A genetically modified pig heart transplanted into a severely ill person took longer to generate a heartbeat than those of typical pig or human hearts, research showed, another potential challenge for doctors aiming to conduct clinical trials of pig-organ transplants.
Doctors took daily electrocardiograms of David Bennett, a 57-year-old handyman and father of two who received a gene-edited pig heart in an experimental surgery at the University of Maryland Medical Center in Baltimore in January. Mr. Bennett died in March from heart failure, but doctors still aren’t sure why the pig heart thickened and lost its pumping ability.
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Doctors involved in the groundbreaking surgery have been studying data from Mr. Bennett’s case, which is being closely watched in the wider transplant community. Researchers reported in May that a common pig virus was detected in the pig heart transplanted into Mr. Bennett. They said there is no evidence the virus infected Mr. Bennett, but its presence in the pig heart could have caused inflammation that contributed to the cascade of events that led to his death from heart failure.
Researchers analyzed Mr. Bennett’s EKG data as part of efforts to understand his decline after the transplant, direct future research and determine a possible path toward opening clinical trials. Widely used tests that measure electrical signals that cause the heart to beat, EKGs can help diagnose heart attacks, irregular heart rhythms and other possible abnormalities.
Researchers reported unexpected findings in two aspects of Mr. Bennett’s EKG data: the time it takes electricity to travel from the top to the bottom chamber of the heart and across the bottom chambers, which pumps blood through the heart, and the time it takes the lower chambers of the heart to go through a full electrical cycle, which is associated with a heartbeat.
The time intervals are typically shorter in pig hearts that are in pigs. But they took longer in the gene-modified pig heart inside a human. The time for the electricity to travel through the heart’s electrical system and generate a heartbeat also took longer than what is typical for human hearts, said Timm Dickfeld, a professor of medicine and director of electrophysiology research at the University of Maryland Medical Center, who was the leader of the EKG study.
What that might mean in the future for doctors caring for patients with gene-modified pig heart transplants is uncertain, said Paul Wang, director of the Stanford Cardiac Arrhythmia Service and a professor of medicine and bioengineering at Stanford University, who examined the data but wasn’t involved in the study.
“It has only been done once,” Dr. Wang said. “It needs to be done many more times for us to understand what these differences mean.”
The EKG data haven’t been published or undergone an outside vetting process. They are being presented by the Maryland team at an American Heart Association annual meeting starting Nov. 5. The Maryland team said they are studying the significance of the findings and hope to gather more data in future studies.
The fact that the electrical signals traveled through Mr. Bennett’s heart more slowly than expected “did not appear to be associated with a pathological outcome,” said Bartley Griffith, co-director of the cardiac xenotransplantation program at the University of Maryland School of Medicine, who performed Mr. Bennett’s transplant surgery.
Dr. Griffith added that if Mr. Bennett had survived longer and the time intervals became even slower, a pacemaker might eventually have become necessary.
Researchers have tried for decades to develop the transplantation of organs between different species, or xenotransplantation, to address a chronic shortage of organs. More than 3,500 people are on the waiting list in the U.S. for a heart transplant, according to a 2022 update from the American Heart Association.
Megan Sykes, director of the Columbia Center for Translational Immunology in New York, said that although pigs are similar to humans in organ size and physiology, the EKG data illustrate that there are differences that may only emerge after doing transplants into humans.
“We have reached the point where we need human studies as well as animal studies,” Dr. Sykes said.
The Maryland team and other groups have met with the Food and Drug Administration recently to discuss how to start small clinical trials of genetically modified pig organs. The FDA has requested additional data from the Maryland team in baboons, said
Muhammad Mohiuddin, the scientific program director of cardiac xenotransplantation at the University of Maryland School of Medicine. Dr. Mohiuddin said they plan to gather additional EKG data as part of the research.Write to Amy Dockser Marcus at amy.marcus@wsj.com
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