Heart transplant

Modified pig-to-human heart transplantation showed unexpected conduction system changes

Research Highlights:

  • Electrocardiogram (ECG) measurements taken after the first pig-to-human heart transplant revealed electrical conduction characteristics significantly different from those observed in native pig hearts (pig heart transplanted into a pig).
  • Common ECG measurements are typically shorter in a pig than in a human, but, during the January 2022 pig-to-human heart transplant, these ECG measurements were unexpectedly prolonged.

Embargoed until 4am CT/5am AND, Monday, October 31, 2022

DALLAS, October 31, 2022 – Heart rate measurements in electrocardiograms from the first pig heart transplant in humans have revealed unexpected differences in the electrical conduction system of the genetically modified pig heart compared to a pig heart unmodified, based on preliminary research for will be presented at the 2022 Scientific Sessions of the American Heart Association. The meeting, held in-person in Chicago and virtually, November 5-7, 2022, is a premier global exchange on the latest scientific advances, research, and evidence-based clinical practice updates in cardiovascular sciences.

Xenotransplantation – the process of implanting an organ from one animal species to another – took a leap forward in January 2022, when a 57-year-old man with end-stage heart disease received the very first transplant of a genetically modified pig’s heart. The patient lived 61 days.

Researchers have been working on this new technique of pig-to-human transplantation for more than 30 years. If successful, harvesting genetically modified pig hearts, whose genes have been altered so they can be safely transplanted into humans, could one day become a reality.

“There are several potential challenges for transplanting a pig heart into a human. With any transplant, including this one, there is always a risk of rejection, a potential risk of infection, and a third is a rhythm. abnormal heart, and that’s where the electrocardiogram (ECG) comes in,” said Timm Dickfeld, MD, Ph.D., professor of medicine and director of electrophysiology research at the College of Medicine. University of Maryland at Baltimore “It is truly a novel finding that the ECG parameters of pig hearts after transplantation into humans were so different from the ECG parameters commonly found for native pig hearts.”

Post-transplant ECG monitoring of the heart is a way to assess the electrical conduction system after heart transplantation. A 12-lead ECG measures electrical conduction in 12 different electrical angles of the heart.

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

For this study, the transplant patient’s ECG data was collected typically once a day after the transplant. Previous research demonstrated that the ECG parameters of pig heart in pig body had short PR interval (50-120 milliseconds), short QRS (70-90 milliseconds), and short QT (260-380 milliseconds).

“In contrast, the first-ever ECG of a genetically engineered cardiac xenograft found a longer PR interval of 190 milliseconds, a QRS duration of 138 milliseconds, and a QT of 538 milliseconds, which is longer than one might expect. expect a pig’s heart in a pig’s body,” Dickfeld said.

“In a human heart, when these parameters elongate, it may indicate signs of electrical or myocardial disease,” he said. “Pig heart ECG parameters have been extended to what we see in a human heart and often the measurements have even extended beyond what we consider normal in a human heart.”

Additionally, continuous ECG measurements indicate that prolonged PR intervals remained stable post-transplant, averaging approximately 210 milliseconds. QRS duration remained prolonged with approximately 145 milliseconds, however, these were shortened later in the 61-day post-transplant period.

“The duration of the QRS can be prolonged when, for example, the muscle and the electrical system itself are diseased, and this is why it takes a long time for electricity to travel from one cell to another. and moves from one side of the heart to the other,” Dickfeld said. “In general, we would prefer that this QRS measurement not extend too long.”

Finally, the study revealed an increased QT duration of approximately 509 milliseconds on average with dynamic fluctuations. The lowest QT duration was observed on day 14. “In the human heart, QT duration is correlated with an increased risk of abnormal heart rhythms,” Dickfeld said. “In our patient, it was concerning that the QT interval measurement was prolonged. Although we observed some fluctuations, the QT measurement remained prolonged during the 61 days. »

The researchers believe these findings provide a foundation for future research to better understand the effects of xenotransplantation on the electrical system of the heart and to better prepare for future cases of xenotransplantation.

In 2020 (the most recent data available), the United States had the highest number of heart transplants with 3,658 transplants performed, according to the 2022 Heart Disease and Stroke Statistical Update from the American Heart Association. As of February 2021, 3,515 people were on the heart transplant waiting list and 49 people were on the heart and lung transplant waiting list, also according to the update.

“The ultimate goal is that if someone needs a heart, xenotransplantation may be an option,” Dickfeld said. “We need to make xenotransplantation safer and more feasible in these difficult areas: rejection, infection, pumping issues and certainly in the area of ​​electrical signals and abnormal heart rhythms.”

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

“It was a real milestone for research on xenotransplantation, the transplantation of organs from one species to another, in this case from pigs to humans. There have been a number of key steps that will be fundamental to the success of these operations largely centered on genetic manipulation to reduce organ rejection. Solving the problem of rejection may ultimately lead to the use of this method to help many patients with advanced heart failure,” said Paul J. Wang, MD, FAHA, who was not involved in the study. director of Stanford’s Cardiac Arrhythmia Service and a professor of medicine and bioengineering at Stanford University and editor of the Journal of the American Heart Association Circulation: arrhythmia and electrophysiology.

“It will be extremely interesting to understand the factors that affect the changes in the parameters observed by comparing pig-in-pig and pig-in-human values. We will want to look at factors such as how they reflect rejection and hemodynamic status,” Wang said. “Further analysis of the electrocardiogram, including ST-T wave abnormalities, can also provide unique insights.”

Co-authors are Calvin Kagan, MD; Richard Sandeep Amara, MD; Muhammad Haq, MD; Muhammad Mohiuddin, MBBS; Susie N. Hong-Zohlman, MD; Manjula Ananthram, MBBS; Charles C. Hong, MD, Ph.D.; Vincent Y. See, MD; Stephen Shorofsky, MD, Ph.D., and Bartley Griffith, MD Author disclosures are listed in the abstract.

The study authors did not report any outside sources of funding.

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Additional Resources:

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