDA) considering approving human clinical trials for pig-to-human organ transplants.

The large-scale transplants have “raised public awareness of the field” and “made it an optimal time for public conversation” and clinical trials, Wilson Bryan, director of the FDA’s Office of Tissues and Advanced Therapies at Silver Spring, Maryland, at a recent US FDA consultative meeting.

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