The first successfully transplanted genetically modified pig heart underwent unexpected electrical changes

Ten months after transplanting the first genetically modified pig heart into a human patient, researchers at the University of Maryland School of Medicine (UMSOM) continue to report new findings
from this landmark transplant.
Their latest study is the first to demonstrate unexpected electrical changes
in pig hearts transplanted into patient David Bennett.
The findings were presented at
the American Heart Association (AHA) meeting earlier this month.

The unexpected cardiac conduction measurements seen on the electrocardiogram (ECG) did not lead to heart failure two months later, but would help inform future xenografts
.

"Electrical signals in pig hearts generally travel very quickly, faster than human hearts, but we found that electrical signals in transplanted pig hearts travel much more slowly in Mr.
Bennett's body," said
study leader Timm Dickfeld, Ph.
D.
, professor of medicine and director of electrophysiology research at UMSOM.
"Sometimes, these signals travel even more slowly
than we would expect from the human heart.
It should be noted that his heart rate is normal, but the time it takes for the current to pass through the heart is extended
.
”

He and his colleagues monitored the patient with an electrocardiogram every day after his
transplant.
ECG monitoring after heart transplantation is a method of
evaluating the electrical conduction system after a heart transplant.
A 12-lead ECG measures the conduction
of the heart at 12 different electrical angles.

In particular, UMSOM researchers reviewed two ECG measurement methods: the PR interval/QRS complex and the QT interval
.
The PR interval and QRS compound measure the time it takes for the current to travel from top to bottom and through the lower cavity, ultimately causing the heart to pump blood into the heart
.
The QT interval measures the time it takes
for the lower chambers of the heart to complete the complete electrical cycle associated with the heartbeat.

"These findings do not appear to be related to pathological outcomes such as heart failure or rejection," said study co-author Bartley Griffith, M.
D.
, professor of surgery and UMSOM's Thomas E.
and Alice Marie Hales Honorary Professor
of Transplantation.
He performed a transplant for Mr.
Bennett
.

Study co-author Muhammad M.
Mohiuddin, MD, said: "Genetic modification of pig hearts to reduce the likelihood of immune system rejection was not the cause
of unexpected ECG results.
" Muhammad M.
Mohiuddin is Professor of Surgery and Science/Program Director of the UMSOM Heart Xenograft Program, whose research led to this historic transplant.

Other faculty analyzed cardiac imaging studies
used to monitor heart function and check for signs of transplant rejection.
Manjula Ananthram, MD, assistant professor of medicine at UMSOM, and her colleagues published a research abstract at the Heart Association meeting showing that echocardiography is more effective than the more invasive "gold standard" procedure cardiac catheterization at measuring the volume of blood pumped into other parts of the body by pig hearts
.
"This is reassuring news that may ultimately mean that we may not need as much invasive monitoring for future patients undergoing xenografts," Dr.
Ananthram said
.
"We are still carefully reviewing our data to determine the best way
to monitor heart function in transplanted pigs.
"

This historic xenotransplant was performed
on January 7, 2022, by faculty members at the University of Maryland Medical Center (UMMC) School of Medicine (UMSOM).
For the patient, David Bennett, surgery was the only viable treatment option
.
He was not eligible for a traditional heart transplant and was in the terminal stages of heart failure, near the end of
his life.
The procedure was approved
under the FDA's Extended Access (Compassionate Use) provisions.

Prior to the transplant, Bennett had been bedridden for eight weeks with a life-threatening arrhythmia and needed to be kept alive
by a cardiorespiratory bypass machine called extracorporeal membrane oxygenation (ECMO).
Within days of his transplant, he stopped ECMO and was involved in active rehabilitation
for nearly two months.
In February, while watching the Super Bowl with a physical therapist, he sang along to "America the Beautiful.
"

The team published preliminary findings
on transplantation in the New England Journal of Medicine last June.

"The transplanted pig heart is exposed to many variables in the new environment of the human body
.
One or more of them may affect the electrical conduction system," said
Mark T.
Gladwin, M.
D.
, vice chancellor for medical affairs at the University of Maryland, Baltimore, and John Z.
and Akiko K.
Bowers Distinguished Professors.
"We need to continue to study this data and share our findings
with the medical community.
"

Dr.
Griffith was selected by the AHA to deliver the annual Glenn Talk at this year's AHA conference in recognition of his career in cardiothoracic surgery
.
In addition to his recent achievements in the field of heart xenografting, he performed the first double lung transplant for a young man with cystic fibrosis in 1983
.
He was also one of the early pioneers in testing an all-artificial heart as a bridge device while waiting for donor hearts to become available
.