Modified porcine-human heart transplantation underwent unexpected changes in the cardiac conduction system

According to preliminary research to be presented at the American Heart Association's 2022 scientific meeting, in the electrocardiogram of the first pig-to-human transplant, heart rate measurement found unexpected differences
between the conduction system of the heart of a transgenic pig and the conduction system of a heart of a non-transgenic pig.
The conference, which took place in Chicago on November 5-7, 2022 and was conducted online, is the latest in cardiovascular science.
An important global exchange for
scientific advancements, research and updates on evidence-based clinical practice.

Xenograft — the process of transplanting organs from one animal species into another — took a leap forward in January 2022 when a 57-year-old man with advanced heart disease received his first genetically modified pig heart transplant
.
The patient survived 61 days
.

Researchers have been
studying this new pig-to-human transplant technique for more than 30 years.
If successful, obtaining hearts from genetically altered pigs could one day become a reality
.
The pigs' genes were altered and could be safely transplanted into
humans.

"There are several potential challenges
to transplanting a pig heart into a human body.
Any transplant, including this, always carries a risk of rejection, a potential risk of infection, and a third is an abnormal heart rhythm, and that's what electrocardiography (ECG) does," said Timm Dickfeld, MD, professor of medicine and research director
of electrophysiology at the University of Maryland School of Medicine in Baltimore.
"This is indeed a new discovery that the ECG parameters after pig heart transplantation to humans are so different
from the common native pig heart ECG parameters.
"

ECG monitoring after heart transplantation is one way to
evaluate the electrical conduction system after heart transplantation.
A 12-lead ECG measures the conduction
of the heart at 12 different electrical angles.

Specifically, the researchers reviewed two ECG measurements: the PR interval/QRS complex and the QT interval
.
The PR interval and QRS complex measure the time it takes for current to travel from the top to the bottom chamber and through the bottom chamber to pump blood into the heart
.
The QT interval measures the time it takes for the lower chambers of the heart to complete a complete electrical cycle associated with the
heartbeat.

In this study, ECG data from transplant patients is usually collected once a
day after transplantation.
Previous studies have shown that the ECG parameters of pig hearts in pigs have shorter PR intervals (50 ~ 120 ms), shorter QRS (70 ~ 90 ms) and shorter QTs (260 ~ 380 ms).

"In contrast, the first transgenic xenograft ECG found a PR interval of 190 milliseconds, a QRS duration of 138 milliseconds, and a QT interval of 538 milliseconds, which is longer
than expected for pig hearts in pigs," Dickfield said.

"In the human heart, when these parameters become longer, this may indicate signs of
electrical or myocardial disease," he said.
"Pig heart ECG parameters are extended to what we see in the human heart, and often these measurements are even beyond what we think of as normal for
the human heart.
"

In addition, continuous ECG measurements showed that the extended PR interval after transplantation remained stable, averaging about 210 milliseconds
.
The duration of QRS was extended by about 145 milliseconds, but shortened
within 61 days of transplantation.

"For example, when the muscles and electrical systems themselves are diseased, the duration of QRS may be prolonged, which is why it takes a long time for electricity to travel from one cell to another and from one side of the heart to the other
," Dickfield said.
"In general, we hope that QRS measures will not drag on too long
.
"

Finally, the study showed an average increase in QT duration of about 509 milliseconds, accompanied by dynamic fluctuations
.
QT duration is lowest
on day 14.
"In the human heart, QT duration is associated
with an increased risk of abnormal heart rhythm," Dieckfield said.
"In our patients, the prolongation of QT measurements is worrying
.
While we saw some volatility, the QT index remained extended
throughout the 61 days.
”

The researchers believe that these findings provide the basis for future research to better understand the effects of xenografts on the heart's electrical system and to better prepare
for future xenograft cases.

According to the American Heart Association's 2022 Heart Disease and Stroke Statistics Update, 2020 (the latest data available) saw the highest number of heart transplants in the United States at 3,658
.
According to the latest data, as of February 2021, there are 3,515 people on the heart transplant waiting list and 49 people
on the heart-lung transplant waiting list.

"The ultimate goal is that if someone needs a heart, xenograft may be an option
," Dickfield said.
"We need to make xenografts safer and more feasible in these challenging areas: rejection, infection, pumping problems and, of course, abnormal electrical signals and heart rhythms
.
"

The main limitation of the study is that this is the first study of its kind in a single patient
.
Future research will have a better knowledge base
.

"This is a real milestone in xenotransplantation research, which refers to the transplantation of organs from one species to another, in this case, from pigs to humans
.
The key steps in the success of these surgeries focus on
genetic manipulation to reduce organ rejection.
Addressing the issue of rejection may eventually lead to the use of this approach to help large numbers of patients with advanced heart failure," said Paul J.
Wang, MD, FAHA, who was not involved in the study, director of the Stanford Arrhythmia Service, professor of medicine and bioengineering at Stanford University, and editor-in-chief of Circulation: Arrhythmias and Electrophysiology, a journal of
the American Heart Association.

"It would be very interesting to understand the factors that influence the change of parameters, comparing the value of pigs in pigs and the value
of pigs in people.
We wanted to see how they reflected factors
such as rejection and hemodynamic status.
"Further analysis of the ECG, including ST-T wave abnormalities, may also provide unique insights
.
"