Pig’s Heart Took Longer to Generate a Beat in Transplant Patient

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.

Why Scientists Are Turning to Pigs for Organ Transplants

Human donor organs are in short supply for life-saving transplants. Pig organs have emerged as a potential alternative, in part because pigs are easy to breed and their organs are similar in size to those of humans. And scientists are now able to edit pig genes in ways that make the organs more suitable for transplantation into people.

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle.

Here’s one approach:

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs— contain the edited genes.

Crispr acts like scissors cutting DNA at a specific place

scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells— including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

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