What are the lessons after first pig heart transplant in human patient failed?

Scientists have analysed what went wrong when the man who received the world’s first transplant of a genetically modified pig’s heart, died two months after the operation.

Describing the donor, David Bennet Sr, as “a hero volunteer,” the leader of the research team said they want their next patient to “thrive.”

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Bennett was in end-stage heart failure and nearing the end of his life. He did not qualify for a traditional heart transplant.

He was given the xenotransplant – transplants from one species to another – ­­by US University of Maryland School of Medicine (UMSOM) physician-scientists in January 2022 to treat a terminal heart condition.

The 57-year-old experienced strong cardiac function after the surgery, with no obvious sign of rejection for seven weeks. He died on March 8, 2022 of heart failure.

Researchers outlined several overlapping factors which they believe led to Bennett’s heart failure.

Among them were his poor health prior to the transplant leading him to become severely immunocompromised. His poor condition limited the use of effective anti-rejection treatments. As a result, the patient likely became more vulnerable to rejection of the pig heart from antibodies produced by the immune system.

The team also found evidence that intravenous immunoglobulin, a drug containing antibodies used to normalise a compromised immune system, may have contributed to damage to the heart muscle cells.

Also present in the patient were signs of a latent virus, called porcine cytomegalovirus, in the pig heart which may have contributed to its dysfunction.

By studying the physiological processes that led to Bennett’s death, UMSOM researchers hope that they can increase the odds of success in future transplants.

The findings of their extensive analysis have been published in medical journal the Lancet.

“Our paper provides crucial insight into how a multitude of factors likely played a role in the functional decline of the transplanted heart,” says lead author Muhammad M. Mohiuddin, MD, a professor at UMSOM. “Our goal is to continue moving this field forward as we prepare for clinical trials of xenotransplants involving pig organs.”

Mohiuddin is the Program Director of UMSOM’s Cardiac Xenotransplantation Program which aims to make viable the use of non-human organs to save lives.

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“We were determined to shed light on what led to the heart transplant dysfunction in Mr. Bennett, who performed a heroic act by volunteering to be the first in the world,” says co-author Professor Bartley Griffith, MD. “We want our next patient to not only survive longer with a xenotransplant but to return to normal life and thrive for months or even years.”

As part of their analysis, the researchers performed extensive tests on the limited available tissues from the patient. They also analysed imaging tests like echocardiography and confirmed that the heart was functioning well until day 47 after the surgery.

“Valuable lessons can be learned from this ground-breaking surgery and the courageous first patient, Mr. Bennett, that will better inform us for future xenotransplants,” says UMSOM Dean Mark T. Gladwin, MD. “In the future, our team of surgeon-scientists will utilise newly designed immune cell assays to monitor the patient more precisely in the days, weeks, and months following the xenotransplant. This will provide stricter control of the earliest signs of rejection and the promise of a truly lifesaving innovation.”