A modified pig-to-human heart transplant had unexpected changes in the heart’s conduction system
Highlighted research results:
Electrocardiogram (ECG) measurements taken after the first pig-to-human heart transplant revealed significantly different electrical conduction characteristics compared to those seen in native pig hearts (pig heart transplanted into a pig).
Normal ECG measurements are usually shorter in pigs than in humans, but in January 2022, in a pig-to-human heart transplant, these ECG measurements were unexpectedly prolonged.
Embargoed until 4am CT/5am CT ET, Monday, October 31, 2022
(NewMediaWire) – October 31, 2022 Measurements of heart rhythm in the electrocardiograms of the first pig-to-human heart transplants have revealed unexpected differences in the electrical conduction system of a genetically modified pig heart compared to an unmodified pig heart, according to preliminary research to be presented at the Scientific Sessions of the American Association za srce 2022 The meeting, held in person in Chicago and virtually, November 5-7, 2022, is the premier global exchange of the latest scientific advances, research and evidence-based clinical practice updates in cardiovascular science.
Xenotransplantation, the process of transplanting organs from one animal species to another, has taken a leap forward January 2022, when a 57-year-old man with terminal heart disease received the first transplant of a genetically modified pig heart. The patient lived for 61 days.
Researchers have been working on this new pig-to-human transplant technique for more than 30 years. If successful, harvesting the hearts of genetically modified pigs, whose genes have been altered so that they can be safely transplanted into humans, could one day become a reality.
“There are several potential challenges to transplanting a pig heart into a human. With any transplant, including this one, there’s always a risk of rejection, a potential risk of infection, and the third is an abnormal heart rhythm, and that’s where the electrocardiogram (ECG) comes in,” Timm said. Dickfeld, MD, Ph.D., professor of medicine and director of electrophysiology research at the University of Maryland School of Medicine in Baltimore. “It is truly a novel finding that the ECG parameters of the pig heart after human transplantation were so different compared to the normal ECG parameters of the original pig hearts.”
Post-transplant ECG monitoring of the heart is one way to evaluate the electrical conduction system after heart transplantation. A 12-channel ECG measures electrical conduction in 12 different electrical angles of the heart.
Specifically, the researchers looked at two ECG measures: the PR interval/QRS complex and the QT interval. The PR interval and QRS complex measure the time it takes for electrical energy to travel from the upper to the lower chambers and through the lower chambers, thus pumping blood through the heart. The QT interval measures the time it takes the lower chambers of the heart to go through the full electrical cycle associated with a heartbeat.
For this study, the ECG data of the transplant patient was collected usually once a day after the transplant. Previous research has shown that the ECG parameters of the pig heart in the pig body have a short PR interval (50 to 120 milliseconds), a short QRS (70 to 90 milliseconds) and a short QT (260 to 380 milliseconds).
“In contrast, the first ECG of a genetically engineered heart xenograft revealed a longer PR interval of 190 milliseconds, a QRS duration of 138 milliseconds and a QT of 538 milliseconds, which is longer than would be expected from a pig heart in a pig body,” he said. Dickfeld.
“In the human heart, when these parameters become longer, it can indicate signs of electrical or myocardial disease,” he said. “The ECG parameters of the pig heart extended to what we see in the human heart, and often the measurements even exceeded what we consider normal in the human heart.”
In addition, continuous ECG measures showed that prolonged PR intervals remained stable after transplantation, averaging about 210 milliseconds. QRS duration remained prolonged at about 145 milliseconds, however, this shortened later during 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 so it takes a long time for the electricity to travel from cell to cell and travel from one side of the heart to the other,” Dickfeld said. “In general, we would prefer that this QRS measure not be prolonged too much.”
Finally, the study found a prolonged QT interval averaging about 509 milliseconds with dynamic fluctuations. The lowest QT duration was observed on day 14. “In the human heart, QT duration is associated with an increased risk of an abnormal heart rhythm,” Dickfeld said. “What is concerning about our patient is that the QT was prolonged. Although we saw some fluctuations, the QT remained prolonged for the entire 61 days.”
The researchers believe these findings provide the basis for future research to better understand the effects of xenotransplantation on the heart’s electrical system and to better prepare for future xenotransplantation cases.
In 2020 (the most recent data available), the United States recorded the highest number of heart transplants at 3,658, according to the American Heart Association Heart disease and stroke statistics update 2022. As of February 2021, there were 3,515 people on the heart transplant waiting list and 49 people on the heart-lung transplant waiting list, also according to the update.
“The ultimate goal is that if someone needs a heart, xenotransplantation can be an option,” Dickfeld said. “We need to make xenotransplantation safer and more feasible in these challenging areas: rejection, infection, pumping problems, and certainly in the area of abnormal electrical signals and heart rhythm.”
The main limitation is that this study is the first of its kind in a single patient. Future research will have a better foundation of knowledge to build on.
“This was a real turning point for xenotransplantation research, the transplantation of organs from one species to another, in this case from a pig to a human. There were a number of key steps that will be fundamental to the success of these operations mainly focused on genetic manipulations to reduce organ rejection. Solving of the rejection problem 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 professor of medicine and bioengineering at Stanford University and editor-in-chief of the American Heart Association journal Circulation: arrhythmia and electrophysiology.
“It will be extremely interesting to understand the factors that influence changes in observed parameters by comparing pig-in-pig values versus 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 may 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 Anantram, MBBS; Charles C. Hong, MD, Ph.D.; Vincent Y. See, MD; Stephen Shorofsky, MD, Ph.D., and Bartley Griffith, MD The authors’ findings are listed in the abstract.
The authors of the study reported no external sources of funding.
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